record_id,title,abstract,keywords,authors,year,date,doi,label_included,label_abstract_screening,duplicate_record_id
1,"Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II)","Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH = 6.5, the Mb binding selectivity follows the order Ag(I)=Cu(I)>Ni(II)=Zn(II)>Co(II)>>Mn(II)=Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)=Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. Graphical abstract .",,"McCabe, J. W.;Vangala, R.;Angel, L. A.",2017,Aug 30,https://dx.doi.org/10.1007/s13361-017-1778-9,0,0,
2,Characteristics and prevalence of Wilson's disease: A 2013 observational population-based study in France,"BACKGROUND AND AIMS: Only a few epidemiological studies on the incidence and prevalence of Wilson's disease (WD) have been performed to date, and the results vary widely according to the reports. The aim of the study was to investigate the prevalence, ambulatory care and treatments of patients with WD in France. METHODS: Among the 58 million general health scheme beneficiaries (86% of the French population), people managed for WD in 2013 were identified using hospitalisation diagnosis in 2011-2013 or specific long-term disease status with a 100% reimbursement for specific healthcare in 2013. Data were derived from the Sniiram (National Health Insurance Information System database). Prevalence by age and sex were calculated. RESULTS: In 2013, 906 prevalent cases were identified, yielding a crude prevalence of 1.5 cases per 100,000; 1.65 per 100,000 in males and 1.44 per 100,000 in females. This prevalence is comparable to that reported in other population-based studies in European countries and to a study using a similar method. Almost 40% of patients were treated by D-penicillamine and 14.3% were treated by zinc acetate. Trientine, delivered on a compassionate basis, was not available in the reimbursement database. In 2013, 1.3% of patients underwent liver transplantation and 4% had already undergone liver transplantation in previous years. Fifteen per cent of patients received antidepressants, a higher rate than in general population. CONCLUSIONS: This is the first French population-based epidemiological study of WD in a comprehensive population based on administrative data and constitutes an important step to understand the impact of WD and to study quality of care.",,"Poujois, A.;Woimant, F.;Samson, S.;Chaine, P.;Girardot-Tinant, N.;Tuppin, P.",2017,Jun 22,https://dx.doi.org/10.1016/j.clinre.2017.05.011,0,1,
3,Modality of treatment and potential outcome of Wilson disease in Taiwan: A population-based longitudinal study,"BACKGROUND/PURPOSE: This study aimed to investigate the epidemiology, the preference of medication, and the potential outcome of Wilson disease in Taiwan. We aimed to provide better therapeutic options for patients with Wilson disease based on the data generated from this study. METHODS: We utilized the National Health Insurance Research Database (NHIRD), which stores clinical records of nearly 99% of Taiwan's residents. The database used is a random sample of two-million out of 23-million beneficiaries in Taiwan's NHIRD in 2005. The integrated medical records of these two-million cases were collected from 2000 to 2011. Subjects of Wilson disease were identified as those with International Classification of Diseases, Ninth Revision (ICD-9) code 275.1 and the specific prescription drugs (including d-penicillamine, zinc, and trientine) in either outpatient clinic or inpatient records. RESULTS: During the study period, 66 cases of Wilson disease were identified. The male to female ratio was 1.75. The average prevalence rate was 1.81 per 100,000 and the average annual diagnosis rate was 0.22 per 100,000. The diagnosis was mostly established at 20-24 and 10-14 years of age, followed by 25-29 years. Fifty four of all subjects (81.8%) started the treatment with d-penicillamine, compared with zinc (12.1%) and trientine (6.1%). Among these 66 cases, 27 (40.9%) had liver cirrhosis and three (4.5%) underwent liver transplantation due to liver failure. CONCLUSIONS: d-penicillamine is still the most popular prescription of Wilson disease, followed by zinc monotherapy. Although chronic liver injury cannot be avoided, a favorable potential outcome is well demonstrated in this population-based study. Copyright © 2017. Published by Elsevier B.V.",,"Tai, C. S.;Wu, J. F.;Chen, H. L.;Hsu, H. Y.;Chang, M. H.;Ni, Y. H.",2017,Jun 01,https://dx.doi.org/10.1016/j.jfma.2017.05.008,1,1,
4,"The early history of manganese and the recognition of its neurotoxicity, 1837-1936","The history of the biomedical recognition manganese-caused neurotoxicity mirrors changing technologies as much as it does the ontology of parkinsonism. The initial 1837 report of manganese-induced neurologic injury was made by John Couper, a university-based physician in Scotland. He made clear that the outbreak occurred among workers at the Charles Tennant bleach manufactory in the environs of Glasgow. The relatively new technology of chlorine generation using manganese accounted for the novel exposure involved. At the time, this factory was the largest hypochlorite bleaching powder producer in the world. As the 19th century progressed, technological change in steel fabrication requiring higher manganese content greatly increased demand for the metal. Nonetheless, more than six decades elapsed before the next reports of manganese neurotoxicity emerged. Two unrelated outbreaks (both on Continental Europe) were reported within weeks of each other in 1901, one by von Jaksch and the other by Embden. All the cases were heavily exposed to manganese-containing dust. By the eve of the First World War, a total of 9 patients with manganese-caused neurologic illness had been reported in five separate Continental European publications. Meanwhile, new technology led to another exposure source. Magnetic separation techniques allowed the extraction of zinc from mixed ore also containing iron and manganese, leading to exploitation of a unique source of high manganese-content ore found in New Jersey. Not long after that technology's introduction, in 1912 Casamajor reported the first U.S. cases of manganism, detailing classic findings. Additional cases from the same cohort were reported a few years later, with continued exposure driven by First World War-driven demand for manganese to be used in armaments. The nosology of chronic manganese neurotoxicity remained in flux, with considerable emphasis on shared attributes with Wilson's disease, a syndrome only then recently described. A landmark 1924 primate study by Mella showed manganese-induced basal ganglion damage; human autopsy study data in the years following further supported the view that manganese toxicity represented a parkinsonian syndrome. As the 1937 centenary of Couper's first report approached, newer technologies (electric arc welding and battery making) were being linked to manganese-caused disease, even as mineral extraction was expanding as a global source of exposure. Copyright Published by Elsevier B.V.",,"Blanc, P. D.",2017,Apr 14,https://dx.doi.org/10.1016/j.neuro.2017.04.006,0,0,
5,Zinc monotherapy for young children with presymptomatic Wilson disease: a multicenter study in Japan,"BACKGROUND AND AIM: Few studies of zinc monotherapy for presymptomatic Wilson disease have focused on young children. We therefore evaluated long-term efficacy and safety of zinc monotherapy for such children, and established benchmarks for maintenance therapy. METHODS: We retrospectively and prospectively examined children under 10years old with presymptomatic Wilson disease who received zinc monotherapy from time of diagnosis at 12 participating pediatric centers in Japan. RESULTS: Twenty-four patients met entry criteria. Aspartate aminotransferase and alanine aminotransferase decreased significantly beginning 1month after initiation of treatment and usually remained under 50 U/L from 1 to 8years of treatment. Twenty four-hour urinary copper decreased significantly at 6months, and usually remained under 75micro g/day and between 1 and 3micro g/kg/day for the remainder of the study. All patients continued to take zinc, and none became symptomatic. In patients under 6years old who received 50mg/day of zinc as an initial dose, aspartate aminotransferase and alanine aminotransferase significantly decreased at 1month after initiation of treatment, as did gamma-glutamyltransferase and 24-hour urinary copper at 6months. CONCLUSIONS: To our knowledge, this is the first multicenter study of zinc monotherapy for young children with presymptomatic Wilson disease. Such monotherapy proved highly effective and safe. Maintaining normal transaminase values (or values under 50 U/L when normalization is difficult) and 24-hour urinary copper excretion between 1 and 3micro g/kg/day and under 75micro g/day is a reasonable goal. An initial dose of 50mg/day is appropriate for patients under 6years old. Copyright This article is protected by copyright. All rights reserved.",,"Eda, K.;Mizuochi, T.;Iwama, I.;Inui, A.;Etani, Y.;Araki, M.;Hara, S.;Kumagai, H.;Hagiwara, S. I.;Murayama, K.;Murakami, J.;Shimizu, N.;Kodama, H.;Yasuda, R.;Takaki, Y.;Yamashita, Y.",2018,Apr 28,https://dx.doi.org/10.1111/jgh.13812,0,0,
6,[Elastosis Perforans Serpiginosa and Wilson Disease: A Rare but Predictable Consequence of Long-term Therapy with D-Penicillamine],"Elastosis perfurans serpiginosa is a rare perforating dermatosis found primarily in adolescents and young adults, characterized by transepidermal elimination of abnormal elastic fibers. The only drug known capable of inducing elastosis perfurans serpiginosa is D-penicillamine. We report the case of a 52 year-old woman with keratotic papules arranged in an annular pattern with central clearing and centrifugal growth, located in the anterior cervical region. The patient was chronically treated with D-penicillamine for Wilson disease. Lesion biopsy showed transepidermal elimination of thickened, eosinophilic, branched, sawtooth-like elastic fibers. The clinical and pathological findings were consistent with elastosis perfurans serpiginosa secondary to D-penicillamine. It is estimated that elastosis perfurans serpiginosa occurs in 1% of patients treated with D-penicillamine. By blocking directly or indirectly the desmosine cross-links between elastin molecules, D-penicillamine leads to the synthesis of abnormal dermal and extracutaneous elastic fibers. Elastosis perfurans serpiginosa may be the first manifestation of a multisystemic degenerative process of elastic connective tissue.",,"Castro Pinho, A.;Cardoso, J. C.;Gouveia, M.;Oliveira, H.",2016,Mar,https://dx.doi.org/10.20344/amp.6749,0,0,
7,Combination Therapy Using Chelating Agent and Zinc for Wilson's Disease,"There is no clear international consensus regarding the optimal medication therapy for treating Wilson's disease (WD). This study systematically reviews the effectiveness of various medication therapies in common use, specifically focusing on preliminary findings concerning the combination of a chelating agent and zinc. A systematic PubMed search was executed to locate original studies on the effectiveness of commonly used medications for WD published between January 1989 and August 2014. The results were used to conduct a systematic review of studies on combination therapies. A total of 17 combination therapy studies involving 1056 patients were reviewed. These were analyzed in terms of data on effectiveness, adverse effects, and mortality. Results from a pooled analysis indicate that combination therapies for hepatic patients were significantly less effective than the same therapies for neurological manifestations (47.1 vs. 78.6 %; pooled relative risk ratio (RR): 0.63, 95 % confidence interval CI 0.43-0.94; p = 0.02). Data from a subgroup analysis show that the combination therapy of penicillamine plus zinc sulfate resulted in a significantly higher mortality rate compared to all other combination therapy types (16.3 vs. 4.7 %; RR: 3.51, 95 % CI 1.54-8.00; p < 0.001). The use of combination therapies involving zinc and a chelator should be carefully monitored with close clinical observations and frequent biochemical tests, especially for WD patients with hepatic manifestations.",,"Chen, J. C.;Chuang, C. H.;Wang, J. D.;Wang, C. W.",2015,,https://dx.doi.org/10.1007/s40846-015-0087-7,0,0,
8,Long-term effects of a combination of D-penicillamine and zinc salts in the treatment of Wilson's disease in children,"The aim of this study was to investigate the effectiveness of a high-dose zinc sulfate and low-dose D-penicillamine combination in the treatment of pediatric Wilson's disease (WD). A retropective chart review of 65 patients with WD was conducted. These patients received D-penicillamine (8-10 mg/kg/day) and zinc sulfate as the primary treatment. The pediatric dose of elemental zinc is 68-85 mg/day until 6 years of age, 85-136 mg/day until 8 years of age, 136-170 mg/day until 10 years of age and then 170 mg/day, in 3 divided doses 1 h before meals. After clinical and biochemical improvement or stabilization, zinc sulfate alone was administered as the maintenance therapy. Under treatment, the majority of patients (89.2%) had a favourable outcome and 3 patients succumbed due to poor therapy compliance. No penicillamine-induced neurological deterioration was noted and side-effects were observed in <11% of patients over the entire follow-up period. Benefical results on the liver and neurological symptoms were reported following extremely long-term treatment with a combination of low-dose D-penicillamine and high-dose zinc sulfate. Therefore, this regimen is an effective and safe treatment for children with WD.",,"Chang, H.;Xu, A.;Chen, Z.;Zhang, Y.;Tian, F.;Li, T.",2013,Apr,https://dx.doi.org/10.3892/etm.2013.971,0,0,
9,Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review,"Homeostasis of metal ions such as Zn(2+) is essential for proper brain function. Moreover, the list of psychiatric and neurodegenerative disorders involving a dysregulation of brain Zn(2+)-levels is long and steadily growing, including Parkinson's and Alzheimer's disease as well as schizophrenia, attention deficit and hyperactivity disorder, depression, amyotrophic lateral sclerosis, Down's syndrome, multiple sclerosis, Wilson's disease and Pick's disease. Furthermore, alterations in Zn(2+)-levels are seen in transient forebrain ischemia, seizures, traumatic brain injury and alcoholism. Thus, the possibility of altering Zn(2+)-levels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. Although the role of Zn(2+) in the brain has been extensively studied over the past decades, methods for controlled regulation and manipulation of Zn(2+) concentrations within the brain are still in their infancy. Since the use of dietary Zn(2+) supplementation and restriction has major limitations, new methods and alternative approaches are currently under investigation, such as the use of intracranial infusion of Zn(2+) chelators or nanoparticle technologies to elevate or decrease intracellular Zn(2+) levels. Therefore, this review briefly summarizes the role of Zn(2+) in psychiatric and neurodegenerative diseases and highlights key findings and impediments of brain Zn(2+)-level manipulation. Furthermore, some methods and compounds, such as metal ion chelation, redistribution and supplementation that are used to control brain Zn(2+)-levels in order to treat brain disorders are evaluated.",,"Grabrucker, A. M.;Rowan, M.;Garner, C. C.",2011,Sep,,0,0,
10,Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators,"Abnormal handling of copper is the cause of Wilson disease (WD), a rare disorder typified by increased levels in plasma copper not-bound to ceruloplasmin (nCp-Cu, also known as 'free' copper). In Alzheimer's disease (AD), meta-analyses show that copper decreases in brain but increases in serum, due to the nCp Cu component increase. Despite the similarities, a direct comparison of copper biological status in the two diseases has never been carried out. To fill this gap, we evaluated serum copper, ceruloplasmin, nCp-Cu and Cu:Cp in 385 CE and 336 healthy controls previously investigated that were compared with 9 newly diagnosed WD patients. We then assessed 24h copper urinary excretion in 24 WD patients under D-penicillamine (D-pen) treatment and in 35 healthy controls, and compared results with those of AD patients participating to a D-pen phase II clinical trial previously published. After adjusting for sex and age, serum nCp-Cu and Cu:Cp resulted higher in AD and in WD than in healthy controls (both p<0.001). While nCp-Cu was similar between AD and WD, Cu:Cp was higher in WD (p<0.016). 24h urinary copper excretion in AD patients (12.05mug/day) was higher than in healthy controls (4.82mug/day; p<0.001). 77.8% of the AD patients under D-pen treatment had a 24h urinary excretion higher than 200mug/day, suggestive of a failure of copper control. This study provides new insight into the pathophysiology of copper homeostasis in AD, showing a failure of copper control and the Cu:Cp ratio as an eligible marker.",,"Squitti, R.;Ghidoni, R.;Simonelli, I.;Ivanova, I. D.;Colabufo, N. A.;Zuin, M.;Benussi, L.;Binetti, G.;Cassetta, E.;Rongioletti, M.;Siotto, M.",2018,Jan,https://dx.doi.org/10.1016/j.jtemb.2017.11.005,0,0,
11,Insights into the management of Wilson's disease,"Wilson's disease is a rare, inherited autosomal recessive disease of copper metabolism, in which the causative gene, ATP7B, results in absent or reduced function of the ATP7B transporter important for biliary excretion of copper and incorporation of copper into caeruloplasmin. Affected patients accumulate excessive copper within the liver, brain and other tissues. A disease mainly of children, adolescents and young adults; clinical features vary from the asymptomatic state to chronic liver disease, acute liver failure, and neuropsychiatric manifestations. Diagnosis requires a high index of suspicion and is based on a combination of clinical signs, biochemical tests, hepatic copper content assay and mutation analysis of the ATP7B gene; to date, there are more than 500 mutations of ATP7B in patients with Wilson's disease. Early recognition and treatment can result in an excellent prognosis whereas untreated disease is almost always fatal. Drug therapies include chelating agents, such as penicillamine or trientine, and zinc salts. Liver transplantation is curative correcting the underlying pathophysiology and is traditionally indicated in acute liver failure or end-stage liver disease refractory to medical therapy. This review provides an overview of various aspects of Wilson's disease including molecular basis of the disease, clinical features, diagnostic and management strategies with their current limitations.",,"Kathawala, M.;Hirschfield, G. M.",2017,Nov,https://dx.doi.org/10.1177/1756283X17731520,0,0,
12,Bis-choline tetrathiomolybdate for Wilson's disease,,,"Houwen, R.",2017,Dec,https://dx.doi.org/10.1016/S2468-1253(17)30325-4,0,0,
13,"Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study","BACKGROUND: Wilson's disease is a genetic disorder in which copper accumulates in the liver, brain, and other tissues. Therapies are limited by efficacy, safety concerns, and multiple daily dosing. Bis-choline tetrathiomolybdate (WTX101) is an oral first-in-class copper-protein-binding molecule that targets hepatic intracellular copper and reduces plasma non-ceruloplasmin-bound copper (NCC) by forming tripartite complexes with albumin and increasing biliary copper excretion. We aimed to assess the efficacy and safety of WTX101 in the initial or early treatment of patients with Wilson's disease. METHODS: We did this open-label, phase 2 study at 11 hospitals in the USA and Europe. We enrolled patients (>=18 years) with Wilson's disease who were untreated or had received no more than 24 months of treatment with chelators or zinc, had a Leipzig score of 4 or more, and had NCC concentrations above the lower limit of the normal reference range (>=0.8 mumol/L). Eligible patients received WTX101 monotherapy at a starting dose of 15-60 mg/day on the basis of baseline NCC concentrations for the first 4-8 weeks, with response-guided individualised dosing for the remaining weeks up to week 24. Investigators, other hospital personnel, and patients were aware of the identity of the treatment. The primary endpoint was change in baseline NCC concentrations corrected for copper in tetrathiomolybdate-copper-albumin complexes (NCC<sub>corrected</sub>) at 24 weeks, with treatment success defined as achievement or maintenance of normalised NCC<sub>corrected</sub> (<=2.3 mumol/L [upper limit of normal]) or achievement of at least a 25% reduction in NCC<sub>corrected</sub> from baseline at 24 weeks. This study is registered with ClinicalTrials.gov, number NCT02273596. FINDINGS: Between Nov 24, 2014, and April 27, 2016, 28 patients were enrolled and received WTX101; 22 (79%) patients completed the study up to week 24. At 24 weeks, 20 (71%, 95% CI 51.3-86.8; p<0.0001) of 28 patients met the criteria for treatment success: 16 (57%) treated with WTX101 either achieved or maintained normalised NCC<sub>corrected</sub> concentrations and 4 (14%) had at least a 25% reduction from baseline NCC<sub>corrected</sub>. Mean NCC<sub>corrected</sub> was reduced by 72% from baseline to week 24 (least squares mean difference -2.4 mumol/L [SE 0.4], 95% CI -3.2 to -1.6; p<0.0001). No cases of paradoxical drug-related neurological worsening were recorded. Liver function was stable in all patients, although reversible increased concentrations of asymptomatic alanine or aspartate aminotransferase, or gamma-glutamyltransferase, without increased bilirubin, occurred in 11 (39%) of 28 patients who received at least 30 mg/day. 11 serious adverse events were reported in seven (25%) patients and included psychiatric disorders (six events in four patients), gait disturbance (one event), elevated liver aminotransferases (two events in two patients, one with agranulocytosis), and decline in neurological functioning (one event, likely due to natural disease progression although causality could not be ruled out). The seven serious adverse events categorised as psychiatric disorders and as gait disturbance were assessed as unlikely to be related to the study drug, whereas the remaining four events were possibly or probably related. INTERPRETATION: Our findings indicate that WTX101 might be a promising new therapeutic approach for Wilson's disease, with a unique mode of action. In view of its once-daily dose and favourable safety profile, WTX101 could improve the treatment of patients with this debilitating condition. FUNDING: Wilson Therapeutics AB.",,"Weiss, K. H.;Askari, F. K.;Czlonkowska, A.;Ferenci, P.;Bronstein, J. M.;Bega, D.;Ala, A.;Nicholl, D.;Flint, S.;Olsson, L.;Plitz, T.;Bjartmar, C.;Schilsky, M. L.",2017,Dec,https://dx.doi.org/10.1016/S2468-1253(17)30293-5,0,0,
14,Wilson's Disease,"Appropriate anticopper therapy for Wilson's disease is the critical element in halting progression of the disease and allowing patient recovery. Selection of the drug or drugs to use for a particular patient depends on the stage of the disease (ie, initial acutely ill patient versus chronic maintenance patient) and the type of presentation (ie, neurologic/psychiatric versus hepatic). I treat patients initially presenting with hepatic disease with a combination of zinc and trientine, those presenting with neurologic/psychiatric disease with tetrathiomolybdate, and those in the maintenance phase with zinc.",,"Brewer, G. J.",2000,May,,0,0,
15,Bioavailable Trace Metals in Neurological Diseases,"OPINION STATEMENT: Medical treatment in Wilson's disease includes chelators (D-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators' doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron.",,"Poujois, A.;Devedjian, J. C.;Moreau, C.;Devos, D.;Chaine, P.;Woimant, F.;Duce, J. A.",2016,Oct,https://dx.doi.org/10.1007/s11940-016-0426-1,0,0,
16,Early Onset of Wilson Disease: Diagnostic Challenges,"OBJECTIVES: The aim of the study was to analyze the clinical presentations, diagnosis, and treatment of patients ages <=5 years with early onset Wilson disease (WD). METHODS: Data from 143 pediatric patients with WD treated at our center between January 1996 and November 2015 were retrospectively analyzed. RESULTS: A review of the 143 pediatric patients with WD identified 21 (10 girls, 11 boys) with first symptoms or abnormal liver function test results at age <=5 years. The diagnosis of WD was confirmed in 8 patients younger than 5 years. At baseline the mean serum alanine aminotransferase level was 222 U/L and the mean serum aspartate aminotransferase level was 130 U/L. The mean serum ceruloplasmin concentration in 16 tested patients was <20 mg/dL. Of the 15 patients who underwent urinary copper excretion testing, 8 had levels between 40 and 100 mug/day, with only 4 having levels >100 mug/day. Liver copper quantification was >250 mug/g dry weight in 16 patients. The most common mutation was p.H1069Q, with compound heterozygosity in 5 patients and homozygosity in 9. Sixteen patients were treated with zinc salts and 5 with D-penicillamine. Both treatments were effective, with no serious side effects observed after 3 to 24 months. CONCLUSIONS: WD can present as early as 2 years of age. Because biochemical tests may be less sensitive in very young children, diagnoses may require a combination of tests. If molecular tests are inconclusive, liver copper content should be measured.",,"Wiernicka, A.;Dadalski, M.;Janczyk, W.;Kaminska, D.;Naorniakowska, M.;Husing-Kabar, A.;Schmidt, H.;Socha, P.",2017,Nov,https://dx.doi.org/10.1097/MPG.0000000000001700,0,1,
17,Wilson's disease: Prospective developments towards new therapies,"Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism, caused by mutations in the ATP7B gene. A clear demand for novel WD treatment strategies has emerged. Although therapies using zinc salts and copper chelators can effectively cure WD, these drugs exhibit limitations in a substantial pool of WD patients who develop intolerance and/or severe side effects. Several lines of research have indicated intriguing potential for novel strategies and targets for development of new therapies. Here, we review these new approaches, which comprise correction of ATP7B mutants and discovery of new compounds that circumvent ATP7B-deficiency, as well as cell and gene therapies. We also discuss whether and when these new therapeutic strategies will be translated into clinical use, according to the key requirements for clinical trials that remain to be met. Finally, we discuss the hope for the current rapidly developing research on molecular mechanisms underlying WD pathogenesis and for the related potential therapeutic targets to provide a solid foundation for the next generation of WD therapies that may lead to an effective, tolerable and safe cure.",,"Ranucci, G.;Polishchuck, R.;Iorio, R.",2017,Aug 14,https://dx.doi.org/10.3748/wjg.v23.i30.5451,0,0,
18,Dietary supplement implicated in fulminant hepatic failure in a well-controlled Wilson disease patient,"We encountered a patient with previously well-controlled Wilson disease who experienced fulminant hepatic failure with hemolytic anemia, possibly caused by the dietary supplement Health Proportion() (Jubilant Co., Ltd., Ehime, Japan). A 21-year-old woman was admitted to our hospital with marked liver dysfunction and severe hemolytic anemia. Free serum copper level was elevated at 101 mug/dl, and urinary copper excretion was extremely increased (25,600 mug/day). Plasma exchange and continuous hemodiafiltration were performed to remove serum copper and to treat the hemolytic anemia. However, liver function did not improve, and she underwent liver transplantation on 28th day after admission. Copper and iron contents in the resected liver were high at 851.9 mug and 551.7 mug/dry liver weight (g), respectively, despite the patient having regularly taken D-penicillamine since diagnosis and having a well-controlled copper level 1 year before her admission. Two months before admission, the patient had taken a dietary supplement made from soybeans for 1 month. This supplement was labeled as containing large amounts of copper and iron, and we assume that this caused fulminant hepatic failure with hemolytic crisis in this patient. It is important to be mindful of the micronutrient content of dietary supplements, especially for metabolic disorder patients.",,"Kawai, K.;Atarashi, Y.;Takahara, T.;Kudo, H.;Tajiri, K.;Tokimitsu, Y.;Nakayama, Y.;Hirano, K.;Yata, Y.;Minemura, M.;Yasumura, S.;Onishi, Y.;Tsukada, K.;Tsuneyama, K.;Takano, Y.;Sugiyama, T.",2009,Apr,https://dx.doi.org/10.1007/s12328-008-0056-6,0,0,
19,Chemosensitivity of U251 Cells to the Co-treatment of D-Penicillamine and Copper: Possible Implications on Wilson Disease Patients,"D-Penicillamine (PA), a copper chelator, and one of the recommended drugs for treatment of Wilson disease (WD) has been reported to worsen the symptoms of patients with neurologic presentations. However, the cause of this paradoxical response has not been fully elucidated and requires further investigations. Accordingly, we have studied the in vitro effect of Copper (Cu) and/or PA treatment on human glioblastoma U251 cells as an in vitro model of Cu cytotoxicity. Treatment of U251 cells with either Cu or PA exerted no significant effect on their morphology, viability or ROS level. In contrast, co-treatment with Cu-PA caused a decrease in viability, altered glutathione and ceruloplasmin expression coupled with marked increase in ROS; depolarization of mitochondrial membrane potential; and an increase in Sub G0 phase; along with alpha-Fodrin proteolysis. These findings along with the absence of LDH release in these assays, suggest that combined Cu-PA exposure induced apoptosis in U251 cells. In addition, pre-/or co-treatment with antioxidants showed a protective effect, with catalase being more effective than N-acetyl cysteine or trolox in restoring viability and reducing generated ROS levels. By comparison, a similar analysis using other cell lines showed that rat PC12 cells were resistant to Cu and/or PA treatment, while the neuroblastoma cell line SH-SY5Y was sensitive to either compound alone, resulting in decreased viability and increased ROS level. Taken together, this study shows that glioblastoma U251 cells provide a model for Cu-PA cytotoxicity mediated by H<sub>2</sub>O<sub>2</sub>. We postulate that PA oxidation in presence of Cu yields H<sub>2</sub>O<sub>2</sub> which in turn permeates the plasma membrane and induced apoptosis. However, other cell lines exhibited different responses to these treatments, potentially providing a model for cell type- specific cytotoxic responses in the nervous system. The sensitivity of different neural and glial cell types to Cu-PA treatment may therefore underlie the neurologic worsening occurring in some PA-treated WD patients. Our results also raise the possibility that the side effects of PA treatment might be reduced or prevented by administering antioxidants.",,"Katerji, M.;Barada, K.;Jomaa, M.;Kobeissy, F.;Makkawi, A. K.;Abou-Kheir, W.;Usta, J.",2017,,https://dx.doi.org/10.3389/fnmol.2017.00010,0,0,
20,Is a high serum copper concentration a risk factor for implantation failure?,"BACKGROUND: Copper-containing contraceptive devices may deposit copper ions in the endometrium, resulting in implantation failure. The deposition of copper ions in many organs has been reported in patients with untreated Wilson's disease. Since these patients sometimes exhibit subfertility and/or early pregnancy loss, copper ions were also considered to accumulate in the uterine endometrium. Wilson's disease patients treated with zinc successfully delivered babies because zinc interfered with the absorption of copper from the gastrointestinal tract. These findings led to the hypothesis that infertile patients with high serum copper concentrations may have implantation failure due to the excess accumulation of copper ions. The relationship between implantation (pregnancy) rates and serum copper concentrations has not yet been examined. The Japanese government recently stated that actual copper intake was higher among Japanese than needed. Therefore, the aim of the present study was to investigate whether serum copper concentrations are related to the implantation (pregnancy) rates of human embryos in vivo. METHODS: We included 269 patients (age <40 years old) who underwent vitrifying and warming single embryo transfer with a hormone replacement cycle using good blastocysts (3BB or more with Gardner's classification). Serum hCG, copper, and zinc concentrations were measured 16 days after the first date of progesterone replacement. We compared 96 women who were pregnant without miscarriage at 10 weeks of gestation (group P) and 173 women who were not pregnant (group NP). RESULTS: No significant differences were observed in age or BMI between the groups. Copper concentrations were significantly higher in group NP (average 193.2 mug/dL) than in group P (average 178.1 mug/dL). According to the area under the curve (AUC) on the receiver operating characteristic curve for the prediction of clinical pregnancy rates, the Cu/Zn ratio (AUC 0.64, 95% CI 0.54-0.71) was a better predictor than copper or zinc. When we set the cut-off as 1.59/1.60 for the Cu/Zn ratio, sensitivity, specificity, the positive predictive value, and negative predictive value were 0.98, 0.29, 0.71, and 0.88, respectively. CONCLUSIONS: Our single-center retrospective study suggests that high serum copper concentrations (high Cu/Zn ratio) are a risk factor for implantation failure.",,"Matsubayashi, H.;Kitaya, K.;Yamaguchi, K.;Nishiyama, R.;Takaya, Y.;Ishikawa, T.",2017,Aug 10,https://dx.doi.org/10.1186/s13104-017-2708-4,0,0,
21,WILSON'S DISEASE (A report of two cases),"Two cases of Wilson's disease are reported. First case presented with fulminant hepatic failure and had a fatal outcome. The second had an insiduous onset, neurological manifestations, and is progressing satisfactorily on zinc therapy. Problems in diagnosis and treatment are highlighted.",,"Kanitkar, M.;SN, J. OSHi;Roy, N. D.",1994,Jan,https://dx.doi.org/10.1016/S0377-1237(17)31042-0,0,0,
22,Inherited disorders of transition metal metabolism: an update,"Elements with a biological role include six trace transition metals: manganese, iron, cobalt, copper, zinc and molybdenum. Transition metals participate in group transfer reactions such as glycosylation and phosphorylation and those that can transfer an electron by alternating between two redox states such as iron (3+/2+) and copper (2+/1+) are also very important in biological redox reactions including the reduction of molecular oxygen and the transport of oxygen. However, these trace metals are also potentially toxic, generating reactive oxygen species through Fenton chemistry. Recently, a role of trace metals in host defence (""nutritional immunity"") has been recognized. The host can deprive the pathogen of a trace metal or poison it with a toxic concentration. Disorders leading to low concentrations of a trace metal can often be treated by supplementing that metal; disorders leading to excessively high concentrations can often be treated with chelating agents such as penicillamine and disodium calcium edetate. This update will address: i) the manganese/zinc transporters (because two new treatable disorders were described in 2016 - SLC39A8 deficiency and SLC39A14 deficiency); ii) copper transporter disorders because we need to improve the treatment of patients with neurological symptoms due to Wilson's disease; and iii) iron homeostasis because recent progress in research into the metabolism of iron and its regulation helps us better understand several inborn errors affecting these pathways.",,"Clayton, P. T.",2017,Jul,https://dx.doi.org/10.1007/s10545-017-0030-x,0,0,
23,Childhood Wilson Disease: Bangladesh Perspective,"Wilson's disease (WD) is an autosomal recessive disorder affecting copper metabolism causing copper induced damage to various organs. In children liver is commonly involved. Central nervous system, eyes, RBC, kidneys, brain and bones may also be affected. Aim of the study is to evaluate clinical & laboratory profile of Wilson's disease in children. This cross sectional descriptive study was conducted at the department of Paediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2011 to December, 2013. One hundred consecutive children of WD between 3 to 18 years of age were evaluated for clinical & biochemical profile. Mean age of studied children was 8.5+/-1.5 years. Male female ratio was 2:1. Ninety one percent patients were Muslim and nine percent Hindu. Consanguinity of marriage was found in 30% cases. Seven parents were first degree cousin. Family history of chronic liver disease was present in 15% of patients. Most (53%) cases of the hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Among 100 patients of WD, 69 children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic & neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of chronic liver disease were found in 18% patients. Commonest stigmata was thenar and hypothenar wasting (n=8). Keiser- Fleischser ring (K-F ring) was found in 76% of the total patients. K-F ring was present in 84% ( 58 out of 69) of the hepatic only Wilsonian patients and in 90% (18 out of 20) of all neurologic Wilsonian patients. Asymptomatic and psychiatric patient had no K-F ring. About 26% of the WD patients had Coombs negative hemolytic anemia in PBF. Most of the WD patients had altered liver function. Elevated serum transaminase was found in 85% of all cases, prolonged prothrombin time in 59% cases & low serum albumin in 53% cases. Seventy three percent patients had low serum ceruloplasmin, basal urinary copper of >100mugm/day was found in 81% cases and urinary copper following penicillamine challenge of >1200mugm/day was found in 92% cases. In 28 cases with hepatic presentation esophageal varices were identified by upper gastrointestinal endoscopy. WD patient with hepatic presentations were given zinc sulphate along with penicillamine. All patients with neurological manifestation as well as asymptomatic cases were maintained on zinc therapy. WD is a treatable metabolic cause of liver disease. Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD.",,"Rukunuzzaman, M.;Karim, A. B.;Nurullah, M.;Sultana, F.;Mazumder, M. W.;Rahman, M. A.;Billah, S. B.;Begum, F.;Oliullah, M.",2017,Apr,,0,0,
24,"Sip-1 mutations cause disturbances in the activity of NMDA- and AMPA-, but not kainate receptors of neurons in the cerebral cortex","Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b), Zeb2] is a transcription factor implicated in the genesis of Mowat-Wilson syndrome (MWS) in humans. MWS is a rare genetic autosomal dominant disease caused by a mutation in the Sip1 gene (aka Zeb2 or Zfhx1b) mapped to 2q22.3 locus. MWS affects 1 in every 50-100 newborns worldwide. It is characterized by mental retardation, small stature, typical facial abnormalities as well as disturbances in the development of the cardio-vascular and renal systems as well as some other organs. Sip1 mutations cause abnormal neurogenesis in the brain during development as well as susceptibility to epileptic seizures. In the current study we investigated the role of the Sip1 gene in the activity of NMDA-, AMPA- and KA- receptors. We showed that a particular Sip1 mutation in the mouse causes changes in the activity of both NMDA- and AMPA- receptors in the neocortical neurons in vitro. We demonstrate that neocortical neurons that have only one copy of Sip1 (heterozygous, Sip1<sup>fI/wt</sup>), are more sensitive to both NMDA- and AMPA- receptors agonists as compared to wild type neurons (Sip1<sup>wt/wt</sup>). This is reflected in higher amplitudes of agonist induced Ca<sup>2+</sup> signals as well as a lower half maximal effective concentration (IEC50). In contrast, neurons from homozygous Sip1 mice (Sip1<sup>fI/fI</sup>), demonstrate higher resistance to these respective receptor agonists. This is reflected in lower amplitudes of Ca<sup>2+</sup>-responses and so a higher concentration of receptor activators is required for activation. Copyright © 2017 Elsevier B.V. All rights reserved.",,"Turovskaya, M. V.;Babaev, A. A.;Zinchenko, V. P.;Epifanova, E. A.;Borisova, E. V.;Tarabykin, V. S.;Turovsky, E. A.",2017,May 22,https://dx.doi.org/10.1016/j.neulet.2017.04.048,0,0,
25,Novel perspectives on Wilson disease treatment,"Wilson disease is an autosomal-recessive copper overload disorder causing hepatic and neurologic symptoms. Commonly used medical therapy shows satisfactory results with regard to hepatic disease but only limited effects in neurologically affected patients. In recent years several new therapy options have been developed, showing promising results that might improve the management of Wilson disease in the near future. Optimization of treatment regimens depending on biochemical response pattern seems worthwhile, especially in the decoppering phase of therapy. The chelator tetrathiomolybdate (TTM) is a promising therapy option, currently under clinical investigation. TTM is a fast-acting and very potent chelator and appears to be associated with early neurologic deterioration after initiation of therapy to a lower extent than the drugs currently used. Treatment with nonchelating drugs characterized by alternative modes of action is under investigation, but restricted to animal or in vitro studies to date. This includes basic research studies demonstrating proof of principle for successful cell or gene therapy in Wilson disease in order to restore sufficient biliary copper excretion, even before the onset of disease. Copyright © 2017 Elsevier B.V. All rights reserved.",,"Rupp, C.;Stremmel, W.;Weiss, K. H.",2017,,https://dx.doi.org/10.1016/B978-0-444-63625-6.00019-7,0,0,
26,Symptomatic treatment of neurologic symptoms in Wilson disease,"Wilson disease (WD) is a potentially treatable neurodegenerative disorder. In the majority of cases, treatment with drugs that induce a negative copper balance (usually chelators or zinc salts) leads to improvements in liver function and neurologic signs. However, some patients show severe neurologic symptoms at diagnosis, such as tremor, dystonia, parkinsonism, and chorea. In this patient group, some neurologic deficits may persist despite adequate treatment, and further neurologic deterioration may be observed after treatment initiation. Such patients may require additional treatment to alleviate neurologic symptoms. Apart from general recommendations for WD anticopper treatment, there are currently no guidelines for managing neurologic symptoms in WD. The aim of this chapter is to summarize possible treatments of neurologic symptoms in WD based on the presently available medical literature. Copyright © 2017 Elsevier B.V. All rights reserved.",,"Litwin, T.;Dusek, P.;Czlonkowska, A.",2017,,https://dx.doi.org/10.1016/B978-0-444-63625-6.00018-5,0,0,
27,Wilson disease - currently used anticopper therapy,"Wilson disease (WD) is a genetic disorder of copper metabolism that can be treated successfully with pharmacologic treatment. Two groups of drugs are currently used: chelators (e.g., d-penicillamine and trientine), which increase urinary copper excretion, and zinc salts, which inhibit copper absorption in the digestive tract. The mechanisms of action lead to a negative copper balance, stopping pathologic accumulation of copper in the tissues and clearing affected organs of copper overload. Due to a lack of prospective clinical trials, the use of drugs depends mainly on center experience and the accessibility in different countries or regions. This chapter presents the different reports and recommendations regarding WD treatment. In addition to the different expert opinions on pharmacologic agents, there are a few axioms regarding WD treatment: treatment should start immediately after diagnosis, even in clinically presymptomatic cases; the patient should be treated for life, making compliance a key factor in treatment success; and the treatment should be monitored regularly via liver and hematologic tests, neurologic examination, and copper metabolism, modifying the treatment accordingly. Other drugs proposed for WD treatment (e.g., tetrathiomolybdate) are in clinical trials and lack current recommendations. Thus, only the currently available options for WD pharmacologic treatment are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.",,"Czlonkowska, A.;Litwin, T.",2017,,https://dx.doi.org/10.1016/B978-0-444-63625-6.00015-X,0,0,
28,Wilson disease in children,"Wilson disease (WD) is an inherited disorder mainly of hepatocellular copper disposition, due to dysfunction of the Wilson ATPase, a P<sub>1B</sub>-ATPase encoded by the gene ATP7B. In children, as in older age brackets, clinical disease is highly diverse. Although hepatic disease is the common presentation in children/adolescents, neurologic, psychiatric, and hematologic clinical presentations do occur. Very young children may have clinically evident liver disease due to WD. Early diagnosis, preferably when the child/adolescent is asymptomatic, is most likely to result in near-normal longevity with generally good health so long as the patient tolerates effective medication, is adherent to the lifelong treatment regimen, and has consistent access to the medication. Apart from a lively index of clinical suspicion on the part of physicians, biochemical tests including liver tests, serum ceruloplasmin, and basal 24-hour urinary copper excretion and genotype determination are key to diagnosis. Oral chelation treatment remains central to medical management, although zinc appears to be an attractive option for the presymptomatic child. Pediatric patients presenting with Wilsonian fulminant hepatic failure must be differentiated from those with decompensated cirrhosis, since the latter may respond to intensive medical interventions and not require liver transplantation. Recently identified WD-mimic disorders reveal important aspects of WD pathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.",,"Roberts, E. A.;Socha, P.",2017,,https://dx.doi.org/10.1016/B978-0-444-63625-6.00012-4,0,0,
29,Penicillamine-induced Elastosis Perforans Serpiginosa in Wilson Disease: Is Useful Switching to Zinc?,,,"Ranucci, G.;Di Dato, F.;Leone, F.;Vajro, P.;Spagnuolo, M. I.;Iorio, R.",2017,Mar,https://dx.doi.org/10.1097/MPG.0000000000000613,0,0,
30,"50 Years Ago in TheJournal ofPediatrics: Hepatolenticular Degeneration: The Comparative Effectiveness of D-Penicillamine, Potassium Sulfide, and Diethyldithiocarbamate as Decoppering Agents",,,"Hafberg, E. T.",2016,Jun,https://dx.doi.org/10.1016/j.jpeds.2015.12.040,0,0,
31,Single step synthesis of amine-functionalized mesoporous magnetite nanoparticles and their application for copper ions removal from aqueous solution,"Amine-functionalized mesoporous superparamagnetic Fe3O4 nanoparticles with an average size of 70nm have been synthesized using a single step solvothermal method by the introduction of triethylenetetramine (TETA), a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. The synthesized nanoparticles were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, nitrogen adsorption/desorption isotherm, vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). It is confirmed that the magnetic nanoparticles have been functionalized with TETA during the synthetic process, and the concentration of TETA is crucial for the formation of monodisperse mesoporous nanoparticles. The obtained single-crystal magnetic nanoparticles have a high magnetization, which enhances their response to external magnetic field and therefore should greatly facilitate the manipulation of the particles in practical uses. Reaction parameters affecting the formation of mesoporous structure were explored, and a possible formation mechanism involving templated aggregation and recrystallization processes was proposed. The capacity of the synthesized amine-functionalized Fe3O4 nanoparticles toward Cu(II) removal from aqueous solution was investigated. The adsorption rate of Cu(II) on amine-functionalized Fe3O4 nanoparticles followed a pseudo-second order kinetic model. The results of this study demonstrated that the amine-functionalized mesoporous superparamagnetic Fe3O4 nanoparticles could be used as an efficient adsorbent in water treatment and would also find potential application for Cu(II) removal in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.",,"Gao, J.;He, Y.;Zhao, X.;Ran, X.;Wu, Y.;Su, Y.;Dai, J.",2016,Nov 01,https://dx.doi.org/10.1016/j.jcis.2016.07.057,0,0,
32,Wilson's Disease with Systemic Lupus Erythematosus,"Case reports of Wilson's disease occurring in combination with SLE are rarely reported in literature. Drug induced lupus have been observed in patients taking D-penicillamine for Wilson's disease. Here we report a case from Coimbatore Medical College hospital, who presented with fever and neuropsychiatric symptoms as the initial manifestation and found to have both SLE and Wilson's disease on subsequent evaluation. Copyright © Journal of the Association of Physicians of India 2011.",,"Santhakumar, R.;Gayathri, K.;Ramalingam, P. K.;Manjunath, B. V.;Karuppusamy, N.;Vetriveeran, B.;Selvamani, S.;Vishnuram, P.;Muruganathan, A.;Natarajan, K.",2016,Apr,,0,0,
33,Rapid and reliable diagnosis of Wilson disease using X-ray fluorescence,"Wilson's disease (WD) is a rare autosomal recessive disease due to mutations of the gene encoding the copper-transporter ATP7B. The diagnosis is hampered by the variability of symptoms induced by copper accumulation, the inconstancy of the pathognomonic signs and the absence of a reliable diagnostic test. We investigated the diagnostic potential of X-ray fluorescence (XRF) that allows quantitative analysis of multiple elements. Studies were performed on animal models using Wistar rats (n=10) and Long Evans Cinnamon (LEC) rats (n=11), and on human samples including normal livers (n=10), alcohol cirrhosis (n=8), haemochromatosis (n=10), cholestasis (n=6) and WD (n=22). XRF experiments were first performed using synchrotron radiation to address the elemental composition at the cellular level. High-resolution mapping of tissue sections allowed measurement of the intensity and the distribution of copper, iron and zinc while preserving the morphology. Investigations were further conducted using a laboratory X-ray source for irradiating whole pieces of tissue. The sensitivity of XRF was highlighted by the discrimination of LEC rats from wild type even under a regimen using copper deficient food. XRF on whole formalin-fixed paraffin embedded needle biopsies allowed profiling of the elements in a few minutes. The intensity of copper related to iron and zinc significantly discriminated WD from other genetic or chronic liver diseases with 97.6% specificity and 100% sensitivity. This study established a definite diagnosis of Wilson's disease based on XRF. This rapid and versatile method can be easily implemented in a clinical setting.",,"Kascakova, S.;Kewish, C. M.;Rouziere, S.;Schmitt, F.;Sobesky, R.;Poupon, J.;Sandt, C.;Francou, B.;Somogyi, A.;Samuel, D.;Jacquemin, E.;Dubart-Kupperschmitt, A.;Nguyen, T. H.;Bazin, D.;Duclos-Vallee, J. C.;Guettier, C.;Le Naour, F.",2016,Jul,https://dx.doi.org/10.1002/cjp2.48,0,0,
34,The Challenges of Diagnosing and Following Wilson Disease in the Presence of Proteinuria,"The coexistence of Wilson disease with Alport syndrome has not previously been reported. The diagnosis of Wilson disease and its ongoing monitoring is challenging when associated with an underlying renal disease such as Alport syndrome. Proteinuria can lead to low ceruloplasmin since it is among serum proteins inappropriately filtered by the damaged glomerulus, and can also lead to increased urinary loss of heavy metals such as zinc and copper. Elevated transaminases may be attributed to dyslipidemia or drug induced hepatotoxicity. The accurate diagnosis of Wilson disease is essential for targeted therapy and improved prognosis. We describe a patient with a diagnosis of Alport syndrome who has had chronic elevation of transaminases eventually diagnosed with Wilson disease based on liver histology and genetics.",,"Khan, S.;Schilsky, M.;Silber, G.;Morgenstern, B.;Miloh, T.",2016,Jun,https://dx.doi.org/10.5223/pghn.2016.19.2.139,0,0,
35,Metallo-pathways to Alzheimer's disease: lessons from genetic disorders of copper trafficking,"Copper is an essential metal ion that provides catalytic function to numerous enzymes and also regulates neurotransmission and intracellular signaling. Conversely, a deficiency or excess of copper can cause chronic disease in humans. Menkes and Wilson disease are two rare heritable disorders of copper transport that are characterized by copper deficiency and copper overload, respectively. Changes to copper status are also a common feature of several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). In the case of AD, which is characterized by brain copper depletion, changes in the distribution of copper has been linked with various aspects of the disease process; protein aggregation, defective protein degradation, oxidative stress, inflammation and mitochondrial dysfunction. Although AD is a multifactorial disease that is likely caused by a breakdown in multiple cellular pathways, copper and other metal ions such as iron and zinc play a central role in many of these cellular processes. Pioneering work by researchers who have studied relatively rare copper transport diseases has shed light on potential metal ion related disease mechanisms in other forms of neurodegeneration such as AD.",,"Greenough, M. A.;Ramirez Munoz, A.;Bush, A. I.;Opazo, C. M.",2016,Sep 01,https://dx.doi.org/10.1039/c6mt00095a,0,0,
36,Clinical efficacy of combined sodium dimercaptopropanesulfonate and zinc treatment in neurological Wilson's disease with D-penicillamine treatment failure,"OBJECTIVES: There are limited pharmacological treatments for patients with neurological Wilson's disease (WD) and a history of copper-chelating treatment failure. METHODS: We retrospectively evaluated the clinical records of 38 patients with WD who were treated with sodium dimercaptopropanesulfonate (DMPS) and zinc (group 1) or zinc alone (group 2). All patients had a history of neurological deterioration during their previous treatment with D-penicillamine (DPA). RESULTS: Twenty-one patients were treated with intravenous DMPS for 4 weeks, followed by zinc gluconate for 6 months, and the treatment protocol was repeated twice. Relative to the baseline, repeated DMPS therapy and zinc maintenance therapy decreased neurological scores continuously (p < 0.01). Sixteen patients (76.2%) demonstrated neurological improvements after 1 year of therapy and four patients (19.0%) exhibited neurological deterioration at the follow-up session. In addition, 17 patients were treated with zinc monotherapy for 12 months. Two patients (11.8%) demonstrated neurological improvements and five patients (29.4%) exhibited neurological deterioration. Compared with the patients in group 2, a greater improvement ratio (p < 0.01) and lower deterioration ratio (p < 0.01) were observed in the patients in group 1 after 1 year of therapy. CONCLUSIONS: Our findings indicate that the safety and efficacy of combined treatment of DMPS and zinc is superior to those of zinc monotherapy in patients with neurological WD with a history of DPA treatment failure.",,"Chen, D.;Zhou, X.;Hou, H.;Feng, L.;Liu, J.;Liang, Y.;Lin, X.;Zhang, J.;Wu, C.;Liang, X.;Pei, Z.;Li, X.",2016,Jul,https://dx.doi.org/10.1177/1756285616641598,0,0,
37,Pregnancy outcome after chelation therapy in Wilson disease. Evaluation of the German Embryotox Database,"Continuation of treatment is recommended for pregnant women with Wilson disease. Therapy options include the copper chelating agents d-penicillamine and trientine. However, there are still uncertainties concerning a possible teratogenic risk. In this case series, we report on the outcome of 20 pregnancies with maternal chelator exposure at least during the first trimester. Of these 20 pregnancies documented by the German Embryotox Project, 14 were prospectively ascertained and 6 were retrospective. No major birth defects were observed. Three of the 14 prospective cases resulted in a spontaneous abortion, and one pregnancy was electively terminated. Our results do not support the hypothesis of teratogenicity based on earlier case reports of congenital anomalies. Therefore our study may contribute to reassure women needing chelation therapy during pregnancy. However, it must be taken into account that the sample size of this case series is too limited to make final conclusions on teratogenic effects. Copyright © 2016 Elsevier Inc. All rights reserved.",,"Dathe, K.;Beck, E.;Schaefer, C.",2016,Oct,https://dx.doi.org/10.1016/j.reprotox.2016.06.015,0,0,
38,A Patient With Primary Biliary Cirrhosis Accompanied by Wilson's Disease,"INTRODUCTION: Both primary biliary cirrhosis (PBC) and Wilson's disease (WD) can cause copper retention in the liver, which is an important factor for liver cellular damage. Copper chelation may preserve liver cell function. It is challenging to distinguish WD from copper accumulation in patients with PBC. There have been few case reports of PBC co-occurrence with WD. CASE PRESENTATION: Here we report a case of PBC with WD in a 55-year-old Chinese male. In addition to the typical pathological characteristics of PBC and a large number of copper depositions in the liver, the patient showed WD ATP7B gene mutations. CONCLUSIONS: Co-occurrence of PBC with WD is rare, which can cause diffusely intrahepatic copper deposition. Early liver biopsy and genetic testing are necessary for the diagnosis. The combination of ursodeoxycholic acid with zinc and sodium dimercaptopropane sulfonate is effective.",,"Zhao, S. X.;Zhang, Y. G.;Wang, R. Q.;Li, W. C.;Kong, L. B.;Kong, L.;Nan, Y. M.",2016,Feb,https://dx.doi.org/10.5812/hepatmon.29077,0,0,
39,Aberrance of Serum Zinc and Free Copper Level in Wilson Disease,,,"Iorio, R.;Ranucci, G.",2016,May,https://dx.doi.org/10.1097/MPG.0000000000001159,0,0,
40,Controversies and Variation in Diagnosing and Treating Children With Wilson Disease: Results of an International Survey,"OBJECTIVES: Variation in care is more common in settings in which evidence-based approaches are limited. The aims of the present study were to describe consensus and variability in approaches taken by pediatric hepatologists in the management of Wilson disease (WD) in children. METHOD: International case-centered, Internet-based survey of pediatric hepatologists. Survey cases were developed by consensus of the authors and were intended to identify variation in the care of children with WD. RESULTS: One hundred eleven of 253 clinicians responded (44%). Of these, 84% of North American and 41% of European participants used guidelines published in their respective region. Although consensus existed on the first-line diagnostic tools (serum ceruloplasmin and baseline 24-hour urinary copper excretion), survey participants did not agree on how much liver copper content was required for diagnosis: 57% considered >250 mug/g dry weight to be consistent with WD, whereas 25% considered >50 mug/g to be diagnostic. Overall, 50% of practitioners perform genetic testing in all suspected cases, and 81% perform genetic testing once they know the genotype of an index patient. For initial treatment of fulminant WD, 51% of participants chose chelation and 15% chose immediate transplantation; 47% chose listing for transplantation followed by monitoring using a disease-severity score, and then carrying out transplantation only when the score reached a critical cut-off. To treat mildly affected siblings of index patients, 43% of practitioners chose zinc. Most reported that they use chelation to treat patients with hepatic dysfunction; however, 29% of North American participants chose not to use D-penicillamine as primary therapy. CONCLUSIONS: From an international perspective, pediatric hepatologists vary in the approaches they use in the care for children with WD. Regional preferences and accessibility to treatments may generate variation. Unwarranted variation, however, may also contribute to differences in outcome and should be targeted to improve quality of care.",,"Sturm, E.;Piersma, F. E.;Tanner, M. S.;Socha, P.;Roberts, E. A.;Shneider, B. L.",2016,Jul,https://dx.doi.org/10.1097/MPG.0000000000001102,0,0,
41,Aberrance of Serum Zinc and Free Copper Level in Wilson Disease,,,"Sintusek, P.;Dhawan, A.",2016,May,https://dx.doi.org/10.1097/MPG.0000000000001084,0,0,
42,Wilson's disease: A review of what we have learned,"Wilson's disease (WD), which results from the defective ATP7B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.",,"Rodriguez-Castro, K. I.;Hevia-Urrutia, F. J.;Sturniolo, G. C.",2015,Dec 18,https://dx.doi.org/10.4254/wjh.v7.i29.2859,0,0,
43,Successful pregnancy outcome in a Korean patient with symptomatic Wilson's disease,"Wilson's disease is an inherited disease of copper metabolism leading to the toxic accumulation of copper, primarily in the liver and brain. Although the literature shows successful outcomes after proper treatment, pregnant patients with Wilson's disease still need close monitoring and management. Here, we report the case of a successful pregnancy in a Korean woman with Wilson's disease. A 33-year-old primigravid patient with Wilson's disease visited our antenatal clinic. Of her own volition, she had stopped her medication 2 years earlier. Oral zinc oxide therapy was started, and she was closely monitored throughout her pregnancy. She delivered a healthy female infant weighing 3.13 kg through a cesarean section. After delivery, the clinical course of both the mother and the baby were uneventful. We review crucial points in the treatment and the management dilemmas raised by the patient.",,"Lee, H. J.;Seong, W. J.;Hong, S. Y.;Bae, J. Y.",2015,Sep,https://dx.doi.org/10.5468/ogs.2015.58.5.409,0,0,
44,D-penicillamine Induced Degenerative Dermopathy,D-penicillamine interferes with elastin and collagen metabolism and produces several cutaneous and multi-systemic side-effects. We present two cases of Wilson's disease who on long-term penicillamine therapy developed drug-induced degenerative dermopathy manifesting as skin fragility over pressure sites and cutis laxa-like changes.,,"Khandpur, S.;Jain, N.;Singla, S.;Chatterjee, P.;Behari, M.",2015,Jul-Aug,https://dx.doi.org/10.4103/0019-5154.160498,0,0,
45,"Zebrafish in the sea of mineral (iron, zinc, and copper) metabolism","Iron, copper, zinc, and eight other minerals are classified as essential trace elements because they present in minute in vivo quantities and are essential for life. Because either excess or insufficient levels of trace elements can be detrimental to life (causing human diseases such as iron-deficiency anemia, hemochromatosis, Menkes syndrome and Wilson's disease), the endogenous levels of trace minerals must be tightly regulated. Many studies have demonstrated the existence of systems that maintain trace element homeostasis, and these systems are highly conserved in multiple species ranging from yeast to mice. As a model for studying trace mineral metabolism, the zebrafish is indispensable to researchers. Several large-scale mutagenesis screens have been performed in zebrafish, and these screens led to the identification of a series of metal transporters and the generation of several mutagenesis lines, providing an in-depth functional analysis at the system level. Moreover, because of their developmental advantages, zebrafish have also been used in mineral metabolism-related chemical screens and toxicology studies. Here, we systematically review the major findings of trace element homeostasis studies using the zebrafish model, with a focus on iron, zinc, copper, selenium, manganese, and iodine. We also provide a homology analysis of trace mineral transporters in fish, mice and humans. Finally, we discuss the evidence that zebrafish is an ideal experimental tool for uncovering novel mechanisms of trace mineral metabolism and for improving approaches to treat mineral imbalance-related diseases.",,"Zhao, L.;Xia, Z.;Wang, F.",2014,,https://dx.doi.org/10.3389/fphar.2014.00033,0,0,
46,A review and current perspective on Wilson disease,"Wilson disease is a rare, inherited autosomal recessive disease of copper metabolism and may be more common where consanguinity is prevalent. Much has been known about the disease after it was first described by Kinnier Wilson as 'progressive lenticular degeneration in 1912. Over 500 mutations of the ATP7B gene has been identified with no clear genotype to phenotype correlation. Loss of ATP7B function leads various grades of reduced biliary excretion of copper and reduced incorporation of copper into ceruloplasmin; accumulation and toxicity of copper in the liver, brain and other tissues results in liver toxicity and other myriad manifestations of the disease. The clinical features may vary from asymptomatic state to chronic liver disease, acute liver failure, neuropsychiatric manifestations and hemolytic anemia. Diagnosis is based on the combination of clinical sign's, biochemical features, histologic findings and mutation analysis of ATP7B gene. Subtle geographical differences exist with a disproportionate proportion of children presenting with acute liver failure. A high index of suspicion is needed for an early diagnosis. Ratios of biochemical indices for early diagnosis need validation across geographical regions and may not be particularly applicable in children. Better biomarkers or the need for tests for early detection of ALF persists. Drugs used in the treatment of Wilson disease include copper chelating agents such as d-Penicillamine, trientine and zinc salt. Untreated Wilson disease uniformly leads to death from liver disease or severe neurological disability. Early recognition and treatment has excellent prognosis. Liver transplantation is indicated in acute liver failure and end stage liver disease. Family screening in order to detect the disorder in the first-degree relatives is warranted. This review provides an overview of different aspects of Wilson disease including geographical differences in presentations and clinical management and the limitations of currently available tests.",,"Patil, M.;Sheth, K. A.;Krishnamurthy, A. C.;Devarbhavi, H.",2013,Dec,https://dx.doi.org/10.1016/j.jceh.2013.06.002,0,0,
47,Biometals in rare neurodegenerative disorders of childhood,"Copper, iron, and zinc are just three of the main biometals critical for correct functioning of the central nervous system (CNS). They have diverse roles in many functional processes including but not limited to enzyme catalysis, protein stabilization, and energy production. The range of metal concentrations within the body is tightly regulated and when the balance is perturbed, debilitating effects ensue. Homeostasis of brain biometals is mainly controlled by various metal transporters and metal sequestering proteins. The biological roles of biometals are vastly reviewed in the literature with a large focus on the connection to neurological conditions associated with ageing. Biometals are also implicated in a variety of debilitating inherited childhood disorders, some of which arise soon following birth or as the child progresses into early adulthood. This review acts to highlight what we know about biometals in childhood neurological disorders such as Wilson's disease (WD), Menkes disease (MD), neuronal ceroid lipofuscinoses (NCLs), and neurodegeneration with brain iron accumulation (NBIA). Also discussed are some of the animal models available to determine the pathological mechanisms in these childhood disorders, which we hope will aid in our understanding of the role of biometals in disease and in attaining possible therapeutics in the future.",,"Parker, S. J.;Koistinaho, J.;White, A. R.;Kanninen, K. M.",2013,,https://dx.doi.org/10.3389/fnagi.2013.00014,0,0,
48,D-penicillamine induced membranous glomerulonephritis in a child with Wilson's disease,,,"Theodoni, G.;Printza, N.;Karyda, S.;Pantzaki, A.;Papachristou, F.",2012,Jan,,0,0,
49,Refractory rickets due to Fanconi's Syndrome secondary to Wilson's disease,"Renal tubular disorders are an important cause of refractory rickets. Wilson's disease, an inherited disorder of copper metabolism has varied presentations. We present a case of refractory rickets due to Fanconi's syndrome attributable to Wilson's disease. An adolescent girl presented with pain in the hip and knee joints and a knock-knee deformity since six years. She had received multiple doses of cholecalciferol with little improvement. There was no history of seizures, polyuria, jaundice, intake of drugs, or similar complaints in the family. Examination revealed a severely short stature with widening of the wrist joint and genu valgum. Examination of the central nervous system (CNS) was normal. Skeletal radiographs showed features suggestive of rickets at the hip and knee joints. Routine biochemistry was normal, 25-hydroxyvitamin D [25(OH)D] was adequate (57.1 ng/dL), with normal corrected calcium (9.24 mg/dL), low phosphate (2.76 mg/dL), elevated bone-specific alkaline phosphatase, and normal renal functions. Twenty-four-hour urine revealed phosphaturia, kaliuresis, and glucosuria with normal blood sugars and aminoaciduria. Blood gas analysis revealed normal anion gap metabolic acidosis with a urine pH of 7. Ammonium chloride (NH4CL) challenge test revealed proximal tubular acidosis. A search for causes revealed Kayser-Fleischer rings. The diagnosis of Wilson's disease was confirmed by low serum ceruloplasmin levels (6.5 mg/dL; normal: 18-35 mg/dL) with high 24-hour urine copper levels (433 mcg; normal: 20-50 mcg). She was started on a replacement of alkali, phosphate, calcium, and vitamin D, with zinc acetate for Wilson's disease. Rickets as a presenting feature of Wilson's disease has been reported rarely. Recognition of this entity is important, as treatment of the primary condition may improve tubular function as well.",,"Selvan, C.;Thukral, A.;Chakraborthy, P. P.;Bhattacharya, R.;Roy, A.;Goswani, S.;Meher, D.;Ghosh, S.;Mukhopadhyay, S.;Chowdhury, S.",2012,Dec,https://dx.doi.org/10.4103/2230-8210.104107,0,0,
50,Mowat-Wilson syndrome: the first clinical and molecular report of an indonesian patient,"Mowat-Wilson syndrome (OMIM 235730) is a genetic condition characterized by moderate-to-severe intellectual disability, a recognizable facial phenotype, and multiple congenital anomalies. The striking facial phenotype in addition to other features such as severely impaired speech, hypotonia, microcephaly, short stature, seizures, corpus callosum agenesis, congenital heart defects, hypospadias, and Hirschsprung disease are particularly important clues for the initial clinical diagnosis. All molecularly confirmed cases with typical MWS have a heterozygous loss-of-function mutation in the zinc finger E-box protein 2 (ZEB2) gene, also called SIP1 (Smad-interacting protein 1) and ZFHX1B, suggesting that haploinsufficiency is the main pathological mechanism. Approximately 80% of mutations are nonsense and frameshift mutations (small insertions or deletions). About half of these mutations are located in exon eight. Here, we report the first Indonesian patient with Mowat-Wilson syndrome confirmed by molecular analysis.",,"Mundhofir, F. E.;Yntema, H. G.;van der Burgt, I.;Hamel, B. C.;Faradz, S. M.;van Bon, B. W.",2012,,https://dx.doi.org/10.1155/2012/949507,0,0,
51,Hypercalciuria and nephrocalcinosis as early feature of Wilson disease onset: description of a pediatric case and literature review,"BACKGROUND: Wilson's disease (WD) is a rare autosomal-recessive disorder characterized by a mutation in the ATP7B gene, located on chromosome 13, which encodes a protein involved in the metabolism of copper. CASE PRESENTATION: We described the case of an Indian male with a history of polydipsia and polyuria, related to hypercalciuria and consequent nephrocalcinosis. The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age. We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet. Renal involvement in Wilson's disease, characterizing by hypercalciuria, was firstly reported by Litin in 1959. CONCLUSION: Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.",,"Di Stefano, V.;Lionetti, E.;Rotolo, N.;La Rosa, M.;Leonardi, S.",2012,Aug,https://dx.doi.org/10.5812/hepatmon.6233,0,0,
52,Penicillamine neurotoxicity: an hypothesis,"Penicillamine, dimethyl cysteine, thiovaline, remains the drug of choice for the treatment of patience with Wilson disease. It is also of value in the treatment of cysteinuria and rheumatoid arthritis, it has also been suggested that it has value in the management of other rare diseases. It also has multiple toxicities. The majority of these can be explained as chemical toxicity, for instance its weak antipyridoxine action and its ability to interfere with lysyloxidea resulting in skin lesions. More important are its ability to induce immune reactions such as SLE, immune complex nephritis, the Ehlers Danlos syndrome and Goodpasture's syndrome. However the sudden increase in neurological signs which may occur in a small number of patients remains unexplained. The theory is proposed that this is due to lethal synthesis. In susceptible patients the-SH radical is liberated from penicillamine and will inhibit-SH dependent enzymes in the Krebs cycle leading to death in neurones. Other toxic metabolites may also be produced such as methyl mercaptan and ethyl mercaptan either of which could produce a similar metabolic block.",,"Walshe, J. M.",2011,,https://dx.doi.org/10.5402/2011/464572,0,0,
53,Paradigm shift in treatment of Alzheimer's disease: zinc therapy now a conscientious choice for care of individual patients,"Breakthrough in treatment of Alzheimer's disease with a shift from irrational dangerous chelation therapy to rational safe evidence based oral zinc therapy. Evidence based medicine: After synthesizing the best available clinical evidence I conclude that oral zinc therapy is a conscientious choice for treatment of free copper toxicosis in individual patients with Alzheimer's disease. Hypothesis 1: Age related free copper toxicosis is a causal factor in pathogenesis of Alzheimer's disease. There are 2 neurodegenerative diseases with abnormalities in copper metabolism: (a) the juvenile form with degeneration in the basal ganglia (Wilson's disease) and (b) the age related form with cortical neurodegeneration (Alzheimer's disease). Initially the hypothesis has been that neurodegeneration was caused by accumulation of copper in the brain but later experiences with treatment of Wilson's disease led to the conviction that free plasma copper is the toxic form of copper: it catalyzes amyloid formation thereby generating oxidative stress, free radicals and degeneration of cortical neurons. Hypothesis 2: Oral zinc therapy is an effective and safe treatment of free copper toxicosis in Alzheimer's disease. Proposed dosage: 50mg elementary zinc/day. Warning: Chelation therapy is irrational and dangerous in treatment of copper toxicosis in Alzheimer's disease.",,"Hoogenraad, T. U.",2011,,https://dx.doi.org/10.4061/2011/492686,0,0,
54,Anesthetic management of a pediatric patient with wilsons disease,"UNLABELLED: Wilsons disease, characterized by cirrhosis, extrapyramidal symptoms and Kayser-Fleischer corneal rings, is a rare hereditary disease of human copper metabolism. Clinical findings in Wilsons disease are complex and neurological symptoms such as tremor, dysarthria, rigid dystonia, seizures, psychiatric disorders, acute liver failure, chronic hepatitis or cirrhosis may develop. A 4-year-old male patient was operated for traumatic depressed skull fracture and intracerebral hematoma. He was diagnosed with Wilsons disease at the age of 2.5 years and treated with zinc sulphate and D-penicillamine. General anesthesia was induced with propofol, fentanyl, atracurium, and maintained with isoflurane, and oxygen. No complications were encountered during the operation or in the postoperative period. We concluded that general anesthesia can successfully be given to Wilsons disease patients using an anesthetic agent, the metabolism of which is least affected by the liver disease, one that induces least hepatic toxicity. By close follow-up of patients clinically and biochemically, it is possible to reduce the complication rates to a minimum. KEYWORDS: Wilson's Disease; Craniocerebral trauma; Thoracic injuries; General anesthesia; Surgery.",,"Baykal, M.;Karapolat, S.",2010,Mar 20,https://dx.doi.org/10.4021/jocmr2010.04.292w,0,0,
55,Wilson's disease masquerading as nonalcoholic steatohepatitis,"BACKGROUND: Wilson's disease is one of the most common hereditary causes of unclear hepatopathy. PATIENT #ENTITYSTARTX00026; METHOD: A 34-year old male patient with a history of hyperlipidemia was admitted with symptoms of abdominal pain and slight hematuria. Abnormal liver function tests, ultrasound reports and liver biopsy were suggestive of nonalcoholic steatohepatitis (NASH). The patient received preliminary treatment for NASH. However, on subsequent follow-up, NASH remained unresolved and liver histology showed fibrosis progression from fibrosis stage 1 to stage 3. RESULTS: Biochemical tests revealed that the levels of serum ceruloplasmin were decreased (7mg/dl) while the urinary excretion of copper was found to be increased (174.2 mug/day). Wilson's disease was confirmed by diagnostic mutation analysis involving Direct Sequencing. Heterogeneity in the patient's ATP7B gene confirmed Wilson's disease. Administration of D-penicillamine resulted in a decrease in fat deposition in the liver and no further progression in fibrosis after 10 months. CONCLUSION: Adult patient presenting NASH as first symptoms need to be examined for Wilson's disease and other metabolic conditions affecting the liver, prior to initiation of treatment.",,"Mahmood, S.;Inada, N.;Izumi, A.;Kawanaka, M.;Kobashi, H.;Yamada, G.",2009,Jul,,0,0,
56,Regression of Hypervascular Nodules in a Patient with Wilson's Disease Awaiting Liver Transplantation,"This paper describes the regressive course over one year of hypervascular nodules in a patient with Wilson's disease. CT revealed multiple, enhancing nodules (up to 3 cm in diameter) detected in the liver in the early arterial phase after the administration of intravenous contrast material. Most of these nodules became isodense in the portal venous phase. After one year of efficient therapy combining d-penicillamine and zinc acetate, most of the nodules had disappeared, while the liver contours had become more regular. To our knowledge, the regression of large hypervascular nodules has not previously been reported in patients with Wilson's disease.",,"Pissaia, A.;Gouya, H.;Scatton, O.;Conti, F.;Calmus, Y.",2009,,https://dx.doi.org/10.1155/2009/597371,0,0,
57,Sarcoidosis-induced pericarditis in a patient with portopulmonary hypertension: a case report,"Portopulmonary hypertension is a rare and severe complication of patients with cirrhosis. Sarcoidosis, a disease of unknown etiology, is also a cause of pulonary hypertension and right heart dysfunction. We report the case of a 51-year-old male patient, suffering from cirrhosis due to Wilson's disease, portal hypertension and pulmonary hypertension (PH), who developed severe pericarditis. Wilson's disease was diagnosed 8 years before his last admission to our hospital and was being successfully treated with D-penicillamine. PH was recognized 2 years before admission and being treated with bosentan. The patient complained for dyspnea at rest and the 2D echocardiogram revealed a significant amount of pericardial fluid. All other causes of acute pericarditis were excluded and his laboratory, imaging and histopathological investigation showed evidence of sarcoidosis. He underwent a therapy with corticosteroids (methylprednisolone) and his follow-up examination showed remarkable decrease of the levels of mean pulmonary artery pressure and pericardial fluid.",,"Giouleme, O.;Anagnostis, P.;Patsiaoura, K.;Vasiliadis, T.;Grammatikos, N.;Kakavas, N.;Mpoumponaris, A.;Eugenidis, N.;Basayannis, E.",2009,Aug 18,https://dx.doi.org/10.4076/1757-1626-2-8640,0,0,
58,Mania as a presenting symptom of Wilson's disease,"OBJECTIVE: Wilson's disease commonly presents with neurological or hepatic manifestations. When it presents with only psychiatric symptoms, or with extrapyramidal symptoms secondary to neuroleptic exposure, the diagnosis of underlying Wilson's disease may be missed. METHODS: An 18-year-old boy presented to the psychiatric clinic with a manic syndrome and high propensity for extrapyramidal symptoms to neuroleptic. Initial examination revealed splenomegaly and pancytopenia. Subsequent detection of Kayser-Fleischer ring and typical biochemical findings confirmed the diagnosis of Wilson's disease. RESULTS: While the psychiatric symptoms came under control with lithium carbonate, extrapyramidal symptoms continue to persist even after neuroleptic withdrawal. Pancytopenia thought to be due to hypersplenism persists, and patient has developed features of liver cirrhosis. Treatment with zinc and folic acid has been started, and the patient is under evaluation for treatment with penicillamine. CONCLUSION: The psychiatrist needs to recognize that Wilson's disease can uncommonly present with isolated psychiatric symptoms, including mania. Early and severe extrapyramidal symptoms secondary to neuroleptic exposure in an adolescent age group warrants a detailed evaluation to rule out underlying neuropsychiatric conditions.",,"Chand, P. K.;Murthy, P.",2006,Feb,https://dx.doi.org/10.1111/j.0924-2708.2006.00108.x,0,0,
59,Inherited metabolic liver disease,"PURPOSE OF REVIEW: The following section focuses on the disorders Wilson disease hemochromatosis and alpha-one antitrypsin deficiency, and the pivotal findings in publications this past year that furthers our understanding of the pathophysiology and treatment of these disorders. RECENT FINDINGS: For Wilson disease, there is new data regarding the structure and function of the responsible protein, ATP7B, and the importance of its proper cellular localization in hepatocytes, Other new information regarding the further use of zinc for initial treatment of this disease for asymptomatic patients, and the initial use of tetrathiomolybdate for neurologically affected patients will change our future approach to the treatment of patients with this disorder. New guidelines for diagnosis and treatment have also been set forth. New data has also advanced our understanding of hemochromatosis and iron overload disorders. Highlights this year include the discovery of a new gene involved in iron metabolism, hemojuvelin, and new data on the role of HFE mutations in the development of iron overload. Other data suggests that the altered regulation of the peptide hepcidin may play a pivotal role in the development of the iron overload phenotype in patients with hemochromatosis. For alpha-one antitrypsin, new information on the incidence of the disease in African based populations is being collected, and the role of autophagy in the pathogenesis of the disease continues to be explored. SUMMARY: Further understanding of these physiological alterations will help to better our understanding of the development of iron overload disorders, and may offer new avenues for therapeutic intervention.",,"Ala, A.;Schilsky, M. L.",2004,May,,0,0,
60,Comparative study of biliary trace elements and clinical phenotypes in Wilson's disease,"AIM: To further explore the etiological mechanism of Wilson's disease (WD) by comparing the changes of biliary trace elements and its clinical phenotype. METHODS: WD patients with different types and conditions (n = 20), non-WD patients with chronic liver damage (n = 22), and healthy volunteers (n = 10; used as controls) were studied. Biliary samples were taken by duodenal drainage. Atom absorption spectrophotometer was used to assay the copper and zinc content of each sample. RESULTS: In WD, the copper content and copper/zinc ratio of biliary juice were evidently lower than those of non-WD patients with chronic liver damage and of healthy controls (F = 14.76, 25.4; 14.92, 26.2 respectively; P < 0.01), while the biliary zinc level had no significant difference from the two non-WD control groups (P > 0.05). There were significant differences in biliary copper excretion among patients with different types and conditions (F = 3.75, P < 0.05; F = 6.20, P < 0.01). CONCLUSION: Copper excretion by liver and the biliary system decreases obviously in WD, which plays a key role in the phenotypic copper retention, and the biliary copper retention is closely related with the severity of hepatic injury and illness.",,"Ren, M. S.;Fan, Y. X.;Yang, R. M.;Han, Y. Z.;Wu, G. J.;Xin, Y. R.;Yu, L.",1997,Dec 15,https://dx.doi.org/10.3748/wjg.v3.i4.260,0,0,
61,"Adsorption of univalent and bivalent metal nitrates on hydrous lead dioxide Adsorption behaviour of potassium, cupric, zinc, cadmium and nitrate ions","The individual adsorption behaviour of potassium, cupric, zinc, cadmium and nitrate ions on hydrous lead dioxide (HLD) was investigated. HLD was found to be an amphoteric ion-exchanger with an equi-adsorption point in the vicinity of pH 4.6. For bivalent metal ions, the amount of adsorption increased with pH (at pH > 3) and there was almost 100% adsorption at pH > 6. Both the adsorption capacity and the adsorption affinity on HLD were in the order copper(II) > zinc(II) > cadmium(II).",,"Kawano, H.;Nakai, Y.;Matsuda, T.;Nagai, T.",1986,Feb,,0,0,
62,Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase,"Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection.<b>IMPORTANCE</b> Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.","*Antiviral Agents/pd [Pharmacology];Carcinoma, Hepatocellular/en [Enzymology];Carcinoma, Hepatocellular/pa [Pathology];Carcinoma, Hepatocellular/vi [Virology];*Hepatitis E/dt [Drug Therapy];Hepatitis E/vi [Virology];*Hepatitis E virus/de [Drug Effects];Hepatitis E virus/en [Enzymology];Hepatitis E virus/ge [Genetics];Humans;Liver Neoplasms/en [Enzymology];Liver Neoplasms/pa [Pathology];Liver Neoplasms/vi [Virology];*RNA Replicase/ai [Antagonists & Inhibitors];RNA, Viral/ge [Genetics];Tumor Cells, Cultured;*Virus Replication/de [Drug Effects];*Zinc Compounds/pd [Pharmacology];0 (Antiviral Agents);0 (RNA, Viral);0 (Zinc Compounds);EC 2-7-7-48 (RNA Replicase)","Kaushik, N.;Subramani, C.;Anang, S.;Muthumohan, R.;Shalimar;Nayak, B.;Ranjith-Kumar, C. T.;Surjit, M.",2017,Nov 01,https://dx.doi.org/10.1128/JVI.00754-17,0,0,
63,"The effects of arbuscular mycorrhizal fungi on glomalin-related soil protein distribution, aggregate stability and their relationships with soil properties at different soil depths in lead-zinc contaminated area","Glomalin-related soil protein (GRSP), a widespread glycoprotein produced by arbuscular mycorrhizal fungi (AMF), is crucial for ecosystem functioning and ecological restoration. In the present study, an investigation was conducted to comprehensively analyze the effects of heavy metal (HM) contamination on AMF status, soil properties, aggregate distribution and stability, and their correlations at different soil depths (0-10, 10-20, 20-30, 30-40 cm). Our results showed that the mycorrhizal colonization (MC), hyphal length density (HLD), GRSP, soil organic matter (SOM) and soil organic carbon (SOC) were significantly inhibited by Pb compared to Zn at 0-20 cm soil depth, indicating that HM had significant inhibitory effects on AMF growth and soil properties, and that Pb exhibited greater toxicity than Zn at shallow layer of soil. Both the proportion of soil large macroaggregates (>2000 mum) and mean weight diameter (MWD) were positively correlated with GRSP, SOM and SOC at 0-20 cm soil depth (P < 0.05), proving the important contributions of GRSP, SOM and SOC for binding soil particles together into large macroaggregates and improving aggregate stability. Furthermore, MC and HLD had significantly positive correlation with GRSP, SOM and SOC, suggesting that AMF played an essential role in GRSP, SOM and SOC accumulation and subsequently influencing aggregate formation and particle-size distribution in HM polluted soils. Our study highlighted that the introduction of indigenous plant associated with AMF might be a successful biotechnological tool to assist the recovery of HM polluted soils, and that proper management practices should be developed to guarantee maximum benefits from plant-AMF symbiosis during ecological restoration.","Carbon/an [Analysis];Chlorophyll/me [Metabolism];*Fungal Proteins/me [Metabolism];*Fungi/me [Metabolism];*Glycoproteins/me [Metabolism];*Lead/an [Analysis];Lead/me [Metabolism];Mycorrhizae/gd [Growth & Development];*Mycorrhizae/me [Metabolism];*Soil/ch [Chemistry];Soil Microbiology;*Soil Pollutants/an [Analysis];Soil Pollutants/me [Metabolism];Spectrophotometry, Atomic;*Zinc/an [Analysis];Zinc/me [Metabolism];0 (Fungal Proteins);0 (Glycoproteins);0 (Soil);0 (Soil Pollutants);0 (glomalin, Mycorrhizae);1406-65-1 (Chlorophyll);2P299V784P (Lead);7440-44-0 (Carbon);J41CSQ7QDS (Zinc)","Yang, Y.;He, C.;Huang, L.;Ban, Y.;Tang, M.",2017,,https://dx.doi.org/10.1371/journal.pone.0182264,0,0,
64,Wilson's disease: the 60th anniversary of Walshe's article on treatment with penicillamine,"This historical review describes Professor Walshe's seminal contribution to the treatment of Wilson's disease on the 60th anniversary of his pioneering article on penicillamine, the first effective treatment for the condition.","*Biomedical Research/hi [History];Boston;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/hi [History];History, 20th Century;*Penicillamine/hi [History];*Periodicals as Topic/hi [History];United Kingdom;GNN1DV99GX (Penicillamine)","Teive, H. A.;Barbosa, E. R.;Lees, A. J.",2017,Jan,https://dx.doi.org/10.1590/0004-282X20160166,0,0,
65,Wilson Disease: Epigenetic effects of choline supplementation on phenotype and clinical course in a mouse model,"Wilson disease (WD), a genetic disorder affecting copper transport, is characterized by hepatic and neurological manifestations with variable and often unpredictable presentation. Global DNA methylation in liver was previously modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j offspring could be modified by maternal methyl supplementation during pregnancy. In an initial experiment, female tx-j mice or wild type mice were fed control or choline-supplemented diets 2 weeks prior to mating through embryonic day 17. Transcriptomic analysis (RNA-seq) on embryonic livers revealed tx-j-specific differences in genes related to oxidative phosphorylation, mitochondrial dysfunction, and the neurological disorders Huntington's disease and Alzheimer disease. Maternal choline supplementation restored the transcript levels of a subset of genes to wild type levels. In a separate experiment, a group of tx-j offspring continued to receive choline-supplemented or control diets, with or without the copper chelator penicillamine (PCA) for 12 weeks until 24 weeks of age. Combined choline supplementation and PCA treatment of 24-week-old tx-j mice was associated with increased liver transcript levels of methionine metabolism and oxidative phosphorylation-related genes. Sex differences in gene expression within each treatment group were also observed. These results demonstrate that the transcriptional changes in oxidative phosphorylation and methionine metabolism genes in WD that originate during fetal life are, in part, prevented by prenatal maternal choline supplementation, a finding with potential relevance to preventive treatments of WD.","Animals;Choline/ad [Administration & Dosage];Choline/me [Metabolism];Copper/me [Metabolism];*DNA Methylation/ge [Genetics];Dietary Supplements;Disease Models, Animal;*Epigenomics;Female;Gene Expression Regulation/de [Drug Effects];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/me [Metabolism];Liver/pa [Pathology];Methionine/me [Metabolism];Mice;Oxidative Phosphorylation/de [Drug Effects];Penicillamine/ad [Administration & Dosage];Pregnancy;*Transcriptome/ge [Genetics];789U1901C5 (Copper);AE28F7PNPL (Methionine);GNN1DV99GX (Penicillamine);N91BDP6H0X (Choline)","Medici, V.;Kieffer, D. A.;Shibata, N. M.;Chima, H.;Kim, K.;Canovas, A.;Medrano, J. F.;Islas-Trejo, A. D.;Kharbanda, K. K.;Olson, K.;Su, R. J.;Islam, M. S.;Syed, R.;Keen, C. L.;Miller, A. Y.;Rutledge, J. C.;Halsted, C. H.;LaSalle, J. M.",2016,Nov,https://dx.doi.org/10.1080/15592294.2016.1231289,0,0,
66,Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease,"Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease. Copyright © 2016 Elsevier Inc. All rights reserved.","Adult;Apoptosis/de [Drug Effects];Caspase 3/me [Metabolism];Cell Line, Tumor;Cell Proliferation/de [Drug Effects];*Copper/to [Toxicity];DNA Damage;*Endoplasmic Reticulum Stress/de [Drug Effects];Female;Fluorescent Antibody Technique;HEK293 Cells;Hepatocytes/de [Drug Effects];*Hepatocytes/pa [Pathology];*Hepatolenticular Degeneration/pa [Pathology];Humans;Hydrogen Peroxide/me [Metabolism];Immunoblotting;Ki-67 Antigen/me [Metabolism];Male;Middle Aged;Oxidative Stress/de [Drug Effects];Proteasome Inhibitors/pd [Pharmacology];Zinc Acetate/pd [Pharmacology];0 (Ki-67 Antigen);0 (Proteasome Inhibitors);789U1901C5 (Copper);BBX060AN9V (Hydrogen Peroxide);EC 3-4-22 (Caspase 3);FM5526K07A (Zinc Acetate)","Oe, S.;Miyagawa, K.;Honma, Y.;Harada, M.",2016,Sep 10,https://dx.doi.org/10.1016/j.yexcr.2016.08.003,0,0,
67,Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation,"Polyamine metabolism is an attractive anticancer drug target, since polyamines are absolutely required for cellular proliferation, and increased levels of polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) are associated with cancer. Triethylenetetramine (TETA) is a charge-deficient isosteric analogue of the polyamine spermidine (Spd) and a Cu(II)-chelating compound used for the treatment of Wilson's disease, and it has been implicated as a potential anticancer therapeutic drug. In the present study, we studied the effects of TETA in comparison with two other Cu(II)-chelators, D-penicillamine (PA) and tetrathiomolybdate (TTM), on polyamine metabolism in DU145 prostate carcinoma, MCF-7 breast carcinoma and JEG-3 choriocarcinoma cells. TETA induced antizyme, down-regulated ODC and inhibited [(14)C] Spd uptake. Moreover, it completely prevented alpha-difluoromethylornithine (DFMO)-induced increase in [(14)C] Spd uptake, and inhibited [(14)C] putrescine (Put) uptake and ODC activity in vivo Seven-day treatment of DU145 cells with TETA caused growth cessation by reducing intracellular polyamine levels and suppressing the formation of hypusinated eukaryotic translation initiation factor 5A (eIF5A). TETA or its N-acetylated metabolites also inhibited spermine (Spm), diamine and semicarbazide-sensitive amine oxidases and decreased the level of intracellular reactive oxygen species. Moreover, TETA inhibited the utilization of Put as energy source via the tricarboxylic acid (TCA) cycle, as indicated by decreased production of (14)CO2 from [(14)C] Put. These results indicate that TETA attacks multiple proven anticancer drug targets not attributed to copper chelation, which warrants further studies to reveal its potential in cancer chemoprevention and cure. Copyright © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.","Amine Oxidase (Copper-Containing);Cell Line, Tumor;*Cell Proliferation/de [Drug Effects];Eflornithine/me [Metabolism];*Energy Metabolism/de [Drug Effects];Female;Humans;MCF-7 Cells;Male;Molybdenum/pd [Pharmacology];Penicillamine/me [Metabolism];*Polyamines/me [Metabolism];Putrescine/me [Metabolism];Reactive Oxygen Species/me [Metabolism];Spermine/me [Metabolism];*Trientine/pd [Pharmacology];0 (Polyamines);0 (Reactive Oxygen Species);2FZ7Y3VOQX (Spermine);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-4-3-21 (Amine Oxidase (Copper-Containing));GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine);V10TVZ52E4 (Putrescine);ZQN1G5V6SR (Eflornithine)","Hyvonen, M. T.;Ucal, S.;Pasanen, M.;Peraniemi, S.;Weisell, J.;Khomutov, M.;Khomutov, A. R.;Vepsalainen, J.;Alhonen, L.;Keinanen, T. A.",2016,May 15,https://dx.doi.org/10.1042/BCJ20160134,0,0,
68,Solid state stability and solubility of triethylenetetramine dihydrochloride,"The API triethylenetetramine dihydrochloride used as an alternative treatment of Wilson's disease is sensitive to water and it exhibits polymorphism. As this may become an issue for the drug formulation, the physical stability has been studied by differential scanning calorimetry, high-pressure thermal analysis, dynamic vapor sorption, and X-ray diffraction as a function of temperature. In addition, high-pressure liquid chromatography and mass spectrometry have been used to study the purity and chemical stability of the API. A pressure-temperature phase diagram of the pure compound has been constructed and it can be concluded that form II is monotropic in relation to form I, which is the only stable solid. The solubilities of the different solid forms have been determined with the help of a temperature - composition phase diagram. The API is very soluble, at 20degree C about 10% of the saturated solution with respect to the dihydrate consists of API and the solubility of the pure form I is twice as high. Moreover, it has been shown that at 20degreeC, a relative humidity above 40% induces the formation of the dihydrate and at 70% a saturated solution appears. At higher temperatures, the formation of the dihydrate appears at lower relative humidity values. A clear link has been established between the API's chemical stability, its physical stability and the relative humidity in the air. Humidity levels above 40% are detrimental to the quality of the API. Copyright © 2016 Elsevier B.V. All rights reserved.","Calorimetry, Differential Scanning/mt [Methods];Drug Stability;Magnetic Resonance Spectroscopy/mt [Methods];Solubility;*Trientine/ch [Chemistry];*Trientine/me [Metabolism];SJ76Y07H5F (Trientine)","Henriet, T.;Gana, I.;Ghaddar, C.;Barrio, M.;Cartigny, Y.;Yagoubi, N.;Do, B.;Tamarit, J. L.;Rietveld, I. B.",2016,Sep 10,https://dx.doi.org/10.1016/j.ijpharm.2016.06.140,0,0,
69,A clinical study of bone mesenchymal stem cells for the treatment of hepatic fibrosis induced by hepatolenticular degeneration,"The efficacy of bone marrow mesenchymal stem cell (BMSC) on liver fibrosis in animal has been proven, but a few studies have been made in human body and few such researches in China. This study was designed to investigate the effect of BMSC treatment on hepatic fibrosis induced by hepatolenticular degeneration and the influence on serological indicators. Sixty patients with liver fibrosis induced by hepatolenticular degeneration were randomly divided into two groups, a penicillamine group and a BMSCs plus penicillamine group, with 30 patients in each. The therapeutic effects on hepatic fibrosis, liver function, and serological indicators were recorded before and after the treatment, and the data were compared. After treatment, serum levels of HA, PCIII, LN, CIV, TIMP-1, and MMP-1 were reduced in both groups (P < 0.05). However, cytokine levels in the BMSCs plus penicillamine group were significantly lower than those in the penicillamine group (P < 0.05). Combination therapy with BMSCs and penicillamine had a significant positive effect on liver fibrosis induced by hepatolenticular degeneration.","Adult;Biomarkers/bl [Blood];Case-Control Studies;Cells, Cultured;Chelating Agents/ad [Administration & Dosage];Combined Modality Therapy;Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver/me [Metabolism];Liver/pa [Pathology];Liver Cirrhosis/bl [Blood];Liver Cirrhosis/et [Etiology];*Liver Cirrhosis/th [Therapy];Male;*Mesenchymal Stem Cell Transplantation;Mesenchymal Stromal Cells/ph [Physiology];Penicillamine/ad [Administration & Dosage];Transforming Growth Factor beta1/bl [Blood];Treatment Outcome;Tumor Necrosis Factor-alpha/bl [Blood];Young Adult;0 (Biomarkers);0 (Chelating Agents);0 (TGFB1 protein, human);0 (TNF protein, human);0 (Transforming Growth Factor beta1);0 (Tumor Necrosis Factor-alpha);GNN1DV99GX (Penicillamine)","Zhang, D.",2017,Mar 15,https://dx.doi.org/10.4238/gmr16019352,0,0,
70,Early cirrhosis in a young female with protein C deficiency: An extremely unusual case report with review,"Protein C deficiency is a well recognized risk factor for development of venous thromboembolism but has never been reported to be associated with development of liver cirrhosis .We report a case of a 26 years old female who presented with multiple thrombosis involving superior mesenteric vein ,main portal vein and multiple cerebral veins. Liver biopsy done was reported as cirrhosis possibly due to Wilson's disease. However no improvement was seen with D penicillamine and patient's condition detiorated. Further, work up of patient revealed absence of Protein C levels in the plasma. So finally the case was diagnosed as Cirrhosis liver with Protein C deficiency as the likely etiology. We conclude that Protein C deficiency should be investigated in patients with cirrhosis with thrombotic lesions of unknown etiology.","Adult;Biopsy;Female;Histocytochemistry;Humans;Liver/dg [Diagnostic Imaging];*Liver/pa [Pathology];*Liver Cirrhosis/et [Etiology];*Liver Cirrhosis/pa [Pathology];Microscopy;Plasma/ch [Chemistry];*Protein C Deficiency/co [Complications];*Protein C Deficiency/di [Diagnosis];Radiography, Abdominal;Tomography, X-Ray Computed","Bansal, N.;Bihari, C.",2016,Jul-Sep,https://dx.doi.org/10.4103/0377-4929.188119,0,0,
71,Letting post-marketing bridge the evidence gap: the case of orphan drugs,,"*Adrenal Cortex Neoplasms/dt [Drug Therapy];*Adrenocortical Carcinoma/dt [Drug Therapy];Anti-Inflammatory Agents, Non-Steroidal/tu [Therapeutic Use];Antineoplastic Agents/tu [Therapeutic Use];Antineoplastic Agents, Hormonal/tu [Therapeutic Use];Barrett Esophagus/dt [Drug Therapy];Cladribine/tu [Therapeutic Use];Dihematoporphyrin Ether/tu [Therapeutic Use];Ductus Arteriosus, Patent/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Ibuprofen/tu [Therapeutic Use];Leukemia, Hairy Cell/dt [Drug Therapy];Mitotane/tu [Therapeutic Use];*Orphan Drug Production;Platelet Aggregation Inhibitors/tu [Therapeutic Use];*Product Surveillance, Postmarketing;Quinazolines/tu [Therapeutic Use];Thrombocythemia, Essential/dt [Drug Therapy];Zinc Acetate/tu [Therapeutic Use];0 (Anti-Inflammatory Agents, Non-Steroidal);0 (Antineoplastic Agents);0 (Antineoplastic Agents, Hormonal);0 (Platelet Aggregation Inhibitors);0 (Quinazolines);47M74X9YT5 (Cladribine);78E4J5IB5J (Mitotane);97067-70-4 (Dihematoporphyrin Ether);FM5526K07A (Zinc Acetate);K9X45X0051 (anagrelide);WK2XYI10QM (Ibuprofen)","Joppi, R.;Gerardi, C.;Bertele, V.;Garattini, S.",2016,Jun 22,https://dx.doi.org/10.1136/bmj.i2978,0,0,
72,The predictive value of low plasma copper and high plasma zinc in detecting zinc-induced copper deficiency,"BACKGROUND: Zinc-induced copper deficiency is a condition whose diagnosis is often delayed allowing severe and usually irreversible neurology symptoms to develop. Plasma copper concentrations are usually low and plasma zinc concentrations high. The aim of this study was to measure the predictive value of this combination of results as a means of facilitating its early diagnosis. METHODS: Low plasma copper (<=6micro mol/L) and high plasma zinc results (>18micro mol/L) were retrieved from the laboratory database from 2000 to 2014. Medical records and laboratory notes of the corresponding 20 patients found were accessed to determine which were likely to have zinc-induced copper deficiency. RESULTS: Fifteen (75%) patients were diagnosed with zinc-induced copper deficiency which was symptomatic in 13. Of the five remaining patients, two were treated with zinc because of Wilson's disease which was the cause of hypocupraemia, two were treated parenterally with zinc, and insufficient information was available in the final patient. CONCLUSIONS: The combination of a low plasma copper and high plasma zinc is strongly predictive for the diagnosis of zinc-induced copper deficiency. There is the therefore an opportunity for the reporting biochemist to facilitate in its earlier diagnosis so enabling treatment to be implemented before the condition deteriorates. Copyright © The Author(s) 2016.","Adolescent;Adult;Aged;Aged, 80 and over;Copper/bl [Blood];*Copper/df [Deficiency];Early Diagnosis;Female;Humans;Male;Middle Aged;*Zinc/bl [Blood];789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Duncan, A.;Talwar, D.;Morrison, I.",2016,Sep,https://dx.doi.org/10.1177/0004563215620821,0,0,
73,Four-year follow-up of a Wilson disease pedigree complicated with epilepsy and hypopituitarism: Case report with a literature review,"RATIONALE: Wilson's disease (WD) is an autosomal recessive inherited disorder of copper metabolism with excellent prognosis if treated timely. However, WD is usually prone to neglect and misdiagnosis at an early stage. We reported a rare WD pedigree, and the clinical features, laboratory tests, and gene mutations were analyzed in detail. PATIENT CONCERNS: The patient was a 17-year-old and 136-cm-tall girl who presented with limb weakness, combined with multi-organ disorders including blind eye, epilepsy, and hypopituitarism. DIAGNOSES: Clinical tests showed a low serum ceruloplasmin level, high urinary copper excretion and Kayser-Fleischer (K-F) rings. She carried a compound heterozygous mutations in ATP7B gene (c.2828G>A and c.3884C>T). Her younger brother, as an asymptomatic patient, manifested with elevation of transaminases but without neurological and hepatic symptoms. They were diagnosed as WD finally. INTERVENTIONS: They were treated with sodium dimercaptosulphonate, supplemented with zinc gluconate, vitamin B6, vitamin C, as well as restriction of dietary copper. OUTCOMES: The urinary copper excretion and serum transaminase level decreased gradually. The abnormal signals in brainstem and basal ganglia were also remarkably decreased after 4-year of de-copper treatment. LESSONS: As to the patients with complicated clinical manifestations, the extrapyramidal symptom and basal ganglia signals should be concerned. The serum ceruloplasmin detection and ATP7B gene mutation screening are necessary.",Adolescent;Early Diagnosis;*Epilepsy/et [Etiology];Epilepsy/pp [Physiopathology];Epilepsy/th [Therapy];Female;Follow-Up Studies;*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];Humans;*Hypopituitarism/et [Etiology];Hypopituitarism/pp [Physiopathology];Hypopituitarism/th [Therapy];Lower Extremity;Muscle Weakness/di [Diagnosis];Muscle Weakness/et [Etiology];Pedigree;Risk Assessment,"Zhang, Q. J.;Xu, L. Q.;Wang, C.;Hu, W.;Wang, N.;Chen, W. J.",2016,Dec,https://dx.doi.org/10.1097/MD.0000000000005331,0,0,
74,"Molybdenum Metallopharmaceuticals Candidate Compounds - The ""Renaissance"" of Molybdenum Metallodrugs?","Metal-based drugs, also called ""metallopharmaceuticals"" or ""metallodrugs"", are examples of sophisticated compounds that have been used in inorganic medicinal chemistry as therapeutic agents for a long time. Few of them have shown substantially promising results and many of them have been used in different phases of clinical trials. The Mo-based metallodrugs were successfully applied in the past for treating conditions such as anemia or Wilson's disease. Moreover, Mo complexes are supposed to exert their effect by intercalation/ cleavage of DNA/RNA, arrest of the cell cycle, and alteration of cell membrane functions. However, in the current literature, there are no reliable and in-depth reviews about the hypothetical therapeutic applications of all of the known molybdenum complexes as metallopharmaceuticals/ metallodrugs. The main emphasis was on the in-depth review of the potential applications of Mo-based complexes in medicinal chemistry as metallopharmaceuticals in treating diseases such as cancer and tumors, Wilson's disease, diabetes mellitus, Huntington's disease, atherosclerosis, and anemia. It must be emphasized that today the development of innovative and new Mo-based metalo-pharmaceuticals is not rapid, and hence the aim of this paper was also to inspire colleagues working in the field of Mo compounds who are trying to find ""signpost"" for research. The authors hope that this article will increase interest and initiate the Renaissance of Mo-compounds among medicinal inorganic chemists. This paper is the first review article in the literature that refers to and emphasizes many different and complex aspects of possible applications and capabilities of Mo-based metallodrugs.",Animals;Atherosclerosis/dt [Drug Therapy];Atherosclerosis/pa [Pathology];Cell Cycle Checkpoints/de [Drug Effects];*Coordination Complexes/ch [Chemistry];Coordination Complexes/pd [Pharmacology];Coordination Complexes/tu [Therapeutic Use];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Huntington Disease/dt [Drug Therapy];Huntington Disease/pa [Pathology];*Molybdenum/ch [Chemistry];Molybdenum/tu [Therapeutic Use];Tungsten Compounds/ch [Chemistry];Tungsten Compounds/pd [Pharmacology];Tungsten Compounds/tu [Therapeutic Use];0 (Coordination Complexes);0 (Tungsten Compounds);0 (polyoxometalate I);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Jurowska, A.;Jurowski, K.;Szklarzewicz, J.;Buszewski, B.;Kalenik, T.;Piekoszewski, W.",2016,,,0,0,
75,Current Drug Managements of Wilson's Disease: From West to East,"Wilson's disease (WD), also called hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism characterized by the multiple mutations in the ATP-ase 7B gene of chromosome 13q. About half of the WD patients have neurological or psychiatric symptoms. As WD is a kind of medicable or nearly curable neurodegenerative disease in the field of medicine, early consideration/examination and without delay/ life-long treatment usually lead to better prognoses. The drugs, also named as anticopper agents, are commonly used in clinics including D-penicillamine, trientine, sodium dimercaptosuccinate, dimercaptosuccinic acid, zinc and tetrathiomolybdate. This provides detailed reviews about these medicines.","*Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Medicine, Chinese Traditional;Molybdenum/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Succimer/tu [Therapeutic Use];Treatment Outcome;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);DX1U2629QE (Succimer);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Li, W. J.;Chen, C.;You, Z. F.;Yang, R. M.;Wang, X. P.",2016,,,0,0,
76,Long-term metabolic correction of Wilson's disease in a murine model by gene therapy,"BACKGROUND & AIMS: Wilson's disease (WD) is an autosomal recessively inherited copper storage disorder due to mutations in the ATP7B gene that causes hepatic and neurologic symptoms. Current treatments are based on lifelong copper chelating drugs and zinc salts, which may cause side effects and do not restore normal copper metabolism. In this work we assessed the efficacy of gene therapy to treat this condition. METHODS: We transduced the liver of the Atp7b(-/-) WD mouse model with an adeno-associated vector serotype 8 (AAV8) encoding the human ATP7B cDNA placed under the control of the liver-specific alpha1-antitrypsin promoter (AAV8-AAT-ATP7B). After vector administration we carried out periodic evaluation of parameters associated with copper metabolism and disease progression. The animals were sacrificed 6months after treatment to analyze copper storage and hepatic histology. RESULTS: We observed a dose-dependent therapeutic effect of AAV8-AAT-ATP7B manifested by the reduction of serum transaminases and urinary copper excretion, normalization of serum holoceruloplasmin, and restoration of physiological biliary copper excretion in response to copper overload. The liver of treated animals showed normalization of copper content and absence of histological alterations. CONCLUSIONS: Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.","Adenosine Triphosphatases/ge [Genetics];Animals;Cation Transport Proteins/ge [Genetics];*Copper/me [Metabolism];Disease Models, Animal;Disease Progression;Gene Transfer Techniques;*Genetic Therapy/mt [Methods];*Genetic Vectors/ad [Administration & Dosage];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver/me [Metabolism];Liver/pa [Pathology];*Liver;Mice;Peptide Fragments/ge [Genetics];Treatment Outcome;alpha 1-Antitrypsin/ge [Genetics];0 (C105Y peptide);0 (Cation Transport Proteins);0 (Peptide Fragments);0 (alpha 1-Antitrypsin);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Atp7a protein, mouse);EC 3-6-3-4 (Wilson disease protein)","Murillo, O.;Luqui, D. M.;Gazquez, C.;Martinez-Espartosa, D.;Navarro-Blasco, I.;Monreal, J. I.;Guembe, L.;Moreno-Cermeno, A.;Corrales, F. J.;Prieto, J.;Hernandez-Alcoceba, R.;Gonzalez-Aseguinolaza, G.",2016,Feb,https://dx.doi.org/10.1016/j.jhep.2015.09.014,0,0,
77,Subclinical neurological involvement does not develop if Wilson's disease is treated early,"BACKGROUND & AIMS: Wilson's disease (WD) is a genetic disorder of copper metabolism causing dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset. METHODS: Thirty-eight WD patients (18 females, aged 24.47 +/- 7.50 years), who received an early diagnosis (in presymptomatic or mild/moderate liver disease stages without neurological involvement) and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were presymptomatic. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation. Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests. RESULTS: Patients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3 +/- 0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement. CONCLUSIONS: This study suggests that early diagnosis and treatment of WD may prevent the onset of neurologic damage, even at subclinical level. Copyright © 2016 Elsevier Ltd. All rights reserved.",Adenosine Triphosphatases/ge [Genetics];Adolescent;Adult;Analysis of Variance;Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Cation Transport Proteins/ge [Genetics];Disease Progression;Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/th [Therapy];Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Nervous System Diseases/di [Diagnosis];*Nervous System Diseases/et [Etiology];Nervous System Diseases/pc [Prevention & Control];Neurologic Examination;Neuropsychological Tests;Penicillamine/tu [Therapeutic Use];Psychiatric Status Rating Scales;Retrospective Studies;Young Adult;Zinc/tu [Therapeutic Use];0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Dubbioso, R.;Ranucci, G.;Esposito, M.;Di Dato, F.;Topa, A.;Quarantelli, M.;Matarazzo, M.;Santoro, L.;Manganelli, F.;Iorio, R.",2016,Mar,https://dx.doi.org/10.1016/j.parkreldis.2016.01.024,0,1,
78,INTERACTIVE MEDICAL CASE. Tracing the Cause of Abdominal Pain,,*Abdominal Pain/et [Etiology];Biopsy;Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Copper/an [Analysis];Copper/me [Metabolism];Copper/ur [Urine];*Fanconi Syndrome/di [Diagnosis];Fanconi Syndrome/et [Etiology];Female;Gallbladder/dg [Diagnostic Imaging];Gallbladder/pa [Pathology];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/ch [Chemistry];*Liver/pa [Pathology];Spleen/dg [Diagnostic Imaging];Transaminases/bl [Blood];Trientine/tu [Therapeutic Use];Ultrasonography;Young Adult;0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1 (Transaminases);SJ76Y07H5F (Trientine),"Nayor, J.;Vaidya, A.;Srivastava, A.;Seifter, J. L.;Rutherford, A. E.",2016,Aug 11,https://dx.doi.org/10.1056/NEJMimc1512611,0,0,
79,[Wilson-Konovalov's Disease in Two Sisters: Differences in the Clinical Picture and Successful Therapy],"Wilson-Konovalov's disease is a rare genetic pathology of copper metabolism that in the first place affects liver and CNS. Due to autosomal-recessive inheritance of this condition, it most frequently occurs in sibs. We report a case of Wilson-Konovalov's disease in two sisters differing in its clinical course: severe abdominal variant in the younger sister and largely neurologic form in the elder one. This observation demonstrates clinical variability of Wilson-Konovalov's disease, the possibility of its late clinical manifestation (at the age 45 years), the necessity of examination of all sibs of a proband regardless of age, and the possibility of radical improvement of prognosis even when the disease is diagnosed at the stage of decompensated liver cirrhosis.","Adenosine Triphosphatases/an [Analysis];Adult;Brain/pa [Pathology];Brain/pp [Physiopathology];*Brain;Cation Transport Proteins/an [Analysis];Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];*Copper/me [Metabolism];Diagnostic Techniques, Ophthalmological;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration;Humans;Liver/pa [Pathology];Liver/pp [Physiopathology];*Liver;Middle Aged;Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];*Penicillamine;Siblings;Treatment Outcome;0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Ignatova, T. M.;Solov'eva, O. V.;Arion, E. A.;Balashova, M. S.;Rozina, T. P.",2016,,,0,0,
80,Novel Zeb2 gene variation in the Mowat Wilson syndrome (MWS),"BACKGROUND: Mowat Wilson syndrome (MWS) is an uncommon association of Hirschsprung's disease (HSCR). Phenotypic features may develop with time, causing initial difficulties in diagnosis. MWS results from haploinsufficiency of the Zinc finger E-box-binding homeobox 2 (ZEB2) gene, and molecular diagnosis of ZEB2 mutation is required to confirm the diagnosis. We report the first confirmed cases of MWS in three children with the typical facial features, mental retardation, absent corpus callosum, epilepsy, and HSCR and novel Zeb2 variations on DNA analysis. METHODOLOGY: Clinical features were monitored. DNA extracted from peripheral blood was subjected to bidirectional sequencing analysis following PCR DNA amplification. ZEB2 gene results were compared to the ZEB2 reference sequence (ENS00000169554) for variation. Bioinformatic investigation of novel gene variants was via the ""Blastx"" program function available via the National Center for Biotechnology Information (http://www.bioinfo.org/NPInter/blast/blast_link.cgi). RESULTS: Clinical follow-up showed that the phenotypic features were not all present at birth but developed with time in 2 surviving patients. Several Zeb2 variations were detected in the promoter region of the ZEB2 gene of which 2 were novel (-56A/T 1174 11A/12A). In addition, a novel heterozygous single nucleotide insertion in exon 2 of ZEB2 in one patient results in a frameshift causing deletion of the first 8 amino acids of the ZEB2 protein and an alteration of amino acids 9 (G9A), 11 (R11G), and 12 (C12A). In the third patient, a novel single nucleotide deletion exon 8 (1784delC Het) results in a frameshift at amino acid 595 of translated protein. This shortens protein from 1214 to 594 amino acids and affects the functionality of the critical ZEB2 protein. CONCLUSIONS: MWS is an important link to recognise clinically. It underlines the functionality of the Zeb2 gene in certain syndromic Hirschsprung's disease. These variations probably contribute to the clinical features of the Mowat Wilson phenotype in Hirschsprung's disease but should be confirmed in further research. Copyright © 2016 Elsevier Inc. All rights reserved.","Child;Child, Preschool;Facies;Female;Genetic Markers;Hirschsprung Disease/di [Diagnosis];*Hirschsprung Disease/ge [Genetics];*Homeodomain Proteins/ge [Genetics];Humans;Infant;Infant, Newborn;Intellectual Disability/di [Diagnosis];*Intellectual Disability/ge [Genetics];Male;Microcephaly/di [Diagnosis];*Microcephaly/ge [Genetics];*Mutation;Phenotype;*Repressor Proteins/ge [Genetics];0 (Genetic Markers);0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human);Mowat-Wilson syndrome","Moore, S. W.;Fieggen, K.;Honey, E.;Zaahl, M.",2016,Feb,https://dx.doi.org/10.1016/j.jpedsurg.2015.10.070,0,0,
81,D-penicillamine-induced ANA (+) ANCA (+) vasculitis in pediatric patients with Wilson's disease,"Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with systemic vasculitis. The pathophysiology of ANCA-associated vasculitis (AAV) has not been clearly proven, and drug-induced ANCA-associated vasculitis has been reported. Wilson's disease is an inborn error of copper metabolism caused by a mutation in the copper transporting gene ATP7B, and traditional treatment is based on copper chelation with agents such as D-penicillamine. There have been rare reports that prolonged D-penicillamine therapy might cause adverse renal events such as membranous nephropathy and minimal change disease, but it is questionable if D-penicillamine induces ANCA-associated vasculitis. We describe 2 patients with Wilson's disease treated with D-penicillamine who presented with ANCA (+) vasculitis and renal involvement. The 2 patients also showed positive results for antinuclear antibody (ANA). Their kidney biopsy findings were compatible with crescentic/necrotizing glomerulonephritis, pauci-immune type. After diagnosis of AAV, D-penicillamine was stopped. Patients were then treated with plasmapheresis and immunosuppressants, including methylprednisolone pulse therapy and intravenous cyclophosphamide. One patient progressed to end-stage renal disease and the other showed persistent proteinuria. These cases suggest that D-penicillamine may induce ANA (+) ANCA (+) vasculitis with severe renal involvement in pediatric patients, and plasmapheresis combined with immunosuppressant should be considered.","Adolescent;*Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/ci [Chemically Induced];Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/dt [Drug Therapy];Antibodies, Antineutrophil Cytoplasmic/bl [Blood];Antibodies, Antinuclear/bl [Blood];*Chelating Agents/ae [Adverse Effects];Female;*Glomerulonephritis/ci [Chemically Induced];Glomerulonephritis/dt [Drug Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];0 (Antibodies, Antineutrophil Cytoplasmic);0 (Antibodies, Antinuclear);0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Lee, Y.;Lee, S. T.;Cho, H.",2016,May,https://dx.doi.org/10.5414/CN108763,0,0,
82,Combined zinc sulphate and NSAID-induced gastric ulcer perforation in Wilson disease: A case report,,"Anti-Inflammatory Agents, Non-Steroidal/ad [Administration & Dosage];*Anti-Inflammatory Agents, Non-Steroidal/ae [Adverse Effects];Drug Therapy, Combination/ae [Adverse Effects];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Stomach Ulcer/ci [Chemically Induced];Young Adult;Zinc Sulfate/ad [Administration & Dosage];*Zinc Sulfate/ae [Adverse Effects];0 (Anti-Inflammatory Agents, Non-Steroidal);7733-02-0 (Zinc Sulfate)","Gilbert, A.;Doussot, A.;Lagoutte, N.;Facy, O.;Cheynel, N.;Rat, P.",2016,Feb,https://dx.doi.org/10.1016/j.clinre.2015.07.003,0,0,
83,Concomitant immune-related events in Wilson disease: implications for monitoring chelator therapy,"BACKGROUND AND AIMS: Current guidelines favor the use of chelating agents (d-penicillamine, trientine) in first line therapy of symptomatic Wilson disease patients. Development of chelator induced immunological adverse events are a concern especially under d-penicillamine therapy. This study assessed the prevalence of co-existing or therapy-related immune-mediated diseases in Wilson disease patients, and evaluated the role of antinuclear antibodies in therapy monitoring. METHODS: We retrospectively analyzed 235 Wilson disease patients. Medical regimens were classified and analyzed in relation to adverse events and antinuclear antibody courses. RESULTS: Coexisting immune-mediated diseases were evident in 19/235 (8.1%) patients, of which 13/235 (5.5%) had pre-existing autoimmune diseases. Six patients (2.6%) developed an autoimmune disease under therapy, all of them under long-term d-penicillamine treatment. Data relating to antinuclear antibody courses during treatment and adverse events were available for patients treated with d-penicillamine (n=91), trientine (n=58), and zinc salts (n=58). No significant increase in antinuclear antibody titers in patients treated with d-penicillamine (16/91; 17.6%), trientine (12/58; 20.7%), and zinc (7/58; 12.1%) were found. CONCLUSION: Under long-term d-penicillamine therapy a minority of patients developed immune-mediated disease. Elevations in antinuclear antibodies were found frequently, but no correlations were evident between increases in antinuclear antibodies and the development of immune-mediated diseases or medical regimes. Thus, the value of antinuclear antibodies for monitoring adverse events under chelator therapy seems to be limited.","Adolescent;Adult;Antibodies, Antinuclear/im [Immunology];Autoimmune Diseases/ci [Chemically Induced];Autoimmune Diseases/im [Immunology];*Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];Child;Cross-Sectional Studies;Drug Monitoring/mt [Methods];*Drug-Related Side Effects and Adverse Reactions/im [Immunology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/im [Immunology];Humans;Male;Penicillamine/ae [Adverse Effects];Penicillamine/im [Immunology];Penicillamine/tu [Therapeutic Use];Retrospective Studies;Trientine/ae [Adverse Effects];Trientine/im [Immunology];Trientine/tu [Therapeutic Use];Young Adult;Zinc/ae [Adverse Effects];Zinc/im [Immunology];Zinc/tu [Therapeutic Use];0 (Antibodies, Antinuclear);0 (Chelating Agents);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Seessle, J.;Gotthardt, D. N.;Schafer, M.;Gohdes, A.;Pfeiffenberger, J.;Ferenci, P.;Stremmel, W.;Weiss, K. H.",2016,Jan,https://dx.doi.org/10.1007/s10545-015-9866-0,1,1,
84,Wilson's disease with cognitive impairment and without extrapyramidal signs: improvement of neuropsychological performance and reduction of MRI abnormalities with trientine treatment,"Extrapyramidal signs are neurological dysfunction commonly associated with Wilson's disease (WD). In addition, cognitive dysfunction has been reported in the early stages of WD. In this report, we describe a 49-year-old woman presenting with memory impairments and without Parkinsonian or extrapyramidal signs. She was diagnosed with WD based on the presence of Kayser-Fleischer rings around the irises of her eyes and two ATP7B gene mutations, R778L at exon 8 and A874V at exdyon 11. Serial magnetic resonance imaging analysis and neuropsychological tests showed improvements following treatment with trientine.",*Brain/de [Drug Effects];Brain/pa [Pathology];Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];Cognition Disorders/co [Complications];*Cognition Disorders/dt [Drug Therapy];Cognition Disorders/pa [Pathology];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Middle Aged;Neuropsychological Tests;Treatment Outcome;Trientine/pd [Pharmacology];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);SJ76Y07H5F (Trientine),"Chung, E. J.;Kim, E. G.;Kim, S. J.;Ji, K. H.;Seo, J. H.",2016,,https://dx.doi.org/10.1080/13554794.2015.1032977,0,0,
85,Measurement of urinary copper excretion after 48-h d-penicillamine cessation as a compliance assessment in Wilson's disease,"Treatment of Wilson's disease (WD) with anti-copper agents is effective in most compliant patients. During long-term treatment with chelating agents, a two-day interruption of the treatment should result in normal urinary copper concentrations (<50 mug/dl). The aim of this study was to establish the usefulness of this method as a compliance assessment in these patients. We examined consecutive patients treated with d-penicillamine (DPA) undergoing routine follow-up studies at our center. We performed 24-h urinary copper excretion analysis 48 h after interruption of chelating therapy. Thirty-two patients were enrolled. After DPA cessation, normalization of copper excretion was observed in 91% of reportedly compliant patients. The specificity and sensitivity values of this test were 87% and 77%, respectively. Measurement of 24-h urinary copper excretion after a 48-h interruption of DPA therapy in patients with WD is a reliable method for confirming patients' compliance.",Adult;Aged;Chelating Agents/ad [Administration & Dosage];*Chelating Agents/tu [Therapeutic Use];*Copper/ur [Urine];Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Time Factors;Treatment Outcome;Young Adult;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Dziezyc, K.;Litwin, T.;Chabik, G.;Czlonkowska, A.",2015,Oct-Dec,,0,0,
86,Trientine induced colitis during therapy for Wilson disease: a case report and review of the literature,"BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder of human copper metabolism characterized by copper accumulation in the liver due to impaired excretion of copper into the bile. Brain accumulation of copper may cause neuropsychiatric symptoms. Trientine (triethylenetetramine dihydrochloride) is a copper-chelating agent used to treat patients with WD. Trientine has been considered an option for initial treatment and maintentance therapy of WD due to its safety profile. CASE PRESENTATION: A 40 year old female with a recent diagnosis of WD was started on treatment with trientine for her WD. Within one month she developed profound bloody diarrhea unresponsive to medical treatment. Trientine was discontinued and a colonoscopy with biopsy showed moderately active ileitis and moderate to severe pancolitis, consistent with a drug induced mucosal injury. The colitis improved immediately upon withdrawal of trientine, and recurred when medication was rechallenged because of worsened WD symptoms. After second compulsory discontinuation of trientine, she remained on zinc therapy for her WD and her colitis resolved by time. CONCLUSION: Drug induced colitis is a very rare side effect of trientine. Although trientine therapy is well tolerated and less side effects are reported with this medication than penicillamine, colitis can occur during trientine treatment. Zinc therapy may be an effective alternative for treatment of WD in patients experiencing side effects from chelation therapy.",Adult;Chelating Agents/ae [Adverse Effects];*Colitis/ci [Chemically Induced];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Trientine/ae [Adverse Effects];Withholding Treatment;0 (Chelating Agents);SJ76Y07H5F (Trientine),"Boga, S.;Jain, D.;Schilsky, M. L.",2015,Nov 20,https://dx.doi.org/10.1186/s40360-015-0031-z,0,0,
87,The spectrum of psychiatric symptoms in Wilson's disease: treatment and prognostic considerations,,Adult;Antidepressive Agents/tu [Therapeutic Use];Antipsychotic Agents/tu [Therapeutic Use];Capgras Syndrome/dt [Drug Therapy];Capgras Syndrome/et [Etiology];*Capgras Syndrome/px [Psychology];Chelating Agents/tu [Therapeutic Use];Depressive Disorder/dt [Drug Therapy];Depressive Disorder/et [Etiology];*Depressive Disorder/px [Psychology];Disease Progression;Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/px [Psychology];Humans;Prognosis;Psychotic Disorders/dt [Drug Therapy];Psychotic Disorders/et [Etiology];*Psychotic Disorders/px [Psychology];Trace Elements/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Antidepressive Agents);0 (Antipsychotic Agents);0 (Chelating Agents);0 (Trace Elements);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Zimbrean, P. C.;Schilsky, M. L.",2015,Nov 01,https://dx.doi.org/10.1176/appi.ajp.2015.15030371,0,0,
88,"Formation constants of copper(I) complexes with cysteine, penicillamine and glutathione: implications for copper speciation in the human eye","Protonation constants for the biologically-important thioamino acids cysteine (CSH), penicillamine (PSH) and glutathione (GSH), and the formation constants of their complexes with Cu(I), have been measured at 25 degreeC and an ionic strength of 1.00 mol dm(-3) (Na)Cl using glass electrode potentiometry. The first successful characterisation of binary Cu(I)-CSH and Cu(I)-GSH species over the whole pH range was achieved in this study by the addition of a second thioamino acid, which prevented the precipitation that normally occurs. Appropriate combinations of binary and ternary (mixed ligand) titration data were used to optimise the speciation models and formation constants for the binary species. The results obtained differ significantly from literature data with respect to the detection and quantification of protonated and polynuclear complexes. The present results are thought to be more reliable because of the exceptionally wide pH and concentration ranges employed, the excellent reproducibility of the data, the close agreement between the calculated and observed formation functions, and the low standard deviations and absence of numerical correlation in the constants. The present formation constants were incorporated into a large Cu speciation model which was used to predict, for the first time, metal-ligand equilibria in the biofluids of the human eye. This simulation provided an explanation for the precipitation of metallic copper in lens and cornea, which is known to occur as a consequence of Wilson's disease.","Computer Simulation;*Coordination Complexes/ch [Chemistry];*Copper/ch [Chemistry];*Cysteine/ch [Chemistry];Eye;*Glutathione/ch [Chemistry];Humans;Hydrogen-Ion Concentration;*Models, Biological;*Penicillamine/ch [Chemistry];Potentiometry;0 (Coordination Complexes);789U1901C5 (Copper);GAN16C9B8O (Glutathione);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine)","Konigsberger, L. C.;Konigsberger, E.;Hefter, G.;May, P. M.",2015,Dec 21,https://dx.doi.org/10.1039/c5dt02129d,0,0,
89,Wilson disease with hepatic presentation in an eight-month-old boy,"Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7B gene detected two heterozygous disease causing mutations (c.2621C>T/p.A874V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.",Adenosine Triphosphatases/ge [Genetics];Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Biomarkers/bl [Blood];Cation Transport Proteins/ge [Genetics];Ceruloplasmin/an [Analysis];DNA Mutational Analysis;Genetic Predisposition to Disease;Gluconates/tu [Therapeutic Use];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Heterozygote;Humans;Infant;Liver Function Tests;Male;Mutation;Phenotype;Predictive Value of Tests;Treatment Outcome;0 (Biomarkers);0 (Cation Transport Proteins);0 (Gluconates);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);R4R8J0Q44B (gluconic acid),"Abuduxikuer, K.;Li, L. T.;Qiu, Y. L.;Wang, N. L.;Wang, J. S.",2015,Aug 07,https://dx.doi.org/10.3748/wjg.v21.i29.8981,0,0,
90,Elevated copper impairs hepatic nuclear receptor function in Wilson's disease,"Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b-/- mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4alpha, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b-/- mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.","Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Adult;Animals;Cation Transport Proteins/ge [Genetics];Cation Transport Proteins/me [Metabolism];Cholestasis, Intrahepatic/ge [Genetics];Cholestasis, Intrahepatic/me [Metabolism];Cholestasis, Intrahepatic/pa [Pathology];*Copper/me [Metabolism];Female;Hepatolenticular Degeneration;Humans;*Liver/me [Metabolism];Liver/pa [Pathology];Male;Mice;Mice, Knockout;P-Glycoproteins/df [Deficiency];P-Glycoproteins/ge [Genetics];P-Glycoproteins/me [Metabolism];Receptors, Cytoplasmic and Nuclear/ge [Genetics];*Receptors, Cytoplasmic and Nuclear/me [Metabolism];Response Elements;0 (Cation Transport Proteins);0 (P-Glycoproteins);0 (Receptors, Cytoplasmic and Nuclear);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Atp7a protein, mouse);EC 3-6-3-4 (Wilson disease protein);Cholestasis, progressive familial intrahepatic 2;Cholestasis, progressive familial intrahepatic 3","Wooton-Kee, C. R.;Jain, A. K.;Wagner, M.;Grusak, M. A.;Finegold, M. J.;Lutsenko, S.;Moore, D. D.",2015,Sep,https://dx.doi.org/10.1172/JCI78991,0,0,
91,Zinc Therapy for Wilson Disease in Children in French Pediatric Centers,"BACKGROUND AND AIMS: Zinc therapy is considered a good option in Wilson disease (WD), as a first-line treatment in presymptomatic children and a maintenance therapy after the initial chelator therapy. The aim of the study was to determine the practical use of zinc treatment in French pediatric centers. METHODS: A national survey was conducted in the 6 French centers using zinc acetate to treat WD. Clinical and biological parameters, dosage, and outcome were recorded. RESULTS: A total of 26 children were reported to be treated with zinc acetate, alone or in association with chelators. Of the 9 children (35%) who received zinc alone as a first-line therapy, 2 were switched to D-penicillamine because of inefficacy and 7 remained on zinc alone, but serum transaminase levels normalized in only 4 of them. Five children (19%) were initially treated with zinc in association with D-penicillamine (n = 4) or Trientine (n = 1) with good efficacy. Among the 12 children (46%) who received zinc as a maintenance therapy after D-penicillamine, no relapse of hepatic cytolysis occurred during a median follow-up of 5.2 years, but 2 of them were switched to Trientine because of zinc-related adverse effects. Epigastric pain was observed in 4 children, and a gastric perforation occurred in 1 child. CONCLUSIONS: The present study demonstrates poor efficacy of zinc as first-line therapy to control liver disease in half presymptomatic children and a high incidence of related gastrointestinal adverse effects in children with WD.","Abdominal Pain/et [Etiology];Adolescent;*Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Copper/me [Metabolism];Female;France;Health Care Surveys;Health Facilities;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Infant;*Liver/de [Drug Effects];Liver/me [Metabolism];Liver/pa [Pathology];Male;Pediatrics;*Penicillamine/tu [Therapeutic Use];Retrospective Studies;Stomach/de [Drug Effects];Trace Elements/ae [Adverse Effects];Trace Elements/me [Metabolism];*Trace Elements/tu [Therapeutic Use];Transaminases/bl [Blood];Treatment Outcome;Trientine;Zinc/ae [Adverse Effects];*Zinc/tu [Therapeutic Use];Zinc Acetate/ae [Adverse Effects];Zinc Acetate/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);789U1901C5 (Copper);EC 2-6-1 (Transaminases);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Santiago, R.;Gottrand, F.;Debray, D.;Bridoux, L.;Lachaux, A.;Morali, A.;Lapeyre, D.;Lamireau, T.",2015,Dec,https://dx.doi.org/10.1097/MPG.0000000000000926,0,1,
92,Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy,"Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there is no study evaluating the role of oxidative stress. We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naive NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was one or more grade deterioration in severity scale, >10 % deterioration in BFM score or appearance of new neurologic signs. The median age of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25 patients improved, 12 worsened, and 14 had stationary course. The worsened group at 3 months had lower GSH (1.99 +/- 0.17 vs. 2.30 +/- 0.30 mg/dl; P = 0.004) and TAC (1.59 +/- 0.12 vs. 1.82 +/- 0.17 mmol Trolox equivalent/L; P = 0.001) and higher MDA (5.24 +/- 0.22 vs. 4.34 +/- 0.46 nmol/ml; P < 0.001) levels compared to the improved group. These changes were associated with increased serum free Cu (41.81 +/- 3.31 vs. 35.62 +/- 6.40 micro g/dl; P = 0.02) and 24-h urinary Cu (206.42 +/- 41.61 vs. 121.99 +/- 23.72 micro g/24 h; P < 0.001) in the worsened compared to the improved group. All the patients having worsening were on penicillamine. Worsening following chelating treatment in NWD may be due to oxidative stress which is induced by increased serum free Cu. These results may have future therapeutic implication and needs further study.","Adolescent;Adult;Antioxidants/an [Analysis];*Chelating Agents/ae [Adverse Effects];*Chelation Therapy/ae [Adverse Effects];Child;Child, Preschool;Copper/bl [Blood];Copper/ur [Urine];*Copper;Disease Progression;Female;Glutathione/bl [Blood];Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;International Normalized Ratio;Kidney/pp [Physiopathology];Lipid Peroxidation;Liver/dg [Diagnostic Imaging];Liver/pp [Physiopathology];Magnetic Resonance Imaging;Male;Malondialdehyde/bl [Blood];*Oxidative Stress;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Severity of Illness Index;Spleen/dg [Diagnostic Imaging];Treatment Outcome;Ultrasonography;Young Adult;*Zinc/ae [Adverse Effects];Zinc/tu [Therapeutic Use];0 (Antioxidants);0 (Chelating Agents);4Y8F71G49Q (Malondialdehyde);789U1901C5 (Copper);GAN16C9B8O (Glutathione);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Kalita, J.;Kumar, V.;Ranjan, A.;Misra, U. K.",2015,Dec,https://dx.doi.org/10.1007/s12017-015-8364-8,0,0,
93,Zeb2: A multifunctional regulator of nervous system development,"Zinc finger E-box binding homeobox (Zeb) 2 is a transcription factor, identified due its ability to bind Smad proteins, and consists of multiple functional domains which interact with a variety of transcriptional co-effectors. The complex nature of the Zeb2, both at its genetic and protein levels, underlie its multifunctional properties, with Zeb2 capable of acting individually or as part of a transcriptional complex to repress, and occasionally activate, target gene expression. This review introduces Zeb2 as an essential regulator of nervous system development. Zeb2 is expressed in the nervous system throughout its development, indicating its importance in neurogenic and gliogenic processes. Indeed, mutation of Zeb2 has dramatic neurological consequences both in animal models, and in humans with Mowat-Wilson syndrome, which results from heterozygous ZEB2 mutations. The mechanisms by which Zeb2 regulates the induction of the neuroectoderm (CNS primordium) and the neural crest (PNS primordium) are reviewed herein. We then describe how Zeb2 acts to direct the formation, delamination, migration and specification of neural crest cells. Zeb2 regulation of the development of a number of cerebral regions, including the neocortex and hippocampus, are then described. The diverse molecular mechanisms mediating Zeb2-directed development of various neuronal and glial populations are reviewed. The role of Zeb2 in spinal cord and enteric nervous system development is outlined, while its essential function in CNS myelination is also described. Finally, this review discusses how the neurodevelopmental defects of Zeb2 mutant mice delineate the developmental dysfunctions underpinning the multiple neurological defects observed in Mowat-Wilson syndrome patients. Copyright © 2015 Elsevier Ltd. All rights reserved.","Animals;Animals, Genetically Modified;*Homeodomain Proteins/ge [Genetics];*Homeodomain Proteins/me [Metabolism];Humans;Nervous System/em [Embryology];Nervous System/gd [Growth & Development];Nervous System/me [Metabolism];*Nervous System;*Repressor Proteins/ge [Genetics];*Repressor Proteins/me [Metabolism];0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Hegarty, S. V.;Sullivan, A. M.;O'Keeffe, G. W.",2015,Sep,https://dx.doi.org/10.1016/j.pneurobio.2015.07.001,0,0,
94,Coagulation Parameters in Wilson Disease,"BACKGROUND & AIMS: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. Alterations of copper metabolism have been associated with changes in coagulation factors. The aim of the present study was the analysis of coagulation factors in WD patients. METHODS: 100 patients attending a tertiary WD outpatient clinic were analyzed in a prospective cross sectional cohort study. Out of peripheral venous blood samples coagulation factors were assessed including: full blood count, INR, partial thromboplastin time (PTT), clotting factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand factor/-antigen, fibrinogen, antithrombin III, protein S, protein C, activated protein C (APC) resistance. Subgroup analyses of the blood tests were performed for sex, initial clinical presentation, WD treatment and liver function. RESULTS: Subgroup analysis by liver function showed decreased levels of factors II, V, VII and X. Subgroup analysis by gender or clinical course of the disease did not reveal significant coagulation changes. In patients treated with trientine significantly decreased levels of factors II, VII and antithrombin III and increased von Willebrand factor/-antigen levels were detected. Factor VIII levels were significantly reduced in patients receiving zinc. CONCLUSION: Although significant differences of some coagulation parameters in subgroup analysis were found, no clinically relevant alterations of the coagulation system in WD patients could be detected.",Adult;Biomarkers/bl [Blood];Blood Coagulation/de [Drug Effects];*Blood Coagulation;*Blood Coagulation Factors/an [Analysis];Chelating Agents/tu [Therapeutic Use];Cross-Sectional Studies;Female;*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;International Normalized Ratio;Liver Function Tests;Male;Partial Thromboplastin Time;Penicillamine/tu [Therapeutic Use];Predictive Value of Tests;Prospective Studies;Tertiary Care Centers;Trientine/tu [Therapeutic Use];Zinc Compounds/tu [Therapeutic Use];0 (Biomarkers);0 (Blood Coagulation Factors);0 (Chelating Agents);0 (Zinc Compounds);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Schaefer, M.;Weber, L.;Gotthardt, D.;Seessle, J.;Stremmel, W.;Pfeiffenberger, J.;Weiss, K. H.",2015,Jun,https://dx.doi.org/10.15403/jgld.2014.1121.242.wls,0,0,
95,Early neurological worsening in patients with Wilson's disease,"BACKGROUND: Early neurological worsening during treatment initiation for Wilson's disease (WD) is an unresolved problem. Our aim was to establish the frequency and outcome of early neurological worsening in patients with WD. METHODS: We analyzed 143 symptomatic patients diagnosed with WD between 2005 and 2009. Early neurological deterioration was based on worsening on the Unified Wilson's Disease Score Scale, scored at baseline through 6 months or occurrence of new neurological symptoms. Reversibility of worsening was followed up to 24 months. RESULTS: Early neurological worsening was observed in 11.1% (16/143) and involved only patients with neurological signs at diagnosis. Mean time to worsening from treatment initiation was 2.3 +/- 1.9 months. Neurological deterioration was completely reversible in 53% (8/15) and partially in 13% (2/15) of patients over 9.2 +/- 5.2 months. Patients who experienced early deterioration had significantly more severe baseline neurological deficit, higher prevalence of thalamic (66% vs 29%) and brain stem (73% vs 33%) lesions seen on baseline magnetic resonance imaging, and more often used concomitant dopamine receptor antagonists (46% vs 5%). Disease duration, treatment type (d-penicillamine or zinc sulfate), type of neurological manifestations, initial copper metabolism results, and liver function parameters did not differ between evaluated groups. CONCLUSIONS: Neurological worsening at the beginning of anti-copper therapy may occur in over 10% of WD patients. Special attention should be paid to those with severe initial neurological manifestations, advanced brain injury and using dopamine receptor antagonists. Type of anti-copper therapy did not show clear association with early neurological worsening. Copyright © 2015 Elsevier B.V. All rights reserved.",Adolescent;Adult;Brain/pa [Pathology];Copper/me [Metabolism];Dopamine Agents/tu [Therapeutic Use];Female;Follow-Up Studies;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Male;Nervous System Diseases/di [Diagnosis];Nervous System Diseases/dt [Drug Therapy];*Nervous System Diseases/et [Etiology];Neurologic Examination;Retrospective Studies;Treatment Outcome;Young Adult;0 (Dopamine Agents);789U1901C5 (Copper),"Litwin, T.;Dziezyc, K.;Karlinski, M.;Chabik, G.;Czepiel, W.;Czlonkowska, A.",2015,Aug 15,https://dx.doi.org/10.1016/j.jns.2015.06.010,1,1,
96,MRI and oxidative stress markers in neurological worsening of Wilson disease following penicillamine,"BACKGROUND AND AIM: There is no report of MRI correlation with neurological worsening following chelating treatment in Wilson disease with neurological manifestation (WDN). We report radiological changes in four patients with WDN who worsen after penicillamine. METHODS: WDN was diagnosed on the basis of clinical, KF ring, serum ceruloplasmin and 24h urinary copper. Hematological, biochemical and cranial MRI were repeated at the time of clinical deterioration following chelating treatment. RESULTS: Four WDN patients had neurological deterioration within 4-8 weeks of penicillamine therapy. This was associated with new lesions in white matter, thalamus, pons and mid brain and these lesions showed diffusion restriction. The neurologic deterioration was associated with increased free serum copper and malanodialdehyde and reduced glutathione. Clinical conditions stabilized after few weeks of penicillamine discontinuation. CONCLUSION: Neurological worsening was associated with new lesions on MRI which revealed diffusion restriction. Increased free copper induced oxidative stress may be responsible for these changes. Copyright © 2015 Elsevier Inc. All rights reserved.",Adult;*Antidotes/ae [Adverse Effects];Child;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Male;*Nervous System Diseases/ci [Chemically Induced];Nervous System Diseases/et [Etiology];*Nervous System Diseases/pa [Pathology];*Oxidative Stress/de [Drug Effects];*Penicillamine/ae [Adverse Effects];Time Factors;Young Adult;0 (Antidotes);GNN1DV99GX (Penicillamine),"Ranjan, A.;Kalita, J.;Kumar, V.;Misra, U. K.",2015,Jul,https://dx.doi.org/10.1016/j.neuro.2015.05.004,0,0,
97,Sunflower cataract: do not forget Wilson's disease,"A 41-year-old man with liver cirrhosis of unknown aetiology for 6 years was admitted to our department to confirm the diagnosis of Wilson's disease. He consulted an ophthalmologist who suspected the presence of a sunflower cataract and Kayser-Fleischer ring. At admission, his liver function tests were modestly impaired (Child-Pugh C, 10 pts). Neurological examination was normal, but cognitive functions were mildly impaired. Based on the copper metabolism abnormalities and clinical manifestation, we diagnosed Wilson's disease (Ferenci score, 6 pts) and started treatment with d-penicillamine. Presenting the case we would like to emphasise the significance of the ophthalmological examination in Wilson's disease diagnosis. Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.","Adult;*Cataract/di [Diagnosis];*Cataract/et [Etiology];Diagnostic Techniques, Ophthalmological;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Humans;Liver Cirrhosis/et [Etiology];Male","Litwin, T.;Langwinska-Wosko, E.;Dziezyc, K.;Czlonkowska, A.",2015,Oct,https://dx.doi.org/10.1136/practneurol-2014-001056,0,0,
98,Hypersomnolence in Wilson Disease,"ABSTRACT: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism resulting in copper accumulation in a number of organs including the liver, brain, and cornea, predominantly leading to hepatic, neurologic, and psychiatric manifestations. An association between WD and sleep problems is not commonly recognized, and sleep complaints are often overlooked. Daytime hypersomnolence is even more rarely reported in this population. We report a case of WD and hypersomnolence objectively confirmed by a multiple sleep latency test (MSLT). Consequently, we suggest that increased awareness, assessment, and treatment of sleep disorders, including daytime sleepiness, may help improve patients' quality of life. Copyright © 2015 American Academy of Sleep Medicine.",Adult;*Disorders of Excessive Somnolence/et [Etiology];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Polysomnography;Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc),"Amann, V. C.;Maru, N. K.;Jain, V.",2015,Nov 15,https://dx.doi.org/10.5664/jcsm.5204,0,0,
99,Clinical zinc deficiency as early presentation of Wilson disease,"Wilson disease is a rare autosomal recessive disorder of the copper metabolism caused by homozygous or compound heterozygous mutations in the ATP-ase Cu(2+) transporting polypeptide (ATP7B) gene. The copper accumulation in different organs leads to the suspicion of Wilson disease. We describe a child with clinical zinc deficiency as presenting symptom of Wilson disease, which was confirmed by 2 mutations within the ATP7B gene and an increased copper excretion.","*Adenosine Triphosphatases/ge [Genetics];Biological Transport;*Cation Transport Proteins/ge [Genetics];Child, Preschool;*Copper/me [Metabolism];Deficiency Diseases/et [Etiology];*Deficiency Diseases/ge [Genetics];Deficiency Diseases/me [Metabolism];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/pa [Pathology];Homozygote;Humans;Liver/me [Metabolism];Male;*Mutation;*Zinc/df [Deficiency];Zinc/me [Metabolism];0 (Cation Transport Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc)","Van Biervliet, S.;Kury, S.;De Bruyne, R.;Vanakker, O. M.;Schmitt, S.;Vande Velde, S.;Blouin, E.;Bezieau, S.",2015,Apr,https://dx.doi.org/10.1097/MPG.0000000000000628,0,0,
100,"Fair pricing of ""old"" orphan drugs: considerations for Canada's orphan drug policy",,Canada;Chelating Agents/ec [Economics];Chelating Agents/tu [Therapeutic Use];Costs and Cost Analysis/ec [Economics];*Costs and Cost Analysis/lj [Legislation & Jurisprudence];*Drug Costs/lj [Legislation & Jurisprudence];Health Policy;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ec [Economics];Humans;Orphan Drug Production/ec [Economics];*Orphan Drug Production/lj [Legislation & Jurisprudence];Rare Diseases/dt [Drug Therapy];Rare Diseases/ec [Economics];Trientine/ec [Economics];Trientine/tu [Therapeutic Use];0 (Chelating Agents);SJ76Y07H5F (Trientine),"Roberts, E. A.;Herder, M.;Hollis, A.",2015,Apr 07,https://dx.doi.org/10.1503/cmaj.140308,0,0,
101,Laser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease,"Wilson's disease is an autosomal recessive disorder in which the liver does not properly release copper into bile, resulting in prominent copper accumulation in various tissues. Affected patients suffer from hepatic disorders and severe neurological defects. Experimental studies in mutant mice in which the copper-transporting ATPase gene (Atp7b) is disrupted revealed a drastic, time-dependent accumulation of hepatic copper that is accompanied by formation of regenerative nodes resembling cirrhosis. Therefore, these mice represent an excellent exploratory model for Wilson's disease. However, the precise time course in hepatic copper accumulation and its impact on other trace metals within the liver is yet poorly understood. We have recently established novel laser ablation inductively coupled plasma mass spectrometry protocols allowing quantitative metal imaging in human and murine liver tissue with high sensitivity, spatial resolution, specificity and quantification ability. By use of these techniques, we here aimed to comparatively analyse hepatic metal content in wild-type and Atp7b deficient mice during ageing. We demonstrate that the age-dependent accumulation of hepatic copper is strictly associated with a simultaneous increase in iron and zinc, while the intrahepatic concentration and distribution of other metals or metalloids is not affected. The same findings were obtained in well-defined human liver samples that were obtained from patients suffering from Wilson's disease. We conclude that in Wilson's disease the imbalances of hepatic copper during ageing are closely correlated with alterations in intrahepatic iron and zinc content. Copyright © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.","Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Adolescent;Animals;Base Sequence;Blotting, Western;Cation Transport Proteins/ge [Genetics];Cation Transport Proteins/me [Metabolism];Copper/me [Metabolism];DNA Mutational Analysis;Diagnostic Imaging/mt [Methods];Disease Models, Animal;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Interleukin-1beta/ge [Genetics];Interleukin-1beta/me [Metabolism];Iron/me [Metabolism];*Laser Therapy;Liver/me [Metabolism];Liver/pa [Pathology];Male;*Mass Spectrometry/mt [Methods];*Metals/me [Metabolism];Mice, 129 Strain;Mice, Knockout;Reverse Transcriptase Polymerase Chain Reaction;Tissue Inhibitor of Metalloproteinase-1/ge [Genetics];Tissue Inhibitor of Metalloproteinase-1/me [Metabolism];Young Adult;Zinc/me [Metabolism];0 (Cation Transport Proteins);0 (Interleukin-1beta);0 (Metals);0 (Tissue Inhibitor of Metalloproteinase-1);789U1901C5 (Copper);E1UOL152H7 (Iron);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc)","Boaru, S. G.;Merle, U.;Uerlings, R.;Zimmermann, A.;Flechtenmacher, C.;Willheim, C.;Eder, E.;Ferenci, P.;Stremmel, W.;Weiskirchen, R.",2015,Apr,https://dx.doi.org/10.1111/jcmm.12497,0,0,
102,Bone demineralisation in a large cohort of Wilson disease patients,"AIMS AND BACKGROUND: We compared the bone mineral density (BMD) of adult Wilson disease (WD) patients (n=148), with an age- and gender-matched healthy control population (n=148). Within the WD cohort, correlations of BMD with WD disease parameters, lab results, type of treatment and known osteoporosis risk factors were analysed. METHODS: Hip and lumbar spine absolute BMD and T-score were measured by dual-energy X-ray absorptiometry. Osteoporosis and osteopenia were defined as a T-score<=-2.5, and between -1 and -2.5, respectively. RESULTS: There were significantly more subjects with abnormal T-scores in the WD population (58.8%) than in the control population (45.3%) (chi(2)=6.65, df=2, p=0.036), as there were 50.0% osteopenic and 8.8% osteoporotic WD patients, vs. 41.2% and 4.1%, respectively, in the controls. Especially L2-L4 spine BMD measurements (BMD and T-scores) differed significantly between the WD population and matched controls. L2-L4 spine BMD for WD patients was on average 0.054 g/cm(2) (5.1%) lower than in matched normal controls (0.995+/-0.156 vs 1.050+/-0.135; p=0.002). We found no significant correlation between BMD values and any of the WD disease parameters (e.g. the severity of liver disease), lab results, type of treatment or known osteoporosis risk factors. Duration of D-penicillamine treatment was negatively correlated with femoral BMD value, but in a clinically irrelevant manner, compared to age and gender. Importantly, BMD remained significantly lower in WD patients (n=89) vs. controls after excluding WD patients with cirrhosis (p=0.009). CONCLUSIONS: Our study suggests that WD is intrinsically associated with bone demineralisation.","Absorptiometry, Photon/mt [Methods];Adolescent;Adult;Aged;Bone Demineralization, Pathologic/dg [Diagnostic Imaging];Bone Demineralization, Pathologic/ep [Epidemiology];*Bone Demineralization, Pathologic/et [Etiology];Bone Density;Bone Diseases, Metabolic/dg [Diagnostic Imaging];Bone Diseases, Metabolic/ep [Epidemiology];Cohort Studies;Female;Femur Neck;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/ep [Epidemiology];Humans;Lumbar Vertebrae;Male;Middle Aged;Osteoporosis/dg [Diagnostic Imaging];Osteoporosis/ep [Epidemiology];Risk Factors;Young Adult","Weiss, K. H.;Van de Moortele, M.;Gotthardt, D. N.;Pfeiffenberger, J.;Seessle, J.;Ullrich, E.;Gielen, E.;Borghs, H.;Adriaens, E.;Stremmel, W.;Meersseman, W.;Boonen, S.;Cassiman, D.",2015,Sep,https://dx.doi.org/10.1007/s10545-015-9815-y,0,0,
103,Selective ion exchange governed by the Irving-Williams series in K2Zn3[Fe(CN)6]2 nanoparticles: toward a designer prodrug for Wilson's disease,"The principle of the Irving-Williams series is applied to the design of a novel prodrug based on K2Zn3[Fe(CN)6]2 nanoparticles (ZnPB NPs) for Wilson's disease (WD), a rare but fatal genetic disorder characterized by the accumulation of excess copper in the liver and other vital organs. The predetermined ion-exchange reaction rather than chelation between ZnPB NPs and copper ions leads to high selectivity of such NPs for copper in the presence of the other endogenous metal ions. Furthermore, ZnPB NPs are highly water-dispersible and noncytotoxic and can be readily internalized by cells to target intracellular copper ions for selective copper detoxification, suggesting their potential application as a new-generation treatment for WD.",Coordination Complexes/cs [Chemical Synthesis];Coordination Complexes/ch [Chemistry];*Coordination Complexes/tu [Therapeutic Use];Copper/me [Metabolism];Ferrocyanides/ch [Chemistry];HeLa Cells;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Ions/ch [Chemistry];Kinetics;*Nanoparticles/ch [Chemistry];Particle Size;Potassium/ch [Chemistry];Prodrugs/cs [Chemical Synthesis];Prodrugs/ch [Chemistry];*Prodrugs/tu [Therapeutic Use];Surface Properties;Zinc/ch [Chemistry];0 (Coordination Complexes);0 (Ferrocyanides);0 (Ions);0 (Prodrugs);789U1901C5 (Copper);J41CSQ7QDS (Zinc);RWP5GA015D (Potassium),"Kandanapitiye, M. S.;Wang, F. J.;Valley, B.;Gunathilake, C.;Jaroniec, M.;Huang, S. D.",2015,Feb 16,https://dx.doi.org/10.1021/ic502957d,0,0,
104,[Stimulated urinary copper excretion in the diagnosis of Wilson's disease],,Ceruloplasmin;*Copper;*Hepatolenticular Degeneration/di [Diagnosis];Humans;Liver/me [Metabolism];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Lopez-Sanroman, A.;Foruny, J. R.;Camarero, C.;Boixeda, D.",2015,Aug-Sep,https://dx.doi.org/10.1016/j.gastrohep.2014.12.005,0,0,
105,Wilson's disease in association with anetoderma,"BACKGROUND: Wilson's disease is an autosomal recessive disorder of copper homeostasis with predominantly hepatic and neuropsychiatric involvement. Anetoderma is a rare benign condition with focal damage of dermal elastic tissue. Previous reports described this skin disorder in association with prolonged D-Penicillamine therapy. CASE PRESENTATION: A 26-year-old male was referred for evaluation of asymptomatic elevation of aminotransferase levels. Investigations showed negative markers for chronic viral and autoimmune hepatitis, low ceruloplasmin level, and increased copper urinary excretion. Liver biopsy revealed chronic hepatitis with moderate activity and severe bridging fibrosis. Mutation analysis found a compound heterozygote genotype and supported a diagnosis of Wilson's disease. At the time of the primary physical exam, skin lesions were also observed, consisting of numerous white to pale papules less than 7-8 mm in diameter with central protrusion located at the upper part of the body. Primary anetoderma was established based on presentation and skin biopsy findings. Therapy with D-Penicillamine at a daily dose of 1500 mg was started, and, during 12-month follow-up, aminotransferase decreased to normal and skin lesions remained unchanged. CONCLUSION: In our opinion the case is a first reported association between Wilson's disease and primary anetoderma. The possible mechanism behind this relationship is discussed.",Adult;*Anetoderma/co [Complications];Anetoderma/pa [Pathology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/pa [Pathology];Humans;Male,"Ivanova, II;Kotzev, I. A.;Atanassova, M. V.;Gancheva, D. T.;Pavlov, S. I.;Krasnaliev, I. J.;Konstantinova, D. H.",2015,Feb,https://dx.doi.org/10.1007/s12328-015-0550-6,0,0,
106,"Wilson disease: a matter of copper, but also of zinc",,*Adenosine Triphosphatases/ge [Genetics];*Cation Transport Proteins/ge [Genetics];*Copper/me [Metabolism];*Deficiency Diseases/ge [Genetics];*Hepatolenticular Degeneration/pa [Pathology];Humans;Male;*Mutation;*Zinc/df [Deficiency];0 (Cation Transport Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);J41CSQ7QDS (Zinc),"Iorio, R.;Ranucci, G.",2015,Apr,https://dx.doi.org/10.1097/MPG.0000000000000725,0,0,
107,Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease,"BACKGROUND: Wilson disease requires lifelong therapy, currently given daily in multiple divided dosages. AIM: To prospectively evaluate once-daily trientine as therapy for Wilson disease. Methods: STUDY GROUP: eight patients (seven males) aged 22-71 years with stable Wilson disease treated from 4 to 50 years. Patients were monitored for 3 months then for 12 months on a single daily dose of trientine (15 mg/kg). RESULTS: All patients remained clinically well. ALT and AST fluctuated in some, but none required treatment stoppages or side effects. Liver synthetic function was unchanged. Mean 24-h urine copper and zinc excretions at end of treatment were 313.4 +/- 191.7 and 2,214 +/- 1,346 mug, respectively. CONCLUSIONS: Once-daily trientine should be explored further for possible maintenance therapy for WD. Single daily dose may improve adherence to therapy. Larger trials and longer-term follow-up will establish the safety and treatment efficacy of this once-daily treatment regimen for WD (registration: NCT01472874).","Administration, Oral;Adult;Aged;*Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Drug Administration Schedule;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Medication Adherence;Middle Aged;Patient Dropouts;Patient Satisfaction;Pilot Projects;Prospective Studies;Surveys and Questionnaires;Time Factors;Treatment Outcome;*Trientine/ad [Administration & Dosage];Trientine/ae [Adverse Effects];Young Adult;0 (Chelating Agents);SJ76Y07H5F (Trientine)","Ala, A.;Aliu, E.;Schilsky, M. L.",2015,May,https://dx.doi.org/10.1007/s10620-014-3495-6,0,0,
108,Detection of D-penicillamine in skin lesions in a case of dermal elastosis after a previous long-term treatment for Wilson's disease,"BACKGROUND: Skin adverse events associated with D-Penicillamine (DPA) are common and multi-faceted, although the presence of DPA or its metabolites has never been documented in the skin, because of inherent difficulties in determining its tissue levels. Thus, the association between DPA and DPA-related dermatoses has been only hypothesized on the basis of careful history, clinical observation and typical histopathological findings. OBJECTIVE: To detect DPA in biopsy specimens in a unique case of 25-year-late-onset elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum associated with a history of long-term high dose DPA, by applying a recently described analytical method to assess the presence of DPA in skin. METHODS: We used a reliable analytical method based on high-performance liquid chromatography coupled with amperometric detection to look for the presence of DPA in skin biopsy specimens. RESULTS: A chromatographic peak corresponding to DPA was evidenced in some affected skin samples collected from the patient. CONCLUSION: We documented the effective presence and the persistence after 25 years of DPA in the skin of a woman affected by elastotic cutaneous change due to a long-term therapy with DPA. This report provides further evidence of the relationship between DPA deposit in affected skin and clinical manifestation. Copyright © 2014 European Academy of Dermatology and Venereology.",*Chelating Agents/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Middle Aged;Penicillamine/ae [Adverse Effects];*Penicillamine/me [Metabolism];Penicillamine/tu [Therapeutic Use];*Skin Diseases/ci [Chemically Induced];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Neri, I.;Gurioli, C.;Raggi, M. A.;Saracino, M. A.;Morganti, E.;Bugamelli, F.;de Ponti, F.;Vaccari, S.;Patrizi, A.;Balestri, R.",2015,Feb,https://dx.doi.org/10.1111/jdv.12357,0,0,
109,A case of Wilson's disease with characteristic laparoscopic findings,"A 44-year-old male was pointed out liver function abnormality by medical check-up. Blood examination and computed tomography showed liver cirrhosis. Then, he was referred to our hospital for further examination. After blood test, viral markers revealed previous infection of hepatitis B virus (HBV). We estimated the etiology of his liver disease as previous HBV infection. On laparoscopic examination, his liver surface was nodular with mixed yellowish nodules and ash gray to copper-colored nodules in the diameter of 3-10 mm. There were large regenerative nodules in segments 3 and 4. Large regenerative nodules and irregular steatosis were contradictory to HBV-related liver cirrhosis, so then we supposed Wilson's disease. The amount of copper excretion in the urine was 326.6 mug (>100 mug/24 h). After D-penicillamine administration, urinary copper excretion increased to 2151.5 mug/24 h. Though hepatic copper concentration was 174.5 mug/g wet tissue (>200 mug/g wet tissue), his laboratory data fulfilled the Leipzig diagnostic criteria proposed by EASL. Laparoscopic examination with liver biopsy has advantages to survey many disease-specific findings on liver surface and to obtain adequate liver sample. Laparoscopic examination is one of the effective procedures for diagnosing relatively rare liver disease like Wilson's disease.",Adult;*Hepatolenticular Degeneration/pa [Pathology];Humans;*Laparoscopy;Male,"Muro, S.;Yasunaka, T.;Wada, N.;Morimoto, Y.;Ikeda, F.;Shiraha, H.;Takaki, A.;Noso, K.;Iwasaki, H.;Yamamoto, K.",2014,Apr,https://dx.doi.org/10.1007/s12328-014-0465-7,0,0,
110,"Atypical case of Wilson's disease with psychotic onset, low 24 hour urine copper and the absence of Kayser-Fleischer rings","INTRODUCTION: Wilson's disease is typically manifested in two clinical forms, neurological and hepatic and in rare cases it starts with psychiatric symptoms exclusively. We presented a rare atypical case of Wilson's disease with psy- chotic onset. CASE REPORT: A 22-year-old male patient was initially presented with predominant signs and symptoms of psychiatric disorder and then later with the development of neurological signs and symptoms. Neuroimaging, detected metal deposits in central nervous system (CNS) but not in peripheral organs, while serum analysis excluded pantothenate-kinase associated neurodegeneration and aceruloplasminemia. In favor of the diagnosis of Wilson's disease there were reduced concentrations of copper and ceruloplasmin concentrations and metal deposits in CNS, but other pathognomonic signs and symptoms were absent: increased copper in urine, Kayser-Fleischer rings in Descemet's corneal membrane and deposits of copper in liver. Introduction of penicillamine treatment resulted in improvement in mental and general health of the patient. Molecular genetic analysis definitely confirmed the diagnosis of Wilson's disease. CONCLUSION: Wilson's disease can remain undetected for a long period of time if masked with dominant or exclusive psychiatric symptoms. If clear clinical symptoms and signs, and unambiguous laboratory findings are not present, it is necessary to perform molecular genetic analysis to confirm the definitive diagnosis.","Biomarkers/ur [Urine];Chelating Agents/tu [Therapeutic Use];Copper/ur [Urine];Diagnosis, Differential;Diagnostic Imaging;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/px [Psychology];Humans;Male;Penicillamine/tu [Therapeutic Use];*Psychotic Disorders/di [Diagnosis];Psychotic Disorders/ge [Genetics];Young Adult;0 (Biomarkers);0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Krstic, D.;Antonijevic, J.;Spiric, Z.",2014,Dec,,0,0,
111,Epileptic status immediately after initiation of D-penicillamine therapy in a patient with Wilson's disease,,Adult;*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Female;*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Status Epilepticus/ci [Chemically Induced];Status Epilepticus/co [Complications];Status Epilepticus/dt [Drug Therapy];Treatment Outcome;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Berger, B.;Mader, I.;Damjanovic, K.;Niesen, W. D.;Stich, O.",2014,Dec,https://dx.doi.org/10.1016/j.clineuro.2014.09.030,0,0,
112,Impact of the discovery of human zinc deficiency on health,"The essentiality of zinc in humans was established in 1963. During the past 50y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. Growth retardation; cell-mediated immune dysfunction, and cognitive impairment are major clinical effects in human. At present we know of >300 enzymes and >1000 transcription factors that require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent. Zinc supplementation in the elderly results in decreased incidence of infections, decreased oxidative stress and decreased generation of inflammatory cytokines. Copyright © 2014 Elsevier GmbH. All rights reserved.",Dietary Supplements;Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Oxidative Stress/de [Drug Effects];Signal Transduction/de [Drug Effects];*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc),"Prasad, A. S.",2014,Oct,https://dx.doi.org/10.1016/j.jtemb.2014.09.002,0,0,
113,A severe case of esophageal ulcer causing a tight stricture despite long-term D-penicillamine treatment,"D-penicillamine has long been used in the management of rheumatic diseases due to the effects on inhibition of collagen synthesis. Herein, we report a severe case of esophageal ulcer causing a tight stricture extending through the distal esophagus despite the long-term D-penicillamine treatment in a patient with Wilson's disease. D-penicillamine would theoretically be expected to contribute to the healing of an esophageal ulcer. However, the drug failed to have a favorable outcome, which is notable and worth reporting.",Adult;Chelating Agents/ad [Administration & Dosage];*Esophageal Diseases/co [Complications];Esophageal Diseases/di [Diagnosis];*Esophageal Diseases/dt [Drug Therapy];Esophageal Stenosis/di [Diagnosis];*Esophageal Stenosis/et [Etiology];Esophageal Stenosis/pc [Prevention & Control];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Longitudinal Studies;Male;*Penicillamine/ad [Administration & Dosage];Treatment Failure;*Ulcer/co [Complications];Ulcer/di [Diagnosis];*Ulcer/dt [Drug Therapy];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Yapali, S.;Turan, I.;Ozutemiz, O.;Tekesin, O.",2014,Dec,https://dx.doi.org/10.1007/s00508-014-0610-9,0,0,
114,The promise of copper lowering therapy with tetrathiomolybdate in the cure of cancer and in the treatment of inflammatory disease,"Tetrathiomolybdate (TM) is a unique anticopper drug developed for the treatment of the neurologic presentation of Wilson's disease, for which it is excellent. Since it was known copper was required for angiogenesis, TM was tested on mouse cancer models to see if it would inhibit tumor growth based on an antiangiogenic effect. TM was extremely effective in these models, but all the tumors in the models started small in size - micrometastatic in size. Later, TM was tested in numerous human cancer trials, where it showed only modest effects. However, the mouse lesson of efficacy against micro disease was forgotten - all the trials were against bulky, advanced cancer. Now, the mouse evidence is coming back to life. Three groups are curing, or having major efficacy of TM, against advanced human cancers, heretofore virtually incurable, particularly if the cancer has been reduced to no evidence of disease (NED) status by conventional therapy. In that situation, where the remaining disease is micrometastatic, TM therapy appears to be curative. We have designed and initiated a study of TM in canine osteosarcoma at the micrometastatic phase to help put these findings on a firm scientific basis. TM also has major anti-inflammatory properties by inhibiting copper dependent cytokines involved in inflammation. This anti-inflammatory effect may be involved in TM's anticancer effect because cancers, as they advance, attract inflammatory cells that provide a plethora of additional proangiogenic agents. Copyright © 2014 Elsevier GmbH. All rights reserved.",Animals;Clinical Trials as Topic;*Copper/bl [Blood];Dogs;Humans;Inflammation/bl [Blood];*Inflammation/dt [Drug Therapy];*Molybdenum/tu [Therapeutic Use];Neoplasms/bl [Blood];*Neoplasms/dt [Drug Therapy];Osteosarcoma/bl [Blood];Osteosarcoma/dt [Drug Therapy];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Brewer, G. J.",2014,Oct,https://dx.doi.org/10.1016/j.jtemb.2014.07.015,0,0,
115,Penicillamine challenge test in the diagnosis of Wilson's disease,"Wilson's disease (WD) is one of the most common metabolic liver diseases encountered in children. Early diagnosis of the disease is essential because specific treatment can be offered, that will prevent further hepatocellular injury and neurologic complications. There is no single diagnostic test that can exclude or confirm the disease with certainty. Penicillamine challenge has proved itself to be a useful diagnostic test in the detection of WD. The main purpose of this study was to observe the reliability of penicillamine challenge test, in the diagnosis of WD. The cross sectional study was done with a case control design in the department of paediatric gastroenterology & Nutrition, BSMMU, Dhaka. The study was carried out on 60 patients of CLD. Along with other physical findings and laboratory investigations, 24 hours urinary copper excretions were estimated before and after penicillamine challenge. Study results were analyzed statistically. Thirty CLD patients who fulfilled the inclusion and exclusion criteria of WD were considered as cases (Group I) and remaining 30 CLD patients were considered as non-Wilsonian CLD and was labeled as control (Group II). Among the control group, 12 CLD patients were found to be HBsAg positive, 1 had hepatitis-C virus infection, 1 had autoimmune hepatitis and the remaining 16 CLD patients were Cryptogenic. The (mean+/-SD) age of WD patients was 9.90+/-28 years; male female ratio was 1.5:1. Most common presentation was ascites (70%). K-F ring was found in 86.7% cases. Serum ceruloplasmin level was found significantly lower in WD patients (mean+/-SD, 0.1197+/-23g/L, p<0.001). Baseline urinary copper excretion of WD patients differed significantly from controls (Median 219.0mug/24hour, range 35-2018mug/24hour, versus median 44mug/24hour, range 20-238mug/24hour, p<0.001). Baseline urinary copper excretion above 100mug/24hour was observed in 80% WD patients whereas it was 10% in controls. post penicillamine urinary copper excretion was significantly greater in WD patients than controls (Median 2635mug/24hour, range 648-6222mug/24hour, versus median 423mug/24hour, range 91-1250mug/24hour, p<0.001). Post penicillamine urinary copper above 1600mug/24hour observed in 70% of WD patients whereas not a single patient reached the value in control group. Twenty four hours urinary copper estimation after penicillamine challenge was found to be a valuable test in the diagnosis of WD.","Adolescent;Ceruloplasmin/an [Analysis];Child;Child, Preschool;Copper/ur [Urine];Cross-Sectional Studies;Female;*Hepatolenticular Degeneration/di [Diagnosis];Humans;Male;*Penicillamine;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Mazumder, M. W.;Karim, M. B.;Rukunuzzaman, M.",2014,Jul,,0,0,
116,Metalloproteomics: focus on metabolic issues relating to metals,"PURPOSE OF REVIEW: By determining metalloproteomes via high-throughput methodology, metalloproteomics provides a research strategy for investigating nutritional and metabolic issues relating to metals. In this review, we examine recent developments in metalloproteomics since its early days approximately 12 years ago, when we utilized metalloproteomics to investigate copper disposition in hepatocytes in relation to Wilson disease. RECENT FINDINGS: A metalloproteome is the set of proteins that have metal-binding capacity by being metalloproteins or manifesting metal-binding sites. Like all proteomes, a metalloproteome is determined within the context of a well defined system. It can be ascertained for a single metal or multiple metals in that system. Apart from major technological advances in analytical techniques, recent work has examined metalloproteomes for metals other than copper, notably nickel, zinc and manganese. Given the importance of microbiomes to metabolism, microbial metalloproteomics is a rapidly expanding and promising new field. SUMMARY: Metals play key roles in metabolic processes. Sufficient technological progress has taken place in the past decade to make metalloproteomics an exciting and innovative type of research in nutrition and metabolism. It elucidates how metals contribute to metabolic physiology across the phyla, including in microbes. For humans, it may clarify mechanisms as well as identify informative diagnostic or prognostic biomarkers.",Humans;*Metalloproteins/me [Metabolism];*Metals/me [Metabolism];*Proteome/me [Metabolism];0 (Metalloproteins);0 (Metals);0 (Proteome),"Roberts, E. A.;Sarkar, B.",2014,Sep,https://dx.doi.org/10.1097/MCO.0000000000000085,0,0,
117,Symptomatic copper deficiency in three Wilson's disease patients treated with zinc sulphate,"Wilson's disease (WD) is caused by excess of copper that leads to accumulation of copper mainly in the liver, brain and needs life-long decoppering therapy. However, overtreatment with anti-copper agents may lead to copper deficiency which may cause neurological and hematological symptoms. Copper is an important cofactor for many enzymes. This report describes three WD patients with diagnosed copper deficiency during zinc sulphate (ZS) treatment. After 5-16 years of therapy all patients developed leucopenia. Spinal cord injury was manifested in two of the patients. One of them also presented myopathy. In conclusion, copper deficiency may occur in different time after treatment onset, therefore regular copper metabolism and hematological monitoring is necessary. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.",Adolescent;Adult;*Copper/df [Deficiency];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Magnetic Resonance Imaging;Middle Aged;Spinal Cord/pa [Pathology];*Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper),"Dziezyc, K.;Litwin, T.;Sobanska, A.;Czlonkowska, A.",2014,,https://dx.doi.org/10.1016/j.pjnns.2014.05.002,0,0,
118,Epidermolysis bullosa acquisita-like eruption with anticollagen VII autoantibodies induced by D-penicillamine in Wilson disease,,Adult;Autoantibodies/im [Immunology];*Chelating Agents/ae [Adverse Effects];Collagen Type VII/im [Immunology];*Drug Eruptions/et [Etiology];*Epidermolysis Bullosa Acquisita/ci [Chemically Induced];Epidermolysis Bullosa Acquisita/im [Immunology];Epidermolysis Bullosa Acquisita/pa [Pathology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];0 (Autoantibodies);0 (Chelating Agents);0 (Collagen Type VII);GNN1DV99GX (Penicillamine),"Ingen-Housz-Oro, S.;Grootenboer-Mignot, S.;Ortonne, N.;Nahon, S.;Horvath, J.;Bernardeschi, C.;Laffitte, E.;Andre, C.;Chollet-Martin, S.;Wolkenstein, P.;Chosidow, O.",2014,Dec,https://dx.doi.org/10.1111/bjd.13153,0,0,
119,Bone mineralization in children with Wilson's disease,"BACKGROUND: The goal of this study was to determine bone mineralization in children with Wilson's disease (WD). METHODS: Twenty-seven patients (16 males) and two age- and gender-matched healthy children for each patient were enrolled in the study. Bone mineral content (BMC, grams) and density (BMD, g/cm(2)) at lumbar 1-4 vertebrae were measured by dual-energy X-ray absorptiometry. Urinary calcium excretion was calculated in 19 patients. The effect of cirrhosis and hypercalciuria on BMC and BMD was also evaluated in WD patients. RESULTS: There was no statistically significant difference between patients and healthy controls regarding mean BMC (33.0+/-13.9 vs. 35.8+/-13.8 g) (p=0.940) and mean BMD values (0.66+/-0.16 vs. 0.71+/-0.18 g/cm(2)) (p=0.269), respectively. Nine (47.4 %) patients had hypercalciuria. Hypercalciuric patients had statistically significant lower BMC and BMD values than those without hypercalciuria. A significant difference continued to be present after age, weight, height, and pubertal stage adjustment was done, but disappeared after weight, height, follow up duration, and pubertal stage adjustment was done. The presence of cirrhosis did not affect BMC and BMD significantly in WD patients. CONCLUSIONS: BMC and BMD in children with WD were normal. The presence of hypercalciuria but not cirrhosis may affect BMC and BMD negatively in the patients.","Absorptiometry, Photon;Adolescent;Biomarkers/me [Metabolism];*Bone Density;*Calcification, Physiologic;Calcium/ad [Administration & Dosage];Calcium/ur [Urine];Child;Child, Preschool;Cross-Sectional Studies;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Hypercalciuria;Liver Cirrhosis/me [Metabolism];Lumbar Vertebrae/me [Metabolism];Male;Zinc/ad [Administration & Dosage];0 (Biomarkers);J41CSQ7QDS (Zinc);SY7Q814VUP (Calcium)","Cetinkaya, A.;Ozen, H.;Yuce, A.;Saltik-Temizel, I. N.;Demir, H.;Gurakan, F.",2014,Sep,https://dx.doi.org/10.1007/s12664-014-0468-9,0,0,
120,[Wilson Disease],,Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/th [Therapy];Humans;Magnetic Resonance Imaging;Penicillamine/tu [Therapeutic Use];Trace Elements/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),Anonymous,2014,Apr,,0,0,
121,Liver transplantation for Wilson's disease,"Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ~5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors. Copyright © 2014 New York Academy of Sciences.","End Stage Liver Disease/et [Etiology];End Stage Liver Disease/su [Surgery];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/su [Surgery];Humans;Liver Failure, Acute/et [Etiology];Liver Failure, Acute/su [Surgery];Liver Transplantation/mt [Methods];*Liver Transplantation;Living Donors;Treatment Outcome","Schilsky, M. L.",2014,May,https://dx.doi.org/10.1111/nyas.12454,0,0,
122,Wilson's disease,"Wilson's disease (WD) is a disorder of copper transport resulting from the defective function of a copper transporting P-type ATPase, ATP7B. The WD incidence is approximately 1/50-10,000 live births worldwide. Clinical manifestations of WD may be of any kind, but usually the symptoms of presentation are hepatic or neuropsychiatric, with a vast range of disturbances for both groups of symptoms. In children, however, clinical symptoms may be absent, making the diagnosis of the disease more difficult than in adults. Hepatic manifestations may range from asymptomatic minor biochemical disturbances, to acute, but mostly chronic, hepatitis, cirrhosis or severe fulminant hepatic failure. The spectrum of neurological manifestations is wide, including tremor, hypersalivation, Dysarthria, coordination defects, dystonia, ataxia. The spectrum of psychiatric manifestations is considerable and may include different disturbances such as altered working performance, anxiety, depression and antisocial behaviour. Kayser-Fleischer rings (KF) are present in 95% of patients with neurological symptoms and somewhat over half of those without neurological symptoms. In children presenting with liver disease, KF rings are usually absent. To obtain a more reliable diagnosis of WD, the Leipzig scoring system was proposed by an international consensus of experts. Wilson's disease copper overload is treated with chelating agents such as penicillamine, trientine and tetrathiomolybdate. Zinc is used mostly for mantainance therapy or the treatment of asymptomatic WD patients.",*Disease Management;*Genetic Predisposition to Disease;*Genetic Testing/mt [Methods];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans,"Loudianos, G.;Lepori, M. B.;Mameli, E.;Dessi, V.;Zappu, A.",2014,,,0,0,
123,D-Penicillamine tripodal derivatives as efficient copper(I) chelators,"New tripodal metal-chelating agents derived from nitrilotriacetic acid (NTA) and extended by three unnatural amino acids D-penicillamine (D-Pen) are presented. D-Pen is actually the drug most extensively used to treat copper (Cu) overload in Wilson's disease and as such is a very attractive building block for the design of chelating agents. D-Pen is also a bulkier analogue of cysteine, with the beta-methylene hydrogen atoms replaced by larger methyl groups. The hindrance of the gem-dimethyl group close to the thiol functions is demonstrated to influence the speciation and stability of the metal complexes. The ligands L(4) (ester) and L(5) (amide) were obtained from NTA and commercial D-Pen synthons in four and five steps with overall yields of 14 and 24%, respectively. Their ability to bind Cu(I), thanks to their three thiolate functions, has been investigated using both spectroscopic and analytical methods. UV, CD, and NMR spectroscopy and mass spectrometry evidence the formation of two Cu(I) complexes with L(5): the mononuclear complex CuL(5) and one cluster (Cu2L(5))2. In contrast, the bulkier ethyl ester derivative L(4) cannot accommodate the mononuclear complex in solution and thus forms exclusively the cluster (Cu2L(4))2. Cu K-edge X-ray absorption spectroscopy (XAS and EXAFS) confirms that Cu(I) is bound in trigonal-planar sulfur-only environments in all of these complexes with Cu---S distances ranging from 2.22 to 2.23 A. Such C3-symmetric CuS3 cores are coordination modes frequently adopted in Cu(I) proteins such as metallothioneins. These two ligands bind Cu(I) tightly and selectively, which makes them promising chelators for intracellular copper detoxification in vivo.",*Chelating Agents/cs [Chemical Synthesis];Chelating Agents/ch [Chemistry];*Copper/ch [Chemistry];Molecular Structure;Nitrilotriacetic Acid/ch [Chemistry];*Organometallic Compounds/cs [Chemical Synthesis];Organometallic Compounds/ch [Chemistry];*Penicillamine/ch [Chemistry];0 (Chelating Agents);0 (Organometallic Compounds);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);KA90006V9D (Nitrilotriacetic Acid),"Jullien, A. S.;Gateau, C.;Lebrun, C.;Kieffer, I.;Testemale, D.;Delangle, P.",2014,May 19,https://dx.doi.org/10.1021/ic5004319,0,0,
124,Clinical considerations for an effective medical therapy in Wilson's disease,"Wilson's disease is an autosomal recessively inherited copper overload disorder that leads to hepatic and/or neurologic symptoms. More than a century after the first description of Wilson's disease, the available medical treatment options have not been standardized. The efficacy of the commonly used drugs is satisfactory for hepatic disease, but disappointing in the neurologic patients, including the risk of neurologic deterioration after the initiation of chelation therapy. An approach to overcome this problem is the careful and systematic assessment of biochemical response patterns and the quantitative monitoring of symptoms using validated rating scales. Standardized dosage strategies that address changes in copper pools might improve adherence and reduce side effects. Such an approach may reduce long-term morbidity. In this paper, we discuss considerations for an effective medical treatment and requirements for future studies in Wilson's disease. Copyright © 2014 New York Academy of Sciences.",Ceruloplasmin/me [Metabolism];Chelating Agents/ad [Administration & Dosage];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Copper/to [Toxicity];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Molybdenum/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Weiss, K. H.;Stremmel, W.",2014,May,https://dx.doi.org/10.1111/nyas.12437,0,0,
125,AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism,"MEDNIK (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia) syndrome has been recently described as a new disorder of copper metabolism. This multisystem disease combines clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver copper overload is treatable using zinc acetate therapy. MEDNIK syndrome is caused by mutation of the AP1S1 gene, which codes for the sigma1A subunit of adaptor protein complex 1, and directs intracellular trafficking of copper pumps ATP7A and ATP7B. Adaptor protein complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. A growing number of diseases have been associated with mutations in genes coding for adaptor protein complexes subunits and we propose for them the term adaptinopathies, as a new organic category of disorders of intracellular trafficking, which offers the opportunity to dissect the mechanisms involved in the crosstalk between the Golgi apparatus and the other organelles. Copyright © 2014 New York Academy of Sciences.","Adaptation, Biological;*Adaptor Protein Complex 1/ge [Genetics];*Adaptor Protein Complex sigma Subunits/ge [Genetics];Adaptor Proteins, Vesicular Transport/ge [Genetics];*Adenosine Triphosphatases/me [Metabolism];*Cation Transport Proteins/me [Metabolism];*Copper/me [Metabolism];*Hepatolenticular Degeneration/ge [Genetics];Humans;*Menkes Kinky Hair Syndrome/ge [Genetics];Protein Transport/ge [Genetics];Syndrome;Zinc Acetate/tu [Therapeutic Use];0 (AP1S1 protein, human);0 (Adaptor Protein Complex 1);0 (Adaptor Protein Complex sigma Subunits);0 (Adaptor Proteins, Vesicular Transport);0 (Cation Transport Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (ATP7A protein, human);EC 3-6-3-4 (Wilson disease protein);FM5526K07A (Zinc Acetate)","Martinelli, D.;Dionisi-Vici, C.",2014,May,https://dx.doi.org/10.1111/nyas.12426,0,0,
126,Wilson disease: what is still unclear in pediatric patients?,"Since Wilson disease (WD) may not be present with evident clinical symptoms of liver injury and neurological presentation is rare in children, establishing a diagnosis is often challenging, especially in childhood. Increased transaminases can be the only abnormality found in early course of WD. In clinical practice, high suspicion is crucial for early diagnosis and timely treatment to ensure better outcomes. Conventional diagnostic criteria established for adults are commonly agreed for children but may not always be appropriate in very young age. Currently, the best therapeutic approach for each specific presentation of the disease remains controversial and there are no clear indications about how to treat pediatric WD patients with a mild liver disease. Copyright © 2014 Elsevier Masson SAS. All rights reserved.",Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Child;Copper/an [Analysis];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver/ch [Chemistry];Trace Elements/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);J41CSQ7QDS (Zinc),"Ranucci, G.;Socha, P.;Iorio, R.",2014,Jun,https://dx.doi.org/10.1016/j.clinre.2014.03.002,0,0,
127,Elastosis perforans serpiginosa: a case of a penicillamine-induced degenerative dermatosis,,Aged;*Chelating Agents/ae [Adverse Effects];Cutis Laxa/ci [Chemically Induced];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;*Penicillamine/ae [Adverse Effects];*Skin Diseases/ci [Chemically Induced];Skin Diseases/pa [Pathology];0 (Chelating Agents);GNN1DV99GX (Penicillamine);Elastosis perforans serpiginosa,"Hellriegel, S.;Bertsch, H. P.;Emmert, S.;Schon, M. P.;Haenssle, H. A.",2014,Jul,https://dx.doi.org/10.1001/jamadermatol.2013.8635,0,0,
128,Population screening for Wilson's disease,"Wilson's disease is an autosomal recessive disorder of copper transport caused by mutations in the gene encoding an ATPase, ATP7B. Early detection of Wilson's disease is critical because effective medical treatments such as chelating agents and zinc salts are available, which can prevent lifelong neurological disabilities and/or cirrhosis. It is unfortunate that most patients are brought to our attention after they have developed serious complications such as brain damage or cirrhosis, despite the availability of effective treatments. The diagnosis is usually made through copper measurement in the liver tissue, followed by confirmation with genetic testing of the ATP7B gene. Currently, there are no effective biomarkers or methods suitable for newborn screening for Wilson's disease. Ceruloplasmin has been tested for pediatric and newborn screening with limited outcome. Recently, liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) has emerged as a robust technology that may enable multiplex quantification of signature proteotypic peptides with low abundance. The application of this technology may help facilitate the research on Wilson's disease for protein expression, biomarker study, diagnosis, and, hopefully, screening. Copyright © 2014 New York Academy of Sciences.","Adenosine Triphosphatases/bl [Blood];Adenosine Triphosphatases/ge [Genetics];Adolescent;Biomarkers/bl [Blood];Cation Transport Proteins/bl [Blood];Cation Transport Proteins/ge [Genetics];Ceruloplasmin/an [Analysis];Child;Child, Preschool;Chromatography, Liquid/mt [Methods];Clinical Trials as Topic;Copper/bl [Blood];Early Diagnosis;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Humans;Infant;Infant, Newborn;*Mass Screening/mt [Methods];Mass Spectrometry/mt [Methods];Neonatal Screening/mt [Methods];Peptide Fragments/bl [Blood];0 (Biomarkers);0 (Cation Transport Proteins);0 (Peptide Fragments);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Hahn, S. H.",2014,May,https://dx.doi.org/10.1111/nyas.12423,0,0,
129,The trientine crisis in Canada: a call to advocacy,,Canada;*Chelating Agents/ec [Economics];Chelating Agents/tu [Therapeutic Use];Consumer Advocacy;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Prescription Fees;*Trientine/ec [Economics];Trientine/tu [Therapeutic Use];0 (Chelating Agents);SJ76Y07H5F (Trientine),"Chandok, N.;Roberts, E. A.",2014,Apr,,0,0,
130,Zinc monotherapy is effective in Wilson's disease patients with mild liver disease diagnosed in childhood: a retrospective study,"BACKGROUND: Wilson's disease (WD) evolves rapidly and is fatal if untreated. The treatment of WD patients with mild liver disease is not clearly defined. To address this issue, we evaluated long-term outcomes of three treatment regimens (D-penicillamine, zinc or both) in patients diagnosed in childhood. METHODS: We retrospectively evaluated efficacy, compliance and reasons for treatment discontinuation in 42 WD patients (median age at diagnosis: 6 years; median follow-up: 12 years) with mild liver disease. Treatment duration for each treatment block until a medication change or completion of follow-up was analyzed. Events of change of treatment were evaluated using Kaplan-Meier analysis. RESULTS: Total discontinuations due to treatment failure or adverse events were more frequent in patients receiving D-penicillamine (45%) or combination (36%) therapy than in patients receiving zinc (12%) (P = .001 and P = .02, respectively). Treatment failure was more frequent on D-penicillamine (28%) and combination therapy (36%) than on zinc (12%); the difference was statistically significant only between zinc and combination therapy (P = .03). First-line zinc monotherapy controlled WD-related liver disease in 13/15 patients (87%); the two subjects that failed on zinc were poor adherent. Zinc was effective in 3/5 (60%) patients that failed on D-penicillamine and combination regimens. All 15 D-penicillamine responders that switched to zinc had good control of liver disease at a median follow-up of 13.1 years. Among 6 D-penicillamine non-responders that switched to zinc, 4 (67%) responded. At follow-up completion, only 5/42 (12%) patients failed. Adverse event-induced discontinuation was significantly more frequent in patients on D-penicillamine than in patients receiving zinc (P = .03). CONCLUSIONS: Zinc monotherapy is effective in controlling WD-related liver disease both as first-line and as maintenance treatment in patients with mild liver disease diagnosed in childhood.",Adenosine Triphosphatases;Cation Transport Proteins;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Diseases/dt [Drug Therapy];Male;Retrospective Studies;*Zinc/tu [Therapeutic Use];0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc),"Ranucci, G.;Di Dato, F.;Spagnuolo, M. I.;Vajro, P.;Iorio, R.",2014,Mar 25,https://dx.doi.org/10.1186/1750-1172-9-41,1,1,
131,Current status of human hepatocyte transplantation and its potential for Wilson's disease,"Wilson's disease (WD) is a genetic disorder of liver copper excretion leading to its accumulation in various vital organs like the liver, brain, and kidneys. Drugs such as penicillamine, trientine, and zinc salts are the mainstay of treatment, with good outcomes; but nonresponders or a lack of compliance to the drug treatment can result in disease progression and acute liver failure (ALF). Current treatment for WD with ALF is an emergency liver transplantation and lifelong immunosuppression. Human hepatocyte transplantation (HTx) is increasingly used as treatment for liver-based metabolic defects. HTx may benefit WD patients with ALF, either as transient support until chelation treatment shows its effect or as a definitive cure through liver repopulation by healthy donor cells, as shown in animal models of WD. Although clinical trials of HTx have already proven safety and efficacy in different ALF etiologies, it remains to be demonstrated similarly in cases of WD. Copyright © 2014 New York Academy of Sciences.","Animals;Cell Separation/mt [Methods];Cell Survival;Hepatocytes/cy [Cytology];Hepatocytes/ph [Physiology];*Hepatocytes/tr [Transplantation];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration/th [Therapy];Humans;Immunosuppression;Liver Failure, Acute/et [Etiology];Liver Failure, Acute/pa [Pathology];Liver Failure, Acute/th [Therapy]","Filippi, C.;Dhawan, A.",2014,May,https://dx.doi.org/10.1111/nyas.12386,0,0,
132,Acute hemolytic anemia as an initial presentation of Wilson disease in children,"BACKGROUND: Wilson disease (WD) is an inherited disorder of copper metabolism. Hemolytic anemia in WD occurs in up to 17% of patients at some point during their illness. AIM: To screen for WD among children presenting with hemolytic anemia. METHODOLOGY: Twenty cases (mean age, 8.8 +/- 3.9 y) with Coombs-negative hemolytic anemia, attending the hematology clinic of children hospital, Cairo University, were screened for WD by serum ceruloplasmin level, 24 hours urinary copper before and after D-penicillamine challenge test, and slit-lamp examination for detecting Kayser-Fleischer rings. RESULTS: No case had low ceruloplasmin, whereas bilateral Kayser-Fleischer rings was detected in 5% of our cases. Urinary copper was elevated in 5% before and in 40% after D-penicillamine challenge test. According to the scoring system used, 1 case had definite WD and 7 cases were likely to have WD. These 8 (40%) cases were referred to as group B. Group B had a significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocytes (P=0.04, 0.001, 0.04, and 0.04, respectively) and a significantly higher urinary copper after penicillamine (P=0.000) when compared with group A (unlikely WD). CONCLUSION: WD is not uncommon in children with hemolytic anemia after exclusion of other common causes.","Acute Disease;Adolescent;*Anemia, Hemolytic/di [Diagnosis];Anemia, Hemolytic/me [Metabolism];Ceruloplasmin/me [Metabolism];Chelating Agents/me [Metabolism];Child;Child, Preschool;Cohort Studies;Diagnosis, Differential;Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver Function Tests;Male;Penicillamine/me [Metabolism];Prognosis;0 (Chelating Agents);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","El Raziky, M. S.;Ali, A.;El Shahawy, A.;Hamdy, M. M.",2014,Apr,https://dx.doi.org/10.1097/MPH.0000000000000127,0,0,
133,Control of mania with chelation-only in a case of Wilson's disease,,*Bipolar Disorder/dt [Drug Therapy];*Bipolar Disorder/et [Etiology];*Chelation Therapy/mt [Methods];*Hepatolenticular Degeneration/co [Complications];Humans;Male;*Penicillamine/tu [Therapeutic Use];Trace Elements/tu [Therapeutic Use];Young Adult;Zinc/tu [Therapeutic Use];0 (Trace Elements);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Mitra, S.;Ray, A. K.;Roy, S.",2014,Winter,https://dx.doi.org/10.1176/appi.neuropsych.12110271,0,0,
134,D-penicillamine versus zinc sulfate as first-line therapy for Wilson's disease,"BACKGROUND AND PURPOSE: To compare the course of treatment in patients with symptomatic Wilson's disease (WD) receiving either D-penicillamine (DPA) or zinc sulfate (ZS) as first-line therapy. METHODS: In all, 143 consecutive patients diagnosed with symptomatic WD from January 2005 to December 2009, followed until December 2010, were included. The decision about first-line therapy was made individually after discussion with the patient. Physicians had no clear preference of one drug over the other. Data were analyzed in subgroups with predominantly neurological (DPA, 35; ZS, 21) and hepatic (DPA, 36; ZS, 51) presentation of WD. RESULTS: According to Kaplan-Meier analysis, neurological WD patients scheduled for DPA had a similar probability of not remaining on first-line therapy as patients receiving ZS (20% vs. 24% at the end of follow-up), with adjusted odds ratio (OR) of 0.9 (95% CI 0.2-3.5). In patients with hepatic WD, this probability was significantly higher for DPA (31% vs. 12%; adjusted OR 3.0, 95% CI 0.9-9.9), especially in the first 6 months. Early worsening occurred only in neurological WD patients, with no differences between both treatment groups (35% vs. 19%; OR 2.8, 95% CI 0.7-10.8). Neurological improvement and decrease of liver enzymes were achieved with similar frequency. Compliance with DPA was better in hepatic (97% vs. 80%) but not in neurological patients (91% vs. 81%). Drug adverse effects were more common on DPA (15% vs. 3%). CONCLUSIONS: DPA and ZS are effective in the majority of WD patients. Neither therapy appears to be clearly superior. Therefore ZS may be considered a reasonable alternative to DPA as a first-line therapy. Copyright © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.",Adult;*Antirheumatic Agents/tu [Therapeutic Use];Female;Follow-Up Studies;Hepatolenticular Degeneration/cl [Classification];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Kaplan-Meier Estimate;Male;Neurologic Examination;Odds Ratio;Patient Compliance;*Penicillamine/tu [Therapeutic Use];Probability;Retrospective Studies;Treatment Outcome;*Zinc Sulfate/tu [Therapeutic Use];0 (Antirheumatic Agents);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine),"Czlonkowska, A.;Litwin, T.;Karlinski, M.;Dziezyc, K.;Chabik, G.;Czerska, M.",2014,Apr,https://dx.doi.org/10.1111/ene.12348,1,1,
135,"Treatment with D-penicillamine or zinc sulphate affects copper metabolism and improves but not normalizes antioxidant capacity parameters in Wilson disease.[Erratum appears in Biometals. 2014 Feb;27(1):217 Note: Grazyna, Gromadzka [corrected to Gromadzka, Grazyna]; Agata, Karpinska [corrected to Karpinska, Agata]; Adam, Przybylkowski [corrected to Przybylkowski, Adam]; Tomasz, Litwin [corrected to Litwin, Tomasz]; Agata, Wierzchowska-Ciok [corrected to Wierzchowska-Ciok, Agata]; Karolina, Dziezyc [corrected to Dziezyc, Karolina]; Grzegorz, Chabik [corrected to Chabik, Grzegorz]; Anna, Czlonkowska [corrected to Czlonkowska, Anna]]","Copper accumulation in tissues due to a biallelic pathogenic mutation of the gene: ATP7B results in a clinical phenotype known as Wilson disease (WD). Aberrations in copper homeostasis can create favourable conditions for superoxide-yielding redox cycling and oxidative tissue damage. Drugs used in WD treatment aim to remove accumulated copper and normalise the free copper concentration in the blood. In the current study the effect of decoppering treatment on copper metabolism and systemic antioxidant capacity parameters was analyzed. Treatment naive WD patients (TNWD) (n = 33), those treated with anti-copper drugs (TWD) (n = 99), and healthy controls (n = 99) were studied. Both TNWD and TWD patients characterised with decreased copper metabolism parameters, as well as decreased total antioxidant potential (AOP), glutathione (GSH) level, activity of catalase, glutathione peroxidase (GPx), and S-transferase glutathione, compared to controls. TWD patients had significantly lower copper metabolism parameters, higher total AOP and higher levels of GSH than TWD individuals; however, no difference was observed between these two patient groups with respect to the rest of the antioxidant capacity parameters. Patients who had undergone treatment with D-penicillamine or zinc sulphate did not differ with respect to copper metabolism or antioxidant capacity parameters, with the exception of GPx that was lower in D-penicillamine treated individuals. These data suggest that anti-copper treatment affects copper metabolism as well as improves, but does not normalize, natural antioxidant capacity in patients with WD. We propose to undertake studies aimed to evaluate the usefulness of antioxidants as well as selenium as a supplemental therapy in WD.",Adult;*Antioxidants/me [Metabolism];*Copper/me [Metabolism];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];*Zinc Sulfate/pd [Pharmacology];Zinc Sulfate/tu [Therapeutic Use];0 (Antioxidants);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Gromadzka, G.;Karpinska, A.;Przybylkowski, A.;Litwin, T.;Wierzchowska-Ciok, A.;Dziezyc, K.;Chabik, G.;Czlonkowska, A.",2014,Feb,https://dx.doi.org/10.1007/s10534-013-9694-3,0,1,
136,Worsening of Wilson disease following penicillamine therapy,"BACKGROUND: Penicillamine is a standard therapy for Wilson disease (WD) but some patients have paradoxical worsening. Predictors of such deterioration have not been evaluated. This study documents frequency and predictors of deterioration following treatment in WD. METHODS: 59 consecutive patients with neurologic WD and 4 asymptomatic siblings were prospectively evaluated. Their clinical, laboratory, ultrasound abdomen and cranial MRI findings with and without worsening were compared. Patients were treated with oral penicillamine and/or zinc and followed up at 1, 3 and 6 months or earlier if needed. Deterioration was defined by >10% worsening in baseline Burke-Fahn-Marsden score or appearance of new neurological sign. RESULTS: Patients' median age was 13 years and 13 were females. 19 patients (30.2%) worsened following treatment; 10 within 1 month, 7 in 1-3 months, and 2 after 3 months of treatment. Deterioration was associated with drooling, leukopenia, thrombocytopenia, splenomegaly and evidence of chronic liver disease. None of the asymptomatic patients following zinc therapy deteriorated. CONCLUSIONS: In the deteriorating group, withdrawal of penicillamine resulted in improvement/stabilization in 11 patients, 2 improved by trientine therapy and 4 continued to deteriorate till 3 months. 30.2% patients with WD deteriorated following penicillamine, especially those with chronic liver disease, leukopenia and thrombocytopenia. Copyright © 2013 S. Karger AG, Basel.",Adolescent;*Chelating Agents/ae [Adverse Effects];Child;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];Treatment Outcome;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Kalita, J.;Kumar, V.;Chandra, S.;Kumar, B.;Misra, U. K.",2014,,https://dx.doi.org/10.1159/000355276,0,1,
137,Compliant treatment with anti-copper agents prevents clinically overt Wilson's disease in pre-symptomatic patients,"BACKGROUND AND PURPOSE: Wilson's disease (WD) is an inherited copper metabolism disorder that leads to dysfunction of affected tissues, mostly in the liver and brain. Anti-copper treatment should prevent clinically overt WD in pre-symptomatic patients but this has not been supported by strong evidence. Our aim was to evaluate the long-term effectiveness of treatment in clinically pre-symptomatic patients, with particular emphasis on patient compliance with treatment. METHODS: Data were analyzed for 87 consecutive patients with no clinical symptoms of WD who were identified between 1957 and 2009 by family screening. All of them since diagnosis were treated with either zinc sulphate (Zn) (66.7%) or D-penicillamine (DPA) (33.3%). RESULTS: During a median follow-up of 12 years (range 3-52), 55 (63%) patients remained without clinical symptoms, 13 (15%) developed neuropsychiatric symptoms and 21 (24%) developed hepatic dysfunction, including five deaths from hepatic failure. Non-compliance for at least three consecutive months was observed in 39 patients, and in 29 cases this extended for more than 12 months. Multivariate analysis showed that the odds of developing symptomatic WD were independently increased by non-compliance (odds ratio 24.0, 95% confidence interval 6.0-99.0). According to Kaplan-Meier analysis patients who were compliant to treatment had a significantly higher likelihood of remaining symptom-free, and their overall survival was similar to the survival rate observed in the general population. CONCLUSION: The use of anti-copper agents in clinically pre-symptomatic patients diagnosed with WD allows clinically overt disease to be effectively prevented. However, compliance with therapy is extremely important. Copyright © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.",Adolescent;Adult;*Chelating Agents/tu [Therapeutic Use];Child;Female;Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;Middle Aged;Patient Compliance;*Penicillamine/tu [Therapeutic Use];Survival Rate;Treatment Outcome;Young Adult;*Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine),"Dziezyc, K.;Karlinski, M.;Litwin, T.;Czlonkowska, A.",2014,Feb,https://dx.doi.org/10.1111/ene.12320,0,1,
138,Mowat-Wilson syndrome: deafness in the first Egyptian case who was conceived by intracytoplasmic sperm injection,"Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects. The prevalence of Mowat-Wilson syndrome is currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed, particularly in patients without Hirschsprung disease. We report here the first Egyptian case of Mowat-Wilson syndrome who was conceived by intracytoplasmic sperm injection. The patient manifested bilateral sensorineural hearing loss--a new feature not previously reported in cases of Mowat-Wilson syndrome. This report describes the first Egyptian patient of Mowat-Wilson syndrome who was conceived after intracytoplasmic sperm injection, and provides a new evidence for the inclusion of deafness among the congenital defects of the syndrome. Copyright © The Author(s) 2013.","Child, Preschool;*Deafness/et [Etiology];Egypt;Facies;Female;*Hirschsprung Disease/co [Complications];*Hirschsprung Disease/et [Etiology];Humans;*Intellectual Disability/co [Complications];*Intellectual Disability/et [Etiology];*Microcephaly/co [Complications];*Microcephaly/et [Etiology];*Sperm Injections, Intracytoplasmic/ae [Adverse Effects];Mowat-Wilson syndrome","Abdalla, E. M.;Zayed, L. H.",2014,Dec,https://dx.doi.org/10.1177/0883073813509120,0,0,
139,Metal storage disorders: Wilson disease and hemochromatosis,"Hereditary hemochromatosis and Wilson disease are autosomal recessive storage disorders of iron and copper overload, respectively. These metals are involved in multiple redox reactions, and their abnormal accumulation can cause significant injury in the liver and other organs. Over the last few decades clinicians have developed a much better understanding of these metals and their mechanism of action. Moreover, sophisticated molecular genetic testing techniques that make diagnostic testing less invasive are now available. This article updates and discusses the pathogenesis, diagnosis, and management of these metal storage disorders. Copyright © 2014 Elsevier Inc. All rights reserved.",Biopsy;*Chelating Agents/tu [Therapeutic Use];Disease Progression;Genetic Predisposition to Disease;Genetic Testing;Hemochromatosis/bl [Blood];Hemochromatosis/ge [Genetics];Hemochromatosis/pa [Pathology];Hemochromatosis/th [Therapy];*Hemochromatosis;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver/pa [Pathology];Liver Failure/di [Diagnosis];Liver Failure/et [Etiology];Liver Failure/pp [Physiopathology];Liver Failure/th [Therapy];*Liver Failure;Liver Transplantation;Penicillamine/tu [Therapeutic Use];*Phlebotomy/mt [Methods];Prognosis;Trientine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Kanwar, P.;Kowdley, K. V.",2014,Jan,https://dx.doi.org/10.1016/j.mcna.2013.09.008,0,0,
140,Assessment of trace elements in human brain using inductively coupled plasma mass spectrometry,"Recent brain research reveals a major role of trace elements in various diseases such as multiple sclerosis, Alzheimer's and Wilson's disease. The majority of published tissue concentrations dates back decades, and was assessed with various methods. Little is known about hemispherical differences, the correlation of trace elements or age-dependent changes in the human brain. Thus, the aim of this study was to examine trace element concentrations in different human brain regions after whole brain formalin fixation. 549 samples of 13 brain regions were investigated in 11 deceased subjects without known history of brain pathology. Regional wet-to-dry mass ratios and concentrations of iron, copper, magnesium, manganese, calcium and zinc were determined using inductively coupled plasma mass spectrometry. Cortical gray matter revealed higher water content (wet-to-dry mass ratios 5.84-6.40) than white matter regions (wet-to-dry mass ratios 2.95-3.05). Element concentrations displayed specific regional differences. Good linear correlation of concentrations between elements was found for iron/copper as well as for manganese/magnesium (Spearman's rank correlation coefficient 0.74 and 0.65, respectively). Significant inter-hemispherical differences were found for copper in occipital white matter, for magnesium and calcium in putamen and for iron and copper in temporal white matter. An age dependent increase was seen in cortical gray matter for calcium, for magnesium in all regions except in cortical gray matter, for copper in substantia nigra and for zinc in occipital cortex. The presented trace element concentrations can serve as a fundamental basis for further brain research. Wet-to-dry mass ratios allow a comparison with reference data from other studies. Copyright © 2013 Elsevier GmbH. All rights reserved.","Aged;Aged, 80 and over;*Brain/me [Metabolism];Female;Humans;Male;*Mass Spectrometry/mt [Methods];Middle Aged;Reproducibility of Results;*Trace Elements/an [Analysis];0 (Trace Elements)","Krebs, N.;Langkammer, C.;Goessler, W.;Ropele, S.;Fazekas, F.;Yen, K.;Scheurer, E.",2014,Jan,https://dx.doi.org/10.1016/j.jtemb.2013.09.006,0,0,
141,Potent and long-lasting inhibition of human P2X2 receptors by copper,"P2X receptors are ion channels gated by ATP. In rodents these channels are modulated by zinc and copper. Zinc is co-released with neurotransmitter at some synapses and can modulate neuronal activity, but the role of copper in the brain is unclear. Rat P2X2 receptors show potentiation by 2-100 muM zinc or copper in the presence of a submaximal concentration of ATP but are inhibited by zinc or copper at concentrations above 100 muM. In contrast, human P2X2 (hP2X2) receptors show no potentiation and are strongly inhibited by zinc over the range of 2-100 muM. The effect of copper on hP2X2 is of interest because there are human brain disorders in which copper concentration is altered. We found that hP2X2 receptors are potently inhibited by copper (IC50 = 40 nM). ATP responsiveness recovered extremely slowly after copper washout, with full recovery requiring over 1 h. ATP binding facilitated copper binding but not unbinding from this inhibitory site. A mutant receptor in which the first six extracellular cysteines were deleted, C(1-6)S, showed normal copper inhibition, however reducing agents dramatically accelerated recovery from copper inhibition in wild type hP2X2 and the C(1-6)S mutant, indicating that the final two disulfide bonds are required to maintain the high affinity copper binding site. Three histidine residues required for normal zinc inhibition were also required for normal copper inhibition. Humans with untreated Wilson's disease have excess amounts of copper in the brain. The high copper sensitivity of hP2X2 receptors suggests that they are non-functional in these patients. Copyright © 2013 Elsevier Ltd. All rights reserved.","Animals;*Copper/pd [Pharmacology];Humans;*Purinergic P2X Receptor Antagonists/pd [Pharmacology];Rats;*Receptors, Purinergic P2X2/me [Metabolism];Species Specificity;Xenopus laevis;0 (Purinergic P2X Receptor Antagonists);0 (Receptors, Purinergic P2X2);789U1901C5 (Copper)","Punthambaker, S.;Hume, R. I.",2014,Feb,https://dx.doi.org/10.1016/j.neuropharm.2013.09.001,0,0,
142,Therapeutic plasma exchange as de-coppering technique in intensive care for an adult in a Wilson's crisis,,Chelating Agents/tu [Therapeutic Use];*Copper/bl [Blood];*Critical Care/mt [Methods];Critical Illness;Fatal Outcome;Female;*Hemodiafiltration/mt [Methods];*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/th [Therapy];Humans;Middle Aged;Penicillamine/tu [Therapeutic Use];*Plasma Exchange/mt [Methods];Renal Insufficiency/bl [Blood];Renal Insufficiency/et [Etiology];*Renal Insufficiency/th [Therapy];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Reynolds, H. V.;Talekar, C. R.;Bellapart, J. B.;Leggett, B. A.;Boots, R. J.",2013,Nov,,0,0,
143,Acute focal dystonia induced by a tricyclic antidepressant in a patient with Wilson disease: a case report,"The authors present the case of a 19-year-old patient with Wilson disease (WD) who developed symptoms of acute focal dystonia of the left hand (a 'starfish' hand presentation) shortly after treatment with the tricyclic antidepressant clomipramine. The diagnosis of WD was made 8 months earlier based on abnormal copper metabolism parameters and was confirmed by genetic testing. Initially, the patient presented with akathisia, sialorrhea, oromandibular dystonia (occasionally grimacing) and slight dysarthria. The patient's symptoms diminished after treatment with d-penicillamine was initiated. No further deterioration was observed after copper-chelating therapy was started. The authors diagnosed acute focal dystonia induced by clomipramine. Botulinum toxin and intensive rehabilitation was initiated; complete regression of hand dystonia was observed. Based on the case, the authors suggest that care should be exercised with regard to starting medications that could potentially impact the extrapyramidal system in WD patients.","*Antidepressive Agents, Tricyclic/ae [Adverse Effects];Antidotes/tu [Therapeutic Use];Botulinum Toxins/tu [Therapeutic Use];*Chelating Agents/tu [Therapeutic Use];*Clomipramine/ae [Adverse Effects];Copper/tu [Therapeutic Use];*Dystonia/ci [Chemically Induced];Hand;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Neurologic Examination/mt [Methods];*Penicillamine/tu [Therapeutic Use];Remission Induction;Treatment Outcome;Young Adult;0 (Antidepressive Agents, Tricyclic);0 (Antidotes);0 (Chelating Agents);789U1901C5 (Copper);EC 3-4-24-69 (Botulinum Toxins);GNN1DV99GX (Penicillamine);NUV44L116D (Clomipramine)","Litwin, T.;Chabik, G.;Czlonkowska, A.",2013,Sep-Oct,,0,0,
144,"Extensive striatal, cortical, and white matter brain MRI abnormalities in Wilson disease",,Adolescent;*Cerebral Cortex/pa [Pathology];*Cerebrum/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Chelation Therapy/mt [Methods];*Corpus Striatum/pa [Pathology];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;*Leukoencephalopathies/pa [Pathology];*Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];Seizures/pa [Pathology];Treatment Outcome;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Trocello, J. M.;Woimant, F.;El Balkhi, S.;Guichard, J. P.;Poupon, J.;Chappuis, P.;Feillet, F.",2013,Oct 22,https://dx.doi.org/10.1212/WNL.0b013e3182a95883,0,0,
145,Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease,"The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.","Administration, Oral;Adolescent;Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Chelation Therapy/ae [Adverse Effects];*Chelation Therapy/mt [Methods];Child;Copper/ur [Urine];Drug Administration Schedule;Drug Hypersensitivity/et [Etiology];Drug Therapy, Combination;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Injections, Intravenous;Male;Neutropenia/ci [Chemically Induced];Partial Thromboplastin Time;Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Prothrombin Time;Thrombocytopenia/ci [Chemically Induced];Time Factors;Treatment Outcome;Unithiol/ad [Administration & Dosage];Unithiol/ae [Adverse Effects];*Unithiol/tu [Therapeutic Use];0 (Chelating Agents);4076-02-2 (Unithiol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Xu, S. Q.;Li, X. F.;Zhu, H. Y.;Liu, Y.;Fang, F.;Chen, L.",2013,Oct,https://dx.doi.org/10.1007/s11596-013-1190-z,0,1,
146,Wilson's disease in pregnancy: case series and review of literature,"BACKGROUND: Wilson's disease is a rare, autosomal recessive inherited disorder characterized by impaired liver metabolism of copper leading to decreased biliary excretion and incorporation of ceruloplasmin levels mainly in the liver and brain. Untreated Wilson's disease has been shown to cause subfertility and even in cases where pregnancy occurs, it often results in spontaneous miscarriage. CASE PRESENTATIONS: We present four cases of successful pregnancy outcomes in three patients diagnosed with Wilson's disease along with the literature review. All the patients were managed with zinc sulphate without any postnatal complications. CONCLUSION: Patients with Wilson's disease receiving regular treatment who remain asymptomatic are usually able to conceive and achieve successful outcomes. However, these pregnancies should be considered high risk and merit regular surveillance.","Adult;Asymptomatic Diseases;*Brain/de [Drug Effects];Brain/me [Metabolism];Brain/pa [Pathology];Ceruloplasmin/me [Metabolism];Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;*Infertility, Female/pc [Prevention & Control];*Liver/de [Drug Effects];Liver/me [Metabolism];Liver/pa [Pathology];Pregnancy;Risk Factors;Treatment Outcome;*Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin)","Malik, A.;Khawaja, A.;Sheikh, L.",2013,Oct 18,https://dx.doi.org/10.1186/1756-0500-6-421,0,0,
147,"Wilson's disease, 100 years later","Texts published, in 1912, 100 years ago, by Sir K. Wilson on his eponymous disease in Brain, The Lancet and La Revue Neurologique highlight the relevance of his descriptions in the light of the current knowledge. Wilson's invocation of an ""unknown toxin"" appears today as a prophetic intuition as the presence of excess copper in the liver was mentioned for the first time a year later whereas the role of copper in this disease was not described until 1929. Progress has been made to better understand the physiology of Wilson's disease (WD). The ATP7B gene implicated in WD is located on chromosome 13 and more than 500 mutations and 100 polymorphisms have been to date identified. The phenotypic expression is highly variable, even within a family. This can partly be explained by environmental factors as nutrition. Modulator genes are also involved in the phenotypic expression of the disease. Most of symptoms observed in WD have already been described in detail by Wilson in 1912, but subsequent progress was made over the following 100 years, helping the physician diagnose WD. Hepatic and neurological symptoms are the most frequent expressions of the disease. Other extrahepatic features include renal manifestations, osteoarticular disorders, myocardial abnormalities, endocrine disturbances, realizing a multisystemic disease. The diagnosis of the disease is based on a combination of clinical symptoms, biological, radiological and genetic data and new tools (Brain MRI, relative exchangeable copper...) allow reducing delay to diagnosis. Therapeutic findings have also changed the disease prognosis. Treatment is based on the use of copper chelators to promote copper excretion from the body (D-penicillamine and Triethylenetetramine) and zinc salts to reduce copper absorption. Tetratiomolybdate appears to be a promising treatment. While significant progress has been made during this century, many physiological aspects of this disease remain unknown and require further research to find answers in the next 100 years. Copyright © 2013 Elsevier Masson SAS. All rights reserved.","Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/hi [History];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;History, 20th Century;Humans;Liver Diseases/et [Etiology];Nervous System Diseases/et [Etiology];0 (Chelating Agents);789U1901C5 (Copper)","Trocello, J. M.;Broussolle, E.;Girardot-Tinant, N.;Pelosse, M.;Lachaux, A.;Lloyd, C.;Woimant, F.",2013,Dec,https://dx.doi.org/10.1016/j.neurol.2013.05.002,0,0,
148,Zinc monotherapy and a low-copper diet are beneficial in patients with Wilson disease after liver transplantation,,Adolescent;Adult;*Copper/ad [Administration & Dosage];Copper/me [Metabolism];*Diet/mt [Methods];Female;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/th [Therapy];Humans;*Liver Transplantation/ae [Adverse Effects];Male;Young Adult;*Zinc/ad [Administration & Dosage];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Ni, W.;Dong, Q. Y.;Zhang, Y.;Wu, Z. Y.",2013,Nov,https://dx.doi.org/10.1111/cns.12167,0,0,
149,Mowat-Wilson syndrome: the first report of an association with central nervous system tumors,"Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and multiple congenital anomalies including Hirschsprung's disease, intellectual disability, and prominent facial features are present. At molecular level, MWS is characterized by many different described mutations in the zinc finger E-box protein 2 (ZEB2) gene, ultimately leading to loss of gene function. This report is the first to describe the association of MWS with two different asynchronous malignant brain tumors (medulloblastoma and glioblastoma) occurring in a child.","*Brain Neoplasms/co [Complications];Brain Neoplasms/pa [Pathology];Cerebellar Neoplasms/co [Complications];Cerebellar Neoplasms/pa [Pathology];Child, Preschool;Facies;*Glioblastoma/co [Complications];Glioblastoma/pa [Pathology];*Hirschsprung Disease/co [Complications];Humans;*Intellectual Disability/co [Complications];Male;*Medulloblastoma/co [Complications];Medulloblastoma/pa [Pathology];*Microcephaly/co [Complications];*Neoplasms, Second Primary/co [Complications];Neoplasms, Second Primary/pa [Pathology];Mowat-Wilson syndrome","Valera, E. T.;Ferraz, S. T.;Brassesco, M. S.;Zhen, X.;Shen, Y.;dos Santos, A. C.;Neder, L.;Oliveira, R. S.;Scrideli, C. A.;Tone, L. G.",2013,Dec,https://dx.doi.org/10.1007/s00381-013-2283-5,0,0,
150,Hepatocellular carcinoma in a young man with resting and postural tremors,"A 25-year-old man who was normally fit and well, presented with a 2-year history of progressively worsening tremor. His tremor was generalised, affecting head, neck and all four limbs. One of the patient's brothers had suffered from similar problems, but never sought medical attention. Examination revealed a generalised tremor, of greater amplitude on the patient's left side, which increased in its amplitude upon exertion. Slit-lamp examination revealed bilateral Kayser-Fleischer rings and serum caeruloplasmin was found to be low, while 24 h urinary copper excretion was elevated. A diagnosis of Wilson's disease was made and an abdominal ultrasound was performed, revealing evidence of portal hypertension and a hyperechoic hepatic nodule, later confirmed to be hepatocellular carcinoma. The patient underwent partial hepatic resection and was started on D-penicillamine.","Adult;*Carcinoma, Hepatocellular/co [Complications];Carcinoma, Hepatocellular/di [Diagnosis];Diagnosis, Differential;Follow-Up Studies;Humans;*Liver Neoplasms/co [Complications];Liver Neoplasms/di [Diagnosis];Male;*Posture;*Rest;Tomography, X-Ray Computed;Tremor/di [Diagnosis];*Tremor/et [Etiology]","Waqar, M.;Vohra, A. H.",2013,Sep 30,https://dx.doi.org/10.1136/bcr-2013-201198,0,0,
151,50 Years Ago in The Journal of Pediatrics: hepatolenticular degeneration: observations on a case treated with D-penicillamine,,"Adenosine Triphosphatases/ge [Genetics];Cation Transport Proteins/ge [Genetics];Chelating Agents/pd [Pharmacology];Copper/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];History, 20th Century;Humans;Mutation;*Pediatrics/hi [History];Penicillamine/tu [Therapeutic Use];0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Choquette, M.",2013,Oct,https://dx.doi.org/10.1016/j.jpeds.2013.04.036,0,0,
152,Alterations of cortical excitability and central motor conduction time in Wilson's disease,"Wilson's disease (WD) leads to widespread structural alterations of central nervous system and our objectives were to determine the cortical excitability changes in WD by using transcranial magnetic stimulation (TMS). Thirteen patients with WD, diagnosed by the presence of Kayser-Fleischer ring and biochemical tests, were studied. TMS was performed using a figure-of-eight coil attached to Magstim 200 stimulator. Motor evoked potentials (MEP) were recorded from right first dorsal interosseous at rest. Resting motor threshold (RMT) was determined using standard techniques and central motor conduction time (CMCT) by 'F' wave method. Comparison was made with control data of our laboratory. Dysarthria was the presenting symptom in 5 patients (38.5%) and chorea, tremors, dystonia and abnormal gait in 2 patients each (15.4%). RMT was recordable in 10 patients and not recordable in 3. Compared to controls, patients in whom RMT was recordable, had significantly higher mean RMT (80.9 +/- 14.8 vs. 41.1 +/- 7, p<0.0001) and CMCT (6.7 +/- 0.5 ms vs. 4.8 +/- 0.6 ms; p<0.0001). In 2 of the 3 patients with non-recordable RMT, MEP could be obtained with active contraction. CMCT in these 2 patients was also prolonged. Patients with WD have reduced cortical excitability and prolonged CMCT which may be due to the intracortical presynaptic motor dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.","Adolescent;Adult;*Cerebral Cortex/pp [Physiopathology];Child;Evoked Potentials, Motor;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];Time Factors;Transcranial Magnetic Stimulation;Young Adult;Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine)","Jhunjhunwala, K.;Prashanth, D. K.;Netravathi, M.;Nagaraju, B. C.;Pal, P. K.",2013,Oct 11,https://dx.doi.org/10.1016/j.neulet.2013.08.023,0,0,
153,Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate,"AIM: To investigate the side effects of a zinc sulphate therapy in a cohort of Polish pediatric patients with Wilson's disease. METHODS: We retrospectively analyzed a cohort of 53 pediatric patients with Wilson's disease treated at the Children's Memorial Health Institute in Warsaw, Poland between the years 1996 and 2011 with zinc sulphate. Patients were diagnosed with Wilson's disease according to the scoring system of Ferenci, with 49 cases confirmed by mutation analysis. Data about the dosage scheme of zinc sulphate, side effects and efficacy and toxicity of the treatment were collected and recorded in the patient's medical chart at each visit to the hospital. RESULTS: Mean age of diagnosis for the entire cohort was 10 years (range, 2.5-17 years). Duration of treatment with zinc sulfate was 83.3 wk (range, 8-344 wk). Side effects, all of gastrointestinal origin, were observed in 21 patients (40%--9 males and 12 females), irrespective of the duration of therapy. Thirteen out of 21 patients were over the age of 10 years. The most common ATP7B mutation was p.H1069Q. Esophagogastroduodenoscopy, performed in 7 patients (33.3%) suffering from persistent and severe abdominal pain, revealed gastrointestinal ulcerations or erosions with negative Helicobacter pylori tests in all subjects investigated. The above mentioned 7 patients were treated with proton pump inhibitors. Three of those experienced resolution of symptoms, whereas proton-pump inhibitors failed to alleviate symptoms of the remaining four children and conversion of therapy to D-penicillamine was needed. CONCLUSION: Zinc sulphate appears to cause significant gastrointestinal side effects, which children on therapy for Wilson's disease should be closely monitored for.","Adenosine Triphosphatases/ge [Genetics];Adolescent;Cation Transport Proteins/ge [Genetics];Child;Child, Preschool;Endoscopy, Digestive System;Female;*Gastrointestinal Diseases/ci [Chemically Induced];Gastrointestinal Tract/de [Drug Effects];*Gastrointestinal Tract/pa [Pathology];Helicobacter Infections;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Mutation;Penicillamine/tu [Therapeutic Use];Poland;Retrospective Studies;*Ulcer/ci [Chemically Induced];*Zinc Sulfate/ae [Adverse Effects];0 (Cation Transport Proteins);7733-02-0 (Zinc Sulfate);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Wiernicka, A.;Janczyk, W.;Dadalski, M.;Avsar, Y.;Schmidt, H.;Socha, P.",2013,Jul 21,https://dx.doi.org/10.3748/wjg.v19.i27.4356,0,1,
154,A viewpoint about the treatment of Wilson's disease.[Retraction in Can J Neurol Sci. 2013 Nov;40(6):A5; PMID: 24280413],,Adult;Child;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc),"Rana, A. Q.;Avan, A.;Aftab, I.;Monsoor, W.;Hoogenraad, T. U.",2013,Jul,,0,0,
155,"The treatment of Wilson's disease, a rare genetic disorder of copper metabolism","Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.","Brain/de [Drug Effects];Brain/me [Metabolism];Brain/pp [Physiopathology];Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];Cornea/de [Drug Effects];Cornea/me [Metabolism];Cornea/pp [Physiopathology];Dimercaprol/pd [Pharmacology];*Dimercaprol/tu [Therapeutic Use];Drug Discovery/hi [History];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];History, 20th Century;Humans;Liver/de [Drug Effects];Liver/me [Metabolism];Liver/pp [Physiopathology];Molybdenum/pd [Pharmacology];*Molybdenum/tu [Therapeutic Use];Penicillamine/pd [Pharmacology];*Penicillamine/tu [Therapeutic Use];Rare Diseases/dt [Drug Therapy];Rare Diseases/ge [Genetics];Rare Diseases/me [Metabolism];Rare Diseases/pp [Physiopathology];Trientine/pd [Pharmacology];*Trientine/tu [Therapeutic Use];Zinc Sulfate/pd [Pharmacology];*Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);0CPP32S55X (Dimercaprol);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Purchase, R.",2013,,,0,0,
156,Recovery after copper-deficiency myeloneuropathy in Wilson's disease,,Adult;*Copper/df [Deficiency];Copper/me [Metabolism];*Deficiency Diseases/ci [Chemically Induced];Deficiency Diseases/me [Metabolism];Deficiency Diseases/pa [Pathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Male;*Nervous System Diseases/ci [Chemically Induced];Nervous System Diseases/me [Metabolism];Nervous System Diseases/pa [Pathology];Spinal Cord/pa [Pathology];*Spinal Cord Diseases/ci [Chemically Induced];Spinal Cord Diseases/me [Metabolism];Spinal Cord Diseases/pa [Pathology];Trientine/ae [Adverse Effects];Trientine/tu [Therapeutic Use];Zinc Sulfate/ae [Adverse Effects];Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);SJ76Y07H5F (Trientine),"Teodoro, T.;Neutel, D.;Lobo, P.;Geraldo, A. F.;Conceicao, I.;Rosa, M. M.;Albuquerque, L.;Ferreira, J. J.",2013,Jul,https://dx.doi.org/10.1007/s00415-013-6963-6,0,0,
157,Coincidence of 2 severe chronic diseases: presymptomatic diagnosis of Wilson disease in a boy with severe haemophilia A,,Adenosine Triphosphatases/ge [Genetics];Cation Transport Proteins/ge [Genetics];Chromosome Deletion;Chromosome Inversion;DNA Mutational Analysis;Early Diagnosis;Factor VIII/ge [Genetics];Factor VIII/tu [Therapeutic Use];*Hemophilia A/co [Complications];*Hemophilia A/di [Diagnosis];Hemophilia A/ge [Genetics];Hemophilia A/th [Therapy];*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Heterozygote Detection;Humans;Introns;Liver Function Tests;Male;Penicillamine/tu [Therapeutic Use];Ultrasonography;Vitamin B 6/tu [Therapeutic Use];0 (Cation Transport Proteins);8059-24-3 (Vitamin B 6);9001-27-8 (Factor VIII);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine),"Hainmann, I.;Woltering, T.;Greiner, P.;Nakamura, L.;Podskarbi, T.;Oldenburg, J.;Zieger, B.",2013,May,https://dx.doi.org/10.1055/s-0033-1343482,0,0,
158,Re-evaluation of the indications for liver transplantation in Wilson's disease based on the outcomes of patients referred to a transplant center,"The aim of this study was to re-evaluate the indications and timing of LT for WD. From 2000 to 2009, eight patients with WD who had been referred to our institution for LT were enrolled in this study. The mean patient age was 15.9 yr (range, 7-37 yr). Four patients could not receive LT, because there were no available donors. All four patients were treated with chelating agent medication. Three of them (two of two patients with fulminant WD and one of two with cirrhotic WD) who did not undergo LT are still alive and doing well with stable liver functional tests. Only one of the patients with cirrhotic WD who did not undergo LT died of hepatic failure. Even among the four patients who underwent LT, one with fulminant WD recovered from hepatic encephalopathy with apheresis therapy and chelating agent. He later required LT because of severe neutropenia from d-penicillamine. The other three patients who underwent LT recovered and have been doing well. Some of the patients with WD can recover and avoid LT with medical treatment. Even when WD has progressed liver cirrhosis and/or fulminant hepatic failure at the time of diagnosis, medical treatment should be tried before considering LT. Copyright © 2013 John Wiley & Sons A/S.","Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Child;Female;Follow-Up Studies;Hepatic Encephalopathy/et [Etiology];Hepatic Encephalopathy/th [Therapy];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Failure, Acute/th [Therapy];Liver Function Tests;*Liver Transplantation/mt [Methods];Liver Transplantation/st [Standards];Male;Referral and Consultation;Treatment Outcome;Young Adult;0 (Chelating Agents)","Ohya, Y.;Okajima, H.;Honda, M.;Hayashida, S.;Suda, H.;Matsumoto, S.;Lee, K. J.;Yamamoto, H.;Takeichi, T.;Mitsubuchi, H.;Asonuma, K.;Endo, F.;Inomata, Y.",2013,Jun,https://dx.doi.org/10.1111/petr.12085,0,0,
159,Update on zinc deficiency and excess in clinical pediatric practice,"The critical importance of adequate zinc status to human health, including normal growth and development, is indisputable. The high prevalence of zinc deficiency on a global basis and its importance to public health have been well documented through large-scale randomized controlled zinc supplementation trials. Similar evidence in the clinical setting, however, is much less widely available due to the nonspecific features of zinc deficiency and to the lack of sensitive biomarkers to detect zinc deficiency, especially that of a mild degree of severity. The current understanding of zinc homeostasis indicates that the primary determinants of zinc absorption are the amount of zinc ingested and dietary phytate, the latter having a major effect on zinc bioavailability. In normal as well as in many pathologic conditions, the gastrointestinal tract is the major site of zinc losses resulting from secretion of endogenous zinc into the lumen and subsequent excretion in the feces. The amount excreted is dependent on host status, the amount reabsorbed, and sometimes the presence of pathophysiologic conditions, including diarrhea and steatorrhea. Assessment in the clinical setting dictates that the clinician obtain a careful medical and diet history, recognize clinical presentations in which zinc adequacy may be compromised, and link this risk with nonspecific but plausible manifestations of deficiency. Examples discussed in this article include primary zinc deficiency due to dietary inadequacy (older breastfed infants or toddlers without zinc-rich complementary foods); genetically based deficiency (acrodermatitis enteropathica, acquired zinc deficiency of lactogenic origin), and acquired secondary deficiency in low birth weight and prematurity, gastrointestinal and hepatic disease, and cystic fibrosis. Evidence for efficacy of zinc therapy with pharmacologic doses for two conditions, Wilson's disease and viral upper respiratory infections, is also discussed. Copyright © 2013 S. Karger AG, Basel.","Acrodermatitis/dt [Drug Therapy];Acrodermatitis/ge [Genetics];Biomarkers/bl [Blood];*Child Nutritional Physiological Phenomena;Child, Preschool;Diarrhea;Diet;*Dietary Supplements;Homeostasis;Humans;Infant;Liver Diseases;Mutation;Pediatrics;Randomized Controlled Trials as Topic;*Zinc/ad [Administration & Dosage];Zinc/bl [Blood];*Zinc/df [Deficiency];0 (Biomarkers);J41CSQ7QDS (Zinc);Acrodermatitis enteropathica","Krebs, N. F.",2013,,https://dx.doi.org/10.1159/000348261,0,0,
160,Inborn errors of copper metabolism,"Two copper-transporting ATPases are essential for mammalian copper homeostasis: ATP7A, which mediates copper uptake in the gastrointestinal tract and copper delivery to the brain, and ATP7B, which mediates copper excretion by the liver into bile. Mutations in ATP7A may cause three distinct X-linked conditions in infants, children, or adolescents: Menkes disease, occipital horn syndrome (OHS), and a newly identified allelic variant restricted to motor neurons called X-linked distal hereditary motor neuropathy. These three disorders show variable neurological findings and ages of onset. Menkes disease presents in the first several months of life with failure to thrive, developmental delay, and seizures. OHS features more subtle developmental delays, dysautonomia, and connective tissue abnormalities beginning in early childhood. ATP7A-related distal motor neuropathy presents even later, often not until adolescence or early adulthood, and involves a neurological phenotype that resembles Charcot-Marie-Tooth disease, type 2. These disorders may be treatable through copper replacement or ATP7A gene therapy. In contrast, mutations in ATP7B cause a single known phenotype, Wilson disease, an autosomal recessive trait that results from copper overload rather than deficiency. Dysarthria, dystonia, tremor, gait abnormalities, and psychiatric problems may be presenting symptoms, at ages from 10 to 40 years. Excellent treatment options exist for Wilson disease, based on copper chelation. In the past 2 years (2012-2013), three new autosomal recessive copper metabolism conditions have been recognized: 1) Huppke-Brendel syndrome caused by mutations in an acetyl CoA transporter needed for acetylation of one or more copper proteins, 2) CCS deficiency caused by mutations in the copper chaperone to SODI, and 3) MEDNIK syndrome, which revealed that mutations in the sigma1A subunit of adaptor protein complex 1 (AP-1) have detrimental effects on trafficking of ATP7A and ATP7B. Copyright © 2013 Elsevier B.V. All rights reserved.",Chelating Agents/tu [Therapeutic Use];Child;*Copper/me [Metabolism];*Cutis Laxa/di [Diagnosis];Cutis Laxa/ge [Genetics];Cutis Laxa/me [Metabolism];*Ehlers-Danlos Syndrome/di [Diagnosis];Ehlers-Danlos Syndrome/ge [Genetics];Ehlers-Danlos Syndrome/me [Metabolism];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Infant;*Menkes Kinky Hair Syndrome/di [Diagnosis];Menkes Kinky Hair Syndrome/ge [Genetics];Menkes Kinky Hair Syndrome/me [Metabolism];Penicillamine/tu [Therapeutic Use];Prognosis;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);Occipital horn syndrome,"Kaler, S. G.",2013,,https://dx.doi.org/10.1016/B978-0-444-59565-2.00045-9,0,0,
161,Penicillamine revisited: historic overview and review of the clinical uses and cutaneous adverse effects,"Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.",*Chelating Agents/ae [Adverse Effects];Humans;*Penicillamine/ae [Adverse Effects];*Skin Diseases/ci [Chemically Induced];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Ishak, R.;Abbas, O.",2013,Jun,https://dx.doi.org/10.1007/s40257-013-0022-z,0,0,
162,Hepatocellular carcinoma in a non-cirrhotic patient with Wilson's disease,"We report the exceptional case of hepatocellular carcinoma in a non-cirrhotic patient, whose Wilson's disease was diagnosed at the unusual age of 58 years. The liver histology revealed macrovesicular steatosis with fibrosis, but no cirrhosis. The disease was treated with D-penicillamine for 3 years until acute discomfort in the right upper quadrant led to detection of multifocal hepatocellular carcinoma, which was successfully resected. The histological examination confirmed the malignant nature of the 4 lesions, which were classified according to Edmondson and Steiner as poorly differentiated hepatocellular carcinoma grade 3. The non-tumoral parenchyma showed 80% steatosis with ballooned cells, lobular inflammation, septal fibrosis but no cirrhosis. Hepatocellular carcinoma is rare in Wilson's disease, especially in the absence of cirrhosis. The literature's 28 published cases are reviewed and the contributory role of copper in the hepatocarcinogenic process is discussed.","Biopsy;Carcinoma, Hepatocellular/co [Complications];*Carcinoma, Hepatocellular/di [Diagnosis];Copper/me [Metabolism];Exons;Fibrosis/di [Diagnosis];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Humans;Inflammation;Liver Neoplasms/co [Complications];*Liver Neoplasms/di [Diagnosis];Male;Middle Aged;Mutation, Missense;Tomography, X-Ray Computed;Treatment Outcome;789U1901C5 (Copper)","Thattil, R.;Dufour, J. F.",2013,Apr 07,https://dx.doi.org/10.3748/wjg.v19.i13.2110,0,0,
163,Brain metal accumulation in Wilson's disease,"INTRODUCTION: Brain metal accumulation is suggested in the pathogenesis of numerous neurodegenerative disorders. In Wilson's disease (WD), only copper has been examined. The aim of the present study was to evaluate the copper, iron, manganese, and zinc concentrations in autopsy tissue samples from the brains of WD patients. METHODS: The study material consisted of 17 brains (12 WD patients, 5 controls) obtained at autopsy. Samples were taken from four different regions of each brain: frontal cortex, putamen, pons, and nucleus dentatus. The copper, manganese, and zinc content were determined using inductively coupled plasma mass spectrometry, and iron was assessed using flame atomic absorption spectroscopy. The results were analyzed according to select clinical variables. RESULTS: Copper content was increased homogenously in all investigated structures of the WD brains compared to controls (41.0 +/- 18.6 mug/g vs.5.4 +/- 1.8 mug/g; P<0.01). The mean concentrations of iron, manganese, and zinc were similar in WD and controls, but the iron level in the nucleus dentatus was higher in WD compared to controls (56.8 +/- 14.1 mug/g vs. 32.6 +/- 6.0 mug/g; P<0.05). Gender, age, and type and duration of WD treatment did not impact brain metals storage, but some correlations between the duration of the disease and copper and iron accumulation were observed. CONCLUSIONS: During the course of WD, copper accumulates equally in different parts of the brain. Zinc and manganese do not seem to be involved in WD pathology, but increased levels of iron were found in the nucleus dentatus. Thus, additional studies of brain iron accumulation in WD are needed. Copyright © 2013 Elsevier B.V. All rights reserved.","Adult;Analysis of Variance;Autopsy;*Brain/me [Metabolism];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Metals/bl [Blood];*Metals/me [Metabolism];Retrospective Studies;Statistics, Nonparametric;Young Adult;0 (Metals)","Litwin, T.;Gromadzka, G.;Szpak, G. M.;Jablonka-Salach, K.;Bulska, E.;Czlonkowska, A.",2013,Jun 15,https://dx.doi.org/10.1016/j.jns.2013.03.021,0,0,
164,Obliterating bronchiolitis in a patient treated with (D)-penicillamine,,"*Bronchiolitis Obliterans/ci [Chemically Induced];Bronchiolitis Obliterans/dg [Diagnostic Imaging];Bronchiolitis Obliterans/dt [Drug Therapy];Bronchiolitis Obliterans/pa [Pathology];Bronchiolitis Obliterans/su [Surgery];Bronchodilator Agents/tu [Therapeutic Use];*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Chelation Therapy/ae [Adverse Effects];Combined Modality Therapy;Copper;Dyslipidemias/co [Complications];Dyslipidemias/dt [Drug Therapy];Graves Disease/co [Complications];Graves Disease/rt [Radiotherapy];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Hypertension/co [Complications];Hypertension/dt [Drug Therapy];Lung Transplantation;Male;Methylprednisolone/tu [Therapeutic Use];Middle Aged;Oxygen Inhalation Therapy;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Respiratory Insufficiency/et [Etiology];Respiratory Insufficiency/th [Therapy];Tomography, X-Ray Computed;0 (Bronchodilator Agents);0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);X4W7ZR7023 (Methylprednisolone)","Bruguera-Avila, N.;Sanchez-Martinez, E.;Garcia-Olive, I.;Perez-Ochoa, J. F.;Martinez-Barenys, C.;Ruiz-Manzano, J.",2013,Sep,https://dx.doi.org/10.1016/j.arbres.2013.02.002,0,0,
165,Trientine reduces BACE1 activity and mitigates amyloidosis via the AGE/RAGE/NF-kappaB pathway in a transgenic mouse model of Alzheimer's disease,"AIMS: There is mounting evidence that the transition metal copper may play an important role in the pathophysiology of Alzheimer's disease (AD). Triethylene tetramine dihydrochloride (trientine), a CuII-selective chelator, is a commonly used treatment for Wilson's disease to decrease accumulated copper, and thereby decreases oxidative stress. In the present study, we evaluated the effects of a 3-month treatment course of trientine (Trien) on amyloidosis in 7-month-old beta-amyloid (Abeta) precursor protein and presenilin-1 (APP/PS1) double transgenic (Tg) AD model mice. RESULTS: We observed that Trien reduced the level of advanced glycation end products (AGEs), and decreased Abeta deposition and synapse loss in brain of APP/PS1 mice. Importantly, we found that Trien blocked the receptor for AGEs (RAGE), downregulated beta-site APP cleaving enzyme 1 (BACE1), inhibited amyloidogenic APP cleavage, and subsequently reduced Abeta levels. In vitro, in SH-SY5Y cells overexpressing Swedish mutant APP, Trien-mediated downregulation of BACE1 occurred via inhibition of the NF-kappaB signaling pathway. INNOVATION: In this study, we demonstrated for the first time that Trien inhibited amyloidogenic pathway including targeting the downregulation of RAGE and NF-kappaB. CONCLUSION: Trien might mitigate amyloidosis in AD by inhibiting the RAGE/NF-kappaB/BACE1 pathway. Our study demonstrates that Trien may be a viable therapeutic strategy for the intervention and treatment of AD and other AD-like pathologies.","Advanced Glycosylation End Product-Specific Receptor;Alzheimer Disease/bl [Blood];Alzheimer Disease/dt [Drug Therapy];Alzheimer Disease/en [Enzymology];*Amyloid Precursor Protein Secretases/me [Metabolism];*Amyloidosis/en [Enzymology];Amyloidosis/pc [Prevention & Control];Animals;*Aspartic Acid Endopeptidases/me [Metabolism];Cell Line, Tumor;Cerebral Cortex/de [Drug Effects];Cerebral Cortex/me [Metabolism];Ceruloplasmin/me [Metabolism];*Chelating Agents/pd [Pharmacology];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Down-Regulation;Female;Glycosylation End Products, Advanced/me [Metabolism];Humans;Malondialdehyde/me [Metabolism];Mice;Mice, Inbred C57BL;Mice, Transgenic;NF-kappa B/me [Metabolism];Receptors, Immunologic/me [Metabolism];Signal Transduction;Superoxide Dismutase/me [Metabolism];Superoxide Dismutase-1;*Trientine/pd [Pharmacology];Trientine/tu [Therapeutic Use];0 (Advanced Glycosylation End Product-Specific Receptor);0 (Chelating Agents);0 (Glycosylation End Products, Advanced);0 (NF-kappa B);0 (Receptors, Immunologic);0 (SOD1 protein, human);4Y8F71G49Q (Malondialdehyde);789U1901C5 (Copper);EC 1-15-1-1 (Sod1 protein, mouse);EC 1-15-1-1 (Superoxide Dismutase);EC 1-15-1-1 (Superoxide Dismutase-1);EC 1-16-3-1 (Ceruloplasmin);EC 3-4 (Amyloid Precursor Protein Secretases);EC 3-4-23 (Aspartic Acid Endopeptidases);EC 3-4-23-46 (Bace1 protein, mouse);SJ76Y07H5F (Trientine)","Wang, C. Y.;Xie, J. W.;Xu, Y.;Wang, T.;Cai, J. H.;Wang, X.;Zhao, B. L.;An, L.;Wang, Z. Y.",2013,Dec 10,https://dx.doi.org/10.1089/ars.2012.5158,0,0,
166,Discovery of human zinc deficiency: its impact on human health and disease,"The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc-deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.",Cognition Disorders/et [Etiology];*Deficiency Diseases/co [Complications];Deficiency Diseases/me [Metabolism];Growth Disorders/et [Etiology];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Immune System;Macular Degeneration/dt [Drug Therapy];*Nutritional Requirements;*Trace Elements/df [Deficiency];Trace Elements/me [Metabolism];Trace Elements/tu [Therapeutic Use];*Zinc/df [Deficiency];Zinc/me [Metabolism];Zinc/tu [Therapeutic Use];0 (Trace Elements);J41CSQ7QDS (Zinc),"Prasad, A. S.",2013,Mar 01,https://dx.doi.org/10.3945/an.112.003210,0,0,
167,[Wilson's disease: programed wandering?],,"Adenosine Triphosphatases/bl [Blood];Administration, Oral;Adult;Biomarkers;*Carcinoma, Hepatocellular/di [Diagnosis];*Carcinoma, Hepatocellular/et [Etiology];Carcinoma, Hepatocellular/th [Therapy];Cation Transport Proteins/bl [Blood];Ceruloplasmin/me [Metabolism];Chelating Agents/ad [Administration & Dosage];Copper/bl [Blood];Drug Therapy, Combination;Hepatectomy;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;*Liver Neoplasms/di [Diagnosis];*Liver Neoplasms/et [Etiology];Liver Neoplasms/th [Therapy];Male;Penicillamine/ad [Administration & Dosage];Prognosis;Treatment Outcome;Vitamin B 6/ad [Administration & Dosage];Vitamin B Complex/ad [Administration & Dosage];0 (Biomarkers);0 (Cation Transport Proteins);0 (Chelating Agents);12001-76-2 (Vitamin B Complex);789U1901C5 (Copper);8059-24-3 (Vitamin B 6);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Bersier, M.;Pache, I.",2013,Feb 13,,0,0,
168,ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome,"Mowat-Wilson syndrome (MWS) is a severe intellectual disability (ID)-distinctive facial gestalt-multiple congenital anomaly syndrome, commonly associating microcephaly, epilepsy, corpus callosum agenesis, conotruncal heart defects, urogenital malformations and Hirschsprung disease (HSCR). MWS is caused by de novo heterozygous mutations in the ZEB2 gene. The majority of mutations lead to haplo-insufficiency through premature stop codons or large gene deletions. Only three missense mutations have been reported so far; none of which resides in a known functional domain of ZEB2. In this study, we report and analyze the functional consequences of three novel missense mutations, p.Tyr1055Cys, p.Ser1071Pro and p.His1045Arg, identified in the highly conserved C-zinc-finger (C-ZF) domain of ZEB2. Patients' phenotype included the facial gestalt of MWS and moderate ID, but no microcephaly, heart defects or HSCR. In vitro studies showed that all the three mutations prevented binding and repression of the E-cadherin promoter, a characterized ZEB2 target gene. Taking advantage of the zebrafish morphant technology, we performed rescue experiments using wild-type (WT) and mutant human ZEB2 mRNAs. Variable, mutation-dependent, embryo rescue, correlating with the severity of patients' phenotype, was observed. Our data provide evidence that these missense mutations cause a partial loss of function of ZEB2, suggesting that its role is not restricted to repression of E-cadherin. Functional domains other than C-ZF may play a role in early embryonic development. Finally, these findings broaden the clinical spectrum of ZEB2 mutations, indicating that MWS ought to be considered in patients with lesser degrees of ID and a suggestive facial gestalt, even in the absence of congenital malformation.","*Alleles;Amino Acid Sequence;Animals;Cell Line;DNA/me [Metabolism];Disease Models, Animal;Facies;Female;Gene Order;*Hirschsprung Disease/ge [Genetics];Homeodomain Proteins/ch [Chemistry];*Homeodomain Proteins/ge [Genetics];Homeodomain Proteins/me [Metabolism];Humans;*Intellectual Disability/ge [Genetics];Male;*Microcephaly/ge [Genetics];Molecular Sequence Data;*Mutation, Missense;Phenotype;Protein Binding;Repressor Proteins/ch [Chemistry];*Repressor Proteins/ge [Genetics];Repressor Proteins/me [Metabolism];Transcription, Genetic;Zebrafish;Zinc Fingers/ge [Genetics];0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human);9007-49-2 (dna);Mowat-Wilson syndrome","Ghoumid, J.;Drevillon, L.;Alavi-Naini, S. M.;Bondurand, N.;Rio, M.;Briand-Suleau, A.;Nasser, M.;Goodwin, L.;Raymond, P.;Yanicostas, C.;Goossens, M.;Lyonnet, S.;Mowat, D.;Amiel, J.;Soussi-Yanicostas, N.;Giurgea, I.",2013,Jul 01,https://dx.doi.org/10.1093/hmg/ddt114,0,0,
169,The effect of zinc and the role of p53 in copper-induced cellular stress responses,"Metals can directly or indirectly cause an increase in reactive oxygen species (ROS) accumulation in cells, and this may result in programmed cell death. A number of previous studies have shown that zinc (Zn) modulates mitogenic activity via several signalling pathways, such as AKT, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF -kappaB), AP-1 and p53. The exact role that Zn plays in the regulation of apoptosis remains ambiguous. Intracellular free Zn modulates p53 activity and stability, and excess Zn alters the p53 protein structure and down-regulates p53's binding to DNA. Copper (Cu) accumulation causes apoptosis that seems to be mediated by DNA damage and subsequent p53 activation. Cu can also displace Zn from its normal binding site on p53, resulting in abnormal protein folding and disruption of p53 function. In spite of the induction of the tumour suppressor p53, hepatic Cu accumulation significantly increases the risk of cancerous neoplasm both in humans and rats, suggesting that p53 function may be impaired in these cells. It is generally understood that imbalances in Cu and Zn levels may lead to a higher prevalence of p53 mutations. An increased number of p53 mutations have been found in liver samples from Wilson's disease (WD) patients. High levels of the p53 mutation most probably contribute to the pathogenesis of cancer in individuals with WD, but the cause and effect are not clear. The protein p53 also plays a crucial role in the transcriptional regulation of metallothionein, which indicates a novel regulatory role for p53. This review discusses the central role of p53 and the redox-inert metal Zn in the cellular stress responses induced by the redox active biometal Cu. Copyright © 2013 John Wiley & Sons, Ltd.","Animals;Copper/me [Metabolism];*Copper/to [Toxicity];Genes, p53;Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Metallothionein/me [Metabolism];*Oxidative Stress/de [Drug Effects];Radiotherapy;Tumor Suppressor Protein p53/ge [Genetics];*Tumor Suppressor Protein p53/ph [Physiology];Zinc/me [Metabolism];*Zinc/pd [Pharmacology];0 (Tumor Suppressor Protein p53);789U1901C5 (Copper);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc)","Formigari, A.;Gregianin, E.;Irato, P.",2013,Jul,https://dx.doi.org/10.1002/jat.2854,0,0,
170,Trientine-induced neurological deterioration in a patient with Wilson's disease,"Trientine (triethylenetetramine dihydrochloride) is a copper-chelating agent used to treat patients with Wilson's disease (WD). It has been considered safe, rarely causing neurological deterioration during initial treatment. We describe a patient diagnosed with WD who became neurologically disabled after treatment with trientine. On a fluid attenuated inversion recovery sequence, brain MRI showed increased areas of high signal intensity compared with initial brain MRI. The patient's neurological signs partially resolved after cessation of trientine treatment. Our findings suggest that treatment with trientine is associated with a risk of neurological deterioration in patients with WD. Copyright © 2012 Elsevier Ltd. All rights reserved.","Brain/pa [Pathology];*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Dystonia/et [Etiology];Gait Disorders, Neurologic/et [Etiology];Gait Disorders, Neurologic/pa [Pathology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Male;*Nervous System Diseases/ci [Chemically Induced];Nervous System Diseases/co [Complications];Nervous System Diseases/pa [Pathology];*Trientine/ae [Adverse Effects];Trientine/tu [Therapeutic Use];Young Adult;Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Kim, B.;Chung, S. J.;Shin, H. W.",2013,Apr,https://dx.doi.org/10.1016/j.jocn.2012.02.041,0,0,
171,Complex formation equilibria of Cu(II) and Zn(II) with triethylenetetramine and its mono- and di-acetyl metabolites,"Triethylenetetramine (TETA) dihydrochloride, or trientine, is a therapeutic molecule that has long been used as a copper-chelating agent for the second-line treatment of patients with Wilson's disease. More recently, it has also been employed as an experimental therapeutic molecule in diabetes where it improves cardiac structure in patients with diabetic cardiomyopathy and left-ventricular hypertrophy. TETA is metabolized by acetylation, which leads to the formation of two main metabolites in humans and other mammals, monoacetyl-TETA (MAT) and diacetyl-TETA (DAT). These metabolites have been identified in the plasma and urine of healthy and diabetic subjects treated with TETA, and could themselves play a role in TETA-mediated copper chelation and restoration of physiological copper regulation in diabetes. In this regard, a potentiometric and spectrophotometric study of Cu(II)-complex formation equilibria of TETA, MAT and DAT is presented here, to provide a comprehensive evaluation of the stoichiometries of the complexes formed and of their relative stability constants. A potentiometric study has also been conducted on the corresponding Zn(II) complexes, to evaluate any possible interference with TETA-mediated Cu(II) binding by this second physiological transition-metal ion, which is present in similar concentrations in human plasma and which also binds to TETA. An ESI-MS study of these systems has both confirmed the complex formation mechanisms established from the potentiometric and spectrophotometric results, and in addition provided direct information on the stoichiometry of the complexes formed in solution. These data when taken together show that the 1 : 1 complexes formed with Cu(II) and Zn(II) have different degrees of protonation. The stability of the Cu(II) and Zn(II) complexes with the three ligands, evaluated by the parameters pCu and pZn, decreases with the introduction of the acetyl groups. Nevertheless the stability of Cu(II) complexes with MAT is sufficiently high to enable its participation in copper scavenging from the patient. A speciation study of the behavior of TETA and MAT with Cu(II) in the presence of Zn(II) at peri-physiological plasma concentrations is also presented. While Zn(II) did not hinder copper binding, the possibility is raised that prolonged TETA treatment could possibly alter the homeostatic regulation of this essential metal ion. The lack of reliable literature stability constants concerning the Cu(II) and Zn(II) interaction with the major transport proteins in plasma is also briefly considered.","*Coordination Complexes/ch [Chemistry];*Copper/ch [Chemistry];Humans;Hydrogen-Ion Concentration;Ions/ch [Chemistry];Ligands;Osmolar Concentration;Protons;Spectrometry, Mass, Electrospray Ionization;Spectrophotometry, Ultraviolet;Trientine/ch [Chemistry];*Trientine/me [Metabolism];Trientine/ur [Urine];*Zinc/ch [Chemistry];0 (Coordination Complexes);0 (Ions);0 (Ligands);0 (Protons);789U1901C5 (Copper);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Nurchi, V. M.;Crisponi, G.;Crespo-Alonso, M.;Lachowicz, J. I.;Szewczuk, Z.;Cooper, G. J.",2013,May 07,https://dx.doi.org/10.1039/c2dt32252h,0,0,
172,A novel HPLC-electrochemical detection approach for the determination of D-penicillamine in skin specimens,"D-penicillamine is a thiol drug mainly used for Wilson's disease, rheumatoid arthritis and cystinuria. Adverse effects during normal use of the drug are frequent and may include skin lesions. To evaluate its toxic effects in clinical cases an original method based on high performance liquid chromatography coupled to amperometric detection in a specific biological matrix such as skin has been developed. The chromatographic analysis of D-penicillamine was carried out on a C18 column using a mixture of acid phosphate buffer and methanol as the mobile phase. Satisfactory sensitivity was obtained by oxidizing the molecule at +0.95 V with respect to an Ag/AgCl reference electrode. A chemical reduction of D-penicillamine-protein disulphide bonds using dithioerythritol combined with microwaves was necessary for the determination of the total amount of D-penicillamine in skin specimens. A further solid-phase extraction procedure on C18 cartridges was implemented for the sample clean-up. The whole analytical procedure was validated: high extraction yield (>91.0%) and satisfactory precision (RSD<6.8%) values were obtained. It was successfully applied to skin samples from a patient who was previously under a long-term, high-dose treatment with the drug and presented serious D-penicillamine-related dermatoses. Thus, the method seems to be suitable for the analysis of D-penicillamine in skin tissues. Copyright © 2012 Elsevier B.V. All rights reserved.","Case-Control Studies;*Chromatography, High Pressure Liquid;Disulfides/ch [Chemistry];Disulfides/me [Metabolism];*Electrochemistry;Electrodes;Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Middle Aged;Penicillamine/ae [Adverse Effects];*Penicillamine/an [Analysis];Penicillamine/ch [Chemistry];*Skin/me [Metabolism];Skin Diseases/ci [Chemically Induced];*Skin Diseases/me [Metabolism];Solid Phase Extraction;0 (Disulfides);GNN1DV99GX (Penicillamine)","Saracino, M. A.;Cannistraci, C.;Bugamelli, F.;Morganti, E.;Neri, I.;Balestri, R.;Patrizi, A.;Raggi, M. A.",2013,Jan 15,https://dx.doi.org/10.1016/j.talanta.2012.10.076,0,0,
173,Lithium treatment of a bipolar patient with Wilson's disease: a case report,"We present the case of a male patient with a family history of both bipolar disorder (BD) and Wilson's disease (WD). Wilson's disease was diagnosed for this patient in 2008, at the age of 28 years, and shortly thereafter his bipolar illness began with depressive episodes. The patient has been treated with zinc sulphate for WD and with antidepressants for depression. In 2009, lithium was added, and in 2010 antidepressants were discontinued. During treatment with zinc sulphate, a gradual improvement of hepatic indices and a decrease of mandibulofacial dystonia was noted. In 2011, a hypomanic state occurred which subsided with an increase of the lithium dose. Since then, the patient has been mostly in a euthymic mood with subclinical hypomanic periods. We suggest that lithium may be a viable option for treating bipolar illness in patients with Wilson's disease. Copyright © Georg Thieme Verlag KG Stuttgart . New York.",Adult;*Antimanic Agents/tu [Therapeutic Use];Bipolar Disorder/co [Complications];*Bipolar Disorder/dt [Drug Therapy];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lithium Chloride/tu [Therapeutic Use];Male;0 (Antimanic Agents);G4962QA067 (Lithium Chloride),"Rybakowski, J. K.;Litwin, T.;Chlopocka-Wozniak, M.;Czlonkowska, A.",2013,May,https://dx.doi.org/10.1055/s-0032-1323784,0,0,
174,Histologic evolution and long-term outcome of Wilson's disease: results of a single-center experience,"BACKGROUND/AIMS: Wilson's disease (WD) is a rare inborn disease related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. The aim of this study was to determine the clinical presentation and long-term outcome, and to examine the progression of hepatic histopathology in serial liver biopsies from WD patients. MATERIALS AND METHODS: We carried out a retrospective analysis of 60 patients with WD treated with zinc and/or penicillamine. Demographic, clinical, and laboratory data were gathered and 40 patients underwent an initial biopsy and at least one repeat biopsy. Patients were divided into two groups: progressors (patients who presented worsening of at least one unit of fibrosis) and nonprogressors (patients who presented stable or improved fibrosis scores). RESULTS: A total of 33/40 (83%) patients (nonprogressors) showed stable hepatic histology or improvement. Seven of 40 (17%) patients (progressors) showed worsening of fibrosis. There was no significant correlation between the histological findings and clinical parameters or initial presentation. CONCLUSION: In our study cohort, liver disease was stable or improving in most of the patients, and development of progressive hepatic symptoms while under treatment was a rare event. The development of new symptoms while under treatment or progression of pre-existing symptoms was more often recorded for neurological than for hepatic symptoms.","Adolescent;Adult;Biopsy;Chelating Agents/tu [Therapeutic Use];Chi-Square Distribution;Child;Child, Preschool;Disease Progression;Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Italy;Liver/de [Drug Effects];*Liver/pa [Pathology];Liver Cirrhosis/dt [Drug Therapy];Liver Cirrhosis/et [Etiology];*Liver Cirrhosis/pa [Pathology];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Retrospective Studies;Time Factors;Treatment Outcome;Trientine/tu [Therapeutic Use];Young Adult;Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Sini, M.;Sorbello, O.;Sanna, F.;Battolu, F.;Civolani, A.;Fanni, D.;Faa, G.;Demelia, L.",2013,Jan,https://dx.doi.org/10.1097/MEG.0b013e328358f7da,1,1,
175,Do we need authorized orphan drugs when compounded medications are available?,"WHAT IS KNOWN AND OBJECTIVE: Orphan drugs are used to diagnose, prevent or treat a rare disease. This Commentary aims to present a number of case studies questioning the need for designating compounded medications with a long history of effective use, which is well-supported by published clinical evidence. COMMENT: Prior to the market introduction of orphan drugs, medication compounding was done in our hospital pharmacy for several rare diseases. Examples include amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (Firdapse()), ibuprofen for the treatment of neonatal patent ductus arteriosus (Pedea()) and zinc acetate for the treatment of Wilson's disease (Wilzin()). Several 'non-orphan' pharmaceutical products, used off-label for the treatment of rare diseases, that became orphan medicinal products include Hydrea() for the treatment of sickle-cell syndrome (Siklos()) and Viagra() for the treatment of pulmonary arterial hypertension (Revatio()). WHAT IS NEW AND CONCLUSION: In our opinion, as indicated by our examples, a better balance should be struck between the development of orphan drugs along the recently established regulatory pathways and the pragmatic use of pharmacy-compounded products and evidence-based off-label use of already available commercial products. Societal needs would be best met by focusing orphan drug development on rare diseases for which there is a high unmet medical need. Copyright © 2012 Blackwell Publishing Ltd.",*Drug Compounding/mt [Methods];*Drug Design;European Union;Health Services Needs and Demand;Humans;Off-Label Use;Orphan Drug Production/lj [Legislation & Jurisprudence];*Orphan Drug Production/mt [Methods];Pharmaceutical Services/og [Organization & Administration];*Rare Diseases/dt [Drug Therapy],"Dooms, M.;Pince, H.;Simoens, S.",2013,Feb,https://dx.doi.org/10.1111/jcpt.12006,0,0,
176,An unusual cause of headache and hypertension,"Children with both headache and hypertension present a relatively rare condition with a broad range of differential diagnoses in pediatric emergency medicine. Some possible diagnoses are potentially life-threatening conditions and merit aggressive evaluation management. We report a case of a 14-year-old girl who presented with headache and hypertension. She responded poorly to medical treatment and subsequently developed anxiety and difficulties with concentration. Three months later, she visited our ophthalmology department because of blurred vision. Ophthalmic evaluation revealed bilateral Kayser-Fleischer rings. Finally, she was diagnosed with Wilson disease. This case emphasizes that children with headache and hypertension merit aggressive evaluation and management.","Adolescent;Chelating Agents/tu [Therapeutic Use];Diagnosis, Differential;Female;Headache/di [Diagnosis];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Hypertension/di [Diagnosis];Trientine/tu [Therapeutic Use];0 (Chelating Agents);SJ76Y07H5F (Trientine)","Hsiao, H. J.;Lin, J. L.;Wu, C. T.;Lin, J. J.;Hsia, S. H.",2013,Jan,https://dx.doi.org/10.1016/j.ajem.2012.05.010,0,0,
177,Wilson disease,"Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism, resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. The leading neurologic symptoms in WD are dysathria, dyspraxia, ataxia, and Parkinsonian-like extrapyramidal signs. Changes in the basal ganglia in brain magnetic resonance imaging (MRI) are characteristic features of the disease. In presence of liver cirrhosis, some features may resemble hepatic encephalopathy. Symptoms and MRI abnormalities may be fully reversible on treatment with zinc or copper chelators. Improvement can be monitored by serial recording of brain-stem-evoked responses. The basic defect is an impaired trafficking of copper in hepatocytes. ATP7B is the gene product of the WD gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. While about 40% of patients preset with neurologic symptoms, little is known about the role of copper and ATP7B in the central nervous system. In some brain areas, like in the pineal gland, ATP7B is expressed and functionally active. Increasing evidence supports an important role for metals in neurobiology. Two proteins related to neurodegeneration are copper-binding proteins (1) the amyloid precursor protein (APP), a protein related to Alzheimer's disease, and (2) the Prion protein, related to Creutzfeldt-Jakob disease. A major source of free-radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. APP is a major regulator of neuronal copper homeostasis and has a copper-binding domain (CuBD). The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. There are several copper-containing enzymes in the brain, like dopamine beta hydroxylase or Cu/Zn superoxide dismutase (SOD1). Their function may be altered because of copper overload. WD appears to be associated with a dopaminergic deficit. Mutations in the SOD1gene cause familial amyotrophic lateral sclerosis. Survival of transgenic mice with a mutant SOD1 which fails to incorporate Cu((2+)) in its active site was improved by copper depletion. Wilson disease (WD) is an autosomal recessive inherited disorder in which copper pathologically accumulates primarily within the liver and subsequently in the neurologic system and many other organs and tissues. Presence of liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings are the hallmarks of the disease. [References: 43]",Animals;Brain/pa [Pathology];Copper/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/px [Psychology];Humans;Liver/me [Metabolism];789U1901C5 (Copper),"Kitzberger, R.;Madl, C.;Ferenci, P.",2005,Dec,https://dx.doi.org/10.1007/s11011-005-7910-8,0,0,
178,Pathophysiology and clinical features of Wilson disease,"Wilson disease is an autosomal recessive inherited disorder of copper metabolism resulting in pathological accumulation of copper in many organs and tissues. ATP7B is the gene product of the Wilson disease gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. Mutations of the gene result in impaired trafficking of copper in and through the hepatocytes. More than 200 mutations of Wilson disease gene were found, the most common ones being H1069Q (in Europe) and R778L (in Asia). Wilson disease may present under a variety of clinical conditions, commonly as liver and/or neuropsychiatric disease. The pathogenesis of hepatic and neurologic Wilson disease is a direct consequence of copper accumulation. Presence of copper causes oxidative stress resulting in cell destruction. The diagnosis of Wilson disease requires a combination of a variety of clinical symptoms, biochemical tests, and detection of gene mutations, which are the basis of a score proposed by a group of international experts. Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine). Treatment of presymptomatic patients or maintenance therapy can also be accomplished with zinc. [References: 60]",*Adenosine Triphosphatases/ge [Genetics];Brain/me [Metabolism];Brain/pp [Physiopathology];*Cation Transport Proteins/ge [Genetics];Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];*Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;Liver/me [Metabolism];Liver/pp [Physiopathology];*Mutation/ge [Genetics];Oxidative Stress/ge [Genetics];Zinc/tu [Therapeutic Use];0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc),"Ferenci, P.",2004,Dec,,0,0,
179,Pyridoxal isonicotinoyl hydrazone (PIH) prevents copper-mediated in vitro free radical formation,"Pyridoxal isonicotinoyl hydrazone (PIH) is an iron chelator with antioxidant activity, low toxicity and is useful in the experimental treatment of iron-overload diseases. Previous studies on x-ray diffraction have revealed that PIH also forms a complex with Cu(II). Since the main drug of choice for the treatment of Wilson's disease, d-penicillamine, causes a series of side effects, there is an urgent need for the development of alternative copper chelating agents for clinical use. These chelators must also have antioxidant activity because oxidative stress is associated with brain and liver copper-overload. In this work we tested the ability of PIH to prevent in vitro free radical formation mediated by Cu(II), ascorbate and dissolved O2. Degradation of 2-deoxyribose mediated by 10 microM Cu(II) and 3 mM ascorbate was fully inhibited by 10 microM PIH (I50 = 6 microM) or 20 microM d-penicillamine (I50 = 10 microM). The antioxidant efficiency of PIH remained unchanged with increasing concentrations (from 1 to 15 mM) of the hydroxyl radical detector molecule, 2-deoxyribose, indicating that PIH does not act as a hydroxyl scavenger. On the other hand, the efficiency of PIH (against copper-mediated 2-deoxyribose degradation and ascorbate oxidation) was inversely proportional to the Cu(II) concentration, suggesting a competition between PIH and ascorbate for complexation with Cu(lI). An almost full inhibitory effect by PIH was observed when the ratio PIH:copper was 1:1. A similar result was obtained with the measurement of copper plus ascorbate-mediated O2 uptake. Moreover, spectral studies of the copper and PIH interaction showed a peak at 455 nm and also indicated the formation of a stable Cu(II) complex with PIH with a 1:1 ratio. These data demonstrated that PIH prevents hydroxyl radical formation and oxidative damage to 2-deoxyribose by forming a complex with Cu(II) that is not reactive with ascorbate (first step of the reactions leading to hydroxyl radical formation from Cu(II), ascorbate and O2) and does not participate in Haber-Weiss reactions.",Ascorbic Acid/pd [Pharmacology];*Copper Sulfate/ai [Antagonists & Inhibitors];Copper Sulfate/pd [Pharmacology];Deoxyribose/me [Metabolism];*Free Radical Scavengers/pd [Pharmacology];Free Radicals;*Hydroxyl Radical/ai [Antagonists & Inhibitors];Hydroxyl Radical/me [Metabolism];In Vitro Techniques;*Iron Chelating Agents/pd [Pharmacology];*Isoniazid/aa [Analogs & Derivatives];*Isoniazid/pd [Pharmacology];Kinetics;Oxidation-Reduction;Oxygen/me [Metabolism];*Pyridoxal/aa [Analogs & Derivatives];*Pyridoxal/pd [Pharmacology];0 (Free Radical Scavengers);0 (Free Radicals);0 (Iron Chelating Agents);3352-57-6 (Hydroxyl Radical);3THM379K8A (Pyridoxal);533-67-5 (Deoxyribose);737-86-0 (pyridoxal isonicotinoyl hydrazone);LRX7AJ16DT (Copper Sulfate);PQ6CK8PD0R (Ascorbic Acid);S88TT14065 (Oxygen);V83O1VOZ8L (Isoniazid),"Hermes-Lima, M.;Goncalves, M. S.;Andrade, R. G., Jr.",2001,Dec,,0,0,
180,Structural and functional insights of Wilson disease copper-transporting ATPase,"Wilson disease is an autosomal recessive disorder of copper metabolism. The gene for this disorder has been cloned and identified to encode a copper-transporting ATPase (ATP7B), a member of a large family of cation transporters, the P-type ATPases. In addition to the core elements common to all P-type ATPases, the Wilson copper-transporting ATPase has a large cytoplasmic N-terminus comprised six heavy metal associated (HMA) domains, each of which contains the copper-binding sequence motif GMT/HCXXC. Extensive studies addressing the functional, regulatory, and structural aspects of heavy metal transport by heavy metal transporters in general, have offered great insights into copper transport by Wilson copper-transporting ATPase. The findings from these studies have been used together with homology modeling of the Wilson disease copper-transporting ATPases based on the X-ray structure of the sarcoplasmic reticulum (SR) calcium-ATPase, to present a hypothetical model of the mechanism of copper transport by copper-transporting ATPases. [References: 67]","Adenosine Triphosphatases/ch [Chemistry];*Adenosine Triphosphatases/ge [Genetics];*Adenosine Triphosphatases/me [Metabolism];Amino Acid Sequence;Binding Sites;Calcium-Transporting ATPases/ch [Chemistry];Cation Transport Proteins/ch [Chemistry];*Cation Transport Proteins/ge [Genetics];*Cation Transport Proteins/me [Metabolism];*Copper/me [Metabolism];Hepatolenticular Degeneration/en [Enzymology];*Hepatolenticular Degeneration/ge [Genetics];Humans;Kinetics;Models, Molecular;Protein Structure, Secondary;Sarcoplasmic Reticulum Calcium-Transporting ATPases;Zinc/me [Metabolism];0 (Cation Transport Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);EC 3-6-3-8 (Calcium-Transporting ATPases);EC 3-6-3-8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases);J41CSQ7QDS (Zinc)","Fatemi, N.;Sarkar, B.",2002,Oct,,0,0,
181,"Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients","The aim of the study is to evaluate the serum copper, ceruloplasmin and 24-h urine copper levels in celiac patients. Serum copper, ceruloplasmin and 24-h urine measurements were evaluated in patients with celiac (n = 32), Crohn's (n = 25), Wilson's (n = 11) and in a healthy group (n = 35). Serum and 24-h urine zinc levels, AST, ALT, BUN, creatinine, iron, hemoglobin, hematocrit, lymphocyte, sedimentation and CRP levels were also measured. Results were evaluated statistically and significance was accepted as meaningful if P < 0.05. In celiacs, levels of urine copper were high (52 +/- 29 microg/day, P < 0.000) but serum copper was the same as in controls (105 +/- 16 microg/dl, P < 0.158). High urinary copper of celiacs were coming out in women (56 +/- 30 microg/day) and in man (33 +/- 17 microg/day, P < 0.115). Most celiacs were female (P < 0.001). Serum copper and ceruloplasmin levels in all groups were higher in women than in men and this was meaningful for serum copper in the control group (P < 0.045) and for ceruloplasmin in Crohn's (P < 0.055) and control groups (P < 0.031). Serum (70 +/- 14 microg/dl, P < 0.000) and urine zinc levels (25 +/- 15 microg/dl, P < 0.039) of celiacs were low. Ceruloplasmin levels were higher in celiacs (337 +/- 64 U/1) and Crohn's patients (366 +/- 47 U/l, P < 0.000). Correlations observed in the groups of celiac (P < 0.029) and Crohn's (P < 0.024), celiac and Wilson's (P < 0.001) and Crohn's and Wilson's (P < 0.001) between the ceruloplasmin and 24-h urine copper parameters. AST and ALT levels were higher in celiac and Wilson's patients than in Crohn's patients and controls. Mean CRP levels were significantly higher in Crohn's than others. Lymphocyte counts were meaningfully higher in celiacs. Statistically, while mean iron, hemoglobulin and hematocrit levels of celiac and Crohn groups were meaningfully lower than the normal and Wilson's group, it was similar in Wilson's and the control group. Serum copper (85 +/- 26 microg/dl, P < 0.158) and ceruloplasmin (219 +/- 83 U/l, P < 0.001) levels were low and 24-h urine copper levels were high (415 +/- 346 microg/day) in Wilson's group. Increased urinary loss may be another cause of copper deficiency in female celiacs besides malabsorption and this topic needs more investigation. Increased urinary copper levels in celiac women should not always be regarded as a diagnosis of Wilson's disease.","Adult;Case-Control Studies;*Celiac Disease/bl [Blood];*Celiac Disease/ur [Urine];*Ceruloplasmin/me [Metabolism];Chi-Square Distribution;*Copper/bl [Blood];*Copper/ur [Urine];Crohn Disease/bl [Blood];Crohn Disease/ur [Urine];Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/ur [Urine];Humans;Male;Sex Factors;Statistics, Nonparametric;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin)","Ince, A. T.;Kayadibi, H.;Soylu, A.;Ovunc, O.;Gultepe, M.;Toros, A. B.;Yasar, B.;Kendir, T.;Abut, E.",2008,Jun,https://dx.doi.org/10.1007/s10620-007-0043-7,0,0,
182,Liver structures of a patient with idiopathic copper toxicosis,"This is the first report describing the liver structures of a Japanese patient with idiopathic copper toxicosis, which should be differentiated from hepatolenticular degeneration of Wilson disease. An 11-year-old Japanese boy presented with ascites associated with biochemical liver damage. Involvement of hepatitis virus was ruled out by laboratory tests. Because urinary copper excretion was increased, Wilson disease was highly suspected, but the serum level of ceruloplasmin was normal, and Kayser-Fleischer rings were not detected by slit lamp examination. Brain images were within normal limits. ATP7B analysis was negative for mutations. Liver specimen showed cirrhosis associated with chronic active hepatitis. Almost all hepatocytes were positive for orcein-stained granules. Mallory bodies were found in some hepatocytes. Fatty change was minimal, and there were no glycogenated nuclei in the parenchyma. Combined regimens of trientine and zinc for 6 months improved the decompensated state of liver function. After 2.5 years of treatment, a second liver biopsy was performed. The post-treatment liver showed complete disappearance of portal inflammation and remarkable decrease in cuprothionein granules. Mallory bodies disappeared from the parenchyma. An abundance of hepatocellular Mallory bodies and heavy copper loading limited to the liver may be specific to idiopathic copper toxicosis.","Ascites/di [Diagnosis];Ascites/et [Etiology];Chelating Agents/tu [Therapeutic Use];Child;*Copper/po [Poisoning];Diagnosis, Differential;Hepatocytes/pa [Pathology];Humans;*Liver/de [Drug Effects];Liver/pa [Pathology];*Liver Diseases/di [Diagnosis];Liver Diseases/et [Etiology];Male;Mallory Bodies/pa [Pathology];Treatment Outcome;Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);SJ76Y07H5F (Trientine)","Hayashi, H.;Shinohara, T.;Goto, K.;Fujita, Y.;Murakami, Y.;Hattori, A.;Tatsumi, Y.;Shimizu, A.;Ichiki, T.",2012,Jun,https://dx.doi.org/10.1007/s00795-011-0556-1,0,0,
183,D-Penicillamine improved laparoscopic and histological findings of the liver in a patient with Wilson's disease: 3-year follow-up after diagnosis of Coombs-negative hemolytic anemia of Wilson's disease,"We report a 13-year-old girl who presented with hepatic failure and hemolytic anemia. Laboratory findings showed a normal serum copper level (104 microg/dl), high urinary copper level (2370 microg/dl), and low serum ceruloplasmin level (14.3 microg/dl). Slit-lamp examination revealed Kayser-Fleischer rings on her cornea, and she was diagnosed with Wilson's disease. Plasma exchange and continuous hemodiafiltration relieved the serious condition, after that laparoscopic examination was performed. Administration of D-penicillamine and restriction of dietary copper (<1 mg/day) were started, leading to a normalized serum alanine amino transferase (ALT) level. After 3 years, she again underwent laparoscopic examination, and the laparoscopic and histological findings of her liver were obviously improved. Management of the copper level can reverse severe liver fibrosis in Wilson's disease.","Adolescent;*Anemia, Hemolytic/co [Complications];Anemia, Hemolytic/dt [Drug Therapy];Anemia, Hemolytic/me [Metabolism];*Antidotes/tu [Therapeutic Use];Biopsy;*Coombs Test;Copper/me [Metabolism];Female;Follow-Up Studies;Hemodiafiltration;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/th [Therapy];Humans;*Laparoscopy;Liver/me [Metabolism];Liver/pa [Pathology];*Liver Failure/dt [Drug Therapy];Liver Failure/et [Etiology];Liver Failure/pa [Pathology];*Penicillamine/tu [Therapeutic Use];Photomicrography;Time Factors;0 (Antidotes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Sakaida, I.;Kawaguchi, K.;Kimura, T.;Tamura, F.;Okita, K.",2005,Jun,https://dx.doi.org/10.1007/s00535-005-1600-5,0,0,
184,Gross hematuria in a case of Wilson disease: answers,,"Acidosis, Renal Tubular/di [Diagnosis];Acidosis, Renal Tubular/dt [Drug Therapy];*Acidosis, Renal Tubular/et [Etiology];Bicarbonates/tu [Therapeutic Use];Chelating Agents/tu [Therapeutic Use];Child;*Hematuria/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Hypercalciuria/di [Diagnosis];Hypercalciuria/dt [Drug Therapy];*Hypercalciuria/et [Etiology];Male;Penicillamine/tu [Therapeutic Use];Treatment Outcome;0 (Bicarbonates);0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Sinha, R.;Akhtar, S.",2012,Jun,https://dx.doi.org/10.1007/s00467-011-2011-x,0,0,
185,Wilson's disease-cause of mortality in 164 patients during 1992-2003 observation period,"We studied the cause of death in a consecutive series of 164 patients with Wilson's disease (WD) diagnosed over an 11 year period. A total of 20 [12% (95% CI 10.3-16.0)] died during the observation period. The relative survival rate of all patients in our group was statistically smaller than in Polish population. The main cause of death was the diagnosis in advanced stage of disease, but in six patients presenting with mild signs, we observed the progression of the disease despite treatment. There was no difference in mortality rate in patients treated with d-penicillamine or zinc sulphate as initial therapy. The prognosis for survival in the majority of WD patients is favourable, provided that therapy is introduced early.",Adult;Brain/de [Drug Effects];Brain/me [Metabolism];Brain/pa [Pathology];Confidence Intervals;Copper/me [Metabolism];Disease Progression;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ep [Epidemiology];*Hepatolenticular Degeneration/mo [Mortality];Humans;Male;*Observation/mt [Methods];Penicillamine/tu [Therapeutic Use];Retrospective Studies;Survival Rate;Treatment Outcome;Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Czlonkowska, A.;Tarnacka, B.;Litwin, T.;Gajda, J.;Rodo, M.",2005,Jun,https://dx.doi.org/10.1007/s00415-005-0720-4,1,1,
186,Improvement of cardiovascular autonomic dysfunction following anti-copper therapy in Wilson's disease,,*Cardiovascular System/de [Drug Effects];Cardiovascular System/pp [Physiopathology];Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];Copper/ai [Antagonists & Inhibitors];*Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Magnetic Resonance Imaging/mt [Methods];Middle Aged;Trientine/pd [Pharmacology];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);SJ76Y07H5F (Trientine),"Deguchi, K.;Sasaki, I.;Touge, T.;Tsukaguchi, M.;Ikeda, K.;Shimamura, M.;Urai, Y.;Watanabe, S.;Takeuchi, H.;Kuriyama, S.",2005,Apr,https://dx.doi.org/10.1007/s00415-005-0674-6,0,0,
187,Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI,"INTRODUCTION: Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. METHODS: Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: D: -penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. RESULTS: MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. CONCLUSIONS: From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P.",Adolescent;Adult;Brain/de [Drug Effects];*Brain/pa [Pathology];*Central Nervous System Agents/pd [Pharmacology];Child;Female;Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Male;*Penicillamine/pd [Pharmacology];Retrospective Studies;Treatment Outcome;Young Adult;*Zinc Compounds/pd [Pharmacology];0 (Central Nervous System Agents);0 (Zinc Compounds);GNN1DV99GX (Penicillamine),"da Costa Mdo, D.;Spitz, M.;Bacheschi, L. A.;Leite, C. C.;Lucato, L. T.;Barbosa, E. R.",2009,Oct,https://dx.doi.org/10.1007/s00234-009-0536-5,0,1,
188,'Face of the giant panda' sign in Wilson disease,,Adolescent;Arm/pp [Physiopathology];Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Dystonia/et [Etiology];Follow-Up Studies;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Magnetic Resonance Imaging/mt [Methods];Male;Penicillamine/tu [Therapeutic Use];Trace Elements/tu [Therapeutic Use];Tremor/et [Etiology];Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Thapa, R.;Ghosh, A.",2008,Dec,https://dx.doi.org/10.1007/s00247-008-1017-4,0,0,
189,Copper transport and Alzheimer's disease,"This brief review discusses copper transport in humans, with an emphasis on knowledge learned from one of the simplest model organisms, yeast. There is a further focus on copper transport in Alzheimer's Disease (AD). Copper homeostasis is essential for the well-being of all organisms, from bacteria to yeast to humans: survival depends on maintaining the required supply of copper for the many enzymes, dependent on copper for activity, while ensuring that there is no excess free copper, which would cause toxicity. A virtual orchestra of proteins are required to achieve copper homeostasis. For copper uptake, Cu(II) is first reduced to Cu(I) via a membrane-bound reductase. The reduced copper can then be internalised by a copper transporter where it is transferred to copper chaperones for transport and specific delivery to various organelles. Of significance are internal copper transporters, ATP7A and ATP7B, notable for their role in disorders of copper deficiency and toxicity, Menkes and Wilson's disease, respectively. Metallothioneins and Cu/Zn superoxide dismutase can protect against excess copper in cells. It is clear too, increasing age, environmental and lifestyle factors impact on brain copper. Studies on AD suggest an important role for copper in the brain, with some AD therapies focusing on mobilising copper in AD brains. The transport of copper into the brain is complex and involves numerous players, including amyloid precursor protein, A beta peptide and cholesterol. [References: 58]","Adenosine Triphosphatases/me [Metabolism];*Alzheimer Disease/me [Metabolism];Alzheimer Disease/pp [Physiopathology];Amyloid beta-Peptides/me [Metabolism];Amyloid beta-Protein Precursor/me [Metabolism];*Biological Transport;Brain/pp [Physiopathology];Cation Transport Proteins/me [Metabolism];Cholesterol/me [Metabolism];*Copper/me [Metabolism];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];Homeostasis;Humans;Menkes Kinky Hair Syndrome/me [Metabolism];Menkes Kinky Hair Syndrome/pp [Physiopathology];*Metalloproteins/me [Metabolism];Organic Cation Transport Proteins;Oxidoreductases/me [Metabolism];Saccharomyces cerevisiae/me [Metabolism];0 (Amyloid beta-Peptides);0 (Amyloid beta-Protein Precursor);0 (Cation Transport Proteins);0 (Metalloproteins);0 (Organic Cation Transport Proteins);789U1901C5 (Copper);97C5T2UQ7J (Cholesterol);EC 1 (Oxidoreductases);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (ATP7A protein, human);EC 3-6-3-4 (Wilson disease protein)","Macreadie, I. G.",2008,Mar,https://dx.doi.org/10.1007/s00249-007-0235-2,0,0,
190,Clinical correlation of brain MRI and MRS abnormalities in patients with Wilson disease,"BACKGROUND: The progression of Wilson disease (WD), a disorder of copper metabolism, can be arrested by chelation therapy. However, neurologic deficits may persist despite adequate treatment. MRI is used to assess patients with WD, but previous attempts to correlate clinical progression with the investigation findings have often been unsuccessful. OBJECTIVE: To identify MR visible markers that could help stratify disease severity and to clarify the mechanism of persistent neurologic deficit after treatment. METHODS: MRI and proton MR spectroscopy (1H-MRS) were performed in 17 patients with WD. MRI was assessed semiquantitatively and used to locate volumes of interest (voxels) in the striatum for 1H-MRS. RESULTS: MRI showed abnormalities predominantly confined to those patients with neurologic features of WD. The 1H spectra demonstrated a reduction of N-acetylaspartate and N-acetylaspartylglutamate (2.05 mM; p < 0.01) in those patients with neurologic features but not in patients without clinical neurologic involvement (0.42 mM; p > 0.1) in comparison with age-matched normal control subjects. Choline was also reduced in both patient groups (0.08 mM; p < 0.01) compared with age-matched controls. CONCLUSIONS: There may be a biochemical correlate of tissue-specific dysfunction in patients with Wilson disease who develop neurologic features. These changes appear to be present despite prior clinical improvement and may imply a need for additional treatment.",Adult;Aged;*Aspartic Acid/aa [Analogs & Derivatives];*Aspartic Acid/an [Analysis];Atrophy;*Brain/pa [Pathology];*Brain Chemistry;Chelation Therapy;Copper;*Dipeptides/an [Analysis];Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Mitochondria/me [Metabolism];Mitochondria/pa [Pathology];Nervous System Diseases/et [Etiology];Penicillamine/tu [Therapeutic Use];Severity of Illness Index;Single-Blind Method;Trientine/tu [Therapeutic Use];0 (Dipeptides);1W8M12WXYL (isospaglumic acid);30KYC7MIAI (Aspartic Acid);789U1901C5 (Copper);997-55-7 (N-acetylaspartate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Page, R. A.;Davie, C. A.;MacManus, D.;Miszkiel, K. A.;Walshe, J. M.;Miller, D. H.;Lees, A. J.;Schapira, A. H.",2004,Aug 24,,0,0,
191,Nuclear magnetic resonance brain study in a case of Wilson disease,,Adolescent;*Brain/pa [Pathology];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Spectroscopy;Male;Penicillamine/tu [Therapeutic Use];Pyridoxine/tu [Therapeutic Use];Sulfates/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);KV2JZ1BI6Z (Pyridoxine),"Longhi, R.;Riva, E.;Rottoli, A.;Valsasina, R.;Pinelli, P.;Giovannini, M.",1989,,,0,0,
192,Wilson's disease and pregnancy. A case report,,"Abortion, Spontaneous;Adult;Ascites/et [Etiology];Autopsy;Ceruloplasmin/bl [Blood];Copper/bl [Blood];Diet Therapy;Female;Fetus/de [Drug Effects];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Hepatomegaly/et [Etiology];Humans;Kidney Diseases/et [Etiology];Liver Cirrhosis/et [Etiology];Penicillamine/tu [Therapeutic Use];Portal Vein;Pregnancy;*Pregnancy Complications;Remission, Spontaneous;Thrombosis/et [Etiology];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Albukerk, J. N.",1973,Jun,,0,0,
193,Triethylene tetramine dihydrochloride in Wilson's disease,,Adolescent;*Ethylenediamines/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;0 (Ethylenediamines),"Dubois, R. S.;Rodgerson, D. O.;Slovis, T. L.;Hambidge, K. M.;Bianchi, T. A.",1970,Oct 10,,0,0,
194,Prevention of Wilson's disease by penicillamine?,,"Ceruloplasmin/bl [Blood];Child, Preschool;Copper/ur [Urine];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pc [Prevention & Control];Homozygote;Humans;Liver/an [Analysis];*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)",Anonymous,1968,May 11,,0,0,
195,Penicillamine for tubular dysfunction in Wilson's disease,,*Acute Kidney Injury/dt [Drug Therapy];Acute Kidney Injury/et [Etiology];Amino Acids/bl [Blood];Child;*Hepatolenticular Degeneration/co [Complications];Humans;Kidney Function Tests;Kidney Tubules/me [Metabolism];Male;*Penicillamine/tu [Therapeutic Use];0 (Amino Acids);GNN1DV99GX (Penicillamine),"Troelstra, J. A.;Holl, H.",1968,May 18,,0,0,
196,Effect of penicillamine on failure of renal acidification in Wilson's disease,,Adolescent;Adult;*Ammonia/me [Metabolism];Ammonium Chloride;Ceruloplasmin/bl [Blood];Child;Copper/bl [Blood];*Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Hydrogen-Ion Concentration;*Kidney/pp [Physiopathology];Kidney Function Tests;Male;*Penicillamine/tu [Therapeutic Use];01Q9PC255D (Ammonium Chloride);7664-41-7 (Ammonia);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1968,Apr 13,,0,0,
197,Penicillamine and pyridoxine requirements in man,,"Adult;Animals;Child;Chromatography, Paper;Epilepsies, Partial/et [Etiology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Injections, Intraperitoneal;Male;Middle Aged;*Penicillamine/ae [Adverse Effects];Rats;*Tryptophan/me [Metabolism];Urine;*Vitamin B 6 Deficiency/et [Etiology];*Xanthurenates/me [Metabolism];0 (Xanthurenates);8DUH1N11BX (Tryptophan);GNN1DV99GX (Penicillamine)","Gibbs, K.;Walshe, J. M.",1966,Jan 22,,0,0,
198,Preparation of triethylenetetramine dihydrochloride for the treatment of Wilson's disease,,*Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Methods;*Piperidines/tu [Therapeutic Use];Quaternary Ammonium Compounds/tu [Therapeutic Use];0 (Chelating Agents);0 (Piperidines);0 (Quaternary Ammonium Compounds),"Dixon, H. B.;Gibbs, K.;Walshe, J. M.",1972,Apr 15,,0,0,
199,Lupus-like syndrome induced by D-penicillamine in Wilson's disease,,"Adult;Antigen-Antibody Reactions;Arthritis, Rheumatoid;Autoantibodies;Cystinuria;Female;Haptens;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Hypersensitivity, Delayed;Leukocytes/an [Analysis];Lupus Vulgaris/ci [Chemically Induced];Lupus Vulgaris/co [Complications];*Penicillamine/ae [Adverse Effects];0 (Autoantibodies);0 (Haptens);GNN1DV99GX (Penicillamine)","Harpey, J. P.;Caille, B.;Moulias, R.;Goust, J. M.",1971,Feb 06,,0,0,
200,Endocrine studies of the ovulatory disturbances in Wilson's disease (hepatolenticular degeneration),"Women with Wilson's disease may have severe oligomenorrhea or amenorrhea whose cause is unknown. The endocrine profile of four such cases was investigated by measuring basal values and the response to dynamic tests of hypothalamic, pituitary, thyroid, and adrenal function, which all proved normal. Ovarian function was disturbed, as witnessed by low estradiol, high total testosterone (T) levels with normal free T, and mildly elevated androstenedione. An interference of ovarian follicular aromatase activity possibly due to copper intoxication could explain these findings as the cause of the ovulatory disturbances of Wilson's disease.",Adolescent;Adult;Amenorrhea/bl [Blood];Amenorrhea/et [Etiology];Androstenedione/bl [Blood];Estradiol/bl [Blood];Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Oligomenorrhea/bl [Blood];Oligomenorrhea/et [Etiology];Ovarian Function Tests/mt [Methods];*Ovary/se [Secretion];Penicillamine/tu [Therapeutic Use];Testosterone/bl [Blood];3XMK78S47O (Testosterone);409J2J96VR (Androstenedione);4TI98Z838E (Estradiol);GNN1DV99GX (Penicillamine),"Kaushansky, A.;Frydman, M.;Kaufman, H.;Homburg, R.",1987,Feb,,0,0,
201,Compliance and Wilson's disease,,Adolescent;*Attitude of Health Personnel;Dementia/et [Etiology];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Patient Compliance;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Emery, P.;Mackay, I. R.",1986,Jun 14,,0,0,
202,[Electrophysiological impairment profile of patients with Wilson's disease],"In addition to hepatic and extrapyramidal motor clinical symptoms, Wilson's disease patients also exhibit subclinical disorders of other central nervous pathways. In this study, an impairment profile is described by means of eight electrophysiological tests (EAEP, MSEP, TSEP, T-VEP, MEP, EEG, heart frequency variability, and SSR) for 37 patients (28 with neurological, nine with tnon-neurological form) undergoing long-term drug therapy. The occurrence in 64.3% of a delayed wave III and/or IPL III-V prolongation in patients with the neurological form makes pathological FAEP the most common form of the disorder, followed by disorders in MSEP, TSEP, MEP, and T-VEP. Patients with the non-neurological form usually have normal values, although latency prolongations occur in isolated cases. The range of evoked potential findings is characterised primarily by latency prolongations, i.e. a demyelinising impairment type, and significant losses of potential hardly occur (except in the MEP). The electrophysiological impairment profile does not include EEG changes or vegetative disorders.","Autonomic Nervous System Diseases/di [Diagnosis];Autonomic Nervous System Diseases/dt [Drug Therapy];Autonomic Nervous System Diseases/pp [Physiopathology];Basal Ganglia Diseases/di [Diagnosis];Basal Ganglia Diseases/dt [Drug Therapy];*Basal Ganglia Diseases/pp [Physiopathology];Cerebral Cortex/de [Drug Effects];Cerebral Cortex/pp [Physiopathology];Chelating Agents/tu [Therapeutic Use];Diagnosis, Differential;Electric Stimulation;Extrapyramidal Tracts/de [Drug Effects];Extrapyramidal Tracts/pp [Physiopathology];Galvanic Skin Response/de [Drug Effects];Galvanic Skin Response/ph [Physiology];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Nervous System Diseases/di [Diagnosis];Nervous System Diseases/dt [Drug Therapy];*Nervous System Diseases/pp [Physiopathology];Neurologic Examination;*Penicillic Acid/aa [Analogs & Derivatives];Penicillic Acid/tu [Therapeutic Use];Peripheral Nerves/de [Drug Effects];Peripheral Nerves/pp [Physiopathology];Reaction Time/de [Drug Effects];Reaction Time/ph [Physiology];Trientine/tu [Therapeutic Use];0 (Chelating Agents);34138-28-8 (penicillamide);ONL14K3AFD (Penicillic Acid);SJ76Y07H5F (Trientine)","Hermann, W.;Villmann, T.;Wagner, A.",2003,Oct,https://dx.doi.org/10.1007/s00115-003-1564-8,0,0,
203,Practical recommendations and new therapies for Wilson's disease,"Wilson's disease is an inherited disorder of copper accumulation. The basic defect is a failure of excretion of excess copper in the bile by the liver for loss in the stool. The accumulating copper causes damage primarily to the liver and the brain. Patients typically present in the second to the fourth decades of life with liver disease, a neurological disease of the movement disorder type, or a wide array of behavioural disturbances. Because the manifestations of Wilson's disease are so protean, and the disease masquerades so well as something else, recognition of the possibility of Wilson's disease is a major problem, leading to serious underdiagnosis of the disease. Excellent therapies exist for both the prophylaxis and treatment of Wilson's disease. The longer recognition and diagnosis are delayed, the greater the risk of permanent damage to liver and/or brain. The availability of effective therapy and the risks in delay or therapy make the earliest possible diagnosis critical. Once the disease comes under consideration, a series of diagnostic steps can be undertaken which almost always establish or rule out the diagnosis of Wilson's disease. These include urine copper, blood ceruloplasmin, slit lamp examination for Kayser-Fleischer rings, and liver biopsy with quantitative copper assay. Currently, there are 4 drugs being used as anticopper agents in Wilson's disease. These are zinc, which blocks intestinal absorption of copper, penicillamine and trientine, both of which are chelators that increase urinary excretion of copper, and tetrathiomolybdate which forms a tripartite complex with copper and protein, and can block copper absorption from the intestine, or render blood copper non-toxic. Zinc is clearly the treatment of choice, in our opinion, for maintenance therapy, for the treatment of the presymptomatic patient from the beginning and for the treatment of the pregnant patient, because of its complete efficacy and lack of toxicity. For the initial treatment of the patient presenting with mild liver failure, we empirically use a combination of trientine and zinc. Trientine gives a strong, fast, negative copper balance, and zinc induces hepatic metallothionein, which sequesters hepatic copper. For the initial treatment of patients presenting with neurological disease we use an experimental drug, tetrathiomolybdate, which provides rapid, safe control of copper. These latter patients are at great risk of serious permanent neurological worsening with penicillamine, and zinc is too slow-acting, in our judgment, to be optimal. [References: 46]",*Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/et [Etiology];Humans;Liver/de [Drug Effects];Liver/me [Metabolism];Metallothionein/me [Metabolism];Molybdenum/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Pregnancy;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);9038-94-2 (Metallothionein);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Brewer, G. J.",1995,Aug,,0,1,
204,Current therapy of chronic liver disease,"The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven. [References: 89]",Animals;Chronic Disease;Humans;Liver Diseases/dh [Diet Therapy];*Liver Diseases/dt [Drug Therapy],"Stavinoha, M. W.;Soloway, R. D.",1990,Jun,,0,0,
205,Nephrotic Syndrome Associated with Penicillamine Therapy of Wilson's Disease,,*Biopsy;*Dermatology;*Drug Hypersensitivity;*Glomerulonephritis;*Hepatolenticular Degeneration;Humans;*Kidney;*Nephrotic Syndrome;*Pathology;*Penicillamine;*Prednisone;*Steroids;*Sulfides;*Toxicology;0 (Steroids);0 (Sulfides);GNN1DV99GX (Penicillamine);VB0R961HZT (Prednisone),"Adams, D. A.;Goldman, R.;Maxwell, M. H.;Latta, H.",1964,Feb,,0,0,
206,Copper disposition of the fetus and placenta in a patient with untreated Wilson's disease,A patient with untreated Wilson's disease showed the possibility of fetal liver damage and copper accumulation in the placenta by this disease. This is the first report of copper disposition on the fetus and placenta in a patient with untreated Wilson's disease.,"Adult;Ceruloplasmin/me [Metabolism];*Copper/me [Metabolism];Copper/ur [Urine];Female;*Fetal Diseases/et [Etiology];Fetus/me [Metabolism];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Infant, Newborn;Liver Cirrhosis/em [Embryology];*Liver Cirrhosis/et [Etiology];Male;Penicillamine/tu [Therapeutic Use];*Placenta/me [Metabolism];Pregnancy;*Pregnancy Complications;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Oga, M.;Matsui, N.;Anai, T.;Yoshimatsu, J.;Inoue, I.;Miyakawa, I.",1993,Jul,,0,0,
207,Radiocopper studies in patients with Wilson's disease and their relatives,,*Copper/me [Metabolism];Copper/ur [Urine];Feces;*Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Penicillamine/tu [Therapeutic Use];Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Tauxe, W. N.;Goldstein, N. P.;Randall, R. V.;Gross, J. B.",1966,Sep,,0,0,
208,Pregnancy in a patient with treated Wilson's disease: a case report,"Pregnancy should have a successful outcome in a patient with treated Wilson's disease if complications are excluded before conception. Chelating treatment must be maintained, although there is some concern about its teratogenicity. We describe the course of pregnancy in a patient followed up in our department.",Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications/dt [Drug Therapy];Pregnancy Outcome;GNN1DV99GX (Penicillamine),"Dupont, P.;Irion, O.;Beguin, F.",1990,Nov,,0,0,
209,Kayser-Fleischer rings in a patient with basal cell carcinoma: fortuitous diagnosis of presymptomatic Wilson's disease,"Kayser-Fleischer rings were detected during a routine ophthalmologic workup in a 25-year-old man with basal cell carcinoma of the eyelid. Although the importance of this association is uncertain, the routine preoperative evaluation of basal cell carcinoma led to the presymptomatic diagnosis of Wilson's disease. These disorders are discussed, as are the benefits of a multidisciplinary approach for the diagnosis and management of medical problems.","Adult;Alkaline Phosphatase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Blood Proteins/ch [Chemistry];*Carcinoma, Basal Cell/co [Complications];Carcinoma, Basal Cell/di [Diagnosis];Carcinoma, Basal Cell/su [Surgery];Ceruloplasmin/ch [Chemistry];Copper/ad [Administration & Dosage];Copper/bl [Blood];Copper/ur [Urine];Creatinine/bl [Blood];Diet Therapy;*Eyelid Neoplasms/co [Complications];Eyelid Neoplasms/di [Diagnosis];Eyelid Neoplasms/su [Surgery];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Male;Mohs Surgery;Ophthalmoscopy;Prothrombin Time;Trientine/ad [Administration & Dosage];Trientine/tu [Therapeutic Use];0 (Blood Proteins);789U1901C5 (Copper);AYI8EX34EU (Creatinine);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-1 (Aspartate Aminotransferases);EC 3-1-3-1 (Alkaline Phosphatase);SJ76Y07H5F (Trientine)","Brodland, D. G.;Bartley, G. B.",1992,Feb,,0,0,
210,"Penicillamine-associated myasthenia gravis, antiacetylcholine receptor and antistriational antibodies","Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody. Eleven cases of rheumatoid arthritis with penicillamine-associated antistriational antibodies have also been observed; in three of these cases there was evidence of myasthenia gravis. These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy.","Acetylcholine/me [Metabolism];Adult;Aged;*Antibodies;Arthritis, Rheumatoid/im [Immunology];Female;Humans;Immunoglobulin G;Male;Middle Aged;Muscles/im [Immunology];*Myasthenia Gravis/ci [Chemically Induced];Myasthenia Gravis/im [Immunology];*Penicillamine/ae [Adverse Effects];*Receptors, Cholinergic/im [Immunology];Thymectomy;0 (Antibodies);0 (Immunoglobulin G);0 (Receptors, Cholinergic);GNN1DV99GX (Penicillamine);N9YNS0M02X (Acetylcholine)","Masters, C. L.;Dawkins, R. L.;Zilko, P. J.;Simpson, J. A.;Leedman, R. J.",1977,Nov,,0,0,
211,Accumulation of manganese and copper in pallidum of cirrhotic patients: role in the pathogenesis of hepatic encephalopathy?,"Concentrations of zinc, copper and manganese were measured by atomic absorption spectrometry in samples of globus pallidus obtained at autopsy from 9 patients with chronic liver disease and an equal number of age-matched controls. Manganese concentrations were significantly increased several fold (p < 0.01) in globus pallidus of liver disease patients accompanied by smaller but significant 2-fold increases of copper. Zinc concentrations, on the other hand, were within normal limits. Increased pallidal manganese offers a cogent explanation for the observed T1-weighted MRI signal hyperintensity in pallidum of cirrhotic patients. Increased copper content in brain suggests the existence of common pathophysiologic mechanisms in inherited (Wilson Disease) and acquired hepatocerebral disorders.","Aged;*Copper/me [Metabolism];*Globus Pallidus/me [Metabolism];Globus Pallidus/pa [Pathology];*Hepatic Encephalopathy/me [Metabolism];Hepatic Encephalopathy/pa [Pathology];Humans;*Manganese/me [Metabolism];Middle Aged;Spectrophotometry, Atomic;42Z2K6ZL8P (Manganese);789U1901C5 (Copper)","Layrargues, G. P.;Shapcott, D.;Spahr, L.;Butterworth, R. F.",1995,Dec,,0,0,
212,Intractable neurological Wilson's disease treated with orthotopic liver transplantation,,Adult;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/su [Surgery];Humans;*Liver Transplantation;Male;Nervous System Diseases/et [Etiology];*Nervous System Diseases/su [Surgery];Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Mason, A. L.;Marsh, W.;Alpers, D. H.",1993,Sep,,0,0,
213,D-penicillamine in Wilson's disease presenting as acute liver failure with hemolysis,Wilson's disease in a young woman presenting with an acute course is described. The clinical manifestations were fulminant hepatic failure associated with marked intravascular hemolysis. Immediate D-penicillamine and high-dose steroid therapy did not influence the course of the disease. Necropsy revealed an increased hepatic copper content and cirrhosis with extensive necrosis of the liver.,Acute Disease;Adolescent;Ceruloplasmin/bl [Blood];Copper/an [Analysis];Copper/ur [Urine];Female;Glucocorticoids/tu [Therapeutic Use];*Hemolysis;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Diseases/di [Diagnosis];Liver Diseases/et [Etiology];Middle Aged;*Penicillamine/tu [Therapeutic Use];0 (Glucocorticoids);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Vielhauer, W.;Eckardt, V.;Holtermuller, K. H.;Luth, J. B.;Schulte, B.;Prellwitz, W.;Sonntag, W.",1982,Dec,,0,0,
214,Ion efflux systems involved in bacterial metal resistances,"Studying metal ion resistance gives us important insights into environmental processes and provides an understanding of basic living processes. This review concentrates on bacterial efflux systems for inorganic metal cations and anions, which have generally been found as resistance systems from bacteria isolated from metal-polluted environments. The protein products of the genes involved are sometimes prototypes of new families of proteins or of important new branches of known families. Sometimes, a group of related proteins (and presumedly the underlying physiological function) has still to be defined. For example, the efflux of the inorganic metal anion arsenite is mediated by a membrane protein which functions alone in Gram-positive bacteria, but which requires an additional ATPase subunit in some Gram-negative bacteria. Resistance to Cd2+ and Zn2+ in Gram-positive bacteria is the result of a P-type efflux ATPase which is related to the copper transport P-type ATPases of bacteria and humans (defective in the human hereditary diseases Menkes' syndrome and Wilson's disease). In contrast, resistance to Zn2+, Ni2+, Co2+ and Cd2+ in Gram-negative bacteria is based on the action of proton-cation antiporters, members of a newly-recognized protein family that has been implicated in diverse functions such as metal resistance/nodulation of legumes/cell division (therefore, the family is called RND). Another new protein family, named CDF for 'cation diffusion facilitator' has as prototype the protein CzcD, which is a regulatory component of a cobalt-zinc-cadmium resistance determinant in the Gram-negative bacterium Alcaligenes eutrophus. A family for the ChrA chromate resistance system in Gram-negative bacteria has still to be defined. [References: 102]","ATP-Binding Cassette Transporters/ph [Physiology];Adenosine Triphosphatases/ph [Physiology];Alcaligenes/ge [Genetics];Alcaligenes/me [Metabolism];Bacteria/ge [Genetics];*Bacteria/me [Metabolism];Drug Resistance, Microbial/ge [Genetics];Drug Resistance, Microbial/ph [Physiology];Escherichia coli/ge [Genetics];Escherichia coli/me [Metabolism];Ion Transport/ge [Genetics];Ion Transport/ph [Physiology];*Metals/pk [Pharmacokinetics];Staphylococcus/ge [Genetics];Staphylococcus/me [Metabolism];0 (Metals);EC 3-6-1 (Adenosine Triphosphatases)","Nies, D. H.;Silver, S.",1995,Feb,,0,0,
215,A copper-sulfur complex in the liver of a patient with Wilson's disease,"An asymptomatic 16-year-old boy was found to have Wilson's disease without Kayser-Fleischer rings. Liver biopsy showed chronic active hepatitis with 1025 micrograms copper/g dry weight. After 19 months of d-penicillamine therapy, the liver histology became almost normal and the copper content decreased to 238 micrograms/g dry weight. The liver specimens obtained before and after treatment were studied by X-ray probe microanalysis. After treatment, both copper and sulfur decreased in hepatocellular lysosomes. The estimated molar ratio of the decreased copper to the decreased sulfur was 32/100. These figures suggest that lysosomal copper exists in the form of metallothionein.","Adolescent;Biopsy;Calcium/me [Metabolism];*Copper/me [Metabolism];Electron Probe Microanalysis;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Inactivation, Metabolic;Iron/me [Metabolism];Lysosomes/me [Metabolism];Male;Penicillamine/tu [Therapeutic Use];Phosphorus/me [Metabolism];*Sulfur/me [Metabolism];27YLU75U4W (Phosphorus);70FD1KFU70 (Sulfur);789U1901C5 (Copper);E1UOL152H7 (Iron);GNN1DV99GX (Penicillamine);SY7Q814VUP (Calcium)","Sasa, A.;Hayashi, H.;Yagi, A.;Ohguchi, S.;Kidokoro, R.;Sato, Y.;Sakamoto, N.",1986,Dec,,0,0,
216,Fulminant hepatic failure during perinatal period in a pregnant woman with Wilson's disease,"Wilson's disease associated with hepatic failure is not common and the underlying mechanism triggering the event is not known at present. We treated a 28-year-old Japanese woman with Wilson's disease who developed hepatic failure associated with hemolytic crisis just after delivery. She was diagnosed as having Wilson's disease at 12 years of age, at which time she started taking D-penicillamine. She had previously delivered two children without difficulty. When she found out she was pregnant this time, she stopped taking D-penicillamine in contrast to taking it faithfully during her first two pregnancies. On the day of delivery of her full-term baby, jaundice developed accompanied with severe hemolytic crisis. Plasma exchanges and blood transfusion were performed and D-penicillamine administration was started again. She gradually recovered and apparently was following a good clinical course. However, on day 30 the second hemolytic crisis occurred and subsequent liver failure led her to death on day 50. At autopsy her liver was cirrhotic and showed massive necrosis. Prophylactic oral administration of D-penicillamine and careful observation are therefore recommended to prevent hemolytic crisis during the perinatal period.","Adult;Anemia, Hemolytic/et [Etiology];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver/pa [Pathology];*Liver Diseases/et [Etiology];Liver Diseases/pa [Pathology];Penicillamine/tu [Therapeutic Use];Pregnancy;*Puerperal Disorders/et [Etiology];Puerperal Disorders/pa [Pathology];GNN1DV99GX (Penicillamine)","Shimono, N.;Ishibashi, H.;Ikematsu, H.;Kudo, J.;Shirahama, M.;Inaba, S.;Maeda, K.;Yamasaki, K.;Niho, Y.",1991,Feb,,0,0,
217,Oral zinc sulphate as primary therapeutic intervention in a child with Wilson disease,"An 8-year-old boy with an hepatic form of Wilson disease was treated with oral zinc sulphate as the primary and sole therapy. After 4 months, liver function had dramatically improved, and the parameters characterizing copper metabolism had also normalized.","Administration, Oral;Child;Copper/ph [Physiology];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Sulfates/ad [Administration & Dosage];*Zinc/ad [Administration & Dosage];0 (Sulfates);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Milanino, R.;Marrella, M.;Moretti, U.;Velo, G. P.;Deganello, A.;Ribezzo, G.;Tato, L.",1989,Jun,,0,0,
218,Copper and liver disease,"There has been some limited progress in the understanding of the basic defect in Wilson disease and the gene concerned has been located to the chromosome region 13q14. Treatment with zinc has emerged as a definite alternative to penicillamine administration and some shortcomings and/or hazards of both forms of therapy have emerged as their modes of action have been studied more carefully. Tetrathimolybdate may have a place in treatment, especially when rapid complexing of copper is important. Hepatic copper accumulation occurs in a number of cholestatic diseases and they play an important part in pathogenesis and can occasionally lead to neurologic toxic effects. Copper overload in the newborn period when biliary excretion of copper is inefficient may establish a vicious cycle of copper accumulation and liver damage in Indian childhood cirrhosis and less frequently in babies in other countries. [References: 43]","Adult;Chelating Agents/tu [Therapeutic Use];Child;Cholestasis/et [Etiology];*Cholestasis/pp [Physiopathology];*Copper/ph [Physiology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Infant;Infant, Newborn;*Liver Diseases/dt [Drug Therapy];Liver Diseases/pp [Physiopathology];Molybdenum/tu [Therapeutic Use];*Penicillamine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Danks, D. M.",1991,Jan,,0,0,
219,Prognosis of Wilson's disease in childhood,"Wilson's disease in childhood has several characters distinct from those in adults. The progression of the disease tends to be rapid, hepatic manifestations are common, cerebral symptoms related to dystonia are predominant, and tremor is rare. Forty-nine children with Wilson's disease under the age of 15 were treated with D-penicillamine for 2 to 15 years. None of the presymptomatic patients subsequently developed any symptoms of the disease. The results of treatment in patients who had exhibited only hepatic symptoms were also excellent. However, neurological manifestations associated with a history of jaundice or ascites responded less well to chelation. These observations clearly indicate that early diagnosis and treatment are extremely important to ensure normal lives for children with Wilson's disease.","Adolescent;Age Factors;Ascites/co [Complications];Child;Child, Preschool;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatomegaly/co [Complications];Humans;Jaundice/co [Complications];Penicillamine/tu [Therapeutic Use];Prognosis;Splenomegaly/co [Complications];GNN1DV99GX (Penicillamine)","Arima, M.;Takeshita, K.;Yoshino, K.;Kitahara, T.;Suzuki, Y.",1977,Oct 12,,0,0,
220,Effects of long-term treatment in Wilson's disease with D-penicillamine and zinc sulphate,"The results of treatment with D-penicillamine (D-P) or zinc sulphate (Zn) in 67 newly diagnosed cases of Wilson's disease have been compared. All patients (7 with hepatic, 1 with psychiatric and 59 with neurological or preclinical forms) were fully compliant. During 12 years of observation, 34 patients received d-P and 33 Zn as the primary treatment. Fifteen patients (44%) discontinued D-P, in 10 cases owing to side effects. Four (12%) patients discontinued Zn, in 2 cases because of side-effects. One patient who received Zn deteriorated during the first few months after the initiation of therapy. The effectiveness of long-term treatment with D-P and Zn was similar in those patients who were able to continue the initial therapy. Zn was tolerated better than D-P; we suggest, therefore, that it may be recommended as an initial therapy for patients in the preclinical stage of Wilson's disease or with neurological presentation of the disease. More observation is needed for patients with the hepatic and psychiatric forms of the disease.",Adult;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Patient Compliance;*Penicillamine/tu [Therapeutic Use];Time Factors;Treatment Outcome;*Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine),"Czlonkowska, A.;Gajda, J.;Rodo, M.",1996,Mar,,1,1,
221,Wilson's disease with cerebral manifestation: monitoring therapy by CSF copper concentration,"The clinical courses, cerebrospinal fluid (CSF) and serum copper concentrations and urinary copper excretions under different schemes of drug treatment in four patients with cerebral manifestations of Wilson's disease were monitored over 6-11 years. CSF copper concentration measurements were performed from the beginning of therapy onwards in three patients and from 16 months after initial treatment onwards in the fourth. CSF copper levels decreased slowly over the years in parallel with clinical improvements, and increased in one patient who interrupted therapy for 2 years. These findings confirm our hypothesis that the concentration of copper in the CSF is a valuable quantitative parameter reflecting the normalization of copper in the brain. Copper measurements during phases of initial neurological deterioration in two patients receiving D-penicillamine, and in one patient receiving D-penicillamine and zinc sulphate, revealed decreased free serum copper and CSF copper levels.",Adult;*Brain/me [Metabolism];Ceruloplasmin/an [Analysis];Chelation Therapy/ae [Adverse Effects];*Chelation Therapy;Copper/an [Analysis];*Copper/cf [Cerebrospinal Fluid];Female;*Hepatolenticular Degeneration/cf [Cerebrospinal Fluid];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Humans;Male;Neurocognitive Disorders/et [Etiology];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];*Sulfates/tu [Therapeutic Use];*Zinc Compounds/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Hartard, C.;Weisner, B.;Dieu, C.;Kunze, K.",1993,Dec,,0,0,
222,Relationship between striatal glucose consumption and copper excretion in patients with Wilson's disease treated with D-penicillamine,"In 12 patients with Wilson's disease treated with D-penicillamine (DPA), the regional cerebral metabolic rate of glucose consumption of the lentiform and caudate nucleus was analysed using the 18Fluorodeoxyglucose method and correlated with the clinical symptoms of the patients, the ceruloplasmin level, the serum level of free copper and the 24-h copper excretion. The more copper was eliminated, the higher was the basal ganglia glucose consumption. On the other hand, in seven patients who had been treated for more than 7 years a significant decline of the basal ganglia glucose consumption was observed, suggesting too low a maintenance dose of DPA.","Adolescent;Adult;Ceruloplasmin/an [Analysis];*Copper/ur [Urine];Corpus Striatum/dg [Diagnostic Imaging];*Corpus Striatum/me [Metabolism];Deoxyglucose/aa [Analogs & Derivatives];Female;Fluorine Radioisotopes;Fluorodeoxyglucose F18;*Glucose/me [Metabolism];Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Middle Aged;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Tomography, Emission-Computed;0 (Fluorine Radioisotopes);0Z5B2CJX4D (Fluorodeoxyglucose F18);789U1901C5 (Copper);9G2MP84A8W (Deoxyglucose);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);IY9XDZ35W2 (Glucose)","Hefter, H.;Kuwert, T.;Herzog, H.;Arendt, G.;Stremmel, W.;Feinendegen, L. E.",1993,Nov,,0,0,
223,Dopamine D2 receptor binding and cerebral glucose metabolism recover after D-penicillamine-therapy in Wilson's disease,"Regional cerebral glucose metabolism (rCMRGlc) and dopamine D2 receptor binding were measured in a 31-year-old, severely affected, untreated patient with Wilson's disease of 3 years' duration using positron emission tomography and 18F-deoxyglucose and 18F-methylspiperone ([18F]MSP), respectively. There was a severe reduction of striatal and extrastriatal rCMRGlc as well as of striatal [18F]MSP accumulation rate. After 1 year of treatment with D-penicillamine, striatal and extrastriatal rCMRGlc and striatal [18F]MSP accumulation rate reached almost normal levels. It is hypothesized that recovery of motor functions due to copper trapping therapy was associated with an increase in basal ganglia activity and a re-expression or upregulation of dopamine D2 receptors.","Adult;Basal Ganglia/me [Metabolism];*Brain/me [Metabolism];Brain/pa [Pathology];Deoxyglucose;Dopamine Agents;Fluorine Radioisotopes;*Glucose/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Magnetic Resonance Imaging;Male;Neurons/me [Metabolism];*Penicillamine/tu [Therapeutic Use];*Receptors, Dopamine D2/me [Metabolism];Spiperone/aa [Analogs & Derivatives];Tomography, Emission-Computed;0 (Dopamine Agents);0 (Fluorine Radioisotopes);0 (Receptors, Dopamine D2);4X6E73CJ0Q (Spiperone);87539-19-3 (3-N-methylspiperone);9G2MP84A8W (Deoxyglucose);GNN1DV99GX (Penicillamine);IY9XDZ35W2 (Glucose)","Schlaug, G.;Hefter, H.;Nebeling, B.;Engelbrecht, V.;Weiss, P.;Stocklin, G.;Seitz, R. J.",1994,Oct,,0,0,
224,Induction of auto-immune syndromes by penicillamine therapy in rheumatoid arthritis and other diseases,,"*Arthritis, Rheumatoid/dt [Drug Therapy];*Autoimmune Diseases/ci [Chemically Induced];Captopril/im [Immunology];Cystinuria/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];Penicillamine/im [Immunology];Pyrithioxin/im [Immunology];9G64RSX1XD (Captopril);AK5Q5FZH2R (Pyrithioxin);GNN1DV99GX (Penicillamine)","Jaffe, I. A.",1981,,,0,0,
225,Cranial MRI in Wilson's disease,"Thirty-eight patients with biochemically proven Wilson's disease underwent magnetic resonance-imaging (MRI) of the brain as well as neurological examinations. The patients were scanned using spin-echo (SE) sequences; the neurologist was looking for typical symptoms: dysarthria, tremor, ataxia, rigidity/bradykinesia and chorea/dystonia. Pathological MR findings believed secondary to this uncommon inherited disorder of copper metabolism were found in twenty-two subjects. Focal abnormalities were seen in the lenticular, thalamic and caudate nuclei as well as in brain stem and white matter; these lesions were best demonstrated on T2-weighted sequences as hyperintense areas. In eight patients we found diffuse brain atrophy with consecutive widening of the ventricular system. Five subjects showed mild, nineteen severe neurologic deficits. Generally there was no correlation between MR findings and clinical neurological symptoms; the impairment of cell-metabolism causing functional alterations of the brain precedes morphological changes. During treatment with the copper chelator D-penicillamine there seemed to be a phased course of disease. Shortening of T1-relaxation due to paramagnetic influence of copper was not seen; a possible explanation could be intracellular deposition--a proton-electron-dipolar-dipolar-interaction would therefore be impossible.",Adult;Atrophy;*Brain/pa [Pathology];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pa [Pathology];Humans;*Magnetic Resonance Imaging;Male,"Prayer, L.;Wimberger, D.;Kramer, J.;Grimm, G.;Oder, W.;Imhof, H.",1990,,,0,0,
226,Wilson's disease: normalisation of cortically evoked motor responses with treatment,"A newly diagnosed patient with Wilson's disease is reported in whom the only clearly pathological neurophysiological findings before treatment were abnormal electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation. Serial examinations over 10 months following commencement of treatment with D-penicillamine revealed normalisation of EMG responses. Pathophysiologically, the initially abnormal EMG responses probably resulted from reversible impairment of impulse propagation along cortico-motor-neuronal pathways and/or a reduced excitability of cortical cells due to impaired function of the basal ganglia.","Adolescent;*Electromyography;Evoked Potentials, Auditory/ph [Physiology];Evoked Potentials, Somatosensory/ph [Physiology];Globus Pallidus/pa [Pathology];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration/th [Therapy];Humans;Magnetic Resonance Imaging;Magnetics;Male;Neural Conduction/ph [Physiology];*Penicillamine/tu [Therapeutic Use];Putamen/pa [Pathology];GNN1DV99GX (Penicillamine)","Meyer, B. U.;Britton, T. C.;Benecke, R.",1991,Sep,,0,0,
227,Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease,"Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and--to a lesser extent--cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment.","Adult;*Brain/dg [Diagnostic Imaging];Deoxyglucose/aa [Analogs & Derivatives];Female;Fluorine Radioisotopes;Fluorodeoxyglucose F18;*Glucose/me [Metabolism];*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];Tomography, Emission-Computed;0 (Fluorine Radioisotopes);0Z5B2CJX4D (Fluorodeoxyglucose F18);9G2MP84A8W (Deoxyglucose);GNN1DV99GX (Penicillamine);IY9XDZ35W2 (Glucose)","Kuwert, T.;Hefter, H.;Scholz, D.;Milz, M.;Weiss, P.;Arendt, G.;Herzog, H.;Loken, M.;Hennerici, M.;Feinendegen, L. E.",1992,,,0,0,
228,Evoked potentials in patients with non-neurological Wilson's disease,"In Wilson's disease neurological manifestations result from the damage in the basal ganglia, even if a widespread degeneration of the brain occurs. The few studies performed using evoked potentials with the aim of identifying subclinical dysfunction in the three major sensory pathways have never shown abnormalities in patients without neurological manifestations. To verify this observation we studied 12 patients suffering from Wilson's disease in a pre-neurological stage by using pattern visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) to median nerve stimulation and brainstem auditory evoked potentials (BAEPs). Four of these patients had not yet been treated with penicillamine or trientine (triethylenetetramine dihydrochloride), while the remaining 8 patients were on treatment for at least 1 year. In 3 patients of this second group and in 1 patient of the first group we observed a significant (3 SD over the mean) increase in P100 wave latency, while SEPs and BAEPs were found to be abnormal in only 1 patient, respectively.",Adolescent;Adult;Child;*Evoked Potentials;Female;*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Reaction Time,"Aiello, I.;Sau, G. F.;Cacciotto, R.;Puliga, M. V.;Lentinu, M. E.;Muzzu, S.;Posadinu, D.;Traccis, S.",1992,Feb,,0,0,
229,The influence of prolonged treatment with D-penicillamine on the immune response in Wilson's disease,"Humoral and cell-mediated immunity were studied in a group of patients with Wilson's disease not previously treated with D-penicillamine, and in a group of patients treated with the drug for more than two years. The previously untreated patients showed an exaggerated humoral immune response, i. e. increased levels of IgG and, IgM, higher titer of antibodies to Kunin's antigen, and depression of cell-mediated immunity, namely a decreased response to DNCB, decreased lymphocyte transformation after stimulation with Con A, PPD, Candida and streptokinase and a reduced response to streptokinase in the MIF test. After treatment the humoral response returned to normal, and in the case of IgA and antibodies to S. typhi O antigen, it even dropped below normal values. The cell-mediated immune response returned to normal with the exception of lymphocyte transformation by PHA and Candida albicans. In in vitro studies it was found that D-penicillamine had no influence on lymphocyte transformation when PHA and Con A were used as mitogens. With PPD as antigen, lymphocyte stimulation and migration inhibition were inhibited by concentrations of penicillamine ranging from 6 to 1000 microgram/ml.","Adult;Cell Migration Inhibition;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/im [Immunology];Humans;Immunity/de [Drug Effects];Immunity, Cellular/de [Drug Effects];Immunoglobulin A/an [Analysis];Immunoglobulin G/an [Analysis];Immunoglobulin M/an [Analysis];In Vitro Techniques;Leukocytes/de [Drug Effects];Lymphocyte Activation/de [Drug Effects];Male;Middle Aged;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Skin Tests;0 (Immunoglobulin A);0 (Immunoglobulin G);0 (Immunoglobulin M);GNN1DV99GX (Penicillamine)","Czlonkowska, A.",1977,Dec 02,,0,0,
230,[D-Penacillamine. From constituent of penicillins to significant drug],"D-Penicillamine is used against a variety of diseases. For many years it has been successful in treating Wilson's disease, cystinuria and heavy-metal poisonings. It also proved to be effective against rheumatoid arthritis, scleroderma, chronic active hepatitis, pulmonary fibrosis and multiple sclerosis. However, the use of D-penicillamine is still limited owing to the frequent occurrence of considerable, though generally reversible, side effects. This article deals with the history of D-penicillamine as well as the methods of its synthesis, its pharmacokinetics, effects and side effects. In addition, the significance of the stereo isomeric L-penicillamine is discussed.","Arthritis, Rheumatoid/dt [Drug Therapy];Cystinuria/dt [Drug Therapy];Hepatitis/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Multiple Sclerosis/dt [Drug Therapy];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];*Penicillins;Poisoning;Pulmonary Fibrosis/dt [Drug Therapy];Stereoisomerism;Structure-Activity Relationship;0 (Penicillins);GNN1DV99GX (Penicillamine)","Lodemann, E.",1979,Sep,,0,0,
231,Computer-based approach to chelation therapy: a theoretical study of some chelating agents for the selective removal of toxic metal ions from plasma,"COMICS is a computer programme for calculating equilibrium concentrations of metal complexes and reactive species in multi-metal-multi-ligand systems. Its usefulness for analysing metal ion equilibria in blood plasma has been improved by including albumin as a ligand. Using this model system the distribution and removal of copper(II) and zinc ions in histidinaemia, lead poisoning and Wilson's disease have been examined. The efficacy of TRIEN in removing excess copper(II) is shown. The use of specific tripeptides such as Gly-Gly-His methyl ester for the selective removal of copper(II) is suggested. A possible chemoprophylaxis of influenza based on complexation of zinc is discussed. Calculations confirm that thiosemicarbazones such as methisazone and 2-acetylpyridine thiosemicarbazone are effective competitors for heavy metal ions under physiological conditions.","Amino Acid Metabolism, Inborn Errors/dt [Drug Therapy];Chelating Agents/bl [Blood];*Chelating Agents/tu [Therapeutic Use];*Computers;Hepatolenticular Degeneration/dt [Drug Therapy];Lead Poisoning/dt [Drug Therapy];Ligands;*Metals/bl [Blood];Models, Biological;Peptides/tu [Therapeutic Use];Serum Albumin/me [Metabolism];Thiosemicarbazones/tu [Therapeutic Use];Virus Diseases/dt [Drug Therapy];0 (Chelating Agents);0 (Ligands);0 (Metals);0 (Peptides);0 (Serum Albumin);0 (Thiosemicarbazones)","Agarwal, R. P.;Perrin, D. D.",1976,Sep,,0,0,
232,An 18-year follow-up of a case of D-penicillamine-induced Elastosis perforans serpiginosa,"Elastosis perforans serpiginosa (EPS) is a rare complication of chronic therapy with a high-dose of D-penicillamine (1 g daily for more than 5 years), characterized by the elimination of abnormal elastic fibers from the upper dermis through the epidermis. D-penicillamine (DPA) is a heavy metal chelator primarily used for disorders such as cystinuria and Wilson disease. This therapy can lead to induction of EPS through a still unknown mechanism. We report the follow-up of a D-penicillamine-induced EPS in patient with Wilson disease, which prompted us to switch the therapy with trientine (another metal chelator). After 14 years the cutaneous lesions are still visible; therefore, we conclude that the DPA-induced cutaneous damage is irreversible.",Adult;Humans;Male;*Penicillamine/ae [Adverse Effects];Skin Diseases/ci [Chemically Induced];Skin Diseases/pa [Pathology];Skin Diseases/th [Therapy];GNN1DV99GX (Penicillamine);Elastosis perforans serpiginosa,"Carlesimo, M.;Narcisi, A.;Cortesi, G.;Mari, E.;Fidanza, L.;De Marco, G.;Rossi, A.;Camplone, G.",2011,Jan-Mar,https://dx.doi.org/10.1177/039463201102400133,0,0,
233,"Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities","Wilson's disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson's disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes.","Adult;*Antirheumatic Agents/ae [Adverse Effects];*Anxiety/co [Complications];*Anxiety/px [Psychology];*Astringents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/px [Psychology];Humans;*Lichenoid Eruptions/ci [Chemically Induced];*Lichenoid Eruptions/dt [Drug Therapy];*Liver Diseases/co [Complications];Liver Function Tests;*Penicillamine/ae [Adverse Effects];Tomography, Emission-Computed, Single-Photon;*Zinc Acetate/tu [Therapeutic Use];0 (Antirheumatic Agents);0 (Astringents);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine)","Leggio, L.;Ferrulli, A.;Mirijello, A.;Abenavoli, L.;Di Giuda, D.;Funiciello, S.;Rotoli, M.;Gasbarrini, G.;Addolorato, G.",2007,Jan-Mar,https://dx.doi.org/10.1177/039463200702000122,0,0,
234,The bane of a silent illness: when Wilson's disease takes its course,"We present the case of a 21-year-old young lady with Wilson's disease, asymptomatic at first and consequently declining prophylaxis with chelating agents, who presented years after her diagnosis was made with multiple motor and neuropsychiatric manifestations of the disease, causing extensive morbidity and a major decrease in her quality of life. Following extensive education and supportive therapy, she showed conviction in the need for therapy. On close follow-up she continues to show compliance with appointments, the prescribed chelating agents, and psychotropic medication.",Adult;*Chelating Agents/tu [Therapeutic Use];*Cognitive Therapy;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;*Patient Compliance;Patient Education as Topic;Piperazines/tu [Therapeutic Use];Quality of Life;Thiazoles/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc Oxide/tu [Therapeutic Use];0 (Chelating Agents);0 (Piperazines);0 (Thiazoles);6UKA5VEJ6X (ziprasidone);SJ76Y07H5F (Trientine);SOI2LOH54Z (Zinc Oxide),"Chahine, L. M.;Chemali, Z. N.",2006,,https://dx.doi.org/10.2190/1A0B-2M98-0VVE-485R,0,0,
235,"Wilson's disease: clinical, genetic and pharmacological findings","Wilson's disease (WD) is an autosomal recessive disorder characterized by copper accumulation and toxicity in the liver and in other tissues. WD presents with liver disease, neurological or psychiatric disturbances or other less common clinical features. Diagnosis of WD is often difficult and may be formulated through clinical, biochemical, imaging, histochemical and genetic evaluations. Pharmacological approach in WD consists in copper chelating agents such as D-penicillamine, trientine, dimercaprol and tetrathiomolybdate. In 1997 zinc was approved for maintenance therapy of WD by the U.S. FDA. Orthotopic Liver Transplantation is indicated in fulminant hepatic failure, progressive hepatic insufficiency despite therapy, cirrhosis with complications of portal hypertension. However the most appropriate therapy, including OLT, remains controversial in WD and further studies are needed especially in order to differentiate the possibility of specific therapies for different WD phenotypes. [References: 38]",Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dh [Diet Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver Diseases/et [Etiology];0 (Chelating Agents);789U1901C5 (Copper),"Leggio, L.;Addolorato, G.;Abenavoli, L.;Gasbarrini, G.",2005,Jan-Mar,https://dx.doi.org/10.1177/039463200501800102,0,0,
236,Depression in hepatolenticular degeneration (Wilson's disease),"OBJECTIVE: To describe the course of depression in a patient with hepatolenticular degeneration (Wilson's disease). CLINICAL PICTURE: A 21-year-old male with hepatolenticular degeneration is described in whom depression was the earliest manifestation. Insomnia and psychomotor slowing were prominent. TREATMENT: The mood disturbance showed limited response to tricyclic antidepressants, mianserin, lithium augmentation and initial decoppering therapy. Introduction of the chelating agent tetrathiomolybdate was followed by normalisation of mood and improvement in non-psychiatric symptoms. OUTCOME: Three years after the disorder was first diagnosed the patient was euthymic and fully functional. CONCLUSIONS: Although hepatolenticular degeneration is rare, it commonly presents with psychiatric symptoms. It is important for psychiatrists to be aware of the condition and its psychiatric manifestations.","Adult;Antidepressive Agents, Tricyclic/tu [Therapeutic Use];Chelating Agents/tu [Therapeutic Use];Comorbidity;*Depressive Disorder/di [Diagnosis];Depressive Disorder/dt [Drug Therapy];Depressive Disorder/ep [Epidemiology];Drug Therapy, Combination;Follow-Up Studies;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ep [Epidemiology];*Hepatolenticular Degeneration/px [Psychology];Humans;Male;Mianserin/tu [Therapeutic Use];Molybdenum/tu [Therapeutic Use];Psychomotor Disorders/di [Diagnosis];Psychomotor Disorders/ep [Epidemiology];Sleep Initiation and Maintenance Disorders/di [Diagnosis];Sleep Initiation and Maintenance Disorders/ep [Epidemiology];0 (Antidepressive Agents, Tricyclic);0 (Chelating Agents);250PJI13LM (Mianserin);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Walter, G.;Lyndon, B.",1997,Dec,https://dx.doi.org/10.3109/00048679709065517,0,0,
237,Zinc acetate treatment in Wilson's disease,"OBJECTIVE: To briefly review the pathophysiology and diagnosis of Wilson's disease, and to evaluate the pharmacology, pharmacokinetics, clinical utility, adverse effects, dosing regimens, and pharmacoeconomics of zinc acetate therapy in Wilson's disease. DATA SOURCES: A MEDLINE search (December 1966-December 1996) of the English-language literature using the terms zinc and Wilson's disease was conducted to identify pertinent clinical trials, review articles, and case reports. Additional articles were selected from bibliographies of the reviewed literature. STUDY SELECTION AND DATA EXTRACTION: Due to the rarity of the disease, all articles were considered for possible inclusion in this review. Single case reports are referenced, but were not selected for evaluation. DATA SYNTHESIS: Wilson's disease, an inherited disorder of copper metabolism, is fatal if untreated. The chelating drugs penicillamine and trientine have been the mainstay of therapy; however, adverse reactions of chelators often interfere with successful treatment. Recently, zinc acetate was approved in the US for maintenance therapy in patients initially treated with a chelating agent. Although studies evaluating large populations are lacking zinc therapy has demonstrated exceptional safety and efficacy over a period of 40 years. Zinc acetate can be used during pregnancy and for the treatment of presymptomatic patients, although data do not support its use as monotherapy in patients with acute neurologic or hepatic disease. CONCLUSIONS: Zinc acetate is an effective maintenance therapy for patients with Wilson's disease. Negligible toxicity, compared with that of previously approved treatments, is a major advantage. [References: 57]",Age Factors;Clinical Trials as Topic;Copper/ai [Antagonists & Inhibitors];Copper/me [Metabolism];Drug Administration Schedule;Drug Interactions;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Lactation;Pregnancy;Zinc Acetate/ae [Adverse Effects];Zinc Acetate/pk [Pharmacokinetics];Zinc Acetate/pd [Pharmacology];*Zinc Acetate/tu [Therapeutic Use];789U1901C5 (Copper);FM5526K07A (Zinc Acetate),"Anderson, L. A.;Hakojarvi, S. L.;Boudreaux, S. K.",1998,Jan,https://dx.doi.org/10.1345/aph.17075,0,0,
238,Wilson's disease in childhood. Variability of clinical presentation,"Although Wilson's Disease is a treatable disorder, 9 of 15 cases referred with undiagnosed liver disease in the present series died in 3 to 53 days of admission. We have reviewed these cases to identify features that would allow earlier diagnosis and improvement in management. The presenting symptoms were lethargy and malaise (11 cases), jaundice (11), abdominal pain (9), and deteriorating school performance (4). At diagnosis, all fatal cases had jaundice and ascites, while only one of the 6 survivors had ascites and two had jaundice. Evidence of hemolysis was found in 3 fatal cases and 5 survivors. Serum bilirubin concentrations, aspartate transaminase, and prolongation of prothrombin time were significantly more abnormal in the fatal cases (p less than 0.01) as compared with the survivors. Cirrhosis was present in all fatal cases and in 2 of the 6 survivors. Wilson's Disease must be excluded in children presenting with frank liver disease as well as those with hemolytic anemia, persisting lethargy, abdominal pain, or deteriorating school performance.",Adolescent;Aspartate Aminotransferases/bl [Blood];Bilirubin/bl [Blood];Child;Female;Hemolysis;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Immunoglobulins/me [Metabolism];Jaundice/co [Complications];Male;Penicillamine/ad [Administration & Dosage];0 (Immunoglobulins);EC 2-6-1-1 (Aspartate Aminotransferases);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin),"Nazer, H.;Ede, R. J.;Mowat, A. P.;Williams, R.",1983,Nov,https://dx.doi.org/10.1177/000992288302201104,0,0,
239,Unusual problems tend to appear in crops,,"Adult;Biopsy;Ceruloplasmin/bl [Blood];Child;Diagnosis, Differential;Diet;Dimercaprol/tu [Therapeutic Use];Eye Manifestations;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Hypophosphatemia, Familial/di [Diagnosis];Male;Neurologic Manifestations;Penicillamine/tu [Therapeutic Use];0CPP32S55X (Dimercaprol);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Gharib, M.",1971,Oct,https://dx.doi.org/10.1177/000992287101001023,0,0,
240,Factors modifying the prognosis of Wilson's disease in childhood,"The prognosis of Wilson's disease was investigated in 96 patients, in whom the disease had presented before 15 years of age and had begun between 1965 and 1983 (when D-penicillamine was widely available in Japan). In the activities of daily living, the prognosis was poor in those patients presenting with neurological symptoms. Interruption of D-penicillamine treatment was seen in one third of the patients, and it worsened the prognosis. Toxic side effects were seen in about half of the patients, being more frequent in the patients with initial neurological symptoms. A disappointing 17% of patients with slight or no side effects discontinued the drug. Death occurred in eight patients of whom seven had had initial hepatic symptoms. Not only early diagnosis and treatment before the appearance of hepatic failure or neurological symptoms, but also treatment throughout life without interruption is important for improving the prognosis of Wilson's disease.",Adolescent;Child;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];Prognosis;GNN1DV99GX (Penicillamine),"Kudo, H.;Arima, M.",1987,Jan,https://dx.doi.org/10.1177/088307388700200111,0,0,
241,Recognition and treatment of neurologic Wilson's disease,"As Wilson's disease is both preventable and treatable, the diagnosis must not be missed. Despite this, it is usually misdiagnosed. Misdiagnosis and delay in treatment are clinically relevant because if left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability, and death. Those adequately treated have a normal life span. Wilson's disease is an autosomal recessive disease caused by mutations in the ATP7B gene. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. The clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, parkinsonism, ataxia, and choreoathetosis. Once the possibility of Wilson's disease is considered, diagnosis is straight forward. Currently available treatments, including zinc acetate and trientine, are generally well tolerated and effective. Copyright Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.",Ataxia/co [Complications];Ataxia/di [Diagnosis];Dysarthria/co [Complications];Dysarthria/ge [Genetics];Dysarthria/me [Metabolism];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Liver/me [Metabolism];Male;Mutation/ge [Genetics];Treatment Outcome;*Trientine/tu [Therapeutic Use];Young Adult;*Zinc Acetate/tu [Therapeutic Use];FM5526K07A (Zinc Acetate);SJ76Y07H5F (Trientine),"Lorincz, M. T.",2012,Nov,https://dx.doi.org/10.1055/s-0033-1334476,0,0,
242,Wilson disease in 71 patients followed for over two decades in a tertiary center in Saudi Arabia: a retrospective review,"BACKGROUND AND OBJECTIVES: Wilson disease (WD) is a rare autosomal recessive disease. Our objective was to describe the diverse patterns, therapies, and outcomes of this disease. DESIGN AND SETTING: A retrospective study over two decades on WD patients in a tertiary care center in Saudi Arabia. PATIENTS AND METHODS: Clinical and laboratory findings of 71 patients with WD were retrieved from their charts, referral notes and our hospital electronic records and were analyzed. RESULTS: The mean age and standard deviation was 16.8 (10.7) years and 56.5% were males. The main manifestations of WD were hepatic, neurological, and mixed in 39 (54.9%), 12 (16.9%), and 20 (28.2%) patients, respectively, and 11 (15.5%) were asymptomatic cases detected by family screening. A family history of WD was positive in 41 (57.7%) patients, and consanguinity of parents was found in 26 (36.6%) patients. The mean (SD) follow-up period was 92.2 (72.9) (range, 1-320) months. Ten (14.1%) patients died during follow up, while 45 (63.4%) and 16 (22.5%) were still on or lost from follow-up, respectively. The mean (SD) age at the end of follow-up was 25.3 (12) (range, 4-62) years. Hepatoma was discovered in 5 (7.0%) patients. Penicillamine therapy was used by 58 (81.7%) patients, while zinc and trientine were given to 32 (45.1%) and 11 (15.5%) patients, respectively. Sixteen (22.5%) patients underwent liver transplantation and one died (1.4%) on the waiting list. The liver condition remained stable or improved in 35 (49.3%), and the neurological status showed improvement in 11 (34.4%) of the 32 patients who had neurological involvement. CONCLUSIONS: This is the biggest cohort to be reported from the Middle East. WD presentation and outcome of WD are very diverse, and its diagnosis still depends on clinical, laboratory, and radiological evidence of abnormal copper metabolism. WD should be considered in patients of any age with obscure hepatic and/or neurological abnormalities.","Adolescent;Adult;*Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Disease Progression;Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/th [Therapy];Humans;Liver Function Tests;*Liver Transplantation;Male;Middle Aged;Prevalence;Retrospective Studies;Saudi Arabia/ep [Epidemiology];*Tertiary Care Centers;Time Factors;Young Adult;0 (Chelating Agents)","Al Fadda, M.;Al Quaiz, M.;Al Ashgar, H.;Al Kahtani, K.;Helmy, A.;Al Benmousa, A.;Abdulla, M.;Peedikayil, M.",2012,Nov-Dec,https://dx.doi.org/10.5144/0256-4947.2012.623,0,1,
243,Is blinking of the eyes affected in extrapyramidal disorders? An interesting observation in a patient with Wilson disease,"Blinking of eye is a routine human activity which seldom attracts any attention of clinicians in health and disease. There is experimental evidence that blink rate is affected in extrapyramidal disorders affecting the balance of these neurotransmitters. However, no observations regarding blink rate in Wilson disease (WD) have been reported previously. We report a patient of WD with an increased spontaneous blink rate. A 24-year-old lady presented complaining of tremulousness of both upper limbs and head for 2 years, dysphagia and difficulty in speaking for 1.5 years and abnormal behaviour for last 1 year. We observed that her blink rate at rest was 32/min. Serum ceruloplasmin level was low (0.08 g/l). The patient was started on therapy with D-penicillamine, zinc sulphate, levodopa-carbidopa and trihexiphenidyl. At 1-month follow-up, patient's tremors were markedly decreased and blink rate at rest was decreased to 12/min.","Adult;Antiparkinson Agents/tu [Therapeutic Use];*Basal Ganglia Diseases/di [Diagnosis];Basal Ganglia Diseases/dt [Drug Therapy];Basal Ganglia Diseases/pp [Physiopathology];Blinking/de [Drug Effects];Blinking/ph [Physiology];*Blinking;Carbidopa/tu [Therapeutic Use];Ceruloplasmin/an [Analysis];Drug Therapy, Combination;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Levodopa/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Trihexyphenidyl/tu [Therapeutic Use];Zinc Sulfate/tu [Therapeutic Use];0 (Antiparkinson Agents);46627O600J (Levodopa);6RC5V8B7PO (Trihexyphenidyl);7733-02-0 (Zinc Sulfate);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);MNX7R8C5VO (Carbidopa)","Verma, R.;Lalla, R.;Patil, T. B.",2012,Nov 27,https://dx.doi.org/10.1136/bcr-2012-007367,0,0,
244,Response to different therapeutic approaches in Wilson disease. A long-term follow up study,"BACKGROUND AND AIMS: There are certain areas of uncertainty regarding the best therapeutic approach in patients diagnosed with Wilson Disease (WD). Our aim was to assess treatment response to different therapies in a cohort of WD patients followed in a single center. MATERIAL AND METHODS: This is an observational, descriptive study in which clinical, laboratory and imaging data are reviewed in a series of 20 WD patients with a median follow-up of 14 years. Type of presentation, treatment used, biochemical and copper homeostasis parameters were elicited. RESULTS: Median age at diagnosis was 22 years. The most frequent form of presentation was hepatic (n = 10, 50%; mean age: 21.5 years), followed by neurological (25%; mean age: 34.5 years) and mixed (15%). The initial treatment in both symptomatic and asymptomatic patients at diagnosis was d-penicillamine in 90% and Zinc (Zn) in 10%, respectively. Patients who were maintained on d-penicillamine for the whole period had complete biochemical normalization (baseline ALT: 220 IU/l; last follow up 38 IU/l). In contrast, patients in whom d-penicillamine was switched to Zn, irrespective of the cause, did not show a complete biochemical remission (baseline ALT: 100 IU/l vs. 66 IU/l at last follow-up). CONCLUSIONS: Treatment was found to be effective in most cases regardless of the drug used. However, side effects were common in those treated with d-penicillamine agents, and required switching to zinc. Therapy with zinc was well tolerated and appeared to have a good efficacy. However, in 33%, a complete normalization of liver enzymes was never reached.",Adolescent;Adult;Biomarkers/bl [Blood];Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];Child;*Copper/bl [Blood];Drug Substitution;Female;Follow-Up Studies;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Retrospective Studies;Spain;Time Factors;Treatment Outcome;Young Adult;Zinc/ae [Adverse Effects];*Zinc/tu [Therapeutic Use];0 (Biomarkers);0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Rodriguez, B.;Burguera, J.;Berenguer, M.",2012,Nov-Dec,,1,1,
245,"Concurrent massive breast enlargement, myasthenia gravis and dermopathy as manifestations of penicillamine toxicity in a Wilson's disease patient","Penicillamine toxicity in Wilson's disease has been well reported but rarely seen now as newer agents are being used. We present a case who developed multiple rare complications of Penicillamine concurrently. Our patient is one of three siblings on Penicillamine, she was the only one who developed massive breast enlargement four months after commencing Penicillamine therapy, as well as dermatological adverse reactions and myasthenia gravis three more months later. All the adverse effects improved soon after substitution of the offending agent with Trientine.",Adolescent;Breast/de [Drug Effects];*Breast/pa [Pathology];*Chelating Agents/ae [Adverse Effects];*Drug Eruptions/et [Etiology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Myasthenia Gravis/ci [Chemically Induced];Organ Size;*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Tan, S. S.;Latif, S. A.;Poh, W. Y.",2012,Jun,,0,0,
246,A novel long-range enhancer regulates postnatal expression of Zeb2: implications for Mowat-Wilson syndrome phenotypes,"The zinc-finger, E-box-binding homeobox-2 (Zeb2) gene encodes a SMAD-interacting transcription factor that has diverse roles in development and disease. Mutations at the hZeb2 locus cause Mowat-Wilson syndrome (MWS), a genetic disorder that is associated with mental retardation and other, case- and sex-dependent clinical features. Recent studies have detailed microRNA-mediated control of Zeb2, but little is known about the genomic context of this gene or of enhancer sequences that may direct its diverse functions. Here, we describe a novel transgenic rodent model in which Zeb2 regulatory sequence has been disrupted, resulting in a postnatal developmental phenotype that is autosomal dominant. The phenotype exhibits a genotype-by-sex interaction and manifests primarily as an acute attenuation of postnatal kidney development in males. Other aspects of embryonic and neonatal development, including neuronal, are unaffected. The transgene insertion site is associated with a 12 kb deletion, 1.2 Mb upstream of Zeb2, within a 4.1 Mb gene desert. A conserved sequence, derived from the deleted region, enhanced Zeb2 promoter activity in transcription assays. Tissue and temporal restriction of this enhancer activity may involve postnatal changes in proteins that bind this sequence. A control human/mouse VISTA enhancer (62 kb upstream of Zeb2) also up-regulated the Zeb2 promoter, providing evidence of a string of conserved distal enhancers. The phenotype arising from deletion of one copy of the extreme long-range enhancer indicates a critical role for this enhancer at one developmental stage. Haploinsufficiency of Zeb2 in this developmental context reflects inheritance of MWS and may underlie some sex-dependent, non-neural characteristics of this human inherited disorder.","Animals;Conserved Sequence/ge [Genetics];*Enhancer Elements, Genetic;Facies;Female;Gene Deletion;Gene Expression Profiling;*Gene Expression Regulation, Developmental;Genetic Loci;Genotype;Hirschsprung Disease/ge [Genetics];Hirschsprung Disease/pa [Pathology];*Homeodomain Proteins/ge [Genetics];Homeodomain Proteins/me [Metabolism];Humans;Intellectual Disability/ge [Genetics];Intellectual Disability/pa [Pathology];Kidney/em [Embryology];Kidney/gd [Growth & Development];Male;Mice;Microcephaly/ge [Genetics];Microcephaly/pa [Pathology];NIH 3T3 Cells;*Phenotype;Protein Binding;Rats;Rats, Sprague-Dawley;Rats, Transgenic;*Repressor Proteins/ge [Genetics];Repressor Proteins/me [Metabolism];Transcription Factors/ge [Genetics];Transcription Factors/me [Metabolism];Transgenes;Up-Regulation;0 (Homeodomain Proteins);0 (Repressor Proteins);0 (Transcription Factors);0 (ZEB2 protein, human);Mowat-Wilson syndrome","El-Kasti, M. M.;Wells, T.;Carter, D. A.",2012,Dec 15,https://dx.doi.org/10.1093/hmg/dds389,0,0,
247,Copper imbalances in ruminants and humans: unexpected common ground,"Ruminants are more vulnerable to copper deficiency than humans because rumen sulfide generation lowers copper availability from forage, increasing the risk of conditions such as swayback in lambs. Molybdenum-rich pastures promote thiomolybdate (TM) synthesis and formation of unabsorbable Cu-TM complexes, turning risk to clinical reality (hypocuprosis). Selection pressures created ruminant species with tolerance of deficiency but vulnerability to copper toxicity in alien environments, such as specific pathogen-free units. By contrast, cases of copper imbalance in humans seemed confined to rare genetic aberrations of copper metabolism. Recent descriptions of human swayback and the exploratory use of TM for the treatment of Wilson's disease, tumor growth, inflammatory diseases, and Alzheimer's disease have created unexpected common ground. The incidence of pre-hemolytic copper poisoning in specific pathogen-free lambs was reduced by an infection with Mycobacterium avium that left them more responsive to treatment with TM but vulnerable to long-term copper depletion. Copper requirements in ruminants and humans may need an extra allowance for the ""copper cost"" of immunity to infection. Residual cuproenzyme inhibition in TM-treated lambs and anomalies in plasma copper composition that appeared to depend on liver copper status raise this question ""can chelating capacity be harnessed without inducing copper-deficiency in ruminants or humans?"" A model of equilibria between exogenous (TM) and endogenous chelators (e.g., albumin, metallothionein) is used to predict risk of exposure and hypocuprosis; although risk of natural exposure in humans is remote, vulnerability to TM-induced copper deficiency may be high. Biomarkers of TM impact are needed, and copper chaperones for inhibited cuproenzymes are prime candidates.",Alzheimer Disease/dt [Drug Therapy];Animals;Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];*Chelating Agents;Copper/df [Deficiency];Copper/im [Immunology];Copper/me [Metabolism];*Copper;*Deficiency Diseases/ci [Chemically Induced];Deficiency Diseases/im [Immunology];Enzyme Inhibitors/ae [Adverse Effects];Enzyme Inhibitors/tu [Therapeutic Use];*Enzyme Inhibitors;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infection/im [Immunology];*Infection/me [Metabolism];Inflammation/dt [Drug Therapy];Molybdenum/ae [Adverse Effects];Molybdenum/tu [Therapeutic Use];*Molybdenum;Neoplasms/dt [Drug Therapy];*Nutritional Requirements;Ruminants;0 (Chelating Agents);0 (Enzyme Inhibitors);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Suttle, N. F.",2012,Sep 01,https://dx.doi.org/10.3945/an.112.002220,0,0,
248,A copper for your thoughts,,"Adult;*Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];Copper/po [Poisoning];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Insurance, Life;Penicillamine/tu [Therapeutic Use];*Trace Elements/me [Metabolism];Trace Elements/po [Poisoning];Trientine/tu [Therapeutic Use];Zinc Acetate/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);789U1901C5 (Copper);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Coates, R. A.",2012,,,0,0,
249,Kayser-Fleischer ring in Wilson's disease: a cohort study,"AIMS: To evaluate Wilson's disease (WD) features in Sardinian patients with Kayser-Fleischer (KF) ring and to evaluate correlations between modifications in KF and anti-copper therapy and systemic WD evolution. PATIENTS AND METHODS: Sixty-seven WD patients (35 m/32 f; mean age 41 years) were retrospectively studied. At diagnosis and during follow up comprehensive ophthalmologic and neurologic examinations, brain RMN and ECD SPECT, detailed objective laboratory studies and hepatic histological examination were performed on all patients for analysis. All patients were given anti-copper therapy with d-Penicillamine in mono-therapy or in combination with Zinc Salts. RESULTS: At diagnosis, KF was observed in 27% of patients with equal distribution in all age groups. Significant correlations between KF at diagnosis, neuro-psychiatric manifestations and pathologic features in brain RMN and in brain ECD SPECT were found at diagnosis. During follow up, a decrease in, or regression of KF was seen in 14% of patients. Anti-copper therapy leads to KF regression and prevents the appearance of KF. No significant correlations were observed between KF regression and clinical neurological or neuro-imaging improvement nor between KF modifications and clinical hepatic improvement. CONCLUSIONS: Our study highlights the peculiar features of Sardinian WD patients: low representation of KF, its equal distribution in all age groups, significant correlation between KF at diagnosis and clinical neurological manifestations, pathologic brain RMN and brain ECD-SPECT are highlighted by our study. Anti-copper therapy induces KF regression and prevents its onset. Therefore, KF ring does appear to be a predictive factor in the neurological and hepatic evolution of WD. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.","Adolescent;Adult;Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Cohort Studies;Disease Progression;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Italy;*Limbus Corneae/pa [Pathology];Liver/pa [Pathology];Magnetic Resonance Imaging;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Retrospective Studies;Tomography, Emission-Computed, Single-Photon;Treatment Outcome;0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Fenu, M.;Liggi, M.;Demelia, E.;Sorbello, O.;Civolani, A.;Demelia, L.",2012,Sep,https://dx.doi.org/10.1016/j.ejim.2012.04.005,0,0,
250,D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis,"D-Penicillamine (3,3-dimethyl-D-cysteine; DP) is an FDA-approved redox-active D-cysteine-derivative with antioxidant, disulfide-reducing, and metal chelating properties used therapeutically for the control of copper-related pathology in Wilson's disease and reductive cystine-solubilization in cystinuria. Based on the established sensitivity of metastatic melanoma cells to pharmacological modulation of cellular oxidative stress, we tested feasibility of using DP for chemotherapeutic intervention targeting human A375 melanoma cells in vitro and in vivo. DP treatment induced caspase-dependent cell death in cultured human metastatic melanoma cells (A375, G361) without compromising viability of primary epidermal melanocytes, an effect not observed with the thiol-antioxidants N-acetyl-L-cysteine (NAC) and dithiothreitol. Focused gene expression array analysis followed by immunoblot detection revealed that DP rapidly activates the cytotoxic unfolded protein response (UPR; involving phospho-PERK, phospho-eIF2alpha, Grp78, CHOP, and Hsp70) and the mitochondrial pathway of apoptosis with p53 upregulation and modulation of Bcl-2 family members (involving Noxa, Mcl-1, and Bcl-2). DP (but not NAC) induced oxidative stress with early impairment of glutathione homeostasis and mitochondrial transmembrane potential. SiRNA-based antagonism of PMAIP1 expression blocked DP-induced upregulation of the proapoptotic BH3-only effector Noxa and prevented downregulation of the Noxa-antagonist Mcl-1, rescuing melanoma cells from DP-induced apoptosis. Intraperitoneal administration of DP displayed significant antimelanoma activity in a murine A375 xenograft model. It remains to be seen if melanoma cell-directed induction of UPR and apoptosis using DP or improved DP-derivatives can be harnessed for future chemotherapeutic intervention.","Animals;Apoptosis/de [Drug Effects];Apoptosis Regulatory Proteins/pd [Pharmacology];Cell Line, Tumor;Humans;*Melanoma/dt [Drug Therapy];Melanoma/pa [Pathology];Mice;Mitochondria/de [Drug Effects];Neoplasm Transplantation;Oxidative Stress/de [Drug Effects];*Penicillamine/pd [Pharmacology];Proto-Oncogene Proteins c-bcl-2/bi [Biosynthesis];*Proto-Oncogene Proteins c-bcl-2/ph [Physiology];Transcriptome;Transplantation, Heterologous;*Unfolded Protein Response/de [Drug Effects];0 (Apoptosis Regulatory Proteins);0 (PMAIP1 protein, human);0 (Proto-Oncogene Proteins c-bcl-2);GNN1DV99GX (Penicillamine)","Qiao, S.;Cabello, C. M.;Lamore, S. D.;Lesson, J. L.;Wondrak, G. T.",2012,Oct,https://dx.doi.org/10.1007/s10495-012-0746-x,0,0,
251,Resolution of cranial MRI and SPECT abnormalities in a patient with Wilson's disease following oral zinc monotherapy,"A 38-year-old woman with Wilson's disease developed neurological deterioration after 25 years of low-dose penicillamine administration. She showed an akinetic-rigid syndrome and cerebellar motor ataxia. Brain MRI showed increased signal intensity at the bilateral pons, midbrain, putamen, and thalamus. 123I-IMP-SPECT revealed a diffuse reduction of cerebral blood flow at the bilateral cerebral hemisphere including the basal ganglia. After the patient's regimen was changed to zinc therapy, her neurological condition gradually improved, and she showed almost complete recovery within two years. Serial MRI and SPECT studies showed a marked improvement in the lesions.","Adult;Brain/dg [Diagnostic Imaging];*Brain/pa [Pathology];Cerebellar Ataxia/dg [Diagnostic Imaging];Cerebellar Ataxia/dt [Drug Therapy];Cerebellar Ataxia/pa [Pathology];Cerebrovascular Circulation;Female;Hepatolenticular Degeneration/dg [Diagnostic Imaging];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Iofetamine;Magnetic Resonance Imaging;Penicillamine/ae [Adverse Effects];Radiopharmaceuticals;Tomography, Emission-Computed, Single-Photon;*Zinc Acetate/tu [Therapeutic Use];0 (Radiopharmaceuticals);C2A5X08042 (Iofetamine);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine)","Ishida, S.;Doi, Y.;Yamane, K.;Sugino, M.;Kimura, F.;Hanafusa, T.;Fukui, H.;Tamai, H.",2012,,,0,0,
252,Endocrine symptoms as the initial manifestation of Wilson's disease,"Wilson's disease is a rare genetic disorder of copper metabolism. The difference in copper tissue accumulation is responsible for the various clinical manifestations of this disorder. If left untreated, Wilson's disease progresses to hepatic failure, severe neurological disability, and even death. Due to the complex clinical picture of Wilson's disease, its diagnosis relies on a high index of suspicion. In our paper, we present endocrine symptoms suggesting the presence of insulinoma and hyperprolactinemia as the initial clinical manifestation of Wilson's disease in a young female. Zinc acetate treatment resulted in the disappearance of hypoglycemia, galactorrhea, and menstrual abnormalities.","Amenorrhea/di [Diagnosis];Amenorrhea/et [Etiology];Diagnosis, Differential;Endocrine System/de [Drug Effects];Endocrine System/me [Metabolism];Endocrine System/pa [Pathology];Female;Galactorrhea/di [Diagnosis];Galactorrhea/et [Etiology];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Hyperprolactinemia/di [Diagnosis];Hyperprolactinemia/et [Etiology];*Insulinoma/di [Diagnosis];Insulinoma/et [Etiology];*Pancreatic Neoplasms/di [Diagnosis];Pancreatic Neoplasms/et [Etiology];Treatment Outcome;Young Adult;Zinc Acetate/tu [Therapeutic Use];FM5526K07A (Zinc Acetate)","Krysiak, R.;Handzlik-Orlik, G.;Okopien, B.",2012,Jun,,0,0,
253,Good response with zinc acetate monotherapy in an adolescent affected by severe Wilson disease,"We describe a 17-year-old girl with haemolytic anaemia as presentation of Wilson disease. The diagnosis was based on the findings of < 20 mg/dl ceruloplasmin serum level, Kayser-Fleischer ring and Coombs-negative haemolytic anaemia. Genetic testing revealed the presence of the H1069Q heterozygous mutation. The patient was treated with Zinc acetate monotherapy, with good response, maintened after 22 months. This case emphasizes the importance of recognizing atypical clinical presentation of Wilson disease, which must always be considered in patients with Coombs-negative haemolytic anaemia. The good clinical response to treatment with zinc acetate monotherapy in our case might lend to consider the use of zinc monotherapy as initial therapy also in symptomatic patients with Wilson disease under close clinical observation. Clinical trials are needed to provide evidence for use of zinc monotherapy as first-line therapy in symptomatic patients with Wilson disease.",Adolescent;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Remission Induction;Severity of Illness Index;*Zinc Acetate/tu [Therapeutic Use];FM5526K07A (Zinc Acetate),"Marazzi, M. G.;Giardino, S.;Dufour, C.;Serafino, M.;Sperli, D.;Giacchino, R.",2012,Mar-Apr,https://dx.doi.org/10.4081/pmc.2012.67,0,0,
254,Discovery of human zinc deficiency: 50 years later,"Essentiality of zinc for humans and its deficiency was recognized in 1963. During the past 50 years, it has become apparent that deficiency of zinc in humans is prevalent. Nutritional deficiency of zinc may affect nearly 2 billion subjects in the developing world. Consumption of cereal proteins high in phytate decreases the availability of zinc for absorption. Conditioned deficiency of zinc is also very common. Growth retardation, hypogonadism in males, rough skin, impaired immunity, neuro-sensory disorder and cognitive impairment are some of the clinical manifestations of zinc deficiency. Zinc is involved in many biochemical functions. Over 300 enzymes require zinc for their activation and nearly 2000 transcription factors require zinc for gene expression. Zinc is essential for cell mediated immunity. Zinc is also an effective antioxidant and anti-inflammatory agent. In therapeutic dosages, zinc has been used for the treatment of acute diarrhea in infants and children, common cold, Wilson's disease, sickle cell disease and for prevention of blindness in patients with age related macular degeneration. Copyright © 2012 Elsevier GmbH. All rights reserved.",Female;Humans;Immunity/ph [Physiology];Interleukin-2/me [Metabolism];Male;Tumor Necrosis Factor-alpha/me [Metabolism];*Zinc/df [Deficiency];0 (Interleukin-2);0 (Tumor Necrosis Factor-alpha);J41CSQ7QDS (Zinc),"Prasad, A. S.",2012,Jun,https://dx.doi.org/10.1016/j.jtemb.2012.04.004,0,0,
255,Myelopathy secondary to copper deficiency as a complication of treatment of Wilson's disease,"Wilson's Disease (WD) is an autosomal recessive disorder of copper metabolism resulting in a pathological accumulation of this metal, initially in the liver and later in other organs, mainly brain. Treatment with copper chelating agents and zinc salts results in a depletion of copper deposits and prevents or reverses the clinical manifestations. Copper deficiency may cause haematological and neurological changes, the latter principally being polyneuropathy and myelopathy. We report a patient with WD who developed a myelopathy associated with a deficiency of copper following prolonged treatment with D-penicillamine and zinc salts. Copyright © 2012 Elsevier Espana, S.L. and AEEH y AEG. All rights reserved.","Ceruloplasmin/an [Analysis];*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];*Chelation Therapy/ae [Adverse Effects];*Copper/df [Deficiency];Copper/pk [Pharmacokinetics];Copper/ur [Urine];Female;Gait Disorders, Neurologic/ci [Chemically Induced];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Magnetic Resonance Imaging;Middle Aged;Neurologic Examination;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Polyneuropathies/ci [Chemically Induced];Polyneuropathies/di [Diagnosis];Reflex, Abnormal;Sensation Disorders/ci [Chemically Induced];*Spinal Cord Diseases/ci [Chemically Induced];Spinal Cord Diseases/di [Diagnosis];*Zinc/ae [Adverse Effects];Zinc/pk [Pharmacokinetics];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Lozano Herrero, J.;Munoz Bertran, E.;Ortega Gonzalez, I.;Gomez Espin, R.;Lopez Espin, M. I.",2012,Dec,https://dx.doi.org/10.1016/j.gastrohep.2012.03.008,0,0,
256,Wilson's disease: an analysis of 28 Brazilian children,"OBJECTIVES: Clinical-laboratory and evolutionary analysis of twenty-eight patients with Wilson's disease. METHODS: Twenty-eight children (twelve females and sixteen males) with Wilson's disease were evaluated retrospectively between 1987 and 2009, with a follow-up of 72 months (1 - 240 months). The clinical, laboratory, and histologic features at diagnosis were recorded at the end of the study. RESULTS: The median age at diagnosis was 11 years (2 - 18 years). Twelve patients were asymptomatic, seven had hepatitis symptoms, five had raised aminotransferase levels, three had hepatomegaly associated with neurological disorders, one had fulminant hepatitis with hemolytic anemia, and six patients presented with a Kayser-Fleischer ring. A histological analysis revealed that six children had chronic hepatitis, seven had cirrhosis, two had steatosis, one had portal fibrosis, and one had massive necrosis. The treatment consisted of D-penicillamine associated with pyridoxine for 26 patients. Adverse effects were observed in the other two patients: one presented with uncontrollable vomiting and the other demonstrated elastosis perforans serpiginosa. At the end of the study, all 26 treated patients were asymptomatic. Twenty-four of the patients were treated with D-penicillamine and pyridoxine, and two were treated with trientine and zinc sulfate. A liver transplant was performed in one patient with fulminant hepatitis, but the final patient died 48 hours after admission to the intensive care unit. CONCLUSIONS: Family screenings associated with early treatment are important in preventing Wilson's disease symptoms and potentially fatal disease progression. The study suggests that Wilson's disease must be ruled out in children older than two years presenting with abnormal levels of hepatic enzymes because of the heterogeneity of symptoms and the encouraging treatment results obtained so far.","Adolescent;Aspartate Aminotransferases/bl [Blood];Biomarkers/bl [Blood];Brazil;Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Copper/tu [Therapeutic Use];Early Diagnosis;Family;Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;*Mass Screening/mt [Methods];Retrospective Studies;Zinc Sulfate/tu [Therapeutic Use];0 (Biomarkers);0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 2-6-1-1 (Aspartate Aminotransferases)","Kleine, R. T.;Mendes, R.;Pugliese, R.;Miura, I.;Danesi, V.;Porta, G.",2012,,,0,1,
257,Metals and the liver,"PURPOSE OF REVIEW: Hereditary liver diseases resulting in copper and iron overload may cause significant morbidity and mortality if not diagnosed and treated early. The goal of this review is to highlight the key publications on genetics, diagnosis and management of hemochromatosis and Wilson disease over the past 18 months. RECENT FINDINGS: Several recent advancements have been made in the genetic diagnosis of hemochromatosis and Wilson disease. Uncommon HFE mutations resulting in phenotypic hemochromatosis among C282Y heterozygotes have been identified from HFE gene sequencing. A serum ferritin less than 1000 mug/l in C282Y homozygotes was found to be associated with milder symptoms of hemochromatosis. Deferasirox was shown to reduce iron overload in patients with hemochromatosis and may be an option for patients who cannot tolerate phlebotomy. There was found to be evidence of genotype and phenotype correlation in Wilson disease, which can be diagnosed by genetic sequencing. A modified diagnostic guideline has been developed for children with Wilson disease with mild liver disease that increases the sensitivity and specificity of diagnosis. Also treatment with copper chelating agents has less hepatic treatment failures when compared with zinc monotherapy. SUMMARY: Advancements in diagnosis of hemochromatosis and Wilson disease may lead to earlier diagnosis and treatment with resulting decrease in morbidity and mortality.","Adenosine Triphosphatases/ge [Genetics];Cation Transport Proteins/ge [Genetics];*Copper/bl [Blood];Female;Ferritins/bl [Blood];Genotype;Hemochromatosis/bl [Blood];*Hemochromatosis/di [Diagnosis];Hemochromatosis/ge [Genetics];Hemochromatosis/th [Therapy];Hemochromatosis Protein;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Histocompatibility Antigens Class I/bl [Blood];Histocompatibility Antigens Class I/ge [Genetics];Humans;*Iron/bl [Blood];Male;*Membrane Proteins/bl [Blood];Mutation;Phlebotomy;0 (Cation Transport Proteins);0 (HFE protein, human);0 (Hemochromatosis Protein);0 (Histocompatibility Antigens Class I);0 (Membrane Proteins);789U1901C5 (Copper);9007-73-2 (Ferritins);E1UOL152H7 (Iron);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Maxwell, K. L.;Kowdley, K. V.",2012,May,https://dx.doi.org/10.1097/MOG.0b013e3283521d82,0,0,
258,Wilson's disease treated with penicillamine and lupus erythematosus: related or distinct entities?,"Systemic lupus erythematosus (SLE) has been reported to be associated to Wilson's disease, as a complication of treatment with penicillamine. Even though drug-induced lupus erythematosus (DILE) has some features in common with SLE, they are distinct entities. We report the case of a young girl who at the age of five had a diagnosis of Wilson's disease and she started therapy with penicillamine. Eight years after the beginning of therapy, she developed proteinuria, which was considered to be related to penicillamine. Two years later, she developed arthritis, malar rash and laboratory findings suggestive for lupus erythematosus. At the beginning her symptoms, due to the known association between penicillamine and DILE, were thought to be related to this treatment. In this hypothesis, she was referred to the Rheumatology Centre; zinc acetate was substituted for penicillamine and she started naproxen for the treatment of arthritis. Anyway, the subsequent clinical course and laboratory findings led us to a diagnosis of idiopathic SLE. A renal biopsy detected massive mesangiocapillary proliferation with subendothelial deposits (wire loops) and duplication of glomerular basement membrane (active diffuse global proliferative lupus nephritis, class IV G A). To our knowledge, this is the first report of an association between Wilson's disease and SLE.","Adolescent;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lupus Erythematosus, Systemic/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine)","Dell'era, L.;Boati, E.;Nebbia, G.;Corona, F.",2012,Feb,,0,0,
259,Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators,"Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.",Animals;*Biomimetics/mt [Methods];Chelating Agents/ch [Chemistry];Chelating Agents/me [Metabolism];Chelating Agents/pd [Pharmacology];Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];*Drug Design;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Intracellular Space/de [Drug Effects];*Intracellular Space/me [Metabolism];Penicillamine/ch [Chemistry];*Penicillamine/me [Metabolism];*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Delangle, P.;Mintz, E.",2012,Jun 07,https://dx.doi.org/10.1039/c2dt12188c,0,0,
260,[Diagnosis and care of Wilson disease with neurological revelation],"Wilson disease is an autosomal recessive disease that produces a copper accumulation in many organs, initially in the liver, progressing to liver cirrhosis, and in the brain, with different neurologic symptoms. Diagnosis is based on clinical, biochemical, and genetic tests. Different treatments based on chelating agents may help reduce the disease's spontaneous morbidity and mortality. We describe three patients who presented Wilson disease before 18 years of age, with initial neurologic symptoms between 1998 and 2010. After comparison with literature reports, their clinical symptoms, progression, and care allowed us to propose a treatment algorithm. Neurologic symptoms are present in 35% of the patients with Wilson disease such as dystonia, extrapyramidal syndrome, dysarthria, dysphagia, and psychiatric symptoms. The time to diagnosis remains too long and may account for the increased severity of the illness encountered and problems treating these patients. The first treatment choice must be triethylenetetramine, which causes fewer side effects of initial worsening of symptoms compared to D-penicillamine. Zinc therapy is the first treatment for asymptomatic patients or those on maintenance treatment. Finally, liver transplantation is a potential treatment even if the patient presents severe neurological disability because it may improve clinical symptoms. However, further research is warranted on this matter. Copyright A© 2011 Elsevier Masson SAS. All rights reserved.",Adolescent;Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation;Magnetic Resonance Imaging;Male;*Nervous System Diseases/di [Diagnosis];Nervous System Diseases/ge [Genetics];*Neurologic Examination;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Wagner, S.;Brunet, A. S.;Bost, M.;Lachaux, A.;Broussolle, E.;Des Portes, V.;Lion-Francois, L.",2012,Mar,https://dx.doi.org/10.1016/j.arcped.2011.12.009,0,0,
261,Serum 'free' copper in Wilson disease,"BACKGROUND: The relationship between serum 'free' copper and urine copper in patients with Wilson disease has not been explored. AIM: The object of this study is to ascertain if there is a direct relationship between these two parameters. METHOD: The case notes of 320 patients with Wilson disease, seen between 1960 and 1987, have been reviewed. Eighty of these patients had received no treatment before referral and the results of serum 'free' copper and urine copper on admission and at one year of treatment have been analysed. RESULTS: Except for patients with acute haemolysis, the ratio between 'free' serum copper and urine copper before treatment, on average, is around 7:1, after treatment this falls to around 5:1. But results show a wide scatter and there is no direct linear relationship. CONCLUSION: The term 'free' copper is misleading and should be replaced by the more cumbersome but accurate term 'noncaeruloplasmin bound copper'. Most 'free' copper is complexed to albumin and is only available for excretion if there is significant protein loss by the kidneys.","Adolescent;Adult;Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;*Copper/bl [Blood];*Copper/ur [Urine];*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ur [Urine];Humans;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Young Adult;0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Walshe, J. M.",2012,May,https://dx.doi.org/10.1093/qjmed/hcr229,0,0,
262,Metal element excretion in 24-h urine in patients with Wilson disease under treatment of D-penicillamine,"Wilson disease is an inherited autosomal recessive disorder causing copper accumulation and consequent toxicity. D-Penicillamine, a potent metal chelator, is an important therapy for Wilson disease. To investigate the changes of metal elements under the treatment of D-penicillamine, we determined the levels of Cu, Zn, Mg, Ca, Fe, Se, Mn, Pb, Hg, Cd, As, Tl, and Al by ICP-MS in 24-h urine of 115 Wilson disease patients who had received treatment with D: -penicillamine for 1 month to 22 years at maintenance doses, as well as 115 age-matched, healthy controls. The levels of Cu, Mg, Ca, Zn, Hg, Pb, Tl, Cd, and Mn in the 24-h urine of the cases were significantly higher than those of the controls (P<0.05), and the observed increases in the levels of Mg, Ca, and Zn were directly correlated with the treatment duration with Pearson Correlation Coefficient (R) of 0.356 (Mg), 0.329 (Ca), and 0.313 (Zn), respectively (P<0.05). On the other hand, the levels of Al and As in the 24-h urine were lower than those of the controls (P<0.05) and were negatively correlated with the treatment time with R of -0.337 (Al) and -0.398 (As), respectively, (P<0.05). Thus, this study indicates that the levels of metal elements may be altered in patients with Wilson disease under the treatment of D-penicillamine.","Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ur [Urine];Humans;Male;*Metals/ur [Urine];Middle Aged;*Penicillamine/tu [Therapeutic Use];Time Factors;Treatment Outcome;Young Adult;0 (Chelating Agents);0 (Metals);GNN1DV99GX (Penicillamine)","Huang, L.;Yu, X.;Zhang, J.;Liu, X.;Zhang, Y.;Jiao, X.;Yu, X.",2012,May,https://dx.doi.org/10.1007/s12011-011-9250-3,0,0,
263,"Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment","Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson's disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome. Wilson's disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson's disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson's disease should be implemented in infants. Patients with Wilson's disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson's disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention.","Age Factors;Animals;Carcinoma, Hepatocellular/et [Etiology];Carcinoma, Hepatocellular/pc [Prevention & Control];Copper/df [Deficiency];*Copper/me [Metabolism];Copper/to [Toxicity];Cutis Laxa/di [Diagnosis];*Cutis Laxa/pp [Physiopathology];Cutis Laxa/th [Therapy];Ehlers-Danlos Syndrome/di [Diagnosis];*Ehlers-Danlos Syndrome/pp [Physiopathology];Ehlers-Danlos Syndrome/th [Therapy];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;Infant;Infant, Newborn;Liver Neoplasms/et [Etiology];Liver Neoplasms/pc [Prevention & Control];Mass Screening/mt [Methods];Menkes Kinky Hair Syndrome/di [Diagnosis];*Menkes Kinky Hair Syndrome/pp [Physiopathology];Menkes Kinky Hair Syndrome/th [Therapy];789U1901C5 (Copper);Occipital horn syndrome","Kodama, H.;Fujisawa, C.;Bhadhprasit, W.",2012,Mar,,0,0,
264,Manifestations and evolution of Wilson disease in pediatric patients carrying ATP7B mutation L708P,"OBJECTIVES: The aim of the study was to characterize a group of 11 pediatric patients, ages 3 to 13 years, affected by Wilson disease (WD) in the island of Gran Canaria, Spain. PATIENTS AND METHODS: Genetic, biochemical, and pathological features, together with their response to treatment and clinical evolution, have been analyzed for this group of patients. RESULTS: Genetically, the group was rather homogeneous, with an extremely high prevalence of the L708P mutation (4 homozygotes and 5 heterozygotes). Despite being initially screened because of asymptomatic hypertransaminemia, all of the patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is greatly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content, were found to be of great diagnostic value, whereas urine copper measurements were found to be much less conclusive. All of the patients responded well to treatment with D-penicillamine with no documented adverse reactions. CONCLUSIONS: The patients in Gran Canaria constitute, overall, one of the largest groups of patients with WD with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.","*Adenosine Triphosphatases/ge [Genetics];Adolescent;*Cation Transport Proteins/ge [Genetics];Ceruloplasmin/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;*Copper/me [Metabolism];Disease Progression;Female;Genotype;*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/me [Metabolism];*Liver/pa [Pathology];Male;*Mutation;Penicillamine/tu [Therapeutic Use];0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Pena-Quintana, L.;Garcia-Luzardo, M. R.;Garcia-Villarreal, L.;Arias-Santos, M. D.;Garay-Sanchez, P.;Santana, A.;Gonzalez-Santana, D.;Ramos-Varela, J. C.;Rial-Gonzalez, R.;Tugores, A.",2012,Jan,https://dx.doi.org/10.1097/MPG.0b013e318230130c,0,0,
265,Behavioural and psychiatric disorders in paediatric Wilson's disease,An 11-year-old boy was treated since 6-years-old with methylphenidate for combined attention deficit and hyperactivity disorder. At age nine his behaviour had worsened and he started to have phobias. One year later persistent hypertransaminasemia was found. Physical examination showed a dysdiadocokinesia. Laboratory investigation revealed a low caeruloplasmin and augmented basal urinary copper with a positive postpenicillamine test. Liver biopsy showed high liver copper (853 micro g/g) and brain MRI was normal. D-penicillamine and zinc acetate were started without side effects. ATP7B gene mutation was confirmed after treatment initiation.,Child;*Hepatolenticular Degeneration/co [Complications];Humans;Male;*Mental Disorders/et [Etiology],"Silva, F.;Nobre, S.;Campos, A. P.;Vasconcelos, M.;Goncalves, I.",2011,Aug 04,https://dx.doi.org/10.1136/bcr.05.2011.4249,0,0,
266,Neurological Wilson disease in children: a three years experience from Multan,"OBJECTIVE: To describe the neurological manifestations, results of investigations and response to treatment in Wilson disease in children from Multan. METHODS: This cross sectional study was conducted at Neurology Department of Children Hospital and Institute of Child Health Multan from June 2005 to May 2008. Fifty children were included in this study. Age at onset of symptoms, sex, duration of symptoms, presenting complaints, consanguinity among parents, family history and response to treatment was noted. Chi square test was used to measure relationship between variables and response to treatment. P value of less than 0.05 was taken as significant. RESULTS: Of the 50 cases studied, 48 were index cases and two were diagnosed on screening. Male female ratio was 2.1:1. Mean age at onset of symptoms was 9.06 +/- 2.65 years. Dystonia, dysarthria and cognitive decline was seen in 92%, drooling in 68%, tremors in 52%, chorea in 24% and seizures in 12% of children. Kayser Fleischer rings and elevated 24 hours urinary copper after penicillamine challenge, 1567 +/- 167.35 microg/day was present in all 50 children. Twenty two (44%) children showed early response, 24 (48%) late response and 4 (8%) children showed no response after one year of treatment. Late, greater than 10 years of age at onset of symptoms, less than 6 months duration of symptoms and urinary copper excretion of less than 1000 microg/day were found statistically significant factors for early response to treatment. CONCLUSION: In the study population, dystonia, dysarthria and cognitive decline were the commonest presentations. Twenty four hour urinary copper was found helpful for diagnosis. Penicillamine was found to be an effective drug for treatment as overall response was noted in 92% of children.","Adolescent;Age Distribution;Age of Onset;Astringents/tu [Therapeutic Use];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Copper/me [Metabolism];*Copper/ur [Urine];Cross-Sectional Studies;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ep [Epidemiology];Humans;Incidence;Male;Nervous System Diseases/et [Etiology];Neurologic Examination;Pakistan/ep [Epidemiology];Penicillamine/tu [Therapeutic Use];Pyridoxine/tu [Therapeutic Use];Sex Distribution;Treatment Outcome;Vitamin B Complex/tu [Therapeutic Use];Zinc Sulfate/tu [Therapeutic Use];0 (Astringents);0 (Chelating Agents);12001-76-2 (Vitamin B Complex);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine)","Noureen, N.;Rana, M. T.",2011,Aug,,0,0,
267,Acute Gallbladder Hydrops and Arthritis: unusual initial manifestations of Wilson's Disease (WD): Case Report,"Wilson disease (WD) is an autosomal recessive disorder, in which copper is deposited in the liver, brain, cornea and kidneys. The clinical presentation is variable, with fully expressed disease manifesting cirrhosis, neurologic damage and Kayser-Fleischer (K-F) ring on the cornea. A 24-year-old patient developed right upper quadrant pain with a palpable mass and a swelling of the right talocrural articulation. X-rays were uneventful, but the routine examination of hepatic enzymes discovered a 6-8 fold increase in SGPT, SGOT and AST. Antibodies for hepatitis B, C were normal, as well as the ANA, ANCA, antimytochondrial and anti-smooth muscle antibodies. Ultrasound of the abdomen revealed extremely dilated hepatic, cystic ducts as well as gallbladder. A large, oedematous gallbladder with yellow green bile was removed, the liver was found to be cirrhotic, but as the operative bleeding was abundant a biopsy was not done. Serum ceruloplasmin was low [0.160 g/l (normal 0.204-0.407)], serum copper 12.7 micro mol/l (11.0-24.4), transaminasis: always very high, in the last months normal/slightly elevated. Urine copper: 1.0 micro mol/24 h (>9.44). As first seen the proband had tremor, dysarthria, dystonia and K-F ring on the cornea. After 10 months of treatment with penicillamine his transaminases normalized, the tremor, dysarthria, dystonia initially got worse and then ameliorated. The coagulation times are ameliorated, but not yet normalized. Mutational analysis has shown that the proband is homozygote for c.3207 C->A, p.H1069Q while his parents are heterozygotes. His sister is a healthy non-carrier. In brief, we describe an unusual presentation of WD, with gallbladder hydrops and talocrural arthritis in a patient with complete clinical manifestations of the disease.",Adenosine Triphosphatases/ge [Genetics];Arthritis/di [Diagnosis];Arthritis/et [Etiology];*Arthritis;Cation Transport Proteins/ge [Genetics];*Ceruloplasmin/an [Analysis];Chelating Agents/ad [Administration & Dosage];*Cholecystectomy/mt [Methods];Copper/me [Metabolism];Corneal Diseases/di [Diagnosis];Corneal Diseases/et [Etiology];Edema/di [Diagnosis];Edema/et [Etiology];Edema/su [Surgery];*Edema;Gallbladder Diseases/di [Diagnosis];Gallbladder Diseases/et [Etiology];Gallbladder Diseases/su [Surgery];*Gallbladder Diseases;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver Cirrhosis/di [Diagnosis];Liver Cirrhosis/me [Metabolism];Liver Cirrhosis/pp [Physiopathology];*Liver Cirrhosis;Liver Function Tests/mt [Methods];Male;*Penicillamine/ad [Administration & Dosage];Treatment Outcome;Young Adult;0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine),"Gucev, Z. S.;Pop-Jordanova, N.;Calovska, V.;Tasic, V.;Slavevska, N.;Laban, N.;Noli, M. C.;Lepori, M. B.;Loudianos, G.",2011,,,0,0,
268,Oxcarbazepine-responsive paroxysmal kinesigenic dyskinesia in Wilson disease,"A 22-year-old man presented with a 2-year history of tremor of the upper limbs associated to behavioral disorders. A magnetic resonance imaging of the brain showed hyperintensity in the right frontoparietal region, basal ganglia, particularly in the caudate nucleus, midbrain, and pons in T2 sequences, fluid-attenuated inversion recovery, and diffusion. Serum ceruloplasmin levels were 4 mg/dL (range, 20-45 mg/dL), and 24-hour urine cooper excretion was increased up to 223 micro g (10-40 micro g/24 hours). Slit lamp examination demonstrated the presence of a Kayser-Fleischer ring and penicillamine treatment started. Four months later, he developed episodes of paroxysmal dystonic posturing of his left arm, which increased in frequency reaching 2 or 3 attacks per hour. They were triggered by voluntary movements and forced him to adopt an abnormal flexion of the left forearm over the left bicep and were preceded by a tightening sensation of the left forearm muscles. Episodes completely remitted with oxcarbazepine.",*Carbamazepine/aa [Analogs & Derivatives];Carbamazepine/tu [Therapeutic Use];Dystonia/ci [Chemically Induced];*Dystonia/di [Diagnosis];Dystonia/dt [Drug Therapy];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Movement Disorders/di [Diagnosis];Movement Disorders/dt [Drug Therapy];*Penicillamine/ae [Adverse Effects];Young Adult;33CM23913M (Carbamazepine);GNN1DV99GX (Penicillamine);VZI5B1W380 (oxcarbazepine);Familial paroxysmal dystonia,"Micheli, F.;Tschopp, L.;Cersosimo, M. G.",2011,Nov-Dec,https://dx.doi.org/10.1097/WNF.0b013e3182348964,0,0,
269,A clinical study of Wilson's disease: The experience of a single Egyptian Paediatric Hepatology Unit,"BACKGROUND AND STUDY AIMS: Most paediatric patients with Wilson's disease (WD) present with hepatic manifestations, but some may have neurologic or psychiatric features. Our aim was to define the clinical, biochemical features and the outcome of therapy of a group of Egyptian children diagnosed with WD. PATIENTS AND METHODS: The study was carried out at the Paediatric Hepatology Unit at Cairo University Children's Hospital, Egypt; 54 patients were diagnosed with WD from 1996 to 2009. The diagnosis was based on low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge and/or the presence of Kayser-Fleischer (K-F) rings. RESULTS: The clinical presentation was as follows: hepatic presentation in 33 patients (61%), hepato-neurologic 3 (5.5%), neurologic 5 (9.3%) and presymptomatic 13 (24%). Twelve couples had more than one affected sib. Increased urinary copper concentrations before or after D-penicillamine challenge was found in all patients, low serum ceruloplasmin in 97% and K-F rings in 31.5%. All patients were treated with penicillamine and zinc sulphate except one presymptomatic case who was treated with zinc sulphate only. Three patients underwent liver transplantation and eight patients died after a median duration of treatment of 6 months (1-36). The hepatic symptoms improved with treatment but the neurological symptoms remained stationary. CONCLUSIONS: Clinical and biochemical assays remain the standard for diagnosis of WD. Penicillamine and zinc therapy can effectively treat WD with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage WD. Screening for presymptomatic sibs is of utmost importance. Copyright A© 2011 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.","Adolescent;Biomarkers/bl [Blood];Biomarkers/ur [Urine];*Ceruloplasmin/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;*Copper/ur [Urine];Diagnosis, Differential;Egypt;Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Humans;Liver/me [Metabolism];Liver/pa [Pathology];*Liver Transplantation/mt [Methods];Male;*Penicillamine/tu [Therapeutic Use];Retrospective Studies;0 (Biomarkers);0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","El-Karaksy, H.;Fahmy, M.;El-Raziky, M. S.;El-Hawary, M.;El-Sayed, R.;El-Koofy, N.;El-Mougy, F.;El-Hennawy, A.;El-Shabrawi, M.",2011,Sep,https://dx.doi.org/10.1016/j.ajg.2011.07.007,0,1,
270,Zinc monotherapy from time of diagnosis for young pediatric patients with presymptomatic Wilson disease,"In 4 young pediatric patients with presymptomatic Wilson disease, we found zinc monotherapy beginning at time of diagnosis to be safe and highly effective for follow-up intervals between 1 and 2 years. Such maintenance therapy with zinc can maintain urinary copper excretion between 1 and 3 mug . kg(-1) . day.","Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Asymptomatic Diseases/th [Therapy];Child;Child, Preschool;Copper/bl [Blood];Copper/ur [Urine];Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);J41CSQ7QDS (Zinc)","Mizuochi, T.;Kimura, A.;Shimizu, N.;Nishiura, H.;Matsushita, M.;Yoshino, M.",2011,Oct,https://dx.doi.org/10.1097/MPG.0b013e31821d5abe,0,0,
271,A case of isolated elevated copper levels during pregnancy,"INTRODUCTION: Outside of Wilson's Disease, abnormal copper metabolism is a rare condition. In pregnancy, excess copper levels can be associated with intrauterine growth restriction, preeclampsia and neurological disease. CASE REPORT: A 32 year old Gravida 4 para 2012 with an obstetrical history complicated by elevated copper levels presented for routine prenatal care. Her children had elevated copper levels at birth, with her firstborn child being diagnosed with autism and suffering three myocardial infarctions and being treated for elevated copper levels. During her prior pregnancies, she declined treatment for her elevated copper levels. During this pregnancy, she had declined chelation therapy and instead choose zinc therapy. She delivered a healthy infant with normal copper levels. CONCLUSION: Alterations in copper metabolism are rare, the consequences in pregnancy can be devastating. While isolated elevations of copper in pregnancy is exceedingly rare, it is treated the same as Wilson's disease. The goal is to prevent fetal growth restricting and neurological sequelae in the newborn and preeclampsia in the mother. Counseling, along with treatment options and timely delivery can greatly improve neonatal and maternal outcome.","Adult;*Copper/bl [Blood];Female;Humans;Infant, Newborn;Male;Pregnancy;Pregnancy Complications/bl [Blood];*Pregnancy Complications/pc [Prevention & Control];*Pregnancy, High-Risk/bl [Blood];Secondary Prevention;*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Walker, L. R.;Rattigan, M.;Canterino, J.",2011,,https://dx.doi.org/10.1155/2011/385767,0,0,
272,Excess copper chelating therapy for Wilson disease induces anemia and liver dysfunction,"A 37-year-old man was diagnosed with Wilson disease at the age of 14. His first manifestations were neurological. He was treated with trientine for more than 10 years and suffered from anemia and liver dysfunction. Wilson disease is a genetic disorder characterized by accumulation of copper in the body. Excess copper is toxic, but copper is an essential trace element. Copper-binding ceruloplasmin is important for iron metabolism. Excess copper chelating treatment-induced anemia and iron deposition in the liver was suspected. Proper monitoring of copper status is important for the management of Wilson disease.",Adult;Anemia/bl [Blood];*Anemia/ci [Chemically Induced];Ceruloplasmin/me [Metabolism];Chelating Agents/ad [Administration & Dosage];*Chelating Agents/ae [Adverse Effects];*Chelation Therapy/ae [Adverse Effects];Copper/me [Metabolism];*Copper;Hemochromatosis/et [Etiology];Hemochromatosis/me [Metabolism];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Iron/me [Metabolism];*Liver Diseases/et [Etiology];Liver Diseases/me [Metabolism];Male;Trientine/ad [Administration & Dosage];Trientine/ae [Adverse Effects];0 (Chelating Agents);789U1901C5 (Copper);E1UOL152H7 (Iron);EC 1-16-3-1 (Ceruloplasmin);SJ76Y07H5F (Trientine),"Harada, M.;Miyagawa, K.;Honma, Y.;Hiura, M.;Shibata, M.;Matsuhashi, T.;Abe, S.;Harada, R.;Tabaru, A.",2011,,,0,0,
273,Hepatocellular carcinoma in a case of Wilson's disease treated with radiofrequency ablation therapy,"A 37-year-old Japanese man was diagnosed with liver cirrhosis due to Wilson's disease in 2001 and treated with D-penicillamine. Thereafter, he was admitted to our hospital for further examination of a space occupying lesion in the liver. The patient was diagnosed with hepatocellular carcinoma (HCC) (7th segment, 2.5 cm in diameter) in May 2010 and treated with radiofrequency ablation therapy. Biopsy findings from a non-cancerous area revealed a fatty liver, though cirrhotic nodules were not found. Long-term treatment for Wilson's disease may improve hepatic fibrosis, and careful screening for HCC by abdominal imaging is needed in such cases.","Adult;Carcinoma, Hepatocellular/di [Diagnosis];Carcinoma, Hepatocellular/et [Etiology];*Carcinoma, Hepatocellular/th [Therapy];Catheter Ablation/mt [Methods];*Catheter Ablation;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Neoplasms/di [Diagnosis];Liver Neoplasms/et [Etiology];*Liver Neoplasms/th [Therapy];Male","Ikegawa, S.;Hiraoka, A.;Shimizu, Y.;Hidaka, S.;Tazuya, N.;Ichiryu, M.;Nakahara, H.;Tanabe, A.;Tanihira, T.;Hasebe, A.;Miyamoto, Y.;Ninomiya, T.;Hirooka, M.;Kumagi, T.;Abe, M.;Hiasa, Y.;Onji, M.;Michitaka, K.",2011,,,0,0,
274,Phenotypic and genetic characterization of a cohort of pediatric Wilson disease patients,"BACKGROUND: In Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. The aim of this study is to highlight the clinical, laboratory and genetic characteristics of this disease in our pediatric population as well as to report our experience with both treatment options and outcome. METHODS: The study included 77 patients from 50 unrelated families (62 were followed up for a mean period of 58.9 +/- 6.4 months and 27 were asymptomatic siblings). Data were collected retrospectively by record analysis and patient interviews. Diagnosis was confirmed by sequencing of the ATP7B gene in 64 patients. RESULTS: Our patients had unique characteristics compared to other populations. They had a younger age of onset (median: 10 years), higher prevalence of Kayser-Fleischer rings (97.6% in the symptomatic patients), low ceruloplasmin (93.5%), high rate of parental consanguinity (78.9%) as well as a more severe course. 71.42% of those on long term D-penicillamine improved or were stable during the follow up with severe side effects occurring in only 11.5%. Preemptive treatment with zinc monotherapy was an effective non-toxic alternative to D-penicillamine. Homozygous mutations were found in 85.7%, yet limited by the large number of mutations detected, it was difficult to find genotype-phenotype correlations. Missense mutations were the most common while protein-truncating mutations resulted in a more severe course with higher incidence of acute liver failure and neurological symptoms. CONCLUSIONS: Egyptian children with Wilson disease present with early Kayser-Fleischer rings and early onset of liver and neurological disease. The mutational spectrum identified differs from that observed in other countries. The high rate of homozygous mutations (reflecting the high rate of consanguinity) may potentially offer further insights on genotype-phenotype correlation.","*Adenosine Triphosphatases/ge [Genetics];Adolescent;Adult;Age of Onset;*Cation Transport Proteins/ge [Genetics];Child;Corneal Diseases/ge [Genetics];Egypt;Female;Follow-Up Studies;Genetic Association Studies;*Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver Diseases/ge [Genetics];Male;Mutation, Missense;Nervous System Diseases/ge [Genetics];Retrospective Studies;Severity of Illness Index;0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Abdel Ghaffar, T. Y.;Elsayed, S. M.;Elnaghy, S.;Shadeed, A.;Elsobky, E. S.;Schmidt, H.",2011,Jun 17,https://dx.doi.org/10.1186/1471-2431-11-56,0,1,
275,Prognostic significance of neurologic examination findings in Wilson disease,"BACKGROUND: Wilson disease patients present with any of several neurologic phenotypes, and their treated outcomes vary widely. Our goal was to determine whether presenting clinical features of neurologic Wilson disease (WD) predict longer term neurologic outcomes in patients receiving anticopper treatment. METHODS: Patients enrolled in four WD treatment trials received a standardized neurologic examination at trial enrollment and then at pre-specified intervals following anticopper therapy, initially with tetrathiomolybdate or trientine and then with zinc. The examination scored patients' motor signs, including tremor, rigidity, dystonia, dyarthria, and gait. The Total Score was obtained by summing these subscores. Eighty-six patients were included in our analysis, with a mean follow-up of 34.7 months. Retrospectively, the analysis compared scaled and unscaled sign subscores at enrollment and follow-up with change in the Total Score, using a generalized estimating equations approach. RESULTS: In the primary analysis, improvement in the Total Score was best predicted by sign subscores for tremor (beta -0.7, p = 0.006), gait abnormalities (beta -3.7, p < 0.001), and speech (beta = -1.3, p = 0.05). Dystonia (beta = 1.8, p < 0.001) and facial expression (beta = 1.9, p = 0.03) were associated with worsening Total Score. Of the motor signs followed individually, dystonia proved most resistant to treatment. CONCLUSIONS: This is the first large-scale prospectively acquired study assessing prognostic significance of specific neurologic signs in WD. Our data support the historical observations that tremor is a favorable prognostic sign while dystonia is relatively refractory to treatment in WD. Copyright © 2011 Elsevier Ltd. All rights reserved.",Adult;Chelating Agents/tu [Therapeutic Use];Dystonia/et [Etiology];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Molybdenum/tu [Therapeutic Use];*Neurologic Examination;Prognosis;Risk Factors;Tremor/et [Etiology];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Burke, J. F.;Dayalu, P.;Nan, B.;Askari, F.;Brewer, G. J.;Lorincz, M. T.",2011,Aug,https://dx.doi.org/10.1016/j.parkreldis.2011.05.002,0,1,
276,The pattern of urinary copper excretion and its response to treatment in patients with Wilson's disease,"BACKGROUND: It is generally accepted that patients with Wilson's disease excrete excess copper in urine. However, there has been no study, on a large series of patients, as to whether there are differences in the rate of excretion at different stages of the disease or what changes may be expected after treatment. DESIGN: The present study follows from an analysis of the results of urinary copper excretion of 192 patients with Wilson's disease seen between 1955 and 2000. These patients were divided into three groups, pre-symptomatic, hepatic and neurological Wilson's disease. Patients were studied for basal pre-treatment, 24-h urinary copper excretion and for 6 h after a test dose of 500 mg penicillamine. The tests were repeated after approximately 1 and 2 years of chelation therapy with either penicillamine, or in a small minority of cases, trientine. RESULTS: The basal, pre-treatment copper excretion was the lowest in pre-symptomatic patients (207.93 micro g/24 h) and the highest in the hepatic patients (465.75 micro g/24 h). Those with neurological Wilson's disease gave an intermediate figure (305.58 micro g/24 h). The response to penicillamine was the highest in the neurological patients and the lowest in the pre-symptomatic group. After 1 and 2 years of treatment all groups showed significant falls in both the basal and the after penicillamine rate of excretion of copper. The small subgroup treated with trientine, rather than penicillamine, showed similar results. CONCLUSIONS: The rate of copper excretion in patients with Wilson's disease shows wide variation from patient to patient, but in general patients with pre-symptomatic disease excrete less copper than those with symptomatic disease. All groups show a great increase when challenged with penicillamine. After 1 and 2 years of treatment, there is significant decrease in copper excretion in both basal and after penicillamine challenge. This presumably indicates a reduction in the body load of copper.","Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Chelation Therapy/mt [Methods];Child;Child, Preschool;*Copper/ur [Urine];Disease Progression;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ur [Urine];Humans;Penicillamine/tu [Therapeutic Use];Young Adult;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Walshe, J. M.",2011,Sep,https://dx.doi.org/10.1093/qjmed/hcr073,0,0,
277,[Neurological complications of Wilson's disease],,"Animals;Basal Ganglia Diseases/et [Etiology];Basal Ganglia Diseases/pa [Pathology];Central Nervous System/me [Metabolism];Central Nervous System/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Chelation Therapy;Copper/pk [Pharmacokinetics];Epilepsy/et [Etiology];Epilepsy/pp [Physiopathology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/px [Psychology];Hepatolenticular Degeneration/su [Surgery];Humans;Liver Transplantation;*Mental Disorders/et [Etiology];Models, Animal;*Movement Disorders/et [Etiology];Necrosis;Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Burgos, A.;Bermejo, P. E.",2011,Oct 08,https://dx.doi.org/10.1016/j.medcli.2011.02.027,0,0,
278,Alterations of lipid metabolism in Wilson disease,"INTRODUCTION: Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date. PATIENTS AND METHODS: This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination). RESULTS: A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides. CONCLUSION: Contradictory to previous reports using WD animal models (Atp7b-/- and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment.",Animals;Cholesterol/bl [Blood];Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;*Lipid Metabolism;Lipids/bl [Blood];Male;Rats;Zinc/tu [Therapeutic Use];0 (Lipids);97C5T2UQ7J (Cholesterol);J41CSQ7QDS (Zinc),"Seessle, J.;Gohdes, A.;Gotthardt, D. N.;Pfeiffenberger, J.;Eckert, N.;Stremmel, W.;Reuner, U.;Weiss, K. H.",2011,May 19,https://dx.doi.org/10.1186/1476-511X-10-83,0,0,
279,Wilson's disease in southern Brazil: a 40-year follow-up study,"BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5% had a European ancestor. The mean age at the initial symptom presentation was 23.3 +/- 9.3 years, with a delay of 27.5 +/- 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9%), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6%) and neuropsychiatric symptoms (25%). Kayser-Fleischer rings were identified in 55.6% of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8%). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2% of these patients. Chronic liver disease was detected in 68% of the patients with hepatic symptoms. 94.2% of all the patients were treated with D-penicillamine for a mean time of 129.9 +/- 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8% of the patients had a stable or improved outcome, and the overall survival rate was 90.1%. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.",Adolescent;Adult;Age Distribution;Age Factors;Brazil/ep [Epidemiology];Chelating Agents/tu [Therapeutic Use];Child;Female;Follow-Up Studies;Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/eh [Ethnology];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver/pa [Pathology];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Retrospective Studies;Sex Distribution;Survival Rate;Time Factors;Treatment Outcome;Young Adult;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Bem, R. S.;Muzzillo, D. A.;Deguti, M. M.;Barbosa, E. R.;Werneck, L. C.;Teive, H. A.",2011,,,0,1,
280,D-penicillamine elastosis perforans serpiginosa: description of two cases and review of the literature,"Long term D-penicillamine (DPA) therapy to treat Wilson disease can induce elastosis perforans serpiginosa (EPS), a very rare degenerative skin disease characterized by a transepidermal elimination of elastic fiber aggregates. The iatrogenous disease depends on DPA capacity to chelate copper and cause its depletion. Lysyl-oxidase is a copper dependent enzyme crucial to the dermal elastic fiber cross-linking, which is strongly affected by DPA copper depletion. Direct binding of the drug to collagen precursors also affects elastic fiber assemblage and maturation. The abnormal elastin accumulates into the middle dermis and produces a characteristic bramble brush or ""lumpy-bumpy"" appearance. In this way it acts as a foreign body and is progressively extruded through the epidermis. Clinically, the disease presents with multiple firm keratotic papules and nodules arranged in annular plaques over the neck, axillae, antecubital fossae, and forearms. The rarity of the disease frequently causes misdiagnoses and the process continues unabated causing concerns about systemic elastopathy.",Adult;*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Cryotherapy;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Skin Diseases/ci [Chemically Induced];*Skin Diseases/di [Diagnosis];Skin Diseases/th [Therapy];Treatment Outcome;Young Adult;Zinc/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);Elastosis perforans serpiginosa,"Atzori, L.;Pinna, A. L.;Pau, M.;Aste, N.",2011,Apr 15,,0,0,
281,Copper deficiency in Wilson's disease: peripheral neuropathy and myelodysplastic syndrome complicating zinc treatment,,Adult;*Copper/df [Deficiency];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Muscular Atrophy/ci [Chemically Induced];Muscular Atrophy/me [Metabolism];*Myelodysplastic Syndromes/ci [Chemically Induced];Myelodysplastic Syndromes/me [Metabolism];*Peripheral Nervous System Diseases/ci [Chemically Induced];Peripheral Nervous System Diseases/me [Metabolism];*Zinc Sulfate/ae [Adverse Effects];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper),"Cortese, A.;Zangaglia, R.;Lozza, A.;Piccolo, G.;Pacchetti, C.",2011,Jun,https://dx.doi.org/10.1002/mds.23520,0,0,
282,Undetectable serum alkaline phosphatase activity in a patient with fulminant hepatic failure and hemolytic anemia,,"Adult;*Alkaline Phosphatase/bl [Blood];Anemia, Hemolytic/bl [Blood];Anemia, Hemolytic/co [Complications];*Anemia, Hemolytic/di [Diagnosis];Anemia, Hemolytic/th [Therapy];Chelating Agents/ad [Administration & Dosage];Chelating Agents/tu [Therapeutic Use];Copper/ur [Urine];Diagnosis, Differential;Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Liver Failure, Acute/bl [Blood];Liver Failure, Acute/co [Complications];*Liver Failure, Acute/di [Diagnosis];Liver Failure, Acute/th [Therapy];Liver Function Tests;Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];Plasmapheresis;Treatment Outcome;Young Adult;0 (Chelating Agents);789U1901C5 (Copper);EC 3-1-3-1 (Alkaline Phosphatase);GNN1DV99GX (Penicillamine)","Oosthuizen, N. M.",2011,Mar,https://dx.doi.org/10.1373/clinchem.2010.152447,0,0,
283,"Zinc toxicity: from ""no, never"" to ""hardly ever""",,*Chelating Agents/ad [Administration & Dosage];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Trace Elements/ad [Administration & Dosage];*Trace Elements/ae [Adverse Effects];Trace Elements/pk [Pharmacokinetics];Zinc/ad [Administration & Dosage];*Zinc/ae [Adverse Effects];Zinc/pk [Pharmacokinetics];0 (Chelating Agents);0 (Trace Elements);J41CSQ7QDS (Zinc),"Roberts, E. A.",2011,Apr,https://dx.doi.org/10.1053/j.gastro.2011.02.028,0,0,
284,Risks and benefits of copper in light of new insights of copper homeostasis,"Copper is an essential micronutrient involved in a variety of biological processes indispensable to sustain life. At the same time, it can be toxic when present in excess, the most noticeable chronic effect being liver damage. Potent, efficient regulatory mechanisms control copper absorption in the digestive tract and copper biliary excretion; absorption ranges between 12 and 60% in humans, depending on Cu intake, presence of other factors in the diet that may promote or inhibit its absorption and on the copper status of the individual. Current evidence suggests that copper deficiency may be more prevalent than previously thought, while copper toxicity is uncommon under customary daily life conditions. Menkes syndrome and Wilson disease are genetic conditions associated with severe copper deficiency and severe copper toxicity, respectively. Effects of milder degrees of copper deficiency and excess copper exposure are not well described, mainly due to lack of sensitive and specific indicators; serum copper concentration and ceruloplasmin are the most frequently used indicators, but they only detect rather intense changes of copper status. Of the many proteins assessed as potential markers of copper status the chaperone of Zn-Cu superoxide dismutase (CCS1) has yielded promising results; data on its performance under different conditions are needed to confirm its use as an indicator of early copper deficiency. Defining copper requirements and upper safe limits of consumption (UL) is a complex process since there are adverse health consequences from both copper deficiency and copper excess (U shape curve). The regulatory framework for risk assessment of essential trace elements introduced by the International Programme on Chemical Safety (IPCS) has proposed a homeostatic model to determine the Adequate Range of Oral Intake (AROI) of essential trace elements; the nadir of the resulting U shape curve serves to define the AROI. At this range of intake physiological mechanisms allow for normal homeostasis and basically, there are no detectable adverse effects. At present, Recommended Dietary Intakes (DRIs) and Adequate Intakes (AIs) are used to recommend copper intakes at different ages and life situations. Evidence obtained in humans and non-human primates presented here suggest that current copper UL should be re evaluated. Developing the scientific basis for a copper UL and evaluating the relevance of copper deficiency globally are future key challenges for copper researchers. Copyright © 2010 Elsevier GmbH. All rights reserved.",Biomarkers;Child;Copper/df [Deficiency];*Copper/ph [Physiology];Copper/to [Toxicity];*Homeostasis;Humans;0 (Biomarkers);789U1901C5 (Copper),"de Romana, D. L.;Olivares, M.;Uauy, R.;Araya, M.",2011,Jan,https://dx.doi.org/10.1016/j.jtemb.2010.11.004,0,0,
285,Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development,"BACKGROUND: zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies. MATERIALS AND METHODS: We identified a patient with Mowat-Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development. RESULTS: Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide-mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals. CONCLUSIONS: Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia.","Animals;Biliary Atresia/et [Etiology];Biliary Atresia/ge [Genetics];Biliary Atresia/me [Metabolism];Biliary Tract/ab [Abnormalities];*Biliary Tract/gd [Growth & Development];Facies;*Genes, Homeobox;Hepatocyte Nuclear Factor 1-beta/me [Metabolism];Hirschsprung Disease/co [Complications];*Hirschsprung Disease/ge [Genetics];Hirschsprung Disease/me [Metabolism];*Homeodomain Proteins/ge [Genetics];Homeodomain Proteins/me [Metabolism];Humans;Infant;Intellectual Disability/co [Complications];*Intellectual Disability/ge [Genetics];Intellectual Disability/me [Metabolism];Liver/me [Metabolism];Male;Microcephaly/co [Complications];*Microcephaly/ge [Genetics];Microcephaly/me [Metabolism];*Mutation;Oligoribonucleotides, Antisense/pd [Pharmacology];*Repressor Proteins/ge [Genetics];Repressor Proteins/me [Metabolism];Zebrafish;*Zinc Fingers;0 (HNF1B protein, human);0 (Homeodomain Proteins);0 (Oligoribonucleotides, Antisense);0 (Repressor Proteins);0 (ZEB2 protein, human);138674-15-4 (Hepatocyte Nuclear Factor 1-beta);Mowat-Wilson syndrome","Cui, S.;Erlichman, J.;Russo, P.;Haber, B. A.;Matthews, R. P.",2011,Mar,https://dx.doi.org/10.1097/MPG.0b013e3181ff2e5b,0,0,
286,"Penicillamine-induced elastosis perforans serpiginosa with abnormal ""lumpy-bumpy"" elastic fibers in lesional and non-lesional skin","Four types of elastosis perforans serpiginosa (EPS) have been described in literature: 1) idiopathic EPS, 2) reactive perforating elastosis associated with connective tissue disorders, 3) in some instances of pseudoxanthoma elasticum (PXE), disease-specific calcified elastic tissue is extruded, producing a clinical picture indistinguishable from other types, may also be seen in patients undergoing hemodialysis and 4) EPS induced by long-term treatment with D-penicillamine is observed in patients suffering from Wilson's disease. Long term D-penicillamine therapy causes an alteration in the dermal elastic tissue. D-penicillamine induced EPS has a distinctive histopathologic feature - serrated appearance of elastic fibers due to perpendicular budding from their surface giving a ""lumpy-bumpy"" look. D-penicillamine induced elastic fiber alteration may not always manifest clinically as EPS. We report a case of D-penicillamine induced widespread alteration in skin elastic tissue with distinct histopathologic features.","Adult;Biopsy, Needle;Elastic Tissue/de [Drug Effects];Elastic Tissue/pa [Pathology];Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Immunohistochemistry;Injections, Intralesional;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Rare Diseases;Severity of Illness Index;Skin Diseases/ci [Chemically Induced];Skin Diseases/dt [Drug Therapy];Skin Diseases/pa [Pathology];Treatment Outcome;Triamcinolone/ad [Administration & Dosage];1ZK20VI6TY (Triamcinolone);GNN1DV99GX (Penicillamine);Elastosis perforans serpiginosa","Khatu, S. S.;Dhurat, R. S.;Nayak, C. S.;Pereira, R. R.;Kagne, R. B.",2011,Jan-Feb,https://dx.doi.org/10.4103/0378-6323.74982,0,0,
287,Hepatocyte targeting and intracellular copper chelation by a thiol-containing glycocyclopeptide,"Metal overload plays an important role in several diseases or intoxications, like in Wilson's disease, a major genetic disorder of copper metabolism in humans. To efficiently and selectively decrease copper concentration in the liver that is highly damaged, chelators should be targeted at the hepatocytes. In the present work, we synthesized a molecule able to both lower intracellular copper, namely Cu(I), and target hepatocytes, combining within the same structure a chelating unit and a carbohydrate recognition element. A cyclodecapeptide scaffold displaying a controlled conformation with two independent faces was chosen to introduce both units. One face displays a cluster of carbohydrates to ensure an efficient recognition of the asialoglycoprotein receptors, expressed on the surface of hepatocytes. The second face is devoted to metal ion complexation thanks to the thiolate functions of two cysteine side-chains. To obtain a chelator that is active only once inside the cells, the two thiol functions were oxidized in a disulfide bridge to afford the glycopeptide P(3). Two simple cyclodecapeptides modeling the reduced and complexing form of P(3) in cells proved a high affinity for Cu(I) and a high selectivity with respect to Zn(II). As expected, P(3) becomes an efficient Cu(I) chelator in the presence of glutathione that mimics the intracellular reducing environment. Finally, cellular uptake and ability to lower intracellular copper were demonstrated in hepatic cell lines, in particular in WIF-B9, making P(3) a good candidate to fight copper overload in the liver.","Cells, Cultured;*Chelating Agents/ch [Chemistry];Chelating Agents/me [Metabolism];*Copper/ch [Chemistry];Copper/me [Metabolism];Hep G2 Cells;*Hepatocytes/ch [Chemistry];Hepatocytes/me [Metabolism];Humans;Molecular Structure;*Peptides, Cyclic/ch [Chemistry];Peptides, Cyclic/me [Metabolism];Peptides, Cyclic/pk [Pharmacokinetics];*Sulfhydryl Compounds/ch [Chemistry];Sulfhydryl Compounds/me [Metabolism];0 (Chelating Agents);0 (Peptides, Cyclic);0 (Sulfhydryl Compounds);789U1901C5 (Copper)","Pujol, A. M.;Cuillel, M.;Renaudet, O.;Lebrun, C.;Charbonnier, P.;Cassio, D.;Gateau, C.;Dumy, P.;Mintz, E.;Delangle, P.",2011,Jan 19,https://dx.doi.org/10.1021/ja106206z,0,0,
288,Evaluation of powder mixtures and hydrophilic gastroretentive drug delivery systems containing zinc acetate and sodium bicarbonate,"The aim of this study was to develop and study floating controlled drug delivery systems consisting of a model drug (zinc acetate dihydrate), different forms of a matrix-forming polymer (Metolose 90 SH) and sodium bicarbonate as an effervescent component. The proportions of Metolose and bicarbonate were varied, and the effects of the different ratios on the properties of the resulting powders and tablets were determined. The water uptakes of different powder mixtures were initially evaluated. These tests indicated the interaction of the active and effervescent agent, this phenomenon leading to an unpredicted increase in the amount of liquid taken up. This interaction was evaluated as concerns the degradation of the hydrophilic matrix system. The disintegration of tablets with different compositions revealed that this interaction increases the time required for the disintegration of these systems. The study demonstrated that the interaction of the components induced significant changes in the parameters of this new sensitive delivery system. In the last steps, the buoyancy and dissolution properties of tablets that appeared appropriate for the formulation of a controlled drug delivery system were investigated. Copyright © 2010 Elsevier B.V. All rights reserved.","Chemical Phenomena;Chemistry, Pharmaceutical;Delayed-Action Preparations/ad [Administration & Dosage];*Delayed-Action Preparations/ch [Chemistry];*Drug Delivery Systems/mt [Methods];*Excipients/ch [Chemistry];Gastric Juice/ch [Chemistry];Gastrointestinal Transit;Hepatolenticular Degeneration/dt [Drug Therapy];Hydrophobic and Hydrophilic Interactions;Hypromellose Derivatives;Kinetics;Methylcellulose/aa [Analogs & Derivatives];Methylcellulose/ch [Chemistry];Models, Chemical;Powders;*Sodium Bicarbonate/ch [Chemistry];Solubility;Tablets;Viscosity;Water/an [Analysis];Zinc Acetate/ad [Administration & Dosage];*Zinc Acetate/ch [Chemistry];Zinc Acetate/pk [Pharmacokinetics];0 (Delayed-Action Preparations);0 (Excipients);0 (Powders);0 (Tablets);059QF0KO0R (Water);3NXW29V3WO (Hypromellose Derivatives);8MDF5V39QO (Sodium Bicarbonate);9004-67-5 (Methylcellulose);FM5526K07A (Zinc Acetate)","Baki, G.;Bajdik, J.;Pintye-Hodi, K.",2011,Mar 25,https://dx.doi.org/10.1016/j.jpba.2010.10.026,0,0,
289,D-penicillamine interferes with S-homocysteinylation and S-cysteinylation of LDL apolipoprotein B,,*Apolipoproteins B/me [Metabolism];*Cysteine/me [Metabolism];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];*Homocysteine/me [Metabolism];Humans;Penicillamine/bl [Blood];*Penicillamine/me [Metabolism];Penicillamine/tu [Therapeutic Use];Sulfhydryl Compounds/bl [Blood];0 (Apolipoproteins B);0 (Sulfhydryl Compounds);0LVT1QZ0BA (Homocysteine);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Sotgia, S.;Carru, C.;Pinna, G. A.;Deiana, L.;Zinellu, A.",2011,Dec,https://dx.doi.org/10.1177/0091270010385933,0,0,
290,"Long-term follow-up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation","BACKGROUND AND AIMS: Wilson disease (WD) is an inherited disorder of copper metabolism. When treated, the outcome can be excellent, although the long-term survival has yet to be well documented. The aim of this study was to describe the long-term outcome of a cohort of patients with WD and to assess those factors affecting the phenotypic manifestation of WD. METHODS: The presence of mutations to the ATP7B gene, the clinical manifestations, treatments and the long-term outcomes were analysed retrospectively in 117 patients with WD (59 men and 58 women, aged at evaluation 38.5 +/- 11, range 16-63 years). RESULTS: Fifty-five patients with a neurological presentation, 51 patients with a hepatic presentation and 11 asymptomatic patients were followed up for an average of 15.1 +/- 10 years (median 12 years, range 1-41 years). The H1069Q ATP7B gene mutation was the most frequent genetic variant (54.3%); the frequency of this mutation did not differ between patients with either the hepatic or the neurological presentation (P = 0.099). d-penicillamine or zinc salts (81 and 17% respectively) were used for treatment, and three patients underwent liver transplantation. The majority of symptomatic patients became asymptomatic, or improved, during the follow-up (82% patients with hepatic presentation, 69% with neurological presentation). The long-term survival of patients with WD did not differ from that of the general Czech population (P = 0.95). CONCLUSIONS: Long-term follow-up shows a satisfactory response in the great majority of adequately treated patients with WD and survival coincides with that of the general population. Copyright © 2010 John Wiley & Sons A/S.",*Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Adolescent;Adult;Asymptomatic Diseases;*Cation Transport Proteins/ge [Genetics];Cation Transport Proteins/me [Metabolism];Chelating Agents/me [Metabolism];Chi-Square Distribution;*Copper/me [Metabolism];Czech Republic;DNA Mutational Analysis;Disease Progression;Female;Gene Frequency;Genetic Predisposition to Disease;Hepatolenticular Degeneration/en [Enzymology];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/mo [Mortality];Hepatolenticular Degeneration/th [Therapy];Humans;Kaplan-Meier Estimate;Liver Transplantation;Male;Middle Aged;*Mutation;Penicillamine/tu [Therapeutic Use];Phenotype;Retrospective Studies;Time Factors;Treatment Outcome;Young Adult;Zinc Acetate/tu [Therapeutic Use];Zinc Sulfate/tu [Therapeutic Use];0 (Cation Transport Proteins);0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine),"Bruha, R.;Marecek, Z.;Pospisilova, L.;Nevsimalova, S.;Vitek, L.;Martasek, P.;Nevoral, J.;Petrtyl, J.;Urbanek, P.;Jiraskova, A.;Ferenci, P.",2011,Jan,https://dx.doi.org/10.1111/j.1478-3231.2010.02354.x,1,1,
291,Extraordinary stability of copper(I)-tetrathiomolybdate complexes: possible implications for aquatic ecosystems,"An extraordinary affinity of MoS42- for Cu accounts for Mo-induced Cu deficiency in ruminants (molybdenosis) and offers an approach to treating Wilson's disease in humans. Evidence of thiomolybdates in sulfidic natural waters, and possibly even as metastable traces in oxic natural waters, raises the question of how Cu-Mo affinity might affect Cu availability or toxicity in aquatic ecosystems. Stabilities of inorganic Cu-MoS42- complexes are characterized and quantified here for the first time. Two remarkably stable Cu(I) dissolved complexes are identified (T=23degreeC +/- 2degreeC): Cu2(HS)2MoS42- and Cu2S2MoS44-. In addition, the solubility constant for a precipitate (NH4CuMoS4) was measured. Under the extremely reducing conditions in rumen fluids, these complexes will greatly suppress Cu(+) activity, supporting prior conclusions about the mechanism of molybdenosis. In sulfidic natural waters, they help to prevent complete Cu impoverishment, as might otherwise occur by sulfide mineral precipitation. On the other hand, the complexes discovered here are HS--dependent and could not be important in oxic natural waters (with HS- concentrations < 10-9 M) even if metastable, biogenic MoS42- indeed were present as previously conjectured. Copyright © 2010 SETAC.","Aquatic Organisms/de [Drug Effects];Aquatic Organisms/me [Metabolism];Complex Mixtures/ch [Chemistry];*Copper/ch [Chemistry];Copper/to [Toxicity];Ecosystem;Fresh Water/ch [Chemistry];Hydrogen-Ion Concentration;Models, Chemical;*Molybdenum/ch [Chemistry];Molybdenum/to [Toxicity];*Water Pollutants, Chemical/ch [Chemistry];Water Pollutants, Chemical/to [Toxicity];0 (Complex Mixtures);0 (Water Pollutants, Chemical);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Helz, G. R.;Erickson, B. E.",2011,Jan,https://dx.doi.org/10.1002/etc.379,0,0,
292,Orphan drugs. Dutch situation is similar,,*Astringents/ec [Economics];Drug Compounding;Drug Industry;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Netherlands;*Orphan Drug Production/ec [Economics];*Zinc Sulfate/ec [Economics];0 (Astringents);7733-02-0 (Zinc Sulfate),"Bouvy, M.",2010,Dec 07,https://dx.doi.org/10.1136/bmj.c7018,0,0,
293,"Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism","Wilson disease is an autosomal recessive disorder with copper metabolism. In Japan, the standard treatment is the administration of copper chelating agents, such as D-penicillamine and trientine. In this study, the authors used zinc acetate to treat Japanese patients with Wilson disease and investigated its efficacy. The 37 patients that comprise this study were found to have Wilson disease using clinical and biochemical tests and were administrated zinc acetate for 48 weeks. The authors followed the clinical symptoms and laboratory findings of the patients by assessing their complete blood counts, biochemical findings, as well as the results of urinalysis and special laboratory tests for copper and zinc metabolism. We also examined side effects of the treatment. Zinc acetate did not aggravate the hepatic or neurological symptoms of any of the patients. Blood biochemical analysis also did not reveal elevation of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltranspeptidase levels. Zinc treatment did not aggravate the patients' clinical signs and/or laboratory findings. However, it did improve some clinical symptoms of the Wilson disease patients. Although this agent had some side effects, none of them were severe. The authors measured spot urinary copper excretion, which gave an indication of the efficacy of treatment and of the sufficient dosage of zinc. We recommend maintaining a spot urinary copper excretion less than 0.075-mug/mg creatinine. The authors conclude that zinc acetate is an effective and safe treatment for Japanese patients with Wilson disease. Copyright © 2010 Mosby, Inc. All rights reserved.",Adolescent;Adult;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Blood Cell Count;Ceruloplasmin/de [Drug Effects];Ceruloplasmin/me [Metabolism];Child;*Copper/me [Metabolism];Copper/ur [Urine];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/ur [Urine];Humans;Japan;Liver/de [Drug Effects];Liver/me [Metabolism];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Zinc Acetate/ae [Adverse Effects];*Zinc Acetate/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine),"Shimizu, N.;Fujiwara, J.;Ohnishi, S.;Sato, M.;Kodama, H.;Kohsaka, T.;Inui, A.;Fujisawa, T.;Tamai, H.;Ida, S.;Itoh, S.;Ito, M.;Horiike, N.;Harada, M.;Yoshino, M.;Aoki, T.",2010,Dec,https://dx.doi.org/10.1016/j.trsl.2010.08.007,0,0,
294,Gabapentin as a rescue drug in D-penicillamine-induced status dystonicus in patients with Wilson disease,D-penicillamine induced status dystonicus is a unique but serious drug related complication in a subset of patients with Wilson disease. Patho-physiological basis of its occurrence is not known. It often responds poorly to anti dystonia medications. We present three patients with Wilson disease who developed severe paroxysmal dystonic spells after receiving D-penicillamine treatment. All three patients responded well to gabapentin after failing to respond to other anti dystonia drugs.,Adolescent;*Amines/tu [Therapeutic Use];*Anticonvulsants/tu [Therapeutic Use];Antidotes/ae [Adverse Effects];Child;*Cyclohexanecarboxylic Acids/tu [Therapeutic Use];Dystonic Disorders/ci [Chemically Induced];*Dystonic Disorders/dt [Drug Therapy];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/ae [Adverse Effects];*gamma-Aminobutyric Acid/tu [Therapeutic Use];0 (Amines);0 (Anticonvulsants);0 (Antidotes);0 (Cyclohexanecarboxylic Acids);56-12-2 (gamma-Aminobutyric Acid);6CW7F3G59X (gabapentin);GNN1DV99GX (Penicillamine),"Paliwal, V. K.;Gupta, P. K.;Pradhan, S.",2010,Sep-Oct,https://dx.doi.org/10.4103/0028-3886.72184,0,0,
295,Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease,"UNLABELLED: The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re-evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001. Forty children with WD (26 boys and 14 girls, age range = 1.1-20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD were evaluated. Both groups were symptom-free and had elevated aminotransferases as predominant signs of liver disease. In all WD patients, the diagnosis was supported by molecular analysis, the liver copper content, or both. A receiver operating characteristic (ROC) analysis of ceruloplasmin at the cutoff value of 20 mg/dL showed a sensitivity of 95% [95% confidence interval (CI) = 83%-99.4%] and a specificity of 84.5% (95% CI = 72.6%-92.6%). The optimal basal urinary copper diagnostic cutoff value was found to be 40 mug/24 hours (sensitivity = 78.9%, 95% CI = 62.7%-90.4%; specificity = 87.9%, 95% CI = 76.7%-95%). Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects, and the ROC analysis showed a sensitivity of only 12%. The WD scoring system was proved to have positive and negative predictive values of 93% and 91.6%, respectively. CONCLUSION: Urinary copper excretion greater than 40 mug/24 hours is suggestive of WD in asymptomatic children, whereas the penicillamine challenge test does not have a diagnostic role in this subset of patients. The WD scoring system provides good diagnostic accuracy. Copyright © 2010 American Association for the Study of Liver Diseases.","Adolescent;Ceruloplasmin/an [Analysis];Child;Child, Preschool;Copper/me [Metabolism];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ur [Urine];Humans;Infant;Liver/me [Metabolism];Liver Diseases/di [Diagnosis];Male;Penicillamine;Transaminases/bl [Blood];Young Adult;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1 (Transaminases);GNN1DV99GX (Penicillamine)","Nicastro, E.;Ranucci, G.;Vajro, P.;Vegnente, A.;Iorio, R.",2010,Dec,https://dx.doi.org/10.1002/hep.23910,0,0,
296,Wilson disease,"Wilson disease is an inherited autosomal recessive disorder of copper balance leading to hepatic damage and neurological disturbance of variable degree. The defective gene, ATP7B, encodes a hepatic copper-transporting protein, which plays a key role in human copper metabolism. Our knowledge of the genetic basis of Wilson disease has increased dramatically; however, understanding of genotype-phenotype correlation and multifarious effects of copper toxicity as basis for targeted and individualised therapy strategies is still insufficient. Clinical manifestations are related to copper accumulation predominantly in the liver and brain and include hepatic disease ranging from mild hepatitis to acute liver failure or cirrhosis and/or neurological symptoms such as dystonia, tremor, dysarthria, psychiatric disturbances. Mixed presentations occur frequently. Early recognition by means of clinical, biochemical or genetic examination and initiation of therapy with copper chelators, zinc salts or even liver transplantation in cases of acute and chronic liver failure are essential for favourable outcome. Copyright © 2010 Elsevier Ltd. All rights reserved.",Adenosine Triphosphatases/ge [Genetics];Algorithms;Cation Transport Proteins/ge [Genetics];Copper/me [Metabolism];Hepatocytes/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver Transplantation;0 (Cation Transport Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein),"Huster, D.",2010,Oct,https://dx.doi.org/10.1016/j.bpg.2010.07.014,0,0,
297,Zinc-induced copper deficiency in Wilson disease,,"Adult;Copper/bl [Blood];*Copper/df [Deficiency];Dose-Response Relationship, Drug;Evoked Potentials, Motor/de [Drug Effects];Follow-Up Studies;Glomerulonephritis/ci [Chemically Induced];Glomerulonephritis/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Long-Term Care;Male;Neurologic Examination/de [Drug Effects];*Polyneuropathies/ci [Chemically Induced];Zinc Sulfate/ad [Administration & Dosage];*Zinc Sulfate/to [Toxicity];Zinc Sulfate/ur [Urine];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper)","Horvath, J.;Beris, P.;Giostra, E.;Martin, P. Y.;Burkhard, P. R.",2010,Dec,https://dx.doi.org/10.1136/jnnp.2009.188896,0,0,
298,Partial status epilepticus induced by hypocupremia in a patient with Wilson's disease,"Although seizures are rarely encountered in Wilson's disease (WD), seizures related to hypocupremia have not been reported before. We report a patient presenting with partial status epilepticus who was on strict low-copper diet and chelating therapy for WD. Despite other rare causes of seizures in WD including penicillamine-induced pyridoxine deficiency, cerebral copper deposition and metabolic encephalopathy, the most probable cause of resistant status epilepticus in this patient was found as hypocupremia from overzealous treatment. This case exemplifies that hypocupremic states should be kept in mind as a risk factor for resistant seizures. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.","Brain/pa [Pathology];Brain/pp [Physiopathology];Copper/bl [Blood];*Copper/df [Deficiency];Electroencephalography;Epilepsies, Partial/bl [Blood];*Epilepsies, Partial/et [Etiology];Epilepsies, Partial/pp [Physiopathology];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Male;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Young Adult;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Benbir, G.;Gunduz, A.;Ertan, S.;Ozkara, C.",2010,Nov,https://dx.doi.org/10.1016/j.seizure.2010.07.018,0,0,
299,Synthesis and biological characterization of novel charge-deficient spermine analogues,"Biogenic polyamines, spermidine and spermine, are positively charged at physiological pH. They are present in all cells and essential for their growth and viability. Here we synthesized three novel derivatives of the isosteric charge-deficient spermine analogue 1,12-diamino-3,6,9-triazadodecane (SpmTrien, 5a) that are N(1)-Ac-SpmTrien (5c), N(12)-Ac-SpmTrien (5b), and N(1),N(12)-diethyl-1,12-diamino-3,6,9-triazadodecane (N(1),N(12)-Et(2)-SpmTrien, 5d). 5a and 5d readily accumulated in DU145 cells at the same concentration range as natural polyamines and moderately competed for the uptake with putrescine (1) but not with spermine (4a) or spermidine (2). 5a efficiently down-regulated ornithine decarboxylase and decreased polyamine levels, while 5d proved to be inefficient, compared with N(1),N(11)-diethylnorspermine (6). None of the tested analogues were substrates for human recombinant spermine oxidase, but those having free aminoterminus, including 1,8-diamino-3,6-diazaoctane (Trien, 3a), were acetylated by mouse recombinant spermidine/spermine N(1)-acetyltransferase. 5a was acetylated to 5c and 5b, and the latter was further metabolized by acetylpolyamine oxidase to 3a, a drug used to treat Wilson's disease. Thus, 5a is a bioactive precursor of 3a with enhanced bioavailability.","Acetyltransferases/ch [Chemistry];Acetyltransferases/ge [Genetics];Alternative Splicing/de [Drug Effects];Animals;Biogenic Polyamines/me [Metabolism];Cell Line, Tumor;Cell Proliferation/de [Drug Effects];Fibroblasts/de [Drug Effects];Fibroblasts/me [Metabolism];Humans;Kinetics;Mice;Oxidoreductases Acting on CH-NH Group Donors/ch [Chemistry];Recombinant Proteins/ch [Chemistry];*Spermine/aa [Analogs & Derivatives];Spermine/cs [Chemical Synthesis];Spermine/ch [Chemistry];Spermine/pd [Pharmacology];Structure-Activity Relationship;Substrate Specificity;0 (1,12-diamino-3,6,9-triazadodecane);0 (Biogenic Polyamines);0 (Recombinant Proteins);2FZ7Y3VOQX (Spermine);EC 1-5 (Oxidoreductases Acting on CH-NH Group Donors);EC 1-5-3 (polyamine oxidase);EC 2-3-1 (Acetyltransferases);EC 2-3-1-57 (diamine N-acetyltransferase)","Weisell, J.;Hyvonen, M. T.;Hakkinen, M. R.;Grigorenko, N. A.;Pietila, M.;Lampinen, A.;Kochetkov, S. N.;Alhonen, L.;Vepsalainen, J.;Keinanen, T. A.;Khomutov, A. R.",2010,Aug 12,https://dx.doi.org/10.1021/jm100439p,0,0,
300,Triethylenetetramine pharmacology and its clinical applications,"Triethylenetetramine (TETA), a Cu(II)-selective chelator, is commonly used for the treatment of Wilson's disease. Recently, it has been shown that TETA can be used in the treatment of cancer because it possesses telomerase inhibiting and anti-angiogenesis properties. Although TETA has been used in the treatment of Wilson's disease for decades, a comprehensive review on TETA pharmacology does not exist. TETA is poorly absorbed with a bioavailability of 8 to 30%. It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. It is mainly excreted in urine as the unchanged parent drug and two acetylated metabolites. It has a relatively short half-life (2 to 4 hours) in humans. The most recent discoveries in TETA pharmacology show that the major pharmacokinetic parameters are not associated with the acetylation phenotype of N-acetyltransferase 2, the traditionally regarded drug acetylation enzyme, and the TETA-metabolizing enzyme is actually spermidine/spermine acetyltransferase. This review also covers the current preclinical and clinical application of TETA. A much needed overview and up-to-date information on TETA pharmacology is provided for clinicians or cancer researchers who intend to embark on cancer clinical trials using TETA or its close structural analogs.",Animals;Chelating Agents/pd [Pharmacology];Chelating Agents/tu [Therapeutic Use];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Trientine/ch [Chemistry];*Trientine/pd [Pharmacology];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);SJ76Y07H5F (Trientine),"Lu, J.",2010,Sep,https://dx.doi.org/10.1158/1535-7163.MCT-10-0523,0,0,
301,Persistence with treatment in patients with Wilson disease,"BACKGROUND AND PURPOSE: Wilson disease is genetically induced failure of copper metabolism. If untreated, it may lead to death within several years from the onset of symptoms. Use of medication should therefore continue over the whole span of the patient's life after the diagnosis. Clinical observations show that patients with Wilson disease frequently stop the treatment. The aim of our study was to assess how drug compliance (defined as persistence with drug use) translates into the total well-being of patients with Wilson disease. MATERIAL AND METHODS: Patients diagnosed with Wilson disease and observed in our outpatient clinics were asked to fill in the self-completed questionnaire. Questions were related to demographic data, characteristics of the disease, methods of treatment and persistence with treatment, subjective assessment of health status and treatment efficacy. The EQ-5D questionnaire with a visual analogue scale of well-being was also used. RESULTS: Responses were obtained from 120 subjects but only 104 questionnaires could be further processed. Our analysis did not reveal differences in persistence with d-penicillamine and zinc sulphate use or efficacy of prescribed medication. We found, however, that regardless of the medication used, persistence with treatment resulted in significantly better results of self-assessment (total improvement in 39.7% vs. 7.7% in the non-persistent group, p = 0.003; partial improvement in 53.8% vs. 30.8%, respectively, p = 0.045; and deterioration: none in the persistent group vs. 42.3% in the non-persistent group, p < 0.0001). CONCLUSIONS: Lack of persistence with use of prescribed medication is rather frequent among patients with Wilson disease. Lack of compliance decreases chances for improvement and might be the cause of clinical deterioration.",*Chelating Agents/ad [Administration & Dosage];Drug Administration Schedule;Female;*Health Status;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Humans;Male;*Medication Adherence/sn [Statistics & Numerical Data];Patient Compliance/sn [Statistics & Numerical Data];Patient Satisfaction/sn [Statistics & Numerical Data];*Penicillamine/ad [Administration & Dosage];Poland;Quality of Life;Severity of Illness Index;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Maselbas, W.;Chabik, G.;Czlonkowska, A.",2010,May-Jun,,0,0,
302,[Follow-up study on the therapeutic efficacy in 80 children with Wilson disease],,"Adolescent;Child;Child, Preschool;Drug Therapy, Combination;Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];Zinc Sulfate/ad [Administration & Dosage];Zinc Sulfate/ae [Adverse Effects];7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine)","Xie, X. W.;Li, T.",2010,May,,0,0,
303,Rippled hyperpigmentation in Wilson's disease,,Biopsy;Chelating Agents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;*Hyperpigmentation/et [Etiology];Hyperpigmentation/me [Metabolism];*Hyperpigmentation/pa [Pathology];Melanins/me [Metabolism];Penicillamine/tu [Therapeutic Use];Skin/me [Metabolism];*Skin/pa [Pathology];Young Adult;0 (Chelating Agents);0 (Melanins);GNN1DV99GX (Penicillamine),"Al Mohizea, S.",2010,Jan,https://dx.doi.org/10.1111/j.1365-4632.2009.04150.x,0,0,
304,Adjunctive vitamin E treatment in Wilson disease and suggestions for future trials,,"*Antioxidants/tu [Therapeutic Use];Clinical Trials as Topic/mt [Methods];Drug Therapy, Combination;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Oxidative Stress/de [Drug Effects];Vitamin E/bl [Blood];*Vitamin E/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];0 (Antioxidants);1406-18-4 (Vitamin E);J41CSQ7QDS (Zinc)","Shen, L.;Ji, H. F.",2010,May,https://dx.doi.org/10.1002/hep.23665,0,0,
305,Mowat-Wilson syndrome: the first two Malaysian cases,"Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation; a multiple congenital anomaly syndrome characterised by a typical facial gestalt, Hirschsprung disease or severe constipation, genitourinary anomaly, congenital heart defects, agenesis of corpus callosum and eye defects. Some cases also present with epilepsy, growth retardation with microcephaly and speech impairment. MWS was first described in 1998 by Mowat et al, and approximately 180 cases have been reported as of August 2008. The syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). Most cases reported so far were sporadic occurrences; however, rare cases of sibling recurrence have been cited. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark, warranting ZEB2 mutational analysis even in the absence of Hirschsprung disease. We present the first two molecularly confirmed Malaysian MWS patients, one of whom has a novel mutation.","*Abnormalities, Multiple/di [Diagnosis];Abnormalities, Multiple/ge [Genetics];Child;Child, Preschool;Constipation;Epilepsy/ge [Genetics];Female;Gene Deletion;Hirschsprung Disease/ge [Genetics];Homeodomain Proteins/ge [Genetics];Humans;Malaysia;Repressor Proteins/ge [Genetics];0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Balasubramaniam, S.;Keng, W. T.;Ngu, L. H.;Michel, L. G.;Irina, G.",2010,Mar,,0,0,
306,Effect of glutathione depletion on removal of copper from LEC rat livers by tetrathiomolybdate,"Tetrathiomolybdate (TTM) is a powerful and selective copper (Cu) chelator that is used as a therapeutic agent for Wilson disease. TTM is the sole agent that can remove Cu bound to metallothionein (MT) in the livers of Long-Evans rats with a cinnamon-like coat color (LEC rats). However, the administration of excess TTM causes the deposition of Cu and molybdenum (Mo) in the liver. In the present study, the effect of hepatic glutathione (GSH) depletion on the removal of Cu from the livers of LEC rats was evaluated to establish an effective therapy by TTM. Pretreatment with l-buthionine sulfoximine (BSO), a depletor of GSH in vivo, reduced the amounts of Cu and Mo excreted into both the bile and the bloodstream, and increased the amounts of Cu and Mo deposited in the livers of LEC rats in the form of an insoluble complex 4h after the TTM injection. The results suggest that GSH depletion creates an oxidative environment in the livers of LEC rats, and the oxidative environment facilitates the insolubilization of Cu and Mo in the livers of LEC rats after the TTM injection. Therefore, the effect of TTM on the removal of Cu from the liver was reduced in the oxidized condition. Wilson disease patients and LEC rats develop liver injury caused by oxidative damage. From a clinical viewpoint, increasing in the GSH concentration is expected to enhance the effect of TTM. Copyright (c) 2010 Elsevier Inc. All rights reserved.","Animals;Buthionine Sulfoximine/ae [Adverse Effects];Buthionine Sulfoximine/pd [Pharmacology];Chelating Agents/ae [Adverse Effects];*Chelating Agents/pd [Pharmacology];*Copper/me [Metabolism];Enzyme Inhibitors/ae [Adverse Effects];Enzyme Inhibitors/pd [Pharmacology];*Glutathione/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;*Liver/me [Metabolism];Male;Metallothionein/me [Metabolism];Molybdenum/ae [Adverse Effects];Molybdenum/me [Metabolism];*Molybdenum/pd [Pharmacology];Oxidation-Reduction/de [Drug Effects];Rats;Rats, Inbred LEC;Rats, Wistar;Time Factors;0 (Chelating Agents);0 (Enzyme Inhibitors);5072-26-4 (Buthionine Sulfoximine);789U1901C5 (Copper);81AH48963U (Molybdenum);9038-94-2 (Metallothionein);91U3TGV99T (tetrathiomolybdate);GAN16C9B8O (Glutathione)","Ogra, Y.;Miyayama, T.;Anan, Y.",2010,Aug,https://dx.doi.org/10.1016/j.jinorgbio.2010.04.001,0,0,
307,Teaching NeuroImages: MRI reversal in Wilson disease with trientine treatment,,Adolescent;*Brain/pa [Pathology];*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Male;Treatment Outcome;Trientine/tu [Therapeutic Use];SJ76Y07H5F (Trientine),"Park, H. K.;Lee, J. H.;Lee, M. C.;Chung, S. J.",2010,Apr 27,https://dx.doi.org/10.1212/WNL.0b013e3181dad5cc,0,0,
308,Clinical features and therapeutic response in Taiwanese children with Wilson's disease: 12 years of experience in a single center,"BACKGROUND: Wilson's disease (WD) is an autosomal recessive defect of cellular copper export. Early diagnosis in children is difficult due to its obscure clinical presentations. The efficacy of zinc salts is well documented, although there are limited data concerning zinc use in pediatric patients with WD. METHODS: We performed a retrospective analysis of clinical features, laboratory results and treatment responses in children with WD diagnosed at Taichung Veterans General Hospital between 1996 and 2008. Diagnosis was established by low serum ceruloplasmin, high 24-hour urinary copper excretion, presence of Kayser-Fleischer rings, and mutation analysis. RESULTS: Eleven children were included in this study. The main initial presentations were impaired liver function tests (6/11) and hemolytic anemia (2/11). Gene studies in seven children showed six different mutations (G934D, R778Q, C490X, 304insC, IVS4-1 G > C, P992I) and one possible novel mutation (L1181P). All patients had improved liver function tests and hemoglobin levels after treatment with D-penicillamine, trientine and zinc supplement therapy. During a mean period of 3.4 +/- 2.1 years with zinc therapy, six patients had serum zinc levels above the normal limit, and seven patients had serum copper levels below the normal range. CONCLUSION: Serum ceruloplasmin and 24-hour urinary copper examinations could be used to rule out WD in children with chronic hepatitis and hemolytic anemia. Gene analysis is helpful for prompt diagnosis of asymptomatic siblings and patients with atypical features. Zinc treatment is generally safe in pediatric patients with WD. However, its adverse effects should be monitored. Copyright 2010 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.","Adolescent;Ceruloplasmin/an [Analysis];Child;Child, Preschool;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Liver Function Tests;Male;Retrospective Studies;Zinc/bl [Blood];Zinc Acetate/ad [Administration & Dosage];Zinc Acetate/tu [Therapeutic Use];EC 1-16-3-1 (Ceruloplasmin);FM5526K07A (Zinc Acetate);J41CSQ7QDS (Zinc)","Wang, L. C.;Wang, J. D.;Tsai, C. R.;Cheng, S. B.;Lin, C. C.",2010,Apr,https://dx.doi.org/10.1016/S1875-9572(10)60022-8,0,1,
309,Oral complications associated with D-penicillamine treatment for Wilson disease: a clinicopathologic report,"BACKGROUND: Wilson disease (WD) is a hereditary disease inhibiting copper release from the liver. Multi-organ manifestations involve the liver, nervous system, kidneys, eyes, heart, and skin. Elastic fiber damage is a complication of the most frequently used medication in the treatment of WD D-penicillamine (D-PCA). These changes have very rarely been described in the oral cavity. The article describes oral complications associated with WD and its treatment by D-PCA. METHODS: Clinical, radiographic, and microscopic evaluation was done on two WD female patients (aged 28 and 53), treated by D-PCA, with clinical and pathological evidence for oral drug-related complications. RESULTS: The lesions included multiple small red papules of the lips, gingival enlargement, early onset periodontitis, and repeated oral candidiasis. Biopsies of oral mucosa (gingiva, buccal) exhibited in one case granulomatous inflammation, and in both cases, thick irregular clumps of tortuous, red-staining abnormal elastic fibers. The red lip papules resemble elastosis perforans serpiginosa (EPS). Similar lesions have been described in the skin, but never before in association with oral or perioral tissue. In addition to the oral lesions, one of the patients developed general intolerance to the drug and was switched to trientine hydrochloride. CONCLUSIONS: WD patients and others treated by D-PCA may develop oral and perioral complications, in some cases exhibiting features of damaged elastic fibers in the mucosa and periodontal apparatus. It is possible that this damage may be one of the factors responsible for poor periodontal health in WD patients. Recognition of the lesions can lead to replacement of the affecting therapeutic agent.","Adult;Candidiasis, Oral/et [Etiology];Cheilitis/ci [Chemically Induced];*Chelating Agents/ae [Adverse Effects];Elastic Tissue/de [Drug Effects];Female;Follow-Up Studies;Gingival Hemorrhage/ci [Chemically Induced];Gingival Hyperplasia/ci [Chemically Induced];Gingival Recession/ci [Chemically Induced];Granuloma/ci [Chemically Induced];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lip Diseases/et [Etiology];Middle Aged;*Mouth Diseases/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Periodontal Pocket/ci [Chemically Induced];Periodontitis/ci [Chemically Induced];Tongue Diseases/ci [Chemically Induced];Tongue Diseases/mi [Microbiology];Trientine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Tovaru, S.;Parlatescu, I.;Dumitriu, A. S.;Bucur, A.;Kaplan, I.",2010,Aug,https://dx.doi.org/10.1902/jop.2010.090736,0,0,
310,Preparation of polyamine-functionalized copper specific adsorbents for selective adsorption of copper,"The level of serum free copper is greatly elevated in Wilson's disease. For patients with acute Wilson's disease, liver transplantation is the only lifesaving treatment. Plasma exchange or albumin dialysis is often used as a bridge to liver transplantation to maintain a stable clinical status for patients. Hemoperfusion is another effective therapy in removing toxins from the plasma. However, hemoperfusion has not been reported to remove copper due to lack of copper specific adsorbent. In this work, copper chelating agents, triethylenetetramine and tetraethylenepentamine, were covalently immobilized onto macroporous poly(glycidyl methacrylate-co-trimethylolpropane trimethacrylate) microspheres to prepare copper specific adsorbents. The resulting adsorbents demonstrated good adsorption capacities of 63.44 and 58.48 mg/g, respectively, for Cu2+ ion. Additionally, with the interference of other metal ions such as Fe2+, Mg2+, Zn2+ and Ca2+, the prepared copper adsorbents still demonstrated good specificity toward Cu2+ ion. These results indicate that the adsorbents are promising adsorbents in hemoperfusion therapy for selective removal of copper for patients with severe Wilson's disease. Copyright 2010 Elsevier B.V. All rights reserved.","Adsorption;Animals;Cattle;Chelating Agents/ch [Chemistry];*Copper/ch [Chemistry];Copper/pk [Pharmacokinetics];*Ethylenediamines/ch [Chemistry];Humans;Microscopy, Electron, Scanning;*Microspheres;Porosity;Serum Albumin/ch [Chemistry];Spectroscopy, Fourier Transform Infrared;Time Factors;*Trientine/ch [Chemistry];0 (Chelating Agents);0 (Ethylenediamines);0 (Serum Albumin);789U1901C5 (Copper);SJ76Y07H5F (Trientine);YZD1C9KQ28 (tetraethylenepentamine)","Yu, Z.;Wu, R.;Wu, M.;Zhao, L.;Li, R.;Zou, H.",2010,Jul 01,https://dx.doi.org/10.1016/j.colsurfb.2010.03.004,0,0,
311,Wilson disease: histopathological correlations with treatment on follow-up liver biopsies,"AIM: To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease (WD) patients. METHODS: We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies. Demographic, clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy. RESULTS: Time to repeat biopsy ranged from 2 to 12 years. Six patients (non-progressors) showed stable hepatic histology or improvement. In one case, we observed improvement of fibrosis from stage 2 to 0. Six patients (progressors) had worsening of fibrosis. There was no significant correlation between the histological findings and serum aminotransferases or copper metabolism parameters. The hepatic copper concentration reached normal levels in only two patients: one from the non-progressors and one from the progressors group. The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy (4 years), and 0.25 between the second and the third (3 years). In the progressors group, the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and, 0.6 fibrosis units between the second and third biopsy. CONCLUSION: The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered.",Adolescent;Adult;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Biomarkers/bl [Blood];Biopsy;*Chelating Agents/tu [Therapeutic Use];Child;*Copper/me [Metabolism];Copper/ur [Urine];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;*Liver/de [Drug Effects];Liver/me [Metabolism];Liver/pa [Pathology];*Liver Cirrhosis/dt [Drug Therapy];Liver Cirrhosis/et [Etiology];Liver Cirrhosis/me [Metabolism];Liver Cirrhosis/pa [Pathology];Male;*Penicillamine/tu [Therapeutic Use];Time Factors;Treatment Outcome;Young Adult;*Zinc Sulfate/tu [Therapeutic Use];0 (Biomarkers);0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine),"Cope-Yokoyama, S.;Finegold, M. J.;Sturniolo, G. C.;Kim, K.;Mescoli, C.;Rugge, M.;Medici, V.",2010,Mar 28,,1,1,
312,Copper deficiency myelopathy,"Acquired copper deficiency has been recognised as a rare cause of anaemia and neutropenia for over half a century. Copper deficiency myelopathy (CDM) was only described within the last decade, and represents a treatable cause of non-compressive myelopathy which closely mimics subacute combined degeneration due to vitamin B12 deficiency. Here, 55 case reports from the literature are reviewed regarding their demographics, aetiology, haematological and biochemical parameters, spinal imaging, treatment and outcome. The pathophysiology of disorders of copper metabolism is discussed. CDM most frequently presented in the fifth and sixth decades and was more common in women (F:M = 3.6:1). Risk factors included previous upper gastrointestinal surgery, zinc overload and malabsorption syndromes, all of which impair copper absorption in the upper gastrointestinal tract. No aetiology was established in 20% of cases. High zinc levels were detected in some cases not considered to have primary zinc overload, and in this situation the contribution of zinc to the copper deficiency state remained unclear. Cytopenias were found in 78%, particularly anaemia, and a myelodysplastic syndrome may have been falsely diagnosed in the past. Spinal MRI was abnormal in 47% and usually showed high T2 signal in the posterior cervical and thoracic cord. In a clinically compatible case, CDM may be suggested by the presence of one or more risk factors and/or cytopenias. Low serum copper and caeruloplasmin levels confirmed the diagnosis and, in contrast to Wilson's disease, urinary copper levels were typically low. Treatment comprised copper supplementation and modification of any risk factors, and led to haematological normalisation and neurological improvement or stabilisation. Since any neurological recovery was partial and case numbers of CDM will continue to rise with the growing use of bariatric gastrointestinal surgery, clinical vigilance will remain the key to minimising neurological sequelae. Recommendations for treatment and prevention are made. [References: 91]",*Copper/df [Deficiency];Humans;Spinal Cord Diseases/bl [Blood];*Spinal Cord Diseases/et [Etiology];Spinal Cord Diseases/pa [Pathology];Spinal Cord Diseases/th [Therapy];789U1901C5 (Copper),"Jaiser, S. R.;Winston, G. P.",2010,Jun,https://dx.doi.org/10.1007/s00415-010-5511-x,0,0,
313,Evaluation of Cuprimine and Syprine for decorporation of (60)Co and (210)Po,"The acknowledged risk of deliberate release of radionuclides into local environments by terrorist activities has prompted a drive to improve novel materials and methods for removing internally deposited radionuclides. These decorporation treatments will also benefit workers in the nuclear industry, should an exposure occur. Cuprimine and Syprine are oral therapeutics based on the active ingredients D-penicillamine and N,N'-bis-(2-aminoethyl)-1,2-ethanediamine dihydrochloride, respectively. These therapeutic drugs have been used for several decades to treat Wilson's disease, a genetic defect leading to copper overload, by chelation and accelerated excretion of internally deposited copper. Studies were undertaken to evaluate these FDA-approved drugs for the in vivo decorporation of radioactive cobalt (Co) and polonium (Po) using male Wistar-Han rats. In these studies, Co or Po was administered to animals by IV injection, followed by oral gavage doses of either Cuprimine or Syprine. Control animals received the radionuclide alone. For Co studies, animals received a single dose of Cuprimine or Syprine, while for Po studies animals were repeatedly dosed at 24-h intervals for a total of 5 doses. Results show that Syprine significantly increased urinary elimination and skeletal concentrations of Co compared to controls. While Cuprimine had little effect on total excretion of Co, the skeletal, kidney, liver, muscle, and stomach tissues had significantly lower radioactivity compared to control animals. The low overall excretion of Po made it difficult to reliably measure urinary or fecal radioactivity and draw a definitive conclusion on the effect of Cuprimine or Syprine treatment on excretion. However, Cuprimine treatment was effective at reducing spleen levels of Po compared to controls. Similarly, Syprine treatment produced statistically significant reductions of Po in the spleen and skeletal tissues compared to control animals. Based on these promising findings, further studies to evaluate the dose-response pharmacokinetic profiles for decorporation are warranted.","Animals;Chelating Agents/ad [Administration & Dosage];Chelating Agents/ch [Chemistry];Chelating Agents/pd [Pharmacology];Cobalt Radioisotopes/ch [Chemistry];*Cobalt Radioisotopes/ip [Isolation & Purification];Cobalt Radioisotopes/pk [Pharmacokinetics];Humans;Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/ch [Chemistry];*Penicillamine/pd [Pharmacology];*Polonium/ch [Chemistry];*Polonium/ip [Isolation & Purification];Polonium/pk [Pharmacokinetics];Rats;Rats, Wistar;Tissue Distribution;Trientine/ad [Administration & Dosage];*Trientine/ch [Chemistry];*Trientine/pd [Pharmacology];0 (Chelating Agents);0 (Cobalt Radioisotopes);DQY03U61EJ (Polonium);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Levitskaia, T. G.;Creim, J. A.;Curry, T. L.;Luders, T.;Morris, J. E.;Woodstock, A. D.;Levinson, B.;Thrall, K. D.",2010,Mar,https://dx.doi.org/10.1097/HP.0b013e3181bcdf4f,0,0,
314,Urinary copper/zinc ratio: a promising parameter for replacement of 24-hour urinary copper excretion for diagnosis of Wilson's disease in children,"BACKGROUND: Although 24-hour urinary copper excretion is valuable for diagnosis of Wilson's disease, accurate, timed collection entails practical difficulties. This study aimed to investigate the feasibility of morning urinary copper/creatinine or copper/zinc ratio as replacement parameter for diagnosing Wilson's disease. METHODS: Five random urinary samples collected during 24 hours from two inpatients were used to estimate the consistency of urinary copper/creatinine and copper/zinc ratios. The correlation of the ratios with 24-hour urinary copper excretion was studied in 15 patients with liver diseases. The diagnostic value of morning urinary copper/zinc ratio was further studied in 9 children with Wilson's disease and 22 children with other liver diseases. RESULTS: The coefficients of variation of urinary copper/creatinine and copper/zinc ratios during 24 hours were 12.5% and 9.3% respectively. The morning urinary copper/creatinine ratio, copper/zinc ratio, and 24-hour urinary copper excretion were correlated well. The area under receiver-operating characteristic curve was comparable between the morning urinary copper/zinc ratio and 24-hour urinary copper excretion (0.983 vs. 0.977). CONCLUSION: Morning urinary copper/zinc ratio seems to be a promising parameter in replacement of 24-hour urinary copper excretion for diagnosis of Wilson's disease.","Adolescent;Child;Child, Preschool;*Copper/ur [Urine];Creatinine/ur [Urine];Feasibility Studies;Female;*Hepatolenticular Degeneration/di [Diagnosis];Humans;Male;ROC Curve;Time Factors;*Zinc/ur [Urine];789U1901C5 (Copper);AYI8EX34EU (Creatinine);J41CSQ7QDS (Zinc)","Wang, J. S.;Lu, Y.;Wang, X. H.;Zhu, Q. R.",2010,May,https://dx.doi.org/10.1007/s12519-010-0023-4,0,0,
315,Wilson's disease: long-term follow-up of a cohort of 24 patients treated with D-penicillamine,"BACKGROUND AND STUDY AIMS: Detailed data on long-term effectiveness of various drug therapies in Wilson's disease (WD) are lacking. Therefore, we retrospectively reviewed our patient cohort treated with D-penicillamine. PATIENTS AND METHODS: This study reports on the clinical presentation, the diagnostic evaluation, and the disease course in 24 WD patients treated long-term (15+/-12 years, between 1969 and 2009) with D-penicillamine. RESULTS: The overall survival in our cohort was 91.6%. Twenty-two of 24 patients had liver disease at presentation, 17 of 24 patients (71%) had cirrhosis, 11 of whom had complications of cirrhosis. Six of 11 of these patients showed hepatological improvement (five of six) or stabilization (one of six), three of 11 were transplanted, one of 11 died, one of 11 discontinued follow-up. In the six of 17 cirrhotic patients without complications, improvement (four of six) or stabilization (two of six) occurred. Of all other patients (seven of 24), five of seven showed improvement (three of five) or stabilization (two of five), hepatological deterioration occurred only in one patient due to poor therapy compliance and one of seven discontinued follow-up. Neuropsychiatric symptoms were present in 13 of 24 at presentation and resolved in one of 13, decreased in seven of 13, stabilized in four of 13 and worsened in one of 13 patients (due to poor compliance). In general, we observed a favorable hepatological and neurological evolution with D-penicillamine. CONCLUSION: Despite the presence of liver disease or neuropsychiatric symptoms at baseline in all but one of the patients, we report beneficial results on liver and neurological disease after very long-term treatment with D-penicillamine, thereby adding to its reputation as 'first-line' therapy in WD.","Adolescent;Adult;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Carcinoma, Hepatocellular/co [Complications];*Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Child;Cohort Studies;Combined Modality Therapy;Female;Follow-Up Studies;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Diseases/dt [Drug Therapy];Liver Diseases/et [Etiology];Liver Diseases/su [Surgery];Liver Neoplasms/co [Complications];Liver Transplantation;Male;Nervous System Diseases/dt [Drug Therapy];Nervous System Diseases/et [Etiology];Patient Compliance;*Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];Retrospective Studies;Time Factors;Treatment Outcome;Young Adult;0 (Chelating Agents);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine)","Lowette, K. F.;Desmet, K.;Witters, P.;Laleman, W.;Verslype, C.;Nevens, F.;Fevery, J.;Cassiman, D. M.",2010,May,https://dx.doi.org/10.1097/MEG.0b013e3283353df8,0,0,
316,Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation,"Tetrathiomolybdate (TM) is an orally active agent for treatment of disorders of copper metabolism. Here we describe how TM inhibits proteins that regulate copper physiology. Crystallographic results reveal that the surprising stability of the drug complex with the metallochaperone Atx1 arises from formation of a sulfur-bridged copper-molybdenum cluster reminiscent of those found in molybdenum and iron sulfur proteins. Spectroscopic studies indicate that this cluster is stable in solution and corresponds to physiological clusters isolated from TM-treated Wilson's disease animal models. Finally, mechanistic studies show that the drug-metallochaperone inhibits metal transfer functions between copper-trafficking proteins. The results are consistent with a model wherein TM can directly and reversibly down-regulate copper delivery to secreted metalloenzymes and suggest that proteins involved in metal regulation might be fruitful drug targets.","*Carrier Proteins/ai [Antagonists & Inhibitors];Carrier Proteins/ch [Chemistry];*Carrier Proteins/me [Metabolism];Cation Transport Proteins/me [Metabolism];Chemical Phenomena;Copper/ch [Chemistry];*Copper/me [Metabolism];Crystallography, X-Ray;Ligands;*Metallochaperones/ai [Antagonists & Inhibitors];Metallochaperones/ch [Chemistry];*Metallochaperones/me [Metabolism];Models, Chemical;Models, Molecular;Molecular Structure;Molybdenum/ch [Chemistry];*Molybdenum/me [Metabolism];*Molybdenum/pd [Pharmacology];Oxidation-Reduction;Protein Conformation;*Saccharomyces cerevisiae Proteins/ai [Antagonists & Inhibitors];Saccharomyces cerevisiae Proteins/ch [Chemistry];*Saccharomyces cerevisiae Proteins/me [Metabolism];0 (ATX1 protein, S cerevisiae);0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Ligands);0 (Metallochaperones);0 (Saccharomyces cerevisiae Proteins);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 3-6-3-4 (CCC2 protein, S cerevisiae)","Alvarez, H. M.;Xue, Y.;Robinson, C. D.;Canalizo-Hernandez, M. A.;Marvin, R. G.;Kelly, R. A.;Mondragon, A.;Penner-Hahn, J. E.;O'Halloran, T. V.",2010,Jan 15,https://dx.doi.org/10.1126/science.1179907,0,0,
317,"Copper and zinc in the serum, urine, and hair of patients with Wilson's disease treated with penicillamine and zinc","The purpose of this study was to determine the different levels of copper and zinc in the serum, urine, and scalp hair of patients with Wilson's disease receiving different, currently accepted methods of treatment to reduce the copper load (penicillamine-group 1, n = 8; zinc-group 2, n = 8; penicillamine+zinc-group 3, n = 8). Blood, urine, and hair samples were collected from the patients. All three treatments resulted in a significant decrease of the serum copper levels. Significantly increased levels of zinc in the serum were detected in the patients in groups 2 and 3 (19.1 and 18.8 micromol/l, respectively; p < 0.05). Copper excretion in the urine significantly increased during its administration to groups 1 and 3 (11.5 and 7.94 micromol/24 h respectively; p < 0.001) due to the effect of penicillamine. The administration of zinc as monotherapy (group 2) or in combination with penicillamine (group 3) led to an increase of its excretion (25.3 and 22.4 micromol/24 h, respectively; p < 0.01). Only an insignificant rise of the copper content in the hair was found in all three groups of patients. The content of zinc in the hair did not differ significantly in any of the groups in comparison with the control group.",Adolescent;Adult;Case-Control Studies;Cohort Studies;*Copper/an [Analysis];*Copper/bl [Blood];*Copper/ur [Urine];Female;Hair/me [Metabolism];*Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ur [Urine];Humans;Male;Middle Aged;*Penicillamine/tu [Therapeutic Use];*Zinc/an [Analysis];*Zinc/bl [Blood];Zinc/tu [Therapeutic Use];*Zinc/ur [Urine];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Dastych, M.;Prochazkova, D.;Pokorny, A.;Zdrazil, L.",2010,Mar,https://dx.doi.org/10.1007/s12011-009-8438-2,0,1,
318,Zinc and tetrathiomolybdate for the treatment of Wilson's disease and the potential efficacy of anticopper therapy in a wide variety of diseases,"Wilson's disease, an autosomal recessive disease of copper accumulation and copper toxicity primarily in the liver and brain, has been the engine that has driven the development of anticopper drugs. Here we first briefly review Wilson's disease, then review the four anticopper drugs used to treat Wilson's disease. We then discuss the results of therapy with anticopper drugs in Wilson's disease, with special emphasis on the newer and better drugs, zinc and tetrathiomolybdate. We then discuss new areas of anticopper therapy, lowering copper availability with tetrathiomolybdate as a therapy in fibrotic, inflammatory, and autoimmune disorders. Many of the cytokines which promote these disorders are copper dependent, and lowering copper availability lessens the activity of these cytokines, favorably influencing a variety of disease processes. Copper in the blood can be thought of as in two pools. One pool is covalently bound in ceruloplasmin, a protein containing six coppers, synthesized by the liver and secreted into the blood. Ceruloplasmin copper accounts for almost 85 to 90% of the blood copper in normal people. This copper is tightly bound and not readily available for cellular uptake and copper toxicity. The other 10-15% of copper is more loosely bound to albumin and other small molecules in the blood, and is readily and freely available to cells and available to cause copper toxicity, if this pool of copper is increased. We call this latter pool of copper ""free"" copper because of its more ready availability. However, it should be understood that it is not completely free, always being bound to albumin and other molecules. It is this pool of free copper that is greatly expanded in untreated Wilson's patients undergoing copper toxicity.",Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];*Copper/ai [Antagonists & Inhibitors];Copper/bl [Blood];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/pd [Pharmacology];*Molybdenum/tu [Therapeutic Use];Zinc/pd [Pharmacology];*Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc),"Brewer, G. J.",2009,,https://dx.doi.org/10.1039/b901614g,0,0,
319,Impact of the discovery of human zinc deficiency on health,"The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment affects nearly 2 billion subjects in the developing world. High phytate content of the cereal proteins consumed in the developing world, results in decreased availability of zinc for absorption. Zinc therapy has been very successful and life saving measure in patients with acrodermatitis enteropathica and Wilson's disease. Beneficial therapeutic responses of zinc supplementation have been ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis, leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in decreasing incidences of infection in elderly and patients with sickle cell disease. Zinc supplementation was effective in preventing blindness in 25% of the elderly with dry type of age related macular degeneration. Zinc supplementation in the elderly decreased oxidative stress and decreased generation of inflammatory cytokines. Zinc is an intracellular signaling molecule in monocytes, dendritic cells and macrophages and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an anti-inflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress and increase generation of inflammatory cytokines. Oxidative stress and chronic inflammation may play important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and auto-immune diseases. It is therefore, important that status of zinc is assessed and zinc deficiency corrected in these chronic diseases. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is warranted. [References: 43]","Avitaminosis/hi [History];*Dietary Supplements;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/hi [History];History, 20th Century;History, 21st Century;Humans;*Zinc/df [Deficiency];Zinc/hi [History];Zinc/pd [Pharmacology];*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc)","Prasad, A. S.",2009,Jun,,0,0,112
320,Zinc: an essential micronutrient,"Zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression. Patients with malnutrition, alcoholism, inflammatory bowel disease, and malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of zinc deficiency are nonspecific, including growth retardation, diarrhea, alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in males. In developing countries, zinc supplementation may be effective for the prevention of upper respiratory infection and diarrhea, and as an adjunct treatment for diarrhea in malnourished children. Zinc in combination with antioxidants may be modestly effective in slowing the progression of intermediate and advanced age-related macular degeneration. Zinc is an effective treatment for Wilson disease. Current data do not support zinc supplementation as effective for upper respiratory infection, wound healing, or human immunodeficiency virus. Zinc is well tolerated at recommended dosages. Adverse effects of long-term high-dose zinc use include suppressed immunity, decreased high-density lipoprotein cholesterol levels, anemia, copper deficiency, and possible genitourinary complications. Copyright (c) 2009 American Academy of Family Physicians.",Humans;Micronutrients/ph [Physiology];*Micronutrients/tu [Therapeutic Use];Zinc/df [Deficiency];*Zinc/ph [Physiology];*Zinc/tu [Therapeutic Use];0 (Micronutrients);J41CSQ7QDS (Zinc),"Saper, R. B.;Rash, R.",2009,May 01,,0,0,
321,"Arthritis due to Wilson disease, penicillamine, psoriasis or hepatocellular carcinoma? Blurred focus, sharp boundaries",,"*Arthritis/et [Etiology];Carcinoma, Hepatocellular/co [Complications];Female;Hepatolenticular Degeneration/co [Complications];Humans;Liver Neoplasms/co [Complications];Middle Aged;Penicillamine/ae [Adverse Effects];Psoriasis/co [Complications];GNN1DV99GX (Penicillamine)","Emlakcioglu, E.;Ozcakar, L.;Kaymak, B.;Bayraktar, Y.;Akinci, A.",2009,Oct-Dec,,0,0,
322,Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin,"UNLABELLED: Wilson disease (WD) is an autosomal recessive copper overload disorder of the liver and basal ganglia. WD is caused by mutations in the gene encoding ATP7B, a protein localized to the trans-Golgi network that primarily facilitates hepatic copper excretion. Current treatment comprises reduction of circulating copper by zinc supplementation or copper chelation. Despite treatment, a significant number of patients have neurological deterioration. The aim of this study was to investigate the possibility that defects arising from some WD mutations are ameliorated by drug treatment aimed at improvement of protein folding and restoration of protein function. This necessitated systematic characterization of the molecular consequences of distinct ATP7B missense mutations associated with WD. With the exception of p.S1363F, all mutations tested (p.G85V, p.R778L, p.H1069Q, p.C1104F, p.V1262F, p.G1343V, and p.S1363F) resulted in reduced ATP7B protein expression, whereas messenger RNA abundance was unaffected. Retention of mutant ATP7B in the endoplasmic reticulum, increased protein expression, and normalization of localization after culturing cells at 30 degrees C, and homology modeling suggested that these proteins were misfolded. Four distinct mutations exhibited residual copper export capacity, whereas other mutations resulted in complete disruption of copper export by ATP7B. Treatment with pharmacological chaperones 4-phenylbutyrate (4-PBA) and curcumin, a clinically approved compound, partially restored protein expression of most ATP7B mutants. CONCLUSION: These findings might enable novel treatment strategies in WD by directly enhancing the protein expression of mutant ATP7B with residual copper export activity. 1795.).","Adaptor Proteins, Signal Transducing;Adenosine Triphosphatases/ch [Chemistry];*Adenosine Triphosphatases/ge [Genetics];Carrier Proteins/ch [Chemistry];Cation Transport Proteins/ch [Chemistry];*Cation Transport Proteins/ge [Genetics];Cell Line, Tumor;Copper/me [Metabolism];*Curcumin/pd [Pharmacology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Metallochaperones;Molecular Chaperones/ch [Chemistry];*Mutation;*Phenylbutyrates/pd [Pharmacology];Protein Conformation;*Protein Folding/de [Drug Effects];0 (ATOX1 protein, human);0 (Adaptor Proteins, Signal Transducing);0 (COMMD1 protein, human);0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Metallochaperones);0 (Molecular Chaperones);0 (Phenylbutyrates);789U1901C5 (Copper);7WY7YBI87E (4-phenylbutyric acid);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);IT942ZTH98 (Curcumin)","van den Berghe, P. V.;Stapelbroek, J. M.;Krieger, E.;de Bie, P.;van de Graaf, S. F.;de Groot, R. E.;van Beurden, E.;Spijker, E.;Houwen, R. H.;Berger, R.;Klomp, L. W.",2009,Dec,https://dx.doi.org/10.1002/hep.23209,0,0,
323,Wilson's disease: An Indian perspective,"Wilson's disease (WD) is an autosomal recessive disease involving a defect of copper transport by the hepatic lysosomes. It leads to excess copper deposition in the liver, the brain, the kidneys and the skeletal system, affecting most commonly children or young adults and running an invariably fatal course if not adequately treated by de-coppering therapy. The last century has witnessed several changes, notable among these are: Increased awareness, improved diagnostic facilities leading to earlier recognition even in the pre-symptomatic phase, clear distinction from its mimics, aggressive therapeutic approaches owing to availability of effective treatment and an overall reduction in the morbidity and mortality. It is widely acknowledged that the disease is not as rare as once believed. Sir SAK Wilson published his landmark article in 1912, but it was only in 1968 that the first patient of WD was reported from our country. Publications from India on WD have focused on phenotypic characterization, documentations of lesser recognized aspects of the disease e.g. seizures, behavior abnormality, speech and cognitive impairment, sub-clinical affection of visual pathway, heart and autonomic function and pre-symptomatic detection. Attempts have been made to understand the clinical heterogeneity of the disease through identification of biochemical and immunological markers, magnetic resonance imaging, neuropathological study and genetic analysis for novel and/or known mutations. Assessment of impairment and severity and effect of various therapeutic interventions namely zinc sulphate on the long-term outcome and quality of life have also been studied. Nevertheless, clinicians often face difficulties in long-term care of these patients. Diagnostic errors leading to delay in diagnosis and initiation of treatment are common, even in patients with positive family history. There is no consensus regarding therapeutic protocols since the use of penicillamine, once a 'gold standard' for treatment, has been debated by experts. Mortality and morbidity of this potentially treatable disease and nonavailability of medications to the poor patients remain a major area of concern.","Brain/pa [Pathology];*Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/hi [History];*Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration/pp [Physiopathology];History, 20th Century;History, 21st Century;Humans;India/ep [Epidemiology]","Taly, A. B.;Prashanth, L. K.;Sinha, S.",2009,Sep-Oct,https://dx.doi.org/10.4103/0028-3886.57789,0,0,
324,Zinc treatment for symptomatic Wilson disease: moving forward by looking back,,"Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Dose-Response Relationship, Drug;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Metallothionein/me [Metabolism];Penicillamine/tu [Therapeutic Use];Trace Elements/ae [Adverse Effects];*Trace Elements/tu [Therapeutic Use];Treatment Outcome;Zinc/ae [Adverse Effects];*Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);789U1901C5 (Copper);9038-94-2 (Metallothionein);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Schilsky, M.",2009,Nov,https://dx.doi.org/10.1002/hep.23355,0,0,
325,Mutational analysis for Wilson's disease,,"Adult;Alanine Transaminase/bl [Blood];Ceruloplasmin/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Copper/ur [Urine];DNA Mutational Analysis/mt [Methods];*DNA Mutational Analysis;Frameshift Mutation/ge [Genetics];Hepatitis B, Chronic/co [Complications];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Pedigree;Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine)","Seto, W. K.;Mak, C. M.;But, D.;Hung, I.;Lam, C. W.;Tam, S.;Yuen, M. F.;Lai, C. L.",2009,Aug 22,https://dx.doi.org/10.1016/S0140-6736(09)60915-6,0,0,
326,Wilson disease: current status and the future,"The focus of this minireview is on the current status and new advances in diagnosis and treatment of Wilson disease, an autosomal recessive disorder of copper metabolism. Molecular diagnostics have improved and complements current biochemical and clinical methods for screening for Wilson disease. Screening for Wilson disease in newborns is feasible and has been tested in limited populations, but is not yet widely performed. Identification of patients with Wilson disease as the cause of acute liver failure is possible using standard biochemical tests. Treatments for Wilson disease include chelating agents and zinc salts and liver transplantation. Future therapies may include hepatocyte transplantation and gene therapy, both of which have been tested and shown to work in animal models of Wilson disease. Future human studies await advances in these areas. [References: 27]",Adenosine Triphosphatases/ge [Genetics];Cation Transport Proteins/ge [Genetics];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/th [Therapy];Humans;0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein),"Schilsky, M. L.",2009,Oct,https://dx.doi.org/10.1016/j.biochi.2009.07.012,0,0,
327,Axonal sensory motor neuropathy in copper-deficient Wilson's disease,"Copper deficiency may cause myeloneuropathy or progressive limb weakness. By contrast, Wilson's disease (WD) is characterized by progressive copper accumulation with hepatic and neurological impairment and requires life-long treatment with zinc and/or chelator agents. We report a WD patient who developed axonal sensory motor neuropathy in the context of copper deficiency due to his treatment with zinc and chelators. Exhaustive testing for other etiologies was negative. After treatment adjustment, only mild clinical improvement was noted during long-term follow-up. Muscle Nerve 40: 294-296, 2009.",Adult;Axons/ph [Physiology];Chelating Agents/ae [Adverse Effects];*Copper/df [Deficiency];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Neural Conduction/ph [Physiology];Peripheral Nervous System Diseases/ci [Chemically Induced];*Peripheral Nervous System Diseases/me [Metabolism];Peripheral Nervous System Diseases/pa [Pathology];*Peripheral Nervous System Diseases/pp [Physiopathology];Zinc/ae [Adverse Effects];0 (Chelating Agents);789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Foubert-Samier, A.;Kazadi, A.;Rouanet, M.;Vital, A.;Lagueny, A.;Tison, F.;Meissner, W.",2009,Aug,https://dx.doi.org/10.1002/mus.21425,0,0,
328,Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine,"It has become clear that serum ""free"" copper (the copper not bound to ceruloplasmin in the blood) is the copper causing copper toxicity in Wilson's disease. But up until now, free copper has not been closely followed during initiation of anticopper therapy in neurologically presenting patients. During this period of initial therapy, the future fate of these patients hangs in the balance-if they worsen neurologically as often happens with penicillamine or trientine therapy, many never recover. We hypothesize that free copper levels are a biological marker of clinical outcome in these patients. In this article, we evaluate the control of free copper in 3 studies of initial anticopper treatment in neurologically presenting Wilson's disease patients. The first (study 1) is a 55-patient open-label trial of tetrathiomolybdate, the second (study 2) is a 48-patient double-blind trial comparing tetrathiomolybdate and trientine, and the third (study 3) is a 40-patient double-blind comparison of 2 disease regimens of tetrathiomolybdate. Free copper levels were determined by subtracting ceruloplasmin and tetrathiomolybdate bound copper from total serum copper. Tetrathiomolybdate showed very strong control of free copper levels over the 8 weeks of treatment in the 55-patient open-label study (study 1), reducing it to a mean value of about one fourth, or less, of baseline. In the tetrathiomolybdate/trientine double blind (study 2), tetrathiomolybdate again showed good control of free copper levels over 8 weeks of treatment, which is significantly better than trientine. In the trientine arm of study 2, mean free copper levels actually went up during trientine therapy. The 5 patients who neurologically worsened on trientine therapy over 8 weeks of treatment showed significant spikes in serum free copper levels associated in time with their neurologic worsening. Patients who did not worsen neurologically generally did not show significant spikes in free copper. Tetrathiomolybdate controlled copper less well in the dose regimen study (study 3) than in the previous 2 studies of tetrathiomolybdate treatment, probably because of a change in the way ""away from food"" tetrathiomolybdate was given.",Chelating Agents/ad [Administration & Dosage];*Chelating Agents/tu [Therapeutic Use];Clinical Trials as Topic;*Copper/bl [Blood];Double-Blind Method;Drug Administration Schedule;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/ad [Administration & Dosage];*Molybdenum/tu [Therapeutic Use];Retrospective Studies;Trientine/ad [Administration & Dosage];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);SJ76Y07H5F (Trientine),"Brewer, G. J.;Askari, F.;Dick, R. B.;Sitterly, J.;Fink, J. K.;Carlson, M.;Kluin, K. J.;Lorincz, M. T.",2009,Aug,https://dx.doi.org/10.1016/j.trsl.2009.05.002,0,0,
329,"""Acquired"" hepatocerebral degeneration in a patient heterozygote carrier for a novel mutation in ATP7B gene",,"*Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/ph [Physiology];Adult;Amino Acid Substitution;Basal Ganglia/pa [Pathology];*Cation Transport Proteins/ge [Genetics];Cation Transport Proteins/ph [Physiology];Copper/me [Metabolism];DNA Mutational Analysis;Exons/ge [Genetics];Genetic Predisposition to Disease;Hepatitis C, Chronic/co [Complications];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Heterozygote;Humans;Hydrophobic and Hydrophilic Interactions;Liver Cirrhosis/co [Complications];Male;Mutation, Missense;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Protein Structure, Secondary;Thrombocytopenia/ci [Chemically Induced];Trihexyphenidyl/tu [Therapeutic Use];0 (Cation Transport Proteins);6RC5V8B7PO (Trihexyphenidyl);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Cocco, G. A.;Loudianos, G.;Pes, G. M.;Tolu, F.;Lepori, M. B.;Barrocu, M.;Sechi, G. P.",2009,Aug 15,https://dx.doi.org/10.1002/mds.22659,0,0,
330,Status epilepticus in Wilson's disease,"RATIONALE: Seizures occur in Wilson's disease (WD), with prevalence figures as high as 4-6% in specialized academic centers, but status epilepticus is rare. We report a patient with WD who developed non-convulsive status epilepticus (SE) during therapy with Tetrathiomolybdate (TTM) and review the last 20 years of the relevant literature. CASE REPORT: A 55 year-old right handed man with WD who had parkinsonian features and hepatic cirrhosis was admitted for seizures. Seizures began on week 4 of treatment with TTM (Phase III Study of Tetrathiomolybdate Dose Regimen in Neurological Wilson's Disease). Seizures were characterized by forced clonic eye, head deviation to the right and right arm posturing followed by unresponsiveness, bilateral eye blinking and right hand automatisms. EEG confirmed frequent left frontal seizures. He developed non-convulsive status epilepticus (NCSE) with electrographic seizures every 5-10 minutes, lasting for 1-2 minutes each. Seizures were controlled within 24 hours with fosphenytoin, midazolam and levetiracetam. Brain MRI showed diffuse atrophy, mineralization of the basal ganglia, and patchy FLAIR increase signal in the left frontal lobe. LITERATURE REVIEW: We found reports of 6 WD patients with SE, two upon presentation of the disease and before copper removing treatment, and four after months to years of treatment with D-penicillamine. CONCLUSION: SE occurs rarely in WD, and our case is the only one reported to develop SE during treatment with TTM. As the literature documented two patients with WD who developed SE prior to copper deposit treatment, our hypothesis is that seizures in WD can be the result of the progression of the disease or a combination of factors but not necessarily due to its treatment alone.",Brain/pa [Pathology];*Brain/pp [Physiopathology];*Chelating Agents/tu [Therapeutic Use];Electroencephalography;Functional Laterality;*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Cirrhosis/co [Complications];Liver Cirrhosis/et [Etiology];Liver Cirrhosis/pp [Physiopathology];Magnetic Resonance Imaging;Male;Middle Aged;*Molybdenum/tu [Therapeutic Use];Review Literature as Topic;Seizures/et [Etiology];*Seizures/pp [Physiopathology];Status Epilepticus/et [Etiology];*Status Epilepticus/pp [Physiopathology];Treatment Outcome;0 (Chelating Agents);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Pestana Knight, E. M.;Gilman, S.;Selwa, L.",2009,Jun,https://dx.doi.org/10.1684/epd.2009.0254,0,0,
331,Long-term outcome in Serbian patients with Wilson disease,"BACKGROUND AND PURPOSE: To investigate survival rates, prognostic factors, and causes of death in Wilson disease (WD). METHODS: In the years 1980-2007, a cohort of 142 patients with WD was prospectively registered (54 presented with neurologic symptoms, 49 with hepatic symptoms, 33 had mixed form, and data were missing for six patients). The duration of follow-up for patients alive was 11.1 +/- 8.8 years. RESULTS: After initiation of treatment (d-penicillamine and zinc salts), 79% of patients had a stable or improved course of disease. Despite early diagnosis and appropriate therapy, 15 patients still had a relentlessly progressive course. Thirty patients died. The cumulative probability of survival in a 15-year period for the whole group was 76.7 +/- 4.9%. Better prognosis of WD was associated with male sex, younger age at onset, neurologic form of the disease, and treatment continuity. Causes of death were predominantly related to hepatic failure (16 patients), but also suicide (four patients) and cancer (three patients). CONCLUSION: Despite the relatively early diagnosis and treatment of our patients with WD, mortality was still considerably high.",Age of Onset;Cause of Death;Chelating Agents/tu [Therapeutic Use];Cohort Studies;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Penicillamine/tu [Therapeutic Use];Prognosis;Retrospective Studies;Serbia;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Svetel, M.;Pekmezovic, T.;Petrovic, I.;Tomic, A.;Kresojevic, N.;Jesic, R.;Kazic, S.;Raicevic, R.;Stefanovic, D.;Delibasic, N.;Zivanovic, D.;Dordevic, M.;Kostic, V. S.",2009,Jul,https://dx.doi.org/10.1111/j.1468-1331.2009.02607.x,1,1,
332,A 15-year-old girl with severe hemolytic Wilson's crisis recovered without transplantation after extracorporeal circulation with the Prometheus system,"BACKGROUND: Wilson's disease (WD) can present in a fulminant form with hepatocellular dysfunction, hemolysis and multiorgan failure (Wilson's crisis). We present a previously healthy young woman with severe WD whose WD severity score was 13. A score >11 indicates a poor chance of survival and liver transplantation will usually be recommended. METHODS: Penicillamine and acetylcysteine were initially administered, but the patient deteriorated further, and extracorporeal liver support with the Prometheus FPSA (fractionated plasma separation and adsorption) system was initiated. The patient was treated 6 h daily during 3 consecutive days. RESULTS: Severe hemolysis was reduced to low-grade hemolysis, with no further need for transfusions. The mental state improved and after 4 months practically all biochemical markers were normalized. CONCLUSIONS: This is the first report of FPSA albumin dialysis of a patient with Wilson's crisis and the first report in which a patient with a WD score >11 survived without transplantation.",Acetylcysteine/tu [Therapeutic Use];Adolescent;Antidotes/tu [Therapeutic Use];Copper/ip [Isolation & Purification];*Extracorporeal Circulation/is [Instrumentation];Female;Free Radical Scavengers/tu [Therapeutic Use];Hemolysis;*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/th [Therapy];Humans;*Liver/pp [Physiopathology];Penicillamine/tu [Therapeutic Use];Serum Albumin/me [Metabolism];Severity of Illness Index;0 (Antidotes);0 (Free Radical Scavengers);0 (Serum Albumin);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);WYQ7N0BPYC (Acetylcysteine),"Aagaard, N. K.;Thomsen, K. L.;Holland-Fischer, P.;Jorgensen, S. P.;Ott, P.",2009,,https://dx.doi.org/10.1159/000218090,0,0,
333,Education and imaging. Hepatobiliary and pancreatic: hypersensitivity pneumonitis induced by penicillamine,,"*Alveolitis, Extrinsic Allergic/ci [Chemically Induced];Alveolitis, Extrinsic Allergic/dg [Diagnostic Imaging];*Chelating Agents/ae [Adverse Effects];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Cirrhosis/dt [Drug Therapy];Liver Cirrhosis/et [Etiology];Middle Aged;*Penicillamine/ae [Adverse Effects];Radiography, Thoracic;Tomography, X-Ray Computed;Trientine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Seo, J. Y.;Kim, S. Y.;Choi, W. C.",2009,Apr,https://dx.doi.org/10.1111/j.1440-1746.2009.05819.x,0,0,
334,Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm,"BACKGROUND: Tetrathiomolybdate (TM) is a novel anticancer and anti-angiogenic agent, which acts through copper chelation and NF-kappaB inhibition. OBJECTIVE: This review summarizes the scientific rationale for the use of TM as an anticancer agent in human studies. METHODS: A systematic review of the literature was conducted for the use of TM in cancer including preclinical, animal and human studies. The results of this search are summarized in this review. RESULTS/CONCLUSIONS: Copper chelation using TM has demonstrated efficacy in preclinical and animal models as an alternative and novel anti-angiogenic agent. Phase I and II clinical trials conducted in solid tumors using TM have demonstrated efficacy with favorable toxicity profile. The use of copper lowering as an anti-angiogenic strategy in the cancer chemopreventative setting remains to be investigated. [References: 58]",Animals;Antineoplastic Agents/ae [Adverse Effects];Antineoplastic Agents/ch [Chemistry];Antineoplastic Agents/pk [Pharmacokinetics];*Antineoplastic Agents/tu [Therapeutic Use];Chelating Agents/ae [Adverse Effects];Chelating Agents/ch [Chemistry];Chelating Agents/pk [Pharmacokinetics];*Chelating Agents/tu [Therapeutic Use];*Copper/ai [Antagonists & Inhibitors];Copper/me [Metabolism];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/ae [Adverse Effects];Molybdenum/ch [Chemistry];Molybdenum/pk [Pharmacokinetics];*Molybdenum/tu [Therapeutic Use];Neoplasms/bs [Blood Supply];*Neoplasms/dt [Drug Therapy];*Neoplasms/me [Metabolism];0 (Antineoplastic Agents);0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Khan, G.;Merajver, S.",2009,Apr,https://dx.doi.org/10.1517/13543780902845622,0,0,
335,Improvement in dissolution of liver fibrosis in an animal model by tetrathiomolybdate,"The background for this study is that we have observed some improvement in cirrhosis in Wilson's disease patients treated with the anticopper medicine, zinc, and another anticopper drug, tetrathiomolybdate, has completely prevented hepatic fibrosis in the carbon tetrachloride mouse model. We hypothesize that in existing cirrhosis, there may be a fine balance between fibrosis formation and fibrosis dissolution, which may be pushed in the direction of dissolution by anticopper drugs. Thus, in this study, we produced hepatic fibrosis in mice by treatment with carbon tetrachloride, then gave half the fibrotic mice tetrathiomolybdate for 3 months, while the other half of the fibrotic mice received nothing for 3 months and served as controls. Tetrathiomolybdate caused a dramatic and significant reduction in fibrosis as measured by hydroxyproline (the major amino acid constituent of collagen) levels, almost back to baseline levels, compared to controls, who had only a slight and nonsignificant reduction. It is clear from this animal study that dissolution of preexisting fibrosis can be strongly catalyzed by lowering copper levels with tetrathiomolybdate. It now becomes important to evaluate whether this approach will work in the human epidemic of cirrhotic disease resulting from diseases such as alcoholism, nonalcoholic steatohepatitis, and hepatitis C.","Animals;Carbon Tetrachloride/to [Toxicity];Carbon Tetrachloride Poisoning/dt [Drug Therapy];Carbon Tetrachloride Poisoning/me [Metabolism];Carbon Tetrachloride Poisoning/pa [Pathology];*Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver Cirrhosis, Experimental/ci [Chemically Induced];*Liver Cirrhosis, Experimental/dt [Drug Therapy];Liver Cirrhosis, Experimental/me [Metabolism];Liver Cirrhosis, Experimental/pa [Pathology];Mice;Mice, Inbred BALB C;*Molybdenum/pd [Pharmacology];Molybdenum/tu [Therapeutic Use];Time Factors;789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);CL2T97X0V0 (Carbon Tetrachloride)","Hou, G.;Dick, R.;Brewer, G. J.",2009,Jun,https://dx.doi.org/10.3181/0811-RM-319,0,0,
336,Recurrent limb weakness in a 17-year-old boy,"Wilson disease is a relatively rare inherited disorder of copper accumulation and toxicity, caused by a defect in an enzyme that is part of the pathway of biliary excretion of excess copper. A 17-year-old boy presented with numerous episodes of hypokalemic weakness of the lower limbs of undetermined etiology since 12 years of age. Clinically, lower-motor neuron type of weakness of the limbs with preserved reflexes and paucity of sensory abnormalities were prominent. The investigations revealed distal renal tubular acidosis, hepatitis, and bilateral Kayser-Fleischer ring. The diagnosis of Wilson disease was confirmed by the demonstration of low serum ceruloplasmin, high serum copper, and high urinary copper excretion per se and after penicillamine challenge. He responded satisfactorily to penicillamine and zinc. Careful search of an underlying etiology in children presenting with hypokalemic weakness of the limbs in the face of metabolic acidosis and unexplained hepatitis may reveal Wilson disease.","Acidosis, Renal Tubular/di [Diagnosis];Acidosis, Renal Tubular/et [Etiology];Acidosis, Renal Tubular/th [Therapy];Adolescent;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Hypokalemia/di [Diagnosis];Hypokalemia/et [Etiology];Hypokalemia/th [Therapy];Leg;Male;*Muscle Weakness/et [Etiology];Recurrence","Thapa, R.;Biswas, B.;Mallick, D.",2009,Jun,https://dx.doi.org/10.1177/0009922809332684,0,0,
337,Wilson disease in children: analysis of 57 cases,"OBJECTIVES: Wilson disease (WD) has a wide spectrum of clinical manifestations. Affected children may be entirely asymptomatic and the diagnosis problematic. Herein we present the clinical and laboratory characteristics of 57 children with WD and point out the diagnostic difficulties in a pediatric population. PATIENTS AND METHODS: Clinical and laboratory data were collected from 57 consecutive children with WD. Evaluation included detailed physical examination, conventional laboratory testing, genetic analysis, and liver biopsy. RESULTS: The mean age at diagnosis was 9.27 +/- 3.62 years (range 4 months-18 years). Twenty patients were symptomatic, 19 were referred because of abnormal liver function test results and/or hepatomegaly, and 18 received their diagnoses after family screening. Twenty-two patients had both Kayser-Fleischer ring and decreased serum ceruloplasmin levels, 13 had urinary copper excretion after penicillamine challenge >1600 microg/24 hours, and 3 had liver copper content >250 microg/g dry weight. Of the remaining 19 patients, 17 had both low serum ceruloplasmin <or=20 mg/dL and increased urinary copper excretion, >75 microg/24 hours before, or >1000 microg/24 hours after penicillamine challenge. In 2 patients with equivocal cases who had serum ceruloplasmin 26 mg/dL, the diagnosis was confirmed by genetic analysis. No correlation was found between specific mutations and the disease phenotypic expression. Chelating therapy was well tolerated, and the outcome was satisfactory. CONCLUSIONS: WD in children may be obscure and requires extensive investigation to establish the diagnosis. Genetic analysis is needed in equivocal cases.","Adenosine Triphosphatases/ge [Genetics];Adolescent;Biopsy;Cation Transport Proteins/ge [Genetics];Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Copper/an [Analysis];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatomegaly;Humans;Infant;Liver/ch [Chemistry];Liver/pa [Pathology];Liver Function Tests;Male;Mutation;Penicillamine/tu [Therapeutic Use];0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Manolaki, N.;Nikolopoulou, G.;Daikos, G. L.;Panagiotakaki, E.;Tzetis, M.;Roma, E.;Kanavakis, E.;Syriopoulou, V. P.",2009,Jan,https://dx.doi.org/10.1097/MPG.0b013e31817d80b8,0,1,
338,Bullous pemphigoid induced by penicillamine in a patient with Wilson disease,"We report a 47-year-old man with Wilson disease who developed bullous lesions on the trunk and extremities after 20 years of penicillamine treatment. The histologic and immunofluorescence findings were diagnostic of bullous pemphigoid. When penicillamine was replaced by zinc sulfate, the patient's bullous skin lesions improved rapidly. However, after 2 months of zinc sulfate treatment, the patient's skin condition remained improved but his neurologic disease became worse and penicillamine was reinstituted. Bullous lesions recurred within 1 week and the diagnosis of penicillamine-induced bullous pemphigoid was confirmed. This is the first report of penicillamine-induced bullous pemphigoid in a patient with Wilson disease.","*Chelating Agents/ae [Adverse Effects];Diagnosis, Differential;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;*Pemphigoid, Bullous/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Popadic, S.;Skiljevic, D.;Medenica, L.",2009,,https://dx.doi.org/10.2165/0128071-200910010-00006,0,0,
339,The use of copper-lowering therapy with tetrathiomolybdate in medicine,"BACKGROUND: Tetrathiomolybdate (TM), an anticopper drug, has been developed for the neurologic presentation of Wilson's disease. In animal models, lowering copper levels with TM produces antifibrotic, anti-inflammatory, antiautoimmune, and anticancer effects, thought to be due to inhibition of many cytokines that are dependent on available copper for their activity. Clinical testing has been done relatively extensively in Wilson's disease and advanced cancers, but remains in its infancy in other diseases. OBJECTIVES: To review current preclinical and clinical studies done with TM, and our current knowledge of TM efficacy and toxicity. METHODS: We have reviewed the last 10 years of literature on TM therapy. RESULTS/CONCLUSION: TM has excellent efficacy and acceptable toxicity for the initial treatment of neurologically presenting Wilson's disease. TM has excellent efficacy in animal models of fibrotic, inflammatory, autoimmune, and neoplastic diseases, as well as Alzheimer's disease models. [References: 72]","Animals;Clinical Trials as Topic;*Copper/me [Metabolism];Disease;Drug Evaluation, Preclinical;Drug Tolerance;Humans;Molybdenum/ch [Chemistry];*Molybdenum/pd [Pharmacology];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Brewer, G. J.",2009,Jan,https://dx.doi.org/10.1517/13543780802621859,0,0,
340,Reactivity and kinetic studies of (NH4)2(MoS4) in acidic aqueous solution: possible relevance to the angiostatic function of the MoS4(2-) ligand,"Although addition of mineral acids to WS(4)(2-) in water is known to lead to aggregation and formation of various polynuclear thiotungstate anions, acid hydrolysis of the MoS(4)(2-) anion is reported to give mainly MoS(3) or MoS(2) as hydrolysis products. Knowledge of the resulting product(s) from such reactions has implications on the use of tetrathiomolybdate (MoS(4)(2-)) as both a potential anti-tumor drug and for the treatment of Wilson's disease. In this investigation, reaction of HCl with MoS(4)(2-) in water was monitored as a function of time. Reaction mixtures of both 1:1 and 2:1 mole ratios of the acid to MoS(4)(2-) were examined, as well as MoS(4)(2-) reactions in simulated human stomach fluids at pH of approximately 2 and 3. Monitoring by electrospray mass spectrometry (ESMS), Fourier transform infrared (FTIR), and UV-visible spectroscopy clearly has revealed the formation of complex mixtures of polynuclear thiomolybdates (Mo(2)-Mo(18)). Generally, a two-stage consecutive reaction sequence occurs. A faster stage (k=7.0-7.9 x 10(-2)min(-1)), which seems to extend to trinuclear thiomolybdate species, followed by a slower second stage (k=5.4-15.2 x 10(-4)min(-1)) to higher polynuclear thiomolybdates. Under acidic conditions (e.g. pH approximately 3) that could also mimic some human stomach fluids, and under anaerobic atmosphere where the generated hydrogen sulfide is prevented from escaping from the reaction vessel, Mo(3)S(9)(2-) predominates over an extended reaction period. In similar reactions under aerobic conditions and where the hydrogen sulfide is irretrievably lost from the reaction mixture the binuclear (Mo(2)O(a)S(10-a)(2-);a=0-3) and trinuclear (Mo(3)O(b)S(9-b)(2-);b=1-3) anions predominate.","*Angiogenesis Inhibitors/ch [Chemistry];Angiogenesis Inhibitors/pd [Pharmacology];Humans;Hydrochloric Acid/ch [Chemistry];Hydrochloric Acid/pd [Pharmacology];Kinetics;Ligands;*Molybdenum/ch [Chemistry];Molybdenum/pd [Pharmacology];Solutions/ch [Chemistry];Spectrometry, Mass, Electrospray Ionization;Water/ch [Chemistry];0 (Angiogenesis Inhibitors);0 (Ligands);0 (Solutions);059QF0KO0R (Water);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);QTT17582CB (Hydrochloric Acid)","Quagraine, E. K.;Georgakaki, I.;Coucouvanis, D.",2009,Jan,https://dx.doi.org/10.1016/j.jinorgbio.2008.09.015,0,0,
341,Hypothyroidism and dyshormonogenesis induced by D-penicillamine in children with Wilson's disease and healthy infants born to a mother with Wilson's disease,"Two siblings born to a mother with Wilson's disease, who was taking D-penicillamine, developed transient goitrous hypothyroidism. A prospective evaluation of 5 patients with Wilson's disease taking and not taking D-penicillamine for as long as 9.5 years showed subclinical hypothyroidism. D-penicillamine probably inhibited thyroperoxidase activity in utero in healthy infants and during childhood in patients with Wilson's disease.","Adolescent;*Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];Child;Female;*Goiter/ci [Chemically Induced];Goiter/dt [Drug Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Hypothyroidism/ci [Chemically Induced];Hypothyroidism/dt [Drug Therapy];Infant, Newborn;Male;Maternal-Fetal Exchange;*Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Pregnancy;Thyrotropin/bl [Blood];Thyroxine/tu [Therapeutic Use];0 (Chelating Agents);9002-71-5 (Thyrotropin);GNN1DV99GX (Penicillamine);Q51BO43MG4 (Thyroxine)","Hanukoglu, A.;Curiel, B.;Berkowitz, D.;Levine, A.;Sack, J.;Lorberboym, M.",2008,Dec,https://dx.doi.org/10.1016/j.jpeds.2008.06.015,0,0,
342,High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson's disease,"AIM: To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson's disease (WD) in Lithuania. METHODS: Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction (PCR) technique was used to detect the c.3207C>A (p.H1069Q) mutation. Patients not homozygous for the c.3207C>A (p.H1069Q) mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler (Biometra T3 Thermocycler, Gottingen, Germany). Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer (Applied Biosystems, Darmstadt, Germany). RESULTS: Total of 13 WD patients (mean age 26.4 years; range 17-40; male/female 3/10) presented with hepatic disorders and 16 their first degree relatives (including 12 siblings) were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders (hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2). Liver biopsy specimens were available in all of 13 WD patients (8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-liver steatosis). Twelve of 13 (92.3%) WD patients had the c.3207C>A (p.H1069Q) mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C>T (p.R1041W) or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder (Leipzig score 6), no mutations were found. Out of 16 first degree WD relatives, 11 (68.7%) were heterozygous for the c.3207C>A (p.H1069Q) mutation. Two patients with fulminant WD died from acute liver failure and 11 are in full remission under penicillamine or zinc acetate treatment. Three women with WD successfully delivered healthy babies. CONCLUSION: The c.3207C>A (p.H1069Q) missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.","*Adenosine Triphosphatases/ge [Genetics];Adolescent;Adult;*Cation Transport Proteins/ge [Genetics];Cohort Studies;DNA Mutational Analysis;*European Continental Ancestry Group/ge [Genetics];Exons;Female;Gene Frequency;Genetic Predisposition to Disease;Hepatolenticular Degeneration/eh [Ethnology];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];Heterozygote;Homozygote;Humans;Lithuania;Liver/pa [Pathology];Male;*Mutation, Missense;Pedigree;Phenotype;Young Adult;0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Kucinskas, L.;Jeroch, J.;Vitkauskiene, A.;Sakalauskas, R.;Petrenkiene, V.;Kucinskas, V.;Naginiene, R.;Schmidt, H.;Kupcinskas, L.",2008,Oct 14,,0,1,
343,The risks of free copper in the body and the development of useful anticopper drugs,"PURPOSE OF REVIEW: To review the toxicity and risks of free copper in Wilson's disease, Alzheimer's disease, other disease of neurodegeneration, and cognitive loss in the general population. We will also review the anticopper drugs and how lowering free copper levels with an anticopper drug inhibits fibrosis, inflammation, and autoimmunity. RECENT FINDINGS: Some exciting recent work indicates that free copper levels are increased in Alzheimer's disease, and copper may be involved in disease pathogenesis, opening the way to possible therapy of Alzheimer's disease with anticopper drugs. Copper may also be involved in other diseases of neurodegeneration. A very exciting recent study indicts high intake of copper, mostly from copper supplements, in conjunction with a high-fat diet in more rapid cognitive decline in the general population. Other data indicate that even low levels of copper in drinking water, perhaps similar to copper supplements, bypasses the liver, enters the circulation, increases the blood-brain penetration of copper, and may cause damage. SUMMARY: Some of the implications are that Alzheimer's disease and other diseases of neurodegeneration and fibrotic, inflammatory, and autoimmune diseases may be treatable by lowering the availability of free copper. People in the general population may wish to take steps to lower their free copper levels and, in particular, to abstain from taking copper supplements and ingesting significant amounts of copper in drinking water. [References: 51]",Alzheimer Disease/ci [Chemically Induced];Alzheimer Disease/dt [Drug Therapy];Alzheimer Disease/pc [Prevention & Control];Angiogenesis Inhibitors/tu [Therapeutic Use];Autoimmunity/de [Drug Effects];Autoimmunity/ph [Physiology];*Copper/ai [Antagonists & Inhibitors];*Copper/to [Toxicity];Fibrosis/me [Metabolism];Fibrosis/pc [Prevention & Control];Hepatolenticular Degeneration/ci [Chemically Induced];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Inflammation/me [Metabolism];Inflammation/pc [Prevention & Control];Molybdenum/tu [Therapeutic Use];*Neurodegenerative Diseases/ci [Chemically Induced];*Neurodegenerative Diseases/dt [Drug Therapy];Neurodegenerative Diseases/pc [Prevention & Control];Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];0 (Angiogenesis Inhibitors);789U1901C5 (Copper);81AH48963U (Molybdenum);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Brewer, G. J.",2008,Nov,https://dx.doi.org/10.1097/MCO.0b013e328314b678,0,0,
344,Haemolytic anaemia as a first sign of Wilson's disease,"A 19-year-old female presented with haemolytic anaemia and subsequently developed liver failure. This raised suspicion of Wilson's disease, which was confirmed by Kayser-Fleischer rings, a low ceruloplasmin level, raised 24-hour urinary copper excretion and two mutations in the 'Wilson gene'. She was successfully treated with D-penicillamine and zinc. In young patients with unexplained haemolysis, liver dysfunction or neuro-psychiatric symptoms, Wilson's disease should be considered.","Adult;*Anemia, Hemolytic/di [Diagnosis];Anemia, Hemolytic/dt [Drug Therapy];Anemia, Hemolytic/pp [Physiopathology];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;*Liver Failure/pp [Physiopathology]","Balkema, S.;Hamaker, M. E.;Visser, H. P.;Heine, G. D.;Beuers, U.",2008,Sep,,0,0,
345,Wilson's disease in Taiwan,"Wilson's disease (WD) has been studied in Taiwan since 1960s. The study can be divided into three periods: (1) The first period was 1960s, represented by the work of Dr. JB Tu who worked in the U.S. Naval Medical Research Unit No. 2 (NAMRU-2); (2) The second period was 1970s, represented by the work of Dr. ML Leu who also worked in NAMRU-2. During these two periods, d-penicillamine was introduced to Taiwan via NAMRU-2, primarily as study drug; and (3) The third period was 1980s and afterwards. Tu and Leu reported the clinical manifestations, tissue concentrations of copper, and therapeutic effects of d-penicillamine including cupriuresis, reduction of copper content in tissues, and prognosis. Our studies after 1980s included clinical manifestations, evoked potentials to detect the extent of CNS involvement, effect of superimposed hepatitis B infection on clinical manifestations and prognosis, and WD with cerebral white matter involvement. The present review highlights above investigations. [References: 54]",Brain/pa [Pathology];Hepatitis B/co [Complications];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Taiwan,"Chu, N. S.;Huang, C. C.",2008,Jun,,0,0,
346,"Tetrathiomolybdate, a copper chelator for the treatment of Wilson disease, pulmonary fibrosis and other indications","Tetrathiomolybdate (TTM) is a copper chelator that has also demonstrated antiangiogenic, antifibrogenic and anti-inflammatory actions in preclinical studies. The drug, from the University of Michigan was licensed to Pipex Pharmaceuticals Inc for development for several indications; development of the drug for cancer was later licensed to Attenuon LLC. In a phase III clinical trial, TTM stabilized neurological function in patients with Wilson disease, causing significant recovery in 81% of patients at 3 years post initiation of therapy; a second phase III trial was ongoing at the time of publication. A phase I/II clinical trial demonstrated the efficacy of TTM in patients with idiopathic pulmonary fibrosis, and led the FDA to grant TTM Orphan Drug status for this disease. Several phase II clinical trials had also been completed in patients with various cancers, and revealed mixed efficacy. TTM was also assessed in a phase I clinical trial for age-related macular degeneration, but the results reported from the trial were negative; no further development has occurred for this indication. TTM was assessed for the treatment of psoriasis in a phase II clinical trial, but no data have been reported. At the time of publication, phase II and phase III clinical trials were ongoing in patients with Alzheimer's disease and primary biliary cirrhosis, respectively. The most common clinical side effects observed for TTM over the range of indications have been anemia, neutropenia, leukopenia and transaminase elevations. These side effects were generally resolved with either a dose adjustment or temporary suspension of the dosing regimen. TTM is predicted to most likely find a niche in the therapy of Wilson disease, for which current treatment options are limited. [References: 83]","Angiogenesis Inhibitors/ad [Administration & Dosage];Angiogenesis Inhibitors/ae [Adverse Effects];Angiogenesis Inhibitors/pk [Pharmacokinetics];Animals;*Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Chelating Agents/pk [Pharmacokinetics];Clinical Trials as Topic;Drug Evaluation, Preclinical;Humans;*Molybdenum/ad [Administration & Dosage];Molybdenum/ae [Adverse Effects];Molybdenum/pk [Pharmacokinetics];Patents as Topic;United States;0 (Angiogenesis Inhibitors);0 (Chelating Agents);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Medici, V.;Sturniolo, G. C.",2008,Aug,,0,0,
347,Analysis of renal impairment in children with Wilson's disease,"BACKGROUND: Since the diverse manifestations of renal impairment appear in different periods of Wilson's disease, misdiagnosis or missed diagnosis is not rare. This study was undertaken to find the clinical features of renal impairment in children with Wilson's disease or hepatolenticular degeneration (HLD). METHODS: Eighty-five children with HLD who had been treated at our department between January 1991 and June 2006 were retrospectively studied. The clinical data of 25 patients with renal impairment were analyzed. RESULTS: In the 85 HLD patients, 34 had renal impairment. Nine of the 34 patients with D-penicillamine treatment were excluded. In the remaining 25 patients, 7 had initiated symptoms of renal impairment, 5 of them with edema, 1 with gross hematuria, and 1 with acute hemolysis and acute renal failure. Twelve of the 25 patients had proteinuria, 14 had hematuria, and 5 had both proteinuria and hematuria. Urine glucose was positive in 4 patients, urine N-acetyl-beta-D-glucosaminidase (NAG) increased in 5, and urine beta2-microglobulin increased in 6. Urine red blood cell (RBC) phase was detected in 7 patients, including glomerular hematuria in 5 patients and non-glomerular hematuria in 2. Blood urea nitrogen and creatinine increased in 1 patient. B-ultrasound revealed bilaterally enlarged kidneys in 3 patients. Kidney biopsy showed diffuse mesangial proliferation and IgA deposit in mesangial region in 1 patient. All of the 25 patients had cornea K-F ring and the level of ceruloplasmin decreased. Six patients had a family history of HLD. CONCLUSIONS: The manifestations of renal impairment with HLD are varied. HLD should be excluded from patients with unexplained renal impairment, while those with HLD should take examinations of the kidney to identify renal impairment. We propose that renal function and urinalysis should be checked regularly in patients receiving treatment of D-penicillamine.","Acetylglucosaminidase/ur [Urine];Acidosis, Renal Tubular/et [Etiology];Adolescent;Ceruloplasmin/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Child;Female;Glycosuria/et [Etiology];Hematuria/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Kidney Function Tests;Male;Penicillamine/tu [Therapeutic Use];Proteinuria/et [Etiology];*Renal Insufficiency/di [Diagnosis];Renal Insufficiency/et [Etiology];*Renal Insufficiency/pp [Physiopathology];Retrospective Studies;Urinalysis;0 (Chelating Agents);EC 1-16-3-1 (Ceruloplasmin);EC 3-2-1-52 (Acetylglucosaminidase);GNN1DV99GX (Penicillamine)","Zhuang, X. H.;Mo, Y.;Jiang, X. Y.;Chen, S. M.",2008,May,https://dx.doi.org/10.1007/s12519-008-0019-5,0,0,
348,Anesthesia for a patient with Wilson's disease--a case report,,"Amides;*Anesthesia;Anesthetics, Local;Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;Middle Aged;Nerve Block;Penicillamine/tu [Therapeutic Use];Rotator Cuff/su [Surgery];Rotator Cuff Injuries;0 (Amides);0 (Anesthetics, Local);0 (Chelating Agents);789U1901C5 (Copper);7IO5LYA57N (ropivacaine);GNN1DV99GX (Penicillamine)","De Souza Hobaika, A. B.",2008,Feb,,0,0,
349,Diagnosis of Wilson's disease: a comprehensive review,"Wilson's disease is an autosomal recessive disorder of copper metabolism. The culprit gene is ATP7B. The worldwide prevalence is about 1 in 30,000, which may vary by population. Higher prevalence rates were reported using more sensitive screening techniques and pilot population screening. Typical presentations include neuropsychiatric and hepatic dysfunction, whereas atypical presentations are protean. Diagnosis relies on a high clinical suspicion, typical neurological symptoms, presence of Kayser-Fleischer rings, and reduced serum ceruloplasmin concentration. The conventional value of < 0.20 g/l is not a universal diagnostic value. Age of the subjects and analytical variations should be considered when interpreting these levels. Patients with inconclusive findings require further investigations such as 24 h urinary free-copper excretion, penicillamine challenge test, liver copper measurement, and detection of gene mutations. Direct molecular diagnosis remains the most decisive tool. Other tests such as non-ceruloplasmin-bound copper are unreliable. Potential pitfalls and limitations of these diagnostic markers are critically reviewed in this paper. The mainstays of therapy are trientine, penicillamine, and/or zinc. Liver transplantation is lifesaving for those with advanced disease. Ceruloplasmin oxidase activity and serum free-copper concentration should be monitored in patients on long-term de-coppering therapy to prevent iatrogenic copper deficiency. [References: 198]","*Adenosine Triphosphatases/ge [Genetics];*Cation Transport Proteins/ge [Genetics];Ceruloplasmin/an [Analysis];Ceruloplasmin/df [Deficiency];Ceruloplasmin/me [Metabolism];Copper/bl [Blood];Copper/me [Metabolism];Copper/ur [Urine];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;*Mutation;Polymorphism, Single Nucleotide;0 (Cation Transport Proteins);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Mak, C. M.;Lam, C. W.",2008,,https://dx.doi.org/10.1080/10408360801991055,0,0,
350,Neurological deterioration during treatment in Wilson's disease: question,,Adult;*Antirheumatic Agents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;*Penicillamine/tu [Therapeutic Use];0 (Antirheumatic Agents);GNN1DV99GX (Penicillamine),"Kleinig, T. J.;Harley, H.;Thompson, P. D.",2008,May,,0,0,
351,MR spectroscopy in monitoring the treatment of Wilson's disease patients,"The aim of this study was to determine the effectiveness of brain proton magnetic resonance spectroscopy ((1)H-MRS) for monitoring therapy in Wilson's disease (WD) patients. Voxels were located in the globus pallidus (right, left). We followed 17 newly diagnosed WD cases for 1-year period. During this observation period, 6 neurological and 9 hepatic patients improved, while 2 neurological patients deteriorated. The pretreatment (1)H-MRS analysis showed a statistically significant lower level of mI/Cr, NAA/Cr, and higher Lip/Cr in all WD patients with improvement compared with controls. In patients with hepatic signs, a statistically significant increase of mI/Cr and Glx/Cr was observed in the second (1 year posttreatment) (1)H-MRS. In patients with neurological improvement after treatment in the follow-up (1)H-MRS, a statistically significant increase of NAA/Cr was noted. During neurological deterioration, a decrease of Glx/Cr and NAA/Cr was seen, in contrast to another neurologically impaired patient with liver failure exacerbation, where a decrease of mI/Cr and increase of Glx/Cr was observed. The alternations of NAA/Cr ratio in neurologically impaired patients and mI/Cr and Glx/Cr in patients with liver failure could be a sensitive marker of the clinical recovery and deterioration in those WD patients. (1)H-MRS is a technique that can be used for accurate monitoring of treatment efficacy in WD patients. Copyright (c) 2008 Movement Disorder Society.",Adolescent;Adult;Antidotes/tu [Therapeutic Use];Aspartic Acid/an [Analysis];Brain/me [Metabolism];Brain/pa [Pathology];Case-Control Studies;Choline/an [Analysis];Creatine/an [Analysis];Female;Follow-Up Studies;Glutamic Acid/an [Analysis];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Magnetic Resonance Imaging/mt [Methods];*Magnetic Resonance Spectroscopy/mt [Methods];Male;Penicillamine/tu [Therapeutic Use];*Protons;Severity of Illness Index;Young Adult;0 (Antidotes);0 (Protons);30KYC7MIAI (Aspartic Acid);3KX376GY7L (Glutamic Acid);GNN1DV99GX (Penicillamine);MU72812GK0 (Creatine);N91BDP6H0X (Choline),"Tarnacka, B.;Szeszkowski, W.;Golebiowski, M.;Czlonkowska, A.",2008,Aug 15,https://dx.doi.org/10.1002/mds.22163,0,0,
352,Usefulness of penicillamine-stimulated urinary copper excretion in the diagnosis of adult Wilson's disease,"OBJECTIVE: Diagnosis of Wilson's disease (WD) is reliant on liver biopsy (LB) and measurement of hepatic copper. The aim of this study was to determine the usefulness of penicillamine-stimulated urinary copper excretion (PS-UCE), a non-invasive diagnostic test, for the diagnosis of WD in adults. MATERIAL AND METHODS: In this prospective study of patients with suspected WD, total serum copper, ceruloplasmin, basal 24-h UCE and PS-UCE levels were measured. LB with copper determination was performed in those patients with persistent hypertransaminasemia and low ceruloplasmin or basal UCE > 40 microg/24 h. Diagnosis was established if the ceruloplasmin level was found to be < 20 mg/dl and hepatic copper > 250 microg/g. Results. A total of 115 patients were studied; LB was performed in 43, and WD was diagnosed in 6 (13.9%). Significant differences between WD and non-WD patients were found for basal UCE (WD: median 134.3 microg/24 h versus non-WD: median 19.0 microg/24 h (p < 0.05)) and PS-UCE (WD: median 1284.0 microg/24 h versus non-WD: median 776.0 microg/24 h; p < 0.01). In the ROC (receiver-operated curve) analysis, PS-UCE was the best discriminant between WD and non-WD (area under the curve (AUC) = 0.911, best cut-off point 1057 microg/24 h, 100% sensitivity, 82.3% specificity). CONCLUSIONS: PS-UCE is probably a useful non-invasive test in the diagnosis of WD, improving the selection of patients for diagnostic liver biopsy. Patients with PS-UCE under 1057 microg/24 h only rarely will suffer from WD and are unlikely to benefit from LB.","Adolescent;Adult;Biopsy, Needle;*Copper/ur [Urine];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/pa [Pathology];Male;*Penicillamine;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Foruny, J. R.;Boixeda, D.;Lopez-Sanroman, A.;Vazquez-Sequeiros, E.;Villafruela, M.;Vazquez-Romero, M.;Rodriguez-Gandia, M.;de Argila, C. M.;Camarero, C.;Milicua, J. M.",2008,,https://dx.doi.org/10.1080/00365520701847044,0,0,
353,Failure of prophylactic zinc in Wilson disease,"Early institution of prophylactic therapy of asymptomatic Wilson disease patients can prevent the expression of the disease. Zinc is currently preferred therapy for presymptomatic patients. We report onset of symptomatic disease in a presymptomatic patient and deterioration of biochemical parameters in another, despite appropriate zinc therapy.",Brain/pa [Pathology];Child;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Magnetic Resonance Imaging;Male;Treatment Failure;*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc),"Mishra, D.;Kalra, V.;Seth, R.",2008,Feb,,0,0,
354,Effect of trientine on manganese intoxication in a patient with acquired hepatocerebral degeneration,,Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Cognition Disorders/et [Etiology];Disease Progression;Hepatic Encephalopathy/co [Complications];*Hepatic Encephalopathy/di [Diagnosis];*Hepatic Encephalopathy/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Manganese/bl [Blood];Manganese Poisoning/co [Complications];*Manganese Poisoning/di [Diagnosis];*Manganese Poisoning/dt [Drug Therapy];Positron-Emission Tomography;Treatment Outcome;Tremor/et [Etiology];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);42Z2K6ZL8P (Manganese);SJ76Y07H5F (Trientine),"Park, H. K.;Kim, S. M.;Choi, C. G.;Lee, M. C.;Chung, S. J.",2008,Apr 15,https://dx.doi.org/10.1002/mds.21957,0,0,
355,Once daily trientine for maintenance therapy of Wilson disease,,Adult;Aged;Drug Administration Schedule;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Trientine/ad [Administration & Dosage];SJ76Y07H5F (Trientine),"Fox, A. N.;Schilsky, M.",2008,Feb,https://dx.doi.org/10.1111/j.1572-0241.2007.01646_15.x,0,0,
356,Wilson's disease: a clinico-neuropathological autopsy study,"Wilson's disease (WD), a familial neurological disorder involving the brain and liver secondary to altered copper metabolism, is common in South India. In view of the paucity of studies on this condition, the pathomorphological features of eight cases of WD were studied in detail at autopsy (brain alone, 1; brain and liver biopsy, 1; brain and visceral organs, 6), and are described with a discussion of the differential features of the neurological and hepatic forms. Of the six patients presenting with neurological manifestations, five had central pontine myelinolysis, five had subcortical white matter cavitations, four had putaminal softening, and six had variable ventricular dilatation, unlike the hepatic form. The presence of Opalski cells and pontine myelinolysis appear to be specific to the neurological form of WD. Liver abnormalities were observed in all cases (cirrhosis, 6; steatosis, 4; chronic active hepatitis, 2). Contrary to the rubric 'hepatolenticular degeneration', involvement of the lenticular nucleus was not universal, and nor was the pathology restricted to these anatomical areas.","Adolescent;Adult;Antigens, CD/me [Metabolism];Antigens, Differentiation, Myelomonocytic/me [Metabolism];Antirheumatic Agents/tu [Therapeutic Use];Autopsy/mt [Methods];*Brain/pa [Pathology];Child;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;India;*Liver/pa [Pathology];Male;Penicillamine/tu [Therapeutic Use];0 (Antigens, CD);0 (Antigens, Differentiation, Myelomonocytic);0 (Antirheumatic Agents);0 (CD68 antigen, human);GNN1DV99GX (Penicillamine)","Meenakshi-Sundaram, S.;Mahadevan, A.;Taly, A. B.;Arunodaya, G. R.;Swamy, H. S.;Shankar, S. K.",2008,Apr,https://dx.doi.org/10.1016/j.jocn.2006.07.017,0,0,
357,Cold comfort pharm,"In a difficult case when either the diagnosis remains elusive, or the treatment does not seem to work, sit down and carefully review all the records-a lesson from Wilson's disease. Practical issues to do with drug treatment may be just as important as its efficacy.",Adult;*Chelating Agents/tu [Therapeutic Use];*Cold Temperature;*Copper;Deglutition Disorders/et [Etiology];*Drug Storage;Dystonia/et [Etiology];Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;*Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);SJ76Y07H5F (Trientine),"Will, R. G.",2008,Feb,https://dx.doi.org/10.1136/jnnp.2007.139386,0,0,
358,Bone mineral density of children with Wilson disease: efficacy of penicillamine and zinc therapy,"OBJECTIVES: Osteoporosis accompanying chronic liver disease is well known; however, the exact prevalence is unknown. No data on bone mineral density (BMD) of children with Wilson disease (WD) have been published so far. In this study, we aimed to investigate the prevalence of osteoporosis in childhood WD and to observe the probable positive effects of penicillamine and zinc therapy on osteoporosis. METHODS: Thirty-one children with newly diagnosed WD and sex and age-matched 16 healthy children were included. Mean age was 9.0+/-3.2 years (2 to 16 y). Bone mineral content (BMC) and BMD were measured on admission and in 13 cases they were reassessed after 1 year of treatment with penicillamine and zinc. RESULTS: Mean BMD, BMC, and Z scores of the patients were significantly lower than those of healthy children: 0.52+/-0.09 versus 0.72+/-0.09 (P=0.001), 19.27+/-13.01 versus 29.67+/-14.23 (P=0.009), and -2.33+/-1.28 versus -0.12+/-0.31 (P=0.001), respectively. The prevalence of osteopenia and osteoporosis in children with WD was found as 22.6% and 67.7%, respectively. BMD and BMC levels were higher in children with neurologic involvement. The severity of the disease had no effect on the mentioned parameters. One year under treatment with penicillamine and zinc did not significantly alter the mentioned parameters. CONCLUSIONS: In this first study investigating the prevalence of osteoporosis in children with WD, we found an extremely high prevalence. Because of nonbeneficial effect of routine treatment of WD on osteoporosis, we emphasize the necessity of screening of bone mineralization and additional therapeutic approach for those children.","Adolescent;Bone Density/de [Drug Effects];*Bone Density;*Bone Diseases, Metabolic/co [Complications];Bone Diseases, Metabolic/dt [Drug Therapy];*Bone Diseases, Metabolic/ep [Epidemiology];Chelating Agents/pd [Pharmacology];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Female;*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Osteoporosis;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Prevalence;Trace Elements/pd [Pharmacology];Trace Elements/tu [Therapeutic Use];*Zinc/pd [Pharmacology];Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Trace Elements);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Selimoglu, M. A.;Ertekin, V.;Doneray, H.;Yildirim, M.",2008,Feb,https://dx.doi.org/10.1097/MCG.0b013e318032388d,0,0,
359,Neurological presentation of Wilson's disease in a patient after liver transplantation,"We report of a 32-year-old man who showed dystonic symptoms within few days after liver transplantation (LT). The clinical, biochemical, and, finally, genetic evaluation confirmed Wilson's disease diagnosis in this patient. We suspect that extrapyramidal signs in this case could be a result of acute brain injury because of the massive copper release from liver to the circulation just before and during LT. Copyright 2008 Movement Disorder Society",Adult;Copper/bl [Blood];Copper/ur [Urine];Disease Progression;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/et [Etiology];Humans;*Liver Transplantation/ae [Adverse Effects];Magnetic Resonance Imaging;Male;Pons/pa [Pathology];Remission Induction;Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper),"Litwin, T.;Gromadzka, G.;Czlonkowska, A.",2008,Apr 15,https://dx.doi.org/10.1002/mds.21913,0,0,
360,Dominant psychiatric manifestations in Wilson's disease: a diagnostic and therapeutic challenge!,"INTRODUCTION: Recognition of psychiatric manifestations of Wilson's disease (WD) has diagnostic and therapeutic implications. OBJECTIVE: To describe the clinical features and psychopathology of patients with WD who had initial or predominant psychiatric manifestations. PATIENT AND METHODS: Records of 15 patients with WD (M:F: 11:4), from a large cohort of 350 patients, with predominant psychiatric manifestations at onset were reviewed. Their initial diagnosis, demographic profile, family history, pre-morbid personality, clinical manifestations, treatment and outcome were recorded. RESULTS: Their mean age at diagnosis was 19.8+/-5.8 years. Six patients were born to consanguineous parentage and two patients each had family history of WD and past history of psychiatric illness. Diagnosis of WD was suspected by detection of KF rings (all), observing sensitivity to neuroleptics (n=2), history of jaundice (n=2) and family history suggestive of WD (n=9). Psychiatric manifestations could be classified as affective disorder spectrum (n=11) and schizophreniform-illness (n=3). While the psychiatric symptoms improved in five patients with de-coppering therapy, seven patients needed symptomatic treatment as well. Three of the four patients who responded to de-coppering therapy were sensitive to neuroleptics. Long-term follow up of 10 patients revealed variable recovery. CONCLUSIONS: Young patient with psychiatric manifestations with clues like history of jaundice, family history of neuropsychiatric manifestations and sensitivity to neuroleptics should be evaluated for WD to avoid delay in diagnosis and associated morbidity. SIGNIFICANT OUTCOMES: The study reemphasizes the importance of behavioral manifestations in Wilson disease in terms of diagnosis and management difficulties. LIMITATIONS: Retrospective nature of the study.",Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Cohort Studies;Copper/ai [Antagonists & Inhibitors];Copper/bl [Blood];Copper/ur [Urine];Depressive Disorder/et [Etiology];Depressive Disorder/px [Psychology];Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/px [Psychology];Hepatolenticular Degeneration/th [Therapy];Humans;Longitudinal Studies;Male;Mental Disorders/et [Etiology];*Mental Disorders/px [Psychology];Mood Disorders/et [Etiology];Mood Disorders/px [Psychology];Penicillamine/tu [Therapeutic Use];Psychotic Disorders/et [Etiology];Psychotic Disorders/px [Psychology];Schizophrenia/et [Etiology];Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Srinivas, K.;Sinha, S.;Taly, A. B.;Prashanth, L. K.;Arunodaya, G. R.;Janardhana Reddy, Y. C.;Khanna, S.",2008,Mar 15,https://dx.doi.org/10.1016/j.jns.2007.09.009,0,0,
361,"Withdrawal of penicillamine from zinc sulphate-penicillamine maintenance therapy in Wilson's disease: promising, safe and cheap","BACKGROUND: Penicillamine, once considered the cornerstone of treatment for Wilson disease (WD), is rather expensive and toxic, and often causes neurological worsening. Zinc sulphate, aiming at the treatment of free-copper toxicosis, has emerged as effective, safe and cheap alternative. AIM: To assess the effect of withdrawal of penicillamine from maintenance treatment with penicillamine and zinc sulphate. PATIENTS AND METHODS: 45 patients of WD (M:F: 28:17; age at diagnosis: 13.5+/-63 years), on both penicillamine (P) and zinc sulphate (Zn), couldn't continue penicillamine due to financial constraints. Their clinical data, disability and impairment scores (Schwab and England (S&E) score, Neurological Symptom Score (NSS), and Chu staging) and follow-up data of patients maintained only on zinc sulphate were recorded. RESULTS: Majority of patients (84.4%) had neuropsychiatric manifestations. The mean duration of treatment with penicillamine (P) and zinc sulphate (P+Zn), before stopping penicillamine, was 107.4+/-67.3 months. 40 patients improved variably, while the rest didn't. They received only zinc sulphate for 27.2+/-8.5 months (range: 12 to 34) and 44 patients (97.7%) remained status quo or improved marginally. Only one patient reported worsening in dysarthria. Their disability and impairment scores during combination (penicillamine and zinc sulphate) and Zn alone were: Chu (1.3+/-0.5 vs. 1.5+/-1.9; p=0.4), NSS (1.8+/-3.1 vs. 1.5+/-2.3; p=0.03) and S&E (96.4+/-5.6 vs. 98.6+/-3.5; p=0.03). There were no adverse effects. CONCLUSIONS: Withdrawal of penicillamine from zinc sulphate/penicillamine maintenance therapy for patients with Wilson's disease was effective, safe and economic, for almost all patients. This retrospective study reiterates that zinc sulphate may be used as a preferred mode of treatment for patients with Wilson's disease.","Adolescent;Adult;Astringents/ad [Administration & Dosage];Astringents/ec [Economics];Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Chelating Agents/ec [Economics];Chelation Therapy/ae [Adverse Effects];Chelation Therapy/ec [Economics];Chelation Therapy/mt [Methods];Child;Child, Preschool;Copper/me [Metabolism];Copper/to [Toxicity];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Neurocognitive Disorders/ci [Chemically Induced];Neurocognitive Disorders/me [Metabolism];Neurocognitive Disorders/pp [Physiopathology];*Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];Penicillamine/ec [Economics];Retrospective Studies;Treatment Outcome;*Zinc Sulfate/ad [Administration & Dosage];Zinc Sulfate/ec [Economics];0 (Astringents);0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Sinha, S.;Taly, A. B.",2008,Jan 15,https://dx.doi.org/10.1016/j.jns.2007.08.006,0,1,
362,Effect of penicillamine and zinc on iron metabolism in Wilson's disease,"OBJECTIVE: The physiology of iron metabolism in Wilson's disease is largely unknown, and there is a paucity of data on the real presence and progression of iron accumulation. The purpose of this study was to assess the iron metabolism parameters, including hepatic iron concentration, in follow-up liver biopsies and serum, and urinary pro-hepcidin. MATERIAL AND METHODS: Twenty-three Wilson's disease patients undergoing long-term treatment were enrolled in the study. RESULTS: Hepatic iron content was significantly increased in penicillamine-treated patients compared with zinc-treated patients. Serum and urinary pro-hepcidin concentrations were significantly higher in Wilson's disease patients than in healthy volunteers, despite a normal biochemical pattern of iron metabolism. CONCLUSIONS: Long-term penicillamine treatment seems to be responsible for a more marked iron accumulation in the liver. This observation may justify a revision of long-term Wilson's disease treatment modalities with penicillamine. The finding that serum and urinary pro-hepcidin is significantly increased in Wilson's disease patients compared with healthy volunteers suggests a role for hepcidin in iron metabolism in Wilson's disease, but this needs to be confirmed by a study of hepatic hepcidin expression in these patients.","Adolescent;Adult;Biopsy;*Chelating Agents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;*Iron/me [Metabolism];Male;Middle Aged;*Penicillamine/tu [Therapeutic Use];Statistics, Nonparametric;Treatment Outcome;*Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);E1UOL152H7 (Iron);GNN1DV99GX (Penicillamine)","Medici, V.;Di Leo, V.;Lamboglia, F.;Bowlus, C. L.;Tseng, S. C.;D'Inca, R.;Irato, P.;Burra, P.;Martines, D.;Sturniolo, G. C.",2007,Dec,https://dx.doi.org/10.1080/00365520701514495,0,1,
363,Mowat-Wilson syndrome,"Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical investigation with intervention of several specialists (including neonatologists and pediatricians). Psychomotor development is delayed in all patients, therefore rehabilitation (physical therapy, psychomotor and speech therapy) should be started as soon as possible. [References: 50]","*Abnormalities, Multiple/ge [Genetics];Adolescent;Adult;Child;Child, Preschool;Epilepsy/ge [Genetics];Female;Genotype;Hirschsprung Disease/ge [Genetics];*Homeodomain Proteins/ge [Genetics];Humans;Infant;Intellectual Disability/ge [Genetics];Male;*Maxillofacial Abnormalities/ge [Genetics];*Mutation/ge [Genetics];Phenotype;Prognosis;*Repressor Proteins/ge [Genetics];Syndrome;0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Garavelli, L.;Mainardi, P. C.",2007,Oct 24,https://dx.doi.org/10.1186/1750-1172-2-42,0,0,
364,D-Penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease,"Several drugs, including hydralazine and propylthiouracil, can induce antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. d-Penicillamine was implicated in a few patients with rheumatoid arthritis or systemic sclerosis, but in patients with both diseases, ANCA-associated vasculitides were described in the absence of the drug. Therefore, the role of d-penicillamine treatment could not be established. We report the first case of antimyeloperoxidase antibody-associated vasculitis in a patient treated with d-penicillamine for Wilson disease. Because Wilson disease was never associated with ANCA-related nephritis, this case strongly supports that d-penicillamine can induce ANCA-vasculitis. The presentation and rapidly progressive and potentially severe outcome of this complication dramatically contrast with those of membranous and minimal change glomerulopathy, also induced by the sulfhydryl compound.","Adult;*Antibodies, Antineutrophil Cytoplasmic/bl [Blood];*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Creatinine/bl [Blood];Disease Progression;Female;*Glomerulonephritis/ci [Chemically Induced];Glomerulonephritis/im [Immunology];Glomerulonephritis/pa [Pathology];Glucocorticoids/ad [Administration & Dosage];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Kidney Function Tests;Kidney Glomerulus/pa [Pathology];Methylprednisolone/ad [Administration & Dosage];Necrosis;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Peroxidase/im [Immunology];*Vasculitis/ci [Chemically Induced];Vasculitis/im [Immunology];0 (Antibodies, Antineutrophil Cytoplasmic);0 (Chelating Agents);0 (Glucocorticoids);AYI8EX34EU (Creatinine);EC 1-11-1-7 (Peroxidase);GNN1DV99GX (Penicillamine);X4W7ZR7023 (Methylprednisolone)","Bienaime, F.;Clerbaux, G.;Plaisier, E.;Mougenot, B.;Ronco, P.;Rougier, J. P.",2007,Nov,https://dx.doi.org/10.1053/j.ajkd.2007.05.026,0,0,
365,Central pontine signal changes in Wilson's disease: distinct MRI morphology and sequential changes with de-coppering therapy,"BACKGROUND AND PURPOSE: Reports of central pontine myelinolysis (CPM)-like changes in Wilson's disease (WD) and its sequential changes are exceptional. The aim was to study the MRI characteristics of CPM-like changes in WD and the serial changes. METHODS: Among the 121 patients of WD, twenty (M:F:9:11, age at onset: 14.2 +/- 4.6 years) had features similar to CPM. All had progressive neuropsychiatric form of WD. All except five were on de-coppering treatment. None had acute deterioration or hepatic failure. Ten patients underwent repeat studies. RESULTS: Twenty patients with CPM-like changes manifested with characteristic phenotype of WD. Three distinct patterns of CPM-like changes were observed: (a) characteristic round shape -7, (b) ""bisected"" -9, and (c) ""trisected"" -4. Only one had signal changes suggesting extra-pontine myelinolysis. All patients had contiguous involvement of midbrain. Serial MRI evaluation in 10 patients, at mean interval period of 17.4 +/- 13.2 months, revealed complete reversal in one, partial improvement in five, and no change in three. Clinical and MRI improvement occurred pari passu, except in one. CONCLUSIONS: CPM-like changes in WD are perhaps under-recognized and are distinct from the commonly known ""osmotic demyelination."" It is potentially reversible similar to other MRI features of WD.",Adolescent;Adult;Astringents/tu [Therapeutic Use];*Chelating Agents/tu [Therapeutic Use];Chi-Square Distribution;Child;Disease Progression;Female;Health Status Indicators;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;India;*Magnetic Resonance Imaging/mt [Methods];Male;Penicillamine/tu [Therapeutic Use];Phenotype;*Pons/pa [Pathology];Prognosis;Prospective Studies;Zinc Sulfate/tu [Therapeutic Use];0 (Astringents);0 (Chelating Agents);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine),"Sinha, S.;Taly, A. B.;Ravishankar, S.;Prashanth, L. K.;Vasudev, M. K.",2007,Oct,https://dx.doi.org/10.1111/j.1552-6569.2007.00120.x,0,0,
366,Significance of copper determination in late onset of Wilson's disease,"BACKGROUND: Wilson's disease is an autosomal recessive disorder of copper metabolism resulting from the dysfunction of a copper transporting P-type ATPase encoded on chromosome 13. When capacity for hepatic storage is exceeded, the excess copper manifests itself in toxic action. In this article, the case of a sudden unexpected death of a 22-year-old woman, as a result of a subclinical course of Wilson's disease, is reported. METHODS/RESULTS: A woman with no past medical history of underlying liver disease was hospitalized for nine days before death because of strong hemolytic anemia of unknown origin. Intoxication by lead, mercury, cadmium, thallium, zinc, chromium, manganese, and arsenic compounds was excluded. High levels of copper in blood and urine (AAS method) were found (blood: 3.90 microg/ml, urine: 8.10 microg/ml, 12,140 microg/24 h; normal - blood: 0.88 microg/ml, urine: 0.051 microg/ml, < 51 microg/24 h). Symptomatic treatment, aimed at multi-organ failure, was applied immediately. In spite of intensive care, the patient died. Post-mortem findings indicated the presence of anasacra and ascites, hydropericardium, brain edema, orange-like coloration of internal organs, and cirrhotic liver. Histopathological examination of liver slices revealed complete micro- and medionodular cirrhotic changes, focal central necrosis of the hepatocytes and cholestasis. The copper content in liver was 89.8 mug/g (normal: 3.58 +/- 1.71 microg/g). CONCLUSIONS: Assessment of tissue copper content is essential for the diagnosis of Wilson's disease in the living or after death (in living it can be helpful in proper diagnosis, and after death it enables one to ascertain the cause of a sudden death). The copper level in the liver in Wilson's disease is about 25 times higher than in the healthy liver.","Adult;*Copper/an [Analysis];Copper/bl [Blood];Copper/ur [Urine];Critical Care;Diagnosis, Differential;Fatal Outcome;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Liver/me [Metabolism];Liver/pa [Pathology];Middle Aged;Postmortem Changes;Time Factors;789U1901C5 (Copper)","Lech, T.;Hydzik, P.;Kosowski, B.",2007,Sep,https://dx.doi.org/10.1080/15563650701502535,0,0,
367,Cause of death in Wilson disease,"Before 1948, all patients with Wilson disease died shortly after diagnosis. In 1948, BAL (dimercaprol) was introduced as a possible effective treatment, to be followed by penicillamine (1955), zinc salts (1961), trientine (1969), liver transplantation (1982), and tetrathiomolybdate (1984). Despite this wide range of therapeutic options, patients still die. This article examines the cause of death in 67 patients (33 men, 34 women) out of a series of 300 seen between 1948 and 2000. Patients were classified according to their presentation as neurological, 32 patients, hepatic 11, mixed hepatic/neurological 10, hemolytic, 6, and ""sibling biopsy "" 8. Diagnostic failure was the principal cause of death but there were multiple other causes of which the principal was poor compliance and the development of malignant disease after 10 years of follow-up. The development of new symptoms should alert the physician to the possibility of a new pathology. Copyright (c) 2007 Movement Disorder Society.",Adolescent;Adult;Biopsy;Cause of Death;Ceruloplasmin/me [Metabolism];Child;Copper/bl [Blood];Female;Hemolysis;*Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/mo [Mortality];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver Diseases/me [Metabolism];*Liver Diseases/mo [Mortality];Liver Diseases/pa [Pathology];Male;Nervous System Diseases/me [Metabolism];*Nervous System Diseases/mo [Mortality];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin),"Walshe, J. M.",2007,Nov 15,https://dx.doi.org/10.1002/mds.21693,0,1,
368,Sequential MRI changes in Wilson's disease with de-coppering therapy: a study of 50 patients,"Wilson's disease (WD) is clinically and radiologically a dynamic disorder. However, there is a paucity of studies involving sequential MRI changes in this disease with or without therapy This study looked at serial MRI changes and their clinical correlate in patients with WD The severity of MRI changes using 1.5 T MRI in 50 patients with WD was graded based on alteration in signal intensity of focal lesions and atrophy. Details of clinical manifestations, Schwab and England Activities of daily living (MSEADL) score, Neurological Symptom Score (NSS) and Chu staging were recorded. Clinical severity and disability scores were correlated with MRI scores using SPSS v10 The mean age at onset of illness and diagnosis was 12.8+/-5.6 years and 14.4+/-6.0 years, respectively. At the time of first MRI, patients had been treated for 49.0+/-77.3 months. At a follow-up of 24.2+/-12.2 months, clinically 36 patients had improved, 9 remained the same and 5 had worsened. Serial imaging revealed an improvement in MRI parameters in 35 patients, no significant changes in 10, worsening in 4 and an admixture of resolving and evolving changes in 1. The overall MRI score improved from 8.2+/-5.7 to 5.9+/-6.6. There was an improvement in measures of disability and impairment in all: Chu stage, 11.5+/-0.7 to 1.3+/-0.6; MSEADL score (%), 79.7+/-27.6 to 88.0+/-25.4; NSS, 10.6+/-11.2 to 8.0+/-11.6, with good clinico-radiological correlation. Patients with extensive changes, white-matter involvement and severe diffuse atrophy had a poor prognosis In conclusion, the majority of patients with WD showed variable improvement in clinical and MRI features when treated.",Adolescent;Adult;Astringents/tu [Therapeutic Use];*Chelating Agents/tu [Therapeutic Use];Child;Disease Progression;Female;Health Status Indicators;*Hepatolenticular Degeneration/di [Diagnosis];Humans;India;Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];Prognosis;Prospective Studies;Zinc Sulfate/tu [Therapeutic Use];0 (Astringents);0 (Chelating Agents);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine),"Sinha, S.;Taly, A. B.;Prashanth, L. K.;Ravishankar, S.;Arunodaya, G. R.;Vasudev, M. K.",2007,Sep,https://dx.doi.org/10.1259/bjr/48911350,0,0,
369,"Validated, stability-indicated quantitative purity test for triethylenetetramine tetrachlorhydrate by automated multiple development","There is a monography of Triethylenetetramine dichlorhydrate (Trientine) in the United States Pharmacopeia. But neither the base nor the salts di- or tetra-chlorhydrate are in the European Pharmacopeia. Triethylene tetramine tetrachlorhydrate, used by AGEPS now as matural, is more soluble then triethylene tetramine dichlorhydrate. It is administred to patients with Wilson's disease, which results from a congenital lack of the copper metabolism. A quantitative purity test of this drug by automated multiple development high-performance thin-layer chromatography is developed and validated. The validation parameters tested are specifically characterized by retention factor, linearity, limits of detection and quantitation of several nanograms, reliability, and accuracy. To determine impurities, the monography of triethylenetetramine dichlorhydrate in the American Pharmacopeia is tested. This method in classic developing tank requires two mobile phases and is not quantitative. Assays in high-performance liquid chromatography with a different column and mobile phase did not give good results for the separation of impurities. Thus, it is not possible to perform comparative validation of the separation of the impurities. Only the assay of triethylenetetramine with potentiometer detection has been validated.",Reproducibility of Results;Sensitivity and Specificity;*Trientine/an [Analysis];SJ76Y07H5F (Trientine),"Dauphin, C.;Poirier, D.;Pradeau, D.",2007,Jul,,0,0,
370,Non-invasive testing for Wilson disease: revisiting the d-penicillamine challenge test,,*Chelating Agents;Copper/ur [Urine];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ur [Urine];Humans;*Penicillamine;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Schilsky, M. L.",2007,Aug,https://dx.doi.org/10.1016/j.jhep.2007.05.002,0,0,
371,"Hereditary iron and copper deposition: diagnostics, pathogenesis and therapeutics","Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about 200 times higher than the prevalence of Wilson's disease. The two diseases are characterized by homozygous occurrences of mutations in the HFE gene on chromosome 6 (primary haemochromatosis) and the ATP7B gene on chromosome 13 (Wilson's disease). Unlike most other inherited conditions, these diseases can be successfully treated, emphasizing the importance of early diagnosis. Serum ferritin values, transferrin saturation and genetic analysis are used when diagnosing haemochromatosis. The diagnostics of Wilson's disease depends on the use of urinary copper values, serum ceruloplasmin and liver biopsy. If untreated, both of these genetic diseases result in rapidly progressing multiorgan damage and early death. The key treatment for haemochromatosis is phlebotomy, for Wilson's disease chelation or Zn treatment. Although the present treatments considerably improve the prognosis of patients, they may be inadequate in patients diagnosed so late that extensive body deposits of metal have been developed. The main research needs in this field are to further clarify molecular mechanisms of disease progression and to develop new chelators that are more effective and less toxic than those presently available. [References: 81]","Adenosine Triphosphatases/ge [Genetics];Cation Transport Proteins/ge [Genetics];*Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];*Hemochromatosis/di [Diagnosis];Hemochromatosis/et [Etiology];Hemochromatosis/th [Therapy];Hemochromatosis Protein;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/et [Etiology];Hepatolenticular Degeneration/th [Therapy];Histocompatibility Antigens Class I/ge [Genetics];*Iron/me [Metabolism];Membrane Proteins/ge [Genetics];0 (Cation Transport Proteins);0 (Chelating Agents);0 (HFE protein, human);0 (Hemochromatosis Protein);0 (Histocompatibility Antigens Class I);0 (Membrane Proteins);789U1901C5 (Copper);E1UOL152H7 (Iron);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Aaseth, J.;Flaten, T. P.;Andersen, O.",2007,Jun,https://dx.doi.org/10.1080/00365520601075662,0,0,
372,Wilson disease in children: serum aminotransferases and urinary copper on triethylene tetramine dihydrochloride (trientine) treatment,"OBJECTIVES: To evaluate the efficacy of and adherence to trientine and/or zinc therapy in children with Wilson disease (WD). MATERIALS AND METHODS: We retrospectively reviewed the clinical records of all children with WD in the pediatric liver/liver transplant program at our institution between 1998 and 2006. RESULTS: A total of 22 children with WD were evaluated and treated. Seven with fulminant disease required liver transplantation and 15 were treated with trientine and/or zinc. Ten of those 15 had follow-up for 12 to 60 months and 6 of the latter 10 were followed for 12 to 18 months. All 10 patients were started on a trientine treatment regimen. Mean alanine aminotransferase (ALT) levels decreased from 183 +/- 103 IU at presentation (n = 10) to 80 +/- 46 IU at 12 months (n = 10) and 66 +/- 40 IU at 18 months (n = 7). Mean 24-hour urinary copper levels increased from 156 microg at presentation to 494 microg at 1 to 2 months, then decreased to 71 microg after 21 to 24 months of treatment. Three of 10 patients had normalized ALT levels and 1 patient with cirrhosis continued with normal ALT levels since presentation. Four of 10 patients were documented to be nonadherent, as manifested by increased ALT levels (99 +/- 31 IU); 1 patient had previously normalized ALT levels. In 3 of 10 patients, ALT level decreased but remained at an abnormal level (93 +/- 53 IU). CONCLUSIONS: Trientine and/or zinc therapy is effective for children with WD. Nonadherence is a common cause of increased aminotransferase levels in patients with WD.",Algorithms;*Chelating Agents/tu [Therapeutic Use];Child;*Copper/ur [Urine];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Patient Compliance;Retrospective Studies;*Transaminases/bl [Blood];Treatment Outcome;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);EC 2-6-1 (Transaminases);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Arnon, R.;Calderon, J. F.;Schilsky, M.;Emre, S.;Shneider, B. L.",2007,May,https://dx.doi.org/10.1097/MPG.0b013e3180467715,0,1,
373,Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson's disease in children,"BACKGROUNDS/AIMS: A urinary copper (Cu) >25 micromol/24 h following penicillamine had a reported specificity of 98.2% and sensitivity of 88.2% in diagnosing Wilson's disease (WD). We have re-evaluated this test. Ninety-eight subjects were studied at presentation. METHODS: Thirty-eight (19 girls, 19 boys; median age 10.3 years; range 5-16 years) had an ultimate diagnosis of WD. Sixty (24 girls, 36 boys; median age 10.1, range 2.3-15 years) had other liver disorders. Urinary Cu was estimated for 24h before (basal Cu) and for 24h whilst giving penicillamine 500 mg orally 12 hourly x 2 (post-penicillamine Cu). RESULTS: Both basal Cu and post-penicillamine Cu differed significantly between WD patients and controls (basal Cu: median 6.5 micromol/24 h, range 0.9-109 micromol/24 h, versus median: 0.8 micromol/24 h, range 0.1-19.5, p<0.0001; post-penicillamine Cu: median 36.9 micromol/24 h, range 1.98-219 micromol/24 h, versus median 12.35 micromol/24 h, range 0.5-49.8 micromol/24 h, p<0.0001). A post-penicillamine Cu >25 micromol/24 h was observed in 29/38 patients with WD and in 4/60 controls. 25/38 WD patients were symptomatic. Twenty-three of these and 6/13 asymptomatic siblings had a positive test. The test had a sensitivity of 76% (95% confidence interval [CI], 59.8-88.6%) and a specificity of 93% (95% CI, 83.8-98.2%). Sensitivity was better in symptomatic patients (92%, [95% CI; 74-99%]) than asymptomatic (46%, [95% CI; 19.2-74.9%]). CONCLUSIONS: This test is valuable in the diagnosis of WD with active liver disease, but is unreliable to exclude the diagnosis in asymptomatic siblings.","Adolescent;Ceruloplasmin/me [Metabolism];*Chelating Agents;Child;Child, Preschool;Circadian Rhythm;Copper/bl [Blood];Copper/me [Metabolism];Copper/ur [Urine];DNA Mutational Analysis;*Diagnostic Techniques, Digestive System/st [Standards];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/me [Metabolism];Liver/pa [Pathology];Male;*Penicillamine;Sensitivity and Specificity;0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Muller, T.;Koppikar, S.;Taylor, R. M.;Carragher, F.;Schlenck, B.;Heinz-Erian, P.;Kronenberg, F.;Ferenci, P.;Tanner, S.;Siebert, U.;Staudinger, R.;Mieli-Vergani, G.;Dhawan, A.",2007,Aug,https://dx.doi.org/10.1016/j.jhep.2007.03.011,0,0,
374,Wilson disease: description of 282 patients evaluated over 3 decades,"The clinical manifestations of Wilson disease (WD) are varied and challenging. We conducted the current study to present the phenotypic characteristics and follow-up for a large cohort of patients with WD. We reviewed the medical records of 282 cases of WD (male:female ratio, 196:86) for clinical features, investigations, treatment, and outcome data. The clinical presentations were as follows: hepatic, 42 (14.9%); hepato-neurologic, 10 (3.5%); neurologic, 195 (69.1%); pure psychiatric, 7 (2.4%); osseomuscular, 6 (2.1%); and ""presymptomatic,"" 15 (5.3%). Mean age was 15.9 years. Presymptomatic patients and those with the hepatic form of WD were younger and patients with osseomuscular and psychiatric forms were older than neurologic patients. The mean duration of illness at the time of diagnosis was 28 months. Predominant neurologic features were as follows: parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%; chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16%. Kayser-Fleischer (KF) rings were seen as follows: neurologic patients, 100%; hepatic patients, 86%; and presymptomatic patients, 59%. Positive family history was noted in 47% and consanguinity in 54%. Patients born of consanguineous parents had an earlier age of onset and shorter duration of illness before presentation. Serum ceruloplasmin was decreased in 93% and 24-hour urinary copper excretion was increased in 70% of patients. Neuroimaging (computed tomography/magnetic resonance imaging) and electrophysiologic abnormalities were seen in many patients. Overall, 195 patients were on D-penicillamine therapy and 182 on zinc sulphate. Follow-up data, available for 225 patients, for a mean duration of 46 months, revealed improvement in 176, no change in 20, and deterioration in 6. Twenty-three patients died. To conclude, despite increased awareness and recognition and significant inroads into therapeutic frontiers, follow-up remains poor in developing countries and a return to previous level of functioning is not universal.","Adolescent;Adult;Athetosis/et [Etiology];Brain/pa [Pathology];Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Chorea/et [Etiology];Cohort Studies;Consanguinity;Copper/ur [Urine];Dystonia/et [Etiology];Electroencephalography;Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/th [Therapy];Humans;India/ep [Epidemiology];Magnetic Resonance Imaging;Male;Middle Aged;Myoclonus/et [Etiology];*Outcome Assessment (Health Care);Parkinsonian Disorders/et [Etiology];Penicillamine/tu [Therapeutic Use];Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Taly, A. B.;Meenakshi-Sundaram, S.;Sinha, S.;Swamy, H. S.;Arunodaya, G. R.",2007,Mar,https://dx.doi.org/10.1097/MD.0b013e318045a00e,0,1,
375,Wilson's disease,,"*Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Drug Administration Schedule;Drug Interactions;Drug Therapy, Combination;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];*Trientine/ad [Administration & Dosage];Trientine/ae [Adverse Effects];Zinc/ad [Administration & Dosage];0 (Chelating Agents);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Walshe, J. M.",2007,Mar 17,https://dx.doi.org/10.1016/S0140-6736(07)60438-3,0,0,
376,Wilson's disease with hepatic presentation in childhood,"Diagnosis of Wilson's disease with hepatic presentation in childhood using clinical and common laboratory parameters is still challenging and is often missed or delayed. The aim of the study was to document the clinical and laboratory parameters of hepatic presentation of Wilson's disease in children. The study was conducted at a tertiary-care hospital in a developing country. Clinical and common laboratory parameters were recorded in 32 Wilson's disease children with hepatic presentation. The diagnosis was based on positive family history, Kayser-Fleischer ring, low serum ceruloplasmin level, elevated basal urinary copper excretion and favorable response to therapy with D-penicillamine. Mean age+/-SD at presentation was 9+/-2.97 years and 21 (65.6%) were boys. Chronic liver disease (21; 65.6%) followed by fulminant hepatic failure 1(6; 18.8%) were the commonest presentation. In the whole group, Kayser-Fleischer ring was found in 21 (65.6%), low serum ceruloplasmin in 16 (50%) and elevated basal urinary copper excretion in all 32 (100%) children. Diagnosis of Wilson's disease was made at presentation on the basis of i) Kayser-Fleischer ring, low serum ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 11 (34.4%), ii) Kayser-Fleischer ring, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 10 (31.2%), iii) elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 6 (18.8%) and iv) low ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 5 (15.6%) children. Wilson's disease can not be excluded in children presenting with hepatic involvement using the commonly practiced clinical and laboratory parameters. A combination of various clinical and laboratory parameters were used for the diagnosis of Wilson's disease in the studied children with hepatic presentation.","Adolescent;Age Factors;Bangladesh;*Ceruloplasmin;Child;Child, Preschool;Copper/ur [Urine];Developing Countries;Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Penicillamine;Retrospective Studies;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Karim, M. B.;Rahman, M. M.;Islam, M. S.",2007,Jan,,0,0,
377,Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease,"OBJECTIVES: To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. CASE SUMMARY: A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. DISCUSSION: Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20-30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. CONCLUSION: In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned.",Adult;*Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];Fatal Outcome;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Cirrhosis/et [Etiology];Malaysia;Orphan Drug Production;*Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Recurrence;Trace Elements/sd [Supply & Distribution];Trientine/sd [Supply & Distribution];Zinc/sd [Supply & Distribution];0 (Chelating Agents);0 (Trace Elements);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Ping, C. C.;Hassan, Y.;Aziz, N. A.;Ghazali, R.;Awaisu, A.",2007,Feb,https://dx.doi.org/10.1111/j.1365-2710.2007.00794.x,0,0,
378,Wilson's disease,"Progressive hepatolenticular degeneration, or Wilson's disease, is a genetic disorder of copper metabolism. Knowledge of the clinical presentations and treatment of the disease are important both to the generalist and to specialists in gastroenterology and hepatology, neurology, psychiatry, and paediatrics. Wilson's disease invariably results in severe disability and death if untreated. The diagnosis is easily overlooked but if discovered early, effective treatments are available that will prevent or reverse many manifestations of this disorder. Studies have identified the role of copper in disease pathogenesis and clinical, biochemical, and genetic markers that can be useful in diagnosis. There are several chelating agents and zinc salts for medical therapy. Liver transplantation corrects the underlying pathophysiology and can be lifesaving. The discovery of the Wilson's disease gene has opened up a new molecular diagnostic approach, and could form the basis of future gene therapy. [References: 118]",Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];Copper/ur [Urine];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration;Humans;Liver Transplantation;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Ala, A.;Walker, A. P.;Ashkan, K.;Dooley, J. S.;Schilsky, M. L.",2007,Feb 03,https://dx.doi.org/10.1016/S0140-6736(07)60196-2,0,0,
379,Potential protective effects of zinc in iron overload,,Animals;Antioxidants/pd [Pharmacology];Biological Transport;Carrier Proteins;Cation Transport Proteins;Cell Death;Cell Line;Gene Expression Regulation;Hepatolenticular Degeneration;Humans;*Iron Overload/dt [Drug Therapy];Rats;Up-Regulation;*Zinc/pd [Pharmacology];0 (Antioxidants);0 (Carrier Proteins);0 (Cation Transport Proteins);J41CSQ7QDS (Zinc),"Delima, R.;Trinder, D.;Olynyk, J. K.",2007,Feb,https://dx.doi.org/10.1111/j.1478-3231.2006.01428.x,0,0,
380,Patient with late-onset Wilson's disease: deterioration with penicillamine,,Age Factors;Aged;Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];Disease Progression;Fatal Outcome;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Severity of Illness Index;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Sohtaoglu, M.;Ergin, H.;Ozekmekci, S.;Gokdemir, S.;Sonsuz, A.;Arici, C.",2007,Jan 15,https://dx.doi.org/10.1002/mds.21201,0,0,
381,Reply to T.U. Hoogenraad's paper published last April. Zinc therapy in Wilson's disease,,Child;*Copper/ai [Antagonists & Inhibitors];Copper/ur [Urine];Cornea/pa [Pathology];Cornea/pp [Physiopathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Metabolic Clearance Rate/de [Drug Effects];Metabolic Clearance Rate/ph [Physiology];Recovery of Function/de [Drug Effects];Recovery of Function/ph [Physiology];Treatment Outcome;Tremor/dt [Drug Therapy];Tremor/et [Etiology];Tremor/pp [Physiopathology];*Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper),"Marcellini, M.;Sartorelli, M. R.;Nobili, V.",2007,Jan,https://dx.doi.org/10.1016/j.braindev.2006.06.006,0,0,
382,"Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study","BACKGROUND: Wilson's disease is a rare inborn disease related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. Clinical data on larger cohorts are limited owing to low disease frequency. OBJECTIVE AND METHODS: We performed a retrospective analysis of 163 patients with Wilson's disease, examined at the University of Heidelberg, Heidelberg, Germany, to determine clinical presentation, diagnostic course and long-term outcome. RESULTS: Diagnostic criteria for non-caeruloplasmin-bound serum copper, serum caeruloplasmin, 24-h urinary copper excretion, liver copper content, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were reached in 86.6%, 88.2%, 87.1%, 92.7%, 66.3% and 73% of patients, respectively. By analysis of the coding region of ATP7B (except exons 2, 3 and 21), disease-causing mutations were detected in 57% and 29% of patients with Wilson's disease on both chromosomes and on one chromosome, respectively. No mutations were detected in 15% of patients with Wilson's disease. No significant differences were found in clinical parameters or initial presentation between patients grouped according to their mutations. The patients with neurological symptoms were significantly older at the onset of symptoms than patients with hepatitic symptoms (20.2 v 15.5 years of age, p<0.05), and the neurological symptoms were associated with a significantly longer time from onset to diagnosis than hepatic symptoms (44.4 v 14.4 months, p<0.05). After initiating treatment, 76.1% of the patients had a stable or improved course of the disease. Disease progression under treatment was more likely for neuropsychiatric than for hepatic symptoms. Side effects of treatment occurred in 74.4% of patients. CONCLUSIONS: Patients with Wilson's disease having predominantly neuropsychiatric symptoms manifest symptoms later, have a longer time delay from onset of symptoms until definitive diagnosis and have a poorer outcome than patients with hepatic symptoms.","Adenosine Triphosphatases/ge [Genetics];Adolescent;Adult;Cation Transport Proteins/ge [Genetics];Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Cohort Studies;Copper/bl [Blood];Copper/ur [Urine];DNA Mutational Analysis/mt [Methods];Female;Genotype;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Infant;Liver/me [Metabolism];Liver/pa [Pathology];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Phenotype;Retrospective Studies;Trace Elements/tu [Therapeutic Use];Treatment Outcome;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Cation Transport Proteins);0 (Chelating Agents);0 (Trace Elements);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Merle, U.;Schaefer, M.;Ferenci, P.;Stremmel, W.",2007,Jan,https://dx.doi.org/10.1136/gut.2005.087262,1,1,
383,Optimizing therapy of seizures in patients with renal or hepatic dysfunction,"Patients with epilepsy may suffer from renal or hepatic diseases that interfere with their antiepileptic drug (AED) treatment. Furthermore, such diseases may themselves cause seizures. Reduced renal function and hypoalbuminemia lead to accumulation of renally excreted AEDs, such as gabapentin, vigabatrin, topiramate, levetiracetam, and phenytoin. Valproate, lamotrigine, and benzodiazepines are less affected. Low protein-bound AEDs are extensively removed by hemodialysis and supplemental doses are required for dialysis patients. Uremia and related conditions, including intracranial hemorrhage, glucose and electrolyte imbalances, and concomitant drug use, can cause seizures, as can dialysis encephalopathy, primary cerebral lymphoma, fungal infections, and immunosuppressant toxicity in renal transplant recipients. Hepatic dysfunction reduces enzymatic metabolism of AEDs and causes hypoalbuminemia. Gabapentin, topiramate, and levetiracetam are preferred in these conditions, whereas conversely valproate and felbamate are potentially hepatotoxic and should be avoided. Seizures related to hepatic encephalopathy are controlled by oral lactulose or neomycin. Porphyria sufferers may benefit from gabapentin, oxcarbazepine, or levetiracetam. Seizures in Wilson's disease may derive from d-penicillamine-induced pyridoxine deficiency. Effective treatment of seizures in renal and hepatic diseases requires attention to changes in AED pharmacokinetics and adequate care of the underlying illnesses. Monitoring of free drug concentrations is a valuable aid to therapy. [References: 41]",Anticonvulsants/me [Metabolism];Anticonvulsants/pk [Pharmacokinetics];*Anticonvulsants/tu [Therapeutic Use];*Epilepsy/co [Complications];*Epilepsy/dt [Drug Therapy];Epilepsy/et [Etiology];Epilepsy/me [Metabolism];Humans;*Kidney Diseases/co [Complications];Kidney Diseases/me [Metabolism];Kidney Diseases/th [Therapy];*Liver Diseases/co [Complications];Liver Diseases/me [Metabolism];Renal Dialysis;0 (Anticonvulsants),"Lacerda, G.;Krummel, T.;Sabourdy, C.;Ryvlin, P.;Hirsch, E.",2006,Dec 26,,0,0,
384,Membranoproliferative glomerulonephritis in a patient with Wilson's disease,"Wilson's disease is an autosomal recessive disorder of hepatobiliary copper metabolism. Glomerular diseases can ensue during the course of Wilson's disease and membranous nephropathy is the eventual pathology in the majority of these cases. Membranoproliferative glomerulonephritis (MPGN) has rarely been reported in patients with Wilson's disease. Further, in this report, we present a patient with Wilson's disease who had developed MPGN during follow-up due to D-penicillamine therapy. This case is presented to draw attention to the rare association of Wilson's disease and MPGN and to discuss the possible underlying causes.","Adolescent;Chelating Agents/ad [Administration & Dosage];*Chelating Agents/ae [Adverse Effects];*Glomerulonephritis, Membranoproliferative/ci [Chemically Induced];Glomerulonephritis, Membranoproliferative/pa [Pathology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Ozcakar, Z. B.;Ekim, M.;Ensari, A.;Kuloglu, Z.;Yuksel, S.;Acar, B.;Kirsaclioglu, C.;Kansu, A.;Yalcinkaya, F.;Girgin, N.",2006,Nov-Dec,,0,0,
385,Diagnosis and management of Wilson's disease: results of a single center experience,"AIMS: To report on the diagnostic features, management, and clinical outcome after different treatments of Wilson's disease patients followed over a mean period of 15 years. PATIENTS: Thirty-five patients with Wilson's disease referred to the University of Padova's Department of Gastroenterology for diagnosis or treatment were observed for a mean 15 years. The diagnosis was based on clinical symptoms, laboratory tests (ceruloplasmin, urinary, and hepatic copper concentrations), and uptake of the radiostable isotope Cu into the plasma protein pool. Hepatic Cu content was measured by regular follow-up biopsies. Neurologic outcome after therapy was assessed using a newly developed scoring system. RESULTS: Twenty-three (65.7%) patients presented with liver disease; 12 (34.3%) had mixed neurologic and hepatic involvement. All patients had been initially treated with either penicillamine (23) or zinc sulfate (12). The neurologic symptoms became worse or remained stationary in 75% of those treated with penicillamine, whereas zinc treatment improved these symptoms in 90% of treated cases. Both treatments were effective in improving the hepatic symptoms. No differences in hepatic Cu content emerged between follow-up biopsies in either treatment group. Six patients (26%) had to abandon the penicillamine treatment due to side effects. In all, 4 patients underwent liver transplantation, which was successful in 3, with a mean survival after transplantation of 4.6 years; the fourth, who had a severe neurologic impairment, died of central pontine myelinolysis. CONCLUSIONS: Penicillamine and zinc can effectively treat Wilson's disease, though the side effects of penicillamine may be severe enough to prompt its suspension. Liver transplantation remains the treatment of choice for end-stage liver disease.","Adolescent;Adult;Alanine Transaminase/bl [Blood];Alanine Transaminase/de [Drug Effects];Biomarkers/bl [Blood];Biomarkers/ur [Urine];Ceruloplasmin/de [Drug Effects];Ceruloplasmin/me [Metabolism];Chelating Agents/ad [Administration & Dosage];Chelating Agents/ae [Adverse Effects];Child;Child, Preschool;Copper/ur [Urine];Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/th [Therapy];Humans;Isotopes/ur [Urine];Italy/ep [Epidemiology];Liver Transplantation;Magnetic Resonance Imaging;Male;Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];Postoperative Complications/et [Etiology];Postoperative Complications/mo [Mortality];Severity of Illness Index;Survival Analysis;Tomography, X-Ray Computed;Trace Elements/tu [Therapeutic Use];Treatment Outcome;Zinc/tu [Therapeutic Use];0 (Biomarkers);0 (Chelating Agents);0 (Isotopes);0 (Trace Elements);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Medici, V.;Trevisan, C. P.;D'Inca, R.;Barollo, M.;Zancan, L.;Fagiuoli, S.;Martines, D.;Irato, P.;Sturniolo, G. C.",2006,Nov-Dec,https://dx.doi.org/10.1097/01.mcg.0000225670.91722.59,1,1,
386,Psychological presentations without hepatic involvement in Wilson disease,"Wilson disease is an autosomal recessive inborn error of copper metabolism that leads to neurologic symptoms and variable degrees of hepatic damage. The most common characteristic signs clinically are liver disease, psychiatric disease, neurologic disease, or a combination of these. Early recognition by means of clinical signs and an early initiation of therapy using chelators or zinc-salts are essential for a good outcome and prognosis. This report describes a male suffering from Wilson disease who exhibited an unusual presentation that included psychological manifestations without hepatic involvement. He was initially treated for attention-deficit hyperactivity disorder and a seizure disorder until brain imaging established the diagnosis of Wilson disease.","Attention Deficit Disorder with Hyperactivity/di [Diagnosis];Attention Deficit Disorder with Hyperactivity/dt [Drug Therapy];*Attention Deficit Disorder with Hyperactivity/px [Psychology];Brain/pa [Pathology];Cerebral Cortex/pa [Pathology];Child;Copper/ur [Urine];Diagnosis, Differential;Dominance, Cerebral/ph [Physiology];Drug Therapy, Combination;Epilepsies, Partial/di [Diagnosis];Epilepsies, Partial/dt [Drug Therapy];*Epilepsies, Partial/px [Psychology];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/px [Psychology];Humans;Liver Diseases/di [Diagnosis];Liver Diseases/dt [Drug Therapy];*Liver Diseases/px [Psychology];Liver Function Tests;*Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];Rage/de [Drug Effects];*Rage/ph [Physiology];Vitamin B 6/tu [Therapeutic Use];Zinc Compounds/tu [Therapeutic Use];0 (Zinc Compounds);789U1901C5 (Copper);8059-24-3 (Vitamin B 6);GNN1DV99GX (Penicillamine)","Lin, J. J.;Lin, K. L.;Wang, H. S.;Wong, M. C.",2006,Oct,https://dx.doi.org/10.1016/j.pediatrneurol.2006.04.004,0,0,
387,Adverse reaction after tetrathiomolybdate treatment for Wilson's disease: a case report,,"Adult;Copper/ur [Urine];Dose-Response Relationship, Drug;*Enzyme Inhibitors/ae [Adverse Effects];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Male;*Molybdenum/ae [Adverse Effects];Zinc/ur [Urine];0 (Enzyme Inhibitors);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc)","Medici, V.;Trevisan, C. P.;Bigotto, M. A.;D'Inca, R.;Martines, D.;Dal Pont, E.;Sturniolo, G. C.",2006,Nov,https://dx.doi.org/10.1002/mds.21109,0,0,
388,Subcortical white matter abnormalities related to drug resistance in Wilson disease,"Wilson disease (WD) produces typical lesions in the brain, which can aid in diagnosis and therapy. The authors present a drug-resistant WD case with atypical cerebral lesions with marked involvement of white matter as visualized on MRI scans. The diagnosis was confirmed by identification of mutations in the ATP7B gene. The case demonstrates an uncommon pathology-related cerebral copper accumulation and emphasizes the importance of genetic screening in the diagnosis of WD.","Adenosine Triphosphatases/ge [Genetics];Antidotes/tu [Therapeutic Use];*Brain/ab [Abnormalities];*Brain/pa [Pathology];Cation Transport Proteins/ge [Genetics];Child;Cysteine/ge [Genetics];Disease Progression;*Drug Resistance;Follow-Up Studies;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging/mt [Methods];Male;Penicillamine/tu [Therapeutic Use];0 (Antidotes);0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (ATP7A protein, human);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine)","Aikath, D.;Gupta, A.;Chattopadhyay, I.;Hashmi, M. A.;Gangopadhyay, P. K.;Das, S. K.;Ray, K.",2006,Sep 12,https://dx.doi.org/10.1212/01.wnl.0000234130.27871.03,0,0,
389,Regression of nodular liver lesions in Wilson's disease,"Long-term follow-up abdominal imaging studies have not been reported previously in patients with the hepatic form of Wilson's disease (WD). This paper reports the case of a 35-year-old woman with symptoms dating back several months and with multiple, nodular liver lesions. The lesions were hyperdense on non-enhanced computed tomography and hypointense on T2-weighted magnetic resonance (MR) images. A diagnosis of WD was established several weeks after her admission to hospital, and chelating treatment was commenced promptly. No abnormalities were found on follow-up MR examinations of the abdomen and brain 4.5 years later. These imaging features suggest that so long as WD is diagnosed in the initial stages, liver nodules can regress with time and complete healing can be achieved with continuous decoppering treatment.","Adult;Chelating Agents/tu [Therapeutic Use];Diagnosis, Differential;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver/pa [Pathology];Liver Function Tests;Magnetic Resonance Imaging;Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;Ultrasonography/mt [Methods];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Kozic, D.;Svetel, M.;Petrovic, I.;Sener, R. N.;Kostic, V. S.",2006,Sep,https://dx.doi.org/10.1080/02841850600702176,0,0,
390,Wilson's disease: an update,"Wilson's disease (WD) is an inborn error of copper metabolism caused by a mutation to the copper-transporting gene ATP7B. The disease has an autosomal recessive mode of inheritance, and is characterized by excessive copper deposition, predominantly in the liver and brain. Diagnosis of the condition depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring, and a new diagnostic scoring system has recently been proposed. Mutations in ATP7B can occur anywhere along the entire 21 exons, which makes the identification of gene defects particularly challenging. Identification of carriers and presymptomatic family members of affected individuals is achieved by polymerase-chain-reaction-based marker analysis. The traditional treatment for WD is based on copper chelation with agents such as D-penicillamine, but use of this drug has been questioned because of reported side effects. The use of agents such as trientine and ammonium tetrathiomolybdate has been advocated, although results of long-term trials are awaited. In selected cases, orthotropic hepatic transplantation can reverse the basic metabolic abnormality in WD and improve both hepatic and neurological symptoms. Studies of the underlying defects in ATP7B and its suspected modifiers ATOX1 and COMMD1 are expected to unravel the disease's genotype-phenotype correlation, and should lead to the design of improved drugs for ameliorating the suffering of patients. [References: 63]",Adenosine Triphosphatases/ge [Genetics];Brain/pa [Pathology];Cation Transport Proteins/ge [Genetics];Ceruloplasmin/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/et [Etiology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein),"Das, S. K.;Ray, K.",2006,Sep,https://dx.doi.org/10.1038/ncpneuro0291,0,0,
391,Resolution of decompensated cirrhosis from Wilson's disease with zinc monotherapy: a potential therapeutic option?,"BACKGROUND & AIMS: Wilson's disease is a genetic autosomal-recessive copper deposition disorder often presenting with neurologic or hepatic symptoms. In cases of hepatic presentation, treatment usually is initiated with potentially toxic copper chelators, such as D-penicillamine or trientine. Although multiple studies have introduced zinc as a low-toxicity and low-cost Wilson's disease treatment, its use has been limited to adjunctive or single-agent maintenance options. In this report, we describe the use of zinc monotherapy in a patient with severe hepatic presentation of Wilson's disease. METHODS: Zinc has not been evaluated as a single-agent treatment option for active hepatic Wilson's disease. Zinc monotherapy was initiated for a single patient with fulminant hepatic failure caused by Wilson's disease while awaiting liver transplantation. RESULTS: Over a 1-year period with zinc monotherapy, this patient experienced normalization of hepatic synthetic function and resolution of hypoalbuminemia and coagulopathy. Clinical stabilization of variceal bleeds, ascites, and lower-extremity edema also were observed. The patient is no longer a transplant candidate as a result of clinical recovery and improvement of Model for End-stage Liver Disease and Child-Turcotte-Pugh scores. CONCLUSIONS: This case highlights the potential use of zinc as a low-toxicity and low-cost single-agent treatment in severely decompensated hepatic Wilson's disease. Despite promising results in this case, further clinical evaluation will be necessary to assess fully the clinical efficacy of zinc monotherapy.","Female;*Hepatolenticular Degeneration/co [Complications];Humans;*Liver Failure, Acute/dt [Drug Therapy];Liver Failure, Acute/et [Etiology];Middle Aged;Recovery of Function;*Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate)","Lee, V. D.;Northup, P. G.;Berg, C. L.",2006,Aug,https://dx.doi.org/10.1016/j.cgh.2006.04.007,0,0,
392,MR imaging of the brain in Wilson disease of childhood: findings before and after treatment with clinical correlation,"BACKGROUND AND PURPOSE: Although brain MR imaging findings in adult Wilson disease have been described in considerable detail, a paucity of information currently exists regarding brain MR imaging findings in pediatric Wilson disease. The purpose of this study was to analyze the brain MR imaging findings in Wilson disease of childhood at the initial stage and during follow-up after treatment and to correlate these observations with clinical response. METHODS: We evaluated 50 patients with pediatric Wilson disease. Fifty initial and 20 follow-up MR images from 15 patients following penicillamine treatment were analyzed retrospectively, and the data were correlated with clinical findings. RESULTS: Patients were categorized into 3 groups on the basis of initial MR imaging findings. Group I (n = 23) showed normal MR imaging findings. Group II (n = 15) was characterized by T1-weighted images with increased signal intensity in the globus pallidus (n = 15, 100%) followed by the putamen, midbrain, and caudate nucleus. Group III (n = 12) demonstrated T2-weighted images with increased signal intensity in the putamen (n = 10, 83%), followed by the caudate nucleus, globus pallidus, thalamus, midbrain, and pons. There was a significant difference in mean age, the presence of neurologic symptoms, and Child-Pugh classification among the 3 groups (P < .001). Following copper chelating therapy, the changes on follow-up MR imaging were strongly correlated with clinical response to treatment (P < .001). CONCLUSION: Brain MR imaging in children with Wilson disease can be categorized into distinct groups and demonstrated a significant correlation with clinical findings. Interval changes on follow-up MR imaging were also closely correlated with clinical findings and helpful in assessing the clinical response.","Adolescent;*Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;*Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Kim, T. J.;Kim, I. O.;Kim, W. S.;Cheon, J. E.;Moon, S. G.;Kwon, J. W.;Seo, J. K.;Yeon, K. M.",2006,Jun-Jul,,0,0,
393,"A new hepatocytic isoform of PLZF lacking the BTB domain interacts with ATP7B, the Wilson disease protein, and positively regulates ERK signal transduction","The promyelocytic leukemia zinc finger (PLZF) protein has been described as a transcriptional repressor of the BTB-domain/zinc-finger family, and shown to regulate the expression of Hox genes during embryogenesis and the expression of cyclin A in the cell cycle progression. Here, a 45-kDa isoform of PLZF without a BTB domain was identified via yeast two-hybrid screening using the C-terminal region of ATP7B as bait in our determination of the biological roles of the Wilson disease protein outside of its copper-binding domain. Our immunoprecipitation experiments showed that the hepatocytic isoform of PLZF could specifically interact with the C-terminal region of ATP7B. The immunostaining of HepG2 cells revealed that the ATP7B and PLZF proteins were apparently colocalized into the trans-Golgi complexes. It was also determined that disruption of PLZF expression in the HepG2 cells affected an attenuation of ERK activity in a dose-dependent manner. The hepatocytic activities of ERK kinase were found to be enhanced as the result of PLZF or ATP7B expression, but this enhancement was abrogated by the deletion of the C-terminal region of ATP7B. Furthermore, a transgenic Drosophila strain that ectopically expressed the hepatocytic deltaBTB-PLZF exhibited phenotypic changes in eye and wing development, and these alterations were fully recovered as the result of ATP7B expression, indicating the obvious in vivo interaction between the two proteins. Those PLZF-induced abnormalities were attributed to the enhancement of ERK signaling, as was shown by phenotypic reversions with loss-of-function mutations in ERK signal transduction in Drosophila. These data suggest the existence of a mechanism that regulates ERK signaling via the C-terminus of ATP7B and the ATP7B-interacting hepatocytic PLZF. Copyright 2006 Wiley-Liss, Inc.","Adenosine Triphosphatases/ge [Genetics];*Adenosine Triphosphatases/me [Metabolism];Amino Acid Sequence;Animals;Animals, Genetically Modified;Cation Transport Proteins/ge [Genetics];*Cation Transport Proteins/me [Metabolism];Cell Line;Drosophila melanogaster/ah [Anatomy & Histology];Drosophila melanogaster/ph [Physiology];*Extracellular Signal-Regulated MAP Kinases/me [Metabolism];Hepatocytes/cy [Cytology];*Hepatocytes/me [Metabolism];Humans;Kruppel-Like Transcription Factors/ge [Genetics];*Kruppel-Like Transcription Factors/me [Metabolism];*MAP Kinase Signaling System/ph [Physiology];Molecular Sequence Data;Photoreceptor Cells, Invertebrate/me [Metabolism];Photoreceptor Cells, Invertebrate/ul [Ultrastructure];Protein Isoforms/ge [Genetics];*Protein Isoforms/me [Metabolism];Protein Structure, Tertiary;RNA Interference;Sequence Alignment;Two-Hybrid System Techniques;Zinc Fingers;trans-Golgi Network/me [Metabolism];trans-Golgi Network/ul [Ultrastructure];0 (Cation Transport Proteins);0 (Kruppel-Like Transcription Factors);0 (Protein Isoforms);147855-37-6 (ZBTB16 protein, human);EC 2-7-11-24 (Extracellular Signal-Regulated MAP Kinases);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein)","Ko, J. H.;Son, W.;Bae, G. Y.;Kang, J. H.;Oh, W.;Yoo, O. J.",2006,Oct 15,https://dx.doi.org/10.1002/jcb.20980,0,0,
394,Erythrocyte metabolism and antioxidant status of patients with Wilson disease with hemolytic anemia,"Wilson disease (WD) is an autosomal recessive disorder due to the defect in ATP7B gene characterized by excessive accumulation of copper in the liver with progressive hepatic damage and subsequent redistribution to various extrahepatic tissues including the brain, kidneys, and cornea. Strikingly, the total serum copper concentration is always low in WD, even though the non-ceruloplasmin copper level is still expected to be high. To assess the role of free radical reactions catalyzed by non-ceruloplasmin copper, we investigated erythrocyte metabolism and oxidative stress as a mechanism for hemolysis in eight WD patients during episodes of acute hemolysis and compared them with eight follow-up cases of WD on d-penicillamine therapy and eight healthy, age-matched children. Elevated levels of non-ceruloplasmin copper were found in all the WD patients during an episode of hemolytic anemia. There was marked inhibition in erythrocyte enzymes, namely, hexokinase, total adenosine triphosphatase (ATPase), and glucose-6-phosphate dehydrogenase (G-6-PD) from WD patients compared with patients on penicillamine and healthy children, indicating altered erythrocyte metabolism during a hemolytic crisis. Antioxidant status was also found to be compromised as is evident from decreased glutathione (GSH) levels, decreased antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), increased lipid peroxidation, and deranged plasma antioxidants. Uric acid showed maximum decrease followed by ascorbic acid. These findings suggest that the free radical production by elevated non-ceruloplasmin copper through transition metal catalyzed reactions leads to oxidative injury resulting in altered erythrocyte metabolism and severely compromised antioxidant status of WD patients during hemolytic anemia.","Adolescent;Anemia, Hemolytic/ge [Genetics];*Anemia, Hemolytic/me [Metabolism];*Antioxidants/me [Metabolism];Ceruloplasmin/me [Metabolism];Child;Copper/me [Metabolism];*Erythrocytes/me [Metabolism];Female;Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Plasma/me [Metabolism];0 (Antioxidants);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin)","Attri, S.;Sharma, N.;Jahagirdar, S.;Thapa, B. R.;Prasad, R.",2006,Apr,https://dx.doi.org/10.1203/01.pdr.0000203098.77573.39,0,0,
395,Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype,"Mowat-Wilson syndrome is a recently delineated severe mental retardation, multiple congenital anomalies syndrome caused by dominant nonsense or frameshift mutations, deletions or translocations of the zinc finger homeobox 1B gene (ZFHX1B). We report on a patient with exceptional mild phenotype caused by a novel and unusual splice mutation in the 5'UTR. The aberrant transcript leads to usage of an alternative upstream start codon. The resulting protein differs from the wild-type only in the first 24 amino acids. The aberrant protein therefore contains all known functional domains, but might lack a so far unrecognized putative N-terminal acylation site, which is probably important for neuronal function and facial structures. Copyright 2006 Wiley-Liss, Inc. [References: 12]","*5' Untranslated Regions;*Abnormalities, Multiple/ge [Genetics];Acylation;Amino Acid Sequence;Child, Preschool;*Homeodomain Proteins/ge [Genetics];Humans;Infant;Infant, Newborn;*Intellectual Disability/ge [Genetics];Male;Molecular Sequence Data;*Mutation;Phenotype;RNA Splice Sites/ge [Genetics];*Repressor Proteins/ge [Genetics];Syndrome;0 (5' Untranslated Regions);0 (Homeodomain Proteins);0 (RNA Splice Sites);0 (Repressor Proteins);0 (ZEB2 protein, human)","Zweier, C.;Horn, D.;Kraus, C.;Rauch, A.",2006,Apr 15,https://dx.doi.org/10.1002/ajmg.a.31196,0,0,
396,[Corneal and encephalic abnormalities],,Adult;*Brain/ab [Abnormalities];Chelating Agents/tu [Therapeutic Use];*Cornea/ab [Abnormalities];Enzyme Inhibitors/tu [Therapeutic Use];Forecasting;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration;Humans;Magnetic Resonance Imaging;Male;Molybdenum/tu [Therapeutic Use];0 (Chelating Agents);0 (Enzyme Inhibitors);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Le Berre, J. P.;Coutant, G.;Lecoules, S.;Desrame, J.;Amezyane, T.;Bechade, D.;Algayres, J. P.",2006,Aug,https://dx.doi.org/10.1016/j.revmed.2006.01.014,0,0,
397,Paradigm shift in treatment of Wilson's disease: zinc therapy now treatment of choice,"Zinc therapy has replaced penicillamine as first-line therapy for Wilson's disease. New guidelines reflect the paradigm shift in treatment that has occurred in recent years. In the old paradigm, Wilson's disease was seen as genetic disorder associated with the accumulation of copper in the liver and in other organs once the liver had become overloaded with copper. When left untreated, the disease was regarded as uniformly fatal. The old treatment guidelines advised, 'decoppering' with penicillamine because this chelating agent was considered effective in restoring most patients to health. Before the start of treatment, patients were warned that their symptoms could worsen during the first weeks or months of therapy, so as to prevent them from abandoning penicillamine therapy in dismay. In the new paradigm, Wilson's disease is seen as a hereditary disorder associated with copper intoxication. The essence of symptomatic Wilson's disease is poisoning by free copper in the blood, that is, by copper that is not bound to ceruloplasmin. This form of copper is toxic, whereas accumulated copper and copper that is bound to ceruloplasmin or metallothionein is not. The treatment of symptomatic Wilson's disease is no longer aimed at 'decoppering', the removal of accumulated copper, but at the normalization of the free copper concentration in blood, to reverse the copper poisoning. This can be achieved safely and effectively with zinc therapy. Zinc induces metallothionein, a highly effective detoxification protein that binds copper. Oral zinc therapy leads to storage of metallothionein-bound copper in the mucosa of the gut and to the excretion of copper via the stools. New treatment guidelines advise against the use of chelating agents as initial treatment because they may aggravate copper intoxication and cause iatrogenic deterioration.","Administration, Oral;Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Metallothionein/bi [Biosynthesis];Metallothionein/ch [Chemistry];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc)","Hoogenraad, T. U.",2006,Apr,https://dx.doi.org/10.1016/j.braindev.2005.08.008,0,0,
398,Novel therapeutic approaches to the treatment of Wilson's disease,"The treatment of Wilson's disease has changed considerably in recent times, from the use of penicillamine (Cuprimine, Merck) for all stages and types of disease, to the use of three other anticopper drugs at appropriate times for appropriate patients. Each type and stage of the disease can be considered as a therapeutic target, for which specialised therapy is appropriate. This paper systematically reviews the various types and stages of Wilson's disease presentation, and provides opinion on the appropriate therapy for each. For patients presenting with neurological disease, the use of tetrathiomolybdate is optimum; for patients presenting with mild-to-moderate hepatic failure, a combination of trientine (Syprine, Merck) and zinc is recommended, whereas liver transplantation is necessary for those with severe failure; zinc therapy alone or trientine alone as second choice is recommended for patients presenting with hepatitis or cirrhosis without liver failure, for maintenance therapy, for treatment of presymptomatic patients and for treatment of paediatric and pregnant patients. [References: 47]","*Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Clinical Trials as Topic;*Copper;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Molybdenum/tu [Therapeutic Use];*Penicillamine/tu [Therapeutic Use];Pregnancy;Pregnancy Complications/di [Diagnosis];*Pregnancy Complications/dt [Drug Therapy];*Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Brewer, G. J.",2006,Feb,https://dx.doi.org/10.1517/14656566.7.3.317,0,0,
399,Early diagnosis of Wilson Disease in a six-year-old child,,"*Adenosine Triphosphatases/ge [Genetics];*Cation Transport Proteins/ge [Genetics];Child, Preschool;Early Diagnosis;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Liver/de [Drug Effects];Liver/pa [Pathology];Male;*Mutation;Penicillamine/tu [Therapeutic Use];Treatment Outcome;0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Lo Curto, A. G.;Marchi, A.;Grasso, M.;Arbustini, E.;Loudianos, G.;Brega, A.",2006,Jan,https://dx.doi.org/10.1016/j.jpeds.2005.07.040,0,0,
400,Direct diagnosis of Wilson disease by molecular genetics,"In 3 children with chronic liver disease, although multiple studies of copper metabolism were normal, which made the diagnosis of Wilson disease unlikely, analysis of ATP7B gene showed disease causing mutations in all. Molecular diagnosis should be considered in children with enigmatic liver disease, especially those with features of nonalcoholic fatty liver disease.","*Adenosine Triphosphatases/ge [Genetics];Adolescent;Antidotes/tu [Therapeutic Use];*Cation Transport Proteins/ge [Genetics];Child;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Male;*Mutation;Mutation, Missense;Penicillamine/tu [Therapeutic Use];Retrospective Studies;Sequence Deletion;Treatment Outcome;0 (Antidotes);0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine)","Caprai, S.;Loudianos, G.;Massei, F.;Gori, L.;Lovicu, M.;Maggiore, G.",2006,Jan,https://dx.doi.org/10.1016/j.jpeds.2005.07.036,0,0,
401,Penicillamine induced pseudoxanthoma elasticum with elastosis perforans serpiginosa,"Long term D-penicillamine therapy, especially when used to treat Wilson's disease has been shown to cause elastosis perforans serpiginosa, pseudoxanthoma elasticum perforans and other degenerative dermatoses. We report a 23-year-old male patient who presented with multiple firm papules, nodules over the neck, axillae, front of elbows for five years. He was a known case of Wilson's disease on long-term treatment with penicillamine for the past 12 years. The papulonodular lesions were non-tender and some were discrete while others were arranged in a circinate pattern. There was central scarring of the skin within the circinate lesions. In addition, there were several small yellowish papules on both sides of the neck which eventually became confluent to form plaques. Histopathology confirmed the diagnosis of elastosis perforans serpiginosa and pseudoxanthoma elasticum. He was treated with cryotherapy (using liquid nitrogen through cryojet) for former lesions. The lesions showed remarkable improvement after five sittings. Now the patient is under trientine hydrochloride (750 mg twice daily) for Wilson's disease.","Adult;Biopsy, Needle;Cryotherapy/mt [Methods];Dose-Response Relationship, Drug;*Elastic Tissue/pa [Pathology];Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Immunohistochemistry;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Pseudoxanthoma Elasticum/ci [Chemically Induced];*Pseudoxanthoma Elasticum/pa [Pathology];Pseudoxanthoma Elasticum/th [Therapy];Severity of Illness Index;Treatment Outcome;GNN1DV99GX (Penicillamine)","Rath, N.;Bhardwaj, A.;Kar, H. K.;Sharma, P. K.;Bharadwaj, M.;Bharija, S. C.",2005,May-Jun,,0,0,
402,Index of suspicion,,"Chelating Agents/tu [Therapeutic Use];Child;Female;*Gastric Outlet Obstruction/di [Diagnosis];Gastric Outlet Obstruction/et [Etiology];Hematuria/et [Etiology];Hepatitis/et [Etiology];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant;Infant, Newborn;Male;Penicillamine/tu [Therapeutic Use];Pyloric Antrum/ab [Abnormalities];*Renal Veins;Venous Thrombosis/co [Complications];*Venous Thrombosis/di [Diagnosis];Venous Thrombosis/th [Therapy];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Shafagh, H.;Soltani, M. A.;Douvoyiannis, M.;Widness, J.;Di Paola, J.;Yadav, N.;Jatzlau, A.;Pohl, J.;Weir, M.",2005,Dec,,0,0,
403,Control of copper status for cancer therapy,"Copper is a trace element which is tightly regulated in mammals and lower animals. Disruptions of copper homeostasis in humans are rare and they cause serious disorders such as Wilson's disease and Menke's disease. Copper plays an important role in promoting physiological and malignant angiogenesis. Formation of new blood vessels by a tumor enables tumor growth, invasion, and metastasis are copper requiring processes. The copper chelator tetrathiomolybdate (TM), which quickly and effectively depletes copper stores, is under investigation as an anti-angiogenic agent. Promising results from in vitro experiments, in pre-clinical animal models, and in a phase I clinical trial have led to several phase II trials of TM in patients with advanced cancers. [References: 61]","Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;Chelating Agents/tu [Therapeutic Use];Clinical Trials, Phase I as Topic;Clinical Trials, Phase II as Topic;*Copper/ai [Antagonists & Inhibitors];Copper/me [Metabolism];Humans;Molybdenum/tu [Therapeutic Use];*Neoplasms/dt [Drug Therapy];Neoplasms/me [Metabolism];Neoplasms/pa [Pathology];0 (Angiogenesis Inhibitors);0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Goodman, V. L.;Brewer, G. J.;Merajver, S. D.",2005,Nov,,0,0,
404,A case study: identifying a new case of Wilson's disease,"PURPOSE: To present a case of Wilson's disease that presented with fatigue, nausea, abdominal pain, and splenomegaly. Patient information, diagnostic tests, etiology, anatomy and physiology, pathophysiology, assessment, signs and symptoms, diagnosis, medical treatment, nursing interventions, patient education, and research findings related to Wilson's disease are discussed. DATA SOURCES: Case study and scientific literature from Internet, journals, and medical textbooks. CONCLUSIONS: Wilson's disease is a hereditary, autosomal-recessive disease affecting copper excretion. As copper accumulates, signs and symptoms appear. Individuals often present with nonspecific findings, making diagnosis difficult. IMPLICATIONS FOR PRACTICE: This article reviews this rare but potentially devastating disease. Early diagnosis is vital to prevent copper accumulation leading to hepatic cirrhosis, basal ganglia degeneration, and irreversible organ damage. [References: 14]","Abdominal Pain/et [Etiology];Adult;Chelating Agents/tu [Therapeutic Use];Diagnosis, Differential;Drug Monitoring;Drug Therapy, Combination;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;Male;Nausea/et [Etiology];Nurse Practitioners/og [Organization & Administration];Nursing Assessment/mt [Methods];Patient Education as Topic;Penicillamine/tu [Therapeutic Use];Physical Examination/mt [Methods];Physical Examination/nu [Nursing];Primary Health Care/mt [Methods];Trientine/tu [Therapeutic Use];Vomiting/et [Etiology];Zinc Acetate/tu [Therapeutic Use];0 (Chelating Agents);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Noble, J. A.",2005,Dec,https://dx.doi.org/10.1111/j.1745-7599.2005.00089.x,0,0,
405,Combination treatment with penicillamine and trientine in a patient with Wilson's disease,,"Adult;*Chelating Agents/ad [Administration & Dosage];Drug Therapy, Combination;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ad [Administration & Dosage];*Trientine/ad [Administration & Dosage];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Kobayashi, S.;Kodama, H.;Inuzuka, R.;Mori, Y.;Yanagawa, Y.",2005,Oct,https://dx.doi.org/10.1111/j.1442-200x.2005.02106.x,0,0,
406,Anticopper therapy against cancer and diseases of inflammation and fibrosis,"Anticopper drugs that have been developed to treat Wilson's disease, a disease of copper toxicity, include tetrathiomolybdate, zinc, penicillamine, and trientine. Lowering copper levels by a modest amount in non-Wilson's patients with tetrathiomolybdate inhibits angiogenesis, fibrosis and inflammation while avoiding clinical copper deficiency. Through this mechanism tetrathiomolybdate has proven effective in numerous animal models of cancer, retinopathy, fibrosis, and inflammation. Penicillamine has efficacy in rheumatoid arthritis and trientine has efficacy in diabetic neuropathy and diabetic heart disease. If clinical studies support the animal work, anticopper therapy holds promise for therapy of cancer, fibrotic disease and inflammatory and autoimmune diseases. [References: 55]","Animals;*Copper/ai [Antagonists & Inhibitors];Fibrosis;Humans;*Inflammation/dt [Drug Therapy];*Molybdenum/tu [Therapeutic Use];*Neoplasms/dt [Drug Therapy];Neovascularization, Pathologic/pc [Prevention & Control];Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Brewer, G. J.",2005,Aug 15,https://dx.doi.org/10.1016/S1359-6446(05)03541-5,0,0,
407,Two male patients with Wilson's disease treated using trientine and iron reduction therapy,,Adult;*Chelating Agents/tu [Therapeutic Use];*Copper;*Ferritins/bl [Blood];Hemoglobins/me [Metabolism];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Phlebotomy;*Trientine/tu [Therapeutic Use];0 (Chelating Agents);0 (Hemoglobins);789U1901C5 (Copper);9007-73-2 (Ferritins);SJ76Y07H5F (Trientine),"Hayashi, H.;Ueno, T.;Yano, M.;Okada, T.;Mabuchi, H.",2005,Oct,https://dx.doi.org/10.1111/j.1440-1746.2005.03966.x,0,0,
408,[Acute liver failure and hemolysis in a 16-year-old woman. First manifestation of Wilson's disease],"HISTORY AND CLINICAL FINDINGS: A 16-year-old previously healthy female patient was admitted with progressive weakness and jaundice. There was no history of journeys to far-away countries. The patient was on oral contraceptives but no other medication, there were no signs of drug abuse. Apart from scleral and skin jaundice all physical findings were normal. INVESTIGATIONS AND DIAGNOSIS: Diagnostic ultrasound showed an enlarged and hyperdense liver. Laboratory tests revealed a markedly increased serum bilirubin, while aminotransferases were only slightly elevated and alkaline phosphatase was unexpectedly low. Prothrombin and antithrombin III levels were low. There was a Coombs-negative hemolytic anemia. Ceruloplasmin was lower than normal. Based on these findings, acute Wilson's disease was suspected. TREATMENT AND COURSE: The patient was immediately transferred to a hepatologic center with transplantation facilities. There, urinary copper excretion and copper concentration in the liver tissue were found to be elevated. Liver histology showed fibrosis but no cirrhosis. Under conservative therapy with trientine liver function recovered, and the patient is well 3 years after the onset of symptoms. CONCLUSION: Acute liver insufficiency should always suggest the possibility of Wilson's disease, particularly when hemolysis is also present.","Acute Disease;Adolescent;Anemia, Hemolytic/di [Diagnosis];*Anemia, Hemolytic/et [Etiology];Biopsy, Needle;Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Copper/ur [Urine];Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/me [Metabolism];Liver/pa [Pathology];Liver Failure, Acute/di [Diagnosis];Liver Failure, Acute/dg [Diagnostic Imaging];Liver Failure, Acute/dt [Drug Therapy];*Liver Failure, Acute/et [Etiology];Liver Failure, Acute/pa [Pathology];Time Factors;Treatment Outcome;Trientine/tu [Therapeutic Use];Ultrasonography;0 (Chelating Agents);789U1901C5 (Copper);SJ76Y07H5F (Trientine)","Christl, S. U.;Flieger, D.;Keller, R.;Stremmel, W.;Fischbach, W.",2005,Sep 15,https://dx.doi.org/10.1007/s00063-005-1063-8,0,0,
409,Variations in aganglionic segment length of the enteric neural plexus in Mowat-Wilson syndrome,"BACKGROUND/PURPOSE: Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS). In this study, we investigated variations in the enteric neural plexus abnormalities in MWS using morphometry-based histopathologic analysis. METHODS: Seven patients with MWS (3 with mutations in exon 8 of ZFHX1B and 4 with deletions) who had undergone modified Duhamel's operations for Hirschsprung disease were examined. Surgically resected rectosigmoid specimens were analyzed morphometrically. RESULTS: The length of the aganglionic segment was longer than 3 cm in all the patients with deletions. In 3 patients with mutations, the aganglionic region was not detected in the surgically resected specimens; however, the parameters of the ganglions and plexus were significantly smaller than those of controls (cloaca and aproctia), indicative of a transitional zone. Variation in the severity of pathological changes among the 3 patients with mutations was also noted. CONCLUSIONS: The variations in myenteric plexus pathologies in MWS appear to be caused by both variations in ZFHX1B abnormalities and epigenetic factors.","Anthropometry;Child, Preschool;*Colon, Sigmoid/ir [Innervation];Colon, Sigmoid/pa [Pathology];Female;*Hirschsprung Disease/pa [Pathology];Homeodomain Proteins/ge [Genetics];Humans;Male;Mutation;*Rectum/ir [Innervation];Rectum/pa [Pathology];Repressor Proteins/ge [Genetics];0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Ishihara, N.;Shimada, A.;Kato, J.;Niimi, N.;Tanaka, S.;Miura, K.;Suzuki, T.;Wakamatsu, N.;Nagaya, M.",2005,Sep,https://dx.doi.org/10.1016/j.jpedsurg.2005.05.040,0,0,
410,Elastosis perforans serpiginosa secondary to D-penicillamine therapy with coexisting cutis laxa,"Elastosis perforans serpiginosa (EPS) is a rare complication of D-penicillamine therapy. EPS has been reported in patients with Wilson disease, cystinuria, and rheumatoid arthritis after many years of high-dose therapy. We report a case of D-penicillamine-induced EPS with coexisting acquired cutis laxa in a patient with cystinuria. Although both EPS and acquired cutis laxa can be associated with D-penicillamine therapy, few cases have been reported with overlapping clinical presentations, and previously only in patients with Wilson disease. We review the characteristic clinical and histologic features of EPS and discuss the potential dermatologic manifestations of D-penicillamine therapy.",*Chelating Agents/ae [Adverse Effects];*Connective Tissue Diseases/ci [Chemically Induced];Connective Tissue Diseases/pa [Pathology];*Cutis Laxa/co [Complications];Female;Humans;Middle Aged;*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Rosen, L. B.;Muellenhoff, M.;Tran, T. T.;Muhart, M.",2005,Jul,,0,0,
411,Kinetic study of zinc sulphate release from lipophilic matrices prepared for the therapy of Wilson's disease,The rate and extent of drug release from the most controlled release wax matrices are influenced by the drug loading/embedding excipient ratio of the systems. In the present study hydrophobic wax - zinc sulphate matrices with different drug loadings were prepared for the therapy of Wilson's disease. The drug release was tested by the paddle method of USP and the dissolution data were analysed. Both the dissolution rate and kinetic profile can be controlled by alteration in the quantity of embedding material. Matrices of 75% zinc sulphate loadings showed steady state diffusion-controlled matrix release with good correlation in vitro. Good absorption of zinc sulphate from the gastrointestinal tract was proven by significant elevation of serum zinc level in patients with Wilson's disease.,"Absorption;Algorithms;Capsules;Chemistry, Pharmaceutical;Excipients;*Hepatolenticular Degeneration/dt [Drug Therapy];Kinetics;Lipids/ch [Chemistry];Models, Chemical;Porosity;Solubility;Waxes;*Zinc Sulfate/ad [Administration & Dosage];Zinc Sulfate/ch [Chemistry];*Zinc Sulfate/tu [Therapeutic Use];0 (Capsules);0 (Excipients);0 (Lipids);0 (Waxes);7733-02-0 (Zinc Sulfate);8012-89-3 (beeswax)","Nagy, J.;Folhoffer, A.;Horvath, A.;Csak, T.;Taba, G.;Szentmihalyi, K.;Szalay, F.;Zelko, R.",2005,Jul,,0,0,
412,Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma,"Penicillamine is an oral agent used to treat intracerebral copper overload in Wilson's disease. Copper is a known regulator of angiogenesis; copper reduction inhibits experimental glioma growth and invasiveness. This study examined the feasibility, safety, and efficacy of creating a copper deficiency in human glioblastoma multiforme. Forty eligible patients with newly diagnosed glioblastoma multiforme began radiation therapy (6000 cGy in 30 fractions) in conjunction with a low-copper diet and escalating doses of penicillamine. Serum copper was measured at baseline and monthly. The primary end point of this study was overall survival compared to historical controls within the NABTT CNS Consortium database. The 25 males and 15 females who were enrolled had a median age of 54 years and a median Karnofsky performance status of 90. Surgical resection was performed in 83% of these patients. Normal serum copper levels at baseline (median, 130 microg/dl; range, 50-227 microg/dl) fell to the target range of <50 microg/dl (median, 42 microg/dl; range, 12-118 microg/dl) after two months. Penicillamine-induced hypocupremia was well tolerated for months. Drug-related myelosuppression, elevated liver function tests, and skin rash rapidly reversed with copper repletion. Median survival was 11.3 months, and progression-free survival was 7.1 months. Achievement of hypocupremia did not significantly increase survival. Although serum copper was effectively reduced by diet and penicillamine, this antiangiogenesis strategy did not improve survival in patients with glioblastoma multiforme.","Brain Neoplasms/mo [Mortality];*Brain Neoplasms/th [Therapy];*Chelating Agents/to [Toxicity];*Copper/bl [Blood];Diet Therapy;Female;Glioblastoma/mo [Mortality];*Glioblastoma/th [Therapy];Humans;Male;Middle Aged;*Neovascularization, Pathologic/dt [Drug Therapy];*Penicillamine/to [Toxicity];Survival Analysis;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Brem, S.;Grossman, S. A.;Carson, K. A.;New, P.;Phuphanich, S.;Alavi, J. B.;Mikkelsen, T.;Fisher, J. D.;New Approaches to Brain Tumor Therapy, C. N. S. Consortium",2005,Jul,https://dx.doi.org/10.1215/S1152851704000869,0,0,
413,Inhibition kinetics of mushroom tyrosinase by copper-chelating ammonium tetrathiomolybdate,"With a strategy of chelating coppers at tyrosinase active site to detect an effective inhibitor, several copper-specific chelators were applied in this study. Ammonium tetrathiomolybdate (ATTM) among them, known as a drug for treating Wilson's disease, turned out to be a significant tyrosinase inhibitor. Treatment with ATTM on mushroom tyrosinase completely inactivated enzyme activity in a dose-dependent manner. Progress-of-substrate reaction kinetics using the two-step kinetic pathway and dilution of the ATTM revealed that ATTM is a tight-binding inhibitor and high dose of ATTM irreversibly inactivated tyrosinase. Progress-of-substrate reaction kinetics and activity restoration with a dilution of the ATTM indicated that the copper-chelating ATTM may bind slowly but reversibly to the active site without competition with substrate, and the enzyme-ATTM complex subsequently undergoes reversible conformational change, leading to complete inactivation of the tyrosinase activity. Thus, inhibition by ATTM on tyrosinase could be categorized as complexing type of inhibition with a slow and reversible binding. Detailed analysis of inhibition kinetics provided IC50 at the steady-state and inhibitor binding constant (K(I)) for ATTM as 1.0+/-0.2 microM and 10.65 microM, respectively. Our results may provide useful information regarding effective inhibitor of tyrosinase as whitening agents in the cosmetic industry.","*Agaricales/en [Enzymology];*Chelating Agents/me [Metabolism];*Copper/me [Metabolism];Dose-Response Relationship, Drug;*Enzyme Inhibitors/pd [Pharmacology];Inhibitory Concentration 50;Kinetics;*Molybdenum/pd [Pharmacology];*Monophenol Monooxygenase/ai [Antagonists & Inhibitors];*Monophenol Monooxygenase/me [Metabolism];Protein Binding;Structure-Activity Relationship;0 (Chelating Agents);0 (Enzyme Inhibitors);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-14-18-1 (Monophenol Monooxygenase)","Park, K. H.;Park, Y. D.;Lee, J. R.;Hahn, H. S.;Lee, S. J.;Bae, C. D.;Yang, J. M.;Kim, D. E.;Hahn, M. J.",2005,Oct 30,https://dx.doi.org/10.1016/j.bbagen.2005.06.010,0,0,
414,Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2,"BACKGROUND/AIMS: Lysyl-oxidases catalyze the oxidation of lysine residues in collagen and elastin thereby promoting their polymerization. We have studied here the expression of four lysyl-oxidases in normal and diseased human liver. METHODS: The expression of the different lysyl-oxidases in paraffin embedded liver sections was studied using in-situ hybridization and immunohistochemistry. The enzymatic activity of lysyl-oxidase like protein-2 (Loxl2 or LOR-1) using a previously described lysyl-oxidase assay. RESULTS: We have found that the four lysyl-oxidases which we examined are not significantly expressed in the normal liver. By contrast, Wilson's disease and primary biliary cirrhosis (PBC) patients express lysyl-oxidase (Lox) and lysyl-oxidase like protein-2 (Loxl2 or LOR-1) in hepatocytes, and the expression is accompanied by collagen deposition around the hepatocytes. Lysyl-oxidases are also expressed in additional fibrotic liver diseases such as hepatitis B and C but in these diseases the expression is confined to the fibrotic lesions and collagen does not accumulate around hepatocytes. We have found that Loxl2 is able to oxidize lysine residues of collagen, and behaves in that respect similarly to Lox. The copper chelator D-penicillamine inhibits Loxl2 induced oxidation of collagen but the Lox inhibitor beta-aminopropionitrile did not inhibit the oxidation using a BAPN concentration at which Lox activity was completely inhibited. Loxl2 also catalyzed the oxidation of cell surface proteins on HepG2 hepatoblastoma cells and inhibited their proliferation. CONCLUSIONS: Upregulation of Lox and Loxl2 in hepatocytes of Wilson's disease and PBC patients may contribute to liver damage by various mechanisms. The upregulation of Lox and Loxl2 in Wilson's disease could perhaps be utilized for diagnostic purposes since their expression is up-regulated in hepatocytes even before the onset of fibrosis.","*Amino Acid Oxidoreductases/ge [Genetics];Animals;COS Cells;Cell Line, Tumor;Cercopithecus aethiops;Cloning, Molecular;Endothelium, Vascular/en [Enzymology];*Hepatocytes/en [Enzymology];Hepatocytes/pa [Pathology];*Hepatolenticular Degeneration/en [Enzymology];Hepatolenticular Degeneration/pa [Pathology];Humans;In Situ Hybridization;Liver Cirrhosis/en [Enzymology];*Protein-Lysine 6-Oxidase/ge [Genetics];Transfection;EC 1-4 (Amino Acid Oxidoreductases);EC 1-4-3 (LOXL2 protein, human);EC 1-4-3-13 (Protein-Lysine 6-Oxidase)","Vadasz, Z.;Kessler, O.;Akiri, G.;Gengrinovitch, S.;Kagan, H. M.;Baruch, Y.;Izhak, O. B.;Neufeld, G.",2005,Sep,https://dx.doi.org/10.1016/j.jhep.2005.02.052,0,0,
415,Prognostic factors in patients presenting with severe neurological forms of Wilson's disease,"BACKGROUND: Wilson's disease (WD), a metabolic disorder, is believed to be potentially reversible, even in its severe form. However, some patients do not respond to treatment. AIM: To analyse prognostic factors in severe WD. DESIGN: Retrospective audit. METHODS: A total of 140 patients were regularly followed from February 2002 to May 2004. Twenty-nine (18 males, 11 females) had severe disease, as defined by Modified Schwab and England Activities of Daily Living score (MSEADL) of < or=50% or Chu stage of 3. We analysed their clinical, laboratory and MRI features with respect to prognosis. RESULTS: For the severe form, mean age at symptom onset was 11.5 +/- 6.4 years, and at diagnosis, 13.3 +/- 7.0 years. Mean Neurological Symptom Score (NSS), Chu stage, and MSEADL were 26.5 +/- 8.2, 2.7 +/- 0.5 and 24.8 +/- 17.4, respectively. Twenty-one patients underwent MRI; 14 had repeat MRI. Following treatment, 14 (group A) had progressive worsening, including death in two, while 15 (group B) had sustained clinical improvement. Baseline demographic, clinical and laboratory features and MRI scores did not significantly differ between the two groups. However, diffuse white-matter abnormalities were more extensive in group A. Full-dose initial penicillamine therapy could have contributed to worsening in four patients. Drug compliance was poor in both groups but resumption of treatment did not benefit patients in group A. Serial MRI showed regression of lesions only among patients with clinical improvement. DISCUSSION: Severe WD remains a therapeutic challenge, with early diagnosis and treatment are essential. Specific MRI observations, a 'start low-go slow' regimen for penicillamine, and compliance may have prognostic significance. In absence of clinical predictors, genetic attributes need to be explored.","Adolescent;Adult;Chelating Agents/ad [Administration & Dosage];Child;Child, Preschool;Female;*Hepatic Encephalopathy/di [Diagnosis];Hepatic Encephalopathy/dt [Drug Therapy];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Male;Patient Compliance;Penicillamine/ad [Administration & Dosage];Prognosis;Retrospective Studies;0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Prashanth, L. K.;Taly, A. B.;Sinha, S.;Ravishankar, S.;Arunodaya, G. R.;Vasudev, M. K.;Swamy, H. S.",2005,Aug,https://dx.doi.org/10.1093/qjmed/hci095,0,0,
416,An iatrogenic dermatosis with ulceration,,Adult;*Chelating Agents/ae [Adverse Effects];*Drug Eruptions/et [Etiology];Drug Eruptions/pa [Pathology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];*Skin Ulcer/ci [Chemically Induced];Skin Ulcer/pa [Pathology];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Choi, H. J.;Lee, D. K.;Chang, S. E.;Lee, M. W.;Choi, J. H.;Moon, K. C.;Koh, J. K.",2005,Jul,https://dx.doi.org/10.1111/j.1365-2230.2005.01828.x,0,0,
417,Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B). Report of three Italian cases with hypospadias and review,"Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1,000 male births. It is a complex disorder associated with genetic and environmental factors and can be part of genetic syndromes. Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation. It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1). To date, 68 deletion/mutation-positive cases have been reported. Genitourinary anomalies are common in MWS. Here we report that hypospadias is common in males with this syndrome. In 39 patients where this information was available, hypospadias was present in 46% of patients (18/39). In the 3 Italian male cases reported here, hypospadias was always present. MWS should be considered by endocrinologists in patients with hypospadias associated with developmental delays/mental retardation, in particular in the presence of a distinct facial phenotype. Copyright 2005 S. Karger AG, Basel","Child, Preschool;*Chromosomes, Human, Pair 2/ge [Genetics];DNA Mutational Analysis;*Homeodomain Proteins/ge [Genetics];Humans;Hypospadias/co [Complications];*Hypospadias/ge [Genetics];Hypospadias/pa [Pathology];Infant;Infant, Newborn;Intellectual Disability/et [Etiology];Intellectual Disability/pa [Pathology];Male;Microcephaly/et [Etiology];Microcephaly/pa [Pathology];Phenotype;*Point Mutation;*Repressor Proteins/ge [Genetics];Syndrome;0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Garavelli, L.;Cerruti-Mainardi, P.;Virdis, R.;Pedori, S.;Pastore, G.;Godi, M.;Provera, S.;Rauch, A.;Zweier, C.;Zollino, M.;Banchini, G.;Longo, N.;Mowat, D.;Neri, G.;Bernasconi, S.",2005,,https://dx.doi.org/10.1159/000085894,0,0,
418,Copper lowering therapy with tetrathiomolybdate as an antiangiogenic strategy in cancer,"Tetrathiomolybdate (TM) is a novel anticopper agent under development for use in Wilson's disease. It acts by forming a stable tripartite complex with serum albumin and copper, rendering the complexed copper unavailable for cellular uptake. TM is a very potent anticopper agent and has an excellent safety profile. It has been shown that normal copper levels are required for optimal angiogenesis. Based on this background, we decided to evaluate TM as an anticancer agent. TM treatment of Her/2neu mice, genetically programmed to develop breast cancer, completely prevented the development of visible mammary cancers, although avascular microscopic clusters of cancer cells were present in the breasts of TM treated animals. Controls developed grossly visible tumors. TM was able to strongly inhibit tumor growth in six other rodent models. In a phase 1/2 clinical trial of advanced and metastatic cancers, freedom from progression averaged 11 months, and some individual results were quite dramatic. Eight phase 2 studies of specific cancers have been launched. TM's hypothesized mechanism of action is inhibition of angiogenic cytokines. Unlike other current approaches to antiangiogenic therapy which target single agents, we hypothesize that TM inhibits multiple angiogenic cytokines. Part of this effect appears to stem from inhibition of nuclear factor kappa B (NF(K)B), which in turn controls transcription of many angiogenic and other cytokines. However, there are probably multiple mechanisms, in that some angiogenic cytokines appear to have separate mechanisms of copper dependence. The inhibition of multiple angiogenic cytokines gives TM the potential to be a more global inhibitor of angiogenesis. [References: 67]",*Angiogenesis Inhibitors/pd [Pharmacology];*Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;*Copper/ai [Antagonists & Inhibitors];Humans;*Molybdenum/pd [Pharmacology];*Molybdenum/tu [Therapeutic Use];*Neoplasms/dt [Drug Therapy];Neoplasms/pa [Pathology];0 (Angiogenesis Inhibitors);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Brewer, G. J.",2005,May,,0,0,
419,Genes and metals: a deadly combination,"Wilson's disease is an autosomal recessive disease of copper metabolism, with an estimated prevalence of 1:30000. The most common presentations of WD are liver disease and neurological disturbance. For many years the diagnosis was based on the results of several clinical and biochemical tests, for which several limitations had been reported. In recent years the developments of new techniques in genetic and molecular biology have provided useful tools in the diagnosis of Wilson's disease. However, the presence of several mutations and the fact that most patients are compound heterozygote means that the problem is not completely resolved. Chelators and zinc salts have been largely used in the treatment of WD patients with a favorable outcome, but the debate continues as to the agents of first choice. Liver transplantation is a cure for patients with decompensated liver disease but its effect on the neurological outcome is still not clear. [References: 17]","Adolescent;Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Combined Modality Therapy;Copper/bl [Blood];Copper/ur [Urine];Female;Graft Survival;*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Failure/et [Etiology];*Liver Failure/su [Surgery];*Liver Transplantation;Magnetic Resonance Imaging;Male;Prognosis;Risk Assessment;Severity of Illness Index;Survival Rate;Treatment Outcome;Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Dhawan, A.;Ferenci, P.;Geubel, A.;Houwen, R.;Lerut, J.;Sokal, E.",2005,Jan-Mar,,0,0,
420,Status Dystonicus: study of five cases,"Status Dystonicus (SD) is characterized by generalized muscle contractions in dystonic patients. We report 5 cases of SD, two of which in patients with dystonic cerebral palsy, one in a patient with primary segmental dystonia, one in a patient with Hallervorden-Spatz syndrome and one in a patient with Wilson's disease (WD). Three patients were admitted to an intensive care unit and treated with propofol and midazolam, and two were submitted to neurosurgical procedures (bilateral pallidotomy and bilateral pallidal deep brain stimulation). Triggering factors were identified in three patients as follows: infection, stress-induced and zinc therapy for WD. On follow-up, two patients presented with significant improvement of dystonia, whereas the other three cases the clinical picture ultimately returned to baseline pre-SD condition.",Adult;Child;Creatine Kinase/bl [Blood];Dystonic Disorders/bl [Blood];*Dystonic Disorders/dt [Drug Therapy];*Dystonic Disorders/su [Surgery];Electric Stimulation Therapy;Humans;Male;Middle Aged;Stereotaxic Techniques;Treatment Outcome;EC 2-7-3-2 (Creatine Kinase),"Teive, H. A.;Munhoz, R. P.;Souza, M. M.;Antoniuk, S. A.;Santos, M. L.;Teixeira, M. J.;Barbosa, E. R.;Carvalho, R. C.;Scaff, M.;Werneck, L. C.",2005,Mar,https://dx.doi.org/S0004-282X2005000100005,0,0,
421,Wilson's disease presenting with an unusual cough,"A 26-year-old man developed an unusual repetitive, nonproductive cough. Extensive pulmonary and otolaryngology investigations failed to disclose a cause. It was only after he developed additional neurological manifestations ultimately leading to the diagnosis of Wilson's disease (WD) that a neurological basis for the cough was suspected. Features of the cough suggest it was a form of respiratory dyskinesia, a previously unreported presentation of WD. Copyright 2005 Movement Disorder Society.",Adult;Chelating Agents/tu [Therapeutic Use];Cough/dt [Drug Therapy];*Cough/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging/mt [Methods];Male;Molybdenum/tu [Therapeutic Use];Putamen/pa [Pathology];0 (Chelating Agents);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Crone, N. E.;Jinnah, H. A.;Reich, S. G.",2005,Jul,https://dx.doi.org/10.1002/mds.20472,0,0,
422,"Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment","Wilson's disease is a rare autosomal recessive disease of copper accumulation and copper toxicity, due to mutations in the ATP7B gene, which leads to a failure of copper excretion in the bile. It presents clinically primarily as liver disease, psychiatric disease, neurological disease, or a combination of these. The neurological disease is a movement disorder, with abnormalities of speech, tremor, incoordination and dystonia being common features. Diagnosis of neurologically presenting patients is usually straightforward, with Kayser-Fleischer rings and a urine copper over 100 microg/day almost invariably present. In the treatment of neurologically presenting patients, penicillamine should always be avoided, because of the high risk of permanent, drug-induced, additional neurological deterioration. A new drug we have developed, tetrathiomolybdate, given for 8-16 weeks, in combination with zinc, is our first choice for treating these patients. In the absence of availability of tetrathiomolybdate, zinc or trientine are the next best choices. [References: 31]",Behavior;Chelating Agents/tu [Therapeutic Use];Enzyme Inhibitors;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ep [Epidemiology];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Molybdenum/tu [Therapeutic Use];*Nervous System Diseases/dt [Drug Therapy];Nervous System Diseases/ep [Epidemiology];Nervous System Diseases/et [Etiology];*Nervous System Diseases/pp [Physiopathology];Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Enzyme Inhibitors);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Brewer, G. J.",2005,,,0,0,
423,Wilson disease in septuagenarian siblings: Raising the bar for diagnosis,"Wilson Disease (WD) usually presents in the first decades of life, although rare patients have a later presentation. We report the clinical features, diagnostic evaluation, and outcome with treatment of two septuagenarian siblings evaluated as part of a research trial for treatment of neurological WD. The index case was a 72-year-old woman who suffered progressive neurological disability, then developed sub-fulminant liver failure. Her sibling was a 70-year-old man with minimal neurological symptoms and a mild depressive disorder. His liver biopsy revealed only steatosis and minimal fibrosis and an elevated hepatic copper content (671 mug/g dry weight liver). Molecular studies demonstrated compound heterozygosity for disease specific ATP7B mutations E1064A and H1069Q in both patients. Both individuals were treated with trientine and Zn followed by Zn maintenance therapy. Over the last 5 years, the clinical course stabilized and improved, although the index case recently died from bronchopneumonia. In conclusion, advanced age and different clinical presentations of these two subjects with identical ATP7B mutations raises the question of the degree of penetrance for these and other ATP7B mutations. Environmental and extragenic factors are pivotal determinants of disease phenotype. We suggest that WD must be considered at all ages in patients with hepatic disease, neurological disease, or psychiatric symptoms.",Adenosine Triphosphatases/ge [Genetics];Aged;Cation Transport Proteins/ge [Genetics];Female;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;Male;Mutation;Siblings;0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein),"Ala, A.;Borjigin, J.;Rochwarger, A.;Schilsky, M.",2005,Mar,https://dx.doi.org/10.1002/hep.20601,0,0,
424,"Wilson disease: new insights into pathogenesis, diagnosis, and future therapy","Wilson disease is caused by disease-specific mutations of the copper transporting ATPase, ATP7B. The diagnosis is established by clinical and biochemical means, though advances in molecular diagnostics will someday permit de novo diagnosis. The patient may present with hepatic, neurologic, or psychiatric symptoms, or a combination of these. Both environmental and extragenic effects contribute to the varied phenotypic presentations of this disease. Patients can be treated effectively with chelating agents or zinc salts, or with liver transplantation. Liver cell transplant and gene therapy offer potential cures for this disorder, but at present only data from preclinical studies on animal models are available. Future advances in immunotolerization and gene therapy will likely enable human trials for treatment of this disorder and other genetic disorders of hepatic metabolism. [References: 30]",*Adenosine Triphosphatases/ge [Genetics];*Cation Transport Proteins/ge [Genetics];Cell Transplantation/mt [Methods];Female;Forecasting;Genetic Predisposition to Disease;*Genetic Therapy/mt [Methods];*Hepatocytes/tr [Transplantation];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation/mt [Methods];Male;*Penicillamine/tu [Therapeutic Use];Prognosis;Risk Assessment;Severity of Illness Index;Survival Analysis;Treatment Outcome;0 (Cation Transport Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-1 (copper-transporting ATPases);GNN1DV99GX (Penicillamine),"Schilsky, M. L.",2005,Feb,,0,0,
425,Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer's and other CNS diseases,"Metal ions accumulate in the brain with aging and in several neurodegenerative diseases. Aside from the copper storage disease, Wilson's disease, recent attention has focused on the accumulation of zinc, copper and iron in the Alzheimer's disease (AD) brain and the accumulation of iron in Parkinson's disease. In particular, the parenchymal deposition of beta-amyloid (Abeta) and its interaction with metal ions has been postulated to play a role in the progression of AD. Thus, the strategy of lowering brain metal ions and targeting the interaction of Abeta peptide and metal ions through the administration of chelators has merit. Our recent finding that nanoparticle delivery systems can cross the blood-brain barrier has led us to investigate whether chelators delivered conjugated to nanoparticles could act to reverse metal ion induced protein precipitation. In the present studies, the Cu (I) chelator D-penicillamine was covalently conjugated to nanoparticles via a disulfide bond or a thioether bond. Nanoparticle-chelator conjugates were stable between pH 6-8 in aqueous suspension if stored at 4 degrees C, and did not aggregate when challenged with salts and serum. Release of D-penicillamine from the nanoparticles was achieved using reducing agents such as dithiothreitol (as a model for glutathione). Nanoparticles treated only under reducing conditions that released the conjugated D-penicillamine were able to effectively resolubilize copper-Abeta (1-42) aggregates. These results indicate that nanoparticles have potential to deliver D-penicillamine to the brain for the prevention of Abeta (1-42) accumulation, as well as to reduce metal ion accumulation in other CNS diseases.",*Alzheimer Disease/dt [Drug Therapy];Alzheimer Disease/me [Metabolism];Central Nervous System Diseases/dt [Drug Therapy];Central Nervous System Diseases/me [Metabolism];*Chelating Agents/ad [Administration & Dosage];Chelating Agents/pk [Pharmacokinetics];*Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];*Copper;Drug Carriers/ad [Administration & Dosage];Drug Carriers/pk [Pharmacokinetics];Drug Stability;*Nanostructures;Particle Size;*Penicillamine/ad [Administration & Dosage];Penicillamine/pk [Pharmacokinetics];0 (Chelating Agents);0 (Drug Carriers);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Cui, Z.;Lockman, P. R.;Atwood, C. S.;Hsu, C. H.;Gupte, A.;Allen, D. D.;Mumper, R. J.",2005,Feb,https://dx.doi.org/10.1016/j.ejpb.2004.07.009,0,0,
426,Elastosis perforans serpiginosa associated with pseudo-pseudoxanthoma elasticum during treatment of Wilson's disease with penicillamine,"BACKGROUND: Elastosis perforans serpiginosa (EPS) is a reactive perforating dermatosis characterized by the elimination of abnormal elastic fibers from the upper dermis through the epidermis. In a few cases, it occurs as a side effect of treatment by D-penicillamine (DPA). The first case of EPS induced by DPA was described in 1972 in a patient treated for Wilson's disease. Subsequently, cutaneous changes resembling pseudoxanthoma elasticum (PXE) were observed in patients treated with DPA and were reported as pseudo-PXE. CASE REPORT: We report herein the clinical, pathological and ultrastructural study of 2 new cases of DPA-induced EPS and pseudo-PXE. These patients had been treated for Wilson's disease since 14 and 16 years, respectively. Characteristic abnormal elastic fibers were found on histopathological examination of both EPS and pseudo-PXE skin and confirmed by an ultrastructural study. There was no ABCC6 mutation. DISCUSSION: Penicillamine is able to induce widespread, cutaneous and systemic, elastic fiber damage. Our patients present typical features of DPA-induced elastosis, presenting as EPS and pseudo-PXE. ABCC6 mutation is associated with PXE and, as expected, it was absent in our cases of pseudo-PXE. This elastopathy has been related to morphologic changes in elastic fibers secondary to prolonged therapy in most cases. DPA may interfere with elastin cross-linking through inhibition of the enzyme lysyl oxidase, or by formation of complexes with the cross-linked precursors, impairing a normal maturation of elastic fibers. However, no fatal complication of DPA-induced elastopathy has been reported so far. An improvement of the cutaneous lesions is expected after the drug discontinuation.","Adult;*Chelating Agents/ae [Adverse Effects];Diagnosis, Differential;Facial Dermatoses/ci [Chemically Induced];*Facial Dermatoses/di [Diagnosis];Facial Dermatoses/pa [Pathology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Neck;*Penicillamine/ae [Adverse Effects];*Pseudoxanthoma Elasticum/dt [Drug Therapy];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Becuwe, C.;Dalle, S.;Ronger-Savle, S.;Skowron, F.;Balme, B.;Kanitakis, J.;Thomas, L.",2005,,https://dx.doi.org/10.1159/000081487,0,0,
427,"Protection from spontaneous hepatocellular damage by N-benzyl-d-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease","The Long-Evans Cinnamon (LEC) rat is a mutant strain that accumulates excessive tissue copper (Cu) and models the clinical symptoms and biological features of Wilson's disease in humans. We compared the effects of three metal chelating agents, N-benzyl-d-glucamine dithiocarbamate (BGD), d-penicillamine (D-PEN), and triethylenetetramine (TETA), on the biliary and urinary excretions of Cu using LEC rats. The animals were treated ip with each chelating agent (1 mmol/kg body weight) and then the bile and urine samples were collected for 3 h. Because single treatment with BGD markedly stimulated biliary excretion of Cu, the protective effect of repeated BGD injection on spontaneous hepatocellular damage was further examined. Separate groups received two weekly injections of BGD starting at 11 weeks of age and were compared to saline-injected controls. Serum alanine aminotransferase (ALT) activity and bilirubin level were significantly increased in control LEC rats by 19 weeks of age and histopathological analysis demonstrated extensive hepatic damage in these rats. However, repeated BGD injections prevented the increases in serum ALT and bilirubin and blocked the histopathological changes in the liver. Furthermore, although Cu rapidly accumulated in the liver, kidney, spleen, and serum of control LEC rats during the test period, repeated BGD injection largely prevented these increases. These results indicate that BGD treatment is effective in blocking excessive Cu accumulation in LEC rats that, in turn, provides protection from spontaneous liver damage.","Animals;Body Weight/de [Drug Effects];*Chelating Agents/pd [Pharmacology];Copper/me [Metabolism];Disease Models, Animal;Dose-Response Relationship, Drug;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;*Liver/de [Drug Effects];Liver/pa [Pathology];Rats;Rats, Long-Evans;*Sorbitol/aa [Analogs & Derivatives];*Sorbitol/pd [Pharmacology];*Thiocarbamates/pd [Pharmacology];0 (Chelating Agents);0 (Thiocarbamates);506T60A25R (Sorbitol);789U1901C5 (Copper);M0OU990U9P (N-benzylglucamine dithiocarbamate)","Shimada, H.;Takahashi, M.;Shimada, A.;Okawara, T.;Yasutake, A.;Imamura, Y.;Kiyozumi, M.",2005,Jan 01,https://dx.doi.org/10.1016/j.taap.2004.06.005,0,0,
428,Recent clinical features of Wilson's disease with hepatic presentation,"BACKGROUND: We carried out this study to evaluate recent clinical features of Wilson's disease (WD) with hepatic presentation, especially in terms of age, degree of liver injury, and association with hepatocellular carcinoma (HCC). METHODS: Sixteen patients with hepatic manifestations were diagnosed with WD in the period 1976-2003. We divided this period into two periods, ""past"" and ""recent"". The diagnosis was based on the presence of Kayser-Fleisher rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge, and increased hepatic copper concentrations. This retrospective study was done at Ehime University Hospital. RESULTS: Four patients, including a pair of siblings, had a family history of WD. Four patients had parental consanguinity. There were 6 patients aged over 40 years in the recent period, whereas no patients in the past period were over 40. Four patients had neurological manifestations. Ten patients had liver cirrhosis and 5 had chronic hepatitis. Two had fatty liver without obesity. All patients in the past period had liver cirrhosis. Three patients with liver cirrhosis were found to have HCC during the follow up. All patients were treated with either D-penicillamine or trientine chloride, or both. However, four patients had to discontinue these agents due to the side effects. CONCLUSIONS: Recently, the number of patients diagnosed with WD has been increasing, not only in terms of those with classical-type WD but also in terms of elderly patients or patients with non-cirrhotic liver injury such as fatty liver and chronic hepatitis. The various clinical features of WD should be recognized and particular attention should focus on HCC as a complication.","Adolescent;Adult;Aged;*Carcinoma, Hepatocellular/co [Complications];Carcinoma, Hepatocellular/ep [Epidemiology];Child;Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Humans;Liver Diseases/ep [Epidemiology];Liver Diseases/et [Etiology];*Liver Neoplasms/co [Complications];Liver Neoplasms/ep [Epidemiology];Male;Middle Aged;Retrospective Studies","Kumagi, T.;Horiike, N.;Michitaka, K.;Hasebe, A.;Kawai, K.;Tokumoto, Y.;Nakanishi, S.;Furukawa, S.;Hiasa, Y.;Matsui, H.;Kurose, K.;Matsuura, B.;Onji, M.",2004,Dec,https://dx.doi.org/10.1007/s00535-004-1466-y,1,1,
429,Value of an enzymatic assay for the determination of serum ceruloplasmin,"The serum concentration of the copper protein ceruloplasmin has been an important diagnostic indicator of Wilson's disease (WD). It is widely quoted that 95% of people with WD have low serum ceruloplasmin concentrations. Current evidence suggests that a normal serum ceruloplasmin concentration is more common in patients with WD, particularly those with liver disease, perhaps in part because of the routine use of an immunologic assay. This assay might indicate a normal level of ceruloplasmin when the enzymatic activity is lower. Enzymatic activity is the biologically relevant parameter. We compared the immunologic measurement with the enzymatic assessment of oxidase activity in patients with liver or neurologic symptoms of unknown origin in whom WD was considered in the differential diagnosis. Although a strong correlation of ceruloplasmin protein concentration with oxidase activity was observed in controls, this was not the case for these patients. Twelve patients, presenting with various types of hepatic disease, demonstrated a weak correlation between ceruloplasmin protein concentration and oxidase activity. Ten percent of patients with neurologic symptoms ( n = 41) had low ceruloplasmin concentrations and oxidase activity, and another 8% had normal ceruloplasmin concentrations associated with low oxidase activity. Although the enzymatic method is preferred for its biologic relevance, ceruloplasmin analysis is not a reliable diagnostic parameter for the diagnosis of WD in patients with liver disease. An important use of the ceruloplasmin oxidase assay is in the follow-up of patients with WD. Ceruloplasmin oxidase activity was undetectable in sera from patients with WD who were undergoing long-term chelation therapy, suggesting an early sign of copper depletion and a need for subsequent monitoring for symptoms of copper deficiency.",*Ceruloplasmin/an [Analysis];*Ceruloplasmin/me [Metabolism];Chelating Agents/ad [Administration & Dosage];Copper/bl [Blood];Edetic Acid;Evaluation Studies as Topic;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Immunoenzyme Techniques/mt [Methods];Male;Penicillamine/ad [Administration & Dosage];Plasma;0 (Chelating Agents);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Macintyre, G.;Gutfreund, K. S.;Martin, W. R.;Camicioli, R.;Cox, D. W.",2004,Dec,https://dx.doi.org/10.1016/j.lab.2004.08.005,0,0,
430,"Wilson disease: pathophysiology, diagnosis, treatment, and screening","Wilson disease is an autosomal recessive condition of copper metabolism that was once considered fatal. The identification of the gene for Wilson disease has led to a better understanding of the molecular defect underlying this disorder and has impacted on disease diagnosis for some individuals. Medical therapy with chelating agents or zinc salts remains the mainstay of therapy for most patients, and liver transplant is lifesaving for those with advanced disease refractory to medical therapy or with fulminant hepatic failure. Future cell-based and genetic therapies may provide a cure for this disorder. [References: 64]",Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];Genetic Therapy;Genotype;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver Transplantation;Phenotype;Zinc Compounds/tu [Therapeutic Use];0 (Chelating Agents);0 (Zinc Compounds);789U1901C5 (Copper),"Ala, A.;Schilsky, M. L.",2004,Nov,https://dx.doi.org/10.1016/j.cld.2004.06.005,0,0,
431,Copper inhibits the water and glycerol permeability of aquaporin-3,"Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several other tissues. Erythrocytes are, together with kidney and liver, the main targets for copper toxicity. Here we report that both water and glycerol permeability of human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the natural buffer system in our body, doses in the range of those observed in Wilson disease and in copper poisoning caused significant inhibition. AQP7, another aquaglyceroporin, was insensitive to copper. Three extracellular amino acid residues, Trp128, Ser152, and His241, were identified as responsible for the effect of copper on AQP3. We have previously shown that Ser152 is involved in regulation of AQP3 by pH. The fact that Ser152 mediates regulation of AQP3 by copper may explain the phenomenon of exquisite sensitivity of human erythrocytes to copper at acidic pH. When AQP3 was co-expressed with another AQP, only glycerol but not water permeability was inhibited by copper. Our results provide a better understanding of processes that occur in severe copper metabolism defects such as Wilson disease and in copper poisoning.","Amino Acids/ch [Chemistry];Aquaporin 3;*Aquaporins/ai [Antagonists & Inhibitors];Aquaporins/ch [Chemistry];Aquaporins/ge [Genetics];*Aquaporins/me [Metabolism];Cell Line;Copper/me [Metabolism];*Copper/to [Toxicity];Glycerol/me [Metabolism];Humans;Lead/to [Toxicity];Models, Molecular;Nickel/to [Toxicity];Permeability/de [Drug Effects];Recombinant Fusion Proteins/ai [Antagonists & Inhibitors];Recombinant Fusion Proteins/ch [Chemistry];Recombinant Fusion Proteins/ge [Genetics];Recombinant Fusion Proteins/me [Metabolism];Transfection;Water/me [Metabolism];Zinc/to [Toxicity];0 (AQP3 protein, human);0 (AQP7 protein, human);0 (Amino Acids);0 (Aquaporins);0 (Recombinant Fusion Proteins);059QF0KO0R (Water);158801-98-0 (Aquaporin 3);2P299V784P (Lead);789U1901C5 (Copper);7OV03QG267 (Nickel);J41CSQ7QDS (Zinc);PDC6A3C0OX (Glycerol)","Zelenina, M.;Tritto, S.;Bondar, A. A.;Zelenin, S.;Aperia, A.",2004,Dec 10,https://dx.doi.org/10.1074/jbc.M407645200,0,0,
432,Effect of D-penicillamine on neuromuscular junction in patients with Wilson disease,,"Adolescent;Adult;Autoantibodies/bl [Blood];Autoantibodies/im [Immunology];Child;Cohort Studies;Enzyme-Linked Immunosorbent Assay;Female;Follow-Up Studies;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/im [Immunology];Humans;Male;Myasthenia Gravis/ci [Chemically Induced];*Myasthenia Gravis/et [Etiology];Myasthenia Gravis/im [Immunology];*Neuromuscular Junction/de [Drug Effects];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Prospective Studies;Receptors, Cholinergic/im [Immunology];Single-Blind Method;0 (Autoantibodies);0 (Receptors, Cholinergic);GNN1DV99GX (Penicillamine)","Komal Kumar, R. N.;Patil, S. A.;Taly, A. B.;Nirmala, M.;Sinha, S.;Arunodaya, G. R.",2004,Sep 14,,0,0,
433,Infant with severe penicillamine embryopathy born to a woman with Wilson disease,"We report a chromosomally normal infant boy with congenital diffuse cutis laxa, severe micrognathia, contractures of all limbs, and central nervous system abnormalities including agenesis of the corpus callosum, born to a woman taking D-penicillamine (DP) for Wilson disease (WD) throughout her pregnancy. His postnatal course was remarkable for chronic lung disease, profound developmental delays, and probable cortical blindness, as well as resolution of his cutis laxa. Embryopathy is a rare complication in babies born to pregnant women treated with DP, and there have been only seven previous reports of birth defects in exposed infants (three of which had favorable postnatal outcomes). The etiology of the severe outcome in this boy is unclear, but prenatal measurement of maternal copper and zinc levels may be indicated for management. Copyright 2004 Wiley-Liss, Inc.","*Abnormalities, Drug-Induced/di [Diagnosis];Agenesis of Corpus Callosum;Cutis Laxa/di [Diagnosis];Female;*Fetal Diseases/ci [Chemically Induced];Fetal Diseases/di [Diagnosis];Fetus/ab [Abnormalities];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant;Limb Deformities, Congenital/di [Diagnosis];Lung Diseases/di [Diagnosis];Male;Micrognathism/di [Diagnosis];Nervous System Malformations/di [Diagnosis];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Pregnancy;Syndrome;GNN1DV99GX (Penicillamine)","Pinter, R.;Hogge, W. A.;McPherson, E.",2004,Jul 30,https://dx.doi.org/10.1002/ajmg.a.10871,0,0,
434,Zinc deficiency: its characterization and treatment,,"Child;Child, Preschool;Common Cold/dt [Drug Therapy];*Deficiency Diseases/dt [Drug Therapy];Deficiency Diseases/et [Etiology];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant;Parenteral Nutrition, Total;*Zinc/df [Deficiency];*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc)","Prasad, A. S.",2004,,,0,0,
435,Metal contents of liver parenchyma after percutaneous ethanol injection or radiofrequency ablation in patients with hepatocellular carcinoma before and after trientine hydrochloride therapy,"We administered trientine hydrochloride, a drug used in the treatment of Wilson's disease, to patients with hepatocellular carcinoma after radical treatment with percutaneous ethanol injection or radiofrequency ablation, and examined its effect on the reduction of liver-tissue copper content. We enrolled 24 patients with 3 or fewer primary lesions of Child class A or B hepatocellular carcinoma with diameters of 3 cm or less who had undergone radical treatment with percutaneous ethanol injection or radiofrequency ablation. Trientine hydrochloride was orally administered in a single daily dose of 250 mg to 12 patients before a meal (at fasting, group 1) or at a total daily dosage of 750 mg, divided into 3 doses, to 12 patients (group 2). This study was a randomized between-groups comparative study of 12 weeks' duration. We used the particle-induced x-ray-emission method to determine liver-tissue mineral content. Urine copper and serum mineral levels were also measured, and transaminase levels were examined. Liver-tissue copper content decreased significantly, to 160.1 microg/g dry weight, after treatment, compared with the pretreatment level of 306.8 microg/g dry weight (P <.05). We detected no significant difference in iron or zinc content before and after treatment. The copper content was significantly reduced after treatment in both groups (P <.05). The urine copper level was significantly increased after 1 week of treatment but decreased thereafter. Serum copper levels were significantly reduced after treatment (P <.01). We detected no significant difference in transaminase level before and after treatment. Iron-deficiency anemia in 1 patient after 12 weeks' treatment was the only adverse reaction, and it was improved by the administration of an iron product. We noted no other overt adverse reactions. In patients with hepatocellular carcinoma, trientine hydrochloride therapy may significantly reduce copper content in liver tissue.","Aged;Carcinoma, Hepatocellular/dt [Drug Therapy];*Carcinoma, Hepatocellular/me [Metabolism];*Carcinoma, Hepatocellular/th [Therapy];Chelating Agents/ad [Administration & Dosage];*Chelating Agents/tu [Therapeutic Use];Combined Modality Therapy;Copper/bl [Blood];*Copper/me [Metabolism];Copper/ur [Urine];Ethanol/ad [Administration & Dosage];Ethanol/tu [Therapeutic Use];Female;Humans;Iron/me [Metabolism];Liver Neoplasms/dt [Drug Therapy];*Liver Neoplasms/me [Metabolism];*Liver Neoplasms/th [Therapy];Male;Middle Aged;Radio Waves/tu [Therapeutic Use];Trientine/ad [Administration & Dosage];*Trientine/tu [Therapeutic Use];Zinc/me [Metabolism];0 (Chelating Agents);3K9958V90M (Ethanol);789U1901C5 (Copper);E1UOL152H7 (Iron);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Fukuda, H.;Ebara, M.;Okabe, S.;Yoshikawa, M.;Sugiura, N.;Saisho, H.;Kondo, F.;Yukawa, M.",2004,Jun,https://dx.doi.org/10.1016/j.lab.2004.02.010,0,0,
436,Copper deficiency as an anti-cancer strategy,"Copper is a tightly regulated trace element. Disruptions of copper homeostasis are rare and they cause serious disorders such as Wilson's disease and Menkes disease. Copper also plays an important role in promoting physiological and malignant angiogenesis. Formation of new blood vessels by a tumor enables tumor growth, invasion and metastasis. The copper chelator tetrathiomolybdate (TM), which quickly and effectively depletes copper stores, is under investigation as an anti-angiogenic agent. Promising results in vitro, in pre-clinical animal models and in an early (phase I) clinical trial have led to ongoing phase II evaluation of TM in patients with advanced cancers. Copyright 2004 Society for Endocrinology [References: 68]","*Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;*Chelating Agents/tu [Therapeutic Use];*Copper/df [Deficiency];Humans;*Molybdenum/tu [Therapeutic Use];*Neoplasms/bs [Blood Supply];Neoplasms/dt [Drug Therapy];*Neovascularization, Pathologic/pc [Prevention & Control];0 (Angiogenesis Inhibitors);0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Goodman, V. L.;Brewer, G. J.;Merajver, S. D.",2004,Jun,,0,0,
437,"In vitro assessment of copper-induced toxicity in the human hepatoma line, Hep G2","Copper, though essential, is highly toxic when present in excess, as in Wilson disease, a genetic disorder of hepatic copper metabolism. We hypothesized that mitochondria are a major target of copper-induced cytotoxicity in Wilson disease. We used the human hepatoma line Hep G2 to examine copper-mediated cytotoxicity and three different methods to assess organelle damage: MTT assay (mitochondria), neutral red (NR; lysosomes) and Trypan blue exclusion assay (TB; plasma membrane). For all assays, cells at approximately 60% confluence in microtitre plates were incubated with CuCl(2) (concentration range: 50-100-150-200 microM) for 24 or 48 h. Results were expressed as percent of untreated control. At 24 h, cytotoxicity as detected by NR assay was significantly higher at all concentrations of copper than for MTT or TB ( p<0.005 at all concentrations). Cytotoxicity as detected by MTT was higher than that detected by TB at all concentrations except at 200 microM (p<0.05 for 50 microM, p<0.005 for 100 microM, p = 0.001 for 150 microM). Results at 48 h were similar (NR versus others: p <0.001 MTT versus TB: NS except at 150 microM where p<0.01). We investigated reactive oxygen species (ROS) production in copper-associated hepatocytoxicity by incubating sub-confluent cells with 2('),7(')-dichlorodihydrofluorescein diacetate dye plus copper (concentration range: 0-200 microM) for 1-1.5 h. Copper, but not zinc, produced significant increases in ROS (p<0.001). In summary, Hep G2 lysosomes appeared more susceptible to Cu-mediated damage than mitochondria; the cell membrane was highly resistant to damage.","Carcinoma, Hepatocellular/pa [Pathology];Coloring Agents;*Copper/to [Toxicity];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver Neoplasms/pa [Pathology];Lysosomes/pa [Pathology];*Mitochondria/pa [Pathology];Neutral Red;Reactive Oxygen Species;Tetrazolium Salts;Thiazoles;Trypan Blue;Tumor Cells, Cultured;0 (Coloring Agents);0 (Reactive Oxygen Species);0 (Tetrazolium Salts);0 (Thiazoles);261QK3SSBH (Neutral Red);789U1901C5 (Copper);EUY85H477I (thiazolyl blue);I2ZWO3LS3M (Trypan Blue)","Seth, R.;Yang, S.;Choi, S.;Sabean, M.;Roberts, E. A.",2004,Aug,https://dx.doi.org/10.1016/j.tiv.2004.01.006,0,0,
438,Zinc sulphate release and morphology of matrices prepared for the individual therapy of Wilson's disease,"Hydrophobic zinc sulphate wax matrices with different drug loadings were prepared for the individual hospital therapy of Wilson's disease. The drug release parameters, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) of the samples were analysed. The release mechanisms from matrices of 75% and 80% w/w zinc sulphate loadings were described with good correlation by the semi-empirical Fikkian diffusion based release model. Besides the zinc sulphate diffusion through the pores of the wax matrices, the parallel diffusion of zinc sulphate from the matrix surface is dominant in the case of samples of 83% and 90%w/w drug loadings. The combination of SEM and EDS analysis visualizes the morphology of the matrices and the related composition thus explaining the differences in the release characteristics.","Algorithms;Delayed-Action Preparations;Excipients;*Hepatolenticular Degeneration/dt [Drug Therapy];Microscopy, Electron, Scanning;Spectrometry, X-Ray Emission;Waxes;*Zinc Sulfate/ad [Administration & Dosage];*Zinc Sulfate/tu [Therapeutic Use];0 (Delayed-Action Preparations);0 (Excipients);0 (Waxes);7733-02-0 (Zinc Sulfate)","Nagy, J.;Vajna, M.;Devenyi, L.;Zelko, R.",2004,Apr,,0,0,
439,Molecular screening of the ZFHX1B gene in prenatally diagnosed isolated agenesis of the corpus callosum,"OBJECTIVE: Agenesis of the corpus callosum (ACC) is the most common malformation of the central nervous system and may be associated with mental retardation. ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. Other manifestations involve Hirschsprung disease, cardiac defects, renal abnormalities and hypospadias. Among this broad spectrum of malformations recently associated with haploinsufficiency of the zinc finger homeobox 1B gene (ZFHX1B), ACC can therefore be the only feature to be detected prenatally. Thus, we studied a group of 18 fetuses terminated for ACC and performed mutational analysis of the ZFHX1B gene in six selected cases. METHODS: Diagnosis of agenesis of the ACC was performed by prenatal echography survey. Screening for ZFHX1B deletions was performed by poly (CA) microsatellite markers studies and real-time semi-quantitative PCR. Mutational analysis was performed by single-strand conformation polymorphisms analysis (SSCP). RESULTS: Neither deletion encompassing the ZFHX1B locus nor mutation could be detected in any of the six fetuses analysed. CONCLUSION: ZFHX1B is not a major gene in isolated ACC. However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS. Copyright 2004 John Wiley & Sons, Ltd.","*Agenesis of Corpus Callosum;Corpus Callosum/dg [Diagnostic Imaging];*DNA Mutational Analysis;Diagnosis, Differential;Female;Gene Deletion;Gestational Age;*Homeodomain Proteins/ge [Genetics];Humans;Male;Microsatellite Repeats;Mutation;Polymerase Chain Reaction;Polymorphism, Single-Stranded Conformational;Pregnancy;*Repressor Proteins/ge [Genetics];*Ultrasonography, Prenatal;0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Espinosa-Parrilla, Y.;Encha-Razavi, F.;Attie-Bitach, T.;Martinovic, J.;Morichon-Delvallez, N.;Munnich, A.;Vekemans, M.;Lyonnet, S.;Amiel, J.",2004,Apr,https://dx.doi.org/10.1002/pd.865,0,0,
440,Plasma D-penicillamine redox state evaluation by capillary electrophoresis with laser-induced fluorescence,"D-Penicillamine (D-Pen) is a thiol drug used in the treatment of Wilson's disease, rheumatoid arthritis, metal intoxication and cystinuria. We have recently described a new capillary electrophoresis (CE) method to measure physiological thiols, in which separation of total plasma homocysteine, cysteine, cysteinylglycine, glutathione is achieved using the organic base N-methyl-D-glucamine in the run buffer. In this paper, we present an improvement of our method that allows a baseline separation of total plasma D-Pen from the physiological thiols. Moreover, reduced, free and protein-bound forms of drug are measured by varying the order of disulfide reduction with tributylphosphine and proteins precipitation with 5-sulphosalicylic acid (SSA). After derivatization with 5-iodoacetamidofluorescein (5-IAF), samples are separated and measured by capillary electrophoresis with laser-induced fluorescence in an uncoated fused-silica capillary (57 x 75 microm i.d.) using a phosphate/borate run buffer pH 11.4. In these conditions, the migration time of D-Pen is about 7 min and the time required for each analysis is roughly 10 min. The proposed method has been utilized to measure the various forms of the drug in a D-Pen administered Wilson's disease patient.",Fluorescence;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lasers;Oxidation-Reduction;*Penicillamine/bl [Blood];Penicillamine/tu [Therapeutic Use];Reproducibility of Results;Sensitivity and Specificity;GNN1DV99GX (Penicillamine),"Zinellu, A.;Carru, C.;Sotgia, S.;Deiana, L.",2004,Apr 25,https://dx.doi.org/10.1016/j.jchromb.2004.01.002,0,0,
441,"Zinc for prostate disease and other conditions: a little evidence, a lot of hype, and a significant potential problem","Dietary and supplemental zinc, especially in excess, has received much attention in numerous alternative medicine resources. There is a small amount of medical evidence that zinc may alleviate some mostly rare medical conditions (such as Wilson's disease). However, in prostate conditions, such as BPH, large concentrations of zinc are found in the prostate gland. Excess intake of zinc, especially with individual supplements, has the potential to encourage the growth of prostate conditions from BPH to cancer. In fact, one large study found a significantly higher risk of advanced prostate cancer in men consuming large intakes of these supplements. Large doses of zinc can inhibit the benefits of bisphosphonate drugs, increase testosterone level, increase cholesterol, reduce levels of ""good cholesterol"" or HDL, and can promote immune dysfunction. More research is needed in this area, but in the meantime, the time seems more than ripe to discourage or immediately discontinue the intake of larger concentrations of zinc for most individuals until adequate research resolves this controversial issue. [References: 33]",Dietary Supplements;Humans;Male;Nutrition Policy;*Prostatic Hyperplasia/dt [Drug Therapy];*Prostatic Neoplasms/dt [Drug Therapy];Zinc/ae [Adverse Effects];*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc),"Moyad, M. A.",2004,Feb,,0,0,
442,Mowat-Wilson syndrome and mutation in the zinc finger homeo box 1B gene: a well defined clinical entity,,"Abnormalities, Multiple/di [Diagnosis];*Abnormalities, Multiple/ge [Genetics];Adolescent;Child, Preschool;Craniofacial Abnormalities/di [Diagnosis];*Craniofacial Abnormalities/ge [Genetics];Female;Hirschsprung Disease/di [Diagnosis];*Hirschsprung Disease/ge [Genetics];*Homeodomain Proteins/ge [Genetics];Humans;Intellectual Disability/di [Diagnosis];*Intellectual Disability/ge [Genetics];Male;Microcephaly/di [Diagnosis];*Microcephaly/ge [Genetics];*Mutation/ge [Genetics];*Repressor Proteins/ge [Genetics];Seizures/di [Diagnosis];*Seizures/ge [Genetics];Syndrome;Zinc Fingers/ge [Genetics];0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Cerruti Mainardi, P.;Pastore, G.;Zweier, C.;Rauch, A.",2004,Feb,,0,0,
443,Atypical childhood Wilson's disease,"Wilson's disease is a genetic disorder of copper metabolism with a hepatic or neurologic presentation. A hepatic presentation is more common in young children. Neurologic Wilson's disease often manifests as a movement disorder with dystonia, tremor, and dysarthria. Psychiatric or behavioral symptoms can also be a presenting feature of Wilson's disease. We describe an atypical neurologic presentation in a prepubertal child with minimal hepatic involvement; in which transient hemiparesis and encephalopathy dominated her initial neurologic presentation. Brain magnetic resonance imaging revealed extensive cortical and subcortical signal change, in addition to the classical basal ganglia signal abnormality observed in Wilson's disease. She was treated with oral tetrathiomolybdate anticopper therapy, followed by zinc maintenance. Her clinical status and brain imaging improved considerably at 1 year after treatment initiation. Neurologic Wilson's disease may have diverse presentations, and should be considered in children who present with cortical features and signal change on magnetic resonance imaging.","Child;Diagnosis, Differential;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Molybdenum/tu [Therapeutic Use];81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","Carlson, M. D.;Al-Mateen, M.;Brewer, G. J.",2004,Jan,,0,0,
444,Review article: diagnosis and current therapy of Wilson's disease,"Wilson's disease is an autosomal recessive inherited disorder of hepatic copper metabolism resulting in liver disease and/or neuropsychiatric disease. The diagnosis of neurological disease is straightforward if the following symptoms are present: Kayser-Fleischer rings, typical neurological symptoms and low serum ceruloplasmin levels. The diagnosis is more complex in patients presenting with liver diseases. None of the commonly used parameters alone allows a diagnosis with certainty. A combination of various laboratory parameters is necessary to firmly establish the diagnosis. In the future, limited mutation analysis may play an important diagnostic role. Recently, a group of international experts has proposed a score based on a variety of tests and clinical symptoms. The validity of this score needs to be assessed prospectively. Treatment requires life-long administration of copper chelators (d-penicillamine, trientine). A frequently used alternative is zinc. None of these treatments has been tested by prospective randomized controlled studies. Liver transplantation is reserved for severe or treatment-resistant cases with advanced liver disease, whilst experience with refractory neuropsychiatric disease is limited. [References: 57]",Antioxidants/tu [Therapeutic Use];Chelating Agents/tu [Therapeutic Use];Genetic Testing;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver Transplantation;Pedigree;Zinc/tu [Therapeutic Use];0 (Antioxidants);0 (Chelating Agents);J41CSQ7QDS (Zinc),"Ferenci, P.",2004,Jan 15,,0,0,
445,Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's disease,"BACKGROUND: There are only a few reports regarding the fertility and outcome of pregnancy in Wilson's disease (WD) and none from India. The authors in this study discuss various aspects of fertility in 16 women with WD. METHODS: Retrospective analysis of data from a large cohort of WD, being followed at a tertiary care center. RESULTS: Sixteen patients had conceived on 59 occasions with 30 successful pregnancies, 24 spontaneous abortions, 2 medical terminations of pregnancy and 3 still births. Diagnosis of WD was established after conception in 10 presymptomatic patients while six patients were already on treatment. Among these 16 patients, 9 had history of spontaneous abortions and 12 had successful pregnancies. None of the clinical features of WD changed during pregnancy, with or without treatment. All the 30 babies were full-term and delivered healthy. CONCLUSION: Recurrent abortions are common especially in women with untreated Wilson's disease. However, successful pregnancies and uneventful full-term delivery may occur in mothers of WD on treatment and in undiagnosed, undetected presymptomatic patients. Pregnancy does not seem to have adverse effect on the clinical course of Wilson's disease. Teratogenecity was not seen in the present series with low-dose penicillamine and zinc sulphate.","Abortion, Induced;*Abortion, Spontaneous/pp [Physiopathology];Adolescent;Adult;Cohort Studies;Female;*Fertilization/ph [Physiology];Follow-Up Studies;Hepatolenticular Degeneration/cl [Classification];Hepatolenticular Degeneration/ep [Epidemiology];*Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;Middle Aged;Pregnancy;*Pregnancy Outcome","Sinha, S.;Taly, A. B.;Prashanth, L. K.;Arunodaya, G. R.;Swamy, H. S.",2004,Jan 15,,0,0,
446,The nucleotide-binding domain of the Zn2+-transporting P-type ATPase from Escherichia coli carries a glycine motif that may be involved in binding of ATP,"In P-type ATPases, the nucleotide-binding (N) domain is located in the middle of the sequence which folds into the phosphorylation (P) domain. The N domain of ZntA, a Zn2+-translocating P-type ATPase from Escherichia coli, is approx. 13% identical with the N domain of sarcoplasmic reticulum Ca2+-ATPase. None of the Ca2+-ATPase residues involved in binding of ATP are found in ZntA. However, the sequence G503SGIEAQV in the N domain of ZntA resembles the motif GxGxxG, which forms part of the ATP-binding site in protein kinases. This motif is also found in Wilson disease protein where several disease mutations cluster in it. In the present work, we have made a set of disease mutation analogues, including the mutants G503S (Gly503-->Ser), G505R and A508F of ZntA. At low [ATP], these mutant ATPases are poorly phosphorylated. The phosphorylation defect of the mutants G503S and G505R can, however, be partially (G503S) or fully (G505R) compensated for by using a higher [ATP], suggesting that these mutations lower the affinity for ATP. In all three mutant ATPases, phosphorylation by P(i) has become less sensitive to the presence of ATP, also consistent with the proposal that the Gly503 motif plays a role in ATP binding. In order to test this hypothesis, we have modelled the N domain of ZntA using the sarcoplasmic reticulum Ca2+-ATPase structure as a template. In the model, the Gly503 motif, as well as the residues Glu470 and His475, are located in the proximity of the ATP-binding site. In conclusion, the mutagenesis data and the molecular model are consistent with the idea that the two loops carrying the residues Glu470, His475, Gly503 and Gly505 play a role in ATP binding and activation.","*Adenosine Triphosphatases/ch [Chemistry];Adenosine Triphosphatases/ge [Genetics];*Adenosine Triphosphatases/me [Metabolism];*Adenosine Triphosphate/me [Metabolism];Adenosine Triphosphate/pd [Pharmacology];Amino Acid Motifs;Amino Acid Sequence;Binding Sites;*Escherichia coli/en [Enzymology];Glycine/ge [Genetics];*Glycine/ph [Physiology];Histidine/ge [Genetics];Histidine/ph [Physiology];Kinetics;Models, Molecular;Molecular Sequence Data;Mutation;Nucleotides/me [Metabolism];Phosphorylation;Protein Structure, Tertiary;Sequence Alignment;Zinc/pd [Pharmacology];0 (Nucleotides);4QD397987E (Histidine);8L70Q75FXE (Adenosine Triphosphate);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-1 (Zn(II)-translocating P-type ATPase);J41CSQ7QDS (Zinc);TE7660XO1C (Glycine)","Okkeri, J.;Laakkonen, L.;Haltia, T.",2004,Jan 01,https://dx.doi.org/10.1042/BJ20030740,0,0,
447,Results of treatment of Wilson's disease--own observations,"BACKGROUND: Causative treatment of genetically determined Wilson's disease (WD) has been impossible so far, although gene therapy could be real in the future. Nowadays the principle of treatment is the elimination of the excess of easily mobilized copper, bound by chelating agents, the most important of which is d-penicillamine, through the kidneys. Blocking of the intestinal absorption of copper by administration of zinc preparations, which additionally induce hepatic metallothionein synthesis, is also possible. The aim of our study was to present own observations and results of treatment of Wilson's disease. MATERIAL/METHODS: During the last 16 years, we have observed 33 patients aged 13-60 (mean age 27 years) with various forms of WD. The studied group consisted of 11 females and 21 males, admitted to hospital or seen at the Specialistic Outpatient Department of Hepatology with various diagnoses. In addition to standard laboratory tests, the levels of ceruloplasmin, serum and urine copper, as well as the activity of some hepatic enzymes, proteins and HBV/HCV infection markers were determined. The patients were also examined by a neurologist and an ophthalmologist, with psychiatric consultation if necessary. Taking into account the overall clinical presentation, the patients were divided into the following groups according to the form of the disease: fulminant, acute, hepatic, hepatic with neurological and psychiatric symptoms, neuropsychiatric, asymptomatic. RESULTS: All the patients were initially treated with d-penicillamine. In most of them, no side effects were observed. The treatment was continued according to the levels of copper excreted with urine (for 10 years at the longest). After obtaining clinical improvement with reduced amount of copper excreted with 24-h urine, we tapered d-penicillamine doses or even discontinued the drug, introducing zinc preparations. In asymptomatic carriers, zinc preparations were used throughout the period of treatment. CONCLUSIONS: Early institution of chelation treatment is associated with good prognosis both in hepatic and neurological forms of WD. Zinc preparations are effective and safe in neurological and oligosymptomatic forms of the disease.",Adolescent;Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/px [Psychology];Humans;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Jablonska-Kaszewska, I.;Drobinska-Jurowiecka, A.;Dabrowska, E.;Trocha, H.",2003,Aug,,0,1,
448,Treatment of Wilson's disease,"On the basis of literature review and own experience we presented the method of treatment of Wilson's disease. Causative treatment has been impossible so far, although gene therapy could be real in the future. Nowadays the principle of treatment is the elimination of the excess of easily mobilized copper by chelating agents or blocking the intestinal absorption of copper. Chelation therapy, aimed at mobilizing copper from the affected organs and promoting its excretion in the urine or stool is the most important. The major chelating agent is d-penicillamine, which is quite effective but not without some side effects. Alternative chelating agents such as trientine and tetrathiomolybdate have also been successfully employed. Zinc salts are also of therapeutic value. They promote copper excretion by inducing the synthesis of metallothionein in the intestine, thereby blocking copper absorption from the gut. Zinc salts have almost no side effects. They cannot be used as an initial treatment, but are very effective for maintenance therapy. The chelation therapy is ineffective in patients with acute liver failure with encephalopathy and hemolysis. In these cases, liver transplantation is the only hope for survival. Liver transplantations in patients with dominating psychoneurological symptoms are open to discussion.",Chelating Agents/ch [Chemistry];*Chelating Agents/tu [Therapeutic Use];Copper/ch [Chemistry];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/su [Surgery];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation;0 (Chelating Agents);789U1901C5 (Copper),"Jablonska-Kaszewska, I.;Dabrowska, E.;Drobinska Jurowiecka, A.;Falkiewicz, B.",2003,Aug,,0,0,
449,Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic decompensation presentation with trientine and zinc,"We have treated 9 patients who presented with hepatic decompensation resulting from Wilson's disease with a combination of trientine and zinc, generally for at least 4 months, followed by transition to zinc maintenance therapy. All of these patients had hypoalbuminemia, all but 1 had hyperbilirubinemia, and 7 had ascites. All of these patients would have been candidates for liver transplantation on the basis of their initial Child-Turcotte-Pugh (CTP) scores. The minimal listing criteria for transplant candidates is a score greater than 7. Eight of the 9 patients had demonstrated a CTP score of 10 or higher. The other scoring system that has been used in Wilson's disease to determine need for transplantation is the prognostic index of Nazer, in which a score over 6 indicates that the patient is unlikely to survive without a transplant if treated with penicillamine. Two of our patients had Nazer scores higher than 6. With our medical therapy, all 9 of these patients have recovered normal liver function as reflected by normalization of their CTP scores to 5. Because of coexisting neurologic disease, 1 of our 9 patients was initiated on a neurologic protocol and by chance randomized to receive tetrathiomolybdate (TM) and zinc after 2 weeks of trientine/zinc treatment. This patient's liver function recovered much more rapidly than did that of the other 8 patients, all of whom were treated with trientine/zinc, suggesting that TM therapy offers a further advantage. In summary, we were able to take 9 patients who presented with liver failure -8 of whom had CTP scores indicating a potential need for liver transplantation and 2 of whom had Nazer prognostic scores indicating that they were not likely to survive if treated only with penicillamine - and treat them medically, with recovery in all 9. We believe the trientine/zinc combination therapy should be the standard for initial treatment of liver failure in Wilson's disease because its efficacy is equal or slightly superior to that of penicillamine and because it has a much lower incidence of side effects. Moreover, TM warrants study to determine whether therapy for hepatic Wilson's disease can be further improved.","Adult;Drug Therapy, Combination;Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Failure/dt [Drug Therapy];Male;*Trientine/ad [Administration & Dosage];*Zinc/ad [Administration & Dosage];J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Askari, F. K.;Greenson, J.;Dick, R. D.;Johnson, V. D.;Brewer, G. J.",2003,Dec,https://dx.doi.org/10.1016/S0022-2143(03)00157-4,0,1,
450,Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome),"We report a girl who had Hirschsprung disease in association with distinct facial appearance, microcephaly, agenesis of the corpus callosum and mental retardation (Mowat-Wilson syndrome). Mutation analysis of the zinc finger homeo box 1 B (ZFHX1 B) gene revealed a de novo 7 bp deletion (TGGCCCC) at nucleotide 1773 (1773 delTGGCCCC) resulting in a frameshift and leading to a termination codon at amino acid residue 604 (604 X) in exon 8 C. The zinc finger homeo box 1 B (Smad interacting protein-1) is a transcription corepressor of Smad target genes with functions in the patterning of neural crest derived cells, CNS, and midline structures. Mutations in ZFHX1 B can lead to neurological disorders in addition to dysmorphic features, megacolon, and other malformations.","*Abnormalities, Multiple/ge [Genetics];*Agenesis of Corpus Callosum;Female;*Frameshift Mutation;*Hirschsprung Disease/ge [Genetics];*Homeodomain Proteins/ge [Genetics];Humans;Infant;Infant, Newborn;Intellectual Disability/ge [Genetics];*Microcephaly/ge [Genetics];*Repressor Proteins/ge [Genetics];Syndrome;0 (Homeodomain Proteins);0 (Repressor Proteins);0 (ZEB2 protein, human)","Sztriha, L.;Espinosa-Parrilla, Y.;Gururaj, A.;Amiel, J.;Lyonnet, S.;Gerami, S.;Johansen, J. G.",2003,Dec,https://dx.doi.org/10.1055/s-2003-44671,0,0,
451,Transient fetal myelosuppressive effect of D-penicillamine when used in pregnancy,"Normal fertility is sustained by progress in the medical therapy of Wilson's disease; however, pregnancy complications are encountered more frequently. The mother we present is a Wilson's disease patient who had been compliant with D-penicillamine for the preceding 13 years. She was admitted with unplanned pregnancy at the 16th gestational week. The dose of D-penicillamine could be reduced to 600 mg/d related to the underlying disease. Pregnancy ended with premature labor and delivery at the 29-30th weeks. The baby experienced type I respiratory distress and was treated by surfactant and mechanical ventilation. Neutropenia and leucopenia were documented at 6th postnatal hours. The baby showed neutropenia and leucopenia for 5 days and resolving without any further therapy. Intrauterine D-penicillamine was suspected to cause transient neonatal myelosuppression.","*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Female;*Fetal Diseases/ci [Chemically Induced];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;*Leukopenia/ci [Chemically Induced];*Neutropenia/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Pregnancy;Pregnancy Complications/dt [Drug Therapy];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Yalaz, M.;Aydogdu, S.;Ozgenc, F.;Akisu, M.;Kultursay, N.;Yagci, R. V.",2003,Dec,,0,0,
452,Current and future therapy in haemochromatosis and Wilson's disease,"There have been several new developments in the treatment of iron and copper overload disorders, such as haemochromatosis, thalassaemia and Wilson's disease. Clinical trials of orally administered iron chelators, both as monotherapy and in combination with deferoxamine, are in progress around the world. Several new chelators are now being introduced in clinical trials. Future therapies for iron overload may comprise of oral iron binding agents capable of preventing dietary iron absorption from the diet. The characterisation of specific iron transporters such as the divalent metallic transporter and ferroportin may hold promise for the development of 'smart' compounds capable of blocking iron transport. Several new agents are now available for the management of Wilson's disease, including trientine, zinc and tetrathiomolybdate. This review, will discuss the pathogenesis, and current and future therapies for iron and copper overload disorders. [References: 114]","Administration, Oral;Copper/me [Metabolism];Drug Therapy, Combination;*Hemochromatosis/dt [Drug Therapy];Hemochromatosis/ge [Genetics];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Iron/me [Metabolism];Iron Chelating Agents/ad [Administration & Dosage];Iron Chelating Agents/pd [Pharmacology];Iron Chelating Agents/tu [Therapeutic Use];0 (Iron Chelating Agents);789U1901C5 (Copper);E1UOL152H7 (Iron)","Murray, K. F.;Lam, D.;Kowdley, K. V.",2003,Dec,https://dx.doi.org/10.1517/14656566.4.12.2239,0,0,
453,Bridging use of plasma exchange and continuous hemodiafiltration before living donor liver transplantation in fulminant Wilson's disease,"A 15-year-old girl presented with acute hepatic failure showing ascites and hepatic encephalopathy, accompanied by hemolytic anemia. She was diagnosed as having fulminant Wilson's disease (FWD). Plasma exchange (PE), continuous hemodiafiltration (CHDF) and D-penicillamine administration were started immediately. Copper [24,000 microg] was removed by PE and CHDF over three days, which relieved the jaundice and the consciousness disorder. A successful liver transplant followed. FWD progresses rapidly and often liver transplantation is the only possible therapy. In this case, PE and CHDF were an effective therapy bridge until liver transplantation.",Adolescent;Chelating Agents/tu [Therapeutic Use];Female;*Hemodiafiltration/mt [Methods];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/su [Surgery];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Failure/et [Etiology];Liver Failure/su [Surgery];*Liver Failure/th [Therapy];*Liver Transplantation;*Living Donors;Penicillamine/tu [Therapeutic Use];*Plasma Exchange/mt [Methods];Preoperative Care;Treatment Outcome;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Nagata, Y.;Uto, H.;Hasuike, S.;Ido, A.;Hayashi, K.;Eto, T.;Hamakawa, T.;Tanaka, K.;Tsubouchi, H.",2003,Oct,,0,0,
454,Status epilepticus in a case with wilson's disease during D-pencillamine treatment,,Adult;*Cerebral Cortex/pa [Pathology];Electroencephalography;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Male;*Penicillamine/ae [Adverse Effects];*Status Epilepticus/ci [Chemically Induced];GNN1DV99GX (Penicillamine),"Turk-Boru, U.;Kocer, A.;Alp, R.;Gumus, M.;Gumus, M.",2003,Aug 09,https://dx.doi.org/2003/31/smw-10286,0,0,
455,Wilson disease,"Wilson disease is a rare disorder of copper metabolism that results in accumulation of copper in the liver and subsequently in other organs, mainly the central nervous system and the kidneys. Advances in the diagnosis and treatment of Wilson disease are discussed, with the emphasis that this is a disease of children, adolescents, and young adults. The myriad manifestations of Wilson disease make its diagnosis dependent on a high index of suspicion, and determination of its genetic background is helping to elucidate the genotype-phenotype correlation and the diversity of presentations. Treatment of Wilson disease has progressed from chelation therapy using D-penicillamine and trientine to the more recent use of zinc and finally to the establishment of liver transplantation as an urgent but excellent modality for fulminant presentation. The evolution of Wilson disease from a uniformly fatal disease to an eminently treatable disease during the past century is an example of the remarkable advances of modern medicine. [References: 62]",Adenosine Triphosphatases/ai [Antagonists & Inhibitors];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation;Molybdenum/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 3-6-1 (Adenosine Triphosphatases);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"El-Youssef, M.",2003,Sep,https://dx.doi.org/10.1016/S0025-6196(11)62937-6,0,0,
456,[Nephrolithiasis as an initial clinical manifestation of Wilson-Konovalov disease],,"Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Diagnosis, Differential;Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Kidney Calculi/et [Etiology];Liver Cirrhosis/et [Etiology];Male;Middle Aged;Obesity/co [Complications];Penicillamine/tu [Therapeutic Use];Treatment Outcome;0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Rakhimova, OIu;Rozina, T. P.;Ignatova, T. M.",2003,,,0,0,
457,A case report on Wilson's disease,"A case of Wilson's disease, a rare autosomal recessive disorder of copper metabolism is reported here. The patient was presented with the difficulty in speech and writing for 4 years and also on walking for 1 year. He also noticed difficulty to perform any work by hands for 6 months. He had splenomegaly and bilateral gynaecomastia. His speech was low volume slurred and monotonous, muscle tone was mildly increased, and gait was limping. Slit lamp examination of eye revealed bilateral Kayser-Fleischer ring with normal visual acuity. Investigations revealed low serum albumin(26 gram/L), increased alanine trans-aminase ( A.L.T=57 U/L). Ultrasonogram of hepatobiliary system revealed coarse hepatic tissue echotexture with splenomegaly. Liver scan showed slightly nonuniform radiotracer distribution in the liver, there was slight increased bony uptake. Serum caeruloplasmin level was 11.51 mg/dl. 24 hours urinary copper excretion was 150 microgram per day. Liver biopsy revealed cirrhotic change. Now he was advised for taking copper chelating agent (penicillamine) in a dose of 1 gram/day.",Adolescent;Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];Physical Examination/mt [Methods];0 (Chelating Agents);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Rahman, S.;Siddiqui, N. I.;Paul, G. K.;Sarker, C. B.;Rahman, K. M.",2003,Jul,,0,0,
458,[From gene to disease; Wilson disease: copper storage due to mutations in ATP7B],,*Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];*Copper/me [Metabolism];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Mutation;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);GNN1DV99GX (Penicillamine),"Hoogenraad, T. U.",2003,Jul 12,,0,0,
459,The story of penicillamine: a difficult birth,,"Adult;*Antirheumatic Agents/ch [Chemistry];*Antirheumatic Agents/hi [History];Antirheumatic Agents/tu [Therapeutic Use];*Chelating Agents/ch [Chemistry];*Chelating Agents/hi [History];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];History, 20th Century;Humans;Liver/me [Metabolism];Liver/pp [Physiopathology];*Penicillamine/ch [Chemistry];*Penicillamine/hi [History];Penicillamine/tu [Therapeutic Use];*Pharmacology/hi [History];United Kingdom;0 (Antirheumatic Agents);0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Walshe, J. M.",2003,Aug,https://dx.doi.org/10.1002/mds.10458,0,0,
460,Neurologic deterioration in a child with Wilson's disease on penicillamine therapy,Penicillamine is the standard therapy for Wilson's disease in children. We report an 8-year-old-girl with liver disease due to Wilson's disease who developed extrapyramidal symptoms following administration of penicillamine. Symptoms resolved within 20 hours of stopping the drug but recurred within 24 hours when gradually increasing small doses were recommenced.,"*Chelating Agents/ae [Adverse Effects];Child;Dose-Response Relationship, Drug;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Neurodegenerative Diseases/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Syndrome;0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Paul, A. C.;Varkki, S.;Yohannan, N. B.;Eapen, C. E.;Chandy, G.;Raghupathy, P.",2003,May-Jun,,0,0,
461,Clinical presentation and treatment of Wilson's disease: a single-centre experience,"Thirty patients with Wilson's disease (WD) were observed at a movement disorder clinic between 1970 and 2000. Disease onset was at the mean age (SD) of 14.5 (+/-5.9) years. Presentation with hepatic disease occurred in 12 of 30 patients and with neurologic disease in 15. Three patients were asymptomatic at the time of diagnosis. The mean (SD) delay to diagnosis was 5.9 (+/-5.7) years. Five patients diagnosed in an advanced stage of disease died before initiating treatment. Eighteen patients were followed and treated with D-penicillamine alone or in combination with zinc sulphate. Treatment improved most of neurological symptoms. Dystonic postures, behavioural disturbances and dysarthria were the most resistant neurological signs. 'Pseudo-sclerotic' neurologic involvement predicted a good outcome, whereas hepatic onset and 'classic' neurologic involvement were associated with a poorer prognosis. Two of the 18 treated patients died of hepatic failure due to voluntary discontinuation of therapy. Both D-penicillamine and zinc sulphate were well tolerated. No teratogenic effect of D-penicillamine was observed throughout 5 pregnancies. Our results suggest that D-penicillamine or a combination of D-penicillamine and zinc sulphate is a safe and effective long-term treatment in patients with WD. Copyright 2003 S. Karger AG, Basel","Adolescent;Adult;Brain/de [Drug Effects];Brain/pa [Pathology];Child;Child, Preschool;Drug Therapy, Combination;*Dysarthria/di [Diagnosis];Dysarthria/dt [Drug Therapy];Dysarthria/mo [Mortality];*Dystonia/di [Diagnosis];Dystonia/dt [Drug Therapy];Dystonia/mo [Mortality];Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/mo [Mortality];Humans;Long-Term Care;Magnetic Resonance Imaging;Male;*Mental Disorders/di [Diagnosis];Mental Disorders/dt [Drug Therapy];Mental Disorders/mo [Mortality];Neurologic Examination/de [Drug Effects];Penicillic Acid/ae [Adverse Effects];*Penicillic Acid/aa [Analogs & Derivatives];Penicillic Acid/tu [Therapeutic Use];Pregnancy;Retrospective Studies;Survival Rate;Treatment Outcome;Zinc Sulfate/ae [Adverse Effects];Zinc Sulfate/tu [Therapeutic Use];34138-28-8 (penicillamide);7733-02-0 (Zinc Sulfate);ONL14K3AFD (Penicillic Acid)","Pellecchia, M. T.;Criscuolo, C.;Longo, K.;Campanella, G.;Filla, A.;Barone, P.",2003,,https://dx.doi.org/70858,0,1,
462,Zinc treatment prevents lipid peroxidation and increases glutathione availability in Wilson's disease,"Oxidative and reductive mechanisms are important in Wilson's disease. In this study, we sought to evaluate tissue levels of glutathione and cysteine, an important detoxification system, and of malondialdehyde, a marker of lipoperoxidation, in patients with Wilson's disease receiving penicillamine or zinc treatment, in comparison with patients with chronic liver disease of different origin. Concentrations of cysteine, reduced/oxidized glutathione, malondialdehyde, zinc, and copper were determined (with the use of high-pressure liquid chromatography, fluorimetry and atomic-absorption spectrophotometry) in liver-biopsy specimens from 24 patients with Wilson's disease (18 treated with zinc, 6 with penicillamine), 34 patients with chronic viral hepatitis, and 10 patients with alcoholic liver disease. In patients with Wilson's disease, the concentration of reduced glutathione was lower than that in patients with viral hepatitis and as high as that in subjects with alcoholic liver damage. The cysteine level was significantly lower than those in the control groups, and the percentage of oxidized glutathione/total glutathione was higher than that in viral or alcoholic disease. Malondialdehyde levels were low, but when zinc- and penicillamine-treated patients were considered separately, only the former had low malondialdehyde levels. Zinc-treated patients had higher concentrations of reduced glutathione and a lower percentage of oxidized glutathione. In summary, patients with Wilson's disease have relevant glutathione depression, with low levels of reduced glutathione and cysteine and high concentrations of oxidized glutathione: This is prevented by zinc administration, which inhibits lipid peroxidation and increases glutathione availability.","Adolescent;Adult;Aged;Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Female;*Glutathione/me [Metabolism];Hepatitis C/pa [Pathology];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;*Lipid Peroxidation/de [Drug Effects];Liver/pa [Pathology];Liver Diseases, Alcoholic/pa [Pathology];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Zinc/me [Metabolism];*Zinc Sulfate/pd [Pharmacology];*Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GAN16C9B8O (Glutathione);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Farinati, F.;Cardin, R.;D'Inca, R.;Naccarato, R.;Sturniolo, G. C.",2003,Jun,https://dx.doi.org/10.1016/S0022-2143(03)00027-1,0,0,
463,Antiangiogenic therapy through copper chelation,"As new compounds are being evaluated for use in clinical trials involving antiangiogenic therapies, two important factors must be considered. Independent of clinical efficacy, the potential drug must be cost-effective and have reasonable ease of production. The compound endostatin (Entremed, Inc.) has recently completed two Phase I trials with minimal toxicity to the patients treated [1,2]. However, due to the difficulty and expense of producing large quantities of a recombinant protein, Entremed Inc. has experienced financial difficulties [3]. As this company's fate indicates, a drug must not only be clinically effective, but must also possess reasonable production economics. Another interesting component of compound development is selectivity. Highly selective antiangiogenic compounds such as the tyrosine kinase inhibitor SU-5416 are being replaced by less selective compounds such as SU-6668, which acts on a broader spectrum of tyrosine kinase receptors [4]. This move towards using less selective antiangiogenic compounds is based on preclinical models that demonstrate both better clinical efficacy when using less specific molecules and low response rates from the more selective compounds. With the aim of further examining broadly-acting antiangiogenic agents, the authors are currently evaluating new classes of agents that preferentially bind copper and inhibit angiogenesis. Copper has been known to be a significant target for antiangiogenic therapy for a number of years [5]. Recently, through the use of molecular techniques, the target enzymes that utilise copper as a cofactor are being elucidated. This review will describe the historical use of anticopper therapy for the treatment of Wilson's disease and evaluate some of the new anticopper compounds currently under consideration for use in antiangiogenic therapy. [References: 45]","Angiogenesis Inhibitors/pd [Pharmacology];*Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];*Chelation Therapy;*Copper;Corneal Neovascularization/dt [Drug Therapy];Cyclohexylamines/pd [Pharmacology];Cyclohexylamines/tu [Therapeutic Use];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/pd [Pharmacology];Molybdenum/tu [Therapeutic Use];Neoplasms/bs [Blood Supply];Neoplasms/dt [Drug Therapy];Neovascularization, Pathologic/dt [Drug Therapy];Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Pyridines/pd [Pharmacology];Pyridines/tu [Therapeutic Use];Rabbits;Trientine/pd [Pharmacology];Trientine/tu [Therapeutic Use];0 (Angiogenesis Inhibitors);0 (Chelating Agents);0 (Cyclohexylamines);0 (Pyridines);0 (tachpyr);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Sproull, M.;Brechbiel, M.;Camphausen, K.",2003,Jun,https://dx.doi.org/10.1517/14728222.7.3.405,0,0,
464,"Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation","The need for agents to lower body copper in Wilson's disease, a disease which results from copper toxicity has been the driving force for the development of the effective anticopper drugs penicillamine, trientine, zinc, and now tetrathiomolybdate (TM). Because of its rapid action, potency, and safety, TM is proving to be a very effective drug for initial treatment of acutely ill Wilson's disease patients. Beyond this, TM has antiangiogenic effects, because many proangiogenic cytokines require normal levels of copper. This has led to use of TM in cancer, where it is generally effective in animal tumor models, and has shown efficacy in preliminary clinical studies. Most recently, it has been found that TM has antifibrotic and antiinflammatory effects through inhibition of profibrotic and proinflammatory cytokines. [References: 82]",*Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;Chelation Therapy;*Copper/me [Metabolism];Cytokines/me [Metabolism];*Fibrosis/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Inflammation/me [Metabolism];*Molybdenum/tu [Therapeutic Use];0 (Angiogenesis Inhibitors);0 (Cytokines);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Brewer, G. J.",2003,Jan-Mar,,0,0,
465,D-penicillamine and plasmapheresis in acute liver failure secondary to Wilson's disease,"We report a case of a 19-year-old woman with acute liver failure, Coombs negative hemolytic anemia, and renal failure as initial manifestations of Wilson disease with recovery following medical treatment. The clinical picture and low serum transaminase and alkaline phosphatase levels gave us a clue to suspect Wilson disease and to initiate plasmapheresis and D-penicillamine soon after admission. The serum and urinary copper levels were elevated with low serum ceruloplasmin. We proceeded to ambulatory follow-up with medical treatment with D-penicillamine. A few months later, during the course of a laparoscopic cholecystectomy because of symptomatic gallstone disease, a liver biopsy sample was obtained that showed histological liver fibrosis and strongly elevated levels of liver tissue copper.","Adult;Anemia, Hemolytic/co [Complications];Biopsy;Ceruloplasmin/an [Analysis];*Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Copper/ur [Urine];Female;Follow-Up Studies;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/ur [Urine];Humans;Liver/pa [Pathology];Liver Failure, Acute/dt [Drug Therapy];*Liver Failure, Acute/et [Etiology];*Liver Failure, Acute/th [Therapy];*Penicillamine/tu [Therapeutic Use];*Plasmapheresis;Time Factors;0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Rodriguez Farina, E.;Tremosa Llurba, G.;Xiol Quingles, X.;Lores Obradors, A.;Castellote Alonso, J.;Gornals Soler, J. B.;Lopez Nunez, C.",2003,Jan,,0,0,
466,Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease,"BACKGROUND: The potential for therapy for Wilson disease (WD) emphasizes the importance of presymptomatic diagnosis in families with WD (WD families). OBJECTIVES: To investigate the feasibility of presymptomatic DNA diagnosis and evaluate the efficacy of zinc sulfate therapy in WD families. METHODS: Seventy-eight clinically unaffected siblings were studied from 51 unrelated WD families that were ascertained by affected individuals. The diagnosis in presymptomatic patients was established by a combination of direct mutational analysis and haplotype analysis with 3 short tandem repeat markers. The presymptomatic patients were treated with 50 mg of elemental zinc sulfate twice a day from the time of molecular diagnosis and followed up for 3 to 5 years. RESULTS: Of the 78 siblings, 17 were diagnosed as presymptomatic patients. Kayser-Fleischer rings were absent in 7 and faint in 4 of the 17 presymptomatic patients. The serum ceruloplasmin values gradually increased and 24-hour urinary copper values gradually diminished during zinc therapy, which indicate effective control of copper metabolism. None of the siblings developed clinical symptoms of WD or adverse effects from zinc therapy. CONCLUSION: We conclude that presymptomatic DNA diagnosis and zinc therapy are effective treatment of patients with WD.","Adolescent;Adult;Asian Continental Ancestry Group;Ceruloplasmin/me [Metabolism];Child;Copper/ur [Urine];Female;Follow-Up Studies;Haplotypes;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;Polymorphism, Single-Stranded Conformational;*Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin)","Wu, Z. Y.;Lin, M. T.;Murong, S. X.;Wang, N.",2003,May,https://dx.doi.org/10.1001/archneur.60.5.737,0,0,
467,Early occurrence of hypertransaminasemia in a 13-month-old child with Wilson disease,,*Alanine Transaminase/bl [Blood];*Aspartate Aminotransferases/bl [Blood];Biopsy;Ceruloplasmin/an [Analysis];Copper/bl [Blood];Copper/ur [Urine];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/en [Enzymology];Hepatolenticular Degeneration/pa [Pathology];Humans;Infant;Liver/en [Enzymology];Liver/pa [Pathology];Zinc Sulfate/tu [Therapeutic Use];7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase),"Iorio, R.;D'Ambrosi, M.;Mazzarella, G.;Varrella, F.;Vecchione, R.;Vegnente, A.",2003,May,,0,0,
468,Wilson's disease: the importance of measuring serum caeruloplasmin non-immunologically,"Wilson's disease should be considered as a possible diagnosis in any child, adolescent or young adult with liver damage without other explanation, especially when haemolysis is present. However, it may also present in adolescents or young adults with neurological signs confined to the motor system. The first diagnostic screening test is the estimation of the serum caeruloplasmin and total serum copper concentrations, with calculation of the serum non-caeruloplasmin-bound ('free') copper. Serum caeruloplasmin, which contains copper, is best determined by measurement of its oxidase activity, as the immunonephelometric method measures both caeruloplasmin and the biologically inactive apo-form. Diagnosis may be confirmed by an elevated urinary copper excretion. All close relatives of an identified patient must be screened and, where doubt persists, investigation of the Wilson's gene at chromosome 13q14.3 can be employed. Lifelong follow-up studies are best conducted in a specialist centre. Compliance with chelating therapy (penicillamine or trientine) or administration of the metal antagonist tetrathiomolybdate or zinc is monitored by determination of the serum 'free' copper, which should be maintained at or near 1.6 micromol/L (10 microg/100 mL). Side-effects of therapy are detected by the estimation of urinary total protein, full blood count and erythrocyte sedimentation rate, clotting factors and liver function tests. [References: 35]","*Ceruloplasmin/bi [Biosynthesis];*Chemistry, Clinical/mt [Methods];Copper/bl [Blood];Female;*Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;Male;Microsatellite Repeats;Oxidoreductases/me [Metabolism];Pedigree;789U1901C5 (Copper);EC 1 (Oxidoreductases);EC 1-16-3-1 (Ceruloplasmin)","Walshe, J. M.;Clinical Investigations Standing Committee of the Association of Clinical, Biochemists",2003,Mar,https://dx.doi.org/10.1258/000456303763046021,0,0,
469,Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy,"BACKGROUND: It is unclear what anticopper drug to use for patients with Wilson disease who present with neurologic manifestations because penicillamine often makes them neurologically worse and zinc is slow acting. OBJECTIVE: To evaluate the frequency of neurologic worsening and drug adverse effects with ammonium tetrathiomolybdate. DESIGN: Open-label study of 55 untreated patients (22 of them new) presenting with neurologic Wilson disease treated with tetrathiomolybdate varying from 120 to 410 mg/d for 8 weeks and then followed up for 3 years. Neurologic function was assessed with scored neurologic and speech tests. SETTING: A university hospital referral setting. PATIENTS: All untreated, newly diagnosed patients with neurologic Wilson disease. INTERVENTION: Treatment with tetrathiomolybdate. MAIN OUTCOME MEASURES: Neurologic function was evaluated by neurologic and speech examinations. Drug adverse effects were evaluated by complete blood cell counts and biochemical measures. RESULTS: Only 2 (4%) of 55 patients treated with tetrathiomolybdate showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers are higher than in the original 33 patients and appear to be due primarily to a more rapid dose escalation. CONCLUSIONS: Tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur.",Adult;Child;*Enzyme Inhibitors/ad [Administration & Dosage];Enzyme Inhibitors/ae [Adverse Effects];Female;Follow-Up Studies;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Molybdenum/ad [Administration & Dosage];Molybdenum/ae [Adverse Effects];Nervous System Diseases/di [Diagnosis];Nervous System Diseases/dt [Drug Therapy];Nervous System Diseases/et [Etiology];Neurologic Examination;Treatment Outcome;*Zinc/ad [Administration & Dosage];0 (Enzyme Inhibitors);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc),"Brewer, G. J.;Hedera, P.;Kluin, K. J.;Carlson, M.;Askari, F.;Dick, R. B.;Sitterly, J.;Fink, J. K.",2003,Mar,,0,1,
470,Tetrathiomolybdate causes formation of hepatic copper-molybdenum clusters in an animal model of Wilson's disease,"Wilson's disease is an autosomal recessive human illness in which large quantities of copper accumulate in various organs, including the brain and the liver. If left untreated, it results in hepatitis, neurological complications, and death. Long-Evans Cinnamon (LEC) rats have a homologous mutation to Wilson's disease and thus provide an animal model. Liver lysosomes from tetrathiomolybdate-treated LEC rats were isolated and analyzed by Cu and Mo K-edge X-ray absorption spectroscopy. The lysosomes contained a Cu-Mo-S cluster in which the Mo is coordinated by four sulfurs at 2.24 A with approximately three copper neighbors at 2.70 A. Each Cu is coordinated to 3-4 sulfurs at 2.28 A with approximately one Mo neighbor at 2.70 A. These results indicate the formation of a biologically novel molybdenum-copper-sulfur cluster.","Animals;Copper/ch [Chemistry];*Copper/me [Metabolism];Disease Models, Animal;Fourier Analysis;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/ch [Chemistry];Liver/de [Drug Effects];Liver/me [Metabolism];Lysosomes/de [Drug Effects];Lysosomes/me [Metabolism];Molecular Structure;Molybdenum/ch [Chemistry];*Molybdenum/me [Metabolism];*Molybdenum/pd [Pharmacology];Rats;Rats, Inbred LEC;Spectrometry, X-Ray Emission/mt [Methods];Sulfur/ch [Chemistry];Sulfur/me [Metabolism];70FD1KFU70 (Sulfur);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate)","George, G. N.;Pickering, I. J.;Harris, H. H.;Gailer, J.;Klein, D.;Lichtmannegger, J.;Summer, K. H.",2003,Feb 19,https://dx.doi.org/10.1021/ja029054u,0,0,
471,[Peripheral nociceptin levels in Wilson disease],"Plasma level of nociceptin, the endogenous agonists of orphaninFQ/OP4 receptor was found to be significantly elevated in Wilson's disease patients (14.87 +/- 2.44 pg/ml +/- SD, p < 0.001, n = 21) compared to age-matched healthy controls (9.18 +/- 1.63 pg/ml +/- SD, n = 25). Wilson's disease is an autosomal recessive disorder caused by mutation of the gene ATP7B leading to toxic copper accumulation mainly in the liver and brain and in other organs such as, kidney and cornea. Measurements were performed by 125I-radioimmunoassay. Neither sex differences nor correlation between plasma nociceptin levels and liver function test results were found in Wilson's disease patients. It is suggested that significantly elevated plasma nociceptin level is due to the inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N, endopeptidase 24.15) by the toxic copper levels, as it is known that changing the central Zn atom to Cu results in an approximately 50% inhibition in the activity of these enzymes. The high plasma nociceptin level in Wilson's disease patients may induce significant impairment in nociceptinerg neurotransmission.",Copper/to [Toxicity];Female;*Hepatolenticular Degeneration/bl [Blood];Humans;Liver Function Tests;Male;*Opioid Peptides/bl [Blood];0 (Opioid Peptides);789U1901C5 (Copper);7AYI9N34FF (nociceptin),"Hantos, M. B.;Tekes, K.;Szalay, F.",2002,,,0,0,
472,"Transport and detoxification systems for transition metals, heavy metals and metalloids in eukaryotic and prokaryotic microbes","Transition metals, heavy metals and metalloids are usually toxic in excess, but a number of transition metals are essential trace elements. In all cells there are mechanisms for metal ion homeostasis that frequently involve a balance between uptake and efflux systems. This review will briefly describe ATP-coupled resistance pumps. ZntA and CadA are bacterial P-type ATPases that confers resistance to Zn(II), Cd(II) and Pb(II). Homologous copper pumps include the Menkes and Wilson disease proteins and CopA, an Escherichia coli pump that confers resistance to Cu(I). For resistance to arsenicals and antimonials there are several different families of transporters. In E. coli the ArsAB ATPase is a novel system that confers resistance to As(III) and Sb(III). Eukaryotic arsenic resistance transporters include Acr3p and Ycf1p of Saccharomyces cerevisiae. These systems provide resistance to arsenite [As(III)]. Arsenate [As(V)] detoxification involves reduction of As(V) to As(III), a process catalyzed by arsenate reductase enzymes. There are three families of arsenate reductases, two found in bacterial systems and a third identified in S. cerevisiae. [References: 43]","Biological Transport/ph [Physiology];*Escherichia coli/me [Metabolism];Eukaryotic Cells/me [Metabolism];*Inactivation, Metabolic/ph [Physiology];*Metals, Heavy/me [Metabolism];*Metals, Heavy/to [Toxicity];Prokaryotic Cells/me [Metabolism];*Saccharomyces cerevisiae/me [Metabolism];Trace Elements/me [Metabolism];Trace Elements/to [Toxicity];0 (Metals, Heavy);0 (Trace Elements)","Rosen, B. P.",2002,Nov,,0,0,
473,Molecular mechanism of copper transport in Wilson disease,"Wilson disease is an autosomal recessive disorder of copper metabolism. The Wilson disease protein is a putative copper-transporting P-type ATPase, ATP7B, whose malfunction results in the toxic accumulation of copper in the liver and brain, causing the hepatic and/or neurological symptoms accompanying this disease. The cytosolic N-terminal domain (approximately 70 kDa) of this ATPase comprises six heavy metal-associated domains, each of which contains the conserved metal-binding motif GMTCXXC. The N-terminal domain (Wilson disease copper-binding domain [WCBD]) has been expressed, purified, and characterized using various techniques. The WCBD binds six atoms of copper in the +1 oxidation state competitively, and with a greater affinity than all other metals. The copper atom is coordinated by two cysteines in a distorted linear geometry. Copper binds the WCBD in a cooperative manner and induces secondary and tertiary conformation changes. Zinc binding to the WCBD has also been characterized by circular dichroism spectroscopy and shown to produce conformational changes that are completely different from those induced by copper. The phosphorylation/nucleotide-binding domain of ATP7B has also been expressed and characterized and shown to be capable of binding ATP but lacking ATPase activity. A peptide corresponding to the sixth transmembrane domain of ATP7B has been constructed and shown to undergo secondary conformational changes upon binding a single atom of copper. Finally, a chimeric protein consisting of the WCBD and truncated ZntA, a zinc-transporting ATPase lacking the N-terminal domain, has been constructed and analyzed for metal ion selectivity. These results suggest that the core determines the metal ion specificity of P-type ATPases, and the N-terminal metal-binding domain may play a regulatory role. [References: 54]",*Adenosine Triphosphatases/pd [Pharmacology];Binding Sites;*Cation Transport Proteins/pd [Pharmacology];Copper/ch [Chemistry];*Copper/pk [Pharmacokinetics];Gene Expression Regulation;*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Ions;Phosphorylation;Protein Conformation;0 (Cation Transport Proteins);0 (Ions);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-1 (Zn(II)-translocating P-type ATPase);EC 3-6-3-4 (Wilson disease protein),"Fatemi, N.;Sarkar, B.",2002,Oct,,0,0,
474,Wilson's disease,"Wilson's disease (WD), an inborn error of copper (Cu) metabolism, is now one of the leading liver diseases in children in India. The clinical presentation can be extremely varied viz.,--all forms of acute and chronic liver disease, minimal to severe neurological disease, psychiatric problems, bony deformities, hemolytic anemia and endocrine manifestations. A high index of suspicion is necessary along with a judicious battery of investigations for diagnosis. Hepatic copper estimation is the most reliable test but is not easily available in India. Liver biopsy may not be possible because of bleeding problems and histological features are often not diagnostic of WD. In the absence of hepatic Cu, a low ceruloplasmin, high 24 hour urinary copper and presence of KF rings aid in making the diagnosis. The mainstay of initial therapy is Cu-chelators like D-Penicillamine, and Trientine for reduction in body copper to sub-toxic levels. Subsequent maintenance therapy is necessarily lifelong with D-Penicillamine, Trientine or Zinc. Children on therapy must be monitored regularly for response, side-effects, compliance and rehabilitation. Response to therapy may be unpredictable, but acute and early presentations like fulminant hepatic failures have a poor outcome. All siblings must be screened for WD as early diagnosis and treatment result in a good outcome. The identification of the WD gene on chromosome 13 has led to the possible use of molecular genetics (haplotype and mutational analyses) in the diagnosis of WD. Parent groups/associations must take active part in holistic management of WD. [References: 35]","Adolescent;Biopsy, Needle;Blood Chemical Analysis;Child;Child, Preschool;Combined Modality Therapy;Diet;Female;*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/th [Therapy];Humans;India;Liver Transplantation;Male;Monitoring, Physiologic;Penicillamine/ad [Administration & Dosage];Prognosis;Severity of Illness Index;Treatment Outcome;Trientine/ad [Administration & Dosage];GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Pandit, A.;Bavdekar, A.;Bhave, S.",2002,Sep,,0,0,
475,Elastosis perforans serpiginosa secondary to D-penicillamine treatment in a Wilson's disease patient,,Adolescent;*Antirheumatic Agents/ae [Adverse Effects];Antirheumatic Agents/tu [Therapeutic Use];Arm;*Connective Tissue Diseases/ci [Chemically Induced];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Neck;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];0 (Antirheumatic Agents);GNN1DV99GX (Penicillamine),"Deguti, M. M.;Mucenic, M.;Cancado, E. L.;Tietge, U. J.",2002,Aug,https://dx.doi.org/10.1111/j.1572-0241.2002.05948.x,0,0,
476,Elevated plasma nociceptin level in patients with Wilson disease,"Plasma level of nociceptin, the endogenous agonist of orphanin FQ/ORL1 receptor was found to be significantly elevated in Wilson disease patients (13.98+/-2.44pg/ml, p<0.001, n=20) compared to age-matched healthy controls (9.18+/-1.63pg/ml, n=25). Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutation of the gene ATP7B leading to toxic copper accumulation in the liver and other organs such as brain, kidney and cornea. Measurements were performed by 125I-radioimmunoassay. Neither sex differences nor correlation between plasma nociceptin levels and liver function test results were found. It is suggested that elevated plasma nociceptin level found in Wilson disease patients is due to inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N (APN) and endopeptidase 24.15) by the toxic copper deposits in liver and/or brain.","Adult;Age of Onset;Antigens, CD13/bl [Blood];Chronic Disease;Copper/bl [Blood];Female;*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Metalloendopeptidases/bl [Blood];Middle Aged;*Opioid Peptides/bl [Blood];Opioid Peptides/ge [Genetics];Radioimmunoassay;Sex Characteristics;0 (Opioid Peptides);789U1901C5 (Copper);7AYI9N34FF (nociceptin);EC 3-4-11-2 (Antigens, CD13);EC 3-4-24 (Metalloendopeptidases);EC 3-4-24-15 (thimet oligopeptidase)","Hantos, M. B.;Szalay, F.;Lakatos, P. L.;Hegedus, D.;Firneisz, G.;Reiczigel, J.;Torok, T.;Tekes, K.",2002,Jul,,0,0,
477,Zinc inhibits the nuclear translocation of the tumor suppressor protein p53 and protects cultured human neurons from copper-induced neurotoxicity,"High concentrations of the trace metal zinc (Zn) have previously been shown to provide transient protection of cells from apoptotic death. The molecular mechanisms responsible for this protection are not known. Thus, this work explored the ability of Zn to protect human neurons in culture (NT2-N) from Cu-mediated death and tested the hypotheses that the tumor-suppressor protein p53 plays a role in Cu-induced neuronal death and is part of the mechanism of Zn protection. Copper toxicity (100 microM) resulted in significant apoptotic neuronal death by 12 h. Addition of 100 microM Zn to Cu-treated cells increased neuronal death. However, the addition of 700 microM Zn to Cu-treated cells resulted in neuronal viability that was not different from untreated controls through 24 h. p53 mRNA abundance, while increased by the addition of Cu and 100 microM Zn, was decreased to 50% of control with the addition of 500 microM Zn in Cu-treated cells, and to 10% of control with 700 microM Zn. Consistent with its role as a transcription factor, both Western analysis and immunocytochemistry showed significant increases in nuclear p53 protein levels in Cu toxicity. The role of p53 in Cu-mediated apoptosis was further confirmed by elimination of apoptosis in Cu-treated cells that had been transfected with a dominant-negative p53 construct to prevent p53 expression. Furthermore, the addition of 500-700 microM Zn prevented the movement of p53 into the nucleus suggesting that Zn not only protects neurons from Cu toxicity by regulating p53 mRNA abundance but also by preventing the translocation of p53 to the nucleus.","*Active Transport, Cell Nucleus/de [Drug Effects];Active Transport, Cell Nucleus/ph [Physiology];Annexin A5/me [Metabolism];Apoptosis/de [Drug Effects];Apoptosis/ph [Physiology];Cell Nucleus/de [Drug Effects];Cell Nucleus/pa [Pathology];Cell Survival/de [Drug Effects];Cell Survival/ph [Physiology];Cells, Cultured;*Central Nervous System/de [Drug Effects];Central Nervous System/me [Metabolism];Central Nervous System/pp [Physiopathology];*Copper/ai [Antagonists & Inhibitors];Copper/to [Toxicity];Dose-Response Relationship, Drug;Drug Interactions/ph [Physiology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pp [Physiopathology];Humans;*Neurons/de [Drug Effects];Neurons/me [Metabolism];*Tumor Suppressor Protein p53/de [Drug Effects];Tumor Suppressor Protein p53/me [Metabolism];Up-Regulation/de [Drug Effects];Up-Regulation/ph [Physiology];*Zinc/pd [Pharmacology];0 (Annexin A5);0 (Tumor Suppressor Protein p53);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","VanLandingham, J. W.;Fitch, C. A.;Levenson, C. W.",2002,,https://dx.doi.org/10.1385/NMM:1:3:171,0,0,
478,Liquid chromatographic determination of triethylenetetramine in human and rabbit sera based on intramolecular excimer-forming fluorescence derivatization,"A highly selective and simple fluorimetric liquid chromatographic method for the determination of triethylenetetramine (TETA), a therapeutic drug for Wilson's disease, in human and rabbit sera is described. This method is based on intramolecular excimer-forming fluorescence derivatization, which allows spectrofluorometric discrimination of polyamino compounds from monoamino species, followed by liquid chromatography. TETA and 1,6-hexanediamine (internal standard) were converted to the corresponding excimer-forming derivatives with a pyrene reagent, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester. The derivatives were separated within 20 min on a reversed-phase column using isocratic elution and detected spectofluorometrically at 480 nm with excitation at 345 nm. This method was successfully applied to the monitoring of TETA in human and rabbit sera with a simple pretreatment. The detection limit for TETA in serum was 18 ng/ml (0.13 nmol/ml) corresponding to 0.2 pmol on column at a signal-to-noise ratio of 3.","Adult;Animals;*Chromatography, Liquid/mt [Methods];*Fluorescent Dyes/ch [Chemistry];Humans;Male;Rabbits;Reference Standards;Reproducibility of Results;Sensitivity and Specificity;Spectrometry, Fluorescence;*Trientine/bl [Blood];0 (Fluorescent Dyes);SJ76Y07H5F (Trientine)","Nakano, Y.;Nohta, H.;Yoshida, H.;Saita, T.;Fujito, H.;Mori, M.;Yamaguchi, M.",2002,Jul 15,,0,0,
479,Diagnosis and treatment of Wilson's disease,"Wilson's disease (WD) is an autosomal recessive disease that causes increased copper deposition in the liver and basal ganglia with resultant hepatic and neurologic sequelae. In the past few years, dramatic new discoveries have changed our understanding of the pathophysiology of WD. Although there are potentially life-saving therapies for WD, there is much controversy surrounding the optimal treatments of patients in the various stages of the disease. Specifically, the relative roles of penicillamine, trientene, and tetrathiomolybdate in the initial treatment of the symptomatic patient with WD remain to be defined. Zinc monotherapy for maintenance treatment and in the treatment of asymptomatic patients with WD is still controversial. It is also unclear whether neurologic status alone is an indication for liver transplantation in WD. This paper reviews the pathogenesis, genetics, clinical presentation, and diagnosis, with a special emphasis on the treatment controversies that arise in the care of the WD patient. [References: 49]",*Chelating Agents/tu [Therapeutic Use];Copper/ae [Adverse Effects];*Copper/me [Metabolism];Dimercaprol/tu [Therapeutic Use];Enzyme Inhibitors/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation;Male;Molybdenum/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);0 (Enzyme Inhibitors);0CPP32S55X (Dimercaprol);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Subramanian, I.;Vanek, Z. F.;Bronstein, J. M.",2002,Jul,,0,0,
480,Kayser-Fleischer ring as the presenting sign of Wilson disease,"PURPOSE: To describe a case in which the recognition by the ophthalmologist of Kayser-Fleischer rings played a crucial role in the diagnosis of Wilson disease (hepatolenticular degeneration). DESIGN: Interventional case report. METHODS: An 18-year-old woman was found to have bilateral peripheral golden brown pigment deposits at the level of the Descemet membrane consistent with Kayser-Fleischer rings. She initially denied systemic symptoms. RESULTS: The serum cerumoplasmin level of the patient was normal. Liver function tests were also normal. Further evaluations with 24-hour urine copper assay and liver biopsy were positive for Wilson disease. She underwent anticopper therapy and, 6 months later, reported improved concentration and balance. No appreciable change occurred in the Kayser-Fleischer rings. CONCLUSION: Wilson disease occurs when a defective copper-transporting enzyme in the liver results in toxic copper accumulation in multiple organs. Because of the insidious nature of the disease, patients may not seek medical attention until severe irreversible damage has occurred. By diagnosis of Kayser-Fleischer rings, ophthalmologists may play a critical role in the early recognition and proper evaluation of such patients.","Adolescent;Biopsy;Ceruloplasmin/me [Metabolism];Copper/ur [Urine];Corneal Diseases/bl [Blood];*Corneal Diseases/di [Diagnosis];Corneal Diseases/dt [Drug Therapy];Descemet Membrane/de [Drug Effects];*Descemet Membrane/pa [Pathology];Drug Therapy, Combination;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Function Tests;Molybdenum/tu [Therapeutic Use];Zinc Acetate/tu [Therapeutic Use];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-16-3-1 (Ceruloplasmin);FM5526K07A (Zinc Acetate)","Liu, M.;Cohen, E. J.;Brewer, G. J.;Laibson, P. R.",2002,Jun,,0,0,
481,Proton MR spectroscopy of basal ganglia in Wilson's disease: case report and review of literature,"Volume localized proton Magnetic Resonance Spectroscopy was carried out in both the left and right basal ganglia of three patients with clinically proven Wilson's Disease. While the untreated patient died 15 days after the spectroscopy study, the other 2 patients have been under treatment and have shown clinical improvement. The spectral features of the untreated patient were very different from those of the other two patients who were under treatment and responding. Asymmetrical changes in NAA and Cho were also observed for this patient.","Adolescent;*Basal Ganglia/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Child;Choline/me [Metabolism];Creatine/me [Metabolism];Drug Therapy, Combination;Fatal Outcome;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Magnetic Resonance Spectroscopy/mt [Methods];*Magnetic Resonance Spectroscopy;Male;Penicillamine/tu [Therapeutic Use];Pyridoxine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine);MU72812GK0 (Creatine);N91BDP6H0X (Choline)","Jayasundar, R.;Sahani, A. K.;Gaikwad, S.;Singh, S.;Behari, M.",2002,Jan,,0,0,
482,Diagnosis and treatment of Wilson's disease,"Wilson's disease (WD) has moved on from being a recognized syndrome that was uniformly fatal to a curative disease for which the genetic basis has been discovered. Most pediatric patients present with hepatic manifestations, but some may have neurologic or psychiatric features. Clinical and biochemical screening, including liver biopsy for hepatic copper analysis, remain the standard for diagnosis, but haplotype analysis for siblings is now available and should be considered for family screening when possible. Lifelong medical therapy remains the mainstay of treatment, but treatment preferences are changing from penicillamine to alternative agents such as trientine and zinc. OLT remains lifesaving for those with fulminant WD and those in whom initial medical therapy fails. The future will probably see the application of rapid and accurate molecular diagnostic testing for this disorder and new therapeutic modalities such as hepatocyte transplantation, gene replacement therapy, and gene modification. [References: 14]","Chelating Agents/ad [Administration & Dosage];Child;Child, Preschool;Chronic Disease;Combined Modality Therapy;Female;Genetic Therapy/mt [Methods];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation/mt [Methods];Long-Term Care;Male;Prognosis;Risk Assessment;Survival Rate;0 (Chelating Agents)","Schilsky, M. L.",2002,Feb,,0,0,
483,Radiotherapy and antiangiogenic TM in lung cancer,"Tetrathiomolybdate (TM) is a potent nontoxic orally delivered copper complexing agent under development for the last several years for the treatment of Wilson's disease. It has been shown to block angiogenesis in primary and metastatic tumors. Therefore, the combination of cytotoxic radiotherapy (RT) and antiangiogenic TM could target both the existing tumor and the tumor microvasculature in a comprehensive strategy. Using a Lewis lung high metastatic (LLHM) carcinoma mouse tumor model, we demonstrate that the combination of TM and RT is more effective than either used as monotherapy. We also show that their therapeutic effects are additive, with no additional toxicity. We show that TM has no significant cytotoxicity in vitro against LLHM tumor cells, further supporting the antiangiogenic mechanism for its action.","*Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;Carcinoma, Lewis Lung/bs [Blood Supply];Carcinoma, Lewis Lung/pa [Pathology];*Carcinoma, Lewis Lung/th [Therapy];Cell Division/de [Drug Effects];Combined Modality Therapy;Disease Models, Animal;Dose-Response Relationship, Drug;Female;Humans;Lung Neoplasms/bs [Blood Supply];Lung Neoplasms/pa [Pathology];*Lung Neoplasms/th [Therapy];Male;Mice;Mice, Inbred C57BL;Middle Aged;*Molybdenum/tu [Therapeutic Use];*Neovascularization, Pathologic/dt [Drug Therapy];Radiotherapy;Tetrazolium Salts;Thiazoles;Tumor Cells, Cultured/de [Drug Effects];Tumor Cells, Cultured/me [Metabolism];0 (Angiogenesis Inhibitors);0 (Tetrazolium Salts);0 (Thiazoles);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EUY85H477I (thiazolyl blue)","Khan, M. K.;Miller, M. W.;Taylor, J.;Gill, N. K.;Dick, R. D.;Van Golen, K.;Brewer, G. J.;Merajver, S. D.",2002,Mar-Apr,https://dx.doi.org/10.1038/sj/neo/7900218,0,0,
484,"""Mowat-Wilson"" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene","Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with ""syndromic Hirschsprung disease"" with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617-623] is specific for ZFHX1B mutations. In order to address these open questions we analyzed the ZFHX1B gene in five patients, three of whom had ""syndromic Hirschsprung disease"" two with and one without the facial phenotype described by Mowat et al. [1998], and two of whom had the distinct facial gestalt without Hirschsprung disease. Analyses of microsatellite markers and newly identified SNPs, and/or FISH with BACs from the ZFHX1B region excluded large deletions in all five patients. Direct sequencing demonstrated truncating ZFHX1B mutations in all four patients with the characteristic facial phenotype, but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. We demonstrate that there is a specific clinical entity with a recognizable facial gestalt, mental retardation and variable MCAs which we propose be called the ""Mowat-Wilson syndrome.""","*Abnormalities, Multiple/ge [Genetics];Abnormalities, Multiple/pa [Pathology];Base Sequence;Child;Child, Preschool;DNA/ch [Chemistry];DNA/ge [Genetics];DNA Mutational Analysis;*Genes, Homeobox;*Hirschsprung Disease/pa [Pathology];Humans;Infant;*Intellectual Disability/ge [Genetics];Intellectual Disability/pa [Pathology];Male;Mutation;Syndrome;*Zinc Fingers/ge [Genetics];9007-49-2 (dna)","Zweier, C.;Albrecht, B.;Mitulla, B.;Behrens, R.;Beese, M.;Gillessen-Kaesbach, G.;Rott, H. D.;Rauch, A.",2002,Mar 15,,0,0,
485,Zinc binding to the NH2-terminal domain of the Wilson disease copper-transporting ATPase: implications for in vivo metal ion-mediated regulation of ATPase activity,"Mutations in the Wilson disease copper transporting, P-type ATPase lead to the accumulation of toxic levels of copper in the liver, brain, and kidney causing extensive tissue damage and eventual death. The NH(2)-terminal domain ( approximately 70 kDa), which contains six copies of the heavy metal-associated repeat GMT/HCXXC, is also able to bind zinc. We have used circular dichroism (CD) and x-ray absorption spectroscopy (XAS) to characterize zinc binding to the NH(2)-terminal metal-binding domain. These studies have revealed that zinc is able to bind to this domain with a stoichiometry of 6:1, and upon binding, induces conformational changes in the NH(2)-terminal domain. These conformational changes are completely different from those previously observed for copper binding to the domain and lead to an overall loss of secondary structure in the domain. The XAS spectra indicate that zinc is ligated primarily by nitrogen atoms and therefore has low affinity for the heavy metal-associated repeats where copper has been shown to bind. The differences between zinc and copper binding may serve as the basis for the metal-ion mediated regulation of the ATPase in vivo.","*Adenosine Triphosphatases/ch [Chemistry];*Adenosine Triphosphatases/me [Metabolism];*Cation Transport Proteins/ch [Chemistry];*Cation Transport Proteins/me [Metabolism];Circular Dichroism;DNA, Complementary/me [Metabolism];Glutathione Transferase/me [Metabolism];Humans;Ions;Nitrogen/ch [Chemistry];Protein Binding;Protein Conformation;Protein Structure, Secondary;Protein Structure, Tertiary;Recombinant Fusion Proteins/me [Metabolism];Spectroscopy, Fourier Transform Infrared;*Zinc/me [Metabolism];0 (Cation Transport Proteins);0 (DNA, Complementary);0 (Ions);0 (Recombinant Fusion Proteins);EC 2-5-1-18 (Glutathione Transferase);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc);N762921K75 (Nitrogen)","DiDonato, M.;Zhang, J.;Que, L., Jr.;Sarkar, B.",2002,Apr 19,https://dx.doi.org/10.1074/jbc.M111649200,0,0,
486,Dense Kayser-Fleischer ring in asymptomatic Wilson's disease (hepatolenticular degeneration),,Chelating Agents/tu [Therapeutic Use];Child;*Copper/me [Metabolism];Corneal Diseases/dt [Drug Therapy];*Corneal Diseases/et [Etiology];Corneal Diseases/me [Metabolism];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Male;Pigmentation Disorders/dt [Drug Therapy];*Pigmentation Disorders/et [Etiology];Pigmentation Disorders/me [Metabolism];Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);SJ76Y07H5F (Trientine),"Sullivan, C. A.;Chopdar, A.;Shun-Shin, G. A.",2002,Jan,,0,0,
487,Acute haemolytic syndrome and liver failure as the first manifestations of Wilson's disease,"Acute liver failure and haemolytic syndrome appeared quite suddenly as the first manifestations of Wilson disease (WD) in five of our patients previously regarded as healthy persons (although an interview showed that 2-4 weeks prior to the illness the patients complained of several non-specific symptoms, such as abdominal pain, headaches, fever, weakness or behavioural changes). All the patients were young women (17-23 years), none of them had any history of liver disease. They were admitted with icterus, nausea, vomiting and symptoms of increasing haemolysis. The diagnosis of WD was given as disturbed copper metabolism. After a short period of observation ascites and anasarca occurred, haemorrhagic diathesis and other symptoms of liver failure increased. Levels of clotting factors decreased rapidly. Despite treatment with D-penicillamine, plasmapheresis, and symptomatic drugs, three of the women died in irreversible liver coma, due to the unavailability of liver transplantation. The fourth woman was carried to the Transplantation Centre, due to aggravation of the symptoms of liver failure, where liver transplantation was performed. Histopathologically micronodular cirrhosis was shown in all these cases. The fifth patient survived having undergone the above treatment without liver transplantation. The main differences between the patient who survived and those who died or underwent transplantation were relatively higher activity of alkaline phosphatase (26 U/l vs. 10-20 U/l), slightly higher levels of clotting factors and prothrombin time, which never fall below 68% of the control (versus 14-44% in other patients). Only in the surviving patient was the Kayser-Fleischer ring present. In four of our patients we found family members who were carriers of WD.",Adolescent;Adult;Alkaline Phosphatase/bl [Blood];Female;*Hematologic Diseases/pa [Pathology];*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/ge [Genetics];Humans;*Liver Failure/pa [Pathology];Mutation;Necrosis;EC 3-1-3-1 (Alkaline Phosphatase),"Dabrowska, E.;Jablonska-Kaszewska, I.;Ozieblowski, A.;Falkiewicz, B.",2001,May,,0,0,
488,Wilson's disease: from the liver to the brain,,Benchmarking;Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/th [Therapy];Humans;Mass Screening;*Nurse's Role;Penicillamine/tu [Therapeutic Use];Time Factors;Trientine/tu [Therapeutic Use];Zinc Acetate/tu [Therapeutic Use];Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Taylor, R.;Dhawan, A.",2001,Jul 26-Aug 1,,0,0,
489,Disturbed copper transport in humans. Part 2: mutations of the ATP7B gene lead to Wilson disease (WD),"Mutations in the Wilson disease gene ATP7B, a P-type ATPase, are responsible for copper accumulation in the liver and other organs leading to Wilson disease (WD, OMIM 277900). Clinical manifestations of Wilson disease (WD) include chronic liver disease, acute hepatic failure or neuropsychiatric diseases. Since potent medical treatments are available to prevent disabling residual symptoms, early diagnosis is crucial. To demonstrate the clinical course and genetic findings, a male patient with a novel mutation in the ATP7B gene, a 10 base pair insertion in exon 6 (1927ins 10), and a second missense mutation in exon 13 (P992L) is reported. The patient presented with signs of chronic liver disease at the age of 10 years. Clinical findings included hepatomegaly, elevated liver enzymes and coagulopathy. A combination treatment with the copper chelating agent D-penicillamine and zinc acetate was started leading to normalization of liver function and no appearance of neurological signs or Kayser-Fleischer ring after 7 years follow-up. Truncating mutations of the ATP7B gene (insertions, deletions, nonsense mutations) leading to gross loss of C-terminal parts of the protein, thereby probably completely destroying the protein function, may correlate with a hepatic phenotype and early onset as seen in the patient presented.","*Adenosine Triphosphatases/ge [Genetics];Adolescent;Base Sequence;*Cation Transport Proteins/ge [Genetics];*Copper/me [Metabolism];Copper/ur [Urine];DNA/ge [Genetics];DNA Mutational Analysis;Exons;Genotype;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Mutation;Mutation, Missense;Penicillamine/tu [Therapeutic Use];Phenotype;Zinc Acetate/tu [Therapeutic Use];0 (Cation Transport Proteins);789U1901C5 (Copper);9007-49-2 (dna);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);FM5526K07A (Zinc Acetate);GNN1DV99GX (Penicillamine)","Seidel, J.;Caca, K.;Schwab, S. G.;Berr, F.;Wildenauer, D. B.;Mentzel, H. J.;Horn, N.;Kauf, E.",2001,,,0,0,
490,Wilson's disease in Eastern India,"INTRODUCTION: Wilson's disease is an inherited autosomal recessive (AR) disorder of copper metabolism transmitted by a mutant gene on chromosome 13q14-21 and results in abnormal accumulation of copper giving rise to protean manifestations. AIM: The aim is to study the clinical features, biochemical and radiological abnormalities of this disorder in Eastern India and the effect of treatment. RESULTS: Forty nine (n = 49) cases were studied over a period of 10 years. Majority of patients were male with mean age of onset being 11.13 years. They commonly presented with dysarthria, dystonia or drooling. The clinical features were dystonia (96%), silly smile (92%), dysarthria (80%), cognitive decline (71%), tremors (47%), bradykinesia (45%), etc. Family history suggested an autosomal recessive pattern. Sibling screening revealed that 4/8 (50%) were presymptomatic. All but one had presence of Keyser Fleischer (KF) ring in their cornea. Serum copper was reduced in 77% while ceruloplasmin was less in 94% of cases. The commonest abnormality seen in CT/MRI were in basal ganglia (74%) followed by white matter changes (59%) and brain stem changes (20.5%). The response to treatment was not as good and there was an initial deterioration in 50% of cases. Only five patients could go back to their school. CONCLUSION: Wilson's disease have protean manifestations. All children with slowly progressive extrapyramidal syndrome should be investigated for it. Screening of all asymptomatic siblings for Wilson's disease must be carried out. Early institution of proper treatment and life long continuation is indicated in all. In the present series, an earlier age of onset of neurological signs and symptoms were seen; there was initial deterioration in 50% of cases and the response to treatment was not as good.",Adolescent;Adult;Age Distribution;Age of Onset;Child;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ep [Epidemiology];Humans;Incidence;India/ep [Epidemiology];Male;Penicillamine/tu [Therapeutic Use];Prognosis;Retrospective Studies;Risk Factors;Severity of Illness Index;Sex Distribution;GNN1DV99GX (Penicillamine),"Sinha, S.;Jha, D. K.;Sinha, K. K.",2001,Sep,,0,0,
491,Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells,"Wilson's disease, a genetic copper-overload condition, is currently treated with zinc because of the ability of zinc to induce metallothionein. We are interested in nonmetal chemicals that may alter intestinal copper metabolism and thus help to alleviate copper toxicity. Previously, we have shown that quercetin, a dietary flavonoid, can chelate copper. This study further examined the interaction of quercetin and copper in intestinal epithelial cells. We found that quercetin enhanced metallothoinein induction by copper and the effect was dose dependent. Quercetin also exerted a cumulative effect after repeated exposure. Repeated low-dose treatment (3-10 microM) of cells with quercetin can lead to the same effect on metallothoinein as one higher concentration treatment (100 microM). This property of quercetin is distinct from its chemical interaction with copper, but both can contribute to a reduction of copper toxicity. Among other flavonoids tested, two other copper chelators, catechin and rutin, did not increase copper induction of metallothionein, whereas genistein, an isoflavone that does not interact with copper chemically, increased copper induction of metallothionein. The effect of quercetin on copper metabolism is unique. Quercetin decreased zinc-stimulated metallothionein expression and had no effect on the cadmium induction of metallothionein. The clinical application of our observation needs to be explored.","Cadmium/pd [Pharmacology];Catechin/me [Metabolism];*Copper/me [Metabolism];Dose-Response Relationship, Drug;*Flavonoids/me [Metabolism];Genistein/pd [Pharmacology];Humans;*Intestines/me [Metabolism];*Metallothionein/me [Metabolism];*Quercetin/pd [Pharmacology];RNA, Messenger/me [Metabolism];Rutin/me [Metabolism];Tumor Cells, Cultured;0 (Flavonoids);0 (RNA, Messenger);00BH33GNGH (Cadmium);5G06TVY3R7 (Rutin);789U1901C5 (Copper);8R1V1STN48 (Catechin);9038-94-2 (Metallothionein);9IKM0I5T1E (Quercetin);DH2M523P0H (Genistein)","Kuo, S. M.;Huang, C. T.;Blum, P.;Chang, C.",2001,Winter,https://dx.doi.org/10.1385/BTER:84:1-3:001,0,0,
492,"Brain copper, iron, magnesium, zinc, calcium, sulfur and phosphorus storage in Wilson's disease","PROJECT: Wilson's disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms. Copper levels in brain in WD have been reported to be 10 to 15 fold normal values, depending on the different brain regions. Being very few data on copper distribution in central nervous system in WD available, it seemed of interest to study the concentration of copper and of other trace elements (Zn, P, Mg, Ca, Fe and S) in the brain of a patient died for WD. PROCEDURE: a 56 year old woman affected by WD was admitted to our hospital with signs of hepatic failure and died few days later. At autopsy, a brain slice extending from the left to the right hemisphere was divided in 28 samples. On each sample Copper, Iron, Magnesium, Phosphorus, Sulphur, Zinc and Calcium were determined by Induced Coupled Plasma Atomic Emission Spectroscopy. RESULTS: the mean concentration of copper, ranging from 88 to 158 microg/g of dry tissue in all the brain specimens was higher than literature reference values, while that of the other tested elements was considerably lower. CONCLUSIONS: 1) In the brain of WD patient examined the status of trace elements was extensively altered. Further studies are necessary to correlate the concentration of trace elements with pathological lesions and with clinical pictures. 2) The elements considered in our study showed an uneven distribution in different brain areas.",*Brain/me [Metabolism];Brain/pa [Pathology];*Calcium/an [Analysis];*Copper/an [Analysis];Female;*Hepatolenticular Degeneration/me [Metabolism];Humans;*Iron/an [Analysis];*Magnesium/an [Analysis];Middle Aged;*Phosphorus/an [Analysis];Phosphorus/me [Metabolism];Spectrophotometry;*Sulfur/an [Analysis];*Zinc/an [Analysis];27YLU75U4W (Phosphorus);70FD1KFU70 (Sulfur);789U1901C5 (Copper);E1UOL152H7 (Iron);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc);SY7Q814VUP (Calcium),"Faa, G.;Lisci, M.;Caria, M. P.;Ambu, R.;Sciot, R.;Nurchi, V. M.;Silvagni, R.;Diaz, A.;Crisponi, G.",2001,,https://dx.doi.org/10.1016/S0946-672X(01)80060-2,0,0,
493,Iron accumulation in the liver of male patients with Wilson's disease,"OBJECTIVES: There is accumulating evidence that ceruloplasmin, a copper protein with ferroxidase activity, plays an important role in iron metabolism. The genetic disorder, aceruloplasminemia, can lead to tissue storage of iron as in hemochromatosis. Because most patients with Wilson's disease, a genetic copper toxicosis, have hypoceruloplasminemia, some could be affected by iron overload. METHODS: Four male patients with Wilson's disease were enrolled in this study of pre- and post-treatment iron metabolism. RESULTS: Pretreatment copper contents of the liver were high in all four male patients studied as diagnostic of Wilson's disease. Genetic analysis supported their clinical diagnosis of Wilson's disease without a background of hemochromatosis. Pretreatment serum ceruloplasmin levels were <20 mg/dl in all four patients. A standard penicillamine treatment for 3-8.5 yr further decreased their serum ceruloplasmin levels. Post-treatment serum ferroxidase activity was low as was the serum ceruloplasmin protein. Copper contents in the liver decreased after treatment in all subjects. In contrast, nonheme iron in the liver increased during treatment. Pretreatment liver specimens were positive for histochemical iron in two patients, and post-treatment specimens were positive in all four patients. In two patients, serum aminotransferase levels rebounded with elevation of serum ferritin concentration during the treatment period. Subsequent iron reduction by phlebotomy ameliorated their biochemical liver damage. CONCLUSION: Iron overload related to hypoceruloplasminemia may be clinically important, particularly in male patients with Wilson's disease.",Adolescent;Adult;*Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;*Iron/me [Metabolism];*Liver/me [Metabolism];Male;*Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);E1UOL152H7 (Iron);GNN1DV99GX (Penicillamine),"Shiono, Y.;Wakusawa, S.;Hayashi, H.;Takikawa, T.;Yano, M.;Okada, T.;Mabuchi, H.;Kono, S.;Miyajima, H.",2001,Nov,https://dx.doi.org/10.1111/j.1572-0241.2001.05269.x,0,0,
494,Tetrathiomolybdate inhibition of the Enterococcus hirae CopB copper ATPase,"Tetrathiomolybdate (TTM) avidly interacts with copper and has recently been employed to reduce excess copper in patients with Wilson disease. We found that TTM inhibits the purified Enterococcus hirae CopB copper ATPase with an IC(50) of 34 nM. Dithiomolybdate and trithiomolybdate, which commonly contaminate TTM, inhibited the copper ATPases with similar potency. Inhibition could be reversed by copper or silver, suggesting inhibition by substrate binding. These findings for the first time allowed an estimate of the high affinity of CopB for copper and silver. TTM is a new tool for the study of copper ATPases.","*Adenosine Triphosphatases/ai [Antagonists & Inhibitors];*Cation Transport Proteins/ai [Antagonists & Inhibitors];Copper/pd [Pharmacology];*Enzyme Inhibitors/pd [Pharmacology];Inhibitory Concentration 50;*Molybdenum/pd [Pharmacology];Quinolines/pd [Pharmacology];Silver/pd [Pharmacology];0 (Cation Transport Proteins);0 (Enzyme Inhibitors);0 (Quinolines);3M4G523W1G (Silver);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);CX56TX9Y1I (bicinchoninic acid);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-1 (CopB ATPase, Enterococcus hirae)","Bissig, K. D.;Voegelin, T. C.;Solioz, M.",2001,Nov 02,,0,0,
495,Personality traits in treated Wilson's disease determined by means of the Karolinska Scales of Personality (KSP),"OBJECTIVE: The aim was to elucidate the personality traits of patients with treated Wilsons disease (WD) in comparison to healthy volunteers. METHOD: Twenty-five WD patients, ten females and 15 males, with a mean age of 35.2 +/- 8.3 years completed the Karolinska Scales of Personality (KSP), a self-report inventory comprising 15 separate scales. The results were compared to a control series comprising 200 men and 200 women drawn from the general population. RESULTS: The patients with treated WD scored significantly lower than the healthy controls on aggressivity-hostility-related scales and the scale measuring Psychic Anxiety. Patients with predominantly hepatic symptoms had the lowest aggressivity-related scores and patients with predominantly neurological symptoms had the lowest Irritability, Guilt and Detachment scores and the highest Impulsiveness and Muscular Tension scores. Both groups scored low on the Somatic Anxiety scale. CONCLUSION: The present results illustrate that patients with treated WD have significant deviations in personality traits, especially in aggressivity-hostility-related scales and Psychic Anxiety, compared to healthy controls when investigated by means of a self-report inventory, the KSP. The deviations were not related to age, age at onset or duration of the disease.",Adult;*Aggression/de [Drug Effects];*Arousal/de [Drug Effects];Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];*Hostility;Humans;Male;Middle Aged;Penicillic Acid/ae [Adverse Effects];*Penicillic Acid/aa [Analogs & Derivatives];*Penicillic Acid/tu [Therapeutic Use];*Personality Inventory;Psychometrics;Reproducibility of Results;Trientine/ae [Adverse Effects];*Trientine/tu [Therapeutic Use];Zinc Acetate/ae [Adverse Effects];*Zinc Acetate/tu [Therapeutic Use];34138-28-8 (penicillamide);FM5526K07A (Zinc Acetate);ONL14K3AFD (Penicillic Acid);SJ76Y07H5F (Trientine),"Portala, K.;Westermark, K.;Ekselius, L.;von Knorring, L.",2001,Sep,,0,0,
496,Zinc acetate for the treatment of Wilson's disease,"Zinc acetate (Galzin, Gate Pharmaceutical Co.) has been developed for the treatment of Wilson's disease, an inherited disease of copper accumulation and copper toxicity in brain and liver. Zinc acetate has been approved by the US FDA for maintenance therapy of adult and paediatric Wilson's disease patients but also has efficacy in the treatment of pregnant patients and presymptomatic patients from the beginning. It also has value as adjunctive therapy for the initial treatment of symptomatic patients. Zinc's mechanism of action involves induction of intestinal cell metallothionein (Mt), which blocks copper absorption from the intestinal track. A negative copper balance is caused by blockade not only of absorption of food copper but the blockade of reabsorption of the considerable amount of endogenously secreted copper in saliva, gastric juice and intestinal secretions. Zinc is completely effective in controlling copper levels and toxicity in Wilson's disease, as are other anticopper agents. Zinc's major advantage over other anticopper agents is its extremely low level of toxicity. The only side effect is some degree of initial gastric irritation in approximately10% of patients, which usually decreases and becomes insignificant over time. As with all long-term therapies, compliance is a problem in some patients and dictates regular monitoring with 24 h urine copper and zinc measurements. As with all anticopper therapies, over a long period of time, overtreatment and induction of copper deficiency can occur. This is to be avoided particularly in children because copper is required for growth. [References: 30]",Animals;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Zinc Acetate/pk [Pharmacokinetics];*Zinc Acetate/tu [Therapeutic Use];FM5526K07A (Zinc Acetate),"Brewer, G. J.",2001,Sep,https://dx.doi.org/10.1517/14656566.2.9.1473,0,0,
497,Using zinc to remove copper from pediatric patients with Wilson's disease,,"Biomarkers/bl [Blood];Child;Child, Preschool;Cholesterol, HDL/bl [Blood];Copper/df [Deficiency];Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Zinc/ad [Administration & Dosage];Zinc/ae [Adverse Effects];0 (Biomarkers);0 (Cholesterol, HDL);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Klevay, L. M.",2001,Sep,,0,0,
498,"Functional analysis of chimeric proteins of the Wilson Cu(I)-ATPase (ATP7B) and ZntA, a Pb(II)/Zn(II)/Cd(II)-ATPase from Escherichia coli","ATP7B, the Wilson disease-associated Cu(I)-transporter, and ZntA from Escherichia coli are soft metal P1-type ATPases with mutually exclusive metal ion substrates. P1-type ATPases have a distinctive amino-terminal domain containing the conserved metal-binding motif GXXCXXC. ZntA has one copy of this motif while ATP7B has six copies. The effect of interchanging the amino-terminal domains of ATP7B and ZntA was investigated. Chimeric proteins were constructed in which either the entire amino-terminal domain of ATP7B or only its sixth metal-binding motif replaced the amino-terminal domain of ZntA. Both chimeras conferred resistance to lead, zinc, and cadmium salts but not to copper salts. The purified chimeras displayed activity with lead, cadmium, zinc, and mercury, which are substrates of ZntA. There was no activity with copper or silver, which are substrates of ATP7B. The chimeras were 2-3-fold less active than ZntA. Thus, the amino-terminal domain of P1-type ATPases cannot alter the metal specificity determined by the transmembrane segment. Also, these results suggest that this domain interacts with the rest of the transporter in a metal ion-specific manner; the amino-terminal domain of ATP7B cannot replace that of ZntA in restoring full catalytic activity.","Adenosine Triphosphatases/ge [Genetics];*Adenosine Triphosphatases/me [Metabolism];Base Sequence;Cation Transport Proteins/ge [Genetics];*Cation Transport Proteins/me [Metabolism];Copper/pd [Pharmacology];DNA Primers;*Escherichia coli/en [Enzymology];*Hepatolenticular Degeneration/en [Enzymology];Lead/pd [Pharmacology];Mutagenesis, Site-Directed;Recombinant Fusion Proteins/ge [Genetics];Recombinant Fusion Proteins/ip [Isolation & Purification];*Recombinant Fusion Proteins/me [Metabolism];Zinc/me [Metabolism];Zinc/pd [Pharmacology];0 (Cation Transport Proteins);0 (DNA Primers);0 (Recombinant Fusion Proteins);2P299V784P (Lead);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-1 (Zn(II)-translocating P-type ATPase);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc)","Hou, Z. J.;Narindrasorasak, S.;Bhushan, B.;Sarkar, B.;Mitra, B.",2001,Nov 02,https://dx.doi.org/10.1074/jbc.M107455200,0,0,
499,Low-dose zinc administration as an effective Wilson's disease treatment,"A case of a 11-yr-long Wilson's disease treatment in a 16-yr-old boy with neurologic presentation was analyzed and monitored. In the face of severe symptoms of chelator intolerance, a comparatively low dose of 100 mg of zinc has been administered for the entire 11-yr-long treatment. Considerable improvement of clinical status was achieved, with accompanying regression of central nervous system lesion. The parameters of copper metabolism were normalized with effective urine elimination. The low-dose oral zinc intake proved to be therapeutically effective, eliminating further copper tissue toxicity.",Adolescent;Adult;Copper/bl [Blood];Copper/me [Metabolism];Copper/to [Toxicity];Copper/ur [Urine];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/ur [Urine];Humans;Male;Time Factors;*Zinc/ad [Administration & Dosage];Zinc/bl [Blood];*Zinc/tu [Therapeutic Use];Zinc/ur [Urine];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Najda, J.;Stella-Holowiecka, B.;Machalski, M.",2001,Jun,https://dx.doi.org/10.1385/BTER:80:3:281,0,0,
500,Ultrastructural identification of iron and copper accumulation in the liver of a male patient with Wilson disease,"There is accumulating evidence that ceruloplasmin, a copper-containing protein with ferroxidase activity, plays an important role in iron metabolism. Reduction of ferroxidase activity secondary to ceruloplasmin deficiency may induce iron accumulation in various organs as the result of impaired iron transport. A 37-year-old man presented with intention tremor of the right hand. Liver function tests were almost normal, but parameters of trace elements were abnormal: hypocupremia, hypoceruloplaminemia, and hyperferritinemia. Imaging of the abdomen showed a cirrhotic liver with increased density. A diagnosis of the neurological form of Wilson disease was confirmed by copper deposits in the liver obtained by a blind biopsy, and the patient was diagnosed as compound heterozygous for ATP7B mutations. He was treated with 2500 mg/day trientine hydrochloride per os. The second examination was performed after 20 months of treatment. The treatment further reduced serum ceruloplasmin level from 8.9 to less than 4.0 mg/dl. Serum ferroxidase activity was as low as 70 U/l during treatment. Posttreatment liver histology became negative for copper but remained positive for iron. Copper X-rays from hepatocyte lysosomes were no longer detected, but the iron X-ray was still very high post treatment. Thus, microanalysis confirmed compound overload of copper and iron in this male patient with Wilson disease.","Adult;Biopsy;Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Copper/an [Analysis];*Copper/me [Metabolism];Electron Probe Microanalysis;Ferritins/an [Analysis];Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Histocytochemistry;Humans;Iron/an [Analysis];*Iron/me [Metabolism];*Liver/me [Metabolism];Liver/ul [Ultrastructure];Male;Microscopy, Electron;Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);9007-73-2 (Ferritins);E1UOL152H7 (Iron);EC 1-16-3-1 (Ceruloplasmin);SJ76Y07H5F (Trientine)","Shiono, Y.;Hayashi, H.;Wakusawa, S.;Yano, M.",2001,Mar,https://dx.doi.org/10.1007/s0079510340054,0,0,
501,Haemolytic onset of Wilson disease in a patient with homozygous truncation of ATP7B at Arg1319,"We describe a 19-year-old woman with haemolytic anaemia and thrombocytopenia as the initial manifestation of Wilson disease (WD). There are two reasons for reporting such an improbable case. First, it emphasizes the importance of recognizing atypical clinical presentations of potentially lethal recessive traits for which therapy is available. Second, it shows that, even in a monogenic disorder like WD, the phenotype cannot be extrapolated from the mutated genotype in a simple fashion; this patient had a relatively late-onset form of WD despite homozygosity for a genetic lesion leading to an apparent complete loss of function of the WD copper transporter.","*Adenosine Triphosphatases/ge [Genetics];Adult;Anemia, Hemolytic/dt [Drug Therapy];*Anemia, Hemolytic/et [Etiology];*Carrier Proteins/ge [Genetics];*Cation Transport Proteins;Chelating Agents/tu [Therapeutic Use];Chelation Therapy;Copper;Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Homozygote;Humans;Male;Mutation;Sequence Analysis, DNA;Thrombocytopenia/dt [Drug Therapy];*Thrombocytopenia/et [Etiology];Trientine/tu [Therapeutic Use];0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);SJ76Y07H5F (Trientine)","Prella, M.;Baccala, R.;Horisberger, J. D.;Belin, D.;Di Raimondo, F.;Invernizzi, R.;Garozzo, R.;Schapira, M.",2001,Jul,,0,0,
502,"Generalised oedema, lethargy, personality disturbance, and recurring nightmares in a young girl",,Adolescent;Biopsy;Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Edema/di [Diagnosis];*Edema/et [Etiology];Edema/th [Therapy];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation;Penicillamine/tu [Therapeutic Use];Personality Disorders/di [Diagnosis];*Personality Disorders/et [Etiology];Personality Disorders/th [Therapy];Sleep Wake Disorders/di [Diagnosis];*Sleep Wake Disorders/et [Etiology];Sleep Wake Disorders/th [Therapy];0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Hawkes, N. D.;Mutimer, D.;Thomas, G. A.",2001,Aug,,0,0,
503,Copper control as an antiangiogenic anticancer therapy: lessons from treating Wilson's disease,"The search for new anticopper drugs for Wilson's disease is culminating in two excellent new drugs: zinc for maintenance therapy and tetrathiomolybdate (TM) for initial therapy. Both are effective and nontoxic. TM is a very potent, fast-acting new anticopper drug and its properties may be useful well beyond Wilson's disease. Angiogenesis (new blood vessel growth) is required for tumor growth, and a sufficient level of copper appears to be required for angiogenesis. We hypothesize that there is a ""window"" to which the copper level can be reduced that inhibits angiogenesis in tumors, but does not interfere with vital cellular functions of copper. Using TM therapy, this approach has worked to slow or stabilize tumor growth in several animal tumor models, and preliminary results are also very encouraging in human patients with a variety of advanced and metastatic malignancies. A hypothesis is advanced that copper availability has played a fundamental role in growth regulation throughout evolution and that is the reason that so many angiogenic promoters appear to be dependent upon copper levels. [References: 80]",*Angiogenesis Inhibitors/tu [Therapeutic Use];Animals;*Antineoplastic Agents/tu [Therapeutic Use];Copper/ai [Antagonists & Inhibitors];*Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/tu [Therapeutic Use];Neoplasms/dt [Drug Therapy];Zinc/tu [Therapeutic Use];0 (Angiogenesis Inhibitors);0 (Antineoplastic Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc),"Brewer, G. J.",2001,Jul,,0,0,
504,Is Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD?,"Wilson's disease (WD) patients often present with Parkinson's disease (PD). Furthermore, most patients with PD have reduced ceruloplasmin, a characteristic of Wilson's disease. WD is an autosomal recessive disease (requires two faulty copies of a gene to produce a homozygote individual) that afflicts 1 in 1000 people. However, the number of people with one faulty copy (heterozygotes) is much larger, probably about 2% of the population. I hypothesize that the large number of heterozygotes for WD are at greatly increased risk for idiopathic PD, because these people accumulate free copper in the basal ganglia at a slower rate than homozygotes, which accounts for the fact that PD usually develops after 40 years of age. In WD, a ceruloplasmin deficiency results in accumulation of free Cu in the liver, brain, kidneys, etc. The excess Cu results in impaired Zn absorption, which would account for the low levels of Zn in the brains of PD patients. Moreover, the high levels of Fe found in the substantia nigra of PD patients may perhaps be explained by free Cu binding to iron binding protein-1 (IBP-1), causing it to malfunction and preventing it from detaching itself from the transferrin receptor (TfR) inhibition gene, resulting in expression of TfR even when the cell has plenty of Fe. The gradual accumulation of Fe and Cu would explain the damage inflicted on the substantia nigra by free radicals catalyzed by these two metals and which is exacerbated by the low levels of CuZnSOD, due to the Zn deficiency mentioned above. Moreover, if this hypothesis is correct, then PD could be used to help discover the gene (or genes) responsible for WD and vice versa. Furthermore, idiopathic PD could be prevented by identifying the heterozygote individuals and providing them with Zn supplementation, Cu chelation therapy and phlebotomy to eliminate Fe.",Copper/me [Metabolism];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/ge [Genetics];*Heterozygote;Humans;Iron/me [Metabolism];Monophenol Monooxygenase/me [Metabolism];Parkinson Disease/co [Complications];Parkinson Disease/en [Enzymology];*Parkinson Disease/ge [Genetics];Parkinson Disease/th [Therapy];Substantia Nigra/me [Metabolism];789U1901C5 (Copper);E1UOL152H7 (Iron);EC 1-14-18-1 (Monophenol Monooxygenase),"Johnson, S.",2001,Feb,https://dx.doi.org/10.1054/mehy.2000.1134,0,0,
505,Penicillamine-induced lethal status dystonicus in a patient with Wilson's disease,"A 37-year-old man with Wilson's disease is described, in whom the introduction of penicillamine therapy was followed after 3.5 weeks by the development of the status dystonicus with a fatal outcome.",Acute Kidney Injury/et [Etiology];Adult;Chelating Agents/ad [Administration & Dosage];*Chelating Agents/ae [Adverse Effects];Dystonia/ci [Chemically Induced];*Dystonia/co [Complications];Fatal Outcome;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];*Rhabdomyolysis/et [Etiology];Syndrome;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Svetel, M.;Sternic, N.;Pejovic, S.;Kostic, V. S.",2001,May,,0,0,
506,Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development,"The trace metal copper (Cu) plays an essential role in biology as a cofactor for many enzymes that include Cu, Zn superoxide dismutase, cytochrome oxidase, ceruloplasmin, lysyl oxidase, and dopamine beta-hydroxylase. Consequently, Cu transport at the cell surface and the delivery of Cu to intracellular compartments are critical events for a wide variety of biological processes. The components that orchestrate intracellular Cu trafficking and their roles in Cu homeostasis have been elucidated by the studies of model microorganisms and by the characterizations of molecular basis of Cu-related genetic diseases, including Menkes disease and Wilson disease. However, little is known about the mechanisms for Cu uptake at the plasma membrane and the consequences of defects in this process in mammals. Here, we show that the mouse Ctr1 gene encodes a component of the Cu transport machinery and that mice heterozygous for Ctr1 exhibit tissue-specific defects in copper accumulation and in the activities of copper-dependent enzymes. Mice completely deficient for Ctr1 exhibit profound growth and developmental defects and die in utero in mid-gestation. These results demonstrate a crucial role for Cu acquisition through the Ctr1 transporter for mammalian Cu homeostasis and embryonic development.","Animals;*Cation Transport Proteins;Cell Line;*Copper/me [Metabolism];*Embryonic and Fetal Development;Female;Homeostasis;Humans;Male;*Membrane Proteins/ph [Physiology];Mice;Mice, Inbred C57BL;Pregnancy;Saccharomyces cerevisiae/ge [Genetics];*Saccharomyces cerevisiae Proteins;0 (CTR1 protein, S cerevisiae);0 (Cation Transport Proteins);0 (Membrane Proteins);0 (SLC31A1 protein, human);0 (Saccharomyces cerevisiae Proteins);0 (Slc31a1 protein, mouse);0 (copper transporter 1);789U1901C5 (Copper)","Lee, J.;Prohaska, J. R.;Thiele, D. J.",2001,Jun 05,https://dx.doi.org/10.1073/pnas.111058698,0,0,
507,"Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson's disease?","Zinc has several crucial functions in brain development and maintenance: it binds to p53, preventing it from binding to supercoiled DNA and ensuring that p53 cause the expression of several paramount genes, such as the one that encodes for the type I receptors to pituitary adenine cylase-activator peptide (PACAP), which directs embryonic development of the brain cortex, adrenal glands, etc.; it is required for the production of CuZnSOD and Zn-thionein, which are essential to prevent oxidative damage; it is required for many proteins, some of them with Zn fingers, many of them essential enzymes for growth and homeostasis. For example, the synthesis of serotonin involves Zn enzymes and since serotonin is necessary for melatonin synthesis, a Zn deficiency may result in low levels of both hormones. Unfortunately, Zn levels tend to be low when there is excess Cu and Cd. Moreover, high estrogen levels tend to cause increased absorption of Cu and Cd, and smoking and eating food contaminated with Cd result in high levels of the latter. Furthermore, ethanol ingestion increases the elimination of Zn and Mg (which acts as a cofactor for CuZnSOD). Increased Cu levels may also be found in people with Wilson's disease, which is a rather rare disease. However, the heterozygote form (only one faulty copy of the chromosome) is not so rare. Therefore, the developing fetus of a pregnant women who is low in Zn and high in Cu may experience major difficulties in the early development of the brain, which may later manifest themselves as schizophrenia, autism or epilepsy. Similarly, a person who gradually accumulates Cu, will tend to experience a gradual depletion of Zn, with a corresponding increase in oxidative damage, eventually leading to Parkinson's disease. Also discussed are the crucial roles of histidine, histamine, vitamin D, essential fatty acids, vitamin E, peroxynitrate, etc. in the possible oxidative damage involved in these mental diseases. Copyright 2001 Harcourt Publishers Ltd.","*Autistic Disorder/me [Metabolism];Autistic Disorder/pp [Physiopathology];Brain/gd [Growth & Development];*Epilepsy/me [Metabolism];Epilepsy/pp [Physiopathology];Gene Expression Regulation/ph [Physiology];Genes, p53;Glucose/ph [Physiology];Humans;*Magnesium/ph [Physiology];Nitric Oxide/ph [Physiology];*Parkinson Disease/me [Metabolism];Parkinson Disease/pp [Physiopathology];Schizophrenia/co [Complications];*Schizophrenia/me [Metabolism];Schizophrenia/pp [Physiopathology];Smoking/ae [Adverse Effects];*Zinc/ph [Physiology];31C4KY9ESH (Nitric Oxide);I38ZP9992A (Magnesium);IY9XDZ35W2 (Glucose);J41CSQ7QDS (Zinc)","Johnson, S.",2001,May,https://dx.doi.org/10.1054/mehy.2000.1302,0,0,
508,Wilson's disease in pregnancy: five successful consecutive pregnancies of the same woman,"Wilson's disease is an autosomal recessive disorder of copper metabolism characterized mainly by liver cirrhosis and neurological disorders. Appropriate treatment with chelating agents allows normal fertility function. We report five consecutive successful pregnancies of the same woman, treated in the high-risk unit at our medical center. The management dilemmas and treatment options are discussed.","Alanine Transaminase/bl [Blood];Apgar Score;Aspartate Aminotransferases/bl [Blood];Chelating Agents/tu [Therapeutic Use];Female;Gestational Age;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;Penicillamine/tu [Therapeutic Use];Platelet Count;Pregnancy;*Pregnancy Complications;*Pregnancy Outcome;Risk Factors;0 (Chelating Agents);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine)","Furman, B.;Bashiri, A.;Wiznitzer, A.;Erez, O.;Holcberg, G.;Mazor, M.",2001,Jun,,0,0,
509,Wilson's disease with severe hepatic insufficiency: beneficial effects of early administration of D-penicillamine,"BACKGROUND: Wilson's disease, heralded by severe hepatic insufficiency, is a rare disorder for which emergency liver transplantation is considered to be the only effective therapy. AIMS: To report the features of Wilson's disease with severe hepatic insufficiency in a series of 17 patients and, during the second period of the study, to assess the efficacy of a policy consisting of early administration of D-penicillamine. PATIENTS: Seventeen consecutive patients with Wilson's disease were studied. During the first period of the study (up to 1979), none of the patients received D-penicillamine. During the second period (after 1979), all patients without encephalopathy at admission received D-penicillamine. RESULTS: The four patients observed during the first period who did not have encephalopathy at admission and did not receive D-penicillamine progressed to encephalopathy and died. Among the 13 consecutive patients observed during the second period, two patients with encephalopathy at admission did not receive D-penicillamine and were transplanted. The 11 remaining patients all received D-penicillamine. Ten of these patients survived without the need for transplantation and returned to compensated liver disease without liver insufficiency. In one patient, liver insufficiency progressed and transplantation had to be performed. CONCLUSIONS: In most patients with Wilson's disease heralded by severe hepatic insufficiency and without encephalopathy at admission, early administration of D-penicillamine was associated with survival without transplantation. These results suggest the importance of early diagnosis of this form of Wilson's disease before the onset of encephalopathy, and favour early administration of D-penicillamine which could avoid the need for transplantation in most cases.",Acute Kidney Injury/et [Etiology];Acute Kidney Injury/th [Therapy];Adolescent;Adult;*Chelating Agents/tu [Therapeutic Use];Child;Female;Hepatic Encephalopathy/et [Etiology];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation/mt [Methods];Male;Patient Selection;*Penicillamine/tu [Therapeutic Use];Treatment Outcome;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Durand, F.;Bernuau, J.;Giostra, E.;Mentha, G.;Shouval, D.;Degott, C.;Benhamou, J. P.;Valla, D.",2001,Jun,,1,1,
510,Surviving Wilson's disease,,"Adaptation, Psychological;Chelating Agents/tu [Therapeutic Use];Diagnostic Errors;Dimercaprol/tu [Therapeutic Use];Disease Progression;Drug Therapy, Combination;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/px [Psychology];*Hepatolenticular Degeneration;Humans;Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);0CPP32S55X (Dimercaprol);GNN1DV99GX (Penicillamine)","Yonetani, L.;Walshe, J. M.",2001,Jan-Feb,,0,0,
511,Treatment of Wilson's disease with zinc XVI: treatment during the pediatric years,"The objectives were to evaluate appropriate doses of zinc acetate and its efficacy for the maintenance management of Wilson's disease in pediatric cases. Pediatric patients of 1 to 5 years of age were given 25 mg of zinc twice daily; patients of 6 to 15 years of age, if under 125 pounds body weight, were given 25 mg of zinc three times daily; and patients 16 years of age or older were given 50 mg of zinc three times daily. Patients were followed for efficacy (or over-treatment) until their 19th birthday by measuring levels of urine and plasma copper, urine and plasma zinc and through liver function tests and quantitative speech and neurologic scores. Patients were followed for toxicity by measures of blood counts, blood biochemistries, urinalysis, and clinical follow-up. Thirty-four patients, ranging in ages from 3.2 to 17.7 years of age, were included in the study. All doses met efficacy objectives of copper control, zinc levels, neurologic improvement, and maintenance of liver function except for episodes of poor compliance. No instance of over-treatment was encountered. Four patients exhibited mild and transient gastric disturbance from the zinc. Zinc therapy in pediatric patients appears to have a mildly adverse effect on the high-density lipoprotein/total cholesterol ratio, contrary to results of an earlier large study of primarily adults. In conclusion, zinc is effective and safe for the maintenance management of pediatric cases of Wilson's disease. Our data are strongest in children above 10 years of age. More work needs to be done in very young children, and the cholesterol observations need to be studied further.","Adolescent;Age Factors;Age of Onset;Child;Child, Preschool;Copper/bl [Blood];Copper/ur [Urine];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Diseases/et [Etiology];Liver Diseases/pc [Prevention & Control];Male;*Zinc/ad [Administration & Dosage];789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Brewer, G. J.;Dick, R. D.;Johnson, V. D.;Fink, J. K.;Kluin, K. J.;Daniels, S.",2001,Mar,https://dx.doi.org/10.1067/mlc.2001.113037,0,0,
512,"Treatment of Wilson's disease: what are the relative roles of penicillamine, trientine, and zinc supplementation?","New options are available for the medical treatment of patients with Wilson's disease. Penicillamine is no longer the treatment of choice, as there is a growing experience with safer and more effective alternatives. Trientine may be the best choice for initial therapy in symptomatic patients requiring chelation therapy, and it may be even more effective when used in combination with zinc, which is recommended for maintenance therapy. Further studies are needed to determine the best therapy for pregnant patients with Wilson's disease, and whether combination therapy using trientine and zinc will be the next treatment of choice for all symptomatic patients with liver or neurologic disease. [References: 22]","Adenosine Triphosphatases/ai [Antagonists & Inhibitors];*Chelating Agents/tu [Therapeutic Use];Drug Therapy, Combination;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/tu [Therapeutic Use];*Penicillamine/tu [Therapeutic Use];Pregnancy;*Trientine/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];0 (Chelating Agents);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 3-6-1 (Adenosine Triphosphatases);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Schilsky, M. L.",2001,Feb,,0,0,
513,Wilson's disease,"Wilson's disease is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction of a copper transporting P-type ATPase encoded on chromosome 13. This ATPase is expressed in hepatocytes where it is localized to the trans-Golgi network and transports copper into the secretory pathway for incorporation into ceruloplasmin and excretion into the bile. Under physiologic circumstances, biliary excretion represents the sole mechanism for copper excretion, and thus affected individuals have progressive copper accumulation in the liver. When the capacity for hepatic storage is exceeded, cell death ensues with copper release into the plasma, hemolysis, and tissue deposition. Presentation in childhood may include chronic hepatitis, asymptomatic cirrhosis, or acute liver failure. In young adults, neuropsychiatric symptoms predominate and include dystonia, tremor, personality changes, and cognitive impairments secondary to copper accumulation in the central nervous system. The laboratory diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper content, and elevated hepatic copper concentration. Molecular genetic analysis is complex as more than 100 unique mutations have been identified and most individuals are compound heterozygotes. Copper chelation with penicillamine is an effective therapy in most patients and hepatic transplantation is curative in individuals presenting with irreversible liver failure. Elucidation of the molecular genetic basis of Wilson's disease has permitted new insights into the mechanisms of cellular copper homeostasis. [References: 106]",Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Adult;Carrier Proteins/ge [Genetics];Carrier Proteins/me [Metabolism];*Cation Transport Proteins;Chelating Agents/tu [Therapeutic Use];Child;Copper/me [Metabolism];Hepatocytes/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration;Humans;Immunoblotting;Liver/me [Metabolism];Penicillamine/tu [Therapeutic Use];0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine),"Loudianos, G.;Gitlin, J. D.",2000,,https://dx.doi.org/10.1055/s-2000-9389,0,0,
514,"The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients","UNLABELLED: The aim of this study was to estimate the level of lipids and of the main serum antioxidant, alpha-tocopherol (vitamin E), and to evaluate the susceptibility of low density lipoprotein (LDL) to oxidation in Wilson's disease patients. It was assumed that enhanced LDL peroxidation caused by high copper levels could contribute to the injury of liver and other tissues. The group investigated comprised 45 individuals with Wilson's disease treated with penicillamine or zinc salts and a control group of 36 healthy individuals. Lipids were determined by enzymatic methods, alpha-tocopherol by high performance liquid chromatography, the susceptibility of LDL to oxidation in vitro by absorption changes at 234 nm during 5 h and end-products of LDL lipid oxidation as thiobarbituric acid reacting substances. In Wilson's disease patients total cholesterol, LDL cholesterol and alpha-tocopherol levels were significantly lower compared with the control group. No difference in LDL oxidation in vitro between the patients and the controls was stated. CONCLUSION: enhanced susceptibility of isolated LDL for lipid peroxidation in vitro was not observed in Wilson's disease patients. One cannot exclude, however, that because of low alpha-tocopherol level lipid peroxidation in the tissues can play a role in the pathogenesis of tissue injury in this disease.","Adult;Cholesterol/bl [Blood];Copper/bl [Blood];*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lipid Peroxidation/ph [Physiology];*Lipoproteins, LDL/bl [Blood];Middle Aged;Penicillamine/ad [Administration & Dosage];Treatment Outcome;Triglycerides/bl [Blood];*Vitamin E/bl [Blood];Zinc Sulfate/ad [Administration & Dosage];0 (Lipoproteins, LDL);0 (Triglycerides);1406-18-4 (Vitamin E);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);97C5T2UQ7J (Cholesterol);GNN1DV99GX (Penicillamine)","Rodo, M.;Czonkowska, A.;Pulawska, M.;Swiderska, M.;Tarnacka, B.;Wehr, H.",2000,Sep,,0,0,
515,Penicillamine induced lupus-like syndrome: a case report,"Several drugs have been suggested to cause lupus-like syndrome. However, penicillamine-induced lupus-like syndrome has only rarely been reported in patients with Wilson's disease. We describe a 6- year-old Taiwanese girl, with a diagnosis of Wilson's disease in November, 1997, who developed lupus-like syndrome 17 months after penicillamine treatment. After treatment with prednisolone and decrease in the dose of penicillamine, her symptoms subsided gradually. This is the first such case reported in a Taiwanese patient. Because the symptoms of drug-induced lupus (DIL) are nonspecific, subjective and variable, the diagnosis of DIL requires awareness of DIL-inducing potential of chronic medication.","Child;Female;Humans;*Lupus Erythematosus, Systemic/ci [Chemically Induced];Lupus Erythematosus, Systemic/di [Diagnosis];*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine)","Lin, H. C.;Hwang, K. C.;Lee, H. J.;Tsai, M. J.;Ni, Y. H.;Chiang, B. L.",2000,Sep,,0,0,
516,Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson's disease,,Acute Disease;Adult;*Chemical and Drug Induced Liver Injury/et [Etiology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications/dt [Drug Therapy];*Zinc/ae [Adverse Effects];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Castilla-Higuero, L.;Romero-Gomez, M.;Suarez, E.;Castro, M.",2000,Oct,https://dx.doi.org/10.1053/jhep.2000.17917,0,0,
517,Cellular copper transport and metabolism,"The transport and cellular metabolism of Cu depends on a series of membrane proteins and smaller soluble peptides that comprise a functionally integrated system for maintaining cellular Cu homeostasis. Inward transport across the plasma membrane appears to be a function of integral membrane proteins that form the channels that select Cu ions for passage. Two membrane-bound Cu-transporting ATPase enzymes, ATP7A and ATP7B, the products of the Menkes and Wilson disease genes, respectively, catalyze an ATP-dependent transfer of Cu to intracellular compartments or expel Cu from the cell. ATP7A and ATP7B work in concert with a series of smaller peptides, the copper chaperones, that exchange Cu at the ATPase sites or incorporate the Cu directly into the structure of Cu-dependent enzymes such as cytochrome c oxidase and Cu, Zn superoxide dismutase. These mechanisms come into play in response to a high influx of Cu or during the course of normal Cu metabolism. [References: 153]",Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Albumins/ph [Physiology];Biological Transport;*Carrier Proteins/ph [Physiology];Ceruloplasmin/ph [Physiology];*Copper/me [Metabolism];Copper/ph [Physiology];Copper/tu [Therapeutic Use];Glutathione/ph [Physiology];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];*Liver/me [Metabolism];Menkes Kinky Hair Syndrome/ge [Genetics];Menkes Kinky Hair Syndrome/me [Metabolism];0 (Albumins);0 (Carrier Proteins);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-6-1 (Adenosine Triphosphatases);GAN16C9B8O (Glutathione),"Harris, E. D.",2000,,https://dx.doi.org/10.1146/annurev.nutr.20.1.291,0,0,
518,Procreation ability in Wilson's disease,"OBJECTIVES: The clinical manifestations of Wilson's disease (WD) take the form of hepatic, neurological, renal as well as hormonal disturbances. Infertility and amenorrhea are reported in women and hypogonadism in men with WD. Our study was designed to analyse the procreation abilities of patients with WD. MATERIAL AND METHODS: We investigated by a questionnaire the course of pregnancy and delivery in 31 untreated women (mean age 22.5 years, 82 pregnancies) and 15 women (mean age 26.2, 25 pregnancies,) treated with D-penicillamine (D-p) or zinc sulphate (ZnS). We studied also procreation ability of 27 men (mean age 27.2 years). We analysed the congenital abnormalities and frequency of WD in children of our patients. RESULTS: One of 10 untreated women had difficulties with conception. The number and type of pathology (imminent abortions, gestosis, stillbirth, preterm births) were similar in treated and untreated patients. In both mentioned groups the most frequent pathology were spontaneous abortions, which were found in 26% of untreated and in 26.6% of treated women. This percentage is higher than in general population. Most of deliveries in patients with WD were spontaneous. Neither developmental malformations nor serious disorders were noticed in the offspring of our treated patients, 3 children of untreated patients were born with congenital heart disease. In 78 of the 110 children of our patients we examined the copper metabolism and we diagnosed WD in 5 cases (from 3 families). Among 27 investigated men only 1 was impotent. CONCLUSION: The risk of complications during pregnancy in asymptomatic and treated patients is higher than in general population, but it does not make the procreation impossible.",Adolescent;Adult;Erectile Dysfunction/et [Etiology];Erectile Dysfunction/pp [Physiopathology];Female;*Fertility/ph [Physiology];*Gonadal Disorders/et [Etiology];Gonadal Disorders/pp [Physiopathology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Middle Aged;Pregnancy;Pregnancy Complications/et [Etiology];Pregnancy Complications/pp [Physiopathology],"Tarnacka, B.;Rodo, M.;Cichy, S.;Czlonkowska, A.",2000,Jun,,0,0,
519,Wilson's disease--early onset and lessons from a pediatric cohort in India,"OBJECTIVE: To study the clinical profile at presentation and on follow up in cases of Wilson's disease presenting at this hospital. METHODS: Case records of children diagnosed as Wilson's disease (WD) admitted in the hospital or attending the Pediatric outpatient department were retrospectively studied with regard to clinical features, investigations, and family screening at the time of presentation. Note was made of the treatment received by the patients. Clinical profile on follow up was recorded with respect to side effects of treatment, and whether patient improved, deteriorated or remained the same, either from the records or by calling the patient for a follow up, if possible. RESULTS: Analysis of 25 children with Wilson's disease comprising 19 index cases and 6 siblings detected on family screening, revealed mean age of onset for the hepatic presentation was 6.8 years versus 8 years for the neurologic patient. A quarter of index cases has a family history strongly suspicious for Wilson disease which has been earlier overlooked. Clinical presentation was hepatic in 5 patients, purely neurologic in 5, mixed hepatic and neurologic in 9, hemolytic anemia in 1 and polyarthritis in 1. Patients received treatment with D penicillamine, zinc, pyridoxine and low copper diet. Follow upon 18 patients revealed improvement in majority, residual dysarthria in seven,prolonged persistence of KF rings in 15 and complications like renal tubular acidosis with osteopenia in one. CONCLUSION: The early age of onset of symptoms, prolonged KF rings persistence and progression of symptoms among sibs despite therapy is of interest as it may be related to a high copper intake, which may be due to the practice of using brass or copper utensils for cooking Since a large number of children has either a past history of jaundice or sibling deaths due to jaundice or cirrhosis, a high index of suspicion and screening for KF rings is emphasized as a simple and cost effective way of detecting a curable disease at an early stage and family screening of all index cases is imperative. Progression of symptoms among sibs on oral zinc and low dose pencillamine suggests inadequacy of zinc alone for prophylaxis.","Adolescent;Age of Onset;Child;Child, Preschool;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/th [Therapy];Humans;India","Kalra, V.;Khurana, D.;Mittal, R.",2000,Jun,,0,1,
520,Visual pathway abnormalities Wilson's disease: an electrophysiological study using electroretinography and visual evoked potentials,"The pathogenesis of the pattern reversal visual evoked potential (PRVEP) abnormalities in patients with Wilson's disease (WD) has not been investigated earlier. Since electroretinography (ERG) assesses the functional integrity of the retina, it was used along with PRVEP to localize the abnormalities in PRVEP in Wilson's patients. Ten newly diagnosed Wilson's disease patients underwent PRVEP and flash ERG soon after the diagnosis was established. The PRVEP latencies were prolonged in comparison with the controls (P<0.001). Photopic and scotopic A waves and oscillatory potentials were prolonged (P<0. 02) with reduction in amplitudes of photopic A and B waves (P<0.001). Six of these patients were subjected to repeat PRVEP and flash ERG after the clinical improvement with specific therapy. Comparison of the pre and post-treatment visual electrophysiological studies revealed significant reduction in latencies of PRVEP and flash ERG A wave (P<0.05) with increase in amplitudes of P100 of PRVEP (P<0.05), A and B waves of flash ERG (P<0.01). These findings confirm the reported PRVEP changes in WD and in addition demonstrate the reversibility of the retinal dysfunction which partially contributes to the PRVEP abnormalities. To the best of our knowledge this is the first study of ERG in patients with Wilson's disease in the literature. Further, there have been no earlier reports in the literature evaluating the effect of specific treatment on the PRVEP and ERG in Wilson's disease.","Adolescent;Adult;Chelation Therapy;Child;Copper/me [Metabolism];Drug Therapy, Combination;Electroretinography/de [Drug Effects];*Electroretinography;Evoked Potentials, Visual/de [Drug Effects];*Evoked Potentials, Visual/ph [Physiology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Penicillamine/tu [Therapeutic Use];Retina/pp [Physiopathology];Sulfides/tu [Therapeutic Use];*Visual Pathways/pp [Physiopathology];Zinc Sulfate/tu [Therapeutic Use];0 (Sulfides);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Satishchandra, P.;Ravishankar Naik, K.",2000,May 01,,0,0,
521,Inhibition of carboxypeptidase A by D-penicillamine: mechanism and implications for drug design,"Zinc metalloprotease inhibitors are usually designed to inactivate the enzyme by forming a stable ternary complex with the enzyme and active-site zinc. D-Cysteine inhibits carboxypeptidase, ZnCPD, by forming such a complex, with a K(i) of 2.3 microM. In contrast, the antiarthritis drug D-penicillamine, D-PEN, which differs from D-Cys only by the presence of two methyl groups on the beta-carbon, inhibits ZnCPD by promoting the release of the active-site zinc. We have given the name catalytic chelator to such inhibitors. Inhibition is a two-step process characterized by formation of a complex with the enzyme (K(i(initial)) = 1.2 mM) followed by release of the active-site zinc at rates up to 420-fold faster than the spontaneous release. The initial rate of substrate hydrolysis at completion of the second step also depends on D-PEN concentration, reflecting formation of a thermodynamic equilibrium governed by the stability constants of chelator and apocarboxypeptidase for zinc (K(i(final)) = 0.25 mM). The interaction of D-PEN and D-Cys with the active-site metal has been examined by replacing the active-site zinc by a chromophoric cobalt atom. Both inhibitors perturb the d-d transitions of CoCPD in the 500-600 nm region within milliseconds of mixing but only the CoCPD.D-Cys complex displays a strong S --> Co(II) charge-transfer band at 340 nm indicative of a metal-sulfur bond. While the D-Cys complex is stable, the CoCPD.D-PEN complex breaks down to apoenzyme and Co(D-PEN)(2) with a half-life of 0.5 s. D-PEN is the first drug found to inhibit a metalloprotease by increasing the dissociation rate constant of the active-site metal. The ability of D-PEN to catalyze metal removal from carboxypeptidase A and other zinc proteases suggests a possible mechanism of action in arthritis and Wilson's disease and may also underlie complications associated with its clinical use.",*Carboxypeptidases/ai [Antagonists & Inhibitors];Carboxypeptidases A;*Drug Design;*Enzyme Inhibitors/pd [Pharmacology];Hydrolysis;*Penicillamine/pd [Pharmacology];Spectrum Analysis;Substrate Specificity;0 (Enzyme Inhibitors);EC 3-4 (Carboxypeptidases);EC 3-4-17-1 (Carboxypeptidases A);GNN1DV99GX (Penicillamine),"Chong, C. R.;Auld, D. S.",2000,Jun 27,,0,0,
522,Wilson's disease with superimposed autoimmune features: report of two cases and review,"We describe two females, 15 and 23 years old, respectively, who presented with classical features of Wilson's disease (WD) and several features of autoimmune hepatitis (AIH). The first patient was initially diagnosed as AIH and treated with prednisolone which caused clinical improvement, with an increase of serum albumin from 22 to 30 g/L, and a decrease of aspartate aminotransferase from 103 to 47 U/L. Subsequent diagnosis of WD and introduction of penicillamine gave excellent improvement and complete normalization of liver function tests. The second patient, at first also diagnosed as having AIH, was treated with steroids and azathioprine with initial improvement, but subsequent deterioration. The diagnosis of WD was made 2 years after initial diagnosis of AIH, as the patient reached end-stage liver disease and required a transplant. Therefore, d-penicillamine treatment was not attempted. We conclude that, in patients with AIH, a thorough screening for WD is necessary, particularly when the response to steroid therapy is poor. Conversely, in patients suffering from WD with superimposed features of AIH, a combination of steroids and penicillamine may be of benefit. [References: 17]","Adolescent;Adult;Azathioprine/tu [Therapeutic Use];Copper/an [Analysis];Diagnostic Errors;Female;Glucocorticoids/tu [Therapeutic Use];*Hepatitis, Autoimmune/co [Complications];Hepatitis, Autoimmune/dt [Drug Therapy];*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Humans;Immunosuppressive Agents/tu [Therapeutic Use];Liver/pa [Pathology];Penicillamine/tu [Therapeutic Use];Prednisolone/tu [Therapeutic Use];0 (Glucocorticoids);0 (Immunosuppressive Agents);789U1901C5 (Copper);9PHQ9Y1OLM (Prednisolone);GNN1DV99GX (Penicillamine);MRK240IY2L (Azathioprine)","Milkiewicz, P.;Saksena, S.;Hubscher, S. G.;Elias, E.",2000,May,,0,0,
523,Copper transport and its defect in Wilson disease: characterization of the copper-binding domain of Wilson disease ATPase,"Copper is an essential trace element which forms an integral component of many enzymes. While trace amounts of copper are needed to sustain life, excess copper is extremely toxic. An attempt is made here to present the current understanding of the normal transport of copper in relation to the absorption, intracellular transport and toxicity. Wilson disease is a genetic disorder of copper transport resulting in the accumulation of copper in organs such as liver and brain which leads to progressive hepatic and neurological damage. The gene responsible for Wilson disease (ATP7B) is predicted to encode a putative copper-transporting P-type ATPase. An important feature of this ATPase is the presence of a large N-terminal domain that contains six repeats of a copper-binding motif which is thought to be responsible for binding this metal prior to its transport across the membrane. We have cloned, expressed and purified the N-terminal domain (approximately 70 kD) of Wilson disease ATPase. Metal-binding properties of the domain showed the protein to bind several metals besides copper; however, copper has a higher affinity for the domain. The copper is bound to the domain in Cu(I) form with a copper: protein ratio of 6.5:1. X-ray absorption studies strongly suggest Cu(I) atoms are ligated to cysteine residues. Circular dichroism spectral analyses suggest both secondary and tertiary structural changes upon copper binding to the domain. Copper-binding studies suggest some degree of cooperativity in binding of copper. These studies as well as detailed structural information of the copper-binding domain will be crucial in determining the specific role played by the copper-transporting ATPase in the homeostatic control of copper in the body and how the transport of copper is interrupted by mutations in the ATPase gene.","*Adenosine Triphosphatases/ch [Chemistry];*Adenosine Triphosphatases/me [Metabolism];Amino Acid Sequence;Binding Sites;*Carrier Proteins/ch [Chemistry];*Carrier Proteins/me [Metabolism];*Cation Transport Proteins;Cell Membrane/en [Enzymology];Circular Dichroism;*Copper/me [Metabolism];*Hepatolenticular Degeneration/me [Metabolism];Humans;Kinetics;Models, Molecular;Molecular Sequence Data;Protein Structure, Secondary;Protein Structure, Tertiary;Recombinant Fusion Proteins/me [Metabolism];Zinc/me [Metabolism];0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Recombinant Fusion Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc)","Sarkar, B.",2000,Apr,,0,0,
524,"CSF copper concentrations, blood-brain barrier function, and coeruloplasmin synthesis during the treatment of Wilson's disease","During the treatment of four patients with cerebral manifestation of Wilson's disease, we measured the copper concentration in the cerebrospinal fluid (CSF) and serum, the serum coeruloplasmin concentration, the free copper concentration in the serum, and the albumin ratio CSF/serum (AR). These measurements were treated as indicators of the copper-related toxic effects on the brain and the blood-brain barrier (BBB). The half-life of the decrease in the CSF copper concentration during therapy was 23.5 +/- 5.78 months (mean +/- S.E.M.). The therapeutic-target-copper concentration in the CSF (mean normal concentration) is below 20 microg/l. The average length of therapy needed to normalize CSF-copper values in our patients with an average initial value of 76.25 microg/L was 47 month. During the first 10 month of treatment there was an increase in all cases of the measured disturbance in the blood-brain barrier (measured as the ratio of albumin in CSF to albumin in serum, AR). All patients showed an initial worsening of the neurological condition, on average after 1.75 +/- 0.25 months. The maximal rise in AR, from the initial values, was on average 18.4 +/- 5.08%; this maximum was reached after an average of 6.9 +/- 1.5 months. The AR normalized during therapy, indicating a reduction in toxicity in the blood-brain barrier region. The extent of the AR increases in individual patients did not correlate significantly with CSF copper half-life, serum copper half-life, the initial half-life of the reduction in the ratio (copper in serum)/(coeruloplasmin in serum), the initial copper concentration in CSF or serum, the initial free copper concentration in serum, or the initial dose of penicillamine (within the first 2 months). We conclude that the normalization of the CSF copper concentration in patients with the cerebral manifestation of Wilson's disease is a slow process, even if therapy is sufficient. The initial worsening of the neurological condition which has often been reported may be reflected in the disturbance of blood-brain barrier function, which we have measured here for the first time (using the parameter of the albumin ratio CSF/serum). Based on repeated measurements of the AR during the course of treatment it seems that the brain toxicity of mobilized copper can be assessed and the therapy adjusted.",Adult;*Blood-Brain Barrier/ph [Physiology];Brain/me [Metabolism];Cerebrovascular Circulation/ph [Physiology];*Ceruloplasmin/bi [Biosynthesis];*Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];*Copper/cf [Cerebrospinal Fluid];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/cf [Cerebrospinal Fluid];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];Serum Albumin/cf [Cerebrospinal Fluid];Serum Albumin/pk [Pharmacokinetics];Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);0 (Serum Albumin);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Stuerenburg, H. J.",2000,,https://dx.doi.org/10.1007/s007020050026,0,0,
525,Neuro/Images. Kayser-Fleischer corneal ring,,Adult;*Corneal Diseases/di [Diagnosis];Corneal Diseases/dt [Drug Therapy];Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];*Pigmentation Disorders/di [Diagnosis];Pigmentation Disorders/dt [Drug Therapy];GNN1DV99GX (Penicillamine),"Heckmann, J. G.;Lang, C. J.;Neundorfer, B.;Kuchle, M.",2000,May 09,,0,0,
526,Pencillamine-induced elastosis perforans serpiginosa and cutis laxa in Wilson's disease,,Adult;*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];*Cutis Laxa/ci [Chemically Induced];Elastic Tissue;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Skin Diseases/ci [Chemically Induced];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Hill, V. A.;Seymour, C. A.;Mortimer, P. S.",2000,Mar,,0,0,
527,Hypersomnia in Wilson's disease: an unusual symptom in an unusual case,"Wilson's disease (WD) shows a wide heterogeneity in symptoms. In this case report we present hypersomnia as a symptom of WD. The male patient's complaints as fatigue, decreased level of concentration, and highly increased demand of sleeping started at his age of 21 years. No abnormality was found at physical examination. A moderate elevation in liver function tests was found, but all the other laboratory findings were within the normal range. The marked hypersomnia was verified by 24-h cassette EEG polisomnographic monitoring. No abnormality was found at physical examination. EEG, brain CT and MRI were normal. Neither toxic nor infectious disease was detectable. The diagnosis of WD was based on decreased coeruloplasmin level, increased baseline and forced urinary excretion of copper, and decreased level of serum copper. Kayser-Fleischer ring was not detectable. D-penicillamine (DPA) was introduced. At 8-10 months after the initiation of the therapy the patient's complaints gradually resolved. The control sleep record 14 months after the initiation of the DPA therapy was normal. Five years later the patient is currently on penicillamine treatment and he is free of any symptom.","Adult;Ceruloplasmin/me [Metabolism];Copper/bl [Blood];Copper/ur [Urine];Diagnosis, Differential;*Disorders of Excessive Somnolence/et [Etiology];Fatigue/et [Etiology];*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver Function Tests;Male;Penicillamine/tu [Therapeutic Use];Polysomnography;Treatment Outcome;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Firneisz, G.;Szalay, F.;Halasz, P.;Komoly, S.",2000,Apr,,0,0,
528,Wilson's disease with hepatic presentation in childhood,"OBJECTIVE: To evaluate clinical, laboratory findings, treatment and long-term follow-up of children with Wilson's disease with hepatic presentation. DESIGN: Retrospective study with a median follow-up period of 9 years. SETTING: University medical center. SUBJECTS: Thirty-four children with hepatic involvement, ranging in age from three to fifteen years, were diagnosed as Wilson's disease over an eighteen year period. METHODS: The diagnosis was based on the presence of family history and Kayser-Fleischer rings, low serum ceruloplasmin levels and increased urinary and hepatic copper concentrations. RESULTS: Four patients had also neurological manifestations. Eight patients were diagnosed as fulminating hepatic failure resulting in death in a few days. The most common symptoms were abdominal distension and abdominal pain. Hepatomegaly was the predominant physical finding and serum transaminases were elevated in most of the patients. Twenty patients had cirrhosis and six had chronic hepatitis histopathologically. All patients with fulminating hepatic failure had hyperbilirubinemia with normal alkaline phosphatase and higher aspartate aminotransferase than alanine aminotransferase. Patients were treated with D-penicillamine and zinc sulphate. Three patients underwent liver transplantation. Four more patients besides patients with fulminating hepatic failure died due to end stage liver disease. Twenty-two patients were followed for median 9 years. Four patients with poor compliance progressed to decompensated cirrhosis and the others were stable. CONCLUSIONS: Liver disease with unknown origin with positive family history and parental consanguinity should imply Wilson's disease strongly.","Adolescent;Age of Onset;Child;Child, Preschool;Consanguinity;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/mo [Mortality];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;India/ep [Epidemiology];Liver/pa [Pathology];Liver Cirrhosis/ep [Epidemiology];Liver Cirrhosis/et [Etiology];Liver Failure/ep [Epidemiology];Liver Failure/et [Etiology];Male;Retrospective Studies;Statistics, Nonparametric","Yuce, A.;Kocak, N.;Gurakan, F.;Ozen, H.",2000,Jan,,0,1,
529,"Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study","Preclinical and in vitro studies have determined that copper is an important cofactor for angiogenesis. Tetrathiomolybdate (TM) was developed as an effective anticopper therapy for the initial treatment of Wilson's disease, an autosomal recessive disorder that leads to abnormal copper accumulation. Given the potency and uniqueness of the anticopper action of TM and its lack of toxicity, we hypothesized that TM would be a suitable agent to achieve and maintain mild copper deficiency to impair neovascularization in metastatic solid tumors. Following preclinical work that showed efficacy for this anticopper approach in mouse tumor models, we carried out a Phase I clinical trial in 18 patients with metastatic cancer who were enrolled at three dose levels of oral TM (90, 105, and 120 mg/day) administered in six divided doses with and in-between meals. Serum ceruloplasmin (Cp) was used as a surrogate marker for total body copper. Because anemia is the first clinical sign of copper deficiency, the goal of the study was to reduce Cp to 20% of baseline value without reducing hematocrit below 80% of baseline. Cp is a reliable and sensitive measure of copper status, and TM was nontoxic when Cp was reduced to 15-20% of baseline. The level III dose of TM (120 mg/ day) was effective in reaching the target Cp without added toxicity. TM-induced mild copper deficiency achieved stable disease in five of six patients who were copper deficient at the target range for at least 90 days.","Adult;Angiogenesis Inhibitors/ad [Administration & Dosage];*Angiogenesis Inhibitors/ae [Adverse Effects];Animals;Biomarkers/bl [Blood];Ceruloplasmin/an [Analysis];Copper/bl [Blood];Copper/df [Deficiency];Dose-Response Relationship, Drug;Drug Administration Schedule;Female;Humans;Male;Mice;Middle Aged;Molybdenum/ad [Administration & Dosage];*Molybdenum/ae [Adverse Effects];Neoplasm Metastasis;*Neoplasms/dt [Drug Therapy];Neoplasms/pa [Pathology];0 (Angiogenesis Inhibitors);0 (Biomarkers);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-16-3-1 (Ceruloplasmin)","Brewer, G. J.;Dick, R. D.;Grover, D. K.;LeClaire, V.;Tseng, M.;Wicha, M.;Pienta, K.;Redman, B. G.;Jahan, T.;Sondak, V. K.;Strawderman, M.;LeCarpentier, G.;Merajver, S. D.",2000,Jan,,0,0,
530,Wilson's disease and pregnancy,,*Chelating Agents/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications/dt [Drug Therapy];Pregnancy Outcome;*Trientine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Sternlieb, I.",2000,Feb,https://dx.doi.org/10.1002/hep.510310239,0,0,
531,"Recognition, diagnosis, and management of Wilson's disease","Wilson's disease is a relatively rare inherited disorder of copper accumulation and toxicity, caused by a defect in an enzyme that is part of the pathway of biliary excretion of excess copper. Clinically, patients usually present as older children or young adults with hepatic, neurologic, or psychiatric manifestations, or some combination of these. Wilson's disease is unusual among genetic diseases in that it can be very effectively treated. The prevention of severe permanent damage depends upon early recognition and diagnosis by the physician, followed by appropriate anticopper treatment. Anticopper treatments have evolved considerably since the days when the only drug available was penicillamine. Zinc is now the recommended therapy for long-term management of the disease. [References: 57]",Adolescent;Adult;*Chelating Agents/tu [Therapeutic Use];Child;Copper/me [Metabolism];*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Brewer, G. J.",2000,Jan,,0,0,
532,Diagnosis and treatment of Wilson's disease,"Wilson's disease is due to an inherited defect in copper excretion into the bile by the liver. The resulting copper accumulation and copper toxicity results in liver disease, and in some patients, brain damage. Patients present, generally between the ages of 10 and 40 years, with liver disease, neurological disease of a movement disorder type, or behavioral abnormalities, and often with a combination of these. Because Wilson's disease is effectively treated, it is extremely important for physicians to learn to recognize and diagnose the disease. Treatment options have evolved rapidly in the last few years, with zinc now being the drug of choice in most situations. [References: 66]",Adenosine Triphosphatases/ge [Genetics];Cation Transport Proteins/ge [Genetics];Copper/ai [Antagonists & Inhibitors];Copper/me [Metabolism];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Diseases/et [Etiology];Mutation;Nervous System Diseases/et [Etiology];0 (Cation Transport Proteins);789U1901C5 (Copper);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein),"Brewer, G. J.;Fink, J. K.;Hedera, P.",1999,,https://dx.doi.org/10.1055/s-2008-1040842,0,0,
533,Generalized myasthenia gravis following use of D-pencillamine in Wilson's disease,,Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Myasthenia Gravis/ci [Chemically Induced];Myasthenia Gravis/di [Diagnosis];*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Narayanan, C. S.;Behari, M.",1999,Jun,,0,0,
534,"Psychiatric symptoms as late onset of Wilson's disease: neuroradiological findings, clinical features and treatment","We describe a case of Wilson's disease with late psychiatric onset. Major depressive disorder was the first clinical manifestation at the age of 38 years. After pharmacotherapy with antidepressive agents, a manic episode was observed. Extrapyramidal hand tremor and micrography were the first neurological signs. Emotional lability occurred during worsening of extrapyramidal signs. Diagnosis was based on urinary and serum copper levels, ceruloplasmin serum level, Kayser-Fleischer ring, and liver biopsy that detected cirrhosis. Magnetic resonance imaging revealed basal ganglia hyperintensity on T1-weighted images, and hypodensity in the central part and hyperintensity in the peripheral part of the lentiform nucleus on T2-weighted images. Hyperintensity on T2-weighted images was also observed in the dorsal part of the midbrain. 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) detected a normal distribution of the drug in the brain, with better signal in the right side and deficit of D2-dopaminergic receptors in the basal ganglia. Abnormal manganese erythrocyte level was observed. Treatment was based on penicillamine, zinc salts, low-copper diet, antidepressant agents, interpersonal psychotherapy and neurorehabilitation.","Adult;Age of Onset;Antidepressive Agents/ae [Adverse Effects];Antidepressive Agents/tu [Therapeutic Use];Basal Ganglia/ch [Chemistry];Basal Ganglia Diseases/di [Diagnosis];*Basal Ganglia Diseases/et [Etiology];Biopsy;Bipolar Disorder/ci [Chemically Induced];*Bipolar Disorder/di [Diagnosis];*Bipolar Disorder/et [Etiology];Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Ceruloplasmin/an [Analysis];Combined Modality Therapy;Copper/an [Analysis];*Depressive Disorder, Major/et [Etiology];*Diagnostic Errors;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ep [Epidemiology];*Hepatolenticular Degeneration/px [Psychology];Humans;Lithium Carbonate/tu [Therapeutic Use];Liver/pa [Pathology];Liver Cirrhosis/di [Diagnosis];Liver Cirrhosis/et [Etiology];Liver Cirrhosis/pa [Pathology];Mmpi;Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];Receptors, Dopamine D2/df [Deficiency];Tomography, Emission-Computed, Single-Photon;Tremor/di [Diagnosis];Tremor/et [Etiology];Zinc/tu [Therapeutic Use];0 (Antidepressive Agents);0 (Receptors, Dopamine D2);2BMD2GNA4V (Lithium Carbonate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Keller, R.;Torta, R.;Lagget, M.;Crasto, S.;Bergamasco, B.",1999,Feb,,0,0,
535,Steroids used to desensitize penicillamine allergy in Wilson disease,"Patients with Wilson disease require life-long treatment and penicillamine is the drug of choice. We present a 14-year-old boy with Wilson disease who developed hypersensitivity reaction 2 days after starting penicillamine therapy. His symptoms included fever, maculopapular rash and lip edema. The allergic reaction disappeared when penicillamine was discontinued, but relapsed after reinstituting penicillamine at a lower dose. Desensitization was attempted by introducing steroid therapy, the dose of 0.7 mg per kilogram per day of prednisolone for 2 days, then penicillamine was successfully tolerated. Subsequent tapering of the daily prednisolone dose was performed till it was discontinued one month after treatment began. We suggest that concomitant use of steroid and penicillamine should be used for the treatment of patients who develop penicillamine intolerance.",Adolescent;*Drug Hypersensitivity/dt [Drug Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];*Prednisolone/tu [Therapeutic Use];9PHQ9Y1OLM (Prednisolone);GNN1DV99GX (Penicillamine),"Hsu, H. L.;Huang, F. C.;Ni, Y. H.;Chang, M. H.",1999,Nov-Dec,,0,0,
536,Magnetic resonance imaging and proton MR spectroscopy in Wilson's disease,"MRI of the brain and liver using T2 relaxation time measurements and proton spectroscopy (1H-MRS) of the brain was performed in four siblings with Wilson's disease (one with clinical disease and three asymptomatic) as well as age- and sex-matched control subjects. The T2 values of the liver were correlated with liver biopsy results. 1H-MRS of the left and right globus pallidus was obtained. The patient with clinical disease was examined three times, and two of three asymptomatic siblings twice. MR images of the brain were abnormal in all four patients. High signal intensity areas in the posterior thalamus, general atrophy and pontine myelinolysis were present in the patient with clinical manifestations. The T2 measurements of these areas confirmed the results of image analysis. Apart from general brain atrophy, the changes in the patient with clinical disease were largely reversible. The T2 values were significantly different from those of the control subjects only in the globus pallidus. The NAA/Cho, NAA/Cr and Cho/Cr ratios from the 1H-MR spectra of globus pallidus showed no significant difference between patients and control subjects. The mean values of NAA/Cho and NAA/Cr were lower in patients with Wilson's disease than in the control subjects. One of the patients had hepatic steatosis, but the liver T2 values were no different to those of the control subjects. In conclusion, the MRI findings reflect the success of the specific therapy in patients. MRI thus seems to be useful in the follow-up of Wilson's disease.",Adult;*Basal Ganglia/pa [Pathology];Case-Control Studies;Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver/pa [Pathology];*Magnetic Resonance Imaging;*Magnetic Resonance Spectroscopy;Penicillamine/tu [Therapeutic Use];Sensitivity and Specificity;GNN1DV99GX (Penicillamine),"Alanen, A.;Komu, M.;Penttinen, M.;Leino, R.",1999,Aug,https://dx.doi.org/10.1259/bjr.72.860.10624340,0,0,
537,Potential hepatotoxicity of penicillamine treatment in three patients with Wilson's disease,,*Chelating Agents/ae [Adverse Effects];*Chemical and Drug Induced Liver Injury;Child;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Deutscher, J.;Kiess, W.;Scheerschmidt, G.;Willgerodt, H.",1999,Nov,,0,0,
538,Liver transplantation for Wilson's disease: a single-center experience,"Wilson's disease is a hereditary defect in copper excretion leading to the accumulation of copper in the tissues, with subsequent tissue damage. The most serious sequela is that of progressive central nervous system involvement. The use of orthotopic liver transplantation (OLT) has been controversial for those patients with neurological symptoms attributed to Wilson's disease. The aim of this study is to determine the effectiveness of OLT for patients with Wilson's disease, including those with neurological involvement attributed to copper accumulation in the central nervous system. OLT was performed in 45 patients (19 men [42.2%], 26 women [57.8%]) with Wilson's disease between 1971 and 1993 who were followed up for at least 4 years. The age at diagnosis of Wilson's disease ranged from 3 to 41 years (mean, 17.7 +/- 7.4 years). The age at OLT ranged from 8 to 52 years (mean, 22.3 +/- 9.4 years). Nineteen patients (42.2%) were aged younger than 18 years at OLT. The indications for OLT included chronic hepatic failure in 15 patients (33.3%) and fulminant (FHF) or subfulminant hepatic failure in 30 patients (66. 6%). All but 1 of the 19 pediatric patients (94.7%) were in the latter group. Twenty-five patients (55.5%) were receiving D-penicillamine, 9 patients for more than 1 year; none of the patients treated long term presented as FHF. Thirty-three patients (73.3%) survived more than 5 years after OLT. Fourteen patients (31%) died during the posttransplantation period; 7 of the 14 patients (50%) were aged younger than 18 years. Twelve patients died during the first 3 months after OLT of complications of disease and surgery, 10 of whom underwent transplantation for FHF. The other 2 patients died 6 and 9 years after transplantation of infectious problems. Eleven patients (24.4%) required retransplantation because of a primary nonfunctioning graft (n = 6), chronic rejection (n = 4), and hepatic artery thrombosis (n = 1). Seventeen patients (37.7%) presented with neurological abnormalities; 14 patients with Wilsonian neurological manifestations and 3 patients with components of increased intracranial pressure. Ten of the 13 surviving patients with hepatic insufficiency and neurological abnormalities at OLT showed significant neurological improvement. Our experience shows OLT is a life-saving procedure in patients with end-stage Wilson's disease and is associated with excellent long-term survival. The neurological manifestation of the disease can improve significantly after OLT. Earlier transplantation in patients with an unsatisfactory response to medical treatment may prevent irreversible neurological deterioration and less satisfactory improvement after OLT.",Adult;Female;Follow-Up Studies;Graft Survival;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/su [Surgery];Humans;Liver Failure/et [Etiology];Liver Transplantation/mo [Mortality];*Liver Transplantation;Male;Retrospective Studies;Time Factors;Treatment Outcome,"Eghtesad, B.;Nezakatgoo, N.;Geraci, L. C.;Jabbour, N.;Irish, W. D.;Marsh, W.;Fung, J. J.;Rakela, J.",1999,Nov,,0,0,
539,"Expression and mutagenesis of ZntA, a zinc-transporting P-type ATPase from Escherichia coli","Cation-transporting P-type ATPases comprise a major membrane protein family, the members of which are found in eukaryotes, eubacteria, and archaea. A phylogenetically old branch of the P-type ATPase family is involved in the transport of heavy-metal ions such as copper, silver, cadmium, and zinc. In humans, two homologous P-type ATPases transport copper. Mutations in the human proteins cause disorders of copper metabolism known as Wilson and Menkes diseases. E. coli possesses two genes for heavy-metal translocating P-type ATPases. We have constructed an expression system for one of them, ZntA, which encodes a 732 amino acid residue protein capable of transporting Zn(2+). A vanadate-sensitive, Zn(2+)-dependent ATPase activity is present in the membrane fraction of our expression strain. In addition to Zn(2+), the heavy-metal ions Cd(2+), Pb(2+), and Ag(+) activate the ATPase. Incubation of membranes from the expression strain with [gamma-(33)P]ATP in the presence of Zn(2+), Cd(2+), or Pb(2+) brings about phosphorylation of two membrane proteins with molecular masses of approximately 90 and 190 kDa, most likely representing the ZntA monomer and dimer, respectively. Although Cu(2+) can stimulate phosphorylation by [gamma-(33)P]ATP, it does not activate the ATPase. Cu(2+) also prevents the Zn(2+) activation of the ATPase when present in 2-fold excess over Zn(2+). Ag(+) and Cu(+) appear not to promote phosphorylation of the enzyme. To study the effects of Wilson disease mutations, we have constructed two site-directed mutants of ZntA, His475Gln and Glu470Ala, the human counterparts of which cause Wilson disease. Both mutants show a reduced metal ion stimulated ATPase activity (about 30-40% of the wild-type activity) and are phosphorylated much less efficiently by [gamma-(33)P]ATP than the wild type. In comparison to the wild type, the Glu470Ala mutant is phosphorylated more strongly by [(33)P]P(i), whereas the His475Gln mutant is phosphorylated more weakly. These results suggest that the mutation His475Gln affects the reaction with ATP and P(i) and stabilizes the enzyme in a dephosphorylated state. The Glu470Ala mutant seems to favor the E2 state. We conclude that His475 and Glu470 play important roles in the transport cycles of both the Wilson disease ATPase and ZntA.","*Adenosine Triphosphatases/bi [Biosynthesis];*Adenosine Triphosphatases/ge [Genetics];Adenosine Triphosphatases/me [Metabolism];Adenosine Triphosphate/me [Metabolism];Amino Acid Sequence;Bacterial Proteins/bi [Biosynthesis];Bacterial Proteins/ge [Genetics];Bacterial Proteins/me [Metabolism];*Carrier Proteins/bi [Biosynthesis];*Carrier Proteins/ge [Genetics];Carrier Proteins/me [Metabolism];Enzyme Activation/ge [Genetics];Escherichia coli/en [Enzymology];Escherichia coli/ge [Genetics];Hepatolenticular Degeneration/ge [Genetics];Hydrolysis;Molecular Sequence Data;*Mutagenesis, Site-Directed;Phosphates/me [Metabolism];Phosphorus Radioisotopes;Phosphorylation;*Zinc/me [Metabolism];0 (Bacterial Proteins);0 (Carrier Proteins);0 (Phosphates);0 (Phosphorus Radioisotopes);8L70Q75FXE (Adenosine Triphosphate);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-1 (Zn(II)-translocating P-type ATPase);J41CSQ7QDS (Zinc)","Okkeri, J.;Haltia, T.",1999,Oct 19,,0,0,
540,"Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p","Wilson disease (WD) and Menkes disease (MNK) are inherited disorders of copper metabolism. The genes that mutate to give rise to these disorders encode highly homologous copper transporting ATPases. We use yeast and mammalian two-hybrid systems, along with an in vitro assay to demonstrate a specific, copper-dependent interaction between the six metal-binding domains of the WD and MNK ATPases and the cytoplasmic copper chaperone HAH1. We demonstrate that several metal-binding domains interact independently or in combination with HAH1p, although notably domains five and six of WDp do not. Alteration of either the Met or Thr residue of the HAH1p MTCXXC motif has no observable effect on the copper-dependent interaction, whereas alteration of either of the two Cys residues abolishes the interaction. Mutation of any one of the HAH1p C-terminal Lys residues (Lys(56), Lys(57), or Lys(60)) to Gly does not affect the interaction, although deletion of the 15 C-terminal residues abolishes the interaction. We show that apo-HAH1p can bind in vitro to copper-loaded WDp, suggesting reversibility of copper transfer from HAH1p to WD/MNKp. The in vitro HAH1/WDp interaction is metalospecific; HAH1 preincubated with Cu(2+) or Hg(+) but not with Zn(2+), Cd(2+), Co(2+), Ni(3+), Fe(3+), or Cr(3+) interacted with WDp. Finally, we model the protein-protein interaction and present a theoretical representation of the HAH1p.Cu.WD/MNKp complex.","Adenosine Triphosphatases/ch [Chemistry];*Adenosine Triphosphatases/me [Metabolism];Amino Acid Motifs;Carrier Proteins/ch [Chemistry];*Carrier Proteins/me [Metabolism];*Cation Transport Proteins;Cell Line;Cytoplasm/me [Metabolism];Humans;Metallochaperones;Models, Molecular;*Molecular Chaperones;Protein Binding;*Recombinant Fusion Proteins;Two-Hybrid System Techniques;0 (ATOX1 protein, human);0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Metallochaperones);0 (Molecular Chaperones);0 (Recombinant Fusion Proteins);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (ATP7A protein, human);EC 3-6-3-4 (Wilson disease protein)","Larin, D.;Mekios, C.;Das, K.;Ross, B.;Yang, A. S.;Gilliam, T. C.",1999,Oct 01,,0,0,
541,Treatment of Wilson's disease with zinc,,Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Time Factors;Zinc/me [Metabolism];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Brewer, G. J.",1999,Sep,,0,0,
542,Comparative mechanism and toxicity of tetra- and dithiomolybdates in the removal of copper,"Tetrathiomolybdate (TTM) can be used as a specific chelator to remove copper (Cu) accumulating in the form bound to metallothionein (MT) in the livers of Wilson disease patients and Long-Evans rats with a cinnamon-like coat color (LEC rats). However, an adverse effect, hepatotoxicity, was observed occasionally on its clinical application. The mechanism underlying the adverse effect of TTM has been studied in comparison with dithiomolybdate (DTM), and a safer and more effective therapy by TTM was proposed based on the mechanism. The activity of glutamic-pyruvic transaminase (GPT) in serum was shown to increase significantly on the treatment of Wistar rats with sulfide produced through hydrolytic degradation of TTM and DTM, the latter being more easily degraded. The hydrolytic degradation of TTM was enhanced under acidic conditions. Cu in Cu-containing enzymes such as Cu,Zn-superoxide dismutase (SOD) in liver and ceruloplasmin (Cp) in plasma was decreased by excessive thiomolybdates, the Cu being found in the plasma in the form of a Cu/thiomolybdate/albumin complex. The decreased amounts of Cu in SOD and Cp were explained by the sequestration of Cu from their chaperones by thiomolybdates rather than the direct removal of Cu from the enzymes. Although both TTM and DTM remove Cu from MT, DTM is not appropriate as a therapeutic agent for Wilson disease due to its easy hydrolysis and production of sulfide.","Animals;Ceruloplasmin/me [Metabolism];Chelating Agents/ch [Chemistry];*Chelating Agents/tu [Therapeutic Use];Chelating Agents/to [Toxicity];Copper/bl [Blood];*Copper/ch [Chemistry];Drug Stability;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/me [Metabolism];Molybdenum/bl [Blood];Molybdenum/ch [Chemistry];Molybdenum/me [Metabolism];*Molybdenum/tu [Therapeutic Use];Molybdenum/to [Toxicity];Rats;Rats, Long-Evans;0 (Chelating Agents);16608-22-3 (dithiomolybdic acid);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-16-3-1 (Ceruloplasmin)","Ogra, Y.;Komada, Y.;Suzuki, K. T.",1999,Jun 30,,0,0,
543,Wilson's disease,"Wilson's disease is an autosomal recessive inherited disorder of copper metabolism resulting in pathological accumulation of copper in many organs and tissues. The Wilson disease gene is localized on human chromosome 13 and codes for a copper transporting P-type ATPase, -ATP7B. About one hundred mutations occurring throughout the whole gene have been documented so far. The most common is the His1069Gln point mutation. Wilson's disease may present under a variety of clinical conditions, the most common being liver disease (ranging from acute hepatitis, fulminant hepatic failure, chronic hepatitis, and cirrhosis), haemolytic anaemia, and neuropsychiatric disturbances. The diagnosis of Wilson's disease is usually made on the basis of clinical findings (Kayser-Fleischer rings, typical neurologic symptoms) and laboratory abnormalities (low serum caeruloplasmin, increased hepatic copper content). Molecular genetic testing is now the standard for testing asymptomatic siblings. Diagnosis in patients presenting with liver diseases is difficult and requires a combination of various laboratory parameters. Lifelong treatment with chelating agents (d-penicillamine, trientine) or with zinc is usually sufficient to stabilize the patient and to achieve clinical remission in most. Patients with advanced liver disease benefit from orthotopic liver transplantation. [References: 55]",DNA Mutational Analysis;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/et [Etiology];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/px [Psychology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver/me [Metabolism],"Ferenci, P.",1999,Jun-Jul,,0,0,
544,Treatment and management of Wilson's disease,"Wilson's disease is an autosomal recessive disorder related to the copper metabolism. The clinical symptoms are due to copper deposition in various tissues, including liver, brain, kidney, cornea and others. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents and a low copper diet. D-Penicillamine is considered to be the first choice as a copper-chelating agent. Patients require 15-25 mg/kg daily in the early stages of treatment and this drug should also be given more than 2 h before meals. Some undesirable or serious side-effects, such as systemic lupus erythematosus (SLE) and nephrotic syndrome, do occur in 20-25% of all patients. In such cases, trienthylene tetramine (trientine) appears to be as effective as penicillamine. This drug is usually used when D-penicillamine has to be withdrawn. It is also sometimes administered to patients with neurological symptoms as a first-choice drug. It is given in doses of 40-50 mg/kg daily, in the same manner as for D-penicillamine. Zinc salt administration has also emerged as an interesting supportive therapy for both treatments. A dose of 5-7.5 mg/kg daily is given before meals. The copper content of the diet should be less than 1 mg/day in the early stages of treatment. Thereafter, it can be increased to 1.0-1.5 mg/day during well-controlled periods. Liver transplantation is now performed in many countries for patients with either the fulminant or chronic progressive types of Wilson's disease. [References: 21]",*Chelating Agents/tu [Therapeutic Use];*Chelation Therapy;*Copper;Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/su [Surgery];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver/me [Metabolism];Liver Transplantation;*Penicillamine/tu [Therapeutic Use];Treatment Outcome;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Shimizu, N.;Yamaguchi, Y.;Aoki, T.",1999,Aug,,0,0,
545,1H NMR studies of the reactions of copper(I) and copper(II) with D-penicillamine and glutathione,"Reactions of copper ions with D-penicillamine (PSH) have been monitored by 1H NMR spectroscopy in the presence and absence of glutathione (GSH) under aerobic as well as anaerobic conditions. In D2O solution at pD = 7.4, PSH coordinates to Cu+ to form PS(-)-Cu+ under argon atmosphere as revealed from the broadening of each signal. In the presence of dioxygen, the complex was converted to the well-characterized purple cluster species consisting of Cu+, Cu2+, and PS2-. Addition of GSH into this solution quickly decomposed the cluster by the reduction of Cu2+ to Cu+. The cluster species was, however, reproduced after several hours because of the oxidation of Cu+ back to Cu2+. The solution containing both PSH and GSH formed three possible disulfides, PSSP, GSSG, and PSSG, under aerobic conditions. Addition of Cu+ to this solution again produced the purple cluster through several redox reactions. On the basis of these results, it was concluded that the co-existence of PSH and/or PSSP with Cu+ and/or Cu2+ leads to the formation of the stable cluster species regardless of the presence or absence of the other thiols such as GSH. This must be one of the reasons why PSH works in living cells as an effective drug for the Wilson disease.",Aerobiosis;Anaerobiosis;Argon;*Copper/ch [Chemistry];Disulfides/ch [Chemistry];*Glutathione/ch [Chemistry];Magnetic Resonance Spectroscopy;Oxygen/ch [Chemistry];*Penicillamine/ch [Chemistry];0 (Disulfides);67XQY1V3KH (Argon);789U1901C5 (Copper);GAN16C9B8O (Glutathione);GNN1DV99GX (Penicillamine);S88TT14065 (Oxygen),"Kato, N.;Nakamura, M.;Uchiyama, T.",1999,Jun 15,,0,0,
546,Penicillamine as a controversial treatment for Wilson's disease,,*Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"LeWitt, P. A.",1999,Jul,,0,0,
547,Penicillamine should not be used as initial therapy in Wilson's disease,,*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Copper/po [Poisoning];Disease Progression;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Brewer, G. J.",1999,Jul,,0,0,
548,Penicillamine: the treatment of first choice for patients with Wilson's disease,,Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1999,Jul,,0,0,
549,Treatment of copper associated liver disease in childhood,"BACKGROUND/AIMS: Copper associated liver disease is accompanied with high liver copper concentrations and progressive liver disease in infancy or childhood. The disease is thought to be due to excessive dietary copper overload (copper-enriched water supply) and in addition to be based on a genetic predisposition. Treatment with penicillamine in Indian childhood disease, which probable has the same etiology, is effective when it is started early enough as well as in Wilson's disease. We aimed to describe the clinical features of copper associated liver disease and report our experience with different treatment options in German children. METHODS/RESULTS: Two boys presented at the age of 6 and 10 months with abdominal distension due to hepatosplenomegaly. The diagnosis of copper associated liver disease was made based on feeding history, standard liver function parameters, liver biopsy and assessment of dry weight copper concentration and urinary excretion of copper. Both had micronodular cirrhosis, ballooning of hepatocytes and Mallory bodies. In child A improvement of liver function was observed after introduction of penicillamine therapy and copper-reduced diet. The treatment was stopped after 18 months, when normalisation of copper concentration in the liver had occured. In child B acute liver failure developed despite initiation of treatment. The boy was transplanted successfully. Both children are presently healthy 10 years after transplantation and 4 years after begin of chelating therapy, respectively. CONCLUSIONS: We conclude, that early chelating therapy with penicillamine can be successful in children with copper associated liver disease. In case of delayed diagnosis and acute liver failure liver transplantation is necessary. Our case reports highlight the urgent need of rapid diagnosis of copper associated liver disease in order to initiate early chelating therapy. Copper associated liver disease should obviously be considered in liver disease of unknown origin. Possible causes of excessive dietary copper intake should be ascertained.","Chelating Agents/tu [Therapeutic Use];*Chemical and Drug Induced Liver Injury;*Copper/to [Toxicity];Drinking;Germany;Humans;Infant;*Liver Diseases/dt [Drug Therapy];Liver Diseases/su [Surgery];Liver Failure, Acute/ci [Chemically Induced];Liver Failure, Acute/dt [Drug Therapy];Liver Failure, Acute/su [Surgery];Liver Transplantation;Male;Penicillamine/tu [Therapeutic Use];Water Pollutants, Chemical/to [Toxicity];Water Supply;0 (Chelating Agents);0 (Water Pollutants, Chemical);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Rodeck, B.;Kardoff, R.;Melter, M.",1999,Jun 28,,0,0,
550,Molybdenum,"Molybdenum does not exist naturally in the pure metallic form and of the 5 oxidation states (2-6) the predominant species are Mo(IV) and Mo(VI). Molybdenum rapidly polymerizes to a wide variety of complex polymolybdate compounds in solution. The vast majority of molybdenum is used in metallurgical applications (stainless steel, cast-iron alloys). Ammonium tetrathiomolybdate is an experimental chelating agent for Wilson's disease. For the general population, the diet is the most important source of molybdenum and concentrations in water and air usually are negligible. The average daily dietary intake is about 0.1-0.5 mg m.o. Molybdenum is an essential element with relatively low toxicity. Enzymes containing molybdenum catalyze basic metabolic reactions in the carbon, sulfur, and nitrogen cycles. Elimination of molybdenum occurs via the kidney and usually is complete within several weeks. Molybdenosis (teart) is a form of molybdenum toxicity that produces a disease in ruminants similar to copper-deficiency. Little data are available on the human toxicity of molybdenum. A gout-like syndrome and pneumoconiosis have been associated with excessive concentrations of molybdenum, but the inadequate design of the studies prevents an adequate determination of the etiology of these effects. [References: 35]",Animals;Humans;Molybdenum/ch [Chemistry];Molybdenum/pk [Pharmacokinetics];*Molybdenum/to [Toxicity];Occupational Exposure;Organometallic Compounds/ch [Chemistry];Organometallic Compounds/pk [Pharmacokinetics];Organometallic Compounds/to [Toxicity];0 (Organometallic Compounds);81AH48963U (Molybdenum),"Barceloux, D. G.",1999,,,0,0,
551,Copper,"Copper is an essential trace element, which is an important catalyst for heme synthesis and iron absorption. Following zinc and iron, copper is the third most abundant trace element in the body. Copper is a noble metal, like silver and gold. Useful industrial properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability. Most of the metallic copper appears in electrical applications. Copper is a constituent of intrauterine contraceptive devices and the release of copper is necessary for their contraceptive effects. The average daily intake of copper in the US is about 1 mg Cu with the primary source being the diet. The bioavailability of copper from the diet is about 65-70% depending on a variety of factors including chemical form, interaction with other metals, and dietary components. The biological half-life of copper from the diet is 13-33 days with bilary excretion being the major route of elimination. Copper sulfate is a gastric irritant that produces erosion of the lining of the gastrointestinal tract. Chronic copper toxicity is rare and primarily affects the liver. Wilson's disease and Indian childhood cirrhosis are examples of severe chronic liver disease that results from the genetic predisposition to the hepatic accumulation of copper. The serum copper concentration ranges up to approximately 1.5 mg/L in healthy persons. Gastrointestinal symptoms occur at whole blood concentrations near 3 mg Cu/L. Chelating agents (CaNa2EDTA, BAL) are recommended in severe poisoning, but there are little pharmacokinetic data to evaluate the effectiveness of these agents. [References: 118]",Animals;Copper/ch [Chemistry];Copper/pk [Pharmacokinetics];Copper/ph [Physiology];*Copper/to [Toxicity];Environmental Pollutants/pk [Pharmacokinetics];Environmental Pollutants/to [Toxicity];Humans;0 (Environmental Pollutants);789U1901C5 (Copper),"Barceloux, D. G.",1999,,,0,0,
552,"Metal ion transporters in mammals: structure, function and pathological implications","Despite the importance of metal ions in several catalytic functions, there has been, until recently, little molecular information available on the mechanisms whereby metal ions are actively taken up by mammalian cells. The classical concept for iron uptake into mammalian cells has been the endocytosis of transferrin-bound Fe3+ by the transferrin receptor. Studies with hypotransferrinaemic mice revealed that in the intestine mucosal transferrin is derived from the plasma and that its presence is not required in the intestinal lumen for dietary iron absorption. This suggests that, at least in the intestine, other non-receptor-mediated uptake systems exist. The molecular identification of metal ion transporters is of great importance, in particular since an increasing number of human diseases are thought to be related to disturbances in metal ion homeostasis, including metal ion overload and deficiency disorders (i.e. anaemia, haemochromatosis, Menkes disease, Wilson's disease), and neurodegenerative diseases (i.e. Alzheimer's, Friedreich's ataxia and Parkinson's diseases). Furthermore, susceptibilities to mycobacterial infections are caused by metal ion transporter defects. The pathological implications of disturbed metal ion homeostasis confirm the vital roles these metal ions play in the catalytic function of many enzymes, in gene regulation (zinc-finger proteins), and in free radical homeostasis. Recent insights have significantly advanced our knowledge of how metal ions are taken up or released by mammalian cells. The purpose of this review is to summarize these advances and to give an overview on the growing number of mammalian metal ion transporters. [References: 109]",Carrier Proteins/ch [Chemistry];*Carrier Proteins/me [Metabolism];Carrier Proteins/ph [Physiology];Homeostasis/ph [Physiology];Humans;*Metals/me [Metabolism];0 (Carrier Proteins);0 (Metals),"Rolfs, A.;Hediger, M. A.",1999,Jul 01,,0,0,
553,Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice,"We previously reported that the common toxic gain-of-function in various mutant copper-zinc superoxide dismutases (SOD1) seen in patients with familial amyotrophic lateral sclerosis (ALS) was an abnormal copper release from the enzyme protein. In this study, trientine and ascorbate, known to have a beneficial effect in an animal model of Wilson disease, were administered to transgenic mice overexpressing a mutated human SOD1 (G93A). The onset of neurological signs in the treated group was significantly delayed compared with that in the control group, and the time to reach total paralysis in the treated group was delayed as well. Since the agents used in this study cause low toxicity in animals and humans, this treatment may be a good candidate for clinical application.","*Amyotrophic Lateral Sclerosis/dt [Drug Therapy];Amyotrophic Lateral Sclerosis/en [Enzymology];Amyotrophic Lateral Sclerosis/mo [Mortality];Animals;*Ascorbic Acid/pd [Pharmacology];*Chelating Agents/pd [Pharmacology];Copper/me [Metabolism];Disease Models, Animal;Gene Expression Regulation, Enzymologic;Humans;Mice;Mice, Transgenic;Superoxide Dismutase/ge [Genetics];Superoxide Dismutase/me [Metabolism];Survival Analysis;*Trientine/pd [Pharmacology];0 (Chelating Agents);789U1901C5 (Copper);EC 1-15-1-1 (Superoxide Dismutase);PQ6CK8PD0R (Ascorbic Acid);SJ76Y07H5F (Trientine)","Nagano, S.;Ogawa, Y.;Yanagihara, T.;Sakoda, S.",1999,Apr 23,,0,0,
554,[Type-III hyperlipoproteinemia in a girl with Wilson's disease],,Biopsy;Child;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];Humans;*Hyperlipoproteinemia Type III/di [Diagnosis];Hyperlipoproteinemia Type III/dt [Drug Therapy];Hyperlipoproteinemia Type III/et [Etiology];Lipoproteins/bl [Blood];Liver/pa [Pathology];Penicillamine/ad [Administration & Dosage];0 (Lipoproteins);GNN1DV99GX (Penicillamine),"Bonet Serra, B.;Henry Knopp, R.",1999,Jan,,0,0,
555,Zinc therapy increases duodenal concentrations of metallothionein and iron in Wilson's disease patients,"OBJECTIVE: Wilson's disease is effectively treated by zinc administration which, in vitro, increases metallothionein concentrations. To ascertain whether the latter also occurs in humans we measured metallothionein and trace element concentrations in the duodenal mucosa of 15 Wilson's disease patients: 12 treated with zinc sulphate, two treated with penicillamine, and one not yet on treatment. The control group consisted of 17 patients with dyspepsia, who underwent the same study protocol. METHODS: Metallothionein and trace element concentrations were measured in duodenal mucosa biopsies according to the silver-saturation hemolysate method and atomic absorption spectrophotometry. RESULTS: Metallothionein concentrations increased by 1500% after zinc and 150% after penicillamine in Wilson's disease patients, with respect to controls who had negative endoscopy and Wilson's disease patients who were not treated. A significant correlation was found between metallothionein and duodenal zinc concentrations. Mucosal iron concentration increased in Wilson's disease patients whether they were treated with zinc or penicillamine. Duodenum with duodenitis also had significantly increased iron levels compared with normal duodenum. CONCLUSIONS: Zinc administration increases intestinal metallothionein in Wilson's disease patients. The blockade of copper absorption and its elimination in the stools on desquamation of the intestinal cells probably explains one of the mechanisms underlying the effect of zinc treatment. Despite normal endoscopy, Wilson's disease patients present increased mucosal iron concentrations similar to those in controls with duodenitis. Metallothionein may therefore prevent oxidative damage caused by metal toxicity.",Adult;Case-Control Studies;Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Duodenitis/me [Metabolism];*Duodenum/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Intestinal Mucosa/me [Metabolism];*Iron/me [Metabolism];Male;*Metallothionein/me [Metabolism];Penicillamine/tu [Therapeutic Use];*Zinc Sulfate/tu [Therapeutic Use];0 (Chelating Agents);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);9038-94-2 (Metallothionein);E1UOL152H7 (Iron);GNN1DV99GX (Penicillamine),"Sturniolo, G. C.;Mestriner, C.;Irato, P.;Albergoni, V.;Longo, G.;D'Inca, R.",1999,Feb,https://dx.doi.org/10.1111/j.1572-0241.1999.851_w.x,0,0,
556,Zinc therapy induction of intestinal metallothionein in Wilson's disease,,"*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;*Intestine, Small/me [Metabolism];*Metallothionein/me [Metabolism];*Zinc/tu [Therapeutic Use];9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc)","Brewer, G. J.",1999,Feb,https://dx.doi.org/10.1111/j.1572-0241.1999.00301.x,0,0,
557,A high index of suspicion: the key to an early diagnosis of Wilson's disease in childhood,"BACKGROUND: To study the clinical features of Wilson's disease in childhood. METHODS: Retrospective review of the clinical, laboratory, and histologic features and prognosis of Wilson's disease in 26 Spanish children. RESULTS: The first medical visit, at age 9.8+/-3.4 years (range, 4-16 years), was prompted by liver dysfunction detected accidentally (61%), symptoms of liver disease (27%), family screening (8%), and extrapyramidal symptoms and personality changes (4%). There were laboratory data of hepatic failure in 27%. All copper metabolism test results (total serum copper, 24-hour urine excretion, serum ceruloplasmin) were abnormal in 62%, two in 27%, and one in 11%. All patients in whom extrahepatic involvement was found at diagnosis had severe liver disease. Histologic findings were portal fibrosis with steatosis (29%), cirrhosis (21%), portal fibrosis (17%), chronic active hepatitis (17%), and minimal changes or normality (17%). Penicillamine was administered to all but one patient. Four children underwent liver transplantation, three of them having received penicillamine for 12, 45, and 70 days. Three other patients recovered from liver failure after 1 year of treatment with penicillamine. After a follow-up of 4.5+/-3.3 years, all the children survived. Penicillamine caused severe toxicity in one patient. CONCLUSIONS: Wilson's disease in childhood is generally detected by maintaining a high suspicion of liver disease in patients who have no or nonspecific hepatic symptoms. Kayser-Fleischer ring is rare in childhood. Drug therapy is effective and well tolerated, even in some cases of hepatic insufficiency.","Adolescent;Ceruloplasmin/an [Analysis];Chelating Agents;Child;Child, Preschool;Copper/bl [Blood];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Liver/pa [Pathology];Liver/pp [Physiopathology];Liver Diseases/di [Diagnosis];Liver Diseases/pa [Pathology];Liver Diseases/pp [Physiopathology];Liver Function Tests;Liver Transplantation;Male;Penicillamine/tu [Therapeutic Use];Prognosis;Retrospective Studies;Spain;0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Sanchez-Albisua, I.;Garde, T.;Hierro, L.;Camarena, C.;Frauca, E.;de la Vega, A.;Diaz, M. C.;Larrauri, J.;Jara, P.",1999,Feb,,0,0,
558,Wilson's disease,"Wilson's disease is an autosomal, recessive-inherited disorder of impaired biliary copper excretion that results in the accumulation of copper in various organs including the liver, the cornea and the brain. The Wilson's disease gene on chromosome 13 codes for a copper transporting P-type ATPase-ATP7B. More than 60 mutations of this gene have been described. The diagnosis of Wilson's disease is based on clinical findings and laboratory abnormalities and can be made if two of the following symptoms are present: Kayser-Fleischer rings; topical neurologic symptoms; and low serum ceruloplasmin levels. In less typical cases diagnosis requires various other tests of copper metabolism. Effective medical treatment with copper chelators (D-penicillamine, trientine) or zinc results in symptomatic improvement and normal life expectancy. Orthotopic liver transplantation is indicated in advanced cases with hepatic decompensation or in patients with fulminant Wilson's disease. [References: 57]",Copper/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver/me [Metabolism];Liver Transplantation;Mutation;Penicillamine/tu [Therapeutic Use];Prognosis;Zinc/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Ferenci, P.",1998,Feb,,0,0,543
559,Wilson's disease with concomitant beta thalassaemia and factor V deficiency,"A case of late presentation of Wilson's disease in a female with a thalassaemic trait is reported in whom diagnosis of Factor V deficiency was made. Despite ignoring the disease for years the patient had compensated cirrhosis. She had a dramatic family history of Wilson's disease affecting at least two brothers and two sisters. Moreover, her haematologic problems were not clinically revealed until diagnosis had been made on the basis of suspicions arising from laboratory results. The therapy of choice for hepatolenticular degeneration was not feasible due to the patient's refusal. Zinc salts were, therefore, administered. To our knowledge the association of such rare genetic disorders has not been reported.",*Factor V Deficiency/co [Complications];Factor V Deficiency/ge [Genetics];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Middle Aged;Pedigree;Zinc/tu [Therapeutic Use];*beta-Thalassemia/co [Complications];beta-Thalassemia/ge [Genetics];J41CSQ7QDS (Zinc),"Giannini, E.;Fasoli, A.;Botta, F.;Testa, R.",1998,Dec,,0,0,
560,Wilson disease,"Wilson disease is a recessively inherited disorder of copper transport. Clinical features are highly variable, with any combination of neurological, hepatic or psychiatric illness. The age of onset varies from 3 to 50 years of age. Diagnosis is challenging because no specific combination of clinical or biochemical features is necessarily definitive. The genetic defect is due to a variety of abnormalities in a copper-transporting membrane ATPase. Most of the more than 80 mutations are present at a low frequency, and mutations differ between ethnic groups. At least two mutations are sufficiently common to aid in rapid diagnosis, in European and Asian populations respectively. Molecular analysis can provide a definitive diagnosis for asymptomatic sibs. Treatment, using chelating agents or zinc, is most effective when started before permanent tissue damage occurs. [References: 91]","Adolescent;Adult;Child;Child, Preschool;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration;Humans;Middle Aged;Mutation","Roberts, E. A.;Cox, D. W.",1998,Jun,,0,0,
561,Early onset of nephrotic syndrome after treatment with D-penicillamine in a patient with Wilson's disease,Wilson's disease responds to a variety of treatments including D-penicillamine and trientene. Nephrotic syndrome is a late complication of D-penicillamine treatment. We report a pediatric patient with Wilson's disease who developed nephrotic syndrome 2 wk after beginning D-penicillamine. His nephrosis resolved and his disease is quiescent with trientene treatment.,*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];Child;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Nephrotic Syndrome/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Retreatment;Time Factors;Trientine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Siafakas, C. G.;Jonas, M. M.;Alexander, S.;Herrin, J.;Furuta, G. T.",1998,Dec,https://dx.doi.org/10.1111/j.1572-0241.1998.00715.x,0,0,
562,D-penicillamine-induced pancreatic islet autoantibody production is independent of the immunogenetic background: a lesson from patients with Wilson's disease,"D-penicillamine (d-PA) was reported to induce various immunological abnormalities including production of autoantibodies to insulin. These abnormalities were mainly described in patients with primary immunological disorders such as rheumatoid arthritis. In order to clarify whether d-PA-induced immune disorders are restricted to patients genetically prone to develop autoimmune diseases or to a direct drug effect, we tested for the presence of various autoantibodies and for molecular HLA typing in 17 patients with Wilson's disease treated with this drug. In 2/17 patients, low-titer (10 JDFU) circulating islet cell autoantibodies (ICA) were detected, while another patient was positive for the presence of insulin autoantibodies. None of the sera tested showed reactivity for glutamic acid decarboxylase or ICA512. Five of twelve patients were positive for anti-single-stranded DNA autoantibody. Molecular HLA typing of the autoantibody-positive subjects showed that they carry HLA haplotypes not associated with insulin-dependent diabetes. The insulin response to intravenous glucose tolerance test in two patients with autoantibodies was found to be normal. A second blood testing of the autoantibody-positive patients 5 months following initial evaluation revealed conversion to negativity in all three. Our results suggest that d-PA-induced autoantibodies in patients with Wilson's disease are independent of the immunogenetic background characteristics of diabetes. Copyright 1998 Academic Press.","Adolescent;Adult;*Autoantibodies/bi [Biosynthesis];Child;Diabetes Mellitus, Type 1/ge [Genetics];Diabetes Mellitus, Type 1/im [Immunology];Female;HLA Antigens/ge [Genetics];Haplotypes;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/im [Immunology];Humans;Immunogenetics;*Islets of Langerhans/im [Immunology];Male;*Penicillamine/ae [Adverse Effects];0 (Autoantibodies);0 (HLA Antigens);0 (islet cell antibody);GNN1DV99GX (Penicillamine)","Kauschansky, A.;Frydman, M.;Assa, S.;Kwon, O. J.;Israel, S.;Lazard, D.;Sprecher, E.;Bloch, K.;Brautbar, C.;Vardi, P.",1998,Dec,,0,0,
563,Treatment of Wilson's disease with zinc: XV long-term follow-up studies,"Wilson's disease is an inherited disease of copper accumulation caused by a failure of biliary excretion of excess copper. Accumulated copper causes liver disease in these patients, and in perhaps two thirds of patients, it causes brain damage leading to clinical neurologic or psychiatric dysfunction. Maintenance treatment involves reversing the positive copper balance. The earliest approaches have used chelators, such as penicillamine or trientine, which increase the urinary excretion of copper. A more recent approach has used zinc, which blocks the absorption of copper and increases copper excretion in the stool. Because of the high level of endogenously secreted copper in alimentary secretions, the reabsorption of which is partially blocked by zinc therapy, zinc acts to remove accumulated copper from the body as well as prevent its reaccumulation. In the present article we present data on the long-term follow-up (up to 10 years) of maintenance zinc treatment of 141 patients with Wilson's disease. The data presented document that zinc is effective as a sole therapy in the long-term maintenance treatment of Wilson's disease and that it has a low toxicity. The results demonstrate the efficacy of zinc therapy in treating the presymptomatic patient from the beginning of therapy. We also present limited data on the use of zinc in the treatment of pregnant patients and children who have Wilson's disease; these data also indicate efficacy and low toxicity. The median follow-up period for the group as a whole is 4.8 years; for the presymptomatic patients it is 6.5 years; for the children it is 3.6 years.","Adolescent;Adult;Brain/pa [Pathology];Ceruloplasmin/an [Analysis];Child;Child, Preschool;Copper/me [Metabolism];Copper/pd [Pharmacology];Copper Radioisotopes;Female;Follow-Up Studies;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Liver/me [Metabolism];Liver Function Tests;Magnetic Resonance Imaging;Male;Nervous System Diseases/dt [Drug Therapy];Nervous System Diseases/pp [Physiopathology];Neurologic Examination;Pregnancy;Speech Production Measurement;Treatment Outcome;Zinc Acetate/bl [Blood];*Zinc Acetate/tu [Therapeutic Use];Zinc Acetate/ur [Urine];0 (Copper Radioisotopes);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);FM5526K07A (Zinc Acetate)","Brewer, G. J.;Dick, R. D.;Johnson, V. D.;Brunberg, J. A.;Kluin, K. J.;Fink, J. K.",1998,Oct,,0,0,
564,Zinc treatment of Wilson's disease,,Drug Approval;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;United States;United States Food and Drug Administration;*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc),"Hoogenraad, T. U.",1998,Oct,,0,0,
565,Wilson's disease before and after 5 years of treatment with D-penicillamine,,Adult;*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];Radiography;GNN1DV99GX (Penicillamine),"Zachoval, R.;Glaser, C.",1998,Sep,,0,0,
566,Five successful deliveries following 9 consecutive spontaneous abortions in a patient with Wilson disease,,"Abortion, Habitual/co [Complications];*Abortion, Habitual;Adult;Ceruloplasmin/an [Analysis];Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Copper/ur [Urine];Delivery, Obstetric;Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Humans;Penicillamine/tu [Therapeutic Use];Pregnancy;Pregnancy Complications/dt [Drug Therapy];*Pregnancy Complications;*Pregnancy Outcome;0 (Chelating Agents);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Mustafa, M. S.;Shamina, A. H.",1998,Aug,,0,0,
567,Cerebral manifestation of Wilson's disease successfully treated with liver transplantation,"The main indication for orthotopic liver transplantation (OLTx) in Wilson's disease (WD) is severe hepatic decompensation. Our 15-year-old patient is the second case to date in whom OLTx was performed because of neurologic manifestations resulting from WD. His initial condition involving recurrent headaches, tremor, and athetoid hand movements progressively deteriorated during therapy with D-penicillamine, zinc sulfate, and trientine until he was severely dysarthric, unable to walk, and bedridden. After OLTx, his neurologic condition became almost normal.",Adolescent;Brain Diseases/co [Complications];*Brain Diseases/th [Therapy];Copper/me [Metabolism];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/th [Therapy];Humans;*Liver Transplantation;Male;789U1901C5 (Copper),"Bax, R. T.;Hassler, A.;Luck, W.;Hefter, H.;Krageloh-Mann, I.;Neuhaus, P.;Emmrich, P.",1998,Sep,,0,0,
568,Effect of treatment of Wilson's disease on natural history of haemochromatosis,,Adult;*Chelating Agents/tu [Therapeutic Use];*Hemochromatosis/co [Complications];Hemochromatosis/pa [Pathology];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Homozygote;Humans;Liver/pa [Pathology];Male;*Trientine/tu [Therapeutic Use];0 (Chelating Agents);SJ76Y07H5F (Trientine),"Walshe, J. M.;Cox, D. W.",1998,Jul 11,https://dx.doi.org/10.1016/S0140-6736(98)85017-4,0,0,
569,Cytopenias secondary to copper depletion complicating ammonium tetrathiomolybdate therapy for Wilson's disease,,Adult;*Chelation Therapy/ae [Adverse Effects];*Copper;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Molybdenum/tu [Therapeutic Use];*Neutropenia/ci [Chemically Induced];*Thrombocytopenia/ci [Chemically Induced];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Karunajeewa, H.;Wall, A.;Metz, J.;Grigg, A.",1998,Apr,,0,0,
570,Wilson disease and canine copper toxicosis,"In this article we review the current clinical and research status of Wilson disease and canine copper toxicosis. One of the main clinical challenges in Wilson disease is for clinicians to recognize the possibility of Wilson disease when young patients present with liver disease, psychiatric disease, or a movement-disorder type of neurologic disease. Once the possibility of the disease is recognized, many copper-related tests are available that are quite accurate in making the diagnosis or ruling it out. It is important to remember that this is an inherited disease and that family members at risk should be screened, particularly siblings. The cloning of the Wilson disease gene opened up the possibility that a direct DNA test could be developed, allowing convenient screening of certain patients and family members. However, the large number of mutations already found, with no small set of mutations dominating the picture, have thwarted this approach. Once the diagnosis has been made, a variety of treatments are available. For maintenance therapy, therapy of presymptomatic patients, and therapy of pregnant patients, we use zinc. For initial therapy of patients with liver disease, we use a combination of zinc and trientine. For initial therapy of patients with neurologic disease we use tetrathiomolybdate. Canine copper toxicosis in Bedlington terriers is due to a gene different from the gene for Wilson disease. However, the disease is treatable with the same array of anticopper therapies that work in humans. Recently, we established linkage of the copper toxicosis gene to a microsatellite marker, which has made available a linkage test to breeders of Bedlington terriers. [References: 36]",Animals;Copper/to [Toxicity];*Copper/ur [Urine];Dog Diseases/ge [Genetics];Dogs;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;Pregnancy;789U1901C5 (Copper),"Brewer, G. J.",1998,May,,0,0,
571,Severely decompensated abdominal Wilson disease treated with peritoneal dialysis: a case report,"A 12-year-old girl with severely decompensated abdominal Wilson disease was treated with abdominal dialysis in order to accelerate the excretion of chelated copper. Dialysate without human serum albumin or D-penicillamine was used and was able to accelerate the excretion of chelated copper, with an increment of 5.5-19.7% compared with urinary excretion only.",Child;Copper/bl [Blood];Fatal Outcome;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/th [Therapy];Humans;Liver Function Tests;*Peritoneal Dialysis;789U1901C5 (Copper),"Kuno, T.;Hitomi, T.;Zaitu, M.;Sato, T.;Yoshida, N.;Miyazaki, S.",1998,Feb,,0,0,
572,Prenatal exposure to penicillamine and oral clefts: case report,,"Adult;*Chelating Agents/ae [Adverse Effects];Chelating Agents/tu [Therapeutic Use];*Cleft Lip/ci [Chemically Induced];*Cleft Palate/ci [Chemically Induced];Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Pregnancy;Pregnancy Complications;*Prenatal Exposure Delayed Effects;0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Martinez-Frias, M. L.;Rodriguez-Pinilla, E.;Bermejo, E.;Blanco, M.",1998,Mar 19,,0,0,
573,Acute dystonia with thalamic and brainstem lesions after initial penicillamine treatment in Wilson's disease,"Dystonia is a common manifestation in Wilson's disease (WD). The striatum, especially the putamen, has been considered to be responsible for dystonia. We reported 3 patients who developed acute generalized dystonia and akinetic rigid syndrome following an initial therapy with d-penicillamine 125-500 mg daily. Brain MRI revealed lesions in the thalamus and the brainstem, particularly the tegmentum, and the basis pontis in addition to the basal ganglion lesions. After the episode, 1 patient continued to receive d-penicillamine therapy and 2 changed to zinc sulfate treatment. The generalized dystonia improved in the following 3 months and 3 years respectively in 2 patients. Follow-up brain MRI of these 2 patients revealed that the lesions in the thalamus and brainstem disappeared or resolved almost completely. From these data, acute generalized dystonia with brainstem and thalamic lesions may occur in WD patients after an initial d-penicillamine therapy. Furthermore, the dystonia may resolve following the disappearance of the brainstem and thalamic lesions.",Adolescent;Adult;*Brain Stem/de [Drug Effects];Brain Stem/pa [Pathology];*Dystonia/ci [Chemically Induced];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Male;*Penicillamine/ae [Adverse Effects];*Thalamic Diseases/ci [Chemically Induced];GNN1DV99GX (Penicillamine),"Huang, C. C.;Chu, N. S.",1998,,,0,0,
574,Pretreatment and posttreatment positron emission tomographic scan imaging in a 20-year-old patient with Wilson's disease,"Wilson's disease is an autosomal-recessive inherited disorder that results in predominantly hepatic and neurologic manifestations. Neurologic abnormalities include tremor, ataxia, bradykinesia, rigidity, chorea, and dystonia. We report the clinical, radiologic, and serial FDG PET findings in a 20-year-old woman who presented with an asymmetric upper limb tremor caused by Wilson's disease. Reduced striatal and cerebral cortical glucose metabolism was demonstrated on a FDG PET study performed before the commencement of D-penicillamine therapy. After 6 months of treatment, the patient had shown only minimal clinical improvement, despite an increase in striatal and cerebral cortical glucose metabolism on a repeat FDG PET study. After 14 months of treatment, however, a moderate clinical improvement was noted and there was further increase in glucose metabolism on FDG PET.","Adult;Aged;Case-Control Studies;Cerebral Cortex/dg [Diagnostic Imaging];Cerebral Cortex/de [Drug Effects];*Cerebral Cortex/me [Metabolism];*Chelating Agents/tu [Therapeutic Use];Corpus Striatum/dg [Diagnostic Imaging];Corpus Striatum/de [Drug Effects];*Corpus Striatum/me [Metabolism];Female;Glucose/me [Metabolism];Hepatolenticular Degeneration/dg [Diagnostic Imaging];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Longitudinal Studies;Male;Middle Aged;*Penicillamine/tu [Therapeutic Use];*Tomography, Emission-Computed;0 (Chelating Agents);GNN1DV99GX (Penicillamine);IY9XDZ35W2 (Glucose)","Cordato, D. J.;Fulham, M. J.;Yiannikas, C.",1998,Jan,https://dx.doi.org/10.1002/mds.870130131,0,0,
575,Unusual liver MR findings of Wilson's disease in an asymptomatic 2-year-old girl,"We describe the unusual magnetic resonance (MR) findings of a case of Wilson's disease (WD) in an asymptomatic 2-year-old girl. Preenhanced computed tomography revealed multiple hyperdense areas in the liver. These lesions were hyperintense on T1-weighted and hypointense on T2-weighted MR images, results that might be ascribed to the paramagnetism of copper deposited in liver at a relatively early stage of the disease before severe liver cirrhosis had evolved.","Biopsy;Chelating Agents/ad [Administration & Dosage];Chelating Agents/tu [Therapeutic Use];Child, Preschool;Copper/me [Metabolism];Disease Progression;Dose-Response Relationship, Drug;Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Image Enhancement;Liver/dg [Diagnostic Imaging];Liver/me [Metabolism];*Liver/pa [Pathology];*Magnetic Resonance Imaging;Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Ko, S.;Lee, T.;Ng, S.;Lin, J.;Cheng, Y.",1998,Jan-Feb,,0,0,
576,Syndromic variability of Wilson's disease in children. Clinical study of 44 cases,"BACKGROUND: In children with Wilson's disease, no clinical or laboratory data are specific for diagnosis as in adult age. AIM: Clinical aspects and parameters of copper metabolism in a large series of pediatric cases are evaluated to establish certain criteria for diagnosis and for correct treatment, even in difficult cases. METHODS: In 44 children with Wilson's disease, clinical aspects, histological features, laboratory parameters and data of copper metabolism have been studied. Forty patients, treated with penicillamine, were followed up (median 77 months). RESULTS: The 44 cases were classified as: asymptomatic forms (nine cases, six of them siblings of affected subjects), chronic hepatitis (23 cases), hepatocerebral manifestations (four cases), decompensated cirrhosis (six cases), fulminant hepatic failure with hemolytic anemia (two cases). Ceruloplasmin levels were abnormal in 37 out of 43 tested cases, but normal in six (14%) who showed high basal and after penicillamine load urine copper excretion and increased hepatic copper content. Urine copper concentration was pathological in 35 out of 42 tested cases (83%), but normal in seven patients under six years. Hepatic copper levels were very high in all the 20 tested patients. Under treatment, 27 children had favourable outcome. One patient showed no evolution of disease, seven patients worsened because of non-compliance to the therapy (one underwent successful liver transplantation) or severe side effects. Five patients with failure died. CONCLUSIONS: Wilson's disease in children may present with a broad clinical spectrum, but the liver involvement is by far the most prevalent. The early diagnosis, based on clinical suspicion and results of copper metabolism investigation (including hepatic copper content evaluation in difficult cases) and appropriate treatment can prevent the progression of the disease.","Adolescent;Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Giacchino, R.;Marazzi, M. G.;Barabino, A.;Fasce, L.;Ciravegna, B.;Famularo, L.;Boni, L.;Callea, F.",1997,Apr,,0,0,
577,Clinical curative effects of dimercaptosuccinic acid on hepatolenticular degeneration and the impact of DMSA on biliary trace elements,"OBJECTIVE: To observe the biliary copper content of nonhepatolenticular degeneration (HLD) controls and changes in the trace elements in the bile, cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients before and after dimercaptosuccinic acid (DMSA) treatment in order to further explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA on HLD patients. METHODS: A consecutive series of 20 patients with HLD were given DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day. Their bile, cerebrospinal fluid, blood and urine samples were obtained before and after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary samples of 22 non-HLD controls were taken by drainage tube after surgical operation. Hitachi-208 atom absorption spectrophotometer was used to assay the content of copper, zinc and iron of each sample. RESULTS: DMSA could effectively improve the symptoms such as dysphasia, salivation, dysphagia and darkening of the skin; limb trembling and myotonia came second; but it showed no obvious effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It was effective for the patients who were younger and had no obvious hepatic damage. No serious side effects were seen through the course of treatment. Laboratory study showed that biliary copper content of HLD patients was evidently lower than that of non-HLD controls (P < 0.01); DMSA could evidently improve biliary copper excretion besides clearly increase urinary copper excretion (P < 0.01) and had nothing to do with biliary zinc excretion (P > 0.05). CONCLUSIONS: Biliary copper excretion disturbance participates directly in the pathophysiology of copper retention of HLD patients. DMSA is a favorable cupruretic drug for patients with HLD.",Adolescent;Adult;*Antidotes/tu [Therapeutic Use];*Bile/me [Metabolism];Child;*Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Iron/me [Metabolism];Male;*Succimer/tu [Therapeutic Use];Trace Elements/me [Metabolism];Zinc/me [Metabolism];0 (Antidotes);0 (Trace Elements);789U1901C5 (Copper);DX1U2629QE (Succimer);E1UOL152H7 (Iron);J41CSQ7QDS (Zinc),"Ren, M.;Yang, R.",1997,Sep,,0,0,
578,"Expression, purification, and metal binding properties of the N-terminal domain from the wilson disease putative copper-transporting ATPase (ATP7B)","The putative copper binding domain from the copper-transporting ATPase implicated in Wilson disease (ATP7B) has been expressed and purified as a fusion to glutathione S-transferase. Immobilized metal ion affinity chromatography revealed that the fusion protein is able to bind to columns charged with different transition metals with varying affinities as follows: Cu(II)>>Zn(II)>Ni(II)>Co(II). The fusion protein did not bind to columns charged with Fe(II) or Fe(III). 65Zinc(II) blotting analysis showed that the domain is able to bind Zn(II) over a range of pH values from 6.5 to 9.0. Competition 65Zn(II) blotting showed that Cd(II), Hg(II), Au(III), and Fe(III) can successfully compete with Zn(II), at comparable concentrations, for binding to the domain. In contrast, the domain had little or no affinity for Ca(II), Mg(II), Mn(II), and Ni(II) relative to copper. Neutron activation analysis of the copper bound to the domain showed a copper:protein ratio of 6.5-7.3:1. Both Cu(II) and Cu(I) were found to have a higher affinity for the domain relative to Zn(II). In addition, a sharp, reproducible transition was only observed in competition experiments with copper, which may suggest that copper binding has some degree of cooperativity.","*Adenosine Triphosphatases/ip [Isolation & Purification];*Adenosine Triphosphatases/me [Metabolism];Binding, Competitive;*Carrier Proteins/ip [Isolation & Purification];*Carrier Proteins/me [Metabolism];*Cation Transport Proteins;Cobalt/me [Metabolism];Copper/me [Metabolism];Escherichia coli;*Hepatolenticular Degeneration/en [Enzymology];Humans;Hydrogen-Ion Concentration;In Vitro Techniques;*Metals, Heavy/me [Metabolism];Nickel/me [Metabolism];Zinc/me [Metabolism];0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Metals, Heavy);3G0H8C9362 (Cobalt);789U1901C5 (Copper);7OV03QG267 (Nickel);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);J41CSQ7QDS (Zinc)","DiDonato, M.;Narindrasorasak, S.;Forbes, J. R.;Cox, D. W.;Sarkar, B.",1997,Dec 26,,0,0,
579,Penicillamine-related neurologic syndrome in a child affected by Wilson disease with hepatic presentation,"OBJECTIVES: To describe a case of penicillamine-related neurologic symptoms in a 9-year-old boy affected by asymptomatic Wilson disease with hepatic presentation; to compare this case with similar cases in adults; and to discuss the role of zinc therapy as an alternative treatment for patients who have an adverse reaction to penicillamine therapy. SETTING: Referral hospital. MAIN OUTCOME MEASURE: The occurrence of a neurologic syndrome that severely impaired a child's usual daily activities and his health-related quality of life after the institution of penicillamine therapy. RESULTS: Initial penicillamine therapy was chronologically related to the development of progressive neurologic deterioration in the absence of other causes of neurologic syndrome. The discontinuation of penicillamine therapy and the initiation of zinc therapy were followed by a prompt disappearance of neurologic symptoms and a return to neurologic baseline status. CONCLUSIONS: Penicillamine therapy, even in children affected by Wilson disease with hepatic presentation alone and without neurologic disease at the beginning of treatment, may trigger neurologic symptoms. Zinc therapy may be a satisfactory alternative.",Child;*Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Diseases/et [Etiology];Male;*Nervous System Diseases/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Retreatment;Syndrome;Zinc/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Porzio, S.;Iorio, R.;Vajro, P.;Pensati, P.;Vegnente, A.",1997,Sep,,0,0,
580,Metabolism of administered triethylene tetramine dihydrochloride in humans,"Triethylene tetramine dihydrochloride (trien 2HCl) has been used for the treatment of Wilson's disease, which is characterized by the accumulation of copper in various organs. We previously developed an HPLC system for analyzing trien, and found a trien metabolite in the urine when trien was orally given to humans. In this study, the metabolite was identified as 1-N-acetyltriethylene tetramine (acetyltrien) by FAB-MS and 1H-NMR spectroscopy. Trien and acetyltrien were capable of combining with copper, iron and zinc. However, the chelating activity of acetyltrien was significantly lower than that of trien. When trien was given to healthy adults, the amount of trien excreted in the urine was about 1% of the administered trien, whereas that of acetyltrien was about 8%. Most of the trien was excreted within the first 6 hours after the administration, while acetyltrien was excreted for over 26 hours. The urinary copper, iron and zinc levels all increased in parallel with the trien excretion.","Administration, Oral;Adult;*Chelating Agents/me [Metabolism];Chelating Agents/pd [Pharmacology];Chromatography, High Pressure Liquid;Copper/me [Metabolism];Copper/ur [Urine];Female;Humans;Iron/me [Metabolism];Iron/ur [Urine];Magnetic Resonance Spectroscopy;Male;Spectrometry, Mass, Fast Atom Bombardment;Trientine/aa [Analogs & Derivatives];*Trientine/me [Metabolism];Trientine/pd [Pharmacology];Trientine/ur [Urine];Zinc/me [Metabolism];Zinc/ur [Urine];0 (Chelating Agents);789U1901C5 (Copper);E1UOL152H7 (Iron);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Kodama, H.;Murata, Y.;Iitsuka, T.;Abe, T.",1997,,,0,0,
581,Penicillamine-induced degenerative dermatoses: report of a case and brief review of such dermatoses,"We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with overhealed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses. [References: 37]","Adult;*Chelating Agents/ae [Adverse Effects];Collagen/ul [Ultrastructure];*Drug Eruptions/et [Etiology];Drug Eruptions/pa [Pathology];Elastic Tissue/de [Drug Effects];Elastic Tissue/pa [Pathology];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Microscopy, Electron;*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);9007-34-5 (Collagen);GNN1DV99GX (Penicillamine)","Iozumi, K.;Nakagawa, H.;Tamaki, K.",1997,Jul,,0,0,
582,Stereotypies in Wilson's disease,,Adult;Basal Ganglia/pa [Pathology];*Chelating Agents/tu [Therapeutic Use];Female;Foot;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Magnetic Resonance Imaging;Movement Disorders/dt [Drug Therapy];*Movement Disorders/et [Etiology];Movement Disorders/pa [Pathology];Movement Disorders/pp [Physiopathology];*Penicillamine/tu [Therapeutic Use];Stereotyped Behavior/de [Drug Effects];*Stereotyped Behavior;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Yorio, A. A.;Mesri, J. C.;Pagano, M. A.;Lera, G.",1997,Jul,https://dx.doi.org/10.1002/mds.870120427,0,0,
583,Fulminant hepatic failure as the first manifestation of Wilson disease: a report of two cases,"Two cases of fulminant hepatic failure as a first manifestation of Wilson disease are reported. They were diagnosed as acute hemolytic anemia initially, and took a fatal course despite intensive medical therapy. The main object of this report is to emphasize that Wilson disease must be included in the differential diagnosis of fulminant hepatic failure in children. Liver transplantation is the only effective means of treatment in patients presenting with fulminant hepatic failure, but this procedure is difficult to perform because of insufficient organ donation in Taiwan. The best treatment for Wilson disease is prevention through diagnosis at a presymptomatic stage, and institution of life-long therapy with D. penicillamine.",Adolescent;Child;Female;*Hepatic Encephalopathy/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Humans,"Chung, C. C.;Wu, T. C.;Sun, C. H.;Chung, W. W.",1997,May,,0,0,
584,Acanthosis nigricans associated with hepatolenticular degeneration,"Acanthosis nigricans and hepatolenticular degeneration (Wilson's disease) developed simultaneously in a 16-year-old boy. The diagnosis of Wilson's disease was based on the clinical presentation, including Kayser-Fleischer ring, hypoceruloplasminemia, hypocupremia, and hypercupriuria. His skin lesions were characterized by thick, dark brown, verrucous plaques on the dorsa of both feet, the neck, axillae, and groin. The histological findings were compatible with acanthosis nigricans. Six months after treatment with D-penicillamine, two grams per day, his skin lesions and neurological symptoms were much improved and no complications were observed.",*Acanthosis Nigricans/co [Complications];Acanthosis Nigricans/pa [Pathology];Adolescent;*Hepatolenticular Degeneration/co [Complications];Humans;Male;Skin/pa [Pathology],"Thaipisuttikul, Y.",1997,Jun,,0,0,
585,Proteinuria and other renal functions in Wilson's disease,"Renal lesions have repeatedly been described in Wilson's disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-beta-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6-37 (mean 17) years who had been treated for a period of 0-15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of beta 2-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD.","Acetylglucosamine/bl [Blood];Adolescent;Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Female;Glomerular Filtration Rate;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Infant;*Kidney/pp [Physiopathology];Kidney Glomerulus/pp [Physiopathology];Kidney Tubules/pp [Physiopathology];Male;Molecular Weight;Penicillamine/tu [Therapeutic Use];*Proteinuria/et [Etiology];Proteinuria/pp [Physiopathology];0 (Chelating Agents);GNN1DV99GX (Penicillamine);V956696549 (Acetylglucosamine)","Sozeri, E.;Feist, D.;Ruder, H.;Scharer, K.",1997,Jun,,0,0,
586,Liver transplantation: treatment of choice for hepatic and neurological manifestation of Wilson's disease,"Liver transplantation (LTX) is an approved method to treat patients with end-stage liver cirrhosis and acute liver failure due to Wilson's disease. Initially, there was some consideration about the indication for LTX in the case of Wilson's disease with severe neurological impairment but normal liver function. From 1988 until 1995, 13 out of 700 LTX (1.9%) were performed for Wilson's disease. Indications for LTX were (I) intractable neurological impairment with normal liver function (n = 4; including one patient with Child A cirrhosis), (II) fulminant hepatic failure (n = 3), and (III) end-stage liver cirrhosis (n = 6) (Child B, n = 1; Child C, n = 5). There were 8 females and 5 males with a mean age of 27 yr (range 15-34 yr). All patients of group I required continuous nursing care before LTX, in spite of pretreatment with d-penicillamine and zinc. The most frequent symptoms in these patients were dysphagia (n = 4), dysarthria (n = 4), tremor (n = 4), sialorrhea (n = 3), ataxia (n = 3), dystonia (n = 3) and handwriting difficulties (n = 3). All patients of group II presented with hemolytic anemia. The survival rate was 100%, and all patients were doing well after a mean follow-up period of 32.8 months (range 8-68 months). The postoperative course was without severe infectious and other complications. All patients of group I revealed the first signs of improvement for all types of neurological symptoms 4-6 wk after LTX. One patient has been without any symptoms from 18 months until 5.5 yr after LTX. Two patients with short-term follow-up also had noticeable improvement of neurological impairment, but residual symptoms are still present. One patient showed only slight improvement. We conclude that Wilson's disease may be a good indication for LTX for both neurological manifestation with stable liver function and hepatic manifestation with cirrhosis or acute liver failure.","Adolescent;Adult;Anemia, Hemolytic/pp [Physiopathology];Ataxia/pp [Physiopathology];Chelating Agents/tu [Therapeutic Use];Deglutition Disorders/pp [Physiopathology];Dysarthria/pp [Physiopathology];Dystonia/pp [Physiopathology];Female;Follow-Up Studies;Handwriting;Hepatic Encephalopathy/su [Surgery];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/nu [Nursing];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration/su [Surgery];Humans;Liver Cirrhosis/pp [Physiopathology];*Liver Cirrhosis/su [Surgery];Liver Failure, Acute/pp [Physiopathology];*Liver Failure, Acute/su [Surgery];*Liver Transplantation;Male;Movement Disorders/pp [Physiopathology];*Movement Disorders/su [Surgery];Penicillamine/tu [Therapeutic Use];Sialorrhea/pp [Physiopathology];Survival Rate;Treatment Outcome;Tremor/pp [Physiopathology];Zinc/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Schumacher, G.;Platz, K. P.;Mueller, A. R.;Neuhaus, R.;Steinmuller, T.;Bechstein, W. O.;Becker, M.;Luck, W.;Schuelke, M.;Neuhaus, P.",1997,Jun,,0,0,
587,Treatment of Wilson's disease with zinc: XIV. Studies of the effect of zinc on lymphocyte function,"Although administration of zinc to human subjects has been reported to interfere with lymphocyte function, this single report has never been confirmed or refuted. We have developed zinc as a lifelong therapy for patients with Wilson's disease. Interference with lymphocyte function occurring as a side effect of zinc therapy could produce serious problems in our patients. We evaluated lymphocyte mitogenic response and natural killer cell activity in patients with Wilson's disease treated for 5 years or longer with zinc, in comparison with normal controls, and found no differences. In a second study, we evaluated these same parameters in patients with Wilson's disease before and after 1 year of zinc therapy, and again found no significant differences. We have seen no indications of immune suppression or increased susceptibility to infections in our patients, who have now been treated with zinc for up to 15 years. We conclude that any side effects from compromised lymphocyte function caused by administration of zinc are not of concern to patients with Wilson's disease.","Copper/bl [Blood];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/im [Immunology];Humans;Killer Cells, Natural/de [Drug Effects];*Killer Cells, Natural/im [Immunology];*Lymphocyte Activation/de [Drug Effects];Male;Reference Values;Tumor Cells, Cultured;Zinc/bl [Blood];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Brewer, G. J.;Johnson, V.;Kaplan, J.",1997,Jun,,0,1,
588,[Acute hemolytic crisis as the initial manifestation of Wilson disease],"A 25-year-old woman who had delivered a normal child after a normal pregnancy four months ago, was suffering from a common cold. The latter was treated by tetracyclines. A few days later she developed an acute severe hemolysis. Moreover she had signs of hepatic failure which was characterized by a considerably reduced synthetic capacity of the liver but low serum aminotransferase levels and a proximal renal tubular disorder. With a negative Coombs test an autoimmune hemolytic anemia was unlikely. Therefore diagnostic procedures were directed at the cause of the liver injury. An increased urinary excretion of copper, strongly elevated levels of liver tissue copper and the detection of a Kayser-Fleischer ring by slit-lamp examination proved the diagnosis of Wilson's disease-presenting clinically only as severe hemolysis. Ceruloplasmin concentration in serum was in low normal range and not diagnostic.","Acute Disease;Adult;Anemia, Hemolytic/dt [Drug Therapy];*Anemia, Hemolytic/et [Etiology];Anemia, Hemolytic/pa [Pathology];Biopsy;Copper/bl [Blood];Diagnosis, Differential;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/pa [Pathology];Liver Function Tests;Penicillamine/ad [Administration & Dosage];*Puerperal Disorders/di [Diagnosis];Puerperal Disorders/dt [Drug Therapy];Puerperal Disorders/pa [Pathology];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Rath, H. C.;Enger, I. M.;Ruschoff, J.;Scholmerich, J.;Holstege, A.",1997,Mar,,0,0,
589,Pediatric Wilson's disease: presentation and management,"Eleven patients (4 males, 7 females) with Wilson's disease who presented before 18 years of age are described. The mean age onset of symptoms was 11.2 +/- 3.9 (SD) years. The mean age at diagnosis was 13.3 +/- 3.4 (SD) years. All patients had hepatic manifestations of the disease when diagnosed: cirrhosis (6 patients), chronic hepatitis (2) and fulminant hepatic failure (3). Three patients were asymptomatic at diagnosis. Two of the symptomatic patients presented with new undescribed manifestations: one with blurred vision and the other with acalculous cholecystitis. At diagnosis, 6 patients had Kayser Fleischer rings and 5 had hemolytic anemia. The three patients with fulminant hepatic failure had hemolysis with relatively low serum aminotransferase and alkaline phosphatase levels, possibly helpful findings for rapid diagnosis of Wilson's disease in such presentation. Ten patients were treated with penicillamine. Liver transplantation was performed in 4 patients, 2 of which presented with fulminant hepatic failure. One patient died while waiting for liver transplantation, the remainder of the patients live free of symptoms. It is important to be aware of the different manifestations of Wilson's disease in the pediatric population, in order to make appropriate evaluations in a timely manner to facilitate early diagnosis and appropriate treatment.","Adolescent;Anemia, Hemolytic/et [Etiology];Chelating Agents/tu [Therapeutic Use];Child;Child, Preschool;Cholecystitis/et [Etiology];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Liver Cirrhosis/et [Etiology];Liver Failure/et [Etiology];Liver Transplantation;Male;Penicillamine/tu [Therapeutic Use];Vision Disorders/et [Etiology];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","On, A.;Choi, H. J.;Heyman, M. B.;Vargas, J.;Ament, M. E.",1997,Mar-Apr,,0,0,
590,Problems in diagnosis and management of Wilson's disease in India,,*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;India;Penicillamine/tu [Therapeutic Use];Self-Help Groups;GNN1DV99GX (Penicillamine),"Pandit, A.;Bhave, S.",1996,Oct,,0,0,
591,Regression of Kayser-Fleischer rings during oral zinc therapy: correlation with systemic manifestations of Wilson's disease,"Fourteen patients presenting with neuropsychiatric manifestations of Wilson's disease were treated with oral tetrathiomolybdate (TM) for 8 weeks followed by oral zinc (Zn) maintenance therapy. The patients were evaluated prospectively at baseline and at yearly intervals for up to 5 years by slit-lamp biomicroscopy and photography, quantitative neurologic and speech pathology examinations, 24-h urine copper collection, and a quantitative scoring of magnetic resonance imaging (MRI) of the brain. Kayser-Fleischer (KF) ring size decreased significantly during the 5-year study period (p < 0.0001). Although results of neurologic examination, speech pathology examination, and 24-h urine copper level analysis in symptomatic Wilson's disease patients improved during the study period, KF ring regression did not correlate with the improvement in these clinical parameters (p > 0.05). However, there was a correlation between MRI scores and KF ring regression (p = 0.02). Anticopper therapy with TM followed by zinc maintenance therapy is a safe and effective treatment for patients with neurologically symptomatic Wilson's disease. This treatment leads to reduction in KF ring size; however, KF ring reduction is not a good predictor of clinical improvement for patients with neuropsychiatric manifestations of Wilson's disease.","Administration, Oral;Adolescent;Adult;Brain Diseases/pa [Pathology];Copper/ur [Urine];Cornea/de [Drug Effects];*Cornea/pp [Physiopathology];Corneal Diseases/dt [Drug Therapy];*Corneal Diseases/pp [Physiopathology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Magnetic Resonance Imaging;Male;Molybdenum/ad [Administration & Dosage];Molybdenum/tu [Therapeutic Use];Prospective Studies;Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc)","Esmaeli, B.;Burnstine, M. A.;Martonyi, C. L.;Sugar, A.;Johnson, V.;Brewer, G. J.",1996,Nov,,0,0,
592,Treatment of Wilson disease with ammonium tetrathiomolybdate. II. Initial therapy in 33 neurologically affected patients and follow-up with zinc therapy,"OBJECTIVE: To test the efficacy and toxic effects of ammonium tetrathiomolybdate in the initial treatment of a relatively large series of patients with neurologic symptoms and signs caused by Wilson disease. Two key aspects of efficacy are to preserve the neurologic function present at the onset of therapy and to maximize the opportunity for long-term recovery. DESIGN: An open study of 33 patients treated for 8 weeks each, including further follow-up data on the original 17 patients. Neurologic function was evaluated by frequent quantitative neurologic and speech pathology examinations. Several copper-related variables were studied to evaluate the effect of the drug on copper, and several biochemical and clinical variables were studied to evaluate potential toxic effects. Patients were then followed up at yearly intervals, with follow-up periods of 1 to 8 years reported. SETTING: A university hospital referral setting. INTERVENTION: Patients were generally treated for 8 weeks with tetrathiomolybdate, followed by zinc maintenance therapy. MAIN OUTCOME MEASURES: Neurologic function was evaluated by quantitative neurologic and motor speech examinations and magnetic resonance imaging scans of the brain. RESULTS: During the 8 weeks of tetrathiomolybdate administration, only 1 of the 33 patients showed deterioration in neurologic function. Copper status and potential further toxic effects were generally well controlled quickly. Evaluation of data from individual patients revealed evidence of a toxic side effect in only 1 patient, who exhibited reversible anemia. During the ensuing period of follow-up of 1 to 6 years, neurologic recovery in most patients was good to excellent. CONCLUSIONS: Tetrathiomolybdate appears to be an excellent form of initial treatment in patients with Wilson disease who present with neurologic symptoms and signs. In contrast to penicillamine therapy, initial treatment with tetrathiomolybdate rarely allows further, often irreversible, neurologic deterioration.",Adolescent;Adult;Female;Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver/de [Drug Effects];Liver/pp [Physiopathology];Male;Molybdenum/ae [Adverse Effects];*Molybdenum/tu [Therapeutic Use];*Nervous System/pp [Physiopathology];Neurologic Examination;Speech-Language Pathology/mt [Methods];Time Factors;Treatment Outcome;*Zinc/tu [Therapeutic Use];81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc),"Brewer, G. J.;Johnson, V.;Dick, R. D.;Kluin, K. J.;Fink, J. K.;Brunberg, J. A.",1996,Oct,,0,1,
593,Recurrent hypokalemic muscle weakness as an initial manifestation of Wilson's disease,A 24-year-old man had several episodes of hypokalemic muscle weakness of undetermined etiology since the age of 13 years. Wilson's disease (WD) was not diagnosed until the age of 18 when wing-beating tremor in the left upper limb was noted. Renal function study revealed incomplete proximal renal tubular acidosis. The hypokalemic muscle weakness and wing-beating tremor had subsided after long-term penicillamine therapy. The present case indicates that recurrent hypokalemic paralysis due to renal tubular acidosis is a rare initial presentation of WD and may respond to penicillamine therapy.,"Acidosis, Renal Tubular/pa [Pathology];Adolescent;Atrophy;Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Humans;*Hypokalemia/et [Etiology];Male;*Muscle Weakness/et [Etiology];Paralysis/co [Complications];Penicillamine/tu [Therapeutic Use];Recurrence;Tomography, X-Ray Computed;Tremor/co [Complications];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Chu, C. C.;Huang, C. C.;Chu, N. S.",1996,,,0,0,
594,Acquired sideroblastic anaemia induced by a copper-chelating agent,"Acquired sideroblastic anaemia may be related to drugs and other chemicals that inhibit the activity of mitochondrial enzymes involved in haem synthesis. We report a case of secondary acquired sideroblastic anaemia following administration of triethylene tetramine dihydrochloride (trientine), a second-line copper-chelating agent used in the treatment of Wilson's disease. The anaemia improved after dose reduction of trientine. The mechanism of induction of sideroblastic anaemia in this case is unclear, but trientine does not appear to alter the function of two key mitochondrial haem enzymes, and may instead act directly on mitochondrial iron metabolism.","Adolescent;*Anemia, Sideroblastic/ci [Chemically Induced];*Chelating Agents/ae [Adverse Effects];*Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Trientine/ae [Adverse Effects];0 (Chelating Agents);789U1901C5 (Copper);SJ76Y07H5F (Trientine)","Perry, A. R.;Pagliuca, A.;Fitzsimons, E. J.;Mufti, G. J.;Williams, R.",1996,Jul,,0,0,
595,Wilson's disease: resolution of MRI lesions following long-term oral zinc therapy,"A 28-year-old man with Wilson's disease developed neurological deterioration after a low-dose of d-penicillamine treatment for 2 weeks. He showed an akinetic rigid syndrome with generalized dystonia. Brain magnetic resonance images (MRI) on T2 and proton weighted images showed an increased signal intensity over the thalamus, basal ganglia and brainstem, especially the midbrain and pons. After treatment had been changed to zinc sulphate, the akinetic-rigid syndrome and dystonia were improved slowly in the following 4 years. Serial MRI studies showed a gradual resolution of the lesions. His current neurological status was almost normal except for dysarthria and mild intention tremor.","Administration, Oral;Adult;*Brain/de [Drug Effects];Brain/pa [Pathology];Dose-Response Relationship, Drug;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Long-Term Care;*Magnetic Resonance Imaging;Male;Neurologic Examination/de [Drug Effects];Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];*Sulfates/ad [Administration & Dosage];*Zinc Compounds/ad [Administration & Dosage];Zinc Sulfate;0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine)","Huang, C. C.;Chu, N. S.",1996,Feb-Mar,,0,0,
596,Wilson disease: genetic basis of copper toxicity and natural history,"The discovery that the gene for Wilson disease encodes a copper-transporting ATPase has greatly improved our understanding of the pathophysiology of this disorder and of copper metabolism in humans. The abundance of disease-specific mutations and their location at multiple sites across the genome have limited molecular genetic diagnosis to kindred of known patients, and confirm the necessity for de novo screening by well-proven clinical and biochemical means. It is uncertain whether the variety of specific mutations will account for the wide range of presenting clinical signs and symptoms of Wilson disease, and environmental and extragenic factors are likely to be important contributing factors. Chelation therapy with penicillamine and trientine remain effective treatment for most symptomatic hepatic and neurologic Wilson disease. Zinc salts may be used for some asymptomatic patients, and OLT for fulminant hepatitis and patients for whom pharmacotherapy is ineffective. The chelating agent tetrathiomolybdate is under investigation for the treatment of neurologic Wilson disease. Gene therapy is the new horizon for treatment of Wilson disease. However, the ability to treat this disorder effectively by this means awaits further characterization of the gene product and more efficient methods for gene delivery to all hepatocytes in the liver. [References: 92]","Adenosine Triphosphatases/ge [Genetics];Carrier Proteins/ge [Genetics];*Cation Transport Proteins;Chelating Agents/tu [Therapeutic Use];Chelation Therapy;Chromosome Mapping;*Copper/ae [Adverse Effects];Copper/me [Metabolism];Environment;Genetic Therapy;Genome, Human;Hepatitis/su [Surgery];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;Liver Transplantation;Molybdenum/tu [Therapeutic Use];Mutation/ge [Genetics];Penicillamine/tu [Therapeutic Use];Risk Factors;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0 (Carrier Proteins);0 (Cation Transport Proteins);0 (Chelating Agents);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 3-6-1 (Adenosine Triphosphatases);EC 3-6-3-4 (Wilson disease protein);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Schilsky, M. L.",1996,Feb,https://dx.doi.org/10.1055/s-2007-1007221,0,0,
597,Wilson's disease and mental disturbances,,"Adult;Copper/bl [Blood];Diagnosis, Differential;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Humans;Male;*Neurocognitive Disorders/di [Diagnosis];Neurocognitive Disorders/dt [Drug Therapy];Neurocognitive Disorders/px [Psychology];Penicillamine/tu [Therapeutic Use];*Schizophrenia/di [Diagnosis];Schizophrenia/dt [Drug Therapy];Schizophrenic Psychology;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Vitorovic, S.;Lieina, M.",1996,Mar,,0,0,
598,Successful medical treatment of severely decompensated Wilson disease,"Delayed response to medical treatment sometimes leads to unnecessary liver transplantation in patients with severely decompensated Wilson disease. We report the course of five patients (mean age 13.4 years, range 11 to 15 years) with severely decompensated Wilson disease who were successfully treated medically. Prothrombin time improved after a minimum of 1 month and returned to normal within 3 months to 1 year or more.",Adolescent;Anti-Bacterial Agents/ad [Administration & Dosage];*Anti-Bacterial Agents/tu [Therapeutic Use];Chelation Therapy;Child;Copper/ur [Urine];Female;Hemolysis;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/th [Therapy];Humans;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Prothrombin Time;Sulfates/ad [Administration & Dosage];*Sulfates/tu [Therapeutic Use];Zinc Compounds/ad [Administration & Dosage];*Zinc Compounds/tu [Therapeutic Use];Zinc Sulfate;0 (Anti-Bacterial Agents);0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Santos Silva, E. E.;Sarles, J.;Buts, J. P.;Sokal, E. M.",1996,Feb,,0,1,
599,Neuromuscular transmission and acetylcholine receptor antibodies in penicillamine-treated Wilson's disease patients,,"Adolescent;*Autoantibodies/an [Analysis];Child;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Muscles/ir [Innervation];*Penicillamine/tu [Therapeutic Use];*Receptors, Cholinergic/im [Immunology];*Synaptic Transmission;0 (Autoantibodies);0 (Receptors, Cholinergic);GNN1DV99GX (Penicillamine)","Anlar, B.;Kuruoglu, R.;Varli, K.;Topcu, M.",1996,May,,0,0,
600,Present interpretation of the role of copper in Indian childhood cirrhosis,"A common killer disease of the past, Indian childhood cirrhosis (ICC), which became preventable and treatable in the early 1990s, is now rare. ICC must be clearly distinguished in Indian children from other chronic liver disorders including Wilson disease. Grossly increased hepatic, urinary, and serum copper concentrations are characteristic of ICC. These increased concentrations are easily demonstrated histologically with orcein-rhodanine staining. Environmental ingestion of copper appears to be the most plausible explanation for ICC, as shown by feeding histories, the prevention of ICC is siblings and in the Pune district by a change in feeding vessels, and the dramatic reduction in incidence of ICC throughout India. The nature and role of a second factor in the causation of ICC remains unclear, although an inherited defect in copper metabolism is strongly suspected. ICC, however, does not appear to be a straightforward early onset of Wilson disease because ceruloplasmin is consistently normal and clinical and histologic recovery is maintained in the long term despite withdrawal of D-penicillamine therapy. Descriptions of an ICC-like illness in the West suggest that different mechanisms (environmental, genetic, or both) can lead to the same end-stage liver disease: copper-associated childhood cirrhosis. ICC probably represents a specific form of copper-associated childhood cirrhosis that requires high environmental copper ingestion for its full expression. [References: 59]","Animals;Child, Preschool;*Copper/ae [Adverse Effects];Copper/me [Metabolism];Diet/ae [Adverse Effects];Female;Food Handling;Humans;Incidence;India/ep [Epidemiology];Infant;Infant, Newborn;Liver/de [Drug Effects];Liver/pa [Pathology];Liver Cirrhosis/ep [Epidemiology];*Liver Cirrhosis/et [Etiology];Liver Cirrhosis/pa [Pathology];Male;Milk/ch [Chemistry];789U1901C5 (Copper)","Pandit, A.;Bhave, S.",1996,May,,0,0,
601,Wilson's disease: an update,,"Copper/pk [Pharmacokinetics];Diagnosis, Differential;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Liver Function Tests;Neurologic Examination/de [Drug Effects];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Garg, R. K.;Nag, D.",1995,May,,0,0,
602,Chemometric methods applied to an ICP-AES study of chemical element distributions in autopsy livers from subjects affected by Wilson and beta-thalassemia,"The concentrations of seven elements (Ca, Cu, Fe, Mg, P, S and Zn) in three autopsy livers (from two beta-thalassemic patients and one Wilson's disease patient) were determined by ICP-AES technique. At autopsy the three livers were subdivided into a large number of samples for a detailed study of the distribution of Fe and Cu, the accumulation of which characterizes the two diseases. In the same samples Ca, Mg, P, S and Zn concentrations were also determined in order to study significant variations or anomalous trends that could help identify these diseases. Our results generally show a good coincidence with literature data within the limits of sample variability. Based on Factor Analysis as well as Regression Analysis there is evidence of a high correlation between Fe and P contents in beta-thalassemia. The latter finding led us to propose tentatively an accumulation of Fe as a complex with P-containing molecules.",Adult;Autopsy;Calcium/an [Analysis];Copper/an [Analysis];*Elements;*Hepatolenticular Degeneration/me [Metabolism];Humans;In Vitro Techniques;Iron/an [Analysis];*Liver/ch [Chemistry];Magnesium/an [Analysis];Phosphorus/an [Analysis];*Spectrum Analysis/mt [Methods];Sulfur/an [Analysis];Zinc/an [Analysis];*beta-Thalassemia/me [Metabolism];0 (Elements);27YLU75U4W (Phosphorus);70FD1KFU70 (Sulfur);789U1901C5 (Copper);E1UOL152H7 (Iron);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc);SY7Q814VUP (Calcium),"Aragoni, M. C.;Crisponi, G.;Nurchi, V. M.;Silvagni, R.;Sciot, R.;Ambu, R.;Costa, V.;Faa, G.",1995,Dec,,0,0,
603,Neurological Wilson's disease studied with magnetic resonance imaging and with positron emission tomography using dopaminergic markers,"Four patients with neurological Wilson's disease were investigated using magnetic resonance imaging (MRI) and positron emission tomography (PET). All patients had dystonia as their major clinical manifestation but also had dysarthria and at the presentation of the disease had choreoathetoid movements in at least one limb. A multitracer approach with PET was used to visualize various aspects of dopaminergic function; [11C]-(+)-nomifensine (NMF), [11C]raclopride (RAC) and [11C]-L-DOPA (one patient). Correlation analysis of RAC and NMF binding as well as putamen/caudate uptake ratios showed corresponding reductions. The patient investigated with [11C]-L-DOPA had a normal striatal uptake. Generally, structural changes as shown by MRI corresponded to reductions both in NMF and RAC binding. There was no evident correspondence between PET findings and the severity of clinical symptoms seen in the individual patient. In two patients with discrete neurological impairment at the time of investigation, PET showed serious presynaptic dopaminergic lesions in the putamen. Our data suggest that the striatal degeneration seen in Wilson's disease comprises a complex pathology involving both afferent and efferent projections. The discrete neurological impairment seen in some patients with gross striatal pathology might be due to concomitant lesions in functionally counteracting basal ganglia circuits.","Adult;Anti-Bacterial Agents/ad [Administration & Dosage];Anti-Bacterial Agents/tu [Therapeutic Use];Binding Sites;*Brain/dg [Diagnostic Imaging];*Brain/pp [Physiopathology];Caudate Nucleus/me [Metabolism];Caudate Nucleus/pp [Physiopathology];Ceruloplasmin/an [Analysis];Copper/ur [Urine];Corpus Striatum/me [Metabolism];Corpus Striatum/pp [Physiopathology];Dopamine Antagonists/tu [Therapeutic Use];Dysarthria;Dystonia;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Nomifensine;Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];Putamen/me [Metabolism];Putamen/pp [Physiopathology];Raclopride;Salicylamides;*Tomography, Emission-Computed;0 (Anti-Bacterial Agents);0 (Dopamine Antagonists);0 (Salicylamides);1LGS5JRP31 (Nomifensine);430K3SOZ7G (Raclopride);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Westermark, K.;Tedroff, J.;Thuomas, K. A.;Hartvig, P.;Langstrom, B.;Andersson, Y.;Hornfeldt, K.;Aquilonius, S. M.",1995,Sep,https://dx.doi.org/10.1002/mds.870100511,0,0,
604,Mechanisms of pennicillamine and zinc in the treatment of Wilson's disease,,Adolescent;Adult;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;*Penicillamine/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Farinati, F.;Cardin, R.;Mestriner, C.;Sturniolo, G. C.;Naccarato, R.",1995,Dec,,0,0,
605,D-penicillamine-induced myasthenia gravis: diagnosis obscured by coexisting chronic obstructive pulmonary disease,"D-penicillamine, a drug used to treat rheumatoid arthritis, Wilson's disease, and cystinuria, can cause myasthenia gravis. Fortunately, the myasthenia typically resolves after discontinuation of the drug. The diagnosis may be missed if weakness is blamed on a patient's underlying disease(s), in particular, rheumatoid arthritis. Reported here are the cases of two patients with chronic obstructive lung disease who were taking D-penicillamine for rheumatoid arthritis, then experienced increasing respiratory failure. At first, their problem seemed to stem from chronic lung disease, but further evaluation revealed the cause of the hypoventilation to be D-penicillamine-induced myasthenia gravis.","Aged;Arthritis, Rheumatoid/co [Complications];Arthritis, Rheumatoid/dt [Drug Therapy];Female;Humans;Hypoventilation/et [Etiology];*Lung Diseases, Obstructive/co [Complications];Male;Middle Aged;*Myasthenia Gravis/ci [Chemically Induced];Myasthenia Gravis/co [Complications];Myasthenia Gravis/di [Diagnosis];*Penicillamine/ae [Adverse Effects];Respiratory Insufficiency/et [Etiology];GNN1DV99GX (Penicillamine)","Adelman, H. M.;Winters, P. R.;Mahan, C. S.;Wallach, P. M.",1995,Apr,,0,0,
606,Copper-induced acute rhabdomyolysis in Wilson's disease,"Wilson's disease is a lethal defect in copper metabolism causing a continual increase in tissue copper concentrations that become toxic to the liver, brain, kidney, eye, skeletal system, and several other tissues and organs. The liver is unique among these in being both the site of the etiologic biochemical abnormality and the organ that is always affected by copper toxicosis. Although myocardial muscle involvement has been reported in association with Wilson's disease, copper deposits in peripheral muscle tissue have not yet been described. A case of a young patient with Wilson's disease who developed recurrent episodes of acute rhabdomyolysis is presented, and the accumulation of copper in muscle tissue as a possible complication is discussed.",Acetates/tu [Therapeutic Use];Acetic Acid;Acute Disease;Adolescent;Biopsy;*Copper/me [Metabolism];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Muscles/me [Metabolism];Muscles/pa [Pathology];Penicillamine/tu [Therapeutic Use];Recurrence;*Rhabdomyolysis/et [Etiology];Rhabdomyolysis/pa [Pathology];0 (Acetates);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);Q40Q9N063P (Acetic Acid),"Propst, A.;Propst, T.;Feichtinger, H.;Judmaier, G.;Willeit, J.;Vogel, W.",1995,Mar,,0,0,
607,Hydroxyl radical formation from cuprous ion and hydrogen peroxide: a spin-trapping study,"Copper toxicity has been presumed to involve catalytic hydroxyl radical (.OH) formation from hydrogen peroxide. Addition of Cu1+ to a solution containing ethanol or dimethylsulfoxide (Me2SO) and the spin-trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) results in formation of the alpha-hydroxyethyl radical or methyl radical adduct of 4-POBN, respectively. Adduct formation was prevented by inclusion of catalase, but not by superoxide dismutase. Inclusion of exogenous H2O2 in the reaction mixture increased the yield of ethanol- or Me2SO-derived radical adduct and also enhanced the formation of secondary radical adducts, including 4-POBN/.H and the methyl radical adduct of 2-methyl-2-nitrosopropane. The alpha-hydroxyethyl adduct of 4-POBN is rapidly decomposed in the presence of copper, but not iron salts, whereas the methyl radical adduct is relatively stable in the presence of inorganic copper. The total concentration of radical adduct detected from the reaction between Cu1+ and H2O2, determined by comparison of the integrated spectral intensity with that of the stable 2,2,6,6-tetramethyl-1-piperidinyloxy free radical, was only 1-5% of the maximum amount predicted assuming radical adduct formation from all of the added copper. A variety of copper chelators inhibit formation of carbon-centered radical adducts of 4-POBN, including penicillamine and triethylenetetramine, which are the primary drugs used to treat the copper metabolism disorder Wilson's disease. The results provide clear evidence for hydroxyl radical formation from Cu1+ and H2O2 (either added or formed during the autoxidation of reduced copper.","*Cations, Monovalent/ch [Chemistry];Cations, Monovalent/to [Toxicity];Chelating Agents/ch [Chemistry];*Copper/ch [Chemistry];Copper/to [Toxicity];Cyclic N-Oxides;Electron Spin Resonance Spectroscopy;Hydrogen Peroxide/ch [Chemistry];*Hydroxyl Radical/ch [Chemistry];Oxidation-Reduction;Spin Labels;0 (Cations, Monovalent);0 (Chelating Agents);0 (Cyclic N-Oxides);0 (Spin Labels);3352-57-6 (Hydroxyl Radical);7170JZ1QF3 (5,5-dimethyl-1-pyrroline-1-oxide);789U1901C5 (Copper);BBX060AN9V (Hydrogen Peroxide);C955P95064 (cuprous chloride)","Gunther, M. R.;Hanna, P. M.;Mason, R. P.;Cohen, M. S.",1995,Jan 10,https://dx.doi.org/10.1006/abbi.1995.1068,0,0,
608,Psychosis in an adolescent patient with Wilson's disease: effects of chelation therapy,"Wilson's disease is a rare genetic disorder involving the liver and brain, with onset frequently in adolescence. Psychiatric symptoms are often the first manifestation of the disease and can obscure the diagnosis. Chelation therapy can reverse the fatal outcome of untreated patients, so early detection is critically important. This paper describes an adolescent with Wilson's disease who, after initiation of penicillamine therapy, developed florid psychosis that improved as copper levels were decreased and that did not require use of neuroleptic medication.",Adolescent;Copper/ur [Urine];Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Hepatolenticular Degeneration/ur [Urine];Humans;Male;*Neurocognitive Disorders/dt [Drug Therapy];Neurocognitive Disorders/px [Psychology];Neurocognitive Disorders/ur [Urine];Neuropsychological Tests;*Penicillamine/tu [Therapeutic Use];Recurrence;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"McDonald, L. V.;Lake, C. R.",1995,Mar-Apr,,0,0,
609,"The mechanisms of penicillamine, trientine, and zinc in the treatment of Wilson's disease",,*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];*Trientine/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Yarze, J. C.",1995,Jun,,0,0,
610,Interactions of zinc and molybdenum with copper in therapy of Wilson's disease,"We review two newer treatments for Wilson's disease that each use an interaction of another metal with Cu to bring about therapeutic benefit. The two metals are Zn, in the form of the acetate salt, and Mo in the form of ammonium tetrathiomolybdate (TM). Zn, which blocks absorption of Cu in the intestine by inducing intestinal cell metallothionein, is used for maintenance therapy, treatment of the presymptomatic patient from the beginning, and treatment of the pregnant patient. TM, which complexes Cu in a tripartite complex with protein, is used for the initial treatment of neurologically presenting patients. [References: 31]",Copper/ad [Administration & Dosage];*Copper/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/ad [Administration & Dosage];*Molybdenum/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);J41CSQ7QDS (Zinc),"Brewer, G. J.",1995,Jan-Feb,,0,0,
611,Plasma copper and antioxidant status in Wilson's disease,"It has been demonstrated that the level of serum copper unbound to ceruloplasmin (loosely bound copper) is increased in Wilson's disease, although the total serum copper concentration is usually low, reflecting a low ceruloplasmin level. To assess the contribution of free radical reactions catalyzed by nonceruloplasmin copper to the development of complications in this disease, we investigated copper and antioxidant status in four untreated patients who had hepatic dysfunction with or without hemolytic anemia and made a comparison with five patients controlled on penicillamine therapy and 19 age-matched healthy children. We found that loosely bound copper in plasma measured by the phenanthroline assay was detectable in three of four untreated patients with Wilson's disease, but was not detectable in the patients during therapy or in the healthy controls. Among the various antioxidants, the ascorbate and urate levels were markedly reduced before treatment (mean +/- SD, 23 +/- 16 microM for ascorbate and 90 +/- 59 microM for urate) compared with the values in the patients during treatment with penicillamine (67 +/- 19 and 302 +/- 78 microM, p < 0.05) and in control children (60 +/- 8 and 254 +/- 48 microM, p < 0.05). We also demonstrated that the plasma concentration of allantoin, an oxidation product of uric acid and a possible marker of radical generation in vivo, was markedly elevated in the untreated patients (11.0 +/- 1.8 versus 4.3 +/- 0.5 microM in patients on therapy and 6.5 +/- 0.8 microM in controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",Allantoin/bl [Blood];*Antioxidants/an [Analysis];Ascorbic Acid/bl [Blood];Biomarkers/bl [Blood];Ceruloplasmin/an [Analysis];Child;*Copper/bl [Blood];Female;Free Radicals;*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];Thiobarbituric Acid Reactive Substances/an [Analysis];Uric Acid/bl [Blood];Vitamin E/bl [Blood];0 (Antioxidants);0 (Biomarkers);0 (Free Radicals);0 (Thiobarbituric Acid Reactive Substances);1406-18-4 (Vitamin E);268B43MJ25 (Uric Acid);344S277G0Z (Allantoin);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);PQ6CK8PD0R (Ascorbic Acid),"Ogihara, H.;Ogihara, T.;Miki, M.;Yasuda, H.;Mino, M.",1995,Feb,https://dx.doi.org/10.1203/00006450-199502000-00016,0,1,
612,Treatment of the neurologic manifestations of Wilson's disease,,Dimercaprol/tu [Therapeutic Use];Hepatolenticular Degeneration/ci [Chemically Induced];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Molybdenum/tu [Therapeutic Use];Nervous System Diseases/ci [Chemically Induced];*Nervous System Diseases/dt [Drug Therapy];Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];0CPP32S55X (Dimercaprol);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine),"Scheinberg, I. H.;Sternlieb, I.",1995,Apr,,0,0,
613,[Lupus erythematosus and liver diseases],,"Autoimmune Diseases/et [Etiology];Budd-Chiari Syndrome/et [Etiology];Chelating Agents/ae [Adverse Effects];Hepatitis/et [Etiology];Hepatitis/im [Immunology];Hepatitis, Chronic/et [Etiology];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/bs [Blood Supply];*Liver Diseases/et [Etiology];Liver Transplantation;Lupus Erythematosus, Systemic/ci [Chemically Induced];*Lupus Erythematosus, Systemic/co [Complications];Lupus Erythematosus, Systemic/dt [Drug Therapy];Penicillamine/ae [Adverse Effects];Vasculitis/et [Etiology];0 (Chelating Agents);GNN1DV99GX (Penicillamine)","Barthel, H. R.;Hiepe, F.",1995,Sep 15,https://dx.doi.org/10.1055/s-2008-1055473,0,0,
614,Effect of growth hormone on IGF-I levels in a patient with growth hormone deficiency and Wilson disease,"This is a case report of a boy with a combination of two rare disorders:growth hormone deficiency (GHD) and Wilson disease. To our knowledge, no comparable case has yet been published in the literature. GHD was diagnosed at the age of 4.5 years (height standard deviation score (SDS) -4.85). However, because of a difficult family background, growth hormone (GH) therapy could not be started. The boy was not seen again until the age of 7.7 years (height SDS -4.77), when GHD was reconfirmed and GH therapy could be initiated (dose 0.6 IU/kg/week). At that time, elevated liver enzymes (GPT 128 U/l, GOT 67 U/l, gamma-GT 28 U/l) confused diagnostic procedures. On GH, growth velocity SDS increased from -1.86 to +4.50 in the first year and +3.87 in the second year, and height SDS increased to -4.26 and -3.59. However, serum IGF-I levels did not normalize (max. 67 ng/ml), and liver enzymes were still elevated. At the age of 10 years, Wilson disease was diagnosed in view of low concentration of serum ceruloplasmin, elevated urinary copper excretion and high copper content in a liver biopsy sample. Under a combined therapy with D-penicillamine and GH, serum liver enzymes decreased, and IGF-I levels increased to normal. Height SDS for chronological age has improved constantly.","Ceruloplasmin/me [Metabolism];Child, Preschool;Copper/an [Analysis];Copper/ur [Urine];*Growth Hormone/df [Deficiency];*Growth Hormone/tu [Therapeutic Use];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Humans;*Insulin-Like Growth Factor I/me [Metabolism];Liver/ch [Chemistry];Liver/en [Enzymology];Male;Penicillamine/tu [Therapeutic Use];Weight Gain;67763-96-6 (Insulin-Like Growth Factor I);789U1901C5 (Copper);9002-72-6 (Growth Hormone);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Koch, A.;Dorr, H. G.;Gerling, S.;Behrens, R.;Bohles, H. J.",1995,,,0,0,
615,MRI of the brain in Wilson disease: T2 signal loss under therapy,"Repeat examinations in a de novo patient with Wilson disease revealed an expansion of decreased signal intensities in the basal ganglia on T2-weighted imaging after initiation of copper trapping therapy. Since marked clinical improvement was associated with continued urinary copper excretion, iron depositioning in exchange for copper might explain these findings.",Adult;Basal Ganglia/pa [Pathology];*Brain/pa [Pathology];Follow-Up Studies;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Male;Penicillamine/tu [Therapeutic Use];Time Factors;GNN1DV99GX (Penicillamine),"Engelbrecht, V.;Schlaug, G.;Hefter, H.;Kahn, T.;Modder, U.",1995,Jul-Aug,,0,1,
616,Long-term treatment of Wilson's disease with triethylene tetramine dihydrochloride (trientine),"Long-term treatment with triethylene tetramine dihydrochloride, (trientine, TETA) was evaluated in 19 patients with Wilson's disease (WD). Two were given the drug as first choice and 17 after treatment with penicillamine. The change was made because of side-effects, lack of improvement or worsening of neurological symptoms. All penicillamine-induced side-effects reverted. Thirteen patients still receive trientine, and the mean total observation time on this treatment is 8.5 years/patient. Seven of the 13 are free from symptoms related to WD, five have mild to moderate neurological symptoms, mainly dysarthria. One patient with neurological symptoms who received trientine from the start of treatment deteriorated rapidly and is now severely dystonic. The symptoms initially worsened and later improved in one patient. All other patients improved during trientine treatment. Three patients died: two from a multifocal cancer including the liver and one non-complier from a ruptured spleen. Two patients underwent liver transplantation for progressive liver failure: one non-complier and one with liver cirrhosis whose liver function deteriorated despite treatment; both are now free from symptoms. Unexpectedly, two patients developed a serious colitis, one with duodenitis as well, that improved after withdrawal of the drug. No other unfavourable effects of trientine were recorded.",Adolescent;Adult;Biopsy;*Chelating Agents/tu [Therapeutic Use];Child;Colon/pa [Pathology];Drug Administration Schedule;Duodenum/pa [Pathology];Female;Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Intestinal Mucosa/pa [Pathology];Liver/pa [Pathology];Male;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Dahlman, T.;Hartvig, P.;Lofholm, M.;Nordlinder, H.;Loof, L.;Westermark, K.",1995,Sep,,0,0,
617,Wilson's disease: a new gene and an animal model for an old disease,"Wilson's disease is an autosomal recessive, inherited disorder of copper metabolism. In normal individuals, copper homeostasis is controlled by the balance between intestinal absorption of dietary copper and hepatic excretion of excess copper in bile. In Wilson's disease, hepatic copper is neither excreted in bile nor incorporated into ceruloplasmin and copper accumulates to toxic levels. The Wilson's disease gene (WND) encodes a putative copper-transporting protein that is expressed almost exclusively in the liver. The predicted structure of the protein product is that of a P-type ATPase with striking homology to bacterial copper transporters and the gene product of another inherited disorder of copper metabolism, Menkes' disease. A rat model of Wilson's disease has recently been identified. The Long-Evans Cinnamon (LEC) rat manifests elevated hepatic copper, defective incorporation of copper into ceruloplasmin, and reduced biliary excretion of copper. The rat homologue of the WND is abnormal in LEC rats. Clinical manifestations of Wilson's disease arise directly from copper-induced damage to hepatocytes (hepatic presentation) or indirectly after the release of copper from the liver with subsequent damage to the brain (neuropsychiatric presentation) and other organs. Genetic heterogeneity (different mutations in a single gene) may account for some of the variability in Wilsonian presentations. The diagnosis of Wilson's disease depends on the demonstration of disordered copper metabolism, manifested as elevated urinary and hepatic copper and low ceruloplasmin levels. However, none of the abnormal findings in Wilson's disease is pathognomonic. Genetic diagnosis, in the absence of family studies, is likely to be difficult since many different mutations result in the disease. Management of Wilson's disease involves decreasing excess levels of copper accumulated in the liver, brain, and other organs. Copper chelation therapy, to increase urinary excretion of copper, is the mainstay of treatment. In addition, oral zinc therapy may be useful at decreasing absorption of dietary copper and rendering tissue copper nontoxic, by increasing the formation of complexes with copper-binding proteins. Liver transplantation can be necessary for individuals with acute hepatic failure or complications of cirrhosis. Gene therapy may evolve in the future; however, medical management is effective in most patients. [References: 121]","*Amino Acid Sequence;Animals;Chromosome Mapping;Cloning, Molecular;Copper/me [Metabolism];Disease Models, Animal;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Humans;Mice;Molecular Sequence Data;Rats;789U1901C5 (Copper)","Cuthbert, J. A.",1995,Aug,,0,0,
618,Diagnosis of Wilson's disease in an asymptomatic sibling by DNA linkage analysis,"The molecular genetic diagnosis of Wilson's disease in the 5-year-old sister of a patient with Wilson's disease is reported. The girl was clinically free of disease and had no conventional biochemical markers of Wilson's disease (i.e., normal ceruloplasmin, normal copper in the serum, normal 24-hour urinary copper excretion). Diagnosis with restriction fragment length polymorphisms and a nonradioactive polymerase chain reaction-based analysis with microsatellite markers showed her to be homozygous for the disease-associated markers. A liver biopsy was performed, and a 20-fold increased liver copper content confirmed the diagnosis. The child was treated with chelation therapy with D-penicillamine. The report of this study clearly shows the advantage of DNA linkage analysis (especially polymerase chain reaction) over conventional laboratory methods for presymptomatic diagnosis of Wilson's disease before irreparable liver and neurological damage occurs. The only limitation of this DNA-based diagnosis is the fact that it is only applicable in siblings of an index patient whose diagnosis was made by phenotypic criteria.","Adult;Biopsy;Child;Child, Preschool;Copper/an [Analysis];*DNA/an [Analysis];Family Health;Female;*Genetic Linkage;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/ch [Chemistry];Liver/pa [Pathology];Male;Pedigree;Polymerase Chain Reaction;Polymorphism, Restriction Fragment Length;789U1901C5 (Copper);9007-49-2 (dna)","Maier-Dobersberger, T.;Mannhalter, C.;Rack, S.;Granditsch, G.;Kaserer, K.;Korninger, L.;Steindl, P.;Gangl, A.;Ferenci, P.",1995,Dec,,0,0,
619,Wilson's disease in pregnancy,Patients with Wilson's disease contemplating pregnancy should have their hepatic function and copper status assessed. We report a case of a pregnant woman with Wilson's disease with compromised hepatic function. The medical problems and controversy of prescribing treatment are discussed.,Adolescent;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;*Liver/pp [Physiopathology];Male;Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications;Pregnancy Outcome;Trientine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Nunns, D.;Hawthorne, B.;Goulding, P.;Maresh, M.",1995,Sep,,0,0,
620,Treatment with D-penicillamine improves dopamine D2-receptor binding and T2-signal intensity in de novo Wilson's disease,"We report the results of in vivo striatal dopamine D2-receptor binding assessed by PET using 11C-raclopride (only one patient) and by single-photon emission computed tomography (SPECT) using 123I-iodobenzamide (123I-IBZM) and the findings of T2-weighted MRIs in two de novo Wilson's disease patients before and 4 months after initiation of D-penicillamine treatment. Before treatment, specific 11C-raclopride binding (only patient 1) was markedly reduced, with a putamen to cerebellum ratio of 1.99 (controls: 3.99 +/- 0.55, n = 15) and a caudate to cerebellum ratio of 2.52 (controls: 3.65 +/- 0.59, n = 15). Specific 123I-IBZM binding was reduced in both patients, with a basal ganglia to frontal cortex ratio of 1.25 (patient 1) and of 1.41 (patient 2) controls: 1.57 +/- 0.04, n = 5). After 4 months of therapy, 11C-raclopride-PET improved to a putamen to cerebellum ratio of 2.52 and a caudate to cerebellum ratio of 3.06 (patient 1). 123I-IBZM-SPECT revealed an increase of basal ganglia to frontal cortex ratios of 1.34 (patient 1) and 1.55 (patient 2). On heavily T2-weighted MRI sequences, hyperintense signal changes before therapy within the putamen (both patients), brainstem (only patient 1), and caudate (only patient 2) greatly diminished after treatment. Reduced striatal dopamine D2-receptor binding in these Wilson's disease patients improved under therapy, suggesting, in part, a reversible defect of striatal neurons.","Adolescent;Adult;Benzamides;Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Magnetic Resonance Imaging;Male;*Penicillamine/tu [Therapeutic Use];Pyrrolidines;Receptors, Dopamine D2/de [Drug Effects];*Receptors, Dopamine D2/me [Metabolism];Tomography, Emission-Computed, Single-Photon;0 (Benzamides);0 (Pyrrolidines);0 (Receptors, Dopamine D2);84226-06-2 (3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide);GNN1DV99GX (Penicillamine)","Schwarz, J.;Antonini, A.;Kraft, E.;Tatsch, K.;Vogl, T.;Kirsch, C. M.;Leenders, K. L.;Oertel, W. H.",1994,Jun,,0,0,
621,Initial and follow-up brain MRI findings and correlation with the clinical course in Wilson's disease,"We performed pretreatment brain MRIs in 25 patients with neurologically symptomatic Wilson's disease (WD) and clinical and MRI follow-up in 16 of them. All 25 pretreatment MRIs revealed abnormalities, with abnormal high-signal intensity (HSI) in bilateral thalami being the most common (92%). HSI lesions in the brainstem (84%) and the basal ganglia (72%) were also common. Brain atrophy was present in 88% of the 25 patients. In the follow-up period of 5 to 24 months, during which the patients were treated with D-penicillamine, both HSI lesions and neurologic symptoms improved in 88% of the 16 patients, but the brain atrophy did not change.",Adolescent;Adult;Atrophy;*Brain/pa [Pathology];Female;Follow-Up Studies;*Hepatolenticular Degeneration/di [Diagnosis];Humans;*Magnetic Resonance Imaging;Male,"Roh, J. K.;Lee, T. G.;Wie, B. A.;Lee, S. B.;Park, S. H.;Chang, K. H.",1994,Jun,,0,0,
622,Wilson's disease. Psychiatric manifestations may be the clinical presentation,"It is important to consider Wilson's disease in patients with psychiatric signs and symptoms who also have abnormal liver function test results or neurologic findings, or both. Thorough evaluation of emotionally disturbed persons, including complete history taking, careful physical examination, and appropriate laboratory profile, generally rules out or arouses suspicion of Wilson's disease during routine screening. Laboratory abnormalities necessitate repeated studies and additional family and personal history taking with emphasis on possible Wilson's disease. Further workup may then be indicated. Prompt recognition and vigorous, consistent treatment can minimize symptoms and tissue damage. Identifying a case of Wilson's disease and seeing clinical aspects improve with appropriate therapy is gratifying. [References: 14]","Clonazepam/tu [Therapeutic Use];Copper/bl [Blood];Copper/ur [Urine];Cornea/pa [Pathology];Diagnosis, Differential;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Liver Function Tests;Male;Medical History Taking;*Mental Disorders/et [Etiology];Middle Aged;Penicillamine/tu [Therapeutic Use];Physical Examination;5PE9FDE8GB (Clonazepam);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Jackson, G. H.;Meyer, A.;Lippmann, S.",1994,Jun,,0,0,
623,Treatment of Wilson's disease with zinc. XIII: Therapy with zinc in presymptomatic patients from the time of diagnosis,"The siblings of patients with newly diagnosed Wilson's disease are each at 25% risk of also having this autosomal recessive disease. Screening these siblings allows their detection and institution of prophylactic therapy before they become clinically ill. Herein we report the successful treatment of 13 presymptomatic patients with zinc acetate. These patients who received zinc have been followed for 3 to 9 years. In well-complying patients, 24-hour urine copper and non-ceruloplasmin plasma copper levels have decreased over years of follow-up, consistent with the elimination of the excess easily mobilized copper (the potentially toxic copper) of the body. Effect of therapy and compliance are easily monitored by following 24-hour urine zinc and copper levels. The urine copper level is a good reflection of the body's excess load of easily mobilizable copper. It will increase if control is not adequate. A decrease in urine zinc is an early signal that the patient's compliance is not optimal. The levels of hepatic copper in response to several years of zinc therapy may remain the same, go down, or go up temporarily. This is a reflection of zinc induction of hepatic metallothionein, which sequesters copper in a non-toxic pool. Hepatic copper levels should not be used to manage therapy. Liver function is well preserved by zinc therapy, and no zinc toxicity occurred in these 13 patients. No patient developed symptoms related to Wilson's disease. We conclude that zinc acetate is a fully effective and non-toxic therapy for the prophylactic treatment of the presymptomatic Wilson's disease patient.",Adolescent;Adult;Child;Copper/bl [Blood];Copper/ur [Urine];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Iron/bl [Blood];Lipids/bl [Blood];Liver/me [Metabolism];Liver Function Tests;Male;Metallothionein/me [Metabolism];Patient Compliance;*Zinc/tu [Therapeutic Use];Zinc/ur [Urine];0 (Lipids);789U1901C5 (Copper);9038-94-2 (Metallothionein);E1UOL152H7 (Iron);J41CSQ7QDS (Zinc),"Brewer, G. J.;Dick, R. D.;Yuzbasiyan-Gurkan, V.;Johnson, V.;Wang, Y.",1994,Jun,,0,0,
624,Treatment of Wilson's disease with ammonium tetrathiomolybdate. I. Initial therapy in 17 neurologically affected patients,"OBJECTIVE: To test the efficacy and toxicity of a new drug, ammonium tetrathiomolybdate, in the initial treatment of a relatively large series of patients presenting with neurologic signs and symptoms caused by Wilson's disease. The key aspect of efficacy was to preserve the neurologic function present at the onset of therapy. DESIGN: An open study of 17 patients treated for 8 weeks each. Neurologic function was evaluated by frequent quantitative neurologic and speech examinations. Several copper-related variables were studied to evaluate the effect of the drug on copper, and a large number of biochemical and clinical variables were studied to evaluate potential toxicity. Patients were then followed up at yearly intervals, with follow-up periods of 1 to 5 years reported. SETTING: A university hospital referral setting INTERVENTION: Patients were generally treated for 8 weeks with tetrathiomolybdate, followed by zinc maintenance therapy. MAIN OUTCOME MEASURES: Neurologic function was evaluated by quantitative neurologic and speech examinations. RESULTS: None of the patients suffered a loss of neurologic function. Copper status and potential further toxic effects were generally well controlled quickly. No toxic effects resulted from administration of tetrathiomolybdate. During the ensuing period of follow-up of 1 to 5 years, neurologic recovery in most patients was good to excellent. CONCLUSIONS: Tetrathiomolybdate appears to be an excellent form of initial treatment in patients with Wilson's disease presenting with neurologic signs and symptoms. In contrast to penicillamine therapy, initial treatment with tetrathiomolybdate does not result in further, often irreversible neurologic deterioration.",Adolescent;Adult;Copper/bl [Blood];Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Molybdenum/tu [Therapeutic Use];Nervous System Diseases/co [Complications];Trichloroacetic Acid/me [Metabolism];5V2JDO056X (Trichloroacetic Acid);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Brewer, G. J.;Dick, R. D.;Johnson, V.;Wang, Y.;Yuzbasiyan-Gurkan, V.;Kluin, K.;Fink, J. K.;Aisen, A.",1994,Jun,,0,0,
625,Penicillamine hypersensitivity: successful desensitization of a patient with severe hepatic Wilson's disease,"We report a 16-yr-old patient who developed a severe allergic reaction to penicillamine which was prescribed for newly diagnosed hepatic Wilson's disease. The patient's name was placed on the liver transplant waiting list because of the severity of her liver disease. We describe successful desensitization to penicillamine, so that medical therapy alone was sufficient for management of her condition.",Adolescent;Drug Hypersensitivity/et [Etiology];*Drug Hypersensitivity/th [Therapy];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Transplantation;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Prednisone/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);VB0R961HZT (Prednisone),"Chan, C. Y.;Baker, A. L.",1994,Mar,,0,0,
626,Nontransplant options for the treatment of metabolic liver disease: saving livers while saving lives,,Genetic Therapy;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Humans;*Liver Diseases/th [Therapy];Liver Transplantation;*Metabolic Diseases/th [Therapy];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Balistreri, W. F.",1994,Mar,,0,0,
627,Wilson's disease: varied hepatic presentations,"BACKGROUND: Wilson's disease is an inherited disorder of copper metabolism. Previous Indian studies have high-lighted the neurological manifestations of this disorder. Eleven patients with Wilson's disease with different hepatic manifestations are reported. METHODS: Patients referred to the gastroenterology department of a tertiary referral center were investigated for Wilson's disease, based on clinical suspicion, with slit-lamp examination for Kayser-Fleischer rings, serum ceruloplasmin and 24-hour urinary copper estimation. Liver biopsy was done whenever possible. RESULTS: Patients with Wilson's disease presented as acute viral hepatitis (n = 5), fulminant hepatic failure (n = 2), subacute hepatic failure (n = 2) and cryptogenic cirrhosis (n = 2). Therapy with penicillamine/trientene and zinc sulphate was started in 9 patients; 5 showed good response to therapy, one had to be switched to trientene due to penicillamine toxicity, two died, and one was lost to follow-up. CONCLUSION: Wilson's disease has varied hepatic presentations and should be suspected in all patients with unexplained liver disease. Any young adult presenting with acute hepatitis or fulminant hepatic failure who has evidence of underlying chronic liver disease or associated hemolytic anemia should be investigated for Wilson's disease. Therapy with penicillamine or trientene combined with zinc sulphate shows improvement in a majority of patients.",Adolescent;Adult;Child;Female;*Hepatolenticular Degeneration/di [Diagnosis];Humans;Male,"Gill, H. H.;Shankaran, K.;Desai, H. G.",1994,Jul,,0,1,
628,"Wilson's disease--a review of cases at University Hospital, Kuala Lumpur","The clinical course of 18 patients with Wilson's disease is reported. There were 13 males and five females of whom one is Malay. The prevalence of Wilson's disease in Malaysia is probably the same as elsewhere. Being a genetic syndrome, the genetic carrier rate for Wilson's disease is probably lower amongst the Malays. At diagnosis, the clinical signs were predominantly hepatic in 10 patients, neurological in five patients with three asymptomatic cases. All patients were commenced on penicillamine but poor compliance was observed in many patients. Two patients defaulted follow-up and seven patients died. Out of the nine surviving patients, only four are well with no clinical symptoms.","Adolescent;Adult;Child;Consanguinity;Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/ge [Genetics];Heterozygote;Hospitals, University;Humans;Malaysia/ep [Epidemiology];Male;Penicillamine/tu [Therapeutic Use];*Population Surveillance;Prevalence;Survival Rate;Treatment Outcome;Treatment Refusal;GNN1DV99GX (Penicillamine)","Mohamed, R.;Tan, C. T.;Wong, N. W.",1994,Mar,,0,0,
629,D-penicillamine-induced elastosis perforans serpiginosa and localized cutis laxa in a patient with Wilson's disease,A patient with Wilson's disease who developed elastosis perforans serpiginosa and localized cutis laxa during prolonged treatment with D-penicillamine is described. Induction of elastosis perforans serpiginosa and of cutis laxa by D-penicillamine may be due to a similar mechanism.,Child;Connective Tissue Diseases/co [Complications];*Cutis Laxa/co [Complications];*Elastic Tissue/de [Drug Effects];Female;*Hepatolenticular Degeneration/co [Complications];Humans;*Penicillamine/ae [Adverse Effects];Skin Diseases/ci [Chemically Induced];*Skin Diseases/co [Complications];GNN1DV99GX (Penicillamine),"Amichai, B.;Rotem, A.;Metzker, A.",1994,Aug,,0,0,
630,The diagnostic value of multi-modality evoked potentials in Wilson's disease,"19 patients with a neurological manifestation of Wilson's disease (WD), most of them with long-term disease (> 10 yr), underwent clinical, psychometrical and electrophysiological evaluation in order to test whether there is a correlation of psychometrical and evoked potential (EP) abnormalities with a semiquantitative clinical score ranging from no (0) to severe (3) symptoms. The following EPs were recorded: acoustically evoked event-related (ERPs), somato-sensory (SSEPs), visually (VEPs) and brainstem evoked potentials (BSEPs). Results were compared with the data of an age- and sex-matched control group. 89% of the patients revealed clinical signs of basal ganglia dysfunction, 11% oculomotor or cerebellar symptoms, but none of the individuals had any clinical hint for visual pathway affection. Psychometrically, 100% had mood disturbances without definite intellectual decline. In EP-recordings, 100% showed ERP, 58.0% SSEP and 53% VEP and BSEP abnormalities. VEP and BSEP measurements did not correlate with the clinical score. There was only a weak correlation of SSEP (right-side)- and ERP-amplitude reduction with the clinical total score. The only significant correlation was found between the clinical total score and the time dependent psychometrical tests. Thus, there is a fairly high percentage of subclinical cerebral impairment in Wilson patients with long-term disease detectable by ERP-recordings which do, however, not correlate with the clinical status of the patients.","Adult;Attention;Case-Control Studies;*Evoked Potentials/ph [Physiology];Evoked Potentials, Auditory/ph [Physiology];Evoked Potentials, Auditory, Brain Stem/ph [Physiology];Evoked Potentials, Somatosensory/ph [Physiology];Evoked Potentials, Visual/ph [Physiology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/px [Psychology];Humans;Intelligence;Male;Memory, Short-Term;Mental Disorders/di [Diagnosis];Penicillamine/tu [Therapeutic Use];Reaction Time/ph [Physiology];GNN1DV99GX (Penicillamine)","Arendt, G.;Hefter, H.;Stremmel, W.;Strohmeyer, G.",1994,Apr-May,,0,0,
631,Penicillamine-induced elastosis perforans serpiginosa treated successfully with isotretinoin,"Elastosis perforans serpiginosa (EPS) and the elastotic changes of pseudoxanthoma elasticum (PXE) are rare but well-recognized side-effects of long-term penicillamine therapy. A 42-year old female patient who developed both of these cutaneous side-effects following treatment with high-dose penicillamine for Wilson's disease is described; near-complete resolution of the EPS, but not the PXE was achieved by treatment with isotretinoin (0.5 mg/kg/day) for 6 weeks, despite continuation of the penicillamine.",Adult;Elastic Tissue/pa [Pathology];*Elastic Tissue;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Isotretinoin/tu [Therapeutic Use];*Penicillamine/ae [Adverse Effects];Pseudoxanthoma Elasticum/ci [Chemically Induced];Pseudoxanthoma Elasticum/dt [Drug Therapy];*Skin Diseases/ci [Chemically Induced];*Skin Diseases/dt [Drug Therapy];EH28UP18IF (Isotretinoin);GNN1DV99GX (Penicillamine),"Ratnavel, R. C.;Norris, P. G.",1994,,,0,0,
632,Copper associated childhood cirrhosis,"Several papers have reported severe liver disease in association with massive hepatic copper accumulation, which do not seem to be either of the recognised copper associated liver diseases, namely Wilson's disease and Indian childhood cirrhosis. A further case is reported in which novel copper kinetic studies were carried out using the stable isotope 65Cu, showing that this patient did not suffer from Wilson's disease. It is suggested that these cases can be divided into two groups on the basis of age, clinical course, and history of excessive copper ingestion. The benefits of using 65Cu for in vivo studies of copper metabolism is discussed.","Bangladesh/eh [Ethnology];Child, Preschool;*Copper/me [Metabolism];Humans;Isotopes;Liver/pa [Pathology];Liver Cirrhosis/dt [Drug Therapy];*Liver Cirrhosis/et [Etiology];Liver Cirrhosis/me [Metabolism];Liver Cirrhosis/pa [Pathology];Male;Penicillamine/tu [Therapeutic Use];United Kingdom;0 (Isotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Horslen, S. P.;Tanner, M. S.;Lyon, T. D.;Fell, G. S.;Lowry, M. F.",1994,Oct,,0,0,
633,Dangers of interrupting decoppering treatment in Wilson's disease,,Adult;Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Penicillamine/ad [Administration & Dosage];*Sulfates/ad [Administration & Dosage];*Zinc Compounds/ad [Administration & Dosage];Zinc Sulfate;0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Hoogenraad, T. U.",1994,Oct,,0,0,
634,Wilson's disease: neurological and magnetic resonance imaging improvement on zinc treatment,,Adult;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;*Sulfates/tu [Therapeutic Use];*Zinc Compounds/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate),"Heckmann, J. M.;Eastman, R. W.;De Villiers, J. C.;Hewlett, R.",1994,Oct,,0,0,
635,Wilson's disease: unusual clinical and radiological features,,"Adolescent;Brain/dg [Diagnostic Imaging];*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Knee Joint/dg [Diagnostic Imaging];Male;Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Garg, R. K.;Kar, A. M.;Agrawal, A.;Agrawal, S.;Agrawal, V.",1994,Mar,,0,0,
636,Penicillamine as antioxidant,,"Animals;*Antioxidants/pd [Pharmacology];Copper/bl [Blood];*Copper/pd [Pharmacology];Copper/to [Toxicity];Erythrocyte Membrane/de [Drug Effects];*Erythrocyte Membrane/me [Metabolism];Free Radicals;Hepatolenticular Degeneration/bl [Blood];Humans;Male;*Penicillamine/pd [Pharmacology];Rats;Rats, Wistar;0 (Antioxidants);0 (Free Radicals);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Miki, M.",1994,,,0,0,
637,Treatment of Wilson's disease with zinc XII: dose regimen requirements,"A considerable body of data is now available indicating the efficacy and lack of toxicity of zinc treatment of Wilson's disease. Dose-response studies have shown that regimens of 50 mg of elemental zinc 3 times a day (50 mg x 3), 25 mg x 3, and 50 mg x 2 are effective, but 25 mg x 2 and 50 mg x 1 are not adequately effective. These studies indicate that 75 mg a day is close to the minimally effective dose, but do not address the question of necessary dose frequency. In the current study, the authors have used the minimally effective daily dose, 75 mg, and studied this daily dose in regimens of 25 mg x 3, 37.5 mg x 2, and 75 mg x 1 in treatment of four patients with Wilson's disease. These data have been supplemented with additional data from 11 patients treated with 25 mg 3 times a day and with data from 2 patients treated with 75 mg once a day. Efficacy was evaluated by 10-day copper balance and absorption of orally administered 64copper. The findings indicate that a daily dose of 75 mg must be divided into at least two doses to be effective, and that the 64copper procedure is more sensitive to zinc dose than copper balance.",Copper/me [Metabolism];Drug Administration Schedule;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;*Zinc/ad [Administration & Dosage];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Johnson, V.;Dick, R. D.;Wang, Y.",1993,Apr,,0,0,
638,Molecular genetics and zinc-copper interactions in human Wilson's disease and canine copper toxicosis,,Animals;Copper/me [Metabolism];*Copper/po [Poisoning];*Dog Diseases/dt [Drug Therapy];Dog Diseases/ge [Genetics];Dogs;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Pregnancy;Pregnancy Complications/dt [Drug Therapy];Zinc/ae [Adverse Effects];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Lee, D. Y.",1993,,,0,0,
639,Penicillamine-induced changes in elastic tissue of the upper respiratory tract,"We describe a patient who developed upper respiratory tract symptoms following long-term treatment of Wilson's disease with penicillamine. These symptoms were attributed to areas of pharyngeal thickening and were treated with a laser. Histological examination of the lesions showed proliferations of abnormal elastic fibres similar to those previously described at other sites, especially the skin, in patients receiving penicillamine. This drug impairs the maturation and reduces the stability of elastic fibres and although elastic tissue throughout the body is affected, we are aware of no previous reports of penicillamine-induced changes presenting with upper respiratory tract symptoms.",Back;*Elastic Tissue/de [Drug Effects];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;Neck;*Penicillamine/ae [Adverse Effects];*Respiratory System/de [Drug Effects];*Skin/de [Drug Effects];Time Factors;GNN1DV99GX (Penicillamine),"Manohar, M. B.;Boldy, D. A.;Bryan, R. L.;Pearman, K.",1993,Jan,,0,0,
640,"Motor impairment in Wilson's disease, II: Slowness of speech","The maximal syllable production rate (MSPR) and the ability to reproduce a given target frequency in the 1 to 8 Hz range by repeating the short syllable ""ta"" was tested in 20 patients with Wilson's disease (WD) and 20 normal subjects. MSPR was significantly reduced in the WD-patients. In the 1 to 5 Hz range normal subjects as well as WD-patients tended to produce slightly higher frequencies than the target frequencies. This hastening was maximal in normals between 4 to 5 Hz whereas in the WD-patients hastening mainly occurred between 3 to 4 Hz. The test results showed a considerable variation across the patients. This variation can be interpreted on the basis of the theory of coupled oscillators. Comparison of speech and finger movements revealed a highly significant correlation between MSPR and the highest possible frequency of voluntary alternating index finger movements. As an application of the presented test treatment effects on speech movements were demonstrated.","Adolescent;Adult;Basal Ganglia/de [Drug Effects];Basal Ganglia/pp [Physiopathology];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver Transplantation/ph [Physiology];Male;Microcomputers;Middle Aged;Muscle Contraction/de [Drug Effects];*Muscle Contraction/ph [Physiology];Neurologic Examination;Penicillamine/tu [Therapeutic Use];Reaction Time/de [Drug Effects];*Reaction Time/ph [Physiology];Signal Processing, Computer-Assisted/is [Instrumentation];Sound Spectrography/is [Instrumentation];Speech Production Measurement;Verbal Behavior/de [Drug Effects];*Verbal Behavior/ph [Physiology];GNN1DV99GX (Penicillamine)","Hefter, H.;Arendt, G.;Stremmel, W.;Freund, H. J.",1993,Feb,,0,0,
641,"Motor impairment in Wilson's disease, I: Slowness of voluntary limb movements","Twenty-three patients with Wilson's disease (WD) treated with D-penicillamine underwent clinical examination, as well as laboratory and motor testing. The clinical findings were scored. Laboratory tests included determination of the caeruloplasmin level, the free serum copper level, 24 h urinary copper excretion, liver enzymes and in 10 patients liver copper content of a liver biopsy. Laboratory tests and clinical scores were correlated. To quantify impairment of voluntary movements in WD fastest possible isometric index finger extensions and fastest alternating finger movements were analysed. Eleven patients presented with abnormally slow and 15 with abnormally irregular voluntary movements. Slowness of alternating movements correlated with the clinical score. The clinical score also correlated with the duration of symptoms prior to onset of therapy. Motor testing turned out to be sensitive enough to monitor improvement of neurological symptoms after onset of therapy. Comparison with motor testing in other basal ganglia diseases and cerebellar patients showed differences to patients with Parkinson's and Huntington's disease and similarities to patients suffering from AIDS-related dementia. In a small number of WD-patients similar results as in patients with a degenerative cerebellar disease were found.",Adolescent;Adult;Basal Ganglia/de [Drug Effects];Basal Ganglia/pp [Physiopathology];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Isometric Contraction/de [Drug Effects];Isometric Contraction/ph [Physiology];Liver Function Tests;Liver Transplantation/ph [Physiology];Male;Middle Aged;Muscle Contraction/de [Drug Effects];*Muscle Contraction/ph [Physiology];Neurologic Examination/de [Drug Effects];Penicillamine/tu [Therapeutic Use];Postoperative Complications/di [Diagnosis];Postoperative Complications/pp [Physiopathology];Reaction Time/de [Drug Effects];*Reaction Time/ph [Physiology];GNN1DV99GX (Penicillamine),"Hefter, H.;Arendt, G.;Stremmel, W.;Freund, H. J.",1993,Feb,,0,0,
642,Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents,"Zinc (Zn) is increasingly being used as a treatment for Wilson's disease. Some physicians have been prescribing Zn in conjunction with other anticopper agents, such as penicillamine or trien, although theoretically these drugs might be antagonistic in their effects. In addition, Wilson's disease patients quite often take vitamin C in high doses in conjunction with Zn therapy, and there are indications of possible interactions among vitamin C, Zn and copper (Cu). Interactions of penicillamine, trien, and vitamin C with Zn have not been previously studied in terms of the potential effects of these agents on Zn efficacy in Wilson's disease. Here we have studied these interactions in the maintenance phase of therapy, using Cu balance and absorption of orally administered 64Cu as endpoints. We find evidence for probable interactions of both penicillamine and trien with Zn; however, the end result on Cu balance is about the same with Zn alone as it is with Zn plus one of the other agents. Thus, there appear to be no advantages to concomitant administration. We find no detectable interaction of Zn and vitamin C on Cu balance, when vitamin C is taken in daily doses of 1000 mg.","Ascorbic Acid/pd [Pharmacology];Copper/ad [Administration & Dosage];*Copper/pk [Pharmacokinetics];Copper Radioisotopes;Drug Interactions;Drug Therapy, Combination;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Penicillamine/pd [Pharmacology];Trientine/pd [Pharmacology];*Zinc/pd [Pharmacology];Zinc/tu [Therapeutic Use];0 (Copper Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);PQ6CK8PD0R (Ascorbic Acid);SJ76Y07H5F (Trientine)","Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Johnson, V.;Dick, R. D.;Wang, Y.",1993,Feb,,0,0,
643,Acquired sideroblastic anaemia during treatment of Wilson's disease with triethylene tetramine dihydrochloride,"We report one case of acquired sideroblastic anaemia in a patient treated for Wilson's disease with triethylene tetramine dihydrochloride (TTH). No other cause of acquired sideroblastic anaemia was found, and neither iron nor pyridoxine therapy could correct this anaemia. In contrast, decreasing the dose of TTH led to disappearance of ringed sideroblasts. Thus TTH should be added as a further cause of secondary acquired sideroblastic anaemia. The pathophysiology of this finding, probably linked to an abnormality of mitochondrial iron metabolism, is briefly discussed.","Adolescent;*Anemia, Sideroblastic/ci [Chemically Induced];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Trientine/ae [Adverse Effects];SJ76Y07H5F (Trientine)","Condamine, L.;Hermine, O.;Alvin, P.;Levine, M.;Rey, C.;Courtecuisse, V.",1993,Jan,,0,0,
644,Geographic variations in Wilson's disease,"Certain features of Wilson's disease (WD) in Asia have been found to be different from those in other continents. The higher prevalence rate in Japan is presumably due to a higher consanguinity rate. In Chinese there is a tight linkage between WD and two gene loci for esterase D and retinoblastoma in the long arm of chromosome 13. The high proportion of patients with hepatic presentation accounts for early onset of WD in the Japanese and Chinese series. Skeletal involvement, leg hyperpigmentation, dark complexion, amenorrhea, epileptic seizures, and cerebral white matter degeneration are relatively more common among WD patients in Asia. Excessive copper in the liver appears to have a protective effect against hepatocellular carcinoma and type B hepatitis. Electrophysiological studies suggest widespread functional disturbances of the CNS in WD. Side-effects from penicillamine are rather frequent and often lead to interruption of the therapy. Trien is found to be effective without adverse reactions. Oral zinc therapy may be a suitable alternative for long-term management of WD patients in developing Asian countries. [References: 77]","Adolescent;Adult;Brain Diseases, Metabolic/et [Etiology];Brain Diseases, Metabolic/pp [Physiopathology];Carcinoma, Hepatocellular/ep [Epidemiology];China/ep [Epidemiology];Comorbidity;Consanguinity;Copper/me [Metabolism];Disease Susceptibility;Electroencephalography;Ethnic Groups/ge [Genetics];Europe/ep [Epidemiology];Female;Gene Frequency;Genes, Recessive;Hepatitis B/ep [Epidemiology];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/eh [Ethnology];Hepatolenticular Degeneration/ge [Genetics];Humans;Incidence;India/ep [Epidemiology];Japan/ep [Epidemiology];Liver Neoplasms/ep [Epidemiology];Male;Penicillamine/tu [Therapeutic Use];Phenotype;Pregnancy;Pregnancy Complications/dt [Drug Therapy];Prevalence;Socioeconomic Factors;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Chu, N. S.;Hung, T. P.",1993,Jul,,0,1,
645,Chelation treatment of neurological Wilson's disease,"The results of chelation treatment of 137 patients presenting with neurological Wilson's disease are described, together with the more commonly observed toxic reactions to the various drugs employed. Fifty-seven patients made an excellent response to treatment and became symptom free. Thirty-six patients made a good recovery, but were left with some minor neurological deficit. Twenty-four patients had a poor response: although the disease process was arrested they were left more or less disabled. Twenty patients died: nine had little or no treatment, but 11 died despite apparently adequate chelation therapy. There was no obvious reason for this failure. The liver copper level was estimated in six of these patients: it was still significantly elevated in only one, but in all four in whom it was possible to make the determination, the concentration of copper in the basal ganglia was in excess of 45 micrograms/g wet weight. It was not apparent why adequate therapy failed to remove copper from the brains of these patients. There was no obvious clinical, histological or biochemical indicator of failure to respond to treatment. Initial deterioration before improvement was seen in 30 patients: the prognosis for a useful recovery was not necessarily worse than that in patients who did not show this phenomenon.",Adolescent;Adult;Cause of Death;*Chelation Therapy;*Copper;Drug Administration Schedule;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/mo [Mortality];Humans;Male;Middle Aged;Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Time Factors;Treatment Outcome;*Trientine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Walshe, J. M.;Yealland, M.",1993,Mar,,0,1,
646,Neurological Wilson's disease,,Child;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"McIntyre, N.",1993,May,,0,0,
647,"Hypercalciuria and nephrocalcinosis, a feature of Wilson's disease",Hypercalciuria and nephrocalcinosis are not uncommon in patients with Wilson's disease but have only once been reported as the presenting sign. We diagnosed Wilson's disease in a 17-year-old male patient 6 years after his first episode of gross hematuria and 2 years after detection of hypercalciuria and nephrocalcinosis. Therapy with penicillamine resulted only in a moderate reduction of urinary calcium excretion but oxalate excretion increased.,Adolescent;*Calcium/ur [Urine];Hematuria/di [Diagnosis];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ur [Urine];Humans;Kidney Calculi/di [Diagnosis];Male;*Nephrocalcinosis/di [Diagnosis];Nephrocalcinosis/dg [Diagnostic Imaging];Nephrocalcinosis/dt [Drug Therapy];Oxalates/ur [Urine];Oxalic Acid;Penicillamine/tu [Therapeutic Use];Time Factors;Ultrasonography;0 (Oxalates);9E7R5L6H31 (Oxalic Acid);GNN1DV99GX (Penicillamine);SY7Q814VUP (Calcium),"Hoppe, B.;Neuhaus, T.;Superti-Furga, A.;Forster, I.;Leumann, E.",1993,,,0,0,
648,Does a vegetarian diet control Wilson's disease?,"The literature indicates that copper (Cu) is less bioavailable from a vegetarian as compared to mixed diet. Further, several groups, including ours, find rather marginal average Cu intake in the typical American diet. For example, our data indicate that Wilson's disease patients on a typical American diet ingest only about 25% more Cu than is required. This suggests that a vegetarian diet, if it reduced bioavailability by about 25% or more, would be an adequate maintenance therapy for Wilson's disease. Observations in two of our patients, who were on lactovegetarian diets by choice, and who were almost totally noncompliant with anti-Cu therapy, support this view. These observations suggest that vegetarian diets may be a management tool for Wilson's disease. They also further emphasize the marginal Cu intake in American diets, and suggest that some seemingly healthy people, particularly vegetarians, may be at risk for mild Cu deficiency.","Acetates/pk [Pharmacokinetics];Acetates/tu [Therapeutic Use];Acetic Acid;Adult;Biological Availability;Ceruloplasmin/an [Analysis];Copper/an [Analysis];Copper/pk [Pharmacokinetics];*Diet, Vegetarian;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dh [Diet Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/me [Metabolism];Zinc/ur [Urine];0 (Acetates);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);J41CSQ7QDS (Zinc);Q40Q9N063P (Acetic Acid)","Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Dick, R.;Wang, Y.;Johnson, V.",1993,Oct,,0,0,
649,Hemolytic episode in a patient with Wilson's disease treated with zinc,,"Adult;*Anemia, Hemolytic/et [Etiology];Anemia, Hemolytic/me [Metabolism];Copper/me [Metabolism];Female;Hemolysis/de [Drug Effects];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];*Sulfates/tu [Therapeutic Use];*Zinc Compounds/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Shimon, I.;Moses, B.;Sela, B. A.;Dolev, E.",1993,Oct,,0,0,
650,Wilson disease,,Ceruloplasmin/an [Analysis];Copper/an [Analysis];Copper/bl [Blood];Copper/ur [Urine];Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/et [Etiology];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];Hepatolenticular Degeneration/ur [Urine];*Hepatolenticular Degeneration;Humans;Liver/ch [Chemistry];Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Sulfates/pd [Pharmacology];Sulfates/tu [Therapeutic Use];Zinc Compounds/pd [Pharmacology];Zinc Compounds/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);0 (Zinc Compounds);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Houwen, R. H.;van Hattum, J.;Hoogenraad, T. U.",1993,Aug,,0,0,
651,Wilson's disease: a diagnosis made in two individuals greater than 40 years of age,"Wilson's disease is an autosomal recessive disease of copper metabolism which is widely recognized as a disease occurring clinically in children, adolescents, and young adults. Unrecognized and therefore untreated Wilson's disease in patients over age 40 is thought to occur either rarely or not at all. Two cases of Wilson's disease presenting at an age greater than 40 years are presented. The first is a 42-year-old Israeli women who presented with fulminant hepatic failure. The serologic and biochemical investigations obtained at the time of her fulminant hepatic failure included copper studies which suggested the diagnosis of Wilson's disease, which was confirmed by an examination of the native liver following successful orthotopic liver transplantation. The second case is that of a 56-year-old white male who presented to the hospital with a three-year history of neurological dysfunction, pancytopenia, and mild splenomegaly. A battery of serologic and biochemical investigations suggested a diagnosis of Wilson's disease. The diagnosis was confirmed by quantitative hepatic copper estimation and the demonstration of Wilson's disease in three of his siblings, all of whom were diagnosed after the proband case had been identified. This man and his siblings have been treated with d-penicillamine, with remarkable improvement in their neurologic and hepatic function. The proband is currently well 11 years after his diagnosis was established. These two cases demonstrate that a diagnosis of Wilson's disease should be considered as part of the differential diagnosis of individuals in the fourth and fifth decades of life who present with unexplained liver disease.",Adult;Age Factors;Female;*Hepatolenticular Degeneration/di [Diagnosis];Humans;Male;Middle Aged,"Bellary, S. V.;Van Thiel, D. H.",1993,Sep,,0,0,
652,Fate of orally administered triethylenetetramine dihydrochloride: a therapeutic drug for Wilson's disease,"Triethylenetetramine dihydrochloride (TETA) is a therapeutic drug for Wilson's disease. We developed a simple fluorometric method for detection of TETA in biological fluids by using high-performance liquid chromatography (HPLC), and examined TETA concentrations in the serum and urine of two healthy adults who were given TETA orally. No TETA peak was detected in the serum. The amount of TETA in the urine of the two adults was only 1.6 and 1.7% of the dose administered. However, a large unidentified peak appeared in the urine after oral administration. This peak was not observed in a mixture of TETA and control urine or in urine before TETA administration. When the urine after TETA administration was analyzed after hydrolysis with HCl, the unidentified peak disappeared, while the TETA peak increased. These findings indicate that the substance which yielded the unidentified peak is a metabolite of TETA, suggesting that most of the TETA administered is metabolized and then excreted in the urine.","Adult;Chromatography, High Pressure Liquid;Copper/ch [Chemistry];*Hepatolenticular Degeneration/me [Metabolism];Humans;Hydrolysis;Spectrometry, Fluorescence;Trichloroacetic Acid;Trientine/bl [Blood];*Trientine/pk [Pharmacokinetics];Trientine/ur [Urine];5V2JDO056X (Trichloroacetic Acid);789U1901C5 (Copper);SJ76Y07H5F (Trientine)","Kodama, H.;Meguro, Y.;Tsunakawa, A.;Nakazato, Y.;Abe, T.;Murakita, H.",1993,Jan,,0,0,
653,Urinary copper excretion after penicillamine in the diagnosis of Wilson's disease in children,,Child;*Copper/ur [Urine];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ur [Urine];Humans;*Penicillamine;Predictive Value of Tests;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Gregorio, G. V.;Mieli-Vergani, G.;Mowat, A. P.",1993,Nov,,0,0,
654,Hepatic manifestations of Wilson's disease: frequency and pattern in Saudi patients,"Seven symptomatic patients with Wilson's disease have so far been diagnosed at King Khalid University Hospital (KKUH), Riyadh, over the last six years. On family screening, another three asymptomatic patients were found to be affected. Five of the symptomatic patients had clinical features of liver disease on initial presentation and was preceded by renal dysfunction in another patient. The remaining patient presented with neurological features. Six patients had Kayser-Fleisher ring. Abnormal liver function tests were found in half of the patients. Ceruloplasmin was reduced in 7 of 10 patients. Serum copper and urinary copper estimations were most useful diagnostic laboratory tests. Morphological alteration was found in all 9 patients who had a percutaneous liver biopsy. All patients were treated initially with D-penicillamine and clinical response was noted in seven, of whom one developed neurological manifestations while receiving the treatment. D-penicillamine was replaced by zinc sulfate in 3 patients who developed thrombocytopenia. The data suggest that Wilson's disease may not be rare in Saudi Arabia. For early detection and prompt treatment, the disease should be suspected under appropriate clinical circumstances especially in young patients with liver diseases. Close relatives of such index patients should be routinely screened.",Adolescent;Adult;Child;Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/ep [Epidemiology];Humans;*Liver Diseases/co [Complications];Male;Saudi Arabia/ep [Epidemiology],"al Mofleh, I. A.;al Rashed, R. S.;Ayoola, E. A.;Sabah, D. M.;Hafeez, M. A.",1993,Jul-Sep,,0,0,
655,Wilson's disease: magnetic resonance imaging (MRI) with clinical correlations in 16 cases,"The purpose of this study was to evaluate MRI findings in a group of patients with Wilson's disease, trying to establish possible correlations between clinical and image data. Sixteen patients (8 males and 8 females), with ages ranging from 11 to 50 years, and duration of illness ranging from 5 months to 32 years, were submitted to MRI in a 1.5T System. Four patients were asymptomatic, 4 had mild neurological findings, 2 were moderately affected and the remaining 6 had a severe form of the disease. All patients were receiving D-penicillamine by the time of the study. The most symptomatic patients presented five or more sites of abnormalities on MRI. The putamen was affected in all symptomatic individuals and one asymptomatic and 11 of them presented dystonia on neurological examination. A striking feature was the peripheral localization of putaminal hyperintense lesions on T2 weighted images. In eight cases, striatum or ""substantia nigra"" lesions explained parkinsonism observed on neurological examination. MRI seems to be an efficient method to study neurological involvement of Wilson's disease allowing some interesting anatomo-clinical correlations.",Adolescent;Adult;*Brain/pa [Pathology];Child;Female;*Hepatolenticular Degeneration/pa [Pathology];Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Barbosa, E. R.;Caramelli, P.;Bacheschi, L. A.;Haddad, M. S.;Magalhaes, A. C.;Menezes, J. R.;Scaff, M.;Canelas, H. M.",1993,May-Jun,,0,0,
656,Wilson disease--penicillamine therapy and late presentation,,*Drug Monitoring;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Skeen, M. B.",1992,Mar 01,,0,0,
657,Wilson disease,"Wilson disease is an inherited disorder of copper metabolism. Progress has been made in establishing the location of the gene on the long arm of chromosome 13, and in finding nearby probes that can be used to identify affected sibs of newly diagnosed patients. However, the gene has not been cloned, and the molecular nature of the defect remains unknown. The cause of the disease is a failure to excrete unneeded and excessive copper in the bile for loss in the stool. This may be due to a failure to excrete copper packaged in ceruloplasmin into the bile. Clinically, patients usually present during the second to fourth decades of life with liver, neurologic, or psychiatric disease, but the diagnosis is often missed or delayed. Once a diagnosis of Wilson disease is considered, reliable studies of copper variables can be carried out. After diagnosis, patients must receive anticopper treatment for the rest of their lives, to reduce copper levels and prevent copper reaccumulation. For life-long maintenance therapy, we recommend zinc acetate because of its complete efficacy and lack of toxicity; it acts by blocking copper absorption. For initial therapy of the acutely ill patient, no currently available therapy has proven to be ideal. A chelator-type drug, either penicillamine or trien, can be used for the initial therapy of patients who present with liver disease; transition to zinc acetate can then be made after a few months. For the initial therapy of acutely ill patients who present with neurologic disease, chelation should be avoided because neurologic worsening frequently occurs, probably due to redistribution of copper which temporarily raises the levels of copper in the brain. For initial treatment, zinc therapy is also not ideal because it is relatively slow-acting. A new experimental drug, tetrathiomolybdate, shows promise in the initial treatment of patients with Wilson disease. The major challenges ahead include closing the remaining therapeutic hiatuses, cloning and expressing the gene to understand its function, and improving clinical diagnosis so that therapy can be instituted as quickly as possible. [References: 146]",Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans,"Brewer, G. J.;Yuzbasiyan-Gurkan, V.",1992,May,,0,0,
658,Penicillamine hepatotoxicity in the treatment of Wilson's disease,,"Child;Child, Preschool;Copper/bl [Blood];Copper/ur [Urine];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver/de [Drug Effects];Liver/me [Metabolism];Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Sulfates/tu [Therapeutic Use];Transaminases/an [Analysis];Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 2-6-1 (Transaminases);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Menara, M.;Zancan, L.;Sturniolo, G. C.",1992,Apr,,0,0,
659,Strategies for the development of new antiarthritic agents,"Therapeutic advances in rheumatoid arthritis (RA) have largely focused on the development of non-steroidal antiinflammatory drugs (NSAIDs) with improved characteristics compared with aspirin [Brooks & Day, New Engl. J. Med., 324, 1716-1725 (1991)]. For example, greater potency, safety, improved tolerance in the elderly and reduced frequency of dosing have been achieved. However, these agents are generally considered to be palliative treating of the symptoms of the disease. The development of disease modifying drugs (DMD), also known as second line drugs, for RA has not been very successful. Most of the agents that are currently used in this category were originally used to treat other diseases such as malignancy (cyclophosphamide, methotrexate), Wilson's disease (d-penicillamine) and tuberculosis (gold salts) [Pullar, Br. J. clin. Pharmac., 30, 501-510 (1990)]. Unfortunately, none of the agents is ideal and each has potentially serious side-effects. There have been several attempts to develop agents with new mechanisms of action that hopefully will greatly improve these current therapies. [References: 47]","*Anti-Inflammatory Agents, Non-Steroidal/tu [Therapeutic Use];*Arthritis, Rheumatoid/dt [Drug Therapy];Cell Adhesion Molecules/ph [Physiology];Cytokines/ai [Antagonists & Inhibitors];Humans;*Immunosuppressive Agents/tu [Therapeutic Use];Metalloendopeptidases/ai [Antagonists & Inhibitors];0 (Anti-Inflammatory Agents, Non-Steroidal);0 (Cell Adhesion Molecules);0 (Cytokines);0 (Immunosuppressive Agents);EC 3-4-24 (Metalloendopeptidases)","Lewis, A. J.;Glaser, K. B.;Sturm, R. J.;Molnar-Kimber, K. L.;Bansbach, C. C.",1992,Apr,,0,0,
660,Wilson's disease: current status,"OBJECTIVE: To review current concepts about the pathogenesis, clinical manifestations, and treatment of Wilson's disease, with an emphasis on recent developments. DATA IDENTIFICATION: Published information was identified using MEDLINE and through extensive manual searching of bibliographies in identified sources. RESULTS: The basic biochemical alteration responsible for deranged hepatobiliary copper homeostasis in Wilson's disease has yet to be identified. The gene for Wilson's disease has been mapped to chromosome 13, but the function of its gene product has not yet been determined. The clinical manifestations of Wilson's disease are varied and often nonspecific and include a range of hepatic, neurologic, and psychiatric findings. Penicillamine remains the drug of choice for the treatment of Wilson's disease, but recent experience suggests that trientine and zinc may be safe, effective alternatives. All three drugs are probably safe for use in pregnant patients with Wilson's disease. Liver transplantation is the only effective treatment for Wilsonian fulminant hepatic failure and corrects the underlying metabolic defect. CONCLUSIONS: Wilson's disease is a disorder of hepatobiliary copper excretion manifested predominantly by hepatic and neurologic copper toxicosis and inherited in an autosomal recessive pattern. Although the specific underlying biochemical defect remains to be defined, specific therapy is available and usually successful. Maintaining a high index of suspicion is critical in diagnosing this readily treatable inherited disease. [References: 167]","Administration, Oral;Ceruloplasmin/an [Analysis];Copper/an [Analysis];Copper/bl [Blood];Copper/ur [Urine];Copper Radioisotopes;Drug Monitoring;Genetic Testing;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Liver/pa [Pathology];Liver Transplantation;Ophthalmoscopy;Penicillamine/ad [Administration & Dosage];Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Sulfates/ad [Administration & Dosage];Sulfates/pd [Pharmacology];Sulfates/tu [Therapeutic Use];Trientine/ad [Administration & Dosage];Trientine/pd [Pharmacology];Trientine/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];Zinc/pd [Pharmacology];Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Copper Radioisotopes);0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Yarze, J. C.;Martin, P.;Munoz, S. J.;Friedman, L. S.",1992,Jun,,0,0,
661,Thiomolybdates in the treatment of Wilson's disease,,*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Molybdenum/ae [Adverse Effects];*Molybdenum/tu [Therapeutic Use];81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Walshe, J. M.",1992,Feb,,0,0,
662,Diagnosing Wilson disease,,*Drug Monitoring/mt [Methods];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Sowa, J. M.",1992,Jul 01,,0,0,
663,The interactions of penicillamine with copper in vivo and the effect on hepatic metallothionein levels and copper/zinc distribution: the implications for Wilson's disease and arthritis therapy,"D-penicillamine does not remove copper from metallothionein, but it has been suggested that it may increase hepatic metallothionein levels. D-penicillamine was shown to increase rat hepatic metallothionein levels; however, the effect was dependent on an interaction with copper. The drug accelerated the excretion of exogenous copper but increased the amount retained on metallothionein. This interaction of penicillamine and copper also provoked changes in the distribution of zinc and in particular an increase in the heat-stable cytosol zinc fraction. In contrast, thiomolybdates were much more effective in eliminating exogenous copper and even removed copper that was already bound to metallothionein; thus, the copper level in the heat-stable cytosol fraction decreased. The observations support the view that patients with Wilson's disease may not be truly ""decoppered"" but that treatment with d-penicillamine is effective because the accumulated copper in the liver is bound in a nontoxic form by the increased metallothionein. The results explain why cessation of treatment is dangerous. The results may also partially explain the effectiveness of D-penicillamine copper chelates as antiinflammatory drugs.","Animals;*Arthritis/dt [Drug Therapy];Copper/ad [Administration & Dosage];*Copper/me [Metabolism];Copper/pk [Pharmacokinetics];Cytosol/de [Drug Effects];Cytosol/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Injections, Intramuscular;Liver/de [Drug Effects];*Liver/me [Metabolism];Male;*Metallothionein/me [Metabolism];Methionine/ad [Administration & Dosage];Methionine/pk [Pharmacokinetics];Molybdenum/pd [Pharmacology];Organometallic Compounds/ad [Administration & Dosage];Organometallic Compounds/pk [Pharmacokinetics];*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Rats;Rats, Inbred Strains;Reference Values;*Zinc/me [Metabolism];0 (Organometallic Compounds);13985-65-4 (copper methionate);789U1901C5 (Copper);81AH48963U (Molybdenum);9038-94-2 (Metallothionein);91U3TGV99T (tetrathiomolybdate);AE28F7PNPL (Methionine);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","McQuaid, A.;Lamand, M.;Mason, J.",1992,Jun,,0,0,
664,Pseudoxanthoma-elasticum-like skin changes induced by penicillamine,"The interference of penicillamine with collagen and elastin cross-linking can lead to wrinkling and anetoderma-like lesions in flexural areas as well as fragility and hemorrhagic blisters in pressure areas. These changes are seen primarily in patients with Wilson's disease or cystinuria who are on long-term therapy. This is a report of a patient with cystinuria on long-term, high-dose penicillamine who developed pseudoxanthoma-elasticum-like lesions. Coalescent yellow papules with a 'plucked-chicken skin' appearance were seen in the axillae and on the neck while redundant skin folds were noted in the anterior axillary line and lower buttocks. By light and electron microscopy, involved and uninvolved skin demonstrated 'lumpy-bumpy' dermal elastic fibers with no calcium deposition. These histologic changes are similar to those previously described in patients with penicillamine-induced skin lesions.","Aged;Collagen/de [Drug Effects];Elastin/de [Drug Effects];Humans;Male;Microscopy, Electron;*Penicillamine/ae [Adverse Effects];*Pseudoxanthoma Elasticum/ci [Chemically Induced];Pseudoxanthoma Elasticum/pa [Pathology];9007-34-5 (Collagen);9007-58-3 (Elastin);GNN1DV99GX (Penicillamine)","Bolognia, J. L.;Braverman, I.",1992,,,0,0,
665,Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson's disease,"To investigate the diagnostic value of 24-hr urinary copper excretion testing after penicillamine challenge in the diagnosis of Wilson's disease, 75 consecutive children referred for a variety of liver problems and in whom parameters of copper metabolism had been investigated were analyzed retrospectively. Seventeen had Wilson's disease, 22 had autoimmune chronic active hepatitis, 6 had primary sclerosing cholangitis, 12 had chronic liver disease of various etiologies, 4 had cryptogenic acute liver failure, 6 had acute hepatitic illnesses and 8 had a variety of disorders featuring normal liver histological appearance. Serum ceruloplasmin and total copper levels were significantly lower in Wilson's disease patients compared with all other groups, but three children with Wilson's disease had normal ceruloplasmin levels and seven had normal total copper levels. No significant difference was found for free serum copper levels and liver copper content between Wilson's disease patients and the other groups. Baseline 24-hr urinary copper excretion was significantly higher in Wilson's disease patients compared with that of the other patients, but six children with Wilson's disease had levels just above the upper limit of normal, overlapping with values obtained in three children with liver failure, two with acute hepatitis, two with autoimmune chronic active hepatitis and three with primary sclerosing cholangitis. The 24-hr urinary copper excretion after penicillamine challenge proved the most accurate single diagnostic test; levels more than 25 mumol/24 hr were present in 15 of 17 patients with Wilson's disease, but in only 1 child with liver failure of the 58 with other disorders.(ABSTRACT TRUNCATED AT 250 WORDS)","Adolescent;Ceruloplasmin/an [Analysis];Child;Child, Preschool;Copper/bl [Blood];Copper/me [Metabolism];*Copper/ur [Urine];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/ur [Urine];Humans;Liver/me [Metabolism];Male;*Penicillamine;Retrospective Studies;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Martins da Costa, C.;Baldwin, D.;Portmann, B.;Lolin, Y.;Mowat, A. P.;Mieli-Vergani, G.",1992,Apr,,0,0,
666,Treatment of Wilson's disease with zinc: X. Intestinal metallothionein induction,"Oral zinc therapy is effective in controlling copper balance in patients with Wilson's disease and blocks the intestinal absorption of copper, as demonstrated by uptake of copper 64 and copper balance measurements. In this study, 64Cu uptake measurements were concomitantly carried out with intestinal biopsies to investigate the relationship of reduced copper absorption to the levels of intestinal metallothionein in patients with Wilson's disease at different stages of zinc therapy. A pronounced increase in intestinal metallothionein levels and a sharp drop in 64Cu absorption were found 4 to 5 days after the initiation of zinc treatment. Conversely, metallothionein levels decreased and 64Cu uptake increased on the discontinuation of zinc therapy. The data indicate that 64Cu absorption varies as a function of intestinal metallothionein level. Intestinal metallothionein levels were found to correlate linearly with urinary zinc levels, which reflect body zinc status. These findings support our hypothesis that intestinal metallothionein induction mediates decreased copper absorption observed during zinc therapy. The suppressive effect of zinc on copper absorption appears to have a half-life of about 11 days.",Adult;Copper Radioisotopes/pk [Pharmacokinetics];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Intestinal Absorption/de [Drug Effects];*Intestines/me [Metabolism];Male;*Metallothionein/bi [Biosynthesis];Metallothionein/de [Drug Effects];Zinc/me [Metabolism];*Zinc/tu [Therapeutic Use];0 (Copper Radioisotopes);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc),"Yuzbasiyan-Gurkan, V.;Grider, A.;Nostrant, T.;Cousins, R. J.;Brewer, G. J.",1992,Sep,,0,0,
667,Oral zinc as initial therapy in Wilson's disease: two years of continuous treatment in a 10-year-old child,"Two years of continuous therapy promoted a significant overall amelioration in a 10-year-old boy affected by an hepatic form of Wilson's disease in which zinc sulphate was the sole therapy. In particular, liver function returned to normal and hepatic histology also improved. The parameters characterizing copper metabolism were kept under good control, and a decrease in copper concentration was found in both erythrocytes and liver. The copper balance study performed during the 25th month of treatment showed that oral zinc was still efficiently inhibiting the intestinal absorption of copper. No side effects have been reported so far.","Administration, Oral;Child;Copper/ai [Antagonists & Inhibitors];Copper/bl [Blood];Copper/me [Metabolism];Drug Administration Schedule;Erythrocytes/de [Drug Effects];Erythrocytes/me [Metabolism];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/de [Drug Effects];Liver/me [Metabolism];Liver Function Tests;Male;*Sulfates/ad [Administration & Dosage];Time Factors;*Zinc/ad [Administration & Dosage];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Milanino, R.;Deganello, A.;Marrella, M.;Michielutti, F.;Moretti, U.;Pasqualicchio, M.;Tamassia, G.;Tato, L.;Velo, G. P.",1992,Feb,,0,0,
668,Wilson's disease,"Fourteen cases of Wilson's disease in Thais were studied retrospectively. Most were in the second and third decades. The hepatic form occurs in all age groups and the most common presentation was cirrhosis and complications. Neurological complications were observed during the second decade and consisted of Parkinsonism, dystonic and pseudosclerotic forms. A Keyser-Fleisher ring was detected in 2/3 of the cases. D-penicillamine was the mainstay of our therapy. Death in this series was related to crisis such as acute hemolysis, hepatitis as well as septic complications of cirrhosis. Since Wilson's disease is a treatable and preventable disorder, early clinical diagnosis and screening of asymptomatic siblings is mandatory.",Adolescent;Adult;Child;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Humans;Male;Retrospective Studies,"Phanthumchinda, K.;Cheevinsiriwat, S.",1992,Mar,,0,0,
669,Wilson's disease: initial worsening of neurologic syndrome with penicillamine therapy,,Child;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Nervous System Diseases/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Syndrome;GNN1DV99GX (Penicillamine),"Kher, A.;Bharucha, B. A.;Kumta, N. B.",1992,Jul,,0,0,
670,Resolution of cerebral white matter lesions following long-term penicillamine therapy for Wilson's disease: report of a case,"Although lenticular gray matter lesions in Wilson's disease (WD) may resolve following long-term decoppering therapy, response of cerebral white matter lesions to such a treatment has not been reported. A patient with WD developed dystonia of the left hand and focal seizures involving the left upper limb with occasional generalization. CT disclosed a low density area in the right frontal white matter. Initiation of penicillamine therapy resulted in worsening of clinical manifestations, further extension of the right frontal lesion, and development of a new left parietal lesion. However, after five years of continued penicillamine therapy, clinical improvements were noted, including disappearance of the left parietal lesion and almost complete resolution of the right frontal lesion. The present case suggests that cerebral white matter lesions in WD may also respond to long-term chelating therapy.","Adult;*Brain/de [Drug Effects];Brain/pa [Pathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Male;*Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Huang, C. C.;Chu, N. S.",1992,Jun,,0,0,
671,[Zinc in the treatment of hepatolenticular degeneration: report of 3 cases],"Three patients with symptoms and signs of hepatolenticular degeneration (HLD) who developed serious renal side effects of D-penicillamine (DP) had their therapeutic schedule changed to zinc. Patient 1, a 55 year-old man had been well until 12 years old, when skeletal changes (osteomalacia) due to tubular renal disturbance began. His diagnosis of HLD had first been established at age of 32 when he presented with ""wing-beat"" tremor. He was then begun on DP and his neurological symptoms resolved within one year of initiating therapy but skeletal abnormalities remained unchanged as a sequel. During the next 22 years the patient was continued on DP therapy but with poor compliance. Then the reappearance of his neurological manifestations occurred several times. By the age of 53, after one year without therapy, his neurological status has worse. DP was reinstituted but some weeks later his renal laboratory parameters became severely affected. DP was discontinued and zinc sulfate (220 mg three times daily) was introduced. On this therapeutic regimen his renal laboratory parameters returned to previous level after one month. Within one year on this therapeutic regimen neurological manifestations were resolved. After 31 months on zinc treatment he remains neurologically asymptomatic and his renal function is satisfactory. Patient 2, a 41 year old woman had been her diagnosis of HLD at age of 20, when following the diagnosis of the disease in her old brother, she was found to have the laboratory features of HLD and bilateral Kayser-Fleischer rings. DP treatment was recommended at that time but she quit the follow-up. When she was 23, an esophageal variceal bleeding occurred.(ABSTRACT TRUNCATED AT 250 WORDS)",Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;Penicillamine/ae [Adverse Effects];*Sulfates/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Barbosa, E. R.;Burdmann Ede, A.;Cancado, E. R.;Haddad, M. S.;Scaff, M.;Canelas, H. M.",1992,Mar,,0,0,
672,"Wilson's disease treatment by triethylene tetramine dihydrochloride (trientine, 2HCl): long-term observations","Wilson's disease is an autosomal recessive disorder characterized by an accumulation of a toxic amount of copper in the body. Triethylene tetramine dihydrochloride (trientine, 2HCl) is a new chelating agent that may be effective in the removal of excess copper but long-term efficacy has not yet been investigated. Here we report the use of trientine over more than 8 years in 2 patients with Wilson's disease who could not tolerate D-penicillamine. We found no significant side effect, except a decreased serum iron concentration without clinical symptoms of anemia. In annual examinations at a steady state, the serum copper levels remained below 20 micrograms/100 ml. The 24-hour urinary copper excretion was less than that found using D-penicillamine, while the basal copper excretion, after 5 days abstinence from trientine, was maintained below 100 micrograms/day. Both hepatic and neurological manifestations except bulbar symptoms were recovered without any initial deterioration.",Adolescent;Adult;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Chelating Agents/ae [Adverse Effects];*Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Iron/bl [Blood];Male;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Trientine/ae [Adverse Effects];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);E1UOL152H7 (Iron);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Morita, J.;Yoshino, M.;Watari, H.;Yoshida, I.;Motohiro, T.;Yamashita, F.;Okano, Y.;Hashimoto, T.",1992,,,0,0,
673,Assessment of portal hypertension: understanding will improve treatment,"To many people it may be disappointing that many uncertainties remain with respect to the assessment of PHT. Only a few findings such as increased WHVPG and varices prove PHT. However, we have gained considerable knowledge. PHT is the consequence of a number of changes which involve the intrahepatic and extrahepatic circulation. Alcohol, viruses and drugs may disturb parenchymal architecture and cause cellular swelling, collagen and fibrin deposition and invasion with inflammatory cells. These processes finally may evolve into cirrhosis. Although in initial stages the parenchymal disturbance per se may account for PHT, increasingly impaired liver function results in metabolic changes which cause altered haemodynamics. Advanced PHT in parenchymal liver disease is the result of the complex interaction between local and systemic changes. The current techniques for the assessment of PHT are helpful for the qualitative aspects: increase in pressure can be assessed directly or indirectly; the portal venous system can be visualized even without arteriography. Gastroscopy remains a standard procedure for diagnosing PHT. Ultrasound-endoscopy is particularly helpful to confirm fundic varices and to assess changes after sclerotherapy. Increasingly, non-invasive methods to quantify PHT have become available such as the Duplex scanner. However, limitations and pitfalls need to be realized. The quantitative assessment remains (as yet?) a technique for research centres. It is obvious that the clinician in general practice can do without most of the more sophisticated techniques which have been discussed here. For the time being, PHT, and particularly variceal bleeding, is most often treated with endoscopic sclerotherapy. For that reason, only in a minority of the cases very detailed studies are required. However, the increasing knowledge opens new perspectives for the treatment and prevention of PHT on various levels. This may be a rather specific treatment of parenchymal liver disease (antivirals, d-penicillamine for Wilson's disease or venesections for haemochromatosis), drugs which may reduce local tissue damage via more general pathways (colchicine, steroids) and drugs which influence flow. Undoubtedly one of these years a more selective blocker of portal venous pressure will become available. Optimal assessment for that type of therapy makes it mandatory to master at least a few more advanced techniques. With respect to noncirrhotic PHT with causes which may vary from congenital or acquired clotting abnormalities to anatomical malformations (oesophageal web) and 'natural healthy herb tea', measures can be taken. It is clear that before treating any of the more rare causes, a proper diagnostic work-up is required.(ABSTRACT TRUNCATED AT 400 WORDS) [References: 92]","Diagnostic Imaging;Humans;Hypertension, Portal/di [Diagnosis];Hypertension, Portal/et [Etiology];*Hypertension, Portal;Liver/dg [Diagnostic Imaging];Liver Diseases/co [Complications];Portal System/pp [Physiopathology];Ultrasonography","van Leeuwen, D. J.",1991,,,0,0,
674,Prognosis of Wilsonian chronic active hepatitis,"Twenty of 320 patients with Wilson's disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis.","Adolescent;Adult;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Bilirubin/bl [Blood];Child;Copper/ae [Adverse Effects];Copper/an [Analysis];Female;Hepatitis, Chronic/bl [Blood];*Hepatitis, Chronic/dt [Drug Therapy];Hepatitis, Chronic/et [Etiology];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/ch [Chemistry];Liver/pa [Pathology];Liver Cirrhosis/et [Etiology];Liver Cirrhosis/pa [Pathology];Male;*Penicillamine/tu [Therapeutic Use];Prognosis;Serum Albumin/an [Analysis];*Trientine/tu [Therapeutic Use];0 (Serum Albumin);789U1901C5 (Copper);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin);SJ76Y07H5F (Trientine)","Schilsky, M. L.;Scheinberg, I. H.;Sternlieb, I.",1991,Mar,,0,1,
675,Initial therapy of patients with Wilson's disease with tetrathiomolybdate,"Patients with Wilson's disease who present with acute neurological symptoms often become clinically worse when initially treated with penicillamine. Other available anticopper drug therapies do not appear to offer a solution to this treatment problem. We are developing and evaluating a new drug, ammonium tetrathiomolybdate for this purpose. Theoretically, tetrathiomolybdate has optimal properties, including an immediate blockade of copper absorption and the property of forming complexes with copper in the blood, rendering the copper nontoxic. In this article, we present results from six patients treated with tetrathiomolybdate for up to 8 weeks as initial therapy. None of the five patients who had presented with acute neurological symptoms worsened. Also presented are methods of assay, preliminary stability studies, and methods of evaluating therapeutic end points with respect to copper metabolism.",Adolescent;Adult;Ceruloplasmin/me [Metabolism];Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Molybdenum/tu [Therapeutic Use];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);EC 1-16-3-1 (Ceruloplasmin),"Brewer, G. J.;Dick, R. D.;Yuzbasiyan-Gurkin, V.;Tankanow, R.;Young, A. B.;Kluin, K. J.",1991,Jan,,0,0,
676,Excellent prognosis in Wilsonian chronic active hepatitis: new data or an article of faith?,,"Hepatitis, Chronic/bl [Blood];Hepatitis, Chronic/dt [Drug Therapy];*Hepatitis, Chronic/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Humans;Liver Cirrhosis/et [Etiology];Penicillamine/tu [Therapeutic Use];Prognosis;Trientine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Johnson, P. J.;Williams, R.",1991,Dec,,0,0,
677,Penicillamine treatment of Wilson's disease and optic neuropathy,,"Adult;Color Perception/de [Drug Effects];Dose-Response Relationship, Drug;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Optic Nerve Diseases/ci [Chemically Induced];Optic Nerve Diseases/di [Diagnosis];Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];Visual Acuity/de [Drug Effects];GNN1DV99GX (Penicillamine)","Lee, A. H.;Lawton, N. F.",1991,Aug,,0,0,
678,Treatment of Wilson's disease with zinc. IX: Response of serum lipids,"Zinc therapy in Wilson's disease is a lifelong treatment to prevent reaccumulation of copper. Previous reports have shown that in normal male subjects, zinc ingestion has reduced high-density lipoprotein cholesterol level. This finding raises the possibility that lifelong zinc therapy could be atherogenic. In the present work, the effects of zinc therapy on serum lipids over a period of years is evaluated in patients with Wilson's disease. Zinc therapy reduces total cholesterol level by about 10% in both sexes and reduces high-density lipoprotein cholesterol level by about 20% in male patients. The mechanisms of these interesting effects of zinc on cholesterol metabolism are unknown. The coronary heart disease risk factor is not changed significantly by zinc therapy in either sex, and further, it remains below average in these patients after zinc therapy. We conclude that zinc therapy in Wilson's disease is not atherogenic.","Cholesterol, HDL/bl [Blood];Coronary Disease/ep [Epidemiology];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lipids/bl [Blood];Male;Risk Factors;Sex Characteristics;*Zinc/tu [Therapeutic Use];0 (Cholesterol, HDL);0 (Lipids);J41CSQ7QDS (Zinc)","Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Johnson, V.",1991,Nov,,0,0,
679,"Wilson disease: clinical presentation, treatment, and survival","OBJECTIVE: To evaluate the diagnostic features, clinical course, and overall long-term survival of patients with Wilson disease. DESIGN: Retrospective cohort study with a mean follow-up period of 14.2 years. SETTING: A university medical center and a community hospital. PATIENTS: Fifty-one consecutive patients with Wilson disease were evaluated between 1957 and 1989. INTERVENTIONS: Patients were treated with D-penicillamine (600 to 1800 mg/d). Two patients with end-stage liver disease had liver transplantation. MAIN RESULTS: Initial symptoms occurred at a mean age of 15.5 years. At diagnosis, the most common neurologic signs were dysarthria, tremor, writing difficulties, and ataxia followed by hypersalivation and headache. Somatic symptoms included abdominal pain, hepatomegaly, splenomegaly, cirrhosis of the liver, and thrombocytopenia. The mean serum concentrations of ceruloplasmin and copper were 44 mg/L and 4.7 mumol/L, respectively. The mean basal urinary copper excretion was 5.5 mumol/d, and the mean hepatic copper concentration was 19.6 mumol/g dry weight. Free serum copper concentration (mean, 2.7 mumol/L) was a reliable indicator of disease and was useful in assessing the effectiveness of therapy (values less than 1.6 mumol/L). Treatment with D-penicillamine improved most of the hematologic and neurologic abnormalities but had little effect on hepatomegaly and splenomegaly and did not reverse cirrhosis. Two patients died of fulminant hepatic failure during the observation period, whereas two others with end-stage liver disease had successful liver transplantation and remain asymptomatic. Long-term survival of patients with Wilson disease was similar to that of age- and sex-matched controls. CONCLUSION: Our results suggest that long-term treatment of patients with Wilson disease with D-penicillamine can relieve symptoms and improve prognosis.",Adolescent;Female;Follow-Up Studies;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration/th [Therapy];Humans;*Liver Transplantation;Male;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Retrospective Studies;Survival Rate;GNN1DV99GX (Penicillamine),"Stremmel, W.;Meyerrose, K. W.;Niederau, C.;Hefter, H.;Kreuzpaintner, G.;Strohmeyer, G.",1991,Nov 01,,0,0,
680,Triethylene-tetramine (trien) therapy for Wilson's disease,"Triethylene tetramine (trien), in increasing dose from 1.0-2.0 g/day to 2.5-3.0 g/day, was used for 4 Japanese patients with Wilson's disease who were intolerant of D-penicillamine (D-PC). Before the treatment, urinary copper excretion (UCE) was 70-96 micrograms/day. UCE increased to 1,512-2,352 micrograms/day on the day of initial administration, and remained at levels between 350-1,100 micrograms/day, thereafter. During 2 months of trien therapy, neurological deficits regressed in three patients, and only slightly in one patient. No adverse effects were observed. These results and the retrospective survey on 17 patients treated with D-PC confirmed that trien is less potent but a safer copper chelating agent than D-PC. The transient aggravation of neurological deficits seen in two patients during the early stage of the treatment suggested that trien, as D-PC, should be started in small doses and gradually increased.",Adolescent;Adult;*Chelating Agents/tu [Therapeutic Use];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/ae [Adverse Effects];*Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Saito, H.;Watanabe, K.;Sahara, M.;Mochizuki, R.;Edo, K.;Ohyama, Y.",1991,May,,0,1,
681,Mid-brain pathology of Wilson's disease: MRI analysis of three cases,"MRI scans were obtained from three patients with Wilson's disease, all of whom showed rigidity and dysarthria; two also showed tremor and dystonia. Two had been treated with D-penicillamine for seven and 14 years, respectively and their neurological abnormalities had improved, but the third patient had not been treated. T2-weighted MRI of the mid-brain in all three revealed the characteristic ""face of the giant panda"" sign, consisting of high signal intensity in the tegmentum except for red nucleus, preservation of signal intensity of the lateral portion of the pars reticulata of the substantia nigra and hypo-intensity of the superior colliculus. The clinical significance of these MRI abnormalities is discussed.","Adolescent;Adult;Atrophy;Basal Ganglia/pa [Pathology];Basal Ganglia Diseases/di [Diagnosis];Brain/pa [Pathology];*Brain Damage, Chronic/di [Diagnosis];*Brain Stem/pa [Pathology];Female;*Hepatolenticular Degeneration/di [Diagnosis];Humans;*Magnetic Resonance Imaging;Male;Tegmentum Mesencephali/pa [Pathology]","Hitoshi, S.;Iwata, M.;Yoshikawa, K.",1991,Jul,,0,0,
682,Mode of action of triethylenetetramine dihydrochloride on copper metabolism in Wilson's disease,"The drug of choice for the initial treatment of ""decoppering"" in Wilson's disease, an inherited disorder of copper metabolism, is the chelating agent D-penicillamine. In the case of harmful side-effects an alternative drug is triethylenetetramine dihydrocholoride (trien or trientine). Using the 24-h-urine excretion of copper and the oral copper loading test with copper-64, a double function for trien was found: trien increases the urine copper excretion and decreases the intestinal copper absorption respectively.","Adult;*Copper/ur [Urine];Drug Administration Schedule;Drug Therapy, Combination;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Sulfates/tu [Therapeutic Use];*Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Siegemund, R.;Lossner, J.;Gunther, K.;Kuhn, H. J.;Bachmann, H.",1991,Jun,,0,0,
683,Pregnancy and Wilson's disease,,Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications;Sulfates/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Chin, R. K.",1991,Aug,,0,0,
684,Antidotal effects of dimercaptosuccinic acid,"Dimercaptosuccinic acid (DMS), HOOC-CH(SH)-CH(SH)-COOH, was first developed in China as an effective antidote for poisoning from many heavy metals, such as Pb, Hg, As, Cd, Sb, Tl, Au, Zn, Ni, Pt, Ag, Co and Sn. DMS increases the excretion of Ce, Pm, Sr and Po from the body. Hundreds of patients suffering from hepatolenticular degeneration (Wilson's disease) have been treated successfully with DMS. Recently, DMS was found to be effective also in treating certain non-metallic intoxications, like some of the new non-phosphate pesticides and mushroom poisonings. [References: 151]",Animals;*Antidotes/pd [Pharmacology];Humans;Metals/po [Poisoning];Poisoning/dt [Drug Therapy];*Succimer/pd [Pharmacology];Succimer/to [Toxicity];0 (Antidotes);0 (Metals);DX1U2629QE (Succimer),"Ding, G. S.;Liang, Y. Y.",1991,Feb,,0,0,
685,The psychiatric presentations of Wilson's disease,"We reviewed the records of 42 patients with Wilson's disease participating in a zinc acetate treatment protocol and interviewed 17 of them. Five of the patients studied were asymptomatic. A significant number of symptomatic patients (64.8%) reported psychiatric symptoms at the time of initial presentation. These symptoms were severe enough to warrant psychiatric intervention in almost half of all symptomatic patients before the diagnosis of Wilson's disease was made. Personality changes, particularly irritability and aggression, were most commonly described (45.9%), followed by depression (27%). Cognitive changes, anxiety, psychosis, and catatonia, while less frequent, also occurred. These data underscore the need to include Wilson's disease in the differential diagnosis of psychiatric disorders.",Acetates/tu [Therapeutic Use];Acetic Acid;Adult;Depressive Disorder/di [Diagnosis];Depressive Disorder/dt [Drug Therapy];Depressive Disorder/px [Psychology];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Humans;Magnetic Resonance Imaging;Male;*Neurocognitive Disorders/di [Diagnosis];Neurocognitive Disorders/dt [Drug Therapy];Neurocognitive Disorders/px [Psychology];Neurologic Examination;*Neuropsychological Tests;Personality Disorders/di [Diagnosis];Personality Disorders/dt [Drug Therapy];Personality Disorders/px [Psychology];0 (Acetates);Q40Q9N063P (Acetic Acid),"Akil, M.;Schwartz, J. A.;Dutchak, D.;Yuzbasiyan-Gurkan, V.;Brewer, G. J.",1991,Fall,https://dx.doi.org/10.1176/jnp.3.4.377,0,0,
686,D-penicillamine,,Child;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;India;Liver Cirrhosis/bl [Blood];*Liver Cirrhosis/dt [Drug Therapy];Penicillamine/ae [Adverse Effects];Penicillamine/pk [Pharmacokinetics];*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Singh, S.;Kohli, V.",1991,Jul,,0,0,
687,Pathophysiology and treatment of Wilson's disease,"The pathophysiology, symptomatology, and treatment of Wilson's disease are reviewed, and new approaches to drug management are discussed. Wilson's disease is a rare, autosomal recessive disorder that occurs between the ages of 6 and 60 years. Disturbances in copper metabolism may result in the accumulation of excess copper in the liver, the basal ganglia of the brain (lenticular degeneration), the kidneys, the cornea (Kayser-Fleischer rings), and other tissues. The diagnosis of Wilson's disease is frequently overlooked; nonspecific symptoms and multisystem involvement may mimic other disease states, such as neurologic and psychiatric disorders, and hemolytic anemia. Screening tests for Wilson's disease include 24-hour urinary copper levels, serum ceruloplasmin and copper assays, radioactive uptake of 64Cu, and liver biopsy. Current methods of therapy include the use of a chelating agent--penicillamine or trientine--for initial rapid decoppering. Penicillamine therapy has been associated with many adverse reactions, including worsening of the neurologic symptoms of the patient. Zinc is a useful agent for maintenance therapy. Investigational studies exploring the use of ammonium tetrathiomolybdate for initial rapid decoppering have shown promising results. Unless it is recognized and treated, Wilson's disease can cause severe symptoms and, ultimately, death. Initial rapid decoppering with chelating agents, such as penicillamine and trientine, followed by lifelong maintenance therapy with zinc is the current method of treatment. [References: 85]",Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration/th [Therapy];Humans,"Tankanow, R. M.",1991,Nov,,0,0,
688,Case update--progressive skin laxity secondary to penicillamine treatment,,Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Middle Aged;*Penicillamine/ae [Adverse Effects];*Skin Aging/de [Drug Effects];GNN1DV99GX (Penicillamine),"Buckley, C.;Sankey, E. A.;Harris, D.;Wright, S.",1991,Jul,,0,0,
689,Wilson's disease in Scotland,"The prevalence and clinical features of Wilson's disease in Scotland were investigated. Thirty three cases were identified but adequate information was available on only 28. In 1989, the prevalence rate was 4 per million. Ten patients with a mean (SEM) age of 18 (1.9) years presented with neurological symptoms, 12 patients aged 14 (1.7) years presented with hepatic symptoms, and six patients aged 12 (0.9) years were asymptomatic siblings of patients with Wilson's disease. Nine (56%) of the 16 patients who underwent liver biopsy on presentation were found to have cirrhosis. Penicillamine treatment was stopped in nine patients because of: abnormal peripheral blood count (6), rash (2), and patient's own choice (1). Nineteen patients were alive in 1989 -12 were well, one had chronic liver failure, four chronic neurological disabilities, and two had both chronic liver failure and neurological disabilities. Twelve patients died from: complications of chronic liver failure (2), acute liver failure (4), pneumonia associated with immobility (4), and other causes (2). Several patients who died had received incomplete medical supervision.",Adolescent;Child;Female;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ep [Epidemiology];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/mo [Mortality];Humans;Male;Penicillamine/tu [Therapeutic Use];Prevalence;Scotland/ep [Epidemiology];GNN1DV99GX (Penicillamine),"Park, R. H.;McCabe, P.;Fell, G. S.;Russell, R. I.",1991,Dec,,0,1,
690,Copper metallothionein in patients with hepatic copper overload,"We studied the Cu-MT present in the hepatic cytosol obtained from 7 patients suffering from conditions associated with hepatic Cu overload (Wilson's disease, biliary atresia, familial cholestatic cirrhosis). Since chromatographic methods appropriate for the isolation of Zn- and Cd-MT were unsuitable for Cu-MT, we developed an indirect procedure for the estimation and resolution of the latter. This procedure involved the preparation of apo-MT and its reconstitution to holo-MT with Zn or Cd. Three predominant isoforms of MT were present in all specimens. Our results indicate that at most 36 +/- 5% of the Cu present in the 10 kDa fraction of cytosol is bound to MT in the liver of patients with hepatic copper overload.","Adolescent;Adult;Biliary Atresia/me [Metabolism];Child;Child, Preschool;*Copper/me [Metabolism];Cytosol/me [Metabolism];Female;Hepatolenticular Degeneration/me [Metabolism];Humans;*Liver/me [Metabolism];Liver Cirrhosis, Biliary/me [Metabolism];Male;*Metallothionein/me [Metabolism];0 (copper thionein);789U1901C5 (Copper);9038-94-2 (Metallothionein)","Hunziker, P. E.;Sternlieb, I.",1991,Oct,,0,0,
691,Successful pregnancy after D-penicillamine therapy in a patient with Wilson's disease,"Infertility and amenorrhea are reported in most cases of Wilson's disease. In this report, we describe a case of Wilson's disease with pancytopenia and liver cirrhosis for over 4 years, without any specific treatment. After 2 years of D-penicillamine therapy, the patient became pregnant and delivered a liver mature female baby with a body weight of 2,800 g. Both before the pregnancy and after delivery, brainstem auditory evoked potential studies showed similar bilaterally abnormal prolongation in the III-V and I-V intervals. In visual evoked potentials, the P 100 latency was delayed bilaterally. Although serial evoked potential studies failed to show any improvement, a successful pregnancy was proven to be possible in a patient with Wilson's disease who had received regular D-penicillamine treatment.","Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;*Penicillamine/tu [Therapeutic Use];*Pregnancy;GNN1DV99GX (Penicillamine)","Soong, Y. K.;Huang, H. Y.;Huang, C. C.;Chu, N. S.",1991,Jul,,0,0,
692,Abnormal conduction in corticospinal pathways in Wilson's disease: investigation of nine cases with magnetic brain stimulation,"Electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation were studied in nine patients with Wilson's disease (WD). Six of the nine patients had prolonged central motor latencies (CMLs), reduced amplitude, or absent responses in at least one of the examined muscles. In one patient, abnormal EMG responses normalized following treatment with penicillamine. Pathophysiologically abnormal EMG responses might result from a potentially reversible impairment of corticomotoneuronal pathways and/or a reduced excitability of motoneurons due to basal ganglia dysfunction. The possible pathophysiological mechanisms are discussed.",Adult;*Electromagnetic Fields;*Electromyography;Follow-Up Studies;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Motor Cortex/de [Drug Effects];*Motor Cortex/pp [Physiopathology];Muscle Contraction/de [Drug Effects];Muscle Contraction/ph [Physiology];*Muscles/ir [Innervation];Neurologic Examination;Penicillamine/tu [Therapeutic Use];Pyramidal Tracts/de [Drug Effects];*Pyramidal Tracts/pp [Physiopathology];Synaptic Transmission/de [Drug Effects];*Synaptic Transmission/ph [Physiology];GNN1DV99GX (Penicillamine),"Meyer, B. U.;Britton, T. C.;Bischoff, C.;Machetanz, J.;Benecke, R.;Conrad, B.",1991,,https://dx.doi.org/10.1002/mds.870060409,0,0,
693,The pancreas and zinc homeostasis,,Absorption;Diet;Female;Hepatolenticular Degeneration/me [Metabolism];*Homeostasis;Humans;Intestines/me [Metabolism];Male;Metallothionein/me [Metabolism];*Pancreas/me [Metabolism];Phytic Acid/ad [Administration & Dosage];Phytic Acid/pd [Pharmacology];Zinc/df [Deficiency];*Zinc/me [Metabolism];Zinc/pk [Pharmacokinetics];7IGF0S7R8I (Phytic Acid);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc),"McClain, C. J.",1990,Sep,,0,0,
694,Oral zinc sulphate treatment in Wilson's disease,,Adult;Child;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Sulfates/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];Zinc/ur [Urine];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Pasqualicchio, M.;Marrella, M.;Moretti, U.;Velo, G. P.;Deganello, A.;Tomelleri, G.;Milanino, R.",1990,,,0,0,
695,Zinc therapy in Wilson's disease: observations in five patients,"We report our experience with zinc (Zn) therapy in five patients with Wilson's disease (WD). In addition to neurologic examination, evaluation of Kayser-Fleischer rings and liver function tests, copper (Cu) and Zn concentrations in liver tissue, plasma, and urine were periodically evaluated by spectrophotometry. Many of the patients had had side effects due to penicillamine (PCA). Oral Zn sulphate (220 mg tid) reduced the WD symptoms and resulted in normal urinary Cu excretion in all five patients. One patient who had a transient gastric complaint during Zn administration, and in whom a decrease in liver Cu content was not observed, did not show any improvement in liver histology. He resumed PCA therapy after 29 months of Zn therapy. We conclude that long-term Zn treatment in Wilson's disease can be a safe and effective alternative to Cu chelating agents. However, patients should be periodically monitored for their Cu/Zn status to assess patient compliance with therapy.",Adolescent;Adult;*Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Liver Function Tests;Male;Penicillamine/tu [Therapeutic Use];Time Factors;*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Rossaro, L.;Sturniolo, G. C.;Giacon, G.;Montino, M. C.;Lecis, P. E.;Schade, R. R.;Corazza, G. R.;Trevisan, C.;Naccarato, R.",1990,Jun,,0,0,
696,[High field magnetic resonance imaging in Wilson's disease],"Magnetic resonance imaging studies on 3 cases with Wilson's disease were performed, using high field magnetic resonance system of 1.5 tesla. All patients had neurological findings of tremor, rigidity, dystonia or dysarthria at onset. Two patients had been treated with D-penicillamine for 14 years and 7 years respectively, and one patient was not treated then. T2-weighted images revealed abnormalities of signal intensity in lenticular nucleus, thalamus, pulvinar, superior colliculus, lateral portion of substantia nigra, midbrain and pontine tegmentum, and cerebral and cerebellar white-matter. Especially noted were following three hitherto undescribed abnormalities; high signal intensity of globus pallidus which normally shows very low signal intensity, restoration of signal intensity of lateral portion of substantia nigra, and marked low signal intensity of pulvinar and superior colliculus.",Adolescent;Adult;Female;Globus Pallidus/pa [Pathology];*Hepatolenticular Degeneration/di [Diagnosis];Humans;Magnetic Resonance Imaging/mt [Methods];Male;Substantia Nigra/pa [Pathology];Superior Colliculi/pa [Pathology],"Hitoshi, S.;Nangaku, M.;Shimada, H.;Yamada, H.;Yoshikawa, H.;Iwata, M.",1990,Feb,,0,0,
697,Wilson's disease. Development of neurological disease after beginning penicillamine therapy,"Patients with neurological symptoms and signs of Wilson's disease have been frequently noted to have a worsening of their condition after beginning chelation therapy with D-penicillamine. Presymptomatic patients, however, are not expected to develop neurological manifestations once appropriate therapy is begun. We describe a patient who was seen with hepatic disease and no neurological symptoms who became neurologically incapacitated soon after beginning penicillamine therapy. This case identifies an unexpected complication of penicillamine therapy that should be watched for in the presymptomatic patient who is beginning therapy.","Adult;Behavior;Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Imaging;Male;*Nervous System Diseases/ci [Chemically Induced];Nervous System Diseases/di [Diagnosis];Nervous System Diseases/px [Psychology];*Penicillamine/ae [Adverse Effects];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Glass, J. D.;Reich, S. G.;DeLong, M. R.",1990,May,,0,0,
698,Treatment of Wilson's disease with triethylene tetramine hydrochloride (Trientine),"Penicillamine is the drug of choice for the treatment of Wilson's disease, whatever the stage of the illness. Toxic manifestations may preclude the use of this life-saving drug in some patients and discontinuation of penicillamine therapy usually leads to death. We report our experience with Trientine in seven patients, aged 13 to 33 years, with Wilson's disease who developed toxic manifestations with penicillamine that required discontinuation of therapy. These include two with nephrosis, one with neutropenia, two with thrombocytopenia, and one each with a SLE-like and a Henoch-Schonlein-like syndrome. The patients were treated for periods from 6 weeks to 16 years with a dose of 0.5 to 2 g/day. Trientine proved to be an effective alternative copper chelating agent in the treatment of Wilson's disease in patients with penicillamine-induced neutropenia, thrombocytopenia, SLE, and nephrosis. No serious untoward side effects were noted.","Administration, Oral;Adolescent;Adult;Drug Evaluation;*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/po [Poisoning];Penicillamine/tu [Therapeutic Use];Trientine/ad [Administration & Dosage];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Dubois, R. S.;Rodgerson, D. O.;Hambidge, K. M.",1990,Jan,,0,0,
699,Macromastia in a woman treated with penicillamine and oral contraceptives. A case report,"A patient with Wilson's disease treated with penicillamine developed severe hirsutism. After treatment with oral contraceptives, her breasts enlarged rapidly, and she experienced cyclic mastodynia. Around the time of her breast enlargement she also developed gingival hyperplasia.","Adult;*Breast/de [Drug Effects];Breast/pa [Pathology];Contraceptives, Oral, Combined/ae [Adverse Effects];Contraceptives, Oral, Combined/tu [Therapeutic Use];*Contraceptives, Oral, Synthetic/ae [Adverse Effects];Contraceptives, Oral, Synthetic/tu [Therapeutic Use];Ethinyl Estradiol/ae [Adverse Effects];Ethinyl Estradiol/tu [Therapeutic Use];Female;Gingival Hyperplasia/ci [Chemically Induced];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hirsutism/ci [Chemically Induced];Hirsutism/dt [Drug Therapy];Humans;Norethindrone/ae [Adverse Effects];Norethindrone/tu [Therapeutic Use];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];0 (Contraceptives, Oral, Combined);0 (Contraceptives, Oral, Synthetic);37270-71-6 (norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination);423D2T571U (Ethinyl Estradiol);GNN1DV99GX (Penicillamine);T18F433X4S (Norethindrone)","Rose, B. I.;LeMaire, W. J.;Jeffers, L. J.",1990,Jan,,0,0,
700,Low-dose zinc therapy for maintenance treatment of Wilson's disease,,"Administration, Oral;Adult;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Copper/bl [Blood];Copper/me [Metabolism];Copper/ur [Urine];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Penicillamine/ae [Adverse Effects];Sulfates/ad [Administration & Dosage];*Sulfates/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Mayet, I. Y.",1990,Dec,,0,0,
701,Quantitation of Cu-containing metallothionein by a Cd-saturation method,"A rapid and sensitive method for determining Cu-containing metallothionein (MT) is described. The main features of this Cd-saturation assay are: high-molecular-weight Cd-binding compounds are denatured with acetonitrile (50% final concentration), Cu bound to MT is removed with ammonium tetrathiomolybdate, excessive tetrathiomolybdate and its Cu complexes are removed with DEAE-Sephacel, apothionein is saturated with Cd, and excessive Cd is bound to Chelex 100. The thiomolybdate assay is capable of reliably detecting 14 ng MT and thus is particularly suitable for measuring MT in small tissue samples (e.g., biopsies), in extrahepatic tissues, and in cultured cells. Moreover, the combination of the thiomolybdate assay with the recently developed Cd-Chelex assay also makes it possible to determine the portion of MT which binds Cu (Cu load of MT), provided that the amount of non-Cu-thionein exceeds 100 ng, the detection limit of the Cd-Chelex assay.","Animals;*Cadmium/me [Metabolism];Cadmium Radioisotopes;Cells, Cultured;Chemistry Techniques, Analytical/mt [Methods];Child;Child, Preschool;Chromatography, Gel;Copper/me [Metabolism];Cysteine/me [Metabolism];Ethanolamines;Fibroblasts/cy [Cytology];Fibroblasts/me [Metabolism];Glutathione/me [Metabolism];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Metallothionein/me [Metabolism];Molybdenum;Rats;Rats, Inbred Strains;0 (Cadmium Radioisotopes);0 (Ethanolamines);0 (copper thionein);00BH33GNGH (Cadmium);789U1901C5 (Copper);81AH48963U (Molybdenum);9038-94-2 (Metallothionein);91U3TGV99T (tetrathiomolybdate);GAN16C9B8O (Glutathione);K848JZ4886 (Cysteine);S6DL4M053U (2-diethylaminoethanol)","Klein, D.;Bartsch, R.;Summer, K. H.",1990,Aug 15,,0,0,
702,Cerebral abnormalities in Wilson's disease as evaluated by ultra-low-field magnetic resonance imaging and computerized image processing,"The cerebral involvement of a 13-yr-old boy with Wilson's disease was serially evaluated during the first 18 mo of D-penicillamine treatment. An ultra-low-field magnetic resonance imaging (ULF MRI) system, operating at 0.02 T, with computerized image processing was used. The half-yr period prior to the clinical diagnosis was set, the patient had showed poor school performance, emotional lability, deteriorating handwriting, progressively slow, gross, and fine motor functions, and a fixed rigid smile. No overt signs of liver disease were found. With D-penicillamine treatment (1-1.5 g/d) a continuous improvement was seen. The pretreatment MRI investigation showed pronounced pathological transformation in the basal ganglia. However, changes were seen also in most other parts of the brain indicating diffuse involvement. During treatment the computerized MR images became gradually more normal. The current magnetic resonance imaging system with computerized image processing is a sensitive and simple method for evaluation of subtle parenchymal changes of the brain.","Adolescent;*Brain/pa [Pathology];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;*Image Processing, Computer-Assisted;Magnetic Resonance Imaging/mt [Methods];*Magnetic Resonance Imaging;Male","Linne, T.;Agartz, I.;Saaf, J.;Wahlund, L. O.",1990,,,0,0,
703,Involvement of corticospinal tract in Wilson's disease. A study of three cases with transcranial stimulation,"Muscle responses evoked by transcranial stimulation were studied in three patients with Wilson's disease. Abnormalities indicating involvement of corticospinal tract were demonstrated in one patient. In keeping with recent evoked potential studies, this finding suggests that lesions in Wilson's disease may affect structures other than the extrapyramidal system.",Adolescent;Adult;Electric Stimulation;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Muscle Contraction/ph [Physiology];*Muscles/ir [Innervation];Penicillamine/ad [Administration & Dosage];*Pyramidal Tracts/pp [Physiopathology];Reaction Time/ph [Physiology];Trientine/ad [Administration & Dosage];GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Berardelli, A.;Inghilleri, M.;Priori, A.;Thompson, P. D.;Fabri, S.;Fieschi, C.;Manfredi, M.",1990,,https://dx.doi.org/10.1002/mds.870050416,0,0,
704,Use of zinc-copper metabolic interactions in the treatment of Wilson's disease,"Zinc acetate is becoming a well-established therapy for the treatment of Wilson's disease. It is excellent for maintenance therapy and for the treatment of the presymptomatic patient. Current evidence suggests that it will also be excellent for the treatment of the pregnant patient. Zinc acts by inducing intestinal cell metallothionein, which binds copper with high affinity, blocking its absorption, and causing its excretion in the stool. We have shown that zinc, even in doses as low as 25 mg daily, negatively affects copper balance. Zinc in doses of 50 mg three times daily, with all doses separated from food, controls the abnormal positive copper balance, blocks uptake of orally administered 64Cu, controls urine and plasma copper, prevents the reaccumulation of hepatic copper, and prevents the development or progression of symptoms of copper toxicosis in Wilson's disease patients. Zinc acetate will probably be licensed in the near future for the treatment of Wilson's disease. We recommend that physicians use urine and plasma copper, and urine zinc, as primary monitoring tools. In contrast to the comfortable situation with maintenance therapy, the initial treatment of acutely ill Wilson's disease patients is not well worked out. Patients with neurological disease often get worse initially on penicillamine, and zinc acts more slowly than is ideal. We have initiated studies of tetrathiomolybdate for this purpose. Studies of biliary secretions of normal subjects suggest that they excrete regulatory (excess) copper packaged in a protease-resistant ceruloplasmin fragment. This fragment is missing in Wilson's disease bile. The gene for Wilson's disease is on chromosome 13, close to the retinoblastoma locus.(ABSTRACT TRUNCATED AT 250 WORDS) [References: 23]",Acetates/pk [Pharmacokinetics];*Acetates/tu [Therapeutic Use];Acetic Acid;*Copper/me [Metabolism];Drug Interactions;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Zinc/me [Metabolism];0 (Acetates);789U1901C5 (Copper);J41CSQ7QDS (Zinc);Q40Q9N063P (Acetic Acid),"Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Lee, D. Y.",1990,Oct,,0,0,
705,"A review of the biochemical roles, toxicity and interactions of zinc, copper and iron: II. Copper","Copper is an essential nutrient for living matter. Through its cuproenzymes, copper displays a variety of metabolic functions. Atomic absorption spectrophotometry, radioisotope studies and establishment of cell and molecular biology have provided the necessary tools to study copper absorption, metabolism, physiology and biochemistry. The vital role of metallothionein in copper homeostasis is examined. Ceruloplasmin represents the molecular link between copper and iron metabolism. The genetic predisposition of copper toxicity has been attributed to the cause of Wilson's disease in humans. The interrelationships between copper and other dietary factors is addressed. [References: 0]",Animals;Chemical Phenomena;Chemistry;*Copper/me [Metabolism];Copper/to [Toxicity];Drug Interactions;Humans;Nutritional Requirements;789U1901C5 (Copper),"Abdel-Mageed, A. B.;Oehme, F. W.",1990,Jun,,0,0,
706,Liver copper concentration in Wilson's disease: effect of treatment with 'anti-copper' agents,"Serial copper determinations have been made on the livers of 10 patients with Wilson's disease. Two were studied before and eight after the start of treatment in order to assess the effect, if any, on the concentration of the metal. In two patients who were receiving no therapy and in one in whom it had been discontinued, the level of copper rose. In the latter patient, resumption of treatment then resulted in a fall in the level of copper in the liver. A similar fall was seen in seven patients on continuous therapy. In one patient, a very poor complier, there was a tendency for the liver copper concentration to rise over a 5-year period. All three therapies investigated--penicillamine, trientine and tetrathiomolybdate--when taken regularly, appear to be effective in reducing liver copper levels. Sixty-nine single determinations of liver copper have been plotted against time on treatment. This shows that the copper concentration falls rapidly in the first year. Thereafter, there is no linear relationship between the duration of treatment and liver copper. Poor compliers have a higher liver copper concentration than do good compliers. Determinations made from different portions of the liver showed that in only one of 19 examples was there an overlap between the near normal and the abnormal range. The principal mechanism of action of 'anti-copper' agents in Wilson's disease appears to be the mobilization of copper from the tissues, but a secondary detoxifying action may come into play later.",*Chelating Agents/tu [Therapeutic Use];*Chelation Therapy;*Copper/an [Analysis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;*Liver/ch [Chemistry];Time Factors;0 (Chelating Agents);789U1901C5 (Copper),"Gibbs, K.;Walshe, J. M.",1990,Jul-Aug,,0,0,
707,[Prenatal diagnosis: a chance? risk? dilemma?],,"Abortion, Induced/px [Psychology];Adult;Decision Making;Ethics, Medical;Female;*Fetal Diseases/di [Diagnosis];Fetal Diseases/px [Psychology];Fetal Diseases/th [Therapy];Humans;Infant, Newborn;*Metabolism, Inborn Errors/di [Diagnosis];Metabolism, Inborn Errors/px [Psychology];Metabolism, Inborn Errors/th [Therapy];Pregnancy;*Prenatal Diagnosis","Czartoryska, B.",1990,,,0,0,
708,Evoked potentials in assessment and follow-up of patients with Wilson's disease,"Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.","Administration, Oral;Adult;Brain Chemistry;Child;Copper/an [Analysis];Evaluation Studies as Topic;*Evoked Potentials, Auditory, Brain Stem/de [Drug Effects];*Evoked Potentials, Somatosensory/de [Drug Effects];Female;Follow-Up Studies;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Magnetic Resonance Imaging;Male;Monitoring, Physiologic;Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];Prospective Studies;Time Factors;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Grimm, G.;Oder, W.;Prayer, L.;Ferenci, P.;Madl, C.",1990,Oct 20,,0,0,
709,Is Wilson's disease a dementing condition?,"A case presentation in this journal by Rosselli, Lorenzana, Lasselli and Vergara (1981) has raised the issue of intellectual deterioration in Wilson's Disease. Relevant findings in the recent literature are discussed.",*Dementia/px [Psychology];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/px [Psychology];Humans;*Neuropsychological Tests;Penicillamine/tu [Therapeutic Use];Wechsler Scales;GNN1DV99GX (Penicillamine),"Lang, C.",1989,Aug,https://dx.doi.org/10.1080/01688638908400914,0,0,
710,"Wilson's disease: an update, with emphasis on new approaches to treatment",,Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration;Humans;Molybdenum/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Pregnancy;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Brewer, G. J.;Yuzbasiyan-Gurkan, V.",1989,,,0,0,
711,Wilson's disease,"Wilson's disease, an autosomal recessive disorder of copper metabolism, most often becomes apparent in adolescence and may present with a multitude of signs and symptoms. Early diagnosis and treatment can prevent irreversible damage to the liver and the central nervous system. The diagnosis is confirmed by hepatic biopsy and quantitation of copper in the tissues. Treatment is chelation of excess copper. If untreated, Wilson's disease is fatal. [References: 25]",Adolescent;Adult;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration;Humans;Male;Penicillamine/tu [Therapeutic Use];Pregnancy;GNN1DV99GX (Penicillamine),"Woods, S. E.;Colon, V. F.",1989,Jul,,0,0,
712,[Copper],"Copper is an indispensable trace element for life. Four points are fundamental: copper is combined with essential enzymatic systems (oxidases, transaminases), copper is necessary for inclusion of iron in the molecule of hemoglobin, copper has a primordial role in the metabolism of molecule of hemoglobin, copper has a primordial role in the metabolism of collagen and elastin and some vascular diseases (aneurysms) are closely related to its lack, finally, there is an increase of plasmatic copper during cancerous diseases, which is significant even at an early time and usually proportional to the evolution. [References: 126]","Anemia, Hypochromic/et [Etiology];Animals;Collagen/me [Metabolism];Copper/bl [Blood];Copper/df [Deficiency];Copper/me [Metabolism];*Copper/ph [Physiology];Elastin/me [Metabolism];Hepatolenticular Degeneration/me [Metabolism];Humans;Menkes Kinky Hair Syndrome/me [Metabolism];Mice;Neoplasms/bl [Blood];Rabbits;Zinc/ph [Physiology];789U1901C5 (Copper);9007-34-5 (Collagen);9007-58-3 (Elastin);J41CSQ7QDS (Zinc)","Elkoubi, P.",1989,Apr,,0,0,
713,Fulminant hepatic failure without evidence of cirrhosis in a case of Wilson's disease,"We treated a sixteen-year old Japanese girl with fulminant hepatic failure in Wilson's disease. The diagnosis of Wilson's disease was made immediately after the admission because of low serum copper and ceruloplasmin levels with high urinary copper excretion. Her hepatic failure was accompanied by bouts of hemolytic crisis. In spite of the administration of D-penicillamine and repeated plasmapheresis, she died of hepatic failure four months later. At autopsy, the surface of the liver was smooth. The histology of the liver showed massive necrosis. There were only a few remaining scattered hepatocytes, in which copper was revealed by Rhodanine staining. There was no evidence of cirrhosis. The livers of the previously reported cases of Wilson's disease accompanied by fulminant hepatic failure were all cirrhotic. Our case indicated that Wilson's disease could occur as true fulminant hepatic failure without preceeding neurological and hepatological signs and the evidence of cirrhosis. [References: 16]",Adolescent;Atrophy;Combined Modality Therapy;Female;*Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/th [Therapy];Humans;*Liver/pa [Pathology];Necrosis;Penicillamine/tu [Therapeutic Use];Plasmapheresis;GNN1DV99GX (Penicillamine),"Enomoto, K.;Ishibashi, H.;Irie, K.;Okumura, Y.;Nomura, H.;Fukushima, M.;Inaba, S.;Niho, Y.",1989,Jan-Feb,,0,0,
714,Wilson's disease presenting with features of hepatic dysfunction: a clinical analysis of eighty-seven patients,"An analysis has been made of presenting symptoms and course in 87 patients with predominantly hepatic Wilson's disease. In 30 patients, in whom the diagnosis was made relatively quickly, response to treatment was excellent and all recovered although two had severe haemolytic crises. Mean age of onset was 11 years (range five to 22). Nine patients suffered toxic reactions to penicillamine and were then treated with trientine. In 22 patients the diagnosis was made after neurological symptoms had supervened; in 20 the signs of hepatic damage had disappeared despite the lack of treatment but in two hepatic signs persisted until the central nervous system was affected. In the 20 patients in whom signs of liver disease resolved spontaneously there was a time interval of from one to eight years before neurological signs developed. All 22 patients in a third group died of hepatic disease without central nervous system involvement. In 19 cases duration of the illness was brief and the diagnosis was made very late or at post-mortem examination. One patient survived with chronic progressive liver damage for 20 years; diagnosis was also made at post-mortem examination. Mean age at death was 15 years. The diagnosis was made retrospectively in 13 patients who died. In two of these the diagnosis was confirmed by determination of the liver copper concentration on tissue saved at postmortem examination; in the other 11 the diagnosis is probable since other siblings developed a similar illness, proven to be Wilson's disease. Age range for these patients was eight to 13 years. Duration of the illness from onset to death was nine days to four years (mean 10 weeks). There was no example of primary carcinoma of the liver in this series.",Adolescent;Child;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/mo [Mortality];Humans;Liver Function Tests;Male;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Walshe, J. M.",1989,Mar,,0,0,
715,Treatment of Wilson's disease with zinc. VI. Initial treatment studies,"Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.","Acetates/tu [Therapeutic Use];Acetic Acid;Alanine Transaminase/bl [Blood];Aspartate Aminotransferases/bl [Blood];Biopsy, Needle;Copper/bl [Blood];Copper/to [Toxicity];Copper/ur [Urine];Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/de [Drug Effects];Metallothionein/me [Metabolism];Time Factors;*Zinc/tu [Therapeutic Use];0 (Acetates);789U1901C5 (Copper);9038-94-2 (Metallothionein);EC 2-6-1-1 (Aspartate Aminotransferases);EC 2-6-1-2 (Alanine Transaminase);J41CSQ7QDS (Zinc);Q40Q9N063P (Acetic Acid)","Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Lee, D. Y.;Appelman, H.",1989,Dec,,0,0,
716,Zinc treatment of Wilson's disease,,Animals;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/de [Drug Effects];Liver/me [Metabolism];Metallothionein/me [Metabolism];*Zinc/tu [Therapeutic Use];0 (copper thionein);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc),"Sandstead, H. H.",1989,Dec,,0,0,
717,Sulphasalazine in rheumatoid arthritis: haematological problems,,"*Arthritis, Rheumatoid/dt [Drug Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];*Sulfasalazine/tu [Therapeutic Use];3XC8GUZ6CB (Sulfasalazine);GNN1DV99GX (Penicillamine)","Lyle, W. H.",1989,Aug,,0,0,
718,D-penicillamine-induced elastosis perforans serpiginosa in a child with juvenile rheumatoid arthritis. Report of a case and review of the literature,"Elastosis perforans serpiginosa is a rare complication of D-penicillamine therapy. It has been reported to occur in Wilson's disease and cystinuria, usually after many years of high-dose therapy. We report a case of D-penicillamine-induced elastosis perforans serpiginosa with unique clinical features occurring in a 10-year-old child with juvenile rheumatoid arthritis who received only 71 gm of the drug over 9 months. The case is also unusual because of the short course and low cumulative dose of drug received and because of the calcification of elastic fibers. The calcification of elastic fibers suggests that this case may represent an unusual variant of elastosis perforans serpiginosa or an overlap with pseudoxanthoma elasticum. All reported cases of D-penicillamine-induced elastosis perforans serpiginosa are reviewed, and histopathologic and electron microscopic findings are presented. The theoretic mechanisms of action of D-penicillamine on elastic tissue synthesis and morphology are discussed. [References: 18]","*Arthritis, Juvenile/dt [Drug Therapy];Child;*Drug Eruptions/et [Etiology];Drug Eruptions/pa [Pathology];*Elastic Tissue/de [Drug Effects];Elastic Tissue/ul [Ultrastructure];Female;Humans;Microscopy, Electron;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Sahn, E. E.;Maize, J. C.;Garen, P. D.;Mullins, S. C.;Silver, R. M.",1989,May,,0,0,
719,"Treatment of Wilson's disease with zinc. V. Changes in serum levels of lipase, amylase, and alkaline phosphatase in patients with Wilson's disease","We noted a frequent increase in the serum enzymes amylase, lipase, and alkaline phosphatase in patients with Wilson's disease who are receiving zinc acetate therapy (25 or 50 mg elemental zinc three times daily). Typically, values are normal before the initiation of zinc therapy, increase to slightly above normal after a few weeks of therapy, and stabilize at the high normal range after approximately a year of treatment. Very large dosages of zinc (800 mg/day) produce even further elevation of serum lipase and amylase without the symptoms of pancreatitis. Pancreatic pathologic studies of a zinc-treated rat model receiving dosages equivalent to up to 25 times the effective dosage in a human being, which is based on milligrams of zinc per kilogram of body weight, reveal that no lesions are induced by zinc treatment in the pancreas. We interpret these findings to indicate that extended maintenance therapy with zinc does not pose a risk of pancreatic damage in patients with Wilson's disease.","Adolescent;Adult;*Alkaline Phosphatase/bl [Blood];*Amylases/bl [Blood];Animals;Disease Models, Animal;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lipase/bl [Blood];Male;Middle Aged;Pancreas/pa [Pathology];Rats;Rats, Inbred Strains;*Zinc/tu [Therapeutic Use];EC 3-1-1-3 (Lipase);EC 3-1-3-1 (Alkaline Phosphatase);EC 3-2-1 (Amylases);J41CSQ7QDS (Zinc)","Yuzbasiyan-Gurkan, V.;Brewer, G. J.;Abrams, G. D.;Main, B.;Giacherio, D.",1989,Nov,,0,0,
720,Successful long term oral zinc in florid Wilson's disease: a case report,"We describe the clinical course of a patient with florid, predominantly neurological, Wilson's disease who developed serious toxic effects of d-penicillamine therapy but responded well to long term oral zinc sulphate. A congenital portosystemic shunt has decompressed the portal bed adequately to prevent the development of varices. We also documented the return to normal of a grossly abnormal pancreolauryl test after withdrawal of zinc.","Administration, Oral;Adolescent;Copper/ur [Urine];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;India;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Sulfates/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Kaur, U.;Bambery, P.;Bhushnurmath, S. R.;Deodhar, S. D.;Dilawari, J. B.",1988,Apr,,0,0,
721,Drug therapy in Wilson's disease,,*Ethylenediamines/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);SJ76Y07H5F (Trientine),"Reed, K.",1988,Jun,,0,0,
722,Neuropathological findings in penicillamine-treated patients with Wilson's disease,"We report the terminal neurological impairment, amount of penicillamine taken, neuropathology and cerebral copper content of eleven patients with Wilson's disease treated for as long as 17 years. Therapy was accompanied by complete resolution of neurologic symptomatology in five patients and significant improvement in the neuro-psychiatric manifestations in six. Abnormal glial cells were seen in all the brains; gross or micro-cavitary changes were present in the putamina of eight. Of the four sets of observations, there was virtually no correlation between the degree of neurologic dysfunction - if any - in the months before death and either the amount of penicillamine taken or the cerebral copper content. There was, however, a fair degree of correlation between the severity of the neuropathologic findings and cerebral copper content.",Adult;Brain Chemistry;Copper/an [Analysis];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Middle Aged;*Penicillamine/tu [Therapeutic Use];*Putamen/pa [Pathology];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Horoupian, D. S.;Sternlieb, I.;Scheinberg, I. H.",1988,Mar-Apr,,0,0,
723,Wilson's disease in The Merck Manual: corrections,,Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];Pregnancy;Zinc/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Berkow, R.",1988,May 27,,0,0,
724,Zinc therapy as the initial treatment for Wilson's disease,,"Administration, Oral;Drug Administration Schedule;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Sulfates/ad [Administration & Dosage];Sulfates/ae [Adverse Effects];*Sulfates/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];Zinc/ae [Adverse Effects];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Hoogenraad, T. U.;Van Hattum, J.",1988,Apr,,0,0,
725,Wilson's disease,,*Hepatolenticular Degeneration/ci [Chemically Induced];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Zinc/ae [Adverse Effects];Zinc/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Pfeiffer, C. C.;Camo, B.",1988,Mar,,0,0,
726,[Hepatocerebral dystrophy in pregnancy],,Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;*Penicillamine/tu [Therapeutic Use];*Pregnancy/de [Drug Effects];Pregnancy/ph [Physiology];*Pregnancy Complications/dt [Drug Therapy];Pregnancy Complications/pp [Physiopathology];GNN1DV99GX (Penicillamine),"Shekhtman, M. M.;Koridze, R. S.",1988,Oct,,0,0,
727,Does CSF copper level in Wilson disease reflect copper accumulation in the brain?,"The levels of copper and ceruloplasmin in the cerebrospinal fluid (CSF) of patients with Wilson disease were investigated. Ceruloplasmin concentrations in the CSF of all patients were almost the same but were lower than those of the controls. CSF copper concentrations in patients without neurologic signs were within the normal range, 22 +/- 6 ng/ml. In contrast, CSF copper concentrations in patients with neurologic signs (69-98 ng/ml) were significantly higher than the normal levels before and at the beginning of the treatment with D-penicillamine; it gradually decreased in response to treatment. These results suggest that the appearance of neurologic manifestations in Wilson disease is not related to the CSF ceruloplasmin concentration. The CSF copper concentration in this disease appears to reflect copper accumulation in the brain and may be useful as a marker for monitoring therapy.","Adolescent;*Brain/me [Metabolism];Child;Child, Preschool;Copper/cf [Cerebrospinal Fluid];*Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/cf [Cerebrospinal Fluid];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;789U1901C5 (Copper)","Kodama, H.;Okabe, I.;Yanagisawa, M.;Nomiyama, H.;Nomiyama, K.;Nose, O.;Kamoshita, S.",1988,Jan-Feb,,0,0,
728,Pregnancy in a woman with Wilson's disease treated with zinc,,Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Pregnancy;*Pregnancy Complications/dt [Drug Therapy];*Sulfates/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);J41CSQ7QDS (Zinc),"Lao, T. T.;Chin, R. K.;Cockram, C. S.;Leung, N. W.",1988,Jun,,0,0,
729,Wilson's disease in south India and experience with zinc therapy,,"Administration, Oral;Adolescent;Adult;Child;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;India;Male;Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc)","Murthy, B. S.;Murthy, J. M.;Krishnaveni, A.;Reddy, M. V.;Das, S. M.",1988,Jul,,0,0,
730,Wilson's disease associated with pancreatitis,"A 12-year-old boy presented with a 2-month history of abdominal pain and distention. A diagnosis of Wilson's disease was established, and D-penicillamine therapy was initiated. An associated pancreatitis was diagnosed on presentation, based on elevated serum amylase and an enlarged pancreas ultrasonically. Subsequently, an 18-month follow-up disclosed no abdominal pain, with repeatedly normal serum amylase level and a normal pancreas on ultrasonography. Since abdominal pain is a common symptom in Wilson's disease on presentation, this possibility should be considered in untreated patients. It is concluded that pancreatitis may be associated with Wilson's disease, possibly because of copper deposition in the pancreas, and is probably responsive to copper chelation therapy.",Acute Disease;Child;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Pancreatitis/co [Complications];Pancreatitis/dt [Drug Therapy];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Weizman, Z.;Picard, E.;Barki, Y.;Moses, S.",1988,Nov-Dec,,0,0,
731,Management of an oroantral fistula in a patient with Wilson's disease: case report and review of the literature,"After removal of an impacted maxillary third molar, an oroantral fistula developed in a patient with Wilson's disease. Management consisted of antibiotics, decongestants, irrigation, and surgical closure. Complications of treatment did not directly involve the disease but, rather, were related to the therapeutic agent penicillamine. Penicillamine causes interference between the cross links of tropocollagen molecules and cleaves newly formed molecules. Reduction in dosage is recommended when surgery is planned to increase collagen formation and, thus, healing. Such a measure was undertaken in this case. The patient healed uneventfully. A review of Wilson's disease and a case report are presented. [References: 37]","Adult;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Molar, Third/su [Surgery];Oroantral Fistula/et [Etiology];*Oroantral Fistula/su [Surgery];Penicillamine/ae [Adverse Effects];Streptococcal Infections/co [Complications];Tooth Extraction/ae [Adverse Effects];Tooth, Impacted/su [Surgery];GNN1DV99GX (Penicillamine)","Greene, M. W.;King, R. C.;Alley, R. S.",1988,Sep,,0,0,
732,"Wilson's disease: yesterday, today, and tomorrow",,"Brain/dg [Diagnostic Imaging];Brain/pa [Pathology];Female;Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/hi [History];History, 20th Century;Humans;Male;Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Walshe, J. M.",1988,,https://dx.doi.org/10.1002/mds.870030104,0,0,
733,Lid-opening apraxia in Wilson's disease,"A student was diagnosed as having Wilson's disease only after the severe, intermittent inability to open his eyes led him to seek neurologic evaluation. Although lid-opening apraxia is usually a symptom of diffuse extrapyramidal disease, it has not previously been reported in Wilson's disease.",Adult;*Apraxias/et [Etiology];Atrophy;Brain/dg [Diagnostic Imaging];Cerebellum/dg [Diagnostic Imaging];*Eyelid Diseases/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];Radiography;GNN1DV99GX (Penicillamine),"Keane, J. R.",1988,Mar,,0,0,
734,[An unusual cutaneous reaction pattern as a side effect of penicillamine: elastosis perforans serpiginosa],,Adult;Cystinuria/dt [Drug Therapy];*Drug Eruptions/et [Etiology];Drug Eruptions/pa [Pathology];*Elastic Tissue/pa [Pathology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"van Joost, T.;de Leeuw, J.",1988,Mar 12,,0,0,
735,Diagnosis and treatment of presymptomatic Wilson's disease,"In ninety families with at least one proven case of Wilson's disease, seen over 32 years, all close relatives were examined and ""presymptomatic"" disease was diagnosed in 30. 11 had one or more abnormal physical signs when examined and 7 of these had Kayser Fleischer rings. In a further 10 patients the abnormalities of copper metabolism were so pronounced as to leave no doubt as to the diagnosis. 6 patients were not seen until they had been on treatment for 2 years or more; in some, much of the evidence on which the diagnosis was based is not available. In 3 patients there were only minor histological abnormalities in the liver and no increase in urinary copper but other indices of copper metabolism pointed to a diagnosis of Wilson's disease. 2 patients had transient neurological signs after starting treatment; otherwise, all but one (who died in an accident) have remained well for up to 26 years.",Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Child;Copper/me [Metabolism];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver/pa [Pathology];Male;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Walshe, J. M.",1988,Aug 20,,0,0,
736,Clinical assessment of 31 patients with Wilson's disease. Correlations with structural changes on magnetic resonance imaging,"Thirty-one patients with Wilson's disease were evaluated with detailed neurologic and medical examinations. Mean age (+/- SD) at onset was 21 +/- 5 years and at examination was 28 +/- 6 years. Of the 90% of patients who were first treated with penicillamine, 31% deteriorated initially despite therapy, and half never recovered to pretherapy baseline. At the time of our evaluations, the most common neurologic findings were dysarthria (97%), dystonia (65%), dysdiadochokinesia (58%), rigidity (52%), gait and postural abnormalities (42%), and tremor (32%). Chorea and dementia were rare. Twenty-two patients underwent magnetic resonance imaging. All but one of the 19 symptomatic patients had abnormal scans. The three asymptomatic patients had normal scans. Most lesions were seen in the caudate, putamen, subcortical white matter, midbrain, and pons. Generalized brain atrophy was also common. Lesions were less common in the thalamus, cerebellar vermis, midbrain tegmentum, globus pallidus, red nucleus, and dentate nucleus. Dystonia and bradykinesia correlated with putamen lesions, and dysarthria correlated with both putamen and caudate lesions.",Adolescent;Adult;*Brain/pa [Pathology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Magnetic Resonance Spectroscopy;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Prednisone/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);VB0R961HZT (Prednisone),"Starosta-Rubinstein, S.;Young, A. B.;Kluin, K.;Hill, G.;Aisen, A. M.;Gabrielsen, T.;Brewer, G. J.",1987,Apr,,0,1,
737,Management of Wilson's disease with zinc sulphate. Experience in a series of 27 patients,"Evaluation of the literature concerning the various approaches for the treatment of Wilson's disease led to the conclusion that zinc sulphate might be a good choice because it is effective and relatively safe. Twenty seven patients were managed with zinc sulphate for a total period of 142 patients-years. The drug was administered in doses varying from 300 to 1200 mg/day. Of the 9 patients who were treated with zinc from the start, 8 improved and one died from severe cirrhosis. All 8 patients who were placed on zinc after intolerance to penicillamine did well on zinc therapy. Ten patients were changed to zinc after they had first been treated with penicillamine without developing signs of intolerance. Of this group 8 patients were kept on long-term zinc therapy, 2 were changed back to penicillamine because of personal preference. Signs of intolerance to zinc were not observed. All patients kept a diet containing about 1.2 mg of copper a day. Our experience supports the idea that zinc sulphate is a good choice for the treatment of Wilson's disease: the drug is effective, safe and cheap.",Copper/bl [Blood];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Sulfates/tu [Therapeutic Use];Zinc/bl [Blood];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Hoogenraad, T. U.;Van Hattum, J.;Van den Hamer, C. J.",1987,Feb,,0,1,
738,Systemic sclerosis-like lesions during long-term penicillamine therapy for Wilson's disease,"Systemic sclerosis-like lesions developed in a 14-year-old boy with Wilson's disease who had been treated with D-penicillamine for 11 years. Clinical and laboratory manifestations included proximal scleroderma, pulmonary restrictive defects, positive antinuclear antibodies, and the deposition of C3 at the dermal-epidermal junction of the lesional skin. This is the first case reported in which long-term administration of penicillamine was followed by the development of systemic sclerosis-like lesions.","Adolescent;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Scleroderma, Systemic/ci [Chemically Induced];Scleroderma, Systemic/pa [Pathology];GNN1DV99GX (Penicillamine)","Miyagawa, S.;Yoshioka, A.;Hatoko, M.;Okuchi, T.;Sakamoto, K.",1987,Jan,,0,0,
739,D-penicillamine induced dermopathy in Wilson's disease,,Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];*Skin Diseases/ci [Chemically Induced];GNN1DV99GX (Penicillamine),"Dootson, G.;Sarkany, I.",1987,Jan,,0,0,
740,CSF copper concentration: a new parameter for diagnosis and monitoring therapy of Wilson's disease with cerebral manifestation,"In five patients with cerebral manifestation of Wilson's disease, copper was measured in CSF, serum, urine and liver, and ceruloplasmin was determined in CSF and serum. CSF copper was found to be elevated in all cases, especially in the four examined before therapy. Two patients were followed up for a period of 3 years, while undergoing therapy with chelating substances. In case 1, the data and the clinical course are presented in detail: prior to therapy, the daily urinary copper excretion had been elevated, and this increased during the initial treatment stages. The serum copper concentration, which was already low, decreased quickly the during the initial stages of therapy, and remained at a low level during further treatment. In contrast to its level in serum, the copper level in the CSF was up to 3-fold the normal range and fell only very slowly as clinical symptoms improved. These findings suggest transport of copper from the CNS to the CSF. The copper concentration in CSF appears to be a valuable parameter for diagnosis and monitoring therapy in patients with cerebral manifestation of Wilson's disease.","Adult;*Brain Diseases, Metabolic/cf [Cerebrospinal Fluid];Brain Diseases, Metabolic/et [Etiology];Copper/bl [Blood];*Copper/cf [Cerebrospinal Fluid];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/cf [Cerebrospinal Fluid];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Weisner, B.;Hartard, C.;Dieu, C.",1987,Jun,,0,0,
741,The use of trientine in preventing the effects of interrupting penicillamine therapy in Wilson's disease,"Penicillamine is known to be effective therapy for Wilson's disease. However, the clinical consequences of the abrupt and permanent withdrawal of penicillamine have not been investigated. We studied 11 patients who stopped their own treatment after having been treated successfully with penicillamine (1 to 2 g per day) for periods of 3 to 19 years. Eight died of hepatic decompensation or fulminant hepatitis after an average survival of only 2.6 years. In another 13 patients, penicillamine was discontinued by the physician because of serious adverse reactions. In these patients, penicillamine was replaced with trientine (1 to 1.5 g per day), a newer chelating agent. All but one of these patients (who was killed accidentally) are alive at this writing, from 2 to 15 years later. Our observations suggest that discontinuation of penicillamine in patients with Wilson's disease results in rapid clinical deterioration, which is often fatal. The replacement of penicillamine with trientine appears to prevent this adverse clinical course.",*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/mo [Mortality];Humans;Male;Middle Aged;Patient Compliance;*Penicillamine/ae [Adverse Effects];*Substance Withdrawal Syndrome/dt [Drug Therapy];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Scheinberg, I. H.;Jaffe, M. E.;Sternlieb, I.",1987,Jul 23,https://dx.doi.org/10.1056/NEJM198707233170405,0,1,
742,"Wilson's disease, a reversible dementia: case report","A case of advanced Wilson's disease with clear dementing features is presented. Neuropsychological evaluation before treatment revealed intellectual deterioration particularly in memory and performance tasks. The patient was treated with Penicillamine, a copper-chelating agent, for 7 months, with notable improvement in her dementia and in her motor signs. A second battery of neuropsychological tests demonstrated the improvement in the mental aspects. These findings support the concept of Wilson's disease being a reversible dementia.","Adult;*Dementia/di [Diagnosis];Dementia/dt [Drug Therapy];Dementia/px [Psychology];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Humans;Neuropsychological Tests;Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Rosselli, M.;Lorenzana, P.;Rosselli, A.;Vergara, I.",1987,Aug,https://dx.doi.org/10.1080/01688638708405060,0,0,
743,Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy,"We describe a patient with Wilson's disease who presented with neurologic disease, was treated with D-penicillamine, and suffered sudden neurologic deterioration coincident with therapy. Replicate brain magnetic resonance imaging examinations after six weeks and 11 months of penicillamine therapy documented the development of new brain lesions during this period, while liver biopsy specimen data disclosed that excellent hepatic decoppering had occurred. To develop information on the relative rarity or frequency of neurologic worsening with the initiation of penicillamine therapy, we conducted a retrospective survey of 25 additional patients with Wilson's disease who met the criteria of presenting with neurologic disease and having been treated with penicillamine. The replies indicate that, at least from the patient's viewpoint, this syndrome occurs frequently. We suggest that the cause of this distressing syndrome, and ways to mitigate or circumvent it, must be discovered.",Adolescent;Adult;Basal Ganglia/pa [Pathology];Female;Frontal Lobe/pa [Pathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Magnetic Resonance Spectroscopy;Male;Middle Aged;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Retrospective Studies;Seizures/ci [Chemically Induced];Zinc/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Brewer, G. J.;Terry, C. A.;Aisen, A. M.;Hill, G. M.",1987,May,,0,0,
744,Treatment of Wilson's disease with zinc: III. Prevention of reaccumulation of hepatic copper,"Twelve patients with Wilson's disease, most of whom had received intensive treatment with penicillamine, were given zinc therapy as their sole medication for copper control. Serial liver biopsies were performed during a 12- to 20-month follow-up period to determine whether hepatic copper reaccumulates during zinc therapy. Mean baseline liver copper concentration was 255 micrograms/gm dry weight, whereas the mean value after therapy was 239 micrograms. No patient demonstrated hepatic reaccumulation of copper during zinc therapy. Copper balance, 24-hour urinary copper excretion, and nonceruloplasmin plasma copper concentration all indicated good copper control during zinc therapy. Hepatic zinc concentration increased twofold to threefold over baseline values but no toxicity was seen. Hepatic zinc concentrations appeared to reach a plateau after 12 to 18 months of zinc therapy. We conclude that oral zinc as the sole maintenance therapy in patients with Wilson's disease prevents hepatic reaccumulation of copper.",*Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;*Liver/me [Metabolism];Zinc/me [Metabolism];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Brewer, G. J.;Hill, G. M.;Dick, R. D.;Nostrant, T. T.;Sams, J. S.;Wells, J. J.;Prasad, A. S.",1987,May,,0,0,
745,Zinc-copper interaction provides a novel and apparently effective alternative therapy for Wilson's disease,,*Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Sandstead, H. H.",1987,May,,0,0,
746,Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens,"The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance.",Adult;Copper/me [Metabolism];Drug Administration Schedule;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Middle Aged;*Zinc/ad [Administration & Dosage];Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Hill, G. M.;Brewer, G. J.;Prasad, A. S.;Hydrick, C. R.;Hartmann, D. E.",1987,May-Jun,,0,0,
747,The treatment of Wilson's disease with zinc. IV. Efficacy monitoring using urine and plasma copper,"Progress has been made in establishing the efficacy and safety of oral zinc as a maintenance therapy for Wilson's disease. It is important to develop simple, noninvasive monitoring methods to assure the adequacy of zinc therapy in individual patients. In this paper we report the use of 24-hr urine copper and plasma copper measurements to monitor efficacy of zinc maintenance therapy in 30 Wilson's disease patients. In examples of therapeutic inadequacy such as noncompliance, these values increase. With continued long-term adequate therapy, they remain stable or decrease. These two simple monitoring tools appear to be very useful in monitoring Wilson's disease patients receiving zinc therapy.",Ceruloplasmin/an [Analysis];*Copper/bl [Blood];Copper/ur [Urine];Follow-Up Studies;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];In Vitro Techniques;Penicillamine;*Zinc/tu [Therapeutic Use];Zinc/ur [Urine];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Brewer, G. J.;Hill, G.;Prasad, A.;Dick, R.",1987,Apr,,0,0,
748,Neurological abnormalities in Wilson's disease are reversible,"The therapeutic responses of seven children with Wilson's disease who presented with neurological disease were evaluated. Neurological abnormalities comprised intellectual deterioration in 7, conduct disorder in five, dystonia in three, choreoathetosis in three, seizures in one and hemiparesis in one. Lethargy and weight loss were present for several months in 6 children. Four children had clinically demonstrable liver disease which was fatal in two. Electroencephalography performed in two children was normal. Computed tomography (CT) of the brain in three children showed cerebral atrophy in all and areas of low attenuation in the basal ganglia which resolved on treatment in one. All patients were treated with penicillamine but, in four, triethylene tetramine (TETA) was substituted because of adverse effects. Neurological abnormalities in these patients were reversible.",Adolescent;Child;Child Behavior Disorders/pc [Prevention & Control];*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/px [Psychology];Humans;Intelligence;Male;*Penicillamine/tu [Therapeutic Use];Seizures/pc [Prevention & Control];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Lingam, S.;Wilson, J.;Nazer, H.;Mowat, A. P.",1987,Feb,https://dx.doi.org/10.1055/s-2008-1052427,0,1,
749,Wilson's disease: varied manifestations and consequences of non-compliance with treatment,,Adult;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Humans;Male;*Patient Compliance;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Breen, E.;Tolan, M.;Meaney, J.;Lucey, C.;McCarthy, C.;O'Gorman, T.",1987,Dec,,0,0,
750,Treatment of Wilson's disease,,*Copper/me [Metabolism];*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Pregnancy;*Trientine/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];0 (Ethylenediamines);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Young, A. B.",1987,Jun,https://dx.doi.org/10.1055/s-2008-1041420,0,0,
751,Hepatic copper and metallothionein distribution in Wilson's disease (hepatolenticular degeneration),"Wilson's disease is a rare inherited disorder of copper (Cu) metabolism characterized by the deposition of Cu in the liver, brain, and cornea. The levels of metallothionein (MT), Cu, and zinc (Zn) in the livers of two Wilson's disease patients were analyzed in this study. About 50-fold increase in the Cu levels above normal controls was observed in both patients (160 and 298 micrograms/g of wet tissue). About 73% of subcellular Cu was present in the cytoplasmic fraction and most of it was in association with MT. Analysis of hepatic MT levels showed a 3-fold increase (863 micrograms/g of wet tissue) over control human levels (321 micrograms/g of wet tissue). The two forms of MT (MT-I and MT-II) were isolated from one liver sample. Both forms contained high amounts of Cu (11 to 12 g atoms/mole), indicating saturation of MT which had only 2 to 3 g atoms of zinc. The distribution of MT in the hepatocytes was investigated using an immunohistochemical method. In tissue sections with minimal tissue damage, there was intense cytoplasmic staining for MT in hepatocytes whereas both nuclear and cytoplasmic staining was found in tissue sections with extensive necrosis and fibrosis. These results suggest that MT is the major hepatic Cu-binding protein in Wilson's disease, that it is present in a form saturated with Cu, and that only in degenerating hepatocytes is it found in the nucleus as well as the cytoplasm.",Adult;Child;*Copper/me [Metabolism];Cytoplasm/me [Metabolism];*Hepatolenticular Degeneration/me [Metabolism];Humans;Immunoenzyme Techniques;*Liver/me [Metabolism];Male;*Metallothionein/me [Metabolism];Zinc/me [Metabolism];789U1901C5 (Copper);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc),"Nartey, N. O.;Frei, J. V.;Cherian, M. G.",1987,Oct,,0,0,
752,Hemolytic anemia with jaundice and ascites,,"Adult;*Anemia, Hemolytic/co [Complications];Ascites/co [Complications];Copper/ur [Urine];Diagnosis, Differential;Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Jaundice/co [Complications];Liver/pp [Physiopathology];Liver Function Tests;Penicillamine/tu [Therapeutic Use];Prothrombin Time;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Jeffers, L.",1987,May 30,,0,0,
753,Penicillamine may detoxify copper in Wilson's disease,,"*Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Inactivation, Metabolic;*Penicillamine/pd [Pharmacology];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Scheinberg, I. H.;Sternlieb, I.;Schilsky, M.;Stockert, R. J.",1987,Jul 11,,0,0,
754,"Wilson's disease in the Commonwealth of Dominica, a case report","The first case reported in Dominica of Wilson's disease is described. This is possibly the first successfully treated case in the West Indies. Wilson's disease, though rare, may occur in an unexpected setting.",Adolescent;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration;Humans;Male;Pedigree;Penicillamine/tu [Therapeutic Use];West Indies;GNN1DV99GX (Penicillamine),"Cooles, P.;Khosla, D.;Brathwaite, A.",1986,Mar,,0,0,
755,Detection of Wilson's disease in sibs of a patient with Wilson's disease,,Copper/me [Metabolism];*Copper/ur [Urine];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Penicillamine/me [Metabolism];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Kamoun, P.;Cadoudal, M.;Rabier, D.;Jerome, H.",1986,Feb,,0,0,
756,Penicillamine associated pulmonary hemorrhage,"Penicillamine is the drug of choice in Wilson's disease and a therapeutic alternative in rheumatoid arthritis. Autoimmune complications associated with penicillamine include cases resembling systemic lupus erythematosus and Goodpasture's syndrome. We report a case of diffuse pulmonary hemorrhage associated with prolonged penicillamine use in a patient with Wilson's disease with evidence of circulating immune complexes and complement activation, but without serologic or morphologic evidence of systemic lupus erythematosus, Goodpasture's syndrome or renal disease.",Adult;Antigen-Antibody Complex/im [Immunology];*Hemorrhage/ci [Chemically Induced];Hemorrhage/im [Immunology];Hemorrhage/pa [Pathology];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lung Diseases/ci [Chemically Induced];Lung Diseases/im [Immunology];Lung Diseases/pa [Pathology];Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];0 (Antigen-Antibody Complex);GNN1DV99GX (Penicillamine),"Louie, S.;Gamble, C. N.;Cross, C. E.",1986,Oct,,0,0,
757,Reversible pancytopenia secondary to treatment with tetrathiomolybdate,,Adult;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Molybdenum/ae [Adverse Effects];*Pancytopenia/ci [Chemically Induced];81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Harper, P. L.;Walshe, J. M.",1986,Dec,,0,0,
758,Treatment of Wilson's disease with zinc. II. Validation of oral 64copper with copper balance,"The efficacy of zinc as a therapeutic agent to control copper balance in Wilson's disease patients has been previously documented with balance studies. In an attempt to develop a simpler and faster tool for evaluating the adequacy of zinc therapy, a technique that measures the uptake into blood of a small oral dose of 64copper was studied in conjunction with copper balance. The mean peak 64copper uptake into blood of nine Wilson's disease patients on D-penicillamine, trien, or no medication was 6.04 +/- 2.74%, comparable with normal controls. Seven patients on zinc therapy had a markedly and significantly reduced mean uptake of 0.79 +/- 1.05% after treatment. The data demonstrate that the prevention of copper uptake into blood in Wilson's disease patients by zinc therapy can be evaluated by 64copper uptake and that peak uptakes of less than 1% occur in patients with neutral or negative copper balance.",Acetates/tu [Therapeutic Use];Acetic Acid;Adult;*Copper/me [Metabolism];Drug Evaluation;*Hepatolenticular Degeneration/dt [Drug Therapy];Homeostasis;Humans;Radioisotopes;Sulfates/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Acetates);0 (Radioisotopes);0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);J41CSQ7QDS (Zinc);Q40Q9N063P (Acetic Acid),"Hill, G. M.;Brewer, G. J.;Juni, J. E.;Prasad, A. S.;Dick, R. D.",1986,Dec,,0,1,
759,"[Copper-binding proteins in liver, kidney and brain tissue from a Wilson's disease patient]","Copper-binding proteins (Cu-PBs) in the liver, kidney, and brain tissues from a Wilson's disease patient, who was 19-year-old woman and died of hemolytic crisis, were examined with Sephadex G-75 gel chromatography and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Copper contents, which were determined by flameless atomic absorption spectrophotometry in the liver, kidney, and cerebral tissues from the patient, were 28-, 38-, and 3.5-fold, respectively, as compared to those of control subject, who was 5-year-old girl and died of cerebral palsy. Each tissue was homogenized in 3 volumes of 50 mM Tris-HCl buffer, pH 8.6, and the homogenate was centrifuged at 105,000 g for 60 min to obtain cytosol fraction. Sephadex G-75 gel chromatography of cytosols from Wilson's liver and kidney showed that most of increased copper existed as Cu-thionein (Cu-Th), in contrast to a much lower Cu-Th level in control liver cytosol and to no detectable amount of Cu-Th in control kidney cytosol. In addition, Zn-Th was also increased in Wilson's kidney cytosol, while it was decreased in Wilson's liver cytosol. Gel chromatography of Wilson's cerebral cytosol revealed that the increased copper bound mainly to two proteins with apparent molecular mass of 10 kDa (Cu-BP 1) and 20 kDa (Cu-BP 2), respectively, both of which showed no absorption at 280 nm and were not observed in control cerebral cytosol even after addition of excess copper (50 micrograms/ml) as CuSO4.(ABSTRACT TRUNCATED AT 250 WORDS)","Adult;*Brain Chemistry;*Carrier Proteins/an [Analysis];Child, Preschool;Chromatography, Gel;Electrophoresis, Polyacrylamide Gel;Female;*Hepatolenticular Degeneration/me [Metabolism];Humans;*Kidney/an [Analysis];*Liver/an [Analysis];0 (Carrier Proteins);0 (copper-binding protein)","Sato, M.;Arima, M.",1986,Oct,,0,0,
760,[Effect of sera from patients with hepatolenticular degeneration treated with D-penicillamine on the development of Wilsonian gliopathy in vitro],,Adolescent;Adult;Animals;*Astrocytes/pa [Pathology];*Cerebellum/pa [Pathology];Female;*Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Hypertrophy;In Vitro Techniques;Male;Penicillamine/tu [Therapeutic Use];Rats;GNN1DV99GX (Penicillamine),"Weinrauder, H.;Mossakowski, M. J.;Ganuszkina, I. V.",1986,,,0,0,
761,"Plasma and erythrocyte copper, zinc, manganese and magnesium concentrations in Wilson's disease","Plasma copper was significantly reduced in Wilson's disease with decreased ceruloplasmin levels, while there was no significant difference in erythrocyte copper levels between Wilson's disease and controls. Mean zinc and manganese levels in plasma were increased in Wilson's disease, but these differences were not significant. Mean magnesium level in plasma was normal. The levels of these metals in erythrocytes showed no difference between Wilson's disease and controls. Our results suggest that the abnormal copper level in plasma is not due to the primary metabolic defects, but is probanly due to the level of the binding proteins in plasma to this metal, ceruloplasmin, in Wilson's disease.",Adolescent;Adult;*Copper/bl [Blood];*Erythrocytes/me [Metabolism];*Hepatolenticular Degeneration/bl [Blood];Humans;*Magnesium/bl [Blood];*Manganese/bl [Blood];Middle Aged;Osmolar Concentration;Reference Values;*Zinc/bl [Blood];42Z2K6ZL8P (Manganese);789U1901C5 (Copper);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc),"Goto, I.;Kawano, Y.;Tsuchiya, T.;Tamagawa, Y.;Kuroiwa, Y.",1986,,,0,0,
762,Oral zinc therapy normalizes serum uric acid level in Wilson's disease patients,"The authors investigated changes in the serum uric acid (s-UrA) level seen in a Wilson's disease patient who had to undergo oral zinc therapy because of the occurrence of D-penicillamine-induced acute sensitivity reactions, including neutrophilic agranulocytosis, thrombocytopenia, and skin eruptions. Although s-UrA levels were low before oral zinc therapy (mean +/- SD, 1.60 +/- 0.20), they increased (mean +/- SD, 2.63 +/- 0.32) to within normal range (2.8-8.0 mg/dl) after therapy. There were no significant changes in the renal tubular reabsorption of UrA during oral zinc therapy. This therapy also produced an improvement of the decreased cholinesterase (ChE) values usually seen in Wilson's disease. These results suggest that oral zinc therapy can normalize UrA metabolism in Wilson's disease by improving liver dysfunction and increasing UrA synthesis.","Administration, Oral;Child;*Drug Hypersensitivity/dt [Drug Therapy];Drug Hypersensitivity/et [Etiology];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver/me [Metabolism];Liver/pp [Physiopathology];*Penicillamine/ae [Adverse Effects];Uric Acid/bi [Biosynthesis];*Uric Acid/bl [Blood];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];268B43MJ25 (Uric Acid);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Umeki, S.;Ohga, R.;Konishi, Y.;Yasuda, T.;Morimoto, K.;Terao, A.",1986,Nov,,0,0,
763,Wilsons disease in childhood. Surviving severe haemolytic crisis with coma,,Bilirubin/bl [Blood];Coma/pp [Physiopathology];Copper/ur [Urine];Hemolysis;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Penicillamine/ad [Administration & Dosage];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin),"Aagenaes, O.;Berg, K.",1986,,,0,0,
764,Wilson's disease in childhood. A plea for increased awareness,"Wilson's disease, a hepatic-based metabolic disease, is treatable with a relatively good prognosis if diagnosed before severe complications occur. It has been diagnosed in eight children (five boys, three girls) in 11 years at our institution. The presenting symptoms were hepatic in four children, neurological in one and non-specific in one, whereas two children were asymptomatic siblings of index patients. The mean age at diagnosis was 8.9 years (range, 4.7-11.7 years). Two boys died soon after diagnosis: one had fulminating hepatic failure and the other, who had neurological disease, died of aspiration pneumonia. Six children are well, with regression of clinical disease, two to 10 years after the initiation of chelation therapy by mouth. The diagnosis was delayed for all symptomatic patients because of the disease's rarity, its nonspecific early manifestations and a low index of suspicion for the disease on the part of physicians.","Child;Diagnosis, Differential;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/pa [Pathology];Male;Penicillamine/tu [Therapeutic Use];Prognosis;GNN1DV99GX (Penicillamine)","Dorney, S. F.;Kamath, K. R.;Procopis, P. G.;Kan, A. E.",1986,Nov 17,,0,0,
765,Penicillamine-induced elastosis perforans serpiginosa. Tip of the iceberg?,"Elastosis perforans serpiginosa (EPS) is now a well-recognized potential complication of long-term penicillamine therapy. By itself, EPS appears to be a relatively innocuous cutaneous side effect of penicillamine. However, suspicion has been raised in recent literature that EPS may represent only a superficial manifestation of more serious penicillamine-induced systemic elastic tissue damage, particularly involving blood vessels. This is a report of a patient with Wilson's disease who was treated with penicillamine for 14 years. She developed EPS, and histologic examination of the skin revealed the characteristic penicillamine-induced ""lumpy-bumpy"" elastic fibers in the dermis. More important, nonlesional skin showed the same elastic fiber changes. Of greatest significance was the finding of identical elastic fiber alterations in an artery.",Adult;Elastic Tissue/pa [Pathology];Elastic Tissue/ul [Ultrastructure];Female;Humans;*Penicillamine/ae [Adverse Effects];*Skin Diseases/ci [Chemically Induced];Skin Diseases/pa [Pathology];GNN1DV99GX (Penicillamine),"Price, R. G.;Prentice, R. S.",1986,Aug,,0,0,
766,Wilson's disease revisited in the tropics,"The clinical features and investigations of 17 patients were analysed. Thirteen of them were Chinese and the rest Indians. Their ages at presentation ranged from 8 to 63 years (mean 18.35 years). Thirteen patients (76%) were symptomatic; 8 with predominantly hepatic manifestations and 5 with neurological features. Four were asymptomatic siblings. At diagnosis, however, 10(59%) had features of liver involvement singly, 3 (18%) had neurological involvement alone and 4 (27%) had mixed presentations. Family histories were available in 15 patients; 26.9% of siblings had Wilson's Disease. Serum ceruloplasmin was low in 82% of the patients. 24-hour urinary copper was measured in 16 patients and was raised in all of them. About half the patients (41%) had evidence of concomittant renal tubular dysfunction with hypouricaemia and aminoaciduria. Three patients (18%) had joint involvement at presentation. All 17 patients were treated with Penicillamine. Complications due to therapy included pemphigus in one and toxic epidermal necrolysis and later a lupus like syndrome in another. The features of clinical improvement included fading of K-F rings, improvement of neurological signs and the normalisation of serum transaminases. One patient developed primary hepatocellular carcinoma 5 years after presentation. Delay in diagnosis was encountered in half of the patients reviewed. Being a treatable condition, Wilson's Disease, although rare, should always be thought of in patients with haemolysis, liver diseases or extrapyramidal disorders.",Adolescent;Adult;Central Nervous System Diseases/co [Complications];Ceruloplasmin/an [Analysis];Child;Copper/me [Metabolism];Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration;Humans;Liver Diseases/co [Complications];Liver Diseases/pa [Pathology];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Guan, R.;Yeo, P. P.;Ng, H. S.;Chan, H. L.;Gwee, H. M.;Tan, B. Y.;Seah, C. S.;Wong, P. K.;Cheah, J. S.",1986,Apr,,0,0,
767,Penicillamine-induced rapidly progressive glomerulonephritis in patients with progressive systemic sclerosis: successful treatment of two patients and a review of the literature,"Although D-penicillamine has been used effectively in the management of a variety of diseases such as cystinuria, Wilson's disease, rheumatoid arthritis, and progressive systemic sclerosis, several toxic drug reactions have been observed with prolonged administration of this agent. One of the most serious side effects is the renal changes that occur following several months of use. We now report two patients with scleroderma who developed serologic evidence of lupus and crescentic glomerulonephritis during treatment with D-penicillamine. Both patients responded to pulse methylprednisolone and subsequent daily steroids. We also review the current information available on the variety of penicillamine nephropathies.","Adolescent;Adult;Biopsy;Female;*Glomerulonephritis/ci [Chemically Induced];Glomerulonephritis/dt [Drug Therapy];Glomerulonephritis/pa [Pathology];Humans;Kidney Glomerulus/pa [Pathology];Lupus Erythematosus, Systemic/ci [Chemically Induced];Methylprednisolone/tu [Therapeutic Use];*Penicillamine/ae [Adverse Effects];*Scleroderma, Systemic/dt [Drug Therapy];GNN1DV99GX (Penicillamine);X4W7ZR7023 (Methylprednisolone)","Ntoso, K. A.;Tomaszewski, J. E.;Jimenez, S. A.;Neilson, E. G.",1986,Sep,,0,0,
768,Teratogen update: penicillamine,,"*Abnormalities, Drug-Induced;Animals;Collagen/me [Metabolism];Copper/df [Deficiency];*Cutis Laxa/ci [Chemically Induced];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Penicillamine/to [Toxicity];Pregnancy;Pregnancy Complications/dt [Drug Therapy];Skin/me [Metabolism];789U1901C5 (Copper);9007-34-5 (Collagen);GNN1DV99GX (Penicillamine)","Rosa, F. W.",1986,Feb,https://dx.doi.org/10.1002/tera.1420330116,0,0,
769,Trientine for Wilson's disease,,*Ethylenediamines/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Trientine/ae [Adverse Effects];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),Anonymous,1986,Jul 04,,0,0,
770,Orphan drugs,,Caprylates;Carnitine/df [Deficiency];Carnitine/tu [Therapeutic Use];Chelating Agents/tu [Therapeutic Use];Cholelithiasis/dt [Drug Therapy];*Drug Industry;Glycerides/ad [Administration & Dosage];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Orphan Drug Production;Trientine/tu [Therapeutic Use];United States;United States Food and Drug Administration;0 (Caprylates);0 (Chelating Agents);0 (Glycerides);S7UI8SM58A (Carnitine);SJ76Y07H5F (Trientine);VFU0OU98LO (monooctanoin),"Nightingale, S. L.",1986,Jun,,0,0,
771,Pregnancy and penicillamine treatment in a patient with Wilson's disease,"A 22-year-old female with Wilson's disease became pregnant and subsequently delivered a normal infant. At the age of 17 the patient presented evidence of liver cirrhosis and was diagnosed as having Wilson's disease. A regimen of d-penicillamine was started at this time and continued, although irregularly for the 10 months prior to her 9th week of pregnancy. At the 14th week of pregnancy she was started on 500 mg of D-penicillamine a day. She was stable during the remainder of her pregnancy and after delivery. Fetal development was normal and a normal infant was delivered at 35 weeks. It is suggested that pregnancy is not contraindicated in well treated Wilson's disease, and that a regimen of D-penicillamine during pregnancy can control the illness without harming the fetus.","Adult;Ceruloplasmin/me [Metabolism];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Pregnancy;Pregnancy Complications/bl [Blood];*Pregnancy Complications/dt [Drug Therapy];EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Morimoto, I.;Ninomiya, H.;Komatsu, K.;Satho, M.",1986,Feb,,0,0,
772,The management of pregnancy in Wilson's disease treated with trientine,"Seven patients with Wilson's disease, treated with trientine, have been followed during 11 pregnancies. Eight of these resulted in the delivery of normal infants, whilst one was very premature (31 weeks) and was later shown to have a chromosomal defect, isochromosome X. There was one therapeutic termination and one miscarriage associated with a contraceptive coil. The eight children are progressing satisfactorily and have been studied for periods varying from three months to nine years; all mothers are also doing well. The child with the isochromosome X is developing slowly; she shows no morphological abnormalities at this stage. The normal-for-age caeruloplasmin values found in the cord blood indicates that there was no significant copper depletion in the foetuses, as a result of treatment.",Adult;Ceruloplasmin/an [Analysis];Copper/bl [Blood];Copper/ur [Urine];*Ethylenediamines/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Pregnancy;Pregnancy Complications/bl [Blood];*Pregnancy Complications/dt [Drug Therapy];Pregnancy Complications/ur [Urine];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);SJ76Y07H5F (Trientine),"Walshe, J. M.",1986,Jan,,0,0,
773,Thiomolybdates: mediators of molybdenum toxicity and enzyme inhibitors,"The evidence for a role for thiomolybdates in the important ruminant disease syndromes of molybdenosis and Mo-induced hypocuprosis is outlined and present knowledge of their chemistry and metabolism in vivo is reviewed in an attempt to provide a less empirical basis for their toxicology. The compounds are novel enzyme inhibitors in vitro and have also been used therapeutically, apparently successfully, in the treatment of Wilson's disease. While the changes which occur in vivo are complex they can be best understood in terms of an alteration in the affinities for copper of some of the competing ligands, including albumin, which leads to a change in the distribution of copper between the different systemic pools and an overall depletion. [References: 55]",Animals;Copper/me [Metabolism];*Enzyme Inhibitors;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/me [Metabolism];Molybdenum/ae [Adverse Effects];*Molybdenum/me [Metabolism];*Molybdenum/pd [Pharmacology];0 (Enzyme Inhibitors);789U1901C5 (Copper);81AH48963U (Molybdenum);91U3TGV99T (tetrathiomolybdate),"Mason, J.",1986,Dec 15,,0,0,
774,Synergistic neurotoxicity of carbon tetrachloride/carbon disulfide (80/20 fumigants) and other pesticides in grain storage workers,"Neurophysiologic, neurobehavioral, and neuropsychologic profiles in 17 grain storage workers, 1 grain inspector, and 4 malting laboratory workers are described. The effects of CS2 toxicity as seen in viscose rayon workers as well as in experimental animals is remarkably similar to the clinical profile of our grain storage workers. CS2 use explains the dysfunction of peripheral axons, auditory nerve, the optic nerve, and the extrapyramidal system, as well as altered behavior and cognition changes. The signs and symptoms in these workers seem to be dose-related and we note that workers separated out from the areas where fumigation took place reported improvement not seen by fellow workers who continued the fumigant treatment routine. Likewise, malting laboratory workers exposed only to the grain dust from 3 to 7 years showed only minimal symptoms. Though a number of mechanism have been suggested for the alteration of neuropsychological function, the chelating ability of DDC derived from CS2 and its ability to markedly increase copper and zinc within the central nervous system suggests a mechanism of toxicity analogous to copper intoxication as in Wilson's Disease and may explain the production of extrapyramidal symptoms in these patients. Chelation of copper might prove therapeutic in CS2 poisoning. It is obvious that both basic and clinical research will be necessary to sort out the questions raised. We applaud the EPA's decision to ban the use of 80/20 fumigants and also methyl bromide, and trust that similar toxic substances be carefully studied before their selection for replacing these previous toxic agents. We further decry the technique of re-introducing grain dust into the food chain rather than destroying it, since the dust contains very high residues of fumigant material. We speculate on the possible role of CS2 and other pesticides in the food chain and the incidence of Parkinsonian symptoms in these patients and the general public.","Adult;Behavior;*Carbon Disulfide/to [Toxicity];*Carbon Tetrachloride/to [Toxicity];Drug Synergism;Edible Grain;Ethylene Dibromide/to [Toxicity];Hearing Disorders/et [Etiology];Humans;Hydrocarbons, Brominated/to [Toxicity];Movement Disorders/ci [Chemically Induced];*Nervous System Diseases/ci [Chemically Induced];*Occupational Diseases/ci [Chemically Induced];*Pesticides/ae [Adverse Effects];0 (Hydrocarbons, Brominated);0 (Pesticides);1N41638RNO (Ethylene Dibromide);9V42E1Z7B6 (methyl bromide);CL2T97X0V0 (Carbon Tetrachloride);S54S8B99E8 (Carbon Disulfide)","Peters, H. A.;Levine, R. L.;Matthews, C. G.;Sauter, S.;Chapman, L.",1986,,,0,0,
775,"Of mice and men, metals and mutations","Several mutations affecting the transport of copper and zinc in humans and in mice have been discovered over the last 15 years, joining the long known disturbance of copper transport in Wilson's disease. Menkes' disease (classical and mild variant forms) and X linked Ehlers-Danlos syndrome (type IX, X linked cutis laxa) have features in common with one another and with the brindled (Mobr) and blotchy (Moblo) mouse mutants, respectively. There may be one allelic series of mutants in each species or two loci may be involved in each. The toxic milk mutant (tx) in the mouse may be homologous to Wilson's disease in man. The defect of intestinal absorption of zinc in acrodermatitis enteropathica has no homologue yet in the mouse. However, the lethal milk (lm) mutant in the mouse may be homologous to a condition of zinc deficiency described in a few breastfed, low birth weight infants. Many more genetic defects of transport of copper and of zinc may await discovery. Conversely, these mutants are valuable in elucidating the normal processes of copper and zinc transport. [References: 61]","Acrodermatitis/ge [Genetics];Acrodermatitis/me [Metabolism];Alleles;Animals;Biological Transport, Active;*Copper/me [Metabolism];Genetic Linkage;Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Menkes Kinky Hair Syndrome/ge [Genetics];Menkes Kinky Hair Syndrome/me [Metabolism];Mice;Mice, Mutant Strains;*Mutation;Tissue Distribution;Trace Elements/me [Metabolism];X Chromosome;*Zinc/me [Metabolism];0 (Trace Elements);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Danks, D. M.",1986,Apr,,0,0,
776,Genetic diseases of copper metabolism,"There are several known examples of mutations which influence copper homeostasis in humans and animals. Pleiotropic effects are observed when the mutant gene disturbs copper flux. In some cases, the mutation alters the level of a specific copper ligand (enzyme) and the clinical consequences are unique. The two most widely studied genetic maladies in humans are Menkes' and Wilson's diseases. Menkes' disease is an X-linked fatal disorder in which copper accumulates in some organs (intestine and kidney) and is low in others (liver and brain). Wilson's disease is an autosomal recessive disorder in which copper accumulates, if untreated, in liver and subsequently in brain and kidney. Pathophysiological consequences of copper deficiency and toxicity characterize these two disorders. Specific mutations of human cuproenzymes include overproduction of copper-zinc superoxide dismutase in Down's syndrome, absence of tyrosinase in albinism, hereditary mitochondrial myopathy due to reduction in cytochrome c oxidase, and altered lysyl oxidase in X-linked forms of cutis laxa and Ehlers-Danlos syndrome. Mutations altering copper metabolism are also known in animals. Several murine mutants have been studied. The most extensively investigated mutants are the mottled mice, in particular brindled mice, which have a mutation analogous to that of Menkes' disease. Another recently described murine mutation is toxic milk (tx) an autosomal recessive disorder that is characterized by copper accumulation in liver. Two other mutants, crinkled and quaking, were once thought to exhibit abnormal copper metabolism. Recent data has not confirmed this. A mutation in Bedlington terriers has been described which is very similar to Wilson's disease.(ABSTRACT TRUNCATED AT 250 WORDS) [References: 31]","Animals;*Copper/me [Metabolism];Dogs/ge [Genetics];Dogs/me [Metabolism];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Menkes Kinky Hair Syndrome/ge [Genetics];Menkes Kinky Hair Syndrome/me [Metabolism];*Metal Metabolism, Inborn Errors/ge [Genetics];Metal Metabolism, Inborn Errors/me [Metabolism];Mice;Mice, Mutant Strains/ge [Genetics];Mice, Mutant Strains/me [Metabolism];Mutation;789U1901C5 (Copper)","Prohaska, J. R.",1986,,,0,0,
777,Trace elements in development and disease,,"Acrodermatitis/pp [Physiopathology];Cadmium/to [Toxicity];Chromium/me [Metabolism];Copper/df [Deficiency];Copper/me [Metabolism];*Disease;Disease Models, Animal;*Growth;Hemochromatosis;Hepatolenticular Degeneration/pp [Physiopathology];Humans;Iron/me [Metabolism];Magnesium/me [Metabolism];Male;Menkes Kinky Hair Syndrome/pp [Physiopathology];Metallothionein/ph [Physiology];Milk, Human/ph [Physiology];Nucleic Acids/ph [Physiology];Selenium/ph [Physiology];Testis/ph [Physiology];*Trace Elements;Zinc/df [Deficiency];Zinc/ph [Physiology];0 (Nucleic Acids);0 (Trace Elements);00BH33GNGH (Cadmium);0R0008Q3JB (Chromium);789U1901C5 (Copper);9038-94-2 (Metallothionein);E1UOL152H7 (Iron);H6241UJ22B (Selenium);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc)","Garnica, A. D.;Chan, W. Y.;Rennert, O. M.",1986,Feb,,0,0,
778,Compliance in Wilson's disease and in copper toxicosis of Bedlington terriers,,"Animals;Copper/to [Toxicity];Disease Models, Animal;Dogs;Hepatolenticular Degeneration/ci [Chemically Induced];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Patient Compliance;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Sulfates/ae [Adverse Effects];Sulfates/tu [Therapeutic Use];*Zinc/ae [Adverse Effects];Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)","Hoogenraad, T. U.;Rothuizen, J.",1986,Jul 19,,0,0,
779,Dangers of non-compliance in Wilson's disease,"A patient who presented with severe hepatic Wilson's disease at age 14 responded well to treatment with penicillamine and remained in good health for a further 20 years, although she became somewhat careless about her medication towards the end of this period. Finally she abandoned treatment altogether and died of hepatic failure 2 1/2 years later. Abdominal computed tomography showed that the main structural damage to the liver occurred in this relatively short period of non-compliance after over 20 years of normal health on maintenance penicillamine therapy.","Acute Disease;Adolescent;Ascites/dg [Diagnostic Imaging];Ascites/et [Etiology];Brain Chemistry;Copper/an [Analysis];Female;Follow-Up Studies;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/an [Analysis];Liver/dg [Diagnostic Imaging];Liver Cirrhosis/et [Etiology];Long-Term Care;*Patient Compliance;Penicillamine/tu [Therapeutic Use];Recurrence;Tomography, X-Ray Computed;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Walshe, J. M.;Dixon, A. K.",1986,Apr 12,,0,0,
780,Neuropsychiatric aspects of trace elements,Our knowledge of trace element metabolism has increased dramatically in the last decade. It now seems likely that many trace elements are of significance either as causative or therapeutic factors in a wide range of illnesses. Several of the most topical elements are discussed here in relation to neurological and psychiatric disorders.,Alzheimer Disease/ci [Chemically Induced];Copper/ae [Adverse Effects];Hepatolenticular Degeneration/ci [Chemically Induced];Humans;Lead Poisoning/et [Etiology];Magnesium Deficiency/co [Complications];Manganese/ae [Adverse Effects];Neurocognitive Disorders/dt [Drug Therapy];Rubidium/tu [Therapeutic Use];*Substance-Related Disorders/et [Etiology];*Trace Elements/ae [Adverse Effects];Trace Elements/tu [Therapeutic Use];Vanadium/ae [Adverse Effects];Zinc/df [Deficiency];0 (Trace Elements);00J9J9XKDE (Vanadium);42Z2K6ZL8P (Manganese);789U1901C5 (Copper);J41CSQ7QDS (Zinc);MLT4718TJW (Rubidium),"Linter, C. M.",1985,Dec,,0,0,
781,[Wilson's hepatolenticular degeneration. Apropos of a case report],,Adult;Ceruloplasmin/an [Analysis];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Segal, A.;Ducasse, A.;Segal, A.",1985,Jan,,0,0,
782,D-penicillamine and neutrophilic agranulocytosis,,*Agranulocytosis/ci [Chemically Induced];Child;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Neutropenia/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Umeki, S.;Konishi, Y.;Yasuda, T.;Morimoto, K.;Terao, A.",1985,Dec,,0,0,
783,Zinc as a treatment for Wilson's disease--an orphan among orphans,,Copper/bl [Blood];Diet;*Drug Industry;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Orphan Drug Production;Time Factors;Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Brewer, G. J.;Hill, G. M.",1985,,,0,0,
784,Penicillamine therapy for schizophreniform psychosis in Wilson's disease,"A hospitalized 22-year-old woman had suffered from Wilson's disease for the past 11 years. The diagnosis was confirmed by hepatic nonspecific changes, high copper urine excretion, and low to zero serum ceruloplasmin, but psychiatric symptomatology was the main manifestation of the disease. The history of treatment modalities and a controlled trial with penicillamine revealed a clear priority of this drug over phenothiazines in abolishing the psychotic features of the disease. The effective dose in this case was found to be over 1650 mg/day. The mental state, as measured by the Brief Psychiatric Rating Scale, was clearly correlated to the dose of penicillamine. In addition, there was a tendency to increased copper excretion with penicillamine treatment. This case suggests a connection between copper brain poisoning and the related acute psychotic features, which responded well to penicillamine treatment.","Adult;Copper/po [Poisoning];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/co [Complications];Humans;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Psychiatric Status Rating Scales;*Psychoses, Substance-Induced/dt [Drug Therapy];Psychoses, Substance-Induced/et [Etiology];Psychoses, Substance-Induced/px [Psychology];*Psychotic Disorders/dt [Drug Therapy];Psychotic Disorders/et [Etiology];Psychotic Disorders/px [Psychology];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Modai, I.;Karp, L.;Liberman, U. A.;Munitz, H.",1985,Nov,,0,0,
785,Successful pregnancy in Wilson's disease: a case report and review of the literature,"Pregnancy in patients with Wilson's disease can be successfully managed. A case of successful pregnancy in a patient with Wilson's disease is presented. The pathophysiology, protean clinical manifestations and treatment modalities are described.",Adult;Ceruloplasmin/bl [Blood];Copper/ad [Administration & Dosage];Copper/bl [Blood];Copper/tu [Therapeutic Use];Copper/ur [Urine];Diet;Female;Hepatolenticular Degeneration/dh [Diet Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Biller, J.;Swiontoniowski, M.;Brazis, P. W.",1985,,,0,0,
786,[Maintenance treatment of Wilson's disease with oral zinc. Apropos of a child treated for 4 years],"A 13 year-old boy with Wilson's disease was treated with zinc sulphate per os for 4 years. This treatment, which was effective and non toxic, could substitute for penicillamine as long term treatment of Wilson's disease.","Administration, Oral;Adolescent;Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Time Factors;Zinc/pd [Pharmacology];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Alexiou, D.;Hatzis, T.;Koutselinis, A.",1985,Jun-Jul,,0,0,
787,Pseudoxanthoma elasticum-like skin changes induced by penicillamine,,Adolescent;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];*Pseudoxanthoma Elasticum/ci [Chemically Induced];GNN1DV99GX (Penicillamine),"Bentley-Phillips, B.",1985,Sep,,0,0,
788,Peritoneal dialysis with D-penicillamine in Wilson disease,,Albumins/ad [Administration & Dosage];Child;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/th [Therapy];Humans;*Penicillamine/ad [Administration & Dosage];*Peritoneal Dialysis;Solutions;0 (Albumins);0 (Solutions);GNN1DV99GX (Penicillamine),"De Bont, B.;Moulin, D.;Stein, F.;Van Hoof, F.;Lauwerys, R.",1985,Oct,,0,0,
789,Neuropsychological and electrophysiological examination of a patient with Wilson's disease,"A patient with Wilson's disease underwent neuropsychological and electrophysiological examination 4 months following symptom onset. Although motor deficits were more severe, there was considerable impairment of cognitive and intellectual function. Auditory evoked responses were also abnormal in this patient. This case is unusual because of the early severe cognitive deficits.","Adult;Brain Stem/pp [Physiopathology];Copper/ad [Administration & Dosage];Drug Therapy, Combination;*Electrodiagnosis;Electroencephalography;Evoked Potentials, Auditory;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Male;*Neuropsychological Tests;Penicillamine/ad [Administration & Dosage];Pyridoxine/ad [Administration & Dosage];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine)","Bornstein, R. A.;McLean, D. R.;Ho, K.",1985,May,,0,0,
790,On zinc deficiency,,Adult;Alkaline Phosphatase/me [Metabolism];Copper/me [Metabolism];Diet;Hepatolenticular Degeneration/me [Metabolism];Humans;Zinc/bl [Blood];*Zinc/df [Deficiency];Zinc/me [Metabolism];Zinc Radioisotopes;0 (Zinc Radioisotopes);789U1901C5 (Copper);EC 3-1-3-1 (Alkaline Phosphatase);J41CSQ7QDS (Zinc),"van den Hamer, C. J.;Cornelisse, C.",1985,Mar 15,,0,0,
791,[Visually evoked potentials in Wilson's disease],,"Adolescent;Adult;Evoked Potentials, Visual/de [Drug Effects];*Evoked Potentials, Visual;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];Reaction Time;GNN1DV99GX (Penicillamine)","Hamann, K. U.;Hellner, K. A.;Muller-Jensen, A.;Zschocke, S.",1985,,,0,0,
792,Unusual digestive lesions in a patient with Wilson's disease treated with long-term penicillamine,,"*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Ileal Diseases/ci [Chemically Induced];Male;Middle Aged;*Penicillamine/ae [Adverse Effects];Sarcoma, Kaposi/co [Complications];Skin Diseases/ci [Chemically Induced];GNN1DV99GX (Penicillamine)","Wassef, M.;Galian, A.;Pepin, B.;Haguenau, M.;Vassel, P.;Hautefeuille, P.;Brazy, J.",1985,Jul 04,,0,0,
793,[Copper removal using zinc],,Adolescent;Adult;Biotransformation;*Copper/me [Metabolism];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Iris/pa [Pathology];Male;*Sulfates/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Hoogenraad, T. U.",1985,Mar 23,,0,0,
794,Unithiol in Wilson's disease,,*Dimercaprol/aa [Analogs & Derivatives];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Unithiol/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];0CPP32S55X (Dimercaprol);4076-02-2 (Unithiol);J41CSQ7QDS (Zinc),"Hoogenraad, T. U.;Van Hattum, J.",1985,Apr 20,,0,0,
795,Unithiol in Wilson's disease,,Adolescent;Copper/bl [Blood];Copper/ur [Urine];*Dimercaprol/aa [Analogs & Derivatives];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Male;Penicillamine/ae [Adverse Effects];*Unithiol/tu [Therapeutic Use];0CPP32S55X (Dimercaprol);4076-02-2 (Unithiol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1985,Mar 02,,0,0,
796,Inborn errors of trace element metabolism,"Genetic disorders of trace element transport are now known in humans, mice, dogs and cattle. Those involving copper have been known longest and are best known clinically. Effects due to copper deficiency are seen in Menkes' disease, in X-linked cutis laxa and in the X-linked series of mottled mutants in the mouse. Copper accumulation is also harmful, causing damage initially to the liver and later to the kidneys and brain in Wilson's disease, in some Bedlington terriers and in toxic milk mice. Zinc deficiency is seen in acrodermatitis enteropathica and in premature babies born to women who seem to secrete milk that is zinc-deficient, as is seen in lethal milk mice. Study of animal mutants, especially mutant mice, is helpful in understanding the human diseases and identification of the basic defects in trace element transport in these diseases is improving knowledge relevant to trace element nutrition. [References: 59]","Acrodermatitis/di [Diagnosis];Acrodermatitis/ge [Genetics];Animals;Breast Feeding;Copper/df [Deficiency];Copper/me [Metabolism];Cutis Laxa/di [Diagnosis];Cutis Laxa/ge [Genetics];Cutis Laxa/me [Metabolism];Cutis Laxa/th [Therapy];Disease Models, Animal;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Humans;Infant, Newborn;Infant, Premature, Diseases/di [Diagnosis];Liver/me [Metabolism];Manganese/me [Metabolism];Menkes Kinky Hair Syndrome/di [Diagnosis];Menkes Kinky Hair Syndrome/ge [Genetics];Menkes Kinky Hair Syndrome/me [Metabolism];Menkes Kinky Hair Syndrome/th [Therapy];*Metabolism, Inborn Errors/me [Metabolism];Molybdenum/me [Metabolism];Pregnancy;Prenatal Diagnosis;*Trace Elements/me [Metabolism];Zinc/me [Metabolism];0 (Trace Elements);42Z2K6ZL8P (Manganese);789U1901C5 (Copper);81AH48963U (Molybdenum);J41CSQ7QDS (Zinc)","Danks, D. M.",1985,Aug,,0,0,
797,"Clinical, endocrinological and biochemical effects of zinc deficiency","The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been suggested that this trace element may have a role in the in vivo regulation of prolactin release. Thymopoietin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. It is clear that zinc may have several roles in biochemical and hormonal functions of various endocrine organs. Future research in this area is very much needed. [References: 78]",Adrenal Gland Diseases/me [Metabolism];Animals;Biological Availability;Cell Membrane/me [Metabolism];*Endocrine System Diseases/et [Etiology];Enzymes/me [Metabolism];Ethanol/ae [Adverse Effects];Female;Gastrointestinal Diseases/me [Metabolism];Glucose/me [Metabolism];Gonads/ph [Physiology];Humans;Immunity;Metallothionein/me [Metabolism];Nucleic Acids/me [Metabolism];Nutritional Physiological Phenomena;Pregnancy;Pregnancy Complications/me [Metabolism];Prolactin/me [Metabolism];Thymopoietins/me [Metabolism];Thyroid Diseases/me [Metabolism];Wound Healing;*Zinc/df [Deficiency];0 (Enzymes);0 (Nucleic Acids);0 (Thymopoietins);3K9958V90M (Ethanol);9002-62-4 (Prolactin);9038-94-2 (Metallothionein);IY9XDZ35W2 (Glucose);J41CSQ7QDS (Zinc),"Prasad, A. S.",1985,Aug,,0,0,
798,Clinical manifestations of zinc deficiency,"The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal diseases, following uses of certain drugs such as penicillamine for Wilson's disease and diuretics in some cases, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. In pregnancy and during periods of growth the requirement of zinc is increased. The clinical manifestations in severe cases of zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males; it is fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. Its deficiency adversely affects growth in many animal species and humans. Inasmuch as zinc is needed for protein and DNA synthesis and for cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Whether or not zinc is required for the metabolism of somatomedin needs to be investigated in the future. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level; the hypothalamic-pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in cell division, its deficiency may adversely affect testicular size and thus affect its functions. Zinc is required for the functions of several enzymes and whether or not it has an enzymatic role in steroidogenesis is not known at present. Thymopoeitin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. Zinc deficiency affects T-cell functions and chemotaxis adversely. Disorders of cell-mediated immune functions are commonly observed in patients with zinc deficiency. Zinc is beneficial for wound healing in zinc-deficient subjects. In certain zinc-deficient subjects, abnormal taste and abnormal dark adaptation have been noted to reverse with zinc supplementation. [References: 74]","Acrodermatitis/co [Complications];Alcoholism/co [Complications];Anemia, Sickle Cell/co [Complications];Burns/co [Complications];Deficiency Diseases/di [Diagnosis];Deficiency Diseases/dt [Drug Therapy];Diet;Endocrine System Diseases/et [Etiology];Female;Gastrointestinal Diseases/co [Complications];Gastrointestinal Diseases/et [Etiology];Gonads;Growth Disorders/et [Etiology];Humans;Iatrogenic Disease/co [Complications];Immunologic Deficiency Syndromes/et [Etiology];Kidney Diseases/co [Complications];Liver Diseases/co [Complications];Liver Diseases/et [Etiology];Male;Neoplasms/co [Complications];Nervous System Diseases/et [Etiology];Pregnancy;Sensation;Skin Diseases/co [Complications];Wound Healing;*Zinc/df [Deficiency];Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc)","Prasad, A. S.",1985,,https://dx.doi.org/10.1146/annurev.nu.05.070185.002013,0,0,
799,The copper-controlled diet: current aspects of dietary copper restriction in management of copper metabolism disorders,,"Chelating Agents/tu [Therapeutic Use];Copper/df [Deficiency];*Copper/me [Metabolism];*Diet;*Hepatolenticular Degeneration/dh [Diet Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver Cirrhosis, Biliary/co [Complications];*Liver Cirrhosis, Biliary/me [Metabolism];Penicillamine/tu [Therapeutic Use];Prognosis;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Smithgall, J. M.",1985,May,,0,0,
800,Interactions of trace elements: clinical significance,"We examined interaction of the trace element zinc with copper and lead. In sickle cell anemia, the usual situation is one of mild to moderate zinc deficiency owing to renal loss of zinc. Zinc deficiency seems to produce a mild overburden of copper and an increased ceruloplasmin level, probably by enhancing copper absorption. With zinc therapy, this process is reversed. Pharmacological doses of zinc, when administered in a way to ensure effectiveness (without food) will usually lead to copper deficiency. We have taken advantage of the copper-depleting effect of zinc to design a new therapy for Wilson's disease. Zinc, by inducing intestinal metallothionein, inhibits absorption of copper from food, and inhibits reabsorption of endogenously secreted copper, thereby producing a negative copper balance in Wilson's disease. Once we are certain that zinc blocks accumulation of copper in the liver of Wilson's disease patients, zinc therapy will be available as one approach for treating this fatal disease. The animal literature indicates that zinc protects against lead toxicity when both elements are given orally, no doubt through the intestinal metallothionein mechanism. In preliminary experiments in rats, we have not been able to show that toxicity from lead that arrives into the body through a nonoral route is affected by oral zinc supplements. [References: 22]","Anemia, Sickle Cell/dt [Drug Therapy];Ceruloplasmin/bi [Biosynthesis];Copper/df [Deficiency];Copper/me [Metabolism];Copper/ph [Physiology];Drug Interactions;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lead/me [Metabolism];*Trace Elements/ph [Physiology];Zinc/ae [Adverse Effects];Zinc/me [Metabolism];Zinc/ph [Physiology];Zinc/tu [Therapeutic Use];0 (Trace Elements);2P299V784P (Lead);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);J41CSQ7QDS (Zinc)","Brewer, G. J.;Hill, G. M.;Dick, R. D.;Prasad, A. S.;Cossack, Z. T.",1985,,,0,0,
801,Wilson's disease and copper metabolism--a review,,Brain/me [Metabolism];Brain/pa [Pathology];Ceruloplasmin/me [Metabolism];Child;*Copper/me [Metabolism];Cornea/me [Metabolism];Hepatolenticular Degeneration/et [Etiology];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;India;Kidney/me [Metabolism];Liver/me [Metabolism];Liver/pa [Pathology];Liver Cirrhosis/me [Metabolism];Penicillamine/tu [Therapeutic Use];Protein Binding;Zinc/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Manghani, D. K.;Dastur, D. K.",1985,Apr,,0,0,
802,Zinc treatment of Wilson's disease,,Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Brewer, G. J.;Hill, G. M.;Prasad, A. S.;Rabbani, P.",1984,Jul,,0,0,
803,"Haemolytic activity of copper as influenced by chelating agents, albumine and chromium","The haemolytic activity of CuSO4 (0.3 mM) in vitro was reduced in the presence of albumine (5-20 g/l). The presence of D-penicillamine, triethylene tetramine or dimercaptosuccinic acid (0.3 mM) also reduced the copper-induced haemolysis, whereas 2,3-dimercaptopropane-1-sulphonate increased the cytolysis. N-ethylmaleimide (NEM) in appropriate concentrations (1 mM), as well as chromic chloride (0.3 mM), reduced the copper-induced haemolysis. Higher concentrations of NEM (2 mM) were ineffective. The results may provide helpful suggestions as regarding the clinical treatment of copper poisoning and Wilson's disease. The results may also be helpful for the understanding of the mechanisms of haemolysis associated with copper intoxication in vivo.",Adult;*Chelating Agents/pd [Pharmacology];*Chromium/pd [Pharmacology];*Copper/ae [Adverse Effects];Copper Sulfate;*Erythrocyte Membrane/de [Drug Effects];Erythrocytes/me [Metabolism];Glutathione/bl [Blood];*Hemolysis/de [Drug Effects];Humans;Serum Albumin/pd [Pharmacology];0 (Chelating Agents);0 (Serum Albumin);0R0008Q3JB (Chromium);789U1901C5 (Copper);GAN16C9B8O (Glutathione);LRX7AJ16DT (Copper Sulfate),"Aaseth, J.;Skaug, V.;Alexander, J.",1984,Apr,,0,0,
804,Methods for assaying D-penicillamine in a clinical setting,"Penicillamine disulfides have been analysed by automatic amino acid analysis. Because the free thiol reacts poorly with ninhydrin, other detection methods are preferred, particularly high pressure liquid chromatography using an electrochemical detector or gas chromatography with a flame ionization detector. Pharmacokinetic studies have now been reported using these techniques. With patients on established penicillamine regimes, the concentration of free penicillamine in the plasma has been found to vary between 4 and 20 microM depending on dosage and time of administration. Disulfide concentration is higher than this by a factor of 3 or 4 and an even greater quantity is attached to plasma and tissue proteins.","Arthritis, Rheumatoid/bl [Blood];*Arthritis, Rheumatoid/dt [Drug Therapy];Chromatography, Gas;Chromatography, High Pressure Liquid;Cystinuria/bl [Blood];Cystinuria/dt [Drug Therapy];Dose-Response Relationship, Drug;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/aa [Analogs & Derivatives];*Penicillamine/bl [Blood];Penicillamine/tu [Therapeutic Use];Protein Binding;312-10-7 (penicillamine disulfide);GNN1DV99GX (Penicillamine)","Crawhall, J. C.",1984,,,0,0,
805,Hypoparathyroidism in Wilson's disease,,Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Hypoparathyroidism/co [Complications];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),Anonymous,1984,Mar 15,,0,0,
806,[Myasthenia gravis induced by D-penicillamine in a patient with progressive systemic sclerosis],"The development of autoimmune diseases in some patients treated with D-penicillamine (DPA) suggests that the reported occurrence of a conduction disorder at the neuromuscular junction and the development of a reversible myasthenia gravis in rheumatoid disease, progressive systemic sclerosis or Wilson's disease after the use of DPA are part of a general predisposition for autoimmune disease related to DPA therapy. The case reported is an example. The DPA- induced myasthenia gravis (MG) is similar to the spontaneous MG clinically and electrophysiologically, though ocular signs prevail in the former. Antibodies to acetylcholine receptor have been demonstrated and thymic hyperplasia also has been formed. Regarding the onset of myasthenic manifestations the duration of the treatment with DPA varies from 6 to 10 months. The action of DPA on the neuromuscular junction is different from that occurring in spontaneous MG. The pathogenesis of the DPA induced MG is still obscure. The chemical properties of DPA permit it to react with many proteins and some alteration of proteins may appear, with structural changes in the composition and antigenicity of the collagen fibers. In vitro DPA causes disorder of acetylcholine receptor bridges to alpha, beta, gamma sub-units with reduction of the S-S bridges in the gamma-subunit. This decreases the linkage of high affinity and abolishes its positive cooperative system, reducing the S-S connection in the alpha-unit near the acetylcholine linkage. The interaction between DPA and receptor may induce antigenic alteration in this latter, starting the autoimmune phenomena. The other possibility is the stimulation of prostaglandin E-1 synthesis by DPA may fill the allosteric place of ACh receptor, interfering on the neuromuscular junction.","Adult;*Autoimmune Diseases;Female;Humans;*Myasthenia Gravis/ci [Chemically Induced];Neuromuscular Junction/de [Drug Effects];*Penicillamine/ae [Adverse Effects];Penicillamine/me [Metabolism];Penicillamine/pd [Pharmacology];Prostaglandins E/bi [Biosynthesis];Receptors, Cholinergic/me [Metabolism];*Scleroderma, Systemic/co [Complications];0 (Prostaglandins E);0 (Receptors, Cholinergic);GNN1DV99GX (Penicillamine)","Marchiori, P. E.;Scaff, M.;Cossermelli, W.;De Assis, J. L.",1984,Dec,,0,0,
807,Wilson's disease: a 1984 perspective,,"Adolescent;Adult;Bone and Bones/pa [Pathology];Ceruloplasmin/bl [Blood];Child;Child, Preschool;Copper/me [Metabolism];Diagnosis, Differential;Eye/pa [Pathology];Hepatitis, Chronic/di [Diagnosis];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration;Humans;Joints/pa [Pathology];Kidney/pa [Pathology];Liver Diseases/di [Diagnosis];Middle Aged;Nervous System Diseases/et [Etiology];Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Prognosis;Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine)","Ede, R. J.;Mowat, A. P.",1984,Dec,,0,0,
808,Electron probe X-ray analysis on human hepatocellular lysosomes with copper deposits: copper binding to a thiol-protein in lysosomes,"Livers of eight patients with chronic liver diseases were investigated by energy dispersive x-ray analysis. First, three kinds of preparations (osmium-Epon sections, glutaraldehyde-frozen sections, and unfixed-frozen sections) were compared for element detectability at a subcellular level. The glutaraldehyde-frozen sections were satisfactory as far as copper, sulfur, and phosphorus were concerned. Five patients (one patient with Wilson's disease, one chronic cholestasis, one chronic hepatitis, and two asymptomatic primary biliary cirrhosis) yielded x-ray images of copper and sulfur consistent with hepatocellular lysosomes. Second, the glutaraldehyde-frozen sections were utilized for a study of copper deposits in the patients' livers. There was a significant correlation between copper and sulfur contents in the lysosomes of all patients studied but no correlation in the remainder of the cytoplasm. Zinc was not detected in the lysosomes. Whatever the content of copper in the lysosomes, the ratio of delta copper to phosphorus (weight/weight) to delta sulfur to phosphorus was 0.60. These data indicate that most lysosomal copper binds to a thiol protein, probably metallothionein, in the liver.",Adolescent;Adult;*Carrier Proteins/an [Analysis];*Copper/an [Analysis];Electron Probe Microanalysis;Female;Humans;*Liver/an [Analysis];Liver/ul [Ultrastructure];Liver Diseases/me [Metabolism];Liver Diseases/pa [Pathology];*Lysosomes/an [Analysis];Male;Middle Aged;0 (Carrier Proteins);0 (copper-binding protein);789U1901C5 (Copper),"Hanaichi, T.;Kidokoro, R.;Hayashi, H.;Sakamoto, N.",1984,Nov,,0,0,
809,Treatment of Wilson's disease with zinc sulphate,,Adolescent;Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Sulfates/tu [Therapeutic Use];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);J41CSQ7QDS (Zinc),"Walshe, J. M.",1984,Sep 01,,0,0,
810,Effective treatment of Wilson's disease with oral zinc sulphate: two case reports,"Most patients with Wilson's disease are treated with the potentially toxic cupriuretic agent penicillamine. The toxicity of zinc taken by mouth is low, and long term administration induces a negative copper balance. Two patients with severe neurological symptoms were given zinc sulphate by mouth three times daily in doses of 200 mg, later increased to 300 mg. One patient, a 21 year old man, started to receive zinc sulphate after his condition had deteriorated during treatment with cupriuretic drugs. The other, a 27 year old woman, was treated from the start with zinc sulphate. The conditions of both patients improved appreciably, and they were still receiving treatment with zinc sulphate roughly two years later. Effective depletion of body copper stores was shown by an intravenous radiocopper loading test and liver biopsy. No side effects were found. Wilson's disease may effectively be treated with zinc sulphate alone.","Administration, Oral;Adult;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Male;Sulfates/ad [Administration & Dosage];*Sulfates/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];Zinc Sulfate;0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Hoogenraad, T. U.;Van den Hamer, C. J.;Van Hattum, J.",1984,Aug 04,,0,0,
811,Wilson's disease,,"Adolescent;Adult;Child;Child, Preschool;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Middle Aged;Penicillamine/tu [Therapeutic Use];United Kingdom;GNN1DV99GX (Penicillamine)","Parkes, D.",1984,Apr 21,,0,0,
812,Oral zinc therapy for Wilson's disease,,"Administration, Oral;Adult;Animals;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Penicillamine/tu [Therapeutic Use];Zinc/ad [Administration & Dosage];*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc)",Anonymous,1984,May,,0,0,
813,[Febrile reaction to D-penicillamine],"Two personal observations of febrile reaction to D-penicillamine in patients with rheumatoid arthritis provide the opportunity for recalling the clinical presentation which is fairly uniform. The physiopathological mechanism is still unknown. In Wilson disease, progressive reintroduction of the drug may be successful.","Adult;Arthritis, Rheumatoid/dt [Drug Therapy];Female;*Fever/ci [Chemically Induced];Fever/im [Immunology];Humans;Middle Aged;*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine)","Seror, P.;Blotman, F.;Simon, L.",1984,Mar 08,,0,0,
814,The treatment of sickle cell anemia and Wilson's disease with zinc,,"*Anemia, Sickle Cell/dt [Drug Therapy];Calmodulin/ai [Antagonists & Inhibitors];Calmodulin/ph [Physiology];Copper/me [Metabolism];Erythrocyte Membrane/de [Drug Effects];Erythrocyte Membrane/pa [Pathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Phenothiazines/tu [Therapeutic Use];Zinc/df [Deficiency];*Zinc/tu [Therapeutic Use];0 (Calmodulin);0 (Phenothiazines);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Brewer, G. J.;Hill, G. M.",1983,,,0,0,
815,Some therapeutic observations in Wilson's disease,,"Adult;Brain/dg [Diagnostic Imaging];Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dh [Diet Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Middle Aged;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Shoulson, I.;Goldblatt, D.;Plassche, W.;Wilson, G.",1983,,,0,0,
816,Serial changes of cranial computerized tomographic findings in Wilson disease during D-penicillamine therapy,"Serial changes of cranial CT findings were studied in three siblings with Wilson disease during the course of D-penicillamine therapy. The older two cases with neurological presentation revealed low density areas in the region of the basal ganglia on the CT scans performed before treatment. Mild cortical atrophy and mild enlargement of the lateral and the third ventricles were also observed. The chelating therapy resulted in a considerable improvement of neurological symptoms and disappearance of Kayser-Fleischer rings. The low density areas of the basal ganglia disappeared. However, cortical atrophy and an enlargement of the ventricles were still present. In an asymptomatic girl, the cranial CT scans remained normal after chelating therapy. The cranial CT scan is considered to be of great use both in diagnosis and observation of the clinical course in Wilson disease, and it is also of prognostic value.","Adolescent;*Brain/dg [Diagnostic Imaging];Child;Female;Hepatolenticular Degeneration/dg [Diagnostic Imaging];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;*Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Mizutani, N.;Maehara, M.;Negoro, T.;Watanabe, K.",1983,,,0,0,
817,The effect of chelation therapy on the amino aciduria and peptiduria of Wilson's disease,"1. There is an excess urinary output of free amino acids and of urinary peptides in most cases of untreated Wilson's disease. Studies of 11 patients have shown that both these abnormalities are greatly improved by two years of standard chelation therapy. 2. The reduction in excretion of both free amino acids and peptides is purely quantitative, there being no significant change in the percentage composition of amino acids, either free or combined, in relation to their total urinary output. 3. Arguments are advanced that the peptiduria of the disease is usually due to a proximal renal tubular reabsorption defect, but in rare cases it may be due to excess bone breakdown or even to a combination of bone and renal tubular disease in the same patient.",Adolescent;Adult;*Amino Acids/ur [Urine];*Chelating Agents/tu [Therapeutic Use];Child;*Ethylenediamines/tu [Therapeutic Use];Female;Follow-Up Studies;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ur [Urine];Humans;Male;Oligopeptides/ur [Urine];*Penicillamine/tu [Therapeutic Use];*Peptides/ur [Urine];*Trientine/tu [Therapeutic Use];0 (Amino Acids);0 (Chelating Agents);0 (Ethylenediamines);0 (Oligopeptides);0 (Peptides);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Asatoor, A. M.;Milne, M. D.;Walshe, J. M.",1983,Apr,,0,0,
818,Wilson's disease in one identical twin and treatment by triethylene tetramine 2HCl in another case,,"Adolescent;Adult;*Diseases in Twins;*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Male;Pregnancy;*Trientine/tu [Therapeutic Use];Twins, Monozygotic;0 (Ethylenediamines);SJ76Y07H5F (Trientine)","Watson, R. G.",1983,,,0,0,
819,Hepatolenticular degeneration: histological study of conjunctiva and observation of chalazii during D-penicillamine treatment,"Three patients with hepatolenticular degeneration (Wilson's disease) are described. Bilateral blepharoconjunctivitis and Kayser-Fleischer ring was observed in all 3 patients. In 2 patients, long-lasting, bilateral chalazii appeared during chronic treatment with D-penicillamine. Histochemical and ultrastructural studies of pre-treatment conjunctival biopsies showed no copper storage in the tissue thus supporting the hypothesis that copper storage in Descemet's membrane derives from the anterior chamber.","Adolescent;Adult;Child, Preschool;Conjunctiva/me [Metabolism];*Conjunctiva/pa [Pathology];Copper/me [Metabolism];*Cysts/ci [Chemically Induced];Descemet Membrane/me [Metabolism];*Eyelid Diseases/ci [Chemically Induced];Female;Follow-Up Studies;*Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Meibomian Glands;*Penicillamine/ae [Adverse Effects];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Loffredo, A.;Sammartino, A.;Cecio, A.;Campanella, G.",1983,Oct,,0,0,
820,Penicillamine-induced dermatomyositis. A case history,"A 69-year-old woman with classical rheumatoid arthritis developed a severe dermato-myopathy during treatment with penicillamine. Remission occurred on withdrawal of the drug. Penicillamine (dimethylcysteine) is a pharmacological agent used for its chelating properties in the treatment of Wilson's disease and heavy metal poisoning, and in cysteinuria because of soluble disulphide formation. Within the last 17 years penicillamine has been increasingly applied in the treatment of rheumatoid arthritis, the mechanism of action still being unknown. A great number of side effects have been reported, including less common auto-immune disorders such as drug-induced systemic lupus erythematosus, myasthenia gravis and polymyositis. These and other possible side effects have been well reviewed by others (1, 2). To our knowledge only a few earlier cases of dermatomyositis as a complication to penicillamine treatment of rheumatoid arthritis have been reported (3, 4, 5). We describe here another case.","Aged;Arthritis, Rheumatoid/dt [Drug Therapy];*Dermatomyositis/ci [Chemically Induced];Dermatomyositis/pa [Pathology];Dermatomyositis/pp [Physiopathology];Electromyography;Female;Humans;*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine)","Lund, H. I.;Nielsen, M.",1983,,,0,0,
821,Treatment of Wilson's disease,,Copper/me [Metabolism];Diagnostic Errors;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Penicillamine/tu [Therapeutic Use];Trientine/tu [Therapeutic Use];Zinc/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);SJ76Y07H5F (Trientine),"Deiss, A.",1983,Sep,,0,0,
822,Oral zinc therapy for Wilson's disease,"Wilson's disease is an inherited disorder of copper accumulation that is fatal if untreated. Because penicillamine, the established treatment, is toxic in a substantial number of patients, we studied the efficacy of zinc treatment. We induced a negative or neutral copper balance in five out of five patients with Wilson's disease who were receiving no therapy other than zinc. Zinc acetate was given every 4 hours during the day, and the patient was not allowed to eat for 1 hour before and 1 hour after each dose. Oral zinc therapy, used according to our regimen, may now be considered in the treatment of patients with penicillamine intolerance. However, it is premature to convert patients to zinc therapy if they tolerate penicillamine well. The efficacy of zinc therapy in the initial removal of the copper burden in acutely ill patients with Wilson's disease has not yet been evaluated.","Acetates/ad [Administration & Dosage];Acetic Acid;Administration, Oral;Adult;Copper/me [Metabolism];Copper/ur [Urine];Drug Administration Schedule;Feces/an [Analysis];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];*Zinc/ad [Administration & Dosage];Zinc/me [Metabolism];0 (Acetates);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);Q40Q9N063P (Acetic Acid)","Brewer, G. J.;Hill, G. M.;Prasad, A. S.;Cossack, Z. T.;Rabbani, P.",1983,Sep,,0,0,
823,3 years of continuous oral zinc therapy in 4 patients with Wilson's disease,"A competitive relationship exists between copper and zinc: among other effects, excessive dietary zinc is known to decrease the absorption of copper from the gastro-intestinal tract. The purpose of this study is to investigate the effectiveness of oral zinc therapy in 4 patients with Wilson's disease, who, during a 3-year period, took zinc as their only medication to influence their copper metabolism. Physical examinations, oral 64Cu loading tests, plasma concentrations of copper, zinc and ceruloplasmin, and the urinary copper excretion were used to monitor the effect of therapy. The dosages used ranged from 3 x 100 to 3 x 400 mg zinc sulphate per day. The clinical and biochemical results of the oral zinc therapy were good in all 4 patients and no toxic side-effects were seen. Our conclusion from this study is that oral zinc may well be a low toxic alternative to D-penicillamine in the treatment of Wilson's disease.","Administration, Oral;Adolescent;Adult;Ceruloplasmin/me [Metabolism];Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Middle Aged;Radioisotopes;*Sulfates/ad [Administration & Dosage];*Zinc/ad [Administration & Dosage];Zinc/bl [Blood];Zinc Sulfate;0 (Radioisotopes);0 (Sulfates);7733-02-0 (Zinc Sulfate);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);J41CSQ7QDS (Zinc)","Hoogenraad, T. U.;Van den Hamer, C. J.",1983,Jun,,0,0,
824,Biological roles of ionic zinc,"We tentatively conclude from our work that intracellular calcium acts as a second messenger to affect membrane function through activation of calmodulin. This activation, if too great, leads to pathological erythrocyte adherence and aggregation phenomena. We have shown that calmodulin inhibitors can prevent some of these calcium-induced abnormalities. Since some of this work involves a very specific anticalmodulin antibody, it appears very likely that calmodulin is involved in producing membrane effects. Zinc appears to act upon the membrane in part, at least, through the inhibition of calmodulin action. Our work leads us to believe that zinc regulates copper absorption from the gastrointestinal tract in a somewhat complex manner. That is, direct zinc-copper antagonism within the lumen of the gastrointestinal tract is not adequate to explain the effects of zinc on inhibiting copper absorption in man. It appears from our work that tissues must become loaded with zinc before an effect on copper absorption is observed. This produces a lag effect during which zinc administration does not produce a negative copper balance. However, after this lag effect, zinc has produced a negative to neutral copper balance in 5 of 5 Wilson's disease patients studied. At this time, therefore, we believe that zinc therapy can be offered as an alternative to penicillamine therapy in previously decoppered patients or patients who are not yet symptomatic. However, we recommend that this therapy only be used at this time in accordance with the one zinc therapy regimen we have tested. [References: 35]","Anemia, Sickle Cell/dt [Drug Therapy];Calcium Channel Blockers;Calmodulin/me [Metabolism];Copper/me [Metabolism];Erythrocyte Membrane/de [Drug Effects];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Intestinal Absorption/de [Drug Effects];Sialic Acids/bl [Blood];Zinc/pd [Pharmacology];*Zinc/ph [Physiology];Zinc/tu [Therapeutic Use];0 (Calcium Channel Blockers);0 (Calmodulin);0 (Sialic Acids);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Brewer, G. J.;Hill, G. M.;Prasad, A. S.;Cossack, Z. T.",1983,,,0,0,
825,Physiological ligands for copper and zinc,,"Absorption;Acrodermatitis/et [Etiology];Animals;Biological Availability;Biological Transport, Active;Blood Proteins/me [Metabolism];Copper/me [Metabolism];*Copper/ph [Physiology];Enzymes/me [Metabolism];Hepatolenticular Degeneration/et [Etiology];Humans;Ligands;Menkes Kinky Hair Syndrome/et [Etiology];Metallothionein/me [Metabolism];Zinc/me [Metabolism];*Zinc/ph [Physiology];0 (Blood Proteins);0 (Enzymes);0 (Ligands);789U1901C5 (Copper);9038-94-2 (Metallothionein);J41CSQ7QDS (Zinc)","DiSilvestro, R. A.;Cousins, R. J.",1983,,https://dx.doi.org/10.1146/annurev.nu.03.070183.001401,0,0,
826,Wilson's disease and hepatocellular carcinoma: possible protective role of copper,"A male patient with Wilson's disease developed a hepatocellular carcinoma after treatment for nine years with D-penicillamine. Examination at necropsy showed that excess liver copper had been effectively removed. As copper has been shown to protect against chemically induced hepatocellular carcinoma in rats, this may be the reason for the extreme rarity of hepatocellular carcinoma in patients with Wilson's disease and possibly in other liver diseases with hepatic copper overload.","Adult;*Carcinoma, Hepatocellular/co [Complications];Carcinoma, Hepatocellular/pa [Pathology];*Copper/me [Metabolism];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Liver/pa [Pathology];*Liver Neoplasms/co [Complications];Liver Neoplasms/pa [Pathology];Male;789U1901C5 (Copper)","Wilkinson, M. L.;Portmann, B.;Williams, R.",1983,Aug,,0,0,
827,Penicillamine: review and cutaneous manifestations,"D-Penicillamine, a heavy metal chelator used in the treatment of Wilson's disease and other conditions, may be associated with both noncutaneous and cutaneous side effects. Some of the cutaneous lesions are due to a toxic-metabolic effect on connective tissue; some may be explained on the basis of autoimmunity; some are acute sensitivity reactions, and some are secondary to unknown mechanisms. The types of cutaneous manifestations may, in some instances, be correlated with the disease being treated and the dosage and duration of penicillamine therapy. [References: 136]","*Autoimmune Diseases/ci [Chemically Induced];Collagen/me [Metabolism];Dermatitis, Atopic/ci [Chemically Induced];*Drug Eruptions/et [Etiology];Elastin/me [Metabolism];Humans;Lichen Planus/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/me [Metabolism];Penicillamine/tu [Therapeutic Use];Skin/de [Drug Effects];Stomatitis, Aphthous/ci [Chemically Induced];9007-34-5 (Collagen);9007-58-3 (Elastin);GNN1DV99GX (Penicillamine)","Levy, R. S.;Fisher, M.;Alter, J. N.",1983,Apr,,0,0,
828,Studies in pancreatic secretion: VIII. Pancreatic function in patients with Wilson's disease,,Adolescent;Adult;Amylases/se [Secretion];Child;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;*Pancreas/pp [Physiopathology];Pancreatic Function Tests;Penicillamine/tu [Therapeutic Use];Secretin;1393-25-5 (Secretin);EC 3-2-1 (Amylases);GNN1DV99GX (Penicillamine),"Dreiling, D. A.;Grateron, H.",1983,Jul-Aug,,0,0,
829,The copper hypothesis of schizophrenia: a review,"The hypothesis that excess tissue copper can cause schizophrenia is a relatively old theory that has never been compellingly demonstrated nor convincingly refuted. This article traces the development and abandonment of the copper hypothesis and examines the evidence for and against the etiological involvement of copper in schizophrenia. A plausible mechanism by which copper excesses could result in schizophrenia is presented and evaluated, and various attempts to reconcile the contradictory data are considered.",Ceruloplasmin/me [Metabolism];*Copper/bl [Blood];Copper/po [Poisoning];Dopamine/me [Metabolism];Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/px [Psychology];Humans;Melanins/me [Metabolism];Penicillamine/tu [Therapeutic Use];*Schizophrenia/bl [Blood];Schizophrenia/ci [Chemically Induced];Schizophrenia/dt [Drug Therapy];0 (Melanins);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);VTD58H1Z2X (Dopamine),"Bowman, M. B.;Lewis, M. S.",1982,Fall,,0,0,
830,The cardiomyopathy of Wilson's disease. Myocardial alterations in nine cases,"Though myocardial alterations are well recognized in haemochromatosis, little attention has been paid to the cardiac changes in Wilson's disease. To define the extent of myocardial degeneration in newly diagnosed or chronically treated Wilson's disease, we reviewed the autopsy findings in 9 cases with this condition. We compared our observations with those in 3 control cases, selected for comparable age and with liver disease having no known association with cardiac degeneration. Our results revealed cardiac hypertrophy in 5 out of 9 cases of Wilson's disease. There was evidence of interstitial and replacement fibrosis, intramyocardial small vessel sclerosis and focal inflammatory cell inflammation to a variable degree in all cases. One case had AV nodal degeneration, and a 15 year old boy had severe atherosclerosis of the left main coronary artery. Two patients died suddenly, presumably secondary to an arrhythmia; one of these patients had the most marked myocardial alterations. We could not correlate these changes specifically with the tissue levels of copper, treatment with D-penicillamine, or the presence of cirrhosis. We conclude that there are definite morphological abnormalities in the hearts of patients with Wilson's disease consistent with a cardiomyopathy. Though the myocardial changes were non-specific, the fact that 2 patients died suddenly, suggests the need for a prospective study of cardiac function in these patients in the future.",Adolescent;Adult;Atrioventricular Node/pa [Pathology];Autopsy;Cardiomyopathies/et [Etiology];*Cardiomyopathies/pa [Pathology];Coronary Vessels/pa [Pathology];Electrocardiography;Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Middle Aged;Myocardium/pa [Pathology];Organ Size,"Factor, S. M.;Cho, S.;Sternlieb, I.;Scheinberg, I. H.;Goldfischer, S.",1982,,,0,0,
831,Oral zinc treatment in primary biliary cirrhosis,,"Administration, Oral;Adult;Aged;Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver/me [Metabolism];*Liver Cirrhosis, Biliary/dt [Drug Therapy];Male;Middle Aged;*Zinc/tu [Therapeutic Use];789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Olsson, R.",1982,,,0,0,
832,Effective treatment of Wilson's disease with oral zinc,,"Administration, Oral;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Zinc/tu [Therapeutic Use];J41CSQ7QDS (Zinc)","Hoogenraad, T. U.",1982,Oct,,0,0,
833,Treatment of a presymptomatic 14-year-old girl with Wilson's disease,,Adolescent;Ceruloplasmin;Copper/ur [Urine];Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Holmgren, G.;Samuelson, G.;Sjogren, S.",1982,,,0,0,
834,"Zinc, the brain and behavior","The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.","Animals;*Behavior, Animal/ph [Physiology];*Brain/me [Metabolism];Copper/me [Metabolism];Female;Hippocampus/me [Metabolism];Histamine/me [Metabolism];Hormones/bl [Blood];Humans;Iron/me [Metabolism];Magnesium/me [Metabolism];Neural Conduction;Pregnancy;Retina/me [Metabolism];Schizophrenia/me [Metabolism];Taste/ph [Physiology];Zinc/df [Deficiency];*Zinc/me [Metabolism];0 (Hormones);789U1901C5 (Copper);820484N8I3 (Histamine);E1UOL152H7 (Iron);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc)","Pfeiffer, C. C.;Braverman, E. R.",1982,Apr,,0,0,
835,Acute lymphoblastic leukemia in a patient receiving penicillamine for Wilson's disease,,"Adolescent;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/im [Immunology];Humans;Immunity, Cellular/de [Drug Effects];Immunoglobulin A/an [Analysis];*Leukemia, Lymphoid/ci [Chemically Induced];Leukemia, Lymphoid/im [Immunology];Leukocyte Count;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];Risk;Time Factors;0 (Immunoglobulin A);GNN1DV99GX (Penicillamine)","Gilman, P. A.;Holtzman, N. A.",1982,Jul 23,,0,0,
836,[Wilson's disease. II],,Adolescent;Bone Diseases/et [Etiology];Ceruloplasmin/an [Analysis];Child;Copper/an [Analysis];Eye Diseases/et [Etiology];Female;Hematologic Diseases/et [Etiology];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Heterozygote;Humans;Kidney Diseases/et [Etiology];Liver Diseases/et [Etiology];Male;Nervous System Diseases/et [Etiology];Penicillamine/tu [Therapeutic Use];Prognosis;Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Sanchez Rodriguez, A.;Gonzalez Macias, J.;Diez Jarilla, J. L.;Suquia Mugica, B.;de Portugal Alvarez, J.",1982,Aug,,0,0,
837,Screening asymptomatic family members for Wilson's disease,,Adolescent;Ceruloplasmin/an [Analysis];Copper/an [Analysis];Copper/ur [Urine];Female;*Genetic Testing;*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Heterozygote Detection;Homozygote;Humans;Liver/an [Analysis];Male;Penicillamine;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Lindahl, J. A.;Sharp, H. L.",1982,Aug,,0,0,
838,Disorders of mineral metabolism,,"Acrodermatitis/ge [Genetics];Child, Preschool;Copper/df [Deficiency];Female;Hemochromatosis/ge [Genetics];Hepatolenticular Degeneration/ge [Genetics];Humans;Hypophosphatemia, Familial/ge [Genetics];Infant;Infant, Newborn;Intestinal Absorption;Magnesium Deficiency/ge [Genetics];Male;Menkes Kinky Hair Syndrome/ge [Genetics];Metal Metabolism, Inborn Errors/ge [Genetics];Metal Metabolism, Inborn Errors/pp [Physiopathology];*Metal Metabolism, Inborn Errors;Trace Elements/df [Deficiency];Zinc/df [Deficiency];0 (Trace Elements);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Hambidge, K. M.;Walravens, P. A.",1982,Jan,,0,0,
839,Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis,"Skin rashes, proteinuria, systemic lupus erythematosus, polymyositis and myasthenia gravis have all been recorded as complications of penicillamine therapy in patients with rheumatoid arthritis. A patient who had developed all 5 is now described. The skin lesion resembled elastosis perforans serpiginosa, which has been reported as a rare side effect in patients with Wilson's disease but not in patients with rheumatoid arthritis treated with penicillamine.","Adult;*Arthritis, Rheumatoid/dt [Drug Therapy];Drug Eruptions/et [Etiology];Humans;Lupus Erythematosus, Systemic/ci [Chemically Induced];Male;Myasthenia Gravis/ci [Chemically Induced];Myositis/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Proteinuria/ci [Chemically Induced];GNN1DV99GX (Penicillamine)","Essigman, W. K.",1982,Dec,,0,0,
840,Penicillamine in Wilson's disease,,Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Danks, D. M.",1982,Aug 21,,0,0,
841,Penicillamine in Wilson's disease,,Drug Evaluation;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"May, P. M.;Jones, D. C.;Williams, D. R.",1982,Jul 31,,0,0,
842,Penicillamine in Wilson's disease,,*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ep [Epidemiology];Humans;*Penicillamine/tu [Therapeutic Use];United States;GNN1DV99GX (Penicillamine),"Scheinberg, I. H.",1982,Jun 26,,0,0,
843,"Wilson's disease, an end to the search for new therapy?",,Animals;*Ethylenediamines/tu [Therapeutic Use];Hepatolenticular Degeneration;Humans;Penicillamine/tu [Therapeutic Use];Risk;Trientine/ae [Adverse Effects];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"May, P. M.;Jones, D. C.;Williams, D. R.",1982,May 15,,0,0,
844,Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride,"Twenty patients with Wilson's disease in whom severe penicillamine intolerance developed have been managed with the orally active chelating agent trientine dihydrochloride (trien). The stage of illness of the patients ranged from the presymptomatic through severe neurological or hepatic disease to the ""decoppered"" postsymptomatic cases. Trien has proved to be a safe and highly effective treatment both for reversing symptoms and for maintaining patients previously successfully decoppered with penicillamine. There has been evidence of depletion of the body stores of copper by trien coinciding with the clinical improvement. In most of the patients the toxic symptoms which forced a change of therapy were reversed on trien therapy; however, elastosis perforans did not seem to benefit, and two patients with penicillamine-induced systemic lupus erythematosus were not helped by the change. No other toxic signs or symptoms were observed. There was no evidence of teratogenicity either in animals or in the six patients who became pregnant while taking trien; all six infants have developed normally. Trien is a satisfactory alternative therapy for Wilson's disease; its usefulness, is however, severely limited by the lack of a product license.","Adolescent;Adult;Brain/dg [Diagnostic Imaging];*Ethylenediamines/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/dg [Diagnostic Imaging];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Pregnancy;Tomography, X-Ray Computed;*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Walshe, J. M.",1982,Mar 20,,0,1,
845,Computerized cranial tomography in Wilson disease: report of a case before and after penicillamine therapy,"A patient with Wilson Disease presenting neurologic signs was treated with d-Penicillamine. Computerized cranial tomography (CT) performed before therapy showed symmetrical areas of low density in the region of the basal ganglia, enlargement of ventricles and bilateral increased density of the medial nuclei of the thalamus. This abnormality of the thalamus had not been reported previously in Wilson disease. After two years therapy there was an evident clinical improvement and at the same time a reduction of CT abnormalities. The reports on CT scanning in Wilson disease are reviewed.","Adolescent;Hepatolenticular Degeneration/dg [Diagnostic Imaging];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];Tomography, X-Ray Computed;GNN1DV99GX (Penicillamine)","Lanzi, G.;Balottin, U.;Cecchini, A.;Ottolini, A.",1981,Dec,,0,0,
846,Wilson's disease. An analysis of the cranial computerized tomographic appearances found in 60 patients and the changes in response to treatment with chelating agents,"Sixty patients with Wilson's disease have been studied by means of computerized cranial tomography (CT). The findings are described and analysed with particular reference to their value, both diagnostic and prognostic, in the management of this disease. The commonest abnormalities were ventricular dilation, 73 per cent; cortical atrophy, 63 per cent; brain-stem atrophy, 55 per cent. Characteristic hypodense areas in the regions of the basal ganglia were present in 45 per cent and almost invariably these were accompanied by one or more of the other CT abnormalities. This combination of findings is considered specific for Wilson's disease in the appropriate clinical context. CT abnormalities were most common and most marked in patients with a neurological presentation, only 2 out of 40 having a normal scan. Similar changes were also demonstrated in three-quarters of the patients with an hepatic presentation and nearly half of those who were presymptomatic. Nineteen patients were scanned on more than one occasion to assess the influence of treatment with penicillamine or triethylene tetramine on the abnormalities recorded initially. Fourteen showed basal ganglia hypodensities on first scanning and in ten of these there was a moderate to marked improvement in this abnormality in response to therapy. Corresponding with this there was considerable clinical improvement. Despite the findings of quite severe CT abnormalities in patients with Wilson's disease. suggesting considerable loss of neurons, patients will still respond well to treatment. We conclude that although the CT. Examination of patients with Wilson's disease is of value both in diagnosis and management, it is of no great help in prognosis.","Adolescent;Adult;Atrophy;Brain/pa [Pathology];Cerebral Ventricles/pa [Pathology];Child;Dilatation, Pathologic;*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Motor Skills/de [Drug Effects];*Penicillamine/tu [Therapeutic Use];*Tomography, X-Ray Computed;*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine)","Williams, F. J.;Walshe, J. M.",1981,Dec,,0,0,
847,D-penicillamine and the ocular myasthenic syndrome,"D-penicillamine is a potent drug used to treat rheumatoid arthritis, Wilson's disease and cystinuria. D-penicillamine has recently been found to cause myasthenia gravis in certain susceptible patients. We present a typical case of one patient who developed myasthenia while taking D-penicillamine. The withdrawal of D-penicillamine and the institution of short-term anticholinesterase therapy resulted in the resolution of this disease. The literature is reviewed and attention is focused on the point that all patients who developed myasthenia while undergoing D-penicillamine therapy had ocular symptoms.","Arthritis, Rheumatoid/dt [Drug Therapy];*Blepharoptosis/ci [Chemically Induced];*Diplopia/ci [Chemically Induced];Female;Humans;Middle Aged;*Myasthenia Gravis/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Kimbrough, R. L.;Mewis, L.;Stewart, R. H.",1981,Oct,,0,0,
848,Is copper hepatotoxic in primary biliary cirrhosis?,"In primary biliary cirrhosis (PBC) liver copper retention occurs as a complication of cholestasis. By analogy with Wilson's disease, it has been suggested that copper retention is hepatotoxic in PBC, and this has been the rationale for the use of D-penicillamine in this disease. The hypothesis that copper is hepatotoxic in PBC has not been tested and in this study we have evaluated the role of liver copper retention in the pathogenesis of PBC. Sixty-four patients with PBC have been studied. Fifty-four had increased liver copper concentrations. Liver cell synthetic function was well preserved. All the patients had normal prothrombin times, and only two had subnormal serum albumin concentrations. There was no correlation between liver copper concentrations and the degree of liver cell damage assessed biochemically (aspartate transaminase), and histologically. Electron microscopy was performed on liver biopsies from five patients with markedly increased liver copper concentrations. The liver cell ultrastructure was compatible with cholestasis. Liver cells contained electron dense lysosomes, which were shown to contain copper and sulphur by x-ray probe microanalysis. The characteristic organelle changes associated with copper toxicity in Wilson's disease were not observed. The biochemical, histological, and histochemical differences between PBC complicated by liver copper retention, and Wilson's disease, indicates that there are differences in the handling of copper in these disease. In this study we could find no evidence to suggest that copper plays an important role in the pathogenesis of liver dysfunction in PBC.","*Copper/an [Analysis];Humans;*Liver/an [Analysis];Liver/ul [Ultrastructure];*Liver Cirrhosis, Biliary/me [Metabolism];Liver Cirrhosis, Biliary/pa [Pathology];Microscopy, Electron;789U1901C5 (Copper)","Epstein, O.;Arborgh, B.;Sagiv, M.;Wroblewski, R.;Scheuer, P. J.;Sherlock, S.",1981,Oct,,0,0,
849,[Copper metabolism: ultimate therapeutic implications in cholestasis],,*Cholestasis/dt [Drug Therapy];Cholestasis/me [Metabolism];Cholestasis/pp [Physiopathology];*Copper/me [Metabolism];Copper/tu [Therapeutic Use];Hepatolenticular Degeneration/me [Metabolism];Humans;*Liver/me [Metabolism];Liver Cirrhosis/et [Etiology];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Thierman-Duffaud, D.;Levy, V. G.",1981,,,0,0,
850,[Penicillamine-induced elastosis perforans serpiginosa and pulmonary cyst in Wilson's disease (author's transl)],"A large air cyst was removed from the right lung of a 29-year-old female patient with Wilson's disease and penicillamine-induced perforating elastosis, the cyst first appearing after 9 years of treatment with penicillamine. Since, on the one hand, the microscopic and ultrastructural changes in the elastic tissue of the lungs were identical to those observed in the skin, both in areas of clinically-demonstrable elastosis perforans serpiginosa and clinically unaffected skin and, on the other hand, no other pulmonary disease was demonstrable to account for the development of the cystic lesion, it is concluded that penicillamine is the causative factor by means of extensive alteration of the elastic tissue. The morphological changes in the elastic fibres are so characteristic that it is easy to distinguish penicillamine-induced elastosis perforans serpiginosa from the idiopathic variant.",Adult;*Cysts/ci [Chemically Induced];Cysts/pa [Pathology];*Elastic Tissue/de [Drug Effects];Elastic Tissue/pa [Pathology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Lung/pa [Pathology];*Lung Diseases/ci [Chemically Induced];Lung Diseases/pa [Pathology];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Skin/pa [Pathology];*Skin Diseases/ci [Chemically Induced];Skin Diseases/pa [Pathology];GNN1DV99GX (Penicillamine),"Bardach, H.;Gebhart, W.;Niebauer, G.;Bardach, G.",1981,Feb 20,,0,0,
851,Bilateral serous retinal detachment with thrombocytopenia during penicillamine therapy,,Adult;Female;Fluorescein Angiography;Fundus Oculi;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Macula Lutea;*Penicillamine/ae [Adverse Effects];*Retinal Detachment/et [Etiology];Thrombocytopenia/ci [Chemically Induced];*Thrombocytopenia/co [Complications];GNN1DV99GX (Penicillamine),"Klepach, G. L.;Wray, S. H.",1981,Feb,,0,0,
852,"The ""lumpy-bumpy"" elastic fiber. A marker for long-term administration of penicillamine","A 29-year-old woman with Wilson's disease developed dermolytic skin lesions 2 years after initiation of treatment with penicillamine. Eight years later, still on penicillamine therapy, striae appeared over both of her breasts. Biopsy of involved skin during the 10th year of treatment with penicillamine revealed characteristic lumpy-bumpy alterations of dermal elastic fibers which were not present in the first skin biopsy 8 years previously. Biopsy of a stria showed changes similar to those in the dermolytic skin lesions. Lumpy-bumpy elastic fibers are pathognomonic for penicillamine-induced elastosis. They are easily recognizable with examination by conventional microscopy. Their appearance may serve as a warning of potentially serious, widespread elastic tissue involvement. These abnormal elastic fibers are not only found in the skin, but also in the lungs.",Adult;Elastic Tissue/de [Drug Effects];*Elastic Tissue/pa [Pathology];Elastic Tissue/ul [Ultrastructure];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Lung/pa [Pathology];*Penicillamine/ae [Adverse Effects];*Skin/de [Drug Effects];Skin/pa [Pathology];GNN1DV99GX (Penicillamine),"Gebhart, W.;Bardach, H.",1981,Spring,,0,0,
853,[Main characteristics of the treatment of liver cirrhosis],,"Adolescent;Adult;Ascites/th [Therapy];Bed Rest;Bloodletting;Child;Child, Preschool;Cholestyramine Resin/tu [Therapeutic Use];Dietary Fats;Dietary Proteins/ae [Adverse Effects];Diuretics/tu [Therapeutic Use];Energy Intake;Female;Hemochromatosis/th [Therapy];Hepatic Encephalopathy/th [Therapy];Hepatolenticular Degeneration/th [Therapy];Humans;Lactulose/tu [Therapeutic Use];*Liver Cirrhosis/th [Therapy];Liver Cirrhosis, Biliary/dt [Drug Therapy];Male;Middle Aged;Mineralocorticoid Receptor Antagonists/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];Potassium/me [Metabolism];Vitamin B 12/tu [Therapeutic Use];0 (Dietary Fats);0 (Dietary Proteins);0 (Diuretics);0 (Mineralocorticoid Receptor Antagonists);11041-12-6 (Cholestyramine Resin);4618-18-2 (Lactulose);GNN1DV99GX (Penicillamine);P6YC3EG204 (Vitamin B 12);RWP5GA015D (Potassium)","Morl, M.",1981,May,,0,0,
854,Computed tomography in Wilson disease,"Computed tomography (CT) was performed on five patients with the ""cerebral form"" and one with the ""hepatic form"" of Wilson disease. The diagnosis was confirmed biochemically and by the presence of Kayser-Fleischer rings in all cases. In four patients, CT was done at the time of diagnosis; in two of these patients, the scan was repeated at intervals after initiation of treatment. CT was abnormal in all patients with the ""cerebral form."" All CT abnormalities were of low density and were not changed by contrast infusion. The abnormalities involved the basal ganglia in all five patients; in two patients, areas of low density also involved the cerebellar nuclei and surrounding white matter. CT abnormalities, however, did not always correlate well with the clinical state and in two patients, CT findings worsened despite successful cupruresis. The one patient with the ""hepatic form"" had no CT abnormalities.","Adolescent;Adult;*Brain/dg [Diagnostic Imaging];Diatrizoate Meglumine;Female;*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];*Tomography, X-Ray Computed;3X9MR4N98U (Diatrizoate Meglumine);GNN1DV99GX (Penicillamine)","Harik, S. I.;Post, M. J.",1981,Jan,,0,0,
855,The metabolism and pharmacology of D-penicillamine in man,"D-penicillamine is rapidly absorbed from the intestine and appears in plasma as free penicillamine, cysteine-penicillamine disulfide, and penicillamine disulfide. Penicillamine binds firmly to serum and tissue proteins. The urinary excretion of S-methyl-D-penicillamine, cysteine-penicillamine disulfide, penicillamine disulfide, and a newly identified metabolite, homocysteine-penicillamine disulfide, has been quantitated for patients with rheumatoid arthritis, cystinuria, and Wilson's disease. Fifty percent of an oral dose is excreted in the feces, but the metabolites have not yet been fully characterized. The pharmacologic effects of D-penicillamine are associated with disulfide bond formation or cleavage, thiazolidine formation, and metal chelation. [References: 48]","Absorption;Arthritis, Rheumatoid/dt [Drug Therapy];Cystinuria/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/me [Metabolism];Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Receptors, Drug;0 (Receptors, Drug);GNN1DV99GX (Penicillamine)","Perrett, D.",1981,Jan-Feb,,0,0,
856,The discovery of the therapeutic use of D-penicillamine,"An account is given of the identification of penicillamine in human urine by chromatographic and analytical techniques. At that time this observation appeared to be of esoteric interest only. Some years later, working at the Thorndike Memorial Laboratory at the Boston City Hospital, it occurred to me that the formula of this compound was ideally suited for use as a copper chelating agent for the treatment of Wilson's disease. The subsequent work leading to the acceptance of penicillamine as an important new therapy and also as to its mode of action is given with illustrations of some key experiments and with reference to the first patient ever treated with this drug.","Adolescent;Chelating Agents/me [Metabolism];Copper/me [Metabolism];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];History, 20th Century;Humans;Ninhydrin/ur [Urine];Penicillamine/hi [History];Penicillamine/ip [Isolation & Purification];Penicillamine/me [Metabolism];*Penicillamine/tu [Therapeutic Use];Sulfhydryl Compounds/tu [Therapeutic Use];0 (Chelating Agents);0 (Sulfhydryl Compounds);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);HCL6S9K23A (Ninhydrin)","Walshe, J. M.",1981,Jan-Feb,,0,0,
857,Copper penicillaminate for rheumatoid arthritis?,,"*Arthritis, Rheumatoid/dt [Drug Therapy];Cell Division/de [Drug Effects];Copper/ad [Administration & Dosage];Copper/pd [Pharmacology];Copper/tu [Therapeutic Use];Copper/to [Toxicity];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ad [Administration & Dosage];Penicillamine/pd [Pharmacology];*Penicillamine/tu [Therapeutic Use];Penicillamine/to [Toxicity];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Scheinberg, I. H.",1981,Jan-Feb,,0,0,
858,Penicillamine and the SLE syndrome,"Penicillamine-induced systemic lupus erythematosus (SLE) and penicillamine-immune complex nephritis are histologically and serologically distinct. One hundred and twenty patients with Wilson's disease treated with penicillamine have been analyzed. Eight developed the serologic changes of SLE; in 4, it was necessary to discontinue treatment. In addition, 6 patients developed immune complex nephritis, which necessitated discontinuing treatment. All but 1 have since been managed on triethylene tetramine 2HCl (Trien).","Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lupus Erythematosus, Systemic/ci [Chemically Induced];Lupus Erythematosus, Systemic/di [Diagnosis];Lupus Erythematosus, Systemic/pp [Physiopathology];Male;Manganese/bl [Blood];Manganese/me [Metabolism];*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);42Z2K6ZL8P (Manganese);GNN1DV99GX (Penicillamine)","Walshe, J. M.",1981,Jan-Feb,,0,0,
859,Recurrent abdominal colic as the sole symptom of Wilson's Disease: case report,,"Ceruloplasmin/an [Analysis];Child;*Colic/di [Diagnosis];Colic/dt [Drug Therapy];Copper/bl [Blood];Copper/ur [Urine];Diagnosis, Differential;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dh [Diet Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Function Tests;Male;Penicillamine/tu [Therapeutic Use];Phobic Disorders/di [Diagnosis];Recurrence;Schools;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Rao, S. V.;Greene, C. A.;Ellinoff, V.",1981,Aug,,0,0,
860,Penicillamine-induced dermal fragility in Wilson's disease (hepato-lenticular degeneration),,Adult;*Drug Eruptions/et [Etiology];Drug Eruptions/pa [Pathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];Skin/pa [Pathology];GNN1DV99GX (Penicillamine),"Shaw, M.;Jarrett, A.",1981,Jul,,0,0,
861,Penicillamine: twenty-five years later,,"Arthritis, Juvenile/dt [Drug Therapy];Arthritis, Rheumatoid/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Crawhall, J. C.",1980,Aug,,0,0,
862,Long-term penicillamine therapy for Wilson's disease,,Adult;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Haggstrom, G. D.;Hirschowitz, B. I.;Flint, A.",1980,Apr,,0,0,
863,[Use of penicillamine in Wilson-Konovalov disease],,Adolescent;Adult;Child;Copper/bl [Blood];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver/pp [Physiopathology];Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];Time Factors;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Vakharlovskii, V. G.;Nikitina, L. I.;Bondarchuk, A. N.",1980,Jan,,0,0,
864,[Wilson' disease: rapid diagnosis and differentiation of heterozygous and homozygous carriers with 64CuCl2 (author's transl)],"In the modified radiocopper test, a constant amount of copper and not of radioactivity is injected, a difference being made between males and females. The rate of incorporation of 64Cu into caeruloplasmin and urinary excretion of nuclides is measured. It is a method with low radiation exposure, providing a definite diagnosis after 30 hours. This was demonstrated in 27 homozygous patients, 30 parents and 33 siblings, and 25 controls: a clear-cut diagnosis was made in all untreated homozygous patients. In five of eight patients treated with D-penicillamine for several years, the values were in the range of heterozygotes, so that the test makes treatment control possible. The recognition of heterozygous carriers is interfered with by contraceptives and infections. The results in control subjects were all widely outside the range for patients with Wilson's disease.",Adolescent;Adult;*Carrier State/di [Diagnosis];Ceruloplasmin/me [Metabolism];Child;Copper;Female;*Hepatolenticular Degeneration/di [Diagnosis];Heterozygote;Homozygote;Humans;Male;Radioisotopes;Time Factors;0 (Radioisotopes);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin),"Wesch, H.;Przuntek, H.;Feist, D.",1980,Apr 04,https://dx.doi.org/10.1055/s-2008-1070692,0,0,
865,Copper chelating agents. A comparison of cupruretic responses to various tetramines and D-penicillamine,"Toxic or hypersensitivity reactions occur frequently with D-penicillamine therapy. Therefore there is a need for effective, well-tolerated alternative chelating agents to control the copper accumulation which occurs in Wilson's disease and some other chronic liver diseases. A group of tetramines (linear and macrocyclic) was surveyed for cupruretic activity and compared to D-penicillamine. 2,3,2-Tetramine was the most effective agent when given either by gavage or intravenously. It was more effective than 2,2,2-tetramine (trien) or D-penicillamine and, in addition, induced a more prolonged cupruresis. Despite their higher formation constants for copper, the macrocyclic tetramines did not induce a significant cupruresis. In this study, the 2,3,2-tetramine was the most effective agent for inducing a cupruresis in both normal and copper-loaded rats. If well tolerated by humans, it could become a useful agent for management of disorders characterized by copper accumulation.",Animals;*Chelating Agents;Copper/me [Metabolism];*Copper/pd [Pharmacology];Copper/ur [Urine];Hepatolenticular Degeneration/ur [Urine];Humans;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];*Polyamines/pd [Pharmacology];Polyamines/tu [Therapeutic Use];Rats;0 (Chelating Agents);0 (Polyamines);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Borthwick, T. R.;Benson, G. D.;Schugar, H. J.",1980,Apr,,0,0,
866,Clinical chemistry of trace elements,,"Acrodermatitis/ge [Genetics];Adult;Animals;Child;Congenital Abnormalities/et [Etiology];Copper/df [Deficiency];*Copper/me [Metabolism];Diet;Diet, Reducing/st [Standards];Female;Food Handling;Food, Formulated/st [Standards];Gastrointestinal Diseases/me [Metabolism];Hepatolenticular Degeneration/me [Metabolism];Humans;Infant;Infant Food;Infant, Newborn;Menkes Kinky Hair Syndrome/et [Etiology];Milk, Human/an [Analysis];Parenteral Nutrition, Total/st [Standards];Pregnancy;Renal Dialysis;Trace Elements/an [Analysis];*Trace Elements/me [Metabolism];Zinc/df [Deficiency];*Zinc/me [Metabolism];0 (Trace Elements);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Clayton, B. E.",1980,,,0,0,
867,[Wilson's disease in the German Democratic Republic. III. Diagnosis and therapy],"Taking into consideration the manifold symptomatology of Wilson's disease on the one hand and the necessity of an early--possibly already at the asymptomatic stage before the 6th year of life--diagnostic ascertainment on the other hand, the diagnostic approach performed in the GDR is described. Furthermore, the directives of treatment and the successes of treatment are discussed as well as the various side-effects of the D-penicillamine therapy described, in which case the severe nephrotic syndromes are particularly considered.",Adult;Ceruloplasmin/df [Deficiency];Child;*Copper/me [Metabolism];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Heterozygote Detection;Humans;Immune Complex Diseases/ci [Chemically Induced];Infant;Male;Nephritis/ci [Chemically Induced];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Lossner, J.;Storch, W.;Bachmann, H.;Biesold, D.;Kuhn, H. J.",1980,Feb 15,,0,1,
868,Triethylene tetramine dihydrochloride toxicity in primary biliary cirrhosis,"Triethylene tetramine dihydrochloride (trien) is a copper chelating agent used as the alternative drug of choice in the treatment of Wilson's disease. Because of its apparent safety, we have used the drug in 4 patients with primary biliary cirrhosis in whom penicillamine had to be withdrawn because of serious side effects. Trien is an effective cupruretic drug in primary biliary cirrhosis, but its use is limited by the occurrence of side effects that occurred in all 4 patients. Three patients developed gastrointestinal side effects, and one of these patients developed a skin rash. The 4th patient developed acute rhabdomyolysis within 48 hr of receiving the first dose of the drug. One patient tolerated therapy for 20 wk, and, although her liver copper concentration did not show a marked fall, aspartate transaminase levels fell, and her IgM concentration fell to normal. Trien is an unsuitable copper chelating drug in primary biliary cirrhosis, although it remains the alternative drug of choice in Wilson's disease.","Adult;*Anorexia/ci [Chemically Induced];*Chelating Agents/ae [Adverse Effects];Copper/me [Metabolism];*Drug Eruptions/et [Etiology];*Ethylenediamines/ae [Adverse Effects];*Feeding and Eating Disorders/ci [Chemically Induced];Female;*Gastritis/ci [Chemically Induced];Humans;*Liver Cirrhosis, Biliary/dt [Drug Therapy];Liver Cirrhosis, Biliary/me [Metabolism];Middle Aged;*Muscular Diseases/ci [Chemically Induced];*Trientine/ae [Adverse Effects];0 (Chelating Agents);0 (Ethylenediamines);789U1901C5 (Copper);SJ76Y07H5F (Trientine)","Epstein, O.;Sherlock, S.",1980,Jun,,0,0,
869,Copper and the liver,,"Acute Disease;Adult;Age Factors;Animals;Bufo marinus;Carcinoma, Hepatocellular/me [Metabolism];Chemical and Drug Induced Liver Injury/et [Etiology];Child;Cholestasis/me [Metabolism];Chronic Disease;Copper/an [Analysis];Copper/df [Deficiency];*Copper/me [Metabolism];Copper/ph [Physiology];Disease Models, Animal;Dogs;Female;Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Histocytochemistry;Humans;India;Indicators and Reagents;Infant;*Liver/me [Metabolism];Liver/ul [Ultrastructure];Liver Neoplasms/me [Metabolism];Male;Metalloproteins/me [Metabolism];Middle Aged;Mitochondria, Liver/de [Drug Effects];Penicillamine/tu [Therapeutic Use];0 (Indicators and Reagents);0 (Metalloproteins);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Sternlieb, I.",1980,Jun,,0,0,
870,Clinical spectrum of Wilson's disease (hepatolenticular degeneration),"Fifty-eight patients with Wilson's disease are reviewed, of whom 25 symptomatic patients experienced liver disease first and 28, brain disease. Ten of these patients presented with liver disease alone, 19 with brain disease alone, and 24 with evidence of both liver and brain disease. The remaining five were discovered as asymptomatic siblings of known patients. Three of the patients with hepatic presentation and one with neurologic presentation later experienced the other type of symptomatology, bringing the total number of patients with mixed disease to 28. Of the 44 patients with brain disease, 12 presented primarily with extrapyramidal findings, 6 with cerebellar findings, and 17 with both; pseudobulbar findings were noted in 9 patients, all of whom had other symptoms of severe nervous system disease. In addition to these presentations, in an appreciable number of patients the first symptoms were of a mental or emotional disorder. Disease of other organ systems, such as the joints and kidneys, also occurred but infrequently. Where adequate family information was available, 13 of 65 siblings (20%) were known to have had or were suspected of having had Wilson's disease. This is consistent with the autosomal-recessive pattern of inheritance.","Adolescent;Adult;Brain Diseases/et [Etiology];Child;Copper/me [Metabolism];Cornea;Dimercaprol/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];Humans;Hypertension, Portal/et [Etiology];Liver Diseases/et [Etiology];Male;Mental Disorders/et [Etiology];Middle Aged;Penicillamine/tu [Therapeutic Use];Pigmentation;Prognosis;Syndrome;0CPP32S55X (Dimercaprol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Dobyns, W. B.;Goldstein, N. P.;Gordon, H.",1979,Jan,,0,0,
871,Computerized cranial tomography in Wilson disease,"Hepatolenticular degeneration (Wilson disease) is suspected by the clinical picture and confirmed by characteristic laboratory demonstration of impaired copper metabolism. Three patients with Wilson disease involving the basal ganglia were shown to have abnormalities on computerized tomography (CT) scan, whereas four other patients without signs of cerebral involvement had normal brain scans. Wilson disease may be added to the long list of diseases to which the EMI scan may make a useful diagnostic contribution.","Adult;Basal Ganglia/dg [Diagnostic Imaging];Ceruloplasmin/an [Analysis];Female;*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Neurocognitive Disorders/di [Diagnosis];Penicillamine/tu [Therapeutic Use];*Tomography, X-Ray Computed;EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Nelson, R. F.;Guzman, D. A.;Grahovac, Z.;Howse, D. C.",1979,Jun,,0,0,
872,[Treatment of liver cirrhosis and its complications],,"Ascites/dt [Drug Therapy];Azathioprine/tu [Therapeutic Use];Barbiturates/tu [Therapeutic Use];Hemochromatosis/dt [Drug Therapy];Hepatic Encephalopathy/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Cirrhosis/co [Complications];*Liver Cirrhosis/dt [Drug Therapy];Liver Cirrhosis, Alcoholic/dt [Drug Therapy];Penicillamine/tu [Therapeutic Use];0 (Barbiturates);GNN1DV99GX (Penicillamine);MRK240IY2L (Azathioprine)","Talke, H.",1979,Apr 15,,0,0,
873,The management of Wilson's disease with trienthylene tetramine 2HC1 (Trien 2HC1),,Drug Hypersensitivity;*Ethylenediamines/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Male;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Trientine/tu [Therapeutic Use];0 (Ethylenediamines);GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Walshe, J. M.",1979,,,0,0,
874,[Wilson's liver disease in children and adolescents (author's transl)],"Hepatic symptoms are usually the first in Wilson's disease of children and adolescents, while neurologic symptoms and the corneal ring are still missing. Liver lesions due to copper accumulation may develop throughout years without clinical symptoms or biochemical abnormalities. Hemolytic jaundice or gastrointestinal bleeding are the presenting symptoms in some cases. In spite of being a rare syndrom Wilson's disease ought to be considered after hepatitis B or autoimmune liver disease have been excluded as causes of juvenile cirrhosis of the liver. If life-long treatment with D-penicillamin is started in an early stage of Wilson's disease, prognosis is rather good.","Adolescent;Biopsy, Needle;Ceruloplasmin/an [Analysis];Child;Diagnosis, Differential;Female;Hepatitis B/di [Diagnosis];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/et [Etiology];Hepatolenticular Degeneration/im [Immunology];Humans;Liver/pa [Pathology];Male;Prognosis;EC 1-16-3-1 (Ceruloplasmin)","Feist, D.;Wesch, H.",1979,Sep,,0,0,
875,The formation and nature of the mixed valence copper-D-penicillamine-chloride cluster in aqueous solution and its relevance to the treatment of Wilson's disease,"Complex formation between D-penicillamine (Pen) and copper(II) ions has been studied under simulated physiological conditions in both the presence and absence of the blood plasma constituents albumin, alanine, histidine, and zinc(II). Chromatographic and uv/vis and electron spin resonance (esr) spectroscopic methods were used. The major species formed, at neutral pH and 0.15 mol dm-3 NaCl, is the violet species which is shown to have the same stoichiometry as the recently reported solid-state complex, i.e., [Cu8I Cu6II (Pen)12 Cl] 5-. The rate of formation of this species (MVC) is shown to be dependent on the Cu concentration, Cu:Pen ratio, relative Cl- ion concentration, pH, and temperature. Formation is inhibited by the presence of O2 and biological chelates. At the concentration levels found in blood plasma it is unlikely that the MVC ion has any significance in the therapeutic action of penicillamine in the treatment of Wilson's disease. Reexamination of the aqueous Cu-albumin-pen system reinforces earlier findings that pen is unable to mobilize Cu that is bound to albumin. Significant binding of pen to the protein is observed is not related to any protein-bound copper ions. Evidence that ternary complexes of the type amino acid-Cu-Pen can form in blood plasma is presented. These are unlikely, however, to be physiologically significant and the copper depletion induced by Pen in Wilson's disease cases must be elsewhere than in the blood plasma compartment.",Chemical Phenomena;Chemistry;*Copper;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Kinetics;Penicillamine/tu [Therapeutic Use];*Penicillamine;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Laurie, S. H.;Prime, D. M.",1979,Nov,,0,0,
876,"2,3,2-tetramine--a potent cupruretic agent",,Animals;*Chelating Agents;*Copper/ur [Urine];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Polyamines/pd [Pharmacology];Polyamines/ur [Urine];Rats;0 (Chelating Agents);0 (Polyamines);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Borthwick, T. R.;Benson, G. D.;Schugar, H. J.",1979,Oct,,0,0,
877,"""Lumpy-bumpy"" elastic fibers in the skin and lungs of a patient with a penicillamine-induced elastosis perforans serpiginosa","Penicillamine-induced cutaneous elastosis perforans serpiginosa associated with a large air-cyst in the right lung is described in a 29-year-old female patient with Wilson disease. Identical light and electron-microscopic changes were present in both dermal and pulmonary elastic tissue, suggesting a disseminated drug-induced cutaneo-visceral elastosis. Lung cysts have not been previously reported in association with long term penicillamine treatment. The electron-microscopic morphology of the elastic fibers was found to be ""specific"" enough to allow separation of penicillamine-induced elastosis perforans serpiginosa from other forms of this disease.","Adult;*Cysts/ci [Chemically Induced];*Elastic Tissue/pa [Pathology];Elastic Tissue/ul [Ultrastructure];Female;Humans;*Lung/pa [Pathology];*Lung Diseases/ci [Chemically Induced];Lung Diseases/pa [Pathology];Microscopy, Electron;*Penicillamine/ae [Adverse Effects];*Skin/pa [Pathology];*Skin Diseases/ci [Chemically Induced];Skin Diseases/pa [Pathology];GNN1DV99GX (Penicillamine)","Bardach, H.;Gebhart, W.;Niebauer, G.",1979,Aug,,0,0,
878,Hepatic copper accumulation in primary biliary cirrhosis,"Hepatic copper accumulation is a regular feature of primary biliary cirrhosis (PBC). The levels are directly related to the clinical stage of the disease. Since the copper values in PBC are comparable to Wilson's disease, there is the potential for copper toxicity, although this is speculative since the two diseases differ in the binding, distribution, and intracellular localization of the copper. The involvement of copper toxicity in the progression of PBC is supported by the observation that the highest values occur in association with the hepatic failure that occurs in the advanced stage.Corticosteroid therapy appears to decrease hepatic copper levels in PBC. Although this therapy does not invariably lower the hepatic Cu content in patients with PBC, it does so in many individuals. Therapeutic trials with d-penicillamine are in progress. When results are available they will guide us in the management of individual patients with PBC. In the meantime, dietary copper should be restricted as is done in management of Wilson's disease.","Adrenal Cortex Hormones/tu [Therapeutic Use];*Copper/me [Metabolism];Humans;*Liver/me [Metabolism];Liver Cirrhosis, Biliary/dt [Drug Therapy];*Liver Cirrhosis, Biliary/me [Metabolism];Penicillamine/tu [Therapeutic Use];0 (Adrenal Cortex Hormones);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Benson, G. D.",1979,Jan-Feb,,0,0,
879,[Spontaneous and DL-penicillamine-induced renal copper excretion in liver diseases (author's transl)],"The levels of cupriuresis before and after DL-Penicillamine have been investigated in 168 cases. The mean copper excretion before Penicillamine in chronic activ liver disease, chronic persistant hepatitis, cirrhosis and in transitional cases of aggressiv chronic hepatitis and primary biliary cirrhosis ranged from 29 gamma to 48 gamma/24 hr.; however, in some cases the daily copper excretion exceeds 100 gamma, as well in subjects with liver disease as in normals too. After ingesting 900 mg DL-Penicillamine the mean values of cupriuresis ranged from 500 gamma to 600 gamma/24 hr. Abnormal results were found in about 15% of those subjects with liver diseases; in only two of 20 cases with hypercupruria after Penicillamine Wilson's Disease was established.",*Copper/ur [Urine];Hepatitis/ur [Urine];Humans;Liver Cirrhosis/ur [Urine];*Liver Diseases/ur [Urine];*Penicillamine/pd [Pharmacology];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Friedrich, K.;Henning, H.",1979,Mar,,0,0,
880,Laboratory measures of copper metabolism in the differentiation of chronic active hepatitis and Wilson disease in children,"The accuracy of the serum ceruloplasmin level in distinguishing chronic active hepatitis from Wilson disease was compared to the 24-hour urinary copper excretion and hepatic copper content in 20 untreated patients with chronic active hepatitis and 25 with Wilson disease. Serum ceruloplasmin levels were decreased in five patients (25%) with chronic active hepatitis and were normal in seven patients (28%) with Wilson disease at the time of diagnosis. The 24-hour urinary copper excretion failed to provide accurate discrimination between the two groups, being elevated in all patients with Wilson disease and in five of eight patients with chronic active hepatitis studied. All patients with Wilson disease had hepatic copper levels greater than 400 microgram/gm dry weight, whereas patients with chronic active hepatitis had levels less than 300 microgram/gm dry weight. The discriminatory value of hepatic copper concentration makes this the most reliable test for differentiating chronic active hepatitis and Wilson disease in children and adolescents. The serum ceruloplasmin level may not be significantly accurate for definitive diagnosis in this age group.","Adolescent;Adult;Azathioprine/tu [Therapeutic Use];*Ceruloplasmin/an [Analysis];Child;Child, Preschool;Chronic Disease;*Copper/an [Analysis];Copper/me [Metabolism];Diagnosis, Differential;Diagnostic Errors;*Hepatitis/di [Diagnosis];Hepatitis/dt [Drug Therapy];Hepatitis/me [Metabolism];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/an [Analysis];Penicillamine/tu [Therapeutic Use];Prednisone/tu [Therapeutic Use];Pyridoxine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine);MRK240IY2L (Azathioprine);VB0R961HZT (Prednisone)","Perman, J. A.;Werlin, S. L.;Grand, R. J.;Watkins, J. B.",1979,Apr,,0,0,
881,Wilson's disease,,"Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Humans;*Hypertension, Portal/et [Etiology];Hypertension, Portal/su [Surgery];*Penicillamine/tu [Therapeutic Use];*Portacaval Shunt, Surgical/ae [Adverse Effects];GNN1DV99GX (Penicillamine)","Grand, R. J.",1979,Apr,,0,0,
882,Trace elements in human nutrition,"Clinical recognition of the role of trace elements in human nutrition is increasing. Heretofore, many clinicians felt that the development of deficiency states was not likely except in very extreme conditions because the presence of trace elements in nature was so ubiquitous. The increased use of total parenteral nutrition seems to have made this viewpoint untenable. The recognition of additional genetic diseases of trace element metabolism such as Menkes' kinky hair syndrome and acrodermatitis enteropathica has also served to focus clinical attention on trace elements. As time passes, no doubt, additional diseases of trace element metabolism will be recognized. [References: 57]","Aging;Chelating Agents/tu [Therapeutic Use];Child, Preschool;Copper/df [Deficiency];Copper/me [Metabolism];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant;Manganese/me [Metabolism];Menkes Kinky Hair Syndrome/dt [Drug Therapy];*Nutritional Physiological Phenomena;Proteins/me [Metabolism];Socioeconomic Factors;Tissue Distribution;Trace Elements/me [Metabolism];*Trace Elements;Zinc/bl [Blood];Zinc/df [Deficiency];Zinc/me [Metabolism];0 (Chelating Agents);0 (Proteins);0 (Trace Elements);42Z2K6ZL8P (Manganese);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Burch, R. E.;Hahn, H. K.",1979,Sep,,0,0,
883,[Unusual and different clinical aspects of Wilson's disease in 2 sisters],,"Acute Kidney Injury/et [Etiology];Anemia, Hemolytic/et [Etiology];Chelating Agents/tu [Therapeutic Use];Child;Copper/me [Metabolism];Disseminated Intravascular Coagulation/et [Etiology];Female;Gastrointestinal Hemorrhage/bl [Blood];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Humans;Jaundice/et [Etiology];Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Bassetti, D.;Giacchino, R.;Ciravegna, B.;Ferrea, G.",1979,Oct 31,,0,0,
884,Drugs: distamine,,"Adult;Arthritis, Rheumatoid/dt [Drug Therapy];Child;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lead Poisoning/dt [Drug Therapy];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Hopkins, S. J.",1979,Jul 19,,0,0,
885,Reversible cutis laxa due to maternal D-penicillamine treatment,,"*Cutis Laxa/ci [Chemically Induced];Female;*Fetus/de [Drug Effects];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Infant, Newborn;*Infant, Newborn, Diseases/ci [Chemically Induced];Male;Maternal-Fetal Exchange;*Penicillamine/ae [Adverse Effects];Pregnancy;Remission, Spontaneous;GNN1DV99GX (Penicillamine)","Linares, A.;Zarranz, J. J.;Rodriguez-Alarcon, J.;Diaz-Perez, J. L.",1979,Jul 07,,0,0,
886,Ophthalmoscopic changes in a patient with Wilson's disease during long-term penicillamine therapy,The development of retinal pigment epithelial defects in a young patient with Wilson's disease after long-term penicillamine therapy is described. It is hypothesized that decreased copper availability secondary to penicillamine therapy may result in defective elastin within the lamina of Bruch with resultant defects in the overlying retinal pigment epithelium.,Adult;Copper/df [Deficiency];Female;*Fundus Oculi;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Pigment Epithelium of Eye/de [Drug Effects];Retinal Diseases/ci [Chemically Induced];Time Factors;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Dingle, J.;Havener, W. H.",1978,Sep,,0,0,
887,Don't forget Wilson's disease,,"Diagnosis, Differential;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Liver Diseases/di [Diagnosis];Middle Aged;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)",Anonymous,1978,Nov 18,,0,0,
888,"The urinary excretion of radiocopper in presymptomatic and symptomatic Wilson's disease, heterozygotes and controls: its significance in diagnosis and management","Radiocopper (64Cu, 67CU), given intravenously, has been used to study the pattern of excretion of copper in patients with presymptomatic, symptomatic and treated Wilson's disease, together with heterozygotes for the Wilson's disease gene and a control group of patients with a variety of neurological lesions mimicking Wilson's disease. Urine was collected for three periods after injection, 0 to 8 hours, 8 to 24 hours, at which time a test dose of penicillamine was given, and from 24 to 30 hours. Stable (endogenous) copper was also estimated on these samples and specific activity was determined. This was multiplied by a correction factor to allow for variations in dose and body weight. The findings for stable copper in urine were largely predictable. Controls and heterozygotes had the least copper excretion, the amounts rising in the presymptomatic to a peak in the symptomatic patients. Institution of therapy was associated with a fall in copper excretion pro rata with time. The most important radiochemical findings were as follows. Heterozygotes excreted less of the injected copper than controls both under basal conditions and after penicillamine. Presymptomatic patients excreted less radiocopper than heterozygotes after penicillamine although the excretion during the basal 24 hour period was very much greater. Patients with symptomatic Wilson's disease had by far the highest excretion of radiocopper in all three time periods which fell after treatment, pro rata with time, as had been found for stable copper. These results were subjected to computer analysis. There was no overlap between the various groups with the exception of a single control subject who had combined pyramidal and extrapyramidal system degeneration of obscure aetiology. This patient was classified by the computer study as 'heterozygote'. These findings lend further support to the hypothesis that the loss of a single gene for copper balance can be detected with a high degree of accuracy and also that presymptomatic patients can be selected from a sibship for prophylactic treatment without the risk of subjecting healthy heterozygotes to unnecessary and potentially hazardous long-term therapy.",Adolescent;Adult;Child;*Copper/me [Metabolism];Copper/ur [Urine];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Heterozygote;Humans;Male;Penicillamine/pd [Pharmacology];Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Gibbs, K.;Hanka, R.;Walshe, J. M.",1978,Jul,,0,0,
889,Wilson's disease and monoamines,,Adult;*Hepatolenticular Degeneration/cf [Cerebrospinal Fluid];Hepatolenticular Degeneration/dt [Drug Therapy];*Homovanillic Acid/cf [Cerebrospinal Fluid];Humans;*Hydroxyindoleacetic Acid/cf [Cerebrospinal Fluid];Male;Penicillamine/tu [Therapeutic Use];*Phenylacetates/cf [Cerebrospinal Fluid];0 (Phenylacetates);54-16-0 (Hydroxyindoleacetic Acid);GNN1DV99GX (Penicillamine);X77S6GMS36 (Homovanillic Acid),"Nijeholt, J. L.;Korf, J.",1978,Sep,,0,0,
890,Diagnostic dilemmas of Wilson's disease: diagnosis and treatment,"Wilson's disease, an autosomal recessive disorder of copper metabolism, may defy diagnosis in children. The classical triad of Kayser-Fleischer rings, neurologic dysfunction, and hypoceruloplasminemia may be absent. Patients may be seen initially with acute or chronic hepatitis, hemolytic anemia, or neurologic dysfunction. Guidelines are presented for diagnosis of Wilson's disease based on a review of 25 pediatric and adolescent patients. A high index of suspicion in necessary so that therapy with penicillamine may be begun before irreversible liver or neurologic damage occurs. The prognosis is excellent when diagnosis and treatment are established early.","Adolescent;Adult;Copper/me [Metabolism];Diagnosis, Differential;Female;Hemolysis;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dh [Diet Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Humans;Liver Function Tests;Male;Penicillamine/tu [Therapeutic Use];Prognosis;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Werlin, S. L.;Grand, R. J.;Perman, J. A.;Watkins, J. B.",1978,Jul,,0,0,
891,Hematologic (cytopenic) manifestations of Wilson's disease (hepatolenticular degeneration),"The records of 54 consecutive patients with Wilson's disease seen at the Mayo Clinic from 1952 through early 1977 were reviewed to determine the frequency fo hematologic abnormalaties in their evaluation. Leukopenia and thrombocytopenia sometimes have been ascribed to treatment with D-penicillamine and its toxicity; however, we have found cytopenia to be a frequent finding in the presenting laboratory data of patients with Wilson's disease. Twenty-eight patients (52%) had thrombocytopenia and 16 of these patients (30% of the total) also had leukopenia. Severe, acute, intermittent hemolytic episodes were the initial and only presenting complaint of one patient. Six of the patients with significant cytopenias had splenectomy, and in all cases the peripheral blood counts returned to normal values. Long-term treatment with D-penicillamine improved the hepatic and neurologic dysfunction in most patients; however, the cytopenias remained unchanged except in three patients (treated 2, 5, and 10 years).",Female;*Hemorrhagic Disorders/et [Etiology];*Hepatolenticular Degeneration/co [Complications];Hepatomegaly/et [Etiology];Humans;Leukopenia/co [Complications];Leukopenia/et [Etiology];Leukopenia/su [Surgery];Liver Function Tests;Male;Splenectomy;Splenomegaly/et [Etiology];Thrombocytopenia/co [Complications];Thrombocytopenia/et [Etiology];Thrombocytopenia/su [Surgery],"Hogland, H. C.;Goldstein, N. P.",1978,Aug,,0,0,
892,Oral zinc in Wilson's disease,,"Administration, Oral;Adolescent;Copper/ad [Administration & Dosage];Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Injections, Intravenous;Isotope Labeling;Radioisotopes;*Zinc/ad [Administration & Dosage];0 (Radioisotopes);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Hoogenraad, T. U.;Van den Hamer, C. J.;Koevoet, R.;Korver, E. G.",1978,Dec 09,,0,0,
893,Failure of L-dopa to relieve activated rigidity in Parkinson's disease,"Rigidity in Parkinson patients can be easily quantitated by determining net work required to passively flex and extend the forearm through an arc of 100 degrees. Rigidity thus measured can be subdivided into two very distinct types, resting and activated. Resting rigidity, measured while the patient is relaxed, responds to all effective therapeutic agents and correlates closely to degree of clinical improvement. Activated rigidity, measured during voluntary activity, is not relieved by any presently available medical treatment. It remains unchanged at pre-therapy levels even in patients who may temporarily appear to have dramatic improvement in clinical symptomatology. Longitudinal measurements made in hundreds of parkinson patients over intervals ranging from 5 to 15 years show continuing high levels of activated rigidity through the entire period of study. In marked contrast to our wide experience with parkinson patients is a single, well documented case of Wilson's disease who appears to have recovered completely both by clinical examination and by all of our machine measurements. This patient had high levels of extrapyramidal deficit, repeatedly measured over a period of four months when penicillamine therapy was being investigated. He then suddenly reverted to normal and returned to full time employment. High values of resting rigidity activated rigidity, akinesia and resting tremor all reverted to normal and have remained normal for the past 6 years. The implication of this study is that L-dopa and related treatments only mask the symptomatology of Parkinson's disease and are not retarding the underlying pathological process. Penicillamine, on the other hand, probably does relieve the destructive process in Wilson's disease and may in early cases, permanently relieve the extrapyramidal dysfunction.",Adult;Amantadine/tu [Therapeutic Use];Extrapyramidal Tracts/pp [Physiopathology];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Levodopa/tu [Therapeutic Use];Male;Middle Aged;Muscle Contraction;Parkinson Disease/dt [Drug Therapy];Parkinson Disease/pp [Physiopathology];*Parkinson Disease/th [Therapy];*Penicillamine/tu [Therapeutic Use];Thalamus/su [Surgery];46627O600J (Levodopa);BF4C9Z1J53 (Amantadine);GNN1DV99GX (Penicillamine),"Webster, D. D.;Mortimer, J. A.",1977,,,0,0,
894,Primary and secondary disturbances in trace element metabolism connected with genetic metabolic disorders,"Several primarily inherited disturbances of minerals and trace elements have been discovered within the last 20 years. Secondary disturbances of selenium and zinc induced by dietetic treatment of inborn errors of metabolism and by parenteral nutrition also came to our knowledge recently. Two main types of chronic or primary hypomagnesaemia are known which are caused either by impaired intestinal absorption or by false magnesium handling by the kidneys. In acrodermatitis enteropathica, an autosomal-recessive inherited disease leading to characteristic skin lesions, alopecia and dystrophy, low zinc concentrations of serum, urine and hair are measured. The intestinal absorption of zinc is reduced. In copper metabolism two inherited diseases are known with low serum and usually caerulosplasmin concentrations. In Menkes' steely hair syndrome (trichlpoliodystrophy) an intestinal net malabsorption of copper exists, whereas in Wilson's disease the copper contents of several organs are increased.","Adult;Child, Preschool;Copper/me [Metabolism];Humans;Infant;Intestinal Absorption;Magnesium/bl [Blood];*Metabolism, Inborn Errors/me [Metabolism];*Minerals/me [Metabolism];*Trace Elements/me [Metabolism];Zinc/me [Metabolism];0 (Minerals);0 (Trace Elements);789U1901C5 (Copper);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc)","Lombeck, I.;Bremer, H. J.",1977,,,0,0,
895,"Structure, properties, and function of a copper(I)-copper(II) complex of D-penicillamine: pentathallium(I) mu8-chloro-dodeca (D-penicillaminato)-octacuprate(I)hexacuprate(II) n-hydrate",,Chelating Agents;Chemical Phenomena;Chemistry;*Copper;Crystallography;Hepatolenticular Degeneration/dt [Drug Therapy];*Penicillamine;*Thallium;0 (Chelating Agents);789U1901C5 (Copper);AD84R52XLF (Thallium);GNN1DV99GX (Penicillamine),"Birker, P. J.;Freeman, H. C.",1977,Oct 12,,0,0,
896,Fulminant Wilson's disease with haemolysis and renal failure: copper studies and assessment of dialysis regimens,"Two girls, aged 12 and 17 years, presented with hepatocellular dysfunction and severe haemolysis due to Wilson's disease (hepatolenticular degeneration). This was accompanied by acute renal failure. In the absence of renal function sufficient for the urinary excretion of penicillamine, studies were performed to assess the potential of peritoneal dialysis, ascites removal by ultrafiltration-reinfusion, and haemodialysis as alternative excretory pathways for copper. The greatest amount of copper, as judged by rising bath concentrations, seemed to be eliminated with haemodialysis. But this was accompanied by a progressive increase in serum copper concentrations with rapid clinical and biochemical deterioration leading to death within 48 hours. A small amount of copper was lost with ascites removal. Significant amounts of copper were removed during peritoneal dialysis (36 mumol/day (2287 microgram/day)), although a clinical response was not evident before haemodialysis was introduced. The administration of penicillamine orally, intravenously, or intraperitoneally produced no measurable increase in copper excretion into the peritoneal dialysate. Hence peritoneal dialysis alone appears to offer the greatest potential benefit with regard to both eliminating copper and altering the course of this fulminant form of Wilson's disease.",*Acute Kidney Injury/co [Complications];Adolescent;Child;*Copper/me [Metabolism];Female;*Hemolysis;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Humans;Penicillamine/tu [Therapeutic Use];Peritoneal Dialysis;*Renal Dialysis;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Hamlyn, A. N.;Gollan, J. L.;Douglas, A. P.;Sherlock, S.",1977,Sep 10,,0,0,
897,Juvenile Wilson disease: unusual features in three cases,,Adolescent;Child;Copper/me [Metabolism];Eye Manifestations;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Penicillamine/tu [Therapeutic Use];Skin Manifestations;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Jaeken, J.;Proesmans, W.",1977,Apr-Jun,,0,0,
898,The ophthalmologic manifestations of Wilson's disease,"Fifty-three patients with Wilson's disease were studied with regard to ophthalmologic abnormalities. Of the 35 symptomatic patients initially seen and treated at the Mayo Clinic, 34 (97%) had Kayser-Fleischer rings and 6 (17%) had sunflower cataracts at the time of diagnosis. In patients followed for a year or more, penicillamine therapy resulted in improvement of the Kayser-Fleischer rings in 18 of 20 (90%) patients and total clearing of the sunflower cataracts in 4 of 5 patients. The specific pattern of copper deposition in Kayser-Fleischer rings and the improvement with treatment occurred along four reproducible stages. None of five asymptomatic siblings of patients with known Wilson's disease had Kayer-Fleischer rings at the time of initial study. In one (untreated) of the five, Kayser-Fleischer rings developed 20 months after the initial normal slit-lamp examination. The presence of Kayser-Fleischer rings, and the absence of other ophthalmologic signs (such as nystagmus, cranial nerve palsies, and other movement disorders), can be of great assistance in the diagnosis of Wilson's disease. Once the condition has been diagnosed, specific medical therapy with penicillamine and low-copper diet dramatically improves what would otherwise be an inevitably fatal course.",Adolescent;Adult;Child;Cornea/pa [Pathology];*Eye Manifestations;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Male;Middle Aged;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Wiebers, D. O.;Hollenhorst, R. W.;Goldstein, N. P.",1977,Jul,,0,0,
899,Pregnancy in Wilson's disease,"The effect of pregnancy has been studied in 10 mothers with Wilson's disease. Three were presymptomatic but had the typical biochemical lesion, two of these were receiving penicillamine treatment at the time of conception, the third had yet to be diagnosed. The remaining seven mothers had had symptoms of Wilson's disease and had been receiving treatment for periods ranging from two and a half to 19 years. These mothers had 15 pregnancies between them, 13 went to full term but two ended prematurely at 26 and 30 weeks. In only one did pregnancy have an unfavourable effect on the Wilson's disease; this mother had been on penicillamine for only two and a half years in a suboptimal dose because of drug induced thrombocytopoenia. In addition she had extensive oesophageal varices and pregnancy was complicated by toxaemia. The other nine patients remained well and two had three pregnancies each. On six occasions penicillamine was taken throughout pregnancy, but in seven it was discontinued from the sixth to the twelfth week. All 15 babies were normal but one died of extreme prematurity (26 weeks gestation). Pregnancy does not appear to be contraindicated in well treated Wilson's disease and penicillamine does not seem to pose an undue risk to the foetus.",Ceruloplasmin/an [Analysis];Copper/bl [Blood];Female;Fetal Blood;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Pregnancy;Pregnancy Complications/bl [Blood];*Pregnancy Complications/di [Diagnosis];Pregnancy Complications/dt [Drug Therapy];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1977,Jan,,0,0,
900,[Liver cirrhosis caused by genetic defects],,Adult;Bloodletting;Hemochromatosis/co [Complications];Hemochromatosis/di [Diagnosis];Hemochromatosis/th [Therapy];Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Liver Cirrhosis/ge [Genetics];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Morl, M.;Gabriel, L.",1977,Mar 25,,0,0,
901,Pregnancy and delivery in penicillamine treated patients with Wilson's disease,"Pregnancy and delivery of two patients with Wilson's disease are reported. Case 1 was a 20-year-old housewife who had been taking D-penicillamine fore more than 10 years and had remained asymptomatic except an episode of dissociative reaction. She apparently survived longer than any of her three sisters who died of the same disease. She discontinued the use of D-penicillamine by herself when she was at the 22nd week of pregnancy. Case 2 was a 32-year-old housewife who developed an episode of mental disorder of short circuit reaction type with mild neurological symptoms and Kayser-Fleischer rings after the prolonged interval of medication since the first pregnancy and delivery. Three months after the complete recovery of neuropsychiatric symptoms she was at the 12th week of pregnancy and withheld penicillamine from herself. During the pregnancy they had not revealed any exacerbation in terms of clinical and laboratory findings. Each of them was delivered of a healthy baby. Although the pregnancy and delivery of both patients were successful, the authors recommended that they should not prolong the interval of medication to protect themselves against the onset or relapse of the illness.","Adult;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Humans;*Labor, Obstetric;Liver/pa [Pathology];Maternal-Fetal Exchange;*Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications/dt [Drug Therapy];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Fukuda, K.;Ishii, A.;Matsue, Y.;Funaki, K.;Hoshiai, H.;Maeda, S.",1977,Nov,,0,0,
902,Hemolytic anemia in Wilson's disease. A report of three cases with transient increase in hemoglobin A2,Three patients with Wilson's disease and initial manifestations of intravascular hemolysis also had transient elevations of hemoglobin A2. It is important to recognize such manifestations in establishing an early diagnosis.,"Acute Disease;Adolescent;*Anemia, Hemolytic/co [Complications];Anemia, Hemolytic/di [Diagnosis];Ascites/di [Diagnosis];Copper/ur [Urine];Female;*Hemoglobin A/an [Analysis];*Hemoglobins/an [Analysis];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatomegaly/di [Diagnosis];Humans;Male;Penicillamine/tu [Therapeutic Use];0 (Hemoglobins);789U1901C5 (Copper);9034-51-9 (Hemoglobin A);GNN1DV99GX (Penicillamine)","Robitaille, G. A.;Piscatelli, R. L.;Majeski, E. J.;Gelehrter, T. D.",1977,May 30,,0,0,
903,[Wilson's disease],,Adult;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Humans;Male;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Morl, M.;Gabriel, L.",1977,Jul 10,,0,0,
904,Hepatolenticular degeneration (Wilson's disease) and pregnancy. A review and report of a case,This article presents a case report of Wilson's disease in pregnancy and a review of this entity during gestation. Biochemical and pathological data are reviewed and current treatment is discussed. Pertinent questions of interest to the obstetrician are indicated with reference to Wilson's disease. [References: 99],"Adolescent;Adult;Animals;Ceruloplasmin/bl [Blood];Copper/me [Metabolism];Estrogens/tu [Therapeutic Use];Female;Fertility;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Hypertension, Renal/co [Complications];Infant, Newborn;Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications/me [Metabolism];0 (Estrogens);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Toaff, R.;Toaff, M. E.;Peyser, M. R.;Streifler, M.",1977,Aug,,0,0,
905,Ocular manifestations of Wilson's disease in Iran,"Within the last 5 years, 25 proved cases of hepato-lenticular degeneration (Wilson's disease) have been seen at the Children's Hospital Medical Center affiliated to Tehran University. The disease manifested abnormal copper metabolism in the following respects: (1) Hypoceruloplasminaemia was present: (2) 24-hr urinary copper excretion was low; (3) Tissue concentration of copper was high; (4) Treatment with penicillamine led to increased copper excretion in the urine and usually to relief of symptoms. The ophthalmologist cannot always assist the paediatrician in diagnosis, but fourteen of the 25 patients showed a Kayser-Fleischer ring and these were all in the older age groups. The following conclusions were drawn: (1) The incidence of Wilson's disease in Iran is high; (2) Penicillamine treatment may be successful; (3) Any young person with kidney, liver, or neurological disease of uncertain aetiology should have a detailed ophthalmological examination.","Adolescent;Adult;Child;Child, Preschool;*Cornea/pa [Pathology];Descemet Membrane/pa [Pathology];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration;Humans;Iran;Male;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Kashani, A. A.",1977,Apr,,0,0,
906,The peroxisomes of human hepatocytes,"In an ultrastructural study of human liver biopsy specimens we found that peroxisomes are regularly present in normal human hepatocytes. Their relationships with the endoplasmic reticulum observed in other species and in other organs were also demonstrable in this material. Some normal peroxisomes were found to display marginal plates or peripheral crystalline inclusions which were present in pathologic specimens as well. In certain inherited metabolic disorders (Menkes' steely hair disease, analbuminemia) the volume of the individual peroxisomes appeared to be considerably reduced. But most pathologic processes affecting hepatocytes seem to produce any or several of the following: increased volume or numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense inclusions, or clustering of peroxisomes in some portions of the cytoplasm. Some of these abnormalities are reversible based on observations in three patients with Wilson's disease treated with D-penicillamine. The mean +/- standard deviation of diameters of peroxisomes in four normal subjects was 0.618 +/- 0.143 mum. Significant reductions or increases in mean diameters of peroxisomes were noted in all but two of the 16 pathologic specimens. There were other morphologic abnormalities present in the remaining two specimens. We conclude that various pathologic processes involving the hepatocytic cytoplasm exert different effects on peroxisomes. Although no specific pattern of morphologic alteration emerged from this exploratory study, a possible involvement of peroxisomes ought to be considered whenever metabolic or pathologic processes affect the liver.",Biopsy;Endoplasmic Reticulum/ul [Ultrastructure];Humans;Inclusion Bodies/ul [Ultrastructure];*Liver/ul [Ultrastructure];Liver Diseases/pa [Pathology];*Microbodies/ul [Ultrastructure];*Organoids/ul [Ultrastructure],"Sternlieb, I.;Quintana, N.",1977,Feb,,0,0,
907,Penicillamine-induced arthropathy in Wilson's disease,,*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Joint Diseases/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Walshe, J. M.;Golding, D. N.",1977,,,0,0,
908,Preparation of and clinical experiences with trien for the treatment of Wilson's disease in absolute intolerance of D-penicillamine,,Adult;Drug Tolerance;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];*Trientine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);SJ76Y07H5F (Trientine),"Harders, H.;Cohnen, E.",1977,,,0,1,
909,Brief observations on the management of Wilson's disease,,Chelating Agents/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Pyridoxine/me [Metabolism];0 (Chelating Agents);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine),"Walshe, J. M.",1977,,,0,0,
910,[Wilson's disease. A case history],,Adolescent;*Affective Symptoms/et [Etiology];Age Factors;Ceruloplasmin/an [Analysis];*Child Behavior Disorders/et [Etiology];Copper/tu [Therapeutic Use];Diet Therapy;Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Potassium/tu [Therapeutic Use];*Psychotic Disorders/et [Etiology];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium),"Findlay, D.",1976,Mar,,0,0,
911,Platelet function and coagulation in patients with Wilson disease,"Sixteen patients with Wilson disease (hepatolenticular degeneration) were studied from the hemostatic point of view, particularly with regard to platelet function. Five of the patients had a mild bleeding tendency that was characterized by easy bruising. Moderate thrombocytopenia was observed in three of the five bleeders and in two of the others. One bleeder was thrombocytotic and hyperfibrinogenemic. Bleeding times, platelet retention and prothrombin consumption were abnormal rarely. However, 15 of the 16 patients had some abnormality of platelet aggregation: one when adenosine diphosphate was added to platelet rich plasma, three when epinephrine was added, and the remainder when collagen was added. The collagen abnormalities were delayed or absent aggregation (five patients, four of whom were bleeders) and absence of a change of shape (12 of the 16 patients). Platelet aggregation was completely normal in only one patient.",Adolescent;Adult;*Blood Coagulation;*Blood Platelets;Child;Female;Hemorrhage/et [Etiology];*Hepatolenticular Degeneration/bl [Blood];Humans;Male;Middle Aged;Penicillamine/pd [Pharmacology];Platelet Aggregation;Thrombocytopenia/et [Etiology];GNN1DV99GX (Penicillamine),"Owen, C. A., Jr.;Goldstein, N. P.;Bowie, J. W.",1976,Feb,,0,0,
912,Letter: The pregnant woman with Wilson's disease,,Female;Fetus/de [Drug Effects];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Maternal-Fetal Exchange;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];Pregnancy;*Pregnancy Complications/dt [Drug Therapy];GNN1DV99GX (Penicillamine),"Albukerk, J. N.",1976,Mar 18,,0,0,
913,Wilson's disease: a rare genetic disorder,,"Diagnosis, Differential;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/th [Therapy];*Hepatolenticular Degeneration;Humans;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Basner, N. H.",1976,Dec,,0,0,
914,My battle against Wilson's disease,,Adult;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Humans;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Francone, C. A.",1976,Feb,,0,0,
915,Wilson's disease (hepatolenticular degeneration),"Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism which usually affects young people. Excess copper accumulates in the tissues, primarily in the liver, brain, and cornea. This copper deposition results in a wide range of hepatic and neurological symptoms, and may produce psychiatric illness. Hepatic involvement often occurs in childhood, while neurological deficits generally are detected at a later age. The disease is inherited in an autosomal recessive fashion. Ocular findings are of particular importance because the corneal copper deposition, forming the Kayser-Fleischer ring,is the only pathognomonic sign of the disease. The structure of the ring and the presence of copper have been well established. An anterior capsular deposition of copper in the lens results in a characteristic sunflower cataract in some of these patients. Other ocular abnormalities have been described but are much less common. The pathogenesis of the disease and the basic genetic defect remain obscure. It is clear that there is excess copper in the tissues, but the mechanism of its deposition is unknown. It is in some way associated with a failure to synthesize the serum copper protein ceruloplasmin normally. Another theory suggests that an abnormal protein with a high affinity for copper may bind the metal in the tissues. The diagnosis may be suggested by the clinical manifestations and confirmed by the presence of a Kayser-Fleischer ring. In the absence of these findings biochemical determinations are necessary. The most important of these are the serum ceruloplasmin, the urinary copper, and the hepatic copper concentration on biopsy. Treatment consists in the administration of the copper chelating agent, penicillamine, and the avoidance of a high copper intake. This usually results in marked clinical improvement if irreversible tissue damage has not occurred. Maintenance therapy for life is necessary in order to continue the negative copper balance. The detection and prophylactic treatment of asymptomatic individuals with the disease is especially important. Seven cases of Wilson's disease have been presented in order to illustrate many of the features which have been discussed, with emphasis on the ocular findings.","Adolescent;Adult;Cataract/et [Etiology];Ceruloplasmin/bl [Blood];Copper/ur [Urine];Descemet Membrane;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/et [Etiology];*Hepatolenticular Degeneration;Humans;Male;Penicillamine/tu [Therapeutic Use];Pigments, Biological;0 (Pigments, Biological);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Herron, B. E.",1976,,,0,0,
916,[Hepatolemticular degeneration (Wison's disease): prolonged treatment with D-penicillamine in 3 cases],,Adolescent;Adult;Child;Drug Evaluation;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Balcells, A.;Cabrer, B.;Cano, J. F.;Coll, J.;Ingelmo, M.;Vivancos, J.",1976,Oct 31,,0,0,
917,[Wilson's disease treated with penicillamine (author's transl)],,Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Aksamija-Rizvic, B.",1976,Aug,,0,0,
918,Inborn errors of copper metabolism: kinky hair disease and hepatolenticular degeneration. Therapeutic approaches,,"Adolescent;Child;*Copper/me [Metabolism];Copper/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/dh [Diet Therapy];*Hepatolenticular Degeneration/th [Therapy];Humans;Male;Menkes Kinky Hair Syndrome/dt [Drug Therapy];*Metal Metabolism, Inborn Errors/th [Therapy];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Dekaban, A. S.",1976,Apr-Jun,,0,0,
919,Effects of anticopper therapy on hepatocellular mitochondria in patients with Wilson's disease: an ultrastructural and stereological study,"Liver biopsy specimens from 7 patients with Wilson's disease (hepatolenticular degeneration), obtained before and after 3 to 5 years of D-penicillamine therapy, were studied by electron microscopy and stereology. The characteristic mitochondrial abnormalities encountered in the hepatocytes of untreated patients were less pronounced or disappeared after treatment in 5 of the 7 patients. Simultaneously, relative mitochondrial volume, surface density of the external mitochondrial membranes, and the number of these profiles per unit area increased, whereas abnormal elevations SGOT and SGPT returned to normal levels.","Adolescent;Child;Copper/an [Analysis];*Copper/ai [Antagonists & Inhibitors];Hepatolenticular Degeneration/dh [Diet Therapy];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/an [Analysis];Liver/pa [Pathology];Liver Function Tests;*Mitochondria, Liver/de [Drug Effects];Mitochondria, Liver/ul [Ultrastructure];Penicillamine/tu [Therapeutic Use];Photogrammetry;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Sternlieb, I.;Feldmann, G.",1976,Sep,,0,0,
920,[Hepatolenticular degeneration: biochemical and therapeutic considerations],,Adrenal Cortex Hormones/tu [Therapeutic Use];Brain/pa [Pathology];Ceruloplasmin/me [Metabolism];Chelating Agents/tu [Therapeutic Use];Copper/me [Metabolism];Dimercaprol/tu [Therapeutic Use];Edetic Acid/tu [Therapeutic Use];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration;Humans;Kidney/pa [Pathology];Liver/pa [Pathology];Penicillamine/tu [Therapeutic Use];Potassium/tu [Therapeutic Use];Zinc/me [Metabolism];0 (Adrenal Cortex Hormones);0 (Chelating Agents);0CPP32S55X (Dimercaprol);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc);RWP5GA015D (Potassium),Anonymous,1976,Mar 31,,0,0,
921,"Diagnosis of zinc, copper, and manganese abnormalities in man",,Adolescent;Adult;Animals;Brain Diseases/di [Diagnosis];Brain Diseases/ge [Genetics];Child;Copper/df [Deficiency];Copper/po [Poisoning];*Copper;Deficiency Diseases/di [Diagnosis];Evaluation Studies as Topic;Growth Disorders/di [Diagnosis];Hair;Hepatolenticular Degeneration/di [Diagnosis];Humans;Infant;Manganese/df [Deficiency];*Manganese;Manganese Poisoning;*Poisoning/di [Diagnosis];Zinc/df [Deficiency];Zinc/po [Poisoning];*Zinc;42Z2K6ZL8P (Manganese);789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Burch, R. E.;Sullivan, J. F.",1976,Jul,,0,0,
922,Letter: D-penicillamine and haemolytic anaemia,,"*Anemia, Hemolytic/ci [Chemically Induced];Child;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Lyle, W. H.",1976,Feb 21,,0,0,
923,[Hepato-cerebral dystrophy in children],,Adolescent;Child;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Humans;Male;Penicillamine/tu [Therapeutic Use];Unithiol/tu [Therapeutic Use];4076-02-2 (Unithiol);GNN1DV99GX (Penicillamine),"Malyshev Iu, I.",1975,Dec,,0,0,
924,Letter: Treatment of Wilson's disease,,Copper/ur [Urine];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Metronidazole/tu [Therapeutic Use];Penicillamine/tu [Therapeutic Use];140QMO216E (Metronidazole);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Gibbs, K.;Walshe, J. M.",1975,Dec 20,,0,0,
925,The effect of long term treatment with penicillamine on the copper content in the liver in patients with Wilson's disease,"Determination of hepatic copper concentration is the most exact criterion in the diagnosis of Wilson's disease. In the course of penicillamine therapy the copper content in the liver decreases, but normal values are achieved only after five or more years of treatment. Normalisation of the hepatic cooper concentration lags distinctly behind the clinical state. Distinct improvement of clinical state is already reached after a half to one year of treatment. The correlation between hepatic copper concentration and the amount of copper's excreted in the urine is statistically significant before the starting of treatment and during administration of penicillamine as well. The urinary copper excretion is a good indirect and indicator of the copper concentration in the liver.",Adolescent;Adult;Ceruloplasmin/an [Analysis];*Copper/me [Metabolism];Copper/ur [Urine];Female;Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Male;*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Marecek, Z.;Heyrovsky, A.;Volek, V.",1975,Oct,,0,0,
926,Juvenile Wilson disease: histologic and functional studies during penicillamine therapy,"Because the long-term effects of penicillamine on hepatic morphology in Wilson disease are virtually unknown, seven patients with this disorder were studied two to seven years after the onset of drug treatment. All were without symptoms at follow-up. By comparison to initial biopsies (four patients), posttreatment specimens showed either considerable reduction in portal fibrosis (two patients) or no significant change (two patients); portal inflammation and necrosis were greatly diminished or absent in three. In none was there complete restitution of normal architecture. Three patients lacked initial biopsies. In these, portal cirrhosis, inflammation and necrosis, and fatty vacuolization of the hepatocytes were present three, five, and seven years after onset of therapy. Lipofuscin pigment was abundant in follow-up biopsies. The data demonstrate that morphologic improvement is achieved in some patients with Wilson disease receiving penicilliamine, but that this is not predicted by biochemical factors. Sequential biopsies are necessary to evaluate completely the extent of healing.",Adolescent;Adult;Cell Nucleus/pa [Pathology];Ceruloplasmin/bl [Blood];Connective Tissue/pa [Pathology];Copper/me [Metabolism];Fatty Liver/pa [Pathology];Female;Hepatitis;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Kupffer Cells/pa [Pathology];Lipofuscin/an [Analysis];Liver/pa [Pathology];Liver Diseases;Liver Glycogen/an [Analysis];Male;Necrosis;*Penicillamine/tu [Therapeutic Use];0 (Lipofuscin);0 (Liver Glycogen);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Grand, R. J.;Vawter, G. F.",1975,Dec,,0,0,
927,Penicillamine in prevention of symptomatic Wilson's disease: 8 year follow up in two sibs,,"Adolescent;Child;Child, Preschool;Follow-Up Studies;Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Tiwary, C. M.;Rennert, O. M.;Garnica, A.",1975,Feb,,0,0,
928,Lipolysosomes in human hepatocytes. Ultrastructural and cytochemical studies of patients with Wilson's disease,"Lipid droplets surrounded by a peripheral membrane closely apposed to an electron-dense layer and containing acid phosphatase activity, similar to the lipolysosomes in hamsters described by Nehemiah and Novikoff (J. Cell Biol. 59: 246a, 1973; Exp. Mol. Pathol. 21:398, 1974), were found in the hepatocytes of patients with Wilson's disease. These organelles account for 1 to 2 per cent of the observed lipid droplets at the stage of the disease when excess fat is present. The occurrence of lipolysosomes in a condition not known to be associated with an acid lipase deficiency suggests that lipolysosomes may represent a nonspecific, alternate route for the mobilization of excess lipid from hepatocytes.","Acid Phosphatase/me [Metabolism];Adolescent;Adult;Biopsy, Needle;Child;Child, Preschool;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/en [Enzymology];*Hepatolenticular Degeneration/pa [Pathology];Histocytochemistry;Humans;Lipids;Liver/en [Enzymology];*Liver/ul [Ultrastructure];Lysosomes/en [Enzymology];*Lysosomes/ul [Ultrastructure];Male;Microscopy, Electron;Mitochondria, Liver/ul [Ultrastructure];Penicillamine/tu [Therapeutic Use];0 (Lipids);EC 3-1-3-2 (Acid Phosphatase);GNN1DV99GX (Penicillamine)","Hayashi, H.;Sternlieb, I.",1975,Jul,,0,0,
929,Myasthenia syndrome during penicillamine treatment,,Adolescent;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Myasthenia Gravis/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Time Factors;GNN1DV99GX (Penicillamine),"Czlonkowska, A.",1975,Jun 28,,0,0,
930,"Copper toxicity, rats and Wilson's disease",,Animals;Brain/me [Metabolism];Ceruloplasmin/me [Metabolism];Copper/me [Metabolism];Copper/pd [Pharmacology];*Copper;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Penicillamine/tu [Therapeutic Use];Rats;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),Anonymous,1975,Feb,,0,0,
931,Letter: Uses and usefulness of penicillamine,,Drug Tolerance;Ethylenediamines/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];United States;United States Food and Drug Administration;0 (Ethylenediamines);GNN1DV99GX (Penicillamine),"Scheinberg, I. H.",1975,May 15,,0,0,
932,D-penicillamine induced Goodpasture's syndrome in Wilson's disease,"Fatal pulmonary hemorrhages and rapidly progressive glomerulonephritis occurred in three patients with Wilson's disease (hepatolenticular degeneration) who had been treated with penicillamine for 2 to 31/2 years. Light microscopic studies of the kidneys showed severe glomerulonephritis with crescent formation, and the lungs showed intraalveolar hemorrhages. Although the clinical and pathologic abnormalities were those of Goodpasture's syndrome, immunofluorescence microscopic studies in the one case tested showed an interrupted, rather than linear, fluorescence pattern.",Adult;*Anti-Glomerular Basement Membrane Disease/ci [Chemically Induced];Child;Female;Fluorescent Antibody Technique;Glomerulonephritis/di [Diagnosis];Glomerulonephritis/dt [Drug Therapy];Glomerulonephritis/et [Etiology];Hemoptysis/et [Etiology];Hemorrhage/et [Etiology];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lung/cy [Cytology];Lung Diseases/et [Etiology];Male;Microscopy;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Prednisone/tu [Therapeutic Use];GNN1DV99GX (Penicillamine);VB0R961HZT (Prednisone),"Sternlieb, I.;Bennett, B.;Scheinberg, I. H.",1975,May,,0,0,
933,The development of cirrhosis in Wilson's disease,,"Ceruloplasmin/df [Deficiency];Ceruloplasmin/se [Secretion];*Copper/me [Metabolism];Copper/ur [Urine];Cornea/pa [Pathology];Cytosol/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/pp [Physiopathology];Hepatolenticular Degeneration/th [Therapy];Humans;*Liver/me [Metabolism];Liver/pa [Pathology];Liver/ul [Ultrastructure];*Liver Cirrhosis/pp [Physiopathology];Lysosomes/me [Metabolism];Metallothionein/me [Metabolism];Mitochondria, Liver/ul [Ultrastructure];Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];Prognosis;Protein Binding;Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);9038-94-2 (Metallothionein);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Sternlieb, I.",1975,May,,0,0,
934,"Newer aspects of the roles of zinc, manganese, and copper in human nutrition",,"Adult;Anemia/me [Metabolism];Animals;Biological Transport;Connective Tissue/me [Metabolism];*Copper/me [Metabolism];Copper/po [Poisoning];Deficiency Diseases/me [Metabolism];Erythrocytes/me [Metabolism];Female;Hepatolenticular Degeneration/me [Metabolism];Humans;Infant, Newborn;Intestinal Absorption;Male;*Manganese/me [Metabolism];Manganese Poisoning;Metalloproteins/me [Metabolism];Mutation;*Nutritional Physiological Phenomena;Organ Specificity;Pregnancy;Wound Healing;*Zinc/me [Metabolism];Zinc/po [Poisoning];0 (Metalloproteins);42Z2K6ZL8P (Manganese);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Burch, R. E.;Hahn, H. K.;Sullivan, J. F.",1975,Apr,,0,0,
935,Trace elements--a selective survey,,Adult;Child;Chromium/me [Metabolism];Cobalt/me [Metabolism];Copper/me [Metabolism];Erythrocytes/me [Metabolism];Fluorine/me [Metabolism];Hepatolenticular Degeneration/me [Metabolism];Humans;Iodine/an [Analysis];Iodine/me [Metabolism];Iron/me [Metabolism];Magnesium/me [Metabolism];Microchemistry;Molybdenum/me [Metabolism];Nickel/me [Metabolism];Nutritional Physiological Phenomena;Protein Binding;Selenium/me [Metabolism];Silicon/me [Metabolism];Tin/me [Metabolism];Trace Elements/an [Analysis];*Trace Elements/me [Metabolism];Vanadium/me [Metabolism];Zinc/me [Metabolism];0 (Trace Elements);00J9J9XKDE (Vanadium);0R0008Q3JB (Chromium);284SYP0193 (Fluorine);3G0H8C9362 (Cobalt);7440-31-5 (Tin);789U1901C5 (Copper);7OV03QG267 (Nickel);81AH48963U (Molybdenum);9679TC07X4 (Iodine);E1UOL152H7 (Iron);H6241UJ22B (Selenium);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc);Z4152N8IUI (Silicon),"Reinhold, J. G.",1975,Apr,,0,0,
936,Hemolytic anemia of Wilson's disease,,"Adult;Anemia, Hemolytic/bl [Blood];Anemia, Hemolytic/dt [Drug Therapy];*Anemia, Hemolytic/et [Etiology];Anemia, Hemolytic/ur [Urine];Bilirubin/bl [Blood];Ceruloplasmin/an [Analysis];Copper/bl [Blood];Copper/me [Metabolism];Copper/se [Secretion];Copper/ur [Urine];Erythrocyte Count;Female;Hemoglobins/an [Analysis];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Liver/me [Metabolism];Liver/se [Secretion];Male;Penicillamine/tu [Therapeutic Use];Reticulocytes;0 (Hemoglobins);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin)","Iser, J. H.;Stevens, B. J.;Stening, G. F.;Hurley, T. H.;Smallwood, R. A.",1974,Aug,,0,0,
937,Dysarthria in Wilson's disease,,Adolescent;Adult;Ataxia/et [Etiology];Athetosis/et [Etiology];Chorea/et [Etiology];Evaluation Studies as Topic;Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Muscle Rigidity/et [Etiology];Neurologic Examination;Penicillamine/tu [Therapeutic Use];Prognosis;Spasm/et [Etiology];Speech Disorders/di [Diagnosis];Speech Disorders/dt [Drug Therapy];*Speech Disorders/et [Etiology];Tape Recording;Voice;GNN1DV99GX (Penicillamine),"Berry, W. R.;Darley, F. L.;Aronson, A. E.",1974,Jun,,0,0,
938,Evidence for a urate reabsorptive defect in patients with Wilson's disease,,Arginine/ur [Urine];Follow-Up Studies;Glomerular Filtration Rate;Glutamine/ur [Urine];Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/ur [Urine];Humans;Kidney/de [Drug Effects];Kidney/me [Metabolism];Penicillamine/tu [Therapeutic Use];Pyrazinamide/me [Metabolism];Pyrazinamide/pd [Pharmacology];Serine/ur [Urine];Time Factors;Uric Acid/bl [Blood];*Uric Acid/me [Metabolism];Uric Acid/ur [Urine];0RH81L854J (Glutamine);268B43MJ25 (Uric Acid);2KNI5N06TI (Pyrazinamide);452VLY9402 (Serine);94ZLA3W45F (Arginine);GNN1DV99GX (Penicillamine),"Wilson, D. M.;Goldstein, P.",1974,,,0,0,
939,Trade names or approved names. Part III. Special cases. Drugs for rare diseases,,"Costs and Cost Analysis;Drug Evaluation;Drug Evaluation, Preclinical;*Drug Industry;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];*Research;GNN1DV99GX (Penicillamine)","Lyle, W. H.",1974,Feb,,0,0,
940,Use of the 198Au liver scan in assessing the therapeutic effect of penicillamine in Wilson's disease,,Adolescent;Female;Gold Radioisotopes;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];*Penicillamine/tu [Therapeutic Use];*Radionuclide Imaging;0 (Gold Radioisotopes);GNN1DV99GX (Penicillamine),"Chajek, T.",1974,Jan,,0,0,
941,[Nature of course and rehabilitation in the clinical stage of Wilson's disease],,"Adolescent;Adult;Age Factors;Basal Ganglia Diseases/di [Diagnosis];Child;Child, Preschool;Diagnosis, Differential;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/rh [Rehabilitation];Humans;Liver Cirrhosis/di [Diagnosis];Male;Penicillamine/tu [Therapeutic Use];Remission, Spontaneous;Time Factors;GNN1DV99GX (Penicillamine)","Lossner, J.;Eichner, B.;Bachmann, H.;Biesold, D.;Gunther, K.",1974,Nov,,0,0,
942,Letter: Peptic ulceration and D-penicillamine,,"Arthritis, Rheumatoid/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Peptic Ulcer/ci [Chemically Induced];Peptic Ulcer Hemorrhage/ci [Chemically Induced];Recurrence;Stomach Ulcer/co [Complications];Time Factors;GNN1DV99GX (Penicillamine)","Lyle, W. H.",1974,Aug 03,,0,0,
943,Ophthalmologic and genetic aspects of Wilson's disease (hepatolenticular degeneration),,Adult;Biopsy;Ceruloplasmin/an [Analysis];Copper/bl [Blood];Eye Manifestations;Female;Finland;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/pa [Pathology];Male;Neurologic Manifestations;Pedigree;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Karma, A.",1973,,,0,0,
944,Renal urate excretion in patients with Wilson's disease,,"Arginine/ur [Urine];Depression, Chemical;Glomerular Filtration Rate;Glutamine/ur [Urine];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pp [Physiopathology];*Hepatolenticular Degeneration/ur [Urine];Humans;Inulin;Kidney Tubules, Proximal/pp [Physiopathology];Penicillamine/tu [Therapeutic Use];Pyrazinamide/pd [Pharmacology];Serine/ur [Urine];Uric Acid/bl [Blood];Uric Acid/me [Metabolism];*Uric Acid/ur [Urine];Valine/ur [Urine];0RH81L854J (Glutamine);268B43MJ25 (Uric Acid);2KNI5N06TI (Pyrazinamide);452VLY9402 (Serine);9005-80-5 (Inulin);94ZLA3W45F (Arginine);GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine)","Wilson, D. M.;Goldstein, N. P.",1973,Nov,,0,0,
945,Elastosis perforans serpiginosa during penicillamine therapy for Wilson disease,,Adult;Biopsy;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];*Skin Diseases/ci [Chemically Induced];Skin Diseases/pa [Pathology];GNN1DV99GX (Penicillamine),"Pass, F.;Goldfischer, S.;Sternlieb, I.;Scheinberg, I. H.",1973,Nov,,0,0,
946,[Hepatocerebral degeneration (Wilson's disease). Demonstration of the clinical picture and demonstration of own case],,Adolescent;Ceruloplasmin/an [Analysis];Copper/bl [Blood];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Rosenberger, K.",1973,Sep,,0,0,
947,Copper chelation in patients with Wilson's disease. A comparison of penicillamine and triethylene tetramine dihydrochloride,,Adolescent;Adult;Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];Copper/bl [Blood];Copper/ur [Urine];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Metabolic Clearance Rate;Penicillamine/ae [Adverse Effects];Penicillamine/pd [Pharmacology];*Penicillamine/tu [Therapeutic Use];Radioisotopes/bl [Blood];Radioisotopes/ur [Urine];0 (Chelating Agents);0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1973,Jul,,0,1,
948,Penicillamine-induced cupriuria in normal subjects and in patients with active liver disease,,"Administration, Oral;Adolescent;Adult;Age Factors;Aspartate Aminotransferases/bl [Blood];Bilirubin/bl [Blood];Ceruloplasmin/an [Analysis];Chemical and Drug Induced Liver Injury/ur [Urine];Chronic Disease;Copper/bl [Blood];*Copper/ur [Urine];Female;Hepatitis/ur [Urine];Hepatolenticular Degeneration/ur [Urine];Humans;Liver Cirrhosis/ur [Urine];Liver Diseases/bl [Blood];Liver Diseases/en [Enzymology];*Liver Diseases/ur [Urine];Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/pd [Pharmacology];Sex Factors;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 2-6-1-1 (Aspartate Aminotransferases);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin)","Lynch, R. E.;Lee, G. R.;Cartwright, G. E.",1973,Jan,,0,0,
949,Atomic absorption spectrometry of trace metals in clinical pathology,,"Brain Diseases/me [Metabolism];Chromium/an [Analysis];Copper/an [Analysis];Copper/me [Metabolism];Copper/po [Poisoning];Deficiency Diseases/me [Metabolism];Growth Disorders/me [Metabolism];Hair/an [Analysis];Hepatolenticular Degeneration/me [Metabolism];Hodgkin Disease/me [Metabolism];Humans;Intellectual Disability/me [Metabolism];Iron/an [Analysis];Lead/an [Analysis];Methods;Nails/an [Analysis];Nickel/an [Analysis];Poisoning/me [Metabolism];*Spectrophotometry, Atomic/is [Instrumentation];Syndrome;*Trace Elements/an [Analysis];Zinc/an [Analysis];0 (Trace Elements);0R0008Q3JB (Chromium);2P299V784P (Lead);789U1901C5 (Copper);7OV03QG267 (Nickel);E1UOL152H7 (Iron);J41CSQ7QDS (Zinc)","Sunderman, F. W., Jr.",1973,Dec,,0,0,
950,Diagnosis of allergic drug reaction,,"Antibodies, Antinuclear;Antibody Formation;Antigen-Antibody Complex;Coombs Test;Dextrans;*Drug Hypersensitivity/di [Diagnosis];Erythrocytes/im [Immunology];Fluorescent Antibody Technique;Glomerulonephritis/co [Complications];Glomerulonephritis/im [Immunology];Hemagglutination Tests;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Imidazoles;Male;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Proteinuria/et [Etiology];0 (Antibodies, Antinuclear);0 (Antigen-Antibody Complex);0 (Dextrans);0 (Imidazoles);GNN1DV99GX (Penicillamine)","Amos, H. E.",1973,,,0,0,
951,[Diagnostic and therapeutic aspects of Wilson's disease in the preclinical stage],,"Adult;Ceruloplasmin/an [Analysis];Child;Child, Preschool;Copper/bl [Blood];Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Long-Term Care;Male;Penicillamine/ad [Administration & Dosage];*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Lobbner, J.;Bachmann, H.;Eichner, B.;Biesold, D.;Gunther, K.",1973,May,,0,0,
952,Wilson's disease in the United Kingdom and Taiwan. I. General characteristics of 142 cases and prognosis. II. A genetic analysis of 88 cases,,Adolescent;Adult;Age Factors;Child;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/mo [Mortality];*Hepatolenticular Degeneration;Humans;Long-Term Care;Male;Middle Aged;Pedigree;Penicillamine/tu [Therapeutic Use];Prognosis;Sex Factors;Taiwan;United Kingdom;GNN1DV99GX (Penicillamine),"Strickland, G. T.;Frommer, D.;Leu, M. L.;Pollard, R.;Sherlock, S.;Cumings, J. N.",1973,Jul,,1,1,
953,'Torsion dystony' and abnormal copper metabolism,,"Adult;Ceruloplasmin/an [Analysis];*Copper/me [Metabolism];Copper/ur [Urine];Diagnosis, Differential;Diazepam/tu [Therapeutic Use];Dihydroxyphenylalanine/tu [Therapeutic Use];Dystonia Musculorum Deformans/di [Diagnosis];Dystonia Musculorum Deformans/dt [Drug Therapy];Dystonia Musculorum Deformans/et [Etiology];Dystonia Musculorum Deformans/ge [Genetics];*Dystonia Musculorum Deformans/me [Metabolism];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/et [Etiology];Humans;Liver/me [Metabolism];Male;*Metal Metabolism, Inborn Errors/co [Complications];Pedigree;Penicillamine/tu [Therapeutic Use];Torsion Abnormality/et [Etiology];63-84-3 (Dihydroxyphenylalanine);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);Q3JTX2Q7TU (Diazepam)","Herishanu, Y.;Loewinger, E.",1972,,,0,0,
954,Osteoarticular changes in Wilson's disease,,"Adolescent;Adult;Bone and Bones/an [Analysis];Calcinosis/dg [Diagnostic Imaging];*Calcinosis/et [Etiology];Carpal Bones/dg [Diagnostic Imaging];Child;Child, Preschool;Chondrocalcinosis/et [Etiology];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dg [Diagnostic Imaging];Humans;*Joint Diseases/et [Etiology];Knee/dg [Diagnostic Imaging];Knee Joint;Male;Minerals/an [Analysis];Osteoarthritis/dg [Diagnostic Imaging];*Osteoarthritis/et [Etiology];Patella;Penicillamine/tu [Therapeutic Use];Radiography;Wrist Joint;0 (Minerals);GNN1DV99GX (Penicillamine)","Feller, E. R.;Schumacher, H. R.",1972,May-Jun,,0,0,
955,Chronic hepatitis as a first manifestation of Wilson's disease,,Adolescent;Adult;Biopsy;Ceruloplasmin/bl [Blood];Ceruloplasmin/ur [Urine];Child;Chronic Disease;Copper/an [Analysis];Copper/ur [Urine];Eye Manifestations;Female;*Hepatitis/di [Diagnosis];Hepatitis/pa [Pathology];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/an [Analysis];Liver/pa [Pathology];Male;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Sternlieb, I.;Scheinberg, I. H.",1972,Jan,,0,0,
956,Glucose intolerance in Wilson's disease. Normalization after treatment with penicillamine,,Adolescent;Biopsy;*Blood Glucose/me [Metabolism];Copper/bl [Blood];Female;Glucose Tolerance Test;Growth Hormone/bl [Blood];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration;Humans;Insulin/bl [Blood];Male;*Penicillamine/tu [Therapeutic Use];0 (Blood Glucose);0 (Insulin);789U1901C5 (Copper);9002-72-6 (Growth Hormone);GNN1DV99GX (Penicillamine),"Johansen, K.;Gregersen, G.",1972,Apr,,0,0,
957,Renal abnormalities in heterozygotes for Wilson's disease: genes or copper?,,Ceruloplasmin/an [Analysis];Copper/bl [Blood];*Copper/me [Metabolism];Copper/ur [Urine];Genes;Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/ge [Genetics];*Heterozygote;Humans;*Kidney/ab [Abnormalities];Kidney/me [Metabolism];Kidney/pp [Physiopathology];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Strickland, G. T.;Leu, M. L.",1972,Aug,,0,0,
958,Febrile penicillamine eruption,,Antigen-Antibody Complex;Asian Continental Ancestry Group;*Drug Eruptions;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];Protein Binding;0 (Antigen-Antibody Complex);GNN1DV99GX (Penicillamine),"Strickland, G. T.",1972,May,,0,0,
959,Polymyositis and penicillamine,,"Adult;Autoimmune Diseases;Diagnosis, Differential;Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/im [Immunology];Homozygote;Humans;Lupus Erythematosus, Systemic/im [Immunology];Muscles/pa [Pathology];*Myositis/ci [Chemically Induced];Myositis/di [Diagnosis];Myositis/im [Immunology];Myositis/pa [Pathology];Neutrophils;Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine)","Schraeder, P. L.;Peters, H. A.;Dahl, D. S.",1972,Nov,,0,0,
960,Metabolic studies in Wilson's disease. Evaluation of efficacy of chelation therapy in respect to copper balance,,Adolescent;Adult;Chelating Agents/tu [Therapeutic Use];Child;*Copper/me [Metabolism];Copper/ur [Urine];Diet Therapy;Evaluation Studies as Topic;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Penicillamine/tu [Therapeutic Use];Pentetic Acid/tu [Therapeutic Use];Potassium/tu [Therapeutic Use];Time Factors;0 (Chelating Agents);789U1901C5 (Copper);7A314HQM0I (Pentetic Acid);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium),"Strickland, G. T.;Blackwell, R. Q.;Watten, R. H.",1971,Jul,,0,1,
961,Wilson's disease (hepatolenticular degeneration). Treatment with penicillamine and changes in hepatic trapping of radioactive copper,,"Adolescent;Adult;Child;Child, Preschool;*Copper/me [Metabolism];Diet Therapy;Dimercaprol/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Male;Middle Aged;Penicillamine/ad [Administration & Dosage];Radioisotopes;0 (Radioisotopes);0CPP32S55X (Dimercaprol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Goldstein, N. P.;Tauxe, W. N.;McCall, J. T.;Randall, R. V.;Gross, J. B.",1971,May,,0,0,
962,"Tissue copper, zinc, and manganese levels in Wilson's disease: studies with the use of neutron activation analysis",,*Activation Analysis;Adolescent;Adrenal Glands/an [Analysis];Adult;Autopsy;Brain Chemistry;Ceruloplasmin/an [Analysis];*Copper/an [Analysis];Copper/ur [Urine];Diaphragm/an [Analysis];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Kidney/an [Analysis];Liver/an [Analysis];Liver Function Tests;Lung/an [Analysis];Male;*Manganese/an [Analysis];Muscles/an [Analysis];Pancreas/an [Analysis];Penicillamine/tu [Therapeutic Use];Spinal Cord/an [Analysis];Spleen/an [Analysis];Stomach/an [Analysis];*Zinc/an [Analysis];42Z2K6ZL8P (Manganese);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"Yeh, S. J.;Leu, M. L.;Strickland, G. T.",1971,Mar,,0,0,
963,The varied manifestations of Wilson's disease,,"Adolescent;Anemia, Hemolytic/et [Etiology];Ascites/co [Complications];Ceruloplasmin/an [Analysis];Child;Copper/bl [Blood];Copper/ur [Urine];Diseases in Twins;Eye Manifestations;Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/th [Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Hypertension, Portal/co [Complications];Jaundice/co [Complications];Liver Cirrhosis/co [Complications];Liver Function Tests;Male;Neurologic Manifestations;Osteoporosis/et [Etiology];Penicillamine/tu [Therapeutic Use];Splenomegaly/co [Complications];Tremor/co [Complications];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Slovis, T. L.;Dubois, R. S.;Rodgerson, D. O.;Silverman, A.",1971,Apr,,0,0,
964,Wilson's disease with reversible renal tubular dysfunction. Correlation with proximal tubular ultrastructure,,"*Acute Kidney Injury/co [Complications];Acute Kidney Injury/pa [Pathology];Adolescent;Antibodies, Antinuclear/an [Analysis];Biopsy;Copper/me [Metabolism];Copper/ur [Urine];Creatinine/ur [Urine];Female;Glomerular Filtration Rate;Glomerulonephritis/ci [Chemically Induced];Glomerulonephritis/pa [Pathology];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Kidney Glomerulus/pa [Pathology];*Kidney Tubules/pa [Pathology];Lupus Erythematosus, Systemic/ci [Chemically Induced];Microscopy, Electron;Penicillamine/ad [Administration & Dosage];*Penicillamine/ae [Adverse Effects];Proteinuria;0 (Antibodies, Antinuclear);789U1901C5 (Copper);AYI8EX34EU (Creatinine);GNN1DV99GX (Penicillamine)","Elsas, L. J.;Hayslett, J. P.;Spargo, B. H.;Durant, J. L.;Rosenberg, L. E.",1971,Sep,,0,0,
965,Renal clearances of different amino acids in Wilson's disease before and after treatment with penicillamine,,Adolescent;Albuminuria;*Amino Acids/me [Metabolism];Aminohippuric Acids;Copper/ur [Urine];Female;Glomerular Filtration Rate;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Inulin;Kidney Function Tests;Kidney Glomerulus/de [Drug Effects];Kidney Glomerulus/pp [Physiopathology];Kidney Tubules/de [Drug Effects];*Kidney Tubules/pp [Physiopathology];Male;*Penicillamine/tu [Therapeutic Use];Phosphates/me [Metabolism];Uric Acid/ur [Urine];0 (Amino Acids);0 (Aminohippuric Acids);0 (Phosphates);268B43MJ25 (Uric Acid);789U1901C5 (Copper);9005-80-5 (Inulin);GNN1DV99GX (Penicillamine),"Schonheyder, F.;Gregersen, G.;Hansen, H. E.;Skov, P. E.",1971,Nov,,0,0,
966,Studies with 35S-labelled DL-penicillamine in patients with Wilson's disease,,"Administration, Oral;Adolescent;Adult;Autoradiography;Blood Protein Electrophoresis;Body Fluids/an [Analysis];Chromatography, Paper;Female;Filtration;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Intestinal Absorption;Kidney/me [Metabolism];Male;Penicillamine/ad [Administration & Dosage];Penicillamine/bl [Blood];*Penicillamine/me [Metabolism];Penicillamine/ur [Urine];Protein Binding;Serum Albumin;Sulfur Isotopes;0 (Serum Albumin);0 (Sulfur Isotopes);GNN1DV99GX (Penicillamine)","Gibbs, K.;Walshe, J. M.",1971,Apr,,0,0,
967,The binding of copper by bile and serum,,Adolescent;Adult;Animals;*Bile/an [Analysis];Bile Acids and Salts;Child;*Copper/an [Analysis];*Copper/bl [Blood];Copper/me [Metabolism];Dialysis;Edetic Acid;Female;Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Penicillamine;*Protein Binding;Radioisotopes;Rats;Serum Albumin;Sodium Chloride;0 (Bile Acids and Salts);0 (Radioisotopes);0 (Serum Albumin);451W47IQ8X (Sodium Chloride);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine),"Frommer, D.",1971,Dec,,0,0,
968,Long-term therapy of Wilson's disease,,Adolescent;Adult;Blood Cell Count;Central Nervous System/pp [Physiopathology];Child;Copper/me [Metabolism];Cornea/pp [Physiopathology];Female;Follow-Up Studies;*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/et [Etiology];Hepatolenticular Degeneration/pp [Physiopathology];Humans;Kidney/pp [Physiopathology];Liver/pp [Physiopathology];Long-Term Care;Male;*Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];Pigmentation;*Potassium/ad [Administration & Dosage];Potassium/ae [Adverse Effects];*Sulfides/ad [Administration & Dosage];Sulfides/ae [Adverse Effects];0 (Sulfides);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium),"Deiss, A.;Lynch, R. E.;Lee, G. R.;Cartwright, G. E.",1971,Jul,,0,1,
969,Penicillamine and analogous chelating agents,,Acetates/pd [Pharmacology];Acetates/tu [Therapeutic Use];Acetates/to [Toxicity];Amino Acid Oxidoreductases;Animals;Chelating Agents;Copper/ur [Urine];Cysteine/pd [Pharmacology];Cysteine/tu [Therapeutic Use];*Cysteine;D-Amino-Acid Oxidase;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ur [Urine];Humans;Lethal Dose 50;Liver/en [Enzymology];Lyases;Mercury Poisoning/pc [Prevention & Control];Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Penicillamine/to [Toxicity];*Penicillamine;Rats;Species Specificity;Stereoisomerism;Venoms;0 (Acetates);0 (Chelating Agents);0 (Venoms);789U1901C5 (Copper);EC 1-4 (Amino Acid Oxidoreductases);EC 1-4-3-3 (D-Amino-Acid Oxidase);EC 4 (Lyases);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Aposhian, H. V.",1971,Jul 06,,0,1,
970,Chelating agents in medicine,,"Chelating Agents/tu [Therapeutic Use];*Chelating Agents;Chemistry, Pharmaceutical;Deferoxamine;Dicumarol;Edetic Acid;Hemochromatosis/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lead Poisoning/dt [Drug Therapy];Penicillamine;0 (Chelating Agents);7QID3E7BG7 (Dicumarol);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine);J06Y7MXW4D (Deferoxamine)",Anonymous,1971,May 01,,0,0,
971,"Inborn errors of metabolism in neurology (Wilson's disease, Refsum's disease and lipidoses)",,"Adolescent;Adult;Cerebral Cortex/an [Analysis];Ceruloplasmin;Cholesterol/an [Analysis];Copper/bl [Blood];Copper/me [Metabolism];Copper/ur [Urine];Dimercaprol/tu [Therapeutic Use];Fatty Acids/an [Analysis];Fatty Acids/bl [Blood];Fatty Acids/cf [Cerebrospinal Fluid];Fatty Acids/me [Metabolism];Female;Gangliosides/me [Metabolism];Hepatolenticular Degeneration/en [Enzymology];*Hepatolenticular Degeneration/me [Metabolism];Humans;Kidney/an [Analysis];Lipidoses/en [Enzymology];*Lipidoses/me [Metabolism];Liver/an [Analysis];Male;Metabolism, Inborn Errors;Mixed Function Oxygenases/me [Metabolism];Myocardium/an [Analysis];*Nervous System Diseases/me [Metabolism];Optic Nerve/an [Analysis];Penicillamine/tu [Therapeutic Use];Peripheral Nerves/an [Analysis];*Refsum Disease/me [Metabolism];Spleen/an [Analysis];0 (Fatty Acids);0 (Gangliosides);0CPP32S55X (Dimercaprol);789U1901C5 (Copper);97C5T2UQ7J (Cholesterol);EC 1 (Mixed Function Oxygenases);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Cumings, J. N.",1971,Mar,,0,0,
972,Effect of DDT on the nursing neonate,,"Animals;*Animals, Newborn/gd [Growth & Development];Body Weight;Breast Feeding;Calcium/an [Analysis];*Calcium/me [Metabolism];Copper/an [Analysis];*Copper/me [Metabolism];*DDT/pd [Pharmacology];DDT/to [Toxicity];Female;Food Contamination;Hepatolenticular Degeneration/me [Metabolism];Humans;Infant, Newborn;Iron/an [Analysis];*Iron/me [Metabolism];Liver/an [Analysis];*Liver/me [Metabolism];Magnesium/an [Analysis];*Magnesium/me [Metabolism];Manganese/an [Analysis];*Manganese/me [Metabolism];Maternal-Fetal Exchange;Mortality;Potassium/an [Analysis];*Potassium/me [Metabolism];Pregnancy;Rats;Spectrophotometry;Zinc/an [Analysis];*Zinc/me [Metabolism];42Z2K6ZL8P (Manganese);789U1901C5 (Copper);Ciw5s16655 (ddt);E1UOL152H7 (Iron);I38ZP9992A (Magnesium);J41CSQ7QDS (Zinc);RWP5GA015D (Potassium);SY7Q814VUP (Calcium)","Fahim, M. S.;Bennett, R.;Hall, D. G.",1970,Dec 19,,0,0,
973,Prevention of Wilson's disease--a long term follow-up,,"Adolescent;Adult;Child;Child, Preschool;Copper/me [Metabolism];*Diet Therapy;Female;Follow-Up Studies;Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;*Penicillamine/ad [Administration & Dosage];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Arima, M.;Komiya, K.",1970,Dec,,0,0,
974,Renal function in Wilson's disease: response to penicillamine therapy,,Adolescent;Adult;Aminohippuric Acids;Ammonium Chloride;Calcium/ur [Urine];Dehydration;Female;Follow-Up Studies;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Hypergammaglobulinemia;Immunoglobulin G/an [Analysis];Inulin;*Kidney/pp [Physiopathology];Kidney Concentrating Ability;Kidney Function Tests;Liver Cirrhosis/pp [Physiopathology];Male;Middle Aged;Natriuresis;*Penicillamine/tu [Therapeutic Use];Phosphorus/ur [Urine];Potassium/ur [Urine];Proteinuria;Renal Aminoacidurias;Uric Acid/ur [Urine];0 (Aminohippuric Acids);0 (Immunoglobulin G);01Q9PC255D (Ammonium Chloride);268B43MJ25 (Uric Acid);27YLU75U4W (Phosphorus);9005-80-5 (Inulin);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium);SY7Q814VUP (Calcium),"Leu, M. L.;Strickland, G. T.;Gutman, R. A.",1970,Dec,,0,0,
975,Heptolenticular degeneration (Wilson's disease) in an Australian Aboriginal,,Adult;Australia;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration;Humans;Male;Mutation;Oceanic Ancestry Group;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Gollan, J. L.;Hicks, E. P.;Gordo, J. V.",1970,Dec 19,,0,0,
976,"Muscle copper, zinc, and manganese levels in Wilson's disease: studies with the use of neutron-activation analysis",,*Activation Analysis;Adolescent;Adult;Biopsy;Child;*Copper/an [Analysis];Female;Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Manganese/an [Analysis];*Muscles/an [Analysis];*Zinc/an [Analysis];42Z2K6ZL8P (Manganese);789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Leu, M. L.;Strickland, G. T.;Beckner, W. M.;Chen, T. S.;Wang, C. C.;Yeh, S. J.",1970,Sep,,0,0,
977,Hemolytic anemia in Wilson's disease,,"Adult;*Anemia, Hemolytic/et [Etiology];*Copper/bl [Blood];Copper/me [Metabolism];Copper/pd [Pharmacology];Copper/ur [Urine];Erythrocytes/en [Enzymology];*Erythrocytes/me [Metabolism];Female;Glucosephosphate Dehydrogenase/bl [Blood];Glutathione/bl [Blood];Glutathione Reductase/bl [Blood];Heinz Bodies;Hemolysis/de [Drug Effects];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Phenylhydrazines;Pregnancy;0 (Phenylhydrazines);789U1901C5 (Copper);EC 1-1-1-49 (Glucosephosphate Dehydrogenase);EC 1-8-1-7 (Glutathione Reductase);GAN16C9B8O (Glutathione);GNN1DV99GX (Penicillamine)","Deiss, A.;Lee, G. R.;Cartwright, G. E.",1970,Sep,,0,0,
978,Essential micronutrient elements. Biochemistry and changes in liver disorders,,Alcohol Oxidoreductases/me [Metabolism];Cadmium/me [Metabolism];Copper/me [Metabolism];Hair/me [Metabolism];Hepatolenticular Degeneration/me [Metabolism];Humans;Iron/me [Metabolism];Liver Cirrhosis;*Liver Diseases/me [Metabolism];Manganese/me [Metabolism];Molybdenum/me [Metabolism];Selenium/me [Metabolism];*Trace Elements/me [Metabolism];Zinc/bl [Blood];Zinc/me [Metabolism];Zinc/ur [Urine];0 (Trace Elements);00BH33GNGH (Cadmium);42Z2K6ZL8P (Manganese);789U1901C5 (Copper);81AH48963U (Molybdenum);E1UOL152H7 (Iron);EC 1-1 (Alcohol Oxidoreductases);H6241UJ22B (Selenium);J41CSQ7QDS (Zinc),"Prasad, A. S.;Oberleas, D.;Rajasekaran, G.",1970,May,,0,0,
979,Hepatolenticular degeneration (Wilson's disease),,Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),Anonymous,1970,Mar,,0,0,
980,"Penicillamine-induced normalization of clinical signs, and liver morphology and histochemistry in a case of Wilson's disease",,Ceruloplasmin/bl [Blood];Child;*Copper/me [Metabolism];Copper/ur [Urine];Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];Histocytochemistry;Humans;Liver/me [Metabolism];*Liver/pa [Pathology];Liver Cirrhosis/dt [Drug Therapy];Liver Cirrhosis/pa [Pathology];*Penicillamine/tu [Therapeutic Use];Radioimmunoassay;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Falkmer, S.;Samuelson, G.;Sjolin, S.",1970,Feb,,0,0,
981,Effect of treatment on renal function in severe osteomalacia due to Wilson's disease,"A patient with Wilson's disease presented at the age of 41 with a neurological defect and gross osteomalacia secondary to a defect of renal tubular reabsorption. He also showed the unusual features of a renal stone in the presence of the Fanconi syndrome and a relatively low alkaline phosphatase level, possibly due to the additional inherited defect of hypophosphatasia. During four years of treatment with penicillamine and calciferol clinical improvement was spectacular. Details of amino-acid clearances before and after treatment are given, and the results suggest that, as in the brain and the liver, the function of the distal renal tubules may be restored in Wilson's disease when copper is removed.",Adult;Alkaline Phosphatase/bl [Blood];Amino Acids/bl [Blood];Amino Acids/me [Metabolism];Amino Acids/ur [Urine];Ergocalciferols/tu [Therapeutic Use];Fanconi Syndrome/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Hypophosphatasia/ge [Genetics];*Kidney/pp [Physiopathology];Kidney Calculi/co [Complications];Male;Metabolic Clearance Rate;Neurologic Manifestations;Osteomalacia/et [Etiology];*Osteomalacia/pp [Physiopathology];Penicillamine/tu [Therapeutic Use];*Sex Chromosome Aberrations;0 (Amino Acids);0 (Ergocalciferols);EC 3-1-3-1 (Alkaline Phosphatase);GNN1DV99GX (Penicillamine),"Monro, P.",1970,Sep,,0,0,
982,Continuing the copper saga,,Adult;Animals;Brain Diseases/ci [Chemically Induced];*Copper/to [Toxicity];*Diet;Female;Gastrointestinal Diseases/ci [Chemically Induced];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/tu [Therapeutic Use];Proteins/me [Metabolism];Sheep;Swine;0 (Proteins);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),Anonymous,1970,Aug,,0,0,
983,Ineffectiveness of L-dopa as supplement to penicillamine in a case of Wilson's disease,,Adult;Carbon Isotopes;Dihydroxyphenylalanine/bl [Blood];*Dihydroxyphenylalanine/tu [Therapeutic Use];Dihydroxyphenylalanine/ur [Urine];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];Spectrophotometry;0 (Carbon Isotopes);63-84-3 (Dihydroxyphenylalanine);GNN1DV99GX (Penicillamine),"Morgan, J. P.;Preziosi, T. J.;Bianchine, J. R.",1970,Sep 26,,0,0,
984,Triethylene tetramine,,Animals;Ethylenediamines/ae [Adverse Effects];*Ethylenediamines/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Rats;0 (Ethylenediamines),"Walshe, J. M.",1970,Jul 18,,0,0,
985,Treatment of Wilson's disease with L-dopa after failure with penicillamine,,Adolescent;Carboxy-Lyases/ai [Antagonists & Inhibitors];Dihydroxyphenylalanine/ad [Administration & Dosage];*Dihydroxyphenylalanine/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];63-84-3 (Dihydroxyphenylalanine);EC 4-1-1 (Carboxy-Lyases);GNN1DV99GX (Penicillamine),"Barbeau, A.;Friesen, H.",1970,May 30,,0,0,
986,Bleeding oesophageal varices in patients with Wilson's disease,,"Adolescent;Adult;Azygos Vein/su [Surgery];Child;Esophageal Diseases/co [Complications];*Esophageal and Gastric Varices/co [Complications];Esophageal and Gastric Varices/mo [Mortality];Esophageal and Gastric Varices/su [Surgery];Female;Gastrointestinal Hemorrhage/co [Complications];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];Portacaval Shunt, Surgical;Portal Vein/su [Surgery];Prognosis;Splenectomy;Stomach/su [Surgery];GNN1DV99GX (Penicillamine)","Sternlieb, I.;Scheinberg, I. H.;Walshe, J. M.",1970,Mar 28,,0,0,
987,Coagulation abnormalities in Wilson's disease,,"Adolescent;*Blood Coagulation Disorders/co [Complications];Blood Platelets/de [Drug Effects];Child;Child, Preschool;Female;Fibrinolysis/de [Drug Effects];*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine)","Fischer, M.;Hayek, H.;Schnack, H.;Schenck, W.;Bauer, B.;Kunzer, W.",1969,May,,0,0,
988,"Gastrointestinal absorption of copper: studies with 64Cu, 95Zr, a whole-body counter and the scintillation camera",,"Adolescent;Adult;Aged;Copper/bl [Blood];*Copper/me [Metabolism];Copper/ur [Urine];Duodenum/me [Metabolism];Feces;Female;*Hepatolenticular Degeneration/me [Metabolism];Humans;Injections, Intravenous;Intestinal Absorption/de [Drug Effects];*Intestinal Absorption;Male;Middle Aged;Penicillamine/pd [Pharmacology];Radioisotopes/ad [Administration & Dosage];Radionuclide Imaging;Stomach/me [Metabolism];Time Factors;*Zirconium;0 (Radioisotopes);789U1901C5 (Copper);C6V6S92N3C (Zirconium);GNN1DV99GX (Penicillamine)","Weber, P. M.;O'Reilly, S.;Pollycove, M.;Shipley, L.",1969,Sep,,0,0,
989,"""Sunflower cataract"" in Wilson's disease",,"*Cataract/et [Etiology];Child;Copper/me [Metabolism];Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Lens, Crystalline/me [Metabolism];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Cairns, J. E.;Williams, H. P.;Walshe, J. M.",1969,Jul 12,,0,0,
990,Wilson's disease,,Adolescent;Adult;Animals;Brain/de [Drug Effects];Child;Columbidae;Copper/me [Metabolism];Copper/pd [Pharmacology];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration;Humans;In Vitro Techniques;Liver/me [Metabolism];Penicillamine/tu [Therapeutic Use];Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1969,Feb,,0,0,375
991,Treatment of Wilson's disease (hepatolenticular degeneration) with penicillamine and low-copper diet,,Copper/me [Metabolism];Diet Therapy;Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];*Hepatolenticular Degeneration/th [Therapy];Humans;Penicillamine/ad [Administration & Dosage];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Goldstein, N. P.;Tauxe, W. N.;McCall, J. T.;Gross, J. B.;Randall, R. V.",1969,,,0,0,
992,Studies with radioactive copper (64Cu and 67Cu): abdominal scintiscans in patients with Wilson's disease,,Adolescent;Adult;*Copper;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Penicillamine/tu [Therapeutic Use];Radioisotopes;*Radionuclide Imaging;0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Osborn, S. B.;Szaz, K. F.;Walshe, J. M.",1969,Oct,,0,0,
993,Disappearance of Kayser-Fleischer rings. Effects of penicillamine,,Adult;Color;Cornea/pa [Pathology];Descemet Membrane/pa [Pathology];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];Photography;GNN1DV99GX (Penicillamine),"Sussman, W.;Scheinberg, I. H.",1969,Dec,,0,0,
994,Interruption of the tryptophan-nicotinic acid pathway by penicillamine-induced pyridoxine deficiency in patients with Wilson's disease and in experimental animals,,Animals;Carbon Isotopes;Chromatography;Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/ur [Urine];Humans;Kynurenine/me [Metabolism];Male;*Nicotinic Acids/me [Metabolism];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Rats;*Tryptophan/me [Metabolism];Urine/an [Analysis];Vitamin B 6 Deficiency/ci [Chemically Induced];*Vitamin B 6 Deficiency/me [Metabolism];Xanthurenates/me [Metabolism];Xanthurenates/ur [Urine];ortho-Aminobenzoates/me [Metabolism];0 (Carbon Isotopes);0 (Nicotinic Acids);0 (Xanthurenates);0 (ortho-Aminobenzoates);343-65-7 (Kynurenine);8DUH1N11BX (Tryptophan);GNN1DV99GX (Penicillamine),"Gibbs, K.;Walshe, J. M.",1969,Sep 30,,0,0,
995,Wilson's disease: the role of penicillamine,,Copper/me [Metabolism];Diet Therapy;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Carmichael, B. M.",1969,Oct,,0,0,
996,Treatment of hepatolenticular degeneration. (Wilson's disease),,"Acute Disease;Ceruloplasmin/bl [Blood];Copper/bl [Blood];Copper/ur [Urine];Diet Therapy;Dimercaprol/ad [Administration & Dosage];Edetic Acid/ad [Administration & Dosage];Ethinyl Estradiol/ad [Administration & Dosage];Hepatolenticular Degeneration/bl [Blood];*Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/th [Therapy];Humans;Injections, Intravenous;Ion Exchange Resins/tu [Therapeutic Use];Penicillamine/ad [Administration & Dosage];Potassium/tu [Therapeutic Use];Prognosis;Sulfides/tu [Therapeutic Use];Tropanes/tu [Therapeutic Use];0 (Ion Exchange Resins);0 (Sulfides);0 (Tropanes);0CPP32S55X (Dimercaprol);423D2T571U (Ethinyl Estradiol);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium)","Spellberg, M. A.",1969,Aug,,0,0,
997,A mechanism for the action of penicillamine in the treatment of Wilson's disease,,"Chelating Agents/pd [Pharmacology];*Copper;Cysteine/pd [Pharmacology];Edetic Acid/pd [Pharmacology];Electron Spin Resonance Spectroscopy;*Hepatolenticular Degeneration/dt [Drug Therapy];Methods;Models, Biological;Nitrogen;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Sulfur;Thiosemicarbazones/pd [Pharmacology];0 (Chelating Agents);0 (Thiosemicarbazones);70FD1KFU70 (Sulfur);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine);N762921K75 (Nitrogen)","Peisach, J.;Blumberg, W. E.",1969,Mar,,0,0,
998,Management of penicillamine nephropathy in Wilson's disease: a new chelating agent,,Adolescent;*Chelating Agents/tu [Therapeutic Use];Chlorides;Copper/me [Metabolism];*Ethylenediamines/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Nephrotic Syndrome/ci [Chemically Induced];Neurologic Manifestations;*Penicillamine/ae [Adverse Effects];0 (Chelating Agents);0 (Chlorides);0 (Ethylenediamines);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1969,Dec 27,,0,0,
999,Uncommon EEG findings in hepato-lenticular degeneration,,Cerebral Cortex/pp [Physiopathology];Child;Dimercaprol/tu [Therapeutic Use];*Electroencephalography;Epilepsy/et [Etiology];Epilepsy/pp [Physiopathology];Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Penicillamine/tu [Therapeutic Use];Pyridoxine/tu [Therapeutic Use];0CPP32S55X (Dimercaprol);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine),"Mera, A.",1969,Aug,,0,0,
1000,Diagnosis of Wilson's disease in children with liver disease. A report of two families,,"Adolescent;Adult;Brain/me [Metabolism];Ceruloplasmin/an [Analysis];Child;Copper/bl [Blood];Copper/me [Metabolism];Copper/ur [Urine];Diagnosis, Differential;Eye Manifestations;Female;*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];*Liver Cirrhosis/ge [Genetics];Liver Cirrhosis/me [Metabolism];Male;Middle Aged;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Danks, D. M.;Stevens, B. J.",1969,Jan 04,,0,0,
1001,[Treatment of Wilson's disease],,*Chelating Agents/tu [Therapeutic Use];Drug Synergism;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Pepin, B.;Barraine, R.",1968,Feb,,0,0,
1002,What Wilson's disease and its treatment have taught us about the metabolism of copper. Observations in 27 cases,,"Adolescent;Adult;Biological Transport;Ceruloplasmin/bl [Blood];Child;Child, Preschool;*Copper/me [Metabolism];Diet Therapy;Female;Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Humans;Liver/me [Metabolism];Male;Middle Aged;Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Goldstein, N. P.;Tauxe, W. N.;McCall, J. T.;Randall, R. V.;Gross, J. B.",1968,Jul,,1,1,
1003,Prevention of Wilson's disease in asymptomatic patients,,"Child;Child, Preschool;Copper;*Diet Therapy;Female;Follow-Up Studies;Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;*Penicillamine/tu [Therapeutic Use];Sibling Relations;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Arima, M.;Komiya, K.;Fujisawa, A.;Matsuoka, K.",1968,,,0,0,
1004,Toxic reactions to penicillamine in patients with Wilson's disease,,Adolescent;Antibody Formation;Child;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Walshe, J. M.",1968,Oct,,0,0,
1005,Nephrotic syndrome from penicillamine,,Antibodies;Child;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Nephrotic Syndrome/ci [Chemically Induced];Nephrotic Syndrome/im [Immunology];*Penicillamine/ae [Adverse Effects];0 (Antibodies);GNN1DV99GX (Penicillamine),"Lachmann, P. J.",1968,Oct,,0,0,
1006,Toxicity of penicillamine,,Adult;Drug Hypersensitivity;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Scheinberg, I. H.",1968,Oct,,0,0,
1007,Use of whole-body counter to study body retention of radiocopper in Wilson's disease,,"Carrier State/di [Diagnosis];*Copper/me [Metabolism];*Hepatolenticular Degeneration/me [Metabolism];Heterozygote;Homozygote;Humans;Injections, Intravenous;Penicillamine/tu [Therapeutic Use];Radioisotopes;*Radiometry;0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Hamamoto, K.;Tauxe, W. N.;Novak, L. P.;Goldstein, N. P.",1968,Nov,,0,0,
1008,Neutron activation analysis ofr copper in biological material applied to Wilson's disease,"A method for the neutron activation analysis of copper in biological material is described and applied to the diagnosis and management of four cases of Wilson's disease. Results obtained for serum and urine are in agreement with values obtained by established colorimetric techniques. The method described can estimate 10(-9) g. copper to within 10% and this sensitivity has allowed the determination of copper from biopsy material such as liver, spleen, hair, and nail.","Activation Analysis;Adolescent;Child;Child, Preschool;Colorimetry;*Copper/an [Analysis];Female;Hair/an [Analysis];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/an [Analysis];Male;Methods;Nails/an [Analysis];Penicillamine/tu [Therapeutic Use];Spleen/an [Analysis];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Fell, G. S.;Smith, H.;Howie, R. A.",1968,Jan,,0,0,
1009,Changes in Kayser-Fleischer ring during treatment of hepatolenticular degeneration,,Adult;Copper;*Cornea/me [Metabolism];Diet Therapy;Dimercaprol/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;Penicillamine/tu [Therapeutic Use];Photography;0CPP32S55X (Dimercaprol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Mitchell, A. M.;Heller, G. L.",1968,Nov,,0,0,
1010,Prophylaxis for Wilson's disease,,Hepatolenticular Degeneration/ep [Epidemiology];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;*Penicillamine/tu [Therapeutic Use];Statistics as Topic;GNN1DV99GX (Penicillamine),"Fagan, T. J.",1968,Aug 01,https://dx.doi.org/10.1056/NEJM196808012790514,0,0,
1011,Controversy in Wilson's disease,,Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),Anonymous,1968,Jun 29,,0,0,
1012,Treatment of Wilson's disease,,Adult;*Anticonvulsants/tu [Therapeutic Use];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];Prognosis;0 (Anticonvulsants);GNN1DV99GX (Penicillamine),"Richardson, J. C.",1968,Mar,,0,0,
1013,Defective urinary acidification in Wilson's disease,,"*Acidosis, Renal Tubular/et [Etiology];Adolescent;Adult;Ammonium Chloride/an [Analysis];Blood Chemical Analysis;Female;Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Hydrogen-Ion Concentration;Male;Penicillamine/tu [Therapeutic Use];Urine/an [Analysis];01Q9PC255D (Ammonium Chloride);GNN1DV99GX (Penicillamine)","Fulop, M.;Sternlieb, I.;Scheinberg, I. H.",1968,Apr,,0,0,
1014,Wilson's disease presenting with rickets,,"Child;Copper/me [Metabolism];Diagnosis, Differential;Diet Therapy;Eye Manifestations;*Hepatolenticular Degeneration/dg [Diagnostic Imaging];Hepatolenticular Degeneration/dt [Drug Therapy];Hepatolenticular Degeneration/th [Therapy];Humans;Knee/dg [Diagnostic Imaging];Male;Penicillamine/tu [Therapeutic Use];Radiography;*Rickets/dg [Diagnostic Imaging];Wrist/dg [Diagnostic Imaging];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Cavallino, R.;Grossman, H.",1968,Mar,https://dx.doi.org/10.1148/90.3.493,0,0,
1015,Prophylactic treatment of Wilson's disease,,*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Chalmers, T. C.",1968,Apr 18,,0,0,
1016,Prophylcatic use of penicillamine,,Adolescent;Female;Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Male;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Walshe, J. M.",1968,Apr 04,,0,0,
1017,Editor's choice: Wilson's disease,,*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),Anonymous,1968,Feb 15,https://dx.doi.org/10.1056/NEJM196802152780709,0,0,
1018,Prevention of Wilson's disease in asymptomatic patients,,"Adolescent;Adult;Biopsy;Ceruloplasmin/an [Analysis];Child;Child, Preschool;Copper/an [Analysis];Female;Hepatolenticular Degeneration/bl [Blood];Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/pa [Pathology];*Hepatolenticular Degeneration/pc [Prevention & Control];Humans;Infant;Liver/an [Analysis];Liver/pa [Pathology];Male;Microscopy, Electron;*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Sternlieb, I.;Scheinberg, I. H.",1968,Feb 15,https://dx.doi.org/10.1056/NEJM196802152780702,1,1,
1019,The renal clearance of amino acids in a patient with Wilson's disease during penicillamine treatment,,"Adolescent;*Amino Acid Metabolism, Inborn Errors/dt [Drug Therapy];Amino Acids/an [Analysis];Amino Acids/bl [Blood];Copper/ur [Urine];Creatinine/ur [Urine];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];0 (Amino Acids);789U1901C5 (Copper);AYI8EX34EU (Creatinine);GNN1DV99GX (Penicillamine)","Bell, G. E.;Slivka, D. C.;Huston, J. R.",1968,Jan,,0,0,
1020,Clinical uses of metal-binding drugs,,"Acid-Base Equilibrium/de [Drug Effects];Administration, Oral;Arsenic Poisoning;Calcium Metabolism Disorders/dt [Drug Therapy];Chelating Agents/ae [Adverse Effects];*Chelating Agents/pd [Pharmacology];*Chelating Agents/tu [Therapeutic Use];Deferoxamine/ad [Administration & Dosage];Deferoxamine/ae [Adverse Effects];*Deferoxamine/tu [Therapeutic Use];Dimercaprol/ae [Adverse Effects];*Dimercaprol/pd [Pharmacology];Dimercaprol/tu [Therapeutic Use];Drug Compounding;Drug Therapy;Edetic Acid/ae [Adverse Effects];*Edetic Acid/pd [Pharmacology];Edetic Acid/tu [Therapeutic Use];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Injections, Intravenous;Iron/po [Poisoning];Iron Isotopes;Lead Poisoning/dt [Drug Therapy];Male;Mercury Poisoning/dt [Drug Therapy];Ointments;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Pentetic Acid/ae [Adverse Effects];Pentetic Acid/pd [Pharmacology];Pentetic Acid/tu [Therapeutic Use];Plutonium/ae [Adverse Effects];Poisoning/dt [Drug Therapy];Radionuclide Imaging;Tablets;0 (Chelating Agents);0 (Iron Isotopes);0 (Ointments);0 (Tablets);0CPP32S55X (Dimercaprol);53023GN24M (Plutonium);7A314HQM0I (Pentetic Acid);9G34HU7RV0 (Edetic Acid);E1UOL152H7 (Iron);GNN1DV99GX (Penicillamine);J06Y7MXW4D (Deferoxamine)","Chenoweth, M. B.",1968,May-Jun,,0,0,
1021,Copper and taste sensitivity,,"Arthritis, Rheumatoid/dt [Drug Therapy];Ceruloplasmin/bl [Blood];Copper/bl [Blood];*Copper/me [Metabolism];Cystinuria/dt [Drug Therapy];Depression, Chemical;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];Pulmonary Fibrosis/dt [Drug Therapy];Scleroderma, Systemic/dt [Drug Therapy];*Taste/de [Drug Effects];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)",Anonymous,1968,Jun,,0,0,
1022,Penicillamine,,Animals;Collagen Diseases/dt [Drug Therapy];Darier Disease/dt [Drug Therapy];Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Caron, G. A.",1968,May,,0,0,
1023,Psychiatric aspects of Wilson's disease (hepatolenticular degeneration): results of psychometric tests during long-term therapy,,"Adolescent;Adult;Child;Child, Preschool;Diet Therapy;Educational Status;Female;*Hepatolenticular Degeneration/co [Complications];Hepatolenticular Degeneration/th [Therapy];Humans;Intelligence Tests;Mmpi;Male;*Mental Disorders/et [Etiology];Mental Disorders/th [Therapy];Middle Aged;Occupations;Penicillamine/tu [Therapeutic Use];*Psychological Tests;GNN1DV99GX (Penicillamine)","Goldstein, N. P.;Ewert, J. C.;Randall, R. V.;Gross, J. B.",1968,May,https://dx.doi.org/10.1176/ajp.124.11.1555,0,0,
1024,Liver-copper levels in liver disease: studies using neutron activation analysis,,"Activation Analysis;Biliary Tract Diseases/di [Diagnosis];Biopsy;Chemical and Drug Induced Liver Injury/di [Diagnosis];Cholestasis/di [Diagnosis];*Copper/an [Analysis];Copper/me [Metabolism];Diagnosis, Differential;Fatty Liver/di [Diagnosis];Hepatitis A/di [Diagnosis];Hepatolenticular Degeneration/di [Diagnosis];Humans;Hyperbilirubinemia, Hereditary/di [Diagnosis];Jaundice, Chronic Idiopathic/di [Diagnosis];Liver Cirrhosis/di [Diagnosis];Liver Cirrhosis, Biliary/di [Diagnosis];*Liver Diseases/di [Diagnosis];Liver Diseases/me [Metabolism];Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Smallwood, R. A.;Williams, H. A.;Rosenoer, V. M.;Sherlock, S.",1968,Dec 21,,0,0,
1025,Nephrotic syndrome after treatment with D-penicillamine,,Adult;Creatinine/ur [Urine];Cystinuria;Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Nephrotic Syndrome/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Proteinuria;Serum Albumin;0 (Serum Albumin);AYI8EX34EU (Creatinine);GNN1DV99GX (Penicillamine),"Felts, J. H.;King, J. S.;Boyce, W. H.",1968,Jan 06,,0,0,
1026,Blue blood,,*Ceruloplasmin/bi [Biosynthesis];*Hepatolenticular Degeneration/me [Metabolism];Humans;Penicillamine/tu [Therapeutic Use];EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),Anonymous,1967,Nov 25,,0,0,
1027,Metabolic balances of copper in patients with hepatolenticular degeneration submitted to vegetarian and mixed diets,,Adult;*Copper/me [Metabolism];*Diet Therapy;Feces/an [Analysis];Female;*Hepatolenticular Degeneration/me [Metabolism];Hepatolenticular Degeneration/th [Therapy];Humans;Male;Penicillamine/tu [Therapeutic Use];*Vegetables;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Canelas, H. M.;de Jorge, F. B.;Tognola, W. A.",1967,Aug,,0,0,
1028,Wilson's disease with aseptic meningitis and penicillamine-related cheilosis,,Adult;Blood Cell Count;Cerebrospinal Fluid Proteins;Ceruloplasmin;*Cheilitis/ci [Chemically Induced];Copper/me [Metabolism];*Gingival Diseases/ci [Chemically Induced];Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration;Humans;Liver Function Tests;Male;*Meningitis;*Penicillamine/ae [Adverse Effects];0 (Cerebrospinal Fluid Proteins);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Bennett, R. A.;Harbilas, E.",1967,Sep,,0,0,
1029,Penicillamine,,*Cystinuria/dt [Drug Therapy];*Gold/po [Poisoning];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lead Poisoning/dt [Drug Therapy];Penicillamine/ad [Administration & Dosage];Penicillamine/ae [Adverse Effects];*Penicillamine/tu [Therapeutic Use];7440-57-5 (Gold);GNN1DV99GX (Penicillamine),Anonymous,1967,Jun 30,,0,0,
1030,Studies on levels of penicillamine-induced cupriuresis in heterozygotes of Wilson's disease,,"Adolescent;Adult;Child;Child, Preschool;*Copper/ur [Urine];Female;*Hepatolenticular Degeneration/ge [Genetics];*Hepatolenticular Degeneration/ur [Urine];Humans;Male;Middle Aged;*Penicillamine/pd [Pharmacology];789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Tu, J. B.;Blackwell, R. Q.",1967,Jun,,0,0,
1031,Comparative metabolism of copper and zinc in patients with Wilson's disease (hepatolenticular degeneration),,Copper/me [Metabolism];*Cystinuria/me [Metabolism];*Hepatolenticular Degeneration/me [Metabolism];Humans;*Penicillamine/tu [Therapeutic Use];*Zinc/me [Metabolism];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);J41CSQ7QDS (Zinc),"McCall, J. T.;Goldstein, N. P.;Randall, R. V.;Gross, J. B.",1967,Jul,,0,0,
1032,Ceruloplasmin in Wilson's disease,"Ceruloplasmin was highly purified from one patient with Wilson's disease and partially purified from a second unrelated patient. The highly purified ceruloplasmin was indistinguishable from normal ceruloplasmin by electrophoresis, tryptic peptide map, oxidase activity, and copper, amino acid, and sugar composition. The partially purified ceruloplasmin was indistinguishable electrophoretically from normal ceruloplasmin. With penicillamine therapy, ceruloplasmin disappeared from the serum of the first patient; it reappeared after the drug was discontinued. The significance of this observation in regard to the basic defect in Wilson's disease is discussed.",Adult;Amino Acids/an [Analysis];Carbohydrates/an [Analysis];*Ceruloplasmin/an [Analysis];Chromatography;Copper/an [Analysis];Electrophoresis;*Hepatolenticular Degeneration/me [Metabolism];Humans;Immunoelectrophoresis;Male;Penicillamine/tu [Therapeutic Use];Trypsin;0 (Amino Acids);0 (Carbohydrates);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);EC 3-4-21-4 (Trypsin);GNN1DV99GX (Penicillamine),"Holtzman, N. A.;Naughton, M. A.;Iber, F. L.;Gaumnitz, B. M.",1967,Jun,https://dx.doi.org/10.1172/JCI105606,0,0,
1033,Picture of the month. Wilson's disease (hepato-lenticular degeneration),,Child;Diet;Dimercaprol/tu [Therapeutic Use];Eye Manifestations;Facial Expression;Female;*Hepatolenticular Degeneration/di [Diagnosis];Humans;Male;Penicillamine/tu [Therapeutic Use];Wrist;0CPP32S55X (Dimercaprol);GNN1DV99GX (Penicillamine),"Gellis, S. S.;Feingold, M.",1967,Jan,,0,0,
1034,The physiology of copper in man and its relation to Wilson's disease,,Adolescent;Adult;Child;*Copper/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Male;*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1967,Mar,,0,0,
1035,Hemolytic anemia associated with Wilson's disease,,"Adult;*Anemia, Hemolytic/et [Etiology];Ascites/et [Etiology];Child;Copper/me [Metabolism];Cornea/pp [Physiopathology];Diet Therapy;Dimercaprol/tu [Therapeutic Use];Edetic Acid/tu [Therapeutic Use];Female;*Hepatolenticular Degeneration/co [Complications];Humans;Jaundice/et [Etiology];Liver Cirrhosis/et [Etiology];Male;*Penicillamine/tu [Therapeutic Use];0CPP32S55X (Dimercaprol);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine)","Blattner, R. J.",1967,Aug,,0,0,
1036,Penicillamine-induced skin lesions. A possible example of human lathyrism,,Adult;Cysts/ci [Chemically Induced];*Drug Eruptions/et [Etiology];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Lathyrism;Male;*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Katz, R.",1967,Feb,,0,0,
1037,Decreased taste sensitivity after D-penicillamine reversed by copper administration,,"Adolescent;Adult;Aged;Arthritis, Rheumatoid/dt [Drug Therapy];Ceruloplasmin/bl [Blood];Child;Copper/bl [Blood];*Copper/tu [Therapeutic Use];Cystinuria/dt [Drug Therapy];Female;Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;Middle Aged;*Penicillamine/ae [Adverse Effects];Penicillamine/tu [Therapeutic Use];Pulmonary Fibrosis/dt [Drug Therapy];Scleroderma, Systemic/dt [Drug Therapy];*Taste/de [Drug Effects];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Henkin, R. I.;Keiser, H. R.;Jafee, I. A.;Sternlieb, I.;Scheinberg, I. H.",1967,Dec 16,,0,0,
1038,Presymptomatic Wilson's disease,,"Adolescent;Adult;Biopsy;Ceruloplasmin/bl [Blood];Child;Child, Preschool;Copper/bl [Blood];Copper/ur [Urine];Fatty Liver/co [Complications];Hepatolenticular Degeneration/co [Complications];*Hepatolenticular Degeneration/di [Diagnosis];Hepatolenticular Degeneration/ge [Genetics];Hepatolenticular Degeneration/pa [Pathology];Humans;Liver/pa [Pathology];Liver Cirrhosis/co [Complications];Middle Aged;Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine)","Levi, A. J.;Sherlock, S.;Scheuer, P. J.;Cumings, J. N.",1967,Sep 16,,0,0,
1039,Studies with radioactive copper (64Cu and 67Cu) in relation to the natural history of Wilson's disease,,Adolescent;Adult;Child;Copper/an [Analysis];Copper/bl [Blood];*Copper/me [Metabolism];*Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Liver/me [Metabolism];Middle Aged;*Penicillamine/tu [Therapeutic Use];Radioisotopes;0 (Radioisotopes);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Osborn, S. B.;Walshe, J. M.",1967,Feb 08,,0,0,
1040,A case of Wilson's disease,,Adolescent;Copper/bl [Blood];*Hepatolenticular Degeneration;Humans;Male;Zinc/bl [Blood];789U1901C5 (Copper);J41CSQ7QDS (Zinc),"Yase, Y.;Kumura, J.;Yoshimasu, F.",1966,Sep,,0,0,
1041,The effects of penicillamine therapy on uric acid metabolism in Wilson's disease,,Body Weight;Carbon Isotopes;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];*Uric Acid/me [Metabolism];0 (Carbon Isotopes);268B43MJ25 (Uric Acid);GNN1DV99GX (Penicillamine),"Sorensen, L. B.;Kappas, A.",1966,,,0,0,
1042,Penicillamine and the nephrotic syndrome,,Adolescent;Adult;Child;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Nephrotic Syndrome/ci [Chemically Induced];Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Sternlieb, I.",1966,Dec 19,,0,0,
1043,Some problems of the penicillamine action in hepatolenticular degeneration,,Adult;*Copper/me [Metabolism];Dialysis;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;In Vitro Techniques;Macroglobulins;*Penicillamine/tu [Therapeutic Use];Serum Albumin;Serum Globulins;0 (Macroglobulins);0 (Serum Albumin);0 (Serum Globulins);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Chromy, K.;Heyrovsky, A.",1966,Jun,,0,0,
1044,Nephrotic syndrome in the course of treatment of Wilson's disease with DL-penicillamine,,Child;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Kidney Glomerulus/pa [Pathology];Kidney Tubules/pa [Pathology];Liver/pa [Pathology];*Nephrotic Syndrome/ci [Chemically Induced];*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Karp, M.;Lurie, M.;Yonis, Z.",1966,Dec,,0,0,
1045,Copper content of saliva of normal subjects and treated Wilson's disease patients,,*Copper/an [Analysis];Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;Male;*Penicillamine/tu [Therapeutic Use];*Saliva/an [Analysis];Spectrophotometry;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Rice, E. W.;Goldstein, N. P.",1966,Nov,,0,0,
1046,Influence of penicillamine on the turnover of I-131-labeled ceruloplasmin in Wilson's disease,,Adult;Aged;*Ceruloplasmin/me [Metabolism];Female;Hepatolenticular Degeneration/dt [Drug Therapy];*Hepatolenticular Degeneration/me [Metabolism];Humans;Iodine Isotopes/me [Metabolism];Kinetics;Male;Middle Aged;*Penicillamine/pd [Pharmacology];Penicillamine/tu [Therapeutic Use];0 (Iodine Isotopes);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Kekki, M.;Koskelo, P.;Nikkila, E. A.",1966,Nov,,0,0,
1047,Wilson's Disease Presenting as an Acute Haemolytic Anaemia,,"*Anemia;*Anemia, Hemolytic;Child;*Copper;*Diagnosis;*Diet;*Diet Therapy;*Drug Therapy;*Hepatolenticular Degeneration;Humans;*Penicillamine;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Laurance, B. M.",1965,Aug,,0,0,
1048,Chemical Therapy of Wilson's Disease,,*Dimercaprol;*Drug Therapy;*Edetic Acid;*Hepatolenticular Degeneration;Humans;*Penicillamine;0CPP32S55X (Dimercaprol);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine),"Goldstein, N. P.;Randall, R. V.;Gross, J. B.",1965,Jul,,0,0,
1049,"[Control of the Course in Familial Wilson's Disease (Kayser-Fleischer Ring, Sunflower Cataract, Vitreous Body Pigmentation)]",,Adolescent;*Cataract;*Corneal Diseases;*Helianthus;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Pigmentation;*Pigmentation Disorders;*Vitreous Body;GNN1DV99GX (Penicillamine),"Rix, J.",1965,Jun,,0,0,
1050,The Nephrotic Syndrome as a Complication of Penicillamine Therapy for Hepatolenticular Degeneration (Wilson's Disease),,"*Drug Hypersensitivity;*Drug Therapy;*Hepatolenticular Degeneration;Humans;*Hypersensitivity, Delayed;*Nephrotic Syndrome;*Penicillamine;*Prednisone/tu [Therapeutic Use];*Toxicology;GNN1DV99GX (Penicillamine);VB0R961HZT (Prednisone)","Hirschman, S. Z.;Isselbacher, K. J.",1965,Jun,,0,0,
1051,Copper Balance Studies during the Treatment of Patients with Wilson's Disease,,Adolescent;*Asian Continental Ancestry Group;Biological Transport;*Copper;*Drug Therapy;*Electroencephalography;*Feces;*Fluids and Secretions;*Hepatolenticular Degeneration;Humans;*Minerals/me [Metabolism];*Penicillamine;*Pharmacology;*Urine;0 (Minerals);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Tu, J. B.;Blackwell, R. Q.;Watten, R. H.",1965,Jun,,0,0,
1052,"Copper Balance Studies in Wilson's Disease; Observations on the Effect of Penicillamine, Carbacrylamine Resins, and Potassium Sulfide",,*Copper;*Drug Therapy;*Feces;*Fluids and Secretions;*Hepatolenticular Degeneration;Humans;*Ion Exchange Resins;*Minerals/me [Metabolism];*Penicillamine;*Potassium;*Sulfides;*Urine;0 (Ion Exchange Resins);0 (Minerals);0 (Sulfides);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium),"Goldstein, N. P.;Randall, R. V.;Gross, J. B.;McGuckin, W. F.",1965,May,,0,1,
1053,Treatment of Hepatolenticular Degeneration (Wilson's Disease) in the Asymptomatic Stage,,*Asian Continental Ancestry Group;Child;*Copper;*Diet;*Diet Therapy;*Drug Therapy;*Electroencephalography;*Feces;*Hepatolenticular Degeneration;Humans;*Liver Function Tests;*Pathology;*Penicillamine;*Pyridoxine;*Urine;789U1901C5 (Copper);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine),"Tu, J. B.;Cooper, W. C.;Blackwell, R. Q.;Hou, T. Y.",1965,Apr,,0,0,
1054,[Wilson's Disease in the Form of a Panhemocytopenia],,*Blood;*Blood Coagulation Tests;*Copper;*Drug Therapy;*Hemorrhagic Disorders;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Thrombocytopenia;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Heinrich, F.;Kaltenbach, M.",1965,Mar 26,,0,0,
1055,Effect of Adrenocortical Steroids on the Hypercalciuria of Wilson's Disease (Hepatolenticular Degeneration),,"*Calcium;*Calcium, Dietary;*Cortisone/tu [Therapeutic Use];*Feces;*Fluids and Secretions;*Hepatolenticular Degeneration;Humans;*Hypercalciuria;*Penicillamine;*Prednisone/tu [Therapeutic Use];*Steroids;*Urine;0 (Calcium, Dietary);0 (Steroids);GNN1DV99GX (Penicillamine);SY7Q814VUP (Calcium);V27W9254FZ (Cortisone);VB0R961HZT (Prednisone)","Randall, R. V.;Goldstein, N. P.;Gross, J. B.;Rosevear, J. W.;McGuckin, W. F.",1965,Jan,,0,0,
1056,Changes of some clotting factors in hepatolenticular degeneration (Wilson's disease),,*Blood Coagulation Disorders;*Blood Coagulation Tests;*Hepatolenticular Degeneration/pp [Physiopathology];Humans;Liver Function Tests;Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Prochazka, J.;Hauftova, D.",1965,,,0,0,
1057,Effect of penicillamine on serum iron,,Adolescent;Adult;Blood;Child;*Copper/me [Metabolism];Evaluation Studies as Topic;Female;Hemoglobinometry;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Iron/me [Metabolism];Male;*Penicillamine/tu [Therapeutic Use];789U1901C5 (Copper);E1UOL152H7 (Iron);GNN1DV99GX (Penicillamine),"Walshe, J. M.;Patston, V.",1965,Dec,,0,0,
1058,[Early detection and treatment of Wilson's disease],,*Hepatolenticular Degeneration/di [Diagnosis];*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Penicillamine/tu [Therapeutic Use];GNN1DV99GX (Penicillamine),"Sternlieb, I.",1965,Apr 30,,0,0,
1059,[Renal accidents in 2 cases of Wilson's disease treated with penicillamine],,Adolescent;Adult;Female;*Hepatolenticular Degeneration/dt [Drug Therapy];Humans;*Kidney Diseases/et [Etiology];*Penicillamine/ae [Adverse Effects];GNN1DV99GX (Penicillamine),"Boudin, G.;Pepin, B.",1965,Apr 30,,0,0,
1060,Studies of Pyridoxal-Penicillamine Antagonism in the Human,,*Hepatolenticular Degeneration;Humans;*Metabolism;*Penicillamine;*Pharmacology;*Pyridoxal;*Pyridoxine;*Tryptophan;*Urine;*Xanthurenates;0 (Xanthurenates);3THM379K8A (Pyridoxal);8DUH1N11BX (Tryptophan);GNN1DV99GX (Penicillamine);KV2JZ1BI6Z (Pyridoxine),"Tu, J. B.;Blackwell, R. Q.;Cooper, W. C.;Chen, Y. H.",1964,Nov,,0,0,
1061,Hepato-Lenticular Degeneration (Wilson's Disease) Treated by Penicillamine,,Adolescent;*Alkaline Phosphatase/bl [Blood];*Bilirubin;*Blood Chemical Analysis;*Blood Protein Electrophoresis;*Cholesterol/bl [Blood];*Copper;*Dimercaprol;*Drug Therapy;*Edetic Acid;*Feces;*Hepatolenticular Degeneration;Humans;*Kidney Function Tests;*Penicillamine;Silymarin;*Spectrophotometry;*Toxicology;*Urine;0 (Silymarin);0CPP32S55X (Dimercaprol);4RKY41TBTF (silybin);789U1901C5 (Copper);97C5T2UQ7J (Cholesterol);9G34HU7RV0 (Edetic Acid);EC 3-1-3-1 (Alkaline Phosphatase);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin),"Richmond, J.;Rosenoer, V. M.;Tompsett, S. L.;Draper, I.;Simpson, J. A.",1964,Dec,,0,1,
1062,[Wilson's Disease and Its Treatment],,*Drug Therapy;*Hepatolenticular Degeneration;Humans;*Penicillamine;GNN1DV99GX (Penicillamine),"Jansen, E. G.;Ben-Gershom, E.",1964,Sep 19,,0,0,
1063,[Mode of Action of Chelator Agents in the Treatment of Hepatolenticular Degeneration],,*Chelating Agents;*Dimercaprol;*Edetic Acid;*Hepatolenticular Degeneration;Humans;*Penicillamine;0 (Chelating Agents);0CPP32S55X (Dimercaprol);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine),"Ozkan, E.;Prifti, J.;Tag, T.;Aksoy, M.;Ekmekci, A.",1964,Sep,,0,0,
1064,[Improvement in Wilson's Disease in a 17-Year-Old Girl with Continuous Penicillamine Therapy],,Adolescent;Female;*Hepatolenticular Degeneration;Humans;*Penicillamine;GNN1DV99GX (Penicillamine),"Lisa, L.;Roessler, M.;Heyrovsky, A.",1964,Oct,,0,0,
1065,[Changes in Zinc Metabolism in Hepatic Diseases],,*Hemochromatosis;*Hepatitis;*Hepatitis A;*Hepatolenticular Degeneration;Humans;*Liver Cirrhosis;*Liver Diseases;*Metabolism;*Zinc;J41CSQ7QDS (Zinc),"Caviedes, R.;Gonzalez, C.;Klinger, J.;Katz, R.",1964,Jun,,0,0,
1066,Wilson's Disease as a Gastroenterologic Problem,,"*Copper;*Diet;*Diet Therapy;*Dimercaprol;*Gastroenterology;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;*Liver Cirrhosis;*Metabolism, Inborn Errors;*Pathology;*Penicillamine;0CPP32S55X (Dimercaprol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Sternlieb, I.",1964,Sep,,0,0,
1067,Endogenous Copper Clearance in Wilson's Disease: A Study of the Mode of Action of Penicillamine,,Adolescent;*Blood;*Body Fluids;*Ceruloplasmin;Child;*Copper;*Hepatolenticular Degeneration;Humans;*Kidney Glomerulus;*Oxidation-Reduction;*Penicillamine;*Pharmacology;*Schizophrenia;*Urine;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1964,Jun,,0,0,
1068,Penicillamine Therapy for Hepatolenticular Degeneration,,"*Amenorrhea;*Avitaminosis;*Bone and Bones;*Copper;*Desensitization, Immunologic;*Diet;*Drug Eruptions;*Drug Therapy;*Eye Manifestations;Female;*Hepatolenticular Degeneration;Humans;*Hypersplenism;*Kidney;*Leukopenia;*Liver;*Metabolism;*Neurologic Manifestations;*Penicillamine;*Toxicology;789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Sternlieb, I.;Scheinberg, I. H.",1964,Sep 07,,0,0,
1069,Basal Copper Excretion in Wilson's Disease,,Adolescent;Child;*Copper;*Drug Therapy;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Urine;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Warren, C. B.;Broughton, P. M.",1964,Jun,,0,0,
1070,Filterable and Non-Filterable Serum Copper. (2). Studies with 64cu,,*Blood Chemical Analysis;*Ceruloplasmin;*Copper;*Filtration;*Hepatolenticular Degeneration;Humans;*Metabolism;*Oxidation-Reduction;*Penicillamine;*Radioisotopes;*Radiometry;*Serum Albumin;0 (Radioisotopes);0 (Serum Albumin);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Osborn, S. B.;Walshe, J. M.",1964,Apr,,0,0,
1071,Familial Hepatic Copper Storage Disease: A Variant of Wilson's Disease,,"Adolescent;*Alkaline Phosphatase/bl [Blood];*Aspartate Aminotransferases;*Bilirubin;*Blood Chemical Analysis;*Copper;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;*Pathology;*Penicillamine;*Urine;789U1901C5 (Copper);EC 2-6-1-1 (Aspartate Aminotransferases);EC 3-1-3-1 (Alkaline Phosphatase);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin)","Fisher, M. M.;Sherlock, S.",1964,Feb,,0,0,
1072,"Wilson's Disease, an Inborn Error of Metabolism and a Model of Degenerative Central Nervous System Disease",,*Central Nervous System Diseases;*Chelating Agents;*Copper;*Dimercaprol;*Hepatolenticular Degeneration;Humans;*Metabolism;*Neurodegenerative Diseases;*Penicillamine;0 (Chelating Agents);0CPP32S55X (Dimercaprol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Ravin, H. A.",1964,,,0,0,
1073,[Wilson's Disease Treated by Penicillamine],,*Ceruloplasmin;Child;*Copper;*Hepatolenticular Degeneration;Humans;*Metabolism;*Neurologic Manifestations;*Oxidation-Reduction;*Penicillamine;789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Bernheim, M.;Freycon, M. T.;Pellet, H.;Deffrenne, P.;Lamit, J.",1964,Apr-May,,0,0,
1074,Wilson's Disease,,"Child;*Clinical Laboratory Techniques;*Dimercaprol;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;*Laboratories;*Neurologic Examination;*Pathology;*Penicillamine;*Physical Examination;0CPP32S55X (Dimercaprol);GNN1DV99GX (Penicillamine)","Bumbalo, T. S.;Staub, R. U.;Villanueva, O. Q.",1964,Jun,,0,0,
1075,"D-Penicillamine, with Particular Relation to Wilson's Disease",,*Body Fluids;*Copper;*Cystinosis;*Edetic Acid;*Hepatolenticular Degeneration;Humans;*Immunologic Tests;*Lead Poisoning;*Penicillamine;*Rheumatoid Factor;*Toxicology;*Urine;789U1901C5 (Copper);9009-79-4 (Rheumatoid Factor);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine),"Scheinberg, I. H.",1964,Apr,,0,0,
1076,[Hepatocerebral or Hepatolenticular Degeneration],,"Adolescent;*Alkaline Phosphatase/bl [Blood];*Amino Acids;*Bilirubin;*Blood Coagulation Tests;*Ceruloplasmin;Child;*Copper;*Dimercaprol;*Edetic Acid;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;*Metabolism;*Oxidation-Reduction;*Penicillamine;*Urobilinogen;0 (Amino Acids);0CPP32S55X (Dimercaprol);14684-37-8 (Urobilinogen);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);EC 1-16-3-1 (Ceruloplasmin);EC 3-1-3-1 (Alkaline Phosphatase);GNN1DV99GX (Penicillamine);RFM9X3LJ49 (Bilirubin)","Aksoy, M.;Biyal, F.;Secer, F.;Cakirgoez, C.;Cetingil, A. I.",1964,,,0,0,
1077,[Wilson's Disease (Hepatocerebral Degeneration) in Children],,"Child;*Enzymes;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;*Penicillamine;0 (Enzymes);GNN1DV99GX (Penicillamine)","Weiner, C.",1964,Feb 28,,0,0,
1078,Hepatolenticular Degeneration (Wilson's Disease). Two Different Components,,"Adolescent;*Chelating Agents;Child;*Copper;*Edetic Acid;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;Middle Aged;*Neurosurgery;*Pathology;*Penicillamine;*Pharmacology;Prognosis;*Proteins/me [Metabolism];*Speech Disorders;*Tremor;0 (Chelating Agents);0 (Proteins);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine)","Denny-Brown, D.",1964,May 28,https://dx.doi.org/10.1056/NEJM196405282702203,0,1,
1079,Determination of Urinary Copper by Means of Direct Extraction with Zinc Dibenzyl Dithiocarbamate,,"*Chemistry Techniques, Analytical;*Copper;*Hepatolenticular Degeneration;Humans;*Jaundice;*Jaundice, Obstructive;*Nephrosis;*Spectrophotometry;*Urine;*Zinc;*Ziram;33RO266515 (zinc dibenzyldithiocarbamate);73D8UA974J (Ziram);789U1901C5 (Copper);J41CSQ7QDS (Zinc)","Giorgio, A. J.;Cartwright, G. E.;Wintrobe, M. M.",1964,Jan,,0,0,
1080,"Copper Balance Studies in Wilson's Disease (Hepatolenticular Degeneration). Observations on the Effect of Penicillamine, Carbo-Resin and Potassium Sulfide",,"*Charcoal;*Copper;*Hepatolenticular Degeneration;Humans;*Metabolism;*Penicillamine;*Pharmacology;*Potassium;*Resins, Plant;*Resins, Synthetic;*Sulfides;0 (Resins, Plant);0 (Resins, Synthetic);0 (Sulfides);16291-96-6 (Charcoal);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);RWP5GA015D (Potassium)","Goldstein, N. P.;Randall, R. V.;Gross, J. B.;McGuckin, W. F.",1963,,,0,1,
1081,Filterable and Non-Filterable Serum Copper. 1. The Action of Penicillamine,,*Blood Chemical Analysis;*Copper;*Dialysis;*Filtration;*Fluid Therapy;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Renal Dialysis;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1963,Dec,,0,0,
1082,[Our Experience in the Treatment of Wilson's Disease with Penicillamine],,Adolescent;*Copper;*Dimercaprol;*Edetic Acid;*Hepatolenticular Degeneration;Humans;*Neurologic Manifestations;*Penicillamine;0CPP32S55X (Dimercaprol);789U1901C5 (Copper);9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine),"Boudin, G.;Pepin, B.;Lauras, A.;Barraine, R.",1963,Jul,,0,0,
1083,"[Considerations on Splenectomy and on Penicillaminic Therapy in a Case of ""Abdominal Form"" of Hepatolenticular Degeneration]",,*Abdomen;*Hepatolenticular Degeneration;*Penicillamine;*Spleen;*Splenectomy;GNN1DV99GX (Penicillamine),"Bisiach, E.",1963,Jun,,0,0,
1084,Current Therapeutics. 192. Penicillamine,,*Chemical Phenomena;*Chemistry;Child;*Copper;*Cystinosis;*Cystinuria;*Hepatolenticular Degeneration;Humans;*Lead Poisoning;*Mercury Poisoning;*Penicillamine;*Pharmacology;*Toxicology;*Waldenstrom Macroglobulinemia;789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Walshe, J. M.",1963,Dec,,0,0,
1085,Hepatolenticular Degeneration: Observations on a Case Treated with D-Penicillamine,,*Blood Chemical Analysis;*Ceruloplasmin;Child;*Copper;*Electrolytes;*Hepatolenticular Degeneration;Humans;*Liver;*Neurologic Manifestations;*Pathology;*Penicillamine;*Urine;0 (Electrolytes);789U1901C5 (Copper);EC 1-16-3-1 (Ceruloplasmin);GNN1DV99GX (Penicillamine),"Herring, V. G., 3rd;Klatskin, G.;Brandt, I. K.",1963,Oct,,0,0,
1086,Study of Wilson's Disease in Taiwan,,"*Asian Continental Ancestry Group;China;*Copper;*Diet;*Diet Therapy;*Genetics, Medical;*Hepatolenticular Degeneration;Humans;*Minerals/me [Metabolism];*Penicillamine;*Research;Taiwan;0 (Minerals);789U1901C5 (Copper);GNN1DV99GX (Penicillamine)","Tu, J. B.;Hung, T. P.;Lin, T. Y.;Blackwell, R. Q.;Watten, R. H.;Cooper, W. C., Jr.",1963,Sep,,0,0,
1087,Medical Grand Rounds from the University of Alabama Medical Center. Case 9: Wilson's Disease,,*Chelating Agents;*Drug Hypersensitivity;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Teaching Rounds;*Toxicology;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Williamson, C. I.;Blakey, C. L.;Little, S. C.;Dempsey, H.;Branscomb, B. V.;Butterworth, C. E.;Pittman, J. A.",1963,Oct,,0,0,
1088,Penicillamine and Mixed Disulphide Excretion in Wilson's Disease,,*Cysteine;*Cystinuria;*Disulfides;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Sulfides;0 (Disulfides);0 (Sulfides);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Hartley, B. S.;Walshe, J. M.",1963,Aug 31,,0,0,
1089,[Our experience with the treatment of Wilson's disease by penicillamine],,*Chelating Agents;*Hepatolenticular Degeneration;Humans;*Neurologic Manifestations;*Penicillamine;0 (Chelating Agents);GNN1DV99GX (Penicillamine),"Boudin, G.;Pepin, B.;Barraine, R.",1963,May 3-10,,0,0,
1090,[Treatment of Wilson's disease with penicillamine and guajacuran],,*Chelating Agents;*Guaifenesin;*Hepatolenticular Degeneration;Humans;*Penicillamine;0 (Chelating Agents);495W7451VQ (Guaifenesin);GNN1DV99GX (Penicillamine),"Blehova, B.;Heyrovsky, A.;Nebudova, J.;Votava, Z.",1963,Jan,,0,0,
1091,[Method and surveillance of treatment by penicillamine during hepatolenticular degeneration and in poisonings. (Apropos of 3 cases)],,*Chelating Agents;*Copper;*Hepatolenticular Degeneration;Humans;*Lead Poisoning;*Penicillamine;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Pieri, J.;Tronconi;Moreau;Eisinger",1963,,,0,0,
1092,"[On 2 family lines with Wilson's pseudosclerosis. Clinical course and therapy, with special reference to combined therapy with BAL, penicillamine and vitamin E]",,"*Chelating Agents;*Dimercaprol;*Hepatolenticular Degeneration;Humans;*Penicillamine;*Psychotherapy, Multiple;*Vitamin E;0 (Chelating Agents);0CPP32S55X (Dimercaprol);1406-18-4 (Vitamin E);GNN1DV99GX (Penicillamine)","Nishi, N.;Iizuka, R.;Fujii, H.;Kawamura, K.;Takahata, N.",1963,Jan,,0,0,
1093,[Ocular manifestations of Wilson's disease treated by penicillamine],,*Chelating Agents;*Copper;*Eye Manifestations;*Hepatolenticular Degeneration;Humans;*Penicillamine;0 (Chelating Agents);789U1901C5 (Copper);GNN1DV99GX (Penicillamine),"Michiels, J.;Laterre, C.;Dumoulin, D.",1963,,,0,0,
1094,Treatment of Wilson's disease (hepatolenticular degeneration) with DL-penicillamine,,*Hepatolenticular Degeneration/th [Therapy];Humans;*Penicillamine;Valine/aa [Analogs & Derivatives];GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine),"Goldstein, N. P.;Randall, R. V.;Gross, J. B.;Rosevear, J. W.;Mc, Guckin Wf",1962,Apr,,0,0,
1095,Treatment of Wilson's disease (hepatolenticular degeneration) with DL-penicillamine,,*Hepatolenticular Degeneration/th [Therapy];Humans;*Penicillamine;*Penicillins/th [Therapy];0 (Penicillins);GNN1DV99GX (Penicillamine),"Goldstein, N. P.;Randall, R. V.;Gross, J. B.;Rosevear, J. W.;Mc, Guckin Wf",1961,,,0,0,1094
1096,[The use of penicillamine as a diagnostic aid in hepatolenticular degeneration (Wilson's disease)],,*Hepatolenticular Degeneration/di [Diagnosis];Humans;*Penicillamine;Valine/aa [Analogs & Derivatives];GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine),"Blehova, B.;Heyrovsky, L.",1961,Sep,,0,0,
1097,[Essential hepatorenal form of Wilson's disease in a brother and a sister and its treatment with penicillamine],,Child;Female;*Hepatolenticular Degeneration;Humans;Infant;Male;*Penicillamine;*Siblings;Valine/aa [Analogs & Derivatives];GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine),"Monnet, P.;Gauthier, J.;Cotte, J.;Vallon, J. J.;Nicolas, A.;Ruitton, Ugliengo",1961,,,0,0,
1098,"Effect of D,L-penicillamine on the urinary excretion of copper and calcium in hepatolenticular degeneration (Wilson's disease)",,*Calcium/ur [Urine];*Copper/ur [Urine];*Hematologic Tests;*Hepatolenticular Degeneration/ur [Urine];Humans;*Penicillamine;Valine/aa [Analogs & Derivatives];789U1901C5 (Copper);GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine);SY7Q814VUP (Calcium),"Litin, R. B.;Goldstein, N. P.;Randall, R. V.;Power, M. H.;Diessner, G. R.",1960,Feb,,0,0,
1099,[On Wilson's disease. Also a contribution on penicillamine therapy],,*Hepatolenticular Degeneration;Humans;*Penicillamine;Valine/aa [Analogs & Derivatives];GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine),"Lange, J.;Hager, H.",1960,,,0,0,
1100,Treatment of Wilson's disease with penicillamine,,*Hepatolenticular Degeneration/th [Therapy];Humans;*Penicillamine;Valine/aa [Analogs & Derivatives];GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine),"Walshe, J. M.",1960,Jan 23,,0,0,
1101,[Physiopathological study of a case of Wilson's disease. Treatment with penicillamine],,*Hepatolenticular Degeneration;Humans;*Medical Records;*Penicillamine;Valine/aa [Analogs & Derivatives];GNN1DV99GX (Penicillamine);HG18B9YRS7 (Valine),"Gregoire, F.;Toussaint, D.;Vis, H.;Gregoire, P. E.",1960,Nov-Dec,,0,0,
1102,[The effects of penicillamine and versenate in the treatment of Wilson's disease and lead poisoning],,Cysteine/aa [Analogs & Derivatives];*Edetic Acid/th [Therapy];*Hepatolenticular Degeneration/th [Therapy];Humans;*Lead Poisoning;*Penicillamine;9G34HU7RV0 (Edetic Acid);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Seignette, W. T.;Haanen, C. A.;Jansen, A. P.;Majoor, C. L.",1959,Jun,,0,1,
1103,Clinical studies with penicillamine in hepatolenticular degeneration,,*Biomedical Research;Cysteine/aa [Analogs & Derivatives];*Hepatolenticular Degeneration;*Penicillamine;GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Seven, M. J.;Kliman, B.;Peterson, R. E.",1959,Jan,,0,0,
1104,Effects of penicillamine and dimercaprol on turnover of copper in patients with Wilson's disease,,*Copper/me [Metabolism];Cysteine/aa [Analogs & Derivatives];*Dimercaprol/pd [Pharmacology];*Hepatolenticular Degeneration/me [Metabolism];Humans;*Penicillamine;0CPP32S55X (Dimercaprol);789U1901C5 (Copper);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Osborn, S. B.;Walshe, J. M.",1958,Jan 11,,0,1,
1105,The treatment of hepatolenticular degeneration with penicillamine; with report of two cases,,Cysteine/aa [Analogs & Derivatives];*Hepatolenticular Degeneration/th [Therapy];Humans;*Penicillamine;GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Fister, W. P.;Boulding, J. E.;Baker, R. A.",1958,Jan 15,,0,0,
1106,"Penicillamine, a new oral therapy for Wilson's disease",,Cysteine/aa [Analogs & Derivatives];*Dimercaprol/tu [Therapeutic Use];*Hepatolenticular Degeneration/th [Therapy];Humans;*Penicillamine;0CPP32S55X (Dimercaprol);GNN1DV99GX (Penicillamine);K848JZ4886 (Cysteine),"Walshe, J. M.",1956,Oct,,0,0,
1107,Mutations of zinc finger E-box binding homeobox 2 (ZEB2) leading to develop connecting tissue disorder similar to Ehlers-Danlos syndrome,"Mowat-Wilson syndrome (MOWS, OMIM#235730) is a multiple congenital anomaly syndrome characterized by distinctive facial appearance, intellectual disability, microcephaly, and variable congenital malformations, including congenital heart defects and Hirschsprung disease. It is caused by heterozygous loss of function mutations or deletions in ZEB2. Whereas no skin manifestation of MOWS has been documented, we found for the first time that MOWS patients harbored hyperextensibility and fragility of the skin, being similar to Ehlers-Danlos syndrome (EDS). Transmission electron microscopy analysis of skin from a MOWS patient revealed dermal collagen fibrils with markedly decreased diame-ters. To study the role of ZEB2 in collagenogenesis, ZEB2 conditional knockout (cKO) mice were generated by crossing ZEB2<sup>flox</sup>/<sup>flox</sup> mice with Cre mice under the control of prx 1 promoter, to target the mesoderm. Newborn ZEB2 cKO mice were small and demonstrated abnormalities in the teeth and scalp bone. Notably, the skin of ZEB2 cKO mice appeared flabby and hyperextesiblity, and histologic examination revealed hypoplasia of the dermis. qRT-PCR analy-sis revealed that dermal fibroblasts (DFs) from ZEB2 cKO mice expressed decreased collagen 1 and 3 genes but increased MMP13 gene. Electron micrographsofthe dermisof ZEB2 cKO mice showed collagen fibrils with abnormally small diameters, resembling them in a MOWS patient. Finally, ZEB2 cKO mice showed impaired fibrogenesis by subcutaneous injection of bleomycin. These results suggest that ZEB2 contributes to de novo and induced collageno-genesis, and more importantly, that MOWS is relevant to a novel subtype of EDS.",animal model;animal tissue;collagen fibril;dermis;E box element;Ehlers Danlos syndrome;fibroblast;fibrogenesis;gene mutation;histology;homeobox;hypoplasia;injection;knockout mouse;mesoderm;mouse;newborn;nonhuman;promoter region;real time polymerase chain reaction;scalp;skin fragility;skin manifestation;tooth malformation;transmission electron microscopy;bleomycin;collagen type 1;collagen type 3;collagenase 3;endogenous compound;zinc finger protein,"Teraishi, M.;Takaishi, M.;Nakajima, K.;Mizuno, S.;Hiraki, Y.;Fukada, T.;Shimoda, S.;Asada, Y.;Wakamatsu, N.;Furukawa, T.;Sano, S.",2016,October,http://dx.doi.org/10.1016/j.jdermsci.2016.08.416,0,0,
1108,Psychosis in Wilson's disease: An unusual presentation of bipolar affective disorder,"Psychosis is a rare but recognised symptom of the neurological effects of Wilson's Disease [1]. We report on the presentation of a 55 year old woman, C, admitted after displaying a decline in mental state. On initial assessment in the Emergency Department she was restrained by security and police and was aggressive in her behaviour. She was quietly spoken, voicing paranoid persecutory delusions, euthymic with labile affect, alternating between anger and tearfulness, and displayed disinhibited affection, behaving in a frontal manner. She lacked insight completely. She was detained for a period of assessment under Section 2 of the Mental Health Act (MHA) 2007. C. had multiple previous admissions under the MHA. Past primary diagnoses included Wilson's Disease and Bipolar Affective Disorder (BPAD). Secondary to her Wilson's Disease she had developed Liver Cirrhosis, abdominal varices, portal and pulmonary hypertension (WHO functional class II) with massive splenomegaly. She has a history of behavioural outbursts; acquiring a forensic history for assault on staff, police and family members, and drunken and disorderly behaviour. In the weeks leading to admission she had stopped taking all of her medication including her Penicillamine. A. neurological examination showed ataxia with a wide-based gait and minor bradykinesia. C did not have a wing-flapping tremor, dystonia or myoclonus. All other findings on neurological examination were normal. She had a copper level of 1.7 imol/L, caeruloplasmin of 0.04 g/L and a bilirubin of 50 imol/L. Full blood count demonstrated pancytopenia, and extended blood screen highlighted low calcium with vitamin D deficiency. A CT of her head displayed hypodensity in the putamen, which was worse on the left. There was no mass, infarct or infectious process obvious to explain the lesions. This was consistent with an MRI brain performed a number of months prior to the admission, which demonstrated hyperintensity of both putamina. Such changes are recognised to be associated with Wilson's Disease [2]. These findings, along with C's behaviours indicative of frontal lobe involvement, suggested to the managing team a diagnosis of psychosis secondary to neurological Wilson's Disease. She was treated effectively with Paliperidone depot (100 mg monthly), 4 mg Risperidone ON and Penicillamine (750 mg BD) along with her usual medication for liver cirrhosis. To date she remains stable and has not been readmitted. The MRI and CT brain findings along with C's longstanding Wilson's Disease brought into question her diagnosis of BPAD. Upon casenote review her previous presentations had included behavioural and neurological examination findings consistent with neurological sequelae of Wilson's Disease. Psychiatric symptoms within Wilson's Disease are common, with one study finding 20% of WD patients had seen a psychiatrist [3]. Predominantly personality change and depression are typical features, psychosis being a rare but recognised feature. Psychiatric symptoms are a recognised side effect of Penicillamine, clouding diagnostic clarity [1]. Literature reviews suggest that Wilson's Disease may present with only psychiatric symptoms for many years before neurological or hepatic symptoms develop. Wilson's Disease should therefore not be discounted in unusual presentations of psychosis such as C's case.",adult;adverse drug reaction;anger;assault;ataxia;bipolar disorder;blood cell count;bradykinesia;case report;diagnosis;dystonia;emergency ward;female;flapping tremor;frontal lobe;gait;head;human;infarction;liver cirrhosis;mental health;middle aged;myoclonus;neurologic examination;neurological complication;nuclear magnetic resonance imaging;pancytopenia;paranoia;persecutory delusion;personality disorder;police;portal hypertension;psychiatrist;pulmonary hypertension;putamen;side effect;splenomegaly;staff;varicosis;vitamin D deficiency;Wilson disease;wing;calcium;ceruloplasmin;endogenous compound;penicillamine;risperidone,"Black, L. F.;Underwood, J. F. G.",2017,October,,0,0,
1109,Optical coherence tomography as a marker of neurodegeneration in patients with Wilson's disease,"Wilson's disease (WD) is an inherited autosomal recessive disorder that leads to pathological copper accumulation in different organs. Optical coherence tomography (OCT) is proposed as a marker of neurodegeneration in many neurological diseases. Thinning of the total retinal nerve fiber layer (RNFL) and macular thickness (Mth) examined by OCT was detected in patients with WD, especially those with brain magnetic resonance imaging changes. The aim of this study was to evaluate the relationship between OCT parameters and the progression of neurological signs measured by the Unified Wilson's Disease Rating Scale (UWDRS) in patients with WD. Consecutive patients with WD admitted to the Department of Neurology underwent OCT to assess the thickness of the macula and total RNFL. Patients also had neurologic assessments according to the UWDRS part III. Patients were divided into two groups based on the presence (UWDRS+) and absence (UWDRS-) of neurological symptoms. Fifty-eight patients (34 females, 24 males) were enrolled. Mean duration of treatment was 9 years (standard deviation [SD], +/-10.8). The mean UWDRS score at the time of study was 8.4 (range 1-52; SD +/-13.9) points. Total RNFL as well as macula thickness were significantly decreased in the UWDRS+ group versus the UWDRS- group. A significant negative correlation was found between OCT parameters (RNFL and Mth measurements) and neurological impairment according the UWDRS scale. This study confirms that OCT may be a useful tool for measuring the degree of neurodegeneration in patients with WD, and may play role in monitoring disease progression. Copyright © 2017, The Author(s).",Neurodegeneration;Optical coherence tomography;Unified Wilson's Disease Rating Scale;Wilson's disease;adult;article;assessment of humans;controlled study;disease course;female;human;intraocular pressure;macular thickness;major clinical study;male;nerve cell;nerve degeneration/di [Diagnosis];nerve degeneration/dt [Drug Therapy];nuclear magnetic resonance imaging;retinal nerve fiber layer thickness;slit lamp microscopy;Unified Wilson Disease Rating Scale;visual acuity;Wilson disease;penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Langwinska-Wosko, E.;Litwin, T.;Dziezyc, K.;Karlinski, M.;Czlonkowska, A.",2017,01 Dec,http://dx.doi.org/10.1007/s13760-017-0788-5,0,0,
1110,Diagnosis and management of fulminant Wilson's disease: a single center's experience,"Background: Medical therapy is rarely effective in patients with fulminant Wilson's disease (FWD). Liver transplantation is limited by the lack of donor liver in most patients with FWD at the time of diagnosis. New Wilson's index, model for end-stage liver disease (MELD) and Child-Pugh score are useful tools for decision-making of liver transplantation; however, none of them is an independent decisive tool. It is worthwhile to explore a more effective and practical therapeutic strategy and reevaluate the prediction systems for patients with FWD. Methods: Nine patients with FWD associated with hemolytic crisis and fulminant hepatic failure (FHF) were investigated. The clinical presentation, prognostic score and medical therapies of the patients were analyzed. Results: In 7 of the 9 patients with FWD who received the comprehensive therapy of corticosteroid, copper-chelating agent (dimercaptopropansulfonate sodium) and therapeutic plasma exchange (TPE), 6 patients recovered from FHF. The remaining one had been improved through the comprehensive therapy but died of septicemia 51 days later. Two patients with spontaneous bacterial peritonitis (SBP) died from liver failure in three or five hospital days without plasma exchange or chelating therapy. All of the 9 patients with FWD presented with acute hepatic failure, severe jaundice and mild to severe hemolytic anemia. No marked difference in the incidence of severe hemolytic anemia was detected between the survival and deceased groups. However, the incidence and the degree of hepatic encephalopathy (HE) in the non-survival group were higher than those in the survival group. Unlike the deceased group, the survival group had no complications induced by bacterial infection. Compared to new Wilson's index, Child-Pugh score and MELD score, the variation of prothrombin activity (PTA) between the survival and deceased groups was more evident. Conclusion: For patients with FWD, the episode of severe hepatic encephalopathy or/and spontaneous bacterial peritonitis indicates worse prognosis, and PTA is a recommendable predictor. An emergent liver transplantation should be considered for patients whose PTA is below 20%, or for those with severe HE or/and SBP. The comprehensive therapy of corticosteroid, copper-chelating agent and TPE is effective for patients without SBP and whose PTA is higher than 20%. Copyright © 2015, Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag Berlin Heidelberg.",decoppering;dimercaptopropansulfonate sodium;fulminant hepatic failure;therapeutic plasma exchange;Wilson's disease;acute liver failure;adolescent;adult;alanine aminotransferase blood level;albumin blood level;albumin dialysis;article;aspartate aminotransferase blood level;bacterial peritonitis;cause of death;child;Child Pugh score;clinical article;clinical feature;copper metabolism;disease severity;female;fever/si [Side Effect];fulminant Wilson disease/di [Diagnosis];fulminant Wilson disease/dt [Drug Therapy];fulminant Wilson disease/th [Therapy];hemolytic anemia;hepatic encephalopathy;human;incidence;jaundice;liver function;liver function test;male;Model For End Stage Liver Disease Score;plasmapheresis;prothrombin time;school child;scoring system;septicemia;skin allergy/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];Wilson Index;young adult;alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];chelating agent/iv [Intravenous Drug Administration];dexamethasone/iv [Intravenous Drug Administration];dimercaptopropansulfonate sodium/ae [Adverse Drug Reaction];dimercaptopropansulfonate sodium/dt [Drug Therapy];dimercaptopropansulfonate sodium/iv [Intravenous Drug Administration];methylprednisolone/dt [Drug Therapy];methylprednisolone/iv [Intravenous Drug Administration];penicillamine;serum albumin/ec [Endogenous Compound];unclassified drug,"Tian, Y.;Gong, G. Z.;Yang, X.;Peng, F.",2016,01 May,http://dx.doi.org/10.1007/s12519-015-0026-2,0,0,
1111,Dystonic dysarthria in Wilson disease: Efficacy of zolpidem,"Wilson disease (WD) is a rare genetic disorder characterized by copper overload in the liver and the brain. Neurological presentations are mainly related to the accumulation of copper in the basal ganglia, the brainstem, and the cerebellum. Dysarthria is a frequent symptom, with dystonic, spastic, or parkinsonian components and is usually resistant to medical or voice rehabilitation therapies. Here, we report the case of a patient with WD diagnosed at the age of 12, who presented a severe and constant dysarthria from dystonic origin which was unresponsive to benzodiazepines and anticholinergic drugs. When she was 25-year-old, she tried zolpidem at bedtime for sleeping difficulties and reported a paradoxical effect of this drug on her voice. To confirm the effect of zolpidem on her dystonic dysarthria, we realized a full evaluation of her dysarthria at baseline without zolpidem and after 4 days of treatment by 10 mg twice a day. Lexical access was evaluated by the semantic fluency; dysarthria by the Intelligibility Score, the spontaneous speech and reading rates, the maximum phonation time on the sustained vowel [a] and by a perceptive evaluation. Two hours after the intake of zolpidem, improvement of all the parameters tested, with the exception of the maximum phonation time, was observed. Semantic fluency increased by 59%, the spontaneous speech rate by 88% and the reading rate by 76%. General dystonia remained unchanged and the tolerance of zolpidem was satisfactory. Since then, the patient takes zolpidem 5 mg five times a day, and 4 years later shows persistent improvement in oral communication and a good drug tolerance. In this single-case study, we showed that regular daytime intake of zolpidem could have a persisting effect on a complex dystonic dysarthria that was resistant to usual medical treatments. Copyright © 2017 Poujois, Pernon, Trocello and Woimant.",Benzodiazepines;Copper;Dysarthria;Dystonia;Imidazopyridine;Voice therapy;Wilson disease;Zolpidem;adult;aggressiveness;apathy;article;case report;clinical article;drug efficacy;drug substitution;drug withdrawal;dysarthria/th [Therapy];dysphagia/su [Surgery];dystonia/dt [Drug Therapy];exon;female;globus pallidus;human;irritability;jejunostomy;mesencephalon;nephrotic syndrome/si [Side Effect];nuclear magnetic resonance imaging;putamen;sleep disorder/dt [Drug Therapy];speech therapy;thalamus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];benzodiazepine derivative/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];copper/ec [Endogenous Compound];glutamine/ec [Endogenous Compound];histidine/ec [Endogenous Compound];methionine/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];threonine/ec [Endogenous Compound];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zolpidem/dt [Drug Therapy],"Poujois, A.;Pernon, M.;Trocello, J. M.;Woimant, F.",2017,31 Oct,http://dx.doi.org/10.3389/fneur.2017.00559,0,0,
1112,Oromandibular Dystonia in Wilson's Disease,"Background: Movement disorder is common in Wilson's disease (WD), but there is no report on oromandibular dystonia (OMD). We report on frequency, severity, and MRI correlation of OMD in Wilson's disease with neurological manifestations (WDNM) and its response to treatment. Methods: Consecutive WDNM patients were included and their clinical, hematological, serum chemistry, and MRI findings were noted. Neurological severity of WD and OMD were assessed. Burke-Fahn-Marsden (BFM) score for dystonia was noted. Patients were treated with penicillamine, zinc, and multiple antidystonic drugs. Clinical improvement at 3 and 6 months was noted. Results: Overall, 61 of 67 (91%) WDNM patients had OMD, whose median age was 13.5 years. Median severity of OMD was 2.5 (range, 1-4). Thirteen patients were anarthric and 12 unable to eat. Severity of OMD correlated with drooling (r = 0.29; P = 0.02), BFM score (r = 0.63; P < 0.001), pancytopenia (r = -0.26; P = 0.04), and serum ceruloplasmin (r = 0.33; P = 0.01), but not with location and number of MRI lesions. Compared to baseline, severity of OMD improved at 6 months (P < 0.001), but not at 3 months. None became asymptomatic. Improvement in OMD paralleled with improvement in severity grade of WDNM (r = 0.26; P = 0.04) and with BFM score (r = 0.31; P = 0.02). Conclusion: OMD was a common manifestation of WDNM occurring in 91% patients, and OMD improved partially over the study period. Copyright © 2015 International Parkinson and Movement Disorder Society.",dystonia;movement disorder;mri;oromandibular dystonia;outcome;penicillamine;Wilson's disease;adolescent;adult;article;Burke Fahn Marsden score;child;disease severity;drug withdrawal;follow up;human;hypersalivation;major clinical study;Mini Mental State Examination;nuclear magnetic resonance imaging;pancytopenia;priority journal;retrospective study;scoring system;Wilson disease;ceruloplasmin/ec [Endogenous Compound];clonazepam;diazepam;tetrabenazine;trihexyphenidyl;zinc sulfate,"Kalita, J.;Ranjan, A.;Misra, U. K.",2015,September,http://dx.doi.org/10.1002/mdc3.12171,0,1,
1113,Imaging and Clinical Worsening After Penicillamine Treatment in Wilson's Disease,,dystonia;penicillamine;Wilson's disease;adult;Atm gene;basal ganglion;case report;clinical article;demyelination;DNA determination;drug withdrawal;gene;gene mutation;general condition deterioration;human;imaging;laboratory test;liver dysfunction/di [Diagnosis];male;middle cerebellar peduncle;note;nuclear magnetic resonance imaging;oromandibular dystonia;parkinsonism;priority journal;side effect/si [Side Effect];thalamus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Teive, H. A. G.;de Carvalho, A.;Munhoz, R. P.;Moro, A.;Moscovich, M.;Barbosa, E. R.",2015,December,http://dx.doi.org/10.1002/mdc3.12181,0,0,
1114,Wilson's disease: What has been confirmed in diagnostic and therapy?. [German],"Wilson's disease (WD) is a rare autosomal recessive disorder characterized by abnormal copper accumulation. Presenting a broad variety of phenotypes and, thus, being a chameleon within the group of metabolic diseases, the manifold clinical symptoms of WD can include hepatologic, neurologic, and psychiatric manifestations. Early onset presentations in infancy and late-onset manifestations in adults older than 70 years of age have been described. If the typical laboratory blood test values are missing, the diagnosis of WD may be difficult and often involves a combination of different parameters. Novel test methods like the identification of the relative exchangeable copper have not been validated within a sufficient cohort of WD patients as of yet and therefore do not currently play a crucial role within the clinical setting. Consequently any patient with reasonable suspected diagnosis of WD needs to be presented to a (pediatric) gastroenterologist and/or (pediatric) neurologist. Different medical treatments including drugs such as copper chelating agents are commonly used in the clinical setting. Liver transplantation may be the ultima ratio in selected patients. Dietary changes involving a low copper diet play only a minor role. Due to the fact the use of tetrathiomolybdate is still not approved, the treatment of advanced and progressive neurologic symptoms remains a major challenge. In any case, life-long medical supervision and treatment governed by a specialist is absolutely essential. Early diagnosis and early and life-long treatment lead to better prognoses and do not negatively influence the overall life expectancy. Copyright © 2017 Springer Medizin Verlag GmbH","Chelating agents, copper;Liver transplantation;Penicillamine;Tetrathiomolybdate;Zinc;adult;blood;child;cohort analysis;diagnosis;diet;early diagnosis;gastroenterologist;human;infancy;life expectancy;neurologic disease;neurologist;prognosis;tetrathiomolybdic acid","Pfister, E. D.",2017,02 Nov,http://dx.doi.org/10.1007/s00108-017-0342-9,0,0,
1115,"Evolving Perspectives in Wilson Disease: Diagnosis, Treatment and Monitoring","Wilson disease (WD), the autosomal recessively inherited copper overload disorder, remains a diagnostic and therapeutic challenge. In the last decade, direct sequencing of the affected gene ATP7B became commercially available, but interpretation of the results still requires careful attention. Thus, a combination of tests reflecting the disturbed copper metabolism is needed to make the final diagnosis. Because of the low disease frequency, the existing treatment concepts are not based on controlled trails. Here, recent outcome reports of larger cohort studies challenge the recommended therapies and call for individualized treatment strategies. The notion, that certain medical regimens may either be insufficient to upkeep copper homeostasis or may lead to a clinically relevant overtreatment, demand a continuous monitoring of patients even after decades of therapy. In this article, we review current diagnostic and therapeutic approaches in WD. © 2011 Springer Science+Business Media, LLC.",atp7b;Copper deficiency;Copper overload;D-penicillamine;Genetic testing;Liver;Overchelation;Trientine;Wilson Disease;Wilson's disease;Zinc therapy;monitoring;diagnosis;therapy;genetic screening;homeostasis;patient;copper metabolism;human;gene;morbidity;cohort analysis;commercial phenomena;copper;zinc;penicillamine,"Weiss, K. H.;Stremmel, W.",2011,,http://dx.doi.org/10.1007/s11894-011-0227-3,0,0,
1116,Decompensated Liver Disease in a Patient with Neurocysticercosis,,abdominal distension;adult;article;ascites/dt [Drug Therapy];brain edema/dt [Drug Therapy];case report;clinical feature;computer assisted tomography;decompensated liver cirrhosis;differential diagnosis;drug dose increase;epigastric discomfort;human;international normalized ratio;leg edema/dt [Drug Therapy];liver cirrhosis;liver function test;male;middle aged;Model For End Stage Liver Disease Score;neurocysticercosis/dt [Drug Therapy];priority journal;tonic clonic seizure/dt [Drug Therapy];urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];acetylsalicylic acid;alanine aminotransferase/ec [Endogenous Compound];albendazole/dt [Drug Therapy];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];dexamethasone/dt [Drug Therapy];furosemide/dt [Drug Therapy];levetiracetam/dt [Drug Therapy];spironolactone/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration],"Safadi, S.;Mohamed, A. M.;Altamimi, B. A.;Strickland, R. G.;McCarthy, D. M.",2017,01 Jun,http://dx.doi.org/10.1007/s10620-017-4590-2,0,0,
1117,Significant heterogeneity in the diagnosis and management of wilson disease (WD): Results from a large spanish registry,"There are areas of uncertainty regarding diagnostic tools and therapeutic strategies in patients diagnosed with WD, one of the few rare diseases in Hepatology. Our aim was to assess in a large multicenter Spanish Registry whether the approach to WD diagnosis and management is homogenous among centers. METHODS: Observational, descriptive study of the GEMHEP (Spanish Group of Women Hepatologists) in which clinical and laboratory data on 126 WD patients followed at 28 Spanish hospitals were collected. RESULTS: Median age at diagnosis was 20 (range: 1-74) years, 60% were men. Median follow-up (FU) was 16 yrs (1-44). The most frequent form of presentation was hepatic (70%; median age: 18 yrs) followed by mixed (12%, median age: 33 yrs) and neurological (8%; median age: 23 yrs). In the remainder 10%, the diagnosis was done through family screening. Kayser-Fleisher ring and cirrhosis were present at diagnosis in one third of cases. Discordant results were observed regarding diagnostic non-invasive laboratory parameters in 58% of cases; while ceruplasmin (CP) levels were decreased in 88% of cases, 24hr cupruria was greater than 100 mcg/24hrs in only 43% of patients at diagnosis. Most patients had intrahepatic copper concentration performed with results compatible with WD in 79%. Genetic testing was done in half of the patients with mutations compatible with WD found in the majority (83%). DP and Zinc (Zn) were the most common initial therapies, used as single agents in 76% and 18% of patients, respectively. Treatment was modified during follow up in half of the patients at a mean of 8 yrs, mostly due to switch to a Zn-maintenance therapy (47% at a median of 7 yrs) or toxicity (39%, at a median of 2 yrs). Despite good adherence observed in 90% of patients, up to one third of patients had abnormal liver enzymes at last FU visit. Overweight and hypertension were more frequently present in these patients (p=.006 and 0.05). Additional data is being collected to perform a more thorough analysis of factors associated with lack of normalization of liver enzymes. CONCLUSIONS: Discordant results regarding standard tests for WD diagnosis was frequent in our multicenter Spanish cohort. This variability may be due to lack of reproducibility between laboratories forcing to carry out invasive techniques in a substantial number of patients. Although the majority of patients start treatment with DP, switching to Zn due to either maintenance protocol and/or toxicity is the norm. In one third of cases, a complete normalization of liver enzymes was not reached, perhaps due to unrelated causes.",adult;diagnosis;drug therapy;female;follow up;genetic screening;human;hypertension;liver cirrhosis;maintenance therapy;major clinical study;male;multicenter study;mutation;obesity;register;reproducibility;Spaniard;toxicity;Wilson disease;young adult;liver enzyme;zinc,"Berenguer, M.",2017,October,,0,1,
1118,Clinical presentation and outcome of wilson's disease patients in a monocentric cohort of liver reference center,"Introduction. Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism, leading to liver cirrhosis and neuropsychological deterioration. Clinical data on larger cohorts are limited, owing to low disease frequency. Aim. Determine clinical presentation and outcome of patients with Wilson's disease in a cohort of patients from a French liver reference center. Methods. We performed a retrospective analysis of all patients with confirmed diagnosis of WD, examined in a liver reference center, at the Paul-Brousse Hospital, Villejuif, France. Patients were evaluated clinically, biologically, morphologically and genetically. Hepatic involvement was assessed with liver biopsy and/or liver stiffness measurement. Results. We included in this cohort 107 patients with hepatic symptoms of the WD, 54 (50.5%) females and 53 (49.5%) males, from 1974 to 2016. The mean follow up was 15 years with extremes from 1 to 44 years. Fifty-seven of 107 patients (53.3%) had neurological symptoms (mixed symptoms, neurologic and hepatic) at admission. The mean age at diagnosis of WD was 20.1 (>10.54) years with a difference between the age concerning the ""Hepatic group"" for hepatic symptoms (17<=8.6 years) and the other goup with neurologic symptoms (23>11.4 years) (p=0.0081). Sixty-five patients (70%) had liver pathological analysis and 72 (67%) had liver stiffness measurement. Seventy-three patients (68%) had cirrhosis at diagnosis of the disease. Forty-three patients (76%) had cirrhosis among patients with mixed symptoms (neurologic and hepatic) and 30 (61%) in patients with isolated hepatic symptoms. Thirty-four of 107 patients (32%) were transplanted, at a mean age of 27 (>12.2) years. Among patients who required liver transplantation 18 (52%) had decompensated cirrhosis, 8 (23%) had fulminant liver failure, 8 (23.5%) had severe neurological disease and 5 (14%) had liver cancer. The chelating treatment was very predominantly D Penicillamine, in 104/107 patients. A change in treatment was necessary in 37 (35%) patients because of adverse events to Trientine or Zinc salts. Four patients died in this cohort; two after primary liver cancer (1 HCC and 1 cholangiocarcinoma), one after hemorrhagic stroke and one after liver transplantation for severe neurological symptoms. Conclusion. At presentation of Wilson's Disease, two thirds of patients referred to a reference center of hepatology, had cirrhosis and one-third require liver transplantation. Cirrhosis is diagnosed in 76% patients who have neurological symptoms of the disease. Even if Wilson's Disease can be a severe disease, the prognosis is good for patients in charge in a specialized center.",adult;adverse drug reaction;bile duct carcinoma;brain hemorrhage;cancer prognosis;chelation;clinical assessment;cohort analysis;decompensated liver cirrhosis;diagnosis;female;follow up;France;fulminant hepatic failure;human;liver biopsy;liver cancer;liver stiffness;liver transplantation;major clinical study;male;neurologic disease;prognosis;retrospective study;side effect;Wilson disease;penicillamine;trientine;zinc derivative,"Sobesky, R.;Bello, M. D.;Fernandez, I.;Agostini, H.;Usardi, A.;Adam, R.;Cherqui, D.;Samuel, D.;Gonzales, E.;Jacquemin, E.;Poujois, A.;Woimant, F.;Duclos-Vallee, J. C.",2017,October,,0,1,
1119,Excretion of WTX101 (bis-choline tetrathiomolybdate) after intravenous administration in rat models,"Background Wilson disease (WD) is a rare genetic disorder characterized by toxic free copper (Cu) accumulation. WTX101 (bis-choline tetrathiomolybdate) is an investigational Cu-protein binding agent in development for WD. WTX101 rapidly binds Cu, creating a stable tripartite complex of tetrathiomolybdate, Cu and albumin. We aimed to characterize the routes and rates of excretion of intravenous (IV) WTX101 over 168h post-administration. Methods A single IV dose of WTX101 at either 0.75 or 1.5 mg/kg was administered to Long-Evans Cinnamon (LEC) rats (a model for WD) and Long Evans Agouti (LEA) rats (control strain with normal Cu metabolism). WTX101 was measured as molybdenum (Mo) in urine, feces and selected tissues collected over 168h. Results In the LEC WD rat model, WTX101 was partially excreted at 168h. Up to 45% of the Mo dosed was recovered in excreta: renal clearance accounted for up to 29% of the dose and biliary clearance for around 16%. Mo appeared to be excreted in two phases: a rapid elimination during the first 48h mainly in urine, and slower fecal elimination still ongoing at 168h. In contrast, control LEA rats showed almost full excretion of WTX101 within 168h (87%), mostly through renal clearance during the first 24h (79%). Considering only excreted Mo, the proportion of renal vs fecal excretion was 9:1 in LEA rats, but 6:4 in LEC rats. In both, LEC and LEA rats, Mo in urine corresponded to molybdate, the terminal degradation product of WTX101. Excretion and tissue distribution of Mo was similar for the two WTX101 dose levels. Differences in Mo tissue distribution were only found in LEC vs LEA rats for organs with high Cu content due to the WD phenotype: substantially more tissue Mo was found at 168h in LEC liver (with 1.5 mg/kg: 31.5 vs 5.6% of dose) and kidney (7.6 vs 1.5% of dose) as compared to LEA rats. Conclusion In the WD model, biliary excretion of Mo from WTX101 was enhanced compared to controls, likely reflecting different biotransformation in normal and Cu-overload conditions and consistent with the proposed MoA of WTX101. In LEA controls, there are low Cu amounts available for binding to tetrathiomolybdate, which allows a larger proportion of tetrathiomolybdate to be converted to the terminal degradation product, molybdate, that does not bind Cu and is excreted in urine. In the LEC WD model, excess Cu is bound within a tetrathiomolybdate-Cu-albumin tripartite complex preventing tetrathiomolybdate from converting to molybdate, and resulting in a lower proportion of urinary elimination and a higher proportion of fecal excretion. The different tissue distribution observed between models is also consistent with the WTX101 MoA.",animal experiment;animal model;animal tissue;biliary clearance;biliary excretion;biotransformation;controlled study;copper metabolism;degradation;feces;intravenous drug administration;liver;Long Evans cinnamon rat;nonhuman;phenotype;rat;rat model;renal clearance;tissue distribution;urine;Wilson disease;albumin;choline tetrathiomolybdate;copper;endogenous compound;molybdenum;molybdic acid;tetrathiomolybdic acid,"Plitz, T.;Boyling, L.",2017,October,,0,0,
1120,Decompensated wilson's disease: Advanced hepatic encephalopathy and high bilirubin decide the need for liver transplantation. Does the New Wilson's index help?,"Background: Decision about liver transplant is rather difficult in decompensated Wilson's disease (WD). New Wilson's index (NWI) which was previously considered helpful, has now conflicting reports about it's efficacy in predicting outcome of WD. Methods: Of the 85 cases of WD, 74 were either acute on chronic liver failure (ACLF) or decompensated CLD (DCLD). They were managed with supportive care along with combination of d-pencillamine and zinc salt. Univariate and multivariate analysis was done to see the association of the risk factors with poor outcome (liver transplantation or death) anytime during hospital stay. Results: Of the total 74, 46 (62.2%) improved on medical management and 28 (37.8%) either died (21) or were transplanted (7) within 3 months of the diagnosis. Jaundice was the presenting symptom in 100% cases of ACLF and 13 (33.3%) of the DCLD. Hepatic encephalopathy (HE) was present in 52 (70.3%) of 74 decompensated cases (ACLF or DCLD) : 29 cases had HE grade 1/2 and 23 had HE grade 3/4. HE grade 3/4 was present in 19/35 (54.2%) of ACLF and 4/39 (10.2%)of DCLD and the difference was significant (OR 10.39 95% CI 3.03-35.5, p=0.00). Among those with poor outcome, significantly (OR 3.07, 95% CI 1.15-8.16, p=0.0031) higher proportions of ACLF (18 of 35, 51.4%) than DCLD (10 of 39, 25.6%)were present. Among those with New Wilson's Index (NWI)>11 (33/74 cases) 12 survived and 21 had poor outcome.Among the 28 with poor outcome 20 had HE grade 3/4. On comparison with univariate analysis of clinical and biochemical parameters to identify the risk factors for poor outcome, HE grade 3/4 (OR 35.8 95% CI 8.58-149, p=0.00), bilirubin >20 mg/dl (OR 14.3, 95% CI 3.58-57.2, p= 0.000), ACLF as presentation (OR 3.07, 95% CI 1.15-8.16, p=0.031), AST (Mean difference 160.8, 95% CI 64.8-256, p=0.001), INR (Mean difference 1.63, 95% CI 0.93-2.33, p=0.000), NWI (Mean difference 5.37, 95% CI 3.67-7.08, p=0.00) and PELD/MELD score (Mean difference 11.47, 95% CI 6.7-16.2, p=0.00), were significantly associated with poor outcome (table 1). The LRA model (HE grade 3/4, Bilirubin >20 mg/dl or HD score, NWI or INR or PELD) improved from 62.2% to 86.5% before and after the model was introduced. On LRA significant association with poor outcome was seen only with HE grade 3/4 (adjusted OR 37.8, 95% CI 7.68-186.49 p= 0.000) and bilirubin >20 mg/dl (adjusted OR15.5, 95% CI 2.7-86.8p=0.002). Conclusion: HE grade 3/4 and high bilirubin (>20 mg/dl) are independently associated with need for liver transplant in decompensated WD. NWI did not show significant independent association with need for liver transplant.",acute on chronic liver failure;animal model;death;diagnosis;disease course;hepatic encephalopathy;hospitalization;human;international normalized ratio;jaundice;liver graft;major clinical study;Model For End Stage Liver Disease Score;multivariate analysis;risk factor;univariate analysis;Wilson disease;bilirubin,"Alam, S.;Sood, V.;Khanna, R.;Lal, B. B.;Pawaria, A.",2017,October,,0,0,
1121,Epigenetic regulation of thioredoxin system in an animal model and in patients with wilson disease,"Background: Wilson disease (WD) is a genetic disorder caused by mutations in the copper transporter, ATP7B, leading to copper accumulation in the liver and brain. Excess copper has been shown to cause oxidative stress and impair DNA methylation. We hypothesized that dietary supplementation with the methyl donor, choline, alone or combined with the copper chelator, penicillamine (PCA), will alter hepatic expression of genes relevant to the oxidative stress response pathway known as the thioredoxin system in the Jackson toxic milk (tx-j) mouse model of WD. Furthermore, we studied the whole blood DNA methylation profile in healthy and WD patients. Methods: Fetal mouse liver: wild-type and tx-j dams consumed normal or high choline diet 2 weeks prior to gestation until embryonic day 17, at which time fetal livers were collected. Adult tx-j progeny liver: mice were randomized to 1 of 6 treatment groups: 1) normal choline in dam and progeny; 2) high choline in dam, normal choline in progeny; 3) high choline in dam and progeny; 4) normal choline in dam, normal choline in progeny+PCA; 5) high choline in dam, normal choline in progeny+PCA; 6) high choline in dam, high choline in progeny+PCA. Livers were collected at 24 weeks of age. Humans: DNA isolated from whole blood of 10 healthy (9M/1F) and 10 WD patients (9M/1F) was bisulfite converted and used to prepare Methyl-Seq libraries for sequencing on an Illumina 2500 HiSeq. Samples were matched by age, sex, BMI, and ethnicity, and all WD samples harbored the H1069Q mutation in the ATP7B gene. Results: Fetal hepatic transcript levels of the oxidative stress-related genes, thioredoxin 1 (Txn1) and peroxiredoxin 1 (Prdx1), were lower in fetal livers from tx-j mice compared to wild-type, and normalized in tx-j livers after maternal choline supplementation. In 24-week old progeny, hepatic transcript levels of Txn1 and Prdx1 were significantly higher (10-46% and 17-41%, respectively) in males and females receiving maternal and continued choline compared to all other treatment groups. PCA-treated males and females that did not receive choline after weaning had lower levels of Txn1 (23-31%) compared to untreated tx-j mice. Txn1 hepatic protein expression displayed the same pattern as Txn1 gene expression. Of the 40 Txn-related genes surveyed in human blood, 5 genes displayed hypermethylation (7-28%) and 2 genes displayed hypomethylation (5-6%) in WD patients compared to healthy controls. Conclusion: Maternal and continued choline supplementation impacts Txn1 hepatic transcript and protein levels in tx-j mice, and patients with WD exhibit altered blood DNA methylation profiles of genes related to the Txn system.",adult;animal experiment;animal model;animal tissue;blood;body mass;controlled study;diet supplementation;DNA methylation;epigenetics;ethnicity;female;fetus;fetus liver;gene mutation;genetic transcription;library;male;milk;mouse;mouse model;nonhuman;oxidative stress;pregnancy;progeny;protein expression;weaning;wild type;Wilson disease;bisulfite;choline;endogenous compound;liver protein;penicillamine;peroxiredoxin 1;thioredoxin;thioredoxin 1;Wilson disease protein,"Kieffer, D. A.;Mordaunt, C.;Shibata, N.;Czlonkowska, A.;Litwin, T.;Weiss, K. H.;LaSalle, J. M.;Medici, V.",2017,October,,0,0,
1122,An ongoing extension of a phase 2 study of wtx101 in newly diagnosed wilson disease patients,"Background: WTX101 (bis-choline tetrathiomolybdate) is a first-in-class copper-protein-binding agent that reduces plasma non-ceruloplasmin bound copper (NCC) by forming tripartite complexes with albumin, and increases biliary copper excretion. In a Phase 2 study, oral once-daily WTX101 rapidly lowered and controlled NCC, improved disability and neurologic status, and stabilized liver function in newly diagnosed patients with Wilson Disease (WD) after 24 weeks. Here, we present preliminary 24 to 48-week data from the ongoing extension period. Methods: All 22 patients who completed the 24-week open-label, single-arm, Phase 2 study opted to continue WTX101 treatment, with once-daily response-guided individual dosing. The key parameters reviewed from 24 to 48 weeks were change in NCC levels corrected for copper in tripartite tetrathiomolybdate-copper-albumin complexes (NCCcorrected), hepatic status, neurologic and disability scores using the Unified Wilson Disease Rating Scale (UWDRS), and safety. Results: Patients (aged 18 to 64 years, 45% male, 86% with various degree of neurologic symptoms and around 50% with cirrhosis at study entry) received WTX101 at a dose of 7.5 to 60 mg/day once daily, with most patients receiving 30 mg/day. Between 24 and 48 weeks, mean NCCcorrected remained controlled (0.9 muM at week 24 and 0.5 muM at week 48). Mean international normalized ratio, albumin and alanine aminotransferase (ALT) levels, and Model for End-Stage Liver Disease (MELD) score improved or remained unchanged at week 48 compared to week 24, indicating stability of liver function. Reversible ALT elevations, observed in about 1/3 of patients prior to week 24, were not observed in the extension period. Patients showed continued improvements in mean UWDRS disability score (2.2 vs 4.1) and neurologic score (12.5 vs 16.6) at week 48 vs week 24. WTX101 was generally well tolerated. Neutropenia, observed in one patient at week 36, normalized with dose reduction. One patient discontinued treatment due to her wish to conceive. One patient with a progressive disease course experienced neuropsychiatric deterioration despite ongoing treatment. Conclusions: WTX101 appears well tolerated in patients with WD beyond 24 weeks of treatment. Initial improvements in free copper levels, and hepatic and neurologic status were preserved or further improved with WTX101, suggesting WTX101 may be an effective maintenance therapy for WD. These findings, together with its simple dosing regimen, indicate that WTX101 has the potential to address several unmet needs in the treatment of WD.",adult;clinical trial;deterioration;diagnosis;disability;female;gene expression;human;international normalized ratio;liver cirrhosis;liver function;maintenance therapy;major clinical study;male;Model For End Stage Liver Disease Score;neurologic disease;neutropenia;phase 2 clinical trial;rating scale;Wilson disease;alanine aminotransferase;albumin;endogenous compound,"Schilsky, M. L.;Askari, F. K.;Ferenci, P.;Ala, A.;Czlonkowska, A.;Nicholl, D. J.;Bronstein, J.;Bega, D.;Weiss, K. H.",2017,October,,0,0,
1123,Treatment of elastosis perforans serpiginosa using a fractional carbon dioxide laser,,adult;application site discomfort/co [Complication];article;case report;clinical article;clinical effectiveness;edema/co [Complication];elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/th [Therapy];erythema/co [Complication];female;human;hyperkeratosis/si [Side Effect];hyperkeratosis/th [Therapy];low level laser therapy;pain/co [Complication];priority journal;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];carbon dioxide laser/am [Adverse Device Effect];Fraxel Repair,"Kelati, A.;Lagrange, S.;Le Duff, F.;Lacour, J. P.;Passeron, T.",2017,October,http://dx.doi.org/10.1001/jamadermatol.2017.2223,0,0,
1124,"Wilson Disease: Diagnosis, Treatment, and Follow-up","Consideration of a diagnosis of Wilson disease is still the critical factor in testing for and establishing disease diagnosis. In association with other clinical and biochemical tests, liver biopsy results and molecular genetic testing can also be used to generate a score for diagnosing Wilson disease. Medical therapy is effective for most patients; liver transplant can rescue those with acute liver failure or those with advanced liver disease who fail to respond to or discontinue medical therapy. Treatment monitoring must be done at regular intervals and includes clinical evaluation, liver tests and blood counts, and copper metabolic parameters. Copyright © 2017 Elsevier Inc.",Ceruloplasmin;Copper;Liver failure;Wilson disease;blood cell count;brain radiography;ceruloplasmin blood level;chelation therapy;clinical evaluation;colitis/si [Side Effect];copper blood level;copper metabolism;drug hypersensitivity;dyspepsia/si [Side Effect];family assessment;follow up;genetic screening;human;hypersensitivity/si [Side Effect];incidence;liver biopsy;liver examination;liver transplantation;lupus like syndrome/si [Side Effect];myasthenia/si [Side Effect];nephritis/si [Side Effect];nonhuman;nuclear magnetic resonance imaging;pathogenesis;patient compliance;patient monitoring;review;scoring system;treatment duration;treatment withdrawal;urinalysis;vitamin supplementation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];wtx 101,"Schilsky, M. L.",2017,November,http://dx.doi.org/10.1016/j.cld.2017.06.011,0,0,
1125,Unusual onset of de-novo neurologic disturbances in wilsonian siblings after orthotopic liver transplantation: A case report of three sisters,"Background: Wilson's Disease (WD) is an autosomal disorder of copper metabolism which results in progressive liver cirrhosis, neurologic impairment, and renal malfunction. Although WD is rare in number, it accounts for 6%-20% of emergency Liver Transplantations (LT) due to its rapid deterioration. This study is to present two of three sisters with WD who developed severe neurologic complications after orthotopic liver transplant. Case Presentation: Three 28, 25, and 19-year-old sisters who were known cases of WD cirrhosis and normal neurologic status underwent LT from deceased donors. While the first and third sisters developed severe new-onset neurologic disabilities 6 and 8 months after transplantation respectively, the second sibling showed no symptoms. Pre-transplant magnetic resonance imaging of brain revealed hyperintensity in the bilateral basal ganglia particularly in the caudate nucleus, putamen, and globus pallidus in T2 and fluid-attenuated inversion recovery sequences for both involved patients. Ceruloplasmin, copper, and 24 h urinary copper excretion at diagnosis were 13 and 12.9 (mg/dl), 26 and 32 (lg/dl), and 9 and 21.8 (lg) for the first and third sisters, respectively. Post-transplant neurologic findings were ataxia, dysarthria, dysphagia, sialorrhea, and tremor. In addition, unilateral blepharoptosis was observed in the youngest sister. Continuous administration of a chelating agent (mainly zinc sulfate) was considered against copper toxicity. Neurologic symptoms improved significantly 6-8 months after transplantation. Conclusion: Although published literatures indicate that better pre-transplant conditions appeared to be advantageous in gaining better outcomes of patients with WD, but close monitoring of neurologic symptoms remains as an important area during the long-term post-transplant course. Furthermore, as new-onset neurologic disabilities in WD following LT are not expected, this phenomenon needs to be more studied in these siblings.",adult;animal model;ataxia;case report;caudate nucleus;diagnosis;dysarthria;dysphagia;excretion;female;globus pallidus;human;human tissue;hypersalivation;liquid;liver cirrhosis;liver graft;monitoring;neurological complication;nuclear magnetic resonance imaging;ptosis;putamen;remission;sister;toxicity;tremor;Wilson disease;young adult;ceruloplasmin;chelating agent;endogenous compound;zinc sulfate,"Aliakbarian, M.;Rezayat, K. A.;Hosseini, M.;Tohidinezhad, F.",2017,September,http://dx.doi.org/10.1111/tri.13050,0,0,
1126,Hepatolenticular degeneration: Report of three cases. [Spanish],"Hepatolenticular degeneration (Wilson disease) is a rare inherited disease that usually affects the liver, but may present in different forms and have multiple systemic complications. Diagnosis requires a high index of suspicion, mainly in young patients, and to take into account the main risk groups. Opportune and adequate treatment is important to avoid complications. We present three cases of this disease occurring in a family from Granada (Antioquia, Colombia), and treated at a III level institution in Cali (Colombia). The index case debuted with neuropsychiatric disorder, the second one was diagnosed on the basis of the family history and the third one started with steatohepatitis. The diagnostic score proposed by the Eighth Meeting on Wilson's disease was 3 in two of the patients, and 4 in the third one. They were treated with D-penicillamine and monitored for 5 years, with minimal adverse events and no evidence of disease progression. Copyright © 2017, Universidad de Antioquia. All rights reserved.",Hepatolenticular Degeneration;Penicillamine;article;disease course;experimental steatohepatitis;family history;human;mental disease;nonalcoholic fatty liver;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Castano, O.;Gomez, D. M.;Ocampo-Chaparro, J. M.;Casanova, M. E.",2017,October-December,http://dx.doi.org/10.17533/udea.iatreia.v30n4a07,0,0,
1127,Hereditary Multiple Cerebral Cavernous Malformations Associated with Wilson Disease and Multiple Lipomatosis,"We report on a patient with 2 Mendelian diseases-symptomatic multiple familial cerebral cavernous malformations (FCCMs) and Wilson disease. Genetic analysis revealed single nucleotide polymorphisms in genes CCM2 and CCM3, associated with cavernous malformations, and homozygote mutation in the ATP7B gene, responsible for Wilson disease. FCCMs were symptomatic in 3 generations. The patient also had multiple lipomatosis, which is suggested to be a familial syndrome. In recent years there has been an increasing amount of publications linking FCCMs with other pathology, predominantly with extracranial and intracranial mesenchymal anomalies. The present study is the description of an unusual association between 2 independent hereditary diseases of confirmed genetic origin-a combination that has not been described previously. Copyright © 2017 Elsevier Inc.",Comorbidity;Genetics;Hereditary cerebral cavernous malformations;Multiple subcutaneous lipomatosis;Wilson disease;albumin blood level;anemia;article;ascites;ataxic gait;blood sampling;body weight;case report;cavernous hemangioma;CCM2 gene;CCM3 gene;ceruloplasmin blood level;computer assisted tomography;disease association;disease severity;enzyme activity;eye examination;family history;fatigue;female;follow up;gaze paralysis;gene;genetic analysis;headache;hemoglobin blood level;hepatomegaly;homozygote;human;human tissue;hydrocephalus;hyperbilirubinemia;jaundice;leg edema;lifestyle;lipomatosis;liver biopsy;liver cirrhosis;liver function test;medical history;nerve paralysis;neurologic examination;nuclear magnetic resonance imaging;obstructive hydrocephalus;partial blindness;postoperative period;remission;seizure;single nucleotide polymorphism;social behavior;speech disorder;third ventriculostomy;thrombocytopenia;unsteadiness;visual impairment;whole genome sequencing;alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin;gamma glutamyltransferase/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine,"Belousova, O. B.;Okishev, D. N.;Ignatova, T. M.;Balashova, M. S.;Boulygina, E. S.",2017,September,http://dx.doi.org/10.1016/j.wneu.2017.06.002,0,0,
1128,Auxiliary partial orthotopic living liver transplant for wilson disease,"Wilson disease is a genetic disease involving copper metabolism disturbances that result in copper accumulations, especially in the liver and brain. Wilson disease can be treated with pharmacologic agents, such as chelators that induce urinary excretion of copper or zinc salts that inhibit copper absorption in the digestive tract. Liver transplant is the only treatment option for Wilson disease when liver failure has occurred. In some patients, that is, in those with Child-Pugh A score, neurologic disease can be seen without hepatic failure. Our recommendation is for these patients to have auxiliary partial orthotopic liver transplant. Here, we present a 36-year-old male patient with neurologic disease associated with Wilson disease who had successful related living-donor auxiliary partial orthotopic liver transplant using a left lobe. The patient, as a result of neurologic symptoms that included tremor walking and speaking problems and low serum ceruloplasmin level of 7 mg/dL, was diagnosed with Wilson disease, and a liver biopsy was performed. Chronic necroinflammatory disease activity was 4/18, and the patient received chelation treatment. His hepatic functions were normal. The donor was the patient's 57-year-old father whose liver function tests were also normal. The graft-to-recipient weight ratio was 1% using a left lobe graft. After transplant, serum ceruloplasmin levels on day 15 and month 1 were 14 and 19 mg/dL. At month 1, liver function tests were normal. Doppler ultrasonography showed normal vascular flow of the native liver and the graft. The patient's neurologic symptoms were progressively reduced. Progressive neurologic deterioration with no hepatic insufficiency is considered a suitable indication for auxiliary partial orthotopic liver transplant; this procedure is suggested before the neurologic and liver failure symptoms of Wilson disease occur. Copyright © Baskent University 2017 Printed in Turkey. All Rights Reserved.",Child-Pugh score;Neurologic disease;Progressive neurological deterioration;adult;anthropometric parameters;article;bile duct bypass;bilirubin blood level;case report;ceruloplasmin blood level;Doppler ultrasonography;end to end anastomosis;end to side anastomosis;endoscopic retrograde cholangiopancreatography;endoscopic sphincterotomy;graft to recipient weight ratio;human;human tissue;liver biopsy;liver resection;liver transplantation;living donor;male;tremor;walking difficulty;Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound],"Haberal, M.;Akdur, A.;Moray, G.;Boyacioglu, S.;Torgay, A.;Arslan, G.;Ozdemir, B. H.",2017,February,http://dx.doi.org/10.6002/ect.mesot2016.P64,0,0,
1129,,"We report a case of hepatocellular carcinoma developed in a 58-year-old man whose Wilson's disease (WD) was diagnosed at the age of 12 years. The patient was treated with D-penicillamine for over 40 years. Contrastenhanced CT and MRI revealed two nodules in liver segment 4 (S4) and 8 (S8). The nodule in S8 was confirmed as moderately differentiated hepatocellular carcinoma by targeted liver biopsy. Biopsy specimen from nontumorous area showed mild fibrosis but the liver was not cirrhotic. Rhodanine stain and Berlin blue stain showed copper and iron accumulation in hepatocytes. Hepatocellular carcinoma was successfully treated with transcatheter arterial chemoembolization and radiofrequency ablation. Development of liver cancer in WD patients is regarded as scarce, especially in non-cirrhotic cases. Herein we discuss hepatic iron accumulation and possible contribution of iron to hepatocarcinogenesis in WD. Copyright © 2017 The Japan Society of Hepatology.",Ceruloplasmin iron;D-penicillamine;Hepatocellular carcinoma;Wilson's disease;adult;case report;chemoembolization;diagnosis;fibrosis;human;human tissue;liver biopsy;liver carcinogenesis;liver cell carcinoma;liver nodule;male;middle aged;nuclear magnetic resonance imaging;radiofrequency ablation;stain;ceruloplasmin;ferric ferrocyanide;iron;penicillamine;rhodanine,"Fukutomi, K.;Sakamori, R.;Furuta, K.;Shigekawa, M.;Yamada, R.;Kodama, T.;Hikita, H.;Yakushijin, T.;Tatsumi, T.;Honma, K.;Morii, E.;Takehara, T.",2017,,http://dx.doi.org/10.2957/kanzo.58.519,0,0,
1130,Was Cavum Septum Pellucidum the Cause of Intractable Seizure in a 17-Year-Old Boy with Wilson Disease?,"Background Cavum septum pellucidum (CSP), which is often found incidentally in a few populations, occasionally becomes symptomatic if enlarged significantly. Wilson disease (WD) is an uncommon autosomal recessive inborn defect in copper metabolism characterized by abnormal accumulation of copper in various tissues, particularly in the liver and the brain. Seizure disorder, although rare both in CSP and WD, may happen in a few patients with either of the conditions. Case Description We report a case of 17-year-old boy, a patient with known WD, who developed intractable seizure for a year, which was not controlled with a large amount of antiepileptics. Magnetic resonance imaging showed enlargement of his preexisting CSP, which was small and asymptomatic at the time of diagnosis of WD. His WD was in a state of remission when he developed the seizure disorder. On endoscopic cyst fenestration, he was relieved of the seizure. Conclusions Symptomatic CSP is a rare disorder, but the coexistence of WD is even rarer. Endoscopic cyst fenestration is a novel procedure that can be successful in properly selected cases. To the best of our knowledge, CSP associated with WD has not been reported in any English literature. We present this case for its rarity along with a relevant literature review. Copyright © 2017 Elsevier Inc.",Cavum septum pellucidum;Endoscopic cyst fenestration;Seizure;Wilson disease;add on therapy;adolescent;anticonvulsant therapy;article;brain disease;case report;cognitive defect;electroencephalography;follow up;human;intractable epilepsy/dt [Drug Therapy];male;medical history;nuclear magnetic resonance imaging;postoperative period;remission;septum pellucidum;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenytoin;valproic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Rahman, A.;Haque, S. U.;Bhandari, P. B.;Alam, S.",2017,September,http://dx.doi.org/10.1016/j.wneu.2017.06.032,0,0,
1131,Cholangiocarcinoma in wilson's disease - A case report,"It has been suggested that hepatobiliary carcinomas are less frequent in Wilson's disease (WD) than in liver diseases of other etiology. However, the protective role of copper against malignancies is debated. Only a few cases of cholangiocarcinoma (CCC) in WD have been published. Here we report on a case of a 47-year-old male H1069Q homozygous, Kayser-Fleischer ring positive WD patient with a low ceruloplasmin level who was followed up and treated with chelating agents throughout nine years. The patient presented with neurological symptoms and liver cirrhosis at diagnosis. Clinical symptoms regressed after the treatment initiation. Rapidly developed tumour metastases were found in the bones, lung and liver (without jaundice). Autopsy revealed cholangiocarcinoma as the primary tumour confirmed by strong CK7 positivity and glypican-3 negativity. The curiosity of the presented case is the very rapid development of CCC despite continuous chelating agent therapy. Copyright © 2017, Romanian Society of Gastroenterology. All rights reserved.",Cholangiocarcinoma;Copper chelating agents;Hepatolenticular degeneration;Liver cirrhosis;Wilson's disease;adenocarcinoma;adult;article;ATP7B gene;backache;bile duct carcinoma;blood cell count;bone atrophy;case report;ceruloplasmin blood level;clinical article;computer assisted tomography;depression;dysarthria;dystonia;fine needle aspiration biopsy;gene;gene mutation;hand tremor;histology;human;human tissue;immunohistochemistry;laboratory test;liver function test;male;mental disease;middle aged;motor dysfunction;neurologic disease;thrombocytopenia;ultrasound;Wilson disease;alkaline phosphatase;aminotransferase/ec [Endogenous Compound];C reactive protein/ec [Endogenous Compound];cytokeratin 7/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];glypican 3;penicillamine;tumor marker,"Nemeth, D.;Folhoffer, A.;Smuk, G.;Kajtar, B.;Tornoczky, T.;Szalay, F.",2017,September,http://dx.doi.org/10.15403/jgld.2014.1121.263.nem,0,0,
1132,Zinc monotherapy for young children with asymptomatic wilson disease: Multicenter study in japan,"Background and Aims: AASLD and EASL guidelines recommend zinc monotherapy as a treatment for asymptmoatic patients with Wilson disease (WD). However, there are a few reports of zinc monotherapy for young children with asymptomatic WD. Here, we aimed at evaluating long-term efficacy and safety of zinc monotherapy for young children, under 10 years old, with asymptomatic WD in Japanese pediatric centers and establishing appropriate benchmarks of maintenance therapy. Methods: We performed a retro- and prospective study to examine 21 children (median age 6 years, range 1-9) who satisfied diagnostic criteria for WD and were treated solely with zinc acetate prior to symptom onset at 10 participating pediatric centers in Japan. No additional WD sequelas, such as jaundice, hepatomegaly, or neurologic abnormalities were noted. We monitored serum AST and ALT, nonceruloplasmin serum copper, and 24-hour urinary copper for 1-7 years after initiation of zinc monotherapy. We performed abdominal ultrasonograpy and evaluated clinical WD manifestations, drug compliance, and adverse effects of zinc. The prescribed dosage of zinc acetate for patient <= 5 years was 25 mg twice daily; for those children 6 years or older, the dose was 25 mg 3 times daily. We increased the dosage of zinc if the patients had AST/ALT > 50-70 U/L, and decreased it if they had adverse effects of zinc such as iron-deficiency anemia or pancytopenia. Results: At time of diagnosis, AST/ALT and 24-hour urinary copper were 148+/-118/234+/-151 U/L and 124+/-54 mug/day (5.8+/-2.9 mug/kg/day), respectively. All patients continued to take zinc without any evidence of zinc toxicity. None of our 21 patients became clinically symptomatic. AST/ALT significantly decreased to 54+/-30/77+/-49 U/L (P<0.001) at 1 month after initiation of treatment and was mostly maintained under 50 U/L for 1-7 years (AST/ALT: 33+/-7/38+/-17 and 29+/-5/34+/-6 U/L at 1 and 7 years after initiation of treatment, respectively). Twenty four-hour urinary copper significantly decreased to 49+/-21 mug/day (2.2+/-1.1 mug/kg/day; P<0.001) at 6 months after initiation of treatment and was mostly maintained under 75 mug/day and between 1 and 3 mug/kg/day for the remainder of the study (2.2+/-0.6 and 1.5+/-0.2 mug/kg/day at 1 and 7 years after initiation of treatment, respectively). Conclusions: Long-term zinc monotherapy for young children with asymptomatic WD proved highly effective and safe. A reasonable goal in treating young children with asymptomatic WD using zinc appears to be maintaining both AST/ALT under 50 U/L and 24-hour urinary copper excretion between 1 and 3 mug/kg/day (and under 75 mug/day).",adverse drug reaction;child;clinical article;clinical trial;comparative effectiveness;congenital malformation;controlled clinical trial;controlled study;copper blood level;diagnosis;drug therapy;excretion;hepatomegaly;human;human tissue;iron deficiency anemia;Japan;jaundice;maintenance therapy;medication compliance;monotherapy;multicenter study;nervous system;pancytopenia;pediatric hospital;pharmacokinetics;preschool child;prospective study;safety;school child;side effect;symptom;toxicity;Wilson disease;zinc;zinc acetate,"Mizuochi, T.;Eda, K.;Takaki, Y.;Iwama, I.;Araki, M.;Inui, A.;Hara, S.;Kumagai, H.;Hagiwara, S. I.;Murayama, K.;Murakami, J.;Kodama, H.",2016,October,,0,0,
1133,Liver transplantation in severe neurological forms of Wilson disease; a multicentric French experience,"Introduction. The standard treatment of Wilson disease (WD) is chelating copper agent or zinc salts. Liver transplantation (LT) is indicated in cases of immediate severe liver failure or severe worsening under treatment. The indication of LT in neurological forms without liver decompensation remains controversial. Aim. The aim of this study was to evaluate the benefit of LT in WD with severe neurological symptoms without decompensated liver function. Methods. This is a retrospective study. From 2002 to 2015, seventeen patients underwent a LT in France for severe neurological complications of WD without improvement despite medical treatment, without liver failure. All patients received chelating copper and 4 patients received chelating copper with zinc salts. Twelve patients presented a worsening after diagnosis of WD and 5 patients after a treatment interruption without improvement after a well-conducted treatment. Assessment of the severity of the disease was done with the Unified WD Rating Scale (UWDRS) before and after LT. Results. Main neurological symptoms combined dystonic postures (15/17), parkinsonian syndrome (9/17) and tremor (3/17). Mean age at diagnosis of WD was 17.9 [6-39] years and the interval time between worsening and LT was 12.6 [3-24] months. Mean age at LT was 20.2 [11-41] years. For all patients, an emergency procedure was needed to access to the transplantation. All patients had cirrhosis after analysis of the native liver. The CHILD score was A for all patients at the time of transplantation. The mean follow-up time after transplant was 51.8 [3-156] months. Survival was 84%, 75% and 66% at 1, 2 and 5 years respectively. For patients died after LT from severe sepsis, after an interval of 16 [1.5-36]. All of these 4 patients had a severe sepsis with a stay in intensive care unit before LT. Twelve (70%) needed a nutritional support (gastrostomy or jejunostomy) and 9 (53%) a tracheotomy in a context of swallowing disorders. All of patients alive presented an improvement after LT. The mean percentage of improvement of UWDRS was 61.2% (+/-22.2). According to the percentage of improvement 6 patients (35%) presented a major improvement (>70%), 5 patients a moderate improvement (30% to 70%) and 2 (12%) a mild improvement (<30%). Conclusion. Liver transplantation is an effective treatment option in Wilson disease for patients with worsening neurological symptoms despite medical treatment, even in the absence of liver failure. Patients with unfavorable evolution died of severe sepsis. A long history of fixed neurological symptoms and previous severe sepsis represent pejorative factors.",adolescent;adult;body posture;chelation;child;clinical article;clinical trial;controlled study;decompensated liver cirrhosis;diagnosis;dysphagia;dystonia;emergency;follow up;France;gastrostomy;human;human tissue;intensive care unit;jejunostomy;liver failure;liver function;liver transplantation;neurological complication;nutritional support;parkinsonism;rating scale;retrospective study;sepsis;tracheostomy;treatment interruption;tremor;Wilson disease;zinc derivative,"Sobesky, R.;Poujois, A.;Brunet, A. S.;Broussolle, E.;Guillaud, O.;Salame, E.;Maillot, F.;Vanlemmens, C.;Hermeziu, B.;Meissner, W.;De Ledinghen, V.;Adam, R.;Cherqui, D.;Castaing, D. X.;Samuel, D.;Woimant, F.;Duclos-Vallee, J. C.",2016,October,,0,1,
1134,Copper and molybdate metabolism in newly diagnosed Wilson disease patients treated with WTX101,"Background and aims WTX101 (bis-choline tetrathiomolybdate) is an investigational drug with a novel copper binding mechanism. WTX101 has a favorable stability profile. The aim of this study is to determine the effect of WTX101 on parameters of copper and molybdenum metabolism in this phase 2 trial. Methods 28 newly diagnosed adult patients with WD copper and molybdenum parameters in blood and urine were followed during treatment with WTX101. Results Urinary molybdenum excretion was robust, reaching on average 20%- 25% of the administered dose as early as 4 weeks after treatment initiation, 24h molybdenum excretion ranging from 10 - 20 mmoles. This demonstrated good drug absorption. Urinary molybdenum excretion as percent WTX101 dosage was the same for 15 and 30 mg/d, but less for 60 mg/d dosing, suggesting possible saturation of absorption at doses > 30 mg/d. Molybdenum in urine was excreted in form of molybdate, the terminal degradation product of tetrathiomolybdate. 24h urine copper averaged ~ 4 mmoles or 254 mg prior to treatment and was reduced by week 12 and week 24. Total plasma Cu levels increased upon initiation of treatment, based on tetrathiomolybdate redistributing hepatic Cu stores into the blood forming a tripartite tetrathiomolybdate-Cu-albumin complex. Levels decreased over time. Total plasma Cu levels closely followed total molybdenum in plasma, compatible with tripartite complex formation. At steady state, the vast majority of molybdenum in plasma was part of a tripartite complex, with trace free molybdate not bound to Cu. A correction factor was calculated for the ratio of Cu redistributed to the blood compartment per mole of Mo, allowing determination of free copper. Free Cu assessed as non-ceruloplasmin Cu (NCC) adjusted for molybdenum decreased over time. Summary WTX101 administration was accompanied by a robust urinary molybdate excretion demonstrating good drug absorption. Urine copper excretion decreased over time in parallel with decreases in free plasma copper, NCC molybdenum corrected. Total plasma Cu levels followed total plasma molybdenum, reflecting redistribution of hepatic Cu and formation of tripartite complex in blood. Conclusion WTX101 redistributes hepatic Cu into blood in form of a tetrathiomolybdate-Cu-albumin tripartite complex. Drug not binding Cu is excreted in urine as molybdate. Urine copper excretion parallels improvement in copper metabolism and may be a useful marker to follow in WD patients treated with WTX101. WTX101 is a novel agent for treating WD, and a further understanding of the relationship between molybdate and copper metabolism is important for optimizing treatment and monitoring.",clinical article;clinical trial;complex formation;controlled study;copper blood level;copper metabolism;degradation;diagnosis;drug absorption;drug therapy;excretion;human;human tissue;monitoring;steady state;urine;Wilson disease;albumin;endogenous compound;molybdenum;molybdic acid;tetrathiomolybdic acid,"Askari, F. K.;Schilsky, M. L.;Ferenci, P.;Ala, A.;Czlonkowska, A.;Nicholl, D. J.;Bronstein, J.;Bega, D.;Weiss, K. H.",2016,October,,0,0,
1135,Wilson disease: Sex-specific changes in methionine metabolism and mitochondrial function in a mouse model,"Background & Aims. Women with Wilson disease (WD) present more frequently with acute liver failure than men, whereas men present with neurological involvement more frequently than women. While these findings have been attributed to hormonal factors, the gender differences could be related to epigenetic mechanisms and their relationships with mitochondrial function. The goal of the present study was to determine whether parameters of methionine metabolism and mitochondrial function are different by gender in an animal model of WD. Methods. Tx-j mice, a model of WD, (n=9 males; n=8 females) were euthanized at 24 weeks of age to study differences in transcript levels of genes related to methionine metabolism and oxidative phosphorylation. Targeted metabolomic analysis by LC-MS was conducted in plasma samples to compare acylcarnitine profiles. An additional group (n=4 males; n=4 females) was treated with oral D-penicillamine (PCA) from 12 to 24 weeks to compare sex-related responses to copper chelation. Results. Males presented worse hepatic inflammation than females (1.6 +/- 0.6 vs 0.9 +/- 0.32; p<0.05), steatosis was similar and mild and there was no fibrosis. Liver S-adenosylmethionine (SAM) levels were lower and S-adenosylhomocysteine were higher in males with consequent lower SAM-to-SAH ratio (2.2+/-0.7 vs 2.8+/-1; p<0.05), an indicator of global DNA methylation potential. Transcript levels of DNA methyltransferases 1 (Dnmt1) were higher in females and of Ndufab1 and Atp5j, related to mitochondrial complex I and complex V respectively, were lower in males. Metabolomic analysis revealed higher unsaturated acylcarnitine 14:2 and saturated acylcarnitine 12:0 in females compared to males. PCA reduced hepatic copper levels by one half in males but was ineffective in females. Histologic response to PCA was similar in both sexes, and there were no changes in SAM and SAH levels in response to PCA. Among females, Dnmt1 transcript levels were significantly down-regulated after PCA, in association with higher levels of 10- acylcarnitine indicating overall less improvement of mitochondrial function. Conclusions. Males and female mice models of WD differ according to parameters of methionine metabolism, mitochondrial function, and in response to copper chelation treatment. These data provide insights into the gender differences observed in patients with WD and indicate the need to adjust chelation treatment according to gender differences.",animal experiment;animal model;animal tissue;chelation;controlled study;disease model;DNA methylation;DNA transcription;female;fibrosis;gene expression regulation;inflammation;liver;male;mitochondrion;mouse;mouse model;nonhuman;oxidative phosphorylation;plasma;sex difference;steatosis;transcription regulation;Wilson disease;acylcarnitine;DNA methyltransferase;DNA methyltransferase 1;endogenous compound;methionine;penicillamine;proton transporting adenosine triphosphate synthase;reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone);s adenosylhomocysteine;s adenosylmethionine,"Medici, V.;Shibata, N.;Kharbanda, K. K.;Kim, K.;Halsted, C. H.",2016,October,,0,0,
1136,"An ongoing phase 2, multi-center, open-label, study of WTX101 in newly diagnosed wilson disease patients","Background and aims WTX101 (bis-choline tetrathiomolybdate) is an investigational drug with a novel copper binding mechanism, which is tested in an ongoing prospective study to evaluate the safety and efficacy in newly diagnosed Wilson Disease (WD) patients. Methods Patients with a confirmed diagnosis of WD aged > 18 years and naive to treatment or treated for <= 2 years with chelation or zinc therapy initially received 15 or 30 mg WTX101 QD, and after 6 weeks, dosage was guided by laboratory and clinical criteria. Regular assessments included safety, status of liver disease, neurological status using the Unified Wilson Disease Rating Scale (UWDRS), and parameters of copper metabolism. Results Twenty-eight patients have been enrolled in the study. On trial entry, most patients were untreated or treated for <= 28 days with WD therapy, only 5/28 treated > 90 days. Baseline average non-ceruloplasmin copper (NCC) was elevated (3.5mM), 25/28 had neurological manifestations at baseline and average UWDRS part III was 22. Modified Nazer score ranged from 1 to 5. Adverse events (AEs) included reversible elevated liver tests (n=5, of which 3 were related to per protocol dose escalation) and neutropenia (n=2). After the initiation dose was reduced from 60 mg daily to 15-30 mg QD and dose escalation limited to 60 mg QD, WTX101 was well tolerated with few AEs. Hepatic status (ALT, INR and bilirubin) and the modified Nazer score improved or remained stable in all patients. NCC (adjusted for molybdenum) decreased over time on treatment. Other Cu measurements (exchangeable Cu, total serum Cu, 24-hour urinary Cu excretion) indicate a similar de-coppering pattern. The UWDRS part III scores largely improved in patients with neurological manifestations, or was stable in those without. Daily activity status (UWDRS part II) showed similar improvement. Summary WTX101 appears safe and well tolerated as initial therapy in patients with WD. Improvements in hepatic and neurologic disease, Cu metabolism and daily activity status over time was observed with WTX101 treatment. Further data are being accrued. Conclusion Further clinical evaluation of WTX101 is warranted to establish its safety and efficacy for the initial treatment of WD. The potential for once daily dosing will increase patient convenience and treatment adherence.",adverse drug reaction;chelation;clinical evaluation;clinical trial;controlled clinical trial;controlled study;copper metabolism;daily life activity;diagnosis;excretion;human;human tissue;international normalized ratio;liver disease;major clinical study;multicenter study;neurologic disease;neutropenia;open study;rating scale;safety;side effect;Wilson disease;bilirubin;molybdenum;zinc,"Schilsky, M. L.;Askari, F. K.;Ferenci, P.;Ala, A.;Czlonkowska, A.;Nicholl, D. J.;Bronstein, J.;Bega, D.;Weiss, K. H.",2016,October,,0,0,
1137,Utility of serum zinc level to predict severity of Wilson disease,"BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder characterised by copper accumulation. Zinc (Zn), a copper antagonist used as treatment in WD, can inhibit copper absorption in intestine by up regulation of metallothionines (MTs). However, there has been no study of the link between Zn and WD severity. our aim were to evaluate serum Zn level in a variety of liver diseases and to study its correlation with the new Wilson index (WI) score (1) used to predict severity of WD. METHODS: Medical records of 26 patients with WD (8 WD with acute liver failure (ALF) and 18 WD-non-ALF) and 69 patients with non-WD (31 nonalcoholic fatty liver disease (NAFLD), 29 autoimmune hepatitis (AIH) and 9 indeterminate cause of ALF), who had initial serum Zn data before disease diagnosis, were reviewed in our tertiary hospital from 2005 to 2015. All WD children had disease causing mutations identified and the new WI score was calculated in all. Corrected Zn was calculated by Corrected Zn<inf>patient</inf> = (0.25xZn<sup>normal</sup>) + ((albuminnormal albuminpatient)x( Zn<inf>patient</inf> - (0.25xZn<sup>normal</sup>)). Correlation between corrected Zn level and score from new WI were statistically analyzed by Pearson Correlation. RESULTS: WD-ALF had lower corrected Zn level compared to WD-non- ALF, NAFLD, AIH and indeterminate cause of ALF (7.3 (5.2- 11.6), 13.8 (6.1-20.2), 13.7 (11.2-16.7), 9.9 (5.3-31.4) and 11.4 (7.6-17.8), respectively, P < 0.05). The demographic data and laboratory results are shown in table. Indeed, there was significant correlation between corrected Zn level and new WI score in WD patients (r = - 0.554, P value = 0.004). Conclusions: Serum Zn level can predict phenotypic severity of WD. Particularly, low serum Zn level can discriminate WD-ALF from indeterminate cause of ALF. (1) Dhawan A, Taylor RM, Cheeseman P, et al. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. (Table Presented).",acute liver failure;autoimmune hepatitis;child;controlled study;demography;diagnosis;genetic predisposition;human;human tissue;liver transplantation;major clinical study;medical record;mutation;nonalcoholic fatty liver;statistical significance;tertiary care center;Wilson disease;zinc blood level,"Sintusek, P.;Kyrana, E.;Dhawan, A.",2016,October,,0,0,
1138,Commentary: The case for abandoning therapeutic chelation of copper ions in Alzheimer's disease,,Alzheimer's disease;Beta-amyloid peptide;Chelation therapy;Copper;Metals;Alzheimer disease/dt [Drug Therapy];Alzheimer Disease Assessment Scale;ATP7B gene;brain level;cognitive defect/dt [Drug Therapy];copper blood level;copper brain level;drug efficacy;drug response;gene;gene frequency;gene mutation;genetic variability;human;note;oxidative stress;protein blood level;treatment outcome;Wilson disease;amyloid beta protein/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper ion/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Squitti, R.;Salustri, C.;Rongioletti, M.;Siotto, M.",2017,25 Sep,http://dx.doi.org/10.3389/fneur.2017.00503,0,0,
1139,Liver Transplantation in Wilson's Disease with Neurological Impairment: Evaluation in 4 Patients,"Background: The aim of this work is to report our early experiences about the benefits of liver transplantation (LT) in the treatment of persistent neurological symptoms in Wilson's disease (WD) patients. Methods: We describe our findings in 4 WD patients with neurological impairment or symptoms treated by LT: 2 patients had transplants due to worsening of neurological symptoms despite long-term appropriate medical treatment. The other 2 required LT because of symptoms associated with liver failure. Patients were evaluated using the modified Rankin scale and the Unified Wilson's Disease Rating Scale (UWDRS). Results: The 4 patients experienced neurological improvement after LT. The pre-LT Rankin score of the 2 patients transplanted due to neurological impairment was 4 compared to 3 and 2, respectively, post LT. The pre-LT Rankin scores of the 2 WD cases transplanted because of hepatic failure were 1 and 2, respectively, compared to 0 in both cases post LT. UWDRS score improved in 2 cases and remained stable in 1 less severely impaired case. Brain MRI abnormalities proved partially reversible in 3 patients and remained stable for 1 patient. Conclusions: These results suggest that LT could be envisaged for neurologically impaired WD patients. © 2016 S. Karger AG, Basel. Copyright: All rights reserved.",Copper chelator;Dystonia;Liver transplantation;Neurological disability;Wilson's disease;adolescent;article;bradykinesia;Burkitt lymphoma/dt [Drug Therapy];case report;dysarthria;dysphagia;extrapyramidal syndrome;female;follow up;gastrostomy;genetic screening;human;hypersalivation;limb tremor;liver failure;liver function test;male;Model For End Stage Liver Disease Score;neurologic disease/dt [Drug Therapy];nuclear magnetic resonance imaging;priority journal;Rankin scale;thrombocytopenia;Wilson disease/di [Diagnosis];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];cyclophosphamide/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];rituximab/dt [Drug Therapy];tacrolimus;trientine;vincristine/dt [Drug Therapy];zinc,"Laurencin, C.;Brunet, A. S.;Dumortier, J.;Lion-Francois, L.;Thobois, S.;Mabrut, J. Y.;Dubois, R.;Woimant, F.;Poujois, A.;Guillaud, O.;Lachaux, A.;Broussolle, E.",2017,01 Jan,http://dx.doi.org/10.1159/000452658,0,0,
1140,Maintenance Zinc therapy after initial Penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting,"Background: Experience with Zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. Aim: To study the efficacy of Penicillamine followed by Zinc in treating symptomatic hepatic Wilson's disease. Methods: We retrospectively analysed case records of 31 symptomatic hepatic WD patients in whom disease severity scores (Child's, MELD, Nazer's and nNew Wilson iIndex score) and 24-hour Urinary copper were compared at 3 three time points-baseline at presentation, at transition from Penicillamine to Zinc, and at end of follow-up. Results: Of the 31 patients with symptomatic hepatic WD studied, 10 had associated neuropsychiatric manifestations of WD. Penicillamine was changed to Zinc sulfate either due to financial constraints (in 28 patients) or due to adverse effects of Penicillamine (in 3three). Child's grade was A in 6 six patients, B in 5 five, and C in 17 at presentation (baseline). Duration of initial Penicillamine chelation therapy was 134 (2-320) weeks, median (range) and of subsequent Zinc therapy was 363 (35-728) weeks. There was significant improvement in liver function tests and disease severity scores (Nazer's, nNew Wilson index, Child's and MELD score) at transition from Penicillamine to Zinc compared to with baseline. This improvement was maintained till end of study period. 17 Seventeen patients with Child C cirrhosis at presentation were treated with Penicillamine for 111 (2-320) weeks followed by Zinc for 344 (41-652) weeks, of whom 15 had significant improvement in liver function and disease severity scores until end of follow-up. 3 Three of 31 study patients died at 284, 112, and 437 weeks. No patient underwent liver transplantation. Conclusions: Penicillamine followed by Zinc maybe safe and effective treatment in resource constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Our data also suggests that some patients with decompensated cirrhosis due to Wilson's disease may be managed with medical treatment, avoiding liver transplantation.",adverse drug reaction;chelation therapy;child;clinical article;clinical trial;controlled clinical trial;controlled study;decompensated liver cirrhosis;drug therapy;female;follow up;human;information processing;liver function test;liver transplantation;male;mental disease;Model For End Stage Liver Disease Score;retrospective study;side effect;Wilson disease;penicillamine;zinc;zinc sulfate,"Gupta, P.;Choksi, M.;Goel, A.;Zachariah, U.;Sajith, K. G.;Ramachandran, J.;Chandy, G.;Kurian, G.;Eapen, C. E.",2017,September,http://dx.doi.org/10.1111/jgh.13878,0,1,
1141,Psychiatric comorbidity in Wilson's disease,"Wilson's disease (WD) is a relatively rare autosomal recessive inherited disorder causing copper accumulation in different organs, mainly the liver and brain. Psychiatric disturbances represent a diagnostic and therapeutic issue in WD. A search for relevant articles was carried out on PubMed/Medline, Scopus, and Google Scholar, for papers focused on psychiatric disorders in WD published between 1985-2016. Ninety-two articles were included in this review, showing the findings from 35 observational and case-control studies and 57 case reports. This study discussed the findings on the prevalence of psychiatric symptoms in WD, their impact on the life of those diagnosed, and the efficacy of available treatments on the psychiatric outcomes of WD. Psychiatric disorders are confirmed frequent in WD, with a high prevalence of mood disorders, and contribute to worse Quality-of-Life and psychosocial outcomes. Because specific therapies for WD lead to a good life expectancy, adherence to medicaments and clinical monitoring should be warranted by a multidisciplinary approach, including a hepathologic, neurologic, and psychiatric careful evaluation and education of those affected and their relatives. Copyright © 2017 Institute of Psychiatry and Johns Hopkins University.",burden of disease;mood disorders;psychiatric comorbidity;quality-of-life;Wilson's disease;catatonia/th [Therapy];clinical feature;disease burden;electroconvulsive therapy;general condition deterioration;human;life expectancy;medication compliance;mental disease/di [Diagnosis];mental disease/dm [Disease Management];mental disease/ep [Epidemiology];mental disease/et [Etiology];outcome assessment;overall survival;pathogenesis;patient compliance;patient monitoring;prevalence;priority journal;quality of life;review;systematic review;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];alpha tocopherol;chelating agent;lithium;penicillamine;tetrathiomolybdic acid;trientine;zinc derivative,"Mura, G.;Zimbrean, P. C.;Demelia, L.;Carta, M. G.",2017,03 Sep,http://dx.doi.org/10.1080/09540261.2017.1311845,0,0,
1142,Wilson's disease: The 60<sup>th</sup> anniversary of walshe's article on treatment with penicillamine,"This historical review describes Professor Walshe's seminal contribution to the treatment of Wilson's disease on the 60th anniversary of his pioneering article on penicillamine, the first effective treatment for the condition. Copyright © 2017, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.",Hepatolenticular degeneration;Penicillamine;Therapeutics;dystonia;gene mutation;genetic analysis;human;motor dysfunction;neurotoxicity;note;parkinsonism;prevalence;skin defect;Wilson disease/di [Diagnosis];thiomolybdic acid,"Teive, H. A. G.;Barbosa, E. R.;Lees, A. J.",2017,,http://dx.doi.org/10.1590/0004-282x20160166,0,0,
1143,Yeast as a model for the identification of novel survival-promoting compounds applicable to treat degenerative diseases,"Programmed cell death (PCD) plays an important role in development and normal metabolic functioning of organisms. Excessive cell death is the cause of many degenerative diseases, like neurodegenerative disorders and Wilson's disease, for which current therapies remain insufficient. Current therapies are mainly focused on decreasing the disease symptoms following cell death, rather than blocking the cell death process itself. The latter can be obtained by either decreasing the presence of the toxic trigger (like protein aggregation in case of many commonly known neurodegenerative diseases) or by blocking death-inducing signaling cascade(s). Given the high conservation in PCD processes between yeast and mammalian cells, in this review, we will focus on yeast as a model organism to study PCD-related diseases as well as on its use for drug discovery purposes. More specifically, we will provide a comprehensive overview of new compounds, which were identified in yeast-based drug screens, that either decrease the amount of toxic trigger or inhibit PCD signaling cascades under PCD-inducing conditions. Copyright © 2016 Elsevier Ireland Ltd","Neurodegenerative diseases;Programmed cell death;Survival-promoting activity;Wilson's disease;Yeast-based models;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/dt [Drug Therapy];apoptosis;cell survival;clinical trial (topic);disease course;enzyme inhibition;homeostasis;human;Huntington chorea/dt [Drug Therapy];Huntington chorea/et [Etiology];molecular library;necroptosis;nonhuman;Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];phenotype;pilot study;protein aggregation;protein processing;review;Saccharomyces cerevisiae;signal transduction;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];1,2,3,4 tetrahydroquinoline derivative/ct [Clinical Trial];1,2,3,4 tetrahydroquinoline derivative/dt [Drug Therapy];2 methoxy vinyl sulfone/ct [Clinical Trial];2 methoxy vinyl sulfone/dt [Drug Therapy];4,5 dianilinophthalimide/ct [Clinical Trial];4,5 dianilinophthalimide/dt [Drug Therapy];ak 1/ct [Clinical Trial];ak 1/dt [Drug Therapy];ak 7/ct [Clinical Trial];ak 7/dt [Drug Therapy];amyloid beta protein/ct [Clinical Trial];amyloid beta protein/dt [Drug Therapy];cyclopeptide/ct [Clinical Trial];cyclopeptide/dt [Drug Therapy];cyclopeptide MCoCP4/ct [Clinical Trial];cyclopeptide MCoCP4/dt [Drug Therapy];cyclopeptide MCoTI I/ct [Clinical Trial];cyclopeptide MCoTI I/dt [Drug Therapy];donepezil/ct [Clinical Trial];donepezil/dt [Drug Therapy];galantamine/ct [Clinical Trial];galantamine/dt [Drug Therapy];gluconate zinc/ct [Clinical Trial];gluconate zinc/dt [Drug Therapy];humanin/ct [Clinical Trial];humanin/dt [Drug Therapy];levodopa/ct [Clinical Trial];levodopa/dt [Drug Therapy];memantine/ct [Clinical Trial];memantine/dt [Drug Therapy];minocycline/ct [Clinical Trial];minocycline/dt [Drug Therapy];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];pramipexole/ct [Clinical Trial];pramipexole/dt [Drug Therapy];presenilin 1/ct [Clinical Trial];presenilin 1/dt [Drug Therapy];protein inhibitor/ct [Clinical Trial];protein inhibitor/dt [Drug Therapy];rasagiline/ct [Clinical Trial];rasagiline/dt [Drug Therapy];rivastigmine/ct [Clinical Trial];rivastigmine/dt [Drug Therapy];rotigotine/ct [Clinical Trial];rotigotine/dt [Drug Therapy];selegiline/ct [Clinical Trial];selegiline/dt [Drug Therapy];sulfone derivative/ct [Clinical Trial];sulfone derivative/dt [Drug Therapy];sulfosalicylic acid/ct [Clinical Trial];sulfosalicylic acid/dt [Drug Therapy];trientine/ct [Clinical Trial];trientine/dt [Drug Therapy];unclassified drug;unindexed drug;zinc acetate/ct [Clinical Trial];zinc acetate/dt [Drug Therapy];zinc sulfate/ct [Clinical Trial];zinc sulfate/dt [Drug Therapy]","Verbandt, S.;Cammue, B. P. A.;Thevissen, K.",2017,01 Jan,http://dx.doi.org/10.1016/j.mad.2016.06.003,0,0,
1144,Pathological fracture of femoral neck leading to a diagnosis of Wilson's disease: A case report and review of literature,"Wilson's disease (WD) is a rare inherited disorder of copper metabolism. It chiefly has hepatic, neurological and ophthalmic manifestations. Although osteoporosis, rickets and early arthritis are common features of WD, they are under-recognized. Musculoskeletal manifestations very rarely lead to diagnosis of the disease. Here we present a case of a 12-year-old girl who presented with a 3-month-old pathological fracture of neck of femur. WD was diagnosed on investigating the cause of the pathological fracture, which was managed by performing a conventional McMurray's intertrochanteric osteotomy. At 6 months follow up, fracture had united and patient was able to ambulate with support. WD can be a rare cause of pathological fracture. A high index of suspicion must be maintained in patients of pathological fracture presenting with associated neuropsychiatric or hepatic manifestations. Copyright © 2017 The Korean Society for Bone and Mineral Research.",Femur neck;Fractures spontaneous;Hepatolenticular degeneration;article;case report;ceruloplasmin blood level;child;consultation;copper blood level;copper urine level;disease association;female;femoral neck fracture/co [Complication];femoral neck fracture/di [Diagnosis];femoral neck fracture/su [Surgery];femur osteotomy;fluoroscopy;general anesthesia;hip radiography;human;physical examination;postoperative period;school child;short stature;slit lamp microscopy;urine level;weight bearing;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper ion/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];pyridoxine/dt [Drug Therapy];pyridoxine/po [Oral Drug Administration],"Bhatnagar, N.;Lingaiah, P.;Lodhi, J. S.;Karkhur, Y.",2017,,http://dx.doi.org/10.11005/jbm.2017.24.2.135,0,0,
1145,A case of Wilson's disease presenting with paroxysmal dystonia,,adult;case report;ceruloplasmin blood level;clinical article;cornea disease;differential diagnosis;human;involuntary movement;letter;male;nuclear magnetic resonance imaging;paroxysmal dystonia/dr [Drug Resistance];smoking;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];carbamazepine;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];trientine/dt [Drug Therapy],"Kim, H. J.;Yoon, J. H.",2017,01 Oct,http://dx.doi.org/10.1007/s10072-017-3008-4,0,0,
1146,The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders,"Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development. Objectives: The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD. Methods: This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD. Results: Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants. Discussion: These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD. Copyright © 2015 Informa UK Limited, trading as Taylor & Francis Group.","asd;Developmental neurotoxicity;Inflammation;Maternal nutrition;Micronutrients;Risk factor;autism;brain development;female;homeostasis;human;maternal exposure;maternal obesity;metabolism;neurotoxicity;nutritional deficiency;nutritional status;priority journal;review;teratogenicity;Wilson disease;4,4' isopropylidenediphenol;alcohol;copper;cytokine;dihydrofolate reductase;endotoxin;heavy metal;iron;phthalic acid bis(2 ethylhexyl) ester;trace element;valproic acid;vitamin B group;zinc","Nuttall, J. R.",2017,21 Apr,http://dx.doi.org/10.1080/1028415X.2015.1103437,0,0,
1147,A 6-year-old boy with Wilson disease-A diagnostic dilemma,"A 6-year-old boy presented with 2 months history of progressive abdominal distension and jaundice. He was deeply icteric with ascites, hepatosplenomegaly, hyperbilirubinemia, raised transaminases, and coagulopathy. Viral markers and slit lamp examination for Kayser-Fleischer ring were negative. Serum ceruloplasmin and 24-h urinary copper post-D-pencillamine challenge were normal. Anti-smooth muscle antibody was positive 1:20, and liver biopsy showed micronodular cirrhosis with abundant Mallory hyaline and stainable copper deposits. The liver histology was indicative of Indian childhood cirrhosis, whereas the presence of autoantibodies, elevated transaminases, and increased globulin was suggestive of autoimmune hepatitis. Gene studies identified p.R969Q mutation in ATP7B gene, which solved the dilemma and confirmed the diagnosis of Wilson disease (WD). We report a clinicopathological conference of this boy to highlight the challenges faced by pediatricians in the diagnosis of Wilson disease. . Copyright © 2017, Indian Society of Gastroenterology.",Autoimmune hepatitis;Indian childhood cirrhosis;p.R969Q mutation;Wilson disease;abdominal distension;ascites;atomic absorption spectrometry;case report;ceruloplasmin blood level;child;conference paper;echocardiography;ferritin blood level;foot edema;gastrointestinal endoscopy;hemolysis;hepatosplenomegaly;human;human tissue;hyperbilirubinemia;immunofluorescence;jaundice;lethargy;liver biopsy;liver histology;low drug dose;male;palmar erythema;petechia;preschool child;sepsis;slit lamp microscopy;thorax radiography;vomiting;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];C reactive protein/ec [Endogenous Compound];cefotaxime/iv [Intravenous Drug Administration];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];fresh frozen plasma;globulin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];hyalin/ec [Endogenous Compound];immunoglobulin G/ec [Endogenous Compound];lactulose/po [Oral Drug Administration];penicillamine;phytomenadione;prednisolone/po [Oral Drug Administration];proton pump inhibitor;serum albumin/ec [Endogenous Compound];smooth muscle antibody;spironolactone/po [Oral Drug Administration];ursodeoxycholic acid/po [Oral Drug Administration],"Ganesh, R.;Suresh, N.;Vasanthi, T.;Sathiyasekaran, M.;Thulasiraman, R.",2017,01 Mar,http://dx.doi.org/10.1007/s12664-017-0746-4,0,0,
1148,Copper(I)-binding properties of de-coppering drugs for treatment of Wilson disease,"Wilson disease (WD) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the P-type copper ATPase, ATP7B, which transports copper out of cells and is therefore crucial for biliary excretion of excess copper. WD is characterized by toxic accumulation of copper primarily in the liver and brain, leading to liver disorders and/or neuropsychiatric symptoms. Unlike many other genetic disorders, WD is treatable, primarily by copper chelation therapy, which mobilizes copper from the organism, enhancing its urinary excretion. Although a number of de-coppering drugs are currently available, their Cu (I)-binding affinities and interaction with essential cellular copper proteins have not been quantitatively characterized to date. By using an ESI MS-based approach we have determined the Cu(I)- binding affinities of five major de-coppering drugs - penicillamine, trientine, 2,3-dimercapto-1-propanol, 2,3-dimercaptosuccinate and tetrathiomolybdate - by exploring their ability to extract Cu(I) ions from two cellular Cu(I)-binding proteins, which have different Cu(I)-binding affinities. We report that Cu (I)-binding affinity of de-coppering drugs vary by four orders of magnitude and depends from the number of sulfur atoms in the drug molecule. Obtained structure-activity relationships are important for understanding the action of copper-chelating drugs and elaboration of new generation drugs that may provide better therapeutic outcomes.",binding affinity;chelation;electrospray mass spectrometry;human;Wilson disease;copper protein;cuprous ion;dimercaprol;penicillamine;succimer;tetrathiomolybdic acid;trientine,"Smirnova, J.;Golendukhina, E.;Jarving, I.;Tougu, V.;Plitz, T.;Palumaa, P.",2017,September,http://dx.doi.org/10.1111/febs.14174,0,0,
1149,Characterization of ZEB2 enhancers during brain development,"Zinc finger E-box binding homeobox (ZEB2) is a transcription repressor that is essential regulator of the nervous system during development. De-novo heterozygous mutations in the ZEB2 are associated with multiple neurological defects, including Mowat- Wilson syndrome, due to haploinsufficiency of ZEB2 expression during development. Therefore, mutations in ZEB2 enhancers that regulate its neuronal expression might lead to a similar phenotype. However, ZEB2 enhancers are yet to be characterized. Using enhancer associated ChIP-seq data, we identified 13 sequences in the Zeb2 locus that might function as neuronal enhancers during development. Using zebrafish enhancer assay, we characterized nine neuronal enhancers, when four function as notochord enhancers and two function as specific neuron enhancers. Interestingly, the four notochord enhancers which drove similar GFP expression pattern do not have homology in their sequence, which led us to further determine the transcription factors that activate these enhancers. We found the TF repertoire that is likely to regulate the activity of these enhancers that required for the spatiotemporal expression of ZEB2 during neuronal development. The characterized enhancers shed light on the mechanism of action of ZEB2 regulation and can serve as potential sequences that should be screened for mutations in patients whom no mutation at ZEB2 coding region were found.",adult;brain development;chromatin immunoprecipitation;enhancer region;gene mutation;human;nerve cell;nonhuman;notochord;zebra fish;endogenous compound;transcription factor,"Bar Yaackov, R.;Birnbaum, R.",2017,September,http://dx.doi.org/10.1111/febs.14174,0,0,
1150,Iron and copper in fetal development,"Copper and iron are both essential micronutrients. Because they can both accept and donate electrons, they are central to many energy dependent chemical reactions. For example, copper is a critical part of ferroxidase enzymes ceruloplasmin, hephaestin and zyklopen, as well as enzymes such as dopamine-beta-monoxygenase, while iron is part of the catalytic site of many cytochromes and enzymes involved in fatty acid desaturation. Unsurprisingly, therefore, copper and iron deficiency, especially during pregnancy, when cell proliferation and differentiation are very active, sub-optimal nutrient status can lead to serious consequences. These problems can persist into adulthood, with an increased risk of mental problems such as schizophrenia and, in animal models at least, hypertension and obesity. In this review, we consider what these problems are and how they may arise. We examine the role of copper and iron deficiencies separately during fetal development, in terms of birth outcome and then how problems with status in utero can have long term sequelae for the offspring. We examine several possible mechanisms of action, both direct and indirect. Direct causes include, for example, reduced enzyme activity, while indirect ones may result from changes in cytokine activity, reductions in cell number or increased apoptosis, to name but a few. We examine a very important area of nutrition-interactions between the micronutrients and conclude that, while we have made significant advances in understanding the relationship between micronutrient status and pregnancy outcome, there is still much to be learned. © 2011 Elsevier Ltd.",Copper;Deficiency;Iron;Pregnancy;aerobic metabolism;anemia/dt [Drug Therapy];apoptosis;cell count;congenital malformation/si [Side Effect];copper deficiency/et [Etiology];copper metabolism;cytotoxicity;decidualization;dietary intake;embryo development;enzyme activity;enzyme deficiency/et [Etiology];fetal well being;fetus development;fetus growth;fetus weight;genetic disorder;human;iron deficiency/et [Etiology];iron deficiency anemia/et [Etiology];iron metabolism;lung disease;maternal disease;maternal nutrition;nonhuman;nutrition;organogenesis;perinatal development;placenta function;pregnancy outcome;progeny;respiratory distress syndrome;review;teratogenicity;trophoblast;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];cytokine/ec [Endogenous Compound];dopamine/ec [Endogenous Compound];iron/dt [Drug Therapy];iron/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];thiobarbituric acid reactive substance/ec [Endogenous Compound];trace element/ec [Endogenous Compound];tumor necrosis factor alpha/ec [Endogenous Compound],"Gambling, L.;Kennedy, C.;McArdle, H. J.",2011,August,http://dx.doi.org/10.1016/j.semcdb.2011.08.011,0,0,
1151,Rare ER protein misfolding-mistrafficking disorders: Therapeutic developments,"The presence of a functional protein at the appropriate location in the cell is the result of the processes of transcription, translation, folding and trafficking to the correct destination. There are numerous diseases that are caused by protein misfolding, mainly due to mutations in the respective gene. The consequences of this misfolding may be that proteins effectively lose their function, either by being removed by the cellular quality control machinery or by accumulating at the incorrect intracellular or extracellular location. A number of mutations that lead to protein misfolding and affect trafficking to the final destination, e.g. Cystic fibrosis, Wilson's disease, and Progressive Familial Intrahepatic 1 cholestasis, result in proteins that retain partial function if their folding and trafficking is restored either by molecular or pharmacological means. In this review, we discuss several mutant proteins within this class of misfolding diseases and provide an update on the status of molecular and therapeutic developments and potential therapeutic strategies being developed to counter these diseases. Copyright © 2017 Elsevier Ltd",erad;Misfolding;Mutations;Trafficking;cystic fibrosis/dt [Drug Therapy];Dubin Johnson syndrome/et [Etiology];Fabry disease/dt [Drug Therapy];Fabry disease/et [Etiology];familial hypercholesterolemia/et [Etiology];gene mutation;genetic transcription;human;intellectual impairment/et [Etiology];intrahepatic cholestasis/dt [Drug Therapy];intrahepatic cholestasis/et [Etiology];malignant neoplasm/dt [Drug Therapy];nephrogenic diabetes insipidus/et [Etiology];nonhuman;persistent hyperinsulinemic hypoglycemia of infancy/et [Etiology];protein folding;protein function;protein localization;protein misfolding;protein transport;pseudoxanthoma elasticum/et [Etiology];review;RNA translation;sitosterolemia/et [Etiology];Stargardt disease/et [Etiology];Tangier disease/et [Etiology];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];15 deoxyspergualin/pd [Pharmacology];4 phenylbutyric acid/dt [Drug Therapy];agalsidase beta/dt [Drug Therapy];cavosonstat/dt [Drug Therapy];celastrol/pd [Pharmacology];colestyramine/dt [Drug Therapy];cystic fibrosis transmembrane conductance regulator/cm [Drug Comparison];cystic fibrosis transmembrane conductance regulator/pr [Pharmaceutics];cystic fibrosis transmembrane conductance regulator/pd [Pharmacology];geldanamycin/pd [Pharmacology];heat shock protein 90 inhibitor/ct [Clinical Trial];heat shock protein 90 inhibitor/dt [Drug Therapy];herbimycin A/pd [Pharmacology];histone deacetylase inhibitor/pd [Pharmacology];ivacaftor plus lumacaftor/dt [Drug Therapy];liposome/pr [Pharmaceutics];miglustat/pd [Pharmacology];mitogen activated protein kinase inhibitor/pd [Pharmacology];mutant protein;penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];placebo;plasmid DNA/pr [Pharmaceutics];proteasome inhibitor/pd [Pharmacology];qr 010/dt [Drug Therapy];rifampicin/dt [Drug Therapy];riociguat/dt [Drug Therapy];tanespimycin/pd [Pharmacology];thapsigargin/pd [Pharmacology];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Hegde, R. N.;Subramanian, A.;Pothukuchi, P.;Parashuraman, S.;Luini, A.",2017,01 Apr,http://dx.doi.org/10.1016/j.tice.2017.02.001,0,0,
1152,Wilson's Disease Should Be Treated with Zinc rather than Trientine or Penicillamine,,blood brain barrier;chelation therapy;copper blood level;human;letter;mental health;monotherapy;neuroimaging;nuclear magnetic resonance imaging;practice guideline;priority journal;urinary excretion;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];gluconate zinc/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Avan, A.;De Bie, R. M. A.;Hoogenraad, T. U.",2017,01 Oct,http://dx.doi.org/10.1055/s-0037-1603975,0,0,
1153,The role of MRI in diagnosis and therapy monitorization of wilson's disease,"Purpose: Wilson's disease (WD) is a rare disorder of Copper metabolism, that arises from a mutation in ATP7B gene. The diagnosis of WD is usually established using blood tests and clinical findings. In this case report, we aimed emphasizing the contribution of magnetic resonance imaging (MRI) in the diagnosis of WD as well as monitorization of treatment A 19 years old female presented with a one year history of progressive dysarthria and nocturnal tremor in the right hand. In neurological exam-ination revealed dysarthria, postural and actional tremor and motor weak-ness in lower extremities. The EEG was unremarkable. Kayser-Fleischer rings were observed bilaterally. Blood test results were as follows: Serum ceruloplasmin 16,3 mg/dL (normal: 25-63 mg/dL), serum copper level 32 mug/dL normal: 70-140 mug/dL) and 24 h urine copper excretion 56,5 mug/day (normal 24 h urine excretion 20-50 mug/day)Abdominal ultrasonography revealed, heterogoneus liver echogenicity with a suggestion of surface nodularity. On cranial MRI, abnormal high T2 signal was observed in putamina, dorsal mesencephalon and pons. The patient was diagnosed with Wilson's Disease. Trientin and zinc treatment was initiated. After a month of therapy, patient was re-evaluated. There was significant decrease in tremor with motor functional gain. Repeat MRI showed significant decrease in the signal abnormalities detected previously. Result: MRI findings closely reflected the clinical response to therapy. Conclusion: Although not a primary diagnostic tool In WD, MRI may be helpful in both establishing the diagnosis and in documenting response to treatment.",adult;case report;ceruloplasmin blood level;congenital malformation;copper blood level;copper metabolism;diagnosis;dorsal region;dysarthria;echography;electroencephalogram;female;gene mutation;hand;human;human tissue;liver;lower limb;mesencephalon;nuclear magnetic resonance imaging;pons;treatment response;tremor;urinary excretion;Wilson disease;young adult;endogenous compound;Wilson disease protein;zinc,"Ozturk, O.;Ozturk, S.",2017,,http://dx.doi.org/10.1007/s00234-017-1872-5,0,0,
1154,Thrombotic microangiopathy in the frame of systemic diseases: Four cases from pediatric clinical practice,"Introduction: Thrombotic microangiopathies result from the interaction between predisposing factors and triggering events. Material and methods: We present four pediatric cases with unusual forms of thrombotic microangiopathy in the frame of systemic diseases. Results: Case 1: 5 years old, acute pancreatitis with complement activation and HUS-triad (hemolytic anemia, thrombocytopenia and acute renal failure). Early treatment with Eculizumab results in rapid hematological and renal remission. MRI shows anatomic variant (pancreas divisum) associated to high risk of spontaneous pancreatitis. Recurrence of pancreatitis under treatment with Eculizumab, with no signs of TMA. Genetic analysis shows risk haplotypes in CHF, MCP and CFHR3-CFHR1 deletion. Pancreatitis triggered aHUS or vice versa? Case 2: 2 years old, acute myeloid leukemia M5, after haploidentical BMT, complete chimerism. After BMT develops transfusion-dependent anemia, malignant hypertension and proteinuria. Transitory stabilization after suspension of cyclosporine. Progressive disease with two-fold increase of creatinine, renal biopsy shows TMA. Under treatment with Eculizumab normalization of blood pressure and renal function, no proteinuria. Hemoglobin recovery, no need for transfusions. Material for genetic testing from saliva (blood cells from donor), result pending. Case 3: 15 years old, previously healthy, presents with cholestasis and HUS-triad. Ocular evaluation shows Keyser-Fleischer Ring. Copper in urine and low ceruloplasmin confirm diagnosis of Wilson's disease. Hemolytic anemia only better under treatment with Trientine. Progressive recovery of hemoglobin and renal function. Marked complement activation, CFB-Antibodies and CFHR5 variant. Case 4: 10 years old, Wilson's disease. Three years after liver transplantation presents HUS-triad in the frame of viral infection. Recovery after suspension of treatment with Tacrolimus and Everolimus. Carrier of CHR1 and 3 homozygous deletions. Conclusions: This cases picture the relevance of considering TMA in non-aHUS related diseases in which complement activation and endothelial damagemay be trigger or consequence of complement activation. The relevance of complement gene polymorphisms as TMA predisposing condition is not yet well understood.",acute kidney failure;acute myeloid leukemia;acute pancreatitis;blood cell;blood pressure;cancer recurrence;child;chimera;cholestasis;clinical practice;complement activation;diagnosis;DNA polymorphism;drug combination;gene deletion;genetic analysis;genetic screening;haplotype;hemolytic uremic syndrome;homozygosity;human;human cell;human tissue;kidney biopsy;kidney function;liver transplantation;malignant hypertension;nuclear magnetic resonance imaging;pancreas divisum;proteinuria;relapse;remission;saliva;suspension;systemic disease;thrombotic thrombocytopenic purpura;urine;virus infection;Wilson disease;ceruloplasmin;creatinine;cyclosporin;eculizumab;endogenous compound;everolimus;hemoglobin;tacrolimus;trientine,"Rosales, A.;Madrid, A.;Munoz, M.;Quintero, J.;Alonso, L.;Chocron, S.;De Cordoba, S. R.;Ariceta, G.",2017,September,http://dx.doi.org/10.1007/s00467-017-3753-x,0,0,
1155,Canine Copper-Associated Hepatitis,"Copper-associated hepatitis is recognized with increasing frequency in dogs. The disease is characterized by centrolobular hepatic copper accumulation, leading to hepatitis and eventually cirrhosis. The only way to establish the diagnosis is by histologic assessment of copper distribution and copper quantification in a liver biopsy. Treatment with the copper chelator D-penicillamine is the most commonly used treatment. In addition, a low-copper/high-zinc diet can help prevent accumulation or reaccumulation of hepatic copper. Mutations in the copper metabolism genes COMMD1 or ATP7A and ATP7B have been associated with hepatic copper concentrations in Bedlington terriers and Labrador retrievers respectively. In the Labrador retriever, dietary copper intake contributes strongly to the disease phenotype. Copyright © 2016 Elsevier Inc.","atp7a;atp7b;Bedlington terrier;commd1;Dog;Labrador retriever;Liver;Wilson disease;chelation therapy;copper associated hepatitis/di [Diagnosis];copper associated hepatitis/dt [Drug Therapy];copper associated hepatitis/th [Therapy];copper blood level;copper deficiency;copper metabolism;diet therapy;dog breed;drug intermittent therapy;drug withdrawal;Fanconi renotubular syndrome;fine needle aspiration biopsy;gene mutation;genetic predisposition;hepatitis/di [Diagnosis];hepatitis/dt [Drug Therapy];hepatitis/th [Therapy];human;liver biopsy;liver cirrhosis;liver histology;Menkes syndrome;nonhuman;recommended drug dose;review;scoring system;terrier;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];gluconate zinc/dt [Drug Therapy];gluconate zinc/to [Drug Toxicity];gluconate zinc/po [Oral Drug Administration];Menkes protein/ec [Endogenous Compound];microRNA 122/ec [Endogenous Compound];n,n' bis(2 aminoethyl) 1,3 propanediamine/dt [Drug Therapy];n,n' bis(2 aminoethyl) 1,3 propanediamine/po [Oral Drug Administration];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/po [Oral Drug Administration];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/to [Drug Toxicity];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];Wilson disease protein/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy];zinc acetate/to [Drug Toxicity];zinc acetate/po [Oral Drug Administration];zinc sulfate/dt [Drug Therapy];zinc sulfate/to [Drug Toxicity];zinc sulfate/po [Oral Drug Administration]","Dirksen, K.;Fieten, H.",2017,01 May,http://dx.doi.org/10.1016/j.cvsm.2016.11.011,0,0,
1156,Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination,"The mechanisms that coordinate and balance a complex network of opposing regulators to control Schwann cell (SC) differentiation remain elusive. Here we demonstrate that zinc-finger E-box-binding homeobox 2 (Zeb2, also called Sip1) transcription factor is a critical intrinsic timer that controls the onset of SC differentiation by recruiting histone deacetylases HDAC 1 and 2 (HDAC1/2) and nucleosome remodeling and deacetylase complex (NuRD) co-repressor complexes in mice. Zeb2 deletion arrests SCs at an undifferentiated state during peripheral nerve development and inhibits remyelination after injury. Zeb2 antagonizes inhibitory effectors including Notch and Sox2. Importantly, genome-wide transcriptome analysis reveals a Zeb2 target gene encoding the Notch effector Hey2 as a potent inhibitor for Schwann cell differentiation. Strikingly, a genetic Zeb2 variant associated with Mowat-Wilson syndrome disrupts the interaction with HDAC1/2-NuRD and abolishes Zeb2 activity for SC differentiation. Therefore, Zeb2 controls SC maturation by recruiting HDAC1/2-NuRD complexes and inhibiting a Notch-Hey2 signaling axis, pointing to the critical role of HDAC1/2-NuRD activity in peripheral neuropathies caused by ZEB2 mutations. Copyright © 2016 Nature America, Inc.",animal cell;animal experiment;animal tissue;article;controlled study;gene;gene deletion;genetic variability;genome analysis;mouse;nerve cell differentiation;nonhuman;peripheral nerve;peripheral neuropathy;priority journal;protein protein interaction;remyelinization;Schwann cell;signal transduction;zeb2 gene;corepressor protein/ec [Endogenous Compound];Hey2 protein/ec [Endogenous Compound];histone deacetylase/ec [Endogenous Compound];homeodomain protein;Notch receptor/ec [Endogenous Compound];nucleosome remodeling and deacetylase complex/ec [Endogenous Compound];transcription factor Sox2/ec [Endogenous Compound];transcriptome/ec [Endogenous Compound];unclassified drug;zinc finger E box binding homeobox 2 protein,"Wu, L. M. N.;Wang, J.;Conidi, A.;Zhao, C.;Wang, H.;Ford, Z.;Zhang, L.;Zweier, C.;Ayee, B. G.;Maurel, P.;Zwijsen, A.;Chan, J. R.;Jankowski, M. P.;Huylebroeck, D.;Lu, Q. R.",2016,01 Aug,http://dx.doi.org/10.1038/nn.4322,0,0,
1157,Clinical features of Wilson's disease in Peru: Review of eight cases,"Objective: To describe the clinical features of Wilson's disease patients followed at Instituto Nacional de Ciencias Neurologicas (INCN), Lima, Peru, between 1995 and 2013. Background: Wilson's disease (WD) is an autosomal recessive disorder associated to copper metabolism dysfunction due to mutation of ATP7B gene. WD presents with hepatic, neurological, psychiatric, and ophthalmic and others manifestations. Neurological symptoms include parkinsonism, dystonia and ataxia. The clinical course is highly variable and diagnosis delay is not uncommon. Diagnosis of WD is based on clinical, biochemical and genetic analysis when available genetic features. Early diagnosis is crucial to prevent or minimize permanent neurological complications. Methods: Retrospective analysis of all patients with clinical diagnosis of WD followed at INCN (Movement Disorders Unit and Neurogenetics Research Center). Demographic and clinical data as well as biochemical parameters (especially, serum ceruloplasmin and 24 hours urinary copper excretion); neuroimaging and specialized consultations were retrieved from clinical records. IRB Approval from local institution was obtained for this study. Results: Eight out of 19 patients identified were included in the study. 87.5 % (7) were males. Our WD patients presented with a mean age of 26 [17-44] years and a mean age at onset of 23.7 [12-44] years; the mean time from symptom onset to diagnostic was 20.3 [3-72] months. Parkinsonism was the predominant phenotype in this group, and together with dysarthria were the two most frequent symptoms at onset (37.5%). Kayser-Fleischer ring was confirmed in 62.5% (5) of the patients. The average serum ceruloplasmin concentration was 12.5 mg/dl [2.3-23.4] and average 24 hours urinary cooper excretion was 109.6 ug/24 horas [33.2-278]. The commonest finding on MRI brain was putamen signal changes (50%) followed by thalamus (37.5%). 87.5% (7) patients started treatment soon after the diagnosis and 75% (7) received therapy with penicillamine. Conclusions: This is the first case series on WD in Peruvian population. WD cases in our Peruvian cohort appear similar to the ones described in other populations; however diagnosis delay is higher than other reported worldwide.",adolescent;adult;ataxia;case study;ceruloplasmin blood level;clinical article;clinical feature;clinical trial;consultation;delayed diagnosis;diagnosis;dysarthria;dystonia;early diagnosis;excretion;genetic analysis;human;human tissue;information processing;male;neuroimaging;neurologic disease;neurological complication;nuclear magnetic resonance imaging;onset age;parkinsonism;Peru;Peruvian;phenotype;putamen;retrospective study;thalamus;Wilson disease;endogenous compound;penicillamine,"Sarapura, E.;Ramirez-Quinones, J.;Cornejo-Olivas, M.;Torres, L.",2017,,http://dx.doi.org/10.1002/mds.26972,0,1,
1158,D-penicillamine-induced elastosis perforans serpiginosa,,adult;case report;drug induced disease;dyskeratosis;elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/si [Side Effect];histopathology;human;human tissue;letter;male;medical history;parakeratosis;physical examination;rash;skin biopsy;skin disease/di [Diagnosis];skin disease/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Yao, X. Y.;Wen, G. D.;Zhou, C.;Liu, B. Y.;Du, J.;Chen, Z.;Zhang, J. Z.",2017,20 Aug,http://dx.doi.org/10.4103/0366-6999.211899,0,0,
1159,"No rubbing, no elastosis perforans serpiginosa",,acanthosis/di [Diagnosis];adult;case report;clinical feature;disease duration;drug efficacy;drug response;drug withdrawal;elastosis/di [Diagnosis];elastosis/dt [Drug Therapy];elastosis/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];female;human;kidney dysfunction/si [Side Effect];letter;liver cirrhosis;papule;skin biopsy;skin defect;treatment outcome;Wilson disease/dt [Drug Therapy];colecalciferol/dt [Drug Therapy];colecalciferol/tp [Topical Drug Administration];corticosteroid/dt [Drug Therapy];corticosteroid/tp [Topical Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration],"Ashida, M.;Okubo, Y.;Iwanaga, A.;Utani, A.",2017,August,http://dx.doi.org/10.1111/1346-8138.13874,0,0,
1160,Wilson's disease and diagnostic conundrum in a low income country,Wilson's disease is a well-known leading cause of chronic liver disease in children. However it may remain undiagnosed in a resource limited setting for a long period. We describe a six year male child diagnosed Wilson's disease with extreme elevation of liver enzymes which is not reported earlier. The diagnosis was also baffling because of inconsistency of other laboratory parameters. Copyright © Pratap Kumar Patra et al.,Diagnostic dilemma;Resource limited setting;Wilsons disease;abdominal pain;alanine aminotransferase blood level;albumin blood level;article;aspartate aminotransferase blood level;bilirubin blood level;case report;ceruloplasmin blood level;child;chronic liver disease/di [Diagnosis];decreased appetite;disease severity;eye discoloration;eye disease;follow up;globulin blood level;hepatomegaly/di [Diagnosis];human;human tissue;jaundice;leukocyte count;liver biopsy;low income country;male;nausea;pallor;physical examination;preschool child;prothrombin time;slit lamp;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline transferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];transferase/ec [Endogenous Compound];unclassified drug,"Patra, P. K.",2017,13 Apr,http://dx.doi.org/10.11604/pamj.2017.26.201.11377,0,0,
1161,Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive,"Objectives While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. Methods Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. Results The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. Conclusions Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education. Copyright © 2017 The Canadian Society of Clinical Chemists",Copper deficiency;Cytopenia;Denture adhesive;Myeloneuropathy;Zinc;adult;article;blood transfusion;bone marrow biopsy;case report;ceruloplasmin blood level;copper blood level;copper deficiency/di [Diagnosis];copper deficiency/dt [Drug Therapy];copper deficiency myeloneuropathy/di [Diagnosis];copper deficiency myeloneuropathy/dt [Drug Therapy];cytopenia/di [Diagnosis];cytopenia/dt [Drug Therapy];disease severity;dyspnea;fatigue;female;histology;human;human tissue;laboratory test;liver biopsy;macrocytic anemia;myelodysplastic syndrome/dt [Drug Therapy];myelodysplastic syndrome/th [Therapy];neuropathy/di [Diagnosis];neuropathy/dt [Drug Therapy];neutropenia;priority journal;reticulocyte count;spinal cord disease/di [Diagnosis];spinal cord disease/dt [Drug Therapy];staining;vitamin supplementation;Wilson disease;zinc blood level;adhesive agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cyanocobalamin/dt [Drug Therapy];unclassified drug;zinc/ec [Endogenous Compound];zinc containing denture adhesive/dt [Drug Therapy],"Cathcart, S. J.;Sofronescu, A. G.",2017,August,http://dx.doi.org/10.1016/j.clinbiochem.2017.03.005,0,0,
1162,Drosophila melanogaster models of metal-related human diseases and metal toxicity,"Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have many advantages in the laboratory, such as a short life cycle, easy handling and inexpensive maintenance. Furthermore, they can be raised in a large number. In addition, flies are greatly appreciated because they offer a considerable number of genetic tools to address some of the unresolved questions concerning disease pathology, which in turn could contribute to our understanding of the metal metabolism and homeostasis. This review recapitulates the metabolism of the principal transition metals, namely iron, zinc and copper, in Drosophila and the utility of this organism as an experimental model to explore the role of metal dyshomeostasis in different human diseases. Finally, a summary of the contribution of Drosophila as a model for testing metal toxicity is provided. Copyright © 2017 by the authors. Licensee MDPI, Basel, Switzerland.",atp7;Copper;Drosophila;DZip99C;Frataxin;Heavy metal toxicity;Iron;Metal homeostasis;Neurodegeneration;Zinc;Alzheimer disease;cell respiration;DNA damage;DNA synthesis;Drosophila melanogaster;Ehlers Danlos syndrome;Friedreich ataxia;gene control;gene mutation;genetic analysis;heavy metal poisoning;Huntington chorea;iron metabolism;lipid peroxidation;nerve degeneration;oxygen transport;Parkinson disease;review;translation initiation;Wilson disease;glutathione;iron regulatory factor;Menkes protein/ec [Endogenous Compound];presenilin,"Calap-Quintana, P.;Gonzalez-Fernandez, J.;Sebastia-Ortega, N.;Llorens, J. V.;Molto, M. D.",2017,06 Jul,http://dx.doi.org/10.3390/ijms18071456,0,0,
1163,Anaesthetic management in Wilson's disease with severe neuropsychiatric manifestations,"A 15 year-old girl presented with acute psychosis, seizures and right shoulder dislocation with an overlying abscess. The symptomatology was diagnosed to be due to Wilson's disease. The anaesthetic management and postoperative analgesia was a challenging task in presence of hepatic and acute neurological dysfunction as well as difficulty in pain assessment. There are only a few reported cases of anaesthetic management in patients with Wilson's disease with severe neuropsychiatric symptoms. This case portrays the safe use of both general and regional anaesthesia in such a patient. Copyright © 2017, College of Anaesthesiologists of Sri Lanka. All rights reserved.",Anaesthesia;Interscalene block;Neuro-psychiatric symptoms;Wilson's disease;abscess drainage;acute psychosis;adolescent;anesthesia induction;article;behavior disorder/dt [Drug Therapy];case report;choreoathetosis;clinical feature;disease severity;female;focal epilepsy;gait disorder;hospital admission;human;insomnia;mental disease;muscle hypertonia;open reduction (procedure);patient monitoring;patient safety;postoperative analgesia;postoperative pain/co [Complication];postoperative pain/dt [Drug Therapy];postoperative pain/pc [Prevention];seizure;shoulder abscess/su [Surgery];shoulder disease/su [Surgery];shoulder dislocation;slurred speech;symptomatology;tremor;Wilson disease/dt [Drug Therapy];atracurium besilate;bupivacaine/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];fentanyl/dt [Drug Therapy];isoflurane;levetiracetam/dt [Drug Therapy];nitrous oxide;paracetamol/dt [Drug Therapy];paracetamol/iv [Intravenous Drug Administration];penicillamine/dt [Drug Therapy];propofol;quetiapine/dt [Drug Therapy];risperidone/dt [Drug Therapy];thioridazine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy],"Nanjangud, P. R.;Prasad, S.",2017,,http://dx.doi.org/10.4038/slja.v25i2.8226,0,0,
1164,Delivery of Copper-chelating Trientine (TETA) to the central nervous system by surface modified liposomes,"The existence of the blood-brain barrier (BBB) complicates the treatment of many central nervous system (CNS) disorders, including the copper storage disease, Wilson's disease. Its CNS symptoms represent a serious problem, since therapeutics for Wilson's disease do not cross the BBB. One strategy to overcome this obstacle is the transfer of drugs across the BBB with colloidal carrier systems like liposomes. The aim of the present study was to encapsulate triethylenetetramine (TETA), a copper chelating agent, into surface modified liposomes and to investigate their permeation across the BBB. Liposomes were modified with cationized bovine serum albumin or penetratin, a cell penetrating peptide. Liposomes were characterized regarding size, PDI, zeta potential and encapsulation efficiency. Size was between 139.4 +/- 1.9 nm to 171.1 +/- 3.5 nm with PDI's below 0.2. Zeta potentials of vectorized liposomes were at least 6.9 mV higher than those of standard liposomes. Cryo-TEM micrographs displayed liposomal structure, integrity and the similarity of structure and size between loaded, unloaded, vectorized and non- vectorized liposomes. In vivo experiments in rats showed an up to 16-fold higher brain uptake of TETA in vectorized liposomes compared to free TETA or TETA in non-vectorized liposomes, proving successful brain delivery using target seeking surface modifications. Tissue analysis indicated TETA concentrations in the brain being high enough to treat Wilson's disease. Copyright © 2016",Apolipoprotein E;Blood brain barrier;Cationized albumin;Copper;Liposome;Penetratin;teta;Trientine;animal experiment;animal tissue;article;central nervous system;controlled study;drug clearance;drug uptake;encapsulation;freeze drying;in vivo study;isoelectric focusing;isoelectric point;liposomal delivery;male;nonhuman;polyacrylamide gel electrophoresis;priority journal;rat;static electricity;transmission electron microscopy;zeta potential;bovine serum albumin;iodine 131/iv [Intravenous Drug Administration];trientine/pr [Pharmaceutics];trientine/pk [Pharmacokinetics],"Tremmel, R.;Uhl, P.;Helm, F.;Wupperfeld, D.;Sauter, M.;Mier, W.;Stremmel, W.;Hofhaus, G.;Fricker, G.",2016,15 Oct,http://dx.doi.org/10.1016/j.ijpharm.2016.08.040,0,0,
1165,Chelation in metal intoxication-Principles and paradigms,"The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review. Copyright © 2014 Elsevier GmbH.",Deferasirox;Deferiprone;Deferoxamine;dmps;dmsa;arsenic poisoning/dt [Drug Therapy];autism/dt [Drug Therapy];binding affinity;chelation therapy;clinical effectiveness;clinical feature;drug absorption;drug excretion;drug fatality/si [Side Effect];drug half life;drug structure;drug tolerability;drug use;fever/si [Side Effect];headache/si [Side Effect];heart palpitation/si [Side Effect];heavy metal poisoning/dt [Drug Therapy];heavy metal poisoning/th [Therapy];human;hydrophilicity;hypertension/si [Side Effect];hypertransaminasemia/si [Side Effect];iron overload/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];maculopapular rash/si [Side Effect];nausea/si [Side Effect];nonhuman;priority journal;review;sweat gland disease/si [Side Effect];symptomatology;treatment response;unspecified side effect/si [Side Effect];vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];antimony;bismuth;deferasirox/ae [Adverse Drug Reaction];deferasirox/cb [Drug Combination];deferasirox/dt [Drug Therapy];deferasirox/po [Oral Drug Administration];deferasirox/pk [Pharmacokinetics];deferasirox/pd [Pharmacology];deferiprone/ae [Adverse Drug Reaction];deferiprone/cb [Drug Combination];deferiprone/dt [Drug Therapy];deferiprone/po [Oral Drug Administration];deferiprone/pk [Pharmacokinetics];deferiprone/pd [Pharmacology];deferoxamine mesylate/dt [Drug Therapy];deferoxamine mesylate/pk [Pharmacokinetics];deferoxamine mesylate/pd [Pharmacology];deferoxamine mesylate/sc [Subcutaneous Drug Administration];dimercaprol/cb [Drug Combination];dimercaprol/dt [Drug Therapy];edetate calcium disodium/ae [Adverse Drug Reaction];edetate calcium disodium/cb [Drug Combination];edetate calcium disodium/dt [Drug Therapy];edetate calcium disodium/iv [Intravenous Drug Administration];edetic acid/pk [Pharmacokinetics];edetic acid/pd [Pharmacology];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];succimer/ae [Adverse Drug Reaction];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];succimer/pa [Parenteral Drug Administration];succimer/pk [Pharmacokinetics];succimer/pd [Pharmacology];trientine/dt [Drug Therapy];trientine/iv [Intravenous Drug Administration];trientine/po [Oral Drug Administration];trientine/pk [Pharmacokinetics];trientine/pd [Pharmacology];unithiol/ae [Adverse Drug Reaction];unithiol/dt [Drug Therapy];unithiol/po [Oral Drug Administration];unithiol/pa [Parenteral Drug Administration];unithiol/pk [Pharmacokinetics];unithiol/pd [Pharmacology],"Aaseth, J.;Skaug, M. A.;Cao, Y.;Andersen, O.",2015,,http://dx.doi.org/10.1016/j.jtemb.2014.10.001,0,0,
1166,Obstetric Outcome in Women with Chronic Liver Disease,"Aim: This study determines the prevalence, causes and outcome of pregnancy in women with chronic liver diseases in a tertiary level teaching institute in Southern India. Methods: Retrospective analysis of case records was carried out between December 2010 and May 2015 in the departments of Obstetrics and Gynecology and Gastroenterology including pregnant women diagnosed to have chronic liver diseases prenatally or during pregnancy. Results: The frequency of chronic liver disease in pregnancy was 50 among 10,823 deliveries (0.4%). Twenty-six women with chronic liver disease had 50 pregnancies during the study period. Fifty percent of the women had cirrhosis. Maternal complications occurred in 22% of the study group. Variceal hemorrhage occurred in 4%, and hepatic decompensation occurred in 16%. There were two maternal deaths (4%). Obstetric complication such as preeclampsia, postpartum hemorrhage and puerperal infection occurred in 18, 14 and 18%, respectively. Abortion occurred in 34%, 55% in cirrhotic and 4.8% in non-cirrhotic. Live birth rate of 76% was significantly higher (p < 0.014) in the non-cirrhotic group compared to cirrhotic group. Conclusion: Pregnancies in chronic liver disease are associated with high rate of abortions. Live birth rates are better and complications such as variceal bleeding or decompensation of liver disease are less common than previously reported. Copyright © 2016, Federation of Obstetric & Gynecological Societies of India.",Chronic liver disease;Cirrhosis;Hepatic decompensation;Pregnancy;Variceal hemorrhage;adult;anemia;article;ascites;autoimmune hepatitis;birth rate;Budd Chiari syndrome;chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];chronic liver disease/ep [Epidemiology];clinical article;decompensated liver cirrhosis;endoscopic sclerotherapy;endoscopic surgery;esophagus varices;female;hepatitis B;human;hypersplenism;India;jaundice;live birth;maternal death;outcome assessment;portal hypertension;postpartum hemorrhage;pregnancy outcome;prevalence;priority journal;puerperal infection;retrospective study;thrombocytopenia;Wilson disease;azathioprine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];propranolol/dt [Drug Therapy];tenofovir/dt [Drug Therapy],"Jena, P.;Sheela, C. N.;Venkatachala, R. P.;Devarbhavi, H.",2017,01 Aug,http://dx.doi.org/10.1007/s13224-016-0959-y,0,0,
1167,"The pseudosclerotic form (""wing beating tremor"") of wilson's disease","Wilson disease is a rare monogenic, autosomal recessive disorder of cooper metabolism, leading to progressive accumulation of cooper in different organs, essentially in the liver, brain and cornea. We report a case of a 25 years old man, Caucasian, with ""wing-beating tremor"" in the right arm that started with two month in advance of hospital admission, than evolved to the left arm, a week before hospitalization. The slit-lamp examination showed the presence of Kayser-Fleischer rings in both eyes. The laboratory tests and brain MRI confi rmed the diagnostic of Wilson's disease.",Cooper metabolism;Wilson disease;Wing- beating tremor;article;blood cell count;clinical feature;disease association;drug dose increase;dysarthria;endoscopic echography;eye examination;follow up;functional neuroimaging;hospitalization;laboratory test;liver function test;nuclear magnetic resonance imaging;slit lamp;treatment outcome;tremor/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];wing beating tremor/dt [Drug Therapy];wing beating tremor;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];primidone/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Poalelungi, A.;Poalelungi, V.;Mladin, D.;Popescu, B. O.",2015,,,0,0,
1168,Liver transplantation for Wilson disease: Review and a case report of an unexpected neurological complication,"Wilson's disease is a rare autosomal recessive inherited disorder of copper metabolism, which results in copper accumulation in several tissues, especially with liver injury and failure. Orthotopic liver transplantation (OLT) can be lifesaving for patients with hepatic complications of Wilson's disease- fulminant liver failure or unresponsivness to medical therapy in chronic liver disease, with or without neurological manifestations. We report the case of a 19-year-old woman receiving a liver transplant for acute liver failure caused by Wilson's disease, who developed headache as the only symptom of a serious neurological complication after transplantation. The clinical course and neuroimaging demonstrating aneurismal subarachnoid hemorrhage are presented. The neurological complications and the difficulties of medical management in an immunosuppressed patient are discussed. Headache in a recently transplanted patient for acute liver failure may be a sign of a serious cerebral complication, subarachnoid hemorrhage. Early recognition and proper management may prevent life-threatening neurologic complications but chronic immunosuppression may impede a favourable outcome.",Acute liver failure;Liver transplantation;Subarachnoid hemorrhage;Wilson's disease;adult;anemia/si [Side Effect];aplastic anemia/si [Side Effect];brain artery aneurysm rupture;brain infarction;case report;cause of death;drug fever/si [Side Effect];female;fulminant hepatic failure/su [Surgery];gastritis/si [Side Effect];headache/dt [Drug Therapy];hemiplegia;human;hydrocephalus;immunopathology/si [Side Effect];immunosuppressive treatment;leukopenia/si [Side Effect];liver failure/su [Surgery];liver graft rejection/dt [Drug Therapy];liver toxicity/si [Side Effect];lupus like syndrome/si [Side Effect];nephrotic syndrome/si [Side Effect];neuroimaging;neutropenia/si [Side Effect];pancreatitis/si [Side Effect];review;sideroblastic anemia/si [Side Effect];thrombocytopenia/si [Side Effect];vasospasm/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];daclizumab/dt [Drug Therapy];nimodipine/dt [Drug Therapy];paracetamol/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];steroid/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Anghel, D.;Campeanu, A.;Popescu, I.;Matei, E.;Dorobantu, B.;Tomescu, D.;Popa, L.;Lupescu, I.;Tanasescu, R.",2012,,,0,0,
1169,Wilson's disease,"A disturbance of copper metabolism causes hepatolenticular degeneration (Wilson's disease), an autosomal recessive disorder whose genetic locus lies on the long arm of chromosome 13. The concentration of the copper transport protein ceruloplasmin is abnormally low and, as a result, the serum free copper concentration is high and an abnormally large amount of copper is eliminated in the urine. Free copper is deposited in the liver, the edge of the cornea, the brain. We present a case who debuted by tremors and thrombocytopenia. Continuous therapy with Trientine hydrochloride and Mega zinc, and elimination of copper rich foods were improved cognitive, behavioral and motor dysfunctions.",Global assessment scale for WD (GAS for WD);Treatment;Wilson's disease (WD);adult;article;autosomal recessive disorder;behavior disorder;case report;chromosome 13;cognitive defect;copper metabolism;gene locus;human;motor dysfunction;thrombocytopenia;tremor;urine;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Hancu, A.;Mihai, C.;Zguma, D.;Axelerad, A. D.;Dumitru, E.;Kaivanifard, M.",2011,,,0,0,
1170,Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease,"Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma. Copyright © 2016 INASL",Barcelona clinic liver cancer (BCLC) staging;cirrhosis;D-penicillamine;decompensation;abdominal distension;abdominal pain;adult;alpha fetoprotein blood level;anorexia;article;ascites;ascites fluid;case report;ceruloplasmin blood level;chemoembolization;clinical feature;computer assisted tomography;copper blood level;decompensated liver cirrhosis;diet therapy;disease duration;gastrointestinal hemorrhage;hepatography;human;jaundice;liver cell carcinoma/di [Diagnosis];liver cell carcinoma/th [Therapy];male;peritonitis;priority journal;rare disease;slit lamp microscopy;splenomegaly;weight reduction;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];alpha fetoprotein/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];carbidopa/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];levodopa/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Gunjan, D.;Shalimar;Nadda, N.;Kedia, S.;Nayak, B.;Paul, S. B.;Gamanagatti, S. R.;Acharya, S. K.",2017,June,http://dx.doi.org/10.1016/j.jceh.2016.09.012,0,0,
1171,"Late-Onset Wilson's disease, Dementia, Ekbom syndrome and whitte matter hyperintensities","Objective: The aim of this study is to describe a patient with late-onset Wilson's disease, dementia and Ekbom Syndrome. Background: Wilson's disease is an autosomal-recessive disorder due to a mutation in the ATP7B gene, causing impairment of biliary excretion of copper and its accumulation, first in the liver but ultimately in the brain and other tissues. Ekbom syndrome is characterized by a firm conviction by the patient that he/she is infested by parasites which come out of the skin, mouth, eyes or genital region. Methods: We report the case of a patient with an atypical presentations of Wilson's disease with Ekbom syndrome. Results: A 69 year-old man with chronic liver disease was referred to the Neurology group to investigate cognitive impairment, mostly executive complaints and deficits of episodic memory that had started 3 years previously. Neurological examination showed only flapping tremor. On follow-up the patient worsened and became agitated, aggressive and confused. After 6 months he started saying there were bugs moving through his skin, which were not observed by his relatives. Subsequently he developed extrapiramidal signs, with bradikynesia and muscle stiffness. Brain MRI showed diffuse white matter hyperintensities and cortical atrophy. Total serum ceruluplasmin was low in 2 occasions: 6.9 and 11. Ophthalmologic evaluation showed Kayser-Fleischer rings in both eyes. The diagnosis of Wilson's disease was made and D-penicilamine was initiated, without clinical response. Conclusions: Ekbom syndrome is normally related to psychiatric conditions or dementia, but its presence should raise the suspicion of other neurodegenerative disorders as it can appear before other classical signs. Although late-onset Wilson's disease is rare and usually doesn't present with initial dementia, it may have an atypical course. It should be included in the differential diagnosis work-up of dementia, especially because it is a potentially treatable if diagnosed in the early stages.",aged;biliary excretion;brain cortex atrophy;case report;chronic liver disease;cognitive defect;diagnosis;differential diagnosis;episodic memory;eye;female;flapping tremor;follow up;gene mutation;genital system;human;human tissue;male;mouth;muscle rigidity;neurologic examination;neurology;nonhuman;nuclear magnetic resonance imaging;parasite;relative;restless legs syndrome;skin;white matter;Wilson disease;endogenous compound;penicillamine;Wilson disease protein,"Germiniani, F.;Marques, P.;Zorzetto, F.;De Oliveira, L.;Teive, H.",2017,June,http://dx.doi.org/10.1002/mds.27087,0,0,
1172,Disappearance of the clinical and imaging manifestations in Wilson's disease after controlled therapy with tetrathiomolybdate and zinc,"Objective: To present a case with Wilson's disease (WD) whose neurological and imaging alterations disappeared after ammonium tetrathiomolybdate (AT) and zinc acetate (Zn) controlled therapy. Background: The treatment of Wilson's disease remains a challenge for clinicians. A strict control of the different copper pools is needed. Methods: Case report. Therapy control formula: ""Free"" serum copper (FC) = total serum copper - (serum ceruloplasmin x 3). De-coppering state: FC <10mug/dL. Copper deficiency: FC <5mug/dL Results: A 25-year-old woman presented a rapidly progressive tremor with severe functional impact of 1 year in duration. She had an asymptomatic chronic liver disease without portal hypertension. Physical exam: Bilateral Kayser-Fleischer rings and rest tremor in both upper limbs, both proximal and distal, of moderate amplitude. More significant tremor in both upper limbs appeared a few seconds after taking any antigravity posture, or simple action (""wing beating"" tremor). Once it appeared, was of increasing amplitude, and extended to the whole body, trunk, head and lower extremities. It would only disappear if she placed her upper limbs again in the rest position. Occasionally, dystonic right hand postures were observed. No other abnormalities. Investigations: Normal serum copper, elevated 24-hour urinary copper excretion and decreased serum ceruloplasmin. Normal liver function tests. She was compound heterozygote for mutations p.L1305P and p.H1069Q in ATP7B. Pretreatment brain MRI (figure 1A): Bilateral and symmetrical hypointensity in globus pallidus and substantia nigra and hyperintensity in putamen, lateral thalamus, central pons and dorsal midbrain. Initially, she was treated with D-penicillamine, Zn and vitamin B6, with worsening of the neurological symptoms and poor tolerance. D-penicillamine was withdrawn and started with AT. She had a spectacular improvement at 15 days of onset treatment, being asymptomatic at 4 months. She reached de-coppering state at 7 months of starting AT and it was removed, leaving only maintenance Zn (FC 5-10mug/dL). A 4-year post treatment brain MRI was normal (figure 1B). The patient remains asymptomatic after 8 years of follow-up. Conclusions: The association of AT+Zn as starting therapy and Zn as maintenance therapy were effective in the control of Wilson's neurological disease, through strict control of the different copper pools.",adult;body position;case report;ceruloplasmin blood level;chronic liver disease;congenital malformation;copper blood level;copper deficiency;dorsal region;drug therapy;dystonia;excretion;female;follow up;globus pallidus;gravity;hand;head;heterozygote;human;human tissue;liver function test;lower limb;maintenance therapy;mutation;nuclear magnetic resonance imaging;pons;portal hypertension;putamen;rest;substantia nigra;thalamus lateral nucleus;tremor;trunk;Wilson disease;endogenous compound;penicillamine;pyridoxine;tetrathiomolybdate ammonium;tetrathiomolybdic acid;Wilson disease protein;zinc;zinc acetate,"Posada, I.;Garfia, C.;Ostos, F.;Ramos, A.",2017,June,http://dx.doi.org/10.1002/mds.27087,0,0,
1173,"WTX101-a novel copper modulating agent for wilson disease demonstrates efficacy and safety in a phase 2, multi-center, open label study","Objective: The objective of this study was to evaluate the efficacy and safety of 24 week WTX101 treatment in newly diagnosed Wilson Disease (WD) patients. Background: WTX101 (bis-choline tetrathiomolybdate) is an investigational first in class copper modulating agent for the treatment of WD. Although WD therapies are available, substantial unmet medical needs exist with respect to efficacy, side effects and treatment convenience. Methods: Patients with WD aged > 18 years, treatment naive or treated for = 2 years with chelation or zinc therapy, initially received 15 or 30 mg WTX101 once daily. After 6 weeks, dosage was individually guided by laboratory and clinical criteria. Assessments included copper control, neurological and disability status using the Unified Wilson Disease Rating Scale (UWDRS), hepatic status and safety. Results: Twenty-eight patients entered the study. Baseline average non-ceruloplasmin copper (NCC) was elevated (3.6muM) and 23/28 had neurological manifestations (average UWDRS part 3 score 22.8). The primary endpoint of copper control was met in 79% of patients (p<0.001). Mean reduction of NCC levels was 77% (p<0.0001). Both neurological status (p<0.0001) and disability (p<0.001) improved as measured by UWDRS Parts 3 and 2, respectively. In addition, liver status, as measured by the Modified Nazer Score, was stabilized or improved in the majority of patients. Treatment with WTX101 was generally well tolerated with most reported adverse events being mild (grade 1) to moderate (grade 2). Reversible liver test elevations were observed in 39% of patients and these elevations were generally mild to moderate, asymptomatic and normalized with dose adjustments. No initial drug-induced neurological worsening was observed upon treatment initiation with WTX101. Conclusions: Once daily WTX101 treatment has the potential to rapidly lower and control free copper, and improve neurological status and disability in patients with WD. Additionally, WTX101 was generally well-tolerated with no observed cases of neurological worsening upon initiation of WTX101. Together with its simplified dosing, WTX101 has the potential to address the unmet needs in WD. Further clinical evaluation of WTX101 is warranted to establish its safety and efficacy for the treatment of WD.",adverse drug reaction;chelation;clinical evaluation;clinical trial;comparative effectiveness;controlled clinical trial;controlled study;diagnosis;disability;disease course;drug therapy;female;human;liver;major clinical study;male;normal human;open study;phase 2 clinical trial;rating scale;safety;side effect;Wilson disease;choline tetrathiomolybdate;zinc,"Bega, D.;Ala, A.;Askari, F.;Bronstein, J.;Czlonkowska, A.;Ferenci, P.;Nicholl, D.;Weiss, K. H.;Schilsky, M.",2017,June,http://dx.doi.org/10.1002/mds.27087,0,0,
1174,"Neurological worsening in patients undergoing treatment for Wilson's disease: Frequency, causes and outcomes","Objective: To study the pattern of neurological worsening (NW) in patients undergoing treatment for Wilson's disease (WD). Background: WD is an inherited disorder of copper metabolism. Treatment involves copper chelation and can reverse neurological disability and prevent disease-related mortality. However, some patients develop worsening of neurological signs during treatment. This can be drug-induced, or due to non-compliance, disease progression, intercurrent illnesses or emergent psychosis.a, b Methods: From 2005-2016 we prospectively recruited 120 consecutive patients visiting our Wilson's disease Clinic and tracked their neurological disability during treatment using Tier 2 of the Global Assessment Scale for Wilson disease (GAS for WD).b All received penicillamine (125-2000mg/day) except for 5 who were on trientine (300-1800mg/day). Results: Among the 120 patients (72 male; 48 female) we observed 64 instances of NW in 44 patients (30 male). The earliest signs of NW were irritability, or worsening of dysarthria, Wilson's facies or Kayser-Fleischer rings. Non-compliance with treatment was the commonest cause and was seen in 16 patients during the early intensive phase of copper chelation and in 18 patients during the maintenance phase. Most of these patients defaulted on treatment multiple times. Drug-induced NW was seen in 12 patients; 11 on penicillamine (mean dose 900mg; range 750-1750mg) and 1 on trientine (900mg). The time between initiation of treatment and NW varied widely (mean 2.8 months; range 0.5-14 months). In 10 patients such worsening was reversible over an average period of 1.2 months (range 0.5-4 months) with brief down-titration of the drug. However, in two it led to long term disability. NW due to disease progression was seen in four patients in the first few months of treatment initiation and improved with ongoing copper chelation. Emergent psychosis and intercurrent illnesses accounted for 11 and three cases of NW, respectively. These also improved with continued chelation. Conclusions: NW is seen over one-third of the patients undergoing treatment for WD with non-compliance being the most common cause. Monitoring neurological disability using GAS for WD scale enables one to detect such worsening, identify its cause, and respond appropriately (by encouraging compliance, down-titrating the dose, or continuing treatment course).",adverse drug reaction;chelation;clinical trial;disability;disease course;drug combination;drug dose titration;dysarthria;female;hospital;human;irritability;major clinical study;male;monitoring;morbidity;participant observation;psychosis;side effect;titrimetry;Wilson disease;penicillamine;trientine,"Aggarwal, A.;Bhatt, M.",2017,June,http://dx.doi.org/10.1002/mds.27087,0,1,
1175,Follow-up of liver steatosis and fibrosis in children with Wilson's disease using transient elastography (Fibroscan),"Objectives and study: Liver involvement in children with Wilson's disease ranges from simple steatosis, steatohepatitis to severe fibrosis. Pharmacological treatment is aimed to preserve liver function and improve patients' clinical condition. Transient elastography (Fibroscan Echosens, France) has been already applied in many chronic liver diseases for non-invasive assessment of liver stiffness/fibrosis and steatosis. We aimed to evaluate the change of liver stiffness/fibrosis and steatosis and selected laboratory markers of liver function over time in children with Wilson's disease using Fibroscan. Methods: We included 33 children (19 females) with mean age of 11.5yrs with Wilson's disease, treated with either zinc or d-penicillamine. Patients with acute liver failure were excluded. At the baseline and after a mean period of 1.5 yrs all patients underwent Fibroscan examinations with medium (M) probe to assess liver stiffness (E) and steatosis (Controlled Attenuation Parameter, CAP). Repeated laboratory liver function tests were performed at the same time. Wilcoxon test was used for statistical analysis. Results: At the baseline, our patients presented with slightly elevated liver enzymes ALT-49.5U/I (27.5-69), AST-34.5U/I (25.5-45.5), GGTP-26U/I (19.5-35.5) and well preserved liver function INR-1.1 (1.05-1.16) [median, lower, upper quartile]. Initial Fibroscan examination showed normal median liver stiffness 4.4kPa (M probe) (4.0-5.4) and slightly elevated liver steatosis CAP-257dB/m (235-283) [median, lower, upper quartile]. After a period of 1.5 years we found decrease, but not statistically significant, in ALT, AST and INR in our patients. Only GGTP was significantly lower than the baseline results (p=0.02). Similarly we have not observed marked difference in liver steatosis (CAP) or liver stiffness by Fibroscan when compared baseline and repeated measurements. Conclusion: 1. Liver stiffness/fibrosis and steatosis seem not to significantly improve in the short-term followup observation period of children with Wilson's disease, as based on the Fibroscan measurements. 2. Transient elastography (Fibroscan) can be easily used in children with Wilson's disease for monitoring of liver stiffness/fibrosis and steatosis.",acute liver failure;attenuation;child;clinical article;clinical trial;elastograph;fatty liver;female;fibrosis;follow up;human;hypertransaminasemia;international normalized ratio;liver function test;liver stiffness;monitoring;rank sum test;school child;transient elastography;Wilson disease;endogenous compound;gamma glutamyltransferase;penicillamine;zinc,"Janczyk, W.;Dadalski, M.;Socha, P.",2017,April,http://dx.doi.org/10.1097/01.mpg.0000516381.25680.b4,0,1,
1176,The first study of Wilson's disease prevalence in a Portuguese population,"Objectives and study: Wilson's Disease (WD) is a rare autosomal recessive disorder responsible for an anomalous tissue deposition of copper. Global prevalence is estimated to be 1:40.000 although recent studies suggest possible underdiagnosis. There is an absence of studies regarding epidemiologic information of WD in Portugal. The primary goal of the study was estimating disease prevalence and incidence. Secondary goals focused on a descriptive analysis of the main clinical, pathological and biochemical characteristics of WD course in this population. Methods: Study design was retrospective, and included WD patients of all ages, observed between 1995 and 2015, with a minimum follow-up of 3 months and confirmed to have been born in the Northern region of Portugal. Patients were identified through the use of the Portuguese National Health Service's clinical coding system based on clinical data of thirteen Portuguese hospitals, liver biopsy histological assessment and hospital prescription records. Statistical analysis was conducted to establish potential clinical-analytical correlations through chi square, Mann-Whitney U, Friedman and Wilcoxon tests. Results: We identified and collected clinical data on 94 WD patients, six of which were deceased. Prevalence of WD in the past 20 years was 1:37.000 with a current prevalence of 1 per 45.000 inhabitants and an incidence of 1 per million people/year. A pediatric age of presentation occurred in 55,8% with a median age at diagnosis of 16,6 years (12,3-20,8) and male gender in 53,2%. Average follow-up was 15,2+/-8,8 years. Predominant liver disease was the most common form of presentation in 54,8%, with 37,0% of these presenting with cirrhosis; mixed neurological/hepatic symptoms in 17,9% and predominant neurological presentation in 10,7%. Neurological symptoms were associated with a later disease onset (p=0,001) and higher presence of Kayser-Fleischer rings (p<0,001), detected in 27,0% of all patients. Liver transplant was accomplished in 23,9%. Regarding therapy, penicillamine was the most frequently used, with adverse reactions observed in 24,8% and trientine was used in 41,0% patients at some moment of the disease. A significant reduction in hepatic liver enzymes was observed 6 and 12 months after starting therapy (AST: p=0,002; ALT:p=0,002), which was not observed in urinary copper excretion. Conclusion: This study constitutes a step further in a better comprehension of epidemiological, clinical and disease management of WD in the Northern Portuguese region, which appears similiar to previously published works in other countries. Since more than half of WD patients were diagnosed at a paediatric age, efforts should be focused on development of tools directed to the establishment of an early diagnosis for a better disease management.",adverse drug reaction;child;clinical trial;coding;comprehension;diagnosis;disease duration;early diagnosis;excretion;female;follow up;gender;hospital;human;information processing;liver biopsy;liver cirrhosis;liver graft;major clinical study;male;national health service;neurologic disease;Portugal;Portuguese (citizen);prescription;prevalence;rank sum test;side effect;study design;Wilson disease;liver enzyme;penicillamine;trientine,"De Sousa, B. R. R. M.;Antunes, H.",2017,April,http://dx.doi.org/10.1097/01.mpg.0000516381.25680.b4,0,1,
1177,Disorders in Hepatic Copper Secretion: Wilson's Disease and Pleomorphic Syndromes,"Wilson's disease (WD) is a rare disease the prevalence of which is higher than previously thought. Caused by genetic variations that target the copper (Cu) transporting P-ATPase Atp7b and disrupt the elimination of Cu by the liver, Atp7b truncations are associated with early severe liver disease and missense mutations with the late presentation of neurologic disorders. The asymptomatic initiation and false unimportance of initial symptoms often delays the crucial early diagnosis and a treatment that is lifesaving. The occasional acute liver failure persistently threatens the life of patients with WD. The gravity and progression of the disease are strongly dependent on the genetic background that organizes the response to the oxidative damage produced by the raised levels of free Cu. In this review, the authors focus on the prevalence, genetics, pathogenesis, clinical presentation, and treatment options in WD. They also discuss the new association of cuprotoxicosis with pleomorphic syndromes, of which MEDNIK is the first example, produced by genetic variations that disrupt the universal mechanisms of protein transport and thus perturb the traffic of Atp7b linked to Cu excretion. Copyright © 2017 by Thieme Medical Publishers, Inc.",Atp7b;copper;liver;toxicosis;acute liver failure;article;clinical feature;disease course;early diagnosis;genetic background;genetic variation;genetics;human;intoxication;missense mutation;prevalence;priority journal;protein transport;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];chelating agent/dt [Drug Therapy];copper chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Lalioti, V.;Tsubota, A.;Sandoval, I. V.",2017,01 May,http://dx.doi.org/10.1055/s-0037-1602764,0,0,
1178,Wilson disease,"Purpose of Review: This article reviews the clinical features of Wilson disease, focusing on the neurologic and psychiatric abnormalities, and addresses the diagnostic workup and treatment approaches to managing the disease. Recent Findings: The list of known mutations causing Wilson disease continues to grow, but advances in genetic testing may soon make it feasible to routinely perform genetic testing on individuals suspected of having Wilson disease. Summary: Wilson disease is a rare genetic disorder with protean manifestations that should be considered in the differential diagnosis of any individual presenting with unexplained neurologic, psychiatric, or hepatic dysfunction. Appropriate diagnostic testing should be expeditiously performed and treatment promptly initiated and maintained since failure to diagnose and treat Wilson disease will result in progressive and ultimately irreversible damage to the neurologic and other systems. Copyright © 2016 American Academy of Neurology.",acute hepatitis;ascites;autonomic dysfunction;brain depth stimulation;ceruloplasmin blood level;clinical feature;copper blood level;depression;diagnostic error;diet therapy;differential diagnosis;dysphagia;esophagus varices;eye disease;fracture;fulminant hepatic failure;genetic screening;headache;hemolytic anemia;human;liver biopsy;liver cirrhosis;liver dysfunction;liver transplantation;mental disease;neuroimaging;neurologic disease;osteoporosis;paranoia;patient monitoring;practice guideline;review;seizure;slit lamp microscopy;splenomegaly;suicidal behavior;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Pfeiffer, R. F.",2016,,,0,0,
1179,Atypical clinical and radiological features of Wilson's disease,"Introduction: Wilson's disease (WD) is an inherited disorder of copper metabolism causing hepatic, neurological and other systemic manifestations. The diagnosis must be considered in a young patient with chronic liver disease and neurological manifestations. Case report: In our case, a young male presented with insidious and gradually progressive difficulty in walking and sitting. On examination, patient had stuporous look and was unable to vocalize. On motor examination, dystonia and exaggerated deep reflexes (Figure Presented) were present. The Kayser-Fleischer ring was visible on both sides by the naked eye. His serum ceruloplasmin was decreased, serum copper level slightly raised and his 24 hours urine copper excretion was increased to about 10 times the normal value. His USG abdomen showed liver with coarse altered echo. On MRI of brain, there was ""giant panda face appearance"" with white matter abnormalities (Figure 1). Discussion: Wilson's disease (WD) is an autosomal recessive inborn error of the copper metabolism caused by a mutation in the gene, ATP7B. In Wilson's disease with neurological presentations, the sympatomatology is predominantly extra-pyramidal, like dystonia, tremors, dysphasia, dysarthria and ataxia. Our case had neurological manifestations, predominantly dystonia, dysarthria and cognitive impairment. MRI brain showed involvement of white matter in bilateral frontal cortex along with typical features as seen in Wilson disease. These white matter abnormalities are rare and have been infrequently reported. Our patient was treated with zinc due to non-availability of trientine and tetrathiomolybdate, and showed improvements in neuropsychiatric aspects. Conclusion: A high index of suspicion is required while dealing with adolescents and young adults with abnormal movements and neurobehavioral abnormalities. A high degree of suspicion and an early detection of WD are critical, because its diagnosis can be easily missed, but if diagnosed in early stages and treated appropriately, patient can have a normal life.",abdomen;adolescent;adult;ataxia;case report;ceruloplasmin blood level;chronic liver disease;cognitive defect;congenital malformation;copper blood level;copper metabolism;diagnosis;drug therapy;dysarthria;dyskinesia;dysphasia;dystonia;excretion;frontal cortex;gene mutation;genetic predisposition;human;human tissue;male;normal value;nuclear magnetic resonance imaging;reflex;tremor;urine;walking difficulty;white matter;Wilson disease;young adult;endogenous compound;tetrathiomolybdic acid;trientine;Wilson disease protein;zinc,"Goyal, S.;Dabla, S.;Sharma, B.;Yadav, K.",2015,June�July,http://dx.doi.org/10.1016/j.jceh.2015.07.158,0,0,
1180,Trientine dihydrochloride encapsulated nanoparticles for copper chelation therapy in rat model of non-wilsonian brain copper toxicosis,"Trientine is unable to mitigate the brain copper overload and neurological manifestations in Wilson's disease patients. The aim of this study was to assess the therapeutic efficacy of orally administered Trientine loaded nanoparticles to that of conventional Trientine for 90 days in Wistar rat model for non-Wilsonian brain copper toxicosis. High performance liquid chromatography, atomic absorption spectrophotometry, biochemical estimations, neurobehavioral and histopathological studies, and nanoparticles preparation and their physicochemical characterization were carried out. Trientine nanoparticles exhibited mean 351 nm size and less than 34% of Trientine release. Pharmacokinetics studies showed augmented levels of Trientine in brain of nanoparticles based Trientine delivery group compared to conventional Trientine delivery group. Conventional and nanoparticles based Trientine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary Cu levels, and acetylcholinesterase activity in rat model of Cu toxicosis. Conventional Trientine therapy resulted in negative rhodanine staining of liver and brain sections corroborated by 63%, and 16% reduction in hepatic and brain copper content, respectively compared to non-treated Cu-intoxicated group. However, liver and brain sections of nanoparticles based Trientine therapy group demonstrated grade 1 copper, and no copper depositions substantiated by 46% and 28% reduction in hepatic and brain copper content, respectively in comparison to non-treated copper-intoxicated group. Taken together, the present study reveals the first in vivo evidence for therapeutic efficacy of Trientine nanoparticles in chelating more brain copper and alleviating neurological deficits even at half the dose as given in conventional Trientine therapy.",animal experiment;animal model;atomic absorption spectrometry;brain;chelation therapy;controlled study;coordination;disease model;high performance liquid chromatography;histopathology;intoxication;liver;memory;nonhuman;oral drug administration;pharmacokinetics;physicochemical model;rat;rat model;staining;Wistar rat;acetylcholinesterase;endogenous compound;nanoparticle;rhodanine;trientine,"Pal, A.;Vasishta, R. K.;Thapa, B.;Prasad, R.",2014,March,,0,0,
1181,Spatial investigation of the elemental distribution in Wilson's disease liver after D-penicillamine treatment by LA-ICP-MS,"At present, the copper chelator D-penicillamine (DPA) is the first-line therapy of Wilson's disease (WD), which is characterized by an excessive copper overload. Lifelong DPA treatments aim to reduce the amount of detrimental excess copper retention in the liver and other organs. Although DPA shows beneficial effect in many patients, it may cause severe adverse effects. Despite several years of copper chelation therapy, discontinuation of DPA therapy can be linked to a rapidly progressing liver failure, indicating a high residual liver copper load. In order to investigate the spatial distribution of remaining copper and additional elements, such as zinc and iron, in rat and human liver samples after DPA treatment, a high resolution (spotsize of 10 mum) laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method was applied. Untreated LPP<sup>-/-</sup> rats, an established animal model for WD, appeared with a high overall copper concentration and a copper distribution of hotspots distributed over the liver tissue. In contrast, a low (>2-fold decreased) overall copper concentration was detected in liver of DPA treated animals. Importantly, however, copper distribution was highly inhomogeneous with lowest concentrations in direct proximity to blood vessels, as observed using novel zonal analysis. A human liver needle biopsy of a DPA treated WD patient substantiated the finding of an inhomogeneous copper deposition upon chelation therapy. In contrast, comparatively homogenous distributions of zinc and iron were observed. Our study indicates that a high resolution LA-ICP-MS analysis of liver samples is excellently suited to follow efficacy of chelator therapy in WD patients. Copyright © 2017 Elsevier GmbH",Copper;D-penicillamine;Elemental bioimaging;Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS);Wilson's disease;Zonal analysis;animal tissue;article;blood vessel;calibration;chelation therapy;controlled study;elemental analysis;human;human tissue;laser surgery;liver biopsy;liver tissue;mass spectrometry;nonhuman;priority journal;rat;tissue distribution;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Hachmoller, O.;Zibert, A.;Zischka, H.;Sperling, M.;Groba, S. R.;Grunewald, I.;Wardelmann, E.;Schmidt, H. H. J.;Hartmut, H. J.",2017,December,http://dx.doi.org/10.1016/j.jtemb.2017.05.008,0,0,
1182,Wilson's Disease in China,"Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. Its incidence is higher in China than in western countries. ATP7B is the causative gene and encodes a P-type ATPase, which participates in the synthesis of holoceruloplasmin and copper excretion. Disease-causing variants of ATP7B disrupt the normal structure or function of the enzyme and cause copper deposition in multiple organs, leading to diverse clinical manifestations. Given the variety of presentations, misdiagnosis is not rare. Genetic diagnosis plays an important role and has gradually become a routine test in China. The first Chinese spectrum of disease-causing mutations of ATP7B has been established. As a remediable hereditary disorder, most WD patients have a good prognosis with an early diagnosis and chelation treatment. However, clinical trials are relatively few in China, and most treatments are based on the experience of experts and evidences from other countries. It is necessary to study and develop appropriate regimens specific for Chinese WD patients. Copyright © 2017, Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore.",Copper;Epidemiology;Management;Pathogenesis;Wilson's Disease;ceruloplasmin blood level;China;clinical feature;gene mutation;genetics;human;laboratory test;neuroimaging;nonhuman;nuclear magnetic resonance imaging;review;systematic review (topic);Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];succimer/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Xie, J. J.;Wu, Z. Y.",2017,01 Jun,http://dx.doi.org/10.1007/s12264-017-0107-4,0,0,
1183,CURRENT ASPECTS OF WILSON'S DISEASE. [French],,"carbamates;ceruloplasmin;diagnosis;diet therapy;dimercaprol;drug therapy;genetics, human;hepatolenticular degeneration;penicillamine;diet;human;medical genetics;oxidation reduction reaction;Wilson disease;carbamic acid derivative;ester","Petit, H.",1964,01 Oct,,0,0,
1184,Trace element research-historical and future aspects,"During the last 30 years the International Society for Trace Element Research and the Nordic Trace Element Society has been active . During this period the importance of these elements for human diseases has been increasingly recognized, including their contribution to the global burden of disease. New analytical methods allow biomonitoring data to be related to health outcome. Future research using modern chemical methods will focus more on elemental speciation and on measuring lower concentrations leading to further identifying adverse effects and critical organs. Extensive knowledge about essentiality and toxicity of trace elements in humans has emerged during the last two decades and at present the difficulties in defining a range of acceptable oral intakes for essential elements has largely been overcome. Biological monitoring of trace element concentrations in various media such as blood or urine is of great importance and an overview is given. As an example, a more detailed description of biological monitoring of cadmium is given, explaining biokinetics including the role of metallothionein in modifying kinetics and toxicity. Finally future challenges related to risk assessment of newly developed metallic nanomaterials and metal containing medical devices are discussed. Copyright © 2016 Elsevier GmbH",Biological monitoring;Biomonitoring;Cadmium;Essentiality;Global burden of disease;Metallothionein;Toxicity;analytic method;blood analysis;copper metabolism;dietary reference intake;food intake;goiter;hair analysis;heavy metal poisoning;hemochromatosis;hereditary hemochromatosis;human;iodine deficiency;iron deficiency anemia;iron overload;lead poisoning;medical research;Menkes syndrome;nonhuman;priority journal;protein blood level;protein function;review;risk assessment;toxicity testing;urinalysis;Wilson disease;zinc deficiency;aluminum/to [Drug Toxicity];antimony/to [Drug Toxicity];arsenic/to [Drug Toxicity];cadmium/to [Drug Toxicity];chromium/to [Drug Toxicity];cobalt/to [Drug Toxicity];copper;iron/to [Drug Toxicity];lead/to [Drug Toxicity];metallothionein/ec [Endogenous Compound];methylmercury/to [Drug Toxicity];molybdenum/to [Drug Toxicity];nanomaterial;nickel/to [Drug Toxicity];selenium/to [Drug Toxicity];tin/to [Drug Toxicity];trace element/to [Drug Toxicity];vanadium/to [Drug Toxicity];zinc/to [Drug Toxicity],"Nordberg, M.;Nordberg, G. F.",2016,01 Dec,http://dx.doi.org/10.1016/j.jtemb.2016.04.006,0,0,
1185,"Efficacy and safety of a novel copper modulating agent (WTX-101) for Wilson Disease: Results of a phase 2, multi-center, open label study","Objective: The aim of this study was to evaluate the efficacy and safety of WTX101 in patients. newly diagnosed WD Background: WTX101 (bis-choline tetrathiomolybdate) is a novel copper modulating agent in development for treatment of Wilson Disease (WD). Although WD treatments are available, significant unmet medical needs exist with respect to efficacy, side effects and dosing simplicity. Design/Methods: Patients with WD aged > 18 years, treatment naive or treated for < 2 years with chelation or zinc therapy, initially received 15 or 30 mg WTX101 QD. After 6 weeks dosage was individually guided by laboratory and clinical criteria. Assessments over 24 weeks included neurological and daily activity status using the Unified Wilson Disease Rating Scale (UWDRS), hepatic status, copper parameters and safety. Results: Twenty-eight patients entered the study. Baseline average non-ceruloplasmin copper (NCC) was elevated (3.5uM), 23/28 had neurological manifestations (average UWDRS part III score 22), and all had hepatic involvement. Final results will be presented at the AAN Annual Meeting 2017. Preliminary data indicate that overall neurological (UWDRS part III) and daily activity (UWDRS part II) scores improved in patients with neurological manifestations. Hepatic status largely stabilized or improved. NCC (adjusted for molybdenum) decreased over time on treatment. Other Cu measurements (exchangeable Cu, total serum Cu, 24-hour urinary Cu excretion) indicate a similar de-coppering pattern. Overall WTX101 was well tolerated. Adverse events included reversible elevated liver tests in approximately 30% of patients and neutropenia. Conclusions: Once daily WTX101 treatment over 24 weeks improved neurologic disease, hepatic status and copper control in newly diagnosed WD patients. WTX101 appears well tolerated. Drug induced, paradoxical, neurological deterioration was not observed. Further clinical evaluation of WTX101 is warranted to establish its safety and efficacy for the treatment of WD.",adverse drug reaction;chelation;clinical evaluation;clinical trial;comparative effectiveness;controlled clinical trial;controlled study;daily life activity;diagnosis;drug therapy;excretion;female;human;human tissue;liver;major clinical study;male;neutropenia;open study;pharmacokinetics;phase 2 clinical trial;rating scale;safety;side effect;Wilson disease;choline tetrathiomolybdate;molybdenum;zinc,"Bega, D.;Ala, A.;Askari, F.;Bronstein, J.;Czlonkowska, A.;Ferenci, P.;Nicholl, D.;Weiss, K. H.;Schilsky, M.",2017,,,0,0,
1186,"Late-onset wilson's disease, dementia, ekbom syndrome and whitte matter hyperintensities","Objective: The aim of this study is to describe a patient with late-onset Wilson's disease, dementia and Ekbom Syndrome. Background: Wilson's disease is an autosomal-recessive disorder due to a mutation in the ATP7B gene, causing impairment of biliary excretion of copper and its accumulation, first in the liver but ultimately in the brain and other tissues. Ekbom syndrome is characterized by a firm conviction by the patient that he/she is infested by parasites which come out of the skin, mouth, eyes or genital region. Design/Methods: We report the case of a patient with an atypical presentations of Wilson's disease with Ekbom syndrome. Results: A 69 year-old man with chronic liver disease was referred to the Neurology group to investigate cognitive impairment, mostly executive complaints and deficits of episodic memory that had started 3 years previously. Neurological examination showed only flapping tremor. On follow-up the patient worsened and became agitated, aggressive and confused. After 6 months he started saying there were bugs moving through his skin, which were not observed by his relatives. Subsequently he developed extrapiramidal signs, with bradikynesia and muscle stiffness. Brain MRI showed diffuse white matter hyperintensities and cortical atrophy. Total serum ceruluplasmin was low in 2 occasions: 6.9 and 11. Ophthalmologic evaluation showed Kayser-Fleischer rings in both eyes. The diagnosis of Wilson's disease was made and D-penicilamine was initiated, without clinical response. Conclusions: Ekbom syndrome is normally related to psychiatric conditions or dementia, but its presence should raise the suspicion of other neurodegenerative disorders as it can appear before other classical signs. Although late- onset Wilson's disease is rare and usually doesn't present with initial dementia, it may have an atypical course. It should be included in the differential diagnosis work-up of dementia, especially because it is a potentially treatable if diagnosed in the early stages.",aged;biliary excretion;brain cortex atrophy;case report;chronic liver disease;cognitive defect;diagnosis;differential diagnosis;episodic memory;eye;female;flapping tremor;follow up;gene mutation;genital system;human;human tissue;male;mouth;muscle rigidity;neurologic examination;neurology;nonhuman;nuclear magnetic resonance imaging;parasite;relative;restless legs syndrome;skin;white matter;Wilson disease;endogenous compound;penicillamine;Wilson disease protein,"Marques, P.;Larissa, B.;Germiniani, F.;Teive, H. A.;Zorzetto, F.",2017,,,0,0,
1187,Copper deficiency in patient with prior diagnosis of AIDP,"Objective: To report case of Copper deficiency in setting of prior reported AIDP Background: Copper deficiency (CD) has been recognized to cause myelopathy, peripheral neuropathy and hematological abnormalities. Its known causes are enteropathies, zinc ingestion and gastric surgery, with approximately 20% of cases having no known etiology. Design/Methods: Case Report Results: A 32 year old female with history of AIDP presented with ascending weakness, numbness, pancytopenia, and on arrival loss of bowel and bladder function. Her exam found gross paraplegia and hypoesthesias below T3 level, with unique delayed ascending myotonic response with patellar stimulation. The patient also described rapid loss of tooth enamel in the months prior, gross peripheral ataxia, and labile affect. With a history of AIDP, a 5 days of IV methylprednisolone was started. Towards the end of her course of IV steroids she was found to have multiple nutritional deficiencies namely: thiamine, copper, and folate. Her exam improved, though a cause remained unclear. After the course of steroids was completed, plasmapharesis was started. The issue of low ceruloplasmin in the setting of low copper briefly brought Wilson's disease into the differential, specifically halting copper supplementation until being ruled out by 24 hour copper excretion. In the interim plasmapheresis -known to reduce circulating copper - was continued for possible CIDP treatment. Once Wilson's disease was ruled out, copper supplementation was restarted at 8mg daily depicting a mild improvement in symptoms and anemia leading to subsequent discharge. Conclusions: The presentation of CD imitating a Chronic inflammatory demyelinating radiculopathy, particularly in setting of prior AIDP, proved challenging in diagnosis and treatment. Where the initial positive response to steroids and plasmapheresis suggested an inflammatory etiology, the later ebb and flow suggested otherwise. The question remains whether initial episode of AIDP in the year prior was in fact the initial presentation of said CD vs CIDP.",acute inflammatory demyelinating polyneuropathy;adult;ataxia;bladder function;case report;chronic inflammatory demyelinating polyneuropathy;copper deficiency;diagnosis;drug therapy;enamel;enteropathy;excretion;female;human;hypesthesia;ingestion;intestine function;loss of function mutation;myotonia;pancytopenia;paraplegia;patella;periodontal disease;peripheral neuropathy;plasmapheresis;radiculopathy;spinal cord disease;stomach surgery;symptom;weakness;Wilson disease;ceruloplasmin;endogenous compound;folic acid;steroid;thiamine;zinc,"Upadhyaya, P.;Ghodsianzadeh, F.;Romero, R.;Bhavaraju-Sanka, R.",2017,,,0,0,
1188,Non-Wilsonian hepatolenticular degeneration: Clinical and MRI observations in four families from south India,"Non-Wilsonian hepatolenticular degeneration (NWHD) is a heterogeneous neurological disorder occurring secondary to chronic acquired liver disease. Genetically determined familial NWHD is rare, poorly understood, and often mistaken for Wilson's disease (WD). We analysed clinical and MRI profiles of NWHD patients who did not have obvious cause for acquired liver disease, such as alcohol intake or hepatitis. Six patients from four families (four males, two females, mean age: 17.0 +/- standard deviation 7.9 years), presenting with chronic extrapyramidal disorder resembling WD and imaging (abdominal ultrasound/MRI) evidence of cirrhosis were studied. They lacked Kayser-Fleischer rings or biochemical and/or genetic evidence of WD. Clinical features included dystonia (n = 6), parkinsonism (n = 3), tremor (n = 1), cerebellar ataxia (n = 3), orofacial dyskinesia (n = 1), behavioural abnormalities (n = 3), and cognitive decline (n = 1). Brain MRI revealed T1-weighted hyperintensity in the pallidum (n = 6), crus cerebri (n = 4), putamen (n = 1), caudate (n = 1), thalamus (n = 1), and red nucleus (n = 1) with T2-weighted shortening in some of these regions. Additional findings included giant cisterna magna (n = 1), face of giant panda sign (n = 1) and thin corpus callosum (n = 1). Areas of ""blooming"" on susceptibility weighted images were noted in two patients in the caudate (n = 2) and putamen (n = 1). The finding of T1 shortening is distinct from that of WD where the majority of lesions are T1-hypointense and T2-hyperintense. Extrapallidal T1-hyperintensity is also an exceptional observation in NWHD. The MRI appearance of intense T1 shortening coupled with the lack of increased susceptibility changes suggests that the most likely mineral deposited is manganese. The association of this neurological disorder and cirrhosis of the liver in the absence of an acquired liver disease is a distinct disease entity. This syndrome may represent a disorder of manganese metabolism resulting in its toxic deposition. Copyright © 2015 Elsevier Ltd.",Liver dysfunction;Manganese;mri;Non-Wilsonian hepatolenticular degeneration;Pallidal hyperintensity;Wilson's disease;adolescent;adult;article;ataxia/dt [Drug Therapy];behavior disorder;bone marrow biopsy;caudate nucleus;cerebellar ataxia;cerebral crus;child;cisterna magna;clinical article;clinical feature;cognitive defect;corpus callosum;degenerative disease;disease duration;disease exacerbation;dystonia;face of giant panda sign;female;gait disorder;globus pallidus;health care cost;hematemesis;hepatosplenomegaly;human;human tissue;India;joint swelling;laboratory test;liver disease;male;mental disease;muscle biopsy;neuroimaging;non Wilsonian hepatolenticular degeneration;nuclear magnetic resonance imaging;orofacial dyskinesia;parkinsonism/dt [Drug Therapy];priority journal;putamen;radiological parameters;recurrent disease;red nucleus;school child;thalamus;tremor/dt [Drug Therapy];alanine/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];amantadine/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];beta n acetylhexosaminidase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];clonazepam/dt [Drug Therapy];copper/ec [Endogenous Compound];levodopa/dt [Drug Therapy];parathyroid hormone/ec [Endogenous Compound];penicillamine;propranolol/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc sulfate,"Nagappa, M.;Sinha, S.;Saini, J. S.;Kallolimath, P.;Singh, N.;Kumar, A.;Bindu, P. S.;Taly, A. B.",2016,01 May,http://dx.doi.org/10.1016/j.jocn.2015.06.035,0,0,
1189,EASL Clinical Practice Guidelines: Wilson's disease,"This Clinical Practice Guideline (CPG) has been developed to assist physicians and other healthcare providers in the diagnosis and management of patients with Wilson's disease. The goal is to describe a number of generally accepted approaches for diagnosis, prevention, and treatment of Wilson's disease. Recommendations are based on a systematic literature review in the Medline (PubMed version), Embase (Dialog version), and the Cochrane Library databases using entries from 1966 to 2011. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system used in other EASL CPGs was used and set against the somewhat different grading system used in the AASLD guidelines (Table 1A and B). Unfortunately, there is not a single randomized controlled trial conducted in Wilson's disease which has an optimal design. Thus, it is impossible to assign a high or even a moderate quality of evidence to any of the questions dealt with in these guidelines. The evaluation is mostly based on large case series which have been reported within the last decades. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",abortion/si [Side Effect];acute liver failure/co [Complication];adjuvant therapy;ageusia/si [Side Effect];aminoaciduria;amylase blood level;anorexia;aplasia/si [Side Effect];article;ascites;ataxia;bioaccumulation;bleeding tendency;bone marrow depression/si [Side Effect];bone marrow toxicity/si [Side Effect];brain dysfunction/si [Side Effect];breast feeding;cardiomyopathy;central serous retinopathy/si [Side Effect];ceruloplasmin blood level;chelation therapy;cholestasis;chondrocalcinosis;chronic hepatitis;clinical trial (topic);Cochrane Library;computer assisted tomography;contraception;differential diagnosis;disease association;disease exacerbation/si [Side Effect];Doppler echography;drug dose reduction;drug withdrawal;elastosis/si [Side Effect];Embase;genetic screening;gigantism;Goodpasture syndrome/si [Side Effect];HELLP syndrome;hematuria/si [Side Effect];hemolysis;hemolytic anemia;hemosiderosis/si [Side Effect];hepatomegaly;histochemistry;human;hypercalciuria;immunoassay;immunoglobulin A deficiency/si [Side Effect];impulsiveness;infertility;jaundice;kidney calcification;lichen planus/si [Side Effect];literature;liver biopsy;liver cirrhosis;liver hemosiderosis/si [Side Effect];liver histology;liver necrosis;liver parenchyma;liver toxicity/si [Side Effect];liver transplantation;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];Medline;mental deterioration;mental disease;mutational analysis;myasthenia gravis/si [Side Effect];myopathy;nephrolithiasis;nephrotoxicity/si [Side Effect];neurologic disease;neuroradiology;neutropenia/si [Side Effect];nonalcoholic fatty liver;nuclear magnetic resonance imaging;osteoarthritis;pancreatitis;Parkinson disease;personality disorder;polymyositis/si [Side Effect];portal hypertension;postoperative complication/co [Complication];practice guideline;pregnancy;priority journal;prognosis;proteinuria/si [Side Effect];rash/si [Side Effect];side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];siderosis/si [Side Effect];single photon emission computer tomography;slit lamp;splenomegaly;spontaneous abortion;steatosis;stomach irritation/si [Side Effect];systematic review;teratogenicity/si [Side Effect];thrombocytopenia/si [Side Effect];tremor;triacylglycerol lipase blood level;urinalysis;urine volume;virus hepatitis;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];4 phenylbutyric acid/dt [Drug Therapy];4 phenylbutyric acid/pd [Pharmacology];alpha tocopherol/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;curcumin/dt [Drug Therapy];curcumin/pd [Pharmacology];dimercaprol/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];pyridoxine;tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics];Wilson disease protein/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/pd [Pharmacology];zinc sulfate/dt [Drug Therapy],"Ferenci, P.;Czlonkowska, A.;Stremmel, W.;Houwen, R.;Rosenberg, W.;Schilsky, M.;Jansen, P.;Moradpour, D.;Gitlin, J.",2012,01 Mar,http://dx.doi.org/10.1016/j.jhep.2011.11.007,0,0,
1190,Canine models for copper homeostasis disorders,"Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted. Copyright © 2016 by the authors; licensee MDPI, Basel, Switzerland.",atp7a;atp7b;Bedlington terrier;commd1;Copper toxicosis;Genetics;Labrador retriever;Menkes disease;Nutrition;Wilson disease;animal model;autoimmune disease;canine model;chelation therapy;copper homeostasis;copper metabolism;gene mapping;gene mutation;homeostasis;human;hypersensitivity;liver cirrhosis;liver transplantation;Menkes syndrome;nausea;neurologic disease;nonhuman;protein expression;proteinuria;review;single nucleotide polymorphism;trans Golgi network;copper;copper zinc superoxide dismutase;glutathione;Menkes protein;metallothionein;penicillamine;trientine;Wilson disease protein;zinc derivative,"Wu, X.;Leegwater, P. A. J.;Fieten, H.",2016,04 Feb,http://dx.doi.org/10.3390/ijms17020196,0,0,
1191,D-penicillamine combined with inhibitors of hydroperoxide metabolism enhances lung and breast cancer cell responses to radiation and carboplatin via H<inf>2</inf>O<inf>2</inf>-mediated oxidative stress,"D-penicillamine (DPEN), a copper chelator, has been used in the treatment of Wilson's disease, cystinuria, and rheumatoid arthritis. Recent evidence suggests that DPEN in combination with biologically relevant copper (Cu) concentrations generates H<inf>2</inf>O<inf>2</inf> in cancer cell cultures, but the effects of this on cancer cell responses to ionizing radiation and chemotherapy are unknown. Increased steady-state levels of H<inf>2</inf>O<inf>2</inf> were detected in MB231 breast and H1299 lung cancer cells following treatment with DPEN (100 micro M) and copper sulfate (15 micro M). Clonogenic survival demonstrated that DPEN-induced cancer cell toxicity was dependent on Cu and was significantly enhanced by depletion of glutathione [using buthionine sulfoximine (BSO)] as well as inhibition of thioredoxin reductase [using Auranofin (Au)] prior to exposure. Treatment with catalase inhibited DPEN toxicity confirming H<inf>2</inf>O<inf>2</inf> as the toxic species. Furthermore, pretreating cancer cells with iron sucrose enhanced DPEN toxicity while treating with deferoxamine, an Fe chelator that inhibits redox cycling, inhibited DPEN toxicity. Importantly, DPEN also demonstrated selective toxicity in human breast and lung cancer cells, relative to normal untransformed human lung or mammary epithelial cells and enhanced cancer cell killing when combined with ionizing radiation or carboplatin. Consistent with the selective cancer cell toxicity, normal untransformed human lung epithelial cells had significantly lower labile iron pools than lung cancer cells. These results support the hypothesis that DPEN mediates selective cancer cell killing as well as radio-chemo-sensitization by a mechanism involving metal ion catalyzed H<inf>2</inf>O<inf>2</inf>-mediated oxidative stress and suggest that DPEN could be repurposed as an adjuvant in conventional cancer therapy. Copyright © 2017 Elsevier Inc.",Breast cancer;D-penicillamine;Hydrogen peroxide;Lung cancer;Oxidative metabolism;Transition metal ions;aerobic metabolism;animal experiment;animal model;article;breast epithelium cell;cancer cell;cancer chemotherapy;controlled study;cytotoxicity;female;h1299 cancer cell line;human;human cell;ionizing radiation;limit of quantitation;lung cancer cell line;MDA MB 231 cell line;mouse;nonhuman;oxidative stress;priority journal;rate constant;steady state;tumor growth;tumor volume;tumor xenograft;buthionine sulfoximine/ec [Endogenous Compound];carboplatin/pd [Pharmacology];catalase/ec [Endogenous Compound];copper sulfate;glutathione/ec [Endogenous Compound];hydroperoxide/cb [Drug Combination];hydroperoxide/pd [Pharmacology];penicillamine/cb [Drug Combination];penicillamine/pd [Pharmacology];thioredoxin reductase/ec [Endogenous Compound],"Sciegienka, S. J.;Solst, S. R.;Falls, K. C.;Schoenfeld, J. D.;Klinger, A. R.;Ross, N. L.;Rodman, S. N.;Spitz, D. R.;Fath, M. A.",2017,01 Jul,http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.001,0,0,
1192,Pseudo-dominant inheritance in Wilson's disease,,Carrier;Consecutive generation;Neuroimaging;Wilson's disease;adult;ataxia;case report;ceruloplasmin blood level;copper metabolism;depression/th [Therapy];disease duration;dominant inheritance;dysarthria;female;gait disorder;gene mutation;genetic analysis;hepatitis;heterozygote;human;insomnia;letter;liver cirrhosis;mesencephalon;middle aged;neurologic examination;nuclear magnetic resonance imaging;positron emission tomography;psychotherapy;putamen;red nucleus;slurred speech;splenomegaly;trace metal blood level;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];fluorodeoxyglucose;liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Park, H.;Park, D. K.;Kim, M. S.;Yoon, J. H.",2016,01 Jan,http://dx.doi.org/10.1007/s10072-015-2394-8,0,0,
1193,A new risk locus in the ZEB2 gene for schizophrenia in the Han Chinese population,"The ZEB2 gene encodes the Zinc Finger E-box binding protein. As a key regulator of epithelial mesenchymal differentiation, ZEB2 plays an important role in the pathogenesis of cancer, and its high level expression has been observed in glioma patients. Different mutations in this gene have been identified in patients with Mowat-Wilson syndrome. A previous genome-wide association study (GWAS) of schizophrenia conducted in Caucasians has shown a significant association of rs12991836, located near the ZEB2 gene, with schizophrenia. Thus, we conducted a case control study to further investigate whether this genomic region is also a susceptibility locus for schizophrenia in the Han Chinese population. In total, 1248 schizophrenia (SCZ) cases (mean age+/-S.D., 36.44+/-9.0years), 1344 bipolar disorder (BPD) cases (mean age+/-S.D., 34.84+/-11.44years), 1056 major depressive disorder (MDD) cases (mean age+/-S.D., 34.41+/-12.09years) and 1248 healthy control samples (mean age+/-S.D., 30.62+/-11.35years) were recruited. We genotyped 12 SNPs using the Sequenom MassARRAY platform in this study. We found that rs6755392 showed a significant association with SCZ (rs6755392: adjusted P<inf>allele</inf>=0.016; adjusted P<inf>genotype</inf>=0.052; OR (95% CI)=1.201 (1.073~1.344)). Additionally, two haplotypes (TCTG, TCTA) were also significantly associated with SCZ. This is the first study claiming the association of the genetic risks of rs6755392 in the ZEB2 gene with schizophrenia. Copyright © 2015 Elsevier Inc.",Bipolar disorder;Case-control study;Han Chinese;Major depressive disorder;Schizophrenia;zeb2;adult;article;case control study;Chinese;controlled study;female;gene;gene linkage disequilibrium;gene locus;genetic risk;genetic susceptibility;genetic variability;genotype;human;major clinical study;male;schizophrenia/et [Etiology];single nucleotide polymorphism;ZEB2 gene,"Khan, R. A. W.;Chen, J.;Wang, M.;Li, Z.;Shen, J.;Wen, Z.;Song, Z.;Li, W.;Xu, Y.;Wang, L.;Shi, Y.",2016,April 03,http://dx.doi.org/10.1016/j.pnpbp.2015.12.001,0,0,
1194,"Gene therapy of Wilson disease: A ""golden"" opportunity using rAAV on the 50th anniversary of the discovery of the virus",,acute liver failure;adaptive immunity;Adeno associated virus;alanine aminotransferase blood level;cell division;cell specificity;cellular immunity;ex vivo gene transfer;ex vivo study;gene expression;gene targeting;gene therapy;gene transfer;hemophilia B;Herpes simplex virus;human;human chromosome;immunogenicity;immunosuppressive treatment;inverted terminal repeat;liver failure;liver injury;liver transplantation;mental disease;nonhuman;open reading frame;phenotype;priority journal;protein expression;proto oncogene;review;species difference;Wilson disease;adenovirus vector;alanine aminotransferase/ec [Endogenous Compound];blood clotting factor 9;capsid protein;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];double stranded DNA;lentivirus vector;penicillamine/po [Oral Drug Administration];prednisolone;single stranded DNA;trientine/po [Oral Drug Administration];Wilson disease protein/ec [Endogenous Compound];zinc/po [Oral Drug Administration],"Roy-Chowdhury, J.;Schilsky, M. L.",2016,01 Feb,http://dx.doi.org/10.1016/j.jhep.2015.11.017,0,0,
1195,Essentially deadly: Living with toxic elements: Humans and plants have evolved various mechanisms to deal with and even adopt toxic heavy metals,"Organisms have evolved to deal with or make use of toxic metals. Understanding these mechanisms could help to protect the health of mine workers, tackle malnourishment, or improve ways to clean up polluted environments. Copyright © 2015 The Author.",article;blood sampling;Helianthus annuus;human;mass spectrometry;medical research;miner;nonhuman;osmotic stress;phytomining;phytoremediation;plant evolution;priority journal;sister chromatid exchange;smoking;sorghum;Sorghum bicolour;structural chromosome aberration;telomere;varietas;water availability;Wilson disease;aluminum;arsenic;cadmium;chromium;cobalt;copper;heavy metal;lead;manganese;nickel;selenium;toxic substance;zinc,"Hunter, P.",2015,01 Dec,http://dx.doi.org/10.15252/embr.201541601,0,0,
1196,A case report on Wilson's disease-induced liver cirrhosis,"Wilson's disease (WD) is an inherited autosomal genetic abnormality which results in impairment in cellular copper transport. Overtime, this may lead to liver cirrhosis. The main focus of this case is to shows the importance of taking a medical history. Here, we discuss a case of a 35-year-old male diagnosed with WD-induced liver cirrhosis and portal hypertension. He was physically very weak. Since the same genetic abnormality was the reason for the death of his sibling which was not considered while taking the medical history of this patient, this led to a late diagnosis of 4 years while the patient's condition became worst. Herein, we report a case that provides an insight to medical professionals about taking proper medical history of patients Copyright © 2017 The Authors.",Copper deposit;Liver cirrhosis;Wilson's disease;abdominal distension;adult;article;bacterial peritonitis;case report;Child Pugh score;disease association;dysphagia;end stage liver disease score 23;headache;health status;human;limb weakness;liver cirrhosis/co [Complication];liver cirrhosis/di [Diagnosis];liver graft rejection/co [Complication];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver transplantation;male;medical history;pain;portal hypertension;protein blood level;rating scale;seizure;tertiary health care;treatment response;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ascazin/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;everolimus/dt [Drug Therapy];liver protective agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];rifagut/dt [Drug Therapy];t azoran/dt [Drug Therapy];udiliv/dt [Drug Therapy];unclassified drug,"Vincent, B.;James, A.;Syamaprasad, T. V.;Reji, R.;Reghu, R.",2017,April,http://dx.doi.org/10.22159/ajpcr.2017.v10i4.16329,0,0,
1197,Clinical features and outcome in patients with osseomuscular type of Wilson's disease,"Background: Wilson 's disease with osseomuscular type is a rare condition, which often lacks typical hepatic and neurological symptoms and causes misdiagnoses easily. During the past 10 years, eight Chinese patients of osseomuscular type of Wilson's disease were identified in our clinic. Methods: Clinical information was gathered from medical records and follow-ups. The genetic testing was performed in each patient. Serum ceruloplasmin, Kayser-Fleischer rings, liver function, brain magnetic resonance imaging and abdominal ultrasonography were also evaluated. Results: The median age of onset is 12 years of age. The patients had their initial musculoskeletal conditions with arthralgia or joint deformity, while the hepatic or neurologic signs were minimal. Most patients (6/8) eventually developed clinical neurological symptoms afterwards with a median interval of 36 months. All of them had normal liver function and low serum ceruloplasmin (<0.1 g/L). Most patients (6/8) present with Kayser-Fleischer rings and abnormal hepatic ultrasonography. The arthralgia was resolved with copper chelation therapy. Conclusions: Wilson's disease with osseomuscular type occurs without typical hepatic or neurological symptoms, which makes the clinical diagnosis challenging. Serum ceruloplasmin, abdominal ultrasonography, ophthalmic examination and genetic testing help to establish the diagnosis. Early diagnosis can initiate an effective treatment and prevent the further damage. Copyright © 2017 The Author(s).",Arthralgia;atp7b;Copper;Deformity;Osteoarthritis;abdominal radiography;adolescent;arthralgia/dt [Drug Therapy];article;bone malformation;ceruloplasmin blood level;chelation therapy;child;clinical article;clinical feature;clinical outcome;clubfoot;cornea disease;dysarthria;echography;eye examination;female;follow up;genetic screening;human;kayser fleischer ring;liver function;male;medical record;musculoskeletal function;neuroimaging;nuclear magnetic resonance imaging;preschool child;psychomotor disorder;school child;tremor;valgus knee;varus knee;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/cb [Drug Combination];copper/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];succimer/cb [Drug Combination];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];unithiol/cb [Drug Combination];unithiol/dt [Drug Therapy];unithiol/iv [Intravenous Drug Administration],"Yu, H.;Xie, J. J.;Chen, Y. C.;Dong, Q. Y.;Dong, Y.;Ni, W.;Wu, Z. Y.",2017,17 Feb,http://dx.doi.org/10.1186/s12883-017-0818-1,0,0,
1198,Wilson disease: A most unusual patient,,adult;article;case report;ceruloplasmin blood level;copper blood level;epistaxis;family history;female;gene mutation;glucosuria;hemolysis;hepatomegaly;human;human tissue;liver biopsy;liver cell;patient referral;priority journal;splenectomy;splenomegaly/su [Surgery];urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;copper 64;glutamine;histidine;penicillamine/dt [Drug Therapy],"Walshe, J. M.",2016,01 Feb,http://dx.doi.org/10.1093/qjmed/hcv142,0,0,
1199,Dysregulation of brain metal homeostasis in bilirubin-induced neurologic dysfunction,,basal ganglion;binding affinity;blood brain barrier;brain region;chelation therapy;comorbidity;concentration (parameters);globus pallidus;hemolysis;hippocampus;homeostasis;human;letter;neurologic disease;newborn period;nonhuman;priority journal;retina cell;subthalamic nucleus;Wilson disease;bilirubin;chaperone;copper;hydroxyl radical;iron;metal ion;penicillamine;zinc,"Lakatos, L.;Balla, G.",2016,01 Jul,http://dx.doi.org/10.1016/j.jtemb.2016.03.004,0,0,
1200,Advances in understanding and treating liver diseases during pregnancy: A review,"Liver disease in pregnancy is rare but pregnancyrelated liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients. Copyright © 2015 Baishideng Publishing Group Inc. All rights reserved. © 2015 The Author(s).",Acute fatty liver of pregnancy;Haemolysis elevated liver enzymes;Hyperemesis gravidarum;Intrahepatic cholestasis of pregnancy;Liver injury;Low platelets;Pregnancy;article;autoimmune liver disease/dt [Drug Therapy];autoimmune liver disease/et [Etiology];blood pressure regulation;Budd Chiari syndrome/et [Etiology];clinical feature;disease course;early diagnosis;eclampsia/et [Etiology];fatty liver/et [Etiology];fatty liver/th [Therapy];female;fetus monitoring;follow up;gallstone;HELLP syndrome/et [Etiology];human;hyperemesis gravidarum/et [Etiology];hyperemesis gravidarum/th [Therapy];hypertension/et [Etiology];intrahepatic cholestasis/dt [Drug Therapy];intrahepatic cholestasis/et [Etiology];liver disease/et [Etiology];liver transplantation;liver tumor/et [Etiology];metabolic disorder/et [Etiology];parenteral nutrition;plasmapheresis;preeclampsia/et [Etiology];pregnancy disorder/et [Etiology];primary biliary cirrhosis/et [Etiology];primary sclerosing cholangitis/et [Etiology];virus hepatitis/et [Etiology];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];immunosuppressive agent/dt [Drug Therapy];infusion fluid;penicillamine/dt [Drug Therapy];steroid/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy],"Kamimura, K.;Abe, H.;Kawai, H.;Kamimura, H.;Kobayashi, Y.;Nomoto, M.;Aoyagi, Y.;Terai, S.",2015,07 May,http://dx.doi.org/10.3748/wjg.v21.i17.5183,0,0,
1201,"Prospective evaluation of the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample","Hepatic copper determination is an important test for the diagnosis of Wilson's disease (WD). However, the method has not been standardized, the diagnostic accuracy has not been evaluated prospectively, and the optimal cut-off value remains controversial. Accordingly, we aimed to prospectively evaluate the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample. Patients for whom a liver biopsy was indicated were consecutively enrolled. Hepatic copper content was determined with atomic absorption spectroscopy. All assays were performed using careful quality control by a single technician. WD diagnosis was based on WD score or its combination with clinical follow-up results. A total of 3,350 consecutive patients underwent liver biopsy. Six hundred ninety-one patients, including 178 with WD, underwent two passes of liver biopsy with hepatic copper determination. Mean hepatic content in WD patients was 770.6+/-393.2 mug/g dry weight (wt). Sensitivity, specificity, and positive and negative predictive values of hepatic copper content for WD diagnosis in the absence of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis at the cut-off value of 250 mug/g dry wt. were 94.4%, 96.8%, 91.8%, and 97.8%, respectively. The most useful cut-off value was 209 mug/g dry wt, with a sensitivity and specificity of 99.4% and 96.1%, respectively. A total of 23.3% of patients without WD and PBC had hepatic copper content >75 mug/g dry wt. Conclusion: A liver biopsy sample of more than 1 mg dry wt may reliably reflect hepatic copper content and should be used for hepatic copper determination. Hepatic copper determination is a very valid procedure for the diagnosis of WD, and the most useful cut-off value is 209 mug/g dry wt. Copyright © 2015 by the American Association for the Study of Liver Diseases.",accuracy;adolescent;adult;alanine aminotransferase blood level;alcohol liver disease;alkaline phosphatase blood level;alpha 1 antitrypsin deficiency;article;aspartate aminotransferase blood level;atomic absorption spectrometry;Budd Chiari syndrome;ceruloplasmin blood level;child;conservative treatment;diagnostic accuracy;Dubin Johnson syndrome;evaluation study;family history;female;follow up;genetic screening;Gilbert disease;hemochromatosis;hepatic copper content;heterozygote;human;human tissue;hypotension;infant;jaundice;liver biopsy;liver fibrosis;liver function test;liver histology;major clinical study;male;neurologic disease;newborn;nonalcoholic fatty liver;pneumothorax/co [Complication];polymyositis;portal hypertension;predictive value;primary biliary cirrhosis;primary sclerosing cholangitis;priority journal;prospective study;sensitivity and specificity;toxic hepatitis;treatment duration;virus hepatitis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy];zinc,"Yang, X.;Tang, X. P.;Zhang, Y. H.;Luo, K. Z.;Jiang, Y. F.;Luo, H. Yu;Lei, J. H.;Wang, W. Long;Li, M. M.;Chen, H. C.;Deng, S. L.;Lai, L. Y.;Liang, J.;Zhang, M.;Tian, Y.;Xu, Y.",2015,01 Dec,http://dx.doi.org/10.1002/hep.27932,0,0,
1202,<sup>1</sup>H NMR-based metabolomics investigation of copper-laden rat: A model of Wilson's disease,"Background and Purpose: Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established. Materials and Methods: A combination of <sup>1</sup>HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment. Results: Copper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha-ketoglutarate (alpha-KG), dimethylamine, N-acetylglutamate (NAG), N-acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, alpha-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database) is introduced to identify the metabolic pathway influenced by the copper-laden diet. Conclusion: The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular mechanism underlying disorder due to WD. Copyright © 2015 Xu et al.",amino acid blood level;animal experiment;animal model;article;bioaccumulation;blood sampling;controlled study;copper metabolism;glucose blood level;male;metabolomics;molecular pathology;nonhuman;proton nuclear magnetic resonance;rat;urinalysis;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];2 oxoglutaric acid/ec [Endogenous Compound];4 hydroxyphenylacetic acid/ec [Endogenous Compound];alanine/ec [Endogenous Compound];copper;creatinine/ec [Endogenous Compound];dimethylamine/ec [Endogenous Compound];formic acid/ec [Endogenous Compound];glucose/ec [Endogenous Compound];glycoprotein/ec [Endogenous Compound];hippuric acid/ec [Endogenous Compound];lactic acid/ec [Endogenous Compound];leucine/ec [Endogenous Compound];n acetylglutamic acid/ec [Endogenous Compound];n acetylglycoprotein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];taurine/ec [Endogenous Compound];unclassified drug;valine/ec [Endogenous Compound],"Xu, J.;Jiang, H.;Li, J.;Cheng, K. K.;Dong, J.;Chen, Z.",2015,07 Apr,http://dx.doi.org/10.1371/journal.pone.0119654,0,0,
1203,Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines,"AIM: To study the effect of anti-copper treatment for survival of hepatic cells expressing different ATP7B mutations in cell culture. METHODS: The most common Wilson disease (WD) mutations p.H1069Q, p.R778L and p.C271*, found in the ATP7B gene encoding a liver copper transporter, were studied. The mutations represent major genotypes of the United States and Europe, China, and India, respectively. A human hepatoma cell line previously established to carry a knockout of ATP7B was used to stably express WD mutants. mRNA and protein expression of mutant ATP7B , survival of cells, apoptosis, and protein trafficking were determined. RESULTS: Low temperature increased ATP7B protein expression in several mutants. Intracellular ATP7B localization was significantly impaired in the mutants. Mutants were classified as high, moderate, and no survival based on their viability on exposure to toxic copper. Survival of mutant p.H1069Q and to a lesser extent p.C271* improved by D-penicillamine (DPA) treatment, while mutant p.R778L showed a pronounced response to zinc (Zn) treatment. Overall, DPA treatment resulted in higher cell survival as compared to Zn treatment; however, only combined Zn + DPA treatment fully restored cell viability. CONCLUSION: The data indicate that the basic impact of a genotype might be characterized by analysis of mutant hepatic cell lines. Copyright © 2016 Baishideng Publishing Group Inc. All rights reserved.",Atp7b;D-penicillamine;Mutations;Therapy;Wilson disease;Zinc;apoptosis;article;ATP7B gene;cell survival;cell viability;controlled study;drug mechanism;gene expression;gene mutation;hepatoma cell;human;human cell;ic50;in vitro study;protein expression;protein localization;protein transport;treatment response;penicillamine/pd [Pharmacology];Wilson disease protein/ec [Endogenous Compound];zinc/pd [Pharmacology],"Chandhok, G.;Horvath, J.;Aggarwal, A.;Bhatt, M.;Zibert, A.;Schmidt, H. H. J.",2016,28 Apr,http://dx.doi.org/10.3748/wjg.v22.i16.4109,0,0,
1204,"Penicillamine induced pseudopseudoxanthoma elasticum in a patient with wilson's disease, which role plays the hepatologist?",,Adverse effect;D-penicillamin;Pseudoxanthoma elasticum;Toxicity;Wilson's disease;adult;case report;drug substitution;drug withdrawal;echocardiography;eye examination;eye fundus;female;human;letter;liver cirrhosis;papule;portal hypertension;pseudoxanthoma elasticum/di [Diagnosis];pseudoxanthoma elasticum/dt [Drug Therapy];pseudoxanthoma elasticum/si [Side Effect];skin biopsy;skin fragility;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration],"Ibanez-Samaniego, L.;Ochoa-Palominos, A.;Catalina-Rodriguez, M. V.;Salcedo-Plaza, M.;Clemente-Ricote, G.",2015,05 Aug,,0,0,
1205,Management for acute liver failure of Wilson disease: Indication for liver transplantation,,acute liver failure/di [Diagnosis];acute liver failure/su [Surgery];blood transfusion;clinical feature;editorial;human;liver transplantation;pathophysiology;plasma exchange;treatment indication;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];copper chelator/cb [Drug Combination];copper chelator/dt [Drug Therapy];unclassified drug;zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Harada, M.",2017,01 Mar,http://dx.doi.org/10.1111/hepr.12717,0,0,
1206,Plasma exchange and chelator therapy rescues acute liver failure in Wilson disease without liver transplantation,"Aim: Wilson disease (WD) in patients with a New Wilson Index (NWI) score >= 11 is fatal, and these patients are good candidates for liver transplantation (LT). However, plasma exchange and chelator therapy are indispensable and effective even for WD with a score >= 11. Moreover, continuous hemodiafiltration (CHDF) with these treatments is essential for acute liver failure (ALF) in WD with hepatic encephalopathy because CHDF can exclude toxic metabolites that may cause damage to the brain. Here, we describe four rescued patients presenting with ALF in WD and discuss the available treatment options. Methods: We have experienced 11 male and 8 female patients presenting with WD at the Department of Pediatrics, Kumamoto University Hospital between 1999 and 2014. A male and 4 female patients were diagnosed as WD with ALF using a combination of clinical findings and biochemical tests. Results: The NWI score was >= 11 in cases 1 to 3. Cases 1 and 2 with hepatic encephalopathy received plasma exchange, CHDF, coagulation factor replacement treatment (CFRT) and LT. Cases 3 and 4 without encephalopathy obtained stable status without LT by plasma exchange, blood infusion, and CFRT. Conclusions: It is better to undergo LT for WD patients with a NWI score >= 11, however, there is a possibility of remission by plasma exchange and medical therapy even without LT. WD patients with a NWI score >= 11can be rescued by conservative therapy when the ALF of WD does not present with ALF and hepatic encephalopathy. Therefore, ALF with hepatic encephalopathy itself is an indication for LT in WD. Copyright © 2016 The Japan Society of Hepatology",Continuous hemodiafiltration;New Wilson Index;prothrombin time;abdominal distension;abdominal pain;acute liver failure/co [Complication];acute liver failure/dt [Drug Therapy];acute liver failure/su [Surgery];acute liver failure/th [Therapy];adolescent;adult;agranulocytosis/co [Complication];article;ascites/co [Complication];blood transfusion;case report;ceruloplasmin blood level;chelation therapy;child;diet therapy;echography;fatigue;female;fever/co [Complication];hemoglobin blood level;hemolytic anemia/di [Diagnosis];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/su [Surgery];hepatic encephalopathy/th [Therapy];human;hyperbilirubinemia/di [Diagnosis];jaundice/co [Complication];jaundice/di [Diagnosis];liver function;liver transplantation;loss of appetite;malaise;male;New Wilson Index Score;pancytopenia;partial thromboplastin time;plasma exchange;preschool child;pulsatile drug release;remission;scoring system;substitution therapy;treatment indication;treatment outcome;treatment planning;treatment response;urinary excretion;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];x-ray computed tomography;blood clotting factor/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cyclosporin/dt [Drug Therapy];fresh frozen plasma;granulocyte colony stimulating factor;hemoglobin/ec [Endogenous Compound];interferon/dt [Drug Therapy];penicillamine/dt [Drug Therapy];steroid/dt [Drug Therapy];trientine/dt [Drug Therapy],"Kido, J.;Matsumoto, S.;Momosaki, K.;Sakamoto, R.;Mitsubuchi, H.;Inomata, Y.;Endo, F.;Nakamura, K.",2017,01 Mar,http://dx.doi.org/10.1111/hepr.12711,0,0,
1207,Two cases of D-penicillamine-induced elastosis perforans serpiginosa,,adult;case report;corticosteroid therapy;elastosis/di [Diagnosis];elastosis/dt [Drug Therapy];elastosis/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];histopathology;human;human tissue;hyperpigmentation;letter;male;papule;skin atrophy;skin biopsy;Wilson disease/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];corticosteroid/tp [Topical Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tazarotene/dt [Drug Therapy];tazarotene/tp [Topical Drug Administration],"Liang, J.;Wang, D.;Xu, J.;Chen, L.",2016,July-August,http://dx.doi.org/10.4103/0378-6323.178907,0,0,
1208,Delay in Diagnosis of Wilson Disease in Children With Insidious Psychiatric Symptoms: A Case Report and Review of the Literature,,adolescent;aggression;alcoholism;antibiotic therapy;anxiety disorder/dt [Drug Therapy];article;automutilation;basal ganglion;behavior disorder;case report;ceruloplasmin blood level;delayed diagnosis;demyelinating disease;depression/dt [Drug Therapy];dysarthria;dysphagia;encephalitis;epistaxis;human;hypersalivation;knee pain;male;mental disease;mental instability;mood disorder/dt [Drug Therapy];neurologic disease;nuclear magnetic resonance imaging;osmosis;pons;predictive value;streptococcal pharyngitis/dt [Drug Therapy];suicide;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];antibiotic agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];escitalopram/dt [Drug Therapy];gluconate zinc/dt [Drug Therapy];trientine/dt [Drug Therapy],"Millard, H.;Zimbrean, P.;Martin, A.",2015,01 Nov,http://dx.doi.org/10.1016/j.psym.2015.07.008,0,0,
1209,Structure and synaptic function of metal binding to the amyloid precursor protein and its proteolytic fragments,"Alzheimer's disease (AD) is ultimately linked to the amyloid precursor protein (APP). However, current research reveals an important synaptic function of APP and APP-like proteins (APLP1 and 2). In this context various neurotrophic and neuroprotective functions have been reported for the APP proteolytic fragments sAPPalpha, sAPPbeta and the monomeric amyloid-beta peptide (Abeta). APP is a metalloprotein and binds copper and zinc ions. Synaptic activity correlates with a release of these ions into the synaptic cleft and dysregulation of their homeostasis is linked to different neurodegenerative diseases. Metal binding to APP or its fragments affects its structure and its proteolytic cleavage and therefore its physiological function at the synapse. Here, we summarize the current data supporting this hypothesis and provide a model of how these different mechanisms might be intertwined with each other. Copyright © 2017 Wild, August, Pietrzik and Kins.",Alzheimer's disease;Amyloid precursor protein (APP);Copper;Synaptic transmission;Zinc;Alzheimer disease;amyloid plaque;article;blood brain barrier;brain dysfunction;brain function;cell adhesion;cerebellum;cerebrospinal fluid;conformational transition;cytotoxicity;dimerization;hippocampus;human;Menkes syndrome;metal binding;microenvironment;neurotransmission;nonhuman;nuclear magnetic resonance;oligomerization;oxidative stress;postsynaptic density;protein degradation;protein expression;protein phosphorylation;synapse vesicle;synaptic potential;trans Golgi network;Wilson disease;4 aminobutyric acid A receptor/ec [Endogenous Compound];ADAM10 endopeptidase/ec [Endogenous Compound];alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid/ec [Endogenous Compound];amyloid beta protein/ec [Endogenous Compound];amyloid precursor protein/ec [Endogenous Compound];amyloid protein/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];clioquinol;copper ion;dopamine beta monooxygenase/ec [Endogenous Compound];membrane protein/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];metalloprotein/ec [Endogenous Compound];monophenol monooxygenase/ec [Endogenous Compound];n methyl dextro aspartic acid receptor/ec [Endogenous Compound];neurotrophic factor/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc/ec [Endogenous Compound];zinc binding protein/ec [Endogenous Compound];zinc ion;zinc transporter/ec [Endogenous Compound],"Wild, K.;August, A.;Pietrzik, C. U.;Kins, S.",2017,31 Jan,http://dx.doi.org/10.3389/fnmol.2017.00021,0,0,
1210,Multifocal myoclonus as a heralding manifestation of Wilson disease,"Wilson disease (WD) is one of the few curable movement disorders that manifests with varied presentations so that WD needs to be considered in any patient with a movement disorder under the age of 50 years. Although WD is one of the causes of myoclonus, it is rarely seen in WD and usually as an associated finding. We report a case of an adolescent female patient of WD who presented with cortical multifocal myoclonus of 6-month duration with later development of generalized dystonia, extrapyramidal syndrome, and cognitive decline. Kayser-Fleischer ring was present on slit lamp examination. Serum copper, urine copper, serum ceruloplasmin, and magnetic resonance imaging brain were consistent with the diagnosis of WD. Copper chelation was started along with other symptomatic treatments and diet modifications. Myoclonus had resolved by 3-month follow-up with the improvement of other symptoms. This case report emphasizes that myoclonus can be the main and presenting feature of WD. Copyright © 2017 Journal of Pediatric Neurosciences Published by Wolters Kluwer - Medknow.",Dystonia;epilepsy;myoclonus;Wilson disease;abnormal posture;ADL disability;article;attention disturbance;case report;child;clinical feature;cognitive defect;dietary intake;disease duration;dysarthria;dysphagia;eye disease;fall risk;feeding difficulty;female;human;hypersalivation;kayser fleischer ring;muscle examination;muscle rigidity;myoclonus/dt [Drug Therapy];school child;shuffling gait;slit lamp microscopy;task performance;walking difficulty;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];clonazepam/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Verma, R.;Holla, V.;Pandey, S.;Rizvi, I.",2016,October-December,http://dx.doi.org/10.4103/1817-1745.199468,0,0,
1211,"Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics","Objective: To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. Materials and methods: Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. Results: Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 +/- 14.5 years), still at a young mean age (27.5 +/- 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. Conclusion: RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered. Copyright © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",frequency;restless legs syndrome;restless legs syndrome mimics;Willis-Ekbom disease;Wilson's disease;adolescent;adult;age;alcohol consumption;article;Beck Depression Inventory;Child Pugh score;chorea;clinical article;clinical feature;cohort analysis;comorbidity;confounding variable;controlled study;creatinine blood level;daytime somnolence;depression/dt [Drug Therapy];differential diagnosis;disease assessment;disease course;disease duration;disease severity;dystonia;Epworth sleepiness scale;family history;female;ferritin blood level;folic acid blood level;Global Assessment Scale for Wilson Disease;human;international restless legs syndrome study group rating scale;iron blood level;iron metabolism;kidney function;laboratory test;liver function;male;morbidity;neurologic examination;night;Pittsburgh Sleep Quality Index;polyneuropathy;polysomnography;pregnancy;restless legs syndrome/di [Diagnosis];sex;sleep disorder assessment;sleep quality;structured interview;tremor/dt [Drug Therapy];Unified Wilson Disease Rating Scale;Wilson disease/dt [Drug Therapy];antidepressant agent/dt [Drug Therapy];benzodiazepine derivative;creatinine/ec [Endogenous Compound];cyanocobalamin/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];folic acid/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];levodopa/dt [Drug Therapy];levodopa/ec [Endogenous Compound];neuroleptic agent;nicotine;penicillamine/dt [Drug Therapy];potassium/ec [Endogenous Compound];psychotropic agent;transferrin/ec [Endogenous Compound];trientine/dt [Drug Therapy];urea/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy],"Trindade, M. C.;Bittencourt, T.;Lorenzi-Filho, G.;Alves, R. C.;de Andrade, D. C.;Fonoff, E. T.;Bor-Seng-Shu, E.;Machado, A. A.;Teixeira, M. J.;Barbosa, E. R.;Tribl, G. G.",2017,01 Feb,http://dx.doi.org/10.1111/ane.12585,0,0,
1212,Trace metal regulation of neuronal apoptosis: From genes to behavior,"The genetically programmed form of neuronal death known as apoptosis plays a role in many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease. Apoptosis is also responsible for neuronal death after traumatic brain and spinal cord injury, stroke, and seizures. The cognitive and behavioral consequences of all of these disorders can be devastating. Unfortunately the mechanisms that regulate neuronal apoptosis are complex. However, it is this very complexity that provides us with a wide array of potential targets for the development of anti-apoptotic strategies. Thus, our lab is currently exploring the molecular and cellular mechanisms responsible for neuronal apoptosis, with a particular focus on the role of the metals copper, zinc, and iron. Each of these metals is essential for normal central nervous system (CNS) development and function. However, imbalances, either excess or deficiency, can result in neuronal apoptosis. In this review, we show the relationship between these metals in neurodegenerative disorders and CNS injury, and the mechanisms that govern neuronal survival and apoptosis. © 2005 Elsevier Inc. All rights reserved.",Anorexia;Copper;Iron;Motor behavior;Parkinson's disease;Trauma;Wilson's disease;Zinc;Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis;apoptosis;behavior;central nervous system function;clinical trial;cognition;degenerative disease/et [Etiology];DNA damage;drug absorption;gene mutation;genetic damage;human;Huntington chorea/et [Etiology];iron overload;iron restriction;nerve cell necrosis;nervous system development;nonhuman;Parkinson disease/et [Etiology];Parkinson disease/th [Therapy];priority journal;regulatory mechanism;review;Wilson disease/et [Etiology];zinc deficiency/dt [Drug Therapy];zinc deficiency/ep [Epidemiology];copper/to [Drug Toxicity];deferoxamine/pd [Pharmacology];iron/to [Drug Toxicity];iron chelate/pd [Pharmacology];trace metal/to [Drug Toxicity];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity];zinc/ip [Intraperitoneal Drug Administration];zinc/iv [Intravenous Drug Administration];zinc/po [Oral Drug Administration];zinc/pa [Parenteral Drug Administration];zinc/pk [Pharmacokinetics];zinc/pd [Pharmacology],"Levenson, C. W.",2005,15 Oct,http://dx.doi.org/10.1016/j.physbeh.2005.08.010,0,0,
1213,Coexisting Parkinson's and Wilson's Disease: Chance or Connection?,,atp7b;Wilson's disease;Young onset Parkinson's disease;aged;bradykinesia;brain depth stimulation;case report;copper blood level;drug withdrawal;dyskinesia;dystonia;female;follow up;gastric ulcer bleeding/si [Side Effect];gene mutation;globus pallidus;heterozygosity;human;latent period;letter;liver biopsy;neuroimaging;nuclear magnetic resonance imaging;Parkinson disease/dt [Drug Therapy];positron emission tomography;priority journal;rigidity;slit lamp microscopy;somatosensory evoked potential;Spaniard;treatment duration;treatment response;tremor;Unified Parkinson Disease Rating Scale;urinary excretion;Wilson disease/dt [Drug Therapy];6 fluorodopa f 18;carbidopa plus levodopa/ae [Adverse Drug Reaction];carbidopa plus levodopa/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];leucine rich repeat kinase 2/ec [Endogenous Compound];levodopa/dt [Drug Therapy];parkin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pergolide/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Gasca-Salas, C.;Alonso, A.;Gonzalez-Redondo, R.;Obeso, J. A.",2017,01 Mar,http://dx.doi.org/10.1017/cjn.2016.327,0,0,
1214,Kayser-Fleisher Ring and Sunflower Cataract in a Child with Wilson's Disease,,abdominal distension;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;bilirubin blood level;blood clotting time;case report;cataract;child;clinical examination;clinical feature;cornea disease;eye examination;female;human;international normalized ratio;jaundice;Kayser Fleisher ring;lethargy;liver biopsy;school child;sunflower cataract;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Koay, C. L.;Zahari, M.;Lee, W. S.",2017,01 Feb,http://dx.doi.org/10.1016/j.pedneo.2016.03.011,0,0,
1215,Neuropsychiatric Presentation of Wilson Disease in an Adolescent Male,,academic failure;adolescent;aggression;case report;ceruloplasmin blood level;clinical feature;compensated liver cirrhosis;copper blood level;depression/dt [Drug Therapy];diet restriction;diplopia;drug dose increase;dysarthria;emotional disorder;esophagus varices;gaze;gene;homicide;human;impulsiveness;leukopenia;male;mood change;note;nuclear magnetic resonance imaging;portal hypertension;priority journal;skin bruising;splenomegaly;suicidal ideation;thrombocytopenia;tongue disease;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aripiprazole/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];escitalopram/dt [Drug Therapy];gluconate zinc/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Schindler, E. A. D.;Guo, X. M.;Schrag, M.;Ghoshal, S.;Schilsky, M. L.;Beslow, L. A.",2016,01 Oct,http://dx.doi.org/10.1055/s-0036-1586225,0,0,
1216,Utility of transient elastography to predict the outcome of Decopper Therapy in a 13 year-old girl with acute on chronic liver failure from Wilson disease,"Background: Wilson disease (WD) is a rare autosomal recessive disorder characterized by abnormal copper accumulation. Decopper is the effective treatment with an excellent outcome if the disease is early diagnosed [1]. However, the majority of patients with severe manifestation as acute liver failure or acute on chronic liver failure need urgent liver transplantation [2]. Though, recent study showed that ultrasound-based transient elastography (Fibroscan) could be used to predict liver fibrosis with the cut-off value of 6.6 kPa [3], there has been no clinical useful data of Fibroscan in untreated WD especially to predict the outcome of the initial treatment. Methods: Result: A 13-year-old girl with 6 months of jaundice, ascites and coagulopathy, was referred from a local hospital for liver transplantation. At our hospital, Wilson disease was diagnosed with positive KF rings, low serum ceruloplasmin, high urine copper level and neuropsychiatric involvement. Liver biopsy was omitted due to uncorrectable coagulopathy. Transient elastography was measured with the value of 50.6 kPa (Pic.1A). During admission, patients had encephalopathy grade I-II with fluctuation of consciousness and hyperreflexia. Treatment was started with depenicillamine and zinc sulfate. Four weeks later, clinical features and laboratory parameters were still abnormal (Table 1), however, Fibroscan value was dramatically decreased (17.8 kPa) (Pic.1B) reflects the good treatment response and patient compliance. Conclusion: We present a case of WD with severe manifestation that might need liver transplantation. Liver transplantation is less possible with unpredictable time of waiting list, consequently, decopper therapy is started after WD diagnosis. The treatment response will take time up to 3 months of the initiation [1], consequently, the novel parameter to predict the outcome of treatment is necessary. We do recommend using transient elastography, apart from clinical response and liver function test, not only to predict the treatment outcome but also to evaluate the patient compliance in the long term follow-up. (Table Presented).",acute on chronic liver failure;adolescent;ascites;blood clotting disorder;case report;ceruloplasmin blood level;child;clinical feature;consciousness;controlled study;diagnosis;female;follow up;girl;hospital admission;human;human tissue;hyperreflexia;jaundice;liver biopsy;liver fibrosis;liver function test;liver transplantation;transient elastography;treatment response;ultrasound;urine;Wilson disease;endogenous compound;zinc sulfate,"Sintusek, P.;Piriyakitphiboon, V.;Atjimakul, T.;Chongsrisawat, V.",2017,February,http://dx.doi.org/10.1007/s12072-016-9783-9,0,0,
1217,Copper homeostasis as a therapeutic target in amyotrophic lateral sclerosis with SOD1 mutations,"Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease affecting both upper and lower motor neurons, and currently, there is no cure or effective treatment. Mutations in a gene encoding a ubiquitous antioxidant enzyme, Cu,Zn-superoxide dismutase (SOD1), have been first identified as a cause of familial forms of ALS. It is widely accepted that mutant SOD1 proteins cause the disease through a gain in toxicity but not through a loss of its physiological function. SOD1 is a major copper-binding protein and regulates copper homeostasis in the cell; therefore, a toxicity of mutant SOD1 could arise from the disruption of copper homeostasis. In this review, we will briefly review recent studies implying roles of copper homeostasis in the pathogenesis of SOD1-ALS and highlight the therapeutic interventions focusing on pharmacological as well as genetic regulations of copper homeostasis to modify the pathological process in SOD1-ALS. Copyright © 2016 by the authors; licensee MDPI, Basel, Switzerland.","Amyotrophic lateral sclerosis;Copper homeostasis;Cu, Zn-superoxide dismutase;autosomal recessive disorder;binding affinity;disease course;drug targeting;gene expression regulation;gene mutation;homeostasis;human;nerve degeneration;nonhuman;pathogenesis;protein expression;protein synthesis regulation;review;signal transduction;upregulation;Wilson disease/dt [Drug Therapy];copper zinc superoxide dismutase/ec [Endogenous Compound];glucocorticoid receptor;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid;trientine/dt [Drug Therapy]","Tokuda, E.;Furukawa, Y.",2016,May,http://dx.doi.org/10.3390/ijms17050636,0,0,
1218,Coexistence of Wilson's disease and sarcoidosis in a 35-yearold female,"Background: The simultaneous diagnosis of two relatively rare coexisting diseases. Patients and methods: Description of clinical and laboratory findings. Results: A thirty-five year-old female was referred to a neurology department for symptoms of resting, postural and kinetic tremor of the upper extremities as well as head tremor. Diagnostic workup revealed Kaiser-Fleischer rings in both eyes, high levels of copper in the urine (200 mug/24 h with normal value [n.v.] <100, low levels of ceruloplasmine (17.5 mg/dL-n.v.22-58) and marginally low serum copper (0.6 mug/m.L-n.v.0.7-1.4). A diagnosis of Wilson's disease was established. The patient's chest radiograph, however, showed enlarged pulmonary hili which were confirmed, by computed tomography, to represent enlarged lymph nodes. The patient's angiotensin converting enzyme was 72.2 U/L (n.v. 12-68), spirometry was normal (FEV1: 87%, FVC: 88%, Dlco: 81%, FRC: 89%, RV: 82%, TLC: 84%) and she did not have considerable hemoglobin desaturation during a six-minute walk test (97% to 96%, distance walked: 360 m). A bronchoalveolar lavage was performed: Cells: 0.132x10<sup>6</sup>, alveolar macrophages 44%, lymphocytes 42%, neutrophils 6%, mononuclear 3%, eosinophils 5%. Ratio CD4/CD8: 2.57. The patient was started on triethylenetetramine (Trientin) for her primary disease and was followed up for her stage I sarcoidosis. Three years later she remains clinically stable with no respiratory symptoms, with unchanged findings from spirometry and computed tomography regarding sarcoidosis. The coexistence of these two diseases is rare. Only one similar case has been reported. It concerned a forty-three year-old male, who presented with symptoms and signs of cirrhosis and no neurologic symptoms. He had been diagnosed with sarcoidosis nine years earlier and been treated with corticosteroids. Conclusions: The existence of one rare disease should not deter the search towards a coexisting disease if signs and symptoms are not compatible with the first one.",adult;case report;computer assisted tomography;copper blood level;diagnosis;eosinophil;female;forced expiratory volume;forced vital capacity;gene expression;head twitch;human;human tissue;liver cirrhosis;lung alveolus macrophage;lung diffusion capacity;lung lavage;lymph node hyperplasia;lymphocyte;male;neurologic disease;neurology;neutrophil;normal value;rare disease;sarcoidosis;six minute walk test;spirometry;thorax radiography;tremor;upper limb;urine;Wilson disease;CD4 antigen;CD8 antigen;ceruloplasmin;corticosteroid;dipeptidyl carboxypeptidase;endogenous compound;hemoglobin;trientine,"Markopoulou, A.;Aggelis, N.;Vlahopoulos, D.;Peglidou, V.;Kalliolou, E.;Arnaoutoglou, M.;Kalaitzidou, E.",2012,,http://dx.doi.org/10.3978/j.issn.2072-1439.2012.s069,0,0,
1219,Elastosis perforans serpiginosa in a patient with Wilson's disease,,adult;atrophy/si [Side Effect];biopsy;case report;diagnostic error;Down syndrome;drug withdrawal;Ehlers Danlos syndrome;elastosis;elastosis perforans serpiginosa;histology;human;human tissue;inflammation;male;note;priority journal;pruritus;rash/si [Side Effect];scar formation/si [Side Effect];tinea corporis;Wilson disease;alkaline phosphatase/ec [Endogenous Compound];antifungal agent;penicillamine/ae [Adverse Drug Reaction];protein lysine 6 oxidase/ec [Endogenous Compound];pyridoxine,"Thwaites, P. A.;Khan, S. A.;Asadi, K.;Angus, P. W.",2017,01 Feb,http://dx.doi.org/10.1016/S2468-1253%2816%2930212-6,0,0,
1220,Update on the clinical management of Wilson's disease,"Wilson's disease (WD), albeit relatively rare, is an important genetic metabolic disease because of highly effective therapies that can be lifesaving. It is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Neurologic, psychiatric and hepatologic problems in WD are very nonspecific, and we discuss the most common clinical phenotypes. The diagnosis remains laboratory based, and here we review the most important challenges and pitfalls in laboratory evaluation of WD, including the emerging role of genetic testing in WD diagnosis. WD is a monogenic disorder but has very high allelic heterogeneity with >500 disease-causing mutations identified, and new insights into phenotype-genotype correlations are also reviewed. The gold standard of therapy is chelation of excessive copper, but many unmet needs exist because of possible clinical deterioration in treated patients and potential adverse effects associated with currently available chelating medications. We also review the most promising novel therapeutic approaches, including chelators targeting specific cell types, cell transplantation and gene therapy. Copyright © 2017 Hedera.",atp7b;Chelation;Copper;Gene therapy;Wilson's disease;cell therapy;clinical evaluation;clinical feature;disease association;dystonia;genetic association;genetic screening;gold standard;human;limited mobility;liver disease;liver transplantation;neuroimaging;outcome assessment;review;treatment indication;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];tetrathiomolybdate ammonium/dt [Drug Therapy];zinc/dt [Drug Therapy],"Hedera, P.",2017,13 Jan,http://dx.doi.org/10.2147/TACG.S79121,0,0,
1221,Surgical treatment in patients with Wilson's disease,"Background: Wilson's disease is an autosomal recessive disorder due to mutation in ATB 7B gene, which is a membrane-bound copper-transporting ATPase. The impaired excretion of copper results in an increase in serum levels and accumulation of copper in the body. Various signs can be observed in liver, nervous system, kidneys, eyes, heart. There are also changes in blood chemistry. Objective: A forty-six-year-old female patient presents with Wilson's disease in the treatment rooms at the Faculty of Dentistry in Plovdiv. She needs complete dental care. She has also had an ischaemic stroke. Methods and results: As the treatment plan started with extraction of teeth under local anaesthesia, a complete blood count and INR test were performed. Oral mucosa and bone were obtained by biopsy for evidence of pigments in these tissues. The biopsy results showed accumulation of copper in them as well. Conclusion: It's a rare disorder, approximately 1 in 40 000, severely affecting the liver and nervous system. It requires in-depth analysis and discussion over the clinical and paraclinical approach with a view to avoid possible complications and achieve the desired results. Copyright © 2017, Medical University - Varna. All rights reserved.",Hemorrhagic stroke;inr;Kayser-Fleischer ring;Morbus Wilson;adult;article;ataxic gait;bleeding;blood cell count;brain ischemia;case report;computer assisted tomography;copper metabolism;dental procedure;dysarthria;female;follow up;gastroscopy;hospitalization;human;human tissue;limb weakness;liver biopsy;middle aged;nuclear magnetic resonance imaging;oral biopsy;panoramic radiography;periodontitis;prothrombin time;treatment planning;tremor;walking difficulty;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];amylase/ec [Endogenous Compound];ascorbic acid;bilirubin/ec [Endogenous Compound];C reactive protein/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];glucose/ec [Endogenous Compound];immunoglobulin A/ec [Endogenous Compound];immunoglobulin G/ec [Endogenous Compound];immunoglobulin M/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];potassium;sodium;uric acid/ec [Endogenous Compound],"Cholakova, R.;Drangov, M.;Markova, K.;Zidarova, V.;Avramova, M.",2017,01 Jan,http://dx.doi.org/10.5272/jimab.2017231.1447,0,0,
1222,Metallomics and new targets in metal-based drug discovery,,Alzheimer disease;angiogenesis;antiangiogenic activity;cancer chemotherapy;cell division;colon carcinoma;drug design;drug selectivity;extracellular matrix;gene targeting;human;metallomics;nerve degeneration;nonhuman;note;phase 2 clinical trial(topic);protein phosphorylation;signal transduction;Wilson disease;cisplatin;clioquinol;copper;disulfiram;metal;microRNA/ec [Endogenous Compound];mitogen activated protein kinase 1/ec [Endogenous Compound];mitogen activated protein kinase 3/ec [Endogenous Compound];peroxiredoxin 3/ec [Endogenous Compound];protein kinase B/ec [Endogenous Compound];ruthenium complex;tetrathiomolybdic acid;vasculotropin/ec [Endogenous Compound];vasculotropin receptor 2/ec [Endogenous Compound],"La Mendola, D.;Rizzarelli, E.",2016,01 Dec,,0,0,
1223,Edema and Cirrhosis Caused by Wilson's Disease,,article;case report;ceruloplasmin blood level;chelation therapy;child;computer assisted tomography;human;hypertransaminasemia;hypoalbuminemia;leg edema;liver cirrhosis;male;pancytopenia/dt [Drug Therapy];provocation test;school child;scrotal swelling;slit lamp;symptomatology;weight gain;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Huang, J. Y.;Shih, H. H.",2015,01 Dec,http://dx.doi.org/10.1016/j.pedneo.2015.03.009,0,0,
1224,Liver transplantation in severe neurological forms of Wilson disease; the French experience,"Introduction: The standard treatment of Wilson disease (WD) is chelating copper agent or zinc salts. Liver transplantation (LT) is indicated in cases of acute liver failure or advanced cirrhosis. The indication of LT in neurological forms without liver decompensation remains controversial. The aim of this study is to evaluate the effect of LT in WD with severe neurological symptoms without decompensated liver function. Methods. This is a retrospective study. From 2002 to 2015, nine patients (mean age 21 [12-42] years) underwent a LT in France for severe neurological complications without neurological improvement despite medical treatment, without acute liver failure. All patients received chelating copper and 2 patients received chelating copper with zinc salts. Results. Neurological symptoms were heterogeneous, combining dystonic postures, akinesia, cerebellar ataxia, chorea and parkinsonian syndrome. The CHILD score was A for all patients at the time of transplantation. All patients had cirrhosis after analysis of the native liver. Mean interval between diagnosis of WD and LT was 11.4 [5-28] months and the mean follow-up time after transplant was 50 [2-42] months. Five patients (mean age 19 [12- 30] years) with a mean follow-up of 80 [2-156] months had a neurological improvement after LT, with a significant gain on the quality of life. Four patients (mean age 24 [15-42] years) had no significant improvement of neurological symptoms and died of infectious complications, after a mean interval of 13 [2-36] months. Three of the four deceased patients had severe parkinsonian syndrome and akinesia limiting movements and deglutition. No correlation between genetic mutations and the prognosis has been demonstrated. Conclusion: Liver transplantation is an effective treatment option in WD for patients with worsening neurological symptoms despite medical treatment, even in the absence of liver failure. Patients with unfavorable evolution died of severe sepsis. A long history of fixed neurological symptoms could be a pejorative factor.",acute liver failure;adolescent;adult;akinesia;body posture;cerebellar ataxia;chelation;child;chorea;clinical article;clinical trial;diagnosis;drug therapy;dystonia;follow up;France;gene mutation;human;human tissue;infectious complication;liver cirrhosis;liver function;liver transplantation;neurological complication;parkinsonism;prognosis;quality of life;retrospective study;sepsis;swallowing;Wilson disease;zinc derivative,"Sobesky, R.;Poujois, A.;Vanlemmens, C.;Hermeziu, B.;Adam, R.;Cherqui, D.;Castaing, D.;Samuel, D.;Woimant, F.;Duclos-Vallee, J. C.",2016,May,http://dx.doi.org/10.1097/01.tp.0000483259.57907.d4,0,0,
1225,Cutaneous Lymphangiectasia in Systemic Sclerosis,,acanthosis;adult;case report;cystinuria;differential diagnosis;endothelial progenitor cell;female;finger ulcer;human;hydrostatic pressure;keloid;localized scleroderma;lymph vessel;lymphangiectasis;medical history;middle aged;note;priority journal;rash;Raynaud phenomenon;skin biopsy;skin infection;systemic sclerosis;telangiectasia;verruca vulgaris;Wilson disease;endothelial cell antibody/ec [Endogenous Compound];penicillamine,"Hoa, S.;Leclair, V.;Hudson, M.",2017,01 Feb,http://dx.doi.org/10.1002/art.40000,0,0,
1226,Evaluation of renal function in children with wilson's disease. [Turkish],"Introduction: In this study it was aimed to evaluate the renal functions in Wilson's disease (WD) using urinary N-acetyl-beta-D-glucosaminidase (NAG) and NAG/ creatinine activity index. Materials and Methods: Twenty children of similar age and gender with WD were determined to be the patient group and 37 healthy children were determined to be the control group for the study. NAG levels were calculated as mlU/L and NAG activity index was determined as mlU/mg. Results: While four (20%) patients were asymptomatic at diagnosis, chronic hepatitis, neurologic WD, fulminant hepatitis, and acute hepatitis were observed in six (30%), five (25%), three (15%), and two (10%) patients, respectively. Of children, 13 (65%) were on trientine and zinc treatment and seven (35%) were on d-penicillamine and zinc. Ten (50%) children had proteinuria, one (5%) had glycosuria, and one (5%) had microscopic hematuria. While mean urine sodium and creatinine levels were significantly lower compared to controls (p=0.048 and p=0.001, respectively), NAG and NAG index were significantly higher (p=0.049 and p=0.03). Clinical presentation was observed to be not effective on those parameters (p>0.05). No relationship was found between Child-Pugh score and these parameters (p>0.05). Conclusions: It was concluded that while WD itself and/or the drugs that are used for the treatment have negative effects on renal functions for children with WD, however it does not have any effect on the liver damage severity and clinical presentation of the disease. Copyright © Telif Hakki 2017 Galenos Yayinevi Guncel Pediatri Dergisi, Galenos Yayinevi tarafindan yayinlanmistir.",Children;N-acetyl-beta-D-glucosaminidase;Renal function;Wilson's disease;acute hepatitis;article;child;chronic hepatitis;clinical article;controlled study;disease severity;glucosuria;hematuria;human;kidney function;normal human;proteinuria;sodium urine level;Wilson disease/dt [Drug Therapy];creatinine/ec [Endogenous Compound];n acetyl beta glucosaminidase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Tabel, Y.;Selimoglu, M. A.;Varol, F. I.;Elmas, A. T.;Gungor, S.;Karabiber, H.",2017,April,http://dx.doi.org/10.4274/jcp.43760,0,0,
1227,Discoveries of conventional synthetic disease modifying anti-rheumatic drugs - Serendipity or flawless reasoning?,"Most of the conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) for treating rheumatoid arthritis (RA) were discovered serendipitously. Of course, discoveries do require serendipity, but it is not simply a random process or chance event. It is a process in which an unexpected event is seized upon by a creative mind that chooses to pay attention to the event, and unravels its mystery followed by its careful application for the benefit of mankind. Rheumatology is replete with such brilliant minds helping patients to come out from a hopeless illness and move towards a quality life that is almost as good as normal. In this short review, historical perspective of some of the older and current csDMARDs-related discoveries is described. Copyright © 2015 Indian Rheumatology Association. All rights reserved.",Anti-malarials;Gold salts;Leflunomide;Methotrexate;Sulfasalazine;antiinflammatory activity;antiproliferative activity;blood toxicity/si [Side Effect];CD4+ T lymphocyte;drug approval;drug development;drug efficacy;drug indication;drug mechanism;drug safety;drug tolerability;history of medicine;human;immunomodulation;liver toxicity/si [Side Effect];low drug dose;malaria/dt [Drug Therapy];nephrotoxicity/si [Side Effect];nonhuman;phase 2 clinical trial(topic);priority journal;randomized controlled trial(topic);retina disease/si [Side Effect];review;rheumatoid arthritis/dt [Drug Therapy];skin discoloration/si [Side Effect];skin lupus erythematosus/dt [Drug Therapy];systemic lupus erythematosus/dt [Drug Therapy];tuberculosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];aminopterin/pd [Pharmacology];antimalarial agent/dt [Drug Therapy];chloroquine/ae [Adverse Drug Reaction];chloroquine/dt [Drug Therapy];conventional synthetic disease modifying antirheumatic drug/ct [Clinical Trial];conventional synthetic disease modifying antirheumatic drug/dv [Drug Development];conventional synthetic disease modifying antirheumatic drug/dt [Drug Therapy];conventional synthetic disease modifying antirheumatic drug/pd [Pharmacology];cortisone/pd [Pharmacology];cyclophosphamide/pd [Pharmacology];disease modifying antirheumatic drug/ct [Clinical Trial];disease modifying antirheumatic drug/dv [Drug Development];disease modifying antirheumatic drug/dt [Drug Therapy];disease modifying antirheumatic drug/pd [Pharmacology];gold salt/dt [Drug Therapy];hydroxychloroquine/ae [Adverse Drug Reaction];hydroxychloroquine/dt [Drug Therapy];hydroxychloroquine/pd [Pharmacology];indometacin/pd [Pharmacology];leflunomide/ct [Clinical Trial];leflunomide/dt [Drug Therapy];leflunomide/pd [Pharmacology];mepacrine/ae [Adverse Drug Reaction];mepacrine/dt [Drug Therapy];methotrexate/ae [Adverse Drug Reaction];methotrexate/ct [Clinical Trial];methotrexate/dt [Drug Therapy];methotrexate/im [Intramuscular Drug Administration];methotrexate/pd [Pharmacology];nonsteroid antiinflammatory agent/pd [Pharmacology];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];phenylbutazone/pd [Pharmacology];quinine/dt [Drug Therapy];salazosulfapyridine/dt [Drug Therapy];salazosulfapyridine/pd [Pharmacology];teriflunomide/pd [Pharmacology];unclassified drug,"Malaviya, A. N.",2016,,http://dx.doi.org/10.1016/j.injr.2015.12.004,0,0,
1228,A heartbreaking case of Wilson's disease: Takotsubo cardiomyopathy complicating fulminant hepatic failure,,adolescent;anemia/di [Diagnosis];case report;Coombs test;diarrhea/dt [Drug Therapy];echography;electrocardiogram;epigastric pain;eye jaundice/di [Diagnosis];female;fulminant hepatic failure/co [Complication];fulminant hepatic failure/di [Diagnosis];fulminant hepatic failure/su [Surgery];fulminant hepatic failure/th [Therapy];hepatic encephalopathy/th [Therapy];human;hypothyroidism/dt [Drug Therapy];jaundice;laboratory test;letter;liver transplantation;lymphadenopathy/di [Diagnosis];medical history;nausea and vomiting;physical examination;plasmapheresis;priority journal;respiratory tract intubation;ST segment depression;ST segment elevation;systolic heart murmur/di [Diagnosis];takotsubo cardiomyopathy/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];X-ray computed tomography;alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];antidiarrheal agent/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];levothyroxine/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Adar, T.;Chen, S.;Mizrahi, M.",2014,01 Nov,http://dx.doi.org/10.1111/tri.12350,0,0,
1229,A special case of recurrent gross hematuria: Answers,"Wilson's disease (WD) is an autosomal recessive disorder, and has a variety of presentations. We reported a case of 9-year-old girl who presented with a history of recurrent gross hematuria, renal histological changes of IgA nephropathy, and finally had been confirmed to be Wilson's disease-associated IgA nephropathy. Copyright © 2015, IPNA.",ATP7B gene;Child;Gross hematuria;IgA nephropathy;Wilson's disease;article;case report;disease association;erythrocyte;female;hematuria;human;hyperplasia;immunoglobulin A nephropathy;immunoperoxidase staining;interstitium;kidney biopsy;kidney tubule epithelium;priority journal;school child;urinalysis;Wilson disease;immunoglobulin A/ec [Endogenous Compound];zinc sulfate/po [Oral Drug Administration],"Tu, J.;Chen, C.;Li, H.;Chu, M.;Geng, H.",2017,01 Feb,http://dx.doi.org/10.1007/s00467-015-3265-5,0,0,
1230,Wilson's disease patient with iron metabolism discharge barriers: A case report,"Wilson's disease (WD) is an autosomal genetic disease. In the present study, the patient was a 35-year-old woman who exhibited drinking bucking (bulbar paralysis) and dysphagia for a period of nine years. Genetic analysis of the patient identified the Thr935Met and Pro992Leu mutations, which lead to copper metabolism discharge barriers. Moreover, magnetic resonance imaging revealed a susceptibility-weighted imaging (SWI) hyperintense area in the bilateral substantia nigra and lenticular nuclei. These SWI observations indicated that 'mineral deposits' were present. The present case demonstrates that the SWI hyperintense area in the bilateral lenticular nuclei, substantia nigra and red nucleus combined with the patient's symptoms indicated that there is a possibility to diagnose WD when it is not detected by genetic analysis. In addition, it demonstrates that systemic mineral removal treatment (including manganese, iron and copper) may be successful for the initial treatment of WD. Copyright © 2016 Spandidos Publications. All rights reserved.",Compound heterozygous mutation;Iron metabolism;Susceptibility-weighted imaging;Wilson's disease;adult;article;bulbar paralysis;case report;dysarthria;dysphagia;dystonia;female;gait disorder/dt [Drug Therapy];gene mutation;genetic analysis;human;iron transport;leukocyte count;neutrophil;nuclear magnetic resonance imaging;proteinuria;schizophrenia;substantia nigra;susceptibility weighted imaging;thrombocyte count;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];benserazide plus levodopa/dt [Drug Therapy];ceruloplasmin;fibrinogen/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc/dt [Drug Therapy],"Cai, G.;Huang, X.;Ye, Q.;Xiong, W.;Duan, Q.",2017,01 Jan,http://dx.doi.org/10.3892/etm.2016.3928,0,0,
1231,Clinical spectrum of eye malformations in four patients with Mowat-Wilson syndrome,"Mowat-Wilson syndrome (MWS) is a rare genetic syndrome characterized by a specific facial gestalt, intellectual deficiency, Hirschsprung disease and multiple congenital anomalies. Heterozygous mutations or deletions in the zinc finger E-box-binding homeobox2 gene (ZEB2) cause MWS. ZEB2 encodes for Smad-interacting protein 1, a transcriptional co-repressor involved in TGF-beta and BMP pathways and is strongly expressed in early stages of development in mice. Eye abnormalities have rarely been described in patients with this syndrome. Herein, we describe four patients (two males and two females; mean age 7 years) with MWS and eye malformations. Ocular anomalies included, iris/retinal colobomas, atrophy or absence of the optic nerve, hyphema, and deep refraction troubles, sometimes with severe visual consequences. All eye malformations were asymmetric and often unilateral and all eye segments were affected, similarly to the nine MWS cases with ophthalmological malformations previously reported (iris/chorioretinal/optic disc coloboma, optic nerve atrophy, retinal epithelium atrophy, cataract, and korectopia). In human embryo, ZEB2 is expressed in lens and neural retina. Using the present report and data from the literature, we set out to determine whether or not the presence of eye manifestations could be due to specific type or location of mutations. We concluded that the presence of eye malformations, although a rare feature in MWS, should be considered as a part of the clinical spectrum of the condition. Copyright © 2015 Wiley Periodicals, Inc.",Eye malformation;Mowat-Wilson;Syndromic Hirschsprung disease;zeb2;adult;article;blindness/di [Diagnosis];cataract/di [Diagnosis];child;clinical feature;clonic seizure;coloboma/di [Diagnosis];congenital malformation/cn [Congenital Disorder];congenital malformation/et [Etiology];echocardiography;electroencephalography;embryo;eye examination;eye malformation/di [Diagnosis];face dysmorphia/di [Diagnosis];female;fetus echography;gene;gene mutation;Hirschsprung disease/di [Diagnosis];Hirschsprung disease/su [Surgery];human;human tissue;hyphema/di [Diagnosis];ileostomy;iris coloboma/di [Diagnosis];korectopia/di [Diagnosis];male;medical history;microphthalmia/di [Diagnosis];mowat wilson syndrome/cn [Congenital Disorder];mowat wilson syndrome/et [Etiology];nuclear magnetic resonance imaging;optic nerve atrophy/di [Diagnosis];optic nerve hypoplasia/di [Diagnosis];physical examination;prenatal diagnosis;preschool child;priority journal;psychomotor retardation;rectum biopsy;retinal coloboma/di [Diagnosis];retinal epithelium atrophy/di [Diagnosis];school child;sequence analysis;tonic clonic seizure/di [Diagnosis];young adult;ZEB2 gene,"Bourchany, A.;Giurgea, I.;Thevenon, J.;Goldenberg, A.;Morin, G.;Bremond-Gignac, D.;Paillot, C.;Lafontaine, P. O.;Thouvenin, D.;Massy, J.;Duncombe, A.;Thauvin-Robinet, C.;Masurel-Paulet, A.;El Chehadeh, S.;Huet, F.;Bron, A.;Creuzot-Garcher, C.;Lyonnet, S.;Olivier-Faivre, L.",2015,01 Jul,http://dx.doi.org/10.1002/ajmg.a.36898,0,0,
1232,The spectrum of ZEB2 mutations causing the Mowat-Wilson syndrome in Japanese populations,"Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by moderate or severe intellectual disability, a characteristic facial appearance, microcephaly, epilepsy, agenesis or hypoplasia of the corpus callosum, congenital heart defects, Hirschsprung disease, and urogenital/renal anomalies. It is caused by de novo heterozygous loss of function mutations including nonsense mutations, frameshift mutations, and deletions in ZEB2 at 2q22. ZEB2 encodes the zinc finger E-box binding homeobox 2 protein consisting of 1,214 amino acids. Herein, we report 13 nonsense and 27 frameshift mutations from 40 newly identified MWS patients in Japan. Although the clinical findings of all the Japanese MWS patients with nonsense and frameshift mutations were quite similar to the previous review reports of MWS caused by nonsense mutations, frameshift mutations and deletions of ZEB2, the frequencies of microcephaly, Hirschsprung disease, and urogenital/renal anomalies were small. Patients harbored mutations spanning the region between the amino acids 55 and 1,204 in wild-type ZEB2. There was no obvious genotype-phenotype correlation among the patients. A transfection study demonstrated that the cellular level of the longest form of the mutant ZEB2 protein harboring the p.D1204Rfs*29 mutation was remarkably low. The results showed that the 3'-end frameshift mutation of ZEB2 causes MWS due to ZEB2 instability. © 2014 Wiley Periodicals, Inc.",Frameshift mutation;Mowat-Wilson syndrome;Nonsense mutation;zeb2;adolescent;adult;article;carboxy terminal sequence;child;clinical article;congenital malformation/et [Etiology];female;gene deletion;gene frequency;genetic association;genetic transfection;genomic instability;genotype phenotype correlation;Hirschsprung disease;human;Japanese (people);kidney malformation;male;microcephaly;molecular pathology;mowat wilson syndrome/et [Etiology];mutational analysis;mutator gene;preschool child;priority journal;school child;urogenital tract malformation;wild type;young adult;ZEB2 gene;amino acid/ec [Endogenous Compound];mutant protein/ec [Endogenous Compound];unclassified drug;ZEB2 protein/ec [Endogenous Compound],"Yamada, Y.;Nomura, N.;Yamada, K.;Matsuo, M.;Suzuki, Y.;Sameshima, K.;Kimura, R.;Yamamoto, Y.;Fukushi, D.;Fukuhara, Y.;Ishihara, N.;Nishi, E.;Imataka, G.;Suzumura, H.;Hamano, S. I.;Shimizu, K.;Iwakoshi, M.;Ohama, K.;Ohta, A.;Wakamoto, H.;Kajita, M.;Miura, K.;Yokochi, K.;Kosaki, K.;Kuroda, T.;Kosaki, R.;Hiraki, Y.;Saito, K.;Mizuno, S.;Kurosawa, K.;Okamoto, N.;Wakamatsu, N.",2014,August,http://dx.doi.org/10.1002/ajmg.a.36551,0,0,
1233,Hemolytic anemia as the first clinical presentation of Wilson disease: A pediatric case. [Spanish],"Wilson disease is an autosomal recessive disorder of the coppers hepatic metabolism; it results in toxicity due to accumulation of the mineral. The hemolytic anemia is present in 17% at some point of the disease, although it is a rare initial clinical presentation. Case report: 11 years old boy who presented with negative Coombs hemolytic anemia and elevation of liver enzymes. The possibility of Wilson disease was considered, which was confirmed with the finding of a Kayser-Fleischer ring in the eye exam. He also had a low ceruloplasmin level in plasma and a high urinary copper excretion. He was treated with D-penicillamine and pyridoxine.",Coombs Test;Hemolytic Anemia;Wilson Disease;article;case report;ceruloplasmin blood level;child;human;hypertransaminasemia;male;school child;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Henao, J. A.;Valverde, K.;Avila, M. L.",2016,December,http://dx.doi.org/10.5546/aap.2016.e436,0,0,
1234,Treatment of Neurodegenerative Diseases by Chelators,"Changes in metal ion homeostasis occur with aging which may precipitate the development of neurodegenerative diseases in susceptible individuals. Slight increases in iron content of specific brain regions, sometimes as little as two-fold, may have a devastating effect on brain function. In this current review we shall initially discuss changes that occur in brain iron homeostasis during healthy aging and longevity, and how alterations of its concentration and distribution may expedite various neurodegenerative diseases. Changes in metal ion homeostasis of other metal ions, namely copper and zinc, also occur in neurodegenerative diseases and will be discussed. Over the past five years the use of iron chelators to slow the progression of the disease and even improve clinical symptoms in some neurodegenerative diseases has been reported; clinical trials have confirmed their efficacy in specific neurodegenerative diseases, namely Friederich's ataxia and Parkinson's disease. The development of new chelators which are able to target specific regions of the brain, combined with drugs which are able to modulate the inflammatory processes, will further advance hope for the eradication of these debilitating neurodegenerative diseases. Copyright © The Royal Society of Chemistry 2017.",aceruloplasminaemia;age related macular degeneration;aging;Alzheimer disease;autosomal recessive disorder;blood brain barrier;brain hemorrhage;degenerative disease/dt [Drug Therapy];Friedreich ataxia;homeostasis;human;Huntington chorea;inflammation;iron metabolism;multiple sclerosis;neurodegeneration with brain iron accumulation;neuroferritinopathy;neuroimaging;nuclear magnetic resonance imaging;Parkinson disease;Wilson disease;zinc homeostasis;chelating agent/dt [Drug Therapy];copper;iron;metal ion,"Ward, R. J.;Dexter, D. T.;Crichton, R. R.",2017,,http://dx.doi.org/10.1039/9781782623892-00153,0,0,
1235,Biological consequences of zinc deficiency in the pathomechanisms of selected diseases,"From many points of view, zinc is one of the most important trace elements in biological systems. Many articles describe the well-known role of this metal in human physiology and pathophysiology, but in the related literature, there is a lack of current and reliable reviews of the role of zinc deficiency in many diseases. In this article, we describe the role of zinc deficiency in the oxidative stress control, immune response, proliferation, and pathogenesis and pathophysiology of selected diseases such as depression, cardiovascular diseases, diabetes mellitus, Alzheimer's disease, and Wilson's disease. Copyright © 2014 The Author(s).",Zinc deficiency;Zinc diseases;Zinc pathomechanisms;Alzheimer disease;biology;cardiovascular disease;diabetes mellitus;diseases;human;immune response;oxidative stress;pathogenesis;pathophysiology;physiology;Wilson disease;metal;trace element;zinc,"Jurowski, K.;Szewczyk, B.;Nowak, G.;Piekoszewski, W.",2014,19 Apr,http://dx.doi.org/10.1007/s00775-014-1139-0,0,0,
1236,Manifestations and Evolution of Wilson Disease in Pediatric Patients Carrying the Very Rare atb7b Mutation l708p. [],"OBJECTIVES: To characterize a group of 11 pediatric patients, aged from 3 to 13 years old, affected by Wilson's disease in the island of Gran Canaria. METHODS: Genetic, biochemical and pathological features, together with their response to treatment and clinical evolution have been analyzed for this group of patients. RESULTS: Genetically, the group was rather homogeneous, with a very high prevalence of the L708P mutation (four homozygotes and five heterozygotes). Despite being initially screened due to asymptomatic hyper-transaminemia, all patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is highly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content were found to be of great diagnostic value, while urine copper measurements were found to be much less conclusive. All patients responded well to treatment with D-penicillamine with no documented adverse reactions. CONCLUSIONS: The patients in Gran Canaria constitute, overall, one of the largest groups of WD patients with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.",patient;human;mutation;Wilson disease;heterozygote;liver injury;copper blood level;blood level;diagnostic value;allele;adverse drug reaction;mutant;prevalence;homozygote;urine;copper;ceruloplasmin;penicillamine;polypeptide;protein,"Pena-Quintana, L.;Garcia-Luzardo, M. R.;Garcia-Villarreal, L.;Arias-Santos, M. D.;Garay-Sanchez, P.;Santana, A.;Gonzalez-Santana, D.;Ramos-Varela, J. C.;Rial-Gonzalez, R.;Tugores, A.",2011,,http://dx.doi.org/10.1097/MPG.0b013e318230130c,0,0,
1237,Pyoderma Gangrenosum-A New Manifestation of Wilson Disease?,"Seventeen year old girl, a known case of Wilson disease presented to us with a non-healing skin ulcer followed by appearance of jaundice, ascites and progressive fatigue of 1 month duration. She was diagnosed to have Wilson disease 5 years back and had been well controlled on d-penicillamine. On enquiry, she was found to be noncompliant with her medication in the preceding 6 months. On examination, she had severe pallor, icterus with moderate ascites and oedema feet. Investigations revealed severe haemolytic anemia and deranged liver function. The lesion was diagnosed to be pyoderma gangrenosum on skin biopsy. The appearance of a cutaneous lesion followed by deterioration in the liver disease and hemolysis suggested uncontrolled Wilson disease as the triggering factor. Chelation therapy improved her haemoglobin and liver function as well as led to healing of the ulcer. We describe pyoderma gangrenosum as a new manifestation of Wilson disease. Copyright © 2015 INASL.",D-penicillamine;Extra hepatic;Liver;Skin;adolescent;antibody titer;article;ascites;bleeding;case report;chelation therapy;colonoscopy;Coombs test;debridement;disease association;disease duration;erythrocyte transfusion;eye jaundice;fatigue;female;foot edema;hemolysis;hemolytic anemia/di [Diagnosis];human;inflammatory bowel disease/di [Diagnosis];jaundice;liver disease;liver function;lymphocytic infiltration;neutrophil chemotaxis;occult blood test;pallor;palpation;patient compliance;priority journal;protein diet;pustule;pyoderma gangrenosum/co [Complication];pyoderma gangrenosum/di [Diagnosis];pyoderma gangrenosum/dt [Drug Therapy];skin biopsy;skin defect;skin ulcer/di [Diagnosis];sodium restriction;spleen size;tachycardia;ulcer healing;weakness;Wilson disease/dt [Drug Therapy];antinuclear antibody/ec [Endogenous Compound];fusidic acid/dl [Intradermal Drug Administration];hemoglobin/ec [Endogenous Compound];histone antibody/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];povidone iodine;sodium chloride;trientine/dt [Drug Therapy];ulobetasol propionate/dl [Intradermal Drug Administration],"Freg, G. N. I.;Shah, V.;Nagral, A.;Jhaveri, A.",2016,01 Mar,http://dx.doi.org/10.1016/j.jceh.2015.11.005,0,0,
1238,Wilson disease: Health-related quality of life and risk for depression,"Background: Wilson disease is an autosomal recessive disorder of copper metabolism and requires lifelong medical treatment. Therefore, the analysis of quality of life has gathered more attention. Aims of this study were to examine risk for depression and health-related quality of life in patients suffering from Wilson disease. Methods: Sixty-eight patients were included in this retrospective cross sectional study. The Personal Health Questionnaire-9 Depression Scale was used to assess depression. The Short Form-36 Health Survey questionnaire was used to assess health-related quality of life. Results: The Personal Health Questionnaire-9 indicated that 21% (14/68) of patients were at risk for major depressive disorders (scores > 10) and 35% (24/68) were at risk for mild depression (scores 5-9). Women had significantly lower life quality scores than men. Primary neurologic disease manifestation was associated with significantly lower total Short Form-36 and subdimension scores compared with primary hepatic or mixed presentation. Overall, patients with Wilson disease experienced higher quality of life than patients with other chronic liver diseases. Conclusions: As patients with Wilson disease have a high risk for depressive disorders, active assessment for depression is mandatory. Patients with primary neurological symptoms are at higher risk for reduction of life quality. Copyright © 2015 Elsevier Masson SAS.",adult;article;clinical article;cross sectional study;depression;female;human;major depression;male;neurologic disease;Patient Health Questionnaire;quality of life;risk factor;Short Form 36;Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc derivative/cb [Drug Combination];zinc derivative/dt [Drug Therapy],"Schaefer, M.;Gotthardt, D. N.;Ganion, N.;Wohnsland, S.;Seessle, J.;Stremmel, W.;Pfeiffenberger, J.;Weiss, K. H.",2016,01 Jun,http://dx.doi.org/10.1016/j.clinre.2015.09.007,0,0,
1239,The role of zinc in liver cirrhosis,"Zinc is an essential trace element playing fundamental roles in cellular metabolism. It acts mostly by binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Zinc is critical to a large number of structural proteins, enzymatic processes, and transcription factors. Zinc deficiency can result in a spectrum of clinical manifestations, such as poor of appetite, loss of body hair, altered taste and smell, testicular atrophy, cerebral and immune dysfunction, and diminished drug elimination capacity. These are common symptoms in patients with chronic liver diseases, especially liver cirrhosis. The liver is the main organ responsible for the zinc metabolism which can be affected by liver diseases. On the other hand, zinc deficiency may alter hepatocyte functions and also immune responses in inflammatory liver diseases. Liver cirrhosis represents the most advanced stage of chronic liver diseases and is the common outcome of chronic liver injury. It is associated with energy malnutrition, with numerous metabolic disorders, such as hypoalbuminemia, with imbalance between branched-chain amino acids and aromatic amino acids, and with reduced zinc serum concentrations. All these processes can influence the clinical outcome of patients, such ascites, hepatic encephalopathy and hepatocellular carcinoma. In the present review, we summarize the emerging evidence on the pitoval role of zinc in the pathogenesis of liver cirrhosis. Copyright © 2016, Fundacion Clinica Medica Sur. All rights reserved.",Cirrhosis complications;Zinc deficiency;apoptosis;ascites;cell compartmentalization;disease association;enzyme structure;human;liver cirrhosis;liver injury;liver metabolism;malnutrition;molecular docking;nonhuman;pathogenesis;protein secretion;review;Wilson disease;zinc metabolism;zinc/ec [Endogenous Compound],"Grungreiff, K.;Reinhold, D.;Wedemeyer, H.",2016,January-February,http://dx.doi.org/10.5604/16652681.1184191,0,0,
1240,Dermoscopy and direct immunofluorescence findings of elastosis perforans serpiginosa,"Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D-penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS. Copyright © 2016 British Association of Dermatologists",acne/dt [Drug Therapy];adult;article;case report;diagnostic equipment;drug withdrawal;elastosis/di [Diagnosis];elastosis/dt [Drug Therapy];elastosis/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];epidermis hyperplasia;epiluminescence microscopy;female;human;human tissue;immunofluorescence test;physical examination;priority journal;skin biopsy;topical treatment;Wilson disease/dt [Drug Therapy];adapalene/tp [Topical Drug Administration];benzoyl peroxide/tp [Topical Drug Administration];clindamycin/tp [Topical Drug Administration];corticosteroid/dt [Drug Therapy];corticosteroid/tp [Topical Drug Administration];imiquimod/tp [Topical Drug Administration];isotretinoin/dt [Drug Therapy];isotretinoin/po [Oral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Ramirez-Bellver, J. L.;Bernardez, C.;Macias, E.;Moya, L.;Molina-Ruiz, A. M.;Cannata Ortiz, P.;Requena, L.",2016,01 Aug,http://dx.doi.org/10.1111/ced.12882,0,0,
1241,Neurological manifestations in Wilson's disease -possible treatment options for symptoms,"Introduction: Wilson's disease (WD) is a neurodegenerative disorder that presents mainly with liver symptoms, but may be accompanied by various neurological manifestations. WD can be successfully treated with chelators or zinc salts to correct the abnormal copper metabolism, which usually improves both liver function and the neurological deficits; however, improvement in neurological deficits can take years. Patients may initially present with severe neurological deficits that affect activities of daily living. Consequently, therapy to alleviate the neurological symptoms is needed. Treatment choices are often based on experience with other disorders with symptoms clinically similar to WD. Areas covered: Apart from general recommendations on the anti-copper therapy and liver transplantation in patients with WD, no guidelines for managing the neurological symptoms exist. Based on mainly case reports, this review describes the most frequent neurological symptoms and their possible treatments. Expert opinion: There is no strong evidence regarding treatment of neurological disturbances in patients with WD. Several case studies indicate that drugs used to treat movement disorders such as tremor, parkinsonism, or dystonia may also alleviate these symptoms in patients with WD. In the case of severe, disabling, neurological symptoms, the treatment options for symptoms should always be discussed with the patient. Copyright © 2016 Informa UK Limited, trading as Taylor & Francis Group.",Chorea;Dystonia;Symptomatic neurological treatment;Tremor;Wilson's disease;autonomic dysfunction;chorea/dt [Drug Therapy];clinical feature;clinical trial;deterioration;dysarthria/th [Therapy];dysphagia;dystonia/dt [Drug Therapy];epilepsy/dt [Drug Therapy];headache;human;hypersalivation/dt [Drug Therapy];liver transplantation;muscle cramp;neurologic disease;palliative therapy;parkinsonism/dt [Drug Therapy];polyneuropathy;practice guideline;priority journal;pyramidal sign;relaxation training;restless legs syndrome;review;speech therapy;treatment planning;tremor/dt [Drug Therapy];Wilson disease/su [Surgery];amantadine/dt [Drug Therapy];anticonvulsive agent/dt [Drug Therapy];apomorphine/dt [Drug Therapy];atropine/dt [Drug Therapy];baclofen/dt [Drug Therapy];benzatropine/dt [Drug Therapy];biperiden/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];clonidine/dt [Drug Therapy];gabapentin/dt [Drug Therapy];levodopa/dt [Drug Therapy];modafinil/dt [Drug Therapy];oxcarbazepine/dt [Drug Therapy];primidone/dt [Drug Therapy];propranolol/dt [Drug Therapy];scopolamine/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy],"Litwin, T.;Dusek, P.;Czlonkowska, A.",2016,20 May,http://dx.doi.org/10.1080/21678707.2016.1188003,0,0,
1242,Essential medicines in the United States - Why access is diminishing,,acquired immune deficiency syndrome;amebiasis/dt [Drug Therapy];article;brain cancer/dt [Drug Therapy];Chagas disease/dt [Drug Therapy];chronic lymphatic leukemia/dt [Drug Therapy];commercial phenomena;cryptococcal meningitis/dt [Drug Therapy];cryptosporidiosis/dt [Drug Therapy];cystinuria/dt [Drug Therapy];drug approval;drug cost;drug industry;drug manufacture;drug marketing;drug research;echinococcosis/dt [Drug Therapy];food and drug administration;health care access;health care disparity;health care system;health program;Hodgkin disease/dt [Drug Therapy];human;Human immunodeficiency virus infection;hypertension/dt [Drug Therapy];latent tuberculosis/dt [Drug Therapy];leishmaniasis/dt [Drug Therapy];leprosy/dt [Drug Therapy];malaria/dt [Drug Therapy];morbidity;mortality;multidrug resistant tuberculosis/dt [Drug Therapy];multiple cancer/dt [Drug Therapy];neurocysticercosis/dt [Drug Therapy];onchocerciasis/dt [Drug Therapy];parasitosis/dt [Drug Therapy];pharmaceutical care;pneumocystosis/dt [Drug Therapy];pneumocystosis/pc [Prevention];prescription;priority journal;public health service;scabies/dt [Drug Therapy];schistosomiasis/dt [Drug Therapy];strongyloidiasis/dt [Drug Therapy];toxoplasmosis/dt [Drug Therapy];toxoplasmosis/pc [Prevention];tuberculosis/dt [Drug Therapy];United States;Wilson disease/dt [Drug Therapy];world health organization;albendazole/dt [Drug Therapy];albendazole/pe [Pharmacoeconomics];aminosalicylic acid/dt [Drug Therapy];benznidazole/dt [Drug Therapy];capreomycin/dt [Drug Therapy];chlorambucil/dt [Drug Therapy];clofazimine/dt [Drug Therapy];cycloserine/dt [Drug Therapy];dactinomycin/dt [Drug Therapy];dapsone/dt [Drug Therapy];essential drug;ethionamide/dt [Drug Therapy];flucytosine/dt [Drug Therapy];generic drug;ivermectin/dt [Drug Therapy];mebendazole;nitroprusside sodium/dt [Drug Therapy];paromomycin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pentamidine isethionate/dt [Drug Therapy];permethrin/dt [Drug Therapy];praziquantel/dt [Drug Therapy];procarbazine/dt [Drug Therapy];pyrazinamide/dt [Drug Therapy];pyrimethamine/dt [Drug Therapy];pyrimethamine/pe [Pharmacoeconomics];quinidine gluconate/dt [Drug Therapy];rifabutin/dt [Drug Therapy];rifapentine/dt [Drug Therapy];streptomycin/dt [Drug Therapy];sulfadiazine/dt [Drug Therapy],"Alpern, J. D.;Song, J.;Stauffer, W. M.",2016,19 May,http://dx.doi.org/10.1056/NEJMp1601559,0,0,
1243,White matter changes in Wilson's disease: A radiological enigma,"Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease.",Atypical magnetic resonance imaging;white matter changes;Wilson's disease;abnormal posture;absence of side effects/si [Side Effect];article;ataxic gait;basal ganglion;case report;ceruloplasmin blood level;child;clinical feature;cognitive defect;copper urine level;demyelinating disease/di [Diagnosis];differential diagnosis;drug dose titration;dystonia;electroencephalogram;epileptic discharge/di [Diagnosis];follow up;frontoparietal cortex;hand tremor;human;Kayser Fleischer ring;male;muscle rigidity;myoclonus;nuclear magnetic resonance imaging;occipital cortex;priority journal;school child;speech disorder;subacute sclerosing panencephalitis/di [Diagnosis];thalamus;urine level;vestibuloocular reflex;white matter lesion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];pyridoxine/ae [Adverse Drug Reaction];pyridoxine/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy],"Mukherjee, S.;Solanki, B.;Guha, G.;Saha, S. P.",2016,July-September,http://dx.doi.org/10.4103/0976-3147.176195,0,0,
1244,"Hepatolenticular degeneration: The comparative effectiveness of D-penicillamine, potassium sulfide, and diethyldithiocarbamate as decoppering agents",,comparative effectiveness;drug efficacy;genetic screening;health care access;human;liver disease;neurologic disease;note;priority journal;storage disease;Wilson disease/dt [Drug Therapy];copper;diethyldithiocarbamic acid/cm [Drug Comparison];diethyldithiocarbamic acid/dt [Drug Therapy];manganese;penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];potassium sulfate/cm [Drug Comparison];potassium sulfate/dt [Drug Therapy];trientine;zinc,"Hafberg, E. T.",2016,01 Jun,http://dx.doi.org/10.1016/j.jpeds.2015.12.040,0,0,
1245,"Chronic psychosis, delayed diagnosis and Wilson's disease",,adult;anxiety;article;bilirubin blood level;case report;caudate nucleus;chronic disease;delayed diagnosis;delusion;disease severity;dorsal striatum;echography;hand;human;impulsiveness;jaundice;male;medical history;mesencephalon;nuclear magnetic resonance imaging;pons;priority journal;proteinuria;psychosis;rest;schizophrenia/dt [Drug Therapy];spasticity;splenomegaly;tendon reflex;thalamus;tremor;visual hallucination;vivid dream;voice;Wilson disease;alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;hemoglobin/ec [Endogenous Compound];lorazepam/dt [Drug Therapy];olanzapine/dt [Drug Therapy];penicillamine/cb [Drug Combination];pyridoxine/cb [Drug Combination];quetiapine/dt [Drug Therapy];zinc acetate,"Maurya, P. K.;Kulshreshtha, D.;Singh, A. K.;Thakkar, M. D.;Thacker, A. K.",2016,01 May,http://dx.doi.org/10.1093/qjmed/hcv214,0,0,
1246,Metals and Neurodegeneration,"Metals play important roles in the human body, maintaining cell structure and regulating gene expression, neurotransmission, and antioxidant response, to name a few. However, excessive metal accumulation in the nervous system may be toxic, inducing oxidative stress, disrupting mitochondrial function, and impairing the activity of numerous enzymes. Damage caused by metal accumulation may result in permanent injuries, including severe neurological disorders. Epidemiological and clinical studies have shown a strong correlation between aberrant metal exposure and a number of neurological diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, autism spectrum disorders, Guillain-Barre disease, Gulf War syndrome, Huntington's disease, multiple sclerosis, Parkinson's disease, and Wilson's disease. Here, we briefly survey the literature relating to the role of metals in neurodegeneration. Copyright © 2016 Chen P et al.",Alzheimer disease;amyotrophic lateral sclerosis;autism;chelation therapy;cognitive defect;environmental exposure;Guillain Barre syndrome;human;Huntington chorea;long term exposure;multiple sclerosis;nerve degeneration;neurodegeneration with brain iron accumulation;neurotoxicity;nonhuman;occupational exposure;oxidative stress;Parkinson disease;Persian Gulf syndrome;prenatal exposure;protein aggregation;review;Wilson disease;aluminum;arsenic;cadmium/to [Drug Toxicity];copper/ec [Endogenous Compound];dimercaprol;edetate calcium disodium;ferric ferrocyanide;iron/ec [Endogenous Compound];lead/to [Drug Toxicity];manganese/ec [Endogenous Compound];metal/ec [Endogenous Compound];methylmercury;reactive oxygen metabolite/ec [Endogenous Compound];succimer;thallium/to [Drug Toxicity];zinc/ec [Endogenous Compound],"Chen, P.;Miah, M. R.;Aschner, M.",2016,,http://dx.doi.org/10.12688/f1000research.7431.1,0,0,
1247,Wilson's disease in Thai children between 2000 and 2012 at king chulalongkorn memorial hospital,"Objective: Wilson's disease (WD) is a rare autosomal recessive disorder characterized by copper accumulation. Clinical presentations are extraordinarily diverse, and currently no single diagnostic test can confirm WD with high accuracy. A complete understanding of the presentations and improved diagnostic methods are important for disease management. The authors' aimed to examine disease characteristics, management, and treatment outcome of WD in children, especially when genetic analysis and liver copper measurements were limited. Material and Method: Data was collected from 21 WD children who were treated at King Chulalongkorn Memorial Hospital between 2000 and 2012. Inclusion criteria followed the WD scoring system, where other liver diseases are ruled out systematically. Results: The mean age at diagnosis was 13.5+/-3.36 years, with 19 symptomatic patients, and two asymptomatic individuals who were diagnosed through family screening. Presentations varied, jaundice (52%), ascites (52%), edema (52%), Coombsnegative hemolytic anemia (14%), neurological abnormalities (33%), renal involvement (19%), and fulminant hepatic failure (5%). Based on the key parameters in WD scoring system, 14 patients (66%) had Kayser-Fleischer (KF) rings. Seventeen (89%) had low serum ceruloplasmin, and 20 (95%) had increased urinary copper excretion. These positive findings made WD scoring system accurately diagnose 66% of patients. Chelation therapy was the first line of therapy for all patients except one, who underwent liver transplantation. After therapy, liver function test returned to normal in all patients. However, neurological symptoms did not improve with combined drug therapy using chelating and neuropsychiatric agents. Conclusion: WD in children mostly affected the liver. WD was suspected in seven patients (34%), thus needed further investigation. Therefore, long-term follow-up in those with suspected WD is the appropriate method for diagnosis and management in limited diagnostic tests. We suggest further treatment, and use of clinical response to treatment, as a criterion for confirming the WD diagnosis. Copyright © 2016, Medical Association of Thailand. All rights reserved.",atp7b;Cirrhosis;Copper;Liver disease;Wilson's disease;adolescent;article;ceruloplasmin blood level;child;clinical article;copper blood level;evaluation and follow up;female;genetic analysis;human;liver function;male;outcome assessment;peripheral edema;proteinuria;school child;scoring system;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Sintusek, P.;Chongsrisawat, V.;Poovorawan, Y.",2016,February,,0,1,
1248,Chemical and physical characterization of thermal aggregation of model proteins modulated by zinc(II) and copper(II) ions,"BACKGROUND: Metal ions are implicated in protein aggregation processes of several neurodegenerative pathologies, where the protein deposition occurs, and in the biotechnology field like the food technology where many processes in food manufacturing are based on thermal treatments. OBJECTIVE: The influence of Cu<sup>2+</sup> or Zn<sup>2+</sup> ions on the thermal aggregation process of Bovine beta-lactoglobulin (BLG) and Bovine Serum Albumin (BSA), two protein models, was studied with the aim of delineating the role of these ions in the protein aggregation kinetics and to clarify the related molecular mechanisms. METHODS: The protein structure changes were monitored by Raman spectroscopy, whereas the aggregate growth was followed by Dynamic Light Scattering measurements. RESULTS: Both metal ions are able to favour the BLG aggregation, whereas only Zn<sup>2+</sup> ions have a promoter effect on the thermal aggregation of BSA. The reason of this different behaviour is that the BLG aggregation evolution is manly affected by the redistribution of charges, whereas that of BSA by the metal coordination binding which depends on metal. CONCLUSIONS: Raman spectroscopy, combined with dynamic light scattering experiments, was very useful in identifying the role played by Cu<sup>2+</sup> and Zn<sup>2+</sup> on the aggregation pathways of BLG and BSA. The results provide evidence for the role of histidine residues both in the redistribution of charges and in the two modes of metal binding that take place in BLG- and BSA-containing systems, respectively. Copyright © 2016 - IOS Press and the authors.",Beta-lactoglobulin;Bovine Serum Albumin (BSA);copper and zinc ions;dynamic light scattering;Raman spectroscopy;article;kinetics;Menkes syndrome;molecule;photon correlation spectroscopy;priority journal;protein aggregation;protein structure;Raman spectrometry;static electricity;Wilson disease;beta lactoglobulin;bovine serum albumin;cupric ion;zinc ion,"Torreggiani, A.;Navarra, G.;Tinti, A.;Di Foggia, M.;Militello, V.",2016,29 Mar,http://dx.doi.org/10.3233/BSI-160145,0,0,
1249,Elastosis perforans serpiginosa and Wilson disease: A rare but predictable consequence of long-term therapy with D-penicillamine. [Portuguese],"Elastosis perfurans serpiginosa is a rare perforating dermatosis found primarily in adolescents and young adults, characterized by transepidermal elimination of abnormal elastic fibers. The only drug known capable of inducing elastosis perfurans serpiginosa is D-penicillamine. We report the case of a 52 year-old woman with keratotic papules arranged in an annular pattern with central clearing and centrifugal growth, located in the anterior cervical region. The patient was chronically treated with D-penicillamine for Wilson disease. Lesion biopsy showed transepidermal elimination of thickened, eosinophilic, branched, sawtooth-like elastic fibers. The clinical and pathological findings were consistent with elastosis perfurans serpiginosa secondary to D-penicillamine. It is estimated that elastosis perfurans serpiginosa occurs in 1% of patients treated with D-penicillamine. By blocking directly or indirectly the desmosine cross-links between elastin molecules, D-penicillamine leads to the synthesis of abnormal dermal and extracutaneous elastic fibers. Elastosis perfurans serpiginosa may be the first manifestation of a multisystemic degenerative process of elastic connective tissue. Copyright © Ordem dos Medicos 2016.",Chelating agents/therapeutic use;Hepatolenticular degeneration;Penicillamine;Skin diseases/chemically induced;adult;animal tissue;article;case report;connective tissue disease;elastic fiber;elastosis/co [Complication];elastosis/di [Diagnosis];elastosis/et [Etiology];elastosis/si [Side Effect];elastosis perforans serpiginosa/co [Complication];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/et [Etiology];elastosis perforans serpiginosa/si [Side Effect];female;human;keratosis;middle aged;papule;Wilson disease/dt [Drug Therapy];desmosine/ec [Endogenous Compound];elastin/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Pinho, A.;Cardoso, J. C.;Gouveia, M.;Oliveira, H.",2016,March,http://dx.doi.org/10.20344/amp.6749,0,0,
1250,The entire spectrum of typical and atypical magnetic resonance imaging changes in a single case of Wilson's disease,,adult;basal ganglion;case report;central pontine myelinolysis/di [Diagnosis];ceruloplasmin blood level;disease course;disease duration;disease severity;dysarthria;dystonia;human;hypersalivation;letter;male;medical history;neuroimaging;nuclear magnetic resonance imaging;priority journal;rigidity;slurred speech;thalamus;treatment response;white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Roy, U.;Panwar, A.;Hussain, Z.;Biswas, D.",2016,April-June,http://dx.doi.org/10.4103/0976-3147.178653,0,0,
1251,Cortical cystic necrosis in wilson disease,,add on therapy;adolescent;akinesia;brain necrosis/di [Diagnosis];brain ventricle dilatation/di [Diagnosis];case report;deterioration;disease course;drug dose escalation;drug withdrawal;dysarthria;handwriting;human;hypersalivation;leukomalacia/di [Diagnosis];male;neuroimaging;note;nuclear magnetic resonance imaging;onset age;priority journal;symptom;tonic clonic seizure/dt [Drug Therapy];urine level;walking difficulty;Wilson disease/dt [Drug Therapy];etiracetam/cb [Drug Combination];etiracetam/dt [Drug Therapy];oxcarbazepine/cb [Drug Combination];oxcarbazepine/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trihexyphenidyl;zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Shetty, A. S.;Kashikar, R.;Nagral, A.;Wadia, P. M.",2016,March,http://dx.doi.org/10.1001/jamaneurol.2015.3595,0,0,
1252,Wilson's disease masquerading as mania,"Wilson's disease involves abnormal copper metabolism, with associated impairments in the liver/brain. While psychiatric symptoms have been reported in about 20% cases at presentation; mania as an initial manifestation is rare in this patient group.We report a case of a young female who was initially diagnosed as a case of mania; but who, on subsequent investigations, was proved to be a case of Wilson's disease. We discuss possible origins of the manic symptoms based on her MRI findings; and then describe certain aspects of its management including a need for cautious use of antipsychotics and beneficial effects of lithium. Copyright © 2015 Elsevier GmbH.",Disease;Lithium;Mania;Wilson's;article;case report;ceruloplasmin blood level;child;copper blood level;disease severity;female;grandiose delusion;hepatomegaly;human;icd-10;mania/dt [Drug Therapy];medical history;neuroimaging;nuclear magnetic resonance imaging;outcome assessment;physical examination;priority journal;school child;Wilson disease;Young Mania Rating Scale;alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];lithium/dt [Drug Therapy];olanzapine/dt [Drug Therapy];penicillamine;zinc sulfate,"Chatterjee, S. S.;Mitra, S.;Ram, J. R.",2016,01 Mar,http://dx.doi.org/10.1016/j.baga.2015.11.005,0,0,
1253,Penicillamine in interstitial lung disease: A timely remainder of an old foe,"Penicillamine-induced lung injury has been sparsely reported in the literature. We report one such case with its wide-ranging ramifications. We present an unusual case of drug induced-interstitial lung disease (DI-ILD) caused by penicillamine, resulting in acute lung injury in a young patient with Wilson's liver disease. Patient had a interstial lung disease which was attributed to the drug pencillamine. Penicillamine-induced lung injury has been sparsely reported in the literature and dose-dependent toxicity in a patient with neuro-psychiatric diseases adds to the rarity of the case. Furthermore, the complexities involved in diagnosing DI-ILD are deliberated. Copyright © 2016, Asian Journal of Pharmaceutical and Clinical Research. All rights reserved.",Interstitial lung disease;Penicillamine;Wilson's disease;adult;article;blood level;case report;clinical effectiveness;clinical feature;depression;differential diagnosis;disease association;drug efficacy;drug response;drug safety;drug tolerability;human;interstitial lung disease/dt [Drug Therapy];interstitial lung disease/si [Side Effect];lung function test;male;medical history;outcome assessment;patient assessment;syndrome delineation;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;corticosteroid/dt [Drug Therapy];corticosteroid/ih [Inhalational Drug Administration];methylprednisolone/dt [Drug Therapy];methylprednisolone/pa [Parenteral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Pawadshettar, S.;Acharya, V. K.;Arun, M.;Unnikrishnan, B.;Tantry, B. V.",2016,January,,0,0,
1254,High-precision isotopic analysis of essential mineral elements in biomedicine: Natural isotope ratio variations as potential diagnostic and/or prognostic markers,"High-precision isotopic analysis of essential mineral elements, mainly Ca, Cu, Fe and Zn, provides relevant biomedical information. For this application, multi-collector ICP-mass spectrometry is the preferred technique. Variation in the isotopic signature of these elements is governed by alterations in their uptake, metabolism and/or excretion. Therefore, diseases that affect mineral metal metabolism, such as hemochromatosis, cancer, liver cirrhosis and Wilson's disease, affect the isotopic composition of these elements in some body compartments. This review discusses how natural isotope ratio variations in biofluids can potentially be exploited as alternative approaches for the diagnosis of diseases that can otherwise only be established at a later stage or via a more invasive method and/or for prognostic purposes. This discussion also includes an evaluation of the isotopic variability in biofluids for apparently healthy individuals and in biofluids, soft tissues and bone of experimentally controlled animals. Physiological and lifestyle factors were also paid attention to. Copyright © 2015 Elsevier B.V..",Biomedical applications;Bone mineral balance;Cancer;Essential elements;Isotopic analysis;Liver cirrhosis;mc-icp-ms;Metabolism;Metals;Natural isotope ratio variations;anemia;blood analysis;bone mineral;breast cancer;calcium blood level;copper blood level;diagnostic value;erythrocyte level;hemochromatosis;high precision isotopic analysis;human;iron blood level;isotope analysis;liver cell carcinoma;mass spectrometry;nonhuman;Parkinson disease;priority journal;prognosis;review;urinalysis;Wilson disease;calcium/ec [Endogenous Compound];copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];mineral/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Costas-Rodriguez, M.;Delanghe, J.;Vanhaecke, F.",2016,February 01,http://dx.doi.org/10.1016/j.trac.2015.10.008,0,0,
1255,Serum Copper and Zinc in a Representative Sample of Bulgarian Population,"Copper (Cu) and zinc (Zn) are essential for life. Body Cu and Zn content depends on variety of factors-age, gender, and diet, type of drinking water, geographical location and genetic predisposition. Copper status becomes even more relevant not only in rare genetic disorders such as Wilson disease but in diseases such as cardiovascular ones, impaired glucose tolerance and neuro-degenerative and tumor diseases. The study aimed to examine the distribution of serum Cu and Zn in a representative group of the Bulgarian population and to describe factors which influence metal content. It also aimed to describe the link between serum Cu levels and the frequency of Alzheimer's disease (AD) in Bulgarians. Cu and Zn in serum were measured in 379 individuals (172 males and 207 females) from 5 different regions in Bulgaria by flame atomic absorption using AAnalyst 400, Perkin Elmer. Statistical analyses were performed by SPSS, 19. Median and inert-quartile range (IQR) for blood Cu were 15.89 (13.87-7.89) mumol/L and for Zn-13.00 (11.7-14.68) mumol/L in the examined group. Higher Cu levels in females than in males were found (p < 0.001). Decrease of Zn with aging was established (p > 0.05). Significant difference (p < 0.05) was found in serum Cu between young people (< 30 year old) and adults over 61 year old. Statistically significant difference in Cu and Zn was observed (p < 0.05) in respect of residences. Difference without significance was measured between serum lipids and serum Cu (p = 0.541) and Zn (p = 0.741).",Alzheimer's disease;copper;trace elements;zinc;adult;alcohol consumption;Alzheimer disease;article;atomic absorption spectrometry;Bulgarian (people);cholesterol blood level;controlled study;copper blood level;female;human;hyperlipidemia;male;middle aged;normal human;physical activity;questionnaire;vein puncture;zinc blood level;copper/ec [Endogenous Compound];high density lipoprotein cholesterol/ec [Endogenous Compound];low density lipoprotein cholesterol/ec [Endogenous Compound];triacylglycerol/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Ivanova, I.;Atanasova, B.;Kostadinova, A.;Bocheva, Y.;Tzatchev, K.",2016,01 Oct,http://dx.doi.org/10.1515/amb-2016-0013,0,0,
1256,A case of wilson's disease presenting as chronic liver disease,"Wilson's disease is one of the most common inherited liver diseases with a worldwide incidence of 10-30 million cases. The increased frequency in certain countries is due to high rates of consanguinity and the fulminant presentation of the disease is more common in females than in males. It is an autosomal-recessive disorder caused by mutation in the ATP7B gene, with resultant impairment of biliary excretion of copper. Subsequent copper accumulation, first in the liver but later on in the brain and other tissues, produces clinical manifestations that may include hepatic, neurological, psychiatric, ophthalmological and other derangements. Genetic testing is impractical because of the multitude of mutations that have been identified, so accurate diagnosis relies on judicious use of laboratory and other diagnostic tests. Lifelong palliative treatment with a different combination of medications, or with liver transplantation if needed, can successfully ameliorate or prevent the progressive deterioration of the disease, otherwise death would inevitably ensue. Since effective treatment is available for this disease, early and correct daignosis is very important. Here, we report a case of Wilson's disease in a 15-year-old girl presenting to us as chronic liver disease. Copyright © 2016, Ibn Sina Trust. All rights reserved.",ATP7B gene;Autosomal recessive;Chronic liver disease;Mutation;Wilson's disease;abdominal pain;adolescent;anemia;arthralgia/si [Side Effect];article;aspiration;case report;chelation therapy;clinical feature;consciousness disorder;convulsion;diet restriction;disease association;disorientation;drug hypersensitivity/si [Side Effect];female;fever/si [Side Effect];human;inguinal hernia;jaundice;loss of appetite;nausea;pancytopenia;rash/si [Side Effect];resuscitation;splenomegaly;tonic clonic seizure;vomiting;Wilson disease;copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/po [Oral Drug Administration];zinc/po [Oral Drug Administration],"Nayeem, M.;Bulbul, S.;Zabeen, N.;Islam, M. N.;Sobur, M. A.;Haque, M. A.",2016,,http://dx.doi.org/10.3329/bjms.v15i3.30203,0,0,
1257,Wilson's disease: Atypical imaging features,"Wilson's disease is a genetic movement disorder with characteristic clinical and imaging features. We report a 17-year-old boy who presented with sialorrhea, hypophonic speech, paraparesis with repeated falls and recurrent seizures along with cognitive decline. He had bilateral Kayser Flescher rings. Other than the typical features of Wilson's disease in cranial MRI, there were extensive white matter signal abnormalities (T2 and FLAIR hyperintensities) and gyriform contrast enhancement which are rare imaging features in Wilson's disease. A high index of suspicion is required to diagnose Wilson's disease when atypical imaging features are present. Copyright © 2016, Australasian Medical Journal Pty Ltd. All rights reserved.",Copper storage disorders;Hepato-lenticular degeneration;mri;Neuroimaging;Wilson's disease;adolescent;article;behavior disorder;case report;genetic disorder;human;hypersalivation;leukodystrophy;male;nuclear magnetic resonance imaging;paraplegia;speech disorder;storage disease;urine incontinence;Wilson disease/di [Diagnosis];penicillamine;zinc,"Vishnu, V. Y.;Modi, M.;Goyal, M. K.;Vyas, S.;Lal, V.",2016,,http://dx.doi.org/10.4066/AMJ.2016.2774,0,0,
1258,Liver disease resulting from metabolic diseases. Haemochromatosis. Wilson's disease. Alpha-1 antitrypsin deficiency,"Introduction Hemochromatosis, Wilson's disease and alpha-1-antitrypsin deficiency are the main metabolic liver diseases. Hemochromatosis Patients with hemochromatosis develop a progressive iron overload that leads to liver cirrhosis. Its diagnosis is based in the confirmation of iron overload and the study of mutations of HFE gene. Phlebotomy is the treatment of choice for hemochromatosis; it avoids the progression to cirrhosis. Wilson's disease Wilson's disease is due to mutations in the ATP7B. Its main feature is copper overload that causes liver toxicity (fulminant hepatic failure or cirrhosis) and neurotoxicity. Drugs used for treatment of Wilson's disease are D-penicillamine, trientine and zinc. Alpha-1-antitrypsin deficiency Patients with alpha-1-antitrypsin deficiency develop liver disease (neonatal cholestatic hepatitis and/or chorinic liver disease) and emphysema as a consequence of the retention in the liver and the reduction of serum levels of the enzyme. There is no specific treatment for liver disease due to alpha-1-antitrypsin deficiency. Copyright © 2016",Alpha-1 antitrypsin deficiency;Haemochromatosis;Wilson's disease;alpha 1 antitrypsin deficiency;article;cholestatic hepatitis;chronic liver disease;copper overload;fulminant hepatic failure;gene mutation;hemochromatosis/di [Diagnosis];hemochromatosis/su [Surgery];HFE gene;human;intoxication;iron overload;liver cirrhosis;mutator gene;neurotoxicity;phlebotomy;Wilson disease/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Santos, J. I. H.",2016,01 May,http://dx.doi.org/10.1016/j.med.2016.05.002,0,0,
1259,The copper rush of the nineties,"The nineties witnessed the discovery of the copper ATPases, enzymes which transport copper across the cytoplasmic membranes of bacteria and eukaryotes. In the same decade, several other key components of copper homeostasis have also been discovered, like copper chaperones and plasma membrane copper transporters. This has finally led to a molecular understanding of two inherited human diseases related to copper: Menkes disease, manifested by systemic copper deficiency, and Wilson disease, caused by defective secretion of excess copper. A historic perspective and untold stories of the events leading up to these discoveries are presented here. Copyright © 2016 The Royal Society of Chemistry.",ataxia;cell membrane;chloroplast;copper deficiency;copper metabolism;enzyme synthesis;eukaryote;human;Menkes syndrome;mitochondrion;molecular cloning;nonhuman;priority journal;regulatory mechanism;review;sheep disease;systemic disease;Wilson disease;carrier proteins and binding proteins;copper derivative;copper exporting adenosine triphosphatase;ctr1 protein;metallochaperone;microRNA;natural resistance associated macrophage protein 2;tetrathiomolybdic acid;trace element;unclassified drug;zinc,"Solioz, M.",2016,September,http://dx.doi.org/10.1039/c6mt00111d,0,0,
1260,Cardiac arrhythmia in Wilson's disease: An oversighted and overlooked entity!,"Wilson's disease is a multisystem disorder which manifests with hepatic, neurological, musculoskeletal, hematological, renal, and cardiac symptoms. The hepatic and neurological manifestations often overshadow the other system involvement including cardiac symptoms and signs, which may prove fatal. We report a case of a young female who presented with progressive parkinsonian features and dystonia for around 4 months followed 2 months later by the complaint of episodes of light-headedness. She was diagnosed to have Wilson's disease based on the presence of Kayser-Fleischer ring and laboratory parameters of copper metabolism. Electrocardiography of the patient incidentally revealed 2<sup>nd</sup> degree Mobitz type-1 atrioventricular block explaining her episodes of light-headedness. She was started on penicillamine and trihexyphenidyl. The heart block improved spontaneously. Cardiac autonomic function tests including blood pressure response to standing and heart rate response to standing were observed to be normal. We review the literature on cardiac manifestations of Wilson's disease and emphasize that patients with Wilson's disease should be assessed for cardiac arrhythmia and cardiac dysfunction as these may have therapeutic and prognostic implications. Copyright © 2016 Journal of Neurosciences in Rural Practce.",Autonomic function;cardiac arrhythmia;heart block;hepatolenticular degeneration;Wilson's disease;adolescent;article;blurred vision;bradykinesia;brain damage/di [Diagnosis];brain damage/dt [Drug Therapy];case report;comorbidity;computer assisted tomography;consanguineous marriage;daily life activity;disease duration;dizziness;dysarthria;dystonia/dt [Drug Therapy];echography;eye disease/di [Diagnosis];eye examination;face disorder;female;heart arrhythmia/di [Diagnosis];Holter monitoring;human;hypophonia;jaundice;Kayser Fleischer ring/di [Diagnosis];leukocyte count;priority journal;slit lamp;splenomegaly/di [Diagnosis];thrombocyte count;weakness;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy],"Bajaj, B.;Wadhwa, A.;Singh, R.;Gupta, S.",2016,October-December,http://dx.doi.org/10.4103/0976-3147.186982,0,0,
1261,Successful treatment of Wilson disease-associated IgA pemphigus with IVIG,,acantholysis;adult;case report;drug efficacy;drug safety;drug substitution;drug withdrawal;eye examination;heavy metal blood level;human;hypertransaminasemia;IgA pemphigus/dt [Drug Therapy];letter;liver biopsy;liver cirrhosis;low drug dose;male;priority journal;pustule;remission;scalp pruritus;skin defect;treatment outcome;treatment response;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;copper/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];immunoglobulin/dt [Drug Therapy];immunoglobulin/iv [Intravenous Drug Administration];immunoglobulin A antibody/ec [Endogenous Compound];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Iskandarli, M.;Gerceker Turk, B.;Ertam, I.;Yaman, B.;Ozturk, G.",2016,,http://dx.doi.org/10.1111/jdv.13106,0,0,
1262,Diagnosis and Management of Tremor,"Purpose of Review: Tremor, which is a rhythmic oscillation of a body part, is among the most common involuntary movements. Rhythmic oscillations may manifest in a variety of ways; as a result, a rich clinical phenomenology surrounds tremor. For this reason, diagnosing tremor disorders can be particularly challenging. The aim of this article is to provide the reader with a straightforward approach to the diagnosis and management of patients with tremor. Recent Findings: Scientific understanding of the pathophysiologic basis of tremor disorders has grown considerably in recent years with the use of a broad range of neuroimaging approaches and rigorous, controlled postmortem studies. The basal ganglia and cerebellum are structures that seem to play a prominent role. Summary: The diagnosis of tremor disorders is challenging. The approach to tremor involves a history and a neurologic examination that is focused on the nuances of tremor phenomenology, of which there are many. The evaluation should begin with a tremor history and a focused neurologic examination. The examination should attend to the many subtleties of tremor phenomenology. Among other things, the history and examination are used to establish whether the main type of tremor is an action tremor (ie, postural, kinetic, or intention tremor) or a resting tremor. The clinician should then formulate two sets of differential diagnoses: disorders in which action tremor is the predominant tremor versus those in which resting tremor is the main tremor. Among the most common of the former type are essential tremor, enhanced physiologic tremor, drug-induced tremor, dystonic tremor, orthostatic tremor, and cerebellar tremor. Parkinson disease is the most common form of resting tremor, along with drug-induced resting tremor. This article details the clinical features of each of these as well as other tremor disorders. © Copyright 2016 by the American Academy of Neurology.",cerebellar tremor;differential diagnosis;disease association;drug induced action tremor;drug induced resting tremor;dystonic tremor;enhanced physiologic tremor;essential tremor;fragile x tremor ataxia syndrome;human;immunosuppressive treatment;medical history;midbrain tremor;motor dysfunction;neurologic examination;orthostatic tremor;Parkinson disease;peripheral neuropathy;physical examination;primary writing tremor;psychogenic tremor;review;tremor/di [Diagnosis];Wilson disease;acetazolamide;alprazolam;amantadine;baclofen;benzodiazepine derivative;botulinum toxin;carbamazepine;carbidopa plus levodopa;clonazepam;cyclophosphamide;ethosuximide;gabapentin;immunoglobulin;levodopa;phenytoin;pregabalin;primidone;propranolol;tetrathiomolybdic acid;topiramate;trientine;zinc,"Louis, E. D.",2016,01 Aug,http://dx.doi.org/10.1212/CON.0000000000000346,0,0,
1263,Acute liver failure because of wilson disease with overlapping autoimmune hepatitis features: The coexistence of two diseases?,,acute liver failure/co [Complication];acute liver failure/et [Etiology];adolescent;ammonia blood level;antibiotic prophylaxis;ascites;autoimmune hepatitis;blood clotting disorder;blood transfusion;case report;cell infiltration;Coombs test;disease course;DNA determination;drug dose increase;female;gene mutation;hemolytic anemia;hepatitis A;hepatitis B;hepatitis C;human;human tissue;jaundice;laboratory test;leg edema;liver function test;liver transplantation;medical history;nuclear magnetic resonance imaging;phenotype;physical examination;plasmapheresis;priority journal;short survey;slit lamp;thrombocytopenia;Wilson disease;aminotransferase/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];autoantibody/ec [Endogenous Compound];biological marker/ec [Endogenous Compound];immunoglobulin G/ec [Endogenous Compound];penicillamine;prednisone;Wilson disease protein/ec [Endogenous Compound],"Loudianos, G.;Zappu, A.;Lepori, M. B.;Dessi, V.;Mameli, E.;Orru, S.;Podda, R. A.;De Virgiliis, S.",2016,26 Jul,http://dx.doi.org/10.1097/MPG.0000000000000557,0,0,
1264,Wilson's disease: An update. [German],"Wilson's disease is an autosomal recessive genetic disorder in which ATP7B mutations lead to a dysfunction of the copper metabolism. A reduced excretion of copper into the bile and excessive copper deposition in the liver and brain are the consequence. Patient's with WD typically present with hepatic symptoms in late childhood or adolescence, or as young adults with extrapyramidal or psychiatric symptoms. However, it is important to consider WD also in patients with movement disorders after 40 years of age, particularly in combination with a (sub)clinical hepatic dysfunction. If untreated WD results in severe disability or death. If diagnosed at an early stage effective treatment is available that will prevent disease progress and reverse some of the symptoms. Treatment with chelating agents induces renal copper excretion, and zinc salts inhibit duodenal copper resorption. Liver transplant is reasonable in severe hepatic cases and is also considered for a severe neurological course which cannot be successfully treated otherwise. Copyright © Schattauer 2016.",atp7b;Chelating agents;Copper;article;brain metabolism;copper metabolism;disability severity;early diagnosis;extrapyramidal syndrome;human;liver dysfunction;liver metabolism;mental disease;motor dysfunction;small intestine absorption;symptom;urinary excretion;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Voss, H.",2016,,,0,0,
1265,Elemental bioimaging and speciation analysis for the investigation of Wilson's disease using muxRF and XANES,"A liver biopsy specimen from a Wilson's disease (WD) patient was analyzed by means of micro-X-ray fluorescence (muXRF) spectroscopy to determine the elemental distribution. First, bench-top muXRF was utilized for a coarse scan of the sample under laboratory conditions. The resulting distribution maps of copper and iron enabled the determination of a region of interest (ROI) for further analysis. In order to obtain more detailed elemental information, this ROI was analyzed by synchrotron radiation (SR)-based muXRF with a beam size of 4 mum offering a resolution at the cellular level. Distribution maps of additional elements to copper and iron like zinc and manganese were obtained due to a higher sensitivity of SR-muXRF. In addition to this, X-ray absorption near edge structure spectroscopy (XANES) was performed to identify the oxidation states of copper in WD. This speciation analysis indicated a mixture of copper(i) and copper(ii) within the WD liver tissue. Copyright © 2016 The Royal Society of Chemistry.",article;human;human tissue;liver;liver biopsy;oxidation;priority journal;sensitivity analysis;synchrotron radiation;Wilson disease;X ray absorption near edge structure spectroscopy;X ray absorption spectroscopy;X ray fluorescence;copper;iron;manganese;zinc,"Hachmoller, O.;Buzanich, A. G.;Aichler, M.;Radtke, M.;Dietrich, D.;Schwamborn, K.;Lutz, L.;Werner, M.;Sperling, M.;Walch, A.;Karst, U.",2016,July,http://dx.doi.org/10.1039/c6mt00001k,0,0,
1266,Zinc monotherapy in young children with asymptomatic Wilson's disease: Multicenter study in Japan,"Background and Aims: AASLD and EASL guidelines recommend zinc monotherapy as a treatment for asymptmoatic patients with Wilson disease (WD). We previously reported that a reasonable goal in treating young children with asymptomatic WD using zinc to be maintaining 24-hour urinary copper excretion between 1 and 3 mug/kg/day for the first 1-2 years (Mizuochi, et al. JPGN 2011;53:365). Here, we aimed at evaluating long-term efficacy and safety of zinc monotherapy for young children, under 10 years old, with asymptomatic WD in Japanese pediatric centers and establishing appropriate benchmarks of maintenance therapy. Methods: We performed a retro-and prospective study to examine 21 children (median age 6 years, range 1-9) who satisfied diagnostic criteria for WD and were treated solely with zinc acetate prior to symptom onset at 10 participating pediatric centers in Japan. No additional WD sequelas, such as jaundice, hepatomegaly, or neurologic abnormalities were noted. We monitored serum AST and ALT, nonceruloplasmin serum copper, and 24-hour urinary copper for 1-7 years after initiation of zinc monotherapy. Additional monitorings included white blood cell count, hemoglobin, platelet count, gamma-glutamyltransferase, total bilirubin, albumin, iron, amylase, lipase, and prothrombin time, as well as 24-hour urinary zinc excretion. We performed abdominal ultrasonograpy and evaluated clinical WD manifestations, drug compliance, and adverse effects of zinc. The prescribed dosage of zinc acetate for patient <= 5 years was 25 mg twice daily; for those children 6 years or older, the dose was 25mg 3 times daily. We increased the dosage of zinc if the patients had AST/ALT > 50-70 U/L, and decreased it if they had adverse effects of zinc such as iron-deficiency anemia or pancytopenia. Results: At time of diagnosis, AST/ALT and 24-hour urinary copper were 148+/-118/234+/-151 U/L and 124+/-54 mug/day (5.8+/-2.9 mug/kg/day), respectively. All patients continued to take zinc without any evidence of zinc toxicity. None of our 21 patients became clinically symptomatic. AST/ALT significantly decreased to 54+/-30/77+/-49 U/L (P<0.001) at 1 month after initiation of treatment and was mostly maintained under 50 U/L for 1-7 years (AST/ALT: 33+/-7/38+/-17 and 29+/-5/34+/-6 U/L at 1 and 7 years after initiation of treatment, respectively). Twenty four-hour urinary copper significantly decreased to 49+/-21 mug/day (2.2+/-1.1 mug/kg/day; P<0.001) at 6 months after initiation of treatment and was mostly maintained under 75 mug/day and between 1 and 3 mug/kg/day for the remainder of the study (2.2+/-0.6 and 1.5+/-0.2 mug/kg/day at 1 and 7 years after initiation of treatment, respectively). Conclusions: Long-term zinc monotherapy for young children with asymptomatic WD proved highly effective and safe. A reasonable goal in treating young children with asymptomatic WD using zinc appears to be maintaining both AST/ALT under 50 U/L and 24-hour urinary copper excretion between 1 and 3 mug/kg/day (and under 75 mug/day).",adverse drug reaction;child;clinical article;clinical trial;comparative effectiveness;congenital malformation;controlled clinical trial;controlled study;copper blood level;diagnosis;drug therapy;hepatomegaly;human;human tissue;iron deficiency anemia;Japan;jaundice;leukocyte count;maintenance therapy;medication compliance;monitoring;monotherapy;multicenter study;nervous system;pancytopenia;pediatric hospital;pharmacokinetics;preschool child;prospective study;prothrombin time;safety;school child;side effect;symptom;thrombocyte count;toxicity;Wilson disease;zinc urine level;albumin;amylase;bilirubin;endogenous compound;gamma glutamyltransferase;hemoglobin;iron;triacylglycerol lipase;zinc;zinc acetate,"Mizuochi, T.;Eda, K.;Takaki, Y.;Iwama, I.;Araki, M.;Inui, A.;Hara, S.;Kumagai, H.;Hagiwara, S. I.;Murayama, K.;Murakami, J.;Kodama, H.",2016,October,http://dx.doi.org/10.1097/01.mpg.0000503536.79797.66,0,0,
1267,Serum zinc discriminate indeterminate: Acute liver failure from Wilson's disease: Acute liver failure,"Objectives and Study: Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. Combined clinical and laboratory findings are needed for early diagnosis. There is the hypothesis suggested that low serum Zinc (Zn) is related to phenotypic severity of WD. Indeed, alkaline phosphatase (ALP), a Zn-containing metallo-enzymes that reflects the real Zn deficiency is relatively low in WD patients might support this presumption. However, few studies underscore the role of these biomarkers in WD pathogenesis and severity. Our study aimed to observe the values of serum Zn, ALP and other baseline laboratory results in acute liver failure (ALF) of indeterminate cause and WD. Patients and Methods: The medical records from children with WD (n=43) and ALF of indeterminate cause (n=9) at King's College Hospital between 2005 and 2015 were retrospectively reviewed. All WD children had disease causing mutations identified. WD is classified into WD-non-ALF (n=28) and WD-ALF (n=15). The values of serum Zn, copper, ceruloplasmin (CP) and liver function tests were collected. Free serum copper and corrected Zn formula were calculated as following; Free copper (mu mol/L) total copper (mu mol/L)-bound copper (mu mol/L) (Bound copper 0.0472 x ceruloplasmin (mg/L)) and Corrected Zn patient 0.25xZn normal + ((albumin normal/albumin patient) x (Zn patient-(0.25x Zn normal)) Results: Our study demonstrates, a significantly lower level of serum Zn, corrected Zn and ALP in WD-ALF compare to WD non-ALF and ALF of indeterminate cause (Table 1). Conclusion: The present study showed that the dramatic aberrance of serum Zn in WD-ALF can discriminate WD-ALF from indeterminate ALF.",acute liver failure;chemical binding;child;clinical article;college;controlled study;copper blood level;genetic predisposition;human;human tissue;liver function test;medical record;mutation;Wilson disease;zinc blood level;zinc deficiency;albumin;alkaline phosphatase;ceruloplasmin;endogenous compound,"Sintusek, P.;Dhawan, A.",2016,October,http://dx.doi.org/10.1097/01.mpg.0000503536.79797.66,0,0,
1268,Modality of treatment and potential outcome of wilson's disease in Taiwan: A population-based longitudinal study,"Purpose: This study aimed to investigate the epidemiology, the preference of medication, and the long-term outcome of Wilson's disease in Taiwan. Methods: Data was obtained from the National Health Insurance Research Database (NHIRD), which stores detailed clinical records of all insurers in Taiwan. The database used in this study is a randomized sample of twomillion out of 23million beneficiaries in Taiwan's NHIRD in 2005. And the integrated medical records of these two-million cases were collected from 2000 to 2011. Subjects of Wilson's disease were identified as those with International Classification of Diseases, Ninth Revision (ICD-9) code 275.1 and the specific prescription drugs (including D-penicillamine, zinc, and trientine) in either outpatient clinic or inpatient records. Results: During the study period, 66 cases of Wilson's disease were identified. The male to female ratio was 1.75. The average prevalence rate was 1.81 per 100,000 and the average annual incidence rate was 0.22 per 100,000. The age-specific incidence rate peaked at 10-14 years of age, followed by 20-24 years, and 25-29 years. 54 of all subjects (81.8%) started the treatment with D-penicillamine, compared with zinc (12.1%) and trientine (6.1%). Among these 66 cases with Wilson's disease, 27 (40.9%) had liver cirrhosis and 3 (4.5%) underwent liver transplantation due to liver failure. Conclusions: D-penicillamine is still the drug most prescribed for patients with Wilson's disease, followed by zinc monotherapy. Although chronic liver injury cannot be avoided, a favorable long-term outcome is well demonstrated in this population-based study. Liver failure or mortality was rarely found.",adolescent;clinical trial;controlled clinical trial;controlled study;data base;drug therapy;female;hospital patient;human;icd-9;incidence;liver cirrhosis;liver failure;liver injury;liver transplantation;longitudinal study;major clinical study;male;medical record;monotherapy;mortality;national health insurance;outpatient department;prevalence;randomized controlled trial;Taiwan;Wilson disease;penicillamine;prescription drug;trientine;zinc,"Tai, C. S.;Ni, Y. H.",2016,October,http://dx.doi.org/10.1097/01.mpg.0000503536.79797.66,0,1,
1269,A Japanese child with idiopathic copper toxicosis,"We experienced a Japanese child with idiopathic copper toxicosis (ICT), who was diagnosed with special features of liver histology. Case: A seven-year-old boy was referred to our hospital because of a deep jaundice. He was suffering from itching and growth retardation since 3 years of age. His physical findings were jaundice, angioma spider on his cheeks, hepatospolenomegaly (liver palpable 6 cm in right costal margin, spleen palpable 5 cm in left costal margin), and scratches with bleeding in skin. His laboratory findings were WBC 6,420/micro L, hemoglobin 10.3 g/dL, platelet 174,000/micro L, total bilirubin 13.5 mg/dL, direct bilirubin 10.6 mg/dL, AST 1,477 U/L, ALT 457 U/L, LDH 393 U/L, GGT 162 U/L, Alb 2.9 g/dL, UA 2.4 mg/dL, PT 37.7%, APTT 49.4 sec, and haptoglobin 9mg/dL. His copper associated profiles were serum Cu 215 micro g/dL, ceruloplasmin 48.6 mg/dL, and 24-hour urine Cu 472.8 micro g/d. Clinical Course: He was diagnosed with Wilson's disease (WD) with normal serum ceruloplasmin level and no abnormality of ATP7B gene. He was treated with trientine hydrochloride in addition to zinc acetate for 30 days. His 24-hour urine Cu levels were increased to >2,500 micro g/d, while his condition was deteriorating. His new Wilson Index reached up to 17. He was transferred to the Transplantation Center and underwent cadaveric liver transplantation. Histology of explanted liver: Liver surface and divided face showed multiple nodular formations. Lobular architecture was disturbed with severe fibrosis. Inflammation was minimal. Mallory body like materials was markedly found in hepatocytes. A copper content in the explanted liver was 1482.3 micro g/g dry weight. Both Orcein and Rhodanine stainings were strongly stained in hepatocytes. Discussion and Conclusion: ICT is one of the copper metabolic disorders, less recognized than Wilson's disease. The pathogenesis of ICT is still unknown, but the clinical features of ICT are similar to hepatic type of Wilson's disease. Cases of Wilson's disease with normal or high level of serum ceruloplasimin should consider ICT. The liver histology is helpful to diagnose ICT.",angioma;bleeding;case report;ceruloplasmin blood level;cheek;child;clinical feature;congenital malformation;diagnosis;dry weight;fibrosis;growth retardation;hospital;human;human tissue;inflammation;intoxication;Japanese (citizen);jaundice;liver cell;liver histology;liver transplantation;male;Mallory body;nonhuman;partial thromboplastin time;preschool child;pruritus;school child;skin;spider;spleen;thrombocyte;urine;Wilson disease;bilirubin glucuronide;ceruloplasmin;endogenous compound;gamma glutamyltransferase;haptoglobin;hemoglobin;rhodanine;trientine;Wilson disease protein;zinc acetate,"Inui, A.;Umetsu, S.;Sogo, T.;Komatsu, H.;Fukuda, A.;Kasahara, M.;Matsuuta, A.;Fujisawa, T.",2016,October,http://dx.doi.org/10.1097/01.mpg.0000503536.79797.66,0,0,
1270,Analysis of renal impairment in 102 children with Wilson's disease,"a. Objectives Since the diverse manifestations of renal impairment appear in different periods of Wilson's disease(WD), misdiagnosis is not rare. We carried out this study to find the clinical features of renal impairment in children with WD. b. Methods We enrolled 102 children with WD who had been treated at our department from January 1995 to December 2012. Renal impairment is enclosed one of followings: abnormal urinalysis (proteinuria1/4hematuria,glucosuria, hypercalcinuria or increase of urine NAG; abnormal renal function (BUN>=7.14 mmol/L, Scr>=176.8 mol/L); abnormal renal ultrasound or kidney biopsy; excluding renal involvement caused by other factors. c. Results Demographic data: There are 58 with abnormal urine analysis in 102 WD patients. Excluded 14 with only once and 10 with D-penicillamine treatment, the remaining 34 patients: 14 boys and 20 girls.The disease course ranged from 3 days to 10 years. Clinical presentations:14 had hematuria, 4 had proteinuria and 15 had both proteinuria and hematuria,2 cases were nephrotic proteinuria, 1 case was renal tubular acidosis. Urine NAG increased in 12, urine RBC phase morphology was detected in 15, 3 glomerular hematuria and 12 non-glomerular. 1 patient's urine calcium increased. Serum creatinine clearance rate decreased in 2 patients. Bultrasound revealed asystematic kidney damages in 5 of 27 patients. Kidney biopsy showed IgA deposit in mesangial region in 2. Initial renal impairment:9 had initiated symptoms of renal impairment, 4 of them had gross hematuria, 1 with edema, hematuria and proteinuria,1 with purpura, hematuria and proteinuria,1 with frequent and urgent urination, 2 with edema and severe proteinuria. Prognosis:All patients' renal impairment were improved or disappeared after treatment. d. Conclusions Renal impairment with WD, including injury after D-penicillamine treatment are not rare. Themanifestations of renal impairment with WD are varied. Early diagnosis may bring them better prognosis. 10 - Glomerulonephritis, lupus, vasculitis.",adverse drug reaction;calcium urine level;child;clearance;clinical feature;clinical trial;controlled study;creatinine blood level;demography;drug therapy;early diagnosis;edema;female;girl;glucosuria;hematuria;human;human tissue;hypercalciuria;kidney biopsy;kidney function;kidney injury;kidney tubule acidosis;lupus erythematosus nephritis;major clinical study;male;mesangium;micturition;morphology;nephrosis;prognosis;proteinuria;purpura;side effect;symptom;ultrasound;urinalysis;vasculitis;Wilson disease;endogenous compound;immunoglobulin A;penicillamine,"Wang, X.;Yao, Y.",2016,October,http://dx.doi.org/10.1007/s00467-016-3467-5,0,1,
1271,"An ongoing phase 2, multi-centre, open-label, study of WTX101 in Wilson disease patients - Early observations","Objective: The aim of this ongoing study is to evaluate the efficacy and safety of WTX101 in newly diagnosed Wilson Disease patients. Background: WTX101 (bis-choline tetrathiomolybdate) is an investigational de-coppering agent that is being developed for the treatment of Wilson Disease. The aim of this ongoing study is to evaluate the efficacy and safety of WTX101 in newly diagnosed Wilson Disease patients. Methods: Patients with a confirmed diagnosis of Wilson Disease naive to treatment or treated for <=28 days with chelation or zinc therapy received 30 or 60 mg WTX101 QD during the initiation phase. Dosing was individualized after 6 weeks, guided by laboratory and clinical criteria. Regular assessments included safety, status of liver disease including synthetic function and modified Nazer score, change from baseline in free copper. and neurological status using the Unified Wilson Disease Rating Scale (UWDRS). Results: The first six patients (age 18-53 years; 2 males) were followed for 8 to 36 weeks in the study. Modified Nazer score ranged from 1-5 and 5/6 had neurological manifestations at baseline. Reversible elevated liver function tests related to per-protocol dose escalations was observed in the first 2 patents. After reducing the initiation dose from 30 mg BID (totally 60 mg/day) to 30 mg QD and dose escalation to a maximum daily dose of 60 mg, WTX101 was well tolerated with no SAEs and few AEs. Hepatic status improved or remained stable. Elevated baseline plasma NCC adjusted for molybdenum on average normalized within 3 months. The UWDRS scores improved in all patients with neurological manifestations. By 3 months, the neurological examination score (part III) was reduced from approximately 30 to <10, with continuous improvement thereafter. Daily activity status (part II) showed similar improvement. Conclusions: WTX101 appears safe and well tolerated in patients with Wilson Disease. With improvement in clinical (hepatic and neurologic) and laboratory assessments including copper control in these initial patients, further clinical evaluation is warranted to establish the efficacy and safety of WTX101.",adult;chelation;clinical evaluation;clinical trial;comparative effectiveness;controlled clinical trial;controlled study;daily life activity;diagnosis;drug megadose;female;human;human tissue;liver function test;major clinical study;male;multicenter study;neurologic disease;neurologic examination;normal human;open study;patent;plasma;rating scale;safety;Wilson disease;young adult;choline tetrathiomolybdate;molybdenum;zinc,"Czlonkowska, A.;Weiss, K. H.;Ala, A.;Askari, F.;Nicholl, D.;Schilsky, M. L.",2016,June,http://dx.doi.org/10.1002/mds.26688,0,0,
1272,Iron accumulation in a Wilson disease patient: Longitudinal 7T MRI and transcranial sonography study,"Objective: To investigate longitudinal changes in clinical symptoms, 7T MRI and transcranial sonography (TCS) during chelating treatment in a Wilson disease (WD) patient. Background: Pathophysiological causations and predictive biomarkers of clinical worsening in WD patients on anti-copper treatment are unknown. One of possible contributing factors may be brain iron accumulation. Our goal was to examine longitudinal changes in T2* relaxation time and echogenicity of deep grey matter structures as measures of iron content in a WD patient. Methods: We examined a de-novo WD patient at baseline and followed him periodically for 30 months on anti-copper treatment. Clinical severity was assessed using the Unified Wilson Disease rating scale (UWDRS). The 7T MRI imaging protocol included a 3D magnetization prepared rapid gradient echo (MPRAGE, TE=3 ms; TR=2300 ms) and 2D multi-echo gradient echo (GRE, 8 echoes 4.1-25.5 ms; TR=1820 ms) for T2* parametric mapping. R2* values were measured in the globus pallidus (GP), putamen (Put), caudate nucleus (NC) and thalamus (Thal). TCS was performed and echogenicity indices of lentiform nucleus (NL) and NC were calculated using a software for TCS digital image analysis. Results: 27-year old man developed ataxia and action tremor in hands and was diagnosed with WD (p.H1069Q homozygous mutation) three months later. At baseline there was pronounced NL hyperechogenicity bilaterally; R2* value in the GP (130) was 1.3 times increased compared to four age matched controls (mean 99.9+/-(SD)9.8). After penicillamin treatment initiation (increased to 900mg) ataxia and tremor progressed and generalized dystonia along with vertical gaze palsy appeared. After the switch to trientine (increased to 900mg) and later to Zinc(150mg)+trientine(600mg) his symptoms gradually improved and UWDRS score dropped from 104 to 56. R2* value gradually increased, particularly in Put (red arrows) and Thal (green arrows) suggesting iron accumulation. This was associated with thalamic atrophy and cavitation on MP-RAGE MRI (green arrows). TCS did not show any changes in NL and NC echogenicity during treatment. Conclusions: Our data suggest that increased brain iron concentration may be present already in de-novo WD while further iron deposition may accompany degenerative changes during unsuccessful anticopper treatment. NL hyperechogenicity does not reflect R2* changes and may serve as a trait marker. (Figure Presented).",adult;ataxia;atrophy;case report;caudate nucleus;controlled study;diagnosis;echography;gaze paralysis;generalized dystonia;genetic marker;genetic polymorphism;globus pallidus;gray matter;homozygosity;human;image analysis;male;mutation;nuclear magnetic resonance imaging;putamen;rating scale;relaxation time;software;symptom;thalamus;tremor;Wilson disease;iron;penicillamine;trientine;zinc,"Dusek, P.;Skoloudik, D.;Maskova, J.;Huelnhagen, T.;Bruha, R.;Zahorakova, D.;Niendorf, T.;Ruzicka, E.;Schneider, S. A.;Wuerfel, J.",2016,June,http://dx.doi.org/10.1002/mds.26688,0,0,
1273,Copper chelation efficacy of alginate/chitosan based D-penicillamine nanoparticles in rat model of non-Wilsonian brain copper toxicosis,"Objective: To evaluate the copper (Cu) chelation efficacy of orally administered D-penicillamine loaded nanoparticles to that of conventional D-penicillamine therapy for 90 days in Wistar rat model for non- Wilsonian brain Cu toxicosis. Background: Oral D-penicillamine therapy is unable to attenuate the brain Cu overload and neurological manifestations in Wilsons disease patients. Methods: Atomic absorption spectrophotometry, high performance liquid chromatography, neurobehavioral and histopathological studies, and nanoparticles preparation/physico-chemical characterization were carried out. Results: D-penicillamine nanoparticles exhibited mean 274.09nm size and less than 29.32% of D penicillamine release under in vitro conditions. Pharmacokinetics studies showed augmented levels of Dpenicillamine in brain of nanoparticles based D-penicillamine delivery group compared to conventional Dpenicillamine delivery group. Conventional and nanoparticles based D-penicillamine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary Cu levels in Wistar rat model of copper toxicosis. Conventional D-penicillamine therapy resulted in negative rhodanine staining of brain and liver sections corroborated by 16.4% and 60.1% reduction in brain and hepatic Cu content, respectively compared to non-treated Cu-intoxicated group. However, liver and brain sections of nanoparticles based D-penicillamine therapy group demonstrated grade 1 Cu and no Cu depositions substantiated by 47.2% and 32.8% reduction in hepatic and brain Cu content, respectively in comparison to non-treated Cu-intoxicated group. Conclusions: Our data demonstrates the first in vivo evidence for therapeutic efficacy of D-penicillamine nanoparticles in chelating more brain Cu and mitigating neurological deficits even at half the dose as given in conventional D-penicillamine therapy. (Figure Presented).",animal experiment;animal model;atomic absorption spectrometry;brain;chelation;controlled study;coordination;disease model;drug therapy;high performance liquid chromatography;histopathology;in vitro study;intoxication;liver;memory;nonhuman;pharmacokinetics;physicochemical model;rat;rat model;staining;Wistar rat;alginic acid;chitosan;nanoparticle;penicillamine;rhodanine,"Pal, A.;Thapa, B. R.;Vasishta, R. K.;Prasad, R.",2016,June,http://dx.doi.org/10.1002/mds.26688,0,0,
1274,"Clinical profile of Wilson's disease at Yangon general hospital, Myanmar","Objective: To evaluate clinical, biochemical and imaging profile of patients with Wilson's Disease (WD). Background: There was no reported case series of WD in Myanmar. This study was a hospital -based study carried out at Department of Neurology, Yangon General Hospital, Myanmar. Methods: During the period of 2010 to 2015,17patients were diagnosed with definitive WD and one had likely WD by using Leipzig criteria. Results: Of the18 patients 8 were males and 10 were females. Mean age at the time of diagnosis was 20 years. Main presenting features were: abnormal gait in 17 out of 18 (94.4%); speech problems 17(94.4%), Parkinsonian features 9(50%), tremor 8(44.4%), cerebellar symptoms and signs in 4(22.2%).Fourteen patients (66.6%) had psychiatric symptoms.Five patients (27.7%) had swallowing difficulty, 2(11.1%) had seizures and 1(5.5%) had chorea.KF rings were positive in all patients. Serum ceruloplasmin level was low in 17(94.4%) patients and lower normal limit in one patient.Only 3 patients (16.6%) had coexisting hepatic manifestation.Renal and haematological involvement was seen in 2 patients (11.1%). Three (16.6%) patients had positive family history and one patient (5.5%) had consanguineous marriage of the parents. Only one of the siblings of affected patients was screened and found to have WD. CT (Brain) was done in 8 out of 18 patients (44.4%) and all had bilateral basal ganglia hypodensity and one (5.5%) had subcortical involvement.MRI (Brain) was done in 12 out of 18 patients(61.1%) and showed hyperintense signals inT2 mainly in basal ganglia, thalami and mid brain. All patients were treated with penicillamine initially and zinc as a maintenance therapy.One patient had 12- week pregnancy at the time of diagnosis and penicillamine was given as trientine is not available. Her neurological symptoms markedly improved and but she had premature delivery at 34 weeks. The child was low-birth weight with hypotonia and passed away at one year old.Only 7out of 18 patients (38.8%) came for regular follow- up and clinical improvements were seen but the outcome of eleven patients were not known. Conclusions: The limited access to diagnostic facilities and availability of drugs is a major barrier for the early diagnosis and compliance of long term treatment leading to devastating consequences of the disease in patients in this study.",adult;basal ganglion;cerebellum;ceruloplasmin blood level;child;chorea;clinical trial;consanguineous marriage;controlled study;diagnosis;drug therapy;dysphagia;early diagnosis;family study;female;follow up;gait disorder;general hospital;human;human tissue;infant;low birth weight;maintenance therapy;major clinical study;male;mental disease;mesencephalon;muscle hypotonia;Myanmar;neurology;normal human;nuclear magnetic resonance imaging;parkinsonism;pregnancy;prematurity;seizure;sibling;speech disorder;tremor;Wilson disease;young adult;endogenous compound;penicillamine;trientine;zinc,"Aye, S. M. M.;Kyaw, K. M. P. P.;Myint Shwe, Z.;Ohnmar, O.;Aye, Y. M.;Thit, W. M.",2016,June,http://dx.doi.org/10.1002/mds.26688,0,0,
1275,Clinical and imaging deterioration of a mild case of Wilson's disease after chelation therapy,"Objective: To present a case of a mild wilson disease with neuropsychiatric features which showed clinical and also imaging deteriotation five months after the chelation treatment with trientine. Background: Wilson Disease is a rare autosomal recessive inherited disorder of copper metabolism. Once the diagnosis of Wilsons Disease has been established to our patient proper chelation was initiated ALD from AL the available drugs trientine was choosen. Trientine is a chelator agent indicated as an initial therapy with less adverse effects than penicillamine. Methods: The dosage was initially 300mg daily for the first three months and then 600mg daily in two divided doses for the next two months. as soon as the dosage was increased neurological deterioration has been reported. According the neurological examination enchanced of postural and wing beating tremor had been mentioned as well as gait difficulty with dystonic spasms, mild sensory loss and ataxic speech. The brain MRI was deteriorated in comarison to the previous one obtained before the treatment. A characteristic face of giant panda sign has been described along with lesions in the basal ganglia, thalamus and midbrain. Results: The treatment was discontinued but before the urinary copper excretion was evaluated. After two weeks without treatment patient's clinical condition was improved and urinary copper excertion was reevaluated as well as serum copper both were below of the normal levels. Conclusions: As a conclusion in this case neurological and brain MRI deteriotation was due to excessive copper removal. So tranditional chelating agents may not be safe when used in mild types of wilson disease and preventive therapy like zinc may be more effective and preferable.",Ailuropoda;basal ganglion;case report;chelation therapy;copper blood level;copper metabolism;deterioration;diagnosis;dystonia;excretion;gait;human;human tissue;mesencephalon;muscle spasm;neurologic examination;nonhuman;nuclear magnetic resonance imaging;prophylaxis;sensory dysfunction;speech;thalamus;tremor;Wilson disease;wing;penicillamine;trientine;zinc,"Kleoniki, C.;Spiridon, K.;Cristos, T.;Aristidis, K.",2016,June,http://dx.doi.org/10.1002/mds.26688,0,0,
1276,A case of Wilson's disease presenting with depression as the initial symptom,"Wilson's disease is a chronic disorder resulting from abnormal accumulation of copper in various organs, which is usually accompanied with disorders of metabolism of copper due to specific gene abnormality. Many neurologic symptoms, such as slurred speech, dysarthria, dystonia, parkinsonian feature, chorea and ataxia, are widely known as initial symptoms and syndromes of Wilson's disease. But dementia or frontal lobe syndrome also can be seen in Wilson's disease. Herein we report a case of 17 year old male presenting executive dysfunction and apathy with depressive mood as the initial symptom of Wilson's disease. A 17-year old male derived at our emergency department with apathy which had occurred about 3 days before. His vital signs and lab finding were nonspecific. In initial neurologic examination, executive dysfunctions were suspected. During observation for about 3 h in hospital, he presented mild bilateral action-postural tremor and suspicious slurred speech was noted. In T2-weighted magnetic resonance images, bilateral symmetric high signal intensities in putamen and caudate nucleus. On his past diet history, he had eaten liver of pigs and shellfishes excessively for months, which contents high proportion of copper. Urine copper concentration were elevated (2123.2 lg/24 h) and serum ceruloplasmin level were decreased (< 4 mg/dL). On diagnosis of Wilson's disease, he was treated with zinc and trientine. Wilson's disease can lead to neuropsychiatric symptoms including subcortical dementia and frontal lobe syndrome. Generally, hepatic dysfunction or motor symptoms are frequently noted in early stage of the disease. But, in young age, acute onset of cognition disorders should be considered to Wilson's disease and close observation for neurologic symptoms are needed.",adolescent;animal experiment;animal model;animal tissue;apathy;caudate nucleus;ceruloplasmin blood level;cognitive defect;depression;diagnosis;diet;emergency ward;frontal lobe;liver failure;male;neurologic examination;nonhuman;nuclear magnetic resonance;pig;putamen;shellfish;slurred speech;tremor;urine;vital sign;Wilson disease;trientine;zinc,"Chang, H.;Park, H.;Cheong, J.",2016,August,http://dx.doi.org/10.1111/jnc.13692,0,0,
1277,Wilson's disease associated with immotile cilia syndrome: A case report,"Background and aims: Wilson's disease (WD) and primary ciliary dyskinesia (PCD) are rare autosomalrecessive disorders, both with a frequency <1:15000. We present a unique case of WD associated with PCD. Methods: Case-report Results: A 24-year-old woman was admitted with a history of headache, fatigue, anorexia and weight loss. Liver hardness, hypotonia, hypo-elicitable deep tendon reflexes, slight ataxia and Kayser-Fleischer rings were noted. Lab testing revealed increased liver functioning tests. Patient history highlighted 5 hospital admission for bronchopneumonia before age 12. Each time, lab testing demonstrated increased transaminasemia with normal ceruloplasminemia. Ultrasonography and liver biopsy documented moderate steatosis, at that time interpreted as due to PCD-induced cholestasis. Phase-contrast and electron microscopy revealed ciliary immobility, with no dynein in axoneme: she was diagnosed with PCD. At admission, Fibroscan demonstrated hepatic fibrosis. Brain MRI was unremarkable. Normal ceruloplasminemia, increased cupruria (2260mg/24h, normal<70), fibrosis with high copper liver deposition (349 mg/g; normal<9.9) were found. DNAI1, DNAH5, DNAH11 genes were normal, while compound heterozygosity for 2304-2305insC and R1041W mutations in the ATP7B gene was found, confirming WD. Patient was started on penicillamine, with benefit: 8 years after, she is asymptomatic. Conclusion: WD and PCD coexistence has never been reported. Loci adjacent to ATP7B may contain dyneincodifying sequences, affected by mutations of closer genes. Early diagnosis can save lives. In this case, liver impairment was grossly reverted with de-coppering agents. Moreover, the reduction of ceruloplasmin, being an acute phase reactant, was hindered by recurrent bronchopneumonia due to PCD. Being dogmatic about ceruloplasmin levels can drag away from correct diagnosis and treatment.",case report;ciliary dyskinesia;human;European;neurology;Wilson disease;liver;gene;bronchopneumonia;mutation;weight reduction;hypertransaminasemia;anorexia;heterozygosity;hospital admission;brain;patient;fatigue;medical history;tendon reflex;headache;muscle hypotonia;immobility;hardness;axoneme;elastograph;liver fibrosis;fibrosis;female;electron microscopy;cholestasis;diseases;steatosis;early diagnosis;liver biopsy;diagnosis;echography;nuclear magnetic resonance imaging;ceruloplasmin;penicillamine;dynein adenosine triphosphatase;copper;acute phase protein,"Romoli, M.;Tambasco, N.;Prontera, P.;Nardi, E.;Clerici, C.;Calabresi, P.",2016,June,http://dx.doi.org/10.1111/ene.13094,0,0,
1278,First epidemiologic study of Wilson's disease in France,"Background and aims: In the literature, estimated Wilson disease (WD) prevalence varies between 1/30,000 and 1/100,000. In France, with a population of 64 million inhabitants, one would expect between 640 and 2100 cases of WD. Objectives of this study is to estimate the national prevalence of WD based on data from the French national health insurance information system (SNIIRAM) and to analyse epidemiological data according to age, gender and treatments. Methods: This study concerned all beneficiaries covered by the general health insurance scheme representing 90% of the French population. WD patients were identified on the existence of long term illness eligible for 100% reimbursement of health (affection longue duree (ALD)) with E83.0 code (copper metabolism disorder) or on at least one hospitalization between 2011 and 2013 with the same code. Results: 906 WD patients were identified, that is prevalence of 1.5/100,000. However, it is certainly underestimated because patients stabilized for many years are not registered as ALD. 43.2% were under 40 years old. Almost 40% of the patients were treated by D-Penicillamine and 14.3% by Zinc acetate, 5.6% received neuroleptics, 15% antidepressants. 5.3% had liver transplantation. Triethylenetetramine, delivered as compassionate, doesn't appear in the base. Comparison of these data with the 500 patients followed in the national reference centre for WD will be presented. Conclusion: This is the first French population-based epidemiologic study of WD concerning an exhaustive population, an important step to understand the public health impact of WD and to further study quality of care.",neurology;European;France;epidemiology;Wilson disease;human;patient;population;prevalence;reimbursement;diseases;health insurance;liver transplantation;gender;epidemiological data;information system;hospitalization;national health insurance;metabolic disorder;copper metabolism;health;public health;trientine;neuroleptic agent;zinc acetate;penicillamine;antidepressant agent,"Poujois, A.;Tuppin, P.;Samson, S.;Chaine, P.;Girardot-Tinant, N.;Woimant, F.",2016,June,http://dx.doi.org/10.1111/ene.13093,0,1,
1279,The frequency of copper deficiency due to over-treatment in Wilson's disease patients,"Background and aims: Wilson's disease (WD) is an inherited disorder involving an excess of copper. Lifelong decoppering therapy is needed, but copper deficiency may result and manifest as myelopathy and haematological abnormalities. The aim of the study was to establish the frequency of copper deficiency as a treatment complication in group of WD patients. Methods: We examined consecutive patients who underwent routine follow-up between April 2012 and April 2014. The free serum concentration of copper, full blood counts, and somatosensory evoked potentials (SEPs) to evaluate dorsal column impairment were determined. Careful neurological examination for the presence of clinical signs of myelopathy or neuropathy was done. Overt copper deficiency was defined as the coexistence of low non-bound ceruloplasmin copper (NCC) copper concentration (<5 mug/dl), blood count abnormalities or/and myelopathy detected in SEPs and/or on spinal MRI. Results: 64 patients with WD were enrolled (39% hepatic, 51% neurologic, and 10% presymptomatic features). The calculated NCC was <5mug/dl (normal range, 10 - 15mug/dl) in 14 (21%) patients. In 80% of these patients, SEP conduction times were normal. Copper deficiency was diagnosed in three cases treated with zinc sulphate (two developed myelopathies with haematological signs, one leukopenia). Only one had clinical signs of myelopathy. Conclusion: Overt copper deficiency is a rare (4.6%) adverse effect of long term WD treatment. Neurological signs of copper deficiency are even more rare. However, a low NCC without other clinical signs is common (17%). Regular monitoring of copper metabolism parameters is essential to avoid treatment complications.",human;patient;neurology;European;copper deficiency;Wilson disease;spinal cord disease;blood cell count;follow up;therapy;blood level;spine;evoked somatosensory response;neurologic examination;neuropathy;monitoring;neurologic disease;leukopenia;adverse drug reaction;copper metabolism;metabolism parameters;diseases;nuclear magnetic resonance imaging;copper;ceruloplasmin;zinc sulfate,"Dziezyc, K.;Sobanska, A.;Litwin, T.;Rakowicz, M.;Czlonkowska, A.",2016,June,http://dx.doi.org/10.1111/ene.13092,0,0,
1280,"An ongoing phase-2, open-label study of WTX101 in Wilson disease patients-early observations","Background and aims: WTX101 (bis-choline tetrathiomolybdate) is a de-coppering agent in clinical development for Wilson Disease (WD). The aim of the study is to evaluate the efficacy and safety of WTX101 in WD patients. Methods: Patients naive to treatment or treated for <=28 days with chelation or zinc therapy were initiated on 30 or 60 mg WTX101 daily. Dosing was individualized after 6 weeks, guided by laboratory and clinical criteria. Assessments included safety, hepatic status, copper parameters and neurological status using the Unified Wilson Disease Rating Scale (UWDRS). Results: The first 6 patients were followed for 8 to 36 weeks in the study. Baseline Modified Nazer score ranged from 1-5 and 5/6 had neurological manifestations. Reversible elevated liver function tests after per-protocol dose escalations were observed in the first 2 patents. After reducing the initiation dose from 60 mg to 30 mg daily and dose escalation to a maximum daily dose of 60 mg, WTX101 was well tolerated with no SAEs and few AEs. Hepatic status improved or remained stable. Elevated baseline free copper on average normalized within 3 months. The UWDRS scores and daily activity improved in all neurological patients. Conclusion: WTX101 appears safe and well tolerated in WD patients, with improvement in clinical (hepatic and neurologic) and laboratory assessments. Further clinical evaluation is warranted.",Wilson disease;patient;human;European;neurology;open study;safety;laboratory;patent;liver function test;rating scale;parameters;therapy;chelation;clinical evaluation;copper;choline tetrathiomolybdate;zinc,"Czlonkowska, A.;Weiss, K. H.;Ala, A.;Askari, F.;Nicholl, D.;Schilsky, M.",2016,June,http://dx.doi.org/10.1111/ene.13091,0,0,
1281,Altered zinc ion levels and transporter expression indicate that high liver copper disrupts zinc metabolism in the Atp7b<sup>-/-</sup> mouse model of wilson disease,"Wilson disease is an autosomal recessive disorder caused by a mutation in the ATP7B gene, which encodes for a copper-transporting P-type ATPase. This mutation impacts regulation of copper metabolism primarily in the liver, but in the kidneys and brain as well. Impaired function of the transporter ultimately results in a hyper-accumulation of copper in these organs with subsequent toxicity. While Wilson disease is traditionally viewed as a copper-related disorder, significantly elevated hepatic zinc levels (p <0.01) were observed via inductively-coupled plasma mass spectroscopy in the Atp7b<sup>-/-</sup> mouse model used to study Wilson disease. In order to determine the mechanisms of this observed hepatic hyperzincemia, relative transcription levels of hepatic specific zinc transporters belonging to the ZIP and ZnT families were observed through the use of RT-qPCR. The results obtained showed differences in mRNA levels of zinc transporters in the Atp7b<sup>-/-</sup> mice. Specifically, in 6 week old animals there was an increase in the relative amount of mRNA for the transporters ZIP9 and ZnT10. Further, differences in relative mRNA abundance were observed between 6 week old and greater than 20 week old animals, including decreased expression of ZIP7, ZIP9, ZnT4, ZnT6, and ZnT10 in the greater than 20 week old animals. This suggests there is indeed some connection between transcriptional regulation of hepatic zinc transporters and the abnormal zinc concentrations as a result of elevated hepatic copper levels.",liver;zinc metabolism;mouse;mouse model;Wilson disease;mutation;mass spectrometry;plasma;diseases;toxicity;brain;kidney;copper metabolism;gene;autosomal recessive disorder;copper;zinc ion;messenger RNA;zinc transporter;zinc;copper exporting adenosine triphosphatase,"Meacham, K.;Burkhead, J.",2016,,,0,0,
1282,Developing a copper responsive MRI Contrast Agent,"Copper is the third most abundant trace metal in the body. Normally bound to important biomolecules, copper is an essential redox cofactor in several enzymatic reactions. Disruption of copper homeostasis is associated with a number of diseases including Alzheimer's, Parkinson's, Menkes, and Wilson's disease.1 Local concentrations of copper can vary from a few micromolar to several millimolar in these diseases.2 Early versions of copper responsive MRI agents demonstrated that Zn<sup>2+</sup> interferes with the Cu<sup>2+</sup> response, limiting its use in MR diagnostic applications.3 Here, we report the synthesis and MR properties of a new copper responsive contrast agent for magnetic resonance imaging (MRI). This MR sensor consists of a DO3A gadolinium-based contrast agent where a bis(benzoic-acid)methyl)amine copper-selective recognition motif (L<inf>1</inf>), was introduced. The sensor shows high selectivity to copper ions. Also exhibits high relaxivity (r<inf>1</inf>) with a 42% increase in relaxivity upon binding to 1 equivalent of Cu<sup>2+</sup>. Interestingly, only when fully bound to Cu<sup>2+</sup>, the sensor presents a 610% increase in r1 (~35mM<sup>-1</sup>.s<sup>-1</sup>) in the presence of physiologic concentrations of human serum albumin (HSA), as uniquely reported for high affinity zinc sensors (Figure 1).4 These results demonstrate that it is possible to design a functional MRI contrast agent responsive and selective to copper at low concentrations, paving the way for the possible translation to preclinical imaging. (Figure Presented).",molecular imaging;nuclear magnetic resonance imaging;sensor;nuclear magnetic resonance;diseases;functional magnetic resonance imaging;synthesis;homeostasis;diagnosis;imaging;Wilson disease;copper;contrast medium;gadolinium;trace metal;human serum albumin;benzoic acid;amine;copper ion;zinc,"Paranawithana, N. N.;Martins, A. F.;Zhao, P.;Sherry, A. D.",2016,July,http://dx.doi.org/10.1007/s11307-016-969-2,0,0,
1283,Subclinical neurological involvement does not develop if Wilson's disease is treated early,"Objectives and study: Wilson's disease (WD) is a genetic disorder of copper metabolism in which metal deposits cause dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset. Methods: Thirty-eight WD patients (18 females and 20 males, aged 24.47 +/- 7.50 years), who received an early diagnosis in presymptomatic or mild or moderate liver disease stages without neurological involvement and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were diagnosed in a presymptomatic stage. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation (TMS). Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests. TMS studies were also performed in a separate group of 15 WD patients with neurologic signs (8 males and seven females; mean age 28.2 +/- 12.1 years, mean treatment duration 15.8 +/-9.14 years). Fifteen age-, education-, and sex-matched healthy subjects, not affected by any neurological, psychiatric or other relevant clinical conditions (10 females and five males; mean age 26.7 +/- 9.1 years; years of schooling 13.2 +/- 2. 4) served as the control group for clinical, neurophysiological, neuropsychological and neuropsychiatric evaluation. Results: Patients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3+/-0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement. Conclusion: Early diagnosis and treatment of WD can prevent the onset of neurologic damage, even at subclinical level.",nutrition;gastroenterology;society;European;Wilson disease;human;patient;female;male;early diagnosis;pulse rate;transcranial magnetic stimulation;brain;neurologic disease;behavior disorder;nuclear magnetic resonance;nervous system;nervous system injury;nuclear magnetic resonance imaging;excitability;motor cortex;prognosis;neuropsychological test;leg;liver disease;liver;control group;school;normal human;clinical evaluation;procedures;education;treatment duration;neuroimaging;copper metabolism;genetic disorder;metal;penicillamine;zinc derivative,"Ranucci, G.;Dubbioso, R.;Esposito, M.;Di Dato, F.;Leone, F.;Topa, A.;Quarantelli, M.;Matarazzo, M.;Santoro, L.;Manganelli, F.;Iorio, R.",2016,May,http://dx.doi.org/10.1097/01.mpg.0000484500.48517.e7,0,1,
1284,Autoimmune hepatitis or Wilson's disease or both? Analysis of challenging cases,"Objectives and study: Comorbidity of autoimmune hepatitis (AIH) and Wilson's disease (WD) can be considered, but has never been proven based on therapeutic response. There is a risk of misdiagnosis with standard diagnostic approach. We describe challenging patients where final diagnosis could not be established at primary diagnostic approach and we question coexistence of AIH and WD. Methods: We identified 4 cases among 165 WD (diagnosis according to Ferenci score - FS) and 321 AIH patients, in whom primary diagnosis was changed or questioned. Results: 3 patients were diagnosed because of elevated serum transaminases (TA) activity, and one due to acute hepatic failure. Case 1: diagnosed with AIH based on liver histology (steatohepatitis and fibrosis), ANA 1:640, IgG: 2824,5mg/dl, without WD tests performed. Prednisone and azathioprine (AZT) was not effective and 1 year later diagnosis of WD was done based on results of ceruloplasmin, urine copper excretion, liver copper and molecular test. Penicillamine was introduced, steroids and AZT were withdrawn leading to normal liver tests. Case 2: primarily did not fulfill criteria of WD: ceruloplasmin 16 mg/dl, normal urine copper excretion. Based on ANA 1:640 and ASMA 1:160, liver histology (severe inflammation and fibrosis) prednisolone was started. After 1 year the child developed psychiatric and neurological symptom, brain MRI revealed abnormalities. Based on ceruloplasmin concentration, neurological symptoms and molecular test (1 mutation) WD was diagnosed and zinc therapy was started. Meanwhile the patient was diagnosed with Crohn disease. Patient was treated with zinc, AZT and 5-ASA with good clinical and laboratory response. Case 3: had normal serum ceruloplasmin and urine copper excretion. Based on histology (periportal inflammation), positive ANA 1:320 and ASMA 1:80, prednisolone was initiated. After 1 year TA were still elevated. At 2nd diagnostic approach WD was diagnosed based on ceruloplasmin 14mg/dl and molecular test (FS: 7 points). Penicillamine was initiated and steroids were withdrawn leading to normal liver function tests. Case 4: diagnosed with WD based on ceruloplasmin 16mg/dl, urine copper excretion 4901ug/24h, K-F ring present and molecular test (2 mutations) (FS: 9 points). Penicillamine was started but 1 month later because of hipertransaminasemia and positive ANA (1:40), ASMA (1:40) steroids were added. After next 4 weeks trientine was started and penicillamine withdrawn due to neutropenia. Tapering of steroids led to TA elevation so steroids were continued. Liver biopsy performed after coagulation normalization showed steatohepatitis and fibrosis. Conclusion: WD usually can be distinguished from AIH but in selected cases differential diagnosis is challenging. WD should be retested in patients with poor response to steroids. In a big cohort of WD and AIH patients only one seems to have comorbidity but even in this case AIH was not fully confirmed.",European;autoimmune hepatitis;society;gastroenterology;nutrition;Wilson disease;human;patient;diagnosis;excretion;urine;fibrosis;inflammation;mutation;neurologic disease;comorbidity;liver;liver histology;diagnostic error;treatment response;differential diagnosis;liver biopsy;neutropenia;liver function test;ceruloplasmin blood level;laboratory;acute liver failure;histology;Crohn disease;therapy;brain;child;aminotransferase blood level;risk;nuclear magnetic resonance imaging;steroid;ceruloplasmin;copper;penicillamine;prednisolone;alprazolam;zinc;prednisone;immunoglobulin G;zidovudine;azathioprine;trientine,"Naorniakowska, M.;Wozniak, M.;Pronicki, M.;Kaminska, D.;Janczyk, W.;Dadalski, M.;Socha, P.",2016,May,http://dx.doi.org/10.1097/01.mpg.0000484500.48517.e7,0,0,
1285,Predictors of liver steatosis and fibrosis measured by Fibroscan in children with Wilson's disease,"Objectives and study: Wilson's disease in childhood may present with mild or significant liver injury as indicated by liver biopsy and liver function tests. Zinc or D-penicillamine (D-pen) seem to stop progression of liver damage but zinc effectivity is often questioned. As liver biopsy is not usually repeated in the course of the disease only surrogate markers can be used for assessment of liver disease. Recently non-invasive transient elastography - Fibroscan (Echosens, France) has been applied in many chronic liver diseases for assessment of fibrosis and steatosis. We aimed to evaluate progression of liver disease and response to treatment assessed by Fibroscan in relationship to the extent and type of liver damage before treatment as assessed by liver histology and liver function tests. Methods: We retrospectively analyzed liver histology, liver copper content and biochemical markers of 34 children with Wilson's disease aged 12.8+/-4.1 years at the time of diagnosis and compared them to liver stiffness (LSM) and steatosis (CAP) using Fibroscan after mean period of 9.7yrs of treatment with zinc (n=21) or D-pen (n=13). In addition LSM and CAP results of pts with Wilson's disease were compared to a control group of 20 healthy controls aged 11.8+/-5.3yrs. Liver histology was described semiquantitatively including micro- and macrovesicular steatosis (modified NAFLD scoring system by Kleiner et al.), portal and lobular inflammation and cholestasis. The associations were tested with Spearman R test and differences between groups were tested with Mann-Whitney U test. Results: The selected cohort of patients with Wilson's disease presented with variable fibrosis (grade 3-4 in 13 patients), lobular inflammation (grade 2-3 in 2 pts), portal inflammation (grade 2-3 in 3 pts), microvesicular (grade 2-3 in 3pts) and macrovesicular steatosis (grade 2-3 in 12pts) and without cholestasis. There were no differences in pre-treatment parametres between children treated with Zn and D-pen. Liver fibrosis (LSM) assessed by Fibroscan was slightly but significantly higher in pts with Wilson's disease than in healthy controls [5 (4.1-6.1) vs. 4.2 (3.8-4.5) kPa] and steatosis expressed by CAP was also increased [252 (218-292) vs. 182 (119-194) dB/m]; p<0.05. We found a significant relationship between liver steatosis assessed by Fibroscan (CAP) and macrovesicular liver steatosis on liver biopsy (r=0.68) while LSM was not related to liver fibrosis. LSM significantly correlated with baseline total bilirubin levels (r=0,4) but not with other liver function tests, ceruloplasmin or liver copper content. We found no difference in Fibroscan results between groups treated with D-pen or zinc [LSM 5.4 (4.3-6.1) vs 4.5 (4.1-5.8) kPa; CAP 251 (208-266) vs. 256 (235- 307) dB/m]. Conclusion: Liver steatosis in children with Wilson's disease seems not to respond to treatment and the extent of steatosis in the course of the disease is closely related to pre-treatment values. Fibrosis at start of therapy is affected by treatment and may change significantly with time. D-pen and Zn therapy seem to be equally effective when tested with Fibroscan in children with mild liver injury.",society;human;fatty liver;fibrosis;European;elastograph;child;gastroenterology;nutrition;Wilson disease;steatosis;liver injury;liver histology;liver function test;inflammation;liver biopsy;liver;patient;liver fibrosis;liver disease;cholestasis;therapy;chronic liver disease;France;elastography;disease marker;rank sum test;scoring system;control group;rigidity;diagnosis;childhood;zinc;copper;ceruloplasmin;bilirubin;penicillamine;nitrogen 13;biochemical marker,"Janczyk, W.;Pronicki, M.;Grajkowska, W.;Kaminska, D.;Kmiotek, J.;Naorniakowska, M.;Podlaska, M.;Socha, P.",2016,May,http://dx.doi.org/10.1097/01.mpg.0000484500.48517.e7,0,1,
1286,"Serum Zinc levels discriminate ""indeterminate"" acute liver failure from ""Wilson disease"" acute liver failure","Objectives and study: Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism. Combined clinical and laboratory findings are needed for early diagnosis. There is the hypothesis suggested that low serum Zinc (Zn) is related to phenotypic severity of WD. Indeed, alkaline phosphatase (ALP), a Zn-containing metallo-enzymes that reflects the real Zn deficiency is relatively low in WD patients might support this presumption. However, few studies underscore the role of these biomarkers in WD pathogenesis and severity. Our study was aimed to observe the values of serum Zn and other basic biomarkers in acute liver failure (ALF) of indeterminate cause and WD. Methods: Retrospective data was reviewed from children with WD (n=30) and indeterminate ALF (n=9) at King's college hospital in 2005 - 2015. WD patients were diagnosed by King's protocol and 23 patients were confirmed by genetic analysis. WD is classified into WD-ALF and WD non-ALF. The values of serum Zn, copper, ceruloplasmin(CP) and liver function tests were collected. Results: Our study demonstrates, a significantly lower level of serum Zn and corrected Zn in WD-ALF compare to WD non-ALF and ALF of indeterminate cause. Conclusion: The present study showed that the dramatic aberrance of serum Zn in WD-ALF can discriminate WD-ALF from indeterminate ALF. (Table Presented).",acute liver failure;Wilson disease;gastroenterology;European;society;nutrition;zinc blood level;human;patient;hypothesis;hospital;child;early diagnosis;laboratory;pathogenesis;college;zinc deficiency;genetic analysis;liver function test;copper metabolism;autosomal recessive disorder;zinc;biological marker;alkaline phosphatase;copper;ceruloplasmin;enzyme,"Sintusek, P.;Dhawan, A.",2016,May,http://dx.doi.org/10.1097/01.mpg.0000484500.48517.e7,0,0,
1287,Brain MRI and spectroscopy in the diagnosis of early neurological involvement in wilson's disease in children,"Objectives and study: Wilson's disease is an inherited disorder of cupper metabolism characterized by accumulation of cupper in the liver' brain' kidneys and other tissues resulting in hepatic and neuropsychiatric features. Magnetic resonance imaging (MRI) helps in the diagnosis of neurologic Wilson's disease. The literature regarding MR spectroscopy (MRS) in Wilson's disease is limited. The aim of this work was to evaluate the validity of brain MRI and spectroscopy in early detection of central nervous system abnormalities in children with Wilson's disease. Methods: A case-control study was carried out at the Gastroenterology unit' Pediatric department and the Radiology department' at Zagazig University Hospitals, Zagazig, Egypt between March 2011 and March 2014 after IRB approval. Twenty-six patients with Wilson's disease and 26 healthy volunteers were included. Detailed history taking; complete physical examination including anthropometry' regional examination, full abdominal examination and neurological assessment were done. Routine laboratory investigations included CBC' CRP' ESR, reticulocytic count, complete liver function tests, abdominal ultrasound, Immunoglobulin electrophoresis and kidney function tests. Specific investigations included serum ceruloplasmin level, copper concentration in 24-hour-urine collection, copper concentration in 24 hour-urine collection with D-penicillamine challenge test, autoantibodies panel (ANA, ASMA and ALKMA). Slit lamp examination for Kayser-Fleischer ring and percutaneous liver biopsy looking for consistent liver histology (fatty changes or glycogenated nuclei). MRI and MRS were done for all patients. Results: Eight patients showed abnormal magnetic resonance imaging in the form of bilateral increased signal intensity in the basal ganglia in T1-weighted axial MR images. Compared with control subjects, patients with WD had a highly significant decrease in N-acetyl aspartate, choline and creatine values (p<0.001) and significantly decreased N-acetyl aspartate /choline, N-acetyl aspartate /creatine and choline/creatine ratios (p<0.05) of right basal ganglia. Patients complicated with liver cell failure had a highly significant decrease in N-acetyl aspartate (p<0.001) and Significant decrease of choline, creatine values, N-acetyl aspartate /choline, N-acetyl aspartate /creatine and choline/creatine ratios (p<0.05) than patients without complications Conclusion: MRI abnormalities were detected in eight patients out of 26 (30.7%) while MRS showed decrease of N-acetyl aspartate, Choline, Creatinine, N-acetyl aspartate /choline, N-acetyl aspartate /creatine and choline/creatine in all patients. MRS in patients diagnosed as a Wilson's disease detects early neurological changes even with normal MR imaging.",society;human;child;spectroscopy;European;diagnosis;brain;gastroenterology;nutrition;Wilson disease;nuclear magnetic resonance imaging;patient;urine;examination;basal ganglion;liver biopsy;slit lamp;normal human;provocation test;Egypt;university hospital;radiology department;pediatric ward;case control study;tissues;ceruloplasmin blood level;kidney function test;kidney;electrophoresis;liver;metabolism;nervous system malformation;liver histology;ultrasound;central nervous system;diseases;liver function test;validity;liver cell;laboratory;anthropometry;physical examination;nuclear magnetic resonance spectroscopy;nuclear magnetic resonance;anamnesis;n acetylaspartic acid;choline;creatine;copper;autoantibody;penicillamine;immunoglobulin;creatinine,"Hussein, H.;Elsaadany, H. F.;Elghobashy, A. A.;Abdelrahman, H.;Talaat, M. A.;Zeid, A. F.",2016,May,http://dx.doi.org/10.1097/01.mpg.0000484500.48517.e7,0,0,
1288,Evaluation of exchangeable copper and relative exchangeable copper in ATP7b-/- mice,"Objectives and study: Wilson's disease (WD) is an autosomal recessive disease caused by mutations in the ATP7B gene responsible for a toxic accumulation of copper, mainly in the liver and central nervous system. The diagnosis of WD is based on a combination of clinical and biological findings. Phenotypic heterogeneity may challenge the diagnostic confirmation. Exchangeable copper (CuEXC) and its derived Relative Exchangeable Copper (REC, ratio CuEXC/total serum copper, %) have recently been proposed as reliable diagnostic markers in WD. The aim of our study was to validate these new markers in ATP7B<sup>-/-</sup> mice, an animal model of WD. Methods: ATP7B<sup>-/-</sup> (group a) and wild type mice (WT, group b) were bred and investigated in the same conditions. The animals were classified by subgroup based on age at sacrifice (groupe1a and 1b = 6 weeks, 2a and 2b = 20 weeks, 3a and 3b = 40 weeks, 4a and 4b = 50 weeks). The following plasma data were compared between groups: liver function tests, serum copper (Cu), CuEXC, and REC. Histological analysis of the liver and intrahepatic copper (CuIH) determination were also performed. One group of ATP7B<sup>-/-</sup> mice received a treatment with D-penicillamine from week 40 to sacrifice, at week 50 (Group 5). Results: 141 ATP7B<sup>-/-</sup> mice and 117 WT mice were included in the study. No mice died before the scheduled sacrifice. In the WT groups, histological analysis was constantly normal and the values of Cu, CuIH, and CuEXC remained stable over time. Histological analysis of ATP7B<sup>-/-</sup> mice showed a progressive development of chronic liver injury (group 1a: isolated moderate inflammation (48%), group 4a: inflammatory fibrosis (100%) with cirrhosis (65%)). The Cu, CuIH, and CuEXC varied over time with maximum values at week 20 for CuIH and at week 40 for the CuEXC and Cu. In each subgroup, CuIH and CuEXC were significantly higher in ATP7B<sup>-/-</sup> mice as compared to WT mice (p <0.005). The REC was also significantly higher in ATP7B<sup>-/-</sup> mice (mean, 37.9 vs. 11.2% , p <0.001). A threshold value of 20% for the REC provided diagnostic sensitivity and specificity of 100%, regardless of age, sex, or the use of a treatment (group 4a: 34.9% vs. group 5: 33%). Copper chelator significantly reduced liver fibrosis (p=0.03) and Cu (p=0.028) and decreased the CuIH (p=0.29) and the CuEXC (p=0.175). Conclusion: This study confirms the mouse model ATP7B<sup>-/-</sup> as a reliable animal model of chronic liver disease by copper overload. Relative exchangeable copper is a sensitive and specific diagnostic marker in this model. Further studies are needed to confirm that CuEXC is a good biomarker to monitor the evolution of mouse WD, particularly when copper chelators are used.",European;society;gastroenterology;nutrition;mouse;diagnosis;wild type mouse;animal model;liver;copper blood level;inflammation;liver injury;fibrosis;mutation;gene;model;autosomal recessive disorder;mouse model;liver function test;liver cirrhosis;liver fibrosis;sensitivity and specificity;plasma;chronic liver disease;central nervous system;Wilson disease;copper;marker;chelating agent;penicillamine;biological marker,"Heissat, S.;Bost, M.;Hervieu, V.;Brunet, A. S.;Guillaud, O.;Mintz, E.;Lachaux, A.",2016,May,http://dx.doi.org/10.1097/01.mpg.0000484500.48517.e7,0,0,
1289,Analysis of treatments for wilson disease using patient-specific induced pluripotent stem (IPS) cells derived from urine,"Background and Aims: Wilson disease is a monogenetic disorder of copper (Cu) metabolism, which results from mutations in the ATP7B gene. This provokes a functional impairment of Cu excretion by the liver, followed by excess Cu deposition in organs, mostly in the liver and brain. Patients display clinical heterogeneity ranging from acute or chronic liver failure and/or neurological symptoms. The progression of WD can be partly ameliorated by zinc or chelating agents such as D-penicillamine and trientine. Though these treatments are usually effective, severe side effects have been reported in a significant portion of WD patients. The molecular mechanisms of WD and the response to various treatments have not been fully characterized, since specimens of the WD patients for analyses are rare. Consequently, samples of WD patients are indispensable for examinations of the impact of ATP7B mutations on disease pathogenesis. The aim of the study is to generate a novel in vitro methodology to generate WD patient-specific cells that may not only help to understand pathogenesis, but also drug efficacy. This approach can also be used as a tool to investigate novel compounds as well as new gene correction methods. Methods: Urine of WD patients was processed for isolation of renal epithelial cells, followed by reprogramming into WD-iPS cells using non-integrating episomal vectors. After characterization, WD-iPSCs were differentiated into hepatocyte-like cells, using crucial growth factors for 14 days. iPSC-Heps were characterized by qRT-PCR, flow cytometry and immunocytochemistry before they were treated with novel chelating agents under various Cu conditions. Results: Stable cell colonies emerged upon cultivation of urinederived cells and nucleofection generated iPSCs with pluripotent character. iPSC-Heps were identified with similar morphology and gene expression (e.g. ATP7B) in comparison to primary human hepatocytes. The results revealed a significant decrease of Cu content in WD iPSC-Heps after treatment with the novel chelator as compared to untreated WD iPSC-Heps. Conclusions: Our results indicate that iPSCs derived from urine cells of WD patients can be reprogrammed and differentiated into iPSC-Heps. WD iPSC-Heps will allow the establishment of a patient-specific in vitro platform for evaluating drug efficiency. Thus, this technology seems excellently suited for disease modelling and will allow assessment of novel drugs for improved therapy of WD.",liver;Wilson disease;human;patient;urine;European;pluripotent stem cell;drug efficacy;liver cell;pathogenesis;mutation;gene;in vitro study;technology;model;diseases;cell culture;immunocytochemistry;flow cytometry;neurologic disease;chronic liver failure;epithelium cell;brain;methodology;examination;side effect;morphology;gene expression;excretion;therapy;functional disease;copper metabolism;chelating agent;penicillamine;zinc;growth factor;trientine,"Sauer, V.;Niemietz, C.;Guttmann, S.;Stella, J.;Chandhok, G.;Zischka, H.;Zibert, A.;Schmidt, H. H. J.",2016,April,,0,0,
1290,Retrospective study to assess long-term outcomes of chelator-based treatment with trientine in wilson disease patients withdrawn from therapy with D-penicillamine,"Background and Aims: Wilson Disease is a rare autosomal recessive disorder of impaired hepatic copper excretion caused by mutations in the ATP7B gene, resulting in copper accumulation in various organs, including the liver and the brain. It can be fatal if untreated, with patients dying from liver failure or from complications of progressive neurologic disease. The chelating agent Trientine has been demonstrated to be an effective second-line treatment for hepatic Wilson Disease patients. This study aims to determine the long-term efficacy i.e. clinical course of neurological disease and hepatic disease, effects on copper metabolism, and safety and tolerability of using trientine chelator-based treatments after withdrawal from treatment with D-penicillamine. Methods: This is a non-randomised, multicentre, retrospective investigation in Europe, involving approximately 90 Wilson Disease patients. Inclusion criteria include physician-diagnosed WD patients with a ""Leipzig"" score of >=3, aged between 6 and 90 years who have previously withdrawn from treatment with D-penicillamine, and have thereafter been treated with Trientine for a minimum of 6 months. Withdrawal from D-penicillamine can be due to lack of efficacy, safety, tolerability, or other reasons. Results: Information for three endpoints will be collected. The efficacy endpoint will involve assessment of the clinical course of neurological disease and hepatic disease, and effects on copper metabolism, based on an ""Investigator's score"" and baseline status, and will be performed at 6, 12, 24, 36, and 48 month time points. Collection of treatment emergent severe adverse event data, at the same study time points, will provide evidence towards a safety endpoint. A time to discontinuation endpoint, to assess overall adherence to Trientine treatment, based on discontinuation due to adverse events and/or inadequate response, will also be assessed. Conclusions: Results from this retrospective study will be able to inform on the efficacy and safety of Trientine use in Wilson Disease patients in the real world setting.",liver;human;Wilson disease;patient;therapy;European;retrospective study;safety;neurologic disease;disease course;copper metabolism;liver disease;liver failure;brain;gene;mutation;excretion;physician;Europe;autosomal recessive disorder;trientine;penicillamine;chelating agent;copper,"Weiss, K. H.;Albillos, A.;Bruha, R.;Demelia, L.;Dhawan, A.;Griffiths, W.;Hirschfield, G.;Houwen, R.;Manolaki, N.;Poujois, A.;Ribes, C.;Sturniolo, G. C.;Zuin, M.;Chowdhury, S.;Ferenci, P.",2016,April,,0,0,
1291,Prospective study to assess long-term outcomes of treatment with trientine in wilson disease patients withdrawn from therapy with D-penicillamine,"Background and Aims: Wilson Disease is a rare autosomal recessive disorder caused by mutations in the ATP7B gene encoding a membrane-bound enzyme responsible for copper transport in the liver. Wilson Disease patients suffer from an impaired copper metabolism, leading to copper accumulation in various organs, including the liver and brain. Trientine, a chelating compound, is recommended as a second-line treatment for hepaticWilson Disease patients as it leads to removal of excess copper from the body and as a result, prevents further copper accumulation. This study aims to determine the clinical course of copper stores, neurological and hepatic disease aswell as the quality of life ofWilson Disease patients subsequent to initiation of treatment with trientine and after withdrawal from d-penicillamine treatment. Methods: This is a prospective part of a non-randomised, multicentre investigation, involving approximately 55 Wilson Disease patients. Only patients who have been enrolled in the retrospective part of the study and continue to be on standard of care treatment with trientine have been selected for this part of the study. The length of the prospective trial is 12 months with assessments being performed at baseline (enrolment) and at 6 and 12 months following baseline visit. Physical examination, blood and urine sampling, completion of quality of life questionnaire, completion of the Unified Wilson Disease Rating Scale (UWDRS), liver assessments (including noninvasive fibroscan), neurological status, adverse events and concomitant medications assessments will be performed during the three study visits. Results: The primary endpoint to be evaluated will be the percentage of patients with stable disease after 12 months of treatment with trientine based on the investigators score. Unified Wilson Disease Rating Scale (UWDRS) will be measured at 6 and 12 months and compared to the baseline data. Additionally assessment of serum and urinary parameters of copper metabolism will be made at these time points. Quality of life will also be measured. The time to discontinuation of treatment due to adverse events and/or inadequate response will also be assessed. Conclusions: Complementing the retrospective study, the results from this prospective study will inform on the efficacy and safety of trientine, as well as provide valuable quality of life data in Wilson Disease patients treated with trientine following withdrawal of d-penicillamine.",liver;human;Wilson disease;patient;therapy;European;prospective study;quality of life;copper metabolism;rating scale;brain;safety;retrospective study;serum;drug therapy;gene;elastograph;questionnaire;sampling;mutation;urine;blood;physical examination;health care quality;parameters;liver disease;disease course;autosomal recessive disorder;trientine;penicillamine;copper;chelating agent;membrane enzyme,"Weiss, K. H.;Pfeiffenberger, J.;Stremmel, W.;Estall, R.;Gotthardt, D. N.",2016,April,,0,0,
1292,Liver transplantation in severe neurological forms of wilson disease; the French experience,"Background and Aims: The standard treatment of Wilson disease (WD) is a chelating copper agent or zinc salts. Liver transplantation (LT) is indicated in cases of acute liver failure or advanced cirrhosis. The indication of LT in neurological forms without liver decompensation remains controversial. The aim of this retrospective study is to evaluate the effect of LT in WD with severe neurological symptoms without decompensated liver function. Methods: From 2002 to 2015, fifteen patients (mean age 20.4 [12-41] years) underwent a LT in France for severe neurological complications without neurological improvement despite medical treatment, without acute liver failure. All patients received chelating copper and 3 patients received chelating copper with zinc salts. Three patients had worsened after a temporary cessation of treatment without improvement after a well-conducted treatment. Results: Neurological symptoms were heterogeneous, combining dystonic postures, tremor, chorea and akineto hypertonic syndrome. Mean age at diagnosis of WD was 17.7 [6-39] years and the interval time between worsening and LT was 13 [4-24] months. Mean age at LT was 20.4 [12-41] years. All patients were Child score A at the LT, and the analysis of the native liver confirmed cirrhosis. The mean followup time after LT was 52.5 [2-156] months. Eleven patients (73%, mean age 19 [12-30] years) with a mean follow-up of 56 [2-156] months had a neurological improvement after LT, with a significant gain on the quality of life. In 4 (27%) patients, this improvement continues. The remaining four patients (27%, mean age 24 [15-42] years) had no significant improvement of neurological symptoms and died because of infectious complications, after a mean interval of 13 [2-36] months. Three of the four deceased patients had severe akineto hypertonic syndrome and one a rigid dystonia limiting movements and swallowing. There was no difference between thewaiting time in the group of patients alive and the group of deceased patients (12.5 [3-31] months vs. 13.7 [7-24] months, respectively). Conclusions: Liver transplantation is an effective treatment option in Wilson disease for patients with worsening neurological symptoms despite medical treatment, even in the absence of liver failure. Patients with unfavorable evolution died of severe sepsis. A long history of fixed neurological symptoms could be a pejorative factor.",liver;Wilson disease;European;liver transplantation;human;patient;neurologic disease;acute liver failure;therapy;liver cirrhosis;follow up;diagnosis;chorea;tremor;body posture;child;neurological complication;liver failure;swallowing;dystonia;infectious complication;France;quality of life;liver function;retrospective study;sepsis;decompensated liver cirrhosis;copper;zinc derivative,"Sobesky, R.;Poujois, A.;Brunet, A. S.;Broussolle, E.;Guillaud, O.;Salame, E.;Maillot, F.;Vanlemmens, C.;Hermeziu, B.;Meissner, W.;De Ledinghen, V.;Adam, R.;Cherqui, D.;Castaing, D.;Samuel, D.;Woimant, F.;Vallee, J. C. D.",2016,April,,0,0,
1293,"An ongoing phase 2, multi-centre, open-label, study of WTX101 in newly diagnosed wilson disease patients-early observations","Background and Aims: WTX101 (bis-choline tetrathiomolybdate) is an investigational de-coppering agent that is being developed for the treatment of Wilson Disease. The aim of this ongoing study is to evaluate the efficacy and safety of WTX101 in newly diagnosed Wilson Disease patients aged 18 years and older. Methods: Patients with a confirmed diagnosis of Wilson Disease naive to treatment or treated for <=28 days with chelation or zinc therapy received 30 or 60 mg WTX101 QD during the initiation phase. Dosing was individualised after 6 weeks, guided by laboratory and clinical criteria. Regular assessments included safety, status of liver disease including synthetic function and modified Nazer score, change from baseline in free copper (assessed as non-ceruloplasmin bound copper (NCC) adjusted for molybdenum plasma concentration), additional copper endpoints and neurological status using the Unified Wilson Disease Rating Scale (UWDRS). Results: The first six patients (age 18-53 years; 2 males) were followed for 8-36 weeks in the study. Modified Nazer score ranged from 1 to 5 and 5/6 had neurological manifestations at baseline. Reversible elevated liver function tests related to per-protocol dose escalations was observed in the first 2 patents. After reducing the initiation dose from 30 mg BID (totally 60 mg/day) to 30 mg QD and dose escalation to a maximum daily dose of 60 mg, WTX101 was well tolerated with no SAEs and few AEs. Hepatic status (ALT, INR and bilirubin) and the modified Nazer score improved or remained stable. Elevated baseline plasma NCC adjusted for molybdenum on average normalised within 3 months, with further reductions in NCC in the few patients followed longer on treatment. Other copper measurements (exchangeable copper, total serum copper, 24 hour urinary copper excretion) indicate a similar de-coppering pattern. The UWDRS scores improved in all patients with neurological manifestations. By 3 months, the neurological examination score (part III)was reduced from approximately 30 to <10, with continuous improvement thereafter. Daily activity status (part II) showed similar improvement. Conclusions: WTX101 appears safe and well tolerated in patients with Wilson Disease. With improvement in clinical (hepatic and neurologic) and laboratory assessments including copper control in these initial patients, further clinical evaluation is warranted to establish the efficacy and safety of WTX101 for the treatment of Wilson Disease.",liver;Wilson disease;human;patient;European;open study;safety;laboratory;blood level;liver disease;clinical evaluation;therapy;male;rating scale;liver function test;chelation;plasma;copper blood level;excretion;neurologic examination;patent;diagnosis;international normalized ratio;copper;molybdenum;choline tetrathiomolybdate;ceruloplasmin;zinc;bilirubin,"Weiss, K. H.;Ala, A.;Askari, F.;Bega, D.;Bronstein, J.;Czlonkowska, A.;Ferenci, P.;Nicholl, D.;Schilsky, M.",2016,April,,0,0,
1294,Late-onset wilson disease: A diagnostic dilemma reported,"Aims. This abstract presents a case of late-onset Wilson disease in a patient with biopsy showing non-alcoholic fatty liver disease (NAFLD). Methods. This case report is based on retrospective chart review. Results. This report presents a case of an obese 53 year-old Chinese woman with a history of ulcerative colitis, who was found to have transaminitis during routine blood work. Work up for abnormal liver enzymes revealed negative hepatitis B antigen, undetectable HBV DNA, negative immune markers, but low serum ceruloplasm (<0.08 g/L). She was also found to have elevated cholesterol and triglyceride levels. Abdominal ultrasound showed moderate fatty infiltration of the liver. 24- hour urine copper excretion was done and was found to be elevated (1.69 mumol/d). Given her high urine copper excretion, she was further worked up for Wilson disease. Slit-lamp examination did not show any evidence of Kayser-Fleischer rings. She then underwent a liver biopsy that showed features consistent with moderate steatohepatits suspicious for, but not diagnostic of Wilson disease. Hepatic parenchymal quantification of copper demonstrated a tissue copper dry weight of 4.42 mumol/g, consistent with the diagnosis of Wilson disease. The patient was given a diagnosis of Wilson Disease and non-alcoholic fatty liver disease (NALFD). Subsequent MRI revealed no central nervous system involvement of Wilson disease. The patient was started on penicillamine at 750 mg and further counseled on weight loss strategies. Conclusions. Wilson disease is classically described as a disease of children and young adults. There have been several case reports, however, describing the disease in older adults. The diagnostic features and genetic background of patients with late onset Wilson disease are not different than those with early onset. This case presents a diagnostic dilemma and approach to the diagnosis of Wilson disease in an older patient with a history, physical exam and other findings consistent with NAFLD. The most frequently observed histological abnormality in patients with Wilson disease is steatohepatitis, which is also seen in NAFLD. As the prevalence and detection of NAFLD increases, so too does the clinical suspicion. This case highlights the importance of considering the diagnosis of late-onset Wilson disease in this population, and presents an approach to diagnosis and treatment in such a patient.",Wilson disease;diagnosis;Canadian;gastrointestinal disease;human;patient;urine;nonalcoholic fatty liver;excretion;case report;medical record review;blood;hypertransaminasemia;biopsy;dry weight;weight reduction;young adult;serum;liver biopsy;slit lamp;ulcerative colitis;liver;female;tissues;central nervous system;population;child;prevalence;adult;ultrasound;nuclear magnetic resonance imaging;copper;marker;hepatitis B antigen;penicillamine;liver enzyme;cholesterol;triacylglycerol;dna,"Mitchell, R.;Ko, H.",2016,,http://dx.doi.org/10.1155/2016/4792898,0,0,
1295,Wilson disease: Acute dystonia during treatment with SSRI or SNRI,"Objectives: We present a patient with Wilson's disease who developed partially reversible dystonia during treatment with venlafaxine or sertraline. Methods: A patient with genetically verified Wilson's disease (ATP7B p.Met769fs; p.His1069Gln comp. het.) was followed clinically, examined with serial MRI, 18F-FDG-PET and 123I-FP-CIT-SPECT. The relevant literature was reviewed. Results: A 31-year old man developed anxiety and depression. Treatment with venlafaxine 75mg/d improved the psychiatric symptoms but perioral dystonia occurred within 2 days. During medication with venlafaxine 150mg/d, diplopia, action tremor and weakness were noted. Wilsons' disease was subsequently diagnosed and copper-chelating therapy with trientine-dihydrochloride initiated. Discontinuation of venlafaxine ameliorated the motor symptoms, but they returned after its reinstatement during trientine treatment. Also under medication with sertraline 50mg/d, there was perioral and tongue dystonia, dysarthria, blepharospasm and gait disturbance, which were partially reversible when sertraline was stopped. The patient's anxiety was controlled symptomatically with oxazepam without worsening of extrapyramidal symptoms. MRI showed hyperintensities in the pons, mesencephalon, claustrum and pyramidal tracts. Glucose metabolism and dopamine reuptake capacity were reduced bilaterally in the basal ganglia. Conclusions: Wilson's disease increases the vulnerability to side effects from SSRI and SNRIs. Previously, acute dystonia has been described in a WD patient receiving clomipramine [1]. Both the imbalance of copper metabolism inherent to WD [2] and treatment with SSRIs [3,4] or SNRIs [5] are known causes of dystonia, and we suggest an additive effect when both factors were present simultaneously. The patient described showed imaging abnormalities in the mesencephalon and upper brain stem, suggesting involvement of monoaminergic neurons.",Wilson disease;diseases;dystonia;Parkinson disease;human;patient;anxiety;mesencephalon;drug therapy;therapy;basal ganglion;imaging;monoamine nerve cell;weakness;tremor;glucose metabolism;pyramidal tract;claustrum;diplopia;pons;extrapyramidal symptom;mental disease;gait;nuclear magnetic resonance imaging;blepharospasm;side effect;copper metabolism;brain stem;male;dysarthria;tongue;single photon emission computer tomography;serotonin noradrenalin reuptake inhibitor;serotonin uptake inhibitor;venlafaxine;sertraline;trientine;clomipramine;copper;dopamine;oxazepam;iodine 123;fluorodeoxyglucose f 18,"Wictor, L.;Wictorin, K.;Widner, H.;Puschmann, A.",2016,January,,0,0,
1296,Late onset wilson's disease with central pontine and extrapontine MRI changes,"Objectives: Classic radiological presentation of Wilson's disease (WD) with face of the ""giant panda"" is typically used to distinguish WD from other extrapyramidal disorders. Central pontine myelinolysis like (CPMlike) changes in WD are rarely reported and are distinct from the classic commonly known osmotic demyelination. Although CPM-like changes on MRI in young WD patients are common, there are no published reports of such radiological picture in the exceptional cases of late onset WD. We report on a late onset WD with sequential MRI changes with response to de-coppering therapy. Methods: A 64 year-old male with pulmonary sarcoidosis presented with a two-year history of worsening axial ataxia, postural, kinetic and rest tremors and cognitive decline. His examination was also significant for generalized hyperreflexia, Babinski sign and the presence of Kayser-Fleischer rings. WD diagnosis was confirmed with low ceruloplasmin and with the presence of homozygous mutation in the ATP7B gene. Results: MRI at symptom onset showed diffuse T2/FLAIR hyperintensity in the pons which was contiguous with hyperintensity of the midbrain, as well as focal hyperintensity in left thalamus and generalized cortical atrophy. Following nine months of chelation with trientine, partial resolution of the T2 hyperintensity in the pons was observed, while thalamus hyperintensity became less conspicuous. Conclusions: WD must be considered in all patients that present with hepatic or neurological symptoms without definitive diagnosis, regardless of age. WD and CPM-like radiological changes in older adult WD patients may be under-recognized, but genetic confirmation and clinical exam findings should guide treatment.",diseases;Wilson disease;Parkinson disease;nuclear magnetic resonance imaging;human;patient;pons;diagnosis;thalamus;Babinski reflex;hyperreflexia;atrophy;examination;central pontine myelinolysis;tremor;male;extrapyramidal syndrome;Ailuropoda;mesencephalon;mutation;chelation;therapy;neurologic disease;adult;gene;lung sarcoidosis;demyelination;trientine;ceruloplasmin,"Biller, T.;Fatterpekar, G.;Nirenberg, M.;Brys, M.",2016,January,,0,0,
1297,Zinc and copper in Alzheimer's disease,"In a recent meta-analysis by Ventriglia and colleagues studying the association of zinc levels with Alzheimer's disease (AD), serum zinc has been found significantly decreased in AD patients compared with healthy controls. However, such a finding does not necessarily propose the causal role of low zinc in the pathophysiology of this neurodegenerative disease. On the basis of available evidence, free copper toxicosis may play a causal role in age-related AD, and zinc therapy can be a rational causal treatment. Nevertheless, a randomized controlled clinical trial testing a definite hypothesis is needed before conclusions can be drawn about the value of zinc supplements in the treatment of AD. Copyright © 2015 - IOS Press and the authors. All rights reserved.",Alzheimer's disease;ceruloplasmin;copper;free copper;metallothionein;neurodegeneration;underreporting;Wilson's disease;zinc;Alzheimer disease/et [Etiology];article;astrocyte;human;pathophysiology;priority journal;Wilson disease/et [Etiology];zinc blood level;copper/to [Drug Toxicity],"Avan, A.;Hoogenraad, T. U.",2015,07 May,http://dx.doi.org/10.3233/JAD-150186,0,0,
1298,A young boy with elevated aminotransferases in physical examination - Two novel missense mutations associated with Wilson's disease were found. [Chinese],"A 3-year-old boy had abnormal liver function, which was found in physical examination, for 5 months before admission. He had no symptoms such as anorexia, poor appetite, and jaundice, had normal growth and development, and showed no hepatosplenomegaly. Laboratory examination revealed significantly reduced ceruloplasmin (35 mg/L), as well as negative hepatotropic virus, cytomegalovirus, and Epstein-Barr virus. There were normal muscle enzymes, blood glucose, and blood ammonia and negative liver-specific autoantibodies. The boy had negative K-F ring and normal 24-hour urine copper (0.56 mumol/L). The ATP7B gene testing for the boy, his sister, and their parents detected two novel missense mutations in the boy and his sister, i.e., compound heterozygous mutations in exon 7 (c.2075T>C, p.L692P) and exon 13 (c.3044T>C, p.L1015P), which were inherited from their father and mother, respectively. Wilson's disease was confirmed by genetic diagnosis in the boy and his sister. The boy and his sister were given a low-copper diet. The boy was administered with penicillamine for decoppering and zinc supplement against copper uptake. His sister received zinc supplement alone because no clinical symptoms were observed. The boy showed normal liver function in the reexamination after 3 months of treatment. Copyright © 2015 Chinese Journal Of Contemporary Pediatrics.",Compound heterozygous mutation;Genetic diagnosis;Wilson's disease;aminotransferase blood level;article;case report;ceruloplasmin blood level;child;childhood disease/dt [Drug Therapy];diet supplementation;diet therapy;exon;heterozygosity;human;laboratory test;male;missense mutation;parent;physical examination;preschool child;Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Zhu, Y.;Deng, S. Y.;Wan, C. M.",2015,15 Jul,http://dx.doi.org/10.7499/j.issn.1008-8830.2015.07.020,0,0,
1299,Effective treatment of d-penicillamine induced elastosis perforans serpiginosa with ALA-PDT,"A case of D-penicillamine(DPA) induced elastosis perforans serpiginosa(EPS) in a 32-year-old Chinese man was reported. The presentation lasted two years and was refractory to traditional medical treatment. He was then commenced on 7.6% 5-aminolevulinic acid (ALA) induced photodynamic therapy(PDT) by a LED light of 633 nm at dose levels of 130J/ cm2 for each session with total 3 sessions at one week interval. The patient was tolerated and responded well to this new approach for DPA-induced EPS without any adverse events. The etiology, pathophysiology, natural history, and treatment options for DPA-induced EPS are reviewed, and the authors suggest this method of treatment to be effective and safe for patients of DPA-induced EPS refractory to conventional therapy. Copyright © 2014 Elsevier B.V.",5-Aminolevulinic acid;D-Penicillamine;Elastosis perforans serpiginosa;Photodynamic therapy;adult;adverse drug reaction/dt [Drug Therapy];adverse drug reaction/si [Side Effect];adverse drug reaction/th [Therapy];article;case report;elastic fiber;elastosis/dt [Drug Therapy];elastosis/si [Side Effect];elastosis/th [Therapy];elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/th [Therapy];human;human tissue;liver biopsy;liver cirrhosis;male;medical history;papule;priority journal;skin atrophy;skin biopsy;skin defect;skin pigmentation;skin pruritus;sun exposure;Wilson disease/dt [Drug Therapy];aminolevulinic acid/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tazarotene/dt [Drug Therapy],"Wang, D.;Liang, J.;Xu, J.;Chen, L.",2015,01 Mar,http://dx.doi.org/10.1016/j.pdpdt.2014.11.001,0,0,
1300,The protection conferred by chelation therapy in post-MI diabetics might be replicated by high-dose zinc supplementation,"The recent Trial to Assess Chelation Therapy (TACT) study, enrolling subjects who had previously experienced a myocardial infarction, has provided strong evidence that intravenous chelation therapy can markedly reduce risk for mortality and vascular events in diabetics, whereas no discernible benefit was observed in non-diabetics. It has plausibly been suggested that this reflects a role for transition metal ions - iron or copper - in the genesis of advanced glycation end products, key mediators of diabetic complications that can destabilize plaque. Since phlebotomy therapy fails to prevent vascular events in diabetics, we hypothesize that labile copper may be the chief culprit whose removal by chelation mediated the benefit observed in TACT. If so, strategies less time and labor intensive than chelation therapy might provide comparable benefit. A number of recent studies report that the copper-specific orally-active chelator trientine can reduce risk for range of diabetic complications in rodents; a clinical trial with this agent demonstrated some decrease in left ventricular mass in diabetics with ventricular hypertrophy. However, until this agent becomes less expensive, supplementation with high-dose zinc may represent a more feasible alternative. Zinc opposes the absorption and redox activity of copper via induction of the antioxidant protein metallothionein, which binds copper tightly. A great many studies demonstrate that increased expression of metallothionein decreases risk for tissue damage in diabetic rodents, and in some of these studies metallothionein expression was boosted by supplemental zinc. Zinc supplementation also modestly improves glycemic control in type 2 diabetics, and might reduce risk for diabetes by protecting pancreatic beta cells from oxidative stress. A long term study assessing the impact of supplementing diabetics with high-dose zinc, assessing risk for mortality, vascular events, and diabetic complications, may be warranted. Histidine, which readily forms complexes with copper that possess superoxide dismutase activity, also has potential for alleviating the contribution of loosely bound copper to AGE formation; moreover, in a recent clinical study, supplemental histidine improved insulin sensitivity and exerted anti-inflammatory and antioxidant effects in women with metabolic syndrome. Since ascorbate can reduce labile copper and thereby enhance its pathogenicity, the impact of high-dose ascorbate supplementation on cardiovascular risk in diabetics should receive further study. Copyright © 2015 Elsevier Ltd.",antiinflammatory activity;antioxidant activity;article;cardiovascular mortality;cardiovascular risk;chelation therapy;clinical study;detoxification;diabetic cardiomyopathy;diabetic nephropathy;diabetic neuropathy;diabetic retinopathy;dietary intake;drug megadose;enzyme activity;glycemic control;heart infarction;heart left ventricle mass;human;insulin sensitivity;ischemic heart disease;maintenance therapy;metabolic syndrome X;non insulin dependent diabetes mellitus;nonhuman;oxidative stress;pancreas islet beta cell;pathogenicity;phlebotomy;protein expression;risk reduction;tissue injury;vitamin supplementation;Wilson disease/dt [Drug Therapy];zinc blood level;advanced glycation end product;ascorbic acid;C reactive protein/ec [Endogenous Compound];cadmium;copper;histidine;interleukin 6/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];monocyte chemotactic protein 1/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];thiobarbituric acid reactive substance/ec [Endogenous Compound];trientine;tumor necrosis factor alpha/ec [Endogenous Compound];vascular cell adhesion molecule 1/ec [Endogenous Compound];zinc/dt [Drug Therapy],"McCarty, M. F.;DiNicolantonio, J. J.",2015,01 May,http://dx.doi.org/10.1016/j.mehy.2015.01.038,0,0,
1301,"Chelation therapy in intoxications with mercury, lead and copper","In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively mobilize deposits of mercury as well as of lead into the urine. These drugs can be administered orally and have relatively low toxicity compared to the classical antidote dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper overload, although 2,3-dimercaptosuccinic acid or tetrathiomolybdate may be more suitable alternatives today. In copper-toxicity, a free radical scavenger might be recommended as adjuvant to the chelator therapy. Copyright © 2014 Elsevier GmbH.","Deferoxamine;dmps;dmsa;Heavy metal;Penicillamine;absorption;blood brain barrier;blood level;brain level;chelation therapy;childhood injury;cognitive defect;copper intoxication/dt [Drug Therapy];copper intoxication;drug contraindication;drug efficacy;drug response;drug safety;human;immune complex nephritis;intoxication/dt [Drug Therapy];lead blood level;lead poisoning/dt [Drug Therapy];maintenance therapy;mercurialism/dt [Drug Therapy];mercury blood level;neurotoxicity;nonhuman;occupational exposure;priority journal;randomized controlled trial(topic);review;risk factor;systemic lupus erythematosus;treatment duration;urinary excretion;Wilson disease/dt [Drug Therapy];2,3 dimercapto propanesulphonate/ad [Drug Administration];2,3 dimercapto propanesulphonate/dt [Drug Therapy];2,3 dimercapto propanesulphonate/iv [Intravenous Drug Administration];2,3 dimercapto propanesulphonate/pa [Parenteral Drug Administration];chelating agent/dt [Drug Therapy];chelating agent/iv [Intravenous Drug Administration];copper/to [Drug Toxicity];dimercaprol/ad [Drug Administration];dimercaprol/cm [Drug Comparison];dimercaprol/dt [Drug Therapy];dimercaprol/po [Oral Drug Administration];dimercaprol/pa [Parenteral Drug Administration];lead/to [Drug Toxicity];mercury/to [Drug Toxicity];penicillamine/dt [Drug Therapy];succimer/ct [Clinical Trial];succimer/cm [Drug Comparison];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];unclassified drug","Cao, Y.;Skaug, M. A.;Andersen, O.;Aaseth, J.",2015,,http://dx.doi.org/10.1016/j.jtemb.2014.04.010,0,0,
1302,A neuropsychological comparison of siblings with neurological versus hepatic symptoms of Wilson's Disease,"Wilson's Disease (WD) (also known as hepatolenticular degeneration) is a rare inherited autosomal recessive disorder of abnormal copper metabolism, with an estimated prevalence of approximately 1 in 30,000. The clinical features associated with WD are highly varied. However, subtypes generally reflect neurological, hepatic, and psychiatric symptoms. The present case study reports two brothers with a recent diagnosis of WD. Neurological symptoms and cognitive deficits were exhibited in one brother (BL) in the form of extrapyramidal features, while the other brother (AL) only exhibited hepatic symptoms. Extensive neuropsychological testing was conducted on both siblings to compare cognitive profiles. Results for BL indicated significantly impaired motor functioning and information processing speed, which impacted him significantly at school. Aspects of executive dysfunction were also apparent in addition to reduced visual and verbal memory, working memory, and attention. Results for AL revealed evidence of verbal memory difficulties and aspects of executive dysfunction. Comparison is made of the distinct and common cognitive characteristics of the cases presented in terms of implications for early intervention and management of cognitive difficulties. Copyright © 2014, © 2014 Taylor & Francis.",cognition;hepatic;hepatolenticular degeneration;neurological;neuropsychological;Wilson's disease;adolescent;adult;alanine aminotransferase blood level;alkaline phosphatase blood level;article;aspartate aminotransferase blood level;Beck Depression Inventory;bradykinesia;brain injury;case report;cognitive defect;controlled oral word association test;copper blood level;dysarthria;dysphagia;dystonia;face asymmetry;factorial analysis;human;hypersalivation;leg injury;liver function test;male;mood disorder;neuropsychological test;psychologic test;Rey auditory verbal learning test;speech disorder;symbol digit modalities test;traffic accident;tremor;urinalysis;verbal memory;vomiting;Wechsler intelligence scale;Wechsler memory scale;Wilson disease/di [Diagnosis];copper;penicillamine,"Arguedas, D.;Stewart, J.;Hodgkinson, S.;Batchelor, J.",2015,04 Mar,http://dx.doi.org/10.1080/13554794.2013.878726,0,0,
1303,Editorial,,acute liver failure/di [Diagnosis];adult;blood analysis;case report;cephalopelvic disproportion/di [Diagnosis];cesarean section;echography;edema/di [Diagnosis];editorial;family history;female;HELLP syndrome;human;liver biopsy;liver cirrhosis;liver graft;lung infiltrate;pelvic examination;preeclampsia;proteinuria/di [Diagnosis];puerperium;swelling;urinalysis;Wilson disease/di [Diagnosis];young adult;albumin;copper/ec [Endogenous Compound];diuretic agent;furosemide;penicillamine;spironolactone;zinc/po [Oral Drug Administration],"Caliskan, E.",2015,,,0,0,
1304,Unilateral rubral tremors in Wilson's disease treated with dimercaprol,"Tremors are reported as the most frequent neurological manifestation of Wilson's disease (WD) in some series. Postural tremors, rest tremors, action tremors and wing-beating (rubral) tremors are the different types of tremors seen in WD. We report a patient of WD with unilateral rubral tremors refractory to 1-year therapy with Penicillamine and anti-tremor medications. The tremors decreased considerably after adding chelation therapy with dimercaprol. Combination of Penicillamine and dimercaprol is an effective decoppering measure in rubral tremors of WD.",bal;chelation;dimercaprol;rubral tremors;Wilson's disease;adult;article;bolus injection;case report;ceruloplasmin blood level;chelation therapy;clinical effectiveness;clinical examination;disease severity;drug dose increase;drug efficacy;follow up;general condition improvement;human;male;medical history;medication compliance;neuroimaging;nuclear magnetic resonance imaging;outcome assessment;patient compliance;tremor/dt [Drug Therapy];unilateral rubral tremor/dt [Drug Therapy];unilateral rubral tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;clonazepam/dt [Drug Therapy];dimercaprol/cb [Drug Combination];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];primidone/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc/dt [Drug Therapy],"Chakor, R.;Bharote, H.;Eklare, N.;Tamboli, K.",2015,01 Jan,http://dx.doi.org/10.4103/0972-2327.144286,0,0,
1305,Wilson's disease,"Wilson's disease, is a rare progressive genetic disorder of copper metabolism associated with hepatolenticular degeneration. Left untreated, it invariably results in severe disability and death. The diagnosis is very easily overlooked but if discovered early, effective treatments are available that will prevent or reverse many manifestations of this disorder. The role of copper in disease pathogenesis, coupled with clinical, biochemical, and genetic markers, are pivotal to establishing a clear diagnosis. Medical therapy involves several chelating agents (e.g. penicillamine, trientine) and zinc salts. Liver transplantation corrects the underlying pathophysiology and can be lifesaving. Knowledge of the Wilson's disease gene has opened up a new molecular diagnostic repertoire in the investigation of a suspected patient and first-degree relatives. Copyright © 2015 Elsevier Ltd.",caeruloplasmin;copper;hepatotoxicity;Kayser-Fleischer rings;liver failure;penicillamine;tremor;trientine;Wilson's disease;zinc;article;copper metabolism;deterioration;diet;disability;disease course;eye disease;first degree relative;genetic marker;human;liver disease;liver transplantation;mental disease;molecular diagnosis;neurologic disease;pathogenesis;pathophysiology;priority journal;prognosis;urinary excretion;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Ala, A.",2015,November,http://dx.doi.org/10.1016/j.mpmed.2015.08.011,0,0,
1306,Treatment of Wilson's disease - Another point of view,,Anticopper treatment;Copper;D-penicillamine;Neurological deterioration;Wilson's disease;Zinc sulfate;abdominal pain/si [Side Effect];ageusia/si [Side Effect];albuminuria/si [Side Effect];bone marrow depression/si [Side Effect];brain injury;copper metabolism;editorial;elastosis perforans serpiginosa/si [Side Effect];gastritis/si [Side Effect];Goodpasture syndrome/si [Side Effect];human;immune deficiency/si [Side Effect];leukopenia/si [Side Effect];lupus like syndrome/si [Side Effect];myasthenia/si [Side Effect];neurologic disease;neurological complication;pancreatitis/si [Side Effect];patient compliance;perforating/si [Side Effect];priority journal;proteinuria/si [Side Effect];rash/si [Side Effect];side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];skin disease/si [Side Effect];stomach pain/si [Side Effect];thrombocytopenia/si [Side Effect];treatment outcome;urinary excretion;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];pancreas enzyme/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy],"Czlonkowska, A.;Litwin, T.",2015,01 Mar,http://dx.doi.org/10.1517/21678707.2015.1016907,0,0,
1307,Small fiber peripheral neuropathy in wilson disease: An in vivo documentation by corneal confocal microscopy,"PURPOSE. Wilson disease (WD) is a disorder of hepatic copper metabolism leading to copperaccumulation in hepatocytes and in extrahepatic organs, as the brain and cornea. The aim of this study was to investigate central corneal changes and in particular to assess the parameters of corneal subbasal nerve plexus (SBNP) in patients affected by WD, using corneal confocal microscopy (CCM). METHODS. A total of 24 patients affected by WD and 24 healthy control subjects were included in this cross-sectional comparative study. One eye of each subject was examined to quantify different corneal parameters. Mean cell diameter and mean cell density of the epithelium; number of fibers (NF), nerve fiber length density (NFLD), number of branchings (NBr), number of beadings (NBe), and fiber tortuosity (FT) of the SBNP; mean cell density of keratocytes of the anterior, medium, and posterior stroma; and mean cell density, polimegatism, and pleomorphism of the endothelium, and central corneal sensitivity were analyzed. RESULTS. Wilson disease induced significant alterations in SBNP, and corneal epithelium. The NFLD (P < 0.0001), NF (P < 0.001), NBe (P < 0.025), and NBr (P < 0.0001) were significantly lower, whereas FT (P < 0.0001) was significantly higher in WD subjects compared to controls. Moreover mean epithelial cell diameter (P < 0.0001) and mean epithelial cell density (P < 0.0001) were significantly higher and lower compared to controls, respectively. CONCLUSIONS. The CCM showed significant corneal changes in SBNP, with concomitant corneal epithelium changes in WD, demonstrating the presence of small fiber peripheral neuropathy in these patients. The CCM may contribute to diagnosis and monitoring of the peripheral nervous system involvement in WD. Copyright © 2015, The Association for Research in Vision and Ophthalmology, Inc.All rights reserved.",Corneal confocal microscopy;Subbasal nerve plexus;Wilson disease;adult;article;cell density;clinical article;comparative study;confocal microscopy;controlled study;cornea epithelium;cornea sensibility;corneal parameters;corneal subbasal nerve plexus;cross-sectional study;female;fiber tortuosity;human;image analysis;male;nerve fiber;nerve fiber length density;nerve plexus;number of beading;number of branchings;number of fiber;peripheral neuropathy;priority journal;visual system parameters;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy],"Sturniolo, G. C.;Lazzarini, D.;Bartolo, O.;Berton, M.;Leonardi, A.;Fregona, I. A.;Parrozzani, R.;Midena, E.",2015,,http://dx.doi.org/10.1167/iovs.14-15004,0,0,
1308,Adult liver disorders caused by inborn errors of metabolism: Review and update,"Inborn errors of metabolism (IEMs) are a group of genetic diseases that have protean clinical manifestations and can involve several organ systems. The age of onset is highly variable but IEMs afflict mostly the pediatric population. However, in the past decades, the advancement in management and new therapeutic approaches have led to the improvement in IEM patient care. As a result, many patients with IEMs are surviving into adulthood and developing their own set of complications. In addition, some IEMs will present in adulthood. It is important for internists to have the knowledge and be familiar with these conditions because it is predicted that more and more adult patients with IEMs will need continuity of care in the near future. The review will focus on Wilson disease, alpha-1 antitrypsin deficiency, citrin deficiency, and HFE-associated hemochromatosis which are typically found in the adult population. Clinical manifestations and pathophysiology, particularly those that relate to hepatic disease as well as diagnosis and management will be discussed in detail. Copyright © 2014 Elsevier Inc.",Alpha-1 antitrypsin deficiency;Citrin deficiency;HFE-associated hemochromatosis;Inborn errors of metabolism;Wilson disease;adult;adult disease/co [Complication];adulthood;alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/dt [Drug Therapy];alpha 1 antitrypsin deficiency/et [Etiology];autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/et [Etiology];autosomal recessive disorder/su [Surgery];citrin deficiency/di [Diagnosis];citrin deficiency/et [Etiology];citrin deficiency/su [Surgery];citrullinemia type II/di [Diagnosis];citrullinemia type II/et [Etiology];clinical feature;diet supplementation;hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];hemochromatosis/su [Surgery];human;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/et [Etiology];inborn error of metabolism/su [Surgery];liver disease/co [Complication];liver transplantation;low carbohydrate diet;molecular genetics;molecular pathology;nonhuman;phlebotomy;protein diet;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];4 phenylbutyric acid/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy],"Chanprasert, S.;Scaglia, F.",2015,01 Jan,http://dx.doi.org/10.1016/j.ymgme.2014.10.011,0,0,
1309,Wilson's disease masked by glucose-6-phosphate dehydrogenase deficiency - A case report,"Wilson's disease usually presents with hepatic or neurological manifestations. Hemolysis is an unusual presentation. We describe a case of a young man who had multiple attacks of hemolysis, diagnosed as glucose- 6-rhohosrhohate dehydrogenase (G-6-P D) deficiency, and followed many years later by hepatic manifestations eventually diagnosed as Wilson's disease. Copyright © 2015, Kuwait Medical Association. All rights reserved.",Hemolytic anemia;Hepatic dysfunction;adult;anisopoikilocytosis;article;ascites;blood transfusion;case report;consciousness level;drowsiness;echography;family history;fatigue;flapping tremor;glucose 6 phosphate dehydrogenase deficiency/th [Therapy];hematologic disease;hemoglobin blood level;hepatic encephalopathy;hepatosplenomegaly;human;hyperpigmentation;immunosuppressive treatment;international normalized ratio;Iranian (citizen);iron overload/dt [Drug Therapy];jaundice;laboratory diagnosis;leg edema;Leipzig score;liver biopsy;liver function test;liver hemosiderosis;liver level;liver transplantation;male;normochromic normocytic anemia;partial thromboplastin time;physical examination;scoring system;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper;deferoxamine mesylate/dt [Drug Therapy];glucose 6 phosphate dehydrogenase/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Abdelshahid, M. M. S.;Youssef, M. Y. Z.;Alqallaf, A.",2015,01 Sep,,0,0,
1310,Neural plasticity and memory: Molecular mechanism,"Deciphering the cellular and molecular mechanisms of memory has been an important topic encompassing the learning and memory domain besides the neurodegenerative disorders. Synapses accumulate cognitive information from life-lasting alterations of their molecular and structural composition. Current memory storage models identify posttranslational modification imperative for short-term information storage and mRNA translation for long-term information storage. However, the precise account of these modifications has not been summarized at the individual synapse level. Therefore, herein we describe the spatiotemporal reorganization of synaptic plasticity at the dendritic spine level to elucidate the mechanism through which synaptic substructures are remodeled; though at the molecular level, such mechanisms are still quite unclear. It has thus been concluded that the existing mechanisms do not entirely elaborate memory storage processes. Further efforts are therefore encouraged to delineate the mechanism of neuronal connectivity at the chemical level as well, including inter- or intramolecular bonding patterns at the synaptic level, which may be a permissive and vital step of memory storage. Copyright © 2015 by De Gruyter.",learning;long-term potentiation;memory encoding;synapse;synaptic plasticity;actin polymerization;action potential;Alzheimer disease;amnesia;amygdaloid nucleus;article;autism;autophosphorylation;brain nerve cell;calcium transport;cerebellum;chelation;coated vesicle;conditioning;corpus striatum;declarative memory;dendrite;dendritic spine;DNA modification;Down syndrome;electrical synapse;endocytosis;explicit memory;extracellular matrix;glutamatergic synapse;hippocampus;homeostasis;honeybee;human;hyperpolarization;immediate early gene;implicit memory;intracellular transport;long term depression;long term potentiation;medial temporal lobe;memory;memory consolidation;myelination;myristylation;nerve cell membrane steady potential;nerve cell plasticity;nerve conduction;nerve fiber;nerve fiber growth;neurologic disease;neuropil;neurotransmission;neurotransmitter release;nonhuman;palmitoylation;postsynaptic density;postsynaptic membrane;priority journal;protein acetylation;protein glycosylation;protein phosphorylation;protein processing;protein synthesis;RNA translation;short term memory;spatial memory;synapse vesicle;synaptic membrane;synaptic transmission;synaptosome;transmission electron microscopy;Wilson disease;working memory;4 aminobutyric acid/ec [Endogenous Compound];acetylsalicylic acid;adenylate cyclase/ec [Endogenous Compound];AMPA receptor/ec [Endogenous Compound];amyloid beta protein/ec [Endogenous Compound];brain derived neurotrophic factor receptor/ec [Endogenous Compound];calcium calmodulin dependent protein kinase II/ec [Endogenous Compound];calcium ion/ec [Endogenous Compound];cyclic AMP dependent protein kinase/ec [Endogenous Compound];cyclic AMP responsive element binding protein/ec [Endogenous Compound];cytoskeleton protein/ec [Endogenous Compound];deferoxamine;edetic acid;endocannabinoid/ec [Endogenous Compound];genomic DNA/ec [Endogenous Compound];glutamic acid/ec [Endogenous Compound];metabotropic receptor/ec [Endogenous Compound];metal;metal ion/ec [Endogenous Compound];mitogen activated protein kinase/ec [Endogenous Compound];n methyl dextro aspartic acid receptor/ec [Endogenous Compound];neurotransmitter/ec [Endogenous Compound];neurotransmitter receptor/ec [Endogenous Compound];neurotransmitter transporter/ec [Endogenous Compound];nitric oxide/ec [Endogenous Compound];penicillamine;postsynaptic receptor/ec [Endogenous Compound];protein kinase C/ec [Endogenous Compound];scaffold protein/ec [Endogenous Compound];synaptophysin/ec [Endogenous Compound],"Amtul, Z.;Atta Ur, Rahman",2015,01 Jun,http://dx.doi.org/10.1515/revneuro-2014-0075,0,0,
1311,Hemolytic anemia as first presentation of wilson's disease with uncommon ATP7B mutation,"Wilson's disease (WD) is a rare inherited disorder of copper metabolism and the main manifestations are liver and brain disorders. Hemolytic anemia is an unusual complication of WD. We describe a 15-year-old girl who developed hemolytic anemia as the first manifestation of Wilson's disease. An Arg952Lys mutation was found in exon 12 of the ATP7B gene, which is uncommon among Chinese Han individuals. From this case and reviews, we can achieve a better understanding of WD. Besides, we may conclude that the probable diagnosis of WD should be considered in young patients with unexplained hemolytic anemia, especially in patients with hepatic and/or neurologic disorder. Copyright © 2015, Int J Clin Exp Med. All Rights Reserved.",atp7b;Hemolytic anemia;Wilson's disease;adolescent;alertness;article;ascites;case report;cornea disease;delirium;drug dose reduction;dysarthria;edema;fatigue;female;gene mutation;hemolytic anemia/co [Complication];hemolytic anemia/di [Diagnosis];hemolytic anemia/dt [Drug Therapy];human;kayser fleischer ring;physical examination;protein expression;reticulocyte count;scoring system;splenomegaly;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];arginine/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];CD59 antigen/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];decay accelerating factor/ec [Endogenous Compound];dexamethasone/dt [Drug Therapy];diuretic agent;lysine/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];prednisone/po [Oral Drug Administration];urobilinogen/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound],"Ye, X. N.;Mao, L. P.;Lou, Y. J.;Tong, H. Y.",2015,,,0,0,
1312,Pregnancy and delivery in women with esophageal varices due to hepatic vein thrombosis,"Aim: Retrospective analysis of the course of pregnancy, labor and mode of anesthesia in women with portal hypertension and esophageal varices induced by portal vein thrombosis. Material: From 2000 to 2012 seven pregnant were admitted. None had liver transplantation (Ltx), the varicose have been in the 1st stage. Each of them has been consulted by the obstetrician, transplant surgeon and anesthetist. The patient condition during pregnancy, labor and postpartum period was analyzed. Results: Pregnancy in five cases proceeded physiologically. In one threatening miscarriage was diagnosed and treated with gestagens, two patients had tocolytic. One required variceal banding twice. In three thrombocytopenia worsened, with platelet count <70g/L (up to 59g/L). They received platelet transfusion before delivery. In one case, significant hipoproteinemia (4.7g/L) occurred. In a case, GDM G1 and oligohydramnios were found. All women delivered at term (37-40Hbd). In all general anesthesia with the use of remifentanil was done. There were no fluctuations in MAP and HR. Incision to delivery time was 2.5min. Time from opioid administration to birth was <4min. All children were born in good condition, weight 10-90 percentile. Regional anesthesia is contraindicated in patients with thrombocytopenia. In patients with esophageal varices sudden increase in heart rate and blood pressure can cause hemorrhage. Conclusion: Patients with portal hypertension can deliver at term. It is a high-risk pregnancy. In this group it is desirable to shorten the second stage of labor or complete it by c-section under general anesthesia with remifentanyl which allows getting desired analgesia without complications in the newborn. Surveillance of pregnant with portal hypertension must include monitoring of liver function and coagulation disorders. Copyright © 2014 Informa UK Ltd. All rights reserved.",Delivery;Hepatic vein thrombosis;Remifentanyl;Varicose veins;anemia/di [Diagnosis];anemia/dt [Drug Therapy];article;birth weight;Budd Chiari syndrome/co [Complication];clinical article;disease exacerbation;esophagus varices/co [Complication];female;gastroenterological procedure;general anesthesia;heart rate;human;hypoproteinemia/di [Diagnosis];infant;liver vein thrombosis/dt [Drug Therapy];mean arterial pressure;newborn;oligohydramnios/di [Diagnosis];polycythemia vera;portal hypertension/co [Complication];pregnancy diabetes mellitus/di [Diagnosis];pregnancy outcome;regional anesthesia;retrospective study;spontaneous abortion/dt [Drug Therapy];thrombocyte count;thrombocyte transfusion;thrombocytopenia/co [Complication];thrombocytopenia/di [Diagnosis];thrombocytopenia/th [Therapy];thrombophlebitis/dt [Drug Therapy];variceal banding;Wilson disease/dt [Drug Therapy];gestagen/dt [Drug Therapy];iron/dt [Drug Therapy];iron/po [Oral Drug Administration];low molecular weight heparin/dt [Drug Therapy];opiate;remifentanil;uterus spasmolytic agent/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Jabiry-Zieniewicz, Z.;Dabrowski, F. A.;Suchonska, B.;Kowalczyk, R.;Nowacka, E.;Kociszewska-Najman, B.;Pietrzak, B.;Malkowski, P.;Wielgos, M.",2015,01 Jan,http://dx.doi.org/10.3109/14767058.2014.908846,0,0,
1313,Isolated lingual involvement in Wilson's disease,"Lingual involvement can occur in a variety of neurological disorders including pyramidal, extrapyramidal and lower motor neuron disorders. It can be seen in the form of tremor, bradykinesia, dystonia, atrophy and weakness of tongue movements and can clinically present as difficulty in swallowing and dysarthria which can be a source of great discomfort to the patient. We describe a patient who presented with isolated lingual involvement and was diagnosed to have Wilsons's disease. This case emphasizes the clinical variability in presentation of Wilson's disease and importance of early clinical diagnosis.",Bradykinesia;lingual involvement;Wilson's disease;adolescent;article;brain region;case report;caudate nucleus;ceruloplasmin blood level;copper metabolism;human;leukopenia;liver cirrhosis;male;medical history;mesencephalon;muscle rigidity;Myerson sign;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;pons;portal hypertension;priority journal;putamen;speech disorder;splenomegaly;thalamus;tongue disease/co [Complication];tongue disease/di [Diagnosis];tongue disease/dt [Drug Therapy];tongue disease/et [Etiology];tongue paralysis;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Choudhary, N.;Joshi, L.;Duggal, A.;Puri, V.;Khwaja, G. A.",2015,01 Jul,http://dx.doi.org/10.4103/0976-3147.154578,0,0,
1314,Catatonia: An unusual manifestation of wilson's disease,"Wilson's disease, characterized by abnormal copper accumulation in the human body, may present with psychiatric manifestations in about one-fifth of patients. The authors report a patient with Wilson's disease who initially presented with acute psychosis and later developed catatonic symptoms. The atypical presentation led to a delay in diagnosis and institution of appropriate treatment. Wilson's disease can be ruled out in all young patients presenting with psychiatric symptoms for the first time by screening for a Kayser-Fleischer ring. Copyright © 2015, J Neuropsychiatry Clin Neurosci. All rights reserved.",acute psychosis;adult;article;case report;catatonia rating scale;catatonic schizophrenia/di [Diagnosis];catatonic schizophrenia/dt [Drug Therapy];ceruloplasmin blood level;daily life activity;differential diagnosis;extrapyramidal symptom;female;fever;human;neurologic examination;priority journal;psychomotor retardation;psychosocial withdrawal;rating scale;rigidity;scoring system;slowness;speech disorder;suspiciousness;ultrasound;Wilson disease/dt [Drug Therapy];young adult;aripiprazole/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;lorazepam/dt [Drug Therapy];lorazepam/iv [Intravenous Drug Administration];lorazepam/vi [Intravitreal Drug Administration];lorazepam/po [Oral Drug Administration];olanzapine/cb [Drug Combination];olanzapine/dt [Drug Therapy];penicillamine/cb [Drug Combination];pyridoxine/cb [Drug Combination];pyridoxine/po [Oral Drug Administration];quetiapine/dt [Drug Therapy];risperidone/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Basu, A.;Thanapal, S.;Sood, M.;Khandelwal, S. K.",2015,,http://dx.doi.org/10.1176/appi.neuropsych.13120362,0,0,
1315,"Comment on ""New antioxidant drugs for neonatal brain injury""",,Alzheimer disease;bilirubin blood level;blood flow;brain injury;brain ischemia;cell survival;central nervous system;chelation therapy;drug mechanism;drug metabolism;follow up;gene expression;human;Huntington chorea;hyperbilirubinemia;immune response;knowledge base;learning;letter;lipid peroxidation;long term care;membrane;memory;neurologic disease;neuroprotection;neurotransmitter release;newborn;newborn disease;newborn period;oxidation;oxidative stress;oxygen toxicity;parkinsonism;primary prevention;retrolental fibroplasia;Wilson disease;antioxidant;bilirubin/ec [Endogenous Compound];catalase/ec [Endogenous Compound];cytochrome P450/ec [Endogenous Compound];disulfide;free radical;hemoprotein/ec [Endogenous Compound];neuroprotective agent;nitric oxide/ec [Endogenous Compound];nonmetal;oxygen derivative;penicillamine;peroxidase,"Lakatos, L.;Balla, G.",2015,,http://dx.doi.org/10.1155/2015/384372,0,0,
1316,No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long-term follow-up,"Background and Aims: Data on risk of hepatocellular carcinoma (HCC) in patients with Wilson disease are scarce. We determine HCC risk in a well-defined cohort of Wilson patients. Methods: All patients with a confirmed diagnosis of Wilson disease (Leipzig score>=4) in three Dutch university referral hospitals were included in this retrospective cohort study. End of follow-up was defined as date of diagnosis of HCC, liver transplantation, death, or last available hospital visit. Also, a meta-analysis was performed to determine incidence and mortality rate of HCC in Wilson disease based on all published cohorts. Results: In total, 130 patients with Wilson disease were followed during a median follow-up of 15 years (range 0.1-51.2). At baseline, cirrhosis was present in 74 patients (57% of total: 64% compensated, and 36% decompensated). At end of follow-up, liver disease severity was improved, stable or deteriorated in 20%, 46%, and 24% of all cases (10% unknown), respectively. Two patients developed HCC (one despite excellent decoppering after 50 years follow-up, the other with newly diagnosed Wilson disease). Estimated annual HCC risk for all patients was 0.09% (95% confidence interval [CI]: 0.01-0.28). Subgroup analysis in cirrhotic patients revealed an annual HCC risk of 0.14% (95% CI: 0.02-0.46). The meta-analysis showed an annual HCC risk of 0.04% (95% CI: 0.01-0.10) and HCC mortality rate of 2.6/10000 person-years (95% CI: 0.7-7.0). Conclusions: Even in case of cirrhosis, HCC risk is low in Wilson disease. Our data do not support regular HCC surveillance in Wilson disease. Copyright © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.",Cirrhosis;Hepatocellular carcinoma;Wilson disease;adult;alpha fetoprotein blood level;article;cancer diagnosis;cancer incidence;cancer mortality;cancer risk;cancer staging;cohort analysis;disease severity;female;follow up;human;liver cell carcinoma/co [Complication];liver cell carcinoma/di [Diagnosis];liver cirrhosis;liver transplantation;long term care;major clinical study;male;meta analysis (topic);middle aged;priority journal;retrospective study;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alpha fetoprotein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"van Meer, S.;de Man, R. A.;van den Berg, A. P.;Houwen, R. H. J.;Linn, F. H. H.;van Oijen, M. G. H.;Siersema, P. D.;van Erpecum, K. J.",2015,01 Mar,http://dx.doi.org/10.1111/jgh.12716,0,0,
1317,Effects of tetrathiomolybdate and penicillamine on brain hydroxyl radical and free copper levels: A microdialysis study in vivo,"Wilson disease is an inherited disorder of excessive copper accumulation. The commonly used drug d-penicillamine (PA) or trientine both cause a high incidence (10-50%) of neurological worsening, which rarely occurs with tetrathiomolybdate (TM) treatment. To investigate the mechanisms of neurologic deterioration after the initiation of chelation therapy, brain hydroxyl radical and free copper were assessed in vivo in this study. On days 3, 7, 14, and 21 after PA or TM administration, striatal hydroxyl radical levels of both TX mice and controls were assessed by terephthalic acid (TA) combined with microdialysis and high-performance liquid chromatography (HPLC). Within the same microdialysis samples, free copper was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that both hydroxyl radical and free copper markedly increased in the striatum of TX mice during PA administration but were not elevated when administering TM. These results suggested that the further increased free copper in the brain and oxidative stress caused by some chelators might contribute to the neurological deterioration. Copyright © 2015 Elsevier Inc. All rights reserved.",Free copper;Hydroxyl radical d-penicillamine;In vivo;Tetrathiomolybdate;Wilson disease;animal experiment;article;brain;chelation therapy;controlled study;corpus striatum;dialysate;high performance liquid chromatography;in vivo study;mass spectrometry;microdialysis;mouse;nonhuman;oxidative stress;priority journal;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];hydroxyl radical/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/to [Drug Toxicity],"Zhang, J. W.;Liu, J. X.;Hou, H. M.;Chen, D. B.;Feng, L.;Wu, C.;Wei, L. T.;Li, X. H.",2015,27 Feb,http://dx.doi.org/10.1016/j.bbrc.2015.01.071,0,0,
1318,Wilson's disease caused by alternative splicing and Alu exonization due to a homozygous 3039-bp deletion spanning from intron 1 to exon 2 of the ATP7B gene,"We describe a case of Wilson's disease (WD) diagnosed at 5. years after routine biochemical test showed increased aminotransferases. Mutation analysis of the ATP7B gene revealed a 3039-bp deletion in the homozygous state spanning from the terminal part of intron 1 to nt position 368 of exon 2. This deletion results in the activation of 3 cryptic splice sites: an AG acceptor splice site in nt positions 578-579 producing a different breakpoint and removing the first 577 nts of exon 2, an acceptor and a donor splice site in nt positions 20363-4 and 20456-7, respectively, in intron 1, resulting in the activation of a 94-bp cryptic Alu exon being incorporated into the mature transcript. The resulting alternative transcript contains a TAG stop codon in the first amino acid position of the cryptic exon, likely producing a truncated, non-functional protein. This study shows that intron exonization can also occur in humans through naturally occurring gross deletions. The results suggest that the combination of DNA and RNA analyses can be used for molecular characterization of gross ATP7B deletions, thus improving genetic counseling and diagnosis of WD. Moreover these studies help to better establish new molecular mechanisms producing Wilson's disease. Copyright © 2015 Elsevier B.V..",Alternative splicing;atp7b;Deletion;Diagnosis;Exonization;Wilson's disease;alanine aminotransferase blood level;alternative RNA splicing;Alu sequence;amino acid sequence;article;aspartate aminotransferase blood level;biochemical analysis;case report;copper metabolism;disease control;DNA determination;excretion;exon;female;gamma glutamyl transferase blood level;gene activation;gene deletion;gene mutation;genetic analysis;genetic counseling;genetic screening;hepatomegaly;homozygosity;hospital admission;human;intron;molecular genetics;priority journal;RNA analysis;stop codon;urinary excretion;Wilson disease/et [Etiology];zinc urine level;alanine aminotransferase/ec [Endogenous Compound];amino acid/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];non functional protein/ec [Endogenous Compound];penicillamine;protein/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc,"Mameli, E.;Lepori, M. B.;Chiappe, F.;Ranucci, G.;Di Dato, F.;Iorio, R.;Loudianos, G.",2015,15 Sep,http://dx.doi.org/10.1016/j.gene.2015.05.067,0,0,
1319,Costly choices for treating Wilson's disease,,aminotransferase blood level;article;ceruloplasmin blood level;chelation therapy;copper blood level;drug cost;drug industry;drug marketing;food and drug administration;human;maintenance therapy;patient compliance;priority journal;treatment failure;Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Schilsky, M. L.;Roberts, E. A.;Hahn, S.;Askari, F.",2015,01 Apr,http://dx.doi.org/10.1002/hep.27663,0,0,
1320,Secondary kinesigenic paroxysmal dyskinesias: Report of two unusual cases responsive to carbamazepine,"Paroxysmal dyskinesias represent an unusual group of movement disorders featuring intermittent involuntary paroxysmal movements including dystonia, chorea, athetosis, ballismus, or a combination of these. Secondary paroxysmal dyskinesias are rare. We report on two patients: a male with Wilson's disease who presented paroxysmal kinesigenic dyskinesias in the titration period with d-penicillamine, and a female who initially developed paroxysmal kinesigenic dyskinesias and turned out to have a subacute sclerosing panencephalitis. Carbamazepine had a remarkable beneficial effect on paroxysmal symptoms in both of them but it does not replace the treatment of the underlying illness. Copyright © 2014 Elsevier GmbH.",Carbamazepine;Paroxysmal dyskinesias;Secondary paroxysmal dyskinesias;Subacute sclerosing panencephalitis;Wilson disease;adolescent;adult;anarthria;article;asthenia;Babinski reflex;bone marrow aplasia/di [Diagnosis];bradykinesia;case report;cervical dystonia;clonus;constipation;drug dose reduction;drug withdrawal;dysarthria;dystonia;female;fever;gait disorder;hepatitis A;human;limb tremor;male;medical history;muscle rigidity;newborn jaundice;nuclear magnetic resonance imaging;Ommaya reservoir;oromandibular dystonia;paroxysmal kinesigenic dyskinesia/dt [Drug Therapy];priority journal;rash;subacute sclerosing panencephalitis/di [Diagnosis];subacute sclerosing panencephalitis/dt [Drug Therapy];urine retention;virus pneumonia;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alpha2b interferon/dt [Drug Therapy];alpha2b interferon/iv [Intravenous Drug Administration];carbamazepine/dt [Drug Therapy];etiracetam/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Raina, G. B.;Folgar, S. S.;Plumet Garrido, J.;Calvo, D. S.;Araoz Olivos, N.;Morera, N.;Moreno, M.;Uribe Roca, M. C.;Micheli, F.",2015,01 Mar,http://dx.doi.org/10.1016/j.baga.2014.12.001,0,0,
1321,Wilson's disease in association with anetoderma,"Background: Wilson's disease is an autosomal recessive disorder of copper homeostasis with predominantly hepatic and neuropsychiatric involvement. Anetoderma is a rare benign condition with focal damage of dermal elastic tissue. Previous reports described this skin disorder in association with prolonged d-Penicillamine therapy. Case presentation: A 26-year-old male was referred for evaluation of asymptomatic elevation of aminotransferase levels. Investigations showed negative markers for chronic viral and autoimmune hepatitis, low ceruloplasmin level, and increased copper urinary excretion. Liver biopsy revealed chronic hepatitis with moderate activity and severe bridging fibrosis. Mutation analysis found a compound heterozygote genotype and supported a diagnosis of Wilson's disease. At the time of the primary physical exam, skin lesions were also observed, consisting of numerous white to pale papules less than 7-8 mm in diameter with central protrusion located at the upper part of the body. Primary anetoderma was established based on presentation and skin biopsy findings. Therapy with d-Penicillamine at a daily dose of 1500 mg was started, and, during 12-month follow-up, aminotransferase decreased to normal and skin lesions remained unchanged. Conclusion: In our opinion the case is a first reported association between Wilson's disease and primary anetoderma. The possible mechanism behind this relationship is discussed. Copyright © 2015, Springer Japan.",Anetoderma;Copper;Hepatolenticular degeneration;Penicillamine;adult;alcohol consumption;anetoderma/di [Diagnosis];anetoderma/et [Etiology];anetoderma/si [Side Effect];article;atomic absorption spectrometry;case report;chronic hepatitis;disease association;disease severity;heterozygote;human;human tissue;liver biopsy;liver histology;male;mutational analysis;pathogenesis;priority journal;skin biopsy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Ivanova, I. I.;Kotzev, I. A.;Atanassova, M. V.;Gancheva, D. T.;Pavlov, S. I.;Krasnaliev, I. J.;Konstantinova, D. H.",2015,,http://dx.doi.org/10.1007/s12328-015-0550-6,0,0,105
1322,Magnetic resonance imaging improvement in a patient with Wilson's disease following treatment with trientine hydrochloride and zinc acetate. [Japanese],"A 37-year-old male patient presented with psychiatric symptoms, dysarthria, limb dystonia, increased tendon reflexes, and a Kayser-Fleischer ring in his late teens. Laboratory examinations showed decreased concentrations of serum copper and ceruloplasmin, and increased urinary copper levels. Magnetic resonance imaging (MRI) showed high-signal-intensity lesions in the bilateral putamen, globus pallidus, thalamus, and brainstem on T<inf>2</inf>-weighted images (T<inf>2</inf>WI). Based on the MRI results and laboratory data, we diagnosed this patient with Wilson's disease (WD). He was treated with trientine hydrochloride and zinc acetate. Four months after the initiation of treatment, the patient'symptoms began to improve. On a follow-up MRI that was obtained 6 years after treatment, the high-signal-intensity lesions on the T<inf>2</inf>WI had disappeared completely. However, the low-signal-intensity lesions in the basal ganglia had spread to the caudate nuclei. Here, we discuss the characteristics of the MRI changes in WD following treatment. The Pathological basis for the low-signal-intensity lesions on T<inf>2</inf>WI in WD remains unclear. Our results suggest that this lesion may reflect the accumulation of materials other than copper.",Magnetic resonance imaging;Trientine hydrochloride;Wilson's disease;Zinc acetate;adult;article;basal ganglion;brain stem;case report;caudate nucleus;copper blood level;dysarthria;dystonia;follow up;globus pallidus;histopathology;human;human tissue;laboratory test;male;mental disease;nuclear magnetic resonance imaging;putamen;symptom;tendon reflex;thalamus;treatment outcome;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Kim, Y.;Koide, R.;Kawata, A.",2015,01 May,,0,0,
1323,Wilson disease and other neurodegenerations with metal accumulations,,Chelating therapy;Manganism;nbia;Neurodegeneration with brain iron accumulation;Primary familial brain calcification;Wilson disease;acute hepatitis;acute liver failure;article;brain calcification;brain depth stimulation;cataract;ceruloplasmin blood level;chelation therapy;chronic hepatitis;computer assisted tomography;copper blood level;copper metabolism;differential diagnosis;disease association;dystonia;genetic screening;human;hypertransaminasemia;incidence;liver biopsy;liver cirrhosis;mitochondrial membrane;neurodegeneration with brain iron accumulation/di [Diagnosis];neurodegeneration with brain iron accumulation/ep [Epidemiology];neurodegeneration with brain iron accumulation/et [Etiology];neuroimaging;nonhuman;nuclear magnetic resonance imaging;onset age;ophthalmology;pathophysiology;practice guideline;prevalence;prognosis;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];calcium;ceruloplasmin;copper;fatty acid;iron;manganese;penicillamine;phospholipase;trientine;zinc,"Dusek, P.;Litwin, T.;Czlonkowska, A.",2015,,http://dx.doi.org/10.1016/j.ncl.2014.09.006,0,0,
1324,Timely diagnosis of Wilson's disease using whole exome sequencing,,ATP7B gene;Exome sequencing;Neurogenetics;Next-generation-sequencing;Wilson's disease;adult;case report;clinical feature;cognition;copper blood level;disease severity;dysarthria;exome;eye movement;female;gait;gene sequence;heterozygosity;homozygosity;human;irritability;letter;Mini Mental State Examination;Montreal cognitive assessment;pons;priority journal;red nucleus;reflex;sequence alignment;signal transduction;stereotypy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Rodriguez-Quiroga, S. A.;Rosales, J.;Arakaki, T.;Cordoba, M.;Gonzalez-Moron, D.;Medina, N.;Garretto, N. S.;Kauffman, M. A.",2015,November,http://dx.doi.org/10.1016/j.parkreldis.2015.09.031,0,0,
1325,Increased Prevalence of Subcutaneous Lipomas in Patients with Wilson Disease,"Goals: To determine the prevalence and characteristics of lipomas in patients with Wilson disease. Background: Wilson disease is an autosomal recessive disorder resulting in copper accumulation in the liver and the central nervous tissue. Subcutaneous lipomas were often noted by the authors during clinical examinations of patients with Wilson disease. This is the first study to analyze the prevalence and progression of lipoma development in patients with Wilson disease. Study: Eighty consecutive patients attending a tertiary care center were examined for the presence of subcutaneous lipomas. Results: Subcutaneous lipomas could be detected during the examination of 21 (26%) of the 80 patients with Wilson disease. Multiple subcutaneous lipomas were present in 16 (76%) of the 21 affected patients. Lipomas were mainly found on the extremities and the trunk. Neither initial presentation nor decoppering treatment influenced the presence or course of lipomas in these patients. Conclusions: Subcutaneous lipoma formation is more common in patients with Wilson disease than in the general population. We suggest that the presence of lipomas contributes to the differential diagnosis of Wilson disease. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.",atp7b;copper;lipoma;Wilson's disease;abdomen;adult;arm;article;disease association;disease course;female;genotype;head;human;leg;lipoma/dt [Drug Therapy];major clinical study;male;prevalence;priority journal;skin tumor/dt [Drug Therapy];subcutaneous lipoma/dt [Drug Therapy];subcutaneous lipoma;tertiary care center;thorax;Wilson disease;chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Schaefer, M.;Gotthardt, D. N.;Didion, C.;Stremmel, W.;Weiss, K. H.",2015,23 Jul,http://dx.doi.org/10.1097/MCG.0000000000000248,0,0,
1326,Wing Beating Tremor and Double Panda Sign,,Giant Panda sign;Wilson's disease;Wing beating tremor;adult;article;brain region;case report;ceruloplasmin blood level;echography;follow up;gait;human;kayser fleischer ring;liver function test;male;muscle hypertonia;neurologic examination;nuclear magnetic resonance imaging;priority journal;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;copper;zinc acetate/dt [Drug Therapy],"Manoj, S.;Hari Kumar, K. V. S.",2015,March 01,http://dx.doi.org/10.1002/mdc3.12134,0,0,
1327,An obese patient with disturbed liver enzymes: Not always non-alcoholic fatty liver disease. [Dutch],"Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the western world. Even in patients with several risk factors for metabolic syndrome, one has to remain vigilant and needs to exclude other causes of liver disease, such as viral hepatitis, auto-immune liver disease and storage diseases. If the treatment of NAFLD by weight loss does not result in an improvement of the disturbed liver tests, further investigation is warranted. One of the well-known mimickers of NAFLD is Wilson's disease. This is an inherited autosomal recessive disorder characterised by copper accumulation in affected tissues, mainly in the liver and brain. Liver disease in Wilson's disease can present with a broad spectrum of abnormalities, ranging from asymptomatic disturbed liver tests to liver cirrhosis and even acute liver failure. Diagnosing Wilson's disease is extremely important as the disease is - if untreated - universally fatal. The treatment consists of chelation therapy (D-penicillamine, trientine, zinc) or a liver transplantation.",acute liver failure;article;chelation therapy;human;liver cirrhosis;liver transplantation;metabolic syndrome X;nonalcoholic fatty liver;obesity;risk factor;weight reduction;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Beyls, C.;Arts, J.;Holvoet, A.;Van Hootegem, Ph;Dalle, I.;Cassiman, D.;Decock, S.",2015,15 Dec,http://dx.doi.org/10.2143/TVG.71.24.2002023,0,0,
1328,Dextromethorphan/Quinidine for Neuropsychiatric manifestations of Wilson's Disease,,adult;case report;Clinical Global Impression scale;depression;drug substitution;drug withdrawal;dystonia;female;human;impulsiveness;letter;mental instability;parkinsonism;Wilson disease/dt [Drug Therapy];dextromethorphan plus quinidine/dt [Drug Therapy];quetiapine;zinc acetate,"Faden, J.;O'Reardon, J. P.",2015,,http://dx.doi.org/10.4088/PCC.15l01820,0,0,
1329,Wilson disease. [German],"Wilson disease is an inherited disorder of copper balance leading to hepatic damage and neurological disturbance of variable degree. The mutant gene, ATP7B, encodes a copper-transporting protein, which plays a key role in human copper metabolism. Our knowledge on Wilson disease has increased dramatically; however, understanding of genotype-phenotype correlation and multifarious effects of copper toxicity as basis for targeted and individualized therapy strategies is still insufficient. Clinical manifestations include hepatic disease ranging from mild hepatitis to acute liver failure or cirrhosis and/or neurological symptoms such as dystonia, tremor, dysarthria, and psychiatric disturbances. Mixed presentations occur frequently. Early recognition by means of clinical, biochemical or genetic examination and initiation of therapy with copper chelators or zinc salts are essential for favorable outcome. Copyright © 2015 Dustri-Verlag Dr. Karl Feistle.",atp7b;Copper;Inherited disease;Liver;Neurologic disorder;ATP7B gene;copper metabolism;dysarthria;dystonia;gene;genotype phenotype correlation;human;liver cirrhosis;liver injury;neurologic disease;review;tremor;Wilson disease/dt [Drug Therapy];copper/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy],"Huster, D.",2015,November,http://dx.doi.org/10.5414/VDX00883,0,0,
1330,A case of trientine overdose,Wilson disease is a rare genetic hepatic and neurological disorder of copper accumulation. Trientine is usually used as a second line in the management of patients with this condition. We present a case of a large overdose of Trientine (60 g) resulting in self-limiting dizziness and vomiting with no further clinical sequelae or significant biochemical abnormalities. This case shows that Trientine has a good safety profile and hence could be used as a first line treatment in patients with Wilson's disease who suffer from psychiatric complications and who might be at risk of self-harm. Copyright © 2015 Toxicology International.,Overdose;trientine;Wilson's disease;acute kidney failure;article;case report;copper blood level;dizziness;drug overdose;drug safety;human;hypophosphatemia;liver cirrhosis;portal hypertension;suicide attempt;thrombocytopenia/co [Complication];tremor;unspecified side effect/si [Side Effect];vomiting;Wilson disease/dt [Drug Therapy];zinc blood level;copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];phosphate/ec [Endogenous Compound];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];zinc/ec [Endogenous Compound],"Hashim, A.;Parnell, N.",2015,January-April,http://dx.doi.org/10.4103/0971-6580.172262,0,0,
1331,Drug-induced elastosis perforans serpiginosa,,adult;case report;disease association;disease duration;drug induced disease/si [Side Effect];drug induced elastosis perforans serpiginosa/si [Side Effect];drug induced elastosis perforans serpiginosa;drug substitution;drug withdrawal;erythaematous keratotic papule;female;hair follicle;human;human tissue;medical history;note;papule;physical disease by anatomical structure;priority journal;skin biopsy;skin disease/si [Side Effect];skin laxity;treatment duration;Wilson disease/dt [Drug Therapy];collagen/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Menzies, S.;Kirby, B.",2015,07 Dec,http://dx.doi.org/10.1136/bcr-2015-212482,0,0,
1332,"A case of Wilson's disease with psoriasis vulgaris, complicated with hepatocellular carcinoma and successfully treated with sorafenib. [Japanese]","A 55-year-old man had been diagnosed with Wilson's disease and was treated with D-penicillamine 36 years earlier. He also had a 20-year history of psoriasis vulgaris and cyclosporine treatment. In 2012, a he presented with a hepatocellular carcinoma (HCC) that was removed via partial hepatic resection. In 2014, multiple HCC and a portal vein tumor thrombus were found in his posterior lobe. Sorafenib treatment was initiated. Cyclosporine treatment was continued. Three months later, abdominal enhanced CT revealed marked tumor reduction and shrinkage of the portal vein tumor thrombus. The therapeutic effect of sorafenib continued for 6 months. We did not observe deterioration in his psoriasis vulgaris and Wilson's disease for 9 months after sorafenib initiation.",Hepatocellular carcinoma;Sorafenib;Wilson's disease;adult;article;cancer surgery;case report;computer assisted tomography;human;liver cell carcinoma/co [Complication];liver cell carcinoma/dt [Drug Therapy];liver cell carcinoma/su [Surgery];liver resection;male;middle aged;portal vein tumor thrombus;psoriasis vulgaris/dt [Drug Therapy];therapy effect;treatment outcome;treatment response;tumor thrombus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];sorafenib/dt [Drug Therapy];sorafenib/pd [Pharmacology],"Nakagawa, T.;Chubachi, S.",2015,September,,0,0,
1333,Elevated serum brain natriuretic peptide and matrix metalloproteinases 2 and 9 in Wilson's disease,"Wilson's disease (WD) is a disease of copper metabolism characterized by excessive copper deposition in the body. It is reported abnormal copper metabolism has been associated with cardiovascular disease. BNP and MMP2/9 were biomarkers of congestive heart failure (CHF). There is rare study to explore whether serum concentrations of BNP, MMP2, and or MMP9 are altered in patients with WD. In this study we determine whether serum concentrations of brain natriuretic peptide (BNP) and matrix metalloproteinases (MMP) 2 and 9 are increased in patients with WD. Serum BNP, MMP2 and MMP9 were measured by an ELISA in 34 patients with hepatic WD, in 68 patients with neurological WD, and in 33 healthy controls. We found serum BNP levels were higher in patients with neurological WD than in healthy controls (p = 0.033). Serum MMP2 levels were higher in patients with hepatic (p = 0.009) and neurologic (p = 0.0004) WD than in controls. Serum MMP9 levels were higher in patients with neurologic WD than in patients with hepatic WD (p = 0.002) and controls (p = 0.00005), and were higher in patients with hepatic WD than in controls (p = 0.03). Serum BNP levels were negatively correlated with ceruloplasmin (p = 0.017, r = -0.215), while serum (p = 0.019, r = -0.221) and MMP9 (p = 0.011, r = -0.231) in patients with WD were negatively correlated with ceruloplasmin. BNP, MMP2, and MMP9 may reflect the deposition of copper in the heart. Copyright © 2015, Springer Science+Business Media New York.","bnp, mmp2;Cardiovascular dysfunction;mmp9;Wilson's disease;adult;article;clinical assessment;clinical evaluation;concentration process;controlled study;copper metabolism;enzyme linked immunosorbent assay;female;human;liver disease;major clinical study;male;neurologic disease;outcome assessment;protein analysis;protein blood level;Wilson disease/di [Diagnosis];brain natriuretic peptide/ec [Endogenous Compound];ceruloplasmin;copper;gelatinase A/ec [Endogenous Compound];gelatinase B/ec [Endogenous Compound];gluconate zinc;penicillamine","Cheng, N.;Wang, H.;Dong, J.;Pan, S.;Wang, X.;Han, Y.;Yang, R.",2015,01 Aug,http://dx.doi.org/10.1007/s11011-015-9685-x,0,0,
1334,Cholestatic liver disease masquerading as Wilson disease,"Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 mug/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement. Copyright © 2015, Indian Society of Gastroenterology.",Ceruloplasmin;Cholestatic liver disease;Sclerosing cholangitis;adolescent;article;case report;chelation therapy;child;female;human;human tissue;liver biopsy;liver disease;male;nutritional support;receiver operating characteristic;school child;sensitivity and specificity;Wilson disease;bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine;ursodeoxycholic acid;zinc,"Sood, V.;Rawat, D.;Khanna, R.;Alam, S.",2015,05 May,http://dx.doi.org/10.1007/s12664-015-0552-9,0,0,
1335,Therapeutic efficacy of D-penicillamine nanoparticles in rat model of non-wilsonian brain copper toxicosis,"Animal models of Wilson's disease (WD) viz. Long evans cinnamon rats, rarely exhibit neurological symptoms impeding the development of novel therapeutic approaches to treat neurological manifestationsin WD patients. The aim of this study was to examine the effect of intraperitoneally injected copper lactate for 90 days especially on copper and zinc levels in liver, kidney & brain tissues; expression of hepatic metallothionein-I (MT-I) and Atp7b gene; and MT-III and acetylcholine esterase (AChE) gene in brain, biochemical parameters, and neurobehavioral functions of male Wistar rats, and therapeutic evaluation of orally administered D-penicillamine encapsulated alginate/chitosan nanoparticles for 90 days on Cu intoxicated Wistar rats. Reverse transcription-PCR and Morris water maze test were used for expression and neurobehavioral studies. Copper intoxicated animals showed significantly increased ceruloplasmin, serum & urine copper levels and decreased serum acetyl choline esterase (AChE) activity, increased expression of hepatic MTI gene with impaired neuromuscular coordination and spatial memory. However, no changes were observed on the expression levels of hepatic Atp7b gene; and MT-III and AChE gene in brain. Cu intoxicated rats revealed a significant increase in the liver, brain and kidney tissues copper content (99.1, 73 and 74.9 % increase respectively), decreased liver zinc (40% decrease) & interestingly, increased brain zinc content (77.1% increase) compared to controls rats. Histopathological studies demonstrated grade 4 copper depositions in the liver and grade 1 copper associated protein in liver tissues of test rats by rhodanine and orcein stains respectively. Astrocytes swelling were observed in cerebral cortex sections of brain tissues of Cu intoxicated rats. D-penicillamine encapsulated alginate/chitosan nanoparticles therapy resulted in significant reduction of liver and brain Cu content, serum ceruloplasmin level & increase in serum AChE activity with improvement in neurological functions. In conclusion, chronic copper toxicity may lead to increased copper content in liver & brain, increased hepatic MT-I gene expression, ceruloplasmin levels and, neurobehavioral impairments may be by interfering in acetylcholine modulated neurotransmission; however, D-penicillamine encapsulatednanoparticles may reverseimpairments caused by chronic Cu intoxication to a significant extentin Wistar rats.",rat;rat model;brain;intoxication;India;therapy;liver;gene;serum;Wistar rat;brain tissue;swelling;astrocyte;kidney;histopathology;kidney parenchyma;spatial memory;human;urine;patient;Morris water maze test;male;neurologic disease;reverse transcription polymerase chain reaction;Long Evans cinnamon rat;parameters;stain;animal model;neurotransmission;brain cortex;gene expression;toxicity;ceruloplasmin blood level;Wilson disease;penicillamine;nanoparticle;copper;zinc;acetylcholine;ceruloplasmin;metallothionein I;rhodanine;cholinesterase;protein;acetylcholinesterase,"Pal, A.;Badyal, R.;Vasishta, R. K.;Attri, S. V.;Thapa, B. R.;Prasad, R.",2015,December,http://dx.doi.org/10.1007/s12291-015-0537-6,0,0,
1336,Surviving a Wilsonian crisis without liver transplantation,"Introduction: Wilson's Disease (WD), a disorder of copper excretion, is a rare but important indication for urgent liver transplantation. Chelation therapy is ineffective in acute Wilsonian crisis, necessitating liver transplantation as the treatment of choice. Case Report: A 19 year old female presented to the ED after feeling weak, fatigued, complaining of RUQ abdominal pain and hematuria for 5 days. She experienced increasing weakness over the last 4 months, loss of singing voice, and had symptoms of biliary colic with fatty foods. She recently started on birth control, but had no other past medical history. On admission she was jaundiced with total bilirubin 10.8, direct bilirubin 3.1, AST 177, ALT 11, Alkaline Phosphatase 8, Albumin 3.4, INR 1.6, hemoglobin 6.6, MCV 112, white blood cell 18.0, platelets 195, Creatinine 1.47, bilirubinuria, and bilateral pleural effusions. Abdominal ultrasound revealed ascites, dilated common bile duct, and biliary sludge. She was admitted to the PICU. She had a coombs-negative hemolytic anemia, requiring seven units of blood in seven days. She had a paracentesis on day two with a SAAG consistent with portal hypertension. The patient underwent an extensive workup while hospitalized with no answers and on day three she was empirically started on steroids. Her ceruloplasmin was 21, which is low normal. She underwent a liver biopsy during cholecystectomy for persistent RUQ pain, showing cirrhosis and swollen glycogen rich hepatocytes, suggestive of glycogen storage disease; this returned after her discharge. She recovered from the hemolytic anemia and was sent home on day fourteen with steroids. She followed up with GI and 24 hour urine copper was ordered finding 144mug of copper. Prompt ophthalmology referral revealed Kayser-Fleisher rings. She was diagnosed with WD and started on Trientine. Follow up labs revealed decreasing urinary copper, gene mutation of ATP7B, and improvement of her singing voice and fatigue. This case represents an often fatal presentation of WD without transplant. This patient survived without transplantation and I question if steroids played a role in her improvement without transplant. It also serves as a reminder of the complexity of recognizing WD in the acute setting.",liver transplantation;American;college;gastroenterology;human;transplantation;singing;hemolytic anemia;voice;patient;hematuria;abdominal pain;chelation therapy;sludge;medical history;food;biliary colic;ultrasound;thrombocyte;liver cell;liver cirrhosis;glycogen storage disease;pleura effusion;gene mutation;ascites;common bile duct;birth control;female;diseases;cholecystectomy;leukocyte;blood;paracentesis;portal hypertension;weakness;liver biopsy;pain;urine;ophthalmology;follow up;case report;fatigue;excretion;mean corpuscular volume;international normalized ratio;Wilson disease;copper;steroid;alkaline phosphatase;bilirubin;n [bis(1 aziridinyl)phosphinyl] 4 iodobenzamide;bilirubin glucuronide;albumin;creatinine;ceruloplasmin;hemoglobin;glycogen;trientine,"Mohrhardt, L. S.;Wisser, K.",2015,October,http://dx.doi.org/10.1038/ajg.2015.270,0,0,
1337,"A Nationwide, population-based epidemiology and disease burden of wilson 's disease in South Korea in 2009-2013","Background/Aims: Wilson's disease (WD) is an inherited autosomal recessive disorder of copper metabolism in which copper accumulates in the organ, particularly in the liver and the central nervous system. As a rare disease, population-based epidemiology of WD is largely unknown. This study aimed to investigate the nationwide, population-based prevalence, comorbidity, treatment regimen, and direct medical cost of WD in South Korea from 2009 to 2013. Methods: Using 2 big data source from Health Insurance Review and Assessment Service (HIRA) claims database and Rare Intractable Diseases registration program database from 2009 to 2013 in Korea, we identified all patients with WD registered by physician as the International Classification of Diseases (ICD-10) code for WD (E83.0), and with the registration record (V174) for the rare disease in Korea. The five-year data included 1,509 patients linked with information including age, gender, comorbidity ICD-10 codes, prescribed medications, and direct medical costs. Results: The overall crude prevalence of WD was 2.38/100,000 people and it showed increasing tendency during the 5 years (2.27, 2.28, 2.35, 2.45, and 2.53/100,000 at 2009-2013, respectively). Most (72%) patients were diagnosed before 30 years old, and 1.4% had additional disease code for neurologic/ psychologic disease. Liver cirrhosis and liver cancer were detected in 33.2% and 9.9%, respectively. Liver transplantation was performed in 4.6% of patients. D-penicillamine, trientine, and zinc were prescribed for 58.3%, 29.7%, and 13.9% of patients, respectively. Mean annual total medical cost per person for WD was 1,643.15 USD. Conclusion: The prevalence of WD was slightly lower in Korean than other countries, showing an increase from 2009. Since about one third of WD patients had advanced liver disease such as cirrhosis and cancer, more efforts for early diagnosis and treatment for WD are warranted, especially during pediatric age.",epidemiology;American;population;liver;liver disease;South Korea;Wilson disease;human;patient;prevalence;comorbidity;liver cirrhosis;data base;icd-10;rare disease;Korean (people);Korea;registration;physician;liver transplantation;liver cancer;diseases;copper metabolism;health insurance;drug therapy;gender;neoplasm;early diagnosis;International Classification of Diseases;central nervous system;autosomal recessive disorder;zinc;trientine;penicillamine;copper,"Baeg, J. Y.;Jang, E. S.;Ki, M. R.;Kim, B. H.;Kim, K. A.;Choi, H. Y.;Jeong, S. H.",2015,October,http://dx.doi.org/10.1002/hep.28239,0,1,
1338,Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines,"Objective: To assess in vitro functional analysis and drug response to zinc (Zn) and D-penicillamine (DPA) treatment of most common disease-causing ATP7B mutations observed in Wilson disease (WD) patients. Background: WD is a rare autosomal recessive disorder caused due to mutations in the copper transporter ATP7B. More than 600 disease-causing mutations are described. If not treated, WD is fatal. Commonly used drugs to reverse Cu toxicity in WD include direct chelation by DPA or metallothionein induction using Zn salts. The impact of these drugs in rescuing hepatocytes carrying individual mutations is unknown. Methods: Frequent homozygous mutations in Europe/US, Asia, and India were selected for functional analysis. An ATP7B knockout hepatic cell line previously established by our group (PLoS ONE, 9: e98809, 2014) was used to generate stable mutant cell lines. ATP7B gene and protein expression were determined for all mutant cell lines. Cu induced cell survival, apoptosis, and intracellular trafficking were studied. Cell viability against Cu toxicity was determined on treatment with Zn, DPA, or both. Results: ATP7B mRNA was similar whereas protein expression varied among the different mutant cell lines. Co-localization studies with late endosome lysosome marker lamp2 suggested impaired trafficking in presence or absence of Cu. All mutant cell lines showed different grades of ATP7B activity against Cu induced toxicity and apoptosis with p.H1069Q displaying moderate ATP7B activity. On treatment with Zn, DPA, or both most cell lines showed a characteristic response to treatment. DPA was more effective than Zn in rescuing cells against Cu toxicity. Only combination with Zn and DPA treatment was able to rescue the mutant cells similar to wild-type. Conclusions: The study provided insights into genotype- phenotype correlation in WD. Different ATP7B mutations showed varying sensitivity to Cu with high/moderate and low ATP7B activity. Individual ATP7B mutations showed a genotype- specific response to treatment. Combination treatment with Zn and DPA showed maximal survival of hepatic cells. Our data suggest that prognosis of WD patients may benefit from knowledge of mutation-specific in vitro functional analysis and use of Zn/DPA combination therapy.",mutant;liver cell;cell line;American;liver disease;liver;drug response;mutation;cell mutant;toxicity;protein expression;patient;apoptosis;human;in vitro study;therapy;Asia;prognosis;chelation;survival;genotype;wild type;lysosome;autosomal recessive disorder;Wilson disease;cell viability;endosome;cell survival;genotype phenotype correlation;gene;India;zinc;penicillamine;metallothionein;marker;copper;messenger RNA,"Chandhok, G.;Sauer, V.;Niemietz, C.;Zibert, A.;Schmidt, H. H.",2015,October,http://dx.doi.org/10.1002/hep.28239,0,0,
1339,Hepatocellular carcinoma in patients with wilson's disease: Results of a single centre registry of 262 patients,"Introduction: Although hepatocellular carcinoma (HCC) is a well recognized complication of cirrhosis of various etiologies, HCC is believed to be extremely rare in Wilson disease. Around 30 cases have been reported worldwide illustrating the rarity of this complication. We undertook this study to determine the frequency and characteristics of HCC in a cohort of 262 patients over 19 years Patients and methods: We reviewed the case records of patients with Wilson disease from the Wilson disease registry maintained from 1996 to 2014. Diagnosis of Wilson disease was based on a score > 4 developed by the International group at Leipzig (J Hepatol 2012;56:671-85). Patients were treated with D-penicillamine with or without Zinc Sulfate. Patients were regularly followed up at 3-6 monthly intervals. Patients with HCC were initially assessed by ultrasonography of abdomen followed by a contrast enhance CT scan. Results: We identified 3 cases of HCC among 262 patients with Wilson disease. All 3 had cirrhosis with portal hypertension at the time of diagnosis as evidenced by esophageal varices and ascites. The characteristics of these patients are depicted in Table. All three had multicentric HCC and presented with resistant complications of portal hypertension such as variceal bleeding, resistant ascites and one with hemoperitoneum. Given the advanced nature of HCC at presentation only supportive treatment could be given. Conclusions: The incidence of HCC in a large cohort of 262 patients is 1.1%. Although low, patients with WD are also at risk for HCC. HCC appears to be aggressive in our cohort of Wilson disease. Patients with Wilson disease need to undergo regular screening for early detection of HCC similar to other etiologies. Those who are insufficiently chelated appear to be more at risk for HCC. (Table Presented).",human;patient;liver cell carcinoma;register;American;liver disease;liver;Wilson disease;liver cirrhosis;ascites;portal hypertension;risk;diagnosis;etiology;screening;disease registry;hemoperitoneum;bleeding;esophagus varices;computer assisted tomography;abdomen;echography;penicillamine;zinc sulfate,"Devarbhavi, H.;Patil, M.",2015,October,http://dx.doi.org/10.1002/hep.28239,0,0,
1340,Zinc monotherapy for young pediatric patients with presymptomatic wilson disease: A two-center experience in Japan,"Purpose: We previously reported that a reasonable goal in treating young pediatric patients with Wilson disease (WD) using zinc to be maintaining 24-hour urinary copper excretion between 1 and 3 mug/kg/day for the first 1-2 years (Mizuochi, et al. JPGN 2011;53:365). Here, we aimed at evaluating long-term efficacy and safety of zinc monotherapy for young pediatric patients with WD and establishing appropriate benchmarks of maintenance therapy. Methods: We performed a retro- and prospective study to examine 7 girls (median age 5 years, range 4-8) who satisfied diagnostic criteria for WD and were treated solely with zinc acetate prior to symptom onset at Kurume University Hospital and Okinawa Chubu Hospital in Japan. No additional WD sequelas, such as jaundice, hepatomegaly, or neurologic abnormalities were noted. We monitored serum AST and ALT, nonceruloplasmin serum copper, and 24-hour urinary copper for 2-7 years after initiation of zinc monotherapy. Additional monitorings included white blood cell count, hemoglobin, platelet count, serum total bilirubin, albumin, iron, amylase, lipase, and prothrombin time, as well as 24-hour urinary zinc excretion. We performed abdominal ultrasonograpy and evaluated clinical WD manifestations, drug compliance, and adverse effects of zinc. The prescribed dosage of zinc acetate for patients <= 5 years 25 mg twice daily; for those children 6 years or older, the dose was 25 mg 3 times daily. We increased the dosage of zinc if the patients had AST/ALT > 50 U/L, and decreased it if they had adverse effects of zinc such as iron-deficiency anemia or pancytopenia. Results: At the time of diagnosis, AST/ALT and 24-hour urinary copper were 207+/-182/292+/-211 U/L and 143+/-68 mug/day (7.2+/-3.5 mug/kg/day), respectively. All patients continued to take zinc without any evidence of zinc toxicity. None of our 7 patients became clinically symptomatic. AST/ALT sharply decreased to 35+/-7/37+/-16 U/L at 1 year after treatment and was mostly maintained less than 50U/L for the remainder of the study (AST/ALT: 35+/-9/42+/-29 and 33+/-9/41+/-17 U/L at 2 and 6 years after treatment, respectively). Twenty four-hour urinary copper decreased to 54+/-18 mug/day (2.3+/-0.6 mug/ kg/day) at 1 year after treatment and was mostly maintained between 1 and 3 mug/kg/day for the remainder of the study (1.7+/-0.7 and 1.9+/-0.9 mug/kg/day at 2 and 6 years after treatment, respectively). Conclusions: Long-term zinc monotherapy for young pediatric patients with presymptomatic WD proved highly effective and safe. A reasonable goal in treating young children with WD using zinc appears to be maintaining both AST/ALT under 50 U/L and 24-hour urinary copper excretion between 1 and 3 mug/kg/day.",monotherapy;patient;human;Wilson disease;Japan;American;liver disease;liver;child;serum;excretion;adverse drug reaction;zinc urine level;diagnosis;copper blood level;pancytopenia;hepatomegaly;jaundice;toxicity;iron deficiency anemia;medication compliance;hospital;university hospital;prothrombin time;girl;thrombocyte count;prospective study;leukocyte count;maintenance therapy;safety;female;zinc;copper;zinc acetate;triacylglycerol lipase;amylase;iron;albumin;bilirubin;hemoglobin,"Eda, K.;Iwama, I.;Takeuchi, T.;Takaki, Y.;Mizuochi, T.",2015,October,http://dx.doi.org/10.1002/hep.28235,0,0,
1341,The effect of treatment with chemical chaperones and zinc acetate on hepatocytes treated with excess copper,"[Purpose] Copper is an essential trace element in human activity. But excess copper gives harm to human activity. Wilson disease is a genetic disorder characterized by excess copper deposition in various organs. Excess copper-derived oxidants contribute to progression of liver disease in Wilson disease. Oxidative stress induces accumulation of abnormal proteins. The endoplasmic reticulum (ER) is subcellular organelle which plays the role of proper protein folding. Accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. Zinc acetate has been commonly used to treat Wilson disease, because it increases metallothionein production and inhibits absorption of copper in the intestinal epithelia. The effects of chemical chaperones and zinc acetate on copper-induced hepatotoxicity have not been examined. In this study, we evaluated the effects of chemical chaperone and zinc acetate on copper- induced disruption of cell homeostasis. [Methods] We used human hepatoma cell line (Huh7) and immortalized human hepatocyte cell line (OUMS29). The following materials were used: copper sulfate; acetyl-leucyl-leucyl-norleucinal and epoxomicin as proteasome inhibitors (PIs); bathocuproine disulfonate as copper chelator; n-acetyl-l-cysteine; zinc acetate; 4-phenylbutyrate (PBA) and ursodeoxycholic acid (UDCA) as chemical chaperones. We detected the reactive oxygen species using 2',7'-dichlorodihydrofluorescein. We analyzed copper-induced ER stress by immunoblotting for ER stress markers, including phospho alpha-subunit of eukaryotic initiation factor 2 and X-box binding protein 1. Hepatocyte apoptosis treated with copper with or without PI was determined by detection of cleaved poly ADP-ribose polymerase and cleaved caspase 3 by immunoblotting analysis and immunofluorescence staining, respectively. Furthermore, we examined cell proliferation on excess copper by immunofluorescence staining using Ki67. [Results] Excess copper induced oxidative stress and ER stress. Chemical chaperones and zinc acetate reduced copper-induced oxidative stress and ER stress. Co-treatment of copper and PI exacerbated copper-induced apoptosis. Although excess copper leaded to reduction in cell proliferation, chemical chaperones rescued the proliferation block in cells treated with copper. However zinc acetate did not exert this effect. [Conclusions] Excess copper induced hepatotoxicity. Chemical chaperones, PBA and UDCA, and zinc acetate reduced hepatotoxicity. These results suggest that chemical chaperones may have beneficial effects for the treatment of Wilson disease. On the other hand, zinc acetate used as the treatment of Wilson disease may inhibit liver injury directly.",liver cell;American;liver disease;liver;human;endoplasmic reticulum stress;Wilson disease;oxidative stress;liver toxicity;apoptosis;homeostasis;immunoblotting;cell proliferation;staining;immunofluorescence;human activities;protein folding;cell organelle;endoplasmic reticulum;cell line;hepatocellular carcinoma cell line;liver injury;intestine epithelium;absorption;genetic disorder;zinc acetate;copper;chaperone;protein;dichlorodihydrofluorescein;X box binding protein 1;metallothionein;initiation factor 2;marker;ursodeoxycholic acid;4 phenylbutyric acid;acetylcysteine;reactive oxygen metabolite;chelating agent;proteasome inhibitor;epoxomicin;copper sulfate;trace element;oxidizing agent;caspase 3;nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase;adenosine diphosphate,"Oe, S.;Miyagawa, K.;Honma, Y.;Harada, M.",2015,October,http://dx.doi.org/10.1002/hep.28214,0,0,
1342,Is serum copper concentration related to implantation?,"OBJECTIVE: Copper-containing contraceptive devices have been thought to cause deposition of copper ions in the endometrium resulting in implantation failure. Similarly, patients with untreated Wilson's disease usually showed subfertility and/or early pregnancy loss. Such patients treated with zinc delivered babies successfully. These observations lead a hypothesis that infertile patients with high serum copper concentrations may cause implantation failure. This study is to investigate whether serum copper concentration is related to pregnancy rate of human embryo in vivo. DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 408 patients, average age 34.2 years, who undertook freeze and thaw embryo transfer between December, 2014 and March, 2015, with the same hormone replacement cycle protocol (with Estradiol >140 pg/mL, Progesterone > 10 ng/mL at the day of transfer), with good blastocyst (3BB or more with Gardner's classification), were included in the study. Pregnancy test (serum hCG), serum copper, zinc and ceruloplasmin concentrations were measured 16 days after the first date of progesterone replacement. Hundred women with pregnant without miscarriage at 10 weeks of gestation (group P) and 176 women without pregnant (group NP) were compared. Student's t test was used for comparison between two groups. Cutoff line was determined by receiver-operator characteristic (ROC) curve, and Chi-squared test was used for 2x2 contingency table. Statistical significance was defined as P <0.05. RESULTS: Age was not different between two groups. Copper concentration of group NP (average 192.3mg/dL) was significantly higher than that of group P (average 179.7mg/dL), and zinc concentration of group NP (average 75.5mg/dL) was significantly lower than that of group P (average 90.3mg/dL). All patients showed normal ceruloplasmin level (average 39.4 mg/dL) denying Wilson's disease. According to the ROC curve of copper concentration and pregnancy outcome, the negative/positive cutoff was set at 159/160 (P=0.004 with Chi-squared test). With this cutoff, sensitivity, specificity, positive predictive value and negative predictive value were, 0.88, 0.26, 0.68, and 0.54, respectively. Copper concentration was not related to either age, estradiol, progesterone, or hCG. CONCLUSIONS: Serum high copper levels may be independent risk factor for implantation failure. A prospective study is necessary to reveal causal relationship.",implantation;American;society;reproduction;copper blood level;human;female;patient;serum;predictive value;risk factor;first trimester pregnancy;endometrium;hormone substitution;receiver operating characteristic;pregnancy outcome;prospective study;subfertility;embryo transfer;Student t test;retrospective study;spontaneous abortion;human embryo;pregnancy rate;pregnancy;pregnancy test;contingency table;statistical significance;Wilson disease;classification;blastocyst;hypothesis;baby;contraceptive device;copper;zinc;progesterone;ceruloplasmin;chorionic gonadotropin;estradiol;copper ion,"Matsubayashi, H.;Kitaya, K.;Yamaguchi, K.;Nishiyama, R.;Takaya, Y.;Ishikawa, T.",2015,September,,0,0,
1343,Fatal copper toxicity despite early aggressive interventions,"Background: Copper sulfate (CuSO4) is highly toxic at doses of 0.15-0.3 g/kg with ensuing hemolysis and multi-organ failure. There is no consensus on the optimal means for enhanced elimination in cases of severe copper (Cu) toxicity. Case presentation: A 19 year old female ingested > 10g of CuSO4 solution, obtained from her mother who was as a chemist. She had abdominal pain and blue emesis. Exam revealed hyper-salivation and tachycardia. She was intubated due to hypoxia and aspiration. Early bronchoscopy revealed tracheobronchitis and segmental bronchial blue-green staining which was irrigated for decontamination. Endoscopy revealed grade-2 esophagitis, gastritis, duodenitis, and ulcerations. Late on hospital day 1, she developed significant hemolysis, methemoglobinemia, and anuric renal failure. She was started on penicillamine 1.5 g due to a national shortage of calcium disodium edetate and dimercaprol. Trientine was unavailable. She was treated with hemodialysis (HD), exchange transfusions, methylene blue, zinc, and folate. Blood drawn in the ED, resulted on hospital day 3, revealed a serum Cu level of > 500 mug/dL. Cu was undetectable in dialysate after two courses of HD. Her renal function failed to improve and her neurological status deteriorated despite decreased serum Cu levels. After 14 days, given her unimproved clinical status, her family withdrew care. An autopsy was not performed. Discussion: Our patient manifested severe toxicity after a large ingestion of CuSO4. Bronchial irrigation provided some decontamination. HD was initiated to mitigate direct Cu- and penicillamineinduced nephrotoxicity and support renal function. There was no penicillamine-bound Cu in the dialysate. Blood product replacement and exchange transfusions may have contributed to reducing Cu burden. Serum Cu on day 8 had doubled from day 3, which may represent redistribution. Conclusions: Acute Cu toxicity is rare but carries a high mortality due to severe hemolysis and multi-organ toxicity. Penicillamine is the standard of care in cases of chronic Cu toxicity in Wilson's disease. There is no evidence as to an optimal chelator for acute toxicity but calcium disodium edetate and dimercaprol have been used successfully. In our case, despite decontamination measures, early multi-organ support, chelation, and attempts at enhanced elimination, the patient died.",Heavy metals;Copper;Chelation;toxicity;North American;toxicology;serum;human;waste management;hemolysis;blood;dialysate;patient;female;exchange blood transfusion;kidney function;hospital;bronchoscopy;aspiration;kidney failure;hypoxia;duodenitis;tachycardia;gastritis;salivation;ulcer;methemoglobinemia;esophagitis;endoscopy;vomiting;consensus;staining;tracheobronchitis;abdominal pain;hemodialysis;autopsy;mother;ingestion;nephrotoxicity;mortality;health care quality;acute toxicity;Wilson disease;heavy metal;penicillamine;dimercaprol;edetate calcium disodium;copper sulfate;n [bis(1 aziridinyl)phosphinyl] 4 iodobenzamide;methylene blue;zinc;folic acid;trientine;chelating agent,"Eisnor, D.;Anwar, M.;Morgan, B.;Pomerleau, A.",2015,,http://dx.doi.org/10.3109/15563650.2015.1071025,0,0,
1344,MEDNIK syndrome: Clinical and biochemical delineation of the response to long-term zinc therapy-A case report,"Background: MEDNIK syndrome - acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia - is caused by mutations in AP1S1 gene, encoding the sigma 1A subunit of adaptor protein complex- 1 (AP-1). AP-1 directs the intracellular trafficking of several transmembrane proteins, including the copper-transporting ATPases, ATP7A and ATP7B. We recently identified disordered copper metabolism in MEDNIK syndrome, a picture combining abnormalities of both Menkes and Wilson diseases, partially ameliorated by zinc acetate therapy. Methods: To confirm our previous observation, we performed serial clinical and biochemical evaluations in one Italian MEDNIK syndrome patient under zinc therapy. Length of treatment was 4 years. Results: Our patient presented at diagnosis with hepatopathy, hypocupremia, hypoceruloplasminemia, increased urinary copper excretion, liver copper overload, intrahepatic cholestasis. At the end of the follow-up she showed striking improvement of hepatopathy and enteropathy, with complete normalization of serum transaminases and liver copper content. However, skin abnormalities worsened during the follow-up, and she showed stagnation of cognitive development. Conclusions: The above findings pose new questions about the clinical and biochemical effects of AP-1 dysfunction and the possible therapeutic options. Chronic zinc acetate may protect affected patients from hepatic copper overload, but some copper may be required for normal brain growth and maturation.",human;therapy;case report;society;metabolism;patient;follow up;enteropathy;liver disease;liver;ichthyosis;mental deficiency;congenital skin disease;copper metabolism;Wilson disease;gene;mutation;neuropathy;excretion;keratoderma;diagnosis;intrahepatic cholestasis;treatment duration;aminotransferase blood level;hearing impairment;cognitive development;brain growth;maturation;zinc;copper;zinc acetate;copper exporting adenosine triphosphatase;membrane protein;adaptor protein,"Martinelli, D.;Dionisi-Vici, C.",2015,September,http://dx.doi.org/10.1007/s10545-015-9877-x,0,0,
1345,Wilson disease. Further evidence of phenotypic heterogeneity in two sisters,"Wilson disease (WD), is an autosomal recessive disorder caused by mutations in the ATP7B gene on 13q14.3. Defective protein leads to low ceruloplasmin blood levels and copper accumulation in liver, basal ganglia and cornea with clinical evidence of liver disease, tremors, dysarthria, dystonia and psychiatric signs. Haemolytic anemia, hypertransaminasemia, renal tubular acidosis are other common findings. We report on a series of 21 patients, aged 8 to 52 years with a long follow up under treatment with penicillamine, zinc or both. A striking phenotypic variability was observed in two sisters carrying the same genotype (c.3207C->A(p.H1069Q) / c.3904-2A->G). Although both started to present with signs at age 10 years, onset was characterized by neurological signs in the first (tremors, motor incoordination, language and cognitive impairment) whilst liver involvement is the only sign in the other. After a 20 year follow-up the former is severely affected (MRI evidence of basal ganglia copper deposits and hyperchogenic liver, piastrinopenia), while the latter still has moderate liver enlargement. This phenotypic variability could be explained by the intervention of modifier genes (CTR1, ATOX1, MURR1) regulating copper metabolism in the presence of defective ATP7B protein function. Further investigations on their role might have a profound impact also on therapy.",Wilson disease;society;metabolism;liver;follow up;tremor;basal ganglion;human;kidney tubule acidosis;hepatomegaly;hypertransaminasemia;modifier gene;copper metabolism;therapy;patient;ceruloplasmin blood level;anemia;dystonia;dysarthria;genotype;neurologic disease;language;cognitive defect;liver disease;cornea;gene;protein function;mutation;autosomal recessive disorder;copper;zinc;protein;penicillamine,"Fiumara, A.;Sapuppo, A.;Brafa Musicoro, V.;Lepori, M. B.;Loudianos, G.;Raudino, F.;Bertino, G.",2015,September,http://dx.doi.org/10.1007/s10545-015-9877-x,0,0,
1346,Hand stereotypies in Wilson's disease,"Objective: We present case study of young patient with diagnosis of Wilson's disease (WD) presenting with stereotypies in both hands. Background: Stereotypies are a phenomenological category of hyperkinetic Movement Disorders. The exact definition of stereotypy varies with different authors. It is described as coordinated, patterned, repetitive, rhythmic, purposeless but seemingly purposeful or ritualistic, movement, posture or utterance (Jankovic 1994). In an attempt to distinguish stereotypies from tics and other repeated Movement Disorders, described as ""a non-goal-directed movement pattern that is repeated continuously for a period of time in the same form and on multiple occasions, and which is typically distractible."" (Edwards et al 2013). Wilson's disease is disorder of copper metabolism with excessive accumulation of copper in basal ganglia. Hyperactive Movement Disorders seen in WD includes dystonia (frequently evident in face, jaw, neck, trunk, and limbs), tremor - postural, action-induced, intentional, rest tremor or swinging involvement of the proximal upper limb (wing-beating tremor). Yorio et al. (1994), have described stereotypy of toes in both feet in a patient of WD. Methods: This is a case study. Results: 26 year right handed female presents with approximate 3 months history of decline in function with slowed information processing, and dysarthirc speech. On exam she had purposeless, flexionextension movements of all fingers in both hands. They were involuntary, patterned, repetitive and rhythmic. The movements improved slightly on distraction. Occasional dystonic movements of the lips and jaw was present. Neurological exam was otherwise unremarkable. Kayser-Fleisher rings was evident on slit-lamp exam. MRI brain showed T2 hyper intensity in bilateral striatum. Laboratory investigations showed very low ceruloplasmin, high copper levels and abnormal liver function, thus confirming WD and was initiated on trientine. Conclusions: We believe, this is the first formal description of hand stereotypy in Wilson's disease. It is important and challenging to distinguish stereotypy from tremors, myoclonus, tics, dystonia, chorea and athetosis. A videotape showing patient's movements will be presented in the conference.",stereotypy;motor dysfunction;Wilson disease;Parkinson disease;tremor;patient;human;case study;tic;jaw;dystonia;speech;basal ganglion;diagnosis;information processing;chorea;copper metabolism;female;toe;forelimb;liver function;arm;diseases;laboratory;corpus striatum;myoclonus;brain;athetosis;videotape;limb;slit lamp;lip;neck;body posture;nuclear magnetic resonance imaging;copper;trientine;ceruloplasmin,"Mittal, S. O.;Ranpura, A.;Salardini, A.;Jabbari, B.",2015,June,http://dx.doi.org/10.1002/mds.26295,0,0,
1347,Bone turnover and its connection to penicillamine use in Chinese patients with Wilson disease,"Objective: The prevalence of osteoporosis is higher among patients with Wilson disease (WD) than the general public, of which the cause is still unclear. The purpose of this research is to analyze the possible causes for the high prevalence and connection between penicillamine and bone mineral density. Methods: Eight-four WD patients (44 males and 40 females) and 76 controls (27 males and 49 females) were enrolled in this study. The patients were diagnosed via mutation analysis of ATP7B. Dual-energy X-ray Analysis (DXA) was used to evaluate the bone mineral density (BMD). Serum phosphate, calcium, magnesium, parathyroid hormone, calcitonin, osteocalcin, 25-(OH)-Vitamin D as well as alkaline phosphatase were measured to evaluate the bone turnover activity. Based on the information on imaging, laboratory test and previous medical history, we analyzed the correlations between BMD, bone turnover activity and patients' age, gender, clinical manifestations and maximum dosage of penicillamine. Results: Fifty-eight patients received a DXA scan. The prevalence of osteoporosis inWD patients was 27.58% (16/58) whereas that in the controls was 19.74% (15/76). BMD, T score and Z score of lumbar vertebrae as well as BMD, Z score of hip neck were significantly lower in WD patients. 25(OH)-Vitamin D, serum phosphate, serum calcium and ALP were significantly higher inWD patients than the controls. But among patients who have received different maximum daily dosage of penicillamine, larger dose was associated with lower BMD. Age, gender and clinical manifestations did not affect BMD among WD patients. Conclusion: WD patients have a higher prevalence of osteoporosis, lower BMD and higher bone turnover activity compared with controls. The use of penicillamine is an important precipitating factor.",bone turnover;patient;human;Wilson disease;European;neurology;society;prevalence;osteoporosis;phosphate blood level;bone density;gender;female;male;epidemiology;calcium blood level;neck;hip;lumbar vertebra;medical history;laboratory test;imaging;X ray analysis;mutation;penicillamine;vitamin D;alkaline phosphatase;osteocalcin;calcitonin;parathyroid hormone,"Dong, Q. Y.;Dong, Y.;Ni, W.;Zhang, Y.;Wu, Z. Y.",2015,May,,0,0,
1348,WTX101-201: Phase 2 study of bis-choline tetrathiomolybdate in newly diagnosed wilson disease patients,"Background and Aims: Wilson Disease (WD) is a rare autosomalrecessive disorder of impaired hepatic copper excretion caused by mutations in the ATP7B gene, resulting in copper accumulation in various organs, including the liver and the brain. WTX101 (bischoline tetrathiomolybdate) is a novel de-coppering agent with a unique mechanism of action (MoA) in development for treatment of WD. WTX101 targets improved control of Cu due to the rapid formation of irreversible Cu-tetrathiomolybdate-protein complexes leading to a rapid de-coppering without mobilizing free Cu that could cause tissue toxicity, including neurological deterioration. Tetrathiomolybdate has been studied in several clinical trials in WD patients using ammonium tetrathiomolybdate. The study will evaluate if individualised BID oral dosing of WTX101 with an up-titration design in the initial de-coppering phase is safe and efficacious in lowering free copper levels (NCC, adjusted for plasma Mo concentration) as well as maintaining these lowered free copper levels using QD dosing. It will also provide data on additional free Cu endpoints, 24-hour urinary copper and neurological outcome with the UWDRS. Methods: This is a Phase 2, open-label, non-controlled, 24 week study conducted in the EU and US. An individualised WTX101 dosing regimen is administered with PPI in newly diagnosed symptomatic (neurological, stable hepatic or combined) WD patients aged 18 and older with elevated NCC levels who have been treated for <=28 days with chelation therapy or zinc therapy. Eligible subjects will receive WTX101 as out-patients at doses ranging from 30-300mg per day along with omeprazole 20mg per day. The primary endpoint is the proportion of patients who achieve normalised levels of NCC (<=2.3 muM) or reach a reduction of at least 25% in NCC. Secondary endpoints include safety and tolerability, change in and time to normalisation of NCC levels, copper endpoints (exchangeable copper, profiling of Mo/Cu/Protein tripartite complex species, and 24-hour urinary copper), hepatic status with ALT, AST, INR and bilirubin measurement, neurological assessment (UWDRS), psychiatric assessment (MINI Tracking), clinical symptom status (CGI) and QOL/PRO endpoints (EQ5D, MMAS-8, TSQM). PK of WTX101 will be measured by plasma total and free elemental Mo. Conclusions: The unique mode of action suggests thatWTX101 may be an effective treatment option for WD patients having a lower potential for neurologic deterioration while once daily dosing offers improve compliance.",liver;human;Wilson disease;patient;European;phase 2 clinical trial;deterioration;plasma;diseases;clinical trial (topic);toxicity;species;brain;titrimetry;outpatient;gene;therapy;mutation;chelation therapy;safety;excretion;international normalized ratio;choline tetrathiomolybdate;copper;tetrathiomolybdic acid;protein;bilirubin;tetrathiomolybdate ammonium;omeprazole;zinc,"Weiss, K. H.;Askari, F.;Ferenci, P.;Czlonkowska, A.;Bronstein, J.;Clark, D.;Hansson, J.;Schilsky, M.",2015,April,,0,0,
1349,Functional characterization and drug response to zinc and D-penicillamine of disease-causing ATP7B mutations in a human hepatoma cell line,"Background and Aims: In Wilson disease (WD) hepatocyte survival is significantly affected by toxic copper (Cu) overload due to mutation of the liver copper transporter ATP7B. More than 600 mutations of ATP7B are described. Copper toxicity in WD is reversed commonly by D-penicillamine (DPA) and/or zinc (Zn). The impact of the individual ATP7B mutation expressed in WD patients for efficacy of standard treatment is not known. Methods: ATP7B mutations that are frequent in Europe/USA and Asia as well as various frequent homozygous genotypes observed in India were selected. Stable cell lines were established expressing the mutations in a human hepatoma HepG2 ATP7B knockout cell line that was established recently by our group (PLoS ONE, 9: e98809, 2014). Cell survival as well as induction of apoptosis was determined in mutant cell lines following Cu exposure and Zn/DPA treatment. Results: In the mutant cell lines ATP7B protein expression varied while mRNA expression was on similar levels as compared to wild type. Co-localization studies with late endosome-lysosome marker lamp2 suggested impairment of trafficking in various mutant cell lines. Mutant cell lines showed different grades of activity to escape toxic Cu with mutation p.H1069Q displaying a moderate activity. No activity was observed for mutant cell lines encoding incomplete reading frames. Characteristic responses to treatment were observed after Zn, DPA and Zn+DPA combined treatment for individual cell lines. Overall, DPA treatment was more efficient as compared to Zn treatment. Of note, only Zn+DPA treatment could fully restore ATP7B activity as compared to ATP7B wild type. Conclusions: Individual ATP7B mutations differ in their capacity to escape toxic Cu and show genotype-specific response to treatment. The type of ATP7B mutation may modulate the efficacy of Zn and DPA treatment suggesting that current regimens might further improve using the knowledge of functional parameters exerted by ATP7B.",liver;human;mutation;hepatocellular carcinoma cell line;European;drug response;cell line;cell mutant;wild type;genotype;Wilson disease;patient;protein expression;toxicity;endosome;lysosome;Asia;parameters;India;exposure;survival;apoptosis;liver cell carcinoma;liver cell;cell survival;nucleotide sequence;penicillamine;zinc;copper;messenger RNA;marker,"Chandhok, G.;Sauer, V.;Niemietz, C.;Zibert, A.;Schmidt, H. H. J.",2015,April,,0,0,
1350,Copper-wilson's disease,"Wilson's disease was described by Kinnier Wilson over one hundred years ago. He focused on neurological aspects of the disease, however he also made critical observation that the liver was affected. He postulated that a toxic agent was responsible for both neurological and liver injury. We just know the toxin is copper and that it accumulates in toxic levels in tissues due to a defect in a specific gene ATP7B that is critical to copper transport and metabolism in liver. Injury to other organs mainly brain is secondary to copper overload in liver and increased copper level in blood. Both hepatic and neurological symptoms of the disease are very variable, from mild developing over years to rapidly progressing leading to severe disability and death. Diagnosis is crucial for WD patients. It is based on combination of clinical features, studies of copper metabolism, genetics analysis, and neuroimaging. Anticopper therapy is based either on copper chelation (d-penicillamine, trientine) or inhibition of copper absorption from gut (zinc salts). Both types of therapy seem equally effective, and choice depends on center experience, patient's preference and drug availability. Liver transplantation is performed only in cases with fulminant liver injury and progression of liver failure despite of therapy. Anticopper therapy must be lifelong. In majority of cases which are not diagnosed in the terminal stage pharmacotherapy leads to clinical improvement. It is important to screen asymptomatic siblings and children of affected patients. Early therapy prevents symptoms development. Critical for therapeutical success is patients' compliance.",neurology;European;Wilson disease;human;therapy;patient;liver;liver injury;neuroimaging;metabolism;copper metabolism;clinical feature;injury;blood;gene;diagnosis;drug bioavailability;liver transplantation;liver failure;sibling;genetics;brain;death;tissues;disability;absorption;intestine;chelation;drug therapy;neurologic disease;child;patient preference;copper;toxic substance;zinc derivative;trientine;penicillamine;toxin,"Czlonkowska, A.",2015,June,http://dx.doi.org/10.1111/ene.12813,0,0,
1351,Diagnostic value of 24h urinary copper excretion after 48h of d-penicillamine cessation in compliance assessment in Wilson's disease patients,"Background and aims: Wilson's disease (WD) is an inherited autosomal recessive disorder of copper metabolism. Treatment with anti-copper agents is effective in most cases. However, compliance is essential. Urinary copper excretion is an important parameter for diagnosis and treatment monitoring. During long-term treatment with chelating agents, a two-day interruption in treatment should result in normal values of urinary copper concentration (<50mug/dl). The aim of this study was to establish the usefulness of this method in compliance assessments in these patients. Methods: We examined consecutive patients treated with d-penicillamine (DPA) for a minimum of one year undergoing routine follow-up studies at our center. We assessed copper metabolism parameters, neurological examinations, hepatic status, and compliance. We performed 24-h urinary copper excretion analysis 48h after an interruption in chelating therapy. Results: 33 patients were enrolled. The mean treatment duration was 11.78+/-11.75 years. After 48h of DPA cessation, normalization (<50mug/24h) in copper excretion was observed in 20 (87%) of 23 compliant patients. Ten patients were non-compliant and copper excretion was above 50mug/24h in 7 (70%) of them after cessation of DPA. The specificity and sensitivity of this test was 87% and 70%, respectively. Receiver operator curve analysis found an optimal cut-off of urinary copper excretion of 62mug/dl for compliant patients. Conclusion: Measurement of 24-h urinary copper excretion after a 48-h interruption in DPA therapy in patients with WD is a reliable method for confirming patients' compliance and may be helpful for further treatment decisions.",diagnostic value;excretion;patient;human;European;neurology;Wilson disease;compliance (physical);concentration (parameters);therapy;copper metabolism;neurologic examination;parameters;follow up;normal value;long term care;monitoring;diagnosis;sensitivity and specificity;treatment duration;autosomal recessive disorder;penicillamine;copper;chelating agent,"Dziezyc, K.;Litwin, T.;Chabik, G.;Czlonkowska, A.",2015,June,http://dx.doi.org/10.1111/ene.12807,0,0,
1352,Early neurological worsening in wilson's disease patients,"Objective:The aim of our study was to analyze the frequency of early neurological worsening in WD patients, its outcome, clinical and laboratory factors which may impact it. Background: Early neurological worsening during initiation of Wilson's Disease (WD)treatment is still an unresolved therapeutic problem. Methods: We analyzed 143 symptomatic WD patients, diagnosed between 2005-2010. The early neurological deterioration group was based on worsening in Unified Wilson's Disease Score Scale (UWDRS) scored at baseline till 6 months or occurrence of new neurological symptoms. Reversibility of worsening was followedup to 24 months. Further the analysis were performed in subgroups with and without neurological worsening according to selected clinical and laboratory variables and type of anticopper therapy. Results: Early neurological worsening in 11.1 [percnt](16/143)of WD patients, only in patients with neurological signs at diagnosis.The mean time of worsening since WD treatment began was 2,3+/-1.9 months.The neurological deterioration was completely reversible in 53[percnt](8/15)and partially in 13[percnt] (2/15) patients during 9.2+/-5.2 months.The gender, age of diagnosis, disease duration, kind of WD treatment(Dpenicillamine or zinc sulphate),kind of neurological manifestations, initial copper metabolism results as well as liver functions parameters had no impact on early neurological worsening. Baseline neurological symptoms (15/69 vs.0/73;p<0.01);advance of neurological deficits scored in UWDRS part II and III(p<0.01); the occurrence of brain magnetic resonance imaging (MRI) changes due to WD in thalamus(p<0.01)and brain stem(p<0.01); the concomitant treatment with drugs potentially modulating the action of dopamine (p<0.05),were the main predictors of early neurological deterioration in WD patients. Conclusions: Neurological worsening at the beginning of the anticopper therapy in WD patients occur in patients with severe initial neurological manifestation, advanced brain injury and may be also provoked by concomitant treatment, but it is not associated with the type of anticopper therapy.",American;patient;neurology;human;Wilson disease;therapy;deterioration;neurologic disease;laboratory;parameters;brain injury;liver function;copper metabolism;brain stem;thalamus;disease duration;nuclear magnetic resonance imaging;brain;diagnosis;gender;dopamine;zinc sulfate,"Czlonkowska, A.;Litwin, T.;Karlinski, M.;Dziezyc, K.",2015,,,0,1,
1353,Zinc therapy reverses neurodegeneration in wilson's disease patients with parkinsonism,"Objective: To evaluate how effective zinc therapy can reverse parkinsonism in Wilson's disease patients who were initially treated with penicillamine. Background: For years, the treatment of Wilson's disease has been aiming at stimulating the excretion of accumulated copper by chelating agents. The dilemma arises when patients paradoxically deteriorate, which is because chelators increase free copper levels. Conversely, zinc therapy normalizes the raised serum and urine free copper by inducing metallothionein production. Methods: In a retrospective observational study on four Wilson's disease patients with severe parkinsonism being initially treated with penicillamine with or without zinc, we compared the subjective and objective clinical improvement before and one year after shifting to zinc monotherapy. Global Assessment Scale (GAS) was used for clinical evaluations. Global disability were measured in four domains: liver, cognition and behavior, motor, and osseomuscular, and the neurological dysfunction were assessed in 14 main categories. Results: Three of the four patients who had been deteriorated on penicillamine (0.5-1 g/d), have improved significantly to a normal biochemical and clinical state on zinc (150 mg/d). The fourth patient on 250 mg/d penicillamine plus 200 mg/d zinc slightly improved in lower extremities after one month, while she considerably improved to a symptom-free state in the following months on zinc monotherapy. Their global disability improved by about 73%, and neurological assessments revealed a 100% amelioration. Conclusions: The results suggest zinc monotherapy as the safe and promising treatment for copper intoxication, and support normalizing the increased serum and urine copper values as a rational therapeutic strategy.",therapy;nerve degeneration;parkinsonism;patient;human;Wilson disease;Parkinson disease;monotherapy;disability;urine;serum;health status;cognition;liver;excretion;clinical evaluation;observational study;intoxication;leg;zinc;copper;penicillamine;chelating agent;metallothionein,"Avan, A.;Azarpazhooh, M. R.;Hoogenraad, T. U.",2015,March,http://dx.doi.org/10.1159/000381736,0,1,
1354,Successful initial zinc therapy in wilson's disease with acute liver failure and copper intoxication: Wonder drug exists,"Objectives: To evaluate initial zinc monotherapy on copper levels and hepatic improvement. Background: Accumulation of copper in brain and liver is regarded as the cause of Wilson's disease. However, there is evidence suggesting the free copper intoxication as the origin. Methods: Retrospectively, a 10-year-old girl with Wilson's disease presented with diffuse jaundice, acute liver failure, hemolytic anemia, and high urine copper, liver function and copper values with a positive family history was evaluated before and after initial zinc monotherapy. The patient was treated with 125 mg elemental zinc per day, and liver transplantation was considered in case of nonresponsiveness. Results: The patient improved biochemically and clinically in 10 days after zinc therapy, which were in accordance with 86% urinary copper decrease. The revised Wilson's disease prognostic index improved from 13 to 5, and the patient was removed from the transplant list. After 2, 4, 8 weeks on zinc therapy, AST, ALT, bilirubin, urine copper showed constant improvements of up to 62, -26, 82, 77%, respectively by the eighth week,. The results of the second 8-week period indicated a further decrease of 25, 41, 48, 86, respectively, and 33% for serum free copper, compared to the previous results. No side effects, or clinical deterioration has been observed. Conclusions: The results suggest zinc therapy as a promising, fast-acting, safe and affordable choice for the treatment of copper intoxication in Wilson's disease with acute liver failure. It also supports the hypothesis of normalization of raised serum free copper as a rational targeted-therapeutic strategy.",acute liver failure;intoxication;therapy;Parkinson disease;Wilson disease;human;patient;serum;monotherapy;urine;girl;side effect;female;transplantation;liver transplantation;liver;deterioration;liver function;brain;family history;hemolytic anemia;hypothesis;jaundice;zinc;copper;bilirubin,"Avan, A.;Kianifar, H. R.;Hoogenraad, T. U.",2015,March,http://dx.doi.org/10.1159/000381736,0,0,
1355,Copper chelation efficacy of D-penicillamine nanoparticles in experimental rat model for non-wilsonian brain copper toxicosis,"Objective: D-penicillamine is unable to mitigate the brain copper overload and neurological manifestations in Alzheimer's/Wilson's disease patients. The aim of this study was to assess the therapeutic efficacy of orally administered D-penicillamine loaded nanoparticles to that of conventional D-penicillamine for 90 days in Wistar rat model for non-Wilsonian brain copper toxicosis. Methods: High performance liquid chromatography, atomic absorption spectrophotometry, neurobehavioral and histopathological studies, and nanoparticles preparation/physicochemical characterization were carried out. Results: D-penicillamine nanoparticles exhibited mean 274.09 nm size and less than 29.32% of D-penicillamine release under in vitro conditions. Pharmacokinetics studies showed augmented levels of D-penicillamine in brain of nanoparticles based D-penicillamine delivery group compared to conventional D-penicillamine delivery group. Conventional and nanoparticles based D-penicillamine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary copper levels, and acetylcholinesterase activity in rat model of copper toxicosis. Conventional D-penicillamine therapy resulted in negative rhodanine staining of liver and brain sections corroborated by 60.1%, and16.4% reduction in hepatic and brain copper content, respectively compared to non-treated copper-intoxicated group. However, liver and brain sections of nanoparticles based D-penicillamine therapy group demonstrated grade 1 copper and no copper depositions substantiated by 47.2% and 32.8% reduction in hepatic and brain copper content, respectively in comparison to non-treated copper-intoxicated group. Conclusions: Taken together, the present study reveals the first in vivo evidence for therapeutic efficacy of nanoparticles based D-penicillamine therapy in chelating more brain copper and alleviating neurological deficits even at half the dose as given in conventional D-penicillamine therapy.",rat;chelation;rat model;experimental rat;brain;intoxication;Parkinson disease;therapy;liver;in vitro study;atomic absorption spectrometry;implantable cardiac monitor;high performance liquid chromatography;Wistar rat;histopathology;pharmacokinetics;human;staining;memory;patient;Wilson disease;copper;nanoparticle;penicillamine;rhodanine;acetylcholinesterase,"Pal, A.;Vasishta, R. K.;Thapa, B. R.;Prasad, R.",2015,March,http://dx.doi.org/10.1159/000381736,0,0,
1356,Successful liver transplantation for Wilson's disease as a rare cause of hepatic failure after SCT in a child with Fanconi aplastic anemia,"Introduction: After allogeneic stem cell transplantation liver toxicity may be due to several reasons, such as drug toxicity, graft versus host disease, hepatic veno-oclusive disease. However, other rare causes should be in mind. We present a child developing liver failure after allo-SCT and then diagnosed Wilson's disease. The patient was successfully treated with repeated plasmapheresis for acute hepatic failure and then transplanted cadaveric liver. Materials (or patients) and methods: 13-year-old male patient was diagnosed as Fanconi aplastic anemia and stem cell transplantation was performed from HLA full matched sister. Reduced conditioning regimen was consisted of fludarabine plus cyclophosphamide. Liver enzymes and bilirubin levels were moderately elevated after engraftment. Hepatitis markers were negative. We thought the hepatic toxicity to be due to conditioning regimen. Abdominal acid did not developed. Total bilirubin levels were 10-15mg / dl during the first three months and remained relatively stable around. Direct bilirubin levels began to rise in the fourth month of the patient, coagulation tests were became abnormal. Percutaneous liver biopsy was taken. In the preliminary report of biopsy, toxic hepatitis was considered. All drugs including cyclosporine A were stopped except trimethoprim sulphamethoxazole. Bilirubin values rose during this period. Total bilirubin was 35.7 mg/dL, and direct bilirubin 26.7 mg/dL, ammonia 194.6 mcg/dl, and ceruloplasmin 47.1 mg/dl. Patients were considered going to hepatic coma and started to receive therapeutic plasmapheresis. The total seven times plasmapheresis were made. The first five plasmapheresis were made with fresh frozen plasma. Allergic reactions occurred in the last plasmapheresis. One week later, two plasmapheresis were made with albumin. Results: Liver biopsy was reported as toxic hepatitis and copper accumulation. The copper level of 24- hour urine was high levels. The patient was diagnosed as Wilson's disease. D-penicillamine and zinc therapy was started. Cadaveric liver transplantation was performed one month later. Two years after stem cell transplantation the patient is disease free, with complete donor chimerism in bone marrow and stable hepatic graft function with immunosuppressive therapy. Conclusion: As a result, in hepatic toxicity after allo-SCT, Wilson's disease should be in mind. The patients with autosomal recessive diseases such as Fanconi aplastic anemia may be have another autosomal recessive disease. For this reason, a detailed family medical history should be taken.",liver transplantation;child;liver failure;European;Fanconi anemia;human;society;blood;bone marrow;transplantation;Wilson disease;patient;plasmapheresis;toxic hepatitis;toxicity;stem cell transplantation;liver biopsy;conditioning;autosomal recessive disorder;biopsy;liver toxicity;allogeneic stem cell transplantation;liver;hepatitis;liver graft;acute liver failure;blood clotting test;donor;therapy;engraftment;urine;allergic reaction;hepatic coma;male;graft versus host reaction;drug toxicity;chimera;immunosuppressive treatment;family history;bilirubin;copper;bilirubin glucuronide;acid;marker;zinc;penicillamine;liver enzyme;cyclophosphamide;fresh frozen plasma;albumin;fludarabine;ceruloplasmin;ammonia;cotrimoxazole;cyclosporin A,"Albayrak, C.;Albayrak, D.;Kalayci, A. G.;Bicakci, A.;Elli, M.",2015,March,http://dx.doi.org/10.1038/bmt.2015.37,0,0,
1357,Molecular genetic diagnosis of PFIC 3 overlapping presentation with Wilson disease and response to treatment,"Case: The patient presented age 15 years with fatigue and findings of splenomegaly and mild thrombocytopenia. Further testing included 24 h urine copper [> 100 mcg], no Kayser-Fleischer rings, normal ceruloplasmin level and no mutations of ATP7B. Liver biopsy showed chronic hepatitis, focal bridging fibrosis, moderate bile duct proliferation and a markedly elevated hepatic copper content (1471 mug/g), suggesting WD. She was started on zinc therapy, but was switched to trientine due to gastrointestinal side effects. Though treated with trientine for > 12 months, her transaminase levels didn'timprove and urine copper remained elevated. Further evaluation for another possible etiology revealed increased bile acids. A trial of ursodeoxycholic acid (UDCA) was initiated for PFIC3. ABCB4 gene sequencing showed heterozygous c.984T > G (p.Y328*) mutation consistent with a diagnosis of PFIC3. Trientine was discontinued and she was continued on UDCA. With UDCA treatment, transaminases decreased but didn't normalize (Table). Liver biopsy was repeated after 4 months of therapy and showed hepatic copper content dramatically decreased to 135 mug/g dry weight liver. After 10 months liver indices remained mildly abnormal but synthetic function was stable. Conclusions: Hepatic copper accumulation can be seen in cholestatic disorders such as PFIC3 at levels above the diagnostic threshold for WD, and therefore the diagnosis of PFIC3 should be considered in patients with elevated hepatic copper without clear features of WD and who fail to adequately respond to treatment. UDCA ameliorates cholestasis in PFIC3 and we show for the first time a reduction in hepatic copper in response to treatment.",Wilson disease;Asian;liver;diagnosis;liver biopsy;urine;human;patient;therapy;mutation;fibrosis;thrombocytopenia;chronic hepatitis;splenomegaly;bile duct;fatigue;etiology;gastrointestinal symptom;gene sequence;dry weight;diseases;cholestasis;copper;trientine;aminotransferase;ursodeoxycholic acid;bile acid;ceruloplasmin;zinc,"Boga, S.;Jain, D.;Schilsky, M.",2015,March,http://dx.doi.org/10.1007/s12072-015-9609-1,0,0,
1358,Colitis during trientine therapy for wilson disease a case report,"Case: A 40 year old female patient with recent diagnosis of Wilson disease (WD) with predominant neuropsychiatric symptoms was started on triethylene tetramine dihydrochloride (trientine) 250 mg three times daily and developed bloody diarrhea. Trientine was discontinued, and a colonoscopy showed active ileitis and severe colitis of indeterminate nature. She was started on prednisone, and had acute worsening of her neuropsychiatric symptoms and was referred to us with the pre-diagnosis of steroid psychosis. Zinc therapy was initiated for her WD and the prednisone was stopped. Clinical symptoms of colitis improved and sigmoidoscopy showed resolution of her colitis. Due to persistent neuropsychiatric symptoms, trientine was restarted. She again developed multiple bloody bowel movements so trientine was discontinued. Evaluation for other causes of colitis was negative for infection and markers for IBD. A repeat colonoscopy at this time showed active colitis and proctitis. Histology showed extensive inflammation with cryptitis, crypt abscess formation and ulcerations, suggestive of a medication-induced colitis. The patient was restarted on zinc therapy for her WD and had resolution of symptoms of colitis without recurrence. All of her neurological symptoms improved and resolved over a longer period of time. She had stable liver function while on zinc maintenance therapy. Conclusion: Chelation therapy is an integral part of the initial therapy of symptomatic patients with WD, however patients must be monitored appropriately for side effects. Colitis is a rare side effect of trientine and zinc is an alternative therapy for patients with WD with side effects due to chelation therapy.",colitis;human;therapy;Wilson disease;case report;Asian;liver;patient;side effect;colonoscopy;chelation therapy;diagnosis;alternative medicine;ileitis;maintenance therapy;neurologic disease;ulcer;abscess;inflammation;proctitis;bloody diarrhea;infection;histology;intestine;sigmoidoscopy;drug therapy;liver function;psychosis;female;trientine;zinc;prednisone;marker;steroid,"Boga, S.;Jain, D.;Schilsky, M.",2015,March,http://dx.doi.org/10.1007/s12072-015-9609-1,0,0,
1359,Wilson disease with hepatic presentation in an 8 month old boy,"Wilson disease is an autosomal recessive disorder of copper deposition that can cause fatal neurological and hepatic disease if not diagnosed and treate. The youngest child with normal liver function reported so far is an 8-month-old Japanese boy with low ceruloplasmin levels. In terms of liver function abnormality, the youngest child ever reported so far is a 9-month-old Korean boy with elevated aminotransferase confirmed by genetic testing. We report an 8-monthold Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7B gene detected two heterozygous mutations (c.3809A>G/p. A874 V and c.2621C>T/p.N1270S) that have been reported to cause WD in the Wilson Disease Mutation Database. Parents screened for the disease causing mutations. Father was heterozygous for the mutation of c.3809A>G/p.N1270S, and mother was heterozygous for c.2621C>T/p.A874 V. Elevated serum aminotransferase in this infant was refractory, but persistent normalization was achieved with zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.",Wilson disease;boy;male;human;Asian;liver;mutation;hypertransaminasemia;child;Japanese (citizen);liver function;genetic analysis;ceruloplasmin blood level;liver disease;diagnosis;genetic screening;hope;gene;therapy;infant;aminotransferase blood level;mother;female;father;parent;data base;patient;pediatrician;Japanese (people);autosomal recessive disorder;copper;aminotransferase;ceruloplasmin;zinc,"Abuduxikuer, K.;Wang, J. S.",2015,March,http://dx.doi.org/10.1007/s12072-015-9609-1,0,0,
1360,Gabapentin can improve dystonia in confirmed wilson disease,,adult;Barthel index;bradykinesia;case report;ceruloplasmin blood level;cervical dystonia;clinical examination;disease course;disease severity;drug efficacy;drug treatment failure;drug withdrawal;dysarthria;dyskinesia;dysphagia;dystonia/dt [Drug Therapy];esophagus varices;female;gait disorder;gene mutation;generalized dystonia;hand tremor;hepatitis;human;hypersalivation;Mini Mental State Examination;nuclear magnetic resonance imaging;opisthotonus;palliative therapy;priority journal;segmental dystonia;short survey;slit lamp;thrombocytopenia/si [Side Effect];treatment duration;urine level;Wilson disease;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];diazepam;gabapentin/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];trihexyphenidyl,"Lerose, M.;Fabio, R. D.;Serrao, M.;Loudianos, G.;Pierelli, F.;Casali, C.",2014,01 Mar,http://dx.doi.org/10.1017/S0317167100016759,0,0,
1361,Lead toxicity in battery workers,"Lead poisoning is a medical condition caused by increased levels of lead in the body. Routes of exposure include contaminated air, water, soil, food and consumer products. Occupational exposure is the main cause of lead poisoning in the adults. Two cases of occupational lead poisoning in adult battery workers are hereby presented. Both male patients had initial non-specific symptoms of intermittent abdominal pain, fatigue and headache for 6 - 8 years. Later on, they developed psychosis, slurred speech, tremors of hands and initially underwent treatment for Parkinsonism and Wilson's disease because of clinical misdiagnosis. They were diagnosed with lead poisoning later and were treated successfully with lead chelator (CaNa<inf>2</inf> EDTA).",Abdominal pain;Lead chelate calcium disodium edetate;Lead poisoning;Occupational exposure;Tremors;adult;aggression;anemia;arthralgia;article;battery industry;battery worker;bone marrow examination;burning sensation;case report;cell hyperplasia;chelation therapy;computer assisted tomography;creatinine blood level;diagnostic error;diarrhea;fatigue;hand tremor;headache;human;industrial worker;irritability;irritable colon;lead blood level;lead poisoning/di [Diagnosis];lead poisoning/dt [Drug Therapy];lead poisoning/et [Etiology];lead poisoning/th [Therapy];loss of appetite;malaise;male;multiple cycle treatment;neurologic examination;occupational disease/di [Diagnosis];occupational disease/dt [Drug Therapy];occupational disease/et [Etiology];occupational disease/th [Therapy];parkinsonism/di [Diagnosis];psychosis/dt [Drug Therapy];slurred speech;treatment duration;urea blood level;vertigo;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];creatinine/ec [Endogenous Compound];edetate calcium disodium/dt [Drug Therapy];edetate calcium disodium/iv [Intravenous Drug Administration];edetic acid/dt [Drug Therapy];edetic acid/iv [Intravenous Drug Administration];lead/to [Drug Toxicity];lead/ec [Endogenous Compound];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];urea/ec [Endogenous Compound],"Qasim, S. F.;Baloch, M.",2014,,,0,0,
1362,Simultaneous monitoring of cerebral metal accumulation in an experimental model of Wilson's disease by laser ablation inductively coupled plasma mass spectrometry,"Background: Neuropsychiatric affection involving extrapyramidal symptoms is a frequent component of Wilson's disease (WD). WD is caused by a genetic defect of the copper (Cu) efflux pump ATPase7B. Mouse strains with natural or engineered transgenic defects of the Atp7b gene have served as model of WD. These show a gradual accumulation and concentration of Cu in liver, kidneys, and brain. However, still little is known about the regional distribution of Cu inside the brain, its influence on other metals and subsequent pathophysiological mechanisms. We have applied laser ablation inductively coupled plasma mass spectrometry and performed comparative metal bio-imaging in brain sections of wild type and Atp7b null mice in the age range of 11-24 months. Messenger RNA and protein expression of a panel of inflammatory markers were assessed using RT-PCR and Western blots of brain homogenates. Results: We could confirm Cu accumulation in brain parenchyma by a factor of two in WD (5.5 mug g<sup>-1</sup> in the cortex) vs. controls (2.7 mug g<sup>-1</sup>) that was already fully established at 11 months. In the periventricular regions (PVR) known as structures of prominent Cu content, Cu was reduced in turn by a factor of 3. This corroborates the view of the PVR as efflux compartments with active transport of Cu into the cerebrospinal fluid. Furthermore, the gradient of Cu increasing downstream the PVR was relieved. Otherwise the architecture of Cu distribution was essentially maintained. Zinc (Zn) was increased by up to 40% especially in regions of high Cu but not in typical Zn accumulator regions, a side effect due to the fact that Zn is to some degree a substrate of Cu-ATPases. The concentrations of iron (Fe) and manganese (Mn) were constant throughout all regions assessed. Inflammatory markers TNF-alpha, TIMP-1 and the capillary proliferation marker alpha-SMA were increased by a factor of 2-3 in WD. Conclusions: This study confirmed stable cerebral Cu accumulation in parenchyma and discovered reduced Cu in cerebrospinal fluid in Atp7b null mice underlining the diagnostic value of micro-local analytical techniques. Copyright © 2014 Boaru et al.; licensee BioMed Central Ltd.",ATPase7B;Bio-imaging;Copper;la-icp-ms;Wilson's disease;active transport;animal experiment;animal model;animal tissue;article;brain homogenate;brain region;capillary proliferation;cerebrospinal fluid;controlled study;laser surgery;mass spectrometry;mouse;neuroimaging;nonhuman;periventricular region;protein expression;reverse transcription polymerase chain reaction;Western blotting;wild type;Wilson disease/et [Etiology];alpha smooth muscle actin/ec [Endogenous Compound];ferric ion;manganese;messenger RNA/ec [Endogenous Compound];tissue inhibitor of metalloproteinase 1/ec [Endogenous Compound];tumor necrosis factor alpha/ec [Endogenous Compound];zinc ion,"Boaru, S. G.;Merle, U.;Uerlings, R.;Zimmermann, A.;Weiskirchen, S.;Matusch, A.;Stremmel, W.;Weiskirchen, R.",2014,August 20,http://dx.doi.org/10.1186/1471-2202-15-98,0,0,
1363,Genotype-phenotype correlations in a mountain population community with high prevalence of wilson's disease: Genetic and cinical homogeneity,"Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1:1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18+/-1 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities. © 2014 Cocos et al.",adolescent;adult;article;asymptomatic disease;ATP7B gene;child;clinical article;clinical assessment;clinical feature;community sample;controlled study;cultural anthropology;dysarthria;dysphagia;dystonia;environmental factor;family size;family study;female;gene sequence;genetic screening;genotype phenotype correlation;heredity;heterozygote;human;male;nucleotide sequence;onset age;population genetics;population research;preschool child;prevalence;school child;single nucleotide polymorphism;symptom;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];young adult;cysteine/ec [Endogenous Compound];glutamine/ec [Endogenous Compound];histidine/ec [Endogenous Compound];methionine/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Cocos, R.;Sendroiu, A.;Schipor, S.;Bohiltea, L. C.;Sendroiu, I.;Raicu, F.",2014,04 Jun,http://dx.doi.org/10.1371/journal.pone.0098520,0,0,
1364,Neurologic manifestations of acute and chronic liver disease,"PURPOSE OF REVIEW: This article summarizes the most common neurologic sequelae of acute and chronic liver failure, liver transplantation, and other treatments for liver disease, and outlines the pathogenesis, neurologic manifestations, and treatment of Wilson disease. RECENT FINDINGS: The neurologic manifestations of liver disease are caused by the liver's failure to detoxify active compounds that have deleterious effects on the central and peripheral nervous systems. In addition, treatments for liver disease such as liver transplantation, transjugular intrahepatic portosystemic shunt, and antiviral medications can also be neurotoxic. Wilson disease affects the liver and nervous system simultaneously and may often initially be diagnosed by a neurologist; treatment options have evolved over recent years. SUMMARY: Acute and chronic liver diseases are encountered commonly in the general population. Neurologic dysfunction will eventually affect a significant number of these individuals, especially if the disease progresses to liver failure. Early recognition of these neurologic manifestations can lead to more effective management of these patients. Copyright © American Academy of Neurology.",acquired hepatocerebral degeneration;acute liver disease/dt [Drug Therapy];acute liver disease/su [Surgery];acute liver failure;antiviral therapy;central nervous system;chronic liver disease/dt [Drug Therapy];chronic liver disease/su [Surgery];chronic liver failure;hepatic encephalopathy;hepatic myelopathy;hepatic neuropathy;hepatitis C;human;liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver transplantation;neurologic disease;neurologist;peripheral nervous system;peripheral neuropathy;review;slit lamp;spinal cord disease;transjugular intrahepatic portosystemic shunt;Wilson disease;antivirus agent/dt [Drug Therapy];penicillamine,"White, H.",2014,June,http://dx.doi.org/10.1212/01.CON.0000450973.84075.a7,0,0,
1365,"Case 30-2014: A 29-year-old man with diarrhea, nausea, and weight loss",,abdominal discomfort;adult;article;case report;defecation urgency;diarrhea;differential diagnosis;drug dose increase;dry skin;echography;esophagogastroduodenoscopy;esophagus varices/di [Diagnosis];fatigue;hepatitis C;human;human tissue;liver biopsy;liver cirrhosis;liver fibrosis;loose feces;male;nausea;priority journal;splenomegaly;weight reduction;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];trientine/dt [Drug Therapy],"Hunt, D. P.;Sahani, D. V.;Corey, K. E.;Masia, R.",2014,25 Sep,http://dx.doi.org/10.1056/NEJMcpc1405218,0,0,
1366,Erratum: Treatment with d-penicillamine or zinc sulphate affects copper metabolism and improves but not normalizes antioxidant capacity parameters in Wilson disease (Biometals DOI: 10.1007/s10534-013-9694-3),,erratum;error,"Gromadzka, G.;Karpinska, A.;Przybylkowski, A.;Litwin, T.;Wierzchowska-Ciok, A.;Dziezyc, K.;Chabik, G.;Czlonkowska, A.",2014,February,http://dx.doi.org/10.1007/s10534-014-9706-y,0,0,
1367,Long term results of liver transplantation for Wilson's disease: Experience in France,"Background & Aims Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long-term outcome of WD patients following LT. Methods The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18-66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7-53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). Results Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. Conclusions Liver failure associated with WD is a rare indication for LT (<1%), which achieves an excellent long-term outcome, including renal function. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",Abbreviations;acute liver failure;alf;blood pressure;bmi;body mass index;bp;calcineurin-inhibitor;chronic liver disease;cld;cni;fhf;fulminant hepatic failure;hat;hcc;hepatic artery thrombosis;hepatocellular carcinoma;liver transplantation;lt;mmf;mycophenolate mofetil;n.a.;not available;pnf;primary non function;sfhf;subfulminant hepatic failure;wd;Wilson's disease;acute graft rejection/co [Complication];acute liver failure/dt [Drug Therapy];acute liver failure/su [Surgery];adolescent;adult;adult disease/dt [Drug Therapy];adult disease/pc [Prevention];adult disease/su [Surgery];aged;article;chelation therapy;child;childhood disease/dt [Drug Therapy];childhood disease/pc [Prevention];childhood disease/su [Surgery];chronic graft rejection/co [Complication];chronic graft rejection/su [Surgery];controlled study;corticosteroid therapy;drug blood level;drug dose reduction;drug substitution;drug withdrawal;female;follow up;France;glomerulus filtration rate;graft survival;hepatic artery thrombosis/co [Complication];hepatic artery thrombosis/su [Surgery];hepatitis/su [Surgery];human;human tissue;hyperacute graft rejection/co [Complication];hyperacute graft rejection/su [Surgery];immunosuppressive treatment;kidney failure;liver biopsy;liver cirrhosis/su [Surgery];liver graft rejection/co [Complication];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver graft rejection/su [Surgery];maintenance drug dose;major clinical study;male;middle aged;monotherapy;neurologic disease/su [Surgery];outcome assessment;patient compliance;pediatric surgery;preschool child;priority journal;prognosis;retransplantation;retrospective study;school child;survival rate;unspecified side effect/si [Side Effect];Wilson disease/su [Surgery];young adult;azathioprine/dt [Drug Therapy];cyclosporin/cb [Drug Combination];cyclosporin/cr [Drug Concentration];cyclosporin/dt [Drug Therapy];cyclosporin/po [Oral Drug Administration];cyclosporin A;everolimus/dt [Drug Therapy];methylprednisolone/cb [Drug Combination];methylprednisolone/dt [Drug Therapy];methylprednisolone/iv [Intravenous Drug Administration];mycophenolic acid 2 morpholinoethyl ester/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];rapamycin/dt [Drug Therapy];tacrolimus/cb [Drug Combination];tacrolimus/cr [Drug Concentration];tacrolimus/dt [Drug Therapy];tacrolimus/po [Oral Drug Administration];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Guillaud, O.;Dumortier, J.;Sobesky, R.;Debray, D.;Wolf, P.;Vanlemmens, C.;Durand, F.;Calmus, Y.;Duvoux, C.;Dharancy, S.;Kamar, N.;Boudjema, K.;Bernard, P. H.;Pageaux, G. P.;Salame, E.;Gugenheim, J.;Lachaux, A.;Habes, D.;Radenne, S.;Hardwigsen, J.;Chazouilleres, O.;Trocello, J. M.;Woimant, F.;Ichai, P.;Branchereau, S.;Soubrane, O.;Castaing, D.;Jacquemin, E.;Samuel, D.;Duclos-Vallee, J. C.",2014,March,http://dx.doi.org/10.1016/j.jhep.2013.10.025,0,0,
1368,Punched holes in globus pallidi: A novel neuroimaging finding in wilson disease,,brain disease;case report;ceruloplasmin blood level;child;computer assisted tomography;globus pallidus;human;image display;male;neuroimaging;note;nuclear magnetic resonance imaging;priority journal;punched hole;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;risperidone/dt [Drug Therapy];tetrathiomolybdic acid;trientine;zinc,"Kamate, M.;Hattiholi, V.",2014,March,http://dx.doi.org/10.1016/j.pediatrneurol.2013.09.011,0,0,
1369,Alzheimer's disease causation by copper toxicity and treatment with zinc,"Evidence will be presented that the Alzheimer's disease (AD) epidemic is new, the disease being very rare in the 1900s. The incidence is increasing rapidly, but only in developed countries. We postulate that the new emerging environmental factor partially causal of the AD epidemic is ingestion of inorganic copper from drinking water and taking supplement pills, along with a high fat diet. Inorganic copper can be partially directly absorbed and elevate the serum free copper pool. The Squitti group has shown that serum free copper is elevated in AD, correlates with cognition, and predicts cognition loss. Thus, our inorganic copper hypothesis fits well with the Squitti group data. We have also shown that AD patients are zinc deficient compared to age-matched controls. Because zinc is a neuronal protective factor, we postulate that zinc deficiency may also be partially causative of AD. We carried out a small 6 month double blind study of a new zinc formulation and found that in patients age 70 and over, it protected against cognition loss. Zinc therapy also significantly reduced serum free copper in AD patients, so efficacy may come from restoring normal zinc levels, or from lowering serum free copper, or from both. © 2014 Brewer.",Alzheimer's disease;Cognition;Inorganic copper;Serum free copper;Zinc deficiency;age;Alzheimer disease/et [Etiology];article;Clinical Dementia Rating;copper blood level;copper deficiency;developed country;diet supplementation;epidemic;fat intake;gene control;human;lipid diet;Mini Mental State Examination;nonhuman;pathology;pill;prevalence;risk factor;Wilson disease;zinc blood level;copper/to [Drug Toxicity];drinking water;zinc,"Brewer, G. J.",2014,,http://dx.doi.org/10.3389/fnagi.2014.00092,0,0,
1370,"Erratum: Zinc mono-therapy in pre-symptomatic chinese children with wilson disease: A single center, retrospective study (PLoS ONE 9:3 (e92491) DOI: 10.1371/journal.pone.0092491)",,erratum;error,Anonymous,2014,10 Apr,http://dx.doi.org/10.1371/journal.pone.0092491,0,0,
1371,A case study on wilson disease,"Wilson disease, also known as hepatolenticular degeneration, is a disorder in the liver that results in the improper metabolism of copper, which leads to accumulation of excessive amounts of this vital trace element in the liver, brain, eyes, and other organs. Although copper is essential for normal physiologic function, it can become toxic and life-threatening when too much is present within critical organs, especially the liver and the brain. There is no cure for Wilson disease, and patients affected with this disorder face a lifetime of treatment. Fortunately, the disease is very treatable if diagnosed before significant damage to the liver or brain occurs. This article presents a case study on Wilson disease and the role of sonography in helping diagnose and monitor patients with this condition. © The Author(s) 2013.",copper;hepatolenticular degeneration;liver;sonography;Wilson disease;abdominal discomfort/si [Side Effect];adult;article;biliary tract surgery;case report;chelation therapy;copper blood level;echograph;echography;fatty liver/di [Diagnosis];human;incidental finding;male;nausea/si [Side Effect];patient compliance;priority journal;ultrasound transducer;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Mills, B.;Baker, A. L.;Whitney, E. C.",2014,January-February,http://dx.doi.org/10.1177/8756479313517765,0,0,
1372,Zinc-induced gastric ulcer: Case report on two patients with wilson's disease,"Zinc has been developed as an effective and nontoxic therapy in Wilson's disease. Zinc salts are generally well tolerated. Mild gastrointestinal discomfort is the major observed side effect and may be dependent on the zinc salt employed. Here, we report two Wilson's disease patients who presented with severe gastric ulceration few months after beginning treatment with zinc acetate 50 mg three times a day. Our patients were not taking any ulcerogenic drugs and had no evidence of Helicobacter pylori infection. In both patients, zinc acetate was replaced by penicillamine and proton pump inhibitor therapy was initiated with complete resolution of gastrointestinal symptoms. To our knowledge, this is the first report of zinc acetate-induced gastric ulceration, which should be looked for in Wilson's disease patients who develop abdominal discomfort while on this drug.",Gastric ulcer;Wilson's disease;Zinc acetate;abdominal discomfort/si [Side Effect];absence of side effects/si [Side Effect];adult;article;case report;drug withdrawal;echography;epigastric pain/si [Side Effect];esophagogastroduodenoscopy;female;gastrointestinal endoscopy;genetic analysis;human;human tissue;immunohistochemistry;loss of appetite/si [Side Effect];male;nuclear magnetic resonance imaging;patient compliance;single drug dose;stomach biopsy;stomach ulcer/si [Side Effect];thrombocyte count;thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];esomeprazole/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy],"Mirjana, K.;Srdjana, T.;Dora, G.;Tomislav, B.;Katja, G. R.",2014,,http://dx.doi.org/10.5530/ami.2014.2.12,0,0,
1373,Myocardial integrated ultrasonic backscatter for early detection of cardiac involvement in patients with Wilson disease,"Background/Aims: Videodensitometry is a feasible noninvasive ultrasound tissue characterization method allowing early detection of myocardial changes. This study aimed to investigate ultrasonic backscatter properties of the myocardium in Wilson disease patients. bMaterials and Methods: We compared cardiologically asymptomatic Wilson disease patients (W group) (n=18) bwith age-matched (26.7+/-9.6 years) healthy controls (C group) (n=15). Diagnosis of Wilson disease was made on the basis of clinical manifestations, family history, and laboratory findings and confirmed by liver biopsy. Transthoracic echocardiographic quantitative texture analysis was performed on data from the septum and left ventricular posterior wall, and mean gray level (MGL) histograms at end-diastole (d) and end-systole (s) were obtained after background correction (c). Cyclic variation index (CVI) was calculated using the formula [(cMGLd - cMGLs) / cMGLd] x100. bResults: There were no significant differences in sex, age, body mass index, heart rate or blood pressure, and conventional echocardiographic parameters between the 2 groups. The cMGLs value of the posterior wall was higher in the W group than in the C group (30.9+/-2.6 vs. 22.2+/-2.7, p=0.033). The W group had a significantly lower CVI of the septum than did the C group (-22+/-4.4% vs. 43.4 +/-12.9%, p<0.001), and there was no significant difference in the CVI of the posterior wall (-67.0+/-15.9% vs. 41.7+/-18.6%, p=0.32). bConclusion: Abnormalities in two-dimensional echocardiographic grey-level distributions were present in Wilson disease patients. These videodensitometric myocardial alterations were significantly lower in Wilson disease patients than in the controls, and this probably represents an early stage of cardiac involvement. © Copyright 2014 by The Turkish Society of Gastroenterology.",Echocardiography;Heart;Tissue Doppler;Videodensitometry;Wilson disease;adolescent;adult;alanine aminotransferase blood level;albumin blood level;article;aspartate aminotransferase blood level;blood pressure;body mass;cardiovascular parameters;ceruloplasmin blood level;chelation therapy;child;cholesterol blood level;clinical article;controlled study;copper blood level;copper chelation therapy;cyclic variation index;disease duration;Doppler echocardiography;female;globulin blood level;heart left ventricle ejection fraction;heart left ventricle mass;heart muscle;heart rate;heart ventricle enddiastolic pressure;heart ventricle function;hemoglobin blood level;human;liver biopsy;male;thrombocyte count;tissue Doppler imaging;transthoracic echocardiography;triacylglycerol blood level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin glucuronide/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];cholesterol/ec [Endogenous Compound];globulin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];high density lipoprotein/ec [Endogenous Compound];low density lipoprotein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];triacylglycerol/ec [Endogenous Compound];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];zinc sulfate/ec [Endogenous Compound],"Arat, N.;Kacar, S.;Golbasi, Z.;Akdotan, M.;Kuran, S.",2014,,http://dx.doi.org/10.5152/tjg.2014.5949,0,0,
1374,"Osteoporosis and fractures in liver disease: Relevance, pathogenesis and therapeutic implications","It is being increasingly recognized that patients with liver disease develop bone loss that can be severe enough to lead to atraumatic fractures and thus markedly diminish life quality and expectancy. The estimated prevalence for liver-related osteoporosis is between 20-420/100000 of the general population, and fractures between 60-880/100000. It should be kept in mind that up to 40% of patients with chronic liver disease may experience a fracture. The pathogenic mediators include fibronectin, insulin like growth factor-I, and various cytokines, but decreased vitamin D and/or treatment with corticosteroids contribute to worsening bone health. Despite the advances in bone biology that have shed some light on the pathogenesis of this bone loss, treatment options remain nonspecific and tightly linked to treatments of other forms of osteoporosis. Thus, treatment should include calcium and vitamin D supplementation in all patients with chronic liver disease. Therapy with bisphosphonates should be considered, especially in patients receiving corticosteroids. This review focuses on the prevalence of this entity as well as the evidence available with regard to the pathogenesis of bone loss in liver disease, the diagnostic steps required in all patients, and the therapeutic options available. Copyright © 2014 Baishideng Publishing Group Inc. All rights reserved.",Calcium;Fibronectin;Fracture;Insulin like growth factor-I;Liver disease;Osteoporosis;Pathogenesis;Prevalence;Therapy;Vitamin D;antiviral therapy;autoimmune liver disease;bone density;bone matrix;bone mineralization;bone remodeling;calcium absorption;cholestasis;chronic liver disease;corticosteroid therapy;disease association;fragility fracture;graft recipient;hemochromatosis;hepatitis;hepatitis B;hepatitis C;human;iron overload;liver cirrhosis;liver disease/dt [Drug Therapy];liver graft;liver transplantation;nonalcoholic fatty liver;nonhuman;ossification;osteoblast;osteoclast;osteocyte;osteolysis;phosphate metabolism;review;risk assessment;virus hepatitis;vitamin D metabolism;vitamin supplementation;Wilson disease;bilirubin;bisphosphonic acid derivative;corticosteroid/dt [Drug Therapy];interleukin 6;osteoclast differentiation factor;osteoprotegerin;penicillamine;phosphate;sex hormone;somatomedin;somatomedin C;ursodeoxycholic acid,"Nakchbandi, I. A.",2014,28 Jul,http://dx.doi.org/10.3748/wjg.v20.i28.9427,0,0,
1375,Low-copper diet as a preventive strategy for Alzheimer's disease,"Copper is an essential element, and either a copper deficiency or excess can be life threatening. Recent studies have indicated that alteration of copper metabolism is one of the pathogenetic mechanisms of Alzheimer's disease (AD). In light of these findings, many researchers have proposed preventive strategies to reduce AD risk. Because the general population comes in contact with copper mainly through dietary intake, that is, food 75% and drinking water 25%, a low-copper diet can reduce the risk of AD in individuals with an altered copper metabolism. We suggest that a diet-gene interplay is at the basis of the ""copper phenotype"" of sporadic AD. Herein, we describe the pathways regulating copper homeostasis, the adverse sequelae related to its derangements, the pathogenic mechanism of the AD copper phenotype, indications for a low-copper diet, and future perspectives to improve this preventive strategy. © 2014 Elsevier Inc.",Alzheimer's disease;Copper;Diet;Diet-gene interaction;Drinking water;Food;Genetics;Metabolism;Prevention;Susceptibility;Alzheimer disease/pc [Prevention];atherosclerosis;atp7a gene;ATP7B gene;brain level;carcinogenesis;clinical feature;copper deficiency;copper metabolism;diet supplementation;disease association;disease model;experimental animal;food intake;gastrointestinal absorption;gene;homeostasis;human;intracellular transport;liver cell;low copper diet;Menkes syndrome/et [Etiology];neuropathology;nonhuman;pathophysiology;priority journal;review;risk factor;spinal cord disease;urinary excretion;Wilson disease/et [Etiology];metallothionein/ec [Endogenous Compound];zinc,"Squitti, R.;Siotto, M.;Polimanti, R.",2014,September,http://dx.doi.org/10.1016/j.neurobiolaging.2014.02.031,0,0,
1376,Anionic linear globular dendrimer-G2-ciprofloxacin nano-conjugate: Novel agent against wilson disease cell model,"Inherited defect of the gene ATP7B causes malexcretion of copper in the bile and leads to several complications that need treatment to deplete it from organs. Current therapy of Wilson disease, D-penicillamine has very serious side effects and drug with optimum therapeutic effects and minimum side effects is of importance. In the present study ciprofloxacin was conjugated with an anionic globular dendrimer to lower the intracellular copper concentration. The results showed its efficacy and safety to certain levels. Based on the results, ciprofloxacin-anionic linear globular dendrimer conjugate can be a useful option to reduce intracellular copper concentration and an investigational therapeutic agent in Wilson disease. © 2014 Bentham Science Publishers.",Copper;Dendrimer-ciprofloxacin nano-particle;Fluoroquinolone;Metal ions;Wilson disease;article;cell level;concentration (parameters);drug conjugation;drug cytotoxicity;drug efficacy;drug safety;drug structure;human;human cell;ic 50;priority journal;Wilson disease/dt [Drug Therapy];anion;ciprofloxacin/an [Drug Analysis];ciprofloxacin/cm [Drug Comparison];ciprofloxacin/dt [Drug Therapy];copper/ec [Endogenous Compound];dendrimer/an [Drug Analysis];dendrimer/dt [Drug Therapy];penicillamine/cm [Drug Comparison],"Karimi, N.;Aghasadeghi, M. R.;Yaghmaei, P.;Moghaddam, H. F.;Nassiri-Koopaei, N.;Moloudian, H.;Najafi, S.;Shandiz, S. A.;Ardestani, M. S.",2014,August,,0,0,
1377,Wing-beating tremor,,abduction;adult;article;brain damage;case report;chronic liver disease/di [Diagnosis];computer assisted tomography;daily life activity;disease duration;dysarthria;echography;flapping tremor/co [Complication];flapping tremor/dt [Drug Therapy];general pathological parameters;human;kayser fleischer ring;male;mesencephalon;muscle hypertonia;neurologic examination;priority journal;protein blood level;thalamus;Wilson disease/di [Diagnosis];wing beating tremor/co [Complication];wing beating tremor/dt [Drug Therapy];young adult;ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Mahajan, R.;Zachariah, U.",2014,,http://dx.doi.org/10.1056/NEJMicm1312190,0,0,
1378,A blue-grey discolored man,,Addison disease;aged;argyria;arm disease;case report;chrysiasis;drug induced disease;drug withdrawal;face disorder;finger nail;hemochromatosis;human;human tissue;laboratory test;laser;male;nail color defect;note;priority journal;skin abrasion;skin biopsy;skin discoloration/si [Side Effect];skin pigmentation;very elderly;Wilson disease;adsorgan/ae [Adverse Drug Reaction];dermatological agent;hydroquinone;penicillamine;sodium thiosulfate;unclassified drug,"Serrano, P. F. C.;Ales-Fernandez, M.;Rios-Martin, J. J.;Camacho-Martinez, F. M.",2014,February,http://dx.doi.org/10.1016/j.jaad.2013.08.044,0,0,
1379,Abnormal copper metabolism in Niemann-Pick disease type C mimicking Wilson's disease,"Background: Niemann-Pick disease type C is a rare lysosomal storage disease in infants, adolescents and adults. Aim: We investigated a family with two siblings who have adult-onset Niemann-Pick disease type C presenting with abnormal copper metabolism mimicking Wilson's disease. Methods: Case 1 was a 26-years-old Japanese man without consanguinity, and was referred to the hospital outpatient clinic for recent gait disturbance and intellectual deterioration developing since the age of 20 years. He was tentatively diagnosed as a heterozygous carrier of Wilson's disease, because his brother (case 2) had been diagnosed with Wilson's disease. He presented with dementia, dysphagia, dystonia, ataxia and downward gaze palsy. Laboratory study showed mild liver dysfunction and moderate splenomegaly. Magnetic resonance images showed a thin corpus callosum and narrowed deep white matter. Case 2 35 years-of-age, and had developed psychiatric and motor symptoms since 20 years-of-age. He had been treated for Wilson's disease for 11 years due to a copper deposit in his liver and abnormal copper metabolism. Symptoms had exacerbated gradually despite chelation therapy and tube feeding with gastrostomy for a year. Molecular diagnostics for Niemann-Pick disease type C were carried out. Results: Filipin staining in cultured skin fibroblasts of case 1 was partially positive, and gene analysis showed that both siblings had compound heterozygosity for p.G992R in exon 20 and IVS6-3 C>G of NPC1. Administration of miglustat for 3 months partially ameliorated their intellectual and motor dysfunction. Conclusion: The differential diagnosis between Niemann-Pick disease type C and Wilson's disease is important for specific treatment. Copyright © 2014 Japanese Society of Neurology and Wiley Publishing Asia Pty Ltd.",Copper metabolism;Metabolic disorders;Molecular genetics;Niemann-Pick disease type C;Wilson's disease;adult;airway obstruction;article;ataxia;case report;ceruloplasmin blood level;controlled study;contusion;copper blood level;dementia;differential diagnosis;dysarthria;dysphagia;dystonia;eye fixation;gait;gaze paralysis;gene mutation;heterozygosity;human;human cell;human tissue;liver biopsy;liver dysfunction;male;motor dysfunction/dt [Drug Therapy];Niemann Pick disease/di [Diagnosis];nuclear magnetic resonance imaging;polymerase chain reaction;priority journal;reverse transcription polymerase chain reaction;skin fibroblast;splenomegaly;Wilson disease/dt [Drug Therapy];filipin;miglustat/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Sakiyama, Y.;Narita, A.;Osawa, S.;Nanba, E.;Ohno, K.;Otsuka, M.",2014,01 Nov,http://dx.doi.org/10.1111/ncn3.122,0,0,
1380,Identification and characterization of a novel splice-site mutation in the Wilson disease gene,"This study aimed to identify aberrant transcripts of the new splice-site mutation c.3244-2ANC in the Wilson disease (WD) gene (ATPase, Cu++transporting, beta polypeptide, ATP7B) and discuss its genotype and clinical phenotype. DNA and RNA were extracted from peripheral blood lymphocytes, amplified by polymerase chain reaction (PCR) and nested reverse transcription PCR (RT-nested PCR) to characterize the aberrant transcripts. RT-nested PCR product sequencing comparison showed that c.3244-2ANC splice-site mutation caused aberrant transcripts and formatted a newsplice acceptor. Patient carrying the splice-sitemutation c.3244-2ANC presented early onset age, severe clinical manifestations, and poor prognosis. WD patients with the splice-site mutation show severe clinical manifestations, indicating that aberrant transcripts have important implications for WD phenotype. Copyright © 2014 Elsevier B.V.",Aberrant transcripts;atp7b;Gene mutation;Genotype;Phenotype;Splice-site;Wilson disease;abdominal radiography;adolescent;adult;article;case report;chemical analysis;controlled study;copper blood level;denaturing high performance liquid chromatography;disease severity;DNA extraction;echography;female;follow up;gene identification;genetic transcription;heterozygote;human;hypertransaminasemia;laboratory test;limb tremor;liver cirrhosis;liver protection;missense mutation;muscle tone;nuclear magnetic resonance imaging;nucleotide sequence;onset age;peripheral lymphocyte;point mutation;polymerase chain reaction;portal hypertension;prognosis;protein blood level;reverse transcription polymerase chain reaction;RNA extraction;speech sound disorder;young adult;aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];DNA/ec [Endogenous Compound];gluconate zinc/cb [Drug Combination];penicillamine/cb [Drug Combination];RNA/ec [Endogenous Compound],"Diao, S. P.;Hong, M. F.;Huang, Y. Q.;Wei, Z. S.;Su, Q. X.;Peng, Z. X.;Yu, Q. Y.;Liu, A. Q.;Chen, J.;Hu, L.",2014,15 Oct,http://dx.doi.org/10.1016/j.jns.2014.07.031,0,0,
1381,Delayed appearance of wing-beating tremor after liver transplantation in a patient with Wilson disease,"Orthotopic liver transplantation (OLT) is the sole etiological treatment for Wilson disease (WD), but several neurological complications after OLT have been reported. We report a WD patient who developed a unilateral wing-beating tremor 6 years after OLT. New neurological symptoms develop immediately after OLT in most cases. In our patient, the onset of extrapyramidal symptoms was at a prolonged interval after OLT. To our knowledge this is the first patient with delayed extrapyramidal symptoms after OLT in WD where the pathophysiology of these late extrapyramidal symptoms is still unknown. © 2014 Published by Elsevier Ltd.",Delayed;Orthotopic liver transplantation;Tremor;Wilson disease;adult;anamnesis;article;case report;ceruloplasmin blood level;contrast enhancement;copper metabolism;disease classification;extrapyramidal symptom/co [Complication];eye disease/di [Diagnosis];facial nerve paralysis;female;hemifacial spasm;human;human tissue;immunosuppressive treatment;kayser fleischer ring/di [Diagnosis];liver biopsy;liver transplantation;lymphocytic infiltration/di [Diagnosis];middle aged;nuclear magnetic resonance imaging;ophthalmology;parotid gland cancer/su [Surgery];positron emission tomography;postoperative complication/co [Complication];priority journal;staining;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];wing beating tremor/co [Complication];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cyclosporin;penicillamine,"Kim, J. S.;Kim, S. Y.;Choi, J. Y.;Kim, H. T.;Oh, Y. S.",2014,August,http://dx.doi.org/10.1016/j.jocn.2013.10.036,0,0,
1382,A boy with sapphire thumbnails: Lunulae ceruleae,,article;case report;child;follow up;human;lunulae ceruleae;male;medical history;nail color defect;school child;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Kamate, M.;Prashanth, G. P.;Gandhi, S.",2014,July,http://dx.doi.org/10.1007/s12098-014-1341-7,0,0,
1383,Small fiber dysfunction in patients with Wilson's disease,"Objective: Patients with Wilson's disease (WD) may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodoparesponsive parkinsonism. Method: We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT). Results: Two men and 2 women (33+/-3.5 years) with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1). Discussion: A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy).",Autonomic nervous system diseases;Small fiber neuropathy;Wilson's disease;adult;article;ataxic gait;basal ganglion;bradykinesia;burn;case report;consciousness disorder;controlled study;diagnostic test;disease course;drug withdrawal;dystonia;electromyography;female;human;human tissue;hyperreflexia;leg pain;male;nerve conduction;neurologic disease;neurologic examination;nuclear magnetic resonance imaging;paresthesia;parkinsonism/dt [Drug Therapy];psychosis;skin biopsy;skin wrinkling test;small fiber dysfunction;tremor;urine incontinence;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];biperiden/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];levodopa/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pramipexole/dt [Drug Therapy];vitamin B complex/dt [Drug Therapy],"Gondim, F. A. A.;Araujo, D. F.;Oliveira, I. S.;do Vale, O. C.",2014,August,http://dx.doi.org/10.1590/0004-282X20140090,0,0,
1384,The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma,"Bcl-2 and other anti-apoptotic proteins are associated with defective caspase-dependent apoptotic pathways, resulting in chemoresistance. We have previously shown that ATN-224, a copper chelator drug, induces cell death in murine thymic lymphoma cells transfected with Bcl-2. In the current study, we tested whether ATN-224 was effective in diffuse large B cell lymphoma (DLBCL) cells, which have increased anti-apoptotic proteins through translocation or amplification. We found that nanomolar concentrations of ATN-224 induced cell death in DLBCL cells independent of Bcl-2, Bcl-xL or Mcl-1 status. ATN-224 treatment resulted in mitochondrial dysfunction, release of apoptosis-inducing factor (AIF) and induction of caspase-independent cell death. In addition, ATN-224 degraded Mcl-1 and enhanced the effect of the BH3 mimetic ABT-263. These findings indicate that ATN-224 has potential as a therapeutic for the treatment of DLBCL. Induction of caspase-independent cell death in apoptosis-resistant DLBCL would provide a therapeutic alternative for the treatment of refractory disease. We thank Amanda Bahe for technical assistance and Dr Anthony Letai (Dana-Farber Cancer Institute) for the SUDHL-8 and SUDHL-4R2 cells. This study was supported by the National Cancer Institute Grants CA09213 (K.L.), CA71768 (M.M.B.), CA130805 (K.L., M.M.B., M.E.T.) and CA023074 (M.E.T.). A.P.M. was supported by U01 CA151461-02, P50 HL 107186-01 and H Foundation Funds. A.P.M. is a consultant to Wilson Therapeutics AB who is developing ATN-224 for Wilson disease and has a small amount of equity in the company. All other authors declare no conflict of interest.",Bcl-2;Bcl-xL;Cytochrome c oxidase;Lymphoma;Mcl-1;Mitochondria;apoptosis;article;B-Cell lymphoma cell line;controlled study;cytokine release;disorders of mitochondrial functions;drug efficacy;drug potentiation;gene amplification;gene translocation;large cell lymphoma;priority journal;protein degradation;apoptosis inducing factor/ec [Endogenous Compound];caspase/ec [Endogenous Compound];caspase 3/ec [Endogenous Compound];choline tetrathiomolybdate/cb [Drug Combination];choline tetrathiomolybdate/it [Drug Interaction];choline tetrathiomolybdate/to [Drug Toxicity];choline tetrathiomolybdate/pd [Pharmacology];navitoclax/cb [Drug Combination];navitoclax/it [Drug Interaction];navitoclax/pd [Pharmacology];protein bcl 2/ec [Endogenous Compound];protein bcl xl/ec [Endogenous Compound];protein mcl 1/ec [Endogenous Compound],"Lee, K.;Hart, M. R.;Briehl, M. M.;Mazar, A. P.;Tome, M. E.",2014,July,http://dx.doi.org/10.3892/ijo.2014.2396,0,0,
1385,"Wilson disease: Clinical manifestations, diagnosis, and treatment",,acute liver failure;aminotransferase blood level;anarthria;ascites;behavior change;blood clotting disorder;ceruloplasmin blood level;clinical feature;coordination disorder;copper blood level;depression;drug efficacy;drug tolerability;dysarthria;dysautonomia;dysphagia;dysphonia;dystonia;esophagus varices;exhibitionism;gait disorder;hepatic encephalopathy;hepatomegaly;human;hyperbilirubinemia;hypersalivation;hypoalbuminemia;hypouricemia;impulsiveness;jaundice;liver biopsy;mood change;nuclear magnetic resonance imaging;parkinsonism;patient monitoring;personality disorder;priority journal;prognosis;psychosis;review;serology;slit lamp;splenomegaly;stomach varices;thrombocytopenia;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Schilsky, M. L.",2014,,http://dx.doi.org/10.1002/cld.349,0,0,
1386,Resolution of MRI findings of copper deficiency myeloneuropathy in a patient with Wilson's disease,,copper deficiency myeloneuropathy;copper metabolism;disease course;drug withdrawal;human;neurologic disease;neuromonitoring;note;nuclear magnetic resonance imaging;treatment outcome;Wilson disease;zinc,"da Silva Jr, F. P.;Machado, A. A. C.;Lucato, L. T.;Barbosa, E. R.",2014,March,http://dx.doi.org/10.1590/0004-282X20130226,0,0,
1387,Psychosis in an adolescent with Wilson's disease: A case report and review of the literature,"Neuropsychiatric manifestations are common in Wilson's disease and mainly include extrapyramidal and cerebellar symptoms. Presentations with psychotic symptoms have been described less frequently. In this report we present the case of a young boy with Wilson's disease who developed psychotic symptoms. A 12-year-old boy was diagnosed with Wilson's disease on the basis of the physical examination findings and low ceruloplasmin levels (8.1 mg/dl). After 2 weeks of being diagnosed with Wilson's disease, he developed an acute onset illness, characterized by delusion of persecution, fearfulness, hypervigilence and decreased sleep. These symptoms were not associated with any confusion, clouding of consciousness, hallucinations and affective symptoms. There was no past or family history of psychosis. One week after the onset of the symptoms he was prescribed tab penicillamine, initially 250 mg/day, which was increased to 500 mg/day after 3 days. After increase in the dose of penicillamine, his psychiatric symptoms worsened and led to hospitalization. A diagnosis of organic delusional disorder (F06.2) due to Wilson's disease was considered. Tab risperidone 1 mg/day was started, and the dose of penicillamine was reduced with which symptoms resolved. Whenever a young adolescent develops psychosis, especially of delusional type, the possibility of Wilson's disease must be considered.",adolescent;Psychosis;Wilson's disease;abdominal distension;abdominal pain;ascites;case report;ceruloplasmin blood level;child;confusion;consciousness disorder;copper blood level;decreased appetite;delusional disorder/co [Complication];delusional disorder/dt [Drug Therapy];drug dose increase;drug dose reduction;emotional disorder;fear;hallucination;hospitalization;human;irritability;liver disease;male;mood disorder;persecutory delusion;physical examination;portal hypertension;restlessness;review;sleep disorder;slit lamp;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];risperidone/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Grover, S.;Sarkar, S.;Jhanda, S.;Chawla, Y.",2014,01 Oct,http://dx.doi.org/10.4103/0019-5545.146530,0,0,
1388,Successful treatment of fulminant Wilson's disease without liver transplantation,"Fulminant Wilson's disease (WD) is life-threatening. The revised WD prognostic index (RWPI) has been used to predict the severity of the disease, with a score >=11 indicating fatal outcome without liver transplantation (LTx). We here report the case of a 10-year-old female patient with fulminant WD (RWPI, 16) who recovered fully after plasma exchange and continuous hemodiafiltration, followed by treatment with copper chelate agents. To the best of our knowledge, there have been five fulminant WD patients with RWPI >= 11 including the present patient, in whom LTx was not done. Based on the therapeutic modalities in these five cases, non-surgical treatment (blood purification and copper chelate agents) may be able to avoid LTx in fulminant WD even with very high RWPI, although preparation for LTx is necessary. © 2014 Japan Pediatric Society.",continuous hemodiafiltration;fulminant Wilson's disease;liver transplantation;plasma exchange;revised Wilson's disease prognostic index;article;case report;child;copper blood level;epistaxis;fatigue;female;fulminant Wilson disease/di [Diagnosis];fulminant Wilson disease/dt [Drug Therapy];fulminant Wilson disease/th [Therapy];headache;hepatic encephalopathy;human;human tissue;jaundice;liver biopsy;plasmapheresis;priority journal;school child;slit lamp;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];fresh frozen plasma;trientine/dt [Drug Therapy];unclassified drug;zinc acetate hydrate/dt [Drug Therapy],"Motobayashi, M.;Fukuyama, T.;Nakayama, Y.;Sano, K.;Noda, S.;Hidaka, Y.;Amano, Y.;Ikeda, S. I.;Koike, K.;Inaba, Y.",2014,June,http://dx.doi.org/10.1111/ped.12291,0,0,
1389,An early sign of wilson's disease: Dysarthria,,Copper;Dysarthria;abnormal behavior;case report;child;copper urine level;dysphagia;dystonia;human;letter;male;mastication;school child;slurred speech;urine level;voice disorder;Wilson disease;ceruloplasmin;penicillamine;trientine;unclassified drug;zincolac,"Lihite, R. J.;Choudhury, U.;Surender, G.;Pal, B.;Lahkar, M.",2014,,http://dx.doi.org/10.7860/JCDR/2014/7320.4196,0,0,
1390,Evidence for synergistic effects of PRNP and ATP7B mutations in severe neuropsychiatric deterioration,"Background: Wilson's disease (WD), a rare cause of neuropsychiatric deterioration, is associated with mutations in the ATP7B gene. Prion diseases are also rare causes of neuropsychiatric deterioration that can occur sporadically without an identifiable cause, or can be attributed to mutations in the PRNP gene. Case presentation: Here we describe a biological ""experiment of nature"" in which a patient presented with severe neuropsychiatric decline and strong biochemical evidence of WD. Genetic analysis revealed that he was a compound heterozygote for two ATP7B sequence variants (c.2165dupT, p.Arg723Glufs*32; and c.4039G > A, p.Gly1347Ser), the first having been reported once previously, and the second being novel. In addition, the patient was heterozygous for a PRNP variant, c.160G > A, p.Gly54Ser, that has been reported in a neuropsychiatric patient only once previously in association with a similarly severe clinical course of neuropsychiatric disease and early age of onset, but no accompanying information on ATP7B genotype. Of particular interest was the observation that the patient's older sister, who carried the same ATP7B genotype and laboratory evidence for biochemical WD but was clinically asymptomatic, lacked the PRNP variant allele. Conclusions: We propose that synergism may occur between at least some allelic variants of ATP7B and PRNP, possibly exerted through effects on cellular copper metabolism. Copyright © forbes et al.",atp7b;Copper;Movement disorder;Prion disease;Prion protein;prnp;PrP;Synergistic mutations;Wilson's disease;adult;aggression;allele;amino acid substitution;anxiety disorder/dt [Drug Therapy];article;ataxia;ATP7B gene;bipolar disorder/dt [Drug Therapy];brain atrophy;case report;ceruloplasmin blood level;chelation therapy;cognitive defect;computer assisted tomography;copper blood level;copper metabolism;depression/dt [Drug Therapy];disease course;disease severity;DNA sequence;drug substitution;drug withdrawal;dysarthria;dystonia;gene;gene mutation;genetic analysis;genetic association;genotype;heterozygote;human;hyperreflexia;laboratory test;male;mental deterioration;mental instability;muscle rigidity;mutational analysis;neurologic examination;nuclear magnetic resonance imaging;onset age;prion disease/di [Diagnosis];prion disease/et [Etiology];PRNP gene;psychosexual disorder;restlessness;single nucleotide polymorphism;social disability;unspecified side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];antidepressant agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];lithium;mood stabilizer/dt [Drug Therapy];neuroleptic agent/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];propranolol;quetiapine;trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc/cm [Drug Comparison];zinc/dt [Drug Therapy];zopiclone,"Forbes, N.;Goodwin, S.;Woodward, K.;Morgan, D. G.;Brady, L.;Coulthart, M. B.;Tarnopolsky, M. A.",2014,February 20,http://dx.doi.org/10.1186/1471-2350-15-22,0,0,
1391,Reply: Bilateral pallidal stimulation for wilson's disease,,adult;case report;copper metabolism;dystonia;feeding;human;letter;limited mobility;male;pain;palliative therapy;Parkinson disease/dt [Drug Therapy];priority journal;Wilson disease;trientine/dt [Drug Therapy];zinc ion/dt [Drug Therapy];zinc ion/po [Oral Drug Administration],"Sidiropoulos, C.",2014,July,http://dx.doi.org/10.1002/mds.25901,0,0,
1392,Importance of adequate decoppering in wilson's disease,,brain depth stimulation;caregiver burden;chelation;copper chelation;copper metabolism;gastrostomy;generalized dystonia/th [Therapy];human;letter;limited mobility;medication compliance;pain;palliative therapy;patient compliance;priority journal;therapy effect;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];copper/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Annu, A.;Mohit, B.",2014,July,http://dx.doi.org/10.1002/mds.25900,0,0,
1393,A modified heterotopic auxiliary living donor liver transplantation: Report of a case,"Liver transplantation is regarded as an effective treatment for Wilson's disease (WD), and recently has been shown to improve not only hepatic but also neurologic manifestations. Conventional auxiliary liver transplantation for WD is orthotopic liver transplantation and heterotopic liver transplantation. But the conventional procedure could not avoid the problem of space, functional competition, hemodynamic variation. Here we report a case of heterotopic auxiliary living-donor liver transplantation (HALDLT) to treat WD. We modified the operation to have a splenectomy, implant graft into the splenic fossa. The patient recovered well after the transplantation and has been symptom-free during a 5-year follow-up. This modified operation is more safe and simple. HALDLT might be an effective treatment for WD patients with splenomegaly.",Heterotopic liver transplantation;Left hepatectomy;Splenectomy;Splenic fossa;Wilson's disease;abdominal radiography;article;ascites/di [Diagnosis];bilirubin blood level;case report;ceruloplasmin blood level;child;clinical effectiveness;clinical feature;computer assisted tomography;copper blood level;copper metabolism;Doppler echography;drug dose reduction;drug withdrawal;end to end anastomosis;female;follow up;heterotopic auxiliary living donor liver transplantation;histopathology;human;human tissue;immunosuppressive treatment;leukopenia/di [Diagnosis];liver cirrhosis;liver function;liver graft;liver resection;liver transplantation;postoperative period;prothrombin time;school child;splenomegaly/di [Diagnosis];surgical approach;suture;symptomatology;thrombocytopenia/di [Diagnosis];treatment response;Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];methylprednisolone/do [Drug Dose];penicillamine;phytate;prednisone;tacrolimus;technetium 99m;zinc sulfate,"Dou, K.;Wang, D.;Tao, K.;Yue, S.;Ti, Z.;Song, Z.;Li, L.;He, Y.;Hou, X.",2014,May-June,,0,0,
1394,Chelating polymeric beads as potential therapeutics for Wilson's disease,"Wilson's disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson's disease. © 2014 Elsevier B.V. All rights reserved.","Chelators;Copper chelation;Polymer beads;Wilson's disease;animal experiment;animal model;animal tissue;article;brain level;carcass;chelation;computer assisted emission tomography;controlled study;drug elimination;drug half life;female;gastrointestinal absorption;gastrointestinal tract;heart;isotope labeling;kidney;liver level;lung;nonhuman;polymerization;priority journal;radiation absorption;radioactivity;rat;spleen;Wilson disease;8 quinolinol/dv [Drug Development];8 quinolinol/po [Oral Drug Administration];8 quinolinol/pr [Pharmaceutics];8 quinolinol/pk [Pharmacokinetics];chelating agent/dv [Drug Development];chelating agent/po [Oral Drug Administration];chelating agent/pr [Pharmaceutics];chelating agent/pk [Pharmacokinetics];copper;copper 64;cupric ion;iodine 125;n,n di(2 pyridylmethyl)amine/dv [Drug Development];n,n di(2 pyridylmethyl)amine/po [Oral Drug Administration];n,n di(2 pyridylmethyl)amine/pr [Pharmaceutics];n,n di(2 pyridylmethyl)amine/pk [Pharmacokinetics];poly(glycidyl methacrylate co ethylene dimethacrylate)/dv [Drug Development];poly(glycidyl methacrylate co ethylene dimethacrylate)/po [Oral Drug Administration];poly(glycidyl methacrylate co ethylene dimethacrylate)/pr [Pharmaceutics];poly(glycidyl methacrylate co ethylene dimethacrylate)/pk [Pharmacokinetics];polymer/dv [Drug Development];polymer/po [Oral Drug Administration];polymer/pr [Pharmaceutics];polymer/pk [Pharmacokinetics];trientine/dv [Drug Development];trientine/po [Oral Drug Administration];trientine/pr [Pharmaceutics];trientine/pk [Pharmacokinetics];unclassified drug","Mattova, J.;Pouckova, P.;Kucka, J.;Skodova, M.;Vetrik, M.;Stepanek, P.;Urbanek, P.;Petrik, M.;Novy, Z.;Hruby, M.",2014,01 Oct,http://dx.doi.org/10.1016/j.ejps.2014.05.002,0,0,
1395,D-penicillamine-induced membranous nephropathy,,adult;anemia;basement membrane;case report;drug withdrawal;female;female infertility;follow up;foot edema;human;human tissue;jaundice;kidney biopsy;letter;membranous glomerulonephritis/di [Diagnosis];membranous glomerulonephritis/si [Side Effect];prevalence;proteinuria;Wilson disease/dt [Drug Therapy];young adult;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];vitamin;zinc,"Kumar, R. P. S.;Prasad, N. S.;Tirumavalavan, S.;Fernando, M. E.",2014,May-June,http://dx.doi.org/10.4103/0971-4065.132024,0,0,
1396,Wilson's disease - A rare cause of renal tubular acidosis with metabolic bone disease,"We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson's disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease.",Metabolic bone disease;renal tubular acidosis;Wilson's disease;adolescent;article;case report;dual energy X ray absorptiometry;echography;electromyography;follow up;gastrointestinal endoscopy;human;kidney tubule acidosis/di [Diagnosis];limb weakness;male;nerve conduction;nuclear magnetic resonance imaging;osteoporosis/di [Diagnosis];slit lamp;urinalysis;Wilson disease/di [Diagnosis];bicarbonate/po [Oral Drug Administration];zinc/po [Oral Drug Administration],"Subrahmanyam, D. K. S.;Vadivelan, M.;Giridharan, S.;Balamurugan, N.",2014,May-June,http://dx.doi.org/10.4103/0971-4065.132017,0,0,
1397,Major depression caused by Wilson's disease,,adult;anxiety;case report;computer assisted tomography;copper blood level;depression/dt [Drug Therapy];drug dose titration;follow up;human;hypersalivation;letter;male;mood disorder;muscle rigidity;neurologic examination;nuclear magnetic resonance imaging;psychosis;tremor;Wilson disease;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];escitalopram;mirtazapine/dt [Drug Therapy];paliperidone;penicillamine,"Araujo-de-Freitas, L.;Rocha, M.;Gondim, V.;Quarantini, L.;Miranda-Scippa, A.",2014,Apr./June,http://dx.doi.org/10.1590/1516-4446-2013-1188,0,0,
1398,Liver transplantation in neurological Wilson's disease: Is there indication? a case report,"Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In this disease, inadequate hepatic excretion leads to copper accumulation in the liver, brain, kidney, and cornea. Severe neurological symptoms can develop in patients with WD, often in the absence of relevant liver damage: it is unclear whether liver transplantation (LT) could reverse neurological symptoms, and at present LT is not recommended in this setting. We report a case of regression of neurological symptoms in a patient affected by WD with prevalent neurological involvement. A 19-year-old man with disabling neuropsychiatric symptoms from WD that included frontal ataxia, akinesia, dystonia, tremors, and behavioral disorders in the presence of preserved liver function (Model for End-Stage Liver Disease score = 7; Child-Turcotte-Pugh score = A5) underwent LT in November 2009. At the time of LT, encephalic magnetic resonance imaging (MRI) indicated diffuse neurodegenerative alterations involving subtentorial and supratentorial structures; bilateral Kayser-Fleischer ring was present. Four years after LT, laboratory tests show normalized copper metabolism and excellent liver function test results. Encephalic MRI shows a substantial improvement of already-known signal alterations at nuclei thalamus and putamen, mesencephalon, and pons. Kayser-Fleischer ring disappeared from the right eye, but a little remnant is still visible in the left eye. At neurological examination, all of the previous symptoms and signs are no longer present and behavioral disorders are no longer present; psychosocial functions are completely restored. The present case provides some evidence that LT may be a valid therapeutic option for WD patients with marked neurological impairment, particularly in those no longer responsive to chelation therapy. Copyright © 2014 Elsevier Inc. All rights reserved.",adult;aggressiveness;akinesia;anxiety;article;ataxia;basal ganglion;behavior disorder;case report;cerebellum atrophy;Child Turcotte Pugh score;copper metabolism;degenerative disease;disease severity;drug substitution;drug withdrawal;dysarthria;dyslexia;dystonia;emotional disorder;extrapyramidal syndrome;focal dystonia;follow up;human;immunosuppressive treatment;laboratory test;liver function;liver function test;liver transplantation;male;mesencephalon;Model For End Stage Liver Disease Score;mood disorder;neuroimaging;neurologic disease;neurologic examination;nuclear magnetic resonance imaging;pons;postoperative period;psychologic assessment;putamen;remission;restlessness;scoring system;slit lamp;social psychology;thalamus;treatment indication;tremor;walking difficulty;Wilson disease/dt [Drug Therapy];young adult;cyclosporin;everolimus/cb [Drug Combination];mycophenolic acid/cb [Drug Combination];penicillamine/dt [Drug Therapy];tacrolimus;zinc/dt [Drug Therapy],"Mocchegiani, F.;Gemini, S.;Vincenzi, P.;Montalti, R.;Vecchi, A.;Nicolini, D.;Federici, A.;Coletta, M.;Pansini, M.;Lanari, J.;Svegliati Baroni, G.;Risaliti, A.;Vivarelli, M.",2014,01 Sep,http://dx.doi.org/10.1016/j.transproceed.2014.07.059,0,0,
1399,Wilson's disease presenting as rapid eye movement sleep behavior disorder: A possible window to early treatment,"Objective: To describe characteristics of REM sleep behavior disorder in Wilson's disease. Method: Questionnaire-based interviews (patients and relatives), neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results: Four Wilson's disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion: This first description of REM sleep behavior disorder in Wilson's disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson's disease and adds further evidence to the parallelism of Parkinson's disease and Wilson's disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in a-synucleinopathies. In Wilson's disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson's disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in ""pre-clinical"" Parkinson's disease. Copyright © 2014 Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.",Parasomnias;Parkinsonian syndromes;Rapid eye movement sleep behavior disorder;Tegmentum;Wilson's disease;adult;article;case report;daily life activity;echography;female;human;male;Mini Mental State Examination;neurologic examination;nuclear magnetic resonance imaging;parasomnia;parkinsonism;polysomnography;protein blood level;questionnaire;sleep quality;unpleasant dream;Wilson disease/dt [Drug Therapy];young adult;baclofen;biperiden;botulinum toxin;ceruloplasmin/ec [Endogenous Compound];copper;omeprazole;trazodone;trientine/dt [Drug Therapy];zolpidem,"Tribl, G. G.;Bor-Seng-Shu, E.;Trindade, M. C.;Lucato, L. T.;Teixeira, M. J.;Barbosa, E. R.",2014,01 Sep,http://dx.doi.org/10.1590/0004-282X20140118,0,0,
1400,Psychiatric signs and symptoms in treatable inborn errors of metabolism,"Possible underlying organic causes of psychiatric symptoms can be overlooked in the clinical setting. It is important to increase awareness amongst psychiatric and neurological professionals with regard to certain inborn errors of metabolism as, in some cases, disease-specific therapies are available that can, for instance, treat underlying metabolic causes. The following article describes the basic pathophysiology, clinical and neurological features, and available diagnostic procedures of six treatable metabolic diseases that are associated with neuropsychiatric symptoms: Wilson's disease, cerebrotendinous xanthomatosis, porphyrias, homocysteinemia, urea cycle disorders, and Niemann-Pick disease type C (NP-C). NP-C is taken as a particularly relevant example because, while it is traditionally considered to be a condition that presents with severe neurological and systemic manifestations in children, an increasing number of patients are being detected who have the adolescent- or adult-onset form, which is frequently associated with neuropsychiatric signs. A notable proportion of adult-onset cases have been reported where NP-C has mistakenly been diagnosed and treated as a psychiatric condition, usually based on patients' initial presentation with psychotic or schizophrenia-like symptoms. Underlying organic causes of psychiatric disorders such as psychosis should be considered among patients with atypical symptoms and/or resistance to standard therapy. Alongside improved frameworks for additional multidisciplinary diagnostic work in patients with suspected organic disease, the development of convenient and affordable biochemical screening and/or diagnostic methods has enabled new ways to narrow down differential diagnoses. © 2014 The Author(s).",Cognitive impairment;Diagnosis;Metachromatic leukodystrophy;Niemann-Pick disease type C;Organic psychosis;Psychosis;cerebrotendinous xanthomatosis;chelation therapy;clinical feature;congenital erythropoietic porphyria;diagnostic procedure;disease association;eye disease;gastrointestinal symptom;genetics;hemofiltration;hepatic porphyria;human;hyperhomocysteinemia;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/su [Surgery];liver disease;maintenance drug dose;mental disease;neurologic disease;neuropsychology;newborn screening;Niemann Pick disease;organic brain syndrome;pathogenesis;pathophysiology;porphyria;priority journal;review;urea cycle disorder;vitamin supplementation;Wilson disease;chenodeoxycholic acid;homocysteine/ec [Endogenous Compound];metallothionein;penicillamine;trientine,"Nia, S.",2014,September,http://dx.doi.org/10.1007/s00415-014-7396-6,0,0,
1401,Atypical neuroimaging in Wilson's disease,"Wilson's disease is a rare metabolic disease involving copper metabolism. Neuroimaging plays an important part in evaluation of patients with a neuropsychiatric presentation. We present a case of a 14-year-old girl with atypical confluent white matter disease and cystic degeneration on MRI, with a rapidly progressive course, who succumbed to complications despite treatment with trientine. Wilson's disease should be considered as a differential for leucoencephalopathy in young patients with progressive neurological disease for its early recognition and optimum outcome. Copyright 2014 BMJ Publishing Group. All rights reserved.",abnormal posture;adolescent;alanine aminotransferase blood level;albumin blood level;alkaline phosphatase blood level;article;aspartate aminotransferase blood level;attention disturbance;Babinski reflex;behavior disorder;bilirubin blood level;bradykinesia;brain cyst;case report;ceruloplasmin blood level;chronic liver disease/di [Diagnosis];cognitive defect;copper urine level;cornea disease;dystonia;female;human;hyperbilirubinemia;hypoalbuminemia;iron deficiency anemia;Kayser Fleisher ring;leukodystrophy;liver function test;muscle rigidity;neuroimaging;nuclear magnetic resonance imaging;priority journal;prothrombin time;psychomotor disorder;speech disorder;splenomegaly;thinking impairment;thrombocytopenia;urine level;walking difficulty;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];serum albumin/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Patell, R.;Dosi, R.;Joshi, H. K.;Storz, D.",2014,,http://dx.doi.org/10.1136/bcr-2013-200100,0,0,
1402,Coombs negative hemolytic anaemia in wilsons disease,"Wilson's disease is a rare inherited disorder of copper metabolism. Liver and brain are the main organs affected. Hemolytic anemia is a rare clinical manifestation of Wilson's Disease. We present a case of Wilson's Disease who presented with hemolytic anemia. © IDOSI Publications, 2014.",Hemolytic anemia;Wilson's disease;adult;article;blood transfusion;bone marrow biopsy;case report;Coombs negative hemolytic anemia/di [Diagnosis];Coombs negative hemolytic anemia/th [Therapy];dysarthria;ecchymosis;echography;female;hemolysis;hemolytic anemia/di [Diagnosis];hemolytic anemia/th [Therapy];hepatomegaly;human;normochromic normocytic anemia;pancytopenia;purpura;splenomegaly;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Halleys Kumar, E.;Radhakrishnan, A.",2014,,http://dx.doi.org/10.5829/idosi.wjms.2014.10.1.8284,0,0,
1403,Manifestation of wilson disease despite ongoing zinc-monotherapy and improvement after adding trientine: A case report,"Chelating agents and zinc are established treatments to prevent copper-induced intoxication in Wilson disease (WD). In this report, we present the case of a patient who developed a progressive impairment of liver function and mild neurological symptoms two years after initiation of a therapy with zinc. A combined treatment with a chelating agent (trientine) led to rapid and persistent recovery. The case underlines that treatment of WD needs continuous clinical and laboratory monitoring, as disease progression might also be observed after a transient period of therapeutic success. We also emphasize that a precise neurologic examination should be a mandatory part of the clinical follow up in WD patients. Copyright © 2014 Elsevier GmbH.",Trientine;Wilson disease;Zinc;adult;article;case report;chelation;clinical examination;clinical feature;copper metabolism;drug treatment failure;echography;elastography;family history;fatty liver/di [Diagnosis];follow up;hand tremor;Hashimoto disease;human;hypertransaminasemia;hypothyroidism;laboratory test;liver dysfunction/di [Diagnosis];liver injury/dt [Drug Therapy];male;monotherapy;outcome assessment;patient monitoring;priority journal;treatment refusal;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;albumin/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];cholinesterase/ec [Endogenous Compound];copper/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Hartmann, C. J.;Hefter, H.",2014,01 Dec,http://dx.doi.org/10.1016/j.baga.2014.06.002,0,0,
1404,Manic episode induced by discontinuance of D-penicillamine treatment in wilson's disease,"Wilson's disease (WD) is a rarely seen autosomal recessive inherited genetic disease of copper metabolism, which leads to various hepatic, orbital and neuropsychiatric disorders. Neuropsychiatric symptoms are due to degeneration that results from the acccumulation of copper in the neurons of the brain, especially in the basal ganglia. Clinicians should consider that toxicity of copper might trigger the episode in a patient with WD, who displays a manic episode. When persistent manic symptoms are encountered in WD, treatment of copper toxicity should be checked and necessary consultation should be performed. In this case report, a patient with WD who developed a manic episode as a result of stopping d-penicillamine treatment is presented, and improvement of clinical symptoms when d-penicillamine was added to the psychiatric treatment is emphasized. Copyright © 2014, Cukurova Univ Tip Fakultesi Psikiyatri Anabilim Dali. All rights reserved.",D-penicillamine;Manic episode;Wilson's disease;adult;aggressiveness;anger;article;bipolar mania/dt [Drug Therapy];case report;copper blood level;copper toxicity/dt [Drug Therapy];copper toxicity;female;follow up;human;insomnia;maintenance therapy;neurologic examination;remission;toxicity and intoxication/dt [Drug Therapy];treatment withdrawal;Wilson disease/dt [Drug Therapy];young adult;copper/ec [Endogenous Compound];olanzapine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];quetiapine/dt [Drug Therapy];risperidone/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Kenar, A. N. I.;Menteseoglu, H.",2014,,http://dx.doi.org/10.5455/bcp.20131021025658,0,0,
1405,"MR image mimicking the ""eye of the tiger"" sign in Wilson's disease",,adult;case report;dysarthria;dystonia;gait disorder;hand tremor;human;letter;male;nuclear magnetic resonance imaging;priority journal;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Litwin, T.;Karlinski, M.;Skowronska, M.;Dziezyc, K.;Golebiowski, M.;Czlonkowska, A.",2014,May,http://dx.doi.org/10.1007/s00415-014-7322-y,0,0,
1406,Copper Chelators: Chemical Properties and Bio-medical Applications,"Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons / year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu<sup>+</sup>/Cu<sup>2+</sup> a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined. Copyright © 2014 Bentham Science Publishers.",Bifunctional ligands;Copper chelators;Copper metabolism;Copper overload;Neurodegenerative diseases;Penicillamine;Tetrathiomolybdate;Trientine;Alzheimer disease/dt [Drug Therapy];chelation therapy;complex formation;crystal structure;food;homeostasis;human;nonhuman;physical chemistry;review;toxicity;Wilson disease/dt [Drug Therapy];ammonium tetrathiomolibdate/dt [Drug Therapy];chelating agent/dt [Drug Therapy];copper complex;cosmetic;drinking water;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug,"Tegoni, M.;Valensin, D.;Toso, L.;Remelli, M.",2014,,,0,0,
1407,Factors that predict mortality in children with Wilson disease associated acute liver failure and comparison of Wilson disease specific prognostic indices,"Background and Aims: Wilson disease (WD) associated acute liver failure (ALF) affects children more than adults. The predictors of mortality and outcome in patients without encephalopathy are not clear. We investigated the ability of prognostic factors and various models including model for end-stage liver disease (MELD) to predict mortality among children with WD and ALF. Methods: We analyzed the admission characteristics in 61 children <18 years with WD and ALF. Factors associated with mortality on univariate Cox regression analysis were analyzed by forward stepwise Cox hazards regression. The prognostic models such as Nazer's model, revised Kings College Model, and pediatric end-stage liver disease/model for end-stage liver disease (PELD/MELD) score were compared. Results: Of the 145 children <18 years with WD, 61 experienced ALF of whom 33 (54%) died, including 22/27 (81.5%) with encephalopathy and 11/34 (32.4%) without encephalopathy. The mean age of children with ALF was 9.7 years, 38(62.3%) were boys. Prognostic factors significant for mortality included encephalopathy, international normalized ratio, total proteins, total and direct bilirubin, alkaline phosphatase, serum creatinine, and white blood cell count. Forward stepwise Cox proportional hazards regression identified encephalopathy (hazard ratio 2.88; CI 1.1-7.4) and total bilirubin (hazard ratio 1.05; CI: 1.02-1.09) as predictors of outcome. The area under the receiver operating curve (AUC) of the Nazer index, revised King's College Criteria, and PELD/MELD were 0.74, 0.76, and 0.75, respectively. Conclusions: Mortality in children with WD and ALF is 54% including 81.5% with encephalopathy and 32.4% without encephalopathy. The prognostic models, MELD/PELD score, Nazer index and Kings College Criteria are comparable with a AUC between 0.74-0.76. Copyright © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.",Characteristics;Copper;Models;Survival;acute liver failure/di [Diagnosis];acute liver failure/dt [Drug Therapy];acute liver failure/ep [Epidemiology];adolescent;alkaline phosphatase blood level;antibiotic therapy;article;bilirubin blood level;child;controlled study;creatinine blood level;diagnostic test accuracy study;disease association;female;hazard ratio;hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/ep [Epidemiology];hospital admission;human;international normalized ratio;leukocyte count;liver biopsy;major clinical study;male;Model For End Stage Liver Disease Score;mortality;Nazer model;outcome assessment;pediatric end stage liver disease score;predictive value;priority journal;prognosis;proportional hazards model;protein blood level;receiver operating characteristic;revised Kings College model;risk factor;school child;scoring system;sensitivity and specificity;serum;step wise multiple regression;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];alkaline phosphatase/ec [Endogenous Compound];antibiotic agent/dt [Drug Therapy];antibiotic agent/iv [Intravenous Drug Administration];bilirubin/ec [Endogenous Compound];bilirubin glucuronide/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];fluconazole/dt [Drug Therapy];fluconazole/iv [Intravenous Drug Administration];glucose/dt [Drug Therapy];glucose/iv [Intravenous Drug Administration];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];protein/ec [Endogenous Compound];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration],"Devarbhavi, H.;Singh, R.;Adarsh, C. K.;Sheth, K.;Kiran, R.;Patil, M.",2014,01 Feb,http://dx.doi.org/10.1111/jgh.12356,0,0,
1408,Cytopenia and Bone Marrow Dysplasia in a Case of Wilson's Disease,"We describe a sixteen year old with Wilson's disease on copper chelation and subsequent high dose oral zinc who developed severe anemia and neutropenia. Bone marrow aspirate done to evaluate the cause of bicytopenia revealed trilineage dysplasia. Correlating the clinical context with bone marrow and biochemical parameters, copper deficiency was suspected and he was given a trial of therapy, following which the hematological parameters improved. This case highlights hypocupremia as a reversible cause of bone marrow dysplasia in patients with Wilson's disease on chelation, where serum copper levels are not useful in the diagnosis. We also believe that monitoring of the blood counts in patients on copper chelation may provide a clue to impending copper deficiency. Copyright © 2014, Indian Society of Haematology & Transfusion Medicine.",Bone marrow dysplasia;Cytopenia;Hypocupremia;Wilson's disease;adolescent;anemia/dt [Drug Therapy];article;blood smear;bone marrow biopsy;case report;ceruloplasmin blood level;clinical feature;copper blood level;copper deficiency/di [Diagnosis];cytopenia/di [Diagnosis];disease duration;disease exacerbation;drug megadose;drug withdrawal;dyserythropoiesis;erythrocyte count;ferritin blood level;folic acid blood level;hematological parameters;hemoglobin blood level;human;leukopenia;liver function test;low drug dose;male;mean corpuscular volume;myelodysplastic syndrome/di [Diagnosis];neutropenia/dt [Drug Therapy];pallor;partial thromboplastin time;petechia;physical examination;prothrombin time;purpura;red cell distribution width;refusal to participate;slit lamp;splenomegaly;treatment response;urinary excretion;vitamin blood level;vitamin supplementation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc blood level;antianemic agent/dt [Drug Therapy];anticonvulsive agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;cyanocobalamin/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];folic acid/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy],"Rau, A. R.;Usha, M.;Mallya, P.;Rau, A. T. K.",2014,01 Jan,http://dx.doi.org/10.1007/s12288-014-0456-3,0,0,
1409,Determination of the serum metallothionein (MT)1/2 concentration in patients with Wilson's disease and Menkes disease,"We have developed an easy and specific enzyme-linked immunoassay (ELISA) for the simultaneous determination of serum metallothinein-1 (MT-1) and 2 (MT-2) in both humans and experimental animals. A competitive ELISA was established using a specific polyclonal antibody against rat MT-2. The antibody used for this ELISA had exhibited the same cross-reactivity with MT in humans and experimental animals. The NH<inf>2</inf> terminal peptide of MT containing acetylated methionine was shown to be the epitope of this antibody. The reactivity of this ELISA system with the liver, kidney and brain in MT1/2 knock-out mice was significantly low, but was normal in an MT-3 knock-out mouse. The lowest detection limit of this ELISA was 0.6ng/ml and the spiked MT-1was fully recovered from the plasma.We investigated the normal range of MT1/2 (25-75%tile) in 200 healthy human serum and found it to be 27-48. ng/ml, and this was compared with the serum levels in various liver diseases. The serum MT1/2 levels in chronic hepatitis C (HCV) patients were significantly lower than healthy controls and also other liver diseases. In the chronic hepatitis cases, the MT1/I2 levels increased gradually, followed by the progression of the disease to liver cirrhosis and hepatocellular carcinoma. In particular, we found significantly elevated MT1/2 plasma levels in Wilson's disease patients, levels which were very similar to those in the Long-Evans Cinnamon (LEC) rat (model animal of Wilson's disease). Furthermore, a significantly elevated MT1/2 level was found in patients with Menkes disease, an inborn error of copper metabolism such as Wilson's disease. Copyright © 2014 Elsevier GmbH.",Liver disease;Long-Evans Cinnamon (LEC) rat;Menkes disease;Metallothionein 1/2;Wilson's disease;adult;alcohol liver disease;article;autoimmune hepatitis;ceruloplasmin blood level;child;clinical article;controlled study;copper blood level;cross reaction;disease course;enzyme linked immunosorbent assay;fatty liver;female;hepatitis C;human;immunoassay;Japan;liver cell carcinoma;liver fibrosis;male;Menkes syndrome/dt [Drug Therapy];primary biliary cirrhosis;protein blood level;Wilson disease/dt [Drug Therapy];zinc blood level;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];disulfiram/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];histidine/dt [Drug Therapy];metallothionein I/ec [Endogenous Compound];metallothionein II/ec [Endogenous Compound];polaprezinc/dt [Drug Therapy];zinc/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy],"Nakazato, K.;Tomioka, S.;Nakajima, K.;Saito, H.;Kato, M.;Kodaira, T.;Yatsuzuka, S. I.;Shimomura, Y.;Hiroki, T.;Motoyama, K.;Kodama, H.;Nagamine, T.",2014,,http://dx.doi.org/10.1016/j.jtemb.2014.07.013,0,0,
1410,Pathogenesis and management of wilson disease,"Hepatolenticular degeneration, commonly known as Wilson disease, is an autosomal recessive inherited disease of abnormal copper metabolism, characterized by the accumulation of copper in the body due to decreased biliary excretion of copper from hepatocytes. Wilson disease protein, ATP7B, functions in copper excretion into bile and in copper secretion to the bloodstream coupled with ceruloplasmin synthesis. Various kinds of mutations of ATP7B cause Wilson disease. Wilson disease is a rare genetic disease that can be treated pharmacologically. Recognition and prompt diagnosis are very important, because Wilson disease is fatal if left untreated. In this review, I summarize the pathogenesis and management of Wilson disease. © 2014 The Japan Society of Hepatology.",atp7b;Copper;Diagnosis;Treatment;Wilson disease;article;clinical feature;copper metabolism;diet;eye disease;genotype phenotype correlation;human;liver cell;liver cell carcinoma;liver disease;liver transplantation;mental disease;neurologic disease;pathogenesis;patient compliance;pregnancy;priority journal;prognosis;scoring system;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Harada, M.",2014,April,http://dx.doi.org/10.1111/hepr.12301,0,0,
1411,Treatment with d-penicillamine or zinc sulphate affects copper metabolism and improves but not normalizes antioxidant capacity parameters in Wilson disease,"Copper accumulation in tissues due to a biallelic pathogenic mutation of the gene: ATP7B results in a clinical phenotype known as Wilson disease (WD). Aberrations in copper homeostasis can create favourable conditions for superoxide-yielding redox cycling and oxidative tissue damage. Drugs used in WD treatment aim to remove accumulated copper and normalise the free copper concentration in the blood. In the current study the effect of decoppering treatment on copper metabolism and systemic antioxidant capacity parameters was analyzed. Treatment naive WD patients (TNWD) (n = 33), those treated with anti-copper drugs (TWD) (n = 99), and healthy controls (n = 99) were studied. Both TNWD and TWD patients characterised with decreased copper metabolism parameters, as well as decreased total antioxidant potential (AOP), glutathione (GSH) level, activity of catalase, glutathione peroxidase (GPx), and S-transferase glutathione, compared to controls. TWD patients had significantly lower copper metabolism parameters, higher total AOP and higher levels of GSH than TWD individuals; however, no difference was observed between these two patient groups with respect to the rest of the antioxidant capacity parameters. Patients who had undergone treatment with d-penicillamine or zinc sulphate did not differ with respect to copper metabolism or antioxidant capacity parameters, with the exception of GPx that was lower in d-penicillamine treated individuals. These data suggest that anti-copper treatment affects copper metabolism as well as improves, but does not normalize, natural antioxidant capacity in patients with WD. We propose to undertake studies aimed to evaluate the usefulness of antioxidants as well as selenium as a supplemental therapy in WD. © 2013 The Author(s).",Antioxidants;Copper;d-Penicillamine;Glutathione peroxidase;Oxidative stress;Treatment;Wilson disease;Zinc sulphate;adult;antioxidant activity;article;blood sampling;ceruloplasmin blood level;colorimetry;controlled study;copper blood level;copper metabolism;enzymatic assay;female;human;major clinical study;male;manganese blood level;middle aged;prospective study;treatment duration;Wilson disease/dt [Drug Therapy];young adult;catalase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];glutathione peroxidase/ec [Endogenous Compound];manganese superoxide dismutase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];transferase/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy];zinc sulfate/pd [Pharmacology],"Grazyna, G.;Agata, K.;Adam, P.;Tomasz, L.;Agata, W. C.;Karolina, D.;Grzegorz, C.;Anna, C.",2014,February,http://dx.doi.org/10.1007/s10534-013-9694-3,0,0,
1412,Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: Earlier administration of chelating therapy can reduce the damage to the brain,"The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 +/- 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started >= 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P =0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity. Copyright © 2014, Editorial Board of Neural Regeneration Research. All rights reserved.",Chelating therapy;Cirrhosis;Copper toxicity;Delayed diagnosis;Diagnostic imaging;Hepatic encephalopathy;Magnetic resonance imaging;Metabolic disorders;Nerve regeneration;Neural regeneration;Pontine myelinolysis;Wilson's disease;adult;article;brain damage/dt [Drug Therapy];caudate nucleus;central pontine myelinolysis;cerebellum disease;clinical article;degenerative disease;dystonic disorder;female;human;image analysis;latent period;male;mesencephalon;nuclear magnetic resonance imaging;parenchyma;parkinsonism;pons;putaminal hemorrhage;Wilson disease/di [Diagnosis];chelating agent/dt [Drug Therapy];penicillamine,"Kozic, D. B.;Petrovic, I.;Svetel, M.;Pekmezovic, T.;Ragaji, A.;Kostic, V. S.",2014,01 Nov,http://dx.doi.org/10.4103/1673-5374.145360,0,0,
1413,Long-term Outcome for Wilson Disease: 85% Good,,ceruloplasmin blood level;chronic liver failure;cohort analysis;editorial;follow up;fulminant hepatic failure;gene mutation;genetic screening;heart arrhythmia;hemochromatosis;human;infection;liver biopsy;liver cell carcinoma;liver cirrhosis;liver transplantation;long term care;maintenance therapy;overall survival;phenotype;sex difference;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy],"Schilsky, M. L.",2014,April,http://dx.doi.org/10.1016/j.cgh.2013.11.009,0,0,
1414,Prominent extensor truncal dystonia in egyptian patients with Wilson's disease,,"adolescent;adult;burke fahn marsden dystonia rating scale;clinical article;dysarthria;dystonia/dt [Drug Therapy];Egypt;extensor muscle;extensor truncal dystonia;fatality;female;generalized dystonia;human;interview;letter;male;medical record review;multifocal dystonia;named inventories, questionnaires and rating scales;neurologic examination;nuclear magnetic resonance imaging;palliative therapy;patient compliance;priority journal;rating scale;retrospective study;segmental dystonia;status dystonicus;trunk;videorecording;walking difficulty;Wilson disease/dt [Drug Therapy];young adult;baclofen;biperiden;penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy]","Shalash, A. S.;Elsayed, S. M.;Elnaghi, S.;Schneider, S. A.;Abdel Ghaffar, T. Y.",2014,January,http://dx.doi.org/10.1002/mds.25642,0,0,
1415,D-Penicillamine induced elastosis perforans serpiginosa with involvement of glans penis,"Elastosis perforans serpiginosa (EPS) is an unusual perforating disorder characterized by extrusion of altered elastic fibers through the epidermis. Clinically, it presents as keratotic papules with a tendency for serpiginous or annular distribution that most commonly involves the sides of the neck and the back. However, involvement of the penis has rarely been reported. We present a case of EPS involving the neck, axilla, and glans penis in a 42-year-old man who had received long-term d-penicillamine treatment for Wilson disease. Skin biopsy revealed perforating channels containing numerous altered elastic fibers, with a characteristic ""bramble brush"" or ""lumpy-bumpy"" appearance as demonstrated by an elastin stain. The latter is thought to be pathognomonic for penicillamine-induced degenerative elastosis. These degenerative changes occurring in glans penis have rarely been described in the literature. Prompt recognition of the rare presentation could lead to early discontinuation of the offending drug, to prevent further sequelae. © 2013, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.",d-penicillamine;elastosis perforans serpiginosa;glans penis;Wilson disease;acanthosis;adult;article;axilla;case report;clinical observation;cryotherapy;drug substitution;drug withdrawal;elastosis/di [Diagnosis];elastosis/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/si [Side Effect];follow up;histology;human;invagination;long term care;male;medical history;neck;papule;penis disease/di [Diagnosis];penis disease/si [Side Effect];penis glans;physical examination;rash;scar;skin biopsy;skin defect;skin irritation;stain;Wilson disease/dt [Drug Therapy];elastin;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine,"Chuang, Y. N.;Yao, C. A.;Chiu, T. M.;Yang, K. C.;Lin, Y. M.;Hsu, H. C.",2014,June,http://dx.doi.org/10.1016/j.dsi.2013.06.002,0,0,
1416,Wilson's disease: Hepatic manifestations,,acute hepatitis;acute liver failure;age distribution;alanine aminotransferase blood level;albumin dialysis;alkaline phosphatase blood level;ascites;aspartate aminotransferase blood level;autoimmune hepatitis;bile duct atresia;bilirubin blood level;breast feeding;breast milk;clinical feature;computer assisted tomography;decompensated liver cirrhosis;diagnosis;differential diagnosis;echography;elastography;fatty liver;fulminant hepatic failure;hemofiltration;hemolytic anemia;hepatic encephalopathy;histopathology;human;hypertransaminasemia;jaundice;kidney failure;laboratory test;liver biopsy;liver cell carcinoma;liver disease;liver function test;liver histology;liver transplantation;neurologic disease;nuclear magnetic resonance imaging;portal hypertension;pregnancy;primary biliary cirrhosis;primary sclerosing cholangitis;review;sex difference;splenomegaly;teratogenicity;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent;copper/ec [Endogenous Compound];penicillamine;trientine;zinc,"Shah, D.",2014,01 Sep,http://dx.doi.org/10.1016/j.disamonth.2014.07.004,0,0,
1417,Wilson's disease: Neurological and psychiatric manifestations,,anxiety;ataxia;bradykinesia;catatonia;chelation therapy;chorea;clinical feature;cognitive defect;depression;disease course;dysarthria;dystonia;gene mutation;human;impulsiveness;irritability;mania;mental disease;muscle rigidity;neurologic disease;nuclear magnetic resonance imaging;pathophysiology;personality disorder;prognosis;review;symptomatology;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Dalvi, A.",2014,01 Sep,http://dx.doi.org/10.1016/j.disamonth.2014.07.003,0,0,
1418,"Wilson's disease: Etiology, diagnosis, and treatment",,alcohol abstinence;anemia/si [Side Effect];autosomal recessive disorder;bone marrow suppression/si [Side Effect];cataract;ceruloplasmin blood level;clinical feature;Coombs test;copper blood level;copper metabolism;cornea disease;diet restriction;disease severity;drug cost;drug mechanism;dystonia/dt [Drug Therapy];early diagnosis;essential tremor/dt [Drug Therapy];follow up;fulminant hepatic failure/su [Surgery];gastrointestinal toxicity/si [Side Effect];gene mutation;hemolytic anemia;hemosiderosis/si [Side Effect];human;jaundice;Kayser Fleischer ring;laboratory test;liver biopsy;liver function test;liver toxicity;liver transplantation;lupus like syndrome/si [Side Effect];mental disease;neurologic disease;nuclear magnetic resonance imaging;onset age;parkinsonism/dt [Drug Therapy];patient monitoring;portal hypertension;practice guideline;review;slit lamp;tremor/dt [Drug Therapy];urinary excretion;vegetarian diet;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];baclofen/dt [Drug Therapy];benzodiazepine derivative/dt [Drug Therapy];ceruloplasmin;chelating agent/dt [Drug Therapy];chelating agent/po [Oral Drug Administration];cholinergic receptor blocking agent/dt [Drug Therapy];clonazepam/dt [Drug Therapy];copper;dimercaprol/ad [Drug Administration];dimercaprol/dt [Drug Therapy];dimercaprol/to [Drug Toxicity];dimercaprol/im [Intramuscular Drug Administration];dopamine receptor stimulating agent/dt [Drug Therapy];levodopa/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/an [Drug Analysis];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology];primidone/dt [Drug Therapy];propranolol/dt [Drug Therapy];rhodamine;tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trientine/pe [Pharmacoeconomics];trientine/pd [Pharmacology];trihexyphenidyl/dt [Drug Therapy];Wilson disease protein;zinc acetate/ae [Adverse Drug Reaction];zinc acetate/cm [Drug Comparison];zinc acetate/dt [Drug Therapy];zinc acetate/pd [Pharmacology];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy];zinc sulfate/pd [Pharmacology],"Dalvi, A.;Padmanaban, M.",2014,01 Sep,http://dx.doi.org/10.1016/j.disamonth.2014.07.002,0,0,
1419,Psychiatric aspects of Wilson disease: A review,"Objective: To review the current evidence about psychiatric symptoms in Wilson's disease (WD). Method: We searched Ovid, PsychInfo, CINHAL and PubMed databases from May 1946 to May 2012 using the key words Wilson('s) disease in combination with psychiatry, psychiatric, psychosis, schizophrenia, depression, mania, bipolar, mood, anxiety, personality and behavior. Results: Psychiatric symptoms occur before, concurrent with or after the diagnosis and treatment for WD. Thirty to forty percent of patients have psychiatric manifestations at the time of diagnosis, and 20% had seen a psychiatrist prior to their WD diagnosis. When psychiatric symptoms preceded neurological or hepatic involvement, the average time between the psychiatric symptoms and the diagnosis of WD was 864.3 days. The prevalence of psychiatric disorders in WD patients varies wildly (major depressive disorder, 4-47%; psychosis, 1.4-11.3%). Certain gene mutations of ATP7B may correlate with specific personality traits. Conclusions: Psychiatric manifestations represent a significant part of the clinical presentation of WD and can present at any point in the course of the illness. Psychiatric manifestations occurring without overt hepatic or neurologic involvement may lead to misdiagnosis. A better understanding of the psychiatric presentations in WD may provide insights into the underlying mechanisms of psychiatric disorders. © 2014 Elsevier Inc.",Ceruloplasmin;Copper;Psychiatry;Schizophrenia;Wilson's disease;adolescent;adult;anxiety;article;ATP7B gene;attention deficit disorder/dt [Drug Therapy];behavior disorder/dt [Drug Therapy];bipolar disorder;chelation therapy;child;clinical effectiveness;clinical feature;depression/dt [Drug Therapy];depression/th [Therapy];diagnostic error;electroconvulsive therapy;electroencephalography;female;gene mutation;generalized anxiety disorder/dt [Drug Therapy];genetic screening;human;laboratory test;liver disease;major clinical study;major depression/dt [Drug Therapy];major depression/th [Therapy];male;mania/dt [Drug Therapy];mental disease;middle aged;neuroimaging;neurologic disease;obsessive compulsive disorder/dt [Drug Therapy];personality;personality disorder/dt [Drug Therapy];preschool child;prevalence;psychosis/dt [Drug Therapy];psychotherapy;schizophrenia/dt [Drug Therapy];schizophrenia/th [Therapy];school child;suicide attempt/dt [Drug Therapy];Wilson disease;young adult;alprazolam/dt [Drug Therapy];amitriptyline/dt [Drug Therapy];antiparkinson agent/dt [Drug Therapy];biperiden/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chlorpromazine/dt [Drug Therapy];clomipramine/dt [Drug Therapy];copper/ec [Endogenous Compound];fluoxetine/dt [Drug Therapy];haloperidol/dt [Drug Therapy];lithium/dt [Drug Therapy];lorazepam/dt [Drug Therapy];mianserin/dt [Drug Therapy];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];perphenazine/dt [Drug Therapy];pipamperone/dt [Drug Therapy];risperidone/dt [Drug Therapy];serotonin/ec [Endogenous Compound];serotonin uptake inhibitor/dt [Drug Therapy];thioridazine/dt [Drug Therapy];tricyclic antidepressant agent/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];unindexed drug;valproate semisodium/dt [Drug Therapy];valproic acid/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy];zuclopenthixol/dt [Drug Therapy],"Zimbrean, P. C.;Schilsky, M. L.",2014,January,http://dx.doi.org/10.1016/j.genhosppsych.2013.08.007,0,0,
1420,Plasma exchange for hemolytic crisis and acute liver failure in Wilson disease,"Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible. © 2013 Dr. K C Chaudhuri Foundation.",Acute liver failure;Copper;Hemolysis;Plasma exchange;Wilson disease;acute kidney failure;article;case report;chelation therapy;child;copper blood level;female;hemolytic anemia;hospitalization;human;liver transplantation;plasmapheresis;preschool child;copper complex;penicillamine/po [Oral Drug Administration];zinc/po [Oral Drug Administration],"Verma, N.;Pai, G.;Hari, P.;Lodha, R.",2014,May,http://dx.doi.org/10.1007/s12098-013-0979-x,0,0,
1421,Modes of drug elimination and bioactive metabolites,"Drug elimination is the removal of active drug from the body. Metabolism takes place largely in the liver and produces water soluble metabolites which can be excreted in the bile or urine. Metabolism may also produce active or toxic metabolites or a pharmacologically active drug from an inactive prodrug. Most volatile anaesthetics are excreted unchanged via the lungs. Drug elimination can be affected by factors such as first-pass metabolism, genetic variants and various disease processes. Knowledge of these processes will allow better prediction of pharmacokinetics in practice. © 2014 Elsevier Ltd. All rights reserved.",Clearance;excretion;metabolism;pharmacokinetics;acetylation;article;biliary excretion;breast milk;chelation;chronic kidney failure;creatinine blood level;dialysis;drug bioavailability;drug blood level;drug clearance;drug conjugation;drug elimination;drug mechanism;drug response;enzyme deficiency;first pass effect;genetic variability;glomerulus filtration rate;glucose 6 phosphate dehydrogenase deficiency;hair;heart failure;hemochromatosis;hemolysis;heredity;human;hydrolysis;iron chelation;kidney clearance;kidney tubule absorption;kidney tubule excretion;lacrimal fluid;liver blood flow;liver cell;liver clearance;liver disease;lung clearance;neuromuscular blocking;oxidation;oxidation reduction reaction;priority journal;pseudocholinesterase deficiency;saliva;skin;sweat;systemic circulation;urinary excretion;Wilson disease;acetylsalicylic acid;anesthetic agent/pk [Pharmacokinetics];arsenic;atracurium besilate;cholinesterase/ec [Endogenous Compound];copper;creatinine/ec [Endogenous Compound];deferoxamine;drug metabolite;glucose 6 phosphate dehydrogenase/ec [Endogenous Compound];glyceryl trinitrate;hydralazine;isoniazid;lead;lidocaine;mercury;morphine;morphine 6 glucuronide;pancuronium;penicillamine;quinolone derivative;remifentanil;rocuronium;salazosulfapyridine;salbutamol;sugammadex;sulfonamide;suxamethonium;toxin;vecuronium,"Chillistone, S.;Hardman, J. G.",2014,August,http://dx.doi.org/10.1016/j.mpaic.2014.04.024,0,0,
1422,Persistent hepatic encephalopathy secondary to portosystemic shunt occluded with Amplatzer device,"Hepatic encephalopathy is a frequent complication of cirrhosis, when this event becomes persistent, treatment compliance should be verified and any precipitating factor need to be identified. Also the presence of portosystemic shunts, which are a rare cause of decompensation or persistence hepatic encephalopathy need to be ruled out. In this paper we report the case of a 57 year old man with persistent hepatic encephalopathy secondary to the presence of a porto-onfalo-femoral shunt successfully closed with the placement of an Amplatzer device.",Amplatzer Vascular Plug II;Cirrhosis;Encephalopathy recurrent;Spontaneous shunt;adult;alanine aminotransferase blood level;alkaline phosphatase blood level;ammonia blood level;Amplatzer vascular plug;article;aspartate aminotransferase blood level;asthenia;case report;Child Pugh score;computer assisted tomography;differential diagnosis;disease course;disease severity;endoscopy;esophagus varices/di [Diagnosis];fatty liver/di [Diagnosis];follow up;hemochromatosis/di [Diagnosis];hepatic encephalopathy/co [Complication];hepatic encephalopathy/di [Diagnosis];hepatic encephalopathy/dt [Drug Therapy];hepatography;hospital discharge;human;human tissue;liver biopsy;liver cirrhosis/di [Diagnosis];liver function test;male;Model For End Stage Liver Disease Score;phlebography;portosystemic anastomosis;rehydration;treatment response;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];aspartic acid/dt [Drug Therapy];gamma glutamyltransferase/ec [Endogenous Compound];lactulose/dt [Drug Therapy];magnesium/dt [Drug Therapy];ornithine/dt [Drug Therapy];rifaximin/dt [Drug Therapy];zinc/dt [Drug Therapy],"Ramirez-Polo, A.;Marquez-Guillen, E.;Gonzalez-Aguirre, A. J.;Casanova-Sanchez, I. E.;Chavez-Ruiz, R.;Carrillo-Maravilla, E.;Lopez-Mendez, E.",2014,July - August,,0,0,
1423,Design of intrahepatocyte copper(I) chelators as drug candidates for Wilson's disease,"Wilson's disease is an autosomal recessive disease caused by mutations on the ATP7B gene found on chromosome 13. Since the corresponding ATPase is in charge of copper (Cu) distribution and excretion in the liver, its malfunctioning leads to Cu overload. This short review deals with treatments of this rare disease, which aim at decreasing Cu toxicity and are, therefore, based on chelation therapy. The drugs used since the 1950s are described first, then a novel approach developed in our laboratory is presented. Since the liver is the main organ of Cu distribution in the body, we targeted the pool of intracellular Cu in hepatocytes. This Cu pool is in the +1 oxidation state, and therefore soft sulfur ligands inspired from binding sites found in metallothioneins were developed. Their targeting to the hepatocytes by functionalization with ligands of the asialoglycoprotein receptor led to their cellular incorporation and intracellular Cu chelation. © 2014 New York Academy of Sciences.",Copper(I);Hepatic cells;Sulfur ligands;Wilson's disease;article;binding affinity;binding site;chelation therapy;complex formation;drug design;drug structure;drug targeting;homeostasis;human;ligand binding;liver cell;oxidation;Wilson disease/dt [Drug Therapy];chelating agent/dv [Drug Development];chelating agent/dt [Drug Therapy];cuprous ion/dv [Drug Development];cuprous ion/dt [Drug Therapy];lewisite/dt [Drug Therapy];metallothionein;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy],"Gateau, C.;Delangle, P.",2014,May,http://dx.doi.org/10.1111/nyas.12379,0,0,
1424,Treatment of Wilson's disease motor complications with deep brain stimulation,"A considerable proportion of patients with Wilson's disease (WD) experience neurologic symptoms that are functionally disabling. The most common neurologic problems in advanced WD include dystonia and tremor. Medically refractory idiopathic dystonia and essential tremor (ET) have been successfully treated with deep brain stimulation (DBS), functional surgical therapy targeting the globus pallidus pars interna (GPi), or the ventral intermediate (Vim) thalamic nucleus. Even though the pathophysiology of tremor is different in WD and ET, available experience supports DBS targeting the Vim for WD patients. Dystonia associated with WD is classified as secondary dystonia and GPi stimulation has yielded mixed results in these patients. The presence of structural changes in the basal ganglia may limit the therapeutic success of DBS for WD dystonia compared with idiopathic dystonia. In spite of these limitations, DBS in WD may be an effective approach to treat medically refractory residual neurologic symptoms in carefully selected patients. © 2014 New York Academy of Sciences.",Deep brain stimulation;Dystonia;Internal globus pallidus;Tremor;Ventral intermediate thalamic nucleus;Wilson's disease;ADL disability;article;basal ganglion;brain depth stimulation;chelation therapy;computer assisted tomography;dystonia/th [Therapy];electrode;flapping tremor/th [Therapy];generalized dystonia/th [Therapy];globus pallidus;human;motor dysfunction/th [Therapy];nuclear magnetic resonance imaging;pallidotomy;Parkinson disease;pathophysiology;phenotype;radiosurgery;segmental dystonia/th [Therapy];subthalamic nucleus;thalamotomy;thalamus anterior nucleus;thalamus ventral nucleus;tremor/th [Therapy];Wilson disease;zona incerta;benzodiazepine;botulinum toxin;clonazepam;penicillamine;pregabalin;topiramate;trientine,"Hedera, P.",2014,May,http://dx.doi.org/10.1111/nyas.12372,0,0,
1425,Hepatobiliary quiz-9 (2014),,acute hepatitis;article;chronic hepatitis;deceased liver donor;disease exacerbation;ferritin blood level;graft survival;hemochromatosis/cn [Congenital Disorder];hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];hemochromatosis/th [Therapy];hepatitis B;hepatobiliary disease;histopathology;human;iron overload;kayser fleischer ring;liver hemosiderosis;liver transplantation;Model For End Stage Liver Disease Score;neonatal hemochromatosis/cn [Congenital Disorder];neonatal hemochromatosis/di [Diagnosis];neonatal hemochromatosis/et [Etiology];neonatal hemochromatosis/th [Therapy];organ donor;overall survival;plasmapheresis;priority journal;survival rate;virus reactivation;visual system parameters;Wilson disease/dt [Drug Therapy];alpha fetoprotein/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hepatitis B core antibody/ec [Endogenous Compound];hepatitis B surface antigen/ec [Endogenous Compound];hepatitis B(e) antigen/ec [Endogenous Compound];immunoglobulin G/ec [Endogenous Compound];immunoglobulin M/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];transferrin/ec [Endogenous Compound];trientine/dt [Drug Therapy];virus DNA/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Agrawal, S.;Dhiman, R. K.",2014,March,http://dx.doi.org/10.1016/j.jceh.2014.03.054,0,0,
1426,Multiple sclerosis in two patients with coexisting Wilson's disease,"Wilson's disease (WD) is an inherited disorder of copper metabolism with main hepatic and neurological symptoms. Multiple sclerosis (MS) is an autoimmune and inflammatory demyelinating disease. We present two patients with coexisting WD and MS. In both cases the diagnosis of MS preceded diagnosis of WD. Both patients exhibited neurological signs typical of MS (internuclear palsy, optic neuritis). The first one displayed typical signs of WD (hypomimia, sialorrhea, behavioral changes). The second patient had liver injury without any neurological symptoms. In both cases clinical course of MS was very mild (17 and 12 years of observation) which may be caused by immunosuppressive effect of free copper. © 2013 Elsevier B.V. All rights reserved.",Coexistence;D-penicillamine;Free copper;Multiple sclerosis;Wilson's disease;Zinc sulfate;acute liver failure;adiadochokinesis;adult;article;ascites;ataxic gait;ATP7B gene;behavior disorder;brain damage/di [Diagnosis];case report;ceruloplasmin blood level;clinical feature;copper blood level;copper metabolism;corpus callosum;disease course;drug withdrawal;dysarthria;enzyme defect/si [Side Effect];faintness;female;follow up;gene;gene mutation;hand tremor;head injury;hepatitis;histopathology;human;human tissue;hypersalivation;hypomimia;jaundice;liver fibrosis;liver level;male;medical history;motor dysfunction;multiple sclerosis/di [Diagnosis];nonhuman;nuclear magnetic resonance imaging;ophthalmoplegia;optic neuritis/dt [Drug Therapy];protein cerebrospinal fluid level;treatment response;urinary excretion;white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];beta interferon/ae [Adverse Drug Reaction];beta interferon/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];oligoclonal band/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy],"Dziezyc, K.;Litwin, T.;Czlonkowska, A.",2014,May,http://dx.doi.org/10.1016/j.msard.2013.09.002,0,0,
1427,Therapies for ataxias,"Ataxia can originate from many genetic defects, but also from nongenetic causes. To be able to provide treatment, the first step is to establish the right diagnosis. Once the cause of the ataxia is defined, some specific treatments may be available. For example, the nongenetic ataxias that arise from vitamin deficiencies can improve following treatment. In most cases, however, therapies do not cure the disease and are purely symptomatic. Physiotherapy and occupational therapy are effective in all type of ataxias and often remain the most efficient treatment option for these patients to maximize their quality of life. © Springer Science+Business Media 2014.",Ataxia;Ataxia-telangiectasia;aved;Cerebrotendinous xanthomatosis;Copper deficiency;Episodic ataxia;Folate deficiency;Friedreich's ataxia;Niemann pick disease;Refsum's disease;sca;Vitamin b12 deficiency;Wernicke's encephalopathy;Wilson's disease;alpha tocopherol deficiency;article;ataxia/rh [Rehabilitation];ataxia telangiectasia;ataxia with vitamin E deficiency;autosomal dominant disorder;autosomal dominant inheritance;autosomal recessive disorder;diagnostic procedure;drug efficacy;exercise;Friedreich ataxia;gait;gene expression;gene mutation;gene therapy;hepatocyte transplantation;human;Machado Joseph disease;muscle training;neurologic disease;nonhuman;occupational therapy;oxidative stress;peripheral neuropathy;physiotherapy;plasmapheresis;prognosis;quality of life;randomized controlled trial (topic);Refsum disease;symptom;therapy effect;treatment indication;vitamin deficiency;vitamin supplementation;Wilson disease;4 aminopyridine;adenosine A2a receptor agonist;alpha tocopherol;amantadine;antioxidant;ataxin 3/ec [Endogenous Compound];ATM protein/ec [Endogenous Compound];betamethasone;carnitine;chenodeoxycholic acid;cholestanetriol 26 monooxygenase/ec [Endogenous Compound];cholestanol/ec [Endogenous Compound];deferiprone;estradiol;frataxin/ec [Endogenous Compound];glycosphingolipid/ec [Endogenous Compound];histone deacetylase inhibitor;idebenone;lithium carbonate;methylene blue;miglustat;penicillamine;phytanic acid;recombinant erythropoietin;riluzole;trientine;ubidecarenone;unindexed drug;varenicline;zinc derivative,"Martineau, L.;Noreau, A.;Dupre, N.",2014,July,http://dx.doi.org/10.1007/s11940-014-0300-y,0,0,
1428,Copper ring around cornea,,adult;article;case report;cornea;drug substitution;drug withdrawal;female;follow up;human;kayser fleischer ring/di [Diagnosis];liver function test;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/to [Drug Toxicity];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],Anonymous,2014,,,0,0,
1429,Wilson disease. [Czech],"Wilson's disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilson's disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilson's disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The diagnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, Kayser-Fleischer ring). The diagnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilson's disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc are used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.",D-penicillamine;Treatment;Wilson's disease;Zinc;acute hepatitis;article;chronic hepatitis;dysarthria;Europe;extrapyramidal syndrome;fulminant hepatic failure;gene mutation;genetic disorder;human;liver cirrhosis;liver graft;motor dysfunction;muscle contraction;steatosis;survival rate;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Marecek, Z.;Bruha, R.",2014,,,0,0,
1430,Effect of molecular adsorbents recirculating system treatment in children with acute liver failure caused by wilson disease,"OBJECTIVES: Because fulminant Wilson disease (WD) has an extremely poor prognosis, the use of liver support that can bridge patients to liver transplantation is lifesaving. We report the experience of albumin dialysis in acute liver failure (ALF) caused by WD in children. METHODS: Chart review of children admitted for ALF secondary to acute WD and treated by the molecular adsorbents and recirculating system. Measures of copper level in blood and within the circuit during molecular adsorbents recirculating system (MARS) sessions were performed. Clinical and biological assessments after MARS session were reported. RESULTS: Four children, with a median age of 12.3 years, were treated from 2004 to 2009 for a severe ALF associated with acute renal failure, haemolysis, and severe cholestasis. All of the children had a new Wilson index >12. A total of 14 MARS sessions were performed, for a median duration of 7.5 hours. Tolerance was good, except for 1 child who experienced haemorrhage because of vascular injury following insertion of the dialysis catheter. A neurological improvement or stabilisation was noted in all of the children along with an improvement in the Fisher index and ammonia level after MARS treatment. MARS was able to remove copper, to decrease the serum copper level of 28% in mean, and to decrease the bilirubin and creatinin levels >25%. All of the children were subsequently underwent liver transplants with a good outcome without disability. CONCLUSIONS: MARS is able to remove copper and to stabilise children with ALF secondary to WD, allowing bridging to LT. Copyright © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.",acute liver failure;albumin dialysis;artificial liver support;molecular adsorbents and recirculating system;Wilson disease;acute kidney failure;acute liver failure/co [Complication];acute liver failure/su [Surgery];acute liver failure/th [Therapy];adolescent;adverse outcome;article;bilirubin blood level;bleeding/co [Complication];blood vessel injury/co [Complication];case report;child;cholestasis;clinical assessment;copper blood level;creatinine blood level;dialysis catheter;disease severity;female;hemodialysis machine;hemofiltration;hemolysis;human;liver function;liver transplantation;machine;male;medical record review;priority journal;school child;treatment outcome;Wilson disease/dt [Drug Therapy];albumin;bilirubin/ec [Endogenous Compound];copper;creatinine/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Rustom, N.;Bost, M.;Cour-Andlauer, F.;Lachaux, A.;Brunet, A. S.;Boillot, O.;Bordet, F.;Valla, F.;Richard, N.;Javouhey, E.",2014,February,http://dx.doi.org/10.1097/MPG.0b013e3182a853a3,0,0,
1431,ISMP adverse drug reactions : Recurrent small intestinal ileus due to valsartan; compulsive behaviors related to rasagiline use; lacosamide-induced acute pancreatitis; brief psychotic disorder after abrupt withdrawal of hydroxyzine; hydroxyurea-associated acral erythema; penicillamine-induced degenerative dermatosis,"The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). Copyright © 2014 Thomas Land Publishers, Inc.",abdominal distension;abdominal pain/si [Side Effect];abdominal tenderness;acute pancreatitis/dt [Drug Therapy];add on therapy;adult;adverse drug reaction;aged;agitation;anxiety;article;brief psychotic disorder/si [Side Effect];cholangiography;clinical article;colonoscopy;compulsion/dt [Drug Therapy];compulsion/si [Side Effect];computer assisted tomography;conservative treatment;constipation;cutis laxa;degenerative dermatosis/si [Side Effect];epigastric pain;erectile dysfunction;erythema/si [Side Effect];female;fibromyalgia/dt [Drug Therapy];gastrointestinal symptom;hospital admission;human;hypercholesterolemia;hypertension;ileus;intestine sound;laboratory test;laparotomy;male;middle aged;nausea;nuclear magnetic resonance imaging;Parkinson disease/dt [Drug Therapy];physical examination;physician;push enteroscopy;remission;skin disease/si [Side Effect];small intestine obstruction/si [Side Effect];vomiting;Wilson disease/dt [Drug Therapy];Yale Brown Obsessive Compulsive Scale;alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];amylase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];C reactive protein/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];haloperidol;harkoseride/dt [Drug Therapy];hydroxyurea/ae [Adverse Drug Reaction];hydroxyzine/ae [Adverse Drug Reaction];infusion fluid;lorazepam;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];pravastatin;rasagiline/ae [Adverse Drug Reaction];rasagiline/dt [Drug Therapy];ropinirole/dt [Drug Therapy];sertraline/dt [Drug Therapy];valsartan/ae [Adverse Drug Reaction],"Mancano, M.",2014,01 Nov,http://dx.doi.org/10.1310/hpj4910-902,0,0,
1432,Treatment of Wilson's disease: Our patients deserve better,,Copper;Penicillamine;Trientine;Wilson's disease;Zinc;acute liver failure;coordination disorder;dystonia;gene mutation;health care quality;hepatitis;human;liver cirrhosis;maintenance therapy;motor dysfunction;recurrent disease;review;tremor;Wilson disease/dt [Drug Therapy];work experience;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Brewer, G. J.",2014,01 Dec,http://dx.doi.org/10.1517/21678707.2014.975207,0,0,
1433,The effect of zinc and D-penicillamine in a stable human hepatoma ATP7B knockout cell line,"Mutations in the copper (Cu) transporter gene ATP7B, the primary cause of Wilson disease (WD), result in high liver Cu and death of hepatocytes. Cu chelators and zinc salts are the two most important drugs used in the treatment of WD patients; however, the molecular mechanisms of the drugs with regard to ATP7B expression have not been determined. A targeted knockout of ATP7B (KO) was established in the most widely used human hepatoma cell line, HepG2 for molecular studies of the pathogenesis and treatment of the disease. KO cells showed similar growth, Cu uptake, release, and gene expression as compared to parental cells. However, in the presence of Cu, morphological changes, oxidative stress, apoptosis, and loss of viability were observed. Induction of metallothionein (MT1X) after Cu exposure was significantly reduced in KO cells. Following zinc treatment, MT1X expression was strongly induced and a high percentage of KO cells could be rescued from Cu induced toxicity. D-penicillamine treatment had a minor effect on the viability of KO cells whereas the parental cell line showed a pronounced improvement. Combined treatment displayed a highly synergistic effect in KO cells. The data suggest that zinc has a previously unrecognized effect on the viability of hepatocytes that lack ATP7B due to a high induction of MT1X expression that compensates low gene expression after Cu exposure. A combination therapy that simultaneously targets at MT1X induction and Cu chelation improves the overall survival of hepatocytes for most efficient therapy of patients having WD. © 2014 Chandhok et al.",apoptosis;article;bioaccumulation;cell structure;cell survival;cell viability;concentration response;controlled study;copper metabolism;cytotoxicity;enzyme induction;hepatocellular carcinoma cell line;human;human cell;oxidative stress;protein expression;real time polymerase chain reaction;Western blotting;metallothionein/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/pd [Pharmacology];zinc/cb [Drug Combination];zinc/pd [Pharmacology],"Chandhok, G.;Schmitt, N.;Sauer, V.;Aggarwal, A.;Bhatt, M.;Schmidt, H. H. J.",2014,03 Jun,http://dx.doi.org/10.1371/journal.pone.0098809,0,0,
1434,"Zinc mono-therapy in pre-symptomatic chinese children with Wilson Disease: A single center, retrospective study","Background: There is no official consensus regarding zinc therapy in pre-symptomatic children with Wilson Disease (WD); more data is needed. Objective: To investigate the safety and efficacy of zinc gluconate therapy for Chinese children with pre-symptomatic WD. Methods: We retrospectively analyzed pre-symptomatic children receiving zinc gluconate in a single Chinese center specialized in pediatric hepatology. Short-term follow-up data on safety and efficacy were presented, and effects of different zinc dosages were compared. Results: 30 children (21 males) aged 2.7 to 16.8 years were followed for up to 4.4 years; 26 (87%) children had abnormal ALT at baseline. Most patients (73%) received higher than the currently recommended dose of elemental zinc. Zinc gluconate significantly reduced mean ALT (p<0.0001), AST (p<0.0001), GGT (p<0.0001) levels after 1 month, and urinary copper excretion after 6 months (p<0.0054). Mean direct bilirubin levels dropped significantly at 1 month (p = 0.0175), 3 months (p = 0.0010), and 6 months (p = 0.0036). Serum zinc levels gradually increased and reached a significantly higher level after 6 months (p<0.0026), reflecting good compliance with the therapy. Complete blood count parameters did not change throughout the analysis period. 8 children experienced mild and transient gastrointestinal side effects. The higher zinc dose did not affect treatment response and was not associated with different or increased side effects when compared to conventional zinc dose. Conclusion: In our cohort, zinc gluconate therapy for Chinese children with pre-symptomatic WD was effective, and higher initial dose of elemental zinc had the same level of efficacy as the conventional dose. © 2014 Abuduxikuer, Wang.",abdominal discomfort/si [Side Effect];abdominal pain/si [Side Effect];adolescent;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;bilirubin blood level;blood cell count;child;Chinese;clinical article;controlled study;copper metabolism;diarrhea/si [Side Effect];dose response;drug dose comparison;drug dose increase;drug dose reduction;drug efficacy;drug megadose;drug safety;drug substitution;drug withdrawal;epigastric pain/si [Side Effect];female;fever/si [Side Effect];gamma glutamyl transferase blood level;gastrointestinal symptom/si [Side Effect];hematuria/si [Side Effect];human;male;monotherapy;patient compliance;preschool child;proteinuria/si [Side Effect];retrospective study;school child;vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];zinc blood level;alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];gluconate zinc/ae [Adverse Drug Reaction];gluconate zinc/do [Drug Dose];gluconate zinc/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Abuduxikuer, K.;Wang, J. S.",2014,24 Jan,http://dx.doi.org/10.1371/journal.pone.0086168,0,0,
1435,Acute lymphoblastic leukemia in a girl with Wilson's disease,"Wilson's disease (WD) is an autosomal recessive defect in cellular copper transportation. Although acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy, only two cases of ALL associated with WD have been reported to date. One patient died of relapse and infection, and the other died of neutropenic sepsis during the treatment. We here describe the case of a 10-year-old girl with WD and ALL. Adverse events of chemotherapy, including liver toxicity and severe myelosuppression, necessitated adjustments in the chemotherapy doses. After completion of the treatment, the patient has remained in remission from ALL without progression of liver damage for 2 years. Severe treatment-related toxicity should be considered in chemotherapy for patients with WD. Copyright © 2014 Japan Pediatric Society.",atp7b;D-penicillamine;Glutathione-S-transferase;Liver toxicity;Zinc acetate;acute lymphoblastic leukemia/di [Diagnosis];acute lymphoblastic leukemia/dt [Drug Therapy];acute lymphoblastic leukemia/th [Therapy];alanine aminotransferase blood level;article;aspartate aminotransferase blood level;bilirubin blood level;bone marrow biopsy;bone marrow suppression/co [Complication];cancer regression;case report;child;Child Pugh score;copper blood level;creatinine blood level;disease association;drug dose escalation;drug dose increase;drug dose reduction;drug megadose;drug substitution;drug withdrawal;febrile neutropenia/si [Side Effect];female;follow up;hemoglobin blood level;human;hyperbilirubinemia/si [Side Effect];hypertransaminasemia/si [Side Effect];hyponatremia/si [Side Effect];induction chemotherapy;kidney tubule disorder;laboratory test;leukemia remission;leukocyte count;liver nodule/di [Diagnosis];liver toxicity/co [Complication];pancytopenia/co [Complication];pancytopenia/si [Side Effect];portal hypertension/di [Diagnosis];pre B lymphocyte;priority journal;prothrombin time;school child;treatment duration;vasopressin release;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];zinc blood level;alanine aminotransferase/ec [Endogenous Compound];asparaginase/ae [Adverse Drug Reaction];asparaginase/cb [Drug Combination];asparaginase/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];cyclophosphamide/ae [Adverse Drug Reaction];cyclophosphamide/cb [Drug Combination];cyclophosphamide/dt [Drug Therapy];cytarabine/ae [Adverse Drug Reaction];cytarabine/tl [Intrathecal Drug Administration];daunorubicin/ae [Adverse Drug Reaction];daunorubicin/cb [Drug Combination];daunorubicin/dt [Drug Therapy];dexamethasone/ae [Adverse Drug Reaction];dexamethasone/cb [Drug Combination];dexamethasone/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];hydrocortisone/ae [Adverse Drug Reaction];hydrocortisone/tl [Intrathecal Drug Administration];methotrexate/ae [Adverse Drug Reaction];methotrexate/tl [Intrathecal Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prednisolone/ae [Adverse Drug Reaction];prednisolone/cb [Drug Combination];prednisolone/dt [Drug Therapy];vincristine/ae [Adverse Drug Reaction];vincristine/cb [Drug Combination];vincristine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Maeda, S.;Matsubara, H.;Hiejima, E.;Tanaka, A.;Okada, M.;Kato, I.;Umeda, K.;Hiramatsu, H.;Watanabe, K. I.;Heike, T.;Adachi, S.",2014,,http://dx.doi.org/10.1111/ped.12313,0,0,
1436,The Pragmatic Treatment of Wilson's Disease,"Wilson's disease (WD) is a potentially fatal disorder of chronic copper toxicity, primarily affecting the liver and the brain. Judicious treatment can restore health and longevity, even in patients with severe neurological impairment. However, the disease is associated with considerable morbidity and mortality resulting from delay in diagnosis, and difficulty in pacing the medical treatment. In this article, we briefly review the diagnosis and treatment options for WD and share our experience in managing patients with WD. We focus on decoppering (copper chelation) treatment of WD and outline pragmatic strategies for patient management designed to recognize and minimize adverse effects while ensuring treatment compliance and effectiveness. Copyright © 2014 International Parkinson and Movement Disorder Society.",GAS for WD;Penicillamine;Trientine;article;brain;ceruloplasmin blood level;chelation therapy;decoppering;drug bioavailability;drug induced disease;gene mutation;gene sequence;human;liver;monotherapy;mutational analysis;nuclear magnetic resonance imaging;priority journal;rash;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;dimercaprol/dt [Drug Therapy];lithium/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Aggarwal, A.;Bhatt, M.",2014,April 01,http://dx.doi.org/10.1002/mdc3.12003,0,0,
1437,Wilson-Konovalov disease in 3 sisters: A radical change in prognosis if timely diagnosed. [Russian],"Wilson-Konovalov disease is a rare autosomal recessive genetic disorder in which copper accumulates in the liver, brain and other target organs. The paper describes a family case of the abdominal form of the disease in three sisters, the eldest of them died from fulminant liver failure at the age of 18 years. The second sister aged 16 years was diagnosed as having the disease at the stage of decompensated liver cirrhosis; her treatment with D-penicillamine resulted in complete disease remission. The youngest sister was diagnosed with the disease at the preclinical stage, which could expect its good prognosis. However, the patient's refusal of treatment led to death from liver failure. This case demonstrates the importance of timely diagnosis and the possibility of dramatic improvement in prognosis even at the stage of decompensated liver cirrhosis.",acute liver failure/di [Diagnosis];acute liver failure/et [Etiology];adult;article;case report;early diagnosis;fatality;female;human;liver cirrhosis/di [Diagnosis];liver cirrhosis/dt [Drug Therapy];liver cirrhosis/et [Etiology];pedigree;prognosis;sibling;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult,"Rozina, T. P.;Ignatova, T. M.;Solovyeva, O. V.",2014,,,0,0,
1438,Long-term observation of wilson disease patients-experience of a single center,"INTRODUCTION: Wilson disease (WD) is an inherited copper metabolism disorder. If the patient remains undiagnosed and untreated, disease outcome may be fatal. Lifelong therapy provides normal WD patients' survival. AIMS & METHODS: Aim: To evaluate the clinical course and long-term outcome of WD patients. Material and methods: Sixty-five WD patients (22 females and 43 males) at a mean age of 37 years (range, 18-65 years) were analysed from January, 2003 to December, 2013. Survival analysis by Kaplan-Meier method and Logit model were used. RESULTS: Twenty-eight patients (43.08%) were with liver disease alone, thirtytwo (49.23%) - with hepatic and neurological presentation, three - with neurological features without any signs of a liver injury. There were two asymptomatic patients, too. The following hepatic forms were proved: steatosis (in 6.6%), hepatitis (in 41.7%), and cirrhosis (in 51.7% of the patients). There was a mean delay of diagnosis of 39 months. At the end of the study, 74.2% of cirrhotic patients were in Child A stage. Two patients developed acute liver failure after treatment discontinuation. We observed a hepatocellular carcinoma in one cirrhotic patient. Six patients with liver cirrhosis of Child C stage had fatal outcome during the observation. Three of them were with concurrent diseases - HBV and autoimmune cirrhosis. Kayser-Fleischer ring was detected in 35.4% of the patients being more common in those presenting with neurological symptoms. The cumulative survival rate of people with WD after first onset of symptoms was up to 76.38% at the end of 15th year, and that after diagnosis - 77.29%. It was estimated the impact of the lag in the diagnosis of WD on overall survival. At each year delay in the diagnosis the probability of death was increased by approximately 10%. There was a beneficial effect of D-penicillamine (D-p) treatment in almost all the patients. There were no complications during the pregnancies, with stable disease and normal birth. CONCLUSION: Our observation showed a delayed diagnosis of WD. In most patients, the course of the disease was stable or even improved during the treatment. Mortality rate increased in the patients with cirrhosis. There was a favourable response after long-term treatment with D-p as first-line therapy in WD.",Wilson disease;patient;human;European;gastroenterology;female;liver cirrhosis;diagnosis;therapy;child;survival;hepatitis;steatosis;liver injury;liver cell carcinoma;metabolic disorder;diseases;survival rate;overall survival;copper metabolism;liver disease;model;acute liver failure;Kaplan Meier method;disease course;fatality;male;neurologic disease;mortality;death;delayed diagnosis;pregnancy;long term care;penicillamine,"Gancheva, D.;Kotzev, I.;Kaneva, M.;Kaprelyan, A.;Grudkova, M.",2014,October,http://dx.doi.org/10.1177/2050640614548980,0,0,
1439,Improvement in the severity of pulmonary arterial hypertension in a patient receiving copper-chelating therapy,"Introduction: Pulmonary arterial hypertension (PAH) is a chronic, debilitating and progressive disease leading to premature death, frequently due to right ventricular (RV) failure. The pathobiology of severe PAH is based on the formation of angioproliferative lung lesions leading to obstruction of blood flow. Recent experimental studies show that copper is necessary for the formation of the lesions, and that copper chelation can prevent and even revert the lesions. Tetrathiomolybdate is a highly effective copper chelator that is being used to treat Wilson's disease and has been used to treat therapy refractory malignancies. Case report: We hereby report the experience of using tetrathiomolybdate (ATN-224) for copper chelation in a patient who has been diagnosed with idiopathic PAH 3 years ago. A 59 year old female with significant symptoms due to exertional dyspnea and fatigue (New York Association Class III), despite treatment with amlodipine, bosentan and sildenafil was evaluated with a 6-minute walk test (417 m), cardiac catheterization (systolic and mean pulmonary arterial pressure of 58/24 and 32 mmHg and pulmonary vascular resistance of 4.6 wood units), Doppler echocardiogram (showing systolic pulmonary arterial pressure of 73 mmHg), and cardiac magnetic resonance (RV ejection fraction 48% and stroke volume 75 ml). She was then started on ATN-224 (dose 150mg twice daily) which she continued for 16 days before stopping due to hypotension. No additional changes were made to the patient's therapy. A repeat assessment showed improved NYHA class (-1 class), improved 6-minute walk test (+83 m), a decrease in Doppler estimated systolic pulmonary pressure (-30 mmHg), and an increase in RV ejection fraction (+11%) and stroke volume (+15 ml). Discussion: PAH is a progressive disease, and current treatments of PAH have a minimal impact on the pulmonary artery pressure and RV ejection fraction or stroke volume, and are therefore considered to slow the progression of the disease rather than modifying its course. The current case shows an unexpected change in the natural history of the disease which appears to be associated with the introduction of copper chelating therapy. While ATN-224 was poorly tolerated at the dose used (systemic blood pressure drop), we suspect that the short duration of treatment with ATN-224 led to significant ""de-remodeling"" of the pulmonary vascular lesions, as seen in the experimental animal PAH model. The outcome of this single case, in our opinion, justifies the conduct of additional studies with copper chelation in PAH.",pulmonary hypertension;patient;human;therapy;American;society;chelation;heart ejection fraction;lung artery pressure;heart stroke volume;blood flow;dyspnea;cardiovascular magnetic resonance;fatigue;United States;echocardiography;lung vascular resistance;obstruction;lung lesion;case report;pathology;death;heart catheterization;female;experimental animal;blood pressure;hypotension;lung pressure;history;treatment duration;vascular lesion;model;experimental study;New York Heart Association class;Wilson disease;heart right ventricle failure;copper;choline tetrathiomolybdate;tetrathiomolybdic acid;chelating agent;sildenafil;bosentan;amlodipine,"Grinnan, D.;Abbate, A.;Farr, G.;Bogaard, H. J.;Voelkel, N. F.",2014,,,0,0,
1440,Penicillamine-induced elastosis perforans serpiginosa: Is useful switching to zinc?,"Objective: Elastosis perforans serpiginosa (EPS) is an infrequent, though not exceptional, penicillamine cutaneous adverse effect. Here is described a 15-year-old white boy with neurological and hepatic onset Wilson Disease (WD) who developed keratoticgranulomatous annular popular cutaneous lesions on the nuchal area and right arm during the 3rd year of penicillamine therapy. Methods: WD was diagnosed at the age of 12 years for the presence of irregular proximal tremulousness, dysarthria, micrographia, labile mood and inappropriate behavior. The patient showed also hepatomegaly and splenomegaly with mild hypertransaminasemia. Diagnosis was based on low ceruloplasmin serum levels, high 24-h urinary copper values, high liver copper concentration, and bilateral Kayser-Fleischer rings. Molecular analysis showed the presence of compound heterozygous mutation in the gene ATP7B. Therapy with penicillamine was started with a favourable response on neuropsychiatric symptoms. Liver function tests (LFTs) persisted normal. On the basis of lesions features and findings of skin biopsy EPS was diagnosed. Results: Topical steroid treatment were tried with no benefit. Since skin lesions worsened with a significant visual impact, penicillamine therapy was suspended after 3 months from the onset of EPS and replaced with zinc acetate. In the following months, cutaneous lesions persisted unchanged without histological signs of progression after three years of zinc monotherapy, while general clinical condition and LFTs remained normal. Conclusions: Although penicillamine is an effective and generally safe drug for patients with WD, the risk of some severe cutaneous and non cutaneous adverse events could suggest a more extensive use of zinc monotherapy as maintenance therapy in WD patients.",elastosis;human;patient;skin defect;therapy;monotherapy;hepatomegaly;mood;Wilson disease;tremor;risk;maintenance therapy;dysarthria;arm;boy;skin biopsy;liver function test;gene;liver;male;ceruloplasmin blood level;mutation;diagnosis;hypertransaminasemia;splenomegaly;adverse drug reaction;penicillamine;zinc;copper;zinc acetate;steroid,"Ranucci, G.;Di Dato, F.;Leone, F.;Tufano, M.;Vajro, P.;Spagnuolo, M. I.;Iorio, R.",2014,30 Sep,http://dx.doi.org/10.1016/j.dld.2014.07.113,0,0,
1441,To study cause of death in patients of neurological Wilson's disease,Objectives: To study cause of death in patients of neurological Wilson's disease. Background: Wilson's disease (WD) is a treatable autosomal recessive disorder of copper metabolism and is characterised by protean manifestations due to accumulation of copper in liver brain cornea and other tissues. Although treatable but still deaths in patients of WD are not rare. Methods: We studied cause of death in 44 patients who were diagnosed WD based on detailed clinical evaluation Kayser- Fleischer ring in cornea and biochemical studies (decreased serum ceruloplasmin and serum copper and increased urinary copper) and neuroimaging. Results: A total of 6 patients (13.6%)died during the observation period. The main cause of death was the delay in diagnosis. The mean delay in diagnosis for all patients was 18.9 months while it was 25.4 months for those who died. Of the 6 patients who died5 patients had dystonic presentation while one had parkinsonian presentation. Five of the 6 patients were juveniles (age below 18 years) and one was adult. Four of the 6 patients showed poor compliance for the treatment (zinc and penicillamine) as well as for the regular follow up. Conclusion: Early and correct diagnosis institution of proper treatment and lifelong continuation can prevent devastating consequences as WD is a treatable disorder.,patient;human;neurology;Indian;cause of death;Wilson disease;diagnosis;cornea;ceruloplasmin blood level;clinical evaluation;death;tissues;copper metabolism;adult;juvenile;follow up;brain;neuroimaging;diseases;copper blood level;liver;autosomal recessive disorder;copper;penicillamine;zinc,"Kumar, N.;Joshi, D.",2014,October,,0,0,
1442,"Wilson's disease: Ten years retrospective experience at national liver institute, Egypt","Background and aims Wilson's disease (WD) is a rare, inherited, genetic disorder of copper metabolism. Our aims to determine common clinical presentations, laboratory findings, diagnostic methods and long term outcome in Egyptian patients. Methods All medical records, between 2000 and 2010 in the paediatric hepatology department, were reviewed. Detailed follow-up data of the disease had been collected for each patient. Serum ceruloplasmin, liver function tests and other routine laboratory investigations. Slit lamp examination for Kayser Fleisher rings and 24-hour urine for copper before and after penicillamine challenge were done. Percutaneous liver biopsy also was performed in most patients. Results The most significant hepatic presentation was jaundice and Kayser Flisher rings. The most significant laboratory findings were, copper excretion after challenge with depencillamine (1546.57 +/- 99.55 mug/Dl) and decrease of mean ceruloplasmin concentration (13.8 +/- 2.38 mg/dl) below 20 ug/dl. There were significant increase of albumin and significant improvement of prothrombin time after treatment. Conclusion Kayser Flisher rings, urinary copper excretion and low serum ceruloplasmin were considered sufficient to establish the diagnosis of WD. Liver biopsy may be needed for confirmation of the diagnosis and to assess the extent and severity of the disease.",organization;Egypt;liver;human;laboratory;patient;ceruloplasmin blood level;liver biopsy;excretion;diagnosis;diagnostic procedure;medical record;follow up;slit lamp;urine;liver function test;copper metabolism;jaundice;prothrombin time;genetic disorder;copper;penicillamine;albumin;ceruloplasmin,"Salama, E.;Behairy, E.;Ahmed, A.;Nermin, M.;Ahmed, M.",2014,October,http://dx.doi.org/10.1136/archdischild-2014-307384.802,0,0,
1443,A phase I pharmacokinetic profiling study in patients receiving trientine dihydrochloride for the treatment of Wilson disease,"Background and aim: Trientine dihydrochloride (trientine) is a common treatment for Wilson disease, however data on pharmacokinetics are limited to healthy subjects. Aim of the study was to determine PK parameters assumed to be representative of steady state in Wilson disease patients treated with trientine. ClinicalTrials.gov Identifier: NCT01874028 Patients and methods: Twenty subjects (9 male, 4 children, mean age 39.3 y [12-61]) with confirmed diagnosis of Wilson disease were exposed to trientine after oral dosing at the standard dose for that subject. Blood samples were taken 0,5; 1; 1,5; 2; 3; 4; 6; 8 and 12 h after dosing. Concentration of trientine in plasma samples were measured by LC-MS/MS after protein precipitation extraction over the calibration range of 20-2000 ng/mL Results: Trientine was absorbed rapidly, with tmax occurring between 0.48 and 4.08 hours post dose. There was some variability in exposure, with a 10-fold range in Cmax, and a 13.8-fold range in AUC0-t. This variability was slightly lower when PK parameters were dose-normalised (6.7-fold range in Cmax/D and an 11.6-fold range in AUC0-t/D). The terminal half-life, where defined, was broadly consistent between subjects (range of 2.33-6.99 hours). The AUC0-8 was able to be calculated in 14 of the 20 subjects, however since the dosing occurred at pharmacokinetic steady state the AUC0-t is representative of exposure during the dosing interval. There was no marked difference in PK parameters between adult subjects (n=16) and children (n=4). The Cmax range was 508-3100 ng/mL in adults and 309-1940 ng/mL in children-the equivalent ranges for AUC0-t were 1240-17100 ng.h/mL and 1500 8060 ng.h/mL respectively. When PK parameters were normalised for dose given, the Cmax/D and AUC0-t/D for children were contained within the ranges for the adult subjects. Conclusion: The pharmacokinetics of trientine in Wilson disease subjects was similar to that reported in healthy subjects. (Figure presented).",patient;human;Wilson disease;liver disease;liver;pharmacokinetics;concentration (parameters);child;parameters;adult;exposure;normal human;maximum plasma concentration;steady state;extraction;precipitation;plasma;blood sampling;half life time;diagnosis;male;trientine;protein,"Weiss, K. H.;Teufel, U.;Pfeiffenberger, J.;Rupp, C.;Wannhoff, A.;Stremmel, W.;Gotthardt, D.",2014,October,http://dx.doi.org/10.1002/hep.27501,0,0,
1444,Sex differences in liver SAM:SAH ratios and gene transcript levels after pre-and post-natal choline supplementation and copper chelation treatment in an animal model of wilson disease,"Background. Methionine metabolism, central to DNA methylation reactions, may provide epigenetic regulation of genes involved in liver damage in Wilson disease (WD). We hypothesized that peri-natal maternal treatment with choline could modify the sex specific response to penicillamine in offspring in the tx-j model of WD. Methods. Control (choline 8 mmol/ Kg) or choline supplemented (36 mmol/Kg) diets were fed to wildtype and tx-j female mice starting at 2 weeks before mating and continuing in offspring up to 24 weeks of age. A subgroup of tx-j of both sexes received oral penicillamine with or without choline supplemented diet from 12 to 24 weeks of age. Results. Decreased S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio, an index of DNA methylation capacity was decreased in each sex of offspring tx-j mice, compatible with the known down-regulation of SAH hydrolase levels in this mouse model of WD (Table 1). The SAM:SAH ratio was higher in untreated female versus male tx-j mice (p<0.05). Separate choline or penicillamine treatments were associated with similar increases of SAM:SAH ratio in male tx-j vs wildtype levels. Whereas the ratio was increased by each separate treatment in tx-j males, it was reduced by each separate treatment in tx-j females, but was unchanged in either sex by the combination of choline and penicillamine. Transcript levels of Dnmt3b a regulator of DNA methylation in tx-j mice, were increased in untreated tx-j of either sex, and were down-regulated by separate or combined penicillamine and choline treatment in male tx-j, but were unchanged by any treatment in female tx-j mice. Grp78 transcript levels were increased in tx-j mice of both sexes, reduced to control levels by choline in tx-j males but only by combined penicillamine and choline treatment in female tx-j mice. Conclusions. Our results indicate different sex responses to copper chelation and methyl donors in the tx-j model of WD that could explain different phenotype between genders in WD. (Table presented).",liver;animal model;Wilson disease;chelation;supplementation;gene;liver disease;sex difference;mouse;male;female;progeny;DNA methylation;diet;model;liver injury;mouse model;mating;metabolism;maternal treatment;down regulation;gender;phenotype;donor;choline;copper;penicillamine;dna;hydrolase;s adenosylhomocysteine;s adenosylmethionine;methionine,"Medici, V.;Shibata, N.;Kharbanda, K. K.;Halsted, C. H.",2014,October,http://dx.doi.org/10.1002/hep.27501,0,0,
1445,No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson's disease during long term follow up,"Background and aims: Although liver cirrhosis is a frequent complication in Wilson's disease (WD), data on risk of hepatocellular carcinoma (HCC) in these patients are scarce. We here report HCC risk in a well-defined cohort with unequivocally proven WD with long-term follow-up (FU) and correlate HCC risk to efficacy of decoppering treatment and severity of liver disease. Methods: All patients with a confirmed diagnosis of WD (Leipzig score >= 4) in three Dutch university referral hospitals were included in this retrospective cohort study. End of FU was defined as date of diagnosis of HCC, liver transplantation death or last available hospital visit. Results: In total, 130 patients with WD were followed during a median FU of 15 years (range 0.1-51.2). Total years of FU was 2336. Median age at diagnosis was 16 years (range 0-43). Presentation was asymptomatic, exclusively hepatic, neurologic, combined and unknown in 4%, 55%, 9%, 30% and 2% of cases, respectively. Median Leipzig score was 8 points (range 4-13). At baseline cirrhosis was present in 74 patients (57% of total: 64% compensated and 36% decompensated). At end of FU, liver disease severity was improved, stable or deteriorated in 20% 46% and 24% of all cases, respectively. Twenty-eight patients received a liver transplant. Five patients died due to complications of their liver disease and two deaths were related to liver transplantation. In patients who were treated for at least one year (n=111), zinc, penicillamine or trientine (alone, sequentially or combined) were prescribed in 92%, 69% and 14% of patients, respectively. At the end of FU, efficacy of decoppering based on values of serum non-ceruloplasmin-bound copper concentration (aim: <10 mg/dL) and 24-hour-urinary copper excretion (aim: <100 mg/24 hours), was excellent in 34% of patients, moderate in 42%, poor in 13% and unknown in 11%. Two patients developed HCC. The first patient was a 39-year-old male and presented with decompensated cirrhosis in combination with HCC. The second patient was a 63-yearold female with unequivocal WD diagnosed 50 years earlier. Despite excellent decoppering at the end of FU, she progressed to decompensated cirrhosis in which an HCC developed. No additional risk factors for liver disease were present in both patients. Estimated annual HCC risk for all patients was 0.09% (95% confidence interval: 0.01-0.28). Subgroup analysis in cirrhotic patients revealed an annual HCC risk of 0.14% (95% confidence interval: 0.02-0.45). Conclusion: Even in case of cirrhosis, HCC risk is low in Wilson's disease and appears not related to efficiency of decoppering. Our data do not support regular HCC surveillance in WD.",risk;liver cell carcinoma;liver cirrhosis;follow up;liver disease;liver;Wilson disease;patient;human;diagnosis;liver transplantation;decompensated liver cirrhosis;confidence interval;hospital;death;cohort analysis;risk factor;excretion;serum;university;liver graft;disease severity;male;female;copper;ceruloplasmin;trientine;penicillamine;zinc,"Van Meer, S.;De Man, R. A.;Van Den Berg, A. P.;Houwen, R.;Linn, F.;Siersema, P. D.;Van Erpecum, K. J.",2014,October,http://dx.doi.org/10.1002/hep.27501,0,0,
1446,Neuropsychiatric interface in a patient with depression,"Psychiatric manifestations are significantly predominant in majority of the patients with Wilson's disease (WD) at the time of onset. Nearly half of the patients undergo psychiatric hospitalization before diagnosis of WD. Aims/ Objectives: To report a case of WD who presented with non responding depression. Methodology: A 31 years old patient came with complains of gradual onset of withdrawn behavior, irritability, sadness of mood, and slowness of movements since 1 year. A diagnosis of Major Depressive Disorder was made by a private psychiatrist. He was started on antidepressants and received 10 Electro Convulsive Therapy. However, he perceived no improvement and discontinued treatment due to side effects. Patient presented in KJSH after 6 months due to worsened symptoms. On enquiry, h/o tremulousness, slurring of speech and leaning of body backwards while sitting since few months. Neurological examination revealed brisk deep tendon reflexes. On MSE, patient had retarded psychomotor activity, grimacing facial movements with mannerisms. His mood was sad with restricted affect. Ideas of helplessness, hopelessness and death wishes were expressed. MRI showed gliosis with calcification in bilateral basal ganglia. On ophthalmological examination, Keyser Fleischer ring seen. Investigations revealed raised liver enzymes and high urine Cu. Patient was diagnosed with Wilson's disease and started on Tab. Penicillamine. Discussion: Although WD is rare, it commonly presents with psychiatric symptoms. Depression is extremely common in WD patients, affecting 30-60% of them. The mood disturbance show limited response to anti depressants, whereas, use of chelating agent leads to normalisation of mood and improvement in non-psychiatric symptoms. Conclusion: Psychiatrists has to be aware of psychiatric manifestations of WD. A differential of Wilson's disease can be considered if patient shows poor response or excessive sensitivity to the psychotropic medications. Consultation liaison across multiple specialties like neurology, ophthalmology is required for comprehensive management of WD.",human;Indian;medical society;patient;mood;diagnosis;mental disease;psychiatrist;Wilson disease;psychomotor activity;tendon reflex;sitting;speech;major depression;methodology;mood disorder;neurologic examination;consultation;gesture;urine;calcification;slowness;gliosis;death;basal ganglion;examination;tremor;hopelessness;side effect;drug therapy;helplessness;neurology;ophthalmology;irritability;hospitalization;convulsive therapy;nuclear magnetic resonance imaging;antidepressant agent;penicillamine;liver enzyme;chelating agent;psychotropic agent,"Dere, S. S.;Shah, B.;Jadhav, B.;Dhavale, H.",2014,January,,0,0,
1447,Wilson's disease: Catatonia as the only manifestation,"Introduction: Catatonia is a clinical presentation with varied causes ranging from infectious causes to metabolic causes. Wilson's disease is one of the known causes of catatonia, but catatonia has been reported as a rare presentation (0.01%) of Wilson's disease. We hereby report a case of Wilson's disease presenting as catatonia as the only manifestation. Case Report: Ms. S, a 20-year-old, young unmarried Muslim female presented with acute onset 5 month history suggestive of catatonia (mutism, stupor, ambitnedency, waxy flexibility, and rigidity). Patient had no past history of psychiatric illness. Family history of suicide in an elder brother and two elder sisters having died of 7 months illness of similar presentation was there. Patient did not respond to intravenous lorazepam trial of 3 days and 10 modified electroconvulsive therapy. Magnetic resonance imaging (MRI) brain revealed multiple hyperintensities in internal capsule and basal ganglia. Ultrasonography (USG) abdomen was normal. Biochemical investigations showed increased urinary copper, decreased serum copper, and decreased blood ceruloplasmin. Slit lamp examination was unremarkable and neuropsychiatric examination revealed a catatonic state with no obvious cardinal neurological manifestations of Wilson's disease. Diagnosis of Wilson's disease was made and patient improved on penicillamine, zinc sulfate, and lorazepam. Implications: Wilson's disease should be kept as a differential diagnosis in young adults presenting with catatonia.",medical society;catatonia;Indian;Wilson disease;human;patient;mental disease;nuclear magnetic resonance imaging;mutism;rigidity;electroconvulsive therapy;female;diagnosis;brain;capsula interna;slit lamp;stupor;blood;diseases;copper blood level;suicide;examination;abdomen;differential diagnosis;young adult;echography;basal ganglion;family history;Moslem;case report;lorazepam;penicillamine;ceruloplasmin;copper;zinc sulfate,"Singh, A. P.;Kukreti, A. K. P.;Jhirwal, O.",2014,January,,0,0,
1448,Metal chelating pseudopeptides and their potential medical applications,"Wilson's disease (WD) is one of the major genetic disorders of copper (Cu) metabolism in human. In this rare disease the ATPase ATP7B in charge of the excretion of excess Cu from the liver cells is defective and consequently, toxic Cu accumulates in the liver [1]. To treat WD, we propose innovative Cu chelators, with the following properties: (i) they show a high affinity for Cu(I), which is the oxidation state of excess intracellular Cu (ii) they are selective for Cu(I) with respect to potentially competing endogeneous metals such as Zn(II) and (iii) they are water soluble. Mimics of binding sites found in proteins involved in Cu homeostasis are good candidates that meet all these expectations. Therefore, pseudopeptides were designed to mimic Cu(I) coordination by metal-sequestering proteins such as metallothioneins. They are built from nitrilotriacetic acid (NTA) as a tripodal anchor and functionalized with three amino acids cysteine or D-Penicillamine [2, 3]. The C<inf>3</inf>-symmetric nonbiological scaffold acts as a platform that orients the three binding arms in the same direction to coordinate the Cu(I) ion. To promote intracellular Cu chelation and internalization in hepatocytes, these sulphur ligands have been functionalized with sugar units to target liver cells via the asialoglycoprotein receptors (ASGP-R). The obtained glycoconjugates were demonstrated to release high affinity Cu chelating agents in the hepatic cells. This confirms that the use of intracellular Cu(I) chelators is very promising to treat Cu overload in WD [4]. (Figure presented) .",inorganic chemistry;liver cell;imaging software;human;rare disease;liver;homeostasis;internalization;chelation;genetic disorder;cardiac resynchronization therapy device;binding site;arm;excretion;oxidation;Wilson disease;copper metabolism;metal;chelating agent;cuprous ion;protein;nitrilotriacetic acid;sugar;sulfur;asialoglycoprotein receptor;amino acid;cysteine;water;penicillamine;zinc;ligand;adenosine triphosphatase;glycoconjugate;cupric ion;copper ion,"Jullien, A. S.;Monestier, M.;Pujol, A.;Lebrun, C.;Gateau, C.;Charbonnier, P.;Cuillel, M.;Mintz, E.;Delangle, P.",2014,August,http://dx.doi.org/10.1007/s00775-014-1157-y,0,0,
1449,Possible implications of copper chelation on iron homeostasis in Wilson disease patients. Penicillamine effect on ceruloplasmin ferroxidase activity,"Introduction: Ceruloplasmin (Cp) belongs to multi-copper ferroxidase family of proteins. It is involved in Fe loading into serum transferrin. Defective copper loading into apo-ceruloplasmin (apo-Cp) may result from mutations in the ATP7B gene characterizing Wilson disease (WD). Patients with WD are treated with copper chelators such as penicillamine (PA) Goals & Methods: We postulate that Cu- chelators will reduce copper incorporation into apo-Cp which will affect ferroxidase activity; consequently disturb iron homeostasis. We hereby investigate the in vitro effect of Cu, & Cu-PA on HepG2 viability (MTT assay), ferroxidase activity of Cp (pPD oxidase assay) and expression of Cp, ferritin and transferrin (Western blotting). In addition we examine the activity of serum Cp ferroxidase activity in 5 WD patients who are homozygous for a mutation in WND gene & are treated by PA. Results & conclusions: In vitro: Cu decreased (50%) viability of HepG2 cells while cotreatment with Cu-PA altered cell morphology significantly, decreased further cell viability (70%) and induced cell cycle arrest at G2/M phase. Cp expression in HepG2 cells increased with Cu, decreased with PA, & did not vary with Cu-PA. Ferritin expression in HepG2 cells decreased with Cu, PA and Cu-PA treated cells Transferrin expression show qualitative decrease in PA and Cu-PA treated cells In Vivo: All patients had very low serum Cp ferroxidase activity (0.007-0.01 units) compared to a control (0.022-0.027 units). Mild elevation was noted in 2 patients while transferrin level was in normal range. Cp Ferroxidase activity in both HepG2 cells and Serum of WD patients was significantly decreased. The recommended life treatment with Cu chelators would influence Fe incorporation into transferrin that may consequently lead to Fe deposition in liver. The implication of our findings necessitate the re-evaluation of PA treated WD patients for iron complications.",Ferroxidase;Penicillamine;Wilson disease;human;patient;homeostasis;chelation;serum;in vitro study;gene;mutation;MTT assay;liver;transferrin blood level;cell viability;cell structure;Western blotting;assay;cell cycle arrest;ceruloplasmin;iron;copper;transferrin;chelating agent;ferritin;protein;oxidoreductase,"Usta, J.;Majarian, T.;El-Rifai, O.;Barada, K.",2014,September,http://dx.doi.org/10.1111/febs.12919,0,0,
1450,Symptomatic copper deficiency in Wilson's disease patient treated with zinc sulphate,"Introduction: Wilson's disease (WD) is caused by excess of copper that leads to copper accumulation and needs life-long decoppering treatment. However, overtreatment with anti-copper agents may cause copper deficiency which may present with neurologic and hematologic symptoms. We report WD patient with copper deficiency during zinc sulphate therapy. Case report: A 37-year- old woman with presymptomatic WD diagnosed in 1998, treated with zinc sulphate was admitted to our clinic in 2013 because of paraesthesias in the fingers and toes for 3 months. Her neurological examination was normal. She had leucopenia (WBC 2.9 x 10<sup>9</sup>L, normal range 4.5-10.5 x 10<sup>9</sup>/L). Serum ceruloplasmin 0.92 mg/dl (normal range 25-45), copper serum concentration< 5 lg/dl (normal range 70-140), urinary copper excretion 11 lg/24 h (normal range 0-50) were markedly decreased. MRI of cervical spine showed linear increased T2 signal lesion in the posterior column of the cervical cord. Somatosensory evoked potentials showed impaired conduction in the dorsal column. Electromyography didn't show neuropathy. Vitamin B12 level was in normal range. Liver function tests were normal. Zinc sulphate was withdrawn. Within 1 month leucopenia resolved completely. Serum ceruloplasmin (5 mg/ dl) and serum copper concentration (20 lg/dl) 6 months later were higher than in previous tests. Urinary copper excretion was still low (12.5 lg/24 h). MRI of cervical spine 6 month later demonstrate marked improvement. Nine months after interruption in anti-copper treatment, d-penicillamine instead of zinc sulphate was introduced. Conclusion: Copper deficiency as result of anti-copper treatment may cause neurological and hematological signs. Treatment must be regularly monitored.",patient;human;neurology;copper deficiency;Wilson disease;excretion;ceruloplasmin blood level;copper blood level;leukopenia;cervical spine;evoked somatosensory response;leukocyte;cervical spinal cord;neurologic examination;nuclear magnetic resonance imaging;toe;liver function test;blood level;hospital;neuropathy;electromyography;spine;case report;therapy;female;zinc sulfate;copper;penicillamine;cyanocobalamin;vitamin,"Dziezyc, K.;Sobanska, A.;Litwin, T.;Chabik, G.;Czlonkowska, A.",2014,May,http://dx.doi.org/10.1007/s00415-014-7337-4,0,0,
1451,Neuro-Wilson disease: About seven cases and review of the literature,"Introduction: Wilson disease is an autosomal recessive disorder of copper overlap, dominated by neuropsychiatric and hepatic symptoms. The aims is to to review the genetic aspects, diagnosis and treatment of Neuro-Wilson through a series of patient followed in the neurology department sahloul, CHU Sousse. Methods: We report seven cases collected in the department of neurology CHU Sahloul Sousse. All patients had neurological signs with or without extraneurological symptoms. The diagnosis of Wilson's disease was based on clinical, biological and radiological result. Results: Seven patient, two boys and five girls. The mean of age was 25.5 with an extreme ranging from 14 to 48 years. The neurological signs were reviling the disease in six patients and the most common symptoms were tremor. One patient had cerebellor ataxia and another has had seizure. Three of patients had a familial form with an autosomal recessive transmission. The ring of kayser flecher was found in one patient. Cupric balance was disturbed in all patients including one associated hemochromatosis. The cerebral MRI was pathologic in two patients with lesions in basal ganglia. All patients was treated by D penicillamine with good evolution in five patients. Conclusions: When left untreated, the evolution of Wilson's disease is always fatal. Treatment is based on the chelating copper, zinc salts and liver transplantation.The prognosis of Wilson's disease appears even better than the neurological and liver symptoms are not pronounced.",Wilson disease;neurology;human;patient;liver;neurologic disease;diagnosis;basal ganglion;autosomal recessive inheritance;male;female;hemochromatosis;seizure;girl;autosomal recessive disorder;tremor;prognosis;boy;nuclear magnetic resonance imaging;copper;penicillamine;zinc derivative,"Ben Algia, L.;Chatti, I.;Benhalima, M.;Saied, Z.;Khefifi, A.;Ben Amor, S.;Benammou, S.",2014,May,http://dx.doi.org/10.1007/s00415-014-7337-4,0,0,
1452,Mixed-type polyneuropathy in Wilson's disease,"Introduction: Wilson'sDisease (WD)is an autosomal recessive disorderof abnormal copper metabolism witch predominantly affects the central nervous system and the liver. Peripheral nervous system involvement is rarely reported in the context of WD and not well characterized. Objectives: To report a WD patient with peripheral neuropathy. Design: Case report. Setting: Neurology Diagnostic Unit, P.O.San Martino, Oristano, Italy Methods: A 58-year-old male suffering from WD on therapy with trientine referred to our center because of mild distal limb weakness with hypoesthesia. Clinical evaluation showed mild leg weakness with foot drop and hyporreflexia. A nerve conduction study was performed using standard techniques (Medtronic Keypoint v5.09). Distal motor latency, Fwave latency, motor nerve conduction velocity and CMAP were evaluated in the deep peroneal, posterior tibial, median and ulnar nerves; sensory nerve conduction velocity and SAP were measured in the sural, superficial peroneal, median, ulnar and radial nerve. Analysing his anamnestic and laboratoristic data no other cause of polyneuropathy was found. Results: Electroneurographyc findings suggested an asymmetric lengthdependent sensory-motor neuropathy of mixed type. Conclusion: We confirmed peripheral nervous system involvement in WD. According to the literature, also our findings showed both myelin and axonal damage. Polyneuropathy may appear despite therapy, although a iatrogenic contribution cannot be excluded.",polyneuropathy;electroneurology;Wilson disease;peripheral nervous system;human;therapy;latent period;peroneus nerve paralysis;autosomal recessive inheritance;peripheral neuropathy;limb weakness;clinical evaluation;case report;neurology;patient;central nervous system;motor nerve conduction;sensory nerve conduction;hypesthesia;motor neuropathy;leg;weakness;liver;nerve conduction;Italy;diagnosis;ulnar nerve;male;radial nerve;copper metabolism;trientine;myelin,"Aste, R.;Salaris, E.;Pische, M. G.;Floris, E. R.",2014,June,,0,0,
1453,A novel pathogenic ATP7B mutation in a Thai patient with very mild form of Wilson's disease,"Objective: To described a novel mutation of Wilson's disease and its clinical manifestations. Background: Wilson's disease(WD) is an autosomal recessive disorder of copper metabolism arising from the mutation of ATP7B gene, located on chromosome 13. The H1069Q mutation which is the most frequent mutation in the United State and northern Europe, associated with the late onset and less severity. Methods: A 39 year old female, master's degree graduated. She presented with progressive right hand dystonia and noticed mild weakness on right hand for 25 years. Three years after onset it progressed to generalized dystonia and chorea. She didn't have tremor, rigidity, or seizure. She had no history of psychiatric problem and no other underlying disease. There was no family history of WD. She was diagnosed with WD from other hospital but she lost follow up for 5 years. Physical examination showed no sign of chronic liver stigmata. She had generalized dystonia which was more prominent on right hand and orobuccolingual region and generalized chorea which was more prominent on the left side. She had mild weakness on left side and normal eye movement. Eye examination showed Kayser-Fleischer ring. She had no rigidity and tremor, had normal cerebellar sign, normal sensation and no other long tract sign. The investigations showed low level of serum ceruloplasmin,2 mg/dl(20- 60), normal serum copper,0.33 ppm(0.66-1.50) and high level of urine copper,98 ug/24hr-ur(17-43). Liver function test and synthetic function of liver were in normal range. MRI brain showed typical characteristic of WD.Mutation screening in all 21 exons of ATP7B gene was performed using denaturing high-performance liquid chromatography followed by sequencing of the altered fragments. Results: A novel single-base deletion resulting in a novel frameshift translation, NM-000053.2(ATP7B) c.3168delT;p.Leu1057 Trpfs*64 and a splicing defect in intron 17,NM-000053.2(ATP7B) c.3700-1G>C (IVS17-1G>C) were identified in this patient. She was treated with D-penicillamine and zinc sulfate. Clinical improved. KF ring disappeared. Serum ceruloplasmin and urine copper level returned to normal range. Conclusions: The patient presented with progressive generalized dystonia chorea without other typical sign and symptom of WD. The disease severity was mild. The genetic test showed a novel mutation of WD. This mutation may be associated with a favorable prognosis. (Figure Presented).",patient;mutation;human;motor dysfunction;Parkinson disease;Wilson disease;generalized dystonia;chorea;gene;urine;rigidity;weakness;tremor;liver;ceruloplasmin blood level;eye movement;physical examination;copper metabolism;disease severity;prognosis;follow up;dystonia;splicing defect;Europe;autosomal recessive disorder;hospital;screening;family history;United States;brain;exon;denaturing high performance liquid chromatography;liver function test;intron;seizure;chromosome 13;copper blood level;sensation;female;eye examination;nuclear magnetic resonance imaging;copper;penicillamine;zinc sulfate,"Sringean, J.;Amornvit, J.;Limwongse, C.;Bhidayasiri, R.",2014,May,http://dx.doi.org/10.1002/mds.25914,0,0,
1454,To study the response of treatment in patients of neurological Wilson's disease,"Objective: To evaluate the response of treatment in patients of neurological Wilson's disease. Background: Wilson's disease (WD) is an autosomal recessive disease caused by mutations in the ATP7B gene which makes a protein important for copper transport and elimination of excess copper . from the body. The disease presents with features that mainly suggest involvement of the liver and the brain. It most commonly affects children or young adults and runs an invariably fatal course if not adequately treated by decoppering therapy. Zinc and Dpenicillamine are the commonly available drugs for treatment of WD in India. Methods: This study was carried on 31 patients who were diagnosed as WD based on clinical features suggestive of WD; detection of Kayser-Fleischer ring in cornea by slit lamp examination and biochemical parameters (24-hour urinary copper more than 100 micrograms/ day; serum ceruloplasmin below 20 mg/dl and serum copper below 75 micrograms/dl). All the patients were given zinc and penicillamine. Results: All the 31 patients were started on zinc (elemental zinc 50 2150mg/day) and copper chelation therapy with penicillamine (250-1500 mg/day). Neurological worsening occurred in 16 (51.6%), decreased platelets in 13 (54.2%), increased transaminases in 6 (19.4%) and skin rashes in 5 (16.1%) patients. In these patients, penicillamine was withdrawn and was restarted after stabilisation of the clinical and biochemical parameters. Adjunctive therapy with trihexyphenidyl, levodopa and pyridoxine was used. After reinstituting penicillamine, 10 (32.25%) patients showed improvement. Of the remaining 6 (19.4%) patients, 4 (12.9%) never recovered to their pre-penicillamine status and were lost in follow-up. The remaining 2 (6.45%) patients deteriorated further and died. 24- hour urinary copper measurement was done in patients for monitoring the adequacy of treatment. Variable improvements were noted - 13 (41.9%) improved completely to pre-disease level of functioning; 12 (38.7%) showed incomplete improvement with sequelae; 4 (12.9%) were lost in follow up and 2(6.45%) patients died. Conclusions: Twenty five (80.6%) of our patients showed improvement with more than half of them showing complete improvement. Thus early and correct diagnosis along with institution of proper treatment (with careful clinical and biochemical monitoring) and lifelong continuation can prevent devastating consequences as the disease is treatable.",human;motor dysfunction;patient;Parkinson disease;Wilson disease;monitoring;parameters;follow up;therapy;chelation therapy;gene;autosomal recessive disorder;thrombocyte;young adult;diagnosis;child;copper blood level;ceruloplasmin blood level;brain;slit lamp;liver;rash;cornea;clinical feature;India;mutation;penicillamine;copper;zinc;protein;levodopa;pyridoxine;trihexyphenidyl;aminotransferase,"Kumar, N.;Joshi, D.",2014,May,http://dx.doi.org/10.1002/mds.25914,0,0,
1455,A case of copper deficiency myelopathy with features of Parkinsonism and brain iron accumulation,"Objective: To present a case of copper deficiency myelopathy with features of Parkinsonism and brain iron accumulation. Background: Copper deficiency myelopathy (CDM) occurs as a result of acquired copper deficiency and is similar in appearance to subacute combined degeneration of vitamin B12 deficiency. Acquired copper deficiency is rare and can occur as a result of gastric surgery, excessive zinc ingestion, prolonged TPN and malabsorption. Progressive spastic tetraparesis, paresthesias and sensory ataxic gait are seen in CDM. Characteristic MRI findings are hyperintensities in the dorsal columns of the cervical spine with extension into the brainstem. Hypointensities on brain MRI have not been reported. We report a case of CDM with features of Parkinsonism and brain iron accumulation. Results: An 81 year old male presented with a 20 year history of progressive gait instability, leg rigidity and macrocytic anemia. He was diagnosed and treated for vitamin B12 deficiency. Serum ceruloplasmin (CP), copper (Cu) and urine Cu excretion levels were consistently low at 10.3 mg/dL, 0.48 mcg/mL and 9 ug/spec. The patient denied a history of gastric surgery or excessive zinc supplementation. He was treated with oral and IV Cu without response. Five years from presentation he was found to have Parkinsonism including; bradykinesia, rigidity, masked facies, hypophonia and sialorrhea. He had markedly stooped posture and spastic gait. A trial of Levodopa was unsuccessful. MRI brain revealed iron deposition consistent with aceruloplasminemia (ACP). Iron, transferrin, ferritin, zinc and HgbA1c were normal. CP gene testing did not show previously identified mutations consistent with ACP. Conclusions: This case is unique in two ways: no underlying cause for the Cu deficiency without correction of serum levels after treatment and brain iron accumulation found on MRI suggestive of neurodegeneration with brain iron accumulation (NBIA). MRI findings and low urinary Cu excretion excludes Wilson's disease (WD). This case appears to be one of a subgroup of patients with low CP and Cu levels who do not fit into either diagnosis of WD or ACP. This combination of CDM and NBIA has not been described and could either represent a novel form of ACP or two co-existing diseases in a single individual. Brain MRI should be obtained in cases of CDM, especially in those with progressive symptoms or lack of response to Cu supplementation.",brain;copper deficiency;spinal cord disease;motor dysfunction;parkinsonism;Parkinson disease;nuclear magnetic resonance imaging;stomach surgery;excretion;patient;human;rigidity;supplementation;malabsorption;cervical spine;spine;brain stem;male;gait;body posture;ataxic gait;ingestion;subacute combined degeneration;bradykinesia;paresthesia;urine;quadriplegia;macrocytic anemia;facies;hypersalivation;spasticity;spastic gait;diseases;gene;mutation;laryngeal mask;diagnosis;neurodegeneration with brain iron accumulation;leg;blood level;ceruloplasmin blood level;Wilson disease;iron;zinc;cyanocobalamin;vitamin;levodopa;transferrin;copper;ferritin,"Frei, K. P.;Fuentes, J.;Dashtipour, K.;Tong, K.;Hunter, M.;Hamann, C.;Tsao, B.",2014,May,http://dx.doi.org/10.1002/mds.25914,0,0,
1456,Symptomatic copper deficiency in a Wilson's disease patient treated with zinc sulphate,"Introduction: Wilson's disease (WD) is caused by excess of copper that leads to copper accumulation and needs lifelong decoppering treatment. However, overtreatment with anti-copper agents may cause copper deficiency which may present with neurologic and hematologic symptoms. We report WD patient with copper deficiency during zinc sulphate therapy. Case report: A 37-year- old woman with presymptomatic WD diagnosed in 1998, treated with zinc sulphate was admitted to our clinic in 2013 because of paraesthesias in the fingers and toes for 3 months. Her neurological examination was normal. She had leucopenia (WBC 2.9x10<sup>9</sup> /L, normal range 4.5-10.5x10-9 /L). Serum ceruloplasmin 0.92 mg/dl (normal range 25-45), copper serum concentration <5?mu; g/dl (normal range 70-140), urinary copper excretion 11?mu; g/24h (normal range 0-50) were markedly decreased. MRI of cervical spine showed linear increased T2 signal lesion in the posterior column of the cervical cord. Somatosensory evoked potentials showed impaired conduction in the dorsal column. Electromyography didn't show neuropathy. Vitamin B12 level was in normal range. Liver function tests were normal. Zinc sulphate was withdrawn. Within 1 month leucopenia resolved completely. Serum ceruloplasmin (5mg/dl) and serum copper concentration (20?mu; g/dl) 6 months later were higher than in previous tests. Urinary copper excretion was still low (12.5?mu; g/24h). MRI of cervical spine 6 month later demonstrate marked improvement. Nine months after interruption in anti-copper treatment, d-penicillamine instead of zinc sulphate was introduced. Conclusion: Copper deficiency as result of anti-copper treatment may cause neurological and hematological signs. Treatment must be regularly monitored.",patient;human;neurology;copper deficiency;Wilson disease;excretion;ceruloplasmin blood level;copper blood level;leukopenia;cervical spine;evoked somatosensory response;leukocyte;cervical spinal cord;neurologic examination;nuclear magnetic resonance imaging;toe;liver function test;blood level;hospital;neuropathy;electromyography;spine;case report;therapy;female;zinc sulfate;copper;penicillamine;cyanocobalamin;vitamin,"Dziezyc, K.;Sobanska, A.;Litwin, T.;Chabik, G.;Czlonkowska, A.",2014,May,,0,0,
1457,Neuro-Wilson's disease - about seven cases and review of the literature,"Introduction: Wilson's disease is an autosomal recessive disorder of copper overlap, dominated by neuropsychiatric and hepatic symptoms. the aims is to to review the genetic aspects, diagnosis and treatment of Neuro-Wilson through a series of patient followed in the neurology department sahloul, CHU Sousse. Methods: We report seven cases collected in the department of neurology CHU Sahloul Sousse. All patients had neurological signs with or without extraneurological symptoms. The diagnosis of Wilson's disease was based on clinical, biological and radiological result. Results: Seven patient, two boys and five girls. The mean of age was 25.5 with an extreme ranging from 14 years to 48 years. The neurological signs were revealing the disease in six patients and the most common symptoms were tremor. One patient had cerebellor ataxia and another has had seizure. Three of patients had a familial form with an autosomal recessive transmission. The ring of Kayser Flecher was found in one patient. Cupric balance was disturbed in all patients including one associated hemochromatosis. The cerebral MRI was pathologic in two patients with lesions in basal ganglia. All patients were treated by D penicillamine with good evolution in five patients. Conclusions: When left untreated, the evolution of Wilson's disease is always fatal. Treatment is based on the chelating copper, zinc salts and liver transplantation .The prognosis of Wilson's disease appears even better than the neurological and liver symptoms are not pronounced.",neurology;Wilson disease;human;patient;neurologic disease;diagnosis;tremor;girl;male;boy;female;liver transplantation;prognosis;autosomal recessive disorder;basal ganglion;hemochromatosis;autosomal recessive inheritance;liver;seizure;nuclear magnetic resonance imaging;copper;penicillamine;zinc derivative,"Algia, L. B.;Chatti, I.;Benhalima, M.;Saied, Z.;Khefifi, A.;Amor, S. B.;Benammou, S.",2014,May,,0,0,
1458,Pregnancy in women with wilson's disease: The copper connect,"Background Wilson's disease is a rare autosomal recessive disorder of copper metabolism characterised by liver cirrhosis and neurological disorders. This is a report of two patients with Wilson's disease and their successful journey through pregnancy and lactation. There are only a few reports regarding the outcome of pregnancy in Wilson's disease (WD) from India. The authors in this study emphasise that pregnancy in Wilson's disease is safe and successful when treatment with a chelating agent is continued uninterruptedly. Case Case one was a 30 year old G4P1L1A2 known case of Wilson disease since 7 years of age. She had two miscarriages and one caesarean section in the past. She had been on d-penicillamine since 7 years of age which was changed to zinc sulphate as advised by neurophysician during pregnancy. She delivered by elective caesarean section and continued zinc sulphate postnatally. Case two was a 24-year-old G2A1 who was diagnosed to have Wilson's disease at 13 years of age. She had been on d-penicillamine and continued the same during pregnancy. She had discontinued penicillamine therapy on her own 1 year before her pregnancy and had developed severe psychotic symptoms, mood disturbances and poor memory. She was restarted on d-penicillamine with rapid improvement of symptoms. She had a healthy baby by normal vaginal delivery. Conclusion Successful pregnancies and uneventful full-term delivery may occur in mothers of WD on treatment.These women require anti copper therapy during their pregnancy. The major goal of treatment is to protect the mother from copper toxicity while protecting the fetus from possible teratogenesis due to low copper levels. A regimen of d-penicillamine during pregnancy can control the disease without harming the fetus. Treatment should not be stopped during pregnancy and zinc therapy should be considered. Patients with Wilson's disease contemplating pregnancy should have their hepatic function and copper status assessed.",human;female;pregnancy;Wilson disease;therapy;cesarean section;patient;mother;fetus;India;lactation;vascular guide wire;copper metabolism;spontaneous abortion;teratogenesis;toxicity;vaginal delivery;baby;memory;mood disorder;psychosis;neurologic disease;liver cirrhosis;liver function;autosomal recessive disorder;copper;penicillamine;zinc sulfate;zinc;chelating agent,"Mehta, P.;Vishwanath, U.;Agarwal, P.",2014,April,http://dx.doi.org/10.1111/1471-0528.12788,0,0,
1459,Complete neurological recovery in wilson disease: Experience with 100 consecutive patients seen from 2005-2013,"OBJECTIVE: Tostudy the neurological outcomes of Wilson disease (WD) following decoppering.BACKGROUND: Judicious decoppering can prevent WD related mortality and reverse neurological disability. DESIGN/METHODS: From 2005-2013 we prospectively recruited 100 consecutive patients with WD and WD related neurological disability. All received, penicillamine or trientine in recommmended doses (125 mg/day - up to 2 gm/day), in the initial decoppering phase of treatment. Treatment was tracked by using the standard WD specific scale, the Global Assessment Scale of Wilson Disease (GAS for WD).RESULTS: There was no mortality over the eight year study period. Of the 100 patients, 56 were men. The mean age at disease onset was 12.4 years (range 3-35). As per the three point disease severity scale (SS3), on recruitment, 43 % patients had severe neurological disability (defined as being bedbound, mute, requiring enteral feeding & bladder catheterization). While 37% had moderate and, 20% had mild neurological disability. Dystonia was the most frequent movement disorder (77%) followedby parkinsonism (53%) and tremor (47%). Of the 100 patients, 4 were lost to follow up after the initial visit and two were refractory to decoppering. All of the other 94 patients showed significant neurological recovery over a mean follow up of 20.7 months (range 4-36). Seventy per cent of the 94 patients (including 68% of patients with severe neurologic disability) showed complete neurological recovery and could resume normal lives at par with their peers. At last follow up, 30 % of the 94 patients exhibit on-going recovery. Promisingly, improvements were also seen in various movements disorders including dystonia and parkinsonism. Adverse events observed included, transient decoppering induced neurological deterioration (n=15), thrombocytopenia (n=20), emergent psychosis (n=10), skin rash (n=6), non-traumatic fracture (n=4), and penicillamine induced lupus (n=2). CONCLUSIONS: Our report reinforces that remarkable neurological recovery can be expected in patients with WD with judicious decoppering. Objective clinical assessments help in monitoring treatment and tracking resolution of disability.",Wilson disease;patient;human;neurology;disability;follow up;mortality;parkinsonism;dystonia;enteric feeding;fracture;monitoring;immobility;thrombocytopenia;disease severity;deterioration;diseases;gas;implanted spinal cord stimulator;tremor;motor dysfunction;bladder catheterization;psychosis;rash;clinical assessment;male;penicillamine;trientine;nitrogen 15,"Aggarwal, A.;Bhatt, M.",2014,,,0,1,
1460,Therapeutic efficacy of D-penicillamine encapsulated alginate nanoparticles in wistar rat model for non-wilsonian brain copper toxicosis,"Objectives: The aim of this study was to assess the therapeutic efficacy of orally administered D-penicillamine loaded nanoparticles (7.2 mg D-penicillamine/200 g body weight/day) to that of conventional D-penicillamine (14.4 mg D-penicillamine/200 g body weight/day) for 90 days in Wistar rat model for non-Wilsonian brain copper toxicosis.Background: D-penicillamine is unable to mitigate the brain copper overload and neurological manifestations in Wilson's disease patients.Methods: High performance liquid chromatography, atomic absorption spectrophotometry, biochemical estimations, neurobehavioral and histopathological studies, and nanoparticles preparation and their physicochemical characterization were carried out.Results: D-penicillamine nanoparticles exhibited mean 274.09 nm size coupled with less than 29.32% of D penicillamine release during 2 h under in vitro conditions. Pharmacokinetics studies showed augmented levels of D-penicillamine in brain of nanoparticles based D-penicillamine delivery group compared to conventional D-penicillamine delivery group. Conventional and nanoparticles based D-penicillamine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary copper levels, and acetylcholinesterase activity in rat model of copper toxicosis. Conventional D-penicillamine therapy resulted in negative rhodanine staining of liver and brain sections corroborated by 60.1%, and16.4% reduction in hepatic and brain copper content, respectively compared to non-treated copper-intoxicated group. However, liver and brain sections of nanoparticles based D-penicillamine therapy group demonstrated grade 1 copper and no copper depositions substantiated by 47.2% and 32.8% reduction in hepatic and brain copper content, respectively in comparison to non-treated copper-intoxicated group.Conclusions: Taken together, the present study reveals the first in vivo evidence for therapeutic efficacy of nanoparticles based D-penicillamine therapy in chelating more brain copper and alleviating neurological deficits even at half the dose as given in conventional D-penicillamine therapy.",Wistar rat;rat;rat model;brain;intoxication;neurology;therapy;liver;pharmacokinetics;in vitro study;histopathology;atomic absorption spectrometry;high performance liquid chromatography;memory;implantable cardiac monitor;staining;Wilson disease;penicillamine;alginic acid;nanoparticle;copper;rhodanine;acetylcholinesterase,"Pal, A.;Prasad, R.;Vasishta, R.;Thapa, B.",2014,,,0,0,
1461,"The course of pregnancy in wilson's disease-one center, 20 years' experience","Introduction: Under treatment or not, the course of pregnancy in patients with Wilson's disease and drug safety in lactation are issues not well understood. Materyal and Methods : In this study, 194 patients (156 index cases) in Istanbul Faculty of Medicine with a follow-up of median 51 months (13-105 months) and 1069 patient-years were evaluated retrospectively for pregnancy. All patients met EASL 2012 Wilson's disease guideline's criteria. Results: 20 (16 index cases) out of 84 women had a total of 49 pregnancies. On presentation, 7 patients had decompensated cirrhosis, 4 had compensated cirrhosis, 6 had neurological signs (dysarthria, tremor etc.) and 9 were in precirrhotic stage. Out of 16 pre diagnosis pregnancies, 9 resulted in spontaneous abortion. Out of 33 post diagnosis pregnancies, 5 resulted in spontaneous abortion and 5 underwent termination (one due to fetal anomaly and 4 on patients' request). Out of 23 live births, one was born premature and died in three weeks. No anomalies were reported in the other 22 and they are still alive and healthy. One patient was diagnosed with antiphospholipid syndrome and Wilson's disease after 7 abortions. Under treatment, she had a live birth following two miscarriages. One of the patients who discontinued her medication during pregnancy died in the second month postpartum due to liver failure. The other patient developed tremor in the third trimester and her treatment was started again. Drug doses were reduced during pregnancy; one patient was treated with zinc (100mg/d), one was treated with 600 mg of trientine plus 100 mg of zinc and others were treated with D-penicillamine 600 mg/d and zinc 100 mg/ d. Copper deficiency did not develop in any of the pregnancies. The patients breastfed their babies. After lactation, drug doses were increased when needed. No wound healing problems occurred after the c-section of 10 patients who were under D-penicillamine (600 mg/d) treatment. Conclusion : Wilson's patients can get pregnant under combination therapy (chelator and zinc) even if they present with decompansated cirrhosis. During pregnancy, drugs should be administered twice daily (D-penicillamine 600 mg/d, trientine 600 mg/d, zinc 100 mg/d) and treatments should never be discontinued. At given doses, D-penicillamine does not impair wound healing after c-section. No complications occurred when treatment was continued during lactation as long as the mother was thoroughly informed, but further studies are needed to better understand the subject.",pregnancy;gastrointestinal disease;Wilson disease;female;human;patient;lactation;spontaneous abortion;drug dose;diagnosis;wound healing;live birth;tremor;liver cirrhosis;third trimester pregnancy;decompensated liver cirrhosis;liver failure;follow up;drug therapy;abortion;mother;therapy;antiphospholipid syndrome;drug safety;fetus malformation;baby;copper deficiency;dysarthria;neurologic disease;Turkey (republic);zinc;penicillamine;trientine;chelating agent,"Demir, K.;Soyer, O. M.;Karaca, C.;Besisik, F.;Kaymakoglu, S.",2014,May,http://dx.doi.org/10.1016/S0016-5085%2814%2963671-4,0,1,
1462,Therapeutic chelation efficacy of trientine encapsulated alginate nanoparticles for copper toxicity induced hepatocerebral diseases: A preliminary study,"Background and Aims: Trientine is unable to mitigate the brain copper overload and neurological manifestations in Wilson's disease patients. The aim of this study was to assess the therapeutic efficacy of orally administered Trientine loaded nanoparticles (7.2mg Trientine/200g body-weight/day) to that of conventional Trientine (14.4mg Trientine/200g body-weight/day) for 90 days in Wistar rat model for non-Wilsonian brain copper toxicosis. Methods: High performance liquid chromatography, atomic absorption spectrophotometry, biochemical estimations, neurobehavioral and histopathological studies, and nanoparticles preparation and their physicochemical characterization were carried out. Results: Trientine nanoparticles exhibited mean 351 nm size and less than 34% of Trientine release. Pharmacokinetics studies showed augmented levels of Trientine in brain of nanoparticles based Trientine delivery group compared to conventional Trientine delivery group. Conventional and nanoparticles based Trientine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary Cu levels, and acetylcholinesterase activity in rat model of Cu toxicosis. Conventional Trientine therapy resulted in negative rhodanine staining of liver and brain sections corroborated by 63%, and16% reduction in hepatic and brain copper content, respectively compared to non-treated Cu-intoxicated group. However, liver and brain sections of nanoparticles based Trientine therapy group demonstrated grade 1 copper, and no copper depositions substantiated by 46% and 28% reduction in hepatic and brain copper content, respectively in comparison to non-treated copperintoxicated group. Conclusions: Taken together, the present study reveals the first in vivo evidence for therapeutic efficacy of Trientine nanoparticles in chelating more brain copper and alleviating neurological deficits even at half the dose as given in conventional Trientine therapy.",liver;hepatic encephalopathy;toxicity;chelation;brain;therapy;rat model;rat;intoxication;Wistar rat;human;patient;high performance liquid chromatography;pharmacokinetics;histopathology;memory;atomic absorption spectrometry;staining;Wilson disease;trientine;alginic acid;nanoparticle;copper;rhodanine;acetylcholinesterase,"Pal, A.;Prasad, R.;Vasishta, R. K.;Thapa, B. R.",2014,April,http://dx.doi.org/10.1016/S0168-8278%2814%2961405-7,0,0,
1463,Wilson's disease-experience at Istanbul Faculty of Medicine O,"Introduction: Wilson's disease is an autosomal recessive disorder characterized by neuropsychiatric and hepatic symptoms associated with positive copper balance. It is possible to improve survival and quality of life with chelation therapy, even during a decompensated stage. Material and methods: In this single-center study, we shared the 20-year experience with regards to diagnosis and treatment of 194 cases (156 indices) diagnosed according to EASL 2012 Wilson's disease criteria. Patients presenting with acute liver failure were excluded and all possible causes of liver disease were investigated. Results: 56.7 % (110) of all patients were male, with a mean age of 22.3 +/- 10 years at the time of diagnosis, with a delay in diagnosis of 19 +/- 33 (0-168) months. 35.7 % of all patients had hepatic form, 20.7 % had neurological form and 28.9 % had hepatoneurologic form. 14.7 % of patients were asymptomatic. Screening family members revealed 38 patients, out of which, 24 % had compensated liver cirrhosis and 39.5 % had normal findings. HBsAg positivity was 3.1 %, Anti-HCV 0.5 %, respectively. Patients had low serum ceruloplasmin levels (<20 mg /dL) 86 %, elevated 24-h urine copper output (> 100 mcg) 89.9 % and elevated hepatic copper (> 250 mcg / g) 84.7 %. During the course of treatment, ceruloplasmin levels decreased in 89 % of the patients and were below the diagnostic cutoff (p <0.05). More common in patients with neurological signs, 65.7 % had Kayser Fleischer ring. Serum albumin levels increased, transaminase levels decreased, prothrombin time shortened and clinical ascites disappeared significantly with treatment. Four people with drug noncompliance developed neurological symptoms. 10 patients had their D-penicillamine treatment switched to trientine due to increased neurological symptoms. During follow-up we lost 15 patients due to drug noncompliance; one patient due to duodenal variceal bleeding, and one patient due to sepsis (D-penicillamine treatment increased transfer dysphagia and caused aspiration pneumonia) 315 siblings of 93 index cases were screened. Secondary tests were ordered in 89 cases because a diagnostic criterion was met. The parents of 46.4 % had intra-familial marriages. Conclusion: Multiple copper metabolism markers should be used in the diagnosis of Wilson's disease, and family members must be tested. With the right treatment, prognosis is excellent.",liver;Asian;Turkey (republic);human;patient;diagnosis;neurologic disease;copper metabolism;liver disease;acute liver failure;chelation therapy;aspiration pneumonia;marriage;prothrombin time;sepsis;quality of life;urine;ceruloplasmin blood level;male;follow up;bleeding;dysphagia;survival;sibling;parent;prognosis;liver cirrhosis;screening;ascites;autosomal recessive disorder;penicillamine;copper;ceruloplasmin;serum albumin;aminotransferase;hepatitis B surface antigen;trientine;marker,"Soyer, Z. M.;Demir, K.;Karaca, C.;Basar, R.;Akyuz, F.;Kaymakoglu, S.;Besisik, F.;Okten, A.",2014,March,http://dx.doi.org/10.1007/s12072-014-9519-7,0,1,
1464,Low albumin and high alanine transaminases is helpful in prediction of poor outcome on medical therapy in Wilsonian chronic liver disease (CLD)?,"Introduction: New Wilson's index is not a reliable predictor of the outcome in Wilsonian chronic liver disease. The aim of this study was to look at the predictive risk factors for poor outcome in the Wilson's disease presenting as chronic liver disease. Methods: Wilson's disease (WD) presenting as CLD were managed with D-Pencillamine (10-20 mg/kg/day) and Zinc combination therapy. Univariate and multivariate analysis was done to see the association of the risk factors with poor outcome (Liver transplantation or death) at the time of diagnosis. Results: Thirty three cases presented in last 3 years. Five of 7 presenting as acute on chronic liver failure (ACLF), 6 of 20 as decompensated CLD had poor outcome. All 6 compensated CLD, 2 of 7 ACLF and 14 of 20 with decompensated CLD improved. On univariate analysis, bilirubin, AST, ALT, Child Pughs score and New Wilson's index score were significantly higher in those with poor outcome. On logistic regression analysis significant association with poor outcome were high ALT (adjusted OR 1.062, 95 % CI 1.007-1.12, p = 0.015) and low albumin (adjusted OR 0.052, 95 % CI 0.005-0.56, p = 0.028) was seen. With 20 IU increase in ALT odd's ratio increases by 3.3 (95 % CI 1.15 to 9.58) and 1 gram decrease in albumin increases the odd's ratio by 0.95 (95 % CI 0.44-0.995). Conclusion: High ALT and low albumin are independently associated with poor outcome on medical therapy in WD presenting as CLD. Child Pugh's and New Wilson's index scores did not show significant association with poor outcome.",prediction;therapy;chronic liver disease;Asian;liver;human;child;risk factor;acute on chronic liver failure;logistic regression analysis;liver transplantation;multivariate analysis;univariate analysis;Wilson disease;diagnosis;death;albumin;alanine aminotransferase;bilirubin;zinc,"Alam, S.;Khanna, R.;Sood, V.;Rawat, D.",2014,March,http://dx.doi.org/10.1007/s12072-014-9519-7,0,0,
1465,Report of the ASFA apheresis registry study on wilson's disease,"Purpose: Wilson's disease is a rare autosomal recessive genetic disorder (1:30,000) of the ATP7B gene that results in copper accumulation in the liver, brain, cornea and kidney. Even though there are available treatment options such as low-copper diets, zinc acetate, tetrathiomolybdate and copper chelation, patients may still present in crisis either before their disease is diagnosed, or after diagnosis due to ineffectiveness or intolerance to current therapy. Patients with Wilson's disease crisis often present with fulminant hepatic failure, severe DAT-negative hemolytic anemia and multiorgan failure, with rapid clinical deterioration. Eventually many patients require liver transplantation. In this setting, therapeutic plasma exchange (TPE) has been used to remove copper and provide a bridge to liver transplantation. Most studies describing the use plasma exchange for Wilson's disease have been case reports. Here we report the collective experiences through the ASFA apheresis registry on Wilson's disease. Methods: The ASFA apheresis registry study is a multicenter registry study. Both prospective and retrospective data with the latter involving data collection back to January 2000 are allowed in the registry. Study data were collected and managed using REDCap electronic data capture tools hosted at Children's National Health System. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies. The registry includes patient demographic and clinical information, apheresis procedural information, treatment schedule, and treatment outcome/complications. All participating sites had obtained approval from the ASFA apheresis registry subcommittee of the ASFA Applications committee as well as from local IRBs. Results: To date, a total of 10 patients (three males and seven females) with Wilson's disease treated between 2005 and 2013 were included in this study. Median age of first diagnosis was 16- years-old (range 6-30 years). Median age at first TPE was 17 years (range 6-61 years). The patients underwent a total of 43 TPEs with most of patients requiring an intensive session of TPE. Median number of TPE procedures was 3.5 (range 1-9). Other than one patient who had received one TPE before the patient was transferred to the study site, no patient received TPE prior to the first registry study TPE. All of the TPEs used ACD-A as anticoagulation, 98% (42/43) TPEs targeted 1-1.25 plasma volumes, and 95% (41/43) TPEs were performed with 100% fluid balance. All patients had a central line placed for TPE. Post TPE, 90% (9/ 10) patients underwent liver transplantation, all 10 patients (transplanted as well no transplanted) have at least a 6-month survival. Conclusion: All 10 patients with Wilson's disease who underwent plasma exchange had a positive outcome in terms of 6- month survival. As a first report of the ASFA apheresis registry study, we demonstrated the value of using this registry to collect apheresis related patient outcome from multiple centers.",apheresis;society;register;Wilson disease;human;patient;plasmapheresis;liver transplantation;survival;diagnosis;gene;fulminant hepatic failure;genetic disorder;therapy;central venous catheter;kidney;fluid balance;hemolytic anemia;male;cornea;autosomal recessive inheritance;female;chelation;brain;child;information processing;public health;health care;procedures;anticoagulation;plasma volume;liver;case report;deterioration;diet;multiple organ failure;copper;tetrathiomolybdic acid;zinc acetate,"Wu, Y.;Pham, H. P.;Morgan, S.;Yamada, C.;Cooling, L.;Kim, H. C.;Schneiderman, J.;Sachais, B.;Schwartz, J.;Winters, J. L.;Hofmann, J.;Pagano, M.;Wong, E. C. C.",2014,February,http://dx.doi.org/10.1002/jca.21314,0,1,
1466,Outcome and development of symptoms after orthotopic liver transplantation for Wilson disease,"Background: Wilson disease (WD) is an autosomal recessive copper storage disease resulting in hepatic and neurologic dysfunction. Liver transplantation is an effective treatment for fulminant cases for patients with chronic liver disease. Reports on the outcome of neuropsychiatric symptoms after orthotopic liver transplantation (OLT) are limited. Aim: To assess the course of neuropsychiatric and hepatic symptoms after liver transplantation for Wilson disease Methods: Nineteen patients with Wilson disease received liver transplantation and were followed prospectively from 2005 to 2010 for the development of hepatic, neurological and psychiatric symptoms. Results: Eight patients (all female) were transplanted for acute liver failure and eleven patients for chronic liver failure. Patient survival rates one and five yr after transplantation were 78% and 65%, respectively. Of the surviving patients, hepatic symptom scores improved in all patients and neurological symptom scores improved in all but one patient after OLT compared to the time of initial diagnosis and compared to pre-OLT status. Psychiatric symptoms showed moderate improvements. Conclusion: Survival after OLT for Wilson disease with end-stage liver disease is excellent. Overall, neuropsychiatric symptoms improved after transplantation, substantiating arguments for widening of the indication for liver transplantation in symptomatic neurologic Wilson disease patients with stable liver function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",atp7b;Copper;Neurologic deterioration;Orthotopic liver transplantation;Wilson's disease;adult;article;ATP7B gene;cause of death;ceruloplasmin blood level;clinical article;copper metabolism;disease course;female;follow up;gene;gene mutation;genotype;graft failure/co [Complication];graft failure/su [Surgery];graft survival;heart right ventricle failure/co [Complication];histopathology;human;laboratory test;liver failure/co [Complication];liver failure/su [Surgery];liver function;liver graft rejection/co [Complication];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver graft rejection/su [Surgery];liver transplantation;male;medical record review;neurological complication/co [Complication];orthotopic transplantation;priority journal;prospective study;rating scale;reoperation;scoring system;sepsis/co [Complication];survival rate;symptom;treatment outcome;Unified Wilson Disease Rating Scale;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];azathioprine/dt [Drug Therapy];ceruloplasmin;copper/to [Drug Toxicity];cyclosporin A/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Weiss, K. H.;Schafer, M.;Gotthardt, D. N.;Angerer, A.;Mogler, C.;Schirmacher, P.;Schemmer, P.;Stremmel, W.;Sauer, P.",2013,November/December,http://dx.doi.org/10.1111/ctr.12259,0,0,
1467,"Iron, zinc, and copper in retinal physiology and disease","The essential trace metals iron, zinc, and copper play important roles both in retinal physiology and disease. They are involved in various retinal functions such as phototransduction, the visual cycle, and the process of neurotransmission, being tightly bound to proteins and other molecules to regulate their structure and/or function or as unbound free metal ions. Elevated levels of ""free"" or loosely bound metal ions can exert toxic effects, and in order to maintain homeostatic levels to protect retinal cells from their toxicity, appropriate mechanisms exist such as metal transporters, chaperones, and the presence of certain storage molecules that tightly bind metals to form nontoxic products. The pathways to maintain homeostatic levels of metals are closely interlinked, with various metabolic pathways directly and/or indirectly affecting their concentrations, compartmentalization, and oxidation/reduction states. Retinal deficiency or excess of these metals can result from systemic depletion and/or overload or from mutations in genes involved in maintaining retinal metal homeostasis, and this is associated with retinal dysfunction and pathology. Iron accumulation in the retina, a characteristic of aging, may be involved in the pathogenesis of retinal diseases such as age-related macular degeneration (AMD). Zinc deficiency is associated with poor dark adaptation. Zinc levels in the human retina and RPE decrease with age in AMD. Copper deficiency is associated with optic neuropathy, but retinal function is maintained. The changes in iron and zinc homeostasis in AMD have led to the speculation that iron chelation and/or zinc supplements may help in its treatment. © 2013 Elsevier Inc.",Age-related macular degeneration;Copper;Iron;Iron chelators;Metal homeostasis interactions;Retina;Trace metal deficiency and overload;Trace metal toxicity;Zinc;Zinc supplements;aceruloplasminemia;autosomal recessive disorder;cell metabolism;copper deficiency;copper metabolism;disease association;dose response;drug effect;drug megadose;drug safety;eye toxicity;Friedreich ataxia;gene mutation;hemochromatosis;human;iron deficiency;iron induced retinal toxicity;iron metabolism;iron overload;Menkes syndrome;mitochondrial respiration;nephrotoxicity/si [Side Effect];nonhuman;physiological process;priority journal;retina disease;retina macula age related degeneration/dt [Drug Therapy];review;visual disorder;visual impairment/dt [Drug Therapy];Wilson disease;zinc metabolism;agents acting on the eye/ct [Clinical Trial];agents acting on the eye/dt [Drug Therapy];agents acting on the eye/po [Oral Drug Administration];alpha tocopherol/ct [Clinical Trial];alpha tocopherol/cb [Drug Combination];alpha tocopherol/dt [Drug Therapy];ascorbic acid/ct [Clinical Trial];ascorbic acid/cb [Drug Combination];ascorbic acid/dt [Drug Therapy];beta carotene/ct [Clinical Trial];beta carotene/cb [Drug Combination];beta carotene/dt [Drug Therapy];copper/ec [Endogenous Compound];cupric oxide/ct [Clinical Trial];cupric oxide/cb [Drug Combination];cupric oxide/dt [Drug Therapy];deferasirox/dt [Drug Therapy];deferiprone/dt [Drug Therapy];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/dt [Drug Therapy];deferoxamine/im [Intramuscular Drug Administration];iron/ec [Endogenous Compound];placebo;unclassified drug;zinc/ec [Endogenous Compound];zinc monocysteine complex/ct [Clinical Trial];zinc monocysteine complex/dt [Drug Therapy];zinc monocysteine complex/po [Oral Drug Administration];zinc oxide/ct [Clinical Trial];zinc oxide/cb [Drug Combination];zinc oxide/do [Drug Dose];zinc oxide/dt [Drug Therapy];zinc sulfate/ct [Clinical Trial];zinc sulfate/dt [Drug Therapy],"Ugarte, M.;Osborne, N. N.;Brown, L. A.;Bishop, P. N.",2013,November,http://dx.doi.org/10.1016/j.survophthal.2012.12.002,0,0,
1468,Wilson's disease. [Czech],"Wilson's disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilson's disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilson's disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The diagnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, Kayser-Fleischer ring). The diagnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilson's disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.",D-penicillamine;Treatment;Wilson's disease;Zinc;article;ceruloplasmin blood level;clinical feature;copper blood level;dysarthria;gene mutation;human;muscle contraction;rigidity;survival rate;Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound],"Marecek, Z.;Bruha, R.",2013,,,0,0,
1469,Central pontine myelinolysis associated with Wilson disease in a 7-year-old child,"Wilson disease is a rare heredodegenerative inborn error of copper metabolism with varied neuropsychiatric, hepatic and other manifestations. Here we report a case of Wilson disease with neurological manifestations in a 7-year-old girl with concurrent asymptomatic liver involvement and characteristic radiological findings of signal intensity alterations in bilateral striata and thalami along with changes in central pons too like central pontine myelinolysis (CPM), which is of rare occurrence. Copyright 2013 BMJ Publishing Group. All rights reserved.",article;aspartate aminotransferase blood level;case report;central pontine myelinolysis/di [Diagnosis];ceruloplasmin blood level;child;diet therapy;differential diagnosis;disease association;dysphagia;eye disease/di [Diagnosis];face disorder;facial expression;female;foot disease;generalized dystonia/dt [Drug Therapy];hand disease;human;hypersalivation;motor dysfunction;muscle rigidity;nuclear magnetic resonance imaging;oromandibular dystonia;potassium blood level;priority journal;reflex disorder;school child;slit lamp;sodium blood level;speech disorder;splenomegaly;vein dilatation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];elemental zinc/cb [Drug Combination];elemental zinc/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];potassium/ec [Endogenous Compound];sodium/ec [Endogenous Compound];trihexyphenidyl/dt [Drug Therapy];unclassified drug;zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Verma, R.;Rai, D.",2013,,http://dx.doi.org/10.1136/bcr-2012-007408,0,0,
1470,Wilson disease in offspring of affected patients: Report of four French families,"Background: Wilson disease (WD) is an autosomal recessive genetic disorder caused by mutations in the ATP7B gene resulting in toxic accumulation of copper mainly in the liver and brain. Early treatment may prevent irreversible tissue damage. Aim: We report on four families with an occurrence of WD in two consecutive generations in order to highlight the need for screening offspring of affected parents. Results: In all families, one parent was known to be affected with WD. Screening for the disease was not performed in children from two families until occurrence of liver disease in one and of neurological symptoms in the other. In two other families, screening of children as soon as diagnosis was performed in the affected parent allowed a timely rescue of advanced liver disease in one while two affected children were asymptomatic. In three children, diagnosis required direct sequencing of the ATP7B gene. Two novel disease-causing mutations are reported. Conclusion: Patients with WD should be offered genetic counselling when considering pregnancy and offspring should always be screened for the disease. Diagnostic difficulties based on copper disturbances in asymptomatic children that are obligate carriers of the Wilson gene and the usefulness of molecular diagnosis are discussed. © 2013 Elsevier Masson SAS.",adolescent;adult;aminotransferase blood level;article;bilirubin blood level;ceruloplasmin blood level;chronic graft rejection/co [Complication];chronic graft rejection/su [Surgery];clinical article;consanguinity;copper metabolism;DNA sequence;dysarthria;dysphonia;dystonia;familial disease;female;frameshift mutation;France;fulminant hepatic failure/su [Surgery];gait disorder;gene mutation;gene sequence;genetic counseling;haplotype;hemolytic anemia;heterozygote;human;learning disorder;leukopenia;liver cirrhosis;liver disease;liver function test;liver transplantation;male;medical history;microsatellite marker;molecular diagnosis;mutational analysis;neurologic disease;parent;physical examination;pregnancy;progeny;screening;slit lamp;thrombocytopenia;tissue injury;Wilson disease;bilirubin;ceruloplasmin;copper;penicillamine;Wilson disease protein/ec [Endogenous Compound],"Dufernez, F.;Lachaux, A.;Chappuis, P.;De Lumley, L.;Bost, M.;Woimant, F.;Misrahi, M.;Debray, D.",2013,June,http://dx.doi.org/10.1016/j.clinre.2013.01.001,0,0,
1471,"Case 2: A teenager with nausea, vomiting and dysarthria",,adolescent;airway obstruction;article;brain atrophy;case report;ceruloplasmin blood level;chelation therapy;coarse liver;copper metabolism;degenerative disease/di [Diagnosis];demyelinating disease/di [Diagnosis];diet restriction;differential diagnosis;disease duration;disorders of mitochondrial functions/di [Diagnosis];dysarthria;electron microscopy;fatigue;gastrocnemius muscle;gene mutation;hand tremor;hepatitis;human;hypersalivation;hyperthyroidism/di [Diagnosis];liver biopsy;liver disease;liver fibrosis;male;metabolic disorder/di [Diagnosis];muscle cramp;nausea;neurologic examination;nuclear magnetic resonance imaging;parkinsonism/di [Diagnosis];slit lamp;splenomegaly;staining;steatosis;urinary excretion;vomiting;weakness;weight reduction;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper;Wilson disease protein;zinc/po [Oral Drug Administration],"Raiman, J. A. J.;Atkinson, C.;Kamath, B. M.;Mandelcorn, J.;Cutz, E.",2013,December,,0,0,
1472,Recent advances in the management of choreas,"The management of patients with chorea, in particular Huntington's disease, is a complex task requiring skills in a number of areas. This paper reviews new knowledge on this topic and places it in the context of established procedures. It is focused on Huntington's disease, since this is the disorder, for which most publications on management have been published in the past few years. Management starts with appropriate diagnosis and differential diagnosis, with the aim of finding disorders with chorea amenable to causative treatment. The place of genetic testing and the importance of genetic counselling is stressed, as well as the importance of precise observation in the course of the disorder to tailor appropriate therapies. Pharmacological treatment is based on poor evidence but to a large extent on expertise from centres devoted to the care of patients with Huntington's disease. It is focused mainly on motor and psychiatric aspects of the phenotype. Nonpharmacological treatment is important and is best offered in a multidisciplinary care setting. © The Author(s), 2013.",Chorea;diagnosis;Huntington's disease;management;treatment;anamnesis;chorea/dt [Drug Therapy];chorea/si [Side Effect];chorea/di [Diagnosis];clinical feature;cognitive defect/dt [Drug Therapy];cognitive defect/th [Therapy];cognitive therapy;depression/dt [Drug Therapy];genetic counseling;genetic screening;human;Huntington chorea/dt [Drug Therapy];mental disease/dt [Drug Therapy];mental disease/th [Therapy];motor dysfunction;neurologic examination;Parkinson disease/dt [Drug Therapy];phenotype;priority journal;psychopharmacotherapy;review;tardive dyskinesia/si [Side Effect];unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];amantadine/dt [Drug Therapy];anticonvulsive agent/ae [Adverse Drug Reaction];antidepressant agent/dt [Drug Therapy];calcium channel blocking agent/ae [Adverse Drug Reaction];carbamazepine/dt [Drug Therapy];contraceptive agent/ae [Adverse Drug Reaction];dimebon/dt [Drug Therapy];dopamine receptor blocking agent/ae [Adverse Drug Reaction];levodopa/ae [Adverse Drug Reaction];levodopa/dt [Drug Therapy];nabilone/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];olanzapine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];psychostimulant agent/ae [Adverse Drug Reaction];riluzole/dt [Drug Therapy];risperidone/dt [Drug Therapy];serotonin uptake inhibitor/dt [Drug Therapy];tetrabenazine/ct [Clinical Trial];tetrabenazine/dt [Drug Therapy];tiapride/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Burgunder, J. M.",2013,March,http://dx.doi.org/10.1177/1756285612471700,0,0,
1473,"Repurposing as a strategy for orphan drug development, evidence from European approvals","Introduction: Increased awareness of the value of drug repurposing has led to a number of initiatives to make discarded drug candidates available for screening. Repurposing has been suggested to be of considerable use in identifying drugs for the treatment of rare diseases. The 78 orphan drugs approved in Europe provide a useful set to analyze for evidence of repurposing. Areas covered: Orphan drugs approved in Europe were classified as having been repurposed, as representing drugs specifically developed for orphan indications, or into those drugs that had been classified as orphan drugs after their utility had been established. Drugs were also classified as novel medical entities, biological products and natural products. The majority (60%) of approvals were of novel medical entities, including 17 of the 19 approved biological products. Natural products provided 10 of the approved drugs while 30 (38%) of the approvals were drugs repurposed from other indications. Expert opinion: Identifying drugs for the treatment of rare diseases requires cost-effective discovery approaches. As the prevalence or incidence of the disease decreases, the need for lower cost approaches becomes more important. The systematic use of repurposing provides better opportunities for meeting such goals, and can facilitate subsequent development of the resulting drug(s). © Informa UK, Ltd.","Development strategy;Europe;Orphan drugs;Repurposing;acute lymphoblastic leukemia;cost effectiveness analysis;drug approval;drug development;drug repositioning;enzyme replacement;gene therapy;hematopoietic stem cell;human;incidence;prevalence;promyelocytic leukemia;rare disease;review;severe myoclonic epilepsy in infancy;Wilson disease;3,4 diaminopyridine;aminolevulinic acid;arsenic trioxide;azacitidine;betaine;bosentan;brentuximab vedotin;bromelain;busulfan;canakinumab;carglumic acid;eculizumab;hydroxyurea;imatinib;mannitol;mercaptopurine;ofatumumab;omega conotoxin MVIIA;orphan drug;pirfenidone;protein;sapropterin;sildenafil;stiripentol;tetrahydrobiopterin;thalidomide;thiotepa;trabectedin;unindexed drug;zinc acetate","Norman, P.",2013,,http://dx.doi.org/10.1517/21678707.2013.796883,0,0,
1474,Liver diseases in pregnancy: Diseases not unique to pregnancy,"Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.",Adenoma;Autoimmune;Cirrhosis;Gallstones;Liver;Pregnancy;Viral hepatitis;autoimmune hepatitis/dt [Drug Therapy];Budd Chiari syndrome;delta agent hepatitis;drug dose reduction;endoscopic retrograde cholangiopancreatography;esophagus varices;gallstone/su [Surgery];hepatic encephalopathy/dt [Drug Therapy];hepatitis A;hepatitis B/dt [Drug Therapy];hepatitis C;hepatitis E;herpes simplex;human;hypertransaminasemia;liver adenoma/su [Surgery];liver cell carcinoma/su [Surgery];liver disease/dt [Drug Therapy];nonhuman;portal hypertension/dt [Drug Therapy];portal hypertension/th [Therapy];portal vein thrombosis;primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis;radiofrequency ablation;review;sclerotherapy;sodium restriction;teratogenicity/si [Side Effect];vertical transmission;Wilson disease/dt [Drug Therapy];adefovir dipivoxil/dt [Drug Therapy];alpha2b interferon/dt [Drug Therapy];azathioprine/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];boceprevir/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];entecavir/dt [Drug Therapy];furosemide/dt [Drug Therapy];lactulose/dt [Drug Therapy];lamivudine/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester/dt [Drug Therapy];nadolol/dt [Drug Therapy];peginterferon/dt [Drug Therapy];peginterferon alpha2a;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];propranolol/dt [Drug Therapy];rapamycin/dt [Drug Therapy];recombinant alpha2b interferon;ribavirin/dt [Drug Therapy];rifaximin/dt [Drug Therapy];spironolactone/dt [Drug Therapy];steroid/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];telaprevir/dt [Drug Therapy];telbivudine/dt [Drug Therapy];tenofovir/dt [Drug Therapy];tenofovir disoproxil;thymocyte antibody/dt [Drug Therapy];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Almashhrawi, A. A.;Ahmed, K. T.;Rahman, R. N.;Hammoud, G. M.;Ibdah, J. A.",2013,,http://dx.doi.org/10.3748/wjg.v19.i43.7630,0,0,
1475,Update on Wilson Disease,"Wilson disease (WD) is an inherited disorder of chronic copper toxicosis characterized by excessive copper deposition in the body, primarily in the liver and the brain. It is a progressive disease and fatal if untreated. Excessive copper accumulation results from the inability of liver to excrete copper in bile. Copper is an essential trace metal and has a crucial role in many metabolic processes. Almost all of the body copper is protein bound. In WD, the slow but relentless copper accumulation overwhelms the copper chaperones (copper-binding proteins), resulting in high levels of free copper and copper-induced tissue injury. Liver is the central organ for copper metabolism, and copper is initially accumulated in the liver but over time spills to other tissues.WD has protean clinical manifestations mainly attributable to liver, brain, and osseomuscular impairment. Diagnosis of WD is challenging and based on combination of clinical features and laboratory tests. Identification of various high-frequency mutations identified in different population studies across the world has revived interest in developing DNA chips for rapid genetic diagnosis of WD.All symptomatic and all presymptomatic patients require lifelong decoppering with careful clinical tracking. Decoppering ensures that presymptomatic individuals remain symptom free. With judicious decoppering, given time, even patients with severe neurological disability improve and can return to normal life and resume school or work at par with their peers. Treatment regimens and tracking patients using the WD-specific Global Assessment Scale for WD (GAS for WD) are discussed. © 2013 Elsevier Inc.",ATP7B gene;Copper;Decoppering;Global Assessment Scale for WD (GAS for WD);Hepatocellular degeneration;Kayser-Fleischer rings;Penicillamine;Trientine;Wilson disease;Zinc;adverse outcome;allergic reaction/si [Side Effect];amino acid substitution;arthropathy;article;asymptomatic disease;behavior disorder;bleeding/si [Side Effect];bone disease;ceruloplasmin gene;clinical feature;cognitive defect;copper deficiency/si [Side Effect];copper metabolism;decompensated liver cirrhosis/dt [Drug Therapy];DNA microarray;dose response;drug dose increase;drug dose titration;drug substitution;drug tolerability;drug withdrawal;elastosis/si [Side Effect];extrapyramidal syndrome;false negative result;false positive result;fulminant hepatic failure/co [Complication];gene frequency;gene identification;genotype phenotype correlation;Global Assessment Scale;Goodpasture syndrome/si [Side Effect];hematologic disease;hemolytic anemia/si [Side Effect];homeostasis;human;incidental finding;iron overload/si [Side Effect];missense mutation;mutational analysis;myasthenia gravis/si [Side Effect];nephrotic syndrome/si [Side Effect];optic neuritis/si [Side Effect];outcome assessment;priority journal;protein blood level;rating scale;sideroblastic anemia/si [Side Effect];skin bruising/si [Side Effect];stomach irritation/si [Side Effect];systemic lupus erythematosus/si [Side Effect];thrombocytopenia/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];carbidopa plus levodopa/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];cholinergic receptor blocking agent/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];gluconate zinc/dt [Drug Therapy];Menkes protein/ec [Endogenous Compound];neuroleptic agent/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];Wilson disease protein/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc acetate/cm [Drug Comparison];zinc acetate/dt [Drug Therapy];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy],"Aggarwal, A.;Bhatt, M.",2013,,http://dx.doi.org/10.1016/B978-0-12-410502-7.00014-4,0,0,
1476,Stagnant loop syndrome: A rare cause of severe malabsorption,"Background: Intestinal bacterial overgrowth as a consequence of postsurgical anatomical abnormalities as well as other small bowel diseases can lead to malabsorption. Case Report: A female patient had several abdominal operations due to recurrent intestinal obstructions. Initially, she presented with severe megaloblastic anaemia. Subsequently, she suffered from weight loss, diarrhoea, oedema, recurrent anaemia (despite vitamin B12 substitution), and severe malabsorption of proteins, lipids, iron, and vitamins. Vague information about the performed surgeries, an anatomy of the bowel that was difficult to interpret, and an unusual cholestasis made it difficult to reach the diagnosis of bacterial overgrowth due to a stagnant loop syndrome. Treatment with antibiotics only temporarily improved the condition of the patient. After restoring bowel continuity and after the resection of an enteroenteric fistula as well as of a bowel conglomerate, the patient did not show any further symptoms. Conclusion: The history of this patient indicates that the diagnosis of a stagnant loop syndrome may be difficult. The primary goal regarding surgically created small intestinal bacterial overgrowth should be the correction of the underlying small intestinal abnormality, whenever possible. © 2013 S. Karger GmbH, Freiburg.",Anaemia;Malnutrition;Small bowel overgrowth;Stagnant loop syndrome;abdominal surgery;adult;alkaline phosphatase blood level;article;bacterial overgrowth;blind loop syndrome;blood chemistry;body weight;case report;cholestasis;colonoscopy;copper blood level;cyanocobalamin deficiency;diarrhea;disease severity;duodenitis;edema;endoscopic retrograde cholangiopancreatography;eradication therapy;Escherichia coli;female;ferritin blood level;gastritis;gastroscopy;hormonal contraception;human;ileocecal valve;intestine obstruction;iron blood level;iron deficiency;laboratory test;liver biopsy;malabsorption;mean corpuscular hemoglobin;megaloblastic anemia;microbiological examination;primary sclerosing cholangitis;protein blood level;recurrent disease;short bowel syndrome;tachycardia;treatment duration;weight reduction;Wilson disease;alkaline phosphatase/ec [Endogenous Compound];amoxicillin/ec [Endogenous Compound];C reactive protein/ec [Endogenous Compound];ceftriaxone;copper/ec [Endogenous Compound];cyanocobalamin;ferritin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];lipid;metronidazole;omeprazole;protein;vitamin;xylose;zinc/ec [Endogenous Compound],"Herfarth, C.;Weigand, K.",2013,June,http://dx.doi.org/10.1159/000353524,0,0,
1477,A case of colonic adenocarcinoma in a patient with wilson's disease,"Wilson's disease (WD) is an autosomal recessive inherited disorder of copper metabolism that results in the accumulation of copper in the body and primarily in the liver, brain, and cornea. Copper is a toxic metal and might be associated with cancer induction. Most malignancies associated with WD are hepatocellular carcinoma and cholangiocarcinoma. Other intra-abdominal malignancies have been only rarely reported. To our knowledge, this is the first report to suggest that patients with WD may be vulnerable to a malignant change in the colonic mucosa during long-term copper chelating therapy. We report a case of colonic adenocarcinoma in a patient with WD and review the related literature.",Adenocarcinoma;Colon;Copper;Hepatolenticular degeneration;Malignancy;abdominal pain;adult;article;cancer staging;case report;colon adenocarcinoma/di [Diagnosis];colon adenocarcinoma/su [Surgery];colonoscopy;computer assisted emission tomography;computer assisted tomography;constipation;hemicolectomy;histopathology;human;human tissue;immunohistochemistry;laboratory test;laparotomy;male;slit lamp;Wilson disease/dt [Drug Therapy];fluorodeoxyglucose f 18;penicillamine/dt [Drug Therapy],"Lee, S. Y.;Kim, I. H.;Yoo, S. H.;Kim, D. G.",2013,July,http://dx.doi.org/10.5009/gnl.2013.7.4.500,0,0,
1478,Nutrients for Prevention and Treatment of Mental Health Disorders,"The choice of nutrients for review is based on clinical evidence of efficacy in neuropsychiatric disorders and biochemical effects that are neuroprotective or reparative. Vitamins, minerals, amino acids, and metabolites have been shown to augment antidepressants, improve symptoms in anxiety disorders, depression, neurodegenerative diseases, brain injury, ADHD, and schizophrenia, and to reduce medication side effects. Detection and correction of vitamin and mineral deficiencies can be essential for recovery. Generally low in adverse effects when taken in therapeutic doses, nutrients can be combined for greater benefits. Further studies are warranted to validate these promising treatments. © 2013 Elsevier Inc.",gamma-Aminobutyric acid;5-Hydroxy-l-tryptophan;Choline;Inositol;Minerals;N-Acetylcysteine;Neuroprotection;Vitamins;anxiety disorder;attention deficit disorder/dt [Drug Therapy];bipolar disorder/dt [Drug Therapy];brain injury;cannabis addiction/dt [Drug Therapy];cocaine dependence/dt [Drug Therapy];cognitive defect/si [Side Effect];degenerative disease;dementia;depression/dt [Drug Therapy];diarrhea/si [Side Effect];diet supplementation;disease association;dizziness/si [Side Effect];drug hypersensitivity/si [Side Effect];drug induced headache/si [Side Effect];drug intoxication/dt [Drug Therapy];environmental exposure;generalized anxiety disorder/dt [Drug Therapy];human;insomnia/si [Side Effect];major depression/dt [Drug Therapy];mental disease;mental health;metabolite;mineral deficiency;nausea/si [Side Effect];neuropsychiatry;nutrient management;nutritional assessment;obsessive compulsive disorder/dt [Drug Therapy];outcome assessment;practice guideline;priority journal;randomized controlled trial (topic);review;schizophrenia;sexual dysfunction;somnolence/si [Side Effect];substance abuse;vitamin deficiency;vomiting/si [Side Effect];Wilson disease;4 aminobutyric acid;5 hydroxytryptophan/ae [Adverse Drug Reaction];5 hydroxytryptophan/ct [Clinical Trial];5 hydroxytryptophan/cb [Drug Combination];5 hydroxytryptophan/cm [Drug Comparison];5 hydroxytryptophan/dt [Drug Therapy];5 hydroxytryptophan/to [Drug Toxicity];acetylcysteine;acetylcysteine derivative/ae [Adverse Drug Reaction];acetylcysteine derivative/ct [Clinical Trial];acetylcysteine derivative/dt [Drug Therapy];acetylcysteine derivative/to [Drug Toxicity];acetylcysteine derivative/iv [Intravenous Drug Administration];acetylcysteine derivative/po [Oral Drug Administration];alprazolam/ct [Clinical Trial];alprazolam/cm [Drug Comparison];alprazolam/dt [Drug Therapy];antidepressant agent;clomipramine/dt [Drug Therapy];colecalciferol;copper;gluconate zinc/ct [Clinical Trial];gluconate zinc/cb [Drug Combination];gluconate zinc/cm [Drug Comparison];gluconate zinc/dt [Drug Therapy];iron;lorazepam/ct [Clinical Trial];lorazepam/cm [Drug Comparison];lorazepam/dt [Drug Therapy];methylphenidate/ct [Clinical Trial];methylphenidate/cb [Drug Combination];methylphenidate/cm [Drug Comparison];methylphenidate/dt [Drug Therapy];monoamine oxidase inhibitor/cb [Drug Combination];monoamine oxidase inhibitor/dt [Drug Therapy];nialamide/dt [Drug Therapy];nomifensine/dt [Drug Therapy];paracetamol;placebo;pregabalin/ae [Adverse Drug Reaction];pregabalin/ct [Clinical Trial];pregabalin/cm [Drug Comparison];pregabalin/dt [Drug Therapy];pyridoxine;serotonin uptake inhibitor/cb [Drug Combination];serotonin uptake inhibitor/cm [Drug Comparison];serotonin uptake inhibitor/dt [Drug Therapy];thiamine;tryptophan;unindexed drug;venlafaxine/ct [Clinical Trial];venlafaxine/cm [Drug Comparison];venlafaxine/dt [Drug Therapy];zinc;zinc derivative/cm [Drug Comparison];zinc derivative/dt [Drug Therapy];zinc sulfide/ct [Clinical Trial];zinc sulfide/dt [Drug Therapy],"Akhondzadeh, S.;Gerbarg, P. L.;Brown, R. P.",2013,March,http://dx.doi.org/10.1016/j.psc.2012.12.003,0,0,
1479,Update in liver diseases with pregnancy,"Liver disease in pregnancy encompasses a spectrum of diseases encountered during gestation and the postpartum period that result in abnormal liver function tests, hepatobiliary dysfunction, or both. It occurs in 3% to 10% of all pregnancies.Several disorders contribute to liver disease in pregnancy. These include diseases induced by the pregnancy such as acute fatty liver of pregnancy (AFLP) and intrahepatic cholestasis of pregnancy (IHCP), diseases that existed before pregnancy that could potentially flare during pregnancy such as autoimmune hepatitis and Wilson's disease, and diseases not related to the pregnancy but that could affect the pregnant woman at any time during gestation such as viral hepatitis. © 2013 ACT.",Liver diseases;Pregnancy;acute kidney failure;adult respiratory distress syndrome;alkaline phosphatase blood level;ascites;autoimmune hepatitis;biliary tract disease;bilirubin blood level;chronic liver disease;clinical feature;computer assisted tomography;conservative treatment;corticosteroid therapy;cytomegalovirus infection;delta agent hepatitis;dialysis;diarrhea;eclampsia;Epstein Barr virus infection;fatty liver/di [Diagnosis];fatty liver/et [Etiology];gallstone;gamma glutamyl transferase blood level;HELLP syndrome/di [Diagnosis];HELLP syndrome/et [Etiology];heparinization;hepatitis A;hepatitis B;hepatitis C;hepatitis E;herpes simplex;human;hyperemesis gravidarum;intrahepatic cholestasis/di [Diagnosis];intrahepatic cholestasis/et [Etiology];jaundice;liver disease;liver failure;liver hemorrhage;liver rupture;patient counseling;plasmapheresis;preeclampsia;pregnant woman;pruritus;recurrent disease;review;solutio placentae;steatorrhea;treatment outcome;vaginal delivery;virus hepatitis;vitamin supplementation;Wilson disease;adefovir;alkaline phosphatase/ec [Endogenous Compound];azathioprine;beta adrenergic receptor blocking agent;betamethasone;bilirubin/ec [Endogenous Compound];cyclosporin;dexamethasone;entecavir;fresh frozen plasma;gamma glutamyltransferase/ec [Endogenous Compound];interferon;lamivudine;mycophenolic acid 2 morpholinoethyl ester;octreotide;penicillamine;prednisone;rapamycin;ribavirin;tacrolimus;trientine;ursodeoxycholic acid;vasopressin,"Shams, M.",2013,,http://dx.doi.org/10.6051/j.issn.2224-3992.2013.02.181,0,0,
1480,"Metabolism of triethylenetetramine and 1,12-diamino-3,6,9-triazadodecaneby the spermidine/spermine-N<sup>1</sup>-acetyltransferase and thialysine acetyltransferase","Triethylenetetramine (TETA; Syprine; Merck Rahway, NJ), a drug for Wilson's disease, is a copper chelator and a charge-deficient analog of polyamine spermidine. We recently showed that TETA is metabolized in vitro by polyamine catabolic enzyme spermidine/spermine-N<sup>1</sup>-acetyltransferase (SSAT1) and by thialysine acetyltransferase (SSAT2) to its monoacetylated derivative (MAT). The acetylation of TETA is increased in SSAT1-overexpressing mice compared with wild-type mice. However, SSAT1-deficient mice metabolize TETA at the same rate as the wild-type mice, indicating the existence of another N-acetylase respons 2ible for its metabolism in mice. Here, we show that siRNA-mediated knockdown of SSAT2 in HEPG2 cells and in primary hepatocytes from the SSAT1-deficient or wild-type mice reduced the metabolism of TETA to MAT. By contrast, 1,12-diamino-3,6,9-triazadodecane(SpmTrien), a charge-deficient spermine analog, was an extremely poor substrate of human recombinant SSAT2 and was metabolized by SSAT1 in HEPG2 cells and in wild-type primary hepatocytes. Thus, despite the similar structures of TETA and SpmTrien, SSAT2 is the main acetylator of TETA, whereas SpmTrien is primarily acetylated by SSAT1. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.","acetylation;animal cell;article;concentration (parameters);controlled study;drug mechanism;enzyme degradation;enzyme substrate;high performance liquid chromatography;human;human cell;in vitro study;liver cell;mouse;nonhuman;polyamine metabolism;priority journal;protein expression;upregulation;1,12-diamino-3,6,9-triazadodecane;acyltransferase/ec [Endogenous Compound];small interfering RNA;spermidine/ec [Endogenous Compound];spermine derivative;spermine n1 acetyltransferase/ec [Endogenous Compound];thialysine acetyltransferase/ec [Endogenous Compound];trientine/pd [Pharmacology];unclassified drug","Hyvonen, M. T.;Weisell, J.;Khomutov, A. R.;Alhonen, L.;Vepsalainen, J.;Keinanen, T. A.",2013,January,http://dx.doi.org/10.1124/dmd.112.047274,0,0,
1481,"Urinary excretion of copper, zinc and iron with and without D-penicillamine administration in relation to hepatic copper concentration in dogs","Hereditary copper-associated hepatitis in dogs resembles Wilson's disease, a copper storage disease in humans. Values for urinary copper excretion are well established in the diagnostic protocol of Wilson's disease, whereas in dogs these have not been evaluated. The objectives of this study were to characterize both basal and D-penicillamine induced urinary copper, zinc and iron excretion in dogs in relation to hepatic copper concentration. Beagles, Beagle-Bedlington terrier cross-breeds homozygous for the COMMD1 gene mutation that causes copper toxicosis, and Labrador retrievers with normal or increased hepatic copper concentrations were investigated. The hepatic copper phenotype was determined by histological evaluation of liver biopsies and measurement of the hepatic copper concentration by instrumental neutron activation analysis. Urinary excretion of copper, iron and zinc was measured via inductively coupled plasma optical emission spectrometry under basal conditions and after oral administration of a single dose (20. mg/kg bodyweight) of the chelator D-penicillamine. There was a rapid increase in urinary excretion of copper and zinc, but not iron after D-penicillamine administration. This increase was not different between dogs with high or normal hepatic copper concentrations. D-penicillamine-induced urinary copper excretion and the copper/creatinine ratio did not correlate with hepatic copper concentrations in the dogs studied, although basal urinary copper/zinc ratios did correlate with hepatic copper concentrations in Labrador retrievers. The latter parameter may be useful in diagnostic and follow-up protocols for copper-associated hepatitis in Labrador retrievers. © 2013 Elsevier Ltd.",Canine;Copper;Hepatitis;Urine;Wilson's disease;aged;animal experiment;animal tissue;article;breed difference;controlled study;copper metabolism;dog;iron metabolism;liver biopsy;liver level;mass spectrometry;neutron activation analysis;nonhuman;phenotype;urinary excretion;urine level;zinc metabolism;iron;zinc,"Fieten, H.;Hugen, S.;van den Ingh, T. S. G. A. M.;Hendriks, W. H.;Vernooij, J. C. M.;Bode, P.;Watson, A. L.;Leegwater, P. A. J.;Rothuizen, J.",2013,August,http://dx.doi.org/10.1016/j.tvjl.2013.03.003,0,0,
1482,Bilateral pallidal stimulation for Wilson's disease,"Background: To report on the clinical efficacy of bilateral globus pallidus internus deep brain stimulation in a 29-year-old patient with severe generalized dystonia secondary to Wilson's disease. Methods: The primary outcome measure was the Burke-Fahn-Marsden Dystonia Scale motor severity score (blinded assessment) and the secondary outcome measures were the Abnormal Involuntary Movement Scale (blinded assessment) and the Zaritt Caregiver Burden Interview score, at 20-week postoperative follow up. Results: There was a 14% improvement in the Burke-Fahn-Marsden Dystonia Scale motor severity score. Abnormal Involuntary Movement Scale score remained unchanged while the Zaritt Caregiver Burden Interview score improved by 44.4%. Conclusions: Bilateral globus pallidus deep brain stimulation can be effective in ameliorating dystonia and caregiver burden in Wilson's disease. Outcomes may depend on the stage of the disease at which the surgical procedure is completed. © 2013 Movement Disorder Society.",Deep brain stimulation;Globus pallidus;Wilson's disease;Abnormal Involuntary Movement Scale;adult;article;biopsy;brain depth stimulation;brain size;brain stem;burke fahn marsden dystonia scale;caregiver burden;case report;ceruloplasmin blood level;daily life activity;disease severity;dysarthria;dysphagia;dystonia;feeding apparatus;follow up;gait disorder;generalized dystonia;human;human tissue;implantable pulse generator;involuntary movement;limb movement;liver fibrosis;male;microelectrode;nuclear magnetic resonance imaging;outcome assessment;posterior fossa;postoperative period;priority journal;slit lamp;tremor;wheelchair;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];Zaritt Caregiver Burden Interview score;botulinum toxin A/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;gabapentin/dt [Drug Therapy];lorazepam/dt [Drug Therapy];lorazepam/li [Sublingual Drug Administration];trazodone/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Sidiropoulos, C.;Hutchison, W.;Mestre, T.;Moro, E.;Prescott, I. A.;Mizrachi, A. V.;Fallis, M.;Rughani, A. I.;Kalia, S. K.;Lozano, A.;Fox, S.",2013,August,http://dx.doi.org/10.1002/mds.25446,0,0,
1483,Susceptibility weighted imaging in the evaluation of movement disorders,"Movement disorders are neurodegenerative disorders associated with abnormalities of brain iron deposition. In this presentation, we aim to describe the role of susceptibility weighted imaging (SWI) in the imaging of patients with movement disorders and differentiate between the various disorders. SWI is a high-resolution, fully velocity-encoded gradient-echo magnetic resonance imaging (MRI) sequence that consists of using both magnitude and phase information. We describe briefly the physics behind this sequence and the post-processing techniques used. The anatomy of the midbrain and basal ganglia in normal subjects on SWI is covered. A number of neurodegenerative disorders are associated with abnormal iron deposition, which can be detected due to the susceptibility effects. © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.",aging;basal ganglion;brain calcification/di [Diagnosis];corticobasal degeneration/di [Diagnosis];dementia/di [Diagnosis];diagnostic accuracy;dystonia/di [Diagnosis];human;hyperkinesia;hypokinesia;idiopathic disease/di [Diagnosis];image analysis;iron overload;lipid peroxidation;magnetic field;mesencephalon;mineralization;motor dysfunction/di [Diagnosis];nerve degeneration;neurodegeneration with brain iron accumulation/di [Diagnosis];Parkinson disease/di [Diagnosis];priority journal;progressive supranuclear palsy/di [Diagnosis];review;Shy Drager syndrome/di [Diagnosis];striopallidodentate calcinosis;substantia nigra;susceptibility weighted imaging;three dimensional imaging;Unified Parkinson Disease Rating Scale;Wilson disease/di [Diagnosis];aluminum/ec [Endogenous Compound];calcium/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemosiderin/ec [Endogenous Compound];iron/ec [Endogenous Compound];lactoferrin/ec [Endogenous Compound];magnesium/ec [Endogenous Compound];magnetite/ec [Endogenous Compound];manganese/ec [Endogenous Compound];oxygen radical/ec [Endogenous Compound];phosphorus/ec [Endogenous Compound];potassium/ec [Endogenous Compound];transferrin/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Hingwala, D. R.;Kesavadas, C.;Thomas, B.;Kapilamoorthy, T. R.",2013,,http://dx.doi.org/10.1016/j.crad.2012.12.003,0,0,
1484,The adverse health consequences of the use of multiple performance- enhancing substances-a deadly cocktail,"Context: The harmful consequences of abuse of performance-enhancing substances (PESs), stimulants, and masking agents among athletes, recreational weight lifters, and physical trainers are common. However, the adverse health outcomes with severe unexpected and dramatic consequences are unrecognized or under-reported at the expense of short-term glory or body-image effects, especially in elite sports. Objective:Wereport the case of a recreational weight lifter/physical trainer to help summarize the adverse health consequences and outcomes of polypharmacy among athletes and growing subsets in our populationengagedin physical/fitness training.Weshowthat in addition to the risk inherent to ""stacking"" of PESs, the users are predisposed to harmful consequences, including risk of exposure to toxic contaminants. Design and Setting: A previously healthy man with chronic use of multiple PESs, stimulants, and masking agents presented to a tertiary-care hospital with jaundice and mild hepatitis with rapid progression into liver and multisystem organ failure. This is followed by a brief overview of the specific toxicity (arsenic) and PESs that contributed to the poor outcome in this case. Conclusion: Surreptitiously or self-administered cocktails of potential PESs including anabolic agents, emerging classes of GH-releasing peptides, androgen precursors, stimulants, and masking agents could lead to adverse consequences including early mortality, multisystem pathology, unmask/accelerate malignancy, and expose or predispose users to extreme danger from contaminants. This cautionary case reinforces the need to increase awareness and highlights the challenges that testing agencies, regulators, and clinicians face in the fast-developing licit/illicit trade of these products. © 2013 by The Endocrine Society.",abdominal cramp;acne;adult;alanine aminotransferase blood level;alkaline phosphatase blood level;arsenic poisoning/di [Diagnosis];arsenic poisoning/dt [Drug Therapy];article;aspartate aminotransferase blood level;athletic trainer;bilirubin blood level;blood clotting disorder/di [Diagnosis];bone marrow depression;brain disease;case report;cause of death;clinical feature;creatinine blood level;deterioration;diarrhea;disease course;drug use;fluid resuscitation;gamma glutamyl transferase blood level;headache;hemodialysis;hepatitis/di [Diagnosis];hepatomegaly;human;hydrocortisone blood level;jaundice;kidney failure/di [Diagnosis];kidney failure/th [Therapy];liver dysfunction/di [Diagnosis];male;myalgia;nausea;neutropenia;pancytopenia/di [Diagnosis];physical trainer;polycythemia/di [Diagnosis];polyneuropathy;priority journal;protein blood level;pruritus;substance abuse;testis atrophy;thrombocytopenia;thyroxine blood level;treatment failure;triacylglycerol lipase blood level;urea blood level;vomiting;Wilson disease/di [Diagnosis];young adult;alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];amiloride;anabolic agent/to [Drug Toxicity];ascorbic acid;aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];C reactive protein/ec [Endogenous Compound];chorionic gonadotropin;clenbuterol;gamma glutamyltransferase/ec [Endogenous Compound];glutamine;human growth hormone;hydrochlorothiazide;hydrocortisone/ec [Endogenous Compound];leucine;nandrolone decanoate/to [Drug Toxicity];performance enhancing substance/to [Drug Toxicity];prolactin/ec [Endogenous Compound];propionic acid/to [Drug Toxicity];somatomedin C;succimer di sec butyl ester/dt [Drug Therapy];tamoxifen;testosterone enantate/to [Drug Toxicity];thyrotropin/ec [Endogenous Compound];thyroxine/ec [Endogenous Compound];triacylglycerol lipase/ec [Endogenous Compound];unindexed drug;urea/ec [Endogenous Compound];zinc,"Perera, N. J.;Steinbeck, K. S.;Shackel, N.",2013,December,http://dx.doi.org/10.1210/jc.2013-2310,0,0,
1485,Wilson's disease: Update on integrated Chinese and western medicine,"Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism caused by ATP7B gene mutation. As WD is an inherited disease of the nervous system that is not curable; early diagnosis with early and life-long treatment leads to better prognoses. Currently, the recommended treatment for WD is integrated Chinese and Western medicine. A number of studies indicate that treatment of integrative medicine can not only enforce the de-copper effect but also improve liver function, intelligence, and other factors. This article reviewed in detail the advantages of WD treated with Chinese and Western medicine together. © The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2012.",Chinese medicine;Gandou Decoction;Integrated medicine;Wilson's disease;acupuncture;acute liver failure/si [Side Effect];anaphylaxis/si [Side Effect];article;autoimmune disease/si [Side Effect];disease severity;drug cost;drug formulation;drug hypersensitivity/si [Side Effect];drug mechanism;drug safety;follow up;gastrointestinal symptom/si [Side Effect];gene therapy;hemodialysis;hemolytic anemia/si [Side Effect];hepatocyte transplantation;human;integrative medicine;intestine absorption;leukopenia/si [Side Effect];liver transplantation;maintenance therapy;nonhuman;priority journal;stem cell transplantation;thrombocytopenia/si [Side Effect];traditional medicine;treatment duration;unspecified side effect/si [Side Effect];Westem medicine;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alismatis rhizoma extract/dt [Drug Therapy];alismatis rhizoma extract/pd [Pharmacology];bushen jianpi decoction/pd [Pharmacology];chaihuang gandou powder/dt [Drug Therapy];chelating agent/dt [Drug Therapy];Chinese drug/dt [Drug Therapy];Chinese drug/pd [Pharmacology];copper;copper chelating agent/dt [Drug Therapy];Coptis rhizome extract/dt [Drug Therapy];Coptis rhizome extract/pd [Pharmacology];Curcumae longae rhizoma extract/dt [Drug Therapy];Curcumae longae rhizoma extract/pd [Pharmacology];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/dt [Drug Therapy];edetate calcium disodium/ae [Adverse Drug Reaction];edetate calcium disodium/dt [Drug Therapy];edetate calcium disodium/im [Intramuscular Drug Administration];edetate calcium disodium/iv [Intravenous Drug Administration];gandou decoction/dt [Drug Therapy];gandou decoction/pd [Pharmacology];gluconate zinc/ae [Adverse Drug Reaction];gluconate zinc/po [Oral Drug Administration];gluconate zinc/pd [Pharmacology];licorzinc/ae [Adverse Drug Reaction];licorzinc/pd [Pharmacology];Lysimachiae extract/dt [Drug Therapy];Lysimachiae extract/pd [Pharmacology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];rhubarb extract/dt [Drug Therapy];rhubarb extract/pd [Pharmacology];shugan lidan paidu decoction/dt [Drug Therapy];shugan lidan paidu decoction/pr [Pharmaceutics];shugan lidan paidu decoction/pd [Pharmacology];sodium dimercaptosulphonate/ae [Adverse Drug Reaction];sodium dimercaptosulphonate/dt [Drug Therapy];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];trientine/dt [Drug Therapy];trientine/pe [Pharmacoeconomics];trientine/pd [Pharmacology];unclassified drug;xiaoyao powder/dt [Drug Therapy];zinc acetate/pd [Pharmacology];zinc derivative/pd [Pharmacology];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/po [Oral Drug Administration];zinc sulfate/pd [Pharmacology],"Li, W. J.;Wang, J. F.;Wang, X. P.",2013,March,http://dx.doi.org/10.1007/S11655-012-1089-8,0,0,
1486,Acute onset anarthria without hepatic manifestation: A rare presentation of Wilson disease,"Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. Acute onset anarthria as the heralding and predominant presenting feature has been rarely reported in the literature. We reported a case of a 12-year-old girl who presented with acute onset anarthria and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was made. The patient showed partial improvement after she was started on copper chelating agents and anticholinergics.",anarthria/co [Complication];anarthria/di [Diagnosis];article;basal ganglion;brain radiography;case report;child;clinical feature;cornea disease/di [Diagnosis];diet therapy;disease duration;dystonia/co [Complication];dystonia/di [Diagnosis];eye examination;female;human;kayser fleischer ring;nuclear magnetic resonance imaging;priority journal;school child;thalamus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Verma, R.;Bhandari, A.;Tiwari, N.;Chaudhari, T. S.",2013,20 Aug,http://dx.doi.org/10.1136/bcr-2013-010415,0,0,
1487,Spasmodic muscle cramps and weakness as presenting symptoms in wilson disease,"Wilson disease (WD) is an autosomal-recessive disorder of hepatic copper metabolism that has tremendous variability in its presentation. Phenotypic diversity of the disease can lead to delayed diagnosis. We describe a case of WD in a 10-year-old boy presenting with 3 months of increasingly intense, spasmodic lower extremity muscle cramps. Physical examination revealed tenderness on calf palpation and dark flat lesions over his ankles, knees, and elbows. Initial testing revealed creatine kinase of 302 IU/L (normal 24-248 IU/L), hemoglobin of 8.9 g/dL (11.5-15.5 g/dL), aspartate aminotransferase of 114 IU/L (16-52 IU/L), alanine aminotransferase of 54 IU/L (2-30 IU/L), and myoglobinuria. Extensive evaluation of his myopathy, including MRI and muscle biopsy, was negative. Additional laboratory tests revealed a prothrombin time of 21.3 seconds (11.8-15.5 seconds), total bilirubin of 1.4 mg/dL (<1 mg/dL), direct bilirubin of 0.5 mg/dL (<0.3 mg/dL), albumin of 2.1 g/dL (3.1-4.6 g/dL), a reticulocyte percentage of 4.5% (0.5%-2.5%), a negative Coombs direct antibody test, ceruloplasmin of 3 mg/dL (21-51 mg/dL), and 24-h urine copper of 393 mug/24 h (15-60 mug/24 h). Liver biopsy showed patchy advanced fibrosis, mild inflammation, positive staining for copper, and a tissue copper concentration of 768 mug/g (10-35 mug/g). Brain MRI revealed symmetric intrinsic T1 shortening within bilateral basal ganglia. Trientene therapy was initiated for WD. Symptoms and laboratory abnormalities resolved and remain normal at 21 months' follow-up. Musculoskeletal involvement in WD is uncommon and typically defined as bone demineralization, arthropathy, or hypokalemic muscle weakness. In patients with unexplained musculoskeletal symptoms and hepatic abnormalities, a diagnosis of WD should be considered and appropriate evaluation initiated. © 2013 by the American Academy of Pediatrics.",Liver disease;Metabolic diseases/disorders;Musculoskeletal pain;Rhabdomyolysis;alanine aminotransferase blood level;albumin blood level;ankle injury;arthropathy;article;aspartate aminotransferase blood level;basal ganglion;bilirubin blood level;bone demineralization;case report;ceruloplasmin blood level;chelation therapy;child;clinical evaluation;clinical feature;copper metabolism;copper tissue level;creatine kinase blood level;delayed diagnosis;disease association;disease duration;elbow injury;follow up;gastrocnemius muscle;hemoglobin blood level;hepatitis/di [Diagnosis];human;human tissue;hypokalemia;knee injury;laboratory test;leg cramp;liver biopsy;liver fibrosis/di [Diagnosis];liver level;male;muscle biopsy;muscle contraction;muscle cramp/di [Diagnosis];muscle disease;musculoskeletal disease;myoglobinuria;myopathy/di [Diagnosis];nuclear magnetic resonance imaging;palpation;phenotypic variation;physical examination;priority journal;prothrombin time;reticulocyte count;school child;tissue level;treatment outcome;urine level;weakness/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper;creatine kinase/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];trientine/dt [Drug Therapy],"Rosen, J. M.;Kuntz, N.;Melin-Aldana, H.;Bass, L. M.",2013,October,http://dx.doi.org/10.1542/peds.2012-2923,0,0,
1488,Wilson disease with situs inversus totalis,"Situs inversus is a positional anomaly that rotates the abdominal internal visceria and when it is associated with transposition of the thoracic organs it is called situs inversus totalis. Wilson disease (or hepatolenticular degeneration) is an autosomal recessive hereditary disease of human copper metabolism, which causes hepatic and neuropsychiatric symptoms. We describe a case report of situs inversus totalis with Wilson disease, which is the first case to our knowledge.",Dextrocardia;Kayser-Fleischer ring;Situs inversus;Wilson disease;abdominal distension;abnormal laboratory result;adult;alanine aminotransferase blood level;albumin blood level;alkaline phosphatase blood level;article;ascites;aspartate aminotransferase blood level;bilirubin blood level;case report;clinical feature;computer assisted tomography;copper blood level;esophagogastroduodenoscopy;human;hypotension;jaundice;liver disease;liver function test;malaise;male;situs inversus/dt [Drug Therapy];situs inversus/di [Diagnosis];treatment outcome;Wilson disease/cn [Congenital Disorder];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Erdogmus, M.;Karahan, S.;Basak, M.;Bulut, K.;Avci, D.;Cetinkaya, A.",2013,,,0,0,
1489,"Neurological Wilson's disease lethal for the son, asymptomatic in the father",,akinesia;athetosis;cachexia;case report;communication disorder;coordination disorder;copper metabolism;dysarthria;dysphagia;dystonia;gait disorder;heart failure;heterozygote;human;letter;liver biopsy;male;nuclear magnetic resonance imaging;priority journal;weight reduction;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Denoyer, Y.;Woimant, F.;Bost, M.;Edan, G.;Drapier, S.",2013,March,http://dx.doi.org/10.1002/mds.25290,0,0,
1490,Angiographic embolization of large duodenal varix in a cirrhotic patient,,adult;angiography;article;artificial embolism;bleeding;case report;disease duration;duodenum disease/th [Therapy];duodenum varicosis/th [Therapy];esophagus varices;female;gastrointestinal endoscopy;human;iron deficiency anemia;liver cirrhosis;melena;portal hypertension/th [Therapy];priority journal;treatment refusal;varicosis;Wilson disease;penicillamine;zinc,"Baran, B.;Soyer, O. M.;Poyanli, A.;Karaca, C.",2013,May,http://dx.doi.org/10.1016/j.dld.2012.10.001,0,0,
1491,Ataxia-telangiectasia or neurologic Wilson's disease: When strong family history becomes a diagnostic bias,,ataxia/si [Side Effect];ataxia telangiectasia;case report;ceruloplasmin blood level;child;drug withdrawal;human;letter;male;muscle rigidity/si [Side Effect];preschool child;substitution therapy;Wilson disease;alpha fetoprotein/ec [Endogenous Compound];copper/ec [Endogenous Compound];immunoglobulin/iv [Intravenous Drug Administration];penicillamine/ae [Adverse Drug Reaction],"Motamed, F.;Benabbas, R.;Ashrafi, M. R.;Aghamohammadi, A.;Rezaei, N.",2013,June,http://dx.doi.org/10.1007/s13760-012-0117-y,0,0,
1492,Novel Bioimaging Techniques of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry for Diagnosis Of Fibrotic and Cirrhotic Liver Disorders,"Background and Aims: Hereditary disorders associated with metal overload or unwanted toxic accumulation of heavy metals can lead to morbidity and mortality. Patients with hereditary hemochromatosis or Wilson disease for example may develop severe hepatic pathology including fibrosis, cirrhosis or hepatocellular carcinoma. While relevant disease genes are identified and genetic testing is applicable, liver biopsy in combination with metal detecting techniques such as energy-dispersive X-ray spectroscopy (EDX) is still applied for accurate diagnosis of metals. Vice versa, several metals are needed in trace amounts for carrying out vital functions and their deficiency due to rapid growth, pregnancy, excessive blood loss, and insufficient nutritional or digestive uptake results in organic and systemic shortcomings. Established in situ techniques, such as EDX-ray spectroscopy, are not sensitive enough to analyze trace metal distribution and the quantification of metal images is difficult. Methods: In this study, we developed a quantitative biometal imaging technique of human liver tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in order to compare the distribution of selected metals in cryo-sections of healthy and fibrotic/cirrhotic livers. Results: Most of the metals are homogeneous distributed within the normal tissue, while they are redirected within fibrotic livers resulting in significant metal deposits. Moreover, total iron and copper concentrations in diseased liver were found about 3-5 times higher than in normal liver samples. Conclusions: Biometal imaging via LA-ICP-MS is a sensitive innovative diagnostic tool that will impact clinical practice in identification and evaluation of hepatic metal disorders and to detect subtle metal variations during ongoing hepatic fibrogenesis. © 2013 M-M et al.",article;concentration (parameters);controlled study;human;human tissue;immunohistochemistry;in vitro study;laser surgery;liver cirrhosis;liver fibrosis;mass spectrometry;metal metabolism;process optimization;quantitative analysis;reproducibility;scanning electron microscopy;tissue distribution;cadmium;calcium;cobalt;copper;iron;magnesium;manganese;mercury;metal;molybdenum;phosphorus;potassium;silver;sodium;tin;zinc,"M-M, P.;Weiskirchen, R.;Gassler, N.;Bosserhoff, A. K.;Becker, J. S.",2013,07 Mar,http://dx.doi.org/10.1371/journal.pone.0058702,0,0,
1493,Selective slowing of downward saccades in Wilson's disease,,mri;Saccades;Smooth pursuit;Wilson's disease;abnormal laboratory result;adult;ATP7B gene;case report;clinical feature;copper blood level;dysarthria;dysphagia;eye movement disorder/di [Diagnosis];follow up;gene;gene mutation;human;letter;male;nuclear magnetic resonance imaging;physical examination;priority journal;protein blood level;saccadic eye movement;treatment outcome;urine level;Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Jung, H. K.;Choi, S. Y.;Kim, J. M.;Kim, J. S.",2013,January,http://dx.doi.org/10.1016/j.parkreldis.2012.05.023,0,0,
1494,ATP7B analysis of a Wilson disease family. [Japanese],"Wilson disease is a genetic copper toxicosis due to hepatic copper transporter ATP7B deficiency. The primary lesion is copper-induced liver damage that progresses to cirrhosis, and may be complicated by extrahepatic lesions. Compound heterozygous mutations were identified in the ATP7B of a 16-year-old male patient with neurological Wilson disease. A family study disclosed different mutations in the parents, compound heterozygous mutations from the parents in the 12-year-old sister, and a maternal mutation in the 14-year-old sister. According to the autosomal recessive inheritance of this disease, the family members with compound heterozygous mutations are affected, but those with a heterozygous mutation are not affected by copper toxicosis. Both the proband and an asymptomatic sister with the disease trait were effectively treated with penicillamine and vitamin B<inf>6</inf>. ATP7B analysis, recently authorized in Japan, provides a noninvasive, definitive diagnosis of Wilson disease. © 2013 The Japan Society of Hepatology.",ATP7B analysis;Ceruloplasmin;Genetic disorders of copper metabolism;Wilson disease;adolescent;article;autosomal recessive inheritance;case report;human;intoxication;liver cirrhosis;liver injury;male;mutation;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Tatsumi, Y.;Miura, Y.;Hattori, A.;Hayashi, H.;Kato, K.;Ueyama, J.;Wakusawa, S.;Hayashi, K.;Katano, Y.;Goto, H.",2013,30 May,http://dx.doi.org/10.2957/kanzo.54.334,0,0,
1495,Pathological fractures as an initial presentation of Wilson's disease,"Wilson's disease (WD) has varied phenotypic presentations. Here we report the case of a 16-year-old boy who presented with a history of multiple pathological fractures, severe joint deformities, hepatic dysfunction, cognitive decline and limb dystonia. On examination, the patient had pinched out facies, pallor and leukonychia totalis. Bilateral Kayser Fleischer (KF) ring was present. Musculoskeletal examination revealed pectus carinatum, bilateral genu valgus and gun-stock deformity of the left elbow joint. Splenomegaly and moderate ascites were present. Neurological examination revealed mild rigidity and intermittent episodes of dystonic posturing of all four limbs. On this basis a diagnosis of WD with dystonia with cirrhosis of liver with portal hypertension with renal tubular acidosis with renal rickets was thought likely. Investigations confirmed the diagnosis. The patient was started on treatment but he did not improve. He suffered aspiration pneumonia during his hospital stay and succumbed to the illness. Copyright 2013 BMJ Publishing Group. All rights reserved.",adolescent;arthropathy;article;ascites;aspiration pneumonia/co [Complication];blood examination;case report;clinical feature;cognitive defect;disease severity;dystonia/dt [Drug Therapy];echography;hospitalization;human;kidney tubule acidosis/dt [Drug Therapy];liver cirrhosis;liver dysfunction;male;muscle rigidity;nuclear magnetic resonance imaging;pathologic fracture;portal hypertension/dt [Drug Therapy];priority journal;splenomegaly;treatment failure;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];bicarbonate/dt [Drug Therapy];bicarbonate/po [Oral Drug Administration];calcium/dt [Drug Therapy];colecalciferol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];propranolol/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc/dt [Drug Therapy],"Verma, R.;Junewar, V.;Sahu, R.",2013,,http://dx.doi.org/10.1136/bcr-2013-008857,0,0,
1496,Copper phenotype in Alzheimer's disease: Dissecting the pathway,"Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. Unfortunately, none of these seems to clarify the complexity of the pathogenesis. In fact, diverse and inde-pendent pathogenetic pathways can be disrupted at the same time, and each contributes to disease etiology. In recent years, researchers have begun studying biometals more deeply. A number of studies have shown that metal dyshomeostasis may enhance AD onset and pro-gression. Specifically, different authors have hypothesized that alterations in metal metabolism are associated with an increased in met-al- related oxidative stress and beta-amyloid oligomer formation and precipitation. Studies conducted in vivo, in vitro, in living patients and in silico studies have demonstrated that local and systemic defects in copper metabolism are characteristic signs of AD. This strongly supports the hypothesis that copper pathways may be disrupted by the disease. More specifically, a copper phenotype can be proposed for AD, based on defects found in genes involved in copper metabolism. In this review, we describe copper dyshomeostasis in AD patients and attempt to explain the basis of the AD copper phenotype. Dissecting copper pathways, we highlight mechanisms which may be at the basis of the disease. We also discuss various associated translation outcomes. Copyright © 2013 E-Century Publishing Corporation. All rights reserved.",Alzheimer's disease;Copper;Diagnosis;Drugs;Etiology;Metals;Neurodegeneration;Pathogenesis;Systems biology;Wilson's dis-ease;Alzheimer disease/et [Etiology];clinical trial (topic);copper metabolism;cytochrome c oxidase deficiency;homeostasis;human;immune system;Menkes syndrome;meta analysis (topic);nerve degeneration;oxidative stress;phenotype;review;Wilson disease/dt [Drug Therapy];albumin/ec [Endogenous Compound];alpha 2 macroglobulin/ec [Endogenous Compound];amyloid beta protein/ec [Endogenous Compound];apolipoprotein E/ec [Endogenous Compound];caspase/ec [Endogenous Compound];CD2 associated protein/ec [Endogenous Compound];CD33 antigen/ec [Endogenous Compound];ceruloplasmin;COMM domain containing protein 1/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];cyclooxygenase 17/ec [Endogenous Compound];ephrin receptor A1/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];peroxiredoxin 3/ec [Endogenous Compound];protein/ec [Endogenous Compound];tetrathiomolybdate ammonium/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound],"Squitti, R.;Polimanti, R.",2013,01 Jul,,0,0,
1497,Management of jaundice beyond early infancy,,alpha 1 antitrypsin deficiency/di [Diagnosis];autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];bilirubin blood level;clinical evaluation;clinical feature;cystic fibrosis/di [Diagnosis];cystic fibrosis/dt [Drug Therapy];diet;Epstein Barr virus infection;hepatitis A/di [Diagnosis];hepatitis B/di [Diagnosis];hepatitis B/dt [Drug Therapy];histopathology;human;hyperbilirubinemia;infancy;jaundice;liver biopsy;liver failure/su [Surgery];liver function test;liver transplantation;pathophysiology;review;serology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alpha 1 antitrypsin/ec [Endogenous Compound];autoantibody/ec [Endogenous Compound];azathioprine/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];immunosuppressive agent;lamivudine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy],"Devarajan, K.;Noble-Jamieson, G.",2013,December,http://dx.doi.org/10.1016/j.paed.2013.08.004,0,0,
1498,Neurochemical and behavioral characteristics of toxic milk mice: An animal model of wilson's disease,"Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype of the toxic milk mice is similar to clinical findings in humans suffering from Wilson's disease (WND). In the present study, neurotransmitter system and locomotor performance in toxic milk mice was examined to verify the feasibility of this animal model for studying neuropathology of WND. Mice aged 2 and 12 months were used in the experiment. The mice were tested according to rotarod and footprint protocols. Monoamine content in brain structures was measured by high performance liquid chromatography. In order to detect neuronal loss, expression of enzymes specific for dopaminergic [tyrosine hydroxylase (TH)], noradrenergic (dopamine beta-hydroxylase) and serotoninergic [tryptophan hydroxylase (TPH)] neurons was analyzed by Western blot. The 12-month-old toxic milk mice demonstrated impaired locomotor performance in behavioral tests. Motor deficits were accompanied by increased copper and serotonin content in different brain regions and slight decrease in dopamine concentration in the striatum. The expression of TH, dopamine beta-hydroxylase and TPH in the various brain structures did not differ between toxic milk mice and control animals. Despite differences in brain pathology between humans and rodents, further exploration of neuronal injury in toxic milk mice is warranted to broaden the understanding of neuropathology in WND. © 2013 The Author(s).",Neuropathology;Toxic milk mice;Wilson's disease;aged;animal experiment;animal model;animal tissue;article;body weight;brain level;brain region;ceruloplasmin blood level;controlled study;coordination disorder/et [Etiology];copper brain level;corpus striatum;dopamine brain level;dopaminergic nerve cell;experimental mouse;experimental test;female;gait disorder/et [Etiology];high performance liquid chromatography;iron brain level;liver examination;liver weight;male;motor dysfunction/et [Etiology];mouse;neurochemistry;nonhuman;noradrenergic nerve;priority journal;rotarod test;serotonin brain level;serotoninergic nerve cell;spleen weight;toxic milk mouse;Wilson disease/et [Etiology];zinc brain level;brain monoamine/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;dopamine/ec [Endogenous Compound];dopamine beta monooxygenase/ec [Endogenous Compound];iron;serotonin/ec [Endogenous Compound];tryptophan hydroxylase/ec [Endogenous Compound];tyrosine 3 monooxygenase/ec [Endogenous Compound];zinc,"Przybylkowski, A.;Gromadzka, G.;Wawer, A.;Bulska, E.;Jablonka-Salach, K.;Grygorowicz, T.;Schnejder-Pacholek, A.;Czlonkowski, A.",2013,October,http://dx.doi.org/10.1007/s11064-013-1111-3,0,0,
1499,Monitoring therapy in wilson's disease by the oral radiocopper test. [German],"Background: Wilson's disease is a rare autosomal recessive disorder of hepatic copper transport leading to an inhibition of the biliary excretion of copper. Overloads of the metal mainly in the liver and basal ganglia lead to hepatic but also to extrapyramidal motor as well as psychiatric clinical symptoms. Depending on the stage of the disease, therapy with chelating drugs and zinc is possible but must be given lifelong without longer interruptions. With early diagnosis and consequent treatment, the prognosis of Wilson's disease is excellent and usually the need for liver transplantation can be avoided. Monitoring of treatment is essential because therapy with chelating penicillamine is complicated by side effects, triene is not always available and non-responders to zinc therapy are reported. Method: For the evaluation of the inhibition of enteral resorption of copper in our study an oral radiocopper test was performed in 58 patients with Wilson's disease. Patients were given 10 MBq <sup>64</sup>Cu and radioactivity was measured in serum at one and/or, respectively, 3 h after intake. Altogether 91 tests were evaluated. Results: No inhibition of copper resorption was found in 1 patient under penicillamine therapy. A partial inhibition of enteral resorption could be proved for triene in 6 patients. 48 tests showed a sufficient inhibition with zinc therapy. In 36 tests of the patients taking zinc the inhibition was proved to be not sufficient. In 6 of them it could be improved by increasing the dosage. Triene has been shown to inhibit the resorption of copper as well by this test. No inhibition is seen with penicillamine. Conclusion: The high prevalence of insufficient effectiveness of zinc therapy requires a continuous control. The radiocopper test allows an estimation of the influence of zinc on copper resorption in Wilsons disease. Further studies have to be performed to evaluate the utility of this test. © Georg Thieme Verlag KG Stuttgart . New York.",oral radiocopper test;penicillamine;triene;Wilsons's disease;zinc;article;copper blood level;human;major clinical study;patient monitoring;prognosis;radioactivity;Wilson disease/dt [Drug Therapy];copper 64/cr [Drug Concentration];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Gunther, P.;Kuhn, H. J.;Hermann, W.",2013,,http://dx.doi.org/10.1055/s-0033-1334900,0,0,
1500,Movement disorders: Indian scenario: A clinico-genetic review,"Movement disorder (MD) is an important branch of neurology and has great potentiality in management because of improved diagnosis and therapeutic strategies. Over the last three decades, emphasis has been laid on the evaluation of various MDs in India by a limited number of interested neurologists and basic scientists. In this review, we want to highlight common problems of MDs in India with regard to epidemiology, clinical features and genetics.",Dystonia;epidemiology;essential tremor;genetics;huntington disease;neurodegeneration with brain iron accumulation;Parkinson's disease;Wilson's disease;ceruloplasmin blood level;chorea;demography;follow up;human;Huntington chorea;India;Japanese encephalitis;mortality;motor dysfunction/di [Diagnosis];motor dysfunction/ep [Epidemiology];myoclonus;nuclear magnetic resonance imaging;Parkinson disease;prevalence;pyramidal sign;quality of life;review;risk factor;systematic review;virus encephalitis;Wilson disease;alpha synuclein;gabapentin;leucine rich repeat kinase 2;parkin;penicillamine;sepiapterin reductase;tyrosine 3 monooxygenase;zinc sulfate,"Das, S.;Ghosh, B.;Das, G.;Biswas, A.;Ray, J.",2013,September-October,http://dx.doi.org/10.4103/0028-3886.121908,0,0,
1501,Long-term nutrition assessment in children with Wilson's disease. [Chinese],"Objective: To investigate the long-term nutrition status of children with Wilson's disease treated by different methods. Methods: Fifteen children with Wilson's disease were followed up for anthropometric measurements (height and body weight), blood biochemical parameters detection (blood routine, liver function, blood calcium and blood phosphorus) and bone density determination. Children were divided into penicillamine group and penicillamine+zinc sulfate group based on the therapies, and comparisons were made between two groups. Results: Among the 15 children, 1 had growth retardation, and the other 1 had midrange malnutrition. There was no significant difference in weight for age percentile and Z-score (WAZ), height for age percentile and Z-score (HAZ), and body mass index (BMI) percentile and Z-score (BMIZ) between two groups (P>0.05). There were 3 children with mild anaemia in penicillamine group, and there was 1 child with mild anaemia in penicillamine+zinc sulfate group. The values of alkaline phosphatase in children in penicillamine group were higher than the normal value except for two children. The blood calcium was elevated in 1 child in penicillamine group. The Z-scores of bone density of middle tibia and distal radius were -3 and -3.5 respectively in 1 child in penicillamine group, which were lower than the normal values. There was no significant difference in hemoglobin, total protein, albumin, blood calcium, blood phosphorus, alkaline phosphatase and ratio of bone density of middle tibia to that of distal radius between two groups (P>0.05). Conclusion: Children with Wilson's disease have normal nutrition status after long-term copper displacement and low-copper diet. Penicillamine treatment and penicillamine combined with zinc sulfate treatment have no significant effect on children's physical development.",Children;Nutrition assessment;Wilson's disease;albumin blood level;alkaline phosphatase blood level;anemia;article;body height;body mass;body weight;bone density;calcium blood level;child nutrition;clinical article;follow up;growth retardation;hemoglobin blood level;human;liver function;long term care;malnutrition;nutritional assessment;nutritional status;phosphate blood level;radius;tibia;Wilson disease/dt [Drug Therapy];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];calcium/ec [Endogenous Compound];copper;hemoglobin/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];phosphate/ec [Endogenous Compound];protein/ec [Endogenous Compound];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Lu, X. S.;Jiao, X. T.;Zhao, L.;Liu, X. Q.;Chen, S.;Yang, J. P.",2013,September,http://dx.doi.org/10.3969/j.issn.1674-8115.2013.09.018,0,0,
1502,Wilson's disease,"Wilson s disease (WD) is a genetically determined, autosomal recessive disorder of copper metabolism. The gene ATP<inf>7</inf>B encodes a copper carrier that both transports copper from hepatocyte to bile and ceruloplasmin copper incorporation. WD may present with almost any variety of liver disease at an age ranging from 4-12 years, or with neurological and psychiatric symptoms in adolescence. Less commonly, haemolysis and/or fulminant hepatic failure may be an initial presentation. Low plasma ceruloplasmin, a positive penicillamine challenge test, and a high hepatic copper content suggest the diagnosis. Molecular methods help in diagnosing WD. If diagnosed early, it is treatable with chelators and/or zinc, and has a good prognosis. Fulminant hepatic disease has a poor outcome without transplantation.",Children;Diagnosis;Prognosis;Treatment;Wilson's disease;acute hepatitis;acute liver failure;aminoaciduria;aplastic anemia/si [Side Effect];ascites;ATP7B gene;ceruloplasmin blood level;ceruloplasmin gene;chronic active hepatitis;clinical feature;DNA damage;dose response;drug dose reduction;drug withdrawal;dystonia;enzyme synthesis;Fanconi renotubular syndrome;fever/si [Side Effect];fulminant hepatic failure;gene;gene deletion;glucosuria;hemolysis;hepatosplenomegaly;human;hypercalciuria;incidence;iron deficiency anemia/si [Side Effect];iron metabolism;jaundice;kidney calcification;kidney tubule acidosis/co [Complication];leukocyte count;leukopenia/si [Side Effect];liver cirrhosis;liver disease/dt [Drug Therapy];lymphadenopathy/si [Side Effect];missense mutation;mouth lesion/si [Side Effect];nephrotoxicity/si [Side Effect];nonalcoholic fatty liver;osteoporosis/co [Complication];parkinsonism;pathogenesis;portal hypertension;prevalence;proteinuria/si [Side Effect];rash/si [Side Effect];renal osteodystrophy;review;rickets/co [Complication];skin defect/si [Side Effect];skin disease/si [Side Effect];stomach irritation/si [Side Effect];systemic lupus erythematosus/si [Side Effect];thrombocyte count;thrombocytopenia/si [Side Effect];urinalysis;WD gene;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];pyridoxine;trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Perisic, V. N.",2013,,,0,0,
1503,The acute haemolytic syndrome in Wilson's disease-a review of 22 patients,"An analysis of 321 case notes of patients with Wilson's disease seen between 1955 and 2000 and one case seen in 1949 has revealed that 22 patients presented with a haemolytic crisis. This study was not a specific research project but a retrospective analysis of 321 patients with Wilson's disease seen between 1949 and 2000. All investigations were carried out in the best interests of diagnosis and management of patients referred to my clinic. The delay in diagnosis in 18 cases resulted in progression to severe hepatic disease in 14 cases and to neurological disease in 4 cases. One patient had no symptoms at the time her sister's illness was diagnosed as Wilson's disease. In a second patient, with liver disease, the diagnosis was also made when a sister was found to have Wilson's disease. There was a female to male ratio of 15:7. The average age of onset was 12.6 years and the incidence 6.9%. Delay in diagnosis resulted in nine deaths. Three patients, late in the series, were admitted in the acute phase, two female and one male; of these two responded to chelation therapy, the third required liver transplantation. Haemolysis appeared to be extravascular, and possible mechanisms of the haemolysis are discussed. © The Author 2013.Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved.",adolescent;adult;article;bilirubin blood level;blood clotting factor 7 deficiency;chelation therapy;child;cholecystectomy;copper blood level;disease course;drug substitution;drug withdrawal;erythrocyte count;female;gallstone/su [Surgery];hemoglobin blood level;hemolysis/dt [Drug Therapy];hospital admission;human;incidence;liver disease;liver transplantation;major clinical study;male;neurologic disease;onset age;patient referral;priority journal;prothrombin time;reticulocyte count;retrospective study;school child;sex ratio;Wilson disease/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];bilirubin glucuronide/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];serum albumin/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy],"Walshe, J. M.",2013,November,http://dx.doi.org/10.1093/qjmed/hct137,0,0,
1504,Effect of liver transplantation on brain magnetic resonance imaging pathology in Wilson disease: A case report,"The authors present a case report of a 28-year-old patient with hepatic, but no neurological, signs of Wilson disease, with pathological changes in both the globi pallidi and caudate found with routine brain magnetic resonance imaging (MRI). The patient was recommended for liver transplantation by hepatologists, and during the two years of observation after liver transplantation, MRI brain abnormalities due to Wilson disease completely regressed. On the basis of this case, the authors present an argument for the prognostic significance of brain MRI in Wilson disease as well as current recommendations concerning liver transplantation in Wilson disease.",Copper metabolism;Liver transplantation;Wilson disease;adult;article;blood clotting disorder;case report;echography;follow up;genetic analysis;hepatic artery thrombosis/co [Complication];human;immunosuppressive treatment;laboratory test;liver cirrhosis;male;neurologic examination;nuclear magnetic resonance imaging;ophthalmology;pathology;Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];penicillamine,"Litwin, T.;Dzieyc, K.;Poniatowska, R.;Czlonkowska, A.",2013,,http://dx.doi.org/10.5114/ninp.2013.36763,0,0,
1505,Therapy for systemic metabolic disorders based on the detection of basic corneal landmarks in childhood. [German],"Many systemic lysosomal storage disorders show basic corneal opacities already in childhood. The lysosome is a cell organelle, produced by Golgis apparatus, that is surrounded by a membrane and contains hydrolytic enzymes that break down food molecules, especially proteins and other complex molecules. The ophthalmologists precise diagnosis of corneal clouding at the slit-lamp may reveal the correct interpretation of the specific lysosomal storage disorder. It is very important to diagnose such diseases as soon as possible because today the development of systemic enzymatic therapies has broadened the therapeutic armamentarium for the current standard of care. The following corneal landmarks of systemic storage diseases and of the modern systemic therapy are presented: cornea verticillata in Fabrys disease, periodic infusion of alpha-galactosidase a; Kayser-Fleischers ring in Wilsons disease, zinc, trienetin, low copper diet; multiple, punctiform crystals in cystinosis, cysteamine, Raptor RP 103(DR cysteamine) that reduces the cytotoxity in form of continous dissolving of cystine from lysosome, renal transplantation, haematopoietic stem cell transplantation; peripheral ring, but not true lipid arc, and moderate stromal haze in LCAT-deficiency, injection of recombinant enzyme or of encapsulated LCAT-secreting cells; diffuse stromal haze in mucopolysaccharidoses (MPS). Enzyme replacement therapy is currently indicated for MPS I, MPS II, and MPS VI, haematopoietic stem cell transplantation; painful, bilateral pseudo-dendritic opacities in tyrosinemia type II (eponym: Richner-Hanhart syndrome), low phenylalanine and tyrosine diet result in complete disappearance of corneal alterations with a consecutive painfree period. Strict diet during the whole life is necessary to prevent corneal recurrences and the occurrence of palmo-plantar keratoses. Such therapies can enable the patient to lead an otherwise normal life for decades. © 2013 Georg Thieme Verlag KG Stuttgart . New York.",corneal landmarks;crystals;cystinosis;Fabrys disease;Kayser-Fleischers ring;LCAT deficiency;lysosomal storage disorders;peripheral ring;pseudo-dendritic tyrosinemia II;whorled cornea;Wilsons disease;article;childhood disease/th [Therapy];cornea;cornea opacity;enzyme replacement;Fabry disease;Golgi complex;hematopoietic stem cell transplantation;human;hydrolysis;keratosis;lysosome storage disease;metabolic disorder;mucopolysaccharidosis/th [Therapy];Wilson disease;copper;unclassified drug;zinc;zinc trienetin,"Lisch, W.;Pitz, S.;Geerling, G.",2013,,http://dx.doi.org/10.1055/s-0032-1328524,0,0,
1506,D-penicillamine treatment of copper-associated hepatitis in Labrador retrievers,"d-penicillamine is effectively used in the lifelong treatment of copper toxicosis in Bedlington terriers and Wilson's disease in humans. A complex form of copper-associated hepatitis has recently been characterized in the Labrador retriever. The aims of this study were to evaluate the effectiveness of d-penicillamine treatment for copper-associated hepatitis in this breed, to study the effects on hepatic copper, iron and zinc concentrations, and to evaluate parameters to predict optimal duration of treatment. Forty-three client owned Labrador retrievers that were diagnosed with increased hepatic copper were treated with d-penicillamine and underwent at least one follow-up examination including a liver biopsy for histopathological scoring of inflammatory lesions. Hepatic copper, iron and zinc concentrations were determined in the initial and follow-up biopsies by instrumental neutron activation analysis. The influence of initial hepatic copper concentration, sex, age, d-penicillamine formulation and the occurrence of side effects were investigated for their influence on hepatic copper concentration after a certain period of treatment by generalized mixed modelling. d-penicillamine proved to be effective in reducing hepatic copper concentration and associated inflammatory lesions. Parameters derived from the model can be used to estimate the necessary duration of d-penicillamine treatment for Labrador retrievers with increased hepatic copper concentration. Continuous, lifelong d-penicillamine treatment is not recommended in this breed, as there may be a risk for hepatic copper and zinc deficiency. © 2012 Elsevier Ltd.",Copper toxicosis;Dog;Iron;Liver;Zinc;alanine aminotransferase blood level;alkaline phosphatase blood level;animal experiment;animal tissue;article;controlled study;drug efficacy;drug mechanism;experimental dog;female;follow up;hepatitis/dt [Drug Therapy];histopathology;liver biopsy;liver level;male;nonhuman;retrospective study;scoring system;treatment duration;alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology],"Fieten, H.;Dirksen, K.;van den Ingh, T. S. G. A. M.;Winter, E. A.;Watson, A. L.;Leegwater, P. A. J.;Rothuizen, J.",2013,June,http://dx.doi.org/10.1016/j.tvjl.2012.12.013,0,0,
1507,Astrocyte functions in the copper homeostasis of the brain,"Copper is an essential element that is required for a variety of important cellular functions. Since not only copper deficiency but also excess of copper can seriously affect cellular functions, the cellular copper metabolism is tightly regulated. In brain, astrocytes appear to play a pivotal role in the copper metabolism. With their strategically important localization between capillary endothelial cells and neuronal structures they are ideally positioned to transport copper from the blood-brain barrier to parenchymal brain cells. Accordingly, astrocytes have the capacity to efficiently take up, store and to export copper. Cultured astrocytes appear to be remarkably resistant against copper-induced toxicity. However, copper exposure can lead to profound alterations in the metabolism of these cells. This article will summarize the current knowledge on the copper metabolism of astrocytes, will describe copper-induced alterations in the glucose and glutathione metabolism of astrocytes and will address the potential role of astrocytes in the copper metabolism of the brain in diseases that have been connected with disturbances in brain copper homeostasis. © 2012 Elsevier Ltd. All rights reserved.",Astroglia;Metallothioneins;Neurodegeneration;Oxidative stress;Toxicity;Transport;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];Alzheimer disease/th [Therapy];amino acid metabolism;amyloid plaque;astrocyte;brain;cell function;cell membrane;cell migration;cognition;copper deficiency;copper metabolism;cytotoxicity;degenerative disease/et [Etiology];energy metabolism;gene mutation;genetic association;glucose metabolism;glutathione metabolism;glycolysis;homeostasis;human;Huntington chorea/dt [Drug Therapy];Huntington chorea/et [Etiology];Huntington chorea/th [Therapy];Huntington disease like syndrome/dt [Drug Therapy];loss of function mutation;Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];Menkes syndrome/th [Therapy];nerve cell culture;nonhuman;Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];Parkinson disease/th [Therapy];pH;prion disease/dt [Drug Therapy];prion disease/th [Therapy];priority journal;protein expression;randomized controlled trial (topic);review;supplementation;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];cadmium;clioquinol/dt [Drug Therapy];copper/dt [Drug Therapy];copper/to [Drug Toxicity];copper/pa [Parenteral Drug Administration];copper exporting adenosine triphosphatase/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];cytochrome c oxidase/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];hydrogen peroxide/ec [Endogenous Compound];ionophore/ct [Clinical Trial];ionophore/dt [Drug Therapy];ionophore/pd [Pharmacology];manganese;Menkes protein/ec [Endogenous Compound];n methyl dextro aspartic acid receptor/ec [Endogenous Compound];natural resistance associated macrophage protein 2/ec [Endogenous Compound];pbt 2/ct [Clinical Trial];pbt 2/dt [Drug Therapy];pbt 2/pd [Pharmacology];penicillamine/dt [Drug Therapy];prion protein/ec [Endogenous Compound];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Scheiber, I. F.;Dringen, R.",2013,April,http://dx.doi.org/10.1016/j.neuint.2012.08.017,0,0,
1508,Perioperative management of Wilson disease for therapeutic abortion: A report,,adult;case report;female;foot edema;hepatosplenomegaly;human;hypertransaminasemia;letter;perioperative period;portal vein;postoperative pain/dt [Drug Therapy];prothrombin time;therapeutic abortion;thrombocytopenia;vein dilatation;Wilson disease/dt [Drug Therapy];fresh frozen plasma;penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];thrombocyte concentrate;tramadol/dt [Drug Therapy];tramadol/iv [Intravenous Drug Administration];zinc sulfate/dt [Drug Therapy],"Bhaskar Rao, P.;Singh, N.;Koshy George, S.",2013,October,,0,0,
1509,Hepatitis E virus infection as a cause of acute hepatic failure in a patient of Wilson's disease,Wilson's disease may present as acute hepatic failure and may be missed as a differential diagnosis if there is no previous or family history. An acute insult like viral hepatitis may trigger Wilson's disease and may even progress to fulminant hepatic failure with grave prognosis. HAV and HEV infection have been shown to cause severe illness in patients with established chronic liver disease. This case suggests that viral infection may play a role in acute decompensation in some patients of Wilson's disease.,Fulminant Wilson's disease;Haemolysis;Hepatitis E;abdominal pain;acute liver failure/di [Diagnosis];acute liver failure/et [Etiology];adult;article;bilirubin blood level;case report;cerebral peduncle;ceruloplasmin blood level;fatigue;flapping tremor;hepatic encephalopathy;hepatitis E/di [Diagnosis];hepatosplenomegaly;human;jaundice;male;nuclear magnetic resonance imaging;sleep pattern;slit lamp;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;hepatitis E antibody/ec [Endogenous Compound];immunoglobulin M/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy],"Kumari, P.;Aggarwal, P.;Dev, N.;Sharma, S. C.",2013,,,0,0,
1510,Wilson's disease - Early detection and treatment improves outome,"Wilson's disease is an autosomal recessive familial disorder due to an inborn error of copper metabolism. It is characterised by multiorgan involvement due to excessive deposition of copper in various organs. After the second decade of life, 75% of the cases present with neurological involvement, and we report such a case who presented with various neurological features and had asymptomatic hepatic involvement.",Hepatic;Hepatolenticular degeneration;Neurological;Wilson's disease (WD);academic failure;achilles reflex;adolescent;article;case report;computer assisted tomography;depression;dyskinesia;follow up;hand tremor;hepatomegaly;human;human tissue;inflammation;liver biopsy;liver fibrosis;male;nuclear magnetic resonance imaging;suicidal ideation;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Katyal, V. K.;Gupta, T.;Goel, R. K.;Mahajan, K.;Agarwal, S.",2013,,,0,0,
1511,"Wilson's disease with neurological presentation, without hepatic involvement in two siblings","Wilson's Disease (WD) is a rare, autosomal, recessive, inborn error of the copper metabolism, which is caused by a mutation in the copper-transporting gene, ATP7B. The presentation is usually neurologic or hepatic, which is seen in 40% of the patients. The diagnosis depends primarily on the clinical features, the biochemical parameters and the presence of the Kayser - Fleischer ring. Here, we are reporting two siblings who were affected by Wilson's disease, with only neurological manifestations, without any hepatic involvement.",atp7b;Dystonia;Kayser - fleischer ring;Wilson's disease;adolescent;adult;article;Babinski reflex;case report;clinical feature;clonus;copper metabolism;diagnostic error;diet restriction;drug treatment failure;dysarthria;dystonia/dt [Drug Therapy];human;liver disease;male;motor dysfunction/dt [Drug Therapy];neurologic disease/di [Diagnosis];neurologic disease/dt [Drug Therapy];neurologic disease/th [Therapy];nuclear magnetic resonance imaging;sibling;tegmentum;tendon reflex;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];anticonvulsive agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];trihexyphenidyl/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration],"Kant Kumar, M.;Kumar, V.;Kumar Singh, P.",2013,,http://dx.doi.org/10.7860/JCDR/2013/5974.3188,0,0,
1512,Treating hypothyroidism,,alternative medicine;disease course;editorial;euthyroid sick syndrome;Hashimoto disease;hormone synthesis;human;hypothyroidism/co [Complication];hypothyroidism/dt [Drug Therapy];iron deficiency;nonhuman;subclinical hypothyroidism;supplementation;thyroid function;thyroid gland;treatment planning;Wilson disease/dt [Drug Therapy];herbaceous agent/cb [Drug Combination];herbaceous agent/dt [Drug Therapy];liothyronine/cb [Drug Combination];liothyronine/dt [Drug Therapy];mineral/cb [Drug Combination];mineral/dt [Drug Therapy];selenium/ct [Clinical Trial];thyrotropin/ec [Endogenous Compound];thyroxine/dt [Drug Therapy];vitamin/cb [Drug Combination];vitamin/dt [Drug Therapy];zinc sulfate,"Prousky, J. E.",2013,,,0,0,
1513,Late occurrence of isolated obsessive-compulsive behavior in a boy with Wilson's disease on treatment,,case report;caudate nucleus;ceruloplasmin blood level;child;dysarthria;dysgraphia;human;jaundice;letter;male;neuroimaging;nuclear magnetic resonance imaging;obsessive compulsive disorder;priority journal;putamen;school child;Wilson disease;ceruloplasmin/ec [Endogenous Compound];copper;penicillamine;pyridoxine;trihexyphenidyl;zinc acetate,"Sahu, J. K.;Singhi, P.;Malhotra, S.",2013,February,http://dx.doi.org/10.1177/0883073812465011,0,0,
1514,Unusual epileptic deterioration and extensive white matter lesion during treatment in Wilson's disease,"Background: Wilson's disease (WD) is a genetic disorder which can be controlled fairly well with decupuration therapy. However, symptoms, on rare occasions, can worsen even when WD is being treated. Herein, we report a case involving unusual neurological deterioration during decupuration therapy for WD.Case presentation: A 28-year-old man was diagnosed with WD 13 years prior to his clinical visit; however, his drug compliance has been poor over the years. He was treated with trientine because tremors and dysarthria have presented in recent years. However, dysarthria and dystonia developed in his limbs, which were worse on the right side and had been aggravated for several weeks despite good drug compliance. His symptoms were fluctuating. It was initially misdiagnosed as dystonia; although, it turned out to be a seizure due to cortical degeneration. These symptoms were completely resolved with antiepileptic drugs. Moreover, the cortical enhancement of bifrontal degeneration has disappeared on the MRI.Conclusion: This case showed unusual epileptic neurologic deterioration due to cortical degeneration during decupuration therapy. Seizures in WD can easily be mistaken as part of dystonia. However, the fluctuating symptoms suggest a seizure. © 2013 Kim et al.; licensee BioMed Central Ltd.",Cortical lesion: MRI;Dystonia;Seizure;Wilson's disease;adult;aggression;article;basal ganglion;behavior change;brain degeneration;brain stem;case report;chronic liver disease;clinical feature;contrast enhancement;diagnostic error;disease exacerbation;drug substitution;drug withdrawal;dysarthria;echography;electroencephalogram;epilepsy;frontal gyrus;gait disorder;general condition deterioration;human;irritability;male;medication compliance;mood disorder;motor dysfunction;neuroimaging;neurologic disease/dt [Drug Therapy];neurologic examination;nuclear magnetic resonance imaging;paresthesia/si [Side Effect];speech disorder;stuttering;superior frontal gyrus;thalamus;tremor;white matter lesion;Wilson disease/dt [Drug Therapy];etiracetam/dt [Drug Therapy];oxcarbazepine/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Kim, Y. E.;Yun, J. Y.;Yang, H. J.;Kim, H. J.;Jeon, B. S.",2013,25 Sep,http://dx.doi.org/10.1186/1471-2377-13-127,0,0,
1515,Metabolic disorders presenting as liver disease,"The liver is a highly metabolically active organ and many inherited metabolic disorders have hepatic manifestations. The clinical presentation in these patients cannot usually be distinguished from liver disease due to acquired causes like infection, drugs or haematological disorders. Manifestations include acute and chronic liver failure, cholestasis and hepatomegaly. Metabolic causes of acute liver failure in childhood can be as high as 35%. Certain disorders like citrin deficiency and Niemann-Pick C disease may present in infancy with self-limiting cholestasis before presenting in later childhood or adulthood with irreversible disease. This article reviews important details from the history and clinical examination when evaluating the paediatric patient with suspected metabolic disease, the specialist and genetic tests when investigating, and also discusses specific disorders, their clinical course and treatment. The role of liver transplantation is also briefly discussed. Increased awareness of this group of disorders is important as in many cases, early diagnosis leads to early intervention with improved outcome. Diagnosis also allows genetic counselling and future family planning. © 2013 Elsevier Ltd.",Acute liver failure;Cholestasis;Chronic liver failure;Hepatomegaly;Inherited;Jaundice;Liver;Metabolic;Transplantation;acute liver failure/su [Surgery];acute liver failure/th [Therapy];aminoacidopathy/th [Therapy];anamnesis;bile acid synthesis;blood analysis;cerebrospinal fluid examination;cerebrotendinous xanthomatosis/di [Diagnosis];cerebrotendinous xanthomatosis/dt [Drug Therapy];cholesterol storage ester disease;citrin deficiency/di [Diagnosis];citrin deficiency/th [Therapy];clinical examination;diagnostic test;diet therapy;disorders of mitochondrial functions/di [Diagnosis];disorders of mitochondrial functions/et [Etiology];enzyme replacement;fatty acid oxidation;fatty acid oxidation defect/di [Diagnosis];fatty acid oxidation defect/th [Therapy];fetus hydrops;galactosemia/di [Diagnosis];galactosemia/et [Etiology];galactosemia/th [Therapy];gene mutation;genetic screening;glycogen storage disease/di [Diagnosis];glycogen storage disease/th [Therapy];hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hepatic encephalopathy;hepatomegaly/th [Therapy];hepatosplenomegaly;hereditary fructose intolerance/di [Diagnosis];hereditary fructose intolerance/th [Therapy];human;hyperammonemia;hypoglycemia;liver disease/di [Diagnosis];liver disease/su [Surgery];liver disease/th [Therapy];liver dysfunction;liver transplantation;medical specialist;metabolic disorder/di [Diagnosis];metabolic disorder/th [Therapy];metabolic liver disease/di [Diagnosis];metabolic liver disease/su [Surgery];metabolic liver disease/th [Therapy];muscle biopsy;muscle hypotonia;neonatal hemochromatosis/dt [Drug Therapy];neonatal hemochromatosis/di [Diagnosis];newborn disease/di [Diagnosis];newborn disease/dt [Drug Therapy];Niemann Pick disease/di [Diagnosis];Niemann Pick disease/dt [Drug Therapy];obstructive jaundice/th [Therapy];progressive familial intrahepatic cholestasis;review;skin biopsy;tyrosinemia/di [Diagnosis];tyrosinemia/dt [Drug Therapy];tyrosinemia/th [Therapy];tyrosinemia type 1/dt [Drug Therapy];tyrosinemia type 1/di [Diagnosis];tyrosinemia type 1/th [Therapy];urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wolman disease;acylcarnitine/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];amino acid/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];antioxidant/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];bile acid/ec [Endogenous Compound];carboxylic acid/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];cholic acid/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];galactose 1 phosphate uridylyltransferase/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];glucose/ec [Endogenous Compound];iron chelating agent/dt [Drug Therapy];lactic acid/ec [Endogenous Compound];miglustat/dt [Drug Therapy];nitisinone/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Pierre, G.;Chronopoulou, E.",2013,December,http://dx.doi.org/10.1016/j.paed.2013.05.016,0,0,
1516,Wilson's disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease,"Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson's disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b), and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum alanine aminotransferase (ALT) and liver tumor necrosis factor alpha (Tnf-alpha) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-alpha and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels. Conclusion: Reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD. © 2012 American Association for the Study of Liver Diseases.",alanine aminotransferase blood level;animal cell;animal experiment;animal model;animal tissue;article;chelation;controlled study;diet supplementation;disease severity;DNA methylation;down regulation;endoplasmic reticulum stress;genetic transcription;hepatitis;histopathology;lipogenesis;mouse;nonhuman;priority journal;protein expression;Wilson disease;adenosylhomocysteinase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];betaine;copper;DNA/ec [Endogenous Compound];DNA methyltransferase 1/ec [Endogenous Compound];DNA methyltransferase 3A/ec [Endogenous Compound];DNA methyltransferase 3B/ec [Endogenous Compound];fatty acid/ec [Endogenous Compound];lipid/ec [Endogenous Compound];methionine/ec [Endogenous Compound];penicillamine;s adenosylhomocysteine/ec [Endogenous Compound];tumor necrosis factor alpha/ec [Endogenous Compound],"Medici, V.;Shibata, N. M.;Kharbanda, K. K.;Lasalle, J. M.;Woods, R.;Liu, S.;Engelberg, J. A.;Devaraj, S.;Torok, N. J.;Jiang, J. X.;Havel, P. J.;Lonnerdal, B.;Kim, K.;Halsted, C. H.",2013,February,http://dx.doi.org/10.1002/hep.26047,0,0,
1517,"Wilson disease, genotype and infertility: Is there a correlation?",,adult;amino acid substitution;autosomal recessive disorder;case report;copper metabolism;gene amplification;gene mutation;gene sequence;genetic counseling;genetic screening;genotype;heterozygote;human;karyotype;letter;male;male infertility;pathophysiology;phenotype;priority journal;semen analysis;spermatozoon abnormality/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];copper/to [Drug Toxicity];copper exporting adenosine triphosphatase/ec [Endogenous Compound];genomic DNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Frikha, R.;Abdelmoula, N. B.;Rebai, T.",2013,August,http://dx.doi.org/10.1007/s12020-012-9872-z,0,0,
1518,Personality changes in a patient with wilson's disease,"Personality changes in a patient with Wilson's disease Wilson's disease (WD) is a rare disorder that primarily affects liver and brain, with the onset frequently in adolescence. Psychiatric symptoms are remarkable and the first manifestation in most cases. WD, when first presented with psychiatric symptoms, delay in the diagnosis can often occurs. This study describes a case of WD starting with tremor and depression and developing permanent personality and behavioral changes later.",Personality change;Psychiatric symptom;Wilson's disease;adult;aggression;article;ataxia/dt [Drug Therapy];attention disturbance/di [Diagnosis];behavior change;borderline state/di [Diagnosis];case report;demoralization;depression/dt [Drug Therapy];disease association;dysphoria/dt [Drug Therapy];Hamilton scale;hand tremor/dt [Drug Therapy];histrionic personality disorder/di [Diagnosis];human;irritability;liver function test;male;masturbation;patient attitude;patient compliance;personality disorder/dt [Drug Therapy];personality disorder/di [Diagnosis];self care;suicide attempt/dt [Drug Therapy];thrombocyte count;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];amisulpride/dt [Drug Therapy];antidepressant agent/dt [Drug Therapy];risperidone/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Genc, E. S.;Genc, A.;Guveneroglu, N. U.",2013,,http://dx.doi.org/10.5350/DAJPN2013260310,0,0,
1519,"Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch between Cortical and Striatal Interneurons","Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB, and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform toward a subtype of GABAergic striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome). © 2013 Elsevier Inc.",animal cell;animal experiment;animal tissue;article;brain nerve cell;cell migration;cell transformation;cMaf gene;controlled study;corpus striatum;CXCR7 gene;dlx1 gene;Dlx2 gene;embryo;epilepsy/et [Etiology];female;gene;gene deletion;gene expression;gene function;gene repression;gene switching;genetic regulation;interneuron;Mafb gene;male;median eminence;mouse;mowat wilson syndrome/et [Etiology];nerve cell differentiation;neurologic disease/et [Etiology];nkx2 1 gene;nonhuman;phenotype;priority journal;sip1 gene;ZEB2 gene;4 aminobutyric acid receptor/ec [Endogenous Compound];chemokine receptor CXCR7;RNA/ec [Endogenous Compound];transcription factor c Maf/ec [Endogenous Compound];transcription factor MafB/ec [Endogenous Compound],"McKinsey, G. L.;Lindtner, S.;Trzcinski, B.;Visel, A.;Pennacchio, L. A.;Huylebroeck, D.;Higashi, Y.;Rubenstein, J. L. R.",2013,09 Jan,http://dx.doi.org/10.1016/j.neuron.2012.11.035,0,0,
1520,Gastrointestinal and liver disease in pregnancy,"This chapter on the gastrointestinal and hepatic systems in pregnancy focusses on those conditions that are frequent and troublesome (gastro-oesophageal reflux and constipation), distressing (hyperemesis gravidarum) or potentially fatal (obstetric cholestasis, acute fatty liver of pregnancy and HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome). It also highlights the clinical challenge obstetricians may face in managing rare conditions such as the Budd-Chiari syndrome, liver transplantation, primary biliary cirrhosis and Wilson disease. The clinical presentation of liver and gastrointestinal dysfunction in pregnancy is not specific, and certain 'abnormalities' may represent physiological changes of pregnancy. Diagnosis and management are often difficult because of atypical symptoms, a reluctance to use invasive investigations and concerns about the teratogenicity of the medications. The best available evidence to manage these conditions is discussed in the chapter.© 2013 Published by Elsevier Ltd.",acid peptic disease;acute appendicitis;aflp;auto-immune hepatitis;Budd-Chiari syndrome;constipation;diarrhoea;gallbladder disease;hellp;hyperemesis gravidarum;ibd;infective hepatitis;inflammatory bowel disease;listeriosis;liver disorders in pregnancy;liver transplantation;pancreatitis;portal hypertension;pre-eclampsia obstetric cholestasis;primary biliary sclerosis;reflux oesophagitis;Wilson disease;abdominal pain;acupuncture;antibiotic therapy;appendicitis;article;Budd Chiari syndrome;chronic active hepatitis;conservative treatment;Crohn disease;diarrhea;fatty liver;gastrointestinal disease;gastrointestinal endoscopy;HELLP syndrome;human;hyperemesis gravidarum/dt [Drug Therapy];hypnosis;immunosuppressive treatment;intestine infection;intrahepatic cholestasis;irritable colon/dt [Drug Therapy];jaundice;liver disease;nausea and vomiting;peptic ulcer/dt [Drug Therapy];pregnancy;primary biliary cirrhosis;priority journal;reflux esophagitis/dt [Drug Therapy];smoking cessation;teratogenicity;ulcerative colitis;virus hepatitis;Wernicke encephalopathy/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];antacid agent/dt [Drug Therapy];antiemetic agent/dt [Drug Therapy];azathioprine;chlorpromazine/dt [Drug Therapy];colofac;cyclizine/dt [Drug Therapy];cyclosporin/iv [Intravenous Drug Administration];dicycloverine/dt [Drug Therapy];dihydrofolate reductase inhibitor;domperidone/dt [Drug Therapy];folic acid;histamine H2 receptor antagonist/dt [Drug Therapy];hydrocortisone/dt [Drug Therapy];hydrocortisone/iv [Intravenous Drug Administration];mebeverine/dt [Drug Therapy];mercaptopurine;metoclopramide/dt [Drug Therapy];metoclopramide/sc [Subcutaneous Drug Administration];omeprazole/dt [Drug Therapy];ondansetron/dt [Drug Therapy];prednisolone/dt [Drug Therapy];prednisolone/po [Oral Drug Administration];prochlorperazine/dt [Drug Therapy];promethazine/dt [Drug Therapy];proton pump inhibitor/dt [Drug Therapy];salazosulfapyridine;scopolamine/dt [Drug Therapy];scopolamine butyl bromide;sucralfate/dt [Drug Therapy];thiamine/dt [Drug Therapy];thiamine/iv [Intravenous Drug Administration];thiamine/po [Oral Drug Administration];unclassified drug;vitamin K group/po [Oral Drug Administration];zinc/dt [Drug Therapy],"Boregowda, G.;Shehata, H. A.",2013,December,http://dx.doi.org/10.1016/j.bpobgyn.2013.07.0065,0,0,
1521,Efficacy and safety of oral chelators in treatment of patients with wilson disease,"BACKGROUND & AIMS: Wilson disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms. Chelating agents (D-penicillamine, trientine) are used as first-line therapies for symptomatic patients, but there are few data from large cohorts. We assessed the safety of D-penicillamine and trientine therapy and outcomes of patients with Wilson disease. METHODS: We performed a retrospective analysis of data on 380 patients with Wilson disease from tertiary care centers in Germany and Austria, and 25 additional patients from the EUROWILSON registry. Chelator-based treatment regimens were analyzed for their effect on neurologic and hepatic symptoms and for adverse events that led to discontinuation of therapy (Kaplan-Meier estimation; data were collected for a mean of 13.3 y after therapy began). RESULTS: Changes in medication were common, resulting in analysis of 471 chelator monotherapies (326 patients receiving D-penicillamine and 141 receiving trientine). Nine of 326 patients treated with D-penicillamine and 3 of 141 patients given trientine underwent liver transplantation. Adverse events leading to discontinuation of treatment were more frequent among those receiving D-penicillamine than trientine (P = .039). Forty-eight months after therapy, hepatic deterioration was reported in only 4 of 333 patients treated initially with a chelating agent. Hepatic improvements were observed in more than 90%, and neurologic improvements were observed in more than 55%, of therapy-naive patients, and values did not differ significantly between treatments. However, neurologic deterioration was observed less frequently in patients given D-penicillamine first (6 of 295) than those given trientine first (4 of 38; P = .018). CONCLUSIONS: Chelating agents are effective therapies for most patients with Wilson disease; D-penicillamine and trientine produce comparable outcomes, although D-penicillamine had a higher rate of adverse events. Few patients receiving chelation therapy had neurologic deterioration, which occurred more frequently in patients who received trientine. © 2013 AGA Institute.",atp7b;Metabolic disorder;Wilson's disease;Wilsons disease;albuminuria/si [Side Effect];alopecia/si [Side Effect];arthralgia/si [Side Effect];article;chelation therapy;drug efficacy;drug fatality/si [Side Effect];drug safety;drug withdrawal;elastosis/si [Side Effect];erythema/si [Side Effect];fatigue/si [Side Effect];female;follow up;genotype;headache/si [Side Effect];hematuria/si [Side Effect];hirsutism/si [Side Effect];human;kidney disease/si [Side Effect];leukopenia/si [Side Effect];liver function;liver transplantation;lupus erythematosus/si [Side Effect];major clinical study;male;myalgia/si [Side Effect];nephrotic syndrome/si [Side Effect];optic neuritis/si [Side Effect];patient compliance;phenotype;polyneuropathy/si [Side Effect];pruritus/si [Side Effect];retrospective study;treatment duration;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration],"Weiss, K. H.;Thurik, F.;Gotthardt, D. N.;Schafer, M.;Teufel, U.;Wiegand, F.;Merle, U.;Ferenci-Foerster, D.;Maieron, A.;Stauber, R.;Zoller, H.;Schmidt, H. H.;Reuner, U.;Hefter, H.;Trocello, J. M.;Houwen, R. H. J.;Ferenci, P.;Stremmel, W.",2013,August,http://dx.doi.org/10.1016/j.cgh.2013.03.012,1,1,
1522,Treating neurological Wilson's disease; The expert opinion is not good enough,,brain tissue;chelation therapy;clinical feature;copper blood level;drug efficacy;editorial;evidence based medicine;genetic analysis;human;liver graft;mental disease;monotherapy;neurologist;patient safety;priority journal;randomized controlled trial (topic);Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Fox, S.",2013,01 Jul,,0,0,
1523,Panda with <<bright eyes>> in Wilson's disease,,academic failure;adolescent;case report;ceruloplasmin blood level;diffusion weighted imaging;dysarthria;dysphagia;human;hypersalivation;laboratory test;male;neurologic examination;note;nuclear magnetic resonance imaging;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Kallollimath, P.;Nagappa, M.;Sinha, S.;Saini, J.;Bindu, P. S.;Taly, A. B.",2013,January-February,http://dx.doi.org/10.4103/0028-3886.108052,0,0,
1524,Dysphagia as the first symptom in Wilson disease: A case report. [Persian],"Background: Primary manifestations of Wilson disease are diverse and may cause delayed diagnosis of the disease which will in turn defer treatment and result in subsequent neurologic and gastrointestinal complications such as dysphagia. Case Report: The patient was a 15-year-old boy who had been visited by several gastroenterologists because of dysphagia and sialorrhea. He had been prescribed with different drugs. Upper gastrointestinal tract radiography and two endoscopies were performed. After all clinical manifestations, low serum ceruloplasmin, low copper, high 24-hour copper excretion, and Kayser-Fleischer rings led to diagnosis of Wilson disease. Treatment by D-penicillamine was started. Dysphagia was cured after a few days of treatment. Neurologic symptoms improved following onetwo weeks of treatment. Conclusion: Early diagnosis of Wilson disease when different manifestations are present may help in prevention of neurologic and gastrointestinal complications.",Dysphagia;Wilson disease;adolescent;article;case report;ceruloplasmin blood level;copper excretion;dysphagia/dt [Drug Therapy];excretion;gastrointestinal endoscopy;gastrointestinal radiography;human;hypersalivation;iris disease;kayser fleischer ring;male;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Chitsaz, A.",2013,,,0,0,
1525,[Wilson's disease in the child: apropos of 20 cases]. [French],,adolescent;central nervous system;chelation therapy;child;consanguinity;early diagnosis;female;genetic screening;genetics;hemolytic anemia/et [Etiology];human;liver cirrhosis/et [Etiology];liver disease;male;Morocco/ep [Epidemiology];portal hypertension/et [Etiology];preschool child;retrospective study;review;symptom assessment;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];ceruloplasmin/an [Drug Analysis];copper;penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Idrissi, M. L.;Babakhoya, A.;Khabbache, K.;Souilmi, F.;Benmiloud, S.;Abourrazak, S.;Chaouki, S.;Atmani, S.;Bouharrou, A.;Hida, M.",2013,,,0,1,
1526,Clinical approach in wilson disease using leipzig scoring system,"INTRODUCTION: Wilson disease (WD) is an autosomal recessively inherited disorder of the copper accumulation and toxicity. It's treatable, if diagnosed early. The recognition is clear in typical clinical presentations. Unexplained liver tests abnormalities are a diagnostic challenge and require more examinations. AIMS&METHODS: Aim: To investigate the clinical features and diagnostic possibilities in WD. Material and methods: Sixty three patients with WD were analysed (22 female, 41 male), from June 2010 to March 2013, aged at the end of evaluation between 18 and 64 years. Leipzig scoring system was used for diagnosis. RESULTS: The patients were followed up from 3 months to 21 years from diagnosing. The diagnosis was based on clinical suspicion and findings, parameters of copper metabolism, ultrasonography, ophthalmological examination, liver biopsy, MRI, DNA analysis and assessment of the Leipzig scoring system at the final evaluation. Twenty seven patients (42,9%) were with liver disease alone, thirty one (49,2%) - with hepatic and neurological presentation, three with neurological features without signs of a liver injury and two asymptomatic patients. The hepatic presentation was as follows: steatosis (4/63), hepatitis 38,1% (24/63), cirrhosis in 47,6% (30/53), acute liver failure after a discontinuation of the treatment (2/63), hepatocellular carcinoma in one cirrhotic patient. The average level of the ceruloplasmin was 0,137 g/l. 24-hour urine copper was increased. D-penicillamine challenge test showed mean value 17,69 mumol/24 h of urine copper excretion. According to the Leipzig diagnostic criteria 55(87,3%) patients had a score >=4 (max.12). Eight patients had score 3, but the exclusion of another etiology and the clinical course of the disease confirmed the diagnosis. 23(36,5%) patients had Kayser-Fleischer ring and 4 - sunflower cataract. Liver biopsy was performed in 23 patients, with rodamine positive staining in 9. DNA analysis was done in 54 patients and were found mutations in 26(48,1%). CONCLUSION: WD is a treatable inherited disorder. It has to be considered in the liver diseases to prevent the delay of the recognition and the progression of the copper metabolic disorder. Our experience confirms that the Leipzig scoring system with a combination of clinical symptoms, laboratory parameters of copper metabolism, genetic testing and liver biopsy is useful for diagnosing of WD in the clinical practice.",Diagnostic approach;Leipzig scoring system;Wilson disease;scoring system;gastroenterology;European;medical decision making;diagnosis;patient;human;liver biopsy;urine;copper metabolism;DNA determination;liver disease;parameters;examination;diseases;liver;liver cell carcinoma;liver injury;echography;toxicity;acute liver failure;liver cirrhosis;hepatitis;male;female;staining;differential diagnosis;steatosis;etiology;excretion;provocation test;disease course;sunflower;cataract;mutation;metabolic disorder;laboratory;genetic screening;clinical practice;clinical feature;nuclear magnetic resonance imaging;copper;ceruloplasmin;penicillamine;dna,"Gancheva, D.;Atanassova, M.;Stamboliyska, M.;Kotzev, I.;Kaneva, M.",2013,October,http://dx.doi.org/10.1177/2050640613502900,0,0,
1527,<sup>99m</sup>Tc-mebrofenin scintigraphy in the evaluation of liver function in patients with Wilson's disease,"Wilson's disease (WD) is a rare autosomal recessive disorder that is characterized by decreased biliary copper excretion and defective incorporation of copper into ceruloplasmin, leading to copper accumulation mainly in the liver, brain and kidneys. Clinical manifestations related to copper accumulation in the liver include hepatic disease ranging from mild hepatitis to acute liver failure or cirrhosis. The purpose of this study was to establish whether <sup>99m</sup>Tc-mebrofenin dynamic hepatobiliary scintigraphy (DHBS) can be used to assess liver function in WD. Material and methods We studied 37 consecutive WD patients treated with zinc and/or penicillamine (18 males and 19 females; mean age 39+/-4 years) with clinical evidence of hepatic disease. All patients underwent standard biochemical liver function tests, including ALT, AST,GGT, AP, TOT BIL, ALB, serum copper and ceruloplasmin and 24-h urinary copper excretion, and DHBS with <sup>99m</sup>Tc mebrofenin. Liver biopsies were performed in all WD patients. Liver tissue was examined for routine liver histology (grading and staging of fibrosis) and hepatic copper content. DHBS acquisitions (30 sec/frame for 60 min) were obtained after 110 MBq <sup>99m</sup>Tc mebrofenin i. v. injection. Time-activity curves were recorded from regions of interest placed over hepatic parenchyma (H) and main intra-hepatic biliary ducts (B). The times required to reach 50% of the hepatic activity peak (50% HTmax), maximal hepatic activity (HTmax), and the time to reach 50% of decrease of HTmax (HT<inf>1/2</inf>) were calculated. Furthermore, the times at biliary maximum peak counts (BTmax) and to half of peak activity (BT1/2 ) were calculated. Quantitative scintigraphic results were compared to biochemical parameters and liver histopathology. Results All patients showed low levels of serum ceruloplasmin and copper, respectively (3.05+/-0.2mg/dl and 57+/-18mug/dl) and high 24h urinary copper excretion (201+/-42mug/24h). According to Metavir fibrosis staging, 16 patients (43%) were classified as F1, 7 as F2 (19%), 8 as F3 (22%) and remaining 6 as F4 (16%). The analysis of DHBS quantitative data showed, in almost patients, slow hepatic uptake (>HTmax) and hepatobiliary excretion (>HT<inf>1/2</inf>). A positive correlation was observed between histological findings and 50% HTmax (p= 0.004), HTmax (p=0,001), HT<inf>1/2</inf> (p=0.006) and BTmax (p=0.02) values. Furthermore, on multivariate analysis, a statistically significant correlation was found between 50% HTmax, HTmax, HT<inf>1/2</inf>, BTmax and high degree of fibrosis (F4) vs other degree of fibrosis. With the exception of bilirubin (p<0.01), no correlation was found between biochemical liver function tests and DHBS parameters. Conclusions This study showed the clinical utility of the DHBS as non-invasive diagnostic modality for evaluating the degree of liver fibrosis, making it possible to reduce the number of liver biopsies in the long-term follow-up of WD patients.",human;liver function;scintigraphy;nuclear medicine;molecular imaging;patient;Wilson disease;liver;fibrosis;excretion;parameters;liver function test;liver disease;liver biopsy;staging;liver cirrhosis;acute liver failure;hepatitis;histopathology;multivariate analysis;diagnosis;hepatobiliary scintiscanning;parenchyma;injection;male;liver histology;copper blood level;autosomal recessive disorder;kidney;bile duct;ceruloplasmin blood level;follow up;liver fibrosis;brain;female;mebrofenin;technetium 99m;copper;ceruloplasmin;penicillamine;bilirubin;zinc,"Serra, A.;Sini, M.;Loi, G. L.;Sorbello, O.;Mighela, M.;Faa, G.;Demelia, L.;Piga, M.",2013,March,http://dx.doi.org/10.1007/s40336-013-0001-7,0,0,
1528,Nanoparticles based metal chelation therapy in animal models of copper toxicity associated diseases,"Background: Animal models of Wilson's disease rarely exhibit neurological impairments and brain copper accumulation impeding the development of novel therapeutic approaches to treat neurological manifestations in Wilson's disease patients. Aim: The aim of this study was to (1) investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100g b.w.) daily for 90 days on copper and zinc levels in liver and brain tissues, biochemical parameters and neurobehavioral functions of male Wistar rats, and (2) therapeutic efficacy of orally administered D-penicillamine encapsulated alginate/chitosan nanoparticles (NPs) for 90 days in copper intoxicated rats. Results: Copper intoxicated animals showed significantly decreased serum acetyl choline esterase (AChE) activity, increased expression of hepatic MT-I gene, impaired neuromuscular coordination and spatial memory along with significant increase in liver (99.1%) and hippocampus (73%) copper content; and interestingly, 40.7% decrease and 77.1% increase in hepatic and hippocampus zinc content respectively compared to control rats. Massive grade 4 copper depositions and grade 1 copper associated protein in hepatocytes of copper intoxicated rats was substantiated by rhodanine and orcein stains respectively. Copper intoxicated rats demonstrated swelling and increase in number of astrocytes with copper deposition in choroid plexus. Degenerated neurons with pyknotic nuclei were also observed in the brain sections of Cu intoxicated rats. D-penicillamine NPs of mean size (275 nm) and encapsulation efficiency (35%) were synthesized. HPLC studies demonstrated increased concentration of D-penicillamine by NPs therapy compared to conventional D-penicillamine therapy in liver and brain tissues. NPs based therapy resulted in significant reduction of liver and brain copper content with improvement in neurological functions. Conclusion: The study show the first evidence in vivo that D-penicillamine encapsulated NPs may reverse impairments caused by chronic copper intoxication to a significant extent in Wistar rats.",chelation therapy;animal model;toxicity;diseases;Indian;liver;rat;therapy;brain;concentration (parameters);hippocampus;Wistar rat;brain tissue;Wilson disease;nerve cell;serum;choroid plexus;encapsulation;intoxication;human;astrocyte;swelling;stain;liver cell;patient;male;spatial memory;gene;parameters;high performance liquid chromatography;nanoparticle;metal;copper;penicillamine;zinc;rhodanine;protein;cholinesterase;acetylcholine,"Pal, A.;Badyal, R. K.;Vasishta, R. K.;Thapa, B. R.;Prasad, R.",2013,March,,0,0,
1529,10th ISTERH Conference,"The proceedings contain 172 papers. The topics discussed include: monitoring of body iron metabolism in health and disease; elemental speciation analysis in human health assessment; the promise of copper lowering therapy with tetrathiomolybdate in the cure of advanced previously incurable cancer and treatment of inflammatory diseases; copper dysfunction as a risk for Alzheimer's disease: predictive value of MCI conversion into dementia, meta-analytic evidence of increased copper and non-ceruloplasmin copper in AD and new studies on ATP7B gene variants; a century of progress for the diagnosis of Wilson disease; zinc and aging: an introduction; zinc deficiency anemia in patients with chronic kidney disease (CKD); zinc, diabetes mellitus and cardiovascular disease; and serum zinc concentration and C-viral chronic liver disease in the aged.",human;health;predictive value;inflammatory disease;iron metabolism;neoplasm;diagnosis;Wilson disease;risk;aging;dementia;gene;therapy;monitoring;chronic kidney disease;patient;zinc deficiency;anemia;diabetes mellitus;cardiovascular disease;zinc blood level;chronic liver disease;Alzheimer disease;copper;zinc;tetrathiomolybdic acid;ceruloplasmin,Anonymous,2013,,,0,0,
1530,Utility of zinc acetate treatment in 15 patients with childhood onset wilson disease: A single center experience,"Treatment of Wilson disease is based on the use of copper chelators to promote copper excretion from the body, or use of zinc to reduce copper absorption in the ileum. Here we report the utility of zinc acetate therapy for Wilson disease in children. Fifteen patients including 6 males and 9 females, were treated with zinc acetate. Before treatment, nothing was given to 6 patients, 5 were treated with penicillamine, and 4 were with trientine. Median levels of liver function measured at zero months, 6 months, and 1 year were as follows: aspartate aminotransferase 48, 35, and 33 IU/l; alanine aminotransferase 71, 25, and 46 IU/l; mu-glutamyltranspeptidase 49, 46, and 55 IU/l. The median value of spot urinary copper was 1112 mug/l (0.15 mug/mg/creatinine) with the use of a chelator, and 141 mug/l (0.10 mug/mg/creatinine) without the use of a chelator. Three patients experienced nausea, and one experienced oral cavity discomfort. This study shows that zinc acetate therapy is an effective treatment for childhood onset of Wilson disease.",human;childhood;patient;Wilson disease;therapy;male;child;mouth cavity;ileum;absorption;nausea;liver function;excretion;female;zinc acetate;copper;chelating agent;trientine;penicillamine;gamma glutamyltransferase;alanine aminotransferase;aspartate aminotransferase;zinc,"Kondou, H.;Hasegawa, Y.;Tachibana, M.;Miyahara, Y.;Miyoshi, Y.;Hamada, Y.;Sakai, N.;Ozono, K.",2013,November,,0,1,
1531,The promise of copper lowering therapy with tetrathiomolybdate in the cure of advanced previously incurable cancer and treatment of inflammatory diseases,"Tetrathiomolybdate (TM) complexes copper with protein in a strong tripartite complex. This complex with food protein is excreted in the stool causing a negative copper balance. In the blood this complex, TM, free copper, and albumin, renders free copper unavailable and nontoxic. TM, developed for Wilson's disease, is very effective for the neurologic presentation, for which no other drug is optimal. Lowering copper to intermediate levels with TM, levels high enough to avoid clinical deficiency, inhibits many cytokines, such as those promoting fibrotic, inflammatory, autoimmune diseases, and cancer. TM is efficacious in mouse models of pulmonary fibrosis and cirrhosis, inhibiting transforming growth factor beta (TGFbeta) and tumor necrosis factor alpha (TNFalpha). TM is efficacious in mouse models of inflammatory disease involving liver and heart, and four mouse models of immune modulated disease. In the human, TM reached both primary endpoints in a one year randomized controlled trial in primary biliary cirrhosis, an autoimmune attack on bile ducts. TM has great promise in the disease areas of fibrosis,inflammation, and autoimmunity. Wherever steroids are useful, TM will be better and safer. Most excitingly, recent developments show that TM can cure advanced, previously incurable, metastatic cancer. Tumor growth requires angiogenesis (Folkman). Many angiogenic promoters are copper dependent, particularly those active at the micrometastatic cancer level. MAJOR CLUE: TM COMPLETELY INHIBITED CANCER GROWTH IN THE HER/2neu MOUSE GENETIC MAMMARY CANCER MODEL. Micro clusters of cancer cells, still there after a year of TM therapy, couldn't grow because of a lack of angiogenesis, while all controls had large cancers. Human trials ignored this clue, and tried TM only only against advanced cancers. These can recruit many promoters, many not copper dependent, and only modest effects in these trials led to little interest. Now, two US groups are curing metastatic cancer with TM by harking back to the mouse clue. One group requires conventional suppression to no evidence of disease (NED) , although the disease is considered incurable because of micrometastases. After three years of TM the cancer is cured, with 10 different advanced metastatic, heretofore incurable cancers. The second group uses TM from the beginning, and conventional therapy plus certain therapies aimed at cancer metabolic vulnerabilities, curing many patients with different metastatic cancers. We have begun a randomized controlled trial of TM in micrometastatic osteosarcoma in dogs. It appears TM can cure many previously hopeless case of cancer.",therapy;neoplasm;inflammatory disease;human;mouse;mouse model;metastasis;angiogenesis;randomized controlled trial;promoter region;copper metabolism;cancer cell;lung fibrosis;tumor growth;liver cirrhosis;micrometastasis;blood;autoimmunity;inflammation;bile duct;primary biliary cirrhosis;autoimmune disease;protein intake;fibrosis;heart;liver;advanced cancer;patient;osteosarcoma;dog;Wilson disease;tetrathiomolybdic acid;copper;transforming growth factor beta;protein;albumin;steroid;cytokine;tumor necrosis factor alpha,"Brewer, G. J.",2013,November,,0,0,
1532,Zinc in Human Health: It's discovery 50 years ago and the current impact,"The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytatecontaining cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.",human;health;zinc deficiency;patient;infection;malabsorption;cereal;chronic disease;cognitive defect;sickle cell anemia;protein intake;immunocompetent cell;acute diarrhea;common cold;growth retardation;Middle East;dwarfism;macular degeneration;chronic liver disease;cellular immunity;child;aged;prevention;blindness;zinc metabolism;chronic kidney disease;second messenger;Wilson disease;zinc;enzyme;transcription factor;antioxidant;antiinflammatory agent,"Prasad, A. S.",2013,November,,0,0,
1533,Wilson's disease associated with pancreatitis,"A 14-year-old girl presented with a 1-month history of abdominal pain and distention. A diagnosis of Wilson's disease was established, and zinc acetate therapy was initiated. An associated pancreatitis was diagnosed on presentation, based on elevated serum amylase and an enlarged pancreas ultrasonically. Subsequently, regular follow up disclosed no abdominal pain, with repeatedly normal serum amylase level and a normal pancreas on ultrasonography. Since abdominal pain is a common symptom in Wilson's disease on presentation, this possibility should be considered in untreated patients. It is concluded that pancreatitis may be associated with Wilson's disease, possibly because of copper deposition in the pancreas, and is probably responsive to copper chelation therapy.",pancreatitis;Indian;gastroenterology;society;abdominal pain;pancreas;amylase blood level;human;therapy;chelation therapy;girl;patient;echography;follow up;diagnosis;female;copper;zinc acetate,"Kumar, T. S. R.;Preethi, S.;Hariprasad;Azimudeen;Manoj;Chitra;Manimaran;Murali;Venkateswaran, A. R.",2013,November,http://dx.doi.org/10.1007/s12664-013-0417-z,0,0,
1534,Hypocupremia associated cytopenia and myelopathy: A national retrospective review,"Background: Copper is an essential trace element that is involved in a number of important enzymatic processes throughout the body. Recent single case reports and small studies have shown that deficiency of copper can cause reversible haematological changes and irreversible neurological injury. Introduction: We chose to undertake a national study, looking at all cases of copper deficiency in Scotland over a 5 year period using information from a national reference laboratory. Results: From 16 identified patients, we determined that 86% had both haematological and neurological features of copper deficiency, while 18% had haematological features only at presentation. Twelve of the sixteen patients had high serum zinc concentrations (>18 mum/L)due to zinc containing dental fixatives (9 patients), oral zinc replacement therapy following proximal bowel resection (1 patient), Wilson's Disease treated with zinc (1patient) and skin burns requiring topical zinc therapy (1 patient). 94% of patients had haematological features as an initial manifestation of copper deficiency, which included anaemia, thrombocytopenia and neutropenia. Patients who underwent later bone marrow testing had appearances in keeping with refractory cytopenia with multilineage dysplasia, refractory anaemiawith excess of blasts, unclassifiedmarrowdysplasia or probable myelodysplasia (MDS). 75% of patients had neurological symptoms or signs, including progressive walking difficulties and paraesthesia, or gait difficulties without sensory signs. Clinical examination was in keeping with spastic paraparesis (either with or without sensory neuropathy). Magnetic resonance imaging (MRI) showed multifocal T2 hyper intense foci in the sub cortical white matter, and atrophy of the cerebrum and cerebellum was also seen on computerised tomography (CT).MRI of the spinal cord showed signal change in the dorsal columns either in the cervical or thoracic cord. 93% of cytopenias responded to copper replacement and addressing the original cause of the copper deficiency, but only 25% of patients had improvement in their neurological function, while 33% deteriorated and 42% remained unchanged. Conclusions: Our study demonstrates that copper deficiency is an under-recognised cause of several types of cytopenia, which are reversible but can progress to significant neurological injury if left untreated. We illustrate the importance of identifying these patients early to prevent irreversible neurological injury.",spinal cord disease;myelodysplastic syndrome;cytopenia;human;patient;copper deficiency;injury;nuclear magnetic resonance imaging;case report;neurologic disease;bone marrow;brain;neutropenia;zinc blood level;thrombocytopenia;laboratory;cerebellum;computer assisted tomography;refractory cytopenia with multilineage dysplasia;walking difficulty;spastic paraplegia;anemia;United Kingdom;clinical examination;therapy;gait;burn;sensory neuropathy;paresthesia;white matter;atrophy;intestine resection;substitution therapy;spinal cord;spine;Wilson disease;zinc;copper;fixative;trace element,"Gabreyes, A.;Abbasi, H.;Forbes, K. P.;McQuaker, G.;Duncan, A.;Morrison, I.",2013,May,,0,0,
1535,Mixed-type polyneuropathy in Wilson's Disease,"Wilson's Disease (WD) is an autosomal recessive disorder of abnormal copper metabolism witch predominantly affects the central nervous system and the liver. Peripheral nervous system involvement is rarely reported in the context of WD and not well characterized. Here we describe a WD patient with peripheral neuropathy. A 58-year-old male suffering from WD on therapy with trientine referred to our center because of mild distal limb weakness with hypoesthesia. Clinical evaluation showedmild leg weakness with foot drop and hyporreflexia. A nerve conduction study was performed using standard techniques (Medtronic Keypoint v5.09). Distal motor latency, F-wave latency, motor nerve conduction velocity and CMAP were evaluated in the deep peroneal, posterior tibial, median and ulnar nerves; sensory nerve conduction velocity and SAP were measured in the sural, superficial peroneal,median, ulnar and radial nerve. No other cause of polyneuropathy was found. Electroneurographyc findings suggested an asymmetric length-dependent sensory-motor neuropathy of mixed type. We confirmed peripheral nervous system involvement in WD. According to the literature, also our findings showed both myelin and axonal damage. Polyneuropathy may appear despite therapy, although a iatrogenic contribution cannot be excluded.",electroneurology;polyneuropathy;society;Wilson disease;therapy;latent period;peripheral nervous system;liver;copper metabolism;human;peripheral neuropathy;nerve conduction;hypesthesia;patient;limb weakness;clinical evaluation;leg;weakness;peroneus nerve paralysis;motor nerve conduction;male;ulnar nerve;sensory nerve conduction;radial nerve;motor neuropathy;central nervous system;autosomal recessive disorder;trientine;myelin,"Aste, R.;Salaris, E.;Pische, M. G.;Floris, E.",2013,November,http://dx.doi.org/10.1016/j.clinph.2013.06.097,0,0,
1536,"Case report: Brain MRI revealing the rare but distinctive ""Double Panda Sign"" in a patient with wilson's disease","Background and Purpose: Wilson's disease is a clinically rare, important genetic disorder wherein copper accumulates in the liver, brain, and other tissues and may be fatal if not recognized and treated when symptomatic. Methods: A 29-year-old woman presented with painful contractures of her left hand, dysarthria, dysphagia, and gait disturbance. Symptoms had initially begun 4 months prior with right hand eversion and contracture for 2 weeks with spontaneous resolution. She denied exposure to toxins, substance abuse, or similar family history. Results: She had normal mental status, dysarthria, hypophonia, dystonia, chorea, and broad-based gait. Early Kayser-Fleisher rings were seen on ophthalmologic exam. Diagnosis was confirmed with low serum ceruloplasmin and high urine copper. Liver function tests were normal. Brain MRI showed bilateral T2 hyperintensities involving the putamen, thalami, and brainstem with the characteristic ""double panda sign."" Conclusions: The ""double panda sign"" characteristic for Wilson's has been described in few reports. It is formed by the ""face of the giant panda"" in the midbrain [1], and the ""face of the miniature panda"" in the pons [2] and is caused by preservation of normal signal intensity in the red nuclei and lateral pars reticulata of the substantia nigra, hypertinensity in the tegmentum, and hypointensity of the superior colliculus. The ""face of the miniature panda"" is seen within the pontine tegmentum, demarcated by hypointensity of the medial longitudinal fasciculi and central tegmental tracts, contrasted by hyperintensity of the cerebral aqueduct. She was treated with D-penicillamine, zinc, and a low-copper diet with slow improvement of symptoms. (Figure presented).",human;patient;neuroimaging;brain;case report;society;Wilson disease;nuclear magnetic resonance imaging;contracture;gait;dysarthria;tegmentum;genetic disorder;chorea;hand;urine;dystonia;mental health;tissues;substance abuse;preservation;family history;brain aqueduct;diagnosis;ceruloplasmin blood level;liver function test;liver;pons;mesencephalon;Ailuropoda;exposure;brain stem;red nucleus;substantia nigra;thalamus;superior colliculus;medial longitudinal fasciculus;putamen;diet;dysphagia;female;copper;penicillamine;toxin;zinc,"Jimenez, R.;Suradi, Y.;Freeman, M.",2013,April,http://dx.doi.org/10.1111/jon.12014,0,0,
1537,Outcome of hepatic Wilson's disease at 6 months from diagnosis: Response to combination of D-Pencillamine and zinc therapy in a tertiary care centre in India,"Thirty three prospectively enrolled cases of Hepatic Wilson's disease were given D-Pencillamine (10-20mg/kg/day) and zinc therapy. Combination therapy (administered at intervals to avoid interference) was shifted to zinc only therapy after the normalization of transaminases. Normal transaminases and negative copper balance at 12 months on therapy were considered successful therapy. Time of clinical and biochemical response (AST & ALT <60 IU/L) were calculated. Thirty three cases (median age of 127.21+/- 42.27 months) were enrolled. Liver transplantation (LT) was offered to 5 cases with fulminant hepatic failure. Of the rest 28 cases with chronic liver disease (CLD): 4 of the 5 presenting as acute on chronic liver failure (ACLF) and 3 of the 17 decompensated CLD required LT. All 6 compensated CLD, 1 of 5 ACLF and 14 of 17 with decompensated CLD were successfully treated with medical therapy. Twenty one (75%) of the 28 cases successfully treated on medical therapy. Twenty cases showed clinical response within 6 months and 1 case at 12 months. Fifteen cases showed biochemical response within 6 months and remaining 6 cases by 12 months. Conclusions: 75% cases improved on combination therapy with response within 6 months.",therapy;diagnosis;India;tertiary care center;metabolism;Wilson disease;acute on chronic liver failure;fulminant hepatic failure;liver transplantation;chronic liver disease;copper metabolism;zinc;aminotransferase,"Alam, S.;Khanna, R.;Sood, V.",2013,September,http://dx.doi.org/10.1007/s10545-013-9633-z,0,1,
1538,Prediction of poor outcome on medical therapy at the time of diagnosis in Wilsons Disease (WD) presenting as Chronic Liver Disease (CLD): Is the new wilsons index helpful?,"Twenty eight cases of WD presenting as CLD were managed with D Pencillamine and zinc. Univariate and multivariate analysis was done to see the association of the risk factors with poor outcome (liver transplantation or death) at the time of diagnosis. Four of 5 presenting as acute on chronic liver failure (ACLF), 3 of 17 as decompensated CLD had poor outcome. All 6 compensated CLD, 1 of 5 ACLF and 14 of 17 with decompensated CLD improved. On univariate analysis, bilirubin, AST, ALT, Child Pughs score and New Wilson's index score were significantly higher in those with poor outcome. On logistic regression analysis significant association with poor outcome were high ALT (adjusted OR 1.062, 95% CI 1.007-1.12, p= 0.015) and low albumin (adjusted OR 0.052, 95% CI 0.005-0.56, p= 0.028). With 20 IU increase in ALT the odd's ratio increased by 3.3(95% CI: 1.15 to 9.58), and 1 g decrease in albumin increases the odd's ratio by 0.95 (95% CI: 0.44-0.995). Conclusion: High ALT and low albumin are independently associated with poor outcome on medical therapy inWDpresenting as CLD. Child Pugh's and New Wilson's index scores did not show significant association with poor outcome.",therapy;diagnosis;Wilson disease;chronic liver disease;metabolism;prediction;human;child;acute on chronic liver failure;multivariate analysis;univariate analysis;death;liver transplantation;logistic regression analysis;risk factor;albumin;zinc;bilirubin,"Alam, S.;Khanna, R.;Sood, V.;Rawat, D.",2013,September,http://dx.doi.org/10.1007/s10545-013-9633-z,0,0,
1539,Joint manifestation and bone changes in patients with wilsone disease,"Background Wilsone disease (WD) is an autosomal recessive hereditary metabolic disorder leading to the pathologic accumulation of copper in various organs, especially in the brain and liver. The most frequent clinical manifestations consist of the liver form and neurological-psychiatric form. Problems with the joints are common and affect a high percentage of patients suffering from WD. Joint involvement in WD patients has not been studied in details so far. Treatment of WD is very effective. One approach involves treatment with penicilamin. Alternatively zinc can be used. Treatment must be life-long. On the other hand treatment of arthropathy is difficult and mostly not very successful. The aim was to determinate the location and types of changes in the affected joints in a set of patients diagnosed with WD and to determinate, if there is any relation between the type of treatment and joint manifestation. Objectives To evaluate changes in clinical and image assessment of patients with WD after 5 year period. Methods From the group of 41 patients with diagnose of WD was selected a group of 10 patients with arthropathy. They were evaluated for the history, clinical assessments, X-ray and sonography of the affect joins, bone densitometry of the hip and lumbar spine. The complete assessment was repeated after 5 years. Results Ages ranged from 19 to 61 years, average age was 36 years. There were 8 women and 2 men. The knee was the most frequently involved joint. Other involvement joints (in decreasing order of frequency) were wrist, schoulders, metacarpofalangeal joints, ankles and lumbosacrale spine. Patients had involvement of 1-15 joints/patient. Physical finding consisted mainly of pain, pain on motion, stiffness and crepitus in affected joints. 5 patients had decrease range of motion in abnormal joints and 2 had hypermobility. During 5 years period 5 patients had arthritis (clinical and sonography detected) with duration from 1 months to 2 years. Radiographic changes included joint space narrowing, ostephytes, cysts, soft tissue calcification and bone fragmentation. 3 patients had osteoporosis and 3 osteopenia. After 5 years period there increase number of affected joints, radiographic changes and decrease T- score in the lumbar spine in these set of patients. More radiographic changes can be seen in patient treated with penicialamin than with zinc. Conclusions Wilson's disease is connected with morphological damage to the skeleton, premature arthrosis, arthritis and osteoporosis. Although all patients were treated by penicillamine or zinc and neurological-psychiatric and liver manifestation were stable there were progresion of artropathy. More changes have patients on penicilamin. Further studies with great number of patients are needed.",patient;human;rheumatology;rheumatic disease;bone;liver;arthritis;osteoporosis;pain;lumbar spine;arthropathy;echography;spine;ankle;autosomal recessive inheritance;wrist;skeleton;osteopenia;osteoarthritis;knee;male;brain;hip;soft tissue calcification;cyst;bone densitometry;joint cavity;range of motion;female;X ray;hospital patient;metabolic disorder;rigidity;clinical assessment;Wilson disease;zinc;penicillamine;copper,"Sleglova, O.;Marecek, Z.",2013,,http://dx.doi.org/10.1136/annrheumdis-2013-eular.2083,0,0,
1540,Analysis of clinical feature of Wilson's disease in 181 cases,"Objective: To explore clinical feature of Wilson's disease. Methods: 181 cases of Wilson's disease were retrospectively studied. Results: The male patients were more than female patients significantly. The numbers of patients of age between 8 and 29 were significantly more than those in other age periods. Liver and extrapyramidal symptoms were two main onset symptoms. 40-60 % patients hepatic function had been damaged. More than 95 % patients had dysfunction on liver ultrasound, encephalic CT and encephalic MRI. Penicillamine were generally effective. The mainly death cause was liver failure. Conclusion: Wilson's disease often occurs in male and youths. Liver and extrapyramidal symptoms are the main clinical symptoms. Liver ultrasound and encephalic CT/MRI should be one of auxiliary diagnosis devices. Hepatic function has been damaged before the occurrence of symptoms. Penicillamine were generally effective.",liver;Asian;clinical feature;Wilson disease;human;patient;ultrasound;male;extrapyramidal symptom;liver function;female;devices;diagnosis;juvenile;liver failure;cause of death;nuclear magnetic resonance imaging;penicillamine,"Shaoquan, Z.;Li, M.;Jing, L.",2013,June,http://dx.doi.org/10.1007/s12072-013-9429-0,0,0,
1541,Wilson's disease (WD) in Malaysia-a single center experience,"Background/aims: Wilson's disease is an inherited autosomal recessive disorder with defective biliary excretion of copper leading to its accumulation in the liver and brain. We report the clinical features, treatment and outcome of WD patients in our center. Methods: All WD patients (n = 35) referred to our center from 2000 to 2012 were studied retrospectively. Results: The median age at diagnosis was 16 years [range = 8-59] with 60 % females. Five (14.3 %) gave positive history of parental consanguinity. Thirty one (88.6 %) of the patients presented with hepatic involvement only and 4 (11.4 %) had mixed neurologic and hepatic involvement. Nine (25.7 %) were fulminant WD, 14 (40 %) chronic WD with hepatic decompensation and 12 (34.3 %) without hepatic decompensation. All patients had serum ceruloplasmin below 0.2 g/L [median = 0.12 g/L, range =<0.06-0.24], 27 (77.1 %) had Kayser-Fleischer rings and 25 (83.3 %) had urinary copper excretion above 1.6 umol/day [median = 6.34 umol/day, range = 1.71-65.07]. The first line treatments were penicillamine monotherapy (54.3 %), penicillamine plus zinc (42.9 %) and one (2.8 %) did not receive any treatment because she died soon after admission. Thirteen (38.2 %) of the penicillamine patients developed complications namely haematuria (n = 2), proteinuria (n = 1), haematological (n = 1), IgA nephropathy (n = 1), hyperprolactinaemia (n = 1), myasthenia gravis (n = 1), breast gigantism (n = 1), mucositis (n = 1), anaemia (n = 1) and rashes (n = 4). Thirteen patients had change in medications to trientine (n = 6), zinc (n = 3), trientine plus zinc (n = 2) and penicillamine plus zinc (n = 2). One patient received liver transplantation because of poor response to penicillamine therapy. The median duration of follow-up was 24 months (0.06-132). At the end of follow-up, 37.1 % died and the mortality rate in fulminant WD was 77.8 %. Conclusions: WD in our population affects more females, diagnosed at young age and mainly chronic WD with hepatic decompensation. All patients had low ceruloplasmin and high proportion had Kayser- Fleischer rings. Intolerance to penicillamine occurred in 38.2 %. The mortality rate was 37.1 %.",liver;Asian;Malaysia;human;patient;decompensated liver cirrhosis;follow up;female;mortality;hematuria;population;diagnosis;proteinuria;therapy;liver transplantation;monotherapy;biliary excretion;drug therapy;rash;anemia;mucosa inflammation;gigantism;breast;excretion;clinical feature;myasthenia gravis;ceruloplasmin blood level;hyperprolactinemia;brain;consanguinity;immunoglobulin A nephropathy;autosomal recessive disorder;penicillamine;zinc;copper;trientine;ceruloplasmin,"Shahar, H.;Tan, S. S.;Shamsul, A. I.;Omar, H.",2013,June,http://dx.doi.org/10.1007/s12072-013-9429-0,0,1,
1542,Trientine encapsulated nanoparticles can chelate out hepatic and brain copper and reverse the neurological impairments caused by chronic cu intoxication,"Animal models of Wilson's disease rarely exhibit neurological impairments and brain copper accumulation impeding the development of novel therapeutic approaches to treat neurological manifestations in Wilson's disease patients The aim of this study was to (1) investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g B.W.) daily for 90 days on copper and zinc levels in liver and brain tissues and, neurobehavioral functions of male Wistar rats, and (2) therapeutic efficacy of orally administered Trientine dihydrochloride encapsulated alginate/chitosan nanoparticles (NPs) for 90 days on copper intoxicated rats. Copper administered animals exhibited significantly decreased serum AChE activity, increased hepatic metallothionein-I gene expression, impaired neuromuscular coordination and spatial memory compared to control rats. Copper intoxicated rats showed significant increase in liver, hippocampus and kidney tissues copper content (99.1, 73 and 74.9 % increase respectively), 40.7 % reduction in hepatic zinc content and interestingly, 77.1 % increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive grade 4 copper deposition and grade 1 copper associated protein in hepatocytes of copper intoxicated rats was substantiated by rhodanine and orcein stains respectively. Copper intoxicated rats demonstrated swelling and increase in number of astrocytes, copper deposition in choroid plexus and neuronal degeneration. Trientine NPs of mean size (355 nm) and encapsulation efficiency (28 %) were synthesized. Nanoparticles based therapy resulted in significant reduction of hepatic and brain Cu content. HPLC studies demonstrated increased concentration of Trientine by NPs therapy compared to conventional Trientine therapy in liver and brain tissues. In conclusion, present study show the first evidence in vivo that Trientine encapsulated NPs may reverse impairments caused by chronic copper intoxication to a significant extent in Wistar rats.",brain;intoxication;Asian;liver;rat;therapy;hippocampus;brain tissue;Wistar rat;serum;kidney parenchyma;human;patient;gene expression;Wilson disease;spatial memory;encapsulation;nerve cell degeneration;choroid plexus;astrocyte;swelling;stain;male;liver cell;urine;animal model;high performance liquid chromatography;trientine;nanoparticle;chelate;copper;zinc;metallothionein I;rhodanine;protein,"Pal, A.;Vasishta, R. K.;Badyal, R. K.;Prasad, R.",2013,June,http://dx.doi.org/10.1007/s12072-013-9429-0,0,0,
1543,Long term follow-up of wilson disease patients diagnosed in childhood: Reasons for treatment changes,"Objectives and study: Wilson's disease (WD) is a genetic disorder characterized by copper accumulation mainly in the liver. The treatment is based on chelators, and/or zinc. Efficacy of monotherapy with zinc has been questioned by Weiss et al. [1]. Aim: to evaluate reasons for treatment changes in WD patients diagnosed in childhood. Methods: 44 patients with WD, referred to our Department of Pediatrics (1984-2012), were analyzed. 42 had hepatic presentation and 2 were recruited for family screening. For each patient, the type of treatment carried out was classified in: d-penicillamine; zinc salts; combination of d-penicillamine and zinc. Reasons for therapy changes were: treatment failure, adverse events, patient demand (not linked to adverse events) and maintenance regimen. Weexcluded from our analysis, discontinuation of treatment linked to shift to maintenance therapy.Wecalculated the duration of each block of treatment until a change of medication or until the end of the follow-up period. We analyzed events of treatment changes using Kaplan-Meier estimation. Results: 44 (31 males, median age at diagnosis = 5.9 years, range = 1-16.9) of the 48 evaluated patients, were selected for treatment analysis. Changes in medical treatment were common events resulting in a total of 79 treatment blocks (32 penicillamine therapy, 35 zinc therapy and 12 combination therapy). Of these, 76 (31 penicillamine therapy, 34 zinc therapy and 11 combination therapy) were suitable for analysis. A change in medication due to treatment failure or adverse events, not linked to the transition to maintenance therapy, was observed in 4 of 34 zinc blocks (12%), 13 of 31 penicillamine blocks (42%) and 4 of 11 combination blocks (36%). Discontinuation due to adverse events was most common in patients receiving penicillamine with 6 (5 penicillamine, 1 combination) of 42 block treatments stopped for this reason. A change in medication due to treatment failure was observed in 16 blocks of 76 (21%): 8 of 31 penicillamine treatments (26%), in 4 of 34 zinc blocks (12%) and 4 of 11 combination blocks (36%). This reached statistical significance comparing zinc versus combination therapy, but not zinc with penicillamine. Among treatment failure blocks, noncompliance to therapy was pointed out in 1 of 8 pencillamine treatments (12%), 2 of 4 zinc (12%) and 4 of 4 combination treatments (100%). Conclusion: Therapy discontinuation for treatment failure and/or adverse events was more common on penicillamine than on zinc. Differently from Weiss data (1), our study confirmed that zinc monotherapy is effective in controlling liver disease in patients with WD, diagnosed and treated since childhood.",human;follow up;Wilson disease;patient;childhood;therapy;treatment failure;drug therapy;monotherapy;screening;pediatrics;liver disease;statistical significance;diagnosis;Kaplan Meier method;liver;maintenance therapy;genetic disorder;male;zinc;penicillamine;chelating agent;zinc derivative;copper,"Ranucci, G.;Di Dato, F.;Tufano, M.;De Micco, I.;Nunziata, F.;Leone, F.;Iorio, R.",2013,30 Sep,http://dx.doi.org/10.1016/j.dld.2013.08.161,0,1,
1544,Levodopa-responsive parkinsonism and autonomic (small fiber) dysfunction in patients with Wilson's disease (WD),"Background: Autonomic dysfunction has been rarely described in WD patients. Objective: To describe a series of patients with WD, levodoparesponsive parkinsonism and autonomic dysfunction. Methods: After IRB approval, we evaluated 4 patients with WD and parkinsonism for the presence of neuromuscular dysfunction and performed water-induced skin wrinkling test - SWT (Teoh, JNNP 2008;79:835). Results: Patient 1: A 37 year old female presented with cirrhosis at age 33 was diagnosed with WD and treated with ZnSO4, penicillamine and piridoxine/complex B vitamins. Since age 35 she developed pramipexole and levodopa-responsive parkinsonism, with burning and numbness in arms and genital area and urinary incontinence. NCS/EMG was normal. Water-induced SWT revealed small fiber dysfunction (mean 4-digit wrinkling of 1). Patient 2: A 23 year old male was diagnosed with WD at age 14 and was treated with penicillamine+piridoxine. Since age 21, he developed levodopa-responsive parkinsonism, with resting tremor, weight loss, dysphagia and dysphonia. NCS/ EMG was normal but water-induced SWT was abnormal (mean wrinkling of 0.25). Patient 3: A 34 year old male presented with psychosis, behavioral dysfunction, levodopa-responsive parkinsonism and episodes of loss of consciousness. He was treated with penicillamine and complex B vitamins. NCS/EMG and water-induced SWT were normal (mean wrinkling of 4). Patient 4: A 38 year old female presented with liver dysfunction, behavior changes and parkinsonism at age 24. She was diagnosed with WD and treated with penicillamine and biperiden. Parkinsonism almost completely subsided with penicillamine. SWT was normal (mean wrinkling of 3.6). Conclusions: A subset of WD patients with levodopa-responsive parkinsonism also exhibits abnormalities on SWT (autonomic dysfunction).",human;parkinsonism;patient;neurology;fiber;Wilson disease;wrinkle;autonomic dysfunction;male;female;arm;neuromuscular disease;urine incontinence;paresthesia;liver dysfunction;consciousness;psychosis;dysphonia;dysphagia;weight reduction;tremor;behavior change;liver cirrhosis;skin;electromyogram;levodopa;penicillamine;water;vitamin;pramipexole;biperiden;pyridoxine,"Gondim, F. D. A. A.;Oliveira, I. S.;Araujo, D. F.;Melo, A. P.;Alves, L. C.;Araujo, I. T.;Vale, O. C.",2013,15 Oct,http://dx.doi.org/10.1016/j.jns.2013.07.2448,0,0,
1545,D-penicillamine versus zinc sulfate as first-line therapy for Wilson's disease,"Background: Wilson's disease (WD) is a treatable inherited copper metabolism disorder. However, there is no international consensus about the first-line therapy. Objective: Our aim was to compare the course of treatment in patients with symptomatic WD that started d-penicillamine (DPA) or zinc sulfate (ZS) as a drug of choice. Patients and methods: We included 143 consecutive, new diagnosed patients with symptomatic WD between 2005 and 2009. The decision about the first-line therapy drugwas made at the physician's discretion. Data were analyzed in subgroups with predominantly neuropsychiatric and hepaticWD. Results: Neurological and enzymatic improvements were achieved with similar frequency. In patients with neuropsychiatric WD, the probability of remaining on first-line therapy was similar for DPA and ZS (20% vs. 24% at the end of follow-up). In patients with hepatic WD, it was significantly higher for ZS (31% vs. 12%). After adjusting for type of WD, sex, age at diagnosis, and the presence of at least severe hepatic symptoms, patients treated with DPA were more likely to experience worsening (OR 3.84, 95% CI: 1.15-3.85) during the first 6 months of treatment. Patients on DPA were significantly more compliant (94% vs. 81%), but experienced more adverse effects (15% vs. 3%). Conclusions: DPA and ZS are effective in the majority of WD patients. Despite certain differences, none of them appears clearly superior. Therefore, ZS may be considered a reasonable alternative to DPA as a first-line therapy.",therapy;neurology;Wilson disease;human;patient;consensus;metabolic disorder;diagnosis;follow up;adverse drug reaction;physician;copper metabolism;zinc sulfate;penicillamine,"Czlonkowska, A.;Litwin, T.;Karlinski, M.;Czerska, M.",2013,15 Oct,http://dx.doi.org/10.1016/j.jns.2013.07.467,0,1,
1546,Wilson's disease and psychiatric disorders: Is there comorbidity or indicator of relapse?,"Introduction: Wilson's disease is an infrequent pathology resulting from a change of the ATP7B gene on the long arm of chromosome 13. This involves a reduction of the transport of copper in the bile and its accumulation in the body, notably the brain. Objective: The objective of this study is to illustrate the significance of psychiatric disorders in WD. Case report: A 25-year old woman with a personal history of Wilson's disease(WD) presented acute psychotic manifestations. The psychiatric interview finds a state of psychomotor agitation, aggressiveness and depressed mood concept with suicidal intentions. Moreover, she has a bilateral extra pyramidal syndrome. The blood levels of copper and ceruloplasmin are collapsed. The patient confirmed that she had stopped her treatment with D-penicillamine for two months ago. Discussion: WD begins in the form of a hepatic, neurological, or psychiatric disease in at least 90% of the patients. In some rare cases, the firstmanifestations of the disease can be psychiatricwhich accounts for only 10%. The disease can include later isolated behavioral problems, a schizophrenic syndrome, or a manic-depressive syndrome. The main difficulty was to establish whether psychiatric disorders are included in theWD array or not. Indeed neuropsychiatric co morbidity in the context ofWD is significant. Poor adherence to treatment, cupric balance sheet and the improvement after the reintroduction of D-penicillamine confirm a psychiatric relapse of WD. Conclusion: In WD, psychiatric manifestations can precede, complicate the somatic disorders or be independent. An early diagnosis is necessary to provide a specific treatment.",comorbidity;mental disease;relapse;neurology;Wilson disease;human;patient;brain;bile;pathology;pyramidal sign;mood;blood level;patient compliance;aggressiveness;restlessness;chromosome 13;bipolar disorder;interview;schizophrenia;morbidity;psychosis;diseases;early diagnosis;female;case report;arm;gene;penicillamine;copper;ceruloplasmin,"Mrabet, S.;Ellouze, F.;Mrad, M. F.",2013,15 Oct,http://dx.doi.org/10.1016/j.jns.2013.07.394,0,0,
1547,Increased seizure frequency due to the copper deficiency in Wilson's disease,"Background: Epileptic seizures have been reported in Wilson's disease (WD) in 6-7% of patients, mostly following the chelator therapy. Pyridoxine deficiency due to penicillamine, direct copper toxicity, pathological changes, metabolic encephalopathy and rarely copper deficiency are the attributed mechanisms for seizures. Objective: To present a patientwithWDand intractable seizures, taking chelator and antiepileptic therapy with a strict copper restricted diet. Patients and methods: A-29-year old female patient admitted to emergency unit with recurrent seizures. She had been diagnosed as WD and epilepsy in another center previously with a treatment of penicillamine, zinc acetate and carbamazepine. Complex partial and less frequent secondary generalized seizures had been started after taking penicillamine and responded well to carbamazepine initially. She complained increased daily frequency of seizures ranging from 5 to 10 in recent months. Results: Although effective serum carbamazepine level and levetiracetam add-on therapy, changed chelator therapy with trientine and oral pyridoxine, daily frequency of seizures did not reduce and low serum copper [0.3 mug/dl (70-140)] has been attributed for the seizures. Zinc acetate and strict copper restricted diet were ended. As the serum copper levels increased during followup [16 mug/dl (70-140)], seizure frequency was decreased. Conclusion: Epileptic seizures respond well to antiepileptic treatment in WD. In this case, add-on antiepileptic and pyridoxine therapy did not reduce the seizure frequency. The relation between decreased seizure frequency and increased serum copper levels shows that copper deficiency can cause intractable seizures in patients who are taking chelator therapy with a strict copper restricted diet.",neurology;seizure;copper deficiency;Wilson disease;therapy;human;patient;diet restriction;copper blood level;intractable epilepsy;anticonvulsant therapy;epilepsy;emergency ward;follow up;add on therapy;metabolic encephalopathy;serum;tonic clonic seizure;toxicity;pyridoxine deficiency;female;copper;chelating agent;carbamazepine;penicillamine;zinc acetate;pyridoxine;trientine;etiracetam,"Kaleagasi, H.;Oksuz, N.;Ozal, S.;Yilmaz, A.;Dogu, O.",2013,15 Oct,http://dx.doi.org/10.1016/j.jns.2013.07.209,0,0,
1548,A neuropsychiatric presentation of wilson's disease-case report,"Introduction: Wilson's disease (hepatolenticular degeneration), is an autosomal recessive hereditary disease of human copper metabolism, being characterised by excessive accumulation of copper in the body particularly the brain, liver, kidney and cornea. The diagnosis of Wilson's disease is easily overlooked. About half the people with Wilson's disease (40%), have neurological or liver symptoms. Psychiatric symptoms due to Wilson's disease are present in 15 % of patients. Aim: To present the case of an adolescent admitted to Clinic of Psychiatry, University Clinical Center Tuzla, initially presented with psychiatric and neurological symptoms, diagnosed at etiologic cause on the basis of biochemical abnormalities of a copper metabolisam, treated with etiological therapy and obtained therapeutic effect. Case report: An 18 years old boy admitted to Department of Psychiatry, University Clinical Center Tuzla, with prior history of behavioral disturbances in the form of disinterest in the surroundings, decreased interactions with family and with signs of aphasia. Neurological examination revealed drooling of saliva, tongue protrusion and generalized cogwheel rigidity. Symptomatic treatment started with no therapeutic efficacy. After laboratory testings were done, findings showed low serum copper and ceruloplasmin levels, and with positive Kayser-Fleischer rings on ophtalmoscopic examination by slit lamp, and computerized tomography of the head indicate neuro-degenerative disease, Wilson disease has been diagnosed. After psychiatric observation and treatment started, patient was transferred to Department of Neurology, University Clinical Centre Tuzla. The patient responded very well to therapy with D - penicillamin, Clozapin, essential phospholipids, vitamins and pyridoxin. Regular follow up advised to evaluate the outcome.",psychiatry;case report;human;Wilson disease;patient;university;therapy;liver;therapy effect;neurologic disease;copper metabolism;computer assisted tomography;adolescent;male;hospital;neurology;boy;genetic disorder;laboratory;mental disease;rigidity;tongue;diagnosis;cornea;saliva;hypersalivation;palliative therapy;neurologic examination;copper blood level;follow up;aphasia;examination;slit lamp;kidney;degenerative disease;behavior disorder;brain;autosomal recessive inheritance;copper;ceruloplasmin;penicillamine;pyridoxine;phospholipid;clozapine;vitamin,"Aljukic, N.;Sutovic, A.;Avdic, L.;Pajevic, I.;Hasanovic, M.",2013,,,0,0,
1549,Isosteric analogues of natural polyamines with altered carbon chain length and additional amino groups,"The cationic biogenic polyamines spermine (Spm) and spermidine (Spd) interact with negatively charged components of the cells and are essential for their growth and viability. Spm and Spd are positively charged at physiological pH (7.4) and the localization of the charges defines their recognition. Alteration of the carbon chain length and addition of extra amino group(s) into polyamine backbone gives rise to isosteric analogues with reduced degree of protonation. The total net charge of 1,12-diamino- 3,6,9-triazadodecane (SpmTrien), which is Spm isoster is +3 at physiological pH [1], while 1,8-diamino-3,6-diazaoctane, (Trien), which is Spd analogue, is +2. Despite these analogues have different localization and total net charge they still have some of the properties of their parent polyamines. Trien, being an excellent chelator of Cu2+ ions, is used to treat Wilson's disease when person is intolerant to penicillinamine and recently Trien was shown to ameliorate left-ventricular hypertrophy in type 2 diabetic patients [2]. Trien is a poor mimetic of Spd: it penetrates poorly inside cells, and cannot fulfill most of Spd cellular functions. However, Trien exhibits some substrate properties of spermidine/spermine N1-acetyltransferase (SSAT1) reaction [3], but its physiological acetylating enzyme is thialysine N-acetyltransferase [4]. SpmTrien is more successful mimetic of Spm: it efficiently penetrates inside cells and can fulfill some of Spm cellular functions [3]. In cells and in vivo SpmTrien is acetylated by SSAT1 and then oxidized by acetylpolyamine oxidase to Trien [3,5]. Therefore SpmTrien can be considered as a bioactive precursor of Trien.",pH;human;cell function;heart left ventricle hypertrophy;parent;proton transport;diabetic patient;precursor;Wilson disease;carbon;polyamine;trientine;acyltransferase;spermidine;penicillamine;spermine;chelating agent;oxidoreductase;enzyme;ion,"Weisell, J.;Hyvonen, M.;Khomutov, A.;Alhonen, L.;Vepsalainen, J.;Keinanen, T.",2013,July,http://dx.doi.org/10.1111/febs.12340,0,0,
1550,Different types of facial dystonias in a patient with Wilson disease treated with botulinum toxin type A,"Objective: To evaluate efficacy and safety of botulinum toxin type A (BoTN-A) treatment in a patient with Wilson disease (WD) and multiple types of facial dystonias and retrocollis. To describe the different types of abnormal movements shown by this patient. Background: WD is an autosomal recessive disorder of copper metabolism characterized by impaired excretion of this metal, resulting in its accumulation in many organs, such as liver, brain, and cornea. Clinically, patients present with psychiatric, neurological, or hepatic symptoms. BoNT treatment is the first choice approach for most focal dystonias including those associated with WD. Methods: A 20-year-old girl presented with 9 month history of abnormal behavior, mild symmetric parkinsonism, dysarthria and severe short duration crisis of retrocollis and blepharospasm. Neurologic examination demonstrated Kayser-Fleischer rings, grinning facial expresion, sustained open mouth smile, dystonic dropped jaw and mild symmetric parkinsonism. Irregular and frequent crisis of severe blepharospasm and retrocollis were present. Brain MRI showed bilateral basal ganglia T2 and FLAIR hyperintensity involving midbrain, thalami, putamen and white matter. Serum ceruloplasmin and urine copper studies confirmed the diagnosis of WD. Zinc and D penicillamine treatment was established. Different types of facial dystonias and retrocollis were treated with BoTN-A with an appropriate protocol. Results: BoTN-A improved facial and cervical dystonia by 80% with mild side effects (blurred vision). Improvement in quality of life was ostensible. Careful visual analysis showed different types of facial dystonias including grinning facial expresion with risus sardonicus, sustained open mouth smile, dystonic dropped jaw and irregular and frequent crisis of severe blepharospasm and retrocollis. Conclusions: BoTN- A is a safe and effective treatment for the different types of facial dystonias and retrocolis associated with WD. Combination of different types of facial distonias and retrocollis should suggest WD.",patient;human;Wilson disease;dystonic disorder;motor dysfunction;Parkinson disease;cervical dystonia;blepharospasm;parkinsonism;facial expression;jaw;brain;female;safety;abnormal behavior;girl;dysarthria;focal dystonia;quality of life;cornea;ceruloplasmin blood level;white matter;liver;putamen;urine;thalamus;diagnosis;mesencephalon;basal ganglion;excretion;side effect;blurred vision;neurologic examination;copper metabolism;autosomal recessive disorder;nuclear magnetic resonance imaging;botulinum toxin A;penicillamine;zinc;copper;metal,"Ramos Burbano, G.;Echeverry, A.;Ramirez, C.;Ramos Alarcon, G.;Ramos Arevalo, A. E.;Saldana, J.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,0,
1551,Initial zinc therapy in a Wilson's disease patient with acute liver failure and copper intoxication: A clinical observation,"Objective: To evaluate whether (1) initial zinc therapy works for hepatic impairment in WD; (2) liver transplantation can be prevented by initial zinc therapy; (3) there is any correlation between normalized copper levels and clinical improvement. Background: Accumulation of copper in brain and liver has been assumed responsible for neurodegeneration and hepatic disease in WD. Thus the treatment has aimed at promoting the excretion of copper via the urine by chelators, while, since 1961, firm evidence supports the idea of normalization of copper intoxication by zinc. Methods: In an observational study on a 10-year-old girl with WD presented with acute liver failure, hemolytic anemia, and high urine copper, liver function and copper were retrospectively controlled before and after initial zinc therapy. The patient was put on 125 mg/d elemental zinc. Liver transplantation was also considered. Liver enzymes, bilirubin, and urine copper were checked at the baseline, and after 2, 4, 8, and 16 weeks on zinc therapy. Results: The patient improved biochemically and clinically in 10 days on zinc therapy, in accordance with 86% urine copper decrease. The revised WD prognostic index improved from 13 to 5, and the patient was removed from the transplant list. After 2, 4, 8 weeks on zinc therapy, AST, ALT, bilirubin, urine copper revealed constant improvements of up to 62, 226, 82, 77%, respectively by the eighth week,. The results of the second 8-week period indicated a further decrease of 25, 41, 48, 86, respectively, and 33% for serum free copper, compared to the previous results. No side effect, or clinical deterioration has been observed during the 16-week treatment period. Conclusions: The results suggest zinc as a promising, fast-acting, safe and affordable choice for the treatment of copper intoxication in WD with acute liver failure. It also supports the hypothesis of normalization of high serum free copper, which can save lives as well as a costly and risky liver transplantation, rather than stimulating the excretion of accumulated copper.",therapy;human;patient;acute liver failure;intoxication;clinical observation;motor dysfunction;Wilson disease;Parkinson disease;urine;liver transplantation;excretion;serum;transplantation;liver;hemolytic anemia;girl;brain;observational study;liver function;hypothesis;deterioration;side effect;nerve degeneration;female;liver disease;copper;zinc;bilirubin;liver enzyme;chelating agent,"Avan, A.;Kianifar, H. R.;Hoogenraad, T.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,0,
1552,Effective shift from traditional chelation therapy to evidence based zinc monotherapy in four patients with Wilson's disease and parkinsonism,"Objective: To compare clinical improvement in Wilson's disease patients (1) following normalization of high serum and urine free copper rather than excretion of copper accumulation and (2) on zinc therapy, with and without penicillamine. Background: For years the treatment of Wilson's disease has been aiming at stimulating the excretion of accumulated copper by chelating agents. However, the dilemma arises when patients paradoxically deteriorate on them. Zinc, on the other hand, is usually downplayed by being restricted to maintenance, or concomitant therapy. Chelators increase the free copper levels in serum and urine, while zinc normalizes the values by interrupting intestinal copper absorption. Methods: In a retrospective observational study on four Wilson's disease patients with parkinsonism being initially treated on penicillamine with or without zinc, we compared the subjective and objective clinical improvement before and after shifting to zinc monotherapy. Results: Three of the four patients being deteriorated on penicillamine (0.5-1 gram per day), improved significantly to a normal biochemical and clinical state on zinc (150 milligram per day). The fourth patient on penicillamine (250 milligram per day) plus zinc (200 milligram per day) improved in lower extremities during the first month, while she considerably improved on zinc monotherapy in the following months. Conclusions: The results of the four patients suggest zinc as a promising, safe and affordable treatment for patients with copper intoxication, and neurological Wilson's disease. Moreover, they support the rational idea of normalization of increased serum and urine copper values rather than stimulating the excretion of accumulated copper that induces free copper intoxication.",human;evidence based practice;parkinsonism;chelation therapy;monotherapy;motor dysfunction;patient;Wilson disease;Parkinson disease;excretion;serum;urine;intoxication;therapy;leg;health status;observational study;absorption;zinc;copper;penicillamine;chelating agent,"Avan, A.;Azarpazhooh, M. R.;Hoogenraad, T. U.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,1,
1553,Current status of Wilson disease: Does early treatment protect from nervous system impairment?,"Objective: Aim of this study is to assess the impact on nervous system of Wilson disease (WD) in early treated (ET) patients with long duration of disease. Background: During the course of WD neurological disorders (ND) have been described frequently especially when treatment is delayed. In the last years most of WD cases have been diagnosed in childhood at the occurrence of hypertransaminasemia (HT) receiving an early treatment and apparently not showing a progression of the disease afterwards. Methods: A clinical, neurophysiologycal and neuroradiological assessment has been conducted in patients with WD with long duration of disease and therapy. Clinical neurological evaluation was performed using the neurological section of ""global assessment scale"" (GAS) for WD. Transcranial magnetic stimulation (TMS) was performed to study the central conduction time and cortical excitability with the paired pulse technique exploring short interval cortical inhibition and intracortical facilitation. A brain MRI scan was performed for each patient. Results: 27 patients (16 M, age range 13-47 y) with a mean disease duration of 16.5 years (range 7-28) have been assessed from 2011 to 2012. All patients started treatment soon after the diagnosis and currently are on pennicillamine (6 patients) or zinc acetate (21 patients). TMS and brain MRI studies were normal in 23 subjects who received diagnosis of WD for the occurrence of HT in childhood and never reported ND. The remaining 4 patients were diagnosed in adolescence presenting ND as onset, only 2 of them still show neurological signs (GAS 16-18) but all have brain MRI alterations while TMS findings are normal. Conclusions: During the recent decades WD natural history seems to be changed as nervous system could be not affected when patients are diagnosed in childhood receiving early treatment (Ala A 2007). Our study confirms that ET patients, not presenting ND at the onset, do not show neurological clinical signs even after a long disease duration. The normality of TMS and brain MRI studies also suggests the absence of sublicnical nervous system impairment.",Wilson disease;nervous system;motor dysfunction;Parkinson disease;human;patient;brain;childhood;diagnosis;disease duration;nuclear magnetic resonance imaging;neurologic disease;gas;adolescence;hypertransaminasemia;pulse rate;excitability;transcranial magnetic stimulation;therapy;history;zinc acetate,"Esposito, M.;Dubbioso, R.;Manganelli, F.;Ranucci, G.;Didato, F.;Matarazzo, M.;Iorio, R.;Santoro, L.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,1,
1554,Levodopa-responsive Parkinsonism and small fiber dysfunction in patients with Wilson's disease,"Objective: To describe a series of patients with Wilson's disease (WD) associated with levodopa-responsive parkinsonism and autonomic dysfunction. Background: Patients with WD present or develop during their disease course a wide variety of neuropsychiatric symptoms. Few reports have described autonomic dysfunction in WD patients. Methods: Chart review of 4 patients with WD who were evaluated for the presence of neuromuscular dysfunction and had waterinduced skin wrinkling test (Teoh, JNNP 2008;79:835). This study was approved by the local institutional IRB. Results: Patient 1: A 37 yoF presented with cirrhosis at age 33 was diagnosed with WD and treated with ZnSO4, penicillamine and piridoxine/complex B vitamins. Since age 35 she developed pramipexole and levodopa-responsive parkinsonism, burning and numbness in arms and genital area and urinary incontinence. NCS/EMG was normal but water-induced skin wrinkling test (SWT) revealed small fiber dysfunction (mean 4-digit wrinkling of 1). Patient 2: A 23 yoM was diagnosed with WD at age 14 and has been treated with penicillamine and piridoxine since then. Since age 21, he developed levodopa-responsive parkinsonism, with resting tremor, weight loss, dysphagia and dysphonia. NCS/EMG was normal but water-induced SWT was abnormal (mean 4-digit wrinkling of 0.25). Patient 3: A 34 yoW presented with psychosis and marked behavioral dysfunction followed by levodopa-responsive parkinsonism and episodes of loss of consciousness. He has family history of WD and was treated with penicillamine and complex B vitamins. NCS/EMG and water-induced SWT were normal (mean 4-digit wrinkling of 4). Patient 4: A 38 yoF presented with liver dysfunction, behavior changes and parkinsonism (resting tremor in the upper extremities and akinetic-rigid state) at age 24 and was diagnosed with WD. She was treated with penicillamine and biperiden. Parkinsonism almost completely subsided after treatment with penicillamine. Waterinduced SWT was normal (mean 4-digit wrinkling of 3.6). Conclusions: A subset of WD patients with levodopa-responsive parkinsonism also exhibit abnormalities on skin wrinkling test (autonomic dysfunction).",human;patient;parkinsonism;motor dysfunction;fiber;Wilson disease;Parkinson disease;wrinkle;autonomic dysfunction;skin;arm;tremor;neuromuscular disease;urine incontinence;disease course;paresthesia;behavior change;liver dysfunction;family history;consciousness;psychosis;dysphonia;dysphagia;weight reduction;liver cirrhosis;medical record review;levodopa;penicillamine;water;vitamin;pramipexole;biperiden;pyridoxine,"Gondim, F. A.;Araujo, D. F.;Oliveira, I. S.;Melo, A. P.;Alves, L. C.;Araujo, I. T.;Vale, O. C.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,0,
1555,Alterations of cortical excitability and central motor conduction time in patients with Wilson's disease,"Objective: To determine the cortical excitability changes in patients with WD by measuring the cortical resting motor threshold (RMT) and Central Motor Conduction Time (CMCT) using transcranial magnetic stimulation (TMS). Background: Wilson's disease (WD), an autosomal recessive disorder of copper metabolism, leads to widespread structural alterations of central nervous system. However, little is known about the neuronal dysfunction in this disorder. Methods: The subjects of this study were 13 patients (10 male and 3 female) with WD diagnosed by presence of Kayser-Fleischer and biochemical parameters. TMS was performed using a figure-ofeight coil attached to Magstim 200 stimulator. Motor evoked potentials (MEP) were recorded from right first dorsal interosseous (FDI) at rest. RMT was determined using standard techniques and the CMCT by 'F' wave method. Comparison was made with data from 26 healthy controls. Results: The mean age of the patients was 19.5 +/- 9.5 years, the mean age of onset of symptoms was 16.5 +/- 10.7 years and the mean duration of illness was 2.8 +/- 2.5 years. Of the 13 patients, 11 patients were on treatment with zinc sulphate and/or penicillamine and two patients were not on any medications. Dysarthria was the presenting symptom in five patients (38.5%). Chorea, tremors, dystonia and abnormal gait were the presenting symptoms in two patients (15.4%) each. RMT was recordable in 10 patients and not recordable in three patients. Compared to controls, the patients with WD in whom RMT was recordable, had significantly higher mean RMT as well as CMCT (RMT: 80.9 +/- 14.8vs.41.1 +/- 7, p < 0.0001; CMCT: 6.7 +/- 0.5 ms vs. 4.8 +/- 0.6 ms; p < 0.0001). The duration of illness of the three patients in whom RMT was not recordable was 4, 2 and 1 years. In two of these three patients, a MEP could be obtained with active contraction of the right FDI. The CMCT in these two patients was also prolonged (8.8ms and 5.6ms). Conclusions: Patients with WD have reduced cortical excitability and prolonged central motor conduction time which may be due to the intracortical presynaptic motor disturbance. Follow up studies are required to determine whether these changes are reversible with decoppering treatment.",excitability;human;patient;motor dysfunction;Parkinson disease;Wilson disease;diseases;parameters;central nervous system;drug therapy;evoked muscle response;male;onset age;female;autosomal recessive disorder;transcranial magnetic stimulation;dystonia;dysarthria;chorea;tremor;gait disorder;follow up;copper metabolism;penicillamine;zinc sulfate,"Jhunjhunwala, K. R.;Prashant, D. K.;Pal, P. K.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,0,
1556,A case of Wilson's disease with lid-opening apraxia treated with botulinum toxin,"Objective: To describe the response to botulinum toxin injection in a case of severe neuropsychiatric Wilson's disease with lidopening apraxia. Background: Ocular findings such as Kayser-Fleischer rings and sunflower cataracts are well known to be associated with Wilson's disease. Other ocular findings have been reported and are sometimes thought to be coincidental. To our knowledge, lid-opening apraxia has been described only once by JR Keane in 1988. There is no case report of lid-opening apraxia treated by botulinum injection in Wilson's disease. Methods: The patient experienced a worsening of his neurological condition following the initiation of d-penicillamine with the development of lid-opening apraxia. He used sensory tricks to open his eyes. He was almost functionally blind and needed help to walk because of his eye closure. No weakness or ptosis was detectable on examination. We injected onabotulinumtoxinA in upper and lower eyelids bilaterally in the pretarsal portion of the orbicularis oculi muscles. The ocular findings also indicated Kayser-Fleischer rings, sunflower cataracts, ocular flutter and square wave jerks. Results: Two days after the injection, the patient noticed a dramatic improvement in his condition with significant improvement in his quality of life. No side effects were reported. Conclusions: This is the second case of lid-opening apraxia in Wilson's disease and the first reported response to botulinum toxin injection. Our findings also reinforce the idea that lid-opening apraxia is a pretarsal dystonia with the presence of sensory tricks, the association with lower face dystonia (risus sardonicus) and the response to botulinum toxin injection.",apraxia;motor dysfunction;Parkinson disease;Wilson disease;injection;human;patient;dystonia;sunflower;cataract;ocular flutter;orbicularis oculi muscle;lower eyelid;quality of life;side effect;examination;ptosis;case report;eyelid closure;eye;weakness;botulinum toxin;penicillamine;botulinum toxin A,"Dufresne, A. M.;Chouinard, S.;Boghen, D.",2013,June,http://dx.doi.org/10.1002/mds.25605,0,0,
1557,The brain metals accumulation in wilson's disease,"OBJECTIVE: The aim of this study was to evaluate concentration of copper, iron, zinc and manganese in WD brain autopsy tissues and their association with WD phenotypic presentation. BACKGROUND: Wilson's Disease (WD) is an inherited copper metabolism disorder with pathological copper tissue accumulation, mainly in liver and brain. Previous studies have shown that accumulation of other metals in the brain tissue occurs in numerous neurodegenerative disorders. However, until now this issue have not been quantitatively examined in WD. DESIGN/METHODS: The study material consisted of 17 brains (12 WD patients, 5 controls) obtained upon autopsy. Samples were taken from 4 different regions of each brain: frontal cortex, putamen, nucleus dentatus and pons. The copper, manganese and zinc levels were assessed using plasma mass spectrometry. Iron concentration was measured with atomic absorption spectroscopy. Clinical presentation of WD was considered hepatic or neuropsychiatric. RESULTS: Copper content was homogenously increased in all investigated structures of WD brains compared to controls (41.0+/-18.6 vs. 5.4+/-1.8 mg/g, p<0.01). Concentrations of manganese and zinc in WD brains were similar to the controls, and did not differ between analyzed brains parts. However, the concentration of iron in nucleus dentatus was significantly higher in WD brains (56.8+/-14.1 vs. 32.6+/-6.0 ug/g, p<0.05). There were no associations between the concentration of any metal in any part of brain and the clinical presentation of WD. CONCLUSIONS: According to our findings, in the course of WD copper accumulate in different parts of the brain irrespectively of predominant phenotypic presentation. Zinc and manganese does not seem to be involved in the pathology. However, increased amounts of iron appear to accumulate in nucleus dentatus. We speculate that this effect may be due to diminished level of ceruloplasmin, but further studies are needed.",neurology;brain;Wilson disease;dentate nucleus;autopsy;brain tissue;pons;liver;plasma;atomic absorption spectrometry;bioaccumulation;frontal cortex;metabolic disorder;putamen;human;mass spectrometry;pathology;patient;diseases;copper metabolism;tissues;metal;copper;manganese;iron;zinc;ceruloplasmin,"Czlonkowska, A.;Litwin, T.;Gromadzka, G.;Szpak, G.;Bulska, E.",2013,,,0,0,
1558,Therapeutic efficacy of D-penicillamine encapsulated alginate/chitosan nanoparticles in rat model of copper toxicity with neurobehavioral impairments,"Animal models of Wilson's disease (WD) viz. Long evans cinnamon rats, rarely exhibit neurological symptoms impeding the development of novel therapeutic approaches to treat neurological manifestations in WD patients. The aim of this study was to 1. examine the effect of intraperitoneally injected copper lactate for 90 days especially on copper and zinc levels in liver, kidney & brain tissues; expression of hepatic metallothionein-I (MT-I) and Atp7b gene; and MT-III and acetylcholine esterase (AChE) gene in brain, biochemical parameters, and neurobehavioral functions of male Wistar rats, and 2. therapeutic evaluation of orally administered D-penicillamine encapsulated alginate/chitosan nanoparticles for 90 days on Cu intoxicated Wistar rats. Reverse transcription-PCR and Morris water maze test were used for expression and neurobehavioral studies. Copper intoxicated animals showed significantly increased ceruloplasmin, serum & urine copper levels and decreased serum acetyl choline esterase (AChE) activity, increased expression of hepatic MT-I gene with impaired neuromuscular coordination and spatial memory. However, no changes were observed on the expression levels of hepatic Atp7b gene; and MT-III and AChE gene in brain. Cu intoxicated rats revealed a significant increase in the liver, brain and kidney tissues copper content (99.1, 73 and 74.9% increase respectively), decreased liver zinc (40% decrease) & interestingly, increased brain zinc content (77.1% increase) compared to controls rats. Histopathological studies demonstrated grade 4 copper depositions in the liver and grade 1 copper associated protein in liver tissues of test rats by rhodanine and orcein stains respectively. Astrocytes swelling were observed in cerebral cortex sections of brain tissues of Cu intoxicated rats. D-penicillamine encapsulated alginate/chitosan nanoparticles therapy resulted in significant reduction of liver and brain Cu content, serum ceruloplasmin level & increase in serum AChE activity with improvement in neurological functions. In conclusion, chronic copper toxicity may lead to increased copper content in liver & brain, increased hepatic MT-I gene expression, ceruloplasmin levels and, neurobehavioral impairments may be by interfering in acetylcholine modulated neurotransmission; however, D-penicillamine encapsulated nanoparticles may reverse impairments caused by chronic Cu intoxication to a significant extent in Wistar rats.",liver;rat;animal model;toxicity;therapy;brain;gene;Wistar rat;serum;brain tissue;male;swelling;parameters;astrocyte;stain;histopathology;spatial memory;Long Evans cinnamon rat;urine;kidney;maze test;human;kidney parenchyma;reverse transcription polymerase chain reaction;neurologic disease;neurotransmission;brain cortex;ceruloplasmin blood level;gene expression;intoxication;patient;Wilson disease;penicillamine;nanoparticle;copper;zinc;ceruloplasmin;acetylcholine;rhodanine;acetylcholinesterase;protein;cholinesterase;metallothionein I;water,"Pal, A.;Badyal, R.;Vasishta, R. K.;Prasad, R.",2013,April,http://dx.doi.org/10.1016/S0168-8278%2813%2961395-1,0,0,
1559,Wilson's disease in children: The rate of liver cirrhosis,"Introduction: Initial manifestation of WD is variable and is rarely detected in children under 5 years of age, in most cases manifesting with abnormal liver function. Aim: To determine the rate of liver cirrhosis in children with WD. Materials and Methods: 101 children (boys - 50; girls - 51; mean age 12.3+/-2.9 years). The diagnosis of WD was supported by decreased serum ceruloplasmin (SC), increased copper urinary excretion: basal (Cu0) and after D-penicillamine challenge (Cu1), the presence of Kaiser-Fleischer rings (KF), increased liver copper content and genetic analisis. Cirrhosis is diagnosed based on morphological data or complex laboratory and instrumental investigations. Results: At initial diagnosis of WD liver cirrhosis was established in 44 (43.6%) children aged 13.3+/-2.1 years: in children under the age of 12 years - in 14 (31.1%), over 12 years - even in 30 (53.6%) patients (p < 0.05). In children with liver cirrhosis were significantly (p < 0.05) more often noted the presence of extrapyramidal neurologic symptoms - 36.4% of cases, the presence of KF - in 68.2% children, acute Coombs-negative hemolytic anemia (HA) - in 20.5% children, compared with patients with WD in the absence of cirrhotic liver transformation (n = 57), in which the rate of neurological symptoms was - 10.5%, the presence of KF - 24.6%, the presence of HA - 3.5% children. In children with WD at the stage of liver cirrhosis: Cu0 189.5 [111.1; 492.9] mcg/24h, Cu1 2015.5+/-1206.7 mcg/24h, which significantly exceeds that in children with WD in the absence of liver cirrhosis: Cu0 100.8 [74.7, 133.0] mcg/24h, Cu1 1529.0+/-866.9 mcg/24h (p < 0.05). SC does not depend on the stage of WD: in liver cirrhosis SC was 9.1+/-5.2 mg/dl, and in its absence - 11.3+/-7.6 mg/dl (p > 0.05). Conclusion: In pediatric practice there is late diagnosis of WD, which leads to the diagnosis of the disease in 43.6% at the stage of liver cirrhosis. Liver cirrhosis in children with WD is associated with the presence of KF (68.2%), neurological symptoms (36.4%) and higher levels of copper urinary excretion.",liver;child;liver cirrhosis;human;diagnosis;neurologic disease;urinary excretion;patient;male;boy;liver function;hemolytic anemia;laboratory;ceruloplasmin blood level;girl;female;pediatrics;copper;penicillamine,"Chetkina, T.;Potapov, A.;Varichkina, M.;Pakhomovskaya, N.;Senyakovitch, V.;Tumanova, E.;Karagulian, N.",2013,April,http://dx.doi.org/10.1016/S0168-8278%2813%2961384-7,0,0,
1560,Acute hemolytic anemia as an initial presentation of wilson's disease in children,"Background: Background: Wilson's disease (WD) is an inherited disorder of copper metabolism. Hemolytic anemia (HA) in WD occurs in up to 17% of patients at some point during their illness. Objectives: Objective: Our aim was to screen forWD among children presenting with HA. Design/Method: Methodology: 20 cases (mean age 8.8+/-3.9 years) with Coombs negative HA attending the hematology clinic of children hospital, Cairo University were screened for WD by serum ceruloplasmin level, 24-h urinary copper before and after D-pencillamine challenge test (PCT) and slit lamp examination for detecting Kayser- Fleisher. Results: Results: No case had low ceruloplasmin while bilateral Kayser Fleisher rings was detected in 5% of our cases. Urinary copper was elevated in 5% before and in 40% after PCT. According to the scoring system used, one case had definite WD and 7 cases were likely to have WD. These 8 (40%) cases were referred to as group B and were compared to the rest of the patients (group A). Group B had a significantly lower hemoglobin, MCVand MCH and retics (p=0.04, 0.001, 0.04 and 0.04) respectively and a significantly higher urinary copper after penicillamine (p=0.000) when compared to group A (unlikely Wilson). Conclusion: Conclusion: WD is not uncommon in children with hemolytic anemia after exclusion of common causes.",human;hemolytic anemia;society;child;Wilson disease;diseases;patient;provocation test;ceruloplasmin blood level;university;pediatric hospital;scoring system;hospital;hematology;methodology;slit lamp;copper metabolism;copper;penicillamine;ceruloplasmin;hemoglobin,"Hamdy, M.;El Raziky, M.;El Shahawy, A.",2013,June,http://dx.doi.org/10.1002/pbc.24509,0,0,
1561,Orphan drugs and rare diseases in Andorra,"Background and objective: To establish the prevalence of rare diseases (RD) in treatment with orphan drugs (OD) and its economic impact in the pharmaceutical budget (PB). Setting and method: Retrospective, observational study, over a 1-year period (01-05-2011 to 01-05-2012), of patients diagnosed with RD in treatment with OD in Andorra. Estimated population is about 80,000 people and this country has only one hospital, Data were obtained from 1. Data records of inpatients/outpatients pharmacy software (Farmatools ) to identify OD dispensed by hospital pharmacy department and to obtain variables related to Drugs use in units and cost in euros. 2. Sales report of OD imported by the international wholesealer during studying period. OD requests by community pharmacies were included. 3. Orphanet web page to stablish variables: Relationship OD/RD indication and estimated prevalence of RD in Europe (reviewed May 2012). We include OD that received a European marketing authorisation. Triemtine has also been included because it has an orphan designation status. Main outcome measures: Type of OD, Type of RD, number of patients diagnosed and treated, OD's cost (euros), anual budget of Pharmacy Hospital drugs (euros). Results: 18 patients were identified in treatment with OD for RD, 50 % male, 67 % adults (range 14-64 year-old) and 33 % elderly (>65 yearold.). General prevalence was 18/80,000 (equivalent to 22.5/100,000), with 8 different RD and a patient/RD ratio 2.25 (range 1-5). Specific prevalences were: pulmonary arterial hypertension: 5/80,000, systemic sclerosis and multiple myeloma: 3/80,000, Wilson's disease and chronic myeloid leukaemia: 2/80,000, medullary thyroid carcinoma, idiopathic pulmonary fibrosis and myelodisplastic syndrome: 1/80,000. OD indication has not been accomplished in two cases: aerosolized tobramycin in the treatment of bronchiectasis with chronic pulmonary infection due to Pseudomonas aeruginosa without cystic fibrosis (2 patients) and sorafenib for the treatment of medullary thyroid carcinoma (1 patient). OD distribution (number of patients): bosentan (6), aerosolized tobramycin (2), imatinib mesilate (2), lenalidomide (2), sildenafil citrate (2), Trientine (1), zinc acetate dihydrate (1), azacitidine (1), pirfenidone (1), sorafenib, thalidomide (1), intravenous ibuprofen (0). Economic impact ofODin the pharmaceutical Hospital budget in the study period was 8.2 %. Of this 8.2, 16.5 % refers to off-label OD use. OD economic distribution based on ATC category was: A: 2.1 %, C: 29.7 %, G: 0.7 %, J: 4.1 %, L: 63.4 %. Conclusions: - The prevalence of RD treated with OD in Andorra was 18/80,000 - Economic impact of OD in Hospital Pharmacy budget during the study period was 8.2 % - Pulmonary arterial hypertension is the more prevalent RD in Andorra.",rare disease;Andorra;clinical pharmacy;therapy;human;patient;prevalence;budget;pharmacy;hospital;thyroid medullary carcinoma;pulmonary hypertension;hospital pharmacy;systemic sclerosis;lung infection;bronchiectasis;population;aged;fibrosing alveolitis;marketing;adult;male;Europe;observational study;chronic myeloid leukemia;Pseudomonas aeruginosa;cystic fibrosis;community;computer program;multiple myeloma;Wilson disease;orphan drug;sorafenib;tobramycin;azacitidine;zinc acetate;trientine;pirfenidone;thalidomide;ibuprofen;sildenafil;lenalidomide;imatinib;bosentan,"Gea, E.;Gil, E.;Barral, N.;Gonzalez, V.;Soler, A.;Avellanet, M.",2013,October,http://dx.doi.org/10.1007/s11096-013-9801-0,0,0,
1562,Hepatocellular carcinoma in a case of Wilson's disease,"Objective: Hepatocellular carcinoma and other tumors of the liver are extremely rare inWilson's disease.We report a case of 41-year-old patient who presented with a hepatocellular carcinoma associated with Wilson's disease. The patient was diagnosed to have Wilson's disease at age of 16 years. He came to the hospital at age of 41 years with abdominal pain, and radiographic evidence of right hepatic lobe mass, with the presence of multiple pulmonary nodules. The patient died 7 days after admission. We conclude that patients withWilson's disease should be considered at risk of hepatocellular carcinoma.Aliver imaging and alfa-fetoprotien level should be included in the follow-up of patients with Wilson's disease. Methods: In this paper we describe the case of a young patient who have Wilson's disease associated with HCC, who was diagnosed with HCC after 25 years of penicillamine and zinc treatment. Results: Wilson's disease is a hepatolinticular degeneration that results from mutation in ATP7B gene, that responsible for production of protein important for copper transport and elimination of excess free copper from body. D-Penicillamine contains a free sulfhydryl group that functions as a copper chelating moiety. Its major effect is to promote urinary excretion of copper and reduces the affinity of proteins for copper. Oral zinc interferes with the absorption of copper, it induces metallothionein (an endogenous chelator of metals) in enterocytes, which has a greater affinity for copper than for zinc, causing it to bind luminal copper and thereby preventing its entry into the circulation [7, 8]. It is assumed that hepatic copper has a protective effect against malignant transformation [9, 10]. Some studies have found that copper may prevent the occurrence of HCC [11, 12]. However, patients with long-standing Wilson's disease who are maintained on D-penicillamine have more risk to develop HCC. On the other hand, Patients with Wilson disease require lifelong therapy. Discontinuation of therapy can lead to the development of acute failure. In this case report long disease period with pinicillamine therapy played a role in the presence of HCC. Whether copper enhances or reduces the risk for HCC has yet to be determined [13].Avariety of important risk factors for the development of hepatocellular carcinoma (HCC) have been identified and they have a well known effect in developing HCC. These include the hepatitis B carrier state, chronic hepatitis C virus (HCV) infection, hereditary hemochromatosis, and cirrhosis of almost any cause [14]. While, development of HCC in patients withWilson disease is extremely rare. In conclusion, a periodic follow up of Wilsons disease patients with periodic checkup of alfafetopritien level and abdominal US is recommended in order to discover the HCC earlier and they can benefit from other modality of treatment of HCC i.e. surgical resection, Radiofrequency ablation, Transarterial chemoembolization, or other modality that might be indicated. Possible consideration of inclusion in a transplant program can benefit the patients in some cases. Conclusion: In conclusion, a periodic follow up of Wilsons disease patients with periodic checkup of alfa-fetopritien level and abdominal US is recommended in order to discover the HCC earlier and they can benefit from other modality of treatment of HCC i.e. surgical resection, Radiofrequency ablation, Transarterial chemoembolization, or other modality that might be indicated. Possible consideration of inclusion in a transplant program can benefit the patients in some cases.",Wilson's disease;hcc;Follow-up;follow up;liver cell carcinoma;Asian;gastroenterology;human;patient;Wilson disease;risk;therapy;radiofrequency ablation;periodic medical examination;surgery;chemoembolization;transplantation;hepatitis B;risk factor;case report;malignant transformation;imaging;multiple pulmonary nodules;abdominal pain;intestine cell;liver;liver cirrhosis;absorption;hospital;neoplasm;Hepatitis C virus;hepatitis C;urinary excretion;hemochromatosis;gene;mutation;heterozygote;degeneration;virus infection;copper;penicillamine;zinc;protein;metal;chelating agent;metallothionein;thiol group,"Hamid, N.;Zakary, N.",2013,October,http://dx.doi.org/10.1111/jgh.12363_2,0,0,
1563,Metal transport and homeostasis within the human body: Toxicity associated with transport abnormalities,"In this work, latest reports about metal toxicity, transport and homeostasis have been thoroughly described and discussed. Although diseases associated with transport and homeostasis abnormalities are those of great interest, still a variety of the phenomena associated with these processes are under debate. In this paper, we try to summarize the newest theses on this topic, presenting contradictory points of view. We focus on toxic and essential metal pathways crossing and try to follow the exact metal binding molecules within the body and provide insight into the transport mechanism. Special attention is given to the mechanism of action of lately investigated metal transporters. © 2012 Bentham Science Publishers.",Metal homeostasis;Toxicity;Transport;Alzheimer disease;amyotrophic lateral sclerosis;article;blood brain barrier;bronchitis;cancer risk;cell degeneration;cell division;cell population;chelation therapy;chronic liver failure;dermatitis;dialysis;dialysis encephalopathy;DNA damage;DNA repair;Down syndrome;drug megadose;dystonia;eczema;eukaryotic cell;follow up;glia cell;homeostasis;human;hypokinesia;Indian childhood cirrhosis;iron deficiency anemia;iron overload;iron transport;ischemia;leukopenia;lung cancer;lymphadenopathy;membrane transport;Menkes syndrome;metal binding;neutropenia;non insulin dependent diabetes mellitus;nonhuman;nose cancer;nuclear magnetic resonance imaging;oxidative stress;pancreas islet beta cell;Parkinson disease;prokaryotic cell;restless legs syndrome;rigidity;sideroblastic anemia;substantia nigra pars compacta;total parenteral nutrition;tremor;vascular disease/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];X chromosome linked disorder;albumin;aluminum/to [Drug Toxicity];arsenic/to [Drug Toxicity];cadmium/to [Drug Toxicity];chromium/dt [Drug Therapy];chromium/to [Drug Toxicity];chromium/pd [Pharmacology];chromium derivative/do [Drug Dose];copper/to [Drug Toxicity];cotransporter;iron/to [Drug Toxicity];manganese/to [Drug Toxicity];metallothionein I/ec [Endogenous Compound];metallothionein II/ec [Endogenous Compound];metallothionein III/ec [Endogenous Compound];methylcyclopentadienylmanganese tricarbonyl;neuromelanin/ec [Endogenous Compound];nickel/to [Drug Toxicity];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid;zinc/to [Drug Toxicity];zinc transporter/ec [Endogenous Compound],"Potocki, S.;Rowinska-Zyrek, M.;Witkowska, D.;Pyrkosz, M.;Szebesczyk, A.;Krzywoszynska, K.;Kozlowski, H.",2012,June,,0,0,
1564,Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: A new treatable disorder,"Background: The first gene causing early-onset generalized dystonia with brain manganese accumulation has recently been identified. Mutations in the SLC30A10 gene, encoding a manganese transporter, cause a syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia. Methods: We present 10-year longitudinal clinical features, MRI data, and treatment response to chelation therapy of the originally described patient with a proven homozygous mutation in SLC30A10. Results: The patient presented with early-onset generalized dystonia and mild hyperbilirubinemia accompanied by elevated whole-blood manganese levels. T1-sequences in MRI showed hyperintensities in the basal ganglia and cerebellum, characteristic of manganese deposition. Treatment with intravenous disodium calcium edetate led to clinical improvement and reduction of hyperintensities in brain imaging. Conclusions: We wish to highlight this rare disorder, which, together with Wilson's disease, is the only potentially treatable inherited metal storage disorder to date, that otherwise can be fatal as a result of complications of cirrhosis. © 2012 Movement Disorder Society.",Cirrhosis;Dystonia;Hypermanganesemia;Polycythemia;slc30a10;add on therapy;adult;article;basal ganglion;bioaccumulation;blood level;bradykinesia;case report;cerebellum;chelation therapy;clinical feature;dystonia/dt [Drug Therapy];female;gene;gene mutation;homozygosity;human;human tissue;hyperbilirubinemia/dt [Drug Therapy];nuclear magnetic resonance imaging;priority journal;SLC30A10 gene;spasticity;treatment response;walking difficulty;Wilson disease;alpha tocopherol;edetate calcium disodium/cb [Drug Combination];edetate calcium disodium/dt [Drug Therapy];edetate calcium disodium/iv [Intravenous Drug Administration];ferrous fumarate/cb [Drug Combination];ferrous fumarate/po [Oral Drug Administration];levodopa/dt [Drug Therapy];manganese/ec [Endogenous Compound];penicillamine/po [Oral Drug Administration],"Stamelou, M.;Tuschl, K.;Chong, W. K.;Burroughs, A. K.;Mills, P. B.;Bhatia, K. P.;Clayton, P. T.",2012,01 Sep,http://dx.doi.org/10.1002/mds.25138,0,0,
1565,Idiopathic thrombocytopenia and neurologic manifestations in a young female leading to the diagnosis of Wilson's disease,"We present a 19-year-old patient with hematologic and neurologic manifestations associated with Wilson's disease. Idiopathic thrombocytopenia was diagnosed in October 2009. Bone marrow aspiration was normal. Gradually her neurologic and psychiatric symptoms emerged, dysarthria, writing apraxia, learning difficulties, emotionalism and eventually dystonia of hands. The serum ceruloplasmin was low, and the Kayser Fleischer's ring was positive. MRI of the brain showed abnormality in the bilateral basal ganglia, brain stem and superior cerebellar peduncles without post-contrast enhancement. Declaration of interest: None Citation: Zaheryany SMS, Bidaki R, Hemmatian Brujeni N, Rezvani M, Hakim Shooshtari M, Idiopathic thrombocytopenia and neurologic manifestations in a young female leading to the diagnosis of Wilson's disease. Iran J Psychiatry Behav Sci 2012; 6(2): 96-99.",Apraxia;Kayser fleischer's ring;Thrombocytopenia;Wilson's disease;adult;antibiotic therapy;article;basal ganglion;bone marrow biopsy;brain;brain stem;case report;ceruloplasmin blood level;dysarthria;dystonia;eye movement;female;human;human tissue;learning disorder;Mini Mental State Examination;neurologic disease;nuclear magnetic resonance imaging;splenomegaly;superior cerebellar peduncle;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];antibiotic agent;ceruloplasmin/ec [Endogenous Compound];penicillamine;prednisolone/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Zaheryany, S. M. S.;Bidaki, R.;Brujeni, N. H.;Rezvani, M.;Shooshtari, M. H.",2012,,,0,0,
1566,Catatonia: A rare presenting symptom of Wilson's disease,,adult;case report;catatonia/dt [Drug Therapy];catatonia/th [Therapy];cognitive defect;depression;drug dose increase;electroconvulsive therapy;human;letter;male;mood disorder;personality disorder;priority journal;psychosis;rare disease;schizophrenia;Wilson disease/dt [Drug Therapy];lorazepam/dt [Drug Therapy];lorazepam/po [Oral Drug Administration];olanzapine/do [Drug Dose];olanzapine/dt [Drug Therapy];olanzapine/po [Oral Drug Administration];quetiapine/do [Drug Dose];quetiapine/dt [Drug Therapy];trifluoperazine/dt [Drug Therapy];trifluoperazine/po [Oral Drug Administration];trihexyphenidyl/dt [Drug Therapy];trihexyphenidyl/po [Oral Drug Administration];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Nayak, R. B.;Shetageri, V. N.;Bhogale, G. S.;Patil, N. M.;Chate, S. S.;Chattopadhyay, S.",2012,,,0,0,
1567,The molecular basis of memory,"We propose a tripartite biochemical mechanism for memory. Three physiologic components are involved, namely, the neuron (individual and circuit), the surrounding neural extracellular matrix, and the various trace metals distributed within the matrix. The binding of a metal cation affects a corresponding nanostructure (shrinking, twisting, expansion) and dielectric sensibility of the chelating node (address) within the matrix lattice, sensed by the neuron. The neural extracellular matrix serves as an electro-elastic lattice, wherein neurons manipulate multiple trace metals (n > 10) to encode, store, and decode coginive information. The proposed mechanism explains brains low energy requirements and high rates of storage capacity described in multiples of Avogadro number (N<inf>A</inf> = 6 x 10<sup>23</sup>). Supportive evidence correlates memory loss to trace metal toxicity or deficiency, or breakdown in the delivery/transport of metals to the matrix, or its degradation. Inherited diseases revolving around dysfunctional trace metal metabolism and memory dysfunction, include Alzheimer's disease (Al, Zn, Fe), Wilson's disease (Cu), thalassemia (Fe), and autism (metallothionein). The tripartite mechanism points to the electro-elastic interactions of neurons with trace metals distributed within the neural extracellular matrix, as the molecular underpinning of ""synaptic plasticity"" affecting short-term memory, long-term memory, and forgetting. © 2012 American Chemical Society.",Alzheimer disease;amnesia;autism;brain level;chemical bond;cognition;computer memory;extracellular matrix;human;information processing;long term memory;memory;metal binding;metal metabolism;nerve cell;nerve cell plasticity;neurobiology;priority journal;review;short term memory;thalassemia;Wilson disease;chondroitin sulfate;glycosaminoglycan;heparan sulfate;hyaluronic acid;metal ion;proteoglycan;trace metal,"Marx, G.;Gilon, C.",2012,15 Aug,http://dx.doi.org/10.1021/cn300097b,0,0,
1568,Neurotoxicology: Five new things,"Neurotoxic disease can mimicmany common neurologic disease states, including parkinsonism, myelopathy, neuropathy, and encephalopathy. Accurate diagnosis and appropriate treatment may result in a favorable outcome. This review highlights 5 areas of neurotoxicology for which there is an emerging understanding of disease processes or patterns of exposure, including 3 specific metal toxicities (manganism, zinc-induced copper deficiency, and cobaltchromium neuropathy). Toxin-induced posterior reversible encephalopathy syndrome is more widely recognized and reported in association with an evergrowing list of drugs. Two new categories of street drugs, synthetic cathinones and cannabinoids, have been identified as public health threats due to their popularity, availability, and severity of toxicity. Copyright © 2012 American Academy of Neurology.",acne/dt [Drug Therapy];acrodermatitis enteropathica/dt [Drug Therapy];aggressiveness;agitation;amnesia;anemia;anxiety disorder/dt [Drug Therapy];behavior disorder/dt [Drug Therapy];brain hemorrhage/co [Complication];bruxism;cardiomyopathy/co [Complication];celiac disease/dt [Drug Therapy];clinical feature;common cold/dt [Drug Therapy];common cold/pc [Prevention];cooling;copper deficiency;decubitus/dt [Drug Therapy];delusion;diaphoresis;diarrhea/dt [Drug Therapy];disease severity;dizziness;drug abuse;dystonia;extrapyramidal syndrome/co [Complication];glucagonoma/dt [Drug Therapy];headache;health care personnel;hearing impairment/co [Complication];hepatic encephalopathy/dt [Drug Therapy];human;hyperactivity/dt [Drug Therapy];hyperreflexia;hypertension/dt [Drug Therapy];hyperthermia/th [Therapy];hypokalemia;hypothyroidism/co [Complication];medical history;memory disorder/dt [Drug Therapy];mental instability;mydriasis;myocarditis/dt [Drug Therapy];myoclonus;myoclonus epilepsy/dt [Drug Therapy];neurotoxicology;neutropenia;nuclear magnetic resonance imaging;occlusive cerebrovascular disease/co [Complication];paranoia;peripheral neuropathy/co [Complication];physical examination;posterior reversible encephalopathy syndrome/si [Side Effect];priority journal;psychosis/dt [Drug Therapy];review;seizure/dt [Drug Therapy];sickle cell anemia/dt [Drug Therapy];sinusitis/dt [Drug Therapy];sinusitis/pc [Prevention];tachycardia/dt [Drug Therapy];trace metal blood level;tremor;vasospasm/co [Complication];visual impairment/co [Complication];Wilson disease/dt [Drug Therapy];benzodiazepine derivative/dt [Drug Therapy];bevacizumab/ae [Adverse Drug Reaction];cannabinoid/to [Drug Toxicity];cathinone/to [Drug Toxicity];cisplatin/ae [Adverse Drug Reaction];cyclophosphamide/ae [Adverse Drug Reaction];cyclosporin/ae [Adverse Drug Reaction];cyproheptadine/dt [Drug Therapy];cytarabine/ae [Adverse Drug Reaction];doxorubicin/ae [Adverse Drug Reaction];etoposide/ae [Adverse Drug Reaction];fingolimod/ae [Adverse Drug Reaction];gemcitabine/ae [Adverse Drug Reaction];immunoglobulin/ae [Adverse Drug Reaction];immunoglobulin/iv [Intravenous Drug Administration];interferon/ae [Adverse Drug Reaction];manganese/to [Drug Toxicity];methotrexate/ae [Adverse Drug Reaction];rapamycin/ae [Adverse Drug Reaction];rituximab/ae [Adverse Drug Reaction];sorafenib/ae [Adverse Drug Reaction];sunitinib/ae [Adverse Drug Reaction];tacrolimus/ae [Adverse Drug Reaction];vincristine/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Tormoehlen, L. M.;Kumar, N.",2012,December,http://dx.doi.org/10.1212/CPJ.0b013e318278be1e,0,0,
1569,In vivo detection of copper ions by magnetic resonance imaging using a prion-based contrast agent,"Abnormal distributions of transition metals inside the body are potential diagnostic markers for several diseases, including Alzheimer's disease, Parkinson's disease, Wilson's disease, and cancer. In this article, we demonstrate that P57/Gd, a novel prion-based contrast agent, can selectively image tissues with excessive copper accumulation using magnetic resonance imaging (MRI). P57/Gd selectivity binds copper(II) over other physiologically relevant cations such as zinc, iron, manganese, and calcium. To simulate a metabolic copper disorder, we treated mice with an intraperitoneal injection of a CuSO<inf>4</inf> solution to induce a renal copper overload. The MRI signal intensities from the renal cortex and medulla of copper spiked animals that were administered P57/Gd were found to correlate with the ex vivo copper concentrations determined by inductively coupled plasma mass spectrometry. © Springer Science+Business Media, LLC 2012.",Angiogenesis;Copper;In vivo test;MRI (magnetic resonance imaging);Peptide;amino acid sequence;animal experiment;animal model;animal tissue;article;binding affinity;complex formation;controlled study;copper deficiency/dt [Drug Therapy];drug half life;kidney cortex;kidney medulla;male;mass spectrometry;metal binding;mouse;nonhuman;nuclear magnetic resonance imaging;peptide synthesis;protein binding;calcium;contrast medium/dv [Drug Development];contrast medium/iv [Intravenous Drug Administration];contrast medium/pk [Pharmacokinetics];copper sulfate/dt [Drug Therapy];copper sulfate/ip [Intraperitoneal Drug Administration];cyclin dependent kinase inhibitor 1C;gadolinium;gadoteric acid;iron;manganese;peptide P57 gadolinium/dv [Drug Development];peptide P57 gadolinium/iv [Intravenous Drug Administration];peptide P57 gadolinium/pk [Pharmacokinetics];prion protein;unclassified drug;zinc,"Makino, S.;Umemoto, T.;Yamada, H.;Yezdimer, E. M.;Tooyama, I.",2012,October,http://dx.doi.org/10.1007/s12010-012-9792-7,0,0,
1570,Therapeutic suggestions in occult chronic hypertransaminasemia,"Less than 25% of asymptomatic adults have elevated levels of transaminases on a first evaluation, one third of these patients have normal values on a retest. From those who have elevated ALT on retest, some prove to suffer from an acute liver disease (with normal ALT in less than 6 months), and the others represent the category of chronic (more than 6 months) elevation of transaminases. The etiology of chronic hypertransaminasemia can be elucidated in 90% of the cases, due to liver disease with occult/ atypical evolution, or extra-hepatic causes of chronic elevation of transaminases. The 10% left represent the category of unexplained (obscure cause) elevation of transaminases. The occult/atypical evolution liver diseases are represented by chronic viral hepatitis (HBV, HCV), alcohol consumption, non-alcoholic steatohepatitis (NASH), congestion liver, drugs and liver toxic substances, autoimmune hepatitis, Wilson's disease, a1 antitrypsin deficiency, parasitic diseases. The extra-hepatic causes that can determinate chronic elevations of transaminases are haemolysis, soft muscle diseases (polymyositis), occult celiac sprue, suprarenal insufficiency, thyroid pathology. There still remains 10% of the patients in witch the etiology can not be explained. Usually these patients are kept under surveillance, periodic reevaluation, and undergo a second liver biopsy; witch may reveal nonspecific lesions, NASH, chronic hepatitis, cirrhosis. There are cases in witch on the surveillance period it was observed a spontaneous normalization of transaminases. Chronic hypertransaminasemia is quite frequent, and has a high addressability to the physician from patients with this type of pathology, being for most of them a discovery by chance on a routine blood check. It is also important to have a clear diagnosis to start the specific treatment for those patients who can benefit out of it as soon as possible. © 2012.",Autoimmune hepatitis;Chronic hepatitis;Cirrhosis;Liver biopsy;nash;Wilson's disease;alcohol consumption;alpha 1 antitrypsin deficiency;aminotransferase blood level;article;blood analysis;celiac disease;chronic hypertransaminasemia/dt [Drug Therapy];chronic hypertransaminasemia/th [Therapy];disease surveillance;hemolysis/dt [Drug Therapy];hepatitis/si [Side Effect];hepatitis B;hepatitis C;human;hypertransaminasemia/dt [Drug Therapy];hypertransaminasemia/th [Therapy];kidney failure;liver congestion;liver toxicity;nonalcoholic fatty liver;nonhuman;parasitism;polymyositis/dt [Drug Therapy];thyroid disease;Wilson disease/dt [Drug Therapy];acetylsalicylic acid/ae [Adverse Drug Reaction];alanine aminotransferase/ec [Endogenous Compound];antiinflammatory agent/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];folic acid/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];isoniazid/ae [Adverse Drug Reaction];methyldopa/ae [Adverse Drug Reaction];oral contraceptive agent/ae [Adverse Drug Reaction];paracetamol/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];rifampicin/ae [Adverse Drug Reaction];ursodeoxycholic acid/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Adriana, N.;Cristina, O.;Olariu, M.;Olteanu, D.",2012,,,0,0,
1571,Progressive familial intrahepatic cholestasis type 3: Overlapping presentation with Wilson disease,,adolescent;alanine aminotransferase blood level;albumin blood level;alkaline phosphatase blood level;article;ascites;aspartate aminotransferase blood level;bilirubin blood level;case report;ceruloplasmin blood level;chelation therapy;child;clinical feature;drug withdrawal;familial disease/di [Diagnosis];familial disease/dt [Drug Therapy];female;gamma glutamyl transferase blood level;hepatosplenomegaly;histopathology;human;human tissue;intrahepatic cholestasis/di [Diagnosis];intrahepatic cholestasis/dt [Drug Therapy];liver biopsy;liver level;male;mutational analysis;preschool child;progressive familial intrahepatic cholestasis type 3/dt [Drug Therapy];progressive familial intrahepatic cholestasis type 3/di [Diagnosis];urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ABC transporter/ec [Endogenous Compound];abcb4 protein/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];trientine/dt [Drug Therapy];unclassified drug;ursodeoxycholic acid/dt [Drug Therapy],"Ramraj, R.;Finegold, M. J.;Karpen, S. J.",2012,July,http://dx.doi.org/10.1177/0009922812451076,0,0,
1572,Can mothers with wilson's disease give her breast milk to their infant?. [Japanese],"Background : Wilson's disease is a genetic disorder characterized by accumulation of copper in various tissues. In order to remove copper accumulated in the body, the patients are treated with administration of trientine, penicillamine or zinc. These treatments should be continued throughout their life. Recently, breastfeeding is recommended for babies in the world. When female patients with Wilson's disease have a baby, they want to breastfeed their infants even while continuing their treatment for Wilson's disease. However, no studies have been carried out on the safety of the breast milk feeding of the mother who is under treatment for Wilson's disease. This study deals with the safety of the breast milk feeding of mothers under treatment of Wilson's disease. Materials and Methods : Breast milks were obtained from 4, 4 and 2 patients with Wilson's disease who were under treatment with trientine, penicillamine and zinc, respectively. As control breast milk, Colostrums, transitional and mature milks were obtained from 16, 6 and 11 healthy mothers, respectively. The copper and zinc concentrations in the breast milk were analyzed by an atomic absorption spectrometry. At the same time, the distribution profiles of copper in the breast milk were also analyzed by HPLC-ICP-MS. Copper level bound with trientine or penicillamine in the patients was also analyzed by HPLC-ICP-MS. Results and Discussion : The copper and zinc concentrations were almost normal in the breast milk from mothers with Wilson's disease treated with the medicines described above. A slightly higher concentration of zinc and copper was detected in a few breast milks from the patients, but these levels were within those of infant formula. In HPLC-ICP-MS analysis of the breast milk from these mothers, the highest peak was detected in lactoalbumin-bound copper. No peak of trientine and penicillamine was detected in the milk. Conclusions : These results suggest that mothers with Wilson's disease can give her breast milks to their babies even when they are continuing the treatment for Wilson's disease.",Breast feeding;Copper;Wilson's disease;Zinc;article;artificial milk;atomic absorption spectrometry;atomic emission spectrometry;breast milk;clinical article;colostrum;controlled study;drug milk level;female;high performance liquid chromatography;human;infant;mother;risk assessment;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];lactalbumin;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Izumi, Y.",2012,January,,0,0,
1573,"Chelation: A fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications","This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications. © 2012 by the American Diabetes Association.",albuminuria;cardiovascular disease;chelation;chelation therapy;diabetes mellitus/dt [Drug Therapy];diabetes mellitus/et [Etiology];diabetic angiopathy;drug megadose;glucose metabolism;human;hyperglycemia/dt [Drug Therapy];insulin dependent diabetes mellitus;iron chelation;kidney disease/pc [Prevention];lipid peroxidation;non insulin dependent diabetes mellitus;nonhuman;priority journal;renal protection;review;streptozocin diabetes;Wilson disease;2 isopropylidenehydrazono 4 oxo 5 thiazolidinylacetanilide/an [Drug Analysis];2 isopropylidenehydrazono 4 oxo 5 thiazolidinylacetanilide/dt [Drug Therapy];advanced glycation end product;alagebrium/an [Drug Analysis];alagebrium/pd [Pharmacology];aldose reductase inhibitor/an [Drug Analysis];aldose reductase inhibitor/pd [Pharmacology];alt 462/an [Drug Analysis];alt 486/an [Drug Analysis];aminoguanidine/an [Drug Analysis];aminoguanidine/cm [Drug Comparison];aminoguanidine/dt [Drug Therapy];aminoguanidine/pk [Pharmacokinetics];aminoguanidine/pd [Pharmacology];angiotensin receptor antagonist/an [Drug Analysis];angiotensin receptor antagonist/pd [Pharmacology];ave 8048;benazepril/pd [Pharmacology];benfotiamine/an [Drug Analysis];benfotiamine/pd [Pharmacology];carnosine/an [Drug Analysis];cocarboxylase/an [Drug Analysis];dipeptidyl carboxypeptidase inhibitor/an [Drug Analysis];dipeptidyl carboxypeptidase inhibitor/pd [Pharmacology];hydralazine/cm [Drug Comparison];hydralazine/pd [Pharmacology];ilepatril/pd [Pharmacology];lr 9/an [Drug Analysis];norphenazone;nz 314;olmesartan/cm [Drug Comparison];olmesartan/pd [Pharmacology];penicillamine/dt [Drug Therapy];pyridoxamine/an [Drug Analysis];pyridoxamine/pd [Pharmacology];ramipril/cm [Drug Comparison];temocaprilat/pd [Pharmacology];tenilsetam/an [Drug Analysis];tenilsetam/dt [Drug Therapy];thiamine/pd [Pharmacology];thioctic acid/an [Drug Analysis];tm 2002/an [Drug Analysis];trc 4149/an [Drug Analysis];trc 4149/pd [Pharmacology];trc 4186/an [Drug Analysis];trc 4186/pd [Pharmacology];unclassified drug;unindexed drug;valsartan/pd [Pharmacology],"Nagai, R.;Murray, D. B.;Metz, T. O.;Baynes, J. W.",2012,March,http://dx.doi.org/10.2337/db11-1120,0,0,
1574,EASL Clinical Practice Guidelines: Wilson's disease (European association or the study of the liver,"This Clinical Practice Guideline (CPG) has been developed to assist physicians and other healthcare providers in the diagnosis and management of patients with Wilson's disease. The goal is to describe a number of generally accepted approaches for diagnosis, prevention, and treatment of Wilson's disease. Recommendations are based on a systematic literature review in the Medline (PubMed version), Embase (Dialog version), and the Cochrane Library databases using entries from 1966 to 2011. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system used in other EASL CPGs was used and set against the somewhat different grading system used in the AASLD guidelines (Table 1A and B). Unfortunately, there is not a single randomized controlled trial conducted in Wilson's disease which has an optimal design. Thus, it is impossible to assign a high or even a moderate quality of evidence to any of the questions dealt with in these guidelines. The evaluation is mostly based on large case series which have been reported within the last decades. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",abortion/si [Side Effect];acute liver failure/co [Complication];adjuvant therapy;ageusia/si [Side Effect];aminoaciduria;amylase blood level;anorexia;aplasia/si [Side Effect];article;ascites;ataxia;bioaccumulation;bleeding tendency;bone marrow depression/si [Side Effect];bone marrow toxicity/si [Side Effect];brain dysfunction/si [Side Effect];breast feeding;cardiomyopathy;central serous retinopathy/si [Side Effect];ceruloplasmin blood level;chelation therapy;cholestasis;chondrocalcinosis;chronic hepatitis;clinical trial (topic);Cochrane Library;computer assisted tomography;contraception;differential diagnosis;disease association;disease exacerbation/si [Side Effect];Doppler echography;drug dose reduction;drug withdrawal;elastosis/si [Side Effect];Embase;genetic screening;gigantism;Goodpasture syndrome/si [Side Effect];HELLP syndrome;hematuria/si [Side Effect];hemolysis;hemolytic anemia;hemosiderosis/si [Side Effect];hepatomegaly;histochemistry;human;hypercalciuria;immunoassay;immunoglobulin A deficiency/si [Side Effect];impulsiveness;infertility;jaundice;kidney calcification;lichen planus/si [Side Effect];literature;liver biopsy;liver cirrhosis;liver hemosiderosis/si [Side Effect];liver histology;liver necrosis;liver parenchyma;liver toxicity/si [Side Effect];liver transplantation;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];Medline;mental deterioration;mental disease;mutational analysis;myasthenia gravis/si [Side Effect];myopathy;nephrolithiasis;nephrotoxicity/si [Side Effect];neurologic disease;neuroradiology;neutropenia/si [Side Effect];nonalcoholic fatty liver;nuclear magnetic resonance imaging;osteoarthritis;pancreatitis;Parkinson disease;personality disorder;polymyositis/si [Side Effect];portal hypertension;postoperative complication/co [Complication];practice guideline;pregnancy;priority journal;prognosis;proteinuria/si [Side Effect];rash/si [Side Effect];side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];siderosis/si [Side Effect];single photon emission computer tomography;slit lamp;splenomegaly;spontaneous abortion;steatosis;stomach irritation/si [Side Effect];systematic review;teratogenicity/si [Side Effect];thrombocytopenia/si [Side Effect];tremor;triacylglycerol lipase blood level;urinalysis;urine volume;virus hepatitis;vomiting;Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];Wilson disease/su [Surgery];4 phenylbutyric acid/dt [Drug Therapy];4 phenylbutyric acid/pd [Pharmacology];alpha tocopherol/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;curcumin/dt [Drug Therapy];curcumin/pd [Pharmacology];dimercaprol/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];pyridoxine;tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics];Wilson disease protein/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/pd [Pharmacology];zinc sulfate/dt [Drug Therapy],Anonymous,2012,March,http://dx.doi.org/10.1016/j.jhep.2011.11.007,0,0,
1575,Editor's note,,alcohol liver disease;anemia/dt [Drug Therapy];critical illness;drug absorption;editorial;education program;enteritis;feeding disorder;health program;hepatic encephalopathy;human;hypophosphatemia/co [Complication];liver cell carcinoma;macronutrient;medical literature;monotherapy;parenteral nutrition;refeeding syndrome;thiamine deficiency/dt [Drug Therapy];virus hepatitis;Wilson disease;zinc deficiency/dt [Drug Therapy];zinc metabolism;ascorbic acid;cyanocobalamin/dt [Drug Therapy];essential amino acid;fish oil;folic acid/dt [Drug Therapy];iron/dt [Drug Therapy];selenium;thiamine/dt [Drug Therapy];thiamine/pk [Pharmacokinetics];trace element;vitamin D;zinc/dt [Drug Therapy],"Hasse, J. M.",2012,February,http://dx.doi.org/10.1177/0884533612436468,0,0,
1576,Zinc and liver disease,"Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease (ALD) and viral liver disease. Some of the mechanisms for zinc deficiency/altered metabolism include decreased dietary intake, increased urinary excretion, activation of certain zinc transporters, and induction of hepatic metallothionein. Zinc deficiency may manifest itself in many ways in liver disease, including skin lesions, poor wound healing/liver regeneration, altered mental status, or altered immune function. Zinc supplementation has been documented to block/attenuate experimental ALD through multiple processes, including stabilization of gut-barrier function, decreasing endotoxemia, decreasing proinflammatory cytokine production, decreasing oxidative stress, and attenuating apoptotic hepatocyte death. Clinical trials in human liver disease are limited in size and quality, but it is clear that zinc supplementation reverses clinical signs of zinc deficiency in patients with liver disease. Some studies suggest improvement in liver function in both ALD and hepatitis C following zinc supplementation, and 1 study suggested improved fibrosis markers in hepatitis C patients. The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea. © 2012 The American Society for Parenteral and Enteral Nutrition.",alcoholic;hepatitis;liver cirrhosis;liver diseases;zinc;acne/dt [Drug Therapy];acrodermatitis;acrodermatitis enteropathica;alcohol liver disease;alopecia;anorexia;apoptosis;brain disease;cell death;cell growth;cellular immunity;clinical trial (topic);cytokine production;dandruff/dt [Drug Therapy];diaper dermatitis/dt [Drug Therapy];diarrhea;dietary intake;endotoxemia;eye disease;failure to thrive;fibrosis;gene expression;gene mutation;hepatic encephalopathy;Hepatitis B virus;hepatitis C;Hepatitis C virus;human;hyperammonemia;hypogonadism;infection;libido disorder;liver cell carcinoma;liver disease;liver function;liver regeneration;meal;mental function;mental health;nausea/dt [Drug Therapy];night vision;oxidative stress;parenteral nutrition;review;sepsis;skin defect;smelling disorder;spermatogenesis;spermatozoon count;spermatozoon motility;T lymphocyte;taste disorder;thymus atrophy;urinary excretion;virus hepatitis;weight reduction;Wilson disease;wound healing impairment;zinc deficiency;zinc metabolism;copper;cytokine/ec [Endogenous Compound];glutamate ammonia ligase/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];horseradish peroxidase/ec [Endogenous Compound];I kappa B kinase beta/ec [Endogenous Compound];lactulose/ec [Endogenous Compound];macrogol/ec [Endogenous Compound];mannitol/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];prealbumin/ec [Endogenous Compound];retinol/ec [Endogenous Compound];retinol binding protein/ec [Endogenous Compound];retinol dehydrogenase/ec [Endogenous Compound];somatomedin C/ec [Endogenous Compound];thymus hormone/ec [Endogenous Compound];tumor necrosis factor alpha/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc/pk [Pharmacokinetics];zinc transporter/ec [Endogenous Compound],"Mohommad, M. K.;Zhou, Z.;Cave, M.;Barve, A.;McClain, C. J.",2012,February,http://dx.doi.org/10.1177/0884533611433534,0,0,
1577,Are irreversible morpholocical signs of portal hypertension in neurological form of Wilson's disease associated with treatment delay? A pilot study,"Aim of this study was to evaluate the rate of morphological liver and spleen abnormalities in patients with neurological clinical presentation of Wilson's disease (WD). Fourteen patients with neurological presentation of WD divided into group A (5 patients who initiated chelating therapy <24 months from the first symptoms) and group B (9 patients whose therapy started >=24 months after the initial symptoms) underwent abdominal MRI examination. Abnormal findings on abdominal MRI were present in 28% of patients with neurological form of WD. Significant hepatosplenomegaly was present in none of the patients from group A and in 4 (44%) patients from group B. In addition, macronodular liver cirrhosis and peritoneal effusion were evident in two and one patient from group B, respectively, and in none of the patients from group A. Our results suggest that severe portal hypertension and liver damage in patients with neurological presentation of WD might be reversible or do not even develop if chelating treatment is initiated <2 years after the onset of symptoms. © 2012 Belgian Neurological Society.",Delayed diagnosis;Liver dysfunction;Wilson's disease;abdominal disease;abdominal radiography;adult;article;cerebellum disease;clinical article;clinical examination;clinical feature;controlled study;disease duration;dystonia;female;hepatosplenomegaly;human;liver cirrhosis;male;neurologic disease;nuclear magnetic resonance imaging;onset age;peritoneal effusion;pilot study;portal hypertension;pseudoparkinsonian;therapy delay;treatment duration;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];chelating agent;penicillamine/dt [Drug Therapy],"Kozic, D. B.;Semnic, R.;Petrovic, I.;Svetel, M.;Ostojic, J.;Kostic, V. S.",2012,September,http://dx.doi.org/10.1007/s13760-012-0025-1,0,0,
1578,Selective divalent copper chelation for the treatment of diabetes mellitus,"Oxidative stress and mitochondrial dysfunction have been identified by many workers as key pathogenic mechanisms in ageing-related metabolic, cardiovascular and neurodegenerative diseases (for example diabetes mellitus, heart failure and Alzheimer's disease). However, although numerous molecular mechanisms have been advanced to account for these processes, their precise nature remains obscure. This author has previously suggested that, in such diseases, these two mechanisms are likely to occur as manifestations of a single underlying disturbance of copper regulation. Copper is an essential but highly-toxic trace metal that is closely regulated in biological systems. Several rare genetic disorders of copper homeostasis are known in humans: these primarily affect various proteins that mediate intracellular copper transport processes, and can lead either to tissue copper deficiency or overload states. These examples illustrate how impaired regulation of copper transport pathways can cause organ damage and provide important insights into the impact of defects in specific molecular processes, including those catalyzed by the copper-transporting ATPases, ATP7A (mutated in Menkes disease), ATP7B (Wilson's disease), and the copper chaperones such as those for cytochrome c oxidase, SCO1 and SCO<inf>2</inf>. In diabetes, impaired copper regulation manifests as elevations in urinary Cu<sup>II</sup> excretion, systemic chelatable-Cu <sup>II</sup> and full copper balance, in increased pro-oxidant stress and defective antioxidant defenses, and in progressive damage to the blood vessels, heart, kidneys, retina and nerves. Linkages between dysregulated copper and organ damage can be demonstrated by Cu<sup>II</sup>-selective chelation, which simultaneously prevents/reverses both copper dysregulation and organ damage. Pathogenic structures in blood vessels that contribute to binding and localization of catalytically-active Cu<sup>II</sup> probably include advanced glycation endproducts (AGEs), as well as atherosclerotic plaque: the latter probably undergoes AGE-modification itself. Defective copper regulation mediates organ damage through two general processes that occur simultaneously in the same individual: elevation of Cu<sup>II</sup>-mediated pro-oxidant stress and impairment of copper-catalyzed antioxidant defence mechanisms. This author has proposed that diabetes-evoked copper dysregulation is an important new target for therapeutic intervention to prevent/reverse organ damage in diabetes, heart failure, and neurodegenerative diseases, and that triethylenetetramine (TETA) is the first in a new class of anti-diabetic molecules, which function by targetting these copper-mediated pathogenic mechanisms. TETA prevents tissue damage and causes organ regeneration by acting as a highly-selective Cu <sup>II</sup> chelator which suppresses copper-mediated oxidative stress and restores anti-oxidant defenses. My group has employed TETA in a comprehensive programme of nonclinical studies and proof-of-principle clinical trials, thereby characterizing copper dysregulation in diabetes and identifying numerous linked cellular and molecular mechanisms though which TETA exerts its therapeutic actions. Many of the results obtained in nonclinical models with respect to the molecular mechanisms of diabetic organ damage have not yet been replicated in patients' tissues so their applicability to the human disease must be considered as inferential until the results of informative clinical studies become available. Based on evidence from the studies reviewed herein, trientine is now proceeding into the later stages of pharmaceutical development for the treatment of heart failure and other diabetic complications. © 2012 Bentham Science Publishers.","Atherosclerosis;Copper deficiency;Copper overload;Copper-selective chelation;Diabetes mellitus;Diabetic arteriopathy;Diabetic cardiomyopathy;Diabetic nephropathy;Diabetic neuropathy;Diabetic retinopathy;Divalent copper;Experimental pharmacology;Experimental therapeutics;Heart failure;Hydroxyl radical;Iron regulation;Mitochondrial dysfunction;Organ regeneration;Oxidative stress;Randomized clinical trials;Superoxide anion;Superoxide dismutase;Triethylenetetramine (TETA);Zinc regulation;acetylation;article;atherosclerotic plaque;biliary excretion;binding site;bioavailability;cardiovascular disease;catalysis;cell death;central nervous system;ceruloplasmin blood level;cesarean section;chelation therapy;child development;chronic copper toxicity;computer assisted emission tomography;copper metabolism;corpus cavernosum;degenerative disease;diabetes mellitus/dt [Drug Therapy];diabetic angiopathy;diabetic patient;diet supplementation;disease severity;down regulation;drug dose escalation;drug effect;drug efficacy;drug excretion;drug safety;drug tolerability;enzyme activity;enzyme induction;excitotoxicity;extracellular matrix;genetic disorder;gestational age;glucose blood level;heart function;heart left ventricle mass;high risk patient;hippocampus;human;hyperglycemia;in vitro study;in vivo study;insulin dependent diabetes mellitus;kidney function;metabolic disorder;morbidity;mortality;non insulin dependent diabetes mellitus;nonhuman;nuclear magnetic resonance imaging;patient monitoring;pharmacodynamics;pharmacokinetics;pharmacology;phase 1 clinical trial (topic);phase 2 clinical trial (topic);physical chemistry;pregnancy;prematurity;proteinuria;proteomics;retina blood vessel;risk factor;side effect/si [Side Effect];tissue injury;toxicity;treatment duration;treatment response;urinary excretion;Wilson disease;advanced glycation end product/ec [Endogenous Compound];amine oxidase (flavin containing);arylamine acetyltransferase/ec [Endogenous Compound];catalase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;copper exporting adenosine triphosphatase/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];cytochrome c oxidase/ec [Endogenous Compound];glucose;metallothionein/ec [Endogenous Compound];n,n' bis(2 aminoethyl) 1,3 propanediamine/cm [Drug Comparison];penicillamine;placebo;reactive oxygen metabolite/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];transforming growth factor beta/ec [Endogenous Compound];transforming growth factor beta1/ec [Endogenous Compound];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cm [Drug Comparison];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];Wilson disease protein/ec [Endogenous Compound];zinc","Cooper, G. J. S.",2012,June,,0,0,
1579,Chelating agents for neurodegenerative diseases,"It has become apparent in the last years that metal ion homeostasis and its dysfunction which results in increased accumulation in brain, notably of copper, iron and zinc, may be associated with a number of neurodegenerative diseases, such that chelation therapy may be one therapeutic option. We briefly outline chelators currently available together with strategies to develop new chelators capable of crossing the blood-brain-barrier. The homeostasis of iron in brain together with changes in brain iron with ageing are reviewed as well as the role of iron in Parkinson's disease, and the potential of chelation therapy in PD. Copper and zinc homeostasis in brain and ageassociated changes are then outlined, along with a discussion of the possible involvement of Zn, Cu and Fe in Alzheimer's disease. We conclude with a brief summary of chelation therapy in AD. © 2012 Bentham Science Publishers.","Chelation;Copper;Iron;Neurodegeneration;Zinc;aging;Alzheimer disease/dt [Drug Therapy];article;blood brain barrier;chelation therapy;copper deficiency;degenerative disease/dt [Drug Therapy];drug structure;human;iron blood level;neuropil;neuroprotection;nonhuman;Parkinson disease/dt [Drug Therapy];senile plaque;Wilson disease/dt [Drug Therapy];8 quinolinol/pd [Pharmacology];chelating agent/dt [Drug Therapy];clioquinol/dt [Drug Therapy];clioquinol/pd [Pharmacology];copper/ec [Endogenous Compound];deferasirox/dt [Drug Therapy];deferiprone/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];deferoxamine/im [Intramuscular Drug Administration];dp 109/dt [Drug Therapy];ethylene glycol 1,2 bis(2 aminophenyl) ether n,n,n',n' tetraacetic acid;ferritin/ec [Endogenous Compound];hla 20;iron/ec [Endogenous Compound];nanoparticle;oxidopamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];polyphenol/pd [Pharmacology];unclassified drug;zinc/ec [Endogenous Compound]","Ward, R. J.;Dexter, D. T.;Crichton, R. R.",2012,June,,0,0,
1580,Penicillamine increases free copper and enhances oxidative stress in the brain of toxic milk mice,"Wilson disease (WD) is characterized by the accumulation of copper arising from a mutation in the ATP7B gene. Penicillamine (PA) makes 10-50% of the patients with neurologic symptoms neurologically worse at the early stage of administration. The aim of this study was to determine how the copper metabolism changes and whether the change impairs the brain of toxic milk (tx) mice, an animal model of WD, during the PA administration. The free copper and protein-bound copper concentrations in the serum, cortex and basal ganglia of tx mice with PA administration for 3 days, 10 days and 14 days, respectively, were investigated. The expression of copper transporters, ATP7A and CTR1,was analyzed by real-time quantitative PCR, immunofluorescence and Western blot. Then SOD, MDA and GSH/GSSG were detected to determine whether the oxidative stress changed correspondingly. The results revealed the elevated free copper concentrations in the serum and brain, and declined protein-bound copper concentrations in the brain of tx mice during PA administration. Meanwhile, transiently increased expression of ATP7A and CTR1 was observed generally in the brain parenchyma by immunofluorescence, real-time quantitative PCR and Western blot. Additionally, ATP7A and CTR1 were observed to locate mainly at Golgi apparatus and cellular membrane respectively. Intense staining of ATP7A in the choroid plexus was found in tx mice on the 3rd and 10th day of PA treatment, but rare staining of ATP7A and CTR1 in the blood-brain barrier (BBB). Decreased GSH/GSSG and increased MDA concentrations were also viewed in the cortex and basal ganglia. Our results suggested the elevated free copper concentrations in the brain might lead to the enhanced oxidative stress during PA administration. The increased free copper in the brain might come from the copper mobilized from brain parenchyma cells but not from the serum according to the ATP7A and CTR1 expression analysis. © 2012 Chen et al.",animal experiment;animal model;animal tissue;article;basal ganglion;blood brain barrier;brain cortex;brain level;cell membrane;cellular distribution;choroid plexus;controlled study;copper blood level;copper metabolism;Golgi complex;immunofluorescence;mouse;nonhuman;oxidative stress;protein expression;protein localization;real time polymerase chain reaction;Western blotting;Wilson disease/dt [Drug Therapy];carrier protein/ec [Endogenous Compound];copper/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];glutathione disulfide/ec [Endogenous Compound];malonaldehyde/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];messenger RNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/ig [Intragastric Drug Administration];protein CTR1/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];unclassified drug,"Chen, D. B.;Feng, L.;Lin, X. P.;Zhang, W.;Li, F. R.;Liang, X. L.;Li, X. H.",2012,21 May,http://dx.doi.org/10.1371/journal.pone.0037709,0,0,
1581,Current and future techniques in the evaluation of dysphagia,"Dysphagia is common in the general population, and is generally due to either mechanical obstruction or dysmotility. Patient demographics and symptom evaluation are often useful in determining the likely cause, and guide subsequent investigation and management. Oropharyngeal dysphagia is usually caused by neurological conditions where treatment options are limited. Conversely, many of the esophageal causes of dysphagia are amenable to therapy. Gastroscopy is often the first test of choice, given its diagnostic and therapeutic potential, especially when mechanical causes are concerned. Esophageal motor function can be assessed by a variety of techniques, ranging from radiology such as barium swallow, to dedicated motility tests such as manometry and impedance monitoring. The choice of test relies on the clinical indication and the results should be interpreted in conjunction with the patients' symptoms. High-resolution manometry with topography is now the new benchmark for motility studies. Several new techniques for motility testing have also become available, such as esophageal ultrasound and functional lumen imaging probe, but are currently limited to the research setting. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.",Dysphagia technique;Endoscopy: upper gastrointestinal;Esophageal motility;Esophagus;Alzheimer disease;article;clinical assessment;clinical feature;dysphagia/co [Complication];dysphagia/di [Diagnosis];dysphagia/dt [Drug Therapy];dysphagia/si [Side Effect];esophagus dysphagia/co [Complication];esophagus dysphagia/di [Diagnosis];esophagus dysphagia/dt [Drug Therapy];esophagus function;esophagus motility;gastroscopy;Guillain Barre syndrome;head and neck surgery;human;Huntington chorea;manometry;motor neuron disease;motor performance;myasthenia gravis;oropharynx dysphagia/co [Complication];oropharynx dysphagia/di [Diagnosis];oropharynx dysphagia/si [Side Effect];oropharynx tumor;paraneoplastic syndrome;Parkinson disease;patient assessment;polymyositis;priority journal;radiotherapy;scintigraphy;spinal muscular atrophy;stroke;symptom;thyrotoxicosis;topography;ultrasound;Wilson disease;xerostomia/dt [Drug Therapy];Zenker diverticulum;aminoglycoside/ae [Adverse Drug Reaction];amiodarone/ae [Adverse Drug Reaction];antidepressant agent/ae [Adverse Drug Reaction];antihistaminic agent/ae [Adverse Drug Reaction];antihypertensive agent/ae [Adverse Drug Reaction];antiparkinson agent/ae [Adverse Drug Reaction];atypical antipsychotic agent/ae [Adverse Drug Reaction];barium;benzodiazepine derivative/ae [Adverse Drug Reaction];botulinum toxin/ae [Adverse Drug Reaction];cholinergic receptor blocking agent/dt [Drug Therapy];cyclosporin/ae [Adverse Drug Reaction];digoxin/ae [Adverse Drug Reaction];diuretic agent/ae [Adverse Drug Reaction];dopamine receptor blocking agent/dt [Drug Therapy];erythromycin/ae [Adverse Drug Reaction];hydroxymethylglutaryl coenzyme A reductase inhibitor/ae [Adverse Drug Reaction];metoclopramide/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];phenothiazine derivative/ae [Adverse Drug Reaction];procainamide/ae [Adverse Drug Reaction];trichloroethylene/ae [Adverse Drug Reaction];vincristine/ae [Adverse Drug Reaction],"Kuo, P.;Holloway, R. H.;Nguyen, N. Q.",2012,May,http://dx.doi.org/10.1111/j.1440-1746.2012.07097.x,0,0,
1582,Further rare and unusual dementias,"In the second of two articles on rare causes of dementia, the authors describe toxic, iatrogenic, nutritional, traumatic, metabolic, neoplastic and autoimmune causes of dementia. Disorders are graded according to their prevalence, to give an idea of the likelihood of their presentation. Guidance is given on the investigation of uncommon cognitive impairment and dementia, especially in early-onset illness.","adrenoleukodystrophy/et [Etiology];agitation;alcohol consumption;amnesia;amyotrophic lateral sclerosis;anterograde amnesia/co [Complication];arsenic poisoning/dt [Drug Therapy];Behcet disease;bleeding;brain disease/co [Complication];brain dysfunction/si [Side Effect];brain hypoxia/et [Etiology];brain ventricle peritoneum shunt;cadasil;carcinoid syndrome;cardiomegaly;celiac disease;cerebellar ataxia/co [Complication];cerebral sinus thrombosis/co [Complication];chelation therapy;chorea/co [Complication];choreoathetosis;cognitive defect/co [Complication];cognitive defect/dt [Drug Therapy];cognitive defect/si [Side Effect];cognitive therapy;computer assisted tomography;confusion;cyanocobalamin deficiency/dt [Drug Therapy];cyanocobalamin deficiency/et [Etiology];dementia/si [Side Effect];dementia/co [Complication];dementia/et [Etiology];dementia pugilistica/et [Etiology];depression/co [Complication];dermatitis;diabetes mellitus;dialysis;dialysis encephalopathy;diarrhea;diffusion weighted imaging;DiGeorge syndrome;disease association;electroencephalography;electromyography;endocarditis/co [Complication];environmental exposure;enzyme replacement;erythrocyte sedimentation rate;fatigue;flapping tremor;folic acid deficiency/et [Etiology];glioma/et [Etiology];glomerulonephritis/co [Complication];Hartnup disease/cn [Congenital Disorder];Hashimoto disease;head injury;hematopoietic stem cell transplantation;hepatic encephalopathy/dt [Drug Therapy];hormone substitution;human;hyperparathyroidism/et [Etiology];hypocalcemia/dt [Drug Therapy];hypocalcemia/et [Etiology];hypoparathyroidism;hypothyroidism/dt [Drug Therapy];kidney graft;lead poisoning/dt [Drug Therapy];lethargy;lipidosis/et [Etiology];lithium blood level;liver biopsy;liver graft;lumbar puncture;meningioma;meningoencephalitis/co [Complication];mercurialism/dt [Drug Therapy];metachromatic leukodystrophy/et [Etiology];migraine/co [Complication];multiple sclerosis;myoclonus;neoplasm/dt [Drug Therapy];neuroacanthocytosis/et [Etiology];neurodegeneration with brain iron accumulation/di [Diagnosis];neurodegeneration with brain iron accumulation/dt [Drug Therapy];neuroimaging;neuromuscular junction disorder;neurotoxicity/si [Side Effect];nicotinic acid deficiency/dt [Drug Therapy];nicotinic acid deficiency/et [Etiology];Niemann Pick disease/et [Etiology];normotensive hydrocephalus;paraneoplastic neuropathy;paraneoplastic syndrome;parathyroidectomy;Parkinson disease;pellagra/dt [Drug Therapy];pellagra/et [Etiology];pericarditis/co [Complication];peripheral neuropathy/co [Complication];pleurisy/co [Complication];pneumonia/co [Complication];positron emission tomography;protein restriction;psychosis/co [Complication];rare disease/et [Etiology];retrograde amnesia/co [Complication];review;rheumatoid arthritis;Sandhoff disease/et [Etiology];sarcoidosis;scleroderma;seizure/co [Complication];sensory neuropathy/co [Complication];Sjoegren syndrome;spinal cord disease/co [Complication];stroke/co [Complication];stupor;subdural hematoma/et [Etiology];systemic lupus erythematosus;systemic vasculitis;Tay Sachs disease/et [Etiology];tremor;urine incontinence;vasculitis;virus infection/dt [Drug Therapy];Wernicke Korsakoff syndrome/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];3,4 methylenedioxymethamphetamine/ae [Adverse Drug Reaction];alcohol/ae [Adverse Drug Reaction];alpha interferon/ae [Adverse Drug Reaction];aluminum/to [Drug Toxicity];arsenic/to [Drug Toxicity];calcium/dt [Drug Therapy];calcium/po [Oral Drug Administration];cannabis/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];cocaine/ae [Adverse Drug Reaction];cyanocobalamin/dt [Drug Therapy];cyanocobalamin/pa [Parenteral Drug Administration];dimercaprol/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];edetate calcium disodium/dt [Drug Therapy];flumazenil/dt [Drug Therapy];glucocorticoid/ae [Adverse Drug Reaction];interferon/dt [Drug Therapy];lactulose/dt [Drug Therapy];lead/to [Drug Toxicity];levodopa/dt [Drug Therapy];levothyroxine/dt [Drug Therapy];lithium;manganese/to [Drug Toxicity];mercury/to [Drug Toxicity];nicotinic acid/dt [Drug Therapy];nicotinic acid/po [Oral Drug Administration];opiate antagonist/dt [Drug Therapy];organophosphate/to [Drug Toxicity];organophosphate pesticide/to [Drug Toxicity];penicillamine/dt [Drug Therapy];succimer/dt [Drug Therapy];unindexed drug","Gupta, S.;Fiertag, O.;Thanulingam, T.;Ros, E.;Strange, B.;Warner, J.",2012,January,http://dx.doi.org/10.1192/apt.bp.107.004804,0,0,
1583,Other genetic liver diseases in children,"Wilson disease is rare but proteiform, and should be suspected in any child with liver disease and older than 3 years of age. The treatment is very efficient, and must be taken life-long. Fifteen percent of patients with alpha-1-antitrypsin deficiency develop a neonatal jaundice, and 3% a cirrhosis in childhood. There is no specific treatment except liver transplantation. Five percent of cystic fibrosis patients develop a cirrhosis, with a very slow progression. Milder abnormalities are frequent, as well as biliary stones. Liver disease in ciliopathies may be a congenital hepatic fibrosis, with risks of portal hypertension and cholangitis, or a more variable biliary disease. Gilbert disease is frequent and benign. Crigler-Najjar syndrome is rare, severe, and may be an indication for liver or liver-cell transplantation. © 2012 Elsevier Masson SAS.",alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/ep [Epidemiology];alpha 1 antitrypsin deficiency/et [Etiology];alpha 1 antitrypsin deficiency/su [Surgery];article;biliary tract disease;ceruloplasmin blood level;child;childhood disease/di [Diagnosis];childhood disease/ep [Epidemiology];childhood disease/et [Etiology];childhood disease/su [Surgery];cholangitis;congenital liver fibrosis/cn [Congenital Disorder];congenital liver fibrosis/di [Diagnosis];congenital liver fibrosis/ep [Epidemiology];Crigler Najjar syndrome/cn [Congenital Disorder];Crigler Najjar syndrome/su [Surgery];Crigler Najjar syndrome/th [Therapy];cystic fibrosis/di [Diagnosis];cystic fibrosis/dt [Drug Therapy];cystic fibrosis/ep [Epidemiology];disease association;disease severity;drug efficacy;drug safety;drug tolerability;fulminant hepatic failure/su [Surgery];gene therapy;genetic disorder/di [Diagnosis];genetic disorder/ep [Epidemiology];genetic disorder/et [Etiology];genetic disorder/su [Surgery];Gilbert disease;hepatocyte transplantation;heterozygote;homozygote;human;incidence;jaundice;liver biopsy;liver cirrhosis/su [Surgery];liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/ep [Epidemiology];liver disease/et [Etiology];liver disease/su [Surgery];liver fibrosis/cn [Congenital Disorder];liver fibrosis/di [Diagnosis];liver fibrosis/ep [Epidemiology];liver function test;liver polycystic disease/di [Diagnosis];liver polycystic disease/ep [Epidemiology];liver transplantation;nuclear magnetic resonance imaging;pathophysiology;portal hypertension;risk factor;unspecified side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];alpha 1 antitrypsin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];transmembrane conductance regulator/ec [Endogenous Compound];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Lacaille, F.",2012,June,http://dx.doi.org/10.1016/j.clinre.2012.03.027,0,0,
1584,New novel mutation of the ATP7B gene in a family with Wilson disease,"Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The WD gene codes for a copper transporting P-type ATPase (ATP7B) are located on chromosome 13q14.3. Mutation of this gene disrupts copper homeostasis, resulting in the accumulation of copper in the liver, brain, kidneys and corneas and copper toxication at these sites. Since the detection of the WD gene in 1993, approximately 300 disease-specific muations have been identified. We recently evaluated a Korean family with WD. The proband, a 17-year-old boy, visited our hospital due to abnormal behaviors including generalized slow movement, dysphagia, drooling and ataxia. Laboratory results revealed decreases in serum copper and ceruloplasmin and an increase in urinary excretion of copper. He had liver cirrhosis, brain lesions and Kayser-Fleischer corenal rings. Molecular genetic analysis of the ATP7B gene demonstrated that he was heterozygous for deletion mutation c.2697-2723del27 in exon 11. Further study of family members revealed that his father and younger brother had the same mutation. The c.2697-2723del27 deletion mutation in exon 11 has not yet been reported as a causative muation of WD and is an in-frame deletion not expected to lead to a frame shift. Therefore, we report a novel mutation of the ATP7B gene in a family with WD. © 2011 Elsevier B.V. All rights reserved.",13q14.3;atp7b;Hepatolenticular degeneration;Wilson disease;adolescent;article;case report;clinical feature;disease course;gene mutation;gene sequence;genetic analysis;human;laboratory test;male;nuclear magnetic resonance imaging;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Lee, J. Y.;Kim, Y. H.;Kim, T. W.;Oh, S. Y.;Kim, D. S.;Shin, B. S.",2012,15 Feb,http://dx.doi.org/10.1016/j.jns.2011.09.007,0,0,
1585,"Elevated liver enzymes, anaemia and osteopaenia in a young woman","A 23-year-old woman presented with elevated liver enzymes, anaemia and lower limb oedema. Iron-deficiency anaemia due to gynaecological problems was suspected. The patient was treated with iron supplements normalising the blood haemoglobin. Alcohol binge drinking was suspected to be the cause of elevated liver enzymes. After 7 years, the patient presented to our outpatient clinic with nonspecific gastrointestinal symptoms. Blood tests revealed low levels of serum s-iron and elevated liver function tests. Abdominal ultrasound was normal. No signs of viral hepatitis or hereditary liver disease were detected. There was a marked elevation of tissue transglutaminase antibodies. A small intestine biopsy confirmed the diagnosis of coeliac disease. A bone density scan showed osteopaenia. Following a gluten-free, lactose-reduced diet, the gastrointestinal symptoms disappeared and s-transaminase activity and s-iron levels normalised. Copyright 2012 BMJ Publishing Group. All rights reserved.",adult;alanine aminotransferase blood level;antibody detection;article;aspartate aminotransferase blood level;bone density;case report;celiac disease/di [Diagnosis];celiac disease/th [Therapy];clinical feature;differential diagnosis;duodenum biopsy;echocardiography;endoscopic retrograde cholangiopancreatography;fatigue;female;ferritin blood level;follow up;gastroscopy;gluten free diet;hemochromatosis/di [Diagnosis];human;human tissue;hypertransaminasemia/di [Diagnosis];iron deficiency anemia/co [Complication];iron deficiency anemia/di [Diagnosis];iron deficiency anemia/th [Therapy];iron therapy;osteopenia/di [Diagnosis];peripheral edema;postpartum hemorrhage;priority journal;quality of life;scoring system;systolic heart murmur/di [Diagnosis];transferrin blood level;treatment outcome;virus hepatitis/di [Diagnosis];vitamin blood level;vitamin supplementation;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];calcium;ferritin/ec [Endogenous Compound];folic acid;immunoglobulin G antibody/ec [Endogenous Compound];immunoglobulin M antibody/ec [Endogenous Compound];iron;mitochondrion antibody/ec [Endogenous Compound];multivitamin;neutrophil cytoplasmic antibody/ec [Endogenous Compound];smooth muscle antibody/ec [Endogenous Compound];transferrin/ec [Endogenous Compound];vitamin D;zinc,"Nielsen, B. R.;Schwarz, P.;Friis, S.;Gluud, L. L.",2012,,http://dx.doi.org/10.1136/bcr-03-2012-6112,0,0,
1586,Successful liver transplantation following veno-arterial extracorporeal membrane oxygenation in a child with fulminant Wilson disease and severe pulmonary hemorrhage: A case report,"Massive pulmonary hemorrhage and other serious cardiopulmonary diseases in patients with fulminant hepatitis result not only in graft failure but also mortality after LT. ECMO is used to treat children with cardiorespiratory failure refractory to conventional intensive care. We describe a five-yr-old girl with genetically confirmed fulminant Wilson disease and severe pulmonary hemorrhage who underwent successful primary LT following veno-arterial ECMO. To our knowledge, this is the first report of successful primary LT in a patient using veno-arterial ECMO. The present case demonstrates that ECMO, as a bridging modality to LT, may be necessary to manage both massive pulmonary hemorrhage and possible graft loss because of hypoxemia. © 2011 John Wiley & Sons A/S.",acute liver failure;fulminant hepatic failure;pediatric liver transplantation;respiratory insufficiency;Wilson's disease;arterial oxygen saturation;arterial oxygen tension;article;ascites;breathing rate;case report;child;disease course;endotracheal tube;epistaxis;extracorporeal oxygenation;female;follow up;heart rate;human;international normalized ratio;jaundice;leukocyte count;liver transplantation;lung hemorrhage/di [Diagnosis];partial thromboplastin time;preschool child;prothrombin time;reticulocyte;thrombocyte count;treatment outcome;urea nitrogen blood level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Son, S. K.;Oh, S. H.;Kim, K. M.;Lee, Y. J.;Jhang, W. K.;Park, S. J.;Shin, H. J.;Park, J. J.;Kim, T. H.;Kim, D. Y.;Hwang, S.;Park, K. M.;Lee, Y. J.;Lee, S. G.",2012,November,http://dx.doi.org/10.1111/j.1399-3046.2011.01604.x,0,0,
1587,Wilson disease in 71 patients followed for over two decades in a tertiary center in Saudi Arabia: A retrospective review,"Background and objectives: Wilson disease (WD) is a rare autosomal recessive disease. Our objective was to describe the diverse patterns, therapies, and outcomes of this disease. DESIGN AND SETTING: A retrospective study over two decades on WD patients in a tertiary care center in Saudi Arabia. Patients and Methods: Clinical and laboratory findings of 71 patients with WD were retrieved from their charts, referral notes and our hospital electronic records and were analyzed. Results: The mean age and standard deviation was 16.8 (10.7) years and 56.5% were males. The main manifestations of WD were hepatic, neurological, and mixed in 39 (54.9%), 12 (16.9%), and 20 (28.2%) patients, respectively, and 11 (15.5%) were asymptomatic cases detected by family screening. A family history of WD was positive in 41 (57.7%) patients, and consanguinity of parents was found in 26 (36.6%) patients. The mean (SD) follow-up period was 92.2 (72.9) (range, 1-320) months. Ten (14.1%) patients died during follow up, while 45 (63.4%) and 16 (22.5%) were still on or lost from follow-up, respectively. The mean (SD) age at the end of follow- up was 25.3 (12) (range, 4-62) years. Hepatoma was discovered in 5 (7.0%) patients. Penicillamine therapy was used by 58 (81.7%) patients, while zinc and trientine were given to 32 (45.1%) and 11 (15.5%) patients, respectively. Sixteen (22.5%) patients underwent liver transplantation and one died (1.4%) on the waiting list. The liver condition remained stable or improved in 35 (49.3%), and the neurological status showed improvement in 11 (34.4%) of the 32 patients who had neurological involvement. Conclusions: This is the biggest cohort to be reported from the Middle East. WD presentation and outcome of WD are very diverse, and its diagnosis still depends on clinical, laboratory, and radiological evidence of abnormal copper metabolism. WD should be considered in patients of any age with obscure hepatic and/or neurological abnormalities.",abdominal distension;adult;akinesia;anorexia;ascites;body mass;clinical feature;confusion;dyskinesia;dystonia;electronic medical record;erythema;family history;fatigue;female;follow up;hepatic encephalopathy;hepatomegaly;human;human tissue;jaundice;leg edema;liver cell carcinoma;liver transplantation;major clinical study;male;medical record review;mental disease;mortality;motor dysfunction;outcome assessment;priority journal;retrospective study;review;Saudi Arabia;sclera disease;splenomegaly;tertiary health care;tremor;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Fadda, M. A.;Quaiz, M. A.;Ashgar, H. A.;Kahtani, K. A.;Helmy, A.;Benmousa, A. A.;Abdulla, M.;Peedikayil, M.",2012,November-December,http://dx.doi.org/10.5144/0256-4947.2012.623,0,1,
1588,Wilson's Disease-Treatment of Psychiatric Manifestations in Pregnancy,,adult;article;auditory hallucination;bipolar disorder/dt [Drug Therapy];brain level;case report;copper blood level;female;human;hypertransaminasemia/dt [Drug Therapy];hyperuricemia/dt [Drug Therapy];liver failure;mental instability;monotherapy;paranoia;pregnancy;prophylaxis;puerperal psychosis/co [Complication];puerperal psychosis/dt [Drug Therapy];puerperal psychosis/pc [Prevention];treatment outcome;visual hallucination;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];lithium/cr [Drug Concentration];lithium/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];ursodeoxycholic acid/cb [Drug Combination];ursodeoxycholic acid/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Rich, A. M.;Lajoie, T. M.",2012,March,http://dx.doi.org/10.1016/j.psym.2012.01.002,0,0,
1589,Golden ring in eyes: All that glitters is not gold!,,adult;article;ascites;case report;clinical examination;cornea lesion/di [Diagnosis];foot edema;human;liver cirrhosis;male;portal hypertension;priority journal;slit lamp;splenomegaly;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];diuretic agent/cb [Drug Combination];diuretic agent/dt [Drug Therapy];propranolol/cb [Drug Combination];propranolol/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Tayde, P.;Wanjari, A.;Kokate, V.",2012,April,http://dx.doi.org/10.1016/j.amjmed.2011.10.020,0,0,
1590,Copper overload in 6-year-old twins,,article;case report;child;energy drink;fatigue;hepatosplenomegaly;human;human tissue;intoxication;laboratory test;liver biopsy;liver failure/si [Side Effect];liver failure/su [Surgery];liver fibrosis;liver transplantation;male;preschool child;priority journal;treatment outcome;twins;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/to [Drug Toxicity];trientene/ae [Adverse Drug Reaction];trientene/dt [Drug Therapy];unclassified drug;zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Bartlett, M. G.;Erickson, N. I.",2012,December,http://dx.doi.org/10.1097/MPG.0b013e3182311a24,0,0,
1591,Urinary copper excretion before and after oral intake of d-penicillamine in parents of patients with Wilson's disease,"Background: Urinary copper excretion higher than 100 mug/24. h is useful for diagnosing Wilson's disease. d-Penicillamine challenge test may produce higher levels than 1400 mug/24. h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering d-penicillamine to the parents of Wilson's disease patients. Methods: Fifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1. g d-penicillamine. Results: Serum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8 x 27.8. mg%; 71.4 x 88.0 mug%; p<= 0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2 x 18.7 mug/24. h, p= 0.01), but did not differ between the genders after d-penicillamine (521.7 x 525.3, range 31.6-1085.1 mug/24. h, p= 0.8). Conclusions: The mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after d-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after d-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease. © 2011 Editrice Gastroenterologica Italiana S.r.l.",ATP7B heterozygotes;Cupriuresis;Hepatolenticular degeneration;adult;article;ceruloplasmin blood level;clinical article;controlled study;diagnostic accuracy;diagnostic test accuracy study;drug excretion;father;female;heterozygote;human;male;mother;parent;priority journal;sex difference;urinary copper excretion;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/cr [Drug Concentration];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology],"Vieira, J.;Oliveira, P. V.;Juliano, Y.;Warde, K. R. J.;Deguti, M. M.;Barbosa, E. R.;Carrilho, F. J.;Cancado, E. L. R.",2012,April,http://dx.doi.org/10.1016/j.dld.2011.11.001,0,0,
1592,Wilson's disease: An uncommon presentation,"Wilson's disease (WD), also known as hepatolenticular degeneration, is an inborn error of metabolism inherited as an autosomal recessive trait, characterized by toxic accumulation of copper in the body, particularly liver, brain and eyes. In children,WD presents more often with hepatic manifestations like acute hepatitis,cirrhosis of liver or liver failure.We present an unusual presentation of WD in a 15 years old male child who presented with neuropsychiatric manifestations without hepatic involvement.",Autosomal recessive;Hepatolenticular degeneration;Neuropsychiatric manifestations;Wilson's disease;adolescent;article;blood cell count;body posture;case report;drug response;drug substitution;drug withdrawal;dysphagia;dystonia;eye movement;general condition deterioration;human;hypersalivation;liver function test;male;motor dysfunction;muscle atrophy;nuclear magnetic resonance imaging;patient compliance;slit lamp;speech disorder;tendon reflex;vital sign;walking difficulty;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Alam, B.;Biswas, S.;Maria, M.;Rahman, A.;Rahman, H.;Das, P. P.;Rahman, S.;Kabir, K.",2012,,,0,0,
1593,Surgery in a Patient with Liver Disease,"Surgery is often needed in patients with concurrent liver disease. The multiple physiological roles of the liver places these patients at an increased risk of morbidity and mortality. Diseases necessitating surgery like gallstones and hernia are more common in patients with cirrhosis. Assessment of severity of liver dysfunction before surgery is important and the risk benefit of the procedure needs to be carefully assessed. The disease severity may vary from mild transaminase rise to decompensated cirrhosis. Surgery should be avoided if possible in the emergency setting, in the setting of acute and alcoholic hepatitis, in a patient of cirrhosis who is child class C or has a MELD score more than 15 or any patient with significant extrahepatic organ dysfunction. In this subset of patients, all possible means to manage these patients conservatively should be attempted. Modified Child-Pugh scores and model for end-stage liver disease (MELD) scores can predict mortality after surgery fairly reliably including nonhepatic abdominal surgery. Pre-operative optimization would include control of ascites, correction of electrolyte imbalance, improving renal dysfunction, cardiorespiratory assessment, and correction of coagulation. Tests of global hemostasis like thromboelastography and thrombin generation time may be more predictive of the risk of bleeding compared with the conventional tests of coagulation in patients with cirrhosis. Correction of international normalized ratio with fresh frozen plasma does not necessarily mean reduction of bleeding risk and may increase the risk of volume overload and lung injury. International normalized ratio liver may better reflect the coagulation status. Recombinant factor VIIa in patients with cirrhosis needing surgery needs further study. Intra-operatively, safe anesthetic agents like isoflurane and propofol with avoidance of hypotension are advised. In general, nonsteroidal anti-inflammatory drug (NSAIDs) and benzodiazepines should not be used. Intra-abdominal surgery in a patient with cirrhosis becomes more challenging in the presence of ascites, portal hypertension, and hepatomegaly. Uncontrolled hemorrhage due to coagulopathy and portal hypertension, sepsis, renal dysfunction, and worsening of liver failure contribute to the morbidity and mortality in these patients. Steps to reduce ascitic leaks and infections need to be taken. Any patient with cirrhosis undergoing major surgery should be referred to a specialist center with experience in managing liver disease. © 2012 INASL.",Anesthesia;Child-Pugh score;Cirrhosis;Coagulopathy;Hepatic;alcohol liver disease;anesthesia induction;ascites;autoimmune liver disease/dt [Drug Therapy];bariatric surgery;bleeding/dt [Drug Therapy];blood clotting disorder/dt [Drug Therapy];cardiovascular function;cardiovascular surgery;cellulitis/dt [Drug Therapy];cholecystectomy;cryoprecipitate;dose response;drug contraindication;drug dose reduction;drug metabolism;functional assessment;gallstone/su [Surgery];hemodynamic monitoring;hemoperitoneum/dt [Drug Therapy];hemostasis;hepatomegaly;hernioplasty;human;inguinal hernia/su [Surgery];international normalized ratio;liver cirrhosis;liver disease;liver failure;loading drug dose;morbid obesity/su [Surgery];oral bleeding/dt [Drug Therapy];perioperative complication/co [Complication];perioperative complication/dt [Drug Therapy];perioperative complication/th [Therapy];peroperative care;plasma transfusion;portal hypertension;portal vein thrombosis/dt [Drug Therapy];postoperative care;preoperative evaluation;priority journal;protein deficiency/th [Therapy];repeated drug dose;respiratory function;review;risk assessment;surgical approach;surgical mortality;surgical risk;thrombin time;thrombocyte transfusion;thrombocytopenia/co [Complication];thrombocytopenia/th [Therapy];thromboelastography;umbilical hernia/su [Surgery];vitamin K deficiency/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];anesthetic agent/ih [Inhalational Drug Administration];antibiotic agent/dt [Drug Therapy];antifibrinolytic agent/dt [Drug Therapy];atracurium/pk [Pharmacokinetics];cisatracurium/pk [Pharmacokinetics];desflurane/pk [Pharmacokinetics];desmopressin/ct [Clinical Trial];desmopressin/dt [Drug Therapy];desmopressin/na [Intranasal Drug Administration];isoflurane/pk [Pharmacokinetics];low molecular weight heparin/ct [Clinical Trial];low molecular weight heparin/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];propofol;recombinant blood clotting factor 7a/do [Drug Dose];recombinant blood clotting factor 7a/dt [Drug Therapy];sevoflurane/pk [Pharmacokinetics];steroid/dt [Drug Therapy];tranexamic acid/do [Drug Dose];tranexamic acid/dt [Drug Therapy];vitamin K group/dt [Drug Therapy];vitamin K group/iv [Intravenous Drug Administration];vitamin K group/po [Oral Drug Administration],"Rai, R.;Nagral, S.;Nagral, A.",2012,September,http://dx.doi.org/10.1016/j.jceh.2012.05.003,0,0,
1594,"Subdural hematoma in a young woman with an ""old"" brain",,adult;case report;craniotomy;fatty liver;female;follow up;headache;hemiparesis;human;human tissue;letter;liver biopsy;liver fibrosis;nuclear magnetic resonance imaging;slurred speech;subdural hematoma/di [Diagnosis];subdural hematoma/et [Etiology];subdural hematoma/su [Surgery];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy],"Masciullo, M.;Mattogno, P. P.;Modoni, A.;Silvestri, G.;de Bonis, P.",2012,December,http://dx.doi.org/10.1007/s13760-012-0054-9,0,0,
1595,"Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium","Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system. © 2012 International Life Sciences Institute.",Copper;Iron;Limbic system;Selenium;Zinc;amygdaloid nucleus;attention deficit disorder/et [Etiology];brain function;cingulate gyrus;copper deficiency;copper excess;copper metabolism;corpus striatum;depression/et [Etiology];diabetes mellitus;emotion;epilepsy/et [Etiology];evoked response;Friedreich ataxia/et [Etiology];human;Huntington chorea/et [Etiology];hypothalamus;iron absorption;iron binding capacity;iron deficiency;iron excess;iron metabolism;iron transport;Lewy body/et [Etiology];Menkes syndrome/et [Etiology];myelination;neurochemistry;neurologic disease;neurotransmission;nucleus accumbens;nutritional disorder;oligodendroglia;orbital cortex;oxidative stress;parahippocampal gyrus;Parkinson disease/et [Etiology];prefrontal cortex;pregnancy;protein expression;review;reward;schizophrenia/et [Etiology];selenium deficiency;substantia nigra;Wilson disease/et [Etiology];zinc deficiency;zinc excess;zinc metabolism;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];selenium/ec [Endogenous Compound];selenoprotein P/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Torres-Vega, A.;Pliego-Rivero, B. F.;Otero-Ojeda, G. A.;Gomez-Olivan, L. M.;Vieyra-Reyes, P.",2012,December,http://dx.doi.org/10.1111/j.1753-4887.2012.00521.x,0,0,
1596,Role of the human high-affinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy,"The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation. © 2012 AACR.",anemia/si [Side Effect];apoptosis;binding affinity;bone marrow suppression/si [Side Effect];chelation therapy;chemosensitization;drug efficacy;drug safety;drug sensitivity;drug uptake;homeostasis;human;nonhuman;ovary cancer/dt [Drug Therapy];priority journal;protein analysis;protein binding;protein cross linking;protein degradation;protein domain;protein expression;protein function;protein processing;protein synthesis;review;transcription regulation;upregulation;Wilson disease;carboplatin/ae [Adverse Drug Reaction];carboplatin/ct [Clinical Trial];carboplatin/cb [Drug Combination];carboplatin/dt [Drug Therapy];carrier protein/ec [Endogenous Compound];cisplatin/dt [Drug Therapy];copper;copper transporter 1/ec [Endogenous Compound];glutamate cysteine ligase/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];platinum complex/ct [Clinical Trial];platinum complex/dt [Drug Therapy];pregnancy specific beta1 glycoprotein/ec [Endogenous Compound];thiomolybdic acid;trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];unclassified drug;zinc finger protein/ec [Endogenous Compound],"Kuo, M. T.;Fu, S.;Savaraj, N.;Chen, H. H. W.",2012,15 Sep,http://dx.doi.org/10.1158/0008-5472.CAN-12-0888,0,0,
1597,Wilson disease: Canadian perspectives on presentation and outcomes from an adult ambulatory setting,"BACKGROUND: Wilson disease (WD) is a rare disorder of copper metabolism. OBJECTIVE: To describe the authors' clinical experience with a cohort of 48 adult patients followed in an ambulatory setting. METHODS: A retrospective chart review of patients with a diagnosis of WD was performed. RESULTS: Fifty-nine charts were identified and 11 were excluded on further review. At diagnosis, 14 patients were asymptomatic, with 13 hepatic, 15 neurological and six mixed hepatic/neurological presentations. Ceruloplasmin levels were low (<0.20 g/L) in 94%, and 24 h urinary copper levels high (>0.60 mumol/L) in 95% of cases. D-penicillamine was the most common initial therapy (48%), with zinc the most common at review (65%). Overall, biopsy and ultrasound reports documented cirrhosis in 53%. Portal hypertension, defined as splenomegaly (>12.0 cm), reversed portal venous flow on ultrasound or varices/gastropathy on endoscopy was seen in 63%. At last review, 39% had elevated aspartate aminotransferase (>34 U/L) and/or alanine aminotransferase levels (>40 U/L). One death and one transplant occurred, while three patients had encephalopathy, two became jaundiced, two developed ascites and one experienced variceal bleed. Of 21 neurological presenting patients, 14 improved compared with baseline, with four making almost complete recovery. Eleven patients experienced documented episodes of neurological decline, including four with non-neurological presentation. Diagnostic magnetic resonance imaging showed basal ganglia (64%), brainstem (64%) abnormalities and atrophy (36%); follow-up showed basal ganglia lesions (50%) and atrophy (55%). CONCLUSION: WD is a diverse chronic disease with generally favourable outcomes for patients who respond to initial therapy, which can be managed predominantly in an ambulatory setting. ©2012 Pulsus Group Inc. All rights reserved.",Ceruloplasmin;Hepatolenticular degeneration;Movement disorders;Wilson disease;adolescent;adult;ambulatory care;article;ceruloplasmin blood level;child;cohort analysis;human;liver cirrhosis;major clinical study;preschool child;priority journal;retrospective study;school child;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Moores, A.;Fox, S. H.;Lang, A. E.;Hirschfield, G. M.",2012,June,,0,1,
1598,Clinical efficacy and safety of Chinese herbal medicine for Wilson's disease: A systematic review of 9 randomized controlled trials,"Wilson's disease is an autosomal recessive disorder of copper metabolism. Despite being treatable, there is no universally accepted treatment regimen. Currently, various Chinese herbal medicines (CHMs) are widely used in the treatment of Wilson's disease in China, but there is a lack of reliable scientific evidence for the effectiveness of such therapies. The objective of this systematic review is to assess the clinical efficacy and safety of CHM as an alternative or/and adjuvant therapy for Wilson's disease. A systematic literature search in different medical databases was performed to identify randomized controlled trials comparing CHM as monotherapy or CHM as adjuvant therapy with western conventional medical therapy in the treatment of Wilson's disease. A total of 687 participants were included in nine eligible studies. The main findings are that CHM as monotherapy or adjuvant therapy for Wilson's disease may be able to improve the clinical symptoms, to promote the urinary copper excretion, to ameliorate liver function and/or liver cirrhosis, and has fewer adverse effects in comparison with western conventional medication. Furthermore, CHM generally appeared to be safe and well tolerated in patients with Wilson's disease. However, the evidence presented in this review are insufficient to warrant a clinical recommendation due to the generally low methodological quality of the included studies. In conclusion, CHM seems to be beneficial and safe for Wilson's disease, but high-quality evidences are still needed to further evaluate this therapy. Therefore, additional well-designed, randomized, placebo-controlled clinical trials are needed. © 2011 Elsevier Ltd.",Chinese herbal medicine;Systematic review;Wilson's disease;adjuvant therapy;Chinese medicine;drug efficacy;drug safety;drug tolerability;gastrointestinal symptom/si [Side Effect];herbal medicine;human;liver cirrhosis;liver function;monotherapy;outcome assessment;patient compliance;randomized controlled trial (topic);review;side effect/si [Side Effect];thrombocyte count;urinary copper excretion;urinary excretion;Wilson disease/dt [Drug Therapy];chaihuang gandou pulvis/ae [Adverse Drug Reaction];chaihuang gandou pulvis/ct [Clinical Trial];chaihuang gandou pulvis/cm [Drug Comparison];chaihuang gandou pulvis/dt [Drug Therapy];edetate calcium disodium/ct [Clinical Trial];edetate calcium disodium/cm [Drug Comparison];edetate calcium disodium/dt [Drug Therapy];gandou/ae [Adverse Drug Reaction];gandou/ct [Clinical Trial];gandou/cb [Drug Combination];gandou/cm [Drug Comparison];gandou/dt [Drug Therapy];gandouling/ae [Adverse Drug Reaction];gandouling/ct [Clinical Trial];gandouling/cb [Drug Combination];gandouling/cm [Drug Comparison];gandouling/dt [Drug Therapy];herbaceous agent/ae [Adverse Drug Reaction];herbaceous agent/ct [Clinical Trial];herbaceous agent/cb [Drug Combination];herbaceous agent/cm [Drug Comparison];herbaceous agent/dt [Drug Therapy];herbaceous agent/iv [Intravenous Drug Administration];herbaceous agent/po [Oral Drug Administration];oxymatrine/ct [Clinical Trial];oxymatrine/cb [Drug Combination];oxymatrine/cm [Drug Comparison];oxymatrine/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/cb [Drug Combination];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];ruanjiantangjiang/ct [Clinical Trial];ruanjiantangjiang/cb [Drug Combination];ruanjiantangjiang/cm [Drug Comparison];ruanjiantangjiang/dt [Drug Therapy];shuganlidanpaidu/ae [Adverse Drug Reaction];shuganlidanpaidu/ct [Clinical Trial];shuganlidanpaidu/cm [Drug Comparison];shuganlidanpaidu/dt [Drug Therapy];succimer/ae [Adverse Drug Reaction];succimer/ct [Clinical Trial];succimer/cb [Drug Combination];succimer/cm [Drug Comparison];succimer/dt [Drug Therapy];tiopronin/ct [Clinical Trial];tiopronin/cb [Drug Combination];tiopronin/cm [Drug Comparison];tiopronin/dt [Drug Therapy];unclassified drug;unithiol/ct [Clinical Trial];unithiol/cb [Drug Combination];unithiol/cm [Drug Comparison];unithiol/dt [Drug Therapy];zinc sulfate/ct [Clinical Trial];zinc sulfate/cb [Drug Combination];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy],"Wang, Y.;Xie, C. L.;Fu, D. L.;Lu, L.;Lin, Y.;Dong, Q. Q.;Wang, X. T.;Zheng, G. Q.",2012,June,http://dx.doi.org/10.1016/j.ctim.2011.12.004,0,0,
1599,Three cases of Wilson's disease masquerading as childhood muscular dystrophy,"Various authors have reported that Wilson's disease in India may masquerade as childhood muscular dystrophy. It is a potentially treatable condition and therefore, early recognition is important and every suspected patient with childhood muscular dystrophy should be examined for the presence of Kayser-Fleischer ring in the cornea and also be screened for copper profile. We report three such cases who were initially diagnosed as childhood muscular dystrophy but on subsequent screening turned out to be cases of Wilson's disease. © 2012 Elsevier GmbH.",Childhood muscular dystrophy;Copper profile;Wilson's disease;adolescent;article;blood analysis;case report;child;consanguineous marriage;differential diagnosis;eye examination;human;India;male;Mini Mental State Examination;muscle atrophy;muscle biopsy;muscle hypertrophy;muscle weakness;muscular dystrophy/di [Diagnosis];priority journal;school child;screening test;slit lamp;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatine kinase/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Bhattacharyya, K. B.;Basu, S.;Chakravarty, A.",2012,July,http://dx.doi.org/10.1016/j.baga.2012.02.002,0,0,
1600,Wilson disease in a Nigerian child: A case report,"Introduction. Wilson disease is rarely reported among African children. This report describes the second case report of a Nigerian child with Wilson disease in three decades. Case presentation. An eight-year-old African boy presented with generalized oedema and ascites and proteinuria. Over the next three weeks he developed conjugated hyperbilirubinaemia, severe coagulopathy and prominent extrapyramidal features consisting of rigidity, tremors at rest and in action, shuffling gait, slurred speech and emotional lability. Slit-lamp examination of his eyes revealed Kayser-Fleischer rings and sunflower cataracts. His serum caeruloplasmin level was 5mg/dL. Using the scoring system proposed by the 8<sup>th</sup> International Meeting of Wilson Disease and Menkes Disease, a diagnosis of Wilson disease was made. Conclusions: Wilson disease does occur in African children, although the diagnosis is rarely made. A diagnosis of Wilson disease should be entertained in the evaluation of African children presenting with liver dysfunction and/or extrapyramidal neurological features. © 2012 Esezobor et al.; licensee BioMed Central Ltd.",article;ascites/di [Diagnosis];blood clotting disorder;case report;cataract/di [Diagnosis];ceruloplasmin blood level;child;clonic seizure/dt [Drug Therapy];creatinine urine level;diet restriction;disease severity;drowsiness;dysarthria;echography;extrapyramidal symptom;gait disorder;gallbladder;generalized edema/dt [Drug Therapy];grand mal seizure/dt [Drug Therapy];hepatomegaly/di [Diagnosis];human;hyperbilirubinemia;international normalized ratio;liver dysfunction;liver function test;male;mental instability;muscle rigidity;Nigeria;priority journal;protein restriction;protein urine level;proteinuria;rare disease;school child;scoring system;slit lamp;slurred speech;swelling;tremor;urine volume;walking;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper;creatinine/ec [Endogenous Compound];diazepam/dt [Drug Therapy];furosemide/dt [Drug Therapy];lactulose;neomycin;phenobarbital/dt [Drug Therapy];pyridoxine;spironolactone/dt [Drug Therapy];trihexyphenidyl;vitamin K group;zinc,"Esezobor, C. I.;Banjoko, N.;Rotimi-Samuel, A.;Lesi, F. E. A.",2012,,http://dx.doi.org/10.1186/1752-1947-6-200,0,0,
1601,From suspicion of liver metastases to the diagnosis of Wilson disease in a patient with seminoma,"Wilson disease is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and cornea due to inadequate biliary copper excretion. It should be considered especially in young patients who have findings of liver disease with unexplained etiology. Clinical presentation of the disease can be variable, and different types of parenchymal changes of the liver can be seen on imaging modalities. Multiple nodular lesions mimicking metastases can be detected. This condition can obligate physicians to screen for a malignant disease. Moreover, it may cause misdiagnosis as advanced stage of disease when coexistent with a malignancy. The coexistence of Wilson disease with some malignant diseases has been reported; however, coexistence with seminoma was not reported before. Approximately 40% of testicular cancers are pure seminoma. Liver metastases are rare in seminoma. In this article, a case of Wilson cirrhosis is reported. The patient was first followed with diagnosis of seminoma with suspicion of liver metastases.",Liver metastases;Nodular lesions;Seminoma;Wilson disease;adult;article;aspartate aminotransferase blood level;aspiration biopsy;cancer combination chemotherapy;case report;chronic liver disease;computer assisted tomography;echography;follow up;histopathologic skin reaction;human;leukocyte;liver biopsy;liver cirrhosis;liver metastasis;male;multiple cycle treatment;prothrombin time;seminoma/dt [Drug Therapy];splenomegaly;thrombocyte;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];alpha fetoprotein/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];bleomycin/cb [Drug Combination];bleomycin/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chorionic gonadotropin beta subunit/ec [Endogenous Compound];cisplatin/cb [Drug Combination];cisplatin/dt [Drug Therapy];copper;etoposide/cb [Drug Combination];etoposide/dt [Drug Therapy];gamma glutamyltransferase/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Aksakal, G.;Songur, Y.;Isler, M.;Akin, M.",2012,April,http://dx.doi.org/10.4318/tjg.2012.0335,0,0,
1602,Metal element excretion in 24-h urine in patients with wilson disease under treatment of D-penicillamine,"Wilson disease is an inherited autosomal recessive disorder causing copper accumulation and consequent toxicity. D-Penicillamine, a potent metal chelator, is an important therapy for Wilson disease. To investigate the changes of metal elements under the treatment of D-penicillamine, we determined the levels of Cu, Zn, Mg, Ca, Fe, Se, Mn, Pb, Hg, Cd, As, Tl, and Al by ICP-MS in 24-h urine of 115 Wilson disease patients who had received treatment with D-penicillamine for 1 month to 22 years at maintenance doses, as well as 115 age-matched, healthy controls. The levels of Cu, Mg, Ca, Zn, Hg, Pb, Tl, Cd, and Mn in the 24-h urine of the cases were significantly higher than those of the controls (P<0.05), and the observed increases in the levels of Mg, Ca, and Zn were directly correlated with the treatment duration with Pearson Correlation Coefficient (R) of 0.356 (Mg), 0.329 (Ca), and 0.313 (Zn), respectively (P<0.05). On the other hand, the levels of Al and As in the 24-h urine were lower than those of the controls (P<0.05) and were negatively correlated with the treatment time with R of -0.337 (Al) and -0.398 (As), respectively, (P<0.05). Thus, this study indicates that the levels of metal elements may be altered in patients with Wilson disease under the treatment of D-penicillamine. © Springer Science+Business Media, LLC 2011.",24-h urine;As;Ca;Cu;D-Penicillamine;icp-ms;Metal elements;Wilson disease;Zn;article;clinical feature;controlled study;disease association;female;human;maintenance therapy;major clinical study;male;mass spectrometry;outcome assessment;treatment duration;urinalysis;urinary excretion;urine level;Wilson disease/dt [Drug Therapy];aluminum;arsenic;cadmium;calcium;copper;iron;lead;magnesium;manganese;mercury;penicillamine/dt [Drug Therapy];selenium;titanium;zinc,"Huang, L.;Zhang, J.;Liu, X.;Zhang, Y.;Jiao, X.;Yu, X.",2012,May,http://dx.doi.org/10.1007/s12011-011-9250-3,0,0,
1603,Impact of the discovery of human zinc deficiency,,blindness/pc [Prevention];cellular immunity;chronic inflammation;clinical feature;clinical trial (topic);common cold/dt [Drug Therapy];dwarfism;editorial;enzyme activity;human;immune system;mortality;nonhuman;oxidative stress;protein function;retina macula age related degeneration/dt [Drug Therapy];risk factor;signal transduction;Wilson disease/dt [Drug Therapy];zinc deficiency/et [Etiology];zinc deficiency/si [Side Effect];immunoglobulin enhancer binding protein/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];STAT4 protein/ec [Endogenous Compound];thymidine kinase/ec [Endogenous Compound];thymulin/ec [Endogenous Compound];transcription factor T bet/ec [Endogenous Compound];zinc/ct [Clinical Trial];zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy];zinc transporter/ec [Endogenous Compound],"Prasad, A. S.",2012,September,,0,0,
1604,Dystonia,,abdominal cramp/si [Side Effect];article;bedtime dosage;blepharospasm/dt [Drug Therapy];blepharospasm/su [Surgery];brain radiography;cervical dystonia/su [Surgery];clinical feature;confusion/si [Side Effect];continuous infusion;depression/si [Side Effect];drowsiness/si [Side Effect];drug dose escalation;drug dose titration;dysarthria/co [Complication];dyskinesia/si [Side Effect];dysphagia/co [Complication];dystonia/di [Diagnosis];dystonia/dt [Drug Therapy];dystonia/et [Etiology];dystonia/si [Side Effect];dystonia/su [Surgery];dystonia/th [Therapy];DYT1 gene;DYT6 gene;essential tremor;focal dystonia/dt [Drug Therapy];gene;gene deletion;generalized dystonia/dt [Drug Therapy];genetic screening;hallucination/si [Side Effect];hemidystonia;human;infection/dt [Drug Therapy];involuntary movement;liquorrhea/dt [Drug Therapy];low drug dose;Meige syndrome;memory disorder/si [Side Effect];multifocal dystonia;muscle resection;muscle weakness/co [Complication];mutational analysis;myoclonus dystonia/dt [Drug Therapy];narcolepsy/dt [Drug Therapy];nausea/si [Side Effect];nephritis/si [Side Effect];neuropathology;neurosurgery;nuclear magnetic resonance imaging;onset age;paresthesia/co [Complication];parkinsonism/si [Side Effect];physiotherapy;priority journal;respiration depression/si [Side Effect];sedation;segmental dystonia/dt [Drug Therapy];side effect/si [Side Effect];tardive dyskinesia/si [Side Effect];transcranial magnetic stimulation;unspecified side effect/si [Side Effect];urine retention/si [Side Effect];urticaria/si [Side Effect];Wilson disease/dt [Drug Therapy];writer's cramp;baclofen/ae [Adverse Drug Reaction];baclofen/do [Drug Dose];baclofen/dt [Drug Therapy];baclofen/tl [Intrathecal Drug Administration];baclofen/po [Oral Drug Administration];benzatropine/dt [Drug Therapy];benzatropine mesilate/dt [Drug Therapy];biperiden/dt [Drug Therapy];carbidopa plus levodopa/ae [Adverse Drug Reaction];carbidopa plus levodopa/do [Drug Dose];carbidopa plus levodopa/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];cholinergic receptor blocking agent/po [Oral Drug Administration];clonazepam/dt [Drug Therapy];clozapine/dt [Drug Therapy];cyclobenzaprine/dt [Drug Therapy];diazepam/dt [Drug Therapy];diphenhydramine/dt [Drug Therapy];diphenhydramine/iv [Intravenous Drug Administration];dopamine receptor blocking agent/ae [Adverse Drug Reaction];dopamine receptor blocking agent/dt [Drug Therapy];etiracetam/dt [Drug Therapy];lorazepam/dt [Drug Therapy];metaxalone/dt [Drug Therapy];neuroleptic agent/dt [Drug Therapy];oxybate sodium/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];profenamine/dt [Drug Therapy];pyridostigmine/cb [Drug Combination];pyridostigmine/dt [Drug Therapy];reserpine/dt [Drug Therapy];risperidone/dt [Drug Therapy];tetrabenazine/ae [Adverse Drug Reaction];tetrabenazine/dt [Drug Therapy];tizanidine/dt [Drug Therapy];topiramate/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trihexyphenidyl/ae [Adverse Drug Reaction];trihexyphenidyl/cb [Drug Combination];trihexyphenidyl/do [Drug Dose];trihexyphenidyl/dt [Drug Therapy];unindexed drug;valproic acid/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Shanker, V.;Bressman, S.",2012,,http://dx.doi.org/10.1007/978-1-60327-120-2_3,0,0,
1605,Liver Disease in Pregnancy,"Changes in the liver biochemical profile are normal in pregnancy. However, up to 3% to 5% of all pregnancies are complicated by liver dysfunction. It is important that liver disease during pregnancy is recognized because early diagnosis may improve maternal and fetal outcomes, with resultant decreased morbidity and mortality. Liver diseases that occur in pregnancy can be divided into 3 different groups: liver diseases that are unique to pregnancy, liver diseases that are not unique to pregnancy but can be revealed or exacerbated by pregnancy, and liver diseases that are unrelated to but occur coincidentally during pregnancy. © 2012 Elsevier Inc.",Liver biochemical profile;Liver disease;Pregnancy;alanine aminotransferase blood level;alkaline phosphatase blood level;antiviral therapy;aspartate aminotransferase blood level;autoimmune hepatitis;bile acid blood level;Budd Chiari syndrome;ceruloplasmin blood level;cholesterol blood level;copper blood level;decompensated liver cirrhosis;disease association;disease exacerbation;disseminated intravascular clotting;drug safety;drug use;echography;eclampsia and preeclampsia;fatty liver;fetus outcome;fibrinogen blood level;gallstone;gamma glutamyl transferase blood level;gestational age;HELLP syndrome;hemoglobin blood level;hepatitis B;hepatitis C;human;hyperemesis gravidarum;immunosuppressive treatment;intrahepatic cholestasis;leukocyte count;liver biopsy;liver cirrhosis;liver disease/di [Diagnosis];liver dysfunction;liver fatty degeneration;liver function test;liver graft rejection;liver toxicity;liver transplantation;nuclear magnetic resonance imaging;partial thromboplastin time;pregnancy disorder/di [Diagnosis];pregnancy outcome;primary biliary cirrhosis;primary sclerosing cholangitis;radiography;review;sepsis;third trimester pregnancy;thrombocyte;thrombocyte count;thrombocytopenia;thromboplastin time;toxic hepatitis;triacylglycerol blood level;virus hepatitis;virus transmission;Wilson disease;alanine aminotransferase;alkaline phosphatase;alpha fetoprotein;alpha globulin;aspartate aminotransferase;azathioprine;beta globulin;bile acid;blood clotting factor 5;blood clotting factor 7;blood clotting factor 8;ceruloplasmin;cholesterol;cyclosporin;fibrinogen;gamma glutamyltransferase;hemoglobin;immunoglobulin;lamivudine;mycophenolic acid 2 morpholinoethyl ester;octreotide;penicillamine;prednisone;serum albumin;tacrolimus;triacylglycerol;trientine;unindexed drug;ursodeoxycholic acid;zinc acetate,"Mufti, A. R.;Reau, N.",2012,May,http://dx.doi.org/10.1016/j.cld.2012.03.011,0,0,
1606,[Nephrotic syndrome after treatment with d-penicillamine in a pediatric patient with Wilson's disease]. [Italian],"We describe a case of nephrotic syndrome (NS) after a 7 months treatment with D-penicillamine in a 14 years old girl with Wilson's disease, with a prompt regression at the discontinuation of the drug. Kidney function, proteinuria in particular, must be always monitored during the chelating therapy, and the drug must be discontinued as soon as signs of renal injury are detected.",adolescent;article;case report;chemically induced disorder;female;human;nephrotic syndrome;time;treatment outcome;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/ad [Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];zinc acetate/ad [Drug Administration],"Farallo, M.;Amoruso, C.;Frattini, C.;Ardissino, G.;Nebbia, G.",2012,2012,,0,0,
1607,"Wilson's disease presenting with hypokalemia, hypoparathyroidism and renal failure","Wilson's disease (WD) is not as rare as once believed, and has a wide range of presentations with equally wide range of age of onset. Sometimes the primary presentation might be unusual and may require a thorough investigation to avoid a misdiagnosis. Our case presented with uncontrolled seizures, severe hypokalemia, renal failure, and hypoparathyroidism. After being diagnosed as WD and treated for the same patient made a remarkable recovery. © JAPI.",adolescent;article;case report;human;hypocalcemia/co [Complication];hypokalemia/et [Etiology];hypoparathyroidism/co [Complication];kidney failure/co [Complication];seizure/et [Etiology];treatment outcome;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];colecalciferol/ad [Drug Administration];vitamin/ad [Drug Administration];zinc acetate/ad [Drug Administration],"Ghosh, L.;Shah, M.;Patel, S.;Mannari, J.;Sharma, K.",2012,September,,0,0,
1608,Wilson disease: Why talking about it. [Italian],"Wilson disease (WD) is an inherited autosomal recessive disorder of copper metabolism characterized by progressive copper accumulation in the liver and then in other organs, such as the nervous system, eyes and kidneys. In childhood, clinical presentation of WD is usually characterized by signs of liver disease, while the typical neurological signs are rarely observed. The hepatic clinical presentation ranges widely among different settings. In Italy, the majority of the paediatric patients with WD are recruited following the detection of isolated hypertransaminasemia. Early detection of WD is desirable in order to avoid the dramatic progression of the hepatic and neurologic diseases. Unfortunately, early diagnosis is a challenging task, especially in childhood, because the conventional criteria established for adults are not always appropriate for children. The currently available drugs are D-penicillamine and zinc, which act with different mechanisms. None of the available drugs is side-effect-free. In this article the main key-points of diagnosis and management of WD in paediatric patients are discussed.",Aminotransferases;ATP7B gene;Ceruloplasmin;Cupruria;Wilson disease;article;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dm [Disease Management];autosomal recessive disorder/et [Etiology];child;clinical feature;early diagnosis;human;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/dm [Disease Management];inborn error of metabolism/et [Etiology];liver disease;liver function test;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];Wilson disease/et [Etiology];copper,"Iorio, R.;Ranucci, G.;Liccardo, D.;Puoti, M. G.;Di Dato, F.",2012,October,,0,0,
1609,Zinc as a multipurpose trace element,,Alzheimer disease/et [Etiology];apoptosis;biological functions;cardiovascular disease/et [Etiology];cell proliferation;depression/et [Etiology];diabetes mellitus/et [Etiology];DNA synthesis;editorial;enzyme activity;enzyme inhibition;health status;human;immune response;natural killer cell;neoplasm/et [Etiology];oxidative stress;pathogenesis;priority journal;protein DNA binding;transcription regulation;Wilson disease/et [Etiology];zinc deficiency;caspase;dna;metallothionein;protein p53;reactive oxygen metabolite;thymidine kinase;trace element;zinc;zinc finger protein,"Marchan, R.;Cadenas, C.;Bolt, H. M.",2012,April,http://dx.doi.org/10.1007/s00204-012-0843-1,0,0,
1610,Gross hematuria in a case of Wilson disease: Questions,,Hematuria;Renal tubular acidosis;Wilson disease;calcium urine level;case report;child;diarrhea;hematuria/di [Diagnosis];human;male;note;phase contrast microscopy;priority journal;proteinuria;school child;urinalysis;urogenital system parameters;vomiting;Wilson disease/dt [Drug Therapy];calcium/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Sinha, R.;Akhtar, S.",2012,June,http://dx.doi.org/10.1007/s00467-011-2007-6,0,0,
1611,Quality of life and psychiatric symptoms in wilson's disease: The relevance of bipolar disorders,"Introduction: Wilson's disease is an inherited disorder caused by a gene located on chromosome 13, which involved copper transportation across cell membranes. The disease can cause a reduced incorporation of copper into ceruloplasmin resulting in accumulation of this metal in the liver, central nervous system, kidneys and other organs. The objective is to define the frequencies of psychiatric disorders in WD, the amount of impairment of Quality of Life [QoL] in patients with WD and the relevance of the psychiatric disorders in the QoL of people suffering by WD. Methods: This is a systematic review. The search of the significant articles was carried out in PubMed using specific key words. Results: Such other neurological diseases, WD is characterized by chronic course and need of treatments, impairment of functional outcomes and high frequency of psychiatric symptoms, although a specific association between Bipolar Disorders and WD was recently found. Despite this, since today few studies are carried on WD patients' quality of life related to psychiatric symptoms. Some new reports showed a link between presence of Bipolar Disorders diagnosis, cerebral damage and low Qol. Conclusion: Prospective studies on large cohorts are required to establish the effective impact of psychiatric disorders comorbidity, particularly Bipolar Disorders, on quality of life in WD and to clarify the causal link between brain damage, psychiatric disorders and worsening of QoL. © Carta et al.",Bipolar disorders;Copper;Psychiatric symptoms;Quality of life;Wilson's disease;anxiety disorder;article;behavior disorder/dt [Drug Therapy];behavior disorder/ep [Epidemiology];bipolar disorder/ep [Epidemiology];brain damage;clinical feature;cognitive defect;comorbidity;depression/ep [Epidemiology];disease association;disease duration;disease severity;Hamilton scale;human;hypomania;life satisfaction;mania/dt [Drug Therapy];Mini Mental State Examination;mood disorder/dt [Drug Therapy];motor dysfunction/dt [Drug Therapy];neurologic disease/dt [Drug Therapy];nonhuman;outcome assessment;oxidative stress;personality disorder;psychosis/dt [Drug Therapy];psychosis/ep [Epidemiology];seizure/dt [Drug Therapy];Short Form 36;systematic review;treatment indication;wellbeing;Wilson disease/dm [Disease Management];clozapine;copper/ec [Endogenous Compound];lithium/dt [Drug Therapy];mood stabilizer/dt [Drug Therapy];neuroleptic agent;olanzapine;penicillamine/dt [Drug Therapy];quetiapine;tetrathiomolybdic acid/dt [Drug Therapy],"Carta, M. G.;Mura, G.;Sorbello, O.;Farina, G.;Demelia, L.",2012,,http://dx.doi.org/10.2174/1745017901208010102,0,0,
1612,Acute extrapyramidal syndrome and seizures as heralding manifestation of Wilson disease,,adult;akinesia;anticonvulsant therapy;apathy;case report;ceruloplasmin blood level;clinical feature;copper blood level;dystonia;female;human;irritability;letter;mental instability;nuclear magnetic resonance imaging;slit lamp;tonic clonic seizure/dt [Drug Therapy];ultrasound;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phenytoin/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Verma, R.;Patil, T. B.;Lalla, R. S.",2012,May-June,http://dx.doi.org/10.4103/0028-3886.98547,0,0,
1613,Ocular signs in Wilson disease,,aqueous humor;article;autosomal recessive disorder;case report;cataract;copper metabolism;ferritin blood level;fever;human;hyperferritinemia;keratoconus;liver dysfunction;male;primary biliary cirrhosis;rigidity;slit lamp;sunflower cataract;Wilson disease;ferritin/ec [Endogenous Compound];penicillamine,"Amalnath, D. S.;Subrahmanyam, D. K. S.",2012,July-September,http://dx.doi.org/10.4103/0972-2327.99716,0,0,
1614,[Wilson disease as the significant risk factor of surgical treatment--clinical case report]. [Polish],"Wilson Disease (W ) is a rare inborn disorder of cooper metabolism. In approximately 40% of cases signs and symptoms of abnormal liver functions are observed due to hepatic inflammation, cirrhosis or insufficiency. The mainstay treatment is the conservative treatment with zinc (eg Zincteral) or penicillamine. The Authors present a patient with WD who underwent surgery because of an advanced rectal prolapse (laparotomy, rectal mobilization, rectopexy, the partial sigmoid colon resection with the primary anastomosis). The postoperative course was complicated by anastomotic leakage and a subsequent diffuse peritonitis. The patient required relaparotomy and three weeks treatment in the intensive therapy unit. The Authors consider the WD as a significant risk factor for surgical patients. Surgical treatment of patients with WD should be least invasive.",anastomosis leakage/et [Etiology];article;case report;drug contraindication;female;human;laparotomy/ae [Adverse Drug Reaction];peritonitis/et [Etiology];rectum prolapse/et [Etiology];rectum prolapse/su [Surgery];reoperation;risk factor;Wilson disease/co [Complication];Wilson disease/su [Surgery],"Bielecki, K.;Zlotorowiacz, M.;Zielinska-Borkowska, U.;Tarnowski, W.",2012,,,0,0,
1615,Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms,"Background & Aims Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD. Methods In 56 patients withWD(29men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5+/-12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1beta, IL-2, IL-6, IL-10, and TNF-alpha) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals. Results WD patients had a significantly lower TAC (p< 0.00001), lower IL-10 levels (p=0.039), as well as both higher IL-1beta (p=0.019) and IL-6 (p=0.005) levels compared to the control subjects. TNF-alpha, hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological form of WD had a significantly lower TAC than those with the hepatic form (p<0.001). In addition, the lower TAC was associated with the severity of the neurological symptoms (p=0.02). No relationship between the inflammatory parameters and clinical symptoms was found. Conclusions Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients. © SSIEM and Springer 2011.",adolescent;adult;article;ATP7B gene;clinical feature;controlled study;disease association;disease severity;DNA sequence;female;gene;gene mutation;hematological parameters;human;major clinical study;male;neurologic disease;oxidative stress;pathophysiology;phenotype;polymerase chain reaction;protein analysis;protein blood level;restriction fragment length polymorphism;serum antioxidant capacity;urine level;Wilson disease/et [Etiology];C reactive protein/ec [Endogenous Compound];copper/ec [Endogenous Compound];DNA/ec [Endogenous Compound];interleukin 10/ec [Endogenous Compound];interleukin 1beta/ec [Endogenous Compound];interleukin 2/ec [Endogenous Compound];interleukin 6/ec [Endogenous Compound];tumor necrosis factor alpha/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Bruha, R.;Vitek, L.;Marecek, Z.;Pospisilova, L.;Nevsimalova, S.;Martasek, P.;Petrtyl, J.;Urbanek, P.;Jiraskova, A.;Malikova, I.;Haluzik, M.;Ferenci, P.",2012,May,http://dx.doi.org/10.1007/s10545-011-9422-5,0,0,
1616,Zinc and human health: An update,"The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson's disease, Alzheimer's disease, and other age-related diseases. © Springer-Verlag 2011.",Apoptosis;Health;Immune response;Metallothioneins;Oxidative stress;Zinc;Zinc biology;aging;atherosclerosis;catalyst;chronic disease;chronic inflammation;clinical feature;cytokine production;degenerative disease;diseases;homeostasis;human;human genome;human health;immunity;malignant neoplastic disease;neurologic disease;nonhuman;nutrition;priority journal;protein motif;review;Wilson disease;zinc binding motif;zinc deficiency;cytokine/ec [Endogenous Compound];ion;protein;trace element,"Chasapis, C. T.;Spiliopoulou, C. A.;Loutsidou, A. C.;Stefanidou, M. E.",2012,April,http://dx.doi.org/10.1007/s00204-011-0775-1,0,0,
1617,Wilson's disease with normal liver function and low copper levels: An uncommon presentation,"LEARNING OBJECTIVE 1: Diagnose Wilson's disease in a patient with normal liver function and low serum copper. LEARNING OBJECTIVE 2: Recognize Wilson's disease in young patients presenting with Parkinsonian features. CASE: A 24 year old previously healthy female was hospitalized with recurrent numbness and headaches accompanied by Parkinsonian symptoms (tremors, slurred speech and drooling with difficulty swallowing). She had a significant family history of psychiatric illnesses in her mother and sister. Physical exam was notable only for mild dysarthria and subjective weakness on the left side. Initial laboratory data including a CBC, basic metabolic panel, liver function tests, thyroid function, ESR, CRP, Lyme PCR, HIV and RPR/VDRL were all negative. She had a normal CSF exam with negative paraneoplastic panel, IgG index, viral studies and cryptococcal antigen. Urinalysis was unremarkable and urine drug screen unrevealing. Autoimmune workup including ANA and rheumatoid factor was negative. A CT scan of the head revealed abnormal, symmetric, diffuse hypo-densities of bilateral basal ganglia. An MRI to further evaluate the soft tissue abnormalities showed increased T2 signal within the right and left lenticular nucleus. A heavy metal screen was ordered. Arsenic, mercury, lead, cadmium and copper levels were all low. Given the high index of suspicion a ceruloplasmin level was ordered which was extremely low at 3.1 mg/dL (normal: 14 - 78 mg/dL). A liver biopsy showed mild chronic active hepatitis grade 2, septal fibrosis stage 3 and retained copper within hepatocytes, confirming a diagnosis of Wilson's disease. An ophthalmologic exam under slit lamp showed clear Kayser-Fleischer (KF) rings. She was started on trientine and zinc, and over subsequent follow up her KF rings disappeared and neurological symptoms showed modest improvement. DISCUSSION: Hepatolenticular degeneration (Wilson's disease) is an autosomal recessive defect in copper export with a prevalence rate of one in 30,000 live births. It is caused by reduced biliary excretion of Copper leading to its buildup in the liver, subsequently progressing to other organs. Diagnosis is based on clinical presentation combined with physical, biochemical and histologic findings. Neurologic disease (present in 35 percent patients) includes Parkinsonian tremor, rigidity and clumsiness of gait, speech problems and drooling. Ten percent patients exhibit psychiatric symptoms varying from subtle personality changes to overt depression, catatonia and paranoia. Serum aminotransferases are usually elevated, but their severity does not correlate with histologic hepatic injury. Total body copper levels are elevated, but serum levels may be low in patients with low ceruloplasmin levels. In the presence of only neurological symptoms with normal liver function and low copper levels, a slit lamp exam to look for KF rings should be considered. If positive, it strongly suggests Wilson's disease. A liver biopsy may be required for further confirmation of the diagnosis.",internal medicine;society;liver function;human;patient;Wilson disease;diagnosis;neurologic disease;slit lamp;mental disease;female;liver biopsy;hypersalivation;tremor;chronic active hepatitis;swallowing;urinalysis;paranoia;speech disorder;thyroid function;soft tissue;prevalence;basal ganglion;liver function test;rigidity;personality disorder;catatonia;serum;liver injury;blood level;slurred speech;family history;fibrosis;liver cell;density;computer assisted tomography;laboratory;headache;follow up;weakness;dysarthria;autosomal recessive inheritance;live birth;biliary excretion;liver;gait;paresthesia;urine;mother;copper blood level;nuclear magnetic resonance imaging;cerebrospinal fluid;Human immunodeficiency virus;copper;ceruloplasmin;antigen;immunoglobulin G;mercury;heavy metal;arsenic;cadmium;rheumatoid factor;zinc;trientine;aminotransferase;alprazolam,"Gulati, G.;Gulati, S.;Nguyen, H. P.",2012,July,,0,0,
1618,"A riddle wrapped in an enigma, but perhaps there is a key!","LEARNING OBJECTIVE 1: Discuss the differential diagnosis of cirrhosis in a young adult LEARNING OBJECTIVE 2: Discuss significance of work-up forWilson's with diagnostic procedures, the importance of a strong clinical suspicion, and of continuity of care and communication among healthcare providers. CASE: A 26-year-old female with a past medical history of cryptogenic cirrhosis, diagnosed at age 22, presents in December 2011 with a 2-week history of abdominal pain and abdominal swelling. With the loss of insurance about 10 months prior, she was unable to maintain proper dosage of lactulose and lasix and became dependent on the many subsequent ER visits for acute care. The pain characteristics were: sharp, squeezing, pressure sensation, located diffusely over the entire abdomen, and has a severity as high as 10/10. She complained of some nausea and vomiting, fever, and episodes of altered mental status. On exam she was afebrile, normotensive, and in no acute distress. She had significant scleral icterus, and had no apparent changes of mental status. Abdomen was firm and distended, tender to palpation with a positive fluid wave and mild splenomegaly. Abnormal labs: hemoglobin 10.7, hematocrit 32.1, negative hepatitis panel, alkaline phosphatase 532, AST 132, total bilirubin 24.8 (direct 13.6; indirect 11.2), MELD score 26 and her Child Pugh score of 10, PTT of 36, PT 29.7, and INR of 1.88. Review of her previous records from 2010 revealed a normal serum ceruloplasmin level, 24 hour copper excretion of 34 and a positive liver biopsy for copper but without any quantification. The antimitochondrial antibody, ANA, and hemochromatosis gene mutation were negative. She had been treated for depression and substance abuse (EtOH), which was the reason she had not qualified for liver transplant. However, upon further questioning we found out that she only recently used alcohol for coping after she lost her insurance. Our work-up yielded a faint Kayser-Fleischer ring, ceruloplasmin level of 20.1, elevated 24 hour copper at 86 and cooper/creatinine ratio of 78. At this point we concluded that she met the diagnostic criteria for Wilson disease and initiated treatment with D-penicillamine. DISCUSSION: Wilson's disease is an autosomal recessive disorder (gene ATP7B) of copper transport with a prevalence of approximately 1/30000. Typical presentation includes neurological and hepatic dysfunction. Diagnosis usually requires a high index of clinical suspicion due to overlapping symptoms with other disorders. Delayed and misdiagnosis is not uncommon like in our case especially where there is a possible substance abuse history and when lack of insurance becomes a limiting factor for proper follow up and care. Therefore the importance of continuity of care and communication between the physicians cannot be over emphasized. Diagnostic criteria include: presence of Kayser-Fleishcer rings on slit-lamp, ceruloplasmin of <0.20 g/l, 24 h urinary free-copper excretion, penicillamine challenge test, liver copper measurement, and the presence of abnormal gene mutation. Mainstays of therapy include penicillamine, trientine, and zinc. For advanced disease, as in our patient, the long-term treatment is liver transplant.",internal medicine;society;human;diagnosis;insurance;patient care;excretion;abdomen;substance abuse;gene mutation;liver graft;interpersonal communication;mental health;liver cirrhosis;Wilson disease;nausea and vomiting;differential diagnosis;liver biopsy;pressure sensation;medical history;hepatitis;liver dysfunction;pain;Child Pugh score;ceruloplasmin blood level;provocation test;liver;abdominal swelling;young adult;abdominal pain;female;emergency care;health care personnel;hematocrit;splenomegaly;liquid;palpation;coping behavior;jaundice;autosomal recessive disorder;gene;prevalence;diseases;diagnostic error;follow up;physician;slit lamp;hemochromatosis;fever;therapy;diagnostic procedure;patient;long term care;international normalized ratio;copper;penicillamine;ceruloplasmin;alkaline phosphatase;bilirubin;trientine;mitochondrion antibody;furosemide;hemoglobin;lactulose;alcohol;zinc;alprazolam,"Sapkota, S. K.;Sutton, G.;Patel, B.;Staton, L.;Panda, M.",2012,July,,0,0,
1619,A case of acute copper toxicity,"LEARNING OBJECTIVE 1: Wilson disease, also known as hepatolenticular degeneration, is due to an autosomal recessive defect in copper transportation. Ceruloplasmin represents circulating copper in the plasma. The hepatic production of apoceruloplasmin, ceruloplasmin without copper, causes the low level of serum ceruloplasmin found in patients with Wilson disease. Furthermore, the inappropriate function of theWilson disease protein, ATP7B, leads to an impairment in biliary copper excretion, which allows copper to accumulate and deposit in the hepatic, neurologic, renal, and ophthalmic systems. Important clinical features of the disease include cirrhosis, acute liver failure, movement disorders, psychosis, and premature osteoporosis. CASE: 25 year old male with a history of panhypopituitarism s/p removal of a suprasellar mass secondary to langerhan's histiocytosis presented with altered mental status, generalized weakness, and lethargy. Of note, he had discontinued use of his DDAVP for several weeks. On admission he was found to have a serum sodium level of 172. He was immediately started on pituitary hormone replacement therapy which included, desmopressin, solucortef, and synthroid. Furthermore, he was found to have new onset elevated liver function tests, ammonia, and INR. Initially, his altered mentation was presumed to be a combination of hypernatremia and hepatic dysfunction. As a result, he received lactulose and rifaximin. His sodium level improved, however, he remained encephalopathic. His acute liver failure was further evaluated by gastroenterology and hepatology. Diagnostic laboratory tests revealed low ceruloplasmin, high serum copper, and an elevated urinary copper level. He subsequently underwent a liver biopsy which demonstrated portal fibrosis and steatosis stage III-IV, and portal and parenchymal infiltrates stage II-IV, both were consistent with Wilson disease. He was started on pencillamine which led to immediate improvement in his mental status. The ATP7B gene was pending on discharge. He will undergo a slit lamp exam on an outpatient basis. He was discharged home with close gastroenterology and hepatology follow up. DISCUSSION: Wilson disease should be considered in any individual between ages 3 and 55 with liver abnormalities of uncertain cause, and must be excluded in any patient with unexplained liver disease accompanied by a rapid neurological deterioration. Diagnosis of Wilson dsease is made by a slit lamp examination to identify Kayser-Fleischer rings, which represent deposition of copper in decemet's membrane of the cornea. Biochemical tests demonstrate elevated liver function tests, low levels of ceruloplasmin, and high levels of serum and urinary copper excretion. Increased hepatic parenchymal copper content provides critical diagnostic information and should be obtained in cases where the diagnosis is not straightforward. Histological abnormalities found on liver biopsy include steatosis, hepatocellular necrosis, fibrosis, and cirrhosis. If the diagnosis remains elusive, molecular genetic studies such as the ATP7B mutation can be obtained. Treatment options include D-penicillamine, a chelator that promotes urinary copper excretion, trientine (also a chelator) which is indicated in patients intolerant of pencillamine, and zinc which interferes with uptake of copper from the gastrointestinal tract.",toxicity;society;internal medicine;Wilson disease;diagnosis;human;excretion;patient;steatosis;slit lamp;liver function test;gastroenterology;liver biopsy;mental health;fibrosis;liver cirrhosis;acute liver failure;osteoporosis;hypernatremia;motor dysfunction;plasma;mutation;liver necrosis;psychosis;clinical feature;thinking;cornea;liver dysfunction;deterioration;liver disease;traffic and transport;hormone substitution;follow up;outpatient;autosomal recessive inheritance;gene;sodium blood level;lethargy;copper blood level;laboratory test;weakness;male;liver;membrane;histiocytosis;serum;hypopituitarism;ceruloplasmin blood level;gastrointestinal tract;international normalized ratio;copper;ceruloplasmin;chelating agent;desmopressin;ammonia;levothyroxine sodium;hydrocortisone sodium succinate;penicillamine;trientine;zinc;protein;hypophysis hormone;sodium;rifaximin;lactulose,"Patel, P.;Andhavarapu, K.;Shah, P.;Menon, N.;Feldman, J.",2012,July,,0,0,
1620,7th Central European Gastroenterology Meeting CEURGEM 2012,"The proceedings contain 63 papers. The special focus in this conference is on Gastroenterology. The topics include: Atherosclerosis and arteriosclerosis in viral liver cirrhosis; pancreatic and peripancreatic mass as a presentation of intra-abdominal tuberculosis; C-reactive protein and gastroduodenal lesions in patients with coronary heart disease; HCC and liver transplantation; gastric cancer associated to helicobacter pylori; non-invasive diagnosis of esophageal varices; minimally invasive surgical treatment of colorectal diseases; prognostic significance of diabetes mellitus in patients with liver cirrhosis; a paradigm of panmetabolic Abnormalities; chronobiology of helicobacter pylori eradication with standard triple therapies; metabolic syndrome in chronic hepatitis C; anatomical basis of the central nervous influences on the symptoms in functional gastrointestinal disorders; benign gastrointestinal stromal tumors; multiple gastric ulcers in children receiving single-dose NSAIDS; immunoglobulin G4 related disease; effect of cuprenil on liver disease in Bulgarian patients with Wilson's disease (WD); diet and irritable bowel syndrome; diminutive and small colonic polyps; comparative evaluation of ultrasonographic and radioisotopic assessment of liver nodules; from chronic inflammation to cancer; comparison of inflammatory response to transgastric and transcolonic NOTES; fatty liver disease (FLD) and various alcohol intake in patients with obesity; pentane and carbon disulphide breath concentrations; screening of chronic diffuse liver diseases among the healthy population in republic of Moldova; epidemiology, diagnosis and therapy in animal cryptosporidiosis; carbohydrate-deficient transferrin (CDT) in chronic liver disease; visceral nociception in irritable bowel syndrome; impact and potential treatment of cirrhotic cardiomyopathy; psychological profile in patients with ulcerative colitis and crohn's disease; gastric emptying in type 2 diabetes mellitus - obese versus non obese patients; contrast enhanced ultrasound in the assessment of focal liver lesions; non-invasive serrological assesment of fibrosis in non-alcoholic fatty liver disease (NAFLD); four year follow-up of patients with IBS; extended resections in liver and billiary tumors; bariatric surgery - a viable option for the treatment of obesity; endoscopic diagnosis and treatment in early gastric cancer; alcohol consumption and C-reactive protein levels in chronic liver disease; assessment of the risk factors in patients with upper digestive bleeding and small intestinal bacterial overgrowth syndrome and irritable bowel syndrome.",gastroenterology;human;patient;liver disease;irritable colon;diagnosis;alcohol consumption;neoplasm;obesity;stomach cancer;surgery;Helicobacter pylori;therapy;chronic liver disease;liver cirrhosis;chronobiology;diabetes mellitus;liver transplantation;colorectal disease;abdominal tuberculosis;stomach ulcer;ischemic heart disease;esophagus varices;digestive system function disorder;arteriosclerosis;hepatitis C;screening;Moldova;gastrointestinal stromal tumor;child;single drug dose;inflammation;chronic inflammation;non invasive measurement;colon polyp;metabolic syndrome X;liver nodule;fatty liver;breathing;atherosclerosis;population;diet;epidemiology;bleeding;cryptosporidiosis;risk factor;nociception;cardiomyopathy;ulcerative colitis;stomach emptying;non insulin dependent diabetes mellitus;ultrasound;liver injury;fibrosis;nonalcoholic fatty liver;follow up;bariatric surgery;liver;bacterial overgrowth;Crohn disease;Wilson disease;C reactive protein;carbon disulfide;carbohydrate deficient transferrin;immunoglobulin;penicillamine;pentane,Anonymous,2012,September,,0,0,
1621,Effect of Cuprenil on liver disease in Bulgarian patients with Wilson's disease (WD),"Cuprenil is the standard treatment of WD but its effect on liver disease progression was never established in Bulgarian adult patients. We evaluated the effect of Cuprenil on liver disease progression in 65 Bulgarian patients with WD treated with Cuprenil in average dose 1025 mg/d and followed-up for a mean period of 11.35 years. Adherence to therapy was observed in 72% of cases. In 70% of them was associated with effective level of urine copper excretion (8.34 +/- 11.2 mumol/24h). At the time of diagnosis liver cirrhosis was present in 36 patients and acute/chronic hepatitis - in 29. Normalized level of the liver enzymes was observed in 58% of patients. Liver cirrhosis developed in 57% of patients with chronic hepatitis, but 73% of patients with decompensated liver cirrhosis maintained Child A. In 86% of patients liver disease did not progress. Oesophageal varices did not develop in 63% of patients with liver cirrhosis. During treatment reduction of Kaiser-Fleischer ring was observed in 26% of patients. All patients maintained non-significant proteinuria (0.39+/-.0.29 g/24h). In conclusion, treatment with Cuprenil is well tolerated and delays the natural course of the disease.",liver disease;patient;human;gastroenterology;liver cirrhosis;disease course;patient compliance;hepatitis;proteinuria;diagnosis;excretion;chronic hepatitis;decompensated liver cirrhosis;child;varicosis;urine;adult;penicillamine;liver enzyme;copper,"Sonia, Dragneva;Petkova, T.;Mateva, L.",2012,September,,0,0,
1622,Fulminant wilson's crisis: Plasmapharesis vs mars,"Wilson's disease (WD) presents with chronic hepatic and neurologic dysfunction. In rare cases, it can present with fulminant liver failure and multiple organ dysfunction. Initial therapy aims to decrease the high levels of serum copper characteristic of Wilson's. Since copper is albumin bound, we evaluated the efficacy of 2 modalities of extra-corporeal copper clearance: Molecular Adsorbant Recirculating System (MARS) and plasmapheresis(PP). A 25-year-old woman with WD on Trientine presented with fulminant WD (hemolytic anemia, liver failure, AKI) due to medication noncompliance for 1 year. Blood Copper (Cu), Haptoglobin, and Ceruloplasmin levels were monitored. Treatments alternated between MARS and PP. MARS sessions consisted of 8 hours of albumin dialysis each followed by CVVHDF. PP sessions replaced 1.2 times the plasma volume with FFP. Copper reduction ratios (CRR) for each modality are shown in the table. The patient was bridged to liver transplantation following a total of 5 sessions (3 MARS and 2 PP). In this case, average CRR for MARS and PP were similar (18.6% vs. 26.9%, p=0.5). Side effects of FFP replacement in pharesis are not seen with MARS. Both MARS and PP can be used to for copper clearance in Wilson's crisis and as a bridge to liver transplant. (Figure presented).",kidney;non profit organization;astronomy;human;copper blood level;plasmapheresis;fulminant hepatic failure;liver failure;therapy;female;hemolytic anemia;liver transplantation;neurologic disease;patient;plasma volume;albumin dialysis;side effect;liver graft;drug therapy;continuous hemodiafiltration;Wilson disease;copper;haptoglobin;albumin;trientine;ceruloplasmin,"Mohan, P.;Geara, A.;Kronfol, R.;Long, J.;Radhakrishnan, J.;Parikh, A.",2012,April,,0,0,
1623,Effect of cuprenil on liver disease in bulgarian patients with Wilson's disease (WD),"Cuprenil is the standard treatment of WD but its effect on liver disease progression was never established in Bulgarian adult patients. We evaluated the effect of Cuprenil on liver disease progression in 65 Bulgarian patients with WD treated with Cuprenil in average dose 1025 mg/d and followed-up for a mean period of 11.35 years. Adherence to therapy was observed in 72% of cases. In 70% of them was associated with effective level of urine copper excretion (8.34 +/- 11.2 mumol/24h). At the time of diagnosis liver cirrhosis was present in 36 patients and acute/chronic hepatitis - in 29. Normalized level of the liver enzymes was observed in 58% of patients. Liver cirrhosis developed in 57% of patients with chronic hepatitis, but 73% of patients with decompensated liver cirrhosis maintained Child A. In 86% of patients liver disease did not progress. Oesophageal varices did not develop in 63% of patients with liver cirrhosis. During treatment reduction of Kaiser-Fleischer ring was observed in 26% of patients. All patients maintained non-significant proteinuria (0.39+/-.0.29 g/24h). In conclusion, treatment with Cuprenil is well tolerated and delays the natural course of the disease.",patient;liver disease;human;gastroenterology;Wilson disease;liver cirrhosis;disease course;chronic hepatitis;urine;hepatitis;therapy;adult;varicosis;diagnosis;child;decompensated liver cirrhosis;proteinuria;excretion;penicillamine;copper;liver enzyme,"Dragneva, S.;Petkova, T.;Mateva, L.",2012,,,0,0,
1624,Wilson disease: Abnormal methionine metabolism and the role of inflammation and steatosis in early stages of liver disease,"Purpose of Study: Wilson disease (WD) is a rare autosomal recessive disorder of copper transport featuring hepatic copper accumulation and development of hepatic steatosis. Copper has been shown to inhibit the enzyme S-adenosylhomocysteine hydrolase (SAHH), central in methionine metabolism and in regulating S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) levels. The SAM/SAH ratio is an indicator of methylation capacity and regulates gene expression. This study examines the effects of copper induced SAHH inhibition and treatment with copper chelator penicillamine (PCA) in the pathogenesis of inflammation and steatosis in an animal model of WD in order to establish a link between methionine metabolism and gene expression regulation. Methods Used: Livers and blood were collected from 7 toxic milk (tx-j) and 7 C3H control mice in each age group at 12 and 24 weeks, and 7 PCA treated tx-j mice at 24 weeks. We measured methionine metabolism metabolites SAM and SAH (HPLC) and SAHH activity. Lipid metabolism genes glucose- related protein 78 (GRP78), sterol regulatory element binding protein 1c (SREBP 1c), carnitine palmitoyltransferase 1alpha (CPT-1alpha), peroxisome proliferator activated receptor alpha (PPARalpha), and proinflammatory tumor necrosis factor alpha (TNFalpha) were measured via Real Time-PCR. Summary of Results: Hepatic copper levels in tx-j mice were 35-40 times greater than controls (p<0.0001) while PCA tx-j mice accumulated half as much copper as untreated tx-j mice (p<0.0001). At 24 weeks, SAHH activity was reduced in tx-j mice (p=0.01) but re-established similar to controls in PCA tx-j mice. The SAM/SAH ratio was lower in PCA and untreated tx-j mice (p<0.05). GRP78, SREBP 1c, CPT-1alpha and PPARalpha expressions were reduced in untreated tx-j mice at both ages and further reduced in PCA tx-j mice. TNFalpha expression was higher in untreated tx-j mice but reduced in PCA tx-j mice. Conclusions: Copper accumulation is associated with SAHH activity inhibition in tx-j mice that was restored in PCA tx-j mice. The SAM/SAH ratio was reduced in PCA and untreated tx-j mice with changes in the inflammation and steatosis gene expression. These findings indicate that copper induced abnormal methionine metabolism and subsequent inflammation and zsteatosis play an important role in the pathogenesis of early liver disease in WD.",Wilson disease;metabolism;inflammation;steatosis;liver disease;medical research;mouse;pathogenesis;gene expression;methylation;groups by age;milk;liver;gene expression regulation;animal model;blood;metabolite;lipid metabolism;gene;autosomal recessive disorder;real time polymerase chain reaction;fatty liver;methionine;copper;sterol regulatory element binding protein 1c;peroxisome proliferator activated receptor;s adenosylmethionine;glucose;protein;carnitine palmitoyltransferase I;s adenosylhomocysteine;penicillamine;adenosylhomocysteinase;chelating agent;enzyme;tumor necrosis factor;sterol regulatory element binding protein 1,"Dolatshahi, M.;Shibata, N.;Liu, S.;Halsted, C.;Medici, V.",2012,January,http://dx.doi.org/10.231/JIM.0b013e318240c940,0,0,
1625,Usefulness of dynamic hepatobiliary scintigraphy in Wilson's disease,"Wilson disease (WD) is an autosomal recessive disorder of copper transport due to defective hepatocyte-biliary copper excretion, resulting in pathological accumulation of copper in many organs and tissues, primarily in the liver and brain. Clinical manifestations related to copper accumulation in the liver include hepatic disease ranging from mild hepatitis to acute liver failure or cirrhosis. The aim of this study was to investigate the potential role of dynamic hepatobiliary scintigraphy (DHBS) in the evaluation of liver dysfunction in patient with Wilson's disease. Material and Methods: DHBS with 99mTc Mebrofenin were performed in 39 consecutive WD patients treated with zinc and/or penicillamine (19 males e 20 females; mean age 39+/-4 years) with clinical evidence of hepatic disease. All patients underwent standard biochemical liver function tests including ALT, AST,GGT,AP, TOT BIL, ALB, serum copper and caeruloplasmin, and 24-h urinary copper excretion. Liver biopsies were performed in all WD patients. Liver tissue was examined for routine liver histology (grading and staging of fibrosis) and hepatic copper content. DHBS was performed after 110 MBq99mTc Mebrofenin i.v. injection by time/frame acquisition 30 sec for 60 min. Time-activity curves were recorded from regions of interest placed over hepatic parenchyma (H) and main intra-hepatic biliary ducts (B). Quantitative analysis of the curves was performed using deconvolutional analysis and non-linear regression measuring the time to maximum peak counts intra-parenchimal (HTmax) and intra-ductal (B Tmax) and the time to T1/2 excretion (HT1/2 ;BT1/2 ) . Results: All patients had low serum caeruplasmin and copper levels, respectively (3.05+/-0.2mg/dl and 57+/-18mug/dl) and high 24h urinary copper excretion (201+/-42mug/24h). According to Metavir fibrosis staging 16 patients (41%) was classified as F1, 7 as F2 (18%), 10 as F3 (25%) and remaining 6 as F4 (16%) The analysis of DHBS quantitative data showed in almost patients slow hepatic uptake (>HTmax) and hepatobiliary excretion (>HT1/2). A positive correlation was observed between histological findings and Htmax (p=0,001), HT1/2 (p=0.006) and BTmax (p=0.02) values. Furthermore, in multivariate analysis, significative correlation was found between HTmax, HT1/2 BT1/2 and high fibrosis degree (F4) vs the other grading of fibrosis. No correlation was found between biochemical liver function tests, but bilirubin; (p < 0.01) and DHBS parameters. Conclusion: This study showed the clinical utility of the DHBS as noninvasive diagnostic modality to evaluate the liver fibrosis degree allowing to reduce the number of liver biopsy in the long-term follow-up in Wilson disease patients.",nuclear medicine;hepatobiliary scintiscanning;Wilson disease;human;patient;excretion;fibrosis;liver;liver function test;liver biopsy;staging;liver disease;liver dysfunction;liver histology;acute liver failure;tissues;liver cirrhosis;parenchyma;hepatitis;copper blood level;liver cell;male;follow up;liver fibrosis;parameters;injection;bile duct;quantitative analysis;linear regression analysis;multivariate analysis;female;serum;diagnosis;hospital patient;brain;autosomal recessive disorder;copper;mebrofenin;ceruloplasmin;penicillamine;zinc;bilirubin;technetium 99m,"Serra, A.;Sorbello, O.;Loi, G.;Mighela, M.;Faa, G.;Demelia, L.;Piga, M.",2012,October,http://dx.doi.org/10.1007/s00259-012-222-x,0,0,
1626,A precious metal: Copper deficiency presenting as myeloneuropathy,"Background: Copper deficiency is a rare cause of haematological and neurological disease. We describe a case of copper deficiency mimicking subacute combined degeneration of the cord. Methods: A 65 year old woman presented with leg weakness, poor balance and paraesthaesia in her hands and legs. She was known to have coeliac disease and B12 and folate deficiency, with erratic compliance with B12 injections. There were no features of inflammatory joint or muscle disease, or of an underlying autoimmune connective tissue disorder. Neurological examination revealed normal tone and power with brisk reflexes. She had a sensory level at midthigh, with proprioception reduced to the ankles and vibration sense absent up to the hips. Sensory ataxia and a positive Romberg's test were demonstrated. Her clinical picture suggested combined myeloneuropathy. In view of her medical history, actual or functional B12 deficiency was suspected. MRI spine and nerve conduction studies showed no specific changes. Blood tests, including B12, folate, inflammatory markers and autoimmune profile were normal. However, copper studies were abnormal, with serum copper level low at 2.3 [normal range 11-20], caeruloplasmin 0.1[NR 0.2-0.6], and zinc 6.1 [NR 11-24]. She was diagnosed with copper deficiency. With oral copper supplementation, her symptoms have improved. Results: Copper deficiency is recognized as a cause of myelopathy in humans and other animals, particularly ruminants. Copper chelators are used in animal models to model demyelination and neurodegenerative phenomena. In humans, it has been seen following gastric bypass surgery or after excessive use of zinc-containing denture adhesives, although many cases are idiopathic. The disease may mimic subacute combined degeneration of the cord, optic neuropathy, or myelodysplasia with refractory anaemia and other cytopenias. Copper deficiency myelopathy is commoner amongst women, peaking in the 5th and 6th decades. This picture is not seen in Wilson's disease, but in cases of clinical doubt, copper deficiency can distinguished by demonstrating low levels of urinary copper. Spinal MRI may show increased T2 signal in the posterior cervical and thoracic cord. It is unclear how copper deficiency causes neurodegeneration, or why it appears similar to other deficiency related neurodegenerative conditions. Dysfunction of cytochrome oxidase, and of the methylation process involved in the synthesis of the myelin protein, may explain both the pathogenesis and the similarity between the phenotypes. Conclusions: Copper deficiency is a rare cause of neurodegenerative symptoms that may mimic other conditions. A combination of myelopathy and cytopenia is particularly suspicious. Clinicians should be alert to this possibility, especially in patients with risk factors such as malabsorption, bariatric surgery or megadoses of zinc. After treatment, cytopenias usually resolve, but neurological recovery is often incomplete.",rheumatology;society;human;health practitioner;copper deficiency;spinal cord disease;subacute combined degeneration;female;leg;celiac disease;hip;neurologic disease;weakness;nuclear magnetic resonance imaging;neurologic examination;proprioception;ankle;vibration sense;denture;medical history;spine;copper blood level;connective tissue disease;injection;patient;malabsorption;muscle disease;bovids;animal model;model;demyelination;stomach bypass;bypass surgery;blood;optic nerve disease;myelodysplastic syndrome;methylation;folic acid deficiency;nerve conduction;synthesis;pathogenesis;phenotype;cytopenia;nerve degeneration;risk factor;refractory anemia;bariatric surgery;supplementation;reflex;Wilson disease;metal;copper;cyanocobalamin;zinc;ceruloplasmin;marker;folic acid;chelating agent;adhesive agent;cytochrome c oxidase;myelin protein,"Hayes, F.;Coward, L.;Borg, F.",2012,May,http://dx.doi.org/10.1093/rheumatology/kes108,0,0,
1627,"Clinical, biochemical and radiological profile of Wilson's disease and effect of treatment","Objectives: To study clinical, biochemical and radiological profile of Wilson's disease(WD)and effect of treatment. Methods: This study was carried on 31 patients who were subjected to a detailed clinical history, physical and neurological examination. Slit lamp examination of cornea for Kayser-Fleischer (KF) ring, biochemical studies (including serum ceruloplasmin, copper and urinary copper) and neuroimaging was done in all patients. Results: The mean age of onset was 12.41 years and the mean delay in diagnosis was 16.96 months. 24 (77.4 %) patients were juveniles (age below 18 years) and 7 (22.6 %) were adults (age more than 18 years). Dystonia was the commonest initial neurologic feature (64.5 %) followed by dysarthria (41.9 %), drooling of saliva (38.7 %) and parkinsonism (38.7 %).Among the main neurologic features, the dystonic group (83.9 %) predominated followed by the parkinsonian group (64.5 %), cerebellar group (22.6 %) and the choreoathetoid group (9.7 %).While parkinsonism predominated in the juvenile group, cerebellar features predominated in the adults. Psychiatric complaints (41.9 %), seizures (19.4 %) and headache (22.5 %) were also observed. Bilateral KF ring was seen in all patients. Non-neuropsychiatric features(bleeding, hepatosplenomegaly and joint pains) were seen predominantly in juveniles. Serum ceruloplasmin was low (<20 mg/dl) in 93.54 % patients, 24 h urinary copper (>100 microgram/ day) was increased in all patients and serum copper was low (<75 microgram/dl) in 64.5 % patients. MRI brain was done in 27 patients with basal ganglia signal changes being the commonest finding (85.2 %). 4 patients had CT scan brain done with basal ganglia hypodensity being the commonest finding (75 %).All patients were treated with zinc and penicillamine. 23 (74.2 %) patients took regular treatment with neurological worsening occurring in 16 (51.6 %) patients. 13 (41.9 %) patients improved completely; 12 (38.7 %) patients showed incomplete improvement with sequelae; 4 (12.9 %) patients remained status quo and were lost in follow up and 2(6.45 %) patients deteriorated and died. Conclusions: This series of WD from Eastern India highlights that the disease is not that rare in India and has varied clinical presentations. Dystonia and parkinsonian features predominated in juvenile patients, while cerebellar features predominated in the adult group. Screening of all asymptomatic siblings for WD must be carried out. Early diagnosis and proper treatment can prevent devastating consequences.",society;Wilson disease;human;patient;juvenile;adult;ceruloplasmin blood level;parkinsonism;basal ganglion;India;dystonia;arthralgia;diagnosis;neurologic examination;onset age;headache;brain;seizure;neuroimaging;screening;bleeding;hepatosplenomegaly;copper blood level;cornea;slit lamp;saliva;brain scintiscanning;hypersalivation;computer assisted tomography;follow up;sibling;early diagnosis;dysarthria;nuclear magnetic resonance imaging;copper;penicillamine;zinc,"Kumar, N.;Joshi, D.",2012,June,http://dx.doi.org/10.1007/s00415-012-6524-4,0,1,
1628,Therapeutic efficacy of trientine dihydrochloride encapsulated alginate/chitosan nanoparticles in rat model of copper toxicity with neurobehavioral impairments,"Animal models of Wilson's disease (WD) viz. Long evans cinnamon rats, rarely exhibit neurological symptoms impeding the development of novel therapeutic approaches like nanoparticle based drug delivery across BBB to treat neurological manifestations in WD patients. The aim of this study was to (1) examine the effects of intraperitoneally injected copper lactate daily for 90 days especially on copper levels in brain tissues, expression of metallothionein-I (MT-I) & Atp7b gene in liver and MT-III & acetylcholine esterase (AChE) gene in brain (by reverse transcription-PCR) and, neurobehavioral functions (by Morris water maze) of male Wistar rats. (2) evaluation of orally administered copper chelator Trientine dihydrochloride encapsulated alginate/chitosan nanoparticles for 90 days in copper intoxicated Wistar rats. Copper administered animals showed significantly increased ceruloplasmin, serum & urine copper levels, decreased serum AChE activity, increased expression of hepatic MT-I gene with impaired neuromuscular coordination and spatial memory. Autopsy studies of copper intoxicated rats revealed a significant increase in the liver and brain copper content (99.1% and 73% increase respectively), decreased liver zinc (40% decrease) & interestingly, increased brain zinc content (77.1% increase) compared to controls rats. Copper deposition in the liver and brain tissues and copper associated proteins in liver tissues of test rats was substantiated by rhodanine and orcein stains respectively. Nanoparticles based therapy resulted in significant reduction of hepatic copper content, serum ceruloplasmin level & increase in serum AChE activity. In conclusion, chronic copper toxicity may lead to increased copper content in liver & brain, increased hepatic MT-I gene expression, high serum Cu, ceruloplasmin levels, urine copper and, neurobehavioral impairments may be by interfering in acetylcholine modulated neurotransmission; however, trientine dihydrochloride encapsulated nanoparticles may reverse impairments caused by chronic copper intoxication to a significant extent in Wistar rats.",rat;animal model;toxicity;Asian;therapy;liver;serum;brain;gene;Wistar rat;urine;brain tissue;patient;drug delivery system;intoxication;Long Evans cinnamon rat;male;maze test;reverse transcription polymerase chain reaction;ceruloplasmin blood level;neurologic disease;autopsy;spatial memory;stain;human;gene expression;neurotransmission;Wilson disease;blood brain barrier;trientine;nanoparticle;copper;ceruloplasmin;zinc;acetylcholine;rhodanine;acetylcholinesterase;water;protein;metallothionein I;chelating agent,"Pal, A.;Prasad, R.;Thapa, B. R.;Vasishta, R. K.;Attri, S. V.",2012,December,http://dx.doi.org/10.1111/jgh.12006,0,0,
1629,Rat model of copper toxicity with neurobehavioral impairments,"Animal models of Wilson's disease (WD) viz. Long evans cinnamon rats, rarely exhibit neurological symptoms impeding the development of novel therapeutic approaches to treat neurological manifestations in WD patients. The aim of this study was to investigate the effects of intra-peritoneally injected copper lactate (0.15 mg Cu/100 g. B.W.) daily for 90 days especially on copper and zinc levels in liver, kidney & brain (mainly hippocampus region) tissues; expression of hepatic metallothionein-I (MT-I) & Atp7b gene, and MT-III & acetylcholine esterase (AChE) gene in brain, biochemical parameters, and neurobehavioral functions (by morris water maze test) of male Wistar rats. Copper administered animals showed significantly increased serum ceruloplasmin levels, serum & urine copper levels, decreased serum AChE activity, increased expression of hepatic MT-I gene with impaired neuromuscular coordination and spatial memory compared to control rats. Notwithstanding there were no changes in the expression levels of hepatic Atp7b gene and MT-III and AChE gene in brain tissues of Cu intoxicated rats. Cu intoxicated rats showed a signifi- cant increase in Cu content of the liver, hippocampus region of brain and kidney tissues (99.1, 73 and 74.9% increase respectively), whereas there was 40% reduction of hepatic Zn content & interestingly, 77.1% increase in the Zn content of the hippocampus region of brain tissues compared to controls rats. Histopathological studies demonstrated copper deposition in the liver and brain (with swollen astrocytes) tissues, and copper associated proteins in liver tissues of Cu intoxicated rats substantiated by rhodanine and orcein stains respectively. In conclusion, present study show the first evidence in vivo that chronic Cu toxicity causes neurobehavioral impairments, decreased serum AChE activity, Cu deposition in brain with swollen astrocytes, augmented levels of Cu and zinc in hippocampus of male Wistar rats.",animal model;toxicity;Asian;rat;gene;brain;liver;hippocampus;serum;Wistar rat;male;brain tissue;astrocyte;tissues;urine;kidney;neurologic disease;maze test;human;ceruloplasmin blood level;stain;patient;parameters;Long Evans cinnamon rat;histopathology;kidney parenchyma;spatial memory;Wilson disease;copper;zinc;water;protein;acetylcholinesterase;metallothionein I;rhodanine,"Pal, A.;Prasad, R.;Vasishta, R. K.;Attri, S. V.;Thapa, B. R.",2012,December,http://dx.doi.org/10.1111/jgh.12006,0,0,
1630,Presentation of Wilson's disease in Pakistan: A tertiary care hospital experience in Karachi Pakistan,"Background: Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism, with an average worldwide prevalence of approximately 1 in 30,000 people. Data regarding WD from Pakistan is not available hence we aim to determine the pattern of WD in Pakistan population and wanted to compare with international literature. Methods: Cross sectional study from 1985-2010, conducted at Aga Khan University Hospital Karachi. Results: 47 patients were seen, 32 (68.1%) were male with mean age (SD) was 26.6 (9.97) years. Most common mode of presentation was hepatic; 22 (46.8%) then neurological; 17 (36.2%) and rest were presented with psychiatric symptoms 8 (17%). Patients with psychiatric symptoms had earlier onset of WD at the mean age of 18.8 +/- 3.3 years. Mean ceruloplasmin levels were 0.17 (0.13) and was reduced (<0.25 g/dl) in 39 (86.6%). Serum (Cu) was reduced in 32 (68.1%). 24 hr urinary Cu was raised in only 22 (47.6%). Slit Lamp examination for Kayser-Fleischer (KF) rings was done on 15 (31.9%) patients and only 9 (60%) patients were found to have KF rings. Out of these 9 patients with KF ring positive, 8 (88.8%) had neurologic disease. Mean (AST)/(ALT) ratio was 1.92 and median ALP/T. Bilirubin ratio was 79.30 (IQR 35.05; 166.50). Thirty one (65.4%) patients were given combination of D-Penicillamine and Zinc (Zn), 11 (23.1%) patients were given only D-Penicillamine and only 5 (11.5%) were on Zn alone. Only one patient who presented with decompensated liver disease underwent liver transplant. Conclusion: Patients with WD present slightly later in adulthood in our population and hepatic presentation is the most common. The disease presentation and biochemical parameters in Pakistan are not different from the rest of the world. WD should be suspected in patients who have unexplained abnormal liver function tests and had family history is positive for liver disease.",Pakistan;hospital;Asian;tertiary health care;Wilson disease;human;patient;population;mental disease;cross-sectional study;prevalence;neurologic disease;serum;slit lamp;liver disease;parameters;copper metabolism;adulthood;liver graft;male;decompensated liver cirrhosis;university hospital;liver function test;family history;autosomal recessive disorder;zinc;penicillamine;bilirubin;ceruloplasmin,"Parkash, O.;Ayub, A.;Jafri, W.;Alishah, H.;Hamid, S.",2012,December,http://dx.doi.org/10.1111/jgh.12006,0,1,
1631,Common metabolic liver diseases in children: Wilson's disease,"WiIson's disense (WD), an autosomal recessive disorder of copper metabolism, was firstly described by a neurologist, Dr. Samuel Alexander Kinnier Wilson, in 1912. The estimated worldwide prevalence is 1 to 30,000-40,000 live births. Although the common age of onset is between childhood and young adulthood period, there were case reports of extreme WD cases in a 2-year-old girl and 72-year-old woman with hepatomegaly and neurological disability, respectively. Clinical manifestations are signifi cantly variable, including liver diseases, neurologic disorders, and psychiatric symptoms. These symptoms are usually indistrinctive from other common diseases. Therefore, a high index of suspicion is required to guide physicians to properly start investigating and provide a prompt treatment in such the treatable fatally-outcome-related disease. Mutations in ATP7B gene lead to reduction in hepatic excretion of copper, associated with oxidative stress-induced cell injury in various organs. Numerous mutations have been discovered since 1993. Despite the definite diagnosis made from the genetic analysis, its routine application has not been used generally due to the gene length and numerous mutations. WD is, thus, practically diagnosed by typical clinical setting with/or without Kaser- Fleischer ring and some supporting laboratories including low serum ceruloplasmin (<0.2 g/l), high 24-hour urinary copper (>100 mug/day), and high hepatic copper content (>250 mug/g dry weight). Liver transplantation is the ultimate choice of treatment in the patients presenting with fulminant hepatic failure. However, early diagnosis and treatment can prevent and reverse fatal outcome. Copper chelating agents, pencillamine and/or trientine, has been used with some limitations regarding their side effects. There is evidence that penicillamine can deteriorate neurologic function; in which tetrathiomolybdate and zinc may be good alternatives. The effi- cacy and safety of zinc therapy have been proven not only in symptomatic patients, but in presymptomatic and patients with pregnancy.",human;liver disease;Asian;child;Wilson disease;female;patient;mutation;gene;neurologist;live birth;hepatomegaly;onset age;prevalence;copper metabolism;girl;diagnosis;case report;dry weight;liver transplantation;disability;neurologic disease;mental disease;diseases;physician;oxidative stress;autosomal recessive disorder;adulthood;cell damage;pregnancy;genetic analysis;laboratory;ceruloplasmin blood level;excretion;childhood;fulminant hepatic failure;early diagnosis;fatality;side effect;safety;therapy;copper;zinc;tetrathiomolybdic acid;chelating agent;trientine;penicillamine,"Ukarapol, N.",2012,December,http://dx.doi.org/10.1111/jgh.12005,0,0,
1632,Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease,"BACKGROUND: Wilson disease(WD) requires life-long medical therapy. Patients that frequently miss dosages of their medications can develop liver failure, neurological or psychiatric disease. Current therapy for WD is with chelating agents or zinc salts given in divided dosages. AIM: To prospectively determine if trientine given once daily is effective maintenance therapy for WD and improves patient adherence to treatment. Methods: The study group included seven male and 1 female patient ages 22-71 yrs with stable disease. Patients were treated for their WD from 4 to 50 yrs. Presentations of WD included asymptomatic detection by family screening (n=1), incidental Kayser-Fleischer rings (n=1), neuropsychiatric then liver disease (n=1) and primary liver disease (n=5). Prior treatments were zinc acetate (n=2),d-penicillamine (n=1) and trientine (n=5). After monitoring for 3 months on their prior medications,patients were treated with a single daily weight based dose of trientine (15 mg/kg). Close monitoring on treatment included clinical exam, blood counts and biochemical testing. RESULTS: After 12 months of treatment all patients were clinically well and their clinical exams were stable throughout the study period. There were no treatment stoppages for elevated transaminases or side effects. There was no evidence of significant fluctuations in blood counts. Urinary copper excretion increased in patients who were on zinc, but was relatively unchanged for patients previously on d-Penicillamine or trientine. Mean 24-hour urine copper and zinc excretion at end of treatment were 313.4 +/- 191.7 and 2214 +/- 1346 micrograms respectively. Results of patient questionnaires at the end of the study reported by all the individuals in the study group indicated that a major advantage of trientine given in a once daily dosage was the convenience of not having to time dosages to the recommended one hour before or two hours after meals throughout the day. This regimen was reported by these patients to have improved their adherence to treatment, two of whom were missing more than 5 doses a week before the study. CONCLUSIONS: Once daily trientine is an effective maintenance therapy for WD and improves adherence to lifelong medical therapy. Longer-term follow up will establish the safety, and treatment efficacy of this once daily treatment regimen for WD.",Wilson disease;liver disease;liver;pilot study;human;patient;therapy;blood cell count;monitoring;maintenance therapy;drug therapy;safety;follow up;screening;zinc urine level;male;excretion;patient compliance;female;side effect;hypertransaminasemia;weight;urine;questionnaire;mental disease;liver failure;trientine;penicillamine;copper;zinc acetate;zinc;zinc derivative;chelating agent,"Ala, A.;Aliu, E.;Schilsky, M. L.",2012,October,http://dx.doi.org/10.1002/hep.26040,0,0,107
1633,Long-term outcome of a large patient cohort with Wilson disease in Austria,"Wilson disease (WD) is a genetic disorder due to impaired hepatic copper excretion resulting in copper accumulation in the liver and many other organs. Limited data are available on the long-term outcome of patients with WD. In Austria 223 patients (2.77/100000 inhabitants) with WD were diagnosed 1961-2011.One patient moved abroad, and could not be reachen Methods: The 165 patients alive or their treating physicians were contacted to obtain information on their current status in 2011. No data were obtained in 56 patients. In these patients information on their survival status was obtained from the Austrian Statistics Office (Statistik Austria, Vienna). The median observation period was period 14.4 years (range: 0.5- 49), total: 3028 patient years. Results: The follow-up study included 222 patients (115 female/107 male; presentation: hepatic: 133; neurologic: 57, asymptomatic 22; age at symptomatic onset 22.3+/-12.3 [range: 2-61] years). 16 patients (7.2%) died during the observation period (in 12 patients death was related to WD - 7 hepatic decompensation, 3 after liver transplantation (LTX), 1 accident to neurologic impairment, 1 suicide). 28 (12.6%) patients required LTX (8 fulminant WD, 19 end stage liver disease, 1 neurologic worsening). LTX was performed within a few months following diagnosis; only 3 patients underwent LTX several years after diagnosis (inspite of good treatment compliance). Overall survival was 92% after 20 years, slightly worse than that of the age adjusted Austrian population (97%). Survival of patients living 10 years after diagnosis was not different form the healthy cohort. 96 vs. 99%). 41 (18.4%) fully recovered, and 38 (17.1 %) patients improved after initiation of therapy (d-pecillamine or trientine). Most of the remaining patients were stable, only 7 deteriorated (3.2%) despite of medical therapy. No clinical follow up was obtained in 45 patients. Conclusion: WD is associated with serious, often fatal liver disease. 12.6% require liver transplantation. If patients survive for 10 years after initiation of treatment (medical or transplantation) their long-term prognosis in terms of survival and of clinical condition is excellent. Thus early diagnosis and initiation of treatment is mandatory to further improve survival and decrease the need for transplantation.",human;Wilson disease;Austria;liver disease;liver;patient;survival;diagnosis;liver transplantation;therapy;follow up;transplantation;suicide;accident;decompensated liver cirrhosis;early diagnosis;death;prognosis;male;excretion;population;overall survival;statistics;patient compliance;end stage liver disease;physician;genetic disorder;copper;trientine,"Beinhardt, S.;Leiss, W.;Graziadei, I.;Stauber, R. E.;Maieron, A.;Datz, C.;Vogel, W.;Ferenci, P.",2012,October,http://dx.doi.org/10.1002/hep.26040,0,1,
1634,Wilson disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease,"Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH), which is a potent inhibitor of methylation reactions. Methods: We studied transcript levels of Sahh, S-adenosylmethionine (SAM), SAH, transcripts of DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b), and hepatic global DNA methylation in the toxic milk mouse (tx-j), an animal model of WD and in control C3H mice. Tx-j mice (n=6-7/treatment group, males) received oral penicillamine in deionized water at 100 mg/Kg b.w./day from 12 to 24 weeks of age and, in separate experiments, both tx-j and C3H mice received the methyl donor betaine supplemented at 1.5% in the drinking water from 20 to 24 weeks of age to modulate inflammatory and methylation status, respectively. Hepatic global DNA methylation was assessed by dot blot analyses and immunostaining was used to detect and quantify 5-methylcytosine in hepatocytes nuclei. Results: In the untreated state, hepatic Sahh transcript and protein levels were reduced in 24 wk old tx-j mice (p<0.05) with consequent increase of liver SAH levels (56.8+/-13 vs 33.4+/-8.5 nmol/g; p<0.05). Hepatic Cu accumulation in tx-j mice (259+/-104 vs 7.2+/-1.5 ug/g. d.w., p<0.001) was associated with inflammation, as indicated by liver histology, elevated serum ALT (238+/-49 vs 36+/-14 U/L, p<0.001), and elevated liver tumor necrosis factor alpha (Tnf- alpha) transcript levels (2.9+/-1.2 vs -0.56+/-1.4 fold changes, p<0.05). Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation (about 10% reduction compared to C3H mice). Cu chelation treatment of tx-j mice with penicillamine reduced Tnf-alpha and ALT levels, betaine treatment increased SAM, up-regulated Dnmt3b levels, and both treatments raised DNA methylation in tx-j to control levels. Immunostaining for 5-methylcytosine showed diffuse and less intense nuclear pattern of staining in hepatocytes nuclei from tx-j mice (p<0.01). Conclusion: reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by improving inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD.",liver disease;Wilson disease;DNA methylation;metabolism;inflammation;liver;mouse;methylation;liver cell;immunohistochemistry;chelation;donor;liver injury;male;animal model;gene expression;model;milk;liver tumor;gene;serum;liver histology;staining;methionine;dna;penicillamine;5 methylcytosine;betaine;s adenosylmethionine;s adenosylhomocysteine;drinking water;copper;water;adenosylhomocysteinase;methyl group;tumor necrosis factor alpha;methyltransferase;protein,"Medici, V.;Kharbanda, K. K.;Woods, R.;LaSalle, J. M.;Torok, N.;Halsted, C. H.",2012,October,http://dx.doi.org/10.1002/hep.26040,0,0,
1635,Controversies in diagnosing and treating Wilson disease in children - Results of an international survey,"Introduction: In rare pediatric metabolic diseases, insufficient evidence guiding the management may lead to variations in care. The aim of this study is to determine consensus and variation in how pediatric hepatologists (PH) diagnose and treat Wilson disease (WD) patients. Methods: PH, either members of AASLD Pediatric Liver Special Interest Group or ESPGHAN, were invited to participate in this web-based, international survey. Results: Participation was 43% (108 respondents, 253 invitations).The majority (64%) see 1-10 WD patients regularly and 30% see >=11. Publications by Roberts and Schilsky (Hepatology 2008) and Ferenci et al. (Liver Int. 2003) were preferentially used as guidelines (65% and 21%, respectively). Interpretation and use of laboratory data were variable. Whereas for 90%, basal 24-hr urine copper excretion (UCE) >0.6mumol (40mug)/24h indicated a need for further investigations, definition of normal liver copper content (LCC) varied (25% interpreted 50mug/g and 56% 250mug/g as pathological). Genetic testing is performed in all patients by 48% and not at all in 13% in suspected WD cases, although tests are commercially available. Regardless of disease severity, in patients from previously unaffected families, serum ceruloplasmin (CER), UCE and LCC were the preferred diagnostic tools. However, once genotype of an index patient was known, DNA analysis was 1 of 3 methods of preference (80%). Although not preferred, the penicillamine (PEN) challenge was similarly applied in asymptomatic and symptomatic patients (20% and 26%). Screening a child of an individual with WD, depending on CER, UCE and genetic testing, was chosen by 76%. Use of a low-copper diet was judged diversely: 45% recommend indefinite, 33% temporary, and 12% do not advise any diet. The drug of choice for primary therapy varied significantly. Zinc monotherapy was preferred in a 4-year old affected sibling of a WD patient with elevated aminotransferases (43%). In older patients, PEN and trientine, were generally equally preferred but PEN was rejected by 51% of North American vs. 7% of respondents from other countries. Concepts on managing a WD patient with acute liver failure (ALF) varied. Chelators were chosen by 52% and transplantation by 15% as primary treatment. Monitoring by disease severity score while applying medical therapy is the accepted approach by the majority. However, 23% reported to monitor only, without chosing chelation therapy or an alternative. Conclusions: The approach to diagnosing and treating WD in children by PH is distinctly variable. The reasons for these differences in clinical practice are not entirely clear but likely include regional variations.",Wilson disease;child;human;liver disease;liver;patient;pH;diet;therapy;genetic screening;disease severity;DNA determination;diagnosis;chelation therapy;ceruloplasmin blood level;monitoring;transplantation;consensus;metabolic disorder;acute liver failure;sibling;monotherapy;excretion;screening;urine;laboratory;clinical practice;genotype;copper;penicillamine;chelating agent;trientine;aminotransferase;zinc;dna,"Piersma, F. E.;Tanner, S.;Socha, P.;Roberts, E. A.;Shneider, B. L.;Sturm, E.",2012,October,http://dx.doi.org/10.1002/hep.26040,0,0,
1636,Wilson's disease in Oman: A study of neurological manifestations and diagnostic delay from a University Teaching Hospital,"Background: There are no comprehensive clinical accounts of Wilson's disease [WD, an autosomal recessive disorder (OMIM 277900) of copper transport] in Oman, where there is a high frequency of consanguineous marriages. Objective: To study the neurological, demographic and imaging profiles of WD cases in Oman and to ascertain the time delay in diagnosis. Design and methods: The clinical features and MRI findings of WD cases (who attended the Neurological service of Sultan Qaboos University Hospital, Oman) were retrieved from the electronic patient records. Patients were also contacted by telephone to ascertain the family history and the time-delay in diagnosis. Results: We studied a total of 22 cases (13 males and 9 females) from 4 different Omani families. 9 subjects from these families had neurological manifestations, with the mean age at symptom onset of 18 years (range: 12-24). These subjects demonstrated varying combinations and severity of dystonia, tremor, dysarthria, dysphagia, pyramidal signs and affective disorder. MRI showed basal ganglionic signal changes in those with persisting neurological deficits (n=4). Median time-delay in the diagnosis was 3 months (range: 0-16 months). Maintenance treatment included penicillamine (n= 3), trientine (n= 4) and zinc sulphate (n= 2). A recent genetic study of one of the 4 families revealed a novel homozygous splice site mutation (C.2866-2A>G) upstream of exon 13 in the copper transporter gene ATP 7B. Conclusions: Dystonia is the prominent neurological phenotype of WD in Oman. Clinical awareness and evaluation of close family members facilitated early diagnosis of this rare (but eminently treatable) disease.",teaching hospital;Oman;health care organization;diagnosis;university;Wilson disease;dystonia;dysarthria;mood disorder;consanguineous marriage;university hospital;autosomal recessive disorder;medical record;maintenance therapy;telephone;clinical feature;family history;male;early diagnosis;tremor;dysphagia;pyramidal sign;female;patient;human;mutation;exon;gene;phenotype;imaging;nuclear magnetic resonance imaging;copper;penicillamine;trientine;zinc sulfate;adenosine triphosphate,"Ramachandiran, N.;Alhabsi, A.;Al-Asmi, A.;Arunodaya, G. R.;Jacob, P. C.;Al-Azri, F.;Kashoob, M.;Joshi, S.;Bayoumi, R.",2012,September,http://dx.doi.org/10.1111/j.1468-1331.2012.03889.x,0,1,
1637,"An unexpected novel antioxidant activity for penicillamine, a classic copper-chelating drug for the treatment of Wilson's disease","Penicillamine (beta, beta'-dimethylcysteine) has been widely used clinically as a copper-chelating amino thiol drug for the treatment of copper overload in Wilson's Disease. In this study, we found that penicillamine provided marked protection against cytotoxicity in human fibroblasts induced by tetrachlorohydroquinone (TCHQ), a major toxic metabolite of the widely used wood preservative pentachlorophenol, while other classic copper chelating agents such as bathocuproine disulfonate do not. The autooxidation process of TCHQ yielding the reactive tetrachlorosemiquinone (TCSQ*<sup>-</sup>) radical was studied by ESR and UV-visible spectral methods. We found, unexpectedly, the formation of TCSQ*<sup>-</sup> radical was significantly inhibited and the autooxidation process of TCHQ was remarkably delayed by penicillamine in a concentration dependent manner. In contrast, no such effects were observed by the classic copper-chelating agent, or by penicillamine disulfide, the oxidized form of penicillamine. ESR and HPLC-MS studies showed that TCSQ*<sup>-</sup> radical was mainly reduced to TCHQ by penicillamine, which was concurrently oxidized to its corresponding disulfide form. These data suggest that the protective effects of penicillamine on TCHQ-induced cytotoxicity were not due to its binding of copper, but rather to its effective inhibition of the reactive TCSQ*<sup>-</sup> radical formation via an unusual redox pathway. This is the first report demonstrating an unexpected novel antioxidant activity for this copper-chelating drug, which might prove highly relevant to the biological activities of penicillamine.",antioxidant activity;society;Wilson disease;cytotoxicity;human;autooxidation;biological activity;fibroblast;protection;high performance liquid chromatography;copper;penicillamine;free radical;chelating agent;tetrachlorohydroquinone;penicillamine disulfide;pentachlorophenol;wood protecting agent;toxin;disulfide;thiol,"Zhu, B. Z.;Mao, L.",2012,01 Nov,http://dx.doi.org/10.1016/j.freeradbiomed.2012.10.303,0,0,
1638,Wilson disease in france: Follow-up of a cohort of 395 patients,"Background: One of the priorities of the French National Reference Center (FNRC) for Wilson Disease (WD), labeled end of 2005, is to improve the epidemiological knowledge of this rare disease. The objective of database for WD is to better define different profiles likely to evoke the diagnosis and to learn more about the disease evolution. Methods: Demographical, clinical, biological, radiological and therapeutic data of the 395 patients (aged from 1 to 77 years old) in the two reference centres (AP-HP and Lyon) and the 6 competence centres (Besanon, Lille, Aix/Marseille, Toulouse, Bordeaux and Rennes) of the FNRC for WD have been collected at time of diagnosis and/or during follow up. Results: The diagnosis has been set up most of the time after neurological symptoms (33 %), mean age of 23 years old, or hepatic symptoms (34 %) or with familial screening (20 %). The genetic investigation was not significant for 16 % of the families. D-Penicillamine has been the initial treatment for 85 % of the patients and still prescribed after 15 years of follow up for 44 % of the cases. The mean causes of death are hepatic failure, infections and hepatocellular carcinoma. Conclusion(s): As far as we know, this is the most important cohort of WD patients. However, it covers only about 1/3 of the French patients. In order to improve the registration of the WD patients in the database either at time of diagnosis or during follow up, the coordination of all healthcare professionals with a multidisciplinary approach must be encouraged. The French registry contributes greatly to Eurowilson database due to the number of patients included and followed.",Wilson disease;France;follow up;patient;human;neurology;epidemiology;diagnosis;data base;register;screening;rare disease;liver cell carcinoma;neurologic disease;death;competence;disease course;infection;liver failure;registration;health care personnel;penicillamine,"Girardot-Tinant, N.;Trocello, J. M.;Ruano, E.;Pelosse, M.;Woimant, F.",2012,October,http://dx.doi.org/10.1159/000343765,0,1,
1639,Coomb's negative hemolytic anemia and liver disease: A case of wilson disease,"Purpose: A 45-year-old black female presented with complaint of yellowing eyes, epigastric pain, nausea/vomiting and dark urine which began after undergoing a dilatation and curettage with hysteroscopy 3 weeks prior. She was found to have stable vital signs. Sleral icterus and conjunctival pallor were present. She had mild epigastric tenderness with no rebound or guarding. Labs showed a leukocytosis, macrocytic anemia, coagulopathy, non-anion gap metabolic acidosis, hypophosphatemia, transaminitis with hyperbilirubinemia and a markedly low alkaline phosphatase. Abdominal ultrasound showed no evidence of cholelithiasis or common bile duct dilatation. Empiric antibiotics were given and a transjugular liver biopsy was performed. Additional labs sent showed a cerruloplasmin of 6.7 g/dL and verified a Coomb's negative hemolytic anemia. She was evaluated for liver transplant, but was put on hold due to a possible pelvic infection. A 24-hour urine copper was sent for suspicion of Wilson Disease. However, her condition quickly deteriorated before the diagnosis was confirmed and she was empirically started on penicillamine 250 mg PO Q6h, vitamin B6 25 mg PO daily, zinc sulfate 220 mg PO TID and IV N-Acetyl Cysteine. Pre-treatment 24-hour urine copper was found to be 4056 mug. Based on her acute liver failure, markedly low alkaline phosphatase, low cerruloplasmin, Coomb's negative hemolytic anemia, elevated urine copper, and positive Rubeanic acid stain, the diagnosis of Wilson Disease was made. With no pelvic infection found, she was listed for liver transplant. Conclusion: Wilson Disease leads to copper accumulation that affects multiple organ systems, including the liver, brain, kidneys, and eyes. The diagnosis can be made by the presence of 2 of the following: positive family history, Kayser-Fleischer rings, Coombs-negative hemolytic anemia, low total serum copper and ceruloplasmin, elevated hepatic copper, and increased 24-hour urine copper. When Wilson Disease presents as acute liver failure, the goal of therapy is to induce a negative copper balance through promotion of urinary copper excretion and removal of tissue copper using copper chelators. Liver transplant is indicated in cases of acute liver failure or end stage liver disease when medical treatment options fail. (Figure presented).",liver disease;Wilson disease;college;gastroenterology;hemolytic anemia;urine;diagnosis;liver graft;acute liver failure;pelvic inflammatory disease;eye;therapy;hysteroscopy;metabolic acidosis;curettage;anion gap;hypophosphatemia;hypertransaminasemia;blood clotting disorder;macrocytic anemia;leukocytosis;pallor;tissues;bile duct dilatation;liver biopsy;jaundice;epigastric pain;common bile duct;cholelithiasis;family history;ultrasound;vital sign;brain;liver;hyperbilirubinemia;organ systems;stain;kidney;copper blood level;copper metabolism;excretion;female;end stage liver disease;copper;alkaline phosphatase;penicillamine;antibiotic agent;vitamin;zinc sulfate;acetylcysteine;acid;ceruloplasmin;chelating agent,"Barnes, T.;Kim, K.;Arrigo, R.;Tumer, G.;Peters, S.",2012,October,http://dx.doi.org/10.1038/ajg.2012.271,0,0,
1640,An unexpected novel antioxidant-like activity for the classic copper-chelating amino thiol drug penicillamine,"Penicillamine (beta, beta'-dimethylcysteine) has been widely used clinically as a copper-chelating amino thiol drug for the treatment of copper overload in Wilson's disease. In this study, we found that penicillamine provided marked protection against cytotoxicity induced by tetrachlorohydroquinone (TCHQ), a major toxic metabolite of the widely used wood preservative pentachlorophenol, in human fibroblasts, while other classic copper chelating agents such as bathocuproine disulfonate do not. The autooxidation process of TCHQ yielding the reactive tetrachlorosemiquinone (TCSQ*-) radical was studied by ESR and UV-visible spectral methods. We found, unexpectedly, the formation of TCSQ*- radical was significantly inhibited and the autooxidation process of TCHQ was remarkably delayed by penicillamine in a concentration dependent manner. In contrast, no such effects were observed by the classic copper-chelating agent, or by penicillamine disulfide, the oxidized form of penicillamine. ESR and HPLC-MS studies showed that the TCSQ*- radical was mainly reduced to TCHQ by penicillamine, which was concurrently oxidized to its corresponding disulfide form. These data suggest that the protective effects of penicillamine on TCHQ-induced cytotoxicity were not due to its binding of copper, but rather to its effective inhibition of the reactive TCSQ*- radical formation mainly through an unusual redox pathway, instead of the commonly recognized nucleophilic reaction. This is the first report demonstrating an unexpected novel antioxidant-like activity for this copper-chelating drug, which might prove highly relevant to the biological activities of penicillamine.",Penicillamine;Antioxidant-like Activity;Tetrachlorohydroquinone;Tetrachlorosemiquinone radical;society;autooxidation;human;cytotoxicity;biological activity;nucleophilicity;fibroblast;protection;Wilson disease;high performance liquid chromatography;antioxidant;thiol;copper;free radical;chelating agent;disulfide;penicillamine disulfide;pentachlorophenol;toxin;wood protecting agent,"Zhu, B. Z.;Mao, L.",2012,September,http://dx.doi.org/10.1016/j.freeradbiomed.2012.08.227,0,0,
1641,Impaired copper homeostasis in patients with hypertrophic cardiomyopathy,"Purpose: Hypertrophic Cardiomyopathy(HCM) is the commonest monogenetic inherited cardiac disorder, characterised by increased ventricular wall thickness, myocyte disarray and myocardial fibrosis. Recently, HCM has been associated with enhanced oxidative stress, which in turn has the potential to perpetuate hypertrophy and myocardial fibrosis. Myocardial copper and zinc imbalance are an important source of oxidative stress and have been shown to cause hypertrophic forms of cardiomyopathy in animal models. Furthermore, excess copper plays a pivotal role in Wilson's disease, an important HCM differential diagnosis. Copper chelation, the therapy in Wilson's disease, has recently been demonstrated to reverse LVH and organ fibrosis in several animal disease models and humans with Type 2 diabetes. Surprisingly, there is no published data concerning copper homeostasis in patients with HCM. We investigated whether patients with HCM have overt abnormalities in copper and zinc homeostasis. Methods: With ethical approval, we compared 20 randomly selected HCM patients from our local database with 18 matched healthy volunteers. Each participant provided 24 hour urine and fasting blood serum samples which were analysed for copper/caeruloplasmin/zinc using the highly sensitive and widely validated technique of Inductively Coupled Plasma Mass Spectrometry. Results: HCM patients exhibited significantly higher levels of serum copper and serum caeruloplasmin(Table 1). Serum zinc trended higher in healthy volunteers compared with HCM patients. There were no significant differences in urinary zinc or copper between the two groups. (Table Presented) Conclusion: HCM patients exhibit overtly altered copper homeostasis. Coupled with the previous observation of LVH and fibrosis regression induced by copper chelation therapy these findings provide a mechanistic basis for copper chelation therapy to be tested in HCM.",human;patient;homeostasis;hypertrophic cardiomyopathy;oxidative stress;heart muscle fibrosis;serum;fibrosis;normal human;chelation therapy;disease model;animal disease;Wilson disease;therapy;chelation;non insulin dependent diabetes mellitus;muscle cell;differential diagnosis;animal model;heart ventricle hypertrophy;diet restriction;cardiomyopathy;mass spectrometry;copper blood level;urine;zinc blood level;zinc urine level;data base;hypertrophy;diseases;copper;zinc;ceruloplasmin,"Potluri, R.;Roberts, N.;Miller, C.;Brooks, N.;Ray, S.;Cooper, G.;Schmitt, M.",2012,August,http://dx.doi.org/10.1093/eurheartj/ehs283,0,0,
1642,Status dystonicus in a case of Wilson's disease,"Purpose: Dystonia is a movement disorder characterized by sustained muscle contractions producing torsional and repetitive movements or abnormal postures. Status dystonicus is a generalized, intense and potentially fatal exacerbation of muscle contractures which is necessitated urgent hospital admission. It mainly affects patients with primary or secondary dystonia and is often triggered by fever, infection, trauma, surgery, abrupt introduction, withdrawal or change in medical treatment. We report one case of Wilson's disease presented with dystonic status. Method: A 49 year-old male with a previous diagnosis of Wilson's Disease treated trientine and zinc sulfate presented with generalized tonic clonic seizure. At time of admission he had hyperthermia up to 39 ordm; C. After control of seizure with diazepam and levetiracetam infusions the patient presented severe episodes of dystonia involved face and left arm and leg. Elevated serum creatine phosphokinase level was documented. Symptoms were resistant to conventional medication. Result: Gabapentin 900 mg/day, brought significant improvement and the patient remained clinically stable. Conclusion: Although status dystonicus is a rare but serious condition, prompt diagnosis is needed and gabapentin can be used to control severe episodes of dystonia.",Wilson disease;human;dystonia;patient;diagnosis;traumatology;infection;muscle contracture;fever;hyperthermia;muscle contraction;tonic clonic seizure;seizure;hospital admission;drug therapy;creatine kinase blood level;leg;arm;infusion;male;therapy;body posture;motor dysfunction;gabapentin;diazepam;etiracetam;zinc sulfate;trientine,"Cokar, O.;Mutlu, A.;Ozer, F. F.;Gurbuz, M.;Acar, H.;Genc, F.",2012,September,http://dx.doi.org/10.1111/j.1528-1167.2012.03677.x,0,0,
1643,A case of fulminant wilson's disease: Effect of plasmapheresis,"Background/Case Studies: Wilson's disease is an autosomal recessive disorder of dysfunctional copper transport that results in copper deposition into tissues including liver, kidney, brain, and cornea. Rarely, patients present with fulminant Wilson's disease (fWD) in which fulminant liver failure, DAT-negative hemolysis, and acute renal failure (ARF) lead to rapid clinical deterioration and is nearly always fatal without a liver transplant. Although therapeutic plasma exchange (TPE) has been recommended for fWD, the level of evidence is very low with only a few case reports available to address the efficacy of TPE. Here we report a case of fWD with successful liver transplantation following daily TPE. Study Design/Methods: A 21-year-old female presented with a 1 day history of dark colored urine, jaundice and fatigue. Physical examination and laboratory values demonstrated liver failure, DAT-negative hemolysis, Keyser-Fleischer rings, ceruloplasmin < 4 mg/dL, AST greater than ALT (123 and 40 IU/L, respectively), and 24 hour urine copper level of 4703 mug. fWD was diagnosed and Trientine and zinc acetate were started on day 1 of hospital admission. The patient also received 6 units of plasma for coagulopathy. Starting day 2, the patient received one plasma volume exchange daily with plasma as the replacement fluid. Additional plasma was not required after starting daily TPE except on day 4. Kidney function started to deteriorate from day 2 and continuous renal replacement therapy (CRRT) was started on day 4 following TPE #3. The patient received daily RBC transfusions on days 1-4 (total 7 units) for anemia due to intravascular hemolysis. Orthotopic liver transplantation was performed on day 6. Serum copper levels were measured on blood samples drawn at admission and after the final TPE. Medical records were reviewed to assess clinical response to therapy. Results/ Findings: Serum copper level at admission and following 4 consecutive daily TPE and 29 hours CRRT in addition to medications were 200 and 140 mug/dL, respectively. Hemoglobin was 7.3 g/dL at admission, 7.7-9.1 g/ dL on days 2-4 with daily RBC transfusions, then 8.5-9.0 g/dL on day 5. INR remained between 2.0 and 3.5 with TPE. Histology of the explanted liver showed cirrhosis with a very small amount of stainable copper in periseptal hepatocytes, and genetic analysis showed a heterozygous mutation of ATP7B (p.Q111X). Conclusion: Hemolysis continued during treatment with TPE alone but improved with the addition of CRRT. TPE, however, was an effective method to stabilize coagulopathy without increasing blood volume. Though serum copper decreased, it remains unclear how much of the copper was removed by TPE versus CRRT. Our case suggests that TPE alone is effective in stabilizing coagulopathy, but a combination of TPE with CRRT may be more efficient at stabilizing intravascular hemolysis in fWD.",plasmapheresis;Wilson disease;human;patient;copper blood level;hemolysis;plasma;continuous renal replacement therapy;blood clotting disorder;transfusion;liver transplantation;intravascular hemolysis;liver;urine;blood sampling;anemia;liquid;plasma volume;hospital admission;fulminant hepatic failure;case report;liver graft;female;deterioration;cornea;tissues;kidney function;liver failure;laboratory;acute kidney failure;brain;physical examination;medical record;fatigue;drug therapy;therapy;jaundice;histology;liver cirrhosis;liver cell;genetic analysis;mutation;blood volume;kidney;autosomal recessive disorder;erythrocyte;international normalized ratio;copper;isoprenaline;trientine;zinc acetate;ceruloplasmin;hemoglobin,"Choi, E. K.;Davenport, R. D.;Yamada, C.",2012,September,http://dx.doi.org/10.1111/j.1537-2995.2012.03833-1.x,0,0,
1644,Altered expression of metabolic nuclear receptor target genes in Atp7b<sup>-/-</sup> mice (Wilson disease mouse),"Wilson's disease is an autosomal recessive disease due to mutations in the Cu-transporting P-type ATPase (ATP7b) and results in excessive hepatic copper accumulation and often results in liver failure. The Atp7b<sup>-/-</sup> mouse animal model has increased hepatic copper levels similar to those of Wilson's disease patients as well as increased nuclear copper concentrations. Previous studies demonstrated that copper has a high affinity for the estrogen receptor DNA binding domain (ER-DBD), and incubation of the ER-DBD with copper results in loss of ER binding to response elements. Our hypothesis is that elevated hepatic copper concentrations result in decreased nuclear receptor activation due to disruption of zinc binding in the DNA-DBD of nuclear receptors. In vitro translation of RXR with 4-40 muM of copper (CuSO4) resulted in complete loss of FXR:RXR binding to the short heterodimer partner protein (SHP) and bile salt export pump (Bsep, canalicular bile acid transporter) promoters, and the addition of 40 muM zinc (ZnSO4) to the reaction restored binding to the SHP and BSEP promoters. Treatment of HepG2 cells with 5 mM CuSO4 decreased chenodeoxycholic acid mediated activation of BSEP mRNA expression. In Atp7b<sup>-/-</sup> mice at 6, 12, and 16-20 weeks Bsep and SHP mRNA expression were decreased 40% and 40-20% along with decreased binding of FXR to the Bsep and SHP mouse promoters in EMSA analysis. The mRNA expression of other nuclear receptor target genes were also decreased in the Atp7b<sup>-/-</sup> mice at 6, 12, and 16-20 weeks: HNF4a (Na<sup>+</sup>-taurocholate transporter protein, basolateral bile salt transporter, decreased 20%), LRH-1 (Cyp8b, required for cholic acid synthesis, decreased 40%; Abcg8, canalicular cholesterol transporter, decreased 20%), and TR (Spot14, regulation of triglyceride pools, decreased 40 - 20 %). The mRNA expression of HNF4a, and protein expression of RXR were unchanged in the Atp7b<sup>-/-</sup> mice. The basal mRNA expression of phase-I enzymes Cyp3a11 and Cyp2b10 were increased 2-fold (P= 0.057) in the Atp7b<sup>-/-</sup> mice, but activation with the constitutive androstane receptor (CAR) agonist TCPOBOP was attenuated in the knockout mice (20%, Cyp3a11 and 10% Cyp2b10) relative to wild-type littermates. These data show that the Wilson's disease mouse model has defects in nuclear receptor signaling that impair the regulation of genes involved in maintaining metabolic homeostasis in the liver.",mouse;Wilson disease;gene;society;promoter region;human;autosomal recessive disorder;model;pump;agonist;knockout mouse;homeostasis;liver;mutation;in vitro study;hypothesis;DNA responsive element;synthesis;DNA binding;protein expression;patient;animal model;mouse mutant;wild type;liver failure;gel mobility shift assay;cell nucleus receptor;copper;messenger RNA;zinc;protein;bile salt;heterodimer;constitutive androstane receptor;enzyme;bile acid;adenosine triphosphatase;triacylglycerol;cholic acid;estrogen receptor;cholesterol;taurocholic acid;chenodeoxycholic acid;dna,"Wooton-Kee, C. R.;Grusak, M. A.;Lutsenko, S.;Moore, D. D.",2012,,,0,0,
1645,Immunological study of a child with D-penicillamine-induced generalized myasthenia gravis,"Objective: D-penicillamine (D-Pen) is known to be a cause of drug-induced myasthenia gravis (MG), but its aetiology remains unclear. A reduction in regulatory T lymphocytes (Treg) has recently been reported in cases with non druginduced MG. We studied the immunological findings of a case with D-Pen-induced MG to clarify the pathogenesis of this disease. Design: Case report. A 12year-old- girl had been diagnosed with Wilson's disease at the age of one, and was administered D-Pen. She developed blepharoptosis and muscular weakness that varied daily, but not bulbar paralysis. Her titer of anti-acetylcholine receptor antibodies (AChR-Ab) was extremely high (1520nmol/L; normal range <0.04nmol/L). A Harvey- Masland test showed waning, which was improved by edrophonium administration. She was therefore diagnosed with D-Pen-induced generalized MG. D-Pen was discontinued, and zinc acetate and pyridostigmine were commenced to treat her Wilson's disease and MG, respectively. Although the patient's MG symptoms had disappeared 6months later, her abnormally high anti- AChR-Ab titer persisted. She was treated with immunoadsorption therapy to reduce the autoantibodies, followed by administration of immunosuppressants. We analyzed several immunological findings in our patient, including peripheral blood Treg count by flow cytometry based on the expression of CD4, CD25, and intracellular Foxp3. There was no correlation between anti-AChR-Ab titer and the patient's MG symptoms. The expression levels of her mean Treg/CD4+ lymphocytes (5.28+/-1.01%) were not significantly different from those of healthy controls. Conclusion: Our results support the notion that the pathogenesis of D-Pen-induced MG is different from that of non drug-induced MG.",child;human;neurology;myasthenia gravis;Asian;patient;regulatory T lymphocyte;pathogenesis;bulbar paralysis;muscle weakness;etiology;ptosis;lymphocyte;girl;flow cytometry;blood;female;myasthenia like syndrome;therapy;immunoadsorption;Wilson disease;case report;penicillamine;CD4 antigen;autoantibody;pyridostigmine;zinc acetate;edrophonium;cholinergic receptor antibody,"Nishimura, T.;Niimi, T.;Ishida, T.;Nakayama, Y.;Inaba, Y.;Naganuma, K.;Koike, K.",2012,June,http://dx.doi.org/10.1111/j.1469-8749.2012.04283.x,0,0,
1646,Presentation of wilsons disease in Pakistan: Is it different from the rest of world?,"Background: Wilsons disease (WD) is a rare autosomal recessive disorder of copper metabolism, with an average worldwide prevalence of approximately 1 in 30,000 people. Data regarding WD from Pakistan is not available hence we aim to determine the pattern of WD in Pakistan population and wanted to compare with international literature. Methods: Cross sectional study conducted at Aga Khan University Hospital Karachi. Results: Total of 47 patients seen,32 (68.1%) were male. Mean age (SD) was 26.6 (9.97) yrs. Most common presentation was hepatic; 22 (46.8%), neurological; 17 (36.2%) and rest 8(17%) were presented with psychiatric symptoms. Ceruloplasmin levels was reduced (<0.25 g/dl) in 39 (86.6%), reduced serum Cu in 32 (68.1%). 24 h urinary Cu was raised in only 22(47.6%).Slit Lamp examination for Kayser-Fleischer (KF) rings was done on 15 (31.9%) patients and only 9 (60%) had KF rings. Out of these 9 patients with KF ring positive, 8 (88.8%) had neurologic disease. Mean AST)/ALT ratio was 1.92 and median Alkaline Phosphatase/Total Bilirubin ratio was 79.30 (IQR 35.05; 166.50). 31 (65.4%) patients were given combination of D-Penicillamine and Zinc (Zn), 11(23.1%) were given only D-Penicillamine and only 5 (11.5%) were on Zn alone. Only one patient with decompensated liver disease underwent liver transplant. Conclusions: Patients with WD present slightly later in adulthood in our population and hepatic presentation is the most common. The disease presentation and biochemical parameters in Pakistan are not different from the rest of the world.",Wilson disease;Pakistan;Asian;liver;human;patient;population;slit lamp;serum;prevalence;neurologic disease;mental disease;male;liver graft;decompensated liver cirrhosis;university hospital;cross-sectional study;adulthood;parameters;copper metabolism;autosomal recessive disorder;zinc;penicillamine;ceruloplasmin;bilirubin,"Parkash, O.;Ayub, A.;Jafri, W.;Alsihah, S. H.;Hamid, S.",2012,January,http://dx.doi.org/10.1007/s12072-011-9333-4,0,1,
1647,Cerebral cortex and white matter lesions in Wilson's disease,"Objective: To evaluate the clinical features and imaging findings in Wilson's disease (WD) with cerebral cortex and white matter lesions. Background: The cerebral cortex and white matters come to be eventually involved in WD patients during the long disease course. Occasionally, however, the cerebral symptoms such as seizure are the initial symptoms with prominent cerebral lesions. In those cases, the diagnosis of WD is difficult and the clinical course may be different from usual cases of WD. Methods: We screened WD patients who showed cerebral lesions initially in our department from 1964 to 2011, two patients showed cortical-subcortical lesions. We analyzed the clinical features and courses of these patients. Results: Two patients out of 17 WD patients in our department had cerebral lesions. case1: A 22-year-old man) initially presented with progressive gait disturbance, hand tremor, and psychiatric disturbance. Brain MRI showed high T2 weighted signal in white matter of bilateral frontal lobes (Rt >Lt) and basal ganglia, and frontal lobes cortex are enhance with gadolinium. FDG-PET showed accumulation in the cortical-subcortical lesions in the right frontal lobe, which made us first to suspect the diagnosis tumor. However, the possibility of WD was considered based on high echoic abnormalities in the liver. Mutation in ATB7B (c.2304insC) provided definitive diagnosis of WD. He was treated with trienthine. Nevertheless, his clinical symptoms and MR image exacerbated in 2 months. Therefore, zinc acetate was given secondly. After that, his clinical symptoms were not no changed. case2: A 20-year-old man initially complained of stuttering, hand tremor, and euphoric mood for 6 years. Brain CT revealed low density areas in the left frontal lobe. He was treated with D-penicillamine. After 3 month, he developed seizure and CT showed that left frontal lesion was more extensive. Conclusions: Previously, the cerebral lesion was reported to occur in 25% WD patients during the clinical course. In our department, about 10% of the patients presented initially with cerebral lesions. In such patients, the diagnosis of WD was difficult and chelate treatment is ineffective. We should take into account the possibility of WD in patients with tremor and psychiatric disorders, or even with prominent cerebral lesion involving the basal ganglia.",motor dysfunction;white matter lesion;brain cortex;Wilson disease;Parkinson disease;human;patient;brain damage;frontal lobe;diagnosis;disease course;clinical feature;white matter;hand tremor;seizure;brain;basal ganglion;male;liver;tumor;imaging;mutation;mental disease;gait;density;tremor;mood;stuttering;nuclear magnetic resonance;nuclear magnetic resonance imaging;gadolinium;chelate;penicillamine;zinc acetate,"Tanaka, N.;Hanajima, R.;Terao, Y.;Goto, J.;Tsuji, S.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,0,
1648,Myeloneuropathy secondary to excessive copper removal in Wilson's disease,"Objective: Case report. Background: Treatment of Wilson's disease (WD) focuses on removing excess copper from the body and preventing it from reaccumulating. Paradoxically, there have been reports of neuropathy and myeloneuropathy secondary to copper deficiency induced by excess removal. Methods: Case report. Results: Patient was a 36 years-old male with WD diagnosed with 20 years-old. The main clinical picture was characterized by generalized dystonia, bradikynesia, hiperreflexia, bilateral Babinski sign and freezing of gait. He was admitted in our department following a 6 months history of worsening of gait instability, with frequent falls, and numbness of the hands and feet. He presented an algic hypoesthesia with socks and gloves distribution, postural and vibratory hypoesthesia of the lower limbs, gait ataxia and freezing. The neuroaxis MRI detected a bilateral hiperintensity on T2 WI without correspondent abnormal signal on T1, involving a long segment of the posterior dorsal cord. There was no contrast enhancement on post-gadolinium images or expansion of the spinal cord. Lenticulocaudate copper deposition and putamen gliosis were also observed. The electromyography showed a sensoriomotor peripheral neuropathy. The analitical studies revealed serum copper 10,2 mg/dL (69,9- 152,5), urinary copper 0,64 mumol/24h (0,78), serum zinc 14,7 mumol/L (12-20), Hb 8,2 g/dL, Leucocytes 10,63x109/L, Platelets 624x109/L. Alternative causes of myelopathy and polineuropathy were excluded. A causal relationship between copper deficiency and myeloneuropathy was classified as probable. Trientine (500 mg/d) and zinc sulfate (330mg/d) were suspended, and zinc acetate 100 mg/d was started. After 3 months of follow-up, a mild clinical recovery was documented. Conclusions: This case alerts to the neurological consequences of excessive copper expoliation during prolonged WD treatment. Myeloneuropathy symptoms may mimic the manifestations of progressive WD, with worsening postural instability and gait impairment. The awareness of the risks associated with excess copper removal associated with a more frequent monitoring of copper levels may prevent this complication.",motor dysfunction;Wilson disease;Parkinson disease;human;gait;hypesthesia;case report;freezing;copper deficiency;patient;gliosis;peripheral neuropathy;putamen;spinal cord;electromyography;contrast enhancement;ataxia;follow up;risk;monitoring;paresthesia;neuropathy;copper blood level;Babinski reflex;leg;spinal cord disease;thrombocyte;glove;zinc blood level;generalized dystonia;male;nuclear magnetic resonance imaging;copper;trientine;gadolinium;zinc sulfate;zinc acetate,"Teodoro, T.;Neutel, D.;Geraldo, F.;Rosa, M. M.;Albuquerque, L.;Ferreira, J. J.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,0,
1649,Chelation-therapy induced restless legs syndrome in Wilson's disease: A novel complication following liver transplantation,"Objective: To describe a novel side effect of copper chelation therapy in a patient with Wilson's disease post liver transplantation. Background: A 52 year old man with genetically confirmed Wilson's disease was started on D-penicillamine therapy as a teenager. He tolerated copper chelation well, but developed decompensated liver disease, and required transplantation. Following liver transplantation surgery, chelation therapy was discontinued. Ten months post transplantation he presented with progressive dysarthria, bradykinesia and cogwheel rigidity. D-penicillamine therapy was resumed. Methods: Serial biochemical results were collated from several hospitals that the patient attended. The stoichiometry of penicillamine- transition metal reactions and the dissociation constants of these reactions were reviewed. Results: Following liver transplantation, the biochemical abnormalities associated with Wilson's disease normalise. However, neuropsychiatric symptoms have a variable outcome. In this case, chelation was resumed due to progressive neurological symptoms, but in a patient with essentially normal copper biochemistry. Copper is preferentially excreted by D-penicillamine in Wilson's disease, as these patients are copper loaded. As the mass of copper decreases, other transition metals having a lower affinity constant, but being in relatively greater abundance than copper, will be excreted. In this patient, iron deficiency developed commensurate with re-introduction of D-penicillamine treatment, resulting in disabling restless legs syndrome. Conclusions: Use of chelating agents in Wilson's patients post liver transplantation can lead to transition metal deficiencies. This arises as the copper levels normalise and the dissociation constant for the reaction is invariable. This is the first report of penicillamine induced restless legs syndrome in a patient with Wilson's disease.",restless legs syndrome;chelation therapy;liver transplantation;motor dysfunction;Parkinson disease;Wilson disease;human;patient;transplantation;dissociation constant;chelation;therapy;stoichiometry;hospital;rigidity;bradykinesia;dysarthria;male;decompensated liver cirrhosis;side effect;iron deficiency;neurologic disease;adolescent;copper;penicillamine;transition element;chelating agent,"O'Brien, M.;Counihan, T.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,0,
1650,Epilepsy in Wilson's disease (WD),"Objective: To evaluate patients of WD with epilepsy. Background: WD is an autosomal recessive treatable disorder of copper accumulation and copper toxicity having protean manifestations involving mainly brain and liver. Neurologically it manifests as a movement disorder, with abnormalities of speech, tremor, incoordination and dystonia being common features. Epilepsy is not a common presentation of WD. Methods: We evaluated 31 patients of WD and found 6 of them having epilepsy. These patients underwent electroencephalogram (EEG) apart from the detailed history, general and neurological examination, slit lamp examination for Kayser-Fleischer ring in cornea, routine biochemical and copper studies (serum ceruloplasmin, 24 hour urinary copper and serum copper), and neuroimaging. Results: Of the 6 (19.4%) patients having epilepsy, 4 (66.7%) were male and rest female. 4 (66.7%) patients were in the juvenile group(<=18 years age)while other 2 (33.3%) were in the adult group (>=18 years age). The 4 juvenile patients presented with predominant dystonic features and the 2 adult patients had both neurological and psychiatric features. 4 (66.7%) patients had complex partial seizures with secondary generalization while 2 (33.3%) had generalized seizures. 1 (16.7%) patient also had occasional myoclonic jerks. EEG was abnormal in all 6 patients with theta background and focal and generalized discharges seen. In 4 (66.7%) patients seizures started before initiating decoppering therapy while in 2 patients it started later. All the patients responded well to antiepileptics. The response of the WD itself to treatment was more variable with 2 (33.3%) patients showing improvement, 3 (50%) patients showing initial deterioration with slight improvement and 1 (16.7%) patient deteriorated and died. Conclusions: The prevalence of epilepsy in our study is 19.4%. It is around 30 times higher than the prevalence of epilepsy in general population and hence it is unlikely to represent a chance relationship. It may result either due to direct toxicity of copper (probably by inhibition of membrane ATPase) or due to pyridoxine deficiency during penicillamine use or due to a metabolic encephalopathy like state. Although prognosis of epilepsy in WD is comparable to that in general population but how much it affects the prognosis of WD needs evaluation of a larger series of such patients.",epilepsy;motor dysfunction;Wilson disease;Parkinson disease;human;patient;population;adult;juvenile;toxicity;prevalence;prognosis;electroencephalogram;female;cornea;autosomal recessive inheritance;slit lamp;liver;ceruloplasmin blood level;speech;pyridoxine deficiency;membrane;neurologic examination;neuroimaging;dystonia;tremor;deterioration;brain;therapy;seizure;grand mal seizure;complex partial seizure;diseases;metabolic encephalopathy;male;copper blood level;copper;penicillamine;adenosine triphosphatase,"Kumar, N.;Joshi, D.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,1,
1651,Spectrum of movement disorders in Wilson's disease and its response to penicillamine therapy,"Objective: To report the spectrum of movement disorders in Wilson's disease (WD) and the predictors of response to penicillamine therapy. Background: Movement disorder is although a dominant feature in neurologicWD, but there is paucity of study regarding its spectrum and response to penicillamine. Methods: Consecutive neurological WD patients were subjected to detailed history and clinical examination. The type, extent and severity of movement disorders were recorded. Complete hemogram, serum chemistry, ceruloplasmin, copper, urinary copper, ultrasound abdomen, and cranial MRI were done. Severity of WD assessed in a 0-3 scale. Following penicillamine, patients were followed up at 3 months follow up and considered worsened if there was > 1 grade deterioration. Results: 67 patients with neurological WD were included whose median age was 13 (4-41) years and 14 were females. 63 patients had movement disorders; dystonia in 17, tremor in 2 and the remaining had dystonia in association with tremor in 21, myoclonus in 7, choreoathetosisin 11 and chorea and tremor in 5 patients. MRI was abnormal in 79%; 87% had corpus striatum involvement and 56% each had brainstem, thalamus and globuspallidus involvement. At 3 months of treatment 22(32.8%) patients deteriorated neurologically and related to family history of WD (p= 0.03), low leucocyte count (p= 0.03), chronic liver disease (CLD) on ultrasound (p= 0.008).Out of 38 patients with CLD, 19(86.4%) patients had deterioration whereas 90%(26/29) patients without CLD did not have deterioration. The duration of illness (p= 0.47), severity of movement disorder (p= 90), serum creatinine (P=0.97), albumin (p= 0.87), bilirubin (p= 0.40), transaminase (p= 0.78), copper (p= 0.93), urinary copper (p= 0.70) and number of MRI lesions (p= 0.60) were not related to deterioration. The urinary copper excretion was significantly increased at 3 months compared to baseline in the deterioration group than those without deterioration (mean 53.3 Vs - 3.2, p= 0.005). Conclusions: Movement disorder is the presenting feature in 94% patients with neurological WD and 34% patients deteriorate following penicillamine especially those with family history of WD, lower leucocyte count and chronic liver disease.",motor dysfunction;therapy;Wilson disease;Parkinson disease;human;patient;deterioration;tremor;leukocyte count;ultrasound;chronic liver disease;family history;dystonia;nuclear magnetic resonance imaging;serum;clinical examination;female;myoclonus;follow up;excretion;creatinine blood level;diseases;abdomen;thalamus;brain stem;corpus striatum;chorea;penicillamine;copper;aminotransferase;albumin;ceruloplasmin;bilirubin,"Kalita, J.;Chandra, S.;Kumar, V.;Misra, U. K.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,0,
1652,Behavior of speech in Wilson's disease,"Objective: This study has analyzed the Wilson's disease patients' speech behavior. Background: Wilson's disease is described as autosomal recessive and is characterized by deposition of copper mainly in the liver and central nervous system. Among neurological manifestations of Wilson's disease, the problems of speech can occur, but they are little known and described, what makes it difficult the elaboration of efficient intervention procedures. Methods: Thirty patients who are diagnosed and treated in the Neurology Department, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil, 16 males and 14 females aged between 19 and 58 years old, are all under medical treatment (D-penicillamine or zinc sulfate) in variable doses. They were also submitted to phonoaudiological evaluation that consists on perception auditive qualified analysis of speech behavior. Results: Analysis showed 7 (seven) patients (23,2%) without speech alterations, 9 patients (30%) with anarthria and 14 patients (46,67%) with dysarthria. In this last group, 1 patient (3,33%) in low level, 8 patients (26,66%) in moderate level and 5 patients (16,66%) in accentuated level. Conclusions: These results suggest that there isn't a standard in the disease manifestation as well as clinical speech expression is variable. So, to improve the comprehension of Wilson's disease's several clinical forms, treatment and rehabilitation, systematic studies that correlate clinical signs and symptoms with functional tests and laboratory and image exams are necessary.",speech;motor dysfunction;Parkinson disease;Wilson disease;human;patient;liver;autosomal recessive inheritance;therapy;university;dysarthria;Brazil;female;school;laboratory;neurology;physical disease by body function;rehabilitation;comprehension;procedures;central nervous system;male;penicillamine;copper;zinc sulfate,"Estevo, A. D.;Carvalho, M. J.;Machado, A. A. C.;Barbosa, E. R.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,1,
1653,Analysis of smell in Wilson's disease,"Objective: Analysis of smell in Wilson's disease patients. Background: Wilson's disease, described by Samuel Alexander Kinnier Wilson, in 1912, is an inherited autosomal recessive disease of copper metabolism. Affected people have excessive deposition of copper in the liver which can be fatal if not recognized because of defective excretion of copper in the bile. Methods: Sniffin' Sticks test (with 16 pens) was used to smell evaluation. In the study, 60 controls were analyzed (24 females and 36 males, age average 33,81 years old) and 64 patients diagnosed with Wilson's disease (29 females and 35 males, age average 31,28 years old). All patients with Wilson's disease are under medical treatment (Trientine, D-penicillamine or zinc sulfate), 26 patients (13 females and 13 males) have only hepatic manifestation and 38 patients (16 females and 22 males) have hepatic and neurological manifestation. In statistic analysis, Right Fisher and Mann- Whitney tests were used. Results: Wilson's disease patients with only hepatic manifestation and patients with neurological manifestation are similar statistically, but there are differences for five variants (mint, banana, lemon, anise and fish) and for Sniffin' Sticks Total variable between Wilson's disease patients and the control group. Conclusions: Our study demonstrated the difference between Wilson's disease patients abd control group in the identification of specific smells (mint, banana, lemon, anise and fish).",motor dysfunction;odor;Wilson disease;Parkinson disease;human;patient;male;female;banana;lemon;fish;anise;control group;rank sum test;bile;excretion;autosomal recessive disorder;liver;therapy;copper metabolism;copper;zinc sulfate;penicillamine;trientine,"Carvalho, M. J.;Machado, A. A. C.;Barbosa, E. R.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,0,
1654,Wilson's disease: Follow-up studies in a cohort of 135 neuro- Wilson's patients for more than a decade,"Objective: To characterise the presenting features of Wilson's disease (WD) patients and the response to treatment. Background: WD is an inherited metabolic disorder causing mainly neuro-psychiatric, and hepatic dysfunctions. Untreated, it causes severe morbidity and case fatalities. Long-term clinical follow- up data are limited in literature. Methods: 135 consecutive patients diagnosed as Neuro-WD in the Movement Disorder Clinic of a tertiary care centre of India (Bangur Institute of Neurology) were included. Study period was from June, 1996 to December, 2011. This is both a retrospective (28) and a prospective study (107). The diagnosis of WD was made by Sternlieb's criteria. KF ring was positive in all, Data was compiled in semistructured proforma. Treatment was with D-penicillamine and zinc salts. Additionally, other medications were given as required. The patients were followed up at regular intervals. Results: Mean age of onset was 11.79 years; (males: females 584:51). Mean duration of disease before diagnosis was 15.30 months. Family history of WD was present in 22.96%; consanguineity in 10.37%. History of jaundice was present in 47.41%; hepatic disease in 44.44%. Presenting features were: dysarthria- 90.44%, parkinsonism- 81.62%, dystonia- 90.4%, tremors- 51.11%, choreo-athetosis in 11.85%, ataxia- 11.76%, sialorrhoea- 77.21%, dysphagia- 55.88%, seizure- 17.16%, psychiatric- 62.31%; arthralgia/arthritis- 3.7%, myopathy- 7.5%, amenorrhoea/oligomenorrhoea - 7.5%, darkening of skin colour- 11.6%, bleeding disorders- 7%. Mean time for improvement was 7.11 months. 14.58% patients initially worsened on D-penicillamine which didi not recur on restarting the drug at lower doses. Dysarthria and residual dystonia were the commonest residual deficits (86% and 90.4% respectively). Behavioral abnormalities often worsened even though the physical symptoms improved. KF ring disappeared in 7.40% and urinary copper levels normalized in 11.11%. 33.33% of patients were drug defaulters, at least once. 7.407% became symptom free;15.55%- had residual symptoms but were meaningfully employed; 25.92%- had symptoms but could do ADL; 24.44%- partially dependent; and 16.30%-severely dependent. Mortality was 10.37%. Conclusions: Dystonia and dysarthria were the commonest features. Early treatment leads to better results. Treatment needs to be individualized. Drug defaulters rapidly worsened.",human;follow up;patient;motor dysfunction;Wilson disease;Parkinson disease;dysarthria;dystonia;diagnosis;morbidity;female;bleeding disorder;color;mortality;drug therapy;onset age;fatality;myopathy;seizure;liver dysfunction;hypersalivation;athetosis;tremor;prospective study;parkinsonism;dysphagia;neurology;liver disease;skin;India;jaundice;family history;male;tertiary health care;hospital;metabolic disorder;penicillamine;zinc derivative;copper,"Bagchi, M.;Das, S. K.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,1,
1655,Patients with free copper toxicosis in Wilson's disease should be treated with zinc from the beginning,"Objective: Make known that (1) Wilson's disease (WD) is not a suitable name for free copper toxicosis that is treatable (2) Zinc is an appropriate choice for the treatment of copper toxicosis. Background: Patients with WD have been abusively treated with chelators, which aimed at excretion of the accumulated copper. It has taken 50 years to be generally accepted that chelators are unscientific and irrational. On the contrary, zinc reduces intestinal copper absorption, resulting in reduction of copper intoxication. Fundamentally, it is impossible to conduct a comparative clinical trials for a rare disease. Consequently, it should be learned from case reports and tested expert opinion based theories. Methods: We conducted a retrospective observational study as the best available method on three cases with free copper intoxication in WD treated on zinc monotherapy: (1) a 12 years old boy with hypokinesia, dysarthria, tremor, dystonia and involuntary movements, (2) a 24 years old girl with progressive tremor, gait disturbance and torticollis and (3) a severely ill 10 years old girl presented abruptly with hemolytic anemia indicated for liver transplantation. Although, the second patient, initially presented with decompensated hepatitis, had been treated with penicillamine for about 15 years, newly deteriorated with neurological symptoms. The clinical situation and biochemical parameters like urine copper and liver function tests along with physical examination were frequently evaluated. Results: The first patient with neurological and degenerative symptoms significantly improved biochemically in a few months and also clinically in about 12 months on 150 mg zinc. The symptoms of the second patient particularly disappeared in about a month on 100 mg zinc. The most amazing outcome was with the third patient who needed an urgent liver transplantation and became out of list on a merely 2 weeks of 125 mg zinc monotherapy with impressive clinical improvement. All became free of symptoms. Conclusions: The aim in management of WD should be the prevention of free copper intoxication. Zinc is the treatment of choice for treating free copper intoxication in WD from the beginning, which should be of educational value to the physicians to treat the patients through tested evidences not on expert based pseudoscientific thesis.",human;motor dysfunction;intoxication;patient;Parkinson disease;Wilson disease;tremor;monotherapy;liver transplantation;girl;female;rare disease;gait;excretion;involuntary movement;observational study;neurologic disease;urine;liver function test;prevention;physician;torticollis;hemolytic anemia;case report;dystonia;dysarthria;hypokinesia;clinical trial (topic);hepatitis;boy;parameters;male;physical examination;absorption;zinc;copper;chelating agent;penicillamine,"Avan, A.;Azarpazhooh, M.;Kianifar, H.;Hoogenraad, T.",2012,June,http://dx.doi.org/10.1002/mds.25051,0,0,
1656,Elastosis perforans serpiginosa with an atypical and widespread presentation,"Introduction and objectives. Elastosis perforans serpiginosa (EPS) is a rare skin disease in which there is a transepithelial elimination of connective tissue elements such as elastic fibers from papillary dermis. There are three different types of this disease: idiopathic, reactive and drug-induced. The reactive forms are associated with other diseases such as Down's syndrome, Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, scleroderma and pseudoxanthoma elasticum. The drug-induced form is seen in about 1% of the patients treated with D-penicillamine. This drug is used in diseases such as Wilson's disease and homocystinuria. The most frequent clinical presentation are small keratotic papules that usually affect face, neck, trunk and upper limbs. Topical retinoids, corticoids, calcineurin inhibitors and different types of laser have been used to treat this disease with variable response rates. (Figure Presented) We report the case of a 16-year-old boy with Down's syndrome presenting an atypical and widespread case of elastosis perforans serpiginosa. Report of the case. A 16-year-old boy with Down's syndrome was refered to our Department presenting large plaques on the anterior part of both thighs. The plaques were erythematous with a depressed center and elevated hyperkeratosic edges. No other skin lesions were observed. A skin biopsy from one of the edges was performed that showed acanthosis and a transepithelial elimination of elastic fibers that stained positively with Orcein. This histological features were consistent with the diagnosis of elastosis perforans serpiginosa. The patient was treated with topical betamethasone and calcipotriol without good response. Conclusions. We report a case of elastosis perforans serpiginosa in a 16-year-old boy with Down's syndrome. EPS usually affects children and young people, from 6 to 20 years old, and lesions are located on face, neck and arms. The clinical presentation in this child was widespread and atypical, with large erythematous plaques affecting the anterior part of both thighs with no other lesions on the face or arms. The incidence of EPS in patients with Down's syndrome is higher than in general population. A possible explanation to this could be that patients with Down's syndrome have an alteration in the connective tissue and elastic fibers such as premature skin aging and post-folliculitis anetoderma. (Figure Presented).",Elastosis perforans serpiginosa;Down's syndrome;Elastic tissue abnormalities;elastosis;society;elastic tissue;dermatology;Down syndrome;human;patient;boy;elastic fiber;arm;male;diseases;neck;connective tissue;thigh;child;Ehlers Danlos syndrome;osteogenesis imperfecta;dermis;Marfan syndrome;homocystinuria;pseudoxanthoma elasticum;anetoderma;skin disease;scleroderma;papule;skin defect;skin biopsy;acanthosis;diagnosis;laser;population;cutaneous parameters;folliculitis;Wilson disease;penicillamine;betamethasone;retinoid;corticosteroid;calcipotriol;calcineurin inhibitor,"Hernandez Ruiz, E.;Garcia, A.;Navarra, E.;Ferrando, J.",2012,March,,0,0,
1657,Successful pregnancy outcome in a woman presenting with Wilson's disease complicated by liver cirrhosis: A case report,"Objective: To report a successful pregnancy outcome in a lady with Wilson's disease, managed in a UK District General Hospital setting. A review of literature is presented along with the case. Methods: Prospective follow up of the index case throughout her pregnancy, birth and postnatal period. A retrospective review of current evidence was undertaken using MEDLINE and EMBASE databases. Results: A 28 year old primigravida with Wilson's disease diagnosed in her late teens, presented to us at 14 weeks of gestation. She suffered from liver cirrhosis. Preconceptually her disease was stable on zinc therapy, which required a change to trientine at 20 weeks of gestation because of her iron deficiency, attributed partly to the zinc therapy. A close multi-disciplinary approach involving Obstetricians, Haematologists and Hepatologists was undertaken. Her pregnancy was complicated initially with several episodes of self-terminating epistaxis, which settled by the third trimester. She had an induction of labour for suspected obstetric cholestasis at 38 weeks of gestation and gave birth to a healthy male infant weighing 3014 g. The delivery was complicated by major postpartum haemorrhage of 1500 mL, which was managed successfully. She recovered to her stable prepregnancy condition. Conclusions: This case serves to highlight the importance of appropriate use of multidisciplinary team approach and utilising limited resources in the management of a challenging medical disorder in pregnancy. It illustrates the difficulty in treatment during pregnancy and the fine line between overtreatment and under treatment. Wilson's disease is a rare condition with limited evidence to aid management decisions.",human;female;liver cirrhosis;pregnancy outcome;college;case report;Wilson disease;pregnancy;therapy;perinatal period;United Kingdom;epistaxis;follow up;general hospital;iron deficiency;third trimester pregnancy;cholestasis;boy;primigravida;diseases;postpartum hemorrhage;data base;male;zinc;trientine,"Ryan, L.;Kapoor, T.;Muslim, I.",2012,June,http://dx.doi.org/10.1111/j.1471-0528.2012.03376.x,0,0,
1658,Children with Wilson disease: Proton magnetic spectroscopy findings,"Background and aim: Neurological involvement is less common in Wilson disease (WD) pediatric patients than in adults. Therefore, a subclinical neurological involvement can not be excluded. Brain spectroscopy (MRS) has been used as a tool to provide clinically useful metabolic information about WD neurologic deterioration. The aim of our study was to determine the brain metabolic changes due to WD by using MRS in patients with a mild liver disease, treated since childhood. Material and methods: Twenty-two patients (15males) with established diagnosis of WD (mean age at diagnosis6,6 years; range1,8-14,4) were enrolled. Diagnosis of WD was established in presence of at least two of the following features: ceruloplasmin level <20 mg/dl, basal urinary copper level >100 mcg/24 hours, urinary copper level after penicillamine challenge test >1575 mcg/24 hours, liver copper level >250 mcg/g of dry weight. All patients had a mild liver disease at onset, with subtle neurological signs in 8 cases (36.4%). All the twenty-two patients were examined with MRS in the basal ganglia (BG), occipital cortex (POC) and frontal white matter (FWM). Ratio of the following metabolites were calculated in relation to creatine (Cr): N-acetylaspartate (NAA) and myo- inositol (mI). The mean peak line width was measured on each spectrum. At the time of MRS evaluation, the mean duration of disease was13.7 years (range2.1-24.1) and the mean age was19.6 years (range9.8-34.4). Results: Metabolic ratios at MRS in our cohort resulted in the normal range. Compared with group of patients with hepatic symptoms, the group with concomitant subtle neurological symptoms had not significantly decreased NAA/Cr ratio (GB: 82.7% versus 89.6%; POC:101.2% versus116.6%; FWM: 89.1% versus 86.2%) and increased mI/Cr ratio (GB:26.9% versus 22.7%; POC: 34.8% versus 34.9%; FWM:46.4% versus42.9%) in the three studied areas. Conclusions: It is known that in adult WD patients with neurologic signs, MRS changes is unequivocally associated with reduction of NAA/Cr ratio assigned to neuronal loss, and increased level of mI/Cr ratio related to gliosis and inflammation. The absence of reduced levels of NAA/Cr and increased levels of mI/Cr in our cohort seems indicate that an early therapy may prevent neuronal loss, gliosis and inflammation in brain areas, also in children with subtle neurologic signs at onset.",gastrointestinal disease;human;Wilson disease;spectroscopy;health care organization;child;patient;neurologic disease;brain;inflammation;adult;liver disease;gliosis;diagnosis;therapy;metabolite;white matter;occipital cortex;basal ganglion;male;childhood;dry weight;liver;provocation test;deterioration;proton;copper;penicillamine;ceruloplasmin;inositol;n acetylaspartic acid;creatine,"Ranucci, G.;Liccardo, D.;Puoti, G.;Di Dato, F.;Tufano, M.;Venturino, D.;Iorio, R.",2012,March,http://dx.doi.org/10.1016/S1590-8658%2812%2960532-5,0,0,
1659,Pancreatic involvement in children with Wilson disease on long-term zinc therapy,"Background and aim: Wilson disease (WD) is a disorder characterized by an accumulation of copper in various organs, specially liver. Treatment is based on the use of copper chelators and zinc. In adult WD patients treated with zinc a frequent increase in the serum amylase and lipase, without the symptoms of pancreatitis, has been reported. The aim of our study was to evaluate pancreatic enzymes in WD children on long-term zinc therapy. Material and methods: Fourty-three WD patients (28 males; mean age at diagnosis6.1 years, range1.1-20.9) were retrospectively evaluated. The patients were symptom-free. Diagnosis of WD was established in presence of at least two of the following features: ceruloplasmin level <20 mg/dL, basal urinary copper (UCu) level >100 mcg/24 hours, UCu after the penicillamine challenge test >1575 mcg/24 hours, liver copper level >250 mcg/g of dry weight. Thirty-two patients (24 males) on long-term (median duration12 years, range 3-25) zinc therapy (25 or 50 mg elemental zinc two or three times daily according to body weight and age) were investigated. Compliance to therapy was evaluated on the basis of clinical history and serum and urine copper and zinc levels. In all patients, amylase and lipase serum levels were analyzed during the course of zinc therapy. Results: Twenty-seven patients (84%) maintained normal ALT level on zinc therapy. According to UCu excretion (37+/-2mcg/24 h) at the end of the follow-up, all patients had a good compliance to therapy. Pancreatic serum levels were normal before the initiation of zinc therapy in all. Nine patients (28%) showed on zinc therapy hyperamylasaemia (219+/-44UI/L) and7 (22%) hyperlipasemia (110+/-30UI/L), without clinical and radiological signs of pancreatitis. Only a24 year-old adolescent (3%) showed an attack of acute symptomatic pancreatitis, with high levels of amylase and lipase (300UI/L and220UI/L, respectively) after78 months of zinc therapy. Common causes of pancreatitis other than zinc were ruled out. Conclusions: This study confirms that also in childhood most WD patients chronically treated with zinc show benign pancreatic hyperenzymemia. In contrast with previous reports, acute pancreatitis may occur.",gastrointestinal disease;human;Wilson disease;therapy;health care organization;child;patient;pancreatitis;male;liver;blood level;acute pancreatitis;childhood;follow up;excretion;diagnosis;urine;serum;body weight;dry weight;provocation test;amylase blood level;adolescent;adult;diseases;zinc;copper;triacylglycerol lipase;amylase;penicillamine;ceruloplasmin;pancreas enzyme;chelating agent,"Ranucci, G.;Tufano, M.;Liccardo, D.;Di Dato, F.;Puoti, G.;Salvatori, M.;Iorio, R.",2012,March,http://dx.doi.org/10.1016/S1590-8658%2812%2960410-1,0,0,
1660,Long term zinc therapy inwilson disease children with mild liver disease,"Background and aim: Wilson disease (WD) is a disorder of copper metabolism. In the pediatric age most cases have a hepatic presentation. It is widely accepted that penicillamine is the first-choice therapy for children with liver disease while zinc is indicated in presymptomatic patients and as maintenance therapy. The aim of our study was to evaluate the efficacy of exclusive zinc monotherapy in WD children with isolated hypertransaminasemia. Material and methods: All WD patients referred to our Department of Pediatrics for diagnostic investigation of elevated serum aminotransferases were analyzed. The diagnosis of WD was established in presence of at least two of the following features: a low ceruloplasmin level (<20 mg/dL), an increased basal urinary copper level (>100 mcg/24 hours), an increased urinary copper level after the penicillamine challenge test (PCT; >1575 mcg/24 hours), an increased liver copper level (>250 mcg/g of dry weight). Among43 enrolled WD patients,29 were treated with zinc for a median period of12 years (range 3-25). Zinc was the initial therapy of choice in12 cases. Normalization of serum ALT was the main parameter of treatment efficacy in this study. Compliance to therapy was evaluated on the basis of clinical history and serum and urine copper and zinc levels. Results: Among17 (58%) children, treated with penicillamine as first choice, 4 (24%) normalized ALT within a median of14 months (range,4 to48), and started maintenance therapy with zinc. The remaining13 (76%) patients with persistent hyper-ALT during penicillamine switched to zinc; nine of these (70%) normalized ALT on zinc within a median period of9.5 months (range, 5 to151). Eleven (92%) of the12 patients, given zinc alone as first-choice, normalized ALT within a median period of14 months (range,2 to46). The patient with persistent hyper-ALT on zinc showed a poor compliance to treatment. According to24 hour urinary copper excretion (56+4 versus 37+2 mcg) at the end of follow-up, the efficacy in terms of decopperization was comparable in two groups. Conclusions: Although penicillamine therapy is generally used for the initial treatment of Wilson disease, the present study has showed that zinc monotherapy may be used, as first line therapy, in WD children with isolated hypertransaminasemia at presentation.",gastrointestinal disease;therapy;human;child;liver disease;health care organization;patient;serum;diagnosis;Wilson disease;hypertransaminasemia;monotherapy;maintenance therapy;pediatrics;copper metabolism;follow up;urine;dry weight;liver;excretion;provocation test;diseases;zinc;penicillamine;copper;aminotransferase;ceruloplasmin,"Ranucci, G.;Di Dato, F.;Puoti, G.;Liccardo, D.;Tufano, M.;Iorio, R.",2012,March,http://dx.doi.org/10.1016/S1590-8658%2812%2960278-3,0,1,
1661,Concomitant immune mediated phenomenon in wilson disease: Implication for monitoring of chelator therapy,"Introduction: Wilson disease (WD) is a genetic copper storage disorder, leading to liver failure and neurological deterioration. Current guidelines favour the use of chelating agents (dpenicillamine, trientine) in first line therapy of symptomatic patients. Development of chelator induced immunological adverse events leading to impaired kidney function or bone marrow depression are a concern especially under d-pencillamine therapy. Based on few case reports, a predictive value for anti nuclear antibodies (ANA) in this context has been suggested. Aim: The current study aimed to assess the prevalence of coexisting or therapy related immune mediated disease in WD patients and to evaluate the role of anti nuclear antibodies in therapy monitoring in a retrospective cohort study. Patients and Methods: A total of 222 WD patients in an European tertiary care center were analysed retrospectively. Medical regimens were classified and analysed for adverse events and course of anti nuclear antibodies. Results: Hepatic and neuropsychiatric symptoms were present in 153/222 (69.0%) and in 71/222 (32.0%) patients, respectively. Confirmed coexisting immune mediated diseases were evident in 28/222 (12.6%) patients. Data on course of ANA under treatment and conclusive data on adverse events were available for 91 treatments with D-penicillamine, 58 treatments with trientine and 58 treatments with zinc salts. Within these treatments an increase of ANA titres were observed in 16/91 (17.6%) patients in the d-penicillamine group, in 12/58 (20.7%) patients in the trientine group and in 7/58 (12.1%) patients in the zinc group (p=n.s.). Analysis of adverse events leading to discontinuation of treatments showed no correlation to a preceding increase of ANA titres in all groups. Conclusion: In our cohort elevation of ANA was a frequent finding, but not related to disease presentation and independent from the applied medical regimen.We did not observe a correlation between an increase of ANA and the development of related immune mediated adverse events in all treatment groups and especially in the d-penicillamine group. Thus the value of this parameter for monitoring for adverse events seems to be clearly limited.",liver;Wilson disease;monitoring;therapy;human;patient;case report;prevalence;storage disease;predictive value;bone marrow depression;kidney function;diseases;tertiary health care;cohort analysis;deterioration;liver failure;chelating agent;penicillamine;antinuclear antibody;trientine;alprazolam;zinc derivative;zinc;copper,"Seesle, J.;Gotthardt, D. N.;Merle, U.;Gohdes, A.;Pfeiffenberger, J.;Stremmel, W.;Weiss, K. H.",2012,April,http://dx.doi.org/10.1016/S0168-8278%2812%2961405-6,0,1,
1662,Blisters from my surgery: Clinical history helped by internet pictures,"84 y/o WF admitted to a sub-acute rehab. to recover from complication from a total knee arthroplasty. PMHx. consists of DM, HTN, anemia, HLD, CAD, COPD, CKD, anxiety, and Hypothyroidism. After two weeks of successful rehabilitation, she developed blisters in her extremities and torso, with no other symptoms. When the blisters burst, they express a clear fluid, then crust and new blisters appear in other parts of her body. The patient was started on Prednisone while in the hospital but no documentation was found regarding the reason for it. With further interrogation, she stated that she had the blisters before and that steroids usually improved them. Until then, since no documentation found about her blisters, COPD exacerbations were the presumable cause for her steroid treatments. After reviewing and taking in consideration that the patient is a female older than 60, with previous episodes of non-complicated blistering, also that those blisters have responded to steroids treatment, and finally and foremost after comparing her lesions with the ones posted online in multiple sites Our patient was diagnosed with Bullous Pemphigoid and started on a long prednisone taper after which she improved and was successfully discharged home. Discussion: Bullous Pemphigoid is a fairly uncommon disease, but when present is usually in elderly females, it is one differential diagnosis we should think of when blisters are present in the elderly, followed by Pemphigus (similar but less common blistering disease). The difference between the two is auto antibodies to intradermal epitopes in the latter vs. sub dermal auto antibodies in the former. Both have been linked with higher risk of death, and this is why primary care geriatricians and anyone taking care of the elderly should be vigilant to diagnose and treat Bullous Pemphigoid, the treatment is mainly wound care (treat like a burn) and oral steroids. Recurrence is common and even longer steroid tapers might be required. Etiology is not well understood but an autoimmune response is known. The diagnosis is clinical. An association with some medications use is known (Furosemide, Penicillamine, and Captopril -among the most prominent-).",surgery;Internet;geriatrics;society;blister;human;bullous pemphigoid;aged;patient;female;documentation;rehabilitation;total knee replacement;hypothyroidism;hospital;diagnosis;wound care;primary medical care;risk;anxiety;death;pemphigus;etiology;differential diagnosis;drug therapy;anemia;liquid;trunk;steroid;autoantibody;prednisone;penicillamine;furosemide;captopril;epitope,"Garrido, A. I.;Chakka, A.;Iloabuchi, T.;Perez, F.;Nazir, A.",2012,April,http://dx.doi.org/10.1111/j.1532-5415.2012.04000.x,0,0,
1663,"Copper deficiency myeloneuropathy with hypozincemia due to zinc excess, gastrectomy, and low serum ceruloplasmin","Objective: We describe low serum zinc level in copper deficiency myeloneuropathy (CuDM) associated with excess zinc ingestion and prior gastrectomy. Background The malabsorption of copper occurs after gastrectomy or bariatric surgeries and can cause CuDM. The antagonistic relationship between copper and zinc is the basis for treatment of states of copper excess (e.g. Wilson's disease) with zinc supplementation. Zinc excess due to long term denture cream usage can be the cause of CuDM. Design/Methods: Case Report: An 83 year old man developed progressive triple flexor spasms, severe sensory loss, and absent/diminished reflexes with Babinski signs over 5 years following gastrectomy 38 years previously, using zinc-based denture cream (three tubes weekly) for 30 years, and having hypoceruloplasminemia. Serum copper was 0.12 mug/mL (RI 0.75-1.45mcg/mL), ceruloplasmin 4.0 mg/dL (RI 15-30mg/dL), and serum zinc 0.58 mug/mL (RI 0.66-1.0mcg/mL). Results: Our patient had three causes for CuDM-hypocupremia, excess intake of zinc, and hypoceruloplasminemia. Patients with CuDM due to excess zinc ingestion may have normal to elevated serum zinc levels (Nations 2008). Hypozincemia was noted by Kumar, et al (Kumar 2004) in a patient following gastrectomy and poor copper absorption. Gastrectomy will, in addition to decreasing serum copper levels, also decrease serum zinc. Our patient demonstrated low serum zinc levels in the face of excess zinc ingestion and was likely the result of his prior gastrectomy. Conclusions: Excess ingestion of zinc interferes with the absorption of copper and can result in CuDM. Our patient with CuDM, related to prior gastrectomy, excess zinc ingestion, and hypoceruloplasminemia, had a low serum zinc level. This likely reflected decreased zinc absorption due to his prior gastrectomy. Low serum zinc does not exclude CuDM.",gastrectomy;ceruloplasmin blood level;neurology;copper deficiency;zinc blood level;human;patient;ingestion;absorption;copper blood level;case report;denture;supplementation;tube;bariatric surgery;malabsorption;Babinski reflex;reflex;infantile spasm;male;Wilson disease;zinc;copper;ceruloplasmin,"Josiah, A.;Salomon, A.;Tacker, D.;Gutmann, L.",2012,,http://dx.doi.org/10.1212/WNL.78.1,0,0,
1664,Certain issues and our suggestions in the pharmaceutical treatment of wilson disease,"Wilson disease (WD) is an autosomal recessive disorder of excessivecopper accumulation in the body. It is a very rare condition inCaucasian populations, but seems to be more common in Chinese. Here we summarized our experience in the pharmatheuticaltreatment of the disease: (1) we select different initial treatmentmedications for patients with different presentations. In general, wechoose penicillamine for patients with mainly hepatic symptoms.Penicillamine should be avoided, or used with great caution,in patients with significant rigidity, drooling, dysarthria anddysphagia. (2) treatment of WD should be initiated as early aspossible. Zinc agents alone may be sufficient for asymptomaticWD children with only abnormal liver function tests. Penicillamineshould be added once they become symptomatic or have abnormalliver sonogram. (3) 24 hour urine copper content is a good referencefor the adjustment of medication doses. A target of 200-500 ug of24 UCC is usually an indicator of good chelating dosing. (4) lifelongtreatment with good compliance should be emphasized. (5) zinccan be used during the pregnancy. Small dose of penicillamine(250 mg/d) may be added if necessary. (6) Chinese herbal medicinesshould be careful selected and be used as adjunct treatment.",Wilson disease;Parkinson disease;human;female;patient;child;liver function test;echography;pregnancy;autosomal recessive disorder;population;rigidity;drug therapy;hypersalivation;dysarthria;urine;penicillamine;copper;zinc,"Liang, X. L.;Li, X. H.;Chen, R.",2012,January,http://dx.doi.org/10.1016/S1353-8020%2811%2970733-7,0,0,
1665,Wilson's disease in the south of Brazil: A 40 years follow-up study,"Introduction: Wilson's disease (WD) is an autosomal recessive inherited disorder of the copper metabolism leading to the accumulation of this metal in different organs and tissues. Hepatic and neurological symptoms are the main clinical features of the disease. Objective: The aim of study is to analyze the clinical presentation, epidemiological features, the disease course and the response to therapy in a historical cohort of 36 Brazilian WD patients. Patients and Methods: 36 patients with WD, diagnosed from 1971 to 2010, and followed in the south of Brazil were reviewed. Diagnosis of WD was based on clinical presentation, familial history, Kayser-Fleischer rings, low serum cerulosplasmin, increased 24 h urinary copper excretion, liver biopsy, genetic test and/or response to a D-penicillamine provocative test. Results: There were 16 (44.4%) male and 20 female (56.6%) patients, with mean age of 34.6+/-10.8 years, with high predominance of an exclusively European continental origin (74.5%). Mean age at the initial symptom presentation was 23.2+/-9.3 years. The time since the first clinical symptom and the definitive diagnosis was of 27.5+/-41.9 months. At presentation, 9 patients (25%) showed exclusively neuropsychiatric symptoms, 14 (38.9%) exclusively hepatic symptoms, 11 (30.6%) demonstrated both hepatic and neuropsychiatric features (mixed presentation) and 2 (5.5%) were asymptomatic. Treatment used included D-penicillamine (94.2%) and zinc acetate (5.8%). Conclusion: Our cohort of WD patients has the European continental origin as a unique characteristic, which differs from previous series described in Brazil. The follow-up and response to treatment was similiar to previous studies.",Wilson disease;Brazil;follow up;Parkinson disease;human;patient;diagnosis;clinical feature;disease course;therapy;female;excretion;male;serum;autosomal recessive inheritance;copper metabolism;tissue;neurologic disease;liver biopsy;penicillamine;copper;zinc acetate;metal,"Teive, H. A. G.;De Bem, R. S.;Muzillo, D.;Deguti, M. M.;Munhoz, R. P.;Barbosa, E. R.",2012,January,http://dx.doi.org/10.1016/S1353-8020%2811%2970335-2,0,1,
1666,An overview of biochemical genetics,"Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of inherited metabolic disorders. While individually rare, the combined incidence of these diseases is likely greater than 1:3000 live births. These conditions may present in the neonatal period as an acute, life-threatening illness, or may manifest later in childhood with symptoms of progressive neurodegeneration, skeletal abnormalities, and/or dysmorphia. The purpose of this introductory unit is to provide an overview of the different clinical categories of metabolic disorders, modern diagnostic methods, and treatment options. © 2011 by John Wiley & Sons, Inc.",Biochemical;Enzyme;Enzyme-replacement therapy;Genetics;Mass spectrometry;Metabolism;adrenoleukodystrophy/di [Diagnosis];adrenoleukodystrophy/dt [Drug Therapy];adrenoleukodystrophy/th [Therapy];apheresis;argininosuccinic aciduria/di [Diagnosis];argininosuccinic aciduria/dt [Drug Therapy];argininosuccinic aciduria/th [Therapy];article;bone malformation;bone marrow transplantation;carbamoyl phosphate synthetase I deficiency/di [Diagnosis];carbamoyl phosphate synthetase I deficiency/dt [Drug Therapy];carbamoyl phosphate synthetase I deficiency/th [Therapy];carnitine palmitoyltransferase deficiency type 1/di [Diagnosis];carnitine palmitoyltransferase deficiency type 1/th [Therapy];chelation therapy;clinical feature;congenital disorder of glycosylation type 1a/cn [Congenital Disorder];congenital disorder of glycosylation type 1a/di [Diagnosis];congenital disorder of glycosylation type 1b/cn [Congenital Disorder];congenital disorder of glycosylation type 1b/di [Diagnosis];creatine transporter deficiency/di [Diagnosis];diet restriction;diet therapy;enzyme replacement;familial hypercholesterolemia/di [Diagnosis];familial hypercholesterolemia/dt [Drug Therapy];familial hypercholesterolemia/su [Surgery];familial hypercholesterolemia/th [Therapy];galactosemia/di [Diagnosis];galactosemia/th [Therapy];Gaucher disease/di [Diagnosis];Gaucher disease/th [Therapy];gene mutation;glycogen storage disease type 1/di [Diagnosis];glycogen storage disease type 1/th [Therapy];guanidinoacetate methyltransferase deficiency/dt [Drug Therapy];guanidinoacetate methyltransferase deficiency/di [Diagnosis];hemochromatosis/di [Diagnosis];hemochromatosis/th [Therapy];hereditary fructose intolerance/di [Diagnosis];hereditary fructose intolerance/th [Therapy];human;Hurler Scheie disease/di [Diagnosis];Hurler Scheie disease/th [Therapy];hyperglycinemia;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/ep [Epidemiology];inborn error of metabolism/th [Therapy];incidence;isovaleric acidemia/di [Diagnosis];isovaleric acidemia/dt [Drug Therapy];isovaleric acidemia/th [Therapy];laboratory diagnosis;Leber hereditary optic neuropathy/di [Diagnosis];Leber hereditary optic neuropathy/dt [Drug Therapy];Lesch Nyhan syndrome/di [Diagnosis];Lesch Nyhan syndrome/dt [Drug Therapy];lifestyle modification;liver transplantation;maple syrup urine disease/di [Diagnosis];maple syrup urine disease/dt [Drug Therapy];maple syrup urine disease/th [Therapy];medium chain acyl coenzyme A dehydrogenase deficiency/di [Diagnosis];medium chain acyl coenzyme A dehydrogenase deficiency/dt [Drug Therapy];medium chain acyl coenzyme A dehydrogenase deficiency/th [Therapy];MELAS syndrome/di [Diagnosis];MELAS syndrome/dt [Drug Therapy];Menkes syndrome/di [Diagnosis];Menkes syndrome/dt [Drug Therapy];methylmalonic acidemia/di [Diagnosis];methylmalonic acidemia/dt [Drug Therapy];methylmalonic acidemia/th [Therapy];molecular genetics;nerve degeneration;newborn screening;ornithine transcarbamylase deficiency/di [Diagnosis];ornithine transcarbamylase deficiency/dt [Drug Therapy];ornithine transcarbamylase deficiency/th [Therapy];orotic aciduria type 1/dt [Drug Therapy];orotic aciduria type 1/di [Diagnosis];phenylketonuria/di [Diagnosis];phenylketonuria/dt [Drug Therapy];phenylketonuria/ep [Epidemiology];phenylketonuria/th [Therapy];plasmapheresis;priority journal;propionic acidemia/di [Diagnosis];propionic acidemia/dt [Drug Therapy];propionic acidemia/th [Therapy];protein restriction;pyruvate dehydrogenase complex deficiency/di [Diagnosis];pyruvate dehydrogenase complex deficiency/dt [Drug Therapy];qualitative analysis;quantitative analysis;Refsum disease/di [Diagnosis];Refsum disease/th [Therapy];Smith Lemli Opitz syndrome/di [Diagnosis];Smith Lemli Opitz syndrome/dt [Drug Therapy];supplementation;tandem mass spectrometry;Tay Sachs disease/di [Diagnosis];tyrosinemia/di [Diagnosis];tyrosinemia/dt [Drug Therapy];tyrosinemia/su [Surgery];tyrosinemia/th [Therapy];urea cycle disorder/dt [Drug Therapy];very long chain acyl coenzyme A dehydrogenase deficiency/dt [Drug Therapy];very long chain acyl coenzyme A dehydrogenase deficiency/di [Diagnosis];very long chain acyl coenzyme A dehydrogenase deficiency/th [Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Zellweger syndrome/di [Diagnosis];allopurinol/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];arginine/dt [Drug Therapy];ascorbic acid/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];biotin/dt [Drug Therapy];carnitine/dt [Drug Therapy];cholesterol/dt [Drug Therapy];citrulline/dt [Drug Therapy];copper/dt [Drug Therapy];copper/sc [Subcutaneous Drug Administration];creatine/dt [Drug Therapy];glycine/dt [Drug Therapy];hydroxocobalamin/dt [Drug Therapy];hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy];Lorenzo oil/dt [Drug Therapy];nicotinic acid/dt [Drug Therapy];nitisinone/dt [Drug Therapy];ornithine/dt [Drug Therapy];phenylacetic acid/dt [Drug Therapy];riboflavin/dt [Drug Therapy];simvastatin/dt [Drug Therapy];steroid/dt [Drug Therapy];tetrahydrobiopterin/dt [Drug Therapy];thiamine/dt [Drug Therapy];thioctic acid/dt [Drug Therapy];ubiquinone/dt [Drug Therapy];unindexed drug;uridine/dt [Drug Therapy];vitamin K group/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Sharer, J. D.",2011,July,http://dx.doi.org/10.1002/0471142905.hg1701s70,0,0,
1667,Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort,"Wide phenotypic and genotypic heterogeneities in Wilson's disease (WD) have been reported, hampering the study of their correlations. The goal of this study was to identify the factors related to these diversities. Methods: Clinical courses and molecular genetic characteristics were analysed in 237 unrelated Korean WD families. The average follow-up period was 8.2 +/- 5.8 years. Results: Presenting phenotypes were classified as H1 (12.2%), H2 (42.4%), N1 (21.6%), N2 (0.4%), NX (0.4%), presymptomatic (22.4%) and other (0.4%), modifying the guidelines by Ferenci and colleagues. Age at presentation was youngest and cirrhosis was rarest in the presymptomatic group. Decompensated cirrhosis was the highest in the H1 group. Favourable outcome was rarest in the N1 group. Forty-seven (11 novel) ATP7B mutations were identified in 85% of the 474 alleles. Multiplex ligation-dependent probe amplification assays in ATP7B and analyses of ATOX1 and COMMD1 genes identified no additional mutations. Yeast complementation assays demonstrated functional perturbation of the seven novel missense mutants. Five major mutations, p.Arg778Leu, p.Ala874Val, p.Asn1270Ser, p.Lys838SerfsX35 and p.Leu1083Phe, accounted for 63% of the alleles. H1 was more common, age at presentation was younger and N1+N2+NX tended to be less common in patients with nonsense, frame shifting or splicing mutations than in those with missense mutations alone. Patients with both mutations in the transduction (Td) or the ATP hinge domain showed presymptomatic or hepatic manifestations but no neurological manifestation. Conclusions: The presenting phenotype strongly affects the clinical outcome of WD, and is related to the ATP7B mutation type and location, providing an evidence for genotype-phenotype correlations in WD. © 2011 John Wiley & Sons A/S.",atp7b;Domain;Genotype;Mutation;Phenotype;Wilson's disease;acute liver failure;adolescent;adult;amino acid substitution;arthralgia;article;ceruloplasmin blood level;child;cohort analysis;controlled study;disease course;drug substitution;drug withdrawal;follow up;frameshift mutation;gene deletion;gene frequency;gene identification;gene insertion;gene mutation;genetic transduction;genetic variability;genotype phenotype correlation;hinge region;human;human cell;infant;liver cirrhosis;liver disease;major clinical study;missense mutation;molecular genetics;multiplex ligation dependent probe amplification;mutational analysis;neurologic disease;nonsense mutation;nucleotide sequence;onset age;outcome assessment;patient compliance;phylogeny;preschool child;RNA splicing;school child;unspecified side effect/si [Side Effect];urinary excretion;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alanine/ec [Endogenous Compound];arginine/ec [Endogenous Compound];asparagine/ec [Endogenous Compound];Atox1 protein/ec [Endogenous Compound];carrier protein/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chaperone/ec [Endogenous Compound];COMMD1 protein/ec [Endogenous Compound];copper/ec [Endogenous Compound];leucine/ec [Endogenous Compound];lysine/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];phenylalanine/ec [Endogenous Compound];serine/ec [Endogenous Compound];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];unclassified drug;valine/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy],"Lee, B. H.;Kim, J. H.;Lee, S. Y.;Jin, H. Y.;Kim, K. J.;Lee, J. J.;Park, J. Y.;Kim, G. H.;Choi, J. H.;Kim, K. M.;Yoo, H. W.",2011,July,http://dx.doi.org/10.1111/j.1478-3231.2011.02503.x,0,0,
1668,A primer on Wilson disease for the general practitioner. [French],"Wilson disease (WD) is an inherited disorder of hepatic copper excretion leading to toxic accumulation of copper in the liver as well as the brain, cornea, and other organs. The defect is due to mutations of the copper-transporting ATPase ATP7B. Clinical manifestations are highly variable and comprise acute liver failure, chronic hepatitis and cirrhosis as well as neurological or psychiatric symptoms. The Kayser-Fleischer corneal ring is pathognomonic but absent in about 50% of patients with hepatic manifestations alone. A high index of suspicion in clinically compatible situations is key, with a combination of laboratory tests allowing the diagnosis of WD. Treatment is based on the use of chelating agents, D-penicillamine or trientine. Liver transplantation should be considered for patients with acute liver failure or advanced cirrhosis.",acute liver failure/su [Surgery];brain level;chronic hepatitis;clinical feature;copper metabolism;cornea;gene mutation;general practitioner;human;laboratory test;liver cirrhosis/th [Therapy];liver level;liver toxicity;liver transplantation;mental disease;neurologic disease;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];copper/to [Drug Toxicity];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Hiroz, P.;Antonino, A.;Doerig, C.;Pache, I.;Moradpour, D.",2011,07 Sep,,0,0,
1669,Values of serum copper and serum free copper in the diagnosis and monitoring of Wilson's disease and its carriers. [Chinese],"Objective: To explore the values of serum copper and serum free copper in the diagnosis of Wilson's disease (WD), its carrier and viral hepatitis and explore the guiding significance of monitoring serum copper in the treatment of WD. Methods: A total of 80 WD patients (hepatic type, n=60; encephalic type, n=20), 30 carriers, 20 patients with viral hepatitis were enrolled and their levels of serum copper were determined. The neural symptoms were scored by modified Young grade. Hemogram, hepatic functions, blood clotting functions, serum copper and urinary copper were tested throughout all 8 courses of treatment with sodium dimercaptopropane sulfonate (DMPS). The patients were treated with zinc after discharging. All data were analyzed. Results: The free serum copper increased in the patients with WD (0.17 mg/L +/- 0.04 mg/L), carriers (0.13 mg/L +/- 0.03 mg/L) and severe viral hepatitis (0.12 mg/L). A slight increase was also observed in the WD carriers. The level of serum copper was correlated with hepatic functions but not with the severity of neural symptoms. The serum copper increased in the patients with no improvement of neural symptoms. However, the serum copper decreased in the WD patients with the improvement of neural symptoms. The serum copper was stabilized at approximately 0.2 mg/L during the long-term treatment period. Conclusion: There is auxiliary diagnosis significance of serum copper in the determination of WD. Hepatic functions in hepatic type WD affect the level of serum copper. The serum copper of encephalic type WD can not indicate the severity of neural symptoms. The elevated level of serum copper indicates a poor prognosis. The serum copper is an effective marker in monitoring the development and therapeutic efficacy of the disease. Copyright © 2011 by the Chinese Medical Association.",Serum copper;Sodium dimercaptopropane sulfonate;Wilson's disease;Zinc;article;blood clotting;copper blood level;disease marker;disease severity;hospital discharge;human;liver function;major clinical study;patient monitoring;prognosis;virus hepatitis;Wilson disease/di [Diagnosis];copper/ec [Endogenous Compound];unithiol,"Zhou, X. X.;Li, X. H.;Huang, H. W.;Liu, B.;Zhu, R. L.;Liang, Y. Y.;Zhu, J. Z.;Liang, X. L.",2011,25 Oct,http://dx.doi.org/10.3760/cma.j.issn.0376-2491.2011.39.007,0,0,
1670,Ulcerative colitis and primary sclerosing cholangitis. The long way to diagnosis. [German],"We are reporting on the case of a 13-year-old boy, who was free of any symptoms, but showed elevated transaminases and gamma-GT in a routine blood examination. The extremely increased hepatic copper concentration resulted in the diagnosis of Wilson's disease; a therapy with D-penicillamine was initiated. A few weeks later the boy presented with weight loss and signs of colitis and pancreatitis. Interruption of therapy resulted in improvement of the colitis. After recurrence of symptoms during re-exposure, the penicillamine therapy was stopped because of suspected drug-induced colitis and pancreatitis. Under an alternative zinc therapy the liver enzymes again increased, accompanied by an elevation of auto-antibodies and persistently high fecal lacto-ferrin. The following reevaluation led to the final diagnosis of primary sclerosing cholangitis (PSC) and ulcerative colitis. The above case demonstrates the diagnostic difficulties in cases of increased transaminases without specific clinical symptoms. Despite the high specificity of liver copper content for diagnosis of Wilson's disease, any cholestatic liver diseases have to be excluded, as they may lead to a distinct secondary hepatic copper storage. Based on the reported case, the characteristics of ulcerative colitis and PSC are presented, in particular their association, diagnostics and therapy.",Cholestasis;Primary sclerosing cholangitis;Ulcerative colitis;Wilson's disease;adolescent;aminotransferase blood level;article;case report;clinical feature;colitis/si [Side Effect];disease course;drug withdrawal;human;liver level;male;pancreatitis/si [Side Effect];primary sclerosing cholangitis/di [Diagnosis];ulcerative colitis/di [Diagnosis];weight reduction;Wilson disease/dt [Drug Therapy];aminotransferase;copper;gamma glutamyltransferase;lactoferrin;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc,"Tesch, N.;Lange, L.;Vorndamme, I.;Buderus, S.",2011,December,,0,0,
1671,Musculoskeletal conditions associated with Wilson's disease,"Wilson's disease (WD) is a rare disease, defined as an autosomal recessive disorder characterised by release of free copper and dramatic accumulation of intracellular hepatic copper with subsequent hepatic and central nervous system abnormalities. Mutations of the ATP7B gene are responsible for the metabolic dysfunction. Small open studies have reported spinal radiological abnormalities including scoliosis, diffuse bone demineralisation, osteochondritis and occasionally fracture. Prevalence of osteoporosis in young adult patients is debated, ranging from 10%, with normal mean Z-score values, to 43% in adults. Past history of spinal or peripheral fractures might be present in 50% of patients. Articular disorders include arthralgias of large joints, such as knee pain, rare effusions, early onset of radiological features of osteoarthritis and associated osteochondritis of the knee joint. Radiological chondrocalcinosis, an unusual feature in young adults, has to be confirmed. Few patients may develop drug-induced lupus with arthralgias, positive anti-nuclear and anti-histone antibodies, secondary to D-penicillamine, the major copper chelator used in WD. In this orphan disease, small retrospective studies cannot allow ascertaining definite WD-related articular and bone manifestations. However, such clinical and radiological abnormalities are occasionally the first symptoms leading to diagnosis. Physicians should be aware that unexplained joint pain and effusion, or even radiological features of osteoarthritis, of the large joints in adolescents could suggest WD and lead to copper survey. © 2011 Elsevier Ltd. All rights reserved.",Arthralgia;Bone mineral density;Chondrocalcinosis;Fracture;Osteoarthritis;Osteoporosis;Wilson's disease;article;autosomal recessive disorder;bone demineralization;bone density;clinical feature;copper metabolism;dermatomyositis/si [Side Effect];diagnostic imaging;diet therapy;disease association;drug mechanism;gene mutation;Goodpasture syndrome/si [Side Effect];human;joint effusion;knee pain;liver transplantation;lupus like syndrome/si [Side Effect];musculoskeletal disease;myasthenia/si [Side Effect];nuclear magnetic resonance imaging;osteochondritis;pathophysiology;priority journal;rare disease;scoliosis;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];antinuclear antibody;ceruloplasmin;histone antibody;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];Wilson disease protein;zinc acetate/dt [Drug Therapy];zinc acetate/pd [Pharmacology],"Quemeneur, A. S.;Trocello, J. M.;Ea, H. K.;Woimant, F.;Liote, F.",2011,October,http://dx.doi.org/10.1016/j.berh.2011.10.021,0,0,
1672,Wilson's disease in southern Brazil: A 40-year follow-up study,"BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5% had a European ancestor. The mean age at the initial symptom presentation was 23.3 +/- 9.3 years, with a delay of 27.5 +/- 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9%), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6%) and neuropsychiatric symptoms (25%). Kayser-Fleischer rings were identified in 55.6% of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8%). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2% of these patients. Chronic liver disease was detected in 68% of the patients with hepatic symptoms. 94.2% of all the patients were treated with D-penicillamine for a mean time of 129.9 +/- 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8% of the patients had a stable or improved outcome, and the overall survival rate was 90.1%. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival. © 2011 CLINICS.",Genetic and inherited disorders;Medication;Outcome;Treatment;Wilson's disease;adolescent;adult;age;age distribution;article;Brazil/ep [Epidemiology];child;ethnology;female;follow up;human;liver;male;middle aged;pathology;retrospective study;sex ratio;survival rate;time;treatment outcome;Wilson disease/ep [Epidemiology];Wilson disease/th [Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"de Bem, R. S.;Muzzillo, D. A.;Deguti, M. M.;Barbosa, E. R.;Werneck, L. C.;Teive, H. A. G.",2011,,http://dx.doi.org/10.1590/S1807-59322011000300008,0,1,
1673,Quality of life in patients with treated and clinically stable Wilson's disease,"Health-related quality of life (HRQoL) in Wilson's disease (WD) has not been extensively studied. Therefore, the purpose of this cross-sectional study was to identify clinical and demographic factors influencing HRQoL in 60 treated, clinically stable patients with WD using a generic questionnaire, the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36). The level of disability and grading of WD multisystemic manifestations were assessed by the Global Assessment Scale for WD (GAS for WD). The Mini Mental State Examination (MMSE) and the 21-item Hamilton Depression Rating Scale (HDRS) scoring were also applied by the same trained interviewers. Lower scores on the SF-36 domains were found in patients with neurological compared with those with a predominantly hepatic form of WD. The HRQoL of patients with WD and psychiatric symptoms was also lower than that of those without them. Finally, significant inverse correlations were obtained between the various SF-36 domains and all the following: period of latency from the first symptoms/signs appearance and treatment initiation, MMSE and HDRS scores, and different domains of the GAS for WD. © 2011 Movement Disorder Society.",Quality of life;Wilson disease;adult;article;clinical feature;cross-sectional study;demography;female;Global Assessment Scale;Hamilton Anxiety Scale;health survey;human;interview;major clinical study;male;mental disease;Mini Mental State Examination;priority journal;questionnaire;Short Form 36;Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Svetel, M.;Pekmezovic, T.;Tomic, A.;Kresojevic, N.;Potrebic, A.;Jesic, R.;Kostic, V. S.",2011,July,http://dx.doi.org/10.1002/mds.23608,0,0,
1674,"Medical management of chronic liver diseases (CLD) in children (part II): Focus on the complications of CLD, and CLD that require special considerations","Treatment of the causes of many chronic liver diseases (CLDs) may not be possible. In this case, complications must be anticipated, prevented or at least controlled by the best available therapeutic modalities. There are three main goals for the management of portal hypertension: (i) prevention of the first episode of variceal bleeding largely by non-selective beta-adrenoceptor antagonists, which is not generally recommended in children; (ii) control of bleeding by using a stepwise approach from the least to most invasive strategies; (iii) and prevention of re-bleeding using bypass operations, with particular enthusiasm for the use of meso-Rex bypass in the pediatric population. Hepatic encephalopathy management also consists of three main aspects: (i) ruling out other causes of encephalopathy; (ii) identifying and treating precipitating factors; and (iii) starting empiric treatment with drugs such as lactulose, rifaximin, sodium benzoate, and flumazenil. Treatment of mild ascites and peripheral edema should begin with the restriction of sodium and water, followed by careful diuresis, then large-volume paracentesis associated with colloid volume expansion in severe cases. Empiric broad spectrum antimicrobial therapy should be used for the treatment of spontaneous bacterial peritonitis, bacterial and fungal sepsis, and cholangitis, after taking appropriate cultures, with appropriate changes in therapy after sensitivity testing. Empirical therapies continue to be the standard practice for pruritus; these consist of bile acid binding agents, phenobarbital (phenobarbitone), ursodeoxycholic acid, antihistamines, rifampin (rifampicin), and carbamazepine. Partial external biliary diversion can be used in refractory cases. Once hepatorenal syndrome is suspected, treatment should be initiated early in order to prevent the progression of renal failure; approaches consist of general supportive measures, management of concomitant complications, screening for sepsis, treatment with antibiotics, use of vasopressin analogs (terlipressin), and renal replacement therapy if needed. Hepatopulmonary syndrome and portopulmonary hypertension are best managed by liver transplantation. Provision of an adequate caloric supply, nutrition, and vitaminmineral supplements for the management of growth failure, required vaccinations, and special care for ensuring psychologic well-being should be ensured. Anticoagulation might be attempted in acute portal vein thrombosis.Some CLDs, such as extrahepatic biliary atresia (EHBA), Crigler-Najjar syndrome, and Indian childhood cirrhosis, require special considerations. For EHBA, Kasai hepatoportoenterostomy is the current standard surgical approach in combination with nutritional therapy and supplemental fat and water soluble vitamins, minerals, and trace elements. In type 1 Crigler-Najjar syndrome, extensive phototherapy is the mainstay of treatment, in association with adjuvant therapy to bind photobilirubin such as calcium phosphate, cholestyramine, or agar, until liver transplantation can be carried out. Treating Indian childhood cirrhosis with penicillamine early in the course of the disease and at doses similar to those used to treat Wilson disease decreases the mortality rate by half.New hopes for the future include extracorporeal liver support devices (the molecular adsorbent recirculating system MARS and Prometheus), hepatocyte transplantation, liver-directed gene therapy, genetically engineered enzymes, and therapeutic modalities targeting fibrogenesis. Hepapoietin, a naturally occurring cytokine that promotes hepatocyte growth, is under extensive research. © 2011 Adis Data Information BV. All rights reserved.",albumin dialysis;antibiotic therapy;anticoagulation;ascites/di [Diagnosis];ascites/et [Etiology];ascites/th [Therapy];bacterial peritonitis/dt [Drug Therapy];bile duct atresia;bleeding/co [Complication];bleeding/pc [Prevention];bypass surgery;cholangitis/dt [Drug Therapy];cholestasis;chronic liver disease/di [Diagnosis];chronic liver disease/et [Etiology];chronic liver disease/th [Therapy];continuous infusion;Crigler Najjar syndrome/th [Therapy];diuresis;emotion;growth disorder;hepatic encephalopathy/dt [Drug Therapy];hepatopulmonary syndrome;hepatorenal syndrome/dt [Drug Therapy];human;Indian childhood cirrhosis/dt [Drug Therapy];Indian childhood cirrhosis/et [Etiology];Indian childhood cirrhosis/th [Therapy];liver transplantation;mycosis/dt [Drug Therapy];paracentesis;peripheral edema;phototherapy;portal hypertension/dt [Drug Therapy];portal vein obstruction;portopulmonary hypertension;priority journal;pruritus/dt [Drug Therapy];review;sepsis/dt [Drug Therapy];surgical technique;varicosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];antibiotic agent/dt [Drug Therapy];antifungal agent/dt [Drug Therapy];antihistaminic agent/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];calcium phosphate;carbamazepine/dt [Drug Therapy];colestipol;colestyramine;diphenhydramine;flumazenil/dt [Drug Therapy];hydroxyzine;lactulose/dt [Drug Therapy];octreotide/dt [Drug Therapy];octreotide/pd [Pharmacology];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];rifampicin/dt [Drug Therapy];rifaximin/dt [Drug Therapy];somatostatin derivative/dt [Drug Therapy];somatostatin derivative/pd [Pharmacology];terlipressin/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];vasopressin/pd [Pharmacology];vasopressin derivative/dt [Drug Therapy],"El-Shabrawi, M. H. F.;Kamal, N. M.",2011,,http://dx.doi.org/10.2165/11591620-000000000-00000,0,0,
1675,Medical management of chronic liver diseases in children (Part I): Focus on curable or potentially curable diseases,"The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation.Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs.Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone 2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-alpha-2, pegylated IFN-alpha-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin alpha-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic strategy for inducing remission in autoimmune hepatitis. Ciclosporin (cyclosporine) and other immune suppressants may be used for patients who do not achieve remission, or who have significant side effects, with corticosteroidazathioprine therapy.The above therapies can prevent, or at least minimize, progression of liver damage, particularly if started early, leading to an almost normal quality of life in affected children. © 2011 Adis Data Information BV. All rights reserved.",alopecia/si [Side Effect];aminotransferase blood level;anemia/si [Side Effect];anorexia/si [Side Effect];arthralgia/si [Side Effect];autoimmune disease/si [Side Effect];autoimmune hepatitis/dt [Drug Therapy];bone marrow suppression/si [Side Effect];chronic liver disease/di [Diagnosis];chronic liver disease/dm [Disease Management];chronic liver disease/et [Etiology];chronic liver disease/th [Therapy];depression/si [Side Effect];dietary intake;drug efficacy;early diagnosis;eosinophilia/si [Side Effect];fatigue/si [Side Effect];fatty liver/si [Side Effect];fever/si [Side Effect];flu like syndrome/si [Side Effect];galactosemia/th [Therapy];gastritis/si [Side Effect];gastrointestinal symptom/si [Side Effect];glycogen storage disease/th [Therapy];Goodpasture syndrome/si [Side Effect];growth retardation/si [Side Effect];hair loss/si [Side Effect];headache/si [Side Effect];hearing loss/si [Side Effect];hepatitis/si [Side Effect];hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];hepatomegaly/si [Side Effect];hereditary fructose intolerance/th [Therapy];human;hypersensitivity reaction/si [Side Effect];hypertriglyceridemia/si [Side Effect];immunopathogenesis;insomnia/si [Side Effect];iron deficiency anemia/si [Side Effect];irritability;lactic acidosis/si [Side Effect];leukopenia/si [Side Effect];liver toxicity/si [Side Effect];liver transplantation;nausea/si [Side Effect];nephrotic syndrome/si [Side Effect];neutropenia/si [Side Effect];nonalcoholic fatty liver/th [Therapy];optic neuritis/si [Side Effect];pancreatitis/si [Side Effect];peripheral neuropathy/si [Side Effect];polymyositis/si [Side Effect];priority journal;quality of life;rash/si [Side Effect];review;side effect/si [Side Effect];stomatitis/si [Side Effect];suicidal behavior/si [Side Effect];systemic lupus erythematosus/si [Side Effect];taste aversion;thrombocytopenia/si [Side Effect];tinnitus/si [Side Effect];tyrosinemia/dt [Drug Therapy];tyrosinemia/th [Therapy];vertigo/si [Side Effect];vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];adefovir/dt [Drug Therapy];alpha interferon/ae [Adverse Drug Reaction];alpha interferon/sc [Subcutaneous Drug Administration];alpha2 interferon/ae [Adverse Drug Reaction];alpha2 interferon/dt [Drug Therapy];alpha2 interferon/po [Oral Drug Administration];antioxidant/dt [Drug Therapy];antivirus agent/po [Oral Drug Administration];azathioprine/ae [Adverse Drug Reaction];azathioprine/ad [Drug Administration];azathioprine/dt [Drug Therapy];azathioprine/iv [Intravenous Drug Administration];azathioprine/po [Oral Drug Administration];corticosteroid/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];entecavir/dt [Drug Therapy];lamivudine/ae [Adverse Drug Reaction];lamivudine/dt [Drug Therapy];lamivudine/po [Oral Drug Administration];lamivudine/pd [Pharmacology];nitisinone/dt [Drug Therapy];peginterferon/ae [Adverse Drug Reaction];peginterferon/cb [Drug Combination];peginterferon/dt [Drug Therapy];peginterferon/sc [Subcutaneous Drug Administration];peginterferon alpha2a/dt [Drug Therapy];peginterferon alpha2a/po [Oral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology];ribavirin/ae [Adverse Drug Reaction];ribavirin/ad [Drug Administration];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];ribavirin/po [Oral Drug Administration];ribavirin/sc [Subcutaneous Drug Administration];tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"El-Shabrawi, M. H. F.;Kamal, N. M.",2011,,http://dx.doi.org/10.2165/11591610-000000000-00000,0,0,
1676,Renal tubular acidosis due to Wilson's disease presenting as metabolic bone disease,"Two sisters presented with lower limb deformity and diffi culty in walking without support. Both had short stature; however, neurodevelopment and secondary sexual characters were normal. Abdominal examination revealed splenomegaly and ophthalmic examination showed presence of Kayser-Fleischer (K-F) rings. Diagnosis of Wilson's disease was confi rmed with low serum copper and ceruloplasmin levels. Further investigations revealed urinary acidifi cation defect with hypercalciuria pointing towards distal renal tubular acidosis. Both patients were started on copper chelation therapy and showed gradual radiographic improvement in osteopaenia. Copyright 2011 BMJ Publishing Group. All rights reserved.",adolescent;article;bone radiography;case report;ceruloplasmin blood level;copper blood level;drug dose increase;female;human;hypercalciuria;kidney tubule acidosis/di [Diagnosis];kidney tubule acidosis/dt [Drug Therapy];kidney tubule acidosis/et [Etiology];leg malformation;metabolic bone disease/et [Etiology];nerve cell differentiation;osteopenia/di [Diagnosis];osteopenia/et [Etiology];physical examination;priority journal;sexual development;short stature;sibling;splenomegaly;urine acidification;visual system examination;walking difficulty;Wilson disease;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];zinc,"Palkar, A. V.;Shrivastava, M. S.;Padwal, N. J.;Padhiyar, R. N.;Moulick, N.",2011,,http://dx.doi.org/10.1136/bcr.04.2011.4121,0,0,
1677,Resolved psychosis after liver transplantation in a patient with wilson's disease,"A psychiatric involvement is frequently present in Wilson's disease. Psychiatric symptoms are sometimes the first and only manifestation of Wilson's disease. More often a psychiatric involvement is present beside a neurologic or hepatic disease. We describe the case of a 18 years-old male patient who shows a clinic and laboratoristic pattern of cirrhosis and an history of subchronic hallucinatory psychosis, behavioral symptoms and mood disturbances with depressed mood. He hadn't familiar history of liver or psychiatric disease. Laboratory and imaging tests confirmed the diagnosis of Wilson's disease with psichiatric involvement. After liver transplantation copper metabolism and liver function normalised and we noticed no recurrency of the psichiatric illness. Very few cases of psychiatric improvement after orthotopic liver transplantation (OLT) has been described until now. Copyright © Sorbello et al.; Licensee Bentham Open.",Copper metabolism;genetic liver disease;olt;psychiatric illness;psychosis;Wilson's disease.;adult;article;case report;ceruloplasmin blood level;copper blood level;human;liver transplantation;male;single photon emission computer tomography;Wilson disease/su [Surgery];young adult;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine;technetium 99m,"Sorbello, O.;Riccio, D.;Sini, M.;Carta, M.;Demelia, L.",2011,,,0,0,
1678,Neuro-Wilson disease - about seven cases and review of the literature,"Description Wilson disease is an autosomal recessive disorder of copper overlap, dominated by neuropsychiatric and hepatic symptoms. The aim of this study is to review the genetic aspects, diagnosis and treatment of Neuro-Wilson. Methods We report seven cases collected in the department of Neurology and Pediatrics CHU Hassan II of Fez. Results All patients had neurological signs with or without extra-neurological symptoms. They had complete blood count, liver function, renal balance, copper balance, brain imaging, abdominal ultrasound and upper gastrointestinal endoscopy. The diagnosis of Wilson's disease was based on clinical, biological and radiological results. Three patients were treated with D-penicillamin and the others received the zinc. The family survey in search of similar cases was carried out by clinical examination of siblings of four patients. Conclusion When left untreated, the evolution of Wilson's disease is always fatal. Treatment is based on the chelating copper, zinc salts and liver transplantation [7].The prognosis of Wilson's disease appears even better than the neurological and liver symptoms are not pronounced. © 2002-2012 African Journal of Neurological Sciences.",Cupric balance;D-penicillamin;Genetics;Keyser-fleischer ring;Neurological manifestations;Wilson disease;Zinc salts;blood cell count;clinical article;clinical examination;copper metabolism;echography;gastrointestinal endoscopy;human;liver function;Morocco;neuroimaging;review;sibling;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"El Machkour, M.;Babakhouya, A.;El Ouali, O.;Chouki, S.;Hida, M.;Maaroufi, M.;Belahsen, F. M.;Messouak, O.",2011,,,0,1,
1679,Reversal of severe Wilson arthropathy by liver transplantation,"Wilson disease is associated with multisystem involvement. We describe a patient of Wilson disease with severe arthropathy, which completely reversed following liver transplantation. This is the first case report in literature describing the complete reversal of Wilson disease related arthropathy by liver transplantation.",Arthropathy;Children;Copper;d-penicillamine;Wilson disease;arthropathy/dt [Drug Therapy];arthropathy/di [Diagnosis];article;blood analysis;case report;child;disease severity;drug substitution;human;knee radiography;laboratory test;liver transplantation;male;nuclear magnetic resonance imaging;school child;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];cyclosporin;opiate/dt [Drug Therapy];paracetamol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];steroid;tacrolimus;trientine/dt [Drug Therapy],"Nagral, A.;Sathe, K.",2011,May,http://dx.doi.org/10.1007/s13312-011-0063-4,0,0,
1680,Treatment of liver failure caused by Wilson's disease. [Czech],"The treatment of liver failure in a patient with acute manifestation of Wilson's disease is described in the case report. Twenty-three-year-old female patient was admitted with the decompensation of liver cirrhosis (originally of unknown aetiology) with the sings of liver failure (Child-Pugh C, 12 points). The suspicion to Wilson's disease was based on a history of the patient and high copper in urine. The diagnosis was confirmed by liver biopsy and subsequently by genetic examination. As the patient was obese with BMI 60, the consideration of liver transplantation was precluded. The patient was stabilized and liver function improved on maximal conservative treatment with concomitant treatment with chelating agents. The first choice penicillamine had to be exchanged for trientine due to allergy reaction and bone marrow suppression. 18 months after treatment initiation the patients is well, completely compensated with Child-Pugh A classification (5 points).",Cirrhosis;Liver failure;Penicillamine;Trientine;Wilson's disease;adult;allergic reaction/si [Side Effect];article;bone marrow suppression/si [Side Effect];case report;clinical feature;conservative treatment;differential diagnosis;drug substitution;female;human;liver failure/dt [Drug Therapy];liver failure/co [Complication];liver failure/di [Diagnosis];liver failure/et [Etiology];obesity;symptom;treatment outcome;Wilson disease/di [Diagnosis];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Petraskova, H.;Novak, F.;Humlova, R.;Bruha, R.",2011,,,0,0,
1681,Monitoring late complications of zinc treatment in Wilson's disease. Reply to the letter: Copper deficiency in Wilson's disease: An avoidable complication of treatment: Monitoring Late Complications of Zinc Treatment in Wilson's Disease,,chemical analysis;copper deficiency/co [Complication];cyanocobalamin deficiency;human;letter;motor dysfunction;peripheral neuropathy;priority journal;urinary excretion;Wilson disease;copper,"Cortese, A.;Zangaglia, R.;Lozza, A.;Piccolo, G.;Pacchetti, C.",2011,November,http://dx.doi.org/10.1002/mds.23969,0,0,
1682,Copper deficiency in Wilson's disease: An avoidable complication of treatment,,copper deficiency/co [Complication];human;letter;peripheral neuropathy;priority journal;Wilson disease/dt [Drug Therapy];n methyl dextro aspartic acid receptor 2A;zinc/dt [Drug Therapy],"Da Silva-Junior, F. P.;Lucato, L. T.;Machado, A. A. C.;Barbosa, E. R.",2011,November,http://dx.doi.org/10.1002/mds.23970,0,0,
1683,Metal attenuating therapies in neurodegenerative disease,"The clinical and pathological spectrum of neurodegenerative diseases is diverse, although common to many of these disorders is the accumulation of misfolded proteins, with oxidative stress thought to be an important contributing mechanism to neuronal damage. As a corollary, transition metal ion dyshomeostasis appears to play a key pathogenic role in a number of these maladies, including the most common of neurodegenerative diseases. In this review, studies spanning a wide variety of neurodegenerative disorders are presented with their involvement of transition metals compared and contrasted, including more detailed treatise in relation to Alzheimer's disease, Parkinson's disease and prion diseases. For each of these diseases, a discussion of the evolving scientific rationale for the development of therapies aimed at ameliorating the detrimental effects of transition metal dysregulation, including results from various human trials, is then provided. © 2011 Expert Reviews Ltd.",Alzheimer's disease;amyloid;brain;chelator;clioquinol;copper;hydroxyl radical;manganese;mpac;oxidative stress;Parkinson's disease;pbt2;prion;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];Alzheimer disease/th [Therapy];amyotrophic lateral sclerosis/et [Etiology];binding site;chelation therapy;degenerative disease/et [Etiology];Fenton reaction;Friedreich ataxia/dt [Drug Therapy];Friedreich ataxia/et [Etiology];Friedreich ataxia/th [Therapy];gene mutation;genetic association;Gerstmann Straussler Scheinker syndrome/dt [Drug Therapy];homeostasis;human;Huntington chorea/et [Etiology];iron chelation;lipid peroxidation;metal attenuating therapy;metal binding;mitochondrion;neurodegeneration with brain iron accumulation/et [Etiology];oligodendroglia;pantothenate kinase associated neurodegeneration/et [Etiology];Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];Parkinson disease/th [Therapy];prion disease/dt [Drug Therapy];prion disease/et [Etiology];prion disease/th [Therapy];protein aggregation;protein folding;protein phosphorylation;review;signal transduction;spinocerebellar degeneration/et [Etiology];systematic review;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha synuclein/ec [Endogenous Compound];aluminum;antioxidant/dt [Drug Therapy];antioxidant/pd [Pharmacology];ATM protein/ec [Endogenous Compound];beta secretase 1/ec [Endogenous Compound];bis(thiosemicarbazone)/pd [Pharmacology];cholinesterase inhibitor/dt [Drug Therapy];clioquinol/ct [Clinical Trial];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pd [Pharmacology];copper ion/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];deferoxamine/ct [Clinical Trial];deferoxamine/cb [Drug Combination];deferoxamine/dt [Drug Therapy];deferoxamine/im [Intramuscular Drug Administration];donepezil/dt [Drug Therapy];euk 189/dt [Drug Therapy];euk 189/pd [Pharmacology];huntingtin/ec [Endogenous Compound];iron/pd [Pharmacology];iron chelate/dt [Drug Therapy];iron chelate/pd [Pharmacology];isoniazid derivative/cb [Drug Combination];isoniazid derivative/dt [Drug Therapy];manganese/ec [Endogenous Compound];PBT2/ct [Clinical Trial];PBT2/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prion protein;pyrrolidine dithiocarbamate/pd [Pharmacology];reactive nitrogen species/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];tau protein/ec [Endogenous Compound];thiosemicarbazone derivative/pd [Pharmacology];transition element/ec [Endogenous Compound];trientine/dt [Drug Therapy];unclassified drug;zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Mot, A. I.;Wedd, A. G.;Sinclair, L.;Brown, D. R.;Collins, S. J.;Brazier, M. W.",2011,December,http://dx.doi.org/10.1586/ern.11.170,0,0,
1684,Treatment of elastosis perforans serpiginosa with the pinhole method using a carbon dioxide laser,,adult;article;carbon dioxide laser;case report;elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/su [Surgery];esthetics;female;human;hyperkeratosis/di [Diagnosis];hyperkeratosis/dt [Drug Therapy];hyperkeratosis/si [Side Effect];hyperkeratosis/su [Surgery];priority journal;punch biopsy;Wilson disease/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];corticosteroid/il [Intralesional Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Yang, J. H.;Han, S. S.;Won, C. H.;Chang, S. E.;Lee, M. W.;Choi, J. H.;Moon, K. C.",2011,April,http://dx.doi.org/10.1111/j.1524-4725.2011.01911.x,0,0,
1685,Transition metal homeostasis: From yeast to human disease,"Transition metal ions are essential nutrients to all forms of life. Iron, copper, zinc, manganese, cobalt and nickel all have unique chemical and physical properties that make them attractive molecules for use in biological systems. Many of these same properties that allow these metals to provide essential biochemical activities and structural motifs to a multitude of proteins including enzymes and other cellular constituents also lead to a potential for cytotoxicity. Organisms have been required to evolve a number of systems for the efficient uptake, intracellular transport, protein loading and storage of metal ions to ensure that the needs of the cells can be met while minimizing the associated toxic effects. Disruptions in the cellular systems for handling transition metals are observed as a number of diseases ranging from hemochromatosis and anemias to neurodegenerative disorders including Alzheimer's and Parkinson's disease. The yeast Saccharomyces cerevisiae has proved useful as a model organism for the investigation of these processes and many of the genes and biological systems that function in yeast metal homeostasis are conserved throughout eukaryotes to humans. This review focuses on the biological roles of iron, copper, zinc, manganese, nickel and cobalt, the homeostatic mechanisms that function in S. cerevisiae and the human diseases in which these metals have been implicated. © 2011 Springer Science+Business Media, LLC.",Cobalt;Copper;Human disease;Iron;Manganese;Nickel;Saccharomyces cerevisiae;Transition metal homeostasis;Zinc;Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/et [Etiology];article;concentration (parameters);degenerative disease/et [Etiology];disease association;Hailey Hailey disease/et [Etiology];hemochromatosis/et [Etiology];homeostasis;human;intoxication/et [Etiology];intracellular transport;Menkes syndrome/et [Etiology];metal binding;metal metabolism;molecular biology;neuroferritinopathy/et [Etiology];nonhuman;protein DNA binding;protein protein interaction;regulatory mechanism;Wilson disease/et [Etiology];zinc deficiency/et [Etiology];metal ion;transition element,"Bleackley, M. R.;MacGillivray, R. T. A.",2011,October,http://dx.doi.org/10.1007/s10534-011-9451-4,0,0,
1686,Association of Wilson's disease with neurofibromatosis,,Child;Neurofibromatosis;Wilson disease;aminotransferase blood level;article;case report;disease association;hemiparesis;histopathology;human;human tissue;liver disease;male;neurofibromatosis/dt [Drug Therapy];outcome assessment;pediatrics;school child;Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper chelating agent/dt [Drug Therapy];gamma glutamyltransferase/ec [Endogenous Compound];penicillamine;unclassified drug,"Sawamura, R.;Brunaldi, M. O.;Ramalho, L. N. Z.;Zucoloto, S.;Balancin, M. L.;Fernandes, M. I. M.",2011,,,0,0,
1687,Research tools and techniques for copper metabolism in mammals,"Copper (Cu) is an essential component of biological redox reactions and its deficiency is fatal to the body. At the same time, Cu is extremely toxic when present in excess. In this regard, several groups of Cu-regulating proteins in the body act to regulate the concentration of Cu within a certain range. However, the overall mechanism underlying the maintenance of Cu homeostasis in the body and cells remains poorly understood. In this review, recent research tools, such as animal models and gene-modified animals, and techniques, such as speciation and imaging of Cu, are highlighted. © 2011 The Pharmaceutical Society of Japan.",Chaperone;Copper;Imaging;Speciation;Alzheimer disease/dt [Drug Therapy];analytic method;chemical analysis;copper deficiency;copper metabolism;cystinuria/dt [Drug Therapy];drug binding;experimental animal;fluorescence analysis;fluorescence microscopy;gene mutation;high performance liquid chromatography;human;Huntington chorea/dt [Drug Therapy];laser ablation inductively coupled plasma mass spectrometry;mammal;mass spectrometry;mutant;nanoanalysis;nonhuman;review;rheumatoid arthritis/dt [Drug Therapy];scanning x ray fluorescence microscopy;species differentiation;transgenic animal;Wilson disease/dt [Drug Therapy];antibody;bathocuproine sulfonate/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/cm [Drug Comparison];unclassified drug,"Ogra, Y.",2011,,http://dx.doi.org/10.1248/jhs.57.385,0,0,
1688,Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease,"Background & Aims: Wilson disease is a genetic disorder that affects copper storage, leading to liver failure and neurologic deterioration. Patients are treated with copper chelators and zinc salts, but it is not clear what approach is optimal because there have been few studies of large cohorts. We assessed long-term outcomes of different treatments. Methods: Patients in tertiary care centers were retrospectively analyzed (n = 288; median follow-up time, 17.1 years) for adherence to therapy, survival, treatment failure, and adverse events from different treatment regimens (chelators, zinc, or a combination). Hepatic treatment failure was defined as an increase in activity of liver enzymes (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase) >2-fold the upper limit of normal or >100% of baseline with an increase in urinary copper excretion. Results: The median age at onset of Wilson disease was 17.5 years. Hepatic and neuropsychiatric symptoms occurred in 196 (68.1%) and 99 (34.4%) patients, respectively. Hepatic treatment failure occurred more often from zinc therapy (14/88 treatments) than from chelator therapy (4/313 treatments; P < .001). Actuarial survival, without transplantation, showed an advantage for chelating agents (P < .001 vs zinc). Changes in treatment resulted mostly from adverse events, but the frequency did not differ between groups. Patients who did not respond to zinc therapy showed hepatic improvement after reintroduction of a chelating agent. Conclusions: Treatments with chelating agents or zinc salt are effective in most patients with Wilson disease; chelating agents are better at preventing hepatic deterioration. It is important to identify patients who do not respond to zinc therapy and have increased activities of liver enzymes, indicating that a chelating agent should be added to the therapeutic regimen. © 2011 AGA Institute.",atp7b;d-penicillamine;Trientine;Triethylenetetramine;adult;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;chelation therapy;cohort analysis;deterioration;drug efficacy;drug treatment failure;drug withdrawal;enzyme activity;female;follow up;gamma glutamyl transferase blood level;human;liver failure/co [Complication];major clinical study;male;monotherapy;neurologic disease/co [Complication];patient compliance;priority journal;retrospective study;side effect/si [Side Effect];survival;treatment outcome;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];copper;gamma glutamyltransferase/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Weiss, K. H.;Gotthardt, D. N.;Klemm, D.;Merle, U.;Ferencifoerster, D.;Schaefer, M.;Ferenci, P.;Stremmel, W.",2011,April,http://dx.doi.org/10.1053/j.gastro.2010.12.034,1,1,
1689,Reorganizing Metals: The Use of Chelating Compounds as Potential Therapies for Metal-Related Neurodegenerative Disease,"Metal ions, particularly copper, zinc and iron, are implicated in several amyloidogenic neurodegenerative disorders. In the brain, as elsewhere in the body, metal ion excess or deficiency can potentially inhibit protein function, interfere with correct protein folding or, in the case of iron or copper, promote oxidative stress. The involvement of metal ions in neurodegenerative disorders has made them an emerging target for therapeutic interventions. One approach has been to chelate and sequester the ions and thus limit their potential to interfere with protein folding or render them unable to undergo redox processes. Newer approaches suggest that redistributing metal ions has therapeutic benefits, and recent studies indicate that alleviating cellular copper deficiency may be a plausible way to limit neurodegeneration. In this review we discuss the role of metals in amyloidogenic, neurodegenerative disorders and highlight some mechanisms and compounds used in various therapeutic approaches. © 2011 Bentham Science Publishers Ltd.","Alzheimer's;Chelator;Copper;Iron;Neurodegeneration;Parkinson's;Prion;Redox;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];Alzheimer disease/th [Therapy];amyloid neuropathy;article;copper deficiency;Creutzfeldt Jakob disease/et [Etiology];degenerative disease/et [Etiology];drug binding;drug bioavailability;drug withdrawal;fatal familial insomnia/et [Etiology];human;intestine infection/dt [Drug Therapy];oxidative stress;Parkinson disease;peptic ulcer/dt [Drug Therapy];protein folding;protein function;redox stress;rheumatoid arthritis/dt [Drug Therapy];side effect/si [Side Effect];structure activity relation;Wilson disease/dt [Drug Therapy];2,2' biquinoline/an [Drug Analysis];2,2' biquinoline/pd [Pharmacology];acetylcysteine amide/an [Drug Analysis];acetylcysteine amide/pd [Pharmacology];aluminum/ec [Endogenous Compound];chelating agent;cimetidine/an [Drug Analysis];cimetidine/dt [Drug Therapy];clioquinol/ae [Adverse Drug Reaction];clioquinol/an [Drug Analysis];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pk [Pharmacokinetics];clioquinol/pd [Pharmacology];copper/ec [Endogenous Compound];deferoxamine mesylate/an [Drug Analysis];deferoxamine mesylate/dt [Drug Therapy];dp 109/ct [Clinical Trial];dp 109/an [Drug Analysis];dp 109/pd [Pharmacology];epigallocatechin gallate/pd [Pharmacology];etoxazene/an [Drug Analysis];etoxazene/cm [Drug Comparison];etoxazene/pd [Pharmacology];euk 189/an [Drug Analysis];euk 189/pd [Pharmacology];euk 207/an [Drug Analysis];euk 207/pd [Pharmacology];iron/ec [Endogenous Compound];jkl 1291/an [Drug Analysis];jkl 1291/dt [Drug Therapy];jkl 169/an [Drug Analysis];jkl 169/dt [Drug Therapy];mepacrine/an [Drug Analysis];mepacrine/cm [Drug Comparison];mepacrine/pd [Pharmacology];metal complex/ec [Endogenous Compound];metal ion/ec [Endogenous Compound];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];prion protein/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];thiosemicarbazone/an [Drug Analysis];thiosemicarbazone/pd [Pharmacology];unclassified drug;zinc/ec [Endogenous Compound]","Badrick, A. C.;Jones, C. E.",2011,,http://dx.doi.org/10.2174/156802611794785181,0,0,
1690,Atypical presentation of Wilson disease,"A 15-year-old Caucasian female on human chorionic gonadotropin (HCG) diet presented with fever, cholestasis, coagulopathy, hemolytic anemia, and acute renal dysfunction. Imaging of the biliary system and liver were normal. She responded to intravenous antibiotics, vitamin K and blood transfusions but experienced relapse upon discontinuation of antibiotics. She had remission with reinstitution of antibiotics. Liver biopsy revealed pronounced bile ductular reaction, bridging fibrosis, and hepatocytic anisocytosis and anisonucleosis with degenerative enlarged eosinophilic hepatocytes, suggestive of Wilson disease. Diagnosis of Wilson disease was further established based on the low serum ceruloplasmin, increased urinary and hepatic copper and presence of Kayser-Fleischer rings. The multisystem involvement of the liver, kidney, blood, and brain are consistent with Wilson disease; however, the clinical presentation of cholangitis and reversible coagulopathy is uncommon, and may result from concurrent acute cholangitis and/or the HCG diet regimen the patient was on. Copyright © 2011 by Thieme Medical Publishers, Inc.",biliary;cholangitis;cholestasis;human chorionic gonadotropin diet;Wilson disease;abdominal radiography;acute kidney failure;adolescent;alpha 1 antitrypsin deficiency;ankle edema;ankle pain;arm swelling;article;aspartate aminotransferase blood level;bile duct dilatation/di [Diagnosis];bilirubin blood level;blood clotting disorder;blood pressure;blood transfusion;body temperature;body weight;breathing rate;case report;cell swelling;ceruloplasmin blood level;cholangitis/di [Diagnosis];cholangitis/dt [Drug Therapy];cholecystectomy;confusion;Coombs test;creatinine blood level;diet supplementation;disease association;disease course;emergency ward;eosinophil;eosinophilia/di [Diagnosis];erythrocyte concentrate;fatigue;fatty liver;female;ferritin blood level;fever;gallbladder disease/su [Surgery];headache;heart palpitation;heart rate;hematochezia;hematuria;hemolytic anemia;hospital admission;hospital discharge;human;human cell;human tissue;hyperthyroidism;hypoalbuminemia/di [Diagnosis];inflammatory infiltrate/di [Diagnosis];international normalized ratio;jaundice;knee pain;leukocyte;leukocytosis;liver biopsy;liver cell;mucosa;nausea;ovary cancer;ovary cyst/dt [Drug Therapy];priority journal;relapse;remission;rheumatoid arthritis;skin burning sensation;splenomegaly/di [Diagnosis];thyrotropin blood level;treatment outcome;urinalysis;urine volume;weight reduction;Wilson disease/di [Diagnosis];alkaline phosphatase/ec [Endogenous Compound];antibiotic agent/iv [Intravenous Drug Administration];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chorionic gonadotropin;ciprofloxacin/dt [Drug Therapy];ciprofloxacin/po [Oral Drug Administration];complement component C3/ec [Endogenous Compound];complement component C4/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];drospirenone plus ethinylestradiol/dt [Drug Therapy];drospirenone plus ethinylestradiol/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];furosemide;haptoglobin/ec [Endogenous Compound];hemosiderin;liver enzyme/ec [Endogenous Compound];metab;metronidazole/dt [Drug Therapy];Ocella;oral contraceptive agent;piperacillin plus tazobactam/dt [Drug Therapy];rhodanine;thyrotropin/ec [Endogenous Compound];tissue extract;trientine;unclassified drug;vitamin K group/iv [Intravenous Drug Administration],"Wadera, S.;Magid, M. S.;McOmber, M.;Carpentieri, D.;Miloh, T.",2011,,http://dx.doi.org/10.1055/s-0031-1286062,0,0,
1691,Critical assessment of Belgian reimbursement dossiers of orphan drugs,"Background: Orphan medicinal products are designed to diagnose or treat rare diseases that are serious, life threatening or chronically debilitating and that affect 50 or fewer people in every 100 000 in the EU. In Belgium, the Drug Reimbursement Committee (DRC) evaluates reimbursement requests for orphan drugs based on multiple criteria: the therapeutic value, price and proposed reimbursement tariff; the importance of the drug in clinical practice; and the budget impact of the drug. Objectives: This study aimed to assess reimbursement dossiers of orphan drugs in Belgium and to compare them with the clinical evidence submitted to the European Medicines Agency (EMA). Methods: A qualitative analysis examined all reimbursement dossiers of orphan drugs that were submitted in Belgium between January 2002 and June 2008. The following information was extracted from each dossier: description of the orphan drug; indication; reimbursement status; therapeutic value and needs; budget impact; and number of registered indications. For selected orphan drugs, an in-depth analysis extracted and compared information about the clinical trials, their primary endpoints and results from EMA documents (i.e. the marketing authorization application file, European public assessment report and summary of product characteristics) and the Belgian reimbursement dossiers. Results: Reimbursement was awarded to the majority of orphan drugs. In addition to the official criteria, other negotiable factors, such as price adjustments, employment incentives, patient population restrictions and funding of diagnostic tests by the company, seemed to play a role in the reimbursement decision. Despite the low number of patients, randomized controlled trials were conducted for many orphan drugs. Budget-impact analyses were simplistic and did not consider the impact across multiple indications. Some differences were also observed between the clinical evidence submitted to the EMA and that submitted to the Belgian DRC. Conclusions: In addition to the official criteria, other negotiable factors, such as price adjustments and employment incentives, may play a role in Belgian reimbursement decisions of orphan drugs. Some differences have also been noted between the clinical evidence reported in EMA documents and the evidence included in Belgian reimbursement dossiers of orphan drugs. There appears to be a need for further standardization of Belgian reimbursement applications and for European cooperation in sharing clinical evidence of orphan drugs. © 2011 Adis Data Information BV. All rights reserved.","Decision-making;Formularies;Health-policy;Reimbursement;acromegaly/dm [Disease Management];acromegaly/dt [Drug Therapy];acute lymphoblastic leukemia/dm [Disease Management];acute lymphoblastic leukemia/dt [Drug Therapy];adrenal cortex carcinoma/dm [Disease Management];adrenal cortex carcinoma/dt [Drug Therapy];article;Belgium;budget;chelation therapy;chronic disease/dt [Drug Therapy];chronic myeloid leukemia/dm [Disease Management];chronic myeloid leukemia/dt [Drug Therapy];chronic thromboembolic pulmonary hypertension/dm [Disease Management];chronic thromboembolic pulmonary hypertension/dt [Drug Therapy];clinical trial (topic);comparative study;controlled study;diagnostic test;drug cost;drug extravasation;drug indication;drug industry;Fabry disease/dm [Disease Management];Fabry disease/dt [Drug Therapy];funding;gastrointestinal tumor/dm [Disease Management];gastrointestinal tumor/dt [Drug Therapy];Gaucher disease/dm [Disease Management];Gaucher disease/dt [Drug Therapy];glycogen storage disease type 2/dt [Drug Therapy];hematopoietic stem cell transplantation;Hunter syndrome/dm [Disease Management];Hunter syndrome/dt [Drug Therapy];Hurler syndrome/dm [Disease Management];Hurler syndrome/dt [Drug Therapy];iron overload/dm [Disease Management];iron overload/dt [Drug Therapy];kidney carcinoma/dm [Disease Management];kidney carcinoma/dt [Drug Therapy];liver cell carcinoma/dm [Disease Management];liver cell carcinoma/dt [Drug Therapy];multiple myeloma/dm [Disease Management];multiple myeloma/dt [Drug Therapy];NAGS deficiency/dm [Disease Management];NAGS deficiency/dt [Drug Therapy];organization;Parkinson disease/dm [Disease Management];Parkinson disease/dt [Drug Therapy];personnel management;phase 1 clinical trial (topic);phase 2 clinical trial (topic);priority journal;promyelocytic leukemia/dm [Disease Management];promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dm [Disease Management];pulmonary hypertension/dt [Drug Therapy];qualitative analysis;randomized controlled trial (topic);risk reduction;sample size;thrombocytosis/dm [Disease Management];thrombocytosis/dt [Drug Therapy];tyrosinemia/dm [Disease Management];tyrosinemia/dt [Drug Therapy];Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];agalsidase alfa/ct [Clinical Trial];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/pe [Pharmacoeconomics];agalsidase beta/ct [Clinical Trial];agalsidase beta/dt [Drug Therapy];agalsidase beta/pe [Pharmacoeconomics];anagrelide/dt [Drug Therapy];anagrelide/pe [Pharmacoeconomics];antiparkinson agent/dt [Drug Therapy];antiparkinson agent/pe [Pharmacoeconomics];arsenic trioxide/dt [Drug Therapy];arsenic trioxide/pe [Pharmacoeconomics];bosentan/ct [Clinical Trial];bosentan/dt [Drug Therapy];bosentan/pe [Pharmacoeconomics];busulfan/ad [Drug Administration];busulfan/iv [Intravenous Drug Administration];busulfan/po [Oral Drug Administration];busulfan/pe [Pharmacoeconomics];carglumic acid/dt [Drug Therapy];carglumic acid/pe [Pharmacoeconomics];co careldopa/dt [Drug Therapy];co careldopa/pe [Pharmacoeconomics];dasatinib/dt [Drug Therapy];dasatinib/pe [Pharmacoeconomics];deferasirox/ct [Clinical Trial];deferasirox/dt [Drug Therapy];deferasirox/pe [Pharmacoeconomics];iduronate 2 sulfatase/ct [Clinical Trial];iduronate 2 sulfatase/dt [Drug Therapy];iduronate 2 sulfatase/pe [Pharmacoeconomics];imatinib/dt [Drug Therapy];imatinib/pe [Pharmacoeconomics];laronidase/ct [Clinical Trial];laronidase/dt [Drug Therapy];laronidase/pe [Pharmacoeconomics];lenalidomide/ct [Clinical Trial];lenalidomide/dt [Drug Therapy];lenalidomide/pe [Pharmacoeconomics];miglustat/dt [Drug Therapy];miglustat/pe [Pharmacoeconomics];mitotane/dt [Drug Therapy];mitotane/pe [Pharmacoeconomics];nelarabine/dt [Drug Therapy];nelarabine/pe [Pharmacoeconomics];nitisinone/dt [Drug Therapy];nitisinone/pe [Pharmacoeconomics];orphan drug/ct [Clinical Trial];orphan drug/ad [Drug Administration];orphan drug/dt [Drug Therapy];orphan drug/iv [Intravenous Drug Administration];orphan drug/po [Oral Drug Administration];orphan drug/pe [Pharmacoeconomics];pegvisomant/dt [Drug Therapy];pegvisomant/pe [Pharmacoeconomics];razoxane/pe [Pharmacoeconomics];recombinant glucan 1,4 alpha glucosidase/dt [Drug Therapy];recombinant glucan 1,4 alpha glucosidase/pe [Pharmacoeconomics];sildenafil/ct [Clinical Trial];sildenafil/dt [Drug Therapy];sildenafil/pe [Pharmacoeconomics];sitaxsentan/ct [Clinical Trial];sitaxsentan/dt [Drug Therapy];sitaxsentan/pe [Pharmacoeconomics];sorafenib/ct [Clinical Trial];sorafenib/dt [Drug Therapy];sorafenib/pe [Pharmacoeconomics];sunitinib/ct [Clinical Trial];sunitinib/dt [Drug Therapy];sunitinib/pe [Pharmacoeconomics];unclassified drug;zinc acetate/dt [Drug Therapy];zinc acetate/pe [Pharmacoeconomics]","Denis, A.;Mergaert, L.;Fostier, C.;Cleemput, I.;Hulstaert, F.;Simoens, S.",2011,,http://dx.doi.org/10.2165/11585980-000000000-00000,0,0,
1692,Wilson disease: Pathogenesis and clinical considerations in diagnosis and treatment,"Nearly a century after Dr. Samuel Alexander Kinnier Wilson composed his doctoral thesis on the pathologic findings of lenticular degeneration in the brain associated with cirrhosis of the liver we know that the underlying molecular basis for this autosomal recessive inherited disorder that now bears his name is mutation of a copper transporting ATPase, ATP7B, an intracellular copper transporter mainly expressed in hepatocytes. Loss of ATP7B function is the basis for reduced hepatic biliary copper excretion and reduced incorporation of copper into ceruloplasmin. During the intervening years, there was recognition of the clinical signs, histologic, biochemical features, and mutation analysis of ATP7B that characterize and enable diagnosis of this disorder. These include the presence of signs of liver or neurologic disease and detection of Kayser-Fleischer rings, low ceruloplasmin, elevated urine and hepatic copper, and associated histologic changes in the liver. Medical therapies and liver transplantation can effectively treat patients with this once uniformly fatal disorder. The earlier detection of the disease led to the initiation of treatment to prevent disease progression and reverse pathologic findings if present, and family screening to detect the disorder in first-degree relatives is warranted. Gene therapy and hepatocyte cell transplantation for Wilson disease has only been tested in animal models but represent future areas for study. Despite all the advances we still have to consider the diagnosis of Wilson disease to test patients for this disorder and properly establish the diagnosis before committing to life-long treatment. Copyright © 2011 by Thieme Medical Publishers, Inc.",atp7b;ceruloplasmin;copper;Kayser-Fleischer rings;Wilson disease;acute liver failure;adjuvant therapy;age;albumin blood level;amino acid substitution;aminoaciduria;aminotransferase blood level;amylase blood level;anemia;arthritis;article;behavior disorder;bleeding tendency;bone marrow suppression/si [Side Effect];brain edema;cataract;Caucasian;Chinese;chromosome 13;colitis/si [Side Effect];computer assisted tomography;creatine kinase blood level;differential diagnosis;disease marker;drug eruption/si [Side Effect];dysthymia;dystonia;Europe;exon;family counseling;family history;fever/si [Side Effect];fluid retention;gastrointestinal symptom/si [Side Effect];gene deletion;gene mutation;genetic screening;gynecomastia;hepatic encephalopathy;hepatography;hepatomegaly;heredity;homeostasis;human;hyperbilirubinemia;hypoparathyroidism;hypouricemia;incidence;Indian;infertility;international normalized ratio;jaundice;kayser fleischer ring;kidney failure;laboratory test;liver biopsy;liver cirrhosis;liver disease;liver fibrosis;liver histology;liver transplantation;lupus like syndrome/si [Side Effect];maintenance therapy;major depression;medical history;mental instability;mood disorder;muscle rigidity;myositis;nephrolithiasis;nephrotic syndrome/si [Side Effect];neuroimaging;neurologic examination;nuclear magnetic resonance imaging;osteopenia;parkinsonism;pathogenesis;physical examination;point mutation;Poland;portal hypertension;pregnancy;priority journal;prognosis;psychosocial withdrawal;Saudi Arabia;scoring system;sex difference;side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];spontaneous abortion;tremor;triacylglycerol lipase blood level;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];alpha tocopherol;aminotransferase/ec [Endogenous Compound];amylase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatine kinase/ec [Endogenous Compound];dimercaprol/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];serum albumin/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];triacylglycerol lipase/ec [Endogenous Compound];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Rosencrantz, R.;Schilsky, M.",2011,,http://dx.doi.org/10.1055/s-0031-1286056,0,0,
1693,Are some orphan drugs for rare diseases too expensive? A study of purchase versus compounding costs,"Hospital purchase prices substantially exceed compounding production costs in Belgium for selected orphan drugs that had low costs of research and development and market access procedures. As a result, healthcare payers seem to be paying too much for these orphan drugs and there are arguments for price reductions. Pharmacies can consider compounding, rather than purchasing, these orphan drugs. © 2011 Adis Data Information BV. All rights reserved.","article;Belgium;cost benefit analysis;cystinosis/dt [Drug Therapy];drug cost;Eaton Lambert syndrome/dt [Drug Therapy];glioblastoma/dt [Drug Therapy];health care cost;homocystinuria/dt [Drug Therapy];rare disease;urea cycle disorder/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];3,4 diaminopyridine/dt [Drug Therapy];3,4 diaminopyridine/pe [Pharmacoeconomics];4 phenylbutyric acid/dt [Drug Therapy];4 phenylbutyric acid/pe [Pharmacoeconomics];aminolevulinic acid/dt [Drug Therapy];aminolevulinic acid/pe [Pharmacoeconomics];betaine/dt [Drug Therapy];betaine/pe [Pharmacoeconomics];mercaptamine/dt [Drug Therapy];mercaptamine/pe [Pharmacoeconomics];orphan drug/pe [Pharmacoeconomics];zinc acetate/dt [Drug Therapy];zinc acetate/pe [Pharmacoeconomics]","Simoens, S.;Cassiman, D.;Picavet, E.;Dooms, M.",2011,October,http://dx.doi.org/10.2165/11601640-000000000-00000,0,0,
1694,Lingual dyskinesia and tics: A novel presentation of copper-metabolism disorder,"Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology. Copyright © 2011 by the American Academy of Pediatrics.",Copper;Lingual dyskinesia;Metabolic diseases;Metabolic disorders;Movement disorders;Tics;adolescent;article;case report;ceruloplasmin blood level;copper blood level;copper metabolism;differential diagnosis;hemiballism;human;male;metabolic disorder;motor dysfunction;neurologic examination;nuclear magnetic resonance imaging;orofacial dyskinesia;pathophysiology;priority journal;tic;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];gluconate zinc/po [Oral Drug Administration];penicillamine,"Goez, H. R.;Jacob, F. D.;Yager, J. Y.",2011,February,http://dx.doi.org/10.1542/peds.2010-2391,0,0,
1695,Improvement of renal functions after embolization of renal AVF in a patient who had been on dialysis for 5 years,"Recently, ultrasound-guided percutaneous renal biopsy has been used in the diagnosis of renal diseases. Development of an arteriovenous fistula (AVF), which is one of the post-biopsy complications, is not frequently encountered. AVFs are usually asymptomatic; however, they may lead to serious outcomes. We report a 21-year-old patient, who had been on dialysis for 5 years. Due to high blood pressure (230/160 mmHg) and a thrill in the lumbar area detected on physical examination, Doppler examination was performed and a renal AVF was detected. Because the patient had a history of renal biopsy 5 years previously, the fistula was thought to be secondary to the biopsy. After embolization of the AVF, renal functions improved enough to terminate dialysis treatment. © Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2010.",Arteriovenous fistula;Embolization;Renal arteriovenous fistula;Symptomatic;adult;article;artificial embolism;case report;central nervous system disease/dt [Drug Therapy];clinical feature;creatinine clearance;Doppler echography;hemodialysis;human;hypertension/dt [Drug Therapy];hypervolemia/th [Therapy];kidney arteriovenous fistula/co [Complication];kidney arteriovenous fistula/di [Diagnosis];kidney arteriovenous fistula/th [Therapy];kidney function;liver disease/dt [Drug Therapy];male;outcome assessment;physical examination;priority journal;treatment duration;treatment response;uremia/th [Therapy];Wilson disease/dt [Drug Therapy];amlodipine/cb [Drug Combination];amlodipine/dt [Drug Therapy];creatinine/ec [Endogenous Compound];doxazosin/cb [Drug Combination];doxazosin/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ulusoy, S.;Ozkan, G.;Dinc, H.;Kaynar, K.;Ozturk, M. H.;Gul, S.;Kaplan, S. T.",2011,February,http://dx.doi.org/10.1007/s00270-010-9970-3,0,0,
1696,Severe neuropsychiatric presentation of Wilson's disease,"Wilson's disease (WD) is a relatively rare disease of copper metabolism. The diagnosis is often missed initially. The presentation is usually neurologic or hepatic, seen in 40% of patients. Psychiatric presentation of WD is reported in only 15% of patients. We present a 32-year-old patient with severe psychiatric manifestations. On examination, he had mild rest and postural tremors and a KF ring was seen. Serum ceruloplasmin was low and 24-hour urinary copper was elevated. The patient responded to penicillamine, lorazepam and quetiapine, and is being followed up.",Hepatolenticular degeneration;Neurologic;Neuropsychiatric presentation;Penicillamine;Wilson's disease;adult;aggressiveness;article;attention disturbance;behavior disorder;bradykinesia;case report;ceruloplasmin blood level;copper blood level;delusion;disease severity;drug dose increase;drug dose reduction;drug substitution;drug withdrawal;extrapyramidal symptom/dt [Drug Therapy];extrapyramidal symptom/si [Side Effect];eye examination;follow up;hand tremor/dt [Drug Therapy];hospital patient;human;inattention tremor/dt [Drug Therapy];inhibition (psychology);limb tremor/dt [Drug Therapy];male;mental disease/dt [Drug Therapy];mental instability;Mini Mental State Examination;muscle rigidity;neuropsychiatry;nuclear magnetic resonance imaging;personality disorder;physical disease;postural tremor/dt [Drug Therapy];restlessness/dt [Drug Therapy];sardonic grin;tablet;tremor/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];haloperidol/dt [Drug Therapy];haloperidol/im [Intramuscular Drug Administration];lorazepam/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine;quetiapine/dt [Drug Therapy];sedative agent/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy],"Chakor, R. T.;Santhosh, N. S.",2011,April-June,http://dx.doi.org/10.4103/0019-5545.82556,0,0,
1697,DNA and RNA studies for molecular characterization of a gross deletion detected in homozygosity in the NH2-terminal region of the ATP7B gene in a Wilson disease patient,"Wilson disease is an autosomal recessive disorder caused by defective function of the copper transporting protein ATP7B. Approximately 520 Wilson disease-causing mutations have been described to date. In this study we report the use of DNA and RNA analysis for molecular characterization of a gross deletion of the ATP7B gene detected in homozygosity in a Wilson disease patient. The c.51+384_1708-953del mutation spans an 8798 bp region of the ATP7B gene from exon 2 to intron 4. The results obtained suggest that the combination of DNA and RNA analyses can be used for molecular characterization of gross ATP7B deletions, thus improving genetic counselling and diagnosis of Wilson disease. Moreover these studies, help to better establish the molecular mechanisms producing Wilson disease. © 2011.",atp7b;dna;Molecular diagnosis;rna;Wilson disease;amino terminal sequence;article;brain disease/dt [Drug Therapy];child;drug withdrawal;exon;gene deletion;genetic counseling;homozygosity;human;intron;male;priority journal;RNA analysis;school child;treatment outcome;Wilson disease/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];DNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];RNA/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Incollu, S.;Lepori, M. B.;Zappu, A.;Dessi, V.;Noli, M. C.;Mameli, E.;Iorio, R.;Ranucci, G.;Cao, A.;Loudianos, G.",2011,October,http://dx.doi.org/10.1016/j.mcp.2011.07.003,0,0,
1698,Rheumatic manifestations associated with Wilson's disease. [French],"Wilson's disease (WD) is a rare disease, defined as an autosomal recessive disorder characterized by release of free copper and dramatic accumulation of intracellular hepatic copper with subsequent hepatic and central nervous system abnormalities. Mutations of the ATP7B gene are responsible for the metabolic disease. Limited number of small studies allow to spinal radiological abnormalities include diffuse bone demineralisation, osteochondritis, and occasionally fractures. In one prospective study, prevalence of osteoporosis was 10%, with normal mean Z-score values, and prevalence of past history of fractures was 50%. Articular disorders encompass arthralgias of large joints, such as knee pain, rare effusions, early onset of radiological features of osteoarthritis, and associated osteochondritis. Some patients may develop drug-induced lupus with arthralgias, positive antinuclear and antihistone antibodies, secondary to D-penicillamine, the major copper chelator used in WD. In this uncommon disease, small retrospective studies cannot allow to ascertain definite WD-related articular and bone manifestations. Such clinical and radiological abnormalities are occasionally the first symptoms leading to diagnosis. However unexplained joint pain and effusion of the large joints in adolescents could suggest WD and lead to copper survey. Bone disease and fractures management are common to those applied in the general population. © 2011 Societe francaise de rhumatologie.",Arthralgia;Bone mineral density;Fracture;Osteoarthritis;Osteoporosis;Wilson's disease;arthralgia/si [Side Effect];arthropathy/co [Complication];ATP7B gene;bone demineralization;cervical spine radiography;gene;gene mutation;human;joint effusion/co [Complication];knee pain/co [Complication];lupus like syndrome/si [Side Effect];osteochondritis;prevalence;short survey;side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];antinuclear antibody/ec [Endogenous Compound];copper/ec [Endogenous Compound];histone antibody/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Quemeneur, A. S.;Trocello, J. M.;de Vernejoul, M. C.;Woimant, F.;Liote, F.",2011,September,http://dx.doi.org/10.1016/j.monrhu.2011.05.002,0,0,
1699,Neurological Wilson's disease with refractory rickets,Wilson's disease rarely presents with isolated neurological complaints without any hepatic involvement. Refractory rickets with Wilson's disease has been infrequently reported in literature. We are reporting a case of isolated neurological Wilson's disease associated with refractory rickets which on complete evaluation was diagnosed as familial hypophosphatemic rickets. © 2011 by Walter de Gruyter Berlin New York 2011.,neurological Wilson's disease;rickets.;adolescent;article;case report;disease association;dysarthria/di [Diagnosis];human;hypophosphatemic rickets/dt [Drug Therapy];hypophosphatemic rickets/di [Diagnosis];inattention tremor/di [Diagnosis];male;medical history;mental instability/di [Diagnosis];neurologic examination;tremor/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];X ray;calcitriol/dt [Drug Therapy];Joulie solution/dt [Drug Therapy];phosphorus/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];unclassified drug;zinc/dt [Drug Therapy],"Kaur, S.;Maheshwari, A.;Aneja, S.;Patra, S.;Krishnamurthy, S.;Seth, A.",2011,01 Apr,http://dx.doi.org/10.1515/JPEM.2011.094,0,0,
1700,Acute nonimmune hemolytic anemia without fulminant hepatitis in Wilson disease,"Owing to the insidious course and variable presentation, Wilson disease is often diagnosed months to years after the initial symptoms. Although fulminant hepatitis with nonimmune hemolytic anemia is frequently reported, chronic mild hepatitis can occur with bouts of transient hemolytic anemia. We report a 16-year-old female who presented with fatigue, dizziness, and new onset jaundice. She had a hemolytic anemia, although diagnosis of Wilson disease was initially confounded by a family history of autoimmunity with a high erythrocyte sedimentation rate and only mildly elevated bilirubin and aspartate aminotransferase. Macrocytosis, poor liver synthetic function, and low serum alkaline phosphatase led to the diagnosis. Copyright © 2011 by Lippincott Williams & Wilkins.",hepatitis;nonimmune hemolytic anemia;Wilson disease;acute nonimmune hemolytic anemia/di [Diagnosis];acute nonimmune hemolytic anemia/th [Therapy];adolescent;albumin blood level;article;autoimmune hemolytic anemia/di [Diagnosis];autoimmunity;bilirubin blood level;blood clotting disorder;case report;Coombs test;differential diagnosis;dizziness;enzyme blood level;erythrocyte sedimentation rate;family history;fatigue;female;hemolytic anemia/di [Diagnosis];hemolytic anemia/th [Therapy];human;jaundice;liver biopsy;liver function test;megalocytosis;priority journal;prothrombin time;vitamin supplementation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];blood clotting factor 7/ec [Endogenous Compound];blood clotting factor 8/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];haptoglobin/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];prothrombin/ec [Endogenous Compound],"Agrawal, A. K.;Haddad, F. G.;Matsunaga, A.",2011,May,http://dx.doi.org/10.1097/MPH.0b013e3182122422,0,0,
1701,Teratogenic exposures,"A consideration of teratogenic exposures includes not only an agent (chemical, radiation, biologic) but an exposure level and timing of exposure. There are criteria by which exposures are evaluated for a causal connection with an abnormal outcome. We here review some teratogenic exposures and discuss how they were initially described and confirmed. We have limited our discussion to some of the exposures for which a connection to structural malformations has been accepted in some quarters, and we indicate some exposures for which a causal association awaits confirmation. We recommend that counselors find a reliable and updatable source of information on exposures during pregnancy. © 2011 Wiley-Liss, Inc.",Angiotensin converting enzyme inhibitors;Carbamzepine;Diethylstilbestrol;Ethanol;Isotretinoin;Lithium;Methimazole;Misoprostol;Mycophenolate mofetil;Penicillamine;Phenytoin;Rubella;Teratogenic exposures;Thalidomide;Toluene;Valproic acid;Varicella;Warfarin;X-ray;acne cystica/dt [Drug Therapy];alcoholism;anencephalus/si [Side Effect];angiogenesis;anotia/si [Side Effect];anuria/si [Side Effect];aorta anomaly/si [Side Effect];arthrogryposis/si [Side Effect];arthropathy/si [Side Effect];article;bipolar disorder/dt [Drug Therapy];birth defect/si [Side Effect];blood pressure;bone malformation/si [Side Effect];brain malformation/si [Side Effect];brain necrosis/si [Side Effect];cataract/si [Side Effect];central nervous system malformation/si [Side Effect];chicken;chickenpox;cleft lip/si [Side Effect];cleft palate/si [Side Effect];clubfoot/si [Side Effect];coloboma/si [Side Effect];combination chemotherapy;conduction deafness/si [Side Effect];congenital heart malformation/si [Side Effect];congenital malformation/cn [Congenital Disorder];congenital malformation/si [Side Effect];connective tissue disease/si [Side Effect];corpus callosum agenesis/si [Side Effect];cranial neuropathy/si [Side Effect];craniofacial malformation/si [Side Effect];craniofacial synostosis/si [Side Effect];cryptorchism/si [Side Effect];cystinuria/dt [Drug Therapy];cytomegalovirus infection;developmental disorder/si [Side Effect];diaphragm hernia/si [Side Effect];dose response;drug absorption;drug dose increase;drug elimination;drug excretion;drug fatality/si [Side Effect];drug half life;drug megadose;drug metabolism;drug structure;drug withdrawal;duodenoum atresia/si [Side Effect];duodenum disease/si [Side Effect];ear malformation/si [Side Effect];Ebstein anomaly/si [Side Effect];ectopic kidney/si [Side Effect];ectopic pregnancy/dt [Drug Therapy];electromagnetic radiation;embryopathy/si [Side Effect];embryotoxicity/si [Side Effect];epicanthus;epididymal cyst/si [Side Effect];epilepsy/dt [Drug Therapy];erythema nodosum leprosum/dt [Drug Therapy];esophagus atresia/si [Side Effect];experimental mouse;experimental rabbit;experimental rat;external ear malformation/si [Side Effect];eye malformation/si [Side Effect];face deformity/si [Side Effect];face malformation/si [Side Effect];facial cleft/si [Side Effect];facial hemangiomata/si [Side Effect];facial nerve paralysis/si [Side Effect];Fallot tetralogy/si [Side Effect];female genital tract malformation/si [Side Effect];fetal alcohol syndrome;fetal hydantoin syndrome/si [Side Effect];fetotoxicity/si [Side Effect];fetus blood pressure/si [Side Effect];fetus death;fetus development;fetus disease/si [Side Effect];fetus malformation/si [Side Effect];finger malformation/si [Side Effect];first trimester pregnancy;growth retardation/si [Side Effect];hair disease/si [Side Effect];heart arrhythmia/dt [Drug Therapy];heart atrium septum defect/si [Side Effect];heart valve prosthesis;heart ventricle septum defect/si [Side Effect];hepatosplenomegaly;herpes simplex;human;hydramnios/si [Side Effect];hydrocephalus/si [Side Effect];hydronephrosis/si [Side Effect];hydrops/si [Side Effect];hypertelorism/si [Side Effect];hyperthyroidism/dt [Drug Therapy];hypocalvaria/si [Side Effect];hypospadias/si [Side Effect];hypotension/si [Side Effect];infertility/si [Side Effect];inguinal hernia/si [Side Effect];intelligence quotient;intestine malrotation/si [Side Effect];intrauterine growth retardation/si [Side Effect];ionizing radiation;jaundice;joint hyperflexibility/si [Side Effect];joint malformation/si [Side Effect];kidney agenesis/si [Side Effect];kidney dysplasia/si [Side Effect];kidney failure/si [Side Effect];kidney function;kidney malformation/si [Side Effect];lax skin/si [Side Effect];limb defect/si [Side Effect];limb malformation/si [Side Effect];listeriosis;low birth weight/si [Side Effect];low drug dose;low set ear/si [Side Effect];lumbar meningomyelocele/si [Side Effect];lung hypoplasia/si [Side Effect];measles;meningomyelocele/si [Side Effect];mental deficiency/si [Side Effect];mental development;meromelia/si [Side Effect];microcephaly/si [Side Effect];micrognathia/si [Side Effect];microphthalmia/si [Side Effect];microtia/si [Side Effect];migraine/dt [Drug Therapy];monotherapy;motor development;mouth malformation/si [Side Effect];multiple myeloma/dt [Drug Therapy];muscle hypotonia/si [Side Effect];nail disease/si [Side Effect];neck malformation/si [Side Effect];neoplasm/dt [Drug Therapy];neuroblastoma/si [Side Effect];neuroectoderm tumor/si [Side Effect];nonhuman;nose hypoplasia/si [Side Effect];nose malformation/si [Side Effect];occupational exposure;oligohydramnios/si [Side Effect];optic nerve atrophy/si [Side Effect];orchitis/si [Side Effect];palate malformation/si [Side Effect];parvovirus infection;patent ductus arteriosus/si [Side Effect];petechia;phalanx hypoplasia/si [Side Effect];phocomelia/si [Side Effect];placental transfer;polydactyly/si [Side Effect];postpartum hemorrhage/dt [Drug Therapy];premature labor/si [Side Effect];prematurity/dt [Drug Therapy];prematurity/pc [Prevention];prenatal exposure;priority journal;psoriasis/dt [Drug Therapy];pulmonary valve stenosis/si [Side Effect];radiation dose;radius aplasia/si [Side Effect];rheumatoid arthritis/dt [Drug Therapy];rib malformation/si [Side Effect];risk assessment;rubella/dt [Drug Therapy];rubella/pc [Prevention];sacral dimple/si [Side Effect];scalp malformation/si [Side Effect];seizure;short nose/si [Side Effect];side effect/si [Side Effect];skin aplasia/si [Side Effect];skin malformation/si [Side Effect];skull malformation/si [Side Effect];spatial orientation;spina bifida/si [Side Effect];spontaneous abortion/dt [Drug Therapy];spontaneous abortion/pc [Prevention];spontaneous abortion/si [Side Effect];stomach ulcer/dt [Drug Therapy];stomach ulcer/pc [Prevention];syndactyly/si [Side Effect];syphilis;systemic lupus erythematosus/dt [Drug Therapy];teratogenesis;teratogenicity/si [Side Effect];tethered foreskin/si [Side Effect];third trimester pregnancy;thrombocytopenia;thumb malformation/si [Side Effect];thymus disease/si [Side Effect];thymus malformation/si [Side Effect];thyroid disease/si [Side Effect];tooth malformation/si [Side Effect];toxoplasmosis;tracheoesophageal fistula/si [Side Effect];treatment withdrawal;trigeminus neuralgia/dt [Drug Therapy];umbilical hernia/si [Side Effect];urogenital tract malformation/si [Side Effect];uterus cervix malformation/si [Side Effect];uterus hypoplasia/si [Side Effect];uterus malformation/si [Side Effect];vagina adenocarcinoma/si [Side Effect];vagina carcinoma/si [Side Effect];vertebra malformation/si [Side Effect];vision;Wilson disease/dt [Drug Therapy];wound healing impairment/si [Side Effect];alcohol/to [Drug Toxicity];aminopterin/ae [Adverse Drug Reaction];captopril/ae [Adverse Drug Reaction];carbamazepine/ae [Adverse Drug Reaction];carbamazepine/do [Drug Dose];carbamazepine/dt [Drug Therapy];carbimazole/ae [Adverse Drug Reaction];chemical teratogen;diethylstilbestrol/ae [Adverse Drug Reaction];diethylstilbestrol/dt [Drug Therapy];dipeptidyl carboxypeptidase inhibitor/ae [Adverse Drug Reaction];etretin/pk [Pharmacokinetics];etretinate/ae [Adverse Drug Reaction];etretinate/pk [Pharmacokinetics];isotretinoin/ae [Adverse Drug Reaction];isotretinoin/dt [Drug Therapy];isotretinoin/pk [Pharmacokinetics];isotretinoin/tp [Topical Drug Administration];lamotrigine/ae [Adverse Drug Reaction];lithium/ae [Adverse Drug Reaction];live vaccine/dt [Drug Therapy];methotrexate/ae [Adverse Drug Reaction];methotrexate/an [Drug Analysis];methotrexate/cb [Drug Combination];methotrexate/dt [Drug Therapy];mifepristone/cb [Drug Combination];misoprostol/ae [Adverse Drug Reaction];misoprostol/cb [Drug Combination];misoprostol/dt [Drug Therapy];mycophenolic acid/ae [Adverse Drug Reaction];mycophenolic acid 2 morpholinoethyl ester/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];phenobarbital/ae [Adverse Drug Reaction];phenobarbital/cb [Drug Combination];phenobarbital/dt [Drug Therapy];phenytoin/ae [Adverse Drug Reaction];phenytoin/cb [Drug Combination];phenytoin/dt [Drug Therapy];rubella vaccine/dt [Drug Therapy];thalidomide/ae [Adverse Drug Reaction];thalidomide/dt [Drug Therapy];thalidomide/to [Drug Toxicity];thalidomide/iv [Intravenous Drug Administration];thalidomide/po [Oral Drug Administration];thiamazole/ae [Adverse Drug Reaction];thiamazole/dt [Drug Therapy];toluene/to [Drug Toxicity];topiramate/ae [Adverse Drug Reaction];valproic acid/ae [Adverse Drug Reaction];valproic acid/cb [Drug Combination];valproic acid/dt [Drug Therapy];valproic acid/to [Drug Toxicity];warfarin/ae [Adverse Drug Reaction];warfarin/po [Oral Drug Administration];warfarin/pk [Pharmacokinetics],"Obican, S.;Scialli, A. R.",2011,15 August,http://dx.doi.org/10.1002/ajmg.c.30310,0,0,
1702,Positive outcome in a patient with Wilson's disease treated with reduced zinc dosage in pregnancy,,adult;case report;ceruloplasmin blood level;copper blood level;drug dose reduction;drug efficacy;drug monitoring;dysarthria;female;fetus development;human;letter;liver level;low drug dose;muscle rigidity;nuclear magnetic resonance imaging;patient compliance;pregnancy;priority journal;treatment outcome;tremor;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc blood level;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];zinc/cr [Drug Concentration];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy],"Masciullo, M.;Modoni, A.;Bianchi, M. L. E.;De Carolis, S.;Silvestri, G.",2011,November,http://dx.doi.org/10.1016/j.ejogrb.2011.06.040,0,0,
1703,Copper deficiency myeloneuropathy in a patient with wilson disease,,adult;case report;ceruloplasmin blood level;copper blood level;copper deficiency/si [Side Effect];copper deficiency/di [Diagnosis];copper deficiency myeloneuropathy/di [Diagnosis];copper deficiency myeloneuropathy/si [Side Effect];depression;drug substitution;drug withdrawal;dysarthria;electromyography;female;human;leukopenia;megalocytosis;neurologic examination;neuropathy/si [Side Effect];neuropathy/di [Diagnosis];paresthesia;priority journal;short survey;thrombocytopenia;tremor;unspecified side effect/si [Side Effect];urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc blood level;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cyanocobalamin/po [Oral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc/ec [Endogenous Compound];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy],"Da Silva-Junior, F. P.;MacHado, A. A. C.;Lucato, L. T.;Cancado, E. L. R.;Barbosa, E. R.",2011,10 May,http://dx.doi.org/10.1212/WNL.0b013e318219fac8,0,0,
1704,Alzheimer's disease & metals: Therapeutic opportunities,"Alzheimer's disease (AD) is the most common age related neurodegenerative disease. Currently, there are no disease modifying drugs, existing therapies only offer short-term symptomatic relief. Two of the pathognomonic indicators of AD are the presence of extracellular protein aggregates consisting primarily of the Abeta peptide and oxidative stress. Both of these phenomena can potentially be explained by the interactions of Abeta with metal ions. In addition, metal ions play a pivotal role in synaptic function and their homeostasis is tightly regulated. A breakdown in this metal homeostasis and the generation of toxic Abeta oligomers are likely to be responsible for the synaptic dysfunction associated with AD. Therefore, approaches that are designed to prevent Abeta metal interactions, inhibiting the formation of toxic Abeta species as well as restoring metal homeostasis may have potential as disease modifying strategies for treating AD. This review summarizes the physiological and pathological interactions that metal ions play in synaptic function with particular emphasis placed on interactions with Abeta. A variety of therapeutic strategies designed to address these pathological processes are also described. The most advanced of these strategies is the so-called 'metal protein attenuating compound' approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. The success of these various strategies suggests that manipulating metal ion interactions offers multiple opportunities to develop disease modifying therapies for AD. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.",amyloid;bioinorganic chemistry;chelator;copper;drug;homeostasis;oxidative stress;synaptic toxicity;zinc;Alzheimer disease/dt [Drug Therapy];binding site;cancer risk;cognitive defect/si [Side Effect];drug binding;drug efficacy;drug mechanism;drug safety;drug targeting;drug tolerability;hemochromatosis/dt [Drug Therapy];human;neurotoxicity;neurotransmission;nonhuman;priority journal;protein interaction;protein structure;review;side effect/si [Side Effect];synapse;Wilson disease/dt [Drug Therapy];amyloid beta protein/to [Drug Toxicity];amyloid beta protein/ec [Endogenous Compound];cholinesterase inhibitor/dt [Drug Therapy];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pd [Pharmacology];copper ion/ec [Endogenous Compound];deferoxamine/dt [Drug Therapy];metal chelate/pd [Pharmacology];metal complex/ct [Clinical Trial];metal complex/dt [Drug Therapy];metal complex/pd [Pharmacology];metal ion/ec [Endogenous Compound];n methyl dextro aspartic acid receptor blocking agent/dt [Drug Therapy];PBT2/ct [Clinical Trial];PBT2/dt [Drug Therapy];PBT2/pd [Pharmacology];penicillamine/dt [Drug Therapy];placebo;platinum complex/an [Drug Analysis];platinum complex/pd [Pharmacology];semagacestat/ae [Adverse Drug Reaction];semagacestat/ct [Clinical Trial];semagacestat/dt [Drug Therapy];thiosemicarbazone derivative/an [Drug Analysis];thiosemicarbazone derivative/pd [Pharmacology];trientine/dt [Drug Therapy];unclassified drug;zinc ion/ec [Endogenous Compound],"Kenche, V. B.;Barnham, K. J.",2011,May,http://dx.doi.org/10.1111/j.1476-5381.2011.01221.x,0,0,
1705,Wilson's disease only presenting with isolated unilateral resting tremor,,adult;case report;clinical feature;computer assisted tomography;copper blood level;diagnostic error;human;inattention tremor;letter;liver biopsy;male;mutational analysis;nuclear magnetic resonance imaging;priority journal;slit lamp;symptomatology;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Jang, W.;Cho, J.;Kim, J. S.;Kim, H. T.",2011,01 Nov,,0,0,
1706,Integration of metabolomics in heart disease and diabetes research: Current achievements and future outlook,"Metabolomics is an emerging and powerful discipline that provides an accurate and dynamic picture of the phenotype of mammalian systems through the study of endogenous and exogenous metabolites in cells, tissues, culture supernatants as well as biofluids. In the last 5 years an increase in the number of metabolomic investigations of cardiovascular diseases and diabetes has been observed. In this article the experimental strategies applied and recent examples of their application in disease and drug efficacy/toxicity biomarker detection and the employment for the discovery of new molecular pathophysiological processes related to disease onset and progression, as well as their usefulness in drug efficacy/toxicity, will be reviewed. An outlook of the requirements for future successes will also be discussed. © 2011 Future Science Ltd.","abdominal aorta aneurysm;atherogenesis;cardiomyopathy;cardiotoxicity/dt [Drug Therapy];cardiotoxicity/si [Side Effect];cardiovascular disease/dt [Drug Therapy];cardiovascular disease/di [Diagnosis];cardiovascular disease/et [Etiology];cardiovascular risk;cell metabolism;Chinese medicine;coronary artery disease;diabetes mellitus/dt [Drug Therapy];diabetic retinopathy;diabetogenesis;dietary intake;disease association;disease course;disease marker;disease severity;drug efficacy;drug safety;genomics;heart failure;heart hypertrophy/dt [Drug Therapy];heart infarction/dt [Drug Therapy];high throughput screening;human;impaired glucose tolerance;insulin dependent diabetes mellitus/di [Diagnosis];insulin dependent diabetes mellitus/dt [Drug Therapy];insulin dependent diabetes mellitus/et [Etiology];insulin resistance;intestine flora;malignant neoplastic disease/dt [Drug Therapy];medical research;metabolite;metabolomics;molecular biology;molecular pathology;mortality;non insulin dependent diabetes mellitus/di [Diagnosis];non insulin dependent diabetes mellitus/et [Etiology];nonhuman;nuclear magnetic resonance spectroscopy;pathophysiology;peripheral vascular disease;prognosis;proteomics;review;single drug dose;systems biology;Wilson disease/dt [Drug Therapy];2,4 thiazolidinedione derivative/dt [Drug Therapy];amino acid;biological marker;cardiovascular agent/dt [Drug Therapy];celecoxib;doxorubicin/ae [Adverse Drug Reaction];doxorubicin/do [Drug Dose];doxorubicin/to [Drug Toxicity];fibric acid derivative;hydrolase inhibitor/dt [Drug Therapy];hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy];insulin/cm [Drug Comparison];insulin/dt [Drug Therapy];leptin/cm [Drug Comparison];metformin;nutraceutical/dt [Drug Therapy];phenol derivative/dt [Drug Therapy];phosphotransferase inhibitor/ae [Adverse Drug Reaction];phosphotransferase inhibitor/dt [Drug Therapy];rofecoxib/to [Drug Toxicity];rofecoxib/po [Oral Drug Administration];rosiglitazone;Rosmarinus officinalis extract/dt [Drug Therapy];soluble epoxide hydrolase inhibitor/dt [Drug Therapy];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];unclassified drug","Dunn, W. B.;Goodacre, R.;Neyses, L.;Mamas, M.",2011,October,http://dx.doi.org/10.4155/bio.11.223,0,0,
1707,Event related potentials and cognitive evaluation in Wilson's disease with and without neurological manifestation. [Turkish],"A cognitive impairment profile with the 'Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, multi-infarct dementia, and dementias of other etiology' (SIDAM) including Mini-Mental State Examination (MMSE) as well as auditory evoked P300 potentials were performed in 35 adult patients with Wilson's disease. Patients with a neurological course of the disease by trend showed lower amplitudes, delayed latencies of P300 and lower values in the cognitive tests but all median results were still at a normal range without correlation of cognitive decline to the extent of neurological impairment. The possibility of mild cognitive impairment in Wilson's disease is discussed.",Cognitive impairment;Event related potentials;p300;Wilson's disease;adult;aged;article;ataxia;bradykinesia;clinical article;cognitive defect/di [Diagnosis];dementia;dysarthria;event related potential;evoked auditory response;extrapyramidal symptom;female;gait disorder;human;hypokinesia;latent period;male;Mini Mental State Examination;motor dysfunction;multiinfarct dementia;neurologic disease;structured interview;tremor;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Gunther, P.;Villmann, T.;Hermann, W.",2011,,,0,0,
1708,Wilson's disease,"Wilson's disease is an autosomal recessive disorder of hepatic copper disposition caused by mutations in the gene ATP7B, located on chromosome 13. This gene encodes a P-type adenosine triphosphatase (ATPase), known as the Wilson ATPase, which functions within hepatocytes to move copper across intracellular membranes. The copper-transporting action directly supports production of the ferroxidase caeruloplasmin, in which copper is incorporated, as well as excretion of copper into bile. Consequently, in Wilson's disease, serum concentrations of copper are low and hepatic retention of copper develops, leading to liver injury. Wilson's disease can present as hepatic, neurological or psychiatric disease; clinical phenotypes are highly varied. Other organ systems may also be involved. Although the usual age range for clinical presentation is 5-45 years, younger children and older adults can also present with this disease. Clinical investigations include tests of liver function, cerebral imaging, serum caeruloplasmin and copper, basal 24-hour urinary copper measurement, and hepatic parenchymal copper concentration. Genetic diagnosis is complex but definitive, and best used for family studies. Treatment is usually very effective and consists of life-long administration of a chelator (D-penicillamine or trientine) or zinc in pharmacological doses. Liver transplantation is nearly always required for patients presenting with fulminant hepatic failure (coagulopathy, encephalopathy, massive intravascular haemolysis, renal failure, elevated aminotransferases, subnormal alkaline phosphatase) or for those whose liver disease is unresponsive to medical treatment. Liver cancer is extremely uncommon in patients with Wilson's disease, but screening may be appropriate for older patients. © 2011 Elsevier Ltd. All rights reserved.",atp7b;caeruloplasmin;cirrhosis;copper;hepatolenticular degeneration;movement disorders;Wilson ATPase;Wilson's disease;aggression;alanine aminotransferase blood level;alkaline phosphatase blood level;aplastic anemia/si [Side Effect];arthritis;article;aspartate aminotransferase blood level;autoimmune hepatitis;blood clotting disorder;bone marrow suppression/si [Side Effect];brain disease;cancer screening;ceruloplasmin blood level;chelation therapy;chromosome 13;copper blood level;decompensated liver cirrhosis;depression;diet supplementation;drug efficacy;dystonia;emotional stability;fatty liver;fulminant hepatic failure;gallstone;gastritis/si [Side Effect];gene mutation;heart arrhythmia;hemolysis;hepatomegaly;human;hypoparathyroidism;infertility;intravascular hemolysis;jaundice;kidney disease/si [Side Effect];kidney failure;liver biopsy;liver cancer/di [Diagnosis];liver cell;liver function test;liver transplantation;lupus vulgaris/si [Side Effect];memory disorder;neuroimaging;neurosis;pancreatitis;pathophysiology;priority journal;prognosis;protein losing nephropathy/si [Side Effect];seizure;skin disease/si [Side Effect];treatment response;tremor;unspecified side effect/si [Side Effect];vitamin supplementation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];adenosine triphosphatase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];alpha tocopherol;aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Roberts, E. A.",2011,October,http://dx.doi.org/10.1016/j.mpmed.2011.08.006,0,0,
1709,D-penicillamine induced elastosis perforans serpiginosa mimicking acne keloidalis nuchae,,acne;adult;case report;drug substitution;drug withdrawal;elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];histopathology;human;human tissue;laboratory test;letter;male;neck;papule/dt [Drug Therapy];papule/si [Side Effect];skin defect;skin examination;skin nodule/dt [Drug Therapy];skin nodule/si [Side Effect];staining;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Pavithra, S.;Rao, S.;Vishal, B.;Pai, G. S.",2011,July-August,http://dx.doi.org/10.4103/0019-5154.84730,0,0,
1710,Access to orphan drugs despite poor quality of clinical evidence,"AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French 'Haute Autorite de Sante', including the five-point scale parameter 'Service Medical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P= 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.","Clinical evidence;Orphan drug;Orphan medicinal product;Rare diseases;acromegaly/dt [Drug Therapy];acute lymphoblastic leukemia/dt [Drug Therapy];adrenal cortex carcinoma/dt [Drug Therapy];advanced cancer/dt [Drug Therapy];article;Belgium;chronic myeloid leukemia/dt [Drug Therapy];disease severity;drug cost;drug efficacy;drug exposure;drug legislation;enzyme replacement;evidence based medicine;Fabry disease/dt [Drug Therapy];gastrointestinal stromal tumor/dt [Drug Therapy];Gaucher disease/dt [Drug Therapy];glycogen storage disease type 2/dt [Drug Therapy];health care quality;human;hyperammonemia/dt [Drug Therapy];kidney carcinoma/dt [Drug Therapy];lymphoma/dt [Drug Therapy];mucopolysaccharidosis/dt [Drug Therapy];multiple myeloma/dt [Drug Therapy];national health insurance;priority journal;promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];reimbursement;thrombocytosis/dt [Drug Therapy];tyrosinemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase beta/ct [Clinical Trial];agalsidase beta/dt [Drug Therapy];anagrelide/ct [Clinical Trial];anagrelide/dt [Drug Therapy];arsenic trioxide/ct [Clinical Trial];arsenic trioxide/dt [Drug Therapy];bortezomib/cb [Drug Combination];bortezomib/dt [Drug Therapy];bosentan/dt [Drug Therapy];busulfan/iv [Intravenous Drug Administration];busulfan/po [Oral Drug Administration];busulfan/pe [Pharmacoeconomics];busulfan/pk [Pharmacokinetics];carglumic acid/dt [Drug Therapy];dasatinib/ct [Clinical Trial];dasatinib/dt [Drug Therapy];dexamethasone/cb [Drug Combination];dexamethasone/dt [Drug Therapy];ibuprofen/cm [Drug Comparison];iduronate 2 sulfatase/ct [Clinical Trial];iduronate 2 sulfatase/dt [Drug Therapy];indometacin/cm [Drug Comparison];laronidase/ct [Clinical Trial];laronidase/dt [Drug Therapy];lenalidomide/ct [Clinical Trial];lenalidomide/cb [Drug Combination];lenalidomide/dt [Drug Therapy];miglustat/ct [Clinical Trial];miglustat/dt [Drug Therapy];mitotane/dt [Drug Therapy];nelarabine/ct [Clinical Trial];nelarabine/dt [Drug Therapy];nitisinone/dt [Drug Therapy];pegvisomant/ct [Clinical Trial];pegvisomant/dt [Drug Therapy];penicillamine/cm [Drug Comparison];prostacyclin/dt [Drug Therapy];razoxane/ct [Clinical Trial];recombinant glucan 1,4 alpha glucosidase/dt [Drug Therapy];sildenafil/dt [Drug Therapy];sorafenib/ct [Clinical Trial];sorafenib/dt [Drug Therapy];sunitinib/ct [Clinical Trial];sunitinib/dt [Drug Therapy];unindexed drug;zinc acetate/cm [Drug Comparison];zinc acetate/dt [Drug Therapy]","Dupont, A. G.;Van Wilder, P. B.",2011,April,http://dx.doi.org/10.1111/j.1365-2125.2010.03877.x,0,0,
1711,Metals in neurodegenerative disease,,Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/et [Etiology];bovine spongiform encephalopathy/et [Etiology];chelation therapy;degenerative disease/et [Etiology];dementia;editorial;Friedreich ataxia;gene mutation;human;Menkes syndrome/et [Etiology];metal binding;nonhuman;oxidative stress;Parkinson disease/et [Etiology];priority journal;protein aggregation;variant Creutzfeldt Jakob disease/et [Etiology];Wilson disease/et [Etiology];alpha synuclein;aluminum;amyloid beta protein;amyloid precursor protein;copper;copper zinc superoxide dismutase;iron;manganese;metal;prion protein;zinc,"Brown, D. R.",2011,March,http://dx.doi.org/10.1039/c1mt90005f,0,0,
1712,Late diagnosed Wilson disease with hepatic and neurological manifestations,"A 50-year-old woman was referred to our hospital due to liver dysfunction and progressive neurological symptoms. She had previously been diagnosed with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) had effectively normalized her serum aminotransferase levels, however, she presented with loss of balance, dysarthria and difficulty in handwriting. Autoantibodies and hepatitis virus markers were negative. Serum ceruloplasmin and copper levels were noted to be 9mg/dL and 32mug/dL, respectively. The 24-h urinary copper excretion was 331.8mug/day. Kayser-Fleischer ring was demonstrated. Histological examination of the liver revealed inflammatory infiltrate and fibrosis, and the hepatic copper concentration was 444.4mug/g dry weight. We diagnosed her as having Wilson disease and started treatment with trientine. Immuohistochemistry for keratin 8 and p62 demonstrated Mallory-Denk bodies. Many of the p62-expressing cells were positive for 4-Hydroxy-2-nonenal (HNE). Few Ki-67-positive hepatocytes were present in the liver. Wilson disease is one of the causes of NASH and UDCA may be a supportive therapeutic agent for Wilson disease. Cell proliferation is suppressed under copper-loaded conditions and this phenomenon may be associated with the clinical course of Wilson disease. © 2011 The Japan Society of Hepatology.",Ki-67;Late-onset;Ursodeoxycholic acid;Wilson disease;adult;aminotransferase blood level;article;case report;clinical feature;female;histopathology;human;immunohistochemistry;laboratory test;liver failure;neurologic disease;nonalcoholic fatty liver/di [Diagnosis];priority journal;slit lamp;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin;copper;trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration],"Honma, Y.;Harada, M.;Sato, M.;Katsuki, Y.;Hiura, M.;Shibata, M.;Narita, R.;Harada, R.;Abe, S.;Tabaru, A.;Tajiri, N.;Shimajiri, S.",2011,March,http://dx.doi.org/10.1111/j.1872-034X.2010.00754.x,0,0,
1713,Wilson's disease in adult. [French],"Purpose: Wilson's disease (WD) is an inherited disorder of copper metabolism, characterized by the accumulation of copper in the body due to defective biliary copper excretion by hepatocytes. We report a series of 19 patients with WD. Patients and methods: This is a retrospective and descriptive case series of patients with WD followed in two hospitals of North East of France. Results: Eight men and 11 women were studied. Median follow-up time was 16 years, median age at diagnosis was 18 years (range: 5-71 years). Median age at first symptom was 16 years. In addition to four cases diagnosed by familial screening, clinical manifestations at diagnosis were fatigue (n= 5), jaundice (n= 5), bleeding (n= 1), abnormal movement disorders (n= 2) and fortuitous (n= 2). Cirrhosis was identified in 14 patients, neurological involvement occurred in seven patients and four patients presented with psychiatric disorders. d-penicillamine was the first treatment in 18 patients, discontinued for severe adverse events in seven patients. Trientine or zinc salts were then prescribed. Medical treatment was successful in 13 patients, but five patients underwent liver transplantation. Haemochromatosis was associated in one case, and one patient developed cholangiocarcinoma. Conclusion: WD is severe. Medical treatment allows disease control if it is correctly observed. Conversely, worsening with irreversible damage can occur if the treatment is discontinued. © 2010 Societenationale francaise de medecine interne (SNFMI).",Cirrhosis;D-penicillamine;Extrapyramidal syndrome;Hepatitis;Movement disorder;Wilson's disease;adolescent;adult;aged;article;bile duct carcinoma/co [Complication];bleeding;child;clinical article;clinical feature;descriptive research;disease association;drug efficacy;drug safety;drug withdrawal;family study;fatigue;female;France;hemochromatosis;human;jaundice;liver cirrhosis/di [Diagnosis];liver transplantation;male;mental disease;motor dysfunction;neurologic disease;onset age;preschool child;prescription;retrospective study;school child;screening test;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Mercier-Jacquier, M.;Bronowicki, J. P.;Raabe, J. J.;Jacquier, A.;Kaminsky, P.",2011,June,http://dx.doi.org/10.1016/j.revmed.2010.12.012,0,1,
1714,"Pathology, clinical features and treatments of congenital copper metabolic disorders - Focus on neurologic aspects","Genetic disorders of copper metabolism, including Menkes kinky hair disease (MD), occipital horn syndrome (OHS) and Wilson's disease (WD) are reviewed with a focus on the neurological aspects. MD and OHS are X-linked recessive disorders characterized by a copper deficiency. Typical features of MD, such as neurologic disturbances, connective tissue disorders and hair abnormalities, can be explained by the abnormally low activity of copper-dependent enzymes. The current standard-of-care for treatment of MD is parenteral administration of copper-histidine. When the treatment is initiated in newborn babies, neurologic degeneration can be prevented, but delayed treatment is considerably less effective. Moreover, copper-histidine treatment does not improve connective tissue disorders. Novel treatments targeting neurologic and connective tissue disorders need to be developed. OHS is the mildest form of MD and is characterized by connective tissue abnormalities. Although formal trials have not been conducted for OHS, OHS patients are typically treated in a similar manner to MD. WD is an autosomal recessive disorder characterized by the toxic effects of chronic exposure to high levels of copper. Although the hepatic and nervous systems are typically most severely affected, initial symptoms are variable, making an early diagnosis difficult. Because early treatments are often critical, especially in patients with neurologic disorders, medical education efforts for an early diagnosis should target primary care physicians. Chelating agents and zinc are effective for the treatment of WD, but neurologic symptoms become temporarily worse just after treatment with chelating agents. Neurologic worsening in patients treated with tetrathiomolybdate has been reported to be lower than rates of neurologic worsening when treating with other chelating agents. © 2010 The Japanese Society of Child Neurology.",atp7a;atp7b;Copper;Menkes disease;Neurologic diseases;Occipital horn syndrome;Wilson's disease;clinical feature;computer assisted tomography;copper metabolism;gene mutation;genetic disorder/di [Diagnosis];human;Menkes syndrome/di [Diagnosis];Menkes syndrome/dt [Drug Therapy];neurologic disease;nonhuman;nuclear magnetic resonance imaging;occipital horn disease/di [Diagnosis];review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];copper/dt [Drug Therapy];tetrathiomolybdic acid;zinc/dt [Drug Therapy],"Kodama, H.;Fujisawa, C.;Bhadhprasit, W.",2011,March,http://dx.doi.org/10.1016/j.braindev.2010.10.021,0,0,
1715,Ultraviolet derivatization of low-molecular-mass thiols for high performance liquid chromatography and capillary electrophoresis analysis,"Thiols play an important role in metabolic processes of all living creatures and their analytical control is very important in order to understand their physiological and pathological function. Among a variety of methods available to measure thiol concentrations, chemical derivatization utilizing a suitable labeling reagent followed by liquid chromatographic or electrophoretic separation is the most reliable means for sensitive and specific determination of thiol compounds in real world samples. Ultraviolet detection is, for its simplicity, commonly used technique in liquid chromatography and capillary electrophoresis, and consequently many ultraviolet derivatization reagents are in used. This review summarizes HPLC and CE ultraviolet derivatization based methods, including pre-analytical considerations, procedures for sample reduction, derivatization, and separation of the primary biological aminothiols - cysteine, homocysteine, cysteinylglycine and glutathione, and most important thiol-drugs in pharmaceutical formulations and biological samples. Cognizance of the biochemistry involved in the formation of the analytes is taken. © 2010 Elsevier B.V.",gamma-Glutamylcysteine;CE determination;Cysteine;Cysteinylglycine;Derivatization;Drug thiols;Glutathione;Homocysteine;HPLC determination;Ne{open}-homocysteinyllysine;autosomal recessive disorder/dt [Drug Therapy];capillary electrophoresis;cystinuria/dt [Drug Therapy];essential hypertension/dt [Drug Therapy];heavy metal poisoning/dt [Drug Therapy];hemorrhagic cystitis/dt [Drug Therapy];high performance liquid chromatography;human;hyperthyroidism/dt [Drug Therapy];liver disease/dt [Drug Therapy];priority journal;reduction;review;rheumatoid arthritis/dt [Drug Therapy];sample;scleroderma/dt [Drug Therapy];ultraviolet radiation;Wilson disease/dt [Drug Therapy];acetylcysteine;aminothiol;captopril/dt [Drug Therapy];cystamine;disulfide;halide;ifosfamide;mercaptopurine;mesna/dt [Drug Therapy];methylthiouracil;oxazaphosphorine;penicillamine/dt [Drug Therapy];propylthiouracil/dt [Drug Therapy];thiamazole/dt [Drug Therapy];thiol;tiopronin/dt [Drug Therapy],"Kusmierek, K.;Chwatko, G.;Glowacki, R.;Kubalczyk, P.;Bald, E.",2011,15 May,http://dx.doi.org/10.1016/j.jchromb.2010.10.035,0,0,
1716,Corpus callosum abnormalities in Wilson's disease,"Introduction: Wilson's disease (WD) with neurological presentation is associated with brain lesions classically localised in globus pallidus, putamen, thalamus, mesencephalon, pons and dentate nucleus. Lesions of corpus callosum (CC) have not been studied in a broad population of patients with WD. Objective: Evaluation of the frequency of CC lesions in patients with neurological symptoms related to WD. Method: The authors included all patients with neurological expression of WD, followed in the French national centre for WD who had a brain MRI between March 2006 and December 2008. The localisation of brain lesions was analysed and the frequency of lesions in CC evaluated. All patients were assessed using the Unified Wilson's Disease Rating Scale. For patients with abnormalities located in CC, a clinical dysconnexion syndrome was investigated. Results: Among 81 patients (45 men, mean age: 34.8 years, from 12 to 74 years) with neurological expression, 42% had white-matter lesions on fluid-attenuated inversion recovery MRI. 23.4% of patients presented CC lesions, limited to the posterior part (splenium). The severity of disability estimated by Unified Wilson's Disease Rating Scale was correlated with the presence of CC lesions on MRI. Conclusion: Abnormalities in CC are not unusual (23.4%). Together with lesions of basal ganglia, CC signal changes should suggest the diagnosis of WD.",adolescent;adult;aged;analytical parameters;article;brain damage/di [Diagnosis];brain region;child;clinical evaluation;clinical feature;controlled study;corpus callosum;correlation analysis;disability severity;disease association;female;human;image analysis;major clinical study;male;neurologic disease;nuclear magnetic resonance imaging;onset age;patient assessment;priority journal;school child;scoring system;white matter;Wilson disease;chelating agent;copper;zinc,"Trocello, J. M.;Guichard, J. P.;Leyendecker, A.;Pernon, M.;Chaine, P.;El Balkhi, S.;Poupon, J.;Chappuis, P.;Woimant, F.",2011,October,http://dx.doi.org/10.1136/jnnp.2009.204651,0,0,
1717,Galactorrhea with menstrual irregularity:Something other than a prolactinoma?,"We report the case of a 29-year-old female who presented with galactorrhea and irregular menstrual periods. Laboratory tests showed elevated levels of serum prolactin, raising the possibility of a prolactinoma. However, further evaluation revealed an unusual and unexpected cause for her illness. © 2011 Hellenic Society of Gastroenterology.",Galactorrhea;Hyperprolactinemia;Prolactinoma;Wilson's disease;adult;article;case report;clinical feature;disease classification;dose response;drug dose increase;echography;esophagus varices/di [Diagnosis];female;follow up;gastrointestinal endoscopy;human;hypertransaminasemia/di [Diagnosis];international normalized ratio;laboratory test;liver cirrhosis/co [Complication];liver cirrhosis/di [Diagnosis];liver cirrhosis/dt [Drug Therapy];menstrual irregularity;nuclear magnetic resonance imaging;pallor/di [Diagnosis];physical examination;portal vein;prolactinoma/di [Diagnosis];prothrombin time;slit lamp;splenomegaly/di [Diagnosis];stomach disease/di [Diagnosis];vein dilatation;Wilson disease;albumin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];globin/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];prolactin/ec [Endogenous Compound];thyrotropin/ec [Endogenous Compound],"Naha Asst.Prof, K.;Prabhu, M.",2011,,,0,0,
1718,Hepatitis: General principles,"* Hepatitis has many causes, and because management differs greatly, depending on the specific diagnosis, clinicians should perform an organized search to identify the responsible disease and initiate treatment. * Before assuming that elevated serum AST and ALT values are hepatic in origin, it is important to verify that serum creatine kinase and aldolase values are within the normal range. * An elevated prothrombin time despite administration of vitamin K and low serum albumin concentrations are the most useful indicators of impaired synthetic function of the liver. * Total serum protein concentration can be in the normal range in spite of a low albumin value when the gamma globulins are increased significantly and the ratio of albumin to gamma globulins is inverted. * Complications of hepatitis can present a medical emergency, as in the case of coagulopathy, esophageal bleeding, or acute encephalopathy. * Based on strong evidence, liver biopsy is the gold standard for the diagnosis of almost all liver diseases. (1) * Based on strong evidence, HAV vaccine is highly recommended for all children who have any chronic liver disease. (2) * Based on strong evidence, breastfeeding does not increase the risk of HBV transmission. (3) * Based on strong evidence, infants born to HCV-infected mothers should be screened by measuring serum anti-HCV antibody at 18 months of age. (4).",active immunization;acute brain disease/co [Complication];acute hepatitis/di [Diagnosis];acute hepatitis/et [Etiology];alanine aminotransferase blood level;albumin blood level;ascites/dt [Drug Therapy];aspartate aminotransferase blood level;autoimmune hepatitis/dt [Drug Therapy];autoimmune polyendocrinopathy candidiasis ectodermal dystrophy/dt [Drug Therapy];blood clotting disorder/co [Complication];brain disease/co [Complication];celiac disease/th [Therapy];chronic hepatitis/di [Diagnosis];chronic hepatitis/et [Etiology];chronic liver disease/dt [Drug Therapy];creatine kinase blood level;cystic fibrosis/dt [Drug Therapy];delta agent hepatitis/dt [Drug Therapy];drug withdrawal;echography;esophagus hemorrhage/co [Complication];esophagus varices;gluten free diet;hemangioma;hepatitis/dt [Drug Therapy];hepatitis/si [Side Effect];hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];human;laboratory test;ligation;liver biopsy;liver cirrhosis/co [Complication];liver cirrhosis/su [Surgery];liver cirrhosis/th [Therapy];liver failure/co [Complication];liver fibrosis;liver function;liver necrosis;liver transplantation;malnutrition/co [Complication];nonhuman;passive immunization;portal hypertension/co [Complication];protein blood level;pruritus/co [Complication];review;sclerotherapy;splenomegaly;virus hepatitis/dt [Drug Therapy];vitamin supplementation;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alpha interferon/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];azathioprine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];creatine kinase/ec [Endogenous Compound];fructose bisphosphate aldolase/ec [Endogenous Compound];furosemide/dt [Drug Therapy];gamma glutamyltransferase/ec [Endogenous Compound];ganciclovir/dt [Drug Therapy];hepatitis A vaccine/dt [Drug Therapy];hepatitis antibody;immunoglobulin/ec [Endogenous Compound];immunosuppressive agent/dt [Drug Therapy];interferon/dt [Drug Therapy];isoniazid/ae [Adverse Drug Reaction];lamivudine/dt [Drug Therapy];methyldopa/ae [Adverse Drug Reaction];norfloxacin/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];peginterferon/cb [Drug Combination];peginterferon/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prothrombin/ec [Endogenous Compound];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];serum albumin/ec [Endogenous Compound];spironolactone/dt [Drug Therapy];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];vitamin K group,"Clemente, M. G.;Schwarz, K.",2011,August,http://dx.doi.org/10.1542/pir.32-8-333,0,0,
1719,Primary EBV infection resulting in lymphoproliferative disease in a teenager with crohn disease,,adolescent;article;case report;Crohn disease/di [Diagnosis];Crohn disease/dt [Drug Therapy];disease association;drug withdrawal;Epstein Barr virus;female;human;immunosuppressive treatment;lymphoproliferative disease/co [Complication];nonhuman;priority journal;pyrexia idiopathica;risk factor;symptom;treatment outcome;virus infection/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];azathioprine/dt [Drug Therapy];infliximab/dt [Drug Therapy];mesalazine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];ursodeoxycholic acid/cb [Drug Combination];ursodeoxycholic acid/dt [Drug Therapy],"Gidrewicz, D.;Lehman, D.;Rabizadeh, S.;Majlessipour, F.;Dubinsky, M.",2011,January,http://dx.doi.org/10.1097/MPG.0b013e3181e80410,0,0,
1720,A clinical assessment of wilson disease in patients with concurrent liver disease,"Goals: To investigate variations in clinical epidemiology of Wilson disease in patients with concurrent liver disease and the effect of coexisting disease on current diagnostic algorithms. Background: Wilson disease is a rare disorder and few studies exist on diagnosis and natural history. Currently available tools have limited efficacy in complex patients, and the presence of coexisting diseases may further limit their use. More in-depth analyses of Wilson disease among complex patients with concurrent diseases will help improve algorithms for earlier diagnosis and treatment. STUDY: A retrospective cohort study using data from a large tertiary-care center to carry out a clinical assessment of Wilson disease among patients with coexisting liver disease. Results: Forty-two Wilson disease patients were identified; 9 had comorbid liver diseases. The average age of diagnosis was significantly older in patients with concurrent liver disease compared with those without underlying disease (49.1 y vs. 26.8 y, P<0.0001). Patients with concurrent liver disease had more evidence of cirrhosis at presentation (9/9, 100% vs. 15/33, 45.5%), and showed greater mortality (4/8, 50% vs. 4/29, 13.8%, P=0.0222). Without mutation analysis data, a definitive diagnosis of Wilson disease using Leipzig criteria was made in 44% of patients with concurrent liver diseases. Conclusions: Patients with concurrent liver diseases were diagnosed with Wilson disease at significantly older ages, presented with more liver cirrhosis, and showed greater mortality. Mutation analysis is crucial for definitive diagnosis among complex cohorts and those with intermediate Leipzig scores. Copyright © 2011 by Lippincott Williams & Wilkins.",genetic mutation analysis;hepatic copper concentration;Kayser-Fleischer rings;Leipzig criteria;adult;age distribution;algorithm;alkaline phosphatase blood level;article;autoimmune liver disease/su [Surgery];cardiogenic shock;cause of death;ceruloplasmin blood level;clinical article;clinical assessment;clinical feature;cohort analysis;comorbidity;controlled study;dementia;depression;diagnostic approach route;disease classification;female;genetic analysis;heart arrest;hemochromatosis/su [Surgery];hepatitis C/dt [Drug Therapy];hepatitis C/su [Surgery];human;insomnia;liver cell carcinoma;liver disease/su [Surgery];liver level;liver transplantation;male;medical error;memory disorder;mortality;multiple organ failure;mutational analysis;neuropsychiatry;overall survival;paranoia;priority journal;prognosis;respiratory failure;retrospective study;septic shock;tertiary health care;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];alkaline phosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Wong, R. J.;Gish, R.;Schilsky, M.;Frenette, C.",2011,March,http://dx.doi.org/10.1097/MCG.0b013e3181dffaa5,0,0,
1721,Recurrent bleeding and bulbar myasthenia-like symptoms as the initial presentation of Wilson's disease: A case report,"Wilson's disease, an autosomal recessive disorder of copper metabolism, is usually associated with hepatic or neuropsychiatric manifestations. This is to describe a case of Wilson's disease presenting with recurrent bleeding and bulbar myasthenia-like symptoms. A 12 year old Hindu girl presented initially with recurrent bleeding manifestations such as epistaxis, hematemesis and melaena and followed by swallowing difficulty with fatigability after 2 years. The bleeding was attributed to thrombocytopenia initially and the swallowing difficulty remained undiagnosed as tests for myasthenia gravis were negative. Four years later, the patient developed nasal intonation of the voice with fatigability followed by a decline in scholastic performance. The patient was evaluated in our institute and subtle extrapyramidal signs in the form of asymmetric appendicular dystonia and bradykinesia were noted. Clinical evaluation, laboratory and radiological investigations led to the diagnosis of Wilson's disease. The cause of bleeding was most likely a defect of platelet function. No other cause of her bulbar myasthenia-like symptoms was evident. This case illustrates that in all patients of Wilson's disease with bleeding, a platelet function defect needs also to be considered. In cases of bulbar myasthenia-like symptoms where the diagnosis is not clear, Wilson's disease should be considered in the differential diagnosis, if there is hepatosplenomegaly.",article;bleeding;blood analysis;bone marrow examination;bradykinesia;brain radiography;case report;child;clinical feature;cranial nerve;differential diagnosis;dysarthria;dysphagia;dystonia/dt [Drug Therapy];epistaxis;erythropoiesis;fatigue;female;gait disorder;hematemesis;hepatomegaly;human;idiopathic thrombocytopenic purpura/di [Diagnosis];megakaryopoiesis;melena;mild cognitive impairment;myasthenia like syndrome;neurologic examination;nuclear magnetic resonance imaging;physical examination;recurrent disease;school child;splenomegaly;thrombocytopenia;voice change;Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];clonazepam/cb [Drug Combination];clonazepam/dt [Drug Therapy];immunoglobulin/iv [Intravenous Drug Administration];steroid/po [Oral Drug Administration];trihexyphenidyl/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Prasun, N.;Bagchi, M.;Joseph, A.;Pal, S.;Ghosh, S.;Mukherjee, S.;Senapati, A. K.;Das, S. K.",2011,June,,0,0,
1722,Wilson's disease in Asia,"Wilson's disease is an autosomal recessive disorder of copper metabolism. The resultant accumulation of copper primarily damages the liver and brain, resulting in hepatic, neurological and psychiatric symptoms. There have been many recent studies advancing the understanding of Wilson's disease in Asia. There are indications that the incidence of Wilson's disease in parts of Asia may be relatively high. Many genetic studies have identified various hot spots in the ATP7B gene in a variety of the Asian populations. Screening of these hotspot mutations may thus be useful in confirming the diagnosis. Despite the advances in treatment, lack of familiarity by the health care profession resulting in late diagnosis, and poor access to treatment particularly among those from the developing economies remain areas of major concern.",absence of side effects/si [Side Effect];Asia;autosomal recessive disorder;chelation therapy;China;clinical feature;copper metabolism;diet restriction;drug hypersensitivity/si [Side Effect];drug response;electrophysiology;gene mutation;genetic screening;Hong Kong;human;incidence;India;Korea;laboratory diagnosis;liver transplantation;long term care;low drug dose;monotherapy;nuclear magnetic resonance imaging;pathogenesis;prevalence;review;Taiwan;treatment failure;treatment indication;unspecified side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/pc [Prevention];dimercaprol/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Zhang, Y.;Wu, Z. Y.",2011,June,,0,0,
1723,Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and alzheimers disease,"This article reviews recent evidence, much of which has been generated by my groups research programme, which has identified for the first time a previously unknown copper-overload state that is central to the pathogenesis of diabetic organ damage. This state causes tissue damage in the blood vessels, heart, kidneys, retina and nerves through copper-mediated oxidative stress. This author now considers this copper-overload state to provide an important new target for therapeutic intervention, the objective of which is to prevent or reverse the diabetic complications.Triethylenetetramine (TETA) has recently been identified as the first in a new class of anti-diabetic molecules through the original work reviewed here, thus providing a new use for this molecule, which was previously approved by the US FDA in 1985 as a second-line treatment for Wilsons disease. TETA acts as a highly selective divalent copper (CuII) chelator that prevents or reverses diabetic copper overload, thereby suppressing oxidative stress. TETA treatment of diabetic animals and patients has identified and quantified the interlinked defects in copper metabolism that characterize this systemic copper overload state. Copper overload in diabetes mellitus differs from that in Wilsons disease through differences in their respective causative molecular mechanisms, and resulting differences in tissue localization and behaviour of the excess copper.Elevated pathogenetic tissue binding of copper occurs in diabetes. It may well be mediated by advanced-glycation endproduct (AGE) modification of susceptible amino-acid residues in long-lived fibrous proteins, for example, connective tissue collagens in locations such as blood vessel walls. These AGE modifications can act as localized, fixed endogenous chelators that increase the chelatable-copper content of organs such as the heart and kidneys by binding excessive amounts of catalytically active CuII in specific vascular beds, thereby focusing the related copper-mediated oxidative stress in susceptible tissues.In this review, summarized evidence from our clinical studies in healthy volunteers and diabetic patients with left-ventricular hypertrophy, and from nonclinical models of diabetic cardiac, arterial, renal and neural disease is used to construct descriptions of the mechanisms by which TETA treatment prevents injury and regenerates damaged organs. Our recent phase II proof-of-principle studies in patients with type 2 diabetes and in nonclinical models of diabetes have helped to define the pathogenetic defects in copper regulation, and have shown that they are reversible by TETA. The drug tightly binds and extracts excess systemic CuII into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency, even after prolonged use. Its physicochemical properties, which are pivotal for its safety and efficacy, clearly differentiate it from all other clinically available transition metal chelators, including D-penicillamine, ammonium tetrathiomolybdate and clioquinol.The studies reviewed here show that TETA treatment is generally effective in preventing or reversing diabetic organ damage, and support its ongoing development as a new medicine for diabetes. Trientine (TETA dihydrochloride) has been used since the mid-1980s as a second-line treatment for Wilsons disease, and our recent clinical studies have reinforced the impression that it is likely to be safe for long-term use in patients with diabetes and related metabolic disorders. There is substantive evidence to support the view that diabetes shares many pathogenetic mechanisms with Alzheimers disease and vascular dementia. Indeed, the close epidemiological and molecular linkages between them point to Alzheimers diseasevascular dementia as a further therapeutic target where experimental pharmacotherapy with TETA could well find further clinical application. © 2011 Adis Data Information BV. All rights reserved.","Alzheimers disease;arteriosclerosis;Copper overload;diabetes;diabetic arteriopathy;diabetic nephropathy;diabetic neuropathy;diabetic retinopathy;experimental pharmacology;experimental therapeutics;heart failure;iron;organ regeneration;oxidative stress;randomized clinical trials;selective copper chelation;triethylenetetramine;zinc;acetylator phenotype;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];antioxidant activity;blood vessel wall;cardiovascular disease;chelation therapy;chemical modification;chronic toxicity;clinical trial (topic);connective tissue;copper chelation;copper deficiency;copper metabolism;coronary artery blood flow;crystal structure;degenerative disease;dementia/et [Etiology];diabetes mellitus/dt [Drug Therapy];diabetes mellitus/et [Etiology];diabetic angiopathy;diabetogenesis;disease association;drug absorption;drug clearance;drug dose escalation;drug metabolism;drug safety;drug structure;drug tolerability;heart disease;heart left ventricle hypertrophy;hematologic disease;homeostasis;human;insulin dependent diabetes mellitus/et [Etiology];intoxication;iron metabolism;metabolic disorder;metal binding;molecular dynamics;multiinfarct dementia;nerve degeneration;neuropathology;non insulin dependent diabetes mellitus/dt [Drug Therapy];non insulin dependent diabetes mellitus/et [Etiology];nonhuman;phase 1 clinical trial (topic);phase 2 clinical trial (topic);protein expression;proteinuria;proteomics;randomized controlled trial (topic);recommended drug dose;regulatory mechanism;review;streptozocin diabetes;tissue injury;Wilson disease/dt [Drug Therapy];zinc metabolism;3 deoxyglucosone/ec [Endogenous Compound];8 hydroxydeoxyguanosine/ec [Endogenous Compound];acyltransferase/ec [Endogenous Compound];adenosine triphosphatase/ec [Endogenous Compound];advanced glycation end product/ec [Endogenous Compound];amine oxidase (copper containing)/ec [Endogenous Compound];aquaporin 1/ec [Endogenous Compound];arylamine acetyltransferase/ec [Endogenous Compound];collagen type 1/ec [Endogenous Compound];collagen type 3/ec [Endogenous Compound];collagen type 4/ec [Endogenous Compound];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];drug metabolite;endothelium derived hyperpolarizing factor/ec [Endogenous Compound];extracellular superoxide dismutase/ec [Endogenous Compound];fibronectin/ec [Endogenous Compound];heparan sulfate/ec [Endogenous Compound];methylglyoxal/ec [Endogenous Compound];n1 acetyltriethylenetetramine;n1,n10 diacetyltriethylenetetramine;penicillamine/dt [Drug Therapy];placebo;plasminogen activator inhibitor 1/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];Smad4 protein/ec [Endogenous Compound];tetrathiomolybdate ammonium/dt [Drug Therapy];transforming growth factor beta1/ec [Endogenous Compound];trientine/ct [Clinical Trial];trientine/an [Drug Analysis];trientine/cr [Drug Concentration];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/iv [Intravenous Drug Administration];trientine/po [Oral Drug Administration];trientine/pk [Pharmacokinetics];trientine/pd [Pharmacology];unclassified drug;zinc/dt [Drug Therapy]","Cooper, G. J. S.",2011,,http://dx.doi.org/10.2165/11591370-000000000-00000,0,0,
1724,Mapping brain metals to evaluate therapies for neurodegenerative disease,"The brain is rich in metals and has a high metabolic rate, making it acutely vulnerable to the toxic effects of endogenously produced free radicals. The abundant metals, iron and copper, transfer single electrons as they cycle between their reduced (Fe<sup>2+</sup>, Cu<sup>1+</sup>) and oxidized (Fe<sup>3+</sup>, Cu<sup>2+</sup>) states making them powerful catalysts of reactive oxygen species (ROS) production. Even redox inert zinc, if present in excess, can trigger ROS production indirectly by altering mitochondrial function. While metal chelators seem to improve the clinical outcome of several neurodegenerative diseases, their mechanisms of action remain obscure and the effects of long-term use are largely unknown. Most chelators are not specific to a single metal and could alter the distribution of multiple metals in the brain, leading to unexpected consequences over the long-term. We show here how X-ray fluorescence will be a valuable tool to examine the effect of chelators on the distribution and amount of metals in the brain. © 2010 Blackwell Publishing Ltd.",Chelator;Copper;Iron;Metal;Neurodegeneration;Synchrotron;X-ray fluorescence;Zinc;Alzheimer disease/dt [Drug Therapy];brain mapping;chelation therapy;clinical assessment tool;clinical evaluation;degenerative disease;Friedreich ataxia;human;review;spectroscopy;Wilson disease/dt [Drug Therapy];X ray fluorescence;chelating agent;clioquinol/dt [Drug Therapy];deferoxamine;penicillamine/dt [Drug Therapy];reactive oxygen metabolite/ec [Endogenous Compound],"Gh Popescu, B. F.;Nichol, H.",2011,August,http://dx.doi.org/10.1111/j.1755-5949.2010.00149.x,0,0,
1725,Sleep disorders in Wilson's disease,"Background: Wilson's disease (WD) is an autosomal recessive inherited disease with copper accumulation; neurodegeneration is associated with dopaminergic deficit. The aim of the study is to verify sleep co-morbidity by questionnaire and objective sleep examinations (polysomnography, multiple sleep latency test).Methods: Fifty-five patients with WD (22 hepatic, 28 neurological, five asymptomatic form) and 55 age- and sex-matched control subjects completed a questionnaire concerning their sleep habits, sleep co-morbidity, Epworth sleepiness scale (ESS), and answered screening questions for rapid eye movement (REM) behaviour disorder (RBD-SQ). Twenty-four patients with WD and control subjects underwent polysomnographic examination.Results: Unlike the controls, patients with WD were more prone to daytime napping accompanied by tiredness and excessive daytime sleepiness, cataplexy-like episodes and poor nocturnal sleep. Their mean ESS as well as RBD-SQ was higher than that of the controls. Total sleep time was lower, accompanied by decreased sleep efficiency and increased wakefulness. Patients with WD had lower latency of stage 1 and stage 2 of non-rapid eye movement (NREM) sleep and less amount of NREM sleep stage 2. One-third of the patients with WD were found to have short or borderline multiple sleep latency test (MSLT) values independent of nocturnal pathology (sleep apnoea, periodic leg movements and/or restless leg syndrome).Conclusions: Patients with WD often suffer from sleep disturbances (regardless of the clinical form). The spectrum of sleep/wake symptoms raises the suspicion that altered REM sleep function may also be involved. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.",Cataplexy;Multiple sleep latency test;Polysomnography;Questionnaire study;Sleep co-morbidity;Sleepiness;Wilson's disease;adult;article;comorbidity;controlled study;depression;disease association;Epworth sleepiness scale;female;hallucination;human;insomnia;latent period;major clinical study;male;parasomnia;periodic limb movement disorder;priority journal;questionnaire;REM sleep;restless legs syndrome;sleep apnea syndrome;sleep disorder;sleep parameters;sleep pattern;vivid dream;Wilson disease/dt [Drug Therapy];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];zinc derivative/cm [Drug Comparison];zinc derivative/dt [Drug Therapy],"Nevsimalova, S.;Buskova, J.;Bruha, R.;Kemlink, D.;Sonka, K.;Vitek, L.;Marecek, Z.",2011,January,http://dx.doi.org/10.1111/j.1468-1331.2010.03106.x,0,0,
1726,Atypical CT scan findings in a case of Wilson's disease,"Wilson disease (WD) is an autosomal recessive disease of a membranebound copper-transporting ATPase. Clinical manifewstations are caused by deposition of copper on brain and liver causing different clinical manifestations and radiologic findings. We report a case with atypical finding on CT scan of brain which showed presence of bilateral symmetrical hypodensity at thalamo-capsular and frontal areas,not found commonly in WD along with minimal involvement of the lentiform nucleus. © E&C Hepatology.",Computed tomography;Hypodensity;Wilson's disease (WD);adolescent;article;autosomal recessive disorder;brain region;case report;clinical feature;computer assisted tomography;female;frontal cortex;human;thalamus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adenosine triphosphatase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Bhowmik, S.;Lahiri, S.",2011,,,0,0,
1727,Structural biology: A platform for copper pumps,,binding site;cell level;cell membrane transport;crystal structure;enzyme active site;enzyme activity;enzyme specificity;enzyme substrate;gene mutation;human;ion transport;Legionella pneumophila;Menkes syndrome/et [Etiology];nonhuman;note;priority journal;protein function;protein structure;transport kinetics;Wilson disease/et [Etiology];cadmium;cobalt;copper ion;lead;Menkes protein/ec [Endogenous Compound];metallochaperone/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc,"Robinson, N. J.",2011,07 Jul,http://dx.doi.org/10.1038/475041a,0,0,
1728,Molybdenum metabolism in the alga Chlamydomonas stands at the crossroad of those in Arabidopsis and humans,"Molybdenum (Mo) is a very scarce element whose function is fundamental in living beings within the active site of Mo-oxidoreductases, playing key roles in the metabolism of N, S, purines, hormone biosynthesis, transformation of drugs and xenobiotics, etc. In eukaryotes, each step from Mo acquisition until its incorporation into a biologically active molybdenum cofactor (Moco) together with the assembly of this Moco in Mo-enzymes is almost understood. The deficiency in function of a particular molybdoenzyme can be critical for the survival of the organism dependent on the pathway involved. However, incapacity in forming a functional Moco has a pleiotropic effect in the different processes involving this cofactor. A detailed overview of Mo metabolism: (a) specific transporters for molybdate, (b) the universal biosynthesis pathway for Moco from GTP, (c) Moco-carrier and Moco-binding proteins for Moco transfer and (d) Mo-enzymes, is analyzed in light of recent findings and three systems are compared, the unicellular microalga Chlamydomonas, the plant Arabidopsis and humans. © The Royal Society of Chemistry.",actin filament;adenylation;alga;amyotrophic lateral sclerosis;Arabidopsis;bacterium;biogenesis;biosynthesis;bovids;Caenorhabditis elegans;catalysis;cell membrane;cellular distribution;central nervous system;cerebellar ataxia;chemical stress;Chlamydomonas;Chlamydomonas reinhardtii;chloroplast;chromosome;crystal structure;cytoskeleton;disorders of porphyrin and heme metabolism;energy;environmental stress;enzyme mechanism;enzyme synthesis;Escherichia coli;eukaryote;fungus;gene overexpression;germination;glucose metabolism;human;hydrolysis;hydroxylation;hypoxia;liver cell;membrane channel;Menkes syndrome;metabolic disorder;metabolism;metal metabolism;mitochondrion;nitrogen deficiency;nonhuman;nucleotide sequence;open reading frame;oxidation;peroxisome;pH;photosynthesis;plant;priority journal;prokaryote;protein binding;protein degradation;protein expression;review;seed development;sideroblastic anemia;sulfation and desulfurization;upregulation;Wilson disease;ABC transporter;aldehyde oxidase;ATM protein;copper;cyclic GMP;cysteine;gephyrin;glycine;guanosine triphosphate;hydrogenase;mode protein;molybdenum;molybdenum cofactor;molybdic acid;nitrate reductase;peptides and proteins;protein moda;protein modb;protein modc;pyrophosphate;reactive oxygen metabolite;s adenosylmethionine;sulfite oxidase;tetramer;thiosulfate;trace element;unclassified drug;unindexed drug;xanthine dehydrogenase;xanthine oxidase;zinc,"Llamas, A.;Tejada-Jimenez, M.;Fernandez, E.;Galvan, A.",2011,June,http://dx.doi.org/10.1039/c1mt00032b,0,0,
1729,Is plasma exchange effective in prevention of hepatic transplantation in fulminant wilson disease with hepatic failure?,,abdominal pain;article;bleeding/dt [Drug Therapy];case report;ceruloplasmin blood level;child;Coombs test;copper blood level;diarrhea;erythrocyte concentrate;female;fulminant hepatic failure/th [Therapy];headache;hematocrit;hepatic coma/dt [Drug Therapy];human;international normalized ratio;jaundice;leukocyte count;liver transplantation;medical history;partial thromboplastin time;plasmapheresis;priority journal;reticulocyte count;school child;thrombocyte count;urea nitrogen blood level;urine level;vomiting;Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];gentamicin/dt [Drug Therapy];lactate dehydrogenase/ec [Endogenous Compound];lactulose/dt [Drug Therapy];penicillamine;protein/ec [Endogenous Compound];ranitidine/dt [Drug Therapy];trientine/dt [Drug Therapy];vitamin K group/dt [Drug Therapy];zinc/dt [Drug Therapy],"Akyldz, B. N.;Yldrm, S.;Kondolot, M.;Arslan, D.",2011,June,http://dx.doi.org/10.1097/MPG.0b013e318208d0a3,0,0,
1730,Mowat wilson syndrome; first case in Qatar identified by array comparative genomic hybridization (ACGH),"Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation syndrome usually associated with multiple health defects and characterized by typical facial gestalt. Approximately 200 cases have been reported worldwide predominantly in Europe and North America. The syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1) located on the long arm of chromosome 2 at 2q22. The spectrum of mutations includes point mutation (81%), intermediate and large mutations (17%) or large scale rearrangements (2%). We report the first case of MWS in Qatar. The 2 year old female patient has features of MWS. The array comparative genomic hybridization (aCGH) analysis was performed by 44k ISCA design oligonucleotide platform. The patient was found to have a de novo deletion of ~500kb at 2q22. The routine chromosome analysis was normal. The aCGH is a relatively new technology, which has revolutionized the field of clinical genetic diagnostics. The aCGH can detect unbalanced chromosomal aberrations including microdeletion, microduplication, aneuploidy, unbalanced translocations, and subtelomeric and pericentromeric copy number alterations throughout the genome. Unlike conventional cytogenetics, aCGH can detect deletions and duplications smaller than 5 megabases and, in contrast to single-color FISH, can scan for multiple aberrations simultaneously. This case emphasizes the value of array CGH to detect or characterize chromosome rearrangements in patients with mental retardation with/out dysmorphic features and multiple congenital anomalies.",Wilson disease;Qatar;comparative genomic hybridization;human;human genome;mutation;patient;Europe;gestalt therapy;female;point mutation;health;mental retardation malformation syndrome;chromosome 2;gene;mental deficiency;chromosome rearrangement;arm;homeobox;chromosome analysis;aneuploidy;chromosome aberration;diagnosis;technology;genome;cytogenetics;color;North America;congenital malformation;oligonucleotide;zinc finger protein,"Zafar, N.;Khitam, A. K.;Shabeer, P.;Mariam, A. M.;Rehab, A.;Tawfeg, B. O.;Amina, A. Z.",2011,,http://dx.doi.org/10.1007/s11568-011-9151-8,0,0,
1731,Treatment of patients with neurologic Wilson's disease,"Wilson's disease is an autosomal recessive disorder related to copper metabolism. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents and/or zinc. D-Penicillamine is considered to be the first drug of choice for Wilson disease patients in Japan. The chelating effect of this drug is excellent. However, 30 to 50 % of patients with neurologic symptoms may demonstrate a worsening of their symptoms in the early stages of treatment. Trientine is the second drug of choice in Japan. This agent has shown good results in response to the neurological symptoms of this disease. Zinc blocks intestinal copper absorption by inducing metallothionein synthesis in mucosal cells. Zinc is primarily used as a front-line therapy in pre-symptomatic patients with Wilson's disease. The author proposes a strategy of treatment for Wilson's disease patients with neurologic symptoms as follows: mild cases should treated by trientine mono-therapy, while moderate and severe cases require combination therapy with trientine and zinc.",patient;human;Wilson disease;neurologic disease;therapy;Japan;chelation;liver;monotherapy;tissues;synthesis;absorption;mucosa cell;copper metabolism;autosomal recessive disorder;zinc;copper;trientine;penicillamine;chelating agent;metallothionein,"Shimizu, N.",2011,October,,0,0,
1732,Zinc deficiency,"The essentiality of zinc for humans and its deficiency was recognized in 1963. During the past 50 years, it has become apparent that zinc deficiency is prevalent in humans. Nutritional deficiency of zinc may affect nearly 2 billion subjects in the developing world. Consumption of cereal proteins high in phytate decreases the availability of zinc for absorption. Conditioned deficiency of zinc is also very common. Growth retardation, hypogonadism in males, rough skin, impaired immunity, neurosensory disorder and cognitive impairment are some of the clinical manifestations of zinc deficiency. Zinc is involved in many biochemical functions. Over 300 enzymes require zinc for their activation and nearly 2000 transcription factors require zinc for control of gene expression. Zinc is also essential for cell mediated immunity. Zinc is an effective antioxidant and anti-inflammatory agent. In therapeutic dosages, zinc has been used for the treatment of acute diarrhea in infants and children, the common cold, Wilson's disease, sickle cell disease and for prevention of blindness in patients with age related macular degeneration.",zinc deficiency;human;cereal;immunity;male;child;hypogonadism;acute diarrhea;xeroderma;common cold;diseases;cognitive defect;gene expression;cellular immunity;absorption;nutritional deficiency;growth retardation;infant;sickle cell anemia;prevention;blindness;patient;age related macular degeneration;Wilson disease;zinc;phytate;antiinflammatory agent;enzyme;transcription factor;antioxidant;protein,"Prasad, A. S.",2011,October,,0,0,
1733,Zinc therapy for wilson's disease and alzheimer's disease,"Zinc is effective in all phases of Wilson's disease treatment and is the treatment of choice for maintenance therapy. It acts by blocking copper absorption at the intestinal level, and lacks the side effects of the other two anticopper drugs. Zinc is approved in the US, Europe, and Japan for Wilson's disease maintenance therapy. We will discuss appropriate dosing, monitoring and follow-up of zinc treated Wilson's disease patients. Because we discovered Alzheimer's disease (AD) patients were zinc deficient, and zinc is so important for neuronal functioning, we did a double blind clinical trial of a new once a day, gastroretentive, 150 mg zinc tablet developed by Adeona Pharmaceuticals, for 6 months in AD patients. Zinc treated patients over age 70 had statistically significant better scores than the placebo group in two cognition scoring systems (ADAS-Cog, p= 0.037 and CDR-SOB, p= 0.03), indicating zinc therapy has efficacy in older patients with AD.",therapy;Wilson disease;Alzheimer disease;human;patient;maintenance therapy;follow up;monitoring;absorption;cognition;scoring system;Japan;tablet;double blind procedure;Europe;side effect;zinc;placebo;copper,"Brewer, G. J.",2011,October,,0,0,
1734,The role of Sip1 in cranial neural crest development,"Smad interacting protein-1 (Sip1/Zeb2/Zfhx1b) is a highly conserved member of the two-handed zinc finger homeodomain family of transcriptional repressors which have been demonstrated to regulate the epithelial to mesenchymal transition (EMT) during tumor progression. Additionally, Sip1 is involved in neural and anterior-posterior patterning during embryonic development. Truncation of Sip1 proteins is also implicated in the neural crest-related disorders; Mowat-Wilson syndrome and Hirschprung disease. We have begun to investigate the spatiotemporal expression pattern and function of Sip1 in the neural crest during chicken embryonic development. Loss of function experiments were performed using translation blocking morpholino oligonucleotides, which were injected after the onset of neural development, to assess the role Sip1 during cranial neural crest development. With this approach we can determine whether Sip1 functions similarly in cancer cells and neural crest EMT and if it has any additional functions during embryonic development. Our results show that loss of Sip1 has no effect on cranial crest specification, but it prevents or delays migration of the crest out of the dorsal neural tube. Future studies will identify the mechanism by which Sip1 regulates the onset of migration in these cells.",neural crest;society;developmental biology;embryo development;epithelial mesenchymal transition;repressor gene;Wilson disease;cancer cell;neural tube;diseases;tumor growth;chicken;protein;morpholino oligonucleotide;zinc finger protein;synapsin I,"Rogers, C.;Bronner-Fraser, M.",2011,01 Aug,http://dx.doi.org/10.1016/j.ydbio.2011.05.416,0,0,
1735,Lingual dyskinesia and tics: A novel presentation of copper metabolism disorder,"Background: Abnormalities of copper metabolism were linked with neurological disorders affecting movement; however, their diagnosis is elusive, especially in cases with atypical characteristics. Methods: Case report. Results: A previously-healthy 16 year old male presented with acute onset of abnormal hemilingual wave-form movements, with his tongue deviating to the left in a twisted fashion. Movements were suppressed when patient was asked to extrude his tongue; they did not interfere with swallowing or speech, and did not persist during sleep. Upon examination sudden ballismic and tic-like movements of all limbs were noted, which could be suppressed voluntarily. Otherwise normal neurological evaluation. Extensive metabolic, hematologic and serologic investigations were normal. Serum ceruloplasmin and copper levels were low; 24-hour urine collection revealed normal copper excretion, but penicillamine challenge showed increased urinary copper. These increased values were higher than the norm, but still significantly lower than the diagnostic value for Wilson's disease. Brain MRI was normal. Screening for Wilson's and Huntington's disease was negative. Patient was started on zinc gluconate supplement. After 8 weeks the movements disappeared, although copper and ceruloplasmin levels were not normalized. Conclusions: This is the first case presenting association between copper metabolism disorders, tics and hemilingual dyskinesia in humans.",dyskinesia;tic;copper metabolism;metabolic disorder;tongue;human;patient;speech;excretion;swallowing;diagnosis;examination;case report;sleep;neurologic disease;male;ceruloplasmin blood level;urine;diagnostic value;brain;screening;limb;nuclear magnetic resonance imaging;Huntington chorea;Wilson disease;copper;gluconate zinc;ceruloplasmin;penicillamine,"Goez, H. R.;Jacob, F. D.;Yager, J.",2011,May,,0,0,
1736,A young woman presenting with acute fulminant hepatic failure and severe hemolysis,"LEARNING OBJECTIVES: 1. Recognize the key clinical features of WilsonaTMs disease including physical examination findings 2. Manage the treatment of acute fulminant hepatic failure from WilsonaTMs disease CASE INFORMATION: A 22-year-old female presents with 3 days of yellowish discoloration of her eyes and skin. She also noted that her urine was dark and her stools had been a light green color for 3 weeks, accompanied by mild abdominal discomfort. She had never consumed alcohol and took no prescribed or over the counter medications. She had no previous sexual contact and no significant family medical history. Of note, she had been told that she had ""abnormal liver function"" as per routine blood work done 8 months earlier. She was afebrile with normal hemodynamics. Jaundice with intensely icteric sclera, and mild right upper quadrant tenderness without appreciable hepatomegaly, were notable on exam. She was neurologically intact and stool guaiac was negative. Her initial labs included creatinine 1.5, hematocrit 20%, platelet 135, bilirubin 59, direct bilirubin 34, AST 195, ALT of 27, alkaline phosphatase 14, LDH 1588, albumin 3.1,and INR 3.3. Acetaminophen level was 30.5 (upper normal 30). Ophthalmologic exam with slit-lamp revealed gold-brown deposits at the level of descemetaTMs membrane. Her serum copper level was elevated at 220. While emergent plasma exchange using fresh frozen plasma replacement was initiated to ameliorate severe intravascular hemolysis and consequent acute renal failure (ARF), she was listed as status 1A for liver transplantation with a presumptive diagnosis of WilsonaTMs disease. On day 2, continuous renal replacement therapy was begun for worsening ARF (creatinine 2.4) which raised the MELD score from 39 to 48. The patient successfully underwent orthotopic liver transplantation on day 4 and was subsequently discharged home on day 18 of hospitalization. Liver histology under rhodanine stain revealed cirrhosis with occasional nodules in which all of the hepatocytes and scattered macrophages contained granular intracytoplasmic copper. IMPLICATIONS/DISCUSSION: Wilson's disease is a rare autosomal recessive disorder with mutations in the ATP7B gene which impairs the transport of copper from hepatocytes into bile, leading to copper accumulation in tissues including the liver, brain, kidneys, and cornea. The disease was first clinically described in 1912 by K. Wilson as progressive hepato-lenticular degeneration, reflecting that the primary manifestations of the disease relate to copper depositions in liver and lenticular nuclei of the brain. The hepatic presentation is highly variable, ranging from asymptomatic to acute fulminant liver failure. Approximately half of patients present without symptoms or with chronic liver disease. These patients typically have low ceruloplasmin levels and frequently (50%) have pathognomonic Kayser-Fleischer rings on slit lamp exam; they are typically managed as outpatients with chronic chelation and/or zinc therapy. However, fulminant hepatic presentations, more commonly in females than in males (4:1), occur in up to 25% of cases. Key clinical features include rapidly progressive renal tubular disease, coombs-negative acute intravascular hemolysis, and laboratory discordance manifest as only mildly elevated serum transaminases and alkaline phosphatase but extremely elevated bilirubin levels. Acute hepatocellular necrosis leads to the release of copper ions into the circulation with toxic oxidative effects on red cell metabolic pathways and consequent hemolysis, as well as renal failure. In cases of fulminant hepatic failure, acute plasma exchange is the preferred bridge to liver transplantation since it can rapidly remove relatively large amounts of copper and alleviate hemolysis and further renal damage. Due to the otherwise high mortality and transplant's curative potential, patients with fulminant hepatic failure due to Wilson's disease are appropriately afforded the highest category of priority for liver transplantation.",human;fulminant hepatic failure;hemolysis;society;internal medicine;female;liver transplantation;patient;clinical feature;liver cell;brain;plasmapheresis;intravascular hemolysis;liver;slit lamp;abdominal discomfort;feces;mortality;acute kidney failure;physical examination;hepatomegaly;copper blood level;sclera;jaundice;outpatient;color;Wilson disease;hemodynamics;chelation;membrane;liver necrosis;erythrocyte;kidney injury;transplantation;diagnosis;continuous renal replacement therapy;male;blood;urine;gene;autosomal recessive disorder;liver function;skin;macrophage;family history;thrombocyte;mutation;liver cirrhosis;bile;tissues;stain;kidney;cornea;degeneration;chronic liver disease;therapy;laboratory;aminotransferase blood level;liver histology;metabolism;kidney failure;hematocrit;hospitalization;eye;international normalized ratio;copper;bilirubin;alkaline phosphatase;creatinine;alcohol;guaiac;paracetamol;gold;fresh frozen plasma;albumin;bilirubin glucuronide;non prescription drug;ceruloplasmin;rhodanine;zinc;copper ion;lactate dehydrogenase,"Zahiruddin, A.;Leung, S.;LeFrancois, D.",2011,October,http://dx.doi.org/10.1007/s11606-011-1814-6,0,0,
1737,"Enhancement of oncolytic virus therapy by an angiogenesis inhibitor, ATN-224","Oncolytic viruses (OVs) are genetically modified viruses specifically designed to destroy cancerous cells only. Within the tumor microenviron-ment, the angiogenic and inflammatory responses following OV inoculation have significantly limited the efficacy of oncolytic herpes simplex virus (oHSV) in clinical trials. Physiological levels of copper support angiogenesis and can inhibit the replication of wild-type HSV. Here, we tested whether OV efficacy could be enhanced by ATN-224, a second-generation analog of ammonium tetrathiomolybdate (TM), a copper-chelating agent approved by the U.S. Food and Drug Administration for the treatment of Wilson's disease and currently under investigation as an antiangiogenic and antineoplastic agent in clinical trials. Under serum concentration of copper, both OV replication and glioma cell killing were significantly inhibited (P < 0.001). ATN-224 treatment rescued this copper-mediated inhibition of OV replication and cytotoxicity in vitro (P < 0.01). Antitumor efficacy was evaluated in vivo using two xenograft glioma models. First, mice implanted with subcutaneous U251T3 gliomas were treated with PBS, ATN-224, OV, or OV + ATN224 (n = 10). Average tumor size in the OV + ATN224 group was significantly smaller than in the group treated with OV alone (21.51 vs. 153.93 mm < P = 0.0383). Next, mice implanted with intracranial U87deltaEGFR gliomas were treated as previously described (n = 8). Kaplan-Meier analysis revealed greater mean survival duration in the OV + ATN224 group than in the group treated with OV alone (43.875 days vs. 24.000 days). To test for a biological explanation for this enhanced efficacy, we evaluated U251T3 tumors from OV-treated mice receiving ATN-224 or PBS cotreatment. Analysis revealed that ATN-224-treated tumors had significantly increased viral presence in vivo compared to PBS-treated tumors. This result was observed when OV was administered both intratumorally (P < 0.05) and intravenously. Therefore, the reduced tumor growth and increased survival previously shown in vivo might be associated with enhanced viral replication. Collectively, our results strongly suggest that the cotreatment of ATN-224 with OV can significantly improve the poor efficacy profile of conventional clinical oncolytic virotherapy.",oncolytic virotherapy;society;oncology;neoplasm;glioma;mouse;survival;clinical trial (topic);cell killing;virus;cytotoxicity;tumor growth;glioma cell;in vitro study;angiogenesis;xenograft;blood level;food and drug administration;United States;inoculation;model;tumor volume;Kaplan Meier method;wild type;inflammation;virus replication;Wilson disease;angiogenesis inhibitor;choline tetrathiomolybdate;copper;oncolytic virus;oncolytic herpes virus;antineoplastic agent;chelating agent;tetrathiomolybdate ammonium,"Pradarelli, J.;Yoo, J. Y.;Kaka, A.;Alvarez-Breckenridge, C.;Pan, Q.;Antonio Chiocca, E.;Teknos, T.;Kaur, B.",2011,November,http://dx.doi.org/10.1093/neuonc/nor158,0,0,
1738,Case Report: Catatonia as a presenting symptom of wilsons disease,"Introduction: Wilson's disease is an autosomal recessive disorder caused by mutations in the ATP7B gene. Clinical manifestations are caused by copper deposition in different parts of the body. Psychiatric symptoms (mood and psychotic) may be presenting symptoms in 25% patients with Wilson's disease. Case Description: A 19 year old male patient presented with refusal to eat, disturbed sleep, maintaining posture, excitement, echopraxia, perseveration, decreased self care, minimal speech, suspiciousness that people are against him and discuss about him for 2 months duration. There was no past or family h/o mental illness. On mental status examination, patient had decreased psychomotor activity with occasional excitement, negativism, posturing, ecoprexia, perseveration and delusion of reference and persecution. General physical examination and Systemic examination were normal. He was diagnosed as catatonic schizophrenia & treated with trifluperazine and 4 ECTs. On Subsequent follow up trifluperazine dose was increased, within 4 days he presented with severe EPS and catatonic symptoms. Bush-Francis Catatonia Rating Scale score was 30 on admission. Antipsychotics were stopped, there was slow improvement in his EPS, but catatonic symptoms persisted, Quetiapine which has a low propensity for EPS was started and ECTs were continued. As he was young boy and born of 2nd degree consanguinous marriage and was sensitive for EPS we thought in terms of Wilsons disease and investigated. Investigations: Routine investigations were normal and MRI Scan of brain didn't reveal any copper deposition in basal ganglia. 24 hours urinary copper excretion was 2165 mg/lt, serum ceruloplasmin of 45 u/lt and serum copper 160 mug/dl. Slit lamp examination of the eye and X-rays of the hand were within normal limits. After starting him on zinc 50mg tid and ECTs he showed significant improvement in symptoms and was discharged. Conclusion: Catatonia is rarely associated with Wilson's disease. Because effective treatment is available, it is important to make this diagnosis early.",case report;Wilson disease;Indian;medical society;catatonia;human;patient;male;examination;mental disease;excitement;speech;mood;self care;rating scale;follow up;boy;basal ganglion;body posture;sleep;catatonic schizophrenia;physical examination;gene;delusion;defense mechanism;psychosis;psychomotor activity;mutation;autosomal recessive disorder;consanguineous marriage;brain;mental health;excretion;ceruloplasmin blood level;copper blood level;X ray;eye;slit lamp;diagnosis;nuclear magnetic resonance imaging;copper;trifluoperazine;quetiapine;zinc,"Shetageri, V. N.;Bhogale, G. S.;Patil, N. M.;Nayak, R. B.;Chate, S. S.",2011,April,,0,0,
1739,Triethylenetetramine metabolism and its implication in cancer chemotherapy,"Triethylenetetramine (TETA), a copper II chelator and a polyamine analog traditionally used for the treatment of Wilson's disease, is currently in Phase I clinical trials for cancer in combination with carboplatin. However, the metabolism of TETA has never been thoroughly investigated, which is crucial for its further development in cancer treatment1. The two major metabolites of TETA found in humans are N<sup>1</sup>-acetyl-TETA (MAT) and N<sup>1</sup>,N<sup>10</sup>-diacetyl-TETA (DAT)<sup>2</sup>. Traditionally, acetylation of drug is thought to be catalyzed by N-acetyltransferase (NAT2). FDA requires that pharmacological properties of any drug metabolized via acetylation route have to be investigated in population with different NAT2 phenotype. However, our recent clinical study showed that there was no significant difference in pharmacokinetic and metabolites profiles of healthy volunteers with fast or slow NAT2 acetylation phenotype<sup>3</sup>. We therefore hypothesize that the enzyme responsible to TETA acetylation is spermidine/spermine acetyltransferase (SSAT). We carried out in vitro drug metabolism assays to pin-point the enzyme responsible for TETA metabolism. TETA (as substrate) and acetyl-coenzyme A were incubated with human liver microsome and cytosol from 7 individuals in the presence or absence of pentamidine or acetaminophen separately. The formation of MAT from TETA was detected and measured using our LC-MS method published previously<sup>2</sup>. Both liver microsome and cytosol could catalyze the biotransformation of TETA. There is a huge inter-individual difference in the rate of metabolism in microsome and cytosol (K<inf>m</inf> range 181 - 12,457 muM, V<inf>max</inf> range 110 - 3,068 pg/min/mg protein). Pentamidine, a specific inhibitor for SSAT, could inhibit the reaction and increase Km by over 30%. While acetaminophen, a specific inhibitor for NAT2, did not show any inhibition effect. Same experiments had been performed in rat liver microsome and cytosol, and similar results were obtained apart from the K<inf>m</inf> and V<inf>max</inf> values. Two other analogs of polyamine, diethylnorspermine and diethylspermine, all of which are under investigation for the treatment of cancer, were assayed as well, and similar results were obtained. The identification of SSAT, which has never been before considered to be a xenobiotic metabolizing enzyme, as the enzyme to catalyze the actylation of polyamine analogs, have a significant importance in the cancer combination chemotherapy. Finding SSAT (instead of NAT2) as the metabolic enzyme of TETA suggests that TETA may be an ideal candidate for cancer combination chemotherapy, as cancer drugs are rarely metabolized via this route; thus competition for drug metabolizing enzyme is less likely to occur. However, it seems that individuals do have different SSAT phenotypes, and this needs to be taken into account when using TETA as a chemotherapeutic agent.","metabolism;cancer research;cancer chemotherapy;human;neoplasm;cytosol;acetylation;liver microsome;phase 1 clinical trial;metabolite;phenotype;cancer combination chemotherapy;competition;Wilson disease;in vitro study;drug metabolism;assay;liver;population;clinical study;pharmacokinetics;normal human;biotransformation;microsome;rat;food and drug administration;trientine;enzyme;polyamine;acyltransferase;pentamidine;paracetamol;xenobiotic agent;drug metabolizing enzyme;acetyl coenzyme A;chelating agent;copper;antiinfective agent;carboplatin;2,3 butanedione;protein","Lu, J.;Li, M.;Tingle, M.;Xu, H.;Cooper, G. J. S.",2011,,http://dx.doi.org/10.1158/1538-7445.AM2011-2532,0,0,
1740,Abdominal pain and gastritis as the side effects of zinc therapy in children with wilson disease,"Objectives and Study: Zinc compounds are commonly used for treatment of Wilson disease and are regarded safe and well tolerated. However, occasionally patients report abdominal pain and nausea and require change of pharmacotherapy. Except for reporting abdominal pain these side effects were not investigated thoroughly. The aim of our study was to determine the prevalence and characterize side effects of zinc therapy in children with Wilson disease. Methods:We retrospectively analyzed a group of 37 patients (20 females, 17 males, aged mean 12 y (6'18y)) with confirmed diagnosis of Wilson disease (according to the Ferenci score and mutation analysis). They were treated with zinc sulphate for 83.3 (8'344) weeks [median (range)]. All patients' complaints were considered as the potential drug adverse reactions. Results: Side effects were observed in 12 children (9 females, 3 males, aged mean 10,7yrs) and all were of gastrointestinal origin: abdominal pain, nausea or vomiting. They occurred after 67.1 (8'344) wks on zinc sulphate therapy. Esophagogastroduodenoscopy (EGD) was performed in 4 patients with persistent and severe abdominal pain and it revealed gastritis with mucosal ulceration and negative H. pylori test in all subjects investigated. In 2 children symptoms resolved on proton pomp inhibitors, in other 2 cases additional conversion to penicillamine was necessary. 2 patients with abdominal pain did not give consent to EGD. In the remaining patients clinical improvement was observed after a change to zinc acetate (2 patients), D-penicillamine (4 patients) or introduction of the alternative zinc sulphate dosage scheme (2 patients). Conclusion: It seems that adverse reactions as abdominal pain, nausea and even gastritis are relatively common in patients treated with zinc sulphate. They may occur at the different stage of therapy. In selected patients EGD should be done to detect and treat inflammation of upper gastrointestinal tract. Discontinuation of zinc sulphate is often inevitable and conversion to penicillamine or zinc acetate may be a safer option for these patients.",human;Wilson disease;abdominal pain;society;child;side effect;therapy;gastritis;nutrition;gastroenterology;patient;nausea;male;female;adverse drug reaction;drug therapy;prevalence;diagnosis;mutation;vomiting;esophagogastroduodenoscopy;ulcer;pylorus;inflammation;upper gastrointestinal tract;zinc;zinc sulfate;penicillamine;zinc acetate;zinc derivative;proton,"Janowska, A.;Janczyk, W.;Dadalski, M.;Socha, P.",2011,June,http://dx.doi.org/10.1097/MPG.0b013e318224e326,0,0,
1741,Long-term zinc therapy in wilson disease children with mild liver disease,"Objectives and Study: Wilson disease (WD) is a disorder of copper metabolism. In the pediatric age most cases have a hepatic presentation: the percentage of WD children presenting with isolated elevated aminotransferases ranges from 14% to 88%. It is widely accepted that penicillamine is the first-choice therapy for children with liver disease while zinc is indicated in presymptomatic patients and as maintenance therapy. The optimal medical therapy in patients presenting with isolated elevated serum aminotransferases remains unestablished. This reflects the absence of an agreement on classification of WD patients with isolated hypertransaminasemia as presymptomatic cases, requiring zinc, or cases with hepatic onset, requiring chelating agents. The aim of our study was to evaluate the efficacy of exclusive zinc monotherapy inWDchildren with isolated hypertransaminasemia. Methods: All WD patients referred to our Department of Pediatrics for diagnostic investigation of elevated serum aminotransferases were analyzed. The diagnosis of WD was established in presence of at least 2 of the following features: a low ceruloplasmin level (<20 mg/dL), an increased basal urinary copper level (>100 mcg/24 hours), an increased urinary copper level after the penicillamine challenge test (PCT; >1575 mcg/24 hours), an increased liver copper level (>250mg/g of dry weight). Among 43 enrolled WD patients, 29 were treated with zinc for a median period of 12 years (range 3'25). Zinc was the initial therapy of choice in 12 cases. Normalization of serum ALT was the main parameter of treatment efficacy in this study. Compliance to therapy was evaluated on the basis of clinical history and serum and urine copper and zinc levels. Results: Among 17 (58%) children, treated with penicillamine as first choice, 4 (24%) normalized ALT within a median of 14 months (range, 4 to 48), and started maintenance therapy with zinc. The remaining 13 (76%) patients with persistent hyper-ALT during penicillamine switched to zinc; nine of these (70%) normalized ALT on zinc within a median period of 9.5 months (range, 5 to 151). Eleven (92%) of the 12 patients, given zinc alone as first choice, normalized ALT within a median period of 14 months (range, 2 to 46). The patient with persistent hyper-ALT on zinc showed a poor compliance to treatment. According to 24-hour urinary copper excretion (56+/-4 versus 37+/-2mg) at the end of follow-up, the efficacy in terms of decopperization was comparable in 2 groups. Conclusion: Although penicillamine therapy is generally used for the initial treatment of WD, the present study has showed that zinc monotherapy may be used, as first line therapy, in WD children with isolated hypertransaminasemia at presentation.",human;therapy;gastroenterology;child;Wilson disease;liver disease;nutrition;society;patient;serum;hypertransaminasemia;maintenance therapy;monotherapy;diagnosis;diseases;liver;dry weight;urine;provocation test;follow up;classification;copper metabolism;pediatrics;excretion;zinc;penicillamine;copper;aminotransferase;chelating agent;ceruloplasmin,"Ranucci, G.;Di Dato, F.;Della Corte, C.;Vajro, P.;Iorio, R.",2011,June,http://dx.doi.org/10.1097/MPG.0b013e318224e326,0,1,
1742,Wilson's disease: Treatment on integrated traditional Chinese medicinal herbs and western medicine,"Objective: To analyse the outcomes of patients with Wilson's disease, treated by simple western drugs integrating Traditional Chinese and Western medicine, and orthotropic liver transplantation (OLT). Background: Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive disorder of copper metabolism caused by ATP7B gene mutation. As WD is an inherited disease of the nervous system which is medicable, early diagnosis and early and life-long treatment lead to better prognoses. The best treatment recommended for Wilson's disease currently is to integrate traditional Chinese and Western medicines. See Wang X-P, etc. Neurology in the People's Republic of China - An Update. Eur Neurol 2010;64:320-324. Methods: Over 10,000 WD inpatients have been treated by neurologists in China in four WD centers (Hefei, Shanghai, Guangzhou and Chang- sha), and about 100 WD patients have been treated surgically by OLT. Results: The decision of whether to choose transplantation is complex and more than a purely medical judgment, and contradictions even occur across the varied WD centers, especially differences between physicians and surgeons. Generally within four years neuro- logically affected patients can improve while on medical therapy, showed that for years and even decades over 80% of treated WD patients live basically normal lives by integrated medical treatment. Conclusions: Treatment integrating traditional Chinese medicine and Western medicines: penicillamine and sodium dimercaptosuccinate have more significant effects on excretion of copper, and relatively more side effects. These characteristics make Western medicine more applicable to moderate to severe patients. Although the effect of Gan- dou Decoction is not as good as that of penicillamine or sodium Dimer- captosuccinateThese elements make traditional Chinese medicine especially suited for mild and moderate patients or for being taken in combination with Western medicine. Additionally, TCM herbs contained in Gandou Decoction are mostly rich in zinc. In this case, Gandou Decoction can be taken with Zinc preparation simultaneously, because they can reciprocally reinforce the effects on expulsion of copper. Hence, prior to choosing medication, we should obtain knowledge about the de-copperizing quantity of each kind of medicine and then select medicines with best effects and least side effects.",Wilson disease;herb;Parkinson disease;motor dysfunction;human;patient;Chinese medicine;China;therapy;side effect;drug therapy;autosomal recessive disorder;copper metabolism;gene mutation;nervous system;hospital patient;medical specialist;transplantation;decision making;physician;surgeon;excretion;liver transplantation;prognosis;neurology;early diagnosis;penicillamine;copper;zinc;dimer;succimer;valerian;sodium,"Wang, X. P.;Li, W.;Wang, J. F.",2011,May,http://dx.doi.org/10.1002/mds.23764,0,0,
1743,Wilson's disease: A Canadian perspective on the presentation and clinical outcomes in an adult ambulatory setting,"Objective: To review the clinical experience with Wilson's disease followed in a liver (LC) and movement disorders clinic (MDC) at a single centre in Toronto,Canada. Background: Wilson's disease (WD) is uncommon in Western countries. Long term follow-up and experience is therefore rare. Methods: A retrospective chart review of patients with a diagnosis of WD attending a LC and MDC. Results: Forty eight patients were included based on Leipzig criteria. The follow-up ranged from 0 - 26.8y in the LC and 0 - 19.8y in the MDC. Fourteen patients presented asymptomatically, 13 with hepatic symptoms, 15 with neurological symptoms, and 6 with dual hepatic/neurological symptoms. Median age at presentation was > 40y in 12.5%. Initial ceruloplasmin was low in 94% of cases, while 24h urinary copper was high in 95%. Neurological patients presented with a median of 4 symptoms (tremor, dysarthria and gait abnormalities were the commonest) while three patients developed neurological symptoms after diagnosis. Additional psychiatric symptoms were present in 26%. All neurologically presenting patients had KF rings. When MRI was performed abnormalities were reported in all patients with neurological symptoms but were normal in patients with pure liver symptoms or asymptomatic. Abnormalities included basal ganglia (62%) and brainstem (50%) lesions, atrophy (50%) and white matter changes (51%). D-penicillamine (D-P) was the most common initial therapy (48%) with zinc the most common at the time of review (65%). One patient had a successful liver transplant. Side effects were most prominent with D-P (41%). Neurological deterioration occurred in 11 subjects due to D-P or non-compliance but with 9 showing recovery. With neurological presentation, 14/21 had improved at time of review. Overall one death occurred. Conclusions: WD remains a diverse disease with generally favourable outcomes for those responding to initial therapy. However, evidence of compensated liver injury and structural brain damage are common and emphasize the need for close monitoring and therapy compliance with joint liver and movement disorder clinics.",Wilson disease;Parkinson disease;motor dysfunction;adult;human;patient;liver;neurologic disease;therapy;hospital;follow up;diagnosis;tremor;dysarthria;gait;mental disease;basal ganglion;brain stem;atrophy;white matter;nuclear magnetic resonance imaging;liver graft;side effect;deterioration;death;liver injury;brain damage;monitoring;medical record review;Canada;penicillamine;zinc;ceruloplasmin;copper,"Moores, A.;Hirschfield, G.;Lang, T.;Fox, S. H.",2011,May,http://dx.doi.org/10.1002/mds.23764,0,1,
1744,Gait disorder in a patient with Wilson's disease 18 years after onset of disease,"Objective: To describe the gait abnormalities in a patient who has been suffering from clinical signs of Wilson's disease for 18 years. Background: Wilson's disease is an autosomal recessive inherited disorder of copper metabolism leading to an excessive accumulation of copper in and outside the liver. A broad spectrum of neurological symptoms comprising dystonia, parkinsonian features, cerebellar and bulbar signs is very common and can severely impact the patient's quality of life. Even though gait disorder is a quite prominent neurological sign in Wilson's disease, the features of the gait abnormalities have not been described in detail in the literature. Methods: This 51-year-old male patient was diagnosed with Wilson's disease at the age of 33 after a 2 years lasting history of severe arm and head tremor resulting in a significant impairment of his working ability. Irritable and aggressive behavior was present at time of disease onset and worsened in the first years after the diagnosis. He reported a marked deterioration of symptoms after changing the treatment from D-penicillamine to zinc sulfate in the late 1990s. Even though D-penicillamine was reintroduced, since this time walking remained impaired and the patient has been bound to a walking frame to overcome his gait disorder in a suitable manner. Recent urine analysis showed that copper was effectively eliminated under D-penicillamine. Results: On neurological examination the patient showed a complex gait disorder comprising features of severe (gait-specific) dysto- nia as well as of gait apraxia and freezing of gait (FOG), respectively. While walking sidewards along the wall he used a simple cue to improve his gait impairment. Otherwise no significant impairment of leg motility and no marked dystonia could be observed when he was in a sitting or lying position. Some frontal signs were positive in this patient, pyramidal signs, however, were missing. Conclusions: This is an illustrative case showing a particular pattern of gait abnormalities with a combination of FOG and dystonia. While dystonia is well known in patients with Wilson's disease FOG is unusual and could reflect the involvement of different neuroana- tomical structures beyond the basal ganglia pathology.",human;patient;Parkinson disease;gait disorder;Wilson disease;motor dysfunction;gait;dystonia;walking;neurologic disease;male;arm;tremor;work capacity;diagnosis;deterioration;urinalysis;apraxia;aggression;freezing;leg;sitting;pyramidal sign;basal ganglion;pathology;autosomal recessive inheritance;copper metabolism;liver;bulbar paralysis;quality of life;neurologic examination;penicillamine;copper;zinc sulfate,"Brugger, F.;Felbecker, A.;Haegele-Link, S.;Tettenborn, B.;Kaegi, G.",2011,May,http://dx.doi.org/10.1002/mds.23764,0,0,
1745,Pallidal surgery for dystonia in Wilson's disease,"Objective: Wilson's disease is disease characterized by increased copper content in liver & brain. Surgical intervention has been limited in Wilson's disease as most symptoms potentially reverse with medical therapy. However, certain symptoms like disabling tremors are resistant to drug therapy and may require surgical intervention. Case report: A 20 year female patient with Wilson's disease since the age of four years, presented with jaundice. She was treated over the next nine years with penicillamine, trientine and zinc over various time intervals. At the age thirteen she worsened to develop tremor, with difficulty in writing. She was started on trihexyphenidyl, tetrabenazine and injectable botulinum toxin and her penicillamine dose was increased. At the age of fifteen years she was admitted as an emergency with unresponsiveness, hypotension, papilloedema, suspected hepatic encephalopathy. CSF revealed lymphocytic pleocy- tosis, high proteins, viral serology in serum CSF were negative, serum mycoplasma IgM was positive. She was treated with intravenous Acyclovir, Azithromycin, and pulsed with Methyl prednisolone, Dopa was added. Patient was on unable to eat or swallow. She was bedridden and unable to ambulate. [Video 1]. she was treated with high dose of penicillamine at 3gms /day over period of two years. She recovered partially and had significant residual dystonia, akinesia and rigidity. She was unable to speak clearly and was wheel chair bound. Her bradykinesia would respond to dopa replacement partially with worsening of dyskinesia of the mouth. [Video 2] She underwent DBS - Globus pallidal internus electrode placement with placement of IPG under general anaesthesia. Post surgery on serial follow ups her tone, mobility has improved, with minimal assistance in mobility. She is on tablet penicillamine 1500 mg per day with zinc[Video 3]. Conclusions: This young girl with Wilson's disease had persistent dystonia, parkinsonism, mutism causing significant disability despite adequate medical treatment and she thereafter improved with deep brain stimulation, (DBS) which has never been attempted in the past in dystonia due to Wilson's disease. Only a few case reports of surgery in Wilson's disease have been noted in the literature. The most common surgery was thalamotomy for resistant tremors.",Parkinson disease;Wilson disease;surgery;dystonia;motor dysfunction;videorecording;tremor;human;cerebrospinal fluid;therapy;serum;patient;female;case report;general anesthesia;tablet;girl;parkinsonism;mutism;brain depth stimulation;thalamotomy;liver;brain;drug therapy;jaundice;writing;emergency;hypotension;wheelchair;papilledema;hepatic encephalopathy;serology;Mycoplasma;swallow (bird);drug megadose;akinesia;rigidity;bradykinesia;dyskinesia;electrode;disability;penicillamine;zinc;copper;trientine;trihexyphenidyl;tetrabenazine;botulinum toxin;protein;immunoglobulin M;aciclovir;azithromycin;methylprednisolone,"Sankhla, C. S.;Chhabria, M.;Sankhe, M.;Udani, V.;Ravan, A.",2011,May,http://dx.doi.org/10.1002/mds.23764,0,0,
1746,Outcome and management of 207 pregnancies in Wilson disease,"Introduction: Wilson disease (WD) is a genetic copper storage disorder, leading to liver failure and neurological deterioration. Lifelong medical treatment is necessary to maintain copper homeostasis. Optimal treatment regimens in pregnant women are under debate in respect to abortion rate, teratogenicity and therapeutic efficacy. Aim: The current study aimed to assess outcomes of pregnancies in a retrospective multicenter cohort study Patients and methods: A total of 207 pregnancies in 100 WD patients in European tertiary care centers were analysed retrospectively. Medical regimens (D-penicillamine, Trientine, zinc salts, or a combination of a chelator and zinc) were classified and files were reviewed for maternal hepatic or neurological deterioration during pregnancy. Outcome of pregnancies and abortion rate were analyzed in respect to the maternal treatment and disease presentation. Results: Worsening of liver function tests was evident in 10 cases and occurred under all treatments to a similar extent. Liver function resolved after delivery in all cases. Neurologic deterioration in pregnancy was rare and was observed only in 2 cases (one under zinc, one under D-penicillamine therapy), but resulted in permanent worsening of the neurologic symptoms. Overall abortion rate was 48/207 (23.2%) in the study group. Of these, 46 abortions were recorded within the first three months; two still births were associated with placental insufficiency. Abortion rate under Trientine treatment (8/20; 40%; p=0.04) was higher than under D-penicillamine (14/96; 14.7%) or zinc (2/19; 10.5%). We observed inborn defects in 2/159 newborn: One child presented with partial oesophageal atresia (under D-penicillamine therapy of the mother), another child was diagnosed with a Glu-6-P-DH deficiency (under zinc therapy). Conclusion: In most cases control of liver function was maintained during pregnancy regardless of the chosen medical regimen. Neurologic deterioration was rare but resulted in severe disability in two cases. Thus, careful monitoring of WD patients during pregnancy is recommended. Contrary to previous reports we observed a higher rate of miscarriages under Trientine treatment. Potential teratogenicity remains a concern especially under D-penicilamine therapy.",pregnancy;liver;Wilson disease;liver disease;female;human;therapy;abortion;deterioration;patient;child;teratogenicity;liver function;disability;monitoring;spontaneous abortion;storage disease;liver failure;homeostasis;pregnant woman;cohort analysis;tertiary health care;maternal treatment;liver function test;placenta insufficiency;newborn;esophagus atresia;mother;neurologic disease;zinc;penicillamine;trientine;copper;zinc derivative;chelating agent,"Weiss, K. H.;Gotthardt, D.;Eckert, N.;Ferenci, P.;Stremmel, W.",2011,October,http://dx.doi.org/10.1002/hep.24666,0,1,
1747,An unexpected novel antioxidant-like activity for the classic copper-chelating drug penicillamine,"Penicillamine (beta, beta'-dimethylcysteine) has been widely used clinically as a copper-chelating drug for the treatment of copper overload in Wilson's disease. in this study, we found that penicillamine provided marked protection against cytotoxicity induced by tetrachlorohydroquinone (TCHQ), a major toxic metabolite of the widely used wood preservative pentachlorophenol, in human fibroblasts, while other classic copper chelating agents such as bathocuproine disulfonate do not. the autooxidation process of TCHQ yielding the reactive tetrachlorosemiquinone (TCSQ<sup>-</sup>) radical was studied by ESR and UV-visible spectral methods. We found, unexpectedly, the autooxidation process of TCHQ and the time course of TCSQ<sup>-</sup> radical formation was remarkably delayed by penicillamine in a concentration dependent manner. in contrast, no delaying effect on TCHQ autooxidation was observed by the classic copperchelating agent bathocuproine disulfonate. HPLC-MS and ESR studies showed that the TCSQ<sup>-</sup> radical was reduced to TCHQ by penicillamine, which was concurrently oxidized to its corresponding disulfide form. These data suggest that the protective effects of penicillamine on TCHQ-induced cytotoxicity were not due to its binding of copper, but rather to its reduction of the reactive TCSQ<sup>-</sup> radical to the much less reactive TCHQ. This is the first report demonstrating an unexpected novel antioxidantlike activity for this copper-chelating amino thiol drug, which might prove highly relevant to the biological activities of penicillamine.",society;autooxidation;cytotoxicity;protection;high performance liquid chromatography;human;fibroblast;biological activity;Wilson disease;penicillamine;copper;free radical;antioxidant;tetrachlorohydroquinone;toxin;wood protecting agent;pentachlorophenol;chelating agent;disulfide;thiol,"Zhu, B. Z.;Mao, L.",2011,01 Nov,http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.479,0,0,
1748,Triple liver transplantation for recurrent autoimmune hepatitis initially masquerading as fulminant wilson's disease,"In 2006, a 15 year-old female patient presented with symptoms of decompensated acute liver failure requiring listing for liver transplantation (LTx). Further lab tests were suggestive of Wilson's disease as serum levels of copper and caeruloplasmin were significantly reduced and copper excretion strongly increased upon penicillamin intake. Genetic analysis confirmed compound heterozygosity for Wilson's disease featuring two heterozygous mutations in exon 14 and 20 of the ATP7B gene, respectively. Further seemingly confirming the Wilson's diagnosis, the post-LTx histology was consistent with a decompensated course of Wilson's disease resulting in liver cirrhosis. Over the subsequent 28 months she developed numerous acute rejection episodes responsive to high-dose steroids but recurrent despite high-dose CNI- and mTOR-based immunosuppressive regimens, finally resulting in chronic allograft failure requiring listing for re-LTx. Upon re-LTx her clinical course was again characterized by recurrent rejection episodes resistant to conventional treatment regimens leading yet again to allograft failure with cirrhosis and the requirement for re-re-LTx by living donation from her mother 21 months after the second LTx. Before the third LTx she was pre-conditioned by plasmapheresis and Rituximab to prevent recurrence of allograft failure from a potentially antibodymediated damage. However, despite this and maximum immunosuppression including Alemtuzumab, photopheresis and plasmapheresis following re-re- LTx our patient again developed recurrent rejection episodes and signs of early-onset allograft failure and cirrhosis. Over her total clinical course, histologies of representative liver biopsies repeatedly showed cellular rejection infiltrates combined with signs of interface hepatits, cholangitis, lympho-plasmacytic infiltrates, and progressive fibrosis. Careful reevaluation of her case revealed that the Wilson's diagnosis was not quite accurate, rather the culprit was recurrent LKM-positive autoimmune hepatitis initially masqueraded by Wilson's disease. Subsequently, our patient was put on steroids and azathioprine with outcomes as yet to be determined.",Wilson disease;society;histocompatibility;liver transplantation;autoimmune hepatitis;organ transplantation;immunogenetics;human;allograft;liver cirrhosis;patient;plasmapheresis;female;diagnosis;histology;drug megadose;disease course;puva;liver biopsy;cholangitis;fibrosis;acute liver failure;blood level;excretion;genetic analysis;heterozygosity;mutation;exon;gene;acute graft rejection;mother;immunosuppressive treatment;copper;steroid;alemtuzumab;azathioprine;ceruloplasmin;penicillamine;rituximab,"Kroemer, A.;Doenecke, A.;Schnitzbauer, A.;Kirchner, G.;Farkas, S.;Loss, M.;Geissler, E. K.;Scherer, M.;Schlitt, H. J.",2011,September,http://dx.doi.org/10.1111/j.1432-2277.2011.01351.x,0,0,
1749,Ten Chinese paediatric patients with Wilsons disease,"Background: Wilson's disease (WD, MIM #277900) is an autosomal recessive disorder leading to systemic copper accumulation and multiorgan damage. For pediatric patients, hepatic manifestations predominate. Untreated WD causes progressive liver and neurological deterioration. Early treatment is the most effective way of preventing these serious outcome. Objective & Methods: We presented our experience of managing 10 paediatric WD patients. Data on clinical symptoms, laboratory findings, ultrasound findings, liver biopsies, genetic studies, treatment and outcome were studied. Results: Our patients were between 2 to 18 years of age at diagnosis. 1 patient presented in liver failure. 7 had abnormal liver functions detected incidentally. 2 were diagnosed through sibling screening. The most consistent abnormal liver function was an elevated alanine transaminase ranging from 60 to 419 IU/l (<58). Ceruloplasmin levels were all <0.1 g/l (0.21-0.59). Mean urinary copper excretion was 4 mumol/day (<1.0). 1 patient was treated initially with penicillamine and another trientine. 7 patients were started on zinc therapy. All remained well on follow up. Conclusion: Our patients represented a group of asymptomatic WD patients diagnosed and treated very early. With good treatment compliance, favourable outcome can be anticipated. One way of diagnosing these presymptomatic patients is through following up abnormal liver functions.",human;patient;metabolism;society;Wilson disease;liver function;therapy;follow up;patient compliance;autosomal recessive disorder;liver;deterioration;laboratory;ultrasound;diagnosis;liver failure;sibling;screening;excretion;liver biopsy;copper;trientine;zinc;alanine aminotransferase;ceruloplasmin;penicillamine,"Hui, J.;Chiang, G. P. K.;Yuen, Y. P.;Law, E. L. K.;Sun, K. K. M.;Tang, N. L. S.",2011,August,http://dx.doi.org/10.1007/s10545-011-9371-z,0,1,
1750,Hypersomnia in Wilson's disease,"Background and significance: Wilson's disease (WD) shows a wide heterogeneity in symptoms. In this case report we present hypersomnia as an unusual symptom in an unusual case of WD. Case: A 48-year-old woman was admitted because of cognitive impairment for 2 years. Her complaints as fatigue, decreased level of concentration, and depression started at 3 years ago. There was no family history of psychiatric or other neurologic illness. No abnormality was found at neurologic examination. A moderate elevation in liver function tests was found, but the viral hepatitis markers were negative. The diagnosis of WD was based on decreased ceruloplasmin level, increased urinary excretion of copper, and decreased level of serum copper. Kayser-Fleischer ring was not detectable. Brain MRI disclosed increase T1 signal lesions in both globus pallidus. Electroencephalography showed diffuse slow waves of bilateral hemisphere without epileptiform discharge. Liver biopsy showed the presence of nuclear glycogen a cytoplasmic brownish pigment in hepatocytes and a minimal degree of periportal fibrosis. At 8-10 months after the initiation of the D-penicillamine therapy her complaints gradually resolved. In one year since resolution, she became drowsier and more hypersomnolent. She spent more than 2/3 of the day sleeping. After the administration of Methylphenidate 20mg, she became almost alert and gradually improved negativism. Conclusions or comments: Hypersomnia was the main symptom in this patient. Although neurologic presentation of WD without Kayser-Fleischer rings have been already reported, lack of Kayser-Fleischer rings and the unusual clinical symptom demonstrate that this patint is a highly exceptional WD-patient.",hypersomnia;Wilson disease;Parkinson disease;human;patient;virus hepatitis;diagnosis;urinary excretion;brain;globus pallidus;electroencephalography;copper blood level;hemisphere;epileptic discharge;liver biopsy;liver cell;liver fibrosis;therapy;sleep;defense mechanism;case report;female;nuclear magnetic resonance imaging;fatigue;family history;general aspects of disease;neurologic examination;liver function test;cognitive defect;marker;ceruloplasmin;copper;glycogen;pigment;penicillamine;methylphenidate,"Kim, S.",2011,,http://dx.doi.org/10.1159/000327701,0,0,
1751,Wilson's disease presenting with the episodic hypersomnia,"Case: A 48-year-old woman was admitted because of fluctuating cognitive impairment for 2 years. Her complaints as fatigue, decreased level of concentration, and depression started at 3 years ago. She developed behavioral changes, emotional lability, restlessness and agitation. There was no specific family history. No abnormality was found at physical and neurologic examination. A moderate elevation in liver function tests was found, but the all viral hepatitis markers and VDRL were negative. Neither toxic nor infectious disease was detectable. The initial diagnosis of WD was based on decreased ceruloplasmin level, increased urinary copper excretion, and decreased serum copper. Kayser-Fleischer (KF) ring was not detected. Brain MRI disclosed increase T1 signal in both globus pallidus. EEG showed diffuse slow waves without epileptiform discharge. Liver biopsy was performed at 3 years after symptoms onset and showed the presence of nuclear glycogen with cytoplasmic brownish pigment in hepatocytes and a minimal degree of periportal fibrosis, but no sign of hepatitis or other liver disease was detectable. EM changes included mitochondrial swelling and crista defragmentation. No evidence of hepatic encephalopathy was found. Blood ammonia level was normal. At 8-10 months after the initiation of the D-penicillamine therapy her complaints gradually resolved. In one year since resolution, she became drowsier and more hypersomnolent episodically. During these attacks she spent more than 2/3 of the day sleeping. After the administration of methylphenidate, she became alert and gradually improved negativism. Conclusions: We present the Wilson's disease (WD) case with the episodic hypersomnia as the only symptom.",hypersomnia;Parkinson disease;Wilson disease;fatigue;mental instability;behavior change;agitation;restlessness;neurologic examination;family history;liver function test;virus hepatitis;infection;diagnosis;excretion;brain;copper blood level;epileptic discharge;globus pallidus;liver biopsy;liver cell;liver fibrosis;hepatitis;mitochondrion swelling;liver disease;hepatic encephalopathy;ammonia blood level;sleep;therapy;defense mechanism;electroencephalogram;human;cognitive defect;female;nuclear magnetic resonance imaging;marker;ceruloplasmin;copper;pigment;glycogen;penicillamine;methylphenidate,"Kim, S. Y.;Chang, Y.;Jang, I. M.;Eah, K. Y.",2011,,http://dx.doi.org/10.1159/000327701,0,0,
1752,IPS technology and it's implications for gene and cell therapy,"The generation of induced pluripotent stem cells (iPSCs) from somatic cells by exogenous factors opens a new era of possibilities for regenerative medicine. Potentially, once safety concerns are overcome differentiated lineages derived from patient specific iPSCs could be used for transplantation purposes and this would change the way we perceive medicine nowadays. However, for patients with genetic diseases the mutation will need to be corrected as otherwise the functional defect will remain. And the same can be said for other acquired diseases as well in which viruses can access cells through a specific receptor, for instance AIDS. To overcome these issues there is growing interest in applying zinc finger technology for either correcting mutations or knocking out genes. But this technology has limitations and is lengthy. In this regard, gene therapy of iPSCs or their differentiated progeny using clinically approved vectors could be a valuable possibility. Here we described the generation of iPSCs from a Chinese patient with Wilson's disease that bears the R778L Chinese hotspot mutation in the ATP7B gene, whose product is a liver enzyme responsible for copper export into bile and blood. These iPSCs were pluripotent and could be readily differentiated into functional hepatocytes that display abnormal cytoplasmic localization of mutated ATP7B and defective copper transport. Importantly, gene correction using a self-inactivating lentiviral vector that expresses codon optimized-ATP7B could reverse the functional defect. In the future, hepatocytes from similarly genetically corrected iPSCs may also be an option for autologous transplantation in Wilson's disease. Notably, we also provide proof of principle that our experimental model based on iPSCs can be used to screen compounds aimed to correct the abnormality.",gene;technology;society;cell therapy;mutation;patient;liver cell;Wilson disease;somatic cell;regenerative medicine;safety;transplantation;genetic disorder;virus;acquired immune deficiency syndrome;gene therapy;progeny;bile;blood;codon;experimental model;pluripotent stem cell;autotransplantation;copper;receptor;zinc finger protein;liver enzyme;lentivirus vector,"Pei, D.",2011,May,http://dx.doi.org/10.1038/mt.2011.85,0,0,
1753,Zinc therapy in neurological Wilson's disease during pregnancy: Case report and review of the literature,"Objective: To report our experience in the management of zinc therapy during pregnancy in a patient affected by neurological Wilson's disease, in parallel with a review of the literature concerning this issue. Methods: We treated a patient affected by neurological Wilson's disease with decreased zinc doses during pregnancy, because of her scarce compliance to a full-dosage while being in this condition. Throughout pregnancy, the patient underwent bi-monthly clinical and laboratory evaluations including an extensive assessment of copper balance. Results: Urinary copper excretion and serum zinc levels were below the proposed effective therapeutic ranges in all determinations. However, serum free-copper levels were always within therapeutic ranges, and both liver and neurological functions were quite stable throughout the course of the pregnancy, confirming a good compliance to the reduced therapeutic schedule and supporting its efficacy. Fetal development, periodically monitored by ultrasound studies, resulted normal and finally the patient delivered a full-term, healthy baby. Conclusions: In agreement with the literature, we confirm that zinc therapy is safe and effective during pregnancy. Moreover our data provide further evidence that serum ""free copper"" levels would be more sensitive than urinary copper excretion for monitoring compliance to zinc therapy and evaluating the efficacy of such treatment.",case report;pregnancy;therapy;Wilson disease;society;patient;serum;excretion;fetus development;ultrasound;baby;monitoring;copper metabolism;zinc blood level;laboratory;liver;zinc;copper,"Bianchi, M. L.;Masciullo, M.;Modoni, A.;De Carolis, S.;Silvestri, G.",2011,May,http://dx.doi.org/10.1007/s00415-011-6026-9,0,0,
1754,Wilson's disease,"Wilson's disease (WD) is a rare inborn autosomal recessive disorder of copper metabolism secondary to ATP7B gene mutations. This gene encodes an ATPase protein, which is responsible for the billiard copper excretion. This results in copper accumulation in the liver and later on in other organs, such as the brain. Since the first reports in the 1990s more than 400 mutations have been identified in diverse populations around the world. Neurological manifestations, appearing in the second or third decade, are the initial presentation in about half the patients and can be highly variable. The majority of cases have a neurological clinical picture with a wide range of combinations of dysarthria, tremor, gait disorders, dystonia, and parkinsonism. The diagnosis of WD may be suspected in all patients with chronic progressive movement disorder of unknown etiology, mainly if onset is in the second or third decade of life. The accurate, prompt diagnosis of individuals with WD is important since early treatment, halts disease progression and may reverse established liver and brain damage to some degree. The diagnosis first step for the diagnosis of WD is a sensible clinical suspicion. No single test is definitive and here is no universally accepted biochemical ""gold standard"". The diagnosis is based on the clinical picture and the combination of the results of several tests. The main diagnostic procedures in WD are: slit-lamp examination, serum ceruloplasmin level, urinary copper excretion (UCE), penicillamine challenge UCE, hepatic copper concentration, MR Imaging and genetic test to detect ATP7B gene mutations. In this presentation diagnostic criteria in Wilson's disease will be discussed. The aim of pharmacological treatment of Wilson0s disease is to restore the copper balance. The main drugs employed are chelating agents as d-penicillamine and trientine or zinc salts to limit gastrointestinal absorption of copper. Orthotopic liver transplantation is indicated for patients with fulminant hepatic failure and for those with chronic, severe hepatic insufficiency that do not respond to pharmacological therapy.",Wilson disease;society;diagnosis;patient;drug therapy;gene mutation;excretion;liver;copper metabolism;fulminant hepatic failure;liver failure;autosomal recessive disorder;brain;gene;population;dysarthria;tremor;gait disorder;dystonia;parkinsonism;mutation;etiology;disease course;motor dysfunction;diagnostic procedure;slit lamp;ceruloplasmin blood level;nuclear magnetic resonance imaging;gold standard;gastrointestinal absorption;liver transplantation;brain damage;copper;penicillamine;adenosine triphosphatase;protein;chelating agent;trientine;zinc derivative,"Barbosa, E. R.",2011,May,http://dx.doi.org/10.1007/s00415-011-6026-9,0,0,
1755,Efficacy and safety of D-penicillamine and trientine for the treatment of wilson disease,"Introduction: Wilson disease (WD) is a genetic copper storage disorder, leading to liver failure and neurological deterioration. Current guidelines favour the use of chelating agents (dpenicillamine, trientine) in first line therapy of symptomatic patients but optimal regimens still have to be established. Clinical data on larger cohorts comparing these chelators are limited. Aim: The current study aimed to assess long-term outcomes of d-penicillamine and trientine in a retrospective multicenter cohort study. Patients and Methods: A total of 350 WD patients in European tertiary care centers and patients contributed by the EUROWILSON database research group were analysed retrospectively. Chelator based medical regimens were analysed for efficacy, adverse events and reasons for discontinuation using Kaplan-Meier-estimation. Treatments with duration of less than 6 months were censored. Results: Hepatic and neuropsychiatric symptoms were present in 221 (63.1%) and in 119 (34%) patients, respectively. Patients were treated initially with d-penicillamine (n = 309) or trientine (n = 41). Changes of medication were common in both groups, resulting in a total of 514 analysed treatments (d-penicillamine n = 350, trientine n = 164). Actuarial survival free of transplantation (median follow-up: 16.5 years) was similar (death: d-penicillamine n = 7/350, trientine n = 3/164; progression to liver transplantation: d-penicillamine 12/350, trientine 2/164). In the d-penicillamine group, adverse events leading to discontinuation of treatment were more frequent (p = 0.045) and occurred even after decades of therapy. For the latest available time point of a 48 months follow-up, hepatic deterioration occurred only in 8/514 treatments (d-penicillamine n = 3, trientine n = 5, p = n.s.). However, neurologic deterioration was less frequent in the d-penicillamine group (7/350 treatments) compared to trientine (12/164, p = 0.005) while improvement of symptomatic neurologic patients was recorded to a similar extent (d-penicillamine 84/139; trientine 42/79, p = n.s.). Interestingly, hepatic improvement of symptomatic patients was more often observed for d-penicillamine (211/235) than for trientine (64/86, p < 0.05). Conclusion: In the majority of patients treatment with chelating agents was effective, leading to a comparable and favourable actuarial survival free of transplantation. The main limitation in d-penicillamine treatment was the higher rate of adverse events. Neurological deterioration under chelation therapy was rare and contrary to our expectation more frequent in patients treated with trientine.",safety;Wilson disease;liver;patient;deterioration;transplantation;follow up;therapy;survival;storage disease;liver failure;clinical study;cohort analysis;tertiary health care;data base;Kaplan Meier method;drug therapy;death;liver transplantation;chelation therapy;trientine;penicillamine;chelating agent;copper,"Weiss, K. H.;Schots, M.;Gotthardt, D. N.;Ferenci-Foerster, D.;Maieron, A.;Stauber, R.;Reuner, U.;Houwen, R. H. J.;Stremmel, W.;Ferenci, P.",2011,March,http://dx.doi.org/10.1016/S0168-8278%2811%2900096-1,0,1,
1756,Wilson's disease with coexisting autoimmune hepatitis. A case report,"Wilson's disease [WD} - an inherited disorder of copper metabolism in individuals with mutant ATP7B genes, occurs in every ethnic and geographic population, with worldwide prevalence of about 30 in million. WD can present clinically as liver disease, as a progressive neurological disorder or as psychiatric illness. The spectrum of liver disease encountered in patients with WD can be highly variable, ranging from asymptomatic with only biochemical abnormalities to acute liver failure. Because at present de novo genetic diagnosis is expensive and not universally available,a combination of clinical findings and biochemical testing is usually necessary to establish the diagnosis if WD. We describe 19 year old female, who presented with classical features WD and several features of autoimmune hepatitis (AIH). The patient was initially diagnosed as having AIH and treated with standard corticosteroid therapy [prednisolone 60 mg daily] with caused, initial clinical improvement, but subsequent deterioration. The diagnosis of WD was made 4 moons after initial diagnosis of AIH. Subsequent diagnosis of WD and introduction of penicillamine [1 g daily] gave excellent improvement and normalization of liver function tests. We suppose that in this case concurrent WD and AIH cannot be excluded. Thus, in patients with AIH, a thorough screening for WD is necessary, particularly when the response to steroid therapy is poor. Conversely, in patients suffering from WD with superimposed features of AIH, a combination of steroids and penicillamine may be of benefit.",Wilson disease;liver;autoimmune hepatitis;case report;Asian;diagnosis;patient;liver disease;gene;population;prevalence;neurologic disease;mental disease;liver failure;corticosteroid therapy;deterioration;moon;liver function test;screening;steroid therapy;copper metabolism;mutant;female;penicillamine;prednisolone;steroid,"Vashakidze, E.;Gegeshidze, T.;Buachidze, T.",2011,March,http://dx.doi.org/10.1007/s12072-010-9241-z,0,0,
1757,"Pegylated interferon, ribavirin combination is associated with serious psychiatric manifestation in HCV patient with wilson disease, a case report","Chronic infection with the hepatitis C virus (HCV) is a common and growing problem. Neuropsychiatric symptoms are commonly associated with chronic HCV infection, its sequelae, and its treatment. In particular, interferon, a primary component of treatment for chronic hepatitis C and well known to be associated with significant adverse effects as depressive symptoms. Case report: We report a 24-year-old female who developed psychiatric symptoms after the second pegylated interferon dose and ribavirin for treatment of chronic hepatitis C infection, genotype 4. Therapy was promptly discontinued. Correction of possible etiological factors did not improve the condition. Wilson disease was found to be the undiagnosed etiological factor for these psychiatric manifestations, and was presented for the first time. D- Penicillamine treatment started with marvelous response. Recommendation: Consideration for a possible etiology for psychiatric manifestations during Interferon therapy is advisable.",case report;Wilson disease;patient;liver;Asian;etiology;infection;hepatitis C;therapy;adverse drug reaction;depression;female;Hepatitis C virus;mental disease;genotype;peginterferon;ribavirin;interferon;penicillamine,"Elyamany, A.;Lashin, S.",2011,March,http://dx.doi.org/10.1007/s12072-010-9241-z,0,0,
1758,Wilson disease,"Wilson disease is an autosomal recessive disorder of copper metabolism resulting in cirrhosis and neuropsychological deterioration. The genetic basis for the excessive deposition of copper in the liver and extrahepatic tissues have been identified, caused by mutations in the ATP7B gene. The classical description of cirrhosis, neurological manifestations and Kayser-Fleischer rings is present in a minority of cases. Clinical features are age-dependent: in children, liver disease predominate whereas neurologic manifestations typically present during young adulthood. The spectrum of liver disease ranges from asymptomatic elevation of aminotransferases to acute liver failure. The clinical and liver histological features of Wilson disease can be indistinguishable from autoimmune hepatitis. The diagnosis of Wilson disease relies on a combination of clinical manisfestation and biochemical parameters (low serum caeruloplasmin, high 24-hour urine copper excretion, high hepatic copper concentration). Molecular genetic testing is costly and not widely available. Treatment for Wilson disease include chelating agents such as penicillamine or trientine, zinc and dietary avoidance of high copper-containing food. Patients with fulminant presentation or decompensated cirrhosis require urgent or prompt evaluation for liver transplantation.",Wilson disease;liver;Asian;concentration (parameters);liver cirrhosis;liver disease;excretion;genetic screening;food;patient;decompensated liver cirrhosis;liver transplantation;autosomal recessive disorder;copper metabolism;deterioration;mutation;gene;clinical feature;child;neurologic disease;liver failure;tissue;autoimmune hepatitis;diagnosis;serum;urine;adulthood;copper;chelating agent;penicillamine;trientine;zinc;aminotransferase;ceruloplasmin,"Mohamed, R.",2011,March,http://dx.doi.org/10.1007/s12072-010-9241-z,0,0,
1759,Adjunctive vitamin E treatment in wilson disease and suggestions for future trials,,adjuvant therapy;Alzheimer disease/dt [Drug Therapy];atherosclerosis;cognition;human;letter;monotherapy;nonhuman;oxidative stress;priority journal;vitamin blood level;vitamin supplementation;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha tocopherol/dt [Drug Therapy];copper ion/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];transition element/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Liang, S.;Ji, H. F.",2010,May,http://dx.doi.org/10.1002/hep.23665,0,0,
1760,Wilson's disease with Heterotaxy syndrome: A Case Report,"Wilson's disease (hepatolenticular degeneration) is a rare, treatable, autosomal disorder of copper metabolism leading to liver and brain damage. Its incidence is 1/500,000-1/100,000 live births with more than 250 different mutations [1]. However its association with Heterotaxy syndrome in the form of situs inversus totalis has not been reported till date in Indian literature. We report such a case admitted to our hospital.",Heterotaxy;Situs inversus totalis;Wilson's disease;anasarca;article;autopsy;body posture;case report;child;dextrocardia/di [Diagnosis];dysarthria;dystonia/di [Diagnosis];echography;electrocardiogram;eye examination;female;hepatic encephalopathy/co [Complication];hepatorenal syndrome/co [Complication];heterotaxy syndrome/di [Diagnosis];human;human tissue;hydronephrosis/di [Diagnosis];jaundice/co [Complication];limb tremor;liver biopsy;liver cirrhosis/di [Diagnosis];neurologic examination;pathological laughter;school child;situs inversus/di [Diagnosis];speech disorder;thorax radiography;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Sriram, P.;Arumugaswamy, S.;Mondal, N.;Chaudary, B.;Arun, G. K.",2010,July - December,,0,0,
1761,[The reassessment of the diagnostic value of 24-hour urinary copper excretion in children with Wilson's disease]. [Chinese],"To reassess the diagnostic value of 24 hour urinary copper excretion in children with Wilson disease (WD). From July 2005 to June 2007, inpatients over three years old in a pediatric liver center were assigned into WD and non-WD group. 94 patients, including 26 cases in WD and 68 in non-WD group, were enrolled in this study. The median of 24 h urinary copper excretion was 98.5 microg in WD group and 25.8 microg in the non-WD group (Z = -6.111, P equal to 0.000). The area under receiver operator curve (ROC) was 0.909 (95% CI: 0.839-0.979, P equal to 0.000). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6% and 93.9% respectively using 52.0 ug as a cutoff value, and 50.0%, 97.1%, 84.0%, 86.7% and 83.5% using 100 microg as a cutoff value. The goodness of fitness of 52 microg criteria was significantly higher than 100 microg criteria (kappacoefficient 0.760, 0.541 respectively, P equal to 0.000). Comparing to 100, 52 microg of 24 h urinary copper excretion as a cutoff value significantly improves the sensitivity and accuracy for diagnosing WD in children.",adolescent;age;article;child;female;hepatitis/di [Diagnosis];hepatitis A/di [Diagnosis];human;liver;male;pathology;predictive value;preschool child;receiver operating characteristic;sensitivity and specificity;time;urine;Wilson disease/di [Diagnosis];ceruloplasmin;copper;diagnostic agent;penicillamine,"Lu, Y.;Liu, X. Q.;Wang, X. H.;Wang, J. S.",2010,Jan,,0,0,
1762,A novel COMMD1 mutation Thr174Met associated with elevated urinary copper and signs of enhanced apoptotic cell death in a Wilson Disease patient,,apoptosis;article;ceruloplasmin blood level;child;disease course;dystonia;gene identification;gene mutation;genetic association;genetic screening;genotype phenotype correlation;human;hypersalivation;involuntary movement;language disability;major clinical study;male;mental deterioration;mental disease;nucleotide sequence;priority journal;school child;slurred speech;thr 174 met;treatment response;urine level;Wilson disease;ceruloplasmin;copper;penicillamine;protein commd1/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound],"Gupta, A.;Chattopadhyay, I.;Mukherjee, S.;Sengupta, M.;Das, S. K.;Ray, K.",2010,15 Jun,http://dx.doi.org/10.1186/1744-9081-6-33,0,0,
1763,Neurologic Wilson's disease,"Despite a long history, Wilson's disease, an autosomal recessive disease caused by mutations in the ATP7B gene, remains a commonly misdiagnosed import disease. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. Clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, and choreoathetosis. Among neurodegenerative diseases, it is unusual in that misdiagnosis and delay in treatment are clinically relevant because treatments can prevent and cure Wilson's disease, if they are given appropriately. If left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability and death, while those adequately treated have normal life spans. This review focuses on the neurologic features of Wilson's disease, its diagnosis, and treatment options. © 2009 New York Academy of Sciences.",Ceruloplasmin;Copper;Dysarthria;Dystonia;Movement disorders;Parkinsonism;Tremor;anemia/si [Side Effect];ataxia;autosomal inheritance;brain disease;ceruloplasmin blood level;choreoathetosis;clinical trial;cognitive defect;death;diagnostic error;differential diagnosis;disability;disease course;drug efficacy;drug eruption/si [Side Effect];drug substitution;drug withdrawal;dystonia/dt [Drug Therapy];dystonia/th [Therapy];essential tremor/dt [Drug Therapy];eye disease;gait disorder;human;hyperreflexia;hypersensitivity/si [Side Effect];hypersensitivity reaction/dt [Drug Therapy];kidney disease/si [Side Effect];leukopenia/si [Side Effect];liver disease;liver failure;mental disease;molecular genetics;neurological complication/si [Side Effect];nuclear magnetic resonance imaging;parkinsonism/dt [Drug Therapy];pathogenesis;review;screening;seizure;side effect/si [Side Effect];slit lamp;speech therapy;stereotypy;stomach discomfort/si [Side Effect];systemic lupus erythematosus/si [Side Effect];therapy delay;thrombocytopenia/si [Side Effect];tic;treatment outcome;treatment response;unspecified side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/pc [Prevention];baclofen/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];diazepam/dt [Drug Therapy];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];levodopa/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];primidone/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy],"Lorincz, M. T.",2010,January,http://dx.doi.org/10.1111/j.1749-6632.2009.05109.x,0,0,
1764,A novel mutation in ATP7B gene associated with severe neurological impairment in Wilson's disease. [French],,adolescent;akinesia;ATP7B gene;case report;clinical feature;diagnostic imaging;disease severity;female;gene;gene mutation;gene sequence;human;image analysis;letter;neuroimaging;neurologic disease;sequence analysis;symptom;Wilson disease;penicillamine,"Elleuch, N.;Feki, I.;Turki, E.;Miladi, M. I.;Boukhris, A.;Damak, M.;Mhiri, C.;Chappuis, E.;Woimant, F.",2010,May,http://dx.doi.org/10.1016/j.neurol.2009.10.008,0,0,
1765,Nephrolithiasis related to inborn metabolic diseases,"Nephrolithiasis associated with inborn metabolic diseases is a very rare condition with some common characteristics: early onset of symptoms, family history, associated tubular impairment, bilateral, multiple and recurrent stones, and association with nephrocalcinosis. The prognosis of such diseases may lead to life threatening conditions, not only because of unabated kidney damage but also because of progressive extra-renal involvement, either in a systemic form (e.g. primary hyperoxaluria type 1, requiring combined liver and kidney transplantation), or in a neurological form (Lesch-Nyhan syndrome leading to automutilation and disability, phosphoribosyl pyrophosphate synthetase superactivity, which is associated with mental retardation). Patients with other inborn metabolic diseases present only with recurrent stone formation, such as cystinuria, adenine phosphoribosyl-transferase deficiency, xanthine deficiency. Finally, nephrolithiasis may be secondarily part of some other metabolic diseases, such as glycogen storage disease type 1 or inborn errors of metabolism leading to Fanconi syndrome (nephropathic cystinosis, tyrosinaemia type 1, fructose intolerance, Wilson disease, respiratory chain disorders, etc.). The diagnosis is based on highly specific investigations, including crystal identification, biochemical analyses and DNA study. The treatment of nephrolithiasis requires hydration as well as specific measures. Compliance is a major issue regarding the progression of renal damage, but the overall outcome mainly depends on extra-renal involvement in relation to the metabolic defect. © IPNA 2009.",Cystinuria;Fanconi syndrome;Glycogen storage disease type 1;Nephrocalcinosis;Nephrolithiasis;Primary hyperoxaluria;Purine metabolism;Pyrimidine metabolism;Uric acid;Xanthine;automutilation;blue diaper syndrome/et [Etiology];carbohydrate intolerance/et [Etiology];crystalluria;cystinuria/dt [Drug Therapy];cystinuria/th [Therapy];diet restriction;differential diagnosis;disease association;disease course;disorders of purine and pyrimidine metabolism/et [Etiology];DNA determination;enzyme activity;enzyme deficiency/et [Etiology];extracorporeal lithotripsy;Fanconi renotubular syndrome/et [Etiology];fluid intake;glomerulus filtration rate;glucose transport;glycogen storage disease type 1/et [Etiology];hemodialysis;human;hyperuricemia;hyperuricosuria;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/et [Etiology];incidence;kidney calcification;kidney cystine stone/dt [Drug Therapy];kidney failure/co [Complication];kidney failure/th [Therapy];kidney injury;kidney transplantation;Lesch Nyhan syndrome/di [Diagnosis];Lesch Nyhan syndrome/dt [Drug Therapy];Lesch Nyhan syndrome/et [Etiology];liver transplantation;mental deficiency;nephrolithiasis/dt [Drug Therapy];nephrolithiasis/et [Etiology];nephrolithiasis/su [Surgery];nephrolithiasis/th [Therapy];oxalosis 1/di [Diagnosis];oxalosis 1/dt [Drug Therapy];oxalosis 1/ep [Epidemiology];oxalosis 1/et [Etiology];oxalosis 1/th [Therapy];phenotype;primary hyperoxaluria type 2/di [Diagnosis];primary hyperoxaluria type 2/et [Etiology];priority journal;prognosis;review;sodium intake;stone formation;3 methylglutaconic acid;5 oxoprolinase/ec [Endogenous Compound];acetylcysteine/dt [Drug Therapy];adenine phosphoribosyltransferase/ec [Endogenous Compound];allopurinol/dt [Drug Therapy];bicarbonate/dt [Drug Therapy];citrate potassium/dt [Drug Therapy];citrate sodium/dt [Drug Therapy];glyceric acid/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phosphate/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];ribosephosphate pyrophosphokinase/ec [Endogenous Compound];tiopronin/dt [Drug Therapy];whewellite;xanthine oxidase/ec [Endogenous Compound],"Cochat, P.;Pichault, V.;Bacchetta, J.;Dubourg, L.;Sabot, J. F.;Saban, C.;Daudon, M.;Liutkus, A.",2010,March,http://dx.doi.org/10.1007/s00467-008-1085-6,0,0,
1766,Review article: Te current management of acute liver failure,"Aliment Pharmacol Ther 31, 345-358 SummaryBackground Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. Aim To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. Methods Literature review using Ovid, PubMed and recent conference abstracts. Results Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and 'buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. Conclusion Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT. © 2010 Blackwell Publishing Ltd.",abdominal pain;adult respiratory distress syndrome;anorexia;bioartificial liver;blood clotting disorder;brain edema/dt [Drug Therapy];chelation therapy;clinical feature;clinical trial;drug overdose;fatigue;fatty liver;fever;HELLP syndrome;hemodynamics;hepatic encephalopathy;hepatitis B/dt [Drug Therapy];human;intracranial pressure monitoring;jaundice;kidney failure;liver failure/co [Complication];liver failure/dt [Drug Therapy];liver failure/ep [Epidemiology];liver failure/et [Etiology];liver failure/su [Surgery];liver failure/th [Therapy];liver transplantation;morbidity;mushroom poisoning/dt [Drug Therapy];nonhuman;plasmapheresis;priority journal;prognosis;review;seizure/si [Side Effect];sepsis;systemic inflammatory response syndrome;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];acetylcysteine/ct [Clinical Trial];acetylcysteine/dt [Drug Therapy];acetylcysteine/pd [Pharmacology];aciclovir/dt [Drug Therapy];aciclovir/iv [Intravenous Drug Administration];beta interferon;cocaine;corticosteroid derivative/dt [Drug Therapy];disulfiram;foscarnet/dt [Drug Therapy];glucagon/dt [Drug Therapy];halothane;Human immunodeficiency virus antibody;indometacin/dt [Drug Therapy];insulin/dt [Drug Therapy];lamivudine/ct [Clinical Trial];lamivudine/dt [Drug Therapy];macrolide;mannitol/dt [Drug Therapy];nonsteroid antiinflammatory agent;ornithine aspartate/ae [Adverse Drug Reaction];ornithine aspartate/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy];penicillin G/dt [Drug Therapy];propofol/dt [Drug Therapy];prostaglandin E2/dt [Drug Therapy];silibinin/dt [Drug Therapy];sodium chloride/dt [Drug Therapy];sulfonamide;tetracycline derivative;thalidomide;thiopental/dt [Drug Therapy];tuberculostatic agent;valproic acid,"Craig, D. G. N.;Lee, A.;Hayes, P. C.;Simpson, K. J.",2010,February,http://dx.doi.org/10.1111/j.1365-2036.2009.04175.x,0,0,
1767,Triethylene tetramine dihydrochloride (trientine) in children with Wilson disease: experience at King's College Hospital and review of the literature,"Our aim was to review our experience of trientine as chelation therapy in children with Wilson disease (WD) and compare to that reported in the literature. We made a retrospective review of the medical notes of 16 of 96 (17%) children diagnosed with WD between 1981 and 2006. Children were 6.6 to 15 years old. Only three received trientine as initial therapy [parental choice (two), allergic reactions to penicillamine (one) during the penicillamine challenge], 13 of 16 were converted from penicillamine to trientine because of reactions to penicillamine: haematuria in four, bone marrow suppression in three, neutropenia in three. Trientine was discontinued in three due to allergic rash, low copper excretion and one with compliance problems requiring transplantation. Seventy-five per cent of children presented with chronic liver disease. Kayser-Fleischer rings were noticed in eight of 16, Wilson Ferenci score range was between 4 and 10 (nl < 4). Laboratory indices remained relatively stable. In line with previous reports, trientine was used mainly as secondary treatment when there were severe side effects with penicillamine. Whilst the current evidence is low quality, it appears that trientine is as efficacious as penicillamine and small population studies show a lower side effect profile.","adolescent;brain;chelation therapy;child;female;follow up;human;liver;male;methodology;nuclear magnetic resonance imaging;pathology;pathophysiology;residential care;retrospective study;review;Wilson disease/ep [Epidemiology];Wilson disease/th [Therapy];1,4 diazabicyclo[2.2.2]octane;chelating agent/dt [Drug Therapy];piperazine derivative/dt [Drug Therapy]","Taylor, R. M.;Chen, Y.;Dhawan, A.",2009,Sep,,0,1,
1768,Agents complexing copper as a therapeutic strategy for the treatment of Alzheimer's disease,"The notion that a copper dysfunction is implicated in Alzheimer's disease (AD) is based on a number of observations from in vitro and clinical studies, as well as animal models. However, there is still significant controversy over whether it is an excess or a deficiency of copper to be involved in the pathogenesis of AD. Numerous studies support the hypothesis that an excess of copper contributes to AD, but experimental evidence in transgenic mouse models seems to suggest the contrary, and at least one clinical study shows that cognitive decline correlates positively with low copper levels. We have recently reported on a deregulation of the ceruloplasmin-copper relationship, specific to AD patients, consisting of an elevation of the copper pool not bound to ceruloplasmin, i.e. 'free' copper. This phenomenon could provide an explanation of the contrasting results obtained in clinical studies. Several clinical trials have been attempted in search of an anti-metal effect counteracting AD progression. Some of them have delivered encouraging results indicating that ""metal protein attenuating compounds"" can indeed alter positively the progression of the disease. This review summarizes these clinical studies and provides an overview of those in progress and in preparation. ©2009 Bentham Science Publishers Ltd.",'Free' copper;Alzheimer disease;Ceruloplasmin;Copper;Metal protein attenuating compounds;Therapy;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];biliary excretion;blood brain barrier;cerebrospinal fluid level;clinical trial;cognitive defect;copper blood level;copper deficiency;copper metabolism;disease model;dose response;drug absorption;drug effect;drug efficacy;drug fatality/si [Side Effect];drug mechanism;drug penetration;drug withdrawal;gene expression regulation;genetic risk;heart arrest/si [Side Effect];human;intestine absorption;liver cell;metal binding;molecular interaction;nerve cell lesion;neurofibrillary tangle;neuropathology;neuroprotection;nonhuman;oxidation reduction reaction;oxidative stress;priority journal;protein aggregation;protein cleavage;protein expression;protein function;regulatory mechanism;review;senile plaque;treatment outcome;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/si [Side Effect];amyloid precursor protein/ec [Endogenous Compound];apolipoprotein E4/ec [Endogenous Compound];beta secretase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chaperone/it [Drug Interaction];chaperone/ec [Endogenous Compound];cholinesterase inhibitor/dt [Drug Therapy];clioquinol/ct [Clinical Trial];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pk [Pharmacokinetics];clioquinol/pd [Pharmacology];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper chaperone for superoxide dismutase protein/it [Drug Interaction];copper chaperone for superoxide dismutase protein/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];cytochrome c oxidase assembly homologue proetin/it [Drug Interaction];cytochrome c oxidase assembly homologue proetin/ec [Endogenous Compound];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/ct [Clinical Trial];deferoxamine/dt [Drug Therapy];gamma secretase/ec [Endogenous Compound];homocysteine/ec [Endogenous Compound];human atox 1 homologue protein/it [Drug Interaction];human atox 1 homologue protein/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];metal bis(thiosemicarbazonato)/dv [Drug Development];metal chelate/dv [Drug Development];metallothionein III/ec [Endogenous Compound];pbt 2/ct [Clinical Trial];pbt 2/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];peroxide/ec [Endogenous Compound];placebo;tau protein/ec [Endogenous Compound];tetrathiomolybdate ammonium/ct [Clinical Trial];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/pk [Pharmacokinetics];unclassified drug;Wilson disease protein/ec [Endogenous Compound],"Squitti, R.;Salustri, C.",2009,December,http://dx.doi.org/10.2174/156720509790147133,0,0,
1769,Matrix metalloproteinases and their inhibitors as markers of inflammation and fibrosis in chronic liver disease (Review),"Chronic liver disease (CLD) is a cause of morbidity and mortality worldwide, due to haemodynamic and metabolic complications of liver cirrhosis. During CLD the extracellular matrix undergoes a process of remodelling, leading to new collagen formation and deposition. Tissue remodelling is regulated by fine molecular mechanisms, involving proteases, inhibitors and growth factors. The major role in matrix degradation is played by matrix metalloproteinases (MMPs), a class of zinc and calcium-dependent enzymes, and their tissue inhibitors (TIMPs). Along with the progress in diagnostic techniques, leading to more precise and less invasive methods, the concept of monitoring has gained importance for the clinical management of CLD. At the present state of our knowledge, liver biopsy still represents an essential procedure for staging liver disease. However, despite its importance, liver biopsy presents some limitations: the risk of a disease underestimation is the most significant one, as hepatic lesions are often irregularly located within the liver. Parallel to the limitations of liver biopsy, clinical needs for an early identification of progressive fibrosis require additional non-invasive techniques to be developed. In this review we discuss the major problems concerning this important clinical necessity. Moreover, we focus on the role of MMPs and TIMPs in the pathogenesis of CLD, as well as their possible use as non-invasive serum markers for inflammation and fibrosis in this pathology.",Chronic liver disease;Fibrosis;Inflammation;Matrix metalloproteinases;alanine aminotransferase blood level;alcohol abuse;aspartate aminotransferase blood level;disease course;disease marker;disease severity;enzyme activity;enzyme inhibition;enzyme substrate;extracellular matrix;hemochromatosis;hepatitis B;hepatitis C;histopathology;human;liver biopsy;liver cirrhosis;liver fibrosis;nonalcoholic fatty liver;priority journal;prognosis;protein blood level;protein domain;protein expression;review;structure analysis;Wilson disease;alpha 2 macroglobulin/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];collagenase 3/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];gelatinase A/ec [Endogenous Compound];gelatinase B/ec [Endogenous Compound];hyaluronic acid/ec [Endogenous Compound];interstitial collagenase/ec [Endogenous Compound];macrophage elastase/ec [Endogenous Compound];matrix metalloproteinase/ec [Endogenous Compound];matrix metalloproteinase 14/ec [Endogenous Compound];matrix metalloproteinase 15/ec [Endogenous Compound];matrix metalloproteinase 16/ec [Endogenous Compound];matrix metalloproteinase 17/ec [Endogenous Compound];matrix metalloproteinase 18/ec [Endogenous Compound];matrix metalloproteinase 19/ec [Endogenous Compound];matrix metalloproteinase 20/ec [Endogenous Compound];matrix metalloproteinase 21/ec [Endogenous Compound];matrix metalloproteinase 22/ec [Endogenous Compound];matrix metalloproteinase 23/ec [Endogenous Compound];matrix metalloproteinase 24/ec [Endogenous Compound];matrix metalloproteinase 25/ec [Endogenous Compound];matrix metalloproteinase 27/ec [Endogenous Compound];neutrophil collagenase/ec [Endogenous Compound];stromelysin/ec [Endogenous Compound];stromelysin 2/ec [Endogenous Compound];stromelysin 3/ec [Endogenous Compound];tissue inhibitor of metalloproteinase/ec [Endogenous Compound];unclassified drug,"Consolo, M.;Amoroso, A.;Spandidos, D. A.;Mazzarino, M. C.",2009,,http://dx.doi.org/10.3892/ijmm_00000217,0,0,
1770,Tracing copper-thiomolybdate complexes in a prospective treatment for Wilson's disease,"Wilson's disease is a human genetic disorder which results in copper accumulation in liver and brain. Treatments such as copper chelation therapy or dietary supplementation with zinc can ameliorate the effects of the disease, but if left untreated, it results in hepatitis, neurological complications, and death. Tetrathiomolybdate (TTM) is a promising new treatment for Wilson's disease which has been demonstrated both in an animal model and in clinical trials. X-ray absorption spectroscopy suggests that TTM acts as a novel copper chelator, forming a complex with accumulated copper in liver. We have used X-ray absorption spectroscopy and X-ray fluorescence imaging to trace the molecular form and distribution of the complex in liver and kidney of an animal model of human Wilson's disease. Our work allows new insights into metabolism of the metal complex in the diseased state. © 2009 American Chemical Society.",absorption spectroscopy;animal experiment;animal model;animal tissue;article;controlled study;copper metabolism;kidney parenchyma;liver;nonhuman;priority journal;rat;roentgen spectroscopy;single drug dose;Wilson disease/dt [Drug Therapy];X ray fluorescence;copper;molybdenum;tetrathiomolybdic acid/dt [Drug Therapy],"Zhang, L.;Lichtmannegger, J.;Summer, K. H.;Webb, S.;Pickering, I. J.;George, G. N.",2009,10 Feb,http://dx.doi.org/10.1021/bi801926e,0,0,
1771,Hepatobiliary and pancreatic: Hypersensitivity pneumonitis induced by penicillamine,,adult;allergic pneumonitis/si [Side Effect];article;case report;drug substitution;drug withdrawal;dyspnea;female;human;human cell;liver cirrhosis;liver function test;lung lavage;priority journal;thorax radiography;treatment response;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Seo, J. Y.;Kim, S. Y.;Choi, W. C.",2009,April,http://dx.doi.org/10.1111/j.1440-1746.2009.05819.x,0,0,
1772,Wilson's disease - A rare psychiatric presentation,"The development of extrapyramidal syndrome characterised by rigidity, bradykinesia, dysphagia and dysarthria in a male individual with four distinct episodes of (mania like) behavioural disturbances with fairly good remission in a time frame of five years, in a male individual ,was suspected to develop the neurological manifestations of Wilson's disease and was investigated. In the absence of Kayser-Fleischer ring by slit-lamp examination and with normal copper and ceruloplasmin serum levels, the diagnosis was possible because of the positive findings of the magnetic resonance imaging (MRI) studies and increased 24 hours urinary copper levels with the penicillamine challenge test. The findings and its implications are highlighted and discussed.",Extrapyramidal syndrome;Mania-like;Penicillamine challenge test;Wilson's disease;adult;article;bedtime dosage;bipolar disorder;bradykinesia;case report;ceruloplasmin blood level;computer assisted tomography;copper blood level;dysarthria;dysphagia;hospitalization;human;male;mania;neurologic disease;nuclear magnetic resonance imaging;provocation test;psychomotor activity;remission;rigidity;slit lamp;supplementation;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chlorpromazine/dt [Drug Therapy];copper/ec [Endogenous Compound];haloperidol/dt [Drug Therapy];haloperidol/im [Intramuscular Drug Administration];penicillamine;sodium/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];thyroxine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];valproic acid/dt [Drug Therapy],"Aravind, V. K.;Krishnaram, V. D.;Neethiarau, V.;Srinivasan, K. G.",2009,July,,0,0,
1773,New developments in the regulation of intestinal copper absorptionn,"The transition metal copper is an essential trace element involved in many enzymatic processes that require redox-chemistry. The redox-activity of copper is potentially harmful. Severe imbalance of copper homeostasis can occur with some hereditary disorders of copper metabolism. Copper is acquired from the diet by intestinal absorption and is subsequently distributed throughout the body. The regulation of intestinal copper absorption to maintain whole-body copper homeostasis is currently poorly understood. This review evaluates novel findings regarding the molecular mechanism of intestinal copper uptake. The role of recently identified transporters in enterocyte copper uptake and excretion into the portal circulation is described, and the regulation of dietary copper uptake during physiological and pathophysiological conditions is discussed. © 2009 International Life Sciences Institute.",atp7a;Copper;hctr1;Homeostasis;Intestine;copper metabolism;dietary intake;enzyme activity;excretion;human;intestine absorption;intestine cell;Menkes syndrome/dt [Drug Therapy];nonhuman;oxidation reduction reaction;portal vein blood flow;protein function;regulatory mechanism;review;Wilson disease/dt [Drug Therapy];carrier protein/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/sc [Subcutaneous Drug Administration];histidine/dt [Drug Therapy];histidine/sc [Subcutaneous Drug Administration];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Van Den Berghe, P. V. E.;Klomp, L. W. J.",2009,November,http://dx.doi.org/10.1111/j.1753-4887.2009.00250.x,0,0,
1774,Wilson's disease. [Czech],"Wilson's disease is an inherited disorder leading to accumulation of copper in tissues, mainly in the liver and brain. Genetic defect is in the gene coding ATPase type P (ATP7B). The inheritance is autosomal recessive. Up to now, more then 500 mutations causing Wilson's disease were described. The most frequent mutation in Central Europe is mutation H1069Q. The manifestation of Wilson's disease is usually hepatic or neurologic. Hepatic form is manifested by acute or chronic hepatitis, steatosis or cirrhosis. Neurologic involvement is manifested usually after 20 year of age by motor disturbances (tremor, disturbed speech, problems with writing), which could progress into severe extrapyramidal syndrome with tremor, rigidity, dysartria, dysfagia and muscle contracture. Diagnosis is based on clinical and laboratory examinations (neurologic symptoms, liver disease, low serum ceruloplasmin levels, elevated free copper concentration in serum, high urine copper excretion, and presence of Kayser-Fleischer rings). Confirmation of diagnosis is done by hepatic copper concentration in liver biopsy or by genetic examination. Untreated disease leads to the death of a patient. Treatment is based on chelating agents decreasing the copper content by excretion into urine (D-penicillamine, trientine) or on agents preventing absorption of copper from food (zinc, ammonium-tetrahiomolybdene). Patients with asymptomatic Wilson's disease have to be treated as well. In Czech Republic either penicillamine or zinc are used. Liver transplantation is indicated in patients with fulminant liver failure or decompensated cirrhosis. Screening in families of affected patients (all siblings) is obvious.",Copper metabolism;Extrapyramidal syndrome;Liver cirrhosis;Penicillamine;Wilson's disease;Zinc;article;genetics;human;prognosis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy],"Bruha, R.;Marecek, Z.;Martasek, P.;Nevsimalova, S.;Petrtyl, J.;Urbanek, P.;Kalistova, H.;Pospisilova, L.",2009,,,0,0,
1775,Orphan drugs. [French],,"acute granulocytic leukemia/dt [Drug Therapy];article;chronic myeloid leukemia/dt [Drug Therapy];drug indication;Fabry disease/dt [Drug Therapy];glycogen storage disease type 2/dt [Drug Therapy];hemochromatosis/dt [Drug Therapy];homocystinuria/dt [Drug Therapy];human;Hunter syndrome/dt [Drug Therapy];Hurler syndrome/dt [Drug Therapy];hyperammonemia/dt [Drug Therapy];leukemia/dt [Drug Therapy];Morquio syndrome/dt [Drug Therapy];multiple myeloma/dt [Drug Therapy];myoclonus epilepsy/dt [Drug Therapy];neoplasm/dt [Drug Therapy];patent ductus arteriosus/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase beta/dt [Drug Therapy];ambrisentan/dt [Drug Therapy];betaine/dt [Drug Therapy];bosentan/dt [Drug Therapy];carbidopa plus levodopa;carglumic acid/dt [Drug Therapy];dasatinib/dt [Drug Therapy];deferasirox/dt [Drug Therapy];erlotinib;galsulfase/dt [Drug Therapy];histamine/dt [Drug Therapy];ibuprofen/dt [Drug Therapy];iduronate 2 sulfatase/dt [Drug Therapy];iloprost/dt [Drug Therapy];imatinib/dt [Drug Therapy];laronidase/dt [Drug Therapy];lenalidomide/dt [Drug Therapy];nilotinib/dt [Drug Therapy];orphan drug;recombinant glucan 1,4 alpha glucosidase/dt [Drug Therapy];recombinant somatomedin C;sildenafil/dt [Drug Therapy];sitaxsentan/dt [Drug Therapy];sorafenib/dt [Drug Therapy];stiripentol/dt [Drug Therapy];sunitinib;thalidomide/dt [Drug Therapy];unclassified drug;unindexed drug;wilzin;zinc acetate/dt [Drug Therapy]","Dooms, P. M.",2009,March,,0,0,
1776,The conquest of Wilsons disease,,acute kidney tubule necrosis/si [Side Effect];ceruloplasmin blood level;drug blood level;drug effect;drug mechanism;drug substitution;drug withdrawal;epigastric pain/si [Side Effect];fever/si [Side Effect];hemolytic anemia/si [Side Effect];human;immune complex nephritis/si [Side Effect];kidney disease/si [Side Effect];liver biopsy;liver transplantation;nonhuman;priority journal;review;structure activity relation;systemic lupus erythematosus/si [Side Effect];treatment outcome;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];alpha tocopherol/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/an [Drug Analysis];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];dimercaprol/pk [Pharmacokinetics];dimercaprol/pd [Pharmacology];edetic acid/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/pd [Pharmacology];pyridoxine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology];thiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/dt [Drug Therapy];zinc derivative/pe [Pharmacoeconomics];zinc derivative/pd [Pharmacology],"Walshe, J. M.",2009,August,http://dx.doi.org/10.1093/brain/awp149,0,0,
1777,Clinical character and therapeutic effect of late-onset Wilson disease. [Chinese],"Objective To investigate the clinical character and therapeutic effect of late-onset Wilson disease , and to provide some evidence for its diagnosis and treatment. Methods Clinical character, changes of copper metabolism, and therapeutic effect of 8 patients with late-onset Wilson disease were analyzed. Ceruloplasmin level was measured by nephelometry , and the copper contents in the serum, urine, and liver were measured by flame atomic absorption spectroscopy. The initial treatment was sodium dimercaptosulphonate, followed by D-penicillamine and/or zinc. Results Patients with late - onset Wilson disease accounted for 7.0 % of all patients, Who presented liver disease symptoms such as loss of appetite or nausea at the early stage and were misdiagnosed easily. Their blood routine and aminotransferase levels were normal in most patients with late - onset Wilson disease, and all patients had Kayser-Fleisher rings. There was significant difference between the liver function and copper metabolite test. The average urinary copper content was 4 072 mug/24 h on the first day after administrating sodium dimercaptosulphonate, which was 18.1 times as much as that before the treatment, and 2.5 times as much as that of D-penicillamine. No obvious adverse reactions were observed. The prognosis was usually good. Conclusion Enough attention should be paid to late-onset Wilson disease which is not rare and easy to be misdiagnosed. Good response can be expected in patients treated with sodium dimercaptosulphonate in the initial stage.",Ceruloplasmin;Kayser-fleisher rings;Sodium dimercaptosulphonate;Urinary copper;Wilson disease;adolescent;adult;article;child;female;human;male;metabolism;middle aged;preschool child;prognosis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Zhang, Y.;Yang, X.;Tang, X.;Luo, H.;Lei, J.",2009,January,,0,0,
1778,Liver disease in pregnancy,"Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/ eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy. © 2009 The WJG Press and Baishideng. All rights reserved.",Cesarean section;Cholestasis;Fetal outcome;Liver disease;Maternal outcome;Pregnancy;Viral hepatitis;acute fatty liver of pregnancy/di [Diagnosis];acute fatty liver of pregnancy/et [Etiology];autoimmune hepatitis/dt [Drug Therapy];breast feeding;cholecystectomy;chronic liver disease;clinical feature;clinical trial;congenital malformation;eclampsia/dt [Drug Therapy];editorial;embryotoxicity;endoscopic retrograde cholangiopancreatography;fetus mortality;gallstone/et [Etiology];gallstone/su [Surgery];gallstone/th [Therapy];HELLP syndrome/dt [Drug Therapy];HELLP syndrome/et [Etiology];HELLP syndrome/th [Therapy];hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];hepatitis C/dt [Drug Therapy];human;hyperemesis gravidarum/dt [Drug Therapy];hyperemesis gravidarum/th [Therapy];infection prevention;intrahepatic cholestasis/di [Diagnosis];intrahepatic cholestasis/dt [Drug Therapy];intrahepatic cholestasis/et [Etiology];labor induction;liver cirrhosis;liver disease/di [Diagnosis];liver disease/et [Etiology];liver disease/th [Therapy];low birth weight;low drug dose;malabsorption/dt [Drug Therapy];maternal mortality;nonhuman;pathophysiology;perinatal mortality;preeclampsia/dt [Drug Therapy];prenatal drug exposure;primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/dt [Drug Therapy];pruritus/dt [Drug Therapy];respiration depression/si [Side Effect];small for date infant;teratogenicity;vertical transmission;Wilson disease/dt [Drug Therapy];acetylsalicylic acid/dt [Drug Therapy];acetylsalicylic acid/to [Drug Toxicity];anticoagulant agent/dt [Drug Therapy];antihistaminic agent/dt [Drug Therapy];azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];azathioprine/to [Drug Toxicity];beta adrenergic receptor blocking agent/dt [Drug Therapy];beta adrenergic receptor blocking agent/to [Drug Toxicity];calcium channel blocking agent/dt [Drug Therapy];calcium channel blocking agent/to [Drug Toxicity];colestyramine/ct [Clinical Trial];colestyramine/cm [Drug Comparison];colestyramine/dt [Drug Therapy];dexamethasone/dt [Drug Therapy];dipeptidyl carboxypeptidase inhibitor/dt [Drug Therapy];dipeptidyl carboxypeptidase inhibitor/to [Drug Toxicity];enoxaparin/to [Drug Toxicity];hepatitis B antibody/dt [Drug Therapy];hepatitis B vaccine/dt [Drug Therapy];lamivudine/dt [Drug Therapy];magnesium sulfate/dt [Drug Therapy];metoclopramide/dt [Drug Therapy];octreotide;ondansetron/dt [Drug Therapy];peginterferon/cb [Drug Combination];peginterferon/dt [Drug Therapy];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];prochlorperazine/dt [Drug Therapy];prochlorperazine/to [Drug Toxicity];promethazine/ae [Adverse Drug Reaction];promethazine/dt [Drug Therapy];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];ribavirin/to [Drug Toxicity];s adenosylmethionine/ct [Clinical Trial];s adenosylmethionine/cm [Drug Comparison];s adenosylmethionine/dt [Drug Therapy];steroid/cb [Drug Combination];steroid/dt [Drug Therapy];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];unindexed drug;ursodeoxycholic acid/ct [Clinical Trial];ursodeoxycholic acid/cm [Drug Comparison];ursodeoxycholic acid/dt [Drug Therapy];vasopressin/to [Drug Toxicity];vitamin K group/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity],"Lee, N. M.;Brady, C. W.",2009,28 Feb,http://dx.doi.org/10.3748/wjg.15.897,0,0,
1779,Chelation in metal intoxication,"Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications. © 2010 by the authors.",Antioxidant;Chelating agents;Combination therapy;Heavy metals;Oxidative stress;Succimer monoesters;absence of side effects/si [Side Effect];ageusia/si [Side Effect];agranulocytosis/si [Side Effect];allergic pneumonitis/si [Side Effect];aluminum overload/dt [Drug Therapy];anorexia/si [Side Effect];aplastic anemia/si [Side Effect];arsenic poisoning/dt [Drug Therapy];arthropathy/si [Side Effect];bacterial infection/dt [Drug Therapy];blood disease/dt [Drug Therapy];cadmium poisoning/dt [Drug Therapy];carcinogenicity;chelation therapy;chest tightness/si [Side Effect];chill/si [Side Effect];clinical effectiveness;clinical trial;complex formation;conjunctivitis/si [Side Effect];dermatomyositis/si [Side Effect];diarrhea/si [Side Effect];drug absorption;drug antagonism;drug binding;drug blood level;drug dose comparison;drug dose reduction;drug elimination;drug fever/si [Side Effect];drug half life;drug hypersensitivity/dt [Drug Therapy];drug hypersensitivity/si [Side Effect];drug induced headache/si [Side Effect];drug mechanism;drug megadose;drug structure;drug withdrawal;dry skin/si [Side Effect];environmental exposure;eye toxicity/si [Side Effect];food;food drug interaction;gastrointestinal symptom/si [Side Effect];genotoxicity;hair loss/si [Side Effect];heavy metal poisoning/dt [Drug Therapy];hemolysis/si [Side Effect];human;hydrophilicity;hypertension/si [Side Effect];injection site infection/si [Side Effect];injection site pain/si [Side Effect];intoxication/dt [Drug Therapy];iron overload/dt [Drug Therapy];lacrimation;ld 50;lead poisoning/dt [Drug Therapy];leukopenia/si [Side Effect];liver injury/si [Side Effect];low drug dose;lung toxicity/dt [Drug Therapy];lupus erythematosus/si [Side Effect];membranous glomerulonephritis/si [Side Effect];mercurialism/dt [Drug Therapy];muscle cramp/si [Side Effect];mycosis/dt [Drug Therapy];nausea/si [Side Effect];nephrotoxicity/dt [Drug Therapy];neurotoxicity/dt [Drug Therapy];neutropenia/si [Side Effect];nonhuman;ototoxicity/dt [Drug Therapy];paresthesia/si [Side Effect];pemphigus/si [Side Effect];polymyositis/si [Side Effect];proteinuria/si [Side Effect];recommended drug dose;review;risk reduction;side effect/si [Side Effect];single drug dose;skin manifestation/dt [Drug Therapy];skin manifestation/si [Side Effect];structure activity relation;tachycardia/si [Side Effect];taste;teratogenicity;thalassemia major/dt [Drug Therapy];thrombocytopenia/si [Side Effect];tremor/si [Side Effect];ulcerogenesis;urinary excretion;vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];zinc deficiency/si [Side Effect];aluminum/to [Drug Toxicity];antimalarial agent/cb [Drug Combination];antimalarial agent/it [Drug Interaction];antioxidant/cb [Drug Combination];antioxidant/cm [Drug Comparison];antioxidant/dt [Drug Therapy];antioxidant/pd [Pharmacology];arsenic/to [Drug Toxicity];cadmium/to [Drug Toxicity];calcium trisodium pentetic acid/ae [Adverse Drug Reaction];calcium trisodium pentetic acid/an [Drug Analysis];calcium trisodium pentetic acid/cb [Drug Combination];calcium trisodium pentetic acid/cm [Drug Comparison];calcium trisodium pentetic acid/do [Drug Dose];calcium trisodium pentetic acid/dt [Drug Therapy];calcium trisodium pentetic acid/to [Drug Toxicity];calcium trisodium pentetic acid/ih [Inhalational Drug Administration];calcium trisodium pentetic acid/im [Intramuscular Drug Administration];calcium trisodium pentetic acid/iv [Intravenous Drug Administration];calcium trisodium pentetic acid/pa [Parenteral Drug Administration];calcium trisodium pentetic acid/pk [Pharmacokinetics];calcium trisodium pentetic acid/pd [Pharmacology];carbodithioic acid derivative/cm [Drug Comparison];carbodithioic acid derivative/dt [Drug Therapy];carbodithioic acid derivative/pd [Pharmacology];chelating agent/an [Drug Analysis];chelating agent/cb [Drug Combination];chelating agent/cm [Drug Comparison];chelating agent/dt [Drug Therapy];chelating agent/pk [Pharmacokinetics];chelating agent/pd [Pharmacology];copper/to [Drug Toxicity];cytotoxic agent/cb [Drug Combination];cytotoxic agent/it [Drug Interaction];deferiprone/ae [Adverse Drug Reaction];deferiprone/ct [Clinical Trial];deferiprone/an [Drug Analysis];deferiprone/cb [Drug Combination];deferiprone/cm [Drug Comparison];deferiprone/do [Drug Dose];deferiprone/it [Drug Interaction];deferiprone/dt [Drug Therapy];deferiprone/po [Oral Drug Administration];deferiprone/pk [Pharmacokinetics];deferiprone/pd [Pharmacology];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/an [Drug Analysis];deferoxamine/cb [Drug Combination];deferoxamine/cm [Drug Comparison];deferoxamine/dt [Drug Therapy];deferoxamine/im [Intramuscular Drug Administration];deferoxamine/iv [Intravenous Drug Administration];deferoxamine/pk [Pharmacokinetics];deferoxamine/pd [Pharmacology];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/an [Drug Analysis];dimercaprol/do [Drug Dose];dimercaprol/dt [Drug Therapy];dimercaprol/to [Drug Toxicity];dimercaprol/im [Intramuscular Drug Administration];dimercaprol/pk [Pharmacokinetics];dimercaprol/pd [Pharmacology];gold/cb [Drug Combination];gold/it [Drug Interaction];heavy metal/to [Drug Toxicity];iron/to [Drug Toxicity];lead/to [Drug Toxicity];mercury/to [Drug Toxicity];metal ion/to [Drug Toxicity];monocyclohexylsuccimer/an [Drug Analysis];monocyclohexylsuccimer/dv [Drug Development];monocyclohexylsuccimer/po [Oral Drug Administration];monocyclohexylsuccimer/pd [Pharmacology];monoisoamylsuccimer/ad [Drug Administration];monoisoamylsuccimer/an [Drug Analysis];monoisoamylsuccimer/cb [Drug Combination];monoisoamylsuccimer/dv [Drug Development];monoisoamylsuccimer/do [Drug Dose];monoisoamylsuccimer/dt [Drug Therapy];monoisoamylsuccimer/to [Drug Toxicity];monoisoamylsuccimer/ip [Intraperitoneal Drug Administration];monoisoamylsuccimer/po [Oral Drug Administration];monoisoamylsuccimer/pk [Pharmacokinetics];monoisoamylsuccimer/pd [Pharmacology];monomethylsuccimer/an [Drug Analysis];monomethylsuccimer/dv [Drug Development];monomethylsuccimer/po [Oral Drug Administration];monomethylsuccimer/pd [Pharmacology];nitrilotriacetic acid/an [Drug Analysis];nitrilotriacetic acid/do [Drug Dose];nitrilotriacetic acid/dt [Drug Therapy];nitrilotriacetic acid/to [Drug Toxicity];nitrilotriacetic acid/pk [Pharmacokinetics];nitrilotriacetic acid/pd [Pharmacology];penicillamine/ae [Adverse Drug Reaction];penicillamine/an [Drug Analysis];penicillamine/cb [Drug Combination];penicillamine/cr [Drug Concentration];penicillamine/do [Drug Dose];penicillamine/it [Drug Interaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/iv [Intravenous Drug Administration];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];succimer/ae [Adverse Drug Reaction];succimer/ct [Clinical Trial];succimer/an [Drug Analysis];succimer/cb [Drug Combination];succimer/cm [Drug Comparison];succimer/dt [Drug Therapy];succimer/to [Drug Toxicity];succimer/im [Intramuscular Drug Administration];succimer/ip [Intraperitoneal Drug Administration];succimer/iv [Intravenous Drug Administration];succimer/po [Oral Drug Administration];succimer/pk [Pharmacokinetics];succimer/pd [Pharmacology];tetraethylenetetraamine/ae [Adverse Drug Reaction];tetraethylenetetraamine/do [Drug Dose];tetraethylenetetraamine/dt [Drug Therapy];tetraethylenetetraamine/po [Oral Drug Administration];tetraethylenetetraamine/pk [Pharmacokinetics];tetraethylenetetraamine/pd [Pharmacology];unclassified drug;unithiol/ae [Adverse Drug Reaction];unithiol/an [Drug Analysis];unithiol/cm [Drug Comparison];unithiol/dt [Drug Therapy];unithiol/po [Oral Drug Administration];unithiol/pk [Pharmacokinetics];unithiol/pd [Pharmacology];zinc trisodium pentetic acid/an [Drug Analysis];zinc trisodium pentetic acid/cm [Drug Comparison];zinc trisodium pentetic acid/do [Drug Dose];zinc trisodium pentetic acid/dt [Drug Therapy];zinc trisodium pentetic acid/to [Drug Toxicity];zinc trisodium pentetic acid/ih [Inhalational Drug Administration];zinc trisodium pentetic acid/im [Intramuscular Drug Administration];zinc trisodium pentetic acid/iv [Intravenous Drug Administration];zinc trisodium pentetic acid/pa [Parenteral Drug Administration];zinc trisodium pentetic acid/pk [Pharmacokinetics];zinc trisodium pentetic acid/pd [Pharmacology],"Flora, S. J. S.;Pachauri, V.",2010,July,http://dx.doi.org/10.3390/ijerph7072745,0,0,
1780,Cognitive profile and structural findings in Wilson's disease: A neuropsychological and MRI-based study,"Background: Systematic studies on neuropsychological profile in patients with Wilson's disease (WD) are far and few. Aim: To examine the profile of cognitive deficits and their magnetic resonance imaging (MRI) findings in patients with WD. Patients and Methods: Twelve confirmed patients of WD (age at onset and evaluation, 13.7+/-11.2 and 21.7+/-5.3 years, respectively; M-F ratio, 7:5) on de-coppering therapy constituted the study sample. Battery of neuropsychological tests measuring mental speed, motor speed, sustained attention, focused attention, verbal category fluency, verbal working memory, response inhibition, planning, concept formation, set-shifting ability, verbal and visual learning and memory were administered. Phenotypic details and observations on MRI of brain carried out within six months of neuropsychological assessment were documented. Results: Neuropsychological assessment elicited cognitive deficits in multiple domains in all but one patient, who had normal MRI. Percentage of patients in the deficit range in various domains included: motor speed: 73%; verbal working memory, sustained and focused attention: 50%; verbal learning: 42%; visuo-constructive ability, verbal memory, mental speed: 33%-34%; verbal fluency, set-shifting ability, visual memory, verbal memory: 25%-27%; and verbal recognition: 17%. MRI was normal in three patients, and revealed variable abnormalities in the remaining: cerebral atrophy in 3; brainstem atrophy in 2; signal changes in basal ganglia in 9; and brainstem signal changes in 5. None had subcortical white matter changes. Two patients with normal MRI showed cognitive deficits. Conclusion: This study provides insight into the complex cognitive and brain changes observed on MRI in WD. Use of advanced MRI techniques in a larger cohort may improve understanding regarding functional and structural brain changes observed in similar disorders.",Cognitive deficits;mri;neuropsychology;Wilson's disease;adolescent;adult;article;attention;brain atrophy/di [Diagnosis];clinical article;cognitive defect/di [Diagnosis];cross-sectional study;female;human;learning;male;memory;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;psychologic assessment;Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;penicillamine/dt [Drug Therapy];trihexyphenidyl;zinc sulfate/dt [Drug Therapy],"Hegde, S.;Sinha, S.;Rao, S. L.;Taly, A. B.;Vasudev, M. K.",2010,September-October,http://dx.doi.org/10.4103/0028-3886.72172,0,0,
1781,Diagnosis and management of acute liver failure,"Purpose of Review: Acute liver failure (ALF) is a devastating syndrome afflicting previously healthy individuals. Early recognition of the illness is crucial, as aggressive treatment may improve outcomes. Despite significant advances in care, however, the mortality remains high (30-100%). This brief review will focus on the causes and overall management of the complications of ALF. Recent Findings: Our knowledge of the causes of ALF has expanded significantly in the last decade. The mechanism of hepatic encephalopathy and cerebral edema in this setting continues to be elucidated and is discussed here. Summary: Improved outcomes can be achieved with the early recognition and aggressive management of ALF. © 2010 Wolters Kluwer Health Lippincott Williams & Wilkins.",Acetaminophen;Acute liver failure;Encephalopathy;Liver transplantation;acute lung injury;autoimmune hepatitis;blood clotting disorder;brain disease/dt [Drug Therapy];brain disease/pc [Prevention];brain edema;clinical trial;gastrointestinal hemorrhage/dt [Drug Therapy];hepatic encephalopathy;hepatitis B/dt [Drug Therapy];herpes simplex/dt [Drug Therapy];human;hypoglycemia;kidney failure;liver failure/co [Complication];liver failure/dt [Drug Therapy];liver failure/th [Therapy];liver toxicity/dt [Drug Therapy];liver toxicity/pc [Prevention];liver toxicity/si [Side Effect];liver toxicity/th [Therapy];lung hemodynamics;mushroom poisoning/dt [Drug Therapy];nonhuman;pregnancy;review;sepsis;thrombocytopenia;virus hepatitis;Wilson disease/dt [Drug Therapy];acetylcysteine/ct [Clinical Trial];acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];aciclovir/dt [Drug Therapy];aciclovir/iv [Intravenous Drug Administration];antacid agent/dt [Drug Therapy];antacid agent/iv [Intravenous Drug Administration];electrolyte;entecavir/dt [Drug Therapy];lamivudine/ct [Clinical Trial];lamivudine/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];paracetamol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];penicillin G/ct [Clinical Trial];penicillin G/dt [Drug Therapy];silibinin/ct [Clinical Trial];silibinin/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Larson, A. M.",2010,May,http://dx.doi.org/10.1097/MOG.0b013e32833847c5,0,0,
1782,Reply,,drug efficacy;drug screening;genetic disorder;in vitro study;letter;liver disease;priority journal;Wilson disease;copper;curcumin;penicillamine;trientine;Wilson disease protein;zinc,"Van Den Berghe, P. V. E.;Houwen, R. H. J.;Klomp, L. W. J.",2010,June,http://dx.doi.org/10.1002/hep.23705,0,0,
1783,Clinical application of liver MR imaging in Wilson's disease,"Objective: To determine whether there is a correlation between liver MR findings and the clinical manifestations and severity of liver dysfunction in patients with Wilson's disease. Materials and Methods: Two radiologists retrospectively evaluated MR images of the liver in 50 patients with Wilson's disease. The Institutional Review Board approved this retrospective study and informed consent was waived. MR images were evaluated with a focus on hepatic contour abnormalities and the presence of intrahepatic nodules. By using Fisher's exact test, MR findings were compared with clinical presentations (neurological and non-neurological) and hepatic dysfunction, which was categorized by the Child-Pugh classification system (A, B and C). Follow-up MR images were available for 17 patients. Results: Contour abnormalities of the liver and intrahepatic nodules were observed in 31 patients (62%) and 25 patients (50%), respectively. Each MR finding showed a statistically significant difference (p < 0.05) among the three groups of Child-Pugh classifications (A, n = 36; B, n = 5; C, n = 9), except for splenomegaly (p = 0.243). The mean age of the patients with positive MR findings was higher than that of patients with negative MR findings. For patients with Child-Pugh class A (n = 36) with neurological presentation, intrahepatic nodules, surface nodularity, and gallbladder fossa widening were more common. Intrahepatic nodules were improved (n = 8, 47%), stationary (n = 5, 29%), or aggravated (n = 4, 24%) on follow-up MR images. Conclusion: MR imaging demonstrates the contour abnormalities and parenchymal nodules of the liver in more than half of the patients with Wilson's disease, which correlates with the severity of hepatic dysfunction and clinical manifestations.",Hepatolenticular degeneration;Liver;Magnetic resonance (MR);adolescent;adult;article;child;child pugh classification;clinical article;clinical feature;controlled study;disease classification;disease severity;female;gallbladder;hepatography;human;image analysis;liver dysfunction/di [Diagnosis];liver nodule;liver parenchyma;male;neurologic disease;nuclear magnetic resonance imaging;preschool child;retrospective study;school child;splenomegaly;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Cheon, J. E.;Kim, I. O.;Seo, J. K.;Ko, J. S.;Lee, J. M.;Shin, C. I.;Kim, W. S.;Yeon, K. M.",2010,November/December,http://dx.doi.org/10.3348/kjr.2010.11.6.665,0,0,
1784,Chelation therapies: A chemical and biochemical perspective,"Chelation therapy occupies a central place in modern medicine and pharmacology, because continuous studies with laboratory animals and extensive clinical experience demonstrate that acute or chronic intoxications with a variety of metals can be considerable improved by administration of a suitable chelating agent. In this review the chemical characteristics, properties and uses of the most common chelating agents as well as those of some new and very promising agents of this type, are discussed. In the second part of the review the biological and biochemical impact of these agents, as well as their use for the treatment of some selected diseases and disorders, are also analyzed and discussed in detail. © 2010 Bentham Science Publishers Ltd.","Biological effects;Chelating agents;Chemical characteristics;Toxic metals;Alzheimer disease/dt [Drug Therapy];arsenic poisoning/dt [Drug Therapy];article;autoimmune disease/si [Side Effect];chelation therapy;complex formation;detoxification;drug hypersensitivity/si [Side Effect];drug indication;experimental animal;human;hypertension/si [Side Effect];hypocalcemia/si [Side Effect];injection site pain/si [Side Effect];intoxication/dt [Drug Therapy];iron overload/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];lung toxicity/si [Side Effect];mercurialism/dt [Drug Therapy];nephritis/si [Side Effect];nephrotoxicity/si [Side Effect];neurotoxicity/si [Side Effect];nonhuman;ototoxicity/si [Side Effect];patient compliance;structure activity relation;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];2,2 methylene di 8 quinolinol/pd [Pharmacology];cadmium/to [Drug Toxicity];calcium/to [Drug Toxicity];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];clioquinol/ae [Adverse Drug Reaction];clioquinol/dt [Drug Therapy];clioquinol/pd [Pharmacology];copper/to [Drug Toxicity];deferasirox/dt [Drug Therapy];deferasirox/po [Oral Drug Administration];deferasirox/pd [Pharmacology];deferiprone/dt [Drug Therapy];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/an [Drug Analysis];deferoxamine/dt [Drug Therapy];deferoxamine/pd [Pharmacology];deferoxamine/sc [Subcutaneous Drug Administration];dihydrolipoate/pd [Pharmacology];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/dt [Drug Therapy];dimercaprol/to [Drug Toxicity];dimercaprol/im [Intramuscular Drug Administration];dimercaprol/pd [Pharmacology];edetic acid/ae [Adverse Drug Reaction];edetic acid/dt [Drug Therapy];edetic acid/iv [Intravenous Drug Administration];edetic acid/pd [Pharmacology];iron/to [Drug Toxicity];lead/to [Drug Toxicity];magnesium/to [Drug Toxicity];manganese/to [Drug Toxicity];mercury/to [Drug Toxicity];metal derivative;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology];succimer/dt [Drug Therapy];succimer/to [Drug Toxicity];succimer/po [Oral Drug Administration];succimer/pa [Parenteral Drug Administration];succimer/pd [Pharmacology];thioctic acid/an [Drug Analysis];thioctic acid/po [Oral Drug Administration];thioctic acid/pd [Pharmacology];thorium/to [Drug Toxicity];unclassified drug;unithiol/to [Drug Toxicity];unithiol/po [Oral Drug Administration];unithiol/pa [Parenteral Drug Administration];unithiol/pd [Pharmacology];uranium/to [Drug Toxicity];vanadium/to [Drug Toxicity];zinc/to [Drug Toxicity]","Baran, E. J.",2010,November,http://dx.doi.org/10.2174/092986710793213760,0,0,
1785,Adjunctive vitamin E treatment in Wilson disease and suggestions for future trials: Reply,,adjuvant therapy;apoptosis;cystic fibrosis;human;letter;liver cell;liver injury;monotherapy;oxidative stress;priority journal;vitamin supplementation;Wilson disease/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];Fas antigen;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Houwen, R. H. J.;Linn, F. H. H.;Van Erpecum, K. J.",2010,May,http://dx.doi.org/10.1002/hep.23687,0,0,
1786,Biochemistry of zinc,"Zinc is an essential trace element to physiological functions of human organism. Over 300 enzymes have been shown to contain zinc as a cofactor. The zinc-deficient patients have severe dysfunction, mainly affecting T helper cells. Severe zinc deficiency is characterized by skin lesion. growth retardation, impaired wound healing, anemia, and mental retardation. Fortunately, all symptoms can be reversed by zinc treatment. Zinc reduces oxidative stress markers and generation of inflammatory cytokines. Besides, zinc plays a significant role in Parkinson's disease (PD). multiple sclerosis (MS), Alzheimer's disease (AD) and Wilson's disease (WD). It is also involved in signal transduction and apoptosis, i.e. zinc prevents prostate cells from growing by its induction of apoptosis. Many transcription factors contain zinc finger and similar structural motifs. Zinc finger motifs bind to a wide variety of compounds, such as nucleic acids, proteins and small molecules. Besides, zinc is a modulator of synaptic transmission in the central nervous system.",acrodermatitis enteropathica;anemia;antiinflammatory activity;antioxidant activity;apoptosis;article;catalysis;common cold/dt [Drug Therapy];growth retardation;human;immunopathology;infantile diarrhea/dt [Drug Therapy];liver toxicity/dt [Drug Therapy];liver toxicity/pc [Prevention];mental deficiency;neuromodulation;oxidative stress;Parkinson disease;signal transduction;skin disease;synaptic transmission;visual disorder;Wilson disease/dt [Drug Therapy];wound healing;zinc deficiency;alcohol dehydrogenase/ec [Endogenous Compound];carbonate dehydratase/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];manganese superoxide dismutase/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound];zinc/pd [Pharmacology],"Pasternak, K.;Horecka, A.;Kocot, J.",2010,,,0,0,
1787,Hemochromatosis and Wilson disease. [German],"Hereditary hemochromatosis and Wilson disease are both autosomal recessively inherited metabolic diseases that can lead to liver cirrhosis. Hereditary hemochromatosis is characterized by iron overload due to elevated duodenal iron absorption, while copper overload in Wilson disease results from an impaired copper excretion into bile. Especially in hemochromatosis but also in Wilson disease, the last decade has seen extraordinary growth in our understanding of the pathophysiology of both diseases. In hemochromatosis, hepatic and extrahepatic symptoms can occur. Extrahepatic symptoms include cardiomyopathy, diabetes mellitus, arthritis, and endocrine dysfunction. In Wilson disease, hepatic and/or neuropsychiatric symptoms are typical. While genetic testing for a homozygote HFE C282Y mutation (or a compound heterozygote C282Y/H63D mutation) is very helpful in hemochromatosis, genetic analysis of the Wilson gene, ATP7B, is limited by the existence of a plethora of individual mutations. Hemochromatosis is treated effectively with phlebotomies, whereas Wilson disease is treated medically with chelators (D-penicillamine and triethylenetetramine) or zinc salts. Liver transplantation is a therapeutic option for both diseases and shows excellent long-term results in Wilson disease, but less favorable results in hemochromatosis. The prognosis of sufficiently treated disease is very good for both diseases, especially when the diagnosis is established early in the disease course. © 2009 Springer Medizin Verlag.",Hemochromatosis;HFE gene;Liver cirrhosis;Metabolic liver disease;Wilson disease;arthritis;ATP7B gene;autosomal recessive inheritance;bile flow;c282y gene;cardiomyopathy;diabetes mellitus;duodenum;early diagnosis;endocrine disease;gene;gene mutation;genetic analysis;h63d gene;hemochromatosis/su [Surgery];hemochromatosis/th [Therapy];heterozygote;HFEC282Y gene;homozygote;human;iron absorption;iron overload;liver cirrhosis/co [Complication];liver transplantation;phlebotomy;prognosis;review;symptom;treatment indication;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];copper;iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Merle, U.;Weiss, K. H.;Stremmel, W.",2010,January,http://dx.doi.org/10.1007/s11377-009-0343-x,0,0,
1788,The role of garlic in hepatopulmonary syndrome: A randomized controlled trial,"BACKGROUND: Increased nitric oxide production in cirrhosis has been commonly implicated in the genesis of hepatopulmonary syndrome (HPS). Initial studies suggested that garlic, a constituent of the daily diet, may have a role in the treatment of HPS by altering nitric oxide production. OBJECTIVE: To evaluate the effects of oral garlic supplementation on arterial blood gas parameters, and overall morbidity and mortality in patients with HPS. METHODS: Twenty-one and 20 HPS patients were randomly assigned to receive either oral garlic supplementation or placebo, respectively, and were evaluated monthly over a period of nine to 18 months. RESULTS: After nine months, garlic supplementation was associated with a 24.66% increase in baseline arterial oxygen levels (83.05 mmHg versus 66.62 mmHg; P<0.001), compared with only a 7.37% increase (68.75 mmHg versus 64.05 mmHg; P=0.02) among subjects in the placebo group. There was also a 28.35% decrease in alveolar-arterial oxygen gradient (21.35 mmHg versus 29.77 mmHg; P<0.001) among patients with HPS who received garlic, in contrast with only a 10.73% decrease (29.11 mmHg versus 32.61 mmHg; P=0.12) among those in the placebo group. After nine months, the arterial oxygen level was significantly higher (83.05 mmHg versus 68.75 mmHg; P<0.001) and the alveolar-arterial oxygen gradient was significantly lower (21.35 mmHg versus 29.11 mmHg; P<0.001) among patients receiving garlic compared with those receiving placebo. Reversal of HPS was observed in 14 of 21 patients (66.67%) on garlic supplementation (intent-to-treat analysis) and in one of 20 patients (5%) on placebo. Two of 21 patients undergoing garlic supplementation died during follow-up in contrast to seven of 20 patients who were on placebo. CONCLUSIONS: Garlic supplementation may be beneficial in patients with HPS for the reversal of intrapulmonary shunts as well as reducing hypoxemia and mortality. ©2010 Pulsus Group Inc. All rights reserved.",Duration of disease;Garlic;Hepatopulmonary syndrome;Incomplete syndrome;Mortality;adult;alcohol liver disease;arterial gas;arterial oxygen saturation;arterial oxygen tension;article;autoimmune disease/dt [Drug Therapy];blood gas parameters;clinical trial;controlled clinical trial;controlled study;esophagus varices bleeding/dt [Drug Therapy];esophagus varices bleeding/pc [Prevention];female;follow up;hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];hepatopulmonary syndrome/dt [Drug Therapy];hepatopulmonary syndrome/co [Complication];human;hypoxemia;liver disease/dt [Drug Therapy];lung alveolus oxygen tension;major clinical study;male;morbidity;portal hypertension;priority journal;pulmonary shunt;randomized controlled trial;Wilson disease/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];herbaceous agent/ct [Clinical Trial];herbaceous agent/dt [Drug Therapy];herbaceous agent/po [Oral Drug Administration];placebo;prednisolone/dt [Drug Therapy];spironolactone/dt [Drug Therapy];zinc/dt [Drug Therapy],"De, B. K.;Dutta, D.;Pal, S. K.;Gangopadhyay, S.;Baksi, S. D.;Pani, A.",2010,March,,0,0,
1789,Current state of Wilson disease patients in central Japan,"Objective This study evaluated the current state of patients with Wilson disease in central Japan. Patients and Methods Between 1999 and 2007, 30 patients were diagnosed as having Wilson disease withan International Diagnostic Score of 4 or more. The phenotypes, genotypes and post-diagnostic courses of these patients were analyzed. Results Twenty-six patients had ATP7B mutations responsible for Wilson disease. Four patients had a single mutant chromosome. There were 2 major mutations of 2333 G>T and 2871 delC (40%), and 6 novel mutations (13%) in our patients. The first clinical manifestation was the hepatic form in 22, neurological form in 5, and hemolysis in 3 patients. The hepatic form was diagnosed around the age of 13 years, followed by neurological complication with a time lag of 9 years. Thus, some patients, especially patients with the neurological form, did not undergo early diagnostic tests including ATP7B analysis. During the post-diagnosis period, 3 patients were hospitalized for recurrent liver disease, and 2 patients committed suicide. One female patient died from acute hepatic failure associated with encephalopathy after fertilization therapy, while 2 male patients recovered from encephalopathy-free, prolonged hepatic failure after noncompliance with drug therapy. The King's Scores for liver transplantation were below the cut-off in both cases. Conclusion To minimize delayed diagnosis, ceruloplasmin determination and ATP7B analysis may be recommended to patients showing hepatic damage of unknown etiology. At gene diagnosis, appropriate management of patients including compliance education and emotional care to prevent suicide might be important. 2010 The Japanese Society of Internal Medicine. © 2010 The Japanese Society of Internal Medicine.",Atp7b;Copper chelation;Hepatic failure;Suicide;adolescent;adult;article;ascites/dt [Drug Therapy];brain disease;chromosome aberration;clinical article;clinical feature;delayed diagnosis;disease association;disease course;early diagnosis;emotionality;female;gene mutation;genotype;hemolysis;hospitalization;human;International Classification of Diseases;international diagnostic score;Japan;liver disease;liver failure;male;neurologic disease;patient attitude;patient care;patient education;phenotype;protein analysis;recurrent disease;suicide attempt;Wilson disease/dt [Drug Therapy];albumin/dt [Drug Therapy];ceruloplasmin;penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Tatsumi, Y.;Hattori, A.;Hayashi, H.;Ikoma, J.;Kaito, M.;Imoto, M.;Wakusawa, S.;Yano, M.;Hayashi, K.;Katano, Y.;Goto, H.;Okada, T.;Kaneko, S.",2010,April 30,http://dx.doi.org/10.2169/internalmedicine.49.2931,0,0,
1790,Movement disorders and pregnancy: A review of the literature,"Pregnant patients are rarely encountered in the movement disorders clinic, but they present significant dilemmas regarding treatment and counseling for neurologists. While movement disorders in pregnancy once described those disorders arising de novo during pregnancy, such as chorea gravidarum or restless leg syndrome, advancing maternal age in Western countries will likely increase the number of women in whom pregnancy complicates a pre-existing movement disorder. Physicians treating these women must be aware of the impact of the movement disorder and its treatment on fertility, pregnancy, fetal development, lactation, and infant care. This review summarizes retrospective series and case reports to both guide clinicians and to stimulate and direct the design of prospective studies. © 2010 Movement Disorder Society.",Chorea gravidarum;Parkinson's disease;Pregnancy;Teratogenicity;Wilson's disease;ataxia/et [Etiology];brain depth stimulation;child care;chorea/co [Complication];chorea/dt [Drug Therapy];chorea/et [Etiology];deep vein thrombosis/si [Side Effect];drug contraindication;drug megadose;drug safety;dyskinesia/si [Side Effect];dystonia/co [Complication];dystonia/dt [Drug Therapy];dystonia/et [Etiology];dystonia/si [Side Effect];dystonia/th [Therapy];essential tremor/co [Complication];extrapyramidal symptom/si [Side Effect];fertility;fetus development;Friedreich ataxia;Gilles de la Tourette syndrome/co [Complication];Gilles de la Tourette syndrome/dt [Drug Therapy];Gilles de la Tourette syndrome/et [Etiology];human;Huntington chorea/dt [Drug Therapy];lactation;lung embolism/si [Side Effect];maternal age;motor dysfunction/co [Complication];motor dysfunction/et [Etiology];nausea/dt [Drug Therapy];nonhuman;oculogyric crisis/si [Side Effect];opisthotonus/si [Side Effect];orofacial dyskinesia/si [Side Effect];Parkinson disease/dt [Drug Therapy];parkinsonism/co [Complication];parkinsonism/dt [Drug Therapy];preeclampsia/dt [Drug Therapy];priority journal;respiratory tract disease/et [Etiology];respiratory tract disease/si [Side Effect];restless legs syndrome/et [Etiology];review;tic/co [Complication];tic/dt [Drug Therapy];tic/et [Etiology];torticollis/si [Side Effect];vomiting/dt [Drug Therapy];weakness/et [Etiology];weakness/si [Side Effect];Wernicke encephalopathy/dt [Drug Therapy];Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];withdrawal seizure/et [Etiology];withdrawal seizure/si [Side Effect];baclofen/ae [Adverse Drug Reaction];baclofen/dt [Drug Therapy];baclofen/tl [Intrathecal Drug Administration];baclofen/po [Oral Drug Administration];benserazide/dt [Drug Therapy];botulinum toxin A/dt [Drug Therapy];botulinum toxin B/dt [Drug Therapy];cabergoline/dt [Drug Therapy];carbidopa/dt [Drug Therapy];chlorpromazine/dt [Drug Therapy];clonazepam/dt [Drug Therapy];dopamine receptor blocking agent/ae [Adverse Drug Reaction];dopamine receptor blocking agent/dt [Drug Therapy];fluoxetine/cb [Drug Combination];fluoxetine/dt [Drug Therapy];haloperidol/ae [Adverse Drug Reaction];haloperidol/dt [Drug Therapy];levodopa/dt [Drug Therapy];magnesium sulfate/ae [Adverse Drug Reaction];magnesium sulfate/dt [Drug Therapy];metoclopramide/ae [Adverse Drug Reaction];metoclopramide/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pergolide/dt [Drug Therapy];pimozide/cb [Drug Combination];pimozide/dt [Drug Therapy];pramipexole/dt [Drug Therapy];prochlorperazine/ae [Adverse Drug Reaction];prochlorperazine/dt [Drug Therapy];prochlorperazine/pd [Pharmacology];progesterone/dt [Drug Therapy];promethazine/ae [Adverse Drug Reaction];promethazine/dt [Drug Therapy];reserpine/to [Drug Toxicity];reserpine/pd [Pharmacology];selegiline/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];thiamine/dt [Drug Therapy];thiamine/iv [Intravenous Drug Administration];trientine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy],"Kranick, S. M.;Mowry, E. M.;Colcher, A.;Horn, S.;Golbe, L. I.",2010,30 Apr,http://dx.doi.org/10.1002/mds.23071,0,0,
1791,Wilson disease and its current problems,,Compliance;Suicide;Wilson disease;clinical effectiveness;copper metabolism;depression;disease severity;editorial;functional status;hopelessness;human;liver cell;liver failure;liver transplantation;living donor;patient attitude;patient compliance;patient education;protein expression;suicide attempt/pc [Prevention];treatment outcome;treatment withdrawal;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];copper;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy],"Harada, M.",2010,April 30,http://dx.doi.org/10.2169/internalmedicine.49.3380,0,0,
1792,Electroencephalography in stable therapeutic phase of Wilson's disease. [German],"Introduction: Wilson's disease is a rare autosomal recessive disorder of the copper metabolism. In addition to hepatic and extrapyramidal motor clinical symptoms, patients with Wilson's disease also exhibit subclinical disorders of other central nervous pathways. The reports on abnormalities detected in EEG recordings are inconsistent and infrequent. Methods: In this study, electroencephalography was performed on 49 patients with Wilson's disease (32 patients with the neurological form, 17 patients with the non-neurological form) undergoing long-term drug therapy. Attention was paid to general slowing, focal abnormalities and epileptiform activity. The EEG results were correlated to the clinical manifestations by means of a neurology score established for Wilson's disease. Results: The EEG recordings presented normal results in almost 80% of all investigated patients presenting with the long-term course of the disease. A mild, continuous slow activity occurred in six patients and intermittent rhythmic delta activity was seen in two patients with the neurological form of Wilson's disease. A difference in the median alpha-rhythm frequency between the neurological and non-neurological form (9.27/s and 9.63/s, respectively) was insignificant. Epileptiform activity was detected only in one patient with coincidental epilepsy. Conclusions: Patients with Wilson's disease show normalised electroencephalographic traces in the course of the disease. Abnormal changes seem to be due to either additional disturbances or secondary complications. In this respect, electroencephalography has proven helpful primarily in differential diagnostics performed over the course of the disease. © 2010 Georg Thieme Verlag KG.",eeg;electroencephalography;Wilson's disease;adult;aged;alpha rhythm;article;clinical article;delta rhythm;differential diagnosis;disease course;EEG abnormality/di [Diagnosis];epileptic discharge;female;human;male;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc derivative/cb [Drug Combination];zinc derivative/dt [Drug Therapy],"Gunther, P.;Baum, P.;Villmann, T.;Hermann, W.",2010,,http://dx.doi.org/10.1055/s-0030-1253441,0,0,
1793,"Wilson's disease in children and adolescents: Diagnosis and treatment. [Portuguese, English]","Objective: To describe clinical symptoms, laboratory findings at diagnosis and treatment of children and adolescents with Wilson's disease. Methods: This is a descriptive and retrospective study of a series of 17 children and adolescents with Wilson's disease, assited at the Pediatric Hepatology Ambulatory of the Hospital das Clinicas of Universidade Federal de Minas Gerais, Brazil, from 1985 to 2008. Data were collected by revision of medical charts and during clinical follow-up. Results: Patients were 2.8 to 15.1 years old, with a mean age of 8.8+/-0.9 years. The disease main presentation was hepatic (53%), followed by the asymptomatic form, diagnosed by family screening. The Kayser-Fleischer ring was observed in 41% of the patients. The ceruloplasmin was altered in 15 out of 17 patients, and the urinary copper varied from 24 to 1000mcg/24h (median: 184mcg/24h). The treatment was stablished with D-penicillamine in all cases. Slight side effects were observed in five children, with no need to interrupt or change medication. Clinical and laboratory responses to treatment, with normalization of aminotransferases levels, were shown in 14 patients after a median of 10.7 months. Although treated, three patients died (one due to fulminant hepatitis and two due to severe hepatic failure). Conclusions: Wilson's disease is rare in the pediatric group. In children, the main presentation is the liver disease. The diagnosis can be established by reduced ceruloplasmin levels and elevated copper excretion in the 24-hour urine, but it demands high suspicion level. There are good tolerance and response to medical treatment.",Child;Hepatic insufficiency;Hepatolenticular degeneration;Wilson's disease;acute hepatitis;adolescent;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;bilirubin blood level;ceruloplasmin blood level;chronic hepatitis;clinical article;copper liver level;copper urine level;descriptive research;disease severity;family;fatty liver;female;hepatitis;hepatosplenomegaly;human;kayser fleischer ring;liver failure;liver fibrosis;liver level;male;mortality;nausea and vomiting/si [Side Effect];proteinuria/si [Side Effect];retrospective study;screening;symptom;treatment response;unspecified side effect/si [Side Effect];urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Socio, S. D. A.;Ferreira, A. R.;Fagundes, E. D. T.;Roquete, M. L. V.;Pimenta, J. R.;Campos, L. D. F.;Penna, F. J.",2010,June,,0,0,
1794,The current status and new advances in diagnosis and treatment of Wilson disease,"Wilson disease is an inherited, autosomal recessive, copper accumulation and toxicity disorder that affects about 30 individuals per million. This rare disease is caused by mutations in the gene encoding a copper-transporting P-type ATPase, which is important for copper excretion into bile, leading to copper accumulation in the liver. Toxic copper concentrations can also be found in the brain and kidney, and clinical phenotypes include hepatic, haemolytic, neurologic and psychiatric diseases. Diagnosis is based on the combination of clinical features and findings such as increased urinary copper excretion, reduced levels of serum ceruloplasmin, high concentrations of copper in liver tissuesand Kayser-Fleischer rings, biochemical and immunological markers,magnetic resonance imaging neuropathological study. Genetic studies are also becoming available for clinical use, but the utility of direct mutation analysis is limited.",Diagnosis and treatment;New advances;Wilson disease;abdominal pain;acute hepatitis/si [Side Effect];aggression;amylase blood level;anemia/si [Side Effect];anxiety;aplastic anemia/si [Side Effect];arthropathy/si [Side Effect];ataxia;autosomal recessive inheritance;bone marrow depression/si [Side Effect];bone marrow toxicity/si [Side Effect];bone radiography;bradykinesia;brain;cardiomyopathy;central nervous system malformation/si [Side Effect];ceruloplasmin blood level;cholestasis/si [Side Effect];cholesterol blood level;clinical feature;computer assisted tomography;contracture/si [Side Effect];copper blood level;corticosteroid therapy;cutis laxa/si [Side Effect];delusion;depression;drug eruption/si [Side Effect];drug fever/si [Side Effect];drug withdrawal;dyskinesia;elastosis perforans serpiginosa/si [Side Effect];electroencephalogram;gene mutation;genetic variability;Goodpasture syndrome/si [Side Effect];hallucination;human;hypoparathyroidism;incidence;irritability;jaundice;kidney;kidney tubule acidosis;liver;liver cirrhosis;liver transplantation;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];micrognathia/si [Side Effect];morning dosage;muscle rigidity;myasthenia gravis/si [Side Effect];nausea;nephrotic syndrome/si [Side Effect];neuroimaging;neuropathology;neutropenia/si [Side Effect];nuclear magnetic resonance imaging;paranoia;pathophysiology;proteinuria/si [Side Effect];pyridoxine deficiency/dt [Drug Therapy];pyridoxine deficiency/pc [Prevention];review;side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];skin disease/si [Side Effect];splenectomy;stomach irritation/si [Side Effect];thrombocytopenia/si [Side Effect];tremor;triacylglycerol blood level;triacylglycerol lipase blood level;urinary excretion;vomiting;Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];amylase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];corticosteroid;Menkes protein/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];tetrathiomolybdate ammonium;tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/dt [Drug Therapy];triacylglycerol lipase/ec [Endogenous Compound];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy],"Kiranmayi, G. V. N.;Ravi Shankar, K.;Chandrasekhar Nainala, V.",2010,December,,0,0,
1795,Wilson's disease: Current concepts in diagnosis and management. [Croatian],"Wilson's disease is a rare autosomal recessive disorder of copper transport resulting in copper accumulation in the liver, brain and cornea. The incidence is estimated to be 1:30000-80000 in most populations. The Wilson disease gene, now designated ATP7B, situated on 13<sup>th</sup> chromosome (13q14.3), was cloned in 1993. The clinical phenotypes include hepatic, neurologic and psychiatric diseases, or a combination of these. A combination of clinical features, various laboratory parameters and Kayser-Fleischer rings is necessary for making the diagnosis. Mutation analysis may provide definitive diagnosis and is becoming part of diagnostic algorithm, especially in patients with indeterminate clinical and biochemical features. Family screening of first-degree relatives should be undertaken. Recognition of the disease at an early stage is crucial because treatment prevents severe liver damage and/or lifelong neurologic disabilities. The aim of treatment is reduction of tissue copper concentration either by enhancing its urinary excretion or by decreasing its intestinal absorption. Treatment includes copper-chelators, such as penicillamine and trientine as well as zinc salts. Liver transplantation is treatment option in cases of acute liver failure or treatment-resistant and severe advanced liver disease. It is not indicated in patients with mainly neuropsychiatric presentation.",Diagnosis;Therapy;Wilson's disease;abnormal laboratory result;acute liver failure/co [Complication];acute liver failure/su [Surgery];clinical feature;disease severity;early diagnosis;family history;gene mutation;genetic analysis;human;liver disease/pc [Prevention];liver transplantation;neurologic disease/pc [Prevention];review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Kalauz, M.;Telarovic, S.;Ljubic, H.",2010,,,0,0,
1796,Appendiceal orifice inflammation in an 8-year-old girl with ulcerative colitis complicating Wilson's disease,"Appendiceal orifice inflammation (AOI) may occur as a skipped lesion in ulcerative colitis (UC). Cases of ulcerative colitis complicated by Wilson's disease have also been reported. We report herein a case of AOI that occurred as a missed lesion in an 8-year-old girl with UC complicating Wilson's disease, which is rare in children.",Child;Hepatolenticular degeneration;Inflammatory bowel disease;Orifice of appendix;Ulcerative colitis;abdominal pain;appendic orifice inflammation/dt [Drug Therapy];appendix disease/di [Diagnosis];appendix disease/dt [Drug Therapy];appendix orifice inflammation/dt [Drug Therapy];appendix orifice inflammation/di [Diagnosis];article;case report;colonoscopy;drug dose increase;drug substitution;drug withdrawal;female;hematochezia;human;loose feces;rectum biopsy;school child;ulcerative colitis/co [Complication];ulcerative colitis/dt [Drug Therapy];unspecified side effect/si [Side Effect];weight reduction;Wilson disease;enema;mesalazine/dt [Drug Therapy];mesalazine/po [Oral Drug Administration];mesalazine/rc [Rectal Drug Administration];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction],"Jang, H. J.;Jang, J. Y.;Kim, K. M.",2010,March,http://dx.doi.org/10.5009/gnl.2010.4.1.126,0,0,
1797,HFE gene mutations and Wilson's disease in Sardinia,"Background: Hypocaeruloplasminaemia can lead to tissue iron storage in Wilson's disease and the possibility of iron overload in long-term overtreated patients should be considered. The HFE gene encodes a protein that is intimately involved in intestinal iron absorption. Aims: The aim of this study was to determine the prevalence of the HFE gene mutation, its role in iron metabolism of Wilson's disease patients and the interplay of therapy in copper and iron homeostasis. Methods: The records of 32 patients with Wilson's disease were reviewed for iron and copper indices, HFE gene mutations and liver biopsy. Results: Twenty-six patients were negative for HFE gene mutations and did not present significant alterations of iron metabolism. The HFE mutation was significantly associated with increased hepatic iron content (P < 0.02) and transferrin saturation index (P < 0.03). After treatment period, iron indices were significantly decreased only in HFE gene wild-type. Conclusions: The HFE gene mutations may be an addictional factor in iron overload in Wilson's disease. Our results showed that an adjustment of dosage of drugs could prevent further iron overload induced by overtreatment only in patients HFE wild-type. © 2009.",Copper;Haemochromatosis gene;Iron overload;adult;article;clinical article;clinical feature;controlled study;copper metabolism;female;gene mutation;genetic analysis;genetic association;hemochromatosis/di [Diagnosis];homeostasis;human;human tissue;immunohistochemistry;iron absorption;iron metabolism;liver biopsy;liver function test;long term care;male;priority journal;wild type;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];HFE protein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];transferrin/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Sorbello, O.;Sini, M.;Civolani, A.;Demelia, L.",2010,March,http://dx.doi.org/10.1016/j.dld.2009.06.012,0,0,
1798,Risks of copper and iron toxicity during aging in humans,"Copper and iron are essential but also toxic metals. Their essentiality is known, but their toxicity, except for the genetic overload diseases, Wilson's disease and hemochromatosis, is not so well known. Yet, their toxicities are so general in the population that they are a looming public health problem in diseases of aging and in the aging process itself. Both metals are transition elements, and their resulting redox properties have been used during evolution in the development of oxidative energy generation. But both contribute to the production of excess damaging oxidant radicals. Evolution has kept stores of copper and iron in excess during the reproductive years because they are so vital to life. But the oxidant damage from these excess stores of metals builds up as we age, and natural selection ceases to act after about age 50 since diseases after that do not contribute to reproductive fitness. Diseases of aging such as Alzheimer's disease, other neurodegenerative diseases, arteriosclerosis, diabetes mellitus, and others may all be contributed to by excess copper and iron. A very disturbing study has found that in the general population those in the highest fifth of copper intake, if they are also eating a relatively high fat diet, lose cognition at over three times the normal rate. Inorganic copper in drinking water and in supplements is handled differently than food copper and is therefore more toxic. Trace amounts of copper in drinking water, less than one-tenth of that allowed in human drinking water by the Environmental Protection Agency, greatly enhanced an Alzheimer's-like disease in an animal model. In the last part of this review, I will provide advice on how to lower risks from copper and iron toxicity. © 2010 American Chemical Society.",aging;Alzheimer disease/et [Etiology];arteriosclerosis/et [Etiology];atherosclerosis/et [Etiology];blood level;cognitive defect/et [Etiology];degenerative disease/et [Etiology];diabetes mellitus/et [Etiology];environmental protection;evening dosage;fitness;food contamination;human;lipid diet;morning dosage;oxidation reduction reaction;oxidative stress;patient monitoring;public health problem;reproductive toxicity;review;risk assessment;risk factor;water contamination;Wilson disease/dt [Drug Therapy];copper/to [Drug Toxicity];drinking water;gluconate zinc;iron/to [Drug Toxicity];tetrathiomolybdic acid;zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc acetate,"Brewer, G. J.",2010,15 Feb,http://dx.doi.org/10.1021/tx900338d,0,0,
1799,Antifibrosis: To reverse the irreversible,"Fibrosis is a pathological process that includes scar formation and overproduction of extracellular matrix by the connective tissue as a response to tissue damage. The fibrotic process involves multiple organs and results in progressive life-threatening diseases. Today, we know more about the molecular mechanism that leads to fibrosis involving different type of cells, cytokines, chemokines, and tissue enzymes. Fibrosis was considered an irreversible process, at least clinically, and is still usually treated by anti-inflammatory and immunosuppressive agents. No proven antifibrotic therapy has shown efficacy in ameliorating the clinical course of fibrotic diseases, but our current understanding led to the development of different drugs with promising results, like: mycophenolate mofetil, interferon, relaxin, and intravenous immunoglobulin. This review will provide a glance to this heavily investigated subject. © Humana Press Inc. 2009.",Antifibrotic therapies;Fibroblast;Fibrosis;IVIg;Profibrotic cytokines;amyloidosis/dt [Drug Therapy];autoimmune disease/dt [Drug Therapy];bone marrow transplantation;breast cancer/dt [Drug Therapy];cardiac graft rejection/dt [Drug Therapy];cardiac graft rejection/pc [Prevention];chronic myeloid leukemia/dt [Drug Therapy];clinical trial;cytokine production;drug megadose;extracellular matrix;familial Mediterranean fever/dt [Drug Therapy];fibrosing alveolitis/dt [Drug Therapy];fibrosis/dt [Drug Therapy];fibrosis/pc [Prevention];fibrosis/th [Therapy];gout/dt [Drug Therapy];graft versus host reaction/dt [Drug Therapy];heart muscle fibrosis/dt [Drug Therapy];human;hypertrophic scar/dt [Drug Therapy];immune deficiency/dt [Drug Therapy];inflammatory disease/dt [Drug Therapy];interstitial lung disease/dt [Drug Therapy];kidney fibrosis/dt [Drug Therapy];kidney fibrosis/pc [Prevention];kidney graft rejection/dt [Drug Therapy];kidney graft rejection/pc [Prevention];liver cirrhosis/dt [Drug Therapy];liver fibrosis/dt [Drug Therapy];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];low drug dose;lung fibrosis/dt [Drug Therapy];myelofibrosis/dt [Drug Therapy];nematodiasis/dt [Drug Therapy];neoplasm/dt [Drug Therapy];nonhuman;pathogenesis;pericarditis/dt [Drug Therapy];peritoneum sclerosis/dt [Drug Therapy];primary biliary cirrhosis/dt [Drug Therapy];retroperitoneal fibrosis/dt [Drug Therapy];review;schistosomiasis/dt [Drug Therapy];scleroderma/dt [Drug Therapy];skin fibrosis/dt [Drug Therapy];skin fibrosis/pc [Prevention];stem cell transplantation;survival rate;systemic sclerosis/dt [Drug Therapy];viral gene therapy;Wilson disease/dt [Drug Therapy];acetylcysteine/ct [Clinical Trial];acetylcysteine/cb [Drug Combination];acetylcysteine/dt [Drug Therapy];adenovirus vector;azathioprine/ct [Clinical Trial];azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];bosentan/dt [Drug Therapy];captopril/dt [Drug Therapy];colchicine/ct [Clinical Trial];colchicine/dt [Drug Therapy];corticosteroid/ct [Clinical Trial];corticosteroid/cb [Drug Combination];corticosteroid/dt [Drug Therapy];cyclophosphamide/ct [Clinical Trial];cyclophosphamide/cb [Drug Combination];cyclophosphamide/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];dipeptidyl carboxypeptidase inhibitor/cb [Drug Combination];dipeptidyl carboxypeptidase inhibitor/dt [Drug Therapy];enalapril/dt [Drug Therapy];etanercept/ct [Clinical Trial];etanercept/dt [Drug Therapy];gamma1b interferon/ct [Clinical Trial];gamma1b interferon/cb [Drug Combination];gamma1b interferon/dt [Drug Therapy];hydroxymethylglutaryl coenzyme A reductase inhibitor/cb [Drug Combination];hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy];imatinib/dt [Drug Therapy];immunoglobulin/ct [Clinical Trial];immunoglobulin/dt [Drug Therapy];immunoglobulin/iv [Intravenous Drug Administration];interleukin 4 antibody/dt [Drug Therapy];interleukin 5 antibody/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester/ct [Clinical Trial];mycophenolic acid 2 morpholinoethyl ester/cb [Drug Combination];mycophenolic acid 2 morpholinoethyl ester/dt [Drug Therapy];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];pirfenidone/ct [Clinical Trial];pirfenidone/dt [Drug Therapy];placebo;prednisolone/cb [Drug Combination];prednisolone/dt [Drug Therapy];prednisone/ct [Clinical Trial];prednisone/cb [Drug Combination];prednisone/dt [Drug Therapy];recombinant relaxin/dt [Drug Therapy];relaxin/dt [Drug Therapy];relaxin/ec [Endogenous Compound];suramin/dt [Drug Therapy];tamoxifen/ct [Clinical Trial];tamoxifen/dt [Drug Therapy];transforming growth factor beta/ec [Endogenous Compound];unindexed drug,"Paz, Z.;Shoenfeld, Y.",2010,April,http://dx.doi.org/10.1007/s12016-009-8157-7,0,0,
1800,Liver disease in pregnancy,"Severe liver disease in pregnancy is rare. Pregnancy-related liver disease is the most frequent cause of liver dysfunction in pregnancy and provides a real threat to fetal and maternal survival. A rapid diagnosis differentiating between liver disease related and unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. Research has improved our understanding of the pathogenesis of pregnancy-related liver disease, which has translated into improved maternal and fetal outcomes. Here, we provide an overview of liver diseases that occur in pregnancy, an update on the key mechanisms involved in their pathogenesis, and assessment of available treatment options. © 2010 Elsevier Ltd. All rights reserved.",adrenal hyperplasia/si [Side Effect];biliary tract disease;bradycardia/si [Side Effect];Budd Chiari syndrome;cleft palate/si [Side Effect];congenital malformation/dt [Drug Therapy];differential diagnosis;eclampsia/et [Etiology];fetus lung maturation;fetus outcome;HELLP syndrome/et [Etiology];HELLP syndrome/su [Surgery];HELLP syndrome/th [Therapy];hepatitis A;hepatitis B/dt [Drug Therapy];hepatitis B/et [Etiology];hepatitis B/th [Therapy];hepatitis C/dt [Drug Therapy];hepatitis C/et [Etiology];hepatitis C/th [Therapy];human;hyperemesis gravidarum;hyperkalemia/si [Side Effect];hypertension/dt [Drug Therapy];hypoglycemia/si [Side Effect];immunoglobulin deficiency/si [Side Effect];intrahepatic cholestasis;intrauterine growth retardation/si [Side Effect];kidney failure/si [Side Effect];liver cirrhosis;liver disease/et [Etiology];liver disease/su [Surgery];liver disease/th [Therapy];liver failure;liver fatty degeneration/et [Etiology];liver hematoma;liver transplantation;low birth weight/si [Side Effect];lymphocytopenia/si [Side Effect];medical research;pathogenesis;portal hypertension;preeclampsia/et [Etiology];pregnancy;pregnancy outcome;premature fetus membrane rupture/si [Side Effect];premature labor/si [Side Effect];priority journal;pruritus/dt [Drug Therapy];rehydration;review;spontaneous abortion/dt [Drug Therapy];vitamin supplementation;Wernicke encephalopathy/dt [Drug Therapy];Wernicke encephalopathy/pc [Prevention];Wilson disease/dt [Drug Therapy];azathioprine/ae [Adverse Drug Reaction];azathioprine/to [Drug Toxicity];colestyramine/dt [Drug Therapy];cyclosporin A/ae [Adverse Drug Reaction];dexamethasone/cm [Drug Comparison];entecavir/dt [Drug Therapy];hydralazine/dt [Drug Therapy];labetalol/dt [Drug Therapy];lamivudine/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester/dt [Drug Therapy];nifedipine/dt [Drug Therapy];prednisolone/ae [Adverse Drug Reaction];propranolol/ae [Adverse Drug Reaction];tacrolimus/ae [Adverse Drug Reaction];tenofovir/dt [Drug Therapy];thiamine/dt [Drug Therapy];ursodeoxycholic acid/cm [Drug Comparison];zinc/dt [Drug Therapy],"Joshi, D.;James, A.;Quaglia, A.;Westbrook, R. H.;Heneghan, M. A.",2010,,http://dx.doi.org/10.1016/S0140-6736%2809%2961495-1,0,0,
1801,Psychiatric manifestations of wilson's disease and treatment with electroconvulsive therapy,"Wilson's disease is a rare genetic disorder involving the liver and brain, with onset frequently in adolescence. Psychiatric symptoms are often the first manifestation of the disease and can obscure the diagnosis. Although such patients are more commonly seen in neurological and hepatological settings, mental health professionals must keep in mind a high level of suspicion, once first presentations may be of psychiatric nature. We present the case of a 20-year-old female patient who initially presented with psychiatric symptoms. The neuropsychiatric manifestations and treatment of this patient with electroconvulsive therapy is presented.",Electroconvulsive therapy;Treatment;Wilson's disease;adult;article;brain atrophy/co [Complication];brain atrophy/di [Diagnosis];case report;ceruloplasmin blood level;clinical feature;copper blood level;disease course;echography;female;follow up;hepatosplenomegaly/co [Complication];hepatosplenomegaly/di [Diagnosis];human;mental disease/cn [Congenital Disorder];mental disease/di [Diagnosis];mental disease/dt [Drug Therapy];mental disease/th [Therapy];nuclear magnetic resonance imaging;patient compliance;slit lamp;treatment response;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];lorazepam/dt [Drug Therapy];lorazepam/po [Oral Drug Administration];olanzapine/cb [Drug Combination];olanzapine/dt [Drug Therapy];olanzapine/po [Oral Drug Administration];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration],"Sahoo, M. K.;Avasthi, A.;Sahoo, M.;Modi, M.;Biswas, P.",2010,Janauary 01,http://dx.doi.org/10.4103/0019-5545.58898,0,0,
1802,Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry,"Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn ""cancer-promoting"" copper into anti-cancer agents. © 2010 Bentham Science Publishers Ltd.","Angiogenesis;Copper;Oxidative stress;Proteasome inhibitor;ros;acne/si [Side Effect];aggressiveness;amebiasis/dt [Drug Therapy];anemia/si [Side Effect];article;bacterial infection/dt [Drug Therapy];blister/si [Side Effect];burn/si [Side Effect];chest tightness/si [Side Effect];clinical trial;constipation/si [Side Effect];diarrhea/si [Side Effect];drug blood level;drug excretion;drug half life;drug induced headache/si [Side Effect];drug structure;dyspnea/si [Side Effect];fever/si [Side Effect];glioblastoma/dt [Drug Therapy];glioblastoma/rt [Radiotherapy];glossitis/si [Side Effect];high throughput screening;human;hypertension/dt [Drug Therapy];leukopenia/si [Side Effect];liver cell carcinoma/dt [Drug Therapy];mouth inflammation/si [Side Effect];muscle weakness/si [Side Effect];mycosis/dt [Drug Therapy];neurologic disease/si [Side Effect];neurotoxicity/si [Side Effect];nonhuman;pruritus/si [Side Effect];rash/si [Side Effect];side effect/si [Side Effect];single drug dose;skin abrasion/si [Side Effect];skin discoloration/si [Side Effect];skin inflammation/si [Side Effect];skin irritation/si [Side Effect];stomach pain/si [Side Effect];urticaria/si [Side Effect];weight gain;Wilson disease/dt [Drug Therapy];2 [bis(2 pyridylmethyl)amino]propionate;8 quinolinol;antineoplastic agent;captopril/ae [Adverse Drug Reaction];captopril/cr [Drug Concentration];captopril/dt [Drug Therapy];captopril/po [Oral Drug Administration];casiopeina 3 1a [(1,1' dimethyl 2,2' bipiridine)(acetylacetonate) Copper (2) nitrate]/pd [Pharmacology];clioquinol/ae [Adverse Drug Reaction];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pk [Pharmacokinetics];copper/pd [Pharmacology];copper 3 hydroxy 5 hydroxymethyl 2 methyl 4 formylpyridine thiosemicarbazonato;copper 8 hydroxyquinoline 2 carboxaldehyde 4,4 dimethyl 3 thiosemicarbazide;copper n salicyloyl n' (2 furylthiocarbonyl) hydrazine;copper n' [(2 hydroxy phenyl) carbonothioyl] pyridine 2 carbohydrazide;copper thiophene 2 carbaldehyde thiosemicarbazone;copper tris (hydroxymethyl) phosphine;disulfiram;dithiocarbamic acid derivative/dt [Drug Therapy];fpa 37;hydrocortisone/ae [Adverse Drug Reaction];molybdenum/cr [Drug Concentration];molybdenum/pk [Pharmacokinetics];nci 109268;penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];penicillamine/iv [Intravenous Drug Administration];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];proteasome inhibitor/pd [Pharmacology];pyrrolidine dithiocarbamate;reactive oxygen metabolite/ec [Endogenous Compound];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/iv [Intravenous Drug Administration];tetrathiomolybdic acid/po [Oral Drug Administration];thiosemicarbazone/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cr [Drug Concentration];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics];trientine/pd [Pharmacology];trientine/sc [Subcutaneous Drug Administration];unclassified drug;zinc","Wang, F.;Jiao, P.;Qi, M.;Frezza, M.;Dou, Q. P.;Yan, B.",2010,,http://dx.doi.org/10.2174/092986710791859315,0,0,
1803,Zinc treatment in patients with symptomatic Wilson disease. [Spanish],,note;Wilson disease/dt [Drug Therapy];zinc/dt [Drug Therapy],"Bruguera, M.",2010,May-December,http://dx.doi.org/10.1016/S1578-1550%2810%2970062-0,0,0,
1804,Status dystonicus: A rare complication of dystonia,"A severe episode of dystonia refractory to standard drug therapy has been labeled as status dystonicus or dystonic storm. We report the development of this complication in a 10-year old boy with idiopathic torsion dystonia, the probable precipitating factor being either an infection or introduction of clonazepam.",Child;Dystonia;India;Management;Status dystonicus;abscess/dt [Drug Therapy];abscess/su [Surgery];article;case report;cerebral palsy/dt [Drug Therapy];chorea;conversion disorder/dt [Drug Therapy];drug dose increase;drug dose reduction;dysphagia;dystonic disorder/co [Complication];exhaustion;gait disorder;gluteus maximus muscle;human;hypersalivation;male;motor dysfunction;pain;school child;seizure/dt [Drug Therapy];sleep disorder;slurred speech;status dystonicus/co [Complication];torsion dystonia/dt [Drug Therapy];traditional medicine;Wilson disease;alpha tocopherol;alprazolam/dt [Drug Therapy];amoxicillin plus clavulanic acid/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];clonazepam/dt [Drug Therapy];diazepam/dt [Drug Therapy];levodopa/dt [Drug Therapy];multivitamin;penicillamine;tetrabenazine/dt [Drug Therapy];tizanidine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];valproic acid/dt [Drug Therapy];vitamin D;zinc,"Mishra, D.;Singhal, S.;Juneja, M.",2010,October,http://dx.doi.org/10.1007/s13312-010-0138-7,0,0,
1805,Hemolytic anemia as a presenting feature of wilson's disease: A case report,Wilson's disease is a rare inherited disorder of copper metabolism causing severe damage to vital organs. Liver and brain disorders are the main manifestations. Severe hemolytic anemia is an unusual complication of Wilson's disease. We present a case who developed spherocytic acute hemolytic anemia (Coomb's negative) as the initial manifestation of Wilson's disease. On examination Kayser- Fleischer ring was found. Laboratory data supported a diagnosis of Wilson's disease. © 2010 Indian Society of Haematology & Transfusion Medicine.,Spherocytic anemia;Wilson's disease (WD);abdominal distension;anamnesis;article;blood smear;case report;child;clinical feature;disease association;drug efficacy;erythrocyte disorder;erythrocyte transfusion;hemoglobin blood level;hemolytic anemia/dt [Drug Therapy];hemolytic anemia/di [Diagnosis];hemolytic anemia/th [Therapy];hepatomegaly;human;jaundice;liver function test;male;pallor;preschool child;reticulocyte count;spherocytic acute hemolytic anemia/di [Diagnosis];spherocytic acute hemolytic anemia/dt [Drug Therapy];spherocytic acute hemolytic anemia/th [Therapy];treatment duration;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Sharma, S.;Toppo, A.;Rath, B.;Harbhajanka, A.;Lalita Jyotsna, P.",2010,September,http://dx.doi.org/10.1007/s12288-010-0034-2,0,0,
1806,End stage liver failure,Advances in surgical techniques and immunosuppressive agents have led to paediatric liver transplantation being a standard treatment option for both acute and chronic liver failure with good long term outcome and quality of life. It is important to recognise the early clinical presentation and aetiology of hepatic disease so that accurate diagnosis and management may be initiated and referral to a specialist centre made. Children with liver disease should have shared care between a regional and specialist centre with timely referral for transplant assessment and further management when complications arise. © 2009 Elsevier Ltd. All rights reserved.,ascites;encephalopathy;liver failure;liver transplant;nutrition;portal hypertension;pruritis;sepsis;varices;Alagille syndrome/et [Etiology];alpha 1 antitrypsin deficiency;antibiotic prophylaxis;ascites/dt [Drug Therapy];autoimmune hepatitis/dt [Drug Therapy];bile duct atresia/su [Surgery];bleeding/dt [Drug Therapy];blood clotting disorder/dt [Drug Therapy];blood clotting disorder/pc [Prevention];blood clotting disorder/th [Therapy];brain disease/di [Diagnosis];brain disease/dt [Drug Therapy];brain edema;chelation therapy;cholangitis/dt [Drug Therapy];cholangitis/pc [Prevention];diagnostic accuracy;dietary intake;drug dose increase;electroencephalogram;erythrocyte concentrate;esophagus varices;fluid resuscitation;gene mutation;hepatopulmonary syndrome/su [Surgery];hepatorenal syndrome/dt [Drug Therapy];hepatorenal syndrome/su [Surgery];human;hypersplenism;intrahepatic cholestasis;liver cell carcinoma/co [Complication];liver failure/si [Side Effect];liver failure/co [Complication];liver failure/su [Surgery];liver fibrosis;liver transplantation;low drug dose;nonalcoholic fatty liver/su [Surgery];portoenterostomy;prognosis;pruritus/dt [Drug Therapy];quality of life;review;Roux Y anastomosis;sepsis/dt [Drug Therapy];thrombocyte transfusion;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alimemazine/dt [Drug Therapy];amoxicillin/dt [Drug Therapy];antibiotic agent/dt [Drug Therapy];antibiotic agent/po [Oral Drug Administration];azathioprine/dt [Drug Therapy];carbamazepine/ae [Adverse Drug Reaction];cefalexin/dt [Drug Therapy];cefotaxime/dt [Drug Therapy];colestyramine/dt [Drug Therapy];desmopressin/dt [Drug Therapy];fresh frozen plasma/dt [Drug Therapy];furosemide/dt [Drug Therapy];isoniazid/ae [Adverse Drug Reaction];naltrexone/dt [Drug Therapy];octreotide/dt [Drug Therapy];omeprazole/dt [Drug Therapy];omeprazole/iv [Intravenous Drug Administration];ondansetron/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];prednisolone/dt [Drug Therapy];ranitidine/dt [Drug Therapy];rifampicin/dt [Drug Therapy];spironolactone/dt [Drug Therapy];trimethoprim/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];valproic acid/ae [Adverse Drug Reaction];vancomycin/dt [Drug Therapy];vitamin K group/dt [Drug Therapy];vitamin K group/iv [Intravenous Drug Administration];vitamin K group/po [Oral Drug Administration];zinc/dt [Drug Therapy],"Hartley, J. L.;Kelly, D. A.",2010,January,http://dx.doi.org/10.1016/j.paed.2009.09.006,0,0,
1807,Drug induced myopathies. [Spanish],"Drug related myopathies are frequent. A history of use of medication is essential for its diagnosis. Without taking into account alcohol, drugs that frequently induce myopathies are steroids, colchicine, antimalarials, statins and cocaine. They can present muscle pain, proximal weakness and an increase in muscle enzymes. Suspension of the offending drug can lead to a cure in most of the cases. © 2010 Elsevier Espana, S.L.",Drug induced;Myophaty;Toxic myophathy;acne/dt [Drug Therapy];areflexia/si [Side Effect];article;Colchicum;convulsion/et [Etiology];creatinine urine level;Cushing syndrome/dt [Drug Therapy];cystinuria/dt [Drug Therapy];Danon disease/si [Side Effect];delirium/et [Etiology];drug dose reduction;drug induced disease/et [Etiology];drug induced myopathy/si [Side Effect];drug mechanism;drug megadose;drug metabolism;drug safety;drug withdrawal;electromyography;fibrinolysis;human;ischemic heart disease/dt [Drug Therapy];kidney failure/si [Side Effect];low drug dose;mitochondrial myopathy/et [Etiology];mitochondrial myopathy/si [Side Effect];muscle biopsy;muscle ischemia;muscle necrosis/et [Etiology];muscle necrosis/si [Side Effect];myalgia/si [Side Effect];myoglobinuria/et [Etiology];myopathy/si [Side Effect];myopathy/et [Etiology];myositis/et [Etiology];myositis/si [Side Effect];neuroleptic malignant syndrome/et [Etiology];neuropathy/si [Side Effect];pathogenesis;pathophysiology;polymyositis/dt [Drug Therapy];polymyositis/si [Side Effect];psoriasis/dt [Drug Therapy];rhabdomyolysis/si [Side Effect];rheumatoid arthritis/dt [Drug Therapy];systemic sclerosis/dt [Drug Therapy];toxic myopathy/si [Side Effect];treatment duration;vasoconstriction;Wilson disease/dt [Drug Therapy];alcohol/to [Drug Toxicity];alpha interferon/ae [Adverse Drug Reaction];alpha tocopherol/dt [Drug Therapy];alpha tocopherol/pd [Pharmacology];aminocaproic acid/ae [Adverse Drug Reaction];antimalarial agent/ae [Adverse Drug Reaction];chloroquine/ae [Adverse Drug Reaction];cholinesterase/ec [Endogenous Compound];cocaine/ae [Adverse Drug Reaction];cocaine/to [Drug Toxicity];colchicine/ae [Adverse Drug Reaction];creatine kinase/ec [Endogenous Compound];cyclosporin/ae [Adverse Drug Reaction];danazol/ae [Adverse Drug Reaction];dexamethasone;etretinate/dt [Drug Therapy];glucocorticoid/ae [Adverse Drug Reaction];glucocorticoid/do [Drug Dose];glucocorticoid/dt [Drug Therapy];glucocorticoid/ei [Epidural Drug Administration];glucocorticoid/ih [Inhalational Drug Administration];glucocorticoid/iv [Intravenous Drug Administration];glucocorticoid/po [Oral Drug Administration];hydroxychloroquine/ae [Adverse Drug Reaction];hydroxymethylglutaryl coenzyme A reductase inhibitor/ae [Adverse Drug Reaction];hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy];hydroxymethylglutaryl coenzyme A reductase inhibitor/pd [Pharmacology];isotretinoin/dt [Drug Therapy];ketoconazole/ae [Adverse Drug Reaction];labetalol/ae [Adverse Drug Reaction];nalidixic acid/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];procainamide/ae [Adverse Drug Reaction];rifampicin/ae [Adverse Drug Reaction];snake venom/to [Drug Toxicity];steroid/ae [Adverse Drug Reaction];triamcinolone;unindexed drug;vincristine/ae [Adverse Drug Reaction];zidovudine/ae [Adverse Drug Reaction],"Olive, A.",2010,September,http://dx.doi.org/10.1016/j.reuma.2010.05.002,0,0,
1808,Evaluation of the symptomatic treatment of residual neurological symptoms in Wilson disease,"The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detail. Copyright © 2010 S. Karger AG.",Movement disorder;Symptomatic treatment;Wilson disease;adult;article;dystonia/dt [Drug Therapy];female;human;major clinical study;male;neurologic disease;parkinsonism/dt [Drug Therapy];priority journal;questionnaire;symptomatology;tremor/dt [Drug Therapy];amantadine/dt [Drug Therapy];baclofen/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];biperiden/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];clonazepam/dt [Drug Therapy];levodopa/dt [Drug Therapy];metixene;penicillamine/cb [Drug Combination];primidone/dt [Drug Therapy];propranolol/dt [Drug Therapy];ropinirole/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];tiapride/dt [Drug Therapy];trientine/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];zinc/cb [Drug Combination],"Holscher, S.;Leinweber, B.;Hefter, H.;Reuner, U.;Gunther, P.;Weiss, K. H.;Oertel, W. H.;Moller, J. C.",2010,August,http://dx.doi.org/10.1159/000316066,0,0,
1809,The transition metals copper and iron in neurodegenerative diseases,"Neurodegenerative diseases constitute a worldwide health problem. Metals like iron and copper are essential for life, but they are also involved in several neurodegenerative mechanisms such as protein aggregation, free radical generation and oxidative stress. The role of Fe and Cu, their pathogenic mechanisms and possible therapeutic relevance are discussed regarding four of the most common neurodegenerative diseases, Alzheimer's, Parkinson's and Huntington's diseases as well as amyotrophic lateral sclerosis. Metal-mediated oxidation by Fenton chemistry is a common feature for all those disorders and takes part of a self-amplifying damaging mechanism, leading to neurodegeneration. The interaction between metals and proteins in the nervous system seems to be a crucial factor for the development or absence of neurodegeneration. The present review also deals with the therapeutic strategies tested, mainly using metal chelating drugs. Metal accumulation within the nervous system observed in those diseases could be the result of compensatory mechanisms to improve metal availability for physiological processes. © 2010 Elsevier Ireland Ltd.","Alzheimer's disease;Amyotrophic lateral sclerosis;Copper;Huntington's disease;Iron;Parkinson's disease;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/dt [Drug Therapy];amyotrophic lateral sclerosis/et [Etiology];antiinflammatory activity;antioxidant activity;bioaccumulation;clinical trial;cognitive defect/dt [Drug Therapy];copper metabolism;degenerative disease/et [Etiology];drug mechanism;drug penetration;Fenton reaction;Friedreich ataxia/dt [Drug Therapy];histopathology;human;Huntington chorea/dt [Drug Therapy];Huntington chorea/et [Etiology];iron metabolism;metal binding;neuropathology;neurotoxicity;nonhuman;oxidative stress;Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];pathophysiology;protein aggregation;protein interaction;review;senile plaque/dt [Drug Therapy];trace metal blood level;trinucleotide repeat;Wilson disease/dt [Drug Therapy];2 methyl 5 (3,4,5 trimethoxybenzamido)decahydroisoquinoline/pd [Pharmacology];beta lactam antibiotic/dt [Drug Therapy];chelating agent/dt [Drug Therapy];clioquinol/dt [Drug Therapy];clioquinol/pk [Pharmacokinetics];clioquinol/pd [Pharmacology];copper/ec [Endogenous Compound];copper chelating agent/dt [Drug Therapy];copper complex/dt [Drug Therapy];copper complex/pd [Pharmacology];curcumin/dt [Drug Therapy];curcumin/pd [Pharmacology];deferiprone/dt [Drug Therapy];deferiprone/pk [Pharmacokinetics];deferiprone/pd [Pharmacology];deferoxamine/ct [Clinical Trial];deferoxamine/dt [Drug Therapy];diethyldithiocarbamic acid/dt [Drug Therapy];diethyldithiocarbamic acid/pd [Pharmacology];epigallocatechin gallate/dt [Drug Therapy];epigallocatechin gallate/pd [Pharmacology];free radical/ec [Endogenous Compound];Ginkgo biloba extract/dt [Drug Therapy];Ginkgo biloba extract/pd [Pharmacology];glyoxalbis(n4 methyl 3 thiosemicarbazonato)copper complex/dt [Drug Therapy];glyoxalbis(n4 methyl 3 thiosemicarbazonato)copper complex/pd [Pharmacology];hla 20/pd [Pharmacology];iron/ec [Endogenous Compound];iron chelating agent/pd [Pharmacology];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];placebo;pyrrolidine dithiocarbamate/pd [Pharmacology];salicylaldehyde isonicotinoyl hydrazone/dt [Drug Therapy];salicylaldehyde isonicotinoyl hydrazone/pd [Pharmacology];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/pd [Pharmacology];transition element/ec [Endogenous Compound];unclassified drug;vk 28/pd [Pharmacology]","Rivera-Mancia, S.;Perez-Neri, I.;Rios, C.;Tristan-Lopez, L.;Rivera-Espinosa, L.;Montes, S.",2010,July,http://dx.doi.org/10.1016/j.cbi.2010.04.010,0,0,
1810,"Predominant ataxia, low ceruloplasmin, and absent K-F rings: Hypoceruloplasminemia or wilson's disease",,acanthocytosis;adult;ataxia;autosomal recessive disorder;blood cell count;blood level;bradykinesia;brain atrophy;case report;cervical dystonia;clinical examination;cognitive defect;concentration (parameters);differential diagnosis;drug substitution;drug withdrawal;dysarthria;dysmetria;dystonia;female;follow up;gait disorder;gene mutation;genetic variability;globus pallidus;human;hypoceruloplasminemia/di [Diagnosis];hypoceruloplasminemia/dt [Drug Therapy];inborn error of metabolism;iris;kayser fleischer ring;letter;liver biopsy;liver cell;metabolic disorder/dt [Drug Therapy];metabolic disorder/di [Diagnosis];nuclear magnetic resonance imaging;peripheral blood mononuclear cell;priority journal;psychomotor disorder;putamen;screening;slit lamp;slurred speech;spinocerebellar degeneration;thumb;treatment response;tremor;unspecified side effect/si [Side Effect];urine level;Wilson disease/di [Diagnosis];alpha tocopherol;ceruloplasmin/ec [Endogenous Compound];copper;desferroxamine/ae [Adverse Drug Reaction];desferroxamine/dt [Drug Therapy];ferritin;gliadin antibody;heavy metal;iron;iron chelating agent/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug,"Mehta, S. H.;Parekh, S. M.;Prakash, R.;Morgan, J. C.;Miyajima, H.;Sethi, K. D.",2010,15 Oct,http://dx.doi.org/10.1002/mds.23000,0,0,
1811,Investigational approaches to therapies for idiopathic pulmonary fibrosis,"Importance of the field: In fibrosing diseases, scar tissue begins to replace normal tissue, causing tissue dysfunction. For instance, in lung fibrosis, foci of what resembles scar tissue form in the lungs, impeding the ability of patients to breathe. These conditions represent a significant source of morbidity and mortality. More than 150,000 people in the USA have some form of fibrotic lung disease, and the 5-year mortality rate for these diseases can be as high as 80%. Despite this large unmet medical need, there are no FDA-approved therapies. Although our understanding of the causes and the biology of fibrosing diseases remains relatively poor, we have made impressive advances in identifying the major cell populations and many biochemical mediators that can drive this process. As a result, novel therapeutics are being developed based upon these discoveries. Areas covered in this review: This review examines the experimental therapies currently under investigation as of late 2009 for a major class of lung fibrosis called idiopathic pulmonary fibrosis (IPF). What the reader will gain: The reader will gain an overview of current experimental therapies for IPF. Take home message: With the recent approval of Pirfenidone in Japan for use in IPF, and a rich pipeline of experimental therapies in various stages of clinical development, the future looks bright for new treatment options. © 2010 Informa UK Ltd.",Epithelialmesenchymal transition;Fibroblast;Fibrocyte;Fibrosis;Idiopathic pulmonary fibrosis;Lung;allergic asthma;asthma/dt [Drug Therapy];chronic myeloid leukemia/dt [Drug Therapy];clinical trial;coughing/dt [Drug Therapy];coughing/pc [Prevention];dosage schedule comparison;drug dose comparison;drug dose escalation;drug dose increase;erectile dysfunction/dt [Drug Therapy];exercise tolerance;fibrosing alveolitis/dt [Drug Therapy];forced vital capacity;human;interstitial lung disease/dt [Drug Therapy];kidney fibrosis/dt [Drug Therapy];liver fibrosis/dt [Drug Therapy];lung diffusion capacity;lung fibrosis/dt [Drug Therapy];lung fibrosis/pc [Prevention];mortality;multiple myeloma/dt [Drug Therapy];neoplasm/dt [Drug Therapy];nonhuman;prevalence;progression free survival;pulmonary hypertension/dt [Drug Therapy];review;scleroderma/dt [Drug Therapy];systemic sclerosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];acetylcysteine/ct [Clinical Trial];acetylcysteine/cb [Drug Combination];acetylcysteine/dt [Drug Therapy];acetylcysteine/po [Oral Drug Administration];azathioprine/ct [Clinical Trial];azathioprine/cb [Drug Combination];azathioprine/cm [Drug Comparison];azathioprine/dt [Drug Therapy];bibf 1120/ct [Clinical Trial];bibf 1120/dt [Drug Therapy];bibf 1120/po [Oral Drug Administration];bosentan/ct [Clinical Trial];bosentan/dt [Drug Therapy];cnto 888/ct [Clinical Trial];cnto 888/dt [Drug Therapy];cnto 888/iv [Intravenous Drug Administration];coprexa;etanercept/ct [Clinical Trial];etanercept/dt [Drug Therapy];etanercept/sc [Subcutaneous Drug Administration];fg 3019/ct [Clinical Trial];fg 3019/dt [Drug Therapy];fg 3019/iv [Intravenous Drug Administration];gc 1008/ct [Clinical Trial];gc 1008/dt [Drug Therapy];gc 1008/iv [Intravenous Drug Administration];imatinib/ct [Clinical Trial];imatinib/dt [Drug Therapy];imatinib/po [Oral Drug Administration];minocycline/ct [Clinical Trial];minocycline/dt [Drug Therapy];minocycline/po [Oral Drug Administration];monoclonal antibody/ct [Clinical Trial];monoclonal antibody/dt [Drug Therapy];monoclonal antibody/iv [Intravenous Drug Administration];octreotide/ct [Clinical Trial];octreotide/dt [Drug Therapy];octreotide/im [Intramuscular Drug Administration];pirfenidone/ct [Clinical Trial];pirfenidone/dt [Drug Therapy];pirfenidone/po [Oral Drug Administration];placebo;prednisone/ct [Clinical Trial];prednisone/cb [Drug Combination];prednisone/cm [Drug Comparison];prednisone/dt [Drug Therapy];prm 151/ct [Clinical Trial];prm 151/dt [Drug Therapy];prm 151/iv [Intravenous Drug Administration];serum amyloid P/ct [Clinical Trial];serum amyloid P/dt [Drug Therapy];serum amyloid P/iv [Intravenous Drug Administration];sildenafil/ct [Clinical Trial];sildenafil/dt [Drug Therapy];sildenafil/po [Oral Drug Administration];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration];thalidomide/ct [Clinical Trial];thalidomide/dt [Drug Therapy];thalidomide/po [Oral Drug Administration];unclassified drug;zileuton/ct [Clinical Trial];zileuton/cm [Drug Comparison];zileuton/dt [Drug Therapy];zileuton/po [Oral Drug Administration],"Gomer, R. H.;Lupher Jr, M. L.",2010,June,http://dx.doi.org/10.1517/13543784.2010.484018,0,0,
1812,Influence of copper on early development: Prenatal and postnatal considerations,"Copper (Cu) is an essential nutrient whose requirement is increased during pregnancy and lactation. These represent times of critical growth and development, and the fetus and neonate are particularly vulnerable to deficiencies of this nutrient. Genetic mutations that predispose the offspring to inadequate stores of Cu can be life threatening as is observed in children with Menkes disease. During the last decade, severe Cu deficiency, once thought to be a rare condition, has been reported in the literature at an increasing frequency. Secondary Cu deficiencies can be induced by a variety of ways such as excessive zinc or iron intake, certain drugs, and bariatric surgery. Premature and low birth weight infants can be born with low Cu stores. A number of mechanisms can contribute to the teratogenicity of Cu including decreased activity of select cuproenzymes, increased oxidative stress, decreased nitric oxide availability, altered iron metabolism, abnormal extracellular matrix protein crosslinking, decreased angiogenesis and altered cell signaling among others. The brain, heart, and vessels as well as tissues such as lung, skin and hair, and systems including the skeletal, immune, and blood systems, are negatively affected by suboptimal Cu during development. Additionally, persistent structural, biochemical, and functional adverse effects in the offspring are noted even when Cu supplementation is initiated after birth, supporting the concept that adequate Cu nutriture during pregnancy and lactation is critical for normal development. Although Cu-containing IUDs are an effective method for increasing intrauterine Cu concentrations and for reducing the risk of pregnancy, high amounts of dietary Cu are not thought to represent a direct developmental risk. © 2010 International Union of Biochemistry and Molecular Biology, Inc.",Copper deficiency;Embryo;Nitric oxide;Pregnancy;anemia/et [Etiology];anemia/si [Side Effect];angiogenesis;apoptosis;arthrogryposis/si [Side Effect];behavior;bone disease;brain;cardiomyopathy/et [Etiology];central nervous system disease/et [Etiology];clinical assessment;clinical feature;copper blood level;copper deficiency/si [Side Effect];copper deficiency/di [Diagnosis];copper deficiency/et [Etiology];copper metabolism;corpus callosum agenesis/si [Side Effect];cutis laxa/si [Side Effect];diet supplementation;dietary intake;embryo development;enzyme activity;extracellular matrix;gene mutation;hair disease/si [Side Effect];heart development;human;hypertrophic cardiomyopathy/et [Etiology];hypothyroidism/si [Side Effect];inguinal hernia/si [Side Effect];intrauterine contraceptive device;iron metabolism;lactation;maternal nutrition;Menkes syndrome/et [Etiology];micrognathia/si [Side Effect];motor dysfunction/et [Etiology];nerve cell necrosis;neurologic disease/et [Etiology];neutropenia/et [Etiology];neutropenia/si [Side Effect];nitrosative stress;nonhuman;oxidative stress;postnatal development;prematurity/et [Etiology];prenatal development;priority journal;progeny;protein expression;protein function;protein phosphorylation;review;risk factor;side effect/si [Side Effect];signal transduction;teratogenicity/et [Etiology];vascularization;very low birth weight/et [Etiology];weight gain;Wilson disease;yolk sac;binding protein/ec [Endogenous Compound];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper binding protein/ec [Endogenous Compound];copper transporter 1/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];cytochrome c/ec [Endogenous Compound];dithiocarbamic acid/to [Drug Toxicity];endothelial nitric oxide synthase/ec [Endogenous Compound];iron;membrane protein/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];nitric oxide/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/to [Drug Toxicity];peroxisome proliferator activated receptor gamma coactivator 1alpha/ec [Endogenous Compound];protein lysine 6 oxidase/ec [Endogenous Compound];scleroprotein/ec [Endogenous Compound];sonic hedgehog protein/ec [Endogenous Compound];unclassified drug;vasculotropin/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction],"Uriu-Adams, J. Y.;Scherr, R. E.;Lanoue, L.;Keen, C. L.",2010,,http://dx.doi.org/10.1002/biof.85,0,0,
1813,Lead poisoning: Basics and new developments,"* Based on strong research evidence, no measurable BLL is considered safe. * Because neurotoxicity associated with lower BLLs has been established by overwhelmingly consistent evidence from meta-analysis of several cohort studies, primary prevention of lead exposure is of paramount importance. * Lead exerts its effects on multiple body systems (some evidence), with the developing brain being particularly vulnerable (strong evidence). * No current evidence shows that pharmacotherapy in patients who have high BLLs reverses lead neurotoxicity. Targeted at-risk screening and early intervention for elevated BLLs, as currently recommended by the CDC and the American Academy of Pediatrics, should be conducted by every primary care practitioner to minimize the deleterious effects of lead in children.",abdominal cramp/si [Side Effect];air;continuous infusion;diet therapy;drug eruption/si [Side Effect];drug induced headache/si [Side Effect];environmental factor;hemolysis/si [Side Effect];human;hyperpyrexia/si [Side Effect];hypertension/si [Side Effect];hypokalemia/si [Side Effect];kidney disease/si [Side Effect];lead poisoning/dt [Drug Therapy];lead poisoning/ep [Epidemiology];leukopenia/si [Side Effect];nausea/si [Side Effect];neurotoxicity;neutropenia/si [Side Effect];occupational exposure;public health service;review;side effect/si [Side Effect];single drug dose;tachycardia/si [Side Effect];thrombocytopenia/si [Side Effect];vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];zinc deficiency/si [Side Effect];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/cb [Drug Combination];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];edetate calcium disodium/ae [Adverse Drug Reaction];edetate calcium disodium/cb [Drug Combination];edetate calcium disodium/cm [Drug Comparison];edetate calcium disodium/dt [Drug Therapy];edetate calcium disodium/im [Intramuscular Drug Administration];edetate calcium disodium/iv [Intravenous Drug Administration];paint;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];succimer/ae [Adverse Drug Reaction];succimer/cm [Drug Comparison];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];water,"Chandran, L.;Cataldo, R.",2010,October,http://dx.doi.org/10.1542/pir.31-10-399,0,0,
1814,Mutations of ATP7B gene in two Thai siblings with Wilson disease,"Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B gene. Objective: Report the clinical data and mutation analysis of two Thai siblings suspected of WD. Subject and methods: A 13-year-old boy who presented with cirrhosis, arthralgia, hypoalbuminemia, and coagulopathy, and his 11-year-old sister who was asymptomatic but had hepatomegaly with elevation of transaminases, were studied. Mutation analysis of ATP7B gene and mRNA analysis was performed in both patients and their parents. Results: Investigations were consistent with WD, and their liver diseases improved after standard treatment for WD. DNA analyses in these two patients revealed two novel mutations, which were a deletion of the first 2bp of exon 6 (c.1870-1871delGA), and a single base substitution from A to G at nucleotide 4075 (c.4075A>G) in the exon 20 (p.M1359V). PCR-restriction digestion with NcoI restriction enzyme was employed as the second method for confirmation of the c.4075A>G mutation and for rapid screening in 100 chromosomes from unrelated healthy controls, and this variant was not present in the controls. The c.1870-1871delGA deletion caused a frameshift effect, which results in a premature stop codon (p.E624fsX753), and the p.M1359V mutation is a substitution of methionine with valine, which may have effects upon its orientation and interaction with other adjacent amino acids. Conclusion: Two novel mutations of ATP7B gene were identified in two Thai siblings with WD.",ATP7B gene;Cirrhosis;Liver disease;Wilson disease;abdomen;adolescent;arthralgia;article;blood clotting disorder;case report;ceruloplasmin blood level;child;codon;echography;exon;female;frameshift mutation;gene deletion;genetic variability;human;hypoalbuminemia;liver cirrhosis;male;mutational analysis;nucleotide sequence;parent;polymerase chain reaction;school child;sibling;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];DNA/ec [Endogenous Compound];messenger RNA/ec [Endogenous Compound];methionine/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];valine/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Treepongkaruna, S.;Pienvichit, P.;Phuapradit, P.;Kodcharin, P.;Wattanasirichaigoon, D.",2010,February,,0,0,
1815,Atypical linear toxicodermia by sorafenib,,adult;artificial embolism;case report;chemotherapy induced emesis/si [Side Effect];diarrhea/si [Side Effect];drug withdrawal;eyelid edema/si [Side Effect];female;gastrointestinal symptom/si [Side Effect];histopathology;human;human tissue;letter;liver cell carcinoma/dt [Drug Therapy];nausea/si [Side Effect];physical examination;skin biopsy;skin toxicity/si [Side Effect];toxicoderma/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];sorafenib/ae [Adverse Drug Reaction];sorafenib/dt [Drug Therapy],"Rodriguez-Vazquez, M.;Martinez-Martinez, M. L.;Garcia-Arpa, M.;de Onzono, L. I.",2010,October,http://dx.doi.org/10.1111/j.1365-4632.2010.04518.x,0,0,
1816,Wilson's disease,"Wilson's disease is an autosomal-recessive disorder caused by mutation in the ATP7B gene. Absent or reduced function of ATP7B protein leads to decreased hepatocellular excretion of copper into bile. Subsequent copper accumulation, first in the liver but ultimately in the brain and other tissues, produces different clinical manifestations such as hepatic, neurological, hematological, ophthalmological, and psychiatric problems. Diagnosis is based on clinical suspicion, parameters of copper metabolism, ophthalmic examination (Kayser-Fleischer rings) and a liver biopsy. Genetic studies are of limited use. Early diagnosis and initiation of therapy with chelators and therapeutic plasma exchange therapy are essential for prognosis. Liver transplantation corrects the underlying pathophysiology and can be lifesaving in fulminant hepatic failure. Screening of siblings and 1st degree relatives of the patients is also important. © 2010 Versita Warsaw and Springer-Verlag Berlin Heidelberg.",Chelating agents;Copper metabolism;Kayser-Fleischer rings;Liver transplantation;Wilson's disease;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/et [Etiology];bile;biochemistry;bone marrow suppression/si [Side Effect];clinical feature;copper blood level;diagnostic procedure;drug efficacy;early diagnosis;eye disease;eye examination;gene mutation;genetic analysis;hematologic disease;human;kidney disease/si [Side Effect];liver biopsy;liver disease;liver failure;liver function test;lupus like syndrome/si [Side Effect];mental disease;neurologic disease;pathophysiology;plasmapheresis;priority journal;prognosis;protein function;review;screening;skin disease/si [Side Effect];unspecified side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alpha tocopherol/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Hursitoglu, M.;Cikrikcioglu, M. A.;Danalioglu, A.;Tukek, T.",2010,April,http://dx.doi.org/10.2478/s11536-010-0004-y,0,0,
1817,Wilson disease evaluation of disease-related topics through the eyes of patients by patient-generated paintings A cooperative study with the German patient organisation verein morbus wilson e. V. [German],"Background: The importance of disease-related topics can vary widely between patients and doctors. Patient organisations such as the German Verein Morbus Wilson e. V. can overcome this discrepancy. The goal of the present cooperative study was the collection of topics important to Wilson patients by asking patients to generate paintings about their disease. Methods: Patients with Wilson disease were asked by mail to draw paintings about their disease and to donate them to the Verein Morbus Wilson e. V. Results: 32 paintings from 27 patients were donated. The majority of the patients added written comments to their art work. Disease-related topics included in the paintings were as follows: psychological work-up of the disease 33 % (n = 11), presentation of affeced organs (liver/brain) 22 % (n = 6), therapy 19 % (n = 5), diagnostic path 15 % (n = 4), inheritance 15 % (n = 4), copper-related diet 11 % (n = 3). 33 % (n = 11) of the paintings were composed of two parts reflecting before and after the disease or presenting the individual time course of the disease. Conclusion: Psychological aspects of disease acceptance are the prominent topic in the paintings. The timepoint of diagnosis is experienced as major change in life. The paintings enable both the patient organisation and the caretakers to put more focus on the psychological aspects of the disease. Asking for paintings opens a new channel for patient-physican contacts and produces a feeling of interest and competence in patients.",copper;liver;metabolic disease;Wilson disease;article;clinical article;depression;fatigue;hopelessness;hospitalization;human;inheritance;painting;pathophysiology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];trientine/dt [Drug Therapy],"Schafer, M.;Weiss, K. H.;Merle, U.;Stremmel, W.;Rasp, B.",2010,,http://dx.doi.org/10.1055/s-0029-1245305,0,0,
1818,Zinc bells rang in Jerusalem!,"""Oh, Jerusalem of gold, and of light, and of bronze..."" goes the popular song. But it was another metal that towered above the Jerusalem landscape during the meeting of the International Society for Zinc Biology (ISZB; http://www.iszb.org/), held at Mishkenot Sha'ananim, a whisper away from the Old City walls. More than 100 scientists gathered on 1 to 5 December 2009 to discuss their research on the biology of this metal. Zinc is a double-edged sword. Zinc supplementation accelerates wound healing and growth and promotes an effective immune response. On the other hand, zinc deficiency leads to growth retardation and impaired learning and memory function, and has been linked to mood disorders. At the cellular level, however, uncontrolled increases in zinc concentrations can lead to neuronal cell death and may be involved in neurodegenerative disorders. Through regulation of various intracellular signaling pathways, zinc can accelerate cell growth and possibly contribute to cancer. However, despite the physiological and clinical importance of this metal, research on the molecular basis of these effects is still in its infancy. The 2009 ISZB meeting provided a venue for investigators working on various zinc-related issues to share their thoughts and ideas and to promote the growth of this field. Copyright 2008 by the American Association for the Advancement of Science; all rights reserved.",adjuvant therapy;Alzheimer disease/et [Etiology];anhedonia;anorexia;anxiety disorder;cancer cell;cell cycle;cellular distribution;conference paper;degenerative disease/et [Etiology];depression/dt [Drug Therapy];diet supplementation;fluorescence microscopy;gene mutation;growth retardation;hippocampus;homeostasis;human;immune response;Israel;learning disorder;long term potentiation;mammary gland;memory disorder;mental disease/et [Etiology];mood disorder/et [Etiology];nerve cell necrosis;nervous system;neurologic disease/et [Etiology];nonhuman;organization;oxidative stress;priority journal;secretory vesicle;signal transduction;Wilson disease;wound healing;zinc deficiency/dt [Drug Therapy];zinc deficiency/pc [Prevention];amyloid beta protein/ec [Endogenous Compound];antidepressant agent/dt [Drug Therapy];binding protein/ec [Endogenous Compound];brain derived neurotrophic factor/ec [Endogenous Compound];calcium calmodulin dependent protein kinase/ec [Endogenous Compound];mitogen activated protein kinase;n methyl dextro aspartic acid receptor/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc transporter/ec [Endogenous Compound],"Hershfinkel, M.;Aizenman, E.;Andrews, G.;Sekler, I.",2010,06 Jul,http://dx.doi.org/10.1126/scisignal.3129mr2,0,0,
1819,Can tetrathiomolybdate be a potential agent against Alzheimer disease? A hypothesis based on abnormal copper homeostasis in brain,,Alzheimer disease/et [Etiology];Alzheimer disease/pc [Prevention];amyotrophic lateral sclerosis/dt [Drug Therapy];animal experiment;animal model;blood brain barrier;brain;central nervous system;copper deficiency;copper metabolism;degenerative disease;drug penetration;enzyme activity;homeostasis;human;Huntington chorea/dt [Drug Therapy];letter;mouse;multiple sclerosis/dt [Drug Therapy];neurologic disease;nonhuman;priority journal;Wilson disease/dt [Drug Therapy];copper;copper zinc superoxide dismutase/ec [Endogenous Compound];immunoglobulin enhancer binding protein/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology],"Farshchi, S.;Zamiri, N.;Sabayan, B.",2010,July-September,http://dx.doi.org/10.1097/WAD.0b013e3181d5e5a3,0,0,
1820,Wilson's disease: A review. [Spanish],"Wilson's disease is an autosomal recessive disorder caused by mutations in the ATP7B gene that lead to an abnormal metabolism of copper, resulting in the accumulation of this element in several organs and tissues. Its diagnosis is based on the combination of the clinical picture with various biochemical tests, neither one of which is, by itself, diagnostic of the disease. Presently there are effective treatments for EW based on the administration of chelating agents to promote mobilization of copper from the accumulation sites and its excretion. Zinc is also used in order to block the intestinal absorption of copper. Liver transplantation is the treatment of choice in patients with fulminating hepatitis, as well as in those with decompensated cirrhosis. This review includes the following aspects of Wilson's disease: biochemical, genetic, clinical, diagnostic, and therapeutic.",Chelating agents;Copper metabolism;Hepatolenticular degeneration;Wilson's disease;clinical feature;eye disease;gene mutation;human;liver metabolism;liver transplantation;mental disease;neurologic disease;prognosis;review;Wilson disease/di [Diagnosis];Wilson disease/su [Surgery],"Herrera, Y. P. E.;Ruiz, L. M. M.;Gutierrez, J. C. R.",2010,March,,0,0,
1821,Resected multiple hepatocellular carcinoma associated with Wilson's disease presenting with neurological complication: Report of a case. [Japanese],"A 54-year-old female with Wilson's disease had been treated with D-penicillamine for 24 years. A hypervascular hepatic tumor was found in S6 and it was diagnosed as a hemangioma at that time. Seventeen months later, the hepatic tumor number and size increased. There were more than 4 tumors and the maximum size of the tumor was over 5 cm. The liver function was evaluated as Child-Pugh Grade A. These tumors were diagnosed as multiple HCC and transcatheter arterial chemoembolization was performed. Six weeks later, CT showed viable lesions and all tumors existed in S5-6. The neurological symptoms were stable, and therefore all of the tumors were removed by a hepatic resection (S5-6). A pathological examination showed liver cirrhosis and all tumors were moderately differentiated HCC. No copper deposition was observed with rhodamine stain. The post-operative course was good and both the liver function and neurological signs have since remained stable. No tumor has appeared during the 14 months post-operative period. © 2010 The Japan Society of Hepatology.",Hepatic resection;Hepatocellular carcinoma;Neurological symptoms;Wilson's disease;adolescent;adult;article;chemoembolization;clinical article;disease association;disease course;female;hemangioma;human;liver cell carcinoma/su [Surgery];liver function;liver resection;male;neurologic disease/co [Complication];treatment outcome;Wilson disease/dt [Drug Therapy];fluorouracil;penicillamine/dt [Drug Therapy],"Ikubo, A.;Hotta, K.;Sakai, M.;Yamaji, K.;Mitsuno, M.;Samejima, R.;Tabuchi, M.;Yunotani, S.;Handa, M.;Yamasaki, F.",2010,,http://dx.doi.org/10.2957/kanzo.51.379,0,0,
1822,"Clinical features of hemolysis, elevated liver enzymes, and low platelet count syndrome in undiagnosed Wilson disease: Report of two cases","Introduction: Wilson's disease (WD) is an autosomal recessive disorder characterized by toxic accumulation of copper mainly in the liver and brain. The hepatic manifestation of WD is diverse and may include asymptomatic elevation of aminotransferase, chronic hepatitis, cirrhosis, or acute/fulminant hepatic failure. Characteristic of acute hepatic failure in WD is concomitance of acute intravascular hemolytic anemia that in some patients may represent a first clinical symptom of WD. The diagnosis of acute Wilsonian liver failure is difficult, as similar signs may be observed in other clinical conditions. In pregnant patients with unrecognized WD, liver failure with hemolysis may be interpreted as the low platelet count (HELLP) syndrome. Patients: We describe two women, who developed the clinical features of hemolysis, elevated liver enzymes, and HELLP syndrome. In both, further diagnostics confirmed WD. Conclusion: WD should be remembered in the differential diagnostics of HELLP syndrome. © 2009 Springer-Verlag.",HELLP syndrome;Pregnancy;Wilson's disease;adult;article;ataxia;blood pressure;blood transfusion;brain hematoma/su [Surgery];case report;ceruloplasmin blood level;cesarean section;computer assisted tomography;consciousness level;diagnostic value;differential diagnosis;erythrocyte count;female;gene mutation;genetic analysis;hand tremor;HELLP syndrome/di [Diagnosis];HELLP syndrome/dt [Drug Therapy];hematocrit;human;intensive care unit;international normalized ratio;leukocyte count;leukocytosis;mean corpuscular volume;plasma transfusion;preeclampsia;seizure;slurred speech;thrombocyte count;thrombocytopenia;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartic acid/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];blood clotting factor 7a/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];penicillamine;protein/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy],"Czlonkowska, A.;Gromadzka, G.;Buttner, J.;Chabik, G.",2010,January,http://dx.doi.org/10.1007/s00404-009-1080-6,0,0,
1823,Unexpected combination of inherited chorea-acanthocytosis with MDR3 (ABCB4) defect mimicking Wilson's disease,,adult;alanine aminotransferase blood level;ascites;case report;chorea-acanthocytosis/di [Diagnosis];chorea-acanthocytosis/dt [Drug Therapy];chorea-acanthocytosis/su [Surgery];chromosome 7;family history;gallbladder disease/di [Diagnosis];gallbladder lithiasis/di [Diagnosis];gamma glutamyl transferase blood level;grand mal epilepsy;human;inheritance;jaundice;letter;liver biopsy;liver cirrhosis/di [Diagnosis];liver transplantation;male;missense mutation;multidrug resistance protein 3 deficiency/di [Diagnosis];polyneuropathy/di [Diagnosis];priority journal;protein deficiency/di [Diagnosis];splenomegaly/di [Diagnosis];thrombocyte count;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];copper;creatine kinase/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];multidrug resistance protein 3/ec [Endogenous Compound];multidrug resistance protein 4/ec [Endogenous Compound];phenobarbital/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Anheim, M.;Chamouard, P.;Rudolf, G.;Ellero, B.;Vercueil, L.;Goichot, B.;Marescaux, C.;Tranchant, C.",2010,September,http://dx.doi.org/10.1111/j.1399-0004.2010.01386.x,0,0,
1824,"Wilson's disease: Clinical, brain MRI and Tc-99m HMPAO SPECT correlation","Background: Brain damage secondary to Wilson's disease leads to several psychiatric and neurological manifestations. However, little research has been published about the role of anatomo-functional diagnostic modalities in the evaluation of the disease course. Objective: To evaluate and compare the role of brain MRI and Tc-99m HMPAO SPECT in assessing brain involvement in Wilson's disease and correlating these findings with the clinical presentations. Methods: Eighteen patients with established Wilson's disease were included. The clinical picture was of neurologic type (nWD) in 11 patients (61.1%), and of the hepatic type (hWD) in 7 patients (38.9%). All patients were subjected to clinical assessment, cognitive assessment, ophthalmic slit lamp examination, biochemical tests including urinary copper and serum ceruloplasmin levels, abdominal ultrasound, liver biopsy (only in 5 patients), MRI of the brain and Tc-99m HMPAO brain SPECT. Results: Brain MRI was abnormal in 11/18 patients (sensitivity 61.1%). It was abnormal in 9/11 nWD patients (sensitivity 81.8%) and 2/7 of hWD patients (sensitivity 28.6%). Brain Tc-99m HMPAO SPECT was abnormal in 15 out of 18 patients (sensitivity 83.3%). The scan was abnormal in 10/11 patients with nWD (sensitivity 90.9%) and in 5/7 of patients with hWD (sensitivity 71.4 %). There was a good correlation between the clinical presentation of the disease and radiological and SPECT findings. Conclusion: In Wilson's disease brain SPECT has a higher sensitivity than brain MRI in detecting brain damage. There was also a good clinico-anatomical correlation but it was still not clear yet in explaining some clinical aspects in some cases.",Brain MRI;Brain SPECT;Wilson's disease;adult;article;behavior change;brain atrophy/di [Diagnosis];brain damage/di [Diagnosis];ceruloplasmin blood level;chorea;clinical article;clinical assessment;clinical feature;controlled study;dysarthria;dystonia;echography;eye examination;female;human;human tissue;hypersalivation;intermethod comparison;jaundice;liver biopsy;male;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;seizure;sensitivity analysis;single photon emission computer tomography;slit lamp;tremor;unsteadiness;urinalysis;vomiting;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hexamethylpropylene amine oxime technetium tc 99m;penicillamine/dt [Drug Therapy],"El-Sayed, M. A.;Salem, S.;Taha, A. E. H.;Kassem, A. E. M.",2010,January,,0,0,
1825,Sleep in Wilson's disease: A polysomnography-based study,"Wilson's disease (WD) has neuro-anatomical, pathophysiological and neurochemical basis for sleep disturbances. The aim of the study was objective evaluation of the frequency and nature of sleep abnormalities using polysomnography (PSG) in patients with WD. The study included 25 subjects with WD (males, 18; age , 24.4 +/- 9.25 years) and 25 healthy controls (all males; age, 33.1 +/- 9.7 years). After phenotypic assessment and magnetic resonance imaging (MRI), sleep-related questionnaires were administered, and PSG was performed. Patients had significantly reduced total sleep-time (P=.001), sleep-efficiency (P=.001), percentage of deep sleep (P=.01), and REM-sleep (P=.04) with prolonged sleep-onset latency (P=.05) and latency to stage 2 (P=.02). Subgroup analyses of patients based on demographic and clinical parameters were done. Men had significantly more bradycardia both during awake (P=.002) and sleep (P=.03) states. Younger patients (<20 years) had frequent tachycardia (P=.01), higher Periodic Limb Movement (PLM) Index (P=.01) and lesser REM% sleep (P=.05). Patients on de-coppering therapy had prolonged REM-sleep-onset latency (P=.03) and mixed apnea events (P=.04). The isolated limb movements were more in the severe form of disease (P=.05) and in patients taking anticonvulsants (P=.03). This study, the first of its kind in literature, revealed significant sleep disturbances in patients with Wilson's disease.",Polysomnography;sleep;Wilson's disease;adult;age distribution;apnea;article;bradycardia;clinical article;clinical feature;controlled study;disease severity;female;human;limb movement;male;morning dosage;nonREM sleep;nuclear magnetic resonance imaging;periodic limb movement index;phenotype;questionnaire;rating scale;REM sleep;seizure/dt [Drug Therapy];sleep disorder;sleep stage;sleep time;tachycardia;wakefulness;Wilson disease/dt [Drug Therapy];carbamazepine/cb [Drug Combination];carbamazepine/dt [Drug Therapy];clonazepam;penicillamine/dt [Drug Therapy];phenobarbital/cb [Drug Combination];phenobarbital/dt [Drug Therapy];phenytoin/cb [Drug Combination];phenytoin/dt [Drug Therapy];propranolol;trihexyphenidyl;zinc sulfate/dt [Drug Therapy],"Netto, A. B.;Sinha, S.;Taly, A. B.;Panda, S.;Rao, S.",2010,November-December,http://dx.doi.org/10.4103/0028-3886.73752,0,0,
1826,An unusual manifestation of Wilson disease presenting with burning feet syndrome,"Background: Wilson disease is rarely associated with peripheral neuropathy. Case Report: We report on a 50 y old male with an unusual manifestation of Wilson disease. The patient presented with burning feet syndrome. Nerve conduction studies revealed a mild axonal and myelin damage. In genetic testing, a homozygous point mutation (c.3207C>A) on the ATP7B gene was found. Conclusions: Physicians should be aware that patients suffering from Wilson disease may present with a broad spectre of symptoms, including signs of polyneuropathy. © Internet Scientific Publications, LLC.",Burning feet syndrome;Polyneuropathy;Wilson disease;adult;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;axonal injury/di [Diagnosis];burning feet syndrome/co [Complication];case report;clinical examination;clinical feature;copper blood level;fatty liver/di [Diagnosis];genetic screening;homozygosity;human;hypertransaminasemia;liver biopsy;male;nerve cell lesion/di [Diagnosis];nerve conduction;neurologic examination;point mutation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Rollnik, J. D.;Rost, I.;Marschall, C.;Wetzel, P.",2010,,,0,0,
1827,Overview and frontier for the development of metallopharmaceutics,"This review introduces the development of metal-containing pharmaceutics (metallopharmaceutics) such as anticancer agents containing platinum (Pt) and ruthenium (Ru), and superoxide dismutase (SOD) mimetic, focusing on the recent topics on antidiabetic vanadium (V) and zinc (Zn) complexes as well as antioxidative copper (Cu) and Zn complexes. From the ancient ages, people used many types of inorganic compounds to treat physical disorders or diseases. Since the modern concept of chemotherapy was achieved by Paul Ehrlich, who developed the arsenic (As)-containing compound to treat syphilis in 1910, a wide variety of metallopharmaceutics have been proposed and clinically used worldwide. This review is described for the researchers who are interested in the current states for the development of metallopharmaceutics. © 2010 The Pharmaceutical Society of Japan.",Anticancer;Antidiabetes;Antioxidative;Chemotherapy;Inorganic compound;Metallopharmaceutics;anemia/dt [Drug Therapy];antineoplastic activity;antioxidant activity;bacterial infection/dt [Drug Therapy];brain ischemia/dt [Drug Therapy];burn/dt [Drug Therapy];clinical trial;dermatitis/dt [Drug Therapy];diabetes mellitus/dt [Drug Therapy];drug absorption;drug binding site;drug bioavailability;drug design;drug protein binding;drug research;drug structure;glucose intolerance/dt [Drug Therapy];growth disorder/dt [Drug Therapy];human;hyperglycemia/dt [Drug Therapy];insulin resistance/dt [Drug Therapy];malignant neoplastic disease/dt [Drug Therapy];manic depressive psychosis/dt [Drug Therapy];non insulin dependent diabetes mellitus/dt [Drug Therapy];nonhuman;review;rheumatoid arthritis/dt [Drug Therapy];stomach ulcer/dt [Drug Therapy];structure analysis;syphilis/dt [Drug Therapy];unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];acetylsalicylate copper/dt [Drug Therapy];arsenic derivative/dt [Drug Therapy];arsphenamine/dt [Drug Therapy];auranofin/dt [Drug Therapy];aurothioglucose/dt [Drug Therapy];carboxyethylgermanium sesquioxide/dt [Drug Therapy];cisplatin/dt [Drug Therapy];copper complex/pd [Pharmacology];cyanocobalamin/dt [Drug Therapy];ebselen/dt [Drug Therapy];histamine/ec [Endogenous Compound];insulin/dt [Drug Therapy];lithium carbonate/dt [Drug Therapy];metal complex/pd [Pharmacology];metformin/ae [Adverse Drug Reaction];metformin/dt [Drug Therapy];platinum complex/pd [Pharmacology];polaprezinc/dt [Drug Therapy];ruthenium complex/dt [Drug Therapy];ruthenium complex/pd [Pharmacology];silver derivative/dt [Drug Therapy];sucralfate/dt [Drug Therapy];sulfadiazine silver/dt [Drug Therapy];superoxide dismutase/pd [Pharmacology];tetrathiomolybdic acid/dt [Drug Therapy];unindexed drug;vanadic acid/dt [Drug Therapy];vanadium derivative/dt [Drug Therapy];vanadium derivative/po [Oral Drug Administration];vanadium derivative/pk [Pharmacokinetics];vanadium derivative/pd [Pharmacology];vanadyl sulfate/ct [Clinical Trial];vanadyl sulfate/dt [Drug Therapy];vanadyl sulfate/po [Oral Drug Administration];zinc acetate/dt [Drug Therapy];zinc chloride/dt [Drug Therapy];zinc chloride/po [Oral Drug Administration];zinc chloride/pd [Pharmacology];zinc complex/dt [Drug Therapy];zinc complex/pd [Pharmacology],"Sakurai, H.",2010,April,,0,0,
1828,Encopresis and epilepsy: An unusual presentation of Wilson's disease,,abdominal radiography;adult;anorectal pressure;anxiety disorder;bradykinesia;case report;clinical feature;defecation;depression;diagnostic test;disease duration;drug dose escalation;Dubowitz Neurological Assessment;electroencephalogram;emotional disorder;epileptic discharge;feces incontinence/dt [Drug Therapy];focal epilepsy/dt [Drug Therapy];gait disorder;grand mal seizure/dt [Drug Therapy];human;hypersalivation;impulsiveness;laboratory test;letter;male;neuroimaging;neurologic disease;neuropsychological test;nocturnal enuresis;nuclear magnetic resonance imaging;outpatient department;symptom;tonic clonic seizure/dt [Drug Therapy];tremor;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];X ray;copper/dt [Drug Therapy];lamotrigine/do [Drug Dose];lamotrigine/dt [Drug Therapy];oxcarbazepine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Mirjana, K.;Srdjana, T.;Sanja, H.;Zeljko, K.;Miro, K.",2010,August,http://dx.doi.org/10.1016/j.yebeh.2010.06.013,0,0,
1829,Multi-elemental (Trace metals) analysis in serum and urine samples by dynamic reaction cell inductively coupled mass spectrometry,"Aim: Trace metals analysis plays an important part in occupational monitoring, assessment of exposure levels in poisoning as well as an aid in certain clinical diagnosis (Wilson's disease). Inductively coupled plasma mass spectrometry (ICP-MS) with cell reaction/collision capability that removes isobaric and polyatomic interferences has improved sensitivity and specificity in analysis. This study evaluates the performance of Perkin-Elmer ELAN DRC II instrument for analysis of serum (Al, Cr, Cu, Mn, Ni, Se, Zn) and urine (Al, As, Cd, Cr, Cu, Mn, Ni, Pb, Se, Zn) specimens, in preparation for clinical service introduction. Methods: Fresh gravimetric-preparations of standard (3-5 points; 20X dilution of PE Multi-Element Calibration Standard) for calibration of the ICP-MS were assayed in every batch run with analyses performed in standard or DRC (NH3) mode. Imprecisions (within-run, total-lab CVs) were assessed from daily triplicate analyses of quality control reagents (urine:Bio- Rad; serum:Seronorm) over a 5-days period. Detection limits were evaluated with replicates (n=10) of blank samples. Tmuo assess linearity, serial dilutions (5 points) were analysed with recoveries calculated. A comparison of serum/urine copper and serum zinc levels measured by ICP-MS and current laboratory atomic absorption spectrometry (AAS) was performed. Results: Calibration curves were linear through zero - fittings typically attained r2 0.990 - 0.999. Imprecision for withinrun results gave <10%CV for all elements in both serum and urine. Calculated total-lab CVs were low except for Al, Mn, Se having >15%CV indicating plausible wider variance of day-to-day calibration of these elements in each run. On standard mode, sensitivities were typically <0.1mug/L improving further with DRC mode. Linearity was verified for each element - up to 5 orders of magnitude from 0.01-200 mug/L. Comparative data with a limited sample size (n=30) showed reasonably similar levels of serum/urine copper (serum y=1.05x + 1.14, r-s 0.88; urine y=1.07x - 0.08, r-s 0.96) and serum zinc (y=1.31x - 1.45, r-s=0.85) levels by ICP-MS and AAS. Conclusions: ICP-MS with DRC mode showed promising multi-elemental analysis performance. Further work is needed to control variability in pre-analytical and analytical aspects of the protocol.",serum;urinalysis;mass spectrometry;urine;dilution;zinc blood level;Wilson disease;quality control;diagnosis;intoxication;exposure;sensitivity and specificity;monitoring;limit of detection;sample size;atomic absorption spectrometry;laboratory;trace metal;copper;zinc,"Tan, C. H. C.;Ng, W. Y.;Jacob, E.",2010,June,http://dx.doi.org/10.1177/20101058100190S201,0,0,
1830,Factors predicting neurological deterioration after chelation therapy in patients with Wilson's disease,"Background: There is paucity of information on the proportion of hepatic Wilson's patients who deteriorate on chelation therapy. There is also little information on factors that predict neurological deterioration. In this cohort study we intended to study what percentage of patients with hepatic Wilson's disease develop neuro deterioration on dpenicillamine. Our aim was to identify any prognostic factors which could predict neurological deterioration after the onset of chelation therapy. Methods: We enrolled newly diagnosed Wilson's disease patients in the age group between 3-18 yrs who had hepatic or combined hepatic with neurological manifestations. We excluded fulminant Wilson's and other causes of chronic liver disease. Evaluation of liver status was done using Child, MELD score and New Wilson's scoring index. We studied putative predictive factors like age, gender, and mode of presentation i.e. hepatic versus combined hepatic plus neurological. All patients were followed up to 2 yrs while on d-Penicillamine therapy. Results: One patient had combined clinical neurological involvement along with hepatic manifestation (10%). four of 10 patients (40%) had CNS lesions lesions on MRI brain at baseline evaluation.3 of 10 (30%) patients deteriorated neurologically with in follow up period. Factors like MELD score and INR are significantly abnormal (p=0.032 and 0.01 respectively) in those patients who deteriorated neurologically started on chelation therapy. Conclusions: One third patients of Wilson's disease who presented with hepatic or combined hepatic with neurological manifestations deteriorate on d-penicillamine therapy. Factors like MELD score and INR at the time of diagnosis are predictive factors for neurological deterioration in patients started on chelation therapy.",Indian;deterioration;patient;chelation therapy;human;society;gastroenterology;Wilson disease;therapy;liver;follow up;brain;chronic liver disease;groups by age;diagnosis;international normalized ratio;cohort analysis;gender;child;nuclear magnetic resonance imaging;central nervous system;penicillamine,"Reddy, N. R.;Puri, A. S.;Sachdeva, S.;Chaudhry, N.;Upreti, L.",2010,November,http://dx.doi.org/10.1007/s12664-010-0063-7,0,0,
1831,Effect of D-penicillamine on liver fibrosis and inflammation in wilson disease,"Introduction: Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients. METHODS: Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist. RESULTS: of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P < .05). CONCLUSION: D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.",liver fibrosis;inflammation;Wilson disease;transplantation;society;human;patient;fibrosis;liver;liver graft;fibrogenesis;liver injury;liver cell;bile;excretion;pathology;gene;male;female;mutation;scar;copper metabolism;diseases;penicillamine;copper;protein,"Kazemi, K.;Geramizadeh, B.;Kakaei, F.;Nikeghbalian, S.;Malekhosseini, S. A.",2010,27 Jul,,0,0,
1832,Spermidine/spermine actyltransferase is responsible for the metabolism of triethylenetetramine and other polyamine analogs in humans,"Triethylenetetramine (TETA), a copper II chelator traditionally used for the treatment of Wilson's disease, and a number of structural analogs are currently in clinical trials for cancer. However, the metabolism of TETA has never been thoroughly investigated, which is crucial for its further development in cancer treatment. The two major metabolites of TETA found in humans are N1-acetyl-TETA (MAT) and N<sup>1</sup>, N<sup>10</sup>-diacetyl-TETA (DAT). Traditionally, acetylation of drug is thought to be catalyzed by N-acetyltransferase (NAT2). FDA requires that pharmacological properties of any drug metabolized via acetylation route have to be investigated in population with different NAT2 phenotype. However, our recent clinical study showed that there was no significant difference in pharmacokinetic, pharmacodynamic and metabolites profiles of healthy volunteers with fast or slow NAT2 acetylation phenotype. We therefore hypothesize that the enzyme responsible to TETA acetylation is spermidine/spermine acetyltransferase (SSAT), which has never before been considered as a drug metabolizing enzyme, rather than the NAT2. We carried out in vitro drug metabolism assays to pin-point the enzyme responsible for TETA metabolism. TETA and MAT (as substrate) and acetyl-coenzyme A were incubated with human liver microsome and cytosol from 5 individuals in the presence or absence of pentamidine or acetaminophen separately. The formation of MAT from TETA and DAT from MAT was detected and measured using our LC-MS method published previously. Both liver microsome and cytosol could catalyze the biotransformation of TETA and MAT. The rate of metabolism in microsome and cytosol within each individual varies. The rates of metabolism in microsome and cytosol also varied between individuals (Km range 223 - 909 M, V<inf>max</inf> range 96 - 482 pg/min/mg protein). Pentamidine, a specific inhibitor for x SSAT, could inhibit the reaction and increase Km by over 30%. While acetaminophen, a specific inhibitor for NAT2, did not show any inhibition effect. Same experiments had been performed in rat liver microsome and cytosol, and similar results were obtained apart from the Km and V<inf>max</inf> values. TETA and two other analogs of polyamine, diethylnorspermine and diethylspermine, all of which are under investigation for the treatment of cancer, were incubated with pure whole-recombinant human SSAT protein, and formation of acetylated metabolites were found. The identification of SSAT, which has never been before considered to be a xenobiotic metabolizing enzyme, as the enzyme to catalyze the actylation of polyamine analogs, have a significant importance in the clinic, especially in clinical trial situations. Many polyamine analogs have been developed as potential cancer drugs and many of them, including TETA, are being investigated in clinical trials. Finding the right enzyme (i.e. SSAT instead of traditional NAT2) to study their biotransformation is crucial for understanding their pharmacology, which is essential for the overall drug study.","human;cancer research;metabolism;cytosol;acetylation;clinical trial (topic);neoplasm;liver microsome;metabolite;microsome;phenotype;biotransformation;drug metabolism;cancer therapy;hospital;rat;normal human;clinical trial;pharmacokinetics;clinical study;population;liver;assay;pharmacology;in vitro study;Wilson disease;food and drug administration;trientine;polyamine;enzyme;paracetamol;pentamidine;protein;acyltransferase;copper;2,3 butanedione;drug metabolizing enzyme;acetyl coenzyme A;xenobiotic agent;chelating agent","Lu, J.;Li, M.;Xu, H.;Tingle, M.;Cooper, G. J. S.",2010,,http://dx.doi.org/10.1158/1538-7445.AM10-LB-287,0,0,
1833,Wilson France: A national database for Wilson's disease,"Introduction: Wilson's disease (WD) is a rare inherited disease with an efficient treatment if initiated early. Improving the knowledge of this disease is a priority of the French national Centre of Expertise for a better access to diagnosis and treatment. This national organisation created a database. Objective: Improve the knowledge of WD by an epidemiological study on the French cohort. Methods: We registered all patients followed by all the French centres working with the national Centre of Expertise. Results: Since 2006, 281 patients (1-73 year old) were included in the Wilson France database (sex ratio: 1). Mean age at diagnosis was 19 years. First symptoms were neurological for 36% of the patients, hepatic for 38%, renal, psychiatric or hematologic for 11%. Fifteen percent were diagnosed after familial screening. At time of diagnosis, Kayser-Fleischer ring was observed in 95% of patients with neurological symptoms, in 55% of hepatic presentations and in 26% of the presymptomatic forms. Mean coeruloplasminemia was low (0.08 g/L) but 5% of patients had normal values (>0.2 g/L). Mean urinary copper was increased in 96% of the patients. Genetic investigation was not conclusive in 15.9 % of the families (only one or no mutation found). First treatment was D-Penicillamine in 85% of the cases and after a mean follow up of 15 years, the treatment was D-Penicillamine for 44.4% of the patients, Trientine for 14.4%, Zinc for 26.7%, association of chelator and zinc for 5.6 %; 5.6 % of the patients had liver transplantation. Discussion: The database included approximately 1/3 of the Wilson disease patients in France. In order to improve the recruitment of Wilson's disease patients, coordination of all health professionals with a multidisciplinary approach is necessary. This work is realised in collaboration with Eurowilson database.",rare disease;France;data base;Wilson disease;human;patient;diagnosis;mutation;follow up;normal value;liver transplantation;neurologic disease;screening;health practitioner;sex ratio;zinc;penicillamine;trientine;copper;chelating agent,"Trocello, J. M.",2010,,,0,1,
1834,Elevation of liver enzymes in a 6 year old boy with severe hemophilia A leading to presymptomatic diagnosis of Wilson disease,"We report on a 6 year old boy with severe hemophilia A (inversion of intron 22 of the FVIII gene) in whom moderately increased levels of liver enzymes (AST and ALT) were repeatedly found on routine check-up. No common cause for hepatitis (hepatitis B or C, CMV, EBV) was found, but further evaluation revealed decreased serum ceruloplasmin concentration. The 24 hour urinary copper excretion was significantly increased. The diagnosis of Wilson disease was proven by the demonstration of compound heterozygosity for ATP7B gene mutations (R1041W and N1270S); parents were heterozygous. Apart from elevation of transaminases, no signs of liver dysfunction, no neurologic signs, and no Kayser-Fleischer ring was detected; ultrasound showed enlargement of liver but a normal parenchymal structure. Therapy with D-penicillamine and vitamin B6 was started and monitored by 24 hour urinary copper excretion and measurement of transaminases. Wilson disease is an autosomal-recessive disorder of copper metabolism that results in accumulation of copper in liver, brain, kidney and cornea and can lead to hepatic and neuropsychiatric dysfunction. Even a mild but constant elevation of transaminases can indicate Wilson disease. Presymptomatic diagnosis offers the opportunity of early therapy with D-penicillamine or zinc acetate. Therefore, plasma ceruloplasmin and urinary copper excretion should be investigated in cases of chronic elevation of liver enzymes.",hypertransaminasemia;boy;male;human;hemophilia A;diagnosis;Wilson disease;excretion;liver;ceruloplasmin blood level;therapy;hepatitis B;hepatitis;ultrasound;neurologic disease;liver dysfunction;parent;gene mutation;heterozygosity;cornea;kidney;autosomal recessive disorder;copper metabolism;brain;gene;intron;copper;penicillamine;vitamin;liver enzyme;aminotransferase;zinc acetate,"Hainmann, I.;Woltering, T.;Greiner, P.;Superti-Furga, A.;Zieger, B.",2010,,,0,0,
1835,Wilson's disease masquerading as hepatic hydrothorax in a young female,"Purpose: Wilson's disease (WD) is a rare genetic disorder of copper metabolism with a hepatic or neurological presentation. Histopathological findings of hepatic involvement vary from steatosis to end stage cirrhosis. WD presenting as acute or fulminant liver failure, hemolytic crisis, neuropsychiatric symptoms and rarely decompensated cirrhosis has been described. This is the first case of WD presenting as worsening dyspnea secondary to right hepatic hydrothorax. Case Report: A 20-year-old Caucasian female was admitted with progressive dyspnea for six months. She had no history of significant alcohol abuse or risk factors for viral hepatitis. Physical exam revealed mild icterus, right pleural effusion, ascites and peripheral edema. Kayser-Fleischer rings were not seen on slit lamp exam. Laboratory results revealed mildly elevated transaminases and bilirubin, low albumin, coagulopathy and thrombocytopenia. Computed tomography showed massive right-sided hydrothorax with mediastinal shift , ascites and liver cirrhosis. Echocardiogram was normal. A right sided chest tube was placed resulting in high output (> 15 L) drainage of transudative fluid and relief of symptoms. Further evaluation was notable for a low serum ceruloplasmin level of <10 mg/dl and a high 24 -hour urine copper (Cu) level of 270 mug. Liver biopsy showed micro and macro vesicular steatosis with active cirrhosis but could not quantitatively measure Cu due to lack of sufficient specimen. Rhodanine stain for Cu was positive in one of the nodules. While awaiting biopsy results the patient developed tremors and worsening liver function. Magnetic resonance imaging of the brain showed increased signal intensity in the globus pallidus consistent with lenticular deposition of Cu. Diagnosis of WD was made. She was started on Trientene and Zinc and transferred to a liver transplant center where she underwent successful liver transplantation. Discussion: Out of 50 % of patients with WD that present with liver disease only 3 % have hepatic decompensation on presentation. Hepatic hydrothorax is an even rarer complication and is defined as a significant pleural effusion, usually > than 500 mL, in a cirrhotic patient in the absence of cardiopulmonary disease. Pathophysiology involves leakage of ascitic fluid from the peritoneal cavity into the pleural space through the embryologic defects, which are more prevalent in the right hemidiaphragm. Decompensated cirrhosis due to WD can be managed with medical therapy. Patient's who fail treatment and those with hepatic hydrothorax will require liver transplantation. A high index of clinical suspicion is needed for early diagnosis and medical management.",gastroenterology;college;female;hydrothorax;human;patient;decompensated liver cirrhosis;liver cirrhosis;pleura effusion;liver transplantation;steatosis;dyspnea;ascites;Caucasian;jaundice;case report;virus hepatitis;fulminant hepatic failure;thrombocytopenia;computer assisted tomography;echocardiography;ceruloplasmin blood level;liver biopsy;hypertransaminasemia;liver disease;peritoneal cavity;therapy;blood clotting disorder;risk factor;tube;liquid;laboratory;urine;brain;slit lamp;alcohol abuse;nuclear magnetic resonance imaging;liver function;peripheral edema;tremor;globus pallidus;diagnosis;liver graft;biopsy;stain;pathophysiology;ascites fluid;pleura cavity;hemidiaphragm;early diagnosis;disease management;copper metabolism;genetic disorder;rhodanine;albumin;bilirubin;copper;zinc,"Ghayam, S.;Ponugoti, S.;Pawa, S.",2010,October,http://dx.doi.org/10.1038/ajg.2010.320-7,0,0,
1836,Late-onset neurological Wilson's disease without K-F rings or characteristic MRI findings,"Objective: Report an unusual case of genetically confirmed Wilson's disease (WD) presenting as late-onset parkinsonism without K-F rings or characteristic brain MRI abnormalities. Background: The age of onset of WD is variable but, generally occurs in the 2nd or 3rd decade. A neurological presentation is rare beyond 40 years and has not been reported without K-F rings or characteristic brain MRI findings. As a result, screening for WD in patients presenting with a movement disorder is not routine after this age and it remains unclear what the upper limit is for age of neurological phenoconversion. Methods: Case Report. Results: A 50 year old man presented with a 15 month history of left hand tremor, left arm stiffness, insomnia and anxiety. Examination showed predominantly left sided parkinsonism with resting tremor, rigidity and bradykinesia. K-F rings were absent. Quetiapine and olanzapine were briefly used to treat anxiety after the onset of motor symptoms but, were discontinued at least 2 months prior to presentation. Parkinsonism was subsequently unresponsive to ropinirole, pramipexole and only minimally responsive to levodopa up to 200mg TID. Investigation included a normal brain MRI and normal EEG. Two years later, a low serum ceruloplasmin of 4.1 was unexpectedly found as part of a research project. Repeat studies at a commercial lab were ceruloplasmin 7.4 mg/dL (25-63), serum copper 28 g/dL (70-150), urine copper 65 g/24 hours (3-35). Iron studies and LFTs were normal. Formal ophthalmological exam did not reveal K-F rings. ATP7B gene sequencing (Mayo Clinic) revealed 2 different known pathogenic WD mutations (compound heterozygote). The patient was treated with zinc for 6 months without improvement. A liver biopsy revealed increased copper without cirrhosis and a repeat slit lamp examination at an academic medical center failed to reveal K-F rings. Current treatment is Trientine. Conclusions: The diagnosis of WD was made fortuitously after a low serum ceruloplasmin was found as part of a research project. This case suggests that late-onset WD is more common than previously thought and expands the range of phenotypic expression to include parkinsonism presenting in later adulthood without the presence of K-F rings or MRI abnormalities. Screening for WD with a serum ceruloplasmin should be routine in patients presenting with parkinsonism, tremor or dystonia in later life.",Parkinson disease;nuclear magnetic resonance imaging;Wilson disease;etiology;motor dysfunction;pathogenesis;parkinsonism;ceruloplasmin blood level;patient;brain;tremor;screening;rigidity;anxiety;slit lamp;university hospital;diagnosis;adulthood;dystonia;onset age;case report;male;hand;hand tremor;arm;insomnia;examination;bradykinesia;copper blood level;urine;gene sequence;hospital;mutation;heterozygote;liver biopsy;liver cirrhosis;electroencephalogram;copper;trientine;quetiapine;olanzapine;ropinirole;pramipexole;levodopa;ceruloplasmin;iron;zinc,"Molho, E. S.",2010,30 Apr,http://dx.doi.org/10.1002/mds.23126,0,0,
1837,Novel angiogenesis inhibitor tetrathiomolybdate enhances the tumor cell killing efficacy of oncolytic virus,"Oncolytic viruses (OV) are modified viruses specifically designed to lyse cancerous cells while leaving surrounding tissue intact. Although effective in killing tumors, OV therapy has shown limited effectiveness against glioma in clinical trials. Tumor microenvironment potentially hinders OV propagation and spread; particularly, the angiogenic and inflammatory responses following OV inoculation have been demonstrated to significantly limit OV efficacy. Copper supports angiogenesis, and its physiological level has been shown to inhibit the infection and replication of wild-type HSV. The goal of our current project is to determine whether copper-chelating agent, tetrathiomolybdate, can be used to enhance overall OV efficacy in malignant glioma. Tetrathiomolybdate is already approved by the U.S. Food and Drug Administration for the treatment of Wilson's disease and is currently being evaluated for safety and efficacy. Previous findings indicate that the anticancerous effects of OV can be significantly increased by pretreatment with an angiostatic agent. The angiostatic and immunosuppressive properties of tetrathiomolybdate make it an ideal candidate to enhance OV therapy. To confirm this, we tested whether copper inhibits OV-mediated glioma cell killing, and tetrathiomolybdate can be countereffective. We found that copper at physiological concentration in serum could significantly inhibit glioma cell killing and virus replication. This inhibition of cell killing by OV incubated with copper was observed in multiple different OV tested. Viral replication and cytotoxicity assay data showed that tetrathiomolyb-date-mediated copper chelation could rescue copper-inhibited viral replication, leading to improved tumor cell killing effect. On the basis of these results, we tested therapeutic efficacy of combing tetrathiomolybdate with OV against a U251T3 subcutaneous glioma model. We found a significant increase in the antitumor response of animals treated with tetrathiomolyb-date plus OV compared with animals treated with OV alone. Collectively, our results indicate that the combination of tetrathiomolybdate and OV enhances elicits a potent efficacy profile compared with OV alone, suggesting concurrent administration of tetrathiomolybdate to patients may improve the OV efficacy.",cell killing;tumor cell;oncology;society;therapy;virus replication;glioma;glioma cell;tumor microenvironment;inflammation;inoculation;angiogenesis;infection;wild type;glioblastoma;United States;cytotoxicity;food and drug administration;safety;serum;assay;chelation;model;patient;human;virus;tissue;tumor;clinical trial (topic);Wilson disease;oncolytic virus;tetrathiomolybdic acid;angiogenesis inhibitor;copper;chelating agent,"Yoo, J. Y.;Pradarelli, J.;Kaka, A.;Alvarez-Breckenridge, C.;Pan, Q.;Teknos, T.;Chiocca, E. A.;Kaur, B.",2010,November,http://dx.doi.org/10.1093/neuonc/noq116,0,0,
1838,Wilson's diseases: Single center's 1 year overall experience,"Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. This rare disease is caused by mutations in the gene encoding a copper-transporting P-type ATPase, which is important for copper excretion into bile, leading to copper accumulation in the liver. Toxic copper concentrations can also be found in the brain and kidney, and clinical phenotypes include hepatic, haemolytic, neurologic and psychiatric diseases. WD has a wide spectrum of clinical manifestations. Affected children may be entirely asymptomatic and the diagnosis problematic. The objective of this study is to present our single center experience over one year with WD, underlying his different presentations. Patients and methods: In the last 12 months (from april 2009 to april 2010) 5 patients (3 males) fulfilled criteria for the diagnosis of WD. Evaluation included detailed physical examination, conventional laboratory testing (urinary copper excretion, levels of serum ceruloplasmin), genetic analysis, and liver biopsy. 3 patients presented isolated liver disease, 1 had mixed neurological and hepatic involvement and 1 presented with acute liver failure. All 3 patients with cirrothic liver underwent orthotopic liver transplantation (OLT). Results: The median age at diagnosis of WD was 10.8 (range, 7-16). All patients had hepatic manifestations of the disease when diagnosed: cirrhosis (2), chronic hepatitis (2) and fulminant hepatic failure (1). Two patients were asymptomatic at diagnosis. 1 of the symptomatic patients presented the typical neurological symptoms, first with changes in behaviour and deterioration in schoolwork evolving to lack of motor coordination, drooling, dysarthria, dystonia, and spasticity with the deeping of the disease. At diagnosis, just the patient with neurological manifestation had positive Kayser Fleischer ring. Serum ceruloplasmine levels were decreased in all patients, median value 9.2 mg/dl (range 2-16), with lower levels in cirrhotic patients. The 24-h excretion of copper in urine was raised in all patients, >75 mug/24 hours before (median value 360 mug/24) or >1400 mug/24 hours after penicillamine challenge. Genetic analysis showed double eterozighosis in 3/5, the other 2 patients had just 1 recognized mutation. As diagnostic important proved all patients had the copper content of more than 250 mug/g hepatic dry weight. We started zinc therapy (zinc acetate) in all the patients at the time of diagnosis, just in the one with neurological symptoms with added a copper chelator drug as Trientine. None of 3 cirrhotic patients recovered with therapy and avoided liver transplantation. In the 2 asymptomatic patients zinc acetate therapy was started and well tolerated. In those 2 patients liver function tests showed improvement after 3 weeks of therapy reaching normal values in 2 months for both. The indication for liver transplantation was acute on chronic (2/3) or fulminant, liver failure (1/3). The median follow-up after liver transplantation was 1 year, 1 patient died for perioperative complications (66% patient survival). Copper metabolism returned to normal in all patients. None of the transplanted patients with exclusive liver disease required chelation treatment after liver transplantation and none developed neurological symptoms of Wilson's disease. Conclusion: Detection of WD in children remains very difficult also due low frequency of cases, however our 1 year experience show higher frequency than reported in the literature. The most important investigation is liver biopsy with the assessment of liver copper. Genetic analysis may help in doubtful cases. Ceruloplasmine, haemoglobin, ALT, ALP and plasma albumin were significantly different between fulminant and non-fulminant WD and could be used as indirect markers in evaluation of urgent OLT. It is important to be aware of the different manifestations of Wilson's disease in the pediatric population, in order to make appropriate evaluations in a timely manner to facilitate early diagnosis, to ensure appropriate treatment and to avoid the ri k of underestimate it.",patient;diagnosis;liver transplantation;therapy;excretion;liver;genetic analysis;neurologic disease;Wilson disease;liver disease;copper metabolism;fulminant hepatic failure;mutation;child;liver biopsy;population;early diagnosis;risk;autosomal recessive disorder;gene;bile;brain;kidney;phenotype;mental disease;male;physical examination;laboratory;ceruloplasmin blood level;isolated liver;acute liver failure;liver cirrhosis;chronic hepatitis;deterioration;motor coordination;hypersalivation;dysarthria;dystonia;spasticity;serum;urine;dry weight;liver function test;normal value;follow up;perioperative complication;survival;chelation;rare disease;copper;zinc acetate;ceruloplasmin;serum albumin;marker;copper exporting adenosine triphosphatase;chelating agent;penicillamine;zinc;trientine;hemoglobin,"Pietrobattista, A.;Candusso, M.;Alterio, A.;Sartorelli, M.;Francalanci, P.;Comparcola, D.;Nobili, V.;Torre, G.",2010,October,,0,1,
1839,Hepatocellular cancer in neurological wilson's disease,"Background: Hepatocellular cancer (HCC) in Wilson's disease with cirrhosis is extremely unusual. Liver copper is supposed to be a protective factor against carcinogenesis. Patients presenting with neurological Wilson's disease are rarely monitored for tumours. Case report: A 30 year old male was diagnosed 4 years previously with neurological Wilson's disease on the basis of clinical features, presence of a K-F ring, elevated urinary copper levels and a positive penicillamine challenge test. His liver function tests were normal. He was aggressively treated with D- penicillamine and Zinc with significant improvement in neurology and lightening of the K-F ring. Six months prior he was investigated for right upper quadrant discomfort. A hepatocellular cancer measuring 10cm was detected in the right posterior sector of the liver. HCV RNA, HBsAg, Anti HBc, HBV DNA, ANA were all negative. We performed a segment VII/ VIII resection from which the patient recovered uneventfully. A moderately differentiated HCC in the setting of cirrhosis was confirmed on histology. Interestingly, the liver copper levels were very low, presumably due to aggressive chelation therapy. Discussion: Liver copper is protective in Wilson's disease. Reports of HCC in Wilson's disease are extremely rare, especially in those presenting with neurological Wilson's disease and no hepatic manifestations. In previous reports, hepatits may co-exist, or has not been ruled out. In the present case, Hepatitis B and C were ruled out. We postulate that aggressive chelation therapy cleared the liver of protective copper leading to carcinogenesis.",Wilson disease;neoplasm;liver;chelation therapy;carcinogenesis;patient;liver cirrhosis;surgery;histology;hepatitis B;case report;male;clinical feature;provocation test;liver function test;neurology;copper;penicillamine;hepatitis B core antibody;alprazolam;dna;zinc;hepatitis B surface antigen;rna,"Shah, S.",2010,April,http://dx.doi.org/10.1111/j.1477-2574.2010.00165.x,0,0,
1840,CD8 T cell lymphopenia and functional asplenia in an infant with impaired neural crest development associated with ZEB2 mutation and Mowat Wilson syndrome (MWS),"Introduction: We report abnormal immune findings in a patient with a zinc finger protein deficiency and MWS Case Description: A 2.5 year old male with Hirschprung's disease and MWS presented for evaluation of asplenia. MWS was diagnosed at birth with genetic testing demonstrating chromosome 2q22.3 mutation and ZEB2 deficiency. At 2 days of life, a small spleen was noted and PCN prophylaxis started. No history of serious infections were reported except enterocolitis at age 1. Killed childhood vaccinations were up to date; the patient never received live viral vaccines. Immune evaluation revealed CBC with mildly elevated eosinophil count. Peripheral smear confirmed asplenia. Serum immunoglobulins revealed low IgA and IgM but normal IgG and IgE. Oxidative burst assay was normal. Serologic vaccine responses showed 2 of 7 protective antibody levels to Prevnar vaccine and indeterminate response to tetanus. Lymphocyte phenotyping revealed low CD3+ T cells, low levels of CD3+CD8+ T cells (3.9%; normal lower limit of 16.0%) but normal levels of CD3+CD4+ T cells. B cell, Natural Killer cell, and HLA-DR measurements were appropriate. T cells demonstrated adequate response to mitogen and antigen stimulation. Four weeks after revaccination (Prevnar 13, DTaP), protective antibody levels of all 13 pneumococcal serotypes, tetanus, diphtheria and haemophilus were demonstrated. Repeat lymphocyte phenotyping again showed low CD3+ T cells and low CD3+CD8+ T cells. Evaluation for latent viral infection was negative. Discussion: ZEB2 is the zinc finger E-box binding homeobox 2 gene responsible for embryonic development of neural crest cells. CD8 homeostasis is not defined but abnormalities in CD8 cell expression have been reported in MHC Class I deficiency, ZAP 70 deficiency and IL-7 deficiency. Our patient does not appear to have IL-7 perturbations as CD3+CD4+ cells are present in normal number; there is no evidence of MHC Class I deficiency. ZAP 70 deficiency, another zinc finger deficiency, presents with T cell dysfunction not seen in this patient. Neurologic disorders have been linked with immune deficiency, e.g. ataxia telangiectasia, ADA deficiency, Chediak-Higashi syndrome. Patients with MWS (impaired neural crest development) should be evaluated for evidence of immunologic abnormalities including asplenia.",T lymphocyte;infant;Wilson disease;asplenia;college;mutation;neural crest;lymphocytopenia;immunology;allergic asthma;patient;tetanus;lymphocyte;phenotype;adenosine deaminase deficiency;Chediak Higashi syndrome;protein deficiency;male;genetic screening;chromosome 2;spleen;prophylaxis;enterocolitis;childhood;vaccination;eosinophil count;smear;immunoglobulin blood level;infection;respiratory burst;B lymphocyte;natural killer cell;assay;immunostimulation;revaccination;diphtheria;Haemophilus;virus infection;homeobox;gene;embryo development;neural crest cell;homeostasis;neurologic disease;ataxia telangiectasia;immune deficiency;CD8 antigen;CD3 antigen;zinc finger protein;Pneumococcus vaccine;CD4 antigen;protein kinase ZAP 70;antibody;vaccine;virus vaccine;immunoglobulin A;immunoglobulin M;immunoglobulin G;immunoglobulin E;mitogenic agent,"Shroff, P.;Potocki, L.;Chinen, J.;Hanson, I. C.",2010,November,,0,0,
1841,An unexpected novel antioxidant-like activity for the classic copper-chelating drug penicillamine,"Penicillamine (beta, beta'-dimethylcysteine) has been widely used clinically as a copper-chelating drug for the treatment of copper overload in Wilson's disease. In this study, we found that penicillamine provided marked protection against cytotoxicity induced by tetrachlorohydroquinone (TCHQ, a major toxic metabolite of the widely used wood preservative pentachlorophenol) in human fibroblasts, while other copper chelators such as BCS (bathocuproine disulfonate) and trientine do not. The autooxidation process of TCHQ yielding the reactive tetrachlorosemiquinone (TCSQ) radical was studied by ESR and UV-visible spectral methods. Interestingly and surprisingly, the formation of TCSQ radical was found to be dramatically delayed by penicillamine in a concentration dependent manner. In contrast, penicillamine disulfide (the oxidized form of penicillamine), N-acetylpenicillamine, BCS and trientine had no detectable effect on TCHQ autooxidation. HPLC-MS studies showed that TCSQ radical was reduced to TCHQ by penicillamine, which was concurrently oxidized to its corresponding disulfide form. These data indicate that the protective effects of penicillamine on TCHQ-induced cytotoxicity were not due to its binding of copper, but rather to its reduction of the reactive TCSQ radical to the much less reactive TCHQ. This is the first report demonstrating an unexpected novel antioxidantlike activity for this classic copper-chelating amino thiol drug, which might prove highly relevant to the biological activities of penicillamine.",society;cytotoxicity;autooxidation;protection;human;Wilson disease;fibroblast;biological activity;high performance liquid chromatography;penicillamine;copper;free radical;antioxidant;trientine;toxin;wood protecting agent;thiol;chelating agent;penicillamine disulfide;n acetylpenicillamine;disulfide;pentachlorophenol;tetrachlorohydroquinone,"Zhu, B. Z.;Mao, L.",2010,,http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.595,0,0,1747
1842,Copper disrupts nuclear receptor function in Wilson's disease,"Wilson's disease is an autosomal recessive disease due to mutations in the Cu-transporting P-type ATPase (ATP7b) that results in excessive hepatic copper accumulation and is associated with steatosis, cholestasis, cirrhosis, and liver failure. The Wilson's disease animal model (Atp7b-/-) has decreased expression of several hepatic nuclear receptor signaling pathways, including decreased FXR:RXR target gene expression. Methods: DNA binding was measured by Electrophoretic Mobility Shift Assays (EMSA) with the following: in vitro translated FXR and RXR proteins synthesized with copper (CuSO4) and/or zinc (ZnSO4) (1-40 muM); nuclear extracts from HepG2 cells treated for 16 hours with 75 muM CDCA, +/- metals (5 muM CuSO4 and/or 40 muM ZnSO4); and nuclear extracts from control and Atp7b-/- mice. Total RNA was harvested from HepG2 cells (as stated above) and gene expression [bile salt export pump (BSEP, Abcb11), metallothionein (Met) 2, FXR, and TNFalpha] measured by real-time PCR. Results: In vitro translation of RXR with 4-40 muM CuSO4 resulted in complete loss of FXR:RXR binding to the SHP and BSEP promoters, and the addition of 40 muM ZnSO4 to the reaction restored binding to the SHP and BSEP promoters. Protein expression of FXR and RXR was not decreased by metal in the in vitro translation reaction (measured by Western blot and S35-methione incorporation). Binding of FXR to the BSEP and SHP promoters in liver nuclear extracts was decreased in Atp7b-/- mice; however, binding of the NFkappaB (non-zinc finger transcription factor) or the SP1 (nonnuclear receptor zinc finger transcription factor) complex was not different between control and Atp7b-/- mice. In HepG2 cells, CuSO4 treatment decreased CDCA induction of BSEP mRNA expression by 80% (P<0.05), which was restored to 40% (P<0.05) of CDCA treatment alone, by the addition of ZnSO4 to cultures containing CuSO4 and CDCA. Met2 mRNA expression was significantly increased 2- (P<0.05, CDCA treatment), 7- (P<0.05, CuSO4 treatment), and 50-fold (P<0.01, CDCA+CuSO4+ZnSO4 treatment) in HepG2 cells. FXR and TNFalpha mRNA expression were not changed with CuSO4 treatment. Also, CuSO4 treatment of HepG2 cells eliminated nuclear extract binding to the BSEP promoter. Conclusions: Copper disrupts nuclear receptor binding activity, and decreases hepatic target gene expression. DNA-binding experiments in models of excess copper suggest that copper displacement of zinc in the zinc-finger of nuclear receptors promotes the pathology of Wilson's disease, and the addition of excess zinc may ameliorate negative effects of copper on nuclear receptor activity.",Wilson disease;liver;liver disease;promoter region;mouse;in vitro study;gene expression;DNA binding;gel mobility shift assay;liver cirrhosis;cholestasis;pump;steatosis;real time polymerase chain reaction;protein expression;Western blotting;mutation;liver failure;autosomal recessive disorder;receptor binding;binding affinity;model;animal model;pathology;copper;cell nucleus receptor;zinc;zinc finger protein;messenger RNA;dna;transcription factor;metal;protein;rna;bile salt;adenosine triphosphatase;receptor;metallothionein II,"Wooton-Kee, C. R.;Moore, D. D.;Lutsenko, S.",2010,October,http://dx.doi.org/10.1002/hep.23990,0,0,
1843,Iron and the HFE-gene in Wilson disease,"Introduction: Wilson Disease (WD) is an inherited disorder of copper metabolism, leading in untreated patients to liver failure and progressive neurological deterioration. Animal studies and several case reports suggested a hepatic iron overload or alterations in iron processing in WD. In line with these findings a significantly higher HFE-mutation frequency was reported in small series of WD patients. The aim of the current study was the assessment of iron metabolism and HFE gene frequencies in WD patients as well as and analysis of treatment effects due to chelation therapy. Patients and methods: Data of 143 WD patients treated at the university hospital Heidelberg between 1968 and 2009 were analzysed retrospectively. Parameters of clinical presentation, liver function and iron metabolism were recorded. EDTA Blood samples of the patients were analyzed for alterations in the HFE gene (H63D; C282Y) using standard RT-PCR technices. Results: Contrary to previous reports in our large collective of WD patients allel frequencies of HFE gene mutations (HFE mutation in 143 patients: 120 wild type, 3 C282Y-heterozygous, 1 C282Y-homozygous, 16 H63D-heterozygous, 2 H63D-homozygous and 1 H63D/C282Y-compound- heterozygous) were 2,1% for C282Y and 7,3% for H63D and though in line with the frequencies obtained for general population. Mutations of the HFE-gene were no predictors for an early clinical manifestation or a fulminant clinical course of Wilson Disease. To further elucidate the role of reduced coeruloplasmine (CP) levels and deficiency of its ferro-oxidase activity, patients were subgrouped according to their CP levels. Patients with distinct hypoceruloplasminemia (CP < 0,1 g/l) showed elevated ferritin and lowered transferring (p<0.05). In our cohort different treatment regimens (D-penicillamine, trientine, zinc or combination therapy with a chelating agent and zinc) did not alter parameters of iron metabolism Discussion: Hypoceruloplasminemia seems to have only a slight impact on the parameters of the iron metabolism, despite the diminished ferroxidase activity of ceruloplasmin. HFE-gene mutations can be additional risk factors for a clinically significant iron overload in individual cases, but allel frequencies indicate no association between WD and hereditary HFE-related hemochromatosis. Effects of chelation therapy for WD on iron metabolism seem to be minor and in most cases without clinical relevance.",liver;liver disease;gene;Wilson disease;patient;iron metabolism;mutation;chelation therapy;iron overload;gene mutation;processing;mutation rate;gene frequency;university hospital;liver function;case report;wild type;population;disease course;blood sampling;therapy;risk factor;hemochromatosis;copper metabolism;liver failure;deterioration;animal experiment;iron;ceruloplasmin;zinc;oxidoreductase;flurothyl;ferritin;penicillamine;trientine;chelating agent;edetic acid,"Pfeiffenberger, J.;Gotthardt, D.;Seessle, J.;Herrmann, T.;Stremmel, W.;Weiss, K. H.",2010,October,http://dx.doi.org/10.1002/hep.23979,0,0,
1844,Alterations of lipid metabolism in Wilson disease,"Background: Wilson disease (WD) is an inherited disorder of copper metabolism, leading to toxic copper accumulation in the liver, brain and other tissues. The development of a hepatic steatosis is a common symptom in early stages. Animal models (ATP7b-/- and LEC rats) show changes in lipid metabolism as the amount of triglycerides and cholesterol in serum are decreased. Alterations of lipid metabolism in humans have not been intensivley investigated in WD so far, but former studies suggested an influence of specific WD treatment. Under zinc therapy a decrease of total cholesterol and high-density lipoprotein (HDL) raises the question, whether this treatment might be atherogenetic. PATIENTS AND METHODS: 251 WD patients, treated at the university hospital Heidelberg between 1990 and 2009 were retrospectively reviewed. Patients were subgrouped by sex, treatment (DPA, trientine or zinc) or manifestation (hepatic, neurological, mixed and asymptomatic) for analysis of course of disease and laboratory values (including serum lipid profile, triglycerides, cholesterol, HDL, LDL, lipoprotein (a), serum bile acids, adiponectin and leptin). The occurance of vascular events under therapy and the prevalence of coronary heart disease were recorded. Results: Serum lipids were statistically not different between males and females, neither in treated or untreated patients. Interestingly in therapy naive patients cholesterol levels were decreased in hepatic patients with a median of 158 (66-319) mg/dl vs. neurological 194 (123-243) mg/dl or mixed 186 (145-244) mg/dl or asymptomatic patients 195 (173-294) mg/dl. Under treatment of at least 12 months these differences diminished. Contrary to former studies, we did not observe a decrease of total cholesterol or HDL under zinc treatment or chelator based therapy. Vascular events were rare and did not statistically differ between treatment groups or between patients with different manifestations. However serum lipoprotein (a) was remarkably higher in neurologic affected patients than in patients with perdominant liver disease. CONCLUSION: Only minor changes in the serum lipid profile of WD patients were found, that were diminished under therapy. In contrast to animal models of the disease the amount of triglycerides and cholesterol was not decreased. Our data suggest no significant atherogenetic effects of medical treatments for WD.",liver;lipid metabolism;liver disease;Wilson disease;patient;therapy;lipid blood level;animal model;cholesterol blood level;bile acid blood level;prevalence;ischemic heart disease;male;female;copper metabolism;brain;tissue;fatty liver;Long Evans cinnamon rat;serum;human;university hospital;laboratory;lipoprotein blood level;high density lipoprotein;cholesterol;triacylglycerol;zinc;low density lipoprotein;leptin;chelating agent;copper;trientine;high density lipoprotein cholesterol;adiponectin;lipoprotein A,"Seessle, J.;Gohdes, A. M.;Gotthardt, D.;Pfeiffenberger, J.;Stremmel, W.;Weiss, K. H.",2010,October,http://dx.doi.org/10.1002/hep.23979,0,0,
1845,The Toronto Western Hospital Wilson's disease study: Perspectives from an adult urban ambulatory centre,"Aim: To review the clinical experience for adult patients with Wilson's disease (WD) followed in an urban ambulatory setting. Methods: A retrospective review of patients with a diagnosis of WD was performed. Results: 59 charts were identified; based on Leipzig scores, 44 met criteria for likely (score >= 4) and 10 for probable WD (score 2-3). On review, 6 cases were excluded (1 likely, 5 probable). Presentation characteristics of the 48 patients included are shown in Table 1. At review, median time on treatment was 11.5 years (range 0.1-42 years). D-penicillamine (DP) was the most common initial therapy (48%), followed by zinc (23%), trientine (15%), DP and zinc (6%), and 8% unknown (initiated on treatment as part of a double blinded study). At review, zinc was the most common regimen (65%), followed by DP (17%), trientine (12%), and dual-therapy (6%). Side effects were most notable for DP (41%) compared to zinc (19%) or trientine (10%). Overall, liver biopsy and/or imaging demonstrated presence of portal hypertension in 63% and cirrhosis in 53% of patients. Liver biopsy (n=31) also identified fibrosis in 94% of patients, inflammatory activity in 68% and steatosis in 65%. Where evaluated, 10 patients had EM mitochondrial changes, and 13 glycogenated nuclei. Median liver copper concentration was 4.11muM/g (range 0.22-20.43). During follow up, 3 patients developed hepatic encephalopathy and 2 became jaundiced. 2 patients developed ascites (one of whom was initially asymptomatic) and 1 variceal bleed was documented. At time of review, there was one death and one transplant. Neurological WD patients (n=21) presented with a median of 4 neurological signs consistent with WD. At review, 14 patients had fewer neurological signs, 2 the same number, 4 more signs (1 patient lost to followup). Three patients with non-neurological presentation developed neurological signs, of which 1 recovered to baseline. Eleven patients had at least one episode of documented neurological decline while on treatment. Of patients who underwent an MRI (n=26), signal abnormalities were seen in the basal ganglia (62%), brainstem (50%), white matter tracts (38%), and thalamus (28%). Eight patients (31%) had normal brain MRI's. Of patients with a second MRI (n=11), 36% saw almost complete improvement. Conclusion: Wilson's disease is a diverse illness but outcomes are generally good over the long term for patients responding to initial therapy. (Table presented).",Wilson disease;liver disease;liver;adult;hospital;patient;nuclear magnetic resonance imaging;therapy;neurologic disease;follow up;liver biopsy;ascites;transplantation;basal ganglion;brain stem;death;thalamus;brain;general aspects of disease;diagnosis;side effect;imaging;portal hypertension;liver cirrhosis;fibrosis;steatosis;hepatic encephalopathy;white matter;zinc;trientine;penicillamine;copper,"Moores, A.;Fox, S.;Hirschfield, G. M.",2010,October,http://dx.doi.org/10.1002/hep.23979,0,1,
1846,Symptomatic Wilson disease during longterm zinc maintenance monotherapy after initial penicillamine decoppering: Experience in 30 patients,"Outcome of exclusive zinc monotherapy for symptomatic Wilson disease may be unfavourable, particularly in case of advanced hepatic disease (Hepatol 2009;50:1442-52). Initial decoppering with penicillamine might improve outcome, but available data are scarce and long-term follow up is not available. We here report our experience with such approach in 30 symptomatic pts during (median) 29 (range 0.5-48) yrs follow up (FU). Presentation was exclusive hepatic, exclusive neurologic or combined in 14, 3 and 13 cases resp. Mean age at diagnosis was 14 (range 7-37) yrs. Duration and dose of initial penicillamine were 2 (0.5-21) yrs and 873 (162-2000) mg resp. and of subsequent zinc 23 (0.5-42) yrs and 175 (68-279) mg resp. Of the 27 pts with hepatic or combined presentation, 3 exhibited initial decompensated cirrhosis, 11 compensated cirrhosis and 13 less severe disease. Of the 3 pts with initial decompensated cirrhosis, one improved to compensated cirrhosis and remains so during 23 yrs FU, 1 was transplanted after after 0.5 yr, and one initially improved but died 12 yrs later from complications of cirrhosis. Of the 11 pts with initial compensated cirrhosis (median FU 31 yrs), 1died after 2 yrs from penicillamine-induced myelinolysis, 3 died from complications of liver disease after 17, 20 and 30 yrs therapy and 7 remain stable after median 29 yrs FU. Of 13 pts with less severe hepatic disease, 9 deteriorated, including 5 to compensated and 1 to decompensated cirrhosis (the latter recompensating after trientine addition). Progressive hepatic disease was associated with longer follow up (median 31 vs 26 yrs, P=0.03) but could not be clearly explained by dose or duration of therapy or efficiency of decoppering (based on 24-hr urine copper excretion and serum non-ceruloplasmin bound copper conc. at end of FU). Of the 16 pts with initial neurologic or combined presentation, neurologic symptoms improved in 7, remain stable in 4, and deteriorated in 5 (including 1 with subsequent death from pneumonia). 3 pts with exclusive hepatic presentation developed neurologic symptoms and one pt with exclusive neurologic presentation developed hepatic disease during follow up. Major side effects occurred exclusively during penicillamine: glomerulonefritis (n=2) and death from myelinolysis (n=1). In conclusion, although short term clinical outcome is often satisfactory, hepatic Wilson disease tends to progress during long term zinc monotherapy, even after initial penicillamine decoppering.",patient;liver disease;Wilson disease;monotherapy;liver;liver cirrhosis;follow up;decompensated liver cirrhosis;neurologic disease;death;treatment duration;urine;serum;excretion;pneumonia;side effect;diagnosis;therapy;penicillamine;zinc;copper;trientine;ceruloplasmin,"Ras, J.;Houwen, R.;Linn, F. H.;Van Erpecum, K. J.",2010,October,http://dx.doi.org/10.1002/hep.23979,0,1,
1847,Therapeutic plasma exchange as a bridge to liver transplant in a pediatric patient with Wilson's disease,"Purpose: Wilson's disease (WD) is an autosomal-recessive disorder of impaired copper metabolism with a resultant accumulation of copper primarily in the liver, but ultimately in many organs and tissues. A small number of patients with WD initially present with fulminant hepatic failure, hypercupremia, and intravascular hemolysis. The therapeutic goals for these patients include quickly removing the copper via hemodialysis, peritoneal dialysis, or therapeutic plasma exchange (TPE) and preparing the patient for orthotopic liver transplantation (OLT). Here we report on a pediatric patient treated with TPE as a bridge to OLT. Case Report: The patient was a 6 year-old male with WD who presented in fulminant hepatic failure. He had been recently diagnosed based on a urinary copper excretion of 1480 lg/day and was receiving trientine as chelation therapy. The patient was jaundiced with elevated liver function tests, coagulopathy, and a moderate direct antiglobulin test-negative anemia. TPE was initiated as a means of stabilization until an OLT was possible. A total of 5 single volume (1500 mL) TPE were performed over the course of eleven days using the Cobe Spectra cell separator (CaridianBCT, Lakewood, CO) with fresh frozen plasma as the replacement fluid. Due to transfusion and chelation therapy, urine and serum copper levels were unreliable markers of copper stores. Additionally, the patient, who has a diagnosis of autism, had an unexpected temporary improvement in mental status after the first TPE. OLT was performed 15 days after his most recent admission and 12 days after beginning TPE. The post transplant course was uneventful. Currently 5 months post-transplant, the patient remains on chelation therapy and is doing well. Conclusions: TPE was a successful adjunctive therapy to bridge this patient with WD and fulminant hepatic failure to OLT. Clinical trials to investigate the role of TPE in WD are needed to further determine if this therapy should be broadly implemented.",patient;plasmapheresis;society;apheresis;Wilson disease;liver graft;chelation therapy;liver failure;therapy;transplantation;liquid;transfusion;copper blood level;diagnosis;autism;mental health;clinical trial;urine;autosomal recessive disorder;copper metabolism;liver;tissue;intravascular hemolysis;peritoneal dialysis;liver transplantation;case report;male;excretion;liver function test;blood clotting disorder;Coombs test;anemia;hemodialysis;copper;marker;trientine;fresh frozen plasma,"Morgan, S. M.;Zantek, N. D.",2010,,http://dx.doi.org/10.1002/jca.20230,0,0,
1848,Novel dermatological manifestations of Mowat-Wilson syndrome including photosensitivity and dyspigmentation,"The authors update on a previously reported patient with Mowat-Wilson syndrome (MWS) with unusual dermatological features including photosensitivity and skin dyspigmentation.<sup>1</sup> An 18-month-old Afro-Caribbean boy with Hirschsprung's disease, hypospadias, delayed visual maturation, microcephaly, developmental delay, seizures and dysmorphic facial features was referred to the dermatology department. Since birth he displayed persistent skin dyspigmentation with patchy macular hypo-and hyperpigmentation involving the face and neck, upper limbs, trunk, perineum and right ankle. There was no history of preceding inflammation or eczema. Following the original report, his parents have described photosensitivity since the age of 2 years, with sunburn-like erythema occurring within minutes of sun exposure despite application of high-factor sunblock. Investigations including lupus serology and porphyria screen were normal. The patient is currently awaiting formal phototesting. Genetic analysis previously identified a heterozygous truncating mutation in exon 8 of the ZEB2 (formerly ZFHXIB; Zinc finger homeobox 1B) gene, confirming MWS. MWS was first described in 1998, comprising characteristic facial dysmorphism, profound learning difficulties, epilepsy, Hirschprung's disease and other congenital abnormalities, mapped to a locus at chromosome 2q21-q23.<sup>2</sup> In 2001 the causative gene, ZEB2 was identified.<sup>3</sup> Subsequently, over 100 pathogenetic heterozygous mutations or deletions are described.<sup>4</sup> The distinctive evolving facial ZEB2 encodes Smad interacting protein (SIP1), a ubiquitous transcription factor with an important role in embryological development including the neural crest. ""Raindrop"" pigmentation has been previously reported in a 9-year-old patient with MWS.<sup>6</sup> This indicates that MWS should be added to the spectrum of neurocutaneous disorders comprising dyspigmentation and Hirschprung's. We can speculate that dyspigmentation results from ZEB2 haploinsufficiency disrupting neural crest melanocyte development or migration. Our case is the first record of photosensitivity in MWS, raising the possibility of an additional role of ZEB2 in regulating the cutaneous response to ultraviolet radiation.",photosensitivity;Wilson disease;pediatrics;child health;college;patient;skin;neural crest;gene;mutation;perineum;ankle;inflammation;eczema;parent;sunburn;erythema;sun exposure;serology;porphyria;genetic analysis;African Caribbean;exon;homeobox;learning disorder;epilepsy;congenital disorder;chromosome 2;pigmentation;phakomatosis;melanocyte;ultraviolet radiation;boy;hypospadias;maturation;microcephaly;seizure;facies;dermatology;hyperpigmentation;neck;arm;Hirschsprung disease;zinc finger protein;transcription factor;protein A,"Kaur, B.;Taibjee, S.;Abdullah, A.;Shannon, N.",2010,April,http://dx.doi.org/10.1136/adc.2010.186338.36,0,0,
1849,Efficacy and tolerance of zinc in the treatment of wilson disease,"Objectives and Study: To evaluate the efficacy and tolerance of zinc acetate in the treatment of Wilson's Disease (WD) in children. Methods: Twenty six WD patients treated with zinc acetate were included in this multicenter study. Clinical and biological data were collected via a questionnaire: age and symptoms at diagnosis of WD, age at beginning of zinc therapy, efficacy on biological parameters, side effects. Results: At presentation, 23 patients (88%) were asymptomatic, mostly diagnosed during a familial work-up; 23 patients (88%) had liver disease, and one (4%) had neurological symptoms. A Kayser-Fleischer ring was present in 15% of cases. Diagnosis of WD was made at a median age of 8 years (0.8 - 16.1). According to the centre, the percentage of WD patients treated with zinc varied from 8.5 to 61.5%. D-penicillamin was associated in 18 patients (69%), trientine in 4 (15%), and 3 patients (11%) received the 3 drugs. Zinc therapy was initiated at the time of diagnosis in 12 patients (46%), as the only drug in 8 cases. Median age at the beginning of zinc therapy was 10.8 years (2.3-12.3) and 2.6 years after the diagnosis of WD. In children who received only zinc, it was started at the age of 7 years (2.3 - 11.1), 5 months after the diagnosis of WD. Zinc was started at the recommended dosage in 11 children and progressively increased in 15 patients. A dosage above the recommended doses was used in 5/6 patients under 5 years of age, 10/19 in patients between 6 and 15 years, and 1/1 patient above 16 years. After the beginning of the treatment, the median ALT and urine copper values normalized in 5 months. Thereafter, urine copper values remained under 50mg/24 h in all patients but one patient with a poor compliance. Epigastralgia (n = 4), vomiting and diarrhea (n = 1), leucopenia (n = 1) and transient increase of serum lipase (n = 1) were observed. Conclusion: Although rarely used in the treatment of WD, zinc acetate effective and well tolerated. The guidelines regarding the dosage and the monitoring should be more closely followed.",nutrition;gastroenterology;society;Wilson disease;patient;diagnosis;child;therapy;urine;recommended drug dose;epigastric pain;vomiting;diarrhea;leukopenia;triacylglycerol lipase blood level;monitoring;multicenter study;questionnaire;side effect;liver disease;neurologic disease;zinc;zinc acetate;copper;trientine;penicillamine,"Lapeyre, D.;Gottrand, F.;Debray, D.;Bridoux-Henno, L.;Lachaux, A.;Morali, A.;Lamireau, T.",2010,June,http://dx.doi.org/10.1097/01.mpg.0000383075.98243.67,0,1,
1850,Wilson's disease in children: Monocentric experience with analysis of 114 children over a 18 years period,"Objectives and Study: Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism with a highly variable spectrum of clinical manifestations in childhood. We evaluated the clinical and laboratory characteristics of 114 children with WD to determine clinical presentation, diagnostic course and outcome. Methods: The medical reports of 114 children (63 boys) whom were diagnosed as WD between 1991 and 2009 were reviewed retrospectively. Physical examination, laboratory tests and liver biopsies of patients were evaluated. Results: The mean age at diagnosis was 9.5+/- 3.2 years (1.5-16 years. There was consanguity in majority of the parents (81, 71.1%. Eighty seven (76.3%) patients were diagnosed as symptomatic cases including 12 patients whom presented with acute liver failure. Twenty seven patients were diagnosed by family screening. Overall 80 patients presented with hepatic, 5 with neurologic, and 17 both hepatic and neurologic features. Hepatomegaly was the most common clinical finding, in 41 patients, while splenomegaly, icterus and ascites were found in 26, 25 and 24 patients respectively. Kayser-Fleischer rings were present in 63 of 109 patients (57.8%) while serum ceruloplasmin level was below 20 mg/dl in 97 of evaluated 114 patients (85.1%). Urinary copper excretion was above 80mg/24 hours in 85 of 102 patients (83.3%). Liver copper above (250mg/g dry weight) was found in 53 (67.0%) of 79 patients. Cirrhosis and chronic hepatitis were the most common findings of liver biopsy (23/79, 29.1% for each). All the patients with acute liver failure died except one who had liver transplantation. Ninety seven non-fulminant WD patients were treated with D-penicillamine and zinc sulphate, 5 with trientine and zinc sulphate at diagnosis. A total of 6 children were converted to trientine due to adverse reactions of penicillamine (nephrotic syndrome in 2, detoriation of liver functions in 2, Stevens-Johnson reaction in 1, allergic rash in 1 patient). Five patients had liver transplantation during follow-up. Seventy six non-fulminant WD patients had been followed up for 5.0+/- 3.7 years (3 months-14 years). Five patients died during the follow-up because of end stage liver disease. Eighteen patients who were nonadherent to chelation therapy had poor outcome. Conclusion: Wilson's disease in children may present in different forms and needs extensive investigation for diagnosis. Drug treatment is helpful for a stable or improved course of non-fulminant disease. Fulminant WD is almost mortal without liver transplantation.",child;nutrition;gastroenterology;society;patient;diagnosis;liver transplantation;liver biopsy;follow up;liver failure;laboratory test;parent;screening;hepatomegaly;splenomegaly;jaundice;ascites;ceruloplasmin blood level;liver;dry weight;liver cirrhosis;excretion;Wilson disease;chronic hepatitis;adverse drug reaction;nephrotic syndrome;liver function;allergic rash;chelation therapy;drug therapy;autosomal recessive disorder;copper metabolism;childhood;laboratory;boy;physical examination;liver disease;penicillamine;trientine;zinc sulfate;copper,"Yuce, A.;Uslu, N.;Balamtekin, N.;Demir, H.;Saltik Temizel, I.;Baysoy, G.;Usta, Y.;H, O. zen;Gurakan, F.",2010,June,http://dx.doi.org/10.1097/01.mpg.0000383075.98243.67,0,1,
1851,Re-evaluation of the diagnostic criteria for wilson's disease in children with mild liver disease,"Objectives and Study: Wilson's disease (WD) is a challenging diagnosis, especially in children. Early diagnosis is desirable in order to avoid disease progression. Aim of our study was to re-evaluate the conventional diagnostic criteria and Ferenci's diagnostic score (1) in WD children with mild liver disease. Methods: We retrospectively evaluated 43 consecutive children with WD (28 boys, age range: 1.1-20.9 years) and 58 age- and sex-matched patients with liver disease other than WD. Both groups were symptom-free with hypertransaminasemia as prevalent sign of liver disease. In all WD patients diagnosis was confirmed by molecular analysis and/ or liver copper content. Results: ROC analysis for ceruloplasmin at cut-off of <20 mg/dl showed sensitivity of 95.4% (95% CIs, 84.5-99.4%) and specificity of 84.4% (95% CIs, 72.5-92.6%). Optimal basal urinary copper diagnostic cut-off was found to be >40 mcg/24 h (sensitivity of 78% [95% CIs, 62.4-89.4%] and specificity 87.9% [95% CI, 76.7-95%]). Urinary copper after penicillamine challenge had 15.4% sensitivity only. Liver copper >250mcg/g dry weight had 96.7% sensitivity [95% CIs, 82.8-99.9%] and 95.8% specificity [95% CIs, 78.9-99.9%]). Ferenci's diagnostic score showed 93% positive and 91.6% negative predictive value, respectively. Conclusion: Urinary copper excretion is suggestive of WD when above 40 mcg/24 h, rather than 100 mcg/24 h, as suggested by recent AASLD guidelines (2). Instead, penicillamine challenge test should not be performed in asymptomatic patients. Ferenci's diagnostic score shows good diagnostic accuracy. Diagnosis ofWDrequires multiple tests and high index of suspicion.(Table presented).",diagnosis;society;liver disease;child;gastroenterology;Wilson disease;nutrition;patient;liver;early diagnosis;receiver operating characteristic;boy;dry weight;excretion;provocation test;diagnostic accuracy;disease course;hypertransaminasemia;copper;penicillamine;ceruloplasmin,"Ranucci, G.;Nicastro, E.;Vajro, P.;Vegnente, A.;Iorio, R.",2010,June,http://dx.doi.org/10.1097/01.mpg.0000383075.98243.67,0,0,
1852,Extracorporeal liver support therapy,"INTRODUCTION. Extracorporeal liver support therapy is in its infancy but is valued as a detoxification treatment option for patients with cirrhosis who have rapid worsening of their liver function. We report the use of Prometheus, a new extracorporeal liver support system allowing the removal of protein bound and water soluble toxins by fractionated plasma separation and absorption (FPSA) in a patient with Wilson's disease (WD) who developed rapid worsening of their liver function. METHODS. A 26-year-old female patient, diagnosed with WD since the age of 17, was initially treated in an irregular pattern with penicillamine. Therapy was discontinued. Now, 2 years later, she developed acute decompensated liver failure with hepatic encephalopathy with a MELD 29. Liver transplantation (LT) was the treatment option for this patient. But, in this case, the rapid and adverse evolution of the liver failure with renal failure and the unknown waiting time for a emergency liver donor in our country led us to use the Extracorporeal liver support therapy. RESULTS. After 5 h 30 min of therapy we reduced the amount of bilirrubin for less than a half, we increase the urinary output and next day the patient went to liver transplant, stable, with a renal function improved. CONCLUSIONS. Acute liver failure due to WD is most of the time fatal without emergency LT. This case report highlights discontinuation of chelants treatment in a patient with WD. As the patient progressed to decompensated liver cirrhosis with encephalopathy, LT was the only treatment option but while we don't get a donnor, we can use, for a short period of time, an Extracorporeal liver support therapy as a very useful bridge. Results from two studies presented at the recent EASL 2010 Congress have shown that treatment with extracorporeal devices may not confer a survival advantage for severe liver failure patients, despite positive dialysis effects. However, results among a small sub-group of patients show promise like severely ill patients with hepatorenal syndrome type 1 or a MELD score over 30.",therapy;liver support;intensive care;society;patient;liver failure;liver function;emergency;kidney failure;liver;donor;urine volume;liver graft;kidney function;case report;decompensated liver cirrhosis;brain disease;device;survival;dialysis;hepatorenal syndrome;infancy;detoxification;liver cirrhosis;Wilson disease;plasma;absorption;female;hepatic encephalopathy;liver transplantation;water;toxin;penicillamine;protein,"Marinho, A. D.;Pais, T. P.;Pessegueiro, H.;Daniel, J.;Rua, F.",2010,September,http://dx.doi.org/10.1007/s00134-010-2001-7,0,0,
1853,"Anesthetic management of a pediatric patient with wilsons disease, is spinal anesthesia safe-a case report","Wilsons disease, characterized by cirrhosis, extrapyramidal symptoms and Kayser-Fleischer corneal rings, is a rare hereditary disease of human copper metabolism. Wilsons Disease involves loss of the ability to export copper from the liver into bile and to incorporate copper into hepatic ceruloplasmin. Accumulation of copper in various organs and tissues occurs, especially in the liver, brain, kidneys, and cornea Clinical findings in Wilsons disease are complex and neurological symptoms such as tremor, dysarthria, rigid dystonia, seizures, psychiatric disorders, acute liver failure, chronic hepatitis or cirrhosis may develop. A 6-year-old female patient was operated for contractures at the hip joint. she was diagnosed with Wilsons disease at the age of 2.5 years and treated with zinc sulphate and D-penicillamine. Spinal anesthesia with bupivacaine 0.5% was given at L3-L4 level .This patient was sedated with midazolam for providing the Spinal anesthesia. No complications were encountered during the operation or in the postoperative period. We concluded that Spinal anesthesia can successfully be given to Wilson's disease patients and spinal anesthesia is preferred to general anesthesia as most of the anesthetic agents are metabolized by liver and may aggravate hepatic tox-icity, By close follow-up of patients clinically and biochemically, it is possible to reduce the complication rates to a minimum.",patient;spinal anesthesia;case report;society;regional anesthesia;liver;liver cirrhosis;seizure;mental disease;liver failure;chronic hepatitis;dysarthria;female;contracture;hip;postoperative period;general anesthesia;follow up;extrapyramidal symptom;genetic disorder;human;Wilson disease;bile;tissue;brain;kidney;cornea;neurologic disease;tremor;dystonia;copper metabolism;anesthetic agent;copper;zinc sulfate;penicillamine;midazolam;bupivacaine;ceruloplasmin,"Pradeep Kumar, K.;Padmaja, K.;Subramanyam, G.;Muralidhar Rao, J.;Kishore, K.;Srinivas, P.;Jagadesh, G.",2010,September-October,http://dx.doi.org/10.1097/AAP.0b013e3181f3582c,0,0,
1854,Elevated plasma copper/zinc ratios in patients with schizophrenia,"Introduction: Copper and zinc are neuroactive substances that can be synaptically released during neuronal activity. These metals have been implicated in diseases with neuropsycho- pathological components, including Alzheimer's disease, Menkes disease, Wilson's disease, Pick's disease, stroke, seizures and schizophrenia. The purpose of the present study was to examine the plasma levels of copper (Cu) and zinc (Zn) in schizophrenic patients and to compare the Cu/Zn ratios with that of matched healthy subjects. Materials and methods: 40 patients with schizophrenia were sampled (35 males and 5 females; mean age 32.77 years) along with 50 (41 males and 9 females; mean age 31.44 years) healthy controls. Exclusion criteria included another concurrent psychiatric disorder, pregnancy, and medical disorders or drugs known to affect trace element metabolism. Fasting blood samples were withdrawn from an antecubital vein between 07.00 and 09.00 h. Plasma copper and zinc levels were measured using an atomic absorption spectrophotometer. Two-tailed t-test was used to determine statistical differences. Differences were considered significant at the level of p<0.05. Results:Mean Cu or Zn levels and Cu/Zn ratios for each of the two groups are shown below: Cu (mug/dl) =65+/-3 or 145+/-28, control or patients, respectively, p<0.005. Zn (mug/dl)=81+/-4 or 67+/-2, control or patients, respectively, p<0.05. Cu/Zn ratio=0.87+/-0.04 or 2.07+/-0.38, control or patients, respectively, p<0.05. Conclusion: There was a significant higher Cu/Zn ratio in schizophrenic patients compared to healthy subjects. These results suggest that Cu and Zn may be involved in the pathophysiology of schizophrenia.",patient;schizophrenia;health care organization;plasma;male;female;normal human;blood sampling;vein;atomic absorption;spectrophotometer;Student t test;copper blood level;pathophysiology;Alzheimer disease;Wilson disease;Menkes syndrome;stroke;seizure;blood level;mental disease;pregnancy;metabolism;diet restriction;Pick presenile dementia;zinc;copper;metal;trace element,"Mansouri, N.;Farzin, D.",2010,September,http://dx.doi.org/10.1111/j.1468-1331.2010.03233.x,0,0,
1855,Gait disorder in a patient with Wilson's disease 18 years after onset of disease,"Objective: Wilson's disease is an autosomal recessive inherited disorder of copper metabolism leading to an excessive accumulation of copper in and outside the liver. A broad spectrum of neurological symptoms comprising dystonia, parkinsonian features, cerebellar and bulbar signs is very common and can severely impact the patient's quality of life. Even though gait disorder is a quite prominent neurological sign in Wilson's disease, the features of the gait abnormalities have not been described in detail in the literature. We describe the gait abnormalities in a patient who has been suffering from clinical signs of Wilson's disease for 18 years and has been treated with different anticopper agents since the first diagnosis in 1992. Methods: This 51-year-old male patient was diagnosed with Wilson's disease at the age of 33 after a 2 years lasting history of severe arm and head tremor resulting in a significant impairment of his working ability. Irritable and aggressive behavior was present at time of disease onset and worsened in the first years after the diagnosis. He reported a marked progression of symptoms after changing the treatment from D-penicillamin to zinc sulfate in the late 1990s. Even though D-penicillamine was reintroduced, since this time walking remained impaired and the patient has been bound to a walking frame to overcome his gait disorder in a suitable manner. Recent urine analysis showed that copper was effectively eliminated under D-penicillamine. Results: On the neurological examination the patient revealed a complex gait disorder comprising features of severe (gait-specific) dystonia, gait apraxia and freezing of gait (FOG), respectively. While walking sidewards along the wall he used a simple cue to improve his gait impairment. Otherwise no significant impairment of leg motility or marked dystonic features could be observed when he was in a sitting or lying position. Some frontal signs were positive in this patient, pyramidal signs, however, were missing. Conclusion: This is an illustrative case showing a particular pattern of gait abnormalities with a combination of FOG and dystonia. While dystonia is well known in patients with Wilson's disease FOG is unusual and could reflect the involvement of different neuroanatomical structures beyond the basal ganglia pathology.",patient;Wilson disease;gait disorder;society;gait;dystonia;walking;neurologic disease;diagnosis;male;arm;tremor;work capacity;aggression;urinalysis;neurologic examination;freezing;leg;sitting;recumbency;pyramidal sign;basal ganglion;pathology;autosomal recessive inheritance;copper metabolism;liver;bulbar paralysis;quality of life;apraxia;penicillamine;copper;zinc sulfate,"Brugger, F.;Felbecker, A.;Kagi, G.;Hagele-Link, S.;Tettenborn, B.",2010,June,http://dx.doi.org/10.1007/s00415-010-5575-7,0,0,
1856,Persistence with anti-copper treatment among patients with Wilson disease,"Objective: Wilson disease is genetically determined failure of copper metabolism. If untreated, it usually leads to death within several years from the development of clinical symptoms. Drugs which deplete copper should be continued over the whole span of patient's life after diagnosis. Clinical observations show that patients with Wilson disease frequently stop the treatment. The aim of the study was to evaluate drug compliance (defined by us as persistence with treatment) among Wilson disease patients prescribed different anti-copper drugs, and to assess how it translates into clinical improvement and the total well-being. Methods: Our study was based on a retrospective analysis of information received from self-completion questionnaires given to patients attending Wilson disease clinic. The following data were obtained from each patient: prescribed medication, duration of treatment, persistence with treatment, subjective assessment of health status. EQ-5D questionnaire with visual analogue scale (VAS) of well-being was also used. Results: Response was obtained from 120 subjects, but only 104 questionnaires could be used for further processing. Fifty fife percent of patients were treated with d-penicillamine, and the rest were treated with zinc sulphate. The mean duration of treatment was 10.3 (SD +/- 4.4) years. Our analysis did not reveal differences in persistence with d-penicillamine or zinc sulphate treatment (75.0% vs. 73.0% respectively), nor in efficacy of above medications. We have discovered, however, that regardless of used medication, persistence with drug therapy resulted in significantly better results of selfassessment: ""total improvement"": 39.7% of vs. 7.7% in persistent vs. non-persistent group, respectively, p=0.003; ""partial improvement"": 53.8% vs. 30.8%, respectively, p=0.045; ""deterioration"": 0.0% vs. 42.3%, respectively, p<0.0001. Patients persistent with treatment obtained higher scores in VAS than non persistent (76 vs.67, p=0.05). Conclusion: Persistence with anti-copper treatment is a major factor influencing the long-term clinical outcome in Wilson disease.",patient;Wilson disease;society;drug therapy;questionnaire;treatment duration;wellbeing;copper metabolism;death;diagnosis;clinical observation;patient compliance;hospital;health status;visual analog scale;processing;deterioration;copper;penicillamine;zinc sulfate,"Czlonkowska, A.;Maselbas, W.;Chabik, G.;Czlonkowski, A.",2010,June,http://dx.doi.org/10.1007/s00415-010-5575-7,0,1,
1857,Complex neuropsychiatric symptoms in adolescent Wilson's disease: The need for multidisciplinary care,"Objective: To describe the case of a young adult with Wilson's disease (WD) with severe neuropsychiatric illness significantly impairing her quality of life. To advocate for early detection of these symptoms and multi-disciplinary care. Background: WD is an autosomal recessive disorder of copper transport and metabolism affecting 1 in 30000 people. Children and young adults predominantly present to paediatric services due to hepatic dysfunction. A large number of these patients will have unrecognized and unreported co-morbid neuropsychiatric symptoms. Our centre has developed a multidisciplinary team for the management of WD. This is one case highlighting the importance of this approach. Methods: Description of the case history, MR imaging, course of treatment and clinical outcome. Results: A 19 year-old female with a 9 year history of genetically-proven WD treated with penicillamine was seen in our multidisciplinary WD clinic. Although she had stable liver disease on penicillamine, direct questioning revealed a significant two year history of social anxiety and low mood. Psychiatric evaluation detected paranoia. She had a mild tremor. Worsening depression led to hospital admission for psychiatric symptoms and antidepressant therapy with venlafaxine was commenced. During her inpatient stay, she developed parkinsonism and was started on levo-dopa. This has improved her movement disorder but she continues to require intense psychiatric support. A multidisciplinary WD team, including hepatologists, neurologists and psychiatrists, has allowed for detection, appropriate diagnosis and prompt management of the patient's marked neuropsychiatric symptoms. Conclusions: Neuropsychiatric symptoms in children and young adults with WD are not rare. All clinician's who manage children or young people presenting with liver disease and diagnosed with WD need to screen for neuropsychiatric symptoms at diagnosis and during the ongoing management. Using a multidisciplinary approach, we are more able to identify previously undiagnosed co-morbidity requiring urgent intervention.",Wilson disease;Parkinson disease;adolescent;motor dysfunction;child;adult;diagnosis;liver disease;patient;hospital patient;parkinsonism;psychiatrist;morbidity;quality of life;general aspects of disease;autosomal recessive disorder;liver dysfunction;metabolism;female;anxiety;nuclear magnetic resonance imaging;mood;paranoia;tremor;hospital admission;mental disease;therapy;hospital;penicillamine;levodopa;copper;antidepressant agent;venlafaxine,"Hedderly, T.;Hinnell, C.;Moriarty, J.;Jarosz, J.;Hindley, P.;Dhawan, A.;Sherwood, R.;Samuel, M.",2010,,http://dx.doi.org/10.1002/mds.23162,0,0,
1858,A retrospective study about characteristics of Wilson's disease at tertiary care institute of North India,"Objective: To study the clinical profiles, laboratory findings, brain imaging of Wilson's disease and response to treatments. Background: Wilson's disease is an autosomal recessive systemic disorder of copper metabolism due to a defect of copper transport by hepatic lysosomes with secondary pathology resulting from copper overload in liver, brain, kidney and skeletal system. Methods: Cases of Wilson's disease were taken from hospital records from 2004 December to 2009 December. Total 32 cases were diagnosed. Study was carried out to see clinical characteristics, presence of K-F ring, laboratory parameters, biochemical levels and brain imaging. Results: Total 32 cases were diagnosed of Wilson's disease. 22 were male and 10 were female. 28 cases were of less than 15 years of age and 4 were adults. Youngest patient was of 6.5 years of age and oldest patient was of 32 years of age at diagnosis. The mean duration of disease before diagnosis was 6 months in children (<15 yrs) and 2 years in adult (>15 years). In children dystonia was most commonest presentation (90%), parkinsonism (82.5%), both were in 73.4% and tremor in 60% and in adults parkinsonism was commonest presentation (75%), dystonia (50%) and tremor were present in 50% of adult patient. Sialorrhoea was present in 60% of children and 25% of adult patients. Unclear voice were present in 80% of cases. Dysphagia was present in 44% of children and 25% of adult patients. KF ring was absent in 3 children. CT brain was performed in all the cases, most common abnormality observed is bilateral symmetrical hyperlucency of basal ganglia in 13 (40.6%). MRI brain performed in 24 cases. 4 had normal MRI brain. Abnormality were observed in 20 cases, most common was hyperintensities of basal ganglia (62.5%), thalamus in 45% and brainstem in 31.5%. 4 patients were only on zinc and 28 were on both zinc and D-penicillamine. Out of 28 cases 10 has left D-penicillamine (2 due to adverse effects and 8 due to unaffordability). All has excellent response to treatment except one child. Conclusions: Wilson's disease was more common in children. Dystonia, parkinsonism, tremor, sialorrhoea and unclear voice were commonest features. KF ring were present in 91% of cases. Bilateral symmetrical hyperintensities of basal ganglia was commonest MRI abnormality. Zinc is safest to start. Wilson's disease has excellent response to D-penicillamine.",Wilson disease;tertiary health care;India;Parkinson disease;retrospective study;motor dysfunction;child;adult;patient;brain;dystonia;parkinsonism;tremor;basal ganglion;nuclear magnetic resonance imaging;imaging;diagnosis;voice;hypersalivation;laboratory;thalamus;brain stem;copper metabolism;medical record;male;female;systemic disease;autosomal recessive inheritance;dysphagia;skeleton;adverse drug reaction;liver lysosome;pathology;liver;kidney;penicillamine;zinc;copper,"Kumar, A.;Kumar, R.;Kumar, U.;Sharan, A.;Shahi, S. K.",2010,,http://dx.doi.org/10.1002/mds.23162,0,1,
1859,Successful treatment of Wilson's disease dystonia with botulinum toxin,"Objective: To report a case of WD dystonia which was successfully treated with botulinum toxin A (BTA) injections. Background: Progressive hepatolenticular degeneration or Wilson's disease (WD) is an inherited disorder of copper metabolism caused by a mutation in the ATP7B gene. Neurological signs mainly include akinetic-rigid and dystonic syndromes, tremor and ataxia. Firstly described as a lethal neurological and hepatic familial disease, now it has different drug therapies. However, treatment of the WD with neurological symptoms is currently a challenge issue. Methods: A 38-year-old woman was diagnosed of WD in 1985. She was initially treated with penicillamine which was changed to trientine in 1988 because of lupus-like syndrome. In 2007 she developed a progressive parkinsonian syndrome and dystonia that required ammonium tetrathiomolybdate and zinc therapy. She improved clinically but due to persistent bilateral leg dystonia we tried botulinum toxin, with a dose of 1000 U BTA (Dysport) in the bilateral extensor hallucis longus, flexor hallucis brevis, abductor hallucis and abductor digiti quinti muscles with EMG guidance. Results: Two weeks later, she noted a functional improvement allowing footwear to be worn comfortably and a reduction in symptoms, with decreased spasm, pain relief and improvement of contractures. Two additional injections of 500 U BTA were given at fourmonthly intervals with good effect. No adverse event was reported. She is now neurologically stable. Conclusions: BTA injections in the involved muscles should be considered as a treatment option in WD dystonia management that can be followed by marked functional improvement and reduction of systemic drugs. In our patient, significant improvement started 2 weeks after the injections and lasted about 4 months.",Parkinson disease;dystonia;Wilson disease;motor dysfunction;injection;neurologic disease;muscle;muscle spasm;analgesia;contracture;patient;copper metabolism;mutation;gene;tremor;familial disease;drug therapy;electromyogram;lupus like syndrome;parkinsonism;therapy;leg;shoe;female;botulinum toxin;botulinum toxin A;trientine;tetrathiomolybdate ammonium;zinc;penicillamine,"De Fabregues, O.;Palasi, A.;Callen, A.;Hernandez-Vara, J.;Alvarez-Sabin, J.",2010,,http://dx.doi.org/10.1002/mds.23162,0,0,
1860,Treatment of Wilson's disease with ammonium tetrathiomolybdate: Experience in 3 cases with neurological symptoms,"Objective: To report our experience with TTMo in WD. Background: Wilson's disease (WD) is an inherited disorder of copper metabolism caused by a mutation in the ATP7B gene. Firstly described as a lethal neurological and hepatic familial disease, now it has different drug therapies. However, neurologic deterioration and severe adverse reactions have been reported with penicillamine and trientine which require the use of other drugs such as ammonium tetrathiomolybdate (TTMo). Methods: These 3 patients with WD with neurologic impairment were treated with TTMo 120 mg/day for 8 weeks. All patients were clinically assessed with the UWDRS neurological subscale and GAS for WD, video and neuroimage, before and 6 months after treatment. Drug adverse events were evaluated by hematologic and biochemical measures and clinical follow-up. Results: Different reasons for TTMo treatment: neurological deterioration with penicillamine, intolerance to conventional treatment and neurologic presentation of WD. Effectiveness: no patients had neurological deterioration. All patients had clinical improvement with UWDRS average drop of 34 points (improvement of 64%) and 14 points GAS for WD (47% improvement). Well tolerated in 2 cases, treatment lasted 8 weeks more in 1 case, 1 case had elevated transaminases that cause dose reduction and transient suppression. Improved neuroimaging in 2 cases. Subsequent clinical evolution: moderate neurological sequelae 2 and mild 1 case, 1 death unrelated to treatment. Conclusions: Treatment of the WD with neurological symptoms is a challenge issue. Concern is made on penicillamine and trientine as first line treatment election. TTMo is an effective well tolerated therapeutic alternative even though its contraindications need to be clarified.",Parkinson disease;Wilson disease;neurologic disease;motor dysfunction;patient;deterioration;drug therapy;adverse drug reaction;hypertransaminasemia;drug dose reduction;neuroimaging;death;election;follow up;copper metabolism;mutation;gene;familial disease;videorecording;tetrathiomolybdate ammonium;penicillamine;trientine,"De Fabregues, O.;Palasi, A.;Gamez, J.;Callen, A.;Hernandez-Vara, J.;Duero, M.;Auge, C.;Alvarez-Sabin, J.",2010,,http://dx.doi.org/10.1002/mds.23162,0,0,
1861,"Copper metabolism and inherited copper transport disorders: Molecular mechanisms, screening, and treatment","In this review, we discuss genetic disorders involving altered copper metabolism, particularly in relation to Menkes disease (MD), occipital horn syndrome (OHS), and Wilson's disease (WD). The responsible genes for MD and WD are ATP7A and ATP7B, respectively. Both proteins encoded by these genes are responsible for transporting copper from the cytosol to the Golgi apparatus. However, the pathology of MD is completely different from that of WD, that is, MD is characterized by a copper deficiency while WD is caused by a toxic excess of copper. The reason for this difference is related to the particular cell types in which the ATP7A and ATP7B proteins are expressed. ATP7A is expressed in almost all cell types except hepatocytes, whereas ATP7B is mainly expressed in hepatocytes. MD and OHS are X-linked recessive disorders characterized by copper deficiency. Typical features of MD, such as neurological disturbances, connective tissue disorders, and hair abnormalities, can be explained by the abnormally low activity of copper-dependent enzymes. The current standard-of-care treatment for MD is parenteral administrations of copper-histidine. When the treatment is initiated in newborn babies prior to two months of age, the neurological degeneration may be prevented, but delayed treatment is considerably less effective. Moreover, copper-histidine treatment does not improve symptoms of the connective tissue disorders. As such, systems for mass screening of neonates for MD should be implemented. At the same time, novel treatments targeting connective tissue disorders need to be developed. OHS is a milder form of MD and is characterized by connective tissue abnormalities. Although formal trials have not been conducted for OHS, OHS patients are typically treated in a similar manner to those with MD. WD is an autosomal recessive disorder characterized by the toxic effects of chronic exposure to high levels of copper. The hepatic and nervous systems are typically most severely affected. Numerous other symptoms can also be observed, however, making an early diagnosis difficult. Chelating agents and zinc are effective for the treatment of WD, but they are ineffective for the patients with fulminant hepatic failure. Some patients with neurological diseases show poor response to chelating agents; here again, early diagnosis and treatment are critical. Screening of newborn babies or infants for WD can help lead to timely diagnosis and treatment. Patients with WD may have a risk of hepatocellular carcinoma despite receiving treatment. An understanding of the relation between WD and hepatocellular carcinoma will provide clues to help prevent hepatocellular carcinoma in patients with WD. © The Royal Society of Chemistry 2009.",autosomal recessive disorder;cancer risk;connective tissue disease;copper deficiency;copper metabolism;disease association;early diagnosis;hair disease;human;liver cell;liver cell carcinoma;liver failure;Menkes syndrome/dt [Drug Therapy];Menkes syndrome/di [Diagnosis];metabolic disorder/di [Diagnosis];neurologic disease;newborn screening;nonhuman;occipital horn syndrome/di [Diagnosis];priority journal;protein expression;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];X chromosome recessive disorder;chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];histidine;histidine copper/dt [Drug Therapy];histidine copper/pa [Parenteral Drug Administration];Menkes protein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Kodama, H.;Fujisawa, C.",2009,January,http://dx.doi.org/10.1039/b816011m,0,0,
1862,Liver disease: Early signs you may be missing,,abdominal swelling;alanine aminotransferase blood level;alcohol abuse;alcohol consumption;ascites/co [Complication];ascites/di [Diagnosis];ascites/dt [Drug Therapy];aspartate aminotransferase blood level;autoimmune hepatitis/dt [Drug Therapy];bacterial peritonitis/co [Complication];bacterial peritonitis/dt [Drug Therapy];bacterial peritonitis/pc [Prevention];delta agent hepatitis/dt [Drug Therapy];diabetes mellitus/dt [Drug Therapy];echography;elastography;esophagus varices/co [Complication];fatigue;fatty liver;fever/co [Complication];fragility fracture;hemochromatosis/dt [Drug Therapy];hepatic encephalopathy/co [Complication];hepatitis/si [Side Effect];hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];home care;hospital care;human;hyperglycemia/dt [Drug Therapy];hyperglycemia/th [Therapy];laboratory test;liver biopsy;liver cirrhosis/di [Diagnosis];liver failure/si [Side Effect];liver fibrosis/di [Diagnosis];liver function;long term care;malnutrition;non insulin dependent diabetes mellitus/dt [Drug Therapy];nonalcoholic fatty liver/di [Diagnosis];nonalcoholic fatty liver/dt [Drug Therapy];nonalcoholic fatty liver/th [Therapy];obesity;osteoporosis/co [Complication];portal hypertension/co [Complication];primary biliary cirrhosis/dt [Drug Therapy];review;risk factor;sepsis/co [Complication];steatosis/si [Side Effect];virus hepatitis;Wilson disease/dt [Drug Therapy];adefovir/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alpha tocopherol/dt [Drug Therapy];alpha2b interferon/dt [Drug Therapy];amiodarone/ae [Adverse Drug Reaction];aspartate aminotransferase/ec [Endogenous Compound];azathioprine/dt [Drug Therapy];chelating agent/dt [Drug Therapy];entecavir/dt [Drug Therapy];furosemide/dt [Drug Therapy];glitazone derivative/dt [Drug Therapy];insulin/dt [Drug Therapy];insulin sensitizing agent/dt [Drug Therapy];interferon/cb [Drug Combination];interferon/dt [Drug Therapy];kava extract/ae [Adverse Drug Reaction];lamivudine/dt [Drug Therapy];metformin/dt [Drug Therapy];norfloxacin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];repaglinide/dt [Drug Therapy];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];silymarin/dt [Drug Therapy];spironolactone/dt [Drug Therapy];sulfonylurea derivative/dt [Drug Therapy];telbivudine/dt [Drug Therapy];tenofovir/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];valproic acid/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Ignazio, G.;Ubaldi, E.;Portincasa, P.;Palasciano, G.",2009,October,,0,0,
1863,Mimicry of acute cholecystitis from Wilson's disease,"We present a 33-year-old Chinese woman with Wilson's disease in whom ultrasonography and computed tomography showed gallbladder features suggestive of acute cholecystitis. Incongruence in liver function prompted further investigations with the final diagnosis of Wilson's disease, complicated by oedema of the gallbladder mimicking acute cholecystitis. The patient was subsequently treated nonoperatively, and is well on follow-up.",Cholecystitis;Gallbladder disease;Wilson's disease;acute cholecystitis;adult;article;case report;Chinese;computer assisted tomography;consanguinity;conservative treatment;differential diagnosis;echography;female;follow up;genetic screening;human;liver function test;magnetic resonance cholangiopancreatography;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Chang, S. K. Y.;Chan, C. L. M.;Yu, R. Q.;Wai, C. T.",2009,March,,0,0,
1864,Systematic review: Clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease,"Background No consensus is available on the optimal initial treatment in Wilson disease. Aim To assess systematically the available literature of treatment in newly presenting patients with a presymptomatic, hepatic or neurological presentation of Wilson disease. Methods A systematic literature search of the MEDLINE, EMBASE and COCHRANE databases was performed. Original studies on clinical efficacy of d-penicillamine, trientine, tetrathiomolybdate or zinc monotherapy as initial treatment in Wilson disease were included. A descriptive analysis of the relevant published data was performed. Results One randomized trial and 12 observational studies met the inclusion criteria. These studies were quite heterogeneous and generally of low validity. Nevertheless, according to currently available data, patients with hepatic presentation of Wilson disease are probably most effectively treated by d-penicillamine. Zinc seems to be preferred above d-penicillamine for treatment of presymptomatic and neurological patients, as in these subgroups, the tolerance profile is in favour of zinc, while no obvious differences in clinical efficacy could be observed. Conclusions There is lack of high-quality evidence to estimate the relative treatment effects of the available drugs in Wilson disease. Therefore, multicentre prospective randomized controlled comparative trials are necessary. © 2009 Blackwell Publishing Ltd.",article;clinical feature;clinical trial;drug efficacy;drug tolerance;drug withdrawal;gastrointestinal symptom/si [Side Effect];human;monotherapy;priority journal;systematic review;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/pc [Prevention];penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ct [Clinical Trial];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/ct [Clinical Trial];zinc/dt [Drug Therapy],"Wiggelinkhuizen, M.;Tilanus, M. E. C.;Bollen, C. W.;Houwen, R. H. J.",2009,May,http://dx.doi.org/10.1111/j.1365-2036.2009.03959.x,0,0,
1865,"The interpretation of ""Guidelines for diagnosis and treatment of hepatolenticular degeneration"". [Chinese]",,clinical protocol;disease classification;disease severity;food and drug administration;haplotype;human;liver failure;molecular biology;phenotype;practice guideline;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Liang, X. L.",2009,June,http://dx.doi.org/10.3969/j.issn.1672-6731.2009.03.003,0,0,
1866,Clinical improvement of a patient with severe Wilson's disease after a single session of therapeutic plasma exchange,"Here, we report a case of a 17-year old female with Wilson's disease presenting with progressive Coombs' negative hemolytic anemia and hepatic cirrhosis who was treated with one session of therapeutic plasma exchange (TPE) and clinically improved. In clinical situations where multiple sessions of TPE may not be possible, the use of a single session of TPE in conjunction with conventional therapy may be of benefit in preventing further clinical deterioration. © 2009 Wiley-Liss, Inc.",Cirrhosis;Hemolytic anemia;Therapeutic plasma exchange;Wilson's disease;adolescent;article;case report;clinical effectiveness;Coombs positive hemolytic anemia;disease duration;disease severity;female;human;liver cirrhosis;plasmapheresis;treatment duration;treatment response;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Hursitoglu, M.;Kara, O.;Cikrikcioglu, M. A.;Celepkulu, T.;Aydin, S.;Tukek, T.",2009,,http://dx.doi.org/10.1002/jca.20186,0,0,
1867,Penicillamine-induced elastosis of the mucosal lip,"Long-term penicillamine therapy has been associated with alterations in dermal elastic tissue. Well-described associated dermatoses include pseudo-pseudoxanthoma elasticum, acquired cutis laxa, elastosis perforans serpiginosa, and anetoderma. Histologically, ""lumpy-bumpy"""" or ""bramble-bush"""" morphologic changes of elastic fibers in the dermis are characteristic. Previous reports of these findings in normal-appearing skin and internal organs suggest a systemic elastolytic process. Here we report an unusual case of penicillamine-induced elastosis affecting the mucosa of the lip with characteristic histologic features. © 2008 American Academy of Dermatology, Inc.",add on therapy;adult;article;axilla;case report;copper blood level;drug substitution;drug withdrawal;elastosis/si [Side Effect];elastosis/di [Diagnosis];elastosis/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/dt [Drug Therapy];human;human tissue;lip;male;mucosa;physical examination;priority journal;punch biopsy;skin biopsy;treatment response;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tazarotene/dt [Drug Therapy];tazarotene/tp [Topical Drug Administration];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy],"Lewis, B. K. H.;Chern, P. L.;Stone, M. S.",2009,April,http://dx.doi.org/10.1016/j.jaad.2008.09.018,0,0,
1868,Pregnancy and Wilson disease. [Portuguese],"Wilson disease is an autosomal recessive inherited disorder, with an affected gene (ATP7B) located at chromosome 13. It has been shown to affect the copper transport leading to a hepatic accumulation and deposition in other organs, specially brains, kidneys and cornea. The worldwide prevalence of Wilson's disease is around 30 per million. Around 60-70% of all cases are diagnosed between the ages of 8 to 20 years old. Clinically the condition may present with hepatic, neurologic or psychiatric disease. The diagnosis is based on a high level of suspicion and on the combination of both clinical and laboratorial findings. The gold standard exam for Wilson's disease diagnosis is the liver biopsy with determination of hepatic copper levels. The treatment is lifelong pharmacological therapy or hepatic transplant. Currently there are three available drugs, penicillamine and trientine (chelating agents), and zinc. Tetrathiomolybdate is another chelating agent still under evaluation. The reproductive ability of women with Wilson disease has improved with the increasing efficiency of these therapies, and therefore pregnancy is becoming more common. It does not seem that the course of the disease is affected by pregnancy, but the problem remains on what is the most adequate therapy during gestation, as the safety of these drugs can not be assured during this period. The authors describe 3 cases of Wilson disease and pregnancy, followed at their centre and discuss the controversy around the use of these drugs for the treatment of the disease during pregnancy and lactation.",Hepatic dysfunction;Penicillamine;Pregnancy;Trientine;Wilson disease;Zinc;adult;article;autosomal recessive inheritance;case report;chromosome 13;clinical feature;copper blood level;disease severity;drug hypersensitivity/si [Side Effect];female;gene location;gold standard;human;laboratory test;liver biopsy;liver dysfunction;neurologic disease/si [Side Effect];recommended drug dose;sideroblastic anemia/si [Side Effect];stomach discomfort/si [Side Effect];systemic lupus erythematosus/si [Side Effect];treatment indication;treatment outcome;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;copper/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/do [Drug Dose];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/do [Drug Dose];zinc/dt [Drug Therapy],"Castro, M. G.;Sousa, R.;Marta, S.;Braga, J.",2009,August,,0,0,
1869,Zinc acetate dihydrate - Oral administration (Wilzin). [French],,drug absorption;drug elimination;gastrointestinal symptom/si [Side Effect];human;medical research;short survey;Wilson disease/dt [Drug Therapy];unclassified drug;wilzin;zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration];zinc acetate/pk [Pharmacokinetics],Anonymous,2009,September,,0,0,
1870,Fulminant and subfulminant hepatitis: causes and treatment. [French],"Fulminant hepatitis is an emergency because within a few hours, the physician must find the cause of the hepatitis (not identified in 15 to 20% of cases), rule out any contraindication to liver transplantation, verify that it is indicated, and prevent and/or treat the complications associated with liver failure. Viruses (especially hepatitis viruses A and B), drugs, and toxic agents are the most common causes of fulminant hepatitis, with the proportions varying between countries. Hepatitis viruses, the leading cause through 1995-1996, have fallen behind drugs and in particular paracetamol, which is now the leading cause of this disease in Europe and in the United States. There are also other rarer causes: other viruses (e.g., herpes virus HSV1 or 2, hepatitis virus E, parvovirus B19, and chickenpox-herpes zoster), Wilson Disease, acute Budd-Chiari and Reyes syndromes, autoimmune hepatitis, neoplastic infiltration of the liver, hypoxic hepatitis, heatstroke, acute pregnancy-related steatosis, and the HELLP syndrome. Prognosis is essentially determined by neurological status, but is also affected very rapidly by damage to other organs. Liver transplantation has revolutionized the prognosis of fulminant hepatitis, causing survival to increase from 10-20% (all causes combined) to 75-80% at 1 year and 70% at 5 years. These patients can be treated only in specialized centers with access to liver transplantation and to different modern means of liver resuscitation (hypothermia, artificial liver support, albumin dialysis, monitoring intracranial pressure and cerebral perfusion, etc.) - all from the onset of the disease. © 2009 Elsevier Masson SAS. All rights reserved.",albumin dialysis;autoimmune hepatitis/dt [Drug Therapy];bacterial infection/dt [Drug Therapy];brain perfusion;Budd Chiari syndrome;cancer infiltration;drug intoxication/dt [Drug Therapy];emergency treatment;Europe;fatty liver;graft survival;health care access;health care facility;heat stroke;HELLP syndrome;hepatitis/et [Etiology];hepatitis/si [Side Effect];hepatitis/su [Surgery];hepatitis/th [Therapy];Hepatitis A virus;hepatitis B/dt [Drug Therapy];Hepatitis B virus;Hepatitis E virus;hepatitis virus;Herpes simplex virus 1;Herpes simplex virus 2;herpes zoster/dt [Drug Therapy];human;hypoxia/dt [Drug Therapy];induced hypothermia;intracranial hypertension/dt [Drug Therapy];intracranial pressure monitoring;liver failure/co [Complication];liver failure/pc [Prevention];liver support;liver transplantation;neurologic disease;Parvovirus;pathogenesis;patient care;pregnancy;prognosis;resuscitation;Reye syndrome;short survey;treatment contraindication;treatment indication;United States;Varicella zoster virus;Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];acetylsalicylic acid/to [Drug Toxicity];aciclovir/dt [Drug Therapy];aciclovir/iv [Intravenous Drug Administration];amoxicillin/dt [Drug Therapy];amphetamine/to [Drug Toxicity];benzodiazepine/to [Drug Toxicity];cephalosporin/dt [Drug Therapy];entecavir/dt [Drug Therapy];indometacin/dt [Drug Therapy];lamivudine/dt [Drug Therapy];mannitol/dt [Drug Therapy];opiate/to [Drug Toxicity];oxygen/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];phenytoin/dt [Drug Therapy];prednisolone/dt [Drug Therapy];tenofovir/dt [Drug Therapy];tenofovir disoproxil;tricyclic antidepressant agent/to [Drug Toxicity],"Ichai, P.;Saliba, F.",2009,September,http://dx.doi.org/10.1016/j.lpm.2009.05.004,0,0,
1871,Acute repeating hemolytic anemia as the first manifestation of Wilson's disease: Report of a case. [French],"Introduction: The liver and central nervous system are the usual targets of Wilson's disease, an inherited disorder of copper metabolism. Severe hemolytic anemia is an unusual complication of Wilson's disease. Exegesis: We report a case of Wilson's disease revealed by acute intravascular repeating hemolytic anemia associated with liver failure. The initially negative etiologic investigation was directed by occurred of liver failure. The genetic study allowed to discover an other similar case. The evolution was favourable under treatment with zinc sulfate and penicillamine. Discussion: Diagnosis of Wilson's disease must be considered in case of acute hemolytic anemia associated with liver failure in young adults. © 2009 Elsevier Masson SAS. All rights reserved.",Haemolytic anemia;Liver failure;Wilson's disease;acute disease;adult;article;case report;clinical feature;diagnostic procedure;disease association;genetic analysis;hemolytic anemia/dt [Drug Therapy];hemolytic anemia/di [Diagnosis];human;laboratory test;liver failure/di [Diagnosis];physical examination;Wilson disease/di [Diagnosis];zinc sulfate/dt [Drug Therapy],"El Khattabi, A.;Seddik, H.;Fatihi, J.;Salaheddine, H.;Badaoui, M.;Amezyane, T.;Mahassine, F.;Ohayon, V.",2009,March,http://dx.doi.org/10.1016/j.tracli.2009.01.005,0,0,
1872,Wilson disease. [French],"Wilson Disease must be considered in very varied circumstances, including in patients older than 50 years. Its diagnosis is not based on a single test but on a group of findings. The copper levels may be difficult to interpret. Molecular biology can confirm the diagnosis in only 80% of cases. The advice of the reference center is necessary before beginning treatment: chelators or zinc salts. Lifetime treatment is required. Follow-up of these patients must be regular and multidisciplinary and should be conducted in association with the reference center. Inclusion in the national registry for Wilson Disease must be suggested to all patients. Contact: cmr.wilson@lrb.aphp.fr. © 2009.",clinical feature;copper blood level;copper metabolism;disease registry;drug efficacy;follow up;genetic polymorphism;human;laboratory test;liver transplantation;long term care;molecular biology;mutational analysis;nuclear magnetic resonance imaging;pathophysiology;patient monitoring;protein transport;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];wilzin;zinc derivative/dt [Drug Therapy],"Trocello, J. M.;Chappuis, P.;Chaine, P.;Remy, P.;Debray, D.;Duclos-Vallee, J. C.;Woimant, F.",2009,July/August,http://dx.doi.org/10.1016/j.lpm.2008.11.017,0,0,
1873,Acquired hepatocerebral degeneration,"Cirrhosis and its co-morbidities may cause a variety of neurological complications, the most common being bouts of toxic metabolic encephalopathy. A proportion of patients with chronic liver disease develop acquired hepatocerebral degeneration (AHD), a chronic progressive neurological syndrome characterized by parkinsonism, ataxia and other movement disorders. This article reviews the clinical spectrum, pathophysiology, neuroimaging features and differential diagnosis of AHD along with emerging treatment options. © 2009 Steinkopff-Verlag.",Acquired hepatocerebral degeneration;Cirrhosis;Movement disorder;Portosystemic shunt;ataxia;clinical feature;differential diagnosis;disease course;human;mood change;motor dysfunction;nephrotoxicity/si [Side Effect];neuroimaging;parkinsonism/si [Side Effect];pathogenesis;pathophysiology;priority journal;review;side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];antibiotic agent;beta adrenergic receptor blocking agent/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];edetic acid/ae [Adverse Drug Reaction];edetic acid/dt [Drug Therapy];edetic acid/iv [Intravenous Drug Administration];lactulose/dt [Drug Therapy];levodopa/dt [Drug Therapy];tetrabenazine/ae [Adverse Drug Reaction];tetrabenazine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Ferrara, J.;Jankovic, J.",2009,March,http://dx.doi.org/10.1007/s00415-009-0144-7,0,0,
1874,ICU Management of Acute Liver Failure,"Survival of patients presenting with acute liver failure (ALF) has improved because of earlier disease recognition, better understanding of pathophysiology of various insults leading to ALF, and advances in supportive measures including a team approach, better ICU care, and liver transplantation. This article focuses on patient management and evaluation that takes place in the ICU for patients who have acute liver injury. An organized team approach to decision making about critical care delivered during this period of time is important for achieving a good patient outcome. © 2009 Elsevier Inc. All rights reserved.",Acute liver failure;Cerebral edema;Coagulopathy;Hypothermia;Liver assist devices;Liver transplant;adrenal insufficiency/dt [Drug Therapy];albumin dialysis;alcohol liver cirrhosis;allergy/si [Side Effect];Amanita phalloides;analgesia;artificial ventilation;autoimmune hepatitis/dt [Drug Therapy];bleeding/dt [Drug Therapy];blood clotting disorder;brain edema/th [Therapy];brain hemorrhage;Budd Chiari syndrome/di [Diagnosis];chelation therapy;clinical assessment;clinical evaluation;clinical trial;consultation;continuous hemofiltration;Cytomegalovirus;diagnostic imaging;disease association;disease exacerbation/si [Side Effect];drug hypersensitivity/dt [Drug Therapy];drug megadose;drug withdrawal;Epstein Barr virus;fatty liver/di [Diagnosis];fatty liver/et [Etiology];gastrointestinal symptom;heart arrhythmia/co [Complication];heart arrhythmia/dt [Drug Therapy];heart arrhythmia/si [Side Effect];heart disease;HELLP syndrome;hemodynamics;hepatic encephalopathy/di [Diagnosis];hepatic encephalopathy/si [Side Effect];hepatitis/dt [Drug Therapy];hepatitis/pc [Prevention];Hepatitis A virus;Hepatitis B virus;Hepatitis delta virus;Hepatitis E virus;Herpes simplex virus;human;hypercoagulability;hyperemia/dt [Drug Therapy];hyperemia/pc [Prevention];hypofibrinogenemia;hypoglycemia/th [Therapy];hypothermia/co [Complication];immune mediated injury/et [Etiology];induced hypothermia;infection/dt [Drug Therapy];intensive care;intensive care unit;intracranial hypertension/di [Diagnosis];intracranial hypertension/th [Therapy];intracranial pressure monitoring;kidney failure/th [Therapy];laboratory test;liver biopsy;liver failure/si [Side Effect];liver failure/di [Diagnosis];liver failure/dt [Drug Therapy];liver failure/et [Etiology];liver failure/su [Surgery];liver failure/th [Therapy];liver ischemia;liver support;liver toxicity/et [Etiology];liver toxicity/si [Side Effect];liver transplantation;metabolic disorder/et [Etiology];metabolic disorder/th [Therapy];multiple organ failure;nutrition;nutritional requirement;outcome assessment;pain/dt [Drug Therapy];pathogenesis;patient assessment;positive end expiratory pressure;priority journal;renal replacement therapy;respiratory failure/th [Therapy];review;risk benefit analysis;sedation;seizure/dt [Drug Therapy];septic shock;single drug dose;survival rate;survival time;thorax radiography;toxicokinetics;Varicella zoster virus;vascular access device;vein catheterization;virus hepatitis/dt [Drug Therapy];virus hepatitis/et [Etiology];vitamin K deficiency/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];acetylcysteine/ae [Adverse Drug Reaction];acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];acetylcysteine/po [Oral Drug Administration];acetylcysteine/pk [Pharmacokinetics];amiodarone/to [Drug Toxicity];amiodarone/pk [Pharmacokinetics];antibiotic agent/dt [Drug Therapy];antibiotic agent/po [Oral Drug Administration];antihistaminic agent/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];barbituric acid derivative/dt [Drug Therapy];copper/to [Drug Toxicity];corticosteroid/dt [Drug Therapy];corticotropin/do [Drug Dose];disulfiram/to [Drug Toxicity];disulfiram/pk [Pharmacokinetics];fentanyl/ae [Adverse Drug Reaction];fentanyl/dt [Drug Therapy];glucose/dt [Drug Therapy];glucose/iv [Intravenous Drug Administration];halothane/to [Drug Toxicity];hypertensive agent/dt [Drug Therapy];hypertensive agent/pd [Pharmacology];indometacin/dt [Drug Therapy];isoniazid/to [Drug Toxicity];isoniazid/pk [Pharmacokinetics];ketoconazole/to [Drug Toxicity];ketoconazole/pk [Pharmacokinetics];mannitol/ct [Clinical Trial];mannitol/dt [Drug Therapy];morphine/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];paracetamol/to [Drug Toxicity];paracetamol/pk [Pharmacokinetics];penicillin G/dt [Drug Therapy];pethidine/dt [Drug Therapy];phenytoin/dt [Drug Therapy];recombinant blood clotting factor 7a/dt [Drug Therapy];silibinin/dt [Drug Therapy];steroid/do [Drug Dose];steroid/dt [Drug Therapy];unindexed drug;valproic acid/to [Drug Toxicity];valproic acid/pk [Pharmacokinetics];vitamin K group/dt [Drug Therapy];vitamin K group/iv [Intravenous Drug Administration];zinc/dt [Drug Therapy],"Schilsky, M. L.;Honiden, S.;Arnott, L.;Emre, S.",2009,March,http://dx.doi.org/10.1016/j.ccm.2008.10.001,0,0,
1875,Genetics and Treatment of Dystonia,"The torsion dystonias encompass a broad collection of etiologic subtypes, often divided into primary and secondary classes. Tremendous advances have been made in uncovering the genetic basis of dystonia, including discovery of a gene causing early onset primary torsion dystonia-a GAG deletion in exon 5 of the DYT1 gene that encodes torsinA. Although the exact function of torsinA remains elusive, evidence suggests aberrant localization and interaction of mutated protein; this may result in an abnormal response to stress or interference with cytoskeletal events and the development of neuronal brain pathways. Breakthroughs include the discovery of a genetic modifier that protects against clinical expression in DYT1 dystonia and the identification of the gene causing DYT6, THAP1. The authors review genetic etiologies and discuss phenotypes as well as counseling of patients regarding prognosis and progression of the disease. They also address pharmacologic and surgical treatment options for various forms of dystonia. © 2009 Elsevier Inc. All rights reserved.",Basal ganglia;Botulinum toxin;Deep brain stimulation;Dystonia;dyt1;Genetics;amino acid substitution;autosomal dominant inheritance;autosomal recessive inheritance;blepharospasm/dt [Drug Therapy];brain depth stimulation;cervical dystonia/dr [Drug Resistance];cervical dystonia/dt [Drug Therapy];cervical dystonia/th [Therapy];choreoathetosis;clinical trial;confusion/si [Side Effect];disease classification;drug dose increase;drug dose titration;drug efficacy;drug mechanism;drug response;drug tolerability;dysphagia/si [Side Effect];dystonia/dr [Drug Resistance];dystonia/dt [Drug Therapy];dystonia/et [Etiology];dystonia/su [Surgery];dystonia/th [Therapy];focal dystonia/dt [Drug Therapy];focal dystonia/et [Etiology];gene deletion;gene mutation;gene overexpression;genetic analysis;genetic counseling;hallucination/si [Side Effect];human;injection site pain/si [Side Effect];low drug dose;memory disorder/si [Side Effect];multifocal dystonia;myoclonus dystonia/dt [Drug Therapy];myoclonus dystonia/et [Etiology];nonhuman;nucleotide sequence;orthosis;pathophysiology;penetrance;phenotype;physiotherapy;priority journal;rapid onset dystonia parkinsonism/et [Etiology];review;sedation;segawa disease/dt [Drug Therapy];segawa disease/et [Etiology];segmental dystonia/dt [Drug Therapy];segmental dystonia/et [Etiology];side effect/si [Side Effect];single nucleotide polymorphism;therapy resistance;torsion dystonia;Wilson disease/dt [Drug Therapy];x linked dystonia parkinsonism/et [Etiology];xerostomia/si [Side Effect];alpha sarcoglycan/ec [Endogenous Compound];baclofen/dt [Drug Therapy];baclofen/tl [Intrathecal Drug Administration];baclofen/po [Oral Drug Administration];benzodiazepine derivative/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];botulinum toxin/im [Intramuscular Drug Administration];botulinum toxin/pd [Pharmacology];botulinum toxin A/ae [Adverse Drug Reaction];botulinum toxin A/cm [Drug Comparison];botulinum toxin A/dt [Drug Therapy];botulinum toxin B/ae [Adverse Drug Reaction];botulinum toxin B/cm [Drug Comparison];botulinum toxin B/dt [Drug Therapy];carbidopa/cb [Drug Combination];carbidopa/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];clonazepam/dt [Drug Therapy];cyclobenzaprine/dt [Drug Therapy];diazepam/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];epsilon sarcoglycan/ec [Endogenous Compound];gamma sarcoglycan/ec [Endogenous Compound];levodopa/cb [Drug Combination];levodopa/dt [Drug Therapy];lorazepam/dt [Drug Therapy];mexiletine/dt [Drug Therapy];morphine sulfate/dt [Drug Therapy];oxybate sodium/ct [Clinical Trial];oxybate sodium/dt [Drug Therapy];parkin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];sepiapterin reductase/ec [Endogenous Compound];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dt [Drug Therapy];tizanidine/dt [Drug Therapy];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trihexyphenidyl/ae [Adverse Drug Reaction];trihexyphenidyl/dt [Drug Therapy];unindexed drug;zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];zolpidem/dt [Drug Therapy],"Schwarz, C. S.;Bressman, S. B.",2009,August,http://dx.doi.org/10.1016/j.ncl.2009.04.010,0,0,
1876,Diagnosis and management of metabolic liver failure in children. [French],,article;child;congenital disorder of glycosylation;disorders of mitochondrial functions;galactosemia/cn [Congenital Disorder];hemochromatosis;hereditary fructose intolerance;human;liver failure/di [Diagnosis];liver failure/et [Etiology];Niemann Pick disease;tyrosinemia;Wilson disease;antibiotic agent;antioxidant;benzoic acid;carnitine/iv [Intravenous Drug Administration];glucose/iv [Intravenous Drug Administration];mannose/po [Oral Drug Administration];penicillamine;trientine,"Broue, P.;Baruteau, J.",2009,June,http://dx.doi.org/10.1016/S0929-693X%2809%2974096-5,0,0,
1877,Role of genotyping in Wilson's disease,,alanine aminotransferase blood level;autosomal recessive inheritance;cation transport;ceruloplasmin blood level;chromosome 13;copper blood level;copper metabolism;editorial;genetic epigenesis;genetic screening;genetic trait;genotype;hemolysis;homozygosity;liver carcinogenesis;liver failure;mental disease;missense mutation;nerve degeneration;onset age;oxidative stress;prevalence;priority journal;protein phosphorylation;single nucleotide polymorphism;treatment response;Wilson disease;adenosine triphosphatase;alanine aminotransferase;ceruloplasmin;copper;penicillamine;zinc,"Schmidt, H. H. J.",2009,March,http://dx.doi.org/10.1016/j.jhep.2008.11.008,0,0,
1878,Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin,"Wilson disease (WD) is an autosomal recessive copper overload disorder of the liver and basal ganglia. WD is caused by mutations in the gene encoding ATP7B, a protein localized to the trans-Golgi network that primarily facilitates hepatic copper excretion. Current treatment comprises reduction of circulating copper by zinc supplementation or copper chelation. Despite treatment, a significant number of patients have neurological deterioration. The aim of this study was to investigate the possibility that defects arising from some WD mutations are ameliorated by drug treatment aimed at improvement of protein folding and restoration of protein function. This necessitated systematic characterization of the molecular consequences of distinct ATP7B missense mutations associated with WD. With the exception of p.S1363F, all mutations tested (p.G85V, p.R778L, p.H1069Q, p.C1104F, p.V1262F, p.G1343V, and p.S1363F) resulted in reduced ATP7B protein expression, whereas messenger RNA abundance was unaffected. Retention of mutant ATP7B in the endoplasmic reticulum, increased protein expression, and normalization of localization after culturing cells at 30degree C, and homology modeling suggested that these proteins were misfolded. Four distinct mutations exhibited residual copper export capacity, whereas other mutations resulted in complete disruption of copper export by ATP7B. Treatment with pharmacological chaperones 4-phenylbutyrate (4-PBA) and curcumin, a clinically approved compound, partially restored protein expression of most ATP7B mutants. Conclusion: These findings might enable novel treatment strategies in WD by directly enhancing the protein expression of mutant ATP7B with residual copper export activity. Copyright © 2009 by the American Association for the Study of Liver Diseases.",article;cell strain Hek293;conformational transition;controlled study;drug activity;endoplasmic reticulum;fluorescence microscopy;gene mutation;genetic transfection;human;human cell;human cell culture;missense mutation;mutant;pathogenesis;precipitation;priority journal;protein expression;protein folding;protein function;protein localization;protein protein interaction;reverse transcription polymerase chain reaction;temperature;Western blotting;Wilson disease/et [Etiology];4 phenylbutyric acid/pd [Pharmacology];chaperone;copper;curcumin/pd [Pharmacology];messenger RNA/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound],"Van Den Berghe, P. V. E.;Stapelbroek, J. M.;Krieger, E.;De Bie, P.;Van De Graaf, S. F. J.;De Groot, R. E. A.;Van Beurden, E.;Spijker, E.;Houwen, R. H. J.;Berger, R.;Klomp, L. W. J.",2009,,http://dx.doi.org/10.1002/hep.23209,0,0,
1879,Copper-Associated Liver Diseases,"The liver is essential for copper metabolism. Copper metabolism is highly conserved between different species. This article provides the reader with an overview of copper storage disorders in humans and animals. Diagnosis and treatment of copper-associated hepatitis are described, and breed-specific characteristics of the disease are explained. A literature review references publications about the disease in companion animals. © 2009 Elsevier Inc. All rights reserved.","Centro-lobular copper;Diet;Heritability;Metabolic disease;Wilson's disease;anemia/si [Side Effect];autoimmune disease/si [Side Effect];bone marrow suppression/si [Side Effect];chelation therapy;chronic hepatitis/di [Diagnosis];chronic hepatitis/dt [Drug Therapy];copper deficiency/si [Side Effect];copper metabolism;cytopenia/si [Side Effect];diet therapy;dog disease;drug blood level;drug eruption/si [Side Effect];drug fever/si [Side Effect];hemolysis/dt [Drug Therapy];human;intoxication/dt [Drug Therapy];intoxication/th [Therapy];intrahepatic cholestasis;liver biopsy;liver cirrhosis;liver disease;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];Menkes syndrome;nonhuman;oxidative stress;proteinuria/si [Side Effect];quantitative analysis;recommended drug dose;review;systemic lupus erythematosus/si [Side Effect];toxic hepatitis/dt [Drug Therapy];vitamin deficiency/si [Side Effect];Wilson disease/dt [Drug Therapy];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];gluconate zinc/dt [Drug Therapy];n,n' bis(2 aminoethyl) 1,3 propanediamine/ae [Adverse Drug Reaction];n,n' bis(2 aminoethyl) 1,3 propanediamine/dt [Drug Therapy];n,n' bis(2 aminoethyl) 1,3 propanediamine/to [Drug Toxicity];n,n' bis(2 aminoethyl) 1,3 propanediamine/po [Oral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/po [Oral Drug Administration];placebo;prednisolone/dt [Drug Therapy];tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/iv [Intravenous Drug Administration];zinc/cr [Drug Concentration];zinc/po [Oral Drug Administration]","Hoffmann, G.",2009,May,http://dx.doi.org/10.1016/j.cvsm.2009.02.001,0,0,
1880,Diagnosis and Epidemiology of Cirrhosis,"Cirrhosis is defined histologically as an advanced form of progressive hepatic fibrosis with distortion of the hepatic architecture and regenerative nodule formation. It may be due to a variety of causes. It can be diagnosed incidentally on liver biopsy or hepatic imaging studies, or patients may present clinically with one or more features of hepatic failure. This article gives the reader a broad overview of the epidemiology, diagnosis, and natural history of cirrhosis; laying the foundation for subsequent articles, which will discuss the diagnosis and management of each of the specific cirrhosis-related complications. © 2009 Elsevier Inc. All rights reserved.",Causes;Cirrhosis;Clinical course;Labs;Radiology;alcohol consumption;alcohol liver disease;alpha 1 antitrypsin deficiency;autoimmune hepatitis;clinical feature;computer assisted tomography;disease association;disease course;echography;hemochromatosis;hepatitis A;hepatitis B;hepatitis C/dt [Drug Therapy];hepatitis E;histopathology;human;liver biopsy;liver cirrhosis/si [Side Effect];liver cirrhosis/di [Diagnosis];liver cirrhosis/ep [Epidemiology];liver cirrhosis/et [Etiology];nonalcoholic fatty liver;nuclear magnetic resonance imaging;primary biliary cirrhosis;primary sclerosing cholangitis;priority journal;prothrombin time;review;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];alpha 2 macroglobulin/ec [Endogenous Compound];amiodarone/ae [Adverse Drug Reaction];apolipoprotein A1/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];haptoglobin/ec [Endogenous Compound];immunoglobulin/ec [Endogenous Compound];interferon/dt [Drug Therapy];methotrexate/ae [Adverse Drug Reaction];methyldopa/ae [Adverse Drug Reaction];nitrofurantoin/ae [Adverse Drug Reaction];oxyphenisatine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];ribavirin/dt [Drug Therapy];trientine/dt [Drug Therapy],"Lefton, H. B.;Rosa, A.;Cohen, M.",2009,July,http://dx.doi.org/10.1016/j.mcna.2009.03.002,0,0,
1881,Elastosis perforans serpiginosa and cutis laxa caused by prolonged treatment of Wilson's disease with D-penicillamine. [Dutch],"In this case-report we present a 34-year-old patient with Wilson's disease who had been treated with D-penicillamine for 27 years. After 19 years of treatment she developed a slack skin of her neck and axillary folds (cutis laxa) and erythematous papules with hyperkeratotic plugs (elastosis perforans serpiginosa). Histopathology revealed transepidermal elimination of ""lumpy-bumpy"" or ""bramble-bush"" elastic fibers, pathognomic of longterm D-penicillamine use. Therapy is usually difficult, currently treatment consisting of intralesional Kenacort injections are moderately successful.",Bramble-bush elastic fiber;Cutis laxa;D-penicillamine;Elastosis perforans serpiginosa;Lumpy-bumpy elastic fiber;adult;article;case report;cutis laxa/si [Side Effect];drug hypersensitivity/si [Side Effect];drug use;elastic fiber;elastosis perforans serpiginosa/si [Side Effect];female;histopathology;human;human tissue;lumpy skin disease;skin disease/si [Side Effect];skin manifestation/si [Side Effect];tissue structure;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Vellinga, D.;Boom, B. W.;Vermeer, M. H.",2009,August,,0,0,
1882,Elastoris perforans serpiginosa in a patient with Wilson's disease treated with penicillamine. [Spanish],"Elastosis Perforans Serpiginosa belongs to perforating diseases of the skin. It is a rare condition that appears in early ages, childhood or early adult age. Almost half of the cases are related to different genetic alterations or prolonged treatments with penicillamine. The lesions are queratotic papules of 2-5mm with serpiginous or annular pattern, and the neck and the flexures are the most frequent locations. The principal anatomopathologic characteristics are hiperplasic and transepidermal elimination of elastic fiber. We show a patient with 48 years old, with Wilson's disease in treatment with D-penicillamine, who consulted by annular repetitive lesions and spontaneous resolution.",D-penicillamine;Elastosis perforans serpiginosa;Perforating diseases;Wilson's disease;adult;article;case report;disease course;drug induced disease/co [Complication];drug induced disease/et [Etiology];elastic fiber;elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/et [Etiology];epidermis;female;human;hyperplasia;neck;onset age;skin disease/si [Side Effect];skin disease/di [Diagnosis];skin disease/et [Etiology];skin manifestation;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Almazan-Fernandez, F. M.;Abad-Romero, J.;Hernandez-Gil Sanchez, J.;Naranjo-Sintes, R.",2009,May-June,,0,0,
1883,Zinc acetate dihydrate - oral administration (Wilzin). [Dutch],,drug absorption;human;intestine absorption;note;treatment contraindication;treatment indication;Wilson disease/dt [Drug Therapy];unclassified drug;wilzin;zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration];zinc acetate/pk [Pharmacokinetics];zinc acetate/pd [Pharmacology],"Duh, D.;Van Melkebeke, B.",2009,September,,0,0,
1884,Copper compounds in anticancer strategies,"The chemical properties of copper allow it to take part in many biological functions such as electron transfer, catalysis, and structural shaping. The ability to cycle between +1 and +2 oxidation state is one of the features that has been exploited by organisms throughout the evolutionary process. Since copper is potentially toxic to cells also a finely controlled mechanism for copper handling has evolved. On the other side, many copper complexes were synthesized and tested for their anticancer activity in vitro and in vivo. Their ability to kill cancer cells is mainly related to the induction of an oxidative stress, but recently it emerged their ability to inhibit the proteasome, a protein complex whose proteolitic activity is needed by several cellular process. It has generally been described that the toxic effects of copper complexes leads to cell death either by necrosis or through the activation of the apoptotic process. Evidences are rising about the ability of some copper compounds to induce alternative non-apoptotic form of programmed cell death. Since copper is indispensable for the formation of new blood vessels, angiogenesis, a different antitumor approach based on the administration of copper sequestering agents has been attempted and its effectiveness is currently under evaluation by clinical trials. The proven essentiality of copper for angiogenesis, together with the marked sensitivity shown by several cancer cell lines to the copper toxicity, open a new perspective in the anticancer strategy: exploiting the tumor need of copper to accumulate toxic amount of the metal inside its cells. © 2009 Bentham Science Publishers Ltd.","Apoptosis;Copper complex;Paraptosis;Proteasome inhibition;ros;angiogenesis;antineoplastic activity;brain metastasis/dt [Drug Therapy];brain metastasis/rt [Radiotherapy];breast cancer/dt [Drug Therapy];cancer cell;cancer cell culture;catalysis;cell activity;cell death;cell killing;cell survival;clinical trial;DNA damage;DNA repair;DNA synthesis inhibition;drug structure;electron transport;enzyme inhibition;Fenton reaction;human;in vitro study;in vivo study;inhibition kinetics;malignant neoplastic disease/dr [Drug Resistance];malignant neoplastic disease/dt [Drug Therapy];multiple myeloma/dt [Drug Therapy];nonhuman;oxidation;oxidative stress;prostate cancer/dt [Drug Therapy];protein binding;protein degradation;review;Wilson disease/dt [Drug Therapy];1,10 phenanthroline copper/an [Drug Analysis];1,10 phenanthroline copper/dv [Drug Development];1,10 phenanthroline copper/pd [Pharmacology];benzyloxycarbonylleucylleucylleucinal/pd [Pharmacology];bortezomib/dt [Drug Therapy];bortezomib/pd [Pharmacology];cisplatin;copper derivative/ct [Clinical Trial];copper derivative/an [Drug Analysis];copper derivative/cb [Drug Combination];copper derivative/dv [Drug Development];copper derivative/dt [Drug Therapy];copper derivative/pd [Pharmacology];copper zinc superoxide dismutase/ec [Endogenous Compound];disulfiram/an [Drug Analysis];disulfiram/cb [Drug Combination];disulfiram/dt [Drug Therapy];disulfiram/pd [Pharmacology];doxorubicin;gadolinium texaphyrin/ct [Clinical Trial];gadolinium texaphyrin/dt [Drug Therapy];isatin derivative/an [Drug Analysis];isatin derivative/dv [Drug Development];isatin derivative/pd [Pharmacology];manganese superoxide dismutase/ec [Endogenous Compound];nci 109268/an [Drug Analysis];nci 109268/dv [Drug Development];nci 109268/pd [Pharmacology];nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase/ec [Endogenous Compound];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];poly(adenosine diphosphate ribose)/ec [Endogenous Compound];proteasome/ec [Endogenous Compound];proteasome inhibitor/an [Drug Analysis];proteasome inhibitor/dv [Drug Development];proteasome inhibitor/pd [Pharmacology];pyridoxal/an [Drug Analysis];pyridoxal/dv [Drug Development];pyridoxal/pd [Pharmacology];pyrrolidine dithiocarbamate/cb [Drug Combination];pyrrolidine dithiocarbamate/dt [Drug Therapy];pyrrolidine dithiocarbamate/pd [Pharmacology];quinolinol derivative/an [Drug Analysis];quinolinol derivative/dv [Drug Development];quinolinol derivative/pd [Pharmacology];reactive oxygen metabolite/ec [Endogenous Compound];ribonucleotide reductase/ec [Endogenous Compound];salicylaldehyde/an [Drug Analysis];salicylaldehyde/dv [Drug Development];salicylaldehyde/pd [Pharmacology];tetrathiomolybdic acid/an [Drug Analysis];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];thiophene derivative/an [Drug Analysis];thiophene derivative/dv [Drug Development];thiophene derivative/pd [Pharmacology];thiosemicarbazone derivative/an [Drug Analysis];thiosemicarbazone derivative/dv [Drug Development];thiosemicarbazone derivative/pd [Pharmacology];trientine/an [Drug Analysis];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];unclassified drug;unindexed drug;uracil derivative/an [Drug Analysis];uracil derivative/dv [Drug Development];uracil derivative/pd [Pharmacology];vasculotropin/ec [Endogenous Compound]","Tardito, S.;Marchio, L.",2009,,http://dx.doi.org/10.2174/092986709787846532,0,0,
1885,Wilson's disease,,Inborn errors of metabolism;Review;Wilson's disease;article;bone marrow suppression/si [Side Effect];central nervous system disease;clinical feature;drug dose increase;drug efficacy;drug response;eye disease;gene mutation;histopathology;human;intestine absorption;liver disease;liver failure/su [Surgery];liver function test;liver transplantation;mental disease;molecular biology;nephrotoxicity/si [Side Effect];neurologic disease/si [Side Effect];pathophysiology;patient compliance;physical examination;prevalence;priority journal;side effect/si [Side Effect];skin disease/si [Side Effect];treatment indication;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/do [Drug Dose];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Gouider-Khouja, N.",2009,December,http://dx.doi.org/10.1016/S1353-8020%2809%2970798-9,0,0,
1886,MR imaging of the Wilson's disease,"Wilson's disease is known to have various hepatic manifestations like acute hepatitis, chronic hepatitis, cirrhosis of liver and acute fulminant hepatic failure can occur in early childhood. However, we report here Wilson's disease, presented with neurological manifestations without hepatic involvement.",Hepatic;Hepatolenticular degenration;Neurological;Wilson's disease;abdominal distension;acute hepatitis;article;case report;child;chronic hepatitis;computer assisted tomography;diagnostic imaging;diffusion weighted imaging;hepatitis;human;laboratory test;liver cirrhosis;liver failure;male;neurologic examination;nuclear magnetic resonance imaging;physical examination;school child;Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];penicillamine/dt [Drug Therapy],"Taksande, A.;Parihar, P. H.;Tayade, A.;Vilhekar, K. Y.",2009,July-September,,0,0,
1887,Is it possible to diagnose Wilson disease with a piece of skin?,"Renal, skeletal, cardiac, and ophthalmic involvement in Wilson disease (WD) is well known. In this case report, high copper content and ultrastructural findings of skin of a patient with WD accompanied by xerosis are presented.",Copper;Skin;Ultrastructure;Wilson disease;Xerosis;alanine aminotransferase blood level;albumin blood level;aminotransferase blood level;article;ascites;aspartate aminotransferase blood level;body height;body surface;body weight;case report;cell nucleus;ceruloplasmin blood level;chelation therapy;child;cholesterol blood level;consanguineous marriage;controlled study;cytoplasm;dehydration;dermis;desmosome;Doppler flowmetry;dry skin;edema;electrolyte blood level;electron microscopy;eye examination;fibroblast;follow up;hemoglobin blood level;hepatosplenomegaly;human;human tissue;hyperkeratosis;hypoalbuminemia;intercellular space;international normalized ratio;jaundice;leg;leukocyte count;lysosome;male;medical record;microscopy;neurologic examination;palliative therapy;palpation;partial thromboplastin time;patient referral;portal hypertension;portosystemic anastomosis;priority journal;protein blood level;prothrombin time;school child;sibling;skin biopsy;skin edema;skin exfoliation;spleen;splenorenal shunt;thrombocyte count;tonofilament;triacylglycerol blood level;urine level;Wilson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];xerosis/dt [Drug Therapy];acetone;alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];cholesterol/ec [Endogenous Compound];citric acid;copper/ec [Endogenous Compound];electrolyte/ec [Endogenous Compound];emollient agent/dt [Drug Therapy];glutaraldehyde;hemoglobin/ec [Endogenous Compound];lead;paraffin;penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];protein/ec [Endogenous Compound];sodium dihydrogen phosphate;triacylglycerol/ec [Endogenous Compound];uranyl acetate;zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Esrefoglu, M.;Gu, M.;Seyhan, M.;Selimoglu, M. A.",2009,,http://dx.doi.org/10.3109/01913120903348852,0,0,
1888,Wilson's disease: Two treatment modalities. Correlations to pretreatment and posttreatment brain MRI,"Introduction: Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Methods: Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. Results: MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. Conclusions: From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P. © 2009 Springer-Verlag.",D-penicillamine;Neuroimaging;Treatment;Wilson's disease;Zinc;adolescent;adult;article;ataxia;athetosis;brain cortex;brain stem;cerebellum;child;chorea;clinical article;controlled study;correlation analysis;disease severity;dysarthria;dysphagia;dystonia;female;follow up;human;male;mental disease;muscle spasm;nuclear magnetic resonance imaging;olivary nucleus;parkinsonism;priority journal;proton nuclear magnetic resonance;sardonic grin;school child;thalamus;tremor;white matter;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Leiros Da Costa, M. D. D.;Spitz, M.;Bacheschi, L. A.;Leite, C. C.;Lucato, L. T.;Barbosa, E. R.",2009,October,http://dx.doi.org/10.1007/s00234-009-0536-5,0,1,
1889,Carlecortemcel-l: An ex vivo expanded umbilical cord blood cell graft for allogeneic transplantation,"Background: Success of umbilical cord blood transplantation (UCBT) is mostly affected by the cell dose infused and its application is limited by the size of the recipient. For most adults and older children it is not possible to find a single UCB unit large enough for reliable engraftment. One strategy to increase the number of progenitor cells available is ex vivo expansion of the unit. The main challenge of ex vivo expansion systems is how not to deplete the self-renewing cell population by driving them into differentiation into committed progenitors. Objective: Copper modulates basic cell functions, such as survival, proliferation, and differentiation. Reduction of cellular copper in ex vivo culture conditions enabled preferential proliferation of early progenitors and increased engraftment capabilities. The result of a Phase I study of carlecortemcel-l, a product derived from ex vivo expansion of UCB progenitors in the presence of a copper chelator and early-acting cytokines, and the study design for the current pivotal study are presented. Methods: A literature review using PubMed and the investigator's brochure from the manufacturer. Conclusions: Early results suggest that carlecortemcel-l infusion is safe and may be associated with favorable non-relapse mortality rates. A pivotal global study is currently being conducted to evaluate safety and efficacy of this product from centralized manufacturing facilities. © 2009 Informa UK Ltd. All rights reserved.",Carlecortemcel-l;Copper chelation;Early hematopoietic progenitors;Ex vivo expansion;StemEx;Umbilical cord blood transplantation;acute lymphoblastic leukemia/dt [Drug Therapy];acute lymphoblastic leukemia/su [Surgery];acute lymphoblastic leukemia/th [Therapy];acute myeloblastic leukemia/dt [Drug Therapy];acute myeloblastic leukemia/su [Surgery];acute myeloblastic leukemia/th [Therapy];allotransplantation;bioreactor;cell differentiation;cell function;cell proliferation;cell survival;clinical trial;cord blood stem cell transplantation;drug effect;ex vivo study;graft versus host reaction/co [Complication];graft versus host reaction/dt [Drug Therapy];graft versus host reaction/pc [Prevention];hematopoietic stem cell;Hodgkin disease/dt [Drug Therapy];Hodgkin disease/su [Surgery];Hodgkin disease/th [Therapy];human;nonhodgkin lymphoma/dt [Drug Therapy];nonhodgkin lymphoma/su [Surgery];nonhodgkin lymphoma/th [Therapy];nonhuman;review;Wilson disease/dt [Drug Therapy];antineoplastic agent/ct [Clinical Trial];antineoplastic agent/dt [Drug Therapy];antineoplastic agent/iv [Intravenous Drug Administration];antineoplastic agent/pa [Parenteral Drug Administration];antineoplastic agent/pd [Pharmacology];carlecortemcel L/ct [Clinical Trial];carlecortemcel L/dt [Drug Therapy];carlecortemcel L/iv [Intravenous Drug Administration];carlecortemcel L/pa [Parenteral Drug Administration];carlecortemcel L/pd [Pharmacology];copper;methotrexate/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];TEPA/pd [Pharmacology];trientine/dt [Drug Therapy];unclassified drug,"Petropoulos, D.;Ka, W. C.",2009,October,http://dx.doi.org/10.1517/14712590903321447,0,0,
1890,Potential of vitamin E as an antioxidant adjunct in Wilson's disease,"Wilson's disease is a rare genetic illness of copper metabolism, which leads to copper-overload in mitochondria and organ damage, especially to the liver. Oxidative stress is central to the pathogenesis and a case is briefly made for rigorous trials of vitamin E as an antioxidant adjunct based on earlier corollary studies of its levels in the blood and liver of Wilson's disease patients and its effects in animal models of the illness. © 2009 Elsevier Ltd. All rights reserved.",alpha tocopherol deficiency;antioxidant activity;article;copper metabolism;human;lipid peroxidation;nonhuman;oxidative stress;priority journal;vitamin supplementation;Wilson disease/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Fryer, M. J.",2009,December,http://dx.doi.org/10.1016/j.mehy.2009.05.025,0,0,
1891,Anti-copper therapies in Alzheimer's disease: New concepts,"Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disorder. The recent Metal Hypothesis states that the interaction of Amyloid beta (Abeta, the main constituent of senile plaques) with transition metals is at the basis of AD neurodegeneration. This hypothesis is based on in vitro studies demonstrating that metals (copper, zinc) accelerate the aggregation and precipitation into plaques of Abeta, ultimately leading to synaptic dysfunction and accelerated amyloidogenesis. Recently, we have identified in AD patients a specific 'copper disease' marker, consisting in a serum-increase of copper not bound to ceruloplasmin, named 'free' copper. Several patents have been issued in the recent years and many clinical trials have been attempted in search of an anti-metal effect counteracting AD progression. Some of them have delivered very encouraging results. These anti-metal agents, however, have also shown adverse events. This work is aimed at reviewing 'old' and 'new' attitudes towards the use of anti-copper complexing agents or biological molecules which induce or maintain a state of copper malabsorption, such as zinc compounds, paying special attention to how such a rethinking of 'old' clinical trials might trace new routes in planning 'modern' ones. © 2009 Bentham Science Publishers Ltd.","'Free' copper;Alzheimer's disease;Anti-copper agents;Ceruloplasmin;Metal chelators;Metal complexing agents;Serum copper;Zinc therapy;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];anemia/si [Side Effect];ceruloplasmin blood level;chemical interaction;clinical trial;copper blood level;dose response;drug absorption;drug efficacy;drug elimination;drug mechanism;drug screening;drug structure;drug tolerability;heart arrest/si [Side Effect];human;in vitro study;leukopenia/si [Side Effect];liver toxicity/dt [Drug Therapy];liver toxicity/si [Side Effect];metal binding;nonhuman;Parkinson disease/dt [Drug Therapy];priority journal;protein aggregation;review;subacute myelooptic neuropathy/si [Side Effect];trace metal blood level;treatment duration;unspecified side effect/si [Side Effect];vascular amyloidosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];1,2 bis(2 aminophenyloxy)ethane n,n,n',n' bis(2 octadecyloxyethyl)ester n,n' disodium/dv [Drug Development];1,2 bis(2 aminophenyloxy)ethane n,n,n',n' bis(2 octadecyloxyethyl)ester n,n' disodium/dt [Drug Therapy];1,2 bis(2 aminophenyloxy)ethane n,n,n',n' bis(2 octadecyloxyethyl)ester n,n' disodium/pd [Pharmacology];aluminum/pk [Pharmacokinetics];amyloid beta protein/ec [Endogenous Compound];amyloid precursor protein/ec [Endogenous Compound];anti copper complexing agent/ae [Adverse Drug Reaction];anti copper complexing agent/dv [Drug Development];anti copper complexing agent/dt [Drug Therapy];anti copper complexing agent/pd [Pharmacology];bathocuproine/an [Drug Analysis];bathocuproine/pd [Pharmacology];bathophenanthroline/an [Drug Analysis];bathophenanthroline/pd [Pharmacology];beta secretase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/dv [Drug Development];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];clioquinol/ae [Adverse Drug Reaction];clioquinol/ct [Clinical Trial];clioquinol/an [Drug Analysis];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pd [Pharmacology];copper/ec [Endogenous Compound];cupric ion;deferoxamine/ct [Clinical Trial];deferoxamine/an [Drug Analysis];deferoxamine/dt [Drug Therapy];deferoxamine/im [Intramuscular Drug Administration];dp 109;n,n,n',n' tetrakis(2 pyridylmethyl)ethylenediamine/an [Drug Analysis];orotate copper/ct [Clinical Trial];orotate copper/dt [Drug Therapy];orotate copper/po [Oral Drug Administration];orotate copper/pd [Pharmacology];PBT2/ct [Clinical Trial];PBT2/do [Drug Dose];PBT2/dt [Drug Therapy];PBT2/pd [Pharmacology];penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pentetic acid/pd [Pharmacology];phenanthroline/an [Drug Analysis];phenanthroline/pd [Pharmacology];placebo;tetrathiomolybdate ammonium/an [Drug Analysis];tetrathiomolybdate ammonium/cm [Drug Comparison];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/pk [Pharmacokinetics];unclassified drug;wilzin;zinc acetate/cm [Drug Comparison];zinc acetate/po [Oral Drug Administration];zinc aspartate/dt [Drug Therapy];zinc aspartate/iv [Intravenous Drug Administration];zinc aspartate/po [Oral Drug Administration];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/cm [Drug Comparison];zinc derivative/dt [Drug Therapy];zinc derivative/po [Oral Drug Administration];zinc derivative/pd [Pharmacology];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration]","Squitti, R.;Zito, G.",2009,November,http://dx.doi.org/10.2174/157488909789104802,0,0,
1892,Pharmacological therapies for unconjugated hyperbilirubinemia,"Severe unconjugated hyperbilirubinemia, seen mainly in neonates, may cause kernicterus and death. Conventional treatment for severe unconjugated hyperbilirubinemia consists of phototherapy and exchange transfusion. Phototherapy, however, has several known disadvantages while exchange transfusion is associated with a significant morbidity, and even mortality. These harmful effects indicate the need to develop alternative pharmacological treatment strategies for unconjugated hyperbilirubinemia. Generally, these strategies aim to decrease the plasma concentration of unconjugated bilirubin (UCB) by inhibiting production, stimulating hepatic clearance, or interrupting the enterohepatic circulation of the pigment. To be considered for routine clinical use, an alternative treatment strategy should be less invasive and at least as effective and safe as phototherapy. Several pharmacological therapies such as metalloporhyrins, clofibrate, bile salts, laxatives and bilirubin oxidase may meet these criteria in the future, but none of them has yet been evaluated sufficiently to allow routine application. This review aims to discuss the state of the art and future perspectives in pharmacological treatment of neonatal jaundice. © 2009 Bentham Science Publishers Ltd.",Enterohepatic circulation;Hyperbilirubinemia;Jaundice;Neonate;Pharmacological therapy;Phototherapy;absence of side effects/si [Side Effect];add on therapy;anemia/si [Side Effect];antioxidant activity;binding affinity;carcinogenicity;chemical analysis;clinical trial;constipation/si [Side Effect];Crigler Najjar syndrome/dt [Drug Therapy];diarrhea/si [Side Effect];drug blood level;drug efficacy;drug safety;erythrocyte lifespan;exchange blood transfusion;gallstone/si [Side Effect];gastrointestinal symptom/si [Side Effect];Gilbert disease/dt [Drug Therapy];glucose 6 phosphate dehydrogenase deficiency/dt [Drug Therapy];human;hyperbilirubinemia/dt [Drug Therapy];hyperbilirubinemia/th [Therapy];isomerization;liver clearance;macrophage;metabolic acidosis/si [Side Effect];myopathy/si [Side Effect];neurotoxicity;newborn jaundice/th [Therapy];priority journal;protein binding;protein degradation;reticuloendothelial system;review;side effect/si [Side Effect];single drug dose;thrombocyte aggregation;vasodilatation;vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];agar/dt [Drug Therapy];bile salt/cr [Drug Concentration];bile salt/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];biliverdin/ec [Endogenous Compound];calcium phosphate/ae [Adverse Drug Reaction];calcium phosphate/ct [Clinical Trial];calcium phosphate/dt [Drug Therapy];charcoal/dt [Drug Therapy];clofibrate/ae [Adverse Drug Reaction];clofibrate/ct [Clinical Trial];clofibrate/dt [Drug Therapy];clofibrate/po [Oral Drug Administration];colestyramine/ae [Adverse Drug Reaction];colestyramine/dt [Drug Therapy];glutathione transferase/ec [Endogenous Compound];mesoporphyrin/ct [Clinical Trial];mesoporphyrin/dt [Drug Therapy];metalloporphyrin;penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];phenobarbital/ct [Clinical Trial];phenobarbital/dt [Drug Therapy];placebo;tetrahydrolipstatin/ae [Adverse Drug Reaction];tetrahydrolipstatin/ct [Clinical Trial];tetrahydrolipstatin/dt [Drug Therapy];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/cr [Drug Concentration];zinc derivative/do [Drug Dose];zinc derivative/dt [Drug Therapy];zinc derivative/po [Oral Drug Administration],"Cuperus, F. J. C.;Hafkamp, A. M.;Hulzebos, C. V.;Verkade, H. J.",2009,September,http://dx.doi.org/10.2174/138161209789058219,0,0,
1893,Drug development for orphan diseases in the context of personalized medicine,"Orphan diseases are diseases that are found in less than 200,000 patients in the United States, which is the cutoff point for the number of patients for a drug to be profitable. Because many thousands of orphan diseases exist in the aggregate (about 20 to 30 million Americans have orphan diseases), these patients are disenfranchised from drug development by the pharmaceutical industry. Orphan drugs are a large part of personalized medicine. The orphan diseases are often so rare that a physician may observe only 1 case a year or less. So proper treatment is a personalized encounter between doctor and patient. Academic physician-scientists have tried to fill this therapy vacuum by working on developing orphan drugs. But many disincentives are involved, which include career disincentives, lack of funding, and the multiple areas of expertise that are required. Positive developments include formation of the National Organization for Rare Diseases, the Orphan Drug Act, the development of a grant program to fund orphan drug development, the formation of the National Institutes of Health Office of Rare Diseases, and the passage of orphan drug legislation by other countries. Progress has increased, but the 300 orphan drugs and devices approved in the last 25 years are still only a drop in the bucket compared with the many thousands of orphan diseases. I believe we must do better. I present my own 2 examples of the positive and the negative aspects of orphan drug development, and I end this article by giving recommendations on how we might succeed both in developing more orphan drugs and in rescuing the pharmaceutical industry from its impending economic collapse. © 2009 Mosby, Inc. All rights reserved.",absence of side effects/si [Side Effect];aminotransferase blood level;anemia/si [Side Effect];clinical trial;disease exacerbation/si [Side Effect];drug approval;drug dose reduction;drug efficacy;drug industry;drug manufacture;drug research;drug safety;drug screening;food and drug administration;funding;Gaucher disease/dt [Drug Therapy];health program;human;law;leukopenia/si [Side Effect];medicine;microcytosis/si [Side Effect];off label drug use;orphan disease;personalized medicine;priority journal;program development;rare disease;review;sickle cell anemia/dt [Drug Therapy];side effect/si [Side Effect];United States;Wilson disease/dt [Drug Therapy];human growth hormone/pe [Pharmacoeconomics];imiglucerase/dv [Drug Development];imiglucerase/dt [Drug Therapy];imiglucerase/pe [Pharmacoeconomics];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];recombinant erythropoietin/pe [Pharmacoeconomics];rofecoxib;tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/ct [Clinical Trial];zinc/dv [Drug Development];zinc/dt [Drug Therapy];zinc/pe [Pharmacoeconomics];zinc/pk [Pharmacokinetics];zinc/pd [Pharmacology];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/ct [Clinical Trial];zinc acetate/dv [Drug Development];zinc acetate/dt [Drug Therapy],"Brewer, G. J.",2009,December,http://dx.doi.org/10.1016/j.trsl.2009.03.008,0,0,
1894,Metal chelators coupled with nanoparticles as potential therapeutic agents for alzheimer's disease,"Alzheimer's disease (AD) is a devastating neuro-degenerative disorder characterized by the progressive and irreversible loss of memory followed by complete dementia. Despite the disease's high prevalence and great economic and social burden, an explicative etiology or viable cure is not available. Great effort has been made to better understand the disease's pathogenesis and to develop more effective therapeutic agents. However, success is greatly hampered by the presence of the blood-brain barrier, which limits a large number of potential therapeutics from entering the brain. Nanoparticle-mediated drug delivery is one of the few valuable tools for overcoming this impediment, and its application as a potential AD treatment shows promise. In this review, the current studies on nanoparticle delivery of chelation agents as possible therapeutics for AD are discussed because several metals are found excessively in the AD brain and may play a role in the disease development. Specifically, a novel approach involving the transport of iron chelation agents into and out of the brain by nanoparticles is highlighted. This approach may provide a safer and more effective means of simultaneously reducing several toxic metals in the AD brain. It may also provide insights into the mechanisms of AD pathophysiology, and prove useful in treating other iron-associated neurodegenerative diseases such as Friedreich's ataxia, Parkinson's disease, Huntington's disease, and Hallervorden-Spatz Syndrome. It is important to note that the use of nanoparticle-mediated transport to facilitate toxicant excretion from diseased sites in the body may advance nanoparticle technology, which is currently focused on targeted drug delivery for disease prevention and treatment. The application of nanoparticle-mediated drug transport in the treatment of AD is at its very early stages of development and, therefore, more studies are warranted. Copyright © 2009 American Scientific Publishers. All rights reserved.",Alzheimer disease;Chelation therapy;Metal dysregulation;Nanoparticle delivery;Neurodegeneration;Alzheimer disease/dt [Drug Therapy];blood brain barrier;clinical trial;drug absorption;drug degradation;drug delivery system;drug mechanism;drug structure;drug transport;human;nanotechnology;neurologic disease/si [Side Effect];neurotoxicity/si [Side Effect];nonhuman;review;unspecified side effect/si [Side Effect];Wilson disease;amyloid beta protein/ec [Endogenous Compound];chelating agent/pr [Pharmaceutics];chelating agent/pk [Pharmacokinetics];chelating agent/pd [Pharmacology];clioquinol/dv [Drug Development];clioquinol/dt [Drug Therapy];clioquinol/to [Drug Toxicity];clioquinol/pd [Pharmacology];copper chelating agent/pr [Pharmaceutics];copper chelating agent/pk [Pharmacokinetics];copper chelating agent/pd [Pharmacology];deferasirox/pk [Pharmacokinetics];deferiprone/ae [Adverse Drug Reaction];deferiprone/pk [Pharmacokinetics];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/ct [Clinical Trial];deferoxamine/dt [Drug Therapy];deferoxamine/pr [Pharmaceutics];deferoxamine/pk [Pharmacokinetics];deferoxamine/pd [Pharmacology];deferoxamine/sc [Subcutaneous Drug Administration];edetic acid/ct [Clinical Trial];edetic acid/dt [Drug Therapy];edetic acid/pd [Pharmacology];iron chelating agent/pr [Pharmaceutics];iron chelating agent/pk [Pharmacokinetics];nanoparticle/pr [Pharmaceutics];nanoparticle/pk [Pharmacokinetics];penicillamine/pr [Pharmaceutics];penicillamine/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology];unclassified drug,"Liu, G.;Men, P.;Perry, G.;Smith, M. A.",2009,,http://dx.doi.org/10.1166/jns.2009.005,0,0,
1895,From Wilson's disease to Fabry's disease: Metabolic disorders as diagnosis at a glance. [German],,chelation;conference paper;cornea disease/di [Diagnosis];cornea disease/dt [Drug Therapy];crystal structure;differential diagnosis;gaze;human;keratopathy/dt [Drug Therapy];kidney;liver;metabolic disorder/di [Diagnosis];spleen;symptom;agalsidase alfa/dt [Drug Therapy];amiodarone/dt [Drug Therapy];eye drops/dt [Drug Therapy];mercaptamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Arand, M.",2009,15 Jan,,0,0,
1896,Movement disorders,"This chapter will outline the clinical features, diagnostic and management strategies, and issues relating to transitional care of pediatric-onset movement disorders and will provide insights important for the recognition of adult-onset expression of disorders more typically considered to be of pediatric onset. In addition, recognition of familial risk and the methods for diagnosis of presymptomatic family members will be presented. © 2009, American Academy of Neurology.",allergic rash/si [Side Effect];article;blepharospasm/dt [Drug Therapy];brain depth stimulation;cervical dystonia/dt [Drug Therapy];chorea/di [Diagnosis];chorea/et [Etiology];chorea minor/di [Diagnosis];chorea minor/dt [Drug Therapy];chorea minor/et [Etiology];clinical feature;constipation/si [Side Effect];drug dose titration;dry eye/si [Side Effect];dyskinesia/di [Diagnosis];dyskinesia/dt [Drug Therapy];dyskinesia/et [Etiology];dystonic disorder/di [Diagnosis];dystonic disorder/dt [Drug Therapy];dystonic disorder/et [Etiology];essential tremor;exercise tolerance;focal dystonia/dt [Drug Therapy];generalized dystonia/dt [Drug Therapy];generalized dystonia/th [Therapy];human;Huntington chorea/di [Diagnosis];Huntington chorea/et [Etiology];hypotension/si [Side Effect];motor dysfunction/di [Diagnosis];motor dysfunction/et [Etiology];muscle hypotonia/si [Side Effect];myoclonus/di [Diagnosis];myoclonus/et [Etiology];myoclonus dystonia/di [Diagnosis];myoclonus dystonia/et [Etiology];neuroleptic malignant syndrome/di [Diagnosis];neuroleptic malignant syndrome/et [Etiology];onset age;pantothenate kinase associated neurodegeneration/di [Diagnosis];pantothenate kinase associated neurodegeneration/et [Etiology];parkinsonism/di [Diagnosis];parkinsonism/dt [Drug Therapy];parkinsonism/et [Etiology];personality disorder/si [Side Effect];sedation;side effect/si [Side Effect];spasmodic dysphonia/dt [Drug Therapy];spinocerebellar degeneration/et [Etiology];tic/di [Diagnosis];tremor/di [Diagnosis];tremor/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];xerostomia/si [Side Effect];alprazolam/dt [Drug Therapy];amantadine/dt [Drug Therapy];baclofen/ae [Adverse Drug Reaction];baclofen/do [Drug Dose];baclofen/dt [Drug Therapy];baclofen/tl [Intrathecal Drug Administration];baclofen/po [Oral Drug Administration];beta adrenergic receptor blocking agent/ae [Adverse Drug Reaction];botulinum toxin/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];catechol methyltransferase inhibitor/dt [Drug Therapy];clonazepam/ae [Adverse Drug Reaction];clonazepam/dt [Drug Therapy];entacapone/dt [Drug Therapy];gabapentin/dt [Drug Therapy];gluconate zinc/dt [Drug Therapy];immunoglobulin/dt [Drug Therapy];immunoglobulin/iv [Intravenous Drug Administration];levodopa/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pramipexole/dt [Drug Therapy];prednisone/dt [Drug Therapy];primidone/ae [Adverse Drug Reaction];primidone/dt [Drug Therapy];propranolol;rasagiline/dt [Drug Therapy];ropinirole/dt [Drug Therapy];selegiline/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];tolcapone/dt [Drug Therapy];topiramate/dt [Drug Therapy];trientine/dt [Drug Therapy];trihexyphenidyl/ae [Adverse Drug Reaction];trihexyphenidyl/do [Drug Dose];trihexyphenidyl/dt [Drug Therapy];unindexed drug;zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"T, S. Oman;Lang, A. E.",2009,December,http://dx.doi.org/10.1212/01.CON.0000348883.62435.75,0,0,
1897,Hypoglycemia and endocrine effects of adults' inborn errors of metabolism. [French],"Inborn errors of metabolism (IEM) are rare diseases, most often inherited as an autosomal recessive disorder. They may be associated with endocrine dysfunction, the most frequent of them being disorders of carbohydrate metabolism (hypoglycemia, diabetes). The endocrinologist might be led to screen these complications in a patient whose diagnosis has been done during childhood. In some rare cases, he should evoke the diagnosis in front of an endocrine disorder most often associated to a multisystemic involvement. This spreading field is new, not yet very well known in adulthood. Long-term consequences of IEM on fertility and bone metabolism are still poorly understood. Diagnosis orientation relies on a few specific lab investigations encompassing blood lactate, free fatty acids and 3-hydroxy-butyrate, ammoniemia, carnitine and acylcarnitines, aminoacid and urinary organic chromatography. Hyperinsulinism, glycogenosis, fatty acid s-oxydation, carnitine cycle and glycosylation (CDG syndrome) disorders, fructose intolerance, tyrosinemia, organic aciduria may explain hypoglycemia. These diagnosis should be evoked in front of unexplained adult hypoglycemia. Diabetes is related to iron overload, mitochondriopathy and thiamine sensitive diabetes. Clinical spectrum of some forms of IEM switch from hypoglycemia in childhood to diabetes in adulthood. Mitochondriopathies can be associated to all types of endocrine disorders, the most frequent being diabetes and dysthyroidism. Hypothyroidism is encountered in mitochondriopathies, cystinosis and primary hyperoxaluria. Hypogonadism is almost constant in galactosemia, frequent in CDG syndromes, cystinosis and iron overload. Most of the time, a specialized advice is required, which is one of the mission of reference centres. © 2009 Elsevier Masson SAS. All rights reserved.",Diabetes;Endocrine disorders;Hypoglycemia;Hypogonadism;Hypoparathyroidism;Hypopituitarism;Hypothyroidism;Inborn errors of metabolism;aciduria/dt [Drug Therapy];autosomal recessive disorder;bone metabolism;cerebrovascular accident;chromatography;congenital disorder of glycosylation/cn [Congenital Disorder];congenital disorder of glycosylation/dt [Drug Therapy];cystinosis/dt [Drug Therapy];diabetes mellitus/dt [Drug Therapy];diabetes mellitus/ep [Epidemiology];diabetes mellitus/et [Etiology];disease association;disorders of mitochondrial functions;endocrine disease/co [Complication];endocrine disease/dt [Drug Therapy];Fabry disease;fatty acid oxidation;galactosemia;glycogen synthesis;glycosylation;hemochromatosis;hereditary fructose intolerance/dt [Drug Therapy];human;hyperinsulinism/co [Complication];hyperinsulinism/dt [Drug Therapy];hyperoxaluria;hypoglycemia/co [Complication];hypoglycemia/dt [Drug Therapy];inborn error of metabolism;iron overload;short survey;tyrosinemia;vitamin supplementation;Wilson disease/dt [Drug Therapy];acetylsalicylic acid/dt [Drug Therapy];allopurinol;amino acid/ec [Endogenous Compound];ascorbic acid/dt [Drug Therapy];bicarbonate/dt [Drug Therapy];biotin;carnitine;chlorothiazide/dt [Drug Therapy];diazoxide/dt [Drug Therapy];estrogen/dt [Drug Therapy];glucagon/iv [Intravenous Drug Administration];glucose/dt [Drug Therapy];glucose/iv [Intravenous Drug Administration];glucose/po [Oral Drug Administration];growth hormone/dt [Drug Therapy];indometacin;insulin/dt [Drug Therapy];iron;levothyroxine;mannose/dt [Drug Therapy];mercaptamine;octreotide;penicillamine/dt [Drug Therapy];phenylalanine;propylthiouracil;sulfanilamide;thiamine;trientine/dt [Drug Therapy];tyrosine;ubidecarenone;zinc/dt [Drug Therapy],"Vantyghem, M. C.;Mention, C.;Dobbelaere, D.;Douillard, C.",2009,March,http://dx.doi.org/10.1016/j.ando.2008.12.007,0,0,
1898,Torticollis revealing Wilson's disease. [French],,article;case report;ceruloplasmin blood level;child;clinical assessment;clinical examination;clinical feature;correlation analysis;disease course;focal dystonia/dt [Drug Therapy];focal dystonia/et [Etiology];human;laboratory diagnosis;neuroimaging;radiodiagnosis;school child;torticollis/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Basir, A.;Bougteba, A.;Kissani, N.",2009,April,http://dx.doi.org/10.1016/j.arcped.2008.12.002,0,0,
1899,Evaluation of tetrathiomolybdate in the R6/2 model of Huntington disease,"Huntington disease is an uncommon autosomal dominant neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin protein. The proximate mechanisms responsible for neurodegeneration are unknown. Copper ions may play a role in Huntington disease by promoting oligomerization of expanded polyglutamine repeat protein fragments. Ammonium tetrathiomolybdate is a copper complexing agent with demonstrated tolerability and efficacy in another neurodegenerative disorder, Wilson disease. We evaluated ammonium tetrathiomolybdate in the R6/2 transgenic mouse model of Huntington disease. Ammonium tetrathiomolybdate treatment delayed the onset of motor dysfunction in R6/2 mice. There was a trend towards reduced striatal degeneration, suggesting a neuroprotective effect of ammonium tetrathiomolybdate in this model. Given its known tolerability in humans with neurodegeneration, ammonium tetrathiomolybdate could be considered as a candidate for clinical trials in Huntington disease.",Chelation;Copper;Neurodegeneration;Polyglutamine;Striatum;Tetrathiomolybdate;animal behavior;animal experiment;animal model;animal tissue;article;controlled study;corpus striatum;drug effect;female;Huntington chorea/dt [Drug Therapy];male;motor dysfunction;mouse;mouse strain;nerve degeneration;neuroprotection;nonhuman;oligomerization;outcome assessment;priority journal;rotarod test;transgenic mouse;treatment outcome;copper ion;tetrathiomolybdate ammonium/dv [Drug Development];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/po [Oral Drug Administration];tetrathiomolybdate ammonium/pd [Pharmacology],"Tallaksen-Greene, S. J.;Janiszewska, A.;Benton, K.;Hou, G.;Dick, R.;Brewer, G. J.;Albin, R. L.",2009,06 Mar,http://dx.doi.org/10.1016/j.neulet.2009.01.040,0,0,
1900,Wilson disease as a cause of liver injury in cystic fibrosis,"Cystic fibrosis-related liver disease affects approximately one third of all patients with cystic fibrosis. Initial signs of other liver diseases including the genetically determined disorders of the liver co-inherited with cystic fibrosis may be obscured by or ascribed to cystic fibrosis-related liver disease. We report a patient shown to suffer simultaneously from cystic fibrosis and hepatic Wilson disease. Our case documents that in patients with cystic fibrosis presenting with liver disease, when unusual clinical and/or laboratory abnormalities appear and fail to respond to standard therapy, a second disease, including rare inherited metabolic disorders such as the hepatic form of Wilson disease or alpha<inf>1</inf>-antitrypsin deficiency, should be suspected. © 2008 European Cystic Fibrosis Society.",Cholestasis;Cystic fibrosis;Jaundice;Liver disease;Wilson disease;alpha antitrypsin deficiency;article;case report;Caucasian;cystic fibrosis/dt [Drug Therapy];genetic disorder;Gilbert disease/dt [Drug Therapy];homozygosity;human;human tissue;hyperbilirubinemia/dt [Drug Therapy];ileostomy;liver biopsy;liver injury/dt [Drug Therapy];liver injury/et [Etiology];lung disease;male;meconium ileus/su [Surgery];metabolic disorder;missense mutation;pancreas disease;school child;penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];ursodeoxycholic acid/do [Drug Dose];ursodeoxycholic acid/dt [Drug Therapy],"Kotalova, R.;Jirsa, M.;Vavrova, V.;Vrabelova-Pouchla, S.;Macek Jr, M.",2009,January,http://dx.doi.org/10.1016/j.jcf.2008.09.003,0,0,
1901,Placenta abruption in a woman with Wilson's disease: A case report,"Wilson's disease is a rare genetic disorder of copper metabolism that causes primary hepatic cirrhosis, secondary menstrual abnormalities and infertility. Following the appropriate therapy patients are asymptomatic and pregnancy may be achieved. We present a case of placental abruption in a pregnant woman with Wilson's disease and we review the management dilemmas and treatment options of pregnant women with Wilson's disease. © 2009 licensee BioMed Central Ltd.",abdominal pain;adult;antepartum hemorrhage;Apgar score;article;blood examination;case report;cesarean section;female;fetus malformation;first trimester pregnancy;genetic counseling;gestational age;hospital admission;hospital discharge;human;infant;low drug dose;male;nuchal translucency measurement;outpatient department;peroperative care;postoperative period;pregnant woman;solutio placentae/di [Diagnosis];ultrasound;vitamin supplementation;Wilson disease/dt [Drug Therapy];folic acid;penicillamine/dt [Drug Therapy],"Theodoridis, T. D.;Zepiridis, L.;Athanatos, D.;Dinas, K.;Tzevelekis, F.;Bontis, J. N.",2009,,http://dx.doi.org/10.4076/1757-1626-2-8699,0,0,
1902,Chelation therapy for neurodegenerative diseases,"Mounting evidence suggests a central role for transition biometals in the etiopathogenesis of neurodegenerative diseases (ND). Indeed, while studying the molecular basis for this heterogeneous group of diseases, it has become increasingly evident that biometals and nonphysiological Al are often involved in pathology onset and progression, either by affecting the conformation of specific proteins or by exacerbating local oxidative stress. The apparently critical role played by metal dishomeostasis in ND makes chelation therapy an attractive pharmacological option. However, classical metal chelation approaches, relying on potent metal ligands, turned out to be successful only in those rare cases where exceptional brain metal accumulation occurs due to specific defects in metal metabolism. In contrast, metal-targeted approaches using ligand of intermediate strength seem to be more appropriate in fighting the major ND, although their benefits are still questioned. We report here a survey of recent evidences supporting the use of a variety of metal ligands, and even functionalized nanoparticles, for the treatment of the most common ND. The beneficial neuropharmacological actions of metal-targeted agents most likely arise from local metal redistribution rather than from massive metal removal. The perspectives for the development of new effective agents against ND are critically discussed. © 2009 Wiley Periodicals, Inc.","Aggregation;Amyloid;Chelation;Metal ions;Neurodegeneration;Alzheimer disease/dt [Drug Therapy];amyotrophic lateral sclerosis/dt [Drug Therapy];chelation therapy;clinical trial;degenerative disease;drug effect;drug efficacy;eye toxicity/si [Side Effect];fever/si [Side Effect];homeostasis;human;immunotoxicity/si [Side Effect];injection site reaction/si [Side Effect];lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];neurologic disease/si [Side Effect];neurotoxicity/dt [Drug Therapy];nonhuman;ototoxicity/si [Side Effect];oxidative stress;Parkinson disease/dt [Drug Therapy];prion disease;protein conformation;protein folding;rash/si [Side Effect];retina toxicity/si [Side Effect];review;thalassemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];2 methyl 5 (3,4,5 trimethoxybenzamido)decahydroisoquinoline/dv [Drug Development];alpha synuclein/ec [Endogenous Compound];aluminum/ec [Endogenous Compound];amyloid beta protein/ec [Endogenous Compound];beta lactam antibiotic;chelating agent/an [Drug Analysis];chelating agent/pr [Pharmaceutics];clioquinol/ct [Clinical Trial];clioquinol/dv [Drug Development];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];copper ion/ec [Endogenous Compound];deferiprone/ae [Adverse Drug Reaction];deferiprone/an [Drug Analysis];deferiprone/dt [Drug Therapy];deferiprone/po [Oral Drug Administration];donepezil/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];dp 109/an [Drug Analysis];dp 109/dv [Drug Development];dp 109/dt [Drug Therapy];dp 109/po [Oral Drug Administration];entacapone/dt [Drug Therapy];feralex/an [Drug Analysis];feralex/dv [Drug Development];iron/ec [Endogenous Compound];levodopa/dt [Drug Therapy];manganese/ec [Endogenous Compound];memantine/dt [Drug Therapy];metal ion/to [Drug Toxicity];monoamine oxidase B inhibitor/dt [Drug Therapy];nanoparticle;penicillamine/ae [Adverse Drug Reaction];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];rasagiline/dt [Drug Therapy];rivastigmine/dt [Drug Therapy];selegiline/dt [Drug Therapy];tacrine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];unclassified drug;unindexed drug;vk 28/an [Drug Analysis];vk 28/dv [Drug Development];vk 28/dt [Drug Therapy];vk 28/to [Drug Toxicity];vk 28/ip [Intraperitoneal Drug Administration];vk 28/po [Oral Drug Administration];zinc ion/ec [Endogenous Compound]","Bolognin, S.;Drago, D.;Messori, L.;Zatta, P.",2009,July,http://dx.doi.org/10.1002/med.20148,0,0,
1903,Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients,"Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13-26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. Themedian follow-up was 14 years (range 2-30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 +/- 38 versus 91 +/- 23 +/- mug: P = 0.01) and serum non-ceruloplasmin-bound copper concentrations (11 +/- 2 versus 7 = 1 mug/dL: P = 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group. Conclusion: The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering. Copyright © 2009 by the American Association for the Study of Liver Diseases.",adolescent;adult;article;bilirubin blood level;clinical article;controlled study;copper blood level;decompensated liver cirrhosis;deterioration;drug efficacy;drug substitution;drug withdrawal;female;gastrointestinal symptom/si [Side Effect];granulocytopenia/si [Side Effect];human;human tissue;liver cirrhosis;long term care;macrocytic anemia/si [Side Effect];male;monotherapy;priority journal;treatment response;Wilson disease/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];copper;gluconate zinc/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy],"Linn, F. H. H.;Houwen, R. H. J.;Van Hattum, J.;Van Der Kleij, S.;Van Erpecum, K. J.",2009,,http://dx.doi.org/10.1002/hep.23182,0,0,
1904,Analysis of multiple elements in urine of patients with Wilson's disease during penicillamine therapy. [Chinese],"Objective: To analyse the concentrations of 21 elements in 24 h urine of patients with Wilson's disease (WD) during penicillamine therapy. Methods: Forty patients with WD undergoing penicillamine therapy and hypo-copper diets were collected (WD group), and another 12 healthy people were served as control group. The concentrations of 21 elements of Cr, Fe, Co, Se, Mn, Cu, Zn, As, Be, Al, V, Ni, Cd, Sb, Ba, Pb, Ti, Th, U, Ca and Mg in 24 h urine were determined by inductively coupled plasma mass spectrometry. Results: For 7 essential trace elements (Cr, Fe, Co, Se, Mn, Cu and Zn), the concentrations of Mn, Cu and Zn in 24 h urine of WD group were significantly higher than those in control group (P < 0.05, P < 0.01 and P < 0.01). For 12 unessential trace elements (As, Be, Al, V, Ni, Cd, Sb, Ba, Pb, Ti, Th and U), the concentration of As in 24 h urine of WD group was significantly higher than that in control group (P < 0.05). For 2 macroelements (Ca and Mg), the concentration of Ca in 24 h urine of WD group was significantly higher than that in control group (P < 0.001). Conclusion: For patients with WD undergoing penicillamine therapy and hypocopper diets, the concentration of Cu in 24 h urine increases, and those of Mn, Zn, As and Ca also change.",Element analysis;Penicillamine;Urine;Wilson's disease;article;clinical article;controlled study;human;mass spectrometry;urinalysis;Wilson disease/dt [Drug Therapy];aluminum;antimony;arsenic;barium;beryllium;cadmium;calcium;chromium;cobalt;copper;iron;lead;magnesium;manganese;nickel;penicillamine/dt [Drug Therapy];selenium;thorium;titanium;uranium;vanadium;zinc,"Jiao, X. T.;Liu, X. Q.;Huang, L. S.;Yu, X. G.;Yan, C. H.;Xu, X. X.;Gu, X. F.",2009,,,0,0,
1905,Chiral toxicology: It's the same thing only different,"Chiral substances possess a unique architecture such that, despite sharing identical molecular formulas, atom-to-atom linkages, and bonding distances, they cannot be superimposed. Thus, in the environment of living systems, where specific structure-activity relationships may be required for effect (e.g., enzymes, receptors, transporters, and DNA), the physiochemical and biochemical properties of racemic mixtures and individual stereoisomers can differ significantly. In drug development, enantiomeric selection to maximize clinical effects or mitigate drug toxicity has yielded both success and failure. Further complicating genetic polymorphisms in drug disposition, stereoselective metabolism of chiral compounds can additionally influence pharmacokinetics, pharmacodynamics, and toxicity. Optically pure pharmaceuticals may undergo racemization in vivo , negating single enantiomer benefits or inducing unexpected effects. Appropriate chiral antidotes must be selected for therapeutic benefit and to minimize adverse events. Enantiomers may possess different carcinogenicity and teratogenicity. Environmental toxicology provides several examples in which compound bioaccumulation, persistence, and toxicity show chiral dependence. In forensic toxicology, chiral analysis has been applied to illicit drug preparations and biological specimens, with the potential to assist in determination of cause of death and aid in the correct interpretation of substance abuse and ""doping"" screens. Adrenergic agonists and antagonist, nonsteroidal anti-inflammatory agents, SSRIs, opioids, warfarin, valproate, thalidomide, retinoic acid, N-acetylcysteine, carnitine, penicillamine, leucovorin, glucarpidase, pesticides, polychlorinated biphenyls, phenylethylamines, and additional compounds will be discussed to illustrate important concepts in ""chiral toxicology."" © The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.",Antidotes;Chiral;Ecotoxicology;Forensic toxicology;Stereoisomer;Teratology;acne conglobata/dt [Drug Therapy];acne cystica/dt [Drug Therapy];Alzheimer disease/dt [Drug Therapy];bioequivalence;bleeding/si [Side Effect];bronchodilatation;carcinogenicity;cardiomyopathy/dt [Drug Therapy];cardiotoxicity/dt [Drug Therapy];chirality;cis trans isomerism;clinical trial;contrast induced nephropathy/dt [Drug Therapy];diastereoisomer;drug absorption;drug bioavailability;drug cytotoxicity/dt [Drug Therapy];drug design;drug DNA binding;drug dosage form comparison;drug elimination;drug half life;drug intoxication/dt [Drug Therapy];drug metabolism;drug protein binding;drug receptor binding;enantiomer;heart arrhythmia/si [Side Effect];heart protection;heavy metal poisoning/dt [Drug Therapy];human;hyperglycemia/si [Side Effect];hyperkalemia/si [Side Effect];hypoglycemia/dt [Drug Therapy];hyponatremia/si [Side Effect];isomer;Kaposi sarcoma/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];leukopenia/si [Side Effect];liver toxicity/dt [Drug Therapy];low drug dose;mercurialism/dt [Drug Therapy];mitochondrial toxicity/dt [Drug Therapy];mutagenicity;myasthenia gravis/dt [Drug Therapy];myasthenia like syndrome/si [Side Effect];nonhuman;protein expression;pulmonary hypertension/si [Side Effect];QT prolongation/si [Side Effect];reproductive toxicity;restless legs syndrome/si [Side Effect];review;serotonin syndrome/si [Side Effect];stereochemistry;stereoisomerism;structure activity relation;structure analysis;tachycardia/si [Side Effect];thrombocytopenia/si [Side Effect];thrombosis/si [Side Effect];torsade des pointes/si [Side Effect];valvular heart disease/si [Side Effect];Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];acetylcysteine/to [Drug Toxicity];alitretinoin/an [Drug Analysis];alitretinoin/dt [Drug Therapy];alitretinoin/to [Drug Toxicity];alitretinoin/tp [Topical Drug Administration];benzphetamine/to [Drug Toxicity];carboxypeptidase G2/cm [Drug Comparison];carboxypeptidase G2/dt [Drug Therapy];carnitine/ae [Adverse Drug Reaction];carnitine/dt [Drug Therapy];citalopram/ae [Adverse Drug Reaction];citalopram/ct [Clinical Trial];citalopram/an [Drug Analysis];citalopram/to [Drug Toxicity];citalopram/pk [Pharmacokinetics];citalopram/pd [Pharmacology];dexfenfluramine/ae [Adverse Drug Reaction];dexfenfluramine/an [Drug Analysis];dexfenfluramine/to [Drug Toxicity];dexfenfluramine/pk [Pharmacokinetics];dexfenfluramine/pd [Pharmacology];dibenzofuran derivative/to [Drug Toxicity];dioxin/to [Drug Toxicity];escitalopram/ae [Adverse Drug Reaction];escitalopram/ct [Clinical Trial];escitalopram/an [Drug Analysis];escitalopram/to [Drug Toxicity];escitalopram/pk [Pharmacokinetics];escitalopram/pd [Pharmacology];fipronil/to [Drug Toxicity];folinic acid/cm [Drug Comparison];folinic acid/dt [Drug Therapy];folinic acid/iv [Intravenous Drug Administration];folinic acid/po [Oral Drug Administration];folinic acid/pk [Pharmacokinetics];glucose/dt [Drug Therapy];glucose/pk [Pharmacokinetics];isotretinoin/an [Drug Analysis];isotretinoin/dt [Drug Therapy];isotretinoin/to [Drug Toxicity];isotretinoin/po [Oral Drug Administration];levalbuterol/ae [Adverse Drug Reaction];levalbuterol/an [Drug Analysis];levalbuterol/to [Drug Toxicity];levalbuterol/pk [Pharmacokinetics];levalbuterol/pd [Pharmacology];methadone/ae [Adverse Drug Reaction];methadone/an [Drug Analysis];methadone/to [Drug Toxicity];methadone/pk [Pharmacokinetics];methadone/pd [Pharmacology];nitrosonornicotine/to [Drug Toxicity];organochlorine derivative/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];physostigmine/dv [Drug Development];physostigmine/do [Drug Dose];physostigmine/dt [Drug Therapy];placebo;polychlorinated biphenyl derivative/to [Drug Toxicity];pyrethroid/to [Drug Toxicity];razoxane/dt [Drug Therapy];razoxane/pd [Pharmacology];retinoic acid/ad [Drug Administration];retinoic acid/an [Drug Analysis];retinoic acid/do [Drug Dose];retinoic acid/to [Drug Toxicity];retinoic acid/po [Oral Drug Administration];retinoic acid/tp [Topical Drug Administration];salbutamol/ae [Adverse Drug Reaction];salbutamol/an [Drug Analysis];salbutamol/to [Drug Toxicity];salbutamol/pk [Pharmacokinetics];salbutamol/pd [Pharmacology];thalidomide/an [Drug Analysis];thalidomide/to [Drug Toxicity];thalidomide/iv [Intravenous Drug Administration];thalidomide/po [Oral Drug Administration];unindexed drug;valproic acid/to [Drug Toxicity];warfarin/ae [Adverse Drug Reaction];warfarin/an [Drug Analysis];warfarin/to [Drug Toxicity];warfarin/pk [Pharmacokinetics];warfarin/pd [Pharmacology],"Smith, S. W.",2009,,http://dx.doi.org/10.1093/toxsci/kfp097,0,0,
1906,Dermatological signs in Wilson's disease,"Background: Because no data on skin and mucosal findings of patients with Wilson's disease have been published so far, the aim of the present study was to investigate the prevalence of mucosal and skin findings in childhood Wilson's disease and to determine its specific dermatological findings, if any exist. Methods: Thirty-seven 4-17-year-old children with Wilson's disease were included. A complete skin, scalp skin, mucous membrane and nail examination was performed. Results: Of the children, 26 (70.3%) had at least one dermatological finding. Twenty-five (67.6%), five (13.5%), nine (24.3%) had at least one skin, mucosal and nail finding, respectively. The most prevalent dermatological diagnosis of the Wilson's disease patients was xerosis (45.7%). The presence of dermatological findings was not related to drug usage, severity of the disease, or malnutrition. The duration of the disease was not different in patients with or without dermatological findings. The frequency of skin findings alone, however, was high in relatively newly diagnosed patients (<2 years). Conclusion Dermatologist should be aware of the various dermatological manifestations of Wilson's disease, because a careful and objective skin, mucosa, nail and hair examination may be indicative of a diagnosis of Wilson's disease, particularly in early cases. © 2008 Japan Pediatric Society.",Children;Mucosa;Nail;Skin;Wilson's disease;adolescent;angioma;article;ascites;candidiasis;cheilitis;child;cholestasis;clinical article;clubbing fingers;dandruff;disease severity;drug use;erythema;female;frequency analysis;hematoma;hepatomegaly;herpes simplex;human;human tissue;hyperhidrosis;hypertrichosis;jaundice;keratosis;male;malnutrition;nail dystrophy;nail pigmentation;neurologic disease;papular rash;pityriasis;portal hypertension;preschool child;prevalence;priority journal;pustule;scalp;scanty hair;school child;skin atrophy;skin manifestation/di [Diagnosis];skin manifestation/ep [Epidemiology];skin pigmentation;splenomegaly;tinea versicolor;verruca vulgaris;vitiligo;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];xerosis/di [Diagnosis];xerosis/ep [Epidemiology];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Seyhan, M.;Erdem, T.;Selimoglu, M. A.;Ertekin, V.",2009,June,http://dx.doi.org/10.1111/j.1442-200X.2008.02766.x,0,0,
1907,Copper in Alzheimer's disease: too much or too little?,"A considerable amount of literature has accrued examining the role of copper in the pathogenesis of Alzheimer's disease. Remarkably, there is in vitro and animal data to support both copper toxicity and copper deficiency as relevant mechanisms in Alzheimer's disease. These data have prompted preliminary clinical trials of both copper complexing therAbetay and copper supplementation therAbetay, which have yielded mixed results. The preclinical and clinical studies are discussed here in an effort to determine how to move forward with rational clinical trials focused on copper modulation. © 2009 Expert Reviews Ltd.",Alzheimer's disease;Animal model;Chelation;Clinical trial;Copper;Oxidative damage;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];Alzheimer disease/pc [Prevention];central nervous system;copper deficiency;drug dose titration;dystonia;human;motor dysfunction;nonhuman;review;spinal cord disease;Wilson disease/dt [Drug Therapy];amyloid beta protein/ec [Endogenous Compound];amyloid precursor protein/ec [Endogenous Compound];chelating agent/ct [Clinical Trial];clioquinol/ct [Clinical Trial];clioquinol/dt [Drug Therapy];clioquinol/pd [Pharmacology];copper/ct [Clinical Trial];copper/dt [Drug Therapy];PBT2/ct [Clinical Trial];PBT2/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc acetate/dt [Drug Therapy],"Quinn, J. F.;Crane, S.;Harris, C.;Wadsworth, T. L.",2009,May,http://dx.doi.org/10.1586/ern.09.27,0,0,
1908,Wilson's disease: Experience with 71 patients followed for two decades in a Tertiary Centre in Saudi Arabia,"Background: Wilson's disease (WD) is a rare, but treatable condition that often presents diagnostic dilemmas. Aims: This study presents King Faisal Specialist Hospital & Research Centre (a tertiary care centre in Riyadh, Saudi Arabia) experience over two decades with patients with WD in order to illustrate the diverse patterns, therepies, and outcomes. Patients & Methods: Clinical and laboratory findings of 71 patients with WD; Mean+/-SD age at presentation was 16.8+/-10.7 (Range: 2-49) years; 40(56.3%) were males; referred to our centre were reviewed and analyzed. Results: The main manifestations of WD were hepatic, neurological, and mixed in 39(54.9%), 14(19.7%), and 18(25.4%) patients respectively, and 11(15.5%) of them were asymptomatic cases detected by family screening. Family history of WD was positive in 41(57.7%) patients, and consanguinity of parents was in 26(36.6%) patients. Kayser Fleiser Ring (KFR) was absent, questionable, and present in 32(45.1%), 3(4.2%), and 36(50.7%) respectively. KFR was positive in 10(71.4%), 11(28.2%), and 15(83.3%) of the patients who had neuological, hepatic, and mixed pictures respectively. The mean follow up period of 92.2+/-72.9 (range: 1-320) month. The mean age at the end of follow up was 25.3+/-12 (Range: 4-62) years. Hepatoma was discovered in 5(7%) patients. Penicillamine therapy was used by 58(81.7%) patients, while zinc and trientin were given to 32(45.1) and 11(15.5%) patients respectively. Sixteen (22.5%) patients underwent liver transplantation. and one died (1.4%) on the waiting list. Ten (14.1%) patients died during follow up, while 45(63.4) and 16(22.5%) are still on- or lost from-follow up respectively. The liver condition remained stable or improved in 35(49.3%), and the neurological status showed improvement in 11(34.4%) out of the 32 patients who had neurological involvement. Conclusions: This is the biggest cohort to be reported from the Middle East. WD presentation and outcome of WD are very diverse. Diagnosis of WD still depends mainly on clinical, radiological, and laboratory evidence of abnormal copper metabolism. WD should be considered in patients of any age with obscure hepatic and/or neurological abnormalities.",patient;Saudi Arabia;gastrointestinal disease;follow up;laboratory;diagnosis;Tertiary (period);liver;Middle East;copper metabolism;medical specialist;hospital;tertiary health care;male;screening;parent;liver cell carcinoma;family history;therapy;liver transplantation;hospital admission;consanguinity;penicillamine;zinc,"Fadda, M. A.;Helmy, A.;Benmousa, A. H.;Al-Kahtani, K. M.;Al-Ashgar, H. I.;M.N, A. LQuaiz;Abdulla, M.;Alsohaibani, F. I.;Kagevi, I.",2009,May,http://dx.doi.org/10.1016/S0016-5085%2809%2963888-9,0,1,
1909,Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients,"Although zinc inhibits intestinal copper absorption in Wilson disease, its use as exclusive therapy is controversial, particularly in symptomatic pts. We treated 17 symptomatic Wilson pts with zinc only. Presentation was exclusive hepatic, exclusive neurologic and combined in 7, 5 and 5 pts resp. Median follow-up was 14 yrs (range 2-30). Hepatic disease was classified as: decompensated cirrhosis (Child-Pugh B/C), compensated cirrhosis (Child-Pugh A), moderate (abnormal liver biochemistry and radiology, no cirrhosis) or minor (only abnormal liver biochemistry). Mean elemental zinc dose was 147 +/- 12 mg/day (range 67 -270) at start and 199 +/- 20 mg/day (90 - 360) at end of follow up (P=0.03), without differences between various presentation modes. Side effects were rare, except gastrointestinal complaints. One pt on concomitant anti-epileptics experienced reversible agranulocytosis. Of 12 pts with initial hepatic disease, 2 had decompensated cirrhosis at baseline and both improved to compensated state after initiation of zinc. Two of 5 pts with initial compensated cirrhosis progressed to decompensated state after 16 resp. 18 yrs, and 3 remain stable. Three of 5 pts with moderate or mild liver disease remain stable and 2 improved. Two of 5 pts with exclusive neurological presentation at baseline developed moderate liver disease resp. compensated cirrhosis after 4 resp. 5 yrs treatment. In the hepatic group, apart from improved bilirubin levels, no significant changes occurred in liver biochemistry or function. Neurologic symptoms improved markedly in 9 of 10 pts in the neurologic group, and deteriorated in 1 pt. MRI brain improved in 4, remained stable in 4 and deteriorated in 2 cases. Elevated serum free copper levels normalized (<0.15 mg/L) within one yr zinc in 15/17 pts, without difference between hepatic or neurologic pts. In contrast, adequate 24-hr urinary copper excretion was obtained more often in neurologic than hepatic pts (<100 ug/24 hrs at end of follow up in 5/5 exclusive neurologic pts, 2/5 pts with combined presentation but only 1/7 pts with exclusive hepatic presentation). 24 hr urinary copper excretion (mean+/-SEM) in neurologic vs exclusive hepatic pts was 494+/-167 vs 1149+/-798 (median 390 vs 405) at baseline, 157+/-29 vs 256+/-46 after 1 yr and and 100+/-25 vs 225+/- 37 mug/24 hrs (P<0.01) at end of follow up. Conclusions: Outcome of exclusive zinc therapy is generally satisfactory in case of neurologic disease. Although even decompensated cirrhosis may improve markedly under this treatment modality, liver disease may also worsen, possibly related to less efficient decoppering in hepatic pts.",gastrointestinal disease;patient;Wilson disease;monotherapy;liver disease;liver cirrhosis;follow up;decompensated liver cirrhosis;liver;neurologic disease;therapy;child;excretion;absorption;radiology;gastrointestinal symptom;epilepsy;agranulocytosis;brain;serum;side effect;nuclear magnetic resonance imaging;zinc;copper;bilirubin,"Linn, F.;Houwen, R.;Van Hattum, J.;Van Erpecum, K. J.",2009,May,http://dx.doi.org/10.1016/S0016-5085%2809%2963887-7,0,0,
1910,Role of ammonium tetrathiomolybdate and copper in cancer: Effect on COX-2 pathway,"Background & Aim: Copper is a trace element that has been linked to cancer for several years; however, its exact role in cancer is still controversial. Ammonium Tetrathiomolybdate (TM) is a drug that was developed for the treatment of Wilson's disease and nowadays it is under study as it seems to have an important effect on cancer. So far, due to clinical studies and animal models, it is known that TM down regulates VEGF, IL-1alpha and IL-8, but few have been done In Vitro to try to clarify its effects and mechanism(s) of action. In this study we determined the effects of TM and copper on the known cancer-related Cyclooxygenase-2 (COX-2) pathway. Methods: The gastric adenocarcinoma cell line MKN45 and the esophageal squamous cell carcinoma TTn; which correspond to two major causes of death by cancer in the world, were used in this study. These cells were treated with TM and copper, assessing their viability and chemo-sensitivity with the non-radioactive MTS/PMS method. COX-2 mRNA expression was assessed by RT and Real Time PCR and protein expression was assessed by Western Blot. PGE2 was assessed by ELISA. Results & Discussion: Increasing concentrations of copper reduced cell viability in a dose dependant manner, which is translated as stress and eventually toxicity to the cells. Concomitantly, there was an increase in COX-2 pathway which was determined by increase of COX-2 mRNA (up to 4.5 fold) and protein (up to 2.5 fold), followed by increase of PGE<inf>2</inf>. For the first time, we show that high concentrations of TM cause no toxicity on cell lines different to breast cancer. As well, TM down regulated importantly the COX-2 pathway in TTn. Despite copper and TM's opposite effects on COX-2, treatment with both of them showed higher up regulation of COX-2 than that caused by copper alone. Conclusions: Excess copper might have a role (besides its need for angiogenesis) in cancer since it induces stress, toxicity and up regulates COX-2 pathway. Here we describe that TM is not toxic In Vitro, just as it has been previously described In Vivo . TM is able to down regulate COX-2 pathway under usual cell culture conditions; however, TM was not able to decrease COX-2 up regulation caused by excess copper. This leads us to believe that a)TM could be useful in the treatment of certain gastrointestinal cancers, b)TM seems to have a biochemical mechanism different to simple copper chelation, and c)this mechanism is probably inhibited by excess copper binding the TM, making it unavailable and becoming biologically inactive.",neoplasm;gastrointestinal disease;toxicity;cell line;in vitro study;upregulation;cell culture;digestive system cancer;chelation;clinical study;animal model;Wilson disease;enzyme linked immunosorbent assay;stomach adenocarcinoma;esophageal squamous cell carcinoma;death;real time polymerase chain reaction;protein expression;Western blotting;cell viability;breast cancer;angiogenesis;copper;tetrathiomolybdate ammonium;messenger RNA;prostaglandin E2;trace element;interleukin 1;interleukin 8;cyclooxygenase 2;protein;vasculotropin,"Sanchez-Siles, A. A.;Ishimura, N.;Rumi, M. A.;Ishihara, S.;Kinoshita, Y.",2009,May,http://dx.doi.org/10.1016/S0016-5085%2809%2963504-6,0,0,
1911,Comparative study of morning urine copper to zinc ratio and 24 h urinary copper excretion for the diagnosis of Wilson's disease in children,"Background and Aims: Although 24-hour urinary copper excretion is valuable for diagnosis of Wilson's disease, accurate, timed collection entails practical difficulties. This study aimed to compare the diagnostic value of morning urine copper to zinc (Copper/Zinc) ratio and 24-hour urinary copper excretion in Wilson's disease (WD) children. Methods: From July 2005 to June 2007, morning urine and 24-hour urine were collected from 96 patients who were hospitalized for investigating liver disease in a tertiary pediatric hospital. Each patient was re-evaluated according to WD Scoring system, and was assigned to one of the three groups, WD, suspecting WD, and non-WD. 24, 6, and 64 cases were thus assigned to each group respectively. Urine copper and zinc concentration was determined simultaneously by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: The morning urine copper/zinc ratio and 24-hour urinary copper excretion correlated well (r=0.758, P<0.001). The morning urine copper/zinc ratio was significantly higher in WD group than that in the non-WD group (median 0.370 vs 0.051, Z-value -6.502, P= 0.000), as well was the 24-hour copper excretion (median 87.1 vs 24.2, Z-value -6.208, P= 0.000). The area under ROC curve is comparable between morning urine copper/zinc ratio and 24-hour urinary copper excretion (0.953 vs. 0.934). By using a cutoff value of 0.17, the sensitivity and specificity of morning urine copper/zinc ratio were 86.4% and 92.2%; by a cutoff value of 50.8ug, the sensitivity and specificity of 24 h copper excretion were 90.9% and 93.7% respectively. Conclusions: Morning urine Copper/Zinc ratio could be used as a good replacement of 24hr urinary copper excretion for diagnosing WD.",Wilson disease;diagnosis;excretion;urine;liver;comparative study;child;sensitivity and specificity;patient;diagnostic value;liver disease;pediatric hospital;scoring system;mass spectrometry;receiver operating characteristic;copper;zinc,"Lu, Y.;Wang, J. S.;Wang, X. H.;Zhu, Q. R.",2009,April,,0,0,
1912,Comparison of the urinary copper/zinc ratio to 24-hour urinary copper excretion for diagnosis of Wilson's disease in children: A prospective study,"Background: Although 24h urinary copper excretion is valuable for diagnosis of Wilson's disease (WD), accurate, timed collection entails practical difficulties. In a preliminary study, we found that morning urinary copper/zinc (Cu/Zn) ratio seems a promising replacement parameter. This study aims to compare its diagnostic value to 24 hour urinary copper excretion for WD in children presented with liver manifestations. Methods: From July 2005 to June 2007, 24h urine and morning urine sample were collected from consecutive liver patients over three years old admitted to our unit. Each patient was scored by WD scoring system involving clinical data and routine laboratory results by two pediatricians independently. ATP7B gene was sequenced in patients who had acute liver failure or a WD score between 2 and 3 and therefore each child was assigned to WD or non-WD group. Copper and zinc concentration was determined with Inductively Coupled Plasma Mass Spectrometry by a technician without knowledge of clinical diagnosis. SPSS was used for data analysis. Results: 94 patients including 26 WD cases and 68 non-WD cases, of whom both morning urine sample and 24h urine sample were correctly collected, were enrolled. 14 of them were grouped by combining the clinical data and genetic study. The morning urinary Cu/Zn ratio and 24h urinary copper excretion correlated well (r=0.758, P=0.000). The morning urine Cu/Zn ratio was significantly higher in WD group (median 0.37, range 0.07-12.74) than that in non-WD group (median 0.05, range 0.01-1.23, Z=-6.502, P=0.000); so were the 24h Cu/Zn ratio (WD group, median 0.39, range 0.04-10.7; non-WD group, median 0.06, range 0.00-0.45; Z=-6.020, P=0.000) and 24h urinary copper excretion (WD group, median 87.1ug, range 18.3-1180.5ug; non-WD group, median 24.2ug, range 1.4-357.9ug; Z=-6.208, P=0.000). There was no significant difference of 24h zinc excretion between two groups (WD group, median 399ug, range 17-1641ug; non-WD group, median 359ug, range 6.4-7287ug; Z=-2.100, P=0.834). The area under ROC curve was comparable among morning urine Cu/Zn ratio, 24h urine Cu/Zn ratio and 24h copper excretion, with median and 95% CI 0.953 (0.909-0.998), 0.977 (0.834-0.897) and 0.934 (0.867-1.000) respectively. The sensitivity, specificity, positive predictive value and negative predictive value of morning urine Cu/Zn ratio were 90.9%, 79.7%, 62.9% and 96.2% by a cutoff value of 0.1, and 81.8%, 95.3%, 87% and 93.8% by a cutoff of 0.2 respectively. Conclusions: Morning urinary Cu/Zn ratio is a promising parameter for replacement of 24-hour urinary copper excretion for diagnosis of WD in children.",excretion;Wilson disease;prospective study;child;diagnosis;liver;liver disease;urine;patient;urinalysis;clinical study;liver failure;mass spectrometry;data analysis;zinc urine level;receiver operating characteristic;diagnostic value;scoring system;laboratory;pediatrician;gene;copper;zinc,"Wang, J. S.",2009,,http://dx.doi.org/10.1002/hep.23301,0,0,
1913,The diagnostic value of morning urine copper to zinc ratio in Wilson's disease children,"Objectives: To compare the diagnostic value of morning urine copper to zinc (Copper/Zinc) ratio and 24 hour urinary copper excretion in Wilson's disease (WD) children. Methods: Morning urine and 24 hour urine were collected from 96 patients over three years age who were hospitalized in a tertiary pediatric liver service. Each patient was re-evaluated according to WD Scoring system, and was assigned to one of the three groups: WD, suspecting WD, and non-WD. 24, 6, and 64 cases were assigned to WD, suspecting WD, and non-WD respectively. Urine copper and zinc concentration was determined simultaneously by using Inductively Coupled Plasma Mass Spectrometry. Results: The morning urine copper/zinc ratio and 24hr urinary copper excretion correlated well (r=0.758, P < 0.001). The median of morning urine copper/zinc ratio, 24hr urine copper/zinc ratio, 24h copper excretion, and 24h zinc urinary excretion were 0.370, 0.394, 87.1 and 398.7 in WD group, and 0.051, 0.061, 24.2 and 358.9 in the non-WD group respectively. The differences of morning urine copper/zinc ratio, 24hr urine copper/zinc ratio, and 24h copper excretion were significant (Z-value -6.502, -6.020 and -6.208 respectively, all P values < 0.000). By using cutoff values of 0.17, 50.8, and 0.12 for morning urine copper/zinc ratio, 24hr urine copper/zinc ratio, 24h copper excretion, the sensitivity and specificity were 86.4% and 92.2%, 90.9% and 93.7%, and 86.4% and 85.9% respectively. Conclusion: Morning urine Copper/Zinc ratio could be used as a good replacement of 24hr urinary copper excretion for diagnosing WD.",urine;child;Wilson disease;diagnostic value;liver;Asian;excretion;patient;scoring system;mass spectrometry;urinary excretion;statistical significance;sensitivity and specificity;copper;zinc,"Lu, Y.;Liu, X. Q.;Wang, X. H.;Wang, J. S.",2009,,http://dx.doi.org/10.1007/s12072-009-9123-4,0,0,
1914,Re-evaluation of the diagnostic criteria for Wilson disease in a cohort of predominantly asymptomatic children,"Wilson's disease (WD) is a challenging diagnosis, especially in children. A prompt diagnosis is needed in order to avoid disease progression. AIM: To re-evaluate the conventional diagnostic criteria and the Ferenci diagnostic score [1] in children with WD. Patients and methods: We retrospectively evaluated 43 children with WD (28 boys, median age 6.1 years, range 1.1-20.9) and 58 with liver disease other than WD (36 boys, median age 7.1 years, range 2-16). Among WD children, 35 (81%) were asymptomatic (30 with isolated hypertransaminasemia, 5 picked up by familial screening). Cupruria was evaluated before (basal cupruria [BCu]) and after (penicillamine challenge test cupruria [PCTCu]) penicillamine 500 mg orally 12 hourly x 2. Results: Ceruloplasmin, BCu and PCTCu significantly differed between WD and controls (P<0.0001, P<0.0001 and P<0.03, respectively). ROC analysis for ceruloplasmin at cut-off of <=20 mg/dl showed sensitivity of 95.4% (95% confidence interval [CI], 84.5-99.4%) and specificity of 84.4% (95% CI, 72.5-92.6%).With a cut-off of<=10mg/dl, sensitivity and specificity were 65.9% (95% CI, 50-79.5%) and 96.5% (95% CI, 88-99.6%), respectively. A BCu threshold of >=100 mug/24h showed sensitivity of 65.8% (95% CI, 49.4-79.9%) and specificity of 98.2% (95% CI, 90.7-99.9%), whereas at >=40 mug/24h sensitivity was 78% (95% CI, 62.4-89.4%) and specificity 87.9% (95% CI, 76.7-95%). ROC area for PCTCu was not significant (AUC 0.63, P=0.051), and in our cohort this test showed sensitivity of only 15.4% (95% CI, 4.3-34.8%) and specificity of 94.8% (95% CI, 85.6-98.9%). Finally, we assessed the diagnostic accuracy of the Ferenci score [1]: at the proposed score of >=4, sensitivity was 96.7% (95% CI, 83.3-99.9%) and specificity 93.3% (95% CI, 77.9-99.1%), with a ROC area of 0.95, P<0.0001. Conclusions: Diagnostic accuracy of ceruloplasmin and BCu, considered as single tests, are high in a cohort of predominantly asymptomatic children with WD.We have observed optimal sensitivity and specificity for BCu with a cut-off value of >=40 mug/24h as recommended by recent guidelines. Instead, we do not recommend to measure PCTCu routinely in asymptomatic children because of its low sensitivity. Our observations confirm that WD diagnosis is multi-step, as pointed out by high accuracy of the diagnostic scoring system.",diagnosis;child;Wilson disease;boy;sensitivity and specificity;diagnostic accuracy;scoring system;area under the curve;provocation test;patient;liver disease;hypertransaminasemia;disease course;screening;confidence interval;receiver operating characteristic;ceruloplasmin;penicillamine,"Nicastro, E.;Ranucci, G.;Cirillo, F.;Vegnente, A.;Vajro, P.;Iorio, R.",2009,,http://dx.doi.org/10.1016/S1590-8658%2809%2960497-7,0,0,
1915,An adolescent suffering from Wilson disease: Presentation with haemolytic anaemia and good response with zinc acetate monotherapy,"A previously healthy 17-year-old female was seen in a local hospital because of ingravescent jaundice. She presented with decrease in Hb values (to 5.4 g/dL), bilirubin values of 10.2 mg/dl (direct 2.9 mg/dl), thrombocytopenia (125.000/mm<sup>3</sup>), increased INR 1.64 (0.7-1.1), decreased ATIII, AST/ALT 92/38 U/L, albumin 2.5 g/dL. Direct and indirect Coombs' tests were negative and fragmented red cells were found on peripheral blood film. She was treated with transfusions. On admission on our Institute, the girl presented moderate hepatomegaly and splenomegaly. Microangiopathic haemolytic anaemia was confirmed: coagulation screening revealed PT ratio 1.63 (0.84-1.16) and PTT ratio 1.44 (0.80-1.21), as well as decreased coagulation factors (II, V, VII, X) and antithrombin consistent with liver disease. Infectious diseases were excluded and autoimmunity tests were negative. Abdominal ultrasound showed increased liver volume with non-homogeneous echostructure. Cupraemia was 107 mug/dL (85-165), ceruloplasmin was 9.2 mg% (18-70) and Kayser-Fleischer ring was present at 360degree. The suspicion of WD was confirmed by diagnostic scoring system of Ferenci [1], that with a score of 5 suggested WD as highly probable. Liver biopsy was not performed due to coagulation values. The patient received treatment with zinc acetate (25 mg 3 times a day). Follow up after 11 months showed clinical and laboratory data improvement (PT 80%; PTT 34 sec (23-38), INR 1.16, ATIII 94.4% (80-120). Genetic analysis for mutation in ATP7B was planned. Most experience on Wilson disease's therapy in symptomatic patients stems from the use of chelating drugs. In contrast, a theory that is gaining ground holds that the pathogenesis of Wilson disease is related to free copper in plasma, rather than the accumulation of the element in body tissues. Therefore, the objective of treatment is to normalize the concentration of free copper in blood. Zinc, inducing the production of metallothionein that selectively binds to copper in the cells of intestinal mucosa, prevents copper absorption. The therapy traditionally used is based on zinc sulphate; zinc acetate has fewer gastrointestinal side effects. In our patient the choice of the therapy with zinc acetate as initial treatment has thus far achieved good results. The same response has been reported for a case of decompensated cirrhosis which improved after zinc sulphate monotherapy [2].",monotherapy;Wilson disease;hemolytic anemia;adolescent;therapy;patient;blood;international normalized ratio;infection;autoimmunity;ultrasound;liver weight;diagnosis;scoring system;liver biopsy;follow up;laboratory;genetic analysis;mutation;pathogenesis;plasma;tissue;intestine mucosa;absorption;gastrointestinal symptom;decompensated liver cirrhosis;female;hospital;jaundice;thrombocytopenia;Coombs test;erythrocyte;transfusion;girl;hepatomegaly;splenomegaly;thrombotic thrombocytopenic purpura;screening;liver disease;zinc acetate;copper;zinc sulfate;ceruloplasmin;zinc;metallothionein;bilirubin;blood clotting factor;antithrombin;albumin,"Marazzi, M. G.;Giardino, S.;Dufour, C.;Serafino, M.;Sperli, D.;Giacchino, R.",2009,,http://dx.doi.org/10.1016/S1590-8658%2809%2960483-7,0,0,
1916,Zinc vs. d-penicillamine treatment in children with Wilson disease and liver presentation,"Background: Zinc-based drugs seem to be as effective as d-penicillamine in the neurological presentation of Wilson disease but there are very limited data on its efficacy in patients with hepatic symptoms. The aim of the study was to compare the effects of treatment with zinc vs. d-penicillamine in a retrospective analysis of pediatric patients with Wilson disease and liver presentation. Material and Methods: We analyzed 27 children with Wilson disease before and after one year of treatment (14 pts. aged 11.7+/-3.3 y receiving zinc and 13 pts. aged 13.4+/-3.2y on d-penicillamine) in whom the therapy was not changed during the observation period. Wilson disease was diagnosed according to the Ferenci et al. scoring system and mutation analysis examination. Patients with acute and fulminant liver failure were excluded from this study. Results: Before the treatment ALT levels were slightly lower in zinc patients than in penicillamine patients (114+/-105 IU/L vs. 197+/-120 IU/L, mean +/-SD). We did not find any difference at baseline in AST, INR and GGTP between the groups. After one year of treatment there was no difference in ALT levels between the zinc and penicillamine group (respectively 56+/-22 IU/L and 50+/-18 IU/L) however the fall in ALT level was significant (p<0.05) in the penicillamine patients but not in the zinc patients. AST activity decreased significantly in both groups. Conclusions: Penicillamine induces a larger fall in ALT level than zinc therapy and might therefore be more effective in children with Wilson disease and liver presentation.",Wilson disease;liver;child;patient;aged;therapy;scoring system;mutation;examination;liver failure;international normalized ratio;zinc;penicillamine,"Janczyk, W.;Dadalski, M.;Schmidt, H.;Houwen, R.;Socha, P.",2009,June,,0,1,
1917,Diagnostic and management issues in myeloneuropathy associated with copper deficiency,"Background: Copper deficiency is a rare but under-recognised cause of myelopolyneuropathy. We present a case, coexisting with B<inf>12</inf> deficiency and discuss challenges in diagnosis and management Case Report: A 59-year-old man presented with a 14 month history of progressive sensory ataxia and spastic paraparesis. Initial blood tests showed low B<inf>12</inf>/folate. Ataxia progressed despite monthly intramuscular replacement therapy. Further investigations confirmed hypocupraemia and low caeruloplasmin with normal serum zinc. MRI brain showed only minor ischaemia. MRI spine was normal. Neurophysiology showed an axonal sensori-motor polyneuropathy. The imaging, normalnon-invasive liverstudies, normal24hoururinary copper and absence of Kayser-Fleischer rings excluded Wilson's disease. Treatment with oral copper picolinate lead to no significant clinical change. The cause of copper deficiency remains unexplained. Discussion: The largest series (13 patients) on this topic describes typical clinical features and in these cases replacement with copper halted clinical deterioration. It is important to exclude Wilson's disease, which can manifest similar serum copper measurements. Supplementation should be given with a preparation which does not contain zinc, as zinc hinders copper absorption. Copper deficiency should be considered in patients presenting with myeloneuropathy, even in the presence of low B<inf>12</inf>. Early diagnosis and treatment may prevent neurological deterioration.",copper deficiency;diagnosis;autumn;deterioration;Wilson disease;patient;nuclear magnetic resonance imaging;copper blood level;supplementation;absorption;early diagnosis;case report;human;spastic paraplegia;blood;zinc blood level;brain;ischemia;spine;neurophysiology;polyneuropathy;imaging;clinical feature;substitution therapy;copper;zinc;cyanocobalamin;ceruloplasmin;picolinic acid,"Chowdhury, F. A.;Sherwood, R.;Moran, N.;Dhawan, A.;Samuel, M.",2009,April,http://dx.doi.org/10.1136/jnnp.2008.167387,0,0,
1918,Obesity and Wilson disease in childhood and adolescence,"Background and Aim: Obesity during childhood and adolescence is commonly leading to elevated tranferases and liver steatosis, and is thought to be associated with elevated acute phase proteins. However, steatosis is also found in a variety of metabolic diseases during childhood including Wilson disease. An algorithm for a detailed differential diagnosis would be valuable. Methods: A retrospective analysis of the data of 291 obese (body mass index higher than 97% percentile) children and adolescents attending the liver or obesity outpatient clinics during the last 6 years (2003-2008) has been carried out. Standard anthropometric and laboratory parameters, virology, haptoglobin, alpha-1-antitrypsin and serum caeruloplasmin were analysed. Penicillamine challenge tests were performed in 22 patients, and 14 liver biopsies in patients with elevated transferases despite a trial of weight reduction (with exception of emergency cases). Genetic analysis and slit lamp examination was performed. Results: 41 (14.08 %) patients had elevated transferases. Average caeruloplasmin (normal range 0.220-0.605 g/L) value was 0.263 g/L (0.139 - 0.388 g/L); 9/41 (22%) subjects had values below the reference range. 22 patients had a penicillamine challenge test, with mean values of 19mug, 698 mug, 802mug and 819mug on days 1-4. 13 children had values in the intermediate range from 800-1590mg, 2 tests had values above 1590mg. Liver histology showed steatosis in 8, steatohepatitis in 1, fibrous changes in 4 and cirrhosis in 2 patients, respectively. We discovered 2 cases of Wilson disease in this group by following a multistep approach. Additionally 3 further asymptomatic homozygous relatives with Wilson disease and 4 heterozygous carriers were discovered. Realizing the problems in diagnosing Wilson disease we present an algorithm to systematically search for the disease in obese children with elevated liver enzymes. In contrast to current paediatric literature we cannot confirm the observation of elevated acute phase proteins (C-reactive protein, caeruloplasmin and alpha-1-antitrypsin) in obese children and adolescents. Conclusions: Currently, there are insufficient data to predict the incidence of Wilson disease in obese children with liver disease. Our data suggest a higher incidence than being estimated at present. All children or adolescents with liver disease should be intensively investigated towardsWilson disease. Early diagnosis should be aimed to provide early therapy prior to development of irreversible organic damage.",Wilson disease;society;obesity;childhood;adolescence;gastroenterology;nutrition;child;patient;adolescent;steatosis;algorithm;provocation test;liver disease;liver cirrhosis;hypertransaminasemia;serum;body mass;differential diagnosis;metabolic disorder;early diagnosis;therapy;fatty liver;liver biopsy;weight reduction;emergency patient;genetic analysis;slit lamp;liver histology;liver;outpatient department;laboratory;virology;heterozygote;ceruloplasmin;penicillamine;alpha 1 antitrypsin;transferase;acute phase protein;haptoglobin;protein,"Spindelbock, W.;Spindelboeck, W.;Deutschmann, A.;Lackner, K.;Weitzer, C.;Erwa, W.;Hauer, A.;Ferenci, P.;Deutsch, J.",2009,May,http://dx.doi.org/10.1097/MPG.0b013e3181aa06ea,0,0,
1919,Evaluation of the efficacy of D-penicillamine therapy in children with Wilson disease,"Aim: To evaluate the efficacy of prolonged D-penicillamine therapy in children with Wilson's disease. Methods:We examined 53 children withWilson's disease aged from 6 to 17 years old (mean age was 12 years old). Boys 25 (47%), girls 28 (53%). Hepatic formof the disease was diagnosed in 41 (77%) children, mixed form, in 12 (27%) children. All children received D-penicillamine therapy, mean dose was 17.87 mg/kg/day. We evaluated changes of liver size, serum transaminases level (ALT, AST) and urinary excretion of copper during prolonged course of therapy with D-penicillamine (cuprenil). Results: Before the start of treatment in 21 (39.6%) children liver size was increased (0.5-2 cm from costal arch), include 3 (14%) children with mixed form of Wilson's disease. During treatment liver size was reduced in all children, in 15 (28%) children liver size became normal. Mean serumALT level before the start of therapy was 112.8 UI/L (normal 5-40), in 6 months of therapy 44 UI/L, during the next 5 years it varied from minimum (23.7 UI/L) to maximum (76.6 UI/L), mean level was 44.8 UI/L. Mean serum AST level before start of therapy was 79.74 UI/L (normal 5-42), in 6 months 42.14 UI/L, in 5 years 31 UI/L. Urinary excretion of copper before start of therapy was 286mug/day (normal to 50mug/day), in D-penicillamine loading test 1961mg/day (normal 600- 800). In 6 months of therapy this level was 971.5mug/day, in 1 year 965mug/day, in 2 years 685.4mg/day, in 5 years 524mug/day. Thus, in a year mean level of urinary excretion of copper decreased to high limit of the norm, and after that, during 5-year period of observation was not higher than 700mug/day. Conclusions: In all children during D-penicillamine (cuprenil) therapy positive changes were registered: liver size was reduced; serum transaminases level and urinary excretion of copper were decreased.",child;therapy;society;Wilson disease;nutrition;gastroenterology;liver size;urinary excretion;aminotransferase blood level;girl;serum;loading test;boy;penicillamine;copper,"Zubovich, A.;Strokova, T.;Kaganov, B.;Pavlovskaya, E.",2009,May,http://dx.doi.org/10.1097/MPG.0b013e3181aa06ea,0,0,
1920,EuroWilson: The first prospective study of Wilson's disease in Europe,"Aims and Methods: To establish a European database of Wilson disease and assess feasibility of paediatric clinical trials. Patients diagnosed between January 1, 2005 and November 30, 2008 were entered using a Web-based secure protocol. A previously validated score was used to verify diagnoses. Results: 353 cases (176 female), aged 0.25-56.1 (mean 20.4, median 17.6) years from 321 families were entered. Apparent incidence (as cases/million population/35 months) was higher in central Europe (eg, Poland 2.78, Austria 2.53) than western (eg, France 0.56, UK 0.48, Spain 0.32). Patients homozygous for the common mutation H1069Q were older (27.8+/-12.2 years, n = 65) than the others (19.3+/-12.5 years). Patients aged <18 years (N = 181, female = 88) had a more homogeneous geographic spread. Country by country variations in the percentage of paediatric cases probably demonstrates variable adult case ascertainment, eg, Poland 18%, UK 86%. 2 non-EU countries,Turkey and India, contributed 27 and 16 paediatric cases, respectively. The mean (median) BMI SDS in 81 cases whose height was measured was 1.8 (2.06). The median diagnostic score was 6 (range 4-10); KFrings were present in 50; caeruloplasmin was measured in 172, and was >0.18 g/L in 34; urine copper was measured in 161, and a penicillamine challenge was done in 66; 105 had a liver biopsy, but only 78 had a liver copper assay, of whom 11 had a result <250mug/g; 2 mutations were identified in 82, of whom26 were homozygotes (9 for H1069Q). Severity of liver disease varied: 5% had hepatic encephalopathy, 32% had severe and 18% mild liver disease, 38% abnormal LFTs only, and only 7% had no hepatic abnormalities. Neurological abnormalities were present in 21%, and were severe in 5%, with no correlation with severity of liver disease. There was a wide variety of initial treatments and doses. Conclusions: This first prospective study of WD demonstrates: (1) the higher incidence in eastern Europe; (2) diagnosis remains difficult because lack of sensitivity in each diagnostic parameter and selective use of tests but is aided by a scoring system; (3) relatively high BMI SDS at diagnosis; (4) wide phenotypic and genotypic variation; (5) in patients <18 years liver failure is rare, but 93% cases show some hepatic abnormality, and 21% have some neurological abnormality; (6) inclusion of cases from non-EU countries will be necessary to mount paediatric RCTs.",gastroenterology;society;Europe;nutrition;prospective study;Wilson disease;diagnosis;patient;liver disease;female;Poland;mutation;United Kingdom;Spain;adult;India;height;urine;liver biopsy;liver;assay;homozygote;hepatic encephalopathy;Eastern Europe;scoring system;genetic variability;liver failure;data base;clinical trial;Austria;France;copper;penicillamine;ceruloplasmin,"Tanner, S.;Dhawan, A.;Socha, P.;Loudianos, G.;Lszl, S.;Parker, S.;Vegnente, A.;Houwen, R.;Sarles, J.;Deutsch, J.",2009,May,http://dx.doi.org/10.1097/MPG.0b013e3181aa06ea,0,0,
1921,Successful treatment of fulminant wilson's disease by plasma exchange,"Background: Treatment of Fulminant Wilson's diseases still carries a high mortality without liver transplant. There is no acceptable treatment other than liver transplant. Few case reports have successfully treated fulminant Wilsons, disease with plasma exchange. Case Report: We report here a case of a 14 years old boy who presented to our hospital with fulminant Wilson's disease, including low AST and AlT and Alkaline phosphatase, high bilirubin 38 mg/dl, INR 3.1, creatinine 0.6 mg/dl, grade II hepatic encephalopathy, mild ascites, positive Kayser Fleischer ring, low ceruloplasmin, high serum copper, and a hematological picture consistent with hemolysis. He was treated with 5 sessions of plasma exchange with improvised synthetic function, in addition to conservative treatment, and by the end of last plasma exchange session he was taken off the liver transplant list and was started on Wilson's disease treatment. He improved markedly over the last year and became asymptomatic with an almost normal synthetic function He is now only D-Penicillamine and Zinc. Colclusion: Successful treatment of WD by plasma exchange and other supportive measure has been described. This case another example. This could be due to removing excess cupper as the crucial offending agent rather than removing other agents since this treatment is not successful in other etiologies of FHF.",Wilson disease;plasmapheresis;society;liver transplantation;liver graft;case report;etiology;mortality;boy;hospital;international normalized ratio;hepatic encephalopathy;ascites;copper blood level;hemolysis;conservative treatment;penicillamine;zinc;alkaline phosphatase;bilirubin;ceruloplasmin;creatinine,"Jarrad, A.;Hammoudi, S.;Saed, R.;Obed, A.;Al Bashir, A.",2009,July,,0,0,
1922,"Wilson disease in children; A six-year experience, 2001-2008","Aims: To describe the clinical and laboratory features of children with Wilson Disease presenting to the Hospital for Sick Children, a large tertiary care pediatric centre. Methods: Patients diagnosed with Wilson Disease between 2001 and 2008 were identified from clinical databases and a retrospective chart review was performed. Results: Eleven patients were identified, with an average age at presentation of 12 years (range 7-17 years). Nine of 11 patients had a hepatic presentation including jaundice, hepatomegaly, ascites, pale stools, or hematemesis. Of these patients, three had overlapping neuropsychiatric symptoms ranging from encephalopathy to paresthesias. Five of the nine patients who presented with liver decompensation also exhibited Coomb's negative haemolytic anemia. Eighteen percent (2/11) presented with isolated neurological complaints (developmental delay and ataxia in one, parasthesiae in the other). These children presented at a younger age (average 7 y) in comparison to the group mean of 12 y. Five of 11 children (45%) presented with Kaiser Fleischer rings. Only one case had a positive family history of Wilson Disease; this family had a history of consanguinity. Through family screening, two separate children were identified to be asymptomatic carriers. At presentation, the average (range) laboratory values were as follows: ceruloplasmin 115 mg/L (27 - 253 mg/l), 24 hour urinary copper excretion 13.7 umol (0.290-60.5), INR 1.9 (0.9-4.3), total bilirubin 85 (4-361), albumin 29 (23-48), AST 238 (44-1083), alkaline phosphatase 251 (20-824), WBC 10.7 (3.7-25.2), haemoglobin 101 g/l (54-134) and platelets 205 (88-460). The new Wilson Disease severity index was calculated for each patient, and ranged from 3 to 16 (on a possible scale of 0 to 20). Among the three patients who scored 11 or above and were therefore predicted to require liver transplantation, one recovered with medical therapy. Children were treated with a combination of chelation agents including penicillamine, trientine and/or zinc. Clinical outcomes were assessed at a mean of 2.5 years (range 0.14-5.8) following diagnosis. None of the children died. Three patients underwent liver transplantation (two soon after diagnosis and one patient five years thereafter). One recently diagnosed patient is currently awaiting transplant. Two patients developed neuropsychiatric symptoms despite chelation treatment. Conclusions: Children with Wilson Disease demonstrate a variety of clinical presentations, have a high likelihood of response to chelation therapy, and occasionally require liver transplantation. The new Wilson Disease index should be used with caution because it does not reliably indicate the need for transplantation.",child;Wilson disease;gastrointestinal disease;patient;liver transplantation;laboratory;diagnosis;transplantation;consanguinity;thrombocyte;disease severity;therapy;chelation;chelation therapy;hospital;tertiary health care;data base;medical record review;jaundice;ascites;feces;hematemesis;brain disease;paresthesia;international normalized ratio;anemia;neurologic disease;family history;hepatomegaly;screening;excretion;decompensated liver cirrhosis;bilirubin;albumin;alkaline phosphatase;hemoglobin;chelating agent;penicillamine;trientine;zinc;ceruloplasmin;copper,"Avinashi, V.;Ling, S.",2009,,,0,1,
1923,Prospective look at the use of trientene in Wilsons disease: A safer alternative,"We report the progress of 5 patients diagnosed with Wilson' Disease with age range between 13 and 30 years, 3 females and 2 males who developed multiple side effects with initiation of penicillamine therapy including thrombocytopenia (3 patients), allergic skin reactions (3 patients), worsening of neuropsychiatric features (1 patient) and status dystonicus (1 patient). These side effects developed within a month to 6 months after initiation of penicillamine. The stopping of penicillamine therapy and initiation of therapy with Trientene brought about improvement of neuropsychiatric features and amelioration of features of status dystonicus as well as resolution of thrombocytopenia. We would like to propose that patients with Wilsons disease once initiated with penicillamine therapy be followed up closely to look for these side effects and suggest that possibly trientene would be a safer alternative to penicillamine therapy in a subgroup of Wilson's disease patients and possibly better served even as initial therapy.",neurology;patient;therapy;side effect;Wilson disease;thrombocytopenia;male;skin allergy;female;penicillamine,"Viswanathan, S.;Puvanarajah, S. D.;Rafia, M. H.",2009,October,,0,1,
1924,"Clinical presentation, diagnosis and long-term outcome of 35 patients with Wilson's disease","Purpose: Wilson disease is an inherited, autosomal recessive disorder. Subsequent copper accumulation in the liver, brain and other tissues produces hepatic, neurological, psychiatric, ophthalmological, and other derangements clinical manifestations. We describe the clinical characteristics, treatment and follow-up of a cohort of 35 patients with Wilson's disease. Methods: We reviewed the medical records and cerebral imaging of 35 patients with Wilson's disease, followed in the National Institute of Neurology in Tunis. Diagnosis of the disease was based on the presence of abnormal biochemical tests: raised urinary copper excretion, decreased serum ceruloplasmin and serum copper levels. Results: The median age of onset was 18.9 years (range 4 to 56 years). The observation time was up to 7.5 years. The most common presenting symptoms were tremor (42.8%), dysarthria (22.8%) and behavioural disturbances (17.1%). A Kayser-Fleischer ring was observed in 45.7%. The cerebral imaging was abnormal in 62.5% of the patients. Atrophy of the cerebrum with signal abnormalities in the cerebral gray matter were observed in 25%. One patient had severe subcortical white matter abnormalities which are unusual features in Wilson's disease. Patient's clinical symptoms remained stable with D-penicillamine or improved during the observation period in 65.7% of the cases, while 6 patients out of 35 got worse. Conclusion: Diagnosis of Wilson's disease may be difficult in the absence of typical symptoms and in asymptomatic siblings. D-penicillamine is a safe and effective long term treatment in patients with Wilson's disease. If treatment is begun early enough, a normal quality of life can be expected.",patient;Wilson disease;diagnosis;neurology;brain;imaging;dysarthria;atrophy;gray matter;white matter;sibling;liver;long term care;tissue;medical record;autosomal recessive disorder;quality of life;excretion;ceruloplasmin blood level;copper blood level;onset age;tremor;follow up;copper;penicillamine,"Ellini, S.;Ammar, N.;Larnaout, A.;Hentati, F.;Zouari, M.",2009,October,,0,0,
1925,Essential tremor? Wilson disease?,"Wilson disease is an autosomal recessive disorder of copper metabolism that is associated with degenerative changes in basal ganglia. The gene for Wilson disease is located on the long arm of chromosome 13 and encodes a copper-transporting P-type ATPase that is expressed in liver and kidney. Clinical symptoms are complex with neurologic symptoms such as tremor, dysarthria, psychiatric disorders etc, predominant hepatic disease or mixed forms. 40-50% of the patients represent with the neurologic abnormalities and resting or postural tremor is the first clinical sign in half of them. Case report: He had tremor in his hands for ten years and he had used mysoline and propranolol for tremor which were not effective. He had a family history of essential tremor in his father and uncle. His physical examination was normal except postural tremor. His mental status and school performance was normal. Even though there was no family history ofWilson disease, plasma ceruloplasmine level was low (16 mg/dl), urine copper in 24-hour urine collection was high (62 microgram). Cranial magnetic resonance revealed hyperintense lesions bilateral at globus pallidus and putamen in T2 weighted images. He had a diagnosis of Wilson disease and started the therapy with penicillamine, zinc, vitamin B and a diet low in copper. Conclusion: Wilson disease always must be in mind in all movement disorders of childhood even though there is long term quiet neurologic signs and no hepatic involvement.",Wilson disease;essential tremor;society;tremor;family history;urine;neurologic disease;mental health;academic achievement;plasma;nuclear magnetic resonance;globus pallidus;putamen;diagnosis;diet;motor dysfunction;childhood;therapy;autosomal recessive disorder;copper metabolism;basal ganglion;gene;arm;chromosome 13;kidney;dysarthria;liver disease;patient;case report;liver;father;physical examination;mental disease;copper;ceruloplasmin;penicillamine;zinc;vitamin B group;copper exporting adenosine triphosphatase;primidone;propranolol,"Gokben, S.;Arikan, C.;Serdaroglu, G.;Yilmaz, S.;Tekgul, H.;Aydogdu, S.",2009,September,http://dx.doi.org/10.1016/S1090-3798%2809%2970357-5,0,0,
1926,"Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia - A new metabolic disorder","We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year-old girl born to consanguineous parents. Blood manganese levels were >3000 nmol/L (normal range <320 nmol/ L) and MRI revealed signal abnormalities of the basal ganglia consistent with manganese deposition. An older brother with the same phenotype died at 18 years, suggesting a potentially lethal, autosomal recessive disease. This disorder is probably caused by a defect of manganese metabolism with the accumulation of manganese in the liver and the basal ganglia similar to the copper accumulation in Wilson disease. In order to assess the genetic basis of this syndrome we investigated two candidate genes: ATP2C2 and ATP2A3 encoding the manganese-transporting calcium-ATPases, SPCA2 and SERCA3, respectively. Genotyping of the patient and the family for microsatellite markers surrounding ATP2C2 and ATP2A3 excluded these genes. The patient was found to be heterozygous for both gene loci. Despite the unknown pathophysiology, we were able to develop a successful treatment regime. Chelation therapy with disodium calcium edetate combined with iron supplementation is the treatment of choice, lowering blood manganese levels significantly and improving clinical symptoms. © Springer Science+Business Media B.V. 2008.",adolescent;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/th [Therapy];basal ganglion;blood analysis;case report;chelation therapy;clinical feature;conference paper;consanguineous marriage;drug dose reduction;dystonia/di [Diagnosis];echography;family history;female;gene locus;genotype;hepatomegaly/di [Diagnosis];heterozygosity;human;human tissue;hypermagnesemia/di [Diagnosis];hypermagnesemia/dt [Drug Therapy];iron therapy;jaundice;liver biopsy;liver cirrhosis/di [Diagnosis];low drug dose;metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/th [Therapy];microsatellite marker;motor dysfunction;neurologic disease/dt [Drug Therapy];polycythemia/di [Diagnosis];portal hypertension/di [Diagnosis];school child;splenomegaly/di [Diagnosis];unspecified side effect/si [Side Effect];vitamin supplementation;walking difficulty;adenosine triphosphatase (calcium)/ec [Endogenous Compound];adenosine triphosphate/ec [Endogenous Compound];adenosine triphosphate 2A3/ec [Endogenous Compound];adenosine triphosphate 2C2/ec [Endogenous Compound];alpha tocopherol;carbidopa plus levodopa/dt [Drug Therapy];edetate calcium disodium/ae [Adverse Drug Reaction];edetate calcium disodium/dt [Drug Therapy];ferrous fumarate/do [Drug Dose];ferrous fumarate/dt [Drug Therapy];ferrous ion/dt [Drug Therapy];ferrous ion/po [Oral Drug Administration];manganese/ec [Endogenous Compound];multivitamin;penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];sarcoplasmic reticulum calcium transporting adenosine triphosphatase/ec [Endogenous Compound];sarcoplasmic reticulum calcium transporting adenosine triphosphatase 3/ec [Endogenous Compound];secretory pathway calcium transporting adenosine triphosphatase/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Tuschl, K.;Mills, P. B.;Parsons, H.;Malone, M.;Fowler, D.;Bitner-Glindzicz, M.;Clayton, P. T.",2008,April,http://dx.doi.org/10.1007/s10545-008-0813-1,0,0,
1927,Tetrathiomolybdate protects against bile duct ligation-induced cholestatic liver injury and fibrosis,"Tetrathiomolybdate (TM), a potent copper-chelating drug, was initially developed for the treatment of Wilson's disease. Our working hypothesis is that the fibrotic pathway is copper-dependent. Because biliary excretion is the major pathway for copper elimination, a bile duct ligation (BDL) mouse model was used to test the potential protective effects of TM. TM was given in a daily dose of 0.9 mg/mouse by means of intragastric gavage 5 days before BDL. All the animals were killed 5 days after surgery. Plasma liver enzymes and total bilirubin were markedly decreased in TM-treated BDL mice. TM also inhibited the increase in plasma levels of tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 seen in BDL mice. Cholestatic liver injury was markedly attenuated by TM treatment as shown by histology. Hepatic collagen deposition was significantly decreased, and it was paralleled by a significant suppression of hepatic smooth muscle alpha-actin and fibrogenic gene expression in TM-treated BDL mice. Although the endogenous antioxidant ability was enhanced, oxidative stress as shown by malondialdehyde and 4-hydroxyalkenals, hepatic glutathione/oxidized glutathione ratio, was not attenuated by TM treatment, suggesting the protective mechanism of TM may be independent of oxidative stress. In summary, TM attenuated BDL-induced cholestatic liver injury and fibrosis in mice, in part by inhibiting TNF-alpha and TGF-beta1 secretion. The protective mechanism seems to be independent of oxidative stress. Our data provide further evidence that TM might be a potential therapy for hepatic fibrosis.",animal experiment;animal model;animal tissue;article;bile duct ligation;biliary excretion;controlled study;drug effect;drug inhibition;drug mechanism;gene expression;histopathology;liver fibrosis;liver injury;male;mouse;nonhuman;oxidative stress;priority journal;4 hydroxyalkenal derivative;alkene derivative;alpha smooth muscle actin;bilirubin/ec [Endogenous Compound];copper;glutathione;liver enzyme/ec [Endogenous Compound];malonaldehyde;tetrathiomolybdic acid/ig [Intragastric Drug Administration];tetrathiomolybdic acid/pd [Pharmacology];transforming growth factor beta1;tumor necrosis factor alpha;unclassified drug,"Song, M.;Song, Z.;Barve, S.;Zhang, J.;Chen, T.;Liu, M.;Arteel, G. E.;Brewer, G. J.;McClain, C. J.",2008,May,http://dx.doi.org/10.1124/jpet.107.131227,0,0,
1928,"Wilson protein expression, copper excretion and sweat production in sweat glands of Wilson disease patients and controls","Background: In Wilson disease, copper is not sufficiently excreted into bile due to the absence or malfunction of the Wilson protein copper ATPase in the excretory pathway of hepatocytes. Copper is found in sweat. It is unknown if the Wilson protein plays a role in copper excretion into sweat. It is the aim of this study to investigate Wilson protein expression in sweat glands and analysing its effects on copper excretion into sweat in controls and patients with Wilson disease. Methods: Immunofluorescent analysis of the Wilson protein in skin samples from normal rat, LEC rat and human skin biopsies were performed. Pilocarpin-induced sweat gland stimulation by iontophoretic transfer adapted from the methods used for cystic fibrosis sweat test was used for sweat induction. Sweat volume, sweat copper concentration, serum ceruloplasmin and serum copper were analysed in 28 Wilson patients and 21 controls. Results: The Wilson protein is expressed in human and rat sweat gland epithelia. Copper concentration in sweat is not significantly different between controls and Wilson patients. Wilson patients produce significantly smaller volumes of sweat compared to controls. Sweat production is partially reversible in Wilson patients under medical treatment for Wilson disease or after liver transplantation. Conclusion: Wilson patients show a reduced sweat production with unaltered sweat copper concentration. The Wilson protein might play an important role in physiological sweat production. © 2008 Schaefer et al; licensee BioMed Central Ltd.",adult;animal tissue;article;bile flow;clinical article;concentration (parameters);controlled study;female;human;human tissue;immunofluorescence;iontophoresis;liver cell;liver transplantation;male;nonhuman;protein expression;rat;skin biopsy;sweat gland;sweat test;sweating;treatment outcome;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pilocarpine;trientine/cb [Drug Combination];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Schaefer, M.;Schellenberg, M.;Merle, U.;Weiss, K. H.;Stremmel, W.",2008,17 Jul,http://dx.doi.org/10.1186/1471-230X-8-29,0,0,
1929,Diagnosis and treatment of Wilson disease: An update,,anemia/si [Side Effect];aplastic anemia/si [Side Effect];bone marrow depression/si [Side Effect];clinical feature;combination chemotherapy;computer assisted tomography;disease association;drug absorption;drug dose reduction;drug half life;drug tolerability;elastosis/si [Side Effect];fatty liver/di [Diagnosis];fever/si [Side Effect];food intake;gastritis/si [Side Effect];genetic analysis;hemosiderosis/si [Side Effect];human;hypersensitivity reaction/si [Side Effect];leukopenia/si [Side Effect];liver biopsy;liver cirrhosis/dt [Drug Therapy];liver disease;liver failure/dt [Drug Therapy];liver function test;liver toxicity/si [Side Effect];liver transplantation;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];nephrotic syndrome/si [Side Effect];neuroimaging;neurologic disease/si [Side Effect];neutropenia/si [Side Effect];newborn screening;nuclear magnetic resonance imaging;pancreatitis/si [Side Effect];patient care;pregnancy;priority journal;proteinuria/si [Side Effect];rash/si [Side Effect];retinitis/si [Side Effect];review;sideroblastic anemia/si [Side Effect];skin disease/si [Side Effect];splenomegaly;thrombocytopenia/si [Side Effect];treatment failure;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];alpha tocopherol/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];dimercaprol/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/cm [Drug Comparison];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];pyridoxine/dt [Drug Therapy];pyridoxine/po [Oral Drug Administration];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];trientine/pd [Pharmacology];uric acid/ec [Endogenous Compound];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/cb [Drug Combination];zinc derivative/cm [Drug Comparison];zinc derivative/dt [Drug Therapy];zinc derivative/pd [Pharmacology],"Roberts, E. A.;Schilsky, M. L.",2008,June,http://dx.doi.org/10.1002/hep.22261,0,0,
1930,Estimation of free copper ion concentrations in blood serum using T<inf>1</inf> relaxation rates,"The water proton relaxation rate constant R<inf>1</inf> = 1/T<inf>1</inf> (at 60 MHz) of blood serum is substantially increased by the presence of free Cu<sup>2+</sup> ions at concentrations above normal physiological levels. Addition of chelating agents to serum containing paramagnetic Cu<sup>2+</sup> nulls this effect. This was demonstrated by looking at the effect of adding a chelating agent-D-penicillamine (D-PEN) to CuSO<inf>4</inf> and CuCl<inf>2</inf> aqueous solutions as well as to rabbit blood serum. We propose that the measurement of water proton spin-lattice relaxation rate constants before and after chelation may be used as an alternative approach for monitoring the presence of free copper ions in blood serum. This method may be used in the diagnosis of some diseases (leukaemia, liver diseases and particularly Wilson's disease) because, in contrast to conventional methods like spectrophotometry which records the total number of both bound and free ions, the proton relaxation technique is sensitive solely to free paramagnetic ions dissolved in blood serum. The change in R<inf>1</inf> upon chelation was found to be less than 0.06 s<sup>-1</sup> for serum from healthy subjects but greater than 0.06 s<sup>-1</sup> for serum from untreated Wilson's patients. © 2008.",Chelation;d-pen;Serum;T<inf>1</inf> water proton relaxation;algorithm;article;blood;blood analysis;chemistry;evaluation;human;methodology;nuclear magnetic resonance spectroscopy;reproducibility;sensitivity and specificity;Wilson disease/di [Diagnosis];chelating agent;copper;ion,"Blicharska, B.;Witek, M.;Fornal, M.;MacKay, A. L.",2008,September,http://dx.doi.org/10.1016/j.jmr.2008.05.018,0,0,
1931,Anesthesia for a patient with Wilson's disease - A case report,,anesthesia;article;blood;case report;female;human;injury;metabolism;middle aged;nerve block;pathophysiology;rotator cuff/su [Surgery];Wilson disease/th [Therapy];amide;chelating agent/dt [Drug Therapy];copper;local anesthetic agent;penicillamine/dt [Drug Therapy];ropivacaine,"Hobaika, A. B. D. S.",2008,February,,0,0,
1932,Effect of D-penicillamine on liver fibrosis and inflammation in Wilson disease,"BACKGROUND: Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients. MATERIALS AND METHODS: Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist. RESULTS: Of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P < .05). CONCLUSION: D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.",adolescent;adult;article;child;comparative study;disease course;drug effect;female;hepatitis/et [Etiology];hepatitis/pc [Prevention];hospitalization;human;infant;liver;liver cirrhosis/et [Etiology];liver cirrhosis/pc [Prevention];liver transplantation;male;metabolism;pathology;preschool child;retrospective study;treatment outcome;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];chelating agent/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Kazemi, K.;Geramizadeh, B.;Nikeghbalian, S.;Salahi, H.;Bahador, A.;Reza Nejatollahi, S. M.;Mohsen Dehghani, S.;Dehghani, M.;Kakaei, F.;Malek-Hosseini, S. A.",2008,Dec,,0,1,
1933,Liver disease in pregnancy,"Abnormal liver tests occur in 3%-5% of pregnancies, with many potential causes, including coincidental liver disease (most commonly viral hepatitis or gallstones) and underlying chronic liver disease. However, most liver dysfunction in pregnancy is pregnancy-related and caused by 1 of the 5 liver diseases unique to the pregnant state: these fall into 2 main categories depending on their association with or without preeclampsia. The preeclampsia-associated liver diseases are preeclampsia itself, the hemolysis (H), elevated liver tests (EL), and low platelet count (LP) (HELLP) syndrome, and acute fatty liver of pregnancy. Hyperemesis gravidarum and intrahepatic cholestasis of pregnancy have no relationship to preeclampsia. Although still enigmatic, there have been recent interesting advances in understanding of these unique pregnancy-related liver diseases. Hyperemesis gravidarum is intractable, dehydrating vomiting in the first trimester of pregnancy; 50% of patients with this condition have liver dysfunction. Intrahepatic cholestasis of pregnancy is pruritus and elevated bile acids in the second half of pregnancy, accompanied by high levels of aminotransferases and mild jaundice. Maternal management is symptomatic with ursodeoxycholic acid; for the fetus, however, this is a high-risk pregnancy requiring close fetal monitoring and early delivery. Severe preeclampsia itself is the commonest cause of hepatic tenderness and liver dysfunction in pregnancy, and 2%-12% of cases are further complicated by hemolysis (H), elevated liver tests (EL), and low platelet count (LP) - the HELLP syndrome. Immediate delivery is the only definitive therapy, but many maternal complications can occur, including abruptio placentae, renal failure, subcapsular hematomas, and hepatic rupture. Acute fatty liver of pregnancy is a sudden catastrophic illness occurring almost exclusively in the third trimester; microvesicular fatty infiltration of hepatocytes causes acute liver failure with coagulopathy and encephalopathy. Early diagnosis and immediate delivery are essential for maternal and fetal survival. Copyright © 2007 by the American Association for the Study of Liver Diseases.",adrenal insufficiency/si [Side Effect];biliary tract disease;bradycardia/dt [Drug Therapy];chronic liver disease/dt [Drug Therapy];cleft palate/si [Side Effect];clinical feature;clinical trial;cytomegalovirus infection;delta agent hepatitis;embryopathy/dt [Drug Therapy];endoscopic retrograde cholangiopancreatography;endoscopic sphincterotomy;fatty liver/di [Diagnosis];fatty liver/et [Etiology];fetus disease/si [Side Effect];gallstone;HELLP syndrome/di [Diagnosis];HELLP syndrome/dt [Drug Therapy];HELLP syndrome/et [Etiology];hepatitis A;hepatitis B;hepatitis C;hepatitis E;herpes simplex;human;hydration;hyperemesis gravidarum/th [Therapy];immunoprophylaxis;infection prevention;intrahepatic cholestasis/di [Diagnosis];intrahepatic cholestasis/dt [Drug Therapy];intrahepatic cholestasis/et [Etiology];intrauterine growth retardation/si [Side Effect];liver biopsy;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver dysfunction;morbidity;mortality;nutritional support;outcome assessment;patient counseling;preeclampsia;pregnancy;pregnancy termination;priority journal;pruritus/dt [Drug Therapy];rehydration;review;risk factor;treatment indication;unspecified side effect/si [Side Effect];vaccination;virus hepatitis;virus infection;Wilson disease/dt [Drug Therapy];adefovir/dt [Drug Therapy];azathioprine/dt [Drug Therapy];beta adrenergic receptor blocking agent/ae [Adverse Drug Reaction];beta adrenergic receptor blocking agent/dt [Drug Therapy];betamethasone/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];dexamethasone/dt [Drug Therapy];interferon;lamivudine/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester;octreotide/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/ae [Adverse Drug Reaction];prednisone/dt [Drug Therapy];rapamycin;ribavirin/ae [Adverse Drug Reaction];tacrolimus/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];ursodeoxycholic acid/ct [Clinical Trial];ursodeoxycholic acid/do [Drug Dose];ursodeoxycholic acid/dt [Drug Therapy];vasopressin,"Hay, J. E.",2008,March,http://dx.doi.org/10.1002/hep.22130,0,0,
1934,Liver ischemia and ischemia-reperfusion induces and trafficks the multi-specific metal transporter Atp7b to bile duct canaliculi: Possible preferential transport of iron into bile,"Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia-reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia-reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia-reperfusion. Thus, we conclude that liver ischemia and ischemia-reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile. © 2007 Humana Press Inc.",Atp7b;Copper;Liver ischemia;Rats;Trafficking;anesthesia;animal experiment;animal model;article;bile;bile duct;bile flow;controlled study;enzyme activity;immunohistochemistry;iron transport;laparotomy;liver;liver cell;male;mass spectrometry;nonhuman;rat;reperfusion injury;sham procedure;Western blotting;bile acid;glutathione;iron;manganese;metal;phosphatase;sodium chloride;zinc,"Goss, J. A.;Barshes, N. R.;Karpen, S. J.;Gao, F. Q.;Wyllie, S.",2008,April,http://dx.doi.org/10.1007/s12011-007-8057-8,0,0,
1935,Late onset Wilson's disease: Therapeutic implications,"The clinical symptoms of Wilson's disease (WD) usually develop between 3 and 40 years of age and include signs of liver and/or neurologic and psychiatric disease. We report on an 84-year-old woman with WD. Despite the absence of treatment, the only symptom she presented with, until the age of 74 years, was Kayser-Fleisher rings. At the age of 74, she developed slightly abnormal liver function. This case raises the following issues: (a) Should WD be considered in all patients of all ages who manifest signs related to the disease? (b) Are ATP7B mutations fully penetrant? (c) Should all patients diagnosed presymptomatically receive anticopper therapy? © 2008 Movement Disorder Society.",Genotype;Late onset;Phenotype;Treatment;Wilson's disease;adult;aged;albumin blood level;aphasia;article;case report;ceruloplasmin blood level;computer assisted tomography;copper urine level;cornea disease;depression;echography;enzymatic assay;family;family history;female;genetic counseling;hemiparesis;human;jaundice;Kayser Fleisher ring;liver disease;male;missense mutation;nuclear magnetic resonance imaging;onset age;priority journal;transient ischemic attack;tremor;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Czlonkowska, A.;Rodo, M.;Gromadzka, G.",2008,30 Apr,http://dx.doi.org/10.1002/mds.21985,0,0,
1936,Hyperprolactinaemia - Like symptoms in Wilson's disease. [Polish],"Wilson's disease is a rare genetic disorder of copper metabolism with a hepatic or neurological presentation. Wilson's disease may occur under a variety of clinical conditions. The complex clinical presentation causes that the diagnosis rests on a high index of suspicion. We present an atypical case of this disorder in a 22-year-old woman, in whom initial clinical picture (oligomenorrhea/amenorrhea symptoms and galactorrhea) suggested the presence of prolactinoma or the other forms of hyperprolactinaemia. After the diagnosis was established and zinc sulphate treatment implemented, her clinical status improved considerably. The present report suggests that Wilson's disease should be taken into account in a differential diagnosis of galactorrhea of an unknown origin and in patients with hyperprolactinaemia-like symptoms when prolactin level is within the normal limits.",Amenorrhea/ oligomenorrhea;Clinical presentation;Galactorrhea;Hyperprolactinaemia;Wilson's disease;adult;amenorrhea/et [Etiology];article;case report;differential diagnosis;female;human;hyperprolactinemia/di [Diagnosis];hyperprolactinemia/dt [Drug Therapy];hyperprolactinemia/et [Etiology];prolactinoma/di [Diagnosis];Wilson disease/co [Complication];Wilson disease/di [Diagnosis];zinc sulfate/dt [Drug Therapy],"Krysiak, R.;Okopien, B.",2008,,,0,0,
1937,Atp7b<sup>-/-</sup> mice as a model for studies of Wilson's disease,"Wilson's disease is a severe human disorder of copper homoeostasis. The disease is associated with various mutations in the ATP7B gene that encodes a copper-transporting ATPase, and a massive accumulation of copper in the liver and several other tissues. The most frequent disease manifestations include a wide spectrum of liver pathologies as well as neurological and psychiatric abnormalities. A combination of copper chelators and zinc therapy has been used to prevent disease progression; however, accurate and timely diagnosis of the disease remains challenging. Similarly, side effects of treatments are common. To understand better the biochemical and cellular basis of Wilson's disease, several animal models have been developed. This review focuses on genetically engineered Atp7b<sup>-/-</sup> mice and describes the properties of these knockout animals, insights into the disease progression generated using Atp7b<sup>-/-</sup> mice, as well as advantages and limitations of Atp7b<sup>-/-</sup> mice as an experimental model for Wilson's disease. © 2008 Biochemical Society.",atp7a;atp7b;Copper;Liver;Mouse model;Wilson's disease;clinical feature;copper blood level;diagnostic test;disease course;disease model;gene mutation;human;knockout mouse;liver disease;metal metabolism;mouse strain;nerve degeneration;nonhuman;onset age;priority journal;protein expression;protein function;review;species difference;transport kinetics;urine level;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper exporting adenosine triphosphatase/ec [Endogenous Compound];messenger RNA/ec [Endogenous Compound],"Lutsenko, S.",2008,,http://dx.doi.org/10.1042/BST0361233,0,0,
1938,Acute wilson disease associated with e beta-thalassemia,"We report on an 11-year-old girl with concomitant Ebeta thalassemia (EbetaT) and Wilson disease (WD). She was diagnosed with EbetaT at 2 years of age, but the coexistence of WD could only be established at 11 years. The diagnosis of the later was based on the clinical presentation of hepatitis and severe Coomb's negative hemolytic anemia, coupled with laboratory evidence of WD. To our knowledge, this is the first report on the cooccurrence of EbetaT and WD. As both the conditions are associated with variable degrees of hemolysis, WD in the setting of EbetaT may remain masked and consequently remain undiagnosed for a long time. Sudden, severe hemolysis in a patient of thalassemia may be explained by the coexistence of additional pathology, in this case WD. © 2008 Lippincott Williams & Wilkins.",Eb-thalassemia;Hemolysis;Wilson disease;article;beta thalassemia/di [Diagnosis];beta thalassemia/th [Therapy];case report;child;clinical feature;disease association;e beta thalassemia/di [Diagnosis];e beta thalassemia/th [Therapy];erythrocyte transfusion;female;gastrointestinal endoscopy;high performance liquid chromatography;human;liver function test;priority journal;school child;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Thapa, R.;Mukherjee, K.",2008,December,http://dx.doi.org/10.1097/MPH.0b013e31818c00fc,0,0,
1939,Rapid diagnosis of Wilson disease in acute liver failure: No more waiting for the ceruloplasmin level?,,albumin dialysis;alkaline phosphatase blood level;aspartate aminotransferase blood level;bilirubin blood level;biochemistry;ceruloplasmin blood level;copper blood level;diagnostic accuracy;early diagnosis;early intervention;editorial;hemoglobin blood level;heterozygote;human;liver failure/co [Complication];liver transplantation;patient selection;priority journal;prothrombin time;sensitivity and specificity;watchful waiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper;hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium;trientine,"O'Brien, A.;Williams, R.",2008,October,http://dx.doi.org/10.1002/hep.22587,0,0,
1940,Diagnostic approach and management of liver failure in children. [French],,Child;Liver insufficiency;Liver transplantation;article;brain edema/dt [Drug Therapy];diagnostic procedure;digestive system hemorrhage/dt [Drug Therapy];drug intoxication/dt [Drug Therapy];galactosemia/cn [Congenital Disorder];herpes simplex;human;infection;liver biopsy;liver failure/di [Diagnosis];liver failure/su [Surgery];metabolic disorder;patient care;prognosis;virus hepatitis/dt [Drug Therapy];virus hepatitis/et [Etiology];virus hepatitis/su [Surgery];Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];aciclovir/dt [Drug Therapy];ganciclovir/dt [Drug Therapy];lactulose/ad [Drug Administration];lactulose/dt [Drug Therapy];mannitol/dt [Drug Therapy];neomycin/ad [Drug Administration];neomycin/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy],"Broue, P.;Mas, E.",2007,June,http://dx.doi.org/10.1016/j.arcped.2007.02.026,0,0,
1941,D-penicillamin-induced elastosis perforans serpiginosa. [French],,adult;article;atrophy;case report;clinical examination;Ehlers Danlos syndrome;elastic fiber;elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/dt [Drug Therapy];erythema;histopathology;human;keratinocyte;keratosis;male;Marfan syndrome;osteogenesis imperfecta;papule;pathophysiology;Rothmund Thomson syndrome;skin biopsy;skin disease/dt [Drug Therapy];skin disease/si [Side Effect];Wilson disease/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];corticosteroid/tp [Topical Drug Administration];elastin/ec [Endogenous Compound];isotretinoin/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tazarotene/dt [Drug Therapy],"Devilliere, M.;Ingen-Housz-Oro, S.;Weber, N.;Cordoliani, F.;Vignon-Pennamen, M. D.;Manciet, J. R.;Sigal-Grinberg, M.",2007,October,http://dx.doi.org/10.1016/S0151-9638%2807%2992548-X,0,0,
1942,Trace element transport in the mammary gland,"The mammary gland has a remarkable capacity to adapt to maternal deficiency or excess of iron, copper, and zinc and to homeostatically control milk concentrations of these essential nutrients. Similarly, it can regulate changes in concentrations of iron, copper, and zinc change during lactation. For iron, this regulation is achieved by transferrin receptor, DMT1, and ferroportin, whereas mammary gland copper metabolism is regulated by Ctr1, ATP7A, and ATP7B. Zinc homeostasis is complex, involving both zinc importers (Zip3) and zinc exporters (ZnT-1, ZnT-2, and ZnT-4). Both transcriptional and post-translational regulation can affect protein abundance and cellular localization of these transporters, finely orchestrating uptake, intracellular trafficking, and secretion of iron, copper, and zinc. The control of mammary gland uptake and milk secretion of iron, copper, and zinc protects both the mammary gland and the breast-fed infant against deficiency and excess of these nutrients. Copyright © 2007 by Annual Reviews. All rights reserved.",Copper;Copper transporters;Interactions;Iron;Iron transporters;Vitamin A;Zinc;Zinc transporters;breast milk;cell migration;copper deficiency;copper metabolism;homeostasis;human;iron deficiency/dt [Drug Therapy];iron metabolism;lactation;mammary gland;nonhuman;priority journal;protein binding;protein expression;protein localization;protein synthesis;regulatory mechanism;retinol deficiency;review;transcription regulation;translation regulation;unspecified side effect/si [Side Effect];Wilson disease;zinc deficiency;zinc metabolism;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];ferroportin/ec [Endogenous Compound];iron/ae [Adverse Drug Reaction];iron/dt [Drug Therapy];iron/ec [Endogenous Compound];iron/iv [Intravenous Drug Administration];lactoferrin/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];natural resistance associated macrophage protein 2/ec [Endogenous Compound];prolactin/ec [Endogenous Compound];protein zinc import protein 3/ec [Endogenous Compound];protein zinc transporter 1/ec [Endogenous Compound];protein zinc transporter 2/ec [Endogenous Compound];protein zinc transporter 4/ec [Endogenous Compound];transferrin receptor/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc/ec [Endogenous Compound];zinc transporter/ec [Endogenous Compound],"Lonnerdal, B.",2007,,http://dx.doi.org/10.1146/annurev.nutr.27.061406.093809,0,0,
1943,Wilson disease with visceral leishmaniasis: An extremely uncommon presentation,"Visceral leishmaniasis (VL), which is caused by the protozoa Leishmania donovani and transmitted by the bite of the female sand fly Phlebotomus argentipes, is common in Bihar, India. Wilson disease is an autosomal recessive disorder of copper metabolism in which copper is deposited in the brain and liver. We report a case of an extremely uncommon combination of these diseases in a patient. Treatment options for such a combination of diseases are limited and difficult. Copyright © 2007 by The American Society of Tropical Medicine and Hygiene.",adolescent;anamnesis;article;case report;clinical feature;drug dose increase;follow up;human;laboratory test;male;neurologic examination;visceral leishmaniasis/di [Diagnosis];visceral leishmaniasis/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];miltefosine/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];piperidine derivative/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];pyridoxine/po [Oral Drug Administration];triphenhexydyl/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Pandey, K.;Sinha, P. K.;Das, V. N. R.;Kumar, N.;Verma, N.;Bimal, S.;Lal, C. S.;Topno, R. K.;Singh, D.;Verma, R. B.;Bhattacharya, S. K.;Das, P.",2007,September,,0,0,
1944,Mild zinc deficiency and dietary phytic acid accelerates the development of fulminant hepatitis in LEC rats,"Background and Aim: Restriction of copper intake delays hepatic copper accumulation in Long-Evans Cinnamon (LEC) rats, which are animal models of Wilson's disease. Involvement of zinc is suggested to develop hepatitis in the disease; however, this has not been clarified. The aims of this study were to investigate the effects of mild zinc deficiency on the development of hepatitis and to determine the relationship between the absorption and hepatic levels of copper, zinc and iron. Methods: Male LEC and F344 (wild type atp7b) rats were fed a low zinc, phytate-containing or control diet. The onset of hepatitis (Experiment 1), and absorptive rates of copper, zinc and iron and hepatitis indices in 4 weeks (Experiment 2) were observed. Results: The onset of fulminant hepatitis in LEC rats was much earlier in the low zinc and phytate groups (mean 94.6 +/- 2.74 days and 82.8 +/- 3.56 days old, respectively) than in the control group (136 +/- 2.11 days old) with worse hepatitis indices. Hepatic copper levels were much higher in LEC rats than F344 rats, but were not largely different among the diet groups without prominent changes in copper absorption. Hepatic levels and intestinal absorption of zinc and iron were lower in the phytate group than in the control group. Conclusion: Mild zinc deficiencies caused by a low zinc or phytate-containing diet accelerate the onset of hepatitis in LEC rats without increasing copper absorption, and zinc and iron metabolism may be involved in the earlier onset of jaundice of LEC rats. © 2006 The Authors.",LEC rats;Metal absorption;Mild zinc deficiency;Phytic acid;Wilson's disease;animal experiment;animal model;animal tissue;article;controlled study;copper metabolism;hepatitis/et [Etiology];intestine absorption;iron absorption;liver level;Long Evans cinnamon rat;male;nonhuman;pathophysiology;priority journal;rat;Wilson disease/et [Etiology];zinc deficiency;zinc metabolism;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];phytic acid/to [Drug Toxicity];zinc/ec [Endogenous Compound],"Saito, A.;Nakayama, K.;Hara, H.",2007,February,http://dx.doi.org/10.1111/j.1440-1746.2006.04506.x,0,0,
1945,Possible role of zinc and iron in the development of hepatic abnormality in Long-Evans Cinnamon rats,,copper metabolism;editorial;hepatitis/et [Etiology];hepatitis/pc [Prevention];iron deficiency;liver cell carcinoma/et [Etiology];liver cell carcinoma/pc [Prevention];liver disease/et [Etiology];liver disease/pc [Prevention];liver injury;Long Evans cinnamon rat;mineral intake;nonhuman;pathophysiology;priority journal;Wilson disease/et [Etiology];Wilson disease/pc [Prevention];zinc deficiency/dt [Drug Therapy];iron/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];zinc/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration];zinc acetate/pd [Pharmacology],"Kasai, N.",2007,February,http://dx.doi.org/10.1111/j.1440-1746.2007.04856.x,0,0,
1946,The safety of pharmacological therapies for gastrointestinal conditions encountered during pregnancy,"Properly assessing the safety of pharmacological therapies for gastrointestinal conditions encountered during pregnancy is a challenge on account of both the often limited controlled data available and the potentially confounding effect of the underlying disorders requiring treatment on fetal outcomes. Here, the available data with regard to gastrointestinal disorders specific to pregnancy, those that may be precipitated or exacerbated by pregnancy and those that may be pre-existing or arise concurrently during pregnancy are reviewed. © 2007 Informa UK Ltd.",Gastrointestinal conditions;Pharmacological therapy;Pregnancy;absence of side effects/si [Side Effect];autoimmune hepatitis/co [Complication];autoimmune hepatitis/dt [Drug Therapy];birth defect/si [Side Effect];bradycardia/si [Side Effect];Budd Chiari syndrome/co [Complication];Budd Chiari syndrome/dt [Drug Therapy];cholestasis/dt [Drug Therapy];clinical trial;congenital malformation/et [Etiology];cutis laxa/si [Side Effect];drug megadose;endoscopic retrograde cholangiopancreatography;enteritis/co [Complication];enteritis/dt [Drug Therapy];fetus death;gastroesophageal reflux/co [Complication];gastroesophageal reflux/dt [Drug Therapy];gastrointestinal disease/co [Complication];gastrointestinal disease/dt [Drug Therapy];gastrointestinal disease/th [Therapy];HELLP syndrome/co [Complication];HELLP syndrome/dt [Drug Therapy];hepatitis B/co [Complication];hepatitis B/dt [Drug Therapy];hepatitis C/co [Complication];hepatitis C/dt [Drug Therapy];human;hypercalcemia/si [Side Effect];hyperemesis gravidarum/co [Complication];hyperemesis gravidarum/dt [Drug Therapy];hyperemesis gravidarum/th [Therapy];hypoglycemia/si [Side Effect];infantile hypotonia/si [Side Effect];irritable colon/co [Complication];irritable colon/dt [Drug Therapy];kidney dysfunction/si [Side Effect];liver fatty degeneration/co [Complication];liver fatty degeneration/dt [Drug Therapy];liver fatty degeneration/su [Surgery];liver fatty degeneration/th [Therapy];liver hematoma/co [Complication];liver transplantation;low birth weight/si [Side Effect];low drug dose;metabolic alkalosis/si [Side Effect];milk alkali syndrome/si [Side Effect];nausea and vomiting/co [Complication];nausea and vomiting/dt [Drug Therapy];nausea and vomiting/th [Therapy];nephrolithiasis/si [Side Effect];nonhuman;portal hypertension/co [Complication];portal hypertension/dt [Drug Therapy];portal hypertension/pc [Prevention];pregnancy complication/co [Complication];pregnancy complication/dt [Drug Therapy];pregnancy complication/th [Therapy];premature labor/si [Side Effect];prematurity/co [Complication];primary biliary cirrhosis/co [Complication];primary biliary cirrhosis/dt [Drug Therapy];rehydration;respiratory distress/si [Side Effect];review;risk assessment;small for date infant/si [Side Effect];teratogenicity;vitamin supplementation;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];aluminum magnesium hydroxide/ae [Adverse Drug Reaction];aluminum magnesium hydroxide/do [Drug Dose];aluminum magnesium hydroxide/dt [Drug Therapy];antacid agent/ae [Adverse Drug Reaction];antacid agent/do [Drug Dose];antacid agent/dt [Drug Therapy];azathioprine/dt [Drug Therapy];azathioprine/to [Drug Toxicity];cimetidine/ae [Adverse Drug Reaction];cimetidine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];cyclizine/ae [Adverse Drug Reaction];cyclizine/dt [Drug Therapy];cyclizine/to [Drug Toxicity];dixyrazine/ae [Adverse Drug Reaction];dixyrazine/dt [Drug Therapy];dixyrazine/to [Drug Toxicity];famotidine/dt [Drug Therapy];famotidine/to [Drug Toxicity];glucose;lamivudine/dt [Drug Therapy];lansoprazole/ae [Adverse Drug Reaction];lansoprazole/dt [Drug Therapy];lidocaine/ae [Adverse Drug Reaction];lidocaine/dt [Drug Therapy];loperamide/dt [Drug Therapy];loperamide/to [Drug Toxicity];magnesium trisilicate/ae [Adverse Drug Reaction];magnesium trisilicate/do [Drug Dose];magnesium trisilicate/dt [Drug Therapy];meclozine/ae [Adverse Drug Reaction];meclozine/dt [Drug Therapy];meclozine/to [Drug Toxicity];methotrexate/do [Drug Dose];methotrexate/dt [Drug Therapy];methotrexate/to [Drug Toxicity];metoclopramide/ae [Adverse Drug Reaction];metoclopramide/dt [Drug Therapy];metoclopramide/to [Drug Toxicity];mycophenolic acid 2 morpholinoethyl ester/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester/to [Drug Toxicity];omeprazole/dt [Drug Therapy];omeprazole/to [Drug Toxicity];ondansetron/ae [Adverse Drug Reaction];ondansetron/dt [Drug Therapy];ondansetron/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prochlorperazine/ae [Adverse Drug Reaction];prochlorperazine/dt [Drug Therapy];prochlorperazine/to [Drug Toxicity];promethazine/ae [Adverse Drug Reaction];promethazine/dt [Drug Therapy];promethazine/to [Drug Toxicity];propranolol/ae [Adverse Drug Reaction];propranolol/dt [Drug Therapy];tegaserod/ae [Adverse Drug Reaction];tegaserod/dt [Drug Therapy];thalidomide/do [Drug Dose];thalidomide/dt [Drug Therapy];thalidomide/to [Drug Toxicity];trimethobenzamide/ae [Adverse Drug Reaction];trimethobenzamide/dt [Drug Therapy];trimethobenzamide/to [Drug Toxicity];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];warfarin/dt [Drug Therapy];warfarin/to [Drug Toxicity],"Almeida, J. A.;Riordan, S. M.",2007,September,http://dx.doi.org/10.1517/14740338.6.5.493,0,0,
1947,Mania as the first manifestation of Wilson's disease,"Background: Although mental changes are frequent in Wilson's disease, severe psychiatric disorders occur uncommonly and usually accompany the neurological picture. There are few reports in the literature of Wilson's disease patients with typical bipolar affective disorder (BPAD). Case report: The authors report the case of a patient with Wilson's disease whose initial manifestation was a manic episode followed by depression. Tremor in the upper limbs appeared one year after the onset of symptoms. The diagnosis of Wilson's disease was established three years after the first symptoms appeared, based on the neuropsychiatric picture, the detection of Kayser-Fleischer rings and the results of diagnostic tests indicating chronic liver disease and copper excess. ATP7B genotyping and magnetic resonance imaging of the brain with proton spectroscopy study were also performed. The patient became asymptomatic two years after starting treatment with penicillamine and remained non-symptomatic controlled during the eight-year follow-up period, without any specific treatment for the BPAD. Conclusions: To our knowledge, this is a singular report of a case of Wilson's disease in which a manic episode preceded the onset of neurological symptoms. The association between Wilson's disease and bipolar disorder is discussed. © 2008 Blackwell Munksgaard.",Bipolar disorder;Wilson's disease;adult;aggressiveness;anamnesis;apathy;article;ataxia;behavior change;bilirubin blood level;case report;chronic liver disease/di [Diagnosis];drug dose increase;dysarthria;echography;grandiose delusion;human;laboratory test;limb tremor;liver biopsy;male;mania/dt [Drug Therapy];neurologic examination;nuclear magnetic resonance imaging;priority journal;restlessness/dt [Drug Therapy];slit lamp;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];haloperidol/dt [Drug Therapy];lithium/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Machado, A. C.;Deguti, M. M.;Caixeta, L.;Spitz, M.;Lucato, L. T.;Barbosa, E. R.",2008,May,http://dx.doi.org/10.1111/j.1399-5618.2007.00531.x,0,0,
1948,Metabolic liver disease in children,"The aim of this article is to provide essential information for hepatologists, who primarily care for adults, regarding liver-based inborn errors of metabolism with particular reference to those that may be treatable with liver transplantation and to provide adequate references for more in-depth study should one of these disease states be encountered. © 2008 AASLD.",alpha 1 antitrypsin deficiency/cn [Congenital Disorder];article;bile acid synthesis;blood transfusion;carbohydrate metabolism;cerebrotendinous xanthomatosis/cn [Congenital Disorder];chelation therapy;child;childhood disease/cn [Congenital Disorder];childhood disease/di [Diagnosis];childhood disease/dt [Drug Therapy];childhood disease/et [Etiology];childhood disease/pc [Prevention];childhood disease/su [Surgery];cholestasis;cholesterol ester storage disease/cn [Congenital Disorder];cholesterol ester storage disease/dt [Drug Therapy];chronic kidney disease;coronary artery disease/su [Surgery];Crigler Najjar syndrome/cn [Congenital Disorder];Crigler Najjar syndrome/dt [Drug Therapy];Crigler Najjar syndrome/su [Surgery];Crigler Najjar syndrome/th [Therapy];cystic fibrosis/cn [Congenital Disorder];diet restriction;disorders of amino acid and protein metabolism/cn [Congenital Disorder];disorders of amino acid and protein metabolism/dt [Drug Therapy];disorders of amino acid and protein metabolism/su [Surgery];disorders of amino acid and protein metabolism/th [Therapy];disorders of mitochondrial functions/cn [Congenital Disorder];disorders of mitochondrial functions/su [Surgery];erythropoietic protoporphyria/cn [Congenital Disorder];erythropoietic protoporphyria/dt [Drug Therapy];erythropoietic protoporphyria/su [Surgery];familial hypercholesterolemia/cn [Congenital Disorder];galactosemia/cn [Congenital Disorder];gene mutation;glycogen storage disease/cn [Congenital Disorder];glycogen storage disease type 1/cn [Congenital Disorder];glycogen storage disease type 3/cn [Congenital Disorder];glycogen storage disease type 4/cn [Congenital Disorder];hemochromatosis/cn [Congenital Disorder];hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/pc [Prevention];hemochromatosis/su [Surgery];hemodialysis;hereditary fructose intolerance/cn [Congenital Disorder];hereditary fructose intolerance/su [Surgery];hereditary fructose intolerance/th [Therapy];human;hyperammonemia/cn [Congenital Disorder];hyperammonemia/dt [Drug Therapy];hyperammonemia/su [Surgery];hyperammonemia/th [Therapy];inborn error of metabolism/cn [Congenital Disorder];inborn error of metabolism/di [Diagnosis];inborn error of metabolism/dt [Drug Therapy];inborn error of metabolism/et [Etiology];inborn error of metabolism/pc [Prevention];inborn error of metabolism/su [Surgery];intrahepatic cholestasis/cn [Congenital Disorder];intrahepatic cholestasis/dt [Drug Therapy];intrahepatic cholestasis/su [Surgery];kidney transplantation;liver cell carcinoma;liver cirrhosis;liver disease/cn [Congenital Disorder];liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/pc [Prevention];liver disease/su [Surgery];liver failure/su [Surgery];liver fibrosis/dt [Drug Therapy];liver transplantation;maple syrup urine disease/cn [Congenital Disorder];maple syrup urine disease/su [Surgery];maple syrup urine disease/th [Therapy];methylmalonic aciduria/cn [Congenital Disorder];methylmalonic aciduria/dt [Drug Therapy];neutropenia/dt [Drug Therapy];Niemann Pick disease/cn [Congenital Disorder];Niemann Pick disease/di [Diagnosis];Niemann Pick disease/su [Surgery];nonhuman;nuclear magnetic resonance spectroscopy;oxalosis 1/cn [Congenital Disorder];oxalosis 1/dt [Drug Therapy];oxalosis 1/th [Therapy];pathophysiology;photosensitivity;phototherapy;portal hypertension/dt [Drug Therapy];portal hypertension/su [Surgery];portosystemic anastomosis;priority journal;propionic acidemia/cn [Congenital Disorder];propionic acidemia/dt [Drug Therapy];propionic acidemia/th [Therapy];protein restriction;survival rate;tyrosinemia/cn [Congenital Disorder];tyrosinemia/dt [Drug Therapy];tyrosinemia/su [Surgery];urea cycle;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wolman disease/cn [Congenital Disorder];acetylcysteine/dt [Drug Therapy];alpha 1 antitrypsin/ec [Endogenous Compound];alpha tocopherol/dt [Drug Therapy];antioxidant/dt [Drug Therapy];arginine/dt [Drug Therapy];arginine/ec [Endogenous Compound];benzoic acid/dt [Drug Therapy];benzoic acid/iv [Intravenous Drug Administration];benzoic acid/po [Oral Drug Administration];beta adrenergic receptor blocking agent/dt [Drug Therapy];citrulline/dt [Drug Therapy];citrulline/ec [Endogenous Compound];colestyramine/dt [Drug Therapy];cyanocobalamin/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];essential amino acid/dt [Drug Therapy];granulocyte colony stimulating factor/dt [Drug Therapy];hemin/dt [Drug Therapy];hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy];immunoglobulin/dt [Drug Therapy];immunoglobulin/iv [Intravenous Drug Administration];mesoporphyrin/dt [Drug Therapy];nitisinone/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];phenylacetic acid/dt [Drug Therapy];phenylacetic acid/iv [Intravenous Drug Administration];phenylacetic acid/po [Oral Drug Administration];prostaglandin E1/dt [Drug Therapy];protoporphyrin tin/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];selenium/dt [Drug Therapy];tetrathiomolybdate ammonium/cb [Drug Combination];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];valproic acid;zinc derivative/cb [Drug Combination];zinc derivative/dt [Drug Therapy],"Hansen, K.;Horslen, S.",2008,April,http://dx.doi.org/10.1002/lt.21470,0,0,
1949,Inherited metabolic disease of the liver,"PURPOSE OF REVIEW: Elucidation of metabolic pathways for copper and iron improved our understanding of Wilson disease and genetic hemochromatosis. Some inherited liver diseases are now characterized by protein-folding mutations, including Gaucher disease, cystic fibrosis and ZZ alpha1-antitrypsin deficiency. Studies now focus on associations between glycogen storage disease, hepatic adenoma formation and transformation to hepatocellular carcinoma. Continued progress in the study of the diagnosis, natural history and treatment of inherited liver diseases is the subject of this review. RECENT FINDINGS: Further understanding of metabolic pathways for iron and copper have led to a search for factors that modify phenotypic expression of Wilson disease and genetic hemochromatosis. Hepcidin plays a key role in modulating iron uptake in iron-overload disorders and new studies elucidate hepcidin regulation. For glycogen storage diseases, studies on the natural history and hepatocellular transformation necessitate tumor surveillance and possible early transplantation. A better understanding of genetic and nongenetic modifiers in ZZ alpha1-antitrypsin deficiency and other disorders of protein misfolding will improve our ability to manage these patients. SUMMARY: Recent discoveries in iron, copper and glycogen metabolism advance our ability to diagnose and treat inherited metabolic diseases of the liver. Some of these important findings are detailed in this review. © 2008 Lippincott Williams & Wilkins, Inc.",alpha1-antitrypsin;atp7b;Glycogen storage disease;Hemochromatosis;Hepcidin;Wilson disease;alpha antitrypsin deficiency/et [Etiology];alpha antitrypsin deficiency/th [Therapy];copper metabolism;cystic fibrosis;disease association;early intervention;enzyme replacement;Gaucher disease/et [Etiology];gene mutation;genetics;glycogen metabolism;glycogen storage disease/et [Etiology];hemochromatosis/dt [Drug Therapy];hemochromatosis/et [Etiology];human;iron metabolism;iron overload/dt [Drug Therapy];iron overload/et [Etiology];iron transport;liver adenoma/et [Etiology];liver cell carcinoma/et [Etiology];liver metabolism;liver transplantation;malignant transformation;metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];modulation;nonhuman;phenotype;plasmapheresis;protein folding;protein function;review;viral gene therapy;Wilson disease/et [Etiology];adenovirus vector;bone morphogenetic protein 2/dt [Drug Therapy];bone morphogenetic protein 2/pd [Pharmacology];copper/ec [Endogenous Compound];deferiprone/cb [Drug Combination];deferiprone/dt [Drug Therapy];deferoxamine/cb [Drug Combination];deferoxamine/dt [Drug Therapy];glycogen/ec [Endogenous Compound];hepcidin/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Taddei, T.;Mistry, P.;Schilsky, M. L.",2008,May,http://dx.doi.org/10.1097/MOG.0b013e3282fcbc0f,0,0,
1950,Consensus recommendations for managing asymptomatic persistent non-virus non-alcohol related elevation of aminotransferase levels. Suggestions for diagnostic procedures and monitoring,"A persistent increase in non-virus non-alcohol related aminostransferase levels can have multiple causes, which differ in terms of prevalence and clinical importance. In the general population, the most frequent cause is non-alcoholic hepatic steatosis, which can evolve into steato-hepatitis and cirrhosis. The treatment for steatosis and non-alcoholic steato-hepatitis consists of modifying lifestyles, whereas the effectiveness of drug treatment remains to be determined. Other much less frequent (yet not rare) causes of persistent non-virus non-alcohol related elevations in aminotransferase levels are celiac disease and hemochromatosis, whereas autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and alpha-1-anti-trypsin deficit are rare. Given that some of these conditions are susceptible to treatment, early diagnosis is important. No epidemiological data are available for evaluating the prevalence of elevated aminotransferase levels correlated with the toxicity of drugs or other xenobiotics, including herbal products. The present document, created by a panel of experts based on a systematic review of scientific evidence, is mainly geared towards physicians working in General Medicine and Transfusion Centres, who generally represent the first contact of persons with elevated aminotransferase levels. The document includes suggestions for diagnosing causes of persistent non-virus non-alcohol related increases in aminotransferase levels, considering the frequency and response to treatment. The conditions requiring specialized visits are also indicated. © 2008 Editrice Gastroenterologica Italiana S.r.l.",Aminotransferases elevation;Asymptomatic;Liver diseases;Non-alcohol;Non-virus;alanine aminotransferase blood level;alcohol liver disease/si [Side Effect];alpha 1 antitrypsin deficiency/di [Diagnosis];aminotransferase blood level;article;aspartate aminotransferase blood level;autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];autoimmune hepatitis/si [Side Effect];celiac disease/di [Diagnosis];celiac disease/th [Therapy];clinical trial;cytapheresis;diagnostic accuracy;diagnostic procedure;evidence based medicine;general practice;gluten free diet;granulomatous hepatitis/si [Side Effect];hemochromatosis/di [Diagnosis];hemochromatosis/th [Therapy];human;laboratory test;lifestyle modification;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/th [Therapy];nonalcoholic fatty liver/di [Diagnosis];nonalcoholic fatty liver/th [Therapy];primary biliary cirrhosis/di [Diagnosis];primary sclerosing cholangitis/di [Diagnosis];reference value;sensitivity and specificity;side effect/si [Side Effect];systematic review;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];amiodarone/ae [Adverse Drug Reaction];aspartate aminotransferase/ec [Endogenous Compound];carbamazepine/ae [Adverse Drug Reaction];chelate/dt [Drug Therapy];copper/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];methyldopa/ae [Adverse Drug Reaction];nitrofurantoin/ae [Adverse Drug Reaction];phenylbutazone/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy],"Morisco, F.;Pagliaro, L.;Caporaso, N.;Bianco, E.;Sagliocca, L.;Fargion, S.;Smedile, A.;Salvagnini, M.;Mele, A.",2008,July,http://dx.doi.org/10.1016/j.dld.2008.02.003,0,0,
1951,Value of molecular analysis of Wilson's disease in the absence of tissue copper deposits: A novel ATP<inf>7</inf>B mutation in an adult patient,"Wilson's disease (WD) is a disorder of copper metabolism leading to copper accumulation in the liver and in extrahepatic organs, such as brain and cornea. We present a patient with liver disease who did not fulfil the biochemical criteria for WD. Mutational analysis was necessary to make the diagnosis and show a new mutation. Our case supports the use of mutation analysis in cases with unclear liver disease and suggests that the spectrum of WD is broader than currently assumed. © 2008 Van Zuiden Communications B.V. All rights reserved.",Copper;Hepatitis;Mutation analysis;Wilson's disease;adult;alanine aminotransferase blood level;anamnesis;article;aspartate aminotransferase blood level;case report;ceruloplasmin blood level;chelation therapy;clinical feature;copper metabolism;drug response;enzyme blood level;fatty liver/di [Diagnosis];female;frameshift mutation;gene mutation;gene sequence;hepatitis/di [Diagnosis];heterozygosity;human;liver biopsy;liver disease;liver fibrosis/di [Diagnosis];molecular genetics;mutational analysis;scoring system;sequence analysis;tissue level;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cytosine/ec [Endogenous Compound];liver enzyme/ec [Endogenous Compound];thymine/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy],"Kok, K. F.;Hoevenaars, B.;Waanders, E.;Drenth, J. P. H.",2008,September,,0,0,
1952,Copper: Two sides of the same coin,,apoptosis;cell level;ceruloplasmin blood level;chelation;clinical effectiveness;connective tissue disease;copper blood level;copper deficiency;copper metabolism;Descemet membrane;differential diagnosis;disease carrier;disease course;disease severity;drug safety;editorial;enzyme inhibition;epithelium cell;gene mutation;genetic analysis;hemolysis;human;inborn error of metabolism;liver cell;liver failure/co [Complication];liver level;liver transplantation;Menkes syndrome/et [Etiology];mitochondrial membrane;mitochondrial respiration;molecular genetics;neurologic disease;nonhuman;obstructive jaundice;oxidative stress;promoter region;risk reduction;scoring system;small intestine mucosa;symptomatology;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];amitriptyline/dt [Drug Therapy];amitriptyline/pd [Pharmacology];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];dopamine beta monooxygenase/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];sphingomyelin phosphodiesterase/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];trace element;trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Houwen, R. H. J.",2008,September,,0,0,
1953,The study of bone metabolism and current treatment of hepatolenticular degeneration. [Chinese],,bone metabolism;human;review;Wilson disease/dt [Drug Therapy];calcitonin/dt [Drug Therapy];cyclosporin A/dt [Drug Therapy];estrogen/ec [Endogenous Compound];growth hormone/ec [Endogenous Compound];osteoprotegerin/ec [Endogenous Compound];parathyroid hormone/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Yang, G. E.;Wang, X.;Yang, R. M.",2008,April,,0,0,
1954,Liver fibrosis,"Liver damage leads to an inflammatory response and to the activation and proliferation of mesenchymal cell populations within the liver which remodel the extracellular matrix as part of an orchestrated wound-healing response. Chronic damage results in a progressive accumulation of scarring proteins (fibrosis) that, with increasing severity, alters tissue structure and function, leading to cirrhosis and liver failure. Efforts to modulate the fibrogenesis process have focused on understanding the biology of the heterogeneous liver fibroblast populations. The fibroblasts are derived from sources within and outwith the liver. Fibroblasts expressing alpha-smooth muscle actin (myofibroblasts) may be derived from the transdifferentiation of quiescent hepatic stellate cells. Other fibroblasts emerge from the portal tracts within the liver. At least a proportion of these cells in diseased liver originate from the bone marrow. In addition, fibrogenic fibroblasts may also be generated through liver epithelial (hepatocyte and biliary epithelial cell)-mesenchymal transition. Whatever their origin, it is clear that fibrogenic fibroblast activity is sensitive to (and may be active in) the cytokine and chemokine profiles of liver-resident leucocytes such as macrophages. They may also be a component driving the regeneration of tissue. Understanding the complex intercellular interactions regulating liver fibrogenesis is of increasing importance in view of predicted increases in chronic liver disease and the current paucity of effective therapies. © The Authors.",Fibroblast;Fibrosis;Hepatocyte;Kupffer cell;Myofibroblast;Stellate cell;alcohol abstinence;alcohol liver cirrhosis;autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];bone marrow cell;Budd Chiari syndrome/di [Diagnosis];cell differentiation;cell function;cell proliferation;cell type;cholelithiasis/di [Diagnosis];cholelithiasis/su [Surgery];clinical trial;cystic fibrosis/di [Diagnosis];cystic fibrosis/dt [Drug Therapy];delta agent hepatitis/dt [Drug Therapy];diagnostic procedure;disease severity;exercise;hemochromatosis/di [Diagnosis];hemochromatosis/su [Surgery];hepatitis;hepatitis B/di [Diagnosis];hepatitis C/di [Diagnosis];human;leukocyte;liver cirrhosis;liver failure;liver fibrosis/dt [Drug Therapy];liver toxicity;macrophage;mesenchyme cell;non insulin dependent diabetes mellitus/dt [Drug Therapy];nonalcoholic fatty liver/di [Diagnosis];nonhuman;partial hepatectomy;phlebotomy;primary biliary cirrhosis/di [Diagnosis];primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/di [Diagnosis];priority journal;review;weight reduction;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];6 ethylchenodeoxycholic acid/ct [Clinical Trial];6 ethylchenodeoxycholic acid/dt [Drug Therapy];6 ethylchenodeoxycholic acid/pd [Pharmacology];alpha interferon/dt [Drug Therapy];alpha smooth muscle actin/ec [Endogenous Compound];biguanide derivative/dt [Drug Therapy];chemokine;chenodeoxycholic acid derivative/ct [Clinical Trial];chenodeoxycholic acid derivative/dt [Drug Therapy];chenodeoxycholic acid derivative/pd [Pharmacology];cyclosporin A/ct [Clinical Trial];cyclosporin A/cm [Drug Comparison];cyclosporin A/dt [Drug Therapy];cyclosporin A/pd [Pharmacology];cytokine;farglitazar/ct [Clinical Trial];farglitazar/dt [Drug Therapy];farglitazar/pd [Pharmacology];gamma interferon/pd [Pharmacology];gamma1b interferon/ct [Clinical Trial];gamma1b interferon/dt [Drug Therapy];gamma1b interferon/pd [Pharmacology];glucocorticoid/dt [Drug Therapy];hepatitis B vaccine/dt [Drug Therapy];int 747;interleukin 10/pd [Pharmacology];interleukin 6/pd [Pharmacology];irbesartan/ct [Clinical Trial];irbesartan/dt [Drug Therapy];irbesartan/pd [Pharmacology];metformin/dt [Drug Therapy];nucleoside derivative/dt [Drug Therapy];peginterferon alpha/dt [Drug Therapy];peginterferon alpha2a/ct [Clinical Trial];peginterferon alpha2a/dt [Drug Therapy];peginterferon alpha2a/pd [Pharmacology];peginterferon alpha2b/ct [Clinical Trial];peginterferon alpha2b/dt [Drug Therapy];peginterferon alpha2b/pd [Pharmacology];penicillamine/dt [Drug Therapy];pentoxifylline/ct [Clinical Trial];pentoxifylline/dt [Drug Therapy];pentoxifylline/pd [Pharmacology];pioglitazone/dt [Drug Therapy];pirfenidone/ct [Clinical Trial];pirfenidone/dt [Drug Therapy];pirfenidone/pd [Pharmacology];tacrolimus/cm [Drug Comparison];tumor necrosis factor alpha;unclassified drug;ursodeoxycholic acid/dt [Drug Therapy];warfarin/ct [Clinical Trial];warfarin/dt [Drug Therapy];warfarin/pd [Pharmacology],"Wallace, K.;Burt, A. D.;Wright, M. C.",2008,01 Apr,http://dx.doi.org/10.1042/BJ20071570,0,0,
1955,Single pass albumin dialysis (SPAD) in fulminant Wilsonian liver failure: A case report,"Since fulminant Wilsonian liver failure has an extremely poor prognosis, the use of a liver support system that can bridge patients to liver transplant is life saving. We report here the case of a 17-year-old female who presented with fulminant Wilsonian liver failure and intravascular hemolysis. With the subsequent development of encephalopathy and oliguria, single pass albumin dialysis (SPAD) was initiated for 5 days to augment copper removal. Continuous venovenous hemodialysis (CVVHD) was performed using the PRISMA machine, with a blood flow of 100 ml/min and a dialysate flow of 2 L/h for 8 h, then 1 L/ h. A 5% albumin dialysate was made by exchanging 1 L of 25% albumin for 1 L of Hemosol BO in a 5-L bag. Single pass albumin dialysis resulted in reductions in serum copper (154 to 59 mug/dL), conjugated bilirubin (37 to 23 mg/dL), lactate dehydrogenase (1305 to 729 units/L), and creatinine (1.1 to 0.9 mg/dL) as well as reduced blood transfusion requirements. Cessation of SPAD was followed by three plasmapheresis treatments for further copper removal. We conclude that SPAD is potentially an effective treatment in fulminant Wilson disease with hemolysis but that it should be used in combination with chelation to optimize the removal of copper. © IPNA 2008.",Albumin dialysis;Artificial liver support;Continuous venovenous hemodialysis;Fulminant liver failure;Single pass albumin dialysis (SPAD);Wilson disease;adolescent;article;bilirubin blood level;blood flow velocity;blood transfusion;brain disease;cadaver donor;case report;chelation therapy;continuous hemodialysis;copper blood level;creatinine blood level;dialysis;female;human;intravascular hemolysis/th [Therapy];lactate dehydrogenase blood level;liver failure/co [Complication];liver failure/su [Surgery];liver failure/th [Therapy];liver transplantation;oliguria;plasmapheresis;priority journal;single pass albumin dialysis;albumin;bilirubin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];trientine/po [Oral Drug Administration],"Collins, K. L.;Roberts, E. A.;Adeli, K.;Bohn, D.;Harvey, E. A.",2008,June,http://dx.doi.org/10.1007/s00467-008-0761-x,0,0,
1956,Do cytokines have any role in Wilson's disease?,"The aim of this study was to determine the serum cytokine levels in patients with Wilson's disease (WD) and correlate with phenotype, therapeutic status and laboratory data. In this cross-sectional study, the serum levels of cytokines were estimated in 34 patients (M : F, 23 : 11; drug-naive, 11) with WD (mean age: 13.8 +/- 8.6 and 19.6 +/- 9.03 years) and compared with 30 controls. The following serum cytokines were analysed using enzyme-linked immunosorbent assay: (i) tumour necrosis factor (TNF)-alpha, (ii) interferon (IFN)-gamma, (iii) interleukin (IL)-2, (iv) IL-6 and (v) IL-4. Serum TNF-alpha (P < 0.001), IFN-gamma (P = 0.005) and IL-6 (P < 0.001) were detectable in WD compared with controls. However, serum level elevation of IL-4 (P = 0.49) and IL-2 (P = 0.11), although detectable compared with controls, was statistically insignificant. The disease severity and therapeutic status did not affect the cytokines. Presence of anaemia, leucopenia, thrombocytopenia, pancytopenia and hepatic dysfunction did not influence cytokine levels. There was a significant negative correlation between IL-6 and ceruloplasmin (P = 0.04) and anti-inflammatory cytokines (IL-4) and copper level (P = 0.01). Serum cytokines, both proinflammatory and anti-inflammatory subtypes, were elevated significantly in patients with WD. Further studies would establish their role in its pathogenesis. © 2008 British Society for Immunology.",Cytokine;Pathogenesis of Wilson's disease;Wilson's disease;adolescent;adult;anemia;article;clinical article;controlled study;disease severity;enzyme linked immunosorbent assay;female;human;laboratory test;leukopenia;liver dysfunction;male;pancytopenia;phenotype;priority journal;protein blood level;protein function;scoring system;thrombocytopenia;Wilson disease/dt [Drug Therapy];cytokine/ec [Endogenous Compound];gamma interferon/ec [Endogenous Compound];interleukin 2/ec [Endogenous Compound];interleukin 4/ec [Endogenous Compound];interleukin 6/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tumor necrosis factor alpha/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy],"Goyal, M. K.;Sinha, S.;Patil, S. A.;Jayalekshmy, V.;Taly, A. B.",2008,October,http://dx.doi.org/10.1111/j.1365-2249.2008.03755.x,0,0,
1957,Evaluation of the Unified Wilson's Disease Rating Scale (UWDRS) in German patients with treated Wilson's disease,"Wilson's disease (WD) is an inherited autosomal-recessive disorder of copper metabolism characterized by a wide variety of neurological, hepatic, and psychiatric symptoms. The aim of the present study was the development and evaluation of a clinical rating scale, termed Unified Wilson's Disease Rating Scale (UWDRS), to assess the whole spectrum of clinical symptoms in WD. Altogether 107 patients (mean age 37.6 +/- 11.9 years; 46 male, 61 female) with treated WD participated in the study. Cronbach's alpha as a measure of the internal consistency for the entire scale was 0.92, whereas the intraclass correlation coefficient (ICC) was 0.98 (confidence interval (CI<inf>95%</inf>) 0.97-0.99), indicating an excellent interrater reliability as determined in 32 patients. Besides the total score was significantly correlated with the earning capacity of the patients as indicated by an estimated Spearman's rho = 0.54 (CI<inf>95%</inf> 0.40-0.69, P < 0.001). In summary, the UWDRS appears to be a promising tool to assess the disease severity in WD. Its usefulness in clinical research and drug trials should be further addressed. © 2007 Movement Disorder Society.",Clinical assessment;EuroWilson;GeNeMove;Rating scale;Wilson's disease;adult;article;combination chemotherapy;disease severity;factorial analysis;female;human;interrater reliability;major clinical study;male;monotherapy;osteoporosis;priority journal;symptom;validity;Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Leinweber, B.;Moller, J. C.;Scherag, A.;Reuner, U.;Gunther, P.;Lang, C. J. G.;Schmidt, H. H. J.;Schrader, C.;Bandmann, O.;Czlonkowska, A.;Oertel, W. H.;Hefter, H.",2008,15 Jan,http://dx.doi.org/10.1002/mds.21761,0,0,
1958,Wilson disease - Update on pathophysiology and management,"Wilson disease is an autosomal recessive inherited disorder of human copper metabolism that leads to neurological symptoms and hepatic damage of variable degree. The affected gene, ATP7B, encodes a hepatic copper-transporting protein, which plays a key role in human copper metabolism. Clinical symptoms are divided in neurological symptoms such as tremor, dysarthria, psychiatric disorders etc.; predominant hepatic disease or mixed presentations. Copper deposition in the liver may result in acute liver failure, chronic hepatitis or liver cirrhosis. Early recognition by means of clinical, biochemical or genetic examination and early initiation of therapy with chelators or zinc salts are essential for favourable outcome and prognosis. Liver transplantation is an alternative in cases with acute and chronic liver failure and cures the hepatic disease. Frequent monitoring of drug therapy, adverse effects, and compliance is critical for the prognosis of the disease.",atp7b;Central nervous system;Copper;Liver;Toxicity;anemia/si [Side Effect];autoimmune disease/si [Side Effect];ceruloplasmin blood level;chromosome 13;chronic hepatitis;computer assisted tomography;copper metabolism;Descemet membrane;diet therapy;drug dose reduction;drug monitoring;drug toxicity;dysarthria;dyspepsia/si [Side Effect];echography;fetus risk;gene mutation;gene therapy;genetic screening;genetics;health survey;human;inheritance;liver disease;liver failure/dt [Drug Therapy];liver transplantation;maintenance therapy;nephrotic syndrome/si [Side Effect];neurologic disease/si [Side Effect];nuclear magnetic resonance imaging;pathogenesis;pathophysiology;pregnancy;prognosis;review;scoring system;screening;side effect/si [Side Effect];stem cell transplantation;teratogenicity/si [Side Effect];treatment outcome;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];alpha tocopherol/dt [Drug Therapy];antioxidant;ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];Menkes protein/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];trientine/pd [Pharmacology];Wilson disease protein/ec [Endogenous Compound];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/do [Drug Dose];zinc derivative/dt [Drug Therapy],"Huster, D.;Leonhardt, K.;Mossner, J.",2008,,,0,0,
1959,Cystic White-Matter Changes in Childhood Wilson's Disease,"Altered signals in magnetic resonance imaging are present in most symptomatic patients with neurologic manifestations of Wilson's disease. The changes primarily involve the basal ganglia, but they can be diverse and can involve a host of other structures. We describe a 12-year-old boy with Wilson's disease who manifested prominent white-matter cystic changes. These changes can cause diagnostic confusion, and may also present prognostic implications. © 2008 Elsevier Inc. All rights reserved.",article;body posture;brain cyst;case report;ceruloplasmin blood level;disease exacerbation;drug withdrawal;dysarthria;dysgraphia;dystonia;follow up;human;hypersalivation;male;mutational analysis;neuroimaging;nuclear magnetic resonance imaging;priority journal;prognosis;recurrent disease;rigidity;school child;slit lamp;treatment outcome;urinary excretion;white matter;Wilson disease/dt [Drug Therapy];benzene derivative/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];trichlorohexiphenydyl/cb [Drug Combination];trichlorohexiphenydyl/dt [Drug Therapy];unclassified drug;zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Sankhyan, N.;Sharma, S.;Kalra, V.;Garg, A.;Balkrishnan, P.",2008,October,http://dx.doi.org/10.1016/j.pediatrneurol.2008.07.010,0,0,
1960,Liver Transplantation for Wilson's Disease,"Wilson's disease is an inherited disorder of copper metabolism characterized by reduced biliary copper excretion, which results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplantation (OLT) can be lifesaving for patients with Wilson's disease who present with fulminant liver failure and for patients' unresponsive to medical therapy. The aim of this study was to review our experience with OLT for patients with Wilson's disease. Between September 2001 and April 2007, 25 OLTs were performed in 24 patients (7 females and 17 males) with Wilson's disease of mean age 15.6 +/- 9.9 years (range, 5-51 years). Six patients underwent transplantation owing to coexistent fulminant hepatic failure and 18 with chronic advanced liver disease with (n = 8) or without (n = 10) associated neurologic manifestations. We performed 3 full-size, deceased-donor OLTs and 22 living-related donor OLTs. Eight patients had a family history of Wilson's disease. We detected a Kayser-Fleischer ring in 18 patients. All patients had a low serum ceruloplasmin level (mean, 27.8 mg/dL) and a high urinary copper excretion level (mean, 4119 mug/d) before OLT. Following successful OLT, there was a significant reduction in urinary copper excretion (median, 37.1 mug/d) in all patients. Mean follow-up was 21.7 +/- 19.8 months (range, 2-60 months). Retransplantation was required in 1 patient at 12 days after the first OLT owing to primary graft nonfunction. Five of the 24 patients died within 4 months of the surgery. The remaining 19 survivors (79%) have remained well, with normal liver function and no disease recurrence. In conclusion, OLT was a curative procedure for Wilson's disease among patients presenting with fulminant hepatic failure and others with end-stage hepatic insufficiency. After OLT, the serum ceruloplasmin level increased to the normal range, urinary copper excretion decreased, and neurologic manifestations improved. © 2008 Elsevier Inc. All rights reserved.",adolescent;adult;article;ceruloplasmin blood level;child;clinical article;controlled study;drug dose reduction;female;follow up;human;immunotherapy;liver disease;liver failure;liver function;liver transplantation;living donor;male;priority journal;treatment outcome;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];methylprednisolone/do [Drug Dose];penicillamine/dt [Drug Therapy];tacrolimus/cr [Drug Concentration],"Sevmis, S.;Karakayali, H.;Aliosmanoglu, I.;Yilmaz, U.;Ozcay, F.;Torgay, A.;Arslan, G.;Haberal, M.",2008,January 2008/February,http://dx.doi.org/10.1016/j.transproceed.2007.11.007,0,0,
1961,Transcranial magnetic stimulation in child neurology: Current and future directions,"Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation based on the principle of electromagnetic induction, where small intracranial electric currents are generated by a powerful, rapidly changing extracranial magnetic field. Over the past 2 decades TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults, but has been used on a more limited basis in children. We reviewed the literature to identify potential diagnostic and therapeutic applications of TMS in child neurology and also its safety in pediatrics. Although TMS has not been associated with any serious side effects in children and appears to be well tolerated, general safety guidelines should be established. The potential for applications of TMS in child neurology and psychiatry is significant. Given its excellent safety profile and possible therapeutic effect, this technique should develop as an important tool in pediatric neurology over the next decade. © 2008 SAGE Publications.",Cortical excitability;Cortical plasticity;Cortical reorganization;Corticospinal abnormalities;Corticospinal pathway maturation;Transcranial magnetic stimulation;brain depth stimulation;brain injury;cerebrovascular accident/th [Therapy];child;child health;child safety;differential diagnosis;epilepsy/dt [Drug Therapy];epilepsy/th [Therapy];evoked muscle response;human;mental disease/th [Therapy];motor dysfunction/di [Diagnosis];nerve cell differentiation;neuroimaging;neurologic disease/di [Diagnosis];neurophysiology;priority journal;pyramidal sign/di [Diagnosis];pyramidal tract;review;spasticity/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];anticonvulsive agent/dt [Drug Therapy];baclofen/dt [Drug Therapy];baclofen/tl [Intrathecal Drug Administration];penicillamine/dt [Drug Therapy],"Frye, R. E.;Rotenberg, A.;Ousley, M.;Pascual-Leone, A.",2008,January,http://dx.doi.org/10.1177/0883073807307972,0,0,
1962,Biomarkers of copper status: A brief update,"The essentiality of copper (Cu) in humans is demonstrated by various clinical features associated with deficiency, such as anaemia, hypercholesterolaemia and bone malformations. Despite significant effort over several decades a sensitive and specific Cu status biomarker has yet to be identified. The present article updates a comprehensive review recently published by the authors which assesses the reliability and robustness of current biomarkers and outlines the on-going search for novel indicators of status. The essential features of this earlier review are reiterated whilst considering whether there are other approaches, not yet tested, which may provide valuable information in the quest for an appropriate measure of copper status. Current biomarkers include a range of cuproenzymes such as the acute phase protein caeruloplasmin and Cu-Zn-superoxide dismutase all of which are influenced by a range of other dietary and environmental factors. A recent development is the identification of the Cu chaperone, CCS as a potential biomarker; although its reliability has yet to be established. This appears to be the most promising potential biomarker, responding to both Cu deficiency and excess. The potential for identifying a 'suite' of biomarkers using high-throughput technologies such as transcriptomics and proteomics is only now being examined. A combination of these technologies in conjunction with a range of innovative metal detection techniques is essential if the search for robust copper biomarkers is to be successful. © The Authors 2008.",Biomarkers;Copper deficiency;Copper excess;Copper status;anemia;article;bone malformation;bone metabolism;clinical feature;copper deficiency/di [Diagnosis];high throughput screening;human;hypercholesterolemia;Menkes syndrome;nonhuman;nutritional status;osteoporosis;proteomics;reliability;sensitivity and specificity;transcriptomics;Wilson disease;biological marker/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];pyridinoline/ec [Endogenous Compound],"Harvey, L. J.;McArdle, H. J.",2008,June,http://dx.doi.org/10.1017/S0007114508006806,0,0,
1963,Orphan Drug Act passes quarter-century milestone in fight against rare diseases,,animal experiment;animal model;child;childhood disease/di [Diagnosis];Crohn disease;drug approval;drug industry;drug legislation;drug marketing;drug research;food and drug administration;hairy cell leukemia/dt [Drug Therapy];human;nonhuman;note;priority journal;pseudoxanthoma elasticum/di [Diagnosis];rare disease/di [Diagnosis];rare disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];cladribine/dt [Drug Therapy];orphan drug/dv [Drug Development];orphan drug/pe [Pharmacoeconomics];zinc acetate/dt [Drug Therapy],"Lavine, G.",2008,01 Jul,http://dx.doi.org/10.2146/news080054,0,0,
1964,Wilson's disease: A rare thought present condition. [Spanish],,aminotransferase blood level;anemia/co [Complication];autosomal disorder;cardiovascular risk;clinical feature;copper blood level;cytotoxicity;diagnostic accuracy;dysarthria/co [Complication];dystonia/co [Complication];editorial;gene mutation;genetic disorder;gynecomastia/co [Complication];hepatitis/co [Complication];human;hypergammaglobulinemia;hypoparathyroidism/co [Complication];hypoproteinemia/co [Complication];kayser fleischer ring;lipid peroxidation;liver cell carcinoma/co [Complication];liver cirrhosis/co [Complication];liver dysfunction/co [Complication];liver graft;neurologic disease/co [Complication];protein expression;protein transport;tremor/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];X chromosome;aminotransferase/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Solis Munoz, P.;Solis Herruzo, J. A.",2008,August,,0,0,
1965,"Clinical presentation, diagnosis, and long-term outcome of 29 patients with Wilson's disease. [Spanish]","Objective: to analyze the clinical characteristics, treatment, and follow-up of a cohort of 29 patients with Wilson's disease (WD) within the region of Murcia. Patients and method: we reviewed the medical records of 29 cases of WD (mean age, 20.3 +/- 13.4 years) diagnosed during the last 16 years. Results: the most frequent reason for consultation was upon discovering a high transaminase level in almost half the patients, followed by tremors or dystonia in 17% of patients, respectively. A Kayser-Fleischer ring was observed in 17/29 (58.6%) of patients (100% of patients with pure neurological involvement and 35% of patients with pure clinical hepatic disease; p < 0.001). Blood copper levels not associated with ceruloplasmin as well as cupruria were notably superior in patients with neurological symptoms and in those with liver cirrhosis at the time of diagnosis. Patient clinical symptoms remained stable with D-penicillamine or trientine, or improved during the observation period, for 18 out of 29 patients (62%), while 11 out of 29 patients (38%) got worse. Conclusions: in our region patients with WD are diagnosed at a younger age, and in most cases for hepatic disease. Patients with neurological disease o liver cirrhosis had a high level of free copper not associated to ceruloplasmin and cupruria. The disease had a favorable evolution in all patients but those diagnosed with hepatic disease or advanced neurological disease. Copyright © 2008 Aran Ediciones, S. L.",Clinical presentation;Copper;Long-term outcome;Wilson's disease;adult;aminotransferase blood level;article;ceruloplasmin blood level;clinical article;clinical feature;cohort analysis;consultation;copper blood level;cupruria/co [Complication];drug dose reduction;drug withdrawal;dystonia/co [Complication];female;follow up;human;human tissue;kayser fleischer ring/co [Complication];laboratory test;liver cirrhosis/co [Complication];liver cirrhosis/su [Surgery];liver disease/co [Complication];male;medical record review;neurologic disease/co [Complication];polyarthritis/si [Side Effect];rash/si [Side Effect];tremor/co [Complication];weakness/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];acexamate zinc/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Rodrigo Agudo, J. L.;Valdes Mas, M.;Vargas Acosta, A. M.;Ortiz Sanchez, M. L.;Gil Del Castillo, M. L.;Carballo Alvarez, L. F.;Pons Minano, J. A.",2008,August,,0,1,
1966,Wilson's disease in paediatric age: Diagnosis and treatment. Recent advances. [Italian],"Wilson's disease is an autosomal-recessive disorder caused by mutation in the ATP7B gene, with resultant impairment of biliary excretion of copper. Subsequent copper accumulation, first in the liver but ultimately in the brain and other tissues, produces clinical manifestations that may include hepatic, neurological, psychiatric, ophthalmological, and other derangements. This article discusses the recent progress in diagnosis and treatment of this disease in paediatric age.",Wilson's disease;ATP7B gene;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/et [Etiology];biliary excretion;childhood disease/di [Diagnosis];childhood disease/dt [Drug Therapy];childhood disease/et [Etiology];clinical feature;diagnostic procedure;gene;gene mutation;human;review;treatment indication;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper;penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];sulfadiazine zinc/dt [Drug Therapy];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration],"Palumbo, E.",2008,November,,0,0,
1967,Epilepsy in inherited metabolic disorders,"Introduction: The study of neurometabolic diseases is still in a prolonged preliminary stage. The catalogue of these diseases continues to grow; some known clinical syndromes have been subdivided into a number of variants once the genes that cause them have been identified, and at the same time new metabolic disorders have been discovered that aggravate or contribute to forms of epilepsy not previously classified as cerebral metabolic disorders. Results: This review presents the basic principles underlying the recognition and treatment of epilepsy caused by neurometabolic diseases. These disorders are divided (purely for the sake of convenience) into epilepsy presenting in newborn infants, children, and adolescents and adults, recognizing that there is a significant degree of overlap between these chronological stages. Current analytical methods and therapeutic approaches are summarized both from a general point of view and within the context of each clinical syndrome, acknowledging that each patient presents specific peculiarities and that, in general, antiepileptic drugs provide few benefits compared with more specific types of therapy (eg, special diets or vitamins) when indicated. We also include therapeutic recommendations and a general approach to fulminant epilepsies of neurometabolic origin, emphasizing the importance of identifying all of the proband's relatives who may be potential carriers of a genetic disorder during the diagnostic and genetic counselling process. Particular emphasis is placed on disorders for which there is curative treatment and on the importance of follow-up by expert professionals. Conclusion: It is expected that in a few years' time it will be possible to know the metabolomic profile of these diseases (possibly by non-invasive methods), thus facilitating accurate diagnosis and making it possible to establish the response to treatment and to identify all individuals who are carriers or remain minimally symptomatic in terms of their risk of manifesting or transmitting epilepsy. Copyright © 2008 by Lippincott Williams & Wilkins.",Epilepsy;Metabolic disorders;Neurometabolic disorders;4 aminobutyric acid metabolism;5 amino 4 imidazolecarboxamide deficiency/dt [Drug Therapy];aciduria;adenylosuccinate lyase deficiency/dt [Drug Therapy];adjuvant therapy;Alpers disease;amniocentesis;aspartylglycosaminuria;ataxia telangiectasia;biotinidase deficiency;blood analysis;bone marrow transplantation;carbohydrate diet;cerebrotendinous xanthomatosis;diet restriction;diet therapy;disorders of amino acid and protein metabolism;disorders of carbohydrate metabolism/dt [Drug Therapy];disorders of peroxisomal functions;enzyme analysis;enzyme deficiency/dt [Drug Therapy];enzyme deficiency/th [Therapy];epilepsy/dr [Drug Resistance];epilepsy/dt [Drug Therapy];epilepsy/et [Etiology];epilepsy/th [Therapy];exchange blood transfusion;gangliosidosis;Gaucher disease;genetic analysis;genetic counseling;genetic disorder;glucose transporter 1 deficiency;human;hyperglycemia;inborn error of metabolism;ketogenic diet;lipofuscinosis;liver transplantation;maple syrup urine disease/th [Therapy];Menkes syndrome/dt [Drug Therapy];metabolic disorder;metachromatic leukodystrophy;neuroaxonal dystrophy;newborn period;nuclear magnetic resonance imaging;peritoneal dialysis;phenylketonuria/th [Therapy];porphyria/dt [Drug Therapy];priority journal;protein restriction;pyruvate carboxylase deficiency/dt [Drug Therapy];pyruvate carboxylase deficiency/su [Surgery];pyruvate dehydrogenase deficiency/th [Therapy];review;Sanfilippo syndrome;sialidosis;ultrasound;Wilson disease/dt [Drug Therapy];4 aminobutyrate aminotransferase;5 hydroxytryptophan/dt [Drug Therapy];adenine/dt [Drug Therapy];allopurinol/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];biotin/dt [Drug Therapy];clonazepam/dt [Drug Therapy];copper/dt [Drug Therapy];dextromethorphan/dt [Drug Therapy];etiracetam/dt [Drug Therapy];folinic acid/dt [Drug Therapy];gabapentin/dt [Drug Therapy];heptanoic acid derivative/dt [Drug Therapy];histidine/dt [Drug Therapy];lamotrigine/dt [Drug Therapy];levodopa/dt [Drug Therapy];magnesium sulfate/dt [Drug Therapy];oxcarbazepine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];pyridoxamine phosphate oxidase;pyridoxine/dt [Drug Therapy];ribose/dt [Drug Therapy];sulfite oxidase;topiramate/dt [Drug Therapy];uridine/dt [Drug Therapy];valproic acid/dt [Drug Therapy],"Pascual, J. M.;Campistol, J.;Gil-Nagel, A.",2008,November,http://dx.doi.org/10.1097/01.nrl.0000340787.30542.41,0,0,
1968,Efficacy of tetrathiomolybdate in a mouse model of multiple sclerosis,"Tetrathiomolybdate (TM) is a potent anticopper drug developed for Wilson's disease. We have found multiple efficacious results from decreasing copper levels with TM in mouse models of disease, using serum Cp as a surrogate marker of copper status and targeting Cp values of 20% to 50% of baseline. We have found efficacious results of TM therapy in mouse models of fibrosis; inflammation; damage from exogenous agents, such as acetaminophen and doxorubicin; and immune-modulated diseases, such as concanavalin A hepatitis, collagen II-induced arthritis, and the non-obese diabetic (NOD) mouse model of type I diabetes. In the current study, we examine TM efficacy in the EAE mouse model of multiple sclerosis (MS). We find that clinical scores of neurologic damage are significantly inhibited by TM therapy, whether therapy is started before MS-inducing antigen administration or after symptoms from antigen administration develop. Furthermore, we find that experimental autoimmune encephalomyelitis (EAE) treatment produces a marked increase of oxidant damage, as measured by urine isoprostane levels, and TM suppresses these isoprostane increases strongly and significantly. Finally, we find marked increases of inflammatory and immune-related cytokines in this model, and we find that TM strongly and significantly suppresses these increases. © 2008.",allergic encephalomyelitis/dt [Drug Therapy];allergic encephalomyelitis/pc [Prevention];animal experiment;animal model;animal tissue;article;controlled study;cytokine production;drug efficacy;experimental model;female;inflammation;mouse;multiple sclerosis/dt [Drug Therapy];multiple sclerosis/pc [Prevention];nervous system injury;nonhuman;priority journal;Swiss James Lambert mouse;urine level;isoprostane/ec [Endogenous Compound];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/ip [Intraperitoneal Drug Administration];tetrathiomolybdic acid/pd [Pharmacology],"Hou, G.;Abrams, G. D.;Dick, R.;Brewer, G. J.",2008,November,http://dx.doi.org/10.1016/j.trsl.2008.09.003,0,0,
1969,Clinical trials of orphan medicines,,acromegaly;adenomatous polyp;adrenal cortex carcinoma;Barrett esophagus;cataplexy;chronic myeloid leukemia;chronic pain;clinical study;clinical trial;dermatofibrosarcoma protuberans;drug approval;drug efficacy;drug marketing;drug safety;drug screening;dysplasia;Fabry disease/rh [Rehabilitation];gastrointestinal stromal tumor;Gaucher disease;glioma;glycogen storage disease type 2;homocystinuria;human;hyperammonemia;incidence;kidney carcinoma;Lennox Gastaut syndrome;Maroteaux Lamy syndrome;mucopolysaccharidosis;narcolepsy;patent ductus arteriosus;postmarketing surveillance;priority journal;promyelocytic leukemia;pulmonary hypertension;rare disease;review;risk benefit analysis;support group;survival rate;systemic sclerosis;thrombocythemia;treatment indication;tyrosinemia;Wilson disease;agalsidase alfa/ct [Clinical Trial];agalsidase beta/ct [Clinical Trial];anagrelide/ct [Clinical Trial];arsenic trioxide/ct [Clinical Trial];bosentan/ct [Clinical Trial];carglumic acid/ct [Clinical Trial];celecoxib/ct [Clinical Trial];clofarabine/ct [Clinical Trial];dasatinib/ct [Clinical Trial];deferasirox/ct [Clinical Trial];galsulfase/ct [Clinical Trial];ibuprofen/ct [Clinical Trial];iloprost/ct [Clinical Trial];imatinib/ct [Clinical Trial];laronidase/ct [Clinical Trial];miglustat/ct [Clinical Trial];mitotane/ct [Clinical Trial];nitisinone/ct [Clinical Trial];omega conotoxin MVIIA/ct [Clinical Trial];orphan drug/ct [Clinical Trial];orphan drug/pe [Pharmacoeconomics];oxybate sodium/ct [Clinical Trial];pegvisomant/ct [Clinical Trial];photofrin/ct [Clinical Trial];razoxane/ct [Clinical Trial];sildenafil/ct [Clinical Trial];sitaxsentan/ct [Clinical Trial];stiripentol/ct [Clinical Trial];sunitinib/ct [Clinical Trial];unindexed drug;zinc acetate/ct [Clinical Trial],"Buckley, B. M.",2008,,http://dx.doi.org/10.1016/S0140-6736%2808%2960876-4,0,0,
1970,Genetics and public health in post-genomic era,"Although clinical genetics had its roots predating Mendel's discovery, the clinical case histories were not documented in terms of genes or loci. Even when such defects were shown to follow Mendelian rules of transmission, this was not sufficient to manage the problem. It was only when cytogenetic and more precisely biochemical or molecular basis of disorders was known, the field established its status all over the world. In post genomic era, the scope has widened and genetic service has become almost a necessity for public health. © 2008 Academic Journals Inc.",Biochemical;Ethics;Gene therapy;Genetic counseling;Genetic disorders;Molecular markers;amniocentesis;aneuploidy;article;autosomal dominant disorder/cn [Congenital Disorder];autosomal recessive disorder/cn [Congenital Disorder];chromosome aberration;chromosome breakage;chromosome deletion;chromosome disorder/cn [Congenital Disorder];chromosome duplication;chromosome inversion;chromosome translocation;chronic disease;clinical genetics;congenital adrenal hyperplasia/cn [Congenital Disorder];congenital adrenal hyperplasia/dt [Drug Therapy];congenital hypothyroidism/cn [Congenital Disorder];congenital hypothyroidism/dt [Drug Therapy];congenital malformation/cn [Congenital Disorder];demethylation;diabetes mellitus/cn [Congenital Disorder];diabetes mellitus/dt [Drug Therapy];diet therapy;ecological genetics;enzyme replacement;fragile X syndrome/cn [Congenital Disorder];galactosemia/cn [Congenital Disorder];galactosemia/th [Therapy];gene isolation;genetic database;genetic disorder/cn [Congenital Disorder];genetic disorder/di [Diagnosis];genetic disorder/dt [Drug Therapy];genetic disorder/pc [Prevention];genetic disorder/th [Therapy];genetic risk;genetic screening;genetic susceptibility;genomics;hemophilia/cn [Congenital Disorder];hemophilia/dt [Drug Therapy];human;human genome;inborn error of metabolism/cn [Congenital Disorder];incidence;isochromosome;karyotype;Lesch Nyhan syndrome/cn [Congenital Disorder];Lesch Nyhan syndrome/dt [Drug Therapy];medical ethics;medical genetics;mixoploidy;molecular genetics;monogenic disorder/cn [Congenital Disorder];pharmacogenetics;phenylketonuria/cn [Congenital Disorder];phenylketonuria/th [Therapy];pituitary dwarfism/cn [Congenital Disorder];pituitary dwarfism/dt [Drug Therapy];prenatal diagnosis;public health;ring chromosome;tissue transplantation;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];X chromosome linked disorder/cn [Congenital Disorder];Y chromosome linked disorder/cn [Congenital Disorder];allopurinol/dt [Drug Therapy];blood clotting factor 8/dt [Drug Therapy];growth hormone/dt [Drug Therapy];insulin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];steroid/dt [Drug Therapy];thyroxine/dt [Drug Therapy],"Afzal, M.;Siddique, Y. H.;Beg, T.;Ara, G.;Gupta, J.",2008,,http://dx.doi.org/10.3923/tmr.2008.41.63,0,0,
1971,Zinc therapy of Wilson's disease: A case report. [Chinese],,adolescent;article;case report;computer assisted tomography;female;hemoglobin determination;human;leukocyte count;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];creatine kinase/ec [Endogenous Compound];creatine kinase MB/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Xu, Y.;Tang, S. Q.",2008,May,http://dx.doi.org/10.3724/SP.J.1008.2008.00579,0,0,
1972,Orphan drug use in pediatrics. [Spanish],"Introduction: Analysis of orphan drugs' use by pediatric outpatients. Methods: Retrospective observational study of pediatric patients under treatment with orphan drugs from January 2006 to March 2007. The following variables were collected: age, gender, prescription and drug type. Results: Medication was dispensed for 197 outpatients. 19 patients received some treatment with orphan drugs, whose average age was 7.29 years. There were seven prescribing departments. Orphan drug consumption by pediatric outpatients during the studied period was 5.90% of all drugs. It produced 17.27% of the total expenditures of the dispensed drugs to these patients. Discussion: The Hospital Formulary should also include orphan drugs, with the purpose of efficiently and timely resolving the treatment of rare diseases.",Orphan drugs;Pediatric outpatients;Pharmaceutical dispensation;Prescription;adrenal cortex carcinoma/dt [Drug Therapy];age distribution;ambulatory care;article;disorders of amino acid and protein metabolism/dt [Drug Therapy];drug formulary;drug use;drug utilization;gender;hospital pharmacy;human;kidney failure/dt [Drug Therapy];lymphatic leukemia/dt [Drug Therapy];Menkes syndrome/dt [Drug Therapy];observational study;outpatient care;pediatrics;phenylketonuria/dt [Drug Therapy];prematurity/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];retrospective study;sex ratio;treatment indication;tyrosinemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];arylbutyric acid derivative/dt [Drug Therapy];arylbutyric acid derivative/pr [Pharmaceutics];bosentan/dt [Drug Therapy];bosentan/pr [Pharmaceutics];ibuprofen/dt [Drug Therapy];ibuprofen/iv [Intravenous Drug Administration];ibuprofen/pr [Pharmaceutics];iloprost/dt [Drug Therapy];iloprost/pr [Pharmaceutics];imatinib/dt [Drug Therapy];imatinib/pr [Pharmaceutics];mitotane/dt [Drug Therapy];mitotane/pr [Pharmaceutics];nitisinone/dt [Drug Therapy];nitisinone/pr [Pharmaceutics];orphan drug/dt [Drug Therapy];orphan drug/pr [Pharmaceutics];sildenafil/dt [Drug Therapy];sildenafil/pr [Pharmaceutics];tetrahydrobiopterin/dt [Drug Therapy];tetrahydrobiopterin/pr [Pharmaceutics];trientine/dt [Drug Therapy];trientine/pr [Pharmaceutics];trometamol/dt [Drug Therapy];trometamol/pr [Pharmaceutics];zinc acetate/dt [Drug Therapy];zinc acetate/pr [Pharmaceutics],"Amor Ruiz, I. Ma;Gallego Fernandez, C.;Delgado Rey Ma, S.",2008,July/August,,0,0,
1973,Medical countermeasures against nuclear threats: Radionuclide decorporation agents,"Exposure to radionuclides disseminated by a radiological dispersion device or deposited as fallout after a nuclear power plant accident or detonation of an improvised nuclear device could result in internal contamination of a significant number of individuals. Internalized radionuclides may cause both acute and chronic radiation injury and increase an individual's risk of developing cancer. This damage and risk can be mitigated by the use of decorporation agents that reduce internal contamination. Unfortunately, most effective agents decorporate only a limited range of radionuclides, and some are formulated in ways that would make administration in mass casualty situations challenging. There is a need for new radionuclide decorporation agents, reformulations of existing agents, and/or expansion of the labeled indications for existing treatments. Researchers developing novel or improved decorporation agents should also understand the regulatory pathway for these products. This workshop, the first in nearly half a century to focus exclusively on radionuclide decorporation, brought together researchers and scientific administrators from academia, government and industry as well as senior regulatory affairs officers and U.S. Food and Drug Administration personnel. Meeting participants reviewed recent progress in the development of decorporation agents and contemplated the future of the field. © 2008 by Radiation Research Society.",atomic bomb;cancer risk;conference paper;cystinuria/dt [Drug Therapy];drug bioavailability;fallout;food and drug administration;good laboratory practice;good manufacturing practice;health care;health care policy;health program;human;intoxication/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];mercurialism/dt [Drug Therapy];nonhuman;nuclear accident;priority journal;radiation injury/dt [Drug Therapy];radiation sickness/dt [Drug Therapy];rheumatoid arthritis/dt [Drug Therapy];risk factor;Wilson disease/dt [Drug Therapy];actinide;antidote/dt [Drug Therapy];antidote/po [Oral Drug Administration];calcium diethylenetriaminepentaacetic acid/dt [Drug Therapy];calcium diethylenetriaminepentaacetic acid/ih [Inhalational Drug Administration];calcium diethylenetriaminepentaacetic acid/iv [Intravenous Drug Administration];calcium diethylenetriaminepentaacetic acid/po [Oral Drug Administration];calcium diethylenetriaminepentaacetic acid/pr [Pharmaceutics];cesium;chelating agent/dt [Drug Therapy];chelating agent/po [Oral Drug Administration];chitosan/dt [Drug Therapy];chitosan/po [Oral Drug Administration];cobalt;deferriferrithiocin/cm [Drug Comparison];deferriferrithiocin/po [Oral Drug Administration];deferriferrithiocin derivative;dimercaprol/dt [Drug Therapy];dimercaprol/po [Oral Drug Administration];ferric ferrocyanide/dt [Drug Therapy];ferric ferrocyanide/po [Oral Drug Administration];iodine;iron chelating agent;lanthanide;metal;nanoparticle;penicillamine/dt [Drug Therapy];penicillamine/iv [Intravenous Drug Administration];penicillamine/po [Oral Drug Administration];pentetic acid/cm [Drug Comparison];pentetic acid/cr [Drug Concentration];pentetic acid/dt [Drug Therapy];pentetic acid/iv [Intravenous Drug Administration];pentetic acid/po [Oral Drug Administration];pentetic acid/pr [Pharmaceutics];pentetic acid/pk [Pharmacokinetics];pentetic acid/sc [Subcutaneous Drug Administration];pentetic acid derivative/dt [Drug Therapy];pentetic acid derivative/ih [Inhalational Drug Administration];pentetic acid derivative/iv [Intravenous Drug Administration];pentetic acid derivative/po [Oral Drug Administration];pentetic acid derivative/pr [Pharmaceutics];plutonium;pyridine derivative/dv [Drug Development];pyridine derivative/dt [Drug Therapy];pyridine derivative/po [Oral Drug Administration];radioisotope;siderophore/dt [Drug Therapy];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];thorium;trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];triethylenetetraminehexaacetic acid derivative/cm [Drug Comparison];triethylenetetraminehexaacetic acid derivative/dt [Drug Therapy];triethylenetetraminehexaacetic acid derivative/pr [Pharmaceutics];unclassified drug;unithiol/dt [Drug Therapy];unithiol/po [Oral Drug Administration];uranium;zinc diethylenetriaminepentaacetic acid/dt [Drug Therapy];zinc diethylenetriaminepentaacetic acid/ih [Inhalational Drug Administration];zinc diethylenetriaminepentaacetic acid/iv [Intravenous Drug Administration];zinc diethylenetriaminepentaacetic acid/po [Oral Drug Administration];zinc diethylenetriaminepentaacetic acid/pr [Pharmaceutics],"Cassatt, D. R.;Kaminski, J. M.;Hatchett, R. J.;DiCarlo, A. L.;Benjamin, J. M.;Maidment, B. W.",2008,October,http://dx.doi.org/10.1667/RR1485.1,0,0,
1974,Delusional disorder and alcohol abuse in a patient with Wilson's disease,"Objective: Wilson's disease (WD) or hepatolenticular degeneration is a rare disorder of copper metabolism that results in copper deposition in brain, liver, kidneys and the cornea. Due to the copper deposits in the brain, neurological and psychiatric symptoms may appear. The psychiatric manifestations may vary from mood disorders, behavioral and personality disorders to cognitive impairment, while psychotic symptoms are rarely reported. The objective of this report was to present an unusual case of WD presenting with nonpersecutory delusional disorder and alcohol abuse in the absence of neurological signs. Case Summary: A 34-year-old male patient, without any previous psychiatric or alcohol abuse history, presented with delusions of jealousy and alcohol abuse when he discontinued his treatment for WD. Although the patient had no previous symptoms or neurological signs, he was receiving treatment for WD for 3 years, after being diagnosed with the disease during family precautionary examination, since his brother developed symptomatic WD. The patient started combined pharmacotherapy, and after 3 months of follow-up the psychiatric manifestations were controlled sufficiently. Conclusions: Although WD is rarely associated with alcohol abuse and delusions of jealousy, this disease should be taken into account in the differential diagnosis of these psychiatric manifestations. © 2008 Elsevier Inc. All rights reserved.",Alcohol;Delusions;Psychiatric;Psychotic;Wilson's disease;adult;alcohol abuse;anamnesis;article;case report;clinical feature;delusional disorder/dt [Drug Therapy];Diagnostic and Statistical Manual of Mental Disorders;drug substitution;drug withdrawal;family history;fever/si [Side Effect];human;human tissue;laboratory test;liver biopsy;male;neurologic examination;nuclear magnetic resonance imaging;Wilson disease/dt [Drug Therapy];chlordiazepoxide/cb [Drug Combination];chlordiazepoxide/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];risperidone/cb [Drug Combination];risperidone/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy],"Spyridi, S.;Diakogiannis, I.;Michaelides, M.;Sokolaki, S.;Iacovides, A.;Kaprinis, G.",2008,November 2008/December,http://dx.doi.org/10.1016/j.genhosppsych.2008.05.005,0,0,
1975,"The pharmacist, rare diseases and orphan medicines. [Spanish]","Treatment of rare diseases is often complicated due to the difficulties posed by the research and development of medicines by the pharmacological industry. One of the greatest concerns of this group of patients, which is both scarce and diverse, is access to available medicines. The European Medicine Agency establishes the term orphan medicines and the incentives and bases for their commercialisation. Due to their special characteristics, the majority of orphan medicines require suitable vigilance and control. The hospital pharmacy services are actively involved in their management and supply, as well as in a correct pharmacotherapeutic monitoring of the patients.",Management;Orphan medicines;Pharmaceutical care;Rare diseases;adrenal suppression;alanine aminotransferase blood level;alkaline phosphatase blood level;alopecia/si [Side Effect];aminotransferase blood level;amylase blood level;anemia/si [Side Effect];anorexia/si [Side Effect];anxiety;arthralgia/si [Side Effect];asthenia/si [Side Effect];bleeding/si [Side Effect];blurred vision/si [Side Effect];bone marrow suppression/si [Side Effect];bronchitis/si [Side Effect];cellulitis/si [Side Effect];chronic myeloid leukemia/dt [Drug Therapy];clinical trial;confusion/si [Side Effect];constipation/si [Side Effect];coughing/si [Side Effect];creatinine blood level;depression/si [Side Effect];dermatitis/si [Side Effect];diarrhea/si [Side Effect];digestive system function disorder/si [Side Effect];disorders of mitochondrial functions/dt [Drug Therapy];dreaming;drug control;drug dose reduction;drug effect;drug eruption/si [Side Effect];drug hypersensitivity/si [Side Effect];drug industry;drug marketing;drug monitoring;drug research;dyspepsia/si [Side Effect];dyspnea/si [Side Effect];edema/si [Side Effect];eosinophilic leukemia/dt [Drug Therapy];epigastric pain/si [Side Effect];erythema/si [Side Effect];evening dosage;excitement;eye disease/si [Side Effect];Fabry disease/dt [Drug Therapy];fatigue/si [Side Effect];fever/si [Side Effect];fluid retention;gastrointestinal disease/si [Side Effect];gastrointestinal irritation/si [Side Effect];gastrointestinal stromal tumor/dt [Drug Therapy];hair loss/si [Side Effect];hand foot syndrome/si [Side Effect];health care access;health care delivery;health care management;heart disease/si [Side Effect];heart infarction/si [Side Effect];heart muscle ischemia/si [Side Effect];heart palpitation/si [Side Effect];hospital pharmacy;hospital service;human;hypereosinophilia/dt [Drug Therapy];hyperglycemia/si [Side Effect];hyperkinesia/si [Side Effect];hyperpigmentation/si [Side Effect];hypertension/dt [Drug Therapy];hypertension/si [Side Effect];hypoglycemia/si [Side Effect];induced hypotension;infertility/si [Side Effect];influenza/si [Side Effect];insomnia/si [Side Effect];irritability;kidney carcinoma/dt [Drug Therapy];kidney failure/si [Side Effect];leukocytosis/si [Side Effect];leukopenia/si [Side Effect];liver cell carcinoma/dt [Drug Therapy];liver failure/si [Side Effect];liver function;liver toxicity/si [Side Effect];lung dysplasia/si [Side Effect];lung embolism/dt [Drug Therapy];lung embolism/si [Side Effect];migraine/si [Side Effect];multiple cycle treatment;multiple myeloma/dt [Drug Therapy];muscle cramp/si [Side Effect];musculoskeletal pain/si [Side Effect];myelodysplasia/dt [Drug Therapy];myeloproliferative disorder/dt [Drug Therapy];narcolepsy/dt [Drug Therapy];nausea/si [Side Effect];nausea and vomiting/si [Side Effect];necrotizing enterocolitis/si [Side Effect];neuropathy/si [Side Effect];neutropenia/si [Side Effect];night sweat/si [Side Effect];nose congestion/si [Side Effect];organization;paresthesia/si [Side Effect];patient monitoring;peripheral neuropathy/si [Side Effect];pharmacist;polyuria/si [Side Effect];promyelocytic leukemia/dt [Drug Therapy];pruritus/si [Side Effect];pulmonary hypertension/dt [Drug Therapy];QT prolongation/si [Side Effect];rare disease/dt [Drug Therapy];rash/si [Side Effect];repeated drug dose;review;rhinopharyngitis/si [Side Effect];side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];sinusitis/si [Side Effect];skin disease/si [Side Effect];skin redness/si [Side Effect];sodium blood level;stomach irritation/si [Side Effect];systemic sclerosis/dt [Drug Therapy];tachycardia/si [Side Effect];thalassemia major/dt [Drug Therapy];thrombocytopenia/si [Side Effect];tremor/si [Side Effect];triacylglycerol lipase blood level;tyrosinemia/dt [Drug Therapy];urticaria/si [Side Effect];venous thromboembolism/si [Side Effect];vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];agalsidase beta/ae [Adverse Drug Reaction];agalsidase beta/dt [Drug Therapy];agalsidase beta/iv [Intravenous Drug Administration];arsenic trioxide/ae [Adverse Drug Reaction];arsenic trioxide/dt [Drug Therapy];arsenic trioxide/iv [Intravenous Drug Administration];bosentan/ae [Adverse Drug Reaction];bosentan/dt [Drug Therapy];bulsivex;busulfan/ae [Adverse Drug Reaction];busulfan/dt [Drug Therapy];carglumic acid/ae [Adverse Drug Reaction];carglumic acid/dt [Drug Therapy];clofarabine/ae [Adverse Drug Reaction];clofarabine/dt [Drug Therapy];clofarabine/iv [Intravenous Drug Administration];dasatinib/ae [Adverse Drug Reaction];dasatinib/dt [Drug Therapy];deferasirox/ae [Adverse Drug Reaction];deferasirox/dt [Drug Therapy];dexamethasone/cb [Drug Combination];dexamethasone/dt [Drug Therapy];ibuprofen/ae [Adverse Drug Reaction];ibuprofen/dt [Drug Therapy];idebenone/ae [Adverse Drug Reaction];idebenone/dt [Drug Therapy];imatinib/ae [Adverse Drug Reaction];imatinib/dt [Drug Therapy];lenalidomide/ae [Adverse Drug Reaction];lenalidomide/cb [Drug Combination];lenalidomide/dt [Drug Therapy];nitisinone/ae [Adverse Drug Reaction];nitisinone/dt [Drug Therapy];orphan drug/ct [Clinical Trial];orphan drug/dv [Drug Development];orphan drug/dt [Drug Therapy];oxybate sodium/ae [Adverse Drug Reaction];oxybate sodium/dt [Drug Therapy];sildenafil/ae [Adverse Drug Reaction];sildenafil/dt [Drug Therapy];sorafenib/ae [Adverse Drug Reaction];sorafenib/dt [Drug Therapy];sunitinib/ae [Adverse Drug Reaction];sunitinib/dt [Drug Therapy];ubidecarenone/ae [Adverse Drug Reaction];ubidecarenone/dt [Drug Therapy];unclassified drug;wilzin;zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy],"Nagore Indurain, C.;Lacalle, E.;Arteche, L.",2008,,,0,0,
1976,Acute liver failure: Development course. [Spanish],,article;autoimmune hepatitis/dt [Drug Therapy];brain edema;cause of death;clinical evaluation;clinical feature;disease association;disease classification;disease course;hepatic encephalopathy;hepatitis B/dt [Drug Therapy];human;jaundice;liver failure/ep [Epidemiology];liver regeneration;liver toxicity/dt [Drug Therapy];liver transplantation;mortality;mycosis/dt [Drug Therapy];risk factor;survival rate;treatment contraindication;Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];aciclovir;corticosteroid/dt [Drug Therapy];lamivudine/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy];penicillin G/dt [Drug Therapy];prothrombin/ec [Endogenous Compound],"Alvarez, J. L. M.;Peck, G. S.",2008,June,http://dx.doi.org/10.1016/S1578-1550%2808%2972998-X,0,0,
1977,Pediatric intensive care: Acute liver failure. [Spanish],,article;autoimmune hepatitis/dt [Drug Therapy];blood clotting disorder/dt [Drug Therapy];blood clotting disorder/et [Etiology];brain edema/dt [Drug Therapy];clinical feature;computer assisted tomography;continuous infusion;Doppler flowmetry;galactosemia;hemochromatosis/dt [Drug Therapy];hepatic encephalopathy/co [Complication];hepatitis;human;jaundice;Kupffer cell;liver failure/di [Diagnosis];liver failure/et [Etiology];liver failure/su [Surgery];liver necrosis;liver transplantation;mushroom poisoning;orthotopic transplantation;oxygenation;prognosis;prothrombin time;thorax radiography;treatment indication;tyrosinemia;Wilson disease/dt [Drug Therapy];acetylcysteine;azathioprine/dt [Drug Therapy];blood clotting factor 7/ec [Endogenous Compound];deferoxamine/dt [Drug Therapy];mannitol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];prothrombin/ec [Endogenous Compound];vitamin K group/dt [Drug Therapy],"Delgado, M. A.;Alvarado, F.",2008,August,http://dx.doi.org/10.1016/S1696-2818%2808%2975634-8,0,0,
1978,Zinc supplementation for the treatment or prevention of disease: Current status and future perspectives,"Zinc is a nutritionally essential trace element, and thus zinc deficiency may severely affect human health. Many studies were published in which the effect of nutritional zinc supplementation on the incidence or severity of a certain disease was investigated. This review summarizes the main observations and aims to evaluate the use of nutritional zinc supplementation for prevention and treatment of human disease. © 2007 Elsevier Inc. All rights reserved.",Essential trace element;Immune system;Infection;Zinc;Zinc deficiency;Zinc supplementation;acne vulgaris;acquired immune deficiency syndrome/dt [Drug Therapy];acrodermatitis enteropathica;antibody production;aphthous stomatitis/dt [Drug Therapy];atopic dermatitis;common cold/dt [Drug Therapy];diabetic neuropathy;diarrhea/dt [Drug Therapy];disease association;Down syndrome;drug effect;health hazard;helper cell;human;Human immunodeficiency virus infection/dt [Drug Therapy];immune response;in vitro study;insulin dependent diabetes mellitus;leg ulcer;leprosy/dt [Drug Therapy];lower respiratory tract infection/dt [Drug Therapy];malaria/dt [Drug Therapy];mouth ulcer;neoplasm/co [Complication];non insulin dependent diabetes mellitus;priority journal;psoriasis;psoriasis vulgaris;psoriatic arthritis;rheumatoid arthritis;rosacea;short survey;sickle cell anemia;signal transduction;skin leishmaniasis/dt [Drug Therapy];treatment outcome;trisomy 21;tuberculosis/dt [Drug Therapy];vaccination;verruca vulgaris;vitamin supplementation;Wilson disease;yellow nail syndrome;zinc deficiency/dt [Drug Therapy];clofazimine/dt [Drug Therapy];dapsone/dt [Drug Therapy];thymulin/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Haase, H.;Overbeck, S.;Rink, L.",2008,May,http://dx.doi.org/10.1016/j.exger.2007.12.002,0,0,
1979,Rheumatology 50 years ago: A short personal history,"This report reviews attitudes to the rheumatic diseases and treatment methods in use some 50 years ago. The focus is on Professor J. H. Kellgren's unit at the Manchester Royal Infirmary in the UK. For rheumatoid arthritis, aspirin, phenylbutazone, gold injections, antimalarials and prednisolone were all available and bed rest was probably overused. The Charnley hip replacement arthroplasty was being trialed but in 1960 had not been perfected. Kellgren and the two other great UK figures in rheumatology at the time, E. G. L. Bywaters and J. J. R. Duthie appeared to me to have only a limited interest in immunology, apart from the role of rheumatoid factor in rheumatoid arthritis and related conditions. Concentration remained to some extent on proteoglycans and collagen as befitting the 1950s concept of 'collagen diseases'. © 2008 Asia Pacific League of Associations for Rheumatology.",Ankylosing spondylitis;Aspirin;Disease modifying agents;Rheumatoid arthritis;ankylosing spondylitis/dt [Drug Therapy];arthrodesis;attitude to health;clinical protocol;clinical trial;drug dose reduction;erythrocyte sedimentation rate;gout;hip arthroplasty;human;knee osteoarthritis;medical education;metatarsophalangeal joint;note;pathophysiology;priority journal;rheumatic disease/et [Etiology];rheumatoid arthritis/dt [Drug Therapy];rheumatoid arthritis/et [Etiology];rheumatology;subluxation/su [Surgery];unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];acetylsalicylic acid/dt [Drug Therapy];antimalarial agent/dt [Drug Therapy];antirheumatic agent/dt [Drug Therapy];azathioprine/dt [Drug Therapy];collagen/ec [Endogenous Compound];corticosteroid/ad [Drug Administration];corticosteroid/dt [Drug Therapy];corticosteroid/ar [Intraarticular Drug Administration];corticosteroid/po [Oral Drug Administration];cyclophosphamide/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];disease modifying antirheumatic drug/dt [Drug Therapy];indometacin/dt [Drug Therapy];leflunomide/dt [Drug Therapy];methotrexate/dt [Drug Therapy];methotrexate/po [Oral Drug Administration];nonsteroid antiinflammatory agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenylbutazone/dt [Drug Therapy];prednisolone/ae [Adverse Drug Reaction];prednisolone/ct [Clinical Trial];prednisolone/do [Drug Dose];prednisolone/dt [Drug Therapy];proteoglycan/ec [Endogenous Compound];rheumatoid factor/ec [Endogenous Compound];salazosulfapyridine/dt [Drug Therapy],"Muirden, K. D.",2008,September,http://dx.doi.org/10.1111/j.1756-185X.2008.00361.x,0,0,
1980,Atypical presentation of Wilson's disease,"Wilson's disease, an inborn error of copper metabolism, is a relatively rare familial disorder inherited as an autosomal recessive trait but treatable condition that often presents diagnostic dilemmas. We report below a case with some uncommon but well documented features of the disease with review of literature.",Hyperpigmentation;KF ring;Vitamin A deficiency;Wilson's disease (WD);abdominal distension;article;case report;ceruloplasmin blood level;clinical feature;fever;human;jaundice;laboratory test;male;night blindness/dt [Drug Therapy];ophthalmoscopy;physical examination;retinol deficiency;school child;urine level;visual impairment;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];retinol/dt [Drug Therapy],"Gurubacharya, S. M.;Gurubacharya, R. L.",2008,July/December,,0,0,
1981,A single-center experience with liver transplantation for Wilson's disease,"Wilson's disease is an inherited disorder of copper metabolism, presenting with prominent hepatic and neurologic manifestations. There is an established place for liver transplantation in the presence of liver disease, while the indication for neurologic manifestations is debated. Between 1993 and 2005, 11 patients were liver transplanted for Wilson's disease at our institution. We retrospectively reviewed the medical records of the patients. The pathology of the explanted livers was analyzed. The patients were divided into three groups based on the evolution of the disease. Postoperative data gathered included patient and graft outcome, complications, neurologic status, and copper metabolism. Six males and five females were transplanted at a mean age of 29.7yr (range 15-48yr). Three patients had a fulminant presentation, two patients had decompensation of established disease, and six patients had chronic disease. Neurologic features were prominent in five patients. The pathologic analysis of the explanted graft showed cirrhosis in all patients. The five patients with fulminant and acute on chronic presentations also showed necrosis in the explant. The mean postoperative follow-up was 56.8 months (range 10-129 months). Two patients were re-transplanted. One patient died because of severe sepsis. Two patients with severe neurologic dysfunction showed significant remission of symptoms. Liver transplantation is a safe and effective treatment for both acute and chronic presentations of Wilson's disease. Acute presentation correlates with the presence of necrosis in the explanted liver. In our series, there was a relevant improvement of the neurologic features after transplantation. © Journal compilation © 2008 Blackwell Munksgaard.",adolescent;adult;article;chronic liver disease/su [Surgery];clinical article;clinical effectiveness;clinical feature;copper metabolism;correlation analysis;disease activity;female;follow up;graft survival;human;liver cirrhosis/su [Surgery];liver failure/su [Surgery];liver necrosis;liver transplantation;male;medical record review;mortality;neurologic disease;priority journal;remission;reoperation;retrospective study;sepsis;treatment outcome;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Martin, A. P.;Bartels, M.;Redlich, J.;Hauss, J.;Fangmann, J.",2008,March/April,http://dx.doi.org/10.1111/j.1399-0012.2007.00777.x,0,0,
1982,P wave dispersion is prolonged in patients with Wilson's disease,"Aim: To investigate the P wave dispersion as a noninvasive marker of intra-atrial conduction disturbances in patients with Wilson's disease. Methods: We compared Wilson's disease patients (n = 18) with age matched healthy subjects (n = 15) as controls. The diagnosis was based on clinical symptoms, laboratory tests (ceruloplasmin, urinary and hepatic copper concentrations). P wave dispersion, a measurement of the heterogeneity of atrial depolarization, was measured as the difference between the duration of the longest and the shortest P-waves in 12 lead electrocardiography. Results: All the patients were asymptomatic on cardiological examination and have sinusal rhythm in electrocardiography. Left ventricular and left atrial diameters, left ventricular ejection fraction and left ventricular mass index were similar in both groups. The Wilson's disease patients had a significantly higher P wave dispersion compared with the controls (44.7 +/- 5.8 vs 25.7 +/- 2.5, P < 0.01). Conclusion: There was an increase in P wave dispersion in cardiologically asymptomatic Wilson's disease patients which probably represents an early stage of cardiac involvement. © 2008 WJG. All rights reserved.",Atrial depolarization;Electrocardiography;P wave dispersion;P wave duration;Wilson's disease;adolescent;adult;article;chelation therapy;clinical article;clinical feature;controlled study;disease marker;drug substitution;drug withdrawal;heart depolarization;heart left atrium;heart left ventricle ejection fraction;heart left ventricle mass;heart left ventricle size;heart muscle conduction disturbance/di [Diagnosis];human;laboratory test;liver level;P wave;protein urine level;school child;sinus rhythm;symptom;thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration],"Arat, N.;Kacar, S.;Golbasi, Z.;Akdogan, M.;Sokmen, Y.;Kuran, S.;Idilman, R.",2008,28 Feb,http://dx.doi.org/10.3748/wjg.14.1252,0,0,
1983,"Chelators controlling metal metabolism and toxicity pathways: Applications in cancer prevention, diagnosis and treatment","Chelating drugs and chelator metal complexes are used for the prevention, diagnosis and treatment of cancer. Cancer cells and normal cells require essential metal ions such as iron, copper and zinc for growth and proliferation. Chelators can target the metabolic pathways of cancer cells through the control of proteins involved in the regulation of these metals and also of other molecules involved in cell cycle control, angiogenesis and metastatic suppression. Other targets include the inhibition of specific proteins such as ribonucleotide reductase involved in DNA synthesis, the inhibition of free radical damage on DNA caused by iron and copper catalytic centers, the inhibition of microbial growth in immuno compromised cancer patients and the decorporation of radioactive and other toxic metals causing cancer. Chelating drugs and metal ions can affect the metabolism, efficacy and toxicity of anti-cancer drugs such as doxorubicin, mitozantrone, bleiomycin and hydroxyurea (HU). Although many experimental chelators have been shown to be effective as anti-cancer agents, only a few, e.g., dexrazoxane, deferoxamine (DFO) and triapine, have reached the stage of clinical testing or application. In many experimental models, deferiprone (L1) has been shown to be effective in cancer prevention and treatment, and in the inhibition of doxorubicin-induced cardiotoxicity. New anti-cancer drugs could be developed using chelators and chelator complexes with platinum and other metals, and also new protocols of combinations of chelators with known anti-cancer drugs. Copyright © Informa Healthcare USA, Inc.",Anti-cancer drugs;Antioxidants;Cancer;Chelators;Deferiprone (L1);Deferoxamine (DFO);Free radicals;Iron;Metal ions;Targeting;antineoplastic activity;cancer cell;cancer diagnosis;cancer growth;cancer patient;cancer prevention;cancer therapy;cardiotoxicity/dt [Drug Therapy];catalysis;cell cycle regulation;cell proliferation;chemical carcinogenesis;conference paper;DNA damage;DNA synthesis;enzyme inhibition;experimental model;human;immune deficiency;iron deficiency anemia/dt [Drug Therapy];iron overload/dt [Drug Therapy];metal metabolism;metastasis inhibition;microbial growth;myelodysplasia;neoplasm/dt [Drug Therapy];nonhuman;nuclear magnetic resonance imaging;protein function;regulatory mechanism;sickle cell anemia;thalassemia;treatment outcome;tumor vascularization;Wilson disease/dt [Drug Therapy];3 aminopicolinaldehyde thiosemicarbazone/dt [Drug Therapy];antineoplastic agent/cb [Drug Combination];antineoplastic agent/cm [Drug Comparison];antineoplastic agent/dt [Drug Therapy];arsenic acid/to [Drug Toxicity];bleomycin/dt [Drug Therapy];cadmium/to [Drug Toxicity];chelating agent/cb [Drug Combination];chelating agent/cm [Drug Comparison];chelating agent/dv [Drug Development];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];copper/to [Drug Toxicity];deferasirox/dt [Drug Therapy];deferasirox/pd [Pharmacology];deferiprone/dt [Drug Therapy];deferiprone/pd [Pharmacology];deferoxamine/dt [Drug Therapy];deferoxamine/pd [Pharmacology];doxorubicin/dt [Drug Therapy];doxorubicin/to [Drug Toxicity];ferrous fumarate/dt [Drug Therapy];ferrous gluconate/dt [Drug Therapy];free radical/to [Drug Toxicity];hydroxyurea/dt [Drug Therapy];iron/to [Drug Toxicity];metal/to [Drug Toxicity];metal complex/to [Drug Toxicity];mitoxantrone/dt [Drug Therapy];nickel/to [Drug Toxicity];nuclear magnetic resonance imaging agent;penicillamine/dt [Drug Therapy];plutonium/to [Drug Toxicity];protein/ec [Endogenous Compound];radioactive material;razoxane/dt [Drug Therapy];ribonucleotide reductase/ec [Endogenous Compound];unindexed drug;uranium/to [Drug Toxicity];zinc/to [Drug Toxicity],"Kontoghiorghes, G. J.;Efstathiou, A.;Ioannou-Loucaides, S.;Kolnagou, A.",2008,January,http://dx.doi.org/10.1080/03630260701727119,0,0,
1984,Tetrathiomolybdate versus trientine in the initial treatment of neurologic Wilson's disease,"Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeks* Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05). One patient on trientine had an adverse event while 7 on TM had adverse events. All adverse events were mild. Four patients in the trientine arm died during follow-up, 3 having shown initial neurologic deterioration, 2 patients in the TM arm died. In those patients who did not deteriorate or die, neurologic and speech recovery over 3 years was good. Interpretation: TM is a superior choice to trientine for the initial therapy of neurologic Wilson's disease. © 2008 Cambridge University Press.",Copper toxicity;Double blind trial;Neurologic damage;Tetrathiomolybdate;Trientine;Wilson's disease;alanine aminotransferase blood level;anemia/si [Side Effect];article;aspartate aminotransferase blood level;clinical article;clinical trial;controlled clinical trial;controlled study;copper blood level;disease exacerbation;double blind procedure;drug choice;drug safety;drug tolerability;fatality;follow up;hospital patient;human;laboratory test;leukopenia/si [Side Effect];maintenance therapy;neurologic examination;priority journal;quantitative analysis;randomized controlled trial;scoring system;side effect/si [Side Effect];speech and language assessment;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Brewer, G. J.;Askari, F.;Lorincz, M. T.;Carlson, M.;Schilsky, M.;Kluin, K. J.;Hedera, P.;Moretti, P.;Fink, J. K.;Tankanow, R.;Dick, R. B.;Sitterly, J.",2008,March,http://dx.doi.org/10.1017/S1748232107000043,1,1,
1985,"The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: Therapeutic effects by chelators","Zinc (Zn), copper (Cu) and iron (Fe) are essential minerals that are required for a variety of biomolecules to maintain the normal structure, function, and proliferation of cells. These metals can be toxic in excessive amounts, especially in certain genetic disorders. The homeostasis of these trace elements results from a tightly coordinated regulation by different proteins involved in their uptake, excretion and intracellular storage/trafficking. Through the Fenton reaction, Cu and Fe under a non protein-binding condition, can generate various reactive oxygen species, damaging tissues or cells. Abnormal metabolism of Zn, Cu and Fe can lead to several chronic pathogenesis, such as diabetes or diabetic complications. These pathogenic conditions appear to be prevalent in Zn and Cu deficiency, as well as Cu and Fe overload. In the Fe and Cu overloading conditions, Fe and Cu chelating drugs could be used to control diabetes and diabetic complications. The essentiality, toxicity and roles of these metals in the pathogenesis of diabetes and diabetic complications are discussed. Copyright © Informa Healthcare USA, Inc.",Chelation therapy;Diabetes;Diabetic complications;Insulin resistance;Trace elements;beta thalassemia/dt [Drug Therapy];blood donor;blood transfusion;cardiovascular disease/co [Complication];conference paper;copper deficiency/dt [Drug Therapy];copper metabolism;diabetes control;diabetic nephropathy/co [Complication];diabetogenesis;dietary intake;disease association;drug efficacy;drug safety;Fenton reaction;ferritin blood level;glucose blood level;heart failure/dt [Drug Therapy];hemoglobin blood level;homeostasis;human;insulin dependent diabetes mellitus/dt [Drug Therapy];insulin dependent diabetes mellitus/et [Etiology];insulin dependent diabetes mellitus/pc [Prevention];insulin resistance/co [Complication];insulin resistance/dt [Drug Therapy];insulin resistance/et [Etiology];insulin resistance/pc [Prevention];iron deficiency anemia/dt [Drug Therapy];iron deficiency anemia/th [Therapy];iron metabolism;iron overload/co [Complication];iron therapy;Menkes syndrome/dt [Drug Therapy];non insulin dependent diabetes mellitus/dt [Drug Therapy];non insulin dependent diabetes mellitus/et [Etiology];non insulin dependent diabetes mellitus/pc [Prevention];nonhuman;pancreas disease;pathogenesis;peripheral neuropathy/co [Complication];prevalence;protein binding;protein secretion;protein transport;regulatory mechanism;streptozocin diabetes;thalassemia major/dt [Drug Therapy];thalassemia major/th [Therapy];triacylglycerol blood level;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];zinc deficiency/co [Complication];zinc deficiency/dt [Drug Therapy];zinc deficiency/et [Etiology];zinc metabolism;chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];chelating agent/to [Drug Toxicity];chelating agent/pd [Pharmacology];copper/ec [Endogenous Compound];deferiprone/ae [Adverse Drug Reaction];deferiprone/cb [Drug Combination];deferiprone/dt [Drug Therapy];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/cb [Drug Combination];deferoxamine/dt [Drug Therapy];edetate calcium/pd [Pharmacology];ferritin/ec [Endogenous Compound];glucose/ec [Endogenous Compound];heme/ec [Endogenous Compound];hemoglobin A1c/ec [Endogenous Compound];insulin/dt [Drug Therapy];insulin/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];reactive oxygen metabolite/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];triacylglycerol/ec [Endogenous Compound];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity];zinc/ec [Endogenous Compound];zinc/pd [Pharmacology],"Zheng, Y.;Li, X. K.;Wang, Y.;Cai, L.",2008,January,http://dx.doi.org/10.1080/03630260701727077,0,0,
1986,Herbal medicines in acute viral hepatitis: A ticket for more trouble,"The rapid aggravation of a patient affected by acute liver disease, including the occurrence of acute liver failure, a life-threatening complication, may be due in some cases to recently administered drugs or other xenibiotics. A previously healthy Indian man affected by acute hepatitis E developed acute liver failure after a 5-day treatment by herbal medicines. Pressure on health authorities and education of the general population should help to obviate such avoidable deaths. Physicians have the responsibility to convince their patients affected by acute liver disease not to take medicines for symptomatic relief, especially herbal medicines, up to recovery. The hypothesis is proposed that some of the fatal cases of acute hepatitis E in pregnant women, a common observation in India, could result from an earlier consumption of herbal medicines at the onset of the symptoms of acute hepatitis E. © 2008 Lippincott Williams & Wilkins, Inc.",Acute viral hepatitis deleterious cofactor;Herbal medicines;clinical feature;fatality;health education;hepatitis E/dt [Drug Therapy];human;liver failure/si [Side Effect];liver function;liver toxicity/si [Side Effect];priority journal;risk assessment;short survey;virus hepatitis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];aciclovir/dt [Drug Therapy];aciclovir/iv [Intravenous Drug Administration];herbaceous agent/ae [Adverse Drug Reaction];herbaceous agent/dt [Drug Therapy];nonsteroid antiinflammatory agent;paracetamol/ae [Adverse Drug Reaction];paracetamol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];xenobiotic agent/ae [Adverse Drug Reaction];xenobiotic agent/dt [Drug Therapy],"Bernuau, J. R.;Durand, F.",2008,March,http://dx.doi.org/10.1097/MEG.0b013e3282f2bbf7,0,0,
1987,Treating mania in wilson's disease with lithium,,adult;article;bedtime dosage;bipolar disorder/dt [Drug Therapy];case report;drug substitution;drug withdrawal;extrapyramidal symptom/si [Side Effect];grandiose delusion;human;introspection;male;mania/dt [Drug Therapy];mood change;priority journal;psychologic assessment;psychomotor activity;slurred speech;social interaction;Wilson disease/dt [Drug Therapy];Young Mania Rating Scale;lithium/cb [Drug Combination];lithium/dt [Drug Therapy];olanzapine/ae [Adverse Drug Reaction];olanzapine/cb [Drug Combination];olanzapine/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trihexyphenidyl/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Loganathan, S.;Nayak, R.;Sinha, S.;Taly, A. B.;Math, S.;Varghese, M.",2008,November,,0,0,
1988,Copper transport systems are involved in multidrug resistance and drug transport,"Copper is an essential trace element and several copper containing proteins are indispensable for such processes as oxidative respiration, neural development and collagen remodeling. Copper metabolism is precisely regulated by several transporters and chaperone proteins. Copper Transport Protein 1 (CTR1) selectively uptakes copper into cells. Subsequently three chaperone proteins, HAH1 (human atx1 homologue 1), Cox17p and CCS (copper chaperone for superoxide dismutase) transport copper to the Golgi apparatus, mitochondria and copper/zinc superoxide dismutase respectively. Defects in the copper transporters ATP7A and ATP7B are responsible for Menkes disease and Wilson's disease respectively. These proteins transport copper via HAH1 to the Golgi apparatus to deliver copper to cuproenzymes. They also prevent cellular damage from an excess accumulation of copper by mediating the efflux of copper from the cell. There is increasing evidence that copper transport mechanisms may play a role in drug resistance. We, and others, found that ATP7A and ATP7B are involved in drug resistance against the anti-tumor drug cis-diamminedichloroplatinum (II) (CDDP). A relationship between the expression of ATP7A or ATP7B in tumors and CDDP resistance is supported by clinical studies. In addition, the copper uptake transporter CTR1 has also been reported to play a role in CDDP sensitivity. Furthermore, we have recently found that the effect of ATP7A on drug resistance is not limited to CDDP. Using an ex vivo drug sensitivity assay, the histoculture drug response assay (HDRA), the expression of ATP7A in human surgically resected colon cancer cells correlated with sensitivity to 7-ethyl-10-hydroxy-camptothecin (SN-38). ATP7Aoverexpressing cells are resistant to many anticancer drugs including SN-38, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), vincristine, paclitaxel, etoposide, doxorubicin (Dox), and mitoxantron. The mechanism by which ATP7A and copper metabolism modulate drug transport appears to involve modulation of drug cellular localization via modulation of the vesicle transport system. In ATP7A overexpressing cells, Dox accumulates in the Golgi apparatus. In contrast, in the parental cells, Dox is localized in the nuclei, where the target molecules of Dox, topoisomerase II and DNA, are found. Disruption of the intracellular vesicle transport system with monensin, a Na<sup>+</sup>/H<sup>+</sup> ionophore, induced the relocalization of Dox from the Golgi apparatus to the nuclei in the ATP7A overexpressing cells. These data suggested that ATP7A-related drug transport is dependent on the vesicle transport system. Thus copper transport systems play important roles in drug transport as well as in copper metabolism. Components of copper metabolism are therefore likely to include target molecules for the modulation of drug potency of not only anti-cancer agents but also of other drugs. © 2008 Bentham Science Publishers Ltd.",atp7a;atp7b;cddp;Copper transport;ctr1;Multidrug resistance;Vesicle transport;acidification;antineoplastic activity;cancer resistance;cancer survival;cell membrane transport;cellular distribution;collagen synthesis;colon cancer;concentration response;copper blood level;copper deficiency;copper metabolism;DNA repair;drug distribution;drug mechanism;drug potentiation;drug protein binding;drug selectivity;drug sensitivity;drug structure;drug targeting;drug transport;endocytosis;gene overexpression;Golgi complex;human;intracellular transport;nerve cell differentiation;protein expression;protein function;review;7-ethyl-10-hydroxycamptothecin/pd [Pharmacology];antineoplastic agent/an [Drug Analysis];antineoplastic agent/pd [Pharmacology];bafilomycin/it [Drug Interaction];bafilomycin A/it [Drug Interaction];cadmium;carboplatin;carrier protein/ec [Endogenous Compound];chaperone/ec [Endogenous Compound];cisplatin/an [Drug Analysis];cisplatin/pd [Pharmacology];cisplatin fluorescein conjugate/an [Drug Analysis];cisplatin fluorescein conjugate/pd [Pharmacology];concanamycin A/it [Drug Interaction];copper protein/ec [Endogenous Compound];copper transport protein 1/ec [Endogenous Compound];copper zinc superoxide dismutase;cyclohexymethylamino fluorescein/an [Drug Analysis];cyclohexymethylamino fluorescein/pd [Pharmacology];DNA topoisomerase (ATP hydrolysing)/ec [Endogenous Compound];dopamine beta monooxygenase;doxorubicin/an [Drug Analysis];doxorubicin/it [Drug Interaction];doxorubicin/pd [Pharmacology];etoposide/an [Drug Analysis];etoposide/pd [Pharmacology];human atx1 homologue 1 protein/ec [Endogenous Compound];irinotecan/pd [Pharmacology];Menkes protein/ec [Endogenous Compound];mitoxantrone;multidrug resistance protein 1/ec [Endogenous Compound];oxaliplatin/pd [Pharmacology];paclitaxel/pd [Pharmacology];unclassified drug;vincristine/pd [Pharmacology];Wilson disease protein/ec [Endogenous Compound],"Furukawa, T.;Komatsu, M.;Ikeda, R.;Tsujikawa, K.;Akiyama, S. I.",2008,December,http://dx.doi.org/10.2174/092986708786848479,0,0,
1989,Mania in a patient with Wilson's disease awaiting liver transplant,,adult;case report;decision making;distractibility;drug dose reduction;euphoria;extrapyramidal symptom/si [Side Effect];female;grandiose delusion;human;insomnia;letter;liver cirrhosis;liver transplantation;maintenance drug dose;mania/dt [Drug Therapy];portal hypertension;priority journal;psychomotor activity;Wilson disease/dt [Drug Therapy];haloperidol/ae [Adverse Drug Reaction];haloperidol/cb [Drug Combination];haloperidol/do [Drug Dose];haloperidol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];promethazine/cb [Drug Combination];promethazine/dt [Drug Therapy],"Varghese, S. T.;Narayanan, D.;Dinesh, D.",2008,November,,0,0,
1990,Copper & biological health,"Cu being a transition metal is ubiquitously engaged in biological systems to derive electrons through its participation in several enzymatic reactions. Upon bestowing the significance of Cu in biological systems, an elaborate mechanism is set forth by nature for maintaining Cu homeostasis. As a consequence, a wide variety of proteins viz., family of Cu bearing proteins, cuproenzymes, Cu transporters and Cu chaperone proteins have been manifested for enabling Cu to show its relevance in biological health. In addition, understanding the role of Cu in hepatic and neuronal functions and also in angiogenesis keeps progressing with the advent of novel molecular tools. The studies on genetic defects in Cu metabolism causing abnormalities are providing insights leading to the possible prognostic cues to alleviate the sufferings.",Ceruloplasmin;Cu carriers;Cu chaperones;Cu chelators;Cu metabolism;Cu transporters;Menkes disease;Oxygen binding Cu proteins;Wilson's disease;Alzheimer disease/et [Etiology];angiogenesis;bioavailability;chelation therapy;copper deficiency;copper metabolism;copper transport;dietary intake;endocytosis;endothelium cell;homeopathy;human;ion transport;Menkes syndrome/dt [Drug Therapy];metal binding;nonhuman;oxygenation;protein conformation;protein function;protein localization;review;scrapie/et [Etiology];tissue distribution;transcription regulation;tumor growth/et [Etiology];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];amyloid precursor protein/ec [Endogenous Compound];carrier protein/ec [Endogenous Compound];chaperone/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/to [Drug Toxicity];glutathione;monophenol monooxygenase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];prion protein/ec [Endogenous Compound];protein CopT/ec [Endogenous Compound];protein CopY/ec [Endogenous Compound];protein CopZ/ec [Endogenous Compound];protein ctr1/ec [Endogenous Compound];repressor protein/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];unclassified drug,"Krupanidhi, S.;Sreekumar, A.;Sanjeevi, C. B.",2008,,,0,0,
1991,Treating seizures in renal and hepatic failure,"Introduction: Renal and hepatic diseases cause seizures and patients with epilepsy may suffer from such diseases which change antiepileptic drugs (AEDs) metabolism. Objectives: To revise how seizures may be caused by metabolic disturbances due to renal or hepatic diseases, by their treatment or by comorbidities and how AEDs choice might be influenced by these conditions. Results: Seizures arise in renal failure due to toxins accumulation and to complications like sepsis, hemorrhage, malignant hypertension, pH and hydroelectrolytic disturbances. Hemodialysis leads to acute dysequilibrium syndrome and to dementia. Peritoneal dialysis may cause hyperosmolar non-ketotic coma. Post-renal transplant immunosupression is neurotoxic and cause posterior leukoencephalopathy, cerebral lymphoma and infections. Some antibiotics decrease convulsive thresholds, risking status epilepticus. Most commonly used AEDs in uremia are benzodiazepines, ethosuximide, phenytoin and phenobarbital. When treating epilepsy in renal failure, the choice of AED remains linked to seizure type, but doses should be adjusted especially in the case of hydrosoluble, low-molecular-weight, low-protein-bound, low apparent distribution volume AEDs. Hepatic failure leads to encephalopathy and seizures treated by ammonium levels and intestinal bacterial activity reductions, reversal of cerebral edema and intracranial hypertension. Phenytoin and benzodiazepines are usually ineffective. Seizures caused by post-hepatic immunosupression can be treated by phenytoin or levetiracetam. Seizures in Wilson's disease may result from D-penicillamine dependent piridoxine deficiency. Porphyria seizures may be treated with gabapentin, oxcarbazepine and levetiracetam. Hepatic disease changes AEDs pharmacokinetics and needs doses readjustments. Little liver-metabolized AEDs as gabapentin, oxcarbazepine and levetiracetam are theoretically more adequate. Conclusions: Efficient seizures treatment in renal and hepatic diseases requires adequate diagnosis of these disturbances and their comorbidities besides good knowledge on AEDs metabolism, their pharmacokinetic changes in such diseases, careful use of concomitant medications and AEDs serum levels monitoring.",Antiepileptic drugs;Hemodialysis;Hepatic failure;Immunosupression;Pharmacokinetics;Renal failure;Seizures;absence;albumin blood level;ammonia blood level;bleeding;body equilibrium;brain disease;brain edema;brain lymphoma;cancer radiotherapy;clinical practice;clinical trial;comorbidity;complex partial seizure;dementia;distribution volume;dose response;drug metabolism;electrolyte disturbance;epileptic state;grand mal seizure;HELLP syndrome;heme synthesis;hepatic encephalopathy;human;hyperosmolar coma;immunosuppressive treatment;induced abortion;infection;intestine flora;intracranial hypertension;kidney failure;kidney transplantation;liver failure;liver metabolism;liver transplantation;malignant hypertension;metabolic acidosis;metabolic disorder;molecular weight;myoclonus;neurotoxicity;peritoneal dialysis;pH;porphyria;posterior reversible encephalopathy syndrome;pyridoxine deficiency;renal replacement therapy;review;seizure/dt [Drug Therapy];seizure/et [Etiology];seizure/pc [Prevention];sepsis;simple partial seizure;solubility;tonic clonic seizure;uremia;Wilson disease;ammonia/ec [Endogenous Compound];antibiotic agent;benzodiazepine derivative;carbamazepine;cyclosporin/cb [Drug Combination];cytochrome P450/ec [Endogenous Compound];ethosuximide;etiracetam;gabapentin;lamotrigine;magnesium sulfate;methotrexate;OKT 3/cb [Drug Combination];oxcarbazepine;penicillamine;phenobarbital;phenytoin/ct [Clinical Trial];phenytoin/dt [Drug Therapy];prednisone/cb [Drug Combination];serum albumin/ec [Endogenous Compound];tacrolimus/cb [Drug Combination];tetrathiomolybdate ammonium;topiramate;toxin;trientine;valproic acid;vigabatrin;zinc,"De Lacerda, G. C. B.",2008,,,0,0,
1992,Inherited liver disease. [German],Elevated liver enzymes are common in clinical practice and hidden inherited liver diseases may play an important role to explain these abnormalities. In hereditary hemochromatosis the C282Y mutation yields to amplification of intestinal iron absorption despite of elevated total iron body stores. Number of gene mutations corresponding to enzymes along the hemebiosynthesis can lead to porphyrias - a heterogeneous group of inherited metabolic disorders. In Wilson disease different mutations cause a functional abnormal ATP7B transport protein responsible for impaired biliary copper excretion. Heterogeneous mutations were found in alpha 1 antitrypsin deficiency resulting in varying clinical expression patterns. In patients with Dubin Johnson Syndrome altered sequences of the MRP gene correspond to impaired biliary excretion of conjugated bilirubin. Early and sufficient diagnosis can help to improve the prognosis of affected patients since more and more options have been therapeutically established. The size of this overview is not large enough to address all inherited liver diseases. Therefore we selected cases and diseases recently diagnosed and treated in our practise. © 2008 Schattauer GmbH.,Alpha 1-antitrypsin deficiency;Dubin-Johnson syndrome;Hemochromatosis;Porphyrias;Wilson disease;acute intermittent porphyria/cn [Congenital Disorder];acute intermittent porphyria/di [Diagnosis];acute intermittent porphyria/et [Etiology];algorithm;alpha 1 antitrypsin deficiency/cn [Congenital Disorder];alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/et [Etiology];anamnesis;clinical feature;copper metabolism;Dubin Johnson syndrome/cn [Congenital Disorder];Dubin Johnson syndrome/di [Diagnosis];Dubin Johnson syndrome/et [Etiology];erythropoietic protoporphyria/cn [Congenital Disorder];erythropoietic protoporphyria/di [Diagnosis];erythropoietic protoporphyria/et [Etiology];gene mutation;hemochromatosis/cn [Congenital Disorder];hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];human;hypertension/co [Complication];hypertension/dt [Drug Therapy];infection/co [Complication];infection/dt [Drug Therapy];iron absorption;liver biopsy;liver disease/cn [Congenital Disorder];liver disease/di [Diagnosis];liver disease/et [Etiology];pain/co [Complication];pain/dt [Drug Therapy];pathophysiology;porphyria/cn [Congenital Disorder];porphyria/di [Diagnosis];porphyria/dt [Drug Therapy];porphyria/et [Etiology];porphyria cutanea tarda/cn [Congenital Disorder];porphyria cutanea tarda/di [Diagnosis];porphyria cutanea tarda/et [Etiology];review;tachycardia/co [Complication];tachycardia/dt [Drug Therapy];Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];acetylsalicylic acid/dt [Drug Therapy];alpha 1 antitrypsin/dt [Drug Therapy];alpha 1 antitrypsin/ec [Endogenous Compound];alpha tocopherol/dt [Drug Therapy];beta carotene/dt [Drug Therapy];bilirubin glucuronide/ec [Endogenous Compound];cephalosporin/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chloroquine/dt [Drug Therapy];chlorpromazine/dt [Drug Therapy];colestyramine/dt [Drug Therapy];endomysium antibody/ec [Endogenous Compound];gabapentin/dt [Drug Therapy];heme arginate/dt [Drug Therapy];losartan/dt [Drug Therapy];morphine derivative/dt [Drug Therapy];neostigmine/dt [Drug Therapy];ondansetron/dt [Drug Therapy];penicillamine/dt [Drug Therapy];penicillin derivative/dt [Drug Therapy];propranolol/dt [Drug Therapy];tetracycline derivative/dt [Drug Therapy];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Teubner, A.;Habeck, J. O.;Hempel, V.;Rossler, S.;Lindner, U.;Stolzel, U.",2008,June,,0,0,
1993,Approach to Wilson disease in children: Analysis of patients diagnosed and managed in Department of Pediatric and Infectious Diseases in Wroclaw (Poland) in last 10 years,"Introduction: Wilson disease (degeneratio hepato-lenticulatis) is a rare genetic disorder with autosomal recessive inheritance. The sequelae of impaired elimination is copper accumulation in liver, brain, kidneys, cornea and other organs with progressive deterioration of theirfunction. Wilson disease may adopt several clinical forms: hepatic, neurological or others. Hepatic form is the most common form for children and teenagers and was the only one observed in our patients. Signs and symptoms of Wilson disease are often unspecific: asthenia, anemia, dyspeptic symptoms, joint pains with abnormal liver function tests. Aim of study: The aim of the study was analysis of patients (age, sex, clinical and laboratory symptoms & signs, mode of diagnosis) managed in our department in last 10 years. Material and methods: Descriptive retrospective study; 8 children with Wilson disease attending the Department of Pediatric Infectious Diseases in Wroclaw, Poland, between 1997 and 2007 were enrolled. Results: We have managed 8 children (4 girls and 4 boys) with Wilson disease aged: 7-17 years, all with hepatic form. None of the children had Kayser-Fleischer ring. Disease was diagnosed with lowered serum ceruloplasmin level and increased copper urine excretion during differential diagnosis of chronic hepatitis in 6/8 or acute fulminate liver failure in 2/8 patients. Treatment with D-penicillamine in 7 patients or liver transplantation in one respectively was effective in all children. Conclusions: Wilson disease should be considered in any child with liver abnormalities of unexplained nature; in these children serum ceruloplasmin level and urinary copper excretion should be measured. Urinary copper excretion after D-penicillamine administration may also be helpful. The absence of Kayser-Fleischer rings does not exclude the diagnosis of Wilson disease and is typical for children. Screening of siblings of a patient with Wilson disease is mandatory. Copyright © 2008 Cornetis.",Children;Diagnosis;Poland;Symptoms;Wilson disease;adolescent;article;child;chronic hepatitis/di [Diagnosis];clinical article;clinical feature;controlled study;demography;differential diagnosis;female;human;infection;laboratory test;liver failure/di [Diagnosis];male;pediatrics;time;urinary excretion;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound],"Kuchar, E.;Szenborn, L.",2008,,,0,0,
1994,Orthomolecular treatment for schizophrenia: A review (part two),,adrenal disease;alternative medicine;Alzheimer disease;ascorbic acid deficiency;basal metabolic rate;cerebrospinal fluid;clinical trial;digestive system function disorder;electroconvulsive therapy;glucose blood level;glucose intolerance;heavy metal poisoning;hormonal therapy;human;hypothalamus hypophysis adrenal system;hypothyroidism/dt [Drug Therapy];lead poisoning;lipid peroxidation;malabsorption;mood disorder;neurotoxicity;nutritional deficiency;nutritional intolerance;oxidative stress;pathogenesis;pyridoxine deficiency;quality of life;recommended drug dose;review;RNA transcription;schizophrenia/co [Complication];schizophrenia/di [Diagnosis];schizophrenia/et [Etiology];thyroid function test;thyrotropin blood level;vitamin deficiency;Wilson disease;zinc deficiency;4 aminobutyric acid receptor blocking agent;adrenochrome/ec [Endogenous Compound];aluminum/to [Drug Toxicity];arsenic/to [Drug Toxicity];ascorbic acid/ec [Endogenous Compound];cadmium/to [Drug Toxicity];copper/to [Drug Toxicity];dessicated thyroid/dt [Drug Therapy];dopamine/ec [Endogenous Compound];free radical/ec [Endogenous Compound];hydrocortisone/ec [Endogenous Compound];lead/to [Drug Toxicity];liothyronine/ct [Clinical Trial];liothyronine/do [Drug Dose];liothyronine/dt [Drug Therapy];mercury/to [Drug Toxicity];messenger RNA/ec [Endogenous Compound];nicotinamide/ec [Endogenous Compound];noradrenalin/ec [Endogenous Compound];placebo;prealbumin/ec [Endogenous Compound];pyridoxine/ec [Endogenous Compound];thyroid hormone/dt [Drug Therapy];thyrotropin/ec [Endogenous Compound];thyroxine/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Pataracchia, R. J.",2008,Second Quarter,,0,0,
1995,Use of the molecular adsorbents recirculating system as a treatment for acute decompensated Wilson disease,"Acute decompensated Wilson disease presenting as fulminant liver failure is a life-threatening condition for which liver transplantation is the ultimate treatment. It is listed as a status 1 indication according to the United Network for Organ Sharing classification. A massive amount of copper released during the attack induces hemolytic anemia and acute renal failure. Conventional chelating therapy attempting to remove copper from the patient is not satisfactory because there is inadequate time for these drugs to take action and patients are usually oliguric. The Molecular Adsorbents Recirculating System (MARS) is a form of modified dialysis that removes putative albumin-bound toxins associated with liver failure. It is believed that extracorporeal albumin dialysate absorbs the circulating copper molecules that are trapped in the patient's circulation. We report 2 patients with acute decompensated Wilson disease treated with MARS. In the first case, the patient was started on MARS once conventional treatment failed. A significant amount of copper was removed from her circulatory system, and her condition stabilized afterwards. The treatment gained her extra time, and she was eventually bridged to liver transplantation. In the second case, the patient was started on MARS treatment early in the course of his illness, and his condition soon stabilized after the treatment. He was able to return to his home country for liver transplantation. In both cases, MARS was used as a means of preventing deterioration rather than salvaging devastation. In conclusion, MARS may confer benefits to patients with acute decompensated Wilson disease if it is started early in the course of illness. © 2008 AASLD.",abdominal distension;acute decompensated Wilson disease/th [Therapy];adolescent;adult;alanine aminotransferase blood level;albumin dialysis;alkaline phosphatase blood level;article;artificial ventilation;aspartate aminotransferase blood level;bilirubin blood level;cardiovascular system;case report;ceruloplasmin blood level;cholestasis;circulation;clinical assessment;clinical feature;controlled study;copper blood level;creatinine blood level;drug dose increase;early intervention;erythrocyte transfusion;female;follow up;human;intensive care unit;intravascular hemolysis;kidney function;liver failure/co [Complication];liver failure/su [Surgery];liver transplantation;male;oliguria/si [Side Effect];outcome assessment;priority journal;prothrombin time;reticulocyte count;risk reduction;treatment failure;urea nitrogen blood level;urine volume;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];lactulose/dt [Drug Therapy];nitrogen/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];urea/ec [Endogenous Compound];vitamin K group/dt [Drug Therapy],"Chiu, A.;Tsoi, N. S.;Fan, S. T.",2008,,http://dx.doi.org/10.1002/lt.21553,0,0,
1996,Hepatic Disorders Mildly to Moderately Affected by Pregnancy: Medical and Obstetric Management,"Hepatic, biliary, and pancreatic disorders are often complex and clinically challenging during pregnancy. Hepatic disorders can affect the pregnancy and vice versa. The differential diagnosis of hepatic diseases is particularly broad during pregnancy because it includes disorders related to, and unrelated to, pregnancy. This article discusses the physiologic effects of pregnancy on liver function; the differential diagnosis of hepatic findings during pregnancy; modifications of abdominal imaging and hepatobiliary endoscopic procedures during pregnancy; and the medical and obstetric management of hepatic, biliary, and pancreatic diseases that are mildly to moderately affected by pregnancy. © 2008 Elsevier Inc. All rights reserved.",acute cholecystitis/su [Surgery];acute pancreatitis/dt [Drug Therapy];autoimmune hepatitis/dt [Drug Therapy];biliary tract disease/di [Diagnosis];common bile duct stone/su [Surgery];congenital disorder/si [Side Effect];differential diagnosis;endoscopic retrograde cholangiopancreatography;hepatitis A;hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];hepatitis C;human;informed consent;liver abscess/dt [Drug Therapy];liver cell carcinoma;liver disease/di [Diagnosis];medical specialist;nuclear magnetic resonance imaging;obstetric care;pancreas disease/di [Diagnosis];physical examination;portal hypertension/dt [Drug Therapy];pregnancy;priority journal;review;symptomatology;teratogenicity/co [Complication];teratogenicity/si [Side Effect];Wilson disease/dt [Drug Therapy];X ray analysis;ampicillin;antibiotic agent/dt [Drug Therapy];azathioprine;beta adrenergic receptor blocking agent/dt [Drug Therapy];cephalosporin;clindamycin;gadolinium;hepatitis B vaccine/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];interferon;lamivudine/ae [Adverse Drug Reaction];lamivudine/dt [Drug Therapy];octreotide;penicillamine;pethidine/dt [Drug Therapy];ribavirin/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Cappell, M. S.",2008,July,http://dx.doi.org/10.1016/j.mcna.2008.03.003,0,0,
1997,Acute Liver Failure,"ALF is a rare but rapidly fatal disorder leading to jaundice, coagulopathy, and multisystem organ failure. Idiosyncratic drug-induced hepatotoxicity and acetaminophen are the most commonly identified causes in the U.S. Recognition of the syndrome requires a high index of suspicion. Despite aggressive care, these patients remain challenging medically and mortality is high. Cerebral edema with intracranial hypertension and infections remain the leading causes of death. Early intervention is crucial, and involvement of the liver transplant group with transfer to a specialty center will maximize survival. Liver transplantation remains the treatment of choice in patients who are not recovering and its use has markedly improved overall survival. Optimal prognostic survival models are lacking and many patients will ultimately die without transplantation. © 2008 Mosby, Inc. All rights reserved.",abdominal pain/si [Side Effect];acid base balance;acute liver failure of pregnancy;acute lung injury/co [Complication];alanine aminotransferase blood level;Amanita phalloides;aspartate aminotransferase blood level;autoimmune hepatitis/dt [Drug Therapy];bacterial infection/co [Complication];bilirubin blood level;blood clotting disorder/co [Complication];blood clotting disorder/si [Side Effect];brain edema/co [Complication];Budd Chiari syndrome;cardiovascular disease;Cytomegalovirus;drug fatality/si [Side Effect];drug metabolism;drug overdose;electrolyte disturbance/co [Complication];gastrointestinal hemorrhage/co [Complication];HELLP syndrome;hemodynamics;hepatic encephalopathy/co [Complication];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/si [Side Effect];hepatic encephalopathy/th [Therapy];Hepatitis A virus;Hepatitis B virus;Hepatitis delta virus;Hepatitis E virus;Herpes simplex virus;human;hyperbilirubinemia/si [Side Effect];hypoglycemia/co [Complication];hypoxia;induced hypothermia;kidney failure/co [Complication];kidney failure/et [Etiology];kidney failure/si [Side Effect];kidney failure/th [Therapy];lactic acidosis/si [Side Effect];liver biopsy;liver disease/si [Side Effect];liver failure/di [Diagnosis];liver failure/et [Etiology];liver failure/su [Surgery];liver injury/si [Side Effect];liver tenderness/si [Side Effect];liver toxicity/dt [Drug Therapy];liver transplantation;lung infection/co [Complication];malaise/si [Side Effect];mushroom poisoning;mycosis/co [Complication];nausea/si [Side Effect];prognosis;prothrombin time;renal replacement therapy;review;sepsis/co [Complication];side effect/si [Side Effect];thrombocytopenia/co [Complication];Varicella zoster virus;vomiting/si [Side Effect];Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];acetylcysteine/pd [Pharmacology];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];carbon tetrachloride/to [Drug Toxicity];chloroform/to [Drug Toxicity];corticosteroid/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];paracetamol/do [Drug Dose];paracetamol/pk [Pharmacokinetics];penicillamine/dt [Drug Therapy];phenytoin/dt [Drug Therapy];tannin/to [Drug Toxicity];thiopental/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Larson, A. M.",2008,July,http://dx.doi.org/10.1016/j.disamonth.2008.03.008,0,0,
1998,Sarar technology for the application of copper-64 in biology and materials science,"This review provides an overview of the synthesis and metal complexation chemistry of the nitrogen and sulphur donor bicyclic ligands or cages, and the key criteria that led to the design of sarar for the application for <sup>64</sup>Cu(II). Aspects of the high yielding synthesis of sarar and strategies for its conjugation to a range of antibodies for targeting colorectal cancer, neuroblastoma and melanoma are described. Free and conjugated to proteins sarar can complex <sup>64</sup>Cu(II) rapidly at room temperature and quantitatively; the latter leading to products of high specific activity and purity. The full occupation of the <sup>64</sup>Cu(II) ions 6 coordination sites by the sarar cage prevents the ready exchange of the <sup>64</sup>Cu(II) from the cage and is the rational for the extraordinary thermodynamic and kinetic stability of <sup>64</sup>Cu(II) labelled sarar and its conjugates. It's in vivo stability is further highlighted by the low uptake and retention of <sup>64</sup>Cu-sarar-conjugated antibodies in the liver. Finally, the prospects for the use of the sarar technology in the materials science arena for probing solid liquid interfaces, in particular, the quantification of functional groups on microspheres and in the engineering of novel materials are discussed.",Cooper;Molecular imaging;Technology;colorectal cancer/di [Diagnosis];complex formation;conference paper;drug clearance;drug design;drug purity;drug structure;drug synthesis;human;intoxication/dt [Drug Therapy];melanoma/di [Diagnosis];metal binding;molecular interaction;molecular stability;nanotechnology;neuroblastoma/di [Diagnosis];nonhuman;oxidation reduction potential;physical chemistry;positron emission tomography;room temperature;thermodynamics;Wilson disease/dt [Drug Therapy];diamsar cobalt complex/an [Drug Analysis];diamsar copper complex/an [Drug Analysis];diamsar copper complex/cm [Drug Comparison];diamsar copper complex/dt [Drug Therapy];diamsar copper complex/pk [Pharmacokinetics];diamsar cu 64/an [Drug Analysis];diamsar cu 64/pk [Pharmacokinetics];dinosar cobalt complex/an [Drug Analysis];microsphere co 57;microsphere cu 64;monoclonal antibody 14.G2a sarar cu 64/pk [Pharmacokinetics];monoclonal antibody B.72.3 pentetate in 111/cm [Drug Comparison];monoclonal antibody B.72.3 pentetate in 111/pk [Pharmacokinetics];monoclonal antibody B.72.3 sarar cu 64/an [Drug Analysis];monoclonal antibody B.72.3 sarar cu 64/cm [Drug Comparison];monoclonal antibody B.72.3 sarar cu 64/pk [Pharmacokinetics];monoclonal antibody ch14.18 sarar cu 64/pk [Pharmacokinetics];nitrogen;penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];radioactive microsphere;radiopharmaceutical agent/an [Drug Analysis];radiopharmaceutical agent/cm [Drug Comparison];sarar co 57/an [Drug Analysis];sarar co 57/cm [Drug Comparison];sarar cu 64/an [Drug Analysis];sarar cu 64/cm [Drug Comparison];sarar cu 64/pk [Pharmacokinetics];sarar ni 57/an [Drug Analysis];sarar ni 57/cm [Drug Comparison];sarcophagine cobalt complex/an [Drug Analysis];sarcophagine copper complex/an [Drug Analysis];sarcophagine copper complex/cm [Drug Comparison];sarcophagine copper complex/dt [Drug Therapy];sarcophagine copper complex/pk [Pharmacokinetics];sulfur;tracer/an [Drug Analysis];tracer/cm [Drug Comparison],"Smith, S. V.",2008,June,,0,0,
1999,Abnormal antisaccades and smooth pursuit eye movements in patients with Wilson's disease,"Neurological symptoms in Wilson's disease (WD) may include oculomotor abnormalities. However, to date, eye movements in WD patients were rarely investigated and the data concerning this issue are sparse. The purpose of this study was to evaluate reflexive and voluntary eye movements in WD patients. We examined horizontal saccadic and smooth pursuit eye movements using infra-red oculography in 50 WD patients, including 29 neurologically symptomatic (WDn) and 21 asymptomatic ones (WDa), and in 29 healthy controls. We found statistically significant increase in mean antisaccadic latency (378 ms) and in mean antisaccadic error rate (22.5) in the WDn group, when compared with WDa group (317 ms and 9.1, respectively) and controls (318 ms and 9.7, respectively). In contrast, there were no statistically significant differences in mean latency of prosaccades and in size of the gap effect. Patients with neurological manifestations had also abnormal smooth pursuit - increased number of saccadic intrusions (mean: 8.6) and decreased gain (mean: 0.69) comparing with WDa patients (4.1 and 0.83, respectively) and controls (2.2 and 0.91, respectively). The data suggest that WD is associated both with impairment of voluntary control of saccades and with disturbed smooth pursuit eye movements while re.exive saccades seem to be preserved. © 2008 Movement Disorder Society.",Antisaccades;Basal ganglia;Eye movements;Smooth pursuit;Wilson's disease;adult;article;clinical article;controlled study;eye movement disorder;female;human;infrared oculography;latent period;male;priority journal;saccadic eye movement;smooth pursuit eye movement;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Lesniak, M.;Czlonkowska, A.;Seniow, J.",2008,30 Oct,http://dx.doi.org/10.1002/mds.22276,0,0,
2000,Wilson's disease: Appreciable improvement of sub-cortical white matter abnormalities after copper chelating treatment: Five years follow-up,"Severe sub-cortical white matter abnormalities are unusual features in Wilson's disease and are reported to be poorly or not responsive to copper chelating therapy or to be worsened by it. We report on a 12-year-old boy with Wilson's disease and extensive sub-cortical white matter involvement. After five years of copper chelating therapy, an appreciable improvement of these lesions was obtained. The physiopathology of these unusual cerebral white matter abnormalities is discussed. © Georg Thieme Verlag KG Stuttgart. New York.",Copper chelating therapy;Sub-cortical white matter;Wilson's disease;article;bipolar disorder;blood cell count;bradykinesia;brain atrophy;brain damage;case report;clinical feature;computer assisted tomography;copper blood level;diet restriction;dystonia;echography;esophagus varices;family history;follow up;human;hypersalivation;image display;language disability;liver atrophy;male;motor dysfunction;neuropathology;oral bleeding/co [Complication];oral bleeding/dt [Drug Therapy];portal hypertension;priority journal;school child;splenomegaly;urinary excretion;vein rupture;white matter;Wilson disease/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];propranolol/dt [Drug Therapy];vitamin B group/dt [Drug Therapy],"Larnaout, A.;Ammar, N.;Mourad, Z.;Naji, S.;Hentati, F.",2008,June,http://dx.doi.org/10.1055/s-0028-1085464,0,0,
2001,"Resurge of dysarthria, muscular dystrophy, tremor dystonia and so on in the patients with Wilson's disease after discontinuation of copper chelating agents. [Japanese]","Wilson's disease is autosomal recessive hereditary disorder and also occurred abnormal copper (Cu) metabolism due to dysfunction of ATP7B enzyme, so that excessive Cu contents are accumulated in the tissues. Ionic Cu binds with methallthionine, making the cell damage by oxidative oxygen. It is in fact that tissues are injured due to having the hereditary nature unless Cu deposits in tissues must be removed. Among seven cases being continuously administrated D-penicillamin and zinc acetate alternately each week, at the time of the initial symptoms such as dysarthria, athetose and so on in the childhood, all cases were improved after treatment of Cu-chelating agents. But four cases quitted administration of these drugs in adulthood were suffered from the severely slurred speech, dystonia, ataxia, liver cirrhosis, renal tubular damage and so on. Four cases were resurged the symptoms, although treated with the same dose of Cu-chelating agents and simultaneously conducted physical and language therapies, symptoms did not get betterment but were in vain. During long observation of reciprocal relation of symptoms and treatment of Cu-chelating agents in patients with Wilson's disease, it leads to a conclusion that patients with symptoms in Wilson's disease should be obliged to take a life long treatment with Cu-chelating agents to help remove excessive Cu deposit from tissues.",D-penicillamine;Dysarthria;Resurge of Wilson's disease;Therapy of Wilson's disease;Tremor;article;ataxia/dt [Drug Therapy];ataxia/th [Therapy];chelation therapy;clinical article;copper metabolism;disease severity;drug efficacy;dysarthria/dt [Drug Therapy];dysarthria/th [Therapy];dystonia/dt [Drug Therapy];dystonia/th [Therapy];human;kidney tubule damage;liver cirrhosis;long term care;muscular dystrophy/dt [Drug Therapy];muscular dystrophy/th [Therapy];physiotherapy;recurrent disease/dt [Drug Therapy];recurrent disease/th [Therapy];repeated drug dose;slurred speech/dt [Drug Therapy];slurred speech/th [Therapy];speech therapy;symptom;tremor/dt [Drug Therapy];tremor/th [Therapy];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];chelating agent/do [Drug Dose];chelating agent/dt [Drug Therapy];copper ion;penicillamine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Takase, T.;Konishi, M.;Miwa, R.;Kunisue, K.;Furui, T.;Sakai, K.;Hisari, A.;Fujino, F.;Tsuda, H.;Kamishima, T.;Kurasawa, S.;Tsubota, Y.;Nakamura, M.;Ota, K.",2008,,,0,0,
2002,The risks of free copper in the body and the development of useful anticopper drugs,"Some of the implications are that Alzheimer's disease and other diseases of neurodegeneration and fibrotic, inflammatory, and autoimmune diseases may be treatable by lowering the availability of free copper. People in the general population may wish to take steps to lower their free copper levels and, in particular, to abstain from taking copper supplements and ingesting significant amounts of copper in drinking water. © 2008 Wolters Kluwer Health Lippincott Williams & Wilkins.",Alzheimer's disease;Free copper;Tetrathiomolybdate;Wilson's disease;Alzheimer disease/dt [Drug Therapy];amyotrophic lateral sclerosis/dt [Drug Therapy];anemia/si [Side Effect];autoimmunity;blood brain barrier;circulation;clinical trial;cognitive defect/dt [Drug Therapy];copper blood level;copper overload/co [Complication];copper overload/dt [Drug Therapy];copper overload/et [Etiology];copper overload/si [Side Effect];dietary intake;disease exacerbation/si [Side Effect];drug dose reduction;drug effect;drug inhibition;drug overdose;experimental model;experimental mouse;fibrosis;gastrointestinal symptom/si [Side Effect];heart injury/dt [Drug Therapy];heart injury/pc [Prevention];human;inflammation;leukopenia/si [Side Effect];lipid diet;liver;liver cirrhosis/dt [Drug Therapy];low drug dose;mineral intake;nerve degeneration/dt [Drug Therapy];neurologic disease/si [Side Effect];nonhuman;pathogenesis;review;risk assessment;toxicity/co [Complication];toxicity/dt [Drug Therapy];toxicity/et [Etiology];treatment duration;unspecified side effect/si [Side Effect];vitamin supplementation;Wilson disease/dt [Drug Therapy];zinc deficiency/pc [Prevention];anticopper agent/ct [Clinical Trial];anticopper agent/dt [Drug Therapy];anticopper agent/po [Oral Drug Administration];anticopper agent/pd [Pharmacology];apolipoprotein E4/ec [Endogenous Compound];beta secretase/ec [Endogenous Compound];bleomycin/dt [Drug Therapy];blocking agent/ct [Clinical Trial];blocking agent/dt [Drug Therapy];blocking agent/pd [Pharmacology];ceruloplasmin/ec [Endogenous Compound];copper/ae [Adverse Drug Reaction];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper/po [Oral Drug Administration];copper/pk [Pharmacokinetics];copper 64/to [Drug Toxicity];doxorubicin/do [Drug Dose];doxorubicin/dt [Drug Therapy];doxorubicin/to [Drug Toxicity];drinking water;interleukin 1beta/ec [Endogenous Compound];interleukin 2/ec [Endogenous Compound];isoprostane/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];multivitamin/dt [Drug Therapy];paracetamol/do [Drug Dose];paracetamol/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];transforming growth factor beta/ec [Endogenous Compound];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];tumor necrosis factor alpha/ec [Endogenous Compound];unclassified drug;zinc/ae [Adverse Drug Reaction];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Brewen, G. J.",2008,November,http://dx.doi.org/10.1097/MCO.0b013e328314b678,0,0,
2003,Triethylenetetramine and metabolites: Levels in relation to copper and zinc excretion in urine of healthy volunteers and type 2 diabetic patients,"Triethylenetetramine (TETA), a selective Cu<sup>II</sup>-chelator used in the treatment of Wilson's disease, is now undergoing clinical trials for the treatment of heart failure in diabetes. Despite decades of clinical use, knowledge of its pharmacology in human subjects remains incomplete. Here, we first used liquid chromatography-mass spectrometry (LC-MS) to detect and identify major metabolites of TETA in human plasma and urine, and then used this method to measure concentrations of TETA and its metabolites in the urine of healthy and diabetic subjects who were administered increasing doses (300, 600, 1200, and 2400 mg) of TETA orally. Twenty-four-hour urine collections were performed before and after dosing participants. Two major metabolites of TETA were detected in human urine, N1-acetyltriethylenetetramine (MAT) and N <inf>1</inf>,N<inf>10</inf>-diacetyltriethylenetetramine, the latter being novel. Both metabolites were verified with synthetic standards by LC-MS. The proportion of unchanged TETA excreted as a fraction of total urinary drug-derived molecules was significantly higher in healthy than in matched diabetic subjects, consistent with a higher rate of TETA metabolism in the latter. TETA-evoked increases in urinary Cu excretion in nondiabetic subjects were more closely correlated with parent drug concentrations than in diabetic subjects, whereas, by contrast, urinary Cu was more closely associated with the sum of TETA and MAT. These findings are consistent with the hypothesis that MAT could play a significant role in the molecular mechanism by which TETA extracts Cu<sup>II</sup> from the systemic compartment in diabetic subjects. Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics.","adult;aged;article;clinical trial;controlled clinical trial;controlled study;drug blood level;drug dose increase;drug excretion;drug metabolism;drug urine level;heart failure;human;liquid chromatography;male;mass spectrometry;non insulin dependent diabetes mellitus;patient compliance;priority journal;urinalysis;urinary excretion;copper;drug metabolite/cr [Drug Concentration];drug metabolite/pk [Pharmacokinetics];n1 acetyltriethylenetetramine/cr [Drug Concentration];n1 acetyltriethylenetetramine/pk [Pharmacokinetics];n1,n10 diacetyltriethylenetetramine/cr [Drug Concentration];n1,n10 diacetyltriethylenetetramine/pk [Pharmacokinetics];trientine/cr [Drug Concentration];trientine/po [Oral Drug Administration];trientine/pk [Pharmacokinetics];unclassified drug;zinc","Lu, J.;Chan, Y. K.;Gamble, G. D.;Poppitt, S. D.;Othman, A. A.;Cooper, G. J. S.",2007,February,http://dx.doi.org/10.1124/dmd.106.012922,0,0,
2004,"The copper chelator, D-penicillamine, does not attenuate MPTP induced dopamine depletion in mice","In MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-hydroxydopamine induced dopaminergic neurotoxicity and Parkinson's disease iron accumulates in substantia nigra pars compacta which has been suggested to participate in oxidative stress induced neurodegeneration. Pretreatment with iron chelators desferal, clioquinol, VK-28 and M30 are neuroprotective in both models. To determine the specificity of chelation neuroprotective activity we have examined the effect of D-penicillamine, a relatively specific copper chelator, in the mice model of MPTP-induced dopamine depletion. Our studies show that D-penicillamine, employed for removal of copper in Wilson disease is relatively weak in preventing dopaminergic neurotoxicity induced by MPTP, as compared to iron chelators previously studied. The results indicate that for prevention of MPTP-induced dopamine depletion and dopamine neurodegeneration, iron rather than copper chelation may be more effective and specific. © 2006 Springer-Verlag.","Copper;D-penicillamine;Iron;Metal chelator;mptp;Neuroprotection;Parkinson's disease;animal experiment;animal model;article;chelation;controlled study;dopaminergic activity;male;mouse;nerve degeneration;neurotoxicity;nonhuman;priority journal;Wilson disease;1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine/to [Drug Toxicity];acetylcysteine/ip [Intraperitoneal Drug Administration];acetylcysteine/pd [Pharmacology];apomorphine/cm [Drug Comparison];apomorphine/pd [Pharmacology];chelating agent/pd [Pharmacology];copper chelating agent/cm [Drug Comparison];copper chelating agent/pd [Pharmacology];dopamine/ec [Endogenous Compound];iron chelating agent/cm [Drug Comparison];iron chelating agent/pd [Pharmacology];penicillamine/cm [Drug Comparison];penicillamine/pd [Pharmacology];salicylic acid/ip [Intraperitoneal Drug Administration];salicylic acid/pd [Pharmacology];unclassified drug","Youdim, M. B. H.;Grunblatt, E.;Mandel, S.",2007,February,http://dx.doi.org/10.1007/s00702-006-0499-1,0,0,
2005,Clinicopathologic findings in 35 children with Wilson disease,"Background and Aim: Wilson disease is a rare autosomal recessive disorder of copper metabolism. Wilson disease is the most common metabolic cause of fulminant hepatic failure in children over the age of 3 years. The aim of this study was to find the major clinical & pathologic findings of Wilson disease in children in Tehran. Patients and Methods: This retrospective study was carried out in the mofid children's hospital. Thirty five patients suffering from Wilson disease were studied. Ceruloplasmin level below 20mg/dl and urinary copper excretion level above 100mug/24hr were considered as the inclusion criteria. Results: Of the patients, 20 cases were males and 15 were females with average age of 9 years. The most patients were in 8-9 and 10-11 years age group with 37% and 20%, respectively. Hepatic involvement was confirmed in 100% of patients. Jaundice was seen in 20 patients (57%), abdominal enlargement together in 20 patients (57%), and encephalopathy in 9 patients (26%). Serum copper was reduced in 100% and low-serum ceroluplasmin in 100%, increased urinary copper excretion in %97, increased AST & ALT in 100%, increased PT was in 94% patients, anemia was found in 100%, leucopenia in 14%, and thrombocytopenia was seen in 71% of patients. In this study, 37% of patients had neurological symptoms such as tremor, ataxia, difficulty in speech and delayed education. 32 patients had undergone ophthalmic examination and 62% showed KF ring in their ophtalmoscopy. Conclusion: According to this study, hepatic and neurologic involvement is the most consistent finding in the Wilson disease. Most patients were in the age's group of 8-9 and 10-11. © 2007 DAR Publisher/ University of Jordan. All Rights Reserved.",Liver;Wilson disease;anemia;article;ataxia;autosomal recessive disorder;brain disease;clinical article;clinical assessment;clinical examination;copper metabolism;eye examination;female;histopathology;human;Iran;jaundice;leukopenia;liver disease;liver failure;male;neurologic disease;ophthalmoscopy;patient selection;rare disease;retrospective study;school child;speech disorder;thrombocytopenia;tremor;urinary excretion;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Imanzadeh, F.;Sayyari, A. A.;Adib, F.;Javaherizadeh, H.;Fattah, S.",2007,September,,0,0,
2006,Liver transplantation,"Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. © 2007 Elsevier Masson.",Hepatocellular carcinoma;Immunosuppression;Liver transplantation;Living donor;Piggyback;Recipient outcome;Split-liver;adjuvant therapy;alcohol liver cirrhosis;alpha 1 antitrypsin deficiency/su [Surgery];article;bile duct carcinoma/dt [Drug Therapy];bile duct carcinoma/su [Surgery];cataract/si [Side Effect];chronic liver disease/su [Surgery];Cushing syndrome/si [Side Effect];diarrhea/si [Side Effect];donor selection;dyslipidemia/si [Side Effect];gingiva hyperplasia/si [Side Effect];glaucoma/si [Side Effect];glucose intolerance/si [Side Effect];hemochromatosis/dt [Drug Therapy];hemochromatosis/ep [Epidemiology];hemochromatosis/su [Surgery];hepatitis B/dt [Drug Therapy];hepatitis C/ep [Epidemiology];hirsutism/si [Side Effect];human;hypertension/si [Side Effect];immunosuppressive treatment;intrahepatic cholestasis;liver cirrhosis/et [Etiology];liver failure/et [Etiology];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver metastasis/su [Surgery];liver resection;liver tumor;metabolic disorder;moon face/si [Side Effect];muscle mass;nephrotoxicity/si [Side Effect];obesity/si [Side Effect];osteoporosis/si [Side Effect];phlebotomy;postoperative complication/co [Complication];primary biliary cirrhosis/dt [Drug Therapy];primary biliary cirrhosis/su [Surgery];primary sclerosing cholangitis/dt [Drug Therapy];priority journal;psychosis/si [Side Effect];side effect/si [Side Effect];stria/si [Side Effect];surgical technique;tremor/si [Side Effect];viremia/dt [Drug Therapy];weight gain;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adefovir/dt [Drug Therapy];alkylating agent/dt [Drug Therapy];allopurinol;antineoplastic agent/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];azathioprine/pk [Pharmacokinetics];basiliximab/dt [Drug Therapy];carbamazepine;cimetidine;corticosteroid/cb [Drug Combination];corticosteroid/dt [Drug Therapy];corticosteroid/iv [Intravenous Drug Administration];corticosteroid/pd [Pharmacology];cortisone/dt [Drug Therapy];cyclosporin A/ae [Adverse Drug Reaction];cyclosporin A/cm [Drug Comparison];cyclosporin A/dt [Drug Therapy];cyclosporin A/pk [Pharmacokinetics];daclizumab/dt [Drug Therapy];erythromycin;fluconazole;glucocorticoid/ae [Adverse Drug Reaction];glucocorticoid/dt [Drug Therapy];immunoglobulin/dt [Drug Therapy];interferon/dt [Drug Therapy];lamivudine/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester/ae [Adverse Drug Reaction];mycophenolic acid 2 morpholinoethyl ester/dt [Drug Therapy];mycophenolic acid 2 morpholinoethyl ester/pd [Pharmacology];OKT 3/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenobarbital;phenytoin;rapamycin/ae [Adverse Drug Reaction];rapamycin/dt [Drug Therapy];rapamycin/pd [Pharmacology];tacrolimus/ae [Adverse Drug Reaction];tacrolimus/cm [Drug Comparison];tacrolimus/dt [Drug Therapy];tacrolimus/pk [Pharmacokinetics];thymocyte antibody/cb [Drug Combination];thymocyte antibody/dt [Drug Therapy];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];verapamil,"Rossi, M.;Mennini, G.;Lai, Q.;Ginanni Corradini, S.;Drudi, F. M.;Pugliese, F.;Berloco, P. B.",2007,March,http://dx.doi.org/10.1016/j.jus.2007.02.006,0,0,
2007,Perspectives for gene therapy of Wilson disease,"Wilson disease is a rare autosomal-recessive copper overload disorder due to mutations of the Wilson disease gene ATP7B. The disease typically manifests at late childhood or in young adults with hepatic and/or neurological symptoms. Being fatal without medical treatment or liver transplantation the long-term outcome of Wilson disease depends on the adherence to an effective treatment. Because current medical treatment options are not effective in all Wilson disease patients and adherence to therapy is a problem, gene therapy might represent an alternative curative future therapy. In the rat model of Wilson disease adenoviral and lentiviral gene transfer studies could prove that viral gene transfer is therapeutically effective and can reverse clinical symptoms. However, both approaches were limited by a more or less transient transgene expression. As several tactics can be used to overcome these current limitations, gene therapy approaches may become more efficient than standard medical treatment for Wilson disease in the future. This review discusses both, existing vectors and strategies and prospective developments towards liver-directed gene therapy, although there is still a long way to go until gene therapy can be used for safe treatment of Wilson disease in humans. © 2007 Bentham Science Publishers Ltd.",AAV vectors;ATP7B cDNA;ATP7B gene;Gene therapy;Long-Evans Cinnamon rat;autosomal recessive disorder;ceruloplasmin blood level;combined immunodeficiency;fatality;gene expression;gene mutation;gene transfer;human;liver failure/su [Surgery];liver transplantation;neurologic disease;nonhuman;nonviral gene therapy;prognosis;review;safety;symptom;T cell leukemia/co [Complication];viral gene delivery system;Wilson disease/dt [Drug Therapy];adenovirus vector;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];lentivirus vector;penicillamine/dt [Drug Therapy];retrovirus vector;trientine/dt [Drug Therapy];Wilson disease protein/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Merle, U.;Stremmel, W.;Encke, J.",2007,June,http://dx.doi.org/10.2174/156652307780859053,0,0,
2008,Zinc and the liver: An active interaction,"Zinc is an essential trace element, exerting important antioxidant, anti-inflammatory, and antiapoptotic effects. It affects growth and development and participates in processes such as aging and cancer induction. The liver is important for the regulation of zinc homeostasis, while zinc is necessary for proper liver function. Decreased zinc levels have been implicated in both acute and chronic liver disease states, and zinc deficiency has been implicated in the pathogenesis of liver diseases. Zinc supplementation offers protection in experimental animal models of acute and chronic liver injury, but these hepatoprotective properties have not been fully elucidated. In the present review, data on zinc homeostasis, its implication in the pathogenesis of liver diseases, and its effect on acute and chronic liver diseases are presented. It is concluded that zinc could protect against liver diseases, although up to now the underlying pathophysiology of zinc and liver interactions have not been defined. © 2006 Springer Science+Business Media, Inc.",Acute;Chronic;Hepatocellular carcinoma;Injury;Liver;Zinc;alcohol liver cirrhosis;alcohol liver disease;chronic liver disease;clinical trial;fatty liver;hemochromatosis;hepatic encephalopathy/dt [Drug Therapy];hepatitis;homeostasis;human;liver cell carcinoma;liver cirrhosis;liver disease;liver failure;liver fibrosis/dt [Drug Therapy];liver injury/dt [Drug Therapy];liver injury/pc [Prevention];metabolism;nonhuman;pathogenesis;pathophysiology;primary biliary cirrhosis;priority journal;review;virus hepatitis/et [Etiology];Wilson disease/dt [Drug Therapy];zinc deficiency;antifibrotic agent;chelating agent/dt [Drug Therapy];colchicine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];prostaglandin E2/cm [Drug Comparison];tetrathiomolibdate/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;zinc/ct [Clinical Trial];zinc/cm [Drug Comparison];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc/pd [Pharmacology],"Stamoulis, I.;Kouraklis, G.;Theocharis, S.",2007,July,http://dx.doi.org/10.1007/s10620-006-9462-0,0,0,
2009,The structure and function of heavy metal transport P<inf>1B</inf>-ATPases,"P<inf>1B</inf>-type ATPases transport heavy metals (Cu<sup>+</sup>, Cu <sup>2+</sup>, Zn<sup>2+</sup>, Co<sup>2+</sup>, Cd<sup>2+</sup>, Pb <sup>2+</sup>) across membranes. Present in most organisms, they are key elements for metal homeostasis. P<inf>1B</inf>-type ATPases contain 6-8 transmembrane fragments carrying signature sequences in segments flanking the large ATP binding cytoplasmic loop. These sequences made possible the differentiation of at least four P<inf>1B</inf>-ATPase subgroups with distinct metal selectivity: P<inf>1B-1</inf>: Cu<sup>+</sup>, P<inf>1B-2</inf>: Zn <sup>2+</sup>, P<inf>1B-3</inf>: Cu<sup>2+</sup>, P<inf>1B-4</inf>: Co <sup>2+</sup>. Mutagenesis of the invariant transmembrane Cys in H6, Asn and Tyr in H7 and Met and Ser in H8 of the Archaeoglobus fulgidus Cu<sup>+</sup>-ATPase has revealed that their side chains likely coordinate the metals during transport and constitute a central unique component of these enzymes. The structure of various cytoplasmic domains has been solved. The overall structure of those involved in enzyme phosphorylation (P-domain), nucleotide binding (N-domain) and energy transduction (A-domain), appears similar to those described for the SERCA Ca<sup>2+</sup>-ATPase. However, they show different features likely associated with singular functions of these proteins. Many P<inf>1B</inf>-type ATPases, but not all of them, also contain a diverse arrangement of cytoplasmic metal binding domains (MBDs). In spite of their structural differences, all N- and C-terminal MBDs appear to control the enzyme turnover rate without affecting metal binding to transmembrane transport sites. In addition, eukaryotic Cu<sup>+</sup>-ATPases have multiple N-MBD regions that participate in the metal dependent targeting and localization of these proteins. The current knowledge of structure-function relationships among the different P<inf>1B</inf>-ATPases allows for a description of selectivity, regulation and transport mechanisms. Moreover, it provides a framework to understand mutations in human Cu<sup>+</sup>-ATPases (ATP7A and ATP7B) that lead to Menkes and Wilson diseases. © 2007 Springer Science+Business Media, Inc.",Cadmium;Cobalt;Copper;Heavy metals;Membrane transport;P-type ATPases;Zinc;Archaeoglobus fulgidus;carboxy terminal sequence;cell membrane transport;conference paper;DNA flanking region;DNA sequence;enzyme localization;enzyme phosphorylation;enzyme regulation;homeostasis;Menkes syndrome/et [Etiology];nucleotide binding site;protein domain;protein localization;protein targeting;site directed mutagenesis;Wilson disease/et [Etiology];adenosine triphosphatase;dna;enzyme;heavy metal;lead,"Arguello, J. M.;Eren, E.;Gonzalez-Guerrero, M.",2007,June,http://dx.doi.org/10.1007/s10534-006-9055-6,0,0,
2010,Elastosis perforans serpiginosa induced by D-penicillamine. [Italian],"Elastosis perforans serpiginosa (EPS) is a rare complication of D-penicillamine therapy. It has been reported in patients with Wilson disease, cystinuria and rheumatoid arthritis after long-term high-dose therapy. We report the case of a 29-year-old man with Wilson's disease who had been treated with D-penicillamine in the past 11 years, and who presented with a 9-month history of pruritic erythematous papules on both sides of the neck. Physical examination revealed multiple, firm, keratotic, umbilicated pink lesions arranged in an arciform pattern. Histological examination of a biopsy specimen showed clumps of elastic fibers being extruded through an acanthotic epidermis with a central invagination. The clinical and histologic features of EPS and its pathogenesis are discussed.",D-penicillamine;Elastosis perforans serpiginosa (EPS);adult;article;case report;drug induced disease;edema;elastosis perforans serpiginosa/et [Etiology];histopathology;human;human tissue;male;papule;pathogenesis;physical examination;pruritus;skin biopsy;skin defect;skin disease/si [Side Effect];skin disease/et [Etiology];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Scuderi, L.;Francesconi, L.;Dinotta, F.;De Pasquale, R.;Nasca, M. R.;Micali, G.",2007,September/December,,0,0,
2011,"Reversible precipitation of bovine serum albumin by metal ions and synthesis, structure and reactivity of new tetrathiometallate chelating agents","Independent research is an important component of any undergraduate chemistry program. This article reports the findings of two of many undergraduate research projects directed by Ed Stiefel in the hopes that the results will be inspiring and useful to the scientific community. The neurological disorders associated with insufficient copper in Menkes disease and an excess of copper in Wilson's disease are well established; however, recent evidence suggests that copper may also be involved in other disorders, such as Alzheimer's, angiogenesis, and prion diseases. The exact role of copper, however, is uncertain. This study examines the role of copper and zinc in the formation of protein deposits and the chelation and removal of the metal ions to reverse the process. The bovine serum albumin (BSA) protein forms a precipitate after the addition of approximately 6 copper(II) atoms or 8 zinc(II) atoms. Other metal ions, such as Ca(II), Al(III), Ni(II), and Co(II), did not precipitate the BSA even when the metal ion to BSA ratios were in excess of 1000. The copper and zinc protein precipitates returned to solution after addition of the chelating agents, ethylenediaminetetraacetic acid (EDTA) or tetrathiometallates [(MS<inf>4</inf><sup>2 -</sup>), where M = Mo, W]. Two new choline and acetylcholine tetrathiomolybdate and tetrathiotungstate chelating agents have been synthesized and characterized. The infrared (IR) and X-ray crystal structures of the complexes revealed that the (MS<inf>4</inf><sup>2 -</sup>) cores had approximate T<inf>d</inf> symmetry in the choline (Ch) salts and C<inf>2v</inf> symmetry in the acetylcholine (AcCh) salts. The AcCh salts hydrolyzed more slowly than the ammonium or Ch salts and the tetrathiotungstate salts hydrolyzed approximately two orders of magnitude more slowly than the tetrathiomolybdate salts. The slower hydrolysis of tetrathiotungstate may make it more useful as an inorganic reagent and therapeutic agent. © 2007 Elsevier Inc. All rights reserved.",Cu binding;Disease;Mo;Protein precipitates;w;Zn binding;Alzheimer disease;angiogenesis;article;chelation;chemical structure;hydrolysis;Menkes syndrome;neurologic disease;precipitation;prion disease;synthesis;Wilson disease;acetylcholine;aluminum;ammonium derivative;bovine serum albumin;calcium;chelating agent;cholinate tetramolybdate;cholinate tetrathiotungstate;choline;cobalt;copper ion;edetic acid;metal ion;molybdenum;nickel;tungsten;unclassified drug;zinc,"Lee, V. E.;Schulman, J. M.;Stiefel, E. I.;Lee, C. C.",2007,November,http://dx.doi.org/10.1016/j.jinorgbio.2007.07.015,0,0,
2012,Peripheral neuropathy and inborn errors of metabolism in adults,"Although they are classically viewed as paediatric diseases, it is now recognized that inborn errors of metabolism (IEMs) can present at any age from childhood to adulthood. IEMs can involve the peripheral nervous system, mostly as part of a more diffuse neurological or systemic clinical picture. However, in some cases, the neuropathy can be the unique initial sign. Here, based on our personal experience and on a comprehensive literature analysis, we review IEMs causing neuropathies in adults. Diseases were classified according to the predominant type of neuropathies into (1) acute neuropathies, (2) mononeuropathy multiplex, (3) chronic axonal polyneuropathies, (4) chronic demyelinating polyneuropathies, (5) small-fibre neuropathies, and (6) lower motor neuron disease. © SSIEM and Springer 2007.",acute disease;adrenoleukodystrophy/di [Diagnosis];adrenoleukodystrophy/dt [Drug Therapy];adult;alpha tocopherol deficiency/dt [Drug Therapy];biotinidase deficiency/dt [Drug Therapy];cerebrotendinous xanthomatosis/di [Diagnosis];cerebrotendinous xanthomatosis/dt [Drug Therapy];congenital disorder of glycosylation/di [Diagnosis];demyelination/di [Diagnosis];demyelination/et [Etiology];disease classification;enzyme replacement;Fabry disease;globoid cell leukodystrophy/th [Therapy];GM2 gangliosidosis/dt [Drug Therapy];human;inborn error of metabolism/di [Diagnosis];metachromatic leukodystrophy/th [Therapy];mononeuropathy multiplex/di [Diagnosis];mononeuropathy multiplex/et [Etiology];motor neuron disease/di [Diagnosis];neuropathy/di [Diagnosis];neuropathy/et [Etiology];peripheral neuropathy/di [Diagnosis];peripheral neuropathy/et [Etiology];polyneuropathy/di [Diagnosis];polyneuropathy/et [Etiology];porphyria/di [Diagnosis];porphyria/th [Therapy];Refsum disease/di [Diagnosis];Refsum disease/th [Therapy];review;Tangier disease/di [Diagnosis];Tangier disease/dt [Drug Therapy];Tangier disease/th [Therapy];tyrosinemia/di [Diagnosis];tyrosinemia/th [Therapy];Wilson disease/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];antilipemic agent/dt [Drug Therapy];betaine;biotin/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];creatine;cyanocobalamin;folic acid;hydroxocobalamin;Lorenzo oil/dt [Drug Therapy];miglustat/dt [Drug Therapy];ornithine;penicillamine/dt [Drug Therapy];proline;pyridoxine;serine;zinc sulfate/dt [Drug Therapy],"Sedel, F.;Barnerias, C.;Dubourg, O.;Desguerres, I.;Lyon-Caen, O.;Saudubray, J. M.",2007,October,http://dx.doi.org/10.1007/s10545-007-0684-x,0,0,
2013,Different neurological outcome of liver transplantation for Wilson's disease in two homozygotic twins,"Wilson's disease is a genetic disorder characterized by accumulation of copper in many organs and tissues. Phenotypic manifestations are wide-ranging from neuropsychiatric disorders, to severe liver disease requiring liver transplantation. Clinical presentation is not often related to the genetic defect and siblings may have different type of disease. Liver transplantation is indicated for all patients with Wilson's disease and decompensated liver cirrhosis unresponsive to medical therapy, but its efficacy in resolving the neurological symptoms is still controversial, because as far now, very different outcomes have been reported. We describe here on the exceptional case of two homozygotic twins, both with liver cirrhosis due to Wilson's disease, one of them with severe neuropsychiatric involvement, who both underwent liver transplantation and subsequently had very different outcome despite same genetic background. The presence of neurological clinical manifestations in Wilson's disease should recommend caution indicating liver transplantation, because irreversible brain damage may exist. © 2006 Elsevier B.V. All rights reserved.",Homozygotic twins;Liver disease;Liver transplantation;Neurological disease;Wilson's disease;adult;article;ataxia/dt [Drug Therapy];brain damage;case report;chemical analysis;clinical feature;dysmetria/dt [Drug Therapy];genetics;human;human tissue;limb weakness/dt [Drug Therapy];liver cirrhosis/co [Complication];liver cirrhosis/su [Surgery];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver histology;male;mental disease/dt [Drug Therapy];monozygotic twins;neuropsychiatry;psychopathy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];lorazepam/dt [Drug Therapy];orphenadrine/dt [Drug Therapy];perphenazine/dt [Drug Therapy];pimozide/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Senzolo, M.;Loreno, M.;Fagiuoli, S.;Zanus, G.;Canova, D.;Masier, A.;Russo, F. P.;Sturniolo, G. C.;Burra, P.",2007,January,http://dx.doi.org/10.1016/j.clineuro.2006.01.008,0,0,
2014,Antitumor and antiinflammatory effects of tetrathiotungstate in comparison with tetrathiomolybdate,"Tetrathiomolybdate (TM) is an anticopper drug under development for treating Wilson's disease. Its mechanism of action involves forming a tight tripartite complex in the blood with serum albumin and available copper. When available copper levels are lowered in animals with TM, strong antiangiogenic and antitumor effects are observed. Similarly, TM has excellent efficacy in animal models of fibrotic, inflammatory, and autoimmune diseases, and it protects against heart damage from doxorubicin (DXR) and liver damage from acetaminophen, carbon tetrachloride, and concanavalin A. Tetrathiotungstate (TT) also forms a similar tripartite complex in the blood and has similar effects to TM on copper. In this article, whether TT had similar antitumor effects, and similar effects in protecting the heart against DXR toxicity, as TM was evaluated. It was found that the 2 drugs were comparable in their effects when doses were used that lowered copper availability to the same extent. © 2007 Mosby, Inc. All rights reserved.",animal cell;animal experiment;antiinflammatory activity;antineoplastic activity;article;drug bioavailability;heart protection;mouse;nonhuman;priority journal;antiinflammatory agent;antineoplastic agent;copper;doxorubicin;tetrathiomolybdic acid/cm [Drug Comparison];tetrathiotungstic acid/cm [Drug Comparison];tetrathiotungstic acid/po [Oral Drug Administration];unclassified drug,"Hou, G.;Dick, R.;Zeng, C.;Brewer, G. J.",2007,May,http://dx.doi.org/10.1016/j.trsl.2006.12.003,0,0,
2015,"The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury","Mercury has been a known as a toxic substance for centuries. Whilst the clinical features of acute mercury poisoning have been well described, chronic low dose exposure to mercury remains poorly characterised and its potential role in various chronic disease states remains controversial. Low molecular weight thiols, i.e. sulfhydryl containing molecules such as cysteine, are emerging as important factors in the transport and distribution of mercury throughout the body due to the phenomenon of ""Molecular Mimicry"" and its role in the molecular transport of mercury. Chelation agents such as the dithiols sodium 2,3-dimercaptopropanesulfate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are the treatments of choice for mercury toxicity. Alpha-lipoic acid (ALA), a disulfide, and its metabolite dihydrolipoic acid (DHLA), a dithiol, have also been shown to have chelation properties when used in an appropriate manner. Whilst N-acetyl-cysteine (NAC) and glutathione (GSH) have been recommended in the treatment of mercury toxicity in the past, an examination of available evidence suggests these agents may in fact be counterproductive. Zinc and selenium have also been shown to exert protective effects against mercury toxicity, most likely mediated by induction of the metal binding proteins metallothionein and selenoprotein-P. Evidence suggests however that the co-administration of selenium and dithiol chelation agents during treatment may also be counter-productive. Finally, the issue of diagnostic testing for chronic, historical or low dose mercury poisoning is considered including an analysis of the influence of ligand interactions and nutritional factors upon the accuracy of ""chelation challenge"" tests. © 2007 Elsevier Ireland Ltd. All rights reserved.",dmps;dmsa;Fibre;Lipoic acid;Mercury;Thiols;accuracy;analytic method;arsenic poisoning/dt [Drug Therapy];blood brain barrier;blood level;cadmium poisoning/dt [Drug Therapy];chelation;detoxification;diagnostic test;dietary fiber;drug half life;flu like syndrome/si [Side Effect];gastrointestinal disease/si [Side Effect];half life time;human;ingestion;kidney disease/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];low drug dose;mercurialism/si [Side Effect];mercurialism/dt [Drug Therapy];neutropenia/si [Side Effect];nonhuman;nutrition;occupational exposure;priority journal;rash/si [Side Effect];review;transport kinetics;unspecified side effect/si [Side Effect];urine level;Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];acetylcysteine/po [Oral Drug Administration];acetylcysteine/pd [Pharmacology];chelating agent/dt [Drug Therapy];dihydrolipoate;dithiol derivative;ethylmercuric chloride/to [Drug Toxicity];ethylmercury derivative/to [Drug Toxicity];glutathione/dt [Drug Therapy];ligand;mercury/to [Drug Toxicity];metallothionein;methylmercuric chloride/to [Drug Toxicity];methylmercury/to [Drug Toxicity];selenium/dt [Drug Therapy];selenium/pd [Pharmacology];selenomethionine/cm [Drug Comparison];selenomethionine/dt [Drug Therapy];selenomethionine/pd [Pharmacology];selenoprotein P;sodium selenite/cm [Drug Comparison];sodium selenite/dt [Drug Therapy];sodium selenite/pd [Pharmacology];succimer/ae [Adverse Drug Reaction];succimer/dt [Drug Therapy];succimer/po [Oral Drug Administration];succimer/pk [Pharmacokinetics];succimer/pd [Pharmacology];thioctic acid/ae [Adverse Drug Reaction];thioctic acid/cr [Drug Concentration];thioctic acid/do [Drug Dose];thioctic acid/dt [Drug Therapy];thioctic acid/pk [Pharmacokinetics];thiol derivative;unithiol/ae [Adverse Drug Reaction];unithiol/dt [Drug Therapy];unithiol/iv [Intravenous Drug Administration];unithiol/po [Oral Drug Administration];unithiol/pk [Pharmacokinetics];zinc/dt [Drug Therapy],"Rooney, J. P. K.",2007,20 May,http://dx.doi.org/10.1016/j.tox.2007.02.016,0,0,
2016,"Early and severe liver disease associated with homozygosity for an exon 7 mutation, G691R, in Wilson's disease [2]",,adolescent;amino acid substitution;child;clinical article;clinical evaluation;clinical feature;consanguineous marriage;diet therapy;disease severity;DNA extraction;DNA sequence;early diagnosis;exon;gene amplification;genetic analysis;genetic screening;genotype phenotype correlation;hepatitis;homozygosity;human;Lebanon;letter;liver cirrhosis;liver disease;missense mutation;onset age;pedigree analysis;polymerase chain reaction;priority journal;sequence analysis;single nucleotide polymorphism;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];arginine/ec [Endogenous Compound];copper/ec [Endogenous Compound];DNA/ec [Endogenous Compound];glycine/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Barada, K.;Nemer, G.;Elhajj, I. I.;Touma, J.;Cortas, N.;Boustany, R. M.;Usta, J.",2007,September,http://dx.doi.org/10.1111/j.1399-0004.2007.00853.x,0,0,
2017,D-penicillamine. [Spanish],,agranulocytosis/si [Side Effect];allergic reaction/si [Side Effect];arthralgia/si [Side Effect];autoimmune disease;autoimmune thyroiditis/si [Side Effect];biliary cirrhosis;breast milk;bronchiolitis obliterans;bronchus obstruction/si [Side Effect];cataract/si [Side Effect];clinical practice;concentration loss;cystitis/si [Side Effect];dermatitis/si [Side Effect];diplopia/si [Side Effect];drug absorption;drug hypersensitivity/si [Side Effect];drug indication;drug solubility;drug structure;edema/si [Side Effect];elastosis/si [Side Effect];erythema/si [Side Effect];fever;fibrosis;gastrointestinal disease;gastrointestinal symptom/si [Side Effect];gynecomastia/si [Side Effect];hematuria/si [Side Effect];hemolytic anemia/si [Side Effect];human;hypertrichosis/si [Side Effect];immunoglobulin deficiency/si [Side Effect];immunology;intoxication;lactation;leukopenia/si [Side Effect];liver failure;liver hemosiderosis/si [Side Effect];liver metabolism;liver toxicity/si [Side Effect];lupus erythematosus;lymphadenopathy/si [Side Effect];micturition;migraine;myasthenia gravis/si [Side Effect];necrotizing arteritis;nephrotoxicity/si [Side Effect];optic neuritis/si [Side Effect];papular rash/si [Side Effect];pemphigoid/si [Side Effect];pharmacogenetics;pharynx disease/si [Side Effect];photophobia/si [Side Effect];polycythemia/si [Side Effect];polymyositis/si [Side Effect];prematurity;primary sclerosing cholangitis;proteinuria/si [Side Effect];psoriasis;psychiatry;rash/si [Side Effect];retinitis/si [Side Effect];retinopathy;rheumatoid arthritis;short survey;side effect/si [Side Effect];Sjoegren syndrome/si [Side Effect];skin disease;stomatitis/si [Side Effect];survival;systemic lupus erythematosus/si [Side Effect];third trimester pregnancy;thrombocytopenia/si [Side Effect];thrombocytosis/si [Side Effect];treatment indication;urticaria/si [Side Effect];vasculitis/si [Side Effect];weight gain;Wilson disease/dt [Drug Therapy];antacid agent;cadmium;copper;digoxin;glucose 6 phosphate dehydrogenase/ec [Endogenous Compound];isoniazid;macroglobulin/ec [Endogenous Compound];mercury;penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pk [Pharmacokinetics];protein/ec [Endogenous Compound];zinc,Anonymous,2007,August,http://dx.doi.org/10.1016/S1578-1550%2807%2975675-9,0,0,
2018,Wilson's disease: What lies beneath [2],,Abnormal liver function tests;Ceruloplasmin;Copper quantification;Liver biopsy;Trientine;adult;anamnesis;case report;deterioration;fatty liver/di [Diagnosis];female;hepatitis B/dt [Drug Therapy];hepatitis B/et [Etiology];Hepatitis B virus;human;laboratory test;letter;liver cirrhosis/di [Diagnosis];liver function test;patient referral;priority journal;Viet Nam;virus load;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adefovir dipivoxil/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];trientine/dt [Drug Therapy];virus DNA,"Morra, H. A. L.;Debes, J. D.;Dickstein, G.",2007,April,http://dx.doi.org/10.1007/s10620-006-9463-z,0,0,
2019,Conjugated hyperbilirubinemia: Screening and treatment in older infants and children,,Alagille syndrome;alpha 1 antitrypsin deficiency/di [Diagnosis];bile duct atresia;bilirubin metabolism;differential diagnosis;echography;human;hyperbilirubinemia;jaundice;laboratory test;liver biopsy;liver transplantation;newborn hepatitis;obstructive jaundice/di [Diagnosis];periodic acid Schiff stain;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];bilirubin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Harb, R.;Thomas, D. W.",2007,March,http://dx.doi.org/10.1542/pir.28-3-83,0,0,
2020,Successful treatment of tremor in Wilson's disease by thalamotomy: A case report,"Little information is available on the surgical treatment of movement disorders in Wilson's disease. We report a successful outcome of left-sided stereotactic thalamotomy in a 30-year-old man with Wilson's disease, who had severe postural-kinetic tremor of both hands. The improvement was bilateral. Our case illustrates that stereotactic thalamotomy may be considered as an option in treating severe tremor in selected patients of Wilson's disease and merit further trials. © 2007 Movement Disorder Society.",Thalamotomy;Tremor;Wilson's disease;adult;anamnesis;article;case report;clinical feature;copper blood level;disease course;disease severity;follow up;hand movement;human;laboratory test;male;motor dysfunction/di [Diagnosis];motor dysfunction/dt [Drug Therapy];motor dysfunction/su [Surgery];neuropsychological test;nuclear magnetic resonance imaging;outcome assessment;patient attitude;patient compliance;physical examination;priority journal;surgical technique;symptom;treatment outcome;tremor/di [Diagnosis];tremor/dt [Drug Therapy];tremor/su [Surgery];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];clonazepam/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];primidone/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Pal, P. K.;Sinha, S.;Pillai, S.;Taly, A. B.;Abraham, R. G.",2007,15 Nov,http://dx.doi.org/10.1002/mds.21750,0,0,
2021,Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation,"Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b)] is a transcription factor implicated in the genesis of Mowat-Wilson syndrome in humans. Sip1 expression in the dorsal telencephalon of mouse embryos was documented from E12.5. We inactivated the gene specifically in cortical precursors. This resulted in the lack of the entire hippocampal formation. Sip1 mutant mice exhibited death of differentiating cells and decreased proliferation in the region of the prospective hippocampus and dentate gyrus. The expression of the Wnt antagonist Sfrp1 was ectopically activated, whereas the activity of the noncanonical Wnt effector, JNK, was down-regulated in the embryonic hippocampus of mutant mice. In cortical cells, Sip1 protein was detected on the promoter of Sfrp1 gene and both genes showed a mutually exclusive pattern of expression suggesting that Sfrp1 expression is negatively regulated by Sip1. Sip1 is therefore essential to the development of the hippocampus and dentate gyrus, and is able to modulate Wnt signaling in these regions. © 2007 by The National Academy of Sciences of the USA.",Cortex;Development;Knockout;sfrp1;Telencephalon;animal experiment;animal tissue;article;brain development;brain malformation/cn [Congenital Disorder];cell proliferation;controlled study;dentate gyrus;embryo development;gene;gene expression regulation;gene inactivation;hippocampus;mouse;mowat wilson syndrome/cn [Congenital Disorder];nerve cell necrosis;nonhuman;priority journal;promoter region;protein expression;sFrp1 gene;signal transduction;sip1 gene;smad interacting protein 1/ec [Endogenous Compound];stress activated protein kinase/ec [Endogenous Compound];transcription factor/ec [Endogenous Compound];unclassified drug;Wnt protein/ec [Endogenous Compound],"Miquelajauregui, A.;Van De Putte, T.;Polyakov, A.;Nityanandam, A.;Boppana, S.;Seuntjens, E.;Karabinos, A.;Higashi, Y.;Huylebroeck, D.;Tarabykin, V.",2007,31 Jul,http://dx.doi.org/10.1073/pnas.0609863104,0,0,
2022,Unified Wilson's Disease Rating Scale - A proposal for the neurological scoring of Wilson's disease patients,"Background and purpose: The clinical forms of Wilson's disease (WD) neurological manifestations can be divided into three movement disorder syndromes: a) dystonic, b) ataxic, c) parkinsonian syndrome. These syndromes in WD seldom occur in isolation. Clinical rating scales such as the Unified Parkinson's Disease Rating Scale (UPDRS), the International Cooperative Ataxia Rating Scale (ICARS) and the Rating Scale for Dystonia (RSD), focusing on either parkinsonism or ataxia or dystonia alone, are not sufficient to reflect accurately the motor impairment of WD patients. The aim of the study was to develop a novel rating scale for WD, because as far as we know no scale for the clinical rating in WD has been designed before. Material and methods: In 2004 the EuroWilson consortium was founded, to create a European WD database. Members of the consortium from Poland, Germany, and France prepared a new scale using clinical rating scales as the UPDRS, ICARS, and RSD. Prepared drafts were discussed several times in detail at the first international neurological EuroWilson meeting in September 2004 in Paris and in November in Warsaw. Results and conclusions: The novel scale for WD consists of 3 parts, including: Consciousness, a historical review based on the Barthel scale (2-11 items), and neurological examination (12-35, items). The maximum score for the first part is 3, for the second 39 points, and for the last 143 points. The initial reliability of the scale on the basis of 6 patients (on DVD) and 8 investigators was assessed. Inter-rater agreement was high. Now the scale is used by the EuroWilson and GeNeMove consortia.",Neurological scoring;Unified Wilson's Disease Scale;Wilson's disease;adult;article;ataxia;Barthel index;ceruloplasmin blood level;clinical article;consciousness level;copper blood level;data base;dystonia;Europe;female;France;Germany;human;interrater reliability;male;neurologic examination;patient assessment;Poland;rating scale;Unified Parkinson Disease Rating Scale;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Czlonkowska, A.;Tarnacka, B.;Moller, J. C.;Leinweber, B.;Bandmann, O.;Woimant, F.;Oertel, W. H.",2007,,,0,0,
2023,Molecular determinants of Alzheimer's disease Abeta peptide neurotoxicity,"The Alzheimer's disease amyloid precursor protein is sequentially processed to yield the neurotoxic amyloid-beta (Abeta) peptide, which is the principal component of the senile plaques in Alzheimer's disease brains. This review will outline the current thinking on how Abeta mediates neurotoxicity or neuronal dysfunction. In particular, this article will focus on the key residues that modulate Abeta's activity and the cellular pathways and mechanisms involved. It will detail how Abeta-metal interactions are a key determinate in Alzheimer's disease pathogenesis. © 2007 Future Medicine Ltd.","Abeta;Alzheimer's disease;Amyloid;Metal;Neurodegeneration;Oligomer;Oxidative stress;Synapse;Tau;Toxicity;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];blood brain barrier;cell death;clinical trial;cross linking;human;long term potentiation;metal binding;nerve degeneration;neuropathology;neuroprotection;neurotoxicity;nonhuman;oxidation reduction reaction;priority journal;protein interaction;review;Wilson disease/dt [Drug Therapy];1,1' xylylbis(1,4,8,11 tetraazacyclotetradecane);alpha secretase/ec [Endogenous Compound];alpha tocopherol/ct [Clinical Trial];alpha tocopherol/cb [Drug Combination];alpha tocopherol/dt [Drug Therapy];amyloid beta protein/ec [Endogenous Compound];amyloid beta protein[1-42]/ec [Endogenous Compound];amyloid precursor protein/ec [Endogenous Compound];antioxidant/ct [Clinical Trial];antioxidant/dt [Drug Therapy];antioxidant/pd [Pharmacology];ascorbic acid/ct [Clinical Trial];ascorbic acid/cb [Drug Combination];ascorbic acid/dt [Drug Therapy];beta secretase/ec [Endogenous Compound];chelating agent;clioquinol/ct [Clinical Trial];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];copper ion/ec [Endogenous Compound];curcumin/pd [Pharmacology];cyclam derivative;dp 109;Ginkgo biloba extract/pd [Pharmacology];gossypine/pd [Pharmacology];jkl 169;melatonin/pd [Pharmacology];n methyl dextro aspartic acid receptor/ec [Endogenous Compound];placebo;trientine/dt [Drug Therapy];unclassified drug;zinc/ec [Endogenous Compound]","Cappai, R.;Barnham, K. J.",2007,July,http://dx.doi.org/10.2217/14796708.2.4.397,0,0,
2024,Treatment of dystonia,"Numerous therapies are potentially useful in the management of patients with dystonia. In this chapter, the available therapeutic options are reviewed, including modalities that have entered the clinician's armamentarium relatively recently, with emphasis on the selection of an approach tailored to the individual patient's specific considerations. © 2007 Lippincott Williams & Wilkins, Inc.",akathisia/si [Side Effect];ataxia/si [Side Effect];blurred vision/si [Side Effect];brain depth stimulation;cardiovascular disease/si [Side Effect];clinical trial;confusion/si [Side Effect];constipation/si [Side Effect];depression/si [Side Effect];drug dose increase;drug megadose;dystonia/dt [Drug Therapy];dystonia/su [Surgery];dystonia/th [Therapy];human;hypotension/si [Side Effect];irritability;low drug dose;nausea/si [Side Effect];nonhuman;occupational therapy;paresthesia/si [Side Effect];parkinsonism/si [Side Effect];physiotherapy;respiration depression/si [Side Effect];review;sedation;side effect/si [Side Effect];surgical technique;treatment response;urinary urgency/si [Side Effect];urine retention/si [Side Effect];Wilson disease/dt [Drug Therapy];xerostomia/si [Side Effect];baclofen/ae [Adverse Drug Reaction];baclofen/dt [Drug Therapy];baclofen/tl [Intrathecal Drug Administration];baclofen/po [Oral Drug Administration];benzatropine mesilate/dt [Drug Therapy];benzatropine mesilate/po [Oral Drug Administration];botulinum toxin/dt [Drug Therapy];botulinum toxin A/ct [Clinical Trial];botulinum toxin A/dt [Drug Therapy];botulinum toxin B/ct [Clinical Trial];botulinum toxin B/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];carbidopa plus levodopa/po [Oral Drug Administration];cholinergic receptor blocking agent/ae [Adverse Drug Reaction];cholinergic receptor blocking agent/dt [Drug Therapy];clonazepam/ae [Adverse Drug Reaction];clonazepam/dt [Drug Therapy];clonazepam/po [Oral Drug Administration];clozapine/ct [Clinical Trial];clozapine/dt [Drug Therapy];diazepam/dt [Drug Therapy];diazepam/po [Oral Drug Administration];diphenhydramine/dt [Drug Therapy];diphenhydramine/iv [Intravenous Drug Administration];diphenhydramine/po [Oral Drug Administration];levodopa/ct [Clinical Trial];levodopa/dt [Drug Therapy];lithium/ct [Clinical Trial];lithium/dt [Drug Therapy];lorazepam/dt [Drug Therapy];lorazepam/po [Oral Drug Administration];olanzapine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];perphenazine/dt [Drug Therapy];pimozide/cb [Drug Combination];pimozide/dt [Drug Therapy];profenamine/dt [Drug Therapy];profenamine/po [Oral Drug Administration];quetiapine/dt [Drug Therapy];reserpine/ae [Adverse Drug Reaction];reserpine/dt [Drug Therapy];risperidone/dt [Drug Therapy];tetrabenazine/ae [Adverse Drug Reaction];tetrabenazine/ct [Clinical Trial];tetrabenazine/cb [Drug Combination];tetrabenazine/dt [Drug Therapy];tetrabenazine/po [Oral Drug Administration];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];trihexyphenidyl/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];trihexyphenidyl/po [Oral Drug Administration];unindexed drug;valproic acid/ct [Clinical Trial];valproic acid/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Geyer, H. L.;Bressman, S. B.",2007,February,,0,0,
2025,Wilson's disease. [German],"Wilson's disease is a rare autosomal recessive disorder of hepatic copper transport leading to a biliary excretion inhibition of copper. Overload of the metal mainly in liver and basal ganglia leads to hepatic but also to extrapyramidal motor as well as psychiatric clinical symptoms. Diagnosis is based on clinical suspicion, parameters of copper metabolism, ophthalmic examination and a liver biopsy. A radiocoppertest is able to identify patients even with inconsistent laboratory results. For initial assessment and follow-up neurophysiological investigation and MRI are recommended additionally. Genetic analysis can be helpful to detect asymptomatic relatives of the index patient. Dependent on the stage of the disease for therapy chelating drugs and zinc are possible but must be given lifelong without longer interruptions. With early diagnosis and consequent treatment the prognosis of Wilson's disease is excellent and usually the need for liver transplantation can be prevented. © 2007 by Verlag Hans Huber, Hogrefe AG.",biliary excretion;copper metabolism;diagnostic test;electroneurology;extrapyramidal syndrome;follow up;gene mutation;genetic analysis;human;liver biopsy;liver transplantation;mental disease;pathogenesis;radiation detection;review;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper;penicillamine/dt [Drug Therapy];trientine,"Gunther, P.;Hermann, W.;Kuhn, H. J.;Wagner, A.",2007,January,http://dx.doi.org/10.1024/0040-5930.64.1.57,0,0,
2026,Diagnosis and long-term management of Wilson disease,,ATP7B gene;basal ganglion;copper metabolism;gene;human;liver failure/co [Complication];liver graft;note;prothrombin time;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/pd [Pharmacology],"Schilsky, M. L.",2007,January,,0,0,
2027,Treatment of tremor,"Tremor, a rhythmic and oscillatory movement, is commonly encountered in clinical practice. The focus of this chapter is the treatment of nonparkinsonian tremors. While the most common of these tremor disorders is essential tremor, the treatment of other disorders (eg, dystonic tremor, cerebellar tremor, orthostatic tremor) is discussed as well. The treatment of a given tremor disorder involves the use of selected medications and, in the setting of severe, medically refractory movements, the use of surgery. © 2007 Lippincott Williams & Wilkins, Inc.",action tremor/dt [Drug Therapy];ataxia/si [Side Effect];bradycardia/si [Side Effect];brain hemorrhage/co [Complication];cerebellum tremor/dt [Drug Therapy];clinical trial;confusion/si [Side Effect];depression/si [Side Effect];disease association;drowsiness/si [Side Effect];drug dose increase;drug dose titration;dysphagia/si [Side Effect];essential tremor/dt [Drug Therapy];fatigue/si [Side Effect];feedback system;hemiparesis/co [Complication];Holmes tremor/dt [Drug Therapy];human;impotence/si [Side Effect];low drug dose;memory disorder/si [Side Effect];micturition disorder/si [Side Effect];nausea/si [Side Effect];orthostatic tremor/dt [Drug Therapy];paresthesia/si [Side Effect];peripheral neuropathy/dt [Drug Therapy];psychogenic tremor/dt [Drug Therapy];review;side effect/si [Side Effect];somnolence/si [Side Effect];surgical mortality;thalamotomy;tremor/dt [Drug Therapy];tremor/si [Side Effect];tremor/su [Surgery];vomiting/si [Side Effect];weight reduction;Wilson disease/dt [Drug Therapy];acetazolamide/dt [Drug Therapy];alprazolam/dt [Drug Therapy];amiodarone/ae [Adverse Drug Reaction];baclofen/ae [Adverse Drug Reaction];baclofen/dt [Drug Therapy];baclofen/po [Oral Drug Administration];botulinum toxin/ae [Adverse Drug Reaction];botulinum toxin/dt [Drug Therapy];botulinum toxin/im [Intramuscular Drug Administration];buspirone/ct [Clinical Trial];buspirone/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];clonazepam/dt [Drug Therapy];diazepam/dt [Drug Therapy];ethosuximide/dt [Drug Therapy];etiracetam/dt [Drug Therapy];gabapentin/ct [Clinical Trial];gabapentin/dt [Drug Therapy];interferon/ae [Adverse Drug Reaction];isoniazid/ct [Clinical Trial];isoniazid/dt [Drug Therapy];lithium/ae [Adverse Drug Reaction];lorazepam/dt [Drug Therapy];metoprolol/dt [Drug Therapy];octanol/ct [Clinical Trial];octanol/dt [Drug Therapy];oxybate sodium/ct [Clinical Trial];oxybate sodium/dt [Drug Therapy];phenytoin/dt [Drug Therapy];primidone/ae [Adverse Drug Reaction];primidone/ct [Clinical Trial];primidone/cb [Drug Combination];primidone/cm [Drug Comparison];primidone/dt [Drug Therapy];propranolol/ae [Adverse Drug Reaction];propranolol/ct [Clinical Trial];propranolol/cb [Drug Combination];propranolol/cm [Drug Comparison];propranolol/dt [Drug Therapy];sotalol/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];topiramate/ae [Adverse Drug Reaction];topiramate/ct [Clinical Trial];topiramate/dt [Drug Therapy];trientine/dt [Drug Therapy];trihexyphenidyl/ae [Adverse Drug Reaction];trihexyphenidyl/dt [Drug Therapy];unindexed drug;zinc/dt [Drug Therapy],"Louis, E. D.",2007,February,,0,0,
2028,Wilson's disease: clinical study and molecular biology. [French],"Wilson disease is an autosomal recessive disorder of copper transport that causes hepatic and/or neurological disease resulting from copper accumulation in the liver and brain. The protein defective in this disorder is a putative copper-transporting P-type ATPase, ATP7B. More than 300 mutations have been identified in the ATP7B gene of patients with Wilson disease. This work reported an observation of a case of Wilson disease in young girl a ten-years-old born of a consanguineous marriage of the first degree. This young girl was hospitalized on 4 January 2003 in paediatric of the child hospital, CHU Ibn Rochd of Casablanca for a syndrome oedemato-ascitic with collateral circulation. Biological investigation and the sequencing of all exons of ATP7B gene were carried out. We have noted a hypoceruloplasminemy (0.03 g/l), a cupremy (18 mug/100 ml) and a high cuprurie (356 mug/24 h). The sequencing of the 21 exons ATP7B gene showed the absence of the mutations. © 2007 Elsevier Masson SAS. All rights reserved.",atp7b;Copper;Wilson disease;abdominal distension;alanine aminotransferase blood level;article;ascites;aspartate aminotransferase blood level;case report;collateral circulation;consanguineous marriage;drug dose reduction;drug withdrawal;edema;epistaxis;exon;female;gene mutation;gene sequence;hematuria;hospitalization;human;human tissue;iron deficiency anemia;liver biopsy;priority journal;rectum hemorrhage;school child;thrombocytopenia;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];spironolactone/dt [Drug Therapy],"Dhidah, K.;El Filali, F.;Naamane, A.;Hadj Khalifa, H.;Aquaron, R.",2007,December,http://dx.doi.org/10.1016/j.immbio.2007.09.006,0,0,
2029,Epilepsy and inborn errors of metabolism in adults: A diagnostic approach,"Inborn errors of metabolism (IEMs) represent poorly known causes of epilepsy in adulthood. Although rare, these are important to recognize for several reasons: some IEMs respond to specific treatments, some antiepileptic drugs interfering with metabolic pathways may worsen the clinical condition, and specific genetic counselling can be provided. We review IEMs potentially revealed by epilepsy that can be encountered in an adult neurology department. We distinguished progressive myoclonic epilepsies (observed in some lysosomal storage diseases, respiratory chain disorders and Lafora disease), from other forms of epilepsies (observed in disorders of intermediary metabolism, including porphyrias, creatine metabolism defects, glucose transporter (GLUT-1) deficiency, Wilson disease or succinic semialdehyde dehydrogenase deficiency). We propose a diagnostic approach and point out clinical, radiological and electrophysiological features that suggest an IEM in an epileptic patient. © SSIEM and Springer 2007.",adult;blood analysis;cerebrospinal fluid examination;clinical feature;diagnostic value;dialysis;disorders of mitochondrial functions/di [Diagnosis];drug choice;drug contraindication;drug efficacy;drug megadose;drug response;drug safety;electroencephalography;enzyme deficiency/di [Diagnosis];enzyme deficiency/dt [Drug Therapy];enzyme deficiency/et [Etiology];enzyme therapy;epilepsy/di [Diagnosis];epilepsy/dt [Drug Therapy];epilepsy/et [Etiology];epilepsy/si [Side Effect];Gaucher disease/di [Diagnosis];Gaucher disease/dt [Drug Therapy];gene mutation;genetic counseling;genetic risk;genetic screening;histopathology;human;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/dt [Drug Therapy];inborn error of metabolism/et [Etiology];inborn error of metabolism/th [Therapy];ketogenic diet;lipofuscinosis/di [Diagnosis];lipofuscinosis/dt [Drug Therapy];lipofuscinosis/et [Etiology];lysosome storage disease/di [Diagnosis];mental deficiency;metabolic disorder/si [Side Effect];myoclonus epilepsy/di [Diagnosis];myoclonus epilepsy/dt [Drug Therapy];myoclonus epilepsy/et [Etiology];nervous system electrophysiology;nuclear magnetic resonance imaging;onset age;porphyria/di [Diagnosis];protein deficiency/di [Diagnosis];protein restriction;respiratory tract disease/di [Diagnosis];review;risk assessment;seizure/si [Side Effect];sialidosis/di [Diagnosis];sialidosis/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];anticonvulsive agent/ae [Adverse Drug Reaction];anticonvulsive agent/dt [Drug Therapy];arginine/ec [Endogenous Compound];arylbutyric acid derivative/dt [Drug Therapy];benzodiazepine derivative/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];carbamazepine/ae [Adverse Drug Reaction];carbamazepine/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];creatine/ec [Endogenous Compound];diazepam/ae [Adverse Drug Reaction];diazepam/dt [Drug Therapy];etiracetam/dt [Drug Therapy];gabapentin/ae [Adverse Drug Reaction];gabapentin/dt [Drug Therapy];gene product/ec [Endogenous Compound];glucose transporter 1/ec [Endogenous Compound];guanine/ec [Endogenous Compound];lamotrigine/ae [Adverse Drug Reaction];lamotrigine/dt [Drug Therapy];mitochondrial DNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phenobarbital/ae [Adverse Drug Reaction];phenobarbital/dt [Drug Therapy];phenytoin/ae [Adverse Drug Reaction];phenytoin/dt [Drug Therapy];piracetam/dt [Drug Therapy];succinate semialdehyde dehydrogenase/ec [Endogenous Compound];theophylline;tiagabine/ae [Adverse Drug Reaction];tiagabine/dt [Drug Therapy];topiramate/ae [Adverse Drug Reaction];topiramate/dt [Drug Therapy];trientine/dt [Drug Therapy];unindexed drug;valproic acid/ae [Adverse Drug Reaction];valproic acid/dt [Drug Therapy];vigabatrin/ae [Adverse Drug Reaction];vigabatrin/dt [Drug Therapy];zinc/dt [Drug Therapy];zonisamide/dt [Drug Therapy],"Sedel, F.;Gourfinkel-An, I.;Lyon-Caen, O.;Baulac, M.;Saudubray, J. M.;Navarro, V.",2007,November,http://dx.doi.org/10.1007/s10545-007-0723-7,0,0,
2030,Polyneuropathy associated with Wilson's disease,,adult;article;case report;electromyography;electroneurography;electrophysiology;history of medicine;hospital admission;human;immunohistochemistry;laboratory test;liver biopsy;male;nerve conduction;nerve fiber degeneration;nerve potential;neurologic examination;nuclear magnetic resonance imaging;paresthesia;pathology;polyneuropathy/co [Complication];polyneuropathy/di [Diagnosis];polyneuropathy/et [Etiology];sensory nerve;treatment duration;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Yerdelen, D.;Koc, F.;Zorludemir, S.",2007,October,,0,0,
2031,Wilson's disease presenting as isolated obsessive-compulsive disorder,"Wilson's disease (WD) is a genetic neurodegenerative disorder; it exhibits wide heterogeneity in symptoms and usually presents with liver disease and/ or neuropsychiatric manifestations. The common neurological manifestations observed are dysarthria, gait disturbance, dystonia, rigidity, tremor, dysphagia and chorea. The frequent psychiatric manifestations reported are personality and mood changes, depression, phobias, cognitive impairment, psychosis, anxiety, compulsive and impulsive behavior. Isolated obsessive-compulsive disorder (OCD) is a rare presentation of WD. Reported herein is a case of a 17-year-old boy with isolated OCD. He presented to the psychiatrist with symptoms of contamination obsessions and washing compulsions, along with compulsion of repeated feet tapping, and was treated with adequate doses of fluoxetine for 6 months but did not improve. Later on, he was diagnosed as a case of WD and showed improvement with chelating and behavior therapy. This implies the importance of the occurrence of isolated psychological symptoms in WD.",Obsessive-compulsive disorder;Psychiatric manifestations;Wilson's disease;adolescent;article;behavior therapy;case report;chelation therapy;computer assisted tomography;drug dose increase;general aspects of disease;human;male;neurologic examination;obsessive compulsive disorder/di [Diagnosis];obsessive compulsive disorder/dt [Drug Therapy];rating scale;treatment duration;treatment outcome;Wilson disease;chelating agent/dt [Drug Therapy];fluoxetine/do [Drug Dose];fluoxetine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Kumawat, B.;Sharma, C.;Tripathi, G.;Ralot, T.;Dixit, S.",2007,01 Nov,,0,0,
2032,"A study on the concentrations of serum zinc, non-ceruloplasmin copper, reactive oxygen and nitrogen species in children with Wilson's disease",,adolescent;blood analysis;blood chemistry;child;clinical article;controlled study;copper blood level;human;letter;oxidative stress;priority journal;Wilson disease;zinc blood level;copper/ec [Endogenous Compound];reactive nitrogen species/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Geetha, A.;Jeyachristy, S. A.;Selvamathy, S. M. K. N.;Ilavarasi, S.;Surendran, R.",2007,August,http://dx.doi.org/10.1016/j.cca.2007.05.005,0,0,
2033,Late manifestation of Wilson's disease: A case report. [Czech],"A case of a woman examined repeatedly at different medical workplaces because of a progressive tremor of the head is presented. This symptom started at the patient's age of 55 years. The investigations have not revealed etiology of the clinical state so far. Previous therapy was also ineffective. The patient was sent for an examination to our department seven years after the symptoms had appeared. The liver biopsy showed an increased copper amount in the liver, and that led to the diagnosis of Wilson's disease. The symptoms of the disease were atypical and occurred late. This case-report has confirmed possibility of a rare occurrence of this disease in elderly patients with dyskinesia without clear etiology.",Ceruloplasmin;Liver biopsy;Magnetic resonance;Tremor;Wilson's disease;adult;article;case report;clinical feature;disease activity;female;human;nuclear magnetic resonance imaging;single photon emission computer tomography;symptomatology;tremor/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];clonazepam/dt [Drug Therapy];copper;levodopa/dt [Drug Therapy];penicillamine/dt [Drug Therapy];plasmin/ec [Endogenous Compound];primidone/dt [Drug Therapy],"Valis, M.;Talab, R.;Bartova, J.;Hulek, P.;Zizka, J.;Masopust, J.",2007,,,0,0,
2034,Revised King's College score for liver transplantation in adult patients with Wilson's disease,"Fulminant Wilson's disease (WD) is almost invariably fatal, and liver transplantation is the only life-saving treatment. Decompensated chronic WD usually responds to chelation therapy. Our aim was to validate 3 published scoring systems for deciding between chelation treatment and liver transplantation in patients with chronic decompensated and fulminant WD. Model for end-stage liver disease (MELD) score, as well as WD prognostic index (WPI) and its recently revised version (RWPI) were evaluated as predictors of the safety for chelation therapy. A group of 14 adult patients with clecompensated chronic WD who improved on penicillamine treatment were compared with 21 patients with fulminant WD. The diagnosis of WD was based on increased urinary copper excretion and confirmed by elevated liver copper content and/or mutation analysis of the WD gene. The MELD score, WPI, and RWPI were calculated for all patients with WD. The accuracy of the MELD score, WPI, and RWPI for prediction of response to chelation therapy in patients with decompensated chronic WD was 0.968, 0.980, and 0.993, respectively. None of the decompensated chronic WD patients had a MELD score >30, RWPI >11, or WPI >7. RWPI showed the highest accuracy and the lowest false negativity compared with WPI and MELD. In conclusion, our data indicate that RWPI, originally proposed for pediatric patients, is also useful for adults. © 2006 AASLD.",accuracy;adult;aged;article;calculation;chelation therapy;chronic disease/su [Surgery];chronic disease/th [Therapy];clinical article;clinical protocol;controlled study;diagnostic procedure;female;gene mutation;human;liver failure;liver transplantation;male;prediction;priority journal;prognosis;scoring system;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];copper;penicillamine/dt [Drug Therapy],"Petrasek, J.;Jirsa, M.;Sperl, J.;Kozak, L.;Taimr, P.;Spicak, J.;Filip, K.;Trunecka, P.",2007,,http://dx.doi.org/10.1002/lt.20920,0,0,
2035,Liver disease in pregnancy,"Children of hepatitis B surface antigen-positive mothers should be vaccinated on the first day of life and at 1, 3 and 12 months. In mothers with a high viral load, a role for viral suppression with lamivudine during the third trimester has also been suggested. Hepatic adenoma should be a contraindication to pregnancy or resected first; it may grow rapidly and rupture with life-threatening intraperitoneal haemorrhage. Obstetric cholestasis usually presents as pruritus of the extremities. Ursodeoxycholic acid, 10 mg/kg/day, improved symptoms and biochemistry in the mother in a few reported trials and there have been no reports of adverse effects on the baby. The fetus is at increased risk of premature labour, fetal distress and stillbirth, but elective delivery at 37-38 weeks avoids these in almost all cases. HELLP syndrome - the defining features are: haemolysis (microangiopathic), elevated liver enzymes (ALT and aspartate aminotransferase 2-10 times upper limit of normal) and low platelets (<100,000 x 10<sup>9</sup>/litre). Early delivery is helpful, though the condition may progress or even develop de novo post-partum, peaking at about 48 hours after delivery. In full-blown eclampsia, rupture of the liver with massive intraperitoneal haemorrhage may occur, with high mortality. Acute fatty liver of pregnancy is severe but uncommon (1/15,000). Onset is confined to the third trimester, typically with vomiting, upper abdominal pain, anorexia and malaise. Acute fatty liver of pregnancy is common when the baby has a genetic defect of long-chain hydroxyacyldehydrogenase (LCHAD). © 2006.",fatty liver;HELLP syndrome;hepatic adenoma;hepatitis B;liver disease;obstetric cholestasis;pregnancy;abdominal pain;anorexia;autoimmune hepatitis/dt [Drug Therapy];biochemistry;Budd Chiari syndrome;cholecystectomy;cholestasis/dt [Drug Therapy];delivery;disease severity;eclampsia/co [Complication];fatty liver/co [Complication];female;fetus distress/co [Complication];gallstone/su [Surgery];graft recipient;graft rejection/co [Complication];graft rejection/dt [Drug Therapy];graft rejection/pc [Prevention];hemoperitoneum/co [Complication];hepatitis B/dt [Drug Therapy];hepatitis B/et [Etiology];hepatitis B/pc [Prevention];Hepatitis B virus;hepatitis E/et [Etiology];Hepatitis E virus;human;hyperemesis gravidarum/co [Complication];liver adenoma/su [Surgery];liver cirrhosis;liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/pc [Prevention];liver resection;liver rupture/co [Complication];liver transplantation;malaise;mortality;premature labor/co [Complication];prenatal screening;priority journal;pruritus;review;stillbirth;third trimester pregnancy;thrombocyte count;virus load;vomiting;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];azathioprine/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];hepatitis B surface antigen/ec [Endogenous Compound];hepatitis B vaccine/dt [Drug Therapy];lamivudine/dt [Drug Therapy];oxidoreductase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];ursodeoxycholic acid/to [Drug Toxicity],"Elias, E.",2007,February,http://dx.doi.org/10.1016/j.mpmed.2006.11.008,0,0,
2036,Wilson's disease,"Wilson's disease is an autosomal recessive disorder of hepatic copper disposition caused by mutations in the gene ATP7B, located on chromosome 13. This gene encodes a P-type ATPase, known as the Wilson ATPase, which functions within hepatocytes to move copper across intracellular membranes. The copper-transporting action directly supports production of the ferroxidase ceruloplasmin, in which copper is incorporated, as well as excretion of copper into bile. Consequently, in Wilson's disease, serum concentrations of copper are low and hepatic retention of copper develops, leading to liver injury. Wilson's disease can present as hepatic, neurological or psychiatric disease; clinical phenotypes are highly varied. Other organ systems may also be involved. Although the usual age range for clinical presentation is 5-45 years, younger children and older adults may present with this disease. Clinical investigations include tests of liver function, cerebral imaging, serum ceruloplasmin and copper, basal 24-hour urinary copper measurement, and hepatic parenchymal copper concentration. Genetic diagnosis is complex and best used for family studies or in populations known to have a limited repertoire of mutations. Treatment is usually very effective and consists of life-long administration of a chelator (D-penicillamine or trientine) or of zinc in pharmacological doses. Liver transplantation is mandatory for patients presenting with fulminant hepatic failure (coagulopathy, encephalopathy, massive intravascular haemolysis, renal failure, elevated aminotransferases, subnormal alkaline phosphatase) or for those whose liver disease is not responding to usual treatment. Liver cancer is extremely uncommon in patients with Wilson's disease but screening may be appropriate for older patients. © 2006 Elsevier Ltd. All rights reserved.",atp7b;ceruloplasmin;cirrhosis;copper;hepatolenticular degeneration;movement disorders;Wilson ATPase;Wilson's disease;alcohol withdrawal;aplastic anemia/si [Side Effect];autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/et [Etiology];biliary excretion;blood clotting disorder;blood level;bone marrow suppression/si [Side Effect];brain disease;clinical examination;clinical feature;concentration (parameters);diet restriction;drug efficacy;drug substitution;drug withdrawal;family study;gene mutation;genetic analysis;human;intravascular hemolysis;kidney disease/si [Side Effect];kidney failure;liver cancer/co [Complication];liver cell;liver failure/co [Complication];liver failure/su [Surgery];liver function test;liver injury/co [Complication];liver parenchyma;liver transplantation;lupus like syndrome/si [Side Effect];membrane transport;mental disease;neuroimaging;neurologic disease/si [Side Effect];phenotype;population research;priority journal;protein function;review;skin disease/si [Side Effect];urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];adenosine triphosphatase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent;copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Roberts, E. A.",2007,February,http://dx.doi.org/10.1016/j.mpmed.2006.11.002,0,0,1708
2037,Wilson's disease- A treatable metabolic disease. [German],Wilson's disease is an autosomal recessive disorder of the hepatic copper excretion. Clinical manifestation is between the 5<sup>th</sup> and 40 <sup>th</sup> year with hepatic or extrapyramidal symptoms and the course of the disease is progressive if the diagnosis is not done early and no adequate therapy is started. The genetic defect is caused by a mutation of the ATPase 7B gene on chromosome 13 which codes for an enzyme necessary for the excretion of copper in the bile. All therapeutical strategies are directed towards a negative copper balance either by a reduced copper absorption (zinc) in the gut or an increased copper elimination (chelating agens d-penicillamine and trientine). The therapy should be chosen in regard to the stadium of the disease and the copper metabolism has to be controlled in regular intervals. © 2007 Schattauer GmbH.,Copper;Negative copper balance;Outosomal recessive disease;clinical feature;colitis/si [Side Effect];copper metabolism;food and drug administration;gastrointestinal disease/si [Side Effect];gene mutation;human;kidney disease/si [Side Effect];laboratory test;lupus erythematosus/si [Side Effect];monotherapy;myasthenia gravis/si [Side Effect];myositis/si [Side Effect];nephritis/si [Side Effect];review;rhabdomyolysis/si [Side Effect];unspecified side effect/si [Side Effect];urticaria/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];gluconate zinc/dt [Drug Therapy];gluconate zinc/po [Oral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];pyridoxine/dt [Drug Therapy];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];unclassified drug;univar;zinc/cb [Drug Combination];zinc/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration],"Straube, A.;Hermann, W.",2007,,,0,0,
2038,Nonsense mutations of the ZFHX1B gene in two Japanese girls with Mowat-Wilson syndrome,"Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B). MWS has been reported in association with Hirschsprung disease (HSCR). MWS is sometimes difficult to diagnose clinically, especially when HSCR is absent. Thus, it is necessary to detect gene abnormalities at the molecular level. Here we report two Japanese girls with MWS, who showed a distinct facial phenotype, severe intellectual disability and epileptic seizures. Major congenital anomalies of the patients were very different. Patient 1 suffered from severe congenital heart disease, but did not show apparent HSCR. Patient 2 suffered from typical HSCR and underwent surgical treatment, but did not have congenital heart disease. According to the gene analysis using white blood cells, they had nonsense mutations in ZFHX1B, R695X and Q433X, respectively. In conclusion, molecular genetic analysis of ZFHX1B is important for a definite diagnosis of MWS which has a wide phenotypic spectrum of congenital anomalies.",Mowat-Wilson syndrome;Nonsense mutation;sip1;zfhx1b;article;case report;child;clinical feature;female;gene;gene mutation;genetic analysis;Hirschsprung disease;human;mental deficiency/cn [Congenital Disorder];mental deficiency/di [Diagnosis];molecular genetics;mowat wilson syndrome/cn [Congenital Disorder];mowat wilson syndrome/di [Diagnosis];polymerase chain reaction;zinc finger homeobox 1b gene,"Sasongko, T. H.;Hamim, A.;Gunadi, S.;Myeong, J. L.;Koterazawa, K.;Nishio, H.",2007,,,0,0,
2039,Plasmapheresis for hemolytic crisis and impending acute liver failure in Wilson disease,"Wilsonian crisis is fatal unless copper removal is initiated early and liver transplantation is performed for patients that fulfill criteria for a poor outcome. We report a patient presenting with severe hemolysis and impending acute liver failure that made a rapid recovery with prompt initiation of plasmapheresis and chelation therapy. Rapid copper removal by plasmapheresis alleviated hemolysis and liver injury. A review of the literature was performed examining the use of plasmapheresis and albumin dialysis with continuous veno-venous hemodialysis or molecular adsorbents and recirculating system. © 2007 Wiley-Liss, Inc.",Acute liver failure;Continuous veno-venous hemodialysis;Hemolytic anemia;Molecular adsorbents and recirculating system;Plasmapheresis;adult;anamnesis;article;case report;clinical examination;clinical feature;drug withdrawal;female;hemolysis/dt [Drug Therapy];hemolysis/th [Therapy];human;human tissue;laboratory test;liver biopsy;liver failure;liver transplantation;lung infiltrate/si [Side Effect];respiratory tract disease/dt [Drug Therapy];thrombocytopenia/si [Side Effect];unspecified side effect/si [Side Effect];Wilson disease;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Asfaha, S.;Almansori, M.;Qarni, U.;Gutfreund, K. S.",2007,,http://dx.doi.org/10.1002/jca.20140,0,0,
2040,"Wilson disease-A practical approach to diagnosis, treatment and follow-up","Wilson disease is an inherited, autosomal recessive, copper accumulation and toxicity disorder that affects about 30 individuals per million. This rare disease is caused by mutations in the gene encoding a copper-transporting P-type ATPase, which is important for copper excretion into bile, leading to copper accumulation in the liver. Toxic copper concentrations can also be found in the brain and kidney, and clinical phenotypes include hepatic, haemolytic, neurologic and psychiatric diseases. Diagnosis is based on the combination of clinical features and findings such as increased urinary copper excretion, reduced levels of serum ceruloplasmin, high concentrations of copper in liver tissues and Kayser-Fleischer rings. Genetic studies are also becoming available for clinical use, but the utility of direct mutation analysis is limited. Wilson disease can be treated, and early diagnosis is essential: the goal of therapy is to reduce copper accumulation either by enhancing its urinary excretion or by decreasing its intestinal absorption. Medical therapies include penicillamine, trientine, zinc and tetrathiomolibdate. Liver transplantation is a relatively successful treatment option when medical therapy fails or in case of acute liver failure, even though it is also characterized by short- and long-term complications. © 2007 Editrice Gastroenterologica Italiana S.r.l.",Copper;Diagnosis;Liver transplantation;Wilson disease;acute hepatitis/si [Side Effect];anemia/si [Side Effect];aplastic anemia/si [Side Effect];arthropathy/si [Side Effect];autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/su [Surgery];bile flow;bone marrow depression/si [Side Effect];bone marrow toxicity/si [Side Effect];brain;cholestasis/si [Side Effect];clinical feature;clinical protocol;clinical trial;concentration response;degeneration/si [Side Effect];diagnostic approach route;diet therapy;drug dose increase;drug eruption/si [Side Effect];drug fever/si [Side Effect];drug hypersensitivity/si [Side Effect];drug mechanism;drug substitution;drug withdrawal;early diagnosis;follow up;gene mutation;genetic analysis;human;intestine absorption;kidney;liver disease;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];mental disease;neurologic disease/si [Side Effect];neutropenia/si [Side Effect];phenotype;pregnancy;proteinuria/si [Side Effect];pyridoxine deficiency/dt [Drug Therapy];pyridoxine deficiency/si [Side Effect];short survey;side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];skin disease/si [Side Effect];stomach irritation/si [Side Effect];thrombocytopenia/si [Side Effect];urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];copper/to [Drug Toxicity];corticosteroid/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pyridoxine/cb [Drug Combination];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];zinc/pd [Pharmacology];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Medici, V.;Rossaro, L.;Sturniolo, G. C.",2007,July,http://dx.doi.org/10.1016/j.dld.2006.12.095,0,0,
2041,Hepatic steatosis in patients with Wilson disease and mutation L708P. [Spanish],,adolescent;child;clinical article;clinical feature;conference paper;controlled study;echography;enzyme defect;fatty liver;female;gene mutation;histopathology;human;human tissue;liver cirrhosis/di [Diagnosis];male;retrospective study;Wilson disease;aminotransferase/ec [Endogenous Compound];penicillamine,"Gonzalez Santana, D.;Arias Santos Ma, D.;Afonso Rodriguez, O.;Rial Gonzalez, R.;Espino Gonzalez, A.;Bello Naranjo, A. Ma;Ramos Varela, J. C.;Pena Quintana, L.",2007,April,,0,0,
2042,Recent advances in approach to treatment of genetic disorders: Clinician's perspective,"There is no cure for most of the genetic disorders. The only option in most situations is prevention by counseling and prenatal diagnosis. However, over a decade, with the completion of the human genome project and other advances there is better understanding of pathogenesis, improvement in diagnostic strategies and various treatment avenues are opening up for these disorders. The aim of this article is to make the pediatricians aware of the approaches to treatment of common genetic disorders and recent available therapeutic interventions.","Enzyme replacement therapy;Genetic disorders;Stem cell;acidemia/dt [Drug Therapy];acute intermittent porphyria;adenosine deaminase deficiency;adrenoleukodystrophy/th [Therapy];albinism;alpha 1 antitrypsin deficiency;beta thalassemia/th [Therapy];biotinidase deficiency;bone marrow transplantation;chondrodysplasia/su [Surgery];cleft lip palate/su [Surgery];congenital adrenal hyperplasia/cn [Congenital Disorder];congenital heart disease/cn [Congenital Disorder];cord blood stem cell transplantation;cystinosis/dt [Drug Therapy];degenerative disease/dt [Drug Therapy];diagnostic test;disorders of amino acid and protein metabolism;drug cost;drug efficacy;Duchenne muscular dystrophy;embryonic stem cell;enzyme deficiency/dt [Drug Therapy];enzyme replacement;Fabry disease/dt [Drug Therapy];familial colon polyposis/su [Surgery];familial hypercholesterolemia;fucosidosis/th [Therapy];galactokinase deficiency/dt [Drug Therapy];galactosemia/dt [Drug Therapy];Gaucher disease/dm [Disease Management];Gaucher disease/dt [Drug Therapy];Gaucher disease/th [Therapy];gene therapy;genetic disorder/di [Diagnosis];genetic disorder/dm [Disease Management];genetic disorder/dt [Drug Therapy];globoid cell leukodystrophy/th [Therapy];glucose 6 phosphate dehydrogenase deficiency;glycogen storage disease type 1;glycogen storage disease type 2/dt [Drug Therapy];glycogen storage disease type 3;goiter;gout/dt [Drug Therapy];growth hormone deficiency/dt [Drug Therapy];hemophilia;hepatorenal tyrosinemia;homocystinuria;human;Hurler syndrome/dm [Disease Management];Hurler syndrome/dt [Drug Therapy];Hurler syndrome/th [Therapy];hypochondroplasia/dt [Drug Therapy];isovaleric acidemia/dt [Drug Therapy];low drug dose;lysosome storage disease/th [Therapy];malignant infantile osteopetrosis/th [Therapy];mannosidosis/th [Therapy];maple syrup urine disease/dt [Drug Therapy];Marfan syndrome/dt [Drug Therapy];Maroteaux Lamy syndrome/dm [Disease Management];Maroteaux Lamy syndrome/dt [Drug Therapy];Maroteaux Lamy syndrome/th [Therapy];metachromatic leukodystrophy/th [Therapy];mucopolysaccharidosis type 7/th [Therapy];Niemann Pick disease/th [Therapy];Noonan syndrome/dt [Drug Therapy];orotic aciduria;osteogenesis imperfecta/dt [Drug Therapy];osteoporosis/th [Therapy];phenylketonuria/dt [Drug Therapy];pluripotent stem cell;recommended drug dose;review;sickle cell anemia/dt [Drug Therapy];stem cell transplantation;thalassemia/th [Therapy];thalassemia intermedia;treatment outcome;Turner syndrome/dt [Drug Therapy];urea cycle disorder/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];xeroderma pigmentosum;agalsidase alfa/do [Drug Dose];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/iv [Intravenous Drug Administration];agalsidase beta/do [Drug Dose];agalsidase beta/dt [Drug Therapy];agalsidase beta/iv [Intravenous Drug Administration];alendronic acid/ad [Drug Administration];alendronic acid/cm [Drug Comparison];alendronic acid/dt [Drug Therapy];alendronic acid/po [Oral Drug Administration];alendronic acid/pe [Pharmacoeconomics];allopurinol/dt [Drug Therapy];anticonvulsive agent/dt [Drug Therapy];arylbutyric acid derivative/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];beta glucocerebrosidase/do [Drug Dose];beta glucocerebrosidase/dt [Drug Therapy];beta glucocerebrosidase/iv [Intravenous Drug Administration];branched chain amino acid/dt [Drug Therapy];carnitine/dt [Drug Therapy];galactose/dt [Drug Therapy];galsulfase/dt [Drug Therapy];galsulfase/pe [Pharmacoeconomics];glucosylceramidase/dt [Drug Therapy];glycine/dt [Drug Therapy];growth hormone/dt [Drug Therapy];hydroxyurea/dt [Drug Therapy];imiglucerase/dt [Drug Therapy];imiglucerase/pe [Pharmacoeconomics];isoenzyme/dt [Drug Therapy];laronidase/dt [Drug Therapy];laronidase/iv [Intravenous Drug Administration];laronidase/pe [Pharmacoeconomics];Lorenzo oil/dt [Drug Therapy];mercaptamine/dt [Drug Therapy];mevinolin/dt [Drug Therapy];pamidronic acid/ad [Drug Administration];pamidronic acid/cm [Drug Comparison];pamidronic acid/dt [Drug Therapy];pamidronic acid/iv [Intravenous Drug Administration];pamidronic acid/pe [Pharmacoeconomics];penicillamine/dt [Drug Therapy];phenylacetic acid/dt [Drug Therapy];phenylalanine/dt [Drug Therapy];recombinant glucan 1,4 alpha glucosidase/dt [Drug Therapy];recombinant glucan 1,4 alpha glucosidase/pe [Pharmacoeconomics];recombinant growth hormone/dt [Drug Therapy];unclassified drug;unindexed drug","Gupta, N.;Kabra, M.",2007,May,,0,0,
2043,Therapy Insight: Inborn errors of metabolism in adult neurology - A clinical approach focused on treatable diseases,"Inborn errors of metabolism (IEMs) are genetic disorders characterized by dysfunction of an enzyme or other protein involved in cellular metabolism. In most cases, IEMs involve the nervous system. The first clinical symptoms of IEMs usually present in infancy, but in an unknown proportion of cases they can appear in adolescence or adulthood. In this Review, we focus on treatable IEMs, presenting acutely or chronically, that can be diagnosed in an adult neurology department. To make our presentation readily usable by clinicians, the Review is subdivided into eight sections according to the main clinical presentations: emergencies (acute encephalopathies and strokes), movement disorders, peripheral neuropathies, spastic paraparesis, cerebellar ataxia, psychiatric disorders, epilepsy and leukoencephalopathies. Our aim is to present simple guidelines to enable neurologists to avoid overlooking a treatable metabolic disease.",abetalipoproteinemia/di [Diagnosis];abetalipoproteinemia/dt [Drug Therapy];abetalipoproteinemia/et [Etiology];acute brain disease;acute intermittent porphyria/di [Diagnosis];acute intermittent porphyria/dt [Drug Therapy];acute intermittent porphyria/et [Etiology];alpha tocopherol deficiency/di [Diagnosis];alpha tocopherol deficiency/dt [Drug Therapy];alpha tocopherol deficiency/et [Etiology];ataxia;autosomal recessive inheritance;biotin responsive basal ganglia disease/di [Diagnosis];biotin responsive basal ganglia disease/dt [Drug Therapy];biotinidase deficiency/di [Diagnosis];biotinidase deficiency/dt [Drug Therapy];cerebrotendinous xanthomatosis/di [Diagnosis];cerebrotendinous xanthomatosis/dt [Drug Therapy];cerebrovascular accident/co [Complication];clinical feature;clinical trial;cobalamin c disease/di [Diagnosis];cobalamin c disease/dt [Drug Therapy];cystathionine beta synthase deficiency/di [Diagnosis];cystathionine beta synthase deficiency/dt [Drug Therapy];cystathionine beta synthase deficiency/th [Therapy];diet therapy;drug megadose;enzyme replacement;epilepsy;evidence based medicine;Fabry disease/di [Diagnosis];Fabry disease/th [Therapy];fatty acid oxidation defect/di [Diagnosis];fatty acid oxidation defect/dt [Drug Therapy];fatty acid oxidation defect/th [Therapy];folic acid deficiency/di [Diagnosis];folic acid deficiency/dt [Drug Therapy];Gaucher disease/di [Diagnosis];Gaucher disease/th [Therapy];glucose transporter 1 deficiency/di [Diagnosis];glucose transporter 1 deficiency/th [Therapy];glutaric aciduria type 1/di [Diagnosis];glutaric aciduria type 1/dt [Drug Therapy];guanosine triphosphate cyclohydrolase I deficiency/di [Diagnosis];guanosine triphosphate cyclohydrolase I deficiency/dt [Drug Therapy];human;hyperglycinemia/di [Diagnosis];hyperglycinemia/dt [Drug Therapy];hypobetalipoproteinemia/di [Diagnosis];hypobetalipoproteinemia/dt [Drug Therapy];hypobetalipoproteinemia/et [Etiology];inborn error of metabolism/di [Diagnosis];inborn error of metabolism/dt [Drug Therapy];inborn error of metabolism/et [Etiology];inborn error of metabolism/th [Therapy];leukoencephalopathy;low drug dose;maple syrup urine disease/di [Diagnosis];maple syrup urine disease/th [Therapy];mental disease;metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];metabolic disorder/th [Therapy];methylene tetrahydrofolate reductase deficiency/di [Diagnosis];methylene tetrahydrofolate reductase deficiency/dt [Drug Therapy];motor dysfunction;neurologic disease;pathophysiology;peripheral neuropathy;phenylketonuria/di [Diagnosis];phenylketonuria/th [Therapy];priority journal;propionic aciduria/di [Diagnosis];propionic aciduria/dt [Drug Therapy];pyruvate dehydrogenase deficiency/di [Diagnosis];pyruvate dehydrogenase deficiency/dt [Drug Therapy];pyruvate dehydrogenase deficiency/th [Therapy];pyruvoyl tetrahydrobiopterin synthase deficiency/di [Diagnosis];pyruvoyl tetrahydrobiopterin synthase deficiency/dt [Drug Therapy];Refsum disease/di [Diagnosis];Refsum disease/th [Therapy];review;screening test;serine deficiency/di [Diagnosis];serine deficiency/dt [Drug Therapy];spastic paraplegia;systematic review;triple h syndrome/di [Diagnosis];triple h syndrome/dt [Drug Therapy];tyrosine hydrolase deficiency/di [Diagnosis];tyrosine hydrolase deficiency/dt [Drug Therapy];ubidecarenone deficiency/di [Diagnosis];ubidecarenone deficiency/dt [Drug Therapy];urea cycle disorder/di [Diagnosis];urea cycle disorder/dt [Drug Therapy];urea cycle disorder/th [Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];X chromosome linkage;alpha tocopherol/dt [Drug Therapy];arginine/dt [Drug Therapy];arylbutyric acid derivative/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];betaine/dt [Drug Therapy];biotin/dt [Drug Therapy];chelating agent/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];citrulline/dt [Drug Therapy];cobalamin/dt [Drug Therapy];dextromethorphan/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];folinic acid/dt [Drug Therapy];glucose/dt [Drug Therapy];heme/dt [Drug Therapy];hydroxocobalamin/dt [Drug Therapy];ketamine/dt [Drug Therapy];levodopa/do [Drug Dose];levodopa/dt [Drug Therapy];medium chain triacylglycerol/dt [Drug Therapy];ornithine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];retinol/dt [Drug Therapy];serine/dt [Drug Therapy];thiamine/dt [Drug Therapy];trientine/dt [Drug Therapy];ubidecarenone/dt [Drug Therapy];unindexed drug;zinc,"Sedel, F.;Lyon-Caen, O.;Saudubray, J. M.",2007,May,http://dx.doi.org/10.1038/ncpneuro0494,0,0,
2044,Pharmacophores and biological activities of severe acute respiratory syndrome viral protease inhibitors,"Coronaviruses usually cause diseases with minor syndromes. However, an infectious disease caused by a novel human coronavirus induced severe acute respiratory syndrome (SARS). This disease first occurred in late 2002 and rapidly spread from its origin in southern China to > 25 countries during the 2003 epidemic. It affected ~ 8000 patients resulting in ~ 800 fatalities, a high mortality rate. To combat the disease, scientists have carried out cell-based assays to find the inhibitors on viral replication or focused on specific targets for developing their inhibitors as possible therapeutic agents. A promising target for SARS drug development is a chymotrypsin-like cysteine protease, a main protease responsible for the maturation of functional proteins in the life cycle of the SARS coronavirus. Several groups of inhibitors have been identified through high-throughput screening and rational drug design. The inhibitors reported in the literature and described in the patents are summarised in this review. These compounds may be useful to combat SARS if it reoccurs in the future and in developing new drugs for other coronaviruses with the main proteases. © 2007 Informa UK Ltd.",Cysteine protease;Fluorescence assay;High-throughput screening;Rational drug design;SARS coronavirus;antibiotic sensitivity;binding affinity;computer model;Coronavirus;drug design;drug screening;enzyme inhibition;high throughput screening;human;ic 50;molecular docking;nonhuman;pharmacophore;protein function;protein structure;quantitative structure activity relation;review;severe acute respiratory syndrome/dt [Drug Therapy];virus infection/dt [Drug Therapy];virus infection/pc [Prevention];virus inhibition;virus replication;virus transmission;Wilson disease/dt [Drug Therapy];anilide;antivirus agent/an [Drug Analysis];aziridine derivative;benzotriazole derivative;cinanserin;cysteine proteinase/ec [Endogenous Compound];escin;etacrynic acid;glycopeptide/dt [Drug Therapy];hexachlorophene/an [Drug Analysis];isatin derivative;lopinavir/dt [Drug Therapy];lopinavir plus ritonavir;mac 13985/an [Drug Analysis];mac 22272/an [Drug Analysis];mac 30731/an [Drug Analysis];mac 5576/an [Drug Analysis];mac 8120/an [Drug Analysis];phenylmercuric acetate/an [Drug Analysis];proteinase inhibitor;reserpine;ristocetin/dt [Drug Therapy];rupintrivir;tannin;teicoplanin/dt [Drug Therapy];thiomersal/an [Drug Analysis];unclassified drug;unindexed drug;vancomycin/dt [Drug Therapy];zenullose;zinc acetate/dt [Drug Therapy];zinc complex/dt [Drug Therapy];zincum gluconicum/dt [Drug Therapy],"Wang, H. M.;Liang, P. H.",2007,May,http://dx.doi.org/10.1517/13543776.17.5.533,0,0,
2045,Serum copper in Alzheimer,"Abnormalities in the homeostasis of brain metals in Alzheimer's disease (AD) can contribute to set up environmental conditions where beta-amyloid toxicity and deposition are promoted within areas at risk. Recent studies in man have described possible implications of copper in the AD pathogenesis. In particular, evidence collected in our laboratory in the past six years shows that abnormalities in copper distribution originating from blood stream variations correlate with functional and structural brain deficits in AD. Despite these works supporting a damaging role of copper, new studies hypothesize a protective role. In fact, some recent studies have shown that a decrease of serum copper in man correlates with a worse neuropsychological performance. However, this apparent discrepancy concerns the absolute serum copper levels and can be overcome by considering the fraction of non-ceruloplasmin-copper (NCC).",beta-Amyloid;Alzheimer's disease;Ceruloplasmin;Copper;eeg;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];article;copper blood level;disease marker;drug efficacy;drug withdrawal;human;multiinfarct dementia/et [Etiology];nonhuman;oxidative stress;pathogenesis;risk factor;subacute myelooptic neuropathy/si [Side Effect];unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];amyloid beta protein/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];clioquinol/ae [Adverse Drug Reaction];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];copper/ec [Endogenous Compound];deferoxamine/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy],"Squitti, R.;Rossini, P. M.",2007,,,0,0,
2046,A copper determination method based on the reaction between 2-(5-nitro-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino) phenol (nitro-PAPS) and copper for use in urine copper measurement and application to automation,"Aim: To develop a sensitive automated colorimetric urine copper determination method using a water soluble compound, 2-(5-nitro-2-pyridylazo)-5- (N-propyl-N-sulfopropylamino) phenol (nitro-PAPS), as a ligand. Materials and Methods: The new photometric method using sodium dodecyl sulfate (SDS)-ascorbic acid to dissociate copper from proteins in acetate buffer (pH 3.2) and nitro-PAPS as ligand was also adapted to an automated analyzer. Copper concentrations were determined by atomic absorption spectrophotometric method and by photometric method in 24 h urine samples of patients (n = 100) with various types of diseases including Wilson's disease (n = 12), diabetes mellitus (n = 34), osteoporosis (n = 27), nephrotic syndrome (n = 17), and rheumatoid arthritis (n = 10). Results: There was a statistically significant correlation (P < 0.01) between our new method and the atomic absorption spectrophotometric method (y = 0.994x + 0.207, Sy/x = 1.776), and the photometric method was linear up to 200 mug/l concentration. Other complexing metals (Zn<sup>+2</sup> and Fe<sup>+2</sup>) had no interfering effect on the Cu-nitro-PAPS reaction. The analytical recovery of copper was between 90% and 107% (mean 98%). Within-run and between-run CVs were <5% in normal and high copper containing urine pools. Conclusions: We have developed a new sensitive and reliable automated colorimetric urine copper determination method. © TUBITAK.",Nitro-PAPS;Photometric method;Urine copper;analyzer;article;atomic absorption spectrometry;colorimetry;controlled study;diabetes mellitus;human;major clinical study;nephrotic syndrome;photometry;rheumatoid arthritis;urinalysis;Wilson disease;2-(5-nitro-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol;acetic acid;ascorbic acid;buffer;copper;dodecyl sulfate sodium;metal complex;phenol derivative;unclassified drug,"Ipcioglu, O. M.;Ozcan, O.;Gultepe, M.",2007,April,,0,0,
2047,Wilson's desease: Case report and literature review. [Spanish],"A case of Wilson disease in a woman of 22 years is reported. There are only antecedents of primary amenorrhea with the diagnose at the 17 years old of polycystic ovarian. The disease has 2 years of evolution with progressive heavy tremor of right hand, sialorrea, rigidity of left arm and dysphagia. In the ophtalmologic examination was found the Kayser-Fleischer ring. The MRI showed diffuse hyperintensity of basal ganglia and degeneration of lenticular nucleus, compatible with Wilson's disease. The liver biopsy shown macronodular cirrhosis with regeneration nodules and minimum activity data. It was made genomic sequence of DNA that showed homozygotic mutation for the amino acids sequence H1069Q, and c3207C>a in the exon 14 of gene ATP7B. The patient received treatment of 8 weeks with ammonium tetratiomolibdate, zinc acetate and D-penicilamine with improvement of the neurologic symptoms.",Ceruloplasmin;Disease of Wilson;Ring of Kayser-Fleischer;adult;amenorrhea;article;basal ganglion;brain function;case report;disease course;disease duration;DNA sequence;dysphagia;eye examination;female;gene mutation;genome;hand tremor;histopathology;homozygote;human;human tissue;hypersalivation;laparoscopy;liver biopsy;liver cirrhosis;liver regeneration;muscle hypertonia;muscle tone;nuclear magnetic resonance imaging;ovary polycystic disease;proprioception;rigidity;tissue degeneration;Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/cb [Drug Combination];tetrathiomolybdate ammonium/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy],"Hernandez, M. A. L.;Rufino, M. S.",2007,September/October,,0,0,
2048,Therapeutic profile of orphan medicines,"Purpose: To characterise the therapeutic profile of orphan medicines. Materials and Methods: A cross-sectional study was performed during 2 months in a convenience sample of seven hospital pharmacy services, in the region of Lisbon. Data were collected, from pharmaceutical service's records. Results: A total of 18 orphan medicines, were dispensed to 355 patients with rare diseases. Most patients were adults (76.4%). Premature and neonates accounted with 50.0% of the paediatric patients. Differences were not found between the proportion of male and female patients across age groups (p = 0.762). Only 18.3% were inpatients. A high proportion of paediatric inpatients (58.3%) were seen in relation to adult inpatients (5.9%) (P = 0.001). In general, anti-neoplastic and immunomodulating agents for rare cancers were the most frequent dispensed medicines (51.3%). In relation to paediatrics, Caffeine Citrate for primary apnoea of premature newborns had the higher frequency distribution (57.1%). Five (71.4%) medicines dispensed for paediatrics, do not have market authorisation and the remaining (28.6%) were used off-label. For pulmonary arterial hypertension 19 of 27 patients (70.3%) were treated with Bosentan. According to evidence-based clinical practice guidelines, Bosentan has a good level of evidence and substantial benefit: grade of recommendation A. Conclusions: Most orphan medicines dispensed to paediatrics and adults were not licensed. A special pharmacovigilance program and a risk management plan through the entire life cycle should be implemented, towards effectiveness and safety of orphan medicines. Copyright © 2006 John Wiley & Sons, Ltd.",Drug utilisation studies;Orphan medicines;Rare diseases;Therapeutic profile;adolescent;adult;age;aged;angioneurotic edema/dt [Drug Therapy];article;cancer/dt [Drug Therapy];child;chronic myeloid leukemia/dt [Drug Therapy];controlled study;drug efficacy;drug safety;drug surveillance program;evidence based practice;Fabry disease/dt [Drug Therapy];female;gastrointestinal stromal tumor/dt [Drug Therapy];hepatitis B/dt [Drug Therapy];hospital patient;hospital pharmacy;human;infant;information processing;licence;major clinical study;male;multiple myeloma/dt [Drug Therapy];newborn;newborn apnea/dt [Drug Therapy];off label drug use;pharmaceutical care;Portugal;practice guideline;prematurity;prevalence;priority journal;pulmonary hypertension/dt [Drug Therapy];risk management;sex difference;sickle cell anemia/dt [Drug Therapy];statistical significance;Wilson disease/dt [Drug Therapy];alpha 1 antitrypsin/dt [Drug Therapy];anagrelide/dt [Drug Therapy];antineoplastic agent/dt [Drug Therapy];arsenic trioxide/dt [Drug Therapy];bosentan/dt [Drug Therapy];caffeine citrate/dt [Drug Therapy];complement component C1s inhibitor/dt [Drug Therapy];denileukin diftitox/dt [Drug Therapy];hepatitis B antibody/dt [Drug Therapy];hydroxyurea/dt [Drug Therapy];iloprost/dt [Drug Therapy];iloprost/ih [Inhalational Drug Administration];imatinib/dt [Drug Therapy];immunomodulating agent/dt [Drug Therapy];nitisinone/dt [Drug Therapy];orphan drug/dt [Drug Therapy];pancreatin/dt [Drug Therapy];stiripentol/dt [Drug Therapy];thalidomide/dt [Drug Therapy];tobramycin/dt [Drug Therapy];tobramycin/ih [Inhalational Drug Administration];trientine/dt [Drug Therapy],"Teixeira de Barros, C. M.;Papoila, A. L.",2007,April,http://dx.doi.org/10.1002/pds.1315,0,0,
2049,Wilson's disease,"Wilson's disease is an autosomal-recessive disorder caused by mutation in the ATP7B gene, with resultant impairment of biliary excretion of copper. Subsequent copper accumulation, first in the liver but ultimately in the brain and other tissues, produces protean clinical manifestations that may include hepatic, neurological, psychiatric, ophthalmological, and other derangements. Genetic testing is impractical because of the multitude of mutations that have been identified, so accurate diagnosis relies on judicious use of a battery of laboratory and other diagnostic tests. Lifelong palliative treatment with a growing stable of medications, or with liver transplantation if needed, can successfully ameliorate or prevent the progressive deterioration and eventual death that would otherwise inevitably ensue. This article discusses the epidemiology, genetics, pathophysiology, clinical features, diagnostic testing, and treatment of Wilson's disease. Copyright © 2007 by Thieme Medical Publishers, Inc.",Ceruloplasmin;Copper;Penicillamine;Wilson's disease;Zinc;ageusia/si [Side Effect];anemia/si [Side Effect];autosomal recessive disorder;biliary excretion;bioaccumulation;bone marrow depression/si [Side Effect];clinical assessment;clinical feature;copper blood level;diagnostic accuracy;diagnostic test;disease course;drug withdrawal;eosinophilia/si [Side Effect];fever/si [Side Effect];gene mutation;Goodpasture syndrome/si [Side Effect];human;laboratory diagnosis;leukopenia/si [Side Effect];liver;liver transplantation;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];myasthenia like syndrome/si [Side Effect];nephrotic syndrome/si [Side Effect];neuroimaging;neurologic disease;ophthalmology;palliative therapy;pathophysiology;polyarthritis/si [Side Effect];practice guideline;priority journal;rash/si [Side Effect];retina hemorrhage/si [Side Effect];review;thrombocytopenia/si [Side Effect];treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy],"Pfeiffer, R. F.",2007,April,http://dx.doi.org/10.1055/s-2007-971173,0,0,
2050,Inherited metabolic disease of the liver,"PURPOSE OF REVIEW: The past decade has seen extraordinary growth in our understanding of the pathophysiology of Wilson disease, genetic hemochromatosis and alpha-1 antitrypsin deficiency as we continue to elucidate the molecular and cellular machinery involved in their pathogenesis. The continued progress in the elaboration of the molecular biology, genetics, epidemiology, and management of these prototypical inherited metabolic diseases will be the focus of this review. RECENT FINDINGS: Wilson disease and genetic hemochromatosis involve defects in metal transport with copper and iron accumulation in hepatocytes, respectively. In alpha-1 antitrypsin deficiency, hepatocytes accumulate defective alpha-1 antitrypsin that misfolds. As a more complete picture of the molecular biology of the proteins and genes involved in transport has evolved, so has our understanding of the etiopathogenesis of these disorders and the variety of phenotypes observed. Finally, new ideas regarding the clinical management of these disorders will emerge with elucidation of the cellular basis for these diseases. SUMMARY: The recent developments detailed in this article have important implications for the future diagnosis and treatment of these diseases. Recent discoveries link molecular defects with alterations in the functional machinery of the cell, and provide new avenues for advancing the diagnosis and treatment of these disorders. © 2007 Lippincott Williams & Wilkins, Inc.",alpha-1 antitrypsin;Ceruloplasmin;Hemochromatosis;Hepcidin;Iron;Wilson disease;alpha 1 antitrypsin deficiency/ep [Epidemiology];alpha 1 antitrypsin deficiency/et [Etiology];apoptosis;chelation therapy;clinical trial;diagnostic test;drug substitution;drug withdrawal;enzyme linked immunosorbent assay;epidemiological data;gene mutation;gene therapy;hemochromatosis/et [Etiology];hepatocyte transplantation;human;immunosuppressive treatment;kidney disease/co [Complication];kidney disease/dt [Drug Therapy];liver disease;liver graft rejection/dt [Drug Therapy];liver transplantation;metabolic disorder;molecular biology;molecular genetics;nonhuman;review;seizure/dt [Drug Therapy];treatment planning;viral gene delivery system;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alpha 1 antitrypsin/ec [Endogenous Compound];cyclosporin/dt [Drug Therapy];indometacin/to [Drug Toxicity];iron binding protein;lentivirus vector/pr [Pharmaceutics];nonsteroid antiinflammatory agent;rapamycin/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dt [Drug Therapy];transferrin receptor;trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];Wilson disease protein/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Fink, S.;Schilsky, M. L.",2007,May,http://dx.doi.org/10.1097/MOG.0b013e3280ef68e4,0,0,
2051,Gastrointestinal medications in pregnancy,"Management of the pregnant patient presents unique challenges to the treating physician. Current Food and Drug Administration classifications do not necessarily reflect clinical experience or recent literature. Ideally, one should use the lowest-risk drug possible, with attention to the appropriate level of efficacy for the patient's condition, the stage of pregnancy and dose adjustment. Every treatment decision should be fully discussed with the patient and a multidisciplinary team that should include the obstetrician and, if appropriate, the paediatrician. This review will cover the medications commonly used to treat gastrointestinal disease. The majority of medications can be categorised as 'low risk' or 'should be avoided'. The following medications should never be used during pregnancy due to the clear risk of teratogenicity or adverse events: bismuth, castor oil, sodium bicarbonate, methotrexate, ribavirin, doxycycline, tetracycline, and thalidomide. © 2007 Elsevier Ltd. All rights reserved.",endoscopy;gastrointestinal;irritable bowel syndrome;medications;pregnancy;acute pancreatitis/dt [Drug Therapy];article;biliary tract disease/dt [Drug Therapy];biliary tract disease/su [Surgery];cholangitis/si [Side Effect];chronic pancreatitis/dt [Drug Therapy];clinical protocol;clinical trial;common bile duct stone/dt [Drug Therapy];common bile duct stone/su [Surgery];constipation/dt [Drug Therapy];diarrhea/dt [Drug Therapy];drug bioavailability;drug blood level;drug dose titration;drug excretion;food and drug administration;gastroesophageal reflux/dt [Drug Therapy];gastrointestinal disease/dt [Drug Therapy];gastrointestinal endoscopy;hemostasis;hepatitis/dt [Drug Therapy];human;hypoglycemia/dt [Drug Therapy];hypotension/si [Side Effect];irritable colon/dt [Drug Therapy];liver transplantation;medical decision making;nausea and vomiting/dt [Drug Therapy];nonhuman;peptic ulcer/dt [Drug Therapy];portal hypertension/dt [Drug Therapy];primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/dt [Drug Therapy];respiration depression/si [Side Effect];risk assessment;teratogenicity;Wilson disease/dt [Drug Therapy];adrenalin/to [Drug Toxicity];ampicillin/dt [Drug Therapy];antacid agent/dt [Drug Therapy];antacid agent/to [Drug Toxicity];antibiotic agent/ct [Clinical Trial];antibiotic agent/dt [Drug Therapy];antibiotic agent/iv [Intravenous Drug Administration];antidepressant agent/dt [Drug Therapy];antidepressant agent/to [Drug Toxicity];bicarbonate/dt [Drug Therapy];bicarbonate/to [Drug Toxicity];bismuth/dt [Drug Therapy];bismuth/to [Drug Toxicity];castor oil/dt [Drug Therapy];castor oil/to [Drug Toxicity];chenodeoxycholic acid/dt [Drug Therapy];chenodeoxycholic acid/po [Oral Drug Administration];contrast medium/ae [Adverse Drug Reaction];contrast medium/to [Drug Toxicity];diazepam/to [Drug Toxicity];doxycycline/dt [Drug Therapy];doxycycline/to [Drug Toxicity];flumazenil/pd [Pharmacology];gastrointestinal agent/dt [Drug Therapy];glucagon/dt [Drug Therapy];glucagon/pd [Pharmacology];lamivudine/dt [Drug Therapy];lamivudine/to [Drug Toxicity];methotrexate/dt [Drug Therapy];methotrexate/to [Drug Toxicity];metoclopramide/dt [Drug Therapy];metoclopramide/to [Drug Toxicity];midazolam/ad [Drug Administration];midazolam/cr [Drug Concentration];midazolam/im [Intramuscular Drug Administration];midazolam/iv [Intravenous Drug Administration];midazolam/po [Oral Drug Administration];midazolam/pk [Pharmacokinetics];naloxone/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];pethidine/cr [Drug Concentration];pethidine/to [Drug Toxicity];pethidine/iv [Intravenous Drug Administration];pethidine/pk [Pharmacokinetics];propranolol/dt [Drug Therapy];propranolol/to [Drug Toxicity];proton pump inhibitor/dt [Drug Therapy];ribavirin/dt [Drug Therapy];ribavirin/to [Drug Toxicity];simethicone;tetracycline/dt [Drug Therapy];tetracycline/to [Drug Toxicity];thalidomide/dt [Drug Therapy];thalidomide/to [Drug Toxicity];unindexed drug;ursodeoxycholic acid/ct [Clinical Trial];ursodeoxycholic acid/dt [Drug Therapy];ursodeoxycholic acid/to [Drug Toxicity],"Mahadevan, U.",2007,October,http://dx.doi.org/10.1016/j.bpg.2007.06.002,0,0,
2052,Biological applications of X-ray fluorescence microscopy: exploring the subcellular topography and speciation of transition metals,"Synchrotron X-ray fluorescence microscopy (SXRF) is a microanalytical technique for the quantitative mapping of elemental distributions. Among currently available imaging modalities, SXRF is the only technique that is compatible with fully hydrated biological samples such as whole cells or tissue sections, while simultaneously offering trace element sensitivity and submicron spatial resolution. Combined with the ability to provide information regarding the oxidation state and coordination environment of metal cations, SXRF is ideally suited to study the intracellular distribution and speciation of trace elements, toxic heavy metals and therapeutic or diagnostic metal complexes. © 2007 Elsevier Ltd. All rights reserved.",Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/et [Etiology];brain tissue;cellular distribution;degenerative disease/et [Etiology];diagnostic imaging;drug absorption;drug metabolism;Escherichia coli;fluorescence microscopy;human;infection/et [Etiology];intoxication/et [Etiology];nerve cell;nonhuman;Parkinson disease/et [Etiology];phytoplankton;Pseudomonas fluorescens;review;tissue section;whole cell;Wilson disease/et [Etiology];X ray fluorescence;antineoplastic agent;chromium/to [Drug Toxicity];cisplatin/pk [Pharmacokinetics];cisplatin/pd [Pharmacology];copper/ec [Endogenous Compound];heavy metal;iron/ec [Endogenous Compound];metal ion;transition element;zinc/ec [Endogenous Compound],"Fahrni, C. J.",2007,April,http://dx.doi.org/10.1016/j.cbpa.2007.02.039,0,0,
2053,"Copper and human health: Biochemistry, genetics, and strategies for modeling dose-response relationships","Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation (including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency. Copyright © Taylor & Francis Group, LLC.",acute toxicity;biliary excretion;cell membrane transport;chronic toxicity;clinical feature;copper deficiency/di [Diagnosis];copper metabolism;cytotoxicity;data base;developmental disorder;dietary intake;disease course;dose response;embryo development;fetus development;gene deletion;gene mutation;homeostasis;human;idiopathic copper toxicosis/et [Etiology];inborn error of metabolism;Indian childhood cirrhosis/et [Etiology];intestine absorption;laboratory test;malformation syndrome;Menkes syndrome/di [Diagnosis];Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];missense mutation;molecular dynamics;nonhuman;nutritional deficiency;oxidative stress;prognosis;regression analysis;reproductive toxicity;review;screening test;single nucleotide polymorphism;statistical model;stomach absorption;teratogenicity;tissue distribution;toxicity testing;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine triphosphatase;cadmium;carrier protein/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chaperone/ec [Endogenous Compound];chopper chaperone for superoxide dismutase;copper/to [Drug Toxicity];copper derivative/dt [Drug Therapy];copper exporting adenosine triphosphatase/ec [Endogenous Compound];histidine copper/dt [Drug Therapy];histidine copper/ip [Intraperitoneal Drug Administration];histidine copper/tl [Intrathecal Drug Administration];iron;Menkes protein/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];nuclear Menkes like protein;penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];protein;protein Atox1;protein cox11;protein COX17;protein Sco1;protein Sco2;tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc;zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Stern, B. R.;Solioz, M.;Krewski, D.;Aggett, P.;Aw, T. C.;Baker, S.;Crump, K.;Dourson, M.;Haber, L.;Hertzberg, R.;Keen, C.;Meek, B.;Rudenko, L.;Schoeny, R.;Slob, W.;Starr, T.",2007,April/May,http://dx.doi.org/10.1080/10937400600755911,0,0,
2054,Treatment of iron storage disease. [Spanish],,chronic hepatitis;conference paper;hematology;heredity;human;liver disease;Wilson disease;penicillamine,"Quintero Carrion, E.;Pardo Balteiro, A.",2007,21 Feb,,0,0,
2055,Dermato-venereological quiz,,adult;article;case report;cheek;chin;cryotherapy;curettage;differential diagnosis;discoid lupus erythematosus;disease association;elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/su [Surgery];elastosis perforans serpiginosa/th [Therapy];elbow;face;fungus culture;granuloma;granuloma annulare;histopathologic skin reaction/di [Diagnosis];histopathologic skin reaction/dt [Drug Therapy];histopathologic skin reaction/su [Surgery];histopathologic skin reaction/th [Therapy];human;human tissue;immunofluorescence;knee;laser;male;neck;papule;porokeratosis;prognosis;prurigo;skin biopsy;skin defect;tinea corporis;Wilson disease/dt [Drug Therapy];keratolytic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];steroid/tp [Topical Drug Administration],"Yeung, K. H.;Jong, K. K.",2007,Winter,,0,0,
2056,Wilson's disease,,cataract;chelation;cornea;genetics;human;kidney disease;knowledge;letter;liver;osteoarthropathy;priority journal;symptom;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Walshe, J.",2007,17 Mar,http://dx.doi.org/10.1016/S0140-6736%2807%2960438-3,0,0,
2057,Ocular signs of genetic disease - Case 1: Wilson disease,,adult;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;autosomal recessive inheritance;case report;clinical assessment;clinical feature;comorbidity;copper blood level;data base;disease association;eye disease/di [Diagnosis];eye disease/et [Etiology];eye examination;gene deletion;gene mutation;genetic disorder;high risk patient;human;incidence;kayser fleischer/di [Diagnosis];kayser fleischer/et [Etiology];liver cirrhosis;male;priority journal;risk factor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper exporting adenosine triphosphatase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];polypeptide/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Wilson, G. N.",2007,July,,0,0,
2058,Three atypical cases of Wilson disease: Assessment of the Leipzig scoring system in making a diagnosis,"Background/Aims: The diagnosis of this condition in the absence of any neurological findings may pose a dilemma. In 2001, experts from The 8th International Conference on Wilson disease (WD) and Menkes disease in Leipzig, Germany proposed a scoring system that may facilitate diagnosis of WD. Methods/Results: Three patients were identified as having an atypical presentation of WD as they all presented after the age 40. Two of the three presented with established cirrhosis, and none had any neuropsychiatric manifestations. All three patients fulfilled the Leipzig diagnostic criteria proposed by EASL prior to confirmatory mutation analysis. Patient A died of liver failure despite treatment. Patients B and C have remained with stable liver disease on chelation therapy. Conclusions: We believe these patients represent a group most likely to be missed in the diagnostic work-up of liver disease due to a combination of atypical features such as older age of onset, presence of other confounders for liver disease, and sometimes absence of Kayser-Fleischer rings. The Leipzig scoring system proposed in 2003 was helpful in support of an initial diagnosis of Wilson disease in these patients, validated later by genetic testing. © 2007 European Association for the Study of the Liver.",Atypical Leipzig;Score Mutation Analysis;Wilson Disease;abdominal pain;add on therapy;adult;alanine aminotransferase blood level;analytic method;article;bilirubin blood level;case report;chelation therapy;diarrhea;drug substitution;drug withdrawal;eye pain/si [Side Effect];fatigue/si [Side Effect];female;genetic analysis;hair loss/si [Side Effect];human;liver biopsy;liver cirrhosis;liver disease;liver failure;nausea/si [Side Effect];nuclear magnetic resonance imaging;patient compliance;priority journal;proteinuria/si [Side Effect];rectum hemorrhage;scoring system;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Xuan, A.;Bookman, I.;Cox, D. W.;Heathcote, J.",2007,September,http://dx.doi.org/10.1016/j.jhep.2007.05.016,0,0,
2059,Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide,"Wilson disease is caused by accumulation of Cu<sup>2+</sup> in cells, which results in liver cirrhosis and, occasionally, anemia. Here, we show that Cu<sup>2+</sup> triggers hepatocyte apoptosis through activation of acid sphingomyelinase (Asm) and release of ceramide. Genetic deficiency or pharmacological inhibition of Asm prevented Cu<sup>2+</sup>-induced hepatocyte apoptosis and protected rats, genetically prone to develop Wilson disease, from acute hepatocyte death, liver failure and early death. Cu<sup>2+</sup> induced the secretion of activated Asm from leukocytes, leading to ceramide release in and phosphatidylserine exposure on erythrocytes, events also prevented by inhibition of Asm. Phosphatidylserine exposure resulted in immediate clearance of affected erythrocytes from the blood in mice. Accordingly, individuals with Wilson disease showed elevated plasma levels of Asm, and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes. Our data suggest a previously unidentified mechanism for liver cirrhosis and anemia in Wilson disease. © 2007 Nature Publishing Group.",adult;anemia;animal cell;apoptosis;article;blood level;cell death;controlled study;drug activation;drug inhibition;erythrocyte;female;human;leukocyte;liver cell;liver cirrhosis;liver failure;mouse;nonhuman;priority journal;protein deficiency/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];amitriptyline/dt [Drug Therapy];amitriptyline/ip [Intraperitoneal Drug Administration];ceramide;copper;penicillamine/dt [Drug Therapy];phosphatidylserine;sphingomyelin phosphodiesterase/pd [Pharmacology];trientine/dt [Drug Therapy],"Lang, P. A.;Schenck, M.;Nicolay, J. P.;Becker, J. U.;Kempe, D. S.;Lupescu, A.;Koka, S.;Eisele, K.;Klarl, B. A.;Rubben, H.;Schmid, K. W.;Mann, K.;Hildenbrand, S.;Hefter, H.;Huber, S. M.;Wieder, T.;Erhardt, A.;Haussinger, D.;Gulbins, E.;Lang, F.",2007,February,http://dx.doi.org/10.1038/nm1539,0,0,
2060,Coexistence of Wilson's disease and neurofibromatosis type 1 in a 14-year-old boy [11],,adolescent;anamnesis;blood analysis;case report;diagnostic procedure;grand mal epilepsy;human;hydrocephalus;laboratory test;letter;male;neurofibromatosis/di [Diagnosis];neurofibromatosis/dt [Drug Therapy];nuclear magnetic resonance imaging;parkinsonism/dt [Drug Therapy];physical examination;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Sahraian, M.;Motamedi, M.;Paknejad, S. M.;Azimi, A.",2007,01 Jan,,0,0,
2061,The onset of psychiatric disorders and Wilson's disease. [French],"Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric disease in at least 90% of the patients. In some rare cases, the first manifestations of the disease can be psychiatric which, according to the literature, accounts for only 10% of the cases. The disease can be revealed by isolated behavioral problems, an irrational syndrome, a schizophrenic syndrome, or a manic-depressive syndrome. Damage to the central nervous system can be more severe, thus, several differential diagnoses have been discussed:*a psychotic disorder of late appearance;*a depressive state;*a mental confusion disorder. The clinical syndrome is complex. Indeed, it is the polymorphism, which dominates in the description of the psychiatric demonstrations of the disease. This can lead to prejudicial diagnostic wandering, particularly since heavy sedative treatment may be required to suppress behavioral problems. Clinically, Wilson's disease generally appears between the age of 10 and 20. It rarely remains masked until after the age of 40. The first manifestations are hepatic (40% of the cases), neurological (35%) or psychiatric (10%). The inaugural disorder can finally take on a haematological, renal, or mixed form in approximately 15% of the cases. We have detailed the principal clinical elements. In approximately 40-50% of the patients, the first manifestation of the disease affects the central nervous system, where it can cause either a progressive neurological disease, or psychiatric disorders. The ophthalmologic disorder is dominated by Kayser-Fleischer's ring, representing a green or bronze colored ring on the periphery of the cornea. It occupies the higher pole of the cornea, then the lower pole, and extends to the whole circumference. It is generally only visible under examination with a slit lamp. It disappears on average within 3-5 years following copper chelating therapy. Kayser-Fleischer's ring has been described other than in Wilson's disease, in exceptional cases of prolonged cholestasis. On haematological level, the hyperhaemolysis is due to the toxicity of the ionic copper, released massively in the plasma by hepatocellular necrosis. he other manifestations can be found in the following organs: renal, osteoarticular, cardiac, endocrine, cutaneous, and in the teguments. Until 1952, the diagnosis was evoked only on clinical symptomatology. It can henceforth be marked unambiguous, even in the absence of any symptom, by the description of a ceruloplasmin plasma concentration of less than 200 ml/l, and of a Kayser-Fleischer's ring. Hepatic copper on sample is constantly increased during the disease (from 3 to 25 mumol/g of dry weight). On the other hand, the absence of a reduction in the plasma ceruloplasmin does not make it possible to exclude the diagnosis. Conversely, a reduction in ceruloplasmin can exist other than in Wilson's disease (nephritic syndrome, malabsorption syndrome, or severe hepatic insufficiency). Kayser-Fleischer's ring is quasiconstant among patients with neuropsychiatric demonstrations (thus, its absence represents a very strong argument against the diagnosis). It can on the other hand be lacking during hepatic forms, and in this case, its absence is not an argument against the diagnosis. Magnetic resonance imaging can reveal abnormal signals of the grey cores. A genetic study is conducted by liaison analysis in the event of a family history of the disease. When it is not treated, Wilson's disease induces lesions of the tissues, the outcome of which is always fatal. Treatment relies on the regulation of copper chelation, which improves the prognosis, and zinc, which captures the copper in a nontoxic form. The severe psychiatric disorders observed during Wilson's disease may require tranquilizers, but care should be taken because of potential neurological or hepatic side effects. Lithium seems an interesting treatment and remains theoretically indicated, taking into account the scarcity of the extrapyramidal symptoms and the hepatic dysfunction among patients at the stage of cirrhosis, since it is not metabolized in the liver. Although rare, it is important to approach Wilson's disease in psychiatry because the psychiatric manifestations can precede the somatic disorders and help to pose the diagnosis. We stress the importance of the early diagnosis of the pathology, the outcome of which is fatal in the absence of specific treatment. © 2007 L'Encephale, Paris, 2007.",Autosomal recessive;Ceruloplasmin;Kayser-Fleischer's ring;Polymorphous psychotic disorder;Treatment for life;Wilson's disease;acute hepatitis;article;biliary excretion;central nervous system;chelation therapy;chromosome 13;clinical feature;controlled study;eye disease;heterozygote;homozygote;human;liver biopsy;liver cirrhosis;liver failure;liver injury;liver toxicity/si [Side Effect];liver transplantation;mental disease/co [Complication];mental disease/dt [Drug Therapy];nuclear magnetic resonance imaging;protein synthesis;recessive gene;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];copper;copper ion/ec [Endogenous Compound];lithium/dt [Drug Therapy];tranquilizer/ae [Adverse Drug Reaction];tranquilizer/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc,"Benhamla, T.;Tirouche, Y. D.;Abaoub-Germain, A.;Theodore, F.",2007,December,http://dx.doi.org/10.1016/j.encep.2006.08.009,0,0,
2062,WILSON'S disease in childhood and adolescent. Diagnosis and treatment. [German],"The first essential in making the diagnosis of WILSON'S disease is to think of it. Neurologists do a better job in this respect in comparison to pediatricians. The main clinical presentation in children refers to the liver, acute hemolysis may occur in addition. Neurological manifestations can be seen normally in adolescents only. The diagnosis is based on low serum levels of ceruloplasmin and copper, increased serum transaminases, elevated copper excretion in 24-h-urine and increased copper content of the liver tissue. However, pitfalls in this diagnostic puzzle may occur. Haplotype analysis allow the diagnosis in presymptomatic siblings of an index patient. Lifelong treatment with chelators as penicillamine or trientine is mandatory, zinc is an alternative in presymptomatic cases and after several years of copper detoxification with penicillamine. Acute liver failure and decompensated liver cirrhosis are indications for liver transplantation.",Chelator treatment;Hemolysis;Liver cirrhosis;Wilson's disease;Zinc;adolescent;article;blood analysis;child;clinical feature;detoxification;diagnostic procedure;haplotype;human;liver cirrhosis/co [Complication];liver cirrhosis/su [Surgery];liver disease;liver failure/co [Complication];liver failure/su [Surgery];liver transplantation;neurologic disease;patient care;patient compliance;prognosis;sibling;symptom;treatment indication;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Keller, K. M.",2007,December,,0,0,
2063,The LEC rat: A useful model for studying liver carcinogenesis related to oxidative stress and inflammation,"Growing evidence indicates oxidative stress as a mechanism of several diseases including cancer. Oxidative stress can be defined as the imbalance between cellular oxidant species production and antioxidant capability shifted towards the former. Lipid peroxidation is one of the processes that takes place during oxidative stress. Lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), are closely related to carcinogenesis as they are potent mutagens and they have been suggested as modulators of signal pathways related to proliferation and apoptosis, two processes implicated in cancer development. Mechanisms by which oxidative stress leads to tumor formation are still under investigation. The need of suitable in vivo models that could reflect that inflammation-related human carcinogenesis is evident. In this regard, the mutant strain Long Evans Cinnamon-like (LEC) rat provides a promising model for investigation of the relationship between hepatitis induced by oxidative stress and hepatocarcinogenesis because it has been demonstrated to develop spontaneous liver tumor formation related to copper accumulation and oxidative stress. In this review, the findings regarding oxidative stress and its relation with liver pathologies in LEC rats are discussed; we focus on the mechanisms proposed for HNE carcinogenesis. © W. S. Maney & Son Ltd.",Hepatocarcinogenesis;hne;LEC rat;Oxidative stress;antineoplastic activity;cancer model;cancer prevention;clinical feature;conference paper;copper blood level;copper metabolism;disease association;drug mechanism;hepatitis/dt [Drug Therapy];hepatitis/pc [Prevention];histopathology;human;jaundice/dt [Drug Therapy];lipid peroxidation;liver cancer/dt [Drug Therapy];liver cancer/et [Etiology];liver cancer/pc [Prevention];liver carcinogenesis;liver cell carcinoma/dt [Drug Therapy];liver cell carcinoma/et [Etiology];liver cell carcinoma/pc [Prevention];liver failure/dt [Drug Therapy];liver failure/pc [Prevention];liver injury;liver tumor;Long Evans cinnamon rat;nonhuman;priority journal;rat strain;sex difference;strain difference;Wilson disease;4 hydroxynonenal/ec [Endogenous Compound];acetylcysteine/cb [Drug Combination];acetylcysteine/dt [Drug Therapy];antioxidant/dt [Drug Therapy];ascorbic acid/cb [Drug Combination];ascorbic acid/dt [Drug Therapy];carnitine/pd [Pharmacology];copper/ec [Endogenous Compound];curcumin/dt [Drug Therapy];iron/ec [Endogenous Compound];malonaldehyde/ec [Endogenous Compound];n benzylglucamine n carbodithioic acid/dt [Drug Therapy];n benzylglucamine n carbodithioic acid/pd [Pharmacology];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];proline/cb [Drug Combination];proline/dt [Drug Therapy];quercetin/dt [Drug Therapy];thioctic acid/pd [Pharmacology];thioredoxin/cb [Drug Combination];thioredoxin/dt [Drug Therapy];trientine/dt [Drug Therapy];trientine/pd [Pharmacology],"Marquez, A.;Villa-Trevino, S.;Gueraud, F.",2007,February,http://dx.doi.org/10.1179/135100007X162220,0,0,
2064,Treatable hereditary neuro-metabolic diseases. [French],"Hereditary metabolic diseases may appear during adolescence or young adulthood, revealed by an apparently unexplained neurological or psychiatric disorder. Certain metabolic diseases respond to specific treatments and should be identified early, particularly in emergency situations where rapid introduction of a treatment can avoid fatal outcome or irreversible neurological damage. The main diseases leading to an acute neurological syndrome in the adult are urea cycle disorders, homocysteine metabolisms disorders and porphyria. More rarely, Wilson's disease, aminoacid diseases, organic aciduria, or pyruvate dehydrogenase deficiency, beta-oxidation disordes or biotin metabolism may be involved. Most emergency situations can be screen correctly with simple tests (serum ammonia, homocysteine, lactate, urinary prophyrines, acylcarnitine pattern, amino acid and organic acid chromatography). For chronic situations, the main treatable diseases are Wilson's disease, homocysteine, cerebrotendinous xanthomatosis, Refsum's disease, vitamin E deficiency, Gaucher's disease, Fabry's disease, and neurotransmitter metabolism disorders. We present treatable metabolic disorders as a function of the different clinical situations observed in adults. © 2007. Elsevier Masson SAS.",Adults;Hereditary metabolic diseases;Inborn metabolism errors;Leucodystrophy;Neurology;Treatment;aciduria;alpha tocopherol deficiency;ammonia blood level;anorexia/si [Side Effect];cerebrovascular accident;chromatography;diarrhea/si [Side Effect];dyskinesia/si [Side Effect];epilepsy;Fabry disease;fatty acid oxidation;Gaucher disease;human;inborn error of metabolism/dt [Drug Therapy];laboratory test;metabolic disorder;metabolic encephalopathy;nausea/si [Side Effect];neurologic disease;porphyria;psychiatry;Refsum disease;review;screening test;tachycardia/si [Side Effect];urea cycle;Wilson disease;5 hydroxytryptophan/ae [Adverse Drug Reaction];5 hydroxytryptophan/dt [Drug Therapy];5 hydroxytryptophan/po [Oral Drug Administration];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/iv [Intravenous Drug Administration];agalsidase beta/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];alpha tocopherol/po [Oral Drug Administration];arginine/dt [Drug Therapy];arginine/iv [Intravenous Drug Administration];arginine/po [Oral Drug Administration];benzoic acid/dt [Drug Therapy];benzoic acid/iv [Intravenous Drug Administration];benzoic acid/po [Oral Drug Administration];betaine/dt [Drug Therapy];betaine/po [Oral Drug Administration];biotin/dt [Drug Therapy];biotin/po [Oral Drug Administration];carglumic acid/dt [Drug Therapy];carglumic acid/iv [Intravenous Drug Administration];carglumic acid/po [Oral Drug Administration];carnitine/po [Oral Drug Administration];chenodeoxycholic acid/dt [Drug Therapy];chenodeoxycholic acid/po [Oral Drug Administration];citrulline/dt [Drug Therapy];citrulline/po [Oral Drug Administration];cyanocobalamin/dt [Drug Therapy];cyanocobalamin/im [Intramuscular Drug Administration];cyanocobalamin/po [Oral Drug Administration];dextromethorphan/dt [Drug Therapy];dextromethorphan/po [Oral Drug Administration];folic acid/dt [Drug Therapy];folic acid/po [Oral Drug Administration];imiglucerase/dt [Drug Therapy];imiglucerase/iv [Intravenous Drug Administration];ketamine/dt [Drug Therapy];ketamine/po [Oral Drug Administration];levodopa/ae [Adverse Drug Reaction];levodopa/dt [Drug Therapy];levodopa/po [Oral Drug Administration];miglustat/dt [Drug Therapy];miglustat/po [Oral Drug Administration];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];pyridoxine/dt [Drug Therapy];pyridoxine/po [Oral Drug Administration];serine/dt [Drug Therapy];serine/po [Oral Drug Administration];thiamine/dt [Drug Therapy];thiamine/po [Oral Drug Administration];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];ubiquinone/dt [Drug Therapy];ubiquinone/po [Oral Drug Administration];zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration],"Sedel, F.;Lyon-Caen, O.;Saudubray, J. M.",2007,October,http://dx.doi.org/10.1016/S0035-3787%2807%2992631-4,0,0,
2065,Effect of penicillamine and zinc on iron metabolism in Wilson's disease,"Objective. The physiology of iron metabolism in Wilson's disease is largely unknown, and there is a paucity of data on the real presence and progression of iron accumulation. The purpose of this study was to assess the iron metabolism parameters, including hepatic iron concentration, in follow-up liver biopsies and serum, and urinary pro-hepcidin. Material and methods. Twenty-three Wilson's disease patients undergoing long-term treatment were enrolled in the study. Results. Hepatic iron content was significantly increased in penicillamine-treated patients compared with zinc-treated patients. Serum and urinary pro-hepcidin concentrations were significantly higher in Wilson's disease patients than in healthy volunteers, despite a normal biochemical pattern of iron metabolism. Conclusions. Long-term penicillamine treatment seems to be responsible for a more marked iron accumulation in the liver. This observation may justify a revision of long-term Wilson's disease treatment modalities with penicillamine. The finding that serum and urinary pro-hepcidin is significantly increased in Wilson's disease patients compared with healthy volunteers suggests a role for hepcidin in iron metabolism in Wilson's disease, but this needs to be confirmed by a study of hepatic hepcidin expression in these patients. © 2007 Taylor & Francis.",Copper;Hepcidin;Iron;Wilson's disease;adult;analytic method;article;chemical analysis;clinical article;comparative study;concentration (parameters);controlled study;female;follow up;human;iron metabolism;liver biopsy;male;priority journal;volunteer;Wilson disease/dt [Drug Therapy];hepcidin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Medici, V.;Leo, V. D.;Lamboglia, F.;Bowlus, C. L.;Tseng, S. C.;D'Inca, R.;Irato, P.;Burra, P.;Martines, D.;Sturniolo, G. C.",2007,,http://dx.doi.org/10.1080/00365520701514495,0,0,
2066,Wilson's disease in two consecutive generations in a Bulgarian Roma family [9],,adult;case report;child;DNA isolation;DNA sequence;family history;female;hepatomegaly;heterozygosity;human;laboratory test;letter;male;neurologic examination;priority journal;wild type;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Mihaylova, V.;Todorov, T.;Jelev, H.;Cherninkova, S.;Raycheva, M.;Savov, A.;Kremensky, I.;Tournev, I.",2007,October,http://dx.doi.org/10.1007/s00415-007-0564-1,0,0,
2067,Carotid dissection after long-term treatment with D-penicillamine in Wilson's disease. [German],,adult;aphasia;carotid artery injury;case report;disease course;dysarthria;human;internal carotid artery aneurysm;nuclear magnetic resonance imaging;recanalization;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy],"Gunther, P.;Hermann, W.;Kuhn, H. J.;Schneider, J. P.;Wagner, A.",2007,,,0,0,
2068,Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation,"Wilson's disease (WD) is a rare autosomal-recessive disorder of copper metabolism with predominantly hepatic and extrapyramidal motor symptoms. Copper chelating therapy has proven to be an effective treatment for WD. Yet, if conservative treatment fails, liver transplantation (LT) often is the only remaining therapeutic option. The indication for LT especially in patients with stable liver function but severe neurological manifestation is debated controversially. In this case report, we document the follow up of neurological symptoms in WD after LT for the first time on video. © 2007 Movement Disorder Society.",Liver transplantation;Morbus Wilson;Video documentation;adult;article;autosomal recessive disorder;case report;clinical feature;copper metabolism;disease severity;follow up;human;male;motor dysfunction;myoclonus/si [Side Effect];priority journal;symptom;tremor/si [Side Effect];videorecording;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Suess, T.;Bokemeyer, M.;Schomerus, G.;Donnerstag, F.;Manns, M. P.;Klempnauer, J.;Kolbe, H.;Weissenborn, K.",2007,15 May,http://dx.doi.org/10.1002/mds.21444,0,0,
2069,Whipple's triad as a clinical manifestation of hepatolenticular degeneration. [Polish],"Hepatolenticular degeneration (Wilson's disease) is a rare condition characterised by a defect in biliary excretion of copper resulting in excessive copper accumulation and toxicity. To the most frequent symptoms of this disorder belong liver, neurological or psychiatric disturbances, although other less common clinical features may sometimes be present. Since the clinical presentation of the disease is highly heterogeneous, it may mimic the symptoms of many various disorders. Diagnosis of the condition depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Early detection and treatment protect patients from devastating organ damage. We describe an atypical case of Wilson's disease in a 23-year-old woman, whose clinical presentation suggested the presence of an insulin-secreting tumour. After the diagnosis was established and zinc sulphate treatment implemented, her clinical status improved remarkably. The presented case suggests that hepatolenticular degeneration should be taken into consideration in a differential diagnosis of hypoglycaemia of an unknown origin. Copyright by Medycyna Praktyczna, 2007.",Clinical presentation;Diagnosis;Hypoglycaemia;Insulinoma;Wilson's disease;adult;article;bile;biliary excretion;case report;clinical feature;diagnostic procedure;differential diagnosis;female;human;hypoglycemia/di [Diagnosis];intestine lipodystrophy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Krysiak, R.;Okopien, B.",2007,,,0,0,
2070,Wilson's disease in patients with mental disorders. [German],"Wilson's disease is a hereditary autosomal-recessive disorder of copper metabolism caused by a defect of a copper-transporting ATPase, which binds copper to apoceruloplasmin facilitating excretion of copper into the bile. The result is an accumulation of copper in multiple organs. The resulting clinical syndrome is primarily characterized by liver-dysfunction. However, neurologic and psychiatric symptoms are common and may be the first clinical manifestations. Though Wilson's disease is infrequent, psychiatrists should be aware of this diagnosis since - treated early - the prognosis is favourable, and persistent organ damage or letal outcomes can often be avoided. Wilson's disease appears to be an important differential diagnosis particularly in younger patients presenting psychiatric symptoms for the first time. For screening purposes measuring of ceruloplasmin and copper in serum seems to be adequate. © 2007 Schattauer GmbH.",Ceruloplasmin;Copper metabolism;Mental disorders;Wilson's disease;autosomal recessive disorder;copper blood level;differential diagnosis;genetic analysis;human;liver biopsy;liver cirrhosis;mental disease;review;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/dt [Drug Therapy],"Bux, C. J.;Rosenbohm, A.;Connemann, B. J.",2007,,,0,0,
2071,Wilson disease: an update. [Korean],"Wilson disease (WD) is an autosomal recessive disorder of copper transport that results in accumulation of copper primarily in the liver, the brain and the cornea. WD is the most common inherited liver disease with the prevalence of 1: 37,000 in the pediatric population in Korea. Mutations in the ATP7B gene cause failure of copper excretion into the bile and a defective incorporation of copper into ceruloplasmin. More than 300 mutations in the ATP7B gene have been described so far. Mutations differ between ethnic groups. The p.R778L (an allele frequency of 37%), p.A874V (13%), p.L1083F (8%) and p.N1270S (6%) are the common major mutations in Korea. Conflicting results on genotype/phenotype correlations of the most common mutations have been reported in various countries. There seems to be no correlation between the R778L mutation and age of onset or clinical manifestations in Korean patients. None of the laboratory parameters alone allows a definite diagnosis of WD. In a nation-wide survey of WD, low serum ceruloplasmin (<20 mg/dL), high 24 hour urine copper (>100 microgram), high hepatic copper content (>250 microgram/g of dry liver) and Kayser-Fleischer rings were found in 96%, 86%, 88%, and 73% of the 550 Korean patients respectively. A combination of any two of the above 4 laboratory findings is strong support for a diagnosis of WD. For the last couple of years, genetic testing has been playing an increasingly important role in diagnosing WD. Direct DNA sequencing did confirm WD in 98% of the Korean patients. Two mutations were detected in 70% and one mutation in 28% of the patients who showed characteristic biochemical and clinical findings of WD. Genetic testing, either by haplotype analysis or by mutation analysis, is the only reliable tool for differentiating heterozygote carriers from affected asymptomatic patients. The agents of the first choice among chelators and zinc in specific clinical situations of WD is still a matter of debate. Because of frequent side effects and initial neurologic deterioration of penicillamine therapy, less toxic trientine or zinc has gradually replaced penicillamine over the past few years. Trientine or tetrathiomolybdate has been increasingly recommended as the first-line treatment for neurologic WD. Currently, liver transplantation is not recommended as primary treatment for neurologic WD. Recently published data show that initial zinc therapy for asymptomatic/presymptomatic patients and maintenance zinc therapy in patients after long term chelation are safe and effective. Further researches and the new guidelines on the proper management of patients with WD are needed.",differential diagnosis;genetic screening;genetics;human;liver;metabolism;mutation;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adenosine triphosphatase;cation transport protein;copper;penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy];trientine/ad [Drug Administration];trientine/dt [Drug Therapy];Wilson disease protein;zinc/ad [Drug Administration];zinc/dt [Drug Therapy],"Seo, J. K.",2006,Sep,,0,0,
2072,Reversible dementias and treatable dementias. [Spanish],"Introduction. When studying patients with dementia the search of reversible or treatable entities has a primordial role. Many patients do not recover the previous cognitive level; however, that does not signify that the disease is not treatable with partial recovery or prevention of secondary progression. Development. The prevalence of reversible dementias is around 15% in most series. Rutine studies include complete blood cell count, erythrocyte sedimentation rate, electrolytes and chemistry panel, liver function tests, vitamin B<inf>12</inf> and folate serum levels, urianalysis and syphilis serology. Special tests such as thyroid function tests, protein electrophoresis, human immunodeficiency virus serology, heavy metals serum levels, electrocardiography, cerebrospinal fluid analysis, and chest roentnography should be performed according to the patient clinical profile. Neuroimaging should be done in all cases. Non-contrasted computed tomography must be performed first. Magnetic resonance imaging is most useful for searching for more subtle structure abnormalities. Electroencephalogram, positron emission tomography and single photon emission computed tomography are not recommended as routine studies. Brain biopsy is indicated in few cases. Conclusion. Most common causes of reversible and treatable dementias include: medications, obstructive hydrocephalus, infectious, vascular, immunological, psychiatric, toxic and metabolic disorders, among others. © 2006, Revista de Neurologia.",Cognitive impairment;Computed axial tomography;Dementia;Neuroimaging;acquired immune deficiency syndrome/dt [Drug Therapy];acquired immune deficiency syndrome/pc [Prevention];alcoholism;autoimmune disease;blood cell count;brain biopsy;brain ischemia;brain vasculitis;cerebrospinal fluid analysis;cyanocobalamin deficiency/dt [Drug Therapy];delirium;depression/dt [Drug Therapy];electrocardiography;electroencephalogram;epidural hematoma;erythrocyte sedimentation rate;folic acid blood level;folic acid deficiency/dt [Drug Therapy];folic acid deficiency/th [Therapy];glioma/su [Surgery];human;Human immunodeficiency virus;hydrocephalus;hypercalcemia/dt [Drug Therapy];hyperthyroidism/dt [Drug Therapy];hyponatremia/dt [Drug Therapy];hypothyroidism/dt [Drug Therapy];intestine lipodystrophy/dt [Drug Therapy];kidney failure;liver function test;lung disease;Lyme disease/dt [Drug Therapy];meningioma/su [Surgery];meningitis;multiinfarct dementia;neurosyphilis;paraneoplastic neuropathy;pellagra/dt [Drug Therapy];positron emission tomography;protein electrophoresis;review;single photon emission computer tomography;subdural hematoma;syphilis serology;thiamine deficiency;thorax radiography;thyroid function test;urinalysis;vitamin blood level;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];cephalosporin/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];cotrimoxazole/dt [Drug Therapy];cyanocobalamin/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];folic acid/dt [Drug Therapy];folic acid/po [Oral Drug Administration];mineralocorticoid/dt [Drug Therapy];monoamine oxidase inhibitor/dt [Drug Therapy];nicotinamide/dt [Drug Therapy];nicotinamide/po [Oral Drug Administration];penicillamine/dt [Drug Therapy];tetracycline/dt [Drug Therapy];thyroid hormone/dt [Drug Therapy];tricyclic antidepressant agent/dt [Drug Therapy];trientine/dt [Drug Therapy];zidovudine/dt [Drug Therapy],"Senties-Madrid, H.;Estanol-Vidal, B.",2006,July,,0,0,
2073,A patient with Sanfilippo syndrome type B and Wilson disease born to unrelated parents. [Japanese],"A 5- year -old boy visited a hospital because of macrocephalus, mental retardation and hepatic dysfunction, and was suspected to have Wilson's disease since his father had this disease. The serum level of ceruloplasmin was low, but urinary copper excretion was not increased markedly. He was treated with D-penicillamine. He was then reffered to our hospital because of his facial features suggesting mucopolysaccharidosis. Based on mucopolysacchariduria and the deficiency of N-acetylglucosaminidase, the diagnosis of Sanfilippo syndrome type B was made. Molecular analyses identified him as a compound heterozygote for both the ATP7B (A844V/2659delG) and alpha -N-acetylglucosaminidase (V241M/R482W) genes, responsible for Wilson's disease and Sanfilippo syndrome type B, respectively. Although born to non-consanguineous parents, he had two rare autosomal recessive diseases. In this case, liver dysfunction was attributed to Wilson's disease, and mental retardation to Sanfilippo syndrome.",article;autosomal recessive disorder/cn [Congenital Disorder];autosomal recessive disorder/di [Diagnosis];brain malformation/cn [Congenital Disorder];brain malformation/di [Diagnosis];case report;consanguinity;copper metabolism;face malformation/cn [Congenital Disorder];face malformation/di [Diagnosis];genotype;heterozygosity;human;liver dysfunction/cn [Congenital Disorder];liver dysfunction/di [Diagnosis];macrocephaly/cn [Congenital Disorder];macrocephaly/di [Diagnosis];male;mental retardation malformation syndrome/cn [Congenital Disorder];mental retardation malformation syndrome/di [Diagnosis];molecular genetics;mucopolysaccharidosis/cn [Congenital Disorder];mucopolysaccharidosis/di [Diagnosis];phenotype;preschool child;Sanfilippo syndrome/cn [Congenital Disorder];Sanfilippo syndrome/di [Diagnosis];Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];acetylglucosaminidase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy],"Takaura, N.;Tanaka, A.;Yoshida, T.;Takeshita, Y.;Shimizu, N.;Aoki, T.;Tamai, H.;Yamano, T.",2006,,,0,0,
2074,Amyotrophic lateral sclerosis in younger age associated with abnormality of copper level. [Bosnian],"Amyotrophic lateral sclerosis is a progressive degenerative neuromuscular disease in adults that occurs in familial and sporadic forms. The mean age of onset of symptoms is 56 years and the mean duration of disease is 3 years. One of the theories on the pathogenesis suggests on mutation in gene that encodes superoxide dismutase, which is involved in metabolism of free radicals (copper, zinc). In this article we showed patient with early onset of disease associated with abnormality of copper level. Co morbidity with Wilson disease has not been proved. According to this case it is possible to think about changes in cuprum level at ALS patients.",adult;amyotrophic lateral sclerosis;article;blood;case report;human;male;onset age;copper,"Ibrahimagic, O. C.;Sinanovic, O.;Zonic, L.;Hudic, J.",2006,,,0,0,
2075,The neurology of enteric disease,"The role of liver failure in the development of various neuropathologies is well established. With regard to gluten-sensitive enteropathy, inflammatory bowel and pancreatic disease, most published evidence suggesting that these conditions are associated with neurological complications is at the level of case reportage rather than well-conducted epidemiological surveys. Coeliac disease seems to be associated with a unique syndrome in Italian populations and is characterised by occipital calcification and seizures. The role of gluten as a potential neurotoxin is disputed. Whipple's disease and Wilson's disease, although exceedingly rare, are both potentially treatable but still far more likely to be discussed in grand rounds than seen in real life!",abscess/co [Complication];alpha tocopherol deficiency/co [Complication];alpha tocopherol deficiency/dt [Drug Therapy];anorexia nervosa;ataxia/co [Complication];ataxia/si [Side Effect];beriberi/co [Complication];blood clotting disorder/si [Side Effect];brain disease/co [Complication];brain metastasis/co [Complication];carcinomatous meningitis/co [Complication];celiac disease/di [Diagnosis];central pontine myelinolysis/co [Complication];chorea/co [Complication];clinical feature;cognitive defect/dt [Drug Therapy];coma/co [Complication];constipation/si [Side Effect];Crohn disease;cyanocobalamin deficiency/co [Complication];degenerative disease/co [Complication];dementia/co [Complication];diarrhea/si [Side Effect];diet supplementation;diplopia/co [Complication];dyspepsia/si [Side Effect];eating disorder;epilepsy/co [Complication];eye malformation/co [Complication];flatulence/si [Side Effect];folic acid deficiency;gastrointestinal disease;gastrointestinal hemorrhage/si [Side Effect];gastrointestinal tract;Guillain Barre syndrome/co [Complication];headache/co [Complication];hepatic encephalopathy/co [Complication];hepatic encephalopathy/dt [Drug Therapy];human;Hypericum perforatum;hypothalamus disease/co [Complication];intestine lipodystrophy/dt [Drug Therapy];intestine lipodystrophy/et [Etiology];intracranial hypertension/co [Complication];kidney failure/co [Complication];liver disease;malabsorption/co [Complication];meningitis/co [Complication];Menkes syndrome/co [Complication];motor dysfunction/co [Complication];multiple sclerosis/co [Complication];muscle weakness/co [Complication];myoclonus/co [Complication];nausea and vomiting/si [Side Effect];nervous system;neurological complication/co [Complication];neurology;neuropathy/co [Complication];neuropathy/si [Side Effect];neuropathy/th [Therapy];nicotinic acid deficiency;nonhuman;obesity/dt [Drug Therapy];obesity/su [Surgery];optic nerve disease/co [Complication];optic neuritis/co [Complication];pancreas disease/dt [Drug Therapy];pancreatitis/si [Side Effect];parkinsonism/dt [Drug Therapy];pellagra/co [Complication];peripheral neuropathy/co [Complication];pica;plasmapheresis;priority journal;psychosis/co [Complication];retroperitoneal fibrosis/si [Side Effect];review;seizure/co [Complication];sensory neuropathy/co [Complication];side effect/si [Side Effect];spinal cord disease/co [Complication];spinal cord metastasis/co [Complication];stroke/si [Side Effect];sudden death;Syncope/co [Complication];thiamine deficiency;thrombotic thrombocytopenic purpura/co [Complication];ulcerative colitis;vein thrombosis/co [Complication];vitamin supplementation;weight gain;weight reduction;Wernicke encephalopathy/co [Complication];Wernicke Korsakoff syndrome/co [Complication];Wilson disease/dt [Drug Therapy];alpha tocopherol/ae [Adverse Drug Reaction];alpha tocopherol/dt [Drug Therapy];antibiotic agent/dt [Drug Therapy];carbamazepine/ae [Adverse Drug Reaction];catechol methyltransferase inhibitor/ae [Adverse Drug Reaction];cotrimoxazole/dt [Drug Therapy];cotrimoxazole/po [Oral Drug Administration];Ephedra extract/ae [Adverse Drug Reaction];ethosuximide/ae [Adverse Drug Reaction];etiracetam/ae [Adverse Drug Reaction];gabapentin/ae [Adverse Drug Reaction];Ginkgo biloba extract/ae [Adverse Drug Reaction];lamotrigine/ae [Adverse Drug Reaction];levodopa/ae [Adverse Drug Reaction];methysergide/ae [Adverse Drug Reaction];metronidazole/dt [Drug Therapy];neomycin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];piracetam/ae [Adverse Drug Reaction];pregabalin/ae [Adverse Drug Reaction];retinol/to [Drug Toxicity];sibutramine/dt [Drug Therapy];sibutramine/to [Drug Toxicity];tetrabenazine/ae [Adverse Drug Reaction];tetrahydrolipstatin/dt [Drug Therapy];tiagabine/ae [Adverse Drug Reaction];topiramate/to [Drug Toxicity];trientine/dt [Drug Therapy];triptan derivative/ae [Adverse Drug Reaction];unindexed drug;valproic acid/ae [Adverse Drug Reaction];vigabatrin/ae [Adverse Drug Reaction];vitamin D/to [Drug Toxicity],"Wills, A. J.;Pengiran Tengah, D. S. N. A.;Holmes, G. K. T.",2006,July,http://dx.doi.org/10.1136/jnnp.2005.085365,0,0,
2076,B<inf>6</inf>-responsive disorders: A model of vitamin dependency,"Pyridoxal phosphate is the cofactor for over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction, particularly epilepsy. There are several different mechanisms that lead to an increased requirement for pyridoxine and/or pyridoxal phosphate. These include: (i) inborn errors affecting the pathways of B<inf>6</inf> vitamer metabolism; (ii) inborn errors that lead to accumulation of small molecules that react with pyridoxal phosphate and inactivate it; (iii) drugs that react with pyridoxal phosphate; (iv) coeliac disease, which is thought to lead to malabsorption of B<inf>6</inf> vitamers; (v) renal dialysis, which leads to increased losses of B<inf>6</inf> vitamers from the circulation; (vi) drugs that affect the metabolism of B<inf>6</inf> vitamers; and (vii) inborn errors affecting specific pyridoxal phosphate-dependent enzymes. The last show a very variable degree of pyridoxine responsiveness, from 90% in X-linked sideroblastic anaemia (delta-aminolevulinate synthase deficiency) through 50% in homocystinuria (cystathionine beta-synthase deficiency) to 5% in ornithinaemia with gyrate atrophy (ornithine delta-aminotransferase deficiency). The possible role of pyridoxal phosphate as a chaperone during folding of nascent enzymes is discussed. High-dose pyridoxine or pyridoxal phosphate may have deleterious side-effects (particularly peripheral neuropathy with pyridoxine) and this must be considered in treatment regimes. None the less, in some patients, particularly infants with intractable epilepsy, treatment with pyridoxine or pyridoxal phosphate can be life-saving, and in other infants with inborn errors of metabolism B<inf>6</inf> treatment can be extremely beneficial. © SSIEM and Springer 2006.",article;dietary intake;drug absorption;drug activity;drug efficacy;drug megadose;drug potency;drug structure;epilepsy/dt [Drug Therapy];homocystinuria/dt [Drug Therapy];homocystinuria/et [Etiology];human;hyperprolinemia/et [Etiology];hypervitaminosis/et [Etiology];hypophosphatasia/et [Etiology];inborn error of metabolism/dt [Drug Therapy];liver toxicity/si [Side Effect];neurologic disease/si [Side Effect];neurotoxicity/si [Side Effect];nonhuman;peripheral neuropathy/si [Side Effect];pyridoxine deficiency/di [Diagnosis];pyridoxine deficiency/dt [Drug Therapy];pyridoxine deficiency/et [Etiology];seizure/si [Side Effect];structure analysis;tuberculosis/dt [Drug Therapy];vitamin metabolism;vitamin supplementation;Wilson disease/dt [Drug Therapy];X linked sideroblastic anemia/dt [Drug Therapy];X linked sideroblastic anemia/et [Etiology];5 aminolevulinate synthase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];carbidopa/it [Drug Interaction];chaperone;cycloserine/it [Drug Interaction];cystathionine beta synthase/ec [Endogenous Compound];hydralazine/it [Drug Interaction];isoniazid/it [Drug Interaction];isoniazid/dt [Drug Therapy];ornithine oxoacid aminotransferase/ec [Endogenous Compound];penicillamine/it [Drug Interaction];penicillamine/dt [Drug Therapy];pyridoxal/dt [Drug Therapy];pyridoxal 5 phosphate/ae [Adverse Drug Reaction];pyridoxal 5 phosphate/an [Drug Analysis];pyridoxal 5 phosphate/do [Drug Dose];pyridoxal 5 phosphate/it [Drug Interaction];pyridoxal 5 phosphate/dt [Drug Therapy];pyridoxal 5 phosphate/po [Oral Drug Administration];pyridoxal 5 phosphate/pk [Pharmacokinetics];pyridoxine/ae [Adverse Drug Reaction];pyridoxine/an [Drug Analysis];pyridoxine/do [Drug Dose];pyridoxine/it [Drug Interaction];pyridoxine/dt [Drug Therapy];pyridoxine/ip [Intraperitoneal Drug Administration];pyridoxine/iv [Intravenous Drug Administration];pyridoxine/pk [Pharmacokinetics];pyrroline 5 carboxylate reductase/ec [Endogenous Compound],"Clayton, P. T.",2006,April,http://dx.doi.org/10.1007/s10545-005-0243-2,0,0,
2077,Zinc requirements and the risks and benefits of zinc supplementation,"The adult human contains 2-3 g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that {greater than or slanted equal to}25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research. © 2006 Elsevier GmbH. All rights reserved.",Requirements;Supplementation;Zinc;abdominal cramp;absorption;acanthosis/co [Complication];acrodermatitis enteropathica/dt [Drug Therapy];article;bioavailability;bleeding;blood pressure regulation;cancer susceptibility;cell hyperplasia/co [Complication];chronic toxicity;clinical feature;copper deficiency;data analysis;diabetes mellitus;diarrhea;erythrocyte;evaluation;food handling;food preference;food preservation;food processing;gene control;genome imprinting;health hazard;hematologic disease/co [Complication];human;leukocyte;measurement;nausea;nonhuman;nutritional requirement;parakeratosis/co [Complication];population;precancer/co [Complication];priority journal;reference value;risk assessment;risk benefit analysis;safety;sensitivity and specificity;socioeconomics;stomach cancer/co [Complication];tenesmus;tongue cancer/co [Complication];treatment duration;vomiting;Wilson disease/dt [Drug Therapy];zinc blood level;zinc deficiency/dt [Drug Therapy];zinc deficiency/et [Etiology];zinc metabolism;biological marker/ec [Endogenous Compound];copper;zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity];zinc/po [Oral Drug Administration];zinc/pd [Pharmacology];zinc acetate/dt [Drug Therapy],"Maret, W.;Sandstead, H. H.",2006,10 May,http://dx.doi.org/10.1016/j.jtemb.2006.01.006,0,0,
2078,"Two novel mutations (2976INSA, 4311INSA) of ATP7B in a patient with Wilson's disease coexisting with glucose-6-phosphate dehydrogenase deficiency [3]",,autosomal recessive disorder/di [Diagnosis];case report;chromosome 13q;clinical feature;exon;gene;gene mutation;glucose 6 phosphate dehydrogenase deficiency/et [Etiology];human;INSA gene;letter;lung tuberculosis/dt [Drug Therapy];male;onset age;preschool child;priority journal;sepsis/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];ciprofloxacin/dt [Drug Therapy];ethambutol/dt [Drug Therapy];glucose 6 phosphate dehydrogenase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];rifampicin/dt [Drug Therapy];streptomycin/dt [Drug Therapy];tuberculostatic agent/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Prasad, R.;Kaur, G.;Kumar, S.;Thapa, B. R.",2005,April,http://dx.doi.org/10.1111/j.1440-1746.2005.03781.x,0,0,
2079,Non-surgical potentially reversible dementias. [Spanish],"Aims. In this study, we review dementias that are potentially reversible. The paper summarises the causes that essentially require management by medical means, while causes of a surgical nature will be dealt with in a second article. These papers attempt to avoid mistaken diagnoses and labels in patients with a high potential to improve their cognitive disorder and to guide us towards a more suitable management. Development. Dementia is a public health problem, mainly in countries with long life expectancy. It has an incidence of 3-11% in patients over the age of 65, and 20-50% in those over 85 years old. Most of them (50-70%) have Alzheimer-type dementia, followed by the vascular type (20%); there is a smaller percentage of cases of the so-called subcortical dementias and also those secondary to medical and/or surgical conditions that suggest potential reversibility. These latter cases are not easy to recognise and their incidence, depending on the series, ranges from 0 to 37%. Once they have been diagnosed, it is still difficult to state whether they will in fact turn out to be reversible. Their most common causes, such as deficiencies, metabolic disorders, chronic diseases, toxins, and so on, must be detected as early as possible, which can be done by means of clinical observation and use of the laboratory. Conclusions. Although the potential to improve in patients with a diagnosis of reversible dementia is still subject to discussion, this brief review guides us in the search for their causes and their management, since late detection and management are very likely to be the cause of a poor progression. © 2005, Revista de NeurologiA.",Reversible dementias;Symptomatic dementias;age;aged;Alzheimer disease;chronic disease;chronic hepatitis;chronic lung disease;cognitive defect;computer assisted tomography;congestive heart failure;cryptococcosis/dt [Drug Therapy];cyanocobalamin deficiency;dementia/di [Diagnosis];dementia/dt [Drug Therapy];dementia/et [Etiology];dementia/si [Side Effect];diabetes mellitus/dt [Drug Therapy];diagnostic imaging;early diagnosis;electroencephalography;enzyme linked immunosorbent assay;epilepsy/dt [Drug Therapy];general condition improvement;human;hypocalcemia;hypoglycemia;hypokalemia;hyponatremia;incidence;kidney failure;laboratory test;life expectancy;liver cirrhosis;lumbar puncture;metabolic disorder;multiinfarct dementia;neurosyphilis/dt [Drug Therapy];nutritional deficiency;observation;parathyroid disease;positron emission tomography;pseudodementia;review;risk factor;single photon emission computer tomography;symptom;thiamine deficiency;thyroid disease/dt [Drug Therapy];tuberculosis/dt [Drug Therapy];urinary tract infection;Western blotting;Wilson disease/dt [Drug Therapy];alcohol/to [Drug Toxicity];amphotericin B/do [Drug Dose];amphotericin B/dt [Drug Therapy];anticonvulsive agent/ae [Adverse Drug Reaction];anticonvulsive agent/dt [Drug Therapy];antidepressant agent/ae [Adverse Drug Reaction];antihypertensive agent/ae [Adverse Drug Reaction];anxiolytic agent/ae [Adverse Drug Reaction];bethanechol/ae [Adverse Drug Reaction];calcium/dt [Drug Therapy];calcium/ec [Endogenous Compound];cholinergic receptor blocking agent/ae [Adverse Drug Reaction];cyanocobalamin/dt [Drug Therapy];cyanocobalamin/ec [Endogenous Compound];flucytosine/do [Drug Dose];flucytosine/dt [Drug Therapy];glucose/ec [Endogenous Compound];hypnotic agent/ae [Adverse Drug Reaction];insulin/dt [Drug Therapy];isoniazid/cb [Drug Combination];isoniazid/dt [Drug Therapy];levothyroxine/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];nicotinic acid/dt [Drug Therapy];nicotinic acid/ec [Endogenous Compound];oral antidiabetic agent/dt [Drug Therapy];oral antidiabetic agent/po [Oral Drug Administration];oxybutynin/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillin G/dt [Drug Therapy];prednisone/do [Drug Dose];prednisone/dt [Drug Therapy];propranolol/dt [Drug Therapy];pyrazinamide/cb [Drug Combination];pyrazinamide/dt [Drug Therapy];pyridoxine derivative/cb [Drug Combination];pyridoxine derivative/do [Drug Dose];pyridoxine derivative/dt [Drug Therapy];rifampicin/cb [Drug Combination];rifampicin/dt [Drug Therapy];sodium/dt [Drug Therapy];sodium/ec [Endogenous Compound];thiamine/dt [Drug Therapy];thiamine/ec [Endogenous Compound];unindexed drug,"Barquet-Platon, E. I.;Mercado-Pimentel, R.;Ortiz-Velazquez, R. I.;Cardona-Cabrera, S.;Otero-Siliceo, E.;Santos Franco, J. A.",2005,01 Jan,,0,0,
2080,History of Wilson's disease: 1912 to 2000,,autosomal recessive inheritance;chromosome 13q;clinical feature;copper metabolism;disease association;genotype phenotype correlation;hemolysis/co [Complication];human;liver cirrhosis;liver failure/co [Complication];liver failure/su [Surgery];liver injury;liver transplantation;long term care;mortality;neurologic disease;nonhuman;pathogenesis;priority journal;prognosis;review;tissue level;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper exporting adenosine triphosphatase/ec [Endogenous Compound];copper protein/ec [Endogenous Compound];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Walshe, J. M.",2006,February,http://dx.doi.org/10.1002/mds.20694,0,0,
2081,"Chronological changes in tissue copper, zinc and iron in the toxic milk mouse and effects of copper loading","The toxic milk (tx) mouse is a rodent model for Wilson disease, an inherited disorder of copper overload. Here we assessed the effect of copper accumulation in the tx mouse on zinc and iron metabolism. Copper, zinc and iron concentrations were determined in the liver, kidney, spleen and brain of control and copper-loaded animals by atomic absorption spectroscopy. Copper concentration increased dramatically in the liver, and was also significantly higher in the spleen, kidney and brain of control tx mice in the first few months of life compared with normal DL mice. Hepatic zinc was increased with age in the tx mouse, but zinc concentrations in the other organs were normal. Liver and kidney iron concentrations were significantly lower at birth in tx mice, but increased quickly to be comparable with control mice by 2 months of age. Iron concentration in the spleen was significantly higher in tx mice, but was lower in 5 day old tx pups. Copper-loading studies showed that normal DL mice ingesting 300 mg/l copper in their diet for 3 months maintained normal liver, kidney and brain copper, zinc and iron levels. Copper-loading of tx mice did not increase the already high liver copper concentrations, but spleen and brain copper concentrations were increased. Despite a significant elevation of copper in the brain of the copper-loaded tx mice no behavioural changes were observed. The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants. © Springer 2006.",Copper;Iron;Toxic milk mouse;Wilson disease;Zinc;age;animal experiment;animal tissue;article;atomic absorption spectrometry;behavior change;birth;brain;chronology;controlled study;diet;female;hemolysis;iron metabolism;kidney;liver;male;mouse;mutant;nonhuman;organ;spleen;zinc metabolism,"Allen, K. J.;Buck, N. E.;Cheah, D. M. Y.;Gazeas, S.;Bhathal, P.;Mercer, J. F. B.",2006,October,http://dx.doi.org/10.1007/s10534-005-5918-5,0,0,
2082,Orphan drug development is progressing too slowly,"Aims: To assess the methodological quality of OMP dossiers and to discuss possible reasons for the small number of products licensed. Methods: Information about orphan drug designation and approval was obtained from the website of the European Commission-Enterprise and Industry DG and from the European Public Assessment Reports. Results: Out of 255 OMP designations, only 18 were approved (7.1%). Their dossiers often showed methodological limitations such as inappropriate clinical design, lack of active comparator where available and use of surrogate end-points. Conclusions: The paucity of European incentives for manufacturers and the poor documentation underpinning the applications may have limited the number of new OMP. The over 5000 rare diseases awaiting therapy are an important public health issue. © 2006 Blackwell Publishing Ltd.",Development;Orphan drugs;Rare diseases;acromegaly/dt [Drug Therapy];adenomatous polyp/dt [Drug Therapy];adrenal cortex carcinoma/dt [Drug Therapy];article;carcinogenicity;chronic myeloid leukemia/dt [Drug Therapy];clinical trial;drug approval;drug design;drug industry;drug information;drug manufacture;drug use;dysplasia/dt [Drug Therapy];Fabry disease/dt [Drug Therapy];Gaucher disease/dt [Drug Therapy];genotoxicity;hairy cell leukemia/dt [Drug Therapy];hematopoietic stem cell transplantation;human;Internet;licensing;mucopolysaccharidosis/dt [Drug Therapy];nonhuman;priority journal;promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];thrombocythemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/ct [Clinical Trial];agalsidase alfa/dv [Drug Development];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/to [Drug Toxicity];agalsidase beta/ct [Clinical Trial];agalsidase beta/dv [Drug Development];agalsidase beta/dt [Drug Therapy];agalsidase beta/to [Drug Toxicity];alemtuzumab;alitretinoin;anagrelide/ct [Clinical Trial];anagrelide/dv [Drug Development];anagrelide/dt [Drug Therapy];anagrelide/to [Drug Toxicity];arsenic trioxide/ct [Clinical Trial];arsenic trioxide/dv [Drug Development];arsenic trioxide/dt [Drug Therapy];arsenic trioxide/to [Drug Toxicity];arylbutyric acid derivative;blood clotting factor 7a;blood clotting factor 9;bosentan/ct [Clinical Trial];bosentan/dv [Drug Development];bosentan/dt [Drug Therapy];bosentan/to [Drug Toxicity];busilvex;busulfan/ct [Clinical Trial];busulfan/dv [Drug Development];busulfan/dt [Drug Therapy];busulfan/to [Drug Toxicity];carglumic acid/ct [Clinical Trial];carglumic acid/dv [Drug Development];carglumic acid/dt [Drug Therapy];carglumic acid/to [Drug Toxicity];celecoxib/ct [Clinical Trial];celecoxib/dv [Drug Development];celecoxib/dt [Drug Therapy];celecoxib/to [Drug Toxicity];cladribine/ct [Clinical Trial];cladribine/dv [Drug Development];cladribine/dt [Drug Therapy];cladribine/to [Drug Toxicity];deferiprone;ibuprofen/ct [Clinical Trial];ibuprofen/dv [Drug Development];ibuprofen/dt [Drug Therapy];ibuprofen/to [Drug Toxicity];iloprost/ct [Clinical Trial];iloprost/dv [Drug Development];iloprost/dt [Drug Therapy];iloprost/to [Drug Toxicity];imatinib/ct [Clinical Trial];imatinib/dv [Drug Development];imatinib/dt [Drug Therapy];imatinib/to [Drug Toxicity];imiglucerase;laronidase/ct [Clinical Trial];laronidase/dv [Drug Development];laronidase/dt [Drug Therapy];laronidase/to [Drug Toxicity];litak;mercaptamine;miglustat/ct [Clinical Trial];miglustat/dv [Drug Development];miglustat/dt [Drug Therapy];miglustat/to [Drug Toxicity];mitotane/ct [Clinical Trial];mitotane/dv [Drug Development];mitotane/dt [Drug Therapy];mitotane/to [Drug Toxicity];orphan drug/ct [Clinical Trial];orphan drug/dv [Drug Development];orphan drug/dt [Drug Therapy];orphan drug/to [Drug Toxicity];pegvisomant/ct [Clinical Trial];pegvisomant/dv [Drug Development];pegvisomant/dt [Drug Therapy];pegvisomant/to [Drug Toxicity];photofrin/ct [Clinical Trial];photofrin/dv [Drug Development];photofrin/dt [Drug Therapy];photofrin/to [Drug Toxicity];protein C;riluzole;unindexed drug;wilzin;zinc acetate/ct [Clinical Trial];zinc acetate/dv [Drug Development];zinc acetate/dt [Drug Therapy];zinc acetate/to [Drug Toxicity],"Joppi, R.;Bertele, V.;Garattini, S.",2006,March,http://dx.doi.org/10.1111/j.1365-2125.2006.02579.x,0,0,
2083,Copper: Role of the 'endogenous' and 'exogenous' metal on the development and control of inflammatory processes,,Anti-inflammatory agents;Copper anti-inflammatory activity;Copper/acute experimental inflammation;Copper/chronic experimental inflammation;Copper/deficiency;Copper/metabolism;Copper/rheumatoid arthritis;Copper/therapeutic use;Non-steroidal;acute disease;adjuvant arthritis;antiinflammatory activity;arthritis/dt [Drug Therapy];cardiotoxicity/si [Side Effect];chronic inflammation;clinical trial;connective tissue;controlled clinical trial;copper blood level;copper deficiency;copper metabolism;disease control;disease severity;drug absorption;drug bioavailability;drug efficacy;drug safety;electrolyte blood level;environmental exposure;enzyme activity;exudate;gastrointestinal symptom/si [Side Effect];glucose blood level;histamine release;homeostasis;human;immune response;immune system;immunoreactivity;inflammation/et [Etiology];inflammation/pc [Prevention];ischemia/si [Side Effect];leukocyte activation;leukocyte migration;liver;liver toxicity/si [Side Effect];lung toxicity/si [Side Effect];multiple cycle treatment;nausea/si [Side Effect];nephrotoxicity/si [Side Effect];neurotoxicity/si [Side Effect];neutrophil chemotaxis;nonhuman;pathogenesis;paw edema;prostaglandin synthesis;review;rheumatoid arthritis/et [Etiology];side effect/si [Side Effect];tinnitus/si [Side Effect];typhoid fever/dt [Drug Therapy];typhoid fever/pc [Prevention];urinalysis;Wilson disease/dt [Drug Therapy];acetylsalicylate copper/cm [Drug Comparison];acetylsalicylate copper/po [Oral Drug Administration];acetylsalicylate copper/pa [Parenteral Drug Administration];acetylsalicylate copper/pd [Pharmacology];acetylsalicylate copper/sc [Subcutaneous Drug Administration];acetylsalicylic acid/cm [Drug Comparison];acetylsalicylic acid/dt [Drug Therapy];alcusal;antimalarial agent/cm [Drug Comparison];basic copper carbonate/pd [Pharmacology];basic copper carbonate/sc [Subcutaneous Drug Administration];copper/ad [Drug Administration];copper/cm [Drug Comparison];copper/cr [Drug Concentration];copper/dt [Drug Therapy];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper/iv [Intravenous Drug Administration];copper/pk [Pharmacokinetics];copper/pd [Pharmacology];copper/sc [Subcutaneous Drug Administration];copper acetate/cr [Drug Concentration];copper acetate/dt [Drug Therapy];copper acetate/po [Oral Drug Administration];copper acetate/pd [Pharmacology];copper acetate/sc [Subcutaneous Drug Administration];copper alanine/po [Oral Drug Administration];copper alanine/pd [Pharmacology];copper anthranilate/pd [Pharmacology];copper anthranilate/sc [Subcutaneous Drug Administration];copper chloride/pd [Pharmacology];copper chloride/sc [Subcutaneous Drug Administration];copper complex/ad [Drug Administration];copper complex/cb [Drug Combination];copper complex/cr [Drug Concentration];copper complex/dt [Drug Therapy];copper complex/ip [Intraperitoneal Drug Administration];copper complex/iv [Intravenous Drug Administration];copper complex/po [Oral Drug Administration];copper complex/pk [Pharmacokinetics];copper complex/pd [Pharmacology];copper complex/sc [Subcutaneous Drug Administration];copper metallothionein/ip [Intraperitoneal Drug Administration];copper metallothionein/pd [Pharmacology];copper oxide/po [Oral Drug Administration];copper oxide/pd [Pharmacology];copper oxide/sc [Subcutaneous Drug Administration];copper piroxicam/ip [Intraperitoneal Drug Administration];copper piroxicam/pd [Pharmacology];copper salicylate/ae [Adverse Drug Reaction];copper salicylate/cm [Drug Comparison];copper salicylate/dt [Drug Therapy];copper salicylate/iv [Intravenous Drug Administration];copper thiomalate/pd [Pharmacology];copper thiomalate/sc [Subcutaneous Drug Administration];copper tryptophan/ip [Intraperitoneal Drug Administration];copper tryptophan/pd [Pharmacology];copper zinc superoxide dismutase/pd [Pharmacology];copper zinc superoxide dismutase/sc [Subcutaneous Drug Administration];cortisone/cm [Drug Comparison];cysteine copper/ip [Intraperitoneal Drug Administration];cysteine copper/pd [Pharmacology];dermuscal;fenamole copper acetate/pd [Pharmacology];fenamole copper acetate/sc [Subcutaneous Drug Administration];gold derivative/cm [Drug Comparison];gold salt/cm [Drug Comparison];histidine copper/ip [Intraperitoneal Drug Administration];histidine copper/pd [Pharmacology];nonsteroid antiinflammatory agent/cm [Drug Comparison];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];salicylate sodium/ct [Clinical Trial];salicylic acid/cb [Drug Combination];salicylic acid/dt [Drug Therapy];salicylic acid derivative/dt [Drug Therapy];salicylic acid derivative/iv [Intravenous Drug Administration];typhoid vaccine/ad [Drug Administration];typhoid vaccine/dt [Drug Therapy];unclassified drug;unindexed drug,"Milanino, R.;Buchner, V.",2006,July/September,,0,0,
2084,The treatment of hepatic fibrosis: Reversal of the underlying disease process,"Cirrhosis is considered an irreversible end stage of all liver diseases. Current knowledge indicates that fibrosis is part of the liver repair process, which is dynamic. Understanding this repair process will provide better approaches to halt, ameliorate, or reverse fibrosis. The diagnosis of cirrhosis is currently established by liver biopsy and in most advanced cases can be confirmed by imaging. Liver biopsy remains the gold standard but has several limitations: sampling error, size of the biopsy, and both inter- and intra-observer inconsistencies. Hence, many patients can be inaccurately staged for the degree of fibrosis on their initial biopsy, as well as on subsequent re-examination. Although a decrease of 1 stage between consecutive biopsies may be a result of sampling error, the reduction from cirrhosis by at least 2 stages more likely represents a reversal of cirrhosis. There are several cases of reversal of cirrhosis reported in association with different liver diseases. The resolution of fibrosis in the majority of these diseases is related to successful treatment of the underlying etiology (eg, hepatitis B, hepatitis C, iron overload, Wilson disease, alcohol abstinence, metabolic syndrome in fatty liver disease, and decompression of biliary obstruction). The other important feature of reversal of cirrhosis is the successful control of inflammation (eg, autoimmune hepatitis, primary biliary cirrhosis, hepatitis B, C, and D).",Biliary obstruction;Cirrhosis reversal;Fibrosis regression;Hepatitis;Nonalcoholic steatohepatitis;alcohol abstinence;alcohol liver cirrhosis/dt [Drug Therapy];article;autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];bile duct obstruction;bone marrow transplantation;ceruloplasmin blood level;clinical feature;clinical trial;delta agent hepatitis/dt [Drug Therapy];diagnostic accuracy;diagnostic imaging;disease association;disease control;disease course;drug megadose;drug withdrawal;extracellular matrix;gold standard;hemochromatosis;hemosiderosis;hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];hepatitis C/su [Surgery];hepatitis C/th [Therapy];human;immunosuppressive treatment;insulin resistance;iron balance;iron overload/di [Diagnosis];iron overload/dt [Drug Therapy];liver biopsy;liver cirrhosis/co [Complication];liver cirrhosis/di [Diagnosis];liver cirrhosis/et [Etiology];liver fibrosis/co [Complication];liver fibrosis/dt [Drug Therapy];liver regeneration;low drug dose;metabolic syndrome X;nonalcoholic fatty liver/di [Diagnosis];nonalcoholic fatty liver/su [Surgery];nonalcoholic fatty liver/th [Therapy];observer bias;phlebotomy;primary biliary cirrhosis/dt [Drug Therapy];remission;sampling error;sclerosing cholangitis;thalassemia/th [Therapy];urinalysis;weight reduction;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adefovir/dt [Drug Therapy];alpha2 interferon/do [Drug Dose];alpha2 interferon/dt [Drug Therapy];alpha2a interferon/dt [Drug Therapy];azathioprine/ct [Clinical Trial];azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];colchicine/dt [Drug Therapy];copper ion/ec [Endogenous Compound];corticosteroid/cb [Drug Combination];corticosteroid/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];interferon/dt [Drug Therapy];iron/ec [Endogenous Compound];lamivudine/ct [Clinical Trial];lamivudine/dt [Drug Therapy];mercaptopurine/ct [Clinical Trial];mercaptopurine/cb [Drug Combination];mercaptopurine/dt [Drug Therapy];methotrexate/ct [Clinical Trial];methotrexate/cb [Drug Combination];methotrexate/dt [Drug Therapy];peginterferon alpha2b/ct [Clinical Trial];peginterferon alpha2b/cb [Drug Combination];peginterferon alpha2b/dt [Drug Therapy];penicillamine/dt [Drug Therapy];placebo;prednisone/dt [Drug Therapy];ribavirin/ct [Clinical Trial];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];ursodeoxycholic acid/ct [Clinical Trial];ursodeoxycholic acid/cb [Drug Combination];ursodeoxycholic acid/dt [Drug Therapy],"Servin-Abad, L.;Schiff, E. R.",2006,November,,0,0,
2085,Wilson's disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes,"Cases with a clinical and electroencephalographic phenotype of benign epilepsy of childhood with centrotemporal spikes (BECTS) in association with a proven organic brain lesion have rarely been reported. To our knowledge, we herein describe for the first time a patient with Wilson's disease who subsequently manifested BECTS. Our case bolsters the argument that in at least some cases, BECTS is associated with organic brain disease. © 2005 Elsevier Inc. All rights reserved.",Clinical pattern;Electroencephalographic pattern;Rolandic epilepsy;Wilson's disease;article;benign childhood epilepsy/di [Diagnosis];benign childhood epilepsy/dt [Drug Therapy];benign childhood epilepsy/et [Etiology];brain damage/et [Etiology];case report;clinical feature;computer assisted tomography;diet restriction;disease course;drug dose regimen;electroencephalography;female;human;informed consent;laboratory test;neurologic examination;patient compliance;phenotype;rolandic epilepsy/di [Diagnosis];rolandic epilepsy/dt [Drug Therapy];rolandic epilepsy/et [Etiology];school child;spike;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];carbamazepine/do [Drug Dose];carbamazepine/dt [Drug Therapy];copper;zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy],"Polychronopoulos, P.;Argyriou, A. A.;Papapetropoulos, S.;Gourzis, P.;Rigas, G.;Chroni, E.",2006,March,http://dx.doi.org/10.1016/j.yebeh.2005.12.008,0,0,
2086,Wilson's disease. [Spanish],,article;clinical feature;cutis laxa/si [Side Effect];diet;Goodpasture syndrome/si [Side Effect];human;hypersensitivity reaction/si [Side Effect];liver toxicity;myasthenia gravis/si [Side Effect];nephrotic syndrome/si [Side Effect];optic neuritis/si [Side Effect];pyridoxine deficiency/si [Side Effect];systemic lupus erythematosus/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];cupripen;penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Bruguera, M.",2006,January,http://dx.doi.org/10.1157/13083259,0,0,
2087,Metabolic disease as a cause of chronic liver disease in children,"Metabolic disease is an important cause of chronic liver disease, and recognizing this association is important for guiding prognostication, genetic counselling and therapy. The most important part of the diagnostic process is often the act of considering metabolic liver disease as a possible cause of the symptoms. Chronic liver disease has a number of possible phenotypes, and a range of metabolic diseases can account for these. A logical approach is first to define the phenotype and then to consider pointers that might suggest metabolic disease. These could include family history, the relationship of symptoms to feeding or fasting and possible dietary precipitants. Specific diagnosis will usually depend on selecting laboratory tests in a logical manner, having defined the phenotype and considered the potential metabolic causes. It is important that algorithms for the investigation of common phenotypes are developed locally in collaboration between clinicians and laboratory scientists. © 2005 Elsevier Ltd. All rights reserved.",Chronic liver disease;Clinical phenotypes;Glycogen storage diseases;Metabolic liver disease;Neonatal liver disease;Organomegaly;abdominal discomfort/si [Side Effect];alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/su [Surgery];anemia/si [Side Effect];bile acid synthesis;bone marrow suppression/si [Side Effect];cholestasis;cholesterol ester storage disease/di [Diagnosis];cholesterol ester storage disease/dt [Drug Therapy];cholesterol ester storage disease/su [Surgery];chronic liver disease/et [Etiology];clinical trial;diarrhea/co [Complication];disease association;drug mechanism;family history;fever/si [Side Effect];Gaucher disease/di [Diagnosis];Gaucher disease/dt [Drug Therapy];genetic counseling;glycogen storage disease type 1/di [Diagnosis];glycogen storage disease type 3/di [Diagnosis];glycogen storage disease type 4/su [Surgery];glycogen storage disease type 6/di [Diagnosis];human;intrahepatic cholestasis/su [Surgery];laboratory test;liver transplantation;metabolic disorder;Niemann Pick disease/dt [Drug Therapy];phenotype;postoperative complication;prognosis;proteinuria/si [Side Effect];rash/si [Side Effect];review;skin disease/si [Side Effect];steatosis/co [Complication];systemic lupus erythematosus/si [Side Effect];tyrosinemia/di [Diagnosis];tyrosinemia/dt [Drug Therapy];tyrosinemia/su [Surgery];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];cholic acid/dt [Drug Therapy];glucosylceramidase/dt [Drug Therapy];glucosylceramidase/pa [Parenteral Drug Administration];hydroxymethylglutaryl coenzyme A reductase inhibitor/dt [Drug Therapy];miglustat/dt [Drug Therapy];nitisinone/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pyridoxine/ae [Adverse Drug Reaction];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"McKiernan, P. J.",2006,February,http://dx.doi.org/10.1016/j.cupe.2005.10.001,0,0,
2088,Vasogenic edema-like pattern in Wilson's disease: Diffusion-weighted imaging findings,"Magnetic resonance imaging (MRI) is an efficient method for documenting involvement of the central nervous system in Wilson's disease, thus allowing better anatomical and clinical correlation. The neurologic symptoms of Wilson's disease are usually caused by cerebral copper accumulation sufficient to destroy nerve cells. Cranial MRI findings in cases of Wilson's disease have previously been described. We herein report a case of 9-year-old female patient with Wilson's disease, proved by liver biopsy, who underwent cranial diffusion-weighted MRI. © 2006 IOS Press. All rights reserved.",Diffusion-weighted MRI;Wilson's disease;anamnesis;article;brain region;case report;central nervous system disease/di [Diagnosis];clinical feature;copper metabolism;diagnostic accuracy;diagnostic value;diffusion coefficient;diffusion weighted imaging;female;human;human tissue;image analysis;image quality;laboratory test;liver biopsy;neurologic examination;nuclear magnetic resonance imaging;pathological anatomy;school child;slit lamp;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Atalar, M. H.;Icagasioglu, D.",2006,,,0,0,
2089,Wilson's disease: Forms of presentation in childhood. [Spanish],"Wilson's disease can manifest with symptoms of liver disease or neuropsychiatric disorders in children and adults. This autosomal recessive disorder is caused by a copper metabolism disorder due to a mutation in the ATP7B transporter. Excessive amounts of copper accumulate in the body due to inhibition of the release of copper into bile. Because effective treatment is available, recognizing this disease in presymptomatic or early stages, when it can be reversed, is highly important Diagnosis is often easy but the available tests (measurement of ceruloplasmin, and blood, urinary and liver copper levels) can be misleading. There is no single test with 100% sensitivity in screening nor do any of the tests, when used alone, provide 100% specificity. Diagnosis is currently based on the combination of clinical findings and the results of laboratory tests. Genetic study, with a finding of mutations in the two alleles of the ATP7B gene, is still not a rapid and easily available alternative and the absence of these mutations does not rule out the possible presence of other mutations not yet described.",article;autosomal recessive disorder;clinical feature;copper blood level;diagnostic procedure;gene mutation;genetic analysis;human;sensitivity and specificity;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper ion;penicillamine/dt [Drug Therapy];trientine/do [Drug Dose];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Jara Vega, P.;Hierro Llanillo, L.",2006,November,http://dx.doi.org/10.1157/13094353,0,0,
2090,Arterioportal fistula requiring liver transplantation,,adult;anamnesis;article;artificial embolism;ascites;case report;clinical feature;computer assisted tomography;disease severity;Doppler echography;dyspnea;echography;hepatic artery;human;human tissue;liver angiography;liver arteriovenous fistula/co [Complication];liver arteriovenous fistula/di [Diagnosis];liver arteriovenous fistula/su [Surgery];liver arteriovenous fistula/th [Therapy];liver biopsy;liver disease/co [Complication];liver disease/di [Diagnosis];liver disease/su [Surgery];liver disease/th [Therapy];liver failure/co [Complication];liver failure/di [Diagnosis];liver failure/su [Surgery];liver parenchyma;liver transplantation;male;muscle weakness;patient referral;portal vein;priority journal;stomach hemorrhage/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Duman, J. D.;Johnson, S. P.;Trotter, J. F.",2006,December,http://dx.doi.org/10.1002/lt.20989,0,0,
2091,Wilson disease. [French],"Wilson disease is an autosomal recessive disorder of copper overload. A principal characteristic of this disease is its wide phenotypic and genotypic variability. Its results from mutations of the ATP 7B gene located on chromosome 13, that encodes a hepatic copper transport protein. More than 300 mutations of this gene have been identified. This protein ensures the transport of copper in the hepatocyte, its incorporation with the apoceruloplasmin and its biliary excretion. The clinical manifestations are heterogeneous as well in their presentation, dominated by the neuropsychiatric and hepatic symptoms, as in the age of the first symptoms. Early recognition and initiation of therapy with chelators or zinc are essential for prognosis. Liver transplantation is indicated in cases with fulminant hepatitis, end-stage liver cirrhosis and should be considered in the therapy resistant neurological forms. A regular follow-up with monitoring of adverse effects of treatment and compliance is essential. Any discontinuation of treatments will involve, within a very variable time, but in constant manner, a reappearance or a reaggravation of the signs. Such relapses are often brutal and can be extremely serious, especially since response to subsequent treatment is often poor. © Masson.",Copper metabolism;Diagnosis;Genetics;Treatment;Wilson disease;autosomal recessive disorder;chromosome 13;clinical feature;follow up;gene location;gene mutation;genetic variability;genotype;hepatitis/di [Diagnosis];hepatitis/su [Surgery];human;liver cell;liver cirrhosis/di [Diagnosis];liver cirrhosis/su [Surgery];liver graft;liver transplantation;membrane transport;phenotype;prognosis;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];chelating agent/dt [Drug Therapy];zinc/dt [Drug Therapy],"Woimant, F.;Chaine, P.;Favrole, P.;Mikol, J.;Chappuis, P.",2006,June,,0,0,
2092,Intensive management of hepatic failure,"A substantial number of patients with liver failure are admitted to the intensive care unit; thus a thorough understanding of the prevention and treatment of complications in such patients is imperative. The management of liver failure is demanding and often involves the combined efforts of many specialists. Critically ill patients with hepatic failure encompass a broad spectrum of disease, ranging from acute liver failure in a patient with no prior history of liver disease, to acute on chronic liver failure. The initial assessment and management of acute liver failure are reviewed with an emphasis on the prevention and treatment of brain edema in the pretransplant setting. The current treatment of complications resulting from decompensated chronic liver disease such as portal hypertensive bleeding; infection, renal failure, and hepatic encephalopathy are then discussed. Copyright © 2006 by Thieme Medical Publishers, Inc.",Cerebral edema;Liver failure;Management;Portal hypertension;adrenal cortex insufficiency/co [Complication];Amanita phalloides;artificial ventilation;ascites/co [Complication];ascites/dt [Drug Therapy];ascites/su [Surgery];autoimmune hepatitis/dt [Drug Therapy];bacterial infection/co [Complication];bacterial infection/dt [Drug Therapy];bacterial infection/et [Etiology];bacterial infection/pc [Prevention];bacterial peritonitis/co [Complication];bacterial peritonitis/dt [Drug Therapy];bacterial peritonitis/et [Etiology];bacterial peritonitis/pc [Prevention];bleeding/co [Complication];bleeding/dt [Drug Therapy];bleeding/pc [Prevention];bleeding/th [Therapy];brain edema/co [Complication];brain edema/pc [Prevention];Budd Chiari syndrome/dt [Drug Therapy];Budd Chiari syndrome/su [Surgery];critically ill patient;device;endoscopic sclerotherapy;esophagus varices bleeding/co [Complication];esophagus varices bleeding/dt [Drug Therapy];esophagus varices bleeding/su [Surgery];esophagus varices bleeding/th [Therapy];fatty liver;HELLP syndrome;hemostasis;hepatic encephalopathy/co [Complication];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/et [Etiology];hepatitis B/dt [Drug Therapy];hepatorenal syndrome/co [Complication];hepatorenal syndrome/dt [Drug Therapy];hepatorenal syndrome/et [Etiology];hepatorenal syndrome/su [Surgery];herpes simplex/dt [Drug Therapy];Herpes simplex virus;human;hyperventilation;induced hypothermia;intensive care unit;intracranial hypertension/co [Complication];intracranial hypertension/di [Diagnosis];intracranial hypertension/dt [Drug Therapy];intracranial hypertension/pc [Prevention];intracranial hypertension/th [Therapy];jaundice/co [Complication];kidney failure/co [Complication];kidney failure/dt [Drug Therapy];kidney failure/et [Etiology];ligation;liver assist device;liver failure/co [Complication];liver failure/di [Diagnosis];liver failure/dt [Drug Therapy];liver failure/ep [Epidemiology];liver failure/et [Etiology];liver failure/si [Side Effect];liver failure/su [Surgery];liver failure/th [Therapy];liver toxicity/dt [Drug Therapy];liver toxicity/si [Side Effect];liver transplantation;multiple organ failure/co [Complication];mushroom poisoning/dt [Drug Therapy];mushroom poisoning/et [Etiology];paracentesis;portal hypertension/co [Complication];portal hypertension/dt [Drug Therapy];portal hypertensive gastropathy/co [Complication];portal hypertensive gastropathy/di [Diagnosis];portal hypertensive gastropathy/dt [Drug Therapy];portosystemic anastomosis;priority journal;review;sepsis/co [Complication];stomach disease/co [Complication];stomach disease/di [Diagnosis];stomach disease/dt [Drug Therapy];stomach varices/co [Complication];stomach varices/su [Surgery];stomach varices/th [Therapy];systemic inflammatory response syndrome/co [Complication];tampon;Wilson disease;acetylcysteine/dt [Drug Therapy];aciclovir/dt [Drug Therapy];albumin;antibiotic agent/cb [Drug Combination];antibiotic agent/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];cefotaxime/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];desmopressin/dt [Drug Therapy];diuretic agent/dt [Drug Therapy];hetastarch;indometacin/dt [Drug Therapy];lactulose/cb [Drug Combination];lactulose/dt [Drug Therapy];mannitol/dt [Drug Therapy];neomycin/cb [Drug Combination];neomycin/dt [Drug Therapy];norfloxacin/dt [Drug Therapy];norfloxacin/po [Oral Drug Administration];octreotide/dt [Drug Therapy];paracetamol/ae [Adverse Drug Reaction];penicillin G/dt [Drug Therapy];rifaximin/cb [Drug Combination];rifaximin/dt [Drug Therapy];silibinin/dt [Drug Therapy];sodium chloride;somatostatin/dt [Drug Therapy];terlipressin/dt [Drug Therapy];thiopental/dt [Drug Therapy];vasopressin/dt [Drug Therapy];zinc sulfate,"Rinella, M. E.;Sanyal, A.",2006,June,http://dx.doi.org/10.1055/s-2006-945528,0,0,
2093,Molybdenum,,absorption;angiogenesis;breast cancer/dt [Drug Therapy];breast cancer/et [Etiology];breast cancer/pc [Prevention];cauliflower;clinical trial;diet supplementation;dietary intake;drug blood level;drug clearance;drug mechanism;enzyme deficiency/dt [Drug Therapy];enzyme deficiency/et [Etiology];esophagus cancer/ep [Epidemiology];esophagus cancer/et [Etiology];esophagus cancer/pc [Prevention];grain;human;kidney cancer/dt [Drug Therapy];kidney clearance;leafy vegetable;legume;molybdenum cofactor deficiency/dt [Drug Therapy];molybdenum cofactor deficiency/et [Etiology];molybdenum deficiency/pc [Prevention];molybdenum deficiency/th [Therapy];nonhuman;nut;nutritional deficiency/pc [Prevention];nutritional deficiency/th [Therapy];review;stomach cancer/ep [Epidemiology];stomach cancer/et [Etiology];stomach cancer/pc [Prevention];total parenteral nutrition;Wilson disease/dt [Drug Therapy];aldehyde oxidase/ec [Endogenous Compound];copper/to [Drug Toxicity];molybdenum/ct [Clinical Trial];molybdenum/dt [Drug Therapy];molybdenum/to [Drug Toxicity];molybdenum/iv [Intravenous Drug Administration];molybdenum/po [Oral Drug Administration];molybdenum/pk [Pharmacokinetics];molybdenum/pd [Pharmacology];sulfite;sulfite oxidase/ec [Endogenous Compound];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dt [Drug Therapy];trace element;xanthine dehydrogenase/ec [Endogenous Compound];xanthine oxidase/ec [Endogenous Compound],Anonymous,2006,June,,0,0,
2094,A new mutation of Wilson's disease P-type ATPase gene in a patient with cirrhosis and Coombs-positive hemolytic anemia,,Genotype;Homozygote mutation;Phenotype;Wilson's disease;adult;anamnesis;article;case report;clinical feature;Coombs positive hemolytic anemia/di [Diagnosis];gene mutation;genetic analysis;human;laboratory test;liver cirrhosis;male;ophthalmoscopy;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adenosine triphosphatase;penicillamine/dt [Drug Therapy],"Leggio, L.;Addolorato, G.;Loudianos, G.;Abenavoli, L.;Lepori, M. B.;Vecchio, F. M.;Rapaccini, G. L.;De Virgiliis, S.;Gasbarrini, G.",2006,January,http://dx.doi.org/10.1007/s10620-006-3080-8,0,0,
2095,American Gastroenterological Association Institute Medical Position Statement on the Use of Gastrointestinal Medications in Pregnancy,"This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute on ""Use of Gastrointestinal Medications in Pregnancy."" It was approved by the Clinical Practice and Economics Committee on February 22, 2006, and by the AGA Institute Governing Board on April 20, 2006. © 2006 American Gastroenterological Association Institute.",abdominal pain/dt [Drug Therapy];absence of side effects/si [Side Effect];adrenal insufficiency/si [Side Effect];arthropathy/si [Side Effect];article;birth defect/cn [Congenital Disorder];birth defect/si [Side Effect];blood clotting disorder/si [Side Effect];bradycardia/si [Side Effect];cardiovascular malformation/si [Side Effect];chondropathy/si [Side Effect];cleft lip/si [Side Effect];cleft palate/si [Side Effect];congenital malformation/cn [Congenital Disorder];congenital malformation/si [Side Effect];constipation/dt [Drug Therapy];dehydration/si [Side Effect];diarrhea/dt [Drug Therapy];embryotoxicity/si [Side Effect];enteritis/dt [Drug Therapy];fetotoxicity/si [Side Effect];gastroesophageal reflux/dt [Drug Therapy];gastrointestinal disease/dt [Drug Therapy];gastrointestinal disease/th [Therapy];gastrointestinal endoscopy;gastrointestinal symptom/si [Side Effect];graft rejection/dt [Drug Therapy];graft rejection/pc [Prevention];health care organization;high risk pregnancy;human;hypermagnesemia/si [Side Effect];hyperphosphatemia/si [Side Effect];infectious diarrhea/dt [Drug Therapy];intrauterine growth retardation/si [Side Effect];irritable colon/dt [Drug Therapy];irritable colon/th [Therapy];liver disease;maternal welfare;milk alkali syndrome/si [Side Effect];nausea/dt [Drug Therapy];neonatal hemorrhage/si [Side Effect];neurotoxicity/si [Side Effect];nonhuman;peptic ulcer/dt [Drug Therapy];pregnancy;pregnant woman;premature fetus membrane rupture/si [Side Effect];primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/dt [Drug Therapy];priority journal;risk assessment;sedation;skeleton malformation/si [Side Effect];teratogenesis;teratogenicity/si [Side Effect];treatment withdrawal;unspecified side effect/si [Side Effect];virus hepatitis/dt [Drug Therapy];vomiting/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];wound healing impairment/si [Side Effect];antibiotic agent/ae [Adverse Drug Reaction];antibiotic agent/dt [Drug Therapy];bicarbonate/ae [Adverse Drug Reaction];bismuth/ae [Adverse Drug Reaction];calcium carbonate/ae [Adverse Drug Reaction];calcium carbonate/dt [Drug Therapy];castor oil/ae [Adverse Drug Reaction];cyclosporin/ae [Adverse Drug Reaction];cyclosporin/dt [Drug Therapy];doxycycline/ae [Adverse Drug Reaction];gastrointestinal agent/ae [Adverse Drug Reaction];gastrointestinal agent/dt [Drug Therapy];gastrointestinal agent/to [Drug Toxicity];hepatitis vaccine/dt [Drug Therapy];lamivudine/ae [Adverse Drug Reaction];lamivudine/dt [Drug Therapy];laxative/ae [Adverse Drug Reaction];laxative/dt [Drug Therapy];loperamide/ae [Adverse Drug Reaction];loperamide/dt [Drug Therapy];methotrexate/ae [Adverse Drug Reaction];metoclopramide/dt [Drug Therapy];omeprazole/ae [Adverse Drug Reaction];omeprazole/dt [Drug Therapy];ondansetron/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prochlorperazine/dt [Drug Therapy];promethazine/dt [Drug Therapy];propranolol/ae [Adverse Drug Reaction];propranolol/dt [Drug Therapy];proton pump inhibitor/ae [Adverse Drug Reaction];proton pump inhibitor/dt [Drug Therapy];ribavirin/ae [Adverse Drug Reaction];sodium dihydrogen phosphate;tacrolimus/ae [Adverse Drug Reaction];tacrolimus/dt [Drug Therapy];tetracycline/ae [Adverse Drug Reaction];thalidomide/ae [Adverse Drug Reaction];tricyclic antidepressant agent/ae [Adverse Drug Reaction];tricyclic antidepressant agent/dt [Drug Therapy];trimethobenzamide/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/ae [Adverse Drug Reaction];ursodeoxycholic acid/dt [Drug Therapy],"Mahadevan, U.;Kane, S.",2006,July,http://dx.doi.org/10.1053/j.gastro.2006.04.048,0,0,
2096,Late onset of Wilson's disease in a family with genetic haemochromatosis,"We report the coexistence of Wilson's disease and genetic haemochromatosis in one family. The diagnosis of genetic haemochromatosis was established in a 52-year-old man. Among his siblings, one 57-year-old sister and one 55-year-old brother had decreased copper and ceruloplasmin levels in serum and increased urinary copper excretion. The sister shared the same human leucocyte antigen haplotypes and was homozygous for the HFE mutation C282Y, like the propositus. However, she had normal liver iron content and increased liver copper content. Her dietary copper intake was probably excessive. The association of Wilson's disease and genetic haemochromatosis is rare and has only been described twice. The onset of Wilson's disease after 50 years of age is rare; Wilson's disease should be considered in any patient with unexplained chronic liver disease; an excess in liver copper content might be induced by excessive dietary input in a susceptible individual. © 2006 Lippincott Williams & Wilkins.",Copper;Genetic haemochromatosis;Wilson's disease;adult;anamnesis;article;case report;ceruloplasmin blood level;copper blood level;dietary intake;DNA determination;female;gene mutation;genetic disorder/di [Diagnosis];genetic disorder/dt [Drug Therapy];haplotype;hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];histopathology;homozygosity;human;human tissue;iron storage;laboratory test;liver biopsy;malaise/si [Side Effect];male;onset age;priority journal;urinary excretion;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];HFE protein/ec [Endogenous Compound];HLA antigen/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Dib, N.;Valsesia, E.;Malinge, M. C.;Mauras, Y.;Misrahi, M.;Cales, P.",2006,January,http://dx.doi.org/10.1097/00042737-200601000-00008,0,0,
2097,Pediatric liver transplantation. Introduction of a program for southern Germany in Heidelberg,"Pediatric liver transplantation in Germany is exclusively performed in four centers in the north of Germany. We report our experience with the implementation of a new pediatric liver transplantation program in Heidelberg for children living in the south of Germany. In a pilot phase, we have transplanted eight children with various transplantation techniques including reduced size, left lateral split (segments 2 and 3), and full left split (segments 1-4). All transplantations were successful. No vascular complications occurred. The immunosuppressive regimen we used was cyclosporine A and methylprednisolone. The rate of acute rejection was three of eight patients. No patient required a retransplantation. One patient died due to a severe fungal sepsis he had acquired prior to transplantation. We conclude that in a multidisciplinary approach with careful patient selection a new program for pediatric liver transplantation can be successfully established. © 2006 Blackwell Munksgaard.",Heidelberg;Pediatric liver transplantation;acute graft rejection/co [Complication];acute graft rejection/dt [Drug Therapy];acute graft rejection/pc [Prevention];adolescent;article;child;cholangitis/co [Complication];cholestasis/su [Surgery];clinical article;cytomegalovirus infection/co [Complication];cytomegalovirus infection/dt [Drug Therapy];cytomegalovirus infection/pc [Prevention];death;drug dose regimen;female;Germany;health program;hospital admission;human;immunosuppressive treatment;infant;liver cirrhosis/su [Surgery];liver failure/dt [Drug Therapy];liver failure/si [Side Effect];liver failure/su [Surgery];liver transplantation;male;nonhodgkin lymphoma/dt [Drug Therapy];pediatric surgery;pneumocystosis/co [Complication];pneumocystosis/dt [Drug Therapy];pneumocystosis/pc [Prevention];postoperative infection/co [Complication];postoperative infection/dt [Drug Therapy];postoperative infection/pc [Prevention];priority journal;sepsis;surgical technique;thrombosis/co [Complication];thrombosis/dt [Drug Therapy];thrombosis/pc [Prevention];vascular disease/co [Complication];Wilson disease;acetylsalicylic acid/do [Drug Dose];acetylsalicylic acid/dt [Drug Therapy];ampicillin/cb [Drug Combination];ampicillin/dt [Drug Therapy];basiliximab/cb [Drug Combination];basiliximab/dt [Drug Therapy];cefotaxime/cb [Drug Combination];cefotaxime/dt [Drug Therapy];cotrimoxazole/dt [Drug Therapy];cyclosporin A/cb [Drug Combination];cyclosporin A/dt [Drug Therapy];ganciclovir/dt [Drug Therapy];ganciclovir/iv [Intravenous Drug Administration];ganciclovir/po [Oral Drug Administration];heparin/dt [Drug Therapy];mercaptopurine/ae [Adverse Drug Reaction];mercaptopurine/dt [Drug Therapy];methylprednisolone/cb [Drug Combination];methylprednisolone/do [Drug Dose];methylprednisolone/dt [Drug Therapy];metronidazole/cb [Drug Combination];metronidazole/dt [Drug Therapy];penicillamine/dt [Drug Therapy];sandimmune optoral;tsukubaenolide/dt [Drug Therapy];ursodeoxycholic acid,"Engelmann, G.;Meyburg, J.;Schmidt, J.;Lenhartz, H.",2006,December,http://dx.doi.org/10.1111/j.1399-0012.2006.00611.x,0,0,
2098,Impact of chirality on drug action,"The biological activity of a drug molecule is usually initiated through its interaction with receptors. The effect induced by the drug depends upon the affinity of the drug molecule for its specific receptor. For chiral receptors such as receptor proteins, the chirality of the interacting molecule plays a major role in defining biological activity towards affinity of the molecule for the receptor and subsequent drug action. The biological activity of a racemate in most cases is the contribution of an active enantiomer whereas the other enantiomer may be an undesired commodity. In some cases different enantiomers may possess different activities. Therefore, a recent trend in drug development is the use of the active enantiomer as a drug to avoid unnecessary loading the body with the inactive or undesirable ingredient. To meet this requirement, newer technologies have been developed for chiral separation of molecules.",Chirality;Drug action;Receptor;Review;biological activity;biotransformation;birth defect/si [Side Effect];blindness/si [Side Effect];cleft palate/si [Side Effect];deformity/si [Side Effect];drug mechanism;drug receptor binding;drug structure;enantiomer;hearing impairment/si [Side Effect];human;ligand binding;nonhuman;quantitative structure activity relation;stereochemistry;teratogenicity/si [Side Effect];Wilson disease/dt [Drug Therapy];amfebutamone/pd [Pharmacology];amlodipine/pd [Pharmacology];atropine/an [Drug Analysis];atropine/pd [Pharmacology];candoxatril/pd [Pharmacology];captopril/pd [Pharmacology];centchroman/an [Drug Analysis];centchroman/pd [Pharmacology];cetirizine/pd [Pharmacology];chloramphenicol/pd [Pharmacology];cisapride/pd [Pharmacology];devazepide/pd [Pharmacology];doxazosin/pd [Pharmacology];enalapril/pd [Pharmacology];ezetimibe/pd [Pharmacology];ibuprofen/an [Drug Analysis];ibuprofen/pd [Pharmacology];labetalol/pd [Pharmacology];lercanidipine/pd [Pharmacology];loxiglumide/pd [Pharmacology];naproxen/pd [Pharmacology];omapatrilat/pd [Pharmacology];ondansetron/pd [Pharmacology];oxybutynin/pd [Pharmacology];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pioglitazone/pd [Pharmacology];rosiglitazone/pd [Pharmacology];saquinavir/pd [Pharmacology];sibutramine/pd [Pharmacology];thalidomide/ae [Adverse Drug Reaction];thalidomide/an [Drug Analysis];thalidomide/to [Drug Toxicity];thalidomide/pd [Pharmacology];ticalopride;troglitazone/pd [Pharmacology];unindexed drug;zopiclone/pd [Pharmacology],"Sangita;Ray, S.",2006,April,,0,0,
2099,Morbus Wilson: Case report of a two-year-old child as first manifestation,"Morbus Wilson, or Wilson's disease, is a genetic disease of copper metabolism. Usually the disease is detected when the first clinical symptoms appear, generally not before 5 years of age. This case report shows that the disease can be detected much earlier if abnormal laboratory findings in the patient's history prompt further investigations. © 2006 Taylor & Francis.",Copper metabolism;Liver enzymes;Morbus Wilson;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;case report;cell nucleus;cell ultrastructure;clinical feature;copper blood level;female;gene mutation;heterozygosity;human;lactate dehydrogenase blood level;liver biopsy;liver cell;preschool child;priority journal;symptom;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];copper/ec [Endogenous Compound];glutamate dehydrogenase/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Beyersdorff, A.;Findeisen, A.",2006,March,http://dx.doi.org/10.1080/00365520500389453,0,0,
2100,"The use of tetrathiomolybdate in treating fibrotic, inflammatory, and autoimmune diseases, including the non-obese diabetic mouse model","Tetrathiomolybdate was originally developed for use in Wilson's disease. However, lowering copper levels to below normal levels with tetrathiomolybdate has been found to have efficacy in cancer, probably by turning down signaling by angiogenic cytokines. More recently, we have shown in animals models that tetrathiomolybdate dramatically inhibits pulmonary and liver fibrosis. In other animal models, we have shown that the drug also inhibits liver damage from concanavalin A and acetaminophen, and heart damage from doxorubicin. These studies are briefly reviewed, and we then present data on tetrathiomolybdate's partially protective effect against diabetes in non-obese diabetic mice, an autoimmune model of type I diabetes. Possible mechanisms of tetrathiomolybdate's protective effect are briefly considered. © 2005 Elsevier Inc. All rights reserved.",Copper;Diabetes;Fibrotic disease;Inflammatory diseases;Tetrathiomolybdate;article;autoimmune disease/dt [Drug Therapy];autoimmune disease/pc [Prevention];dose response;drug dose regimen;drug effect;drug efficacy;drug mechanism;drug screening;experimental model;experimental mouse;heart injury/dt [Drug Therapy];heart injury/pc [Prevention];inflammatory disease/dt [Drug Therapy];inflammatory disease/pc [Prevention];insulin dependent diabetes mellitus/dt [Drug Therapy];insulin dependent diabetes mellitus/pc [Prevention];liver fibrosis/dt [Drug Therapy];liver fibrosis/pc [Prevention];liver injury/dt [Drug Therapy];liver injury/pc [Prevention];liver protection;lung fibrosis/dt [Drug Therapy];lung fibrosis/pc [Prevention];mouse strain;nonhuman;bleomycin/to [Drug Toxicity];bleomycin/tl [Intrathecal Drug Administration];carbon tetrachloride;concanavalin A/to [Drug Toxicity];concanavalin A/iv [Intravenous Drug Administration];doxorubicin/to [Drug Toxicity];doxorubicin/ip [Intraperitoneal Drug Administration];paracetamol/to [Drug Toxicity];paracetamol/po [Oral Drug Administration];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology],"Brewer, G. J.;Dick, R.;Zeng, C.;Hou, G.",2006,May,http://dx.doi.org/10.1016/j.jinorgbio.2005.10.007,0,0,
2101,A patient with hemolysis and abnormal liver function tests. [Dutch],"A 22-year-old woman presenting with epigastric pain, anorexia, pronounced asthenia and icterus, was hospitalized. Laboratory data revealed a haemolytic anemia in combination with impaired liver function tests. Abdominal ultrasound displayed no important abnormalities. The clinical presentation, in combination with the biochemical changes, led to a diagnosis of Wilson's disease. Despite its rare occurrence, Wilson's disease should be considered in each patient between five and forty years with an unexplained hepatic or neuropsychiatric symptomatology. Wilson's disease is an autosomal, recessively inherited disorder of copper accumulation, caused by a genetic defect localized on chromosome arm 13q. Its symptomatology, diagnosis, pathogenesis and therapy are discussed. Early recognition and diagnosis are extremely important since they can prevent a severe and permanent tissue damage and death.",abdominal radiography;adult;article;case report;ceruloplasmin blood level;chromosome 13q;chromosome arm;clinical feature;copper blood level;female;hemolysis;hemolytic anemia/di [Diagnosis];histopathology;human;laboratory test;liver biopsy;liver dysfunction/di [Diagnosis];liver function test;nuclear magnetic resonance imaging;pathogenesis;vitamin supplementation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Van Steenkiste, C.;Buydens, P.;Demaeseneer, R.;Van Waes, L.;Debeuckelaere, S.;Reekmans, A.",2006,15 Aug,http://dx.doi.org/10.2143/TVG.62.16.2021570,0,0,
2102,Effects of copper metabolism on neurological functions in Wistar and Wilson's disease model rats,"Behavioral functions of Wistar and Long-Evans Cinnamon (LEC) rats, Wilson's disease animal model, were compared by measuring the open-field, acoustic startle reflex and prepulse inhibition (PPI), and shuttle-box avoidance learning tests with or without oral supplementation with copper or d-penicillamine, copper chelator. All of the LEC rats, irrespective of the treatment, exhibited higher locomotor activity, a decreased habituation to startle response or a lower PPI, compared with Wistar rats. The copper content of all brain regions examined, except for the medulla oblongata of LEC rats, was significantly lower than those in Wistar rats. Besides, in the region of the striatum and the nucleus accumbens of the LEC rats, lower content of norepinephrine, and higher content of dopamine and serotonin were observed compared with Wistar rats. Although copper supplementation did not affect the brain copper content, it reduced the PPI in both Wistar and LEC rats. In contrast, d-penicillamine supplementation decreased both the brain copper content and locomotor activity, and enhanced the startle amplitude only in Wistar rats. These findings suggest that an imbalance in copper homeostasis affects monoamine metabolism and behavioral functions. © 2006 Elsevier Inc. All rights reserved.",Acoustic startle reflex;atp7b;d-Penicillamine;Dopamine;LEC rat;Open-field;Prepulse inhibition;Serotonin;Wilson's disease;acoustic reflex;animal behavior;animal experiment;animal model;animal tissue;article;avoidance behavior;brain function;brain region;bulbar paralysis;controlled study;copper metabolism;corpus striatum;diet supplementation;disease model;homeostasis;locomotion;male;monoamine metabolism;nonhuman;nucleus accumbens;open field behavior;priority journal;rat;rat strain;startle reflex;Wilson disease;chelating agent;copper;monoamine;penicillamine,"Fujiwara, N.;Iso, H.;Kitanaka, N.;Kitanaka, J.;Eguchi, H.;Ookawara, T.;Ozawa, K.;Shimoda, S.;Yoshihara, D.;Takemura, M.;Suzuki, K.",2006,27 Oct,http://dx.doi.org/10.1016/j.bbrc.2006.08.139,0,0,
2103,"Copper in medicine: Homeostasis, chelation therapy and antitumor drug design","As one of the most important essential transition metals, copper is involved in a variety of biological processes such as embryo development, connective tissue formation, temperature control and nerve cell function. It is also related to severe diseases such as Wilson's and Menkes diseases and some neurological disorders. Novel components of copper homeostasis include copper-transporting P-type ATPases, Menkes and Wilson proteins, and copper chaperones in humans have been identified and characterized at the molecular level. These findings have paved the way towards better understanding of the role of copper deficiency or copper toxicity in physiological and pathological conditions. Therefore, organic compounds that can interfere with copper homeostasis may find therapeutic application in copper-dependent diseases. The antitumor activity of copper complexes was reported several decades ago, and many new complexes have demonstrated great antitumor potential. Copper complexes may have relatively lower side effects than platinum-based drugs, and are suggested to be able to overcome inherited or acquired resistance of cisplatin. In this overview, the most recent advances in copper homeostasis, copper-related chelation therapy and design of copper-based antitumor complexes will be summarized. © 2006 Bentham Science Publishers Ltd.","ATP7A protein;Intracellular copper trafficking;Thiosemicarbazone;Trans-Golgi network (TGN);TSC pharmocophore;Wilson's disease (WD);antineoplastic activity;bone disease/si [Side Effect];bone marrow suppression/si [Side Effect];cell function;chelation therapy;clinical trial;connective tissue;copper deficiency;disease association;drug design;drug hypersensitivity/si [Side Effect];embryo development;homeostasis;human;Menkes syndrome/dt [Drug Therapy];nerve cell;neurologic disease;neurotoxicity/si [Side Effect];nonhuman;protein analysis;proteinuria/si [Side Effect];review;stomach discomfort/si [Side Effect];thermoregulation;unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];1,2 naphthaquinone/cb [Drug Combination];1,2 naphthaquinone/cm [Drug Comparison];1,2 naphthaquinone/pd [Pharmacology];10 deacetylbaccatin/cb [Drug Combination];10 deacetylbaccatin/cm [Drug Comparison];10 deacetylbaccatin/pd [Pharmacology];antineoplastic agent/ae [Adverse Drug Reaction];antineoplastic agent/an [Drug Analysis];antineoplastic agent/dv [Drug Development];antineoplastic agent/dt [Drug Therapy];antineoplastic agent/pd [Pharmacology];chaperone/ec [Endogenous Compound];cisplatin;clioquinol/an [Drug Analysis];clioquinol/pd [Pharmacology];copper/ec [Endogenous Compound];copper complex/ae [Adverse Drug Reaction];copper complex/an [Drug Analysis];copper complex/dv [Drug Development];copper complex/dt [Drug Therapy];copper complex/pd [Pharmacology];copper exporting adenosine triphosphatase/ec [Endogenous Compound];dimercaprol/an [Drug Analysis];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];dimercaprol/pd [Pharmacology];hydrazide derivative/an [Drug Analysis];hydrazide derivative/cb [Drug Combination];hydrazide derivative/pd [Pharmacology];Menkes protein/ec [Endogenous Compound];n nicotinoyl n' o hydroxythiobenzhydrazide/an [Drug Analysis];n nicotinoyl n' o hydroxythiobenzhydrazide/cb [Drug Combination];n nicotinoyl n' o hydroxythiobenzhydrazide/pd [Pharmacology];n salicyl n' thiobenzohyrazide/an [Drug Analysis];n salicyl n' thiobenzohyrazide/cb [Drug Combination];n salicyl n' thiobenzohyrazide/pd [Pharmacology];organic compound;paclitaxel/cm [Drug Comparison];penicillamine/ae [Adverse Drug Reaction];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];platinum/ae [Adverse Drug Reaction];platinum/cm [Drug Comparison];prodrug/cb [Drug Combination];prodrug/cm [Drug Comparison];prodrug/pd [Pharmacology];pyridine derivative/an [Drug Analysis];pyridine derivative/cb [Drug Combination];pyridine derivative/cm [Drug Comparison];pyridine derivative/pd [Pharmacology];quinone derivative/cb [Drug Combination];quinone derivative/cm [Drug Comparison];quinone derivative/pd [Pharmacology];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/an [Drug Analysis];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/to [Drug Toxicity];tetrathiomolybdic acid/pd [Pharmacology];thiohydrazide/an [Drug Analysis];thiohydrazide/cb [Drug Combination];thiohydrazide/pd [Pharmacology];thiosemicarbazone derivative/an [Drug Analysis];thiosemicarbazone derivative/dv [Drug Development];thiosemicarbazone derivative/pd [Pharmacology];transition element;trientine/ae [Adverse Drug Reaction];trientine/an [Drug Analysis];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];unclassified drug;unindexed drug;Wilson disease protein/ec [Endogenous Compound];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy];zinc acetate/pd [Pharmacology]","Wang, T.;Guo, Z.",2006,March,http://dx.doi.org/10.2174/092986706776055742,0,0,
2104,Successful plasma exchange treatment in hemolytic crisis of Wilson's disease preventing liver transplantation [1],,adolescent;anamnesis;case report;clinical feature;female;follow up;hemolysis/di [Diagnosis];hemolysis/th [Therapy];hepatitis/di [Diagnosis];human;laboratory test;letter;liver failure/di [Diagnosis];liver transplantation;physical examination;plasmapheresis;priority journal;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Harmanci, O.;Buyukasik, Y.;Bayraktar, Y.",2006,July,http://dx.doi.org/10.1007/s10620-006-8039-2,0,0,
2105,Treatment of Wilson disease with ammonium tetrathiomolybdate - IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease,"Objective: To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery. Design: A randomized, double-blind, controlled, 2-arm study of 48 patients with the neurologic presentation of Wilson disease. Patients either received 500 mg of trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times per day with meals and 20 mg 3 times per day between meals for 8 weeks. All patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8 weeks, with neurologic and speech function assessed weekly; discharged taking 50 mg of zinc 3 times per day, and returned annually for follow-up. Setting: A university hospital referral setting. Patients: Primarily newly diagnosed patients with Wilson disease presenting with neurologic symptoms who had not been treated longer than 4 weeks with an anticopper drug. Intervention: Treatment with either trientine plus zinc or tetrathiomolybdate plus zinc. Main Outcome Measures: Neurologic function was assessed by semiquantitative neurologic and speech examinations. Drug adverse events were evaluated by blood cell counts and biochemical measures. Results: Six of 23 patients in the trientine arm and 1 of 25 patients in the tetrathiomolybdate arm underwent neurologic deterioration (P<.05). Three patients receiving tetrathiomolybdate had adverse effects of anemia and/or leukopenia, and 4 had further transaminase elevations. One patient receiving trientine had an adverse effect of anemia. Four patients receiving trientine died during follow-up, 3 having shown initial neurologic deterioration. Neurologic and speech recovery during a 3-year follow-up period were quite good. Conclusion: Tetrathiomolybdate is a better choice than trientine for preserving neurologic function in patients who present with neurologic disease. ©2006 American Medical Association. All rights reserved.",abnormally high substrate concentration in blood/si [Side Effect];adult;aminotransferase blood level;anemia/si [Side Effect];article;blood cell count;clinical article;clinical trial;controlled clinical trial;controlled study;disease exacerbation/si [Side Effect];double blind procedure;drug safety;female;follow up;hospital patient;human;leukemia/si [Side Effect];leukopenia/si [Side Effect];male;neurologic disease/si [Side Effect];priority journal;randomized controlled trial;speech analysis;time series analysis;treatment duration;university hospital;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/ct [Clinical Trial];tetrathiomolybdate ammonium/cb [Drug Combination];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Brewer, G. J.;Askari, F.;Lorincz, M. T.;Carlson, M.;Schilsky, M.;Kluin, K. J.;Hedera, P.;Moretti, P.;Fink, J. K.;Tankanow, R.;Dick, R. B.;Sitterly, J.",2006,April,http://dx.doi.org/10.1001/archneur.63.4.521,1,1,
2106,Genetic disorders of copper metabolism. [Japanese],"Genetic disorders of copper metabolism in mainly Menkes disease and Wilson disease were reviewed. Menkes disease is caused by a mutation in ATP7A gene, and shows X-linked inheritance. In this disease, copper absorption in the intestine is disturbed, resulting in copper deficiency. The clinical features, including neurological degeneration, connective tissue abnormalities and hair abnormalities, appear at the age of 2-3 months. The serum levels of copper and ceruloplasmin are significantly low while the copper concentration is very high in the cultured fibroblasts. Treatment accepted so far is parenteral administration of copper. When the treatment is started during the neonatal periods, the neurological degeneration could be prevented. Wilson disease, caused by a mutation in ATP7B gene, shows autosomal recessive inheritance and the prevalence rate is high. This disease is associated with the toxic effects of copper accumulated in many tissues, including the liver, brain, kidney and cornea. The serum levels of copper and ceruloplasmin are significantly low, while the copper concentration is very high in the liver. The diagnosis is made by the findings of increased urinary copper excretion and hepatic copper accumulation. The gene analysis is also available for the diagnosis. All the patients should be treated with chelating agents or zinc. However, some patients with neurological disturbances show poor response to these treatments. In addition, these treatments are ineffective in patients with fulminant hepatic failure. Liver transplantation is now accepted in these patients. In these patients also, the disturbances can be prevented by early treatment with chelating agents or zinc. Thus, early diagnosis and treatment are most important for Menkes disease and Wilson disease.",Copper metabolism;Copper-transporting ATPase;Menkes disease;Occipital horn syndrome;Wilson disease;autosomal recessive inheritance;bioaccumulation;brain degeneration;brain tissue;cell culture;ceruloplasmin blood level;clinical feature;connective tissue disease;copper blood level;copper deficiency;cornea;early diagnosis;fibroblast;gene mutation;genetic analysis;genetic disorder/di [Diagnosis];genetic disorder/dt [Drug Therapy];genetic disorder/et [Etiology];genetic disorder/su [Surgery];hair disease;human;inheritance;intestine absorption;kidney parenchyma;liver;liver failure;liver transplantation;Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];prevalence;review;treatment response;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];X chromosome linked disorder/dt [Drug Therapy];X chromosome linked disorder/et [Etiology];chelating agent/dt [Drug Therapy];copper/dt [Drug Therapy];copper/pa [Parenteral Drug Administration];Menkes protein;Wilson disease protein;zinc/dt [Drug Therapy],"Kodama, H.",2006,January,,0,0,
2107,Wilson's disease. [French],"Wilson's disease is an autosomal recessive disorder of copper excess. This illness results from mutations of the ATP7B gene chromosome 13. The discovery of the gene allowed a better understanding of cytosolic copper trafficking its relationship with ceruloplasmin synthesis. Symptomatic patients may present with hepatic, neurologic or psychiatric forms. Clinical and phenotypic evidences provide only presumptive arguments for this disease which can be routinely assessed by molecular analysis. This disease can be efficiently treated by chelation and zinc therapy. Liver transplantation is the therapy to patients with hepatic fulminant course, or in those with relentless progression of hepatic dysfunction in spite of medical therapy.",article;autosomal recessive inheritance;chelation;chromosome 13;computer assisted tomography;copper metabolism;gene mutation;genetic analysis;genotype;human;liver transplantation;molecular genetics;polymerase chain reaction;restriction fragment length polymorphism;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Duclos-Vallee, J. C.;Ichai, P.;Chapuis, P.;Misrahi, M.;Woimant, F.",2006,15 Mar,,0,0,
2108,"A case of woman who was diagnosed as Wilson's disease because of lethe and baldness at 45 years old, who had been diagnosed as idiopathic portal hypertension. [Japanese]","We experienced a 45-years-old woman who could be diagnosed as Wilson's disease. The patient was admitted to our hospital due to general fatigue in 1998 and was diagnosed idiopathic portal hypertension. However, the patient suffered progressive neurological disability from July, 2004 and was admitted to our hospital in August 2005. Laboratory data showed decreased serum ceruloplasmin level, increased 24-hour urine copper level. Liver biopsy showed copper deposits in hepatocytes. The patient was diagnosed as Wilson's disease. Her brother was also diagnosed as Wilson's disease because of copper-related marker, presence of Kayser-Fleisher rings and copper deposits in hepatocytes. Both individuals were treated with D-penicillamine. We suggest that Wilson's disease must be considered in adult patients with nondiagnostic hepatic disease. © 2006 The Japan Society of Hepatology.",adult;alopecia;article;bioaccumulation;case report;ceruloplasmin blood level;fatigue;female;human;idiopathic portal hypertension/di [Diagnosis];laboratory test;liver biopsy;liver cell;neurologic disease;portal hypertension/di [Diagnosis];urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Otsuka, T.;Hagiwara, S.;Tojima, H.;Nagasaka, K.;Tomioka, S.;Ohno, Y.;Makita, F.;Takagi, H.;Mori, M.",2006,,http://dx.doi.org/10.2957/kanzo.47.347,0,0,
2109,Clinical and neuropathological report of Menkes disease. [Chinese],"Objective: To review the clinical and autopsy neuropathological changes of one Menkes disease patient who was misdiagnosed as Wilson disease, and to reveal the clinical and neuropathological differences between these two diseases. Methods and Results: A girl at 8 years old gradually presented lower limb weakness, multiple joint deformities, both hand as claw-like ulnar drift deformity, osteoporosis, extremities lead-pipe rigidity, tremor, dysphasia, and mental retardation. She had high palatal arch, gingival bleeding, nasal hemorrhage and retention of urine, etc. Physical examination: the patient can not complete both hands alternating movement test, heel-knee-tibia test, and finger-nose test, and presented pyramidal sign. Laboratory examination: serum ceruloplasmin was 0.02 mumol/L. Clinical diagnosis: hepatolenticular degeneration (also called Wilson disease) complicated with osteopathy. Treated with D-penicillamine (0.3 g) oral administration 3/d. Signs and symptoms progressively deteriorated. She died at 16 years old. Autopsy neuropathological results: cerebral parenchyma presented extensive atrophy, bilateral subcortical white matter of the frontoparietal lobe showed severe atrophy, degeneration and cavitation. Optical microscopic observation: Obvious changes in basal ganglion tissue were not seen. Irregular vascular lumen and endangium shrinkage may be occasionally found. In the cortex neurons of granular cell layer reduced obviously, and white matter showed extensive demyelinated degeneration with vesiculation. Massive astrocytes, phagocytes, ectopic neurons, and satellite cells proliferated, without perivascular inflammatory cells infiltration. Neuron loss and necrosis were not seen in the head of caudate nucleus, putamen, globus pallidus, and thalamus, but satellite cells around the neurons were markedly increased. There were many activated microgliocytes. Deposit could be found in the neurons at the tail of caudate nucleus. No Opaski cells and Alzheimer type II cells were seen. The characteristic changes in cerebellum were as follow: residual Purkinje cells presented obvious abnormal dendritic arborization (so called ""weeping willow""), increased perisomatic processes, and focal axonal swelling (""torpedoes""); and Purkinje cells deposited in the granular cell layer. Conclusion: 1) Menkes disease could be seen in females and could onset at childhood or early adult. 2) There are prominent massive white matter degeneration, necrosis, and cavitation. The construction of basal ganglia which remains quite well is inconsistent with the clinical signs and symptoms. Neurons markedly reduced in cortex granular cell layer. Purkinje cells of cerebellum emerge abnormal dendritic arborization. All of these are the characteristic presentations of Menkes disease.","Hereditary diseases;Kinky hair syndrome;Metabolic diseases;Neurologic manifestations;Pathology, clinical;adolescent;arthropathy;astrocyte;autopsy;basal ganglion;brain atrophy;brain cell;brain degeneration;brain region;cell infiltration;demyelination;diagnostic error;dysphasia;epistaxis;gingiva bleeding;granular cell;human;human tissue;inflammation;laboratory test;leg;male;Menkes syndrome;mental deficiency;microscopy;muscle weakness;necrosis;neuropathology;osteopathic medicine;osteoporosis;palate;phagocyte;physical examination;Purkinje cell;pyramidal sign;review;rigidity;satellite cell;tremor;ulna;urine retention;white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration]","Gao, J.;Guo, Y. P.;Gao, S. F.;Zhang, Z. X.;Huang, H. F.;Ren, H. T.;Zhao, Y. H.",2006,June,,0,0,
2110,Are rare diseases still orphans or happily adopted? The challenges of developing and using orphan medicinal products,"Orphan medicinal products (OMPs) are targeted at the diagnosis, prevention or treatment of rare diseases and have a special status in European law. This status brings incentives for pharmaceutical companies to invest in OMP development. The goal of the legislation is to encourage the development of more treatments for life-threatening rare disorders, but increased availability of OMPs raises important issues surrounding the public funding of very expensive treatments by national health services. In this article we review OMPs and the incentives for their development and discuss the challenges presented by funding these treatments. © 2006 Blackwell Publishing Ltd.",Orphan disease;Orphan medicinal product;Rare disease;Ultra orphan disease;adenomatous polyp/dm [Disease Management];adenomatous polyp/dt [Drug Therapy];adrenal cortex carcinoma/dm [Disease Management];adrenal cortex carcinoma/dt [Drug Therapy];Barrett esophagus/dm [Disease Management];Barrett esophagus/dt [Drug Therapy];budget;chronic myeloid leukemia/dm [Disease Management];chronic myeloid leukemia/dt [Drug Therapy];chronic pain/dm [Disease Management];chronic pain/dt [Drug Therapy];cost effectiveness analysis;drug approval;drug cost;drug indication;drug industry;drug marketing;Europe;Fabry disease/dm [Disease Management];Fabry disease/dt [Drug Therapy];gastrointestinal stromal tumor/dm [Disease Management];gastrointestinal stromal tumor/dt [Drug Therapy];Gaucher disease/dm [Disease Management];Gaucher disease/dt [Drug Therapy];glycogen storage disease type 2/dm [Disease Management];glycogen storage disease type 2/dt [Drug Therapy];health service;human;Hunter syndrome/dm [Disease Management];Hunter syndrome/dt [Drug Therapy];law;mucopolysaccharidosis/dm [Disease Management];mucopolysaccharidosis/dt [Drug Therapy];Niemann Pick disease/dm [Disease Management];Niemann Pick disease/dt [Drug Therapy];nonhodgkin lymphoma/dm [Disease Management];nonhodgkin lymphoma/dt [Drug Therapy];patent ductus arteriosus/dm [Disease Management];patent ductus arteriosus/dt [Drug Therapy];priority journal;promyelocytic leukemia/dm [Disease Management];promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dm [Disease Management];pulmonary hypertension/dt [Drug Therapy];quality adjusted life year;review;Sandhoff disease/dm [Disease Management];Sandhoff disease/dt [Drug Therapy];thrombocythemia/dm [Disease Management];thrombocythemia/dt [Drug Therapy];thromboembolism/dm [Disease Management];thromboembolism/dt [Drug Therapy];tyrosinemia/dm [Disease Management];tyrosinemia/dt [Drug Therapy];Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/pe [Pharmacoeconomics];agalsidase beta/dt [Drug Therapy];agalsidase beta/pe [Pharmacoeconomics];alpha glucosidase/dt [Drug Therapy];alpha glucosidase/pe [Pharmacoeconomics];anagrelide/dt [Drug Therapy];anagrelide/pe [Pharmacoeconomics];arsenic trioxide/dt [Drug Therapy];arsenic trioxide/pe [Pharmacoeconomics];bosentan/dt [Drug Therapy];bosentan/pe [Pharmacoeconomics];busulfan/dt [Drug Therapy];busulfan/iv [Intravenous Drug Administration];busulfan/pe [Pharmacoeconomics];carglumic acid/dt [Drug Therapy];carglumic acid/pe [Pharmacoeconomics];celecoxib/dt [Drug Therapy];celecoxib/pe [Pharmacoeconomics];cladribine/dt [Drug Therapy];cladribine/pe [Pharmacoeconomics];ibuprofen/dt [Drug Therapy];ibuprofen/pe [Pharmacoeconomics];iduronate 2 sulfatase/dt [Drug Therapy];iduronate 2 sulfatase/pe [Pharmacoeconomics];iloprost/dt [Drug Therapy];iloprost/pe [Pharmacoeconomics];imatinib/dt [Drug Therapy];imatinib/pe [Pharmacoeconomics];imiglucerase/dt [Drug Therapy];imiglucerase/pe [Pharmacoeconomics];laronidase/dt [Drug Therapy];laronidase/pe [Pharmacoeconomics];litak;miglustat/dt [Drug Therapy];miglustat/pe [Pharmacoeconomics];mitotane/dt [Drug Therapy];mitotane/pe [Pharmacoeconomics];nitisinone/dt [Drug Therapy];nitisinone/pe [Pharmacoeconomics];ogt 923/dt [Drug Therapy];ogt 923/pe [Pharmacoeconomics];omega conotoxin MVIIA/dt [Drug Therapy];omega conotoxin MVIIA/sp [Intraspinal Drug Administration];omega conotoxin MVIIA/pe [Pharmacoeconomics];orphan drug/dt [Drug Therapy];orphan drug/pe [Pharmacoeconomics];pegvisomant/dt [Drug Therapy];pegvisomant/pe [Pharmacoeconomics];photofrin/dt [Drug Therapy];photofrin/pe [Pharmacoeconomics];sildenafil/dt [Drug Therapy];sildenafil/pe [Pharmacoeconomics];unclassified drug;wilzin;zinc acetate/dt [Drug Therapy];zinc acetate/pe [Pharmacoeconomics],"Dear, J. W.;Lilitkarntakul, P.;Webb, D. J.",2006,September,http://dx.doi.org/10.1111/j.1365-2125.2006.02654.x,0,0,
2111,Poor cognitive development and abdominal pain: Wilson's disease,"An 8-year-old boy was referred to our hospital because of learning disabilities. His general cognitive functions were below the level for age, and he was diagnosed with dysphasia. The boy was transferred to a special class for children with learning problems. Three months later he was again referred to us because of acute epigastric pain. The only abnormal laboratory finding was a slightly elevated level of alanine aminotransferase. Although the symptoms disappeared in a few days, the transaminase levels remained above normal for the next 6 months. Further diagnostic work-up revealed low serum ceruloplasmin concentration and high 24-h urinary copper excretion. The hepatic copper concentration in liver biopsy was high (2900 mug/g dry weight), confirming the diagnosis of Wilson's disease. Brain MRI showed slight changes in white matter. The patient's asymptomatic sister was also diagnosed with Wilson's disease. Both siblings started penicillamine therapy and a copper-restricted diet. The copper content of the household water was found to be above average and a new plumbing system was installed. After 1 year from the initiation of the therapy, the transaminase concentrations normalized and both siblings were free of symptoms. After 2 years of therapy the patient was able to return to normal school. Wilson's disease must be borne in mind, when children are evaluated because of poor school performance, especially if they complain of abdominal symptoms. © 2006 Taylor & Francis.",Dysphasia;Learning disabilities;Wilson's disease;abdominal pain;academic achievement;alanine aminotransferase blood level;article;case report;ceruloplasmin blood level;child;cognitive development;concentration (parameters);diagnostic procedure;diet restriction;epigastric pain;follow up;household;human;learning disorder;liver biopsy;male;nuclear magnetic resonance imaging;organ weight;patient referral;priority journal;school;sibling;symptom;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alanine aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/to [Drug Toxicity];penicillamine/dt [Drug Therapy];water,"Gronlund, J.;Nanto-Salonen, K.;Venetoklis, J.;Holmberg, R. L.;Heinonen, A.;Stahlberg, M. R.",2006,March,http://dx.doi.org/10.1080/00365520510023431,0,0,
2112,Two unusual cases with Wilson's disease: Hepatoma and fulminant hepatitis treated with plasma exchange,"We report two atypical cases of Wilson's disease. The first case is a 22-year-old male patient with a history of disease for 15 years and diagnosed as Wilson's disease upon investigations. Alpha-fetoprotein level was found elevated and computed tomography showed a 3.5-cm liver mass. Hepatocellular carcinoma was diagnosed. Radiofrequency ablation and liver transplantation were performed successfully. The second case is a 24-year-old female patient who presented with fulminant hepatitis. Urinary copper excretion and ceruloplasmin levels were suggestive of Wilson's disease. Despite chelation therapy, no improvement was observed. Plasma exchange therapy was performed for seven days. Her clinical status improved, and transplantation was no longer needed. To conclude, although hepatoma is rarely seen in Wilson's disease, patients should be examined regularly to diagnose it in a treatable stage. Removal of copper and toxic metabolites with plasma exchange therapy may be a way of treatment for fulminant hepatitis associated with Wilson's disease.",Hepatocellular carcinoma;Plasma exchange;Wilson's disease;adult;anemia;article;brain disease;case report;clinical feature;diagnostic approach route;esophagus varices;female;hepatitis/dt [Drug Therapy];hepatitis/th [Therapy];hepatobiliary scintiscanning;histopathology;human;laboratory test;liver biopsy;liver cell carcinoma/rt [Radiotherapy];liver cell carcinoma/th [Therapy];liver transplantation;male;nuclear magnetic resonance imaging;physical examination;plasmapheresis;priority journal;splenomegaly;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];alpha fetoprotein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Aydinli, M.;Harmanci, O.;Ersoy, O.;Iskit, A. T.;Ozcebe, O.;Abbasoglu, O.;Bayraktar, Y.",2006,December,,0,0,
2113,Psychosis and Wilson's disease: A case report,"In this article we present a case of a 26-year-old woman with clinical picture of acute psychosis, as the first and main manifestation of Wilson's disease, who developed abnormal involuntary choreoathetoid limb movements, few days after initiation of neuroleptic therapy. At the first movement neurological symptoms were misinterpreted as side effect of haloperidol, but consulted neurologist suggested additional diagnostic procedure which confirmed Wilson's disease. Psychiatric symptomatology and abnormal involuntary movements were the clinical manifestation of this disease, which improved with neuroleptic and chelating treatment. Interdisciplinary approach with good collaboration of psychiatrists and neurologists is crucial for Wilson's disease, because early diagnosis and treatment without delay is critical to the prognosis. This case serves as a reminder that involuntary movements can be side effect of antipsychotics but also the clinical manifestation of some illnesses, for example Wilson's, Huntington's and Fuhr's diseases. © Medicinska naklada - Zagreb, Croatia.",Chelation therapy;Cooper;Involuntary movement;Neuroleptics;Psychosis;Wilson's disease;adult;article;blood analysis;case report;choreoathetosis/dt [Drug Therapy];choreoathetosis/si [Side Effect];clinical feature;computer assisted tomography;consultation;cooperation;diagnostic procedure;differential diagnosis;early diagnosis;echography;electroencephalography;female;human;Huntington chorea/di [Diagnosis];limb movement;liver biopsy;medical error;medical specialist;neurology;nuclear magnetic resonance imaging;paranoid psychosis/dt [Drug Therapy];prognosis;psychiatrist;symptomatology;urinalysis;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];haloperidol/ae [Adverse Drug Reaction];haloperidol/dt [Drug Therapy];haloperidol/po [Oral Drug Administration];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];neuroleptic agent/po [Oral Drug Administration];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];pyridoxine/po [Oral Drug Administration],"Jukic, I.;Titlic, M.;Tonkic, A.;Dodig, G.;Rogosic, V.",2006,June,,0,0,
2114,Inherited metabolic liver disease,"PURPOSE OF REVIEW: The past decade has seen understanding of the molecular machinery involved in the pathogenesis of genetic hemochromatosis, Wilson's disease, and alpha1-antitrypsin deficiency grow significantly. This year has seen further progress in elaborating the molecular biology, genetics, epidemiology, and management of these inherited metabolic diseases. RECENT FINDINGS: Both Wilson's disease and genetic hemochromatosis involve defects in the transport of heavy metals and their accumulation in hepatocytes. In alpha1-antitrypsin deficiency, intrahepatocyte accumulation of defective alpha1-antitrypsin occurs. As a more complete picture of the molecular biology of proteins and genes involved in transport has evolved, so has our understanding of their interactions. The molecular genetics of these diseases explains the different phenotypes seen. Finally, the elucidation of the molecular pathophysiology of these diseases has led to new ideas in their clinical management. SUMMARY: The recent developments detailed in this article have important implications for the future. Recent research has elegantly shifted the paradigm in our understanding to one focused on defects in the genetic machinery of the cell and on how better comprehension of these defects can lead to potential new therapies. © 2006 Lippincott Williams & Wilkins.",alpha<inf>1</inf>-antitrypsin;Ceruloplasmin;Copper;Hemochromatosis;Hepcidin;hfe;Iron;Wilson's disease;albumin dialysis;alpha antitrypsin deficiency;copper metabolism;cutis laxa/si [Side Effect];elastosis/dt [Drug Therapy];elastosis/si [Side Effect];gene interaction;hemochromatosis/et [Etiology];human;liver cell;liver cell carcinoma;liver disease/dt [Drug Therapy];liver disease/et [Etiology];metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];molecular biology;molecular genetics;nonhuman;phenotype;protein interaction;pseudoxanthoma elasticum/dt [Drug Therapy];review;skin manifestation/dt [Drug Therapy];skin manifestation/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha 1 antitrypsin/ec [Endogenous Compound];calcimycin;heavy metal;hepcidin/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];retinoid/dt [Drug Therapy];steroid/dt [Drug Therapy];trientine/dt [Drug Therapy];tunicamycin;zinc/dt [Drug Therapy],"Schilsky, M. L.;Fink, S.",2006,May,http://dx.doi.org/10.1097/01.mog.0000218957.63311.0e,0,0,
2115,Orphan medicinal products: Assessment after 5 years of European legislation. [French],,acromegaly/dt [Drug Therapy];acromegaly/ep [Epidemiology];adenomatous polyp/dt [Drug Therapy];adenomatous polyp/ep [Epidemiology];cataplexy/dt [Drug Therapy];cataplexy/ep [Epidemiology];chronic pain/dt [Drug Therapy];chronic pain/ep [Epidemiology];cystic fibrosis/dt [Drug Therapy];cystic fibrosis/ep [Epidemiology];drug industry;drug legislation;drug manufacture;Europe;Fabry disease/cn [Congenital Disorder];Fabry disease/dt [Drug Therapy];Fabry disease/ep [Epidemiology];gastrointestinal stromal tumor/dt [Drug Therapy];gastrointestinal stromal tumor/ep [Epidemiology];Gaucher disease/cn [Congenital Disorder];Gaucher disease/dt [Drug Therapy];Gaucher disease/ep [Epidemiology];glioma/dt [Drug Therapy];glioma/ep [Epidemiology];human;Hurler syndrome/cn [Congenital Disorder];Hurler syndrome/dt [Drug Therapy];Hurler syndrome/ep [Epidemiology];hyperammonemia/co [Complication];hyperammonemia/dt [Drug Therapy];hyperammonemia/ep [Epidemiology];immunopathology/dt [Drug Therapy];immunopathology/ep [Epidemiology];infection/dt [Drug Therapy];infection/ep [Epidemiology];leukemia/dt [Drug Therapy];leukemia/ep [Epidemiology];lymphoma/dt [Drug Therapy];lymphoma/ep [Epidemiology];metabolic disorder/dt [Drug Therapy];metabolic disorder/ep [Epidemiology];neurologic disease/dt [Drug Therapy];neurologic disease/ep [Epidemiology];neuromuscular disease/dt [Drug Therapy];neuromuscular disease/ep [Epidemiology];pulmonary hypertension/dt [Drug Therapy];pulmonary hypertension/ep [Epidemiology];review;thrombocythemia/dt [Drug Therapy];thrombocythemia/ep [Epidemiology];tyrosinemia/dt [Drug Therapy];tyrosinemia/ep [Epidemiology];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];agalsidase alfa/dt [Drug Therapy];agalsidase beta/dt [Drug Therapy];anagrelide/dt [Drug Therapy];arsenic trioxide/dt [Drug Therapy];bosentan/dt [Drug Therapy];busulfan/dt [Drug Therapy];carglumic acid/dt [Drug Therapy];celecoxib/dt [Drug Therapy];cladribine/dt [Drug Therapy];ibuprofen/dt [Drug Therapy];iloprost/dt [Drug Therapy];imatinib/dt [Drug Therapy];laronidase/dt [Drug Therapy];litak;miglustat/dt [Drug Therapy];mitotane/dt [Drug Therapy];nitisinone/dt [Drug Therapy];omega conotoxin MVIIA/dt [Drug Therapy];orphan drug/dt [Drug Therapy];orphan drug/pe [Pharmacoeconomics];oxybate sodium/dt [Drug Therapy];pegvisomant/dt [Drug Therapy];photofrin/dt [Drug Therapy];sildenafil/dt [Drug Therapy];unclassified drug;wilzin;zinc acetate/dt [Drug Therapy],"Borensztein, P.",2006,January,,0,0,
2116,Comparison of lowering copper levels with tetrathiomolybdate and zinc on mouse tumor and doxorubicin models,"Tetrathiomolybdate (TM), presumably by lowering copper levels and availability, has shown excellent efficacy in animal models of cancer and models of injury that produce fibrotic or inflammatory damage in lung, heart, and liver. Trials in human patients are underway. If the efficacy of TM is indeed through lowering copper levels, other anticopper drugs should be equally efficacious. Zinc is an anticopper drug, with proven efficacy in Wilson's disease, a disease of copper toxicity. In this study, the efficacy of zinc is compared with TM on a mouse tumor model and on the doxorubicin model of heart damage, and it is hypothesized that when copper availability is lowered to an equivalent extent, the 2 drugs would show equivalent efficacy. No effect is found of zinc on inhibiting growth of a tumor that is markedly inhibited by TM, and zinc is found to be less effective than TM in inhibiting cardiac damage from doxorubicin. This study shows that TM's mechanism of action in protecting against doxorubicin toxicity is because of its anticopper effects, as copper supplementation eliminated the protective effect of TM. It is also hypothesized that the differences between TM and zinc may be caused by TM's mechanism of action in which it binds copper already in the body, whereas zinc does not. © 2006 Mosby, Inc. All rights reserved.",animal cell;animal experiment;animal model;article;cancer inhibition;controlled study;drug binding;drug efficacy;drug mechanism;heart injury/dt [Drug Therapy];heart injury/pc [Prevention];male;mouse;nonhuman;priority journal;protection;tumor/dt [Drug Therapy];tumor model;copper/to [Drug Toxicity];doxorubicin/to [Drug Toxicity];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration];tetrathiomolybdic acid/pd [Pharmacology];zinc/ad [Drug Administration];zinc/cm [Drug Comparison];zinc/dt [Drug Therapy];zinc/pd [Pharmacology];zinc carbonate,"Hou, G.;Dick, R.;Zeng, C.;Brewer, G. J.",2006,December,http://dx.doi.org/10.1016/j.trsl.2006.06.005,0,0,
2117,Drug interactions,,blurred vision/si [Side Effect];combination chemotherapy;confusion/si [Side Effect];consciousness disorder/dt [Drug Therapy];coordination disorder/si [Side Effect];cyanide poisoning/dt [Drug Therapy];diet supplementation;drug absorption;drug alcohol interaction;drug antagonism;drug blood level;drug distribution;drug excretion;drug fatality/si [Side Effect];drug interaction;drug mechanism;drug metabolism;drug overdose;drug potentiation;drug response;drug toxicity;drug transport;fever/si [Side Effect];heat stroke/si [Side Effect];heavy metal poisoning/dt [Drug Therapy];human;hyperglycemia/si [Side Effect];hyperreflexia/si [Side Effect];hypomania/si [Side Effect];immunostimulation;intoxication/dt [Drug Therapy];iron overload/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];monotherapy;motion sickness/dt [Drug Therapy];myoclonus/si [Side Effect];nephrotoxicity/si [Side Effect];ototoxicity/si [Side Effect];pharmacodynamics;priority journal;psychosis/si [Side Effect];review;rheumatoid arthritis/dt [Drug Therapy];sedation;serotonin syndrome/si [Side Effect];side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];xerostomia/si [Side Effect];alcohol/ae [Adverse Drug Reaction];alcohol/cb [Drug Combination];alcohol/it [Drug Interaction];alcohol/dt [Drug Therapy];amitriptyline/ae [Adverse Drug Reaction];amitriptyline/cb [Drug Combination];amitriptyline/it [Drug Interaction];amitriptyline/pd [Pharmacology];antidiabetic agent/it [Drug Interaction];benzodiazepine derivative/ae [Adverse Drug Reaction];benzodiazepine derivative/cb [Drug Combination];benzodiazepine derivative/cr [Drug Concentration];benzodiazepine derivative/do [Drug Dose];benzodiazepine derivative/it [Drug Interaction];benzodiazepine derivative/dt [Drug Therapy];benzodiazepine derivative/pk [Pharmacokinetics];cobalt edetate/ae [Adverse Drug Reaction];cobalt edetate/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];deferoxamine/pd [Pharmacology];Echinacea extract/it [Drug Interaction];edetate calcium disodium/dt [Drug Therapy];edetate calcium disodium/pd [Pharmacology];etacrynic acid/ae [Adverse Drug Reaction];etacrynic acid/cb [Drug Combination];etacrynic acid/it [Drug Interaction];flumazenil/it [Drug Interaction];flumazenil/dt [Drug Therapy];furosemide/ae [Adverse Drug Reaction];furosemide/cb [Drug Combination];furosemide/it [Drug Interaction];ginger extract/it [Drug Interaction];ginseng extract/it [Drug Interaction];glucocorticoid/ae [Adverse Drug Reaction];glucocorticoid/it [Drug Interaction];histamine H1 receptor antagonist/cb [Drug Combination];histamine H1 receptor antagonist/it [Drug Interaction];histamine H1 receptor antagonist/dt [Drug Therapy];monoamine oxidase inhibitor/ae [Adverse Drug Reaction];monoamine oxidase inhibitor/cb [Drug Combination];muscarinic receptor blocking agent/ae [Adverse Drug Reaction];muscarinic receptor blocking agent/cb [Drug Combination];muscarinic receptor blocking agent/it [Drug Interaction];naloxone/it [Drug Interaction];naloxone/dt [Drug Therapy];opiate/do [Drug Dose];opiate/it [Drug Interaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pethidine/ae [Adverse Drug Reaction];pethidine/cb [Drug Combination];serotonin agonist/ae [Adverse Drug Reaction];serotonin agonist/pd [Pharmacology];streptomycin/ae [Adverse Drug Reaction];streptomycin/cb [Drug Combination];streptomycin/it [Drug Interaction];sulfonamide/cb [Drug Combination];sulfonamide/it [Drug Interaction];sulfonamide/pd [Pharmacology];tetracycline/pd [Pharmacology];thioridazine/ae [Adverse Drug Reaction];thioridazine/cb [Drug Combination];thioridazine/it [Drug Interaction];thioridazine/pd [Pharmacology];tobramycin/ae [Adverse Drug Reaction];tobramycin/cb [Drug Combination];tobramycin/it [Drug Interaction];tricyclic antidepressant agent/ae [Adverse Drug Reaction];tricyclic antidepressant agent/cb [Drug Combination];tricyclic antidepressant agent/it [Drug Interaction];trimethoprim/cb [Drug Combination];trimethoprim/it [Drug Interaction];trimethoprim/pd [Pharmacology];unindexed drug,"Pleuvry, B. J.",2006,October,http://dx.doi.org/10.1053/j.mpfou.2006.06.001,0,0,
2118,European and French pharmaceutical market assessed by Prescrire in 2005: Mainly bogus innovation,,acne/si [Side Effect];breast cancer/dt [Drug Therapy];cardiotoxicity/si [Side Effect];cardiovascular disease/si [Side Effect];chickenpox/dt [Drug Therapy];chickenpox/pc [Prevention];clinical trial;decision making;dizziness/si [Side Effect];drug hypersensitivity/si [Side Effect];drug industry;drug marketing;editorial;fatigue/si [Side Effect];gastrointestinal symptom/si [Side Effect];hematologic disease/si [Side Effect];hepatitis/si [Side Effect];human;hypersensitivity reaction/si [Side Effect];hypomagnesemia/si [Side Effect];immune deficiency;interstitial pneumonia/si [Side Effect];leukopenia/si [Side Effect];liver disease/si [Side Effect];mass immunization;nausea/si [Side Effect];neutropenia/si [Side Effect];pleura mesothelioma/dt [Drug Therapy];skin cancer/si [Side Effect];skin infection/si [Side Effect];skin manifestation/si [Side Effect];suicide attempt/si [Side Effect];thrombocytopenia/si [Side Effect];unspecified side effect/si [Side Effect];Wilson disease/dt [Drug Therapy];abacavir/cb [Drug Combination];adalimumab/ae [Adverse Drug Reaction];amprenavir phosphate;aripiprazole;bortezomib;celecoxib/ae [Adverse Drug Reaction];celecoxib/cm [Drug Comparison];cetuximab/ae [Adverse Drug Reaction];cetuximab/dt [Drug Therapy];chickenpox vaccine/ae [Adverse Drug Reaction];chickenpox vaccine/dt [Drug Therapy];cisplatin/ct [Clinical Trial];cisplatin/cb [Drug Combination];cisplatin/cm [Drug Comparison];cisplatin/dt [Drug Therapy];cytarabine;dactinomycin/ae [Adverse Drug Reaction];docetaxel/cb [Drug Combination];docetaxel/cm [Drug Comparison];docetaxel/dt [Drug Therapy];duloxetine/ae [Adverse Drug Reaction];duloxetine/dt [Drug Therapy];efalizumab/ae [Adverse Drug Reaction];fulvestrant;ibritumomab tiuxetan;infliximab/ae [Adverse Drug Reaction];insulin glargine;lamivudine/cb [Drug Combination];miglustat;monoclonal antibody/ae [Adverse Drug Reaction];nonsteroid antiinflammatory agent/cm [Drug Comparison];pemetrexed/ae [Adverse Drug Reaction];pemetrexed/ct [Clinical Trial];pemetrexed/cb [Drug Combination];pemetrexed/cm [Drug Comparison];pemetrexed/dt [Drug Therapy];pramipexole;pregabalin;strontium ranelate;tolcapone/dt [Drug Therapy];trastuzumab/ae [Adverse Drug Reaction];trastuzumab/ct [Clinical Trial];trastuzumab/cb [Drug Combination];trastuzumab/cm [Drug Comparison];trastuzumab/dt [Drug Therapy];unindexed drug;wilzin;zinc acetate/dt [Drug Therapy],Anonymous,2006,March/April,http://dx.doi.org/10.1016/S1130-6343%2806%2973949-6,0,0,
2119,Metabolic liver diseases. [Croatian],"The most common metabolic liver diseases are Wilson's disease (WD), hemochromatosis and alpha-1 antitrypsin deficiency. WD is an autosomal recessive disorder of copper metabolism leading to its accumulation in the body which results in a number of possible hepatic, neurological and psychiatric sequelae. Hemochromatosis is the most common genetic disease in white persons of northern European descent The features of iron overload are often unrecognized and diagnosed only in the setting of advanced disease. If left untreated, WD and hemochromatosis are a fatal conditions. On the other hand, patients detected early and treated with copper/iron reduction therapy, including penicillamine/phlebotomy, can have a normal life expectancy. Given the genetic basis of the condition it is vital that counselling and screening of the patient's first-degree relatives be carried out. Alpha-1 antitrypsin deficiency is the most common metabolic liver disesae in childhood. There is currently no specific treatment for alpha-1 antitrypsin deficiency, although researchers are exploring different techniques of possible gene therapy.",Alpha-1 antitrypsin deficiency;Hemochromatosis;Metabolic liver diseases;Wilson's disease;clinical feature;copper metabolism;Europe;gene therapy;genetic counseling;genetic disorder;genetic screening;hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/et [Etiology];hemochromatosis/pc [Prevention];hemochromatosis/su [Surgery];human;iron overload;life expectancy;liver transplantation;mental disease;neurologic disease;pathogenesis;phlebotomy;prognosis;protein deficiency/di [Diagnosis];protein deficiency/et [Etiology];protein deficiency/pc [Prevention];protein deficiency/su [Surgery];review;vein puncture;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/pc [Prevention];Wilson disease/su [Surgery];alpha 1 antitrypsin/ec [Endogenous Compound];ferritin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];transferrin/dt [Drug Therapy],"Kalauz, M.;Premuzic, M.",2006,,,0,0,
2120,X-ray fluorescence microprobe imaging in biology and medicine,"Characteristic X-ray fluorescence is a technique that can be used to establish elemental concentrations for a large number of different chemical elements simultaneously in different locations in cell and tissue samples. Exposing the samples to an X-ray beam is the basis of X-ray fluorescence microscopy (XFM). This technique provides the excellent trace element sensitivity; and, due to the large penetration depth of hard X-rays, an opportunity to image whole cells and quantify elements on a per cell basis. Moreover, because specimens prepared for XFM do not require sectioning, they can be investigated close to their natural, hydrated state with cryogenic approaches. Until several years ago, XFM was not widely available to bio-medical communities, and rarely offered resolution better then several microns. This has changed drastically with the development of third-generation synchrotrons. Recent examples of elemental imaging of cells and tissues show the maturation of XFM imaging technique into an elegant and informative way to gain insight into cellular processes. Future developments of XFM - building of new XFM facilities with higher resolution, higher sensitivity or higher throughput will further advance studies of native elemental makeup of cells and provide the biological community including the budding area of bionanotechnology with a tool perfectly suited to monitor the distribution of metals including nanovectors and measure the results of interactions between the nanovectors and living cells and tissues. © 2006 Wiley-Liss, Inc.",Bionanotechnology;Elemental maps;Metalome;X-ray fluorescence microscopy;Alzheimer disease/di [Diagnosis];Alzheimer disease/et [Etiology];autoimmune disease/di [Diagnosis];autoimmune disease/et [Etiology];bacterial infection/et [Etiology];biology;biotechnology;breast cancer/et [Etiology];cancer chemotherapy;cancer risk;cell differentiation;cell organelle;cell strain HL 60;cellular distribution;chemical carcinogenesis;cigarette smoking;dietary intake;drug transformation;environmental exposure;esophagus cancer/et [Etiology];fluorescence microscopy;genetic engineering;heavy metal poisoning/di [Diagnosis];heavy metal poisoning/et [Etiology];host pathogen interaction;human;imaging system;implant;leishmaniasis/dr [Drug Resistance];malaria/dr [Drug Resistance];marine environment;medical technology;Menkes syndrome/di [Diagnosis];Menkes syndrome/et [Etiology];metal binding;mitochondrion;molecular imaging;mutagenesis;nanotechnology;neuropathology;nonhuman;osteolysis;osteoporosis/di [Diagnosis];priority journal;prostate cancer/et [Etiology];proteomics;review;squamous cell carcinoma/et [Etiology];stem cell;synchrotron;tissue distribution;tuberculosis/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];X ray fluorescence;X ray fluorescence microscopy;X ray microanalysis;aluminum;antidiabetic agent/pk [Pharmacokinetics];antiinflammatory agent/pk [Pharmacokinetics];antileishmanial agent/dv [Drug Development];antileishmanial agent/pd [Pharmacology];antineoplastic agent/pk [Pharmacokinetics];antiparasitic agent/dv [Drug Development];antiparasitic agent/pd [Pharmacology];arsenic;binding protein;cadmium;calcium;chlorine;chromium;copper;dna;iron;lead;manganese;mercury;metal;nickel;phosphorus;potassium;sulfur;titanium;titanium dioxide;trace element;vanadium;zinc,"Paunesku, T.;Vogt, S.;Maser, J.;Lai, B.;Woloschak, G.",2006,15 Dec,http://dx.doi.org/10.1002/jcb.21047,0,0,
2121,Wilson's disease: An update for clinical biochemists,"Wilson's disease (WD) is a member of a family of genetic disorders characterised by deranged copper metabolism. Inheritance is autosomal recessive, and mutations lead to dysfunction of a key Copper-transporting protein, the p-type ATPase ATP-7B. The consequence is accumulation of copper in susceptible tissues, particularly the liver and the basal ganglia of the brain, which may in turn give rise to symptomatic hepatic and/or neuropsychiatric disease. Patients with liver disease tend to present in the first two decades of life, whereas those with primarily neurologic manifestations tend to present later. Presentation with fulminant liver failure due to hepatic decompensation may require liver transplantation. Haemolytic disease is a rare presenting complaint. Although laboratory investigations have traditionally centred on measurement of free and total copper and caeruloplasmin in serum, and copper levels in urine both with and without penicillamine challenge, recent reports demonstrate that there may be a role for genotyping studies in diagnosis and characterization of WD. Radiocopper uptake studies have fallen out of favour, but a new approach using stable isotopes shows promise. Treatment is focused upon limiting copper accumulation, using Penicillamine. Zinc Acetate or Trientine offer alternatives if Penicillamine is not tolerated. Despite the fact that untreated WD is inevitably fatal, prognosis is generally good once the diagnosis is made, and it is this that mandates a high index of clinical suspicion in cases when there is unexplained liver or neurological disease in children, or in adults below 45 years of age.",Caeruloplasmin;Copper;Penicillamine;Wilson's disease;autosomal recessive inheritance;basal ganglion;ceruloplasmin blood level;chemical analysis;clinical feature;clinical trial;copper blood level;copper metabolism;drug structure;gene mutation;genetic disorder;genotype;hemolytic anemia;histopathology;human;isotope labeling;liver disease;liver failure/co [Complication];liver failure/dt [Drug Therapy];liver failure/su [Surgery];liver transplantation;molecular genetics;neuropsychiatry;prognosis;review;teratogenicity;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];acetylcysteine/dt [Drug Therapy];acetylcysteine/pd [Pharmacology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];penicillamine/ct [Clinical Trial];penicillamine/an [Drug Analysis];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];stable isotope;tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ct [Clinical Trial];trientine/an [Drug Analysis];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];Wilson disease protein/ec [Endogenous Compound];zinc acetate/ct [Clinical Trial];zinc acetate/dt [Drug Therapy];zinc acetate/to [Drug Toxicity],"Chaloner, C.",2006,,,0,0,
2122,Physiological and medicinal zinc,,anemia/si [Side Effect];anorexia nervosa/et [Etiology];antioxidant activity;article;clinical feature;clinical trial;common cold/dt [Drug Therapy];copper deficiency/si [Side Effect];diabetes mellitus;dietary intake;DNA synthesis;drug antagonism;dyslipidemia/si [Side Effect];enzyme activity;herpes simplex/dt [Drug Therapy];hormone metabolism;human;immune response;immune system;leg ulcer/dt [Drug Therapy];malabsorption;male infertility/et [Etiology];meat;neurotoxicity/si [Side Effect];neutropenia/si [Side Effect];pharmaceutical care;pharmacist;pharmacy;protein synthesis;regulatory mechanism;retina macula age related degeneration/dt [Drug Therapy];retinol deficiency/dt [Drug Therapy];risk factor;shellfish;skin disease/dt [Drug Therapy];tissue distribution;total parenteral nutrition;vegetarian diet;vision;vitamin supplementation;Wilson disease/dt [Drug Therapy];wound healing/dt [Drug Therapy];zinc blood level;zinc deficiency/di [Diagnosis];zinc deficiency/dt [Drug Therapy];zinc deficiency/et [Etiology];alpha tocopherol/ec [Endogenous Compound];calamine/cb [Drug Combination];calamine/dt [Drug Therapy];calcium/it [Drug Interaction];coal tar/cb [Drug Combination];coal tar/dt [Drug Therapy];copper/it [Drug Interaction];dipeptidyl carboxypeptidase inhibitor/it [Drug Interaction];diuretic agent/it [Drug Interaction];folic acid/it [Drug Interaction];free radical/ec [Endogenous Compound];gluconate zinc;iron/it [Drug Interaction];metallothionein/ec [Endogenous Compound];nonsteroid antiinflammatory agent/it [Drug Interaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];quinolone/it [Drug Interaction];retinol/dt [Drug Therapy];retinol binding protein/ec [Endogenous Compound];sex hormone/ec [Endogenous Compound];tetracycline/it [Drug Interaction];thiazide diuretic agent/it [Drug Interaction];trace element/do [Drug Dose];trace element/it [Drug Interaction];trace element/dt [Drug Therapy];trace element/to [Drug Toxicity];trace element/ec [Endogenous Compound];trace element/po [Oral Drug Administration];trace element/pd [Pharmacology];trace element/tp [Topical Drug Administration];zinc/ct [Clinical Trial];zinc/do [Drug Dose];zinc/it [Drug Interaction];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity];zinc/ec [Endogenous Compound];zinc/po [Oral Drug Administration];zinc/pd [Pharmacology];zinc/tp [Topical Drug Administration];zinc acetate/cm [Drug Comparison];zinc acetate/dt [Drug Therapy];zinc oxide/dt [Drug Therapy];zinc oxide/pd [Pharmacology];zinc oxide/tp [Topical Drug Administration];zinc sulfate/ct [Clinical Trial];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration],"Mason, P.",2006,04 Mar,,0,0,
2123,Extensive gray & white matter abnormalities in Wilson's disease: A case report,,ct;mri;White matter abnormalities;Wilson's disease;adolescent;anamnesis;article;bone examination;brain disease;case report;clinical feature;disease association;disease severity;gray matter;Gray scale echography;human;image analysis;laboratory test;male;neuroimaging;nuclear magnetic resonance imaging;osteopenia;osteoporosis;physical examination;white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];anticonvulsive agent/cb [Drug Combination];anticonvulsive agent/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy],"Grover, S. B.;Gupta, P.;Kumar, A.;Mahajan, H.",2006,February,,0,0,
2124,Wilson's hepatitis: Unusual presentation and survival [1],,chelation therapy;chronic liver disease;clinical feature;conservative treatment;drowsiness;flapping tremor;headache;hospital admission;human;jaundice;letter;neurologic disease;seizure/dt [Drug Therapy];therapy effect;treatment outcome;treatment response;vomiting;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];topiramate/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Dixit, V. K.;Vashistha, P.;Kate, M. P.;Abhilash, V. B.;Mohapatra, A.;Jain, A. K.",2006,01 Nov,,0,0,
2125,Acute lymphoblastic leukemia and Wilson's disease - Neurotoxicity of cytarabine. [German],"A 35-year old patient with a pre-existing diagnosis of liver cirrhosis was admitted to our hospital because of acute lymphoblastic leukemia. Neurological disturbances such as tremor and ataxia led to a diagnosis of Wilson's disease. Therapy with D-penicillamine failed to improve symptoms of CNS involvement. Polychemotherapy was tolerated without worsening of liver function and was successful with a complete remission lasting for five months. High-dose cytarabine, given for relapse, resulted in a detoriation of neurological symptoms preventing the application of aggressive chemotherapy in the subsequent course. © 2006 Schattauer GmbH.",Acute lymphoblastic leukemia;Cytarobine;Wilson's disease;acute lymphocytic leukemia/di [Diagnosis];acute lymphocytic leukemia/dt [Drug Therapy];adult;anamnesis;article;blood examination;case report;clinical feature;combination chemotherapy;dose response;hospital admission;human;laboratory diagnosis;liver cirrhosis;liver function;neurologic disease/si [Side Effect];neurotoxicity/si [Side Effect];Wilson disease/di [Diagnosis];cyclophosphamide/dt [Drug Therapy];cyclophosphamide/iv [Intravenous Drug Administration];cytarabine/ae [Adverse Drug Reaction];cytarabine/do [Drug Dose];cytarabine/dt [Drug Therapy];cytarabine/iv [Intravenous Drug Administration];cytarabine/pd [Pharmacology];daunorubicin/dt [Drug Therapy];mercaptopurine/dt [Drug Therapy];methotrexate/dt [Drug Therapy];methotrexate/po [Oral Drug Administration];mitoxantrone/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];prednisone/dt [Drug Therapy];prednisone/po [Oral Drug Administration];propranolol/dt [Drug Therapy];vincristine/dt [Drug Therapy],"Noppeney, R.;Duhrsen, U.",2006,October,,0,0,
2126,Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunction,"Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic: individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [<sup>18</sup>F]fluoro-2-deoxy-D-glucose positron emission tomography ([<sup>18</sup>F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the ""Sniffin' Sticks,"" which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit. © 2006 Movement Disorder Society.",Olfaction;Wilson's disease;adult;aged;article;basal ganglion;clinical article;clinical protocol;controlled study;degeneration;disease association;disease severity;extrapyramidal symptom;female;human;liver disease;male;nuclear magnetic resonance imaging;odor;olfactory discrimination;olfactory system;positron emission tomography;priority journal;scoring system;smelling disorder/et [Etiology];Wilson disease/dt [Drug Therapy];copper;fluorodeoxyglucose f 18;liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Muelle, A.;Reuner, U.;Landis, B.;Kitzler, H.;Reichmann, H.;Hummel, T.",2006,September,http://dx.doi.org/10.1002/mds.20989,0,0,
2127,Clinical and genetic profile in Wilson's disease: A case report with a family pedigree. [German],"Wilson's disease is a rare autosomal recessively inherited disorder of copper metabolism resulting in accumulation of copper in many organs. The Kayser-Fleischer corneal ring represents a typical symptom in Wilson patients. ATP7B, the gene product of the Wilson's disease gene, is expressed in hepatocytes and plays a critical role in copper transport and secretion. Mutations encompassing this gene leading to amino acid substitutions reduce the affinity of the ATPase enzyme to copper and prevent the transport of copper through the hepatocytes into the bile duct. More than 200 mutations in the 21 coding exons of the Wilson's disease gene ATP7B have been described, the most common European one being His1069Gln (30-60% in European patients). Wilson's disease may present with various clinical symptoms, commonly as liver and neuropsychiatric disease. The diagnosis of Wilson's disease (prevalence 1:30000) is based on a combination of clinical and neurological symptoms (Kayser-Fleischer corneal ring, MRI), a multi-parametric clinical chemistry panel (ceruloplasmin, 24 h-copper excretion in urine, serum copper) and molecular genetic analysis of ATP7B gene mutations. Symptomatic patients are treated with the chelating agents D-penicillamine or trientine, and in a second phase often with zinc. Lifelong therapy is required and provides life expectancy near to normal. Here, we report on the long-term follow-up of a 30-year-old Wilson patient displaying a compound heterozygosity of His1069Gln - Asn1270Ser mutations in the ATP7B gene as diagnosed by LightCycler real time polymerase chain reaction and DNA sequencing of exon 18. Molecular family-pedigree analysis over four generations revealed seven additional heterozygous mutation carriers. Treatment of the index patient with high doses of chelating agent D-penicillamine (1500 mg/d) in combination with zinc (150 mg/d) could reverse copper encephalopathy to normal and markedly reduced neurological symptoms. Kayser-Fleischer corneal ring was persistent. Wilson's disease should be taken into consideration in case of any liver disease of unknown origin or neuropsychiatric symptoms. Current diagnostic panels (international scoring system) encompassing clinical chemistry and molecular genetics for screening and confirmation of Wilson's disease are discussed.",atp7b;Copper;D-penicillamine;Wilson's disease;adult;article;ATP7B gene;autosomal recessive disorder;case report;clinical feature;gene;gene expression;gene mutation;human;life expectancy;long term care;polymerase chain reaction;prevalence;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Noppen, C.;Aerne-Wyrsch, L.;Wyrschs, J.;Viollier, E. H.;Hess, K.;Schaefer, C.",2006,October,,0,0,
2128,Copper kinetics and hepatic glutathione levels in the copper exposed frog Rana ridibunda after tetrathiomolybdate treatment,,animal cell;animal experiment;animal model;animal tissue;aqueous solution;article;chelation;concentration response;controlled study;copper metabolism;female;frog;glutathione metabolism;nonhuman;Wilson disease/et [Etiology];copper/to [Drug Toxicity];glutathione/ec [Endogenous Compound];tetrathiomolybdic acid/pd [Pharmacology],"Loumbourdis, N. S.",2006,March,http://dx.doi.org/10.1007/s00128-006-0951-9,0,0,
2129,Wilson's disease: A patient undiagnosed for 18 years,"Wilson's disease, an autosomal recessive disorder of copper metabolism, is the most common inherited hepatic disease in Hong Kong. Diagnosis is based on the presence of Kayser-Fleischer rings, typical neurological symptoms, and/or a low serum ceruloplasmin concentration (<0.20 g/L). Early detection and treatment protect patients and their presymptomatic siblings from devastating organ damage. The diagnosis of Wilson's disease may nonetheless be overlooked if only established clinical and laboratory tests are used as diagnostic criteria. We report diagnosis of the disorder using genetic analysis of ATP7B in a presymptomatic sibling who escaped diagnosis during family screening 18 years previously. The patient was 11 months old when family screening was performed following diagnosis of Wilson's disease in an elder sister. The boy was considered to be unaffected on the basis of laboratory results in the expected range: serum copper level, 4.6 mumol/L; serum ceruloplasmin level, 0.16 g/L; and 24-hour urinary copper excretion, 0.14 mumol/day. Molecular analysis of ATP7B was performed; it revealed that the two siblings shared the same compound heterozygous mutations (G943D and 2299delC). We recommend that molecular diagnosis is the only definitive means of diagnosing Wilson's disease in children younger than 1 year.",Adenosinetriphosphatase/genetics;Ceruloplasmin;Copper/metabolism;Hepatolenticular degeneration;Liver diseases;adult;article;case report;ceruloplasmin blood level;clinical examination;codon;copper blood level;drug tolerance;female;gene mutation;genetic analysis;heterozygosity;heterozygote detection;human;laboratory test;male;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Mak, C. M.;Tam, S.;Fan, S. T.;Liu, C. L.;Lam, C. W.",2006,April,,0,0,
2130,A novel mutation in ATP7B gene associated with severe neurological and psychiatric symptoms [3],,adult;ataxia/dt [Drug Therapy];brain atrophy;case report;female;gene mutation;human;letter;mental disease;neurologic disease;non insulin dependent diabetes mellitus;priority journal;tremor/dt [Drug Therapy];Wilson disease;penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Mihaylova, V.;Todorov, T.;Tournev, I.;Cherninkova, S.;Nikoevski, N.;Raicheva, M.;Iankova, P.;Petrova, I.;Savov, A.;Kremesky, I.",2006,May,http://dx.doi.org/10.1159/000092783,0,0,
2131,CNS demyelination due to hypocupremia in Wilson's disease from overzealous treatment,,adolescent;article;brain atrophy;case report;central nervous system;clinical feature;computer assisted tomography;copper deficiency/si [Side Effect];demyelination/et [Etiology];frontal cortex;human;male;parietal lobe;symptomatology;temporal cortex;white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Narayan, S. K.;Kaveer, N.",2006,01 Jan,,0,0,
2132,Painless legs moving toes in a patient with Wilson's disease,"We describe and present a video of a 20-year-old woman with Wilson's disease (WD) who developed the painless variant of painful legs and moving toes (PLMT) syndrome. The symptoms appeared during a subsequent minor exacerbation of her extrapyramidal symptomatology, only to gradually disappear 3 to 4 months later. We suggest that, in our case, a structural central nervous system lesion caused by WD may have been associated with the development of PLMT. © 2006 Movement Disorder Society.",Etiology;Moving toes;Painful legs;Painless legs;Wilson's disease;adult;article;bradykinesia;case report;central nervous system disease;clinical feature;disease association;disease course;disease duration;disease exacerbation;dose response;extrapyramidal symptom/dt [Drug Therapy];female;human;involuntary movement;laboratory test;mental disease/dt [Drug Therapy];motor dysfunction/dt [Drug Therapy];motor performance;nausea/si [Side Effect];neurologic examination;nuclear magnetic resonance imaging;priority journal;rest;speech disorder;toe;tremor;videorecording;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];paroxetine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trihexyphenidyl/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];zinc acetate/cb [Drug Combination];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy],"Papapetripoulos, S.;Singer, C.",2006,April,http://dx.doi.org/10.1002/mds.20805,0,0,
2133,Wilson's disease: Cranial MRI observations and clinical correlation,"Introduction: Study of MRI changes may be useful in diagnosis, prognosis and better understanding of the pathophysiology of Wilson's disease (WD). We aimed to describe and correlate the MRI abnormalities of the brain with clinical features in WD. Methods: MRI evaluation was carried out in 100 patients (57 males, 43 females; mean age 19.3+/-8.9 years) using standard protocols. All but 18 patients were on de-coppering agents. Their history, clinical manifestations and scores for severity of disease were noted. Results: The mean duration of illness and treatment were 8.3+/-10.8 years and 7.5+/-7.1 years respectively. MRI of the brain was abnormal in all the 93 symptomatic patients. The most conspicuous observations were atrophy of the cerebrum (70%), brainstem (66%) and cerebellum (52%). Signal abnormalities were also noted: putamen (72%), caudate (61%), thalami (58%), midbrain (49%), pons (20%), cerebral white matter (25%), cortex (9%), medulla (12%) and cerebellum (10%). The characteristic T2-W globus pallidal hypointensity (34%), ""Face of giant panda"" sign (12%), T1-W striatal hyperintensity (6%), central pontine myelinosis (7%), and bright claustral sign (4%) were also detected. MRI changes correlated with disease severity scores (P<0.001) but did not correlate with the duration of illness. Conclusion: MRI changes were universal but diverse and involved almost all the structures of the brain in symptomatic patients. A fair correlation between MRI observations and various clinical features provides an explanation for the protean manifestations of the disease. © Springer-Verlag 2006.",mri;Wilson's disease;adolescent;adult;article;brain atrophy;brain cortex;brain stem;caudate nucleus;cerebellum atrophy;chelation therapy;child;clinical feature;controlled study;correlation analysis;disease duration;disease severity;female;globus pallidus;human;major clinical study;male;medulla oblongata;mesencephalon;nuclear magnetic resonance imaging;pons;priority journal;putamen;statistical significance;thalamus;treatment duration;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Sinha, S.;Taly, A. B.;Ravishankar, S.;Prashanth, L. K.;Venugopal, K. S.;Arunodaya, G. R.;Vasudev, M. K.;Swamy, H. S.",2006,September,http://dx.doi.org/10.1007/s00234-006-0101-4,0,1,
2134,Copper deficiency and its hematologic manifestations,,anemia;bariatric surgery;clinical feature;copper blood level;copper deficiency/co [Complication];copper deficiency/dt [Drug Therapy];copper deficiency/et [Etiology];copper deficiency/si [Side Effect];gastrointestinal surgery;hematologic disease/dt [Drug Therapy];hematologic disease/si [Side Effect];heme synthesis;human;infant;myelodysplastic syndrome;neurologic disease;neutropenia;note;pancytopenia;postoperative complication/co [Complication];prematurity;short bowel syndrome;total parenteral nutrition;Wilson disease;ceruloplasmin/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/ec [Endogenous Compound];cytochrome c oxidase/ec [Endogenous Compound];ferric ion/ec [Endogenous Compound];ferrous ion/ec [Endogenous Compound];heme/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];transferrin/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/to [Drug Toxicity],"Phyliky, R. L.",2006,February,,0,0,
2135,Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period,"This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg<sup>-1</sup> day<sup>-1</sup> and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg<sup>-1</sup> day<sup>-1</sup> DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period. Copyright © 2005 John Wiley & Sons, Ltd.",Copper depletion;D-penicillamine;Desmosine;Elastin;Isodesmosine;Perinatal period;animal experiment;animal model;animal tissue;article;atomic absorption spectrometry;body weight;controlled study;copper blood level;cross linking;cystinuria;drug contraindication;drug effect;drug mechanism;drug safety;elasticity;elastin cross linking;elastin metabolism;female;fetotoxicity;fetus lung maturation;high performance liquid chromatography;lung parenchyma;lung weight;newborn;nonhuman;pregnancy;priority journal;protein metabolism;rat;rheumatoid arthritis;Wilson disease;ceruloplasmin/ec [Endogenous Compound];chelating agent;desmosine/ec [Endogenous Compound];elastin/ec [Endogenous Compound];isodesmosine/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/to [Drug Toxicity];penicillamine/ip [Intraperitoneal Drug Administration];penicillamine/pd [Pharmacology],"Kocturk, S.;Oktay, G.;Guner, G.;Pekcetin, C.;Gure, A.",2006,March/April,http://dx.doi.org/10.1002/cbf.1209,0,0,
2136,First reports of adverse drug reactions in recent weeks,,abdominal cramp;acute granulocytic leukemia/si [Side Effect];adrenal insufficiency/si [Side Effect];alopecia/si [Side Effect];anuria/si [Side Effect];autism/dt [Drug Therapy];blepharospasm/si [Side Effect];bradycardia/dt [Drug Therapy];bradycardia/si [Side Effect];brain disease;brain injury;Capnocytophaga;cellulitis/si [Side Effect];cholestatic hepatitis/si [Side Effect];coma/si [Side Effect];contact dermatitis/si [Side Effect];dexamethasone suppression test;diagnostic error;disease exacerbation/si [Side Effect];drug eruption/si [Side Effect];drug formulation;drug hypersensitivity/si [Side Effect];drug overdose;eyelid edema/si [Side Effect];facial nerve disease/si [Side Effect];food drug interaction;gastrointestinal hemorrhage/si [Side Effect];heart arrest/si [Side Effect];hemolysis/si [Side Effect];hepatitis B/dt [Drug Therapy];human;Human immunodeficiency virus infection/dt [Drug Therapy];hypoglycemia/si [Side Effect];hyponatremia/si [Side Effect];immunoglobulin deficiency/si [Side Effect];infectious arthritis/si [Side Effect];insulin dependent diabetes mellitus/dt [Drug Therapy];kidney tubule disorder/si [Side Effect];liver failure/si [Side Effect];liver fibrosis/si [Side Effect];major depression/dt [Drug Therapy];melena/si [Side Effect];mixed connective tissue disease/dt [Drug Therapy];motor neuropathy/si [Side Effect];myasthenia gravis;nausea and vomiting/si [Side Effect];nephrotoxicity/si [Side Effect];nerve block;nerve injury/si [Side Effect];neuroleptic malignant syndrome/si [Side Effect];obsessive compulsive disorder/si [Side Effect];obstructive jaundice/si [Side Effect];occlusive cerebrovascular disease/si [Side Effect];osteosclerosis/si [Side Effect];pancreas cancer/dt [Drug Therapy];panniculitis/si [Side Effect];paresthesia/si [Side Effect];phlebitis/si [Side Effect];polychondritis/si [Side Effect];polyradiculoneuropathy/si [Side Effect];pseudogout/si [Side Effect];pustulosis/si [Side Effect];review;rhabdomyolysis/si [Side Effect];rheumatoid arthritis/dt [Drug Therapy];rheumatoid nodule/si [Side Effect];side effect/si [Side Effect];skin atrophy/si [Side Effect];sleep walking/si [Side Effect];somatoform disorder/si [Side Effect];spinal cord injury/dt [Drug Therapy];thrombocytopenia/si [Side Effect];thrombosis/si [Side Effect];thrombotic thrombocytopenic purpura/si [Side Effect];tonic clonic seizure/si [Side Effect];toxic epidermal necrolysis/si [Side Effect];urticaria/si [Side Effect];uveitis/si [Side Effect];Wilson disease/dt [Drug Therapy];abacavir/ae [Adverse Drug Reaction];abacavir/dt [Drug Therapy];alendronic acid/ae [Adverse Drug Reaction];amisulpride/ae [Adverse Drug Reaction];amprenavir/ae [Adverse Drug Reaction];amprenavir/dt [Drug Therapy];antiretrovirus agent/ae [Adverse Drug Reaction];atorvastatin/ae [Adverse Drug Reaction];atorvastatin/it [Drug Interaction];basiliximab/ae [Adverse Drug Reaction];bicarbonate/dt [Drug Therapy];bicarbonate/iv [Intravenous Drug Administration];bromazepam/to [Drug Toxicity];cancer vaccine/ae [Adverse Drug Reaction];cancer vaccine/dt [Drug Therapy];carbamazepine/ae [Adverse Drug Reaction];carbamazepine/dt [Drug Therapy];carcinoembryonic antigen/ec [Endogenous Compound];chloroquine/ae [Adverse Drug Reaction];chloroquine/dt [Drug Therapy];cisplatin/ae [Adverse Drug Reaction];citalopram/to [Drug Toxicity];cyclosporin A/ae [Adverse Drug Reaction];cytotoxic T lymphocyte antigen 4/ec [Endogenous Compound];dexamethasone/ae [Adverse Drug Reaction];dexamethasone/it [Drug Interaction];dexamethasone/dt [Drug Therapy];doxorubicin/ae [Adverse Drug Reaction];drug/ae [Adverse Drug Reaction];escitalopram/ae [Adverse Drug Reaction];etanercept/ae [Adverse Drug Reaction];etanercept/dt [Drug Therapy];etoposide/ae [Adverse Drug Reaction];fluoxetine/ae [Adverse Drug Reaction];flupirtine/to [Drug Toxicity];gadodiamide/ae [Adverse Drug Reaction];imatinib/ae [Adverse Drug Reaction];immunosuppressive agent/ae [Adverse Drug Reaction];infliximab/ae [Adverse Drug Reaction];infliximab/dt [Drug Therapy];influenza vaccine/ae [Adverse Drug Reaction];influenza vaccine/pr [Pharmaceutics];insulin glargine/ae [Adverse Drug Reaction];insulin glargine/dt [Drug Therapy];iodine 131/ae [Adverse Drug Reaction];isotretinoin/ae [Adverse Drug Reaction];lamivudine/ae [Adverse Drug Reaction];lamivudine/dt [Drug Therapy];levobupivacaine/ae [Adverse Drug Reaction];levobupivacaine/ei [Epidural Drug Administration];lindane/ae [Adverse Drug Reaction];lindane/tp [Topical Drug Administration];mannan/ae [Adverse Drug Reaction];methadone/ae [Adverse Drug Reaction];methylprednisolone/ae [Adverse Drug Reaction];methylprednisolone/dt [Drug Therapy];methylprednisolone acetate/ae [Adverse Drug Reaction];monoclonal antibody/ae [Adverse Drug Reaction];moxifloxacin/ae [Adverse Drug Reaction];mycophenolic acid 2 morpholinoethyl ester/ae [Adverse Drug Reaction];mycophenolic acid 2 morpholinoethyl ester/to [Drug Toxicity];nevirapine/ae [Adverse Drug Reaction];nevirapine/dt [Drug Therapy];olanzapine/ae [Adverse Drug Reaction];oxaliplatin/ae [Adverse Drug Reaction];piperacillin plus tazobactam/ae [Adverse Drug Reaction];potassium chloride/ae [Adverse Drug Reaction];prednisolone/ae [Adverse Drug Reaction];prednisone/ae [Adverse Drug Reaction];reboxetine/ae [Adverse Drug Reaction];reboxetine/dt [Drug Therapy];recombinant blood clotting factor 7a/ae [Adverse Drug Reaction];rivastigmine/ae [Adverse Drug Reaction];rosuvastatin/ae [Adverse Drug Reaction];simvastatin/ae [Adverse Drug Reaction];st 157;tacrolimus/ae [Adverse Drug Reaction];tadalafil/ae [Adverse Drug Reaction];thiomersal;thymocyte antibody/ae [Adverse Drug Reaction];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];unclassified drug;vardenafil/ae [Adverse Drug Reaction];zidovudine/ae [Adverse Drug Reaction];zidovudine/dt [Drug Therapy];zonisamide/ae [Adverse Drug Reaction];zopiclone/to [Drug Toxicity],Anonymous,2005,May,http://dx.doi.org/10.2165/00042310-200521050-00006,0,0,
2137,Importance of molecular genetic examination for diagnostics of Wilson disease. [Czech],"Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) transport with a frequency of 1:40,000 live birth. The disease is caused by a deficiency of copper-transporting ATPase - ATP7B (13q14.3-q21.1). The disorder becomes manifest as a chronic liver disease and/or neurological impairment due to accumulation of copper in several tissues, principally the liver and brain. The most frequent manifestation of WD is between 8 and 20 years of age. The diagnosis involves determination of serum ceruloplasmine and Cu, detection of Cu in 24-hour collection of urine, carrying out a test with penicillamine, liver biopsy determining the Cu content in the hepatic dry weight and DNA diagnosis, if available. Interpretation of biochemical findings changes due to DNA analysis of mutations. As yet there is no exact correlation between the genotype and phenotype of the patient. Therapy of the disease is developing and at the present time is accepted for the hepatic from in childhood as a standard therapy with chelates and zinc. In the final stage the solution would be liver transplantation. The group included 22 children from 5 to 17 years of age. The 1<sup>st</sup> group (12) consisted of heterozygotes for WD, siblings or offspring of patients with WD confirmed by DNA diagnosis. The 2<sup>nd</sup> group (10) were patients with hepatic form of WD, confirmed by DNA diagnosis and assessment of the copper content in hepatic dry weight. The control group consisted of 11 children aged 4 to 16 years. In 4 probands of the 1st group, i.e. 33.3%, authors discovered that the level of ceruloplasmine in blood had decreased below 0.2 g/l (ranging between 0.12 and 0.43 g/l). They proved a statistically significant difference (P < 0.05) for CP in the serum among heterozygotes for WD; i.e. among the offspring of mothers with WD and siblings of probands with WD. Threshold levels of copper were determined in the basic collection of urine of 4 children (i.e. 0.6 mumol). The copper level in the 24-hour urine collection of 11 heterozygotes in the test with penicillamine did not exceed 12.5 mumol. In 7 children of the 2<sup>nd</sup> group authors demonstrated a serum level of ceruloplasmine lower than 0.2 g/l, i.e. 70% (between 0.03 and 0.22 g/l). All the 24-hour urine collections for copper contained elevated residues of more than 0.6 mumol (between 0.8 and 2.67 mumol). Contrary to expectations levels higher than 1.6 mumol were detected only in 4 children. A statistically significant difference (P < 0.05) in the 24-hour excretion of copper into urine was discovered between the control group of healthy children and probands with WD, also according to the sex of the investigated individuals. In the test with penicillamine the Cu residue in urine was lower than 20 mumol (indicated as an extreme level for WD) in 8 probands. Urinary copper excretion after penicillamine administration do not contribute to the differentiation of heterozygotes and patients with WD. An important way of screening is the determination of the copper content in hepatic dry weight. However, authors assume that interpretation of these findings will change in the near future in view of DNA diagnosis of mutations. According to these results examinations of the Kayser-Fleischer ring in early childhood hepatic forms are not very important. In a proband with the genotype IVS12+1G>A/G1355C they discovered that the heavier the form of mutation demonstrated in a WD patient, the more severe the clinical course of the disease can be expected. Serious mutation in the heterozygotes may mimic WD. Authors recorded an attack of anxiety disorder in a girl with the genotype H1069Q/W779X. In children with the allele H1069Q they demonstrated minimal brain damage, graphomotoric inaptitude and slightly abnormal EEG in the basic activity without a clinical correlate.",Genotype;Phenotype;Wilson disease;adolescent;article;autosomal recessive disorder;brain;child;chronic liver disease;clinical article;clinical feature;correlation analysis;disease course;DNA determination;electroencephalogram;female;genetic analysis;heterozygote;human;human tissue;liver;liver biopsy;liver transplantation;liver weight;male;molecular genetics;neurologic disease;nucleotide sequence;urinalysis;Wilson disease/di [Diagnosis];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent;copper/ec [Endogenous Compound];penicillamine;Wilson disease protein/ec [Endogenous Compound];zinc,"Prochazkova, D.;Konecna, P.;Vrabelova, S.;Kozak, L.;Dastych, M.;Hrstkova, H.",2005,,,0,0,
2138,Status dystonicus: Study of five cases,"Status Dystonicus (SD) is characterized by generalized muscle contractions in dystonic patients. We report 5 cases of SD, two of which in patients with dystonic cerebral palsy, one in a patient with primary segmental dystonia, one in a patient with Hallervorden-Spatz syndrome and one in a patient with Wilson's disease (WD). Three patients were admitted to an intensive care unit and treated with propofol and midazolam, and two were submitted to neurosurgical procedures (bilateral pallidotomy and bilateral pallidal deep brain stimulation). Triggering factors were identified in three patients as follows: infection, stress-induced and zinc therapy for WD. On follow-up, two patients presented with significant improvement of dystonia, whereas the other three cases the clinical picture ultimately returned to baseline pre-SD condition.","""Status dystonicus"";Dystonia;Dystonic storm;adult;article;brain depth stimulation;cerebral palsy;ceruloplasmin blood level;clinical article;copper blood level;creatine kinase blood level;drug induced disease/si [Side Effect];dystonia/dt [Drug Therapy];dystonia/si [Side Effect];dystonia/su [Surgery];dystonia/th [Therapy];follow up;Hallervorden Spatz disease;human;infection;intensive care;male;pallidotomy;risk factor;school child;status dystonicus/dt [Drug Therapy];status dystonicus/si [Side Effect];status dystonicus/su [Surgery];status dystonicus/th [Therapy];stress;Wilson disease/dt [Drug Therapy];baclofen/cb [Drug Combination];baclofen/dt [Drug Therapy];biperiden/cb [Drug Combination];biperiden/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];carbamazepine/cb [Drug Combination];carbamazepine/dt [Drug Therapy];carbidopa plus levodopa/cb [Drug Combination];carbidopa plus levodopa/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chlorpromazine/cb [Drug Combination];chlorpromazine/dt [Drug Therapy];clobazam/cb [Drug Combination];clobazam/dt [Drug Therapy];clonazepam/cb [Drug Combination];clonazepam/dt [Drug Therapy];copper/ec [Endogenous Compound];creatine kinase/ec [Endogenous Compound];diazepam/cb [Drug Combination];diazepam/dt [Drug Therapy];flurazepam/cb [Drug Combination];flurazepam/dt [Drug Therapy];haloperidol/cb [Drug Combination];haloperidol/dt [Drug Therapy];midazolam/cb [Drug Combination];midazolam/dt [Drug Therapy];periciazine/cb [Drug Combination];periciazine/dt [Drug Therapy];pimozide/cb [Drug Combination];pimozide/dt [Drug Therapy];propofol/cb [Drug Combination];propofol/dt [Drug Therapy];tetrabenazine/cb [Drug Combination];tetrabenazine/dt [Drug Therapy];trihexyphenidyl/cb [Drug Combination];trihexyphenidyl/dt [Drug Therapy];valproic acid/cb [Drug Combination];valproic acid/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy]","Teive, H. A. G.;Munhoz, R. P.;Souza, M. M.;Antoniuk, S. A.;Santos, M. L. S. F.;Jacobsen Teixeira, M.;Reis Barbosa, E.;Carvalho, R. C.;Scaff, M.;Werneck, L. C.",2005,March,,0,0,
2139,Wilson's disease in children: 37-year experience and revised King's for liver transplantation,"Wilson's disease (WD) is a rare liver-based disorder of copper metabolism. Prognostic criteria described by our group in 1986 to predict death without transplantation have not been universally validated. The clinical features of 88 children were reviewed, retrospectively in 74 and prospectively in 14. Data from the retrospectively recruited patients that died or survived on long-term chelation were used to evaluate the validity of our old scoring system and to devise a new prognostic index, then assessed in the 14 prospectively recruited patients. Using the old scoring system, 5 children scoring >= 7, the cutoff value for death without transplantation, survived, whereas 4 scoring <= 7 died (sensitivity 87% and specificity 90%). A new index based on serum bilirubin, international normalized ratio, aspartate aminotransferase (AST), and white cell count (WCC) at presentation identified a cutoff score of 11 for death and proved to be 93% sensitive and 98% specific, with a positive predictive value of 88%. When the new index was evaluated prospectively in 14 patients, it predicted the need for transplantation in only the 4 who required it, although 1 child with a score of 11 survived on medical treatment. In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients. Copyright © 2005 by the American Association for the Study of Liver Diseases.",adolescent;article;aspartate aminotransferase blood level;bilirubin blood level;bone marrow suppression/si [Side Effect];chelation therapy;child;clinical feature;controlled study;copper metabolism;drowsiness/si [Side Effect];drug eruption/si [Side Effect];female;headache/si [Side Effect];hematuria/si [Side Effect];hemolytic anemia/si [Side Effect];human;international normalized ratio;leukocyte count;liver transplantation;major clinical study;male;mortality;musculoskeletal disease/si [Side Effect];nausea/si [Side Effect];neutropenia/si [Side Effect];prediction;priority journal;prognosis;prospective study;proteinuria/si [Side Effect];retrospective study;scoring system;sensitivity and specificity;speech disorder/si [Side Effect];survival rate;teratogenicity;validation process;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Dhawan, A.;Taylor, R. M.;Cheeseman, P.;De Silva, P.;Katsiyiannakis, L.;Mieli-Vergani, G.",2005,April,http://dx.doi.org/10.1002/lt.20352,0,0,
2140,Wilson disease with an initial manifestation of polyneuropathy,"Background: Recognition of Wilson disease (WD) is sometimes difficult because of its diverse manifestations. Peripheral neuropathy is rarely reported in the context of WD. Objective: To report an unusual patient with WD whose initial manifestation was peripheral neuropathy. Design: Case report. Setting: Neurology department in a tertiary referral center. Method: Personal observation. Result: A 17-year-old man,who was eventually diagnosed with WD, was initially seen with polyneuropathy at least 6 months prior to developing more typical symptoms of WD. Electrophysiological and pathological studies suggested a neuropathy of mixed type. Treatment for WD resulted in clinical and electrophysiological improvement. Conclusion: Wilson disease may initially appear as a treatable polyneuropathy. ©2005 American Medical Association. All rights reserved.",adolescent;article;case report;clinical feature;electrophysiology;human;male;peripheral neuropathy;polyneuropathy/dt [Drug Therapy];priority journal;pyridoxine deficiency/dt [Drug Therapy];pyridoxine deficiency/pc [Prevention];pyridoxine deficiency/si [Side Effect];sensorimotor neuropathy/dt [Drug Therapy];symptomatology;Wilson disease/dt [Drug Therapy];amitriptyline/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];pyridoxine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Jung, K. H.;Ahn, T. B.;Jeon, B. S.",2005,October,http://dx.doi.org/10.1001/archneur.62.10.1628,0,0,
2141,Wilson's disease presenting as depressive disorder [6],,anamnesis;brain atrophy/di [Diagnosis];brain stem injury/di [Diagnosis];case report;clinical feature;depression/di [Diagnosis];depression/dt [Drug Therapy];Diagnostic and Statistical Manual of Mental Disorders;female;hospital admission;human;letter;medical examination;mental health;ophthalmology;putamen;school child;Wilson disease/di [Diagnosis];fluoxetine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];thioridazine/dt [Drug Therapy];zinc,"Krishnakumar, P.;Riyaz, A.",2005,November,,0,0,
2142,Wilson disease - Keeping the bar for diagnosis raised [1],,adult;ATP7B gene;case report;echography;female;gene;gene mutation;heterozygosity;human;letter;liver biopsy;liver cirrhosis/di [Diagnosis];mental disease/et [Etiology];neurologic disease/et [Etiology];portal hypertension/di [Diagnosis];priority journal;sequence analysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;trientine/dt [Drug Therapy],"Perri, R. E.;Hahn, S. H.;Ferber, M. J.;Kamath, P. S.",2005,October,http://dx.doi.org/10.1002/hep.20893,0,0,
2143,The liver in pregnancy: Disease vs benign changes,"Liver dysfunction in a pregnant woman may be caused by the pregnancy, it may be unrelated to the pregnancy, or it may be a chronic condition that existed before the pregnancy. In any case, the clinical clues of liver dysfunction in pregnancy are not specific, and certain ""abnormalities"" in liver function tests may represent benign changes of pregnancy. On the other hand, prompt recognition of the signs of liver disease in pregnant patients leads to timely management and may save the life of both mother and baby.",alcohol abstinence;article;autoimmune hepatitis/dt [Drug Therapy];Budd Chiari syndrome/di [Diagnosis];Budd Chiari syndrome/dt [Drug Therapy];Budd Chiari syndrome/su [Surgery];chronic disease;clinical feature;cytomegalovirus infection;differential diagnosis;drug dose reduction;early diagnosis;eclampsia/co [Complication];eclampsia/dt [Drug Therapy];erythema;esophagus varices bleeding/dt [Drug Therapy];esophagus varices bleeding/su [Surgery];fatty liver/su [Surgery];female;fluid therapy;gallstone/su [Surgery];hand palm;HELLP syndrome/co [Complication];Hepatitis B virus;herpes simplex/dt [Drug Therapy];high risk pregnancy/co [Complication];human;hyperemesis gravidarum/th [Therapy];hypoalbuminemia;intrahepatic cholestasis/dt [Drug Therapy];jaundice/et [Etiology];laboratory test;liver cirrhosis;liver dysfunction/co [Complication];liver dysfunction/di [Diagnosis];liver dysfunction/dt [Drug Therapy];liver dysfunction/et [Etiology];liver function test;portal hypertension;preeclampsia/co [Complication];preeclampsia/dt [Drug Therapy];pregnancy complication/co [Complication];pregnancy complication/di [Diagnosis];pregnancy complication/et [Etiology];prenatal screening;primary biliary cirrhosis/dt [Drug Therapy];skin hemangioma;teratogenicity;treatment indication;vein ligation;vertical transmission;virus hepatitis/dt [Drug Therapy];virus hepatitis/pc [Prevention];virus transmission;Wilson disease/dt [Drug Therapy];aciclovir/dt [Drug Therapy];alkaline phosphatase/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];anticoagulant agent/dt [Drug Therapy];antihypertensive agent/dt [Drug Therapy];azathioprine/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];diuretic agent/dt [Drug Therapy];fibrinolytic agent/dt [Drug Therapy];hepatitis A vaccine/dt [Drug Therapy];hepatitis B vaccine/dt [Drug Therapy];interferon;lamivudine/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];magnesium sulfate/dt [Drug Therapy];methyldopa/dt [Drug Therapy];octreotide/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];ribavirin;trientine/do [Drug Dose];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];warfarin;zinc/dt [Drug Therapy],"Wakim-Fleming, J.;Zein, N. N.",2005,August,,0,0,
2144,Cutaneous manifestations of metabolic diseases: Uncommon presentations,"Metabolic diseases are common diseases in the Western world. Many of these diseases, including diabetes mellitus, hyperlipidproteinemia, gout, calcinosis, and hemochromatosis, are associated with skin diseases or often present with specific cutaneous signs. A knowledge of cutaneous manifestations helps to identify patients at risk, establish the internal diagnosis, and monitor the adverse effects of therapy. © 2005 Elsevier Inc. All rights reserved.",acrodermatitis enteropathica;allergy/si [Side Effect];article;bleeding;calcinosis;carbohydrate metabolism;clinical feature;copper metabolism;diabetes mellitus/dt [Drug Therapy];dialysis;erythema;fistula;gout;hair;hemochromatosis;hepatic porphyria;histology;human;Hunter syndrome;Hurler syndrome;hyperlipidemia;hyperpigmentation;iron metabolism;lipid metabolism;lipidosis;lipoatrophy/si [Side Effect];lipohypertrophy/si [Side Effect];lipoprotein metabolism;Maroteaux Lamy syndrome;Menkes syndrome;metabolic disorder;Morquio syndrome;mucinosis;mucopolysaccharidosis type 7;mucosa;nail disease;necrosis;oxalosis;papule;parathyroidectomy;photoallergy/si [Side Effect];pigment disorder;porphyria;porphyrin metabolism;priority journal;protein blood level;pruritus;risk assessment;Sanfilippo syndrome;Scheie syndrome;scleroderma;skin burning sensation;skin nodule;tumor;ulcer;Wilson disease;zinc metabolism;amino acid;antidiabetic agent/ae [Adverse Drug Reaction];antidiabetic agent/dt [Drug Therapy];antidiabetic agent/po [Oral Drug Administration];calcium;copper;glutaric acid;glycosaminoglycan;insulin/ae [Adverse Drug Reaction];insulin/dt [Drug Therapy];iron;porphyrin;zinc,"Kostler, E.;Porst, H.;Wollina, U.",2005,September/October,http://dx.doi.org/10.1016/j.clindermatol.2005.01.008,0,0,
2145,Liver transplantation for Wilson's disease: The burden of neurological and psychiatric disorders,"A retrospective data analysis on liver transplantation for Wilson's disease (WD) was performed among Italian Liver Transplant Centers. Thirty-seven cases were identified. The main indication for liver transplantation was chronic advanced liver disease in 78% of patients. Mixed hepatic and neuropsychiatric symptoms were recorded in 32.3%. Eight patients presented with fulminant liver failure; 44.8% were on medical treatment. Patient and graft survival at 3 months, 12 months, 3 years, 5 years, and 10 years after transplantation were, respectively, 91.8%, 89.1%, 82.9%, 75.6%, and 58.8%, and 85.3%, 83.0%, 77.1%, 70.3%, and 47.2%. Neurological symptoms significantly improved after orthotopic liver transplantation (OLT), but the survival of patients with mixed hepatic and neuropsychiatric involvement was significantly lower than in patients with liver disease alone (P = 0.04). WD characterized by hepatic involvement alone is a rare but good indication for liver transplantation when specific medical therapy fails. Patients with neuropsychiatric signs have a significantly shorter survival even though liver transplantation has a positive impact on neurological symptoms. In conclusion, a combination of hepatic and neuropsychiatric conditions deserves careful neurological evaluation, which should contraindicate OLT in case of severe neurological impairment. Copyright © 2005 by the American Association for the Study of Liver Diseases.",adult;article;chronic liver disease/dt [Drug Therapy];chronic liver disease/su [Surgery];clinical article;controlled study;data analysis;disease severity;female;graft survival;health care facility;human;Italy;liver failure;liver graft rejection/co [Complication];liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver transplantation;male;medical documentation;mental disease;neurologic disease;priority journal;retrospective study;statistical significance;survival rate;survival time;symptomatology;treatment failure;treatment indication;Wilson disease/su [Surgery];antivirus agent;cyclosporin A/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];steroid/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Medici, V.;Mirante, V. G.;Fassati, L. R.;Pompili, M.;Forti, D.;Del Gaudio, M.;Trevisan, C. P.;Cillo, U.;Sturniolo, G. C.;Fagiuoli, S.;Andriulli, A.;Angelico, M.;Aresu, G.;Burra, P.;Caccamo, L.;Castagneto, M.;D'Amico, D. F.;Dardano, G.;Filla, A.;Gasbarrini, A.;Gasbarrini, G.;Gianni, S.;Grazi, G. L.;Martines, D.;Marzano, A.;Melada, E.;Nardo, B.;Pevere, S.;Rapaccini, G. L.;Rizzetto, M.;Rondinara, G. F.;Salizzoni, M.;Slim, A. O.;Strazzabosco, M.;Tisone, G.;Valente, U.;Zanus, G.",2005,September,http://dx.doi.org/10.1002/lt.20486,0,0,
2146,Erythematous plaques on the flexural surfaces,,acanthosis/di [Diagnosis];acanthosis/dt [Drug Therapy];acanthosis/th [Therapy];adult;anamnesis;article;carbon dioxide laser;case report;clinical feature;drug withdrawal;elastosis/dt [Drug Therapy];elastosis/si [Side Effect];elastosis/th [Therapy];elastosis perforans serpiginosa/dt [Drug Therapy];elastosis perforans serpiginosa/si [Side Effect];elastosis perforans serpiginosa/th [Therapy];endometriosis/dt [Drug Therapy];erythema/dt [Drug Therapy];erythema/th [Therapy];female;human;laboratory test;low level laser therapy;priority journal;pulsed dye laser;Wilson disease/dt [Drug Therapy];isotretinoin/dt [Drug Therapy];liquid nitrogen/dt [Drug Therapy];medroxyprogesterone acetate/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];triamcinolone/dt [Drug Therapy];triamcinolone/il [Intralesional Drug Administration];zinc acetate/dt [Drug Therapy],"Davis, D. M. R.;Otley, C. C.;Witman, P. M.",2005,November,,0,0,
2147,Extrapyramidal and cerebellar movement disorder in association with heterozygous ceruloplasmin gene mutation [6],,aceruloplasminemia/dt [Drug Therapy];adolescent;ataxia;case report;cerebellum disease;degenerative disease/dt [Drug Therapy];dementia;diagnostic procedure;extrapyramidal syndrome;female;gene mutation;human;hyperkinesia;laboratory test;letter;liver biopsy;motor dysfunction;physical examination;priority journal;retina degeneration;Wilson disease;ceruloplasmin/ec [Endogenous Compound];deferoxamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Kuhn, J.;Miyajima, H.;Takahashi, Y.;Kunath, B.;Hartmann-Klosterkoetter, U.;Cooper-Mahkorn, D.;Schaefer, M.;Bewermeyer, H.",2005,January,http://dx.doi.org/10.1007/s00415-005-0608-3,0,0,
2148,Role of animal models in the study of drug-induced hypersensitivity reactions,"Drug-induced hypersensitivity reactions (DHRs) are a major problem, in large part because of their unpredictable nature. If we understood the mechanisms of these reactions better, they might be predictable. Their unpredictable nature also makes mechanistic studies very difficult, especially prospective clinical studies. Animal models are vital to most biomedical research, and they are almost the only way to test basic hypotheses of DHRs, such as the involvement of reactive metabolites. However, useful animal models of DHRs are rare because DHRs are also unpredictable in animals. For example. sulfonamide-induced DHRs in large-breed dogs appear to be valid because they are very similar to the DHRs that occur in humans, however. the incidence is only ~0.25%, and large-breed dogs are difficult to use as an animal model. Two more practical models are penicillamine-induced autoimmunity in the Brown Norway rat and nevirapine-induced skin rash in rats, The toxicity in these models is clearly immune mediated. In other models, such as amodiaquine-induced agranulocytosis/hepatotoxicity and halothane-induced hepatotoxicity, the drug induces an immune response but there is no clinical toxicity. This finding suggests that regulatory mechanisms usually limit toxicity. Many of the basic characteristics of the penicillamine and nevirapine models, such as memory and tolerance, are quite different suggesting that the mechanisms are also significantly different. More animal models are needed to study the range of mechanisms involved in DHRs; without them, progress in understanding such reactions is likely to be slow. Copyright ©2003. All Rights Reserved.",Animal models;Hypersensitivity reactions;Idiosyncratic drug reactions;Nevirapine;Penicillamine;Popliteal lymph node assay;agranulocytosis/si [Side Effect];amnesia;animal disease;animal model;arthritis;arthropathy/si [Side Effect];autoimmunity;body weight disorder/si [Side Effect];breeding;cat disease;clinical study;Coombs positive hemolytic anemia;dog disease;drug eruption/si [Side Effect];drug hypersensitivity/si [Side Effect];experimental model;fever/si [Side Effect];guinea pig;hemolytic anemia/si [Side Effect];human;Human immunodeficiency virus infection/dt [Drug Therapy];Human immunodeficiency virus infection/pc [Prevention];hyperthyroidism/dt [Drug Therapy];hypoxia;immune response;immunological tolerance;immunotoxicity;incidence;keratoconjunctivitis sicca/si [Side Effect];lethargy;leukopenia/si [Side Effect];liver injury/si [Side Effect];liver necrosis;liver toxicity/si [Side Effect];lupus like syndrome/si [Side Effect];lymph node;medical research;metabolite;mouse;myasthenia gravis/si [Side Effect];neutropenia/si [Side Effect];nonhuman;pemphigus/si [Side Effect];prospective study;protein synthesis inhibition;rat;review;rheumatoid arthritis/dt [Drug Therapy];screening test;thrombocytopenia/si [Side Effect];toxic epidermal necrolysis;Wilson disease/dt [Drug Therapy];1 aminobenzotriazole/cb [Drug Combination];1 aminobenzotriazole/to [Drug Toxicity];aminoguanidine/pd [Pharmacology];amodiaquine/ae [Adverse Drug Reaction];amodiaquine/to [Drug Toxicity];antimalarial agent/ae [Adverse Drug Reaction];antimalarial agent/to [Drug Toxicity];cyclosporin/cb [Drug Combination];cyclosporin/dt [Drug Therapy];cyclosporin/pd [Pharmacology];cytochrome P450/ec [Endogenous Compound];halothane/ae [Adverse Drug Reaction];halothane/to [Drug Toxicity];immunosuppressive agent/cb [Drug Combination];immunosuppressive agent/dt [Drug Therapy];immunosuppressive agent/pd [Pharmacology];isoniazid/ae [Adverse Drug Reaction];isoniazid/to [Drug Toxicity];lipopolysaccharide/to [Drug Toxicity];methyldopa/to [Drug Toxicity];misoprostol/pd [Pharmacology];nevirapine/ae [Adverse Drug Reaction];nevirapine/cb [Drug Combination];nevirapine/cm [Drug Comparison];nevirapine/dt [Drug Therapy];nevirapine/to [Drug Toxicity];penicillamine/cb [Drug Combination];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];phenobarbital/ae [Adverse Drug Reaction];phenobarbital/to [Drug Toxicity];phenytoin/to [Drug Toxicity];polyinosinic polycytidylic acid/cb [Drug Combination];polyinosinic polycytidylic acid/to [Drug Toxicity];polyinosinic polycytidylic acid/pd [Pharmacology];propylthiouracil/dt [Drug Therapy];propylthiouracil/to [Drug Toxicity];prostaglandin E/pd [Pharmacology];ranitidine/to [Drug Toxicity];RNA directed DNA polymerase inhibitor/ae [Adverse Drug Reaction];RNA directed DNA polymerase inhibitor/cb [Drug Combination];RNA directed DNA polymerase inhibitor/cm [Drug Comparison];RNA directed DNA polymerase inhibitor/dt [Drug Therapy];RNA directed DNA polymerase inhibitor/to [Drug Toxicity];sulfamethoxazole/to [Drug Toxicity];sulfonamide/ae [Adverse Drug Reaction];sulfonamide/to [Drug Toxicity];tacrolimus/cb [Drug Combination];tacrolimus/dt [Drug Therapy];tacrolimus/pd [Pharmacology],"Uetrecht, J.",2005,13 Jan,http://dx.doi.org/10.1208/aapsj070489,0,0,
2149,"Essentiality, toxicology and chelation therapy of zinc and copper","Both zinc and copper are essential minerals that are required for various cellular functions. Although these metals are essential, they can be toxic at excess amounts, especially in certain genetic disorders. Zinc and copper homeostasis results from a coordinated regulation by different proteins involved in uptake, excretion and intracellular storage/trafficking of these metals. Apart from zinc transporters (ZnT) families and Cu-ATPase, metallothionein is an important storage protein for zinc and copper. Metallothioneins are intracellular polypeptides with a remarkable ability to bind metallic ions. These proteins bind both essential metals indispensable for the organism and also toxic metals (e.g. cadmium or lead). Metallothioneins play a critical role to maintain zinc and copper homeostasis. In this review, we summarize the toxicity of zinc and copper and the potential treatment for zinc or copper toxicity by zinc- or copper-specific chelators: as well as strategy to up-regulate metallothionein. © 2005 Bentham Science Publishers Ltd.","Copper;Copper chelator;Metallothionein;Oxidative damage;Zinc;Zinc chelator;antioxidant activity;copper metabolism;cytotoxicity;homeostasis;human;molecular mechanics;neuroprotection;nonhuman;oxidative stress;protein binding;protein function;regulatory mechanism;review;stomach disease/si [Side Effect];toxicity/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];zinc metabolism;1 hydroxypyridine 2 thione/pd [Pharmacology];acetylcysteine/pd [Pharmacology];acetylcysteine derivative/pd [Pharmacology];acetylsalicylic acid/pd [Pharmacology];adenosine triphosphatase/ec [Endogenous Compound];antioxidant/pd [Pharmacology];ascorbic acid/pd [Pharmacology];bathocuproinedisulfonic acid/pd [Pharmacology];beta carotene/pd [Pharmacology];chelating agent/ae [Adverse Drug Reaction];chelating agent/cm [Drug Comparison];chelating agent/dt [Drug Therapy];chelating agent/to [Drug Toxicity];chelating agent/pd [Pharmacology];copper/to [Drug Toxicity];deferiprone/cm [Drug Comparison];deferiprone/pd [Pharmacology];edetate calcium/pd [Pharmacology];edetic acid derivative/pd [Pharmacology];glutathione/pd [Pharmacology];manganese n,n' ethylenebis(3 methoxysalicylideneamine)/pd [Pharmacology];metallothionein/to [Drug Toxicity];metallothionein/ec [Endogenous Compound];metallothionein/pd [Pharmacology];n,n,n',n' tetrakis(2 pyridylmethyl)ethylenediaminepentaethylene/cm [Drug Comparison];n,n,n',n' tetrakis(2 pyridylmethyl)ethylenediaminepentaethylene/to [Drug Toxicity];n,n,n',n' tetrakis(2 pyridylmethyl)ethylenediaminepentaethylene/pd [Pharmacology];penicillamine/pd [Pharmacology];pyrithione/cm [Drug Comparison];pyrithione/to [Drug Toxicity];pyrithione/pd [Pharmacology];pyruvate sodium/pd [Pharmacology];s nitrosothiol/pd [Pharmacology];selenium/pd [Pharmacology];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/pd [Pharmacology];thioctic acid/pd [Pharmacology];unclassified drug;unindexed drug;Wilson disease protein/ec [Endogenous Compound];zinc/to [Drug Toxicity];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/cm [Drug Comparison];zinc acetate/dt [Drug Therapy];zinc acetate/pd [Pharmacology];zinc transporter/ec [Endogenous Compound]","Cai, L.;Li, X. K.;Song, Y.;Cherian, M. G.",2005,,http://dx.doi.org/10.2174/092986705774462950,0,0,
2150,Hepatic Wilson's disease: Initial treatment and long-term management,"This article is based on the experience of 320 patients with Wilson's disease who were seen between the years 1954 and 2000. These patients were seen at The Boston City Hospital, 1954 thru 1955, University College Hospital, London, 1955 thru 1957; Addenbrooke's Hospital, Cambridge, 1967 thru 1987, and The Middlesex Hospital London, 1988 thru 2000. Wilson's disease is not strictly a gastroenterologic disease but a genetically determined metabolic disease that is mediated by a failure of copper excretion through the bile. The mutation carried on chromosome 13q14.3: it involves a copper-carrying ATPase (ATPase 7B); more than 250 mutations are now known. The first organ to be affected is the liver, then many other tissues, principally the brain but also the eyes, the kidneys, the bone marrow, and the osteoskeletal system. It is with the hepatic form of the disease that this article is concerned. The hepatic illness may be acute, subacute or chronic; it may be progressive or, apparently, self-limiting. In 10% of patients hemolysis may also be found which can later lead to the formation of pigment gallstones. The management of liver disease is not considered in this article, which is strictly confined to the therapeutic options available for the elimination of copper and the long-term welfare of the patient. It must be remembered that all close relatives of the patient must be screened for the presymptomatic stage of the disease so, if they are found to be homozygous carriers for the mutation, they can be started on preventive treatment. Copyright © 2005 by Current Science Inc.",abdominal pain/si [Side Effect];bile flow;bone marrow depression/si [Side Effect];bone marrow disease;brain disease;breast disease/si [Side Effect];burning sensation/si [Side Effect];chromosome 13q;chromosome mutation;cost effectiveness analysis;cutis laxa/si [Side Effect];disease classification;disease exacerbation/si [Side Effect];drug cost;drug dose regimen;drug potentiation;elastosis/si [Side Effect];epidermolysis bullosa/si [Side Effect];eye disease/si [Side Effect];fever/si [Side Effect];gallstone;genetic analysis;Goodpasture syndrome/si [Side Effect];homozygosity;human;immune complex nephritis/si [Side Effect];injection site abscess/si [Side Effect];injection site pain/si [Side Effect];iron deficiency anemia/si [Side Effect];kidney disease/si [Side Effect];liver disease/di [Diagnosis];liver disease/dm [Disease Management];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/pc [Prevention];liver disease/su [Surgery];liver transplantation;long term care;metabolic disorder;mouth disease/si [Side Effect];mouth ulcer/si [Side Effect];muscle spasm/si [Side Effect];musculoskeletal disease;mutational analysis;nausea/si [Side Effect];neurologic disease/si [Side Effect];nonhuman;portal hypertension/si [Side Effect];review;side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];skin defect/si [Side Effect];stomach irritation/si [Side Effect];sweating;systemic lupus erythematosus/si [Side Effect];taste disorder/si [Side Effect];thorax disease/si [Side Effect];throat disease/si [Side Effect];United Kingdom;university hospital;urticaria/si [Side Effect];vomiting/si [Side Effect];welfare;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/pc [Prevention];Wilson disease/su [Surgery];adenosine triphosphatase/ec [Endogenous Compound];alpha tocopherol/ae [Adverse Drug Reaction];alpha tocopherol/dt [Drug Therapy];amino acid/dt [Drug Therapy];antioxidant/ae [Adverse Drug Reaction];antioxidant/dt [Drug Therapy];ascorbic acid/dt [Drug Therapy];copper/ec [Endogenous Compound];corticosteroid derivative/dt [Drug Therapy];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/do [Drug Dose];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];dimercaprol/pe [Pharmacoeconomics];edetate disodium/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/it [Drug Interaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/po [Oral Drug Administration];pyridoxine/dt [Drug Therapy];tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/cb [Drug Combination];tetrathiomolybdate ammonium/do [Drug Dose];tetrathiomolybdate ammonium/it [Drug Interaction];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/to [Drug Toxicity];tetrathiomolybdate ammonium/pe [Pharmacoeconomics];thiovaline/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/do [Drug Dose];trientine/it [Drug Interaction];trientine/dt [Drug Therapy];trientine/pe [Pharmacoeconomics];unclassified drug;vitamin/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/cm [Drug Comparison];zinc acetate/dt [Drug Therapy];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/cb [Drug Combination];zinc derivative/cm [Drug Comparison];zinc derivative/do [Drug Dose];zinc derivative/it [Drug Interaction];zinc derivative/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy],"Walshe, J. M.",2005,December,http://dx.doi.org/10.1007/s11938-005-0033-9,0,0,
2151,"Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in kidney cells of Long-Evans Cinnamon (LEC) rats","The effects of treatment with trientine, a specific copper-chelating agent, on the accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the kidneys of LEC rats in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, renal copper contents did not increase and were maintained at the same levels as those in 4-week-old LEC rats. Estimation of the amounts of DNA single-strand breaks (SSBs) by comet assay showed that SSBs of DNA were induced in a substantial population of LEC rat renal cortex cells around 12 weeks of age and that the amounts of SSBs increased in an age-dependent manner from 12 to 18 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that SSBs of DNA in LEC rat kidney cells are induced prior to occurrence of clinical signs of hepatic injury and that treatment of LEC rats with trientine decreases the number of DNA strand breaks. Copyright © 2005 Japanese Association for Laboratory Animal Science.",Copper;DNA strand breaks;Kidney cells;LEC rat;Trientine;age;animal cell;animal experiment;animal tissue;article;cell count;comet assay;controlled study;copper metabolism;DNA damage;DNA repair;DNA strand breakage;drug mechanism;kidney cell;kidney cortex;male;nonhuman;rat;rat strain;Wilson disease;trientine/po [Oral Drug Administration];trientine/pd [Pharmacology],"Hayashi, M.;Miyane, K.;Senou, M.;Endoh, D.;Higuchi, H.;Nagahata, H.;Nakayama, K.;Kon, Y.;Okui, T.",2005,20 Dec,http://dx.doi.org/10.1538/expanim.54.403,0,0,
2152,Homozygosity for a gross partial gene deletion of the C-terminal end of ATP7B in a Wilson patient with hepatic and no neurological manifestations,"We identified a partial gene deletion of ATP7B in a patient with Wilson disease with hepatic onset. The deletion covered exon 20 including major parts of the flanking introns. The breakpoints were identified and the size of the deletion determined to be 2144 bp. The deletion is predicted to lead to a mutated protein product containing 45 aberrant amino acids after transmembrane domain 7, and lacking the transmembrane domain 8 as well as the entire C-terminal cytoplasmic tail. This is the first time a partial gene deletion has been demonstrated in ATP7B. The patient presented at age 10 with hepatic manifestations, including severe jaundice, hepato-splenomegaly, ascites, and spider naevi. The liver biopsy showed fibrosis and early signs of cirrhosis. There was a Kayser-Fleischer ring but no neurological manifestations. All symptoms disappeared with penicillamine therapy. This suggests that the C-terminal cytoplasmatic tail of ATP7B, is not essential for its neurological function. Large deletions in ATP7B may be an overlooked cause of Wilson disease. Patients that are homozygotes for deletions maybe valuable for the understanding of the function of various regions of the ATP7B protein. © 2005 Wiley-Liss, Inc.",atp7b;Hepatic type;Molecular diagnosis;Partial gene deletion;Wilson disease;adult;article;ascites;ATP7B gene;carboxy terminal sequence;case report;clinical feature;controlled study;cytoplasm;disease severity;exon;gene;gene deletion;gene mutation;hepatomegaly;homozygosity;homozygote;human;intron;jaundice;liver biopsy;liver cirrhosis/di [Diagnosis];liver fibrosis/di [Diagnosis];male;neurologic disease;nevus;priority journal;protein domain;splenomegaly;symptomatology;treatment outcome;Wilson disease/dt [Drug Therapy];amino acid/ec [Endogenous Compound];gene product;penicillamine/dt [Drug Therapy],"Moller, L. B.;Ott, P.;Lund, C.;Horn, N.",2005,01 Nov,http://dx.doi.org/10.1002/ajmg.a.30977,0,0,
2153,Mowat-Wilson syndrome and mutation of the Zinc Finger Homeo Box 1B gene: A new syndrome probably under-diagnosed,"Objectives. The aim of this study is to increase the awareness of a probably under-diagnosed syndrome. Clinical recognition of the syndrome in infants and children with and without HSCR is important for the selection of patients for cytogenetic and molecular analyses. Methods. The clinical features of four Italian patients are reported. FISH and mutational analyses were performed. Evaluation of psychomotor development was performed using the Denver Developmental Screening Test II (DDTS II). Results. All four patients presented with mutations of the ZFHX1B gene; patients 1, 3 and 4 showed novel mutations, never previously described. The clinical features of our patients were compared with those of the literature. The most frequent malformations were HSCR (62.8%), congenital heart diseases (50.7%), agenesis of the corpus callosum (45.6%). Hypospadias were present in 46.2% of the patients. Seizures were very frequent (75.0%). Conclusions. Mowat-Wilson syndrome is well recognisable, like classical genetic syndromes, for the distinct facial phenotype, the associated malformations, seizures, microcephaly and severe mental retardation. The confirmation of the diagnosis by the presence of mutations in the ZFHX1B gene is important for genetic counselling since all patients thus far reported have been sporadic findings, even if the possibility of gonadal mosaicism cannot be excluded.",hscr;Mental retardation;Mowat-Wilson syndrome;ZFHX1B gene;article;case report;clinical feature;congenital heart disease/cn [Congenital Disorder];congenital heart disease/et [Etiology];corpus callosum agenesis/cn [Congenital Disorder];corpus callosum agenesis/et [Etiology];denver developmental screening test II;disease association;disease severity;female;fluorescence in situ hybridization;gene mutation;genetic counseling;homeobox;human;hypospadias/et [Etiology];infant;Italy;male;mental deficiency;microcephaly;mowat wilson syndrome/cn [Congenital Disorder];mowat wilson syndrome/et [Etiology];phenotype;preschool child;psychomotor development;school child;screening test;seizure/et [Etiology];sex chromosome mosaicism;zinc finger homeobox 1b gene,"Cerruti Mainardi, P.;Garavelli, L.;Pastore, G.;Virdis, R.;Pedori, S.;Godi, M.;Provera, S.;Rauch, A.;Zweier, C.;Castronovo, C.;Zollino, M.;Banchini, G.;Bernasconi, S.;Neri, G.",2005,April,,0,0,
2154,EMG and motor magnetic evoked potentials in patients with Wilson's disease,"We examined four patients with Wilson's disease (WD), mean age of 37,5 years; and with duration of the disease between 2 and 6 years. Diagnosis was made on the basis of copper metabolism examination with significant copper levels in 24 h urine, neurological status, CT of the head, involvement of liver and presence of Kayser-Fleischer ring. All patients underwent complex EMG examination: Blink reflex (BR), cranial and spinal motor Magnetic Evoked Potentials (MEPs) and Nerve Conductive Velocities (NCVs) of the limbs. The first 3 patients (2 women and 1 man) were examined before starting of d-penicillamine therapy and the last patient, a 25 year-old woman with 12-year evolution of WD, after 2 years of Cuprenil treatment. All patients had normal NCVs and spinal MEPs. BR and cranial MEPs were abnormal in 3 untreated patients. The patient with permanent treatment showed nearly normal parameters, except for reduced amplitudes of cranial MEPs. Although our results are preliminary and insufficient for steady conclusion and statistical analysis they do suggest that, by applying specific electrophysiological methods, we could determine clinically latent dysfunctions of central motor neuron, pyramidal tracts and brainstem in WD. There is evidence that some parameters of these tests could be additionally useful in monitoring of the treatment.",Electromyography;Evoked potentials;Hepatolenticular degeneration/diagnosis;Magnetics;adult;article;brain stem;case report;computer assisted tomography;copper blood level;copper metabolism;disease duration;electromyogram;electrophysiology;evoked muscle response;eyelid reflex;female;human;male;motoneuron;nerve conduction;pyramidal tract;statistical analysis;urinalysis;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Klissurski, M. G.;Muradyan, N.;Novachkova, S.;Vassileva, E.;Ishpekova, B.",2005,,,0,0,
2155,Risk and benefit of drug use during pregnancy,"Environmental teratogenic factors (e.g. alcohol) are preventable. We focus our analysis on human teratogenic drugs which are not used frequently during pregnancy. The previous human teratogenic studies had serious methodological problems, e.g. the first trimester concept is outdated because environmental teratogens cannot induce congenital abnormalities in the first month of gestation. In addition, teratogens usually cause specific congenital abnormalities or syndromes. Finally, the importance of chemical structures, administrative routes and reasons for treatment at the evaluation of medicinal products was not considered. On the other hand, in the so-called case-control epidemiological studies in general recall bias was not limited. These biases explain that the teratogenic risk of drugs is exaggerated, while the benefit of medicine use during pregnancy is underestimated. Thus, a better balance is needed between the risk and benefit of drug treatments during pregnancy. Of course, we have to do our best to reduce the risk of teratogenic drugs as much as possible, however, it is worth stressing the preventive effect of drugs for maternal diseases (e.g. diabetes mellitus and hyperthermia) related congenital abnormalities. Copyright© 2005 Ivyspring International Publisher.",Congenital abnormalities;Congenital abnormality;Critical period;Human teratogenic drugs;Preventive effect of drugs;Recall bias;acne/dt [Drug Therapy];case control study;congenital disorder/si [Side Effect];congenital malformation/si [Side Effect];cutis laxa/si [Side Effect];diabetes mellitus;drug megadose;drug use;environmental factor;fetotoxicity/si [Side Effect];fetus risk;first trimester pregnancy;gestation period;goiter/si [Side Effect];human;hyperthermia;leprosy/dt [Drug Therapy];limb defect/si [Side Effect];maternal disease;pregnancy;psoriasis/dt [Drug Therapy];review;risk benefit analysis;side effect/si [Side Effect];syndrome/si [Side Effect];teratogenesis;thrombosis/dt [Drug Therapy];tooth color;Wilson disease/dt [Drug Therapy];alcohol/to [Drug Toxicity];aminoglycoside antibiotic agent/ae [Adverse Drug Reaction];androgen/to [Drug Toxicity];barbital/ae [Adverse Drug Reaction];benzodiazepine/ae [Adverse Drug Reaction];chlorothiazide/ae [Adverse Drug Reaction];clomifene/ae [Adverse Drug Reaction];coumarin derivative/ae [Adverse Drug Reaction];coumarin derivative/dt [Drug Therapy];diazepam/ae [Adverse Drug Reaction];diethylstilbestrol/ae [Adverse Drug Reaction];ergotamine derivative/ae [Adverse Drug Reaction];estrogen/ae [Adverse Drug Reaction];estrogen/do [Drug Dose];etretinate/ae [Adverse Drug Reaction];etretinate/dt [Drug Therapy];flurazepam/ae [Adverse Drug Reaction];furosemide/ae [Adverse Drug Reaction];isotretinoin/ae [Adverse Drug Reaction];isotretinoin/dt [Drug Therapy];oral contraceptive agent/ae [Adverse Drug Reaction];oxytetracycline/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];potassium iodide/ae [Adverse Drug Reaction];povidone iodine/ae [Adverse Drug Reaction];quazepam/ae [Adverse Drug Reaction];retinol/ae [Adverse Drug Reaction];sex hormone/ae [Adverse Drug Reaction];temazepam/ae [Adverse Drug Reaction];teratogenic agent/ae [Adverse Drug Reaction];teratogenic agent/to [Drug Toxicity];tetracycline/ae [Adverse Drug Reaction];thalidomide/ae [Adverse Drug Reaction];thalidomide/dt [Drug Therapy];triazolam/ae [Adverse Drug Reaction];unindexed drug,"Banhidy, F.;Lowry, R. B.;Czeizel, A. E.",2005,01 Jul,,0,0,
2156,Zinc supplementation decreases hepatic copper accumulation in LEC rat: A model of Wilson's disease,"The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content. © Copyright 2005 by Humana Press Inc.",Apoptosis;Copper;Long Evans Cinnamon rat;Metallothionein;Zinc;animal experiment;animal model;animal tissue;article;bile duct carcinoma;bioaccumulation;controlled study;drug effect;female;liver cell damage;liver injury;liver level;liver protection;nonhuman;rat;rat strain;Wilson disease;copper/to [Drug Toxicity];metallothionein/ec [Endogenous Compound];zinc acetate/po [Oral Drug Administration];zinc acetate/pd [Pharmacology],"Esparza Gonzalez, B. R.;Fong, R. N.;Gibson, C. J.;Fuentealba, I. C.;Cherian, M. G.",2005,Summer,http://dx.doi.org/10.1385/BTER:105:1-3:117,0,0,
2157,Genetic disorders of copper transport - Diagnosis and new treatment for the patients of Wilson's disease -. [Japanese],"Wilson's disease and Menkes disease are inherited genetic disorders of copper metabolism. Each disease results from the absence or dysfunction of homologous copper-transporting ATPases present in the trans-Golgi network of cells. The Wilson ATPase transports copper into the hepatocyte secretory pathway for incorporation into ceruloplasmin and excretion into the bile. Thus, patients with Wilson's disease of the autosomal recessive trait present with signs and symptoms arising from impaired biliary copper excretion. The Menkes ATPase transports copper across the placenta, gastrointestinal tract, and blood-brain barrier, and the clinical features of this X-linked disease arise from copper deficiency. Despite striking differences in the clinical presentation of these two diseases, the respective ATPases function in precisely the same fashion within the cell. The different clinical features of each disease are the results of the tissue specific expression of these ATPases. In Wilson's disease, impaired biliary copper excretion leads to accumulation of this metal in the liver. When the capacity for hepatic storage is exceeded, cell death ensues, with copper release into the plasma resulting in hemolysis and deposition of copper in extrahepatic tissues. Affected patients usually present in the first or second decade of life with chronic hepatitis and cirrhosis or acute liver failure. Copper accumulation in the cornea results in Kayser-Fleischer rings. Neuropsychiatric symptoms are more common in adults and include dystonia, tremor, personality changes, and cognitive impairment as a results of copper accumulation in the basal ganglia and other brain regions. The diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper, and elevated hepatic copper concentration. A large number of different mutations occur in the genes of patients with Wilson disease. Copper chelation drugs and zinc are effective in most cases. New treatment guidelines now advise physicians to start patients on zinc.",autosomal recessive disorder;bile flow;blood brain barrier;cell death;chronic hepatitis;clinical feature;conference paper;copper metabolism;disease classification;dystonia;genetic disorder;hemolysis;human;liver cell;liver cirrhosis;liver failure;Menkes syndrome;neuropsychiatry;personality disorder;sequence homology;trans Golgi network;tremor;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adenosine triphosphatase;adenosine triphosphatase 7a;adenosine triphosphatase 7B;ceruloplasmin;chelating agent/dt [Drug Therapy];Menkes protein;unclassified drug;Wilson disease protein;zinc/dt [Drug Therapy],"Aoki, T.",2005,,,0,0,
2158,Movement disorders. [French],,chorea/di [Diagnosis];chorea/et [Etiology];chorea/si [Side Effect];differential diagnosis;disease classification;dystonia;electroencephalogram;hemiballism;human;Huntington chorea/di [Diagnosis];Huntington chorea/et [Etiology];Huntington chorea/si [Side Effect];motor dysfunction/di [Diagnosis];motor dysfunction/et [Etiology];motor dysfunction/si [Side Effect];myoclonus;neuroimaging;parkinsonism/et [Etiology];parkinsonism/si [Side Effect];pathophysiology;review;tardive dyskinesia/et [Etiology];tardive dyskinesia/si [Side Effect];tic;tremor/et [Etiology];tremor/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];anticonvulsive agent/ae [Adverse Drug Reaction];antidepressant agent/ae [Adverse Drug Reaction];antivertigo agent/ae [Adverse Drug Reaction];anxiolytic agent/ae [Adverse Drug Reaction];beta adrenergic receptor blocking agent/ae [Adverse Drug Reaction];caffeine;calcium channel blocking agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];clozapine/ae [Adverse Drug Reaction];flunarizine/ae [Adverse Drug Reaction];immunosuppressive agent/ae [Adverse Drug Reaction];lithium/ae [Adverse Drug Reaction];methyldopa/ae [Adverse Drug Reaction];metoclopramide/ae [Adverse Drug Reaction];neuroleptic agent/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];theophylline/ae [Adverse Drug Reaction];thyroid hormone/ae [Adverse Drug Reaction];thyroid hormone/do [Drug Dose];valproic acid/ae [Adverse Drug Reaction],"Azulay, J. P.",2005,15 Jun,,0,0,
2159,Wilson's disease presenting as status epilepticus,,adolescent;anamnesis;brain cortex;case report;ceruloplasmin blood level;chelation therapy;clinical feature;copper metabolism;creatinine blood level;electroencephalography;electrolyte blood level;epileptic state;female;follow up;gliosis;glucose blood level;human;letter;liver disease;neuropsychiatry;nuclear magnetic resonance imaging;pyridoxine deficiency/et [Etiology];seizure/dt [Drug Therapy];slow brain wave;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;creatinine;glucose;liver enzyme/ec [Endogenous Compound];midazolam/do [Drug Dose];midazolam/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];phenytoin/do [Drug Dose];phenytoin/dt [Drug Therapy];pyridoxine/do [Drug Dose];pyridoxine/dt [Drug Therapy],"Kumar, S.",2005,May,,0,0,
2160,Cognition in liver disease,"Background: Cognitive dysfunction has been observed in a range of liver diseases including chronic hepatitis C virus, alcoholic liver disease, primary biliary cirrhosis and Wilson's disease. Such dysfunction may range from mild cognitive changes to overt hepatic encephalopathy, and represents a significant complication of liver disease that may negatively impact the patient's quality of life, and normal activities of daily living (e.g., driving). Method: This article reviews the published evidence relating to cognitive dysfunction in liver disease. Outcome: Issues of definition, diagnosis, epidemiology, aetiology, treatment and outcome are discussed. Particular attention is devoted to identifying the mild cognitive changes that occur in liver diseases of different aetiology. © Blackwell Munksgaard 2005.",Alcohol;Cognition;Hepatic encephalopathy;Hepatitis C;Liver disease;Neuropsychology;Primary biliary cirrhosis;Wilson's disease;alcohol liver disease;autoimmune hepatitis;clinical trial;cognitive defect/co [Complication];cognitive defect/di [Diagnosis];cognitive defect/dt [Drug Therapy];cognitive defect/ep [Epidemiology];cognitive defect/et [Etiology];cognitive defect/si [Side Effect];cognitive defect/th [Therapy];depression/dt [Drug Therapy];depression/si [Side Effect];diagnostic accuracy;diagnostic value;diet therapy;disease association;disease severity;early diagnosis;hemochromatosis;hepatic encephalopathy/co [Complication];hepatic encephalopathy/di [Diagnosis];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/ep [Epidemiology];hepatic encephalopathy/et [Etiology];hepatic encephalopathy/th [Therapy];hepatitis B;human;incidence;intrahepatic cholestasis;liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver transplantation;mental performance;neuropsychological test;pathogenesis;prediction;prevalence;protein intake;quality of life;review;supplementation;virus hepatitis/dt [Drug Therapy];Wilson disease;antidepressant agent/cb [Drug Combination];antidepressant agent/dt [Drug Therapy];branched chain amino acid/ct [Clinical Trial];branched chain amino acid/dt [Drug Therapy];branched chain amino acid/po [Oral Drug Administration];interferon/ae [Adverse Drug Reaction];interferon/cb [Drug Combination];interferon/dt [Drug Therapy];lactulose/ct [Clinical Trial];lactulose/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Collie, A.",2005,February,http://dx.doi.org/10.1111/j.1478-3231.2005.01012.x,0,0,
2161,Huntington's disease and related disorders,"Numerous conditions are known to produce movement abnormalities, including chorea, along with cognitive and psychiatric symptoms. HD has received the most clinical and research attention, in part because of the availability of precise genetic testing, but commercial genetic tests are available for several other conditions, including SCAs. Genetic testing is helpful in some trinucleotide repeat disorders, but the impact of testing on the patient and family should be assessed. Degeneration of the basal ganglia is seen in several of these conditions, and may account for some of the behavioral changes, especially deficits in impulse control, motivation, and executive function, along with motor symptoms. Because many of the conditions discussed can present with similar motor and behavioral symptoms, a careful family history, examination, and select use of laboratory tests may be needed if the diagnosis is in question. Psychiatric symptoms are common in these disorders, and may cause comparable disability to that caused by the movement disorder itself. There is little research on treatment of psychiatric conditions in these disorders, but standard therapies may be useful and should be tried if necessary.",acanthocytosis;chorea/dt [Drug Therapy];clinical feature;cognition;cognitive defect/co [Complication];disease exacerbation/si [Side Effect];extrapyramidal syndrome;genetic counseling;heredity;human;Huntington chorea/et [Etiology];impulse control disorder;liver dysfunction/si [Side Effect];Machado Joseph disease;mental disease/co [Complication];mental disease/dt [Drug Therapy];motivation;motor dysfunction;neurologic disease/co [Complication];neuropathology;nonhuman;priority journal;review;side effect/si [Side Effect];spinocerebellar degeneration/ep [Epidemiology];spinocerebellar degeneration/et [Etiology];trinucleotide repeat;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];caspase inhibitor/dt [Drug Therapy];caspase inhibitor/pd [Pharmacology];creatine/dt [Drug Therapy];creatine/pd [Pharmacology];dopamine receptor blocking agent/ae [Adverse Drug Reaction];dopamine receptor blocking agent/dt [Drug Therapy];lamotrigine/dt [Drug Therapy];lamotrigine/pd [Pharmacology];minocycline/dt [Drug Therapy];minocycline/pd [Pharmacology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];psychotropic agent/ae [Adverse Drug Reaction];psychotropic agent/dt [Drug Therapy];remacemide/dt [Drug Therapy];remacemide/pd [Pharmacology];ubidecarenone/dt [Drug Therapy];ubidecarenone/pd [Pharmacology],"Anderson, K. E.",2005,March,http://dx.doi.org/10.1016/j.psc.2004.10.001,0,0,
2162,Movement disorders: Overview and treatment options,"The authors review therapies for essential tremor, Parkinson's disease, dystonia, myoclonus, chorea, tic disorders, tardive dyskinesia and akasthisia, restless limbs syndrome, and Wilson's disease.",abdominal cramp/si [Side Effect];akathisia/dt [Drug Therapy];ataxia/si [Side Effect];bone marrow suppression/si [Side Effect];bradycardia/si [Side Effect];brain depth stimulation;bronchospasm/si [Side Effect];chorea/dt [Drug Therapy];clinical trial;cognitive defect/si [Side Effect];confusion/si [Side Effect];constipation/si [Side Effect];dementia/dt [Drug Therapy];depression/dt [Drug Therapy];depression/si [Side Effect];dermatitis/si [Side Effect];diarrhea/si [Side Effect];disease classification;dry eye/si [Side Effect];dyskinesia/si [Side Effect];dystonia/dt [Drug Therapy];essential tremor/dt [Drug Therapy];essential tremor/su [Surgery];essential tremor/th [Therapy];fatigue/si [Side Effect];gastrointestinal disease/si [Side Effect];hallucination/si [Side Effect];human;hyperkinesia/dt [Drug Therapy];hypokinesia/dt [Drug Therapy];hypotension/si [Side Effect];impotence/si [Side Effect];insomnia/si [Side Effect];leg edema/si [Side Effect];liver failure/si [Side Effect];lung fibrosis/si [Side Effect];motor dysfunction/dt [Drug Therapy];motor dysfunction/su [Surgery];motor dysfunction/th [Therapy];myoclonus/dt [Drug Therapy];nausea/si [Side Effect];orthostatic hypotension/dt [Drug Therapy];pancreatitis/si [Side Effect];paresthesia/si [Side Effect];Parkinson disease/dt [Drug Therapy];Parkinson disease/su [Surgery];Parkinson disease/th [Therapy];parkinsonism/si [Side Effect];proteinuria/si [Side Effect];psychosis/dt [Drug Therapy];restless legs syndrome/dt [Drug Therapy];review;side effect/si [Side Effect];sleep apnea syndrome/si [Side Effect];sleep disorder/dt [Drug Therapy];sleep disorder/si [Side Effect];somnolence/si [Side Effect];tardive dyskinesia/si [Side Effect];thalamotomy;tic/dt [Drug Therapy];tremor/dt [Drug Therapy];tremor/su [Surgery];tremor/th [Therapy];urinary urgency/dt [Drug Therapy];urine retention/si [Side Effect];vivid dream/si [Side Effect];weight reduction;Wilson disease/dt [Drug Therapy];xerostomia/si [Side Effect];yawning;amantadine/ae [Adverse Drug Reaction];amantadine/do [Drug Dose];amantadine/dt [Drug Therapy];apomorphine/ae [Adverse Drug Reaction];apomorphine/do [Drug Dose];apomorphine/dt [Drug Therapy];baclofen/dt [Drug Therapy];benserazide/dt [Drug Therapy];benzatropine/ae [Adverse Drug Reaction];benzatropine/do [Drug Dose];benzatropine/dt [Drug Therapy];benzatropine mesilate/dt [Drug Therapy];benzodiazepine/ae [Adverse Drug Reaction];benzodiazepine/do [Drug Dose];benzodiazepine/dt [Drug Therapy];carbidopa/ae [Adverse Drug Reaction];carbidopa/cb [Drug Combination];carbidopa/dt [Drug Therapy];carbidopa plus levodopa;clobazam/ae [Adverse Drug Reaction];clobazam/do [Drug Dose];clobazam/dt [Drug Therapy];clonazepam/ae [Adverse Drug Reaction];clonazepam/do [Drug Dose];clonazepam/dt [Drug Therapy];clonidine/ae [Adverse Drug Reaction];clonidine/do [Drug Dose];clonidine/dt [Drug Therapy];clozapine/ae [Adverse Drug Reaction];clozapine/do [Drug Dose];clozapine/dt [Drug Therapy];diazepam;domperidone/ae [Adverse Drug Reaction];domperidone/do [Drug Dose];domperidone/dt [Drug Therapy];donepezil/ae [Adverse Drug Reaction];donepezil/do [Drug Dose];donepezil/dt [Drug Therapy];dopamine receptor stimulating agent/ae [Adverse Drug Reaction];dopamine receptor stimulating agent/ct [Clinical Trial];dopamine receptor stimulating agent/cm [Drug Comparison];dopamine receptor stimulating agent/dt [Drug Therapy];entacapone/ae [Adverse Drug Reaction];entacapone/do [Drug Dose];entacapone/dt [Drug Therapy];etiracetam/ae [Adverse Drug Reaction];etiracetam/do [Drug Dose];etiracetam/dt [Drug Therapy];fludrocortisone/ae [Adverse Drug Reaction];fludrocortisone/do [Drug Dose];fludrocortisone/dt [Drug Therapy];fludrocortisone acetate/dt [Drug Therapy];gabapentin/ae [Adverse Drug Reaction];gabapentin/do [Drug Dose];gabapentin/dt [Drug Therapy];galantamine/ae [Adverse Drug Reaction];galantamine/do [Drug Dose];galantamine/dt [Drug Therapy];glial cell line derived neurotrophic factor/ct [Clinical Trial];glial cell line derived neurotrophic factor/dt [Drug Therapy];glycopyrronium bromide/ae [Adverse Drug Reaction];glycopyrronium bromide/do [Drug Dose];glycopyrronium bromide/dt [Drug Therapy];guanfacine/dt [Drug Therapy];haloperidol/ae [Adverse Drug Reaction];haloperidol/do [Drug Dose];haloperidol/dt [Drug Therapy];konopin;levodopa/ae [Adverse Drug Reaction];levodopa/ct [Clinical Trial];levodopa/cb [Drug Combination];levodopa/cm [Drug Comparison];levodopa/dt [Drug Therapy];levodopa/pk [Pharmacokinetics];memantine/dt [Drug Therapy];metoclopramide/dt [Drug Therapy];midodrine/ae [Adverse Drug Reaction];midodrine/do [Drug Dose];midodrine/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/do [Drug Dose];neuroleptic agent/dt [Drug Therapy];olanzapine/ae [Adverse Drug Reaction];olanzapine/do [Drug Dose];olanzapine/dt [Drug Therapy];oxybutynin/ae [Adverse Drug Reaction];oxybutynin/do [Drug Dose];oxybutynin/dt [Drug Therapy];parlopa;penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];pergolide/ae [Adverse Drug Reaction];pergolide/do [Drug Dose];pergolide/dt [Drug Therapy];pimozide/ae [Adverse Drug Reaction];pimozide/do [Drug Dose];pimozide/dt [Drug Therapy];placebo;pramipexole/ae [Adverse Drug Reaction];pramipexole/do [Drug Dose];pramipexole/dt [Drug Therapy];prazosin/ae [Adverse Drug Reaction];prazosin/do [Drug Dose];prazosin/dt [Drug Therapy];primidone/ae [Adverse Drug Reaction];primidone/ad [Drug Administration];primidone/cb [Drug Combination];primidone/do [Drug Dose];primidone/dt [Drug Therapy];prochlorperazine/dt [Drug Therapy];prochlorperazine maleate;promethazine/dt [Drug Therapy];propranolol/ae [Adverse Drug Reaction];propranolol/ad [Drug Administration];propranolol/cb [Drug Combination];propranolol/do [Drug Dose];propranolol/dt [Drug Therapy];quetiapine/ae [Adverse Drug Reaction];quetiapine/do [Drug Dose];quetiapine/dt [Drug Therapy];rasagiline/dt [Drug Therapy];reserpine/ae [Adverse Drug Reaction];reserpine/do [Drug Dose];reserpine/dt [Drug Therapy];risperidone/ae [Adverse Drug Reaction];risperidone/do [Drug Dose];risperidone/dt [Drug Therapy];rivastigmine/ae [Adverse Drug Reaction];rivastigmine/do [Drug Dose];rivastigmine/dt [Drug Therapy];ropinirole/ae [Adverse Drug Reaction];ropinirole/do [Drug Dose];ropinirole/dt [Drug Therapy];selegiline/ae [Adverse Drug Reaction];selegiline/do [Drug Dose];selegiline/dt [Drug Therapy];selegiline/pd [Pharmacology];terazosin/ae [Adverse Drug Reaction];terazosin/do [Drug Dose];terazosin/dt [Drug Therapy];tetrabenazine/ae [Adverse Drug Reaction];tetrabenazine/do [Drug Dose];tetrabenazine/dt [Drug Therapy];tolcapone/ae [Adverse Drug Reaction];tolcapone/do [Drug Dose];tolcapone/dt [Drug Therapy];tolterodine/ae [Adverse Drug Reaction];tolterodine/do [Drug Dose];tolterodine/dt [Drug Therapy];topiramate/ae [Adverse Drug Reaction];topiramate/do [Drug Dose];topiramate/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trihexyphenidyl/ae [Adverse Drug Reaction];trihexyphenidyl/do [Drug Dose];trihexyphenidyl/dt [Drug Therapy];trimethobenzamide;ubidecarenone/do [Drug Dose];ubidecarenone/dt [Drug Therapy];unclassified drug;valproic acid/ae [Adverse Drug Reaction];valproic acid/do [Drug Dose];valproic acid/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy],"Samii, A.;Ransom, B. R.",2005,April,,0,0,
2163,Wilson disease: High prevalence in a mountaineous area of crete,"Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The disorder is caused by mutations in the ATP7B gene, encoding a copper transporting P-type ATPase. The worldwide incidence is in the order of 30 cases per million, with a gene frequency of 0.56% and a carrier frequency of 1 in 90. The increased number of Wilson disease patients in the island of Crete led us to study the spectrum of mutations in a small village close to the city of Heraklion, from where many patients have been referred during the last 25 years. In order to estimate the frequency of the disease, we firstly investigated the number of births and the number of WD patients in the village since 1978. Six out of 90 births were diagnosed as WD patients, presenting the highest prevalence of WD reported so far. Analysis of the whole gene in three Wilson disease patients, and relatives of a boy who died from WD, led to the detection of 4 different point mutations. Two of them were missense (p.I1148T and p.G1176R) and cosegregated in cis in the same patient; the other allele of this patient carried a nonsense mutation (p.Q289X). This is the first report in the literature of three mutations co-segregating in the same WD patient. The fourth mutation identified was a novel frameshift mutation (c.398delT) with documented cosegregation. When screening 200 inhabitants originating from the same area, 18 were found to be carriers of one of these mutations. These findings indicate the need for health education intervention, genetic counselling and newborn screening for the Wilson disease. © University College London 2005.",ATP7B gene;Crete;Founder effect;Mutation;Wilson disease;adolescent;allele;article;autosomal recessive disorder;cause of death;chelation therapy;child;clinical feature;copper metabolism;diagnostic value;early diagnosis;fatty liver/di [Diagnosis];female;frameshift mutation;gene frequency;genetic counseling;genetic screening;Greece;health education;hepatomegaly/co [Complication];hepatomegaly/dt [Drug Therapy];hepatosplenomegaly/co [Complication];hepatosplenomegaly/dt [Drug Therapy];heterozygote detection;histology;human;incidence;liver biopsy;liver failure/co [Complication];liver failure/dt [Drug Therapy];liver failure/su [Surgery];liver fibrosis/di [Diagnosis];liver transplantation;male;missense mutation;mutational analysis;newborn screening;nonsense mutation;onset age;pedigree analysis;point mutation;prevalence;prevention and control;priority journal;refusal to participate;Wilson disease/di [Diagnosis];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];spironolactone/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Dedoussis, G. V. Z.;Genschel, J.;Sialvera, T. E.;Bochow, B.;Manolaki, N.;Manios, Y.;Tsafantakis, E.;Schmidt, H.",2005,May,http://dx.doi.org/10.1046/j.1529-8817.2005.00171.x,0,0,
2164,The role of copper in tumour angiogenesis,"Copper stimulates the proliferation and migration of endothelial cells and is required for the secretion of several angiogenic factors by tumour cells. Copper chelation decreases the secretion of many of these factors. Serum copper levels are upregulated in many human tumours and correlate with tumour burden and prognosis. Copper chelators reduce tumour growth and microvascular density in animal models. New orally active copper chelators have enabled clinical trials to be undertaken, and there are several studies ongoing. A unifying mechanism of action by which copper chelation inhibits endothelial cell proliferation and tumour secretion of angiogenic factors remains to be elucidated, but possible targets include copper-dependent enzymes, chaperones, and transporters. © Springer Science + Business Media, Inc. 2006.",Angiogenesis;Copper chelation;Copper-dependent enzymes;Tetrathiomolybdate;antineoplastic activity;article;breast cancer/dt [Drug Therapy];cancer cell culture;cell migration;cell proliferation;cell stimulation;chelation therapy;clinical trial;colorectal carcinoma/dt [Drug Therapy];copper blood level;copper metabolism;correlation analysis;drug potentiation;drug structure;drug targeting;endothelium cell;glioma/dt [Drug Therapy];gliosarcoma/dt [Drug Therapy];head and neck tumor/dt [Drug Therapy];hematologic malignancy/dt [Drug Therapy];human;kidney cancer/dt [Drug Therapy];liver cell carcinoma/dt [Drug Therapy];lung cancer/dt [Drug Therapy];mesothelioma/dt [Drug Therapy];metastasis/co [Complication];metastasis/dt [Drug Therapy];microvascularization;nonhuman;prognosis;protein blood level;signal transduction;solid tumor/dt [Drug Therapy];tumor cell;tumor growth;upregulation;Wilson disease/dt [Drug Therapy];amine oxidase (copper containing)/ec [Endogenous Compound];angiogenesis inhibitor/cb [Drug Combination];angiogenesis inhibitor/dt [Drug Therapy];angiogenic factor/ec [Endogenous Compound];atn 224/ct [Clinical Trial];atn 224/an [Drug Analysis];atn 224/dt [Drug Therapy];ceruloplasmin/cb [Drug Combination];ceruloplasmin/it [Drug Interaction];ceruloplasmin/ec [Endogenous Compound];ceruloplasmin/pd [Pharmacology];chaperone/ec [Endogenous Compound];chelating agent/ct [Clinical Trial];chelating agent/an [Drug Analysis];chelating agent/cb [Drug Combination];chelating agent/cr [Drug Concentration];chelating agent/it [Drug Interaction];chelating agent/dt [Drug Therapy];chelating agent/po [Oral Drug Administration];chelating agent/pd [Pharmacology];copper/ct [Clinical Trial];copper/an [Drug Analysis];copper/cb [Drug Combination];copper/it [Drug Interaction];copper/dt [Drug Therapy];copper/ec [Endogenous Compound];copper/po [Oral Drug Administration];copper/pd [Pharmacology];copper zinc superoxide dismutase/ec [Endogenous Compound];cytochrome c oxidase/ec [Endogenous Compound];doxorubicin/cb [Drug Combination];doxorubicin/it [Drug Interaction];doxorubicin/dt [Drug Therapy];hypoxia inducible factor 1/ec [Endogenous Compound];immunoglobulin enhancer binding protein/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];messenger RNA/ec [Endogenous Compound];methotrexate/cb [Drug Combination];methotrexate/dt [Drug Therapy];penicillamine/ct [Clinical Trial];penicillamine/cb [Drug Combination];penicillamine/it [Drug Interaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];prostaglandin E1/cb [Drug Combination];prostaglandin E1/it [Drug Interaction];prostaglandin E1/pd [Pharmacology];protein lysine 6 oxidase/ec [Endogenous Compound];tamoxifen/dt [Drug Therapy];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound],"Lowndes, S. A.;Harris, A. L.",2005,October,http://dx.doi.org/10.1007/s10911-006-9003-7,0,0,
2165,Activities of the COMP. [German],,acromegaly/dt [Drug Therapy];adenomatous polyp/dt [Drug Therapy];adrenal hyperplasia/dt [Drug Therapy];Barrett esophagus;biotechnology;chronic myeloid leukemia/dt [Drug Therapy];digestive system cancer/dt [Drug Therapy];drug indication;Duchenne muscular dystrophy/dt [Drug Therapy];Fabry disease/cn [Congenital Disorder];Fabry disease/dt [Drug Therapy];Friedreich ataxia/dt [Drug Therapy];Gaucher disease/dt [Drug Therapy];Germany;human;Hurler syndrome/cn [Congenital Disorder];Hurler syndrome/dt [Drug Therapy];leishmaniasis/dt [Drug Therapy];liver carcinoma/dt [Drug Therapy];liver cell carcinoma/dt [Drug Therapy];meconium aspiration/dt [Drug Therapy];pancreas carcinoma/dt [Drug Therapy];Parkinson disease/dt [Drug Therapy];patent ductus arteriosus/cn [Congenital Disorder];patent ductus arteriosus/dt [Drug Therapy];Peyronie disease/dt [Drug Therapy];promyelocytic leukemia/dt [Drug Therapy];rare disease/dt [Drug Therapy];short survey;thrombocythemia/dt [Drug Therapy];tyrosinemia/cn [Congenital Disorder];tyrosinemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase beta/dt [Drug Therapy];anagrelide/dt [Drug Therapy];arsenic trioxide/dt [Drug Therapy];bosentan/dt [Drug Therapy];busulfan/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];carglumic acid/dt [Drug Therapy];celecoxib/dt [Drug Therapy];cladribine/dt [Drug Therapy];dudopa;hydrocortisone/dt [Drug Therapy];ibuprofen/dt [Drug Therapy];ibuprofen lysine/dt [Drug Therapy];idebenone/dt [Drug Therapy];iloprost/dt [Drug Therapy];imatinib/dt [Drug Therapy];imexon/dt [Drug Therapy];laronidase/dt [Drug Therapy];litak;melatonin/dt [Drug Therapy];miglustat/dt [Drug Therapy];miltefosine/dt [Drug Therapy];mitotane/dt [Drug Therapy];n (methyldiazacyclo hexylmethylbenzamide)azaphenylaminothiopyrrole/dt [Drug Therapy];nemorubicin/dt [Drug Therapy];nitisinone/dt [Drug Therapy];omega conotoxin MVIIA/dt [Drug Therapy];orphan drug/dt [Drug Therapy];pegvisomant/dt [Drug Therapy];photofrin/dt [Drug Therapy];unclassified drug;wilzin;zinc acetate/dt [Drug Therapy],"Throm, S.",2005,,,0,0,
2166,Liver disorders during pregnancy,* During pregnancy a woman's albumin level normally decreases and her alkaline phosphatase level normally increase. * Abnormal transaminase levels and prothrombin time indicate liver pathology. * Think of cholestasis in pregnancy in women with an itch in late pregnancy; check the bile acids. * Development of nausea and abdominal pain in late pregnancy could indicate serious liver problems. * Pregnant and postpartum women have an increased risk of cholelithiasis.,abdominal pain;albumin blood level;alcohol liver disease;alkaline phosphatase blood level;aminotransferase blood level;article;bile acid blood level;Budd Chiari syndrome;cholelithiasis;cholestasis/dt [Drug Therapy];chronic active hepatitis/dt [Drug Therapy];drug contraindication;enzyme deficiency;esophagus varices/dt [Drug Therapy];fatty acid oxidation;fatty liver;female;HELLP syndrome;hepatitis A;hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];hepatitis C/dt [Drug Therapy];hepatitis E;herpes simplex/dt [Drug Therapy];high risk population;human;hyperemesis gravidarum;liver adenoma;liver cirrhosis;liver disease/dt [Drug Therapy];liver disease/si [Side Effect];liver function test;liver hyperplasia;liver toxicity/si [Side Effect];nausea;nonalcoholic fatty liver;portal hypertension;preeclampsia;pregnancy;prothrombin time;pruritus;puerperium;third trimester pregnancy;virus hepatitis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];3 hydroxyacyl coenzyme A dehydrogenase/ec [Endogenous Compound];aciclovir/dt [Drug Therapy];aciclovir/iv [Intravenous Drug Administration];acihexal;alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];beta adrenergic receptor blocking agent/dt [Drug Therapy];bile acid/ec [Endogenous Compound];bile salt/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];cholesterol/ec [Endogenous Compound];d penamine;dexamethasone sodium phosphate/iv [Intravenous Drug Administration];fatty acid/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];globulin/ec [Endogenous Compound];hepatitis B antibody/dt [Drug Therapy];hepatitis B vaccine/dt [Drug Therapy];hepatitis C vaccine/dt [Drug Therapy];herbaceous agent/ae [Adverse Drug Reaction];immunosuppressive agent/dt [Drug Therapy];peginterferon/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prothrombin/ec [Endogenous Compound];ribavirin/dt [Drug Therapy];triacylglycerol/ec [Endogenous Compound];unclassified drug/ae [Adverse Drug Reaction];ursodeoxycholic acid/dt [Drug Therapy],"McDonald, J.",2005,September,,0,0,
2167,"Copper, oxidative stress, and human health","Copper (Cu), a redox active metal, is an essential nutrient for all species studied to date. During the past decade, there has been increasing interest in the concept that marginal deficits of this element can contribute to the development and progression of a number of disease states including cardiovascular disease and diabetes. Deficits of this nutrient during pregnancy can result in gross structural malformations in the conceptus, and persistent neurological and immunological abnormalities in the offspring. Excessive amounts of Cu in the body can also pose a risk. Acute Cu toxicity can result in a number of pathologies, and in severe cases, death. Chronic Cu toxicity can result in liver disease and severe neurological defects. The concept that elevated ceruloplasmin is a risk factor for certain diseases is discussed. In this paper, we will review recent literature on the potential causes of Cu deficiency and Cu toxicity, and the pathological consequences associated with the above. Finally, we will review some of the potential biochemical lesions that might underlie these pathologies. Given that oxidative stress is a characteristic of Cu deficiency, the role of Cu in the oxidative defense system will receive special attention. The concept that excess Cu may be a precipitating factor in Alzheimer's disease is discussed. © 2005 Elsevier Ltd. All rights reserved.",Alzheimer's disease;Cardiovascular disease;Ceruloplasmin;Cu deficiency;Cu toxicity;Diabetes;Metallothionein;Nitric oxide;Oxidant defense system;Oxidative damage;Oxidative stress;Pregnancy;Superoxide dismutase;Alzheimer disease/et [Etiology];antineoplastic activity;cardiovascular disease/et [Etiology];cell protection;chronic disease;clinical feature;common cold/dt [Drug Therapy];copper deficiency/si [Side Effect];copper metabolism;diabetes mellitus/et [Etiology];diet supplementation;disease association;disease predisposition;enzyme activity;flu like syndrome/dt [Drug Therapy];health status;human;hypercholesterolemia/dt [Drug Therapy];neovascularization (pathology);nitration;nonhuman;pathogenesis;pathophysiology;pregnancy complication/et [Etiology];protein expression;protein function;review;risk assessment;risk factor;toxicity;Wilson disease/et [Etiology];buthionine sulfoximine/dt [Drug Therapy];catalase;chelating agent/ae [Adverse Drug Reaction];chelating agent/pd [Pharmacology];copper/to [Drug Toxicity];copper zinc superoxide dismutase;diethyldithiocarbamic acid;doxorubicin;glutathione;glutathione peroxidase;manganese superoxide dismutase;penicillamine/ae [Adverse Drug Reaction];penicillamine/pd [Pharmacology];reactive oxygen metabolite;selenium;tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/pd [Pharmacology];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity],"Uriu-Adams, J. Y.;Keen, C. L.",2005,August/October,http://dx.doi.org/10.1016/j.mam.2005.07.015,0,0,
2168,Extensive cortico-subcortical lesions in Wilson's disease: Clinico-pathological study of two cases,"Wilson's disease (WD) with extensive cortico-subcortical lesions represents a rare neuropathological subgroup, the pathogenesis of which is not clearly determined. We report two new cases with identical lesions. In the families of each of the patient, there were mutations in the ATPase7B gene, especially in the family of proband 1, and in the first cousin of proband 2. These cases included massive destruction of the white matter in superior gyri, mostly frontal, extending to the deep cortex with neuronal loss and capillary proliferation. Astrocytes were of Alzheimer type 1 and 2; and type 1 were labeled by anti-metallothionein. Opalski cells were abundant and their macrophagic lineage was confirmed by immunostaining. Among the possible mechanisms proposed, the role of vascular factors and penicillamine treatment could be excluded. Cerebral copper content in white matter and putamen of case 1 was at the same level as in common WD but accumulation of unbound copper in the white matter was a distinctive feature, which suggested a pathological neurotoxic effect. © Springer-Verlag 2005.",ATPase7B;Copper;Mitochondria;Whitematter necrosis;Wilson's disease;adult;article;astrocyte;brain cortex lesion/dt [Drug Therapy];brain cortex lesion/et [Etiology];case report;clinical feature;clinical protocol;computer assisted tomography;copper metabolism;death;disease exacerbation/si [Side Effect];female;gene mutation;human;human tissue;immunohistochemistry;male;molecular genetics;nuclear magnetic resonance imaging;pathogenesis;pedigree analysis;priority journal;pyramidal sign;white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];thiamine/cb [Drug Combination];thiamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Mikol, J.;Vital, C.;Wassef, M.;Chappuis, P.;Poupon, J.;Lecharpentier, M.;Woimant, F.",2005,November,http://dx.doi.org/10.1007/s00401-005-1061-1,0,0,
2169,Isolated tongue involvement - An unusual presentation of Wilson's disease [4],,anamnesis;case report;clinical feature;dystonia/di [Diagnosis];dystonia/dt [Drug Therapy];female;human;laboratory test;letter;neurologic examination;physical examination;school child;slit lamp;tongue disease/di [Diagnosis];tongue disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chlorpromazine/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy],"Kumar, T. S.;Moses, P. D.",2005,October,,0,0,
2170,Approach to renal tubular disorders,"The renal tubule plays an important role in fluid and electrolyte homeostasis. Renal tubular disorders may affect multiple (e.g., Fanconi syndrome) or specific (e.g., nephrpgenic diabetes insipidus, renal glucosuria) tubular functions. Most conditions are primary and monogenic but occasionally are secondary to other disorders (focal segmental glomerulosclerosis, cystinosis, Lowe syndrome). Tubular dysfunction should be considered in all children with failure to thrive, polyuria, refractory rickets, hypokalemia and metabolic acidosis. Careful clinical and laboratory evaluation is essential for appropriate diagnosis and specific management of these conditions.",Hypercalciuria;Polyuria;Renal tubular acidosis;bicarbonate blood level;calcium intake;clinical examination;clinical feature;conference paper;cystinosis/dt [Drug Therapy];diagnostic accuracy;diagnostic test;electrolyte balance;evaluation;fluid balance;galactosemia;human;hypercalciuria/dt [Drug Therapy];hypokalemia/dt [Drug Therapy];kidney tubule;kidney tubule disorder/dt [Drug Therapy];laboratory test;metabolic acidosis/dt [Drug Therapy];polyuria/dt [Drug Therapy];treatment planning;urinalysis;urine acidification;urine pH;water deprivation;Wilson disease/dt [Drug Therapy];bicarbonate/dt [Drug Therapy];citrate potassium/dt [Drug Therapy];citrate potassium/po [Oral Drug Administration];indometacin/dt [Drug Therapy];mercaptamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];thiazide diuretic agent/dt [Drug Therapy];vitamin D,"Bagga, A.;Bajpai, A.;Menon, S.",2005,September,,0,0,
2171,Neuroferritinopathy: Missense mutation in FTL causing early-onset bilateral pallidal involvement,"The authors identified a missense mutation in the FTL gene (474G>A; A96T) in a 19-year-old man with parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit, and episodic psychosis. This mutation was also present in his asymptomatic mother and younger brother, who had abnormally low levels of ferritin in the serum. The patient and his mother displayed bilateral involvement of the pallidum. Copyright © 2005 by AAN Enterprises, Inc.",adult;article;autosomal dominant disorder/cn [Congenital Disorder];autosomal dominant disorder/di [Diagnosis];autosomal dominant disorder/et [Etiology];case report;colorimetry;follow up;gene;gene mutation;globus pallidus;human;immunoassay;male;missense mutation;nephelometry;neuroferritinopathy/cn [Congenital Disorder];neuroferritinopathy/di [Diagnosis];neuroferritinopathy/et [Etiology];neurologic examination;nuclear magnetic resonance imaging;polymerase chain reaction;priority journal;psychosis;restriction fragment length polymorphism;Wilson disease;alanine/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];DNA/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];iron/ec [Endogenous Compound];neuroleptic agent;penicillamine;polypeptide/ec [Endogenous Compound];transferrin/ec [Endogenous Compound];trazodone;valproic acid,"Maciel, P.;Cruz, V. T.;Constante, M.;Iniesta, I.;Costa, M. C.;Gallati, S.;Sousa, N.;Sequeiros, J.;Coutinho, P.;Santos, M. M.",2005,23 Aug,http://dx.doi.org/10.1212/01.wnl.0000178224.81169.c2,0,0,
2172,Orphan medicinal products in Europe. [French],"Incentives provided by the 1999 European regulation for the development of orphan drugs are described, and a picture of their outcome 5 years after is shown.",chronic myeloid leukemia/dt [Drug Therapy];conference paper;drug research;Europe;Fabry disease/dt [Drug Therapy];Gaucher disease/dt [Drug Therapy];human;law;prevalence;promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];thrombocythemia/dt [Drug Therapy];treatment outcome;tyrosinemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/pr [Pharmaceutics];agalsidase beta/dt [Drug Therapy];agalsidase beta/pr [Pharmaceutics];anagrelide/dt [Drug Therapy];anagrelide/pr [Pharmaceutics];arsenic trioxide/dt [Drug Therapy];arsenic trioxide/pr [Pharmaceutics];bosentan/dt [Drug Therapy];bosentan/pr [Pharmaceutics];busulfan/dt [Drug Therapy];busulfan/pr [Pharmaceutics];carglumic acid/dt [Drug Therapy];carglumic acid/pr [Pharmaceutics];celecoxib/dt [Drug Therapy];celecoxib/pr [Pharmaceutics];cladribine/dt [Drug Therapy];cladribine/pr [Pharmaceutics];dudopa;fabrizyme;ibuprofen/dt [Drug Therapy];ibuprofen/pr [Pharmaceutics];iloprost/dt [Drug Therapy];iloprost/pr [Pharmaceutics];imatinib/dt [Drug Therapy];imatinib/pr [Pharmaceutics];impavida;laronidase/dt [Drug Therapy];laronidase/pr [Pharmaceutics];litak;mitotane/dt [Drug Therapy];mitotane/pr [Pharmaceutics];nitisinone/dt [Drug Therapy];nitisinone/pr [Pharmaceutics];orphan drug/dt [Drug Therapy];orphan drug/pr [Pharmaceutics];photofrin/dt [Drug Therapy];photofrin/pr [Pharmaceutics];prigit/dt [Drug Therapy];prigit/pr [Pharmaceutics];somovert/dt [Drug Therapy];somovert/pr [Pharmaceutics];unclassified drug;wilzin;zavesco;zinc acetate/dt [Drug Therapy];zinc acetate/pr [Pharmaceutics],"Heron, E.",2005,November,,0,0,
2173,Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans Cinnamon rats,"Objectives: Long-Evans Cinnamon (LEC) rats are characterized by an abnormal hepatic deposition of copper (Cu) due to a lack of the Cu-transporter P-type adenosine triphosphatase: accordingly, the strain is a good animal model of Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the development of acute hepatitis and the biochemical parameters of Cu-induced liver damage was studied in 5-week-old LEC rats (n = 52). Methods: Rats receiving 50 or 80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks after the start of treatment. Results: Treatment with Zn acetate resulted in the prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and symptoms compatible with acute hepatitis between the 6th and 7th week of treatment. Tissue metallothionein (MT) significantly increased in the treated rats and positively correlated with Zn concentrations within the liver. Control rats had a significantly higher iron concentration in the liver and kidneys compared with supplemented rats, after both short- and long-term experiments. 8-hydroxy-2'-deoxyguanosine amounts were significantly lower in untreated rats. Conclusions: Zn acetate prevents acute hepatitis, by increasing tissue MT concentrations, reducing Cu absorption and interfering with Fe metabolism. © Blackwell Munksgaard 2005.",LEC rats;Metallothionein;Wilson disease;Zinc;acute hepatitis/dt [Drug Therapy];acute hepatitis/pc [Prevention];animal experiment;animal model;animal tissue;article;chemical analysis;controlled study;correlation analysis;drug absorption;drug dose regimen;drug efficacy;drug liver level;drug tissue level;experimental design;feeding;iron metabolism;kidney;liver injury;male;nonhuman;rat;rat strain;stomach intubation;supplementation;symptomatology;8 hydroxydeoxyguanosine/cm [Drug Comparison];8 hydroxydeoxyguanosine/cr [Drug Concentration];8 hydroxydeoxyguanosine/dt [Drug Therapy];copper/cm [Drug Comparison];copper/cr [Drug Concentration];copper/dt [Drug Therapy];copper/pk [Pharmacokinetics];copper exporting adenosine triphosphatase/ec [Endogenous Compound];glucose/do [Drug Dose];glucose/dt [Drug Therapy];iron/cm [Drug Comparison];iron/cr [Drug Concentration];iron/dt [Drug Therapy];metallothionein/cm [Drug Comparison];metallothionein/cr [Drug Concentration];metallothionein/dt [Drug Therapy];zinc acetate/cm [Drug Comparison];zinc acetate/cr [Drug Concentration];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration];zinc acetate/pd [Pharmacology],"Medici, V.;Sturniolo, G. C.;Santon, A.;D'Inca, R.;Bortolami, M.;Cardin, R.;Basso, D.;Albergoni, V.;Irato, P.",2005,August,http://dx.doi.org/10.1111/j.1478-3231.2005.01108.x,0,0,
2174,Argyria: New physio-pathological and therapeutic hypothesis. [Italian],"The authors describe a case of sistemic argyria. They suggest a common physiopatologic mechanism with Wilson disease and they consider the utilization of penicillamine as a ligand for the silver, since there are not other available valid treatments.",Argyria;Ceruloplasmin;Colloidal silver;Cupper;Ligand;Penicillamine;Wilson disease;adult;argyria/dt [Drug Therapy];argyria/et [Etiology];article;case report;female;human;penicillamine/dt [Drug Therapy];silver,"Gunelli, M.;Barberini, M.;Bruni, S.;Laghi, L.;Mazzanti, A.;Fabbri, L.;Baldini, P. M.;Scaramucci, A.;Ragazzoni, R.;Muretto, P.;Maniscalco, G.",2005,March,,0,0,
2175,"Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric patients: A single-hospital, 10-year follow-up study","Wilson's disease (WD) is an inherited disorder of copper metabolism characterized by a failure of the liver to excrete copper, leading to its accumulation in the liver, brain, cornea, and kidney, with resulting chronic degenerative changes. It is generally accepted that ""presymptomatic"" patients--in whom WD is diagnosed in childhood and who are defined as those who, although still asymptomatic, do have liver disease, as indicated by increased serum concentrations of transaminases--should be treated prophylactically. Here we report our results in 22 children treated with continuous oral zinc therapy for 10 years. Zinc sulfate was administered at a dosage of 25 mg elemental zinc twice a day until the age of 6 years, 25 mg three times a day between the ages of 7 and 16 years or until the child attained a body weight of 125 lb, and 50 mg three times a day thereafter. Five years after the start of zinc treatment, we noted highly significant decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urinary copper excretion, but white blood cell counts did not vary significantly. Six of 22 patients continued to demonstrate greater-than-normal ALT concentrations and only 1 patient demonstrated an ALT concentration more than 1.5 times the upper normal limit. Further decreases in ALT, AST, and urinary copper excretion were observed at the end of the 10-year follow-up, but these decreases were not statistically significant. Only 1 patient continued to demonstrate abnormal ALT levels. Again, white blood cells showed no significant variations. All histologic scores (steatosis, inflammation, and fibrosis) were significantly decreased after treatment. Hepatic copper content was also significantly decreased, although it remained higher than normal in all patients. The removal of toxic copper was confirmed by disappearance of Kayser-Fleischer rings in 3 patients. Zinc did not have adverse effects on growth. The efficacy of zinc in WD in presymptomatic pediatric patients has been established in previous studies, and our study adds considerably to the earlier findings because it includes a large number of very young children, as many as 11 younger than 6 years and 20 younger than 10. The excellent clinical results in all patients, coupled with the improvement in hepatic histologic findings in the vast majority, indicate convincingly that zinc treatment can control the disease effectively and safely, preventing its progression over the course of 10 years. Histologic findings reportedly improved in 3 patients treated in an earlier study, but our data are numerically much more relevant. Notably, histologic study of the liver revealed that copper concentration was reduced by treatment, suggesting that oral zinc was able not only to prevent further accumulation of copper but also to promote, at least in part, the depletion of its stores. The lack of adverse effects of zinc on growth suggests that our patients received enough anticopper therapy to prevent damage resulting from copper toxicity but an adequate amount of copper for proper growth and development. In conclusion, our findings indicate that zinc is the treatment of choice in presymptomatic pediatric patients with WD. © 2005 Elsevier Inc. All rights reserved.",adolescent;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;bioaccumulation;blood cell count;body weight;child;clinical article;concentration response;controlled study;correlation analysis;disease course;dose response;drug dose regimen;drug efficacy;drug safety;enzyme assay;female;fibrosis;follow up;hemoconcentration;histology;human;inflammation;intermethod comparison;male;pediatrics;scoring system;side effect/si [Side Effect];statistical significance;steatosis;technique;toxicity/pc [Prevention];treatment outcome;urinary excretion;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Marcellini, M.;Di Ciommo, V.;Callea, F.;Devito, R.;Comparcola, D.;Sartorelli, M. R.;Carelli, F.;Nobili, V.",2005,March,http://dx.doi.org/10.1016/j.lab.2005.01.007,0,0,
2176,Rare genetically defined causes of dementia,"Several genetic disorders, though rare, are associated or present with dementia. Developments in the field of genetics are contributing to clarify and expand our knowledge of the complex physiopathological mechanisms leading to neurodegeneration and cognitive decline. Disorders associated with misfolded and aggregated proteins and lipid, metal or energy metabolism are examples of the multifarious disease processes converging in the clinical features of dementia, either as its predominant feature, as in cases of Alzheimer's disease (AD) or frontotemporal dementia (FTD), or as part of a cohort of accompanying or late-developing symptoms, as in Parkinson's disease (PD) or amyotrophic lateral sclerosis with dementia (ALS-D). Awareness of these disorders, allied with recent advances in genetic, biochemical and neuroimaging techniques, may lead to early diagnosis, successful treatment and better prognosis. © 2005 International Psychogeriatric Association.",Altered lipid metabolism;Altered metal metabolism;Dementia;Energy metabolism;Neurodegeneration;Protein aggregation disease;adrenoleukodystrophy/di [Diagnosis];adrenoleukodystrophy/dt [Drug Therapy];adrenoleukodystrophy/et [Etiology];adrenoleukodystrophy/th [Therapy];allogenic bone marrow transplantation;Alzheimer disease/di [Diagnosis];Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/di [Diagnosis];amyotrophic lateral sclerosis/et [Etiology];amyotrophic lateral sclerosis/th [Therapy];anxiety disorder/dt [Drug Therapy];autosomal dominant disorder/di [Diagnosis];autosomal dominant disorder/dt [Drug Therapy];autosomal dominant disorder/et [Etiology];cerebrotendinous xanthomatosis/di [Diagnosis];cerebrotendinous xanthomatosis/dt [Drug Therapy];cerebrotendinous xanthomatosis/et [Etiology];chelation;chorea/dt [Drug Therapy];clinical feature;cognitive defect;corticobasal degeneration/di [Diagnosis];corticobasal degeneration/et [Etiology];Creutzfeldt Jakob disease/di [Diagnosis];Creutzfeldt Jakob disease/et [Etiology];degenerative disease/di [Diagnosis];degenerative disease/et [Etiology];degenerative disease/th [Therapy];dementia/di [Diagnosis];dementia/et [Etiology];dentatorubropallidoluysian atrophy/di [Diagnosis];dentatorubropallidoluysian atrophy/et [Etiology];diagnostic procedure;differential diagnosis;diffuse Lewy body disease/di [Diagnosis];disease classification;familial british dementia/di [Diagnosis];familial british dementia/et [Etiology];familial british dementia/th [Therapy];familial disease/di [Diagnosis];familial disease/et [Etiology];familial encephalopathy with neuroserpin inclusion body/di [Diagnosis];familial encephalopathy with neuroserpin inclusion body/et [Etiology];fatal familial insomnia/di [Diagnosis];fatal familial insomnia/et [Etiology];frontotemporal dementia/di [Diagnosis];frontotemporal dementia/et [Etiology];frontotemporal dementia and parkinsonism linked to chromosome 17/di [Diagnosis];frontotemporal dementia and parkinsonism linked to chromosome 17/et [Etiology];gene function;gene mutation;gene replacement therapy;genetic association;genetic counseling;genetic disorder;Gerstmann Straussler Scheinker syndrome/di [Diagnosis];Gerstmann Straussler Scheinker syndrome/dt [Drug Therapy];Gerstmann Straussler Scheinker syndrome/et [Etiology];Hallervorden Spatz disease/di [Diagnosis];Hallervorden Spatz disease/et [Etiology];hepatocyte transplantation;human;Huntington chorea/di [Diagnosis];Huntington chorea/dt [Drug Therapy];Huntington chorea/et [Etiology];kufs disease/di [Diagnosis];kufs disease/dt [Drug Therapy];kufs disease/et [Etiology];lipid metabolism;metabolic disorder;metachromatic leukodystrophy/di [Diagnosis];metachromatic leukodystrophy/et [Etiology];metachromatic leukodystrophy/th [Therapy];metal metabolism;mitochondrial encephalomyopathy/di [Diagnosis];mitochondrial encephalomyopathy/et [Etiology];motor dysfunction/dt [Drug Therapy];myoclonus epilepsy/di [Diagnosis];myoclonus epilepsy/et [Etiology];nerve degeneration;neuroacanthocytosis/di [Diagnosis];neuroacanthocytosis/dt [Drug Therapy];neuroacanthocytosis/et [Etiology];neuroimaging;palliative therapy;Parkinson disease/di [Diagnosis];Parkinson disease/et [Etiology];parkinsonism/di [Diagnosis];parkinsonism/et [Etiology];pathophysiology;prognosis;progressive supranuclear palsy/di [Diagnosis];progressive supranuclear palsy/dt [Drug Therapy];progressive supranuclear palsy/et [Etiology];protein aggregation;protein folding;review;spinocerebellar degeneration/di [Diagnosis];spinocerebellar degeneration/et [Etiology];stem cell transplantation;tic/dt [Drug Therapy];treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];benzodiazepine/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];cholinergic receptor blocking agent/dt [Drug Therapy];cholinesterase inhibitor/dt [Drug Therapy];dopamine receptor stimulating agent/dt [Drug Therapy];Lorenzo oil/dt [Drug Therapy];methysergide/dt [Drug Therapy];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tau protein/ec [Endogenous Compound];tricyclic antidepressant agent/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc/dt [Drug Therapy];zonisamide/dt [Drug Therapy],"Novakovic, K. E.;Villemagne, V. L.;Rowe, C. C.;Masters, C. L.",2005,September,http://dx.doi.org/10.1017/S1041610205002012,0,0,
2177,Metabolic and endocrinological causes of dementia,"Deficiencies of vitamins B12, B3 and folate, abnormalities of cortisol metabolism, Wilson's disease, renal and hepatic failure, chronic obstructive pulmonary disease, hypo- and hypernatremia, thyroid and parathyroid dysfunction, hyper- and hypoglycemia and Marchiafava-Bignani disease are metabolic and endocrinological abnormalities that may be associated with cognitive impairment. In some cases these abnormalities may be causative of impaired cognition and in other situations merely associated with cognitive impairment. The existence of these conditions provides some justification for routine investigations commonly performed on patients presenting with possible early dementia. © 2005 International Psychogeriatric Association.",Cognitive impairment;Investigations;Tests;Thyroid disease;Vitamin deficiencies;Addison disease/dt [Drug Therapy];aged;aluminum overload;chronic obstructive lung disease/th [Therapy];cognitive defect;Cushing syndrome;cyanocobalamin deficiency;dementia/co [Complication];diabetes insipidus/dt [Drug Therapy];endocrine disease/dt [Drug Therapy];folic acid deficiency;hormone substitution;human;hypercalcemia/co [Complication];hypercortisolism;hyperglycemia;hypernatremia;hypoglycemia;hyponatremia;hypoparathyroidism;hypothalamus hypophysis system;hypothyroidism;inappropriate vasopressin secretion/dt [Drug Therapy];inappropriate vasopressin secretion/th [Therapy];kidney failure;liver failure/th [Therapy];Marchiafava Bignami disease;metabolic disorder/dt [Drug Therapy];nerve cell degeneration;nicotinic acid deficiency;oxygen therapy;parathyroid disease;pellagra/dt [Drug Therapy];review;vitamin deficiency;vitamin supplementation;Wilson disease/dt [Drug Therapy];corticosteroid/to [Drug Toxicity];corticotropin/to [Drug Toxicity];demeclocycline/dt [Drug Therapy];desmopressin/dt [Drug Therapy];desmopressin/na [Intranasal Drug Administration];glucocorticoid/dt [Drug Therapy];mineralocorticoid/dt [Drug Therapy];nicotinic acid/dt [Drug Therapy];nicotinic acid/po [Oral Drug Administration];prasterone/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Flicker, L.;Ames, D.",2005,September,http://dx.doi.org/10.1017/S1041610205001961,0,0,
2178,Wilson disease. [German],"Wilson disease is an autosomal recessive inherited disorder of human copper metabolism that leads to neurological symptoms and hepatic damage of variable degree. The affected gene ATP7B encodes a hepatic copper transport protein, which plays a key role in human copper metabolism. Clinical symptoms are complex with neurologic symptoms such as tremor, dysarthria, psychiatric disorders etc., predominant hepatic disease or mixed forms. Copper deposition in the liver results in acute liver failure, chronic hepatitis or liver cirrhosis. Early recognition by means of clinical, biochemical or genetic examination and early initiation of therapy with chelators or zinc-salts are essential for outcome and prognosis. Liver transplantation is an alternative in cases with acute and chronic liver failure and cures the hepatic disease. Frequent monitoring of drug therapy, adverse effects, and compliance is critical for the prognosis of the disease. © Springer Medizin Verlag 2005.",atp7b;Central nervous system;Copper;Liver toxicity;Wilson disease;aplastic anemia/si [Side Effect];article;autoimmune disease/si [Side Effect];autosomal recessive inheritance;chronic hepatitis;clinical trial;copper metabolism;diagnostic test;dysarthria;gene mutation;gene therapy;hepatocyte transplantation;human;liver cirrhosis;liver failure;liver injury;liver transplantation;mental disease;nephrotic syndrome/si [Side Effect];neurologic disease/si [Side Effect];pathogenesis;prognosis;symptomatology;toxicity;treatment outcome;tremor;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha tocopherol;antioxidant;carrier protein;chelating agent;histidine zinc/do [Drug Dose];histidine zinc/pd [Pharmacology];immunosuppressive agent;penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/do [Drug Dose];trientine/to [Drug Toxicity];trientine/pd [Pharmacology];unclassified drug;zinc acetate/do [Drug Dose];zinc acetate/pd [Pharmacology];zinc derivative/do [Drug Dose];zinc derivative/po [Oral Drug Administration];zinc derivative/pd [Pharmacology];zinc sulfate/do [Drug Dose];zinc sulfate/pd [Pharmacology],"Huster, D.;Kuhn, H. J.;Mossner, J.;Caca, K.",2005,July,http://dx.doi.org/10.1007/s00108-005-1432-7,0,0,
2179,Severe autonomic dysfunction as a presenting feature of Wilson's disease [4],,adult;anamnesis;autonomic dysfunction/dt [Drug Therapy];case report;clinical feature;disease severity;human;laboratory test;letter;male;stomach paresis/di [Diagnosis];Wilson disease/dt [Drug Therapy];fludrocortisone/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Kumar, S.",2005,January/March,,0,0,
2180,Erratum: Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric patients: A single-hospital 10-year follow-up study (Journal of Laboratory and Clinical Medicine (2005) 145 (139-143) PII: S0022214305000089),,erratum;error,"Marcellini, M.;Di Ciommo, V.;Callea, F.;Devito, R.;Comparcola, D.;Sartorelli, M. R.",2005,01 Jul,http://dx.doi.org/10.1016/j.lab.2005.06.008,0,0,
2181,Adopting an orphan,,acromegaly/dt [Drug Therapy];adenomatous polyp/dt [Drug Therapy];adrenal cortex carcinoma/dt [Drug Therapy];article;chronic myeloid leukemia/dt [Drug Therapy];chronic pain/dt [Drug Therapy];commercial phenomena;drug approval;drug industry;drug marketing;drug research;dysplasia/dt [Drug Therapy];economic aspect;enzyme deficiency/dt [Drug Therapy];Fabry disease/dt [Drug Therapy];financial management;Gaucher disease/dt [Drug Therapy];human;Hurler syndrome/dt [Drug Therapy];legal aspect;nonhodgkin lymphoma/dt [Drug Therapy];patent ductus arteriosus/dt [Drug Therapy];priority journal;promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];thrombocythemia/dt [Drug Therapy];tyrosinemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase beta/dt [Drug Therapy];anagrelide/dt [Drug Therapy];arsenic trioxide/dt [Drug Therapy];bosentan/dt [Drug Therapy];busulfan/dt [Drug Therapy];busulfan/iv [Intravenous Drug Administration];carglumic acid;celecoxib/dt [Drug Therapy];cladribine/dt [Drug Therapy];cladribine/sc [Subcutaneous Drug Administration];glutamate acetyltransferase/ec [Endogenous Compound];glutamic acid derivative/dt [Drug Therapy];ibuprofen/dt [Drug Therapy];iloprost/dt [Drug Therapy];imatinib/dt [Drug Therapy];laronidase/dt [Drug Therapy];litak;miglustat/dt [Drug Therapy];mitotane/dt [Drug Therapy];n carbamylglutamic acid/dt [Drug Therapy];nitisinone/dt [Drug Therapy];omega conotoxin MVIIA/dt [Drug Therapy];omega conotoxin MVIIA/sp [Intraspinal Drug Administration];pegvisomant/dt [Drug Therapy];photofrin/dt [Drug Therapy];unclassified drug;wilzin;zinc acetate/dt [Drug Therapy],"Rinaldi, A.",2005,June,http://dx.doi.org/10.1038/sj.embor.7400450,0,0,
2182,Wilson's disease: Clinical management and therapy,"This review focuses on the treatment and management of patients with Wilson's disease. A central feature of management is choice of anticopper drug or drugs for various stages and classes of disease. Physicians should no longer rely on penicillamine as their major choice for treating this disease. In fact, our recommendation is that penicillamine be rarely used. For initial treatment of the hepatic failure presentation, we recommend a combination of trientine and zinc. For initial treatment of the neurologic/psychiatric presentation, we recommend tetrathiomolybdate and zinc. If tetrathiomolybdate is not available our second choice is zinc alone. For maintenance therapy (usually 2--4 months after initial therapy), for presymptomatic patients, and for pregnant patients, zinc is recommended with trientine as second choice. Monitoring recommendations for both efficacy and safety for these various anticopper drugs are provided. Hepatic transplantation should be reserved for only patients with severe liver failure, and never used for neurologic indications. Information on how to triage liver failure patients is provided. Other aspects of management, including diet, drinking water, physical therapy, and concomitant medical therapy, as well as prognosis and long term risks are also discussed. © 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",anemia/si [Side Effect];bone marrow suppression/si [Side Effect];chelation therapy;copper deficiency/co [Complication];copper metabolism;disease exacerbation/si [Side Effect];drug cytotoxicity/si [Side Effect];drug hypersensitivity/si [Side Effect];gastrointestinal toxicity/si [Side Effect];general condition deterioration;Goodpasture syndrome/si [Side Effect];hepatic encephalopathy/co [Complication];hepatitis A/dt [Drug Therapy];hepatitis A/pc [Prevention];hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];human;infection prevention;infection risk;leukopenia/si [Side Effect];liver failure/co [Complication];liver graft;neurotoxicity/si [Side Effect];patient compliance;patient monitoring;portal hypertension/co [Complication];practice guideline;priority journal;prognosis;proteinuria/si [Side Effect];pyridoxine deficiency/dt [Drug Therapy];review;systemic lupus erythematosus/si [Side Effect];urinary excretion;Wilson disease/dt [Drug Therapy];wrinkle;copper;gluconate zinc/ae [Adverse Drug Reaction];gluconate zinc/cb [Drug Combination];gluconate zinc/dt [Drug Therapy];hepatitis A vaccine/dt [Drug Therapy];hepatitis B vaccine/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc acetate;zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Brewer, G. J.;Askari, F. K.",2005,April,http://dx.doi.org/10.1016/j.jhep.2004.11.013,0,0,
2183,Acute liver failure,"Acute liver failure is a complex multisystemic illness that evolves quickly after a catastrophic insult to the liver leading to the development of encephalopathy. The underlying aetiology and the pace of progression strongly influence the clinical course. The commonest causes are paracetamol, idiosyncratic drug reactions, hepatitis B, and seronegative hepatitis. The optimal care is multidisciplinary and up to half of the cases receive liver transplants, with survival rates around 75%-90%. Artificial liver support devices remain unproven in efficacy in acute liver failure.","Amanita phalloides;artificial liver;autoimmune hepatitis;blood clotting disorder;brain disease/co [Complication];brain edema;Budd Chiari syndrome;disease association;disease course;drug overdose;enteric feeding;hepatitis A;hepatitis B;human;hypoglycemia;hypokalemia;hyponatremia;hypotension;intoxication;liver failure/di [Diagnosis];liver failure/dt [Drug Therapy];liver failure/et [Etiology];liver failure/su [Surgery];liver failure/th [Therapy];liver function test;liver transplantation;metabolic alkalosis;primary medical care;prognosis;prothrombin time;rehydration;respiratory failure;resuscitation;review;sepsis;seronegative hepatitis;survival rate;Wilson disease;3,4 methylenedioxymethamphetamine;acetylcysteine/dt [Drug Therapy];acetylcysteine/iv [Intravenous Drug Administration];allopurinol;amiodarone;benoxaprofen;carbamazepine;didanosine;disulfiram;enflurane;flutamide;gold;halothane;immunosuppressive agent/dt [Drug Therapy];isoflurane;isoniazid;ketoconazole;lamivudine/dt [Drug Therapy];methyldopa;monoamine oxidase inhibitor;nonsteroid antiinflammatory agent;paracetamol;penicillamine/dt [Drug Therapy];phenytoin;propylthiouracil;rifampicin;sulfonamide;tetracycline;tricyclic antidepressant agent;valproic acid","O'Grady, J. G.",2005,March,http://dx.doi.org/10.1136/pgmj.2004.026005,0,0,
2184,Wilson's disease: Clinical presentations. [French],"Wilson's disease is a rare genetic condition, transmitted on a recessive autosomal mode, which involves a disturbance of copper metabolism. Its prevalence is 1:30 000. It is treatable but may be lethal if not managed early and treated adequately. It is caused by the loss of function of an adenosine triphosphatase (ATP 7B), which is due to a mutation in the ATP 7B gene on chromosome 13. This leads to a decrease or absence of copper transport to the bile and its accumulation within certain organs, particularly the liver and the brain. In this article we present two cases of Wilson's disease in two young male patients. We also briefly review the pathophysiology of the illness, discuss the latest guidelines for diagnosis and treatment and outline the recent genetic discoveries.",anamnesis;autosomal recessive disorder;biopsy;case report;chromosome 13;clinical feature;copper metabolism;echography;enzyme defect;gene mutation;genetic disorder;human;liver cirrhosis;male;neurologic disease;prevalence;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Chilcott-Lauber, C.;Burkhard, P. R.;Giostra, E.",2005,07 Sep,,0,0,
2185,Cannabis sativa and dystonia secondary to Wilson's disease,A patient with generalized dystonia due to Wilson's disease obtained marked improvement in response to smoking cannabis. © 2004 Movement Disorder Society.,Cannabis;Dystonia;Wilson's disease;adult;anxiety;article;bradykinesia;case report;depression/dt [Drug Therapy];disease exacerbation;drug response;drug withdrawal;dysarthria;dysphagia;dystonia/dt [Drug Therapy];follow up;gait disorder;human;hypersalivation;insomnia;irritability;male;muscle rigidity;priority journal;sedation;side effect/si [Side Effect];smoking;suicide attempt;tremor;walking;Wilson disease/dt [Drug Therapy];xerostomia/si [Side Effect];cannabis/ae [Adverse Drug Reaction];cannabis/dt [Drug Therapy];clonazepam/cb [Drug Combination];clonazepam/dt [Drug Therapy];diazepam/dt [Drug Therapy];paroxetine/cb [Drug Combination];paroxetine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy],"Uribe Roca, M. C.;Micheli, F.;Viotti, R.",2005,January,http://dx.doi.org/10.1002/mds.20268,0,0,
2186,Wilson's disease with depression and parkinsonism,"Wilson's disease (WD) is an autosomal recessive disorder with reduced biliary excretion of copper plus impaired formation of ceruloplasmin, leading to copper accumulation in the liver, brain, kidney, and cornea. Clinical manifestations include liver damage, psychiatric symptoms, and neurological features. We report a 35-year-old woman with a history of deranged liver functions who had severe depression several years later and eventually presented with parkinsonian features. The underlying diagnosis is WD and family screening revealed WD in 2 other siblings. She could not tolerate penicillamine because of fever and leucopenia. While taking trientine hydrochloride and zinc sulphate, her parkinsonism improved and her depression remained in remission. WD should be considered in patients with unexplained liver function derangement or psychiatric symptoms. Early diagnosis and initiation of specific treatment are crucial in minimising any further cerebral and hepatic damage as well as securing possible improvement in organ functions. © 2004 Published by Elsevier Ltd.",Depression;Parkinsonism;Penicillamine;Trientine hydrochloride;Wilson's disease;adult;anamnesis;article;brain injury;case report;depression/dt [Drug Therapy];depression/th [Therapy];disease severity;drug fever/si [Side Effect];drug tolerability;family;female;human;leukopenia/si [Side Effect];liver function;liver injury;mental disease;parkinsonism/dt [Drug Therapy];priority journal;remission;screening test;sibling;Wilson disease/dt [Drug Therapy];haloperidol/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];serotonin uptake inhibitor/dt [Drug Therapy];trientine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Chan, K. H.;Cheung, R. T. F.;Au-Yeung, K. M.;Mak, W.;Cheng, T. S.;Ho, S. L.",2005,April,http://dx.doi.org/10.1016/j.jocn.2004.09.005,0,0,
2187,The latest orphan drug designations and the Commission Communication on Regulation (EC) 141/2000,"The implementation of Community Regulation on orphan medicinal products in the European Union in April 2000 has resulted in a deluge of applications for designation of medicinal products as orphan for rare diseases. By April 2004, the Committee for Orphan Medicinal Products had already given positive opinion on 63 per cent of the 316 applications considered by them. A significant number of these positive designations have already matured into full marketing authorisations. Three major reasons - failure to meet prevalence or significant benefit criteria or provide evidence of biological plausibility - have equally contributed to either the negative opinion on or the applicants withdrawing the remaining applications. In July 2004, the European Commission issued a communication setting out its position on certain matters relating to the implementation of the designation and market exclusivity provisions. The Commission, the European Medicines Agency (EMEA) and the Committee for Orphan Medicinal Products (COMP) continue to be proactive and provide as much guidance and incentives as practical, engaging themselves with sponsors, patient groups and academia. As experience builds up and issues are clarified, there are expectations that the Community Regulation on orphan medicines will prove to be a spectacular success. © Henry Stewart Publications.",Biological plausibility;Commission communication;Orphan medicinal products;Prevalence;Protocol assistance;Significant benefit;acromegaly/dt [Drug Therapy];adenomatous polyp/dt [Drug Therapy];adrenal cortex carcinoma/dt [Drug Therapy];article;Barrett esophagus/dt [Drug Therapy];chronic myeloid leukemia/dt [Drug Therapy];chronic pain/dt [Drug Therapy];clinical protocol;drug approval;drug industry;drug marketing;European Union;experience;Fabry disease/dt [Drug Therapy];Gaucher disease/dt [Drug Therapy];hairy cell leukemia/dt [Drug Therapy];health care organization;hematopoietic stem cell transplantation;human;hyperammonemia/dt [Drug Therapy];medicolegal aspect;mucopolysaccharidosis/dt [Drug Therapy];patent ductus arteriosus/dt [Drug Therapy];practice guideline;promyelocytic leukemia/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];thrombocythemia/dt [Drug Therapy];tyrosinemia/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];agalsidase alfa/iv [Intravenous Drug Administration];agalsidase beta/dt [Drug Therapy];agalsidase beta/iv [Intravenous Drug Administration];anagrelide/dt [Drug Therapy];anagrelide/po [Oral Drug Administration];arsenic trioxide/dt [Drug Therapy];arsenic trioxide/iv [Intravenous Drug Administration];bosentan/dt [Drug Therapy];bosentan/po [Oral Drug Administration];busulfan;carglumic acid/dt [Drug Therapy];carglumic acid/po [Oral Drug Administration];celecoxib/dt [Drug Therapy];celecoxib/po [Oral Drug Administration];cladribine/dt [Drug Therapy];cladribine/sc [Subcutaneous Drug Administration];DNA/dt [Drug Therapy];ibuprofen/dt [Drug Therapy];ibuprofen/iv [Intravenous Drug Administration];iloprost/dt [Drug Therapy];iloprost/ih [Inhalational Drug Administration];imatinib/dt [Drug Therapy];imatinib/po [Oral Drug Administration];immunomodulating agent/dt [Drug Therapy];laronidase/dt [Drug Therapy];laronidase/iv [Intravenous Drug Administration];litak;miglustat/dt [Drug Therapy];miglustat/po [Oral Drug Administration];mitotane/dt [Drug Therapy];mitotane/po [Oral Drug Administration];monoclonal antibody/dt [Drug Therapy];new drug/dt [Drug Therapy];new drug/po [Oral Drug Administration];nitisinone/dt [Drug Therapy];omega conotoxin MVIIA/dt [Drug Therapy];orphan drug/dt [Drug Therapy];orphan drug/ih [Inhalational Drug Administration];orphan drug/iv [Intravenous Drug Administration];orphan drug/po [Oral Drug Administration];orphan drug/sc [Subcutaneous Drug Administration];pegvisomant/dt [Drug Therapy];pegvisomant/sc [Subcutaneous Drug Administration];photofrin/dt [Drug Therapy];photofrin/iv [Intravenous Drug Administration];unclassified drug;wilzin;xagird;zinc acetate/dt [Drug Therapy],"Shah, R. R.",2005,April,http://dx.doi.org/10.1057/palgrave.jcb.3040122,0,0,
2188,Serum transaminases in children with Wilson's disease,"OBJECTIVES: The response of serum transaminase levels to penicillamine and zinc treatment in Wilson's disease is poorly understood. The aim of this multicenter retrospective study was to evaluate transaminase levels after penicillamine and zinc treatment in children with Wilson's disease. PATIENTS AND METHODS: One hundred and nine patients with Wilson's disease (median age at diagnosis, 7.2 years; range, 1 to 18 years), treated for at least 12 months and observed in the last 20 years at 11 Paediatric Departments were studied. Clinical, laboratory and histologic features at diagnosis and initial treatment were recorded. Efficacy parameters were normalization of serum transaminase level and improved clinical and/or laboratory signs. One hundred and two patients had clinical or laboratory signs of liver disease. RESULTS: Fifty-six of 87 patients (64%) given penicillamine normalized serum alanine aminotransferase (ALT) levels within a median of 17 months (range, 2 to 96 months). Of the 29 patients with persistent hyper-ALT, 17 (59%) switched to zinc; only four of these normalized ALT on zinc within a median period of 38 months (range, 7 to 48 months). Eleven (50%) of the 22 patients given zinc alone normalized ALT within a median period of 6 months (range, 1 to 36 months). Of the 11 patients with persistent hyper-ALT, five switched to penicillamine. Three of the five normalized ALT within a median period of 6 months (range, 6 to 9 months). Overall, in penicillamine-treated and zinc-treated patients with persistent hypertransaminasemia, ALT decreased from a basal median of 236 IU/L (range, 54 to 640 IU/L) to a median of 78 (range, 46 to 960 IU/L) at the end of follow-up (P = 0.0245). Poor compliance was suspected in only 10% of cases. No predictive factor of persistent hypertransaminasemia was identified. Liver disease did not worsen in any patient during the study. CONCLUSIONS: Although the efficacy of penicillamine and zinc is well documented, it is notable that a subset of children with Wilson's disease-related liver disease (36%) had hypertransaminasemia despite appropriate treatment with penicillamine or zinc.",adolescent;article;blood;child;comparative study;enzymology;female;human;infant;liver;male;pathology;preschool child;retrospective study;Wilson disease/dt [Drug Therapy];alanine aminotransferase;penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Iorio, R.;D'Ambrosi, M.;Marcellini, M.;Barbera, C.;Maggiore, G.;Zancan, L.;Giacchino, R.;Vajro, P.;Marazzi, M. G.;Francavilla, R.;Michielutti, F.;Resti, M.;Frediani, T.;Pastore, M.;Mazzarella, G.;Fusco, G.;Cirillo, F.;Vegnente, A.",2004,Oct,,1,1,
2189,Diagnostics considerations in juvenile parkinsonism,"Juvenile parkinsonism (JP) describes patients in whom the clinical features of parkinsonism manifest before 21 years of age. Many reported cases that had a good response to levodopa have proved to have autosomal recessive juvenile parkinsonism (AR-JP) due to mutations in the parkin gene. With the exception of parkin mutations and dopa-responsive dystonia, most causes are associated with the presence of additional neurological signs, resulting from additional lesions outside of the basal ganglia. Lewy body pathology has only been reported in one case, suggesting that a juvenile form of idiopathic Parkinson's disease may be extremely rare. © 2003 Movement Disorder Society.",Juvenile parkinsonism;Parkin;acanthocytosis;adolescent;adolescent disease/di [Diagnosis];adolescent disease/dt [Drug Therapy];adolescent disease/et [Etiology];adolescent disease/si [Side Effect];akathisia/si [Side Effect];autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];basal ganglion;bone marrow transplantation;bradykinesia/si [Side Effect];brain injury;cell nucleus inclusion body;central pontine myelinolysis;clinical feature;diagnostic test;diffuse Lewy body disease;drug induced disease/si [Side Effect];drug response;dystonia/dt [Drug Therapy];dystonia/si [Side Effect];epidemic encephalitis;gene mutation;genetic disorder;human;Human immunodeficiency virus infection/dt [Drug Therapy];Huntington chorea;hypotension;hypoxia;idiopathic disease/di [Diagnosis];idiopathic disease/dt [Drug Therapy];intoxication;lung aspergillosis/dt [Drug Therapy];metabolic disorder;mitochondrion;Mycoplasma pneumonia;neurologic disease;neuropathology;parkinsonism/di [Diagnosis];parkinsonism/dt [Drug Therapy];parkinsonism/et [Etiology];parkinsonism/si [Side Effect];positron emission tomography;priority journal;review;single photon emission computer tomography;spinocerebellar degeneration;subacute sclerosing panencephalitis/dt [Drug Therapy];subacute sclerosing panencephalitis/pc [Prevention];systemic lupus erythematosus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];6 fluorodopa;amlodipine/ae [Adverse Drug Reaction];amphotericin B/dt [Drug Therapy];antiretrovirus agent/ae [Adverse Drug Reaction];antiretrovirus agent/dt [Drug Therapy];chloroquine/ae [Adverse Drug Reaction];cinnarizine/ae [Adverse Drug Reaction];dimercaprol/dt [Drug Therapy];dopamine/ec [Endogenous Compound];doxorubicin/ae [Adverse Drug Reaction];flunarizine/ae [Adverse Drug Reaction];iodine 123;levodopa/ae [Adverse Drug Reaction];levodopa/dt [Drug Therapy];measles vaccine/dt [Drug Therapy];metoclopramide/ae [Adverse Drug Reaction];n [(1 ethyl 2 pyrrolidinyl)methyl] 3 iodo 6 methoxysalicylamide;neuroleptic agent/ae [Adverse Drug Reaction];nifedipine/ae [Adverse Drug Reaction];oral contraceptive agent/po [Oral Drug Administration];parkin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phenylalanine;prochlorperazine/ae [Adverse Drug Reaction];tetrahydrobiopterin/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];tyrosine 3 monooxygenase/ec [Endogenous Compound];unindexed drug;valproic acid/ae [Adverse Drug Reaction];vincristine/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Paviour, D. C.;Surtees, R. A. H.;Lees, A. J.",2004,,http://dx.doi.org/10.1002/mds.10644,0,0,
2190,"Cavernous transformation of the portal vein causing jaundice, presenting in the form of Wilson's disease","The following is a case review of portal vein cavernous malformation presenting with intermittent cholestasis and jaundice in a 4 year old child. Correct assessment was supported by radiology, later laparoscopy, yet hindered by histopathology representative Wilson's disease and elevated urinary copper excretion. During surgical procedure the stenosis of the common bile duct secondary to extremely dilated portal vein reticulation was solved by Roux-en-Y choledochojejunostomy. After a one-year follow up the child remains asymptomatic.",Cholestasis;Portal vein cavernoma;Wilson's disease;anamnesis;case report;child;choledochojejunostomy;chronic hepatitis/di [Diagnosis];clinical feature;female;follow up;human;jaundice/di [Diagnosis];laboratory diagnosis;laboratory test;laparoscopy;physical examination;portal vein;review;stenosis;surgical technique;vein malformation/di [Diagnosis];vein malformation/su [Surgery];Wilson disease/di [Diagnosis];copper/ec [Endogenous Compound];penicillamine,"Ruszinko, V.;Kovacs, M.;Szonyi, L.;Verebely, T.;Willner, P.",2004,August,,0,0,
2191,Wilson disease. [Japanese],,chromosome 13;dementia/et [Etiology];diagnostic procedure;differential diagnosis;genetics;human;liver transplantation;mutation;onset age;review;Wilson disease/di [Diagnosis];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/th [Therapy];adenosine triphosphatase;biological marker/an [Drug Analysis];cation transport protein;ceruloplasmin/an [Drug Analysis];chelating agent/dt [Drug Therapy];copper/an [Drug Analysis];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein;zinc/dt [Drug Therapy],"Shimizu, N.",2004,Jan,,0,0,
2192,Fibrosing alveolitis as a complication due to D-penicillamine therapy for Wilson-Konovalov disease. [Russian],,adult;article;case report;chemically induced disorder;human;lung fibrosis;male;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy],"Rakhimova, O. I.;Rozina, T. P.;Popova, E. N.;Lopatkina, T. N.;Ignatova, T. M.",2004,,,0,0,
2193,Effects of high level Zn intake on metabolism in man. [Chinese],"OBJECTIVE: To observe the effects of high level Zn intake on zinc (Zn) copper (Cu), lipids metabolism and antioxidation function in man so as to provide scientific basis for Zn supplementation. METHODS: 40 rural healthy men were chosen and tablets of 50 mg Zn (as 0.2 g of zinc glucose) per day was taken by them for eight weeks. All subjects were checked up for five times: at week 0, 2, 4, 8 during the period of Zn supplementation and at week 12 and their serum, RBC, hair, and 24h-urine were collected for assays at the same time. RESULTS: (1) Zn contents in serum, RBC and hair increased significantly after 2 to 4 weeks supplementation and decreased at 4 weeks after stopping supplementation, but they were still higher than those before supplementation. Zn contents in 24h-urine increased significantly after supplementation and decreased at 4 weeks after stopping supplementation to the same level as before supplementation. (2) Cu contents in serum, RBC and hair increased significantly after 4 weeks supplementation and decreased at 4 weeks after stopping supplementation. Cu contents in 24h-urine did not change significantly during experiment. (3) RBC superoxide dismutase (SOD) activities were decreased persistently after 2 weeks supplementation and were not recovered at 4 weeks after stopping supplementation. RBC glutathione peroxidase (GPX) activities increased significantly after 4 weeks supplementation. The content of lipid peroxide (LPO) increased significantly after 2 weeks supplementation. (4) Total cholesterol (TC), triglyceride (TG), Low density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (ApoB100) increased significantly, high density lipoprotein cholesterol (HLD-C) and apolipoprotein A1 (ApoA1) decreased after supplementation. CONCLUSION: When healthy men received 50 mg Zn supplement per day, it might interfere Zn, Cu and lipids metabolism and inhibit antioxidation process.",adolescent;adult;article;blood;diet supplementation;drug effect;female;human;lipid peroxidation;male;metabolism;rural population;antioxidant/ad [Drug Administration];copper;glutathione peroxidase;lipid;lipid peroxide;superoxide dismutase;zinc/ad [Drug Administration],"Xiang, Y.;Yang, X.;Bian, J.;Wang, L.",2004,Nov,,0,0,
2194,Neurodegenerative diseases and oxidatives stress,"Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Oxygen is vital for life but is also potentially dangerous, and a complex system of checks and balances exists for utilizing this essential element. Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. The systems in place to cope with the biochemistry of oxygen are complex, and many questions about the mechanisms of oxygen regulation remain unanswered. However, this same complexity provides a number of therapeutic targets, and different strategies, including novel metal-protein attenuating compounds, aimed at a variety of targets have shown promise in clinical studies.",Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/dt [Drug Therapy];amyotrophic lateral sclerosis/et [Etiology];blood brain barrier;cell killing;cell loss;cerebrospinal fluid;clinical trial;degenerative disease/dt [Drug Therapy];degenerative disease/et [Etiology];disease course;drug mechanism;drug penetration;enzyme activity;Friedreich ataxia/et [Etiology];homeostasis;human;nerve cell;oxidative stress;Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];priority journal;regulatory mechanism;review;risk factor;Wilson disease/dt [Drug Therapy];alpha tocopherol/ct [Clinical Trial];alpha tocopherol/dt [Drug Therapy];alpha tocopherol/pd [Pharmacology];amantadine/ct [Clinical Trial];amantadine/dt [Drug Therapy];amantadine/pd [Pharmacology];amyloid precursor protein/ec [Endogenous Compound];antioxidant/ct [Clinical Trial];antioxidant/dt [Drug Therapy];antioxidant/pk [Pharmacokinetics];antioxidant/pd [Pharmacology];catalase/ec [Endogenous Compound];clioquinol/ct [Clinical Trial];clioquinol/dt [Drug Therapy];clioquinol/po [Oral Drug Administration];clioquinol/pd [Pharmacology];copper;deferoxamine/ct [Clinical Trial];deferoxamine/dt [Drug Therapy];deferoxamine/im [Intramuscular Drug Administration];deferoxamine/pd [Pharmacology];dopamine/ec [Endogenous Compound];glutathione peroxidase/ec [Endogenous Compound];glutathione reductase/ec [Endogenous Compound];memantine/dt [Drug Therapy];memantine/pd [Pharmacology];neurotrophin/dt [Drug Therapy];neurotrophin/pk [Pharmacokinetics];neurotrophin/pd [Pharmacology];oxygen;reactive oxygen metabolite;riluzole/dt [Drug Therapy];riluzole/pd [Pharmacology];superoxide dismutase/ec [Endogenous Compound];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics];trientine/pd [Pharmacology],"Barnham, K. J.;Masters, C. L.;Bush, A. I.",2004,March,,0,0,
2195,Wilson's disease and secondary copper hemochromatoses in hematological practice. [Russian],"AIM: To characterize clinical, diagnostic and therapeutic syndromes of copper overloading in patients with hepatic lesion in combination with hemopoietic disorder. MATERIAL AND METHODS: Treatment results and diagnostic findings are presented for patients with clinical picture of liver cirrhosis, cytopenia and copper overloading. The examination included standard clinical and specific tests, morphological investigation of the bone marrow, copper metabolism in dynamics. RESULTS: A case of a patient is reported in whom Wilson's disease presented in debut with a picture of decompensated liver cirrhosis and immune thrombocytopania complicated by recurrent hemorrhagic syndrome. D-penicillomine treatment initiated ex juvantibus allowed verification of the diagnosis of Wilson's disease and achievement of marked clinical response. In another case laboratory signs of copper overloading were revealed in a patient with liver cirrhosis of viral etiology (HBsAg+) and deep cytopenia associated with uneffective hemopoiesis. Chelator therapy with D-penicillamine regressed cytopenic syndrome and improved functional capacity of the liver. CONCLUSION: Primary or secondary nature of copper overloading in patients with hepatic cirrhosis and critical cytopenia, pathogenesis of cytopenic syndrome, practical significance of copper hemochromatoses diagnosis are discussed.",adult;article;blood;case report;differential diagnosis;drug administration;hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];human;liver cirrhosis/di [Diagnosis];male;metabolism;treatment outcome;urine;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/ad [Drug Administration];chelating agent/dt [Drug Therapy];copper;penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Vorob'ev, A. I.;Lukina, E. A.;Sysoeva, E. P.;Levina, A. A.;Solov'eva, T. I.",2004,,,0,0,
2196,Wilson's disease and its pharmacological treatment. [Japanese],"Wilson's disease is an inherited copper toxicosis caused by defective putative copper transporting ATPase in the liver. Because of impaired biliary secretion, copper remains in the liver, resulting in chronic hepatic lesions including fatty metamorphosis, chronic hepatitis and cirrhosis. In the latter stage, extrapyramidal syndromes may develop with and without symptomatic hepatic lesions. Acute liver damage associated with hemolysis and deep jaundice may be the first manifestation. The majority of patients show hypoceruloplasminemia, which has been used as a screening test for the disease. A large number of mutations in the ATP7B gene have been reported. Thus, genetic diagnosis might be limitedly used to presymptomatic diagnosis of siblings when mutations are identified in an index patient. Introduction of penicillamine caused a revolution in the treatment of patients. Another chelater, trientine, is now available for those intolerant of penicillamine. Tetrathiomolibdate and zinc acetate are additional alternatives currently being tested. Hypoceruloplasminemia and further reduction after chelation therapy may be associated with iron overload. This complication is closely related with impaired transport of ferrous ion due to ferroxidase deficiency. Noncompliance and teratogenicity are other major concerns because any treatment with the agents listed above is a life long regimen. Despite various side effects of penicillamine, its teratogenicity is negligible. These data indicate that penicillamine is the first choice of drug for this disease. © 2004 The Pharmaceutical Society of Japan.",atp7b;Copper chelation;Iron accumulation;chelation;clinical feature;disease course;gene mutation;genetic analysis;human;iron overload/co [Complication];laboratory test;pathophysiology;review;teratogenicity;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein;zinc acetate/dt [Drug Therapy],"Hayashi, H.;Suzuki, R.;Wakusawa, S.",2004,November,http://dx.doi.org/10.1248/yakushi.124.711,0,0,
2197,Wilson's disease and hemochromatosis,"Wilson's disease (WD) and hereditary hemochromatosis (HH) are two inherited disorders with potentially devastating and life-threatening complications. Their eminent treatability makes diagnosis in adolescence or young adulthood critical. WD is the result of abnormal copper homeostasis, causing copper overload and end-organ damage. Chelation therapy can be highly efficacious in preventing manifestations of WD. HH is caused by inappropriate absorption of dietary iron, typically as the result of a specific mutation, C282Y, in the HFE gene. End-organ disease from iron accumulation is protean and includes progressive damage of the liver, pancreas, skin, heart, and pituitary. It is important to permit therapeutic phlebotomy to commence before the onset of complications.",adolescent;bone marrow suppression/si [Side Effect];clinical feature;copper metabolism;diagnostic procedure;drug effect;drug hypersensitivity/si [Side Effect];drug mechanism;gastrointestinal symptom/si [Side Effect];gene mutation;genetic risk;health survey;hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/ep [Epidemiology];hemochromatosis/su [Surgery];homeostasis;human;laboratory test;liver transplantation;lupus erythematosus/si [Side Effect];medical examination;nephrosis/si [Side Effect];pathophysiology;review;side effect/si [Side Effect];skin toxicity/si [Side Effect];treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/su [Surgery];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];tetrathiomolybdenate/ae [Adverse Drug Reaction];tetrathiomolybdenate/dt [Drug Therapy];tetrathiomolybdenate/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];unclassified drug;zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Neimark, E.;Schilsky, M. L.;Shneider, B. L.",2004,February,http://dx.doi.org/10.1016/j.admecli.2003.11.011,0,0,
2198,Wilson's disease with coexisting autoimmune hepatitis [2],,adult;aged;anamnesis;antibiotic therapy;autoimmune hemolytic anemia/di [Diagnosis];autoimmune hemolytic anemia/dt [Drug Therapy];autoimmune hepatitis/dt [Drug Therapy];autopsy;bacterial endocarditis/di [Diagnosis];bacterial endocarditis/dt [Drug Therapy];cause of death;clinical feature;comorbidity;disease course;disease severity;female;hepatic encephalopathy/di [Diagnosis];hepatic encephalopathy/dt [Drug Therapy];hospital admission;human;laboratory test;length of stay;letter;liver failure/di [Diagnosis];liver failure/dt [Drug Therapy];liver failure/su [Surgery];liver function test;liver transplantation;neurologic examination;priority journal;septic shock/di [Diagnosis];septic shock/dt [Drug Therapy];treatment indication;treatment outcome;Wilson disease/dt [Drug Therapy];azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];gentamicin/cb [Drug Combination];gentamicin/dt [Drug Therapy];methylprednisolone/cb [Drug Combination];methylprednisolone/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];prednisolone/cb [Drug Combination];prednisolone/dt [Drug Therapy];sultamicillin/cb [Drug Combination];sultamicillin/dt [Drug Therapy],"Yener, S.;Akarsu, M.;Karacanci, C.;Sengul, B.;Topalak, O.;Biberoglu, K.;Akpinar, H.",2004,January,http://dx.doi.org/10.1111/j.1440-1746.2004.03254.x,0,0,
2199,Metabolic liver disease in the young adult,"This chapter describes the gene mutations, phenotypes, diagnosis and therapy of the common metabolic liver diseases in young adulthood: haemochromatosis, Wilson disease, alpha<inf>1</inf>-anti-trypsin deficiency and cystic fibrosis. The remarkable variability of the phenotypical expression of the mutated genotypes makes screening recommendations and the establishment of prognosis for these liver disorders in young adults problematical. The diagnosis and therapy of the young adult with metabolic liver disease is discussed, with an emphasis on maintaining quality-of-life and balancing the importance of early intervention with the stigmatization of the diagnosis of potentially life-threatening liver disease. There is a critical need for the development of biochemical markers that would predict the risk of expression of clinical phenotypes and prognosis. © 2003 Elsevier Science Ltd. All rights reserved.",alpha<inf>1</inf>anti- trypsin;Cystic fibrosis;Haemochromatosis;Liver disease;Wilson disease;alpha 1 antitrypsin deficiency/su [Surgery];clinical feature;cystic fibrosis/di [Diagnosis];cystic fibrosis/dt [Drug Therapy];cystic fibrosis/su [Surgery];drug efficacy;drug safety;echography;gene mutation;hemochromatosis/su [Surgery];human;liver biopsy;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/ep [Epidemiology];liver disease/su [Surgery];metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/ep [Epidemiology];metabolic disorder/su [Surgery];phenotype;phlebotomy;prevalence;prognosis;quality of life;review;screening;United States;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];biochemical marker/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];ursodeoxycholic acid/pd [Pharmacology];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy];zinc acetate/pd [Pharmacology],"Mailliard, M. E.;Gollan, J. L.",2003,April,http://dx.doi.org/10.1016/S1521-6918%2802%2900148-8,0,0,
2200,Treatment of Wilson's disease with penicillamine and zinc salts: a follow-up study. [Chinese],"OBJECTIVE: Wilson's disease (WD) is an autosomal recessive disorder characterized by excessive accumulation of copper in the liver and later in the brain and other organs. Penicillamine acts as a reductive chelator. Zinc salts induce the synthesis of metallothionein in cells. Thus these two drugs are theoretically synergistic for the treatment of the disease. However, the two drugs may also have some unfavorable interactions. In this study, the effect of the therapy with combined penicillamine and zinc salts was evaluated based on the follow-up observations of 21 patients with Wilson's disease. METHODS: Using the combined therapy of penicillamine [10-30 mg/(kg.d)] and zinc (22.5 mg, 3 times per day), follow-up study by hospitalization or communication with telephone or mail. RESULTS: Before treatment, all the 21 patients were suffered from chronic liver disorder. Among them, 13 patients (62%) showed to be reactive to the treatment for their liver disorder, 5 patients (24%) died, and 3 patients (14%) dropped off our follow-up study. Among the 5 patients who died, 3 died within 40 days after treatment, one had taken penicillamine only 8 mg/(kg.d), and one died after discontinuation of the treatment by the parents. Of the 12 patients having neurological involvement, neurological symptoms disappeared or markedly improved in 11 patients after treatment. One patient dropped off the follow-up study. The patient with renal tubular acidosis responded well to the treatment. Urine routine analysis was followed up in 6 of the 7 patients with hematuria. Hematuria disappeared in one, became less severe in 1, and remained unchanged in 4 patients. Hypersensitivity to penicillamine was found in one patient. WBC and platelet were found decreased further in 3 patients after the medications. CONCLUSIONS: The combined therapy with penicillamine and zinc salts was effective in treatment of patients with Wilson's disease.",adolescent;article;child;clinical trial;drug combination;female;follow up;human;male;treatment outcome;Wilson disease/dt [Drug Therapy];antidote/ae [Adverse Drug Reaction];antidote/ad [Drug Administration];antidote/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/ad [Drug Administration];zinc/dt [Drug Therapy],"Li, M.;Zhang, Y. H.;Qin, J.",2003,Feb,,0,0,
2201,What have we learnt from CDNA microarray gene expression studies about the role of iron in MPTP induced neurodegeneration and Parkinson's disease?,"There have been numerous hypotheses concerning the etiology and mechanism of dorsal raphe dopaminergic neurodegeneration in Parkinson's disease and its animal models, MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-hydroxydopamine. The advent of cDNA microarray gene expression where expression of thousands of genes can be globally assessed has indicated that mechanism of neurodegeneration by MPTP is a complex cascade of vicious circles. One of these is the alteration of genes associated with iron metabolism, a transitional metal closely associated with inducing the formation of reactive oxygen species and inducing oxidative stress. cDNA gene expression analyses support the established hypothesis of oxidative induced neurodegeneration involving iron deposition in substantia nigra pars compacta (SNPC) parkinsonian brains. The regulation of cellular iron metabolism has been further enhanced by the recent discovery of two iron regulatory proteins, IRP1 and IRP2 which control the level of iron with in the cell. When the cellular level of iron increases IRP2 is degraded by ubiquitination and no further iron accumulates. The reverse occurs when the level of iron is low within the cell. Knock-out IRP1 and IRP2 mice have shown that in latter mice brain iron accumulation precedes the neurodegeneration, ataxia and bradykinesia observed in these animals. Indeed MPTP treatment, which results in iron accumulation in SNCP, abolishes IRP2 with the concomitant increase in alpha-synuclein. Iron chelators such as R-apomorphine and EGCG, which protect against MPTP neurotoxicity, prevent the loss of IRP2 and the increase in alpha-synuclein. The presence of iron together with alpha-synuclein in SNPC may be detrimental for dopaminergic neurons. Since, iron has been shown to cause aggregation of alpha-synuclein to a neurotoxic agent. The use of iron chelators penetrating the blood brain barrier as neuroprotective drugs has been envisaged.","ataxia;blood brain barrier;bradykinesia;cell level;conference paper;DNA microarray;dopaminergic nerve cell;drug design;drug potency;gene expression;gene mutation;human;in situ hybridization;iron metabolism;iron responsive element;knockout mouse;lipid peroxidation;nerve cell necrosis;nerve degeneration/dt [Drug Therapy];nerve degeneration/pc [Prevention];neuroprotection;neurotoxicity/dt [Drug Therapy];neurotoxicity/pc [Prevention];nonhuman;oxidative stress;Parkinson disease/dt [Drug Therapy];Parkinson disease/pc [Prevention];pathophysiology;priority journal;protein degradation;reverse transcription polymerase chain reaction;striatonigral degeneration/dt [Drug Therapy];striatonigral degeneration/pc [Prevention];substantia nigra;ubiquitination;Western blotting;Wilson disease/dt [Drug Therapy];1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine;alpha synuclein;alpha tocopherol/cm [Drug Comparison];alpha tocopherol/dt [Drug Therapy];apomorphine/dt [Drug Therapy];apomorphine/pd [Pharmacology];deferoxamine/dt [Drug Therapy];deferoxamine mesylate/do [Drug Dose];deferoxamine mesylate/dt [Drug Therapy];deferoxamine mesylate/cv [Intracerebroventricular Drug Administration];deferoxamine mesylate/pd [Pharmacology];dopamine;dopamine 1 receptor stimulating agent/dt [Drug Therapy];dopamine 1 receptor stimulating agent/pd [Pharmacology];dopamine 2 receptor stimulating agent/dt [Drug Therapy];dopamine 2 receptor stimulating agent/pd [Pharmacology];ebselen/dt [Drug Therapy];epigallocatechin gallate/dt [Drug Therapy];iron;iron chelating agent/dv [Drug Development];iron chelating agent/do [Drug Dose];iron chelating agent/dt [Drug Therapy];iron chelating agent/cv [Intracerebroventricular Drug Administration];iron chelating agent/ip [Intraperitoneal Drug Administration];iron chelating agent/pd [Pharmacology];iron regulatory protein 1;iron regulatory protein 2;neuroprotective agent/dv [Drug Development];neuroprotective agent/do [Drug Dose];neuroprotective agent/dt [Drug Therapy];neuroprotective agent/cv [Intracerebroventricular Drug Administration];neuroprotective agent/ip [Intraperitoneal Drug Administration];neuroprotective agent/pd [Pharmacology];neurotoxin;penicillamine/dt [Drug Therapy];quinolinol derivative/dv [Drug Development];quinolinol derivative/do [Drug Dose];quinolinol derivative/dt [Drug Therapy];quinolinol derivative/cv [Intracerebroventricular Drug Administration];quinolinol derivative/ip [Intraperitoneal Drug Administration];quinolinol derivative/pd [Pharmacology];reactive oxygen metabolite;scavenger/cm [Drug Comparison];scavenger/dt [Drug Therapy];transition element;unclassified drug;vk 28/dv [Drug Development];vk 28/do [Drug Dose];vk 28/dt [Drug Therapy];vk 28/cv [Intracerebroventricular Drug Administration];vk 28/ip [Intraperitoneal Drug Administration];vk 28/pd [Pharmacology]","Youdim, M. B. H.",2003,,,0,0,
2202,Clinical analysis of hepatolenticular degeneration in children. [Chinese],,adolescent;article;child;female;follow up;human;male;preschool child;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Li, T.;Du, S. L.;Chen, Z. H.",2003,Feb,,0,0,
2203,Wilson disease. [Japanese],,genetics;human;liver transplantation;mutation;psychological aspect;psychotherapy;review;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];Wilson disease/th [Therapy];adenosine triphosphatase;cation transport protein;central muscle relaxant/dt [Drug Therapy];chelating agent/dt [Drug Therapy];Wilson disease protein;zinc/dt [Drug Therapy],"Nagai, Y.",2003,,,0,0,
2204,Nephrolithiasis as an initial clinical manifestation of Wilson-Konovalov disease. [Russian],,adolescent;adult;article;case report;differential diagnosis;female;human;liver cirrhosis/et [Etiology];male;middle aged;nephrolithiasis/et [Etiology];obesity/co [Complication];treatment outcome;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Rakhimova, O. I.;Rozina, T. P.;Ignatova, T. M.",2003,,,0,0,
2205,Wilson disease in 2003. [Hungarian],"The actuality of this review is based on the results of a recent international consensus conference on the diagnosis and phenotypic classification of Wilson disease published in 2003. The mechanism of the genetically determined copper elimination failure and the copper toxicity, the clinical presentation forms, the diagnosis and treatment of the disease is reviewed. Wilson disease should be taken into consideration in case of any liver disease of unknown origin or neuropsychiatric symptoms. The internationally accepted scoring system is presented.",classification;differential diagnosis;family planning;genetic counseling;genetics;genotype;human;metabolism;phenotype;review;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy];adenosine triphosphatase;cation transport protein;chelating agent/dt [Drug Therapy];copper;molybdenum/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid;trientine/dt [Drug Therapy];Wilson disease protein;zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Szalay, F.",2003,14 Dec,,0,0,
2206,D-penicillamine and plasmapheresis in acute liver failure secondary to Wilson's disease,"We report a case of a 19-year-old woman with acute liver failure, Coombs' negative hemolytic anemia, and renal failure as initial manifestations of Wilson's disease with recovery following medical treatment. The clinical picture and low serum transaminase and alkaline phosphatase levels gave us a clue to suspect Wilson's disease and to initiate plasmapheresis and D-penicillamine soon after admission. The serum and urinary copper levels were elevated with low serum ceruloplasmin. We proceeded to ambulatory follow-up with medical treatment with D-penicillamine. A few months later, during the course of a laparoscopic cholecystectomy because of symptomatic gallstone disease, a liver biopsy sample was obtained that showed histological liver fibrosis and strongly elevated levels of liver tissue copper.",Anemia;Hemolytic;Liver failure;Penicillamine;Plasmapheresis;adult;article;case report;cholecystectomy;clinical feature;Coombs test;copper blood level;drug hypersensitivity/dt [Drug Therapy];drug hypersensitivity/si [Side Effect];enzyme blood level;female;follow up;gallstone;hemolytic anemia;histology;human;human tissue;liver biopsy;liver failure/co [Complication];liver failure/di [Diagnosis];liver fibrosis/co [Complication];liver fibrosis/di [Diagnosis];pruritus/dt [Drug Therapy];pruritus/si [Side Effect];rash/dt [Drug Therapy];rash/si [Side Effect];symptomatology;thrombocytopenia/co [Complication];tissue level;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];alkaline phosphatase/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology],"Rodriguez-Farina, E.;Tremosa Llurba, G.;Xiol Quingles, X.;Lores Obradors, A.;Castellote Alonso, J.;Gornals Soler, J. B.;Lopez Nunez, C.",2003,01 Jan,,0,0,465
2207,Metals and water,,alga;allergic reaction;Alzheimer disease;anemia;aquatic environment;dementia;digestive system injury;environmental factor;environmental impact;fluid intake;human;learning disorder;note;particle resuspension;pH;practice guideline;priority journal;species;water hardness;Wilson disease;world health organization;aluminum/to [Drug Toxicity];antimony;cadmium;chromium;copper/to [Drug Toxicity];drinking water;fulvic acid;humic acid;iron/to [Drug Toxicity];lead/to [Drug Toxicity];metal derivative/to [Drug Toxicity];neurotoxin/to [Drug Toxicity];nickel/to [Drug Toxicity];selenium;water;zinc,"Fawell, J.",2004,August,http://dx.doi.org/10.1039/b410290h,0,0,
2208,Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma,"Aim: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-likel receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain, and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma. Methods: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases. Results: Although nociceptin levels were elevated in patients with Wilson disease (14.0+/-2.7 pg/mL, n=26), primary biliary cirrhosis (12.1+/-3.2 pg/mL, 17=21) and liver cirrhosis (12.8+/-4.0 pg/mL, n=15) compared to the healthy controls (9.2+/-1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found (105.9+/-14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9+/-14.9 pg/mL, n=12) and without (107.7+/-14.5 pg/mL, n=6). Conclusion: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.",adult;aged;article;bilirubin blood level;chronic liver disease/et [Etiology];chronic pain;clinical article;cognition;controlled study;echography;female;human;imaging system;liver cell carcinoma/dt [Drug Therapy];liver cell carcinoma/et [Etiology];male;needle biopsy;pain;pain assessment;primary biliary cirrhosis/dt [Drug Therapy];primary biliary cirrhosis/et [Etiology];protein blood level;radioimmunoassay;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alkaline phosphatase/ec [Endogenous Compound];alpha fetoprotein/ec [Endogenous Compound];analgesic agent/dt [Drug Therapy];aprotinin;bilirubin/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];nociceptin/ec [Endogenous Compound];opiate receptor/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];proteinase inhibitor;ursodeoxycholic acid/dt [Drug Therapy],"Szalay, F.;Hantos, M. B.;Horvath, A.;Lakatos, P. L.;Folhoffer, A.;Dunkel, K.;Hegedus, D.;Tekes, K.",2004,January,,0,0,
2209,Tetrathiomolybdate in the treatment of acute hepatitis in an animal model for Wilson disease,"Background/Aims: Tetrathiomolybdate (TTM) is a potent copper-chelating agent that has been shown to be effective in Wilson disease patients with neurological symptoms. Here, we investigate the potential use of TTM in treating the acute hepatic copper toxicosis in Long-Evans Cinnamon (LEC) rats, an authentic model for Wilson disease. Methods: After the onset of acute hepatitis, LEC rats were treated once with 10 mg TTM/kg. After 1 and 4 days, parameters of liver toxicity and the subcellular distribution and binding of copper and iron were studied. Results: In 11 out of 12 rats TTM rapidly improved acute hepatitis. Hepatic copper decreased through removal from cytosolic metallothionein and lysosomal metallothionein polymers. The remaining lysosomal copper forms a metallothionein-copper-TTM complex. In an almost moribund rat, however, TTM caused severe hepatotoxicity with fatal outcome. Conclusions: TTM is effective in treating acute hepatitis in LEC rats when applied before the animals become moribund. TTM appears to act by removing the presumable reactive copper associated to lysosomal metallothionein polymers. The remaining lysosomal copper seems to be inactivated by forming a complex with TTM. Moreover, TTM removes copper from cytosolic copper-containing metallothionein. As a consequence, metallothionein is degraded and the uptake of copper-metallothionein into the lysosomes and the formation of the metallothionein polymer associated copper is reduced. © 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",Ammonium tetrathiomolybdate;Copper toxicity;Hepatitis;Iron overload;Long-Evans Cinnamon rat;Therapy;Wilson disease;acute hepatitis/dt [Drug Therapy];animal experiment;animal model;animal tissue;article;cellular distribution;controlled study;dying;fatality;female;intoxication;liver toxicity;lysosome;nonhuman;priority journal;rat;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];chelating agent/ip [Intraperitoneal Drug Administration];copper;iron;metallothionein;polymer;tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/ip [Intraperitoneal Drug Administration],"Klein, D.;Arora, U.;Lichtmannegger, J.;Finckh, M.;Heinzmann, U.;Summer, K. H.",2004,March,http://dx.doi.org/10.1016/j.jhep.2003.11.034,0,0,
2210,Journal of Hepatology: Editorial,,bone marrow toxicity/si [Side Effect];cell fractionation;disease severity;editorial;electron microscopy;genetic variability;haplotype;hepatitis B/dt [Drug Therapy];human;immunopathogenesis;liver toxicity/si [Side Effect];major histocompatibility complex;nonhuman;primary sclerosing cholangitis;priority journal;side effect/si [Side Effect];skin manifestation/si [Side Effect];Wilson disease/dt [Drug Therapy];X ray microanalysis;antivirus agent/dt [Drug Therapy];azathioprine/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];thiopurine methyltransferase,Anonymous,2004,March,http://dx.doi.org/10.1016/S0168-8278%2804%2900031-5,0,0,
2211,Genotype-phenotype correlations for a wide spectrum of mutations in the Wilson disease gene (ATP7B),"Wilson disease (WND) is caused by mutations in the ATP7B gene and exhibits substantial allelic heterogeneity. In this study we report the results of molecular analyses of 20 WND families not described previously. When combined with our prior results, the cohort includes 93 index patients from 69 unrelated families. Twenty different mutations accounted for 86% of the WND chromosomes. The most frequent were p.H1069Q (35%), p.R969Q (12%), c.2530delA (7%), p.L936X (7%), p.Q289X (7%), and P.I1148T (3%). We also present here a detailed phenotypic assessment for patients whose molecular result was previously reported. Thirty cases were homozygous for 9 different mutations, 13 of which were homozygous for p.H1069Q, and 7 for p.R969Q. Mutations p.H1069Q and p.R969Q appeared to confer a milder disease as patients showed disease onset at a later age, and were associated with milder severity when found in trans with severe mutations. Predicted nonsense and frameshift mutations were associated with severe phenotypic expression with earlier disease onset and lower ceruloplasmin values. WND can be treated by copper-chelation therapy, particularly if the disease is diagnosed before irreversible tissue damage occurs. Our results on the effect of predicted nonsense and frameshift mutations are especially important for early medical intervention in presymptomatic infants and children with these genotypes. © 2004 Wiley-Liss, Inc.",atp7b;Genotype-phenotype;Molecular genetic diagnosis;Mutations;Wilson disease;adolescent;adult;article;ATP7B gene;chelation;cohort analysis;controlled study;disease severity;DNA sequence;frameshift mutation;gene;gene mutation;genotype;Greece;human;human tissue;liver disease/di [Diagnosis];liver disease/et [Etiology];major clinical study;molecular genetics;neurologic disease/di [Diagnosis];neurologic disease/et [Etiology];nonsense mutation;nucleotide sequence;onset age;phenotype;polymerase chain reaction;priority journal;single strand conformation polymorphism;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;genomic DNA;penicillamine;trientine;zinc derivative,"Panagiotakaki, E.;Tzetis, M.;Manolaki, N.;Loudianos, G.;Papatheodorou, A.;Manesis, E.;Nousia-Arvanitakis, S.;Syriopoulou, V.;Kanavakis, E.",2004,01 Dec,http://dx.doi.org/10.1002/ajmg.a.30345,0,0,
2212,Wilson's disease - Unusual features,"Two cases of Wilson's disease with unusual features are reported. In one case neurological abnormality was the presenting feature without any clinical involvement of the liver. In the other case, neurologic manifestations were associated with rickets and cholelithiasis, a result of chronic hemolytic state. Apart from clinical profile both the cases were diagnosed by grossly reduced serum ceruloplasmin level. However, Kayser-Fleischer rings were found in each case.",Cholelithiasis;Kayser-Fleischer rings;Wilson's disease;article;case report;ceruloplasmin blood level;clinical feature;female;hemolysis;human;kayser fleischer ring;liver disease;neurologic disease;ophthalmoscopy;rickets;school child;slit lamp;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration],"Ghosh, J. B.;Chakrabarty, S.;Singh, A. K.;Gupta, D.",2004,October,,0,0,
2213,A case of Wilson's disease with diffuse golden-brown opacity in the posterior lens capsule. [Japanese],"Background : We report a case of Wilson's disease with a typical Kayser-Fleischer ring and an unusual posterior lens capsule opacity. Case Report : A 27-year-old male with Wilson's disease came to Tottori University Hospital 7 years after stopping D-penicillamine therapy, which he had taken for 12 years. His corrected visual acuity was 1.2 bilaterally. Slit lamp examination disclosed bilateral Kayser-Fleischer rings in the peripheral cornea with golden-brown opacity in the posterior lens capsule, without sunflower cataract in the anterior lens capsule. Conclusions : This case of Wilson's disease with only posterior lens capsule opacity without sunflower cataract is very rare. We speculate that the difference in progression of opacity in the anterior and posterior lens capsule was related to the effects of D-penicillamine therapy on ionic copper in the aqueous humor.",D-Penicillamine;Diffuse Posterior Lens Capsular Opacity;Kayser-Fleischer Ring;Wilson's Disease;adult;aqueous humor;article;case report;cataract/co [Complication];cataract/et [Etiology];disease course;human;lens capsule;male;visual acuity;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Komatsu, N.;Sasaki, Y.;Baba, T.;Inoue, Y.",2004,September,,0,0,
2214,Juvenile emphysema in a patient receiving long-term administration of D-penicillamine for wilson's disease. [Japanese],"A 27-year-old male, a current smoker, had been diagnosed as having Wilson's disease at 13 years of age, based on slurred speech and tremors. He had been receiving D-penicillamine for 14 years, when he was hospitalized with severe dyspnea and hypoxemia. Pulmonary function tests indicated airflow obstruction, and low attenuation areas were noted by high-resolution computed tomography of the chest. To rule out obstructive bronchiolitis, he underwent thoracoscopic biopsy. Microscopic observation of the lung tissues showed emphysematous changes in both the centrilobular and subpleural areas, with massive elastosis on the walls. Striking elastosis was also evident in the bronchiolar wall. Although the coincidental co-existence of both Wilson's disease and juvenile emphysema could not be discounted, it is speculated that the prolonged administration of D-penicillamine, which is a known lathyrogen, might have caused juvenile emphysema in this case. Thus, cessation of smoking should be advised for patients receiving D-penicillamine in a case such as this.",D-penicillamine;Elastosis;Juvenile emphysema;Wilson's disease;adult;airway obstruction/di [Diagnosis];article;case report;clinical feature;endoscopic biopsy;high resolution computer tomography;human;human tissue;lung emphysema/di [Diagnosis];lung emphysema/si [Side Effect];lung function test;male;smoking cessation;thoracoscopy;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Usuki, J.;Suzuki, M.;Sakakibara, K.;Enomoto, T.;Azuma, A.;Yoshimura, A.;Kida, K.;Kunugi, S.;Fukuda, Y.;Kudoh, S.",2004,,,0,0,
2215,Strokelike presentation of Wilson disease with homozygosity for a novel T766R mutation,,adolescent;article;case report;clinical feature;computer assisted tomography;DNA sequence;dysarthria;dysphagia;gene mutation;genotype;homozygosity;human;male;nuclear magnetic resonance imaging;physical examination;priority journal;slit lamp;slurred speech;stroke;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Pendlebury, S. T.;Rothwell, P. M.;Dalton, A.;Burton, E. A.",2004,23 Nov,,0,0,
2216,Rare presentation of Wilson's disease: A case report,"A female presented with pain in left flank, detected to have bilateral renal calculi with deranged liver functions. On investigation found her to have Wilson's disease with hypercalciuria and incomplete distal renal tubular acidosis. Patient was started on penicillamine following which her hepatitis improved but hypercalciuria persisted after 10 weeks of follow up. The rarity of such presentation and literature review for the same is discussed. © 2004 Kluwer Academic Publishers.",Hepatitis;Incomplete RTA;Renal stones;Wilson's disease;adult;anamnesis;article;case report;clinical feature;disease association;echography;female;flank pain;follow up;hepatitis/di [Diagnosis];hepatitis/dt [Drug Therapy];human;hypercalciuria;intravenous urography;kidney distal tubule;kidney tubule acidosis;laboratory test;liver dysfunction;medical assessment;medical literature;nephrolithiasis;renography;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Kalra, V.;Mahajan, S.;Kesarwani, P. K.",2004,,http://dx.doi.org/10.1023/B:UROL.0000034630.73124.36,0,0,
2217,"Inhibitory effects of trientine, a copper-chelating agent, on induction of DNA strand breaks in hepatic cells of Long-Evans Cinnamon rats","Effects of treatment with trientine, a specific copper-chelating agent, on accumulation of copper and induction of DNA strand breaks were investigated in Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson's disease. Copper accumulated in the livers of LEC rats in an age-dependent manner from 4 to 13 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, hepatic copper contents did not increase and were maintained at the same levels as those in 10-week-old LEC rats. When the amounts of DNA single-strand breaks (SSBs) were estimated by a comet assay, SSBs of DNA were induced in a substantial population of LEC rat hepatic cells around 8 weeks of age and the amounts of SSBs increased in an age-dependent manner from 8 to 15 weeks of age. When LEC rats were treated with trientine from 10 weeks of age, the observed number of cells with DNA damage decreased dramatically, suggesting that induction of SSBs of DNA was inhibited and/or SSBs were repaired during the period of treatment with trientine. The results show that treatment of LEC rats with trientine decreases the number of DNA strand breaks observed, although copper contents remain high in the liver. © 2004 Elsevier B.V. All rights reserved.",Copper;DNA strand break;Hepatic cell;LEC rat;Trientine;animal cell;animal experiment;animal model;animal tissue;article;comet assay;controlled study;disease model;DNA damage;DNA strand breakage;drug effect;experimental rat;liver cell;male;nonhuman;priority journal;rat;rat strain;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];chelating agent/to [Drug Toxicity];chelating agent/po [Oral Drug Administration];chelating agent/pd [Pharmacology];copper/ec [Endogenous Compound];DNA/ec [Endogenous Compound];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];trientine/po [Oral Drug Administration];trientine/pd [Pharmacology],"Hayashi, M.;Miyane, K.;Hirooka, T.;Endoh, D.;Higuchi, H.;Nagahata, H.;Nakayama, K.;Kon, Y.;Okui, T.",2004,01 Nov,http://dx.doi.org/10.1016/j.bbagen.2004.07.006,0,0,
2218,Metal binding properties of the Wilson protein. [Chinese],"Objective: To investigate the copper transporting ability of Wilson protein, and the mechanism of zinc therapy. Methods: Using RT-PCR to amplify a 1.95 kb copper binding domain fragment of Wilson protein (WCBD) and cloning it to pGEX-4T-1, the GST-WCBD was expressed in BL-21 under the IPTG induction. Purified the GST-WCBD with GST-columns, cleaved the GST part with Thrombin and acquired the WCBD. The metal binding properties to Cu(II), Zn(II), Fe(III), Ni(II), Ag(I) with IMAC and <sup>65</sup>Zn blotting analysis were carried out. Results: The WCBD was found having varying affinities with different metals as follow: Cu(I) > Zn(II) > Ni(II) > Cu(II). Zn(II) was discovered able to compete with Cu(I) in the binding domain. Conclusion: Wilson protein delivering copper as Cu(I) was suggested to be demonstrated. The capacity of zinc to compete with copper may be a mechanism in zinc treatment to this disease.",Adenosinetriphosphatase;Binding;Competitive;Copper;Cution transport proteins;Hepatolenticular degeneration;Zinc;article;metal binding;molecular cloning;radioassay;reverse transcription polymerase chain reaction;Wilson disease;cation transport protein;copper ion;ferric ion;metal ion;nickel;silver;thrombin;unclassified drug;wilson protein;zinc ion,"Feng, Y. Q.;Liang, X. L.;Wang, Y.;Guo, N.;Chen, X.;Xu, L.;Huang, F.",2004,23 Feb,,0,0,
2219,Copper chelation as an antiangiogenic therapy,"Angiogenesis is now recognized as a crucial process in tumor development. Copper appears to act as an essential cofactor for several angiogenic growth factors, and both copper metabolism and ceruloplasmin expression are upregulated in many tumors. The role of copper chelators has been investigated in animal models with promising results. New therapies for Wilson's disease (a disease of copper accumulation) have enabled clinical trials of copper chelation to be undertaken. Here we discuss the evidence for a role of copper in angiogenesis and possible mechanisms of action of anticopper agents.",Angiogenesis;Antiangiogenic therapy;Chelation;Copper;animal experiment;animal model;antiangiogenic activity;ceruloplasmin blood level;chelation therapy;clinical trial;copper metabolism;drug mechanism;human;nonhuman;phase 1 clinical trial;phase 2 clinical trial;priority journal;protein expression;review;tumor growth;upregulation;Wilson disease/dt [Drug Therapy];angiogenic factor;ceruloplasmin;chaperone;chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];cisplatin;copper chelating agent/dt [Drug Therapy];copper chelating agent/pd [Pharmacology];copper zinc superoxide dismutase;cyclooxygenase 2;growth factor;immunoglobulin enhancer binding protein;penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];prion protein;protein S 100;protein S 100A13;tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/ad [Drug Administration];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration];tetrathiomolybdic acid/pd [Pharmacology];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];unclassified drug,"Lowndes, S. A.;Harris, A. L.",2004,,,0,0,
2220,Role of antioxidants in clinical practice,"Free radicals are extremely reactive compounds that damage vital molecules of cells and cause various diseases including retinopathy of prematurity, bonchopulmonary dysplasia, neonatal necrotizing enterocolitis, Wilson's disease, cholestatic liver diseases etc. They are continuously produced in our body and are neutralized by enzymatic and dietary antioxidants. Extensive tissue damage will occur if there are not enough antioxidants to neutralize free radicals. Fruits and vegetables are excellent sources of antioxidants. It is important to include at least 5 servings of fruits and vegetables in our daily diet.",Dietary antioxidants;Enzymatic antioxidants;Free radical induced diseases;Free radicals;Plant antioxidants;alcohol liver disease/dt [Drug Therapy];antineoplastic activity;antioxidant activity;article;bladder cancer/dt [Drug Therapy];bladder cancer/pc [Prevention];brain ischemia/dt [Drug Therapy];breast cancer/dt [Drug Therapy];breast cancer/pc [Prevention];cardiovascular disease/dt [Drug Therapy];cardiovascular disease/pc [Prevention];clinical practice;clinical trial;colon cancer/dt [Drug Therapy];colon cancer/pc [Prevention];dietary intake;duodenum cancer/dt [Drug Therapy];esophagus cancer/dt [Drug Therapy];fruit;gallbladder disease/dt [Drug Therapy];hepatitis/dt [Drug Therapy];human;Human immunodeficiency virus infection/pc [Prevention];liver cancer/dt [Drug Therapy];liver cancer/pc [Prevention];liver cirrhosis/dt [Drug Therapy];liver disease/dt [Drug Therapy];liver disease/et [Etiology];lung cancer/dt [Drug Therapy];lung cancer/pc [Prevention];lung dysplasia/dt [Drug Therapy];lung dysplasia/et [Etiology];lung dysplasia/pc [Prevention];necrotizing enterocolitis/et [Etiology];nonhuman;nutrient content;oxidative stress;pancreas cancer/dt [Drug Therapy];pancreatitis/et [Etiology];prostate cancer/dt [Drug Therapy];prostate cancer/pc [Prevention];retrolental fibroplasia/dt [Drug Therapy];retrolental fibroplasia/et [Etiology];skin cancer/dt [Drug Therapy];skin cancer/pc [Prevention];spleen disease/dt [Drug Therapy];stomach cancer/dt [Drug Therapy];tissue injury/et [Etiology];vegetable;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha carotene;alpha tocopherol/ct [Clinical Trial];alpha tocopherol/cm [Drug Comparison];alpha tocopherol/dt [Drug Therapy];alpha tocopherol/pd [Pharmacology];antioxidant/cm [Drug Comparison];antioxidant/dt [Drug Therapy];antioxidant/pd [Pharmacology];ascorbic acid/cm [Drug Comparison];ascorbic acid/pd [Pharmacology];beta carotene;calcium channel blocking agent/dt [Drug Therapy];carotenoid/pd [Pharmacology];catalase/ec [Endogenous Compound];copper zinc superoxide dismutase/dt [Drug Therapy];copper zinc superoxide dismutase/tr [Intratracheal Drug Administration];daidzein/pd [Pharmacology];epicatechin/dt [Drug Therapy];epicatechin/pd [Pharmacology];epicatechin gallate/dt [Drug Therapy];epicatechin gallate/pd [Pharmacology];epigallocatechin/dt [Drug Therapy];epigallocatechin/pd [Pharmacology];epigallocatechin gallate/dt [Drug Therapy];epigallocatechin gallate/pd [Pharmacology];flavonoid;free radical/ec [Endogenous Compound];genistein/dt [Drug Therapy];genistein/pd [Pharmacology];glutathione peroxidase/ec [Endogenous Compound];green tea extract/cm [Drug Comparison];green tea extract/dt [Drug Therapy];green tea extract/pd [Pharmacology];isoflavone derivative/dt [Drug Therapy];isoflavone derivative/pd [Pharmacology];lycopene/dt [Drug Therapy];lycopene/pd [Pharmacology];major histocompatibility antigen class 2/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];retinol/dt [Drug Therapy];selenium;silymarin/dt [Drug Therapy];silymarin/pd [Pharmacology];superoxide dismutase/ec [Endogenous Compound];trace element/pd [Pharmacology];unindexed drug;zinc/dt [Drug Therapy],"Riyaz, A.",2004,July/September,,0,0,
2221,Wilson's disease: A review,,autoimmune disease/si [Side Effect];autosomal recessive disorder;bioaccumulation;clinical feature;copper blood level;copper metabolism;diagnostic test;diet therapy;drug dose regimen;drug efficacy;drug hypersensitivity/si [Side Effect];drug mechanism;drug tolerability;enzyme activity;eosinophilia/si [Side Effect];extrapyramidal symptom/co [Complication];fever/si [Side Effect];gene identification;Goodpasture syndrome/si [Side Effect];hemorrhagic gastritis/si [Side Effect];human;inborn error of metabolism/dt [Drug Therapy];inborn error of metabolism/et [Etiology];intestine absorption;leukopenia/si [Side Effect];lipid peroxidation;liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver level;liver toxicity/si [Side Effect];liver transplantation;lupus erythematosus/si [Side Effect];lupus erythematosus nephritis/si [Side Effect];lymphadenopathy/si [Side Effect];myasthenia/si [Side Effect];nephritis/si [Side Effect];neuroimaging;neurologic disease;pancreatitis/si [Side Effect];pathophysiology;practice guideline;prevalence;prognosis;protein blood level;protein synthesis;protein synthesis inhibition;rash/si [Side Effect];review;sideroblastic anemia/si [Side Effect];slit lamp;splenomegaly/si [Side Effect];stomach disease/si [Side Effect];thrombocytopenia/si [Side Effect];urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];antioxidant/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];copper/to [Drug Toxicity];DNA/ec [Endogenous Compound];free radical/ec [Endogenous Compound];glycoprotein/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pyridoxine;tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/dt [Drug Therapy];zinc derivative/pd [Pharmacology],"Hassan, A.;Masood, F.",2004,September,,0,0,
2222,Subchondral cyst of the tibia secondary to Wilson disease,"We present the case of a 40-year-old male patient who had been suffering from Wilson disease for over 20 years, whose knee was diagnosed as osteoarthritis combined with subchondral cyst of the tibia. Preoperative examinations (X-ray, CT and MRI) confirmed the diagnosis. The microscopic examination detected thickening of the synovial membrane, and histopathological findings revealed that lymphoid cells and plasma cells were infiltrated at the synovial membrane. On copper-specific staining, no copper pigmentation was identified. However, the energy-dispersive X-ray (EDX) microanalysis revealed copper pigmentation in high concentration. These findings may contribute to our better comprehension of the development process of the arthropathy in patients with Wilson disease. The combination of subchondral cyst with Wilson disease is extremely rare, as only about 16 such cases have been reported in the English literature. © Clinical Rheumatology 2004.",Energy-dispersive X-ray (EDX);Total knee arthroplasty;Wilson's disease;adult;arthropathy/di [Diagnosis];article;bone cyst/di [Diagnosis];case report;cell infiltration;comorbidity;computer assisted tomography;disease course;histopathology;human;human cell;human tissue;knee osteoarthritis/di [Diagnosis];lymphoid cell;male;medical literature;microscopy;nuclear magnetic resonance imaging;pigmentation;plasma cell;preoperative evaluation;priority journal;synovium;thickness;tibia;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];X ray microanalysis;copper;penicillamine/dt [Drug Therapy],"Kataoka, M.;Tsumura, H.;Itonaga, I.;Kaku, N.;Torisu, T.",2004,October,http://dx.doi.org/10.1007/s10067-004-0913-8,0,0,
2223,A case of Wilson's disease treated with living donor-liver transplantation because of acquired sideroblastic anemia. [Japanese],,adolescent;article;case report;female;human;liver transplantation;living donor;serology;sideroblastic anemia/di [Diagnosis];sideroblastic anemia/su [Surgery];Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];penicillamine/do [Drug Dose],"Hasebe, A.;Michitaka, K.;Abe, M.;Tokumoto, Y.;Furukawa, S.;Kumagi, T.;Minami, H.;Horiike, N.;Onji, M.;Kobayasi, N.",2004,,,0,0,
2224,Postural tremor in Wilson's disease: A magnetoencephalographic study,"The following study included 5 Wilson's disease (WD) patients showing a right-sided postural forearm tremor (4-6 Hz) and addressed the question of whether the primary motor cortex (M1) is involved in tremor generation. Using a 122-channel whole-head neuromagnetometer and surface electromyogram (EMG), we investigated cerebromuscular coupling. Postural tremor was observed in a sustained 45-degree posture of the right-sided forearm. Data were analyzed using dynamic imaging of coherent sources (DICS), revealing cerebromuscular coupling between EMG and cerebral activity. Coherent sources were superimposed on individual high-resolution T1-weighted magnetic resonance images (MRI). Phase lags between EMG and cerebral areas showing strongest coherence were determined by means of a Hilbert transform of both signals. In all patients, postural tremor was associated with strong coherence between tremor EMG and activity in contralateral primary sensorimotor cortex (S1/M1) at tremor or double tremor frequency. Phase lag values between S1/M1 activity and EMG revealed efferent and afferent components in the corticomuscular coupling. Taken together, our results indicate that postural tremor in WD is mediated through a pathological oscillatory drive from the primary motor cortex. © 2004 Movement Disorder Society.",Coherence;dics;meg;mri;Tremor;Wilson's disease;adult;article;brain region;clinical article;controlled study;data analysis;electromyography;forearm;frequency analysis;human;individualization;magnetoencephalography;male;motor cortex;neuromuscular function;nuclear magnetic resonance imaging;oscillation;postural tremor;priority journal;sensorimotor cortex;signal transduction;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Sudmeyer, M.;Pollok, B.;Hefter, H.;Gross, J.;Wojtecki, L.;Butz, M.;Timmermann, L.;Schnitzler, A.",2004,December,http://dx.doi.org/10.1002/mds.20240,0,0,
2225,Movement disorders in pregnancy,"Movement disorders are not particularly common during pregnancy, with a few exceptions. RLS occurs most commonly followed by CG. Currently, with the incidence of rheumatic fever lower than previously, any woman who develops CG should be checked for illness other than rheumatic heart disease. The differential includes systemic lupus erythromatosis and antiphospholipid antibody syndrome [21]. Regarding the use of dopaminergic agents, the dopamine agonist, pergolide, can be maintained during pregnancy for the treatment of PD, Segawa disease, and RLS. The use of levodopa and ropinirole should be limited during pregnancy because of the possible teratogenic effects. Amantadine is contraindicated during pregnancy [54]. The data on selegiline are controversial; animal studies show possible serotonergic effects [52] and teratogenic effects [53]. If treatment is indicated in patients who have Tourette syndrome, the high potency neuroleptics drugs (haloperidol) are preferred to treat associated symptoms [38]. Depression is a common comorbidity in patients who have PD, HD, Tourette syndrome, or other chronic neurologic diseases. Depression treatment during pregnancy is covered by Levy et al elsewhere in this issue. As discussed previously, most of the data on the use of drugs during pregnancy, especially the dopaminergic agents, are limited to animal studies and case reports. Therefore, it is in part left to the neurologist to decide on treatment based on the individual patient, clinical judgment, and inferences from animal studies and limited case reports.",agenesis;anteverted nostril/si [Side Effect];antiphospholipid syndrome;apathy;attention deficit disorder;behavior disorder;cardiovascular malformation/si [Side Effect];chelation therapy;chorea/dt [Drug Therapy];chorea/et [Etiology];connective tissue disease;cutis laxa/si [Side Effect];depression/co [Complication];drug safety;dystonia/dt [Drug Therapy];dystonia/et [Etiology];essential tremor/dt [Drug Therapy];extrapyramidal symptom/si [Side Effect];fetus malformation;finger malformation;Gilles de la Tourette syndrome/co [Complication];Gilles de la Tourette syndrome/dt [Drug Therapy];growth retardation/si [Side Effect];hirsutism/si [Side Effect];human;Huntington chorea/dt [Drug Therapy];hyperactivity/si [Side Effect];hyperthermia/co [Complication];infection;inguinal hernia/si [Side Effect];intrauterine growth retardation;iron deficiency anemia;irritability;low birth weight;low set ear/si [Side Effect];mental disease/co [Complication];micrognathia/si [Side Effect];mood disorder/co [Complication];motor dysfunction/co [Complication];motor dysfunction/dt [Drug Therapy];motor dysfunction/et [Etiology];myoglobinuria/co [Complication];nail hypoplasia/si [Side Effect];neural tube defect/dt [Drug Therapy];neural tube defect/pc [Prevention];nonhuman;obsessive compulsive disorder/dt [Drug Therapy];Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];personality disorder/co [Complication];polyneuropathy;pregnancy;priority journal;restless legs syndrome/co [Complication];restless legs syndrome/dt [Drug Therapy];restless legs syndrome/et [Etiology];restlessness/si [Side Effect];review;rhabdomyolysis/co [Complication];rheumatic fever;seizure/dt [Drug Therapy];short nose/si [Side Effect];side effect/si [Side Effect];spontaneous abortion/si [Side Effect];systemic lupus erythematosus;teratogenicity;uremia;vertebra malformation;visual disorder;vitamin supplementation;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];anticonvulsive agent/dt [Drug Therapy];antiparkinson agent/ae [Adverse Drug Reaction];antiparkinson agent/cb [Drug Combination];antiparkinson agent/do [Drug Dose];antiparkinson agent/dt [Drug Therapy];antiparkinson agent/to [Drug Toxicity];antiparkinson agent/pk [Pharmacokinetics];antiparkinson agent/pd [Pharmacology];aromatic levo amino acid decarboxylase/cb [Drug Combination];aromatic levo amino acid decarboxylase/dt [Drug Therapy];benzodiazepine derivative/dt [Drug Therapy];botulinum toxin A/do [Drug Dose];botulinum toxin A/dt [Drug Therapy];botulinum toxin A/to [Drug Toxicity];botulinum toxin B;butyrophenone derivative/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];carbidopa/ae [Adverse Drug Reaction];carbidopa/cb [Drug Combination];carbidopa/dt [Drug Therapy];clonazepam/dt [Drug Therapy];decarboxylase inhibitor/ae [Adverse Drug Reaction];decarboxylase inhibitor/cb [Drug Combination];decarboxylase inhibitor/dt [Drug Therapy];decarboxylase inhibitor/to [Drug Toxicity];dextropropoxyphene/dt [Drug Therapy];dopamine receptor blocking agent/dt [Drug Therapy];dopamine receptor stimulating agent/ae [Adverse Drug Reaction];dopamine receptor stimulating agent/cb [Drug Combination];dopamine receptor stimulating agent/dt [Drug Therapy];dopamine receptor stimulating agent/to [Drug Toxicity];folic acid/dt [Drug Therapy];gabapentin/ae [Adverse Drug Reaction];gabapentin/dt [Drug Therapy];gabapentin/to [Drug Toxicity];levodopa/ae [Adverse Drug Reaction];levodopa/cb [Drug Combination];levodopa/dt [Drug Therapy];levodopa/to [Drug Toxicity];levodopa/pk [Pharmacokinetics];methadone/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/do [Drug Dose];neuroleptic agent/dt [Drug Therapy];opiate/dt [Drug Therapy];oxycodone/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];pergolide/ae [Adverse Drug Reaction];pergolide/dt [Drug Therapy];pergolide/to [Drug Toxicity];phenothiazine/dt [Drug Therapy];primidone/ae [Adverse Drug Reaction];primidone/dt [Drug Therapy];propanol/ae [Adverse Drug Reaction];propanol/dt [Drug Therapy];reserpine/dt [Drug Therapy];ropinirole/do [Drug Dose];ropinirole/to [Drug Toxicity];sulpiride/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];unindexed drug,"Smith, M. S. A.;Evatt, M. L.",2004,November,http://dx.doi.org/10.1016/j.ncl.2004.06.005,0,0,
2226,Iatrogenic copper deficiency following information and drugs obtained over the internet,We report the case of a 56-year-old woman with a 7-year history of metastatic cancer who presented with severe copper deficiency following self-treatment with the copper-chelating agent tetrathiomolybdate. This compound was used with the aim of inhibiting tumour angiogenesis and was obtained from the USA by placing an order on the internet. The patient exhibited severe neutropenia as her serum copper concentration fell from 19.8 mumol/L to 3.3 mumol/L and her caeruloplasmin concentration from 35 mg/dL to 4 mg/dL.,adult;alternative medicine;anemia;angiogenesis;article;cancer chemotherapy;case report;chelation;copper blood level;copper deficiency/di [Diagnosis];copper deficiency/et [Etiology];copper deficiency/si [Side Effect];disease course;female;human;iatrogenic disease/co [Complication];iatrogenic disease/si [Side Effect];Internet;kidney cancer/dt [Drug Therapy];leukocyte count;liver metastasis/co [Complication];liver metastasis/di [Diagnosis];liver metastasis/dt [Drug Therapy];liver metastasis/rt [Radiotherapy];neutropenia/co [Complication];neutropenia/si [Side Effect];priority journal;rectum carcinoma/su [Surgery];self medication;treatment outcome;Wilson disease/dt [Drug Therapy];antineoplastic agent/ad [Drug Administration];antineoplastic agent/cb [Drug Combination];antineoplastic agent/dt [Drug Therapy];antineoplastic agent/ia [Intraarterial Drug Administration];antineoplastic agent/po [Oral Drug Administration];capecitabine/ad [Drug Administration];capecitabine/dt [Drug Therapy];capecitabine/po [Oral Drug Administration];carcinoembryonic antigen/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;fluorouracil/ad [Drug Administration];fluorouracil/cb [Drug Combination];fluorouracil/dt [Drug Therapy];fluorouracil/ia [Intraarterial Drug Administration];folinic acid/cb [Drug Combination];folinic acid/dt [Drug Therapy];oxaliplatin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy],"Lang, T. F.;Glynne-Jones, R.;Blake, S.;Taylor, A.;Kay, J. D. S.",2004,September,http://dx.doi.org/10.1258/0004563041731574,0,0,
2227,Chorea and related disorders,"Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham's chorea is the most common form of childhood chorea, whereas Huntington's disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.",anxiety;ballism;chorea/ep [Epidemiology];chorea/et [Etiology];chorea/si [Side Effect];chorea minor;choreoathetosis;disease course;dysphagia/si [Side Effect];dystonia/si [Side Effect];gait disorder/si [Side Effect];hemiballism;human;Huntington chorea/ep [Epidemiology];involuntary movement;neurotoxicity/si [Side Effect];rash/si [Side Effect];restlessness;review;skin discoloration/si [Side Effect];sleep;stress;subthalamic nucleus;tardive dyskinesia/si [Side Effect];Wilson disease/dt [Drug Therapy];amantadine/dt [Drug Therapy];amphetamine/ae [Adverse Drug Reaction];anticonvulsive agent/ae [Adverse Drug Reaction];atypical antipsychotic agent/dt [Drug Therapy];benzodiazepine derivative/ae [Adverse Drug Reaction];carbamazepine/ae [Adverse Drug Reaction];clozapine/dt [Drug Therapy];cocaine/ae [Adverse Drug Reaction];dopamine receptor blocking agent/ae [Adverse Drug Reaction];dopamine receptor stimulating agent/ae [Adverse Drug Reaction];gabapentin/ae [Adverse Drug Reaction];haloperidol/ae [Adverse Drug Reaction];haloperidol/dt [Drug Therapy];levodopa/ae [Adverse Drug Reaction];methylphenidate/ae [Adverse Drug Reaction];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];olanzapine/dt [Drug Therapy];oral contraceptive agent/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];phenytoin/ae [Adverse Drug Reaction];quetiapine/dt [Drug Therapy];reserpine/ae [Adverse Drug Reaction];riluzole/dt [Drug Therapy];risperidone/dt [Drug Therapy];serotonin uptake inhibitor/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];ubiquinone/dt [Drug Therapy];unindexed drug;valproic acid/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Bhidayasiri, R.;Truong, D. D.",2004,September,http://dx.doi.org/10.1136/pgmj.2004.019356,0,0,
2228,Severe hepatitis during Wilson's disease. [French],,adult;case report;conference paper;corticosteroid therapy;disease severity;female;hepatic encephalopathy/co [Complication];human;laboratory test;liver biopsy;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver transplantation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];adenosine triphosphatase;ceruloplasmin;chelating agent/do [Drug Dose];chelating agent/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Duvoux, C.",2004,May,,0,0,
2229,Thrombocytopenia as a side effect of trientene in the treatment of neurological symptoms of Wilson's disease. [German],"Until recently the chelating agent D-penicillamine has been considered the first-choice treatment of neurologic Wilson's disease. A newer approach is the treatment with alternative chelators, such as triethylene tetramine dihydrochloride (Trientene). No significant side effects of this regimen have been published so far. Here we report a 28-year old patient with neurological manifestation of the disease. He was medicated with Trientene and developed a transient thrombocytopenia during the course of the treatment, which was successfully treated by a reduction of Trientene dosage. Without controlled randomised studies, no specific recommendation for the treatment of neurologic Wilson's disease is available. Discussing the present case report, we review current treatment strategies in patients suffering from neurological symptoms in Wilson's disease.",adult;article;case report;clinical feature;diagnostic imaging;drug dose reduction;drug effect;drug efficacy;drug response;human;image analysis;male;neurologic disease/dt [Drug Therapy];nuclear magnetic resonance imaging;symptom;thrombocytopenia/di [Diagnosis];thrombocytopenia/si [Side Effect];treatment outcome;Wilson disease/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/cb [Drug Combination];chelating agent/do [Drug Dose];chelating agent/dt [Drug Therapy];metalkaptase;metoprolol/do [Drug Dose];metoprolol/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];tetrathiomolybdate ammonium/do [Drug Dose];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/do [Drug Dose];trientine/dt [Drug Therapy];univar;zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy],"Sabolek, M.;Weidanbach, M.;Storch, A.;Kraft, E.",2004,June,http://dx.doi.org/10.1055/s-2003-814982,0,0,
2230,Inherited copper toxicosis with emphasis on copper toxicosis in Bedlington terriers,"Canine copper toxicosis is an important inherited disease in Bedlington terriers, because of its high prevalence rate and similarity to human copper storage disease. It can lead to chronic liver disease and occasional haemolytic anaemia due to impaired copper excretion. The responsible gene for copper toxicosis in Bedlington terriers has been recently identified and was found not to be related to human Wilson's disease gene ATP7B. Although our understanding of copper metabolism in mammals has improved through genetic molecular technology, the diversity of gene mutation related to copper metabolism in animals will help identify the responsible genes for non-Wilsonian copper toxicoses in human. This review paper discusses our knowledge of normal copper metabolism and the pathogenesis, molecular genetics and current research into copper toxicosis in Bedlington terriers, other animals and humans. © 2004 Elsevier GmbH. All rights reserved.",atp7b;Autosomal recessive inheritance;Bedlington terriers;Canine copper toxicosis;CFA10q26;Copper metabolism;murr1;Wilson's disease;chronic liver disease;dog;excretion;gene identification;gene mutation;gene technology;hemolytic anemia;intoxication/di [Diagnosis];intoxication/dt [Drug Therapy];intoxication/et [Etiology];intoxication/th [Therapy];mammal;medical research;molecular genetics;nonhuman;pathogenesis;review;storage disease;alpha tocopherol;antiinflammatory agent;copper/to [Drug Toxicity];gluconate zinc/cm [Drug Comparison];gluconate zinc/dt [Drug Therapy];gluconate zinc/to [Drug Toxicity];gluconate zinc/po [Oral Drug Administration];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/pd [Pharmacology];pyridoxine;trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity];trientine/pd [Pharmacology];zinc/cm [Drug Comparison];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity];zinc/po [Oral Drug Administration];zinc acetate/dt [Drug Therapy];zinc acetate/to [Drug Toxicity];zinc acetate/po [Oral Drug Administration];zinc acetate/pd [Pharmacology],"Hyun, C.;Filippich, L. J.",2004,May,http://dx.doi.org/10.1016/j.jeas.2004.01.003,0,0,
2231,Metals in our minds: Therapeutic implications for neurodegenerative disorders,"Background Abnormal interactions of copper or iron in the brain with metal-binding proteins (such as amyloid-beta peptide [Abeta] or neuromelanin) that lead to oxidative stress have emerged as important potential mechanisms in brain ageing and neurodegenerative disorders. Although a controlled study of desferrioxamine in Alzheimer's disease(AD) had some promising results, concerns about toxicity and brain delivery have limited trials of traditional chelators. The therapeutic significance of metal dysregulation in neurodegenerative disorders has remained difficult to test. Recent developments Clioquinol was identified as a prototype metal-protein-attenuating compound (MPAC). In a blinded and controlled 9 week study of a mouse model of AD, oral clioquinol decreased brain Abeta by 49% without systemic toxicity. The concentrations of copper and zinc in the brain rose by about 15% in mice treated with clioquinol. Two other studies in mice showed that the raising of brain copper concentrations through diet or genetics could lower amyloid load and increase survival. A recent placebo-controlled trial in 36 patients with AD showed that clioquinol (250-750 mg daily) reduced plasma concentrations of Abeta<inf>1-42</inf>, raised plasma concentrations of zinc, and - in a subset with moderate dementia - slowed cognitive decline over 24 weeks. Two recent experiments also showed the neuroprotective effects of iron chelation in a mouse model of Parkinson's disease. Where next? The experimental and transgenic-animal studies of metal-protein interactions are convincing but do not provide conclusive answers either about causality or whether this strategy will protect against neurodegeneration in human beings. The finding that clioquinol could modulate plasma concentrations of amyloid and cognition in patients with AD needs to be interpreted cautiously, but is an important first step. Clioquinol was withdrawn because of concerns of its association with subacute myelo-optic neuropathy in Japan; therefore, any additional studies with this drug will likely be small and closely monitored proof-of-concept studies. The development of optimal second-generation MPACs is a desirable goal and may permit greater insights into the significance of metal-protein interactions across several neurodegenerative disorders.",Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/et [Etiology];brain hemorrhage/et [Etiology];cataract/et [Etiology];coronary artery atherosclerosis/et [Etiology];Creutzfeldt Jakob disease/et [Etiology];diffuse Lewy body disease/et [Etiology];Down syndrome/et [Etiology];drug brain level;Fahr disease/et [Etiology];Friedreich ataxia/et [Etiology];hemochromatosis/et [Etiology];human;Huntington chorea/et [Etiology];multiple sclerosis/et [Etiology];nerve degeneration/et [Etiology];neuropathology;Parkinson disease/et [Etiology];priority journal;progressive supranuclear palsy/et [Etiology];review;tardive dyskinesia/et [Etiology];Wilson disease/et [Etiology];zinc blood level;amyloid beta protein/ec [Endogenous Compound];clioquinol/cr [Drug Concentration];clioquinol/pd [Pharmacology];copper;iron;neuromelanin/ec [Endogenous Compound];zinc,"Doraiswamy, P. M.;Finefrock, A. E.",2004,01 Jul,http://dx.doi.org/10.1016/S1474-4422%2804%2900809-9,0,0,
2232,Hereditary liver diseases. [German],"In recent years the identification and characterization of gene defects underlying hereditary liver diseases lead to a better understanding of their pathogenesis. Heditary hemochromatosis, Wilson's disease and alpha1-antitrypsin deficiency are the most common hereditary liver diseases. While gene defects and disease manifestation may correlate, genetic testing is generally not contributing to diagnosis. This review summarizes the clinical manifestations, diagnosis and therapy of the most frequent hereditary liver diseases: hereditary hemochromatosis, Wilson's disease and alpha1-antitrypsin deficiency.",alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/dt [Drug Therapy];alpha 1 antitrypsin deficiency/ep [Epidemiology];alpha 1 antitrypsin deficiency/et [Etiology];clinical examination;clinical feature;correlation analysis;drug indication;epidemiological data;gene mutation;genetic analysis;genetic disorder/di [Diagnosis];genetic disorder/dt [Drug Therapy];genetic disorder/ep [Epidemiology];genetic disorder/et [Etiology];Germany;hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/ep [Epidemiology];hemochromatosis/et [Etiology];human;laboratory diagnosis;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/ep [Epidemiology];liver disease/et [Etiology];liver transplantation;medical literature;pathogenesis;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];alpha 1 antitrypsin/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Spangenberg, H. C.;Rosler, K.;Blum, H. E.",2004,,,0,0,
2233,Wilson disease and hepatocellular carcinoma,,Carcinogenesis;Copper;Hepatocellular carcinoma;Wilson disease;alanine aminotransferase blood level;cancer screening;cell proliferation;chronic hepatitis/co [Complication];clinical feature;disease association;disease classification;disease predisposition;editorial;human;life expectancy;liver cell;liver cell carcinoma/di [Diagnosis];liver cell carcinoma/et [Etiology];liver cell damage;liver cirrhosis/co [Complication];liver dysfunction;liver failure/co [Complication];nonhuman;risk factor;Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];hepatitis B antibody/ec [Endogenous Compound];hepatitis B surface antigen/ec [Endogenous Compound];hepatitis C antibody/ec [Endogenous Compound];penicillamine,"Harada, M.",2004,November,http://dx.doi.org/10.2169/internalmedicine.43.1012,0,0,
2234,Inhibition of key cytokines by tetrathiomolybdate in the bleomycin model of pulmonary fibrosis,"Tetrathiomolybdate is an anticopper drug with a unique mechanism of action. Tetrathiomolybdate complexes copper to protein and itself, rendering the copper unavailable for cellular uptake. It was originally developed for Wilson's disease, and is now being developed as an antiangiogenic agent for the treatment of cancer. Many angiogenic cytokines require normal levels of copper, and lowered copper levels reduce cytokine signaling while cellular copper requirements are met. Cytokines of fibrosis and inflammation may be similarly copper dependent, since tetrathiomolybdate inhibits bleomycin induced pulmonary inflammation and fibrosis. The basis for this inhibition was evaluated here by examination of tetrathiomolybdate effects on cytokines in lung pathophysiologically important in the bleomycin mouse model of pulmonary damage. Results in mice injected endotracheally with bleomycin confirmed that tetrathiomolybdate therapy was effective in reducing fibrosis. This effect was associated with significant inhibition of bleomycin-induced tumor necrosis factor alpha and transforming growth factor beta expression in lung homogenates. These effects were shown to be independent of one another. This indicates that tetrathiomolybdate therapy can be effective even when fibrosis is at a more chronic stage, wherein inflammatory cytokines are playing a diminishing role. The inhibition of tumor necrosis factor alpha suggests that diseases of tumor necrosis factor alpha overexpression are also potential targets of tetrathiomolybdate therapy. © 2004 Elsevier Inc. All rights reserved.",Bleomycin;Copper;Cytokines;Pulmonary fibrosis;Tetrathiomolybdate;animal experiment;animal model;animal tissue;article;controlled study;drug effect;drug efficacy;female;lung fibrosis/dt [Drug Therapy];lung homogenate;lung injury/dt [Drug Therapy];mouse;nonhuman;pathophysiology;protein expression;cytokine/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/ig [Intragastric Drug Administration];tetrathiomolybdic acid/pd [Pharmacology];transforming growth factor beta/ec [Endogenous Compound];tumor necrosis factor alpha/ec [Endogenous Compound],"Brewer, G. J.;Dick, R.;Ullenbruch, M. R.;Jin, H.;Phan, S. H.",2004,December,http://dx.doi.org/10.1016/j.jinorgbio.2004.10.006,0,0,
2235,"Iron, brain ageing and neurodegenerative disorders","There is increasing evidence that iron is involved in the mechanisms that underlie many neurodegenerative diseases. Conditions such as neuroferritinopathy and Friedreich ataxia are associated with mutations in genes that encode proteins that are involved in iron metabolism, and as the brain ages, iron accumulates in regions that are affected by Alzheimer's disease and Parkinson's disease. High concentrations of reactive iron can increase oxidative-stress induced neuronal vulnerability, and iron accumulation might increase the toxicity of environmental or endogenous toxins. By studying the accumulation and cellular distribution of iron during ageing, we should be able to increase our understanding of these neurodegenerative disorders and develop new therapeutic strategies.","aging;Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];brain;cardiomyopathy/dt [Drug Therapy];degenerative disease/dt [Drug Therapy];degenerative disease/et [Etiology];disease association;dopaminergic nerve cell;Friedreich ataxia;gene mutation;globus pallidus;Hallervorden Spatz disease/cn [Congenital Disorder];human;iron deficiency;iron metabolism;iron overload/cn [Congenital Disorder];locus ceruleus;neurotoxicity/si [Side Effect];nonhuman;nuclear magnetic resonance imaging;oxidative stress;Parkinson disease/dt [Drug Therapy];Parkinson disease/et [Etiology];positron emission tomography;priority journal;putamen;restless legs syndrome/dt [Drug Therapy];restless legs syndrome/et [Etiology];review;substantia nigra;Wilson disease/dt [Drug Therapy];1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine/to [Drug Toxicity];amyloid precursor protein/ec [Endogenous Compound];apotransferrin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];clioquinol/ae [Adverse Drug Reaction];clioquinol/dt [Drug Therapy];curcumin/dt [Drug Therapy];cytochrome c/ec [Endogenous Compound];cytochrome reductase/ec [Endogenous Compound];deferoxamine mesylate/dt [Drug Therapy];deferoxamine mesylate/pk [Pharmacokinetics];deferoxamine mesylate/pd [Pharmacology];dopamine/ec [Endogenous Compound];epigallocatechin gallate/pd [Pharmacology];ferritin/ec [Endogenous Compound];frataxin/ec [Endogenous Compound];heme oxygenase 1/ec [Endogenous Compound];hemosiderin/ec [Endogenous Compound];hepcidin;idebenone/dt [Drug Therapy];iron/ec [Endogenous Compound];lactoferrin/ec [Endogenous Compound];natural resistance associated macrophage protein 2/ec [Endogenous Compound];neuromelanin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];protein/ec [Endogenous Compound];rasagiline/dt [Drug Therapy];transferrin/ec [Endogenous Compound];transferrin receptor/ec [Endogenous Compound];tyrosine 3 monooxygenase/ec [Endogenous Compound];unclassified drug;unindexed drug;vk 28/dt [Drug Therapy];vk 28/pd [Pharmacology]","Zecca, L.;Youdim, M. B. H.;Riederer, P.;Connor, J. R.;Crichton, R. R.",2004,November,http://dx.doi.org/10.1038/nrn1537,0,0,
2236,Wilson's disease with severe neurological manifestations: Response to trientine plus zinc therapy. [Spanish],"In patients with Wilson's disease and neurological manifestations, treatment with D-penicillamine can cause worsening of neurological symptoms, usually in the first few weeks of treatment. Because the neurological damage can be severe and irreversible, the use of D-penicillamine is controversial, and several authors believe that it should be avoided. Studies of the use of ammonium tetrathiomolybdate as an alternative chelating agent for the initial treatment of neurologic Wilson's disease are still in the experimental phase. Published experience on the simultaneous use of trientine, another chelating agent, and zinc, which blocks intestinal absorption of copper, is promising but limited. We present the case of a 17 year-old boy with severe neurologic Wilson's disease that had first presented six years previously. The patient showed a complete recovery after six months of treatment with a combination of trientine and zinc acetate.",adolescent;article;calcium absorption;case report;convalescence;disease exacerbation/si [Side Effect];disease severity;drug contraindication;drug response;human;intestine absorption;male;neurologic disease/si [Side Effect];onset age;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dv [Drug Development];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dv [Drug Development];trientine/cb [Drug Combination];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];zinc/cb [Drug Combination];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Serra, B.;Primo Vera, J.;Garcia, M.;Amoros, I.;Arago, M.;Merino, C.",2004,May,http://dx.doi.org/10.1157/13060690,0,0,
2237,Movement disorders,"The movement disorders Parkinson's disease, essential tremor, Wilson's disease, Huntington's disease, drug-induced movement disorders, and Tourette's syndrome are addressed in this article. Definition, epidemiology, etiology, clinical manifestations, diagnosis, and treatment are discussed.",clinical feature;clinical trial;differential diagnosis;essential tremor/di [Diagnosis];essential tremor/dt [Drug Therapy];essential tremor/ep [Epidemiology];essential tremor/et [Etiology];essential tremor/su [Surgery];gastrointestinal toxicity/si [Side Effect];Gilles de la Tourette syndrome/di [Diagnosis];Gilles de la Tourette syndrome/dt [Drug Therapy];Gilles de la Tourette syndrome/ep [Epidemiology];Gilles de la Tourette syndrome/et [Etiology];human;Huntington chorea/di [Diagnosis];Huntington chorea/dt [Drug Therapy];Huntington chorea/ep [Epidemiology];Huntington chorea/et [Etiology];motor dysfunction/di [Diagnosis];motor dysfunction/dt [Drug Therapy];motor dysfunction/ep [Epidemiology];motor dysfunction/et [Etiology];neuropathology;neurotoxicity/si [Side Effect];Parkinson disease/di [Diagnosis];Parkinson disease/dt [Drug Therapy];Parkinson disease/ep [Epidemiology];Parkinson disease/et [Etiology];pathophysiology;priority journal;review;sexual dysfunction/si [Side Effect];side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];alprazolam/ct [Clinical Trial];alprazolam/do [Drug Dose];alprazolam/dt [Drug Therapy];alprazolam/pd [Pharmacology];amantadine/ct [Clinical Trial];amantadine/do [Drug Dose];amantadine/dt [Drug Therapy];amantadine/pd [Pharmacology];antidepressant agent/ae [Adverse Drug Reaction];antidepressant agent/ct [Clinical Trial];antidepressant agent/do [Drug Dose];antidepressant agent/dt [Drug Therapy];antidepressant agent/pd [Pharmacology];antiparkinson agent/ct [Clinical Trial];antiparkinson agent/do [Drug Dose];antiparkinson agent/dt [Drug Therapy];antiparkinson agent/pd [Pharmacology];benzatropine/ct [Clinical Trial];benzatropine/do [Drug Dose];benzatropine/dt [Drug Therapy];benzatropine/pd [Pharmacology];botulinum toxin A/ct [Clinical Trial];botulinum toxin A/do [Drug Dose];botulinum toxin A/dt [Drug Therapy];botulinum toxin A/pd [Pharmacology];bromocriptine/ct [Clinical Trial];bromocriptine/do [Drug Dose];bromocriptine/dt [Drug Therapy];bromocriptine/pd [Pharmacology];carbidopa/ct [Clinical Trial];carbidopa/do [Drug Dose];carbidopa/dt [Drug Therapy];carbidopa/pd [Pharmacology];catechol methyltransferase inhibitor/ct [Clinical Trial];catechol methyltransferase inhibitor/do [Drug Dose];catechol methyltransferase inhibitor/dt [Drug Therapy];catechol methyltransferase inhibitor/pd [Pharmacology];cholinergic receptor blocking agent/ct [Clinical Trial];cholinergic receptor blocking agent/do [Drug Dose];cholinergic receptor blocking agent/dt [Drug Therapy];cholinergic receptor blocking agent/pd [Pharmacology];clonidine/ct [Clinical Trial];clonidine/do [Drug Dose];clonidine/dt [Drug Therapy];clonidine/pd [Pharmacology];clozapine/ct [Clinical Trial];clozapine/do [Drug Dose];clozapine/dt [Drug Therapy];clozapine/pd [Pharmacology];dopamine receptor stimulating agent/ct [Clinical Trial];dopamine receptor stimulating agent/do [Drug Dose];dopamine receptor stimulating agent/dt [Drug Therapy];dopamine receptor stimulating agent/pd [Pharmacology];gabapentin/ct [Clinical Trial];gabapentin/do [Drug Dose];gabapentin/dt [Drug Therapy];gabapentin/pd [Pharmacology];levodopa/ct [Clinical Trial];levodopa/do [Drug Dose];levodopa/dt [Drug Therapy];levodopa/pd [Pharmacology];nimodipine/ct [Clinical Trial];nimodipine/do [Drug Dose];nimodipine/dt [Drug Therapy];nimodipine/pd [Pharmacology];penicillamine/ct [Clinical Trial];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pergolide/ct [Clinical Trial];pergolide/do [Drug Dose];pergolide/dt [Drug Therapy];pergolide/pd [Pharmacology];pramipexole/ct [Clinical Trial];pramipexole/do [Drug Dose];pramipexole/dt [Drug Therapy];pramipexole/pd [Pharmacology];primidone/ct [Clinical Trial];primidone/dt [Drug Therapy];primidone/pd [Pharmacology];propranolol/ct [Clinical Trial];propranolol/do [Drug Dose];propranolol/dt [Drug Therapy];propranolol/pd [Pharmacology];ropinirole/ct [Clinical Trial];ropinirole/do [Drug Dose];ropinirole/dt [Drug Therapy];ropinirole/pd [Pharmacology];selegiline/ct [Clinical Trial];selegiline/do [Drug Dose];selegiline/dt [Drug Therapy];selegiline/pd [Pharmacology];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];theophylline/ct [Clinical Trial];theophylline/do [Drug Dose];theophylline/dt [Drug Therapy];theophylline/pd [Pharmacology];topiramate/ct [Clinical Trial];topiramate/dv [Drug Development];topiramate/dt [Drug Therapy];topiramate/pd [Pharmacology];trientine/ct [Clinical Trial];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];trihexyphenidyl/ct [Clinical Trial];trihexyphenidyl/do [Drug Dose];trihexyphenidyl/dt [Drug Therapy];trihexyphenidyl/pd [Pharmacology];unindexed drug;zinc acetate/ct [Clinical Trial];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy];zinc acetate/pd [Pharmacology],"Minagar, A.;Kelley, R. E.",2004,March,http://dx.doi.org/10.1016/S0095-4543%2803%2900119-2,0,0,
2238,Successful ECT in a Patient with a Psychiatric Presentation of Wilson's Disease [5],,adult;anesthesia induction;case report;catatonic schizophrenia/di [Diagnosis];catatonic schizophrenia/th [Therapy];clinical feature;delusion;depression/di [Diagnosis];depression/th [Therapy];electroconvulsive therapy;hallucination;human;letter;male;medical examination;neuroleptic malignant syndrome/si [Side Effect];paranoid schizophrenia/di [Diagnosis];paranoid schizophrenia/dt [Drug Therapy];psychiatric diagnosis;treatment outcome;Wilson disease/di [Diagnosis];amitriptyline/dt [Drug Therapy];haloperidol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];risperidone/dt [Drug Therapy];thioridazine/ae [Adverse Drug Reaction];thioridazine/dt [Drug Therapy],"Rodrigues, A. C. T.;Dalgalarrondo, P.;Banzato, C. E. M.",2004,,http://dx.doi.org/10.1097/00124509-200403000-00017,0,0,
2239,Serial diffusion-weighted MRI in a case of Wilson's disease with acute onset hemichorea [6],,adolescent;bilirubin blood level;brain disease;case report;cerebrovascular disease;chorea;diffusion coefficient;diffusion weighted imaging;echography;female;follow up;human;involuntary movement;lactic acidosis;letter;mitochondrial myopathy;mitochondrion;oxidative phosphorylation;priority journal;statistical significance;stroke;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];reactive oxygen metabolite,"Kawamura, N.;Ohyagi, Y.;Kawajiri, M.;Yoshiura, T.;Mihara, F.;Furuya, H.;Kira, J. I.",2004,November,http://dx.doi.org/10.1007/s00415-004-0555-4,0,0,
2240,Gastroenterology and hepatology quiz (H-Q26). [Romanian],,adult;case report;digestive tract endoscopy;esophagus biopsy;fatty liver;gastroesophageal reflux;hepatitis B/di [Diagnosis];hepatitis B/dt [Drug Therapy];histopathology;human;liver cirrhosis/co [Complication];liver cirrhosis/di [Diagnosis];liver hemosiderosis;non insulin dependent diabetes mellitus;note;self examination;upper gastrointestinal tract;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin;copper;famotidine;hepatitis B surface antigen;hepatitis B(e) antigen;lamivudine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],Anonymous,2004,December,,0,0,
2241,Tetrathiomolybdate protects against liver injury from acetaminophen in mice,"Acetaminophen toxicity has become a leading cause of both accidental and intentional poisoning, and is now the most common cause of acute liver failure in the United States Acetaminophen poisoning is thus a significant burden on the health care system and a cause of considerable morbidity and mortality Tetrathiomolybdate is a fast acting anticopper drug developed for Wilson's disease However, if copper levels are lowered with tetrathiomolybdate, anticancer effects are obtained both in animal models and human patients Inhibition of angiogenic cytokines by tetrathiomolybdate is the hypothesized mechanism Tetrathiomolybdate has also proven to be effective against organ damage in the bleomycin mouse model of pulmonary damage, and in concanavalin A and carbon tetrachloride models of liver damage Again, the hypothesized mechanism is cytokine inhibition, in this case inhibition of profibrotic and proinflammatory cytokines In the present work in mice, we show that tetrathiomolybdate protects against liver damage from acetaminophen Further, we show that the drug can be started after acetaminophen administration, and still be effective, indicating a possible role in treating human acetaminophen poisoning.",Acetaminophen;Amino leucine transaminase;Ceruloplasmin;Copper;Hepatotoxicity;Tetrathiomolybdate;animal model;antineoplastic activity;article;controlled study;drug efficacy;drug intoxication/et [Etiology];drug mechanism;female;liver failure/et [Etiology];liver injury/et [Etiology];liver protection;liver toxicity/et [Etiology];lung injury/et [Etiology];mouse;nonhuman;Wilson disease/et [Etiology];bleomycin/to [Drug Toxicity];carbon tetrachloride/to [Drug Toxicity];concanavalin A/to [Drug Toxicity];copper/to [Drug Toxicity];cytokine;paracetamol/to [Drug Toxicity];paracetamol/po [Oral Drug Administration];tetrathiomolybdic acid/ip [Intraperitoneal Drug Administration];tetrathiomolybdic acid/po [Oral Drug Administration];tetrathiomolybdic acid/pd [Pharmacology],"Ma, S.;Hou, G.;Dick, R.;Brewer, G. J.",2004,,,0,0,
2242,Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration,"Background: Copper deficiency in ruminants is known to cause an ataxic myelopathy. Copper deficiency as a cause of progressive myelopathy in adults is underrecognized. Objective: To describe the clinical, biochemical, electrophysiologic, and imaging characteristics in 13 patients with myelopathy associated with copper deficiency. Methods: The records of patients with a copper deficiency-associated myelopathy were reviewed. Clinical characteristics, laboratory investigations, and responses to therapeutic intervention were summarized. Results: Thirteen such patients were found, 11 of them in a 15-month period. All patients presented with prominent gait difficulty, reflecting a sensory ataxia due to dorsal column dysfunction and lower limb spasticity. All patients had polyneuropathy. A high or high-normal serum zinc level was seen in 7 of the 11 patients for whom this information was available. Somatosensory evoked potential studies done in eight patients showed impaired conduction in central proprioceptive pathways. Dorsal column signal change on spine MRI was present in three patients. An initial clue to the diagnosis was a very low ceruloplasmin level; further tests of copper metabolism excluded Wilson disease. The cause remained unexplained in most patients. Oral copper supplementation restored normal or near-normal copper levels in 7 of the 12 patients in whom adequate follow-up data were available; parenteral supplementation restored normal level in 3 further patients. Copper supplementation prevented further neurologic deterioration, but the degree of actual improvement was variable. Conclusions: Unrecognized copper deficiency appears to be a common cause of idiopathic myelopathy in adults. The clinical picture bears striking similarities to the syndrome of subacute combined degeneration associated with vitamin B<inf>12</inf> deficiency. Early recognition and copper supplementation may prevent neurologic deterioration.",adult;aged;article;ataxia;ceruloplasmin blood level;clinical article;clinical feature;copper deficiency/di [Diagnosis];copper deficiency/dt [Drug Therapy];cyanocobalamin deficiency;disease association;evoked somatosensory response;female;gait disorder;human;human tissue;leg;male;nerve conduction;nerve degeneration;nuclear magnetic resonance imaging;polyneuropathy;priority journal;proprioception;spasticity;spinal cord disease/di [Diagnosis];spinal cord disease/dt [Drug Therapy];Wilson disease;zinc blood level;ceruloplasmin/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/po [Oral Drug Administration],"Kumar, N.;Gross Jr, J. B.;Ahlskog, J. E.",2004,13 Jul,,0,0,
2243,The other mutation is found: Follow-up of an exceptional family with Wilson disease [6],,chelation therapy;copper metabolism;family;follow up;gene mutation;genotype phenotype correlation;haplotype;heterozygote;homozygosity;human;letter;liver transplantation;missense mutation;neurologic disease;priority journal;side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Firneisz, G.;Szonyi, L.;Ferenci, P.;Willheim, C.;Horvath, A.;Folhoffer, A.;Tulassay, Z.;Szalay, F.",2004,December,http://dx.doi.org/10.1111/j.1572-0241.2004.41389_8.x,0,0,
2244,Epilepsy and Wilson's disease: Case report and literature review. [Italian],"We describe the case of a 26 years old patient, with neuro-psychiatric onset of Wilson's disease, who developed severe generalized dystonia, dysphagia and dysphonia, two weeks after introducing Penicillamine treatment. Brain MRI showed extensive damage of cerebral white matter and cortex in temporal lobes, basal ganglia, thalamus and brainsteam. Despite of treatment was shifted to Trientine and Zinc Acetate, there was not clinical improvement and a month later the patient presented a status epilepticus. In addition a new MRI showed an important extension of temporal lesions.",Dystonia;Epilepsy;Penicillamine;Seizures;Status epilepticus;Trientine;Wilson's disease;adult;basal ganglion;brain injury;brain stem;case report;clinical feature;conference paper;disease course;dysphagia/dt [Drug Therapy];dysphonia/dt [Drug Therapy];dystonia/dt [Drug Therapy];epilepsy/dt [Drug Therapy];epileptic state;human;male;nuclear magnetic resonance imaging;temporal cortex;thalamus;white matter;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Chiesa, V.;Secchi, M.;Caverni, L.;Zuin, M.;Meda, F.;Canevini, M. P.",2004,July/December,,0,0,
2245,Persistence of Elevated Aminotransferases in Wilson's Disease Despite Adequate Therapy [2],,aminotransferase blood level;child;clinical feature;hepatomegaly;human;letter;liver failure/su [Surgery];liver transplantation;major clinical study;patient compliance;priority journal;retrospective study;treatment outcome;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aminotransferase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Iorio, R.;D'Ambrosi, M.;Marcellini, M.;Barbera, C.;Maggiore, G.;Zancan, L.;Giacchino, R.;Vajro, P.;Marazzi, M. G.;Francavilla, R.;Michielutti, F.;Resti, M.;Frediani, T.;Pastore, M.;Vegnente, A.",2004,April,,0,0,
2246,"Basal ganglia: Anatomy, pathology, and imaging characteristics","Several cases of bilateral basal ganglia lesions seen in magnetic resonance imaging initiated a review of the anatomy, pathology, and differential diagnoses of this region. There are a variety of disease entities that present as symmetrical basal ganglia abnormalities. Although these findings may not indicate a specific diagnosis, knowledge of the characteristics of diseases that affect this area can limit the differential considerations. Clinical information is often essential for narrowing the possible pathology that can be found here. The purpose of this article is to review the anatomy of the basal ganglia, the pathologies, clinical histories, and imaging characteristics that can cause bilateral basal ganglia lesions.",basal ganglion;brain calcification/di [Diagnosis];brain calcification/et [Etiology];brain calcification/si [Side Effect];brain hypoxia/di [Diagnosis];brain hypoxia/et [Etiology];brain infarction/di [Diagnosis];brain ischemia/di [Diagnosis];brain ischemia/et [Etiology];carbon monoxide intoxication/di [Diagnosis];clinical feature;computer assisted tomography;Creutzfeldt Jakob disease/di [Diagnosis];Creutzfeldt Jakob disease/et [Etiology];differential diagnosis;extrapyramidal syndrome/co [Complication];extrapyramidal syndrome/di [Diagnosis];extrapyramidal syndrome/et [Etiology];extrapyramidal syndrome/si [Side Effect];Hallervorden Spatz disease/di [Diagnosis];Hallervorden Spatz disease/et [Etiology];human;image analysis;Leigh disease/di [Diagnosis];Leigh disease/et [Etiology];neuroanatomy;neurofibromatosis/di [Diagnosis];neurofibromatosis/et [Etiology];nuclear magnetic resonance imaging;pathological anatomy;review;striatonigral degeneration/di [Diagnosis];striatonigral degeneration/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];carbon monoxide/to [Drug Toxicity];methanol/to [Drug Toxicity];methotrexate/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Anderson, J. C.;Costantino, M. M.;Stratford, T.",2004,January/February,http://dx.doi.org/10.1016/j.cpradiol.2003.09.004,0,0,
2247,Neuropsychiatric Presentation in a Child with Wilson's Disease,"Wilson Disease (WD) an inherited copper metabolism disorder can affect several systems. Although hepatic presentation predominates in early childhood, neuropsychiatric features are evident in adolescent age group. Many of psychiatric symptoms can be observed in patients with WD such as depressive mood, personality changes, or schizophrenia. Misdiagnosis and inappropriate treatment are not uncommon when psychiatric symptoms are the presenting complaints. In this article we present a 14 year-old boy with WD who had received antidepressive treatment because of his initial depressive symptoms. Diagnosis of WD was confirmed by increased 24-hour urinary copper excretion and Kayser-Fleischer ring in cornea. In patients with WD, initial depressive mood suggesting a psychiatric disorder may lead to misdiagnosis.",Childhood;Depression;Neuropsychiatric;Wilson's disease;adolescent;age distribution;article;case report;clinical feature;copper metabolism;depression/di [Diagnosis];depression/dt [Drug Therapy];diagnostic error;disease course;dystonia/dt [Drug Therapy];human;human tissue;inheritance;liver biopsy;male;mood disorder;neurologic examination;neuropsychiatry;nuclear magnetic resonance imaging;ophthalmoscopy;personality disorder;physical examination;schizophrenia;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];antidepressant agent/dt [Drug Therapy];copper/ec [Endogenous Compound];imipramine/dt [Drug Therapy];levodopa/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Odemis, E.;Aynaci, F. M.;Kandil, S. T.;Yontem, T.;Topcul, M.",2003,September,,0,0,
2248,Wilson Disease,,autosomal recessive disorder;bile flow;chelation therapy;chromosome 13;clinical feature;copper metabolism;diagnostic test;diet therapy;gene location;genetic screening;human;liver transplantation;living donor;pathogenesis;pathophysiology;prevalence;priority journal;protein function;review;screening test;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];zinc acetate/po [Oral Drug Administration],"Gitlin, J. D.",2003,December,http://dx.doi.org/10.1053/j.gastro.2003.05.010,0,0,
2249,DNA linkage based diagnosis of Wilson disease in asymptomatic siblings,"Background & objectives: Wilson disease (WD) is an autosomal recessive disorder caused by defects in ATP7B gene located in chromosome 13q14, and manifested as hepatolenticular degeneration as a result of accumulation of copper. No information on the mutation in the ATP7B gene and haplotypes using linked markers is available for WD patients in India. Hence, the present study was undertaken to identify, by a PCR-based molecular diagnostic test, presymptomatic siblings of WD affected individuals in families with multiple offspring. Methods: Genomic DNA was prepared from the peripheral blood of the patients, siblings and his/her first degree relatives. The repeat-markers flanking WD locus were amplified by PCR using fluorescent labeled primers. Amplified DNA fragments were analyzed by polyacrylamide gel electrophoresis in ABI 377 DNA sequencing system. Genotypes of the samples were determined using Genescan software. Haplotypes were determined based on segregation of the alleles in the families under study. Results: Among 15 WD affected families with multiple children, 4 cases were identified where younger siblings shared same genotype as the patient at all three markers analyzed. Further, eight different haplotypes were detected in the four patients. Interpretation & conclusion: The siblings of the WD patients carrying the same genotype at the markers linked to WD locus were presymptomatically diagnosed individuals. Presence of eight different haplotypes in the four patients suggested mutational heterogeneity at the WD locus. The test helps clinicians for therapeutic intervention in suspect WD cases by copper chelating agents prior to manifestation of overt clinical symptoms.",atp7b;Genotype;Haplotype;Microsatellite;Wilson disease;adolescent;adult;allele;article;child;computer program;diagnostic procedure;dinucleotide repeat;DNA flanking region;DNA sequence;female;fluorescence analysis;gene amplification;gene locus;gene mutation;gene segregation;genetic heterogeneity;genetic marker;human;linkage analysis;major clinical study;male;parent;polyacrylamide gel electrophoresis;polymerase chain reaction;relative;segregation analysis;sequence analysis;sibling;symptom;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];DNA fragment/ec [Endogenous Compound];genomic DNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Gupta, A.;Neogi, R.;Mukherjea, M.;Mukhopadhyay, A.;Roychoudhury, S.;Senapati, A.;Gangopadhyay, P. K.;Ray, K.",2003,November,,0,0,
2250,Quetiapine for mania with Wilson's disease [4],,adolescent;autosomal recessive disorder;case report;ceruloplasmin blood level;copper blood level;dystonia;erotomania;extrapyramidal symptom/si [Side Effect];gait disorder;grandiose delusion;human;irritability;letter;male;mania/dt [Drug Therapy];mood disorder;restlessness;Wilson disease;atypical antipsychotic agent/ae [Adverse Drug Reaction];atypical antipsychotic agent/dt [Drug Therapy];clozapine/dt [Drug Therapy];lithium/do [Drug Dose];lithium/dt [Drug Therapy];penicillamine/do [Drug Dose];quetiapine/ae [Adverse Drug Reaction];quetiapine/dt [Drug Therapy],"Kulaksizoglu, I. B.;Polat, A.",2003,September/October,http://dx.doi.org/10.1176/appi.psy.44.5.438,0,0,
2251,A practice guideline on Wilson disease,,aplastic anemia/si [Side Effect];chemical analysis;clinical feature;diagnostic approach route;diet therapy;differential diagnosis;dose response;drug absorption;drug binding;drug bioavailability;drug formulation;drug mechanism;drug screening;elastosis/si [Side Effect];fever/si [Side Effect];food drug interaction;gastritis/si [Side Effect];genetic analysis;human;human tissue;immunopathology/si [Side Effect];leukopenia/si [Side Effect];liver biopsy;liver toxicity/si [Side Effect];liver transplantation;lupus vulgaris/si [Side Effect];nephrotic syndrome/si [Side Effect];neutropenia/si [Side Effect];pancreatitis/si [Side Effect];pathogenesis;practice guideline;priority journal;proteinuria/si [Side Effect];rash/si [Side Effect];retinitis/si [Side Effect];review;side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];skin disease/si [Side Effect];thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];zinc metabolism;alpha tocopherol/dt [Drug Therapy];copper/ec [Endogenous Compound];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/it [Drug Interaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/do [Drug Dose];trientine/it [Drug Interaction];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];trientine/pr [Pharmaceutics];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Roberts, E. A.;Schilsky, M. L.",2003,01 Jun,http://dx.doi.org/10.1053/jhep.2003.50252,0,0,
2252,Liver support - A task for nephrologists? Extracorporeal treatment of a patient with fulminant Wilson crisis,"Background: Patients with Wilson's disease may present with cirrhosis, acute hepatitis or fulminant hepatic failure. Without urgent orthotopic liver transplantation, a fulminant Wilson crisis has a mortality of 100%. We report on an 18-year-old female patient with fulminant hepatic failure due to Wilson crisis. Methods: The molecular adsorbent recirculating system (MARS) was used to eliminate albumin-bound toxins and to bridge waiting until an organ became available. Results: A total of 18 MARS sessions and 4 plasma exchange sessions were performed. Bilirubin levels and hepatic encephalopathy improved under MARS therapy. A total of 75 mg copper was removed until serum copper levels were within the normal range. Copper elimination was measured in 15 MARS treatments, which removed a total of 12.9 mg copper. Four plasma exchange sessions, with a total exchange of 11 liters of plasma, removed 12 mg copper. Urinary copper elimination with penicillamine was 50 mg. Conclusion: MARS was an effective method to stabilize a patient with Wilson crisis, contributed to copper elimination and gained time for liver transplantation. The risk of high-urgency transplantation could be avoided. Liver support was easy in the hands of nephrologists familiar with extracorporeal therapy. Copyright © 2003 S. Karger AG, Basel.",Liver failure;Molecular adsorbent recirculating system;Wilson's disease;adult;albumin dialysis;article;ascites;bilirubin blood level;case report;clinical feature;copper blood level;copper metabolism;disease course;female;gastrointestinal hemorrhage;hemodialysis;hemolysis/th [Therapy];hemoperfusion;hepatic encephalopathy/th [Therapy];human;hypotension;laboratory test;liver;liver biopsy;liver failure/co [Complication];liver failure/th [Therapy];liver transplantation;medical practice;nephrology;organ donor;plasmapheresis;priority journal;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];albumin/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper;penicillamine/dt [Drug Therapy];toxin,"Manz, T.;Ochs, A.;Bisse, E.;Strey, C.;Grotz, W.",2003,,http://dx.doi.org/10.1159/000070695,0,0,
2253,Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice,"Tetrathiomolybdate (TM), a drug developed for the treatment of Wilson's disease, produces an antiangiogenic effect by reducing systemic copper levels. Several angiogenic cytokines appear to depend on normal levels of copper for activity. In both animal tumor models and in cancer patients, TM therapy has proved effective in inhibiting the growth of tumors. We have hypothesized that the activities of fibrotic and inflammatory cytokines are also subject to modulation by the availability of copper in a manner similar to angiogenic cytokines. As a first step in evaluating whether TM plays a therapeutic role in diseases of inflammation and fibrosis, we studied the effects of TM on a murine model of bleomycin-induced pulmonary fibrosis. Oral TM therapy resulted in dose-dependent reduction in serum ceruloplasmin, a surrogate marker of systemic copper levels. Significant decreases in systemic copper levels were associated with marked reduction in lung fibrosis as determined on the basis of histopathologic findings and a biochemical measure of fibrosis. The protection afforded by TM was also reflected in significantly reduced bleomycin-induced body-weight loss. In the next phase of this work, we will seek to determine the mechanisms by which TM brings about this therapeutic benefit.",animal experiment;animal model;article;cancer inhibition;ceruloplasmin blood level;controlled study;copper blood level;dose response;female;fibrosis;histopathology;lung fibrosis/co [Complication];lung fibrosis/dt [Drug Therapy];mouse;nonhuman;weight reduction;angiogenesis inhibitor;bleomycin/to [Drug Toxicity];ceruloplasmin/ec [Endogenous Compound];cytokine;tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration],"Brewer, G. J.;Ullenbruch, M. R.;Dick, R.;Olivarez, L.;Phan, S. H.",2003,01 Mar,http://dx.doi.org/10.1067/mlc.2003.20,0,0,
2254,Investigation of fine-motor disturbances in Wilson's disease,"Patients suffering from Wilson's disease (WD) can be divided into two main subgroups: neurologic and non-neurologic WD. We measured passive and active fine-motor abilities of 37 WD patients and 24 randomly selected volunteers. The measurement was based on a standardized test set in a defined environment for detection of disturbed fine-motor control. The set contains 5 tests comprising rest tremor, postural tremor, target tapping, forefinger tapping and spiral painting, reflecting different aspects of movement disorders. The tests showed significant differences between neurologic WD and volounteers, especially for tasks defining active control. In neurologic WD we found no differences between subgroups whereas for non-neurologic WD we often detected slight movement disorders. The detected movement disorders cam be interpreted as persistent disorders after long-term therapy.",Fine-motor abilities;Movement disorder;VSCOPE system;Wilson's disease;adult;aged;article;body posture;clinical article;controlled study;extrapyramidal symptom;female;human;index finger;long term care;male;motor dysfunction/di [Diagnosis];motor performance;neurologic disease/di [Diagnosis];painting;rest;task performance;tremor;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Hermann, W.;Villmann, T.;Grahmann, F.;Kuhn, H. J.;Wagner, A.",2003,February,http://dx.doi.org/10.1007/s100720300002,0,0,
2255,"Copper lowering therapy with tetrathiomolybdate produces antiangiogenic, anticancer, antifibrotic, and antiinflammatory effects","Tetrathiomolybdate (TM) has been developed to fill an important niche in the initial treatment of Wilson's disease. TM is a potent, fast-acting, non-toxic anticopper agent. Copper appears to be required for activity of many angiogenic factors, which has led to the trial of TM as an antiangiogenic, anticancer drug. Positive results have been obtained in several animal tumor models, and results are encouraging in early clinical work. TM may be a more global antiangiogenic agent than most agents being developed because many angiogenic factors seem to be copper dependent in some manner. The main toxicity of TM is overtreatment bone marrow suppression. Most recently, TM has been shown to inhibit important profibrotic and proinflammatory cytokines, and preclinical status of TM therapy has been positive in lung and liver models of inflammation and fibrosis. © 2004 Elsevier Inc. All rights reserved.",anemia;antiangiogenic activity;antiinflammatory activity;antineoplastic activity;bone marrow suppression;cancer/dt [Drug Therapy];cancer/pc [Prevention];cancer/rt [Radiotherapy];clinical trial;diabetic retinopathy/co [Complication];diabetic retinopathy/dt [Drug Therapy];disease exacerbation/si [Side Effect];drug mechanism;drug potency;drug potentiation;drug synthesis;hepatitis/dt [Drug Therapy];human;leukopenia;liver fibrosis/dt [Drug Therapy];lung fibrosis/dt [Drug Therapy];nonhuman;pneumonia/dt [Drug Therapy];retina macula degeneration/dt [Drug Therapy];retrolental fibroplasia/dt [Drug Therapy];review;treatment outcome;Wilson disease/dt [Drug Therapy];angiogenesis inhibitor/ae [Adverse Drug Reaction];angiogenesis inhibitor/ct [Clinical Trial];angiogenesis inhibitor/cb [Drug Combination];angiogenesis inhibitor/cm [Drug Comparison];angiogenesis inhibitor/dv [Drug Development];angiogenesis inhibitor/it [Drug Interaction];angiogenesis inhibitor/dt [Drug Therapy];angiogenesis inhibitor/to [Drug Toxicity];angiogenesis inhibitor/pd [Pharmacology];angiogenic factor/ec [Endogenous Compound];antifibrotic agent/ae [Adverse Drug Reaction];antifibrotic agent/ct [Clinical Trial];antifibrotic agent/cb [Drug Combination];antifibrotic agent/cm [Drug Comparison];antifibrotic agent/dv [Drug Development];antifibrotic agent/it [Drug Interaction];antifibrotic agent/dt [Drug Therapy];antifibrotic agent/to [Drug Toxicity];antifibrotic agent/pd [Pharmacology];antiinflammatory agent/ae [Adverse Drug Reaction];antiinflammatory agent/ct [Clinical Trial];antiinflammatory agent/cb [Drug Combination];antiinflammatory agent/cm [Drug Comparison];antiinflammatory agent/dv [Drug Development];antiinflammatory agent/it [Drug Interaction];antiinflammatory agent/dt [Drug Therapy];antiinflammatory agent/to [Drug Toxicity];antiinflammatory agent/pd [Pharmacology];antineoplastic agent/ae [Adverse Drug Reaction];antineoplastic agent/ct [Clinical Trial];antineoplastic agent/cb [Drug Combination];antineoplastic agent/cm [Drug Comparison];antineoplastic agent/dv [Drug Development];antineoplastic agent/it [Drug Interaction];antineoplastic agent/dt [Drug Therapy];antineoplastic agent/to [Drug Toxicity];antineoplastic agent/pd [Pharmacology];chelating agent/ae [Adverse Drug Reaction];chelating agent/ct [Clinical Trial];chelating agent/cm [Drug Comparison];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];cytokine/ec [Endogenous Compound];peptide derivative/cb [Drug Combination];peptide derivative/it [Drug Interaction];peptide derivative/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/it [Drug Interaction];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/to [Drug Toxicity];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy],"Brewer, G. J.",2003,December,http://dx.doi.org/10.1016/S1543-1150%2803%2900060-7,0,0,
2256,Diagnosis and treatment of Wilson's disease experience of 38 years therapy in a spezialised out-patients clinic. [German],"Wilson's disease, an hereditary autosomal recessive disorder, is caused by more than 200 different mutations in the gene (locus 13q14.3), encodes a copper-transporting ATPase 7B. Hepatic manifestations became apparent mainly during the first, neurological and psychiatric during the second or third decade of life, seldom later. Genotype-phaenotype correlations are probably. The diagnosis involves laboratory tests (Cu-metabolism), molecular genetics and, if necessary, liver biopsy. Treatment must be continued lifelong, without disruption, also in the pregnancy. Besides D-Penicillamin, which has been the drug of choice for many years, Trientine, zinc and tetrathiomolybdate are used with good success. Monitoring (copper balance, side effects) - at least once or twice yearly - is necessary. Cerebral MRI and FDG-PET seems to be a useful tool in practise for long-term therapy. Continuous care of Wilson patients (38, 10 of among them without hepatic or neurological signs) in a specialised outpatients clinic since 1964 has proven worth. 31 patients consistently treated with D-Penicillamin tolerated the drug well with few side effects. Even marked neurological symptoms improved, some patients became virtually free of symptoms. All patients without clinical signs remained free of symptoms. If intolerance to D-Penicillamin occurs, Trientine and zinc are an effective alternative therapy. Recurrent hepatic decompensations were observed in 2 female patients. One of them eventually required a liver transplant. 19 pregnancies could be carried to full term without complications or fetal damage while taking medication (17 with D-Penicillamin, 2 with Trientine and zinc). Discontinuation of therapy resulted in fatal hepatic failure in one pregnant patient.",chromosome 13q;clinical article;copper metabolism;drug tolerability;female;gene mutation;genotype;human;liver biopsy;liver failure;long term care;molecular genetics;nuclear magnetic resonance imaging;outpatient;phenotype;positron emission tomography;pregnancy;prenatal drug exposure;review;side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Kunath, B.;Reuner, U.",2003,February,http://dx.doi.org/10.1055/s-2003-37060,0,1,
2257,Copper-Lowering Therapy With Tetrathiomolybdate for Cancer and Diseases of Fibrosis and Inflammation,"Angiogenesis is required for tumor growth and is a likely Achilles heel for cancer. However, antiangiogenic agents have been somewhat disappointing in cancer therapy, perhaps because they target a single angiogenic factor, and there is much redundancy in angiogenic systems. Copper is required for high levels of angiogenesis, and many angiogenic factors have a requirement for copper. Thus, anticopper drugs offer the possibility of more global inhibition. Our group has developed tetrathiomolybdate (TM) for the initial treatment of neurologic Wilson's disease. Penicillamine makes about 50% of these patients neurologically worse, and many never recover. Only 2 of 55 (3.6%) patients worsened when treated with TM. Because TM exhibited desirable properties of potency, speed, and safety, we studied it as an antiangiogenic agent. We hypothesize that if copper is lowered to midrange, the cellular requirements for copper are met, but angiogenic cytokine signaling is inhibited. TM has shown strong inhibition of cancer growth in five rodent models, encouraging results in a canine study of advanced and metastatic cancer, and encouraging results in a phase 1/2 study of advanced and metastatic cancer in 42 patients. Finally, we have hypothesized that the pathway of fibrosis involving transforming growth factor beta (TGF-beta) and connective tissue growth factor is inhibitable by copper-lowering therapy with TM. This pathway is overactive and dysregulated in many diseases of fibrosis. In animal studies, TM has completely inhibited the pulmonary fibrosis induced by bleomycin, the hepatitis induced by concanavalin A, and the cirrhosis induced by carbon tetrachloride. We find that TM inhibits transforming growth factor beta and inflammatory cytokines tumor necrosis factor alpha and interleukin-1-beta. © 2003 Wiley-Liss, Inc.",Antiangiogenesis;Anticopper drugs;Cytokines;Transforming growth factor beta;Tumor necrosis factor alpha;Wilson's disease;anemia/si [Side Effect];angiogenesis;antiinflammatory activity;antineoplastic activity;cancer growth;cancer inhibition;conference paper;copper deficiency/si [Side Effect];copper metabolism;drug efficacy;fibrosis/dt [Drug Therapy];fibrosis/et [Etiology];human;leukopenia/si [Side Effect];liver cirrhosis/dt [Drug Therapy];liver cirrhosis/et [Etiology];liver dysfunction/si [Side Effect];lung fibrosis/dt [Drug Therapy];lung fibrosis/et [Etiology];nonhuman;priority journal;sickle cell anemia/dt [Drug Therapy];side effect/si [Side Effect];tumor vascularization;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];connective tissue growth factor/ec [Endogenous Compound];copper;immunoglobulin enhancer binding protein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];transforming growth factor beta/ec [Endogenous Compound];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];tumor necrosis factor alpha/ec [Endogenous Compound];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Brewer, G. J.",2003,,http://dx.doi.org/10.1002/jtra.10045,0,0,
2258,A Case of Penicillamine-induced Dermopathy,"Introduction: We describe an interesting patient with penicillamine-induced dermopathy. Clinical Picture: A 49-year-old woman presented with a 1-year history of recurrent haemorrhagic blisters, milia and purpura over both her elbows, while on long-term penicillamine therapy (1.5 g daily) for Wilson's disease. Histologically, dermal elastin fibres were markedly reduced in the affected areas, consistent with penicillamine-induced elastolysis. Treatment and Outcome: The patient's lesions improved significantly after reduction of her penicillamine dose to 500 mg daily. Conclusions: The cutaneous side effects of long-term penicillamine therapy are important to recognise as they may be associated with significant morbidity and may be markers of more ominous underlying systemic elastic fibre damage.",Elastolysis;Haemorrhagic blisters;Purpura;Wilson's disease;adult;article;bullous skin disease/si [Side Effect];case report;differential diagnosis;dose response;drug induced disease/si [Side Effect];elastolysis/si [Side Effect];female;follow up;hospitalization;human;human tissue;iatrogenic disease;immunohistochemistry;long term care;needle biopsy;pathophysiology;purpura/si [Side Effect];risk assessment;skin biopsy;skin disease/si [Side Effect];sweat gland disease/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Tang, M. B. Y.;Chin, T. M.;Yap, C. K.;Ng, S. K.",2003,September,,0,0,
2259,Opinion and evidence in neurology and psychiatry,"The management of neurological and psychiatric disorders is a vast and evolving area for researchers, primary care physicians and specialists. To help you keep up to date with the latest advances worldwide on all aspects of drug therapy for neurological and psychiatric disorders, this section of the journal brings you information selected from the drug therapy reporting service Inpharma Weekly. The following reports are selected from the latest issues, summarising the most important research and development news, clinical studies, treatment guidelines, pharmacological, pharmacoeconomic and adverse drug reactions/interactions news, and expert opinion pieces published across a broad range of literature sources.",aphasia/dt [Drug Therapy];attention deficit disorder/dt [Drug Therapy];autism;bipolar disorder/dt [Drug Therapy];bone marrow suppression/si [Side Effect];cerebrovascular accident/dt [Drug Therapy];clinical trial;depression/dt [Drug Therapy];disease association;drug cost;drug dose reduction;drug efficacy;drug exposure;drug formulation;drug receptor binding;drug release;drug safety;drug targeting;drug tolerability;drug withdrawal;epilepsy/dm [Disease Management];epilepsy/dt [Drug Therapy];extrapyramidal symptom/si [Side Effect];generalized anxiety disorder/dt [Drug Therapy];human;Huntington chorea;long term care;maternal hypertension;measles;mental disease/dt [Drug Therapy];meta analysis;mumps;neurologic disease/dt [Drug Therapy];neuroprotection;nonhuman;paresthesia/si [Side Effect];prenatal exposure;prescription;primary medical care;priority journal;quality adjusted life year;review;risk factor;rubella;schizophrenia/si [Side Effect];side effect/si [Side Effect];treatment outcome;vertigo/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];antidepressant agent/dt [Drug Therapy];anxiolytic agent/dt [Drug Therapy];benzodiazepine derivative/dt [Drug Therapy];benzodiazepine derivative/pd [Pharmacology];benzodiazepine receptor stimulating agent/dt [Drug Therapy];benzodiazepine receptor stimulating agent/pd [Pharmacology];carbamazepine/ae [Adverse Drug Reaction];carbamazepine/ct [Clinical Trial];carbamazepine/cm [Drug Comparison];carbamazepine/do [Drug Dose];carbamazepine/dt [Drug Therapy];clozapine/ae [Adverse Drug Reaction];clozapine/ct [Clinical Trial];clozapine/dt [Drug Therapy];diuretic agent/ae [Adverse Drug Reaction];donepezil/ae [Adverse Drug Reaction];donepezil/ct [Clinical Trial];donepezil/do [Drug Dose];donepezil/dt [Drug Therapy];huntingtin;lamotrigine/ct [Clinical Trial];lamotrigine/cb [Drug Combination];lamotrigine/do [Drug Dose];lamotrigine/dt [Drug Therapy];lithium/ct [Clinical Trial];lithium/cb [Drug Combination];lithium/do [Drug Dose];lithium/dt [Drug Therapy];lorazepam/ae [Adverse Drug Reaction];lorazepam/ct [Clinical Trial];lorazepam/dt [Drug Therapy];measles mumps rubella vaccine;metabotropic receptor agonist/dt [Drug Therapy];metabotropic receptor agonist/pd [Pharmacology];methylphenidate/ae [Adverse Drug Reaction];methylphenidate/ct [Clinical Trial];methylphenidate/do [Drug Dose];methylphenidate/dt [Drug Therapy];methylphenidate/pr [Pharmaceutics];methylphenidate/pk [Pharmacokinetics];n methyl dextro aspartic acid receptor blocking agent/dt [Drug Therapy];n methyl dextro aspartic acid receptor blocking agent/pd [Pharmacology];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/ct [Clinical Trial];neuroleptic agent/dt [Drug Therapy];olanzapine/ct [Clinical Trial];olanzapine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pregabalin/ae [Adverse Drug Reaction];pregabalin/ct [Clinical Trial];pregabalin/dt [Drug Therapy];protein S/dv [Drug Development];protein S/do [Drug Dose];protein S/dt [Drug Therapy];protein S/pd [Pharmacology];serotonin uptake inhibitor/ae [Adverse Drug Reaction];serotonin uptake inhibitor/ct [Clinical Trial];serotonin uptake inhibitor/cm [Drug Comparison];serotonin uptake inhibitor/dt [Drug Therapy];tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/do [Drug Dose];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];topiramate/ae [Adverse Drug Reaction];topiramate/ct [Clinical Trial];topiramate/cm [Drug Comparison];topiramate/do [Drug Dose];topiramate/dt [Drug Therapy];topiramate/pe [Pharmacoeconomics];tricyclic antidepressant agent/ae [Adverse Drug Reaction];tricyclic antidepressant agent/ct [Clinical Trial];tricyclic antidepressant agent/cm [Drug Comparison];tricyclic antidepressant agent/dt [Drug Therapy];unindexed drug;valproic acid/ae [Adverse Drug Reaction];valproic acid/ct [Clinical Trial];valproic acid/do [Drug Dose];valproic acid/dt [Drug Therapy];zinc/dt [Drug Therapy];zolmitriptan/ct [Clinical Trial];zolmitriptan/do [Drug Dose];zolmitriptan/dt [Drug Therapy];zolmitriptan/po [Oral Drug Administration],Anonymous,2003,,,0,0,
2260,Trace element risk assessment: Essentiality vs. toxicity,"Risk assessment of essential trace elements examines high intakes resulting in toxicity and low intakes resulting in nutritional deficiencies. This paper analyzes the risk assessments carried out by several U.S. governmental and private organizations for eight essential trace elements: chromium, copper, iodine, iron, manganese, molybdenum, selenium, and zinc. The compatibility of the toxicity values with the nutritionally essential values is examined, in light of recently derived values, termed Dietary Reference Intakes, set by the U.S. Food and Nutrition Board of the Institute of Medicine. The results show that although there are differences in the values set by the different organizations, increased coordination has resulted in values that are more compatible than revealed in past evaluations. © 2003 Elsevier Inc. All rights reserved.",Adequate intake;Dietary reference intake;Essential elements;Estimated average requirement;Recommended daily allowance;Reference daily intake;Reference dose;Risk assessment;Tolerable upper intake level;Trace elements;anemia;cardiovascular disease;congenital hypothyroidism;congenital malformation;death;diarrhea;dietary intake;exposure;food and drug administration;gastrointestinal disease;glucose metabolism;goiter;health hazard;heavy metal poisoning;hemochromatosis;human;immune system;intoxication;kidney disease;liver disease;lung cancer;mental deficiency;mental disease;neurologic disease;nonhuman;nutritional deficiency;nutritional requirement;nutritional value;priority journal;reference value;reproduction;review;safety;thyroid disease;thyroid papillary carcinoma;toxicity testing;vomiting;Wilson disease;world health organization;chromium;copper;iodine;iron;manganese;molybdenum;selenium;trace element;zinc,"Goldhaber, S. B.",2003,October,http://dx.doi.org/10.1016/S0273-2300%2802%2900020-X,0,0,
2261,Role of genetic testing in liver transplantation for Wilson's disease,,allele;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/su [Surgery];clinical feature;conference paper;diagnostic test;disease course;exon;gene frequency;gene mutation;genetic analysis;genetic screening;heterozygosity;homozygosity;human;intron;laboratory test;liver transplantation;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];protein/ec [Endogenous Compound];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Schmidt, H. H. J.",2003,September,http://dx.doi.org/10.1016/S0041-1345%2803%2900671-7,0,0,
2262,Excess dietary histidine decreases the liver copper level and serum alanine aminotransferase activity in Long-Evans Cinnamon rats,"Long-Evans Cinnamon (LEC) rats spontaneously develop fulminant hepatitis, associated with excess Cu accumulation in the liver: thus, they are considered an animal model of Wilson's disease. In the present study, we investigated the ability of excess dietary histidine to reduce the excess accumulation of liver Cu in LEC rats by comparing them with Fischer rats. The results clearly showed that the excess-histidine diet markedly stimulated the Cu excretion in urine, and significantly decreased the liver Cu content in LEG rats by 47.5%. The serum Cu content in LEC rats was not influenced by excess dietary histidine. We also compared the effects of excess dietary histidine on some liver antioxidant enzyme activities, liver and serum lipid levels and serum alanine aminotransferase activity of LEC and Fischer rats. Dietary histidine decreased the activities of total and Cu,Zn-superoxide dismutase in the liver of both strains. In LEC rats, the liver cholesterol content decreased, and serum cholesterol and phospholipids levels increased on feeding the excess-histidine diet. When fed on the basal diet, the serum alanine aminotransferase activity was higher in LEC rats than in Fischer rats, but a significant decrease in serum alanine aminotransferase activity of LEC rats was observed on feeding the excess-histidine diet. These results suggest that excess dietary histidine is effective in removing Cu ions from the liver of LEC rats. Thus, it may be of benefit in the prevention or treatment of liver injury in LEC rats and in patients with Wilson's disease.",Alanine aminotransferase;Copper;Histidine;Long-Evans Cinnamon rats;alanine aminotransferase blood level;animal experiment;animal model;animal tissue;article;cholesterol blood level;cholesterol liver level;controlled study;copper blood level;copper metabolism;diet;enzyme activity;feeding;lipid blood level;lipid liver level;liver injury/pc [Prevention];liver injury/th [Therapy];liver level;male;nonhuman;phospholipid blood level;rat;rat strain;strain difference;triacylglycerol blood level;urinary excretion;Wilson disease/pc [Prevention];Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];catalase/ec [Endogenous Compound];cholesterol/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper ion/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];glutathione peroxidase/ec [Endogenous Compound];lipid/ec [Endogenous Compound];phospholipid/ec [Endogenous Compound];triacylglycerol/ec [Endogenous Compound],"Xu, H.;Sakakibara, S.;Morifuji, M.;Salamatulla, Q.;Aoyama, Y.",2003,01 Sep,http://dx.doi.org/10.1079/BJN2003939,0,0,
2263,Wilson's disease and pregnancy. [Spanish],"Wilson's disease is an autosomal recessive disorder. It is characterized by the accumulation of large quantities of copper in the organism, especially in the liver and the brain. The disease appears as a consequence of a deficit in biliary excretion of copper. The defective gene responsible for the disease is located on the 13th chromosome. It usually manifests in childhood, although never before 5 years of age, or during adolescence. More rarely in young adults it appears in the form of hepatic, neurological or psychiatric disease. A retrospective analysis was made of all cases of Wilson's disease during pregnancy registered in our hospital from 1993 to 2003.",Apgar score;article;autosomal recessive disorder/cn [Congenital Disorder];autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/et [Etiology];biliary excretion;birth weight;chromosome 13;clinical article;controlled study;female;human;liver failure;male;newborn;pregnancy;retrospective study;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper;penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration],"Barber, M. A.;Eguiluz, I.;Plasencia, W.;Ramirez, O.",2003,December,,0,0,
2264,Late-onset Wilson's disease. [Spanish],"A 58-year old male with a past history ofpsychiatric disorders was studied for a persistent serum transaminase increase. Low serum ceruloplasmin level (lower than 3 mg/dL), increased urinary copper excretion, and increased liver tissue copper concentration (1050 mcg/g dry weight) confirmed the diagnosis of Wilson's disease. Slit lamp examination did not show Kayser-Fleischer rings. D-penicilamin therapy was followed by serum transaminase normalization. Similar late-onset cases of Wilson's disease are exceptional, but confirm the clinical heterogeneity of the disease.",Copper;Late-onset;Wilson's disease;adult;aminotransferase blood level;article;case report;ceruloplasmin blood level;human;male;mental disease;onset age;slit lamp;urinary copper excretion;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Campos Franco, J.;Dominguez Santalla Ma, J.;Tome Martinez De Rituerto, S.;Otero Anton, E.;Gonzalez Quintela, A.",2003,01 Aug,,0,0,
2265,Wilson's disease: From misleading onset to dramatic progression without treatment. [French],,clinical examination;clinical feature;copper metabolism;disease course;human;liver metabolism;pathophysiology;review;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper;metalite;penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];trientine/do [Drug Dose];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Reinert, P.",2003,March/April,,0,0,
2266,Boon and bane of metal ions in medicine,"In biological systems metal ions promote responses that range from deficiency to toxicity. Some, such as iron and zinc, have a known optimal intake range for normal, healthy individuals. Metal ions contained within well-designed molecules already constitute a great boon for the medicinal pharmacopoeia. However, whether essential or not, the threshold for toxicity can be very low. One of the challenges of designing metal-based drugs is to balance the potential toxicity of an active formulation with the substantial positive impact of these increasingly common therapeutic and diagnostic aids.",arthritis/dt [Drug Therapy];bioavailability;biology;bipolar disorder/dt [Drug Therapy];bone pain/dt [Drug Therapy];cancer/dt [Drug Therapy];catalysis;chemistry;clinical trial;dose response;drug design;electronics;gastrointestinal symptom/dt [Drug Therapy];human;imaging;intoxication/et [Etiology];medical literature;medicine;nonhuman;nutritional deficiency/et [Etiology];ovary cancer/dt [Drug Therapy];oxidation reduction state;physical chemistry;priority journal;reference value;review;therapy;trypanosomiasis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];auranofin/dt [Drug Therapy];barium sulfate;bismuth derivative/dt [Drug Therapy];bismuth derivative/pd [Pharmacology];bismuth salicylate/dt [Drug Therapy];carboplatin/dt [Drug Therapy];catalase;chelating agent/dt [Drug Therapy];chromium/dt [Drug Therapy];chromium picolinate/pd [Pharmacology];cisplatin/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];drug;gadobenic acid;gallium citrate ga 67;iron/dt [Drug Therapy];iron/to [Drug Toxicity];lexidronam samarium sm 153/dt [Drug Therapy];lithium carbonate/dt [Drug Therapy];macrocyclic compound/ct [Clinical Trial];manganese derivative/ct [Clinical Trial];manganese superoxide dismutase;metal ion/dt [Drug Therapy];metal ion/to [Drug Toxicity];methoxy isobutyl isonitrile technetium tc 99m;multivitamin;penicillamine/dt [Drug Therapy];pentetate indium in 111;platinum/to [Drug Toxicity];selenium/to [Drug Toxicity];trientine/dt [Drug Therapy];unindexed drug;zinc,"Thompson, K. H.;Orvig, C.",2003,09 May,http://dx.doi.org/10.1126/science.1083004,0,0,
2267,Elevation of serum copper levels in Alzheimer's disease [3] (multiple letters),,aging;Alzheimer disease/et [Etiology];controlled study;copper blood level;diet;glia cell;human;letter;lifestyle;neurotoxicity;olfactory system;priority journal;Wilson disease;carnosine/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Brenner, S.;Squitti, R.;Lupoi, D.;Pasqualetti, P.;Dal Forno, G.;Vernieri, F.;Chiovenda, P.;Rossi, L.;Cortesi, M.;Cassetta, E.;Rossini, P. M.",2003,13 May,,0,0,
2268,Copper in medicine,"Copper has been found to be causative in several diseases. New findings with the greatest potential for impact in medicine include the use of copper-lowering therapy for antiangiogenesis, antifibrotic and anti-inflammatory purposes. The indication of the role of copper in formation of amyloid plaques in Alzheimer's disease, and successful treatment of an Alzheimer's rodent model by copper chelation are also potentially important. There have also been recent developments in the genetic and non-genetic abnormalities of copper, including the finding of new copper-related genes that potentially could cause disease if mutated.",aceruloplasminemia;Alzheimer disease;angiogenesis;autosomal recessive disorder;clinical trial;copper deficiency;copper metabolism;fibrosis;gene mutation;human;inflammation;intoxication;Menkes syndrome;nonhuman;retinopathy;review;senile plaque;Wilson disease;copper/to [Drug Toxicity];tetrathiomolybdic acid/pd [Pharmacology],"Brewer, G. J.",2003,April,http://dx.doi.org/10.1016/S1367-5931%2803%2900018-8,0,0,
2269,Wilson's disease: The importance of measuring serum caeruloplasmin non-immunologically,"Wilson's disease should be considered as a possible diagnosis in any child, adolescent or young adult with liver damage without other explanation, especially when haemolysis is present. However, it may also present in adolescents or young adults with neurological signs confined to the motor system. The first diagnostic screening test is the estimation of the serum caeruloplasmin and total serum copper concentrations, with calculation of the serum non-caeruloplasmin-bound ('free') copper. Serum caeruloplasmin, which contains copper, is best determined by measurement of its oxidase activity, as the immunonephelometric method measures both caeruloplasmin and the biologically inactive apo-form. Diagnosis may be confirmed by an elevated urinary copper excretion. All close relatives of an identified patient must be screened and, where doubt persists, investigation of the Wilson's gene at chromosome 13q14.3 can be employed. Lifelong follow-up studies are best conducted in a specialist centre. Compliance with chelating therapy (penicillamine or trientine) or administration of the metal antagonist tetrathiomolybdate or zinc is monitored by determination of the serum 'free' copper, which should be maintained at or near 1.6 mumol/L (10 mug/100 mL). Side-effects of therapy are detected by the estimation of urinary total protein, full blood count and erythrocyte sedimentation rate, clotting factors and liver function tests.",anemia/si [Side Effect];blood toxicity/si [Side Effect];bone marrow depression;calculation;ceruloplasmin blood level;chromosome 13q;clinical feature;copper blood level;diagnostic test;drug efficacy;enzyme activity;erythrocyte sedimentation rate;follow up;gene identification;genetic analysis;hemolysis;human;iron deficiency anemia/si [Side Effect];liver function test;liver injury;motor system;nephelometry;nephritis/si [Side Effect];nephrotoxicity/si [Side Effect];neurologic disease;nonhuman;patient compliance;priority journal;protein urine level;review;screening test;side effect/si [Side Effect];sideroblastic anemia/si [Side Effect];systemic lupus erythematosus/si [Side Effect];thrombocytopenia/si [Side Effect];urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha tocopherol/cb [Drug Combination];alpha tocopherol/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];chelating agent/im [Intramuscular Drug Administration];chelating agent/pd [Pharmacology];copper/ec [Endogenous Compound];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];oxidoreductase/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Walshe, J. M.",2003,March,http://dx.doi.org/10.1258/000456303763046021,0,0,
2270,"Wilson's disease: Physiopathological, clinical and therapeutic considerations. [Spanish]",,brain blood flow;clinical observation;human;nuclear magnetic resonance imaging;pathophysiology;prognosis;review;treatment planning;Wilson disease/et [Etiology];antioxidant;ceruloplasmin;penicillamine,"Perez-Aguilar, F.",2003,January,http://dx.doi.org/10.1157/13042214,0,0,
2271,Neglected zinc,,bioavailability;cereal;chronic liver disease/et [Etiology];diabetes mellitus/et [Etiology];diet supplementation;dietary intake;gene activation;hormonal regulation;malabsorption/et [Etiology];note;protein synthesis;retina macula degeneration/et [Etiology];sickle cell anemia/et [Etiology];Wilson disease/et [Etiology];zinc deficiency;zinc,Anonymous,2003,22 Mar,,0,0,
2272,"Effect and possible role of Zn treatment in LEC rats, an animal model of Wilson's disease","The effect of oral zinc (Zn) treatment was studied in the liver, kidneys and intestine of Long-Evans Cinnamon (LEC) rats in relation to metals interaction and concentration of metallothionein (MT) and glutathione (GSH). We also investigated the change in the activity of antioxidant enzymes and determined the biochemical profile in the blood and metal levels in urine. We showed that the Zn-treated group had higher levels of MT in the hepatic and intestinal cells compared to both untreated and basal groups. Tissue Zn concentrations were significantly higher in the Zn-treated group compared to those untreated and basal, whereas Cu and Fe concentrations decreased. The antioxidant enzyme activities in the Zn-treated group did not change significantly with respect to those in the basal group, except for hepatic glutathione peroxidase activity. Moreover, the biochemical data in the blood of Zn-treated group clearly ascertain no liver damage. These observations suggest an important role for Zn in relation not only to its ability to compete with other metals at the level of absorption in the gastrointestinal tract producing a decrease in the hepatic and renal Cu and Fe deposits, but also to MT induction as free radical scavenger. © 2002 Elsevier Science B.V. All rights reserved.",Antioxidant enzyme;Glutathione;LEC rat;Metallothionein;Oxidative stress;Trace element;absorption;animal experiment;animal model;animal tissue;article;blood analysis;cell level;controlled study;copper metabolism;correlation analysis;disease model;drug effect;enzyme activity;enzyme assay;experimental rat;gastrointestinal tract;glutathione metabolism;intestine;intestine cell;iron metabolism;kidney;liver;liver cell;liver injury;male;nonhuman;priority journal;rat;tissue level;urine level;Wilson disease/dt [Drug Therapy];antioxidant/ec [Endogenous Compound];copper/ec [Endogenous Compound];enzyme/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];glutathione peroxidase/ec [Endogenous Compound];iron/ec [Endogenous Compound];metal;metallothionein/ec [Endogenous Compound];scavenger/ec [Endogenous Compound];zinc/cr [Drug Concentration];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc/pd [Pharmacology],"Santon, A.;Irato, P.;Medici, V.;D'Inca, R.;Albergoni, V.;Sturniolo, G. C.",2003,20 Jan,http://dx.doi.org/10.1016/S0925-4439%2802%2900218-1,0,0,
2273,From gene to disease; Wilson's disease: Copper accumulation due to ATP7B mutations [4]. [Dutch],,clinical trial;gene mutation;genetic analysis;human;letter;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper;zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration],"Hoogenraad, T. U.",2003,12 Jul,,0,0,
2274,"Copper toxicity, oxidative stress, and antioxidant nutrients","Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Although normally bound to proteins, Cu may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of Cu's capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic Cu-overload and/or exposure to excess Cu caused by accidents, occupational hazards, and environmental contamination. Additionally, Cu-induced oxidative damage has been implicated in disorders associated with abnormal Cu metabolism and neurodegenerative changes. Interestingly, a deficiency in dietary Cu also increases cellular susceptibility to oxidative damage. A number of nutrients have been shown to interact with Cu and alter its cellular effects. Vitamin E is generally protective against Cu-induced oxidative damage. While most in vitro or cell culture studies show that ascorbic acid aggravates Cu-induced oxidative damage, results obtained from available animal studies suggest that the compound is protective. High intakes of ascorbic acid and zinc may provide protection against Cu toxicity by preventing excess Cu uptake. Zinc also removes Cu from its binding site, where it may cause free radical formation. Beta-carotene, alpha-lipoic acid and polyphenols have also been shown to attenuate Cu-induced oxidative damage. Further studies are needed to better understand the cellular effects of this essential, but potentially toxic, trace mineral and its functional interaction with other nutrients. © 2003 Elsevier Science Ireland Ltd. All rights reserved.",Ascorbic acid;Copper;Oxidative stress;Vitamin E;acute kidney tubule necrosis/et [Etiology];Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];Alzheimer disease/pc [Prevention];binding site;cell culture;cholesterol metabolism;copper deficiency/dt [Drug Therapy];copper deficiency/et [Etiology];copper metabolism;diet supplementation;DNA damage;enzyme activity;gastrointestinal toxicity/et [Etiology];human;liver cirrhosis/et [Etiology];liver injury/dt [Drug Therapy];liver injury/et [Etiology];liver injury/pc [Prevention];nerve degeneration/et [Etiology];neurotoxicity/et [Etiology];nonhuman;occupational hazard;oxidation;pathogenesis;pollutant;priority journal;review;vitamin intake;vitamin supplementation;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha tocopherol/dt [Drug Therapy];alpha tocopherol/po [Oral Drug Administration];alpha tocopherol/pd [Pharmacology];amyloid protein/ec [Endogenous Compound];antioxidant/dt [Drug Therapy];antioxidant/ip [Intraperitoneal Drug Administration];antioxidant/iv [Intravenous Drug Administration];antioxidant/po [Oral Drug Administration];antioxidant/pd [Pharmacology];ascorbic acid/dt [Drug Therapy];ascorbic acid/ip [Intraperitoneal Drug Administration];ascorbic acid/iv [Intravenous Drug Administration];ascorbic acid/po [Oral Drug Administration];ascorbic acid/pd [Pharmacology];beta carotene/dt [Drug Therapy];beta carotene/pd [Pharmacology];catalase/ec [Endogenous Compound];cholesterol/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/to [Drug Toxicity];copper/pd [Pharmacology];hydroxyl radical/ec [Endogenous Compound];iron/to [Drug Toxicity];manganese superoxide dismutase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];polyphenol derivative/pd [Pharmacology];proline/po [Oral Drug Administration];proline/pd [Pharmacology];selenium/dt [Drug Therapy];selenium/po [Oral Drug Administration];selenium/pd [Pharmacology];thioctic acid/pd [Pharmacology];zinc/to [Drug Toxicity];zinc/pd [Pharmacology],"Gaetke, L. M.;Chow, C. K.",2003,15 Jul,http://dx.doi.org/10.1016/S0300-483X%2803%2900159-8,0,0,
2275,Animal models of copper-associated liver disease,"Recent advances in molecular biology have made possible the identification of genetic defects responsible for Wilson's disease, Indian childhood cirrhosis and copper toxicosis in Long Evans Cinnamon rats, toxic milk mice, and Bedlington terriers. The Wilson's disease gene is localized on human chromosome 13 and codes for ATP7B, a copper transporting P-type ATPase. A genetic defect similar to that of Wilson's disease occurs in Long Evans Cinnamon rats and toxic milk mice. Familial copper storage disorders in Bedlington and West Highland white terriers are associated with early subclinical disease, and copper accumulation with subsequent liver injury culminating in cirrhosis. The canine copper toxicosis locus in Bedlington terriers has been mapped to canine chromosome region CFA 10q26. Recently, a mutated MURR1 gene was discovered in Bedlington terriers affected with the disease. Idiopathic childhood cirrhosis is biochemically similar to copper toxicosis in Bedlington terriers, but clinically much more severe. Both conditions are characterized by the absence of neurologic damage and Kayser-Fleisher rings, and normal ceruloplasmin levels. A recent study added North Ronaldsay sheep to the list of promising animal models to study Indian childhood cirrhosis. Morphologic similarities between the two conditions include periportal to panlobular copper retention and liver changes varying from active hepatitis to panlobular pericellular fibrosis, and cirrhosis. Certain copper-associated disorders, such as chronic active hepatitis in Doberman pinschers and Skye terrier hepatitis are characterized by copper retention secondary to the underlying disease, thus resembling primary biliary cirrhosis in humans. Copper-associated liver disease has increasingly being recognized in Dalmatians. Copper-associated liver diseases in Dalmatians and Long Evans Cinnamom rats share many morphologic features. Fulminant hepatic failure in Dalmatians is characterized by high serum activities of alanine aminotransferase and aspartate aminotransferase, and severe necrosis of centrilobular areas (periacinar, zone 3) hepatocytes. Macrophages and surviving hepatocytes contain copper-positive material. Liver disease associated with periacinar copper accumulation has also been described in Siamese cats. Many questions regarding copper metabolism in mammals, genetic background, pathogenesis and treatment of copper-associated liver diseases remain to be answered. This review describes the similarities between the clinico-pathological features of spontaneous copper-associated diseases in humans and domestic animals. © 2003 Fuentealba and Aburto; licensee Bio Med Centreal Ltd.",acinar cell;alanine aminotransferase blood level;animal model;anorexia/si [Side Effect];aspartate aminotransferase blood level;bioaccumulation;biochemistry;breeding line;cat;cell survival;chromosome 10q;chromosome 13;chronic active hepatitis/et [Etiology];clinical feature;copper metabolism;disease association;disease severity;dog;domestic animal;drug efficacy;drug eruption/si [Side Effect];drug excretion;drug tissue level;enzyme activity;familial disease/et [Etiology];fever/si [Side Effect];gene location;gene locus;gene mapping;gene mutation;genetic code;genetic disorder;hepatitis/et [Etiology];human;idiopathic disease/et [Etiology];Indian childhood cirrhosis/et [Etiology];leukopenia/si [Side Effect];liver cirrhosis;liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver failure;liver fibrosis;liver injury/et [Etiology];liver toxicity/dt [Drug Therapy];liver toxicity/et [Etiology];macrophage;mammal;molecular biology;morphology;nervous system injury;nonhuman;pathogenesis;portal vein;primary biliary cirrhosis;proteinuria/si [Side Effect];pyridoxine deficiency/si [Side Effect];rat strain;review;sheep;storage disease/et [Etiology];thrombocytopenia/si [Side Effect];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity];penicillamine/pd [Pharmacology];pyridoxine/ec [Endogenous Compound];tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdate ammonium/pd [Pharmacology];tetrathiomolybdic acid/cr [Drug Concentration];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Fuentealba, I. C.;Aburto, E. M.",2003,03 Apr,http://dx.doi.org/10.1186/1476-5926-2-5,0,0,
2276,Pathogenesis and treatment of Wilson's disease. [Hungarian],"Authors review the pathogenesis, symptoms and diagnosis of Wilson's disease. Wilson's disease or hepatolenticular degeneration is an autosomal recessive disorder. It is caused by defective hepatic excretion of copper. The disease is fatal without treatment. The prevention of severe permanent damage depends upon early recognition and diagnosis followed by appropriate lifelong anticopper treatment. The purpose of the therapy of Wilson's disease is to eliminate the copper by chelators (D-penicillamine, triethylene tetramine, ammonium tetrathiomolibdate) and to inhibit the absorption and accumulation of copper by zinc salts (zinc sulphate, zinc acetate, zinc gluconate).",autosomal recessive disorder/cn [Congenital Disorder];autosomal recessive disorder/di [Diagnosis];copper metabolism;diagnostic value;disease severity;drug absorption;drug accumulation;drug fatality;early diagnosis;human;liver disease;pathogenesis;review;symptomatology;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];gluconate zinc/pd [Pharmacology];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/pd [Pharmacology];zinc derivative/pd [Pharmacology];zinc sulfate/pd [Pharmacology],"Nagy, J.;Vincze, Z.;Folhoffer, A.;Horvath, A.;Csak, T.;Zelko, R.",2003,,,0,0,
2277,Wilson's disease. [Croatian],"Wilson's disease is an autosomal recessive disorder of copper metabolism. The Wilson disease protein is a copper-transporting P-type ATPase, ATP7B, the malfunction of which results in the toxic accumulation of copper in the liver and brain, causing the hepatic and/or neurological symptoms accompanying this disease. Patients present, generally between the ages of 10 and 40 years, with liver disease, neurological disease of a movement disorder type, or behavioral abnormalities, and often with a combination of these. Because Wilson's disease is effectively treated, it is extremely important for physicians to learn to recognize and diagnose the disease. The laboratory diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper content, and elevated hepatic copper concentration. Molecular genetic analysis is complex as more than 200 unique mutations have been identified and most individuals are compound heterozygotes. The treatment of Wilson's disease must be life long. Copper chelation with penicillamine is an effective therapy in most patients. Another chelating agent which has been used successfully as the initial therapy is trientine. The search for new anticopper drugs for Wilson's disease is culminating in two excellent new drugs: zinc for maintenance therapy and ammonium tetrathiomolybdate (which is to date still an experimental drug) for initial therapy. Liver transplantation is indicated for the fulminant form and in those patients with severe disease not responding to optimal medical management. This paper reviews the pathogenesis, pathology, clinical presentation and diagnosis of the Wilson's disease as well as the most recent views on the molecular genetics and the treatment of this disease.",Copper metabolism;Diagnosis;Treatment;Wilson's disease;autosomal recessive disorder/cn [Congenital Disorder];autosomal recessive disorder/di [Diagnosis];behavior disorder/di [Diagnosis];brain level;ceruloplasmin blood level;chelation;clinical feature;concentration response;copper blood level;copper liver level;copper urine level;diagnostic accuracy;disease severity;enzyme kinetics;gene identification;gene mutation;heterozygote;human;liver disease/di [Diagnosis];liver level;liver transplantation;maintenance therapy;molecular genetics;motor dysfunction/di [Diagnosis];neurological complication;pathogenesis;pathophysiology;review;symptomatology;treatment indication;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Kovacevic, I.;Zekan, M.",2003,,,0,0,
2278,Non-gastrointestinal bleeding as leading sign of impaired haemostasis on Wilson's disease,Wilson disease is one of the chronic liver diseases in which hemostasis can be impaired by various mechanisms. Gastrointestinal hemorrhages caused by ruptured esophageal varices or as complication of peptic ulcer can be relatively frequent in Wilson disease. We are presenting two pediatric patients with non-gastrointestinal bleeding as the leading sign of Wilson disease.,Bleeding;Hemostasis;Wilson disease;adolescent;article;ascites/dt [Drug Therapy];case report;chronic liver disease;esophagus varices bleeding;female;gastrointestinal hemorrhage;hematuria/si [Side Effect];human;male;peptic ulcer;rash/si [Side Effect];school child;urticaria/si [Side Effect];Wilson disease/dt [Drug Therapy];albumin/dt [Drug Therapy];albumin/iv [Intravenous Drug Administration];furosemide/dt [Drug Therapy];furosemide/iv [Intravenous Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];trientine/cj [Subconjunctival Drug Administration];zinc sulfate/dt [Drug Therapy],"Duric, Z.;Perisic, V. N.;Kostic, G.;Golubovic, E.",2003,July/December,,0,0,
2279,Wilson's Disease Associated with Olfactory Paranoid Syndrome and Idiopathic Thrombocytopenic Purpura. [Japanese],"In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.",Idiopathic thrombocytopenic purpura;mri;Olfactory paranoid syndrome;Wilson disease;adolescent;article;bioaccumulation;blood analysis;case report;ceruloplasmin blood level;chronic hepatitis;copper blood level;diffusion;disease activity;disease association;disease control;disease course;disease exacerbation;dysarthria;extrapyramidal symptom;female;finger;gait disorder;general condition improvement;histology;human;hypersalivation;idiopathic thrombocytopenic purpura/co [Complication];idiopathic thrombocytopenic purpura/di [Diagnosis];image analysis;limb;liver biopsy;mental disease/dt [Drug Therapy];muscle rigidity;neurologic examination;nuclear magnetic resonance imaging;olfactory system;paranoia/dt [Drug Therapy];paranoid psychosis/co [Complication];patient referral;pons;putamen;symptom;tegmentum;thalamus;treatment outcome;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];bromperidol;ceruloplasmin/ec [Endogenous Compound];chlorpromazine;copper/ec [Endogenous Compound];fluphenazine;haloperidol;olanzapine;penicillamine/dt [Drug Therapy];periciazine;perphenazine;risperidone;sulpiride,"Sagawa, M.;Takao, M.;Nogawa, S.;Mizuno, M.;Murata, M.;Amano, T.;Koto, A.",2003,October,,0,0,
2280,"Rare, but important chronic liver diseases. [German]","The presence of steatosis and inflammatory infiltrate in liver biopsies is essential for the diagnosis of non-alcoholic steatohepatitis (NASH). These findings are similar to those with alcoholic liver disease. However, in the NASH-situation alcohol doesn't play an important role. Risk factors for the development of NASH are obesity and diabetes. Most of the patients are clinically asymptomatic. This means, that a diagnosis of NASH is a diagnosis of exclusion: Viral induced, autoimmune, metabolic and toxic liver disease have to be excluded. The disease has a benign clinical course. The risk of cirrhosis is low. So far, there is no established treatment. Preliminary reports suggest a positive effect of weight-loss and ursodeoxycholic acid. Wilson's disease, a copper storage disorder, in which biliary copper excretion is reduced, is inherited as an autosomal recessive trait. Most patients with Wilson disease become symptomatic between the ages of 6 and 15. In about 90% of patients serum ceruloplasmin levels and serum copper concentrations are reduced. Copper excreation is increased. Histologic examination of liver biopsy specimens reveals fatty infiltration, Mallory bodies and ballooned glycogen nuclei, abnormalities which are also found in alcoholic liver disease. The definitive diagnostic parameter is the quantitative determination of liver copper content (> 250 micrograms/g dryweight). Untreated Wilson disease is always fatal. Lifelong treatment with anti-copper drugs are essential, D-penicillamine being the firstline therapy. Hereditary hemochromatosis (HH) is an iron overload disease inherited as an autosomal recessive trait. The frequency of the disease is high. The first symptoms usually can be found at the age of 20-50 years. Arthralgia develops in up to 50% of the patients. Many organs are involved, most often the liver. The organ is usually enlarged, transaminases are always moderately elevated. Laboratory findings disclose a marked elevation in serum ferritin and transferrin saturation. More than 80% of HH-patients are homozygous for the C282Y-mutation in the HFE-gene. The firstline treatment of HH is phlebotomy. Treatment is lifelong. When serum ferritin drops below 50 micrograms/l, the frequency of phlebotomy should be reduced (4-12 per year). If the patient already has cirrhosis, the risk of HCC is very high.",adolescent;adult;biopsy;blood;child;chronic disease;comparative study;diabetes mellitus;differential diagnosis;fatty liver/di [Diagnosis];fatty liver/et [Etiology];genetics;hemochromatosis/co [Complication];hemochromatosis/di [Diagnosis];hemochromatosis/th [Therapy];human;liver;liver cirrhosis/co [Complication];middle aged;mutation;obesity/co [Complication];pathology;phlebotomy;review;risk factor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/an [Drug Analysis];chelating agent/dt [Drug Therapy];copper;ferritin;penicillamine/dt [Drug Therapy];transferrin/an [Drug Analysis],"Maier, K. P.",2002,27 Nov,,0,0,
2281,Wilson's disease and pregnancy [2],,Pregnancy;Wilson's disease;Zinc;adult;case report;clinical feature;controlled study;female;human;human tissue;laboratory test;letter;liver biopsy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfide/dt [Drug Therapy],"Moreno Planas, J. M.;Broseta Viana, L.;Herrero Quiros, C.;Calbo Mayo, J. M.;Garcia Rayo, M.;Perez Flores, R.",2002,,,0,0,
2282,Appropriate administration schedule of D-penicillamine for pediatric Wilson's disease patients based on urinary copper excretion. [Japanese],"The purpose of this study was to increase the amount of copper excreted resulting from the administration of D-penicillamine(DP) in pediatric Wilson's disease(WD) patients. By measuring the urinary copper excretion after adjusting the administration schedules, the appropriate timing for DP administration was investigated. The subjects were three brothers with pediatric WD. The initial daily dose of DP was 5 mg/kg/day, and gradual1y increased to the maintenance dose of 20 mg/kg/day. Until the maintenance daily dose was reached, DP was administered 2 h after the morning and evening meal. After reaching the maintenance daily dose of DP, the appropriate timing for taking DP was investigated in both the morning and evening. Three schedules of DP administration were compared: 2 h after meals; 30 min before meals (with fasting); and 1 h before the morning and l.5 before the evening meal (direction 1). The resulting urinary copper excretion on each dosing schedule was compared. Little difference was found in urinary copper excretion on the first two schedules, i. e., 2 h after meals and 30 min before meals. When DP was administered 30 min before meals, urinary copper excretion [mug/day] was 1173 in the first brother, 918 in the second, and 875 in the third. When DP was administered according to direction 1, however, urinary copper excretion was increased significantly to 1701 in the first brother, 2701 in the second, and 3808 in the third. It is known that the efficiency of urinary copper excretion with DP administration depends on the maintenance of chelating ability after absorption from the gastrointestinal tract. Our results indicate that the excretion was lower when DP was administered 2 h after or 30 min before meals (with fasting), as recommended in the package insert. Thus to achieve better copper excretion efficiency, direction 1 is recommended for WD patients. © 2002 The Pharmaceutical Society of Japan.",Administration schedule;D- penicillamine;Urinary copper excretion;Wilson's disease;absorption;article;case report;controlled study;dose calculation;drug dose regimen;gastrointestinal tract;human;infant;maintenance drug dose;male;statistical significance;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Fukuoka, N.;Morita, S.;Hamatani, S.;Okada, H.;Kondoh, M.;Imai, T.;Ohnishi, S.;Itoh, S.",2002,August,http://dx.doi.org/10.1248/yakushi.122.585,0,0,
2283,D-penicillamine-induced Elastosis perforans serpiginosa. [Italian],"Elastosis Perforans Serpiginosa (EPS) is an uncommon skin disease characterized by transepithelial elimination of abnormal dermal elastic fibers. This disease can be divided into three forms: idiopathic EPS; EPS associated with specific genetic connective tissue defects and D-penicillamine induced EPS after prolonged high dose therapy for Wilson's disease, cystinuria, rheumatoid arthritis. A 28 year-old man with Wilson's disease since he was 18 years-old and since that under prolonged treatment with D-penicillamine, noted the onset, two years ago, of multiple keratotic papules in serpiginous and annular pattern along the neck and on the righ arm respectively. Examination of biopsy specimens by light microscopy revealed the characteristic changes of EPS both idiopathic and D-penicillamine induced. Examination by transmission electron microscopy revealed characteristic changes of the elastic fibers of the D-penicillamine induced EPS never up till now described in idiopathic EPS. D-penicillamine is a life saving drug in the treatment of Wilson's disease, as a copper chelating agent, in spite of the well documented systemic and cutaneous unwanted effects produced. The pathogenic mechanism of the dermatopathy and how D-penicillamine induced the elastic fibers changes with their subsequent extrusion on the surface of the skin is unknown; some pathogenic hypotheses are suggested.","Adverse effects;Cutis laxa, etiology;Hepatolenticular degeneration, therapy;Penicillamine;adult;article;case report;clinical feature;cutis laxa/di [Diagnosis];cutis laxa/et [Etiology];cutis laxa/si [Side Effect];cystinuria/dt [Drug Therapy];dose response;elastic fiber;elastosis perforans serpiginosa/di [Diagnosis];elastosis perforans serpiginosa/et [Etiology];elastosis perforans serpiginosa/si [Side Effect];human;idiopathic disease;male;pathogenesis;rheumatoid arthritis/dt [Drug Therapy];skin biopsy;transmission electron microscopy;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy]","Pinna, A. L.;Ambu, R.;Atzori, L.;Aste, N.",2002,October,,0,0,
2284,Late presentation of Wilson's disease [3],,Age;Diagnosis;Wilson's disease;adult;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];case report;chromosome 13;clinical feature;gene mutation;human;letter;liver biopsy;liver fibrosis;male;proteinuria;vitamin supplementation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Santander Vaquero, C.",2002,August,,0,0,
2285,26-Year-old man with rapidly progressive jaundice and anemia,,abdominal pain;adult;anemia;article;case report;clinical feature;colonoscopy;differential diagnosis;drug efficacy;hematochezia;human;jaundice;laboratory test;liver failure;liver transplantation;male;physical examination;symptom;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Maple, Ii J. T.;Litin, S. C.",2002,,,0,0,
2286,The eye in Wilson's disease: Sunflower cataract associated with Kayser-Fleischer ring,,adult;article;cataract/co [Complication];ceruloplasmin blood level;clinical feature;female;human;human cell;neurologic disease/co [Complication];priority journal;tremor/co [Complication];Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Deguti, M. M.;Tietge, U. J. F.;Barbosa, E. R.;Cancado, E. L. R.",2002,01 Nov,http://dx.doi.org/10.1016/S0168-8278%2802%2900179-4,0,0,
2287,"Wilson's disease. Clinical presentation, treatment and evolution in 21 cases. [French]","Purpose - Wilson's disease is characterized by neuropsychiatric symptoms with frequent extrapyramidal and intellectual presentations. They have an insidious evolution that leads to a late diagnosis and less therapeutic effectiveness in the advanced forms. Methods - We report 21 cases of Wilson's disease with neurological complications, emphasizing clinical semiology, diagnostic means and problems of the therapeutics in our country. Results - The average age at the beginning of the disease was 17.6 years, with a female prevalence (8/13). The signs at first were mostly all neurological (71,4 %), then psychiatric (19 %) or hepatic (19 %). The most common neurological signs were dystonia of members (81 %), dysarthria (76 %), tremors (76 %) or disorders of motoricity (71,4 %). Sometimes there were sialorrhea or disorders of the handwriting. The Kayser-Fleischer ring was present in 19 patients. Eighteen patients had clinical and/or biological hepatic involvement. The diagnosis was confirmed by biochemical examinations, which found a low rate of copper in blood, a sinking rate of ceruloplasmin and a very high rate of urinary copper. The cerebral computer tomography shows a cortical and/or subcortical atrophy (37 %), and/or a low density of the central grey cores (35 %). The treatment was based on D-penicillamine and/or zinc sulfate, according to the availability of the drugs. The evolution was favourable among 18 patients (85 %) and not good in 42,8 % of the cases. Six of the first patients had poor evolution after many years of follow-up. Finally, only 12 patients (57 %) had a very good outcome. The family investigation made among 17 patients revealed 13 family cases. The only predictive factor of a poor evolution was the therapeutic noncompliance (P = 0.006). Conclusions - The neurological presentations are traditional during the Wilson's disease, but are often ignored. We must suspect the disease in children when faced with disorders of handwriting or school failures and in the adult, when faced with neurological symptoms in a patient having a hepatic disease. We must not hesitate to consider it even given purely psychiatric signs, and we had better know to seek the neurological ones. © 2002 Editions scientifiques et medicales Elsevier SAS.",Copper;Dystonia;Hepatolenticular degeneration;Kayser-fleischer ring;Liver cirrhosis;Wilson's disease;academic achievement;adolescent;adult;article;brain atrophy/co [Complication];brain atrophy/di [Diagnosis];clinical article;clinical feature;computer assisted tomography;copper blood level;diagnostic procedure;disease course;dysarthria/co [Complication];dystonia/co [Complication];eye disease/co [Complication];family study;female;follow up;handwriting;human;hypersalivation/co [Complication];kayser fleischer ring/co [Complication];liver disease/co [Complication];male;mental disease/co [Complication];motor dysfunction/co [Complication];neurologic disease/co [Complication];neurologic disease/di [Diagnosis];onset age;patient compliance;prevalence;prognosis;risk assessment;risk factor;sex ratio;symptom;symptomatology;treatment outcome;tremor/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];benserazide plus levodopa;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];trientine;trihexyphenidyl;zinc sulfate/cb [Drug Combination];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy],"Bono, W.;Moutie, O.;Benomar, A.;Aidi, S.;El Alaoui-Faris, M.;Yahyaoui, M.;Chkili, T.",2002,,http://dx.doi.org/10.1016/S0248-8663%2802%2900589-1,0,1,
2288,Zinc and copper in diseases of the digestive tract]. [Czech],"The author mentions the basic metabolic functions of zinc and copper in the human organism. She emphasizes the relationship of serious diseases, congenital and acquired, associated with deficiency or excess of these mineral trace elements. As to inborn diseases, we encounter most frequently Wilson's disease in impaired copper metabolism, rarely morbus Danbolt in congenital impairment of zinc absorption. In practice we are faced in particular with secondary causes of impaired zinc or copper levels, e.g. in chronic diarrhoeal conditions, coeliac disease, chronic pancreatitis and others.",disorders of metal metabolism/co [Complication];gastrointestinal disease/et [Etiology];human;metabolism;review;copper;zinc,"Zakova, A.",2002,Jan,,0,0,
2289,Current principles of Wilson's disease--diagnosis and treatment. [Polish],"Wilson's disease defined also as hepatolenticular degeneration is an important clinical problem of young adults still causing diagnostic difficulties. In the course of the last decade, genetic background of the disease has been definitely established and elucidated, confirming the variety of genetic mutations, responsible for its origin. The current scheme of the disease treatment has been elaborated and established. It aims to eliminate the excess of toxic copper ions from the organism as fast as possible. In the initial phase of the treatment, traditional and recently introduced chelating agents administration usually results in prompt tissue copper deposits excretion and copper metabolism balance maintenance. In the chronic therapy, zinc compounds, inducing intestinal and hepatic metallothionein synthesis, have been gaining more common application. Life-long, constant, pharmacological Wilson's disease therapy, administered after its early diagnosis, allows for long periods of patients survival, frequently comparable to the normal population.",adult;human;liver;metabolism;pathology;pathophysiology;quality of life;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];copper;zinc derivative/dt [Drug Therapy],"Najda, J.;Stella-Holowiecka, B.;Machalski, M.;Woszczyk, D.;Mykala-Ciesla, J.",2002,,,0,0,
2290,Copper metabolic defects and liver disease: Environmental aspects,"Copper (Cu) is an essential trace element for many biological processes. Cu homeostasis is generally well maintained by inbuilt controls in intestinal absorption, biliary excretion and intrahepatic storage. Copper deficiency disorders are rare. Acute Cu toxicity occurs occasionally in accidental poisoning with Cu sulfate. Chronic Cu toxicity in the form of liver cirrhosis and damage to other organs is seen classically in Wilson's Disease (genetic abnormality of Cu metabolism) and in the presumed environmental disorder Indian Childhood Cirrhosis (ICC). The clinical, epidemiological and treatment aspects of ICC are described. The evidence linking ICC to environmental Cu is (i) greatly increased hepatic Cu; (ii) early introduction of Cu contaminated milk boiled or stored in brass vessels; (iii) dramatic decline in ICC throughout the country coincident with change in feeding vessels; and (iv) continued long-term remission in D-penicillamine-treated patients after withdrawl of the drug. The nature and role of a second factor in the causation of ICC remains unclear, although a genetic predisposition is strongly suspected. Scattered reports of an ICC-like illness from the West (Idiopathic Cu Toxicosis, Endemic Tyrolean Infantile Cirrhosis), suggest that different mechanisms (environmental, genetic or both) can lead to the same end stage liver disease - 'ecogenetic' disorders. © 2002 Blackwell Publishing Asia Pty Ltd.",Copper;Environmental copper;Idiopathic copper toxicosis;Indian Childhood Cirrhosis;conference paper;copper deficiency;copper metabolism;drug withdrawal;environmental factor;high risk population;homeostasis;human;Indian childhood cirrhosis/dt [Drug Therapy];Indian childhood cirrhosis/pc [Prevention];intoxication;liver cirrhosis;priority journal;remission;sibling;survival;toxicity;treatment outcome;copper/ec [Endogenous Compound];copper sulfate/to [Drug Toxicity];penicillamine/dt [Drug Therapy],"Pandit, A. N.;Bhave, S. A.",2002,,http://dx.doi.org/10.1046/j.1440-1746.17.s3.35.x,0,0,
2291,Perspective study on effect of gandou tablet I on biliary trace elements in treating hepatolenticular degeneration. [Chinese],"OBJECTIVE: To observe the effect of gandou tablet I (GDI), a Chinese herbal recipe, on the content of biliary trace elements in hepatolenticular degeneration(HLD) patients. METHODS: Before and after 4 weeks treatment by oral taken GDI, bile of 32 cases of HLD were collected by duodenal drainage for determining biliary trace elements, including copper, zinc, iron and calcium, by spectrophotometer of atom absorption spectrum, and compared with those of 30 cases of non-HLD patients as the control. RESULTS: The contents of copper, iron and copper/zinc ratio were obviously lower, while the content of calcium greatly higher (P < 0.01), in the HLD group before GDI treatment than those in the control (P < 0.01 or P < 0.05), but the content of zinc was not significantly different between the two groups. The output of biliary copper after GDI treatment was significantly increased compared with that before treatment (P < 0.05), but the contents of zinc, iron, calcium and copper/zinc ratio were not markedly changed. CONCLUSION: The impediment to output of biliary copper was one of the mechanisms for copper storage in body of HLD patients. GDI could promote excretion of biliary copper in the HLD patients.",adolescent;adult;article;bile;child;female;human;male;metabolism;phytotherapy;prospective study;tablet;Wilson disease/dt [Drug Therapy];copper;herbaceous agent/dt [Drug Therapy];iron;trace element;zinc,"Hu, W. B.;Yang, R. M.",2001,Jul,,0,0,
2292,The hepatic form of Wilson's disease in young patients. [Czech],"Wilson's disease (WD) is a hereditary disorder of the copper metabolism with very varied clinical and biochemical symptoms. Hepatic and neurological forms are the most frequent manifestations of this rare disease. In schoolchildren and adolescents symptoms of liver damage predominate. In a retrospective study 19 patients were evaluated with biochemical signs of hepatopathy manifested before the age of 18 years. The diagnosis of WD was established at the age of 7 to 27 years. One female patient was admitted with fulminant hepatic failure which was treated by acute transplantation of the liver in the Institute of Clinical and Experimental Medicine in Prague. Only 9 of 18 patients with chronic hepatic affection at the time of diagnosis met the Sternlieb diagnostic criteria. These patients had reduced ceruloplasmin levels (0.08-0.18 g/l) and a high copper content in the hepatic dry matter (783 ug/g +/- 323 [SD]). In the remaining 9 patients the ceruloplasmin level was normal, however, in 8 a high copper content of the hepatic dry matter was found (696 ug/g (+)- 352[SD]. The last patient from this group had Kayser-Fleischer's (K-F) ring. It was possible to confirm the high copper content in the hepatic dry matter only after one year's penicillinamine treatment because at the time of the diagnosis poor coagulation did not permit to perform a liver biopsy. There was a statistically significant difference in the copper content of the hepatic dry matter in patients meeting and not meeting Sternlieb's criteria. Statistically significant differences between both groups were found in the plasma copper levels and in the 24-hour urinary copper excretion. Histological examination of the liver under a light microscope revealed findings from minimal changes associated with the presence of glycogen nuclei in hepatocytes to the picture of active chronic hepatitis. In all 19 patients the gene mutation H1069Q was examined and the results were positive in 39.8%. In 3 asymptomatic patients it was present in the homozygous form. CONCLUSION: Early detection of the atypical form of WD remains very difficult. The gold standard is still in all cases assessment of copper in the dry liver tissue. In the near future an important place will be held also by direct DNA analysis although its use is limited not only by the large number of known mutations but also by the financial costs of the method.",adolescent;adult;article;child;female;human;liver disease/di [Diagnosis];male;retrospective study;Wilson disease/di [Diagnosis],"Smolka, V.;Frysak, Z.;Kozak, L.;Mathonova, J.;Jezdinska, V.;Novak, Z.;Hrckova, Y.;Vrabelova, S.",2000,Jan,,0,0,
2293,Two recovery cases of Wilson's disease initiated with severe hemolysis and acute hepatic failure. [Japanese],,adolescent;article;case report;female;hemolytic anemia/et [Etiology];human;liver failure/et [Etiology];male;plasmapheresis;Wilson disease/co [Complication];Wilson disease/th [Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Takahashi, A.;Suzuki, T.;Shishido, S.;Tojo, J.;Ito, O.;Kazuta, Y.;Watanabe, H.;Ishikawa, H.;Ohira, H.;Obara, K.;Kasukawa, R.",2000,Jun,,0,0,
2294,Effect of gandou decoction on copper metabolism of skin fibroblast of hepatolenticular degeneration model. [Chinese],"OBJECTIVE: To explore the cytological mechanism of Gandou Decoction (GDD) in treating hepatolenticular degeneration (HLD). METHODS: Twenty-three in vitro models of cultured skin fibroblast of HLD were established to observe the intracellular change of microelements (Cu2+, Zn2+, etc.) content before and after adding rabbit's serum containing GDD. RESULTS: After being treated with GDD contained serum for 24 hours, the intracellular content of Cu2+ decreased from (80.94 +/- 34.76) ng/mg to (46.90 +/- 22.14) ng/mg, P < 0.01, while that of Zn2+ increased from (140.43 +/- 33.81) ng/mg to (151.43 +/- 37.83) ng/mg, P < 0.01. CONCLUSION: GDD is quite effective in removing the intracellular copper and increasing the intracellular zinc.",adolescent;adult;animal;article;cell culture;child;female;fibroblast;human;male;metabolism;pathology;rabbit;randomization;skin;Wilson disease;copper;herbaceous agent/pd [Pharmacology],"Tang, Q.;Yang, R.;Han, Y.",2000,Jan,,0,0,
2295,A case of delayed diagnosis of Wilson's disease. [Russian],,adult;article;case report;chronic hepatitis/di [Diagnosis];dementia/di [Diagnosis];dementia/et [Etiology];dose response;female;human;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Averkina, N. A.;Orlova, O. R.;Shariapova, R. B.",2000,,,0,0,
2296,Liver transplantation in a patient with hemolytic syndrome in the course of fulminant Wilson's disease. [Polish],"The case report of a 20 year old woman with fulminant liver failure and hemolytic syndrome was described. Huge amounts of copper excreted in the urine (3555 mg/12 h without, and 5180 mg/12 h after d-penicillamine provocation, respectively) confirmed the diagnosis of fulminant Wilson's disease. Because the patient's general condition worsened rapidly (hemolysis, diathesis hemorrhagic, ascites, encephalopathy increased during 3 days of clinical observation) orthotopic liver transplantation was performed. After the transplantation, ischemic type biliary lesion (ITBL) II stage was diagnosed. The woman is still being treated with Prograf and Urso-Falk. The patient returned to her normal life, continues to work and was married. Two years after OLT she gave birth to a healthy boy. The liver function tests are normal with the exception of GGTP and FALK activities elevation. Copper and ceruloplasmin level, as well as copper excretion in the urine are within the normal values.",adult;article;case report;female;hemolytic uremic syndrome/et [Etiology];hemolytic uremic syndrome/su [Surgery];human;liver failure/et [Etiology];liver failure/su [Surgery];liver transplantation;remission;urine;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];copper,"Dabrowska, E.;Jablonska-Kaszewska, I.;Ozieblowski, A.;Porzezinska, B.;Falkiewicz, B.",2000,,,0,0,
2297,"Gall stones, G-6PD deficiency and Wilson's disease",,case report;chelation therapy;child care;clinical feature;disease association;disease course;disease predisposition;family history;gallstone/di [Diagnosis];gallstone/dt [Drug Therapy];genetic predisposition;glucose 6 phosphate dehydrogenase deficiency/di [Diagnosis];human;incidence;letter;liver function test;male;physical examination;prothrombin time;risk assessment;risk factor;school child;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy];albumin/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];glucose 6 phosphate dehydrogenase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Singh, R.;Sibal, A.;Jain, S. K.",2002,,,0,0,
2298,Hepatic copper concentration in children undergoing living related liver transplantation due to Wilsonian fulminant hepatic failure,"Liver transplantation is indicated for Wilson's disease (WD) patients having the fulminant form and end-stage liver failure. To evaluate whether living related liver transplantation (LRLT) can correct the copper metabolism in WD patients, we studied two children who underwent LRLT because of fulminant hepatic failure. They were 7 and 13 yrs old at the time LRLT was performed. Serum ceruloplasmin levels, serum copper levels, copper urine excretion, and hepatic copper concentrations were measured. Serum ceruloplasmin levels (16.7 +/- 1.2 mg/dL) and serum copper levels (67.0 +/- 1.4 mug/dL) were lower than the normal range after LRLT in case 1. In both patients, urinary copper excretion was reduced markedly after LRLT, but was not normalized (case 1, 191.2 +/- 182.2 mug/d; case 2, 140.0 +/- 156.7 mug/d). Hepatic copper concentrations were slightly elevated (case 1, 158.8 +/- 44.6 mug/g dry weight; case 2, 147.0 mug/g dry weight) after LRLT in both cases, but did not exceed 250 mug/g dry weight. LRLT is a curative procedure in Wilson's disease presenting fulminant hepatic failure or advanced cirrhosis. However, this study indicates that the conditions of copper metabolism in WD patients undergoing LRLT are similar to those in heterozygous genetic carriers. Because the living related donors are the parents who carry the abnormal gene, LRLT cannot completely restore the copper balance in WD patients.",Ceruloplasmin;Copper metabolism;Hepatic copper;Heterozygote;Liver biopsy;adolescent;article;case report;ceruloplasmin blood level;controlled study;copper blood level;dry weight;female;human;human tissue;liver cirrhosis/co [Complication];liver cirrhosis/su [Surgery];liver failure/dt [Drug Therapy];liver failure/su [Surgery];liver level;liver transplantation;living donor;parent;priority journal;school child;side effect/si [Side Effect];urinary excretion;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];tacrolimus/po [Oral Drug Administration],"Komatsu, H.;Fujisawa, T.;Inui, A.;Sogo, T.;Sekine, I.;Kodama, H.;Uemoto, S.;Tanaka, K.",2002,,http://dx.doi.org/10.1034/j.1399-0012.2002.01074.x,0,0,
2299,Wilson's disease with neuropsychiatric manifestations and liver disease but no Kayser-Fleischer ring [4],,adult;case report;clinical feature;echography;gonioscopy;human;letter;liver cirrhosis/co [Complication];male;mental disease/co [Complication];neurologic disease/co [Complication];nuclear magnetic resonance imaging;priority journal;slit lamp;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Makharia, G. K.;Nandi, B.;Garg, P. K.;Tandon, R. K.",2002,,http://dx.doi.org/10.1097/00004836-200207000-00025,0,0,
2300,Wilson's disease. [Spanish],"Wilson's disease is an inherited disorder of copper metabolism. It usually presents during the 2<sup>nd</sup> and 3<sup>rd</sup> decades with a prevalence of 1:40.000. Its transmission as an autosomal-recessive disease is linked to the ATP7B gene, located on chromosome 13q14.3-q21.1. It begins with neurological, psychiatric or hepatic symptoms and can also affect other systems. Laboratory testing show high serum free copper, as well as high 24-hour urinary copper excretion and a decreased serum ceruloplasmin. Brain scans show putamen abnormalities. Liver biopsy with high copper levels is sometimes necessary to confirm de diagnosis. Its treatment is based on a low dietary copper intake and drugs like penicillamine, zinc, trientine and tetrathiomolybdate. Cases with severe hepatic failure respond to liver transplantation. Not treated patients die, due to hepatic dysfunction and severe neurological deterioration. Treatment can control copper toxicity and revert symptoms, specially when administered early. It is essential the diagnostic testing of close relatives. Treatment must continue for lifetime.",Ceruloplasmin;Chromosome 13;Copper;Movement disorders;Penicillamine;Zinc;aplastic anemia/si [Side Effect];ATP7B gene;autosomal recessive disorder;brain tomography;ceruloplasmin blood level;cholestasis/si [Side Effect];chromosome 13q;clinical feature;copper metabolism;diet therapy;disease severity;disease transmission;drug eruption/si [Side Effect];early diagnosis;gene;Goodpasture syndrome/si [Side Effect];human;inheritance;leukopenia/si [Side Effect];liver disease;liver failure/su [Surgery];liver transplantation;lymphadenopathy/si [Side Effect];mental disease;motor dysfunction;neurologic disease;poliomyelitis/si [Side Effect];prevalence;review;systemic lupus erythematosus/si [Side Effect];thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];prednisone;tetrathiomolybdic acid/dt [Drug Therapy];trientine/do [Drug Dose];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Giannaula, R. J.",2002,June,,0,0,
2301,Inherited metabolic disease,"The elucidation of metabolic pathways and the genetic basis for diseases of the liver continues to increase our understanding of disease pathogenesis and advance treatment options. This selective review covers a wide range of subjects, from the identification of novel proteins and the importance of specific transport pathways to phenotypic expression of disease and management of acute liver failure. Three selected disorders - Wilson disease, genetic hemochromatosis and other hereditary iron overload disorders, and alpha<inf>1</inf>-antitrypsin disease - are the focus of this review. ©2002 Lippincott Williams & Wilkins, Inc.",alpha 1 antitrypsin deficiency/su [Surgery];gastrointestinal toxicity/si [Side Effect];genetic disorder;hemochromatosis;human;iron overload;liver failure;liver transplantation;metabolic disorder/dt [Drug Therapy];metabolic disorder/su [Surgery];metabolism;nonhuman;pathogenesis;review;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Schilsky, M. L.",2002,,http://dx.doi.org/10.1097/00001574-200205000-00003,0,0,
2302,Understanding the mechanism and function of copper P-type ATPases,,binding site;catalysis;gene mutation;human;Menkes syndrome;Michaelis Menten kinetics;nonhuman;oxidation reduction reaction;priority journal;regulatory mechanism;review;site directed mutagenesis;transport and binding phenomena;Wilson disease/dt [Drug Therapy];adaptor protein/ec [Endogenous Compound];adenosine triphosphatase/ec [Endogenous Compound];amino acid/ec [Endogenous Compound];binding protein/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chaperone/ec [Endogenous Compound];copper;heavy metal/to [Drug Toxicity];orthovanadic acid;penicillamine/dt [Drug Therapy];phosphate;protein/ec [Endogenous Compound],"Voskoboinik, I.;Camakaris, J.;Mercer, J. F. B.",2002,,http://dx.doi.org/10.1016/S0065-3233%2802%2960053-1,0,0,
2303,Pulmonary-renal syndromes in the intensive care unit,"Renal disease associated with pulmonary hemorrhage is seen in a variety of clinical disorders and is a common cause of admission to intensive care units. Recent advances in the understanding of the pathogenesis of these disorders have improved the therapeutic options significantly and have favorably influenced the course of many of these disorders. This article discusses rheumatologic diseases that involve both the kidney and lungs, with emphasis on pathogenesis and therapeutic options. Common pulmonary-renal syndrome including anti-glomerular basement membrane disease and anti-neutrophil cytoplasmic autoantibodies-associated vasculitis.",azoospermia/si [Side Effect];bone marrow toxicity/si [Side Effect];cancer risk;clinical feature;diet supplementation;differential diagnosis;disease predisposition;environmental factor;focal glomerulonephritis;Goodpasture syndrome/di [Diagnosis];Goodpasture syndrome/dt [Drug Therapy];Goodpasture syndrome/et [Etiology];Goodpasture syndrome/th [Therapy];human;hypertension/co [Complication];hypertension/dt [Drug Therapy];intensive care unit;kidney biopsy;kidney disease/di [Diagnosis];kidney disease/dt [Drug Therapy];kidney disease/et [Etiology];kidney disease/su [Surgery];kidney disease/th [Therapy];kidney graft;laboratory diagnosis;leukopenia/si [Side Effect];lung disease/di [Diagnosis];lung disease/dt [Drug Therapy];lung disease/et [Etiology];lung disease/th [Therapy];lung hemorrhage/si [Side Effect];osteoporosis/si [Side Effect];pathogenesis;plasmapheresis;priority journal;pulmonary renal syndrome/di [Diagnosis];pulmonary renal syndrome/dt [Drug Therapy];pulmonary renal syndrome/et [Etiology];pulmonary renal syndrome/su [Surgery];pulmonary renal syndrome/th [Therapy];recurrent disease;review;small vessel vasculitis/di [Diagnosis];small vessel vasculitis/dt [Drug Therapy];small vessel vasculitis/et [Etiology];small vessel vasculitis/su [Surgery];small vessel vasculitis/th [Therapy];transitional cell carcinoma;treatment outcome;Wegener granulomatosis/di [Diagnosis];Wegener granulomatosis/dt [Drug Therapy];Wegener granulomatosis/et [Etiology];Wegener granulomatosis/th [Therapy];Wilson disease/dt [Drug Therapy];azathioprine/ae [Adverse Drug Reaction];azathioprine/dt [Drug Therapy];azathioprine/po [Oral Drug Administration];calcium/dt [Drug Therapy];calcium/po [Oral Drug Administration];CD20 antigen;cotrimoxazole/dt [Drug Therapy];cyclophosphamide/ae [Adverse Drug Reaction];cyclophosphamide/dt [Drug Therapy];cyclophosphamide/iv [Intravenous Drug Administration];cyclophosphamide/po [Oral Drug Administration];dipeptidyl carboxypeptidase inhibitor/dt [Drug Therapy];immunoglobulin/dt [Drug Therapy];immunoglobulin/iv [Intravenous Drug Administration];interleukin 2 receptor;interleukin 2 receptor blocking agent/dt [Drug Therapy];methylprednisolone/ae [Adverse Drug Reaction];methylprednisolone/do [Drug Dose];methylprednisolone/dt [Drug Therapy];methylprednisolone/iv [Intravenous Drug Administration];monoclonal antibody/dt [Drug Therapy];monoclonal antibody cd20/dt [Drug Therapy];neutrophil cytoplasmic antibody/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prednisone/ae [Adverse Drug Reaction];prednisone/dt [Drug Therapy];prednisone/po [Oral Drug Administration];receptor blocking agent/dt [Drug Therapy];unclassified drug;vitamin D/dt [Drug Therapy];vitamin D/po [Oral Drug Administration],"Rodriguez, W.;Hanania, N.;Guy, E.;Guntupalli, J.",2002,November,http://dx.doi.org/10.1016/S0749-0704%2802%2900029-5,0,0,
2304,Introducing Wilson disease mutations into the zinc-transporting P-type ATpase of Escherichia coli: The mutation P634L in the 'hinge' motif (GDGXNDXP) perturbs the formation of the E<inf>2</inf>P state,"ZntA, a bacterial zinc-transporting P-type ATPase, is homologous to two human ATPases mutated in Menkes and Wilson diseases. To explore the roles of the bacterial ATPase residues homologous to those involved in the human diseases, we have introduced several point mutations into ZntA. The mutants P401L, D628A and P634L correspond to the Wilson disease mutations P992L, D1267A and P1273L, respectively. The mutations D628A and P634L are located in the C-terminal part of the phosphorylation domain in the so-called hinge motif conserved in all P-type ATPases. P401L resides near the N-terminal portion of the phosphorylation domain whereas the mutations H475Q and P476L affect the heavy metal ATPase-specific HP motif in the nucleotide binding domain. All mutants show reduced ATPase activity corresponding 0-37% of the wild-type activity. The mutants P401L, H475Q and P476L are poorly phosphorylated by both ATP and P<inf>i</inf>. Their dephosphorylation rates are slow. The D628A mutant is inactive and cannot be phosphorylated at all. In contrast, the mutant P634L six residues apart in the same domain shows normal phosphorylation by ATP. However, phosphorylation by P<inf>i</inf> is almost absent. In the absence of added ADP the P634L mutant dephosphorylates much more slowly than the wild-type, whereas in the presence of ADP the dephosphorylation rate is faster than that of the wild-type. We conclude that the mutation P634L affects the conversion between the states E<inf>1</inf>P and E<inf>2</inf>P so that the mutant favors the E<inf>1</inf> or E<inf>1</inf>P state.",Heavy metal transport;Hinge motif;Ion translocation;P-type ATPase;Wilson disease mutation;amino terminal sequence;article;bacterial gene;carboxy terminal sequence;controlled study;enzyme activity;enzyme specificity;Escherichia coli;gene mutation;genetic conservation;nonhuman;point mutation;priority journal;protein dephosphorylation;protein domain;protein function;protein motif;sequence homology;Wilson disease;adenosine triphosphatase/ec [Endogenous Compound];isoenzyme/ec [Endogenous Compound];zinc,"Okkeri, J.;Bencomo, E.;Pietila, M.;Haltia, T.",2002,,http://dx.doi.org/10.1046/j.1432-1033.2002.02810.x,0,0,
2305,Sleep in patients with treated Wilson's disease. A questionnaire study,"Objective: To examine general sleep habits and sleep disturbances among patients with treated Wilson's disease (WD), and in comparison with an age- and sex-matched reference group (RG). Methods: Twenty-four patients with WD with a mean (+/- s) age of 35.1 +/- 8.7 years and a disease duration of 17.7 +/- 5.1 years were investigated using a standardized sleep questionnaire comprising 87 questions concerning sleep habits, sleeping difficulties, demographic and lifestyle variables. The results were compared with those from a random sample of 72 individuals. Results: There was no significant difference in sleep time during the night, but WD patients had a significantly greater number of nocturnal awakenings compared with the RG. Fifty-nine per cent of the WD patients reported frequently being awake for more than 30 min during the night. Number of nocturnal awakenings was correlated to nightmares and palpitations only in the WD group. WD patients complained significantly more often than the RG over not feeling rested after sleep, taking frequent naps and fatigue during the daytime. Moreover, sleep paralysis and cataplexy occurred more often in the WD patients than in the RG. Conclusion: The sleep pattern of patients with treated WD differed from that of the reference group. The spectrum of reported symptoms by patients with treated WD suggests an altered REM sleep function. Future studies with objective methods are required to elucidate the mechanisms involved.",Hepatolenticular degeneration;Sleep;Sleep paralysis;Wilson's disease;adult;aged;arousal;article;cataplexy;clinical article;controlled study;demography;disease duration;fatigue;female;heart palpitation;human;lifestyle;male;night sleep;nightmare;parasomnia;questionnaire;REM sleep;rest;sleep disorder;sleep pattern;sleep time;standardization;symptom;Wilson disease/dt [Drug Therapy];flupentixol;nefazodone;penicillamine/dt [Drug Therapy];psychotropic agent;trientine/dt [Drug Therapy];venlafaxine;zinc acetate/dt [Drug Therapy],"Portala, K.;Westermark, K.;Ekselius, L.;Broman, J. E.",2002,,http://dx.doi.org/10.1080/08039480260242796,0,0,
2306,"Denny-Brown, Wilson's disease, and BAL (British antilewisite [2,3-dimercaptopropanol])",In 1951 Denny-Brown and Porter described the successful treatment of Wilson's disease using the chelating agent British antilewisite. The presentation of their results both at meetings and in print changed the traditional view of neurology from a descriptive to an interventional discipline using treatments based on the underlying biochemical disorder. The authors review the importance of these reports and provide edited digital versions of the films Denny-Brown made of the five patients described in the initial reports.,chelation;clinical feature;clinical trial;history of medicine;human;medical society;motor dysfunction;pathogenesis;priority journal;sensory neuropathy/dt [Drug Therapy];short survey;treatment outcome;voluntary movement;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];dimercaprol/ct [Clinical Trial];dimercaprol/dt [Drug Therapy];dimercaprol/im [Intramuscular Drug Administration];penicillamine/dt [Drug Therapy],"Vilensky, J. A.;Robertson, W. M.;Gilman, S.",2002,24 Sep,,0,0,
2307,Clinical approach to children with suspected neurodegenerative disorders,"Inherited neurodegenerative disorders are common in the Kingdom of Saudi Arabia as a result of the high rate of consanguinity. This is a complex field with a multitude of different disorders characterized by a variety of clinical manifestations, complex molecular biology, and a long list of potential investigations. As a result, this is often a confusing and difficult area for non-specialists, resulting in delays in reaching the diagnosis. Reaching a specific diagnosis is of clear importance for providing appropriate therapy, prognosis, and genetic counseling. This paper is intended to provide a simplified practical approach to guide residents and generalists in the initial diagnostic evaluation of children with suspected neurodegenerative disorders. Emphasis is placed on useful clinical signs, diagnostic tips, potential pitfalls, and recent advances in therapy.",Child;Degenerative;Diagnosis;Evaluation;Inherited;Nervous system;adrenoleukodystrophy/dt [Drug Therapy];adrenoleukodystrophy/th [Therapy];anamnesis;childhood disease/di [Diagnosis];childhood disease/dt [Drug Therapy];childhood disease/th [Therapy];clinical feature;consanguinity;degenerative disease/di [Diagnosis];degenerative disease/dt [Drug Therapy];degenerative disease/th [Therapy];diagnostic test;encephalomyopathy/dt [Drug Therapy];eye disease/di [Diagnosis];eye disease/et [Etiology];Fabry disease/dt [Drug Therapy];genetic disorder/di [Diagnosis];genetic disorder/dt [Drug Therapy];genetic disorder/th [Therapy];globoid cell leukodystrophy/th [Therapy];human;Lesch Nyhan syndrome/dt [Drug Therapy];Menkes syndrome/dt [Drug Therapy];metachromatic leukodystrophy/th [Therapy];mucopolysaccharidosis/dt [Drug Therapy];mucopolysaccharidosis/th [Therapy];Refsum disease/th [Therapy];review;Saudi Arabia;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];allopurinol/dt [Drug Therapy];alpha galactosidase/dt [Drug Therapy];carnitine/dt [Drug Therapy];copper sulfate/dt [Drug Therapy];dichloroacetic acid/dt [Drug Therapy];erucic acid/dt [Drug Therapy];glyceryl trioleic acid/dt [Drug Therapy];levo iduronidase/dt [Drug Therapy];nicotinamide/dt [Drug Therapy];oleic acid/dt [Drug Therapy];penicillamine/dt [Drug Therapy];recombinant alpha galactosidase/dt [Drug Therapy];recombinant levo iduronidase/dt [Drug Therapy];riboflavin/dt [Drug Therapy];steroid/dt [Drug Therapy];trierucic acid/dt [Drug Therapy];ubidecarenone/dt [Drug Therapy];unclassified drug;zinc acetate/dt [Drug Therapy],"Jan, M. M.",2002,January,,0,0,
2308,The indication for liver transplant to improve neurological symptoms in a patient with Wilson's disease [1],,adult;ataxia;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/su [Surgery];bradykinesia;brain;case report;clinical feature;conservative treatment;copper blood level;disease course;dysarthria;dysphagia;dystonia;extrapyramidal symptom;human;letter;liver;liver failure/su [Surgery];liver transplantation;motor dysfunction;neurology;nuclear magnetic resonance imaging;priority journal;symptomatology;treatment outcome;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology],"Hermann, W.;Eggers, B.;Wagner, A.",2002,01 Dec,http://dx.doi.org/10.1007/s00415-002-0867-1,0,0,
2309,Cardiac involvement in Wilson disease,"Background: Wilson disease is an inherited autosomal recessive disorder of copper metabolism resulting in pathological accumulation of copper in the liver, brain and other tissues. One of the reported manifestations is cardiac involvement. Methods: We studied 42 patients with Wilson disease (19 men and 23 women, mean age 34+/-10 y) and 42 age- and sex-matched healthy volunteers. All subjects underwent complete echocardiographic examination; 24h ECG Holter monitoring was performed in 23 Wilson disease patients. Results: In comparison to healthy subjects, patients with Wilson disease had increased thickness of the interventricular septum (9.5+/-1.4 vs 8.6+/-1.1 mm, p < 0.01) and left ventriclular (LV) posterior wall (9.1+/-1.3 vs 8.2+/-1.0 mm, p < 0.01). While the two groups did not differ in LV mass index, relative LV wall thickness was significantly increased in Wilson disease patients compared to control subjects (0.39+/-0.06 vs 0.34+/-0.04 p < 0.001). Concentric LV remodelling was present in 9 patients (21%) and LV hypertrophy in one patient. Systolic LV function showed a nonsignificant trend towards lower values in Wilson disease patients (EF 62+/-5% vs 64+/-5%, p = 0.06). Diastolic filling and the frequency of valvular abnormalities were comparable in both groups. The established echocardiographic abnormalities did not correlate with the type of Wilson disease manifestation, the presence of the His1069G1n mutation, laboratory parameters or the duration and type of therapy. Twenty-four-hour ECG Holter monitoring detected ECG abnormalities in 10 patients (42%), the most frequent findings being runs of supraventricular tachycardias and frequent supraventricular ectopic beats. Conclusions: Cardiac involvement in Wilson disease patients was mild, characterized by LV parietal thickening with an increased prevalence of concentric LV remodelling and a relatively high frequency of benign supraventricular tachycardias and extrasystolic beats.",adult;article;autosomal recessive inheritance;bioaccumulation;brain tissue;clinical article;controlled study;copper metabolism;disease severity;female;gene mutation;heart disease/di [Diagnosis];heart left ventricle filling;heart left ventricle hypertrophy;heart left ventricle mass;heart ventricle septum;heart ventricle wall;Holter monitoring;human;liver;male;supraventricular premature beat/di [Diagnosis];supraventricular tachycardia/di [Diagnosis];valvular heart disease;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;histidine/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Hlubocka, Z.;Marecek, Z.;Linhart, A.;Kejrova, E.;Pospisilova, L.;Martasek, P.;Aschermann, M.",2002,August,http://dx.doi.org/10.1023/A:1016546223327,0,0,
2310,Pregnancy and inherited metabolic disorders: Maternal and fetal complications,"Some inherited metabolic disorders (IMDs) can cause significant complications during pregnancy, affecting the mother and/or the fetus. Although it appears that only a minority of IMDs have these effects, experience is still being acquired. For some disorders, patients will not have reached child-bearing age. Pregnancies in this group of patients will increase as the management of IMDs in childhood and adolescence improves. Clinicians should be aware of potential complications and consider carefully how best to manage these conditions. Ideally, patients should be followed up in adult life by a specialized clinical team, which can implement a planned approach to conception and pregnancy, but often this is not possible. For disorders where the risk of complications is well established (e.g. phenylketonuria), optimal treatment may lead to a good fetal and maternal outcome. It is important also to consider the possibility of an IMD being present in fetuses of pregnancies that are affected by non-immune hydrops, maternal HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) or acute fatty liver of pregnancy.",adolescence;conception;cystinosis/dt [Drug Therapy];cystinuria/dt [Drug Therapy];drug safety;fatty acid oxidation;fatty liver;fetus development;fetus outcome;follow up;galactosemia;glycogen storage disease;HELLP syndrome;hereditary fructose intolerance;high risk population;histidinemia;homocystinuria/dt [Drug Therapy];human;hydrops;hyperprolinemia;maple syrup urine disease;metabolic disorder/dt [Drug Therapy];methylmalonic aciduria;phenylketonuria;pregnancy;priority journal;propionic acidemia;review;risk factor;tyrosinemia/dt [Drug Therapy];urea cycle;Wilson disease/dt [Drug Therapy];arylbutyric acid derivative/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];betaine/dt [Drug Therapy];cyclohexane derivative/dt [Drug Therapy];cystafos/dt [Drug Therapy];mercaptamine/dt [Drug Therapy];nitisinone/dt [Drug Therapy];penicillamine/dt [Drug Therapy];sodium phenylbutyrate/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;zinc/dt [Drug Therapy],"Preece, M. A.;Green, A.",2002,September,http://dx.doi.org/10.1258/000456302320314458,0,0,
2311,Managing liver failure,"Liver disease is rare in childhood, but important new developments have altered the natural history and outcome. It is important that clinicians are aware of these diseases and their management. Acute liver failure is most often due to viral hepatitis, paracetamol overdose, or inherited metabolic liver disease. The clinical presentation includes jaundice, coagulopathy, and encephalopathy. Early diagnosis is necessary to prevent complications such as cerebral oedema, gastrointestinal bleeding, and renal failure. Early supportive management, in particular intravenous N-acetylcysteine, may be effective but liver transplantation is usually the definitive treatment and thus early referral to a specialist unit for liver transplantation is mandatory. Chronic liver failure may be due to unresolved neonatal liver disease, either inherited biliary hypoplasia or extrahepatic biliary atresia, while in older children, autoimmune liver disease or cystic fibrosis are the commonest causes. Treatment includes specific medication, nutritional support, and liver transplantation, which now has a 90% survival with good quality life.",autoimmune hepatitis/dt [Drug Therapy];autoimmune hepatitis/su [Surgery];autoimmune hepatitis/th [Therapy];bile duct atresia;biliary tract disease;blood clotting disorder;brain disease/si [Side Effect];brain edema/co [Complication];child;child care;clinical feature;cystic fibrosis/th [Therapy];differential diagnosis;disease course;disease exacerbation/si [Side Effect];early diagnosis;esophagus varices/et [Etiology];esophagus varices/su [Surgery];esophagus varices/th [Therapy];fluid balance;gastrointestinal hemorrhage/co [Complication];graft rejection/co [Complication];hemochromatosis/dt [Drug Therapy];hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];human;intensive care;intrahepatic cholestasis/dt [Drug Therapy];intrahepatic cholestasis/su [Surgery];jaundice;kidney failure/co [Complication];liver failure/di [Diagnosis];liver failure/dt [Drug Therapy];liver failure/et [Etiology];liver failure/su [Surgery];liver failure/th [Therapy];liver transplantation;metabolic disorder;nutritional support;patient referral;quality of life;review;sclerotherapy;sepsis;survival rate;treatment indication;treatment outcome;virus hepatitis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];acetylcysteine/dt [Drug Therapy];amoxicillin/dt [Drug Therapy];carbamazepine/ae [Adverse Drug Reaction];cephalosporin/dt [Drug Therapy];corticosteroid/ae [Adverse Drug Reaction];corticosteroid/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];fluconazole/dt [Drug Therapy];halothane/ae [Adverse Drug Reaction];hepatitis B vaccine/dt [Drug Therapy];isoniazid/ae [Adverse Drug Reaction];lactulose/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];prostaglandin E1/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];pyridoxine/po [Oral Drug Administration];ranitidine/dt [Drug Therapy];selenium/dt [Drug Therapy];sucralfate/dt [Drug Therapy];tocofersolan/dt [Drug Therapy];trimethoprim/dt [Drug Therapy];valproic acid/ae [Adverse Drug Reaction];vitamin K group/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Kelly, D. A.",2002,01 Nov,http://dx.doi.org/10.1136/pmj.78.925.660,0,0,
2312,Peripheral nociceptin level in Wilson's disease patients. [Hungarian],"Plasma level of nociceptin, the endogenous agonists of orphaninFQ/OP4 receptor was found to be siginificantly elevated in Wilson's disease patients (14,87 +/- 2,44 pg/ml +/- SD, p < 0,001, n = 21) compared to age-matched healthy controls (9,18 +/- 1,63 pg/ml +/- SD, n = 25). Wilson's disease is an autosomal recessive disorder caused by mutation of the gene ATP7B leading to toxic copper accumulation mainly in the liver and brain and in other organs such as, kidney and cornea. Measurements were performed by <sup>125</sup>I -radioimmunoassay. Neither sex differences nor correlation between plasma nociceptin levels and liver function test results were found in Wilson's disease patients. It is suggested that significantly elevated plasma nociceptin level is due to the inhibition of nociceptin-inactivating Zn-metallopeptidases (aminopeptidase N, endopeptidase 24.15) by the toxic copper levels, as it is known that changing the central Zn atom to Cu results in an approximately 50% inhibition in the activity of these enzymes. The high plasma nociceptin level in Wilson's disease patients may induce significant impairment in nociceptinerg neurotransmission.",adult;article;ATP7B gene;autosomal recessive disorder/et [Etiology];brain disease;clinical article;cornea disease;correlation analysis;enzyme activity;female;gene;gene mutation;human;human tissue;kidney disease;liver disease;male;neurotransmission;radioimmunoassay;Wilson disease/et [Etiology];copper;iodine 125;metalloproteinase;microsomal aminopeptidase;nociceptin/ec [Endogenous Compound];nociceptin receptor/ec [Endogenous Compound];proteinase;zinc,"Beatrix, H. M.;Kornelia, T.;Ferenc, E. S.",2002,,,0,0,
2313,"Reduction of copper and metallothionein in toxic milk mice by tetrathiomolybdate, but not deferiprone","Copper is both essential for life and toxic. Aberrant regulation of copper at the level of intracellular transport has been associated with inherited diseases, including Wilson's disease (WND) in humans. WND results in accumulation of copper and the copper and zinc-binding protein metallothionein (MT) in liver and other tissues, liver degeneration, and neurological dysfunction. The toxic milk (TX) mutation in mice results in a phenotype that mimics human WND, and TX has been proposed to be a model of the disease. We characterized TX mice as a model of altered metal ion and MT levels during development, and after treatment with the metal ion chelators tetrathiomolybdate (TTM) and deferiprone (L1). We report that hepatic, renal and brain copper and MT are elevated in TX mice at 3 and 12 months of age. Zinc was significantly higher in TX mouse liver, but not brain and kidney, at both time points. Nodules appeared spontaneously in TX mouse livers at 8-12 months that maintained high copper levels, but with more normal morphology and decreased MT levels. Treatment of TX mice with TTM significantly reduced elevated hepatic copper and MT. Transient increases in blood and kidney copper accompanied TTM treatment and indicated that renal excretion was a significant route of removal. Treatment with L1, on the other hand, had no effect on liver or kidney copper and MT, but resulted in increased brain copper and MT levels. These data indicate that TTM, but not L1, may be useful in treating diseases of copper overload including WND. © 2002 Elsevier Science B.V. All rights reserved.",Copper;Deferiprone;Tetrathiomolybdate;Toxic milk mouse;Wilson's disease;animal tissue;brain level;conference paper;controlled study;copper blood level;development;drug effect;female;liver level;liver nodule;male;milk;morphology;mouse;mutation;newborn;nonhuman;phenotype;reduction;urinary excretion;Wilson disease;copper/ec [Endogenous Compound];deferiprone/cm [Drug Comparison];deferiprone/pd [Pharmacology];iron/ec [Endogenous Compound];metal ion/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/ip [Intraperitoneal Drug Administration];tetrathiomolybdic acid/pd [Pharmacology];zinc ion/ec [Endogenous Compound],"Czachor, J. D.;Cherian, M. George;Koropatnick, J.",2002,15 Jan,http://dx.doi.org/10.1016/S0162-0134%2801%2900383-X,0,0,
2314,Presymptomatic diagnosis of Wilson disease associated with a novel mutation of the ATP7B gene,We report a family study of a presymptomatic form of Wilson disease. Our report demonstrates that mutation analysis is very useful for diagnosing presymptomatic Wilson disease in patients without consanguineous parents and for assessing the carrier status of the patients' family members. Previously undetected mild cases of Wilson disease could be diagnosed using this methodology.,adolescent;allele;article;case report;cell degeneration;clinical feature;consanguinity;disease course;exon;gene mutation;genetic analysis;heterozygosity;human;laboratory test;liver biopsy;liver cell;liver function test;male;physical examination;polymerase chain reaction;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Ohya, K.;Abo, W.;Tamaki, H.;Sugawara, C.;Endo, T.;Nomachi, S.;Fukushi, M.;Kinebuchi, M.;Matsuura, A.",2002,,http://dx.doi.org/10.1007/s00431-001-0865-9,0,0,
2315,Roles of metallothionein in copper homeostasis: Responses to Cu-deficient diets in mice,"Metallothionein (MT) protects the body from both harmful non-essential and excessive essential metals. Copper (Cu) is an essential metal, and its concentration in the body is regulated at a constant level between excess and deficient ones. Cu accumulating in the livers of Wilson disease patients and its animal model, Long-Evans rats with a cinnamon-like coat color (LEC) rats, is in the form of Cu,Zn-MT, MT being an antioxidant. Contrary to the efficient production of MT in response to excessive accumulation of Cu in LEC rats, Cu-binding to MT only occurs marginally under normal conditions. However, the present study revealed that Cu binds to MT more with a severe Cu-deficiency. Namely, male C57BL/6J mice were fed a Cu-deficient diet (0.037 mg Cu/g) and deionized water containing trientine, and then the concentration and distribution of Cu were determined. It was suggested that the cessation of biliary excretion and limitation of the Cu supply to ceruloplasmin are the first responses on feeding of a Cu-deficient diet, followed by an increase in Cu-MT with maintenance of the Cu concentration in the liver. These results suggest that MT causes the recruitment of Cu in a Cu-deficient environment by sequestering Cu from degraded Cu-enzymes and delivering it to Cu chaperones. © 2002 Elsevier Science B.V. All rights reserved.","Ceruloplasmin;Copper;Copper chaperone;Copper deficiency;Copper,zinc-superoxide dismutase;Metallothionein;absorption;animal tissue;biliary excretion;conference paper;controlled study;feces level;homeostasis;liver level;male;metal binding;mouse;nonhuman;nutritional deficiency;urine level;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];trientine;water","Suzuki, K. T.;Someya, A.;Komada, Y.;Ogra, Y.",2002,15 Jan,http://dx.doi.org/10.1016/S0162-0134%2801%2900376-2,0,0,
2316,Abnormal movements. Diagnostic orientation. [French],,anxiety disorder/di [Diagnosis];anxiety disorder/dt [Drug Therapy];anxiety disorder/th [Therapy];blepharospasm/dt [Drug Therapy];blepharospasm/et [Etiology];chorea/dt [Drug Therapy];chorea/et [Etiology];differential diagnosis;dyskinesia/dt [Drug Therapy];dyskinesia/et [Etiology];dyskinesia/si [Side Effect];dystonia/di [Diagnosis];dystonia/dt [Drug Therapy];dystonia/et [Etiology];essential tremor/dt [Drug Therapy];essential tremor/et [Etiology];genetic counseling;Gilles de la Tourette syndrome/di [Diagnosis];Gilles de la Tourette syndrome/dt [Drug Therapy];Gilles de la Tourette syndrome/et [Etiology];Gilles de la Tourette syndrome/th [Therapy];hemifacial spasm/dt [Drug Therapy];hemifacial spasm/et [Etiology];human;Huntington chorea/di [Diagnosis];Huntington chorea/dt [Drug Therapy];Huntington chorea/et [Etiology];kinesiotherapy;Meige disease/di [Diagnosis];Meige disease/dt [Drug Therapy];Meige disease/et [Etiology];mental disease/di [Diagnosis];mental disease/dt [Drug Therapy];mental disease/th [Therapy];motor dysfunction/di [Diagnosis];motor dysfunction/dt [Drug Therapy];motor dysfunction/et [Etiology];motor dysfunction/si [Side Effect];motor dysfunction/th [Therapy];myoclonus/dt [Drug Therapy];myoclonus/et [Etiology];parkinsonism/dt [Drug Therapy];parkinsonism/et [Etiology];psychotherapy;relaxation training;review;spasmodic torticollis/di [Diagnosis];spasmodic torticollis/dt [Drug Therapy];spasmodic torticollis/et [Etiology];tardive dyskinesia/dt [Drug Therapy];tardive dyskinesia/et [Etiology];tardive dyskinesia/si [Side Effect];tic/dt [Drug Therapy];tic/et [Etiology];tremor/dt [Drug Therapy];tremor/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];benzodiazepine/dt [Drug Therapy];botulinum toxin/ad [Drug Administration];botulinum toxin/do [Drug Dose];botulinum toxin/dt [Drug Therapy];botulinum toxin/im [Intramuscular Drug Administration];cholinergic receptor blocking agent/dt [Drug Therapy];haloperidol/dt [Drug Therapy];levodopa/do [Drug Dose];levodopa/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];olanzapine/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];risperidone/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy],"Vidailhet, M.",2002,01 Dec,,0,0,
2317,Cancer therapy with tetrathiomolybdate: Antiangiogenesis by lowering body copper - A review,"A new anticopper drug, tetrathiomolybdate (TM), developed for Wilson's disease, is a very promising antiangiogenic agent. Copper levels lowered into an antiangiogenic window by TM have shown efficacy against cancer in a variety of animal models as well as in patients. The only significant toxicity so far results from overtreatment and excessive bone marrow depletion of copper. The resulting anemia and/or leukopenia is easily treatable by dose reduction or drug holiday. The underlying concept for TM efficacy as an anticancer agent is that when the body's copper status is in the window, cellular copper needs are met and toxicity is avoided. Copper status is relatively easily monitored by following serum ceruloplasmin, a copper-containing protein secreted by the liver at a rate dependent upon the amount of copper in the liver available to incorporate into the protein. The authors speculate that the copper level is a primitive angiogenesis and growth-signaling regulator that has been retained throughout evolution.",anemia/et [Etiology];animal;autoimmune disease/si [Side Effect];bone marrow suppression/et [Etiology];bone marrow suppression/si [Side Effect];cancer chemotherapy;ceruloplasmin blood level;clinical trial;connective tissue disease/si [Side Effect];copper blood level;drug dose reduction;drug efficacy;human;kidney disease/si [Side Effect];leukopenia/et [Etiology];liver toxicity/si [Side Effect];metabolism;neoplasm/dt [Drug Therapy];nonhuman;priority journal;protein secretion;proteinuria/si [Side Effect];review;side effect/si [Side Effect];stomach disease/si [Side Effect];Wilson disease/dt [Drug Therapy];angiogenesis inhibitor/ae [Adverse Drug Reaction];angiogenesis inhibitor/dt [Drug Therapy];angiogenesis inhibitor/to [Drug Toxicity];angiogenesis inhibitor/pd [Pharmacology];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];molybdenum/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/to [Drug Toxicity];tetrathiomolybdic acid/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/it [Drug Interaction],"Brewer, G. J.;Merajver, S. D.",2002,December,http://dx.doi.org/10.1177/1534735402238185,0,0,
2318,Wilson disease manifested primarily as amenorrhea and accompanying thrombocytopenia,,adolescent;amenorrhea;article;case report;clinical feature;female;hepatitis;human;laboratory test;liver cirrhosis/di [Diagnosis];liver fibrosis;liver necrosis;needle biopsy;physical examination;priority journal;thrombocytopenia;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Erkan, T.;Aktuglu, C.;Gulcan, E. M.;Kutlu, T.;Cullu, F.;Apak, H.;Tumay, G. T.",2002,October,http://dx.doi.org/10.1016/S1054-139X%2802%2900355-5,0,0,
2319,Copper and angiogenesis - A new piece to the puzzle,,angiogenesis;breast cancer/dt [Drug Therapy];cancer inhibition;chemoprophylaxis;clinical trial;controlled clinical trial;controlled study;copper deficiency;drug safety;head and neck cancer/dt [Drug Therapy];high risk patient;human;mesothelioma/dt [Drug Therapy];multiple myeloma/dt [Drug Therapy];nonhuman;note;priority journal;prostate cancer/dt [Drug Therapy];tumor vascularization;Wilson disease/dt [Drug Therapy];antineoplastic agent/cb [Drug Combination];antineoplastic agent/dt [Drug Therapy];copper;immunoglobulin enhancer binding protein/ec [Endogenous Compound];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];vasculotropin/ec [Endogenous Compound],"Habeck, M.",2002,01 Nov,,0,0,
2320,Diseases of the liver: Chronic liver disease,,alcohol liver cirrhosis/di [Diagnosis];alcohol liver cirrhosis/dt [Drug Therapy];alcohol liver cirrhosis/et [Etiology];ascites/dt [Drug Therapy];ascites/et [Etiology];autoimmune disease/di [Diagnosis];autoimmune disease/dt [Drug Therapy];autoimmune disease/et [Etiology];autoimmune disease/su [Surgery];bacterial peritonitis/co [Complication];bacterial peritonitis/dt [Drug Therapy];bone marrow toxicity/si [Side Effect];chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];chronic liver disease/et [Etiology];chronic liver disease/su [Surgery];clinical trial;disease classification;drug induced disease/si [Side Effect];esophagus varices bleeding/co [Complication];esophagus varices bleeding/dt [Drug Therapy];esophagus varices bleeding/th [Therapy];hepatic encephalopathy/co [Complication];hepatic encephalopathy/dt [Drug Therapy];hepatitis B/di [Diagnosis];hepatitis B/dt [Drug Therapy];hepatitis B/et [Etiology];hepatitis C/di [Diagnosis];hepatitis C/dt [Drug Therapy];hepatitis C/et [Etiology];human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/su [Surgery];liver toxicity/si [Side Effect];liver transplantation;lupus erythematosus/si [Side Effect];meta analysis;nephrotoxicity/si [Side Effect];plasmapheresis;primary biliary cirrhosis/di [Diagnosis];primary biliary cirrhosis/dt [Drug Therapy];primary biliary cirrhosis/et [Etiology];primary biliary cirrhosis/su [Surgery];primary sclerosing cholangitis/di [Diagnosis];primary sclerosing cholangitis/dt [Drug Therapy];primary sclerosing cholangitis/et [Etiology];primary sclerosing cholangitis/su [Surgery];pruritus/dt [Drug Therapy];pruritus/et [Etiology];review;virus hepatitis/di [Diagnosis];virus hepatitis/dt [Drug Therapy];virus hepatitis/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];aldosterone antagonist/do [Drug Dose];aldosterone antagonist/dt [Drug Therapy];alpha interferon/ct [Clinical Trial];alpha interferon/cb [Drug Combination];alpha interferon/do [Drug Dose];alpha interferon/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];alpha2b interferon/ct [Clinical Trial];alpha2b interferon/cb [Drug Combination];alpha2b interferon/do [Drug Dose];alpha2b interferon/dt [Drug Therapy];antibiotic agent/ae [Adverse Drug Reaction];antibiotic agent/cb [Drug Combination];antibiotic agent/do [Drug Dose];antibiotic agent/dt [Drug Therapy];antioxidant/dt [Drug Therapy];antivirus agent/cb [Drug Combination];antivirus agent/dt [Drug Therapy];antivirus agent/pd [Pharmacology];chelating agent/do [Drug Dose];chelating agent/dt [Drug Therapy];colchicine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];cyanoacrylate;diuretic agent/do [Drug Dose];diuretic agent/dt [Drug Therapy];interferon/ct [Clinical Trial];interferon/cb [Drug Combination];interferon/do [Drug Dose];interferon/dt [Drug Therapy];lamivudine/dt [Drug Therapy];lamivudine/pd [Pharmacology];naloxone/ad [Drug Administration];naloxone/dt [Drug Therapy];naloxone/sc [Subcutaneous Drug Administration];naltrexone/ad [Drug Administration];naltrexone/dt [Drug Therapy];naltrexone/po [Oral Drug Administration];neomycin/ae [Adverse Drug Reaction];neomycin/dt [Drug Therapy];octreotide/ct [Clinical Trial];octreotide/dt [Drug Therapy];ondansetron/ad [Drug Administration];ondansetron/dt [Drug Therapy];ondansetron/iv [Intravenous Drug Administration];ondansetron/po [Oral Drug Administration];oxandrolone/dt [Drug Therapy];peginterferon alpha2b/ct [Clinical Trial];peginterferon alpha2b/cb [Drug Combination];peginterferon alpha2b/do [Drug Dose];peginterferon alpha2b/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];rifampicin/ae [Adverse Drug Reaction];rifampicin/do [Drug Dose];rifampicin/dt [Drug Therapy];silymarin/dt [Drug Therapy];spironolactone/do [Drug Dose];spironolactone/dt [Drug Therapy];trientine/do [Drug Dose];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy],"Kennedy, P. T. F.;O'Grady, J. G.",2002,,,0,0,
2321,"Interactions between Zn and Cu in LEC rats, an animal model of Wilson's disease","The effect of oral Zn treatment was studied in the liver and kidneys of 26 male Long-Evans Cinnamon (LEC) rats (mutant animals, 5 weeks old) in relation to both the interaction between Zn and Cu and the localisation and concentration of metallothionein (MT). Rats receiving 80 mg zinc acetate daily by gavage and control rats receiving no treatment were killed after 1 or 2 weeks. By immunohistochemical and analytical chemical techniques we revealed that treated rats had higher levels of MT in the hepatic and renal cells compared to untreated ones. Tissue Zn concentrations were significantly higher in treated rats compared to untreated whereas Cu concentrations decreased in the liver and kidneys as indicated by analytical chemical analyses. MT levels also decreased with treatment period. A histochemical procedure, obtained using autofluorescence of Cu-metallothioneins, confirms these findings: after 2 weeks, the signal decreased in both the liver and kidney sections. This gives a greater understanding of the mechanism of Cu metabolism in the two tissues considered. These results suggest that Zn acts both to compete for absorption on the luminal side of the intestinal epithelium and to induce the synthesis of MT.",Autofluorescence;Immunolocalisation;LEC rats;Metallothionein;Metals;animal cell;animal experiment;animal model;animal tissue;article;cell level;concentration (parameters);controlled study;copper metabolism;histochemistry;intestine absorption;intestine epithelium;kidney cell;liver cell;male;mouse;nonhuman;priority journal;protein localization;protein synthesis;signal transduction;tissue level;Wilson disease;copper/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];zinc/ec [Endogenous Compound];zinc acetate/po [Oral Drug Administration];zinc acetate/pd [Pharmacology],"Santon, A.;Giannetto, S.;Sturniolo, G.;Medici, V.;D'Inca, R.;Irato, P.;Albergoni, V.",2002,,http://dx.doi.org/10.1007/s00418-002-0380-8,0,0,
2322,Albumin dialysis and molecular adsorbents recirculating system (MARS) for acute Wilson's disease,"Wilson's disease presenting as acute liver failure (ALF) is potentially fatal, and liver transplantation (LTx) is the only option. We report two patients with Wilson's disease add ALF treated with the Molecular Adsorbents Recirculating System (MARS). Both patients fulfilled criteria for poor prognosis. Because LTx was not available immediately in either case, MARS was used as a bridge to LTx. In Case 1, serum bilirubin decreased from 803 to 425 mumol/L after 3 treatments, but increased to 656 mumol/L during a break, decreasing again to 457 mumol/L with further treatment. Serum copper decreased from 53.7 mumol/L, to 35.8 mumol/L after first treatment session, and 17.4 mumol/L at treatment completion. In Case 2, MARS treatment over 2 weeks reduced serum bilirubin from 1200 to 450 mumol/L and copper from 35 to 13 mumol/L with marked improvement in encephalopathy and reduction in ammonia (59 to 34 mumol/L). Both patients were successfully bridged to LTx (days 9 and 28, respectively). Analysis of albumin-dialysate from the MARS circuit suggested that copper removal occurred mostly in the first few hours of treatment, partly being adsorbed by albumin and partly by the MARSFlux membrane (Teraklin AG, Rostock, Germany). These data suggest that MARS removes copper efficiently and can be used to bridge patients with Wilson's disease and ALF LTx.",adsorption;adult;albumin dialysis;ammonia blood level;article;artificial liver;bilirubin blood level;case report;copper blood level;dialysate;dialysis membrane;equipment design;female;hemodialysis;hepatic encephalopathy/co [Complication];hepatic encephalopathy/th [Therapy];human;liver failure/su [Surgery];liver failure/th [Therapy];liver transplantation;priority journal;prognosis;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];ak100;albumin;ammonia/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];BSM 22c;copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];progesterone/im [Intramuscular Drug Administration];unclassified drug,"Sen, S.;Felldin, M.;Steiner, C.;Larsson, B.;Gillett, G. T.;Olausson, M.;Williams, R.;Jalan, R.",2002,01 Oct,http://dx.doi.org/10.1053/jlts.2002.35546,0,0,
2323,Chronic liver disease in two children exposed to moderately high levels of copper in drinking water,"Two unrelated children came to our observation for a persistent, isolated, and clinically asymptomatic cryptogenic hypertransaminasemia. Liver histology was unspecific. Urine Cu excretion after penicillamine and hepatic Cu were high but not within the usual Wilson disease (WD) range. Molecular analysis of WD gene was normal. Tap water at home contained Cu concentrations >= 0.3 mg/l. After lowering Cu intake, urine Cu excretion following penicillamine decreased and transaminase values normalized in both. We suggest that moderately high levels of Cu in drinking water may cause a reversible and mild liver disease, different from other severe forms of copper-related cirrhosis.",Copper Toxicosis;Liver disease;Water;aminotransferase blood level;article;case report;ceruloplasmin blood level;chemical analysis;chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];chronic liver disease/et [Etiology];clinical feature;controlled study;copper blood level;copper toxicity/di [Diagnosis];copper toxicity/dt [Drug Therapy];copper toxicity/et [Etiology];differential diagnosis;disease course;environmental exposure;exon;gene;gene sequence;hepatitis/di [Diagnosis];histopathology;home;human;hypertransaminasemia/di [Diagnosis];hypertransaminasemia/dt [Drug Therapy];hypertransaminasemia/et [Etiology];Italy;liver cirrhosis;liver function test;liver histology;liver toxicity/di [Diagnosis];liver toxicity/dt [Drug Therapy];liver toxicity/et [Etiology];male;nodular hyperplasia/di [Diagnosis];school child;single strand conformation polymorphism;symptom;treatment outcome;urinary excretion;Wilson disease;wilson disease gene;aminotransferase/ec [Endogenous Compound];copper;drinking water;liver enzyme/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Spaziano, M.;Di Maria, F.;Mellone, M.;Loudianos, J.;Ciccimarra, E.;Mandato, C.;Migliaro, F.;Vajro, P.",2002,February,,0,0,
2324,Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc,"The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy- 2'-deoxyguanosine (oh<sup>8</sup>dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.",Antioxidant enzymes;Copper;Long-Evans Cinnamon rat;Metallothionein;Zinc;animal experiment;animal model;animal tissue;article;association;binding site;competition;concentration (parameters);controlled study;enzyme active site;enzyme activity;enzyme analysis;experiment;iron transport;male;nonhuman;oxidation;oxidation reduction reaction;priority journal;rat;rat strain;serosa;synthesis;tissue level;8 hydroxydeoxyguanosine;antioxidant/ec [Endogenous Compound];enzyme/ec [Endogenous Compound];free radical/ec [Endogenous Compound];iron;metal;metallothionein/ec [Endogenous Compound];protein;superoxide dismutase/ec [Endogenous Compound];zinc/ec [Endogenous Compound];zinc acetate,"Medici, V.;Santon, A.;Sturniolo, G.;D'Inca, R.;Giannetto, S.;Albergoni, V.;Irato, P.",2002,,http://dx.doi.org/10.1007/s00204-002-0377-z,0,0,
2325,Diagnosing Wilson's disease in a 5-year-old child,,aminotransferase blood level;analytical parameters;article;case report;childhood;clinical feature;differential diagnosis;enzyme blood level;follow up;gas chromatography;hematological parameters;human;human tissue;liver biopsy;liver function;liver level;male;physical examination;preschool child;priority journal;rehydration;serology;virus hepatitis/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];copper/ec [Endogenous Compound];liver enzyme/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy],"Hui, J.;Fung, E. L. W.;Tang, N. L. S.;Chan, M. H. M.;To, K. F.;Fok, T. F.",2002,,http://dx.doi.org/10.1046/j.1440-1754.2002.00023.x,0,0,
2326,Autonomic dysfunction in Wilson's disease - A clinical and electrophysiological study,"Wilson's disease is known for its protean manifestations; however involvement of the autonomic nervous system has not received much attention. Fifty patients with varying duration and severity of illness were evaluated for autonomic dysfunction clinically and electrophysiologically, using sympathetic skin response (SSR) and RR interval variability (RRIV) on deep breathing. The change in heart rate (DELTAHR) was calculated from RRIV. Five patients had at least one autonomic symptom and one asymptomatic patient had significant postural hypotension. Absent SSR and abnormal DELTAHR were noted in seven patients each. Overall, 13 patients had electrophysiological dysautonomia and an additional six had clinical dysautonomia. All had normal peripheral conductions and all but one had normal hepatic functions. Dysautonomia was more common among patients with neurological presentation (12/32) than non-neurological (1/18) (p = .012). Dysautonomia, often subclinical is common in Wilson's disease and is probably of central origin. It is more frequent among those with neurological presentation. Sympathetic and parasympathetic functions are equally affected.",Dysautonomia;R-R interval variability;Sympathetic skin response;Wilson's disease;adolescent;adult;article;autonomic dysfunction;autonomic nervous system;calculation;child;cholinergic system;clinical article;clinical feature;controlled study;disease duration;disease severity;electrophysiology;female;human;hyperpnea;liver function;male;nerve conduction;orthostatic hypotension;RR interval;sympathetic function;sympathetic tone;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Meenakshi-Sundaram, S.;Taly, A. B.;Kamath, V.;Arunodaya, G. R.;Rao, S.;Swamy, H. S.",2002,,,0,0,
2327,"Ceruloplasmine and iron metabolism: The implications in hemochromatosis, Wilson's disease and aceruloplasminemia. [Spanish]",,aceruloplasminemia/di [Diagnosis];aceruloplasminemia/et [Etiology];adult;article;cell membrane;chromosome 13;chromosome 3;dementia;diagnostic accuracy;dysarthria;dystonia;ferritin blood level;gene mutation;hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];hemoglobin synthesis;human;iron metabolism;iron transport;metabolic disorder/di [Diagnosis];metabolic disorder/et [Etiology];neurologic disease;pathophysiology;protein metabolism;protein synthesis;retina degeneration;symptomatology;trans Golgi network;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];aminotransferase/ec [Endogenous Compound];apoprotein/ec [Endogenous Compound];ascorbic acid;ceruloplasmin/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine,"Perez-Aguilar, F.",2002,01 Dec,,0,0,
2328,Case reports: D-penicillamine induced myasthenia gravis,"Myasthenia gravis is a disorder of impaired neuromuscular transmission resulting in weakness and abnormal fatigability on exertion, improved by anti-acetyl cholinesterase drugs. A number of drugs are known to exacerbate myasthenia gravis or interfere with neuromuscular transmission. We report a case of D-penicillamine induced myasthenia gravis who developed ptosis, diplopia and easy fatigability, 4 years after initiation of the drug for Wilson's disease. On stopping the drug, within 3 months all her symptoms disappeared without any anti-acetyl cholinesterase drugs. Thus, the onset of drug induced myasthenia gravis could be insidious but the withdrawal of the drug leads to rapid recovery.",article;case report;clinical feature;diplopia/si [Side Effect];disease course;disease exacerbation/di [Diagnosis];disease exacerbation/si [Side Effect];drug withdrawal;fatigue/si [Side Effect];female;follow up;human;myasthenia gravis/di [Diagnosis];myasthenia gravis/si [Side Effect];neuromuscular transmission;ptosis/si [Side Effect];school child;treatment outcome;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Varghese, T.;Ahmed, R.;Sankaran, J. D.;Al-Khusaiby, S. M.",2002,October,,0,0,
2329,Wilson's disease revealed by skin signs. [French],"Wilson's disease or hepato-lenticular degeneration is a rare disease which is rarely associated to skin abnormalities. Exceptionally, skin disorders lead to the diagnosis as in the case reported here. A 17-year-old young man consulted for a lower lip pyogenic granuloma. Complete physical examination showed multiple eruptive spider angiomas of the limbs as clinical signs suggestive of hepatic cirrhosis. The hepatic copper dosage allowed to confirm Wilsonian cirrhosis diagnosis. A treatment with D-penicillamine was quickly started. We describe herein the first case of Wilsonian cirrhosis revelated by vascular proliferations of the skin (pyogenic granuloma and spider angiomas). In our case, Wilsonian cutaneous specific signs were not present (hyperpigmentation on the anterior aspect of the lower part of the legs and azure lunulae).",Cutaneous spider angiomas;Pyogenic granuloma;Wilson's disease;adolescent;article;case report;clinical feature;echography;human;laboratory test;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver function test;male;skin manifestation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Diris, N.;Derancourt, C.;Levy, S.;Bernardeau, K.;Durand, F.;Bernard, P.",2002,,,0,0,
2330,Image of the month,,adult;article;case report;computer assisted tomography;echography;fatty liver/di [Diagnosis];fatty liver/dt [Drug Therapy];human;hyperuricosuria/di [Diagnosis];hyperuricosuria/dt [Drug Therapy];liver biopsy;male;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];glycogen/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];uric acid/ec [Endogenous Compound],"Warshauer, D. M.;Pascual, S.;Such, J.;Quilez, C.",2002,,,0,0,
2331,HFE gene mutations and iron metabolism in Wilson's disease,"Background: There is increasing evidence for an interaction between iron and copper metabolism. Methods: Iron indices (ferritin, transferrin saturation [TS], serum iron), liver parameters, the prevalence and significance of C282Y and H63D HFE mutations were studied in 40 unrelated, Caucasian patients with Wilson's disease and 295 healthy controls. Due to specific treatment Wilson's disease was well controlled in all but one patient. Results: The allele frequencies for the C282Y (11.3% vs. 6.2%) and the H63D (18.8% vs. 16.4%) mutation did not differ between patients with Wilson's disease and healthy controls. One patient with C282Y homozygous HH and Wilson's disease was identified showing progressive liver disease despite reasonable venesection and copper chelation therapy. No differences in iron indices and liver values were seen between HFE heterozygous and HFE wildtype patients with Wilson's disease. Higher serum ferritin levels were noticed in patients with Wilson's disease compared to healthy controls (149 +/- 26 mug/1 vs. 87 +/- 8 mug/1; P < 0.03). Conclusions: It appears reasonable to assess iron indices in patients with Wilson's disease in order to detect iron overload. HFE mutations other than C282Y homozygosity seem to have no impact on iron indices and liver parameters as long as Wilson's disease is controlled.",Copper;Haemochromatosis-mutations;HFE-gene;Iron;Wilson's disease;adolescent;adult;aged;allele;article;Caucasian;chelation therapy;child;clinical article;controlled study;female;ferritin blood level;gene frequency;gene mutation;hepatobiliary parameters;heterozygosity;homozygosity;human;iron blood level;iron metabolism;iron overload/di [Diagnosis];iron overload/th [Therapy];male;phlebotomy;prevalence;wild type;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];ferritin/ec [Endogenous Compound];HFE protein/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Erhardt, A.;Hoffmann, A.;Hefter, H.;Haussinger, D.",2002,December,http://dx.doi.org/10.1034/j.1600-0676.2002.01732.x,0,0,
2332,The liver and pregnancy,"Any liver disorder can occur in women who are pregnant, and pregnancy-related diseases frequently involve the liver, sometimes with disastrous results. Here, the causes, diagnosis and management of liver disorder in pregnancy are reviewed. Treatment is complicated as fetal in addition to maternal well-being has to be considered.",Acute;Liver;Liver function tests;Obstetric;Pre-eclampsia;Pregnancy;alcohol consumption;autoimmune disease/di [Diagnosis];autoimmune disease/dt [Drug Therapy];Budd Chiari syndrome/dt [Drug Therapy];cholecystectomy;cholelithiasis/co [Complication];cholelithiasis/dt [Drug Therapy];cholelithiasis/su [Surgery];chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];drug effect;drug overdose;excretion;fatty liver/co [Complication];fatty liver/di [Diagnosis];female;fetal alcohol syndrome/co [Complication];fetus disease/si [Side Effect];fetus risk;gastrointestinal endoscopy;health care management;HELLP syndrome/dt [Drug Therapy];Hepatitis A virus;hepatitis B/co [Complication];hepatitis B/di [Diagnosis];hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];Hepatitis B virus;hepatitis C/co [Complication];hepatitis C/di [Diagnosis];hepatitis C/dt [Drug Therapy];Hepatitis C virus;Hepatitis E virus;Hepatitis G virus;hospital admission;human;hyperemesis gravidarum/dt [Drug Therapy];hyperemesis gravidarum/th [Therapy];liver cirrhosis/di [Diagnosis];liver disease/co [Complication];liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/ep [Epidemiology];liver disease/su [Surgery];liver function;liver function test;liver injury;liver metabolism;liver rupture/co [Complication];liver rupture/th [Therapy];liver toxicity;mortality;mother;preeclampsia;pregnancy complication/di [Diagnosis];protein synthesis;pruritus/dt [Drug Therapy];review;side effect/si [Side Effect];steatorrhea/si [Side Effect];virus hepatitis;wellbeing;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];acetylsalicylic acid/do [Drug Dose];acetylsalicylic acid/to [Drug Toxicity];aciclovir/dt [Drug Therapy];alcohol/to [Drug Toxicity];amiodarone/do [Drug Dose];amiodarone/to [Drug Toxicity];antibiotic agent/dt [Drug Therapy];anticoagulant agent/dt [Drug Therapy];antiemetic agent/dt [Drug Therapy];antihistaminic agent/dt [Drug Therapy];antihypertensive agent/do [Drug Dose];antihypertensive agent/to [Drug Toxicity];antivirus agent/ae [Adverse Drug Reaction];antivirus agent/cb [Drug Combination];antivirus agent/dt [Drug Therapy];azathioprine/ae [Adverse Drug Reaction];azathioprine/dt [Drug Therapy];colestyramine/ae [Adverse Drug Reaction];colestyramine/dt [Drug Therapy];colestyramine/pd [Pharmacology];dexamethasone/dt [Drug Therapy];fibrinolytic agent/dt [Drug Therapy];hepatitis B antibody/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];interferon/ae [Adverse Drug Reaction];interferon/cb [Drug Combination];interferon/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];methyldopa/do [Drug Dose];methyldopa/to [Drug Toxicity];nonsteroid antiinflammatory agent/do [Drug Dose];nonsteroid antiinflammatory agent/to [Drug Toxicity];paracetamol/do [Drug Dose];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy];phenothiazine derivative/do [Drug Dose];phenothiazine derivative/to [Drug Toxicity];sclerosing agent/ae [Adverse Drug Reaction];sclerosing agent/dt [Drug Therapy];steroid/ae [Adverse Drug Reaction];steroid/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/ae [Adverse Drug Reaction];ursodeoxycholic acid/dt [Drug Therapy];ursodeoxycholic acid/pd [Pharmacology];valproic acid/do [Drug Dose];valproic acid/to [Drug Toxicity];vitamin/dt [Drug Therapy];vitamin B complex/dt [Drug Therapy],"Sillender, M.",2002,December,,0,0,
2333,Zinc in liver disease,"The essentiality of zinc for humans was first documented by Prasad in the 1960s. During the past 35 years, zinc deficiency in humans a result of nutritional factors and several disease states has been recognized. Many of the clinical features of liver cirrhosis have been linked to zinc deficiency, including loss of body hair, testicular atrophy, poor appetite, immune dysfunction, altered taste and smell, reduced vitamin A and thyroid hormone metabolism, altered protein metabolism, delayed wound healing, and diminished drug elimination capacity. One of the most interesting and novel aspects concerning the presumable role of zinc deficiency in producing clinical features of liver cirrhosis is the possible relationship between zinc and hepatic encephalopathy (HE). Long-term zinc supplementation in patients with HE improves neurological symptoms and metabolic parameters. In Wilson's disease, an inherited defect of hepatic copper, zinc is used for maintenance as well as treating presymptomatic, pregnant, and pediatric patients. Zinc may be involved in the pathogenesis of chronic hepatitis C. This work is an attempt to review the information available in this field to understand the important role that zinc plays in the pathogenesis and therapy of several liver diseases. © 2002 Wiley-Liss, Inc.",Chronic liver disease;Zinc deficiency;Zinc supplementation;antioxidant activity;clinical feature;clinical trial;drug effect;drug efficacy;drug mechanism;hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/et [Etiology];hepatitis C/dt [Drug Therapy];hepatitis C/et [Etiology];human;hyperammonemia/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver protection;membrane stabilization;priority journal;review;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];zinc deficiency/di [Diagnosis];zinc deficiency/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];ammonia/to [Drug Toxicity];copper/to [Drug Toxicity];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/ct [Clinical Trial];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc/pd [Pharmacology],"Grngreiff, K.",2002,,http://dx.doi.org/10.1002/jtra.10002,0,0,
2334,Wilson's disease,"Sir Alexander Kinnear Wilson made the original description of a syndrome of hepatolenticular degeneration almost a century ago, correctly postulating a connection between the observed cirrhosis of the liver and the neurologic signs and symptoms. However, copper was not known then to be the etiopathologic agent. Although the genetic basis of this disease is now clear, our understanding of its pathogenesis is still evolving. Wilson's disease (WD), as the syndrome was later named, is an autosomal recessive disorder that results from mutations of the adenosine triphosphatase 7B (ATP7B) gene on chromosome 13. This gene encodes a copper transporter in hepatocytes critical for the hepatic excretion of excess copper into bile. WD, although a relatively uncommon inherited disorder of copper metabolism present in approximately 1 of 30,000 individuals, is commonly considered in the differential diagnosis of patients less than age 45 years with fulminant hepatic failure or unexplained liver disease or in patients with neurologic or psychiatric symptoms and liver disease. When WD is identified and treated appropriately, disease progression is prevented, and reversal of copper-induced injury may occur. Specific clinical and biochemical findings used to establish the diagnosis include serum ceruloplasmin, serum and urine copper, corneal Kayser-Fleischer rings and hepatic histology, histochemistry, and copper content. Identification of the gene has enabled testing with haplotype analysis for siblings of identified patients and direct mutation analysis for de novo diagnosis within specific populations with dominant mutations. Treatment is lifelong medical therapy with chelating agents or zinc to remove copper or prevent its absorption or liver transplantation, which cures the metabolic defect.",chromosome 13;clinical feature;copper metabolism;diagnostic test;differential diagnosis;disease course;gene identification;gene mutation;haplotype;histochemistry;human;liver biopsy;liver disease/di [Diagnosis];liver failure/di [Diagnosis];liver failure/su [Surgery];liver histology;liver transplantation;nuclear magnetic resonance imaging;pathophysiology;patient monitoring;prognosis;review;side effect/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/cb [Drug Combination];chelating agent/cm [Drug Comparison];chelating agent/dt [Drug Therapy];chelating agent/po [Oral Drug Administration];copper;dimercaprol/cb [Drug Combination];dimercaprol/dt [Drug Therapy];dimercaprol/pa [Parenteral Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/po [Oral Drug Administration];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Schilsky, M. L.",2002,,,0,0,
2335,"Acute, progressive akinetic-rigid syndrome induced by neuroleptics in a case of wilson's disease [4]",,adult;akinesia/si [Side Effect];case report;clinical feature;disability;extrapyramidal symptom/si [Side Effect];human;letter;male;muscle rigidity/si [Side Effect];paranoia/co [Complication];paranoia/dt [Drug Therapy];priority journal;psychosis/co [Complication];psychosis/dt [Drug Therapy];scoring system;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];benserazide plus levodopa/do [Drug Dose];benserazide plus levodopa/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];olanzapine/ae [Adverse Drug Reaction];olanzapine/do [Drug Dose];olanzapine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];risperidone/ae [Adverse Drug Reaction];risperidone/do [Drug Dose];risperidone/dt [Drug Therapy];ropinirole/do [Drug Dose];ropinirole/dt [Drug Therapy],"Chroni, E.;Lekka, N. P.;Tsibri, E.;Economou, A.;Paschalis, C.",2001,,http://dx.doi.org/10.1176/appi.neuropsych.13.4.531,0,0,
2336,Wilson's disease: A case and review of the litterature. [French],"Wilson's disease: a case and review of the litterature. Wilson disease is a relatively rare autosomal recessive inherited disorder of copper transport resulting from toxic copper accumulation in liver and brain. In patients with Wilson's disease, both copper incorporation into ceruloplasmin and excretion of this metal into bile are impaired. These conditions are caused by a genetic defect in the Wilson's disease gene (ATP7B), which maps to chromosome 13. The diagnosis is based on clinical findings, results of key laboratory tests such as low serum ceruloplasmin level, increased urinary copper excretion, and hepatic copper content and presence of Kayser-Fleischer rings. An emerging method to diagnosis is the use of molecular techniques. Several treatments are available to increase urinary excretion and decrease intestinal absorption of copper. We report a case of neurological Wilson's disease. Family survey found three siblings reached, without symptoms, who therefore hed preventive treatment. © 2001 editions scientifiques et medicales Elsevier SAS.",ceruleoplasmine;ceruleoplasmin;copper;cuivre;genetique;genetics;maladie de Wilson;Wilson disease;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];bile flow;chromosome 13;chromosome map;copper metabolism;eye disease;genetic disorder;hemolytic anemia;human;intestine absorption;liver disease;mental disease;molecular mechanics;musculoskeletal disease;neuroimaging;neurologic disease;pathophysiology;priority journal;protein blood level;review;toxicity;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Ardelean-Jaby, D.;De Broucker, T.;Cailliez, M.",2001,November/December,http://dx.doi.org/10.1016/S0923-2532%2801%2980072-7,0,0,
2337,Wilson disease,,adult;article;case report;ceruloplasmin blood level;clinical feature;cornea opacity;gonioscopy;human;male;physical examination;priority journal;saccadic eye movement;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Patel, A. D.;Bozdech, M.",2001,,,0,0,
2338,The irony of treating Wilson's disease,,case report;dose response;editorial;human;iron blood level;iron overload/si [Side Effect];liver biopsy;male;pathophysiology;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/cb [Drug Combination];zinc/do [Drug Dose];zinc/dt [Drug Therapy],"Schilsky, M. L.",2001,,http://dx.doi.org/10.1016/S0002-9270%2801%2903816-3,0,0,
2339,Diagnosis and management of chronic liver disease,"* The most common causes of chronic liver disease are fatty liver, alcohol, viral hepatitis and drug toxicity. * A routine initial approach to investigation helps both diagnosis and treatment decisions. * General management includes dietary and vaccination considerations. * Specific treatment varies with the primary disorder and can significantly improve prognosis. * Sudden weight loss in patients with fatty liver can precipitate worsening LFTs. * Evidence of decompensation is associated with decreased survival. * Liver transplantation provides good outcomes in selected patients.",alcohol abstinence;alcohol consumption;alpha 1 antitrypsin deficiency/th [Therapy];article;autoimmune hepatitis/dt [Drug Therapy];biliary cirrhosis/dt [Drug Therapy];biliary cirrhosis/su [Surgery];blood cell count;cholangiography;chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];chronic liver disease/et [Etiology];chronic liver disease/pc [Prevention];chronic liver disease/si [Side Effect];chronic liver disease/su [Surgery];chronic liver disease/th [Therapy];clinical feature;computer assisted tomography;diet therapy;disease association;drug induced disease/si [Side Effect];echography;endoscopic therapy;erythema;fatty liver;gynecomastia;hemochromatosis/di [Diagnosis];hemochromatosis/su [Surgery];hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];Hepatitis B virus;hepatitis C/dt [Drug Therapy];Hepatitis C virus;Hepatitis delta virus;hepatosplenomegaly;human;liver biopsy;liver function test;liver transplantation;medical assessment;muscle atrophy;nail disease;phlebotomy;pigmentation;primary sclerosing cholangitis/di [Diagnosis];primary sclerosing cholangitis/su [Surgery];prognosis;serology;smoking cessation;survival;testis atrophy;treatment outcome;virus hepatitis/dt [Drug Therapy];virus hepatitis/et [Etiology];virus hepatitis/pc [Prevention];weight reduction;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];alpha 1 antitrypsin/ec [Endogenous Compound];amoxicillin plus clavulanic acid/ae [Adverse Drug Reaction];antinuclear antibody/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];azahexal;azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];d penamine;famciclovir/dt [Drug Therapy];ferritin/ec [Endogenous Compound];flucloxacillin/ae [Adverse Drug Reaction];gamma glutamyltransferase/ec [Endogenous Compound];h b vax ii;havrix 1400;hepatitis A hepatitis B vaccine/dt [Drug Therapy];hepatitis A hepatitis B vaccine/pd [Pharmacology];hepatitis A vaccine/dt [Drug Therapy];hepatitis A vaccine/pd [Pharmacology];hepatitis B vaccine/dt [Drug Therapy];hepatitis B vaccine/pd [Pharmacology];hydroxymethylglutaryl coenzyme A reductase inhibitor/ae [Adverse Drug Reaction];immunoglobulin/ec [Endogenous Compound];lamivudine/dt [Drug Therapy];lamivudine/po [Oral Drug Administration];mitochondrion antibody/ec [Endogenous Compound];nonsteroid antiinflammatory agent/ae [Adverse Drug Reaction];panafcort;penicillamine/dt [Drug Therapy];prednisolone;prednisone/cb [Drug Combination];prednisone/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];rebetron/dt [Drug Therapy];thioprine;transferrin/ec [Endogenous Compound];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];zinc derivative/dt [Drug Therapy];zinc derivative/po [Oral Drug Administration],"Feller, R.;McCaughan, G.",2001,,,0,0,
2340,Molecular diagnosis of Wilson disease,"Wilson disease (WD) is caused by mutations in the ATP7B gene. The diagnosis is based on clinical and biochemical criteria but these are increasingly recognized to have low sensitivity. Genetic diagnosis is considered impractical due to the large coding region of the ATP7B gene and extreme diversity of mutations. We assessed the feasibility and utility of genetic diagnosis in WD. The coding region of the ATP7B gene was scanned by single-stranded conformation polymorphism (SSCP) analysis in 6 cases in whom the diagnosis of WD was uncertain. In addition, we attempted molecular diagnosis in 26 WD patients of similar ethnicity but variable disease manifestations. In 6 individuals in whom the biochemical/clinical diagnosis was uncertain, DNA analyses were useful for assigning their status with respect to WD. Molecular diagnosis identified presymptomatic individuals in families affected by WD and assigned heterozygote carrier or wild-type status to individuals previously diagnosed as affected. In 26 WD patients, 92% of disease alleles were identified. The most common mutations were H1069Q, L936X, and 2532delA representing 48, 10, and 8% of disease alleles, respectively. Three novel mutations were identified: Q898R, 3061(-1)g -> a, and 3972insC. Genetic diagnosis is feasible for WD. Greater application of molecular diagnosis should enable an appreciation of the full spectrum of WD phenotype that is not possible with currently available diagnostic criteria. © 2001 Academic Press.",atp7b;Diagnosis;Genotype;Heterozygote;Mutation;Phenotype;Wilson;adult;allele;article;child;clinical article;diagnostic test;DNA determination;ethnology;female;gene mutation;genetic analysis;heterozygosity;human;male;pedigree;polymerase chain reaction;priority journal;promoter region;single strand conformation polymorphism;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Butler, P.;McIntyre, N.;Mistry, P. K.",2001,,http://dx.doi.org/10.1006/mgme.2000.3143,0,0,
2341,Wilson's disease. [French],,adult;article;case report;clinical feature;disease course;female;human;nuclear magnetic resonance imaging;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Martin-Duverneuil, N.;De Broucker, T.",2001,,,0,0,
2342,Dystonia in Wilson's disease,"The frequency and type of dystonic movements, as well as brain abnormalities, as depicted with magnetic resonance imaging (MRI), which might correlate with dystonia, were studied in 27 consecutive patients with a neurologic form of Wilson's disease (WD) and optimized treatment. Dystonia was found in 10 patients (37%), being generalized in half of them, while two patients had segmental, two patients multifocal dystonia, and one patient bilateral foot dystonia. Dystonia was a presenting sign in four patients and developed later in the course of the disease in six patients, despite the administered therapy for WD. Putamen was the only structure significantly more frequently lesioned in dystonic (80%) in comparison to WD patients without dystonia (24%), suggesting a relation between abnormalities in this brain region and dystonic movements in WD. © 2001 Movement Disorder Society.",Dystonia;mri;Putamen;Wilson's disease;adolescent;adult;article;brain injury;brain malformation/di [Diagnosis];brain region;clinical article;clinical feature;controlled study;disease course;female;human;male;nuclear magnetic resonance imaging;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration],"Svetel, M.;Kozic, D.;Stefanova, E.;Semnic, R.;Dragasevic, N.;Kostic, V. S.",2001,July,http://dx.doi.org/10.1002/mds.1118,0,0,
2343,A case of penicillamine dermatopathy. [Korean],Penicillamine dermatopathy refers to the characteristic hemorrhagic skin lesions found in persons receiving long-term penicillamine therapy for either Wilson's disease or cystinuria. These lesions are thought to develop as a result of faulty collagen and elastin synthesis. We described a 31-year-old woman with Wilson's disease who developed mild pruritic grouped matchhead-sized cream-colored papules on the dark reddish plaques on both knees and elbows.,Penicillamine dermatopathy;Wilson's disease;adult;antibiotic therapy;article;case report;collagen synthesis;cystinuria/dt [Drug Therapy];female;human;long term care;papular skin disease/si [Side Effect];skin disease/si [Side Effect];Wilson disease/dt [Drug Therapy];elastin/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Pyo, J. Y.;Lee, W. J.;Koo, D. W.",2001,,,0,0,
2344,Clozapine for psychiatric disorders in a patient with Wilson's disease [1]. [French],,adult;case report;drug efficacy;human;letter;male;mental disease/dt [Drug Therapy];neurologic examination;Parkinson disease/dt [Drug Therapy];Wilson disease/di [Diagnosis];clozapine/dt [Drug Therapy];penicillamine;propranolol;zinc sulfate,"Krim, E.;Barroso, B.",2001,21 Apr,,0,0,
2345,Reversal of neurologic symptoms in Wilson's disease - Case report and review of the literature. [German],"On admission, a 19-year-old patient presented progressive psychomotoric deterioration. One year before ""idiopathic"" hepatic cirrhosis with acute decompensation had been seen. Now, Wilson's disease was diagnosed and standard therapy was started with D-Penicillamin. Nevertheless the disease progressed revealing neurologic symptoms such os dysorthrophonio, brodykinesio, tremor and dystania. Despite of changing the medication these symptoms could not be controlled. Two years later orthotopic liver transplantation become necessary leading to gradual improvement of the neurologic symptoms except of dysartrophania. Besides, the improvement correlated with the changes in magnetic resonance imaging. In the basal ganglia the typical symmetrical hypaintensities were regredient. We conclude that therapy resistant neurologic symptoms in patients with Wilson's disease may improve if treated with orthotopic liver transplantation even if these exist far a long time.",Hepato-lenticular degeneration;Liver transplantation;Morbus Wilson;adult;article;basal ganglion;bradykinesia;case report;deterioration;disease association;disease course;dystonia;human;liver cirrhosis/su [Surgery];neurologic disease;nuclear magnetic resonance imaging;treatment outcome;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Eggers, B.;Hermann, W.;Dannenberg, C.;Kuhn, H. J.;Grahmann, F.;Schenker, E.;Wagner, A.",2001,,,0,0,
2346,Excitatory and inhibitory mechanisms in Wilson's disease: Investigation with magnetic motor cortex stimulation,"We have evaluated cortical excitability in nine patients affected by Wilson's disease (WD) using transcranial magnetic (TMS) and electric (TES) cortical stimulation and central silent period (CSP) data. A clinical score was derived from the sum of scores assigned to extrapyramidal, pyramidal and cerebellar signs. All patients underwent TMS. Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles were recorded. MEP threshold and amplitude, central motor conduction time (CMCT), CSP threshold, CSP and peripheral silent period (PSP) duration were measured. Three patients also underwent transcranial bifocal electric cortical stimulation (TES) and MEPs were recorded from the APB muscle, and CMCT, MEP threshold and amplitude were measured. TMS MEPs were absent from relaxed muscles in six patients and from contracted muscles in three. CMCT was prolonged in six patients. APB CMCT correlated with clinical score. In three patients in whom TMS revealed abnormal or no MEP, TES MEPs were of normal threshold and amplitude. The CSP threshold was increased in seven patients, and CSP was absent in one. These results suggest an intracortical presynaptic motor dysfunction in WD. Copyright © 2001 Elsevier Science B.V.",Transcranial magnetic electric cortical stimulation;Wilson's disease;abductor pollicis brevis muscle;adult;article;cerebellum;clinical article;clinical feature;electrostimulation;evoked muscle response;extrapyramidal symptom;extrapyramidal system;female;human;male;motor cortex;motor dysfunction/di [Diagnosis];motor dysfunction/et [Etiology];motor nerve conduction;motor performance;nerve cell excitability;nerve cell inhibition;nuclear magnetic resonance imaging;presynaptic nerve;priority journal;pyramidal tract;scoring system;skeletal muscle;thumb;tibialis anterior muscle;transcranial magnetic stimulation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Perretti, A.;Pellecchia, M. T.;Lanzillo, B.;Campanella, G.;Santoro, L.",2001,15 Nov,http://dx.doi.org/10.1016/S0022-510X%2801%2900594-9,0,0,
2347,Wilson disease,,ceruloplasmin blood level;chronic hepatitis/co [Complication];clinical feature;conference paper;copper metabolism;diagnostic test;human;liver biopsy;liver transplantation;mental disease/co [Complication];neurologic disease/co [Complication];pathogenesis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Ferenci, P.",2001,,,0,0,
2348,"Wilson's disease and ""old skin"". [French]",,aged;article;autoimmune disease/si [Side Effect];autosomal inheritance;blood toxicity/si [Side Effect];case report;clinical feature;elasticity;gastrointestinal toxicity/si [Side Effect];human;human tissue;nephrotoxicity/si [Side Effect];skin biopsy;skin defect/si [Side Effect];stereotaxis;thorax radiography;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Fraysse, T.;De Wazieres, B.",2001,,,0,0,
2349,Acute hemolytic anemia as the first manifestation of wilson's disease: Report of two cases. [French],"Introduction. - The liver and central nervous system are the usual targets of Wilson's disease, an inherited disorder of copper metabolism. Severe hemolytic anemia is an unusual complication of Wilson's disease. Exegesis. - We report two cases of Wilson's disease revealed by acute intravascular hemolytic anemia associated with fiver failure. Blood smear analysis showed stippled red cells in one case; hemolytic anemia improved within a few weeks in both patients but progressive fiver failure required transplantation in the other. Hemolysis probably results from the toxic effect of free serum copper on erythrocyte membrane. Conclusion. - Diagnosis of Wilson's disease must be considered in case of acute hemolytic anemia associated with fiver failure in young adults. © 2001 Editions scientifiques et medicales Elsevier SAS.",Haemolytic anemia;Stippled red cells;Wilson's disease;adolescent;adult;article;blood smear;case report;copper blood level;disease association;erythrocyte;hemolytic anemia/et [Etiology];human;liver failure/su [Surgery];liver transplantation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Michel, M.;Lafaurie, M.;Noel, V.;Pico, L.;Bastie, A.;Godeau, B.;Schaeffer, A.",2001,,http://dx.doi.org/10.1016/S0248-8663%2800%2900329-5,0,0,
2350,Acute worsening of symptoms in a patient with Wilson's Disease following therapy with penicillamine. [German],"Wilson s Disease (WD) is an autosomal recessive disorder leading to abnormal copper accumulation in liver, CNS, cornea and other organs. It is characterized by neurological symptoms, psychiatric abnormalities, hepatic disorders and a variety of other symptoms. Patients should be treated in an early stage of the disease to reduce the pathologic copper accumulation and to prevent chronic damage of the organs. A very fast ""decoppering"" with penicillamine, however, can lead to a worsening of the symptoms which then needs an adaption of the therapy. We present the case of a patient with WD who experienced a marked worsening of neurologic and psychiatric findings after initiation of treatment with penicillamine. The therapy had to be changed after one month. Referring to this case report we review the relevant literature concerning the clinical picture of WD and the problem of intolerance to penicillamine.",Copper accumulation;Penicillamine therapy;Side effects;Wilson's Disease;adult;article;autosomal recessive disorder;case report;clinical feature;disease activity;disease course;disease severity;drug effect;drug tolerability;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Bosebeck, F.",2001,,,0,0,
2351,Trientine increases fecal copper excretion in Wilson's disease: A case report,"A copper balance study was performed during the successive 7 days when a patient with Wilson's disease went on a low-copper diet and was taking 1500 mg of trientine daily. The average copper intake was 944 mug/day, urine copper excretion was 503 mug/day, fecal copper excretion was 922 mug/day; therefore, trientine reduced body copper about 500 mug per day. We provide direct evidence that trientine maintains copper balance probably by enhancing both the urinary and fecal excretion, with a larger amount decoppered in the feces. © 2001 Wiley-Liss, Inc.",D-penicillamine;Fecal copper;Taste disturbance;Trientine;Wilson's disease;adult;article;case report;clinical feature;diet;feces;female;homeostasis;human;priority journal;urinary excretion;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];trientine/dt [Drug Therapy],"Ishikawa, S.;Nomoto, S.;Yoshida, K.;Tokuda, T.;Ikeda, S. I.",2001,,http://dx.doi.org/10.1002/jtra.1051,0,0,
2352,"The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells","Angiogenesis is now recognized as a crucial process in tumor development, including hepatocellular carcinoma (HCC). Since HCC is known as a hypervascular tumor, anti-angiogenesis is a promising approach to inhibit the HCC development. Trientine dihydrochloride (trientine) is used in clinical practice as an alternative copper (Cu)-chelating agent for patients with Wilson's disease of penicillamine intolerance. In our study, we examined the effect of Cu-chelating agents on tumor development and angiogenesis in the murine HCC xenograft model. Although both trientine and penicillamine in the drinking water suppressed the tumor development, trientine exerted a more potent inhibitory effect than penicillamine. In combination with a Cu-deficient diet, both trientine and penicillamine almost abolished the HCC development. Trientine treatment resulted in a marked suppression of neovascularization and increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. In vitro studies also exhibited that trientine is not cytotoxic for the tumor cells. On the other hand, it significantly suppressed the endothelial cell proliferation. These results suggested that Cu plays a pivotal role in tumor development and angiogenesis in the murine HCC cells, and Cu-chelators, especially trientine, could inhibit angiogenesis and enhance apoptosis in the tumor with consequent suppression of the tumor growth in vivo. Since trientine is already used in clinical practice without any serious side effects as compared to penicillamine, it may be an effective new strategy for future HCC therapy. © 2001 Wiley-Liss, Inc.",Angiogenesis;Copper;Hepatocellular carcinoma;Trientine;Tumor growth;animal experiment;animal model;apoptosis;article;cancer inhibition;controlled study;dose response;endothelium cell;female;immunohistochemistry;liver cell carcinoma;nonhuman;priority journal;tumor xenograft;Wilson disease;chelating agent;drinking water;penicillamine,"Yoshii, J.;Yoshiji, H.;Kuriyama, S.;Ikenaka, Y.;Noguchi, R.;Okuda, H.;Tsujinoue, H.;Nakatani, T.;Kishida, H.;Nakae, D.;Gomez, D. E.;De Lorenzo, M. S.;Tejera, A. M.;Fukui, H.",2001,15 Dec,http://dx.doi.org/10.1002/ijc.1537,0,0,
2353,Other Parkinson syndromes,"The etiology of parkinsonism is varied. Symptomatic parkinsonism is seen in the setting of genetic disorders, infectious processes, structural lesions, and as a result of concomitant medications. A thorough history and good examination will differentiate PD from the diverse group of conditions that can mimic it.",brain function;differential diagnosis;dopamine metabolism;drug classification;epidemic encephalitis;genetic disorder;Hallervorden Spatz disease/di [Diagnosis];Hallervorden Spatz disease/et [Etiology];human;Huntington chorea/di [Diagnosis];Huntington chorea/et [Etiology];hydrocephalus/di [Diagnosis];hydrocephalus/et [Etiology];injury;Lewy body/di [Diagnosis];Machado Joseph disease/di [Diagnosis];Machado Joseph disease/et [Etiology];nuclear magnetic resonance imaging;Parkinson disease/di [Diagnosis];Parkinson disease/et [Etiology];parkinsonism/di [Diagnosis];parkinsonism/dt [Drug Therapy];parkinsonism/et [Etiology];parkinsonism/si [Side Effect];priority journal;review;single photon emission computer tomography;symptomatology;Wilson disease/di [Diagnosis];amiodarone/ae [Adverse Drug Reaction];amphotericin B/ae [Adverse Drug Reaction];calcium channel blocking agent/ae [Adverse Drug Reaction];dimercaprol/ae [Adverse Drug Reaction];dimercaprol/dt [Drug Therapy];dimercaprol/pd [Pharmacology];flunarizine/ae [Adverse Drug Reaction];fluoxetine/ae [Adverse Drug Reaction];lithium/ae [Adverse Drug Reaction];methyldopa/ae [Adverse Drug Reaction];neuroleptic agent/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pethidine/ae [Adverse Drug Reaction];procaine/ae [Adverse Drug Reaction];pyridostigmine/ae [Adverse Drug Reaction];reserpine/ae [Adverse Drug Reaction];tetrabenazine/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Colcher, A.;Simuni, T.",2001,,http://dx.doi.org/10.1016/S0733-8619%2805%2970038-4,0,0,
2354,"Copper in disorders with neurological symptoms: Alzheimer's, Menkes, and Wilson diseases","Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-beta-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer's disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer's disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer's disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology. © 2001 Elsevier Science Inc.",Alzheimer's disease;Copper;Menkes;Neurodegeneration;Wilson;akinesia;Alzheimer disease;biosynthesis;brain dysfunction;cell respiration;conference paper;depression;disease severity;dystonia;epidemiology;feeding disorder;homeostasis;human;ion transport;Menkes syndrome;mental deficiency;muscle hypotonia;nerve degeneration;neurologic disease;oxidative stress;Parkinson disease;pathology;priority journal;protein binding;reduction;seizure;Wilson disease;amyloid precursor protein/ec [Endogenous Compound];catecholamine/ec [Endogenous Compound];copper ion;cytochrome;cytochrome c oxidase/ec [Endogenous Compound];dopamine beta monooxygenase/ec [Endogenous Compound];oxygen;superoxide dismutase/ec [Endogenous Compound];water;zinc ion,"Strausak, D.;Mercer, J. F. B.;Dieter, H. H.;Stremmel, W.;Multhaup, G.",2001,15 May,http://dx.doi.org/10.1016/S0361-9230%2801%2900454-3,0,0,
2355,Wilson's disease - Differential diagnosis [2],,clinical feature;controlled study;copper metabolism;diagnostic procedure;differential diagnosis;human;laboratory test;letter;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];tetrathiomolybdic acid/dt [Drug Therapy];trientine;zinc sulfate/dt [Drug Therapy],"Koten, J.",2001,,,0,0,
2356,Wilson disease in two consecutive generations: An exceptional family [6],,adolescent;adult;ataxia;autosomal recessive disorder;case report;copper metabolism;female;genetic analysis;heterozygote;human;letter;liver transplantation;male;pedigree analysis;point mutation;polymerase chain reaction;priority journal;restriction fragment length polymorphism;tremor;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Firneisz, G.;Szonyi, L.;Ferenci, P.;Gorog, D.;Nemes, B.;Szalay, F.",2001,,http://dx.doi.org/10.1016/S0002-9270%2801%2902546-1,0,0,
2357,Mitochondria and degenerative disorders,"In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities. © 2001 Wiley-Liss, Inc.",Alzheimer disease;Amyotrophic lateral sclerosis;Friedreich ataxia;Hereditary spastic paraparesis;Huntington disease;Mitochondria;Neurodegenerative disorders;Parkinson disease;Wilson disease;Alzheimer disease/et [Etiology];amyotrophic lateral sclerosis/et [Etiology];apoptosis;article;calcium homeostasis;degenerative disease/et [Etiology];energy metabolism;external ophthalmoplegia/et [Etiology];Friedreich ataxia/et [Etiology];gene mutation;human;Huntington chorea/et [Etiology];Leigh disease/et [Etiology];nonhuman;oxidative phosphorylation;Parkinson disease/et [Etiology];priority journal;spastic paraplegia/et [Etiology];Wilson disease/et [Etiology];cell protein/ec [Endogenous Compound];frataxin/ec [Endogenous Compound];free radical/ec [Endogenous Compound];huntingtin/ec [Endogenous Compound];mitochondrial DNA/ec [Endogenous Compound];paraplegin/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound],"Orth, M.;Schapira, A. H. V.",2001,,http://dx.doi.org/10.1002/ajmg.1425,0,0,
2358,Common metabolic diseases of the liver,"Metabolic diseases of the liver range from among the commonest of all metabolic diseases, haemochromatosis, to the extremely rare. The histopathologist plays a central role in raising the possibility and confirming the diagnosis. This involves careful analysis of the biopsy and the appropriate use of special stains and biochemical analyses. The commonest metabolic diseases seen in routine practice are haemochromatosis, Wilson's disease and alpha-1 antitrypsin deficiency and these are discussed in this article.",Alpha-1 antitrypsin deficiency;Haemochromatosis;Wilson's disease;alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/et [Etiology];clinical feature;diagnostic value;hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];histopathology;human;laboratory personnel;liver biopsy;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];review;staining;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];alpha 1 antitrypsin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Goldin, R. D.",2001,,,0,0,
2359,"An adolescent with haemolytic anaemia and coagulation disorders as manifestations of Wilson's disease, treated by liver transplantation. [Dutch]","A 16-year-old woman presented with anaemia, jaundice, vomiting and nosebleed. She had acute hepatic failure and haemolytic anaemia and developed acute respiratory distress syndrome (ARDS). Wilson's disease was diagnosed. After the ARDS resolved the patient underwent a successful orthotopic liver transplantation. Diagnostic combinations for Wilson's disease are ceruloplasmin < 0.2 g/l with Kayser-Fleischer rings, liver copper > 250 mug/g (dry weight) with Kayser-Fleischer rings, or homozygosity for a Wilson mutation on the 13th chromosome. In acute liver failure a copper excretion in 24 h-urine above 1 mg is diagnostic for Wilson's disease, while an elevated serum copper concentration makes this diagnosis very likely. Therapeutic options for Wilson's disease are chelation therapy and liver transplantation; in most cases of acute liver failure due to Wilson's disease orthotopic liver transplantation (preceded by albumin dialysis) is indicated. Nazer's index should be used in addition to the regular King's College criteria for liver transplantation indication.",adolescent;adult respiratory distress syndrome/co [Complication];article;blood clotting disorder/co [Complication];case report;chelation;copper blood level;female;hemolytic anemia/co [Complication];human;liver failure/co [Complication];liver failure/su [Surgery];liver toxicity/et [Etiology];liver transplantation;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];corticosteroid/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Brouwer, R. E.;Manten, A.;Van Leeuwen, A. M.;Veenendaal, R. A.;Ringers, J.;Van Hoek, B.",2001,17 Feb,,0,0,
2360,"ABC of diseases of liver, pancreas, and biliary system: Other causes of parenchymal liver disease",,autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];drug induced disease/et [Etiology];hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];hemochromatosis/th [Therapy];human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/su [Surgery];obstructive jaundice/di [Diagnosis];obstructive jaundice/et [Etiology];primary biliary cirrhosis/di [Diagnosis];primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/di [Diagnosis];primary sclerosing cholangitis/dt [Drug Therapy];primary sclerosing cholangitis/et [Etiology];primary sclerosing cholangitis/su [Surgery];priority journal;review;toxic hepatitis/dt [Drug Therapy];toxic hepatitis/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];acetylcysteine/dt [Drug Therapy];azathioprine/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration],"Ryder, S. D.;Beckingham, I. J.",2001,03 Feb,,0,0,
2361,Oral zinc therapy in patients with supposed mild zinc deficiency - A critical review,The importance of zinc in many processes of diseases remains unclear up today. Nevertheless many biochemical or clinical studies let support a high clinical relevance of trace elements especially zinc in the therapeutic concepts of diseases. Unfortunately the border between severe (or real) and mild (or subclinical) zinc deficiency is not clear defined. In addition methodical problems in determination of trace elements and misinterpretations of study results lead to unjustified assignment from several diseases in the group of zinc deficiency disorders. Another current problem is the consideration of bioavailability of oral commercial trace element products. Especially the regulation of zinc uptake in human under normal conditions and in case of zinc deficiency is not clear at this time. These problems let become tangled the actual literature for the clinical active physician at the field of zinc. In this mini review there is given an overview about published clinical studies with oral zinc supplementation in the past years.,Oral Therapy;Review;Zinc;Zinc Deficiency;acne vulgaris/dt [Drug Therapy];drug bioavailability;duodenum ulcer/dt [Drug Therapy];stomach ulcer/dt [Drug Therapy];treatment indication;vitamin supplementation;Wilson disease/dt [Drug Therapy];zinc deficiency/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc/pk [Pharmacokinetics],"Hocke, M.;Winnefeld, K.;Bosseckert, H.",2001,,http://dx.doi.org/10.1055/s-2001-10709,0,0,
2362,The impact of penicillamine and zinc in hepatic and brain tissues of copper-overloaded rats,"Objective: The aim of this study is to evaluate the efficacy of penicillamine and zinc sulphate in copper-loaded rats and to compare the copper reduction in hepatic and brain tissues. Material and methods: Thirty-five male albino Wistar rats were equally divided into 5 groups. The control group (G1) was given normal tap water, while the 4 groups (G2, 3, 4, 5) were supplied with copper-loaded water. After 5 weeks, rats in G1 and G2 were sacrificed. The remaining rats (G3, 4, 5) were given normal diet for the following 4 weeks. During that period, the fourth group (G4) was given zinc sulphate (6.5 mg/kg) and the fifth group (G5) received penicillamine (20 mg/kg). The third group (G3) was left untreated. Results: Amounts of copper deposited in hepatic tissues of G2 were significantly higher than G1 (p = 0.008). In G3, brain copper levels were significantly higher than G1 and G2 (p < 0.001 and 0.01, respectively), while hepatic concentrations were not statistically different. Rats in G5 had significantly lower hepatic and brain copper levels than G3 (p = 0.023 and < 0.001, respectively). There was a significant reduction in brain copper levels in G4, as compared to G3 (p = 0.003). Conclusion: The reduction of copper levels in both hepatic and brain tissues with penicillamine in copper-overloaded rats suggests that other mechanisms than the redistributive effect in the brain may be responsible for the neurologic deterioration induced by penicillamine treatment in patients with WD. Furthermore, zinc may have an early effect in prevention of excess copper deposition, probably by inducing metallothionin synthesis in the liver. In conclusion, zinc may be used in conjunction with chelating agents for the initial control of patients with neurologic symptoms.",Copper overload;Efficacy;Penicillamine;Zinc;animal experiment;animal model;animal tissue;article;brain tissue;controlled study;drug effect;liver;male;nonhuman;priority journal;protein synthesis;rat;reduction;Wilson disease/dt [Drug Therapy];copper;metallothionein;penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Ozcelik, D.;Eralp, Y.;Oztekin, G.;Dursun, S.;Uzunismail, H.",2001,,,0,0,
2363,The Wilson's disease gene and phenotypic diversity,,animal model;chelation therapy;gene mutation;genetic analysis;genetic heterogeneity;human;liver cell carcinoma/et [Etiology];liver cell carcinoma/pc [Prevention];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver transplantation;mental disease/co [Complication];neurologic disease/co [Complication];nonhuman;phenotype;priority journal;rat;review;screening test;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin;copper;manganese;penicillamine/dt [Drug Therapy],"Riordan, S. M.;Williams, R.",2001,,http://dx.doi.org/10.1016/S0168-8278%2800%2900028-3,0,0,
2364,Iatrogenic copper deficiency associated with long-term copper chelation for treatment of copper storage disease in a Bedlington Terrier,"Copper storage disease in Bedlington Terriers is an autosomal recessive inherited defect of biliary excretion that results in hepatic copper accumulation and hepatic injury. Treatment of copper storage disease involves the use of dietary copper restriction and a copper chelator or zinc acetate to prevent copper absorption. Prolonged treatment with a chelator, particularly in a heterozygous carrier with high hepatic copper concentration, has the potential to result in copper deficiency. Copper deficiency associated with overtreatment should be considered in dogs receiving chelation treatment that have microcytosis or evidence of liver dysfunction.",animal model;article;chelation;copper deficiency/co [Complication];copper deficiency/di [Diagnosis];dietary intake;dog;iron deficiency/co [Complication];iron deficiency/di [Diagnosis];liver biopsy;male;nonhuman;storage disease/cn [Congenital Disorder];storage disease/di [Diagnosis];storage disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];copper/dt [Drug Therapy];copper/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];trientine/do [Drug Dose],"Seguin, M. A.;Bunch, S. E.",2001,15 May,,0,0,
2365,Metabolic liver disease,"The discovery of novel metabolic pathways and the genetic basis for diseases of the liver continues to yield new insights into the pathogenesis of inherited metabolic diseases of the liver, whereas the application of new technologies to their treatment continues to advance therapeutic options. This review of selected articles covers a wide range of subjects, from the identification of novel proteins and transport pathways to disease diagnosis and treatment of acute liver failure. Four selected topics, Wilson disease, hemochromatosis and iron overload disorders, alpha-1 antitrypsin disease, and exciting new therapeutic options for lysosomal storage diseases are the focus of this review. © 2001 Lippincott Williams & Wilkins, Inc.",alpha 1 antitrypsin deficiency/et [Etiology];alpha 1 antitrypsin deficiency/su [Surgery];cell transport;clinical trial;enzyme replacement;Fabry disease/di [Diagnosis];Fabry disease/dt [Drug Therapy];Gaucher disease/di [Diagnosis];Gaucher disease/dt [Drug Therapy];gene mutation;hemochromatosis/et [Etiology];human;iron overload/et [Etiology];liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/su [Surgery];liver transplantation;lysosome storage disease/di [Diagnosis];lysosome storage disease/dt [Drug Therapy];meta analysis;metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];metabolic disorder/su [Surgery];mucopolysaccharidosis/di [Diagnosis];mucopolysaccharidosis/dt [Drug Therapy];nonhuman;pathogenesis;review;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];adenosine triphosphatase/ec [Endogenous Compound];alglucerase/do [Drug Dose];alglucerase/dt [Drug Therapy];alpha galactosidase/ct [Clinical Trial];alpha galactosidase/do [Drug Dose];alpha galactosidase/dt [Drug Therapy];alpha galactosidase/iv [Intravenous Drug Administration];alpha glucosidase/ct [Clinical Trial];alpha glucosidase/dt [Drug Therapy];apolipoprotein E/ec [Endogenous Compound];beta glucosidase/dt [Drug Therapy];biochemical marker/ec [Endogenous Compound];ceramide glucosyltransferase inhibitor/dt [Drug Therapy];ceramide glucosyltransferase inhibitor/po [Oral Drug Administration];glucosylceramidase/do [Drug Dose];glucosylceramidase/dt [Drug Therapy];levo iduronidase/ct [Clinical Trial];levo iduronidase/dt [Drug Therapy];membrane protein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];sphingolipid activator protein 2/ec [Endogenous Compound];transferrin receptor/ec [Endogenous Compound];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Schilsky, M. L.;Mistry, P.",2001,,http://dx.doi.org/10.1097/00001574-200105000-00005,0,0,
2366,Inherited metabolic disease,"This review focuses on two genetic disorders of metal metabolism, genetic hemochromatosis and Wilson disease, and on the most common lysosomal storage disorder, Gaucher disease, for which recombinant enzyme replacement therapy is available. The discovery of the genes for these disorders has led to an explosion of new information about the function of these gene products and the identification of other proteins involved in their metabolism. These discoveries have altered our current diagnostic and therapeutic approaches to these disorders and have furthered our understanding of disease pathophysiology. New modalities being developed for future use include cell transplant and genetic replacement therapies. © 2000 Lippincott Williams & Wilkins, Inc.",clinical trial;enzyme replacement;Gaucher disease/di [Diagnosis];Gaucher disease/dt [Drug Therapy];Gaucher disease/et [Etiology];gene mutation;genetic analysis;genetic disorder/di [Diagnosis];genetic disorder/dt [Drug Therapy];genetic disorder/et [Etiology];hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];human;liver toxicity/si [Side Effect];metal metabolism;neurotoxicity/si [Side Effect];pathophysiology;protein analysis;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alglucerase;glucosylceramidase/dt [Drug Therapy];imiglucerase/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Schilsky, M. L.;Mistry, P.",2000,,http://dx.doi.org/10.1097/00001574-200005000-00004,0,0,
2367,Wilson's disease,"During the last 90 years, Wilson's hepatolenticular degeneration has evolved from a disease presenting insurmountable challenges to the clinician's diagnostic acumen to a metabolic disorder which is diagnosable with certainty, treatable successfully, and even preventable. It may not be long before the genetic defect becomes amenable to correction and a cure of the disease becomes possible.",bile duct carcinoma/co [Complication];clinical feature;diagnostic procedure;diet;drug induced disease/si [Side Effect];gene therapy;genetics;hepatitis/co [Complication];histopathology;human;liver cell carcinoma/co [Complication];liver failure/co [Complication];liver transplantation;neurologic disease/co [Complication];pathophysiology;pregnancy;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];thiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/do [Drug Dose];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Sternlieb, I.",2000,,,0,0,
2368,Histochemical characterization of silver-induced metallothionein in rat kidney,"Histochemical characterizations of Ag-induced metallothionein (MT) in the kidney of the rat have been reported. Ag, Cu and Zn contents increased in kidney and liver after Ag injection. In particular, the Cu content in kidneys increased dramatically after three injections of Ag. Sephadex G-75 elution profiles of the renal cytosol of rats injected with Ag revealed that the accumulated Cu in the kidney was bound to MT as were Ag and Zn. In addition, localization of Cu- and Ag-MT in the kidney was studied using autofluorescent signals, which are dependent on Cu- or Ag-thiol clusters, and immunohistochemistry. Although the MT induced by Ag was predominantly observed in the cortex of the kidney, some MT signals were also detected in the outer stripe of the outer medulla, as well as in the kidneys of LEC rats, an animal model of Wilson disease (a hereditary disorder of Cu metabolism). In these LEC rats, the Cu-MT also accumulated in the outer stripe of the outer medulla of the kidney. From these results, one possibility could explain that the Cu-MT detected in the outer stripe of the outer medulla in the kidney of Ag-injected rat was associated with the Cu transporter affected by Ag. Copyright (C) 2000 Elsevier Science Inc.",atp7b;Copper;Kidney;Metallothionein;Silver;animal experiment;animal model;animal tissue;article;autofluorescence;controlled study;histochemistry;immunohistochemistry;liver;male;Menkes syndrome/et [Etiology];nonhuman;protein localization;rat;tissue level;Wilson disease/et [Etiology];copper/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Kurasaki, M.;Okabe, M.;Saito, S.;Yamanoshita, O.;Hosokawa, T.;Saito, T.",2000,31 Mar,http://dx.doi.org/10.1016/S0162-0134%2800%2900054-4,0,0,
2369,A young adult female case of Wilson's disease presenting with mental disorder and frontal lobe signs. [Japanese],"We report a young adult female case of Wilson's disease presenting with mental disorder and frontal lobe signs. The patient was admitted to our neurological unit on October 4, 1999 because of schizophrenia-like symptom, dysphagia, dysarthria and gait disturbance. She showed slowly progressive rigidity and dystonia. Her parents were the second cousins. Neurological examination revealed bilateral pyramidal and extrapyramidal signs, frontal lobe signs (include the imitation behavior). Tendon reflexes were slightly exaggerated in all extremities. Bilateral Babinski, Chaddock and Hoffmann signs were positive. Her verbal IQ on the Wechsler Adult Intelligence Scale-revised was 49. Biochemical examination revealed low plasma copper and ceruloplasmin concentration. Cerebrospinal fluid was normal. Cranial MRI demonstrated diffuse brain atrophy and enlargement of the lateral ventricles. T<inf>2</inf>-weighted images of the MRI demonstrated hyperintense signal in both thalamus and basal ganglia. SPECT showed hypoperfusion in the left frontal lobe, both thalamus and basal ganglia. EEG revealed diffuse 2q wave. The diagnosis of Wilson's disease was made and the treatment of D-penicillamine 900mg per day was started. This hypoperfusion of SPECT and EEG findings improved after 2 months under D-penicillamine therapy. Neurological findings showed slight improvement. A few Wilson's disease patients presenting with mental disorder have been reported. Wilson's disease should always be considered in differential diagnosis of mental disorders. We emphasize the importance of early diagnosis and treatment of Wilson's disease.",Frontal lobe sign;Imitation behavior;Mental disorder;mri;Wilson's disease;adult;article;case report;diagnostic imaging;differential diagnosis;dysarthria;dysphagia;early diagnosis;extrapyramidal symptom;female;frontal lobe;gait disorder;human;mental disease;rigidity;schizophrenia;tendon reflex;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Iwasaki, Y.;Sone, M.;Kato, T.;Yoshida, E.",2000,,,0,0,
2370,Visual pathway abnormalities Wilson's diseasean electrophysiological study using electroretinography and visual evoked potentials,"The pathogenesis of the pattern reversal visual evoked potential (PRVEP) abnormalities in patients with Wilson's disease (WD) has not been investigated earlier. Since electroretinography (ERG) assesses the functional integrity of the retina, it was used along with PRVEP to localize the abnormalities in PRVEP in Wilson's patients. Ten newly diagnosed Wilson's disease patients underwent PRVEP and flash ERG soon after the diagnosis was established. The PRVEP latencies were prolonged in comparison with the controls (P<0.001). Photopic and scotopic A waves and oscillatory potentials were prolonged (P<0.02) with reduction in amplitudes of photopic A and B waves (P<0.001). Six of these patients were subjected to repeat PRVEP and flash ERG after the clinical improvement with specific therapy. Comparison of the pre and post-treatment visual electrophysiological studies revealed significant reduction in latencies of PRVEP and flash ERG A wave (P<0.05) with increase in amplitudes of P100 of PRVEP (P<0.05), A and B waves of flash ERG (P<0.01). These findings confirm the reported PRVEP changes in WD and in addition demonstrate the reversibility of the retinal dysfunction which partially contributes to the PRVEP abnormalities. To the best of our knowledge this is the first study of ERG in patients with Wilson's disease in the literature. Further, there have been no earlier reports in the literature evaluating the effect of specific treatment on the PRVEP and ERG in Wilson's disease. Copyright (C) 2000 Elsevier Science B.V.",Flash electroretinography;Visual evoked potentials;Wilson's disease;adolescent;adult;article;child;clinical article;electroretinography;evoked visual response;female;human;male;night vision;oscillatory potential;priority journal;retina disease;visual disorder/et [Etiology];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];potassium sulfide/dt [Drug Therapy];unclassified drug;zinc sulfate/dt [Drug Therapy],"Satishohandra, P.;Ravishankar Naik, K.",2000,01 May,http://dx.doi.org/10.1016/S0022-510X%2800%2900280-X,0,0,
2371,Comparative efficacy of several potential treatments for copper mobilization in copper-overloaded rats,"D-Penicillamine (DPA) is effective in the treatment of Wilson's disease, whereas zinc salts are also used as a therapy for this disorder of copper transport. Recently, it has been shown that the copper chelators 1,4,7,11- tetraazaundecane tetrahydrochloride (TAUD) and tetraethylenepentamine pentahydrochloride (TETREN) could be useful for copper mobilization in rats. Because these agents could be potential clinical alternatives to DPA for patients with Wilson's disease who are intolerant to this drug, we examined whether oral administration of TAUD and TETREN could be effecting in mobilizing copper in experimental copper-overloaded rats. The efficacy of a combined administration of zinc and DPA, TAUD, or TETREN was also assessed. Rats were copper loaded with 0.125% copper acetate in water for 12 wk. After this period, DPA, TAUD, and TETREN were administered by gavage at 0.67 mmol/kg/d for 5 d, and zinc was given at 2.5 mg Zn/kg/d. Twelve weeks of copper loading resulted in a 32-fold increase in total hepatic copper. TETREN was the most effective chelator in increasing the urinary excretion of copper. However, it did not reduce significantly the hepatic copper levels. In turn, combined administration of zinc and chelating agents significantly reduced the amount of copper found in the feces. Although TAUD and TETREN showed a similar or higher efficacy to DPA in mobilizing copper, concurrent treatment of chelating agents and zinc salts should be discarded according to the current results.","Chelating agents;Copper;Copper excretion;Overloaded rats;Tissue copper distribution;Zinc acetate;animal experiment;animal model;article;controlled study;copper blood level;drug efficacy;drug mechanism;drug mixture;hepatitis;liver cirrhosis;liver fibrosis;male;neurologic disease;nonhuman;rat;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];1,4,7,11 tetraazaundecane tetrahydrochloride/cb [Drug Combination];1,4,7,11 tetraazaundecane tetrahydrochloride/cm [Drug Comparison];1,4,7,11 tetraazaundecane tetrahydrochloride/dv [Drug Development];1,4,7,11 tetraazaundecane tetrahydrochloride/po [Oral Drug Administration];1,4,7,11 tetraazaundecane tetrahydrochloride/pd [Pharmacology];chelating agent/cb [Drug Combination];chelating agent/cm [Drug Comparison];chelating agent/dv [Drug Development];chelating agent/po [Oral Drug Administration];chelating agent/pd [Pharmacology];copper acetate/to [Drug Toxicity];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];tetraethylenepentamine pentahydrochloride/cb [Drug Combination];tetraethylenepentamine pentahydrochloride/cm [Drug Comparison];tetraethylenepentamine pentahydrochloride/dv [Drug Development];tetraethylenepentamine pentahydrochloride/po [Oral Drug Administration];tetraethylenepentamine pentahydrochloride/pd [Pharmacology];unclassified drug;zinc acetate/cb [Drug Combination];zinc acetate/dv [Drug Development];zinc acetate/dt [Drug Therapy];zinc derivative/cb [Drug Combination];zinc derivative/dv [Drug Development];zinc derivative/dt [Drug Therapy]","Domingo, J. L.;Gomez, M.;Jones, M. M.",2000,,,0,0,
2372,Cyproterone for hypersexuality in a psychotic patient with Wilson's disease [9],,adult;affective neurosis;behavior disorder;case report;clinical feature;cognitive defect;delusion/dt [Drug Therapy];disease course;exhibitionism;human;letter;male;mental patient;personality disorder/dt [Drug Therapy];psychosis;sexual dysfunction/dt [Drug Therapy];sexuality;symptom;Wilson disease/dt [Drug Therapy];antiandrogen/dt [Drug Therapy];chelating agent/dt [Drug Therapy];cyproterone acetate/dt [Drug Therapy];haloperidol/cb [Drug Combination];haloperidol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];periciazine/cb [Drug Combination];periciazine/dt [Drug Therapy];zinc citrate/dt [Drug Therapy],"Volpe, F. M.;Tvares, A.",2000,,http://dx.doi.org/10.1046/j.1440-1614.2000.0822l.x,0,0,
2373,Diagnosis of Wilson's disease: An experience over three decades,"Background - Wilson's disease is a rare but treatable condition that often presents diagnostic dilemmas. These dilemmas have for the most part not been resolved by the identification and cloning of the Wilson's disease gene. Aims - To report our experience over three decades with patients with Wilson's disease in order to illustrate the diverse patterns of presentation and thereby broaden the approach to diagnosis. Methods - Clinical and laboratory findings of 30 patients with Wilson's disease were reviewed. Results - Twenty two patients presented with liver manifestations (eight with fulminant hepatic failure and 14 with chronic liver disease), three with neurological disease, and one with haemolysis; four were asymptomatic siblings of patients with Wilson's disease. Seventy per cent were diagnosed within six months of the onset of symptoms, but diagnosis was delayed for up to nine years. Age range at diagnosis was wide (7-58 years) and five patients were over 40. In patients presenting with non-fulminant disease, 18% had neither Kayser-Fleischer rings nor low caeruloplasmin concentrations. Increased liver copper concentrations were found in all but one patient who had undergone six years of penicillamine treatment. In fulminant hepatic failure (n=8) additional features helpful in the diagnosis included evidence of haemolysis, increased urinary copper (range 844-9375 mug/24 h), and a high non-caeruloplasmin copper (range 325-1743 mug/l). Conclusions - The diagnosis of Wilson's disease still depends primarily on the evaluation of clinical and laboratory evidence of abnormal copper metabolism. No one feature is reliable, but the diagnosis can usually be made provided that it is suspected. Wilson's disease should be considered in patients of any age with obscure hepatic or neurological abnormalities.",Diagnosis;Fulminant hepatic failure;Liver;Wilson's disease;adolescent;adult;article;child;chronic liver disease;clinical article;clinical feature;copper metabolism;female;hemolysis;human;liver failure;male;molecular cloning;neurologic disease;priority journal;Wilson disease/di [Diagnosis];ceruloplasmin;penicillamine,"Gow, P. J.;Smallwood, R. A.;Angus, P. W.;Smith, A. L.;Wall, A. J.;Sewell, R. B.",2000,,http://dx.doi.org/10.1136/gut.46.3.415,0,0,
2374,"Wilson's disease: Challenging diagnosis, management, and liver transplantation timing",,adult;chronic hepatitis;clinical article;clinical feature;conference paper;fatty liver;female;hemolysis;human;liver cirrhosis;liver fibrosis;liver transplantation;male;neurologic disease;priority journal;treatment indication;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Macedo, G.;Maia, J. C.;Gomes, A.;Amil, J.;Fernandas, N.;Carneiro, F.;Teixeira, A.;Ribeiro, T.",2000,,http://dx.doi.org/10.1016/S0041-1345%2800%2901834-0,0,0,
2375,High performance liquid chromatography analysis of D-penicillamine by derivatization with N-(1-pyrenyl) maleimide (NPM),"D-Penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), a well-known heavy metal chelator, is the drug of choice in the treatment of Wilson's disease and is also effective for the treatment of several disorders including rheumatoid arthritis, primary biliary cirrhosis, scleroderma, fibrotic lung diseases and progressive systemic sclerosis. The method proposed incorporates a technique, previously developed in our laboratory, that utilizes the derivatizing agent N-(1-pyrenyl)maleimide (NPM) and reversed-phase high-performance liquid chromatography (HPLC). The coefficients of variation for within-run precision and between-run precision for 500 nM standard D-penicillamine (D-pen) were 2.27% and 2.23%, respectively. Female Sprague-Dawley rats were given 1 g/kg D-pen i.p. and the amounts of D-pen in liver, kidney, brain and plasma were subsequently analyzed. This assay is rapid, sensitive and reproducible for determining D-pen in biological samples. Copyright © 2000 John Wiley & Sons, Ltd.",animal experiment;animal model;animal tissue;article;chelation;controlled study;derivatization;diagnostic accuracy;drug blood level;drug brain level;drug determination;drug efficacy;drug liver level;drug tissue level;female;high performance liquid chromatography;kidney;laboratory;lung fibrosis/dt [Drug Therapy];male;methodology;nonhuman;partition coefficient;primary biliary cirrhosis/dt [Drug Therapy];rat;reproducibility;reversed phase high performance liquid chromatography;rheumatoid arthritis/dt [Drug Therapy];scleroderma/dt [Drug Therapy];systemic sclerosis/dt [Drug Therapy];variance;Wilson disease/dt [Drug Therapy];chelating agent/an [Drug Analysis];chelating agent/cr [Drug Concentration];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];maleimide derivative;n (1 pyrenyl)maleimide;penicillamine/an [Drug Analysis];penicillamine/cr [Drug Concentration];penicillamine/dt [Drug Therapy];penicillamine/ip [Intraperitoneal Drug Administration];penicillamine/pd [Pharmacology];unclassified drug,"Mroczek, T.;Glowniak, K.;Hajnos, M.",2000,,http://dx.doi.org/10.1002/1099-0801%28200012%2914:8%3C535::AID-BMC11%3E3.0.CO;2-G,0,0,
2376,Treatment of Wilson's disease with zinc. XVII: Treatment during pregnancy,"Therapy of Wilson's disease continues to evolve. In 1997, zinc acetate was added to the list of drugs approved by the Food and Drug Administration, which includes penicillamine and trientine. The mechanism of zinc's anticopper action is unique. It induces intestinal cell metallothionein, which binds copper and prevents its transfer into blood. As intestinal cells die and slough, the contained copper is eliminated in the stool. Thus, zinc prevents the intestinal absorption of copper. It is universally agreed that pregnant Wilson's disease patients should remain on anticopper therapy during pregnancy. There are numerous reports of such patients stopping penicillamine therapy to protect their fetus from teratogenicity, only to undergo serious deterioration and even death from renewed copper toxicity. Penicillamine and trientine have teratogenic effects in animals, and penicillamine has known teratogenic effects in humans. In this report we discuss the results of 26 pregnancies in 19 women who were on zinc therapy throughout their pregnancy. The evidence is good that zinc protects the health of the mother during pregnancy. Fetal outcomes were generally quite good, although one baby had a surgically correctable heart defect and one had microcephaly.",adult;article;childbirth;clinical article;copper blood level;drug efficacy;drug safety;female;human;liver function test;maternal welfare;neurologic examination;pregnancy disorder/dt [Drug Therapy];priority journal;teratogenicity;urine level;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine;trientine;zinc/dt [Drug Therapy],"Brewer, G. J.;Johnson, V. D.;Dick, R. D.;Hedera, P.;Fink, J. K.;Kujin, K. J.",2000,,,0,0,
2377,"Fifth Meeting of International Society of Trace Element Research in Humans, Lyon, France, 1998: Trace elements in human health and disease: An update",,cellular immunity;cognition;diet therapy;editorial;enteritis/et [Etiology];growth;health;hepatic encephalopathy/et [Etiology];iodine deficiency/et [Etiology];iron metabolism;motor neuron disease/et [Etiology];priority journal;symposium;Wilson disease/et [Etiology];arsenic/to [Drug Toxicity];cadmium/to [Drug Toxicity];metallothionein/ec [Endogenous Compound];trace element/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Prasad, A. S.",2000,,http://dx.doi.org/10.1002/%28SICI%291520-670X%282000%2913:1%3CI::AID-JTRA1%3E3.0.CO;2-S,0,0,
2378,Raulin Award Lecture: Wilson's disease therapy with zinc and tetrathiomolybdate,"Zinc and tetrathiomolybdate, effective, nontoxic drugs, have now been added to the treatment of most phases of Wilson's disease. Zinc is used for maintenance as well as treating presymptomatic, pregnant, and pediatric patients. Tetrathiomolybdate is the choice for patients presenting with neurologic diseases. (C) 2000 Wiley-Liss, Inc.",Copper homeostasis;Tetrathiomolybdate;Wilson's disease;Zinc;conference paper;homeostasis;human;neurologic disease/co [Complication];neurologic disease/dt [Drug Therapy];pregnancy;priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Brewer, G. J.",2000,,http://dx.doi.org/10.1002/%28SICI%291520-670X%282000%2913:1%3C51::AID-JTRA7%3E3.0.CO;2-A,0,0,
2379,Elastoma perforating serpiginous and pseudo-xanthoma elasticum after D-penicillamine treatment. [French],"One case is described in a 47-year-old man treated with D-penicillamine during 20 years. Small horny papules, which are arranged in a serpiginous pettern occurred in the right axillary fold then on the rightshoulder and the neck. Histology showed an epidermal hyperplasia traverses by a channel. Moreover, there were yellowish papules whose biopsy revealed abnormal tangled elastitic fibers in dermis. D-penicillamine can be considered as a toxic drug destroying elastic fibers. The association of elastoma perforating serpiginous and pseudoxanthoma elasticum is uncommon.",Elastoma perforating;Penicillamine;Pseudoxanthoma;Serpiginous;adult;case report;conference paper;dermis;drug induced disease/si [Side Effect];elastic fiber;histology;human;human tissue;male;papule;pseudoxanthoma elasticum/di [Diagnosis];pseudoxanthoma elasticum/et [Etiology];pseudoxanthoma elasticum/si [Side Effect];skin biopsy;skin disease/di [Diagnosis];skin disease/et [Etiology];skin disease/si [Side Effect];Wilson disease/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Bourgeois-Droin, C.;Fouchard, N.;Pedreiro, J.",2000,,,0,0,
2380,Oxidative-phosphorylation defects in liver of patients with Wilson's disease,"Background. Wilson's disease (WD) is caused by mutations in a P-type ATPase and is associated with copper deposition in liver and brain. The WD protein is present in the trans-Golgi network and may also be imported into mitochondria. The WD protein functions as a P-type copper transporting ATPase in the Golgi but any action in mitochondria is at present unknown. Methods. We studied mitochondrial function and aconitase activity in WD liver tissue and compared the results with those in a series of healthy controls and patients without WD. Findings. There was evidence of severe mitochondrial dysfunction in the livers of patients with WD. Enzyme activities were decreased as follows: complex I by 62%, complex II + III by 52%, complex IV by 33%, and aconitase by 71%. These defects did not seem to be secondary to penicillamine use, cholestasis, or poor hepatocellular synthetic function. Interpretation. The results show that there is a defect of energy metabolism in WD. The pattern of enzyme defects suggests that free-radical formation and oxidative damage, probably mediated via mitochondrial copper accumulation, are important in WD pathogenesis. These results provide a rationale for a study of the use of antioxidants in WD.",adolescent;adult;article;case report;controlled study;energy metabolism;enzyme activity;female;gene mutation;Golgi complex;human;human cell;human tissue;male;oxidative phosphorylation;priority journal;school child;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];aconitate hydratase/ec [Endogenous Compound];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];citrate synthase/ec [Endogenous Compound];copper/ec [Endogenous Compound];free radical/ec [Endogenous Compound];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Gu, M.;Cooper, J. M.;Butler, P.;Walker, A. P.;Mistry, P. K.;Dooley, J. S.;Schapira, A. H. V.",2000,05 Aug,,0,0,
2381,Kayser-Fleischer corneal ring,,adult;article;case report;copper blood level;gaze paralysis/co [Complication];human;male;priority journal;tremor/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Heckmann, J. G.;Lang, C. J. G.;Neudorfer, B.;Kuchle, M.",2000,,,0,0,
2382,Massive hepatic haemosiderosis in Wilson's disease,,adult;animal experiment;animal model;blood analysis;case report;copper metabolism;hemosiderosis/di [Diagnosis];hemosiderosis/et [Etiology];histopathology;human;iron metabolism;letter;nonhuman;priority journal;rat;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];hemosiderin/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Luca, P.;Demelia, L.;Lecca, S.;Ambu, R.;Faa, G.",2000,,,0,0,
2383,Wilson's disease revisited. [Serbian],"Wilson's disease is an autosomal recessive disorder characterized by an inability of the liver to excrete copper into bile and to incorporate copper into ceruloplasmin. Gradual accumulation of copper in various tissues causes dysfunction of organs so that untreated disease is invariably fatal. Because the manifestations of Wilson's disease are protean and the disease masquerades so well as something else, recognition of the possibility of Wilson's disease is a major problem leading to serious underdiagnosis of the disease. The longer recognition and diagnosis are delayed, the greater the risk of permanent damage primarily to liver and/or brain. The availability of effective therapy and the risk in delay of therapy make the earlies possible diagnosis critical. Current therapies include chelators that increase urinary excretion of copper and tetrathiomolybdate which complexes with copper and blocks copper absorption from the intestine or renders blood cooper nontoxic. In cases of liver failure, liver transplantation is effective treatment. The diagnostic and therapeutic algorithms are discussed.",Hepatolenticular degeneration - drug therapy;Zinc - therapeutic use;copper metabolism;human;liver transplantation;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Vucelic, B.",2000,,,0,0,
2384,Zinc as initial treatment of Wilson's disease in children. [Serbian],"Wilson's disease (WD) is an inherited disease of copper accumulation, caused by a failure of biliary excretion of excess copper. Accumulated copper causes tissue damage. The chelating drugs penicillamine and trientine have been the mainstay of therapy and most patients with WD were treated with the potentially toxic cupriuretic agents. A more recent approach has used zinc, which blocks the absorption of copper and increases copper excretion in the stool, and long term administration induces a negative copper balance. Until recently, most patients have been treated initially with cupriuretic agents to remove excess of copper, and then maintained with oral zinc. Recently, zinc has been used for initial treatment as well and for treatment of the presymptomatic patients. So far, zinc therapy has demonstrated exceptional efficacy and lack of toxicity. In this article we present our data on the long-term follow-up of three children with WD, whose initial as well as consecutive treatment was zinc sulphate. The results demonstrate the efficacy of zinc therapy in treating the presymptomatic patient and in initial treatment of symptomatic children with WD. Our data also indicate low toxicity. However, pediatric patients must be closely monitored due to tendency to stop the treatment when becoming asymptomatic.",Hepatolenticular degeneration - drug therapy;Zinc - therapeutic use;adolescent;article;case report;follow up;human;male;school child;treatment outcome;Wilson disease/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Cacic, M.;Percl, M.;Jadresin, O.;Kolacek, S.",2000,,,0,0,
2385,Novel mutations of the ATP7B gene in Japanese patients with Wilson disease,"Wilson disease (WD) is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and corneas, and culminating in copper toxication in these organs. In this study, we analyzed mutations of the responsible gene, ATP7B, in four Japanese patients with WD. By direct sequencing, we identified five mutations, of which two were novel, and 16 polymorphisms, of which 6 were novel. The mutations 2871delC and 2513delA shift the reading frame so that truncated abnormal protein is expected. In contrast to these mutations found in patients with hepatic-type of early onset, the mutations A874V, R778L, and 3892delGTC were either missense mutations or inframe 1-amino acid deletion, and occurred in the patients with hepato-neurologic type of late onset. The mutations 2871delC and R778L have been previously reported in a relatively large number of Japanese patients. In particular, R778L is known to be more prevalent in Asian countries than in other countries of the world. Our data are compatible with the hypothesis that the mutations tend to occur in a population-specific manner. Therefore, the accumulation of the types of mutations in Japanese patients with WD will facilitate the fast and effective genetic diagnosis of WD in Japanese patients.",ATP7B gene;Japanese;Mutation;Polymorphism;Wilson disease;adolescent;adult;article;case report;DNA sequence;gene;gene mutation;human;Japan;liver biopsy;liver failure/th [Therapy];male;nucleotide sequence;polymerase chain reaction;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];amino acid/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;DNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];protein/ec [Endogenous Compound];trientine/dt [Drug Therapy],"Kusuda, Y.;Hamaguchi, K.;Mori, T.;Shin, R.;Seike, M.;Sakata, T.",2000,,,0,0,
2386,Biological regulation of copper and selective removal of copper: Therapy for Wilson disease and its molecular mechanism. [Japanese],"Copper (Cu) is an essential trace element and constitutes the active center of the redox Cu enzymes such as Cu, Zn-superoxide dismutase (Cu, Zn-SOD), ceruloplasmin and cytochrome c oxidase. Among hereditary diseases due to a defect in the metabolism of Cu, Menkes disease (caused by a Cu deficiency) and Wilson disease (caused by-the excessive accumulation of Cu) have been shown to be caused by the mutation of genes encoding Cu-binding ATPase for the efflux of Cu, ATP7A and ATP7B, respectively. Following the identification of these causative genes, intracellular Cu transporters (Cu chaperones) specific for the Golgi apparatus, mitochondria and Cu, Zn-SOD were discovered, and these findings have facilitated the study of the underlying mechanisms of the biological regulation of Cu. Apart from these physiological and biochemical studies, toxicological studies have elucidated the underlying mechanisms of the occurrence of acute hepatitis caused by the accumulation of Cu accumulating in the liver of an animal model for Wilson disease, LEC rats. In these toxicological studies, two biological aspects of metallothionein (MT), i.e., antioxidant and prooxidant depending on the Cu/Zn ratio in Cu-containing MT have been proposed. The present article overviews the recent findings on the biological regulation of Cu and on the toxicological aspect of Cu. It is known that Cu forms a stable ternary complex with molybdenum and sulfur under reductive conditions in the body. On the basis of this observation, tetrathiomolybdate (TTM) has been applied to remove Cu from the liver of Long-Evans rats with a cinnamon-like coat color (LEC) rats. Precise mechanisms underlying the complex formation between Cu bound to MT and TTM were presented, and an appropriate protocol for the chelation therapy was also proposed together with the mechanisms underlying the occurrence of side-effects.",Copper;Hepatitis;LEC rat;Metallothionein;Tetrathiomolybdate;Wilson disease;animal experiment;animal model;chelation therapy;complex formation;controlled study;copper metabolism;drug effect;enzyme active site;nonhuman;review;structure analysis;Wilson disease/dt [Drug Therapy];ceruloplasmin;copper/to [Drug Toxicity];cytochrome c oxidase;superoxide dismutase;tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology],"Suzuki, K. T.;Ogura, Y.",2000,,,0,0,
2387,Early detection of non-compliance in Wilson's disease by consecutive copper determination in cerebrospinal fluid,,ataxia;attention deficit disorder;cerebrospinal fluid analysis;cerebrospinal fluid level;copper blood level;copper metabolism;diet restriction;diplopia;dysarthria;evaluation and follow up;human;letter;patient compliance;priority journal;treatment outcome;visual disorder;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Stuerenburg, H. J.;Eggers, C.",2000,,http://dx.doi.org/10.1136/jnnp.69.5.701,0,0,
2388,Wilson disease: Diagnostic dilemmas? [1],,adolescent;aminotransferase blood level;child;clinical article;copper metabolism;diagnostic accuracy;diagnostic value;female;hepatomegaly/di [Diagnosis];hepatomegaly/et [Etiology];human;letter;liver level;male;priority journal;urinary excretion;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine,"Iorio, R.;Porzio, S.;Mazzarella, G.;Fusco, G.;Vegnente, A.",2000,,,0,0,
2389,Interaction between copper and zinc at GABA(A) receptors in acutely isolated cerebellar Purkinje cells of the rat,"1. Nanomolar concentrations of Cu<sup>2+</sup> induce a slowly reversible block of GABA(A) receptor-mediated currents which can be removed by chelating substances. 2. The possible interaction of Cu<sup>2+</sup> with the Zn<sup>2+</sup> binding site on the GABA(A) receptor complex was studied in acutely isolated Purkinje cells using whole-cell recording and a fast drug application system. 3. When Zn<sup>2+</sup> was applied together with 2 muM GABA, the Zn<sup>2+</sup>-induced block of GABA-mediated currents was not additive to the Cu<sup>2+</sup>-induced block. In the presence of 0.1 muM Cu<sup>2+</sup> in the bath solution the degree of inhibition of GABA-mediated responses by Zn<sup>2+</sup> was strongly attenuated. 4. Preapplication of 100 muM Zn<sup>2+</sup> during 10 s, terminated 1 s before exposure to 2 muM GABA did not affect the GABA current in Cu<sup>2+</sup>-free solution, but relieved its block by 0.1 muM Cu<sup>2+</sup>. This effect of Zn<sup>2+</sup> was concentration-dependent with an EC<inf>50</inf> of 72 muM. 5. When the Cu<sup>2+</sup>-induced block was removed by histidine, preapplication of Zn<sup>2+</sup> did not increase the GABA current, indicating that the relief of Cu<sup>2+</sup> block by Zn<sup>2+</sup> is the result of its ability to actively remove Cu<sup>2+</sup> from the GABA receptor complex. 6. It is proposed that the inhibitory effects of Zn<sup>2+</sup> and Cu<sup>2+</sup> on GABA-induced currents result from an action of these metal ions at distinct, but conformationally linked sites on the GABA(A) receptor protein. Under physiological conditions Zn<sup>2+</sup> would liberate Cu<sup>2+</sup> from the GABA(A) receptor, thus facilitating Cu<sup>2+</sup> turnover and its binding by other endogenous chelating molecules.",Cerebellum;Cu<sup>2+</sup>;gaba;Histidine;Patch-clamp;Wilson disease;Zn<sup>2+</sup>;animal cell;article;concentration response;controlled study;male;nonhuman;patch clamp;priority journal;Purkinje cell;rat;Wilson disease/et [Etiology];4 aminobutyric acid;4 aminobutyric acid A receptor/ec [Endogenous Compound];copper ion/ec [Endogenous Compound];zinc ion/ec [Endogenous Compound],"Sharonova, I. N.;Vorobjev, V. S.;Haas, H. L.",2000,,,0,0,
2390,Metabolic fate of the insoluble copper/tetrathiomolybdate complex formed in the liver of LEC rats with excess tetrathiomolybdate,"Copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease, can be removed from the MT with tetrathiomolybdate (TTM). However, the insoluble Cu/TTM complex formed with excess TTM is known to be deposited in the liver. The metabolic fate of the insoluble Cu/TTM complex was investigated in the present study. LEC rats were injected with TTM at the dose of 10 mg/kg body weight for 8 consecutive days and were fed with a standard or low Cu diet for 14 days after the last injection. About 95% of the Cu in the liver became insoluble together with Mo. The concentration of Cu in the liver supernatants of rats fed with the standard diet increased significantly compared with that in rats dissected 24 h after the last injection (control rats), while the concentration in rats fed with the low Cu diet remained at a comparable level to that in the controls. The rate of Cu accumulation in the livers of rats fed with the standard diet did not differ before and after the treatment, suggesting that there was no rebound effect by treatment with TTM. These results suggest that the insoluble Cu/TTM complex is resolubilized in the liver, and that the solubilized complex is excreted into the bile and blood, i.e., the insoluble Cu/TTM complex is not the source of Cu re-accumulation in the form bound to MT in the liver after TTM treatment. It was concluded that, once Cu is complexed with TTM, the metal is excreted either immediately in the soluble form or slowly in the insoluble form into the bile and blood. Copyright (C) 2000 Elsevier Science Inc.",Copper;Inductively coupled argon plasma-mass spectrometry;LEC rat;Tetrathiomolybdate;Wilson disease;animal model;animal tissue;argon plasma coagulation;article;biliary excretion;blood;complex formation;controlled study;diet;liver;male;mass spectrometry;metabolism;nonhuman;rat;solubilization;supernatant;Wilson disease/et [Etiology];copper/to [Drug Toxicity];copper complex;metallothionein/ec [Endogenous Compound];molybdenum;tetrathiomolybdic acid/cr [Drug Concentration];tetrathiomolybdic acid/ip [Intraperitoneal Drug Administration];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology],"Ogra, Y.;Chikusa, H.;Suzuki, K. T.",2000,30 Jan,http://dx.doi.org/10.1016/S0162-0134%2899%2900218-4,0,0,
2391,DNA haplotype analysis for the diagnosis of Wilson disease in siblings,,adolescent;article;autosomal recessive disorder/di [Diagnosis];child;chromosome 13;clinical article;clinical feature;controlled study;copper metabolism;differential diagnosis;female;gene mutation;genetic analysis;genetic linkage;genetic screening;haplotype;heterozygosity;human;male;ophthalmology;priority journal;protein blood level;sibling;urine level;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];DNA/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Yuce, A.;Kocak, N.;Demirtas, M.;Ozen, H.;Gurakan, F.;Ozguc, M.",2000,,,0,0,
2392,"Transplant livers in Wilson's disease for hepatic, not neurologic, indications (mulitiple letters)",,brain injury/di [Diagnosis];brain injury/et [Etiology];brain injury/th [Therapy];copper blood level;letter;liver failure/su [Surgery];liver transplantation;morbidity;mortality;neurologic disease/co [Complication];neurologic disease/pc [Prevention];priority journal;prognosis;treatment indication;Wilson disease/su [Surgery];copper/to [Drug Toxicity];penicillamine,"Brewer, G. J.;Askari, F.;Eghtesad, B.;Fung, J. J.;Rakela, J.",2000,,,0,0,
2393,Linear focal elastosis,"Three patients with linear focal elastosis are described; all were male, and aged 17, 18, and 19 years old, respectively. The lesions were located across the middle and lower parts of the back in two patients; the third one presented lesions similar to the other two, simulating atrophic striae, on the middle back, dorsal area of the upper arms, and a few lesions on the scapular region. The histopathology was characterized by 'wavy bundles of elastic fibers' mainly on the middle and lower dermis.",Elastic tissue;adult;article;case report;clinical feature;cryotherapy;drug induced disease/di [Diagnosis];drug induced disease/dt [Drug Therapy];drug induced disease/et [Etiology];drug induced disease/si [Side Effect];drug induced disease/th [Therapy];elastic fiber;elastosis/di [Diagnosis];elastosis/dt [Drug Therapy];elastosis/et [Etiology];elastosis/si [Side Effect];elastosis/th [Therapy];electrocoagulation;electron microscopy;hepatic encephalopathy;histopathology;human;human tissue;hyperkeratosis;jaundice;male;skin biopsy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];collagen fiber/ec [Endogenous Compound];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];retinoic acid/dt [Drug Therapy];retinoic acid/tp [Topical Drug Administration];zinc acetate/dt [Drug Therapy],"Helder Cavalcante, F.;Talhari, S.;De Lima Ferreira, L. C.;De Andrade, R. V.",2000,,,0,0,
2394,Localized idiopathic elastosis perforans serpiginosa effectively treated by the Coherent Ultrapulse 5000C Aesthetic Laser,,cryotherapy;cystinuria/dt [Drug Therapy];dermis;elastic fiber;elastic tissue;elastosis/dt [Drug Therapy];elastosis/et [Etiology];elastosis/si [Side Effect];elastosis/su [Surgery];elastosis/th [Therapy];human;idiopathic disease;laser surgery;letter;pain/co [Complication];papule;skin biopsy;Wilson disease/dt [Drug Therapy];carbon dioxide/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];corticosteroid/il [Intralesional Drug Administration];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Abdullah, A.;Colloby, P. S.;Foulds, I. S.;Whitcroft, I.;Franco, R. C.",2000,,http://dx.doi.org/10.1046/j.1365-4362.2000.00036-2.x,0,0,
2395,Minimal diagnostic criteria and theray in Wilson's desease: The point of view of the pedriatric hepatologist. [Italian],,clinical feature;conference paper;copper blood level;human;prognosis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];zinc acetate/dt [Drug Therapy];zinc acetate/po [Oral Drug Administration];zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration],"Iorio, R.",2000,,,0,0,
2396,A new variant deletion of a copper-transporting P-type ATPase gene found in patients with Wilson's disease presenting with fulminant hepatic failure,"A candidate gene (ATP7B) for Wilson's disease, an autosomal recessive disorder of copper transport, has recently been identified. We examined the ATP7B gene in two Japanese sisters with Wilson's disease presenting with fulminant hepatic failure but who did not exhibit Kayser-Fleischer rings or abnormal neurological findings. Genomic DNA was isolated from the whole blood of the patients and their family. Entire exons of ATP7B, and their associated splice junctions, were amplified by polymerase chain reaction. The sequencing of all exons was performed by a non-radioactive sequencing method. The sequencing of exon 12 of ATP7B revealed a 9-bp deletion. The mutation deleted 922Gly, 923Tyr, and 924Phe, and three residues conserved in the Menkes gene, ATP7A, located in the fifth transmembrane region. Of the 14 family members tested, 7 were normal and 7 were heterozygous for the deletion. Mean serum copper and cerulopasmin levels were significantly lower in the family members who were heterozygous for the deletion than in the normal family members, and two heterozygous family members showed abnormally low cerulopasmin levels; however, there were no differences in mean aspartate aminotransferase or alanine aminotransferase levels between the two groups.",Hepatolenticular degeneration;Mutation of ATP7B gene;adolescent;alanine aminotransferase blood level;article;aspartate aminotransferase blood level;autopsy;case report;ceruloplasmin blood level;clinical feature;copper blood level;exon;female;gene amplification;gene deletion;gene isolation;gene location;gene sequence;heterozygote;human;human tissue;liver biopsy;liver failure;pedigree;plasmapheresis;polymerase chain reaction;priority journal;sibling;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];adenosine triphosphatase/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Okada, T.;Morise, T.;Takeda, Y.;Mabuchi, H.",2000,April,,0,0,
2397,'Face of the giant panda' sign in Wilson's disease: Revisited,"We report a patient, with Wilson's disease, who showed the characteristic radiological sign known as 'Face of the giant panda sign' on magnetic resonance imaging (MRI) of the brain.",Basal ganglia;Magnetic resonance imaging;Wilson's disease;adult;article;basal ganglion;case report;clinical feature;female;follow up;human;nuclear magnetic resonance imaging;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration],"Kuruvilla, A.;Joseph, S.",2000,,,0,0,
2398,Dissolution of copper-rich granules in hepatic lysosomes by D- penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon rats,"Background/Aim: The Long-Evans cinnamon rat has a mutation homologous to the human Wilson disease gene, leading to gross copper accumulation and the development of hepatitis. D-penicillamine, a copper-chelating drug widely and efficiently used in treating Wilson disease, has also been shown to prevent hepatitis in Long-Evans cinnamon rats. The objectives of this study were: i) to investigate the effectiveness of D-penicillamine when administered to the already affected animals, and ii) to elucidate the mechanism of action of the drug. Methods: Long-Evans cinnamon rats were divided into groups according to age and treatment with D-penicillamine. The drug was administered orally before and after the onset of hepatitis. Livers were examined by light and electron microscopy. The effect of D-penicillamine on the subcellular distribution and binding of copper was investigated in more detail. Finally, the interaction between D-penicillamine and specific hepatic copper-binding proteins was studied in vitro. Results: D-penicillamine when given to either healthy or diseased animals prevented or reversed hepatitis, respectively. The drug particularly inhibited the disease specific accumulation of copper in lysosomes of hepatocytes, tissue macrophages and Kupffer cells. When administered to diseased animals, the drug sequestered copper particularly from insoluble lysosomal particles. According to results obtained in vitro, the mobilization of this copper is likely to proceed through the solubilization of these particles. In contrast and as supported by the in vitro data, D-penicillamine had only a minor effect on copper bound to metallothionein in the cytosol. Conclusion: Our findings on the Long-Evans cinnamon rat provide some conclusions on the mechanism of action of D- penicillamine in Wilson disease therapy. The drug prevents the formation or promotes the solubilization of copper-rich particles which occur in lysosomes of hepatocytes and Kupffer cells in the livers of patients with Wilson disease. Once chelated with D-penicillamine copper might then be excreted into urine. However, the mobilization of copper by D-penicillamine seems to be limited due to the binding of the metal to metallothionein in liver cytosol. This copper, even at relatively high concentrations, apparently may be well tolerated.",Copper toxicity;D-penicillamine;Hepatitis;LEC rat;Lysosomes;Metallothionein;Wilson disease;animal experiment;animal model;animal tissue;article;chelation;controlled study;copper metabolism;drug effect;drug efficacy;female;hepatitis/dt [Drug Therapy];hepatitis/pc [Prevention];Kupffer cell;liver;liver lysosome;macrophage;male;nonhuman;priority journal;rat;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration],"Klein, D.;Lichtmannegger, J.;Heinzmann, U.;Summer, K. H.",2000,February,,0,0,
2399,CopA: An Escherichia coli Cu(I)-translocating P-type ATPase,"The copA gene product, a putative copper-translocating P-type ATPase, has been shown to be involved in copper resistance in Escherichia coli. The copA gene was disrupted by insertion of a kanamycin gene through homologous recombination. The mutant strain was more sensitive to copper salts but not to salts of other metals, suggesting a role in copper homeostasis. The copper-sensitive phenotype could be rescued by complementation by a plasmid carrying copA from E. coli or copB from Enterococcus hirae. Expression of copA was induced by salts of copper or silver but not zinc or cobalt. Everted membrane vesicles from cells expressing copA exhibited ATP-coupled accumulation of copper, presumably as Cu(I). The results indicate that CopA is a Cu(I)-translocating efflux pump that is similar to the copper pumps related to Menkes and Wilson diseases and provides a useful prokaryotic model for these human diseases.",Menkes;Soft metal resistance;Wilson disease;article;Enterococcus hirae;enzyme activity;Escherichia coli;gene translocation;homeostasis;phenotype;polyacrylamide gel electrophoresis;polymerase chain reaction;priority journal;prokaryote;adenosine triphosphatase;carrier protein;copper,"Rensing, C.;Fan, B.;Sharma, R.;Mitra, B.;Rosen, B. P.",2000,18 Jan,http://dx.doi.org/10.1073/pnas.97.2.652,0,0,
2400,Excretion of copper complexed with thiomolybdate into the bile and blood in LEC rats,"Copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease, was removed with ammonium tetrathiomolybdate (TTM), and the fate of the Cu complexed with TTM and mobilized from the liver was determined. TTM was injected intravenously as a single dose of 2, 10 or 50 mg TTM/kg body weight into LEC and Wistar (normal Cu metabolism) rats, and then the concentrations of Cu and molybdenum (Mo) in the bile and plasma were monitored with time after the injection. In Wistar rats, most of the Mo was excreted into the urine, only a small quantity being excreted into the bile, while Cu excreted into the urine decreased. However, in LEC rats, Cu and Mo were excreted into the bile and blood, and the bile is recognized for the first time as the major route of excretion. The Cu excreted into both the bile and plasma was accompanied by an equimolar amount of Mo. The relative ratio of the amounts of Cu excreted into the bile and plasma was 40/60 for the low and high dose groups, and 70/30 for the medium dose group. The systemic dispositions of the Cu mobilized from the liver and the Mo complexed with the Cu were also determined for the kidneys, spleen and brain together with their urinal excretion. Although Mo in the three organs and Cu in the kidneys and spleen were increased or showed a tendency to increase, Cu in the brain was not increased at all doses of TTM. Copyright (C) 2000 Elsevier Science Ireland Ltd.",Chelation therapy;Copper;LEC rat;Metallothionein;Tetrathiomolybdate;Wilson disease;animal model;animal tissue;article;bile flow;blood analysis;controlled study;nonhuman;protein binding;rat;urinary excretion;copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper complex;metallothionein/ec [Endogenous Compound];thiomolybdic acid,"Komatsu, Y.;Sadakata, I.;Ogra, Y.;Suzuki, K. T.",2000,01 Feb,http://dx.doi.org/10.1016/S0009-2797%2899%2900159-3,0,0,
2401,Hemochromatosis and Wilson's disease. [German],,hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/et [Etiology];human;pathogenesis;prognosis;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Herrmann, T.;Smolarek, C.;Gehrke, S.;Schafer, M.;Stremmel, W.",1999,,http://dx.doi.org/10.1007/s001080050365,0,0,
2402,"Pregnancy, labor and early puerperium in a patient with Wilson's disease. [Slovak]","Pregnancy should have a successful outcome in a patient with treated Wilson's disease if complications are excluded before conception. Chelating treatment must be maintained, although there is some concern about its teratogenicity. We describe the course of pregnancy in a patient with Wilson's disease treated with D-penicillamine and zinc sulfate.",adult;article;case report;chemically induced disorder;female;foot malformation;human;newborn;pregnancy;pregnancy complication/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy],"Hlinst'ak, K.;Borovsky, M.;Hlinst'akova, S.",1999,Jun,,0,0,
2403,Therapy of Wilson disease. [German],"Wilson disease is a copper storage disease with autosomal-recessive trait that is predominantly a disorder of the adolescent and young adult. Clinical manifestations are dominated by hepatic and/or neurological symptoms. Diagnostic procedures include determination of total serum copper, free serum copper and serum ceruloplamin concentrations as well as urinary copper excretion. Confirmation of diagnosis may be achieved by liver biopsy and histological determination of copper content. The aim of treatment is reduction of tissue copper concentration and detoxification of copper. Drugs applied are the chelating agents. D-penicillamine and trientine, or zinc. The chelating agents induce renal and biliary copper excretion and increased synthesis of metallothionein, which attaches and detoxifies intracellular copper, leading to impaired absorption and binding of excess intracellular copper. Treatment with zinc results in induction of hepatic and intestinal metallothionein synthesis. Regular examinations of the parameters of copper metabolism are necessary in order to control the therapeutic effect. Free copper serum concentrations and urinary copper excretion should reach values below 10 micrograms/dl and 80 micrograms/day, respectively. A significant improvement of clinical symptoms and normalization of parameters of copper metabolism can be expected earliest six months after onset of therapy. Anti-copper treatment may be accompanied by copper-reduced diet. Lifelong therapy is required and provides life-expectancy near to normal. Interruption of treatment leads to reaccumulation of copper, often resulting in fulminant hepatic failure. This can also be observed as initial presentation in 5% of cases (predominant age 12 to 25 years). End stage liver disease and fulminant hepatic failure are indications for liver transplantation by which the genetic defect is phenotypically cured. Here decoppering treatment is no longer required. Whether severe neurological disorders may also be improved is not clear until today.",adolescent;adult;blood;child;female;genetics;human;liver transplantation;male;metabolism;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Smolarek, C.;Stremmel, W.",1999,Apr,,0,0,
2404,Copper and selenium plasma concentrations in patients with Wilson's disease treated with zinc. [Czech],"Zinc administered on a long-term basis in excess to patients with Wilson's disease blocks in a significant way copper absorption from the gut, prevents its accumulation and toxic action in the organism. The authors investigated the effect of its long-term administration on the plasma concentration of copper, zinc and selenium, on the superoxide dismutase activity in red blood cells and glutathione peroxidase activity in whole blood. In seven patients with Wilson disease treated with zinc sulphate, 136 mg of elemental zinc for 1.5 years (18 months), the authors assessed the plasma concentration of zinc, copper, selenium and ceruloplasmin, the activity of superoxide dismutase in red blood cells, the activity of glutathione peroxidase in whole blood and the urinary excretion of zinc and copper in 24 hours. Envisaged findings with regard to the diagnosis of the investigated patients and their treatment: elevated plasma zinc concentration and increased urinary excretion, reduced copper and ceruloplasmin plasma concentration and increased urinary copper excretion. The authors recorded also a significantly higher concentration of superoxide dismutase in red blood cells (p < 0.05). The increase of the glutathione peroxidase activity in whole blood in the investigated patients was not significant (p < 0.05).",Copper;Glutathione peroxidase;Selenium;Superoxide dismutase;Treatment;Wilson's disease;Zinc;adult;article;clinical article;copper blood level;copper metabolism;drug effect;enzyme activity;erythrocyte;female;glutathione metabolism;human;intestine absorption;long term care;male;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc blood level;copper/ec [Endogenous Compound];glutathione peroxidase/ec [Endogenous Compound];selenium/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Dastych, M.",1999,,,0,0,
2405,Acute haemolytic anemia associated with D-penicillamine absorption deficiency in Wilson's disease [1]. [Spanish],,adult;clinical feature;diagnostic procedure;disease association;drug metabolism;hemolytic anemia/co [Complication];human;intestine absorption;letter;male;oral drug administration;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ramirez Sanchez, M. J.;Calvo Villas, J. M.;Sicilia Guillen, F. J.;Salah, S.",1999,,,0,0,
2406,Wilson disease. [Japanese],,classification;differential diagnosis;genetics;human;prognosis;review;urine;Wilson disease/di [Diagnosis];adenosine triphosphatase;adenosine triphosphate;biological marker/an [Drug Analysis];ceruloplasmin/an [Drug Analysis];chelating agent/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Shimizu, N.",1998,,,0,0,2191
2407,Inborn errors of trace metals. [Japanese],,disorders of metal metabolism;hemochromatosis;human;Menkes syndrome;metabolism;pathophysiology;physiology;review;Wilson disease;copper;iron;molybdenum;zinc,"Aoki, T.",1998,,,0,0,
2408,Wilson's disease ('hepatic form') in a region endemic for mansoni schistosomiasis: The clinical presentation of 25 patients. [Portuguese],"Brazil has a young population and areas of endemic mansoni schistosomiasis where Wilson's disease might be easily misdiagnosed in patients erroneously classified as having either the hepatosplenic or the hepatointestinal form of the helminthiasis. Twenty five patients with the 'hepatic form' of Wilson's disease (14 males and 11 females) were investigated in Belo Horizonte, MG; the mean age was 13,7 years (3 to 22). Nineteen had hepatomegaly (76%) and nine splenomegaly (36%). Twenty two (88%) had cirrhosis. The Kaiser-Fleisher ring was detected in fifteen (60%). Four (16%) had clear neurological abnormalities. Eleven (44%) had ascitis and/or jaundice. Ninety one point three per cent and 92% had low ceruloplasmin and copper serum levels respectively. Eighty four point two per cent showed an increased 24 hours urinary copper excretion; seven patients in whom hepatic copper was determined had increased values. Six out of nine had at least a ten fold increase in 24 hours urinary copper excretion following penicillamine use ('penicillamine test'). Three out of 19 patients (15,8%) had mansoni schistosoma ova in stools examination, a common prevalence in our population. Their biopsies showed inactive cirrhosis without schistosomiasis- associated alterations. At least fourteen patients (56%) could be misdiagnosed as having hepatointestinal or hepatosplenic schistosomiasis when in fact they suffered from Wilson's disease with or without asymptomatic intestinal schistosomiasis, losing the chance of an early treatment. The follow-up time of 22 patients was 52 months (1 to 96): eight (36,3%) died, four from bleeding esphageal varices, three from terminal hepatic failure and one from fulminant liver failure. The majority of the patients, including those who died, had abandomned the use of penicillamine or had taken it irregularly, due mainly to its highly expensive cost. A 17 year old patient underwent a successful liver transplant in 1989.",Hepatolenticular degeneration;Liver cirrhosis;Schistosomiasis mansoni;article;ascites/co [Complication];bleeding/co [Complication];Brazil;ceruloplasmin blood level;copper blood level;diagnostic error;esophagus varices/co [Complication];feces analysis;helminthiasis/et [Etiology];hepatomegaly;jaundice/co [Complication];liver cirrhosis/co [Complication];liver failure/co [Complication];Schistosoma mansoni;schistosomiasis/di [Diagnosis];schistosomiasis/et [Etiology];splenomegaly;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Galizzi-Filho, J.;Andrade, M. D. O.;Cota, M. D. M.;Penna, F. J.;Figueiredo-Filho, P. P.;Valadares, C. A. M.;Machado-Silva, R.;Barquete, J.;De Oliveira, J. P. M.;De Almeida, J. A.",1998,,,0,0,
2409,Schizophrenic-like symptoms in the Westphal-Strumpell form of Wilson's disease. [German],"Wilson's disease is a rare, autosomal recessive disorder of copper metabolism due to low serum ceruloplasm, resulting in increased copper deposition, especially in the liver and basal ganglia in the brain. The pseudosclerotic type of Wilson's disease, also known as the Westphal- Strumpell form, is distinguished by positional tremor, ataxia and dysarthria as the main symptoms. We use the example of a 23-year-old patient whose neurological symptoms were preceded by a long history of a schizophrenic- like disorder. Clinical symptoms are presented. MRI, SPECT and PET images are illustrated. Therapy and outcome are discussed.",Organic psychosis;Schizophrenic-like symptoms;Westphal- Strumpell form;Wilson's disease;adult;article;ataxia;autosomal recessive disorder/di [Diagnosis];case report;dysarthria;extrapyramidal symptom;human;liver disease/di [Diagnosis];metabolic disorder/di [Diagnosis];neurological complication;psychosis/et [Etiology];schizophrenia/et [Etiology];symptomatology;tremor;Wilson disease/di [Diagnosis];penicillamine/dt [Drug Therapy],"Muller, J.;Landgraf, F.;Wtrabert",1998,March,http://dx.doi.org/10.1007/s001150050269,0,0,
2410,Zinc treatment of Wilson's disease: Editorial,,drug approval;editorial;food and drug administration;human;pathology;United States;Wilson disease/dt [Drug Therapy];zinc/dt [Drug Therapy],"Hoogenraad, T. U.",1998,1998,,0,0,
2411,Neuroradiological findings in 2 cases of Wilson disease with neurological involvement. [Spanish],"Wilson disease is an inborn error of copper metabolism that has neurological and hepatic manifestations. We report a 13 years old girl and a 12 years old boy with Wilson disease. In both patient, brain computed tomography and magnetic resonance imaging showed marked involvement of basal ganglia and other deep gray nuclei. Considering that this is a treatable disease, it should be included in the differential diagnosis of the so called ""striatal necrosis of childhood"".",adolescent;article;case report;child;computer assisted tomography;female;human;male;neurologic disease/et [Etiology];Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];vitamin K group/dt [Drug Therapy],"Troncoso, M.;Badilla, L.;Bravo, E.;Miranda, M.;Gajewski, C.;Barrios, A.;Villagra, R.",1998,Jan,,0,0,
2412,Wilson's disease and pregnancy. [German],"Wilson's disease is an autosomal recessive disorder of copper metabolism. Since the introduction of penicillamine treatment successful pregnancies have been reported. However little is known about the risks of breast feeding in patients on this medication. We describe the case of a patient suffering from Wilson's disease, who had two uncomplicated pregnancies and breast fed both children for a period of three months each. In the 22 year old gravida I para I the diagnosis of Wilson's disease had been previously made by liver biopsy and penicillamin therapy had been begun. At the time of her first presentation at our department she was 8 weeks pregnant. Her renal and liver function were normal. Neurologic or psychiatric symptoms were not observed. At 18 weeks the dosage of penicillamin was reduced from 900 mg/d to 750 mg/d. The course of the pregnancy remained uneventful. At 38 + 1 weeks a healthy boy of 3100 gm was delivered. 19 months later the patient presented again in the 16th week of her second pregnancy. Concerning Wilson's disease no major changes were observed, especially liver and renal function were not impaired. The dosage of penicillamin was reduced from 900 mg/d to 750 mg/d during the 21st week. The pregnancy again was uncomplicated and at 38 + 2 weeks resulted in the spontaneous delivery of a healthy boy, weighing 3940 gm. Both children were breast fed over a period of three months and with the exception of an icterus prolongatus no adverse effects were noted.",D-Penicillamin;Prolonged icterus;Wilson's disease;adult;article;autosomal recessive disorder/cn [Congenital Disorder];breast feeding;case report;copper metabolism;female;human;jaundice/co [Complication];liver biopsy;pregnancy;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Messner, U.;Gunter, H. H.;Niesert, St",1998,,,0,0,
2413,Treatment of chronic Wilson's disease in 2 patients using plasmapheresis--clinico-biochemical observations. [Croatian],"INTRODUCTION: The introduction of penicillamine in the treatment of Wilson's disease (hepatolenticular degeneration) was a historical event [1]. D-pericillamine (d-PAM) showed some potential side effects such as myasthenia, kidney toxicity, etc. In previous decade the treatment of Wilson's disease (WD) with zinc sulphate started successfully [4]. Danks [7] described the use of exchanged transfusions, peritoneal dialysis and plasmapheresis in the treatment of young patients with WD in acute liver failure. These patients had acute copper poisoning. The results of this study were beneficial. MATERIAL AND METHODS: Therapeutic plasmapheresis (PF) has been used in many diseases in which immunological mechanisms are proved [8, 9]. We started with using PF in the treatment of two young chronic patients with Wilson's disease. The clinical picture of patients became worse, probably due to the decrease in cupriuretic effect of d-PAM. One patient (1) did not take d-PAM regularly. In this study PF was performed with the use of haemonetics V-50 and filter 704. During the treatment with PF, 2000 ml of plasma was always exchanged, i.e. removed. During the treatment with PF the patients were hospitalized at the Department of Neurology and Psychiatry of Children and Young People. CASE REPORT AND RESULTS: Patient No. 1. A 24-year-old man, born in 1965, came with a coarse tremor. He has been diagnosed as WD at the age of 18. Kayser-Fleischer rings were found in the cornea by slit-lamp examination. The disease began when he was 15 years old with polymorphous difficulties. In time tremor became more severe. It was apparent when the patient made any movement. The first treatment with PF (1) lasted from February 13 to March 16, 1989. The patient had 10 PF without any side effect. During the treatment with PF the patient felt better. After PF-tremor was reduced significantly, and subjective and objective condition ameliorated. The patient (1) was readmitted to the hospital on June 24, 1991 for continuation of the treatment with PF. Anamnestic data and neurological examination revealed progression of the disease. His condition became worse, especially tremor. He could not write a single letter (Figures 1-5) and walk without help of the others. His tremor became the severest when he made any kind of voluntary movement. The second treatment with PF started on June 25, 1991 and finished on July 16, 1991. He received 9 PF in this series. The treatment was without side effects. Tremor was reduced approximately by 15%. Plasma copper examined before and after 9 PF showed different values (Table 2). This difference (2.79 mumol/l; 23.70%) in plasma copper level was removed from circulation. Patient No. 2. A 23-year-old man, born in 1966, came to the hospital with acute exacerbation of WD. At the age of 16 latent psychosis was diagnosed. One year later diagnosis of WD was established in the hospital when he was 17 years old. Kayser-Fleischer rings were found in the cornea by slit-lamp examination. The treatment with d-PAM and other drugs (BAL, symptomatic therapies, sedatives, antidepressants, etc.) has been accompanied with good and long-term remissions and short exacerbation. A few years later exacerbation became longer and longer and worse and worse. He was admitted to the hospital on November 28, 1989 with acute relapse of WD. His condition was very difficult, completely bedridden. The treatment with PF started on December 26, 1989 and lasted to January 25, 1990. The treatment with PF was without d-PAM. He was only given symptomatic therapies. After a few PF he demonstrated side effects with nausea, sometimes vomiting, face sweating, pulse rate of about 120/min while blood pressure was normal. Therefore he was given human albumin in the next day, and no side effects were observed. The removal of little plasma copper from blood circulation correlated well with a small improvement in clinical symtpomatology. The rigidity was reduced and voluntary movements bec",adult;article;blood;case report;chronic disease;human;male;plasmapheresis;Wilson disease/th [Therapy];chelating agent/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Milovanovic, D. D.;Tomasevic, R.;Bogdanovic, G.",1998,1998,,0,0,
2414,Ocular manifestation in M. Wilson. [German],,cataract;clinical feature;eye disease/di [Diagnosis];human;liver transplantation;review;Wilson disease/di [Diagnosis];penicillamine;trientine;zinc,"Becker, M.;Rohrschneider, K.",1997,November,http://dx.doi.org/10.1007/s003470050213,0,0,
2415,Contrast analysis of brainstem auditory evoked potential in untreated and treated hepatolenticular degeneration patients with treatment of combining traditional Chinese and Western medicine. [Chinese],"OBJECTIVE: To observe the effect of combination therapy of traditional and Western medicine (TCM-WM) on brainstem auditory evoked potential (BAEP) in hepatolenticular degeneration patients. METHODS: BAEP was recorded and analyzed in 65 patients with hepatolenticular degeneration (HLD) before and after decoppered TCM-WM treatment. RESULTS: The peak latency (PL) and interpeak latency (IPL) of BAEP in untreated patients were greatly increased compared with those of control group, especially in the prolongations of III, V, III- V and I-V. The PL and IPL improved as improvement of clinical symptoms in HLD patients treated with TCM-WM than that in untreated patients. The abnormal rates of men and women in BAEP were decreased from 21.97% and 19.05% in untreated patients to 9.09% and 6.75% in treated patients respectively. CONCLUSION: BAEP not only has an complementary diagnosis but also judge the efficacy of treatment on the HLD disease.",adolescent;adult;article;child;comparative study;drug effect;evoked brain stem auditory response;female;human;male;pathophysiology;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];herbaceous agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];succimer/dt [Drug Therapy],"Xu, S. H.;Cai, Y. L.;Yang, R. M.",1997,Jan,,0,0,
2416,"A late form of Wilson's disease, with psychiatric first aspect and pseudo-compulsive stereotypies neuroradiological correlations. [French]","Wilsons disease rarely starts after the third decade and may present with misleading psychiatric sipns. We observed a 39-year-old white male who developed hysterical behaviour followed by frank delusional psychosis. Secondary neurological symptoms like astasia and dysarthria were misinterpreted as drug-induced. Despite a treatment with D-penicillamine and zinc sulfate there was further deterioration with anarthria and pseudo-compulsive stereotypies. These latter signs cleared after five months, whereas astasia and abasia remained the same and MRI imaging showed further deterioration characterized by marked bilateral putaminal cavitation. SPECT imaging could not predict the clinical evolution. Our case emphasizes that Wilson's disease can have variable initial presentations, and confirms the relationship between pseudo-compulsive stereotypies and bilateral lenticular lesions, as already described in other diseases of the basal ganglia.",adult;article;case report;dysarthria;human;hysteria;male;neuroradiology;nuclear magnetic resonance imaging;psychosis;single photon emission computer tomography;stereotypy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Garnier, H.;Diederich, N.;Pilloy, W.;Lenaerts, M.;Dooms, G.;Metz, H.",1997,March,,0,0,
2417,Chronic internuclear ophthalmoplegi: A manifestation of D-penicillamine cerebral vasculitis,,Cerebral vasculitis;D-penicillamine;Eye movements;Internuclear ophthalmoplegia;adult;article;brain vasculitis/di [Diagnosis];brain vasculitis/dt [Drug Therapy];brain vasculitis/si [Side Effect];case report;clinical feature;diplopia/si [Side Effect];female;headache/si [Side Effect];human;internuclear ophthalmoplegia/di [Diagnosis];internuclear ophthalmoplegia/si [Side Effect];nausea/si [Side Effect];priority journal;tinnitus/si [Side Effect];Wilson disease/dt [Drug Therapy];cyclophosphamide/dt [Drug Therapy];methylprednisolone;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Pless, M.;Sandson, T.",1997,March,,0,0,
2418,28-year-old man with renal insufficiency and Jaundice,,adult;article;autosomal recessive disorder/di [Diagnosis];autosomal recessive disorder/dt [Drug Therapy];autosomal recessive disorder/et [Etiology];autosomal recessive disorder/su [Surgery];case report;clinical feature;diagnostic test;human;jaundice;kidney failure;liver cirrhosis;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/su [Surgery];liver failure;liver function test;liver transplantation;male;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine;zinc,"Lazaridis, K. N.;Kamath, P. S.",1997,,,0,0,
2419,Progress on diagnosis and therapy of water-electrolyte balance--disorders of trace element metabolism. [Japanese],,acrodermatitis/et [Etiology];aging;human;immunological tolerance;Menkes syndrome/et [Etiology];metabolism;review;Wilson disease/et [Etiology];copper;free radical;peroxide;trace element;zinc,"Wada, O.;Yanagisawa, H.;Nodera, M.",1997,10 Oct,,0,0,
2420,"Haemochromatosis, Wilson's disease. Illnesses which should be evoked more often. [French]",,hemochromatosis/co [Complication];human;short survey;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Valla, D.",1996,,,0,0,
2421,Reversible Magnetic Resonance Imaging Lesions in Wilson's Disease: Clinical-Anatomical Correlation,"Described herein is a patient with Wilson's disease who had tremor as a prominent neurological manifestation. T2-weighted magnetic resonance imaging showed abnormal high signal intensities in the bilateral lenticular nuclei, thalami, and red nuclei of the midbrain. Improvement of tremor with copper chelating agents was well correlated with a decrease of the abnormal signals in the thalami and the red nuclei. Copyright © 1996 by the American Society of Neuroimaging.",academic achievement;acceleration;ADL disability;adolescent;article;ataxic gait;brain nucleus;brain third ventricle;brain ventricle dilatation/di [Diagnosis];case report;copper blood level;drug dose increase;drug substitution;drug withdrawal;dysarthria;dysphagia;dystonia;female;granulocytopenia/si [Side Effect];human;lenticular nucleus;mental instability;mesencephalon;neuroanatomy;neurologic examination;nuclear magnetic resonance imaging;personality disorder;red nucleus;thalamus;tremor/dt [Drug Therapy];urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];clonazepam/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tiapride/dt [Drug Therapy];trientine/dt [Drug Therapy],"Takahashi, W.;Yoshii, F.;Shinohara, Y.",1996,,http://dx.doi.org/10.1111/jon199664246,0,0,
2422,"The effect of subcutaneous tetrathiomolybdate administration on copper and iron metabolism, including their regional redistribution in the brain, in the Long-Evans Cinnamon rat, a bona fide animal model for Wilson's disease","The present work was performed to examine the effect of tetrathiomolybdate on Cu and Fe metabolism, especially redistribution of Cu and Fe in the brains of Long-Evans Cinnamon rats, with inherently abnormal Cu deposition in the liver. The drug was injected subcutaneously at 5 mg/kg of body weight twice a week for 65 days (total dose of 20 mg) into 40-day-old Long-Evans Cinnamon rats. In Long-Evans Cinnamon rats treated with tetrathiomolybdate, the hepatic Cu concentration was 60 mug/g wet weight, compared to 170 mug/g in untreated rats. In seven brain regions (cerebellum, medulla oblongata, hypothalamus, striatum, midbrain, hippocampus and cortex) of the Long-Evans Cinnamon rats treated with tetrathiomolybdate, the Cu concentration (1.5 to 2.3 mug/g) was slightly lower (1.6 to 2.7 mug/g) than in untreated rats. A significant difference between the two groups was found only in the midbrain. Brain Fe concentrations in regions other than the striatum were not changed significantly by the tetrathiomolybdate injections. The hepatic Fe concentration was about 120 mug/g in Long-Evans Cinnamon rats without tetrathiomolybdate. Tetrathiomolybdate injection further increased the concentration to about 250 mug/g. Our results indicated that subcutaneous tetrathiomolybdate injection did not have an effect that stimulated redistribution of Cu and Fe in the seven brain regions examined, although hepatic Cu was markedly decreased and the removed Cu was deposited in kidneys, spleen and testes. The increased hepatic Fe level should be taken into account when considering side effects of the compound.",animal experiment;animal model;animal tissue;article;brain cortex;brain level;brain region;cerebellum;controlled study;copper metabolism;corpus striatum;drug effect;hippocampus;hypothalamus;iron metabolism;liver level;male;medulla oblongata;mesencephalon;nonhuman;oral drug administration;priority journal;rat;subcutaneous drug administration;tissue distribution;Wilson disease;alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];copper/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];tetrathiomolybdic acid;thiobarbituric acid reactive substance/ec [Endogenous Compound],"Sugawara, N.;Ikeda, T.;Lai, Y. R.;Sugawara, C.",1999,,,0,0,
2423,Hepatology,,bile duct disease/si [Side Effect];clinical trial;drug overdose/dt [Drug Therapy];early diagnosis;hemochromatosis/di [Diagnosis];hepatitis B/dt [Drug Therapy];hepatitis B/su [Surgery];hepatitis C/dt [Drug Therapy];herbal medicine;homozygote;human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver disease/su [Surgery];liver failure/dt [Drug Therapy];liver toxicity/dt [Drug Therapy];liver toxicity/si [Side Effect];liver transplantation;living donor;mortality;priority journal;short survey;subcutaneous drug administration;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];aceprometazine/ae [Adverse Drug Reaction];acetylcysteine/dt [Drug Therapy];ajmaline/ae [Adverse Drug Reaction];alpha interferon/cb [Drug Combination];alpha interferon/dt [Drug Therapy];amineptine/ae [Adverse Drug Reaction];amitriptyline/ae [Adverse Drug Reaction];amoxicillin plus clavulanic acid/ae [Adverse Drug Reaction];ampicillin/ae [Adverse Drug Reaction];arsenic derivative/ae [Adverse Drug Reaction];azathioprine/ae [Adverse Drug Reaction];barbituric acid derivative/ae [Adverse Drug Reaction];carbamazepine/ae [Adverse Drug Reaction];carbutamide/ae [Adverse Drug Reaction];chlorpromazine/ae [Adverse Drug Reaction];cotrimoxazole/ae [Adverse Drug Reaction];cyamemazine/ae [Adverse Drug Reaction];erythromycin/ae [Adverse Drug Reaction];flucloxacillin/ae [Adverse Drug Reaction];lamivudine/ct [Clinical Trial];lamivudine/dt [Drug Therapy];methyltestosterone/ae [Adverse Drug Reaction];paracetamol/to [Drug Toxicity];penicillamine/dt [Drug Therapy];phenytoin/ae [Adverse Drug Reaction];plant extract/ae [Adverse Drug Reaction];prochlorperazine/ae [Adverse Drug Reaction];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];unindexed drug;zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"McCarthy, M.;Wilkinson, M. L.",1999,08 May,,0,0,
2424,Copper associated acute hepatic failure in a dog,"A 1.5-year-old Dalmatian was examined because of vomiting, weight loss, and high serum activities of alanine aminotransferase and aspartate aminotransferase. Abdominal ultrasonography revealed normal appearing hepatic structure with echogenicity, but histologic examination of hepatic biopsy specimens revealed extensive necrosis of hepatocytes involving the centrilobular areas. Macrophages and remaining hepatocytes contained pigments that were positive for copper by rubeanic acid-staining and hepatic copper concentration was high. The dog was treated with crystalloid fluids, antibiotics, and a low copper diet; its condition deteriorated, and the dog was euthanatized. Primary copper storage disease was suspected on the basis of histologic findings and high copper concentration in the liver.",acute disease;animal experiment;animal model;animal tissue;article;controlled study;differential diagnosis;dog;intestine absorption;liver biopsy;liver failure/di [Diagnosis];nonhuman;oral drug administration;subcutaneous drug administration;urinary excretion;chelating agent;copper/to [Drug Toxicity];dye;lactulose;penicillamine;phytomenadione;prochlorperazine;rubeanic acid;sodium chloride;unclassified drug,"Noaker, L. J.;Washabau, R. J.;Detrisac, C. J.;Heldmann, E.;Hendrick, M. J.",1999,15 May,,0,0,
2425,Zinc and manganese in the schizophrenias,"The essential trace elements zinc and manganese have been noted as factors in brain disease since the 1920s. The combined use of zinc and manganese in schizophrenia is based on: 1) Increased urinary excretion of copper when both zinc and manganese are given orally; 2) Zinc alone causes a decrease in blood manganese; 3) The double deficiency of zinc and manganese frequently is found in patients with excess copper. The mauve factor (Kryptopyrrole) is known to increase the excretion of zinc and vitamin B<inf>6</inf> (pyridoxine). In children, insufficient levels of zinc and manganese have been associated with lowered learning ability, apathy, lethargy and mental retardation. Hyperactive children may be deficient in zinc, manganese and vitamin B<inf>6</inf> and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc and manganese levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of shizophrenia. Manganese is important in the building and breakdown cycles of protein and nucleic acid. For RNA chain initiation, manganese was found to be a better effector than magnesium. Manganese stimulates adenylate cyclase activity in brain tissue. Because cyclic-AMP plays a regulatory role in the action of several brain neurotransmitters, manganese is important in brain function. Owing to the fact that zinc is well absorbed from the gut but manganese is poorly absorbed all diagnostic categories may be harmed by large prolonged oral doses of zinc without manganese. In oral doses manganese occasionally elevates blood pressure in patients over 40 years of age. Zinc alone can lower blood pressure in some hypertensive patients. Chronic user of hydralazine (a manganese chelator) in rats produced manganese deficiency which resulted in convulsions. Low blood and serum manganese levels may play a role in epilepsy possibly by interfering with membrane stability. Prolonged use of pheno-thiazines causes tardive dyskinesia. Phenothiazines might chelate manganese making it unavailable for some presumed function as an enzyme activator.",Alzheimer disease/dt [Drug Therapy];Alzheimer disease/et [Etiology];arthritis/dt [Drug Therapy];arthritis/si [Side Effect];article;brain development;diet supplementation;human;hypertension/dt [Drug Therapy];lead poisoning/dt [Drug Therapy];lead poisoning/et [Etiology];mental disease/dt [Drug Therapy];mental disease/et [Etiology];nausea/si [Side Effect];nonhuman;nutritional deficiency/dt [Drug Therapy];nutritional deficiency/et [Etiology];oral drug administration;Pick presenile dementia/dt [Drug Therapy];Pick presenile dementia/et [Etiology];schizophrenia/dt [Drug Therapy];schizophrenia/et [Etiology];seizure/et [Etiology];seizure/si [Side Effect];tardive dyskinesia/dt [Drug Therapy];tardive dyskinesia/si [Side Effect];vitamin deficiency/dt [Drug Therapy];vitamin deficiency/et [Etiology];zinc deficiency/dt [Drug Therapy];zinc deficiency/et [Etiology];amino acid;antihypertensive agent/ae [Adverse Drug Reaction];antihypertensive agent/dt [Drug Therapy];chelating agent/dt [Drug Therapy];copper;disulfiram/dt [Drug Therapy];edetate calcium/dt [Drug Therapy];folic acid;histamine;hydralazine/ae [Adverse Drug Reaction];hydralazine/dt [Drug Therapy];manganese/ad [Drug Administration];manganese/cb [Drug Combination];manganese/do [Drug Dose];manganese/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];nicotinic acid/do [Drug Dose];nicotinic acid/dt [Drug Therapy];pyridoxine/ad [Drug Administration];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];pyridoxine/to [Drug Toxicity];zinc/ae [Adverse Drug Reaction];zinc/ad [Drug Administration];zinc/cb [Drug Combination];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/to [Drug Toxicity];zinc/pk [Pharmacokinetics],"Pfeiffer, C. C.;LaMola, S.",1999,First Quarter,,0,0,
2426,Pediatric movement disorders,"Movement disorders in children encompass disorders of motor control - both hyperkinetic (excessive movement) and hypokinetic (decreased movement). This article focuses on the hyperkinetic movement disorders, particularly tremor, Wilson's disease, dystonia, tics and Tourette syndrome, chorea, myoclonus, neuroleptic-induced movement disorders, and psychogenic movement disorders. Phenomenology of the disorders as well as clinical presentation, basic pathophysiology, genetics, and treatment are discussed.",adolescent;body weight disorder/si [Side Effect];child;chorea/di [Diagnosis];clinical feature;dystonia/di [Diagnosis];dystonia/dt [Drug Therapy];dystonia/si [Side Effect];dystonia/su [Surgery];Gilles de la Tourette syndrome/di [Diagnosis];Gilles de la Tourette syndrome/dt [Drug Therapy];heredity;human;hyperkinesia/di [Diagnosis];hyperkinesia/dt [Drug Therapy];hyperkinesia/si [Side Effect];hyperkinesia/su [Surgery];hypokinesia/di [Diagnosis];motor dysfunction/di [Diagnosis];motor dysfunction/dt [Drug Therapy];motor dysfunction/si [Side Effect];motor dysfunction/su [Surgery];myoclonus/di [Diagnosis];myoclonus/dt [Drug Therapy];pathophysiology;pediatrics;phenomenology;priority journal;review;tic/di [Diagnosis];tic/dt [Drug Therapy];tremor/di [Diagnosis];tremor/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];anticonvulsive agent/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];clonazepam/dt [Drug Therapy];clonidine/dt [Drug Therapy];dopamine receptor blocking agent/ae [Adverse Drug Reaction];dopamine receptor blocking agent/dt [Drug Therapy];fluphenazine/dt [Drug Therapy];gabapentin/dt [Drug Therapy];haloperidol/ae [Adverse Drug Reaction];haloperidol/dt [Drug Therapy];levodopa/dt [Drug Therapy];molindone/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pimozide/ae [Adverse Drug Reaction];pimozide/dt [Drug Therapy];primidone/dt [Drug Therapy];risperidone/ae [Adverse Drug Reaction];risperidone/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];tiotixene/dt [Drug Therapy];unindexed drug/dt [Drug Therapy];valproic acid/dt [Drug Therapy],"Saunders-Pullman, R.;Braun, I.;Bressman, S.",1999,,,0,0,
2427,Schizophrenia-like symptoms in the Westphal-Strumpell form of Wilson's disease [2],,adolescent;adult;anorexia/et [Etiology];apathy;case report;child;computer assisted tomography;delusion/dt [Drug Therapy];delusion/et [Etiology];diagnostic error;human;letter;male;mania/dt [Drug Therapy];nuclear magnetic resonance imaging;priority journal;suicide/et [Etiology];wakefulness;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alprazolam/dt [Drug Therapy];biperiden/dt [Drug Therapy];haloperidol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pipamperone/dt [Drug Therapy];thioridazine/dt [Drug Therapy];zuclopenthixol/dt [Drug Therapy],"Muller, J. L.",1999,,,0,0,
2428,Long-term follow-up of combined therapy with large-dose zinc sulfate and low-dose penicillamine in children with hepatolenticular degeneration. [Chinese],"Objective To summarize the long-term effect of combined treatment with large-dose zinc sulfate and low-dose penicillamine in children with hepatolenticular degeneration (HLD). Methods The patients who had symptoms were treated with large-dose zinc sulfate (100-1 50mg, <6yr;150-200mg, 6- 8yr; 200-300mg, 9-10yr; 300mg, > 10yr; 3 times a day) in addition to low- dose penicillamine (8-10mg/kg/d) at the beginning of treatment. Zinc sulfate alone was given to the presymptomatic patients and it was used as maintenance therapy when clinical improvement was obtained. 31 children were followed up for 4-11 years. Results In 3 presymptomatic patients, no clinical abnormalities were found. Among 28 patients with symptoms, 23 patients (82%) had their symptoms and signs subsided or much improved, 2 patients (7%) remained unchanged, and 3 (11%) died. Blood concentrations of copper were persistently lower than normal. Urine copper excretion of 24 hours was significantly lower than that before the combined therapy in all patients, and it became normal in 5 cases (16%) after 6 months of treatment, and in 26 cases (84%) after 1-2 years of treatment. Higher blood concentrations of zinc were found in 20 cases (65%), and higher urine zinc excretion was noted in 25 cases (81%) once or more times during the therapy. Conclusion Combined therapy of large-dose zinc sulfate and low-dose penicillamine is an effective, safe and cheap treatment for children with HLD.",Hepatolenticular degeneration;Penicillamine Children;Zinc sulfate;article;child;drug cost;drug efficacy;drug safety;follow up;human;maintenance therapy;symptomatology;treatment outcome;Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];zinc blood level;penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pe [Pharmacoeconomics];penicillamine/pd [Pharmacology];zinc sulfate/cb [Drug Combination];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy];zinc sulfate/pe [Pharmacoeconomics];zinc sulfate/pd [Pharmacology],"Li, T.;Lin, R.;Du, S.;Qu, Z.",1999,,,0,0,
2429,Computer simulation of Wilson's disease and its treatment with D-penicillamine,"Wilson's disease and its treatment with D-penicillamine was studied by computer simulation. For proper simulation of Wilson's disease it was necessary to consider a separate form of liver copper and for treatment a separate urinary excretion of a D-penicillamine copper. Both have been suggested, but not previously demonstrated. These simulations support the conclusion that the liver is not 'de-coppered' by D-penicillamine neither in Wilson's disease patients nor in normal individuals. These findings are in accord with current research on the molecular biology of Wilson's disease and support conclusions that the D-penicillamine-copper complex may facilitate redistribution of copper to enable physiological and biochemical responses required to overcome the liver inflammatory disease associated with Wilson's disease.",Computer simulation;Copper;D-penicillamine;Wilson's disease;article;complex formation;hepatitis/co [Complication];hepatitis/et [Etiology];liver level;molecular biology;priority journal;urine level;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];chelating agent/dt [Drug Therapy];copper complex;copper ion/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Blincoe, C.;Sorenson, J. R. J.",1999,,,0,0,
2430,The treatment of wilson's disease,,clinical feature;conference paper;drug blood level;drug efficacy;drug mechanism;drug safety;follow up;human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver transplantation;maintenance therapy;nonhuman;patient compliance;patient monitoring;practice guideline;pregnancy;priority journal;prognosis;side effect/si [Side Effect];teratogenicity/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/ae [Adverse Drug Reaction];penicillamine/cr [Drug Concentration];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology];trientine/cr [Drug Concentration];trientine/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/cr [Drug Concentration];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],"Brewer, G. J.",1999,,,0,0,
2431,Therapeutic effects of tetrathiomolybdate on hepatic dysfunction occurring naturally in Long-Evans Cinnamon (LEC) rats: A bona fide animal model for Wilson's disease,"Long-Evans Cinnamon (LEC) rats were fed a diet containing 7 ppm Cu and 30 ppm Cu from 60 days after birth. Fischer (Fischer group) and LEC (LEC- control group) rats fed a 7 ppm Cu diet showed normal growth throughout the whole period (60 to 125 days after birth). On the other hand, LEC rats fed the 30 ppm Cu diet had decreased body weight and showed slight jaundice at around 100 days after birth. Tetrathiomolybdate (TTM, 10 mg/kg bw) was injected sub-cutaneously at 101 and 105 days after birth into half of the LEC rats fed the 30 ppm Cu diet. LEC rats given TTM (LEC+TTM group) recovered their body weight and the jaundice rapidly disappeared. However, LEC rats without TTM (LEC-TTM group) had sharply decreased body weight and showed severe jaundice at 103 days after birth. The hepatic Cu concentration in LEC+TTM rats (460 mug/g) exceeded that of LEC-control rats (330 mug/g) at 125 days after birth. Our data suggest that TTM is effective for treatment of acute hepatic injury in the LEC rat.",animal experiment;animal model;article;bile secretion;biliary excretion;body weight;controlled study;copper metabolism;drug effect;jaundice;liver disease;liver function;liver protection;nonhuman;priority journal;rat;sampling;Wilson disease;tetrathiomolybdic acid/pd [Pharmacology],"Sugawara, N.;Lai, Y. R.;Sugawara, C.",1999,February,,0,0,
2432,"Preventive effect of zinc compounds, polaprezinc and zinc acetate against the onset of hepatitis in Long-Evans Cinnamon rat","It is known that Long-Evans Cinnamon (LEC) rats are characterized by the fulminant hepatitis occurring as a result of an abnormal hepatic deposition of Cu due to the lack of the Cu-transporter p-type ATPase. To prevent the hepatitis, two Zn compounds, Zn acetate and polaprezinc were given orally to LEC rats aged 30 days. At 100 days after birth, the control group composed of LEC rats fed a basal diet (Cu, 17 ppm; Zn, 50 ppm; Fe, 150 ppm) exhibited slight jaundice and showed high activities of serum enzymes related to hepatic function. The groups fed the diet fortified (1000 ppm as Zn) with Zn acetate or polaprezinc did not have jaundice. The hepatic Cu concentrations were 174 +/- 34 mug/g and 156 +/- 23 mug/g in the polaplezinc group and Zn acetate group, respectively. The control group showed 267 +/- 17 mug Cu/g and 298 +/- 62 mug Fe/g in the liver. The Fe concentration was about 1.7 times the concentration in the two Zn groups. Hepatic free Cu and Fe concentrations were 2.6 +/- 0.3 and 21.4 +/- 5.8 mug/g, 1.7 +/- 0.7 and 6.8 +/- 1.1 mug/g, and 1.3 +/- 0.1 and 6.2 +/- 0.8 mug/g in the control, polaprezinc and zinc acetate groups, respectively. Intestinal metallothionein (MT) concentrations were not increased significantly by the Zn diets. The two Zn compounds inhibit Cu absorption from the intestinal tract, resulting in a decrease of hepatic Cu deposition. The new Zn compound as well as Zn acetate is categorized as a therapeutic drug for Cu poisoning, including Wilson's disease.",animal experiment;animal model;article;calcium absorption;calcium transport;cell survival;controlled study;drug effect;hepatitis;intestine mucosa;liver function;liver protection;membrane stabilization;nonhuman;priority journal;rat;Wilson disease;wound healing;metallothionein;penicillamine;polaprezinc/pd [Pharmacology];zinc acetate/pd [Pharmacology];zinc derivative/pd [Pharmacology],"Sugawara, N.;Katakura, M.;Sugawara, C.",1999,February,,0,0,
2433,Hepatolenticular degeneration (Wilson's disease),"BACKGROUND- Wilson's disease is a recessively inherited disorder in which homozygous mutation in the copper ATPase ATP7B gene (on chromosome 13) reduces the liver's ability to secrete ceruloplasmin into the plasma and to excrete it into the bile. REVIEW SUMMARY- Systemic copper accumulation leads to progressive hepatic dysfunction, neurologic impairment, psychiatric disturbance, or combinations of these symptoms. Wilson's disease is diagnosed by measuring 24-hour urine copper excretion, followed by measuring copper in a liver biopsy sample. Wilson's disease is treated by copper removal therapy (penicillamine or trientine), followed by maintenance therapy with zinc. Frequent exacerbation of neurologic impairment with penicillamine has prompted the use of tetrathiolmolybdate as an alternative decoppering agent. CONCLUSION- Wilson's disease should be considered in all patients with unexplained hepatic disturbance and those with unexplained, progressive movement disorders or psychiatric disturbance. Early diagnosis and appropriate treatment are essential. Tetrathiolmolybdate seems to be as effective as penicillamine and is associated with less frequent neurologic worsening compared with penicillamine.",Basal ganglia;Copper metabolism;Movement disorder;arthritis/si [Side Effect];bile secretion;ceruloplasmin blood level;clinical feature;copper blood level;early diagnosis;gene mutation;human;liver biopsy;liver dysfunction/et [Etiology];liver function;mental disease/et [Etiology];neurologic disease/et [Etiology];priority journal;prognosis;rash/si [Side Effect];review;thrombocytopenia/si [Side Effect];urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Fink, J. K.;Hedera, P.;Brewer, G. J.",1999,July,,0,0,
2434,Non-invasive diagnosis and management of chronic liver diseases,"Advances in computer-aided diagnosis, imaging techniques, DNA mutation analysis, virology, immunology and biochemistry have improved our understanding of chronic liver diseases and the possibilities for non-invasive diagnosis. Various medical therapies for chronic liver diseases and their complications have been developed and their monitoring has also improved. This review focuses on these recent advances in non-invasive diagnosis and management of chronic liver diseases.",Chronic liver disease;Cirrhosis;Clinical decision making;Complications;Diagnosis;Prognosis;Therapy;alcohol liver disease/di [Diagnosis];ascites/di [Diagnosis];autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];autoimmune hepatitis/et [Etiology];autoimmune hepatitis/su [Surgery];bacterial peritonitis/co [Complication];bacterial peritonitis/di [Diagnosis];Budd Chiari syndrome/di [Diagnosis];cholestatic hepatitis/di [Diagnosis];cholestatic hepatitis/et [Etiology];chronic liver disease/co [Complication];chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];chronic liver disease/et [Etiology];chronic liver disease/pc [Prevention];chronic liver disease/si [Side Effect];chronic liver disease/su [Surgery];chronic liver disease/th [Therapy];diagnostic imaging;drug hypersensitivity/si [Side Effect];esophagus varices bleeding/co [Complication];esophagus varices bleeding/dt [Drug Therapy];esophagus varices bleeding/pc [Prevention];fatty liver/di [Diagnosis];hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/et [Etiology];hemochromatosis/su [Surgery];hepatic encephalopathy/co [Complication];hepatic encephalopathy/di [Diagnosis];hepatopulmonary syndrome/co [Complication];hepatopulmonary syndrome/di [Diagnosis];hepatorenal syndrome/co [Complication];hepatorenal syndrome/di [Diagnosis];human;liver cell carcinoma/co [Complication];liver cell carcinoma/di [Diagnosis];liver cirrhosis/di [Diagnosis];liver transplantation;liver venoocclusive disease/di [Diagnosis];lymphatic system disease/si [Side Effect];malnutrition/co [Complication];malnutrition/dt [Drug Therapy];neurotoxicity/si [Side Effect];oral drug administration;osteoporosis/dt [Drug Therapy];osteoporosis/pc [Prevention];osteoporosis/si [Side Effect];portal vein thrombosis/di [Diagnosis];primary biliary cirrhosis/di [Diagnosis];primary biliary cirrhosis/dt [Drug Therapy];primary biliary cirrhosis/et [Etiology];primary biliary cirrhosis/su [Surgery];primary sclerosing cholangitis/di [Diagnosis];primary sclerosing cholangitis/dt [Drug Therapy];primary sclerosing cholangitis/et [Etiology];primary sclerosing cholangitis/su [Surgery];pruritus/co [Complication];pruritus/dt [Drug Therapy];pruritus/pc [Prevention];review;toxic hepatitis/di [Diagnosis];toxic hepatitis/et [Etiology];toxic hepatitis/si [Side Effect];virus hepatitis/di [Diagnosis];virus hepatitis/dt [Drug Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];alpha interferon/cb [Drug Combination];alpha interferon/do [Drug Dose];alpha interferon/dt [Drug Therapy];anesthetic agent/ae [Adverse Drug Reaction];anticonvulsive agent/ae [Adverse Drug Reaction];antidepressant agent/ae [Adverse Drug Reaction];antirheumatic agent/ae [Adverse Drug Reaction];antivirus agent/cb [Drug Combination];antivirus agent/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];bisphosphonic acid derivative/cb [Drug Combination];bisphosphonic acid derivative/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/cb [Drug Combination];chelating agent/dv [Drug Development];chelating agent/do [Drug Dose];chelating agent/dt [Drug Therapy];ciprofloxacin/dt [Drug Therapy];colestyramine/dt [Drug Therapy];corticosteroid/ae [Adverse Drug Reaction];corticosteroid/cb [Drug Combination];corticosteroid/dt [Drug Therapy];dapsone/ae [Adverse Drug Reaction];deferoxamine/do [Drug Dose];deferoxamine/dt [Drug Therapy];immunosuppressive agent/cb [Drug Combination];immunosuppressive agent/dt [Drug Therapy];losartan/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];nucleoside analog/cb [Drug Combination];nucleoside analog/do [Drug Dose];nucleoside analog/dt [Drug Therapy];paracetamol/to [Drug Toxicity];phenylbutazone/ae [Adverse Drug Reaction];phenytoin/ae [Adverse Drug Reaction];procainamide/ae [Adverse Drug Reaction];pyridoxine/cb [Drug Combination];pyridoxine/do [Drug Dose];pyridoxine/dt [Drug Therapy];spironolactone/dt [Drug Therapy];terbinafine/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];tuberculostatic agent/ae [Adverse Drug Reaction];unindexed drug;vitamin/dt [Drug Therapy];zinc/dt [Drug Therapy],"Van Hoek, B.",1999,,,0,0,
2435,Combined therapy with D-penicillamine and zinc salts in a case of Wilson's disease with chorea and cognitive dysfunction. [Spanish],"We report the case of a female patient with chorea and cognitive disorders due to Wilson's disease with cerebral and hepatic involvement. Under treatment with D-penicillamine and zinc salts she initially evidenced worsening of the motor function, with cognitive stability. After adjustment of the D-penicillamine schedule both processes improved, with a more favourable course for the superior functions.",Chorea;Cognitive dysfunction;D-penicillamine;Wilson's disease;Zinc;adult;amenorrhea;article;case report;cataract;cognitive defect;Fanconi renotubular syndrome;female;hemolytic anemia;human;hypoparathyroidism;liver disease;motor performance;nephrolithiasis;nuclear magnetic resonance imaging;portal hypertension;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Amorin, M.;Alvarez, J. C.;Parra, T.;Fernandez, J. M.;Calleja, S.;Suarez-Moro, R.;Hernandez, C.",1999,,,0,0,
2436,Anesthetic management of a patient with Wilson's disease. [Japanese],"Wilson's disease, which is characterized by cirrhosis, extrapyramidal symptoms and Kayser-Fleischer corneal rings, is a rare congenital disorder with abnormal copper metabolism. In spite of many anesthetic problems, there are no reports in the field of dental anesthesiology. We report an anesthetic management case with Wilson's disease. The patient was a 24-year-old male who was scheduled for extraction of many teeth. He was diagnosed with Wilson's disease at the age of 11 years and treated with D-penicillamin. He was complicated with cirrhosis, but the liver laboratory profiles were normal without slight elevations of ZTT (12.6U) and TTT (5.2U) (Table 1). Esophageal varices had been treated by endoscopic varicosclerosation two years previously. Concentrations of serum copper (16 mug/dl) and ceruloplasmin (less than 0.4 mg/dl) were decreased remarkably, and urinary copper excretion was increased (130 mug/dl). He had extrapyramidal symptoms such as dysarthria, involuntary movement, and muscle rigidity, but intellectual function was preserved. After induction of anesthesia with thiamylal, vecuronium, nitrous oxide, oxygen, and isoflurane, general anesthesia was maintained with nitrous oxide, oxygen, and isoflurane (Fig. 1). Because the effect of vecuronium was expected to be prolonged due to liver disfunction, we monitored the degree of neuromuscular blockade with nerve stimulator, but the recovery from muscle relaxation was normal. During the operation, the ECG began to show first-degree AV block and then progressed to second-degree AV block (Wenckebach type) (Fig. 2). Second-degree AV block disappeared after administration of atropine sulfate (0.5 mg), and the hemodynamic state of the patient was stable until the end of surgery. No severe complications were encountered throughout the operation. No postoperative deterioration of liver or renal function or extrapyramidal symptoms was observed. The majority of Wilsonian patients respond to treatment with penicillamine, allowing them to resume a normal life. Because of involuntary movement or muscle rigidity, general anesthesia may be necessary for their dental treatment. We emphasize the need for sufficient preoperative screening of cardiac involvement such as electrocardiographic abnormalities and cardiomyopathy, as well as preoperative evaluation of liver function. In addition, it was also necessary to consider the side effects of D-penicillamin such as myasthenia gravis and fever.",Extrapyramidal symptom;General anesthesia;Oral surgery;Penicillamine;Wilson's disease;adult;anesthesia induction;article;case report;clinical feature;heart block;human;liver cirrhosis;male;neuromuscular blocking;tooth extraction;Wilson disease;anesthetic agent;atropine;ceruloplasmin;copper;isoflurane;nitrous oxide;thiamylal;vecuronium,"Tanaka, K.;Kamekura, N.;Teramoto, T.;Kimura, Y.;Fukushima, K.",1999,,,0,0,
2437,Immunohistochemical determination of the Wilson Copper-transporting P- type ATPase in the brain tissues of the rat,"Immunohistochemical localization of Copper-transporting P-type ATPase (ATP7B), a gene product responsible for Wilson disease, was visualized in the brain tissues of the Long-Evans agouti rat in detail using tissue-blotting technique and confocal laser microscopy. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brainstem in which high amounts of copper and cuproenzymes, dopamine beta hydroxylase and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) were detected. The present results suggest that ATP7B plays key roles in neurotransmissions of catecholamine pathway and preventing brain tissues from injury by superoxide radicals to regulate the cellular Cu concentration and/or activities of cuproenzymes related to neurotransmissions and a free radical metabolism. Furthermore, it is reasonable to assume that neurotoxicity due to abnormal copper accumulation or irregular regulation of cuproenzymes in the critical brain regions by mutation of the ATP7B gene leads to neurological failures of Wilson disease.",atp7b;Brain;Copper transport;Histochemistry;Wilson disease;animal cell;animal tissue;article;catecholamine release;confocal laser microscopy;enzyme analysis;immunohistochemistry;male;neurotoxicity/di [Diagnosis];nonhuman;priority journal;protein localization;rat;signal transduction;tissue distribution;Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];copper;gene product,"Saito, T.;Okabe, M.;Hosokawa, T.;Kurasaki, M.;Hata, A.;Endo, F.;Nagano, K.;Matsuda, I.;Urakami, K. I.;Saito, K.",1999,30 Apr,http://dx.doi.org/10.1016/S0304-3940%2899%2900258-X,0,0,
2438,Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease - Possible association with a steroid-resistant transplant rejection episode,"Background/Aims: Antibodies to cytochrome P450 2D6, also known as LKM1- autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis C. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis C. Methods: Sera from several time points prior to and following transplantation were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting. Antigen specificity was confirmed by Western blotting analysis on different cytochrome P450 isoenzymes. The absence of viral hepatitis C and hepatitis G virus infection was confirmed by polymerase chain reaction. The serum of the organ donor was also tested. Results: All the sera prior to transplantation and up to 4 months after transplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed LKM antibodies at high titre (70% in inhibition ELISA) and has remained positive since (now more than 4 years). Reactivity was exclusively to the cytochrome isoenzyme 2D6. Hepatitis C infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor serum was negative for all autoantibodies and for hepatitis C and G virus infection. Discussion: We here describe a patient developing LKM1-autoantibodies without evidence of autoimmune or viral hepatitis. The close temporal association with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.",Cytochrome P450 2D6;Liver transplantation;LKM-autoantibodies;Transplant rejection;Wilson's disease;adult;antibody specificity;article;autoimmune hepatitis/di [Diagnosis];autoimmunity;case report;clinical feature;differential diagnosis;disease course;graft rejection/di [Diagnosis];graft rejection/dt [Drug Therapy];graft rejection/et [Etiology];graft rejection/pc [Prevention];hepatitis C/di [Diagnosis];human;human tissue;immunopathogenesis;immunosuppressive treatment;liver histology;male;priority journal;serodiagnosis;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];azathioprine/cb [Drug Combination];azathioprine/dt [Drug Therapy];debrisoquine 4 hydroxylase/ec [Endogenous Compound];microsome antibody/ec [Endogenous Compound];OKT 3/cb [Drug Combination];OKT 3/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisolone/cb [Drug Combination];prednisolone/dt [Drug Therapy];zinc/dt [Drug Therapy],"Lohse, A. W.;Obermayer-Straub, P.;Gerken, G.;Brunner, S.;Altes, U.;Dienes, H. P.;Manns, M. P.;Buschenfelde, K. H. M. Z.",1999,July,http://dx.doi.org/10.1016/S0168-8278%2899%2980175-5,0,0,
2439,Wilson's disease: Copper unfettered,"Wilson's disease is a rare autosomal recessive inherited disorder of copper metabolism. Hepatic excretion of copper is impaired due to mutation of the gene for a copper-transporting adenosine triphosphatase, ATP7B. Copper accumulation in liver, brain, and other tissues may cause a wide spectrum of hepatic, neuropsychiatric, and other clinical manifestations. The diagnosis may be supported by measurement of serum ceruloplasmin, urinary copper excretion, and hepatic copper content as well as by detection of Kayser- Fleischer rings. Several treatments are available to increase urinary excretion and decrease intestinal absorption of copper.",Cirrhosis;Copper metabolism;Hepatolenticular degeneration;Wilson's disease;animal experiment;animal model;autosomal recessive disorder;clinical feature;dietary intake;enzyme blood level;gene mutation;intestine absorption;liver transplantation;nonhuman;pathophysiology;plasmapheresis;priority journal;rat;review;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];adenosine triphosphatase;antioxidant/dt [Drug Therapy];ceruloplasmin;copper;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Pfeil, S. A.;Lynn, D. J.",1999,July,http://dx.doi.org/10.1097/00004836-199907000-00007,0,0,
2440,The presence of an Na<sup>+</sup>/spermine antiporter in the rat renal brush-border membrane,"This study was aimed at determining the driving force for spermine transport in rat renal proximal tubular brush-border membrane. The uptake of spermine and trientine, a spermine-like drug used for treating Wilson's disease, into rat renal brush-border membrane vesicles was significantly stimulated by an outwardly directed Na<sup>+</sup> gradient. The Na<sup>+</sup>-dependent uptake was temperature dependent and saturable. A kinetic analysis of the initial uptake of spermine with an Na<sup>+</sup> gradient gave a K(m) value of 1.44 muM and a V(max) value of 6.31 pmol (mg protein)<sup>-1</sup>/30 s. The Na<sup>+</sup>-dependent uptake of [<sup>3</sup>H]spermine was inhibited by spermine, trientine and tetraethylenepentamine. Substrates of the H<sup>+</sup>/organic cation transporter (cimetidine and tetraethylammonium), physiological polyamines (putrescine and spermidine) with 2 or 3 amino groups and aminoglycosides (amikacin and tobramicin) with 4 or 5 cationic amines did not affect the uptake of spermine in the presence of an outwardly directed Na<sup>+</sup> gradient. These results suggest that the renal tubular secretion of spermine is mediated by an Na<sup>+</sup>/spermine antiport system which is specific for a straight-chain polyamine compound with more than 4 amino groups.",amine transport;animal cell;article;brush border;controlled study;incubation time;isotope labeling;kidney tubule epithelium;nonhuman;pH;rat;sodium transport;temperature sensitivity;amikacin;aminoglycoside;antiporter/ec [Endogenous Compound];cimetidine;polyamine/ec [Endogenous Compound];putrescine;sodium ion/ec [Endogenous Compound];spermidine;spermine/ec [Endogenous Compound];tetrylammonium;tobramycin;trientine/pk [Pharmacokinetics],"Kobayashi, M.;Fujisaki, H.;Sugawara, M.;Iseki, K.;Miyazaki, K.",1999,March,,0,0,
2441,Hepatic hereditary metabolic disorders of metals. [Slovak],"The authors deal with hereditary metabolic disorders of metals causing liver damage, mainly hereditary metabolic diseases of copper and iron. Copper is an essential metal in the organism that facilitates electrone transmission in many critical biologic reactions and it is a component of numerous biologically important enzymes. Of hereditary metabolic diseases of copper, Wilson disease is the most important, as it is still diagnosed too late, in the stage of severe liver damage. New knowledge in pathogenesis is being stressed - gene for P-type of ATP-ase ATP 7B (so-called WD protein) on the chromosome 13q14.3, deficiency of Cu transport from the cell through the cellular membrane, i.e. Cu excretion into the bile, persistent fetal Cu metabolism with prevalent metalothionein instead of ceruloplasmin, complex approach in the diagnostics, and new treatment approaches (zinc). The authors analyze the complexity of hereditary hemochromatosis emphasizing its frequent incidence, knowledge in genetics - mutation of HLA-H gene (HFE), Fe deposits in tissues and fibrosis stimulation by monocytes, and mechanism of developing of bronze diabetes. As screening they recommend the examination of transferin saturation (above 50 % is highly suspective hemochromatosis), ferritin concentration above 1000 mug/l, gene analysis, liver biopsy and significance of imaging methods. In the treatment the authors emphasize the removal of Fe over-supply and in prognosis they point at the risk of hepatocellular carcinoma.",atp 7b;ATP-ase P-type;Hereditary hemochromatosis;hla-h;Kinky hair syndrome;Menkes disease;Syndrome of occipital horns;Treatment by zinc;Wilson disease;article;chromosome 13q;copper deficiency;copper metabolism;genetic analysis;hemochromatosis;inborn error of metabolism/cn [Congenital Disorder];liver biopsy;liver cell carcinoma;liver injury;ceruloplasmin;copper;ferritin;iron;transferrin,"Sasinka, M.;Krusovsky, S.;Kovacova, M.",1999,,,0,0,
2442,Hepatic hyperplasia and cancer in rats: Alterations in copper metabolism,"We previously demonstrated that rats exposed to the peroxisome proliferator (PP) diethylhexylphthalate (DEHP) had reduced serum ceruloplasmin (CP) oxidase activity, which suggests tissue copper deposition. Copper is highly toxic in excess, and results in cellular damage and hepatocellular carcinomas (HCC). This study addresses changes in expression of copper-related genes and metal accumulation in hyperplastic liver and tumors induced by PP. Male rats were fed diets containing DEHP or clofibrate (CLF) for 3-60 days (hyperplasia) and 4-chloro-6-(2,3 xylidino)-2-pyrimidinyl-thio(N-beta-hydroxyethyl) acetamide for 10 months (HCC). During hyperplasia, an immediate and progressive decrease in serum CP activity was observed (P < 0.05), as were reductions in mRNA levels for both CP and Wilson's disease gene (WD gene, a P-type ATPase) (P < 0.05), tumor-bearing rats had lower serum CP activity (P < 0.05), and CP and WD gene mRNA levels were reduced in tumors (P < 0.05), and in liver surrounding tumors (SL) (P < 0.05). Metallothionein mRNA showed no consistent changes during hyperplasia. Tumors showed a 2.5-fold induction of metallothionein mRNA (P < 0.05), and a 1.2-fold increase in SL. Temporal increases in liver copper content occurred during hyperplasia, with increases of 2-fold (DEHP) and 3,3-fold (CLF) at 60 days (P < 0.05). Copper content was 2.2-fold higher in tumors (P < 0.05) and 1.7-fold higher in SL; iron did not increase and zinc decreased temporally. Thus, copper accumulation and changes in copper-related gene expression may be contributing factors in liver neoplasia in PP-treated rats. Loss of CP results in decreased free radical scavenger capacity and thus may enhance oxidative damage induced by PPs.",animal experiment;animal model;animal tissue;article;cell damage;ceruloplasmin blood level;controlled study;copper metabolism;disease course;enzyme activity;gene expression;human;liver cancer/et [Etiology];liver cell carcinoma/et [Etiology];liver hyperplasia/et [Etiology];liver tumor/et [Etiology];male;metal metabolism;nonhuman;oxidation;priority journal;rat;tissue;Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];clofibrate;copper;iron/ec [Endogenous Compound];messenger RNA/ec [Endogenous Compound];metal;metallothionein/ec [Endogenous Compound];peroxisome proliferator;phthalic acid bis(2 ethylhexyl) ester;pirinixil;scavenger/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Eagon, P. K.;Teepe, A. G.;Elm, M. S.;Tadic, S. D.;Epley, M. J.;Beiler, B. E.;Shinozuka, H.;Rao, K. N.",1999,,http://dx.doi.org/10.1093/carcin/20.6.1091,0,0,
2443,Hepatic retinopathia: Changes in retinal function (multiple letters),,bioaccumulation;copper metabolism;cornea endothelium;hepatic encephalopathy/co [Complication];hepatic encephalopathy/et [Etiology];human;jaundice/co [Complication];jaundice/et [Etiology];letter;liver failure/et [Etiology];priority journal;retinopathy/co [Complication];retinopathy/et [Etiology];Wilson disease/cn [Congenital Disorder];Wilson disease/et [Etiology];zinc metabolism;copper/to [Drug Toxicity];zinc/to [Drug Toxicity],"Kashani, A. A.;Eckstein, A.;Zrenner, E.",1999,,http://dx.doi.org/10.1016/S0042-6989%2898%2900267-3,0,0,
2444,Liver transplantation for Wilson's disease,"Liver transplantation is the sole etiological therapy for Wilson's disease and is the treatment of choice for Wilson's disease presenting as fulminant hepatic failure and for Wilson's disease patients with end-stage cirrhosis. The effect of liver transplantation on the neurological manifestations of the disease has been assessed in a few patients. We analyzed our personal data with literature reports on Wilson's disease patients with neurological symptoms who underwent liver transplantation, obtaining information on 40 patients. The transplant cured or improved the neurological symptoms in 32 of them (80%). This favorable outcome raises the question of whether liver transplantation should also be offered to patients with neurological Wilson's disease but stable liver function. Given the still high mortality after liver transplantation, the neurological status in Wilson's disease patients with stable liver function cannot be a general indication for liver transplantation, which in these cases has still to be considered experimental. Notwithstanding, liver transplantation could be entertained in patients with severely disabling medically intractable neurological deterioration, informing them thoroughly on the risks of surgery.",Liver transplantation;Neurological manifestations;Outcome;Wilson's disease;chelation therapy;conference paper;human;liver cirrhosis/su [Surgery];liver failure/su [Surgery];neurologic disease/cn [Congenital Disorder];neurologic disease/dt [Drug Therapy];neurologic disease/et [Etiology];neurologic disease/si [Side Effect];neurologic disease/th [Therapy];priority journal;surgical mortality;surgical risk;treatment outcome;Wilson disease/cn [Congenital Disorder];Wilson disease/et [Etiology];Wilson disease/su [Surgery];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];copper complex/ae [Adverse Drug Reaction];copper complex/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Stracciari, A.;Guarino, M.;Tempestini, A.;D'Alessandro, R.;Pazzaglia, P.",1999,,,0,0,
2445,Families of soft-metal-ion-transporting ATPases,"Within the last 5 years, much progress has been made in understanding the mechanism of action and evolution of soft-metal ATPases. The evolutionary pressure to flourish despite the geological omnipresence of metals has ensured that gene families for soft-metal resistances are not confined to a single species or even a single kingdom. Many questions remain to be answered, and we look forward to an accelerated acquisition of knowledge in the near future. One question is the function of ArsA homologues. Clearly in bacteria the arsA gene encodes the catalytic subunit of the ArsAB pump. It is not known whether the eukaryotic and archeal arsA homologues are orthologues or encode proteins with unrelated functions. Eukaryotes have resistance mechanisms for arsenicals. In both Leishmania and Chinese hamster cells we have shown that resistance is related to active extrusion of arsenite (44). But at this time the genes or gene products that produce the resistance have not been identified. A second question is the distribution of chaperones for soft metals in bacteria. While homologues of copper chaperones such as Atx1p and Lys7p are widely distributed in eukaryotes (12), they do not appear to exist in bacteria. CopZ serves a chaperone function in E. hirae (10), but homologues with copper chaperone activity have not been found in other bacteria. Additionally, it is not clear whether cells require chaperones for non-redox-active metals such as Zn(II), Cd(II), and Pb(II). A third question is the distribution of ZntA homologues in nature. The related Cu(I)- translocating P-type ATPases are found in most organisms. In humans these pumps are required for copper homeostasis, and mutations in either the ATP7A or ATP7B gene produce inborn errors of copper metabolism, resulting in Menkes or Wilson disease, respectively. Even though zinc is not as toxic as copper, in part because it is not a redox-active metal, it is still toxic in excess, and mechanisms to prevent overaccumulation must be present. To date a growing number of zntA and cadA genes for zinc-translocating P-type ATPases have been identified. Genes for putative ATP-dependent zinc pumps are being discovered in other kingdoms, for example in the genome of the archeaon Methanobacterium thermoautotrophicum (GenBank accession no. 2621474) and in the genome of the plant A. thaliana (GenBank accession no. 4210504). Within the next 5 years the sequencing of the human genome - and many others - will be completed. At that point the phylogenic distribution of zinc pumps and their involvement in human health and disease will be better understood.",antibiotic resistance;electron transport;gene;homeostasis;nonhuman;nucleotide sequence;operon;priority journal;repressor gene;short survey;transport and binding phenomena;adenosine triphosphatase/ec [Endogenous Compound];adenosine triphosphate derivative;antibiotic agent;antimony;arsenic;arsenic acid;cadmium;calcium;copper;lead;metal ion;silver;sodium;thioredoxin;zinc,"Rensing, C.;Ghosh, M.;Rosen, B. P.",1999,October,,0,0,
2446,Short interval change of <sup>99m</sup>Tc-ethyl cysteinate dimer single photon emission computed tomography in Wilson's disease. [Japanese],"We studied short interval change of cranial computed tomography (CT), magnetic resonance imaging (MRI) and <sup>99m</sup>Tc-ethyl cysteinate dimer single photon emission computed tomography (<sup>99m</sup>Tc-ECD SPECT) in a case of Wilson's disease. Before treatment, CT scan showed low density changes in the bilateral thalamus and basal ganglia, and MRI demonstrated high intensity in same lesions. <sup>99m</sup>Tc-ECD SPECT study revealed a hypoperfusion in bilateral thalamus. After 2 months under D-penicillamine therapy, neurological findings had improvement. Hypoperfusion in the thalamus with <sup>99m</sup>Tc-ECD SPECT significantly improved, whereas abnormal findings of CT scan and MRI persisted. <sup>99m</sup>Tc-ECD SPECT study may be useful for the planning of the treatment of Wilson's disease.",<sup>99m</sup>Tc-ECD SPECT;D-penicillamine;mri;Wilson's disease;adult;article;basal ganglion;case report;computer assisted tomography;female;human;nuclear magnetic resonance imaging;single photon emission computer tomography;thalamus;treatment planning;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];cysteine ethyl ester tc 99m;penicillamine/dt [Drug Therapy],"Imai, N.;Nozaki, H.;Miyata, K.;Terayama, Y.;Ishihara, N.",1999,September,,0,0,
2447,Identification of the zinc-binding protein specifically present in male rat liver as carbonic anhydrase III,"A zinc (Zn)-binding protein that is present specifically in the livers of male adult rats was detected by HPLC with in-line detection by mass spectrometry (ICP MS). The Zn-binding protein was purified on Sephadex G-75 and G3000SW HPLC columns, and was identified as carbonic anhydrase III (CAIII) based on the amino acid sequence of a peptide obtained on lysyl endopeptidase digestion. CAIII is expressed as one of the major Zn-binding proteins in the livers of male rats in an age-dependent manner, a comparable amount of Zn to that of copper, Zn-superoxide dismutase (Cu,Zn-SOD) being bound to CAIII at 8 weeks of age. Castration at 4 or 8 weeks of age was shown to reduce Zn bound to CAIII to 47.5% of the sham-operated control level, suggesting that the sex-dependent expression of CAIII is partly regulated by a sex hormone, androgen. The concentration of CAIII in the livers of Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease, was also estimated as Zn bound to CAIII and shown to be lower than that in Wistar rats before the onset of hepatitis. The concentration of CAIII was decreased specifically by repeated injections of cupric ions without the Cu,Zn-SOD concentration being affected. Copyright (C) 1999 Elsevier Science Ireland Ltd.",Carbonic anhydrase III;Copper;hpcl-icp ms;Sex-dependent expression;Speciation;Zinc-binding protein;amino acid sequence;animal experiment;animal tissue;article;controlled study;female;gene expression regulation;high performance liquid chromatography;liver metabolism;male;mass spectrometry;molecular weight;nonhuman;rat;ultrafiltration;carbonate dehydratase/ec [Endogenous Compound];carbonate dehydratase III/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];unclassified drug;zinc/ec [Endogenous Compound];zinc binding protein/ec [Endogenous Compound],"Suzuki, K. T.;Takenaka, J.;Ogra, Y.",1999,31 Oct,http://dx.doi.org/10.1016/S0009-2797%2899%2900122-2,0,0,
2448,Cerebral white matter involvement in Wilson's disease,"Although Wilson's disease (WD) involves primarily gray matter with the main target on the basal ganglia, white matter degeneration has been reported. From a review of the literature and our studies, cerebral white matter involvement occurred in 6-20% of patients with WD and mainly affected the frontal lobes. The majority of the patients were adolescents or young adults who usually had had the disease for several years. Patients were often not treated, poorly treated, or induced by d-penicillamine treatment. Clinical features were characterized by contralateral weakness, tremor and dystonia. Psychiatric symptoms, particularly schizophrenia-like psychosis, were common and might be the initial presentation. Epileptic seizures were also common and patients responded to antiepileptic and decoppering treatments. The long-term prognosis appeared to be favorable when the patients had regular and proper treatment.",Demyelination;Dystonia;Hepatolenticular degeneration;Psychosis;Seizure;Wilson's disease;adolescent;adult;clinical article;clinical feature;demyelination/di [Diagnosis];dystonia/di [Diagnosis];female;frontal lobe;human;male;patient compliance;prognosis;psychosis/di [Diagnosis];review;schizophrenia/di [Diagnosis];school child;seizure/di [Diagnosis];seizure/dt [Drug Therapy];white matter;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];anticonvulsive agent/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/to [Drug Toxicity],"Chu, N. S.;Huang, C. C.",1999,,,0,0,
2449,Management of chronic liver disease,"Childhood liver disorders have, in general, mode of presentations which are distinct from that in adult population. It is due to varying etiology and natural history of the liver diseases in childhood. Chronic hepatitis B and C can be managed with alpha interferon. Remission rates in children have been reported to be between 20-58%. Recently available lamuvidine has also been used in combination with interferon therapy. Oral chelation therapy and liver transplantation have radically affected the outcome of patients with Wilson's disease. Corticosteroids and immunosuppressive therapy are effective in reducing both morbidity and mortality due to auto-immune hepatitis. Offending carbohydrates are eliminated from the diet of patients with galactosemia and hereditary fructose intolerance. The most important and often neglected component of management of chronic liver diseases in childhood are nutritional management and prompt interventions for ascites, spontaneous bacterial peritonitis, portal hypertension and hepatic encephalopathy. With definitive etiological and histological assessment and institution of specific as well as supportive therapy, children with chronic liver disease can have a prolonged survival with improved quality of life. Several of them can potentially receive the liver transplant as and when it becomes available.",Chronic hepatitis;Chronic liver disease;Interferon;Liver transplantation;ascites/dt [Drug Therapy];autoimmune hepatitis/dt [Drug Therapy];child;chronic hepatitis/dt [Drug Therapy];chronic hepatitis/et [Etiology];chronic hepatitis/su [Surgery];chronic liver disease/dt [Drug Therapy];chronic liver disease/et [Etiology];chronic liver disease/su [Surgery];drug induced disease/si [Side Effect];esophagus varices bleeding/co [Complication];esophagus varices bleeding/th [Therapy];galactosemia/et [Etiology];galactosemia/th [Therapy];glycogen storage disease/et [Etiology];hepatic encephalopathy/co [Complication];hepatic encephalopathy/dt [Drug Therapy];hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];hereditary fructose intolerance/et [Etiology];hereditary fructose intolerance/th [Therapy];human;kidney failure/co [Complication];liver cell carcinoma/et [Etiology];liver cirrhosis/dt [Drug Therapy];liver disease/dt [Drug Therapy];liver disease/et [Etiology];malnutrition/th [Therapy];peritonitis/dt [Drug Therapy];portal hypertension/co [Complication];review;Wilson disease/dt [Drug Therapy];alpha interferon/ae [Adverse Drug Reaction];alpha interferon/cb [Drug Combination];alpha interferon/do [Drug Dose];alpha interferon/dt [Drug Therapy];alpha interferon/pd [Pharmacology];alpha interferon/sc [Subcutaneous Drug Administration];amantadine/cb [Drug Combination];amantadine/dt [Drug Therapy];amiloride/dt [Drug Therapy];antifibrotic agent/dt [Drug Therapy];antivirus agent/cb [Drug Combination];antivirus agent/dt [Drug Therapy];azathioprine/cb [Drug Combination];azathioprine/do [Drug Dose];azathioprine/dt [Drug Therapy];cefotaxime/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];ciprofloxacin/dt [Drug Therapy];colchicine/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];diuretic agent/ae [Adverse Drug Reaction];diuretic agent/do [Drug Dose];diuretic agent/dt [Drug Therapy];etacrynic acid/dt [Drug Therapy];furosemide/do [Drug Dose];furosemide/dt [Drug Therapy];glycyrrhizic acid/dt [Drug Therapy];immunosuppressive agent/cb [Drug Combination];immunosuppressive agent/do [Drug Dose];immunosuppressive agent/dt [Drug Therapy];lamivudine/cb [Drug Combination];lamivudine/dt [Drug Therapy];lufironil/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];prednisone/cb [Drug Combination];prednisone/do [Drug Dose];prednisone/dt [Drug Therapy];ribavirin/cb [Drug Combination];ribavirin/dt [Drug Therapy];spironolactone/ae [Adverse Drug Reaction];spironolactone/do [Drug Dose];spironolactone/dt [Drug Therapy];steroid/cb [Drug Combination];steroid/do [Drug Dose];steroid/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];thymosin alpha1/cb [Drug Combination];thymosin alpha1/dt [Drug Therapy];triamterene/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/do [Drug Dose];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];vasopressin/dt [Drug Therapy],"Thapa, B. R.",1999,,,0,0,
2450,Circling seizures in a case with Wilson's disease,"We report a case of Wilson's disease with circling seizures. Because of the existence of other types of frontal automatism and the EEG focus on the frontal regions, circling seizures of the patient were thought to originate from the frontal lobe. Magnetic resonance imaging demonstrated large cavitary lesions on bilateral frontal lobes. The mechanisms of circling behavior are discussed in association with Wilson's disease.","Epilepsy;Frontal Lobe;Seizures, Circling;Wilson's Disease;adolescent;article;case report;circling behavior;dysarthria;dystonia;electroencephalogram;human;male;priority journal;tonic clonic seizure/dt [Drug Therapy];tremor;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phenytoin/dt [Drug Therapy];pyridoxine/dt [Drug Therapy]","Saka, E.;Elibol, B.;Saygi, S.",1999,July,,0,0,
2451,CME questions,,DNA determination;Duchenne muscular dystrophy;dystonia;Friedreich ataxia;genetic disorder;multiple sclerosis;neurologic disease;note;priority journal;Wilson disease;ceruloplasmin/ec [Endogenous Compound];frataxin/ec [Endogenous Compound];penicillamine;tetrathiomolybdic acid;trientine;zinc,Anonymous,1999,,,0,0,
2452,Plasma exchange for hemolytic crisis in Wilson disease [4],,adolescent;case report;chelation;echography;hemolysis/di [Diagnosis];hemolysis/dt [Drug Therapy];hemolysis/th [Therapy];human;letter;male;plasmapheresis;priority journal;prothrombin time;slit lamp;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Matsumura, A.;Hiraishi, H.;Terano, A.",1999,07 Dec,,0,0,
2453,Generators of brain electrical activity in patients with Wilson's disease,"Electroencephalographic (EEG) generators were investigated in 13 patients suffering from hepatolenticular degeneration with and without neurological symptoms and in 13 healthy subjects for comparison by the use of FFT approximation. Quantitative assessment of motor deficits and psychiatric disturbances was correlated with EEG features. We found mainly an increase in delta activity, a decrease in alpha activity combined with a more posterior localisation of the EEG generators in the delta band and a more anterior one in the alpha band in patients compared with healthy controls. The localisation of the EEG generators in the patients with clinical apparent neurological symptoms were in all frequency bands more superficial compared with controls and patients without neurological symptoms. With longer duration of the disease, the lower the premorbid intelligence the more posterior was the delta EEG generator localised. Although the alpha EEG generator was more anteriorly localised with longer duration of the disease and more severe cognitive deficits, it was more superficial with more pronounced psychiatric symptoms, more severe cognitive deficits, lower premorbid intelligence and more pronounced motor disabilities. With more pronounced psychiatric symptoms and cognitive deficits, the beta EEG generator was more anteriorly localised. The present study demonstrated that a significant deviant EEG pattern exists between patients with and without clinical neurological symptoms and that stage-dependent alterations in psychiatric symptoms and cognitive ability are reflected on the EEG.",Dipole generators;eeg;Hepatolenticular degeneration;Wilson's disease;adult;alpha rhythm;article;clinical article;cognitive defect/di [Diagnosis];cognitive defect/et [Etiology];controlled study;delta rhythm;electroencephalogram;human;intelligence;mental disease/di [Diagnosis];mental disease/et [Etiology];motor dysfunction/di [Diagnosis];motor dysfunction/et [Etiology];priority journal;tissue distribution;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];metal/cb [Drug Combination];metal/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Dierks, T.;Kuhn, W.;Oberle, S.;Muller, T.;Maurer, K.",1999,February,http://dx.doi.org/10.1007/s004060050060,0,0,
2454,Menkes disease and Wilson disease: Two sides of the same copper coin: Part I: Menkes disease,,Intracellular copper transport;Kinky' hair disease;Menkes disease;Wilson disease;biochemistry;chromosome 13q;chromosome Xq;clinical feature;copper metabolism;degenerative disease/di [Diagnosis];degenerative disease/dt [Drug Therapy];disease classification;gene mutation;human;Menkes syndrome/di [Diagnosis];Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];molecular biology;oral drug administration;parenteral drug administration;pathology;priority journal;review;Wilson disease/di [Diagnosis];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper acetate/ad [Drug Administration];copper acetate/dt [Drug Therapy];copper chloride/ad [Drug Administration];copper chloride/cb [Drug Combination];copper chloride/do [Drug Dose];copper chloride/dt [Drug Therapy];copper sulfate/ad [Drug Administration];copper sulfate/dt [Drug Therapy];enzyme/ec [Endogenous Compound];gene product/ec [Endogenous Compound];histidine/cb [Drug Combination];histidine/do [Drug Dose];histidine/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy],"Menkes, J. H.",1999,,http://dx.doi.org/10.1016/S1090-3798%2899%2990048-X,0,0,
2455,Intracellular localization of the Menkes and Wilson's disease proteins and their role in intracellular copper transport,"Copper is a heavy metal ion essential for the activity of a variety of enzymes in the body. In excess, copper is a very toxic ion and therefore efficient regulation of its metabolism is required. This is dramatically illustrated by the genetic disorders X-linked Menkes disease and autosomal recessive Wilson's disease. In 1993, both the Menkes and Wilson's genes were isolated and it was found that these genes encode homologous cation copper transporting P-type ATPase proteins. The Menkes protein (ATP7A)is expressed in most tissues, except liver. In contrast, the Wilson's protein (ATP7B) is abundantly expressed in liver. Intracellular localization of those proteins was investigated. Both ATP7A and ATP7B are localized in the trans-Golgi network and post-Golgi vesicular compartment (PGVC) in the cell. This intracellular localization was altered by the copper content present in the cell. This result may support the hypothesis that ATP7A and ATP7B are involved in cellular copper transport and those proteins could be suitable models for elucidating intracellular copper metabolism.",atp7a;atp7b;Copper metabolism;Menkes disease;Post-Golgi vesicular compartment;Trans-Golgi network;Wilson disease;cellular distribution;clinical feature;gene isolation;Golgi complex;human;intracellular transport;Menkes syndrome/cn [Congenital Disorder];Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];priority journal;protein expression;protein localization;review;subcutaneous drug administration;tissue distribution;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper derivative/dt [Drug Therapy];histidine copper/dt [Drug Therapy];isoenzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];unclassified drug,"Suzuki, M.;Gitlin, J. D.",1999,,http://dx.doi.org/10.1046/j.1442-200x.1999.01090.x,0,0,
2456,Wilson's disease and Menkes disease,,animal model;biliary excretion;clinical feature;copper metabolism;editorial;gene expression;gene mutation;human;laboratory diagnosis;liver cirrhosis/et [Etiology];Menkes syndrome/cn [Congenital Disorder];Menkes syndrome/di [Diagnosis];Menkes syndrome/et [Etiology];priority journal;protein domain;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Aoki, T.",1999,,http://dx.doi.org/10.1046/j.1442-200x.1999.01111.x,0,0,
2457,Disorders of copper transport,"Copper is an essential component of a number of important enzymes. Efficient systems have developed for providing sufficient copper for essential functions, while eliminating excess to avoid tissue toxicity. Copper transport is disrupted in two human diseases: Wilson disease and Menkes disease. Both have defects in copper transporting membrane proteins. Many other proteins are involved in copper transport. Some of these proteins have been identified through a study of the similar copper pathway in yeast. This suggests other copper transport diseases are yet to be discovered. Molecular diagnosis holds promise for reliable diagnosis of patients. Testing of flanking markers is a reliable way to detect presymptomatic sibs of a definite patient. While most heavy metals are either too rare or too insoluble to be of biological importance, at least eleven appear to be essential for normal function. These include vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, selenium, molybdenum and tin<sup>1</sup>. Most of these metals, while essential for normal function, are toxic when present in excess. Little is known about the mechanisms of homeostatic control required to maintain the fine balance between necessity and toxicity. Cloning of genes in the copper transport pathway has led to our better understanding of the complexity of metal transport systems<sup>2</sup>.",cell transport;diagnosis;human;Menkes syndrome/et [Etiology];nonhuman;priority journal;review;toxicity;Wilson disease/et [Etiology];yeast;carrier protein/ec [Endogenous Compound];copper/ec [Endogenous Compound];enzyme/ec [Endogenous Compound];marker/ec [Endogenous Compound];membrane protein/ec [Endogenous Compound];protein/ec [Endogenous Compound],"Cox, D. W.",1999,,,0,0,
2458,Menkes disease and Wilson disease: Two sides of the same copper coin. Part II: Wilson disease,,Autosomal recessive disorders;Copper metabolism;Menkes disease;Wilson disease;autosomal recessive disorder;bone marrow suppression/si [Side Effect];clinical feature;gastrointestinal symptom/si [Side Effect];human;Menkes syndrome;pathogenesis;priority journal;rash/si [Side Effect];review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];iron binding protein/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Menkes, J. H.",1999,,,0,0,
2459,Penicillamine,,bone marrow depression/si [Side Effect];drug contraindication;fever/si [Side Effect];heavy metal poisoning/dt [Drug Therapy];human;kidney disease/si [Side Effect];liver disease/si [Side Effect];nausea/si [Side Effect];note;proteinuria/si [Side Effect];rash/si [Side Effect];urinary excretion;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];lead/to [Drug Toxicity];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pr [Pharmaceutics],Anonymous,1999,,,0,0,1029
2460,Drugs and toxins associated with myopathies,"Drug-induced muscle dysfunction represents a significant and perhaps increasing subset of neuromuscular disorders that face the clinician. Whereas severe symptoms of proximal weakness and elevated muscle enzymes in an uncomplicated patient taking a single medication may lead to straightforward diagnosis, the tendency for patients with multisystem disease, on multiple medications, with multiple potential causes for weakness makes the diagnosis of toxic myopathy challenging. Furthermore, many toxic myopathies are characterized by nonspecific clinical and laboratory findings, ultimately requiring a trial of drug discontinuation in order to clarify the diagnosis. This review summarizes recent observations with regard to toxic effects on neuromuscular transmission and toxic myopathies.",alcohol abuse;autoimmune disease/dt [Drug Therapy];autoimmune disease/et [Etiology];autoimmune disease/si [Side Effect];botulism/di [Diagnosis];botulism/dt [Drug Therapy];botulism/et [Etiology];comorbidity;drug combination;drug withdrawal;human;Human immunodeficiency virus infection/et [Etiology];leukemia/dt [Drug Therapy];malaria/dt [Drug Therapy];muscle weakness/et [Etiology];muscle weakness/si [Side Effect];myasthenia gravis/di [Diagnosis];myasthenia gravis/dt [Drug Therapy];myasthenia gravis/et [Etiology];myasthenia gravis/si [Side Effect];myopathy/di [Diagnosis];myopathy/et [Etiology];myopathy/si [Side Effect];neuromuscular disease/di [Diagnosis];neuromuscular disease/et [Etiology];neuromuscular disease/si [Side Effect];paralysis/si [Side Effect];preeclampsia/dt [Drug Therapy];priority journal;review;rheumatoid arthritis/dt [Drug Therapy];side effect;toxicity/si [Side Effect];Wilson disease/dt [Drug Therapy];alcohol/ae [Adverse Drug Reaction];alpha interferon/ae [Adverse Drug Reaction];alpha interferon/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];aminocaproic acid/ae [Adverse Drug Reaction];aminoglycoside antibiotic agent/ae [Adverse Drug Reaction];amiodarone/ae [Adverse Drug Reaction];antilipemic agent/ae [Adverse Drug Reaction];botulinum antiserum/ae [Adverse Drug Reaction];botulinum antiserum/dt [Drug Therapy];botulinum toxin/to [Drug Toxicity];chloroquine/ae [Adverse Drug Reaction];chloroquine/dt [Drug Therapy];clofibrate/ae [Adverse Drug Reaction];colchicine/ae [Adverse Drug Reaction];corticosteroid/ae [Adverse Drug Reaction];didanosine/ae [Adverse Drug Reaction];emetine/ae [Adverse Drug Reaction];etretinate/ae [Adverse Drug Reaction];germanium/ae [Adverse Drug Reaction];iodinated contrast medium/ae [Adverse Drug Reaction];magnesium/ae [Adverse Drug Reaction];magnesium/dt [Drug Therapy];mevinolin/ae [Adverse Drug Reaction];muscle enzyme/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];phenytoin/ae [Adverse Drug Reaction];pravastatin/ae [Adverse Drug Reaction];procainamide/ae [Adverse Drug Reaction];quinidine/ae [Adverse Drug Reaction];quinine/ae [Adverse Drug Reaction];streptokinase/dt [Drug Therapy];vecuronium derivative/ae [Adverse Drug Reaction];zidovudine/ae [Adverse Drug Reaction],"Pascuzzi, R. M.",1998,,http://dx.doi.org/10.1097/00002281-199811000-00003,0,0,
2461,Recovery of neurological deficits in a case of Wilson's disease after liver transplantation,,adult;case report;computer assisted tomography;conference paper;esophagus varices bleeding/co [Complication];esophagus varices bleeding/th [Therapy];human;liver transplantation;male;neurologic disease/co [Complication];nuclear magnetic resonance imaging;priority journal;sclerotherapy;Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];penicillamine,"Lui, C. C.;Chen, C. L.;Cheng, Y. F.;Lee, T. Y.",1998,,http://dx.doi.org/10.1016/S0041-1345%2898%2901048-3,0,0,
2462,Ophthalmologic effects of bowel disease,"Ocular findings in diseases affecting primarily the digestive tract are relatively rare; however, it is important for the physician to recognize these relationships, appropriately uncover symptoms related to the eye disease, and have the patient evaluated by an ophthalmologist if indicated. In addition, ocular inflammation may be the first indication of bowel disease (e.g., uveitis in Crohn's disease). This article describes the associations between ocular diseases and gastrointestinal diseases and their causes, signs, symptoms, prognosis, and treatment.",adenomatous polyp;Behcet disease/dt [Drug Therapy];Behcet disease/et [Etiology];cornea disease/di [Diagnosis];cornea disease/et [Etiology];Crohn disease;diet supplementation;disease association;enteropathy/di [Diagnosis];enteropathy/et [Etiology];episcleritis/di [Diagnosis];episcleritis/dt [Drug Therapy];episcleritis/th [Therapy];eye disease/co [Complication];eye disease/dt [Drug Therapy];eye disease/et [Etiology];human;intestine lipodystrophy/dt [Drug Therapy];intestine lipodystrophy/et [Etiology];liver failure;primary biliary cirrhosis;prognosis;pseudoxanthoma elasticum;recurrent disease;review;scleritis/di [Diagnosis];scleritis/dt [Drug Therapy];scleritis/et [Etiology];scleritis/th [Therapy];Sjoegren syndrome/co [Complication];symptom;ulcerative colitis/et [Etiology];uveitis/di [Diagnosis];uveitis/dt [Drug Therapy];uveitis/et [Etiology];Wilson disease;xerophthalmia/co [Complication];xerophthalmia/th [Therapy];antibiotic agent/dt [Drug Therapy];colchicine/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];nonsteroid antiinflammatory agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];steroid/dt [Drug Therapy];vitamin,"Nakla, M. L.;Heffler, K. F.",1998,,http://dx.doi.org/10.1016/S0889-8553%2805%2970027-3,0,0,
2463,"Zinc deficiency can cause depression, hair loss and oligospermia. [German]",,depression/et [Etiology];hair loss/et [Etiology];human;malnutrition/et [Etiology];oligospermia/et [Etiology];physiology;short survey;Wilson disease/et [Etiology];zinc deficiency/di [Diagnosis];zinc deficiency/dt [Drug Therapy];zinc deficiency/et [Etiology];zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Pannewig, K.",1998,30 Aug,,0,0,
2464,"Maximum tolerated dose and repeated dose toxicity studies of triethylenetetramine dihydrochloride, a copper chelating agent, by oral administration to beagle dogs","Triethylenetetramine dihydrochloride (trientine-2HCl), a copper chelating agent used to treat Wilson's disease, was tested for maximum tolerated dose and, subacute and chronic toxicity in beagle dogs. 1) Maximum tolerated dose study. One male and one female beagle dogs received trientine- 2HCl by oral administration of variable dosages (50 to 2000 mg/kg) or at constant dosages of 200 or 600 mg/kg/day for two weeks. After one administration at 2000 or 1000 mg/kg severe signs (abnormal gait, ataxia, emesis, diarrhoea, body tremor) and marked bodyweight loss were evident. In the constant dosage phase similar effects of treatment were apparent in both animals receiving 600 mg/kg/day. The approximate lethal dose was considered to be more than 2000 mg/kg. 2) Four week study. Beagle dogs received trientine-2HCl orally at dosages of 50, 125 of 300 mg/kg/day for 4 weeks followed by a 4-week reversibility phase. There were no deaths. For some animals receiving 300 mg/kg/day, during the last week of treatment underactivity, abnormal gait, ataxia and body tremor were observed. In the lungs, interstitial pneumonia was recorded for one control male and four animals that received 300 mg/kg/day with or without recovery. Toxicokinetic analysis revealed that exposure of the animals to trientine-2HCl was dosage- dependent and that no significant accumulation of trientine-2HCl occurred during the dosing period. 3) Twenty-six week study. Beagle dogs were scheduled to receive trientine-2HCl orally at dosages of 50, 100 or 200 mg/kg/day for 26 weeks followed by a 13-week reversibility phase. However, in view of the severe signs which resulted in the sacrifice for humane reasons of two males and one female receiving 200 mg/kg/day during week 9 of treatment, surviving dogs of this group were only treated for 10 weeks. Signs before despatch included marked underactivity, body tremors, abnormal gait, limited use of limb and prone posture. The ante mortem neurological examination generally indicated depressed postural and flexor withdrawal reactions. The signs were rapidly reversible except in the one female which was killed humanely on day 2 of the reversibility period. Abnormal 'stiff legged' gait and underactivity were evident, from week 23 of treatment, in two males and one female receiving 100 mg/kg/day. In the absence of any macroscopic or histopathologic findings, even after the examination of additional samples of muscle and nerve, the exact nature of this condition could not be elucidated. In all treated groups low copper and zinc concentrations in the livers and high urinary copper and zinc concentrations were found. The NOAEL was considered to be 50 mg/kg/day.",Ataxia;Copper chelating agent;Dog;General toxicity;Triethylenetetramine dihychloride;Wilson's disease;animal experiment;animal model;article;chronic toxicity;controlled study;copper metabolism;fluid intake;histopathology;maximum permissible dose;nonhuman;oral drug administration;toxicity testing;toxicokinetics;Wilson disease;chelating agent/ad [Drug Administration];chelating agent/do [Drug Dose];chelating agent/to [Drug Toxicity];chelating agent/pd [Pharmacology];trientine/ad [Drug Administration];trientine/do [Drug Dose];trientine/to [Drug Toxicity];trientine/pd [Pharmacology],"Maemura, S.;Matsuzaki, Y.;Asano, T.;Minematsu, S.;Yanagisawa, T.;Iijima, O. T.;Sasaki, H.;East, P. W.;Creasy, D. M.;Virgo, D. M.",1998,,,0,0,
2465,A critical evaluation of copper metabolism in Indian Wilson's disease children with special reference to their phenotypes and relatives,"Wilson's disease is an autosomal recessive disorder of copper accumulation in various organs, with most common clinical manifestations such as hepatic, neurological, and renal dysfunctions. Serum copper and ceruloplasmin in Wilson's disease were significantly lower as compared to normals, controls, and relatives of Wilson's disease patients, whereas marked hypercupriuria (145 +/- 7 mug/24 h) was observed in Wilson's children only. A good correlation (r = 0.92) was found between non-ceruloplasmin-bound copper and 24-h urinary copper excretion in Wilson's disease patients. Further, copper studies among the different phenotypes of Wilson's disease revealed substantially low serum ceruloplasmin and a marked hypercupriuria in Wilson's disease children associated with renal tubular acidosis as compared to the patients with either hepatological or neurological manifestations. Serum ceruloplasmin levels in 14 patients of Wilson's disease were between 14 and 20 mg/dL. These patients of Wilson's disease were confirmed by measuring liver biopsy copper, which was about nine times higher than normal hepatic copper content. During the family screening by copper studies, four asymptomatic siblings were diagnosed for Wilson's disease. These subjects were then started on D-penicillamine therapy because presymptomatic treatment prevents progression of the disease complications.",Copper metabolism;Family screening;Hepatic copper;Phenotypes;Wilson's disease;adolescent;article;child;childhood disease;controlled study;female;human;liver biopsy;major clinical study;male;phenotype;relative;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Prasad, R.;Kaur, G.;Walia, B. N. S.",1998,,,0,0,
2466,Copper and boron as examples of dietary trace elements important in bone development and disease,"Boron and copper are examples of elements that are present in man in small or 'trace,' but important amounts. Copper is essential for bone growth and development, and copper supplementation reduces bone loss in middle-aged women. Copper deficiency is indicated by the presence of long bone abnormalities (osteopenia, fraying and cupping of the provisional zone of calcification, metaphysial spurs, fractures), psychomotor retardation, hypotonia, hypopigmentation, prominent scalp veins in palpable periosteal depressions, pallor, sideroblastic anemia resistant to iron treatment, vacuolated erythroid and myeloid cells in bone marrow with iron deposition in the vacuoles and some mitochondria, hepatosplenomegaly, neutropenia (<1.0 x 10<sup>9</sup>/L), and serum copper and ceruloplasmin concentrations below 6.28 mmol/L and 0.13 g/L, respectively. Unintentional copper depletion by overzealous zinc therapy or chelation therapy (eg, deferoxamine or EDTA) as treatment for heavy metal poisoning, vascular disease, or intermittent claudication is of obvious importance. Intentional copper chelation with drugs including penicillamine for treatment of abnormalities including Wilson's disease, Parkinson's disease, and familial amyotrophic lateral sclerosis may also deplete copper stores. Signs of copper deficiency associated with perinatal stress are sometimes confused with unexplained fractures in infant nonaccidental injury that are sometimes manifest in the battered child syndrome. Boron is beneficial for mineral, vitamin D, insulin, and energy substrate metabolism and immune function in animals and humans. In particular, dietary boron has physiological effects beneficial to bone growth and maintenance. Further characterization of the metabolic roles of these and other trace elements related to bone metabolism seems an extremely prudent endeavor because of the probable association of several refractory bone diseases with trace and ultra-trace elements nutriture.",article;bone atrophy;bone development;bone disease/th [Therapy];bone growth;clinical feature;copper deficiency;dietary intake;differential diagnosis;drug effect;fracture;human;osteopenia;priority journal;vascular disease;boron;chelating agent;copper;deferoxamine;edetic acid;trace element;vitamin D;zinc,"Hunt, C. D.",1998,,http://dx.doi.org/10.1097/00001433-199810000-00006,0,0,
2467,Early and severe neurological features in a Wilson disease patient compound heterozygous for two frameshift mutations,"We describe a patient with Wilson disease who presented at 11 years of age with neurological symptoms and subsequent rapid progression of neurological impairment but absent hepatic manifestations. Molecular analysis showed compound heterozygosity for two frameshift mutations, 2299insC and 214delAT, which most likely result in an absent or inactive protein product. Mutation-phenotypic analysis indicates that this genotype does not explain the severe phenotype, suggesting the presence of modifying factors. Conclusion: Wilson disease may present even in childhood or adolescence with neurological abnormalities in the absence of hepatic manifestations.",Molecular pathology;Neurological features;Wilson disease;article;case report;female;frameshift mutation;genetic analysis;genotype;heterozygosity;human;liver biopsy;liver function test;neurologic disease/co [Complication];neurologic disease/cn [Congenital Disorder];phenotype;priority journal;school child;sequence analysis;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Angius, A.;Dessi, V.;Lovicu, M.;De Virgiliis, S.;Pirastu, M.;Cao, A.;Antonio, C.",1998,,http://dx.doi.org/10.1007/s004310050783,0,0,
2468,Copper: Another great unknown?. [Spanish],,child;childhood disease/di [Diagnosis];childhood disease/dt [Drug Therapy];childhood disease/et [Etiology];copper metabolism;human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];Menkes syndrome/di [Diagnosis];Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];neurological complication/co [Complication];review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Sanchez, C. S.",1998,,,0,0,
2469,"Neuropsychiatric correlates and treatment of lenticulostriatal diseases: A review of the literature and overview of research opportunities in Huntington's, Wilson's, and Fahr's diseases. A report of the ANPA Committee on Research","This report reviews clinical neuropsychiatric findings and opportunities for research in Huntington's, Wilson's, and Fahr's diseases. Consistent, systematic methodology is lacking among neuropsychiatric studies in these lenticulostriatal diseases. Systematic cross-sectional and longitudinal assessments are needed to ascertain the prevalence of psychiatric disorders as a function of disease course. Preliminary synthesis of existing data suggests the following heuristic relationships in these diseases: depression with parkinsonian states; personality changes with caudate or putamen disease; psychosis, impulsivity, and sexual disorders with caudate disease; dementia and mania with caudate and pallidal diseases; and compulsions with pallidal disease. Correlation of neuropsychiatric findings with disease stage, clinical signs, and radiologic, metabolic, physiologic, and pathologic markers of disease will add to our understanding of these conditions.",birth defect/si [Side Effect];brain disease/di [Diagnosis];brain disease/dt [Drug Therapy];brain disease/et [Etiology];brain disease/th [Therapy];cerebral palsy/si [Side Effect];clinical feature;corpus striatum;craniofacial malformation/si [Side Effect];depression/di [Diagnosis];depression/dt [Drug Therapy];depression/et [Etiology];depression/th [Therapy];disease association;disease course;disease severity;extrapyramidal symptom/si [Side Effect];Fahr disease/di [Diagnosis];Fahr disease/dt [Drug Therapy];Fahr disease/et [Etiology];Fahr disease/th [Therapy];globus pallidus;human;Huntington chorea/di [Diagnosis];Huntington chorea/dt [Drug Therapy];Huntington chorea/et [Etiology];Huntington chorea/th [Therapy];hydrocephalus/si [Side Effect];impulsiveness;longitudinal study;metabolism;methodology;neuroleptic malignant syndrome/dt [Drug Therapy];neuroleptic malignant syndrome/si [Side Effect];neuropathology;neuropsychiatry;parkinsonism;personality disorder/di [Diagnosis];personality disorder/dt [Drug Therapy];personality disorder/et [Etiology];personality disorder/th [Therapy];physiology;priority journal;psychosis/di [Diagnosis];psychosis/dt [Drug Therapy];psychosis/et [Etiology];psychosis/th [Therapy];putamen;radiodiagnosis;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alpha tocopherol/dt [Drug Therapy];apomorphine/ct [Clinical Trial];apomorphine/dt [Drug Therapy];ascorbic acid/dt [Drug Therapy];baclofen/ct [Clinical Trial];baclofen/dt [Drug Therapy];bromocriptine/dt [Drug Therapy];buspirone/ct [Clinical Trial];buspirone/dt [Drug Therapy];cannabidiol/ct [Clinical Trial];cannabidiol/dt [Drug Therapy];clozapine/ct [Clinical Trial];clozapine/dt [Drug Therapy];dantrolene/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];fluoxetine/ct [Clinical Trial];fluoxetine/dt [Drug Therapy];haloperidol/ct [Clinical Trial];haloperidol/dt [Drug Therapy];idebenone/ct [Clinical Trial];idebenone/dt [Drug Therapy];ketamine/ct [Clinical Trial];ketamine/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];thiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];ubidecarenone/ct [Clinical Trial];ubidecarenone/dt [Drug Therapy];zinc/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Lauterbach, E. C.;Cummings, J. L.;Duffy, J.;Coffey, C. E.;Kaufer, D.;Lovell, M.;Malloy, P.;Reeve, A.;Royall, D. R.;Rummans, T. A.;Salloway, S. P.",1998,Summer,,0,0,
2470,Trace elements in human health and disease: An update,,cognition;developing country;editorial;growth retardation/et [Etiology];health status;human;infantile diarrhea/dt [Drug Therapy];infection/et [Etiology];priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];zinc deficiency/ep [Epidemiology];trace element/dt [Drug Therapy];trace element/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Prasad, A. S.",1998,,http://dx.doi.org/10.1002/%28SICI%291520-670X%281998%2911:2/3%3C61::AID-JTRA1%3E3.0.CO;2-7,0,0,
2471,Targeting of tetrathiomolybdate on the copper accumulating in the liver of LEC rats,"The uptake of tetrathiomolybdate (TTM) by the liver and the removal of copper (Cu) accumulating in the liver in a form bound to metallothionein (MT) by TTM were studied in Long-Evans cinnamon (LEC) rats, an animal model of Wilson disease, in order to develop better treatments for the disease and Cu toxicity. Although molybdenum (Mo) was incorporated in a dose-dependent manner into the livers of both LEC and Long-Evans agouti (LEA) rats, the original strain of LEC rats used as a reference animal, the uptake into the liver of LEC rats was 13 times higher than that in LEA rats. The concentration of Mo in the soluble fraction plateaued and it was distributed more in the insoluble fraction with a higher dose in LEC rats. The concentration of Cu in the whole livers of LEC rats was decreased by TTM in a dose-dependent manner only at lower doses. However, the concentration of Cu in the soluble fraction continued to decrease with the dose of TTM. The results can be explained in terms of complex formation. Namely, TTM forms a complex with Cu, tentatively referred to a Cu/TTM complex, that can be effluxed into the bloodstream, and then binds selectively to albumin when the dose of TTM is low. On the other hand, TTM forms an insoluble complex, named as a Cu/TTM polymer that is precipitated in the liver when the dose is high. The results further indicate that TTM taken up by a cell is immobilized in the celt through the dose-dependent formation of a complex containing Cu, Mo and sulfur (S), which causes further uptake of TTM. TTM injected into rats or incubated in vitro with serum does not remove Cu from ceruloplasmin. TTM is, thus, suggested to target a cell accumulating excess Cu as Cu-MT, and to remove Cu selectively without interacting with Cu in Cu-enzymes. The results indicate that TTM is taken up by the liver depending on the amount of Cu accumulating in the form of MT, and then Cu is effluxed together with Mo in the form of Cu/TTM complex into the bloodstream.",Ceruloplasmin;icp-ms;LEC rats;Metallothionein;Tetrathiomolybdate;animal cell;animal experiment;animal model;animal tissue;article;chromosome 16;gene expression;high performance liquid chromatography;mass spectrometry;nonhuman;protein analysis;protein binding;protein synthesis;rat;statistical analysis;Wilson disease;copper;tetrathiomolybdic acid,"Ogra, Y.;Suzuki, K. T.",1998,April,http://dx.doi.org/10.1016/S0162-0134%2898%2900012-9,0,0,
2472,Zinc in human health: An update,"In this review topics such as zinc and growth, zinc and serum testosterone levels, association of zinc and iron deficiencies, zinc and Alzheimer's disease, zinc as a therapeutic agent, and role of zinc in immunity, have been covered. A meta-analysis of zinc supplementation trials from nine countries in Latin America and the Caribbean, eight from North America or Europe, five from Asia and the Middle East, and three from Africa revealed a highly significant effect of zinc supplementation on height and weight in children less than 13 years of age. It appears that the growth stimulating effect of zinc is mediated through changes in circulating IGF-1. A recent study from China showed that zinc supplementation improved neuropsychological functions in children 6 to 9 years old. A study from Birmingham, Alabama showed that zinc-supplemented women gave birth to infants who weighed more and had greater head circumference in comparison to infants of women who did not receive zinc. Serum testosterone correlated with cellular zinc concentration in healthy adults ages 20 to 80 years of age. Therapeutic uses of zinc include treatment of infantile diarrhea and chronic diarrhea in developing countries, treatment of common cold, and treatment of Wilson's disease. Recent studies indicated that in humans zinc deficiency results in an imbalance between TH1 and TH2 cell functions, which accounts for decreased cell-mediated immunity. Zinc is a T cell-specific growth factor, and a decreased gene expression of DNA-synthesizing enzyme thymidine kinase in zinc-deficient HUT-78 - a malignant lymphoblastoid human T cell line - adversely affected the DNA synthesis in S phase and delayed cell cycle.",igf-1;Testosterone;th1;th2;Tk;Zinc;Alzheimer disease/dt [Drug Therapy];article;body height;body weight;cell cycle S phase;cellular immunity;child health;chronic diarrhea/dt [Drug Therapy];common cold/dt [Drug Therapy];developing country;diet supplementation;DNA synthesis;head circumference;human;infantile diarrhea/dt [Drug Therapy];iron deficiency;neuropsychology;pregnancy;priority journal;testosterone blood level;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];zinc deficiency/dt [Drug Therapy];somatomedin/ec [Endogenous Compound];testosterone/ec [Endogenous Compound];thymidine kinase/ec [Endogenous Compound];zinc/dt [Drug Therapy];zinc/ec [Endogenous Compound],"Prasad, A. S.",1998,,http://dx.doi.org/10.1002/%28SICI%291520-670X%281998%2911:2/3%3C63::AID-JTRA2%3E3.0.CO;2-5,0,0,
2473,Concurrent administration of D-penicillamine and zinc has no advantages over the use of either single agent on copper excretion in the rat,"The present study was conducted to examine in rats whether the combined use of D-penicillamine (DPA) and a zinc salt, or the administration of a DPA/Zn complex could have some advantages over the use of either single agent on the excretion of copper. In a first experiment, three groups of adult male Sprague-Dawley rats were given by gavage one of the following treatments for 5 days: 0.5 mmol/kg/day of DPA, 0.046 mmol/kg/day of zinc acetate dihydrate, and 0.5 mmol/kg/day of DPA plus 0.046 mmol/kg/day of zinc acetate dihydrate. A fourth group of rats (control group) received deionized water during the same period. An increase in the urinary excretion of copper was observed following DPA treatment, which continued for at least 5 days after the administration of this compound was stopped. The amount of copper present in the feces, including that in the diet, was approximately 60 times greater than that normally present in control urines. During the period of zinc acetate administration, the amount of copper in the feces was slightly, but significantly greater than that during control, D-penicillamine, or D- penicillamine plus zinc acetate administration. No differences between the treated groups and the control group were found in brain, liver, kidney and spleen concentrations of rats 5 days after the end of the treatment period. In a second experiment, a similar comparison between D-penicillamine and sodium bis(3-mercapto-D-valinato)zinc hexahydrate (Na<inf>2</inf>[Zn(DPA)<inf>2</inf>]6H<inf>2</inf>O), both given by gavage, also showed no significant differences in the urinary excretion of copper in rats.",Copper excretion;D-Penicillamine;Tissue copper distribution;Zinc acetate;animal experiment;animal model;article;controlled study;copper metabolism;feces;male;nonhuman;oral drug administration;priority journal;rat;urinary excretion;Wilson disease;chelating agent/cb [Drug Combination];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];sodium bis(3 mercapto dextro valinato) zinc hexahydrate/cb [Drug Combination];unclassified drug;zinc acetate dihydrate/cb [Drug Combination];zinc derivative/cb [Drug Combination],"Domingo, J. L.;Gomez, M.;Jones, M. M.",1998,03 Apr,http://dx.doi.org/10.1016/S0300-483X%2898%2900017-1,0,0,
2474,Wilson's disease - A case report and review of literature,"We describe an 11 year old boy with signs and symptoms of cirrhosis of liver. He had a low ceruloplasmin level with elevated urinary copper excretion. The diagnosis of Wilson's disease was confirmed with liver biopsy which demonstrated mixed macro-and micronodular cirrhosis with copper deposition in hepatocytes and phagocytes. He was started on pencillamine therapy with excellent response. Over a period of 20 year follow-up he has manifested psychiatric disturbances, primarily during the time he was non- complaint with therapy. Currently he is back on pencillamine treatment and is doing well.",Ceruloplasmin;Cirrhosis;Copper;Wilson's disease;article;case report;child;clinical feature;copper metabolism;diagnostic approach route;disease course;human;liver cirrhosis/di [Diagnosis];male;neurologic examination;symptomatology;treatment planning;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Bashir, S.;Nawaz, A.;Mir, T.;Khan, F. A.",1998,,,0,0,
2475,"Wilson's disease - Clinical presentation, diagnosis and treatment. [German]","Wilson's disease is predominantly a disease of adolescents and young adults. Hepatic and/or neurologic symptoms characterize the clinical manifestation. Diagnostic procedures include determination of total serum copper, free serum copper, and serum ceruloplasmin concentrations as well as urinary copper excretion. The diagnosis can be confirmed by liver biopsy and histological examination as well as by determination of hepatic copper concentration. Patients require lifelong treatment with either a chelating agent, D-penicillamine or trientine, or zinc. Consequent therapy results in improvement of clinical symptoms, normalization of serum parameters of copper metabolism, and life expectancy comes close to that of the normal population. End-stage cirrhosis of the liver or fulminant hepatic failure requires liver transplantation. With this procedure the genetic defect can phenotypically be cured. Whether severe neurological disorders may also be improved, is not clear until today.",Copper metabolism;D-penicillamine;Liver transplantation;Wilson's disease;Zinc;ceruloplasmin blood level;clinical feature;copper blood level;life expectancy;neurologic disease/co [Complication];phenotype;review;Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Smolarek, C.;Stremmel, W.",1998,,,0,0,
2476,Subacute and chronic toxicity studies of triethylenetetramine dihydrochloride (TJA-250) by oral administration to F-344 rats,"Triethylenetetramine dihydrochloride (trientine-2HCl, TJA-250), a copper chelating agent used to treat Wilson's disease, was administered orally to male and female F-344 rats for 4 or 8 weeks at dosages of 0, 100, 350 or 1200 mg/kg/day or for 26 weeks at dosages of 50, 175 or 600 mg/kg/day. 4 or 8- week study. Two males receiving 1200 mg/kg/day died during week 8 of treatment. In males receiving 1200 mg/kg/day during weeks 5 to 8 of treatment, body weight gain and food consumption were decreased and hunched posture and thin build were observed. During week 4 or 8 of treatment urinalysis revealed, for males receiving 100 mg/kg/day or animals receiving 350 mg/kg/day or more, increased electrolyte outputs possibly due to the hydrochloride nature of trientine-2HCl, with low plasma alkaline phosphatase activities evident in animals receiving 350 or 1200 mg/kg/day. After 4 and 8 weeks, and during 8 weeks of treatment, high lung weights and bronchiolar epithelium hypertrophy and broncho-alveolar pneumonia were recorded for animals receiving 1200 mg/kg/day, and submucosal acute inflammation within the glandular region of the stomach was recorded for males receiving 350 or 1200 mg/kg/day and in all treated female groups. 26-week study. One male receiving 175 mg/kg/day and three males receiving 600 mg/kg/day died, showing lung changes. The body weight gain of animals receiving 600 mg/kg/day was slightly decreased. Blood chemistry and urinalysis examinations showed changes similar to those indicated in the 4- or 8-week study. The low plasma copper concentrations seen in males receiving 600 mg/kg/day, the slightly low liver copper concentrations found in animals receiving 600 or 175 mg/kg/day and the high urinary copper concentrations found in all treated groups, are attributed to the pharmacological action of trientine-2HCl. Histopathology revealed a dosage-related incidence and severity of focal chronic interstitial pneumonitis accompanied by fibrosis of the alveolar walls in females receiving 175 mg/kg/day or more and all treated male groups, but no significant pathological changes in the stomach. Apart from the histological changes found in the lung, all the above changes were reversible. In conclusion, the NOAEL of trientine-2HCl in this 26-week study was considered to be 50 mg/kg/day for females and less than 50 mg/kg/day for males.",Copper chelating agent;Interstitial pneumonitis;Rat;Repeated dose toxicity;Triethylenetetramine dihydrochloride;Wilson's disease;animal experiment;animal tissue;article;blood chemistry;chronic toxicity;enzyme activity;female;histopathology;interstitial pneumonia/di [Diagnosis];male;nonhuman;oral drug administration;toxicity;urinalysis;Wilson disease;alkaline phosphatase/ec [Endogenous Compound];chelating agent/ad [Drug Administration];chelating agent/do [Drug Dose];chelating agent/to [Drug Toxicity];copper/ec [Endogenous Compound];electrolyte/ec [Endogenous Compound];tja 250;trientine/ad [Drug Administration];trientine/do [Drug Dose];trientine/to [Drug Toxicity];unclassified drug,"Yanagisawa, T.;Maemura, S.;Sasaki, H.;Endo, T.;Okada, M.;East, P. W.;Virgo, D. M.;Creasy, D. M.",1998,October,,0,0,
2477,A case of neurologic type of Wilson's disease with increased aluminum in liver: Comparative study with histological findings to metal contents in the liver. [Japanese],"Histological findings and metal contents in the liver were studied in a patient with neurologic type of Wilson's disease. Copper and aluminum contents in the biopsied liver of the patient with Wilson's disease were measured simultaneously by neutron activation analysis at Research Reactor Institute, Kyoto University. Four cases of adult cirrhosis were selected as the control for cirrhosis and five cases of adult liver as the control for neurologically normal. The biopsied liver showed markedly increase in the copper content (814.4 mug/g: dry weight) and extremely high content of aluminum (479.4 mug/g: dry weight), compared to those of the controls. On the other hand, macroscopically no cirrhosis was observed and the characteristic appearances of macronodular cirrhosis failed to detect histologically. Interestingly the fibrosis or inflammation of the liver was seen faintly. It is likely that toxic metals in the liver such as aluminum, copper and manganese might be implicated in the pathogenesis of neurologic type of Wilson's disease.",Aluminum;Copper;Liver;Pathology;Wilson's disease;adult;article;brain atrophy/di [Diagnosis];case report;central nervous system disease/di [Diagnosis];central nervous system disease/dt [Drug Therapy];central nervous system disease/et [Etiology];controlled study;histology;human;human tissue;liver biopsy;liver cirrhosis/di [Diagnosis];liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/et [Etiology];male;neurologic disease/di [Diagnosis];neurologic disease/dt [Drug Therapy];neurologic disease/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];anticonvulsive agent/dt [Drug Therapy];ceruloplasmin;clonazepam/dt [Drug Therapy];manganese;penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];valproic acid/dt [Drug Therapy],"Yasui, M.;Kohmoto, J.;Ota, K.;Shinmen, K.;Tanaka, H.;Nogami, H.",1998,August,,0,0,
2478,Pregnancy in a patient treatd with trientine dihydrochloride for Wilson's disease. [French],,adult;case report;drug effect;female;human;note;pregnancy;treatment outcome;Wilson disease/dt [Drug Therapy];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology],"Desbriere, R.;Roquelaure, B.;Sarles, J.;Boubli, L.",1998,09 May,,0,0,
2479,Determination of trace elements in organs and tissues of zinc deficient mice by instrumental neutron activation analysis,"Six elements in several organs of mice fed with Zn deficient diet (Zn- def. mice) and those fed with control diet (control mice) were analyzed by INAA. Zinc concentrations in the organs of Zn-def. mice were not distinctly lower than those of control mice except for bone and pancreas. However, Co content increased significantly in all organs of Zn-def. mice compared with control mice, indicating the partial substitution of Co with Zn in metal proteins or other materials for the Zn-def. mice.",analytic method;animal experiment;animal model;article;controlled study;drug determination;mouse;neutron activation analysis;nonhuman;skin injury;Wilson disease;zinc deficiency;trace element;zinc,"Yanaga, M.;Iwama, M.;Takiguchi, K.;Noguchi, M.;Omori, T.",1998,,http://dx.doi.org/10.1007/BF02388031,0,0,
2480,Wilsons disease - Neurologic manifestations,"Wilsons disease (hepatolenticular degeneration) is a rare disease inherited as an autosomal recessive trait and due to a defect in the copper metabolism, characterized by plasma ceruloplasmin deficiency and excessive accumulation of copper in the liver, cornea, kidneys, and basal ganglia of the brain. In 40% to 50% of patients, the first manifestations of Wilsons disease are neurologic symptoms. Neurologic manifestations include any combination of tremor, dystonia, dysarthria, dysphagia, drooling, open-mouthedness and incoordination. The first sign may also be an inappropriate behavior. The treatment of patients with neurologic manifestations includes diet, pharmacologic therapy, and liver transplantation in selected patients.",Neurologic manifestations;Wilsons disease;autosomal recessive inheritance;basal ganglion;behavior disorder;ceruloplasmin blood level;copper deficiency;copper metabolism;cornea;diet therapy;dose response;drug accumulation;drug mechanism;dysarthria;dysphagia;dystonia;human;kidney;liver;liver transplantation;mental disease/si [Side Effect];neurologic disease/dt [Drug Therapy];neurologic disease/si [Side Effect];population research;protein deficiency;review;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/ae [Adverse Drug Reaction];chelating agent/ad [Drug Administration];chelating agent/cm [Drug Comparison];chelating agent/do [Drug Dose];chelating agent/dt [Drug Therapy];chelating agent/po [Oral Drug Administration];chelating agent/pk [Pharmacokinetics];chelating agent/pd [Pharmacology];copper/ec [Endogenous Compound];lithium/dt [Drug Therapy];mianserin/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];penicillamine/cm [Drug Comparison];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/po [Oral Drug Administration];penicillamine/pd [Pharmacology];prazolamine/do [Drug Dose];prazolamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];tricyclic antidepressant agent/dt [Drug Therapy];trientine/cm [Drug Comparison];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];unclassified drug;zinc derivative/do [Drug Dose];zinc derivative/dt [Drug Therapy];zinc derivative/pk [Pharmacokinetics];zinc derivative/pd [Pharmacology],"Matek, P.;Strinic, D.;Dorosulic, Z.;Maras, A.;Mihanovic, M.;Sucic, Z.",1998,,,0,0,
2481,"Metal (molybdenum, copper) accumulation and retention in brain, pituitary and other organs of ammonium tetrathiomolybdate-treated sheep","Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTM-treated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3.4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, testes and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0.02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0.02) and retained in the cerebellum and medulla oblongata in the TTM-treated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a strongly positive correlation (r 0.7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification.",Copper;Molybdenum;Tetrathiomolybdate;Toxicity;adrenal gland;animal experiment;animal model;animal tissue;article;bioaccumulation;brain;cerebellum;controlled study;correlation function;female;heart;hypophysis;kidney;liver;male;medulla oblongata;muscle;nonhuman;ovary;sheep;subcutaneous drug administration;testis;time;copper/ec [Endogenous Compound];metal;molybdenum/ec [Endogenous Compound];tetrathiomolybdate ammonium,"Haywood, S.;Dincer, Z.;Holding, J.;Parry, N. M.",1998,April,http://dx.doi.org/10.1079/BJN19980056,0,0,
2482,"Wilson disease in 1998: Genetic, diagnostic and therapeutic aspects",,chromosome 13q;chronic active hepatitis;clinical feature;gene mutation;human;liver biopsy;liver failure/su [Surgery];liver transplantation;long term care;oral drug administration;pathogenesis;priority journal;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];complementary DNA/ec [Endogenous Compound];copper/ec [Endogenous Compound];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];thiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Gollan, J. L.",1998,,,0,0,
2483,Wilson's disease: The scourge of copper,,chronic hepatitis/co [Complication];diet therapy;endocrine disease/co [Complication];eye disease;hemolysis/co [Complication];human;kidney disease/co [Complication];liver failure/co [Complication];liver transplantation;neurologic disease;onset age;oral drug administration;priority journal;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];copper;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Gitlin, N.",1998,April,http://dx.doi.org/10.1016/S0168-8278%2898%2980302-4,0,0,
2484,A case of systemic pseudo-pseudoxanthoma elasticum with diverse symptomatology caused by long term penicillamine use,"A 47 year old man presented with a two year history of increasing cervical dysphagia, dyspnoea, and cutaneous signs. He had been diagnosed 27 years previously with Wilson's disease and was treated with penicillamine (1.5 g daily). Systemic abnormality of elastic fibres was confirmed by light and electron microscopy following biopsy of skin, lung, oesophageal muscle, gum, pharyngeal tissue, and cervical connective tissue. Dysphagia was relieved by cricopharyngeal myotomy. Substitution of trientene dihydrochloride for penicillamine relieved cutaneous and systemic manifestations. This is possibly the first case demonstrating an association between prolonged penicillamine use and biopsy proved systemic pseudo-pseudoxanthoma elasticum. The presenting symptoms may have resulted from the abnormal numbers and properties of elastic fibres, and the changes were caused by penicillamine use, rather than by idiopathic, inherited pseudoxanthoma elasticum.",Penicillamine;Pseudoxanthoma elasticum;Trientene dihydrochloride;Wilson's disease;adult;article;case report;clinical trial;dermatofibroma;dysphagia/th [Therapy];dysphonia;dyspnea/dt [Drug Therapy];elastic fiber;esophagus biopsy;esophagus dilatation;esophagus myotomy;human;idiopathic disease;lung biopsy;male;microscopy;priority journal;pseudoxanthoma elasticum/si [Side Effect];skin biopsy;systemic disease;transmission electron microscopy;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy],"Coatesworth, A. P.;Darnton, S. J.;Green, R. M.;Cayton, R. M.;Antonakopoulos, G. N.",1998,,,0,0,
2485,Metallothionein and apoptosis in the toxic milk mutant mouse,"Toxic milk mutant (tx) mice accumulate excess copper (Cu) in liver with age and develop symptoms similar to those seen in human Wilson disease. Because metallothionein (MT) is the major Cu-binding protein in tx mouse liver and Cu-MT can enhance lipid peroxidation Initiated by an organic hydroperoxide, the potential genotoxicity of Cu-MT in tx mice was assessed in male tx mice (11 to 12 months old) and in age- and sex-matched control wild- type (DL) mice. Toxic milk mutant mice, but not control DL mice, developed regenerative liver nodules (tx-N) with normal histologic appearance. Residual, non-nodular tx mouse liver (tx-R) was microscopically abnormal with large, atypical hepatocytes. The levels of Cu, zinc (Zn), and MT, and the numbers of apoptotic cells (APC) in tx-N, tx-R, and DL livers were measured by atomic absorption spectrophotometry, <sup>109</sup>cadmium-heme assay, and the TUNEL method, respectively. Significantly higher levels of MT, Cu, and Zn, as well as increased numbers of APC were found in both tx-N and tx-R compared with DL mouse livers. Intense nuclear and cytoplasmic immunohistochemical staining for MT was observed in both normal and atypical hepatocytes of the tx mouse, whereas only cytoplasmic staining for MT was detected in DL mouse liver tissue. Accumulated Cu could be detected in tx-R and tx-N liver by rhodamine staining but was not detected in other tx mouse organs, or in mouse liver or other organs of DL. The number of APC and level of MT were significantly higher in tx-R liver compared with both tx-N and DL liver. These results suggest that: (a) aged tx mouse accumulate excess Cu in liver accompanied by striking morphologic changes, and (b) although MT binds to Cu in tx mouse liver, the presence of high Cu-MT and Cu in the nucleus can be genotoxic and may lead to enhanced apoptosis.",animal experiment;animal tissue;apoptosis;article;controlled study;copper metabolism;female;genotoxicity;lipid peroxidation;liver toxicity;male;mouse;nonhuman;priority journal;Wilson disease;metallothionein,"Deng, D. X.;Ono, S. I.;Koropatnick, J.;Cherian, M. G.",1998,February,,0,0,
2486,"Age-related copper, zinc, and iron metabolism in Long-Evans cinnamon rats and copper-eliminating effects of D-penicillamine and trienthine-2HCl","The Long-Evans cinnamon (LEC) rat is an animal model of human Wilson's disease. The hepatic copper content of LEC rats increased in an age-dependent manner from 4-5 days of age and was maintained at a high level from 15-16 weeks of age. The renal copper content of LEC rats showed a tendency to increase from 10 weeks of age and increased rapidly from 15 weeks of age. No difference in whole-brain copper concentration was observed between LEC and Long-Evans agouti (LEA) rats. LEC rats treated with D-penicillamine and trienthine-2HCl had reduced liver dysfunction. These agents reduced the hepatic copper content by ~ 1/2-2/3 and the renal copper content to within the normal range. They also decreased the copper content of hair and nails, and there was also a good correlation between the copper content of liver and white hair.",Hepatitis;P-type ATPase;Wilson disease;aging;animal experiment;animal model;animal tissue;article;brain level;controlled study;copper metabolism;female;hair;iron metabolism;kidney;liver dysfunction;liver level;liver metabolism;male;nail;nonhuman;priority journal;rat;Wilson disease/cn [Congenital Disorder];zinc metabolism;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dv [Drug Development];penicillamine/pd [Pharmacology];trientine;zinc/ec [Endogenous Compound],"Shimizu, N.;Fujii, Y.;Saito, Y.;Yamaguchi, Y.;Aoki, T.",1997,,http://dx.doi.org/10.1002/%28SICI%291520-670X%281997%2910:2%3C49::AID-JTRA2%3E3.0.CO;2-#,0,0,
2487,Oxidative stress in LEC rats evaluated by plasma antioxidants and free fatty acids,"The Long-Evans cinnamon (LEC) rat, an animal model of Wilson's disease, develops hepatitis and liver cancer. Since LEC rats accumulate copper especially in the liver and since copper is a good catalyst of oxidation, selected plasma markers of oxidative stress in LEC rats and control Long-Evans agouti (LEA) rats were measured. Significant decrease in the plasma ascorbate level was observed even at the onset of hepatitis, suggesting that LEC rats are under oxidative stress because ascorbate is very susceptible to oxidation. The ratio of plasma ubiquinol-9, another oxidatively vulnerable antioxidant, to ubiquinone-9 in LEC rats also decreased significantly after the onset of hepatitis. Oxidative damage in the liver of LEC rats after the onset of hepatitis was also suggested by a decrease in the ratio of polyunsaturated fatty acids (PUFA) to free fatty acids (FFA) and an increase in the palmitoleic acid to FFA ratio in plasmas of LEC rats when compared with LEA rats since PUFA are vulnerable to oxidation and DELTA<sup>9</sup> desaturase is activated in order to compensate for the loss of PUFA. All of the above changes and hepatitis were prevented by adding a copper chelating agent, trientine dihydrochloride, to the drinking water of LEC rats. These data suggest that oxygen radicals may play an important role in the development of hepatitis and the subsequent liver cancer.",Ascorbate;Copper;Hepatitis;Palmitoleic acid;Polyunsaturated fatty acids;Ubiquinol;animal experiment;animal model;animal tissue;article;blood level;controlled study;fatty acid blood level;fatty acid metabolism;liver injury;liver metabolism;male;nonhuman;oral drug administration;oxidative stress;priority journal;rat;Wilson disease/cn [Congenital Disorder];acyl coenzyme A desaturase/ec [Endogenous Compound];antioxidant/ec [Endogenous Compound];ascorbic acid/ec [Endogenous Compound];chelating agent;copper/ec [Endogenous Compound];fatty acid/ec [Endogenous Compound];palmitoleic acid/ec [Endogenous Compound];polyunsaturated fatty acid/ec [Endogenous Compound];trientine/dv [Drug Development];ubiquinone/ec [Endogenous Compound],"Yamamoto, Y.;Sone, H.;Yamashita, S.;Nagata, Y.;Niikawa, H.;Hara, K.;Nagao, M.",1997,,http://dx.doi.org/10.1002/%28SICI%291520-670X%281997%2910:2%3C129::AID-JTRA10%3E3.0.CO;2-T,0,0,
2488,The complex therapy of Wilson's disease. [Dutch],,copper metabolism;heredity;human;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pipradol;tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;zinc/dt [Drug Therapy],"Kwint, H. F.;Bouvy, M.",1997,,,0,0,
2489,"Influence of 3,4-Dihydroxybenzoic acid on metal ion concentrations in guinea pig tissues after copper intoxication","3,4-Dihydroxybenzoic acid (3,4-dhbH<inf>3</inf> or protocatechuic acid) is a copper chelator which has potential as an agent for the treatment of copper- overload disease (Wilson's disease). The present investigation describes the fluctuation in copper, magnesium, zinc and calcium (Cu, Mg, Zn, Ca) concentrations in tissues of guinea pigs intoxicated with Cu after the administration of 3,q-dhbH<inf>3</inf>. We investigated the efficacy of 3,q-dhbH<inf>3</inf> to eliminate Cu from poisoned guinea pigs, as well as to assess the changes in concentrations of Zn, Ca and Mg which normally occur in the tissues of experimental animals. The results are in agreement with other experimental data when we administered drugs capable of forming complexes with metal ions. Although 3,4-dhbH<inf>3</inf> is capable of forming in vitro complexes with Cu, it can not be used successfully for chelation therapy of Cu intoxication, but its effectiveness as a ligand for Ca, Zn and Mg mobilization is discussed.",animal experiment;animal model;article;chelation;drug effect;guinea pig;heavy metal poisoning/dt [Drug Therapy];metal binding;nonhuman;copper;protocatechuic acid/dt [Drug Therapy],"Kotsaki-Kovatsi, V. P.;Vafiadou, A. J.;Koehler-Samuilidou, G.;Kovatsis, A.",1997,,,0,0,
2490,Wilson's disease. Different forms of onset. [Spanish],"Wilson's disease is characterized by a disorder of copper metabolism and the mechanism responsible for the basic defect still unknown. It's transmitted by autosomal recesisve inheritance in relation to chromosome 13. The presenting signs depend on the age of the patient. In children aged 4 to 10 years, it ranges from asyntomatic forms with minimal laboratory evidence to acute liver failure and death. The course of Wilson's disease is variable, but it normally becomes chronic, occasionally associatted with neurological, renal, haematological and ocular abnormalities. The diagnosis is based on serun and urinary cooper levels, serum cerulopasmin concentration and the histological study of the tissues in which the metal is deposited (liver, kidneys, CNS, etc.). Copper chelating agents (penicillamine, trientene, zinc sulphate) can be administered as a bridge to liver transplantation, which is the definitive treatment for this metabolic disorder. We present a retrospective study of 7 cases of Wilson's disease diagnosed in our center, focusing on the presenting signs, biochemical abnormalities, diagnostic methods, clinical course and treatment.",Children;Liver transplantation;Wilson's disease;adolescent;article;child;clinical article;copper blood level;copper metabolism;human;onset age;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Sanchez, C. S.;Campdera, J. A. G.;Perez, J. L. M.;Robert, L. B. H.;Sanchez, M. I. G.;Gonzalez, A. S.",1997,,,0,1,
2491,Ultrastructural changes in the intestine of rats fed high-zinc diets,"The feeding of high-zinc diets to humans is often used as therapy for patients with Wilson's disease, an autosomal recessive disorder of copper accumulation. There seem to be no outward adverse effects of this treatment; however, preliminary studies in our laboratory have shown apparent weaknesses in the intestinal wall of rats fed high-zinc diets. As a consequence, this study was carried out to determine if feeding high-zinc diets to rats would affect the ultrastructural morphology of the small intestine. The effects of treatment on copper status of the rats also were determined. Weanling male rats were fed diets containing either 35 or 350 mg of zinc/kg. After 7 weeks, blood and various tissues were collected to measure copper status indicators, and portions of the upper duodenum were excised and prepared for light and electron microscopy. Results showed that rats fed high-zinc diets had significantly lower copper status as indicated by low serum copper, serum ceruloplasmin activity, and liver copper, than rats fed normal-zinc diets. Liver superoxide dismutase or cytochrome c oxidase activities were not affected by high zinc. Observations of sections of the duodenum by electron microscopy showed that non-assembled collagen molecules of the lamina propria were more often disorganized and formed tangled masses in rats fed the high-zinc diet than in those fed normal-zinc diets. This suggests that low copper status caused by high-zinc feeding might be affecting the activity of lysyl oxidase, a copper-dependent enzyme, and thus crosslinking of the collagen molecules. However, these observations did not always correlate with low copper status. Other possible explanations include a direct competition between zinc and copper for sites on lysyl oxidase, zinc blocking of aldehyde residues on the collagen molecule, or some unrecognized process involving other enzymes or other aspects of collagen assembly. Whether such processes or affinities actually exist is still under investigation.",Collagen;Copper;Electron microscopy;Intestine;Rats;Ultrastructure;Zinc;animal experiment;animal tissue;article;cell ultrastructure;ceruloplasmin blood level;copper blood level;diet;duodenum;intestine wall;lamina propria;male;microscopy;nonhuman;priority journal;rat;small intestine;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];protein lysine 6 oxidase/ec [Endogenous Compound],"Reeves, P. G.;Newman Jr, S. M.",1997,,http://dx.doi.org/10.1002/%28SICI%291520-670X%281997%2910:1%3C37::AID-JTRA5%3E3.0.CO;2-1,0,0,
2492,A case of Wilson's disease in which brain magnetic resonance imaging finding improved after D-penicillamine therapy,"We report a case of Wilson's disease which showed improvement of brain magnetic resonance imaging findings after D-penicillamine treatment. The patient was a 16-year-old boy who was admitted because of liver dysfunction. The diagnosis of Wilson's disease was established with abnormal biochemical findings, including low plasma concentrations of copper and ceruloplasmin. Neurologic examination showed sluggish behavior and a decreased intelligence quotient. On magnetic resonance imaging, low-intensity areas on T1-weighted images and high-intensity areas on T2-weighted images were seen in the bilateral basal nuclear region and in the caudate nucleus, putamen, globus pallidus, and the tegmentum of the midbrain and pons. After 70 weeks of treatment with D-penicillamine, magnetic resonances imaging findings normalized and clinical symptoms improved. We suggest that this improvement in brain magnetic resonance imaging findings indicates that deposition of copper in the brain tissue decreased with treatment.",D- penicillamine;Magnetic resonance imaging (MRI) findings;Wilson's disease;adolescent;article;brain region;case report;ceruloplasmin blood level;copper blood level;drug efficacy;follow up;human;liver dysfunction/dt [Drug Therapy];male;nuclear magnetic resonance imaging;treatment outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Naito, Y.;Suzuki, M.;Furutani, N.;Nakabayashi, H.;Fujise, K.;Harada, J.;Watanabe, R.",1997,,,0,0,
2493,Arthropathy of Wilson's disease presenting as noninflammatory polyarthritis [5],,adult;arthralgia;case report;clinical feature;disease association;female;human;letter;liver biopsy;osteoarthritis/di [Diagnosis];osteoarthritis/si [Side Effect];polyarteritis;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Narvaez, J.;Alegre-Sancho, J. J.;Juanola, X.;Roig-Escofet, D.",1997,,,0,0,
2494,Pediatric Wilson's disease: Presentation and management,"Eleven patients (4 males, 7 females) with Wilson's disease who presented before 18 years of age are described. The mean age onset of symptoms was 11.2 +/- 3.9 (SD) years. The mean age at diagnosis was 13.3 +/- 3.4 (SD) years. All patients had hepatic manifestations of the disease when diagnosed: cirrhosis (6 patients), chronic hepatitis (2) and fulminant hepatic failure (3). Three patients were asymptomatic at diagnosis. Two of the symptomatic patients presented with new undescribed manifestations: one with blurred vision and the other with acalculous cholecystitis. At diagnosis, 6 patients had Kayser Fleischer rings and 5 had hemolytic anemia. The three patients with fulminant hepatic failure had hemolysis with relatively low serum aminotransferase and alkaline phosphatase levels, possibly helpful findings for rapid diagnosis of Wilson's disease in such presentation. Ten patients were treated with penicillamine. Liver transplantation was performed in 4 patients, 2 of which presented with fulminant hepatic failure. One patient died while waiting for liver transplantation, the remainder of the patients live free of symptoms. It is important to be aware of the different manifestations of Wilson's disease in the pediatric population, in order to make appropriate evaluations in a timely manner to facilitate early diagnosis and appropriate treatment.",acalculous cholecysitis;blurred vision;liver transplantation;Wilson's disease;acalculous cholecystitis/di [Diagnosis];acalculous cholecystitis/et [Etiology];adolescent;alkaline phosphatase blood level;aminotransferase blood level;article;ceruloplasmin blood level;child;chronic hepatitis/di [Diagnosis];chronic hepatitis/et [Etiology];clinical article;copper metabolism;dermatitis/si [Side Effect];female;human;liver cirrhosis/di [Diagnosis];liver cirrhosis/et [Etiology];liver failure/di [Diagnosis];liver failure/et [Etiology];male;onset age;urinary excretion;visual impairment/di [Diagnosis];visual impairment/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper ion/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Ament, M. E.",1997,,,0,0,
2495,Elastosis perforans serpiginosa and Wilson's disease,,adult;carbon dioxide laser;case report;clinical feature;conference paper;cutis laxa/si [Side Effect];disease association;disease classification;drug hypersensitivity/si [Side Effect];drug mechanism;drug response;human;male;morphea/si [Side Effect];pemphigus vulgaris/si [Side Effect];pseudoxanthoma elasticum/si [Side Effect];rash/si [Side Effect];skin disease/si [Side Effect];skin disease/th [Therapy];Wilson disease/dt [Drug Therapy];isotretinoin/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Di Lella, G.;Colonna, L.;Cianchini, G.;Pallotta, S.;Puddu, P.",1997,,,0,0,
2496,Successful pregnancy in a neurologically impaired woman with Wilson's disease,Patients with treated Wilson's disease and no residual impairments should have successful pregnancies. We report a case of a neurologically impaired patient with Wilson's disease who had a successful pregnancy with no complications. This is the first case to document that compliance with penicillamine therapy as low as 500 mg/day avoids placental and fetal copper accumulation.,Copper;liver diseases;pregnancy;Wilson's disease;adult;article;brain disease/co [Complication];case report;copper metabolism;female;human;pregnancy complication;priority journal;treatment outcome;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Berghella, V.;Steele, D.;Spector, T.;Cambi, F.;Johnson, A.",1997,,http://dx.doi.org/10.1016/S0002-9378%2897%2970577-5,0,0,
2497,Wilson's disease. [Italian],"Wilson's disease is a rare inherited metabolic disorder usually characterized by liver and/or neurological degeneration. Unlike most genetically transmitted diseases, it rapidly responds to pharmacological treatment in case of early diagnosis and treatment. Often, however, as this disease presents with aspecific symptoms, patients are wrongly diagnosed as psychiatric cases or as having generic chronic liver disease and the true cause of symptoms is only discovered at a much later stage. The authors give a detailed review of the literature with the aim of presenting the most recent research on the main aspects of this disease and offering a practical and simple approach to early diagnosis.",chronic liver disease;hepatolenticular degeneration;hereditary disease;metabolic disorder;clinical feature;heredity;human;pathogenesis;prognosis;review;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Bonfissuto, G.;Magliarisi, C.;Soresi, M.;Bascone, F.;Costanza, G.;Carroccio, A.;Montalto, G.",1997,January,,0,0,
2498,Decreased carbonic anhydrase III levels in the liver of the mouse mutant 'toxic milk' (tx) due to copper accumulation,"The mouse mutant 'toxic milk' (tx) is characterized by marked hepatic accumulation of copper, similar to that found in patients with the genetic disorder of copper transport, Wilson disease. In addition, lactating tx females produce copper-deficient milk. To characterize further the biochemical basis of this defect, Western blots of tissue extracts from normal and tx mice were probed with various heavy-metal radioisotopes (<sup>63</sup>Ni, <sup>65</sup>Zn and <sup>64</sup>Cu). A 30 kDa Ni/Zn-binding polypeptide was found to be markedly decreased in the livers of the tx mice. This protein was isolated from normal adult mice using a procedure based on Ni-chelation chromatography. The amino acid sequences of two CNBr peptides were identical with portions of the mouse skeletal muscle carbonic anhydrase III (CAIII) sequence. Two other peptides sequenced had closely related sequences to that of CAIII, but with two differences in 45 amino acids. These two peptides may be derived from a novel CAIII isoform, which we term CAIIIB to distinguish it from the published form, CAIIIA. We isolated a cDNA clone corresponding to CAIIIA and used this to show that CAIIIA mRNA was also decreased in the mutant liver, but not in muscle. Copper loading of normal mice also decreased hepatic CAIIIA mRNA, suggesting that the decrease in CAIII mRNA in the tx mouse liver is a secondary consequence of the high copper levels in the liver.",amino acid sequence;animal experiment;animal model;animal tissue;article;biochemistry;enzyme activity;genetic disorder;immunoblotting;liver;liver metabolism;mouse;mouse mutant;nonhuman;priority journal;Wilson disease;carbonate dehydratase/ec [Endogenous Compound];copper ion/ec [Endogenous Compound],"Grimes, A.;Paynter, J.;Walker, I. D.;Bhave, M.;Mercer, J. F. B.",1997,,,0,0,
2499,Copper transport and its alterations in Menkes and Wilson diseases,,chelation therapy;copper metabolism;drug bile level;gastrointestinal absorption;gastrointestinal transit;human;intracellular transport;ion transport;membrane transport;Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];nonhuman;priority journal;protein binding;review;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];albumin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper complex/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];histidine copper/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;zinc/dt [Drug Therapy],"DiDonato, M.;Sarkar, B.",1997,27 Feb,http://dx.doi.org/10.1016/S0925-4439%2896%2900064-6,0,0,
2500,"MR imaging of wilson's disease: Contrast enhancement of the cerebral cortex, and corticomedullary junction","A patient with Wilson's disease is reported whose brain MR imaging study disclosed enhancement of the cerebral cortex, and corticomedullary junction after administration of contrast medium, in the absence of a clinically detectable ischemic condition. It is difficult to explain such contrast enhancement. However, we would suggest that a 'vasculitis' secondary to accumulation of copper in the walls of the small vessels may be the causative factor. Further studies are required to investigate the clinical and radiological significance of contrast enhancement of the cerebral cortex and corticomedullary junction on MR images in patients with Wilson's disease.",Brain;Diseases;MR studies;Wilson's disease;article;brain cortex;brain disease/di [Diagnosis];case report;child;contrast enhancement;diagnostic imaging;human;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/dt [Drug Therapy];male;medulla oblongata;neuroradiology;nuclear magnetic resonance imaging;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];contrast medium;gadolinium pentetate;penicillamine/dt [Drug Therapy],"Sener, R. N.",1997,May/June,http://dx.doi.org/10.1016/S0895-6111%2897%2900012-8,0,0,
2501,The contraceptive choice for a Wilson's disease patient with chronic liver disease,"Preserved fertility stains is frequently encountered in patients with Wilson's disease, and contraceptive counseling may, therefore, be a relevant tissue. Yet, several contraceptive methods can adversely influence the hepatic function, and the efficacy of others may be affected by the liver disease. We describe a patient with Wilson's disease manifested by cirrhosis, portal hypertension, and bleeding esophageal varices who underwent termination of pregnancy at 9 weeks' gestation. Following the procedure, contraceptive advice was sough in order to postpone conception until portal hypertension was controlled and hepatic function improved. Intramuscular depto medroxyprogesterone acetate was administered and tolerated well by the patient. A detailed discussion of the contraceptive options for patients with chronic liver disease, in general, and Wilson's disease, in particular, follows the case report.",Contraception;Liver disease;Portal hypertension;Pregnancy;Wilson's disease;adult;article;case report;chronic liver disease/co [Complication];drug tolerability;esophagus varices bleeding/co [Complication];female;human;human tissue;intramuscular drug administration;intrauterine contraceptive device;patient counseling;portal hypertension/co [Complication];pregnancy termination;treatment contraindication;Wilson disease;medroxyprogesterone acetate/pd [Pharmacology];nonoxinol 9/pd [Pharmacology];penicillamine/pd [Pharmacology],"Haimov-Kochman, R.;Ackerman, Z.;Anteby, E. Y.",1997,October,http://dx.doi.org/10.1016/S0010-7824%2897%2900141-8,0,0,
2502,Pathology of mineral metabolism. [Spanish],"Among the minerals whose presence is quantitatively important for the organism (macro minerals), certain ones-sodium, chlorine, potassium-are metabolically linked to water, the most abundant element in the human body. Related metabolic disturbances are mostly due to water imbalance and they are therefore studied within the context of water metabolism disorders. Other elements-calcium, phosphorous and magnesium-contribute to bone metabolism under the influence of the calcitrophic hormones : parathormone, calcitonine and 1.25 dihidroxicolecalciferol. Beyond the neonatal stage, the distinctive diagnosis of hipocalcaemia is based upon the level of phosphates, parathormone and vitamin D derivatives to identify the different types of rickets or parathyroid disfunction. Likewise, the causal identification of hipercalcaemia hinges on parathyroid function. The microminerals, so-called because of their trace occurrence in the organism, play an irreplaceable role in various enzyme functions. Some are (iron, iodine) closely linked to specific organic functions (synthesis of haemoglobin and mioglobin and tiroxine, respectively). Others can suffer nutritional abnormalities but perhaps the most serious pathologies derive from genetic predisposition, such as Wilson's and Menkes' diseases for copper or Enteropatic Acrodermatitis for zinc.",Hipercalcaemia;Hipocalcaemia;Mineral metabolism;Trace elements;acrodermatitis enteropathica;article;bone metabolism;fluid balance;genetic predisposition;hormonal regulation;human;Menkes syndrome;metabolic disorder/et [Etiology];metabolic regulation;pathogenesis;pathophysiology;Wilson disease;calcium ion/ec [Endogenous Compound];chlorine/ec [Endogenous Compound];copper/ec [Endogenous Compound];iodine/ec [Endogenous Compound];iron/ec [Endogenous Compound];parathyroid hormone/ec [Endogenous Compound];phosphate/ec [Endogenous Compound];potassium/ec [Endogenous Compound];sodium/ec [Endogenous Compound];vitamin D derivative/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Crespo, M. F. R.",1997,,,0,0,
2503,Wilson's disease,"We describe a patient who had severe neurologic symptoms, psychiatric abnormalities, and secondary amenorrhea superimposed on a history of hemolytic anemia and micronodular cirrhosis attributed to hemochromatosis. The correct diagnosis of Wilson's disease was delayed until the appearance of Kayser-Fleischer rings and a low serum ceruloplasmin level. Appropriate treatment ameliorated symptoms, and maintenance therapy has been effective in retarding progression. It is essential to consider Wilson's disease in patients with unexplained hepatic, neurologic, and psychiatric dysfunction, because appropriate early medical treatment can prevent further organ damage and reduce the risk of permanent damage to the liver and brain.",adult;article;case report;ceruloplasmin blood level;computer assisted tomography;female;hemochromatosis/di [Diagnosis];hemochromatosis/th [Therapy];human;liver cirrhosis/di [Diagnosis];nuclear magnetic resonance imaging;phlebotomy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hemosiderin/ec [Endogenous Compound];penicillamine;tetrathiomolybdate ammonium/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Baban, N. K.;Hubbs, D. T.;Roy, T. M.",1997,May,,0,0,
2504,Contribution to the abdominal form of issue of Wilson's disease. [German],,FRIEDREICH'S ataxia;Liver cirrhosis;Oesophageal varicosis;Psychosocial maldevelopment;Splenomegaly;WILSON'S disease;alcohol liver cirrhosis;aminotransferase blood level;article;behavior disorder;case report;child;differential diagnosis;esophagus varices;female;Friedreich ataxia;hepatitis;human;liver disease;splenomegaly/su [Surgery];urinary excretion;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];aminotransferase/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Fehlow, P.",1997,,,0,0,
2505,Computer tomography and magnetic resonance imaging in Wilson's disease. [French],,brain;ct;mr;Wilson's disease;adult;article;brain atrophy/cn [Congenital Disorder];brain atrophy/di [Diagnosis];brain atrophy/dt [Drug Therapy];case report;computer assisted tomography;human;male;nuclear magnetic resonance imaging;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Dietemann, J. L.;Goursaud, O.;Tong, G.;Dragomir, R.;Zollner, G.;Tranchant, C. H.",1997,,,0,0,
2506,Elevated liver enzymes in pregnant woman with Wilson's disease: A case report. [Japanese],,D-penicillamine;Liver enzyme;Pregnancy;Wilson's disease;adult;article;case report;enzyme blood level;female;human;liver function test;nuclear magnetic resonance imaging;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Kohno, Y.;Toda, T.;Terakawa, N.",1997,November,,0,0,
2507,Wilson's disease in children: Description of a patient treated with oral zinc sulfate. [Spanish],A 13-year-old asymptomatic male with persistently high transaminase levels was diagnosed as hepatic Wilson's disease. He was treated with oral zinc sulfate (150 mg/day). After 6 months his liver function was normal and there were no side effects.,transaminase elevation;Wilson's disease;zinc sulfate;adolescent;article;case report;human;liver function;male;oral drug administration;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Martinez Badas, I.;Crespo Chozas, D.;Olivares, F.;Hernandez, F.;Parejo Carranza, R.;Camarero Salces, C.",1997,,,0,0,
2508,Extending the limit on the size of adult recipient in living donor liver transplantation using extended right lobe graft,"The feasibility of adult-to-adult living donor liver transplantation (LDLT) is restricted by the adequacy of the graft size. A left lobe graft from a relatively small donor will not meet the metabolic demand of a larger recipient. We report a successful LDLT performed on a 90-kg man using an extended right lobe graft weighing 910 g from his relatively smaller-size brother. The donor-to-recipient body weight ratio was only 0.82. No homologous blood transfusion was required for the donor, and the donor recovered uneventfully except for mild transient hyperbilirubinemia. The graft provided adequate function for the metabolic needs of the recipient despite postoperative septic complications. Both donor and recipient were well with normal liver function at 4 months after operation. LDLT using the extended right lobe liver graft can extend the limit on the size of the adult recipient and may be a viable option even when the donor is relatively small compared with the recipient.",adult;angiography;article;case report;computer assisted tomography;echography;human;kidney disease/co [Complication];liver biopsy;liver failure/su [Surgery];liver function;liver lobectomy;liver size;liver transplantation;living donor;male;priority journal;recipient;sepsis/co [Complication];sepsis/dt [Drug Therapy];sepsis/su [Surgery];surgical technique;volumetry;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];antibiotic agent/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];azathioprine/cb [Drug Combination];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cyclosporin/cb [Drug Combination];hemoglobin/ec [Endogenous Compound];okt 3;penicillamine/dt [Drug Therapy];steroid/cb [Drug Combination],"Lo, C. M.;Fan, S. T.;Liu, C. L.;Lo, R. J. W.;Lau, G. K. K.;Wei, W. I.;Li, J. H. C.;Ng, I. O. L.;Wong, J.",1997,27 May,http://dx.doi.org/10.1097/00007890-199705270-00027,0,0,
2509,A child with icterus and a fat belly. [Dutch],,article;ascites/dt [Drug Therapy];ascites/th [Therapy];case report;diet;human;jaundice/et [Etiology];liver biopsy;liver dysfunction;liver transplantation;male;school child;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];albumin/dt [Drug Therapy];ammonia/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"De Bree, R.;Hogeman, P. H. G.;Duran, M.;Houwen, R. H. J.;Wielders, J. P. M.",1997,,,0,0,
2510,The mechanism of excretion of trientine from the rat kidney: Trientine is not recognized by the H<sup>+</sup>/organic cation transporter,"Trientine dihydrochloride is used to treat Wilson's disease by chelating copper and increasing its urinary excretion. The mechanism of renal excretion of trientine has been investigated in-vivo and in-vitro. Trientine clearance in the rat was significantly faster than creatinine clearance. When trientine and the same number of moles of copper ions were administered simultaneously to the rat, however, trientine clearance decreased to almost the same level as the creatinine clearance. To clarify this active excretion system for trientine, the uptake of trientine and a physiological polyamine compound, spermine, was investigated using rat renal brush-border membrane vesicles. Although, because trientine and spermine are organic cations, the H<sup>+</sup>/organic cation transporter is expected to recognize these compounds, neither an outwardly directed H<sup>+</sup> gradient nor an inward Na<sup>+</sup> gradient stimulated trientine uptake. [<sup>14</sup>C]Spermine uptake was, nevertheless, trans-stimulated by both unlabelled spermine and trientine and the trans-stimulating effect of spermine on trientine uptake was, furthermore, completely abolished by addition of copper ions to the incubation medium. These results suggest that there is a specific transport system for spermine and trientine on the renal brush-border membrane. This transport system contributes to the secretion of trientine in the kidney proximal tubule but does not recognize the trientine-copper complex.",animal experiment;animal tissue;article;controlled study;creatinine clearance;drug excretion;drug uptake;intravenous drug administration;kidney proximal tubule;kidney tubule epithelium;male;membrane vesicle;nonhuman;proton transport;rat;sodium transport;urinary excretion;copper ion;creatinine/ec [Endogenous Compound];proton/ec [Endogenous Compound];sodium ion/ec [Endogenous Compound];spermine;trientine/pk [Pharmacokinetics],"Kobayashi, M.;Tanabe, R.;Sugawara, M.;Iseki, K.;Miyazaki, K.",1997,April,,0,0,
2511,Menkes disease: Recent advances and new aspects,"Copper is the third most abundant trace element in the body, after iron and zinc, and it is required for the normal function of several important copper enzymes. However, the same element in excess is highly toxic and has detrimental effects. Fine regulation of intracellular copper homeostasis is therefore vitally important and disturbance of this balance is reflected in two hereditary disorders, Menkes disease and Wilson disease. In recent years, remarkable progress has been made in this field following the isolation of the defective gene in Menkes disease (MD), which will be the main focus of this review. Progressive neurodegeneration and connective tissue disturbances are the main manifestations of X linked recessive Menkes disease and most of the clinical features can be explained by malfunction of one or more copper enzymes. The disease locus has been mapped to Xq13.3 and the gene (MNK) defective in Menkes disease had been isolated by positional cloning. The protein product is predicted to be a copper binding P type ATPase (ATP7A), the first intracellular copper transporter described in eukaryotes. Identification of MNK led to a series of advances in a very short time. The mouse homologue of MNK had been isolated and the allelic relationship between MD and the occipital horn syndrome confirmed. Most importantly, the gene defective in Wilson disease was isolate using sequences specific to MNK and predicted protein product showed high homology to ATP7A. In this review we will outline these recent advances and their consequences with special reference to Menkes disease. Wilson disease will be described briefly, and the defective copper metabolism in both diseases will be summarised in the light of the mew insights. Finally, copper translocating ATPases identified in other species and their significance in understanding copper metabolism will be discussed.","Copper metabolism;Menkes disease;Wilson disease;amino acid sequence;amniocentesis;ceruloplasmin blood level;chorion villus sampling;chromosome 13q;chromosome Xq;clinical feature;connective tissue disease;copper blood level;differential diagnosis;DNA determination;gene isolation;gene locus;gene mutation;heterozygote detection;homeostasis;human;karyotype 46,XX;liver disease;Menkes syndrome/cn [Congenital Disorder];Menkes syndrome/di [Diagnosis];Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];nerve degeneration;nonhuman;prenatal diagnosis;priority journal;review;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];adenosine triphosphatase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper complex/dt [Drug Therapy];DNA/ec [Endogenous Compound];histidine copper/dt [Drug Therapy];messenger RNA/ec [Endogenous Compound];unclassified drug","Tumer, Z.;Horn, N.",1997,,,0,0,
2512,Atypical MRI features of Wilson's disease: High signal in globus pallidus on T1-weighted images,"Most reports of MRI in Wilson's disease have been of abnormal low-signal lesions on T1-weighted images and high signal intensity on T2-weighted images. In contrast, we report three patients who had high-signal lesions in the globus pallidus on T1-weighted images, a finding seen in patients with portal-systemic encephalopathy. The possible causes include the paramagnetic effect of copper or iron and accumulation of Alzheimer type II glial cells.",Magnetic resonance imaging;Portal-systemic encephalopathy;Wilson's disease;adolescent;adult;article;brain disease/co [Complication];brain disease/di [Diagnosis];brain injury/co [Complication];brain injury/di [Diagnosis];case report;female;glia cell;globus pallidus;human;liver transplantation;male;mesencephalon;neurologic examination;nuclear magnetic resonance imaging;priority journal;putamen;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Mochizuki, H.;Kamakura, K.;Masaki, T.;Okano, M.;Nagata, N.;Inui, A.;Fujisawa, T.;Kaji, T.",1997,,http://dx.doi.org/10.1007/s002340050386,0,0,
2513,(D)-Penicillamine increases hepatic oxalate production resulting in hyperoxaluria,"Purpose: To determine whether (D)-penicillamine is effective in reducing hepatic oxalate production and urinary oxalate excretion. Materials and Methods: (D)-Penicillamine was administered orally to rats to determine its effect on urinary oxalate excretion and used in isolated rat hepatocytes to investigate the effect of (D)-penicillamine on oxalate production from glycolate. Studies involving hepatic aminotransferases and hepatocytes isolated from (D)-penicillamine treated rats were used to clarify the discrepancy between the in vitro and in vivo results. Results: In hepatocytes (D)-penicillamine lead to a significant reduction in oxalate production from glycolate. In vivo however, (D)-penicillamine led to a significant increase in urinary oxalate excretion and a decrease in plasma aminotransferase activity. Hepatic aminotransferases are involved in diverting oxalate precursors from oxalate production. In vitro, (D)-penicillamine was shown to inhibit hepatic aminotransferases. Hepatocytes isolated from (D)- penicillamine-treated rats produced significantly more oxalate than controls. Conclusions: These results indicate that (D)-penicillamine increases hepatic oxalate production and urinary oxalate excretion. (D)-penicillamine therefore has no therapeutic potential for reducing endogenous oxalate production and urinary oxalate excretion. Moreover, in conditions such as Wilson's Disease which is often associated with hypercalcuria, its use may be contraindicated.",beta- aminothiol:glyoxalate adduct;aminotransferase;hyperoxaluria;penicillamine;urolithiasis;aminotransferase blood level;animal cell;animal experiment;animal model;animal tissue;article;controlled study;enzyme activity;hyperoxaluria/et [Etiology];liver cell;male;nonhuman;priority journal;rat;stereochemistry;Wilson disease;aminothiol;aminotransferase/ec [Endogenous Compound];calcium oxalate;glycolic acid/ec [Endogenous Compound];oxalic acid;penicillamine/an [Drug Analysis];penicillamine/dv [Drug Development];penicillamine/pd [Pharmacology],"Baker, P. W.;Bais, R.;Rofe, A. M.",1997,March,http://dx.doi.org/10.1016/S0022-5347%2801%2965155-3,0,0,
2514,Neurology and the liver,,article;hepatic encephalopathy/di [Diagnosis];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/et [Etiology];liver;liver failure/di [Diagnosis];liver failure/th [Therapy];neurology;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];benzodiazepine derivative/dt [Drug Therapy];flumazenil/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Jones, E. A.;Weissenborn, K.",1997,,,0,0,
2515,Fulminant hepatic failure as the first manifestation of Wilson disease: A report of two cases,"Two cases of fulminant hepatic failure as a first manifestation of Wilson disease are reported. They were diagnosed as acute hemolytic anemia initially, and took a fatal course despite intensive medical therapy. The main object of this report is to emphasize that Wilson disease must be included in the differential diagnosis of fulminant hepatic failure in children. Liver transplantation is the only effective means of treatment in patients presenting with fulminant hepatic failure, but this procedure is difficult to perform because of insufficient organ donation in Taiwan. The best treatment for Wilson disease is prevention through diagnosis at a presymptomatic stage, and institution of life-long therapy with D- penicillamine.",Fulminant hepatic failure;Wilson disease;article;case report;clinical feature;diagnostic accuracy;diagnostic error;diagnostic value;early diagnosis;hemolytic anemia;human;liver failure;liver transplantation;treatment planning;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/pc [Prevention];penicillamine/dt [Drug Therapy],"Chung, C. C.",1997,,,0,0,
2516,A case of living related liver transplantation for Wilsonian fulminant hepatitis. [Japanese],"We reported a 13-year-old girl with Wilsonian fulminant hepatitis. The diagnosis was suspected clinically and was later confirmed by chemical and pathologic studies. She was admitted to our hospital with acute hepatic failure and severe hemolysis. Plasmapheresis as will as oral D-penicillamine intake did not show any improvement. On the 94th day, the patient received successful living related liver transplantation (LRLT). Donor was her mother. The patients who present severe intravascular hemolysis as a initial manifestation of Wilson's disease have very poor prognosis, because almost all these patients are in the state of decompensated liver cirrhosis and chelating agents such as D-penicillamine are not effective. In foreign countries, liver transplantation is indicated for such cases and has been able to rescue many patients. In conclusion, LRLT is a effective therapy for Wilsonian fuluminant hepatitis in Japan.",adolescent;article;case report;chelation;female;hemolysis/co [Complication];hepatitis/di [Diagnosis];hepatitis/su [Surgery];human;Japan;liver cirrhosis/co [Complication];liver failure/co [Complication];liver function;liver transplantation;treatment outcome;Wilson disease,"Komatsu, H.;Inui, A.;Fujisawa, T.;Ohkawa, T.;Miyagawa, Y.;Uemoto, S.;Inomata, Y.;Tanaka, K.",1996,,,0,0,
2517,Wilson's disease presenting as haemolytic anaemia and its successful treatment with penicillamine and zinc,"Haemolysis is an uncommon first manifestation of Wilson's disease. We describe a young woman who presented with episodic haemolysis and abnormal liver functions; the diagnosis of Wilson's disease was not made until nine months later. She responded well to a combination of penicillamine and zinc. This report underscores the importance of considering Wilson's disease as a cause in a patient with haemolysis of uncertain aetiology, since the disease can be successfully treated in the early stages. The mechanism of oxidative damage to erythrocytes by the excessive copper and the present role of zinc therapy are also discussed.",cirrhosis;coagulopathy;oxidative damage;penicillamine;zinc;adult;article;case report;cell damage;female;hemolysis;hemolytic anemia/co [Complication];hemolytic anemia/et [Etiology];human;oral drug administration;oxidative stress;pathogenesis;symptomatology;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Kong, H. L.;Yap, I. L. E.;Kueh, Y. K.",1996,December,,0,0,
2518,Wilson disease and idiopathic copper toxicosis,"The pathogenic agent of both Wilson disease (WD) and non-Indian childhood cirrhosis (which we term idiopathic copper toxicosis, or ICT) is copper accumulating to excess in the liver. Inheritance of a pair of alleles of an autosomal recessive gene on chromosome 13 is necessary and sufficient to cause such copper accumulation in WD; reducing the dietary intake of copper cannot prevent the development of WD. In contrast, the lethal accumulations of copper in children with ICT have been attributed primarily to an increased dietary intake of copper. However, 64 124 child-year exposures of children under the age of 6 y to drinking water containing a copper concentration of 125.9 mumol/L (8 mg/L) produced no deaths from any form of liver disease. Moreover, the ICT of seven infants was attributed primarily to drinking water containing < 110.2 mumol Cu/L (7 mg/L) despite evidence of the presence of a genetic defect in three of the patients, one of whom was exclusively breast- fed. These data suggest that ICT cannot be caused solely by increased dietary intake of copper and occurs only in children with an unidentified genetic defect.",childhood cirrhosis;copper;liver injury;Wilson disease;copper metabolism;diet restriction;dietary intake;fever/si [Side Effect];human;idiopathic disease;intoxication;leukopenia/si [Side Effect];metabolic disorder;proteinuria/si [Side Effect];rash/si [Side Effect];review;thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];drinking water;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Scheinberg, I. H.;Sternlieb, I.",1996,May,,0,0,
2519,Metal-induced hepatotoxicity,"Figure 3 summarizes several proposed mechanisms of iron- or copper- induced hepatotoxicity. It has long been suspected that free radicals may play a role in iron- and copper-induced cell toxicity because of the powerful prooxidant action of iron and copper salts in vitro. In the presence of available cellular reductants, iron or copper in low molecular weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates, resulting in wide-ranging impairment in cellular function and integrity. However, cells are endowed with cytoprotective mechanisms (antioxidants, scavenging enzymes, repair processes) that act to counteract the effects of free radical production. Thus, the net effect of metal-induced free radicals on cellular function will depend on the balance between radical production and the cytoprotective systems. As a result, there may be a rate of free radical production that must be exceeded before cellular injury occurs. Evidence has now accumulated that iron or copper overload in experimental animals can result in oxidative damage to lipids in vivo, once the concentration of the metal exceeds a threshold level. In the liver, this lipid peroxidation is associated with impairment of membrane dependent functions of mitochondria (oxidative metabolism) and lysosomes (membrane integrity, fluidity, pH). Although these findings do not prove causality, it seems likely that lipid peroxidation is involved, since similar functional defects are produced by metal-induced lipid peroxidation in these organelles in vitro. Both iron and copper overload impair hepatic mitochondrial respiration, primarily through a decrease in cytochrome c oxidase activity. In iron overload, hepatocellular calcium homeostasis may be impaired through damage to mitochondrial and microsomal calcium sequestration. DNA has also been reported to he a target of metal-induced damage in the liver; this may have consequences as regards malignant transformation. The levels of some antioxidants in the liver are decreased in rats with iron or copper overload, which is also suggestive of ongoing oxidative stress. Reduced cellular ATP levels, lysosomal fragility, impaired cellular calcium homeostasis, and damage to DNA may all contribute to hepatocellular injury in iron and copper overload. There are few data addressing the key issue of whether tree radical production is increased in patients with iron or copper overload. Patients with hereditary hemochromatosis have elevated plasma levels of TBA-reactants and increased hepatic levels of MDA-protein and HNE-protein adducts, indicative of lipid peroxidation. Mitochondria isolated from the livers of Wilson disease patients have evidence of lipid peroxidation, and some patients with Wilson disease have decreased hepatic and plasma levels of vitamin E. Additional investigation will be required to fully assess oxidant stress and its potential pathophysiologic role in patients with iron or copper overload.",DNA damage;endoplasmic reticulum;enzyme activity;gene;hemochromatosis/di [Diagnosis];human;iron overload/co [Complication];iron overload/di [Diagnosis];iron overload/et [Etiology];iron overload/th [Therapy];lipid peroxidation;liver cell carcinoma/co [Complication];liver cell carcinoma/et [Etiology];liver cell membrane;liver lysosome;liver mitochondrion;liver toxicity/et [Etiology];nonhuman;oxidative stress;priority journal;review;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];8 hydroxydeoxyguanosine/ec [Endogenous Compound];acid phosphatase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkadiene;alpha tocopherol/ec [Endogenous Compound];aminopyrine n demethylase/ec [Endogenous Compound];antioxidant/ec [Endogenous Compound];ascorbic acid/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/to [Drug Toxicity];cytochrome P450/ec [Endogenous Compound];DNA/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];free radical/to [Drug Toxicity];glutathione/ec [Endogenous Compound];hemosiderin/ec [Endogenous Compound];hydrogen peroxide/to [Drug Toxicity];hydroxyl radical/to [Drug Toxicity];iron/to [Drug Toxicity];iron chelate;iron dextran;lipid/ec [Endogenous Compound];lipid hydroperoxide/to [Drug Toxicity];malonaldehyde;metallothionein/ec [Endogenous Compound];n acetyl beta glucosaminidase/ec [Endogenous Compound];penicillamine;thiobarbituric acid reactive substance;transferrin/ec [Endogenous Compound];unindexed drug,"Britton, R. S.",1996,,,0,0,
2520,Pleural effusion associated with D-penicillamine therapy: A case report,This case report illustrates the occurrence of a large pleural effusion associated with long-term D-penicillamine therapy. This complication has not previously been reported.,adult;article;case report;female;Goodpasture syndrome/si [Side Effect];human;pleura effusion/si [Side Effect];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Karkos, C.;Moore, A.;Manche, A.;Thorpe, J. A. C.",1996,,,0,0,
2521,Inhibition of hereditary hepatitis and liver tumor development in Long- Evans cinnamon rats by the copper-chelating agent trientine dihydrochloride,"Trientine dihydrochloride (trientine) is an alternative medicinal copper chelating agent for patients with Wilson's disease of penicillamine intolerance. We examined the effects of trientine on the spontaneous development of hepatitis and hepatic tumors, by its short-term and long-term administration to Long. Evans cinnamon (LEC) rats with an accumulation of copper in the liver, as animal models of Wilson's disease. Male rats were given trientine in their drinking water at 1500 ppm for 18 weeks, from 6 weeks to 24 weeks of age in short-term experiment, and 1500 pore for 27 weeks then 750 ppm for 52 weeks, from 8 to 87 weeks of age in the long-term experiment. Development of hepatitis was observed in the control LEC rats at 18 weeks of age. They had high levels of plasma transaminases (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase [GPT]), and on pathological examination, hepatocyte destruction was observed. Histological findings revealed that short-term administration of trientine inhibited the development of hepatitis remarkably. The plasma GOT and GPT levels of treated animals were only slightly higher than those of normal LEA (Long-Evans with agouti coat color) rats, a sibling line of LEC rats. Copper levels in the liver were decreased by a maximum of 50%. In the long-term administration of trientine, the incidence of hepatic cell carcinoma (HCC) in the treated rats was 67% that of the untreated LEC rats, and the number of HCCs per rat in the treated group was 0.7 +/- 0.5, being significantly lower as compared with 4.7 +/- 3.5 in the untreated rats. Additionally, the development of cholangiofibrosis in LEC rats was completely prevented by long-term administration of the agent. The copper level in the liver of treated rats was reduced by 33% at 87 weeks of age. Development of HCC in LEC rats might be partly, but not totally, because of copper accumulation. No effects on the levels of copper, iron, or zinc in the liver of LEA rats was detected, and no adverse effects were detected in either LEC or LEA rats after both short- and long-term administration of trientine in drinking water.",animal model;animal tissue;article;chelation;controlled study;genetic disorder/co [Complication];genetic disorder/pc [Prevention];hepatitis/co [Complication];hepatitis/pc [Prevention];liver cell carcinoma/et [Etiology];liver cell carcinoma/pc [Prevention];liver failure/co [Complication];liver failure/pc [Prevention];liver function test;liver weight;male;nonhuman;oral drug administration;priority journal;rat;treatment outcome;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];chelating agent/ad [Drug Administration];chelating agent/dt [Drug Therapy];copper/to [Drug Toxicity];drinking water;iron;liver enzyme/ec [Endogenous Compound];trientine/ad [Drug Administration];trientine/dt [Drug Therapy];zinc,"Sone, H.;Maeda, M.;Wakabayashi, K.;Takeichi, N.;Mori, M.;Sugimura, T.;Nagao, M.",1996,,http://dx.doi.org/10.1053/jhep.1996.v23.pm0008666330,0,0,
2522,Cranial MR imaging in Wilson's disease,"OBJECTIVE. The purpose of the study was to describe the range of abnormalities seen on cranial MR images of patients with Wilson's disease and correlate the findings with clinical severity, duration of disease, and duration of neurologic signs and symptoms before treatment. In those patients with serial studies, the changes on MR images were compared with the clinical response. SUBJECTS AND METHODS. Twenty-five patients with Wilson's disease underwent MR imaging of the brain using conventional spin-echo sequences (n = 25), phase maps (n = 8), and partially refocused interleaved multiple-echo sequences (n = 5). RESULTS. MR imaging findings were abnormal in 22 patients and normal in three patients. The basal ganglia were interpreted as abnormal in 19 (86%) of 22 patients, involving the putamen in 19 (86%), the thalami in 12 (54%), the caudate head in 10 (45%), and the globus pallidus in nine (41%). We found a predilection for involvement of the outer rim of the putamen and the ventral nuclear mass of the thalami. The claustrum was abnormal in three patients. The midbrain was abnormal in 17 (77%) of these 22 patients, affecting predominantly the tegmentum but also the substantia nigra, red nuclei, inferior tectum, and crura. The pons was abnormal in 18 (82%) of 22 patients, and the cerebellum was abnormal in 11 patients (50%), with involvement of the superior middle cerebellar peduncles. Atrophy was present in 18 (82%) of 22 patients, and cortical white matter changes were apparent in 13 (59%) of 22 patients. The scan of one untreated patient revealed shortening of the T1 relaxation time in the thalami, which was consistent with the paramagnetic effects of copper. Phase maps and partially refocused interleaved multiple-echo sequences performed in eight and five patients, respectively, and used to reveal a susceptibility change induced by iron or copper showed normal findings. We found a significance inverse relationship between severity, but not extent, of change in signal intensity and the length of untreated disease (p = .030) and the total duration of disease (p = .015). The study group was too small to show a correlation with clinical findings. Changes seen on MR images matched the clinical response to treatment in only two of the seven patients who underwent follow-up studies. CONCLUSION. MR imaging revealed abnormalities in the basal ganglia, cerebral white matter, midbrain, pons, and cerebellum. The paramagnetic effects of copper were detected only in untreated patients. Patients with a longer duration of disease had less severe changes in signal intensity. MR imaging was of limited value in follow-up.",adolescent;adult;article;brain;child;clinical article;disease severity;female;human;male;nuclear magnetic resonance imaging;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"King, A. D.;Walshe, J. M.;Kendall, B. E.;Chinn, R. J. S.;Paley, M. N. J.;Wilkinson, I. D.;Halligan, S.;Hall-Craggs, M. A.",1996,,,0,0,
2523,Other rheumatological complications of GI disorders [8],,arthropathy/co [Complication];arthropathy/dt [Drug Therapy];bone cyst/co [Complication];bone necrosis/co [Complication];clinical feature;Crohn disease;gastrointestinal disease;human;joint hypermobility/co [Complication];letter;osteoarthritis/co [Complication];osteomalacia/co [Complication];osteoporosis/co [Complication];priority journal;rheumatology;Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Monkemuller, K. E.;Martin, R.",1996,,,0,0,
2524,How to treat Wilson's disease. [French],,article;drug effect;drug efficacy;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Benhamou, J. P.",1996,,,0,0,
2525,Wilson disease: Asymptomatic or late-onset type? [2],,Chinese herb/dt [Drug Therapy];human;letter;liver cirrhosis;liver function;Wilson disease/dt [Drug Therapy];gluconate zinc/dt [Drug Therapy];succimer/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Wang, X. P.;Hefter, H.",1996,,,0,0,
2526,A Wilson's disease patient with prominent cerebral white matter lesions: Five-year follow-up by MRI,,adult;article;basal ganglion;case report;copper blood level;focal epilepsy/dt [Drug Therapy];follow up;human;liver function;male;nuclear magnetic resonance imaging;pathogenesis;priority journal;tremor/cn [Congenital Disorder];tremor/di [Diagnosis];tremor/et [Etiology];white matter;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];valproic acid/dt [Drug Therapy],"Yoshii, F.;Takahashi, W.;Shinohara, Y.",1996,,,0,0,
2527,Successful medical treatment of severely decompensated Wilson disease,"Delayed response to medical treatment sometimes leads to unnecessary liver transplantation in patients with severely decompensated Wilson disease. We report the course of five patients (mean age 13.4 years, range 11 to 15 years) with severely decompensated Wilson disease who were successfully treated medically. Prothrombin time improved after a minimum of 1 month and returned to normal within 3 months to 1 year or more.",adolescent;article;child;clinical article;female;human;liver failure/co [Complication];liver failure/di [Diagnosis];liver transplantation;male;neutropenia/di [Diagnosis];neutropenia/si [Side Effect];plasmapheresis;priority journal;prothrombin time;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;hemoglobin/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];prothrombin/ec [Endogenous Compound];trientine/do [Drug Dose];trientine/dt [Drug Therapy];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy],"Silva, E. E. S.;Sarles, J.;Buts, J. P.;Sokal, E. M.",1996,,http://dx.doi.org/10.1016/S0022-3476%2896%2970412-2,0,1,
2528,Wilson's disease. [German],,human;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];ceruloplasmin/ec [Endogenous Compound];dimercaprol;penicillamine;trientine,"Propst, T.;Propst, A.;Judmaier, G.;Vogel, W.",1996,,,0,0,
2529,Mechanisms of selective copper removal by tetrathiomolybdate from metallothionein in LEC rats,"Copper (Cu) was selectively removed from metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color) in vivo and in vitro by tetrathiomolybdate (TTM). Female LEC rats were injected intraperitoneally with TTM at a dose of 10 mg/kg body weight for 8 consecutive days. More than 2/3 of the Cu accumulating in the liver was removed by TTM treatment 24 h after the last injection. Although most Cu was bound to MT in the soluble fraction before TTM treatment, the Cu remaining in the liver was present almost exclusively in the non-soluble fraction together with molybdenum (Mo). Cu,Zn,Cd-MT was separated from the liver of LEC rats that had been injected with cadmium (Cd) and reacted with TTM at mol ratios of 0, 0.25, 0.50, 1.0, 2.0 and 4.0 to Cu bound to MT for 10 min at 37degreeC. When TTM was added at a mol ratio of less than 1.0, a Cu,Zn,Cd-MT/TTM complex was detected, while addition of TTM at a mol ratio of greater than 1.0 selectively removed Cu from MT and produced a Cu/TTM complex via liberation of Zn,Cd-MT from the Cu,Zn,Cd-MT/TTM complex. Excessive TTM appeared to facilitate polymerization of the Cu/TTM complex to insoluble polymers. The dose-related formation of differing MT/TTM complexes explains the findings observed in vivo.",Chelation therapy;Copper;hplc/icp-ms;LEC rat;Metallothionein;Tetrathiomolybdate;Wilson disease;animal model;article;controlled study;copper metabolism;female;liver;nonhuman;priority journal;rat;Wilson disease/dt [Drug Therapy];copper/to [Drug Toxicity];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology],"Ogra, Y.;Ohmichi, M.;Suzuki, K. T.",1996,08 Jan,http://dx.doi.org/10.1016/0300-483X%2895%2903171-B,0,0,
2530,Essential trace element and skin diseases. [Japanese],"We have described herein various skin diseases which are caused by essential trace element deposition, deficiency, allergy, etc. Pigmentation of hemochromatosis and hemosiderosis are recognized by hemosiderin deposition in the dermis. Acrodermatitis enteropathica is caused by a deficiency of Zn and is classified as either a hereditary type or as an acquired type. The former is autosomal recessive and the latter is caused by a low intake of Zn. Wilson's disease and Menkes' kinky hair syndrome, which are caused by abnormal Cu metabolism, elicit hyperpigmentation and morphological changes of the hair, respectively. It appears that kinky hair formation results from low activity of sulfhydryl oxidase which is a Cu enzyme. Bowen disease, which is carcinoma in situ, is caused by As toxicosis. Some cases, such as palmo-plantar-pustulosis, lichen planus and oral lichen planus are caused by allergies to metals used in dental surgery, especially Ni, Co, Cr and Sn.",Bowen disease/et [Etiology];human;Menkes syndrome/et [Etiology];metabolism;review;skin disease/et [Etiology];trace element,"Yamada, H.;Ogawa, H.",1996,Jan,,0,0,
2531,Treatment of Wilson's disease: The historical background,,history of medicine;human;priority journal;prognosis;short survey;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];unithiol/dt [Drug Therapy],"Walshe, J. M.",1996,,,0,0,
2532,Chelators in biomedical research: A review,"Chelators have been used in many aspects of biomedical research, from water softening to antidotes for heavy metal ion intoxication. At present, novel therapeutic regimens have been developed against psychiatric disorders, viral, and protozoal infections. Many clinical trials and biomedical research continues in the use of chelating agents in solving various medical problems.",carcinogenicity;drug indication;human;infection;intoxication;mental disease;mutagenicity;nonhuman;review;side effect;Wilson disease;2 furildioxime/pd [Pharmacology];antidote;chelating agent/ae [Adverse Drug Reaction];chelating agent/to [Drug Toxicity];chelating agent/pd [Pharmacology];crown ether/pd [Pharmacology];cyclohexanediaminetetraacetic acid/pd [Pharmacology];deferoxamine/ae [Adverse Drug Reaction];deferoxamine/to [Drug Toxicity];deferoxamine/pd [Pharmacology];deferriferrithiocin/pd [Pharmacology];diethyldithiocarbamic acid/pd [Pharmacology];dimercaprol/pd [Pharmacology];edetic acid/pd [Pharmacology];heavy metal/to [Drug Toxicity];iron/to [Drug Toxicity];lead/to [Drug Toxicity];manganese/to [Drug Toxicity];nitrilotriacetic acid/pd [Pharmacology];penicillamine/pd [Pharmacology];pentetic acid/pd [Pharmacology];razoxane/pd [Pharmacology];succimer/pd [Pharmacology];unclassified drug,"Mbati, P. A.",1996,,,0,0,
2533,Pharmacokinetics of tetrathiomolybdate in LEC and normal rats,,animal model;animal tissue;conference paper;controlled study;copper metabolism;drug liver level;drug mechanism;drug uptake;intraperitoneal drug administration;nonhuman;rat;Wilson disease/cn [Congenital Disorder];Wilson disease/et [Etiology];copper/pk [Pharmacokinetics];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology],"Ogra, Y.;Ohmichi, M.;Suzuki, K. T.",1996,,,0,0,
2534,Excess zinc associated with severe progressive cholestasis in Cree and Ojibwa-Cree children,"Background. High hepatic copper concentrations have been reported in several liver disorders. We report six Native Canadian children with severe chronic cholestatic liver disease, who had excess hepatic copper and zinc. Methods. The children, aged 22 months to 8 years, came from northern Ontario, Canada. All were referred for possible liver transplantation because of end-stage liver disease. We examined explanted liver samples (or liver biopsy material in one case) by scanning transmission electronmicroscopic (STEM) X-ray elemental microanalysis and atomic absorption spectrophotometry. Samples from four controls (two with no liver pathology, one with biliary atresia, and one with Wilson's disease) were also analysed by atomic absorption spectrophotometry. Findings. The explanted livers showed similar distinctive signs of advanced biliary cirrhosis, and on electronmicroscopy there were dense deposits in enlarged lysosomes and in cytoplasm. Hepatic copper concentrations were many times higher in the five patients with measurements (47.6-56.9 mug/g dry weight) than in two samples of normal control liver tissue (2.3 and 2.9 mug/g). Similarly, hepatic zinc concentrations were many times higher in the patients than in controls (104-128 vs 1.9-3.2 mug/g dry weight). Interpretation. The excess copper may be due to chronic cholestasis but the excess zinc is unexplained. Since three of the patients are related (shared grandparents), a genetic disorder of metal metabolism is possible, but we cannot exclude environmental factors.",article;atomic absorption spectrometry;Canada;child;cholestasis/et [Etiology];clinical article;controlled study;cytoplasm;environmental factor;female;human;human tissue;Indian;liver biopsy;liver level;liver lysosome;liver transplantation;male;microanalysis;priority journal;scanning electron microscopy;transmission electron microscopy;copper/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Phillips, M. J.;Ackerley, C. A.;Superina, R. A.;Roberts, E. A.;Filler, R. M.;Levy, G. A.",1996,30 Mar,http://dx.doi.org/10.1016/S0140-6736%2896%2991347-1,0,0,
2535,Neurological impairment and recovery in Wilson's disease: Evidence from PET and MRI,"We studied the relationship of regional cerebral glucose consumption (rCMRGlc) and striatal dopamine D2 receptor binding as assessed with positron emission tomography (PET) with the structural abnormalities of the brain in magnetic resonance images (MR), and the degree of neurological impairment in 18 patients with Wilson's disease (WD). The rCMRGlc was determined in the, basal ganglia, the thalamus, the cerebral cortex, and the cerebellar hemispheres. The severity of neurological signs, defined by semiquantitative motor impairment scores, correlated highly (r = -0.80) with the reduction of striatal rCMRGlc. Clinical. scores, striatal rCMRGlc, and the degree of MRI abnormalities showed no correlation with different indices of dopamine D2 receptor binding. Sequential PET measurements in three patients during treatment with chelating agents revealed a moderate increase of striatal rCMRGlc (in two patients) and a moderate to marked increase of striatal D2 receptor binding (in three patients) in association with clinical improvement. Our data suggest that the rCMRGlc represents a sensitive and objective measure for assessing and monitoring striatal and extrastriatal involvement in WD. The lack of correlation between the dopamine D2 receptor binding and striatal rCMRGlc and structural abnormalities may be explained by the wide spectrum of clinical manifestations and different responses to treatment in WD patients.",Dopamine D2 receptor;Magnetic resonance imaging;Positron emission tomography;Regional cerebral glucose metabolism;Wilson's disease;adult;article;brain region;clinical article;controlled study;female;glucose utilization;human;male;nuclear magnetic resonance imaging;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];dopamine 2 receptor/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Schlaug, G.;Hefter, H.;Engelbrecht, V.;Kuwert, T.;Arnold, S.;Stocklin, G.;Seitz, R. J.",1996,,http://dx.doi.org/10.1016/0022-510X%2895%2900293-B,0,1,
2536,Bacterial resistances to toxic metal ions - A review,"Bacterial plasmids encode resistance systems for toxic metal ions, including Ag<sup>+</sup>, AsO<inf>2</inf><sup>-</sup>, AsO<inf>4</inf><sup>3-</sup>, Cd<sup>2+</sup>, Co<sup>2+</sup>, CrO<inf>4</inf><sup>2-</sup>, Cu<sup>2+</sup>, Hg<sup>2+</sup>, Ni<sup>2+</sup>, Pb<sup>2+</sup>, Sb<sup>3+</sup>, TeO<inf>3</inf><sup>2-</sup>, Tl<sup>+</sup> and Zn<sup>2+</sup>. The function of most resistance systems is based on the energy-dependent efflux of toxic ions. Some of the efflux systems are ATPases and others are chemiosmotic cation/proton antiporters. The Cd<sup>2+</sup>-resistance ATPase of Gram-positive bacteria (CadA) is membrane cation pump homologous with other bacterial, animal and plant P-type ATPases. CadA has been labeled with <sup>32</sup>P from [alpha-<sup>32</sup>P]ATP and drives ATP-dependent Cd<sup>2+</sup> (and Zn<sup>2+</sup>) uptake by inside-out membrane vesicles (equivalent to efflux from whole cells). Recently, isolated genes defective in the human hereditary diseases of copper metabolism, namely Menkes syndrome and Wilson's disease, encode P-type ATPases that are more similar to bacterial CadA than to other ATPases from eukaryotes. The arsenic resistance efflux system transports arsenite [As(III)], alternatively using either a double-polypeptide (ArsA and ArsB) ATPase or a single-polypeptide (ArsB) functioning as a chemiosmotic transporter. The third gene in the arsenic resistance system, arsC, encodes an enzyme that converts intracellular arsenate [As(V)] to arsenite [As(III)], the substrate of the efflux system. The triple-polypeptide Czc (Cd<sup>2+</sup>, Zn<sup>2+</sup> and Co<sup>2+</sup>) chemiosmotic efflux pump consists of inner membrane (CzcA), outer membrane (CzcC) and membrane-spanning (CzcB) proteins that together transport cations from the cytoplasm across the periplasmic space to the outside of the cell.",Antiporter;Arsenic;Bacterial plasmids;Cadmium;Efflux;Menkes syndrome;Mercury;bacterial genetics;cation transport;cell membrane transport;copper metabolism;cyanobacterium;drug resistance;Enterococcus;eukaryote;Gram negative bacterium;Gram positive bacterium;ion transport;isotope labeling;membrane vesicle;Menkes syndrome/cn [Congenital Disorder];nonhuman;plasmid;priority journal;protein expression;review;soil microflora;Wilson disease/cn [Congenital Disorder];adenosine triphosphatase/ec [Endogenous Compound];antimony;antiporter/ec [Endogenous Compound];arsenic acid;arsenic trioxide;cation/ec [Endogenous Compound];chromic acid;cobalt;copper ion;heavy metal;lead;nickel;silver;tellurium derivative;thallium;toxic substance;zinc,"Silver, S.",1996,07 Nov,http://dx.doi.org/10.1016/S0378-1119%2896%2900323-X,0,0,
2537,Clinical analysis and short-term effect of hepatolenticular degeneration. [Chinese],"24 patients with hepatolenticular degeneration were separately administered D-penicillamine or zinc sulfate for a short period. Symptoms were markedly improved in two groups, copper oxidase before leaving hospital was significantly increased than that after admission (P < 0.05). The author considers that zinc sulfate has more advantages such as safety, low price, less toxic side effects than D-penicillamine.",hepatolenticular degeneration/TH;penicillamine/TU;zinc/TU;article;clinical article;drug cost;drug effect;drug safety;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Hu, Z.;Hu, C.;Liu, Z.",1996,,,0,0,
2538,A comparison of efficacy and urinary copper excretion in the treatment of hepatolenticular degeneration with penicillamine and zinc. [Chinese],Purpose: To compare the efficacy and urinary copper excretion in the treatment of hepatolenticular degeneration (HLD) with penicillamine and zinc. Methods: The outputs of urinary copper were measured by anodic stripping voltammetry method. Data were analyzed with chi<sup>2</sup> test and t test. Results: Sixty-nine patients with HLD treated with penicillamine and zinc has been reported. Mean courses of treatment with penicillamine were 10.25 +/- 3.84 years and the effective rate was 94.2%. Mean courses of treatment with zinc were 3.62 +/- 0.94 years and the effective rate was 58.8%. At the same time the outputs of urinary copper of the group treated with penicillamine were higher obviously than the group treated with zinc (P < 0.01). Conclusions: The efficacy of treatment with penicillamine was superior to zinc therapy. Penicillamine may be more effective in getting rid of excessive free copper of tissues than zinc.,hepatolenticular degeneration;penicillamine;urinary copper;zinc;article;clinical trial;controlled clinical trial;controlled study;drug efficacy;human;major clinical study;oral drug administration;potentiometry;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/ct [Clinical Trial];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cm [Drug Comparison];zinc/dt [Drug Therapy],"Li, N.;Yao, J.;Lu, C.;Xia, B.;Chen, X.",1996,,,0,0,
2539,Inherited liver diseases affecting the adult,"A variety of different inherited disorders may cause liver disease in adults. Recent advances in molecular genetics have improved our understanding of these diseases, such as the isolation and characterization of the genes responsible for Wilson disease, alpha<inf>1</inf>-antitrypsin deficiency, and cystic fibrosis. A candidate gene responsible for hereditary hemochromatosis has also recently been cloned. These scientific advances have important implications in the diagnosis, treatment, and screening of patients with genetic diseases and their families. We review the most common inherited liver diseases affecting adults, with emphasis on the clinical implications of recent molecular advances.",alpha antitrypsin deficiency/di [Diagnosis];alpha antitrypsin deficiency/ep [Epidemiology];alpha antitrypsin deficiency/et [Etiology];alpha antitrypsin deficiency/th [Therapy];autosomal dominant disorder;clinical feature;cystic fibrosis/di [Diagnosis];cystic fibrosis/dt [Drug Therapy];cystic fibrosis/ep [Epidemiology];cystic fibrosis/et [Etiology];cystic fibrosis/th [Therapy];gene therapy;hemochromatosis/di [Diagnosis];hemochromatosis/ep [Epidemiology];hemochromatosis/et [Etiology];hemochromatosis/su [Surgery];human;inheritance;kidney polycystic disease/di [Diagnosis];kidney polycystic disease/su [Surgery];liver disease;liver transplantation;pathophysiology;priority journal;review;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Tung, B. Y.;Kowdley, K. V.",1996,,,0,0,
2540,MRI and PET in Wilson's disease: Clinico-radiological correlation [2],,case report;human;letter;nuclear magnetic resonance imaging;positron emission tomography;priority journal;Wilson disease/di [Diagnosis];trientine,"Ikeda, K.;Kinoshita, M.;Nemoto, H.;Sunohara, N.;Seitz, R.",1996,,http://dx.doi.org/10.1016/S0022-510X%2896%2900278-X,0,0,
2541,Hirsutism and macromastia in a girl treated with Penicillamine for Wilson's Disease. [German],"In an 11 8/12 year old girl hirsutism dark long facial hair and macromastia developed about 3 months after starting treatment with Penicillamine for Wilson's Disease. The patient had regular menses. Numerous endocrinological investigations showed no abnormalities responsible for hirsutism and macromastia. After finishing therapy with Penicillamine the hirsutism disappeared after a few months. The size and tension of the mammae decreased markedly, too.",hirsutism;macromastia;Penicillamine;Wilson's disease;article;breast hypertrophy/et [Etiology];breast hypertrophy/si [Side Effect];case report;endocrine system examination;female;hirsutism/et [Etiology];hirsutism/si [Side Effect];human;preschool child;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Willgerodt, H.;Keller, E.",1996,February,,0,0,
2542,Hepatology: hepatocellular diseases. [French],"Three topics for 1995 will be treated: 1) Hemochromatosis is a frequent disease, easy to screen and which can be treated by phlebotomy. Recent studies have shown that a large scale screening of the general population is effective in terms of public health care. 2) Genetic analysis of the molecular defect of Wilson's disease has progressed considerably in 1995. More than 20 mutations have been identified. Diagnosis of this disease, which is treatable by chelation, should be soon available with genetic methods. 3) Diagnosis of alcoholic hepatitis is made by histology. In its severe forms corticotherapy improves survival.",alcohol liver disease/di [Diagnosis];alcohol liver disease/dt [Drug Therapy];genetic analysis;hemochromatosis/ep [Epidemiology];hemochromatosis/et [Etiology];human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/ep [Epidemiology];liver disease/et [Etiology];liver disease/su [Surgery];mass screening;short survey;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy],"Frossard, J. L.;Giostra, E.;Margalith, D.;Gonvers, J. J.;Hadengue, A.",1996,,,0,0,
2543,Prospective study on intelligence quotient of 28 hepatic lenticular degeneration patients with treatment combining traditional Chinese and Western medicine. [Chinese],"Intelligence quotient (IQ) of 28 hepatic lenticular degeneration (HLD) patients was analysed with Wechsler Adult Intelligence Scale-revised by China (WAIS-RC) before and after two months treatment by the HLD-Relief decoction supplemented with copper-clearing drug, and the result was compared with that of 30 healthy persons for control. The results showed that the Vocable IQ (VIQ), Performance IQ(PIQ) and Full IQ(FIQ) of HLD patients were markedly lower than that of control (P < 0.005), especially in visual space disorder, which indicated that the copper ion depositing in patient's brain not only damaged neuronic motorial functions but also produced a marked effect on the patient's intelligence. After treatment, the total intelligential level including VIQ, PIQ and FIQ has been raised, particularly in PIQ in which all scores were obviously increased (P < 0.001). It was also showed that the damage of intelligence in HLD patient became more serious as the course of disease was prolonged and the early treatment facilitated the IQ level to approach the normal criterion. It indicated that the treatment with combined therapy is effective to the intelligence and extrapyramidal symptoms in HLD patients.",adolescent;adult;article;drug combination;drug effect;female;human;intelligence;male;prospective study;psychological aspect;Wechsler intelligence scale;Wilson disease/dt [Drug Therapy];chelating agent/ad [Drug Administration];herbaceous agent/ad [Drug Administration];penicillamine/ad [Drug Administration];succimer/ad [Drug Administration],"Cai, Y. L.;Yang, R. M.;Xu, S. H.",1996,Jan,,0,0,
2544,"Disposition behavior and absorption mechanism of trientine, an orphan drug for Wilson's disease. [Japanese]","The disposition behavior of trientine, a selective copper-chelating drug for Wilson's disease, and its metabolites in normal patients with Wilson's disease and rats were studied. A high concentration of metabolites appeared in blood samples of patients and rats in the early stage after administration of trientine. Furthermore, large amount of trientine metabolites were excreted into the urine of patients. These results suggest that trientine is remarkably subjected to a first-pass effect. The drug concentration area under the curve (AUC) of the unchanged form and the metabolites of trientine in patients was not dependent on the administered dosage. It seems that the absorption process is an important factor for the disposition behavior of trientine, we have also investigated the uptake characteristics of trientine by rat intestinal brush-border membrane vesicles. The uptake characteristics of trientine were similar to the physiological polyamines, spermine and spermidine. The uptake rate of trientine was dose-dependently inhibited by spermine and spermidine. Moreover, spermine competitively inhibited the uptake of trientine with a Ki value of 18.6 muM. This value is very close to the Km value for spermine (30.4 muM). These data suggested that the uptake mechanism of trientine in rat small intestinal brush-border membrane vesicles was almost identical to that of spermine and spermidine, and that the physiological polyamines seem to have the ability to inhibit the absorption of trientine from the gastrointestinal tract.",animal;article;child;female;human;intestine;intestine absorption;male;metabolism;microvillus;rat;tissue distribution;Wilson disease/dt [Drug Therapy];Wistar rat;chelating agent/dt [Drug Therapy];chelating agent/pk [Pharmacokinetics];polyamine/pk [Pharmacokinetics];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics],"Tanabe, R.",1996,Mar,,0,0,
2545,Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and F344 rats,"Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a chelating agent used to treat Wilson's disease patients who are intolerant of the drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats. Mice and rats received trien-2HCl in the drinking water at concentrations of 0, 120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN-76A) diet, both containing nutritionally adequate levels of copper. An additional control group of rats and mice received a Cu-deficient AIN-76A diet. This low copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell proliferation, and increased heart weight, together with undetectable levels of plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels somewhat (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation of the lung interstitium and liver periportal fatty infiltration were seen in both sexes, and hematopoietic cell proliferation was seen in the spleen of males. Kidney and body weights were reduced in males as was the incidence of renal cytoplasmic vacuolization. There were no signs of copper deficiency in mice exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31 diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm.",anemia;article;chronic toxicity;copper blood level;copper deficiency;cytomegaly;female;male;mouse;nonhuman;oral drug administration;rat;uterus;copper;trientine/to [Drug Toxicity],"Greenman, D. L.;Morrissey, R. L.;Blakemore, W.;Crowell, J.;Siitonen, P.;Felton, P.;Allen, R.;Cronin, G.",1996,,http://dx.doi.org/10.1006/faat.1996.0020,0,0,
2546,"Aggressive behavior, increasing loss of independence in mentally retarded patient. [German]","Morbus Wilson is a rare autosomal recessive inborn error of metabolism which leads to an excessive deposition of copper many tissues. There are three types of presentation, an asymptomatic, a hepatic and a neurologic one. In this case report we present a 24-year-old man with mental retardation who showed changes in behaviour and slowness. Clinical and laboratory investigations confirmed the diagnosis of Morbus Wilson. We briefly review typical aspects of this rare disease.",adult;article;behavior;case report;clinical observation;clinical study;diagnosis;human;male;mental deficiency/et [Etiology];psychological aspect;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Dukas, L.;Vogt, M.",1996,21 May,,0,0,
2547,Wilson disease with HCV infection. [Polish],"In this paper we describe liver-related Wilson's disease in two sisters. The elder died of liver failure. Our patient, a 13-year-old girl has hepatitis C coinfection. Gradual improvement was observed after Cuprenil, Zincteral and interferon (Intron A).",hcv;Liver;Wilson's disease;adolescent;article;case report;female;hepatitis C/dt [Drug Therapy];human;liver failure;Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];recombinant alpha2b interferon/cb [Drug Combination];recombinant alpha2b interferon/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Nalecz, A.;Socha, J.;Czlonkowska, A.;Gajda, J.",1995,,,0,0,
2548,Molybdenum and copper kinetics after tetrathiomolybdate injection in LEC rats: Specific role of serum albumin,"Chelation therapy with tetrathiomolybdate (TTM) was applied to Long-Evans rats with a cinnamon coat-color (LEC rats), an animal model for Wilson disease, to remove copper (Cu) accumulated in the liver in a form bound to metallothionein (MT). Changes in molybdenum (Mo) and Cu concentrations and their biological forms in serum of LEC rats determined at different times after a single intraperitoneal injection were compared with those of Wistar (normal) rats. The change in Mo concentration in serum of normal rats was mono-phasic, whereas in LEC rats it was bi-phasic. The phase in normal rats and the first phase in LEC rats appeared to reflect the process of uptake and disappearance of TTM in the livers of Wistar and LEC rats. On the other hand, the second phase in LEC rats paralleled the changes of Cu and appeared to reflect the complex formation (Cu/thiomolybdate complex) between Mo and Cu accumulated in the liver. The complex was specifically bound to albumin as determined by high performance liquid chromatography with inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). The results suggested that the changes in the Mo concentration in serum reflected the amount of Cu in the liver.",Albumin;Copper disorder;hplc/icp-ms;LEC rat;Molybdenum;Tetrathiomolybdate;Thiomolybdate;Wilson disease;animal model;article;blood analysis;chelation therapy;controlled study;copper metabolism;drug protein binding;drug tissue level;intraperitoneal drug administration;liver;nonhuman;priority journal;Wilson disease/dt [Drug Therapy];albumin/ec [Endogenous Compound];copper/ec [Endogenous Compound];molybdenum/cr [Drug Concentration];molybdenum/pk [Pharmacokinetics];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pk [Pharmacokinetics],"Suzuki, K. T.;Ogra, Y.;Ohmichi, M.",1995,,,0,0,
2549,Systemic dispositions of molybdenum and copper after tetrathiomolybdate injection in LEC rats,"Mutant Long-Evans rats with a cinnamon coat-color (LEC rats) have been established as an animal model for Wilson disease, a genetic disorder of copper (Cu) metabolism. Systemic disposition of molybdenum (Mo) and altered distributions of Cu were compared in eight organs between LEC rats and Wistar rats (normal) at different times after a single intraperitoneal injection of tetrathiomolybdate (TTM) for chelation therapy. Excretion through urine and feces was also examined. Hepatic disposition of Mo was dramatically increased in LEC rats, suggesting that the interaction of TTM with Cu results in enhanced uptake of Mo. Concentrations of Mo and Cu decreased in the liver of LEC rats over time, whereas those in the spleen increased. Although the concentration of Mo taken up by the kidney decreased over time after an initial increase in both rats, Cu concentration increased over time. Cu was not redistributed to the brain. Excretion of Mo through urine was decreased and that into feces was increased in LEC rats compared with those in Wistar rats. These results indicate that TTM is taken up by the liver depending on the Cu content, and the Cu and Mo removed from the liver are mostly excreted through feces. Redistribution of Cu was observed in the spleen and kidneys, but not in the brain.",Copper disorder;icp-ms;LEC rat;Molybdenum;Tetrathiomolybdate;Thiomolybdate;Wilson disease;animal model;article;chelation therapy;controlled study;copper metabolism;drug feces level;drug tissue level;intraperitoneal drug administration;kidney;liver;nonhuman;priority journal;rat;spleen;urinalysis;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];molybdenum/cr [Drug Concentration];molybdenum/pk [Pharmacokinetics];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology],"Ogra, Y.;Ohmichi, M.;Suzuki, K. T.",1995,,,0,0,
2550,Haemolytic crisis with liver failure as initial manifestations of Wilson's disease. [German],"An 18-year-old woman developed an acute haemolytic anaemia, acute transient renal failure and progressive hepatic failure. Coeruloplasmin and serum copper concentration were normal; a Kayser-Fleischer ring and any neurological symptoms were absent initially. Liver biopsy was contraindicated because of increased bleeding tendency. Wilson's disease was diagnosed only after the acute renal failure had regressed, on the basis of the urinary copper excretion (2890 mug/d, rising to 7330 mug/d after D-penicillamine administration). Progressive liver failure required transplantation. After it the patient quickly recovered and is now, two years later, free of disease. This case demonstrates that Wilson's disease may be difficult to diagnose at the time of initial acute manifestation. But it can be recognized early from the pathognomonic low alkaline phosphatase and by calculation of free serum copper.",adult;article;case report;female;hemolytic anemia/dt [Drug Therapy];hemolytic anemia/et [Etiology];human;human tissue;kidney failure;liver failure/et [Etiology];liver failure/su [Surgery];liver transplantation;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Degenhardt, S.;Blomhard, G.;Hefter, H.;Kreuzpaintner, G.;Lindemann, W.;Lobeck, H.;Schnaith, E.;Stremmel, W.;Grabensee, B.",1994,,,0,0,
2551,Wilson's disease. [Croatian],"A 17-year-old girl with haemolytic anaemia, parenchymal livel disease and gallbladder calculi, is reported. Kayser-Fleischer rings, transaminasaemia, deficiency of ceruloplasmin, increased cupriuria, and nodular cirrhosis of the liver, confirmed the diagnosis of Wilson's disease. Penicillamine therapy had to be interrupted a short time after it was started, because of penicillamine-induces acute psychotic episode. Zinc-sulphate has controlled Wilson's disease in the patient.",adolescent;article;case report;female;human;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy],"Petrovic, M.;Bogunovic, M.;Jancic-Nedeljkov, R.;Covic, M.",1994,1994,,0,0,
2552,"Wilson's disease, IgA nephropathy and Henoch-Schonlein purpura: A casual association?. [French]","Background. IgA nephropathy may occur in adults with alcoholic cinrhosis. It has also been reported in children with alpha-1-antitrypsin deficiency. A case of IgA nephropathy associated with cirrhosis due to Wilson's disease is reported. Case report: A 10 year-old girl, was admitted for cirrhosis. She had suffered from ascitis and hematuria since the age of 6 years and vascular purpura since the age of 9 yr 6 mo. At admission, she had atrophic liver cirrhosis, ascitis splenomegaly and petechiae on her legs. There was microcytic anemia due to iron deficiency. The Coombs test was positive. There were hypoalbuminemia (2 g/dl) and polyclonal hyperglobulinemia (IgA 750 mg/dl, IgG 1670 mg/dl and IgM 250 mg/dl). Her serum concentrations of complement factors were normal and no immune complexes were detected in serum. She also showed biological changes due to kidney failure, hematuria and proteinuria. A liver biopsy showed micronodular cirrhosis with numerous plasma cells containing IgA. The search for an etiology showed ceruloplasmin levels of 5 mg/dl, elevated urinary copper excretion (> 150 mug/day) and above normal liver copper (255 mug/g dry weight); Kayser-Fleischer ring was also seen. The renal biopsy showed membranoproliferative glomerulonephritis, and immunofluorescent microscopy revealed C3 and IgA in the mesangial and subendothelial regions. The patient was given spironolactone and furosemide followed by triethylenetetramine dihydrochloride. Conclusions: The IgA nephropathy, vascular purpura and elevated serum IgA levels could be due to the liver changes. If so, they should be improved by a liver transplant, although our patient would be a better candidate for combined liver and kidney transplantation.",child;fibrosis;glomerulonephritis;hepatolenticular degeneration;IgA;purpura;anaphylactoid purpura;article;case report;disease association;female;human;immunoglobulin A nephropathy;kidney biopsy;liver biopsy;liver cirrhosis;priority journal;school child;Wilson disease/dt [Drug Therapy];trientine/dt [Drug Therapy],"Sarles, J.;Durand, J. M.;Scheiner, C.;Picon, G.",1993,,,0,0,
2553,Copper-associated liver disease in childhood,"Background/Aims: Indian childhood cirrhosis is associated with high liver copper concentrations and progressive liver disease with a high mortality. Early treatment with penicillamine was found to reduce mortality and reverse liver damage. We aimed to define the clinical features of copper-associated liver disease outwith the Indian subcontinent and encourage the earlier consideration of the syndrome in cryptogenic liver disease. Methods: Three European children presented between 10 and 29 months of age with abdominal distension, pyrexia and hepatosplenomegaly. Over 1-5 weeks their condition deteriorated rapidly due to liver failure. Two died within 2 months of onset and one received a successful liver transplant. In two cases consideration of the diagnosis occurred only on examination of the liver after orthotopic liver transplant or death. Light microscopy was used, with haematoxylin and eosin, reticulin and orcein stains. Tissue, plasma and water copper levels were measured by flame atomic absorption spectrometry. Results: All had micronodular cirrhosis and severe hepatocellular necrosis with Mallory bodies and copious-orcein positive material. Liver copper concentrations ranged from 1100-1310 mug/g dry weight. For two patients domestic water with high copper content had been used for the preparation of feeds. No environmental source of excess copper could be identified in the third case. Conclusions: We suggest that the above condition, which is called Indian childhood cirrhosis in the Indian subcontinent and Copper Storage Disease elsewhere, would be better named 'Copper-Associated Liver Disease in Childhood', emphasising the need to consider this disorder in unexplained liver disease and to seek possible sources of excessive copper intake.",Acute liver failure;Copper hepatotoxicity;Liver transplantation;abdominal distension;article;case report;childhood disease/dt [Drug Therapy];childhood disease/et [Etiology];Europe;fever;hepatosplenomegaly;histopathology;human;India;infant;liver disease/dt [Drug Therapy];liver disease/et [Etiology];liver failure/et [Etiology];liver failure/su [Surgery];mortality;preschool child;priority journal;copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Baker, A.;Gormally, S.;Saxena, R.;Baldwin, D.;Drumm, B.;Bonham, J.;Portmann, B.;Mowat, A. P.",1995,,http://dx.doi.org/10.1016/0168-8278%2895%2980059-X,0,0,
2554,Usefulness of Scheimpflug photography to follow up Wilson's disease,"A 24-year old female with ocular changes (Kayser-Fleischer ring and sunflower cataract) indicating Wilson's disease was followed up from 9 years of age with anterior eye segment image documentation by Scheimpflug photography. A low copper diet and systemic D-penicillamine were administered after the initial diagnosis of Wilson's disease. During a 15-year follow-up period, the yellowish/brown-colored granular opacification on the anterior lens capsule and/or in the capsule has mostly disappeared and instead, the same type of opacification has emerged on the posterior lens capsule, showing rather progressive changes compared with the initial findings. These changes which had developed in the lens during the past 15 years were difficult to detect by slit lamp examination alone, but they were clearly revealed by Scheimpflug slit images. To our knowledge this is the first case report on ocular changes disclosed through the application of a newly developed anterior eye segment examination. Ergo, Scheimpflug photography is valuable for follow-up studies of ocular complications seen in patients with Wilson's disease.",Copper deposits;Kayser-Fleischer ring;Scheimpflug photography;Sun flower cataract;Wilson's disease;adult;anterior eye segment;article;case report;cataract;female;follow up;human;lens capsule;photography;priority journal;slit lamp;Wilson disease;copper;penicillamine,"Obara, H.;Ikoma, N.;Kazuyuki, S.;Tachi, K.",1995,,,0,0,
2555,"A case of Wilson's disease with fulminan hepatic form survived with plasma exchange, glucagon-insulin (GI) therapy, prostaglandin E<inf>1</inf> (PGE<inf>1</inf>) and haptoglobin. [Japanese]","A 15-year-old girl was admitted to our hospital, because of general malaise and icterus. Based on the data of urinar copper and serum ceruloplasmin as well as Kayser-Fleisher ring in the cornea, this case was diagnosed as Wilson's disease. Although D-pennicillamine was administered, hepatic encephalopathy, ascites and icterus progressed. The maximum level of total bilirubin showed 80.26 mg/dl. We treated this case with repeated plasma exchange, G1 therapy, PGE<inf>1</inf> and haptoglobin, because she presented progressive hepatic failure and hemolytic anemia. By using the combination therapies described above, the clinical course of this case showed remarkable improvement after five months from onset. This report presented a survived case of Wilson's disease with fulminant hepatic form, and pointed out the importance of various kinds of active therapies.",adolescent;article;case report;clinical examination;female;hepatic encephalopathy;human;jaundice;malaise;plasmapheresis;treatment outcome;Wilson disease/dt [Drug Therapy];glucagon/dt [Drug Therapy];haptoglobin/dt [Drug Therapy];insulin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prostaglandin E1/dt [Drug Therapy],"Ishikawa, T.;Ishikawa, N.;Oota, H.;Yoshida, T.;Honma, A.;Kamimura, T.;Ozaki, T.",1995,,,0,0,
2556,Wilson disease in Iceland: A clinical and genetic study,"A survey of Wilson disease in Iceland has revealed two large kindreds with affected individuals. We have carried out studies of haplotypes of dinucleotide repeat polymorphisms (CA repeats) flanking the Wilson disease gene. The same mutation, a 7-bp deletion, is present in both families, and the clinical features are similar. The haplotype data and nature of the mutation support the existence of a founder chromosome carrying the mutation. This Icelandic mutation was not found in patients of Irish or Scottish origins, who could share some of the Icelandic ancestral genes. Although the protein function is predicted to be completely abolished by the deletion, predicting early-onset liver disease, we find that the patients present with later-onset neurological and psychiatric symptoms. We show that alternative splicing of the transcript in the region of the deletion could contribute to later onset, suggesting that alternative isoforms of the protein might have some functional significance.",alternative RNA splicing;article;autosomal recessive disorder/cn [Congenital Disorder];chromosome 13;chronic liver disease;clinical article;clinical feature;controlled study;copper metabolism;female;gene deletion;genetic polymorphism;human;human cell;Iceland;male;neurologic disease;priority journal;Wilson disease/cn [Congenital Disorder];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine;zinc derivative,"Thomas, G. R.;Jensson, O.;Gudmundsson, G.;Thorsteinsson, L.;Cox, D. W.",1995,May,,0,0,
2557,Wilson's disease. Evolutive panorama of diagnosis and treatment in the last forty years. [Japanese],"In 1912, Wilson and Fleischer independently reported autopsied patients with progressive neurological disorder associated with cirrhosis of the liver, and they proposed that the syndrome could be a specific disease of toxic origin. In 1952, Scheinberg demonstrated a deficiency of serum ceruloplasmin in Wilson's disease, and it became possible to diagnose the illness while the patient was still asymptomatic. In 1956, Walshe introduced penicillamine as the most excellent drug for treatment of the disease. These epoch-making discoveries encouraged Japanese physicians to make early diagnosis and to try prevention of the disease. This lecture was to review the changing panorama in the diagnosis, treatment and prognosis of the disease in the period of forty years focusing on the experiences in Japan. Early detection of the patients based on hypoceruloplasminemia made it possible to investigate the onset ages of an elevation of serum GOT or GPT and the appearance of Kayser-Fleischer (KF) rings. So far, the youngest patients who exhibited high GPT level and KF rings were three years and five years old, respectively. It became popular that an unexpected elevation of serum transaminase in apparently healthy children of three years or more prompted to examine the possibility of Wilson's disease, and an increasing number of non-familial patients in late infancy have been detected. Now, the mass-screening for Wilson's disease is in progress. Follow-up studies on the prophylaxis for more than thirty years definitely proved that the appearance of clinical symptoms was prevented with the continued penicillamine therapy. There were patients who developed symptoms such as hemolytic crisis, motor deterioration and, especially, psychotic or affective disorders after discontinuation of the therapy of several years when they reached twenty to thirty years of age. Now, the urgent problem is how to encourage all the grown-up patients to continue the lifelong therapy.",adult;child;conference paper;drug withdrawal;early diagnosis;follow up;human;liver cirrhosis/dt [Drug Therapy];liver cirrhosis/pc [Prevention];mass screening;onset age;prognosis;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/pc [Prevention];aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Arima, M.",1995,,,0,0,
2558,Acneiform papules on the neck,,adult;article;case report;clinical feature;cryotherapy;elastosis/di [Diagnosis];elastosis/dt [Drug Therapy];elastosis/th [Therapy];female;histopathology;human;intralesional drug administration;medical record;papule;physical examination;priority journal;skin biopsy;topical drug administration;Wilson disease/dt [Drug Therapy];liquid nitrogen;penicillamine/dt [Drug Therapy];triamcinolone acetonide/dt [Drug Therapy],"Kuhn, C. A.;Helm, T. N.;Bergfeld, W. F.;Glanz, S.;Steck, W. D.",1995,,http://dx.doi.org/10.1001/archderm.131.3.341,0,0,
2559,Hepatitis in children. [French],"Hepatitis in children may be infectious, metabolic, toxic or immune mediated. Incidence of hepatitis A is regularly decreasing thanks to the marked improvement of sanitary equipments. Anti-HAV vaccination has recently become available and is efficient in nearly 100% of the cases. Hepatitis B is a major public health problem. A quarter to a third of chronic carriers have acquired this infection during infancy or childhood and constitute a vast reservoir of the virus. Hepatitis B is associated with heavy morbidity and mortality (fulminant hepatitis, cirrhosis, hepatocarcinome). Systematic vaccination is recommended. Pediatric chronic carriers may benefit from alpha-interferon therapy. Hepatitis B is usually confined to several risk groups and tends to follow a chronic course. Materno foetal transmission is described. Other known or unknown viruses may cause hepatitis, such as the severe NANBNC sporadic hepatitis of childhood which may be complicated by bone marrow aplasia. Among metabolic causes, alpha-1-antitrypsin deficiency and Wilson's disease are the most common, the latter neccessitating rapid diagnosis and specific treatment. Auto-immune hepatitis differ markedly in children as compared with adults, and some may be exclusively found in children, such as the Coombs positive autoimmune hepatitis of infancy. Toxic hepatitis may be related to drug, environmental or industrial toxins.",adolescent;autoimmune hepatitis/dt [Drug Therapy];child;hepatitis/dt [Drug Therapy];hepatitis/pc [Prevention];hepatitis A/dt [Drug Therapy];hepatitis A/pc [Prevention];hepatitis B/dt [Drug Therapy];hepatitis B/pc [Prevention];hepatitis C/dt [Drug Therapy];hepatitis C/pc [Prevention];human;review;toxic hepatitis/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];azathioprine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];hepatitis A vaccine/dt [Drug Therapy];hepatitis B vaccine/dt [Drug Therapy];hepatitis C vaccine/dt [Drug Therapy];hepatitis vaccine/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Sokal, E. M.;Buts, J. P.",1995,,,0,0,
2560,Hepatic disorders. Features and appropriate management,"The spectrum of liver disease is extremely wide, with many of the underlying disorders having acute and chronic presentations. Most of the underlying pathogenetic mechanisms are accounted for by autoimmune disease, viral infection and toxic insult. The management strategy of any liver disease is a combination of treating the symptoms and complications that arise, as well as drug therapies relevant to the specific underlying diagnosis. Encephalopathy, ascites, spontaneous bacterial peritonitis, variceal bleeding and pruritus are the main complications at which drug therapy is directed, although in some cases it represents only 1 aspect of the overall management. Drug therapy per se is largely ineffective in acute liver failure with the possible exception of acetylcysteine, but many drugs are used in the management of the constituent components of this complex medical emergency. Treatments for specific liver conditions are expanding, especially in the areas of autoimmune and viral disease. The increasing availability and success of liver transplantation has tended to change the emphasis of management, and it is often not appropriate to exhaust the treatment options before referring the patient for transplantation. A comprehensive review of all liver disease is beyond the scope of this article, but hopefully the important principles of management and commonly occurring clinical decisions are discussed.",alcohol liver disease/dt [Drug Therapy];ascites/dt [Drug Therapy];ascites/th [Therapy];autoimmunity;bacterial peritonitis/co [Complication];bacterial peritonitis/dt [Drug Therapy];biliary cirrhosis/dt [Drug Therapy];bleeding/co [Complication];bleeding/dt [Drug Therapy];bleeding/su [Surgery];bleeding/th [Therapy];brain disease/co [Complication];brain disease/dt [Drug Therapy];cardiovascular disease/co [Complication];cardiovascular disease/dt [Drug Therapy];clinical trial;endoscope;essential fatty acid deficiency/co [Complication];hepatitis B/dt [Drug Therapy];hepatitis B/su [Surgery];hepatitis C/dt [Drug Therapy];human;hypercholesterolemia/co [Complication];kidney failure/co [Complication];kidney failure/dt [Drug Therapy];kidney failure/th [Therapy];liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver failure/dt [Drug Therapy];liver transplantation;malabsorption/co [Complication];metabolic disorder/co [Complication];neurologic disease/co [Complication];neurologic disease/dt [Drug Therapy];neurologic disease/th [Therapy];osteoporosis/co [Complication];osteoporosis/dt [Drug Therapy];paracentesis;patient care;primary sclerosing cholangitis/dt [Drug Therapy];pruritus/co [Complication];respiratory tract disease/co [Complication];review;Wilson disease/dt [Drug Therapy];antibiotic agent/dt [Drug Therapy];antiinflammatory agent/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];azathioprine/dt [Drug Therapy];beta adrenergic receptor blocking agent/ct [Clinical Trial];beta adrenergic receptor blocking agent/dt [Drug Therapy];colchicine/dt [Drug Therapy];colestyramine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];disaccharide/dt [Drug Therapy];disaccharide/pd [Pharmacology];diuretic agent/dt [Drug Therapy];dopamine/dt [Drug Therapy];flumazenil/ct [Clinical Trial];flumazenil/dt [Drug Therapy];inotropic agent/dt [Drug Therapy];interferon/dt [Drug Therapy];methotrexate/dt [Drug Therapy];penicillamine/dt [Drug Therapy];propylthiouracil/dt [Drug Therapy];rifampicin/dt [Drug Therapy];steroid/dt [Drug Therapy];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];vasoconstrictor agent/dt [Drug Therapy];zinc/dt [Drug Therapy],"Aldersley, M. A.;O'Grady, J. G.",1995,,,0,0,
2561,Wilson's disease treated with trientine during pregnancy,,adult;article;case report;copper blood level;drug efficacy;female;human;maternal disease;pregnancy;priority journal;treatment outcome;treatment planning;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];trientine/dt [Drug Therapy],"Devesa, R.;Alvarez, A.;De las Heras, G.;De Miguel, J. R.",1995,,,0,0,
2562,Acute liver failure as the initial manifestation of Wilson disease. [German],"BACKGROUND: Establishing an early diagnosis is crucial to successfully treat mostly young patients with sudden onset acute hepatic failure as the initial symptom of Wilson's disease. Recognition of the entity of Wilsonian fulminant hepatitis is important, because liver transplantation improves survival if performed in a timely fashion. METHODS: Retrospective case analysis regarding characteristic profile of standard laboratory parameters and clinical course of acute Wilsonian hepatic failure. RESULTS: In two female patients (age 17 and 27 years) with non-autoimmune hemolysis serum AST and ALT levels were only moderately elevated with a conspicuously diminished ALT activity and relatively low serum alkaline phosphatase (AP) levels. Despite immediate application of D-Penicillamin one patient died from complications of multiorgan failure. CONCLUSION: In fulminant Wilsonian hepatic failure the AP/bilirubin ratio is usually below 2. Additionally calculation of free copper concentration in serum and renal excretion of ionic copper in combination with non-autoimmune hemolysis provide clues to establish an early diagnosis of Wilsonian hepatic failure.",adolescent;adult;article;case report;fatality;female;hepatic encephalopathy/di [Diagnosis];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/et [Etiology];human;liver;liver failure/di [Diagnosis];liver failure/dt [Drug Therapy];liver failure/et [Etiology];liver function test;multiple organ failure/di [Diagnosis];multiple organ failure/dt [Drug Therapy];multiple organ failure/et [Etiology];pathology;retrospective study;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy],"Herrmann, S.;Hofmann, W.;Theilmann, L.",1995,15 Aug,,0,0,
2563,Visceral manifestations of Wilson-Konovalov disease (analysis of 22 cases). [Russian],"Twenty-two patients with Wilson-Konovalov disease (WKD) had not only hepatic but also visceral symptoms: renal affection, cutaneous vasculitis, arthralgias, endocrine disorders, etc. In 8 of these 22 patients extrahepatic symptoms appeared 10 years before hepatic signs. The latter were distinguished by the frequency of edematic-ascitic syndrome, hemolytic episodes, hemorrhagic syndrome; low activity of serum aminotransferase. Initial neurological symptoms were registered in 6 patients only. 12 patients benefited from copper-eliminating therapy. 4 patients had advanced process which caused death. To detect WKD early, special diagnostic tests should be conducted in all subjects under 45 with hepatic symptoms or WKD-specific visceral manifestations. Examination of the patients' sibs is also desirable.",adolescent;adult;article;comparative study;differential diagnosis;female;human;male;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ignatova, T. M.;Il'ina, N. A.;Potapova, A. V.;Iusov, S. P.;Popova, I. V.",1995,,,0,0,
2564,"Disordered copper metabolism in LEC rats, an animal model of Wilson disease: Roles of metallothionein","Disordered copper (Cu) metabolism in LEC rats, an animal model of Wilson disease, was characterized by specifying Cu in the liver, bloodstream and kidneys during the accumulation process and at the onset of jaundice; Cu accumulates in the liver with age in a form bound to metallothionein (MT). Massive Cu is liberated from MT when Cu accumulates beyond the capacity of MT synthesis. Cu bound to MT is not supplied to ceruloplasmin (Cp) during its maturation process, while the metal is transferred to Cu, zinc (Zn)- superoxide dismutase (SOD) directly from MT. Cu ions not bound to MT are transferred to Cp and the holo-Cp is excreted into the bloodstream near and at the onset of jaundice. Cu accumulated in the liver in a form bound to MT is removed selectively by tetrathiomolybdate (TTM), and the animal at the beginning of the onset of jaundice recovers by the chelation therapy. Mechanisms of the removal reaction were proposed to involve formation of MT/TTM, Cu/TTM, and/or polymeric Cu/TTM complexes according to the stoichiometry of TTM to Cu. The Cu/TTM complex was assumed to be effluxed into the bloodstream and to bind specifically to albumin. TTM is taken up by the liver in accordance with the Cu content. The toxicity of Cu was explained by the active oxygen species produced in Cu-mediated reactions, and the participation of MT.",animal experiment;animal model;article;chelation;copper metabolism;gene expression;genetic disorder;genetic predisposition;jaundice;nonhuman;priority journal;rat;Wilson disease;albumin;ceruloplasmin;metallothionein/pd [Pharmacology],"Suzuki, K. T.",1995,,,0,0,
2565,Effect of (D)-penicillamine on oxalate production [9],,adolescent;animal experiment;calcium excretion;calcium oxalate stone/pc [Prevention];calcium urine level;case report;enzyme activity;human;hyperoxaluria/si [Side Effect];letter;male;nonhuman;oral drug administration;patient monitoring;priority journal;rat;urine level;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];alanine glyoxylate aminotransferase;aspartate aminotransferase/ec [Endogenous Compound];oxalic acid/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pyridoxal 5 phosphate/ec [Endogenous Compound];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy],"Baker, P.;Bais, R.;Rofe, A.",1995,,,0,0,
2566,Excretion of copper in copper-overloaded Fischer and Long-Evans cinnamon rats treated with tetrathiomolybdate,"The mode of excretion of Cu from the liver was studied in Long-Evans Cinnamon (LEC) rats with an inherently abnormal Cu metabolism and in Cu-loaded Fischer rats by using tetrathiomolybdate (TTM). LEC rats were fed a semisynthetic diet containing 10 ppm Cu for 40 days. Fischer rats were fed the same diet containing 10 or 500 ppm Cu for 40 days. TTM was injected subcutaneously into the rats at a dose of 5.0 mg/kg at 24-h intervals for the last 3 days. The hepatic Cu concentrations were 392 and 194 mug/g in Fischer and LEC rats not treated with TTM, respectively. However, the hepatic MT concentration was about 10 times higher in the LEC rats than in the Fischer rats. In Fischer rats, the excretion of Cu into the bile and serum was increased by TTM, resulting in a reduction of the hepatic Cu concentration (264 mug/g). In LEC rats, leakage of Cu into the serum, but not biliary excretion of Cu, was accelerated by TTM injection. The increased serum Cu concentration was 0.7 mug/ml in LEC rats compared with 14.4 mug/ml in Fischer rats. The hepatic Cu concentration was 170 mug/g in LEC rats treated with TTM. Serum ceruloplasmin activity (as oxidase) in LEC rats was not increased by the injection of TTM. Our results suggest that TTM can remove Cu from the liver, via blood and, furthermore, that the Cu metabolism in LEC rats is different from that in Cu-fed rats.",Cu-loaded Fischer rats;LEC rats;Wilson's disease;animal experiment;animal model;article;bile;biliary excretion;ceruloplasmin blood level;controlled study;copper blood level;copper metabolism;diet;excretion;female;liver;liver level;metabolic disorder/et [Etiology];nonhuman;priority journal;rat;serum;subcutaneous drug administration;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper;tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pd [Pharmacology],"Sugawara, N.;Yuasa, M.;Sugawara, C.",1995,,,0,0,
2567,Wilson disease. [Dutch],"Two cases of Wilson's disease are reported. A review of the pathogenesis, the clinical aspects, the diagnosis and the therapy of this rare metabolic disorder is given. The disease should be suspected and searched for in all young patients with an unexplained hepatic or neuropsychiatric symptomatology. Investigation of the parameters of copper metabolism can confirm or exclude the diagnosis. Untreated, the disease unvariably runs a fatal course; when timely and adequately treated, however, life expectancy becomes normal.",adult;article;case report;clinical feature;female;human;leukopenia/si [Side Effect];nephrotoxicity/si [Side Effect];oral drug administration;pathogenesis;symptomatology;thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Mast, A.",1995,,,0,0,
2568,Wilson's disease in personal material--disturbances in hemostasis. [Polish],"Genetically determined impairment of copper excretion from the liver into the bile in Wilson's disease (WD) cause that ""free copper"" is accumulated in toxic amounts not only in the liver, but also in other organs. In WD liver biopsy often could not be made because of serious disturbances in hemostasis. The aim of the study was: a) to demonstrate our 9 patients with various form of WD. b) to examine some blood clotting factors and compare the results with these obtained in other liver diseases. The diagnosis of Wilson's disease was made on the basis of disturbed copper metabolism. Among our 9 patients (8 women and 1 man, between 17-33 years old) we diagnosed: 3 patients with fulminant Wilson's disease with all day deep jaundice, hemolytic anemia, haemorrhagic diathesis and liver failure, died, 2 patients with active chronic hepatitis, hemolytic anemia and haemorrhagic diathesis, 2 patients with liver cirrhosis, haemorrhagic diathesis, Kayser-Fleisher ring, neuropsychiatric syndrome, 2 asymptomatic patients without haemorrhagic diathesis. The prothrombin index and the factors of prothrombin stem (II, V, VII, X) were lower than in other kinds of cirrhosis. After treatment with d-penicillamine the clothing factors returned near to the norm, similar as the biochemical and immunological results.",adolescent;adult;article;blood clotting disorder/et [Etiology];clinical trial;comparative study;controlled clinical trial;controlled study;female;human;liver disease/co [Complication];male;middle aged;pathophysiology;Wilson disease/co [Complication];Wilson disease/di [Diagnosis],"Jablonska-Kaszewska, I.;Dabrowska, E.;Ozieblowski, A.",1995,Sep,,0,0,
2569,Wilson disease: a new case treated with trientine. [Spanish],"Hepatolenticular degeneration, also known as Wilson's disease (WD), is an infrequent hereditary disorder which is transmitted in recessive autosomic fashion: its genetic defect is to be found in the long branch of chromosome 13 (13q14.3) and allows disorder to take place which has not been sufficiently clarified, in the bilious excretion of the copper (Cu) which is deposited in an anomalous manner on a level with different organic tissues, giving rise to characteristic clinical manifestations which are, basically, of a neurological, hepatic, psychiatric and ocular nature. We present the case of a young patient whose case began, four years ago, with depressive-type manifestations, with diagnosis only being made now. Our opinion on the early detection of asymptomatic patients is commented on, along with that concerning the effectiveness and safety of therapeutic alternatives to D-penicilamine.",adult;article;blood;brain cortex;brain ventricle;case report;chromosome 13;computer assisted tomography;congenital malformation;female;human;nuclear magnetic resonance imaging;pathophysiology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;trientine/ad [Drug Administration];trientine/dt [Drug Therapy],"Moreno Perez-Crespo, J. L.;Garcia de la Rocha, M. L.;Martin Araguz, A.;Olmedilla, N.;Rodriguez Arias, C. A.;Porta, J.;Moreno Martinez, J. M.",1995,1995,,0,0,
2570,Low serum alkaline phosphatase activity associated with severe Wilson's disease. Is the breakdown of alkaline phosphatase molecules caused by reactive oxygen species?,,Alkaline phosphatase activity;Fragmentation;Molecular sizes;Protein quantitation;Reactive oxygen species;Wilson's disease;article;case report;child;controlled study;enzyme activity;female;human;human tissue;male;normal human;priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];acetylsalicylic acid/cb [Drug Combination];acetylsalicylic acid/dt [Drug Therapy];alkaline phosphatase/ec [Endogenous Compound];gabexate/cb [Drug Combination];gabexate/dt [Drug Therapy];glutathione/cb [Drug Combination];glutathione/dt [Drug Therapy];indometacin/cb [Drug Combination];indometacin/dt [Drug Therapy];nafamstat/cb [Drug Combination];nafamstat/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];tocopherol/cb [Drug Combination];tocopherol/dt [Drug Therapy],"Hoshino, T.;Kumasaka, K.;Kawano, K.;Yamagishi, F.;Koyama, I.;Fujimori-Arai, Y.;Nakajima, T.;Komoda, T.",1995,,http://dx.doi.org/10.1016/0009-8981%2895%2906073-M,0,0,
2571,Effects of some chelating agents on urinary copper excretion by the rat,"In order to estimate the potential advantages of new chelating agents which can enhance copper excretion in the chronic copper intoxication arising in Wilson's disease, the relative ability of nine chelating agents to induce the urinary excretion of copper was compared with that of D-penicillamine (DPA) and triethylenetetramine.2HCl (TRIEN), all given ip at 1 mmol/kg to male Sprague-Dawley rats. The compounds examined were as follows: tris(2- aminoethyl)amine.3HCl (TREN), tetraethylenepentamine.5HCl (TETREN), pentaethylenehexamine.6HCl (PENTEN), 1,4,7,11-tetraazaundecane.4HCl (TAUD), 1,5,8,12-tetraazadodecane.4HCl (TADD), 1-N-benzyltriethylenetetramine.HCl (BzTT), 4,7,10,13-tetraazatridecanoic acid.2H<inf>2</inf>SO<inf>4</inf> (TTPA), 1,10-bis(2- pyridylmethyl)-1,4,7,10-tetraazadecane.4HCl (BPTETA), and N,N-bis(2-pyridyl- methyl)-4-(aminomethyl)benzoic acid (4ABA). Of these, BzTT, TTPA, and 4ABA are new chelating agents not previously reported. The factors by which these chelating agents enhanced copper excretion over control (untreated) levels were as follows: DPA, 7.2; TREN, 1.6; TRIEN, 4.0; TETREN, 10.1; PENTEN, 7.8; TAUD, 7.8; TADD, 2.6; TTPA, 5.6; BzTT, 1.8; and 4ABA, 5.5. The results indicate that it may well be possible to develop additional chelating agents which are equal or superior to those now used in the treatment of Wilson's disease, as well as structural types whose immunological properties may be significantly different from DPA or TRIEN, the compounds currently used in the clinic for this disorder.","animal experiment;article;controlled study;copper metabolism;drug effect;male;nonhuman;rat;urinary excretion;Wilson disease/dt [Drug Therapy];1 benzyltriethylenetetramine/cm [Drug Comparison];1 benzyltriethylenetetramine/dv [Drug Development];1 benzyltriethylenetetramine/dt [Drug Therapy];1,10 bis(2 pyridylmethyl) 1,4,7,10 tetraazadecane/cm [Drug Comparison];1,10 bis(2 pyridylmethyl) 1,4,7,10 tetraazadecane/dv [Drug Development];1,10 bis(2 pyridylmethyl) 1,4,7,10 tetraazadecane/dt [Drug Therapy];1,4,7,11 tetraazaundecane/cm [Drug Comparison];1,4,7,11 tetraazaundecane/dv [Drug Development];1,4,7,11 tetraazaundecane/dt [Drug Therapy];1,5,8,12 tetraazadodecane/cm [Drug Comparison];1,5,8,12 tetraazadodecane/dv [Drug Development];1,5,8,12 tetraazadodecane/dt [Drug Therapy];4 [n,n bis(2 pyridylmethyl)aminomethyl]benzoic acid/cb [Drug Combination];4 [n,n bis(2 pyridylmethyl)aminomethyl]benzoic acid/dv [Drug Development];4 [n,n bis(2 pyridylmethyl)aminomethyl]benzoic acid/dt [Drug Therapy];4,7,10,13 tetraazatridecanoic acid/cm [Drug Comparison];4,7,10,13 tetraazatridecanoic acid/dv [Drug Development];4,7,10,13 tetraazatridecanoic acid/dt [Drug Therapy];chelating agent/cm [Drug Comparison];chelating agent/dv [Drug Development];chelating agent/dt [Drug Therapy];copper;penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];pentaethylenehexamine/cm [Drug Comparison];pentaethylenehexamine/dv [Drug Development];pentaethylenehexamine/dt [Drug Therapy];tetraethylenepentamine/cm [Drug Comparison];tetraethylenepentamine/dv [Drug Development];tetraethylenepentamine/dt [Drug Therapy];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];tris(2 aminoethyl)amine/cm [Drug Comparison];tris(2 aminoethyl)amine/dv [Drug Development];tris(2 aminoethyl)amine/dt [Drug Therapy];unclassified drug","Jones, M. M.;Singh, P. K.;Zimmerman, L. J.;Gomez, M.;Albina, M. L.;Domingo, J. L.",1995,,http://dx.doi.org/10.1021/tx00049a007,0,0,
2572,Formation of copper-metallothionein/tetrathiomolybdate complex is the first step in removal of Cu from LEC rats,"Copper (Cu) accumulating in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color) is bound to metallothionein (MT). Mechanisms for the removal of Cu by tetrathiomolybdate (TTM) were studied by the high performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) method. MT containing Cu and cadmium (Cd) (Cu,Cd- MT) was reacted with TTM at a molar ratio of TTM/Cu = 0.5. A complex containing Cu, Cd and molybdenum (Mo) was formed and migrated to a position corresponding to an MT dimer on a gel filtration column. This complex designated previously as a dimer of MT through -S-Cu-S- bridge was revised to be a complex formed between MT and TTM through (MT)-S-Cu-S-(TTM) bridge with differing numbers of TTM bound to MT.",animal experiment;animal model;article;chelation therapy;chromosome 13;complex formation;controlled study;copper metabolism;DNA drug complex;drug accumulation;drug binding;drug withdrawal;high performance liquid chromatography;liver injury;nonhuman;priority journal;rat;reaction analysis;Wilson disease;copper/an [Drug Analysis];copper/cb [Drug Combination];copper/it [Drug Interaction];metallothionein/an [Drug Analysis];metallothionein/cb [Drug Combination];metallothionein/it [Drug Interaction];tetrathiomolybdic acid/an [Drug Analysis];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/it [Drug Interaction],"Suzuki, K. T.;Ogra, Y.",1995,,,0,0,
2573,Case report: Concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilsons's disease,"Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.",adult;article;brain injury;brain stem;case report;concussion;human;maladjustment;male;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Marcus, A.;Ammermann, C.;Klein, M.;Schmidt, M. H.",1995,,http://dx.doi.org/10.1007/BF01987966,0,0,
2574,Removal and efflux of copper from Cu-metallothionein as Cu/tetrathiomolybdate complex in LEC rats,"Tetrathiomolybdate (TTM) removes copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color). The first step in the removal of Cu from Cu-MT has been shown to form a complex between MT and TTM through (MT)-S-Cu-S-(TTM) bridges (referred to as MT/TTM complex). Additional TTM was demonstrated to remove Cu from MT/TTM complex as the second step to form Cu/TTM complex by liberating MT. The Cu/TTM complex binds specifically to albumin in serum and to high molecular weight proteins in the absence of albumin, and is assumed to be a form of Cu for efflux by the treatment with TTM.",animal cell;article;chemical reaction kinetics;complex formation;copper metabolism;drug distribution;drug effect;liver injury;nonhuman;priority journal;protein binding;rat;reaction analysis;transport kinetics;Wilson disease;copper/an [Drug Analysis];copper/cb [Drug Combination];metallothionein/an [Drug Analysis];metallothionein/cb [Drug Combination];tetrathiomolybdic acid/an [Drug Analysis];tetrathiomolybdic acid/cb [Drug Combination],"Ogra, Y.;Suzuki, K. T.",1995,,,0,0,
2575,"Transfer of copper and zinc from ionic and metallothionein - Bound forms to Cu, Zn - superoxide dismutase","Reactivity in transfer of copper (Cu) and zinc (Zn) to their binding sites of superoxide dismutase (SOD) was examined in vitro by the HPLC/atomic absorption spectrophotometry. Ionic Cu (cuprous and cupric ions) were incorporated more efficiently than the metal bound to metallothionein. Cu binds not only to the Cu-binding site but also to the Zn-binding site. Although Zn in the reaction medium and the metal bound to the Zn-binding site of SOD affected little the reactivity in binding of ionic Cu, they disturbed the reactivity of Cu bound to metallothionein to the Cu-binding site. Both ionic and metallothionein-bound Zn were transferred at a comparable efficiency to the Zn-binding site but not to the Cu-binding site. Co-existing ionic Cu but not metallothionein-bound Cu in the medium inhibited the binding of Zn to SOD. The results indicate that ionic Cu can be transferred to both Cu- and Zn-binding sites of SOD more efficiently than metallothionein-bound Cu, while both ionic and metallothionein-bound Zn are transferred only to Zn- binding site at a comparable efficiency.",animal tissue;article;binding affinity;binding site;copper metabolism;enzyme activity;enzyme binding;ion transport;liver metabolism;nonhuman;pathophysiology;priority journal;rat;Wilson disease/et [Etiology];copper ion;copper zinc superoxide dismutase/ec [Endogenous Compound];metallothionein,"Suzuki, K. T.;Kuroda, T.",1995,,,0,0,
2576,Late diagnosis of Wilson's disease in a case without onset of symptoms,"Wilson's disease (WD) was diagnosed on the basis of a liver biopsy, blood investigations and a radio copper test in a 60-year-old, neurologically normal female with uncharacteristic gastrointestinal complaints. Since this patient never developed symptoms indicative for WD this case suggests the possibility of a subclinical course of untreated WD.",adult;article;case report;female;human;nuclear magnetic resonance;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine,"Hefter, H.;Weiss, P.;Wesch, H.;Stremmel, W.;Feist, D.;Freund, H. J.",1995,,,0,0,
2577,Wilson's disease revealed by magnetic resonance imaging. [Dutch],"In a 21-year-old woman with a smaller and sloppy handwriting, drooling especially when stooping, sporadic choking, clumsiness, and frequent stumbling, Wilson's disease was diagnosed. The medical history disclosed a short period of haemolytic anaemia with transient hepatic failure, and irregular menstruation periods with infertility. On examination there were no signs of liver or spleen enlargement. She was slow, had an expression-less face and mild dysarthria, and slight impairment of the coordination of the limbs. Magnetic resonance imaging of the brain showed bilateral hyperintensive lesions of the basal ganglia on T<inf>2</inf>W images. Zinc therapy induced a good biochemical response and there was also some clinical improvement. Linkage analysis within the family identified one other asymptomatic homozygotically affected sister. A diagnostic delay occurs frequently due to relative unfamiliarity with this rare disease and due to its variable clinical expression.",adult;article;case report;clinical feature;family study;female;genetic linkage;human;nuclear magnetic resonance imaging;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];zinc/dt [Drug Therapy],"Van Den Berg, J. S. P.;Hoogenraad, T. U.;Duyn, J. A.;Verbeeten Jr, B.;Aalfs, C. M.;De Visser, M.",1995,,,0,0,
2578,Conceptual advances in the pathogenesis and treatment of childhood metabolic liver disease,,alpha 1 antitrypsin deficiency/di [Diagnosis];alpha 1 antitrypsin deficiency/et [Etiology];alpha 1 antitrypsin deficiency/su [Surgery];alpha 1 antitrypsin deficiency/th [Therapy];childhood disease;clinical trial;diet restriction;emphysema;enzyme replacement;Gaucher disease/di [Diagnosis];Gaucher disease/dt [Drug Therapy];gene therapy;human;intravenous drug administration;liver disease;liver transplantation;nonhuman;oral drug administration;priority journal;review;splenectomy;splenomegaly/su [Surgery];tyrosinemia/di [Diagnosis];tyrosinemia/dt [Drug Therapy];tyrosinemia/et [Etiology];tyrosinemia/su [Surgery];tyrosinemia/th [Therapy];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];alglucerase/dt [Drug Therapy];alpha 1 antitrypsin/ec [Endogenous Compound];cyclohexane derivative/dt [Drug Therapy];nitisinone/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenylalanine;tyrosine;unclassified drug;zinc/dt [Drug Therapy],"Teckman, J.;Perlmutter, D. H.",1995,,http://dx.doi.org/10.1016/0016-5085%2895%2990229-5,0,0,
2579,Copper metabolism leading to and following acute hepatitis in LEC rats,"The accumulation process of copper (Cu) in the liver and the following metabolic disorder of Cu were examined in LEC rats, a mutant strain which accumulates Cu with age and shows spontaneous acute hepatitis and/or hepatoma. Cu concentration in the liver of female rats was ~220 mug/g liver at 2 weeks of age, decreased to 100 mug/g liver at 4-6 weeks, and then started to increase with age linearly to the highest concentration of 250 mug/g liver at 16 weeks. Although the Cu level expressed by concentration (mug/g liver) decreased during weaning, it increased linearly with age when it was expressed by content (mg/liver), indicating a constant and preferential accumulation of Cu in the liver. Cu concentration stopped increasing at 16 weeks in the liver, followed by a sudden decrease to 1/2 the highest level. Biological markers (serum lactate dehydrogenase and glutamic-oxaloacetic transaminase activities) for liver damage started to increase, together with the appearance of signs of jaundice, when Cu attained the highest concentration. Distributions of Cu and zinc (Zn) in the supernatant fraction of the liver indicated that both metals were mostly distributed to metallothionein (MT) and, to a small extent, to superoxide dismutase on a gel filtration column throughout the course of the experiments. Serum Cu concentration started to increase in a form of ceruloplasmin, together with serum marker enzyme activities for liver damage. Cu concentration in the kidneys also started to increase after the increase of serum Cu. The results indicate that Cu accumulates in the form of MT in the liver of LEC rats to a maximum level of ~ 250 mug/g liver, and then decreases suddenly with the onset of acute hepatitis. The maximum level seems to be related to the capacity of MT synthesis, and acute hepatitis is assumed to occur when Cu accumulates beyond the capacity. Serum Cu started to increase, from the abnormally low level, when the metal accumulated beyond the capacity of MT synthesis in the liver, and it was partly reabsorbed by the kidneys and the rest was excreted into urine. Changes in iron and zinc levels were determined and discussed in relation to those of Cu.",Copper;Copper toxicity;Hepatitis;hplc-icp;Iron;LEC rat;Metallothionein;Wilson disease;acute hepatitis;animal experiment;animal tissue;article;bioaccumulation;controlled study;copper metabolism;female;jaundice;kidney;liver toxicity;nonhuman;priority journal;protein synthesis;rat;aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/to [Drug Toxicity];iron/ec [Endogenous Compound];lactate dehydrogenase/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];zinc,"Suzuki, K. T.;Kanno, S.;Misawa, S.;Aoki, Y.",1995,,http://dx.doi.org/10.1016/0300-483X%2894%2902927-M,0,0,
2580,Hepatology. [French],"This paper summarizes new therapeutic advances in hepatology during 1994 and updates the treatments already known. For this purpose, we have examined all randomized prospective studies made on human beings, published at that time. Though 1994 mostly provided corroboration of data already known, there were a few new advances such as the diagnosis of hepatitis E, thanks to the commercialization of a serological diagnosis test.",alcohol liver disease/dt [Drug Therapy];biliary cirrhosis/dt [Drug Therapy];cholangitis/dt [Drug Therapy];drug research;endoscopy;hepatitis/dt [Drug Therapy];hepatitis/pc [Prevention];hepatitis/su [Surgery];human;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver transplantation;medical research;review;Wilson disease/dt [Drug Therapy];acetylcysteine/dt [Drug Therapy];albendazole/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];antiinfective agent/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];azathioprine/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];colestyramine/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];flumazenil/dt [Drug Therapy];hepatitis vaccine/dt [Drug Therapy];lactitol/dt [Drug Therapy];lactulose/dt [Drug Therapy];mebendazole/dt [Drug Therapy];metoclopramide/dt [Drug Therapy];octanoin/dt [Drug Therapy];ondansetron/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];prednisone/dt [Drug Therapy];somatostatin/dt [Drug Therapy];tacrolimus/dt [Drug Therapy];terlipressin/dt [Drug Therapy];trientine/dt [Drug Therapy];unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];vasopressin/dt [Drug Therapy],"Margalith, D.;Fasel, J.;Lavanchy, D.;Gonvers, J. J.;Gillet, M.",1995,,,0,0,
2581,Life-long drug therapy required for Wilson's disease,,abdominal cramp/si [Side Effect];allergic reaction/si [Side Effect];anemia/si [Side Effect];article;copper metabolism;diet;drug mechanism;fever/si [Side Effect];genetic disorder;human;lifespan;nausea/si [Side Effect];proteinuria/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];copper/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];iron/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];pyridoxine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc/ae [Adverse Drug Reaction];zinc/cm [Drug Comparison];zinc/do [Drug Dose];zinc/dt [Drug Therapy];zinc/pd [Pharmacology],Anonymous,1995,,,0,0,
2582,Potential complication of multivitamin use in patients with Wilson's disease [3],,diet;human;letter;oral drug administration;Wilson disease/dt [Drug Therapy];copper;multivitamin;penicillamine/dt [Drug Therapy];zinc/ad [Drug Administration];zinc/dt [Drug Therapy],"Campellone, J. V.",1995,,,0,0,
2583,"Zinc-induced deterioration in Wilson's disease aborted by treatment with penicillamine, dimercaprol, and a novel zero copper diet [2]",,adult;case report;clinical feature;diet restriction;dysarthria;dyskinesia;female;flexion contracture;human;letter;priority journal;torticollis;tremor;vomiting;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];copper;dimercaprol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pergolide/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Walshe, J. M.;Munro, N. A. R.",1995,,,0,0,
2584,"Copper: Not too little, not too much, but just right","Copper is an essential trace element with a well established mechanism for maintaining balance of the metal in the body, which is controlled by at least two genes. Disruption of one gene on the X chromosome determines a defect in the process of copper absorption, with consequent deficiency of available copper at the cellular level. This results in abnormalities of collagen formation and brain maturation, leading to early death. As yet there is no effective treatment. Disruption of the other copper controlling gene, located on chromosome 13, is associated with accumulation of excess copper in-the body, first in the liver leading to cirrhosis, and then in the brain giving rise to destruction of the centre of motor control and, frequently, changes in personality. Copper excess can also cause renal damage, osteoarticular changes and joint pains. If the renal lesion leads to calcium loss in the urine and other tubular defects, there may be osteoporosis or, occasionally, osteomalacia with pathological fractures. In this disease, the abnormal stores of copper can be mobilised with chelating agents or depleted by the administration of zinc salts or thiomolybdate. This usually, but not invariably, leads to improvement or even complete reversal of symptoms. Brain lesions, as demonstrated by computed tomography or magnetic resonance imaging, may also resolve. The mechanism of this phenomenon is obscure but suggests that the long held doctrine that there is no recovery in the central nervous system may have to be reviewed.",absorption;arthralgia/et [Etiology];brain injury/et [Etiology];brain maturation;calcium excretion;chromosome 13;collagen synthesis;computer assisted tomography;copper metabolism;death;gene mutation;genetic regulation;human;kidney injury/et [Etiology];liver cirrhosis/et [Etiology];liver transplantation;Menkes syndrome/et [Etiology];motor control;nuclear magnetic resonance imaging;osteomalacia/et [Etiology];osteoporosis/et [Etiology];pathologic fracture/et [Etiology];personality disorder/et [Etiology];review;side effect;subcutaneous drug administration;urinary excretion;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];X chromosome;calcium/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];chelating agent/pd [Pharmacology];copper/ec [Endogenous Compound];copper/pd [Pharmacology];copper derivative/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];thiomolybdic acid/pd [Pharmacology];trace element/ec [Endogenous Compound];trace element/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy];zinc derivative/dt [Drug Therapy];zinc derivative/pd [Pharmacology],"Walshe, J. M.",1995,,,0,0,
2585,Clinical and magnetic resonance imaging findings in a case of Wilson disease,,adult;article;basal ganglion;brain tomography;case report;ceruloplasmin blood level;clinical feature;computer assisted tomography;copper blood level;human;male;neurologic examination;nuclear magnetic resonance imaging;priority journal;tremor/co [Complication];tremor/dt [Drug Therapy];Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];anticonvulsive agent/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];clonazepam/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Ozer, F.;Karsidag, S.;Akbari, H.;Arpaci, B.",1995,,,0,0,
2586,Wilson's disease: a review apropos of a clinical experience in 16 patients. [Spanish],"Wilson's Disease is an inherited disorder of copper metabolism. We report 16 patients (6 males) with the disease; 6 had hepatic involvement exclusively, 4 had neurological involvement, 3 had a neurological and hepatic involvement and 3 were asymptomatic. The age onset was 9 years for hepatic and 17 years for neurologic involvement. The mean delay in diagnosis was 14 months. Chronic hepatitis, cirrhosis and fulminant hepatic failure were the clinical forms of liver disease. Patients with neurologic disorders had behavioral disturbances and extrapyramidal manifestations such as dystonia and parkinsonism. Patients had a good response to penicillamine, except 3 that died of liver complications, in whom the treatment was delayed or discontinued. We conclude that this metabolic disease must be suspected in pubertal children and in adults of less than 30 years old with liver disease of unknown origin or behavioral alterations associated to an extrapyramidal syndrome.",adolescent;adult;article;blood;central nervous system disease/di [Diagnosis];child;clinical trial;computer assisted tomography;female;genetics;human;liver;liver disease/di [Diagnosis];male;multicenter study;pathology;pregnancy;preschool child;retrospective study;urine;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/an [Drug Analysis];copper;penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Miranda, M.;Brinck, P.;Roessler, J. L.;Troncoso Sch, M.;Gonzalez, M.;Alarcon, T.;Villagra, R.",1995,Sep,,0,0,
2587,MR of the liver in Wilson's disease. [German],"To show that Wilson's disease is one likely cause of multiple low-intensity nodules of the liver we obtained MR images in 16 patients with clinically and histopathologically confirmed Wilson's disease. Corresponding to morphological changes MRI enabled the subdivision of the patients into two groups. Using a T<inf>2</inf>-weighted spin-echo sequence (TR/TE = 2000/45-90) liver parenchyma showed multiple tiny low-intensity-nodules surrounded by high-intensity septa in 10 out of 16 patients. 5 patients had also low-intensity nodules in T<inf>1</inf>-weighted images (TR/TE = 600/20). In patients of this group histopathology revealed liver cirrhosis (n = 7) and fibrosis (n = 2). Common feature of this patient group was marked inflammatory cell infiltration into fibrous septa, increase of copper concentration in liver parenchyma and distinct pathological changes of laboratory data. In the remaining 6 patients no pathological change of liver morphology was demonstrated by MRI corresponding to slight histopathological changes of parenchyma and normal laboratory data. As low-intensity nodules surrounded by high intensity septa can be demonstrated in patients with marked inflammatory infiltration of liver parenchyma MRI may help to define Wilson patients with poorer prognosis. In patients with low-intensity nodules of the liver and unknown cause of liver cirrhosis laboratory data and histopathology should be checked when searching for disorders of copper metabolism.",liver cirrhosis;mrt;regenerating nodules;Wilson's disease;adolescent;adult;article;clinical article;diagnosis;female;human;intravenous drug administration;liver cirrhosis/di [Diagnosis];liver regeneration;male;nuclear magnetic resonance imaging;priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];gadolinium pentetate;penicillamine/dt [Drug Therapy],"Vogl, T. J.;Steiner, S.;Hammerstingl, R.;Schwarz, S.;Kraft, E.;Weinzierl, M.;Felix, R.",1994,,,0,0,
2588,Cerebral magnetic resonance in Wilson's disease. [Italian],"The authors describe the typical and atypical MR findings of brain abnormalities in Wilson's disease in three patients affected with severe neurologic disturbances; a low-field MR unit was used. Radiologic findings included atrophic changes and focal lesions. Two patients had basal ganglia, brain stem and dentate alterations; lesions in the corpus callosum (a site not yet described in Wilson's disease) were seen. The third case had putaminal lesions which improved after penicillamine therapy. Cerebral abnormalities were demonstrated as areas of increased signal on T2-weighted images; T1 and T2 shortening due to magnetic susceptibility phenomena was not seen. Two major MR features were observed: high hyperintensity and peripheral location of putaminal lesions and sparing of the medial thalami in diffuse basal ganglia involvement.",adolescent;adult;article;basal ganglion;brain;brain stem;case report;cerebellum nucleus;comparative study;female;human;male;nuclear magnetic resonance imaging;pathology;putamen;thalamus nucleus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Amato, C.;Bisceglie, P.;Moschini, M.",1994,Dec,,0,0,
2589,"Removal of copper from the liver of Long-Evans Cinnamon (LEC) rats by tetrathiomolybdate (TTM) injection: The main excretion route is via blood, not bile","Tetrathiomolybdate (TTM) was injected at a dose of 10 mg/kq bw daily for eight consecutive days into Long-Evans Cinnamon (LEC) rats, which inherently abnormally deposit Cu (260 mug/g) in the liver. The hepatic Cu (100 mug/g) and metallothionein (MT) bound Cu (from 2,600 to 540 mug/g protein) concentrations were decreased greatly by the injection. On the other hand, the renal Cu concentration increased significantly, but the brain Cu concentration only very slightly. The reduction of the hepatic Cu concentration was accompanied by reductions of Zn and Fe concentrations in the liver, kidney and brain. The TTM compound slightly stimulated excretion (about 3-fold) of Cu into the bile, but greatly (about 40-fold) into the blood. In rats not treated with TTM, most biliary (100%) and serum (78%) Cu was recovered in the trichloroacetic acid (TCA) soluble fraction. On the other hand, in rats treated with TTM, bile and serum Cu were recovered overwhelmingly in the TCA insoluble fraction, probably in the form of a Cu- TTM-albumin complex. Our results suggest that although there is an inherent failure in the intrinsic secretory process of Cu from the liver in LEC rats, the TTM compound can remove Cu from Cu-MT, resulting in a decrease of hepatic Cu.",animal experiment;animal model;animal tissue;article;biliary excretion;copper blood level;copper metabolism;drug effect;drug screening;nonhuman;priority journal;rat;tissue distribution;Wilson disease;copper/ec [Endogenous Compound];tetrathiomolybdic acid/dv [Drug Development];tetrathiomolybdic acid/pd [Pharmacology],"Sugawara, N.;Li, D.;Sugawara, C.",1994,,,0,0,
2590,Diseases of the basal ganglia. [German],"Developments in research, diagnosis and therapy of selected basal ganglia diseases are reviewed: The genes for Huntington chorea, for rare forms of dystonia and for Wilson's disease have been identified. The treatment of focal dystonia with botulinum toxin A has been approved now in Germany. In Parkinson's disease the substantia nigra expresses changes in parameters of the redox system and in complex I activity at a very early state of the disease. New therapeutical pharmacological and surgical procedures are summarized. Neuroleptica induced abnormal involuntary movements and the use of atypical neuroleptics in the therapy of dopamimetica induced psychosis in Parkinson's disease are discussed.",basal ganglion;dystonia/dt [Drug Therapy];dystonia/si [Side Effect];dystonia/th [Therapy];human;Huntington chorea/th [Therapy];intramuscular drug administration;neurosurgery;Parkinson disease/si [Side Effect];Parkinson disease/th [Therapy];review;short survey;Wilson disease/th [Therapy];benserazide/cb [Drug Combination];benserazide/dt [Drug Therapy];benserazide plus levodopa/dt [Drug Therapy];botulinum toxin A/dt [Drug Therapy];bromocriptine/cb [Drug Combination];bromocriptine/dt [Drug Therapy];carbidopa/cb [Drug Combination];carbidopa/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];catechol methyltransferase inhibitor/dt [Drug Therapy];clozapine/dt [Drug Therapy];haloperidol/ae [Adverse Drug Reaction];haloperidol/dt [Drug Therapy];leuprorelin/dt [Drug Therapy];levodopa/cb [Drug Combination];levodopa/dt [Drug Therapy];lisuride/cb [Drug Combination];lisuride/dt [Drug Therapy];monoamine oxidase inhibitor/cb [Drug Combination];monoamine oxidase inhibitor/dt [Drug Therapy];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pergolide/cb [Drug Combination];pergolide/dt [Drug Therapy];pramipexole/dt [Drug Therapy];ropinirole/dt [Drug Therapy];selegiline/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy],"Oertel, W.",1994,,,0,0,
2591,Pregnancy and movement disorders,"The concurrence of pregnancy and movement disorders is an uncommon event in a general neurologic practice. Even at specialized movement disorder referral centers, there is insufficient experience to adequately guide management of pregnancy, except perhaps in the case of WD. The questions posed most urgently by patients regard the safety of medication, an issue on which there is insufficient data, and their ability to care for a child for at least the next decade, an issue that differs by disease and social situation. The author's formulation of efficacy and toxicity suggests that certain medications commonly used in movement disorders should be discontinued before pregnancy, if possible. These medications include neuroleptics, amantadine, diazepam, primidone, selegiline, and reserpine. Pregnancy may unmask a pre-existing potential for chorea (i.e., chorea gravidarum) and frequently has a mild exacerbating effect on symptoms of PD; however, it has little effect on other movement disorders. Severe generalized dystonia would probably interfere with vaginal delivery, but the scant existing data suggest minimal effect of movement disorders on pregnancy, childbirth, and neonatal health.",childbirth;chorea/co [Complication];chorea/di [Diagnosis];diagnostic approach route;differential diagnosis;disease course;dystonia/co [Complication];dystonia/di [Diagnosis];dystonia/et [Etiology];human;motor dysfunction/co [Complication];Parkinson disease/co [Complication];Parkinson disease/dt [Drug Therapy];pregnancy complication/co [Complication];priority journal;restless legs syndrome/co [Complication];review;tic/co [Complication];tic/di [Diagnosis];Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];baclofen/dt [Drug Therapy];benzatropine mesilate/dt [Drug Therapy];botulinum toxin A/dt [Drug Therapy];carbidopa plus levodopa/dt [Drug Therapy];clonazepam/dt [Drug Therapy];diazepam/dt [Drug Therapy];diphenhydramine/dt [Drug Therapy];haloperidol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrabenazine/dt [Drug Therapy];trientine;trihexyphenidyl,"Golbe, L. I.",1994,,,0,0,
2592,Allergic stomatitis,"There are basically two types of hypersensitivity reactions involved in allergic stomatitis, type I immediate hypersensitivity, and type IV delayed hypersensitivity. The allergic stomatitides may present with clinical appearances that mimic classic oral vesiculobullous and ulcerative lesions. Differential diagnosis from specific mucosal diseases is important in the treatment of oral allergy. Precise history taking and the elimination of the causative agents will be necessary. The mechanisms involved in oral reactions, etiologic factors, clinical manifestations, and treatment of allergic stomatitis will be described and discussed in this article.",allergic disease/di [Diagnosis];allergic disease/dt [Drug Therapy];allergic disease/et [Etiology];allergic disease/pc [Prevention];allergic disease/si [Side Effect];angioneurotic edema/di [Diagnosis];angioneurotic edema/dt [Drug Therapy];angioneurotic edema/et [Etiology];angioneurotic edema/si [Side Effect];angioneurotic edema/th [Therapy];Crohn disease/di [Diagnosis];delayed hypersensitivity/et [Etiology];dental surgery;differential diagnosis;drug induced disease/di [Diagnosis];drug induced disease/et [Etiology];drug induced disease/si [Side Effect];erythema multiforme/di [Diagnosis];erythema multiforme/dt [Drug Therapy];erythema multiforme/et [Etiology];erythema multiforme/si [Side Effect];food intake;granulomatosis/di [Diagnosis];granulomatosis/dt [Drug Therapy];granulomatosis/et [Etiology];human;hypertension/dt [Drug Therapy];immediate type hypersensitivity/et [Etiology];intravenous drug administration;lichenoid eruption/di [Diagnosis];lichenoid eruption/et [Etiology];lichenoid eruption/si [Side Effect];major clinical study;pathogenesis;pemphigus/di [Diagnosis];pemphigus/et [Etiology];pemphigus/si [Side Effect];review;sarcoidosis/di [Diagnosis];sepsis/dt [Drug Therapy];stomatitis/di [Diagnosis];stomatitis/dt [Drug Therapy];stomatitis/et [Etiology];stomatitis/pc [Prevention];stomatitis/si [Side Effect];subcutaneous drug administration;Wilson disease/dt [Drug Therapy];acetylsalicylic acid/ae [Adverse Drug Reaction];aluminum chloride/to [Drug Toxicity];aminosalicylic acid/ae [Adverse Drug Reaction];antihistaminic agent/dt [Drug Therapy];benzoic acid/to [Drug Toxicity];bismuth/ae [Adverse Drug Reaction];carbamazepine/ae [Adverse Drug Reaction];chloroquine/ae [Adverse Drug Reaction];corticosteroid/ad [Drug Administration];corticosteroid/dt [Drug Therapy];cyanamide/ae [Adverse Drug Reaction];dapsone/ae [Adverse Drug Reaction];dipeptidyl carboxypeptidase inhibitor/ae [Adverse Drug Reaction];dipeptidyl carboxypeptidase inhibitor/dt [Drug Therapy];fenclofenac/ae [Adverse Drug Reaction];gold derivative/ae [Adverse Drug Reaction];kaolin pectin/cb [Drug Combination];local anesthetic agent/ae [Adverse Drug Reaction];local anesthetic agent/ad [Drug Administration];local anesthetic agent/cb [Drug Combination];mepacrine/ae [Adverse Drug Reaction];meprobamate/ae [Adverse Drug Reaction];mercury/to [Drug Toxicity];methacrylic acid methyl ester/to [Drug Toxicity];methyldopa/ae [Adverse Drug Reaction];nickel/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillin derivative/ae [Adverse Drug Reaction];penicillin derivative/dt [Drug Therapy];streptomycin/ae [Adverse Drug Reaction];terfenadine/dt [Drug Therapy];tetracycline/ae [Adverse Drug Reaction];thiazide diuretic agent/ae [Adverse Drug Reaction];unindexed drug,"Jainkittivong, A.;Langlais, R. P.",1994,,,0,0,
2593,Pregnancy and delivery in a woman with Wilson's disease (degeneratio hepatoleuticularis). [Polish],"The authors present the course of two gestations and labours in women with Wilson's disease. Both patients were treated with D-penicillamine during pregnancy. As a result of their observations, the authors suggest that Wilson's disease requires proper diagnosis and cure before pregnancy and adequate care during pregnancy. In such a situation Wilson's disease should not be a high risk factor for pregnant women and their babies. It should be pointed out that undiagnosed Wilson's disease can be a cause of habitual abortion and infertility.",adult;article;case report;female;human;pregnancy;pregnancy complication/di [Diagnosis];pregnancy complication/dt [Drug Therapy];pregnancy outcome;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Pierzchala, W.;Zamlynski, J.;Rzempoluch, J.",1994,1994 Feb,,0,0,
2594,Motor impairment in Wilson's disease 3: The clinical impact of pyramidal tract involvement,"Magnetic brain stimulation was performed on 24 patients with Wilson's disease (WD). Responses to the right and left first dorsal interosseus muscle (FDI) and to the right and left tibialis anterior muscle (TA) were analysed. In 45% of the patients prolonged central motor conduction times (CCTs) to the FDIs were found, whereas only 12%, of the patients presented with prolonged CCTs to the TA muscles. No consistent significant correlations between copper metabolism and pyramidal tract function tested by magnetic brain stimulation were found. An improvement of CCTs and response amplitudes with copper elimination therapy was observed only at early phases of therapy. There was no correlation with duration of therapy or neurological symptoms. Thus magnetic brain stimulation turns out to be sensitive to detect subclinical pyramidal tract impairment in WD but seems to test a too specific aspect of motor impairment in WD to reflect the overall neurological status of the patients. Therefore, it has to be combined with other tests to be used for therapy control.",Central motor conduction time;Magnetic brain stimulation;Motor function;Wilson's disease;adolescent;adult;article;clinical article;clinical trial;controlled clinical trial;controlled study;female;human;magnetic field;male;motor control;oral drug administration;pyramidal tract;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Hefter, H.;Roick, H.;Van Giessen, H. J.;Arendt, G.;Weiss, P.;Stremmel, W.;Benecke, R.",1994,,,0,0,
2595,Theory and practice of psychopharmacogenetics,"This article attempts to elucidate the theory and practice of psychopharmacogenetics. Eight working models were identified and characterized with a distinct view of risk factors in the host, the pathophysiology of disease, and the strategies for optimum therapy. The biochemical culprits related to adverse drug reaction in each case can be used to identify a risk and thus contribute to prevention research. Since the phenomenology of these uncommon conditions covers a broad spectrum of neuropsychiatric manifestations, the insights they generated might presage a better understanding of the natural history of a wider range of mental disorders associated with genetic vulnerability. The emerging information suggests that psychopharmacogenetics could be defined from clinical perspectives as multidimensional analysis of genes, drugs, and behaviour for the treatment and prevention of psychiatric disorders.",practice;prevention;psychopharmacogenetics;theory;agitation;article;depression/si [Side Effect];genetic susceptibility;hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/et [Etiology];human;hypotension/et [Etiology];hypotension/si [Side Effect];individuality;mental disease/si [Side Effect];pathophysiology;pharmacogenetics;phenylketonuria/cn [Congenital Disorder];phenylketonuria/dt [Drug Therapy];phenylketonuria/et [Etiology];porphyria/dt [Drug Therapy];porphyria/et [Etiology];priority journal;psychopharmacology;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];debrisoquine/ae [Adverse Drug Reaction];debrisoquine/pd [Pharmacology];deferoxamine/dt [Drug Therapy];dopamine/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hematin/dt [Drug Therapy];hypnotic sedative agent/ae [Adverse Drug Reaction];hypnotic sedative agent/pd [Pharmacology];iron/ec [Endogenous Compound];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/pd [Pharmacology];penicillamine/dt [Drug Therapy];phenylalanine/ec [Endogenous Compound];porphyrin/ec [Endogenous Compound];psychotropic agent/ae [Adverse Drug Reaction];psychotropic agent/pd [Pharmacology];serotonin/ec [Endogenous Compound],"Tu, J. B.",1994,,http://dx.doi.org/10.1002/ajmg.1320540420,0,0,
2596,Current status of orphan disease drug development,The Orphan Drug Act has successfully stimulated the production of many orphan products for a number of orphan diseases. The success of its exclusive marketing provision in bringing otherwise unprofitable products to market has attracted the attention of manufacturers who use this provision to gain a monopoly for products with much larger annual sales than were contemplated by the original legislation. Corrective legislation to close this loophole is being prepared for introduction to Congress.,anemia/dt [Drug Therapy];blepharospasm/dt [Drug Therapy];cerebral palsy/dt [Drug Therapy];drug cost;drug industry;drug legislation;dysphonia/dt [Drug Therapy];enzyme deficiency/dt [Drug Therapy];enzyme replacement;Gaucher disease/dt [Drug Therapy];hirsutism/dt [Drug Therapy];human;priority journal;review;rosacea/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];alglucerase/dt [Drug Therapy];botulinum toxin A/dt [Drug Therapy];cyproterone acetate/dt [Drug Therapy];metronidazole/dt [Drug Therapy];orphan drug;pegademase/dt [Drug Therapy];penicillamine/dt [Drug Therapy];recombinant erythropoietin/dt [Drug Therapy];trientine/dt [Drug Therapy],"Thoene, J. G.",1994,,,0,0,
2597,Presymptomatic testing in families with Wilson's disease [7],,adolescent;case report;family study;gene locus;genetic linkage;human;letter;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Schwab, S. G.;Scherer, J.;Wildenauer, D. B.",1994,,http://dx.doi.org/10.1016/S0140-6736%2894%2993089-9,0,0,
2598,Pregnancy in a patient with Wilson's disease treated with D-penicillamine and zinc sulfate - A case report and review of the literature,"A case of successful pregnancy in a patient with Wilson's disease treated with D-penicillamine and zinc sulfate is presented. Experience with D-penicillamine, triethylene tetramine dihydrochloride (trien) and zinc salts during pregnancy is reviewed and discussed.",D-penicillamine;Pregnancy;Therapy;Wilson's disease;Zinc;adult;article;bioaccumulation;case report;copper blood level;female;human;liver;priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/dt [Drug Therapy],"Hartard, C.;Kunze, K.",1994,,,0,0,
2599,Hepatic disease and psychiatric illness: Relationships and treatment,"A relationship between hepatic diseases and psychiatric symptoms has long been speculated. While liver detoxication makes the exogenous substances harmless for the body, there are occasions where the liver may convert a harmless substance into a more toxic substance. With such an important role, the liver protects all the organs of the body. When liver is malfunctioning, toxic metabolites injurious to the brain may be produced. As the brain receives a high blood supply, a large amount of metabolites reach this organ. Hence, the metabolic function of the liver keeps a delicate reciprocal relationship between the two organs. In addition, a number of psychiatric medications affect liver functions. Another perplexing clinical problem is the difficulty in treating psychiatric symptoms in patients with liver disease. For example, benzodiazepines which do not affect the liver function in physically healthy psychiatric patients, may induce hepatic coma in patients with liver disease. Benzodiazepine antagonists produce dramatic and temporary improvement in patients with hepatic coma. Clinically, many psychoactive drugs produce hepatic complications. The very same drugs which produce hepatic side effects are required for the treatment of psychiatric symptoms in patients with hepatic disorders. To appropriately handle these situations, a thorough knowledge of the side effects of these drugs is necessary.",Antidepressants in liver disease;Benzodiazepines and liver disease;Hepatic encephalopathy;Liver disease and psychosis;Neuroleptics and liver disease;Posthepatitis syndrome;alcohol liver disease/et [Etiology];detoxification;disease association;drug blood level;drug metabolism;hepatic coma/si [Side Effect];hepatic encephalopathy/dt [Drug Therapy];hepatic encephalopathy/si [Side Effect];hepatitis/et [Etiology];hepatitis/si [Side Effect];human;jaundice/si [Side Effect];liver cirrhosis/et [Etiology];liver disease/et [Etiology];liver disease/si [Side Effect];liver failure/et [Etiology];liver metabolism;liver toxicity/si [Side Effect];mental disease/co [Complication];mental disease/dt [Drug Therapy];neuropsychiatry;review;Reye syndrome/et [Etiology];Reye syndrome/si [Side Effect];virus hepatitis/et [Etiology];Wilson disease/et [Etiology];4 aminobutyric acid/ec [Endogenous Compound];acetylsalicylic acid/ae [Adverse Drug Reaction];ammonia/ec [Endogenous Compound];anticonvulsive agent/ae [Adverse Drug Reaction];anxiolytic agent/ae [Adverse Drug Reaction];anxiolytic agent/dt [Drug Therapy];barbituric acid derivative/it [Drug Interaction];barbituric acid derivative/pd [Pharmacology];benzodiazepine derivative/ae [Adverse Drug Reaction];benzodiazepine derivative/cr [Drug Concentration];benzodiazepine derivative/dt [Drug Therapy];benzodiazepine derivative/ec [Endogenous Compound];benzodiazepine receptor;benzodiazepine receptor blocking agent/dt [Drug Therapy];benzodiazepine receptor stimulating agent/dv [Drug Development];carbamazepine/cr [Drug Concentration];carbamazepine/it [Drug Interaction];chlorpromazine/ae [Adverse Drug Reaction];chlorpromazine/pd [Pharmacology];cimetidine/cb [Drug Combination];cimetidine/it [Drug Interaction];diazepam/it [Drug Interaction];flumazenil/dt [Drug Therapy];fluoxetine/it [Drug Interaction];fluoxetine/pd [Pharmacology];fluvoxamine/it [Drug Interaction];haloperidol/ae [Adverse Drug Reaction];imipramine/ae [Adverse Drug Reaction];neuroleptic agent/ae [Adverse Drug Reaction];neuroleptic agent/cr [Drug Concentration];neuroleptic agent/it [Drug Interaction];paroxetine/cb [Drug Combination];paroxetine/cr [Drug Concentration];paroxetine/it [Drug Interaction];paroxetine/pd [Pharmacology];phenothiazine derivative/ae [Adverse Drug Reaction];psychotropic agent/ae [Adverse Drug Reaction];psychotropic agent/dt [Drug Therapy];serotonin uptake inhibitor/cb [Drug Combination];serotonin uptake inhibitor/it [Drug Interaction];sertraline/it [Drug Interaction];toxin/to [Drug Toxicity];trazodone/it [Drug Interaction];tricyclic antidepressant agent/ae [Adverse Drug Reaction];tricyclic antidepressant agent/cr [Drug Concentration];tricyclic antidepressant agent/it [Drug Interaction];unindexed drug;valproic acid/ae [Adverse Drug Reaction];zinc/dt [Drug Therapy],"Ananth, J.;Swartz, R.;Burgoyne, K.;Gadasally, R.",1994,,,0,0,
2600,Dangers of interrupting decoppering treatment in Wilson's disease [1],,blood brain barrier;copper blood level;drug monitoring;esophagus hemorrhage/si [Side Effect];hepatitis/si [Side Effect];human;letter;liver failure/si [Side Effect];oral drug administration;patient compliance;priority journal;urinary excretion;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/to [Drug Toxicity];copper/ec [Endogenous Compound];copper 64;metallothionein/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/ad [Drug Administration];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy],"Hoogenraad, T. U.;Lang, C. J. G.;Rabas-Kolominsky, P.;Engelhardt, A.;Konig, H. J.",1994,,,0,0,
2601,"Wilson's disease. Physiopathology, therapeutic approach and clinical contribution. [Italian]","Wilson's disease is an hereditary recessive autosomal disorder which affects around five people per million inhabitants. The primary defect is localized in the liver and the disease is manifested by the accumulation of copper in tissues. The diminution of ceruloplasmin, which until a few years ago was mistakenly thought to be the pathogenetic cause of Wilson's disease, is an epiphenomenon of the underlying metabolic defect characterized by defective copper biliary excretion. There are four stages in the natural history of the disease: 1) an asymptomatic stage of hepatic copper accumulation; 2) dismission and redistribution of copper leading to hepatocellular necrosis and hemolysis; 3) extrahepatic accumulation of copper leading to the onset of cirrhosis and neurological damage; 4) stage of homeostasis following treatment but with possible irreversible neurological damage. Treatment of Wilson's diseases takes the form of pharmacological, dietary and surgical therapy. Through the formation of copper and protein metal complexes D-penicillamine impoverishes copper deposits causing the reduction or disappearance of hepatic and neurological symptoms; a small percentage of patients treated develops a nephrotic syndrome requiring the compulsory suspension of the drug. In this case a valid alternative is triethylentetramine dichloridrate (TETA) which provokes increased cupremia during cupruresis. The response to pharmacological treatment is better the earlier treatment is started and the more regular its administration. Dietary intake of copper must be reduced in parallel avoiding foods with a high copper content. Liver transplant obviously leads to the 'resolution' of the underlying metabolic problem in patients who develop fulminating hepatitis with hypercupremia and hemolysis and, of course, in cases of uncompensated cirrhosis which do not respond to kelating therapy. Lastly, the authors describe the case of a young man suffering from first stage Wilson's disease who developed a severe nephrotic syndrome following D-penicillamine therapy; the new TETA therapy is better tolerated and the patient is today continuing to keep the disease in good functional compensation.",D-penicillamine;triethylentetramine dichloridrate;Wilson's disease;adult;article;case report;complex formation;diet;human;liver cirrhosis;male;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Gallo, V.;Riva, P.;Sidoli, L.;Bisbocci, D.",1994,,,0,0,
2602,Development of neurologic symptoms in a patient with asymptomatic Wilson's disease treated with penicillamine,"Objective: To report a case of presymptomatic Wilson's disease in a patient who became severely neurologically disabled after treatment with penicillamine and to discuss alternative initial therapy for such patients. Design: Case report. The patient described is briefly compared with a previously studied group of 13 similar presymptomatic patients who received zinc therapy without any clinical worsening and who have had 3 to 9 years of follow-up. Setting: Referral hospital. Patients: The patient was referred to us. Intervention: The patient had initially been treated with penicillamine. Main Outcome Measure: The main outcome of interest is permanent neurologic disability, depending on type of initial treatment. Results: The result of initial penicillamine therapy in the patient described is permanent neurologic disability. This is believed to be due to mobilization and redistribution of hepatic copper causing high levels of copper in key areas of the brain. Conclusion: We conclude that penicillamine used as initial therapy, even in patients with neurologically asymptomatic Wilson's disease, increases the risk of inducing permanent neurologic damage.",adult;article;brain tissue;case report;copper metabolism;disability;disease course;dysarthria/si [Side Effect];human;liver metabolism;male;neurologic disease/si [Side Effect];neurological complication;priority journal;rigidity;tissue distribution;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];zinc acetate/do [Drug Dose];zinc acetate/dt [Drug Therapy];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy],"Brewer, G. J.;Turkay, A.;Yuzbasiyan-Gurkan, V.",1994,,,0,0,
2603,Wilson's disease: MRI with clinical correlation,"We tried to establish possible correlations between clinical data and MRI in a group of patients with Wilson's disease. Eleven patients (6 male, 5 female), aged between 11 and 50 years old, with a duration of illness from 5 months to 32 years, were submitted to MRI on a 1.5 T System. Three patients were asymptomatic, two had mild neurological disturbances, two were moderately affected and the remaining four had a severe form of the disease. All were receiving D-penicillamine at the time of the study. In the most symptomatic patients there were abnormalities in five or more sites on MRI. The putamen was affected in all symptomatic patients, including five with dystonia. A striking feature was the peripheral location of high signal putaminal lesions on T2-weighted images. In five cases, lesions in the corpus striatum or substancia nigra explained the patient's Parkinsonian features. MRI is an efficient method for studying involvement of the central nervous system in Wilson's disease, and allows some interesting anatomoclinical correlations.",mri;Wilson's disease;adolescent;adult;article;child;clinical article;clinical feature;corpus striatum;disease duration;disease severity;dystonia;female;human;male;neurologic disease;neuroradiology;nuclear magnetic resonance imaging;parkinsonism;priority journal;putamen;school child;substantia nigra;symptom;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Magalhaes, A. C. A.;Caramelli, P.;Menezes, J. R.;Lo, L. S.;Bacheschi, L. A.;Barbosa, E. R.;Rosemberg, L. A.;Magalhaes, A.",1994,,,0,0,
2604,Measurement of blood holoceruloplasmin by EIA using a mouse monoclonal antibody directed to holoceruloplasmin: Implication for mass screening of Wilson disease,,autosomal recessive disorder/cn [Congenital Disorder];biliary excretion;blood sampling;conference paper;electroimmunoassay;human;human experiment;liver cell;mass screening;normal human;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];monoclonal antibody;penicillamine/dt [Drug Therapy];plasmin/ec [Endogenous Compound];trientine/dt [Drug Therapy],"Endo, F.;Taketa, K.;Nakamura, K.;Awata, H.;Tanoue, A.;Eda, Y.;Matsuda, I.",1994,,,0,0,
2605,Wilson's disease presenting as symptomatic urolithiasis: A case report and review of the literature,"Wilson's disease is a rare autosomal recessive disorder that typically presents as hepatic, neurological or psychiatric illness in late adolescence and early adulthood. Although urolithiasis has been documented in as many as 16% of patients with Wilson's disease, only 3 cases have been described that presented with stone disease. We report on a healthy 17-year-old girl who presented with renal colic and a distal ureteral calculus that was subsequently passed. The patient was hospitalized 2 months later with jaundice, ascites, hyperchloremic metabolic acidosis and elevated hepatic enzymes. She was hypophosphatemic and hypouricemic with a low serum ceruloplasmin. Diagnosis was Wilson's disease with Fanconi's syndrome, but despite penicillamine therapy and intensive care support rapidly progressive hepatic failure, coagulopathy and encephalopathy developed. The patient died before emergency liver transplantation. Our case illustrates the role urologists may have in the diagnosis of this rare but potentially treatable disease. Wilson's disease should be considered in the differential diagnosis of any adolescent or young adult with urolithiasis.",Fanconi syndrome;hepatolenticular degeneration;liver;urinary calculi;adolescent;article;ascites;blood clotting disorder;brain disease;case report;clinical feature;differential diagnosis;Fanconi renotubular syndrome;female;human;hyperchloremia;jaundice;kidney colic;liver failure;priority journal;ureter stone;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Nakada, S. Y.;Brown, M. R.;Rabinowitz, R.",1994,,,0,0,
2606,At long last: An animal model of Wilson's disease,,animal model;animal tissue;autosomal recessive inheritance;chromosome 13q;chronic hepatitis;hepatitis;liver carcinogenesis;nonhuman;note;priority journal;rat;Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Sokol, R. J.",1994,,http://dx.doi.org/10.1016/0270-9139%2894%2990211-9,0,0,
2607,Dermatomyositis and Wilson's disease. [French],A 15 year-old girl developed both a dermatomyositis and a Wilson's disease. A clinical remission was obtained with steroids and D-penicillamine. The potential role of cupric intoxication in the pathogeny of the muscular syndrome is discussed,adolescent;article;case report;controlled study;dermatomyositis/co [Complication];dermatomyositis/dt [Drug Therapy];female;human;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy],"El Alaoui-Faris, M.;Benabdeljalil, M.;Slassi, I.;Boutchiche, M.;Birouk, N.;Belaidi, H.;Saidi, A.;Chkili, T.",1994,,,0,0,
2608,Wilson's disease: Contrast enhancement of cerebral lesions on MR images after penicillamine therapy [14],,adolescent;brain disease/di [Diagnosis];brain edema;case report;clinical trial;contrast enhancement;drug hypersensitivity/si [Side Effect];dysarthria/si [Side Effect];dystonia/si [Side Effect];extrapyramidal symptom;female;human;letter;liver dysfunction;muscle rigidity/si [Side Effect];nuclear magnetic resonance imaging;priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Sener, R. N.",1994,,,0,0,
2609,Direct transfer of copper from metallothionein to superoxide dismutase: A possible mechanism for differential supply of Cu to SOD and ceruloplasmin in LEC rats,"Copper (Cu) and zinc (Zn)-binding superoxide dismutase (Cu,Zn-SOD) is synthesized always in a form of holo-protein in the liver of LEC rats, a genetically disordered mutant strain in Cu metabolism which accumulates Cu in a form bound to metallothionein (MT). On the other hand, ceruloplasmin (Cp) is synthesized in the liver and excreted into the blood plasma mostly as an apo-protein before the onset of acute hepatitis, and then holo-form at the onset of jaundice. Thus, Cu is supplied differentially between Cp and SOD, and at different times, i.e., before and at the onset of acute hepatitis. Availability of Cu to apo-SOD was examined to explain the mechanisms for the differential supply of Cu among three different Cu forms; i) cuprous ion bound to glutathione, ii) free cupric ion, and iii) cuprous ion bound to MT. Cu was transferred to SOD from the three Cu complexes though MT-bound Cu was a less efficient Cu source to apo-SOD. The results indicate that SOD is always present in a holo-form in LEC rats because even MT-bound Cu can be supplied to SOD, while Cp is present in an apo-form because Cu is sequestered to MT and not available in free ionic forms in LEC rats before the onset of acute hepatitis.",acute hepatitis;animal experiment;animal model;animal tissue;article;controlled study;copper deficiency/cn [Congenital Disorder];copper metabolism;enzyme activity;enzyme defect;enzyme polymorphism;jaundice;Menkes syndrome/cn [Congenital Disorder];nonhuman;priority journal;rat;Wilson disease/cn [Congenital Disorder];apoprotein;ceruloplasmin;copper;metallothionein;superoxide dismutase;zinc,"Suzuki, K. T.;Kuroda, T.",1994,,,0,0,
2610,Chiral cognisance: A road to safer and more effective medicinal products,"A quarter of all synthetic medicinal drugs contain a mixture of equal proportions of two molecules that have the same chemical constitution but differ in the spatial arrangement of their constituent atoms such that each is a mirror-image of the other, like the right and left hand. Biologically, receptors which are stereospecific react with only one of the two components of the mixture to produce the desired therapeutic effect, while the other is inactive or may interact with different receptors to cause undesirable, even toxic, effects. Development of syntheses that produce a preponderance of the required form, and efficient separation of mixtures, will result in safer and more effective medicinal products.",agranulocytosis/si [Side Effect];chirality;drug design;drug marketing;drug receptor binding;enantiomer;neurotoxicity/si [Side Effect];Parkinson disease/dt [Drug Therapy];pyridoxine deficiency/si [Side Effect];racemic mixture;rheumatic disease/dt [Drug Therapy];short survey;stereoisomerism;stereospecificity;Wilson disease/dt [Drug Therapy];antitussive agent;dextropropoxyphene;dextrorphan;levodopa/ae [Adverse Drug Reaction];levodopa/dt [Drug Therapy];levodopa/pd [Pharmacology];levopropoxyphene;levorphanol;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];unclassified drug,"Ariens, E. J.;Wuis, E. W.",1994,,,0,0,
2611,Selective enhancement of metallothionein mRNA expression by copper in primary cultured liver parenchymal cells of LEC rats,"Mechanisms for the abnormal copper (Cu) accumulation in the liver of LEC rats were examined using primary cultured liver parenchymal cells prepared from mutant LEC rats and those from control LEA rats (original strain). The Cu and metallothionein (MT) mRNA levels in the liver of LEC rats were caused to decrease to the same levels as those of LEA rats by removing Cu in vivo selectively with tetrathiomolybdate. Cu was taken up by LEC rat cells to the same extent as LEA rat cells by exposure to low medium Cu and to a higher extent by exposure to high medium Cu, while the MT mRNA level in LEC rat cells increased dose-dependently at a much higher rate than that in LEA rats. MT mRNA levels in both cells were comparable by exposure to cadmium, zinc and dexamethazone. The results indicate that expression of MT mRNA is selectively enhanced by Cu in LEC cells despite the fact that uptake of Cu is comparable with normal cells.",animal cell;animal experiment;animal model;animal tissue;article;controlled study;copper metabolism;dose response;gene expression;liver cell culture;male;nonhuman;priority journal;rat;Wilson disease;copper/pd [Pharmacology];metallothionein/ec [Endogenous Compound],"Kanno, S.;Suzuki, J. S.;Aoki, Y.;Suzuki, K. T.",1994,,,0,0,
2612,Thiotungstate-copper interactions II. The effects of tetrathiotungstate on systemic copper metabolism in normal and copper-treated rats,"The intraperitoneal administration of tetrathiotungstate to rats (6-17.4 mg W/Kg BW) caused profound changes in copper metabolism in both normal rats and in rats pretreated with copper. Plasma copper associated with albumin increased, liver copper, particularly cytosol copper, was depleted, and biliary excretion was increased. There was also a movement of copper to higher molecular weight proteins in both liver cytosol and bile. In contrast to penicillamine, tetrathiotungstate did not increase liver cytosolic apometallothionein levels and reduced the rise provoked by copper. Metallothionein-bound copper was removed. Ceruloplasmin oxidase activity was inhibited and there was evidence for increased movement of copper into subcellular organelles, probably lysosomes. It is concluded that tetrathiotungstate has a genuine 'decoppering' effect and could be considered as an alternative to thiomolybdates in the treatment of copper storage diseases.",albumin blood level;animal cell;animal model;animal tissue;article;biliary excretion;controlled study;copper blood level;copper metabolism;enzyme inhibition;intraperitoneal drug administration;intravenous drug administration;liver clearance;male;molecular weight;nonhuman;rat;Wilson disease/et [Etiology];albumin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper complex/an [Drug Analysis];copper complex/cm [Drug Comparison];copper complex/dv [Drug Development];copper complex/it [Drug Interaction];copper complex/pd [Pharmacology];larocop;metallothionein/ec [Endogenous Compound];methionine copper;oxidoreductase/ec [Endogenous Compound];penicillamine/cm [Drug Comparison];penicillamine/pd [Pharmacology];tetrathiotungstic acid/an [Drug Analysis];tetrathiotungstic acid/cm [Drug Comparison];tetrathiotungstic acid/dv [Drug Development];tetrathiotungstic acid/it [Drug Interaction];tetrathiotungstic acid/pd [Pharmacology];thiomolybdic acid/cm [Drug Comparison];thiomolybdic acid/pd [Pharmacology];unclassified drug,"McQuaid, A.;Lamand, M.;Mason, J.",1994,,http://dx.doi.org/10.1016/0162-0134%2894%2980005-7,0,0,
2613,Thiotungstate-copper interactions I. Studies on the metabolism of [<sup>185</sup>W] tetrathiotungstate and the systemic interactions of labeled pharmacological doses with copper in rats,"[<sup>185</sup>W] tetrathiotungstate was employed to study the metabolism of thiocompounds in rats after i.v. injection. At tracer levels (12.5 mug W) the most important plasma binding protein eluted in the position of ceruloplasmin but the association did not prevent uptake of thiotungstate by the liver. At higher dose levels (1.5 mg W) there was considerable hydrolysis immediately after injection with rapid excretion of label in urine. The [<sup>185</sup>W] tetrathiotungstate remaining in plasma was associated with albumin and the amount retained was increased by pretreatment of the rats with copper. The increased binding to albumin did not prevent hepatic uptake and over the short-term pretreatment with copper increased the movement of the isotope into subcellular organelles, probably lysosomes. The excretion in bile was increased and the label was associated with high molecular weight proteins. In liver cytosol the <sup>185</sup>W was bound by specific, as yet uncharacterized, proteins. At the higher dose levels there was some movement to higher molecular weight proteins and this was greatly increased by the pretreatment with copper. The studies show that the metabolism of <sup>185</sup>W tetrathiotungstate is sufficiently similar to <sup>99</sup>Mo or <sup>35</sup>S tetrathiomolybdate for work on the systemic interactions of thiocompounds and copper in man and animals.",animal cell;animal experiment;animal tissue;article;biliary excretion;ceruloplasmin blood level;controlled study;copper metabolism;drug labeling;drug metabolism;intravenous drug administration;male;nonhuman;protein binding;rat;Wilson disease/et [Etiology];copper/it [Drug Interaction];copper/pk [Pharmacokinetics];copper/pd [Pharmacology];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/it [Drug Interaction];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology];tetrathiotungstic acid/cm [Drug Comparison];tetrathiotungstic acid/dv [Drug Development];tetrathiotungstic acid/it [Drug Interaction];tetrathiotungstic acid/pk [Pharmacokinetics];tetrathiotungstic acid/pd [Pharmacology];tracer/cm [Drug Comparison];tracer/pk [Pharmacokinetics];tracer/pd [Pharmacology];tungsten/cm [Drug Comparison];tungsten/dv [Drug Development];tungsten/it [Drug Interaction];tungsten/pk [Pharmacokinetics];tungsten/pd [Pharmacology];unclassified drug,"McQuaid, A.;Lamand, M.;Mason, J.",1994,,http://dx.doi.org/10.1016/0162-0134%2894%2980004-9,0,0,
2614,"The LEC rat: A model for human hepatitis, liver cancer, and much more","The LEC rat is an inbred mutant strain with spontaneous hepatitis isolated from Long-Evans rats. Since approximately 40% of LEC rats die of fulminant hepatitis, the rat serves an animal model for studying the pathogenesis and treatment of human fulminant hepatitis. The remaining 60% of LEC rats survive and develop chronic (prolonged) hepatitis and subsequently develop liver cancer. Therefore, the LEC rat serves an important animal model for studying the significance of chronic hepatitis in the development of human liver cancer, which often develops in association with chronic hepatitis. The LEC rat can also be used as an animal model of Wilson's disease, since recent studies have disclosed high copper accumulation in the liver and low ceruloplasmin concentration in the serum of this mutant rat.",animal model;chronic hepatitis;copper metabolism;enzyme blood level;hepatitis;histochemistry;liver cancer/co [Complication];liver carcinogenesis;nonhuman;oncogene c myc;oncogene ras;priority journal;rat;review;Wilson disease/di [Diagnosis];8 hydroxyguanine/ec [Endogenous Compound];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;DNA/ec [Endogenous Compound];penicillamine;trientine,"Mori, M.;Hattori, A.;Sawaki, M.;Tsuzuki, N.;Sawada, N.;Oyamada, M.;Sugawara, N.;Enomoto, K.",1994,,,0,0,
2615,Penicillamin-induced Elastosis perforans serpiginosa. [German],Elastosis perforans serpiginosa is a rare disease with variable etiology. We report on a 33-year-old male patient in whom the disease was induced by long-term treatment with the chelating agent D-penicillamine.,D-penicillamine;elastosis perforans serpiginosa;Wilson disease;adult;article;case report;elastosis/si [Side Effect];human;human tissue;male;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Wilhelm, K. P.;Wolff, H. H.",1994,,,0,0,
2616,Excessive iron storage in a patient with Wilson's disease,"We report on an otherwise healthy female, mother of two children, with severe decompensated liver cirrhosis due to an iron overload and Wilson's disease. The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. The case is interesting because of the coincidence of Wilson's disease and excessive iron storage.",copper;ferritin;hemochromatosis;iron;Wilson's disease;adult;article;case report;female;human;iron storage;oral drug administration;Wilson disease/su [Surgery];ferritin/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Hafkemeyer, P.;Schupp, M.;Storch, M.;Gerok, W.;Haussinger, D.",1994,,,0,0,
2617,Wilson's disease detected by acute hemolysis in a 10-year-old girl. [French],,article;case report;female;genetic disorder;hemolysis;human;liver disease;neuropathy;oral drug administration;school child;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Klink, R.;Adafer, M.;Yassine, B.;Bernard, D.;Lajarrige, C.;Kremp, L.;Broue, P.",1993,,,0,0,
2618,Wilson's disease: A case review. [Italian],,article;clinical article;copper metabolism;human;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];penicillamine/dt [Drug Therapy],"Trallori, G.;Bardazzi, G.;Bonanomi, A. G.;De Cecco, A.;D'Albasio, G.;Bartoletti, L.;Pacini, F.;Morettini, A.",1993,,,0,0,
2619,Wilson's disease and catatonia,"A 12-year-old Indian boy presented to a psychiatric unit with catatonia. He was subsequently diagnosed to have Wilson's disease. Symptoms improved on treatment with penicillamine, zinc sulphate, and benzodiazepines.",article;case report;catatonia;human;male;oral drug administration;priority journal;school child;Wilson disease/dt [Drug Therapy];benzodiazepine/dt [Drug Therapy];diazepam/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Davis, E. J. B.;Borde, M.",1993,,,0,0,
2620,Zinc and macular degeneration [2],,bone marrow depression;copper blood level;letter;priority journal;retina macula degeneration/et [Etiology];sideroblastic anemia;Wilson disease;zinc blood level;zinc/ec [Endogenous Compound],"Beaumont, P.;Trempe, C. L.;Newsome, D. A.",1993,,,0,0,
2621,Orthotopic liver transplantation for hepatic complications of Wilson's disease,"Thirteen orthotopic liver transplantations were performed in 12 patients for hepatic complications of Wilson's disease between May 1988 and July 1992. Ten patients had fulminant hepatic failure and two chronic liver disease. One patient underwent retransplantation for liver abscess secondary to hepatic artery thrombosis. Nine patients survive at a median follow-up of 18 (range 6-31) months. Three patients have died: two from multiple organ failure and sepsis, one from B cell lymphoma. Postoperative complications included bleeding requiring laparotomy in two patients, renal impairment in five, bacterial septicaemia in three, fungal sepsis in two and acute cellular rejection in six. The nine surviving patients are well with normal liver function test results.",adolescent;adult;article;clinical article;complication;evaluation and follow up;female;human;liver transplantation;male;priority journal;school child;Wilson disease/dt [Drug Therapy];azathioprine;cyclosporin;penicillamine/dt [Drug Therapy];prednisolone;tacrolimus;trientine/dt [Drug Therapy],"Rela, M.;Heaton, N. D.;Vougas, V.;McEntee, G.;Gane, E.;Farhat, B.;Chiyende, J.;Mieli-Vergani, G.;Mowat, A. P.;Portmann, B.;Williams, R.;Tan, K. C.",1993,,,0,0,
2622,What is your diagnosis? Wilson's disease (hepatolenticular degeneration). [German],,adult;article;case report;cognitive defect/et [Etiology];human;male;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Keller, D. H.",1993,23 Mar,,0,0,
2623,A mutant mouse (tx) with increased hepatic metallothionein stability and accumulation,"Metallothioneins (MTs) are low-molecular-mass cysteine-rich proteins implicated in metal homoeostasis and resistance to toxicity induced by heavy metals and alkylating agents. We report high hepatic MT protein accumulation (greater than 100-fold compared with wild-type mice) in toxic milk (tx) mice, along with markedly higher cytosol copper and zinc levels. Increased MT-gene transcription alone could not account for the high constitutive MT protein levels, since MT mRNA levels were not increased in tx mouse livers. However, hepatic MT was significantly more stable in adult tx mice: MT half-life (t( 1/2 )) was 79 or 77% greater than in wild-type mice before and after Cd induction respectively. Cd or Zn treatment increased MT mRNA, but not MT protein, accumulation in tx mouse livers: Cd displaced MT-bound Zn and Cu in preexisting MT. Thus tx mice appear to accumulate hepatic MT as a result of decreased protein degradation. These animals may provide a useful model to study the physiological role of MT, and human diseases (such as Wilson's disease) with abnormal copper metabolism.",animal experiment;animal model;animal tissue;article;cell level;controlled study;copper metabolism;female;genetic transcription;half life time;homeostasis;liver;male;Menkes syndrome;mouse;mutant;nonhuman;priority journal;protein degradation;protein stability;Wilson disease;alkylating agent/to [Drug Toxicity];cadmium/to [Drug Toxicity];copper/ec [Endogenous Compound];heavy metal/to [Drug Toxicity];messenger RNA/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Koropatnick, J.;Cherian, M. G.",1993,,,0,0,
2624,"Zinc-induced metallothionein and copper metabolism in intestinal mucosa, liver, and kidney of rats","Large doses of parenteral zinc (Zn) and/or the feeding of high Zn diets to animals or humans for long periods affects copper (Cu) metabolism. Previous work suggests that Zn-induced metallothionein (MT) in intestinal epithelial cells binds Cu and inhibits its absorption. This study was designed to determine the effects of treating rats with high dietary or parenteral Zn on Cu metabolism and its relationship to MT in the intestinal epithelium, liver and kidney. Six-week-old male rats were fed for one week a control diet containing 42 mg Zn and 6 mg Cu/kg. They were then divided into the three groups. One group continued to receive the control diet while another received a similar diet containing 560 mg Zn/kg. A third group, fed the control diet, received a subcutaneous dose of 90 mg Zn/kg body weight every 2-3 days for the duration of the experiment. Rats from each group were killed on days 7 and 14. Low Cu status in Zn-treated rats was indicated by lower than normal serum Cu concentration, serum ceruloplasmin activity, low liver and kidney Cu concentrations and low cytochrome C oxidase activity. None of these changes, however, were related to an increase in Cu as a result of Zn- induced MT in the intestinal epithelial cell. Instead, as the MT concentrations rose, Cu concentration decreased. This study suggests that the effects of high Zn treatment on Cu status are not the result of the long- held theory that Zn-induced intestinal MT sequesters Cu and prevents its passage to the circulation. Instead, it may be caused by a direct effect of high lumenal Zn concentrations on Cu transport into the epithelial cell.",Absorption;Copper;Intestine;Kidney Liver;Metallothionein;Rat;Zinc;animal experiment;animal model;animal tissue;article;ceruloplasmin blood level;controlled study;copper metabolism;dietary intake;dose response;drug effect;enzyme activity;intestine epithelium cell;intestine mucosa;kidney;liver;male;nonhuman;oral drug administration;priority journal;subcutaneous drug administration;tissue level;Wilson disease;ceruloplasmin/ec [Endogenous Compound];copper/pd [Pharmacology];cytochrome c oxidase/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];zinc/ad [Drug Administration];zinc/do [Drug Dose];zinc/pd [Pharmacology],"Reeves, P. G.;Rossow, K. L.;Bobilya, D. J.",1993,,http://dx.doi.org/10.1016/S0271-5317%2805%2980791-2,0,0,
2625,Metabolic effects of liver transplantation in Wilson's disease,,adult;clinical article;conference paper;copper metabolism;cornea disease/co [Complication];female;functional assessment;graft rejection/dt [Drug Therapy];graft rejection/pc [Prevention];human;liver transplantation;male;neurological complication/co [Complication];priority journal;secondary amenorrhea/co [Complication];Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cyclosporin/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Chen, C. L.;Kuo, Y. C.",1993,,,0,0,
2626,Progression prevention in chronic liver diseases. [German],,cholestasis/dt [Drug Therapy];chronic liver disease/dt [Drug Therapy];chronic liver disease/th [Therapy];conference paper;hepatitis/dt [Drug Therapy];human;liver cirrhosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];aciclovir/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];azathioprine/dt [Drug Therapy];colchicine;deferoxamine/dt [Drug Therapy];enzyme inhibitor;ganciclovir/dt [Drug Therapy];glucocorticoid;glycyrrhetinic acid;malotilate;penicillamine/dt [Drug Therapy];prostaglandin e derivative/dt [Drug Therapy];s adenosylmethionine;silymarin;unclassified drug;ursodeoxycholic acid/dt [Drug Therapy],"Boker, K. H. W.;Manns, M. P.",1993,,,0,0,
2627,Cranial MRI in hepatic disease -Relationship between MR imaging and clinical symptoms and laboratory analysis of liver function,"Magnetic resonance imaging studies on 12 cases with hepatic disease were performed. In 11 adult patients with chronic hepatic failure, T<inf>1</inf>-weighted images demonstrated increased signal in the globus pallidus in 7 patients (63.6%) and in some parts of the cerebral peduncles in 6 patients (54.5%), in the substantia innominata in 4 patients (36.3%). There might be some correlation between the abnormality of MR imaging and clinical symptoms of hepatic encephalopathy. There was a significant correlation between the intensity of the signal and Fischer's ratio of amino acid analysis. In one patient with Wilson's disease, who developed symptoms of central nervous system, T<inf>1</inf>-weighted images demonstrated increased signal in the globus pallidus. After treatment of D-penicillamine, the signal of the globus pallidus decreased.",article;clinical article;controlled study;globus pallidus;hepatic encephalopathy/di [Diagnosis];human;liver disease/di [Diagnosis];nuclear magnetic resonance;peduncular ansa;Wilson disease/di [Diagnosis],"Iijima, M.;Kamitani, T.;Kamakura, K.;Nagata, N.;Tsuchiya, K.",1993,,,0,0,
2628,Magnetic resonance imaging of the brain in Wilson's disease,"Eight patients with Wilson's disease (WD) were studied by magnetic resonance imaging (MRI) of the brain; seven also underwent X-ray computed tomography (CT) of the brain. We describe the changes in the brain and try to correlate them with the clinical manifestations and progress of the disease. Six patients were symptomatic, with predominantly neurological problems. Two were asymptomatic, diagnosed upon screening siblings of index cases. Of the six symptomatic patients, five had basal ganglia lesions, combined in four with brain stem changes, in one with only brain stem abnormalities, clinical findings were minimal despite pronounced MRI changes. In three patients MRI abnormalities regressed following chelating therapy. MRI can contribute to documentation of early neurological involvement in WD, especially in patients with no abnormalities on CT. However, MRI changes may not correlate with clinical presentation or response to therapy.",Computed tomography;Hepatolenticular degeneration;Magnetic resonance imaging;Penicillamine;Wilson's disease;adolescent;adult;article;basal ganglion;brain stem;brain tomography;chelation therapy;clinical article;clinical feature;disease course;female;human;male;nuclear magnetic resonance imaging;priority journal;school child;sibling;thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];penicillamine/ae [Adverse Drug Reaction];trientine,"Nazer, H.;Brismar, J.;Al-Kawi, M. Z.;Gunasekaran, T. S.;Jorulf, K. H.",1993,,,0,0,
2629,Glycogen storage diseases and other metabolic liver diseases in infants and children. [German],,child;enzyme deficiency/dt [Drug Therapy];glycogen storage disease/di [Diagnosis];human;infant;liver cirrhosis;liver disease/di [Diagnosis];metabolic disorder/di [Diagnosis];short survey;Wilson disease/dt [Drug Therapy];cerebrosidase/dt [Drug Therapy];enzyme/dt [Drug Therapy];penicillamine/dt [Drug Therapy];unclassified drug,"Otting, U.;Hellmann, C.",1993,,,0,0,
2630,Nephrotic syndrome secondary to d-penicillamine in a patient with Wilson's disease. [Spanish],,adolescent;case report;chemically induced disorder;child;female;human;kidney disease;letter;male;proteinuria;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Castellvi Suana, J. M.;Xiol Quingles, X.;Castellote Alonso, J.;Guardiola Capon, J.",1993,Oct,,0,0,
2631,Zinc therapy in Wilson's disease. [Italian],,conference paper;human;Wilson disease/dt [Drug Therapy];zinc/dt [Drug Therapy],"Lassandro, F.;Rapuano, A.;Varone, A.",1993,,,0,0,
2632,Urinary copper excretion after penicillamine challenge in children with prolonged hepatitis A infection [1],,acute hepatitis;adolescent;case report;child;convalescence;differential diagnosis;female;hepatitis A/di [Diagnosis];hepatomegaly;human;jaundice;letter;male;priority journal;urinary excretion;Wilson disease;copper/ec [Endogenous Compound];penicillamine,"Gregorio, G. V.;Mieli-Vergani, G.",1993,,http://dx.doi.org/10.1016/0270-9139%2893%2990380-6,0,0,
2633,Wilson's disease: Current status,,ceruloplasmin blood level;clinical feature;copper blood level;familial disease;histopathology;human;liver transplantation;note;prevalence;priority journal;Wilson disease/di [Diagnosis];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine;trientine;zinc,"Crabtref, K.",1993,,,0,0,
2634,Wilson disease,,Penicillamine;Wilson disease;Zinc;genetic analysis;human;prenatal diagnosis;priority journal;review;serum;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];unithiol/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Houwen, R. H. J.;Van Hattum, J.;Hoogenraad, T. U.",1993,,,0,0,
2635,Erratum: Zinc in the treatment of Wilson's disease: How it works (Gastroenterology (May 1993) 104 (1566-1568)),,erratum;error;priority journal,"Yarze, J. C.;Friedman, L. S.",1993,,,0,0,
2636,Penicillamine-induced changes in elastic tissue of the upper respiratory tract,"We describe a patient who developed upper respiratory tract symptoms following long-term treatment of Wilson's disease with penicillamine. These symptoms were attributed to areas of pharyngeal thickening and were treated with a laser. Histological examination of the lesions showed proliferations of abnormal elastic fibres similar to those previously described at other sites, especially the skin, in patients receiving penicillamine, This drug impairs the maturation and reduces the stability of elastic fibres and although elastic tissue throughout the body is affected, we are aware of no previous reports of penicillamine-induced changes presenting with upper respiratory tract symptoms.",Penicillamine complications;Wilson's disease;adult;article;case report;complication;elastic fiber;elastic tissue;histology;human;laser surgery;male;maturation;priority journal;skin;skinfold;upper respiratory tract;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Babu Manohar, M.;Boldy, D. A. R.;Bryan, R. L.;Pearman, K.",1993,,,0,0,
2637,Zinc treatment of Wilson's disease. Five cases. [French],"Zinc treatment of Wilson's disease was introduced by Schouwink in 1961 and is still uncommon in France. We evaluated the effectiveness and safety of zinc in 5 patients with Wilson's disease aged from 19 to 40 years. There were three neurological, one hepatic and one asymptomatic cases. Zinc was administered in doses of 120 to 272 mg/day, alone in 3 cases and combined with D-penicillamine in 2 cases. After 1 to 7 years of zinc therapy, our experience is consistent with data from recent literature and provides further evidence of zinc effectiveness. Zinc may be prescribed as first treatment in most patients, including asymptomatic cases. The only exception concerns patients with severe symptoms in whom it is recommended to combine zinc with D-penicillamine during the early phase of treatment for more rapid effectiveness. Because of its safety, zinc is particularly indicated in cases of intolerance to D-penicillamine and trien.",adolescent;adult;article;clinical article;controlled study;female;human;male;priority journal;Wilson disease/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Bona, I.;Broussolle, E.;Neuschwander, P.;Confavreux, C.;Fontanges, T.;Accominotti, M.;Chazot, G.",1993,,,0,0,
2638,Zinc in the treatment of Wilson's disease: how it works,,adult;article;biopsy;endoscopy;female;human;intestine;male;metabolism;middle aged;pathology;Wilson disease/dt [Drug Therapy];metallothionein;zinc/dt [Drug Therapy],"Friedman, L. S.;Yarze, J. C.",1993,May,,0,0,
2639,Hepatic Wilson's disease in two brothers,,article;case report;copper metabolism;human;liver biopsy;male;school child;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ching, M. C.;Domingo, E. O.;Ibanez, L. T.",1993,,,0,0,
2640,Mammary hyperplasia secondary to treatment with D-penicillamine in a patient with Wilson's disease. [Spanish],,adolescent;article;breast cancer/si [Side Effect];case report;female;human;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Caballeria, J.;Caballeria, L.;Cabre, J.;Bruguera, M.;Rodes, J.",1993,,,0,0,
2641,Wilson's disease and offending behaviour - A case report,,adult;affective neurosis;article;autosomal recessive disorder/cn [Congenital Disorder];behavior disorder;case report;copper metabolism;criminal behavior;diagnosis;forensic psychiatry;hospitalization;human;intellectual impairment;liver dysfunction;male;medical record;mental disease;neurologic disease;offender;organic brain syndrome;personality disorder;priority journal;psychosexual disorder;sexual crime;social behavior;Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Kaul, A.;McMahon, D.",1993,,,0,0,
2642,Hemolytic episode in a patient with Wilson's disease treated with zinc,,Hemolytic anemia;Wilson's disease;Zinc-sulphate;adult;article;case report;clinical feature;female;hemolytic anemia/dt [Drug Therapy];hemolytic anemia/si [Side Effect];human;priority journal;symptom;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy],"Shimon, I.;Sela, B. A.;Moses, B.;Dolev, E.",1993,,,0,0,
2643,Massive hematuria in children with Wilson disease,,adolescent;clinical article;female;hematuria/dt [Drug Therapy];human;hypophosphatemia;letter;male;school child;Wilson disease;penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Ozsoylu, S.;Kocak, N.;Yuce, A.",1993,,,0,0,
2644,Fatal deterioration of Wilson's disease after institution of oral zinc therapy [2],,adult;case report;copper blood level;diet restriction;esophagus varices bleeding/co [Complication];extrapyramidal syndrome/co [Complication];human;human cell;human tissue;letter;liver failure/si [Side Effect];male;neurotoxicity/si [Side Effect];nuclear magnetic resonance imaging;oral drug administration;parkinsonism/co [Complication];priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];zinc metabolism;cobalt;iron;magnesium;manganese;penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];potassium/cb [Drug Combination];potassium/do [Drug Dose];potassium/dt [Drug Therapy];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/ad [Drug Administration];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy];zinc sulfate/pd [Pharmacology],"Lang, C. J. G.;Rabas-Kolominsky, P.;Engelhardt, A.;Kobras, G.;Konig, H. J.",1993,,,0,0,
2645,A study of trientine therapy in Wilson's disease with neurological symptoms. [Japanese],"D-penicillamine, an orally-administered chelating agents, is effective for Wilson's disease (WD). However 25% of WD patients showed serious adverse reactions to D-penicillamine cause this drug to be discontinued after months or years of treatment. For these cases, trientine-2HCl and trientine-4HCl, less toxic agents, are investigated. Three patients with WD, associated with neurological symptoms, were given either trientine-2HCl or trientine-4HCl. These patients had been on therapy with D-penicillamine. Severe adverse reactions had developed during the course of therapy, and D-penicillamine was discontinued, pancytopenia in case 1, nephrotic syndrome in case 2, and myasthenia gravis in case 3. Trientine-2HCl for case 1, and trientine-4HCl for cases 2 and 3 were instituted and continued. The neurological findings in all patients were extremely improved without side effects by trientine therapy. Though the chelating action on copper is weaker than that of D-penicillamine, it is efficient in improvement of the clinical neurological symptoms.",adolescent;adult;article;case report;controlled study;female;human;male;myasthenia gravis/si [Side Effect];nephrotic syndrome/si [Side Effect];pancytopenia/si [Side Effect];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];diazepam;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Suda, M.;Kubota, J.;Yamaguchi, Y.;Fujioka, Y.;Saito, Y.;Aoki, T.",1993,,,0,0,
2646,"Neurologic complications of inherited mitochondrial abnormality, and neurologic consequences of inborn errors of metabolism","The possibility of gene therapy for patients with Menkes or Gaucher's disease has been improved by the isolation of a promising candidate gene and production of a mouse model, respectively. Many mutations of mitochondrial DNA are being associated with mitochondrial encephalomyopathies, and protection of the resultant biochemical deficiency can be achieved with a remarkably low percentage of normal mitochondrial DNA. The correlation between mutation, biochemical deficiency, and neurologic consequence, however, remains frustratingly obscure. Gas chromatography-mass spectrometric urinalysis is becoming increasingly important in the diagnosis of metabolic disorders and is revealing new and unexpected deficiencies.",amino acid metabolism;animal experiment;animal model;encephalomyopathy/dt [Drug Therapy];encephalomyopathy/et [Etiology];fatty acid metabolism;gas chromatography;Gaucher disease/dt [Drug Therapy];gene isolation;gene mutation;gene therapy;glycogen storage disease/cn [Congenital Disorder];human;inborn error of metabolism/di [Diagnosis];inborn error of metabolism/dt [Drug Therapy];inborn error of metabolism/et [Etiology];mass spectrometry;Menkes syndrome/cn [Congenital Disorder];Menkes syndrome/dt [Drug Therapy];Menkes syndrome/et [Etiology];metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];mitochondrial myopathy/cn [Congenital Disorder];mitochondrial myopathy/di [Diagnosis];mitochondrial myopathy/et [Etiology];mitochondrial myopathy/th [Therapy];neurological complication/et [Etiology];nonhuman;oxidative phosphorylation;review;side effect;urinalysis;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];X chromosome linkage;mitochondrial DNA/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Lightowlers, R. N.",1993,,,0,0,
2647,Treatable diseases of the nervous system with cataract formation. [German],"The detection of a cataract in combination with a neurological deficit may provide the physician with important diagnostic help. But a minority of underlying diseases (angioceratoma corporis diffusum, cerebrotendineous xanthomatosis, diabetes mellitus, galactosemia, hypocalcemia, Refsum's disease, Wilson's disease; Charles Bonnet syndrome; relapsing Perichondritis; adverse effects of medication and intoxications) can be treated causally. Therefore they are summed up and discussed in this paper.",cataract/et [Etiology];cerebrotendinous xanthomatosis;diabetes mellitus;galactosemia/th [Therapy];human;neurologic disease/co [Complication];neurologic disease/dt [Drug Therapy];neurologic disease/si [Side Effect];polychondritis/dt [Drug Therapy];priority journal;review;Wilson disease/dt [Drug Therapy];azathioprine/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];chlorambucil/dt [Drug Therapy];chlorpromazine/ae [Adverse Drug Reaction];colchicine/dt [Drug Therapy];corticosteroid/ae [Adverse Drug Reaction];corticosteroid/dt [Drug Therapy];cyclophosphamide/dt [Drug Therapy];dapsone/dt [Drug Therapy];mercury/to [Drug Toxicity];penicillamine/dt [Drug Therapy],"Baumgartner, R. W.;Waespe, W.",1993,,,0,0,
2648,Alterations in mitochondrial function and morphology in chronic liver disease: Pathogenesis and potential for therapeutic intervention,"Studies assessing mitochondrial function and structure in livers from humans or experimental animals with chronic liver disease, including liver cirrhosis, revealed a variety of alterations in comparison with normal subjects or control animals. Depending on the etiology of chronic liver disease, the function of the electron transport chain and/or ATP synthesis was found to be impaired, leading to decreased oxidative metabolism of various substrates and to impaired recovery of the hepatic energy state after a metabolic insult. Changes in mitochondrial structure include megamitochondria with reduced cristae, dilatation of mitochondrial cristae and crystalloid inclusions in the mitochondrial matrix. The most important strategies to maintain an adequate mitochondrial function per liver are mitochondrial proliferation and increases in the activity of critical enzymes or in the content of cofactors per mitochondrion. Possibilities to assess hepatic mitochondrial function and to treat mitochondrial dysfunction in patients with chronic liver disease are discussed.",alcohol;baboons;copper;fatty liver;hepatocellular carcinoma;humans;iron;liver cirrhosis;metabolism;mitochondria;mitochondrial cytopathies;monkeys;morphology;rats;riboflavin;vitamin B<inf>12</inf>;vitamin D;vitamin E;animal experiment;baboon;biliary cirrhosis;chronic liver disease;human;liver carcinoma;liver function;liver mitochondrion;monkey;nonhuman;priority journal;rat;review;vitamin deficiency;Wilson disease;adenosine;alcohol/to [Drug Toxicity];carbon tetrachloride/to [Drug Toxicity];dimethylnitrosamine/to [Drug Toxicity];flavonoid;misoprostol;penicillamine;thioacetamide/to [Drug Toxicity],"Krahenbuhl, S.",1993,,http://dx.doi.org/10.1016/0163-7258%2893%2990020-E,0,0,
2649,Zinc and red cell fatty acid composition,,acrodermatitis enteropathica/th [Therapy];animal experiment;animal model;arachidonic acid metabolism;diet supplementation;enzyme activity;erythrocyte;letter;lipid composition;nonhuman;phospholipid blood level;priority journal;rat;Wilson disease/th [Therapy];zinc deficiency;arachidonic acid/ec [Endogenous Compound];docosahexaenoic acid/ec [Endogenous Compound];phospholipid/ec [Endogenous Compound];zinc,"Cunnane, S. C.",1993,,,0,0,
2650,Schizophrenia associated with Wilson's disease. [French],"An 18 year-old male first presented a clinical picture of acute psychosis with two reccurences at ages 22 and 23. The diagnosis made at that time was paranoid schizophrenia. Twelve years after his first psychiatric hospitalization, it was discovered that he was suffering from Wilson's disease. In retrospect, the clinical picture was atypical, notably with an important neurologic involvement mainly parkinsonism almost uncontrollable and aggravated with neuroleptics. The chelating treatment with d-penicillamine resulted in partial improvement of the neurological involvement because the extrapyramidal and neurovegetative symptoms persisted. The psychiatric symptoms improved with fewer neuroleptics than during the 12 previous years. However, neuroleptics had to be continued because of the delay in diagnosing the illness, which diminished the efficiency of the single chelating treatment. The clinical presentation and therapeutic response of this patient strongly suggest a link between the cerebral intoxication by copper and the psychiatric symptoms.",adult;article;case report;human;male;oral drug administration;paranoia;parkinsonism;schizophrenia/di [Diagnosis];schizophrenia/dt [Drug Therapy];Wilson disease/di [Diagnosis];copper/to [Drug Toxicity];neuroleptic agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Saint-Laurent, M.",1992,,,0,0,
2651,Wilson's disease with primary CNS manifestation - Current state of diagnosis and therapy. [German],"Five cases studied at our clinic are discussed and the literature reviewed with the aim of assessing the diagnostic value of various examination methods used for Wilson's disease and a modified diagnostic approach is suggested. CT and MRI are compared with regard to sensitivity, specificity and prognostic value. Almost regularly, MRI showed bilateral lesions in the basal ganglia in combination with structural changes in the brain stem. A pattern consisting of symmetrical lesions of the red nuclei, the periaquaductal grey region and, facultatively, the substantia nigra and the dentate nuclei was discovered and appeared almost pathognomonic. Follow-up studies revealed excellent reversibility of MRI changes by both penicillamine and trientine. Auditory evoked potentials showed the highest sensitivity and the best correlation with structural findings. Kayser-Fleischer corneal rings a diagnostic requirement in the literature - were not found in all patients. The current state of therapy and therapy management is discussed on the basis of pathophysiological considerations. As possible complications of penicillamine administration the deterioration of the clinical condition after initiating therapy, and the risks associated with an abrupt termination of therapy are discussed in detail.",adult;basal ganglion;clinical article;evoked auditory response;female;human;male;nuclear magnetic resonance imaging;oral drug administration;priority journal;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Willeit, J.;Kiechl, S. G.;Birbamer, G.;Schmidauer, C.;Felber, S.;Aichner, F.;Saltvari, L.;Metzler, R.;Judmaier, G.",1992,,,0,0,
2652,"Metabolic cirrhoses (haemochromatosis, Wilson's disease, erythropoietic protoporphyria). [French]",,article;erythropoietic protoporphyria;human;liver cirrhosis/dt [Drug Therapy];Wilson disease;penicillamine/dt [Drug Therapy],"Guyader, D.;Jouanolle, H.;Brissot, P.",1991,,,0,0,
2653,Hepatolenticular degeneration: Analysis of neurological manifestations under treatment in 76 patients. [Portuguese],,article;disability;disease severity;female;follow up;human;kidney disease/si [Side Effect];liver disease/co [Complication];major clinical study;male;toxicity/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Barbosa, E. R.;Scaff, M.;Canelas, H. M.",1991,,,0,1,
2654,D-penicillamine-induced IgA deficiency in treatment for Wilson's disease. [German],Serum IgA deficiency was first noted in a 10 year old boy 8 months after the onset of D-penicillamine therapy. Special immunological examinations revealed a deficiency of the secretory component of IgA while cellular functions of T- and B-lymphocytes were normal. The patient showed discrete clinical signs compatible with IgA deficiency. Regular control of patients with Morbus Wilson and D-penicillamine treatment should include measurement of serum immunoglobulin levels.,article;case report;human;immunoglobulin A deficiency/si [Side Effect];immunoglobulin blood level;male;priority journal;school child;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Ibel, H.;Feist, D.;Endres, W.;Belohradsky, B. H.",1990,,,0,0,
2655,Clinical correlations and some peculiarities of the lymphocyte binding sites in the hepatocerebral dystrophy (HCD). [Russian],,article;B lymphocyte;clinical article;human;liver failure;T lymphocyte;Wilson disease;immunoglobulin;penicillamine;spiperone;theophylline,"Gannushkina, I. V.;Zhirnova, I. G.;Chlonkovska, A.;Markova, E. D.;Ivanova-Smolenskaya, I. A.;Poleshchuk, V. V.;Komelkova, L. V.;Katosova, R. K.",1990,,,0,0,
2656,Trunkal myoclonous with spontaneous priapism and seminal ejaculation in Wilson's disease,,adult;case report;ejaculation;heredity;human;letter;male;myoclonus;priapism;priority journal;trunk;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Nair, K. R.;Pillai, P. G.",1990,,,0,0,
2657,Copper in the stools - A marker of the effectiveness of treatment of Wilson's disease with zinc. [German],,article;human;human cell;oral drug administration;Wilson disease;copper;zinc sulfate/dt [Drug Therapy],"Dastych, M.",1990,,,0,0,
2658,Wilson disease. Diagnosis and management difficulties in our country. [Spanish],,acute hepatitis;adult;article;clinical article;female;hemolytic anemia;human;male;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Sempere, E.;Perez-Aguilar, F.;Burguera, J. A.;Berenguer, J.",1989,,,0,0,
2659,Trace element analysis of brain and liver tissues in Wilson-Konovalov's disease. [Russian],,adult;autopsy;brain cortex;case report;extrapyramidal syndrome;histochemistry;histology;human;liver;Wilson disease;copper;lead;magnesium;zinc,"Mzhelskaya, T. I.;Larsky, E. G.;Pashchenko, L. A.;Gladkikh, S. P.;Ivanova-Smolenskaya, I. A.;Markova, E. D.",1989,,,0,0,
2660,Atypical MR presentation of Wilson disease: A possible consequence of paramagnetic effect of copper?,A 53-year-old patient with Wilsons's disease and without autonomic dysfunction presented on T2-weighted MR study an atypical decreased signal intensity of the putamina and the caudate nuclei. Possible explanations of such a signal abnormalities are discussed.,MR study;Wilson disease;adult;article;autosomal recessive disorder/di [Diagnosis];case report;caudate nucleus;electron spin resonance;female;human;nuclear magnetic resonance imaging;priority journal;putamen;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Brugieres, P.;Combes, C.;Ricolfi, F.;Degos, J. D.;Poirier, J.;Gaston, A.",1992,,http://dx.doi.org/10.1007/BF00596341,0,0,
2661,Hepatocellular carcinoma in a case of Wilson's disease,"Hepatocellular carcinoma has rarely been reported in Wilson's disease, particularly in women. We describe the case of a female patient who was diagnosed with Wilson's disease at the age of 39 years, after presenting with severe neurological symptoms. She had significant neurological improvement following penicillamine therapy and succumbed to hepatocellular carcinoma at the age of 72 years, following 33 years of penicillamine therapy. The patient described here was the oldest and only the third female patient with hepatocellular carcinoma complicating Wilson's disease to be reported in the literature.",adult;article;case report;female;histology;human;liver biopsy;liver cancer/et [Etiology];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];dimercaprol/cb [Drug Combination];dimercaprol/dt [Drug Therapy];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy],"Cheng, W. S. C.;Govindarajan, S.;Redeker, A. G.",1992,,,0,0,
2662,Plasma exchange for fulminant Wilson disease [1],,adolescent;case report;drug effect;drug efficacy;female;human;letter;neutropenia/dt [Drug Therapy];neutropenia/si [Side Effect];plasmapheresis;priority journal;prognosis;thrombocytopenia/dt [Drug Therapy];thrombocytopenia/si [Side Effect];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];triethylene tetramine hydrochloride/dt [Drug Therapy];unclassified drug,"Sarles, J.;Lefevre, P.;Picon, G.",1992,,,0,0,
2663,Oral zinc therapy in hepatolenticular degeneration: Three case reports. [Portuguese],,adult;article;case report;drug efficacy;female;human;kidney failure/si [Side Effect];male;nephrotoxicity/si [Side Effect];oral drug administration;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Barbosa, E. R.;De Almeida Burdmann, E.;Cancado, E. R.;Haddad, M. S.;Scaff, M.;Canelas, H. M.",1992,,,0,0,
2664,Thiomolybdates in the treatment of Wilson's disease [1],,human;letter;pancytopenia/si [Side Effect];priority journal;Wilson disease/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/dt [Drug Therapy];thiomolybdic acid/ae [Adverse Drug Reaction];thiomolybdic acid/dt [Drug Therapy],"Walshe, J. M.;Brewer, G. J.",1992,,,0,0,
2665,Disappearance of Kayser-Fleischer rings following liver transplantation,1. Four cases of Kayser-Fleischer rings of Wilson's disease were observed to disappear after liver transplantation. 2. The disappearance of Kayser- Fleischer rings was in reverse order from that in which they appear. 3. The duration of disappearance was variable. 4. The density of Kayser-Fleischer rings correlated with the duration of clinical symptoms.,adult;chelation;clinical article;conference paper;cornea disease/co [Complication];cornea disease/di [Diagnosis];cornea disease/et [Etiology];disease classification;female;follow up;human;liver cirrhosis/co [Complication];liver cirrhosis/su [Surgery];liver transplantation;male;neurologic disease/co [Complication];priority journal;Wilson disease/di [Diagnosis];copper;penicillamine;sulfur,"Song, H. S.;Ku, W. C.;Chen, C. L.",1992,,,0,0,
2666,"Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis","In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu concentration increased in 7 regions, in particular, significantly so in the striatum, hypothalamus, cerebellum, midbrain and cortex. Changes of Zn concentration were not found in any region. The Fe concentration increased in cortex and olfactory lobes. The three LEC groups showed a very high concentration of hepatic Cu and a low concentration of serum Cu compared to LEA rats. In LEC rats aged 32 weeks, however, hepatic Cu decreased and serum Cu increased compared to the other two LEC groups. These results suggest that the increase of the cerebral Cu concentration is closely related to the inherently abnormal Cu metabolism and then to the changes of Cu metabolism from about 13 weeks after birth.",Brain;Copper;Iron;Long-Evans Cinnamon rats;Wilson's disease;Zinc;animal tissue;article;atomic absorption spectrometry;brain region;controlled study;male;mutant;nonhuman;priority journal;rat;Wilson disease;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Sugawara, N.;Ikeda, T.;Sugawara, C.;Kohgo, Y.;Kato, J.;Takeichi, N.",1992,,http://dx.doi.org/10.1016/0006-8993%2892%2991587-5,0,0,
2667,Screening for Wilson's disease in the investigation of hematuria,,Hematuria;Screening;Wilson's disease;adolescent;article;case report;hematuria/et [Etiology];human;kidney tubule disorder/et [Etiology];male;preschool child;priority journal;school child;screening test;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Laufer, J.;Lotan, D.;Passwell, J.;Boichis, H.",1992,,,0,0,
2668,Clinical study of Wilson's disease in Taiwan,"From 1968 to 1989, 34 patients with Wilson's disease were diagnosed in the Veterans General Hospital-Taipei. The average age of onset of symptoms and signs was 18.1 years. The Kayser-Pleischer ring was the most common sign (97.1%), followed by tremor (76.5%) and rigidity (41.2%). Biochemically, serum copper and ceruloplasmin level decreased, and 24-hour urinary copper excretion increased in all patients. Interestingly, 19 patients were negative for hepatitis B surface antigen, in contrast to its high prevalence (15%) among the general population in Taiwan. Six patients received liver biopsy to show liver cirrhosis in 2 patients and chronic active hepatitis in the remaining four. Atomic absorption was used for copper quantitative test in 2 patients to show abnormally high copper content in the liver tissue of both. All patients received D-penicillamine treatment with improved neurologic symptoms, and one patient was shifted to zinc sulphate due to bone marrow suppression. By the end of 1989, 5 patients had died of hepatic failure - one of them died 12 days after liver transplantation due to primary graft failure and sepsis, and two died of neurologic complications. This study showed that the clinical manifestations and laboratory findings of our patients were similar to those of Western reports, except that most of our patients with an early onset developed mixed syndrome instead of hepatic symptoms only.",adult;article;clinical article;female;human;male;school child;Taiwan;Wilson disease/cn [Congenital Disorder];Wilson disease/ep [Epidemiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound],"Chang, C. F.;Shen, M. T.;Wu, J. C.;Hwang, S. J.;Lo, G. H.;Lai, K. H.;Lee, S. D.",1992,,,0,0,
2669,Fulminant hepatic failure and acute intravascular haemolysis as presenting manifestations of Wilson's disease in young children,"The cases of three young children (mean age 5.8 years) in whom fulminant hepatic failure and acute intravascular haemolysis were the presenting manifestations of Wilson's disease are reported. Although diagnosis was made ante-mortem and chelation therapy instituted, the course was relentlessly fatal in all three cases. This presentation of Wilson's disease at such a young age is noteworthy.",article;case report;female;human;human tissue;intravascular hemolysis;intravenous drug administration;liver cirrhosis/dt [Drug Therapy];liver failure/dt [Drug Therapy];male;oral drug administration;preschool child;school child;Wilson disease/dt [Drug Therapy];ampicillin/dt [Drug Therapy];cimetidine/dt [Drug Therapy];lactisyn/dt [Drug Therapy];penicillamine/dt [Drug Therapy];unclassified drug,"Walia, B. N. S.;Singh, S.;Marwaha, R. K.;Bhusnurmath, S. R.;Dilawari, J. B.",1992,,,0,0,
2670,Chronic liver disease: The scope of causes and treatments,"Evaluation of chronic liver disease begins with a carefully taken history, thorough physical examination, and standard laboratory tests. Often, however, other studies are required, such as a viral hepatitis panel, serologic tests for autoimmune markers, tests for antimitochondrial antibodies, measurement of serum iron and ceruloplasmin levels, liver biopsy, and imaging studies of the extrahepatic bile ducts. Medical treatment of chronic active hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis remains unsatisfactory. Early treatment of hemochromatosis and Wilson's disease can prevent cirrhosis and liver failure. Liver transplantation is now a viable procedure for patients with end-stage chronic liver disease.",alcohol liver disease/di [Diagnosis];alpha 1 antitrypsin deficiency/cn [Congenital Disorder];alpha 1 antitrypsin deficiency/di [Diagnosis];autoimmune hepatitis/di [Diagnosis];autoimmune hepatitis/dt [Drug Therapy];chronic liver disease/di [Diagnosis];chronic liver disease/dt [Drug Therapy];chronic liver disease/et [Etiology];hemochromatosis/cn [Congenital Disorder];hemochromatosis/di [Diagnosis];hemochromatosis/dt [Drug Therapy];hemochromatosis/th [Therapy];hepatitis B/di [Diagnosis];hepatitis B/dt [Drug Therapy];hepatitis C/di [Diagnosis];hepatitis C/dt [Drug Therapy];human;intravenous drug administration;liver biopsy;liver cell carcinoma/co [Complication];liver cell carcinoma/di [Diagnosis];liver cirrhosis/co [Complication];liver failure/co [Complication];liver function test;liver toxicity/si [Side Effect];liver transplantation;oral drug administration;primary biliary cirrhosis/di [Diagnosis];primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/di [Diagnosis];primary sclerosing cholangitis/dt [Drug Therapy];priority journal;review;virus hepatitis/di [Diagnosis];virus hepatitis/dt [Drug Therapy];virus hepatitis/et [Etiology];Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alpha2b interferon/dt [Drug Therapy];analgesic agent/ae [Adverse Drug Reaction];androgen/ae [Adverse Drug Reaction];azathioprine/dt [Drug Therapy];chlorambucil/dt [Drug Therapy];colchicine/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];cyclosporin A;isoniazid/ae [Adverse Drug Reaction];methotrexate/ae [Adverse Drug Reaction];methyldopa/ae [Adverse Drug Reaction];nicotinic acid/ae [Adverse Drug Reaction];nitrofurantoin/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];trientine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy],"Babb, R. R.",1992,,,0,0,
2671,Diagnosing Wilson disease [4],,ceruloplasmin blood level;differential diagnosis;letter;liver failure/di [Diagnosis];liver function;priority journal;Wilson disease/di [Diagnosis];copper 64;penicillamine,"Yarze, J. C.;Munoz, S. J.;Friedman, L. S.;Stremmel, W.;Sowa, J. M.",1992,,,0,0,
2672,Detailed evaluation of evoked potentials in Wilson's disease,"Detailed evoked potentials (EPs) were studied in 52 patients (28.7 +/- 11.9 years) with Wilson's disease (WD). Various peak latencies, interpeak latencies and amplitudes of somatosensory, auditory brain-stem and visual EPs were significantly abnormal in the group of 28 neurologically symptomatic patients as compared to controls. Interhemisphere latency and amplitude differences tended to be increased without reaching significance, indicating a symmetrical rather than focal subclinical brain involvement. Selected conduction times of at least 1 EP modality were prolonged in all 4 patients with severe, in 16 of 18 with moderate, in 4 of 6 with mild, and in 4 of 24 patients without neurological symptoms. Auditory brain-stem and somatosensory EPs were more frequently prolonged than visual EPs (more abnormalities with check sizes of 13 than 54 min of arc). Cortical somatosensory EPs correlated well (P << 0.01) with either Fz or earlobe reference.",Brain dysfunction;Evoked potentials;Wilson's disease;adolescent;adult;article;chorea;dysarthria;dystonia;evoked auditory response;evoked response;evoked somatosensory response;evoked visual response;female;human;major clinical study;male;priority journal;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Grimm, G.;Madl, C.;Katzenschlager, R.;Oder, W.;Ferenci, P.;Gangl, A.",1992,,,0,0,
2673,Penicillamine-induced pseudoxanthoma elasticum-like skin changes requiring rhytidectomy,"A 42-year-old woman with pronounced skin laxity of her neck underwent a rhytidectomy and was found to have pseudoxanthoma elasticum-like changes of her skin. Her medical history was significant for Wilson's disease, requiring that she take penicillamine for 26 years. In patients on long-term penicillamine therapy, 20% to 33% will develop a dermatopathy. The drug has been used to alter scar formation in various surgical conditions. Penicillamine is known to alter cross-linking of elastin and collagen fibers. A review of the literature reveals other penicillamine-related dermatopathies that may present to the surgeon.",adult;article;case report;cross linking;cutis laxa/si [Side Effect];drug induced disease/si [Side Effect];drug induced disease/su [Surgery];drug mechanism;female;histopathology;human;pemphigus/si [Side Effect];pseudoxanthoma elasticum;rhytidoplasty;skin atrophy/si [Side Effect];skin biopsy;skin disease/si [Side Effect];skin disease/su [Surgery];Wilson disease/dt [Drug Therapy];collagen/ec [Endogenous Compound];elastin/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology],"Narron, G. H.;Zec, N.;Neves, R. I.;Manders, E. K.;Sexton Jr, F. M.",1992,,,0,0,
2674,A case of penicillamine dermatopathy. [Japanese],,D-penicillamine;penicillamine dermatopathy;Wilson's disease;article;case report;histology;human;skin defect/si [Side Effect];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Abumi, J.;Azuma, T.;Naito, Y.;Tomita, S.;Komamura, H.;Yoshikawa, K.",1992,,,0,0,
2675,An autopsy case of Wilson's disease complicating fatal acute liver failure and hemolytic anemia after discontinuation of therapy. [Japanese],,adolescent;article;autopsy;case report;female;hemolytic anemia/co [Complication];hemolytic anemia/et [Etiology];histology;human;liver failure/co [Complication];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Asahina, Y.;Sakamoto, N.;Kamiyama, T.;Tazawa, J.;Nishimura, M.;Sato, C.;Marumo, F.",1992,,,0,0,
2676,Drug therapy for hepatic fibrosis,"Cirrhosis is a disease that is characterized by widespread deposition of connective tissue throughout the hepatic parenchyma. The disease can lead to major clinical consequences including portal hypertension and hepatic failure. Development of specific antifibrotic therapy has been problematic; current approaches to therapy are often diverse. Some forms of fibrogenic liver disease are clearly attributable to either an infectious agent or a hepatotoxin. In these cases, agents such as praziquantel, deferoxamine, and penicillamine, can be used to prevent or retard the development of cirrhosis. For other liver diseases, specific treatments are available, but their effects on cirrhosis are unproven. Only corticosteroids, D-penicillamine, colchicine, and malotilate have been evaluated in humans-all provide limited success. Further testing of these agents, as well as gamma-interferon and other immunosuppressive agents, should provide further information regarding their safety and efficacy.","alcoholism;animal experiment;animal model;controlled study;hemochromatosis/dt [Drug Therapy];hemochromatosis/th [Therapy];hepatitis B/dt [Drug Therapy];hepatitis C/dt [Drug Therapy];human;liver cirrhosis/et [Etiology];liver fibrosis/co [Complication];liver fibrosis/dt [Drug Therapy];liver fibrosis/et [Etiology];liver fibrosis/pc [Prevention];major clinical study;mouse;nonhuman;oral drug administration;review;schistosomiasis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];16,16 dimethylprostaglandin E2/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];colchicine/dt [Drug Therapy];collagen/ec [Endogenous Compound];corticosteroid/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];deferoxamine mesylate;dexamethasone/dt [Drug Therapy];dexamethasone/pd [Pharmacology];gamma interferon/dt [Drug Therapy];malotilate/dt [Drug Therapy];methylprednisolone/dt [Drug Therapy];methylprednisolone/pd [Pharmacology];penicillamine/dt [Drug Therapy];praziquantel/dt [Drug Therapy];prednisone/dt [Drug Therapy];proline derivative/dt [Drug Therapy];prostaglandin derivative/dt [Drug Therapy];retinoid/dt [Drug Therapy]","Maher, J. J.",1992,,,0,0,
2677,Jaundice,"Jaundice is a disorder of bilirubin metabolism and has many causes. History and physical examination help establish the diagnosis in 70 to 80 percent of patients. Elevation of alkaline phosphatase and gamma-glutamyl transpeptidase suggests cholestasis, either intrahepatic (e.g., medication reactions) or extrahepatic (e.g., choledocholithiasis), whereas markedly elevated serum aminotransferases are indicative of hepatocellular damage from infection, toxins or ischemia. Ultrasound examination is a useful initial procedure when extrahepatic obstruction is suspected. Endoscopic retrograde cholangiopancreatography and computed tomography may be better used to diagnose obstruction at the level of the pancreas or distal common bile duct. The treatment is based on the etiology of jaundice and includes removal of offending medications or toxins, therapy for underlying liver disease or surgery for extrahepatic obstruction.",aminotransferase blood level;autoimmune hepatitis/dt [Drug Therapy];computer assisted tomography;drug induced disease;echography;endoscopic retrograde cholangiopancreatography;extrahepatic bile duct obstruction/di [Diagnosis];extrahepatic bile duct obstruction/su [Surgery];hepatobiliary scintiscanning;human;hyperbilirubinemia/et [Etiology];intrahepatic cholestasis/di [Diagnosis];intrahepatic cholestasis/dt [Drug Therapy];jaundice/di [Diagnosis];jaundice/ep [Epidemiology];jaundice/et [Etiology];liver cell damage/di [Diagnosis];priority journal;review;virus hepatitis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];alkaline phosphatase/ec [Endogenous Compound];antihypertensive agent;antiinfective agent;antineoplastic agent;corticosteroid/dt [Drug Therapy];diuretic agent;gamma glutamyltransferase/ec [Endogenous Compound];hypnotic sedative agent;inhalation anesthetic agent;interferon/dt [Drug Therapy];nonsteroid antiinflammatory agent;penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy],"McKnight, J. T.;Jones, J. E.",1992,,,0,0,
2678,"Metallothionein concentration in the liver of patients with Wilson's disease, primary biliary cirrhosis, and liver metastasis of colorectal cancer","In patients with primary biliary cirrhosis and Wilson's disease liver copper concentrations become elevated during the evolution of the disorder. The accumulated copper is thought to be detoxified by metallothionein, a protein which binds copper and zinc. In liver metastasis of colorectal cancer, copper and zinc concentrations are usually decreased compared to normal liver tissue, but little is known about the concomitant metallothionein levels. In the present study metallothionein concentrations were determined in archival liver samples from patients with primary biliary cirrhosis and Wilson's disease, and in both normal and malignancy-containing liver samples from patients with metastasis from a colorectal adenocarcinoma. Twenty-seven control liver samples contained 3.98 +/- 1.55 mg metallothionein/g protein. From the 21 liver samples of patients with primary biliary cirrhosis, which had a mean metallothionein concentration of 6.06 +/- 5.03 mg/g protein, 6 were above the highest control level. Liver metallothionein concentrations for the 8 patients with Wilson's disease were significantly elevated (10.98 +/- 6.93 mg/g protein, P < 0.005 vs. controls and p < 0.05 vs. primary biliary cirrhosis). In the 11 liver metastases from colorectal adenocarcinomas metallothionein concentrations (1.17 +/- 0.90 mg/g protein) were significantly (p < 0.005) lower than surrounding normal liver tissue (4.25 +/- 1.75 mg/g protein). We conclude that in primary biliary cirrhosis and Wilson's disease increased liver metallothionein concentrations may detoxify the accumulated copper. Furthermore, liver metastasis of colorectal cancer contains less metallothionein than the surrounding normal liver tissue.",adenocarcinoma;copper;radioimmunoassay;adult;aged;article;autopsy;clinical article;colorectal cancer;controlled study;female;human;human tissue;liver metastasis;male;oral drug administration;primary biliary cirrhosis;priority journal;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/do [Drug Dose];zinc/dt [Drug Therapy],"Mulder, T. P. J.;Janssens, A. R.;Verspaget, H. W.;Van Hattum, J.;Lamers, C. B. H. W.",1992,,http://dx.doi.org/10.1016/S0168-8278%2805%2980667-1,0,0,
2679,The hepatic form of Wilson's disease. Seven-year treatment follow-up of 7 familial cases. [French],The authors report seven familial cases of hepatic forms of Wilson's disease. Therapy was Triene (1 case) and D Penicillamine (6 cases). The iatrogenic effects of treatment were not observed. One pregnancy and one liver transplantation has successful outcomes.,adolescent;adult;child;clinical article;conference paper;controlled study;copper metabolism;follow up;genetic disorder/dt [Drug Therapy];human;liver disease;priority journal;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Valmary, J.;Algayres, J. P.;Thiolet, C.;Coutant, G.;Bili, H.;Daly, J. P.",1992,,http://dx.doi.org/10.1016/S0248-8663%2805%2980984-1,0,1,
2680,Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson's disease,"To investigate the diagnostic value of 24-hr urinary copper excretion testing after penicillamine challenge in the diagnosis of Wilson's disease, 75 consecutive children referred for a variety of liver problems and in whom parameters of copper metabolism had been investigated were analyzed retrospectively. Seventeen had Wilson's disease, 22 had autoimmune chronic active hepatitis, 6 had primary sclerosing cholangitis, 12 had chronic liver disease of various etiologies, 4 had cryptogenic acute liver failure, 6 had acute hepatitic illnesses and 8 had a variety of disorders featuring normal liver histological appearance. Serum ceruloplasmin and total copper levels were significantly lower in Wilson's disease patients compared with all other groups, but three children with Wilson's disease had normal ceruloplasmin levels and seven had normal total copper levels. No significant difference was found for free serum copper levels and liver copper content between Wilson's disease patients and the other groups. Baseline 24-hr urinary copper excretion was significantly higher in Wilson's disease patients compared with that of the other patients, but six children with Wilson's disease had levels just above the upper limit of normal, overlapping with values obtained in three children with liver failure, two with acute hepatitis, two with autoimmune chronic active hepatitis and three with primary sclerosing cholangitis. The 24-hr urinary copper excretion after penicillamine challenge proved the most accurate single diagnostic test; levels more than 25 mumol/24 hr were present in 15 of 17 patients with Wilson's disease, but in only 1 child with liver failure of the 58 with other disorders. The penicillamine challenge is a valuable aid in the diagnosis of Wilson's disease, particularly in children with no Kaiser-Fleischer rings.",adolescent;adult;article;ceruloplasmin blood level;child;copper blood level;copper metabolism;diagnostic accuracy;diagnostic value;human;major clinical study;priority journal;urinary excretion;urine level;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine,"Da Costa, C. M.;Baldwin, D.;Portmann, B.;Lolin, Y.;Mowat, A. P.;Mieli-Vergani, G.",1992,,,0,0,
2681,"Copper metabolism in hypercupremic human livers. Studies of its subcellular distribution, association with binding proteins and expression of mRNAs","In the present study we have used differential centrifugation, size exclusion chromatography, Western and Northern blotting to investigate the subcellular distribution of hepatic copper, the association of the metal with hepatic copper binding proteins and the expression of specific mRNAs for copper binding proteins in liver tissue from two patients with Wilson's disease, two patients with chronic liver disease and two patients with normal hepatic copper levels. Unlike previous studies the present results fail to show any gross differences in subcellular distribution of copper between the livers, with most of the copper being found in the soluble supernatant where it is associated with metallothionein. Caeruloplasmin mRNA levels were reduced in the two patients with Wilson's disease and also in a patient with fulminant hepatic failure. It remains to be confirmed if the reduction of caeruloplasmin mRNA is specific for Wilson's disease. Levels of mRNAs for copper zinc superoxide dismutase and metallothionein were variable and not related to liver copper.",article;ceruloplasmin blood level;copper metabolism;human;human tissue;liver failure/et [Etiology];liver toxicity;priority journal;Wilson disease;copper/ec [Endogenous Compound],"Bingle, C. D.;Srai, S. K. S.;Epstein, O.",1992,,http://dx.doi.org/10.1016/0168-8278%2892%2990018-K,0,0,
2682,Wilson's disease. [Spanish],,human;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Borda, F.;Fortun, M. T.;Vidan, J. R.;Guerra, A.",1992,,,0,0,
2683,Wilson's disease. [Italian],,adverse drug reaction;clinical feature;drug choice;drug contraindication;human;nephrotoxicity/si [Side Effect];neurotoxicity/si [Side Effect];pathogenesis;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];sufortan;tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Cramarossa, L.;D'Angelo, D.;D'Ascanio, I.;Ferri, G. B.;Piane, E.",1992,,,0,0,
2684,Treatment of Wilson's disease: Penicillamine or triene?,,human;letter;nuclear magnetic resonance imaging;priority journal;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc,"Kiechl, S. G.;Willeit, J.;Aichner, F.;Felber, S.;Siegemund, R.",1992,,,0,0,
2685,Triethylenetetramine therapy for D-penicillamine-intolerant patients with Wilson's disease: Preclinical and clinical studies on the safety and efficacy of triethylenetetramine,,adult;animal experiment;animal model;article;chelation;child;clinical article;copper blood level;drug efficacy;drug safety;female;human;lethal dose;male;nonhuman;oral drug administration;rat;toxicity testing;Wilson disease/dt [Drug Therapy];penicillamine/ct [Clinical Trial];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];trientine/ct [Clinical Trial];trientine/dt [Drug Therapy];trientine/to [Drug Toxicity],"Yamaguchi, Y.",1992,,,0,0,
2686,Wilson's disease and pregnancy. [Croatian],"Wilson's disease is rare autosomal-recessive disorder originated on the basis of metabolic copper over-storage. This is the case report of patient aged 28, who suffers Wilson's disease during last ten years. She has been treated by penicillamine unregularly from the beginning of her disease. She reported three spontaneous abortions in her previous history. She was treated by penicillamin and bedoxin in current pregnancy. Vaginal delivery was completed using oxytocin stimulation. Newborn was male, alive, with body weight of 2900 grams. Apgar score was 8. During puerperal period normal uterine involution was estimated, but lactation was ceased.",adult;article;case report;female;human;male;newborn;pregnancy;pregnancy complication/th [Therapy];Wilson disease/th [Therapy],"Avramovic, D.;Gligorovic, S.;Jovanovic-Tajfl, S.;Kastratovic, B.",1992,1992,,0,0,
2687,Diagnostic difficulties and therapeutic success in Wilson-Konovalov disease. [Russian],,adolescent;article;biopsy;case report;differential diagnosis;drug combination;female;genetics;hepatomegaly/di [Diagnosis];hepatomegaly/dt [Drug Therapy];human;liver;pathology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ad [Drug Administration];prednisolone/ad [Drug Administration],"Prokhorova, M. V.;Krel, P. E.",1992,,,0,0,
2688,Results of the treatment of Wilson's disease with zinc sulfate and d-penicillamine. [Polish],"Nine patients with newly diagnosed Wilson's disease were treated with zinc sulphate for 12 months. Polish preparation Zincteral was administered in doses of 200 mg 4 times daily. The neurological status has improved in five cases. No adverse reactions of zinc sulphate were observed. The results were compared with the therapeutic effect, obtained in the group of 10 patients who received d-penicillamine (Cuprenil-Polfa) 1.0-1.5 g daily from the very beginning. In three cases drug was discontinued due to adverse reactions. In remaining seven cases, in five evidence of the clinical improvement of the neurological status was observed, but in one case during 12 months of observation progressing deterioration was noticed. Neurological state of one patient remained unchanged.",adult;article;clinical trial;comparative study;controlled study;drug administration;female;human;male;remission;time;Wilson disease/dt [Drug Therapy];penicillamine/ad [Drug Administration];sulfate/ad [Drug Administration];zinc/ad [Drug Administration];zinc sulfate,"Szleper, M.;Rodo, M.;Pilkowska, E.;Czlonkowska, A.",1992,1992 May,,0,0,
2689,D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper metabolism,"The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D-penicillamine. D-Penicillamine is a copper-chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D-penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long-Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D-penicillamine-treated Long-Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in the liver.",animal experiment;article;copper metabolism;hepatitis/co [Complication];hepatitis/et [Etiology];hepatitis/pc [Prevention];histology;liver;nonhuman;oral drug administration;priority journal;rat;Wilson disease;copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];steroid/pd [Pharmacology],"Togashi, Y.;Li, Y.;Kang, J. H.;Takeichi, N.;Fujioka, Y.;Nagashima, K.;Kobayashi, H.",1992,,,0,0,
2690,Wilson's disease and pregnancy. [Slovak],"The authors describe the case of a 27-year-old female patient with Wilson's disease who during penicillinamine treatment became pregnant and was delivered of a healthy infant. The diagnosis of Wilson's disease was confirmed by the finding of a Kayser-Fleischer ring in the cornea and a concurrent serum ceruloplasmin concentration lower than 0.20 g/l. Unrecognized and untreated, the disease is associated with the development of organ complications which in the end prove fatal. On the other hand, early diagnosis and effective treatment throughout life can prevent liver and brain damage and thus enable the patient to live a normal life and women can have a healthy child.",adult;article;case report;female;human;pregnancy;pregnancy complication/th [Therapy];Wilson disease/th [Therapy],"Stvrtinova, V.;Balazovjech, I.;Hlinstakova, S.;Hlinstak, K.;Sasko, A.",1992,Mar,,0,0,
2691,Wilson's disease. A retrospective analysis of 12 cases. [Spanish],"We reviewed retrospectively 12 patients with Wilson's disease diagnosed during a 16-year period (1974-1989). The prevalence rate was 0.6 per 100,000 individuals. Clinical onset was hepatic (50%) or neurologic (50%), but at diagnosis (6.4 years later) 67% of patients showed several clinical manifestations: hepatic, neurologic, renal and haematologic. Among the essential diagnostic indices we find false negative results for Kayser-Fleischer ring (25%), serum ceruloplasmin (8%) and total serum copper (34%). Ten patients were treated with penicillamine. This drug was effective and well tolerated, although one patient (10%) developed membranous nephritis and required to change successively to BAL and trien. In a 61 months follow-up 5 patients (42%) died from severe liver failure. Patients with poor prognosis had a diagnostic delay and a liver failure degree significantly greater than patients with good prognosis. Our results suggest the following conclusions: a) in Spain the prevalence rate of Wilson's disease is near the lower reported rate; b) the early diagnosis of Wilson's disease is rare; c) diagnosis should be made only when several essential indices are positive; d) early hepatic transplantation showed carried out in patients with acute or chronic severe liver failure.",age;article;follow up;human;mortality;prognosis;retrospective study;sex difference;Spain/ep [Epidemiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];ceruloplasmin/an [Drug Analysis];copper/an [Drug Analysis];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration],"Castellano, G.;Blasco, A.;Ballesta, F.;Colina, F.;Moreno, D.;Franch, O.;Urruzuno, P.;Solis, J. A.",1992,Mar,,0,0,
2692,Failure of simple biochemical indexes to reliably differentiate fulminant Wilson's disease from other causes of fulminant liver failure,"Serum, urine and tissue biochemical findings were studied in 21 cases of fulminant Wilson's disease with respect to the value of a recently described biochemical index based on serum alkaline phosphatase and total serum bilirubin levels, and these cases were compared with 193 other cases of fulminant liver failure. Serum bilirubin, alkaline phosphatase and AST levels found in fulminant Wilson's disease were significantly different from those found in other cases of fulminant liver failure, but differentiation from other causes of fulminant liver failure on the basis of these biochemical parameters was not possible. The alkaline phosphatase/bilirubin and aspartate AST/bilirubin ratios derived from the above parameters were also significantly lower in fulminant Wilson's disease than in other categories of fulminant liver failure, but distinction between diagnostic categories on this basis was not possible. When ratios that correctly identified all cases of fulminant Wilson's disease were selected, 59/190 (31%) and 84/190 (44%) cases of non-Wilsonian fulminant liver failure would erroneously be assigned a diagnosis of fulminant Wilson's disease, by alkaline phosphatase/bilirubin and AST/bilirubin ratios, respectively. A low alkaline phosphatase-to- bilirubin ratio (<0.57) in any category of fulminant liver failure suggested a significantly worse prognosis than in cases with higher ratios (chi<sup>2</sup>, Yates' corrected = 5.37, p = 0.02). In the Wilson's disease group, serum and hepatic copper and ceruloplasmin concentrations were normal in 4/21, 2/15 and 2/19, respectively, whereas urinary copper level was elevated in 18/18 and was the most valuable test in diagnosis. Massively elevated hepatic copper stores with normal serum copper concentrations were seen in some patients; in others tissue copper concentration from different regions of the same liver varied up to 7-fold. Treatment with D-penicillamine in five patients had no observable beneficial effect.",adolescent;adult;alkaline phosphatase blood level;article;aspartate aminotransferase blood level;bilirubin blood level;child;clinical article;female;human;human tissue;liver failure/di [Diagnosis];liver failure/et [Etiology];male;priority journal;prognosis;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alkaline phosphatase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Sallie, R.;Katsiyiannakis, L.;Baldwin, D.;Davies, S.;O'Grady, J.;Mowat, A.;Mieli-Vergani, G.;Williams, R.",1992,,http://dx.doi.org/10.1016/0270-9139%2892%2990016-3,0,0,
2693,Comparison of disposition behavior and de-coppering effect of triethylenetetramine in animal model for Wilson's disease (Long-Evans Cinnamon rat) with normal Wistar rat,"The disposition behaviors and de-coppering effect of triethylenetetramine dihydrochloride (trientine), a selective chelating agent for copper and an 'orphan drug' for Wilson's disease, have been evaluated in an animal model, Long-Evans Cinnamon (LEC) rats, and normal rats (Wistar). In LEC rats, urinary excretion of trientine was remarkably lower than that of Wistar rats. The absorption rates from the jejunal loop and in vitro metabolism in the liver S9 fraction (supernatant of 9000 x g) were approximately the same for both strains. The decline of urinary excretion of trientine in LEC rats is thought to be due mainly to the lowering of the functional activity of the kidney, because urinary excretion of creatinine and phenolsulfonphthalein were significantly lower in LEC rats than those in Wistar rats. Both acceleration of urinary excretion of copper and reduction of hepatic copper levels were observed with treatment of trientine in LEC rats aged 6 weeks. In LEC rats aged 13 weeks, however, no de-coppering effect from the liver was observed, though urinary excretion of copper was increased. These results suggest that trientine has a pharmacological effect in disease, especially in the early stages of hepatitis.",animal experiment;animal model;animal tissue;article;controlled study;drug absorption;drug metabolism;drug urine level;intragastric drug administration;kidney function;liver;male;nonhuman;rat;Wilson disease/dt [Drug Therapy];chelating agent/cr [Drug Concentration];chelating agent/dt [Drug Therapy];chelating agent/pk [Pharmacokinetics];chelating agent/pd [Pharmacology];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];trientine/cr [Drug Concentration];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics];trientine/pd [Pharmacology],"Iseki, K.;Kobayashi, M.;Ohba, A.;Miyazaki, K.;Li, Y.;Togashi, Y.;Takeichi, N.",1992,,http://dx.doi.org/10.1002/bdd.2510130406,0,0,
2694,Liver and biliary tract diseases: Advances in 1990. [German],,bile duct disease/dt [Drug Therapy];cholelithiasis/dt [Drug Therapy];hepatitis A/dt [Drug Therapy];hepatitis B/dt [Drug Therapy];human;liver cancer/dt [Drug Therapy];liver cirrhosis/dt [Drug Therapy];liver disease/dt [Drug Therapy];liver transplantation;review;Wilson disease/dt [Drug Therapy];colchicine/dt [Drug Therapy];colestyramine/dt [Drug Therapy];cyclosporin A/dt [Drug Therapy];doxorubicin/dt [Drug Therapy];fluorouracil/dt [Drug Therapy];interferon/dt [Drug Therapy];levamisole/dt [Drug Therapy];mebendazole/dt [Drug Therapy];methylprednisolone/dt [Drug Therapy];metronidazole/dt [Drug Therapy];mitomycin C/dt [Drug Therapy];penicillamine/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy],"Froehlich, F.;Margalith, D.;Gonvers, J. J.;Fasel, J.;Mosimann, F.;Lavanchy, D.;Bauer, J.;Schnegg, J. F.;Bauerfeind, P.;Frei, A.;Guyot, J.;Vuillamoz, D.;Nicolet, M.;Fried, M.;Duroux, P.;Dorta, G.;Bretholz, A.;Armstrong, D.;Blum, A. L.",1991,,,0,0,
2695,New developments in therapeutic chelating agents as antidotes for metal poisoning,"An examination of the studies on therapeutic chelating agents that have been carried out during the last decase reveals that extensive efforts have been made to develop compounds superior to those previously available for the treatment of acute and chronic intoxication by many metals. These metals include primarily iron, plutonium, cadmium, lead, and arsenic, but also many other elements for which acute and chronic intoxication is less common. These studies have revealed the importance of several additional factors of importance in the design of such compounds and have led to many new compounds of considerable clinical promise. An additional development has been the introduction of previously developed chelating agents for use with certain metals on a broader scale.","Antidotes for toxic metals;Cadmium intoxication;Chelating agents;Iron overload;Lead intoxication;Metal antidotes;Metal chelators;Plutonium mobilization;Stability constants;Toxic metal excretion;Wilson's disease;human;intoxication/dt [Drug Therapy];priority journal;review;Wilson disease/dt [Drug Therapy];2,3 dihydroxybenzoic acid derivative/dt [Drug Therapy];aluminum/to [Drug Toxicity];arsenic/to [Drug Toxicity];cadmium/to [Drug Toxicity];chelating agent/dt [Drug Therapy];cisplatin/to [Drug Toxicity];cyclam/dt [Drug Therapy];cyclam s/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];deferoxamine mesylate;diethyldithiocarbamic acid/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];dithiocarbamic acid derivative/dt [Drug Therapy];edetic acid/dt [Drug Therapy];iron/to [Drug Toxicity];lead/to [Drug Toxicity];metal/to [Drug Toxicity];nickel/to [Drug Toxicity];penicillamine/dt [Drug Therapy];pentetic acid/dt [Drug Therapy];plutonium/to [Drug Toxicity];succimer/dt [Drug Therapy];unclassified drug;unithiol/dt [Drug Therapy];uranium/to [Drug Toxicity]","Jones, M. M.",1991,,,0,0,
2696,The management of hepatolenticular degeneration. [Portuguese],,article;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Reis Barbosa, E.;Scaff, M.;Martins Canelas, H.",1991,,,0,0,
2697,Does orthotopic liver transplantation heal Wilson's disease? Clinical follow-up of two liver-transplanted patients,"Two patients with Wilson's disease (WD) underwent orthotopic liver transplantation, one for subacute liver failure and the other for severe oesophageal haemorrhage. After transplantation both patients fully recovered within five months, and copper metabolism returned to normal. Follow-up examinations were continued for 4 and 6 years. Clinical as well as electrophysiological testing in these two patients yielded better results than in most of 12 WD-patients being conventionally treated for a similar period or even longer.",Liver transplantation;Motor impairment;Normalization of copper metabolism;Wilson's disease;adult;article;case report;electroencephalography;evoked response;female;human;human tissue;motor dysfunction/di [Diagnosis];motor dysfunction/et [Etiology];nuclear magnetic resonance imaging;oral drug administration;priority journal;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy],"Hefter, H.;Rautenberg, W.;Kreuzpaintner, G.;Arendt, G.;Freund, H. J.;Pichlmayr, R.;Strohmeyer, G.",1991,,,0,0,
2698,Recurrent abortion and the diagnosis of Wilson disease,"We describe the first patient with Wilson disease and recurrent abortion who was effectively treated with oral zinc for both conditons. Between the ages of 21-26, this patient experienced seven successive unexplained abortions. At age 27, neurologic signs and liver function disturbances appeared. Wilson disease was diagnosed when Kayser-Fleischer rings were detected in the cornea. Decoppering therapy was instituted with zinc sulfate per os. By the age of 31, hepatic and neurologic signs had vanished. The patient conceived, and after an uncomplicated eighth pregnancy she delivered her first healthy child. Two years later, a ninth pregnancy was equally successful. The chance that Wilson disease may be the cause of recurrent abortion is small. However, because the disease is fatal if left untreated and because it is an underdiagnosed disease, we recommend screening for Wilson disease in cases of unexplained recurrent abortion when family history demonstrates consanguinity or neurologic, psychiatric, and/or liver disorders. A strategy to this end is proposed.",adult;article;case report;female;human;oral drug administration;priority journal;recurrent abortion;Wilson disease;zinc sulfate/dt [Drug Therapy],"Schagen van Leeuwen, J. H.;Christiaens, G. C. M. L.;Hoogenraad, T. U.",1991,,,0,0,
2699,"Wilson's disease, Kayser and Fleischer's sign and Walshe's treatment","Wilson's disease is named after Kinnier Wilson (1878-1937), a famous British neurologist. It is an inherited condition, due to an excess of copper in the liver and brain. The mechanism is unknown, but the gene has been mapped to chromosome 13. The worldwide prevalence is about 30 per million. Patients present with liver disease and/or neuropsychiatric manifestations. Early diagnosis is crucial because there is an effective treatment. This treatment, usually with penicillamine, must be continued for life and without interruption. Liver transplantation may be lifesaving in patients with fulminant hepatitis, or with severe liver disease which is unresponsive to treatment.",brain;chromosome 13;early diagnosis;gene;hepatitis/th [Therapy];liver disease;liver transplantation;neurologic disease;neuropsychiatry;note;pathology;priority journal;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];Wilson disease/th [Therapy];ceruloplasmin/do [Drug Dose];copper;penicillamine/dt [Drug Therapy],"McIntyre, N.",1991,,,0,0,
2700,Neurological and neuropsychiatric spectrum of Wilson's disease: A prospective study of 45 cases,"Forty-five patients with Wilson's disease (WD) were prospectively studied: 27 had neurological deficits, 12 hepatic signs, and 6 were asymptomatic. Kayser-Fleischer rings occurred in 23 of the neurological patients and in only 4 of the hepatic patients. Neurological features were extremely variable with respect to frequency and severity. Most frequent were dysdiadochokinesis (25 patients), dysarthria (23), bradykinesia (17), and posture tremor (14). Fifteen, mainly long-term treated patients, presented with rather discrete neurological abnormalities which predominantly consisted of dysarthria and various forms of tremor. Eight patients had a parkinsonian type of neurological WD associated with signs of an organic mood syndrome. Three patients were predominantly hyperkinetic, presenting with dystonic and choreatic movements. In 1 patient, ataxia was the predominant neurological feature. There was a clear-cut correlation between the severity of neurological impairment and the restriction in functional capacity. Nine patients were not able to engage in salaried employment or were retired. Psychiatric symptoms and behavioural disorders were common, varying from mild personality and psychological disturbances to severe psychiatric illness resembling psychotic disorders and major depressive syndromes. Significant mental deterioration was not found in the patients. Disturbances of mood were observed in 12 patients, all of whom had neurological abnormalities. There was a history of an attempted suicide in 7 patients, and a history of an organic delusional syndrome in 3.",adolescent;adult;article;chorea/et [Etiology];clinical article;depression/et [Etiology];dystonia/et [Etiology];female;human;lens disease/di [Diagnosis];lens disease/dt [Drug Therapy];liver injury/di [Diagnosis];liver injury/dt [Drug Therapy];male;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy],"Oder, W.;Grimm, G.;Kollegger, H.;Ferenci, P.;Schneider, B.;Deecke, L.",1991,,,0,0,
2701,Retinal changes in Wilson's disease. [German],,adult;case report;conference paper;human;male;oral drug administration;retina macula lutea;retinopathy/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Rossa, V.",1991,,,0,0,
2702,Wilson's disease,,editorial;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Nazer, H.",1991,,,0,0,
2703,Wilson's disease in Saudi Arabia: Report of a Saudi Arab family,"A Saudi family with Wilson's disease (hepatolenticular degeneration) is described. The index case presented with anicteric hepatitis and hydrops of the gallbladder. Neurological involvement appeared later. The diagnosis of Wilson's disease was based on the presence of Kayser-Fleischer rings, a low serum ceruloplasmin level, and an elevated urinary copper concentration. Histological examination of the liver biopsy specimen revealed active cirrhosis. Acute hepatic failure developed during D-penicillamine therapy. Continuation of the drug at a lower dose, along with other supportive measures, was successful in reversing this. After three years of therapy, the index patient's neurological signs disappeared, and liver function and gallbladder size and function returned to normal. Family screening revealed that three other siblings have the disease, and all have been treated with D-penicillamine. The parents are related but are asymptomatic. An unusual feature of the index case was the presence of a distended nonfunctioning gallbladder that reverted to normal with decoppering. Although D-penicillamine treatment possibly precipitated the acute hepatic failure, paradoxically it was also successful in treating it.",adolescent;adult;article;clinical article;family study;female;human;male;preschool child;Saudi Arabia;Wilson disease/cn [Congenital Disorder];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination],"Ahmad, F. E. R. E.;El-Tayeb, A. A.;Satti, M. B.",1991,,,0,0,
2704,The ultrasonographic appearance of the liver in two patients with Wilson's disease presented as fulminant hepatitis,,adolescent;adult;article;autopsy;case report;echography;female;hepatitis;human;liver cirrhosis/di [Diagnosis];oral drug administration;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ishibashi, H.;Tsuchiya, Y.;Dohmen, K.;Shimamura, R.;Kondo, H.;Y, H. Hirata;Kudo, J.",1991,,,0,0,
2705,The role of zinc in disease. [French],,acrodermatitis enteropathica;article;food intake;human;intravenous drug administration;oral drug administration;Wilson disease;zinc deficiency/di [Diagnosis];zinc deficiency/dt [Drug Therapy];zinc deficiency/et [Etiology];zinc sulfate/ad [Drug Administration];zinc sulfate/dt [Drug Therapy],"Conri, C.",1991,,,0,0,
2706,"A comparison of the effects of penicillamine, trientine, and trithiomolybdate on [<sup>35</sup>S]-labeled metallothionein in vitro; Implications for Wilson's disease therapy",,animal tissue;article;liver cytosol;male;nonhuman;rat;Wilson disease;copper/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];penicillamine/cm [Drug Comparison];penicillamine/pd [Pharmacology];trientine/cm [Drug Comparison];trientine/pd [Pharmacology];trithiomolybdic acid/cm [Drug Comparison];trithiomolybdic acid/pd [Pharmacology];unclassified drug,"McQuaid, A.;Mason, J.",1991,,http://dx.doi.org/10.1016/0162-0134%2891%2980002-Y,0,0,
2707,Zinc sulphate therapy for Wilson's disease after acute deterioration during treatment with low-dose D-penicillamine,"A 30-year-old woman with Wilson's disease was treated with low-dose D-penicillamine. After 12 days, treatment was changed to zinc sulphate because of severe neurological deterioration. The patient subsequently improved within a few days. During a follow-up period of 20 months, the effectiveness of therapy was evaluated by measuring copper and zinc levels in plasma and urine, and by <sup>64</sup>Cu-loading tests. We conclude that sulphate therapy may be a satisfactory alternative, even when rapid deterioration occurs in the early stages of D-penicillamine treatment.",<sup>64</sup>Cu-loading test;D-penicillamine;Wilson's disease;zinc sulphate;adult;article;case report;diagnostic test;female;human;oral drug administration;priority journal;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];copper 64;penicillamine/dt [Drug Therapy];zinc/ec [Endogenous Compound];zinc sulfate/dt [Drug Therapy],"Veen, C.;Van Den Hamer, C. J. A.;De Leeuw, P. W.",1991,,,0,0,
2708,Metabolic liver disease,"Diseases that fall into the category of metabolic liver diseases are generally considered to include disorders of hepatic synthesis and degradation or regulation of a diverse variety of endogenous compounds. The spectrum of abnormalities ranges from disorders of enzyme production and release (ie, alpha<inf>1</inf>-antitrypsin deficiency) to disorders of mineral disposition (ie, Wilson's disease and genetic hemochromatosis). Recent key publications that advance our understanding of these diseases are presented in this section. Although neonatal hemochromatosis may not strictly fit the definition of a metabolic disorder as outlined previously, its cause remains unknown, and hence this entity is included because of its phenotypic similarity to the recognized metabolic disorder, genetic hemochromatosis.",alpha antitrypsin deficiency/et [Etiology];child;copper metabolism;Crigler Najjar syndrome/et [Etiology];Crigler Najjar syndrome/su [Surgery];cystic fibrosis/dt [Drug Therapy];enzyme defect;hemochromatosis/di [Diagnosis];hemochromatosis/et [Etiology];human;inborn error of metabolism;infant;iron metabolism;liver disease/et [Etiology];major clinical study;oral drug administration;perinatal morbidity;review;tyrosinemia/et [Etiology];tyrosinemia/su [Surgery];tyrosinemia/th [Therapy];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];trientine/dt [Drug Therapy];ursodeoxycholic acid/do [Drug Dose];ursodeoxycholic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Berg, C. L.;Gollan, J. L.",1991,,,0,0,
2709,Wilson's disease: Report of four cases,,adolescent;article;case report;child;chronic liver disease;dysarthria;female;human;male;Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];cortisone/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Anwarullah, A. K. M.;Ahmed, M.;Islam, M. R.",1991,,,0,0,
2710,Intellectual functioning in treated Wilson's disease [2],,adolescent;adult;clinical article;cognition;human;intelligence;letter;oral drug administration;priority journal;school child;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Medalia, A.;Scheinberg, I. H.",1991,,,0,0,
2711,Comparison of functional and structural brain disturbances in Wilson's disease,"We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD.",adolescent;adult;article;brain;clinical article;evoked brain stem auditory response;evoked somatosensory response;evoked visual response;female;human;male;mouse;nuclear magnetic resonance imaging;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Grimm, G.;Prayer, L.;Oder, W.;Ferenci, P.;Madl, Ch;Knoflach, P.;Schneider, B.;Imhof, H.;Gangl, A.",1991,,,0,0,
2712,Successful treatment of a patient with hepatolenticular degeneration with the terminal stage of liver disease. [Russian],,adult;article;case report;hepatic encephalopathy/co [Complication];hepatic encephalopathy/th [Therapy];human;intensive care;male;multimodality cancer therapy;plasmapheresis;Wilson disease/co [Complication];Wilson disease/th [Therapy];penicillamine/ad [Drug Administration];prednisolone/ad [Drug Administration];sulfate/ad [Drug Administration];zinc/ad [Drug Administration];zinc sulfate,"Gorelov, V. G.;Vakharlovskii, V. G.;Razevig, N. D.;Vorob'ev, A. I.",1991,Apr,,0,0,
2713,Connections between articular and liver pathology. [Italian],,alcohol liver disease;amyloidosis;articular cartilage;human;immune system;liver;rheumatic disease/dt [Drug Therapy];rheumatoid arthritis;sarcoidosis;short survey;Wilson disease;acetylsalicylic acid/dt [Drug Therapy];allopurinol/dt [Drug Therapy];azathioprine/dt [Drug Therapy];chlorambucil/dt [Drug Therapy];cyclosporin A/dt [Drug Therapy];gold/dt [Drug Therapy];interferon/dt [Drug Therapy];mercaptopurine/dt [Drug Therapy];methotrexate/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenylbutazone/dt [Drug Therapy],"Porzio, V.",1991,,,0,0,
2714,Copper in faeces - a marker of the effectiveness of zinc treatment in Wilson's disease. [Czech],,article;clinical article;feces;human;oral drug administration;Wilson disease/dt [Drug Therapy];copper/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Dastych, M.",1991,,,0,0,
2715,Drug-induced lupus-like serologic abnormalities in Wilson disease patients. [Italian],,adult;article;case report;female;human;systemic lupus erythematosus/et [Etiology];systemic lupus erythematosus/si [Side Effect];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy],"Demelia, L.;Vallebona, E.;Perpignano, G.;Pitzus, F.",1991,,,0,0,
2716,Early diagnosis is crucial for the prognosis of Wilson's disease. [Swedish],,adolescent;adult;article;case report;female;human;liver transplantation;prognosis;time;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ceruloplasmin/an [Drug Analysis];penicillamine/ad [Drug Administration],"Olsson, R.;Lindgren, A.;Frizell, M.",1991,23 Jan,,0,0,
2717,Electrocautery as a successful treatment for penicillamine-induced elastosis perforans serpiginosa,This case report describes the successful treatment of elastosis perforans serpiginosa with electrocautery in a patient with Wilson's disease treated with long-term penicillamine.,adult;article;axilla;case report;cauterization;elastosis/si [Side Effect];elastosis/th [Therapy];elastosis perforans serpiginosa;follow up;human;male;neck;penicillamine/ae [Adverse Drug Reaction],"Layton, A. M.;Cunliffe, W. J.",1991,,,0,0,
2718,Liver and biliary tract disease: Advances in 1990. [German],,biliary tract disease/dt [Drug Therapy];biliary tract disease/su [Surgery];biliary tract disease/th [Therapy];cholecystectomy;chronic active hepatitis/dt [Drug Therapy];gallstone/su [Surgery];gallstone/th [Therapy];human;laparoscopy;lithotripsy;liver abscess;liver cancer;liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver disease/th [Therapy];liver transplantation;primary biliary cirrhosis;review;Wilson disease;acetylsalicylic acid/dt [Drug Therapy];benzoic acid/dt [Drug Therapy];colchicine/dt [Drug Therapy];colestyramine/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];cyclosporin/dt [Drug Therapy];diuretic agent/dt [Drug Therapy];doxorubicin/dt [Drug Therapy];flumazenil/dt [Drug Therapy];fluorouracil/dt [Drug Therapy];glyceryl trinitrate/dt [Drug Therapy];interferon/dt [Drug Therapy];lactulose/dt [Drug Therapy];levamisole/dt [Drug Therapy];mebendazole/dt [Drug Therapy];methylprednisolone/dt [Drug Therapy];metronidazole/dt [Drug Therapy];mitomycin C/dt [Drug Therapy];penicillamine/dt [Drug Therapy];propranolol/dt [Drug Therapy];somatostatin/dt [Drug Therapy];terlipressin/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];vasopressin/dt [Drug Therapy];zinc/dt [Drug Therapy],"Froehlich, F.;Margalith, D.;Gonvers, J. J.;Fasel, J.;Mosimann, F.;Lavanchy, D.;Bauer, J.;Schnegg, J. F.;Bauerfeind, P.;Frei, A.;Guyot, J.;Vuillamoz, D.;Nicolet, M.;Fried, M.;Duroux, P.;Dorta, G.;Bretholz, A.;Armstrong, D.;Blum, A. L.",1991,,,0,0,
2719,The nigrostriatal dopaminergic pathway in Wilson's disease studied with positron emission tomography,"Movement disorders, including Parkinsonism, are prominent features of neurological Wilson's disease (WD). This suggests there may be dysfunction of the nigrostriatal dopaminergic pathway. To explore this possibility, five patients were studied using positron emission tomography (PET) with <sup>18</sup>F-6-fluorodopa (6FD), and magnetic resonance imaging (MRI). We calculated striatal 6FD uptake rate constants by a graphical method and compared the results with those of 18 normal subjects. It was found that four patients with symptoms all had abnormally low 6FD uptake, and the one asymptomatic patient had normal uptake. PET evidence for nigrostriatal dopaminergic dysfunction was present even after many years of penicillamine treatment. It is concluded that the nigrostriatal dopaminergic pathway is involved in neurological WD.",adult;article;clinical article;corpus striatum;dopaminergic system;female;human;male;nuclear magnetic resonance imaging;positron emission tomography;priority journal;substantia nigra;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine,"Snow, B. J.;Bhatt, M.;Martin, W. R. W.;Li, M. D.;Calne, D. B.",1991,,,0,0,
2720,Wilson's disease with neurological impairment but no Kayser-Fleischer rings [38],,adult;case report;human;letter;male;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Willeit, J.;Kiechl, S. G.",1991,,,0,0,
2721,Wilson's disease: Computed tomography and magnetic resonance imaging findings,"The condition of a patient with Wilson's disease was evaluated by magnetic resonance imaging (MRI) on initial presentation of the illness. The examination revealed mild atrophy of the superior vermis. Symmetric areas of increased signal intensity on T2-weighted images were detected in the anterior thalami, mesencephalic tectum and tegmentum. Marked symmetric hypointensities appeared in the head of caudate, pallida, substantia nigra and red nuclei. The histopathology of Wilson's disease suggests that these hypointensities may be secondary to the presence of protein-bound copper.",computed tomography;magnetic resonance imaging;Wilson's disease;article;brain atrophy;computer assisted tomography;nuclear magnetic resonance imaging;oral drug administration;priority journal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Abdollah, A.;Tampieri, D.;Melanson, D.",1991,,,0,0,
2722,Intestinal absorption and urinary excretion of triethylenetetramine for Wilson's disease in rat. [Japanese],,animal experiment;animal model;article;diet restriction;drug absorption;drug binding;drug excretion;drug metabolism;intravenous drug administration;nonhuman;oral drug administration;rat;urine;Wilson disease/dt [Drug Therapy];amikacin;drug metabolite;trientine/ad [Drug Administration];trientine/cm [Drug Comparison];trientine/cr [Drug Concentration];trientine/dt [Drug Therapy];trientine/pk [Pharmacokinetics],"Kobayashi, M.;Sugawara, M.;Saitoh, H.;Iseki, K.;Miyazaki, K.",1990,,,0,0,
2723,Wilson's disease -Two clinicopathological features with different prognosis-. [Japanese],,adolescent;adult;article;clinical article;female;human;kidney failure;liver failure/di [Diagnosis];male;prognosis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ichimiya, H.;Higuchi, T.;Hishida, N.;Hayashi, H.;Sakamoto, N.;Urrutia, F. J. H.",1990,,,0,0,
2724,Zinc therapy of Wilson's disease VIII: Dose response studies,"Our purpose is to establish a rational basis for the dose of zinc acetate to recommend for long-term maintenance therapy of Wilson's disease. Zinc acts by inducing intestinal metallothionein, which blocks copper absorption. Fifty mg. of zinc three times daily has been uniformly effective in Wilson's disease as evaluated by copper balance, blockade of absorption of orally administered <sup>64</sup>copper, and urine, plasma, and hepatic copper levels. Here we have evaluated several lower doses of zinc, using copper balance and <sup>64</sup>copper absorption. Doses of 25 mg four times, 25 mg three times, and 50 mg two times daily are also effective but leave little safety margin, because 25 mg two times and 75 mg one time daily are not effective. Based upon this work, we recommend 50 mg of elemental zinc three times daily as the standard dose for the maintenance therapy of Wilson's disease.",<sup>64</sup>copper;copper;copper balance;metallothionein;article;clinical article;dose response;human;oral drug administration;priority journal;Wilson disease/dt [Drug Therapy];zinc/do [Drug Dose];zinc/dt [Drug Therapy],"Brewer, G. J.;Yuzbasiyan-Gurkan, V.;Dick, R.",1990,,,0,0,
2725,Liver and biliary tract diseases: Advancements during 1989. [German],,biliary cirrhosis;bleeding;brain disease;hepatitis B;human;lithotripsy;liver disease/dt [Drug Therapy];liver transplantation;review;Wilson disease;colchicine/dt [Drug Therapy];colestyramine/dt [Drug Therapy];flumazenil/dt [Drug Therapy];methotrexate/dt [Drug Therapy];metronidazole/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];rifampicin/dt [Drug Therapy];somatostatin/dt [Drug Therapy];terlipressin;ursodeoxycholic acid/dt [Drug Therapy];vasopressin/dt [Drug Therapy],"Bretholz, A.;Dorta, G.;Margalith, D.;Gonvers, J. J.;Fasel, J.;Pettavel, J.;Lavanchy, D.;Restellini, A.;Schnegg, J. F.;Bauerfeind, P.;Guyot, J.;Ollyo, J. B.;Frei, A.;Pusztaszeri, G.;Nicolet, M.;Jehle, E.;Castiglione, F.;Blum, A. L.",1990,,,0,0,
2726,Treatment of chronic hepatitis. [German],,autoimmunity;chronic hepatitis/dt [Drug Therapy];chronic hepatitis/et [Etiology];hemochromatosis;hepatobiliary system infection;human;priority journal;short survey;virus hepatitis;Wilson disease;alpha interferon/dt [Drug Therapy];corticosteroid/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Blum, H. E.",1990,,,0,0,
2727,"Wilson disease presenting as fulminant hepatic failure, acute hemolytic anemia and renal failure: report of one case. [Chinese]","Wilson disease presenting as fulminant hepatic failure, severe hemolysis and renal failure is rare in the literature. A ten-year-old boy--complaining of abdominal pain, jaundice, tea-colored urine, and anemia was admitted to this hospital; examination showed Kayser-Fleischer rings, anemia associated with hemolysis, mildly elevated serum transaminases, extremely elevated bilirubin levels, low serum ceruloplasmin level, slightly elevated serum copper, excessive 24-hour urine copper excretion, and severe renal function insufficiencies. Under the impression of Wilson disease with fulminant hepatic failure, the patient was treated by oral D-penicillamine 1 gm per day, intravenous zinc sulphate (about 8 mg per day elemental zinc), and given other supportive treatment. Unfortunately, the patient died of hepatic failure complicated with septic shock 21 days after the onset of symptoms. Autopsy found liver copper content was 586.92 ug/gm dry weight and kidney copper content: 300.19 ug/gm dry weight, abnormally high as compared with normal tissue. A review of the literature led to conclusion that the best treatment for Wilson fulminant hepatic failure is liver transplantation.",acute disease;article;case report;child;hemolytic anemia;hepatic encephalopathy;human;kidney disease;male;Wilson disease/di [Diagnosis],"Tseng, C. L.;Tsai, S. L.;Lin, K. H.;Chang, M. H.;Wang, T. R.;Hsu, Y. H.;Hsu, H. C.",1990,1990,,0,0,
2728,Routine screen for Wilson's disease?,,case report;female;human;letter;male;priority journal;psychological aspect;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Scheinberg, I. H.",1990,,,0,0,
2729,The effect of D-penicillamine on metallothionein mRNA levels and copper distribution in mouse hepatocytes,"Penicillamine increases the levels of metallothionein (MT) mRNA in a time and concentration dependent manner without altering either the rate of copper uptake or the amount of copper within the cell. The effect is dependent on the presence of intracellular copper, however, since depletion of copper by chelators blocks the effect, and does not alter the ability of dexamethasone to stimulate mRNA production. Penicillamine did not alter the distribution of <sup>64</sup>Cu in the hepatocytes, as measured by fast protein liquid chromatography (FPLC), although the pattern may be affected by the amount of MT present. The data indicates that penicillamine removes copper from some intermediary ligand, thereby making it available to induce metallothionein. It is possible that this is part of the therapeutic action of the chelator in the treatment of Wilson's disease.",copper binding;copper transport;copper uptake;diamsar;liver;metallothionein 1;Wilson's disease;animal cell;article;cell culture;chelation;copper metabolism;liver cell;mouse;nonhuman;priority journal;Wilson disease;dexamethasone;messenger RNA;metallothionein;penicillamine/pd [Pharmacology];radioisotope;zinc,"McArdle, H. J.;Kyriakou, P.;Grimes, A.;Mercer, J. F. B.;Danks, D. M.",1990,,http://dx.doi.org/10.1016/0009-2797%2890%2990074-W,0,0,
2730,Perspectives on Wilson's disease,,article;human;priority journal;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];zinc/dt [Drug Therapy],"Sternlieb, I.",1990,,http://dx.doi.org/10.1002/hep.1840120526,0,0,
2731,Clinical aspects of Wilson's disease,,adult;article;case report;female;human;inheritance;priority journal;symptomatology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Schoen, R. E.;Sternlieb, I.",1990,,,0,0,
2732,Pancreaticobiliary secretion of zinc and copper in normal persons and patients with Wilson's disease,"The objectives of this study were (1) to examine basal and cholecystokinin-stimulated pancreaticobiliary secretion of zinc in normal subjects with zinc-adequate and zinc-deficient diets, and (2) to investigate whether basal and stimulated secretion of zinc was abnormal in patients with Wilson's disease before and after zinc therapy. Gastroduodenal intubation was performed in six healthy subjects and five patients with Wilson's disease. After intravenous infusion of octapeptide of cholecystokinin (40 ng/kg/hr) the pancreaticobiliary secretion of zinc increased from a basal rate of 283.1 +/- 75.8 nmol/L/min to a peak of 716.6 +/- 175.3 nmol/L/min in normal subjects. Normal subjects with a zinc-deficient diet had both lower basal (66.8 +/- 15.8 nmol/L/min) and stimulated (559.5 +/- 31 nmol/L/min) pancreaticobiliary secretion of zinc than with a zinc-sufficient diet. In contrast to the markedly reduced pancreaticobiliary secretion of copper, patients with Wilson's disease not treated with zinc had normal basal (226.6 +/- 126 nmol/L/min) and stimulated (728.7 +/- 195.5 nmol/L/min) zinc secretion. These studies indicate that a considerable amount of zinc is being secreted in pancreaticobiliary fluid in healthy subjects and there was no impairment of zinc secretion in patients with Wilson's disease. Our data also indicate that pancreaticobiliary secretion of zinc is dependent on the zinc status of the subjects, suggesting that endogenous secretion of zinc may play a significant role in the homeostasis of zinc.",article;bile secretion;clinical article;human;human experiment;intravenous drug administration;pancreas secretion;priority journal;Wilson disease;cholecystokinin octapeptide;copper;zinc,"Lee, H. H.;Hill, G. M.;Sikha, V. K. N. M.;Brewer, G. J.;Prasad, A. S.;Owyang, C.",1990,,,0,0,
2733,Hepatolenticular degeneration. [Serbian],"Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.",adolescent;adult;article;child;human;pathophysiology;preschool child;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy],"Zudenigo, D.;Relja, M.",1990,,,0,0,
2734,Therapeutic approaches to Wilson's disease. [Hebrew],,editorial;human;Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Meiner, Z.",1990,1 Mar,,0,0,
2735,Hepatology. [French],,article;biliary cirrhosis/dt [Drug Therapy];cholangitis/dt [Drug Therapy];hepatitis/dt [Drug Therapy];human;liver metastasis/dt [Drug Therapy];stone formation;Wilson disease/dt [Drug Therapy];acetylsalicylic acid/dt [Drug Therapy];colchicine/dt [Drug Therapy];mebendazole/dt [Drug Therapy];methotrexate/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];propranolol/dt [Drug Therapy];rifampicin/dt [Drug Therapy];terlipressin/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy],"Margalith, D.;Gonvers, J. J.;Fasel, J.;Pettavel, J.;Lavanchy, D.;Restellini, A.;Bretholz, A.;Bauerfeind, P.;Guyot, J.;Ollyo, J. B.;Frei, A.;Pusztaszeri, G.;Nicolet, M.;Jehle, E.;Blum, A. L.",1990,,,0,0,
2736,Wilson's disease: critical deterioration with high-dosage parenteral penicillamine treatment. [German],"A 31-year-old man with Wilson's disease, not treated for the past 4 1/2 years, was admitted to hospital with brain concussion after a fall. While receiving penicillamine, 1 g i.v. four times daily, the neurological signs worsened and akinesia, mutism, tachy- and bradyarrhythmias, as well as transitory respiratory insufficiency developed. Serum copper concentration on the sixth day of treatment was markedly decreased to 28 mug/dl, rising to 60 mug/dl on the ninth day. 24-hour urinary copper excretion was at first 4500-5000 mug. Only after drastic reduction of the penicillamine dosage to 600 mg three times daily was there any improvement and after 11 weeks the patient was again able to walk and discharged. Marked, mainly hepatic, copper depletion from the high penicillamine dosage was the likely cause of the patient's initial deterioration. To avoid cerebral complications penicillamine should be administered in gradually increasing doses.",adult;akinesia/co [Complication];article;case report;drug overdose;female;heart rate;heredity;human;intravenous drug administration;male;mutism/co [Complication];priority journal;Wilson disease;penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy],"Hilz, M. J.;Druschky, K. F.;Bauer, J.;Neundorfer, B.;Schuierer, G.",1990,,,0,0,
2737,Unusual immunologically-induced asthma forms. [German],,asthma/et [Etiology];asthma/si [Side Effect];conference paper;human;immunofluorescence;major clinical study;primary biliary cirrhosis;rheumatoid arthritis;Wilson disease;penicillamine/ae [Adverse Drug Reaction],"Storch, W.",1990,,,0,0,
2738,Clinical analysis of 418 patients with Wilson's disease in traditional Chinese medicine and Western medicine therapy. [Chinese],"From 1974 to 1988, 418 cases of Wilson's disease were treated with TCM-WM in our hospital. 147 cases were of Wilson's type; 149 cases were of pseudosclerosis type; 40 cases were of abdominal and hepatocerebral type; 21 cases were of choreoathetosis type and 21 cases of other types. After a course of treatment for 3 to 6 months, 103 patients showed marked improvement and 286 made some improvement, but no effect was found in 22 patients and 7 deaths were observed. The results were as follows: (1) The mortality in the severe and moderate groups were significantly higher than the mild (P less than 0.05) and the marked effective rate was less than the latter (P less than 0.01). (2) The marked effective rate was lower in abdominal and hepatocerebral type, and no significant difference was found in recovery rate between Wilson's type and pseudosclerosis type.",adolescent;adult;article;child;female;human;male;middle aged;multimodality cancer therapy;preschool child;Wilson disease/dt [Drug Therapy];herbaceous agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];succimer/dt [Drug Therapy];sulfate/dt [Drug Therapy];thiol derivative/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc sulfate,"Yang, R.",1990,Mar,,0,0,
2739,Wilson's disease and liver transplantation. Does penicillamine and zinc sulphate association modify the prognosis?. [Italian],,article;case report;child;drug efficacy;human;liver cirrhosis/dt [Drug Therapy];liver failure/dt [Drug Therapy];liver transplantation;male;prognosis;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Zancan, L.;Menara, M.;Monciotti, C.;Rigon, F.;Sturniolo, G. L.",1990,,,0,0,
2740,Wilson's disease in an Australian Aborigine,"Wilson's disease is due to a genetically determined defect inherited as an autosomal recessive trait. Most reported cases have been caucasoid. This report describes a case of Wilson's disease in an Australian Aboriginal girl, only the second such case reported.",Aboriginal;autosomal recessive;copper homeostasis;Wilson's disease;article;Australia;case report;child;female;human;Wilson disease/dt [Drug Therapy];penicillamine,"Crawford, D. H. G.;Shepherd, R.;Cooksley, W. G. E.;Patrick, M.;Powell, L. W.",1990,,,0,0,
2741,Wilson's disease in adults with cirrhosis but no neurological abnormalities,,adult;article;blood level;case report;female;human;liver cirrhosis;liver level;male;priority journal;Wilson disease;copper;penicillamine/dt [Drug Therapy];radioisotope;zinc sulfate/dt [Drug Therapy],"Danks, D. M.;Metz, G.;Sewell, R.;Prewett, E. J.",1990,,,0,0,
2742,Haemolytic anaemia in Wilson's disease. [Portuguese],,adolescent;article;case report;female;hemolytic anemia;human;thrombocytopenia/si [Side Effect];Wilson disease;penicillamine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy],"Pinto, A.;Carneiro Chaves, F.;Moreira, M.;Flores, A.;Falcao de Freitas, A.",1990,,,0,0,
2743,Cerebral abnormalities in Wilson's disease as evaluated by ultra-low-field magnetic resonance imaging and computerized image processing,"The cerebral involvement of a 13-yr-old boy with Wilson's disease was serially evaluated during the first 18 mo of D-penicillamine treatment. An ultra-low-field magnetic resonance imaging (ULF MRI) system, operating at 0.02 T, with computerized image processing was used. The half-yr period prior to the clinical diagnosis was set, the patient had showed poor school performance, emotional lability, deteriorating handwriting, progressively slow, gross, and fine motor functions, and a fixed rigid smile. No overt signs of liver disease were found. With D-penicillamine treatment (1-1.5 g/d) a continuous improvement was seen. The pretreatment MRI investigation showed pronounced pathological transformation in the basal ganglia. However, changes were seen also in most other parts of the brain indicating diffuse involvement. During treatment the computerized MR images became gradually more normal. The current magnetic resonance imaging system with computerized image processing is a sensitive and simple method for evaluation of subtle parenchymal changes of the brain.",adolescent;article;brain;case report;diagnosis;human;image processing;male;nuclear magnetic resonance imaging;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];vitamin B group/dt [Drug Therapy],"Limme, T.;Agartz, I.;Saaf, J.;Wahlund, L. O.",1990,,http://dx.doi.org/10.1016/0730-725X%2890%2990020-3,0,0,
2744,D-penicillamine induced obstructive laryngeal edema and bronchial asthma,,article;asthma/et [Etiology];asthma/si [Side Effect];controlled study;edema/et [Etiology];edema/si [Side Effect];human;human tissue;larynx stenosis/et [Etiology];larynx stenosis/si [Side Effect];major clinical study;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Storch, W.",1990,,,0,0,
2745,Anti-lymphocytic antibodies in autoimmune chronic active hepatitis starting in childhood,Anti-lymphocytic antibodies (ALA) have been described in a variety of autoimmune disorders. We have investigated the presence of ALA in autoimmune chronic active hepatitis (aCAH) starting in childhood. Using a modified Terasaki technique ALA were found in 17 of 18 patients with aCAH but in only one of 15 patients with alpha-1-anti-trypsin deficiency or Wilson's disease and three of 27 age-matched healthy controls (P < 0.0005 for both). Sera from 12 patients with uncontrolled aCAH had significantly higher cytotoxicity values than sera from six children with inactive disease (P < 0.01). ALA were directed to T but not B lymphocytes and were not reactive with specific HLA antigens. No preferential killing was observed against CD4 or CD8 positive T lymphocytes. Characterization of ALA revealed them to be cold-reactive IgM. The possible role of ALA in aCAH is discussed.,adolescent;adult;autoimmunity;child;chronic hepatitis;clinical article;controlled study;female;human;human cell;male;priority journal;serum;azathioprine/dt [Drug Therapy];lymphocyte antibody;penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy],"Donaldson, P. T.;Hussain, M. J.;Mieli-Vergani, G.;Mowat, A. P.;Vergani, D.",1989,,,0,0,
2746,Visual and brain stem auditory evoked responses in Wilson's disease,Sensory evoked potentials were studied in 15 patients with Wilson's disease. Thirteen patients were investigated with pattern reversal visual stimulation. A prolonged P 100 latency of the VEP was present in 7 patients. Braim stem auditory responses were evoked in 12 patients. Prolongation of III-V and I-V interpeak latency was found in 8 patients. The evoked potential studies demonstrated subclinical disturbances in optic and caudal brainstem auditory pathways. Further studies are in progress to evaluate the role of these techniques in monitoring the therapy of newly diagnosed cases.,adolescent;adult;auditory stimulation;central nervous system;classification;clinical article;clinical feature;computer analysis;copper metabolism;evoked brain stem response;evoked visual response;female;heredity;human;liver;liver biopsy;male;priority journal;school child;visual stimulation;Wilson disease;penicillamine/dt [Drug Therapy],"Satishchandra, P.;Swamy, H. S.",1989,,,0,0,
2747,Variations in the composition of breast milk in Wilson's disease. [German],,article;breast milk;case report;female;heredity;human;Wilson disease;copper;zinc,"Bunke, H.;Cario, W. R.;Schneider, M.",1989,,,0,0,
2748,Hepatology. [French],,hepatitis/dt [Drug Therapy];human;liver cirrhosis/dt [Drug Therapy];review;stone formation/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];alpha2a interferon;colchicine;colestyramine;glyceryl trinitrate;hepatitis B vaccine;hepatitis vaccine/dt [Drug Therapy];interleukin 2/dt [Drug Therapy];lactitol;lactulose;methotrexate;penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];recombinant alpha2a interferon;recombinant alpha2b interferon;somatostatin/dt [Drug Therapy];terlipressin;ursodeoxycholic acid;vidarabine phosphate/dt [Drug Therapy],"Margalith, D.;Gonvers, J. J.;Frei, P. C.;Fasel, J.;Pettavel, J.;Restellini, A.;Guyvot, J.;Bauerfeind, P.;Stadler, P.;Putztaszeri, G.;Frei, A.;Blum, A. L.",1989,,,0,0,
2749,Case reports of patients with hepatolenticular degeneration-Wilson's disease with emphasis on work capacity. [Serbian],"We presented four patients with hepatolenticular degeneration--Wilson or hepatocerebral dystrophy-Wilson-Konovalov by soviet authors. Our cases were nervous variable of this disease or pseudosclerose (Westphal-Strumphell). The first three patients showed rigid--trembling and one trembling form of disease. All, patients were male. We think that it is very important early identification of this disease, to reduce time from acute manifestation to make a diagnosis and to apply appropriate therapy. This time period in our cases lasted from 0 to 4 years. Except use d- penicillamine (to 900 mg/daily) we think that is also very important use the acidum ascorbicum (to 4.5 gr/daily). This acidum shows less consumption of d- penicillamine and has low complication. Recurrent working ability begins with disappearance of neurological phenomenology and with rehabilitation of psychic status. All our patients we examined by ergometric and psychological tests and we obtained in results working ability population. In our experience and from therapeutic results to make this diagnosis does not mean a priori definite working ability.",adult;article;case report;human;male;middle aged;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy];work capacity,"Toncev, J.;Beslin, M.;Jevdic, D.",1989,,,0,0,
2750,A case of Wilson's disease recovering from severe brain damage--special reference to trientine and D-penicillamine therapy. [Japanese],,adolescent;article;case report;female;human;Wilson disease/dt [Drug Therapy];ethylenediamine derivative/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];trientine/ad [Drug Administration];trientine/dt [Drug Therapy],"Ishitsu, T.;Chikazawa, S.",1989,May,,0,0,
2751,Trace metal interactions in vivo: Inorganic cobalt enhances urinary copper excretion without producing an associated zincuresis in rats,"The effects of cobalt chloride on copper and zinc metabolism in male Sprague-Dawley rats were examined. These effects were compared with those of penicillamine, a chelating agent utilized in the therapy of the genetic abnormality of copper metabolism in humans, Wilson's disease. Cobalt elicited an increased (~4-fold) urinary excretion of copper lasting through 72 h following a single cobalt dose. In contrast to the marked increase in urinary zinc excretion produced by penicillamine, cobalt greatly reduced (~75%) zinc output in urine. Tissue copper and zinc concentrations were measured after treatment with cobalt at doses ranging from 12 to 60 mg/kg body weight. Substantially reduced (~25%) renal copper concentration was observed at 1 and 3 d after cobalt administration. In addition, cobalt produced a concurrent dose-dependent elevation (up to 1.6-fold) in hepatic zinc concentration. Cytosolic zinc was eluted from a Sephadex G-75 column in the molecular weight region associated with metallothionein. Time-dependent induction of metallothionein concentration (10-fold) in liver by cobalt was confirmed by the cadmium/hemoglobin affinity assay. The ability of inorganic cobalt to elevate zinc concentration in liver and produce increased urinary copper excretion without the zincuresis that normally accompanies penicillamine administration represents a newly defined biological property of this essential trace metal.",animal experiment;intraperitoneal drug administration;male;nonhuman;oral drug administration;priority journal;rat;subcutaneous drug administration;urinalysis;Wilson disease;cobalt chloride/pd [Pharmacology];copper;metallothionein;penicillamine/pd [Pharmacology];zinc,"Rosenberg, D. W.;Kappas, A.",1989,,,0,0,
2752,Diagnosis and therapy of Wilson's disease. [German],,hemolytic anemia;human;Parkinson disease;review;thrombocytopenia;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;penicillamine;trientine;zinc,"Niederau, C.;Stremmel, W.;Strohmeyer, G.",1989,,,0,0,
2753,Two and half years of oral zinc sulphate therapy in an adult patient with Wilson's disease,,case report;conference paper;copper blood level;copper excretion;copper metabolism;female;human;oral drug administration;Wilson disease/dt [Drug Therapy];zinc blood level;zinc metabolism;zinc urine level;penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Pasqualicchio, M.;Milanino, R.;Marrella, M.;Moretti, U.;Tomel leri, G.;Velo, G. P.",1989,,,0,0,
2754,A report on Wilson's disease. Two brother-and-sister pairs from two pedigrees. [Japanese],,case report;cataract/di [Diagnosis];cornea opacity/di [Diagnosis];female;human;male;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Ishida, T.",1989,,,0,0,
2755,Liver diseases and their pharmacotherapy. [German],,cholangitis;hemochromatosis/dt [Drug Therapy];hepatitis A/dt [Drug Therapy];hepatitis B/dt [Drug Therapy];human;liver cirrhosis/dt [Drug Therapy];short survey;Wilson disease/dt [Drug Therapy];alpha interferon/dt [Drug Therapy];azathioprine/dt [Drug Therapy];beriglobin;colestyramine/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];deferoxamine mesylate;hepatitis B vaccine/dt [Drug Therapy];immunoglobulin G/dt [Drug Therapy];penicillamine/dt [Drug Therapy];prednisone/dt [Drug Therapy];recombinant alpha2a interferon;spironolactone/dt [Drug Therapy];unclassified drug,"Poralla, T.",1989,,,0,0,
2756,One year of oral zinc sulphate therapy in a child with Wilson's disease,,abstract report;case report;copper metabolism;human;liver function;male;oral drug administration;school child;Wilson disease/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Marrella, M.;Milanino, R.;Moretti, U.;Deganello, A.;Velo, G. P.",1989,,,0,0,
2757,Long-term care and management of Wilson's disease in the GDR,"Diagnosis, long-term management and family investigation of Wilson's disease are provided by selected clinical institutions in the GDR. From 187 patients detected since 1949, 111 are alive. In spite of the principal effectiveness of penicillamine treatment, confirmed by the disappearance of most of the central nervous system symptoms and successful professional rehabilitation of many patients, insufficient therapeutic discipline, psychosocial disturbances and penicillamine side-effects forcing its substitution by zinc or triethylenetetramine dihydrochloride in 14 cases need our further attention.",long-term management;penicillamine;rehabilitation;Wilson's disease;arthropathy/si [Side Effect];article;bone marrow depression/si [Side Effect];brain disease;central nervous system;German Democratic Republic;hepatic coma/dt [Drug Therapy];hepatic coma/th [Therapy];human;liver failure/dt [Drug Therapy];nephrotoxicity/si [Side Effect];priority journal;proteinuria/si [Side Effect];rash/si [Side Effect];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];ceruloplasmin;copper ion;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Bachmann, H.;Lossner, J.;Kuhn, H. J.;Biesold, D.;Siegemund, R.;Kunath, B.;Willgerodt, H.;Teichmann, B.;Wieczorek, V.;Muhlau, G.;Tinschert, K.;Hitzschke, B.;Lakner, K.;Kallwellis, G.;Schmehl, V.",1989,,,0,1,
2758,Treatment of Wilson's disease with zinc. VII. Protection of the liver from copper toxicity by zinc-induced metallothionein in a rat model,"Patients with Wilson's disease often have a further increase in hepatic copper when given zinc as an initial treatment, although there is no associated clinical deterioration. To better understand this situation an animal model was developed in which copper-loaded rats are treated with zinc administered subcutaneously. In the presence of equal amounts of copper loading in liver, control rats show hepatic damage but zinc-treated rats do not. Zinc-treated rats have much higher levels of hepatic metallothionein. Gel filtration studies reveal that much of the hepatic copper in zinc-treated rats is in this metallothionein fraction, whereas the copper in control animals is primarily associated with fractions of high or low molecular weight. Subcutaneous zinc therapy also induces intestinal, but not brain, metallothionein. We interpret these findings to indicate that zinc therapy protects against copper toxicity in liver by induction of hepatic metallothionein, which sequesters copper in a nontoxic form.",animal experiment;article;liver disease;nonhuman;priority journal;rat;subcutaneous drug administration;Wilson disease;copper;zinc carbonate/dt [Drug Therapy];zinc carbonate/pd [Pharmacology],"Lee, D. Y.;Brewer, G. J.;Wang, Y.",1989,,,0,0,
2759,Zinc sulphate in the treatment of Wilson's disease. Presentation of two cases. [Serbian],,adult;case report;heredity;human;oral drug administration;thrombocytopenia/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Kazic, S.;Brmbolic, B.;Dapcevic, B.;Vukcevic, V.;Bojic, P.;Suvakovic, V.;Nikolic, P.",1989,,,0,0,
2760,Can Wilson's disease patients be decoppered?,,letter;nonhuman;priority journal;Wilson disease;penicillamine/cm [Drug Comparison];tetrathiomolybdic acid/cm [Drug Comparison];trientine/cm [Drug Comparison],"Mason, J.;McQuaid, A.;Pheiffer, H.",1989,,,0,0,
2761,Effect of chelators on copper metabolism and copper pools in mouse hepatocytes,"Disorders of copper storage are usually treated by chelation therapy. It is generally thought that the chelators act by mobilizing copper from the liver, hence allowing excretion in the urine. This paper has examined the effect of chelators on copper uptake and storage in mouse hepatocytes. Penicillamine, a clinically important chelator, does not block the uptake of copper or remove copper from hepatocytes. Two other copper chelators, sar and diamsar, which from very stable and kinetically inert Cu<sup>2+</sup> complexes by encapsulating the metal ion in an organic cage, were shown to block copper accumulation by the cells and to remove up to 80% of cell-associated copper. They also removed most (~ 80%) of the <sup>64</sup>Cu accumulated by the cells in 30 min, but released only a small percentage (< 20%) of that accumulated over 18 h. The results show that copper in the hepatocyte can be divided into at least two pools, an easily accessible one, and another, not removable even after long-term incubation with any of the chelators. Most of the copper normally found in the cell appeared to be associated with the former pool.","animal cell;controlled study;female;liver;liver cell;mouse;nonhuman;priority journal;Wilson disease;1,8 diamino 3,6,10,13,16,19 hexaazabicyclo[6.6.6]icosane/cm [Drug Comparison];1,8 diamino 3,6,10,13,16,19 hexaazabicyclo[6.6.6]icosane/do [Drug Dose];1,8 diamino 3,6,10,13,16,19 hexaazabicyclo[6.6.6]icosane/pd [Pharmacology];copper;penicillamine/cm [Drug Comparison];penicillamine/do [Drug Dose];penicillamine/pd [Pharmacology];radioisotope;sar/cm [Drug Comparison];sar/do [Drug Dose];sar/pd [Pharmacology];unclassified drug","McArdle, H. J.;Gross, S. M.;Creaser, I.;Sargeson, A. M.;Danks, D. M.",1989,,,0,0,
2762,Dermal alterations in patients with Wilson's disease treated with D-penicillamine,,heredity;human;human cell;skin defect/si [Side Effect];ultrastructure;Wilson disease/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Pasquali Ronchetti, I.;Quaglino Jr, D.;Baccarani Contri, M.;Hayek, J.;Galassi, G.",1989,,,0,0,
2763,Characteristics of visceral manifestations of Wilson-Konovalov disease. [Russian],,adult;article;case report;differential diagnosis;female;hepatitis/di [Diagnosis];human;jaundice/di [Diagnosis];male;middle aged;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];prednisolone/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Vakharlovskii, V. G.;Verovaia, A. V.",1989,,,0,0,
2764,"Penicillamine dermatopathy with lymphangiectases. A clinical, immunohistologic, and ultrastructural study","The term penicillamine dermatopathy refers to the characteristic hemorrhagic skin lesions found in persons receiving long-term penicillamine therapy for either Wilson's disease or cystinuria. These lesions are thought to develop as a result of faulty collagen and elastin synthesis. We describe a patient with Wilson's disease who developed extensive penicillamine dermatopathy. In addition, histologic, immunochemical, and ultrastructural studies revealed multiple lymphangiectases with blood vessel to lymphatic anastomosis within these lesions, a finding not previously reported. The possible relationship to defective collagen and elastin formation are considered.",adult;bleeding/si [Side Effect];case report;histochemistry;histology;human;lymphangiectasis/si [Side Effect];male;priority journal;ultrastructure;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Goldstein, J. B.;McNutt, N. S.;Hambrick Jr, G. W.;Hsu, A.",1989,,http://dx.doi.org/10.1001/archderm.125.1.92,0,0,
2765,A case of Wilson's disease who developed status epilepticus during D-penicillamine therapy. [Japanese],,adolescent;article;brain cortex;case report;chemically induced disorder;epileptic state;female;human;pathology;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Yoshida, K.;Maruyama, K.;Hashimoto, T.;Shindo, M.;Shoji, S.;Yanagisawa, N.",1989,Jan,,0,0,
2766,Wilson's disease: a report of 4 cases. Follow-up study of a patient for 33 years. [Portuguese],Wilson's disease is a rare disorder with relatively few studies about long term evolutional aspects. The aim was to relate 4 cases emphasizing their polymorphic clinical and laboratorial aspects and the evolutional study of one of them for 33 years and whose treatment enabled the disappearance of the symptoms and the signals of the disease.,adolescent;adult;article;case report;human;liver;liver cirrhosis/et [Etiology];male;metabolism;nervous system;neurologic disease/et [Etiology];psychological aspect;Wilson disease;copper;penicillamine/dt [Drug Therapy],"Chehter, L.;Mincis, M.;Magalhaes, M. B.;Vieira Filho, J. P.;Ferraz, H. B.",1989,1989,,0,0,
2767,Wilson's disease. Hepatic manifestations. [Portuguese],,human;liver;metabolism;pathophysiology;review;urine;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Oliveira e Silva, A.;Roldan Molina, L. F.;dos Santos, T. E.;Santo, G. C.;Gama-Rodrigues, J. J.;D'Albuquerque, L. A.",1989,1989,,0,0,
2768,Wilson's disease: Symptomatic treatment of neuropsychiatric disturbances. Some comments,"Neuropsychiatric disturbances in Wilson's disease may require symptomatic relief beyond often lengthy anticopper treatment. The concomitance of brain and liver damage make it necessary to choose drugs with care, their dosage and the identification of these symptoms due to copper accumulation in the brain and those to hepatic encephalopathy. Short halflife benzodiazepines, 'non classical' neuroleptics, anticholinergics and phenobarbital can be valuable therapeutical tools in symptomatic treatment of Wilson's disease. Wilson's disease is a rare condition characterized by degenerative changes in the brain, with softening of the basal ganglia, and cirrhosis of the liver. Biliary excretion of copper is defective and the metal accumulates in the liver, brain and other tissues. Patients usually present in the second or third decade of life with hepatic, neurologic and psychiatric involvement. the administration of agents that remove copper from the body, penicillamine, or prevent its absorption, zinc, or possible have both actions such, as trientine, at least improve or reverse, the manifestations of most established Wilson's disease, even after months or years, and prevent its appearance in asymptomatic affected siblings. The anticopper therapy of wilson's disease has been xhaustively reviewed (Walshe, 1986; Brewer et al., 1987; Hogenraad et al., 1987; Marsden, 1987; Walshe, 1988). However, besides specific anticopper therapy, in severe cases, particularly in those patients whose clinical clinical picture worsens on the initiation of penicillamine treatment (Brewer et al., 1987) symptomatic treatment may be used and selection of the proper treatment may be awkward in presence of brain damage concomitant with liver involvement. In this paper we will discuss the advisability of symptomatic treatment and, in some cases, indicate the drug of choice.",alcoholism;epilepsy;human;liver disease;neurologic disease;psychiatry;psychological aspect;review;Wilson disease/dt [Drug Therapy];anticonvulsive agent;lithium;lorazepam;neuroleptic agent;oxazepam;penicillamine/dt [Drug Therapy];propranolol;temazepam,"Priori, A.;Formica, A.;Berardelli, A.",1989,,,0,0,
2769,D-Penicillamine pharmacokinetics and pharmacodynamics in man,"Pharmacokinetic studies have provided reasonable definition of the range and extent of PSH's metabolic transformations in humans. The activity of PSH in cystinuria and in hepatolenticular degeneration is largely explained by these transformations. The action of PSH in PSS may also be due to thiazolidine formation, a recognized biochemical reaction of PSH. However, the pharmacodynamics of PSH in suppressing inflammatory activity in RA and, possibly, PSS remain poorly understood. Future studies need to be performed in systems which adequately model PSH-responsive inflammatory disease and which are exposed to therapeutically-relevant concentrations of PSh and its metabolites. Improved understanding of the pharmacodynamics of PSH should lead to safer, more effective use of the drug and indicate a direction for development of new antirheumatic drugs.",chelation;cystinuria;drug therapy;human;pharmacodynamics;pharmacokinetics;priority journal;review;rheumatoid arthritis/dt [Drug Therapy];systemic sclerosis;penicillamine/dt [Drug Therapy];penicillamine/pk [Pharmacokinetics];penicillamine/pd [Pharmacology],"Joyce, D. A.",1989,,,0,0,
2770,Indications for liver transplantation in fulminant Wilson's disease. [German],"In two 19-year-old girls with Wilson's disease the condition took a fulminant course, including a poor general state, marked haemolysis and ascites. In the first patient the diagnosis was histologically confirmed only after three weeks, and onset of treatment with penicillamine was therefore delayed. With this medication the concentrations of alkaline phosphatase, cholinesterase and total bilirubin returned to normal, but again became abnormal after about seven weeks. Despite substitution of clotting factors thromboplastin time remained reduced. She died 82 days after the onset of symptoms. In the second patient, treatment with penicillamine was started at once, without waiting for histological confirmation. All laboratory values became normal and remained so. It is concluded from these observations that liver transplantation is indicated if the abnormal values for cholinesterase, thromboplastin time and bilirubin do not remain normal after six weeks and if the initial suppression of alkaline phosphatase continues or occurs again.",adult;female;human;liver transplantation;priority journal;Wilson disease/di [Diagnosis];Wilson disease/su [Surgery];bilirubin;cholinesterase;penicillamine/dt [Drug Therapy];thromboplastin,"Zilker Th, R.;Felgenhauer, N.;Hibler, A.;von Clarmann, M.",1989,,,0,0,
2771,ABC of clinical genetics: Treatment of genetic disorders,,acute intermittent porphyria;carboxylase deficiency;congenital adrenal hyperplasia;congenital hypothyroidism;Crigler Najjar syndrome;diet therapy;Duchenne muscular dystrophy;enzyme deficiency;galactosemia;gene therapy;genetic disorder/dt [Drug Therapy];genetic disorder/su [Surgery];genetic disorder/th [Therapy];glucose 6 phosphate dehydrogenase deficiency;heredity;homocystinuria;human;hyperuricemia;methylmalonic aciduria;myotonic dystrophy;phenylketonuria;porphyria;porphyria cutanea tarda;priority journal;pseudocholinesterase deficiency;short survey;Wilson disease;aldosterone/dt [Drug Therapy];allopurinol/dt [Drug Therapy];anticonvulsive agent/ae [Adverse Drug Reaction];barbituric acid derivative/ae [Adverse Drug Reaction];biotin/dt [Drug Therapy];cyanocobalamin/dt [Drug Therapy];dapsone/ae [Adverse Drug Reaction];estrogen/ae [Adverse Drug Reaction];hydrocortisone/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];primaquine/ae [Adverse Drug Reaction];probenecid/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];sulfonamide/ae [Adverse Drug Reaction];suxamethonium/ae [Adverse Drug Reaction];thyroxine/dt [Drug Therapy],"Kingston, H. M.",1989,,,0,0,
2772,Diagnosis and treatment of metabolic liver diseases. [German],,hemochromatosis/dt [Drug Therapy];human;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];deferoxamine/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Stremmel, W.;Niederau, C.;Strohmeyer, G.",1989,,,0,0,
2773,Deterioration of Wilson's disease following the start of penicillamine therapy,,human;letter;priority journal;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology],"Pall, H. S.;Williams, A. C.;Blake, D. R.;Brewer, G. J.;Yuzbasiyan-Gurkan, V.",1989,,,0,0,
2774,Orthotopic liver transplantation in Wilson's disease with acute liver failure. [German],"Liver histology demonstrated progressive cirrhosis in a 19-year-old girl with a subacute form of Wilson's disease. Despite D-penicillamine administration her liver functions rapidly deteriorated further. Orthotopic liver transplantation was performed. Postoperatively there were two mild rejection episodes, an organic psychiatric syndrome and generalized tremor. Copper metabolism and clinical symptoms became normal postoperatively. Five months after the transplantation she was in a good general condition, able to continue her education.",adult;case report;female;hematuria/si [Side Effect];heredity;human;immunosuppressive treatment;liver failure/th [Therapy];liver transplantation;proteinuria/si [Side Effect];Wilson disease/cn [Congenital Disorder];cyclosporin/cb [Drug Combination];cyclosporin/dt [Drug Therapy];methylprednisolone/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];prednisolone/cb [Drug Combination];prednisolone/dt [Drug Therapy],"Kreuzpaintner, G.;Lauchart, W.;Frenzel, H.;Stremmel, W.;Berges, W.;Pichlmayr, R.;Strohmeyer, G.",1988,,,0,0,
2775,Topography of P300 in neuropsychiatric pharmaco therapy - cognitive P300-fields in an organic psychosyndrome (Wilson's disease) before and during treatment with D-Penicillamin. [German],Beside senile dementia of Alzheimer's type (SDAT) there are also dementive syndromes due to a disturbance in metabolism. In a case with a disturbance of copper metabolism (Wilson's disease) a similar P300-pattern was found as described in SDAT with signs of a frontal amplitude elevation. Under therapy with d-penicillamine the frontal P300-positivity moved from frontal to parietal structures. Combined with this migration was an amelioration in cognitive function. This single-case study underlines the significance of P300-topography in the evaluation of therapy effects in dementive disorders.,adult;case report;cognition;dementia;human;male;organic psychosyndrome/di [Diagnosis];organic psychosyndrome/dt [Drug Therapy];p300 wave;psychological aspect;Wilson disease;penicillamine/dt [Drug Therapy],"Maurer, K.;Dierks, Th",1988,,,0,0,
2776,Control of therapeutic prevention of copper accumulation in the liver in Wilson's disease by means of <sup>64</sup>Cu. [German],,case report;heredity;human;methodology;oral drug administration;Wilson disease;copper 64;penicillamine/dt [Drug Therapy];radioisotope;zinc sulfate/dt [Drug Therapy],"Gunther, K.;Siegemund, R.;Lossner, J.;Kuhn, H. J.",1988,,,0,0,
2777,Fibrinolytic activity in patients with hepatolenticular degeneration: Influence of penicillamine. [Serbian],,clinical article;fibrinolysis;human;prothrombin time;Wilson disease/dt [Drug Therapy];fibrinogen;penicillamine/dt [Drug Therapy],"Babic, T.;Relja, M.",1988,,,0,0,
2778,Protean manifestation of Wilson's disease: A review of seven Saudi patients,,clinical article;extrapyramidal syndrome;family study;heredity;histology;human;human cell;liver cirrhosis;oral drug administration;Saudi Arabia;Wilson disease;penicillamine/dt [Drug Therapy],"Bahemuka, M.;Karrar, Z. A.;Al Mofleh, I.;Bahakim, H.;Hafeez, M. A.",1988,,,0,0,
2779,The treatment and diagnosis of Wilson's disease,,human;oral drug administration;pregnancy;psychological aspect;short survey;teratogenicity/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy];zinc sulfate/pd [Pharmacology],"Brewer, G. J.;Yuzbasiyan-Gurkan, V. A.;Young, A. B.",1988,,,0,0,
2780,Wilson's disease: Evolutive study of 13 cases. [Spanish],,adolescent;adult;child;clinical article;clinical feature;female;follow up;human;male;systemic lupus erythematosus/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Pineda, J. R.;Garrido, A.;Albillos, A.;Pascual, M. L.;Llagostera, F.;Leal, J. C.;Escartin, P.",1988,,,0,0,
2781,Treatment of Wilson's disease with Zincteral. [Polish],"In 27 patients with reliably diagnosed Wilson's disease treated previously with penicillamine (Cuprenil, Polfa) for from 10 months to 12 years penicillamine was withdrawn due to various adverse effects and replaced with zinc sulphate (Polish preparation Zincteral) in doses of 200 mg 4 times daily for 12 months. The neurological status was improved in 6 cases. No adverse effects of zinc sulphate were observed.",adult;article;female;human;male;metabolism;middle aged;Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;sulfate/dt [Drug Therapy];sulfate/pk [Pharmacokinetics];zinc/dt [Drug Therapy];zinc/pk [Pharmacokinetics];zinc sulfate,"Kuczynska-Zardzewialy, A.;Rodo, M.;Czlonkowska, A.",1988,1988,,0,0,
2782,Diagnosis of a case of Wilson's disease by cytochemical staining of fine needle aspirates of the liver,,case report;copper blood level;cytochemistry;cytology;female;histochemistry;human;human cell;letter;needle biopsy;school child;staining;Wilson disease/di [Diagnosis];alanine aminotransferase;aspartate aminotransferase;ceruloplasmin;copper;immunoglobulin A;lactate dehydrogenase;penicillamine/dt [Drug Therapy],"Kobayashi, T. K.;Nukina, S.;Nishida, K. I.;Sawaragi, I.",1988,,,0,0,
2783,Current aspects of D-penicillamine and pregnancy. [German],"Although the outcome of most pregnancies is normal under D-penicillamine a teratogenic effect of the drug is known from animal studies. A few cases of children with birth defects whose mothers received D-penicillamine during pregnancy are reported in the literature. Whether D-penicillamine therapy should be performed throughout pregnancy or whether it should be interrupted depends on the disease to be treated. While in patients with morbus Wilson, continuous treatment with D-penicillamine is justified, it is advisable to interrupt the therapy during pregnancy in patients with rheumatoid arthritis.",congenital malformation/et [Etiology];cystinuria/dt [Drug Therapy];female;human;newborn;pregnancy;pregnancy complication/dt [Drug Therapy];review;rheumatoid arthritis/dt [Drug Therapy];risk factor;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Miehle, W.",1988,,,0,0,
2784,Penicillamine-induced pseudo-pseudoxanthoma elasticum in a patient with rheumatoid arthritis,"Penicillamine is a heavy metal chelator which is used in the treatment of Wilson's disease, cystinuria, rheumatoid arthritis and scleroderma. The cutaneous side-effects of prolonged, high dose (1-2 g/day) treatment include skin fragility, elastosis perforans serpiginosa (EPS), cutis laxa and rarely pseudoxanthoma elasticum-like changes. We describe the clinical and post-mortem findings in a patient who developed pseudo-pseudoxanthoma elasticum and multi-system penicillamine-induced elastosis while taking D-penicillamine (750 mg/day). There are no previous reports of penicillamine-induced elastic tissue damage in a patient with rheumatoid arthritis.",adult;case report;elastosis;fatality;female;human;priority journal;pseudoxanthoma elasticum/si [Side Effect];rheumatoid arthritis/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Burge, S.;Ryan, T.",1988,,http://dx.doi.org/10.1111/j.1365-2230.1988.tb00693.x,0,0,
2785,Wilson's disease: reflections about an alternative therapy with oral zinc. [Italian],,case report;human;oral drug administration;Wilson disease/dt [Drug Therapy];zinc/dt [Drug Therapy],"Bragetti, P.;Rufini, S.;Castellucci, G.;Morucci, P.",1988,,,0,0,
2786,Evaluation of hepatic reserve in patients with Wilson's disease treated with D-penicillamine. Capacity for antipyrine oxidation and urinary excretion of its major metabolites. [Japanese],,clinical article;human;liver cirrhosis;liver function;oxidation;urinary excretion;Wilson disease;penicillamine;phenazone,"Ito, N.;Kawata, S.;Noda, S.;Imai, Y.;Saitoh, R.;Tamura, S.;Inada, M.;Inui, Y.;Matsuda, Y.;Nagase, T.;Tarui, S.",1988,,,0,0,
2787,"Striational autoantibodies: Quantitative detection by enzyme immunoassay in myasthenia gravis, thymoma, and recipients of D-penicillamine or allogeneic bone marrow","Striational autoantibodies (StrAb) are a useful serologic marker of thymoma in patients with myasthenia gravis (MG). We compared a standard immunofluorescence method with a new enzyme immunoassay (EIA) for detection of StrAb. Retrospective testing of 264 stored sera by the two methods yielded well-correlated results (58 sera were positive by both assays; r = 0.8). For 104 patients with spontaneously acquired MG or thymoma, results were 100% concordant, of which 53% were positive. For 34 recipients of D-penicillamine, StrAb were found in 15% by EIA and in 6% by immunofluorescence. StrAb were detected in two of four bone marrow recipients by EIA and in one by immunofluorescence. Prospective testing of 434 fresh sera (of which 49 were positive by the two methods) yielded discordant results in only 4. Serial EIA quantitation of StrAb in two patients with MG and thymoma proved useful in monitoring immunosuppressant therapy and in a third patient predicted recurrence of the tumor. A high prevalence of StrAb was detected by both assays in elderly patients with spontaneous MG, but StrAb were more readily quantifiable by EIA. The EIA method proved to be highly sensitive and specific for detecting StrAb in patients with thymoma with and without MG, in patients treated with D-penicillamine, and in those with graft-versus-host disease after bone marrow transplantation.",graft versus host reaction/di [Diagnosis];heredity;human;muscle;myasthenia gravis/di [Diagnosis];review;rheumatoid arthritis/di [Diagnosis];thymoma/di [Diagnosis];Wilson disease/di [Diagnosis];autoantibody;penicillamine/dt [Drug Therapy],"Cikes, N.;Momoi, M. Y.;Williams, C. L.;Howard Jr, F. M.;Hoagland, H. C.;Whittingham, S.;Lennon, V. A.",1988,,,0,0,
2788,Efficiency of zinc sulphate in the treatment of Wilson's disease. [Polish],,case report;drug efficacy;drug tolerance;human;oral drug administration;Wilson disease/dt [Drug Therapy];penicillamine;zinc sulfate/dt [Drug Therapy],"Jonderko, G.;Pluta, H.;Wieczorek, U.",1988,,,0,0,
2789,Recent experience and problems in long-term care of patients with Wilson's disease in the GDR. [German],,clinical article;copper metabolism;heredity;human;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Bachman, H.;Lossner, J.;Biesold, D.;Kunath, B.;Willgerodt, H.;Siegemund, R.",1988,,,0,0,
2790,Wilson's disease and epilepsy,"The relationship between Wilson's disease and epilepsy is explored, both in the literature and in a series of 200 cases of Wilson's disease. Details of 44 literature and 14 personal cases of both disorders are presented. The prevalence on December 1, 1986 of epilepsy in the Cambridge series was 6.2%, ten times higher than that of epilepsy in the general population. Seizures in Wilson's disease occur at any stage of the disease, but often begin shortly after the start of treatment. Prognosis of seizures was comparable with the best quoted figures for idiopathic epilepsy: at 7 years 60% of cases had been seizure-free for at least 5 years, and 75% for at least 2 years. Possible mechanisms of seizures are discussed. Penicillamine-induced pyridoxine deficiency is probably not involved in more than a minority of cases. It is more likely that a direct effect of copper deposition is responsible for most of the seizures.",adolescent;adult;clinical article;electroencephalography;epilepsy/di [Diagnosis];epilepsy/dt [Drug Therapy];epilepsy/et [Etiology];female;human;male;oral drug administration;priority journal;short survey;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine;phenobarbital/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Dening, T. R.;Berrios, G. E.;Walshe, J. M.",1988,,,0,0,
2791,Clinical significance of penicillamine antibodies,,antibody production;antibody response;human;immune complex nephritis;letter;priority journal;side effect;Wilson disease/dt [Drug Therapy];immunoglobulin G;immunoglobulin M;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Storch, W. B.",1988,,,0,0,
2792,The efficacy of oral zinc therapy as an alternative to penicillamine for Wilson's disease,,human;letter;priority journal;Wilson disease/cn [Congenital Disorder];Wilson disease/th [Therapy];penicillamine;zinc/dt [Drug Therapy],"Cossack, Z. T.;Scheinberg, I. H.;Sternlieb, I.",1988,,,0,0,
2793,Vitamin B<inf>6</inf>-deficiency under D-penicillamin in case of M. Wilson. [German],,adult;clinical article;female;human;male;oral drug administration;pyridoxine deficiency/di [Diagnosis];Wilson disease/dt [Drug Therapy];aspartate aminotransferase;penicillamine/cb [Drug Combination];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];pyridoxine/cb [Drug Combination];pyridoxine/dt [Drug Therapy];tiopronin/cb [Drug Combination];tiopronin/cm [Drug Comparison];tiopronin/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc sulfate/cb [Drug Combination];zinc sulfate/cm [Drug Comparison];zinc sulfate/dt [Drug Therapy],"Kuhn, H. J.;Lossner, J.",1988,,,0,0,
2794,Removal of essential metalloelements by hemodialysis and exchange transfusion in a patient with acute hepatic necrosis from Wilson's disease,,case report;chelation therapy;exchange blood transfusion;hemodialysis;human;intravenous drug administration;liver necrosis;Wilson disease/th [Therapy];copper;edetic acid/dt [Drug Therapy];iron;zinc,"Arnold, W. C.;Butler, H. L.;Kearns, G. L.;Sorenson, J. R. J.",1988,,,0,0,
2795,Wilson's disease and chronic active hepatitis. [Spanish],,adult;case report;female;hepatitis/di [Diagnosis];hepatitis/dt [Drug Therapy];human;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Cutrin Prieto, C.;Gude Sampedro, E.;Casal Iglesias, L.;Lado Lado, E.;Carballo Hernandez, C.;Rodriguez Lopez, I.;Barrio Gomez, E.",1988,,,0,0,
2796,Effect of D-penicillamine treatment on brain metabolism in Wilson's disease: A case study,"Sequential measurements of brain glucose metabolism were carried out in a patient with Wilson's disease, before and after successful treatment with D-penicillamine. They demonstrate an evolution of regional metabolism consistent with clinical improvement. The first study showed marked hypometabolism in the putamen on both sides. The second analysis showed bilateral improvement, with predominant residual deficits in the right putamen, while clinical symptoms of striatal dysfunction persisted on the left side. This observation suggests that positron emission tomography is able to follow the neurological evolution in cases of Wilson's disease.",adult;case report;female;glucose metabolism;human;positron emission tomography;priority journal;putamen;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy];radioisotope,"De Volder, A.;Sindic, C. J. M.;Goffinet, A. M.",1988,,,0,0,
2797,"A disorder with low serum copper level, dementia, dysarthria, gait disturbance and involuntary movements. [Japanese]",,adult;case report;copper blood level;dementia;dysarthria;gait disorder;heredity;human;involuntary movement;male;Menkes syndrome;oral drug administration;Wilson disease;ceruloplasmin;penicillamine/dt [Drug Therapy],"Ono, S.;Kurisaki, H.;Kamakura, K.",1988,,,0,0,
2798,Reversal of severe neurological manifestations of Wilson's disease following orthotopic liver transplantation,"Experience with liver transplantation for patients with Wilson's disease who have major neurological impairments is limited, and this report describes the results obtained in two such patients. The first was a 30-year-old man with a 14-month history of hepatic and neurological impairment. In spite of treatment with d-penicillamine, he developed increasing dysarthria, dysphagia, akinesia and rigidity of all four limbs, and required continuous nursing care. Following transplantation, liver function was almost normal from four weeks onwards, but recovery of neurlogical function was much slower and was not seen until two to three months after surgery. By four months he was sufficiently mobile to be discharged, and when he returned for assessment at eight months, no abnormal neurological signs were detectable. The second patient was a 27-year-old woman with worsening liver dysfunction for eight years; one year previously she had developed dysarthria, akinesia, a fine tremor and moderate rigidity of all limbs as well as marked psychological impairment. There was no improvement on treatment with d-penicillamine or trientine, but as liver function returned to normal two months after liver grafting, her neurological and psychological function began to improve so that by three months she could be discharged.",adult;akinesia;case report;congenital disorder;copper blood level;dysarthria;dysphagia;esophagus;human;liver;liver transplantation;nervous system;neurologic disease;priority journal;rigidity;therapy;tremor;Wilson disease;penicillamine;trientine,"Polson, R. J.;Rolles, K.;Calne, R. Y.",1987,,,0,0,
2799,Wilsons disease. A study of 12 cases,,case report;controlled study;human;liver;preliminary communication;therapy;Wilson disease;penicillamine;zinc sulfate,"Joshi, R. M.;Kagalwala, T. Y.;Bharucha, B. A.",1987,,,0,0,
2800,On the proof of antibodies against D-penicillamine. III. Detection of circulating antibodies against D-penicillamine in patients with Wilson's disease treated with D-penicillamine. Preliminary results. [German],,adverse drug reaction;blood and hemopoietic system;clinical article;diagnosis;drug analysis;drug blood level;drug identification;etiology;human;immunofluorescence;therapy;dextro penicillamine antibody;penicillamine;unclassified drug,"Trautmann, B.;Storch, W.",1986,,,0,0,
2801,D-penicillamine and collagen. [French],,central nervous system;drug indication;drug therapy;etiology;human;joint;lathyrism;liver;lung fibrosis;oral drug administration;priority journal;respiratory system;review;rheumatoid arthritis;therapy;Wilson disease;collagen;penicillamine,"Camus, J. P.;Koeger, A. C.",1986,,,0,0,
2802,EEG investigations of Wilson's disease. [Czech],,central nervous system;clinical article;diagnosis;drug metabolism;drug therapy;family;heredity;heterozygote;human;therapy;penicillamine,"Nevsimalova, S.;Marecek, Z.;Roth, B.",1986,,,0,0,
2803,Treatment of portosystemic encephalopathy by zinc supplementation. [French],"Three patients with alcoholic cirrhosis and acute encephalopathy (IInd stage) consecutive to digestive hemorrhage were rapidly improved by giving SO4Zn per os; but other measures had been taken. A fourth patient (IIIrd stage) recovered in 7 hours with intravenous injection of Zn, without any other therapy, excepting what was needed to reestablish volemia and control plasma and platelet coagulation. There is in cirrhosis a deep depletion in Zn; zincemia is commonly half the normal, with usually slight symptoms of Zn-deficiency. Ingestion of alcohol, hemorrhage, stress and the ensuing catabolism cause an acute loss inducing encephalopathy, the symptoms of which are closely similar to those observed in deep Zn depletion. When Zn is given, alterations in the protein metabolism may be corrected, and most probably, Zn has a direct impact on the nervous tissue. But the characteristic alteration in the brain is not a diminution of the Zn concentration, but an increase in copper, which allows to question our knowledge on Wilson's disease.",case report;central nervous system;hepatic encephalopathy;human;liver;liver cirrhosis;therapy;zinc,"Couinaud, C.",1985,,,0,0,
2804,Brain stem damage in acute form of Wilson's disease. [Polish],,autopsy;brain stem;case report;central nervous system;histology;histopathology;human;human cell;Wilson disease;copper;penicillamine,"Kida, E.;Renkawek, K.;Smialek, M.",1985,,,0,0,
2805,Syndrome resembling systemic lupus erythematosus (SLE) induced by penicillamine in a patient with Wilson's disease. [Slovak],,adverse drug reaction;case report;congenital disorder;drug therapy;human;oral drug administration;systemic lupus erythematosus;therapy;Wilson disease;penicillamine,"Kalina, P.;Prochazkova, L.;Hauftova, D.",1985,,,0,0,
2806,Copper removal with zinc. [Dutch],,case report;central nervous system;human;oral drug administration;priority journal;therapy;Wilson disease;copper;penicillamine;zinc;zinc sulfate,"Hoogenraad, T. U.",1985,,,0,0,
2807,Changes in zink metabolism associated with prolonged D-penicillamine therapy for Wilson-Konovalov's disease. [Russian],,adverse drug reaction;asthenia;central nervous system;clinical article;congenital disorder;drug therapy;human;liver;liver cirrhosis;muscle;therapy;Wilson disease;penicillamine;zinc,"Mzhelskaya, T. I.;Gotovtseva, E. V.",1984,,,0,0,
2808,Release of endogenous Zn<sup>2+</sup> from brain tissue during activity,"The role of divalent transition metal ions in neural function is poorly understood. In excess, these ions are associated with neurological disorders such as Wilson's disease, Pick's disease and epileptic seizures. We suggest that zinc ions, which are contained in nerve terminals, are extruded into the extracellular space during neuronal activity. Excessive levels of zinc may be released during intense neuronal activation, and contribute to the paroxysm and toxic damage observed. Zinc ions are contained in high concentrations in mossy fibres of the hippocampal formation, and it is the postsynaptic neurones of these fibres which are most susceptible for the toxic effects of kainic acid, a potent convulsant, or to chronic exposure to organometallic compounds. Here we demonstrate for the first time that Zn<sup>2+</sup> is released into the extracellular space during excitation of hippocampal slices.",animal cell;brain;central nervous system;extracellular space;hippocampus;nerve ending;nervous system;nonhuman;rat;zinc,"Assaf, S. Y.;Chung, S. H.",1984,,,0,0,
2809,Reduced binding of <sup>3</sup>H-spiroperidol to lymphocyte in Wilson's disease,"Biochemical studies of CSF from patients with Wilson's disease (WD) have increased that alterations in the state of dopaminergic and serotoninergic systems are similar to those manifested in Parkinson's disease. Recently, the density of dopaminergic receptors on lymphocytes has been found to be diminished in Parkinson's disease. In the present study, <sup>3</sup>H-spiroperidol binding was evaluated in lymphocytes acquired from 12 patients suffering from WD, as compared to blood donors. A significant decrease in the number of binding sites (B(max)) was observed in the lymphocytes of the WD patients. There was no clear relationship between clinical status, age and duration of the disease and the alterations in receptor density. The mechanism underlying the decrease in lymphocyte <sup>3</sup>H-spiroperidol binding sites in WD demands clarification.",clinical article;drug binding;drug receptor binding;human;lymphatic system;nervous system;pharmacokinetics;Wilson disease;ceruloplasmin;cupric chloride cu 64;dopamine receptor;lymphocyte receptor;penicillamine;radioisotope;spiperone;spiperone h 3;unclassified drug,"Czlonkowski, A.",1984,,,0,0,
2810,Cutaneous lesions during treatment with penicillamine and penicillamine-derivatives. [French],,adverse drug reaction;congenital disorder;human;intoxication;joint;pemphigus vulgaris;rheumatoid arthritis;serpiginous elastoma;short survey;skin defect;skin toxicity;therapy;Wilson disease;amoxicillin;ampicillin;azathioprine;cyclophosphamide;penicillamine;penicillin derivative;penicillin G;prednisone;pyritinol;tiopronin,"Venencie, P. Y.;Morel, P.",1984,,,0,0,
2811,Methods in laboratory investigation. Electron probe X-ray analysis on human hepatocellular lysosomes with copper deposits: Copper binding to a thiol-protein in lysosomes,"Livers of eight patients wth chronic liver diseases were investigated by energy dispersive x-ray analysis. First, three kinds of preparations (osmium-Epon sections, glutaraldehyde-frozen sections, and unfixed-frozen sections) were compared for element detectability at a subcellular level. The glutaraldehyde-frozen sections were satisfactory as far as copper, sulfur, and phosphorus were concerned. Five patients (one patient with Wilson's disease, one chronic cholestasis, one chronic hepatitis, and two asymptomatic primary biliary cirrhosis) yielded x-ray images of copper and sulfur consistent with hepatocellular lysosomes. Second, the glutaraldehyde-frozen sections were utilized for a study of copper deposits in the patients' livers. There was a significant correlation between copper and sulfur contents in the lysosomes of all patients studied but no correlation in the remainder of the cytoplasm. Zinc was not detected in the lysosomes. Whatever the content of copper in the lysosomes, the ratio of DELTAcopper to phosphorus (weight/weight) to DELTAsulfur to phosphorus was 0.60. These data indicate that most lysosomal copper binds to a thiol protein, probably metallothionein, in the liver.",biliary cirrhosis;chronic hepatitis;diagnosis;human;liver;lysosome;major clinical study;methodology;priority journal;Wilson disease;X ray analysis;copper;thiol,"Hanaichi, T.;Kidokoro, R.;Hayashi, H.;Sakamoto, N.",1984,,,0,0,
2812,Treatment of Wilson's disease. [German],,human;letter;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];sulfate/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc sulfate,"Hoogenraad, T. U.;van Hattum, J.",1987,5 Jun,,0,0,
2813,Penicillamin-induced pemphigus. [German],"D-Penicillamin is effective in the treatment of Wilson's disease, cystinuria and rheumatoid arthritis. However, it may have adverse side-effects by inducing a spectrum of diseases such as myasthenia gravis, lupus-like disease, IgA deficiency and pemphigus vulgaris. A case of D-penicillamin-induced pemphigus is presented. The clinical aspects, pathogenesis, immunology and therapy of D-penicillamin-induced diseases are discussed.",adult;adverse drug reaction;case report;cytology;diagnosis;drug eruption;etiology;histology;human;intoxication;joint;pathogenesis;pemphigus vulgaris;priority journal;rheumatoid arthritis;skin toxicity;penicillamine,"Kind, P.;Goerz, G.;Gleichmann, E.;Plewig, G.",1987,,,0,0,
2814,Inborn errors of trace metal metabolism,,central nervous system;child;childhood;congenital disorder;human;inborn error of metabolism;Menkes syndrome;short survey;therapy;Wilson disease;copper;trace metal;zinc,"Aggett, P. J.",1987,,,0,0,
2815,Pathogenesis of cerebral disorders in hepatocerebral dystrophy. [Russian],"On the basis of data obtained in the course of long-term observation of more than 60 patients with hepatocerebral dystrophy and analysis of the literature the authors consider the problems related to the pathogenesis of cerebral disorders in this disease. It has been found that the underlying mechanisms of the disorder is chronic intoxication of the central nervous system which is induced by the glut of ""non-ceruloplasmin"" copper and brings about a cascade of secondary metabolic disturbances, including defect of the amino acid pool in the blood plasma, zinc deficit, and disorders of redox processes. The possible role of each of these disorders has been considered in the pathogenesis of cerebral disturbances associated with hepatocerebral dystrophy.","article;blood;brain;brain level;chemistry;human;liver;metabolism;oxidation reduction reaction;pathology;pathophysiology;Wilson disease/et [Etiology];agents interacting with transmitter, hormone or drug receptors;amino acid;copper/an [Drug Analysis];zinc","Lekar, P. G.;Makarova, V. A.;Botvinnik, V. S.",1987,,,0,0,
2816,New possibilities in the treatment of Wilson-Konovalov disease (hepatolenticular degeneration). [Bulgarian],"The favourable therapeutic effect of a new copper chelator--trientine (triethylenetetramine dihydrochloride) is reported. The drug was applied to 3 patients, 18 to 25 years of age, with Wilson-Konovalov disease (hepatolenticular degeneration) who in the course of chronic D-penicillamine treatment developed drug intolerance with signs of nephrotoxicity (in one patient) and myelotoxicity with leucopenia and thrombocytopenia (in two patients). The treatment was carried out orally with optimal daily dose of 1.8 gr trientine which led to a 4-6 times increase of the 24 hour urine copper excretion. The drug is well tolerated and no side effects of allergic reactions have been registered up to now in the patients treated.",adolescent;adult;article;case report;comparative study;drug screening;drug tolerance;female;human;pathophysiology;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];trientine/ae [Adverse Drug Reaction];trientine/ad [Drug Administration],"Kolarski, V.",1987,,,0,0,
2817,Hepatolenticular degeneration. Apropos of 102 cases. [Portuguese],"The author reports the clinical and laboratory findings in 102 patients of hepatolenticular degeneration (HLD) followed up in the Department of Neurology, University of Sao Paulo Medical School, since 1946. The problem of the early diagnosis of the relatives is analysed, the pathology of Wilson's disease is reviewed, and the relationship of HLD with other hepatocerebral diseases is examined. Etiopathogenesis is discussed according to current researches, the role of the decreased biliary copper excretion being emphasized. The results of treatment with D-penicillamine in 84 cases are commented.",female;human;male;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Canelas, H. M.",1987,Jun,,0,0,
2818,Sequential laparoscopic and ultrasonographic observations of the liver in a case of Wilson's disease treated with D-penicillamine. [Japanese],,adult;case report;echography;human;laparoscopy;liver nodule/di [Diagnosis];liver nodule/dt [Drug Therapy];liver nodule/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Ohnishi, S.;Aoyama, H.;Shirataki, H.;Ishikawa, T.;Matsuhashi, N.;Moriyama, T.;Aburatani, H.;Imawari, M.;Takaku, F.",1987,,,0,0,
2819,D-penicillamine-induced myasthenia gravis and Wilson's disease: A clinical case. [Japanese],,adverse drug reaction;case report;central nervous system;drug therapy;human;muscle;myasthenia gravis;oral drug administration;pregnancy;therapy;Wilson disease;penicillamine;pyridostigmine,"Koya, N.;Sasamoto, A.;Tateno, A.",1987,,,0,0,
2820,Kinetics of copper absorption in zinc-overload states and following the withdrawal of zinc supplement: The role of endogenous zinc status,"Zinc (Zn), in therapeutic dosages, has been used to inhibit copper (Cu) absorption in patients with Wilson's disease. A series of experiments were conducted to substantiate the effects of high dosages of Zn on Cu absorption using the experimental animal model. In the first experiment, five groups of mice were fed five different levels of Zn: 6 ppm (basal diet), 30 ppm (control), 750 ppm, 1,000 ppm, and 2,400 ppm, for a period of 35 days. <sup>64</sup>Cu-loading test was conducted to measure whole body retention (WBR) of <sup>64</sup>Cu at the 10th, 14th, 21st, and 35th day. Results showed that the inhibition of <sup>64</sup>Cu absorption by Zn is dose- and time-dependent. However, maximum inhibition occurred in mice fed 1,000 ppm of Zn, and no additional effect was observed in mice fed 2,400 ppm of Zn. In the second experiment, the distribution between the gastrointestinal tract (GIT) and gut-free carcass, of the retained dose of <sup>64</sup>Cu, was measured in controls and in the group fed 750 ppm of Zn. While WBR of <sup>64</sup>Cu was significantly lower (p < 0.01) in mice fed 750 ppm of Zn, the distribution of the retained dose was not affected. In the third experiment, a group of mice was fed 30 ppm of Zn for a period of 70 days (control), and a second group was fed 1,000 ppm of Zn for the first 35 days (repletion), after which they were switched to the basal diet (6 ppm) for the following 35 days (depletion). WBR of <sup>64</sup>Cu was conducted in intervals throughout the experimental period. Endogenous fecal Zn (MFZn) was determined at the end of repletion (0 t), and at intervals during depletion. Results from this experiment indicated that the effect of Zn on <sup>64</sup>Cu absorption continued for up to 21-35 days, following the withdrawal of Zn supplement. In addition, WBR of <sup>64</sup>Cu correlated significantly (r = -0.92, p < 0.005) with MFZn. We conclude that (a) high doses of Zn may not cause a complete inhibition of Cu absorption, and (b) endogenous Zn secreted into the GIT (as MFZn) plays a major role in inhibiting Cu absorption and, thus, the maintenance of high endogenous Zn status is essential for maximal inhibition of Cu absorption.",animal model;drug absorption;intestine absorption;intravenous drug administration;mouse;nonhuman;pharmacokinetics;priority journal;small intestine;Wilson disease;copper;radioisotope;zinc,"Cossack, Z. T.;Van den Hamer, C. J. A.",1987,,,0,0,
2821,A simple and convenient preparation of triethylene tetramine dihydrochloride (trien) for the treatment of Wilson's disease and its stability. [Japanese],,drug activity;drug stability;methodology;wettability;Wilson disease;trientine/pr [Pharmaceutics],"Suzuki, T.;Sasabuchi, K.;Sato, E.;Unno, K.",1987,,,0,0,
2822,Westphal-Strumpell disease: Description of a clinical case. [Italian],"A case of hepatolenticular degeneration with the clinical pattern of Westphal-Strumpell disease is described. Diagnosis was based on clinical pattern, absence of hepatic impairment, typical biochemical abnormalities of copper metabolism and response (clinical and biochemical) to D-penicillamine.",case report;human;periodic paralysis;ceruloplasmin;copper;penicillamine,"Nuccetelli, F.;Assetta, M.;Colangelo, U.;Gambi, D.",1987,,,0,0,
2823,Penicillamine,"D-Penicillamine (2-amino-3-mercapto-3-methylbutanoic acid) is a trifunctional thiol amino acid. It is widely used for the treatment of a variety of diseases including rheumatoid arthritis, Wilson's disease, cystinura, heavy metal poisoning, chronic active hepatitis, and primary biliary cirrhosis. The determination of D-penicillamine in biological fluids of patients being treated with this drug is complicated by the fact that D-penicillamine occurs in many different forms; free thiol, internal disulfied, the mixed disulfide with cysteine, the metabolite S-methyl-D-penicillamine, and D-penicillamine bound to plasma proteins may all be present in blood and urine samples. Assay methods employing high-performance liquid chromatography (HPLC), gas-liquid chromatography, amino acid analysis, colorimetry, and radioimmunoassay have been described.",drug analysis;human cell;penicillamine,"Wolf-Heuss, E. M.",1987,,,0,0,
2824,"Clinico-diagnostic, therapeutic and prognostic studies of Wilson-Konovalov disease. The results of 25 years' experience. [Bulgarian]","The author's 25 years experience in clinical, diagnostic, therapeutic and prognostic study of 24 patients with Wilson-Konovalov's disease (hepatilenticular degeneration) is presented. The great diagnostic importance of copper metabolism (plasma copper level, urine copper), plasma ceruloplasmin concentration, histochemical and quantitative determination of copper in liver cells (after a liver biopsy) is pointed out. These are of special importance in young patients (under 25 years) and in children with chronic parenchymal liver disease. In 1/4 of the patients the early stage of the disease resembled chronic active hepatitis (predominantly liver type of the disease). The basic therapeutic drug is D-penicillamine hydrochloride and when it is not tolerated the drug Trien may be used. Very good therapeutic results and considerable improvement of prognosis, social and working rehabilitation of the patients have been achieved. The preconditions for good therapeutic and prognostic results are the early discovery, exact diagnosis and prolonged purposeful pathogenetic treatment (chelatory and hepatoprotective). Zinc sulfate and potassium sulfide are only secondary therapeutic means in patients with hepatolenticular degeneration.",adolescent;adult;article;child;chronic disease;chronic hepatitis/di [Diagnosis];differential diagnosis;female;human;male;methodology;mortality;multimodality cancer therapy;prognosis;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy],"Kolarski, V.",1987,,,0,0,
2825,Trientin in Wilson's disease. Therapeutic possibilities in patients who cannot tolerate penicillamine. [Norwegian],,adult;article;case report;drug hypersensitivity;human;immunology;male;Wilson disease/dt [Drug Therapy];ethylenediamine derivative/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];trientine/dt [Drug Therapy],"Ritland, S.",1987,10 Aug,,0,0,
2826,Systemic lupus erythematosus induced by d-penicillamine in Wilson's disease: apropos of a case. [Spanish],,adult;article;case report;chemically induced disorder;human;male;systemic lupus erythematosus;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Lopez-Guerra, N.;Alvarez Lario, B.;Garcia-Monco, C.;Pena Sagredo, J. L.",1987,4 Apr,,0,0,
2827,Trientine - An orphan drug for the treatment of Wilson's disease,,adverse drug reaction;blood and hemopoietic system;clinical article;copper blood level;copper urine level;drug comparison;drug efficacy;drug tolerance;human;short survey;therapy;urinary tract;Wilson disease;penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];trientine/do [Drug Dose],"Fromtling, R. A.",1987,,,0,0,
2828,Management of Wilson's disease with zinc sulphate - Experience in a series of 27 patients,"Evaluation of the literature concerning the various approaches for the treatment of Wilson's disease led to the conclusion that zinc sulphate might be a good choice because it is effective and relatively safe. Twenty seven patients were managed with zinc sulphate for a total period of 142 patients-years. The drug was administered in doses varying from 300 to 1200 mg/day. Of the 9 patients who were treated with zinc from the start, 8 improved and one died from severe cirrhosis. All 8 patients who were placed on zinc after intolerance to penicillamine did well on zinc therapy. Ten patients were changed to zinc after they had first been treated with penicillamine without developing signs of intolerance. Of this group 8 patients were kept on long-term zinc therapy, 2 were changed back to penicillamine because of personal preference. Signs of intolerance to zinc were not observed. All patients kept a diet containing about 1.2 mg of copper a day. Our experience supports the idea that zinc sulphate is a good choice for the treatment of Wilson's disease: the drug is effective, safe and cheap.",blood and hemopoietic system;diet;drug efficacy;drug indication;drug safety;drug therapy;human;liver;major clinical study;oral drug administration;priority journal;therapy;Wilson disease;copper;penicillamine;zinc sulfate,"Hoogenraad, T. U.;Van Hattum, J.;Van den Hamer, C. J. A.",1987,,,0,0,
2829,Treatment of Wilson's disease: In D-penicillamine we trust - What about zinc?,,diagnosis;drug efficacy;drug indication;drug therapy;heredity;human;liver;oral drug administration;priority journal;short survey;therapy;treatment;Wilson disease;dimercaprol;penicillamine;trientine;zinc;zinc acetate;zinc sulfate,"Lipsky, M. A.;Gollan, J. L.",1987,,http://dx.doi.org/10.1002/hep.1840070331,0,0,
2830,Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens,"The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance.",central nervous system;clinical article;drug therapy;human;oral drug administration;priority journal;therapy;treatment;Wilson disease;copper;penicillamine;zinc;zinc acetate,"Hill, G. M.;Brewer, G. J.;Prasad, A. S.",1987,,http://dx.doi.org/10.1002/hep.1840070318,0,0,
2831,Laparoscopic findings before and after the D-penicillamine therapy in a case of Wilson's disease. [Japanese],,adolescent;case report;color;congenital disorder;diagnosis;drug therapy;human;laparoscopy;liver;liver cirrhosis;liver nodule;therapy;Wilson disease;penicillamine,"Sugiura, K.;Hirata, R.;Yosida, S.",1987,,,0,0,
2832,Clinico-biochemical diagnosis of Wilson's disease and its therapy. [Slovak],"The presented review paper deals with the current knowledge in pathophysiology, clinico-biochemical (CB) diagnosis and therapy of Wilson's disease (W.d.). CB screening is done by the determination of ceruloplasmin and total copper in serum, copper in urine under basic conditions and after penicillamine administration. Second stage screening, in case of diagnostic uncertainty (as well as post mortem), is done by quantitative determination of copper in bioptic liver samples, or by the <sup>64</sup>Cu load test. This fatal inborn disease has for over 30 years been treated effectively with penicillamine and in case of its intolerance with triethylentetramine hydrochloride. The most recent therapy with zinc has a different mechanism of action - it eliminates the excess of copper from the organism via feces, whereas the former treatments by urine. For monitoring the therapy of W.d. the authors recommend to adjust the dosage according to urine copper excretion or the <sup>64</sup>Cu load test. The therapy is checked up once a year - unless the clinical condition of the patient calls for a shorter interval - by determining urinary copper excretion on 2-3 consecutive days and by testing tubular functions. Hemogram, ALT and urinalysis are to be examined along with clinical check up at least 4 times a year. In case of zinc therapy serum zinc is to be monitored. Concluding the authors suggest groups indicated for CB screening of W.d., which is not as rare as it used to be considered (today 1:35000 or 1:50000): 1) Patients with suspected hepatologic or neurologic symptomatology from 5 to 60 year of age. 2) First degree relatives of the patient with W.d. 3) Children with chronic liver symptomatology or acute symptomatology with an anusual long-lasting or fulminant course. In children even a slot lamp is to be used in searching for the Kayser-Fleischer ring. Screening for W.d. and therapy monitoring is done: 1) by a clinician alone observing strictly specimen collection requirements, 2) by a clinician in cooperation with a medical specialist in clinical biochemistry, 3) by a CB metabolic outpatient department in cooperation with a clinician.",clinical article;human;liver;serum;urine;Wilson disease;copper;penicillamine/pd [Pharmacology],"Slugenova, E.",1987,,,0,0,
2833,Vitamin-resistant rickets preceding Wilson's disease. [French],,article;case report;child;female;human;hypophosphatemia/dt [Drug Therapy];hypophosphatemia/et [Etiology];Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ergocalciferol/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Zaimi, I.;Khiari, A.;Ben Dridi, M. F.;Maherzi, H.;Ben Osman, R.",1986,May,,0,0,
2834,Absorption of zinc investigated; may inhibit copper uptake,,drug absorption;drug antagonism;editorial;human;intestine absorption;oral drug administration;pharmacokinetics;small intestine;Wilson disease;copper;glucose;zinc;zinc acetate,Anonymous,1986,,,0,0,
2835,Liver cirrhosis: Is pharmacotherapy of the underlying disease possible?. [German],Cirrhosis of the liver has many causes and the answer to the question: ''is drug treatment of cirrhosis useful?'' depends on the underlying cause and not on histology. The answer is definitely ''yes'' in the inherited disorders like Wilson's disease or haemochromatosis in which specific treatment is highly successful. In primary biliary cirrhosis drug treatment with corticosteroids is only justified in cases with features of chronic active autoimmune hepatitis (CAH). The results with penicillamine appear disappointing. Azathioprine may be of value in some cases. Colchicine and cyclosporine are on trial and results are not yet available. The HB(s)AG negative autoimmune CAH-cirrhosis should be treated with corticosteroids or with a combination of corticosteroids and azathioprine for months or even years. Steroids are no longer recommended for HB(s)AG positive patients with CAH-cirrhosis because the results of controlled trials suggest that they may even be harmful: replication of virus is enhanced and the tendency to cancer formation may be increased. The results of treatment with antiviral drugs alone or combined with interferon are still scarce and more will have to be evaluated before any recommendations can be given. In alcoholic liver disease drug treatment is rarely successful. Glucocorticosteroids have been tried and may be indicated in rare and exceptional cases with encephalopathy. Propylthiouracil and colchicine are presently in use in controlled trials; conclusive evidence is still lacking whether androgenic hormones are useful in the treatment of alcoholic cirrhosis.,bile duct;drug therapy;etiology;hemochromatosis;human;liver;liver cirrhosis;oral drug administration;primary biliary cirrhosis;priority journal;short survey;therapy;Wilson disease;azathioprine;chlorambucil;colchicine;colestyramine;cyclosporin A;deferoxamine;deferoxamine mesylate;glucocorticoid;ossopan;oxandrolone;penicillamine;propylthiouracil,"Martini, G. A.",1986,,,0,0,
2836,Elastase 1 levels during oral zinc therapy,,adverse drug reaction;diagnosis;drug blood level;drug efficacy;drug therapy;editorial;human;liver;oral drug administration;pancreas;priority journal;therapy;Wilson disease;penicillamine;zinc,"Umeki, S.;Konishi, Y.;Yasuda, T.",1986,,,0,0,
2837,The Kayser-Fleischer ring during long-term treatment in Wilson's disease (hepatolenticular degeneration). A follow-up study,"The role of Kayser-Fleischer rings is described in 67 patients with Wilson's disease, both in the asymptomatic and symptomatic stage of the disease during life-long therapy, which lasted up to 22 years. The rings were missing in 60% of patients in the presymptomatic stage and in 2% of those in the symptomatic stage at the time of diagnosis. The Kayser-Fleischer rings disappeared in 81% of the patients (completely in 41% and incompletely in 59%). In 2 of the 6 asymptomatic patients the rings did not reabsorb even after therapy of more than 10 years. The fading of Kayser-Fleischer rings seems to be independent not only of the stage of the disease but also of the effectiveness of the decopperizing treatment.",autosomal recessive inheritance;clinical article;cornea;diagnosis;drug efficacy;drug therapy;heredity;human;kayser fleischer ring;liver;oral drug administration;priority journal;therapy;visual system;Wilson disease;penicillamine;trientine;zinc sulfate,"Lossner, A.;Lossner, J.;Bachmann, H.;Zotter, J.",1986,,,0,0,
2838,Treatment of hepatologic affections: Advance in 1985. [German],"The following three observations were of particular interest in 1985: 1. Isolated liver metastases of colonic cancer can be successfully treated with partial hepatic resection. 2. Many centers across Europe have reported good results with liver transplantations. 3. Lactitol, a disaccharide for the treatment of hepatic encephalopathy, has been marketed in Switzerland. The following therapeutic aspects are also interesting: benign stenosis of the bile ducts can be dilated endoscopically. The use of sclerotherapy in bleeding esophageal varices has been critically examined. Oral administration of zinc is a useful alternative in Wilson's disease when d-penicillamin produces side-effects. Cyanidanol was withdrawn from the market. Intensive attempts were made to produce an effective synthetic vaccine for the prevention of hepatitis B.",bile duct;bile duct obstruction;central nervous system;colon cancer;drug indication;drug therapy;endoscopic sclerotherapy;esophagus;esophagus varices;hepatic encephalopathy;hepatitis;hepatitis B;human;intravenous drug administration;large intestine;liver;liver metastasis;liver resection;oral drug administration;priority journal;review;sclerotherapy;therapy;Wilson disease;aciclovir;albendazole;azathioprine;catechin;colchicine;cyclosporin A;flubendazole;hepatitis B vaccine;interferon;lactitol;mebendazole;methylprednisolone;padma 28;penicillamine;prednisolone;prednisone;propranolol;ranitidine;rowachol;somatostatin;spironolactone;terfenadine;terlipressin;unclassified drug;unithiol;ursodeoxycholic acid;vasopressin;vidarabine;vidarabine phosphate;zinc sulfate,"Wegmann, D.;Guyot, J.;Cilluffo, T.",1986,,,0,0,
2839,Fulminant Wilson's disease treated with postdilution hemofiltration and orthotopic liver transplantation,"A 22-yr-old woman presented with fulminant Wilson's disease. The diagnosis was suspected clinically and was later confirmed with chemical and pathologic studies. She presented with acute hepatic failure, hemolysis, and acute anuric renal failure. Postdilution hemofiltration and continuous arteriovenous hemofiltration with oral D-penicillamine allowed removal of a total of 95,700 mug of copper; 78,665 mug of the total were removed via postdilution hemofiltration alone. On the 57th day, the patient received successful liver and renal transplants. We found that the determination of serum copper was instrumental in the diagnosis of fulminant Wilson's disease, that postdilution hemofiltration allowed a rapid removal of copper in the presence of renal failure, and that, finally, orthotopic liver transplantation should be performed early in the clinical course of these patients. This patient is the longest survivor of this serious condition.",case report;diagnosis;hemofiltration;human;kidney;kidney failure;kidney transplantation;liver;liver failure;liver transplantation;priority journal;serum;therapy;Wilson disease;copper;penicillamine,"Rakela, J.;Kurtz, S. B.;McCarthy, J. T.",1986,,,0,0,
2840,Triethylene tetramine in Wilson's disease. [Hebrew],,adverse drug reaction;case report;central nervous system;congenital disorder;copper excretion;drug comparison;drug therapy;fever;human;intoxication;liver;nervous system;neurotoxicity;oral drug administration;rash;skin toxicity;therapy;Wilson disease;penicillamine;trientine,"Rave, D.;Vengrover, D.;Kleinman, J.;Leitersdorf, E.",1986,,,0,0,
2841,Wilson's disease and liver failure in childhood,"The clinical and biochemical findings in two siblings with Wilson's disease are reported. One of the siblings, an 11-year-old girl, developed acute liver failure terminating in death within a few weeks. Prior to her terminal illness she had been in good health with no symptoms suggestive of Wilson's disease. Copper content of urine, liver, kidney and brain was increased to 10-300 times upper normal. The liver revealed extensive micronodular cirrhosis with nonbile pigment deposits. An elder brother, fifteen years old, revealed abnormal liver function tests with urine copper excretion increased to 20 times upper normal. Treatment with penicillamine was started. Following a short period of deterioration his condition has since been steadily improving.",adolescent;case report;child;childhood;congenital disorder;diagnosis;human;liver;liver failure;priority journal;school child;therapy;urine;visual system;Wilson disease;copper;penicillamine,"Sagen, E.;Lange, O.;Westgaard, G.",1986,,,0,0,
2842,The treatment of Wilson's disease in paediatrics: Oral zinc therapy versus penicillamine,"In the present investigation we studied the balance of copper in 2 sets of children with Wilson's disease. The first set of patients were treated with oral zinc as the sole treatment since early diagnosis. The second set consisted of patients who were treated with only penicillamine since early diagnosis. Copper balance was also conducted on normal healthy volunteers, for comparison.",central nervous system;child;clinical article;drug comparison;drug therapy;genetics;heredity;human;liver;oral drug administration;priority journal;therapy;Wilson disease;ceruloplasmin;copper;penicillamine;zinc;zinc sulfate,"Cossack, C. T.;Bouquet, J.",1986,,,0,1,
2843,Wilson's disease: Clinical presentation and use of prognostic index,"As the results of treatment in Wilson's disease are so dependent on the stage at which penicillamine therapy is started, the antecedant history in 34 patients with Wilson's disease was analysed with particular respect to the earliest manifestations of the disease. Lethargy and anorexia (70%) jaundice (50%) and abdominal pain (48%) were the commonest symptoms and less common were intellectual deterioration (22%) and recurrent epistaxes (22%). The duration of symptoms before diagnosis ranged from five days to three years (mean 10.5 months) and in only five of the patients was the diagnosis established before referral. Analysis of the physical signs at presentation showed hepatomegaly (81%) and splenomegaly (70%) to be common and the only signs which were significantly more common in the 13 fatal cases were jaundice and ascites. In three of these and in one other patient who survived the clinical course was exceptionally severe and was indistinguishable from fulminant hepatic failure. Based on the severity of abnormality of serum aspartate aminotransferase, bilirubin, and prothrombin time on admission a prognostic index was derived which enabled complete separation of fatal and non-fatal cases and when subsequently used in a further nine index cases correctly predicted the outcome. Two further cases found to have indices in the fatal category did well after liver transplantation, which needs to be considered as soon as the diagnosis is established in cases with such severe liver damage.",diagnosis;histology;human;liver;liver failure;liver transplantation;major clinical study;priority journal;prognosis;symptom;Wilson disease;aminotransferase;ceruloplasmin;copper;penicillamine,"Nazer, H.;Ede, R. J.;Mowat, A. P.;Williams, R.",1986,,,0,0,
2844,A case of Wilson's disease associated with hemolytic anemia,,blood and hemopoietic system;case report;hemolytic anemia;hereditary spherocytosis;heredity;human;preliminary communication;school child;therapy;Wilson disease;penicillamine,"Hayakawa, T.;Okuda, A.;Kim, K. M.",1986,,,0,0,
2845,Effect of oral ZnSO4 on urine copper and blood trace elements in 60 patients with Wilson's disease. [Chinese],,adolescent;adult;article;blood;child;female;human;male;metabolism;urine;Wilson disease/dt [Drug Therapy];copper;sulfate/dt [Drug Therapy];trace element;zinc/dt [Drug Therapy];zinc sulfate,"Yang, R. M.",1986,Apr,,0,0,
2846,D-penicillamine and cutaneous lesions in Wilson's disease. [Spanish],,case report;chemically induced disorder;drug eruption/et [Etiology];human;letter;male;suicide attempt;sweat gland disease;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity],"Peiro Grasa, A.;Barnadas Andinach, M.;Moreno Carazo, A.;Grau-Veciana, J. M.",1986,1986,,0,0,
2847,Analysis of D-penicillamine by gas chromatography utilizing nitrogen-phosphorus detection,"A method is presented for the analysis of the 'orphan' drug D-penicillamine (D-Pa), which is used for the treatment of the inherited rare copper metabolism dysfunction known as Wilson's disease, by assaying a derivative of the compound by gas chromatography employing a rubidium sensitized nitrogen-phosphorus detector. Analytical procedures are described for the analysis of residues of D-Pa . HCl salt in animal feed and for the analyses of the salt or free base from aqueous solutions by utilizing a single-step double derivatization with diazomethane-acetone. Stability data for D-Pa . HCl in animal feed and for the free base in water are presented. An ancillary fluorescence derivatization procedure for the analysis of D-Pa in water is also reported.",drug analysis;drug determination;gas chromatography;methodology;nonhuman;priority journal;theoretical study;Wilson disease;copper;penicillamine,"Rushing, L. G.;Hansen Jr, E. B.;Thompson Jr, H. C.",1985,,,0,0,
2848,Primary hepatocellular carcinoma associated with Wilson's disease in a young woman,A 27 year old woman with hepato-lenticular degeneration (Wilson's disease) was found to have primary hepatocellular carcinoma (PHC) three and a half years after she was started on treatment with D-penicillamine. The tumour was resected since when she has remained well. Her liver function tests were normal throughout the course of her disease. The available literature is reviewed and possible mechanisms for this association proposed.,case report;diagnosis;histology;human;liver;liver cell carcinoma;priority journal;therapy;Wilson disease;penicillamine,"Guan, R.;Oon, C. J.;Wong, P. K.",1985,,,0,0,
2849,Zinc-copper-lead interactions,,clinical article;human;priority journal;therapy;Wilson disease;copper;lead;metallothionein;zinc,"Brewer, G. J.;Hill, G. M.;Dick, R. D.",1985,,,0,0,
2850,Hemolytic anemia and Wilson's disease. [Spanish],,blood and hemopoietic system;case report;diagnosis;hemolytic anemia;human;liver;liver failure;therapy;Wilson disease;penicillamine,"Suquia, B.;Martin, M. I.;Querol, R.",1985,,,0,0,
2851,Therapeutic orphans,,central nervous system;economic aspect;human;legal aspect;liver;priority journal;therapy;Wilson disease;penicillamine;zinc sulfate,Anonymous,1985,,,0,0,
2852,Reversible inhibition of specific <sup>3</sup>H-spiroperidol binding by heavy metal ions in rat striatum,"Four divalent heavy metals interact with neural membranes from rat striatum in vitro to inhibit ligand binding of dopamine receptors as labelled by <sup>3</sup>H-spiroperidol, a dopamine antagonist. Their relative inhibitory potencies in decreasing order are as follows: copper > lead > cadmium > mercury. Copper exhibited an IC<inf>50</inf> value of 6.7 x 10<sup>-6</sup> M is the most potent in competing with 2.5 x 10<sup>-8</sup> M <sup>3</sup>H-spiroperidol for receptor binding. Equilibrium binding constants computed from Scatchard analysis of results show that copper reduces the density as well as the affinity of the receptors in binding the ligand. Partial reactivation of dopamine receptors from copper inhibition is achieved by adding the chelating agent d-penicillamine, but not diethylenetriaminepentaacetic acid (DTPA). The relevance of these findings is discussed in relation to the clinical symptoms of Wilson's disease and abnormal copper accumulation in basal ganglia secondary to chronic liver disease.",animal cell;animal model;basal ganglion;central nervous system;corpus striatum;drug administration;drug comparison;drug inhibition;drug mechanism;drug receptor binding;nonhuman;pharmacokinetics;preliminary communication;priority journal;rat;Wilson disease;cadmium;cadmium chloride;copper;copper sulfate;cupric chloride;dopamine;dopamine receptor;ferrous chloride;haloperidol;lead;lead nitrate;mercuric nitrate;mercury;penicillamine;pentetic acid;radioisotope;spiperone h 3;unclassified drug,"Wong, Y. W.;Chiu, S.;Mishra, R. K.",1985,,,0,0,
2853,Unithiol in Wilson's disease,,adverse drug reaction;congenital disorder;drug comparison;drug efficacy;drug indication;drug mechanism;drug therapy;editorial;human;liver;oral drug administration;priority journal;therapy;dimercaprol;penicillamine;unithiol;zinc sulfate,"Hoogenraad, T. U.;Van Hattum, J.;Walshe, J. M.",1985,,,0,0,
2854,Studies on the content of trace elements in the hair of patients with Wilson's disease and healthy individuals. [Chinese],,adolescent;adult;article;child;female;hair/an [Drug Analysis];human;infant;male;metabolism;middle aged;preschool child;spectrometry;Wilson disease;copper/an [Drug Analysis];proton;trace element/an [Drug Analysis];zinc/an [Drug Analysis],"Zhang, Z. X.;Feng, Y. K.;Liu, G. D.;Sun, G. Q.;Wang, S. Z.;Sha, Y.;Liu, P. S.;Zhang, R. H.",1985,Aug,,0,0,
2855,New therapeutic possibilities for the elimination of copper in the case of Wilson's disease (hepatocerebral degeneration). [German],,clinical article;human;liver;therapy;Wilson disease;copper;penicillamine;trientine;zinc sulfate,"Lossner, J.;Zotter, J.;Kuhn, H. J.",1985,,,0,0,
2856,Elastosis perforans serpiginosa and pseudoxanthoma elasticum-like skin change due to D-penicillamine,"High dose D-penicillamine is used in the therapy of Wilson's disease and cystinuria. Elastosis perforans serpiginosa, penicillamine dermopathy, cutis hyperelastica, excessive skin wrinkling and pseudoxanthoma elasticum-like side change have all been documented as developing in consequence of such therapy. We report a patient in whom mild pseudoxanthoma elasticum-like change and elastosis perforans serpiginosa developed, following high dose D-penicillamine treatment for cystinuria.",adverse drug reaction;case report;congenital disorder;cystinuria;drug eruption;drug therapy;elastosis perforans serpiginosa;human;intoxication;oral drug administration;priority journal;pseudoxanthoma elasticum;school child;skin toxicity;therapy;penicillamine,"Meyrick Thomas, R. H.;Kirby, J. D. T.",1985,,http://dx.doi.org/10.1111/j.1365-2230.1985.tb00588.x,0,0,
2857,Wilson's disease: Assessment of D-penicillamine treatment,"Serum copper and zinc concentrations and 24 hour urinary coppoer and zinc excretion were determined serially from the beginning of treatment with D-penicillamine in four children with Wilson's disease. The data show a progressive decrease in both serum copper and zinc concentrations in all. Urinary copper excretion gradually levelled off to approximately 50% of initial values, but zinc excretion increased. Urinary zinc:copper ratios therefore increased with the duration of treatment. Copper elimination was considered adequate as soon as challenge with a test dose of D-penicillamine did not result in an increase in copper excretion. Urinary zinc excretion was increased further by the test dose. Zinc depletion was suspected clinically in one patient on D-penicillamine maintenance treatment. Lowering the dose alleviated the symptoms, urinary zinc loss decreased from 64 to 34 mumol/24 hours, and copper excretion remained largely unchanged. Data obtained indicate that D-penicillamine alters the metabolism of both copper and zinc. The extent of this is not only dose dependent but is also related to the efficacy of copper elimination. Both copper and zinc concentrations must by monitored to assess the benefits of treatment and the risks of inducing manifest or subclinical zinc deficiency.",case report;child;drug therapy;human;liver;nervous system;priority journal;serum;therapy;urinary excretion;Wilson disease;ceruloplasmin;copper;penicillamine;zinc,"Van Caillie-Bertrand, M.;Degenhart, J. J.;Luijendijk, I.",1985,,,0,0,
2858,Oral zinc sulphate for Wilson's disease,"After initial promotion of copper excretion with D-penicillamine, the effect of oral zinc sulphate (3 x 150 mg/day, loading dose; 3 x 100 mg/day, maintenance dose) in two children with clinically stable Wilson's disease was evaluated after completion of three years' treatment. The course, judged by clinical, biochemical, and histological parameters was satisfactory in both. The urinary copper concentration reverted to less than 1.26 mumol/24 hours; and the serum copper concentration decreased further during zinc sulphate treatment. In one child the rise in 24 hour urinary copper excretion observed after a challenge dose of D-penicillamine (+/- 20 mg/kg) remained constant throughout the period of observation while the liver copper content fell from 1460 mug/g dry weight to 890 mug/g dry weight. In the other patient, however, the liver copper content as well as the 24 hour urinary copper excretion increased after D-penicillamine challenge during the third year of treatment. We conclude that zinc sulphate is a low toxic and well tolerated alternative for D-penicillamine. The dosage depends, however, on individual factors not yet well understood, and we recommend restriction of its use to patients who do not tolerate D-penicillamine well. We suggest monitoring of treatment with yearly D-penicillamine challenge and a liver biopsy if liver function deteriorates.",case report;child;diagnosis;drug efficacy;drug therapy;human;liver;liver biopsy;liver function;nervous system;oral drug administration;priority journal;serum;therapy;urinary excretion;Wilson disease;copper;penicillamine;zinc sulfate,"Van Caillie-Bertrand, M.;Degenhart, H. J.;Visser, H. K. A.",1985,,,0,1,
2859,Wilson's hepatolenticular degeneration. Apropos of a case report. [French],,adult;article;case report;female;human;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/an [Drug Analysis];penicillamine/dt [Drug Therapy],"Ducasse, A.;Segal, A.",1985,Jan,,0,0,
2860,<sup>64</sup>Cu uptake of Wilson's disease patients on zinc therapy,,clinical article;congenital disorder;etiology;human;therapy;Wilson disease;copper 64;radioisotope;zinc,"Hill, G. M.;Brewer, G. J.;Juni, J. E.",1985,,,0,0,
2861,"Treatment of copper storage disease (Wilson's disease in Bedlington terriers using N,N'-Bis-(2-aminoethyl)-1,3-propane diamine (2,3,2-tetramine)",,"abstract report;animal experiment;animal model;diagnosis;dog;drug blood level;drug efficacy;drug monitoring;drug tissue level;drug urine level;histology;liver;nonhuman;therapy;copper;n,n' bis(2 aminoethyl) 1,3 propanediamine;penicillamine","Hunsaker, H. A.;Twedt, D. C.;Magne, M.;Allen, K. G. D.",1985,,,0,0,
2862,Penicillamine induced cheilosis,,adverse drug reaction;case report;cheilosis;congenital disorder;drug dose;drug therapy;human;oral drug administration;school child;therapy;Wilson disease;penicillamine,"Rajendran, N.;Koteeswaran, A.;Kala, M.",1985,,,0,0,
2863,Long-term follow-up study of seventeen cases with Wilson's disease. [Japanese],"We performed a follow-up study of 17 patients with Wilson's disease (6 men, 11 women) in order to evaluate the effect of penicillamine therapy. All patients have been treated with penicillamine for 1 to 17 years. The severity in the patients were evaluated by using the grading system (Grade 0 to 4) reported by Goldstein et al. Six of 17 patients showed improvement, 6 patients showed no change of severity and 4 patients died in spite of the treatment. One patient has been asymptomatic for 7 years by treatment. An improvement was observed in the group treated with penicillamine more than 600 mg/day, and also the group treated for longer than 5 years. There was no relationship between the severity before treatment and the subsequent effects of treatment. These results suggest that a dosage of penicillamine and the duration of the treatment are important factors of clinical improvement of the patients.",central nervous system;clinical article;drug therapy;heredity;human;nervous system;neurologic disease;oral drug administration;therapy;Wilson disease;penicillamine,"Tanaka, K.;Itoyama, Y.;Tobimatsu, S.",1985,,,0,0,
2864,Teratogenic risk during treatment of Wilson disease. [French],"Untreated Wilson's disease usually causes infertility or abortion, as a result of increased intrauterine copper level. Therefore, a chelation treatment is necessary during the whole pregnancy. The most used is D-Penicillamine whose teratogenic risks such as cutis laxa, dermatopathy or complex mesenchyme abnormalities are paradoxically rare in the new borns of treated Wilson's disease mothers, perhaps owing to hypercupremia that protects the foetus from excessive copper deficiency. Yet, it's wise to reduce chelation treatment about a quarter fold and to add 50 mg vitamin B6 weekly as we did in our case whose child was born normal.",adult;article;case report;congenital malformation/pc [Prevention];drug effect;female;fetus;human;newborn;pregnancy;risk;Wilson disease/th [Therapy];copper/an [Drug Analysis];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];pyridoxine/dt [Drug Therapy],"Piussan, C.;Mathieu, M.",1985,Sep,,0,0,
2865,Interactions of trace elements: Clinical significance,"We examined interaction of the trace element zinc with copper and lead. In sickle cell anemia, the usual situation is one of mild to moderate zinc deficiency owing to renal loss of zinc. Zinc deficiency seems to produce a mild overburden of copper and an increased ceruloplasmin level, probably by enhancing copper absorption. With zinc therapy, this process is reversed. Pharmalogical doses of zinc, when administered in a way to ensure effectiveness (without food) will usually lead to copper deficiency. We have taken advantage of the copper-depleting effect of zinc to design a new therapy for Wilson's disease. Zinc, by inducing intestinal metallothionein, inhibits absorption of copper from food, and inhibits reabsorption of endogenously secreted copper, thereby producing a negative copper balance in Wilson's disease. Once we were certain that zinc blocks acculmulation of copper in the liver of Wilson's disease patients, zinc therapy will be available as one approach for treating this fatal disease. The animal literature indicates that zinc protects against lead toxicity when both elements are given orally, no doubt through the intestinal metallothionein mechanism. In preliminary experiments in rats we have not been able to show that toxicity from lead that arrives into the body through a nonoral route is affected by oral zinc supplements.",blood and hemopoietic system;drug interaction;etiology;human;liver;review;sickle cell anemia;therapy;Wilson disease;ceruloplasmin;copper;lead;trace element;zinc,"Brewer, G. J.;Hill, G.;Dick, R. D.",1985,,,0,0,
2866,Genetic trace metal disturbances,"Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria.",congenital disorder;etiology;genetic disorder;heredity;human;inborn error of metabolism;Menkes syndrome;protein synthesis;short survey;Wilson disease;copper;dna;molybdenum;rna;trace metal;zinc,"Wai-Yee, Chan;Rennert, O. M.",1985,,,0,0,
2867,Migraine headaches and Wilson's disease associated with intrauterine copper contraceptive devices,Individuals who have some disorder of copper metabolism appear to be at increased risk if they use a copper-containing intrauterine contraceptive device or if their diet is high in copper-containing foods. They may not develop the full spectrum of hepatolenticular degeneration but may have more frequent migraine episodes. Foods high in copper are often high in tyramine that is known to induce migraine.,adverse drug reaction;birth control;congenital disorder;headache;human;intrauterine contraceptive device;intravaginal drug administration;migraine;short survey;Wilson disease;adrenergic receptor stimulating agent;copper;copper intrauterine device;manganese;monoamine oxidase inhibitor;penicillamine;tyramine,"Harrison, D. P.",1985,,,0,0,
2868,Oral zinc therapy as long term treatment of Wilson's disease: About a child treated for 4 years. [French],"A 13 year-old boy with Wilson's disease was treated with zinc sulphate per os for 4 years. This treatment, which was effective and non toxic, could subsitute for penicillamine as long term treatment of Wilson's disease.",case report;central nervous system;child;drug therapy;human;liver;priority journal;therapy;Wilson disease;penicillamine;zinc;zinc sulfate,"Alexiou, D.;Hatzis, T.;Koutselinis, A.",1985,,,0,0,
2869,Effects of high-dosage trihexyphenidyl on symptomatic dystonia in a case of Wilson disease. [Japanese],"We report a 16-year-old boy with Wilson disease who relapsed suddenly with generalized dystonia, which was improved by a high dosage of trihexyphenidyl. He was diagnosed as having Wilson disease when he developed a hemolytic crisis at age 6. When he was 14, gait disturbance, dysgraphia and dysarthria appeared. These were improved by an increase in D-penicillamine dosage only. He was well until he deteriorated acutely soon after suffering acute respiratory infection. On admission, he could neither walk, speak nor swallow, and showed violent involuntary movement and right hemiplegia. Hepatic functions, however, were normal. Dystonia and anarthria were persistent, although involuntary movement and hemiplegia gradually improved. Surface EMG showed the characteristic dystonic pattern. A few weeks after treatment with trihexyphenidyl at 10 mg daily was started, he became able to stand, walk and write. When the medication was discontinued to ascertain its effects, he became obviously worse and could hardly walk or write. Psychiatric symptoms including irritability and emotional instability were noticed as adverse effects, but they were not severe enough to stop the medication. Seven months after treatment began, the dystonia tended to fluctuate, increasing in the morning and decreasing in the evening, with no corresponding diurnal changes in homovanillic acid or dopamine levels in the CSF. Fahn (1979) reported that the treatment of dystonia of various types with a high dosage of trihexyphenidyl was especially effective in childhood. In the present case, we too found a beneficial effect with trihexyphenidyl at a dosage of 10-12 mg daily without any severe adverse effects.",adolescent;blood and hemopoietic system;case report;central nervous system;diagnosis;drug dose;drug efficacy;dystonia;electromyography;hemolysis;human;muscle;oral drug administration;priority journal;therapy;Wilson disease;carbamazepine;clonazepam;diazepam;penicillamine;trihexyphenidyl,"Hirabayashi, S.;Kanda, H.;Tsuno, T.",1985,,,0,0,
2870,Determination of triethylenetetramine dihydrochloride in aqueous solution by reversed-phase ion-pairing high performance liquid chromatography and conductivity detection,Triethylenetetramine dihydrochloride (TETA) has been used for the treatment of Wilson's disease which is a metabolic disorder that prevents its victims from eliminating excess copper. TETA was scheduled for toxicological evaluation because of a deficiency of such information. Analytical chemical procedures to determine the purity of the drug as well as the proper concentration and stability of the drug in dosed water were prerequisites for the toxicological tests. A high performance liquid chromatography (HPLC) procedure employing ion-pairing and conductivity detection has been developed for the analysis of TETA in dosed water at levels as low as 10 mug/mL and for the determination of drug purity. The conductivity detector response was linear over the concentration range of 10 to 100 mug/mL. Data are presented concerning the stability of the drug in water during ambient storage and after autoclaving. An ancillary colorimetric procedure for the analysis of aqueous TETA solutions is also presented which is based on measuring the absorbance of the colored TETA copper chelate at 599 nm. The HPLC procedure is applicable to the analysis of TETA and the chemically similar polyamines spermidine and spermine in admixture.,colorimetry;drug analysis;drug purity;drug stability;high performance liquid chromatography;methodology;nonhuman;priority journal;trientine,"Hansen Jr, E. B.;Rushing, L. G.;Thompson Jr, H. C.",1985,,,0,0,
2871,Oral zinc therapy in Wilson's disease - an alternative to D-penicillamine. [German],"Recently Brewer et al. reported the possibility of an oral zinc therapy in Wilson's disease. We treated a 19 year old patient with decompensated liver cirrhosis due to Wilson's disease with zinc sulphate. D-penicillamine had to be withdrawn since proteinuria occurred under treatment. After the discontinuation of D-penicillamine an increase of serum copper almost up to the normal range was observed; concomitantly urinary copper elimination decreased. Under oral zinc sulphate therapy (145 mg/day) a drop in serum copper level was achieved and liver function improved; serum albumin, gamma globulins and prothrombin time reached normal values. The patient did not complain of any side effects during oral zinc sulphate therapy. Oral zinc therapy in Wilson's disease may be regarded as an alternative to D-penicillamine treatment when this drug has to be discontinued because of side effects.",adverse drug reaction;case report;congenital disorder;drug efficacy;drug indication;drug therapy;etiology;human;liver;liver cirrhosis;methodology;oral drug administration;priority journal;therapy;urine;Wilson disease;albumin;copper;furosemide;penicillamine;spironolactone;zinc;zinc sulfate,"Ramadori, G.;Keidl, E.;Hutteroth, Th",1985,,,0,0,
2872,Early diagnosis and treatment of hepatolenticular degeneration: clinical analysis of 92 cases. [Chinese],,adolescent;adult;article;child;differential diagnosis;female;human;male;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Chen, Z. R.",1985,Aug,,0,0,
2873,Advances in the study of hepatolenticular degeneration. [Chinese],,human;liver transplantation;metabolism;review;Wilson disease/di [Diagnosis];Wilson disease/th [Therapy];ceruloplasmin/an [Drug Analysis];copper/an [Drug Analysis];dimercaprol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];sulfate/dt [Drug Therapy];zinc/dt [Drug Therapy];zinc sulfate,"Liu, D. K.;Li, N. Z.;Chen, X. Z.;Yang, Y. F.",1985,Aug,,0,0,
2874,Synthesis of macrocyclic polyamines: Application to the increase of urinary excretion of copper in rats. [French],"The properties of six chelating agents that form highly stable complexes with transition metals has been examined in a comparative study for the elimination of copper in rats. For cyclic ligands, effectiveness grows with the stability constants of their complexes with this metal. With respect to Trien L<inf>5</inf> and Penicillamine L<inf>6</inf>, aliphalic ligands used in human therapy the 1,4,7,10,13-pentaazacyclopentadecane has proven to be more effective. After treatment by this macrocyclic polyamine, urinary excretion reached 60 times that observed in the control animals. The acute toxicity measurements in mice demonstrated that the intrinsically slightly toxic ligands are less so than their corresponding complexes. Considered in their entirety these results, with L<inf>2</inf>, permit the inference of an improvement in Wilson's disease therapy.","animal experiment;animal model;controlled study;copper excretion;dose response;dose time effect relation;drug analysis;drug blood level;drug comparison;drug efficacy;drug elimination;drug feces level;drug identification;drug interaction;drug monitoring;drug response;drug screening;drug stability;drug synthesis;drug tissue level;drug toxicity;drug urine level;infrared spectrometry;intoxication;intravenous drug administration;mouse;nonhuman;nuclear magnetic resonance;oral drug administration;priority journal;rat;therapy;urine;Wilson disease;1,4,7,10 tetraazacyclododecane;1,4,7,10 tetramethyl 1,4,7,10 tetraazacyclododecane;1,4,7,10,13 pentaazacyclopentadecane;1,5,8,12 tetraazacyclotetradecane;copper 64;copper chloride;metal chelate;new drug;penicillamine;radioisotope;trientine;unclassified drug","Pilichowski, J. F.;Borel, M.;Meyniel, G.",1984,,,0,0,
2875,Hypoparathyroidism in Wilson's disease,,editorial;endocrine system;etiology;human;hypoparathyroidism;liver;Wilson disease;penicillamine,"Piper, J. M.;Rosa, F. W.",1984,,,0,0,
2876,Current problems in Wilson's disease. [Spanish],,basal ganglion;cornea;human;kidney;liver;metabolism;pathology;prognosis;review;Wilson disease/di [Diagnosis];ceruloplasmin;copper;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Gilsanz Garcia, V.",1984,,,0,0,
2877,Luna fixata Ludemanni or the introduction of oral zinc therapy in official medicine,In the last decades a revival of interest in oral zinc therapy has been seen. In 1961 Schouwink described the use of oral zinc sulfate in the treatment of Wilson's disease. Later other applications of oral zinc therapy would follow. This article describes how in the 18th century Gaubius discovered that a panacea called 'Luna fixata' sold by a quack doctor named Ludeman consisted of zinc oxide and how in the 19th century extremely high dosages of zinc oxide were used to treat epilepsy.,central nervous system;drug efficacy;drug indication;epilepsy;history;human;review;therapy;Wilson disease;zinc;zinc oxide;zinc sulfate,"Hoogenraad, T. U.",1984,,,0,0,
2878,<sup>64</sup>Cu loading tests for monitoring zinc therapy in Wilson's disease,,central nervous system;clinical article;diagnosis;drug blood level;drug monitoring;drug therapy;human;liver;mineral balance;therapy;Wilson disease;copper 64;gluconate zinc;radioisotope;zinc;zinc acetate;zinc sulfate,"Van Den Hamer, C. J. A.;Hoogenraad, T. U.",1984,,,0,0,
2879,Computerised tomography in the longitudinal study of Wilson's disease. [German],"5 patients with proven Wilson's disease had clinical examinations and follow-up scans up to 6 years while under penicillamine treatment. Severe neurological deficits were associated with marked CT abnormalities. In all other cases clinical condition and CT finding were only loosely correlated. Under therapy, some hypodense areas normalized their attenuation partially or completely. In primarily normal CT's cupruresis did not induce alterations. As there is no firm correlation between CT findings and clinical involvement the CT examination is of limited value in prognosis.",case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;human;liver;Wilson disease;penicillamine,"Nix, W. A.;Ludwig, G.;Backmund, H.",1984,,,0,0,
2880,Contractures and hydrocephalus with penicillamine and maternal hypotension,"A female infant born to a mother treated with penicillamine for Wilson disease had congenital contractures, hydrocephalus, increased muscle tone, and an early death. No excess skin folds or herniae were observed. Following a hypotensive episode during surgery at 24 weeks' gestation, the mother was placed on 17-alpha-hydroxyprogesterone (Delalutin) until 32 weeks'. A normal male sibling was born previously after in-utero exposure to the same dose of penicillamine.",adverse drug reaction;cardiovascular system;case report;chemical teratogenesis;congenital disorder;contracture;drug therapy;embryo;fatality;fetus;human;hydrocephalus;hypertension;hypotension;joint contracture;maternal disease;muscle;muscle hypertonia;newborn;oral drug administration;pregnancy;prenatal drug exposure;therapy;Wilson disease;hydroxyprogesterone;hydroxyprogesterone caproate;penicillamine,"Gal, P.;Ravenel, S. D.",1984,,,0,0,
2881,Long-term treatment in chronic hepatitis. [German],"Before deciding on long-term treatment each case of chronic hepatitis requires histological classification and knowledge of the etiology. Drug and alcohol-induced chronic active hepatitis is treated by elimination of the causal agent alone. Additional measures are not necessary. Only symptomatic patients with chronic hepatobiliary disorders such as primary biliary cirrhosis and primary sclerosing cholangitis should be treated. The standard regimen consists of cholestyramine, fat-soluble vitamins and medium-chain triglycerides. Treatment with penicillamine has to be restricted to advanced stages. Whether liver transplantation plays a role in the treatment of PBC remains to be determined. Some types of chronic active hepatitis caused by metabolic or autoimmune disorders can be treated with a standardized therapy regimen. Hemochromatosis should be managed by regular phlebotomy. Wilson's disease requires lifetime penicillamine treatment and autoimmune hepatitis responds well to steroids or a combination of steroids and azathioprine. The optimal treatment for patients with Hb(s)Ag-positive and non-A, non-B chronic active hepatitis is still being investigated. Immunosuppression is not recommended. The benefit of long-term treatment with interferon and antiviral agents has yet to be studied.",chronic hepatitis;drug therapy;histology;human;liver;liver cirrhosis;review;therapy;azathioprine;interferon;penicillamine;prednisone,"Maier, K. P.",1984,,,0,0,
2882,Bio-inorganic effects of D-penicillamine in children and in the elderly,"The principle mechanisms of action of dimethylcysteine (D-penicillamine) are thiazolidine formation, sulphhydryl-disulphide exchange, chelation and superoxide dismutase-like activity; as a consequence, it can enter into many varied biological interactions. Thiazolidine formation with maturing collagen makes D-penicillamine potentially teratogenic; sulphhydryl-disulphide exchange allows the formation of a mixed disulphide with L-cysteine from the L-cystine dimer; chelation permits it to bind metals such as copper; and superoxide scavenging makes it theoretically capable of influencing the inflammatory response of specific cell systems. Not surprisingly, D-penicillamine is of value in the treatment of cystinuria, Wilson's disease, juvenile rheumatism, rheumatoid arthritis and various other conditions.",adult;aged;article;central nervous system;child;cystinuria;drug efficacy;drug toxicity;human;intoxication;joint;kidney;review;rheumatoid arthritis;therapy;Wilson disease;gold;penicillamine;thiazolidine;unclassified drug,"Kean, W. F.;Bellany, N.;Lock, C. J. L.;Adachi, J.",1984,,,0,0,
2883,Wilson's disease (hepatolenticular degeneration). [Spanish],,adolescent;adult;central nervous system disease/et [Etiology];child;eye disease/et [Etiology];hemolytic anemia/et [Etiology];human;kidney disease/et [Etiology];liver;multimodality cancer therapy;pathology;review;thrombocytopenia/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Dalmau Obrador, J.;Marti-Vilalta, J. L.;Aguilar Barbera, M.",1984,9 Jun,,0,0,
2884,Effective D-penicillamine treatment of an early diagnosed patient with Wilson's disease,,case report;central nervous system;child;drug therapy;heredity;human;liver;therapy;ceruloplasmin;copper 64;penicillamine;radioisotope,"Van Wouwe, J. P.;Van Weel-Sipman, M. H.;Giesberts, M. A. H.",1984,,,0,0,
2885,Effective treatment of Wilson's disease with oral zinc sulphate: Two case reports,"Most patients with Wilson's disease are treated with the potentially toxic cupriuretic agent penicillamine. The toxicity of zinc taken by mouth is low, and long term administration induces a negative copper balance. Two patients with severe neurological symptoms were given zinc sulphate by mouth three times daily in doses of 200 mg, later increased to 300 mg. One patient, a 21 year old man, started to receive zinc sulphate after his condition had deteriorated during treatment with cupriuretic drugs. The other, a 27 year old woman, was treated from the start with zinc sulphate. The conditions of both patients improved appreciably, and they were still receiving treatment with zinc sulphate roughly two years later. Effective depletion of body copper stores was shown by an intravenous radiocopper loading test and liver biopsy. No side effects were found. Wilson's disease may effectively be treated with zinc sulphate alone.",case report;central nervous system;copper blood level;drug therapy;human;liver;therapy;Wilson disease;penicillamine;zinc sulfate,"Hoogenraad, T. U.;Van Hattum, J.;Van Den Hamer, C. J. A.",1984,,,0,0,
2886,Optic neuropathy associated with penicillamine therapy in a patient with rheumatoid arthritis,Optic neuropathy developed in a patient with rheumatoid arthritis who had been receiving D-penicillamine for about 1 year. An associated finding included a 2+ positive antinuclear antibody test with a titer of 1:320. Optic disc swelling was resolved on high doses of intravenous steroids. The case resembles two previously reported cases of optic neuropathy which occurred in patients with Wilson's disease who were receiving penicillamine.,adverse drug reaction;article;case report;central nervous system;drug therapy;eye toxicity;human;intoxication;joint;nervous system;neurotoxicity;optic nerve disease;oral drug administration;peripheral nervous system;rheumatoid arthritis;therapy;toxicity;visual system;antinuclear antibody;dexamethasone;methylprednisolone;oxacillin;penicillamine;prednisone;pyridoxine;sulindac,"Klingele, T. C.;Burde, R. M.",1984,,,0,0,
2887,Fulminant hepatic and renal failure complicating Wilson's disease,We report a case of fatal fulminant liver failure complicating Wilson's disease that is unique in several respects. The illness supervened after several years of medical noncompliance in a patient who had been previously diagnosed and successfully treated with penicillamine. Re-institution of penicillamine therapy 2 weeks prior to the fulminant decompensation failed to prevent it. Renal failure in this patient was apparently secondary to rhabdomyolysis. Addition of penicillamine to a peritoneal dialysis solution allowed chelatin and removal of over 14 mg per day of copper but without apparent benefit. Exchange transfusion and high dose dexamethasone therapy (24 mg/day) were equally ineffective in reversing the liver failure. Other reported cases have also been fatal. The best treatment for fulminant Wilson's disease is prevention by diagnosis in a pre-symptomatic stage and institution of carefully supervised life-long therapy with penicillamine.,case report;diagnosis;human;kidney;kidney failure;liver;liver failure;muscle;rhabdomyolysis;therapy;Wilson disease;penicillamine,"Rector Jr, W. G.;Uchida, T.;Kanel, G. C.",1984,,,0,0,
2888,Syndrome of gonadotrophin-resistant ovaries and Wilson' disease: One case. [French],,amenorrhea;case report;central nervous system;diagnosis;drug resistance;drug therapy;endocrine system;female genital system;histology;human;intramuscular drug administration;liver;oral drug administration;ovary;therapy;Wilson disease;gonadorelin;gonadotropin;penicillamine,"Hartemann, P.;Leclere, J.;Thomas, J. L.",1983,,,0,0,
2889,Diagnostic value and meaning of radiocopper-loading test abnormalities in Wilson's disease. [French],"Wilson's disease in this patient was suspected from the association of histological features of chronic active hepatitis and increased hepatic-copper concentration. However, the patient exhibited long-standing cholestasis, demonstrated neither the Kayser-Fleischer ring nor neurological symptoms, and had a serum-ceruloplasmin concentration within the normal range. The time course of the plasma-<sup>64</sup>Cu levels in this patient was compared with those found in four other subjects: A normal subject, two patients with typical Wilson's disease and a patient with primary biliary cirrhosis. Similar time courses were observed for both the patient with suspected Wilson's disease and the two typical cases, thus unequivocally establishing the diagnosis. This pattern differed from that of the normal subject by the absence of a secondary rise in plasma-<sup>64</sup>Cu concentration. In the patient with primary biliary cirrhosis, the time course was intermediate between that of the normal subject and that of patients with Wilson's disease. These results suggest that: 1) a radiocopper-loading test is useful in the diagnosis of difficult cases of Wilson's disease, especially when the ceruloplasmin level is normal; 2) the absence of a secondary increase in plasma <sup>64</sup>Cu levels in Wilson's disease is, to a large extent, independent of the decrease in serum-ceruloplasmin; it seems to be more related to dilution of the isotope in an expanded hepatic copper pool and to abnormalities of intrahepatic copper distribution.",blood and hemopoietic system;diagnosis;drug administration;histology;human;human cell;liver;normal human;therapy;Wilson disease;ceruloplasmin;copper 64;penicillamine;radioisotope,"Mavier, P.;Meignan, M.;Wirquin, E.",1982,,,0,0,
2890,Two cases of verruciform elastosis after a long treatment with D-penicillamine for Wilson's disease. [French],,adverse drug reaction;case report;drug therapy;elastosis perforans serpiginosa;histology;human;intoxication;oral drug administration;skin;skin elastosis;skin toxicity;therapy;verruca vulgaris;Wilson disease;penicillamine;promethazine,"Sfar, Z.;Lakhoua, M.;Kamoun, M. R.",1982,,,0,0,
2891,D-penicillamine induced membranous nephropathy. [Spanish],,adverse drug reaction;case report;drug therapy;human;intoxication;joint;kidney;membranous glomerulonephritis;nephrotic syndrome;nephrotoxicity;oral drug administration;proteinuria;rheumatoid arthritis;therapy;Wilson disease;penicillamine,"Prieto Carles, C.;Gutierrez Millet, V.;Barrientos, A.",1982,,,0,0,
2892,Haemolytic anaemia associated with severe hepatic dysfunction as the first manifestation of Wilson's disease. [Dutch],,blood and hemopoietic system;case report;drug therapy;hemolytic anemia;human;kayser fleischer ring;liver;liver failure;liver function;therapy;visual system;Wilson disease;ceruloplasmin;penicillamine,"Vasen, H. F. A.;Sindram, J. W.;Struyvenberg, A.",1982,,,0,0,
2893,Results of long-term therapy of Wilson's disease. [Czech],"The authors report their results with the treatment of 52 subjects with Wilson's disease; 30 of these patients were followed up for 5-20 years. The patients were treated with penicillamine, pyridoxine and a low copper-diet. Undesirable effects of penicillamine were observed in 12 patients, in 3 it was necessary to discontinue treatment and to replace it by triethylenetetramine dihydrochloride. Five patients died within one year of treatment, others after 3, 7 and 9 years. The neurological finding of patients treated for prolonged periods improved completely in 9 cases, improved considerably in 9 and improved in 3. The total ratio of improved patients is 81,3%. The prognosis of Wilson's disease is much better since penicillamine therapy was started. The hepatocerebral form and the disease in young people under 15 years is a serious problem. Triene is a suitable drug for those patients where penicillamine produces marked, undesirable side-effects.",central nervous system;liver;low copper diet;major clinical study;therapy;Wilson disease;copper;penicillamine;pyridoxine,"Hartl, J.;Hauftova, D.",1982,,,0,0,
2894,Biochemical and clinical changes in heterozygotes with Wilson's disease. [Czech],"The investigation is focused on heterozygous children of patients with Wilson's disease. A detailed biochemical, clinical and electroencephalographic examination was made. In almost all children a reduced copper and cerulloplasmin serum level was found and high urinary copper excretion during the loading test with penicillamine. The finding is different from results in adult heterozygotes. In 30% of the children a pathological neurological finding was revealed and in 75% EEG abnormalities. The authors discuss causes of these changes which were not observed so far by others authors.",central nervous system;copper urine level;electroencephalography;heredity;liver;major clinical study;Wilson disease;ceruloplasmin;penicillamine,"Marecek, Z.;Nevsimalova, S.",1982,,,0,0,
2895,Studies on determining the mutagenicity risk of triethylenetetramine. [German],"Triethylenetetramine (TETA) is the only available effective drug for the treatment of patients with Wilson's disease and with simultaneous intolerance to D-penicillamine. In the Ames test, however, both TETA and the structurally similar tetramine BE 6184 are mutagenic. The naturally occurring spermine, a closely related tetramine differing only in one additional methylene group in every carbon chain, shows no mutagenicity. TETA does not exhibit any mutagenic potency in the micronucleus test.",adverse drug reaction;Ames test;animal experiment;drug comparison;heredity;in vitro study;liver;micronucleus test;mutagenicity;Wilson disease;cyclophosphamide;mitomycin C;penicillamine;spermine;tetramethylammonium hydroxide derivative;trientine;unclassified drug,"Heinz, N.;Schroeder, H. F.",1981,,,0,0,
2896,The syndrome of primary biliary cirrhosis,"Primary biliary cirrhosis, a chronic systemic disease, likely involves a disturbance in the immune process. The significant alterations in copper metabolism in this disorder are, we believe, related to progressive intrahepatic cholestasis and impairment in normal hepatobiliary copper clearance. A trial of D-penicillamine treatment suggests that this drug may benefit some patients. However, enthusiasm for the drug's use must be tempered by the fact that it may adversely affect 20% of patients; also, data regarding therapeutic effectiveness are not definitive. Therefore, we recommend using D-penicillamine for primary biliary cirrhosis only in control trials.",abstract report;bile duct;biliary cirrhosis;cholestasis;congenital disorder;drug therapy;heredity;liver;primary biliary cirrhosis;short survey;therapy;Wilson disease;copper;penicillamine;placebo,"Dickson, E. R.",1981,,,0,0,
2897,Wilson's disease,,chelation;congenital disorder;drug therapy;etiology;heredity;liver;pathogenesis;short survey;therapy;Wilson disease;ceruloplasmin;copper;dimercaprol;penicillamine,"Scheinberg, I. H.",1981,,,0,0,
2898,Use of penicillamine in Wilson-Konovalov's disease. [Russian],,ceruloplasmin blood level;copper urine level;drug blood level;drug therapy;drug urine level;major clinical study;preliminary communication;therapy;Wilson disease;wilson konovalov disease;penicillamine,"Vakharlovsky, V. G.;Nikitina, L. I.;Bondarchuk, A. N.",1980,,,0,0,
2899,Immunohistological findings in renal biopsies in Wilson's disease. [German],"12 patients with Wilson's disease were examined by means of renal biopsy. In 9 of these patients a slight (4 patients) or a strong proteinuria (5 patients) appeared during the therapy with D-penicillamine. A biopsy was performed in 3 patients before the beginning of the therapy with D-penicillamine. The patients with severe proteinuria showed the largest immunohistological changes (partly distinct immune complex nephritis with epimembranous IgG- and complement-(C<inf>3</inf>) depositions - electron optically membranous glomerulonephritis). In rebiopsy after a stoppage of the medicament of 1 year, only a slight tendency to improvement was to be recognized.",case report;diagnosis;electron microscopy;histology;immune complex disease;immunohistology;kidney;kidney biopsy;prolactin blood level;proteinuria;Wilson disease;penicillamine,"Storch, W.;Ditscherlein, G.;Lange, E.;Lossner, J.",1980,,,0,0,
2900,Transient external ophthalmolplegia in Wilson's disease,"An 18-year-old female with classical Wilson's disease had a mild disturbance of ocular motility while on adequate doses of penicillamine. During an abrupt deterioration of her condition due to discontinuation of therapy, marked external ophthalmoplegia was observed. A dramatic improvement of ocular motility occurred 4 days after reinstitution of high doses of penicillamine. The transitory nature of the ophthalmoplegia and the dramatic therapeutic effect of penicillamine suggests that ocular motility abnormalities in Wilson's disease serves as a delicate indicator for copper accumulation in the basal ganglia.",case report;drug therapy;external ophthalmoplegia;eye movement;muscle;ophthalmoplegia;peripheral nervous system;therapy;visual system;Wilson disease;copper;penicillamine,"Gadoth, N.;Liel, Y.",1980,,,0,0,
2901,Regression of a Kayser-Fleischer ring in a case of Wilson's disease on penicillamine therapy. [German],"The disappearance of a Kayser-Fleischer ring induced by the administration of penicillamine (D-penicillamine) for 17 years is described. The ring disappeared only in the lateral and medial portions, leaving superior and inferior crescents. Possible mechanisms of this partial regression of the ring are discussed.",adverse drug reaction;case report;cornea;drug therapy;kayser fleischer ring;oral drug administration;therapy;visual system;Wilson disease;penicillamine,"Hiti, H.;Harpf, H.;Wutz, W.;Schmut, O.",1980,,,0,0,
2902,Liquid nitrogen cryotherapy in a case of elastosis perforans serpiginosa,This is a case report documenting successful treatment of elastosis perforans serpiginosa with liquid nitrogen in a patient who took penicillamine for Wilson's disease.,case report;cryotherapy;elastosis perforans serpiginosa;human;therapy;Wilson disease;penicillamine,"Rosenblum, G. A.",1983,,,0,0,
2903,Hudson Memorial Lecture: Wilson's disease: Genetics and biochemistry - their relevance to therapy,"Wilson's disease is an inherited metabolic disorder affecting children, adolescents and young adults. Before puberty the initial signs and symptoms are almost always related to liver damage, with or without haemolysis. After puberty neurological signs become increasingly prominent, always involving the motor centres, sometimes personality, never the sensory nervous system. The most characteristic physical sign is the Kayser Fleischer corneal pigment ring resulting from deposition of copper in Descemet's membrane. The primary genetic defect is not known but the disease appears to result from a failure, by the hepatocytes, to excrete copper via the bile. As a result this metal accumulates first in the liver then, when this organ is saturated, in the brain, the corneae, and to a lesser extent the kidneys. Once present in excess in the tissues copper poisons various enzyme systems leading to cellular damage and death. At present there is no satisfactory explanation for the pleomorphic nature of the disease much less of the often gross assymetry of the lesions in the brain. Treatment entails the establishment of a negative copper balance until the abnormal body stores of the metal have been removed. Thereafter the patient must be kept in balance for life. There are two main drugs available for this purpose, penicillamine and triethylene tetramine (Trientine). Both will achieve biochemical and clinical reversal of the disease. Pencillamine can give rise to a wide range of toxic reactions, mostly on an immunological basis; it is therefore essential to monitor the blood count and renal function regularly. Less is known at present of the potential of Trientine to induce unwanted side effects. Wilson's disease is characterized by recessive inheritance. It can be diagnosed in the presymptomatic stage by finding abnormalities of copper metabolism. All families should be screened and, where appropriate, prophylactic treatment started, thus aborting the clinical evolution of the disease.",clinical feature;drug comparison;drug therapy;human;inheritance;short survey;therapy;Wilson disease;copper;penicillamine;trientine,"Walshe, J. M.",1983,,,0,0,
2904,Metallothionein - aspects related to copper and zinc metabolism,"Metallothionein is a cysteine-rich, low molecular weight protein that binds zinc, copper and cadmium. It is inducible in liver, kidney and intestine by glucocorticoids, changes in the dietary zinc supply, acute administration of various metals, food restriction, infection, stress and endotoxin treatment. Regulation of synthesis involves altered gene expression. The protein is fairly rapidly degraded when zinc is the primary metal species bound, but the degradation rate is diminished when cadmium or copper are bound as well. The net result of metallothionein production seems to be accumulation of bound metal and/or intracellular metal redistribution. The accumulation of copper in various tissues of individuals with Menkes' and Wilson's disease may be related to altered metallothionein turnover. The physiological function is not clear, but the response of metallothionein to hormonal stimuli is suggestive of an important role in cellular metabolism.",etiology;gene expression;heredity;human;Menkes syndrome;review;Wilson disease;copper;metallothionein;zinc,"Cousins, R. J.",1983,,,0,0,
2905,3 Years of continuous oral zinc therapy in 4 patients with Wilson's disease,"A competitive relationship exists between copper and zinc: among other effects, excessive dietary zinc is known to decrease the absorption of copper from the gastro-intestinal tract. The purpose of this study is to investigate the effectiveness of oral zinc therapy in 4 patients with Wilson's disease, who, during a 3-year period, took zinc as their only medication to influence their copper metabolism. Physical examinations, oral <sup>64</sup>Cu loading tests, plasma concentrations of copper, zinc and ceruloplasmin, and the urinary copper excretion were used to monitor the effect of therapy. The dosages used ranged from 3 x 100 to 3 x 400 mg zinc sulphate per day. The clinical and biochemical results of the oral zinc therapy were good in all 4 patients and no toxic side-effects were seen. Our conclusion from this study is that oral zinc may well be a low toxic alternative to D-penicillamine in the treatment of Wilson's disease.",absorption;central nervous system;clinical article;digestive system;drug therapy;excretion;gastrointestinal tract;human;liver;plasma;therapy;Wilson disease;ceruloplasmin;copper;copper 64;penicillamine;radioisotope;zinc;zinc sulfate,"Hoogenraad, T. U.;Van den Hamer, C. J. A.",1983,,,0,0,
2906,Trientine,,copper blood level;copper urine level;drug analysis;drug comparison;drug efficacy;drug identification;drug screening;drug synthesis;drug toxicity;human;human experiment;intoxication;liver;metabolic disorder;pharmacokinetics;pregnancy;short survey;therapy;Wilson disease;chelating agent;copper;new drug;penicillamine;trientine,"Hopkins, S. J.",1983,,,0,0,
2907,True hepatic Wilson's disease. [Italian],"Fourteen cases of Wilson's disease, 9 of which in pure hepatic form are presented. Earliest clinical sign of liver disease was hepatosplenomegaly with altered indexes of hepatic function. The disease was found in 4 couples of brothers and sisters of families reported. For all cases diagnosis was based on the values of ceruloplasmin, serum copper, basal urine copper and urine copper after D-penicillamine. Furthermore in 8 cases very increased copper concentration in the liver was demonstrated. D-penicillamine therapy produced hepatic improvement in 8 cases, 6 of which affected by only hepatic form and the treatment was fairly tolerated. In 1 case this therapy caused nephrotic syndrome it was replaced with Trien-2HCL. Wilson's disease in its pure hepatic form must be considered in the differential diagnosis of liver diseases in pediatric age, especially when markers of viral hepatitis are absent. The identification of pure hepatic form provides early diagnosis of Wilson's disease, basic requirement for an effective therapy.",adolescent;article;blood;child;female;human;male;preschool child;urine;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/an [Drug Analysis];copper;penicillamine/dt [Drug Therapy],"Ciravegna, B.;Giacchino, R.;Marazzi, M. G.",1983,1983,,0,0,
2908,The orphan drug products - another solution?,,editorial;esophagus;esophagus varices;prescription;therapy;Wilson disease;monoethanolamine oleate;penicillamine;trientine,"Archambault, G. F.",1983,,,0,0,
2909,Sequential laparoscopic observation of the liver in a case of Wilson's disease treated with D-penicillamine. [Japanese],,case report;diagnosis;drug therapy;histology;human;laparoscopy;liver;therapy;Wilson disease;penicillamine;prednisone,"Kado, Y.;Okita, K.;Ando, K.",1983,,,0,0,
2910,Wilson's disease. [French],,autosomal recessive inheritance;central nervous system;child;diagnosis;drug therapy;heredity;histology;human;kayser fleischer ring;liver;liver disease;therapy;visual system;Wilson disease;dimercaprol;penicillamine;pyridoxine,"Albert, J.;Favre, R.",1983,,,0,0,
2911,A case of asymptomatic Wilson's disease. [Japanese],,case report;drug therapy;human;therapy;Wilson disease;penicillamine,"Hayashi, H.;Hukui, K.;Murakami, H.",1983,,,0,0,
2912,Penicillamine-induced myasthenia in rheumatoid arthritis: Its clinical and genetic features,"The clinical features and genetic background of 18 patients with rheumatoid arthritis were investigated following the development of penicillamine-induced myasthenia (PIM). The initial myasthenic symptoms in all patients consisted of variable diplopia and/or ptosis with progression to a more generalised involvement in 7 of them. No clinical, humoral, or genetic factor was determined which would allow identification of individuals developing generalised as opposed to ocular myasthenia. Withdrawal of penicillamine was associated over 4-60 weeks with a slow resolution of symptoms, facilitated in 12 patients by the use of anticholinesterase agents. In 2 patients a persistent partial unilateral ptosis remained after 15 and 25 months, while in a further patient diplopia was present 42 months after resolution of the other myasthenic symptoms. The patients with PIM when compared with a healthy 'control' population had a significant increase in HLD Dr1 (p corr<0.005) and an absence of HLA Dr3. A genetic susceptibility to the development of PIM, distinct from that observed in myasthenia gravis of spontaneous onset, is suggested by this abnormal distribution of HLA Dr antigens.",adverse drug reaction;clinical article;clinical study;diplopia;drug therapy;genetics;heredity;human;joint;muscle;myasthenia;myasthenia gravis;oral drug administration;ptosis;rheumatoid arthritis;therapy;visual system;cholinesterase inhibitor;HLA antigen;penicillamine,"Delamere, J. P.;Jobson, S.;Mackintosh, L. P.;Wells, L.;Walton, K. W.",1983,,,0,0,
2913,Cutis laxa and low serum zinc after antenatal exposure to penicillamine,,clinical article;cutis laxa;cystinuria;fetus;human;infant;inguinal hernia;joint;mother;pregnancy;rheumatoid arthritis;small intestine;Wilson disease;zinc blood level;ceruloplasmin;collagen;copper;penicillamine;pyridoxine;zinc,"Harpey, J. P.;Jaudon, M. C.;Clavel, J. P.;Galli, A.;Darbois, Y.",1983,,,0,0,
2914,Hypoparathyroidism in Wilson's disease,"An 11-year-old girl with Wilson's disease presented with mild hypocalcemia (8.0 mg per deciliter), hypophosphatemia (2.7 mg per deciliter), hypercalciuria (569 mg per day), and hyperphosphaturia (tubular reabsorption of phosphate, 67 per cent). The hyperphosphaturia and hypercalciuria were attributed to the Fanconi syndrome, a known component of Wilson's disease. Circulating immunoreactive parathyroid hormone was usually undetectable or, occasionally, detectable at minimal levels in the presence of depressed blood levels of ionized calcium. Normal levels of ionized calcium were not maintained throughout a 24-hour monitoring period. The patient had tetany during a period of rapid reduction in ionized calcium levels, and an appropriate rise in circulating immunoreactive parathyroid levels was never demonstrated. Induced hypocalcemia during citrate infusion did not stimulate parathyroid secretion, nor did infusion of magnesium. We conclude that parathyroid insufficiency may be associated with Wilson's disease. We speculate that it is due to deposition of copper in the parathyroid glands.",case report;central nervous system;drug therapy;endocrine system;Fanconi anemia;human;hypercalciuria;hyperphosphaturia;hypocalcemia;hypoparathyroidism;hypophosphatemia;kidney;oral drug administration;school child;tetany;therapy;Wilson disease;calcitriol;ergocalciferol;gluconate calcium;magnesium sulfate;menadione;penicillamine;pyridoxine;spironolactone,"Carpenter, T. O.;Carnes Jr, D. L.;Anast, C. S.",1983,,,0,0,
2915,Wilson's disease. [Spanish],,article;case report;child;female;human;urine;Wilson disease/di [Diagnosis];ceruloplasmin/an [Drug Analysis];copper;diagnostic agent;penicillamine,"Prudencio, R.;Betancourt, F.;Larrain, F.;Danus, O.",1983,1983,,0,0,
2916,Long-term management of inherited renal tubular disorders,"In inherited renal tubular disorders with isolated defects of tubular transport medical treatment is usually either not indicated or is simple and effective. In some inherited metabolic disorders with complex defects of renal tubular transport a specific therapy is known. For example, in galactosemia and hereditary fructose intolerance crude products may be restricted or in cases of Wilson's disease copper stores may be reduced. In idiopathic Fanconi syndrome, cystinosis, oculocerebrorenal syndrome and glycogenosis Fanconi-Bickel, a symptomatic replacement treatment based on supplementation of water, electrolytes and vitamin D has improved the non-uremic survival of these patients considerably within the last 20 years. For long-term management of inherited renal tubular disorders, treatment of tubular dysfunction, chronic renal failure, and involved extrarenal organs must be supported by genetic counseling and assistance for social integration.",clinical study;etiology;Fanconi anemia;genetic disorder;heredity;inheritance;kidney;kidney tubule;kidney tubule disorder;metabolic disorder;pathogenesis;review;survey;therapy;alpha galactosidase;ascorbic acid;bicarbonate;calcitriol;dithiothreitol;electrolyte;etacrynic acid;hydrochlorothiazide;magnesium;mercaptamine;penicillamine;phosphatidylcholine sterol acyltransferase;potassium;pyridoxine;tiopronin;triamterene;water,"Manz, F.;Schaerer, K.",1982,,http://dx.doi.org/10.1007/BF01715841,0,0,
2917,A new look at cirrhosis,"There have been modest advances in our understanding of the pathogenesis of certain types of cirrhosis, but the present system om classification is not entirely satisfactory. How, for instance, do we classify the type of cirrhosis found in an individual who drinks 80 g of alcohol a day, is hepatitis BsAg-positive and is noted to be an MZ heterozygote for alpha-1-antitrypsin deficiency? Many cases of cirrhosis may have multifactorial origins; alcohol and the hepatitis B virus may act synergistically in this respect. Some types of cirrhosis, for instance that due to hepatitis B virus, are now potentially preventable, while others may be partially reversible. In inherited disorders such as Wilson's disease and haemachromatosis, for which specific treatment exist, it is vital to screen other family members. In established cirrhosis associated with disorders such as non-A, non-B hepatitis, primary biliary cirrhosis and Indian childhood cirrhosis, the antifibrogenic drugs penicillamine and colchicine hold promise, although it is questionable whether either drug should, as yet, be used outside the confines of a controlled trial. Finally, in some forms of end-stage cirrhosis, liver transplantation should be considered.",alcohol liver cirrhosis;alcohol liver disease;biliary cirrhosis;chronic active hepatitis;classification;enzyme deficiency;hemochromatosis;Indian childhood cirrhosis;liver;liver cirrhosis;primary biliary cirrhosis;therapy;virus hepatitis;Wilson disease;alcohol;alpha 1 antitrypsin;azathioprine;calcitriol;colestyramine;corticosteroid;guestran;menadione;penicillamine;propranolol;retinol;unclassified drug,"Warnes, T. W.",1982,,,0,0,
2918,Patterns of hepatocyte injury in man,"Three patterns of hepatocyte injury in man, direct, immunological, and cholestatic, are described. The characteristics of the direct pattern are predominantly mitochondrial damage, central (zone 3) necrosis, and, usually, fatty change. It can be subdivided into the alcohol type (also seen with obesity, in diabetes, as a reaction to perhexiline, in Wilson's disease, and in Indian childhood cirrhosis) and the Reye's syndrome type (also seen with tetracycline toxicity, fatty liver of pregnancy, and cytotoxic drugs). Reactive drug metabolites, metal poisoning, and anoxia are also associated with the direct pattern of hepatocyte injury. The immunological pattern is characterized by damage to cell membranes with piecemeal necrosis of periportal (zone 1) hepatocytes and mononuclear-cell infiltration. Examples include chronic active hepatitis, primary biliary cirrhosis, and drug reactions such as those to halothane. In the cholestatic pattern there is disturbance of the bile-secretory mechanism with retention of bile within the hepatocytes. Cholestatic liver injury may be intrahepatic, as in sex-hormone cholestasis, or extrahepatic, as in choledocholithiasis or carcinoma of the bile ducts. Identification of the type of hepatocyte injury is valuable in diagnosis, in assessing prognosis, and in selecting treatment.",adverse drug reaction;bile duct;cholestasis;cholestatic hepatitis;endocrine system;etiology;fatty liver;hepatitis;histology;immunology;intoxication;liver;liver cell damage;liver necrosis;liver toxicity;rye syndrome;Wilson disease;acetylcysteine;alcohol;alkylating agent;chlorpromazine;colestyramine;corticosteroid derivative;halothane;heavy metal;isoniazid;levamisole;metal;methionine;paracetamol;penicillamine;perhexiline;perhexiline maleate;phenobarbital;propylthiouracil;prostaglandin derivative;rifampicin;sex hormone;tetracycline,"Sherlock, S.",1982,,,0,0,
2919,A prospective trial of D-penicillamine in primary biliary cirrhosis,"There is no effective treatment for primary biliary cirrhosis, a progressive and usually fatal liver disease in which hepatic copper concentrations are often as high as those in Wilson's disease. We evaluated D-penicillamine in the treatment of primary biliary cirrhosis. In a prospective double-blind trial, 26 patients received D-penicillamine (250 mg four times a day), and 26 received an identical placebo. Although the desired urinary excretion of copper was achieved in patients taking D-penicillamine, there was no improvement in survival or symptoms after 28 months. Serum bilirubin and alkaline phosphatase increased equally in both groups. Alanine and aspartate aminotransferases were lower in the D-penicillamine group, but serum albumin was also lower in this group. Liver histology worsened equally in both groups. Major side effects, some appearing more than 24 months after the start of treatment, occurred in 31 per cent of the patients receiving D-penicillamine. Less serious side effects occurred in an additional 46 per cent. We conclude that D-penicillamine at the dosage we used is not effective in the treatment of primary biliary cirrhosis and is associated with a high incidence of serious side effects.",adverse drug reaction;arthralgia;controlled study;histology;kidney;liver;major clinical study;mouth;mouth ulcer;muscle;myasthenia;nephrotoxicity;oral drug administration;primary biliary cirrhosis;proteinuria;rash;stomatitis;taste;therapy;penicillamine,"Matloff, D. S.;Alpert, E.;Resnick, R. H.;Kaplan, M. M.",1982,,,0,0,
2920,Penicillamine. [French],,cystinuria;drug induced disease;drug structure;drug tolerance;joint;pharmacokinetics;prescription;rheumatoid arthritis;short survey;therapy;Wilson disease;penicillamine,"Wiederkehr, P.;Raul, P.;Netter, P.",1982,,,0,0,
2921,Skin changes during penicillamine treatment in a patient with Wilson's disease. [German],,adverse drug reaction;case report;histology;intoxication;oral drug administration;skin toxicity;therapy;Wilson disease;penicillamine,"Erlach, E.",1982,,,0,0,
2922,Peritoneal dialysis for eliminating copper in patients with Wilson's disease. [French],"We report a case of Wilson's disease, with a rapidly progressive course, in which peritoneal dialysis was performed. The physiopathology of acute features occurring during the course of the disease is reviewed. The different methods for eliminating copper, particularly peritoneal dialysis, are discussed. The authors recall the precautions which are necessary when initiating D-penicillamin therapy.",case report;liver;liver cirrhosis;methodology;peritoneal dialysis;peritoneum;therapy;Wilson disease;copper,"Guerin, J. M.;Raux, M.;Meresse, S.;Lamotte, M.",1982,,,0,0,
2923,Wilson's disease: report of two cases. [Chinese],"Wilson's disease is a rare inborn error of metabolism inherited as an autosomal recessive trait. The exact etiology of this disease is still unknown. It is characterized by degenerative changes of the central nervous system, cirrhosis of the liver and renal dysfunction. The pathognomonic finding is the presence of greenish-brown Kayser-Fleischer rings in the limbus of the cornea. Early treatment with D-penicillamine will improve the outcome. The first patient was a 12-year-old boy who had dysarthria, tremor clumsiness and numbness of the right upper extremity. He survived and gradually improved after administration of D-penicillamine and a low copper diet. Another patient was a 14-year-old girl who had the clinical manifestation of ascites, jaundice and abdominal distension Her consciousness rapidly deteriorated several days after admission and she finally died of hepatic failure. Both patients had Kayser-Fleischer rings in their corneas. They had a low serum level of ceruloplasmin and increased urinary excretion of copper.",case report;diagnosis;drug therapy;kayser fleischer ring;liver;therapy;visual system;Wilson disease;ceruloplasmin;copper;penicillamine,"Kuo-Cheng, Chang;Yau-Shing, Lee;Fu-Yang, Huang;Hsi-Hsiang, Huang",1982,,,0,0,
2924,Penicillamine induced elastosis perforans serpiginosa: An ultrastructural study of two cases,"An electron microscopic study of two cases of penicillamine-induced EPS has revealed in addition to the 'lumpy-bumpy' aspect of the elastic fiber, morphologic changes in collagen fibers.",adverse drug reaction;case report;elastic fiber;elastosis perforans serpiginosa;electron microscopy;oral drug administration;therapy;Wilson disease;collagen;collagen fiber;penicillamine,"Reymond, J. L.;Stoebner, P.;Zambelli, P.",1982,,http://dx.doi.org/10.1111/j.1600-0560.1982.tb01072.x,0,0,
2925,Electrophysiological findings in Wilson's disease after long-term medication with D-penicillamine. [German],,adverse drug reaction;blood and hemopoietic system;central nervous system;diagnosis;electromyography;human cell;major clinical study;muscle;myasthenia;oral drug administration;peripheral nervous system;therapy;Wilson disease;penicillamine;pyridoxine,"Krause, T.;Wagner, A.;Lossner, J.",1982,,,0,0,
2926,Wilson's disease. [German],,central nervous system;editorial;human;liver;therapy;Wilson disease;penicillamine,"Lange, J.;Strohmeyer, G.",1982,,,0,0,
2927,Role of catecholamines in the biochemical mechanisms of the pathogenesis of hepatocerebral dystrophy. [Russian],"In 48 patients with hepatocerebral dystrophy the principal parameters of the catecholamine metabolism were examined. Pronounced changes characterized primarily by a considerable diminution of dopamine and noradrenaline excretion and an increase of the excretion of their immediate precursor, i.e. DOPA, were noted. On the basis of the data obtained it was assumed that the synthesis of these neurotransmitting catecholamines was depressed. In the course of treatment with d-penicillamine which is capable of mobilizing copper and stimulating its excretion from the body a statistically significant increase of the dopamine excretion (as compared with its initial level) was noted, and in patients with the graver rigid-arrhythmohyperkinetic form of the disease the excretion of not only dopamine, but also noradrenaline, was increased. It is supposed that the disturbances of catecholamine metabolism in hepatocerebral dystrophy have a complicated mechanism, and are associated with both the grave hepatic pathology and disturbances of copper metabolism. In this connection additional methods of treating that disease are offered. These methods influence catecholamine metabolism, and act primarily on extrapyramid motor, and also psychic disorders. The studies carried out by the author make a contribution to the existing concepts of the biochemical mechanisms of the hepatocerebral dystrophy pathogenesis, and expand the possibilities of treating the grave hereditary disease.",adolescent;adult;article;human;metabolism;urine;Wilson disease;adrenalin;catecholamine;copper;dopamine;dopamine beta monooxygenase;homovanillic acid;noradrenalin;thiophene derivative;tiodonium chloride;vanilmandelic acid,"Barkhatova, V. P.",1982,,,0,0,
2928,penicillamine: penicillamine pharmacology and clinical applications. [Italian],,connective tissue disease;diagnosis;digestive system;drug therapy;gastrointestinal toxicity;heavy metal poisoning;human;intoxication;joint;liver;liver disease;liver toxicity;skin toxicity;soft tissue;therapy;Wilson disease;heavy metal;penicillamine,"Gattoni, A.;de Donato, M. T.;Catalano, G.;Astarita, C.;Bernabo, R.;Altucci, P.",1982,,,0,0,
2929,Persistent transaminasemia and fatty liver. Their use in the diagnosis of presymptomatic Wilson's disease,"A 4 1/2 -year-old asymptomatic girl with persistent elevated serum transaminase levels for eight months was found to have Wilson's disease. The diagnosis was suspected by the presence of fatty liver and nonspecific chronic hepatitis on liver biopsy and was proved by studies of copper metabolism, including determinations of serum ceruloplasmin and hepatic copper concentrations. Unexplained persistent transaminase elevations in children demand investigation by needle liver biopsy. The presence of fatty liver and hepatitis should raise the possibility of Wilson's disease, which may then be confirmed by more specific tests. Advantages to early diagnosis include the institution of specific therapy and prevention of progressive liver disease.",aspartate aminotransferase blood level;autosomal recessive inheritance;case report;diagnosis;fatty liver;hepatitis;liver;preschool child;Wilson disease;aminotransferase;copper;penicillamine;pyridoxine,"Stillman, A. E.;Rohr, L. R.",1982,,,0,0,
2930,D-Penicillamine-induced pemphigus syndrome,"D-Penicillamine is a chelating agent which is effective in the treatment of Wilson's disease, cystinuria, and lead poisoning. In recent years, it has also been used to treat patients with rheumatoid arthritis with good results. The adverse effects of D-penicillamine are many. These include loss of taste, nephrotic syndrome, lupus erythematosus-like syndrome, polymyositis, dermatomyositis, myasthenia gravis, and agranulocytosis. Beginning in 1969, D-penicillamine was reported to induce a pemphigus eruption. We present a patient with D-penicillamine-induced pemphigus erythematosus and review previously reported cases.",adverse drug reaction;case report;erythematous pemphigus;oral drug administration;pemphigus vulgaris;rheumatoid arthritis;therapy;azathioprine;captopril;chlorpropamide;cyclophosphamide;digitalis;penicillamine;penicillin G;phenylbutazone;prednisolone;prednisone;rifampicin,"Yung, C. W.;Hambrick Jr, G. W.",1982,,,0,0,
2931,Copper in pediatrics. [French],,central nervous system;child;clinical feature;diagnosis;drug absorption;drug blood level;drug distribution;drug elimination;drug metabolism;drug toxicity;heredity;human;intoxication;liver;Menkes syndrome;newborn;pharmacokinetics;review;survey;therapy;Wilson disease;ceruloplasmin;copper;cytochrome c oxidase;enzyme;monophenol monooxygenase;penicillamine;protein;pyridoxine;superoxide dismutase;trientine,"Vallee, L.",1982,,,0,0,
2932,Establishment of a new therapy for Wilson's disease: Negative copper balance of Wilson's disease patients on oral zinc therapy,,abstract report;central nervous system;clinical article;drug therapy;human;liver;therapy;Wilson disease;copper;penicillamine;zinc acetate,"Hill, G. M.;Brewer, G. J.;Prasad, A. S.;Cossack, Z. T.",1982,,,0,0,
2933,Clinical and electroencephalographic study on Wilson's disease in children. [Japanese],"Clinical and EEG investigations were performed on 9 children in 8 families with Wilson's disease. The subjects consisted of 4 cases with neurological symptoms, 2 cases with neurological and hepatic symptoms, 2 cases with hepatic symptoms and one asymptomatic case of Wilson's disease. All patients showed low serum ceruloplasmin concentration and increased urinary copper excretion. Behavior and emotional disorders were observed in 5 patients with neurological symptoms (4 cases) and with neurological and hepatic symptoms (one case). At the initial EEG recordings all patients revealed abnormalities of background activity. Anterior theta bursts or 6 c/s wave and spike phantoms were found only in 5 patients who developed behavior and emotional disorders. In clinical and EEG investigation of 5 patients who were followed for more than 5 years, anterior theta bursts and 6 c/s wave and spike phantoms disappeared with improvement of behavior and emotional disorders. The prognosis was good in 4 out of 5 patients who were followed for more than 5 years under the administration of penicillamine, and EEG findings were also improved. These results indicated that the dysfunction of diencephalon was an important contributor to behavior and emotional disorders which were often found during the course of Wilson's disease.",central nervous system;diagnosis;diencephalon;electroencephalography;etiology;major clinical study;oral drug administration;therapy;Wilson disease;ceruloplasmin;penicillamine,"Ichiba, N.;Doi, T.;Ohtahara, S.",1982,,,0,0,
2934,Clinical variability of Wilson's disease. [Italian],,case report;central nervous system;heredity;liver;Wilson disease;penicillamine,"Palmieri, M.;Colombo, A.",1981,,,0,0,
2935,Porphyria cutanea tarda complicating Wilson's disease,A young woman is described in whom symptomatic porphyria cutanea tarda (PCT) developed during copper chelation therapy for Wilson's disease. Termination of ethanol ingestion and oral contraceptive use resulted in cessation of blistering skin lesions and reduction in urinary porphyrin excretion. This is the first recorded coincidence of these two rare hepatic diseases. Therapeutic implications are discussed.,adverse drug reaction;case report;oral drug administration;porphyria cutanea tarda;therapy;Wilson disease;alcohol;diethylstilbestrol;oral contraceptive agent;penicillamine,"Chesney Mc, C. T.;Wardlaw, L. L.;Kaplan, R. J.;Chow, J. F.",1981,,,0,0,
2936,Penicillamine in 1980,,autoimmunity;cystinuria;editorial;rheumatoid arthritis;therapy;Wilson disease;gold;penicillamine;penicillin G;rheumatoid factor,"Wolheim, F. A.",1981,,,0,0,
2937,Wilson-Konovalov cirrhosis. [Bulgarian],"The results from some complex investigations were summed up, electron microscopic includ., of 18 patients with Wilson--Konovalov disease. The dynamic follow up of the patients with a predominantly liver symptomatic justifies, in a considerable part of them, the terminology ""Wilson--Konovalov"" cirrhosis. The mitochondrial changes found suggest disorders in hepatocyte energetic potential. The objectivized manifest or discrete neutral-lipid or phospho-lipid build-ups in the hepatic parenchymal cell suggest multidirectional disorders in lipid metabolism with lysosome participation. The pathogenetic long-term treatment with d-penicillamine substantially improves not only the clinical symptomatics but the remote prognosis of the disease as well.",adolescent;adult;article;cell nucleus;child;electron microscopy;female;human;laparoscopy;liver;liver mitochondrion;male;middle aged;needle biopsy;pathology;ultrastructure;Wilson disease,"Brailski, K.;Damianov, B.",1981,,,0,0,
2938,The inadvisability of neuroleptic medication in Wilson's disease,"The use of neuroleptic drugs in the management of a patient with Wilson's disease was examined from the clinical, pharmacological, and pathophysiological points of view. The weight of evidence suggests that the medication poses a threat to life in patients with this disease because of its masking effects, lack of therapeutic rationale, and adverse reactions. Difficulty in recognizing the biological basis of the behavior disorders and in differentiating between the dementia in the disease and schizophrenic psychosis is associated with the use of inadvisable medication. In order to facilitate early administration of specific treatment, a proper staging of the disease and the criteria for early diagnosis are proposed.",adverse drug reaction;affective neurosis;case report;central nervous system;dementia;drug therapy;gait disorder;low copper diet;oral drug administration;psychosis;schizophrenia;sleep disorder;slurred speech;therapy;tremor;Wilson disease;chlorpromazine;neuroleptic agent;penicillamine;pyridoxine;thioridazine,"Tu, J.",1981,,,0,0,
2939,Attempt of treatment of Wilson's disease with teta. [French],,case report;central nervous system;therapy;Wilson disease;penicillamine;trientine,"Duc, M.;Leichtmann, G. A.;Wiederkehr, P.",1981,,,0,0,
2940,Hepatic copper in primary biliary cirrhosis: Biliary excretion and response to penicillamine treatment,"Excessive hepatic copper accumulation occurs in long-lasting cholestatic liver disorders especially in primary biliary cirrhosis. As in Wilson's disease, penicillamine has recently been introduced for the treatment of primary biliary cirrhosis. In Wilson's there is decreased disease biliary excretion of copper. The present study shows that as compared with controls the biliary excretion of copper is not decreased in primary biliary cirrhosis; instead it may be increased in some patients. However, when compared with high hepatic copper concentration biliary copper excretion was low. In contrast with copper, biliary secretion of bile acids was decreased in eight of the 17 patients. Treatment with oral penicillamine (600 mg/day) for one year resulted in a significant decrease of hepatic copper concentration, but had no consistent effect on the biliary excretion of copper or on the amount of histologically stainable orcein-positive copper-binding protein. The results suggest that excessive hepatic copper accumulation in primary biliary cirrhosis may not be primarily caused by a decreased biliary excretion, or that a new equilibrium is achieved in advanced primary biliary cirrhosis. D-penicillamine appears to improve significantly the biliary excretion of bile acids.",bile secretion;biliary cirrhosis;biliary excretion;drug therapy;liver;liver cirrhosis;major clinical study;primary biliary cirrhosis;therapy;cholecystokinin;copper;glycerol oleate;penicillamine,"Salaspuro, M. P.;Pikkarainen, P.;Sipponen, P.",1981,,,0,0,
2941,Computerized cranial tomography in Wilson disease: Report of a case before and after penicillamine therapy,"A patient with Wilson's Disease presenting neurologic signs was treated with d-Penicillamine. Computerized cranial tomography (CT) performed before therapy showed symmetrical areas of low density in the region of the basal ganglia, enlargement of ventricles, and bilateral increased density of the medial nuclei of the thalamus. This abnormality of the thalamus had not been reported previously in Wilson's disease. After two years' therapy there was an evident clinical improvement and at the same time a reduction of the CT abnormalities. The reports on CT scanning in Wilson's disease are reviewed.",basal ganglion;brain ventricle dilatation;case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;thalamus;Wilson disease;contrast medium;penicillamine,"Lanci, G.;Balottin, U.;Cecchini, A.;Ottolini, A.",1981,,,0,0,
2942,Pemphigus-like mucosal lesions: a side effect of penicillamine therapy,"A patient with Wilson's disease on long-term penicillamine therapy was seen for evaluation and management of chronic persistent debilitating stomatitis, which was subsequently determined to be cytologically and histologically consistent with pemphigus vulgaris. A brief review of the pertinent literature disclosed that the dermatologic lesions of pemphigus secondary to penicillamine are alleviated by discontinuation of penicillamine and institution of prednisone therapy. Our patient's primarily oral lesions did not resolve with this recommended alteration in therapy, since penicillamine could be discontinued only briefly in the interest of maintaining acceptable serum copper levels and because of the paucity of available alternative copper-chelating agents. Eventually the patient was placed on tetraethylene tetramine (TETA), an experimental copper-chelating agent, and betamethasone (Celestone). This has provided a satisfactory reduction in serum copper levels and resolution of the oral lesions.",adverse drug reaction;case report;drug therapy;mouth;oral drug administration;pemphigus vulgaris;skin toxicity;stomatitis;therapy;Wilson disease;ascorbic acid;betamethasone;levamisole;penicillamine;prednisone;tetracycline;trientine,"Eisenberg, E.;Ballow, M.;Wolfe, S. H.",1981,,http://dx.doi.org/10.1016/0030-4220%2881%2990151-1,0,0,
2943,Plasma amine oxidases in Wilson's disease,"Plasma Mono- and Diamine-Oxidase activities (MAO and DAO), two copper containing enzymes, were estimated in 5 patients with Wilson's disease, without treatment and during D-Penicillamine treatment. Ceruloplasmin and 'free' copper plasma levels were simultaneously measured. MAO was elevated in all cases, while DAO was within normal limits. D-Penicillamine administration did not result in significant reductions of these enzyme activities. It is likely that alterations of copper metabolism induced by Wilson's disease and by D-Penicillamine administration do not affect the activity of MAO or DAO. The increase in MAO activity in Wilson's disease probably results from the hepatic fibrosis.",article;case report;ceruloplasmin blood level;copper blood level;drug therapy;etiology;heredity;liver;oral drug administration;pathophysiology;therapy;Wilson disease;amine oxidase (copper containing);amine oxidase (flavin containing);copper;penicillamine;putrescine c 14;radioisotope;unclassified drug,"Bombardieri, G.;Bevilacqua, E.;Conti, L. R.;Innocenti, P.;Perretti, M. A.",1981,,http://dx.doi.org/10.1016/0024-3205%2881%2990279-4,0,0,
2944,Urinary copper excretion and hepatic copper concentration in liver disease,"Urinary copper excretion was found to be increased in patients with cholestasis, hepatitis and cirrhosis, but the penicillamine-induced increment was normal. Wilson's disease patients had increased copper excretion before and after penicillamine, especially in untreated cases. Hepatic copper concentrations correlated with urinary copper excretion in cholestasis and treated Wilson's disease, but not in hepatitis or cirrhosis. In treated Wilson's disease, measurement of urinary copper excretion should be valuable in estimating the degree of removal of copper from the body during therapy. Urinary copper clearances were raised in various liver conditions, maximally in untreated Wilson's disease. It is suggested that only part of the serum non-caerulo plasmin copper is available for excretion into urine.",bile duct;cholestasis;copper liver level;copper urine level;liver;major clinical study;Wilson disease;penicillamine,"Frommer, D. J.",1981,,,0,0,
2945,Wilson's disease: General review. [French],"Wilson's disease is characterized by diffuse deposits of copper throughout the body, responsible for the neuropsychiatric, hepatic and ocular manifestations of the disease. After briefly reviewing copper metabolism the authors describe the various clinical and biological features of Wilson's disease, placing emphasis on the importance of early treatment with D-penicillamine.",central nervous system;diagnosis;drug therapy;etiology;heredity;pathogenesis;review;therapy;Wilson disease;copper;diethyldithiocarbamic acid;dimercaprol;penicillamine;pyridoxine;trientine,"Guerin, J. M.;Lavergne, T.;Tibourtine, O.;Lamotte, M.",1981,,,0,0,
2946,Treatment of Wilson's disease with oral zinc,,abstract report;central nervous system;clinical article;drug therapy;human;liver;therapy;Wilson disease;penicillamine;zinc acetate,"Brewer, G. J.;Prasad, A. S.;Cossack, Z. T.;Rabbani, P. I.",1981,,,0,0,
2947,Penicillamine-induced dermolytic dermatosis in a patient with Wilson's disease. [German],A 29-year-old female patient developed a dermolytic dermatosis after 2 years' treatment with penicillamine for Wilson's disease. The skin lesions were localized on skin areas exposed to trauma. Light and electron microscopic investigations showed alterations of all compartments of connective tissue. Patients under long-term high-dose treatment with penicillamine should be closely monitored for cutaneous and systemic connective tissue disease.,adverse drug reaction;case report;dermatitis;dermatolysis;drug therapy;electron microscopy;histology;oral drug administration;skin disease;therapy;ultrastructure;Wilson disease;penicillamine,"Bardach, H.;Gebhart, W.",1981,,,0,0,
2948,Penicillamine nephropathy,"Treatment with penicillamine for rheumatoid arthritis, Wilson's disease, cystinuria, or lead poisoning may be complicated by damage to the kidneys. In such cases proteinuria usually appears within four to 18 months but occasionally the onset may be later. The incidence of proteinuria is greater in patients with rheumatoid arthritis and cystinuria (30%) than in those with Wilson's disease (4%), and its occurrence is linked with the mean daily dose of penicillamine and the speed with which this maintenance dose is reached. Patients with rheumatoid arthritis who have low serum concentrations of IgG and IgA may be more susceptible, and those with the DRW2 and DWR3 antigens are more likely to react to either penicillamine or gold, perhaps reflecting pharmacological properties common to the two drugs. Penicillamine is a valuable drug in rheumatoid arthritis and may be life saving in Wilson's disease and cystinuria. With appropriate prescribing, the incidence of proteinuria and the nephrotic syndrome may be kept to a minimum and the potential benefits made available to the maximum number of patients.",adverse drug reaction;antigen antibody complex;drug induced disease;editorial;kidney;nephrotic syndrome;nephrotoxicity;proteinuria;rheumatoid arthritis;therapy;Wilson disease;penicillamine,Anonymous,1981,,,0,0,
2949,D-penicillamine in pregnancy - to ban or not to ban?,"The action of D-penicillamine on collagen can cause undesired side-effects in the treatment of cystinuria and Wilson's disease, it is on the other hand essential to the therapy of rheumatoid arthritis and scleroderma. Furthermore D-penicillamine can be potentially teratogenic, since it crosses the placental barrier. From the literature and our own observation of two pregnancies it is shown that among 87 pregnant women who received D-penicillamine 46 cases were treated during the whole period of pregnancy. Two infants from the latter group were found to have severe connective-tissue defects. We suggest that the dose of D-penicillamine in pregnant patients with cystinuria and Wilson's disease should be kept as low as possible. In the case of rheumatoid arthritis D-penicillamine should not be given during pregnancy.",adverse drug reaction;connective tissue disease;cystinuria;pregnancy;therapy;Wilson disease;penicillamine,"Endres, W.",1981,,http://dx.doi.org/10.1007/BF01716453,0,0,
2950,"Pemphigus-like lesions induced by D-penicillamine. Analysis of clinical, histopathological, and immunofluorescence features in 34 cases","Although fraught with numerous adverse side effects, D-penicillamine (beta-beta-dimethylcysteine) is widely used to treat a variety of diseases. Among the most common are rheumatoid arthritis, systemic sclerosis, generalized morphea, psoriatic arthritis, Wilson's disease (hepatolenticular degeneration), and cystinuria. One infrequent complication of the therapy with D-penicillamine is the development of bullae with clinical, histological, and immunological characteristics of forms of pemphigus. The severity of this complication, and its prognosis, course, and treatment, have not always been fully described in published reports. Therefore, we contacted the authors of all case reports about bullous complications of penicillamine for further information about them in follow-up.",adverse drug reaction;bullous dermatitis;cytology;histopathology;immunofluorescence;major clinical study;oral drug administration;pemphigus vulgaris;rheumatoid arthritis;therapy;Wilson disease;penicillamine,"Santa Cruz, D. J.;Marcus, M. D.;Prioleau, P. G.;Uitto, J.",1981,,,0,0,
2951,Ultrastructure of penicillamine-induced skin lesions,"Three cases of D-penicillamine-induced skin lesions, two hemorrhagic and one elastosis perforans serpiginosa (EPS)-like, were examined with the electron microscope. In hemorrhagic lesions elastic fibers were diminished. In EPS lesions elastic fibers were remarkably increased in the papillary and reticular dermis. These appeared bramble bush-like with elastic fiber stains as described by Lund. Ultrastructurally, the bramble bush fibers consisted of near-normal core and abnormal coat which is medium electron-dense and lacks the alternating pattern of dense and light layer of the normal dermal elastic fibers. The 'thorns' were formed as regular swellings of this coating material at regular intervals and at a right angle to the long axis of these fibers. In some fibers the coating material did not encircle the entire circumference of the core, suggesting that it was added upon the normal elastic fiber after the disease process began. Elastic fibers in the perforation canal through the epidermis were either intact bramble bush fiber or degeneration of it. Collagen fibers in both hemorrhagic and EPS lesions were poorly stained with routine electron microscopic stains. The most striking abnormality was an extreme variation of thickness of individual fibers ranging from 0.01 mum to 0.05 mum. Banding patterns and periodicity were normal. Subendothelial separation of vascular endothelial cells in small vessels and actual degeneration of subendothelial elastic fibers (internal elastic membrane) in larger vessels seem to be the basic defect in hemorrhagic lesions. Elastosis perforans serpiginosa seems to be a phenomenon caused by a variety of abnormal elastic fibers. Clearly, the ones in our case are completely different from idiopathic ones. It is assumed that any abnormal elastic fibers which elicit foreign body recognition by the host are commonly eliminated through this phenomenon.",adverse drug reaction;article;bruising;case report;diagnosis;drug eruption;ecchymosis;elastic fiber;elastosis perforans;elastosis perforans serpiginosa;electron microscopy;erythema;oral drug administration;skin;skin bleeding;skin toxicity;ultrastructure;Wilson disease;collagen fiber;griseofulvin;lidocaine;penicillamine;pyridoxine,"Hashimoto, K.;McEvoy, B.;Belcher, R.",1981,,,0,0,
2952,Wilson's disease: seven cases with hepatic onset (author's transl). [Spanish],,adolescent;adult;article;child;female;hepatitis/et [Etiology];human;liver/an [Drug Analysis];liver cirrhosis/et [Etiology];male;pregnancy;pregnancy complication;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];copper/an [Drug Analysis];penicillamine/dt [Drug Therapy],"Pigrau Serrallach, C.;Pahissa Berga, A.;Clotet Sala, B.;Guardia Masso, J.",1981,25 Nov,,0,0,
2953,Dopamine beta-hydroxylase inhibition in a patient with Wilson's disease and manic symptoms,The authors studied the effect of dopamine beta-hydroxylase inhibition on the manic symptoms of a 34-year-old man. They found that fusaric acid decreased the patient's manic symptoms and that his symptoms approximately reverted to their previous state when a placebo was reinstituted.,adult;case report;central nervous system;drug therapy;enzyme inhibition;mania;psychological aspect;therapy;Wilson disease;dopamine beta monooxygenase;fusaric acid;haloperidol;penicillamine;placebo,"Pandey, R. S.;Sreenivas, K. N.;Patil, N. M.;Swamy, H. S.",1981,,,0,0,
2954,Clinical characteristics of Wilson's disease in childhood with special reference to fulminant form,"Clinical manifestations of Wilson's disease in childhood were analyzed according to age groups. Hepatic symptoms were predominant in patients under the age of 10, and cerebral symptoms became predominant thereafter. Kayser-Fleischer rings gradually appeared after 5 years. Tremor, hematemesis from esophageal varices, and epileptic seizures were not observed under the age of 10. Acute onset of hepatic failure associated with severe hemolytic crisis is the most dangerous course of the disease. Characteristically, remarkable hypercupremia, hypercupruria, increased serum direct bilirubin, rapidly progressive anemia with reticulocytosis and high S-GOT levels preceded hepatic coma and ascites. Exchange transfusion as well as early start of penicillamine therapy could induce complete recovery. Experimental studies indicated a marked inhibitory effect of histidine, SH containing amino acids, human plasma as well as penicillamine on copper-induced hemolysis.",age;congenital disorder;diagnosis;hemolytic anemia;kayser fleischer ring;liver;short survey;therapy;visual system;Wilson disease;copper;penicillamine,"Arima, M.;Aoki, T.",1981,,,0,0,
2955,Wilson's disease. [German],"Wilson's disease is a rare congenital disorder of the copper metabolism with an autosomal recessive heredity. Early diagnosis is possible by familial investigation, ceruloplasmin assay and demonstration of raised cupriuria. Early treatment with copper chelators causes significant improvement of this thesaurismosis, which formerly was fatal in most cases.",central nervous system;diagnosis;etiology;liver;pathogenesis;short survey;therapy;visual system;Wilson disease;ceruloplasmin;copper chloride cu 64;copper chloride cu 65;penicillamine;potassium sulfide;pyridoxine;radioisotope;unclassified drug,"Stremmel, W.;Strohmeyer, G.",1981,,,0,0,
2956,Possible errors in sampling percutaneous liver biopsies for determination of trace element status: Application to patients with primary biliary cirrhosis,"A growing use is being made of percutaneous liver biopsies for trace element analysis, especially of iron in case of haemochromatosis and of copper in case of Wilson's disease and primary biliary cirrhosis (PBC). Various authors warn against the risks of contamination of the sample with trace elements, especially by the needle; positive errors of up to 30% for copper and up to 10% for zinc have been reported. Furthermore, the variability of the copper distribution, especially in cirrhotic livers, also may be a cause of erroneous results: the copper may be unevenly distributed within the tissues, e.g. as a result of variable amounts of fibrous tissue. To test this last problem duplicate samples were taken with the Tru-cut needle from 50 patients, who met certain clinical criteria of PBC (including positive antimitochondrial antibody test, increased alkaline phosphatase, raised serum IgM and a normal extrahepatic cholangiogram).",contamination;diagnosis;human cell;in vitro study;liver;liver biopsy;major clinical study;primary biliary cirrhosis;copper;iron;trace element,"Nooijen, J. L.;Van Den Hamer, C. J. A.;Houtman, J. P. W.;Schalm, S. W.",1981,,http://dx.doi.org/10.1016/0009-8981%2881%2990288-6,0,0,
2957,Late onset of Wilson's disease. Report of a family,"Five cases of Wilson's disease were diagnosed in a family of eight silings. All of them had Kayser-Fleischer rings. The first neurologic symptoms appeared in one person at age 46 yrs; in another, psychotic symptoms appeared at age 38 yrs; and in one patient, jaundice was noted at age 40 yrs. Two other persons, aged 53 and 43 yrs, were still without hepatic, neurologic, or psychiatric symptoms of the disease at the time of writing. The family described is very atypical with regard to the age at onset of Wilson's disease.",central nervous system;diagnosis;familial incidence;jaundice;liver;mental disease;onset age;oral drug administration;sibling;therapy;Wilson disease;penicillamine,"Czlonkowska, A.;Rodo, M.",1981,,,0,0,
2958,Treatment of hepatocerebral dystrophy (Wilson-Westphal-Konovalov's disease). [Russian],,article;diet therapy;drug combination;drug screening;human;Wilson disease/dt [Drug Therapy];amino acid/dt [Drug Therapy];cerebrolysin;ceruloplasmin/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];unithiol/dt [Drug Therapy],"Lekar, P. G.;Makarova, V. A.;Botvinnik, V. S.",1981,,,0,0,
2959,Disorders affecting the basal ganglia. [French],,adverse drug reaction;akinesia;autonomic nervous system;basal ganglion;brain metabolism;central nervous system;extrapyramidal syndrome;hemiballism;muscle;muscle rigidity;parkinsonism;progressive supranuclear palsy;review;Shy Drager syndrome;tremor;Wilson disease;amantadine;benserazide;benserazide plus levodopa;benzodiazepine derivative;brain monoamine;bromocriptine;bromocriptine mesilate;carbidopa;carbidopa plus levodopa;cholinergic receptor blocking agent;levodopa;monoamine oxidase inhibitor;neuroleptic agent;penicillamine;piribedil;pyridoxine,"Davous, P.",1981,,,0,0,
2960,Plasma non-ceruloplasmin copper in hepatocerebral dystrophy (criterion for the diagnosis and evaluation of cuprogogue therapy). [Russian],Results of determining the plasma levels of non-coeruloplasmin copper in 29 patients with hepatocerebral dystrophy (before and during cuprogogue therapy) and in 15 practically healthy individuals are presented. A statistically significant rise of this level (as compared with that in the control group) was revealed in the patients with Wilson-Konovaloff's disease. The clinical improvement of the patients with hepatocerebral dystrophy was accompanied by normalization of the plasma level of non-coeruloplasmin copper. This gives one grounds to conclude that this parameter can be used as a criterion for evaluating the efficacy of the treatment given.,article;blood;human;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Botvinnik, V. S.;Lekar, P. G.;Makarova, V. A.",1981,,,0,0,
2961,Liver copper analysis after long-term treatment of Wilson's disease with D-penicillamine. [German],"Abundant copper storage is the leading pathogenic principle in the recessive autosomal Morbus Wilson. This leads to organ lesions which particularly affect the CNS and the Liver (copper intoxication theory). Early diagnosis and family investigation are necessary requirements. Chemical copper determination of the liver, for which only 2 mg liver tissue is required, has become a familiar diagnostic parameter. Liver cirrhoses in children and adolescents should be suspected until their absence has been proven. The therapy consists of permanent treatment with DPA; no other drug will do. As a rule, the liver copper value will reduce as a result of the therapy.",copper liver level;drug therapy;liver;liver biopsy;review;therapy;Wilson disease;copper;penicillamine,"Lange, J.;Brandt, G.",1981,,,0,0,
2962,Clinical features and treatment of Wilson's disease. [Hungarian],,central nervous system;clinical study;drug therapy;liver;major clinical study;therapy;visual system;Wilson disease;baclofen;calcium sulfide;clonazepam;clozapine;diazepam;levodopa;metixene;myoflexin;penicillamine;probenecid;unclassified drug,"Baraczka, K.;Szegedy, L.;Kenez, J.;Schaff Semmelweis Semmelwis Orvostud. Egyet. Psychiat. Klin.. Budapest, Z.",1980,,,0,0,
2963,Wilson's disease: Experience with long term d-penicillamine therapy,,drug therapy;liver;major clinical study;oral drug administration;therapy;Wilson disease;copper;penicillamine,"Batey, R.;Kirk, A.;Sherlock, S.",1980,,,0,0,
2964,Treatment of Wilson's disease with triethylene tetramine dihydrochloride. A case report,"Wilson's disease is an autosomal recessive disorder characterized by progressive cirrhosis or neurological signs. Early detection and prompt treatment can reverse the relentless course of the disease. Treatment with D-penicillamine substantially improves the outlook for such patients unless undesirable side effects preclude its use. We report the use of triethylene tetramine dihydrochloride (Trien), a new non-sulfhydryl-chelating agent, in a girl who was unable to tolerate D-penicillamine in spite of steroid coverage. The drug has been well tolerated without side effect for approximately 2 1/2 years. Our patient's favorable clinical response would suggest that Trien is a safe alternative agent for the treatment of Wilson's disease when D-penicillamine is not tolerated.",adolescent;autosomal recessive inheritance;case report;clinical study;drug therapy;liver;therapy;Wilson disease;penicillamine;prednisone;trientine,"Haslam, R. H. A.;Sass-Kortsak, A.;Stout, W.;Berg, M.",1980,,,0,0,
2965,"Wilson's disease: Physiopathology, clinic and therapeutic. [Italian]",,central nervous system;diagnosis;drug therapy;etiology;heredity;kidney;liver;pathophysiology;review;short survey;therapy;Wilson disease;amantadine;dimercaprol;edetate calcium;levodopa;methylprednisolone;penicillamine;potassium sulfide;prednisone;trientine;unclassified drug,"Cunego, A.;Chiauzzi, R.;De Luca, D.",1980,,,0,0,
2966,Investigations concerning Wilson's disease in the GDR. Part II: Pathogenesis and clinic. [German],"For the performance of life-saving long-term therapy in Wilson's disease, diagnosis must be early. The preclinical (asymptomatic) and clinical stages are described in detail, including the various forms of manifestation, and their differential diagnosis.",diagnosis;etiology;liver;therapy;Wilson disease;penicillamine,"Loessner, J.;Bachmann, H.;Biesold, D.",1980,,,0,0,
2967,Penicillamine-induced pemphigus,"The first case of penicillamine-induced pemphigus in a patient with Wilson's disease was reported by Degos et al in 1969. This was followed by many other reports of pemphigus (usually foliaceus or erythematosus), occurring mainly in patients treated with penicillamine for rheumatoid arthritis (RA). We present here a case of pemphigus vulgaris in a woman of 50, probably induced by penicillamine that affected only the oral mucosa.",adverse drug reaction;case report;cytology;diagnosis;drug eruption;histology;mouth;mouth mucosa;pemphigus vulgaris;penicillamine,"Trau, H.;Schewach-Millet, M.;Gold, I.",1980,,http://dx.doi.org/10.1001/archderm.116.6.721,0,0,
2968,Penicillamine: Twenty-five years later,,cystinuria;editorial;immunopathology;joint;rheumatoid arthritis;therapy;Wilson disease;penicillamine,Anonymous,1980,,,0,0,
2969,Wilson's disease and hemochromatosis. [German],"The copper storage disease known as Wilson's disease, and the iron storage disease idiopathic hemochromatosis are genetically determined conditions. The liver cells are those first affected and later other organ systems are implicated. In this way the typical syndromes arise. In spite of the copious literature of recent years, the early diagnosis is often not made. Thus valuable time for the therapy is lost, which is particularly deleterious for Wilson's disease. This therapy consists of removal of copper by long-term treatment with D penicillamine, cutting down of copper supply via the intestine, and prescription of the anti-absorption agent potassium sulphide in Wilson's disease as in the blood letting in idiopathic hemochromatosis. In it treatment with complex former desferriozamine is often omitted. The earlier the treatment is begun, the better are the clinical results. Family screenings for asymptomatic cases are urgently necessary, especially in Wilson's disease as the therapy hinders the clinical manifestations when it is begun at this stage.",blood and hemopoietic system;central nervous system;drug therapy;hemochromatosis;liver;liver disease;short survey;therapy;Wilson disease;copper;deferoxamine;deferoxamine mesylate;penicillamine,"Lange, J.",1980,,,0,0,
2970,Penicillamine-induced myasthenia gravis in progressive systemic sclerosis,"Penicillamine promotes the excretion of copper, lead, mercury, and cystine. It has long been used in the treatment of Wilson's disease, lead and mercury intoxication, and cystinuria. It has been used extensively in the management of rheumatoid arthritis (RA) since 1965 and in progressive systemic sclerosis (PSS). Numerous side effects may develop in patients receiving penicillamine, including autoimmune disorders such as systemic lupus erythematosus, pemphigus, Goodpasture's syndrome and polymyositis. Recently several patients who developed unequivocal myasthenia gravis (MG) have been reported. The majority of patients with penicillamine-induced MG and RA, but 2 patients with Wilson's disease have also been reported. We present a patient with PSS who developed a reversible myasthenia gravis during treatment with penicillamine.",adverse drug reaction;autoimmune disease;case report;drug therapy;muscle;myasthenia gravis;oral drug administration;scleroderma;therapy;edrophonium;penicillamine;penicillin G;pyridostigmine,"Torres, C. F.;Griggs, R. C.;Baum, J.;Penn, A. S.",1980,,,0,0,
2971,Cutaneous side effects due to D-penicillamine treatment in hepatocerebral degeneration (Wilson's disease). [German],,adverse drug reaction;soft tissue;Wilson disease;penicillamine,"Jacobi, H.;Kunath, B.",1980,,,0,0,
2972,Treatment of Wilson's disease. A report on 30 cases. [French],"Therapy is based on the use of penicillamine, which should be administered very progressively in the initial stages. The usual dosage is 1.5 to 2 g/day initially, followed by a maintenance dose of 1 to 1.5 g/day, which should be continued for an indefinite period. Neurological clinical signs progressed favourably in 21 out of 24 patients. Of 18 cases with advanced hepatic affection, 2 died from increasing liver damage after 5 and 15 years of treatment, and 3 of the 8 patients with initial severe cirrhosis died within less than one year after starting treatment with the chelator. The Kayser-Fleischer ring had disappeared in 11 of the patients after an average period of 5 years. Hematological and rheumatological manifestations were not influenced by the treatment. Three pregnancies had successful outcomes. The iatrogenic effects of treatment, at an early stage, were: worsening of neurological signs (4 cases) or thrombopenia (3 cases), severe allergic reactions (2 cases), and one case of epileptic seizures. It appears essential to prevent these accidents. At a later stage, 5 nephropathies, one case of pemphigus and 2 cases of lupus erythematosus were observed. Though the complications of penicillamine therapy represent a very important practical problem, the serious nature of the spontaneous progression of Wilson's disease justifies taking this therapeutic risk. The prognosis depends upon the extent of neurological and especially hepatic lesions. Early diagnosis is therefore of primary importance.",central nervous system;drug therapy;heredity;liver cirrhosis;therapy;visual system;Wilson disease;penicillamine;trientine,"Pepin, B.;Goldstein, B.;Lidy, C.",1980,,,0,0,
2973,Investigations of Wilson's disease in the GDR. Part III: Diagnosis and therapy. [German],"Taking into consideration the manifold symptomatology of Wilson's disease on the one hand and the necessity of an early - possibly possible already at the asymptomatic stage before the 6th year of life - diagnostic ascertainment on the other hand, the diagnostic approach performed in the GDR is described. Furthermore, the directives of treatment and the successes of treatment are discussed as well as the various side-effects of the D-penicillamine therapy described, in which case the severe nephrotic syndromes are particularly considered.",adverse drug reaction;article;blood and hemopoietic system;cheilosis;diagnosis;digestive system;drug therapy;fever;gastrointestinal symptom;kidney;leukopenia;nephrotoxicity;oral drug administration;proteinuria;rash;taste;therapy;thrombocytopenia;Wilson disease;copper;penicillamine;potassium sulfide;pyridoxine;unclassified drug,"Lossner, J.;Storch, W.;Bachmann, H.",1980,,,0,0,
2974,Neuropsychiatric metabolic disorders. III. Vitamins and trace elements. [German],,beriberi;central nervous system;drug therapy;etiology;extrapyramidal system;metabolic disorder;oral drug administration;pyridoxine deficiency;short survey;therapy;Wilson disease;copper;cyanocobalamin;cysteine;folic acid;iron;manganese;penicillamine;pyridoxine;thiamine,"Kanig, K.",1980,,,0,0,
2975,Disordered esophageal motility in Wilson's disease,"The authors describe the manometric findings in a patient with hepatolenticular degeneration (Wilson's disease). After 21 years of penicillamine therapy, one of the principal neurological problems remaining in a 49-yr-old white man with Wilson's disease is food-induced dysphagia. Barium contrast studies showed gross incoordination of the upper esophagus; the manometric study revealed dysmotility of the mid and distal esophagus.",case report;diagnosis;esophagus;esophagus motility;heredity;liver;manometry;therapy;Wilson disease;penicillamine,"Haggstrom, G.;Hirschowitz, B. I.",1980,,,0,0,
2976,Metallothionein: A natural 'antitoxin' for heavy metals. [Dutch],,drug analysis;drug industry;drug interaction;human;human cell;in vitro study;kidney;liver;preliminary communication;theoretical study;Wilson disease;cadmium;heavy metal;metallothionein;zinc sulfate,"Reedijk, J.",1980,,,0,0,
2977,Immunological investigations by means of the lymphocyte transformation test on side-effects of the D-penicillamin therapy in Wilson's disease. [German],,adverse drug reaction;drug therapy;immunopathology;joint;kidney;lymphocyte transformation test;oral drug administration;proteinuria;therapy;Wilson disease;penicillamine,"Storch, W.;Berger, H.",1980,,,0,0,
2978,Accommodation defect in Wilson's disease,A 22-year-old man with Wilson's disease had blurred vision caused by a defect of accommodation that we believed to be supranuclear in origin.,accommodation;article;case report;central nervous system;drug therapy;therapy;visual impairment;visual system;Wilson disease;penicillamine;potassium sulfide;pyridoxine;unclassified drug,"Klingele, T. G.;Newman, S. A.;Burde, R. M.",1980,,,0,0,
2979,Wilson's disease or liver cirrhosis of a different etiology. [German],,adolescent;article;blood;case report;cornea disease/et [Etiology];differential diagnosis;female;human;liver/an [Drug Analysis];liver cirrhosis/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;copper/an [Drug Analysis];penicillamine/dt [Drug Therapy],"Kuntz, H. D.;May, B.;Ulmer, W. T.",1979,16 Nov,,0,0,
2980,Serious side effects with D-penicillamine therapy for Wilson's disease. [German],"Immunocomplex nephritis as one of the serious side-effects is dealt with on the basis of 41 patients with Wilson's Disease who have been treated for many years and were stabilised on D-penicillinamine. In one quarter of the patients, proteinuria was found 1 to 5 years after the beginning of the therapy. Until now, an immunocomplex nephritis with diffuse granular, mainly epimembranous IgG and C3 deposits on the glomerular basement membran was found in four patients. No circulating antibodies against cell nuclei were found. The finding of immunocomplex nephritis calls for the discontinuation of the therapy for an at present unknown period of time.",article;basement membrane;chemically induced disorder;glomerulonephritis;glomerulus;human;immune complex disease;immunology;proteinuria;Wilson disease/dt [Drug Therapy];complement component C3/an [Drug Analysis];immunoglobulin A/an [Drug Analysis];immunoglobulin G/an [Drug Analysis];immunoglobulin M/an [Drug Analysis];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Storch, W.;Lossner, J.;Ruchholtz, U.",1979,Sep,,0,0,
2981,Some problems of Wilson's disease. [German],"The Leipzig Center for Wilson's Disease in the GDR is charged with the registration and diagnosis of all homozygous Wilson gene carriers, the clarification of all suspected cases, including the heterozygote test, and the co-ordination of long-term treatment. At present, there are 78 recorded Wilson gene carriers living. On the basis of our own comprehensive observations and investigations over prolonged periods of time, questions concerning pathogenesis, genetics, diagnosis and therapeutic measures, including their side-effects, are dealt with.",adolescent;adult;article;child;genetics;German Democratic Republic;heterozygote detection;homozygote;human;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Lossner, J.;Bachmann, H.;Biesold, D.;Gunther, K.;Ruchholtz, U.;Storch, W.;Wagner, A.",1979,Sep,,0,0,
2982,Checking of urinary copper in patients with Wilson's disease during treatment with D-penicillamine. [Italian],,adolescent;adult;article;atomic absorption spectrometry;female;human;urine;Wilson disease/dt [Drug Therapy];copper/an [Drug Analysis];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Indaco, A.;Pellegrino, L.;Campanella, G.",1979,,,0,0,
2983,Evolution of nocturnal sleep in a case of Wilson's disease. [Italian],,adolescent;article;basal ganglion;case report;drug effect;female;human;pathophysiology;sleep stage;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology],"Ferrari, E.;Puca, F. M.;Specchio, L. M.;Perniola, T.;Leomanni, R.",1979,,,0,0,
2984,Treatment of Wilson's disease using triethylenetetramine dihydrochloride (TETA). [Czech],,adult;article;female;human;male;technique;Wilson disease/dt [Drug Therapy];ethylenediamine derivative/dt [Drug Therapy];trientine/dt [Drug Therapy],"Hauftova, D.;Korbel, J.;Jancik, F.;Kuhr, I.;Ferenc, M.",1978,Dec,,0,0,
2985,Immune deficiency during D-penicillamine treatment. [French],,case report;chemically induced disorder;child;dysgammaglobulinemia;female;human;letter;Wilson disease/dt [Drug Therapy];immunoglobulin A;penicillamine/ae [Adverse Drug Reaction],"Michel, F. B.;Bousquet, J.;Robinet-Levy, M.;Mary, P.",1977,12 Nov,,0,0,
2986,Electrophysiological changes of the brain in Wilson's disease under D-penicillamine treatment. [Japanese],,article;child;electroencephalography;human;male;pathophysiology;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Fujita, T.;Fujita, H.;Okawa, M.;Yokoi, S.",1976,May,,0,0,
2987,T-rosette test in Wilson's disease. [Polish],"Twenty-three patients with Wilson's disease were studied. Using the rosette formation test it was found that the count of T-lymphocytes in the peripheral blood of these patients (29,77% +/- 12,58) was lower than in the control group (61,68% +/- 13,14). Using skin tests for demonstration of delayed hypersensitivity it was noted that in the group of patients the frequency of positive reaction with Candida albicans antigen was lower and these patients showed also less frequently positive reactions after DNCB immunization. The obtained results indicate that in Wilson's disease the functions of T-lymphocytes are distrubed. This may be the cause of previously observed hyperactivity of B-lymphocytes.",adolescent;adult;article;B lymphocyte;Candida albicans;child;delayed hypersensitivity;human;immune adherence;immunology;liver;middle aged;T lymphocyte;Wilson disease/dt [Drug Therapy];fungus antigen/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Czlonkowska, A.",1975,1975,,0,0,
2988,Penicillamine and other therapeutic methods in the treatment of Wilson's disease. [Polish],,allotransplantation;article;human;liver transplantation;nephrotic syndrome/et [Etiology];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];ethylenediamine derivative/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Czlonkowska, A.;Czlonkowski, A.",1975,1975,,0,0,
2989,Complex medical and surgical treatment of hepatolenticular degeneration. [Russian],,adult;article;brain stem;electrostimulation;female;genetics;heterozygote;human;male;mesencephalon;pedigree;thalamus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy],"Bondarchuk, A. N.;Borodkin, I. S.;Vakharlovskii, V. G.;Neifakh, S. A.;Smirnov, V. M.",1975,1975,,0,0,
2990,Pigment cirrhosis of the liver. I. Wilson's disease--hepatolenticular degeneration. [Polish],,article;electron microscopy;feces/an [Drug Analysis];genetics;heterozygote;homozygote;human;liver;metabolism;ultrastructure;urine;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Koziolowa, H.;Dziezbicka, E.",1975,Nov,,0,0,
2991,Experiences with penicillamine in Wilson's disease. [German],"Reports are being made on the principles of treatment of morbus Wilson with the help of seventeen patients and two persons in the pre-clinical stage (asymptomatic). Treatment should be begun as soon as possible in the asymptomatic stage. On the whole the pseudo-sclerosis symptoms react more favourably to treatment than many hypokinetic symptoms. A continuous course of treatment with penicillamine still effects a disappearance of the symptoms even after three to four years. Since evidence of a negative copper balance is widely used in determining the amount of the penicillamine dosage, the measurement of basal copper secretion and copper secretion with the use of penicillamine is discussed as a useful criterion.",adolescent;adult;article;child;female;follow up;human;male;urine;Wilson disease/dt [Drug Therapy];copper;penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Lossner, J.;Bachmann, H.;Eichner, B.",1975,,,0,0,
2992,Acute hemolysis in morbus Wilson (author's transl). [German],,adolescent;adult;article;ascites/dt [Drug Therapy];blood;blood clotting test;blood transfusion;erythrocyte;genetics;hemolytic anemia/et [Etiology];human;liver cirrhosis/et [Etiology];male;protein electrophoresis;urine;Wilson disease/co [Complication];bilirubin;ceruloplasmin;copper;furosemide/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Furrer, H. U.;Tonz, O.",1974,,,0,0,
2993,Introduction. Symposium on copper metabolism and Wilson's disease,,blood;consanguinity;diet therapy;genetics;human;metabolism;motor dysfunction/et [Etiology];pathology;review;United States;urine;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/th [Therapy];ceruloplasmin;copper;dimercaprol/dt [Drug Therapy];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Goldstein, N. P.;Owen Jr, C. A.",1974,Jun,,0,0,
2994,Therapy and rehabilitation of Wilson's disease (author's transl). [Spanish],,adult;article;female;human;male;Wilson disease/dt [Drug Therapy];Wilson disease/rh [Rehabilitation];penicillamine/dt [Drug Therapy],"Eichner, B.;Lossner, J.;Bachmann, H.;Diessner, H.;Biesold, D.;Gunther, K.",1974,Nov,,0,0,
2995,Long-term D-penicillamine therapy of Wilson's disease in childhood. Changes in blood coagulation and effects on the haematopoetic system. [German],,adolescent;article;blood clotting;chemically induced disorder;child;drug effect;female;genetics;hematopoiesis;human;long term care;male;nephrotic syndrome;pedigree;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology],"Hayek, H. W.;Schnack, H.;Widhalm, S.",1973,23 Feb,,0,0,
2996,D-penicillamine. [French],,article;cystinuria/dt [Drug Therapy];human;rheumatoid arthritis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Sternlieb, I.",1973,,,0,0,
2997,Dermatological complications during treatment of Wilsons disease with D-penicillamine. [French],,adolescent;adult;agammaglobulinemia;article;chemically induced disorder;drug eruption;female;human;systemic lupus erythematosus;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Rimbaud, P.;Mirouze, J.;Mary, P.;Meynadier, J.",1973,,,0,0,
2998,"Presymptomatic Wilson's disease. Diagnosis, therapy and family examination. [German]",,adolescent;article;blood;child;enzymology;female;genetics;human;liver/an [Drug Analysis];male;urine;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase;aspartate aminotransferase;ceruloplasmin/an [Drug Analysis];copper/an [Drug Analysis];immunoglobulin;iron;penicillamine/dt [Drug Therapy];plasma protein,"Schmid-Ruter, E.;Feist, D.;Wesch, H.;Rossner, J. A.;Scharer, K.",1973,14 Sep,,0,0,
2999,Favorable results with an association of L-dopa and amantadine added to penicillamine in the treatment of Wilson's disease. [Italian],,adolescent;article;drug potentiation;female;human;Wilson disease/dt [Drug Therapy];amantadine/ad [Drug Administration];amantadine/dt [Drug Therapy];DOPA/ad [Drug Administration];DOPA/dt [Drug Therapy];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Berio, A.;Vento, R.;Di Stefano, A.",1973,19 May,,0,0,
3000,"Detection of asymptomatic and preclinical forms of Wilson's disease by means of a test with 5,5-diphenylhydantoin (hydantoin Polfa). [Polish]",,article;biosynthesis;human;oral drug administration;technique;urine;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;diagnostic agent;penicillamine/dt [Drug Therapy];phenytoin/ad [Drug Administration],"Pakszys, W.",1973,1973,,0,0,
3001,Principles of the pathogenetic therapy of congenital extrapyramidal diseases. [Russian],,adolescent;adult;article;chronic disease;extrapyramidal syndrome/cn [Congenital Disorder];extrapyramidal syndrome/dt [Drug Therapy];female;Hallervorden Spatz disease/dt [Drug Therapy];human;hyperkinesia/dt [Drug Therapy];male;Parkinson disease/dt [Drug Therapy];Wilson disease/cn [Congenital Disorder];Wilson disease/dt [Drug Therapy];atropine/dt [Drug Therapy];chelating agent/dt [Drug Therapy];DOPA/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenothiazine derivative/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];thiol derivative/dt [Drug Therapy];trifluoperazine/dt [Drug Therapy];tropane derivative/dt [Drug Therapy],"Tkachev, R. A.;Markova, E. D.;Gotovtseva, E. V.;Barkhatova, V. P.;Ivanova-Smolenskaia, I. A.",1973,,,0,0,
3002,"Wilson's disease in Switzerland. Clinical, genetic and biochemical studies. [German]",,article;cytochemistry;female;genetics;human;liver/an [Drug Analysis];male;metabolism;Switzerland;urine;Wilson disease/di [Diagnosis];Wilson disease/ep [Epidemiology];copper;diagnostic agent;penicillamine,"Tschumi, A.;Colombo, J. P.;Moser, H.",1973,27 Jan,,0,0,
3003,Current treatment of hepatolenticular degenerescence. [Romanian],,article;diet therapy;human;Wilson disease/th [Therapy];corticosteroid/dt [Drug Therapy];cysteine/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];edetic acid/dt [Drug Therapy];folic acid/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Faur, A.;Pasculescu, G.;Dorl, F.",1972,Dec,,0,0,
3004,Therapeutic use of d-penicillamine. [Polish],,basement membrane;biosynthesis;cystinuria/dt [Drug Therapy];drug effect;hematopoiesis;human;kidney;metabolism;review;rheumatoid arthritis/th [Therapy];systemic sclerosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];collagen;copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Bogdanikowa, B.",1972,9 Oct,,0,0,
3005,Cutis hyperelastica following prolonged administration of penicillamine in a patient with Wilson's disease. [French],,adolescent;article;biopsy;blood;chemically induced disorder;Ehlers Danlos syndrome;female;human;pathology;skin disease;Wilson disease/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Charlebois, G.;Cadotte, M.;Barbeau, A.",1972,May,,0,0,
3006,Long-term therapy of liver diseases. [German],,aged;chronic disease;diet therapy;fatty liver/dt [Drug Therapy];female;hemochromatosis/dt [Drug Therapy];hepatic encephalopathy/dt [Drug Therapy];hepatitis/dt [Drug Therapy];human;liver cirrhosis/dt [Drug Therapy];liver disease/dt [Drug Therapy];liver disease/th [Therapy];liver tumor/dt [Drug Therapy];long term care;male;metastasis;middle aged;parasitic liver disease/dt [Drug Therapy];porphyria/dt [Drug Therapy];review;Wilson disease/dt [Drug Therapy];anabolic agent/dt [Drug Therapy];cortisone/dt [Drug Therapy];fluorouracil/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Markoff, N.",1972,12 Feb,,0,0,
3007,Optic neuritis in a child with Wilson's disease. [German],,adolescent;article;chemically induced disorder;drug effect;human;long term care;male;metabolism;optic nerve atrophy/et [Etiology];optic neuritis/co [Complication];optic neuritis/di [Diagnosis];optic neuritis/dt [Drug Therapy];optic neuritis/et [Etiology];visual acuity;visual field;vitamin deficiency/co [Complication];Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];pyridoxine/ad [Drug Administration],"Damaske, E.;Althoff, W.",1972,Feb,,0,0,
3008,"Wilson's disease. Etiopathogenetic, morphologic, clinical and therapeutic considerations, Case report. [Italian]",,adolescent;article;brain;human;liver;male;pathology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];penicillamine/dt [Drug Therapy],"Mancosu, M.;Bottino, D.;Previati, G.;Pighini, A.;Valli, F.;Colombo, B.",1972,31 Mar,,0,0,
3009,Pregnancy in a case of Wilson's copper metabolism disorder. [German],,amenorrhea/et [Etiology];article;case report;female;human;infertility/et [Etiology];male;pregnancy;pregnancy complication/di [Diagnosis];Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Stahler, E.;Stahler, F.;Sturm, G.",1972,Jul,,0,0,
3010,Wilson's disease. [Czech],,adult;article;female;human;male;metabolism;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Blehova, B.;Heyrovsky, A.;Nebudova, J.",1972,,,0,0,
3011,EEG changes under sodium diethyldithiocarbamate therapy in 2 cases of Wilson's disease. [German],,adult;article;blood;chemically induced disorder;cognitive defect;electroencephalography;female;human;pathophysiology;urine;Wilson disease/dt [Drug Therapy];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];thiocarbamic acid derivative/ae [Adverse Drug Reaction];thiocarbamic acid derivative/dt [Drug Therapy],"Lang, H. D.;Reichenmiller, H. E.;Tigges, F. J.;Braun, H. J.;Golisch, G.",1972,30 Jun,,0,0,
3012,Verruciform perforating elastoma in a patient treated by penicillamine for Wilson's disease. [French],,adult;article;biopsy;chemically induced disorder;cytochemistry;Darier disease;elastic tissue;female;human;metabolism;staining;Wilson disease/dt [Drug Therapy];collagen;penicillamine/ae [Adverse Drug Reaction],"Guilaine, J.;Benhamou, J. P.;Molas, G.",1972,,,0,0,
3013,Possible accidents due to penicillamine during treatment of Wilson's disease. [French],,acute kidney failure;adolescent;adult;article;chemically induced disorder;child;epilepsy;female;human;lupus vulgaris;male;thrombocytopenia;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Boudin, G.;Pepin, B.",1972,May,,0,0,
3014,Abnormalities of the physiology of copper in Wilson's disease. I. The whole-body turnover of copper,,adolescent;adult;article;ascites;blood;child;female;genetics;human;liver;liver cirrhosis;male;metabolism;Taiwan;United States;urine;Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];ceruloplasmin;copper;penicillamine/dt [Drug Therapy];radioisotope,"O'Reilly, S.;Strickland Jr, G. T.;Weber, P. M.;Beckner, W. M.;Shipley, L.",1971,May,,0,0,
3015,Lupus erythematosus due to penicillamine associated with Wilson's disease. [French],,adult;article;chemically induced disorder;female;human;systemic lupus erythematosus;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Boudin, G.;Pepin, B.;Godeau, P.;Vernant, J. C.;Gouerou, H.",1971,Feb,,0,0,
3016,Lupoid syndrome due to D-penicillamine associated with Wilson's disease: clinical study of a case. [French],,adult;article;chemically induced disorder;female;human;lupus vulgaris;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Caille, B.;Harpey, J. P.;Lejeune, C.;Sudre, Y.;Turpin, R.",1971,Feb,,0,0,
3017,Lupoid syndrome due to D-penicillamine associated with Wilson's disease: immunologic study by leukocyte migration test (L.M.T.). [French],,article;cell motion;chemically induced disorder;drug eruption/et [Etiology];female;human;immunology;leukocyte;lupus vulgaris;male;technique;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Harpey, J. P.;Moulias, R.;Goust, J. M.;Berthaux, P.",1971,Feb,,0,0,
3018,On hepatolenticular degeneration (Wilson's disease). 3. Hepatic localization of Cu64: scintigraphic and dynamic study before and after treatment with BAL and D-penicillamine. [Italian],,adolescent;article;blood;female;human;kidney;liver;liver function test;male;metabolism;scintiscanning;Wilson disease/dt [Drug Therapy];copper;dimercaprol/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"D'Addabbo, A.;Damato, V. D.;Germinario, L.;Campanella, G.;Boccuni, N.",1971,1971,,0,0,
3019,Penicillamine in the treatment of scleroderma. Lathyrogenic drugs. [Polish],,chemically induced disorder;chemistry;citric acid cycle;human;lathyrism;metabolism;review;systemic sclerosis/dt [Drug Therapy];time;Wilson disease/dt [Drug Therapy];chelating agent/pd [Pharmacology];collagen;copper;hydroxyproline;penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy],"Szczepanski, A.",1971,1971,,0,0,
3020,On hepatolenticular degeneration (Wilson's disease). II. Treatment of 2 cases of Wilson's disease for 8 months with D-penicillamine. [Italian],,adolescent;article;female;human;male;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Germinario, L.;Campanella, G.;D'Addabbo, A.",1971,1971,,0,0,
3021,Diagnosis of asymptomatic forms of hepatolenticular degeneration. [Czech],,adolescent;article;biopsy;blood;dermatoglyphics;female;genetics;heterozygote;homozygote;human;liver disease;metabolism;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/an [Drug Analysis];copper;penicillamine/dt [Drug Therapy],"Kuncova, Z.;Dittrich, J.;Nevsimalova, S.;Marecek, Z.;Heyrovsky, A.",1971,Apr,,0,0,
3022,Use of neutron activation analysis in the diagnosis and follow-up studies of Wilson's disease. [German],,adolescent;article;biopsy;chemical analysis;follow up;human;liver/an [Drug Analysis];long term care;neutron;pathology;prognosis;technique;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper/an [Drug Analysis];diagnostic agent;penicillamine/dt [Drug Therapy],"Henke, G.;Mollmann, H.;Althoff, W.",1971,1 Mar,,0,0,
3023,Wilson's disease. 2 cases with damage to liver cells and renal tubules treated with penicillamine. [Danish],,adolescent;article;biosynthesis;female;human;kidney tubule;liver;male;metabolism;pathology;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy];serum albumin,"Gregersen, G.;Frederiksen, G.",1971,23 Jul,,0,0,
3024,Penicillin allergy--penicillamine allergy. A successful desensitization of a penicillamine allergy with penicillin G in mobus Wilson. [German],,adolescent;article;chemically induced disorder;desensitization;drug hypersensitivity/dt [Drug Therapy];genetics;human;intradermal drug administration;male;rash;skin test;time;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/ad [Drug Administration];penicillin derivative/ae [Adverse Drug Reaction];penicillin G/dt [Drug Therapy],"Metz, G.;Pevny, I.;Metz, J.",1970,17 Jul,,0,0,
3025,Therapy of neurologic manifestations of Wilson's disease using penicillamine. [Czech],,adolescent;adult;article;female;human;male;neurologic disease;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Hartl, J.;Hauftova, D.",1970,Mar,,0,0,
3026,Studies of the hepatolenticular degeneration and results of its continuous therapy. [German],,adolescent;adult;article;blood;chemical phenomena;chronic disease;cytochemistry;diet therapy;enzymology;female;hepatitis/di [Diagnosis];human;liver/an [Drug Analysis];liver cirrhosis/di [Diagnosis];liver function test;male;pathology;scintiscanning;stimulation;urine;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];acid phosphatase/an [Drug Analysis];alkaline phosphatase/an [Drug Analysis];cyanocobalamin/dt [Drug Therapy];iron;penicillamine/dt [Drug Therapy];plasma protein/an [Drug Analysis];potassium/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];sulfide/dt [Drug Therapy];triacylglycerol lipase/an [Drug Analysis],"Brailski, C.;Kolarski, V.;Krastev, I.",1970,,,0,0,
3027,Laboratory changes and complications during long-term therapy of Wilson's disease using D-penicillamine. [Czech],,article;blood;human;metabolism;time;urine;Wilson disease/dt [Drug Therapy];ceruloplasmin/an [Drug Analysis];copper;iron;penicillamine/dt [Drug Therapy];uric acid,"Hauftova, D.;Slavicek, J.;Hartl, J.;Seidlova, V.;Komenda, S.",1970,Apr,,0,0,
3028,Clinical aspects of hepato-lenticular degeneration. [Italian],,article;human;liver;metabolism;motor dysfunction/et [Etiology];pathophysiology;urine;Wilson disease;copper;penicillamine,"Fazio, C.;Agnoli, A.;Casacchia, M.",1970,1970,,0,0,
3029,Penicillamine in the treatment of Wilson's disease. Clinical picture. [Czech],,adolescent;adult;article;child;female;handwriting;human;male;neurologic disease;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Hauftova, D.;Hartl, J.;Seidlova, V.;Ruzickova, R.;Kubena, K.;Slavicek, J.",1970,Apr,,0,0,
3030,Therapy of Wilson's disease. [German],,article;human;metabolism;Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;penicillamine/dt [Drug Therapy],"Baumgartner, G.",1969,7 Mar,,0,0,
3031,Late cutaneous lesions due to penicillamine in a patient with Wilson's disease. [French],,adolescent;article;chemically induced disorder;drug eruption/et [Etiology];human;male;pathology;rash;skin;skin disease;time;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Christeler, A.;Delacretaz, J.",1969,,,0,0,
3032,On methods of copper determination in body fluids in disorders of copper metabolism. [German],,article;clinical chemistry;human;photometry;technique;urine;Wilson disease;copper;penicillamine/dt [Drug Therapy];quinoline derivative;thiocarbamic acid derivative,"Kamm, G.",1969,,,0,0,
3033,Iron and copper metabolism in hemochromatosis and Wilson's disease. Studies on relatives of patients. [German],,adolescent;adult;article;biopsy;blood;female;genetics;hemochromatosis;human;in vitro study;liver;metabolism;middle aged;pathology;scintiscanning;urine;Wilson disease;copper;diagnostic agent;iron;penicillamine,"Petera, V.;Lahn, V.;Virt, S.;Volenikova, L.;Kohout, J.",1969,15 May,,0,0,
3034,2 cases of Wilson's disease with hepatic precession in biliary lithiasis. [French],,adolescent;adult;article;cholelithiasis/co [Complication];female;human;jaundice/et [Etiology];Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Dupuy, R.;Vallin, J.;Fabiani, F.",1969,,,0,0,
3035,Pemphigus in a patient treated with penicillamine for Wilson's disease. [French],,adolescent;article;chemically induced disorder;human;male;pemphigus/co [Complication];Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Degos, R.;Touraine, R.;Belaich, S.;Revuz, J.",1969,,,0,0,
3036,"Clinical, therapeutic and isotopic study of familial Wilson's disease: desensitization to penicillamine D. [French]",,adult;article;child;desensitization;drug eruption/et [Etiology];female;genetics;human;isotope dilution assay;male;preschool child;Wilson disease/dt [Drug Therapy];copper;diagnostic agent;penicillamine/ae [Adverse Drug Reaction],"Mirouze, J.;Jaffiol, C.;Mary, P.",1969,,,0,0,
3037,Hepatolenticular degeneration. Wilson's disease. [Danish],,age;blood;human;liver cirrhosis/co [Complication];metabolism;pathology;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;copper;diagnostic agent;penicillamine/dt [Drug Therapy];radioisotope,"Hansen, H. J.;Andersen, O. S.",1969,31 Jul,,0,0,
3038,"Hepatolenticular degeneration, Wilson's disease. A characteristics case with remission under penicillamine therapy. [Danish]",,adolescent;adult;article;female;human;liver cirrhosis/dt [Drug Therapy];time;tremor/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Hansen, J.;Andersen, O. S.",1969,31 Jul,,0,0,
3039,Penicillamine treatment of Wilson's disease. [Swedish],,article;child;female;genetics;human;liver;metabolism;pathology;urine;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Falkmer, S.;Samuelson, G.;Sjolin, S.",1969,14 May,,0,0,
3040,Current problems of Wilson's disease (hepatolenticular degeneration). [Hungarian],,adolescent;article;blood;genetics;human;male;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Julesz, J.;Bodor, F.;Szarvas, F.",1969,7 Dec,,0,0,
3041,Motometric studies in the diagnosis and observation of the course of Wilson's disease. [German],,article;child;human;male;motor performance;neurologic examination;pathophysiology;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Jochmus, I.;Krienitz, B.;Rey, U.",1969,Jul,,0,0,
3042,Wilson's disease: hepatocerebral degeneration. 2. Clinical findings and therapy. [German],,adult;article;female;human;male;prognosis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Kunath, B.;Biesold, D.",1969,19 Jun,,0,0,
3043,Physiopathological and therapeutic considerations on a case of Wilson's disease. [Italian],,article;child;female;human;metabolism;pathophysiology;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Di Simone, A.;Manacorda, A.",1968,1968,,0,0,
3044,Anatomo-clinical study of a case of Wilson's disease treated with chelating agents for 5 years. [French],,acute kidney failure;adult;article;basal ganglion;chemically induced disorder;female;globus pallidus;human;liver;liver cirrhosis;pathology;splenectomy;splenomegaly/et [Etiology];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Boudin, G.;Pepin, B.;Milhaud, M.;Jerome, H.;Pacilly, A.",1968,Jan,,0,0,
3045,"Changes in the content of several microelements (copper, iron, zinc, manganese and molybdenum) in the blood and urine in hepato-cerebral dystrophy. [Russian]",,adolescent;adult;article;blood;female;human;male;metabolism;urine;Wilson disease/dt [Drug Therapy];copper;iron;manganese;molybdenum;trace element;zinc,"Loiko, E. A.",1968,,,0,0,
3046,Wilson's disease (hepatolenticular degeneration). [Spanish],,adolescent;adult;article;blood;female;genetics;human;urine;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Ferrer, S.;Grismali, J.;Vergara, F.;Madrid, R.;Colombo, M.",1968,Dec,,0,0,
3047,Wilson's disease treated by penicillamine: favorable effect. [French],,adolescent;adult;article;female;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Petit, H.",1968,Dec,,0,0,
3048,Treatment of Wilson's disease. [French],,article;drug potentiation;human;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Pepin, B.;Barraine, R.",1968,Feb,,0,0,
3049,Functional disorders of the renal tubules in Wilson's disease. [Dutch],,article;child;human;kidney disease/co [Complication];kidney tubule;male;metabolism;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Holl, H.;Troelstra, J. A.",1968,30 Nov,,0,0,
3050,"Glossitis, stomatitis and onychopathy caused by penicillinamine. [French]",,article;chemically induced disorder;child;drug effect;drug hypersensitivity;female;glossitis;human;nail;stomatitis;Wilson disease/dt [Drug Therapy];penicillamine/ae [Adverse Drug Reaction],"Thivolet, J.;Perrot, H.;Francois, R.",1968,,,0,0,
3051,Presymptomatic and hepatic forms of Wilson's disease in childhood. Long-term therapy with D-penicillamine. [German],,article;blood;child;classification;genetics;human;male;preschool child;Wilson disease/dt [Drug Therapy];ceruloplasmin;penicillamine/dt [Drug Therapy],"Kittoe, K.;Colombo, J. P.",1968,10 Dec,,0,0,
3052,Effects of the combined administration of glutathione and D-penicillamine on the urinary copper excretion in Wilson's disease. [Japanese],,adolescent;article;blood;drug antagonism;drug potentiation;female;genetics;human;pH;urine;Wilson disease/dt [Drug Therapy];buffer;ceruloplasmin;copper;glutathione/ad [Drug Administration];oxidoreductase;penicillamine/ad [Drug Administration],"Atsuba, Y.;Nakahachi, T.;Terai, T.;Kozakai, T.",1968,Feb,,0,0,
3053,"New views on the etiology, diagnosis and therapy of Wilson's disease. [German]",,blood;diet therapy;differential diagnosis;human;review;urine;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];Wilson disease/th [Therapy];ceruloplasmin/an [Drug Analysis];copper;oxidoreductase;penicillamine/dt [Drug Therapy],"Linke, A.",1967,15 Dec,,0,0,
3054,Long-term treatment of Wilson's disease with D-penicillamine. Report on 20 cases. [German],,adolescent;adult;article;genetics;human;inborn error of metabolism;metabolism;middle aged;nutritional deficiency;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin;copper/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];sulfate/dt [Drug Therapy],"Lange, J.",1967,15 Sep,,0,0,
3055,On the course and therapy of a juvenile Wilson's disease case. [German],,adolescent;article;diet therapy;female;human;neurologic disease;psychosis;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Wallauer, P.;Harbauer, H.",1967,30 Jun,,0,0,
3056,Current indications for penicillamine. [French],,human;liver disease/dt [Drug Therapy];review;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];penicillamine/to [Drug Toxicity],"Pommey, B.",1967,1967,,0,0,
3057,Biochemical bases and therapeutic possibilities of K. Wilson's hepatolenticular degeneration. [Spanish],,human;pathology;review;Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];chelating agent/dt [Drug Therapy];copper/pd [Pharmacology];cortisone/dt [Drug Therapy];edetic acid/dt [Drug Therapy];estrogen/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Grau-Veciana, J. M.;Barraquer-Bordas, L.",1967,1967,,0,0,
3058,Kidney diseases caused by drugs. [German],,acute kidney failure;adult;anemia/dt [Drug Therapy];article;chemically induced disorder;chronic kidney failure;drug therapy/ae [Adverse Drug Reaction];Fanconi renotubular syndrome;female;glomerulonephritis;human;kidney disease;male;middle aged;nephrotic syndrome;potassium deficiency;retroperitoneal fibrosis;rheumatoid arthritis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];dextran/ae [Adverse Drug Reaction];hydralazine/ae [Adverse Drug Reaction];methysergide/ae [Adverse Drug Reaction];penicillamine/ae [Adverse Drug Reaction];phenacetin/ae [Adverse Drug Reaction];sulfonamide/ae [Adverse Drug Reaction];tetracycline/ae [Adverse Drug Reaction],"Thiele, K. G.;Muehrcke, R. C.;Berning, H.",1967,8 Sep,,0,0,
3059,Contribution to the clarification of the pathogenesis of osteopathies in Wilson's disease. (Hepatolenticular degeneration). [Czech],,adolescent;article;blood;case report;human;male;metabolism;osteopathic medicine;urine;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];calcium;penicillamine/dt [Drug Therapy];phosphorus;strontium,"Vokrouhlicka Rosslerov, I.;Vodickova, L.;Neruda, O.",1967,Oct,,0,0,
3060,Mental disorders in Wilson's disease and the effect on them of penicillamine therapy. [Czech],,adolescent;adult;article;child;female;human;male;mental disease/dt [Drug Therapy];mental disease/et [Etiology];Wilson disease/co [Complication];penicillamine/dt [Drug Therapy],"Ruzickova, R.;Hauftova, D.",1967,Aug,,0,0,
3061,Hepatic changes in the neurological form of Wilson's disease. [Czech],,adolescent;adult;article;female;human;liver cirrhosis/et [Etiology];male;splenomegaly/et [Etiology];Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Hauftova, D.;Hartl, J.;Slavicek, J.;Valach, V.;Fialova, J.;Pojerova, M.",1967,Nov,,0,0,
3062,Urine copper determination in Wilson's disease during therapy. [German],,adult;article;blood;blood cell count;child;human;male;neurologic disease;urine;Wilson disease/dt [Drug Therapy];copper;penicillamine/dt [Drug Therapy],"Schnack, H.",1967,,,0,0,
3063,Experiences with long-term therapy of Wilson's disease. [German],,adolescent;article;blood;diet therapy;female;human;time;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;penicillamine/dt [Drug Therapy],"Schindler, H.",1967,,,0,0,
3064,Wilson's disease. Introduction to current problems (early diagnosis and therapy). [German],,adolescent;adult;agranulocytosis;article;blood;chemically induced disorder;child;female;human;liver/an [Drug Analysis];male;neurologic disease;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;copper/an [Drug Analysis];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy],"Wewalka, F.",1967,,,0,0,
3065,Wilson's disease (hepatolenticular degeneration). [German],,adolescent;adult;biopsy;brain;child;human;liver cirrhosis;metabolism;mortality;pathology;pathophysiology;prognosis;review;Wilson disease/dt [Drug Therapy];ceruloplasmin/ad [Drug Administration];copper;dimercaprol/dt [Drug Therapy];edetic acid/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Bickel, H.",1966,Jan,,0,0,
3066,"Clinical, bioptic, biochemical and therapeutic study of a case of hepatolenticular degeneration of K. Wilson with pseudotumoral onset. [French]",,article;biopsy;blood;brain angiography;case report;child;eye disease;female;human;immunoelectrophoresis;intracranial pressure;neurologic disease;pathology;protein electrophoresis;Wilson disease/co [Complication];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin;penicillamine/dt [Drug Therapy],"Barraquer-Bordas, L.;Tolosa, E.;Grau-Veciana, J. M.;Salisachs-Rowe, P.",1966,,,0,0,
3067,10 years of penicillamine. [German],,chemically induced disorder;cystinuria/dt [Drug Therapy];drug eruption;human;lead poisoning/dt [Drug Therapy];leukopenia;male;mercurialism/dt [Drug Therapy];middle aged;nephrotic syndrome;review;thrombocytopenia;vitamin deficiency;Wilson disease/dt [Drug Therapy];gold/to [Drug Toxicity];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Werner, T.;Weinmann, H. M.",1966,18 Nov,,0,0,
3068,Therapeutic considerations on Wilson's disease. [Italian],,adult;article;human;male;mental disease/et [Etiology];motor dysfunction/et [Etiology];neurologic disease;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];dimercaprol/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Tavolato, B.;De Zanche, L.",1966,,,0,0,
3069,Penicillamine. [French],,adolescent;adult;article;human;lead poisoning/dt [Drug Therapy];male;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Pepin, B.;Barraine, R.",1966,15 Oct,,0,0,
3070,Effect of penicillamine on human collagen and its possible application to treatment of scleroderma,,adult;aged;article;cystinuria/dt [Drug Therapy];female;human;male;metabolism;middle aged;rheumatoid arthritis/dt [Drug Therapy];skin;systemic sclerosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];collagen;penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology],"Harris Jr, E. D.;Sjoerdsma, A.",1966,5 Nov,,0,0,
3071,Nucleic acids in hepato-cerebral dystrophy. [Russian],,adolescent;adult;article;blood;female;human;liver/an [Drug Analysis];male;mathematics;middle aged;Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];DNA/an [Drug Analysis];glucose/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phospholipid;phosphorus;RNA/an [Drug Analysis];thiol derivative/dt [Drug Therapy];vitamin B complex/dt [Drug Therapy],"Korshunova, T. S.",1966,,,0,0,
3072,On the early diagnosis of Wilson's disease. [German],,article;case report;child;female;human;preschool child;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Gebert, P.;Biesold, D.",1965,Oct,,0,0,
3073,Splenomegalic cirrhosis in a 26-year old man: hepatolenticular degeneration with only splanchnic manifestations. [French],,adult;article;case report;human;male;splenomegaly/et [Etiology];Wilson disease/di [Diagnosis];penicillamine/dt [Drug Therapy],"Julien, C.;Caroli, J.;Valla, A.;Pousset, J. L.",1965,Sep,,0,0,
3074,Therapeutic effects of penicillamine on Wilson's disease. [Japanese],,adult;article;case report;child;human;in vitro study;male;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Takagi, H.;Yoshida, K.;Okamura, S.;Maehashi, M.",1965,Oct,,0,0,
3075,Hepatocerebral degeneration (Wilson's disease). 2. Therapy. [German],,adult;article;female;human;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy],"Werner, T.;Weinmann, H.",1965,12 Nov,,0,0,
3076,Hepatolenticular degeneration. The clinical course in two siblings during penicillamine therapy. [Danish],"A characteristic case of Wilson's disease in a girl aged 17 years is presented. The symptoms were exclusively neurological and extremely severe but underwent considerable remission during penicillamine therapy. A brother aged 10 years who had no symptoms was demonstrated biochemically to have Wilson's disease with slight involvement of the liver. He has been submitted to penicillamine therapy, provisionally for one year. Wilson's disease should be borne in mind as a possibility in the differential diagnosis when hepatic or neurological or psychiatric symptoms occur in children or young people.",case report;central nervous system;liver;school child;therapy;Wilson disease;penicillamine,"Hojer-Pedersen, E.",1979,,,0,0,
3077,The therapeutic use of d-penicillamine in the light of most recent pharmacokinetic and clinical observations. [Polish],,cystinuria;drug therapy;liver;pharmacokinetics;therapy;Wilson disease;chelating agent;penicillamine;penicillin G,"Sarosiek, J.;Rudy, J.",1979,,,0,0,
3078,Wilson's disease. A misdiagnosed case with purely neurological manifestations. [Danish],"A case of Wilson' disease, previously diagnosed as hysteria, is presented. There was convincing effect of dimethylcysteine (Penicillamin) and low copper diet on the ataxia. It is suggested that all patients with unexplained ataxia, liver disorders or large numbers of spontaneous abortions should be screened by examination of the eyes for Kayser-Fleischer rings, and estimations of serum coeruloplasmin (low) and urinary copper (high).",case report;central nervous system;liver;Wilson disease;ceruloplasmin;copper;penicillamine,"Klee, J. G.",1979,,,0,0,
3079,Nephrotoc syndrome induced by D-penicillamine therapy,"The paper presents a female patient in whom penicillamine therapy for aggressive hepatitis triggered the development of nephrotic syndrome. Histological findings revealed membranous glomerulonephritis. After the withdrawal of penicillamine therapy, the laboratory results returned to normal. The authors concluded that penicillamine should only be administered in conditions in which other means of therapy prove inefficient (i.e. Wilson's disease, cystinuria associated with calculi).",adverse drug reaction;case report;diagnosis;hepatitis;histology;kidney;liver;nephrotic syndrome;oral drug administration;penicillamine,"Jezersek, P.;Ferluga, D.",1979,,,0,0,
3080,Wilson's disease. [Dutch],,adverse drug reaction;blood and hemopoietic system;drug therapy;familial disease;kidney;leukopenia;liver;liver cirrhosis;nephrotoxicity;oral drug administration;pregnancy;skin toxicity;therapy;Wilson disease;penicillamine;pyridoxine,"Bollen, J.;Seurynck, D.;Proesmans, W.",1978,,,0,0,
3081,Monocytic lymphadenitis coli with morbilliformous exanthema as a side effect of the penicillamine therapy of infantile Wilson disease. [German],,adverse drug reaction;case report;drug therapy;liver;lymphadenitis;lymphatic system;monocyte;oral drug administration;rash;school child;therapy;Wilson disease;penicillamine,"Rabenalt, P.",1978,,,0,0,
3082,Wilson's disease in a Black patient. [Afrikaans],,case report;diagnosis;ethnic or racial aspects;liver;therapy;Wilson disease;penicillamine,"Van Der Merwe, C. F.;Padayatchi, P.",1978,,,0,0,
3083,Effect of D penicillamine on the hepatic gliopathy in tissue culture. [Polish],"Studies were carried out to determine the effect of d-penicillamine on the morphologic, histochemical and electron microscopic picture of gliopathy developing in glial tissue cultured in medium containing either the serum taken from patients suffering from hepato-lenticular degeneration and hepatic coma or in medium containing normal serum to which exogenous copper and ammonium salts had been added. It was found that penicillamine distinctly reduces the cytotoxic action of serum obtained from patients affected with hepato-lenticular degeneration. The effect was less evident when the serum from patients suffering from hepatic coma and serum containing exogenous copper salts were used. There was no abatement of cytotoxic effect of ammonia. The above observations led to the assumption that the protective effect of penicillamine comes into evidence only in the cases in which copper is the sole or concomitant pathogenic factor. The partial mitigating effect of penicillamine noted in cultures with serum containing exogenous copper and in cultures with serum from the patients affected with hepatic coma is attributed in the former case to an excess of copper salts in relation to penicillamine, and in the latter to a common action of copper and ammonia, pathogenic factors of equal rank.",cell culture;culture medium;cytology;electron microscopy;glia cell;hepatic coma;histochemistry;in vitro study;liver cell;major clinical study;serum;tissue culture;Wilson disease;ammonia;copper;penicillamine,"Mossakowski, M. J.;Krasnicka, Z.;Gajkowska, B.",1977,,,0,0,
3084,Pick's disease and zinc metabolism. [French],"A number of findings support the hypothesis of an abnormality of zinc metabolism in Pick's disease. This disease seems to be related to enhanced concentrations of zinc in tissues (brain and red cells) along with an increase of the urinary excretion of this metal, possibly correlated with a primary or secondary disturbance of zinc transport by blood proteins. The positive correlation of the level of serum zinc with the quantity of alpha<inf>1</inf> globulins, as well as the increase of the latter in Pick's disease, suggest a physiopathology which could be closer to hemochromatosis than to hepatolenticular degeneration. Confirmation of this hypothesis would require the replication of our own results by other research teams, more specific studies of the modalities of zinc transport by plasma proteins, and global evaluations of this metal metabolism in Pick's disease.",Alzheimer disease;central nervous system;dementia;hippocampus;major clinical study;pick disease (arnold);disulfiram;edetate calcium;iron;plasma protein;zinc,"Constantinidis, J.;Richard, J.;Tissor, R.",1977,,,0,0,
3085,Changes of bioelectrical brain activity in hepatocerebral dystrophy (Wilson Konovalov's disease) (Russian). [Russian],,brain;central nervous system;electricity;Wilson disease;copper;penicillamine,"Petushkov Ye, P.;Vakharlovsky, V. G.",1977,,,0,0,
3086,Children of mothers with hepatolenticular degenerescence (Rumanian). [Romanian],,child;major clinical study;Wilson disease;penicillamine,"Christodorescu, D.;Magureanu, S.",1977,,,0,0,
3087,The pregnant woman with Wilson's disease,,fetus;pregnancy;serum;therapy;Wilson disease;ceruloplasmin;copper;penicillamine,"Albukerk, J. N.;Scheinberg, I. H.;Sternlieb, I.",1976,,,0,0,
3088,Wilson's disease. 3 cases treated with penicillamine. [Spanish],,clinical study;drug therapy;intramuscular drug administration;major clinical study;oral drug administration;therapy;Wilson disease;penicillamine,"Balcells, A.;Cabrer, B.;Cano, J. F.",1976,,,0,0,
3089,Mannosidosis and maternal penicillamine therapy,,adverse drug reaction;drug therapy;embryotoxicity;fetus;lysosome;mannosidosis;oral drug administration;pregnancy;therapy;Wilson disease;cobalt nitrate;ferrous sulfate;magnesium chloride;penicillamine;pyridoxine;unclassified drug;zinc sulfate,"Arbisser, A. I.;Scott Jr, C. I.;Howell, R. R.",1976,,,0,0,
3090,Goodpasture syndrome and D penicillamine,"It has recently been suggested that the Goodpasture syndrome may be caused by D penicillamine treatment. A patient (man of 51) is reported in whom the clinical picture of this syndrome occurred during treatment with this drug. Peritoneal dialysis was necessary and renal biopsy undertaken. Light microscopy showed several glomeruli that were totally sclerosed and 6 that had focal proliferative changes with prominent epithelial crescent formation. Immunofluorescence showed no deposits of IgG or complement components. A thin (one micron) section did not indicate the presence of immune complex deposits, and electron microscopy was therefore not done. Clinical features closely resembling those of this patient have recently been described in patients with Wilson disease, which was treated with D penicillamine. In these cases the features were ascribed to Goodpasture syndrome, and D penicillamine was incriminated as the causative agent. However, linear deposition of immunoglobulin on the glomerular basement membrane was not shown in any of these cases. This is a feature that is characteristic of Goodpasture syndrome, and its absence should preclude the use of this diagnostic term. For this reason it might be better to describe the illness as 'lung purpura and nephritis'. Nevertheless, the circumstantial evidence implicates D penicillamine in the clinical syndrome described and it is felt that this case report lends credence to the association reported by previous authors.",adverse drug reaction;clinical study;glomerulonephritis;Goodpasture syndrome;kidney biopsy;lung hemorrhage;major clinical study;oral drug administration;azathioprine;penicillamine;prednisolone,"Gibson, T.;Burry, H. C.;Ogg, C.",1976,,,0,0,
3091,Treatment of Wilson's disease,,chelation;drug binding;drug therapy;methodology;oral drug administration;therapy;Wilson disease;copper;penicillamine;trientine,"Bucur, I.;Hasselgren, K. H.",1975,,,0,0,
3092,Cuprenil 'Polfa' (d penicillamine) in treatment of hepatolenticular degeneration (Polish). [Polish],,drug therapy;major clinical study;therapy;Wilson disease;penicillamine,"Hasik, J.;Kozal, H.",1975,,,0,0,
3093,Combined use of S adenosylmethionine and penicillamine in Wilson's disease. [Italian],,drug mixture;drug therapy;liver function test;major clinical study;therapy;Wilson disease;penicillamine;s adenosylmethionine,"Gasbarrini, G.;Miglio, F.;Corazza, G. R.;Stefanini, G. F.",1975,,,0,0,
3094,Complex medicamentous and surgical treatment of hepatolenticular degeneration (Russian). [Russian],"Treatment of 2 patients with a tremulous form of hepatolenticular degeneration comprised stereotaxic implantation of electrodes into the brain, and a course of therapeutic electric stimulation covering some points of the mesencephalic region without their destruction. Following elimination of bilateral hyperkinesia, low doses of D penicillinamine were administered. The effect of this treatment was maintained for 3 postoperative yr. Conservative therapy had proved of no avail. It is suggested that with unchanged genotype, electric stimulation tends to abolish the 'persistent pathologic status' and to favorably alter the phenotype of the patients. It is advisable to examine relatives of the patients for early recognition of cases of the presymptomatic form, and of carriers of the hepatolenticular degeneration genes, which is of importance in medicogenetic consultations.",diagnosis;major clinical study;mesencephalon;phenotype;stereotaxic surgery;theoretical study;therapy;Wilson disease,"Bondarchuk, A. N.;Borodkin Yu, S.;Vakharlovsky, V. G.",1975,,,0,0,
3095,Epilepsy and hepatolenticular degeneration (Serbocroatian). [Serbian],"Manifestation of epilepsy and paroxysmal EEG changes in Wilson's disease are rare. In one of the authors' patients who died in status epilepticus characteristic patho anatomic changes in the liver and brain were found. One other patient frequently had petit mal attacks which could be completely suppressed with D penicillamin. The authors describe two cases of hepatolenticular degeneration with specific changes in the EEG, but without epilepsy. This EEG change completely disappeared during treatment with D penicillamin. Epileptic crises in the beginning of the disease, without completely developed biochemical changes, may be a diagnostic problem. The most important problem is treatment and how to recognize disease as soon as possible. (Journal received: April 1977)",diagnosis;electroencephalography;epilepsy;major clinical study;petit mal;Wilson disease;penicillamine,"Ledic, P.;Sepcic, J.;Antoncic, N.;Sepic, D.",1975,,,0,0,
3096,The activity of aminotransferases in serum and cerebrospinal fluid in neurological diseases. [German],"The activities of the aminotransferases, GOT and GPT, were determined in the serum and cerebrospinal fluid of patients with Parkinson's disease, Huntington's chorea, Wilson's disease, amyotrophic lateral sclerosis (ALS), Friedreich's ataxia, phenylketonuria, and head injuries. In patients with Huntington's chorea the activity of SGOT was lower than in controls (P = 0.02), in Friedreich's ataxia LGPT activity was decreased (P<0.001); in patients suffering from ALS SGOT (P = 0.005), SGPT (P<0.001) and LGOT (P<0.001) activities were increased. Long term treatment of Parkinson's disease and Wilson's disease with L dopa resulted in an increase in SGOT, LGOT, and SGPT activity over approximately 2 mth, with subsequent normalization of these enzyme activities in spite of continued therapy. Guanidine treatment led to an increase in aminotransferase activities in patients with ALS. Penicillamine caused a decrease in SGOT and SGPT activities in Wilson's disease. These results illustrate the necessity of taking therapeutic measures into account in the interpretation of data on aminotransferase activities.",amyotrophic lateral sclerosis;cerebrospinal fluid;diagnosis;etiology;Friedreich ataxia;head injury;Huntington chorea;injury;liquid;Parkinson disease;phenylketonuria;serum;Wilson disease;amantadine;aminotransferase;guanidine;penicillamine,"Weiss, J.;Grundig, E.;Gerstenbrand, F.",1975,,,0,0,
3097,Etiology of the juvenile chronic hepatitis. [Spanish],,alpha 2 antitrypsin deficiency;child;chronic active hepatitis;cytology;diagnosis;etiology;histology;liver cirrhosis;major clinical study;methodology;virus hepatitis;Wilson disease;copper;hepatitis B antigen;penicillamine,"Villagrasa, M.;Guardia, J.;Martinez Vazquez, J. M.",1975,,,0,0,
3098,"Familial Wilson's disease: copper induced hemolysis, hypersplenism and hyperpigmentation as leading symptoms. [German]","Wilson's disease was diagnosed in a 16 yr old boy who presented with signs of hypersplenism due to liver cirrhosis, with marked hyperpigmentation of lower legs and neurologic disturbances. In view of progressive thrombocytopenia and leukocytopenia, splenectomy was performed during therapy with penicillamine later in the course, and the result was good. The patient's 12 yr old sister was found to have a hepatic form of Wilson's disease with typical biochemical findings. During the initial hospitalization, a severe spontaneous copper induced hemolysis was noted. Another sister probably has a presymptomatic form of the disease. The parents are healthy but heterozygote carriers with regard to biochemical findings. The importance is stressed of hypersplenism, hyperpigmentation of the legs and especially of acute hemolysis in infancy as pointers in the diagnosis of Wilson's disease. Further diagnostic and therapeutic aspects are discussed.",adverse drug reaction;drug therapy;hemolysis;hyperpigmentation;hypersplenism;leukopenia;major clinical study;oral drug administration;pruritus;therapy;thrombocytopenia;Wilson disease;penicillamine,"Steiner, P.;Frey, P.;Lupi, G. A.;Kistler, H. J.",1975,,,0,0,
3099,Drugs for rare diseases,,drug analysis;drug industry;drug research;methodology;Wilson disease;penicillamine,"Lyle, W. H.",1974,,,0,0,
3100,Stomatitis caused by D penicillamine. [French],"The authors recall the chemical structure of D penicillamine, its pharmacological properties and its main indications: Wilson's disease and rheumatoid polyarthritis. Treatment by D penicillamine may cause digestive, neurological, haematological and renal accidents and also cutaneo mucosal accidents the study of which is very interesting. Apart from accidents of early onset of the pruriginous erythema type which appear to be allergic in nature, these accidents occur late after large doses have been taken and their mechanism is different: lupus erythematosus syndrome, erosive and lichenoid stomatitis, haemorrhagic detachment of the skin at pressure points with formation of epidermal microcysts apparently connected with the lathyrogenic effect of the product, bullous eruptions clinically, histopathologically and immunologically identified with pemphigus. The authors describe the case of a 49 year old woman who had been treated for 17 months by D penicillamine for rheumatoid polyarthritis. A pruriginous erythema of the face and the extremities which appeared in the 5th week gradually showed less and less response to antihistamines. After 14 months, a painful, erosive and keratotic stomatitis appeared which kept pace with the treatment and ceased rapidly when D penicillamine was withdrawn. Clinically it appeared similar to an erosive lichen planus, but histopathologically it appeared very different and there was in the epithelium an adumbration of acantholysis. It might therefore be an atypical pemphigus and penicillamine appears to be the first drug known which is capable of inducing this disease.",adverse drug reaction;drug eruption;erythema;etiology;pemphigus vulgaris;rheumatoid arthritis;stomatitis;therapy;penicillamine,"Kuffer, R.;Noble, J. P.",1973,,,0,0,
3101,Familial aspects of Wilson's disease. [Polish],A 27 yr old man was admitted to hospital with very advanced manifestations of Wilson's disease. He died from hepatic coma and massive esophageal hemorrhage due to varices. The pedigree of the proband showed another case of oligosymptomatic Wilson's disease. Many months' treatment with penicillamine in this case resulted in alleviation of neurological symptoms and an improvement in certain biochemical parameters.,esophagus varices;hepatic coma;liver cirrhosis;major clinical study;Wilson disease;penicillamine,"Malolepszy, J.;Cieslinska, A.;Affelska, I.",1973,,,0,0,
3102,Haemorrhagic diathesis in Wilson's disease. Plasmatic or thrombocytic genesis?. [German],"A qualitative change in the thrombocytes was inferred from the finding in 2 patients of restricted platelet function in the cold stress test, deficient aggregation in the presence of low ADP concentrations, and morphologic anomalies in the electron microscope. Such change seems to belong to the primary picture of Wilson's disease, as it is known to occur in the asymptomatic form. However, a drug effect could not be entirely excluded, as both patients were treated with D penicillamine. A hemorrhagic diathesis develops if the liver is secondarily damaged by copper deposition and the hemostatic condition deteriorates further. Thus with the decline of liver dependent plasma coagulation factors, petechial (and thus thrombocytic) bleeding phenomena become paradoxically manifest.",bleeding tendency;etiology;plasma;thrombocyte;Wilson disease;penicillamine,"Sutor, A. H.;Ketelsen, U. P.",1973,,,0,0,
3103,"Penicillamine, its metabolism and therapeutic applications: a review","Penicillamine has proved to be an excellent therapeutic agent for the treatment of Wilson's disease and cystinuria. However, its use in other disease states such as rheumatoid arthritis still remain controversial. This controversy has arisen largely because of the greater incidence of drug-induced side effects in patients with rheumatoid arthritis. For the most part the etiology of these side effects is not known and therefore it remains imperative that patients receiving penicillamine should be carefully monitored for adverse reactions. The measurements of penicillamine and its metabolic products may be a useful adjunct to the laboratory parameters currently employed to assess the patient's response to this drug. The mechanism by which penicillamine exerts its beneficial effects in different disease states is not understood. What is apparent however, is that the thiol group of penicillamine plays a critical role in determining the actions of the drug. Hence it follows that the action of penicillamine in situ will depend upon factors such as the physical state of the drug, its disposition in the body, and the rate of its metabolism and excretion. Hopefully, when more is known about these parameters it will prove more feasible to speculate on the mechanisms whereby penicillamine exerts both its beneficial as well as its deleterious effects. Much more research will be required if this goal is to be realized in the near future.",cystinuria;drug metabolism;drug therapy;heavy metal poisoning;joint;liver;liver disease;pharmacokinetics;review;rheumatoid arthritis;scleroderma;therapy;Wilson disease;collagen;penicillamine,"Crawhall, J. C.;Lecavalier, D.;Ryan, P.",1979,,http://dx.doi.org/10.1002/bdd.2510010205,0,0,
3104,Elastosis perforans serpiginosa caused by penicillamine. [German],,adverse drug reaction;case report;elastosis perforans serpiginosa;histology;oral drug administration;therapy;Wilson disease;penicillamine,"Bardach, H.",1979,,,0,0,
3105,Copper excretion in patients with Wilson's disease under treatment with penicillamine. [Italian],,central nervous system;copper blood level;copper excretion;drug therapy;liver;major clinical study;oral drug administration;therapy;Wilson disease;penicillamine,"Indaco, A.;Pellegrino, L.;Campanella, G.",1979,,,0,0,
3106,The effect of penicillamine on the mental disorders associated with Wilson's disease. [German],In 5 patients with a hepatocerebral degeneration the effect of penicillamine on the psychopathological changes in this illness is examined. 900 to 1800 mg. per os of the drug are administered daily. No supplementary psychiatric therapy is applied. Physical findings are checked after 5 to 7 months of treatment. Evaluation is made under clinical psychopathometric and psychological test criteria. In 4 of the 5 patients the transition syndrome has worked through after 5 to 7 months. In the treatment section of HAWIE a substantial increase in values when compared to first examinations (between 14 and 27 IQ points) corresponds to the above results. Only in the case of one patient does the clinical picture improve with a 7 month delay. From reported disease courses it emerges that the psychopathological changes in hepatocerebral degeneration are based not on irreverisble damage (dementia) but on restorable diminution in function of the brain.,central nervous system;drug therapy;mental disease;therapy;Wilson disease;antidepressant agent;neuroleptic agent;penicillamine,"Hach, B.;Hartung, M. L.",1979,,,0,0,
3107,Treatment of inflammatory and metal storage diseases of the liver,"No specific drug therapy is indicated for chronic persistent hepatitis since the prognosis in this condition if uniformly favourable. Corticosteroids and immunosupressive agents have been used in chronic active hepatitis for 20 years and in most controlled studies corticosteroids have been shown to prolong life. It is usual to start prednisone at 20 or 40 mg daily and taper the dose as symptoms and biochemical abnormalities improve. Azathioprine alone is no more effective than placebo. However, it has a steroid-sparing effect and allows lesser doses of corticosteroids. It is advisable to discontinue therapy gradually only when patients have remained in biochemical and histological remission for at least 6 months. Further trials are needed for the use of transfer factor, interferon and immunostimulation with levamisole. Treatment of symptomatic pre-cirrhotic primary biliary cirrhosis with azathioprine has not proved beneficial. However, there was improvement in cases of pruritus. A preliminary report from Mayo Clinic suggests that copper chelation therapy with D-penicillamine may be effective, with a significant improvement in serum gamma globulin, bilirubin and IgM levels. Supportive treatment and correction of malabsorption, fluid retention, portal hypertension and hepatic decompensation is of paramount importance. Pruritus may be relieved with cholestyramine or androgens. Fat soluble vitamins are administered following a monthly program of vitamin A, 100 000 I.U., vitamin D 100 000 I.U. and vitamin K, 10 mg. No pharmacological agent has unequivocally proved beneficial in the treatment of alcoholic hepatitis. The use of corticosteroids has been both advocated and condemned on the basis of a number of controlled and uncontrolled clinical trials. There is considerable evidence that iron is a contributing factor in the pathogenesis of idiopathic haemocromatosis. Two controlled studies showed that venesection therapy is effective as it concerns survival, liver function, skin pigmentation and diabetes mellitus. Twice weekly phlebotomies are recommended, each of 500 ml and serum iron concentration should be maintained below 150 ug/100 ml and the serum ferritin level kept in the low normal range. Chelation therapy with deforroxamine is impractical but may be used when venesecton therapy is not feasible. The cornerstone of the therapy for Wilson's disease (hepatolenticular degeneration) is removal of the copper. The most effective copper chelating agent is D-penicillamine. Numerous studies have demonstrated that patients with this once fatal illness may expect functonal recovery of both hepatic and neurological abnormalities. The initial dose is 500 mg 3 times a day, increased to 3 to 4 g daily until adequate cupriuresis is attained. One-third of the patients develop side-effects including rashes, thrombocytopenia, leukopenia, arthralgia and lymphadenopathy. Complications of this therapy may be managed by temporary withdrawal followed by re-initiation with steroid coverage. (Mattar - Sao Paulo)","alcohol liver disease;biliary cirrhosis;chronic hepatitis;drug therapy;gallbladder;hemochromatosis;hemosiderosis;hepatitis;liver;short survey;therapy;Wilson disease;2,3 dihydroxybenzoic acid;alcohol;azathioprine;calcifediol;colestyramine;copper;corticosteroid;dimercaprol;ergocalciferol;levamisole;menadione;penicillamine;placebo;prednisolone;prednisone;retinol","Powell, L. W.;Tolman, K. G.",1979,,,0,0,
3108,Wilson's disease: Increased aluminum in liver,Interaction of trace metal metabolism was studied in a patient with Wilson's disease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.,case report;etiology;liver;neutron activation analysis;pathogenesis;preliminary communication;school child;Wilson disease;aluminum;calcium;copper;manganese;penicillamine,"Yasui, M.;Yoshimasu, F.;Yase, Y.;Uebayashi, Y.",1979,,,0,0,
3109,Zinc in pediatrics. [Italian],"The authors describe the fundamental aspects of zinc metabolism, the interaction of this metal with others bivalent cations, the zinc-vitamin A correlations and the metal-dependent enzymes. Zinc deficiencies encountered in pediatric practice, i.e., nutritional deficiency, acute zinc deficiency during total parenteral nutrition and inherited metabolic diseases such as acrodermatitis enteropathica and hyperzyncemia, are discussed. Furthermore, zinc deficiency in different conditions, as sickle-cell disease, rheumatoid arthritis, Wilson's disease, acute and chronic infections, renal and hepatic chronic disease, is also pointed out. Finally, the use of pharmacological doses of zinc as sulphate is reported.",acrodermatitis enteropathica;child health care;drug metabolism;etiology;oral drug administration;preschool child;review;school child;zinc;zinc sulfate,"Rufini, S.;Toppetti, L.",1979,,,0,0,
3110,D-penicillamine in various diseases in childhood. [German],,adverse drug reaction;chronic liver disease;digestive system;drug therapy;fever;gastrointestinal symptom;immunopathology;joint;liver;nephrotic syndrome;oral drug administration;preschool child;proteinuria;rash;rheumatoid arthritis;school child;therapy;thrombocytopenia;Wilson disease;collagen;penicillamine,"Weingaertner, L.",1979,,,0,0,
3111,Copper levels after oral zinc,,human cell;normal human;oral drug administration;preliminary communication;Wilson disease;zinc blood level;copper;zinc,"Abdulla, M.",1979,,,0,0,
3112,Penicillamine,"This very complete article reviews the relationship of penicillamine to rheumatic disease therapy. This review includes a historical outline from its initial isolation through its early use in Wilson's disease in cystinuria and more recently its use with rheumatoid vasculitis and rheumatoid arthritis. The chemistry, pharmacology and pharmacokinetics as they are presently understood, are discussed. In general, while a number of theories are discussed as to pharmacological action, no single explanation is clearly responsible for the observable result in rheumatoid arthritis. The therapeutic discussion covers the role in Wilson's disease, cystinuria and rheumatoid arthritis. In rheumatoid arthritis, the rationale for current dosage schedules is given, side effects and their relationship to dosage in HLA genetics are adequately covered. The conclusion is that penicillamine is an effective agent in the treatment of this disease.",adverse drug reaction;blood and hemopoietic system;cystinuria;digestive system;gastrointestinal symptom;leukopenia;pharmacokinetics;pharmacology;proteinuria;rash;review;rheumatoid arthritis;scleroderma;systemic lupus erythematosus;taste;thrombocytopenia;Wilson disease;antiinflammatory agent;azathioprine;gold;penicillamine;penicillin G,"Lyle, W. H.",1979,,,0,0,
3113,Oral zinc sulphate as long-term treatment in Wilson's disease (hepatolenticular degeneration),"Clinical amelioration, clearance of Kayser-Fleischer rings and rising of ceruloplasmin concentration are described in a patient with the classical findings of Wilson's disease. These changes occurred during a 14-year period in which he used oral zinc sulphate (three times daily 200 mg) as the only medication to influence copper metabolism. Before starting this long-term zinc sulphate therapy he had used D-penicillamine (three times daily 300 mg) for only 6 weeks. The antagonistic action of zinc sulphate on copper resorption with amelioration of the clinical condition has been described before this patient in 1961 by Schouwink. The patient had used at that time oral zinc sulphate for approximately 1.5 years. No changes in Kayser-Fleischer rings and ceruloplasmin levels were mentioned. Our findings suggest that oral zinc sulphate may not only prevent storage of copper in the tissues but may also contribute to the mobilization and excretion of deposits of copper.",case report;central nervous system;drug therapy;kayser fleischer ring;liver;oral drug administration;therapy;Wilson disease;ceruloplasmin;copper;penicillamine;zinc sulfate,"Hoogenraad, T. U.;Koevoet, R.;de Ruyter Korver, E. G. W. M.",1979,,,0,0,
3114,Penicillamine-induced myasthenia gravis,D-penicillamine has been established as an effective agent in the management of rheumatoid arthritis. It is also used to treat patients with Wilson's disease and cystinuria. Myasthenia gravis has been reported to occur in patients receiving penicillamine treatment for both rheumatoid arthritis and Wilson's disease. This report describes two patients who developed myasthenia gravis while receiving penicillamine for the treatment of rheumatoid arthritis.,adverse drug reaction;case report;muscle;myasthenia gravis;oral drug administration;rheumatoid arthritis;therapy;acetylsalicylic acid;fenoprofen;gold;neostigmine;penicillamine;prednisone;pyridostigmine,"Sundstrom, W. R.;Schuna, A. A.",1979,,http://dx.doi.org/10.1002/art.1780220214,0,0,
3115,Copper metabolism: Report of a case of Wilson's disease,"Hepatolenticular degeneration has been recognized since the latter part of the nineteenth century, but Wilson's description in 1912 gave it the name by which it usually is called. Characterized by a hereditary deficiency of copper in the serum, the condition often is fatal, although the prognosis has improved since the introduction of penicillamine. The disease may manifest itself in many ways, and among the characteristic signs is a rusty brown corneal ring, which Wilson did not describe. Signs pointing to involvement of the central nervous system are common, and intellectual deterioraton may be present.",central nervous system;clinical study;congenital disorder;drug metabolism;genetic disorder;liver;major clinical study;tremor;visual system;Wilson disease;ceruloplasmin;copper;dimercaprol;penicillamine,"Watson, D. R.",1979,,,0,0,
3116,"Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E<inf>1</inf>, E<inf>2</inf>, and I<inf>2</inf> and penicillamine","Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC<inf>50</inf> 3 x 10-<sup>6</sup> M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE<inf>2</inf>). The dose-response curve was not shifted by indomethacin, imidazole, or PGE<inf>2</inf> but was moved to the right by 2.8 x 10<sup>-11</sup> M PGE<inf>1</inf> and to the left by 2.8 x 10-<sup>7</sup> M PGE<inf>1</inf>. These effects of copper are similar to the effects of PGI<inf>2</inf> in the preparation. Copper moved the PGI<inf>2</inf> dose-response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE<inf>1</inf> synthesis, had PGE<inf>1</inf>-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.",animal experiment;artery perfusion;blood pressure;cardiovascular system;dose response;drug interaction;drug response;great blood vessel;mesentery blood flow;peripheral vascular system;rat;regional perfusion;superior mesenteric artery;Wilson disease;angiotensin;copper;imidazole;indometacin;noradrenalin;penicillamine;potassium;prostacyclin;prostaglandin;prostaglandin E1;prostaglandin E2,"Cunnane, S. C.;Zinner, H.;Horrobin, D. F.;Manku, M. S.;Morgan, R. O.;Karmali, R. A.;Ally, A. I.;Karmazyn, M.;Barnette, W. E.;Nicolaou, K. C.",1979,,,0,0,
3117,Problems in treatment of rheumatic disease in pregnancy. [German],"Most antirheumatic drugs are potentially dangerous for the fetus during pregnancy. Higher rates of abortion and birth defects have been reported after both aspirin and chloroquine treatment. Postnatally hyperbilirubinemia may occur when aspirin or indomethacin has been given during pregnancy and a temporary adrenal deficiency may occur after treatment with glucocorticosteroids. P-penicillamine may cause connective tissue defects. The author also warns against treatment with gold and cytostatic drugs during pregnancy and lactation. The article has no references. (Hanse, Copenhagen).",adverse drug reaction;congenital disorder;cystinuria;drug therapy;hyperbilirubinemia;kernicterus;lupus erythematosus;pregnancy;rheumatic disease;teratogenesis;therapy;Wilson disease;alclofenac;azapropazone;azathioprine;benorilate;chloroquine;clofezone;diclofenac;flufenamic acid;gold salt;ibuprofen;indometacin;mefenamic acid;naproxen;niflumic acid;oxyphenbutazone;penicillamine;phenylbutazone;salicylic acid;trimenon;unclassified drug,"Bischof, P.;Kaiser, H.",1978,,,0,0,
3118,Hepatic copper in primary biliary cirrhosis: biliary secretion and response to penicillamine treatment,,abstract report;bile;bile duct;clinical study;drug therapy;liver;oral drug administration;primary biliary cirrhosis;therapy;Wilson disease;bile acid;ceruloplasmin;cholesterol;copper;penicillamine;phospholipid,"Salaspuro, M.;Pikkarainen, P.;Sipponen, P.",1978,,,0,0,
3119,Diagnosis and treatment of hepatolenticular degeneration. [German],,article;diagnosis;drug therapy;liver;therapy;Wilson disease;penicillamine;potassium sulfide;unclassified drug,"Hach, B.",1978,,,0,0,
3120,Cirrhosis of the liver. [German],,adverse drug reaction;biliary cirrhosis;drug abuse;galactosemia;hemochromatosis;liver cirrhosis;portal hypertension;short survey;Wilson disease;albumin;alcohol;amiloride;arsenic;chlorpromazine;colchicine;colestyramine;cytostatic agent;ergocalciferol;etacrynic acid;felypressin;furosemide;hydrochlorothiazide;lactulose;levodopa;mannitol;menadione;neomycin;penicillamine;prednisone;retinol;triamterene,"Horak, W.",1978,,http://dx.doi.org/10.1002/pauz.19780070301,0,0,
3121,Toxic effects of copper on cultured rat lenses,"Lenses from 60-day-old rats were cultured for 24 hr at 35degreeC in Tyrode's medium containing copper sulfate at concentrations of 0, 10, 20, 50 and 100 muM. Lenses incubated with 0 or 10muM copper remained clear. Lenses incubated with 20, 50 or 100muM copper became cloudy, the cloudiness increasing with increasing copper concentration and being more intense in the equatorial than in the central region. Glucose utilization was inhibited, lens sodium and water contents were increased, and lens potassium was decreased with increasing copper concentration. At 10muM, the copper concentration at which opacification first became observable, glucose utilization was inhibited 20% and lens sodium content was increased threefold compared to control lenses. Copper (100 muM) inhibited the active transport of <sup>86</sup>Rb and increased its passive transport to a substantially greater degree than it inhibited the glucose utilization of cultured lenses. EDTA in the medium afforded substantial protection from copper toxicity; D-penicillamine (used to treat diseases involving copper toxicity) and histidine afforded partial protection. Noteworthy clinical implications of these studies are discussed.",animal experiment;cataract;dose response;drug efficacy;drug interaction;drug response;drug toxicity;glucose utilization;in vitro study;intoxication;lens;lens culture;organ culture;rat;visual system;Wilson disease;copper;edetic acid;penicillamine;potassium;rubidium 86;sodium,"Coulter, Iii J. B.;Oliver, S. S.;Whitener, C. M.",1978,,http://dx.doi.org/10.1016/0014-4835%2878%2990064-7,0,0,
3122,"Wilson's disease, presenting as chronic active hepatitis","17 patients (8 males and 9 females) with Wilson's disease (mean age 12 years) presented with clinical, biochemical, and morphological features similar to those of chronic active hepatitis. Neurological dysfunction was evident in only 3 patients (mean age, 18 years); Kayser-Fleischer rings were absent in 8 patients and the serum ceruloplasmin was normal in 3 patients with severe hepatic failure. Smooth muscle, mitochondrial antibodies, and HbsAg were negative in all patients. Cirrhosis was present on initial liver biopsy in 15 patients. Despite D-penicillamine therapy (1.0 to 3.0 g daily) 4 patients died within 3 weeks of diagnosis from fulminant hepatic failure associated with hemolysis. A further 5 patients died within 2 years as a result of hepatic failure (3 patients), variceal hemorrhage (1 patient), and a lupus-like syndrome (1 patient). A sustained improvement was observed in 8 patients who remain well (mean survival time, 7 years) with near normal liver function tests and inactive hepatic histology. Wilson's disease patients presenting as chronic active hepatitis frequently exhibit atypical features: Kayser-Fleischer rings and neurological dysfunction can be absent, and both serum ceruloplasmin and serum copper can be normal especially if there is severe hepatocellular necrosis. As a result, diagnosis of Wilson's disease may be delayed, and once cirrhosis is established this form of Wilson's disease can have a poor prognosis despite D-penicillamine therapy. It is essential, therefore, that the diagnosis of Wilson's disease be excluded in all patients with chronic active hepatitis and chronic parenchymal liver disease of unknown etiology so that an optimum treatment response to D-penicillamine can be achieved.",adolescent;chronic hepatitis;liver;liver biopsy;liver cirrhosis;liver failure;major clinical study;school child;Wilson disease;copper,"Scott, J.;Gollan, J. L.;Samourian, S.;Sherlock, S.",1978,,,0,0,
3123,Oral zinc in Wilson's disease,,clinical study;drug comparison;drug interaction;liver;loading test;major clinical study;oral drug administration;therapy;visual system;Wilson disease;copper;penicillamine;radioisotope;zinc sulfate,"Hoogenraad, T. U.;Van Den Hamer, C. J. A.;Koevoet, R.;De Ruyter Korver, E. G. W.",1978,,,0,0,
3124,Penicillamine in pregnancy,,editorial;fetus;pregnancy;prescription;teratogenesis;Wilson disease;penicillamine,"Lyle, W. H.",1978,,,0,0,
3125,Wilson's disease. Experience with long term d-penicillamine therapy,,abstract report;blood and hemopoietic system;ceruloplasmin blood level;clinical study;copper blood level;copper urine level;drug efficacy;drug therapy;histology;liver;liver function;long term exposure;major clinical study;therapy;Wilson disease;penicillamine,"Batey, R. G.;Kirk, A.;Sherlock, S.",1978,,,0,0,
3126,Minerals in normal and cirrhotic liver. [German],"Concentrations of iron, copper and zinc were measured in postmortem specimens of liver, muscle and brain tissue by atomic absorption spectrophotometry. Concentrations varied markedly in normal liver specimens from person to person, but not in the other organ specimens. Copper concentrations in specimens from cirrhotic livers were normal in most cases, however, at the upper limit of normal in about 20% of the cases evaluated. Concentrations of zinc and iron were lower than normal in cirrhotic livers. Mineral concentrations were higher by a factor of 10-20 in liver specimens of patients with hemochromatosis or M. Wilson than in normals. Iron overloading as a consequence of therapy (secondary hemochromatosis) and liver changes due to longtime artificially elevated plasma copper levels may imitate the adult form of the 'classic' mineral storage diseases mentioned. Thus 'athrocytotic' liver cirrhosis, being caused or accompanied by metal excess has to be considered as a polyetiological syndrome.",autopsy;brain;central nervous system;diagnosis;hemosiderosis;histology;liver;liver cirrhosis;muscle;Wilson disease;copper;iron;zinc,"Brandt, G.;Spitzer, F.",1978,,,0,0,
3127,D-penicillamine induced mucocutaneous lesions with features of pemphigus,"Penicillamine (beta<inf>1</inf>beta<inf>2</inf> dimethylcysteine) is the drug of choice in the therapeutic management of Wilson's disease and cystinuria and has been used in the treatment of some heavy-metal intoxications. Recent studies have shown that it is efficacious in patients with rheumatoid arthritis. Side effects include sensitivity reactions, nephrotoxicity, bone-marrow suppression, hypogeusia, skin lesions, and the formation of autoantibodies. Two cases are described with the features of pemphigus which were attributed to penicillamine therapy.",adverse drug reaction;case report;connective tissue disease;drug eruption;histology;immunofluorescence;mouth;mouth ulcer;oral drug administration;pemphigus vulgaris;skin toxicity;stomatitis;therapy;autoantibody;pemphigus antibody;penicillamine,"Hay, K. D.;Muller, H. K.;Reade, P. C.",1978,,http://dx.doi.org/10.1016/0030-4220%2878%2990524-8,0,0,
3128,Chronic hepatitis. [French],,chronic hepatitis;clinical study;diagnosis;drug therapy;etiology;hemosiderosis;hepatitis virus;immunity;liver;pathogenesis;review;survey;therapy;virus hepatitis;Wilson disease;alcohol;azathioprine;penicillamine;prednisone,"Dive, Ch",1978,,,0,0,
3129,Involvement of the exocrine pancreas in Wilson's disease?. [German],A normal exocrine pancreatic function was demonstrated by the secretin-pancreozymin-test in five patients with Wilson's disease either without (n = 2) or with cirrhosis of the liver but without portal hypertension (n = 3). In another patient with cirrhosis of the liver without portal hypertension the pancreas was normal at post mortem examination. In two patients with cirrhosis of the liver and portal hypertension bicarbonate (n = 1) and amylase secretion (n = 2) were diminished. The regression of portal hypertension under therapy with penicillamine in one of the latter cases was paralleled by the return to normal of exocrine pancreatic function. It is concluded that exocrine pancreatic insufficiency in Wilson's disease is dependent on the development and the progression of cirrhosis of the liver and not due to a primary manifestation of the disease itself.,central nervous system;diagnosis;etiology;liver;liver cirrhosis;pancreas;secretin test;Wilson disease;hormone;penicillamine,"Lankisch, P. G.;Kaboth, U.;Koop, H.",1978,,,0,0,
3130,Hematologic (cytopenic) manifestations of Wilson's disease (hepatolenticular degeneration),"The records of 54 consecutive patients with Wilson's disease seen at the Mayo Clinic from 1952 through early 1977 were reviewed to determine the frequency of hematologic abnormalities in their initial evaluation. Leukopenia and thrombocytopenia sometimes have been ascribed to treatment with D-penicillamine and its toxicity; however, we have found cytopenia to be a frequent finding in the presenting laboratory data of patients with Wilson's disease. Twenty-eight patients (52%) had thrombocytopenia and 16 of these patients (30% of the total) also had leukopenia. Severe, acute, intermittent hemolytic episodes were the initial and only presenting complaint of one patient. Six of the patients with significant cytopenias had splenectomy, and in all cases the peripheral blood counts returned to normal values. Long-term treatment with D-penicillamine improved the hepatic and neurologic dysfunction in most patients, however, the cytopenias remained unchanged except in three patients (treated 2, 5, and 10 years).",blood and hemopoietic system;etiology;leukopenia;liver;major clinical study;oral drug administration;thrombocytopenia;Wilson disease;penicillamine,"Hoagland, H. C.;Goldstein, N. P.",1978,,,0,0,
3131,"The pharmacology of 2,3-dimercaptosuccinic acid and its potential use in arsenic poisoning","Arsenic (As<inf>2</inf>O<inf>3</inf>)-poisoned rats were treated with either 2,3-dimercaptosuccinic acid (DMS) or dimercaptopropanol (BAL) at doses of 30 mg/kg/day. A control group received no treatment. The total quantity of arsenic excreted was not significantly different in response to 4 days of treatment with either DMS or BAL. In addition, there was no difference between the two drug treatment groups in the residual arsenic content of brain, liver, kidney and spleen after treatment. Both drugs reduced the arsenic content of each tissue to approximately 40% of that of untreated controls. Previous studies have shown that DMS is orally effective for the treatment of lead poisoning. The LD50 of DMS was determined to be in excess of 3 g/kg in rats and mice, approximately 30 times the LD50 of BAL. No gross, histopathological or biochemical evidence of toxicity was observed in mice, rats or dogs which received DMS 5 days per week for 6 months. DMS did not affect the excretion of zinc, iron, calcium or magnesium. Urinary copper excretion was significantly elevated in response to 30 mg/kg of DMS, suggesting that the drug might also be useful for the treatment of Wilson's disease.",animal experiment;drug comparison;drug feces level;drug intoxication;drug urine level;feces;intoxication;intraperitoneal drug administration;mineral excretion;oral drug administration;rat;arsenic;arsenic trioxide;dimercaprol;lead;succimer,"Graziano, J. H.;Cuccia, D.;Friedheim, E.",1978,,,0,0,
3132,Wilson's disease affecting only the liver. Evolution after a year of treatment with penicillamine. [Spanish],,abstract report;child;clinical study;diagnosis;drug therapy;liver;liver cirrhosis;major clinical study;school child;therapy;Wilson disease;bromsulfophthalein;penicillamine,"De Juan, F.;Ros Mar, L.;Loris, C.",1978,,,0,0,
3133,Electrophysiological study on Wilson's disease - changes of visual evoked potential and EEG by d-penicillamine treatment,"Electroencephalograms and visual evoked potentials were studied over a long period of time in four patients with Wilson's disease by D-Penicillamine treatment and findings were compared with the respective clinical course and changes in VEP obtained from the occipital region in each case. Three cases with abnormal EEGs showed no EEG improvement during or after treatment with D-Penicillamine and low copper diet. All four patients showed large VEP amplitude of late component at the beginning of treatment. The amplitude of N (late component) became smaller with associated disappearance of the K-F rings in two cases and in the other case with associated improvement of motor disturbance without change in the K-F rings and laboratory data. In one case showing the largest amplitude at the beginning of treatment, the amplitude of N became gradually smaller in association with slight improvement of motor disturbance and hyperactivity.",central nervous system;drug therapy;electroencephalography;etiology;evoked visual response;liver;school child;therapy;visual system;Wilson disease;penicillamine,"Yasui, M.",1978,,,0,0,
3134,Thrombohemolytic thrombocytopenic purpura during penicillamine therapy,"Penicillamine therapy was associated with the development of thrombohemolytic thrombocytopenic purpura (TTP) in a 23-year-old woman. The immunological and hematological toxicity of penicillamine, as well as the occurrence of TTP with parent penicillin compounds, indicates a probable etiological role of this drug.",adverse drug reaction;blood and hemopoietic system;case report;etiology;thrombocytopenia;thrombocytopenic purpura;Wilson disease;actest;corticotropin;duracton;penicillamine;unclassified drug,"Ahmed, F.;Sumalnop, V.;Spain, D. M.;Tobin, M. S.",1978,,http://dx.doi.org/10.1001/archinte.138.8.1292,0,0,
3135,Current situation in the prophylaxis of Wilson's disease. [French],,prevention;therapy;Wilson disease;ceruloplasmin;penicillamine,"Sternlieb, I.",1977,,,0,0,
3136,Atypical manifestations of Wilson's disease in children. [German],"Although Wilson's disease belongs to the metabolic diseases that have been known for the longest time, the diagnosis is frequently missed, because the clinical picture is very variable. In particular it is often unknown that the classic neurological syndrome of a pseudosclerosis with corneal ring and clinically silent cirrhosis of the liver is usually manifested in adolescents or young adults. On the contrary, in childhood Wilson's disease runs a purely abdominal course. This can be manifested as chronic hepatitis, cryptogenic cirrhosis of the liver, or its complications (ascites, necrotic attacks, gastrointestinal bleeding) or as a haemolytic crisis. Even the typical lowering of the copper and ceruloplasmin levels in the serum may be absent. In 3 cases of Wilson's disease diagnosed in the University Paediatric clinic in Heidelberg the possibilities of atypical manifestations are described with the intention, by means of earlier diagnosis and therapy, to help not only the patient who is already suffering symptomatically, but also to help their brothers and sisters presymptomatically. Thus long-term treatment with D-penicallamin not only often achieves unexpected improvements in the manifestly ill, but much more is able to spare the still asymptomatic patient the appearing of organ damage to the liver and central nervous system.",child;diagnosis;hepatic coma;major clinical study;therapy;Wilson disease;copper;penicillamine,"Feist, D.;Schmid-Rueter, E.;Wesch, H.",1977,,,0,0,
3137,Wilson's disease: a common liver disorder?,"In two sibships 7 of 24 siblings were homozygous for Wilson's disease. In family A, the largest kindred of this recessively inherited disease thus far reported, the proband presented with chronic active hepatitis, one sibling died of cirrhosis, a second had clinical evidence of chronic liver disease and two others had biochemical and histologic changes in liver biopsy specimens. In family B the proband had cirrhosis and portal hypertension and one sibling had biochemical and histologic evidence of liver disease. All six living patients had low serum concentrations of ceruloplasmin and copper and a high 24-hr urinary excretion of copper, which was greatly increased by administration of D-penicillamine. None showed neurologic abnormalities and only one had Kayser-Fleischer rings (detectable only by slit-lamp examination). Each patient had an erythrocyte sedimentation rate (ESR) of 8 mm/h or less. After 3 and 2 yr, respectively, of D-penicillamine therapy the conditions of the two probands had improved. Liver function became normal in three siblings, and no abnormalities developed in the remaining one. Thus, since Wilson's disease may present with chronic active hepatitis or cirrhosis with a normal ESR and without ocular or neurologic signs, it may be a more common cause of liver disease in young people than has been appreciated.",chronic active hepatitis;clinical study;drug therapy;histology;inborn error of metabolism;major clinical study;microscopy;oral drug administration;pedigree;therapy;Wilson disease;ceruloplasmin;copper;hydrochlorothiazide;penicillamine;prednisone;pyridoxine;triamterene,"Thompson, W. G.;Hyslop St, P. G.;Barr, R.;Sass Kortsak, A.",1977,,,0,0,
3138,Wilson's disease. [German],"Wilson's disease is the result of chronic copper intoxication which firstly affects the liver and, when this organ is saturated with copper, progresses to affect the central nervous system, cornea, kidneys and myocardium. The usual cause of this uncommon nutritional disorder is a congenital lack of the enzyme which catalyses the incorporation of copper into caeruloplasmin. The clinical picture is varied and includes hepatic, neurological, psychiatric, hematological and renal symptoms. D-penicillamin has recently improved the prognosis. (24 references).",Wilson disease;ceruloplasmin;copper;penicillamine,"Moerl, M.;Gabriel, L.",1977,,,0,0,
3139,Morbus Wilson - Progressive fatal course of the hepatic form with apoplexy and abscess of the brain. [German],"The onset with a hemolytic crisis, as often decribed in the literature, led to the diagnosis of Wilson's disease. Treatment was immediately started in the usual way with diet and d-penicillamin. But the disease had already caused serius liver damage and renal lesions, and the patient died fourteen weeks after diagnosis. Examinatiom of further family members disclosed a cousin with impaired liver and kidney function, also suffering from the hepatic form of homozygous Wilson's disease.",agranulocytosis;brain abscess;cerebrovascular accident;child;diagnosis;hemolytic crisis;liver cirrhosis;major clinical study;therapy;Wilson disease;ceruloplasmin;copper;penicillamine,"Werner, J. P.;Helwig, H.",1977,,,0,0,
3140,"Morbus Wilson - Pathogenesis, diagnosis, therapy and course. [German]","During childhood, Wilson's disease becomes manifest mostly in the hepatic form. In children every case of cirrhosis of the liver, hemolysis with high levels of conjugated bilirubin in the serum, and otherwise in explicable tremor make it imperative to exclude or confirm the existence of Wilson's disease. A false diagnosis often delays the start of therapy with d-penicillamine and low-copper diet. The prognosis, which was still fatal a few years ago, has improved considerably thanks to new therapeutic possibilities.",clinical study;diagnosis;drug therapy;major clinical study;pathogenesis;therapy;Wilson disease;copper;dimercaprol;penicillamine,"Werner, J. P.;Helwig, H.",1977,,,0,0,
3141,Wilson's disease in the adult. A copper retention study with <sup>64</sup>Cu,"3 cases of Wilson's disease occurring in adults are reported. Onset of Wilson's disease occurs between 4 and 40 yrs of age, but is relatively rare in adults. In a typically progressed stage the disease may easily be diagnosed from findings of Kayser-Fleischer's corneal ring in addition to the clinical features as neurologic manifestation and liver involvement, but many problems remain concerning abnormal copper metabolism in Wilson's disease. The retention of radioactive copper (<sup>64</sup>Cu) was measured with a whole body counter in 3 patients with Wilson's disease, 4 of their family members and 2 control subjects. The <sup>64</sup>Cu retained in the body showed a high value in the patients with Wilson's disease which may reflect a larger copper pool than in normal subjects. The applicability of retention measurement with <sup>64</sup>Cu as a screening test is discussed. Study of the body retention of <sup>64</sup>Cu may be useful as a screening test to differentiate the carrier from normal individuals in the family of Wilson's disease. In Wilson's disease, excretion of urinary copper and body retention of radiocopper increased. Urinary copper in Wilson's disease may be excreted via the copper pool, rather than directly after absorption through the intestine.",diagnosis;drug metabolism;major clinical study;Wilson disease;copper 64;penicillamine;radioisotope,"Yoshida, K.;Noguchi, S.;Suzuki, M.",1977,,,0,0,
3142,IgA deficiency during D penicillamine treatment,,adverse drug reaction;clinical study;drug therapy;erythema;immune deficiency;immunoglobulin A deficiency;immunoglobulin deficiency;therapy;thrombocytopenia;Wilson disease;immunoglobulin A;penicillamine;phenytoin,"Hjalmarson, O.;Hanson, L. A.;Nilsson, L. A.",1977,,,0,0,
3143,Neonatal abnormalities associated with D penicillamine treatment during pregnancy,,adverse drug reaction;autopsy;congenital malformation;fatality;fetus;growth retardation;inguinal hernia;peritonitis;placenta insufficiency;pregnancy;rheumatoid arthritis;skin toxicity;teratogenesis;teratology;therapy;Wilson disease;penicillamine,"Solomon, L.;Abrams, G.;Dinner, M.;Berman, L.",1977,,,0,0,
3144,The effect of certain chelating compounds on the urinary excretion of copper by the rat: observations on their clinical significance,"A screening procedure is described to assess rapidly the clinical potential of chelating agents for the treatment of Wilson's disease. Rats were used as the test animal; they were kept in metabolic cages and the urine was collected in copper-free containers. The compounds investigated were given by mouth as a standard dose of 100 mg. Copper was determined by atomic absorption spectrophotometry. Basal urine copper excretion was 65.1 +/- SE 2.93 nmol/24 h (4.1 mug +/- 0.185). After penicillamine this rose to 367.1 nmol and after trien to 305.9 nmol. Certain compounds caused a reduction in the amount of copper excreted in the urine, probably by forming insoluble chelates with the metal, hence rendering it unavailable for excretion at the glomerulus.","article;chelation;copper urine level;drug excretion;model;rat;theoretical study;Wilson disease;1,2 bis(3,5 dioxo 4 methylpiperazin 1 yl)ethane;1,2,4 triazole;benzothiazole;copper;dimercaprol;dithiothreitol;edetate disodium;ethylenediamine;icrf 158;kojic acid;levodopa;meconic acid;mercaptoimidazole;methenamine;penicillamine;razoxane;spermine;thiol x;thiol y;tiopronin;trientine;tris(aminoethyl)amine;unclassified drug","Gibbs, K.;Walshe, J. M.",1977,,,0,0,
3145,Prevention of the ocular manifestations in inborn errors of metabolism,"Most of the inborn errors of metabolism can only be prevented by genetic counseling or abortion after prenatal diagnosis. In homocystinuria it is, nevertheless, possible to obtain a therapeutic result by a diet poor in methionine and rich in cystine, associated with pyridoxine, in Wilson's disease by penicillamine, in abetalipoproteinemia by vitamin A and in galactosemia or galactokinase deficiency by a diet without galactose.",abetalipoproteinemia;diagnosis;diet;etiology;eye;galactosemia;homocysteine urine level;inborn error of metabolism;Lowe syndrome;major clinical study;prevention;therapy;Wilson disease;cystine;galactose;methionine;penicillamine;pyridoxine;retinol,"Francois, J.",1977,,,0,0,
3146,Effects and side effects of penicillamine. [German],"At present, D-penicillamine treatment is considered indicated not only in Wilson's disease but also in many other diseases, most of them belonging to the group of auto-immune diseases. A brief survey is given of the possible mechanism of action of the substance. Side effects so far observed are listed. Since side effects occur in a large proportion of the cases and are not always reversible but sometimes also fatal, it is advocated that the drug, in spite of its mostly good effects on the basic disease, should be administered only on strict indications, when other methods of treatment are not possible. Regular check-ups should be provided for.",adverse drug reaction;autoimmune disease;bone marrow depression;drug therapy;liver toxicity;nephrotoxicity;polymyositis;polyneuropathy;proteinuria;rheumatoid arthritis;scleroderma;skin toxicity;systemic lupus erythematosus;therapy;Wilson disease;penicillamine,"Runge, E.;Tellkamp, F.",1977,,,0,0,
3147,"Renal tubular acidosis in Wilson's disease: Characteristics, mechanisms and implications",,etiology;kidney;kidney acidifying capacity;kidney tubule acidosis;major clinical study;Wilson disease;penicillamine,"Leu, M. L.;Strickland, G. T.",1977,,,0,0,
3148,Treatment of hepato-cerebral degeneration (Wilson's disease). [German],"Among the diseases with extrapyramidal disorder syndromes, hepatocerebral degeneration (synonyms are Morbus Wilson and Strumpell-Westphalic Pseudosclerosis) occupies a special place while here the cause of problems lies in a recessively inherited metabolic disorder. It can be effectively influenced by consequent medicamentous therapy and diet. The disorder is quite rare: it is estimated that only a total of 100 patients in the entire GFR require such specific treatment. A basic feature of the anticopper regime lies in the changeover to a low copper diet. If possible, copper intake should not exceed the I mg per day level. Over the last 15 years, D-Penicillamin (Metalcaptase) has been the preferred agent in medicamentous treatment of hepatocerebral degeneration. The substance mobilises the copper stored in organs and prevents further storage so that copper is transformed in soluble chelate complexes which can then be discharged via the kidneys. The substance should be administered slowly; as a rule, 0.9 to I.8 g are required daily. In experiments, an antagonism was established between D-Penicillamin and vitamin B-6 (Pyridoxin). As a result, latent vitamin B-6 deficiencies were observed under D-Penicillamin therapy. Consequently, an additional administration of 40 mg vitamin B-6 per day is recommended, particularly in those patients which already showed signs of a latent or manifest hypovitaminosis before treatment started (21 references).",adverse drug reaction;article;diet;drug therapy;immune complex nephritis;liver disease;rash;therapy;Wilson disease;metal captase;penicillamine;potassium sulfide;unclassified drug,"Fouquet, H.;Broser, F.",1977,,,0,0,
3149,Two cases of verruciform perforating elastoma after prolonged administration of penicillamine in Wilson's disease. [French],,adverse drug reaction;Darier disease;drug therapy;elastoma;oral drug administration;therapy;verruciform perforating elastoma;Wilson disease;penicillamine,"Sfar, Z.;Lakhoua, H.;Hafsia, M.;Amor, R. B.;Mahfoudh, H.;Hamza, B.;Abdallah, C. B.",1977,,,0,0,
3150,Elastosis perforans serpiginosa induced by penicillamine. Electron microscopic observations,"A 22-yr-old male patient with Wilson disease, under prolonged treatment with penicillamine, developed lesions of elastosis perforans serpiginosa (EPS). Examination of biopsy specimens by light microscopy revealed the characteristic changes of EPS. Examination by transmission electron microscopy revealed structural changes in the elastic fibers not previously described. The appearance of the lesions by scanning electron microscopy is described for the first time. It is suggested that penicillamine induced EPS may be morphologically distinct from the idiopathic form.",adverse drug reaction;drug eruption;drug therapy;elastic fiber;elastosis perforans serpiginosa;electron microscopy;oral drug administration;scanning electron microscopy;therapy;Wilson disease;penicillamine,"Kirsch, N.;Hukill, P. B.",1977,,http://dx.doi.org/10.1001/archderm.113.5.630,0,0,
3151,Acute erosive gastritis induced by D penicillamine: its prevention by mylanta II. Metiamide and cimetidine,,clinical study;drug antagonism;drug comparison;drug therapy;erosive gastritis;major clinical study;rat;theoretical study;therapy;Wilson disease;cimetidine;metiamide;penicillamine,"Mann, N. S.",1977,,,0,0,
3152,Arthropathy of Wilson's disease. Study of clinical and radiological features in 32 patients,"The principal clinical features and radiological findings relating to the locomotor system have been studied in 32 consecutive hospital admissions of patients with Wilson's disease. 5 of these patients were recently diagnosed and had as yet received no treatment, while 27 were routine admissions for follow-up and biochemical supervision of their illness. No patient was specifically included or excluded from the series because of the presence or absence of locomotor symptoms. The most common radiological abnormality was a generalized increase of radiolucency, interpreted as skeletal demineralization (21 cases), followed by premature osteoarthrosis (8 cases). Changes in the spine were common and included osteochondritis, reduction of intervertebral joint spaces, osteoarthrosis, and a tendency to squaring of vertebral bodies. Other bony changes included fluffy irregularity of femoral trochanters, osteochondritis dissecans of the knees, osteophytic protrusions at bone ends, and bunches of tongue-like osteophytes at joint margins. The symptoms associated with these radiological abnormalities comprised back pain and stiffness with restricted movement, pain and stiffness of knees, hips, and wrists, and tenderness to pressure over margins of affected joints. Joint hypermobility was also observed in 9 patients. Episodes of acute polyarthritis with serological changes were seen in 5 cases; all these episodes appeared to be related directly to treatment with penicillamine.",arthritis;arthropathy;demineralization;diagnosis;joint mobility;joint stiffness;major clinical study;osteochondritis dissecans;pain;polyarthritis;skeleton;spondylosis;therapy;Wilson disease;penicillamine,"Golding, D. N.;Walshe, J. M.",1977,,,0,0,
3153,The use of radioactive copper and zinc in psychiatric diagnosis. [French],"Three conclusions may be drawn from the results supplemented by some known data. Administration of the phenothiazines results in rise of the amount of <sup>65</sup>Zn taken up by certain limbic structures of the brain. Cassano found a high concentration of <sup>35</sup>S labelled chlorpromazine in the rat hippocampus and Ashby an increase in carbonic anhydrase in the brains of rats thus treated and fall of this enzyme in the brain of untreated schizophrenics. There thus probably exists a cause and effect relation between, on the one hand, the changes in the level of Zn and carbonic anhydrase in the encephalon (mesencephalon) in schizophrenics and, on the other, the influence of the phenothiazines on the distribution of encephalic zinc. Will it then be possible to claim that a lack of a zinc compound produces the mental illness and that the phenothiazines have favorable effect by raising the zinc level?",anxiety;article;brain;diagnosis;drug therapy;hysteria;major clinical study;neurosis;rat;schizophrenia;theoretical study;Wilson disease;acetate cupric cu 64;chlorpromazine;chlorpromazine s 35;copper;perphenazine;phenathiazine;radioisotope;thioridazine;unclassified drug;zinc;zinc chloride zn 65,"Czerniak, P.;Zwas, S. T.",1976,,,0,0,
3154,Renal lesion in Wilson's disease. Electron microscopic findings in hepatic glomerulosclerosis and electron microanalysis of copper in the renal lesion (Japanese). [Japanese],"Kidney and liver biopsies from 2 patients with abnormal urinary findings were studied by light, fluorescent and electron microscopy, in addition to electron microanalysis. A 10 yr old boy had liver cirrhosis with prominent vacuolar degeneration. Percutaneous renal biopsy was performed twice, before and after the administration of D-penicillamine. The kidney showed glomerulosclerosis. Light microscopy showed a prominent increase of the mesangial matrix with slight cell proliferation and focal thickening of the glomerular basement membrane (GBM). Electron microscopy confirmed these findings and showed electron-dense deposits in the subendothelial areas and mesangial matrix as well as the socalled 'moth-eaten appearance'. Thickening of the GBM and mesangial interposition were evident. IgG and IgM were present in the glomeruli; IgG and fibrinogen were seen in the mesangial areas. After O penicillin treatment, granular staining of IgG, IgM, IgA and fibrinogen was seen in the mesangium and along the GBM. On electron microanalysis a high concentration of copper was apparent in the lysosome-like dense bodies in the proximal tubule cells. No copper was obtained from the glomeruli. The second case was that of a 6 yr old boy. In the blood IgA was increased; C<inf>3</inf> and C<inf>4</inf> were normal. The findings in the glomeruli by the light microscope were not much different from those in case 1: ultrastructurally an increase of the mesangial matrix and thickening of the GBM were evident. However, the electron-dense deposits and the 'moth-eaten appearance' were absent. By immunofluorescence, only IgG was stained in the mesangial area and faintly along the glomerular capillary walls. Copper could not be demonstrated. The results lead to some hypotheses. Hyperimmunoglobulinemia and low levels of serum complement components may be caused by liver failure (case 1). Morphologic glomerular changes were apparently not caused by direct accumulation of serum copper according to copper microanalysis in the tissue; immunologic mechanisms may play a role, though no antigen was identified. Lysosomes have a certain function in copper metabolism of the proximal tubular epithelium. It is conceivable that hyperimmunoglobulinemia and low levels of serum C<inf>3</inf> and C<inf>4</inf> may be involved in the pathogenesis of nephrosclerosis, although they were found only in case 1.",child;diagnosis;electron microscopy;glomerulosclerosis;glomerulus basement membrane;histology;in vitro study;kidney disease;major clinical study;mesangium;methodology;therapy;Wilson disease;immunoglobulin;penicillamine,"Fukunishi, Y.;Fujisawa, S.;Shimizu, S.",1976,,,0,0,
3155,Reactions of D penicillamine with copper in Wilson's disease,,drug absorption;major clinical study;methodology;spectroscopy;urine;Wilson disease;X ray analysis;copper;penicillamine,"Rupp, H.;Weser, U.",1976,,,0,0,
3156,Drugs for rare diseases,,drug therapy;therapy;Wilson disease;penicillamine;trientine,Anonymous,1976,,,0,0,
3157,Pregnancy in penicillamine treated patients with Wilson's disease,,drug dose;drug response;drug therapy;fetus;oral drug administration;pregnancy;therapy;Wilson disease;penicillamine,"Marecek, Z.;Graf, M.",1976,,,0,0,
3158,D penicillamine induced IgA deficiency in Wilson's disease,,adverse drug reaction;drug therapy;immunofluorescence;immunoglobulin deficiency;major clinical study;oral drug administration;plasma cell;Wilson disease;immunoglobulin A;penicillamine;phenytoin,"Proesmans, W.;Jaeken, J.;Eeckels, R.",1976,,,0,0,
3159,Purification and use of triethylenetetramine trihydrochloride for treatment of patients with Wilson's disease (Dutch). [Dutch],,chelation;clinical study;diuresis;drug screening;drug synthesis;drug therapy;infrared spectrometry;major clinical study;mass spectrometry;therapy;Wilson disease;copper;trientine,"Juul Christensen, E. K.;Que, G. S.;Steenhoek, A.",1976,,,0,0,
3160,D penicillamine and hemolytic anemia,,drug indication;drug therapy;hemolytic anemia;major clinical study;therapy;thrombocytopenia;Wilson disease;glucose 6 phosphate dehydrogenase;penicillamine,"Harrison, E. E.;Hickman, J. W.",1976,,,0,0,
3161,Penicillamine. [French],,cystinuria;drug therapy;immunosuppressive treatment;lead poisoning;polyarthritis;therapy;Waldenstroem macroglobulinemia;Wilson disease;alkylating agent;antimetabolite;chlorambucil;edetate calcium disodium;penicillamine,"Sonnet, J.",1976,,,0,0,
3162,Studies on D penicillamine metabolism in cystinuria and rheumatoid arthritis: isolation of S methyl D penicillamine,"An unknown metabolite of D penicillamine found in the urine of patients receiving the drug has been isolated by ion exchange chromatography. It was identified as S methyl D penicillamine by mass spectrometry and its structure was confirmed by synthesis. In subjects receiving D penicillamine for treatment of cystinuria and rheumatoid arthritis 4 and 8 per cent respectively of the dose was methylated. The total percentage of the D penicillamine dose excreted (as cysteine penicillamine plus penicillamine disulphide plus S methyl D penicillamine) was 40 and 34 per cent in cystinuria and rheumatoid arthritis respectively. The findings in two cases of Wilson's disease were similar to those in rheumatoid arthritis. In studies on four cystinuria patients an average of 12 per cent of the administered D penicillamine was recovered in the feces mainly as penicillamine disulphide. However, only between 42 and 53 per cent of the dose was identified in the urine and feces, so that approximately 50 per cent of the administered drug was unaccounted for. D Penicillamine caused a 32 per cent reduction in the urinary excretion of cysteine residues in cystinuria but a 400 per cent increase in their excretion in rheumatoid arthritis.",article;cystinuria;drug analysis;drug blood level;drug excretion;drug identification;drug metabolism;drug screening;drug synthesis;drug urine level;feces;in vitro study;ion exchange chromatography;major clinical study;mass spectrometry;methodology;methylation;pharmacokinetics;plasma;rheumatoid arthritis;theoretical study;therapy;urine;Wilson disease;drug metabolite;penicillamine;penicillamine cysteine disulfide;penicillamine disulfide;s methylpenicillamine;unclassified drug,"Perrett, D.;Sneddon, W.;Stephens, A. D.",1976,,http://dx.doi.org/10.1016/0006-2952%2876%2990210-0,0,0,
3163,The effect of long term treatment with d penicillamine on the humoral immune response in patients with Wilson's disease,"The levels of immunoglobulins and antibodies to CA antigen (an antigen common to Enterobacteriaceae) and to O S. typhi antigen were determined in 13 patients with Wilson's disease not treated with d penicillamine and in 8 treated with this drug over 2 years. It was found that in the treated patients, levels of immunoglobulins as well as antibodies decreased, which suggests that d penicillamine exerts an inhibitory effect on the humoral immune response.",drug therapy;immune response;immunity;major clinical study;therapy;Wilson disease;antibody;antigen;immunoglobulin;immunoglobulin A;immunoglobulin G;immunoglobulin M;penicillamine,"Czlonkowska, A.",1976,,,0,0,
3164,A case of Wilson's disease: hemodynamic evaluation. [Italian],"After diagnosis of Wilson's disease in a cirrhotic patient, he is subjected to therapy with L Dopa and d penicillamine. The haemodynamic evaluation, carried out before and after the therapeutic operation, shows an improvement in normodynamic direction of the primitive hyperdynamic state. The simultaneous improvement in the neurological symptomatology offers a starting point for some therapeutic and clinical considerations.",diagnosis;in vitro study;liver cirrhosis;major clinical study;methodology;therapy;Wilson disease;levodopa;penicillamine,"Sacco, R.;Bianco, A.;Cagossi, M.",1976,,,0,0,
3165,Episodic mental disorders in Wilson's disease (Japanese). [Japanese],,acting out;behavior disorder;confession;delirium;diagnosis;etiology;frustration;hallucination;major clinical study;psychosis;Wilson disease;penicillamine,"Fukuda, K.;Matsue, Y.;Ishii, A.",1976,,,0,0,
3166,Glomerulonephritis due to D penicillamine. [German],"Within 2 yr a total of 12 patients with proteinuria after D-penicillamine therapy were examined clinically, serologically and by renal biopsy (light microscopy, immunohistology, transmission and scanning electronic microscopy). The light microscopic, immunohistologic and electron microscopic assessments were made independently in 3 different institutes. In a table the renal symptoms of the patients at the time of the renal biopsy are summarized, and in a second table the degree of the proteinuria is compared with the histologic diagnoses. In all cases a 'mesangioproliferative' glomerulonephritis somewhat resembling an LE nephritis was found. The interstitium contained infiltrates of lymphocytes and plasma cells, often with hyaline vacuoles, and foam cells as the expression of the lipoid nephrosis. There was no indication of the existence of an amyloidosis. The immunohistology corresponded to the picture of an immune complex nephritis. Transmission electron microscopy revealed an irregular thickening of the glomerulus basement membrane. Neither a diffuse thickening of this membrane as in typical membranous glomerulonephritis nor protuberances resembling spikes could be found. The mesangial matrix was broadened by increased cell proliferation. The scanning electron microscope, particularly in cases with a strong proteinuria, showed partial shrinkage and distortion of the podocyte processes by bud-like or shell-shaped outgrowths. Podocytic changes are probably not specific. The clinical course of the disease was favourable. On the basis of the renal biopsies (for a part marked mesangial cell proliferation and an increase of PAS-positive matricial substances) the D-penicillamine glomerulopathy is held to be special form of 'mesangioproliferative' glomerulonephritis, because as a rule all of the glomeruli had undergone inflammatory changes and electron microscopy showed a relatively strong proliferation in the mesangium. This, as well as the regressive thickening of the basement membrane by subepithelial depositions, is against a classification of this LE-like nephropathy among the typical forms of membranous or perimembranous glomerulonephritis. Etiologically it is not improbable that this D-penicillamine glomerulonephritis is a drug-induced immune-complex nephritis similar to a gold nephropathy. In favor of this supposition are: the immunohistologic picture with deposits of IgG and complement, the periglomerular and periarteriolar round cell infiltrations, and the obvious lack of dose dependence. Antibodies against D-penicillamine are demonstrable, but their pathogenetic significance is not clear. The greater prevalence of renal damage by D-penicillamine in diseases with a normal copper metabolism in comparison with Wilson's disease, may possibly be explained by the fact that D-penicillamine after chelate formation with copper acts less immunogenically.",adverse drug reaction;glomerulonephritis;histology;immune complex disease;immunoglobulin deposition;mesangium;nephrotoxicity;oral drug administration;proliferative glomerulonephritis;proteinuria;therapy;penicillamine,"Brass, H.;Genth, E.;Hartl, P. W.;Bauerdick, H.;Buss, H.;Lapp, H.;Heintz, R.",1976,,,0,0,
3167,Wilson disease. [French],"This boy was admitted to the hospital at the age of 11 months, early in December, 1973 for the investigation of a neurological syndrome with hepatosplenomegaly. The case illustrates the tendency of this disease to advance intermittently, with occasional rapid aggravation. It also illustrates the efficacy of D penicillamine and the occasional difficulty of finding the dosage which will be both effective and well tolerated.",adverse drug reaction;drug therapy;inborn error of metabolism;leukopenia;major clinical study;oral drug administration;serum;therapy;urine;Wilson disease;copper;penicillamine,"Hoppeler, A.;Hovasse, M.;Creusot, G.",1976,,,0,0,
3168,Treatment of Wilson's disease in children Five case report. [French],,child;cupremia;hemostasis;hypersplenism;liver cirrhosis;major clinical study;therapy;Wilson disease;copper;penicillamine,"Landrieu, P.;Choulot, J. J.",1976,,,0,0,
3169,Skin lesions induced by penicillamine: occurrence in a patient with hepatolenticular degeneration (Wilson disease),"Penicillamine is a metabolite of penicillin, is antigenic, and is, thus, allergenic in man. The adverse side effects of this drug, however, are related not only to its allergenicity, but also to its effect on connective tissue and possibly on the chelation of heavy metals. Since side effects occur frequently with penicillamine, and since the drug is being used to treat numerous disorders, the following case is reported. A 41 yr old patient with hepatolenticular degeneration (Wilson disease), who had been treated for 15 yr with penicillamine, developed small white papules at sites of venipuncture in the antecubital fossae and at surgical suture sites. Histologically, these papules showed connective tissue degeneration in the dermis. The changes most likely resulted from the effect of penicillamine on new connective tissue formation at the sites of injury. The patient also developed crinkling of the skin of her face and neck while on the penicillamine regimen, and these changes were attributed, at least in part, to the effects of this drug on connective tissue.",adverse drug reaction;connective tissue;drug eruption;drug therapy;histology;oral drug administration;papule;skin;skin toxicity;therapy;Wilson disease;penicillamine;pyridoxine,"Greer, K. E.;Askew, F. C.;Richardson, D. R.",1976,,http://dx.doi.org/10.1001/archderm.112.9.1267,0,0,
3170,Nephrotic syndrome following penicillamine therapy in Wilson's disease. [German],"In a 33-yr-old man with Wilson's disease, a nephrotic syndrome appeared as a severe complication under penicillamine therapy. Under strong observation and exact controls of protein in the urine, leucocytes, differential blood picture and thrombocytes after interruption of the medication and retrogression of the side effects, a retarding new stabilisation on penicillamine can take place. Other side effects of penicillamine observed, as well as control measures under a long-term treatment with penicillamine, are briefly discussed. .",adverse drug reaction;clinical study;drug therapy;major clinical study;nephrotic syndrome;oral drug administration;therapy;Wilson disease;penicillamine,"Hampel, R.;Meng, W.;Kallwellis, G.",1976,,,0,0,
3171,Wilson's disease. Hepato cerebral degeneration. [German],,clinical study;diagnosis;drug therapy;etiology;genetics;histology;histopathology;pathogenesis;prevention;therapy;Wilson disease;ceruloplasmin;dimercaprol;penicillamine,"Sternlieb, I.",1976,,,0,0,
3172,Insufficiency of the exocrine pancreas in Wilson's disease. [German],"The function of the exocrine pancreas was examined by the secretin pancreozymin test in 3 patients with Wilson's disease. In all cases a partial insufficiency was found. At the time of investigation the patients were 6 7/12, 11 6/12 and 21 yr old. The youngest was exained before therapy with D Penicillamin. The authors suppose that storage of copper in lysosomes causes a cytotoxic damage of the exocrine part of the pancreas requiring substitution therapy in advanced cases.",etiology;major clinical study;pancreas function;Wilson disease;copper;penicillamine,"Osswald, P.;Niessen, K. H.",1976,,http://dx.doi.org/10.1007/BF01469306,0,0,
3173,The diagnostic application of specific anti procollagen sera. I. Analysis of skin biopsies,"Antisera were prepared in rabbits against mature calf skin collagen (type I) and a polypeptide characteristic for calf skin procollagen (type I). The latter peptide is attached to the aminoterminal end of the alpha chains and cleaved off during normal maturation by a specific enzyme, procollagen peptidase. for the present study procollagen was isolated from the skin of calves with an inborn deficiency of procollagen peptidase, a disease called dermatosparaxis. The antisera to mature collagen and procollagen were rendered specific by appropriate immunoadsorption procedures. These sera show a strong crossreaction with human skin collagen and procollagen. While anti collagen sera produced indirect immunofluorescent staining of the whole dermis, anti procollagen sera only react with the uppermost dermal layer (stratum papillare) of unfixed frozen sections of normal human skin biopsies. Frozen unfixed sections of skin biopsies from 50 patients with various diseases were analyzed in indirect immunofluorescence tests with antiprocollagen sera. In 19 cases, material from uninvolved skin areas were also available for study. Skin from patients with connective tissue diseases (systemic lupus erythematosus, dermatomyositis, scleroderma) reacts like normal skin. Skin from patients with psoriasis vulgaris and lichen planus shows broad subepithelial zones of procollagen fluorescence. Keloids display very weak or no procollagen immunofluorescence in several instances. In 3 studied cases with prolonged local corticoid treatment a normal procollagen immunofluorescence pattern reappeared. Biopsies from one case of Wilson's disease under prolonged D penicillamine therapy and one case of epidermolysis bullosa also lacked reactivity with anti procollagen sera. Uninvolved skin of all patients revealed normal procollagen immunofluorescence. It is concluded that immunofluorescence studies with specific antisera to procollagen provide a simple and exact tool for the localized analysis of collagen metabolism.",article;cattle;connective tissue disease;diagnosis;immunofluorescence;in vitro study;major clinical study;methodology;skin biopsy;skin disease;theoretical study;collagen antigen;procollagen;unclassified drug,"Wick, G.;Kraft, D.;Kokoschka, E. M.;Timpl, R.",1976,,http://dx.doi.org/10.1016/0090-1229%2876%2990109-4,0,0,
3174,D penicillamine in the treatment of rheumatoid arthritis and progressive systemic sclerosis,"D Penicillamine (B'B'' dimethylcysteine) is a drug widely known for its clinical therapeutic benefit in the treatment of Wilson's disease and cystinuria. A number of recent studies have demonstrated that penicillamine may be therapeutically active in other diseases including rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), morphea and active chronic hepatitis, as well as acting as a chelator of a number of heavy metals. The increasing number of therapeutic indications for D penicillamine therapy need to be clearly defined and its ill effects plainly identified. This review concentrates on the present value of this drug in the treatment of rheumatoid arthritis and progressive systemic sclerosis.",clinical study;drug therapy;drug toxicity;major clinical study;proteinuria;review;rheumatoid arthritis;scleroderma;systemic sclerosis;therapy;thrombocytopenia;penicillamine,"Davis, P.;Bleehen, S. S.",1976,,http://dx.doi.org/10.1111/j.1365-2133.1976.tb05174.x,0,0,
3175,Immunological disturbances in Wilson's disease with reference to the effect of treatment with D penicillamine (Polish). [Polish],,clinical study;drug efficacy;drug therapy;immunology;major clinical study;therapy;Wilson disease;immunoglobulin;penicillamine,"Czlonkowska, A.",1976,,,0,0,
3176,Diffuse alveolitis as complication of penicillamine treatment for rheumatoid arthritis,"Penicillamine is as effective as gold when used as an antirheumatic drug. Side effects may occur, however, the best recognised being marrow suppression, the nephrotic syndrome, abnormalities of taste, rashes, and gastrointestinal disturbances. All are usually reversible on stopping treatment. Nevertheless, deaths have occurred, and recently three cases of Goodpasture's syndrome were reported in patients taking 1 to 3.5 g penicillamine daily for Wilson's disease over 2 to 3.5 yr. The author reports diffuse alveolitis as a complication of treatment with penicillamine in a patient given small doses for rheumatoid arthritis.",adverse drug reaction;drug induced disease;drug therapy;dyspnea;lung alveolitis;lung function;oral drug administration;rheumatoid arthritis;therapy;azathioprine;penicillamine,"Eastmond, C. J.",1976,,,0,0,
3177,Red cell aplasia following prolonged D penicillamine therapy,"Red cell aplasia developed in a case of Wilson's disease following an increase in D penicillamine dosage after 14 years' treatment. In vitro study of the effect of D penicillamine on <sup>59</sup>Fe incorporation by marrow cells did not suggest that the patient's erythropoiesis was particularly sensitive to D penicillamine or determine the mechanism of drug toxicity. However, three weeks after the drug was withdrawn, evidence of marrow regeneration was apparent, and within 10 weeks the haemoglobin had returned to normal. The patient has subsequently remained asymptomatic on an alternative chelating agent, triethylenetetramine dihydrochloride.",adverse drug reaction;aplastic anemia;clinical study;drug therapy;erythrocyte aplasia;erythropoiesis;major clinical study;oral drug administration;review;therapy;Wilson disease;iron;penicillamine;radioisotope;thymidine h 3;unclassified drug,"Gollan, J. L.;Hussein, S.;Hoffbrand, A. V.;Sherlock, S.",1976,,,0,0,
3178,Pemphigus foliaceus induced by penicillamine,"Pemphigus occurring during penicillamine treatment of Wilson's disease was first reported in France and later shown to occur in rheumatoid arthritis. The patient may have pemphigus vulgaris or pemphigus foliaceus, and most improve when penicillamine is withdrawn. In some cases, however, the rash persists and is difficult to control. Since then this complication has become well recognised by British dermatologists. The authors describe 7 patients who developed pemphigus.",adverse drug reaction;drug eruption;drug therapy;histology;oral drug administration;pemphigus foliaceus;pemphigus vulgaris;rheumatoid arthritis;therapy;azathioprine;penicillamine;prednisolone,"Marsden, R. A.;Ryan, T. J.;Vanhegan, R. I.",1976,,,0,0,
3179,Wilson's disease (case report). [Spanish],,child;diagnosis;major clinical study;serum;therapy;Wilson disease;ceruloplasmin;copper;penicillamine,"Danus, O.;Larrain, F.;Urbina, A. M.",1975,,,0,0,
3180,Pregnancy in penicillamine treated patients with Wilson's disease,"In women with untreated Wilson's disease amenorrhea and spontaneous abortions are frequent, and the probability of marriage is reduced by the neurologic and psychiatric disturbances of the disorder. Treatment with D penicillamine has dramatically altered the course of this illness so that a normal reproductive life is the rule rather than the exception. None of 18 women with Wilson's disease, who received penicillamine during 29 pregnancies and delivered 29 normal infants, suffered any exacerbation of their disease during pregnancy. Of two women with Wilson's disease in whom penicillamine treatment was interrupted before or during pregnancy, one manifested evidence of progressive hepatic decompensation in the third trimester and died of liver disease two years later. In the other severe hemolytic anemia occurred in the second trimester, seven months after penicillamine was discontinued. The conclusion is drawn that penicillamine treatment, continued throughout pregnancy, protects the mother against relapse of Wilson's disease and carries no risk for the fetus. However, pregnancy is not advisable in patients with Wilson's disease who have bled from esophageal varices, or who manifest hepatic insufficiency.",drug therapy;major clinical study;pregnancy;therapy;Wilson disease;penicillamine,"Scheinberg, I. H.;Sternlieb, I.",1975,,,0,0,
3181,Prevention of Wilson's disease: present state. [French],,diagnosis;fatty liver;liver cirrhosis;liver fibrosis;therapy;Wilson disease;ceruloplasmin;penicillamine;trientine,"Sternlieb, I.",1975,,,0,0,
3182,D penicillamine in dermatology: influence on enzymatic activities of human skin in vitro,"By in vitro assay, 6 important enzymatic activities of human skin homogenates were determined following an incubation with D penicillamine in concentrations between 10<sup>-4</sup> and 10 mg/ml, i.e. 67X10<sup>-5</sup> and 67 mM/1. The following enzymatic activities were recorded: lactate dehydrogenase (LDH), glucose 6 phosphate dehydrogenase (G 6 PDH), glyceraldehyde 3 phosphate dehydrogenase (GAPDH), alkaline phosphatase (AP), acid phosphatase (AcP), and 'leucine aminopeptidase' (LAP). A dose dependent activation by D penicillamine occurred in the case of G 6 PDH and AcP activities, a dose dependent inhibition by D penicillamine was found with AP and GAPDH activities. LDH and LAP activities remained unchanged in the presence of D penicillamine in concentrations up to 10 mg/ml (67 mM/l). From the data of pharamacokinetic studies in rats it may be concluded that concentrations of D penicillamine which influence enzymatic activites may easily be reached in vivo, under the conditions of treating rheumatoid arthritis and Morbus Wilson. The biochemical actions of D penicillamine are briefly discussed with special regard to dermatological therapy and dermatological unwanted side effects.",human;in vitro study;normal human;rheumatoid arthritis;theoretical study;Wilson disease;acid phosphatase;alkaline phosphatase;cytosol aminopeptidase;glucose 6 phosphate dehydrogenase;glyceraldehyde 3 phosphate dehydrogenase;lactate dehydrogenase;oxidoreductase;penicillamine,"Raab, W.;Gmeiner, B.",1975,,http://dx.doi.org/10.1007/BF00561539,0,0,
3183,The kinetics of copper uptake by the liver in Wilson's disease studied by a whole body counter and a double labelling technique,"The hepatic uptake of <sup>64</sup>Cu in the body was studied by whole body counting in normal subjects, homozygotes, and heterozygotes of Wilson's disease. Special attention was paid to the copper kinetics during the first hour after injection of <sup>64</sup>Cu. Two different measuring techniques were used simultaneously: one collimated NaI(Tl) crystal was in a fixed position over the liver, the counts being recorded by a single channel analyser connected to a multi channel analyser in a multi channel scaling mode; and a second collimated crystal makes scanning movements along the body axis, the counts being recorded by a multi channel analyser in a multi spectrum scaling mode. With this procedure it is possible to use a double nuclide labelling technique by means of which both the <sup>64</sup>Cu values for an organ can be corrected for the <sup>64</sup>Cu blood content in the region of interest, and information can be obtained on the actual dynamic <sup>64</sup>Cu movement in the body.",clinical study;diagnosis;drug blood level;heterozygote;heterozygote detection;intravenous drug administration;liver;major clinical study;methodology;pharmacokinetics;whole body scintiscanning;Wilson disease;chromium 51;copper;copper 64;penicillamine;radioisotope,"Guenther, K.;Loessner, V.;Loessner, J.;Biesold, D.",1975,,,0,0,
3184,Results of electroencephalographic and familial studies in cases of Wilson's disease. [German],,diagnosis;electroencephalography;etiology;major clinical study;spike;spike wave;Wilson disease;penicillamine,"Sack, G.;Loessner, J.;Bachmann, H.",1975,,,0,0,
3185,Treatment of acute and chronic liver disease as well as several malabsorption syndromes with 2 mercaptopropionylglycine MPG (Thiola). [German],,alcoholism;drug efficacy;drug indication;drug therapy;hepatitis;liver cirrhosis;liver disease;malabsorption;oral drug administration;therapy;virus hepatitis;Wilson disease;azathioprine;chloramphenicol;cortisone;fluorouracil;mercaptopurine;penicillamine;phenylbutazone;placebo;tiopronin,"Markoff, N. G.",1975,,,0,0,
3186,Effects and side effects of D penicillamine. [German],"Penicillamine is a product common to all penicillins. It inhibits collagen synthesis and also has immunosuppressive and cytostatic action. Clinically, it was first used successfully in Wilson's disease. It has also been found of value in the treatment of heavy metal poisoning, in cystinuria where it can be expected to dissolve cystine stones, in chronic aggressive hepatitis, pulmonary fibrosis and scleroderma. Its most usual indication is in rheumatoid arthritis. Side effects are common and the most important include renal damage, bone marrow depression and a lupus erythematosus like reaction. Recently, a myasthenia gravis like syndrome has been reported which clears when the drug is discontinued.",adverse drug reaction;bone marrow depression;chronic active hepatitis;collagen synthesis;cystinuria;cytostasis;drug intoxication;drug therapy;gastrointestinal symptom;immunosuppressive treatment;lung fibrosis;nephrotoxicity;review;rheumatoid arthritis;scleroderma;skin allergy;teratogenesis;therapy;Wilson disease;antinuclear antibody;penicillamine,"Perings, E.;Junge, U.",1975,,,0,0,
3187,Penicillamine. [German],,adverse drug reaction;cystinuria;drug contraindication;drug dose;drug indication;therapy;Wilson disease;penicillamine;pyridoxine,"Hoerig, C.",1975,,,0,0,
3188,"Origins, clinical features and treatment of extrapyramidal motor disturbances. [German]","Noxious factors capable of irritating structures of the extrapyramidal motor system can become the cause of a series of precisely defined neurological syndromes. A review is given of the current state of basic research, the clinical symptomatology and therapeutic possibilities in this group of diseases.",athetosis;ballism;chorea;clinical study;dystonia;extrapyramidal syndrome;major clinical study;myoclonus;parkinson tremor;parkinsonism;therapy;Wilson disease;amantadine;atropine;benserazide plus levodopa;benzatropine mesilate;biperiden;bupranolol;butyrophenone;butyrophenone derivative;cyproheptadine;diazepam;etilefrine;fludrocortisone;haloperidol;levodopa;metoclopramide;penicillamine;perphenazine;phenothiazine derivative;phenytoin;procyclidine;propranolol;pyridoxine;reserpine derivative;scopolamine;trihexyphenidyl;vasopressin,"Voeller, G. W.;Deze, J.",1975,,,0,0,
3189,Recent acquisitions in the treatment of Wilson's disease. Clinical data. [Italian],"A case of Wilson's disease in a 16 yr old boy is reported. Upon first admittance, the patient presented an extrapyramidal syndrome, a left hemiparesis, dystonia, cirrhogenous hepatopathy and a clearly evident Kayser Fleischer ring. After undergoing penicillin therapy (20 mg/kg day), the patient was followed up for a period of 4 1/2 yr, periodic controls being taken of the clinical picture and haematologic and laboratory examinations. On the basis of literature data, the various therapeutical possibilities in Wilson's disease are discussed. Personal experience points to the great improvement in the boy's general conditions and the neurological picture observed following sustained penicillin therapy. It is also proposed that doses be reduced to below those commonly used, at the same time increasing the duration. This serves to reduce the onset of side effects which sometimes lead to the suspension of treatment. Finally, the fundamental importance of early diagnosis for the prevention of the progressive disability typical of the disease is pointed out.",afibrinogenemia;clinical study;dose response;drug response;drug therapy;dystonia;extrapyramidal syndrome;fibrinogen blood level;hemiparesis;kayser fleischer ring;liver disease;major clinical study;therapy;Wilson disease;fibrin;fibrinogen;penicillamine;penicillin G,"Rigardetto, R.;Trevisio, A.",1975,,,0,0,
3190,Clinical forms and treatment of cirrhosis. [French],,adverse drug reaction;alcoholism;ascites;bacterial infection;clinical study;drug therapy;edema;esophagus varices;etiology;gastrointestinal hemorrhage;hemochromatosis;hepatitis;jaundice;liver cirrhosis;survey;Wilson disease;alcohol;deferoxamine mesylate;lactulose;levodopa;neomycin;penicillamine,"Escourrou, J.;Izard, G.",1975,,,0,0,
3191,Metabolic diseases of genetic origin susceptible to treatment. [French],,"Crigler Najjar syndrome;cystinosis;cystinuria;diabetes insipidus;fibrous dysplasia;galactosemia;genetic disorder;goiter;hemochromatosis;hereditary fructose intolerance;histidinemia;homocysteine urine level;hyperlipoproteinemia;malabsorption;maple syrup urine disease;metabolic disorder;oral drug administration;phenylketonuria;rickets;therapy;thyroid gland;tyrosinemia;Wilson disease;3,4 bis(3 hydroxyphenyl)hex 3 ene derivative;amino acid;carbohydrate;clofibrate;colecalciferol;colestyramine;cortisone;cystine;deferoxamine mesylate;diuretic agent;mineralocorticoid;mucolytic agent;pancreas extract;penicillamine;phenobarbital;phosphoric acid;potassium sulfide;pyridoxine;thyroxine;unclassified drug",Anonymous,1975,,,0,0,
3192,Wilson's disease. A treatable liver disease in children,"Wilson's disease (hepatolenticular degeneration) often presents in childhood with liver disease alone and without neurological symptoms. Early recognition of this condition is of great importance because this is one treatment the few diseases of the liver for which effective treatmnt is available. The diagnosis of Wilson's disease can now be relatively easily established without having to wait for the development of the typical and clinicaly recognizable multi organ involvement. This is important for the practicing physician and pediatrician because these patients can now be effectively treated by the simple oral administration of a relatively nontoxic agent, D penicillamine. Whereas before, the untreated patients with Wilson's disease all died, they can now be restored to virtually normal health; they can live a normal life and a normal life span, provided the diagnosis is made and the treatment instituted early, before the development of irreparable damage to vital organs. The aim of this paper is to remind the clinician when Wilson's disease should be suspected in children, how to arrive at the diagnosis or to exclude it, and how to treat the patient once the diagnosis is made.",adverse drug reaction;behavior disorder;child;diagnosis;drug therapy;fever;hemolytic anemia;inheritance;liver biopsy;lymphadenopathy;nephrotic syndrome;rash;review;rickets;survey;systemic lupus erythematosus;therapy;Wilson disease;copper;copper 67;dimercaprol;penicillamine;radioisotope,"Sass Kortsak, A.",1975,,,0,0,
3193,Wilson's disease (hepatolenticular degeneration) of late adult onset. Report of a case,"Wilson's disease usually has its onset in childhood, adolescence, or early adulthood. The clinical picture of hepatic dysfunction without dysfunction of the central nervous system is more typical of the disease in the child or the adolescent than in the adult. We are presenting the case of a man whose age at onset of the disease was 55 years and who had the hepatic complications of Wilson's disease without clinical evidence of disease of the central nervous system. All patients with chronic hepatitis (chronic active liver disease) or cirrhosis of unknown etiology should be screened for the possibility of Wilson's disease. This screening should include slit lamp biomicroscopy for Kayser Fleischer rings, determination of serum ceruloplasmin concentrations, and measurement of 24 hour urinary excretion of copper. If doubt exist concerning the diagnosis, either a radiocopper kinetic study, using <sup>64</sup>Cu or <sup>67</sup>Cu, or, if the patient's condition permits, a liver biopsy with measurement of hepatic copper concentration should be done. The rubeanic stain of hepatic tissue for copper is unreliable in making or excluding the diagnosis of Wilson's disease.",article;chronic hepatitis;clinical study;diagnosis;drug therapy;kayser fleischer ring;liver cirrhosis;major clinical study;metabolism;onset age;serum;therapy;urine;Wilson disease;4 amino 2 methyl 1 naphthol;ceruloplasmin;copper;copper 67;penicillamine;radioisotope;unclassified drug,"Fitzgerald, M. A.;Gross, J. B.;Goldstein, N. P.;Wahner, H. W.;McCall, J. T.",1975,,,0,0,
3194,Molecular biology of copper. A circular dichroism study on copper complexes of thionein and penicillamine,"Chicken liver Cd, Zn thionein (metallothionein) was isolated from Cd pretreated chickens weighing 1 500 g. The native Cd, Zn thionein contained 9 g atoms of metals per 12 000 g of protein. Upon the addition of Cu(CH<inf>3</inf>CN)<inf>4</inf>ClO<inf>4</inf>, all Cd<sup>2+</sup> and Zn<sup>2+</sup> were successfully replaced. 15 g atoms of Cu<sup>+</sup> from the acetonitrile perchlorate complex were bound to the protein. Due to the absence of aromatic amino acid residues, thionein has unique ultraviolet and circular dichroism properties. The shoulder of the ultraviolet spectrum at 250 nm (A<inf>250</inf> x A<inf>280</inf><sup>-1</sup> = 23.9) was shifted to 275 nm (A<inf>250</inf> x A<inf>280</inf><sup>-1</sup> = 1.6). No significant absorption was detected in the visible region. The conformational changes of the protein moiety were much more visible in the circular dichroism spectra. The titration with Cu(CH<inf>3</inf>CN)<inf>2</inf><sup>+</sup> caused the appearence of three new Cotton effects: 257.5 nm (<sup>+</sup>), 350 nm (+) and 301 nm (-). The negative Cotton effect at 239 nm of the original metallothionein was completely levelled off. The binding strength of copper with thionein is extraordinarily high: it survives proton treatment up to pH 1.9. Displacement of the Cd<sup>2+</sup> by Cu<sup>+</sup> employing Cd thionein which was formed at pH 2.2, resulted in the same circular dichroism properties as observed for Cu thionein. D Penicillamine proved a suitable model for the metal free thionein, since redox reactions and polymerization of the sterically hindered thiol residue are known to be slow. The correlation of the circular dichroism properties of either copper complex using thionein or D penicillamine was surprisingly high. Circular dichroism measurements of Cu(I) D penicillamine revealed Cotton effects at 255 nm (+), 280 nm (+) and 355 nm (-). Upon examining the red violet mixed Cu(I) Cu(II) D penicillamine complex, Cotton bands in the visible region at 425 nm (-) and 495 nm (+) were seen. In many blue copper enzymes, the copper is assumed to be in the neighborhood of cysteine and aromatic amino acid residues, which are known to play an important role in the electron transfer. This is not the case in the Cu thionein, which would explain many different properties of this copper protein. It is very attractive to conclude that the sterically hindered SH group of D penicillamine reacts with excess copper in a specific way, similar to the Cu thionein. This phenomenon could explain the considerable success of D penicillamine in the treatment of Wilson's disease.",chicken;in vitro study;liver;liver cell;spectroscopy;theoretical study;cadmium;cadmium chloride;copper;copper complex;penicillamine;thioneine;zinc,"Rupp, H.;Voelter, W.;Weser, U.",1975,,,0,0,
3195,Penicillamine therapy: nine year follow up in two male siblings with Wilson's disease,,child;drug therapy;sibling;therapy;Wilson disease;penicillamine;pyridoxine,"Carnica, A.;Rennert, O.;Tiwary, C.",1975,,,0,0,
3196,Wilson's disease. Skin changes due to penicillamine treatment. [German],,adverse drug reaction;drug therapy;hyperkeratosis;oral drug administration;skin toxicity;therapy;Wilson disease;penicillamine,"Gebhart, W.",1975,,,0,0,
3197,Portal circulation in longstanding cases of parenchymal liver damage due to Wilson's disease and treated with D penicillamine. [German],,brain disease;clinical study;drug therapy;electroencephalography;esophagus varices;liver function;liver scintiscanning;major clinical study;oral drug administration;portal hypertension;portal vein blood flow;spleen scintiscanning;therapy;Wilson disease;penicillamine;radioisotope,"Seidlova, V.;Kuba, J.",1975,,,0,0,
3198,Wilson's disease (hepatolenticular degeneration). [German],"Wilson's disease is caused by a disturbance in the copper metabolism with deposition of copper in the liver and cornea and histological changes, especially in the putamen. The neurological symptoms correspond to a mixture of a Parkinson like rigor and intention tremor with cerebellar and mental changes. The disease is recessively hereditary. Treatment with D penicillamine yields good to very good results if diagnosis is early. Additional therapeutic trial of L dopa against the extrapyramidal symptoms appears to be justified.",cornea;diagnosis;liver cirrhosis;major clinical study;putamen;review;therapy;Wilson disease;levodopa;penicillamine,"Hopf, H. C.",1975,,,0,0,
3199,Wilson's disease. Clinical and laboratory manifestations in 40 patients,"The clinical and laboratory manifestations in 40 (16 male, 24 female) Chinese patients with Wilson's disease (WD) are described. The average age of onset of symptoms in the 31 symptomatic patients was 12.2 yr for females and 22.1 yr for males. Eight of 10 presenting with symptoms after the age of 15 were male. Eighteen died of their disease at an average age of 19.1 yr. Kayser Fleischer rings were present in 37 patients. Splenomegaly and hyperpigmentation of the shins were noted in half. Bleeding and easy bruising occurred in 17. Less frequent symptoms or signs included; edema, arthralgias, jaundice, palpable liver and ascites. Neurological symptoms were common. More than half of the patients had at least one of the following: poor coordination, psychological impairment, tremor, dysarthria, dysphagia, masked facies, disturbed gait, rigidity, dementia, dystonia, hypertonia and drooling. Pancytopenia was a frequent finding, correlating with splenomegaly. Hyperchloremia, hypokalemia and low serum carbon dioxide content associated with fixed alkaline pH of urine suggested renal tubular acidosis (RTA). Serum uric acid was reduced and uric acid clearance was increased in almost all patients. Hyper aminoaciduria occurred in most patients who had received less than 1 yr of penicillamine treatment. Elevated serum creatinine and BUN and reduced creatinine clearance were found. Fasting blood sugars were normal and glycosuria was not detected. Serum calcium was reduced and calcium clearance was increased. Serum inorganic phosphates were low in 60%, and phosphorus clearance was increased in 36%. Four patients had bony deformities. Prothrombin time was the most frequent abnormal liver function test. BSP retention was present in 75%, SGOT was elevated in 36%; SGPT in 14%. Serum proteins, albumin and transferrin was reduced in about 1/4 and complement in 3 of 16. IgG and IgM were occasionally elevated. Total serum bilirubin was increased in 1/3 and the direct fraction of bilirubin was elevated in 1/4. Urinary abnormalities often included; pH> 6.5, specific gravity of 1.015 or lower, microscopic hematuria and minimal proteinuria. The classical abnormalities of copper metabolism; hypoceruloplasminemia, hypocuprinemia, hypercuprinuria, and increased hepatic copper concentration, were almost always present. It is suggested that these tests and the results of liver biopsy and clinical and laboratory findings, including renal function tests, be utilized to separate the asymptomatic homozygote from the heterozygote for WD.",acid base balance;age;bleeding;diagnosis;dystonia;electrolyte blood level;etiology;hyperpigmentation;kayser fleischer ring;liver cirrhosis;liver function test;major clinical study;mental deficiency;methodology;mortality;neurologic disease;pancytopenia;prothrombin time;review;sex;skin;splenomegaly;therapy;Wilson disease;bromsulfophthalein;ceruloplasmin;copper;penicillamine,"Strickland, G. T.;Leu, M. L.",1975,,,0,0,
3200,Wilson's disease (hepatolenticular degeneration). [German],"In Wilson's disease there is a low caeruloplasmin level, as a result of which copper is carried loosely bound to albumin and is released to different tissues and some is excreted in urine. The cause is probably a genetic defect which allows an increase of copper absorption because of the caeruloplasmin deficiency. In the forefront of internal damage in this disease complex are cirrhosis of the liver and kidney damage. The multiple organ affection gives a multiplicity of clinical symptoms e.g. the hepato cerebral form, the abdominal or hepatic type and the pseudosclerosis or neurological type. Apart from these there are changes in coagulation and in bones and joints. The principal laboratory interest is in copper metabolism. In treatment D penicillamine is the drug of choice but side effects are to be reckoned with in a high percentage of cases.",diagnosis;liver cirrhosis;review;therapy;Wilson disease;ceruloplasmin;copper;penicillamine,"Perings, E.",1975,,,0,0,
3201,The effect of penicillamine therapy on the lesion of the liver in Wilson's cirrhosis. Clinical microscopic and electron microscopic study (Turkish). [Turkish],,child;electron microscopy;histology;liver;major clinical study;Wilson disease;penicillamine,"Ege, B.;Kilicturgay, K.;Karagol, U.;Imamoglu, A.",1974,,,0,0,
3202,Penicillamine (Dutch). [Dutch],,adverse drug reaction;agranulocytosis;anemia;anorexia;arthralgia;clinical study;cystinuria;double blind procedure;drug dose;drug interaction;drug therapy;drug toxicity;eosinophilia;erythema;fever;hematuria;joint;kidney;leukopenia;major clinical study;nausea;nephrotic syndrome;neuropathy;oral drug administration;pain;proteinuria;pruritus;rash;rheumatoid arthritis;stomatitis;therapy;thrombocytopenia;urticaria;vomiting;Wilson disease;acetylsalicylic acid;chloroquine;gold;hemoglobin;immunoglobulin;immunoglobulin G;immunoglobulin M;indometacin;naproxen;penicillamine;placebo;rheumatoid factor,Anonymous,1974,,,0,0,
3203,Wilson's disease. Analytical study in a boy of 13 years. The results of exploration of the family. [French],"A case of Wilson's disease is reported; a boy who presented with different aspects of the condition: ascitic cirrhosis and neurological signs. Investigation into the family history showed that the patient's mother had a marked diminution of ceruloplasmin. A younger brother showed a moderate diminution: about 16 mg/100 ml. It will be necessary to check the ceruloplasmin in this younger brother, and it is hoped to analyse the hepatic copper after liver biopsy. If it should be shown to be increased, cuprimine will be given. This treatment has been shown to be successful in a number of publications, especially when given in the infraclinical stage.",anemia;arthralgia;ascites;autopsy;blood clotting disorder;brain cortex;diagnosis;edema;eruption;fever;hepatosplenomegaly;in vitro study;internal medicine;jaundice;liver;liver cirrhosis;major clinical study;mammal;mitochondrion;nephrotic syndrome;ophthalmology;rigidity;skin;spleen;tremor;Wilson disease;ceruloplasmin;copper;immunoglobulin;penicillamine;pyridoxine,"Lahlou, B.;Benabadji, A.;Tazi, M.",1974,,,0,0,
3204,Excretion of copper in sweat of patients with Wilson's disease during sauna bathing,"Copper was measured by atomic absorption spectrometry in sweat samples obtained during sauna bathing (15 min at 93degree) from 7 patients (2 males and 5 females) with Wilson's disease (hepatolenticular degeneration). In one patient who was not being treated with penicillamine, the estimated excretion of copper in total body sweat during the sauna bath was 18 mug. In 6 patients who were receiving oral penicillamine (1 g per day), the estimated excretions of copper in total body sweat during the sauna bath averaged 106 mug, (range = 43 to 179). This study shows that sweating can be a significant route for the excretion of copper in patients with Wilson's disease who are being treated with penicillamine. Thermal induction of sweating by means of sauna bathing may possibly serve as a therapeutic adjunct to the customary treatment of Wilson's disease by means of low copper diet and penicillamine.",biochemistry;copper excretion;diagnosis;internal medicine;methodology;sweat;Wilson disease;copper;penicillamine,"Sunderman Jr, F. W.;Hohnadel, D. C.;Evenson, M. A.;Wannamaker, B. B.;Dahl, D. S.",1974,,,0,0,
3205,Lupus induced by D penicillamine during treatment of rheumatoid arthritis. Two cases and immunologic study during treatment. [French],"On the basis of 2 observations of lupus erythematosus induced by administration of D penicillamine in the course of treatment of rheumatoid arthritis, the authors provide a systematic study of the biological features of lupus during such therapy. The first observation involved a woman aged 45 yr with seronegative rheumatoid arthritis. In the 11th mth there was an episode of muscular pain with the appearance of LE cells and antinuclear antibodies. The clinical signs vanished when the treatment was stopped. The second case was a woman aged 53 with seropositive rheumatoid arthritis, in whom there was facial eruption and the appearance of antinuclear antibodies in the 11th mth. The eruption disappeared when the treatment was stopped but subsequent resumption of treatment resulted in the reappearance of the eruption and antinuclear antibodies. In the systematic study involving 25 patients (including the 2 described above), the authors found by the use of indirect immunofluorescence on liver sections that the antinuclear antibodies were initially absent in 15 patients. During treatment, 10 of these negative cases became positive, usually to a slight extent only. Of the 10 initially positive cases, 3 became negative during treatment and 3 significantly increased. With the aid of the latex agglutination test it was demonstrated that anti DPN antibodies remained absent in all 25 patients. The observations are comparable with those described in the literature on the treatment of Wilson's disease, or cystinuria. The absence of immunological anomalies before treatment in the two cases described indicates that the lupus was induced by the treatment of rheumatoid arthritis. The extent or frequency of occurrence of antinuclear antibodies in approximately half the cases during D penicillamine therapy of rheumatoid arthritis may be compared with results obtained with the use of procainamide or hydralazine. Lupus induced by D penicillamine appears to be quite rare even in cases of rheumatoid arthritis in which the antinuclear antibodies are positive. The presence of such antibodies does not appear to be sufficient to contraindicate the use of D penicillamine against rheumatoid arthritis.",adverse drug reaction;drug analysis;etiology;immunology;major clinical study;oral drug administration;pharmacology;rheumatoid arthritis;systemic lupus erythematosus;therapy;penicillamine,"Crouzet, J.;Camus, J. P.;Leca, A. P.;Guillien, P.;Lievre, J. A.",1974,,,0,0,
3206,Two cases of Wilson's disease detected in the subclinical stage. Result of early and prolonged penicillamine treatment. [French],"In this communication a report is given of two cases of Wilson's disease that were detected and treated at the infraclinical stage. The patients were two members of a single sibship: a boy who had been treated for 8 years and a half, and a girl who has been treated for 8 years, but neither of whom has so far developed any clinical sign of the disease. The detection of these 2 cases occurred on the occasion of the clinical and biological diagnosis in the same family of 2 cases of Wilson's disease in which both patients died: one with a neurological syndrome, and the other with a clinical picture of hepatic coma. Prolonged penicillamine did not cause any complications. (Journal received July 1975)",alanine aminotransferase blood level;aspartate aminotransferase blood level;copper excretion;copper urine level;drug therapy;major clinical study;oral drug administration;therapy;urine;Wilson disease;bilirubin;bromsulfophthalein;copper;penicillamine;prothrombin,"Hamza, B.;El Kamel, M.",1974,,,0,0,
3207,Neurological features of Wilson's disease. [French],"In addition to the typical form of Wilson's disease with rigidity and dyskinesia, it is important to consider this diagnosis when less common symptoms are present, such as fits and psychological disturbances. A Kayser Fleischer ring is always present as early as the first neurological signs, and this makes diagnosis simple. However, although penicillamine treatment has ameliorated the neurological prognosis considerably, its action on major hepatic lesions is less clear, and tolerance is not always perfect. Hence the importance of diagnosis in the presymptomatic stage, which can be done only by assessing the serum levels of ceruloplasmin in the sibs of patients, with measurement of copper levels in the tissues by liver biopsy in those with a low ceruloplasmin level.",anuria;dysarthria;dyskinesia;electroencephalography;epilepsy;kayser fleischer ring;oliguria;proteinuria;rigidity;thrombocytopenia;Wilson disease;ceruloplasmin;copper;penicillamine;pyridoxine,"Pepin, B.;Haguenau, M.",1974,,,0,0,
3208,The cure of chronic aggressive hepatitis by D Penicillamin (Slovene). [Slovene],"D penicillamine, which has already proved to be effective in the therapy of Wilson's disease, rheumatoid arthritis and scleroderma, is now being introduced into the area of chronic aggressive hepatitis (CAH). A nonspecific mesenchymal reaction with an accentuated collagen synthesis represents the basic event both in the collagenoses and in CAH via an indirect blockade of cysteine, D penicillamine obstructs collagen synthesis and consequential fibroplasia. The contraindications of such treatment, known so far, are renal insufficiency and disorders of the hematopoietic system. D penicillamine was given to 10 patients with CAH who had not responded to corticosteroid and immunosuppressive medication, in that the histologic picture of the liver had not improved. In all but 2 patients (all of them younger than 45 yr, their average age being 29.4 yr) there was a manifest subjective improvement and normalization of laboratory findings. Seven patients could be bioptically controlled. In 3 patients the histologic picture improved to such a degree as to indicate a practical clearing of the morbid process. In 2 patients the signs of aggressiveness disappeared, while one patient remained unchanged, and one displayed an even stronger aggressiveness in the histologic picture. In 3 patients unwanted side effects in the form of skin and mucous membrane changes were observed. A trial with D penicillamine seems justified, especially with AuAg positive subjects with CAH in whom corticosteroid or immunosuppressive treatment may be hazardous, or in whom such treatment has proved unsuccessful. Should changes in the oral mucosa appear, the treatment is immediately to be discontinued.",chronic active hepatitis;chronic hepatitis;clinical study;hematopoiesis;hepatitis;histology;immunosuppressive treatment;kidney failure;major clinical study;microscopy;therapy;collagen;corticosteroid;penicillamine,"Zaversnik, H.;Acko, M.",1974,,,0,0,
3209,Penicillamine in Huntington's chorea,"Huntington's chorea, a dominantly inherited disorder associated with loss of cells in the basal ganglia of the brain, was investigated for a possible abnormality in manganese metabolism. Manganese was measured in the urine after penicillamine and calcium edetate; there was no significant alteration in the excretion of this metal after either of these agents. Pencillamine was given in a therapeutic trial to 8 patients and appeared to produce a transient clinical improvement; but over a period of one yr it did not halt the natural progression of the disease.",age;basal ganglion;chorea;drug excretion;Huntington chorea;intravenous drug administration;oral drug administration;theoretical study;urine;Wilson disease;4 aminobutyric acid;acetylcholine;aromatic levo amino acid decarboxylase;catecholamine;copper;diethyldithiocarbamic acid;dimercaprol;dopamine;dopamine beta monooxygenase;edetate calcium;manganese;penicillamine;placebo,"Bird, E. D.;Pilling, J. B.;Heathfield, K. W. G.",1974,,,0,0,
3210,Psychologic investigation of Wilson's disease,"Twenty patients with Wilson's disease, who had been treated with D penicillamine and a low copper diet for various lengths of time, were examined with various psychologic tests. Compared with normal controls, these patients were significantly inferior on measures related to upper extremity motor speed and fine motor coordination.",diagnosis;diet;major clinical study;motor coordination;psychologic test;Wilson disease;copper;penicillamine,"Davis Jr, L. J.;Goldstein, N. P.",1974,,,0,0,
3211,Effects of penicillamine therapy and low copper diet on dysarthria in Wilson's disease (hepatolenticular degeneration),"For 10 patients with Wilson's disease, speech recordings were made prior to the institution of treatment with D penicillamine and a low copper diet and again after 3 year of treatment. The 20 samples, dubbed in random order onto a master tape, were rated on a number of speech characteristics by 3 judges. The improvement in the general neurologic status of these 10 patients after 3 years of treatment was mirrored by the improvement in speech. The evaluation of speech can be used as an effective monitor of improvement in the treatment of Wilson's disease.",clinical study;diet;dysarthria;feeding behavior;major clinical study;speech;therapy;Wilson disease;copper;penicillamine,"Berry, W. R.;Aronson, A. E.;Darley, F. L.;Goldstein, N. P.",1974,,,0,0,
3212,Symposium on copper metabolism and Wilson's disease,,brain cortex;brain injury;cerebellum;ceruloplasmin blood level;corpus striatum;diagnosis;epidemiology;genetics;liver cirrhosis;liver disease;nuclear medicine;review;therapy;Wilson disease;ceruloplasmin;copper;dimercaprol;penicillamine,"Goldstein, N. P.;Owen Jr, C. A.",1974,,,0,0,
3213,Wilson's disease. [French],"Wilson's disease is a rare genetically determined condition characterized by accumulation of copper in the body and in particular in the liver, brain and corneas. The onset, usually between the ages of 10 and 20 yr, is marked by neurological signs and symptoms combining dyskinesia with dystonia. Generally there is little or no evidence of liver involvement and a picture of cirrhosis is rare. Kayser Fleischer ring is a practically constant sign and pathognomonic of the disease. Chelation with D penicillamine is usually followed by regression of the neurological signs and symtoms of the disease. Its effect on hepatic changes is less certain. The drug is remarkably effective in preventing the development of clinical manifestations in asymptomatic disease, as discovered on systematic enquiry into the family tree and the 2 main biochemical abnormalities, namely a reduced level of circulating ceruloplasmin and raised liver copper.",cornea;diagnosis;dyskinesia;dystonia;genetics;kayser fleischer ring;liver;liver cirrhosis;plasma;therapy;urine;Wilson disease;ceruloplasmin;copper;penicillamine,"Sicot, C.",1974,,,0,0,
3214,Bicarbonate excretion in Wilson's disease (hepatolenticular degeneration),"Acid excretion and bicarbonate excretion in 13 patients with Wilson's disease, 11 of whom had been treated with D penicillamine were examined. Five patients had had serum bicarbonate levels less than 22 mEq/l before penicillamine treatment but only one had such a value at the time of these studies. Nine patients did not acidify their urine to pH 5.2 after ammonium chloride loading. Tm for bicarbonate was low after bicarbonate loading in only two patients although the threshold for bicarbonate excretion was apparently decreased in half the patients (that is, excretion greater than muEq/min at a plasma level less than 22 mEq/l). Mean bicarbonate excretion was high at normal plasma bicarbonate levels but was less than 3% of the filtered load in all but two patients. These data suggest that two patients had type II or proximal renal tubular acidosis (RTA) and an additional seven had a gradient defect or distal RTA. Bicarbonate wasting was minimal in most patients and could have been due either to direct tubular damage or indirectly to the gradient defect for hydrogen ion excretion.",bicarbonate blood level;bicarbonate urine level;ceruloplasmin blood level;clinical study;diuresis;feeding behavior;kidney;kidney tubule;kidney tubule acidosis;major clinical study;therapy;Wilson disease;ammonium chloride;copper;copper 67;penicillamine;radioisotope,"Wilson, D. M.;Goldstein, N. P.",1974,,,0,0,
3215,Long term body retention of radiocopper (<sup>67</sup>Cu) and the diagnosis of Wilson's disease,"Results of long term body retention studies using <sup>67</sup>Cu support previous <sup>64</sup>Cu data suggesting an increased copper turnover in the liver shortly after intravenous injection of radiocopper and a constant excretion rate thereafter, both phases being of pathophysiologic significance for copper kinetics. For separation of normals, Wilson's disease (WD) patients, and heterozygous carriers of the WD gene, results of body retention studies with carrier free <sup>67</sup>Cu were found to be inferior to earlier results obtained with <sup>64</sup>Cu of variable specific activity. Long term body retention studies and simultaneous determination of plasma incorporation using <sup>67</sup>Cu with carrier copper might yield better discrimination of homozygous WD patients and heterozygous WD carriers from the normal population.","article;clinical study;diagnosis;drug distribution;liver;major clinical study;plasma;therapy;Wilson disease;4h 1,2,4 triazolo[4,3 a][1,4]diazepine derivative;acetate cupric cu 64;copper;copper 64;copper 67;penicillamine;radioisotope;unclassified drug","Willvonseder, R.;Goldstein, N. P.;Tauxe, W. N.",1974,,,0,0,
3216,Trace metals in the central nervous system. State of research: successes and future prospects. [German],,brain;brain disease;central nervous system;cerebrospinal fluid;cytology;drug distribution;encephalitis;epilepsy;etiology;extrapyramidal syndrome;hippocampus;meningitis;neuroaxonal dystrophy;neurosis;oligophrenia;review;schizophrenia;Wilson disease;calcium;ceruloplasmin;copper;dimercaprol;dithizone;iron;lithium;magnesium;manganese;nickel;penicillamine;strontium;trace element;trace metal;zinc,"Prange, H.;Prange, C.",1974,,,0,0,
3217,A skin complication during treatment of Wilson's disease with D penicillamine. [French],,adverse drug reaction;copper blood level;drug therapy;electron microscopy;oral drug administration;plaque;skin;skin cyst;therapy;urine;Wilson disease;collagen;copper;elastin;penicillamine,"Texier, L.;Loiseau, P.;Henry, P.",1974,,,0,0,
3218,Wilson's disease: evolutionary and therapeutic evaluation in a case followed up long term. [French],,adverse drug reaction;blood;clinical study;drug therapy;drug toxicity;electroencephalography;extrapyramidal syndrome;histology;kidney;liver;liver cirrhosis;liver function test;major clinical study;microscopy;ophthalmoscopy;oral drug administration;pigmentation;therapy;tremor;Wilson disease;ceruloplasmin;copper;penicillamine,"Mouren, P.;Poinso, Y.;Soubeyrand, J.",1974,,,0,0,
3219,Serum immunoglobulin level in patients with Wilson's disease (Polish). [Polish],"The serum immunoglobulin levels were determined by Mancini's method of immunodiffusion in 15 cases of Wilson's disease, 12 cases of hepatic cirrhosis following virus hepatitis, and in 15 blood donors. The serum IgG level in the cases of Wilson's disease was 553.66 i.u. (SD=211.86); it was statistically significantly higher than in the cases of cirrhosis and in the blood donors. On the other hand, the levels of IgM and IgA in the cases of Wilson's disease resembled those in the blood donors but they were lower than in the cases of liver cirrhosis. The investigations failed to explain the reason why the IgG level rises. The role of penicillamine taken by the patients at the time of the investigations is discussed.",diagnosis;etiology;hepatitis;immunoglobulin blood level;liver cirrhosis;liver disease;major clinical study;serum;virus infection;Wilson disease;immunoglobulin;immunoglobulin A;immunoglobulin G;immunoglobulin M;penicillamine,"Czlonkowska, A.",1974,,,0,0,
3220,Hepatolenticular degeneration. Presentation of a case. [Spanish],"A case of hepatolenticular degeneration of the Westphal Sturempell type, treated with penicillamine is reported. The only clinical manifestation was pruritus and a facial eruption which did not require any other treatment.",amino acid urine level;basal ganglion;degeneration;diagnosis;eruption;face;kayser fleischer ring;liver cirrhosis;urine;Wilson disease;ceruloplasmin;copper;penicillamine,"Cabrer, B.;Vivancos, J.;Coll, J.",1974,,,0,0,
3221,Wilson disease: experience in prolonged treatment with penicillamin. [Spanish],,drug therapy;major clinical study;metabolism;oral drug administration;therapy;Wilson disease;copper;penicillamine,"Escartin Marin, P.;Garcia Plaza, A.;Chantar Barrios, C.",1974,,,0,0,
3222,Drugs for rare disease: whose responsibility?,,drug industry;drug research;drug therapy;therapy;tropical disease;Wilson disease;benzodiazepine derivative;penicillamine;trientine,Anonymous,1974,,,0,0,
3223,Points to note during D penicillamine therapy. [German],,adverse drug reaction;cystinuria;gastrointestinal symptom;intoxication;leukocyte;nephrotoxicity;neuropathy;proteinuria;rheumatoid arthritis;skin allergy;taste;therapy;thrombocyte;thrombocytopenia;Wilson disease;penicillamine;pyridoxine;vitamin,Anonymous,1974,,,0,0,
3224,Hemolytic anemia in Wilson's disease (Norwegian). [Norwegian],"In 1970 a 17 yr old female was admitted to hospital with severe hemolytic anemia requiring blood transfusions. The hemolysis stopped when corticosteroids were given. After the withdrawal of corticosteroids she had another attack of hemolysis. This time too corticosteroids seemed to stop the hemolysis. In addition to hemolytic anemia, she had minor changes in liver function tests and in liver histology. No obvious cause for the hemolytic anemia was discovered. Approximately 3 yr later, she was readmitted with a clinical picture compatible with the affection of the basal ganglia. Kayser Fleischer's ring was found in the cornea, the liver function was normal. The urine copper output was increased, ceruloplasmin decreased and the copper content in liver tissue was high. Therapy with potassium chloride and penicillamine was started. Despite increased urinary copper excretion and high dosage of penicillamine her neurological symptoms progressed. However, after 9 mth of treatment slight improvement occurred and the liver copper content had decreased considerably. Wilson's disease was also diagnosed in her 2 yr younger, asymptomatic brother.",blood transfusion;hemolytic anemia;liver;major clinical study;therapy;Wilson disease;ceruloplasmin;copper;corticosteroid;penicillamine;potassium chloride,"Ritland, S.",1974,,,0,0,
3225,The metabolism of collagen. [French],,chronic liver disease;diagnosis;histology;metabolism;Wilson disease;collagen;penicillamine,"Thomas, M.",1974,,,0,0,
3226,The nature of the course and rehabilitation in the clinical stage of Wilson's disease. [German],"The results of treatment and rehabilitation of 24 Wilson's disease patients (17 hepatocerebral and 7 cerebral cases) are reported. The maximum duration of treatment was 9 yr. Early symptoms occurred between 2 and 23 yr for the hepatocerebral form, and between 14 and 35 yr for the cerebral form of Wilson's disease, the former form being diagnosed after about one year and the latter form after about two years from the manifestation of clinical (neurological) symptoms. Optimum penicillamine doses, the administration of which ensures a negative copper balance, caused even the serious neurological symptoms to disappear within 2 to 3 yr in cases where the disease was not accompnied by athetosis and/or dystonia musculorum deformans (socalled extrapyramidal composite pictures). 80% of the patients have either part time or full time jobs.",catatonia;diagnosis;fever;leukopenia;major clinical study;petechia;prevention;pruritus;psychosis;rash;rehabilitation;therapy;Wilson disease;ceruloplasmin;copper;penicillamine,"Loessner, J.;Eichner, B.;Bachmann, H.",1974,,,0,0,
3227,Wilson's disease (hepatolenticular degeneration) and pregnancy. [French],"The authors report a case history of a woman suffering from Wilson's disease, who was treated with D. Penicillamine before and during pregnancy. The child, who was born at term, was normally formed and free of disease. A review of the literature suggested by this case history would appear to confirm that D. Penicillamine is not teratogenic in human beings. The importance of prophylaxis against the onward transmission from one generation to another of this affliction is emphasized.",diagnosis;fetus;newborn;placenta;pregnancy;prevention;therapy;Wilson disease;penicillamine,"Toulouse, R.;Poirier, P. Y.;De Villartay andKerisit, A. J.",1974,,,0,0,
3228,Hazards of soil and water,"The author discusses the biologic hazards involved in the natural processes where organic and inorganic substances are carried by water to the plant and food chains until they eventually reach man. Particular attention is paid to the trace substances, such as copper, zinc, sodium and chloride, and their relation to the occurrence of afflictions such as Wilson's disease and cystic fibrosis.",environmental health;intoxication;methodology;soil pollution;water pollution,"Pinsent, R. J. F. H.",1974,,,0,0,
3229,Penicillamine for systemic sclerosis?,"Experimental evidence suggests that penicillamine might be useful particularly in the skin lesions of active systemic sclerosis. There is a little clinical evidence that some subjective and objective improvement may occur, and as no other more effective drug is available, penicillamine may be worth trying. Toxic effects are lessened by using low doses, but even so the drug should be used only when the patient is under strict and regular supervision.",adverse drug reaction;bone marrow depression;drug therapy;gastrointestinal symptom;gastrointestinal tract;lead poisoning;nephritis;oral drug administration;proteinuria;rash;scleroderma;taste;taste disorder;therapy;thrombocytopenia;Wilson disease;copper;penicillamine,Anonymous,1974,,,0,0,
3230,Syndromes of the extrapyramidal motor system and their medical treatment. [German],The role of acetylcholine and dopamine as transmitter substances in basal ganglia is described after a short introduction into anatomy and physiology of the extrapyramidal motor system. Various clinical syndromes and recent advances in their medical treatment are discussed.,athetosis;chorea;drug therapy;etiology;extrapyramidal syndrome;extrapyramidal system;hyperkinesia;motor system;myoclonus;Parkinson disease;parkinsonism;therapy;Wilson disease;4 aminobutyric acid;acetylcholine;amantadine;atropine;baclofen;belladonna alkaloid;benzatropine mesilate;benzoctamine;biperiden;butyrophenone derivative;copper;decarboxylase inhibitor;diazepam;dopamine;levodopa;metixene;metoclopramide;neurotransmitter;penicillamine;phenglutarimide;phenothiazine;procyclidine;trihexyphenidyl,"Soyka, D.",1974,,,0,0,
3231,The pathogenesis and evolution of Wilson's disease,"Wilson's disease may be defined as an autosomal recessively inherited disorder characterized by excessive copper storage, particularly in the liver, kidneys, brain and cornea, leading eventually to liver disease, proximal renal tubular reabsorption abnormalities, basal ganglion disease, and the characteristic Kayser Fleischer corneal rings. The metabolic abnormality is most likely an abnormal processing of copper by the liver which results in decreased biliary copper excretion, and accumulation of copper in the body. The biochemical nature of the hepatic defect in copper metabolism is unknown, but removal of copper from the body by chelation therapy is followed by dramatic reversal of all of the manifestations of the disease. This response to chelation therapy may be taken as evidence that the clinical and pathologic manifestations of the disease are due to the damaging effects of excessive deposition of copper in the tissues. A concept of the disease is presented which explains the variability of the clinical manifestations as successive stages in the natural evolution of the disease. According to this concept, copper accumulates in the liver until a certain critical level is reached. Copper is then released into the blood and progressive accumulation of copper in the brain ensues. After the copper in the brain reaches a critical level, neurologic disease appears, and unless copper accumulation is reversed by chelation therapy, progressive neurologic disease terminates the illness.",brain;drug therapy;estrogen therapy;etiology;genetics;hemolytic anemia;liver cirrhosis;liver failure;pathogenesis;therapy;Wilson disease;copper;penicillamine;potassium sulfide;pyrromycinone;unclassified drug,"Cartwright, G. E.;Lee, G. R.",1974,,,0,0,
3232,A case of cerebellar hepato lenticular degeneration treated with Cuprenil. [Polish],"A case of hepatolenticular degeneration in a woman aged 36 yr is described. The clinical picture was dominated by cerebello extra pyramidal manifestations. The degree of disability precluded independent existence. Final diagnosis was based on the presence of Keyser Fleischer rings at the edge of the cornea and the values obtained for serum ceruloplasmin and urine copper excretion. Ceruloplasmin as determined by Ravin's method was 0.18 extinction units (normal range 0.313 - 0.420). Urine copper before the treatment was up to 850 mcg% in 24 hr (normal up to 100 mcg%). Serum copper as determined by the Cartwright method was 200 mcg% (normal range 80 - 140 mcg%). During treatment with Kuprenil (Polish brand of D penicillamine) 2.0 g daily, the urinary excretion of copper ranged from 15 to 25 mg in 24 hr. After 2 mth treatment with Kuprenil the patient's condition showed a definite improvement and the Keyser Fleischer rings diappeared.",cerebellum;cerebellum degeneration;clinical study;drug therapy;liver degeneration;major clinical study;therapy;Wilson disease;penicillamine,"Lasinski, T.;Stepniewicz, W.",1974,,,0,0,
3233,Tiopronin (alpha mercaptopropionylglycine) in Wilson's disease. [Portuguese],,drug administration;drug therapy;internal medicine;major clinical study;therapy;Wilson disease;copper;dimercaprol;edetic acid;mercaptopurine;penicillamine;tiopronin,"Freitas, A. A.;Machado Caetano, J. A.",1973,,,0,0,
3234,"The stages of hepatic lesions in hepato lenticular degeneration: early lesions, portal hypertension and cancerous degeneration. [French]",,ceruloplasmin blood level;copper liver level;electron microscopy;histology;liver biopsy;liver cancer;liver cirrhosis;major clinical study;metastasis;pediatrics;portal hypertension;splenorenal shunt;Wilson disease;copper;penicillamine;penicillin G,"Vachon, A.;Paliard, P.;Barthe, J.",1973,,,0,0,
3235,The treatment of genetic metabolic diseases. [Italian],,cystinosis;Fabry disease;galactosemia;hereditary fructose intolerance;inborn error of metabolism;kidney transplantation;lactose intolerance;lysosome;mucopolysaccharidosis;oxalosis;phenylketonuria;plasma transfusion;therapy;uricemia;Wilson disease;acid phosphatase;allopurinol;arylsulfatase;ascorbic acid;cyanocobalamin;magnesium hydroxide;penicillamine;prednisolone;pyridoxine,"Durand, P.",1973,,,0,0,
3236,Wilson's disease: modification by L Dopa,"A remarkable improvement of motor performance was observed in a 14 years old boy with Wilson's disease, after combining L Dopa to a copper chelating regimen.",child;diet;major clinical study;motor performance;movement (physiology);therapy;Wilson disease;copper;levodopa;penicillamine;trientine,"Gelmers, H. J.;Troost, J.;Willemse, J.",1973,,,0,0,
3237,Trace elements and skin pigmentation,"Of the 50 or more trace elements known to exist in the body, zinc offers the most interesting prospects in its relation with melanin. Hyperpigmented skin lesions have been reported in patients with abnormalities of trace element metabolism, such as Wilson's disease and hemochromatosis. Although high serum copper levels are found in a number of hyperpigmentary conditions, like xeroderma pigmentosum and melanosis accompanying pregnancy or the intake of oral contraceptives, many other conditions with hypercupremia are not associated with pigmentary changes. In a recent study of vitiligo there was no evidence of copper deficiency in either skin or serum, while serum zinc levels were significantly reduced. However, any speculation on the role of trace elements in vitiligo would have to take into account the structural defect which underlies the absence of melanin. Heavy metals can produce skin discolouration in a number of ways. Melanosis has long been associated with the excessive use of medicaments containing heavy metals like arsenic, bismuth, gold or silver. In these cases, there is an increase in melanin within the basal cell layer and in dermal melanophages. Hyperpigmentation resulting from the use of mercury in cosmetic creams is probably more common than assumed. The particles of the metal itself may contribute to the colour of skin and can often be demonstrated directly in sections. The use of EDTA in skin complications following gold therapy has been advocated by Bureau (1967), in view of the renewed interest shown by rheumatologists in prescribing this heavy metal. The authors' findings suggest that gold can be retained by skin for a considerable length of time following its administration, and such an approach may, therefore, be justified in patients with a diminished ability to excrete gold.",diagnosis;melanosis;methodology;review;skin pigmentation;vitiligo;xeroderma pigmentosum;copper;trace element;zinc,"Molokhia, M. M.;Portnoy, B.",1973,,,0,0,
3238,Pyrazinamide and renal urate excretion in patients with Wilson's disease,,drug comparison;drug excretion;oral drug administration;theoretical study;therapy;uric acid blood level;Wilson disease;amino acid;penicillamine;pyrazinamide,"Wilson, D. M.;Goldstein, N. P.",1973,,,0,0,
3239,Satisfactory results of use of a combination of penicillamine with levodopa or with amantadine hydrochloride in a case of Wilson's disease. [Italian],"A case of Wilson's disease diagnosed in a 12 yr old girl is presented, in which serious involvement of the central nervous system was expressed as an extrapyramidal symptomatology. Penicillamine was associated with levodopa for over 1 yr, and with amantadine hydrochloride for about 1 mth. Both associations gave satisfactory results especially the former. It is suggested that all cases of Wilson's disease accompanied by extrapyramidal symptoms should be treated by associating penicillamine with one of the wellknown antiparkinsonian drugs.",drug mixture;Wilson disease;amantadine;levodopa;penicillamine,"Berio, A.;Vento, R.;Di Stefano, A.",1973,,,0,0,
3240,Mucosal ulcers in a case of Wilson's disease under treatment with D penicillamine. [French],,adverse drug reaction;etiology;intramuscular drug administration;major clinical study;mouth ulcer;mucosa;therapy;ulcer;Wilson disease;penicillamine,"Rimbaud, P.;Mirouze, J.;Meynadier, J.;Mary, P.",1973,,,0,0,
3241,Pathophysiology of hepatolenticular degeneration (Wilson's disease). [German],,autosomal recessive inheritance;bile;brain;central nervous system;diagnosis;etiology;kidney;liver;major clinical study;metabolism;review;spleen;therapy;Wilson disease;ceruloplasmin;chiniofon;copper;dimercaprol;penicillamine;unclassified drug,"Willvonseder, R.",1973,,,0,0,
3242,Influence of penicillamine and of sodium maleate on the acute toxicity and on the distribution of copper in certain organs,"It has been established in the course of experiments with female albino rats that D penicillamine administered intramuscularly at doses of 20 to 100 mg/kg shows a slight and unreliable antidotal effect upon acute subcutaneous poisoning with copper sulphate and reduces to an insignificant degree (expressed as insignificant trend) the content of copper in the liver and in the kidneys after a single subcutaneous injection with a sublethal dose of copper sulphate. Sodium maleate, administered subcutaneously in doses of 50 to 400 mg/kg, reduces the content of copper in the liver and kidneys (significantly or as a trend). In the smaller doses of 50 and 100 mg/kg it does not change significantly the toxicity of copper sulphate, while at the higher doses of 200 and 400 mg/kg its effect is a distinct intensification of this toxicity. Sodium maleate, administered at what in itself is an ineffective dose of 25 mg/kg does not alter the copper decorporating effect of penicillamine and shows a trend at potentiating its antidotal effect. The paper discusses the difference in the effect of penicillamine upon hepatolenticular degeneration and upon acute copper poisoning.",drug distribution;drug intoxication;drug toxicity;intoxication;intramuscular drug administration;kidney;liver;pharmacokinetics;rat;subcutaneous drug administration;theoretical study;copper sulfate;maleate sodium;penicillamine;unclassified drug,"Stoychev, T.",1973,,,0,0,
3243,Hepatolenticular degeneration (Wilson's disease) and rickets in children,"Hepato lenticular degeneration in 4 Indian children presenting initially as renal rickets is described and salient clinical, biochemical, radiological and electroencephalographic features are discussed. Follow up of these patients showed response to therapy with chelating agents, vitamin D and oral potassium sulphide, satisfactory in so far as these patients showed sustained improvement and did not deteriorate further in neurological symptoms and signs and hepatic function. However, the bony change appeared to be a slow progressive one and no significant change occurred in patients already severely affected in this manner.",article;child;diagnosis;electroencephalography;major clinical study;methodology;oral drug administration;radiology;renal rickets;rickets;therapy;Wilson disease;bicarbonate;calcium chloride;chelating agent;colecalciferol;dimercaprol;penicillamine;potassium;potassium chloride;potassium sulfide;unclassified drug,"Joshua, G. E.",1973,,,0,0,
3244,The organic psycho syndrome in Wilson's disease. (Longterm follow up with psychologic testing in 4 patients during d penicillamine therapy). [German],"The organic pyscho syndrome, personality changes and deterioration of the neurological symptoms of untreated Wilson's disease are demonstrated. Improvement during d penicillamine longterm therapy is stressed. 4 patients were diagnosed in childhood and were followed up for 6-10 yr with repeated psychological testing and personal communications. Social adaptation and satisfactory job performance during treatment are underlined. Only the future of 1 patient remains doubtful; this patient, however, shows very severe signs of debility not caused by Wilson's disease. Finally, the importance of such long term follow up with particular consideration of the organic psychosyndrome is outlined. This should also be observed in other diseases.",article;drug administration;major clinical study;organic psychosyndrome;personality disorder;psychologic test;social adaptation;therapy;Wilson disease;levodopa;penicillamine;potassium sulfide;thioctic acid;unclassified drug,"Hayek, H. W.;Knoll, E.;Widhalm, S.",1973,,,0,0,
3245,Copper homeostasis in the mammalian system,"Copper has been recognized as an essential dietary component for over four decades. After the early observation that copper is necessary to promote hematopoiesis, a wide variety of biological processes were shown to depend on an adequate supply of dietary copper. In addition, several experiments have been directed toward elucidating the mechanisms that regulate the absorption, transport, storage, detoxification, and excretion of copper in the mammalian body. Although this article is intended as a review of the literature related to copper homeostasis, a brief discussion of the general subject of copper metabolism is included by way of introduction.",bile;erythrocyte;estrogen therapy;intestine absorption;kinky hair;major clinical study;normal human;review;theoretical study;toxicity;Wilson disease;adrenalin;albumin;amino acid;cadmium;ceruloplasmin;copper;copper 64;copper protein;copper sulfate;corticosteroid;corticosterone;corticotropin;growth hormone;molybdenum;silver;soybean protein;sulfide;thyroid hormone;thyroxine;zinc,"Evans, G. W.",1973,,,0,0,
3246,Diagnosis and treatment of Wilson's disease in the preclinical stage. [German],"For an effective long term therapy with penicillamine the homozygote Wilson gene carriers must be diagnosed in the preclinical or asymptomatic stage, i.e. within the first 10 yr or if possible before 6 yr of age. Only a biochemical diagnosis can be carried out in the preclinical stage. It is advantageous to evaluate the degree of ceruloplasmin and total copper in the serum and to verify the changed radio copper kinetics. This is the only reliable diagnosis even for patients in whom a liver puncture with quantitative chemical detection of the copper has been contra indicated. The procedure developed by Biesold and Gunther (evaluation of the incorporation rate of 64 Cu in ceruloplasmin) has been an efficient and preferable method and is also used for routine check ups. Six of the authors' patients in the asymptomatic stage were cured of all symptoms after 5 to 6 yr of penicillamine treatment.",article;copper blood level;diagnosis;drug blood level;hemolytic anemia;liver;major clinical study;pharmacokinetics;therapy;Wilson disease;antiparkinson agent;ceruloplasmin;copper;copper 64;copper 67;diazepam;penicillamine;phenytoin;potassium sulfide;pyridoxine;pyrromycinone;unclassified drug,"Lossner, J.;Bachmann, H.;Eichner, B.",1973,,,0,0,
3247,Metals: From privation to pollution,"Lead and mercury, like many other metals, present specific health hazards: lead, primarily due to ingestion of paint and plaster in slum housing; mercury, because of industrial discharges in inland waterways and in the form of fungicides. The environmental redistribution of such metals, stemming from activities of a growing population, constitutes a potential ecological threat, but one for which in most instances presently available data do not permit a credible assessment of either the form of biologic changes that might eventually appear or the time scale of their appearance. Acquisition of such data is an exceedingly complex task, requiring the collaboration of science, industry, and government, but is clearly a pressing obligation. The author presents an examination of the contaminating effects of lead and mercury and outlines the steps that will be needed for the development of better analytical methods. Among the proposals submitted in this paper are: First, that long term trends in the redistribution of environmental metals and their rate of buildup must be studied and projected while simultaneously investigating and identifying local problems of pollution. Second, the investigation of the effects of metals on biological systems must be expanded and an attempt must be made to develop more sensitive signals of toxicity. In particular, the study of the biological consequences of long term, low dose metal exposure must be promoted and matrices that reflect and permit evaluation of metal ion imbalance and related biological antagonisms must be developed. Third, in support of such efforts, researchers must strive for still better analytical approaches that are sensitive, rapid and accurate.",anemia;ataxia;blood;drug analysis;drug blood level;drug intoxication;dwarfism;encephalitis;geographic distribution;gonad;heart failure;hemochromatosis;intoxication;liver necrosis;nephritis;neuropathy;pollution;polycythemia;review;skeleton;spectrophotometry;statistics;Wilson disease;cadmium;calcium;chromium;cobalt;copper;cyanocobalamin;glucose;iron;lead;magnesium;manganese;metal;molybdenum;potassium;selenium;silver;zinc,"Ulmer, D. D.",1973,,,0,0,
3248,Longterm treatment of Wilson's disease with penicillamine and other chelating agents (Japanese). [Japanese],,copper urine level;drug urine level;liver function test;major clinical study;pediatrics;therapy;urine;Wilson disease;chelating agent;copper;dimercaprol;edetic acid;glutathione;glycine;glycine derivative;penicillamine;thiolactic acid;unclassified drug,"Fukuda, K.;Ishii, A.",1972,,,0,0,
3249,Treatment of Wilson disease with ammonium tetrathiomolybdate: iV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease,"DESIGNA randomized, double-blind, controlled, 2-arm study of 48 patients with the neurologic presentation of Wilson disease. Patients either received 500 mg of trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times per day with meals and 20 mg 3 times per day between meals for 8 weeks. All patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8 weeks, with neurologic and speech function assessed weekly; discharged taking 50 mg of zinc 3 times per day, and returned annually for follow-up.SETTINGA university hospital referral setting.PATIENTSPrimarily newly diagnosed patients with Wilson disease presenting with neurologic symptoms who had not been treated longer than 4 weeks with an anticopper drug.INTERVENTIONTreatment with either trientine plus zinc or tetrathiomolybdate plus zinc.MAIN OUTCOME MEASURESNeurologic function was assessed by semiquantitative neurologic and speech examinations. Drug adverse events were evaluated by blood cell counts and biochemical measures.RESULTSSix of 23 patients in the trientine arm and 1 of 25 patients in the tetrathiomolybdate arm underwent neurologic deterioration (P<.05). Three patients receiving tetrathiomolybdate had adverse effects of anemia and/or leukopenia, and 4 had further transaminase elevations. One patient receiving trientine had an adverse effect of anemia. Four patients receiving trientine died during follow-up, 3 having shown initial neurologic deterioration. Neurologic and speech recovery during a 3-year follow-up period were quite good.CONCLUSIONTetrathiomolybdate is a better choice than trientine for preserving neurologic function in patients who present with neurologic disease.OBJECTIVETo compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery.","Adolescent;Anemia [chemically induced] [physiopathology];Chelating Agents [administration & dosage] [adverse effects];Copper [antagonists & inhibitors] [metabolism];Dose-Response Relationship, Drug;Double-Blind Method;Drug Administration Schedule;Hepatolenticular Degeneration [drug therapy] [physiopathology];Length of Stay;Molybdenum [administration & dosage] [adverse effects];Serum Albumin [drug effects] [metabolism];Speech [drug effects] [physiology];Speech Disorders [drug therapy] [physiopathology];Treatment Outcome;Trientine [administration & dosage] [adverse effects];Zinc [therapeutic use];Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];abnormally high substrate concentration in blood/si [Side Effect];adult;aminotransferase blood level;anemia/si [Side Effect];article;blood cell count;clinical article;clinical trial;controlled clinical trial;controlled study;disease exacerbation/si [Side Effect];double blind procedure;drug safety;female;follow up;hospital patient;human;leukemia/si [Side Effect];leukopenia/si [Side Effect];male;neurologic disease/si [Side Effect];priority journal;randomized controlled trial;speech analysis;time series analysis;treatment duration;university hospital;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];copper;tetrathiomolybdate ammonium/ae [Adverse Drug Reaction];tetrathiomolybdate ammonium/ct [Clinical Trial];tetrathiomolybdate ammonium/cb [Drug Combination];tetrathiomolybdate ammonium/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];Sr-cf","Brewer, Gj;Askari, F;Lorincz, Mt;Carlson, M;Schilsky, M;Kluin, Kj;Hedera, P;Moretti, P;Fink, Jk;Tankanow, R;Dick, Rb;Sitterly, J",2006,,10.1001/archneur.63.4.521,1,1,2105
3250,Treatment of Wilson's disease with zinc: xIV. Studies of the effect of zinc on lymphocyte function,"Although administration of zinc to human subjects has been reported to interfere with lymphocyte function, this single report has never been confirmed or refuted. We have developed zinc as a lifelong therapy for patients with Wilson's disease. Interference with lymphocyte function occurring as a side effect of zinc therapy could produce serious problems in our patients. We evaluated lymphocyte mitogenic response and natural killer cell activity in patients with Wilson's disease treated for 5 years or longer with zinc, in comparison with normal controls, and found no differences. In a second study, we evaluated these same parameters in patients with Wilson's disease before and after 1 year of zinc therapy, and again found no significant differences. We have seen no indications of immune suppression or increased susceptibility to infections in our patients, who have now been treated with zinc for up to 15 years. We conclude that any side effects from compromised lymphocyte function caused by administration of zinc are not of concern to patients with Wilson's disease.","Copper [blood];Hepatolenticular Degeneration [blood] [drug therapy] [immunology];Killer Cells, Natural [drug effects] [immunology];Lymphocyte Activation [drug effects];Reference Values;Tumor Cells, Cultured;Zinc [blood] [therapeutic use];Female[checkword];Humans[checkword];Male[checkword]","Brewer, Gj;Johnson, V;Kaplan, J",1997,,,0,1,587
3251,"Hepatolenticular degeneration: the comparative effectiveness of d-penicillamine, potassium sulfide, and diethylditbiocarbamate as decoppering agents",,Adolescent;Clinical Trials as Topic;Copper;Hepatolenticular Degeneration [drug therapy];Penicillamine [therapeutic use];Sulfides [therapeutic use];Thiocarbamates [therapeutic use];Child[checkword];Female[checkword];Humans[checkword];Male[checkword],"Hsia, Ye;Combs, Jt;Hook, L;Brandt, Ik",1966,,,0,1,
3252,Wilson's disease in personal material--disturbances in hemostasis,"Genetically determined impairment of copper excretion from the liver into the bile in Wilson's disease (WD) cause that ""free copper"" is accumulated in toxic amounts not only in the liver, but also in other organs. In WD liver biopsy often could not be made because of serious disturbances in hemostasis. The aim of the study was: a) to demonstrate our 9 patients with various form of WD. b) to examine some blood clotting factors and compare the results with these obtained in other liver diseases. The diagnosis of Wilson's disease was made on the basis of disturbed copper metabolism. Among our 9 patients (8 women and 1 man, between 17-33 years old) we diagnosed: 3 patients with fulminant Wilson's disease with all day deep jaundice, hemolytic anemia, haemorrhagic diathesis and liver failure, died, 2 patients with active chronic hepatitis, hemolytic anemia and haemorrhagic diathesis, 2 patients with liver cirrhosis, haemorrhagic diathesis, Kayser-Fleisher ring, neuropsychiatric syndrome, 2 asymptomatic patients without haemorrhagic diathesis. The prothrombin index and the factors of prothrombin stem (II, V, VII, X) were lower than in other kinds of cirrhosis. After treatment with d-penicillamine the clothing factors returned near to the norm, similar as the biochemical and immunological results.",Adolescent;Blood Coagulation Disorders [etiology] [physiopathology];Hepatolenticular Degeneration [complications] [diagnosis] [physiopathology];Liver Diseases [complications] [physiopathology];Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword],"Jab?o?ska-Kaszewska, I;Dabrowska, E;Ozieb?owski, A",1995,,,0,0,
3253,Time-course of changes in plasma levels of trace elements after thrombolysis during the acute phase of myocardial infarction in humans,"It has been suggested that the injury induced by reperfusion of the ischemic myocardium could result, in part, from the cytotoxic effects of oxygen free radicals. Since various trace elements are involved in several of the reactions leading to free radical production, we have measured plasma levels of copper, zinc, selenium, and iron: 1. In 18 patients (mean age 60 yr old) subjected to thrombolytic therapy within 6 h after the onset of a myocardial infarction (G1); 2. In 16 patients with coronary artery disease, but without a history of a previous myocardial infarction (MI) (mean age 50 yr old, G2); and 3. In 50 healthy volunteers divided into two subgroups according to age (mean age 33 yr old, G3 and 55 yr old, G4). Plasma myosin levels were used to estimate quantitatively the extent of the infarcted mass. Plasma trace element levels were measured in blood samples following centrifugation and storage at -80 degrees C. The main results were as followed: In G1 patients who have been subjected to thrombolysis, an important release of myosin was measured in plasma, with a peak at D6 (1678 vs 95 microU/L at H0). In those G1 patients after MI: 1. A significant increase in plasma copper levels was observed from day 4 to day 10 postinfarction (x1.15 in reference to the baseline data at H0); 2. A decrease in plasma zinc levels was observed and was maximum 12 h after the onset of the thrombolytic treatment; 3. A decrease in selenium concentration was observed in G1, as well as in G2 patients, compared to the control groups (80% of G3 and G4 values); and 4. A significant decrease in plasma iron levels was observed in G1 (67.8% of G3 and G4 control values) and was significant from H0 to day 7 (p < 0.01). In conclusion, this study underlined the time-course evolution of plasma trace element levels in the followup of patients who have been subjected to thrombolysis following a MI and the potential prognostic implication of such variations.",Copper [blood];Coronary Disease [blood];Iron [blood];Myocardial Infarction [blood] [drug therapy];Myocardial Reperfusion;Reference Values;Selenium [blood];Thrombolytic Therapy;Time Factors;Trace Elements [blood];Zinc [blood];Adult[checkword];Humans[checkword];Middle Aged[checkword];Sr-vasc,"Pucheu, S;Coudray, C;Vanzetto, G;Favier, A;Machecourt, J;Leiris, J",1995,,10.1007/BF02790115,0,0,
3254,Role of vitamin E supplementation on serum levels of copper and zinc in hemolytic anemic patients with G6PD deficiency,"Vitamin E scavenges free radicals and may prevent destruction of RBC in Glucose6-phosphate dehydrogenase (G6PD) deficient hemolytic anemia, where changes in copper (Cu) and zinc (Zn) may act as additional contributory factors for hemolysis. In the present study changes in serum Cu and Zn and role of vitamin E supplementation on these changes were observed in hemolytic anemic patients with G6PD deficiency. This study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during July 2005-June 2006. For this, 102 subjects with age ranged 5-40 years of both sexes were included in the study. Among them 68 were G6PD deficient patients, of whom 34 were in supplemented group and 34 were non-supplemented group. The supplemented group received vitamin E for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children < or =12 years (4 times daily). Age and sex matched 34 apparently healthy subjects with normal G6PD level were taken to observe the base line data (healthy control) and also for comparison. All the G6PD deficient patients were selected from the Out Patient Department (OPD) of Hematology, BSMMU, Dhaka, and all the healthy subjects from personal contact. Blood G6PD level was done by spectrophotometric method and serum Cu, Zn levels by atomic absorption spectrophotometric method. To observe the availability of binding proteins serum total protein, albumin, globulin and A:G ratio were done by standard laboratory techniques. All parameters were measured on day 1 of their 1st visit and also on day 60 in deficient groups. Data analysis was done by appropriate statistical method. Serum Cu was significantly (p<0.001) higher but serum Zn, total protein, albumin, A/G ratio were significantly (p<0.001) lower in G6PD deficient groups in comparison to those of healthy control on day 1. After vitamin E supplementation, values of these parameters were comparable with those of healthy control in supplemented group in comparison to those of their pre-supplemented and non-supplemented groups both on day 1 and day 60. So, vitamin E supplementation has got its effective role in restoration of normal serum concentration of Cu and Zn in this group of patients.","Adolescent;Anemia, Hemolytic [blood] [etiology] [therapy];Copper [blood];Glycogen Storage Disease Type I [blood] [complications] [therapy];Vitamin E [therapeutic use];Vitamins [therapeutic use];Zinc [blood];Adult[checkword];Child[checkword];Child, Preschool[checkword];Female[checkword];Humans[checkword];Male[checkword];Young Adult[checkword]","Sultana, N;Begum, N;Akhter, S;Begum, S;Quraishi, Sb;Ferdousi, S;Ali, T",2008,,,0,0,
3255,Effect of intragastric pH on the absorption of oral zinc acetate and zinc oxide in young healthy volunteers,"METHODS: After a 9-hour fast, 10 healthy subjects (5 males and 5 females) were given a single oral dose of 50 mg of elemental zinc as the acetate or the oxide salt and under either high or low intragastric pH conditions. In all phases, a Heidelberg capsule pH detector-transmitter was used to continuously monitor intragastric pH. During the high pH phases, single oral doses of famotidine 40 mg oral suspension were administered before the zinc to raise the intragastric pH above 5. Intragastric pH < or = 3 was maintained in the low pH phases.RESULTS: The mean plasma zinc area under the curve for zinc acetate at low pH (AL), zinc acetate at high pH (AH), zinc oxide at low pH (OL), and zinc oxide at high pH (OH) were 524, 378, 364, and 66 micrograms x h/dL, respectively. The highest zinc plasma concentrations occurred with the acetate salt at a low intragastric pH, while the lowest plasma concentrations occurred with the oxide salt at a high intragastric pH. The importance of pH to the dissolution of these salts was verified by in vitro tests. Twenty-four-hour urinary zinc excretion was the highest for the AL phase and lowest for the OH phase.CONCLUSION: This study indicates that intragastric pH and salt solubility-dissolution are important in the oral absorption of zinc. Specifically, the oxide salt is not an appropriate zinc salt to use in those patients with elevated intragastric pH.BACKGROUND: Zinc is an important nutrient and is necessary to maintain a multitude of physiologic processes. Mineral supplements that provide physiologic doses of zinc may be used when dietary zinc is inadequate. Zinc is also used in pharmacologic doses to treat zinc deficiency and diseases such as Wilson's disease and acrodermatitis enteropathica. Although there are several zinc salts available, they are not equal in solubility, which is thought to be a key factor in zinc absorption. Moreover, the solubility of the salts is affected by pH, which may vary between pH 1 and 7 under various physiologic conditions in the stomach. The objectives of this 2-way 4-phase crossover study were to evaluate the effect of high (> or = 5) and low (< or = 3) intragastric pH on the absorption of zinc from the acetate and oxide salt in young healthy volunteers.","Absorption;Acetates [administration & dosage] [metabolism] [pharmacokinetics];Acetic Acid;Administration, Oral;Adolescent;Analysis of Variance;Circadian Rhythm [physiology];Cross-Over Studies;Dose-Response Relationship, Drug;Hydrogen-Ion Concentration;Stomach [metabolism];Zinc [pharmacokinetics] [urine];Zinc Oxide [administration & dosage] [metabolism] [pharmacokinetics];Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-uppergi","Henderson, Lm;Brewer, Gj;Dressman, Jb;Swidan, Sz;DuRoss, Dj;Adair, Ch;Barnett, Jl;Berardi, Rr",1995,,10.1177/0148607195019005393,0,0,
3256,Tetrathiomolybdate versus trientine in the initial treatment of neurologic Wilson's disease,"Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeks* Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05). One patient on trientine had an adverse event while 7 on TM had adverse events. All adverse events were mild. Four patients in the trientine arm died during follow-up, 3 having shown initial neurologic deterioration, 2 patients in the TM arm died. In those patients who did not deteriorate or die, neurologic and speech recovery over 3 years was good. Interpretation: TM is a superior choice to trientine for the initial therapy of neurologic Wilson's disease. © 2008 Cambridge University Press.",alanine aminotransferase blood level;anemia/si [Side Effect];article;aspartate aminotransferase blood level;clinical article;clinical trial;controlled clinical trial;controlled study;copper blood level;disease exacerbation;double blind procedure;drug choice;drug safety;drug tolerability;fatality;follow up;hospital patient;human;laboratory test;leukopenia/si [Side Effect];maintenance therapy;neurologic examination;priority journal;quantitative analysis;randomized controlled trial;scoring system;side effect/si [Side Effect];speech and language assessment;Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/ae [Adverse Drug Reaction];tetrathiomolybdic acid/ct [Clinical Trial];tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/cm [Drug Comparison];tetrathiomolybdic acid/dt [Drug Therapy];trientine/ae [Adverse Drug Reaction];trientine/ct [Clinical Trial];trientine/cb [Drug Combination];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc/ct [Clinical Trial];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];Sr-cf,"Brewer, Gj;Askari, F;Lorincz, Mt;Carlson, M;Schilsky, M;Kluin, Kj;Hedera, P;Moretti, P;Fink, Jk;Tankanow, R;Dick, Rb;Sitterly, J",2008,,10.1017/S1748232107000043,1,1,1984
3257,Zinc therapy for wilson's disease and alzheimer's disease,"Zinc is effective in all phases of Wilson's disease treatment and is the treatment of choice for maintenance therapy. It acts by blocking copper absorption at the intestinal level, and lacks the side effects of the other two anticopper drugs. Zinc is approved in the US, Europe, and Japan for Wilson's disease maintenance therapy. We will discuss appropriate dosing, monitoring and follow-up of zinc treated Wilson's disease patients. Because we discovered Alzheimer's disease (AD) patients were zinc deficient, and zinc is so important for neuronal functioning, we did a double blind clinical trial of a new once a day, gastroretentive, 150 mg zinc tablet developed by Adeona Pharmaceuticals, for 6 months in AD patients. Zinc treated patients over age 70 had statistically significant better scores than the placebo group in two cognition scoring systems (ADAS-Cog, p= 0.037 and CDR-SOB, p= 0.03), indicating zinc therapy has efficacy in older patients with AD.",therapy;Wilson disease;Alzheimer disease;human;patient;maintenance therapy;follow up;monitoring;absorption;cognition;scoring system;Japan;tablet;double blind procedure;Europe;side effect;zinc;placebo;copper,"Brewer, Gj",2011,,,0,0,1733
3258,"An ongoing phase 2, multi-center, open-label, study of WTX101 in newly diagnosed wilson disease patients","Background and aims WTX101 (bis-choline tetrathiomolybdate) is an investigational drug with a novel copper binding mechanism, which is tested in an ongoing prospective study to evaluate the safety and efficacy in newly diagnosed Wilson Disease (WD) patients. Methods Patients with a confirmed diagnosis of WD aged > 18 years and naive to treatment or treated for < 2 years with chelation or zinc therapy initially received 15 or 30 mg WTX101 QD, and after 6 weeks, dosage was guided by laboratory and clinical criteria. Regular assessments included safety, status of liver disease, neurological status using the Unified Wilson Disease Rating Scale (UWDRS), and parameters of copper metabolism. Results Twenty-eight patients have been enrolled in the study. On trial entry, most patients were untreated or treated for < 28 days with WD therapy, only 5/28 treated > 90 days. Baseline average non-ceruloplasmin copper (NCC) was elevated (3.5mM), 25/28 had neurological manifestations at baseline and average UWDRS part III was 22. Modified Nazer score ranged from 1 to 5. Adverse events (AEs) included reversible elevated liver tests (n=5, of which 3 were related to per protocol dose escalation) and neutropenia (n=2). After the initiation dose was reduced from 60 mg daily to 15-30 mg QD and dose escalation limited to 60 mg QD, WTX101 was well tolerated with few AEs. Hepatic status (ALT, INR and bilirubin) and the modified Nazer score improved or remained stable in all patients. NCC (adjusted for molybdenum) decreased over time on treatment. Other Cu measurements (exchangeable Cu, total serum Cu, 24-hour urinary Cu excretion) indicate a similar de-coppering pattern. The UWDRS part III scores largely improved in patients with neurological manifestations, or was stable in those without. Daily activity status (UWDRS part II) showed similar improvement. Summary WTX101 appears safe and well tolerated as initial therapy in patients with WD. Improvements in hepatic and neurologic disease, Cu metabolism and daily activity status over time was observed with WTX101 treatment. Further data are being accrued. Conclusion Further clinical evaluation of WTX101 is warranted to establish its safety and efficacy for the initial treatment of WD. The potential for once daily dosing will increase patient convenience and treatment adherence.",adverse drug reaction;chelation;clinical evaluation;clinical trial;controlled clinical trial;controlled study;copper metabolism;daily life activity;diagnosis;excretion;human;human tissue;international normalized ratio;liver disease;major clinical study;multicenter study;neurologic disease;neutropenia;open study;rating scale;safety;side effect;Wilson disease;bilirubin;molybdenum;zinc,"Schilsky, Ml;Askari, Fk;Ferenci, P;Ala, A;Czlonkowska, A;Nicholl, Dj;Bronstein, J;Bega, D;Weiss, Kh",2016,,,0,0,1136
3259,The promise of copper lowering therapy with tetrathiomolybdate in the cure of advanced previously incurable cancer and treatment of inflammatory diseases,"Tetrathiomolybdate (TM) complexes copper with protein in a strong tripartite complex. This complex with food protein is excreted in the stool causing a negative copper balance. In the blood this complex, TM, free copper, and albumin, renders free copper unavailable and nontoxic. TM, developed for Wilson's disease, is very effective for the neurologic presentation, for which no other drug is optimal. Lowering copper to intermediate levels with TM, levels high enough to avoid clinical deficiency, inhibits many cytokines, such as those promoting fibrotic, inflammatory, autoimmune diseases, and cancer. TM is efficacious in mouse models of pulmonary fibrosis and cirrhosis, inhibiting transforming growth factor beta (TGFbeta) and tumor necrosis factor alpha (TNFalpha). TM is efficacious in mouse models of inflammatory disease involving liver and heart, and four mouse models of immune modulated disease. In the human, TM reached both primary endpoints in a one year randomized controlled trial in primary biliary cirrhosis, an autoimmune attack on bile ducts. TM has great promise in the disease areas of fibrosis,inflammation, and autoimmunity. Wherever steroids are useful, TM will be better and safer. Most excitingly, recent developments show that TM can cure advanced, previously incurable, metastatic cancer. Tumor growth requires angiogenesis (Folkman). Many angiogenic promoters are copper dependent, particularly those active at the micrometastatic cancer level. MAJOR CLUE: TM COMPLETELY INHIBITED CANCER GROWTH IN THE HER/2neu MOUSE GENETIC MAMMARY CANCER MODEL. Micro clusters of cancer cells, still there after a year of TM therapy, couldn't grow because of a lack of angiogenesis, while all controls had large cancers. Human trials ignored this clue, and tried TM only only against advanced cancers. These can recruit many promoters, many not copper dependent, and only modest effects in these trials led to little interest. Now, two US groups are curing metastatic cancer with TM by harking back to the mouse clue. One group requires conventional suppression to no evidence of disease (NED) , although the disease is considered incurable because of micrometastases. After three years of TM the cancer is cured, with 10 different advanced metastatic, heretofore incurable cancers. The second group uses TM from the beginning, and conventional therapy plus certain therapies aimed at cancer metabolic vulnerabilities, curing many patients with different metastatic cancers. We have begun a randomized controlled trial of TM in micrometastatic osteosarcoma in dogs. It appears TM can cure many previously hopeless case of cancer.",therapy;neoplasm;inflammatory disease;human;mouse;mouse model;metastasis;angiogenesis;randomized controlled trial;promoter region;copper metabolism;cancer cell;lung fibrosis;tumor growth;liver cirrhosis;micrometastasis;blood;autoimmunity;inflammation;bile duct;primary biliary cirrhosis;autoimmune disease;protein intake;fibrosis;heart;liver;advanced cancer;patient;osteosarcoma;dog;Wilson disease;tetrathiomolybdic acid;copper;transforming growth factor beta;protein;albumin;steroid;cytokine;tumor necrosis factor alpha,"Brewer, Gj",2013,,,0,0,1531
3260,Zinc monotherapy for young children with asymptomatic wilson disease: multicenter study in japan,"Background and Aims: AASLD and EASL guidelines recommend zinc monotherapy as a treatment for asymptmoatic patients with Wilson disease (WD). However, there are a few reports of zinc monotherapy for young children with asymptomatic WD. Here, we aimed at evaluating long-term efficacy and safety of zinc monotherapy for young children, under 10 years old, with asymptomatic WD in Japanese pediatric centers and establishing appropriate benchmarks of maintenance therapy. Methods: We performed a retro- and prospective study to examine 21 children (median age 6 years, range 1-9) who satisfied diagnostic criteria for WD and were treated solely with zinc acetate prior to symptom onset at 10 participating pediatric centers in Japan. No additional WD sequelas, such as jaundice, hepatomegaly, or neurologic abnormalities were noted. We monitored serum AST and ALT, nonceruloplasmin serum copper, and 24-hour urinary copper for 1-7 years after initiation of zinc monotherapy. We performed abdominal ultrasonograpy and evaluated clinical WD manifestations, drug compliance, and adverse effects of zinc. The prescribed dosage of zinc acetate for patient < 5 years was 25 mg twice daily; for those children 6 years or older, the dose was 25 mg 3 times daily. We increased the dosage of zinc if the patients had AST/ALT > 50-70 U/L, and decreased it if they had adverse effects of zinc such as iron-deficiency anemia or pancytopenia. Results: At time of diagnosis, AST/ALT and 24-hour urinary copper were 148+/-118/234+/-151 U/L and 124+/-54 mug/day (5.8+/-2.9 mug/kg/day), respectively. All patients continued to take zinc without any evidence of zinc toxicity. None of our 21 patients became clinically symptomatic. AST/ALT significantly decreased to 54+/-30/77+/-49 U/L (P<0.001) at 1 month after initiation of treatment and was mostly maintained under 50 U/L for 1-7 years (AST/ALT: 33+/-7/38+/-17 and 29+/-5/34+/-6 U/L at 1 and 7 years after initiation of treatment, respectively). Twenty four-hour urinary copper significantly decreased to 49+/-21 mug/day (2.2+/-1.1 mug/kg/day; P<0.001) at 6 months after initiation of treatment and was mostly maintained under 75 mug/day and between 1 and 3 mug/kg/day for the remainder of the study (2.2+/-0.6 and 1.5+/-0.2 mug/kg/day at 1 and 7 years after initiation of treatment, respectively). Conclusions: Long-term zinc monotherapy for young children with asymptomatic WD proved highly effective and safe. A reasonable goal in treating young children with asymptomatic WD using zinc appears to be maintaining both AST/ALT under 50 U/L and 24-hour urinary copper excretion between 1 and 3 mug/kg/day (and under 75 mug/day).",adverse drug reaction;child;clinical article;clinical trial;comparative effectiveness;congenital malformation;controlled clinical trial;controlled study;copper blood level;diagnosis;drug therapy;excretion;hepatomegaly;human;human tissue;iron deficiency anemia;Japan;jaundice;maintenance therapy;medication compliance;monotherapy;multicenter study;nervous system;pancytopenia;pediatric hospital;pharmacokinetics;preschool child;prospective study;safety;school child;side effect;symptom;toxicity;Wilson disease;zinc;zinc acetate,"Mizuochi, T;Eda, K;Takaki, Y;Iwama, I;Araki, M;Inui, A;Hara, S;Kumagai, H;Hagiwara, S-I;Murayama, K;Murakami, J;Kodama, H",2016,,,0,0,1132
3261,Renal functional and structural integrity in infants with iron deficiency anemia: relation to oxidative stress and response to iron therapy,"Background: Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. The aim of our study was to evaluate and compare renal functional and structural integrity in 50 infants with IDA and 50 healthy controls and to assess the relation between IDA and oxidative stress and response to iron therapy. Methods: This was a prospective study in which peripheral blood samples were collected from all study subjects and the following laboratory investigations performed: serum iron profile, urinary microalbumin, urinary leucine aminopeptidase (LAP), fractional excretion of sodium (FeNa), serum total antioxidant capacity (TAC), serum malondialdehyde (MDA), serum and urinary trace elements (iron, copper, zinc, calcium and magnesium). All patients received oral iron therapy and were followed-up for 3 months. Results: The levels of baseline urinary markers were higher among the patients with IDA than among the controls (p < 0.05). Patients had a lower pre-therapy TAC and lower serum zinc and magnesium levels than controls as well as higher MDA and serum copper levels (p < 0.05). MDA level was positively correlated to microalbumin and LAP level (p < 0.05). Urinary LAP concentration was positively correlated to urinary trace element concentrations (p < 0.05). A significant decrease in microalbumin, LAP, FeNa, and urinary trace elements was observed post-iron therapy while hemoglobin and ferritin levels were increased (p < 0.05). Conclusion: Among the study subjects, IDA had an adverse influence on renal functional and structural integrity which could be reversed with iron therapy. Oxidative stress played an important role in the pathogenesis of renal injury in IDA. Copyright © 2015, IPNA.",article;calcium urine level;clinical article;controlled clinical trial;controlled study;copper blood level;creatinine blood level;female;ferritin blood level;follow up;human;infant;infant disease/dt [Drug Therapy];infant disease/dt [Drug Therapy];iron blood level;iron deficiency anemia/dt [Drug Therapy];iron deficiency anemia/dt [Drug Therapy];iron storage;iron therapy;kidney function;kidney structure;male;mean corpuscular hemoglobin;oxidative stress;priority journal;prospective study;sodium excretion;zinc blood level;calcium/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatinine/ec [Endogenous Compound];cytosol aminopeptidase/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];iron/ec [Endogenous Compound];iron derivative/dt [Drug Therapy];magnesium/ec [Endogenous Compound];malonaldehyde/ec [Endogenous Compound];sodium/ec [Endogenous Compound];zinc/ec [Endogenous Compound];blood;blood sampling;excretion;infant;iron deficiency anemia;kidney injury;laboratory;nutritional deficiency;pathogenesis;patient;serum;therapy;antioxidant;calcium;copper;cytosol aminopeptidase;ferritin;hemoglobin;iron;magnesium;malonaldehyde;marker;sodium;trace element;zinc,"El-Shimi, Ms;El-Farrash, Ra;Ismail, Ea;El-Safty, A;Nada, As;El-Gamel, Oa;Salem, Ym;Shoukry, Sm",2015,,10.1007/s00467-015-3122-6,0,0,
3262,Treatment of Wilson's disease with tetrathiomolybdate: v. Control of free copper by tetrathiomolybdate and a comparison with trientine,,Sr-liver,"Brewer, Gj;Askari, F;Dick, Rb;Sitterly, J;Fink, Jk;Carlson, M",2009,,,0,0,
3263,Comparison of long lasting therapeutic effects between succimer and penicillamine on hepatolenticular degeneration,"AIM:To compare the long-term effect of succimer (Suc) with that of penicillamine (Pen) in treating hepatolenticular degeneration (HLD).METHODS:One hundred and twenty patients with HLD were divided into 2 groups. Group A (n =60) received Suc 750mg,po.bid.Group B (n =60) received Pen 250mg, po. qid. The period of maintenance treatment varied from 6 months to 3 years, averaging 1.5 years. Symptoms and therapeutic effects were evaluated by modified Goldstein scale.RESULTS:The total effectiveness of group A in two different periods of treatment were 80% and 85% respectively, higher than those of group B (58% and 59% respectively)(P < 0.05). Suc also had obvious curative effects for the patients who failed in the use of Pen. There were fewer side effect in group A than in group B (P < 0.05). Suc and Pen could increase urinary copper excretion effectively and continually.CONCLUSION:Suc is more effective and safer than Pen. Clinically, it can replace Pen as first-choice drug for long-term maintenance therapy of HLD.",,"Ren, M. S.;Zhang, Z.;Wu, J. X.;Li, F.;Xue, B. C.;Yang, R. M.",1998,Dec,,1,1,
3264,Hepatic features of Wilson disease,"In Wilson disease (WD) defective AT7B function leads to biliary copper excretion and pathologic copper accumulation, particularly in liver and brain, where it induces cellular damage. Liver disease most often precedes neurologic or psychiatric manifestations. In most patients with neurologic or psychiatric symptoms there is some degree of liver disease at the time of disease presentation. Hepatic manifestations of WD can be extremely variable. Patients with clinically asymptomatic WD are often found by family screening or identified on routine laboratory testing. Others may have a clinical picture of chronic active hepatitis or of end-stage liver disease with cirrhosis. A minority present with acute liver failure, often on the background of advanced fibrosis. Complications from liver disease may be related to portal hypertension and concomitant liver disease may accelerate the course of liver disease. Liver cancer may occur in patients with WD, most commonly when cirrhosis and inflammation are present. The prognosis of patients with WD is excellent, especially for those without cirrhosis at the time of diagnosis, but requires timely initiation of appropriate therapy specific for WD and for the patient's liver disease independent of WD.",Brain/metabolism;Copper/metabolism;Copper-transporting ATPases/genetics;Hepatolenticular Degeneration/*complications/diagnosis/metabolism/psychology;Humans;Liver/metabolism/pathology;Liver Diseases/complications/pathology;Prognosis;Wilson disease;copper;liver disease;liver failure,"Boga, S.;Ala, A.;Schilsky, M. L.",2017,,10.1016/b978-0-444-63625-6.00009-4,0,0,
3265,A comparison of results of empirical studies of supplementary search techniques and recommendations in review methodology handbooks: a methodological review,"BACKGROUND: The purpose and contribution of supplementary search methods in systematic reviews is increasingly acknowledged. Numerous studies have demonstrated their potential in identifying studies or study data that would have been missed by bibliographic database searching alone. What is less certain is how supplementary search methods actually work, how they are applied, and the consequent advantages, disadvantages and resource implications of each search method. The aim of this study is to compare current practice in using supplementary search methods with methodological guidance. METHODS: Four methodological handbooks in informing systematic review practice in the UK were read and audited to establish current methodological guidance. Studies evaluating the use of supplementary search methods were identified by searching five bibliographic databases. Studies were included if they (1) reported practical application of a supplementary search method (descriptive) or (2) examined the utility of a supplementary search method (analytical) or (3) identified/explored factors that impact on the utility of a supplementary method, when applied in practice. RESULTS: Thirty-five studies were included in this review in addition to the four methodological handbooks. Studies were published between 1989 and 2016, and dates of publication of the handbooks ranged from 1994 to 2014. Five supplementary search methods were reviewed: contacting study authors, citation chasing, handsearching, searching trial registers and web searching. CONCLUSIONS: There is reasonable consistency between recommended best practice (handbooks) and current practice (methodological studies) as it relates to the application of supplementary search methods. The methodological studies provide useful information on the effectiveness of the supplementary search methods, often seeking to evaluate aspects of the method to improve effectiveness or efficiency. In this way, the studies advance the understanding of the supplementary search methods. Further research is required, however, so that a rational choice can be made about which supplementary search strategies should be used, and when.",Author contact;Citation searching;Handbooks;Handsearching;Information science;Supplementary searching;Systematic reviews;Trial searching;Web searching,"Cooper, C.;Booth, A.;Britten, N.;Garside, R.",2017,Nov 28,10.1186/s13643-017-0625-1,0,0,
3266,Wilson disease: neurologic features,"Wilson disease (WD) is a neurodegenerative disorder, which presents as a spectrum of neurologic manifestations that includes tremor, bradykinesia, rigidity, dystonia, chorea, dysarthria, and dysphagia, together with a combination of neurologic symptoms that can easily lead to misdiagnosis. An early diagnosis of WD, and appropriate anticopper treatment, usually leads to a marked improvement in patient health. Conversely, delayed diagnosis can result in persistent pathology, which, left untreated, can ultimately prove lethal. The aim of this chapter is to present a detailed description of the neurologic features of WD, including their evaluation, together with relevant ophthalmologic examinations, brain neuroimaging, and other laboratory measurements that show the extent of the involvement of the nervous system.",Brain/diagnostic imaging;Hepatolenticular Degeneration/classification/*complications/diagnostic imaging;Humans;Nervous System Diseases/classification/diagnostic imaging/*etiology;Kayser-Fleischer ring;Wilson disease;dystonia;neuroimaging;neurologic scales;parkinsonism;tremor,"Czlonkowska, A.;Litwin, T.;Chabik, G.",2017,,10.1016/b978-0-444-63625-6.00010-0,0,0,
3267,Clarifying the distinction between case series and cohort studies in systematic reviews of comparative studies: potential impact on body of evidence and workload,"Distinguishing cohort studies from case series is difficult.We propose a conceptualization of cohort studies in systematic reviews of comparative studies. The main aim of this conceptualization is to clarify the distinction between cohort studies and case series. We discuss the potential impact of the proposed conceptualization on the body of evidence and workload.All studies with exposure-based sampling gather multiple exposures (with at least two different exposures or levels of exposure) and enable calculation of relative risks that should be considered cohort studies in systematic reviews, including non-randomized studies. The term ""enables/can"" means that a predefined analytic comparison is not a prerequisite (i.e., the absolute risks per group and/or a risk ratio are provided). Instead, all studies for which sufficient data are available for reanalysis to compare different exposures (e.g., sufficient data in the publication) are classified as cohort studies.There are possibly large numbers of studies without a comparison for the exposure of interest but that do provide the necessary data to calculate effect measures for a comparison. Consequently, more studies could be included in a systematic review. Therefore, on the one hand, the outlined approach can increase the confidence in effect estimates and the strengths of conclusions. On the other hand, the workload would increase (e.g., additional data extraction and risk of bias assessment, as well as reanalyses).",*Cohort Studies;Evidence-Based Medicine;Humans;Outcome Assessment (Health Care)/methods;*Research Design;*Review Literature as Topic,"Mathes, T.;Pieper, D.",2017,Jul 17,10.1186/s12874-017-0391-8,0,0,
3268,The Yusuf-Peto method was not a robust method for meta-analyses of rare events data from antidepressant trials,"ObjectivesThe aim of the study was to identify the validity of effect estimates for serious rare adverse events in clinical study reports of antidepressants trials, across different meta-analysis methods.",,"Sharma, Tarang;Gøtzsche, Peter C.;Kuss, Oliver",2017,,10.1016/j.jclinepi.2017.07.006,0,0,
3269,Wilson's disease: A review for the general pediatrician,"Wilson's disease, also known as hepatolenticular degeneration, is an autosomal recessive genetic disorder due to a mutation of the ATP7B gene resulting in impaired hepatic copper excretion and copper accumulation in various tissues. It is associated with the classic triad of cirrhosis, neurological manifestations, and the ocular finding of Kayser-Fleischer rings; however, the clinical presentation can vary greatly from incidental findings of abnormal liver enzymes to acute liver failure necessitating liver transplant. Pediatric patients may present with subtle findings including asymptomatic hepatomegaly, transaminitis, changes in behavior, movement disorders, or school failure. The general pediatrician may be the first to recognize these symptoms and should consider Wilson's disease in their differential diagnosis. Wilson's disease can be managed with lifelong chelation or zinc therapy in patients who present early in the disease; therefore, pediatricians should have a low threshold for referral to a pediatric hepatolo-gist for further evaluation when it is suspected. Copyright © SLACK Incorporated.",academic failure;acute liver failure;article;chelation;child;differential diagnosis;drug therapy;excretion;eye;gene mutation;hepatomegaly;human;hypertransaminasemia;incidental finding;liver cirrhosis;liver graft;motor dysfunction;patient referral;pediatric patient;pediatrician;Wilson disease;endogenous compound;liver enzyme;Wilson disease protein;zinc,"Capone, K.;Azzam, R. K.",2018,November,http://dx.doi.org/10.3928/19382359-20181026-01,0,0,
3270,Tetrathiomolybdate induces dimerization of the metal-binding domain of ATPase and inhibits platination of the protein,"Tetrathiomolybdate (TM) is used in the clinic for the treatment of Wilson's disease by targeting the cellular copper efflux protein ATP7B (WLN). Interestingly, both TM and WLN are associated with the efficacy of cisplatin, a widely used anticancer drug. Herein, we show that TM induces dimerization of the metal-binding domain of ATP7B (WLN4) through a unique sulfur-bridged Mo2S6O2 cluster. TM expels copper ions from Cu-WLN4 and forms a copper-free dimer. The binding of Mo to cysteine residues of WLN4 inhibits platination of the protein. Reaction with multi-domain proteins indicates that TM can also connect two domains in the same molecule, forming Mo-bridged intramolecular crosslinks. These results provide structural and chemical insight into the mechanism of action of TM against ATPase, and reveal the molecular mechanism by which TM attenuates the cisplatin resistance mediated by copper efflux proteins.",article;cross linking;dimerization;drug resistance;human;metal binding;protein domain;Wilson disease;cisplatin;copper;copper ion;dimer;endogenous compound;molybdenum;sulfur;tetrathiomolybdic acid;Wilson disease protein,"Fang, T.;Chen, W.;Sheng, Y.;Yuan, S.;Tang, Q.;Li, G.;Huang, G.;Su, J.;Zhang, X.;Zang, J.;Liu, Y.",2019,14 Jan,http://dx.doi.org/10.1038/s41467-018-08102-z,0,0,
3271,Relative exchangeable copper: A valuable tool for the diagnosis of Wilson disease,"Background & Aims: Measuring of the relative exchangeable copper seems to be a promising tool for the diagnosis of Wilson disease. The aim of our study is to determine the performance of REC for the diagnosis of Wilson disease in a population of patients with chronic liver diseases. Method(s): Measuring of exchangeable serum copper levels and relative exchangeable copper was performed in a group of Wilson disease patients at diagnosis or at clinical deterioration because of non-compliance (group 1, n=9), a group of stable WD patients (group 2, n=40), and two groups of patients (adult and paediatric) followed for non-Wilsonian liver diseases (group 3, n=103 and group 4, n=49 respectively). Result(s): Exchangeable serum copper (N: 0.6-1.1 mumol/L) was significantly higher in group 1 (mean 2.2+/-0.7 mumol/L) compared to the other three groups: group 2=0.9+/-0.4 mumol/L, group 3=1.2+/-0.4 mumol/L, group 4=1.1+/-0.3 mumol/L (P<0.05). Relative exchangeable copper was significantly higher in Wilson disease patients group 1 and 2 (mean 52.6% and 43.8%) compared to patients suffering from other liver diseases (mean 7.1% and 5.9%) (P<0.05). Conclusion(s): Our study confirms that the determination of relative exchangeable copper is a highly valuable tool for the diagnosis of Wilson disease. Copyright © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",copper;diagnostic test;liver disease;Wilson disease;adolescent;adult;aged;article;ceruloplasmin blood level;child;cholestasis;chronic liver disease;controlled study;copper blood level;demography;female;human;major clinical study;male;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];unclassified drug;zinc derivative/dt [Drug Therapy];relative exchangeable copper/ec [Endogenous Compound],"Guillaud, O.;Brunet, A. S.;Mallet, I.;Dumortier, J.;Pelosse, M.;Heissat, S.;Rivet, C.;Lachaux, A.;Bost, M.",2018,Februaryy,http://dx.doi.org/10.1111/liv.13520,0,0,
3272,Evaluation of the accuracy of exchangeable copper and relative exchangeable copper (REC) in a mouse model of Wilson's disease,"Wilson's disease (WD) is caused by mutations in the ATP7B gene responsible for a toxic copper overload mainly in the liver and the central nervous system. Phenotypic heterogeneity may challenge the diagnostic confirmation. Exchangeable copper (CuEXC) has recently been proposed as a new marker of WD, and its ratio to the total serum copper (Cus), Relative Exchangeable Copper (REC = CuEXC/Cus), as a diagnostic marker. This study aimed to investigate whether this could be confirmed in Atp7b<sup>-/-</sup> mice, an engineered WD animal model. Atp7b<sup>-/-</sup> (n = 137) and wild type (WT; n = 101) mice were investigated under the same conditions at 6-8, 20, 39, or 50 weeks of age. Twenty-four Atp7b<sup>-/-</sup> mice received D-penicillamine treatment from 39 to 50 weeks of age. Serum and liver [histology and intrahepatic copper (IHCu)] data were evaluated. In the WT group, all serum and liver data were normal. Atp7b<sup>-/-</sup> livers developed a chronic injury from isolated moderate inflammation (6-8 weeks: 16/33 = 48%) to inflammatory fibrosis with cirrhosis (50 weeks: 25/25 = 100% and 16/25 = 64% respectively). Cus and CuEXC increased until week 39, whereas IHCu and REC were stable with increasing age and much higher than in WT mice (mean +/- SD: 669 +/- 269 vs. 13 +/- 3 mug/g dry liver and 39 +/- 12 vs. 11 +/- 3%, respectively). A threshold value of 20% for REC provided a diagnostic sensitivity and specificity of 100%, regardless of sex, age, or the use of D-penicillamine. Eleven weeks of 100 mg/kg D-penicillamine reduced liver fibrosis (p = 0.001), IHCu (p = 0.026) and CuEXC (p = 0.175). In conclusion, this study confirms REC as a WD diagnostic marker in a mouse model of chronic liver disease caused by copper overload. Further studies are needed to assess the usefulness of CuEXC to monitor the evolution of WD, particularly during treatment. Copyright © 2018",Atp7b<sup>-/-</sup> mice;Cirrhosis;Diagnostic test;Exchangeable copper;rec;age;animal experiment;animal model;animal tissue;article;controlled study;copper blood level;diagnostic accuracy;diagnostic test accuracy study;female;histology;infant;inflammation;liver cirrhosis;liver fibrosis;liver level;male;mouse;nonhuman;priority journal;sensitivity and specificity;sex;Wilson disease/di [Diagnosis];biological marker/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine;unclassified drug;Wilson disease protein;ATP7B gene;exchangeable copper/ec [Endogenous Compound];relative exchangeable copper/ec [Endogenous Compound],"Heissat, S.;Harel, A.;Um, K.;Brunet, A. S.;Hervieu, V.;Guillaud, O.;Dumortier, J.;Lachaux, A.;Mintz, E.;Bost, M.",2018,December,http://dx.doi.org/10.1016/j.jtemb.2018.06.013,0,0,
3273,"Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice","Background: Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson's disease, and decreased the severity of autoimmune arthritis in mice. Objective(s): In this report, we evaluated the effects of TM in a mouse model for psoriasis. Method(s): Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors. Result(s): Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3. Conclusion(s): These findings are strong evidence that TM can inhibit psoriasis in the model. Copyright © 2018 Japanese Society for Investigative Dermatology",Copper;Imiquimod;Psoriasis;Tetrathiomolybdate;animal cell;animal experiment;animal model;animal tissue;antigen expression;article;C57BL 6 mouse;controlled study;cytokine production;dermatitis;drug effect;enzyme linked immunosorbent assay;epidermis;human;human cell;imiquimod-induced psoriasis/dt [Drug Therapy];immunohistochemistry;keratinocyte;lymphatic drainage;male;mouse;murine model;nonhuman;priority journal;protein phosphorylation;spleen cell;gamma interferon/ec [Endogenous Compound];interleukin 17/ec [Endogenous Compound];interleukin 2/ec [Endogenous Compound];interleukin 21/ec [Endogenous Compound];interleukin 22/ec [Endogenous Compound];interleukin 6/ec [Endogenous Compound];Ki 67 antigen/ec [Endogenous Compound];mitogen activated protein kinase 1/ec [Endogenous Compound];mitogen activated protein kinase 3/ec [Endogenous Compound];STAT3 protein/ec [Endogenous Compound];tetrathiomolybdic acid/dt [Drug Therapy],"Hsu, P. Y.;Yen, H. H.;Yang, T. H.;Su, C. C.",2018,October,http://dx.doi.org/10.1016/j.jdermsci.2018.08.003,0,0,
3274,A case report: Co-occurrence of Wilson disease and oculocutaneous albinism in a Chinese patient,"RATIONALE: Both Wilson disease (WD) and Oculocutaneous Albinism (OCA) are rare autosomal recessive disorders that are caused by mutations on chromosome 13 and chromosome 11, respectively. Here, we report on a patient with coexisting WD and OCA, initially presenting episodes of tremors. PATIENT CONCERNS: WD is a disorder of copper metabolism. The main sites of copper accumulation are the liver and the brain, resulting in hepatic symptoms. OCA is a disorder of melanin biosynthesis, characterized by a generalized reduction in pigmentation of the eyes (oculo-), skin (-cutaneous), and hair. DIAGNOSIS: The diagnosis of WD was confirmed by neurological symptoms, metabolism tests, and MRI scans. Interestingly, the patient also had very light skin color, blond hair and eyebrows, and dark brown eyelashes and irises. Because the association of dermatologic signs in WD has rarely been reported, OCA was highly suspected based on these clinical findings. Genetic analysis was subsequently conducted, and the results revealed the p. (Arg778Leu) mutation in 1 allele and the p. (Asn1270Ser) mutation in the other allele of the ATP7B gene, confirming the diagnosis of WD; the p. (D456fs) mutation in 1 allele and the p. (R299H) mutation in the other allele of the TYR gene, confirming the diagnosis of OCA. The family history was positive for WD with a 14-year-old younger brother also being diagnosed with it. Her parents are negative for OCA and WD. INTERVENTIONS: Sodium dimercaptopropanesulfonate (DMPS) was given during hospitalization. D-penicillamine and zinc sulfate treatment was initiated after discharge for long-term control. OUTCOME(S): Postural and intention tremor disappeared, and other symptoms and signs markedly improved after treatment. LESSONS: In this study, we reported on the first case of a child who simultaneously presented WD and OCA, bringing up the possibility of a presumable link between these 2 rare diseases.",Asian continental ancestry group;case report;complication;diagnostic imaging;female;genetics;human;metabolism;mutation;nuclear magnetic resonance imaging;oculocutaneous albinism/di [Diagnosis];procedures;treatment outcome;Wilson disease/dt [Drug Therapy];young adult;astringent agent/dt [Drug Therapy];chelating agent/dt [Drug Therapy];penicillamine/ad [Drug Administration];penicillamine/dt [Drug Therapy];unithiol/ad [Drug Administration];unithiol/dt [Drug Therapy];zinc sulfate/ad [Drug Administration];zinc sulfate/dt [Drug Therapy],"Rao, R.;Shu, S.;Han, Y. Z.;Chiu, Y. J.;Han, Y. S.",2018,01 Dec,http://dx.doi.org/10.1097/MD.0000000000013744,0,0,
3275,Feature Article: Trientine selectively delivers copper to the heart and suppresses pressure overload-induced cardiac hypertrophy in rats,"Dietary copper supplementation reverses pressure overload-induced cardiac hypertrophy by copper replenishment in the heart. A copper-selective chelator, trientine (triethylenetetramine [TETA]), reverses left ventricular hypertrophy associated with diabetes also by copper replenishment in the heart. The present study was undertaken to address the critical issue how TETA delivers copper to the heart. Adult male Sprague-Dawley rats were subjected to transverse aortic constriction (TAC) to induce cardiac hypertrophy. Eight weeks after the TAC surgery, cardiac hypertrophy was developed and copper content in the heart was reduced. TETA was then administrated by gavage in two different dosages (21.9 or 87.6 mg/kg day) for six weeks. The results showed that in the lower dosage, TETA replenished copper contents in the heart, along with a decrease in the copper concentration in the blood and kidney, and an increase in the urine. In the higher dosage, TETA did not replenish copper contents in the heart, but markedly increased copper concentrations in the urine and decreased those in the blood and kidney. Neither lower nor higher TETA dosage altered copper concentrations in other organs. Corresponding to myocardial copper replenishment, the lower dose TETA suppresses cardiac hypertrophy, as judged by a reduction in the left ventricle wall thickness and a decrease in the heart size, and diminished cardiac fibrosis, as reflected by a decrease in collagen I content. TETA in the higher dose not only did not suppress cardiac hypertrophy, but also caused cardiac hypertrophy in sham-operated rats. TETA-mediated myocardial copper restoration is independent of copper transporter-1 or -2 but related to an energy-dependent transportation. This study demonstrates that low-dose TETA functions as a copper chaperone, selectively delivering copper to the copper-deprived heart through an active transportation; in higher doses, TETA simply retains its chelator function, removing copper from the body by urinary excretion. Impact statement: Our study reveals that TETA, traditionally regarded as a copper chelator, in lower doses delivers copper selectively to the heart through a mechanism independent of copper transporter-1 or -2. Copper supplementation by a lower dose of TETA suppresses pressure overload-induced cardiac hypertrophy. Since ischemic heart disease and hypertrophic cardiomyopathy are accompanied by myocardial copper loss, this approach of using a lower dose of TETA to supplement copper to the heart would help treat the disease condition of patients with such cardiac events. Copyright © 2018 by the Society for Experimental Biology and Medicine.",cardiac hypertrophy;cardiac selective;Copper;copper transporters;suppression;trientine;adult;animal experiment;animal model;animal tissue;aortic arch;article;atomic absorption spectrometry;blood flow velocity;carotid artery;controlled study;Doppler flowmetry;drug megadose;echocardiography;endotracheal intubation;experimental cardiac hypertrophy/dt [Drug Therapy];gene expression;heart ejection fraction;heart left ventricle overload;heart left ventricle volume;heart left ventricle wall;heart muscle contractility;heart muscle fibrosis;heart size;heart surgery;heart ventricle hypertrophy;immunohistochemistry;low drug dose;male;microscopy;nonhuman;pain/dt [Drug Therapy];rat;real time polymerase chain reaction;reverse transcription polymerase chain reaction;thoracic cavity;Western blotting;Wilson disease;beta actin/ec [Endogenous Compound];carrier proteins and binding proteins/ec [Endogenous Compound];collagen type 1/ec [Endogenous Compound];complementary DNA/ec [Endogenous Compound];dezocine/dt [Drug Therapy];dezocine/im [Intramuscular Drug Administration];trientine/dt [Drug Therapy];unclassified drug;spectrophotometer;transverse aortic constriction;copper transporter 1/ec [Endogenous Compound];copper transporter 2/ec [Endogenous Compound];iCE3500,"Liu, J.;Chen, C.;Liu, Y.;Sun, X.;Ding, X.;Qiu, L.;Han, P.;James Kang, Y.",2018,01 Oct,http://dx.doi.org/10.1177/1535370218813988,0,0,
3276,Unusual osseous presentation of Wilson disease in a child,,academic achievement;acute lymphoblastic leukemia/di [Diagnosis];anemia/di [Diagnosis];arthralgia;article;blood cell count;bone marrow biopsy;bone pain/di [Diagnosis];bone pain/dt [Drug Therapy];bone radiography;case report;Caucasian;caudate nucleus;child;clinical article;clinical examination;dual energy X ray absorptiometry;dystonia;echography;elastography;exon;extrapyramidal syndrome/di [Diagnosis];eye examination;female;fibula;foot;gene mutation;gene sequence;hand tremor;hip;homozygote;human;human cell;human tissue;juvenile rheumatoid arthritis/di [Diagnosis];knee;leg pain;leukocyte;liver cirrhosis/di [Diagnosis];liver transplantation;medical history;metaphysis;neurologic examination;nuclear magnetic resonance imaging;osteopenia/di [Diagnosis];physical examination;positron emission tomography;putamen;school child;thrombocyte;tibia;visual system parameters;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];wrist;arginine/ec [Endogenous Compound];calcium/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];cytosine/ec [Endogenous Compound];guanine/ec [Endogenous Compound];nonsteroid antiinflammatory agent/dt [Drug Therapy];parathyroid hormone/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];phosphorus/ec [Endogenous Compound];threonine/ec [Endogenous Compound];thymine/ec [Endogenous Compound];tryptophan/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];ATP7B gene;kayser fleischer ring;metaphyseal lucent band,"Almes, M.;Fayard, C.;Gonzales, E.;Hermeziu, B.;Bellesme, C.;Jacquemin, E.;Kone-Paut, I.;Adamsbaum, C.;Dusser, P.",2017,December,http://dx.doi.org/10.1016/j.arcped.2017.09.005,0,0,
3277,Elastosis perforans serpiginosa: causes and associated disorders,"Background: Elastosis perforans serpiginosa (EPS) is an uncommon cutaneous disorder classified under perforating diseases (PD); a group of dermatoses with transepidermal extrusion of collagen or elastic tissue. Three EPS subtypes have been reported that differ according to aetiology, associated diseases, and histopathological features. Herein, we report a systematic review of the literature, as well as a case of a 41-year-old woman with Wilson disease treated with penicillamine (PCM), who developed EPS after 11 years of drug intake. Objective(s): To analyse and characterise EPS subtypes based on an evaluation of potential different histological patterns. Material(s) and Method(s): A systematic literature search in Pubmed was performed to identify articles describing EPS. Result(s): Apeculiar histological patternwas identified in EPS PCM-related patients, either in affected or unaffected skin samples. Using specific elastic fibre stains (Verhoeff-van Gieson, Weigert, and Orcein), fibres appeared with an irregular surface with thorn-like protrusion, probably due to weaker fibre cross-links, making them unable to re-expand after contraction along their long axis. Interestingly, similar histological patterns have also been reported in elastic tissues of vessel walls of the lungs and upper respiratory tract, joints, visceral adventitia, and kidney. Conclusion(s): A distinctive histological pattern of PCMrelated EPS is observed in affected and normal-appearing skin, as well as extracutaneous elastic tissue, suggesting serious potential widespread drug-induced systemic elastolytic damage. Copyright © 2018, John Libbey Eurotext.",D-penicillamine;elastosis perforans serpiginosa;lumpybumpy;perforating disease;systemic elastolytic damage;Wilson disease;acanthosis;case report;cell infiltration;clinical article;computer assisted tomography;elastosis/dt [Drug Therapy];eye examination;female;histopathology;human;human tissue;hyperkeratosis;muscle hypotonia;review;skin biopsy;systematic review;visual system examination;Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];methylprednisolone/tp [Topical Drug Administration];penicillamine/dt [Drug Therapy];retinoic acid/dt [Drug Therapy];retinoic acid/tp [Topical Drug Administration];zinc sulfate/dt [Drug Therapy];zinc sulfate/po [Oral Drug Administration];elastosis perforans serpiginosa/di [Diagnosis],"Montesu, M. A.;Onnis, G.;Gunnella, S.;Lissia, A.;Satta, R.",2018,01 Jul,http://dx.doi.org/10.1684/ejd.2018.3355,0,0,
3278,Implications of manganese in chronic acquired hepatocerebral degeneration,"Neurological symptoms can be one of the over-riding symptoms in patients with liver cirrhosis. Patients can present with subtle changes in mood or neurological function due to hepatic encephalopathy (HE), to more severe presentations including stupor and coma. While HE, in its severe form, can be clinically easy to diagnose, more subtle forms may be more difficult to recognize. Other neurological diseases may indeed be overlooked in the context of cirrhosis or confuse the physician regarding the diagnosis. Chronic acquired hepatocerebral degeneration (CAHD) is an uncommon problem occurring in patients with cirrhosis characterised by a Par-kinsonian-like neurological presentation with damage to the brain secondary to manganese (Mn) deposition. Here we describe a case of a patient with a neurological presentation of liver disease with a review of the current CAHD literature. In conclusion, CAHD is a rare condition occurring in liver cirrhosis that should always be considered in patients with neurological manifestations of chronic liver disease. Copyright © 2019, Fundacion Clinica Medica Sur. All rights reserved.",Chronic acquired hepatocerebral degeneration;Cirrhosis;Manganese;adult;article;ataxic gait;case report;Chinese;cholecystectomy;clinical article;disease course;disease duration;dysarthria;dysphagia;falling;histopathology;human;human cell;liver biopsy;liver cirrhosis/co [Complication];liver cirrhosis/di [Diagnosis];liver transplantation;male;manganese blood level;middle aged;Model For End Stage Liver Disease Score;neurological complication/co [Complication];neurological complication/di [Diagnosis];nuclear magnetic resonance imaging;Parkinson disease/dt [Drug Therapy];splenomegaly/di [Diagnosis];tremor;visual disorder;Wilson disease/dt [Drug Therapy];x-ray computed tomography;carbidopa plus levodopa/dt [Drug Therapy];manganese/to [Drug Toxicity];manganese/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/po [Oral Drug Administration];zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];chronic acquired hepatocerebral degeneration/co [Complication];chronic acquired hepatocerebral degeneration/di [Diagnosis],"Rajoriya, N.;Brahmania, M.;Feld, J. J.",2019,January-February,http://dx.doi.org/10.5604/01.3001.0012.7938,0,0,
3279,Acute liver failure due to wilson disease: Eight years of the national liver transplant program in Uruguay,"Introduction and aim. Wilson's disease (WD) is an uncommon cause of acute liver failure (ALF). Our aim was to describe clinical features, diagnostic findings, treatments, and outcomes of patients with ALF due to WD. Material and methods. Retrospective medical record reviews of all patients with ALF due to WD in eight years in Uruguay. Results. WD was the cause of six (15%) of thirty-nine ALF cases. All patients were females, with a mean age of 18 years. Four patients presented with hyperacute liver failure and two with acute failure. Jaundice was the main complaint of all patients. Mean total bilirubin (TB), alkaline phosphatase (AP), AST, and ALT were 27.5 mg/dL, 45.5 IU/l, 156 IU/L, and 51 IU/L, respectively. Ceruloplasmin levels were low in four patients, urinary cooper was high in four, and two had Kayser-Fleischer rings. All patients had Coombs-negative hemolytic anemia, acute kidney injury, histochemical identifiable copper, and advanced fibrosis on liver histology. The average MELD score was 36. All patients were treated with d-penicillamine and listed for urgent liver transplantation (LT). Prometheus was performed in one patient. Three patients died: two without LT and one after LT. Three patients survived: one without LT (New Wilson Index < 11) and two with LT. The referral time to the program and the total time (referral plus waiting list time) were longer for non-survivors than for survivors (14 vs. 3 days and 23 vs. 8 respectively). Conclusion. All cases had typical clinical, analytical and histopathology characteristics. Early referral was determinant of prognosis. Copyright © 2019, Fundacion Clinica Medica Sur. All rights reserved.",Chelation therapy;Liver transplantation;Mortality;Referral time;Waiting list time;acute kidney failure;acute liver failure/co [Complication];acute liver failure/su [Surgery];adolescent;adult;alanine aminotransferase blood level;alkaline phosphatase blood level;article;aspartate aminotransferase blood level;bilirubin blood level;child;clinical article;clinical feature;clinical outcome;controlled study;cornea disease;descriptive research;diagnostic test;disease severity;female;hemolytic anemia;histochemistry;human;human cell;human tissue;jaundice;liver fibrosis/co [Complication];liver fibrosis/di [Diagnosis];medical record review;Model For End Stage Liver Disease Score;patient care;patient referral;rating scale;retrospective study;school child;survival;urine level;Uruguay;Wilson disease/dt [Drug Therapy];young adult;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];artificial liver;kayser fleischer ring;New Wilson Index;Prometheus,"Mainardi, V.;Rando, A. E. K.;Valverde, M.;Olivari, D.;Castelli, J.;Rey, G.;Gerona, S.",2019,January-February,http://dx.doi.org/10.5604/01.3001.0012.7911,0,0,
3280,Tetrathiomolybdate inhibits the reaction of cisplatin with human copper chaperone Atox1,"Cisplatin is a widely used anticancer drug in clinic, and ammonium tetrathiomolybdate ([(NH<inf>4</inf>)<inf>2</inf>MoS<inf>4</inf>], TM) is a copper chelator used in clinic for the treatment of Wilson's disease. Recently, TM has been found to enhance the therapeutic effect of cisplatin; however, the origin of this effect is not clear. Here we found that TM can inhibit the reaction of cisplatin with Cu-Atox1 and prevent the protein unfolding and aggregation induced by cisplatin. Although Ag(i) binds to Atox1 in a way similar to Cu(i)-Atox1, TM does not prevent the reaction of Ag-Atox1 with cisplatin. This result indicates that the formation of a Mo-centered trimeric protein cluster in the TM-Cu-Atox1 system plays a role in the inhibitory effect. This work provides new insights into the mechanism by which TM enhances the cytotoxic efficacy of cisplatin and helps to circumvent cisplatin resistance of tumor cells. Copyright © 2018 The Royal Society of Chemistry.",article;cancer resistance;drug potentiation;electrospray mass spectrometry;heteronuclear single quantum coherence;human;priority journal;protein aggregation;protein binding;protein expression;protein unfolding;chaperone/ec [Endogenous Compound];cisplatin/cb [Drug Combination];cisplatin/it [Drug Interaction];copper;glutathione;tetrathiomolybdate ammonium;tetrathiomolybdic acid/cb [Drug Combination];tetrathiomolybdic acid/it [Drug Interaction];unclassified drug;Atox1 protein/ec [Endogenous Compound],"Tian, Y.;Fang, T.;Yuan, S.;Zheng, Y.;Arnesano, F.;Natile, G.;Liu, Y.",2018,May,http://dx.doi.org/10.1039/c8mt00084k,0,0,
3281,Pediatric Wilson's disease: Findings in different presentations. A cross-sectional study,"BACKGROUND: Wilson's disease (WD) may present with different manifestations: from an asymptomatic state to liver cirrhosis. Here, we aimed to evaluate clinical presentations and laboratory findings and prognoses among WD cases. DESIGN AND SETTING: Cross-sectional study based on patients' records from the university hospital, Inonu University, Malatya, Turkey. METHOD(S): The medical records of 64 children with WD were evaluated focusing on the clinical, laboratory and liver biopsy findings in different clinical presentations. RESULT(S): The mean age at diagnosis was 8.6 +/- 3.26 years (range 3.5-17) and mean length of follow-up was 2.49 years (range 0-9). There were 18 cases (28.1%), 12 (18.8%), 9 (14.1%) and 6 (9.4%) of chronic liver disease, fulminant liver failure, neurological WD and acute hepatitis, respectively. Nineteen (29.7%) were asymptomatic. The most common sign and laboratory finding were jaundice (45.3%) and hypertransam-inasemia (85.9%), respectively. The lowest serum zinc level was found in the fulminant liver failure group (P = 0.035). Hepatosteatosis was detected in 35% of the 20 patients who underwent liver biopsy. Among those with hepatosteatosis, 57.1% were asymptomatic. While 35% had copper staining, 25% presented iron accumulation in liver biopsies. Nine cases underwent liver transplantation and seven of these presented fulminant liver failure (77.8%). CONCLUSION(S): The presentation, symptoms and signs of our cases were similar to those in previously reported series, except for the high proportion of fulminant WD cases. Further studies are needed to clarify the relationship between zinc levels and development of a fulminant course and between iron status and WD. Copyright © 2018 by Associacao Paulista de Medicina.",Child;Hepatolenticular degeneration;Iron;Zinc;acute hepatitis;article;ascites;brain disease;chronic hepatitis;chronic liver disease;clinical evaluation;clinical feature;Coombs test;cross-sectional study;diagnostic accuracy;diagnostic test accuracy study;disease course;echography;fatty liver;female;follow up;fulminant hepatic failure;gastrointestinal endoscopy;hemolytic anemia;hepatomegaly;histopathology;human;hypertransaminasemia;hypouricemia;international normalized ratio;jaundice;leukocyte count;liver biopsy;liver transplantation;major clinical study;male;mental disease;mortality rate;neurologic disease;nuclear magnetic resonance imaging;predictive value;prognosis;retrospective study;school child;scoring system;sensitivity and specificity;splenomegaly;Turkey (republic);Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];high density lipoprotein cholesterol/ec [Endogenous Compound];iron/ec [Endogenous Compound];penicillamine/ec [Endogenous Compound];trientine/ec [Endogenous Compound];uric acid/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Selimoglu, M. A.;Varol, F. I.;Gungor, S.",2018,July-August,http://dx.doi.org/10.1590/1516-3180.2018.0210230718,0,0,
3282,Recurrent stroke-like episodes of Wilson disease with a novel Val176fs mutation,,adolescent;case report;cerebrovascular accident;clinical article;diagnostic error;DNA sequence;electromyography;gene mutation;human;human tissue;letter;male;MELAS syndrome;muscle biopsy;neurologic disease;nuclear magnetic resonance imaging;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Pan, L.;Ding, D.;Leng, H.;Deng, X.;Xu, Y.",2018,01 May,http://dx.doi.org/10.1007/s10072-018-3257-x,0,0,
3283,Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. alpha-Lipoic acid as a potential anti-copper agent,"Wilson disease is an autosomal recessive genetic disorder caused by loss-of-function mutations in the P-type copper ATPase, ATP7B, which leads to toxic accumulation of copper mainly in the liver and brain. Wilson disease is treatable, primarily by copper-chelation therapy, which promotes copper excretion. Although several de-coppering drugs are currently available, their Cu(I)-binding affinities have not been quantitatively characterized. Here we determined the Cu(I)-binding affinities of five major de-coppering drugs - D-penicillamine, trientine, 2,3-dimercapto-1-propanol, meso-2,3-dimercaptosuccinate and tetrathiomolybdate - by exploring their ability to extract Cu(I) ions from two Cu(I)-binding proteins, the copper chaperone for cytochrome c oxidase, Cox17, and metallothionein. We report that the Cu(I)-binding affinity of these drugs varies by four orders of magnitude and correlates positively with the number of sulfur atoms in the drug molecule and negatively with the number of atoms separating two SH groups. Based on the analysis of structure-activity relationship and determined Cu(I)-binding affinity, we hypothesize that the endogenous biologically active substance, alpha-lipoic acid, may be suitable for the treatment of Wilson disease. Our hypothesis is supported by cell culture experiments where alpha-lipoic acid protected hepatic cells from copper toxicity. These results provide a basis for elaboration of new generation drugs that may provide better therapeutic outcomes.","apoptosis;cell line;cell proliferation;cytology;drug effect;human;liver cell;metabolism;Wilson disease/dt [Drug Therapy];carrier protein;chelating agent/pd [Pharmacology];copper/to [Drug Toxicity];metallothionein;penicillamine/pd [Pharmacology];thioctic acid/pd [Pharmacology];thioctic acid/dt [Drug Therapy];trientine/pd [Pharmacology];COX17 protein, human","Smirnova, J.;Kabin, E.;Jarving, I.;Bragina, O.;Tougu, V.;Plitz, T.;Palumaa, P.",2018,23 Jan,http://dx.doi.org/10.1038/s41598-018-19873-2,0,0,
3284,"Bridging east with west of Europe - A comparison of orphan drugs policies in Poland, Russia and the Netherlands","The goal of this article is to provide an in-depth review of rare disease policies and the reimbursement of ODs in 3 European countries, two EU members (Poland, the Netherlands) and a non-EU one (Russia). A review of publicly available information on rare disorder policies and HTA processes was performed. Experts were consulted in case of unclear or scarce information. Russia has a five times higher frequency threshold for its rare disease definition than Poland and the Netherlands (both using the EU definition). The Netherlands has vastly increased its disease registries by instituting 300 expert centers via its National Plan, in Poland there are only 6 registries while in Russia one central registry exists. All 3 countries have an HTA process in place, however, the Russian one is relatively undeveloped. Access to ODs in the Netherlands is the broadest with 80 out of 83 EMA approved ODs reimbursed in 2015; Poland reimbursed 49, whereas Russia reimbursed 4 on the federal level and 43 in Moscow region. In all countries, new rare disease policies are under development. The availability of healthcare system solutions and the reimbursement of ODs differs greatly between all 3 countries. Even though both states are EU member with common regulations and access to EMA approved drugs, marked differences exist between Poland and the Netherlands in the range of policies, access to treatments and screening programs. Copyright © 2018 Institute of Chemical Technology. All rights reserved.",Disease registries;National plan for rare diseases;Newborn screening;Orphan drugs;Policy;Rare diseases;Reimbursement;aplastic anemia/dt [Drug Therapy];article;autoimmune hemolytic anemia/dt [Drug Therapy];blood clotting factor 10 deficiency/dt [Drug Therapy];blood clotting factor 7 deficiency/dt [Drug Therapy];comparative study;complement disorder/dt [Drug Therapy];disease registry;European Medicines Agency;Fabry disease/dt [Drug Therapy];health care access;health care policy;health care system;hemolytic uremic syndrome/dt [Drug Therapy];Hunter syndrome/dt [Drug Therapy];Hurler syndrome/dt [Drug Therapy];juvenile rheumatoid arthritis/dt [Drug Therapy];Netherlands;Niemann Pick disease/dt [Drug Therapy];paroxysmal nocturnal hemoglobinuria/dt [Drug Therapy];Poland;precocious puberty/dt [Drug Therapy];pulmonary hypertension/dt [Drug Therapy];rare disease/di [Diagnosis];rare disease/dt [Drug Therapy];rare disease/ep [Epidemiology];Russian Federation;Wilson disease/dt [Drug Therapy];adalimumab/dt [Drug Therapy];agalsidase alfa/dt [Drug Therapy];aminocaproic acid/dt [Drug Therapy];blood clotting factor/dt [Drug Therapy];blood clotting factor 7/dt [Drug Therapy];bosentan/dt [Drug Therapy];complement component C1s inhibitor/dt [Drug Therapy];cyclosporine/dt [Drug Therapy];danazol/dt [Drug Therapy];deferasirox/dt [Drug Therapy];eculizumab/dt [Drug Therapy];eltrombopag/dt [Drug Therapy];etanercept/dt [Drug Therapy];icatibant/dt [Drug Therapy];iduronate 2 sulfatase/dt [Drug Therapy];iloprost/dt [Drug Therapy];laronidase/dt [Drug Therapy];leflunomide/dt [Drug Therapy];methotrexate/dt [Drug Therapy];miglustat/dt [Drug Therapy];orphan drug/dt [Drug Therapy];penicillamine/dt [Drug Therapy];recombinant blood clotting factor 7a/dt [Drug Therapy];romiplostim/dt [Drug Therapy];sildenafil/dt [Drug Therapy];thymocyte antibody/dt [Drug Therapy];tocilizumab/dt [Drug Therapy];triptorelin/dt [Drug Therapy];unindexed drug;zinc sulfate/dt [Drug Therapy],"Czech, M.;Baran-Kooiker, A.;Holownia-Voloskova, M.;Kooiker, C.;Sykut-Cegielska, J.",2018,,http://dx.doi.org/10.32383/appdr/90995,0,0,
3285,Predictors of seizure in Wilson disease: A clinico-radiological and biomarkers study,"Background: There is paucity of studies on predictors of seizures in Wilson disease with neurological manifestation (WDNM), and none has evaluated the role of copper (Cu) induced oxidative stress, proinflammatory and excitotoxicity in the genesis of seizure. Objective(s): To report frequency, refractoriness, and outcome of seizure in WDNM. We also evaluate role of Cu induced oxidative stress, excitotoxicity and cytokines in predicting seizures. Method(s): The diagnosis of WDNM was based on clinical, MRI, KF ring and 24 h urinary Cu. Detailed clinical examination including severity of WD, occurrence of seizure, seizure semiology, antiepileptic drug (AED) and breakthrough seizures were noted. Cranial MRI and electroencephalography findings were noted. Serum free-Cu, oxidative stress markers (glutathione, total antioxidant capacity, malondialdehyde), glutamate and cytokines (interleukin 6, 8 and 10 and tumour necrosis factor alpha) were measured by atomic absorption spectrophotometer, spectrophotometer, fluorometer and flow cytometer respectively, and correlated with seizures. Patients were treated with zinc with or without penicillamine, and those with epilepsy received second-generation antiepileptic drugs (AEDs). Result(s): Out of 110 patients with WDNM, 16(14.5%) had seizures; focal in 11(68.7%) and generalized in 5(31.3%). Patients with seizure had higher serum free-Cu (35.87 +/- 1.34 vs 31.72 +/- 0.68; P = 0.02), severe dystonia (P = 0.04), and more frequent cortical (100% vs 6.4%; P < 0.01) and subcortical (81.3% vs 20.2%; P < 0.01) lesions on MRI compared to those without seizure. Oxidative stress markers (glutathione, total antioxidant capacity, malondialdehyde), cytokines and glutamate were elevated in WDNM compared to controls. On multivariate logistic regression analysis, cortical involvement (OR = 105.49; 95%CI = 8.74-1272.39; P < 0.01) and number of MRI lesions (OR = 1.99; 95% CI = 1.11-3.57; P = 0.02) were independent predictors of seizure. The seizures were controlled with single and dual AEDs in seven patients each, and two patients needed three AEDs. All the patients had seizure remission for a median follow up of 66(24-180) months. Conclusion(s): About one-sixth WDNM patients have seizures especially in those with cortical and extensive MRI lesions. Seizures are easily controlled by AEDs. Copyright © 2018 Elsevier B.V.",Antiepileptic drug;Copper;Magnetic;Oxidative stress;Resonance imaging;Seizure;Wilson disease;adolescent;adult;article;atomic absorption spectrometry;brain cortex;brain radiography;child;clinical examination;clinical outcome;controlled study;copper blood level;copper metabolism;disease marker;disease severity;drug dose increase;dystonia/dt [Drug Therapy];electroencephalography;excitotoxicity/di [Diagnosis];female;flow cytometry;follow up;human;major clinical study;male;neurologic disease/di [Diagnosis];neurologic disease/dt [Drug Therapy];nuclear magnetic resonance imaging;prediction;priority journal;prospective study;remission;retrospective study;school child;seizure/di [Diagnosis];seizure/dt [Drug Therapy];spectrophotometry;symptom;urinalysis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];young adult;alpha tocopherol;antioxidant/ec [Endogenous Compound];ascorbic acid;baclofen/dt [Drug Therapy];calcium/cb [Drug Combination];carbamazepine/dt [Drug Therapy];clobazam/dt [Drug Therapy];cytokine/ec [Endogenous Compound];gabapentin/dt [Drug Therapy];glutamic acid/ec [Endogenous Compound];glutathione/ec [Endogenous Compound];interleukin 10/ec [Endogenous Compound];interleukin 6/ec [Endogenous Compound];interleukin 8/ec [Endogenous Compound];levetiracetam/dt [Drug Therapy];malonaldehyde/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];phenytoin/dt [Drug Therapy];pyridoxine;tetrabenazine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];tumor necrosis factor/ec [Endogenous Compound];valproic acid/dt [Drug Therapy];vitamin D/cb [Drug Combination];zinc/cb [Drug Combination];zinc/dt [Drug Therapy];nuclear magnetic resonance scanner;Wilson disease with neurological manifestation/di [Diagnosis];Wilson disease with neurological manifestation/dt [Drug Therapy],"Kalita, J.;Misra, U. K.;Kumar, V.;Parashar, V.",2019,March,http://dx.doi.org/10.1016/j.neuro.2018.12.005,0,0,
3286,An unusual and devastating presentation of neurologic Wilson's disease with extensive brain MRI lesions,,adult;akinetic mutism/di [Diagnosis];case report;central pontine myelinolysis/di [Diagnosis];clinical article;clinical feature;computer assisted tomography;decubitus;disease association;disease duration;drug dose titration;drug effect;electroencephalography;fatality;human;intensive care;letter;male;neuroleptic malignant syndrome/di [Diagnosis];nuclear magnetic resonance imaging;periaqueductal gray matter;physical examination;physiotherapy;protein blood level;schizophrenia/di [Diagnosis];schizophrenia/dt [Drug Therapy];sepsis/co [Complication];slit lamp microscopy;tonic clonic seizure/di [Diagnosis];tonic clonic seizure/dt [Drug Therapy];tremor/di [Diagnosis];white matter lesion/di [Diagnosis];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/th [Therapy];young adult;bromocriptine/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];levodopa/dt [Drug Therapy];olanzapine/dt [Drug Therapy];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];valproic acid/dt [Drug Therapy],"Belkhribchia, M. R.;Belabbes, S.;Loukili, M.;El Hasni, I.;El Makkaoui, M.",2018,June,http://dx.doi.org/10.1016/j.lpm.2018.03.015,0,0,
3287,Advances in treatment of Wilson disease,"Background: Wilson disease (WD) is an inherited neurometabolic disorder that results in excessive copper deposition in the liver and the brain, affecting children and young adults. Without treatment the disease is invariably fatal. Though treatments for WD have been available since the 1950s, the disease continues to be associated with considerable morbidity and mortality because of missed diagnosis, and delayed or inadequate treatment. In this paper we survey WD-related literature in order to review recent advances in WD treatment. Method(s): We performed a literature search using the PubMed database for articles relating to WD and its medical treatment. We reviewed the articles, and crossreferences of relevant articles, to summarize the current practices for treatment of WD. Result(s): The survey shows that if WD is properly treated, in most patients the liver can be stabilized, even severe neurological disability reversed, and patients can resume normal lives. Discussion(s): Medical treatment for WD includes use of copper chelators (penicillamine, trientine, dimercaprol, dimercaptopropane sulfonate, and ammonium tetrathiomolybdate) and drugs that decrease gastrointestinal copper absorption. Our knowledge of the treatment approaches has benefited from the large systematic clinical studies that have been conducted over the last decade. For each drug used to treat WD, we surveyed its development, indication for use, dosing, efficacy, and adverse effects. Copyright © 2018 Aggarwal et al.",Dimercaprol;Penicillamine;Tetrathiomolybdate;Trientine;Wilson disease;Zinc;angiogenesis;blood brain barrier;chelation;copper deficiency;copper metabolism;diet restriction;drug bioavailability;fibrosis;gastrointestinal absorption;gene mutation;hematoma;human;inflammation;liver dysfunction;mortality;nuclear magnetic resonance imaging;pregnancy;priority journal;review;toxicity;urinary excretion;Wilson disease/dt [Drug Therapy];amine;dimercaprol/dt [Drug Therapy];metallothionein/ec [Endogenous Compound];molybdenum;penicillamine/dt [Drug Therapy];spermidine;tetrathiomolybdate ammonium/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];tocopherol;trientine/dt [Drug Therapy];unithiol/dt [Drug Therapy];zinc derivative/dt [Drug Therapy],"Aggarwal, A.;Bhatt, M.",2018,,http://dx.doi.org/10.7916/D841881D,0,0,
3288,Wilson's disease: a reversible cause of ataxia,,adult;ataxic gait;bradykinesia;case report;cerebellar ataxia/di [Diagnosis];cerebellar ataxia/dt [Drug Therapy];cerebellum atrophy;cerebrospinal fluid analysis;clinical article;follow up;gait disorder;genetic analysis;hand tremor;human;letter;lower limb;male;medical history;middle aged;muscle rigidity;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;parkinsonism;positron emission tomography;risk factor;serology;slit lamp microscopy;slurred speech;upper limb;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];radiopharmaceutical agent;unclassified drug;fluoropropylcarbomethoxylodopropyl nor b tropane f 18,"Ko, P. W.;Kang, K.;Lee, H. W.",2018,01 Nov,http://dx.doi.org/10.1007/s10072-018-3511-2,0,0,
3289,Bis-choline Tetrathiomolybdate as Old Drug in a New Design for Wilson's Disease: Good for Brain and Liver?,,article;brain;liver;Wilson disease;choline tetrathiomolybdate,"Stremmel, W.",2018,,http://dx.doi.org/10.1002/hep.30130,0,0,
3290,Wilson disease - a case report,"Wilson disease (hepatolenticular degeneration) is due to a genetic abnormality inherited in an autosomal recessive manner that leads to impairment of cellular copper transport. The clinical manifestations of Wilson disease are predominantly hepatic, neurologic, and psychiatric, with many patients having a combination of symptoms. Regardless of the clinical manifestations present initially, patients often develop other clinical manifestations as the disease progresses. Behavioral and psychiatric symptoms are more common in patients with neurologic involvement than in patients with hepatic involvement. However, behavioral and psychiatric symptoms due to Wilson disease are often misdiagnosed. This article presents the case of a 23 year old male, presenting with psychiatric symptoms (depressions, insomnia) which progressed despite pshyciatric treatment. After two years he was diagnosed with Wilson disease, confirmed by genetic testing. Copyright © 2018, Editura Medicala. All rights reserved.",ATP7B gene mutation;Psychiatric symptoms;Wilson disease;adult;article;Babinski reflex;blood cell count;brain disease;case report;cataract;clinical article;consciousness disorder;depression/dt [Drug Therapy];dysarthria;dysphagia;electroencephalography;gene mutation;genetic screening;human;insomnia/dt [Drug Therapy];leukopenia;liver disease;lymphocytopenia;male;mental health;nuclear magnetic resonance imaging;paraplegia;schizophrenia/dt [Drug Therapy];splenomegaly;thrombocytopenia;Wilson disease/dt [Drug Therapy];young adult;carbamazepine/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];creatine kinase/ec [Endogenous Compound];folic acid/ec [Endogenous Compound];haloperidol/dt [Drug Therapy];iron/ec [Endogenous Compound];olanzapine/dt [Drug Therapy];penicillamine/dt [Drug Therapy];phenobarbital/dt [Drug Therapy];uric acid/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc acetate/dt [Drug Therapy];slit lamp,"Cozma, S.;Paraschiv, A.;Vacaras, V.",2018,,,0,0,
3291,Study of clinical profile of and treatment response ofWilson disease in a tertiary care center,"IntroductionWilson disease is caused by a defect in the ATP7B gene that results in impaired biliary copper excretion leading to accumulation of copper in several organs, commonly in liver and brain, causing neurologic dysfunction with chronic liver disease. Methods The study was conducted in the Department of Medical Gastroenterology, Govt. Stanley Medical College, Chennai, from October 2017 July 2018. Sixteen patients diagnosed to have Wilson disease were taken into the study. Patients were analysed based on their clinical features at the time of presentation and they were followed up for clinical response to treatment. Results Age distribution was 11-61 years with majority in the age group between 15-30 years. Majority of the patients (68.7%) presented with hepaticmanifestations. Twenty-five percent patients had neuropsychiatric manifestation. Two patients (13%) had both neurological and hepatic manifestations, both of them presented with tremor. Three patients were asymptomatic and was diagnosed on family screening. Nine patients (56%) were born out of consanguineous marriage. Kayser-Fleischer (KF) ring was found in 56% of patients. All patients with neurological features, 2 out of the 3 asymptomatic patients and 3 patients with only hepatic features had KF ring. Ten patients were treated with penicillamine, 2 patients with zinc and 4 patients were treated with zinc and penicilamine. Nine patients noted improvement with chelation therapy in the form of improved LFT and decreased 24-hour urine copper. Two patients with DCLD underwent liver transplantation and did well in post liver transplant follow up. Fifty-six percent had stable disease and 25% deteriorated, now on liver transplantation work up. Conclusion Family screening is important for early diagnosis. Hepatic manifestations were found to be more common. Penicillamine and zinc therapy can effectively treatWilson disease with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end-stage disease.",adolescent;age distribution;case report;chelation therapy;child;clinical article;clinical feature;consanguineous marriage;diagnosis;disease course;drug therapy;early diagnosis;female;follow up;gastroenterology;human;human tissue;liver graft;male;medical school;mental disease;school child;tertiary care center;treatment response;tremor;urine;Wilson disease;penicillamine;zinc;conference abstract,"Joseph, J.",2018,October,http://dx.doi.org/10.1007/s12664-018-0911-4,0,0,
3292,Hepatic manifestations of Wilson's disease: 12-year experience in a Swiss tertiary referral centre,"BACKGROUND AND AIM: Wilson&rsquo;s disease is an inherited disorder of hepatic copper metabolism, leading to the accumulation of copper in the liver as well as the brain, cornea and other organs. Here, we describe the adult cases of hepatic Wilson&rsquo;s disease diagnosed at the Division of Gastroenterology and Hepatology of the University Hospital Lausanne, Switzerland between September 2004 and August 2016. METHOD(S): Clinical manifestations, results of diagnostic tests, management and outcomes of adult patients with hepatic Wilson&rsquo;s disease were assessed based on standardised medical records. In addition, liver histology was reviewed and the lesional patterns were recorded. RESULT(S): Ten new adult cases of hepatic Wilson&rsquo;s disease were diagnosed in our centre between September 2004 and August 2016. Male to female ratio was 1:1 and median age at diagnosis was 26 (range 18&ndash;56) years. Four patients presented with acute liver failure, four with persistently elevated liver function tests, and two with decompensated cirrhosis; none had neurological manifestations. Only one patient had a Kayser-Fleischer corneal ring. Median ceruloplasmin level at diagnosis was 0.13 (range <0.03&ndash;0.30) g/l, median 24-hour urinary copper excretion was 2.8 (range 0.3&ndash;77.3) &mu;mol, and median hepatic copper concentration was 789 (range 284&ndash;1677) &mu;g/g. At least one mutation in the ATP7B gene was identified in eight patients. Allelic frequency of the common H1069Q mutation was 19%. Leipzig score was &ge;5 in all patients. Three patients presenting with acute liver failure and the two with decompensated cirrhosis underwent successful liver transplantation. One patient with acute liver failure recovered under chelation therapy, as predicted by a Dhawan score <11. D-penicillamine was used as first-line chelator treatment, with a subsequent switch to trientine due to adverse effects in three out of six patients. CONCLUSION(S): The clinical presentation of hepatic Wilson&rsquo;s disease is highly variable. Three out of 10 patients were diagnosed at an age >35 years. A high index of suspicion in clinically compatible situations is key.",acute liver failure;adult;adverse drug reaction;article;case report;chelation therapy;clinical article;decompensated liver cirrhosis;diagnosis;excretion;female;gastroenterology;gene expression;gene frequency;gene mutation;histopathology;human;liver function test;liver histology;liver transplantation;male;medical record;protein expression;side effect;Switzerland;tertiary care center;university hospital;Wilson disease;ceruloplasmin;endogenous compound;penicillamine;trientine;Wilson disease protein,"Vieira Barbosa, J.;Fraga, M.;Saldarriaga, J.;Hiroz, P.;Giostra, E.;Sempoux, C.;Ferenci, P.;Moradpour, D.",2018,17 Dec,,1,1,
3293,Hepatic copper accumulation in a young cat with familial variations in the ATP7B gene,"A 9-month-old intact crossbred female cat was presented with jaundice, intermittent anorexia and lethargy, increased hepatic enzyme activities, and hyperammonemia. Abdominal ultrasound and computed tomographic examinations determined that the liver had a rounded and irregular margin, and histopathological examination identified excessive accumulation of copper hepatocytes in the liver. Concentrations of both blood and urine copper were higher than in healthy cats. The patient responded well to treatment with penicillamine. Clinicopathological abnormalities and clinical signs improved within 2 months, and the patient was alive for >9 months after starting treatment. Genetic examination determined that the patient and its littermate had a single-nucleotide variation (SNV, p. T1297R) that impaired the function of the ATP7B gene product; the gene that is mutated in patients with Wilson's disease (WD). Hepatic copper accumulation was believed to be associated with the SNV of the ATP7B gene, and the patient had a genetic disorder of copper metabolism equivalent to WD in humans. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.",gene mutation;penicillamine;primary copper-associated hepatopathy;Wilson's disease;adult;animal experiment;animal model;animal tissue;anorexia;article;congenital malformation;controlled study;copper metabolism;enzyme activity;female;genetic susceptibility;histopathology;hyperammonemia;jaundice;kitten;lethargy;liver disease;nonhuman;protein function;queen (cat);single nucleotide polymorphism;ultrasound;urine;Wilson disease;endogenous compound;liver enzyme;Wilson disease protein,"Asada, H.;Kojima, M.;Nagahara, T.;Goto-Koshino, Y.;Chambers, J. K.;Nakagawa, T.;Yokoyama, N.;Uchida, K.;Tsujimoto, H.;Ohno, K.",2018,,http://dx.doi.org/10.1111/jvim.15399,0,0,
3294,Pediatric case series of Wilson's disease,"Wilson's disease in children has a varied presentation and may be difficult to diagnose. At the Indira Gandhi Medical College, Shimla, from 2010 to 2015, three children in the age group of 9-11 years presented with hepatic, neurological and neuropsychiatric manifestations. Investigations in all three cases revealed defects in the copper metabolism consistent with those of Wilson's disease. Therefore, this disease should be strongly suspected in children presenting with hepatic and neuropsychiatric symptoms as it is potentially curable. Copyright © 2018 Sir Ganga Ram Hospital",alanine aminotransferase blood level;article;aspartate aminotransferase blood level;behavior change;bilirubin blood level;body position;case report;chelation therapy;child;clinical article;digital clubbing;duodenum ulcer;dysarthria;dystonia;echography;esophagogastroduodenoscopy;esophagus varices;eye disease;face muscle;female;follow up;foot edema;hematemesis;hemolytic anemia;hepatitis;human;jaundice;liver cirrhosis;liver disease;liver function;liver function test;male;muscle spasm;neuropsychiatry;nuclear magnetic resonance imaging;pigment epithelium;portal hypertension;priority journal;school child;splenomegaly;stomach distension;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];liver enzyme/cb [Drug Combination];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];kayser fleischer ring;risus sardonicus,"Nair, P.",2018,November - December,http://dx.doi.org/10.1016/j.cmrp.2018.09.001,0,0,
3295,Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease,"Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, leading to copper accumulation in the liver and brain. Excess copper inhibits S-adenosyl-L-homocysteine hydrolase, leading to variable WD phenotypes from widespread alterations in DNA methylation and gene expression. Previously, we demonstrated that maternal choline supplementation in the Jackson toxic milk (tx-j) mouse model of WD corrected higher thioredoxin 1 (TNX1) transcript levels in fetal liver. Here, we investigated the effect of maternal choline supplementation on genome-wide DNA methylation patterns in tx-j fetal liver by whole-genome bisulfite sequencing (WGBS). Tx-j Atp7b genotype-dependent differences in DNA methylation were corrected by choline for genes including, but not exclusive to, oxidative stress pathways. To examine phenotypic effects of postnatal choline supplementation, tx-j mice were randomized to one of six treatment groups: with or without maternal and/or continued choline supplementation, and with or without copper chelation with penicillamine (PCA) treatment. Hepatic transcript levels of TXN1 and peroxiredoxin 1 (Prdx1) were significantly higher in mice receiving maternal and continued choline with or without PCA treatment compared to untreated mice. A WGBS comparison of human WD liver and tx-j mouse liver demonstrated a significant overlap of differentially methylated genes associated with ATP7B deficiency. Further, eight genes in the thioredoxin (TXN) pathway were differentially methylated in human WD liver samples. In summary, Atp7b deficiency and choline supplementation have a genome-wide impact, including on TXN system-related genes, in tx-j mice. These findings could explain the variability of WD phenotype and suggest new complementary treatment options for WD. Copyright © The Author(s) 2018. Published by Oxford University Press. All rights reserved.",animal cell;animal experiment;animal model;animal tissue;apoptosis;article;cell growth;chelation;controlled study;diet;diet supplementation;diet therapy;disulfide bond;DNA methylation;DNA synthesis;enzyme linked immunosorbent assay;epigenetics;female;fetus liver;gene expression;gene expression system;gene interaction;genetic transcription;genotype;hepatic stellate cell;human;liver;liver biopsy;liver histology;male;microscopy;missense mutation;mouse;nonhuman;oxidative stress;phenotype;priority journal;promoter region;protein isolation;real time polymerase chain reaction;RNA isolation;RNA sequence;sex difference;transcription initiation site;Wilson disease;alanine aminotransferase/ec [Endogenous Compound];choline;copper/ec [Endogenous Compound];DNA (cytosine 5) methyltransferase 1/ec [Endogenous Compound];iron/ec [Endogenous Compound];liver protein/ec [Endogenous Compound];penicillamine/ec [Endogenous Compound];peroxiredoxin 1/ec [Endogenous Compound];reactive oxygen metabolite/ec [Endogenous Compound];thioredoxin/ec [Endogenous Compound];thioredoxin 1/ec [Endogenous Compound];transcriptome/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound],"Mordaunt, C. E.;Shibata, N. M.;Kieffer, D. A.;Czlonkowska, A.;Litwin, T.;Weiss, K. H.;Gotthardt, D. N.;Olson, K.;Wei, D.;Cooper, S.;Wan, Y. J. Y.;Ali, M. R.;LaSalle, J. M.;Medici, V.",2018,01 Nov,http://dx.doi.org/10.1093/hmg/ddy262,0,0,
3296,Trace element provision in parenteral nutrition in children: One size does not fit all,"Routine administration of trace elements is recognised as a standard of care in children requiring parenteral nutrition. However, there is a lack of global consensus regarding trace elements provision and dosing in pediatric parenteral nutrition. This review provides an overview of available evidence regarding trace elements supply and posology in parenteral nutrition in neonates and children. Trace elements provision in children should be tailored to the weight and clinical condition of the child with emphasis on those at risk of toxicity or deficiency. Based on current evidence, there is a need to review the formulation of commercial solutions that contain multiple-trace elements and to enable individual trace elements additives to be available for specific indications. Literature supports the removal of chromium provision whereas manganese and molybdenum supplementation are debated. Preterm neonates may have higher parenteral requirements in iodine, selenium and copper than previously recommended. There is growing support for the routine provision of iron in long-term parenteral nutrition. Further studies on trace elements contamination of parenteral nutrition solutions are needed for a range of trace elements. Copyright © 2018 by the authors. Licensee MDPI, Basel, Switzerland.",Children;Parenteral nutrition;Preterm infants;Trace elements;age;bibliographic database;body weight;bone strength;burn patient;child;clinical feature;copper deficiency;critically ill patient;diarrhea;disorders of higher cerebral function;dose calculation;drug dose;gastrointestinal disease;glomerulus filtration rate;human;hypothyroidism;inflammatory bowel disease;iodine deficiency;iron deficiency;kidney failure;liver dysfunction;metabolic disorder;newborn;nuclear magnetic resonance;nutrition;osteopenia;oxidative stress;pediatric patient;practice guideline;prematurity;randomized controlled trial (topic);review;risk factor;skin defect;Wilson disease;zinc deficiency;chromium;copper;ferric carboxymaltose;ferritin/ec [Endogenous Compound];fluoride;iodine;iron;iron dextran;manganese;molybdenum;selenium;superoxide dismutase/ec [Endogenous Compound];trace element;zinc,"Zemrani, B.;McCallum, Z.;Bines, J. E.",2018,November,http://dx.doi.org/10.3390/nu10111819,0,0,
3297,Recovery of severe acute liver failure without transplantation in patients with Wilson disease,"Wilson disease (WD) is a disorder of copper metabolism that leads to liver cirrhosis. WD patients with a NWIS > 11 should receive LT; however, we encountered 2 WD patients with an NWIS > 11 who recovered from ALF without LT. The present report aimed to analyze cases of WD patients with a high NWIS who recovered from severe ALF and to discuss the clinical manifestations of the patients and the effects of treatments, including zinc (Zn) therapy, chelator therapy, PE, CHDF, and LT. We retrospectively evaluated the medical records of five patients (male, 2; female, 3) diagnosed with WD along with severe ALF. In cases 1, 2, and 3, complete recovery from ALF was noted without LT. In case 4, initial recovery from ALF was noted without LT; however, ALF worsened owing to bleeding from the esophageal varix. Thus, the patient eventually needed LT. In case 5, recovery from ALF was noted with LT. All cases, except case 2, showed ALF with maximum PELD/MELD scores >=26 and NWISs >= 11, and had indications for LT. In cases of severe ALF with grade I or II encephalopathy, we recommend evaluations of the effects of Zn and chelator treatments while preparing for LT, as the condition may not improve without LT, and pediatricians or physicians can ask transplant surgeons to perform LT urgently if required. Copyright © 2018 Wiley Periodicals, Inc.",acute liver failure;liver transplantation;new Wilson index;plasma exchange;Wilson disease;zinc therapy;abdominal radiography;abdominal tenderness/di [Diagnosis];acute liver failure/di [Diagnosis];acute liver failure/dt [Drug Therapy];adolescent;agranulocytosis/di [Diagnosis];anemia/di [Diagnosis];article;ascites/di [Diagnosis];bleeding/di [Diagnosis];blood transfusion;case report;ceruloplasmin blood level;child;clinical article;copper blood level;disease severity;echography;esophagus varices/di [Diagnosis];female;fever/di [Diagnosis];hemoglobin blood level;hemolysis/di [Diagnosis];hospital admission;hospital discharge;hospitalization;human;hyperbilirubinemia/di [Diagnosis];jaundice/di [Diagnosis];liver atrophy/di [Diagnosis];liver cirrhosis/di [Diagnosis];liver failure/di [Diagnosis];male;medical record review;pancytopenia/di [Diagnosis];patient referral;patient transport;prothrombin time;retrospective study;school child;splenomegaly/di [Diagnosis];urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];fresh frozen plasma/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Kido, J.;Matsumoto, S.;Sakamoto, R.;Mitsubuchi, H.;Inomata, Y.;Nakamura, K.",2018,December,http://dx.doi.org/10.1111/petr.13292,0,0,
3298,Wilson's disease: A 2017 update,"Wilson's disease (WD) is characterised by a deleterious accumulation of copper in the liver and brain. It is one of those rare genetic disorders that benefits from effective and lifelong treatments that have dramatically transformed the prognosis of the disease. In Europe, its clinical prevalence is estimated at between 1.2 and 2/100,000 but the genetic prevalence is higher, at around 1/7000. Incomplete penetrance of the gene or the presence of modifier genes may account for the difference between the calculated genetic prevalence and the number of patients diagnosed with WD. The clinical spectrum of WD is broader as expected with mild clinical presentations and late onset of the disease after the age of 40 in 6% of patients. WD is usually suspected when ceruloplasmin and serum copper levels are low and 24 h urinary copper excretion is elevated. Recently, a major diagnostic advance was achieved with implementation of the direct assay of ""free copper"" or exchangeable copper (CuEXC). The relative exchangeable copper (REC) that corresponds to the ratio between CuEXC and total serum copper enables a diagnosis of WD with high sensitivity and specificity when REC > 18.5%. Moreover, CuEXC values at diagnosis are a marker of extrahepatic involvement and its severity. A value of >2.08 mumol/L is suggestive of corneal and brain involvement (Se = 86%, Sp = 94%), and the disease will be more clinically and radiologically severe as values rise. The use of FibroScan<sup></sup> is becoming more widespread to assess liver stiffness measurements in WD patients. 6.6 kPa is considered to be a threshold value between mild and moderate fibrosis, whereas a value higher than 8.4 is indicative of severe fibrosis. More studies are now necessary to confirm the usefulness of Fibroscan<sup></sup> in managing chronic therapy for WD patients. Treatment of this disease is based on an initial active and prolonged chelating phase (with D-Penicillamine or Trientine) followed by maintenance with Trientine or zinc salt. The two major problems that may be encountered are neurological worsening during the initial phase and non-compliance with treatment during maintenance therapy. Liver transplantation is the recommended therapeutic option in WD with acute liver failure or end-stage liver cirrhosis; its indication should be considered when neurological status deteriorates rapidly despite effective chelation. Regular clinical, biological and liver ultrasound follow-up is essential to evaluate efficacy, tolerance and treatment compliance, but also to detect the onset of hepatocellular carcinoma on a cirrhotic liver. There are hopes in the near future with the introduction of a new chelator and inhibitor of copper absorption, tetrathiomolybdate (TTM) and the development of gene therapy. Copyright © 2018 Elsevier Masson SAS",atp7b;Copper;Exchangeable copper;Liver transplantation;Wilson's disease;acute liver failure;clinical assessment;clinical effectiveness;clinical evaluation;clinical feature;disease severity;echography;end stage liver disease;follow up;gene therapy;hepatocyte transplantation;human;liver cirrhosis;liver fibrosis;liver stiffness;maintenance therapy;next generation sequencing;non invasive procedure;nonhuman;nuclear magnetic resonance imaging;pathophysiology;prevalence;sensitivity and specificity;short survey;treatment refusal;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/dt [Drug Therapy];zinc derivative;elastograph,"Poujois, A.;Woimant, F.",2018,December,http://dx.doi.org/10.1016/j.clinre.2018.03.007,0,0,
3299,Copper-chelators are also relatively potent zinc chelators,"Zinc (Zn) is an essential metal that is involved in numerous physiological processes. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in protein and DNA synthesis, cell division, wound healing and immunity. Zinc deficiency is characterized by growth retardation, loss of appetite, suppressed immune function, diabetes, etc. One of the causes of zinc deficiency can be the long-life use of metal chelators which are mostly non-selective. Such example are copper-chelators used in rare inherited disorder resulting in body copper excess - Wilson's disease. The aim of this work was to study possible ability of D-penicillamine, trientine and ammonium tetrathiomolybdate (ATM) to bind zinc by a spectrophotometric method based on the competition between the tested compound and dithizone as an indicator. Various physiologically relevant pH levels ranging from 4.5 to 7.5 were tested. compound and dithizone as an indicator. Various physiologically relevant pH levels ranging from 4.5 to 7.5 were tested. All the compounds shown the non-selectivity for copper and the capacity to bind zinc. Experiments showed that the most potent Zn chelator was trientine. It can bind approximately 65% of Zn when is mixed with zinc ions in the molar ratio of 1:1 at pH 7.5. D-penicillamine and ATM showed lower chelating capacity. Surprisingly all of the tested compound showed higher capacity to form a complex with Zn ion in comparison with ability of D-penicillamine to chelate Cu ions. Clinically used copper-chelators as well ATM are also relatively potent zinc chelators and hence they long term use can possibly result in toxicity associated with zinc deficiency.",chelation;competition;controlled study;drug combination;spectroscopy;Wilson disease;zinc deficiency;chelate;copper ion;dithizone;penicillamine;tetrathiomolybdate ammonium;trientine;unclassified drug;zinc;zinc ion;conference abstract,"Tvrdy, V.;Karlickova, J.;Hanuscinova, L.;Mladenka, P.",2018,May,http://dx.doi.org/10.2478/intox-2018-0006,0,0,
3300,"Wilson disease in children: A patient perspective on diagnosis, treatment and adherence and monitoring","Wilson Disease (WD) is a rare autosomal recessive disease of copper transport that may present in childhood with a wide spectrum of presentations (hepatic, neurologic and/or psychiatric). Treatment requires life-long adherence with diet and medical therapy. The aims of the study were to assess patient reported symptoms at diagnosis and treatment. An electronic survey was distributed to 877 WD patients in the WD Association patient network. Of the 124 respondents, 34 were <21yo: 10 were < 10yo and 65% were female. Most patients were from North America (79%) and had private insurance (65%). The diagnosis of WD was established before the age of 1 y in two, between 1-5 y in 9, between 6-10 y in 12 and between 11-19 y in 11 cases. Presenting symptoms were primarily hepatic (56%), neurologic (21%) and psychiatric (9%). 6/7 patients with neurologic disease had concurrent liver involvement and in 2 cases was reported as severe liver disease. All patients with psychiatric presentation had liver disease. Patients currently report being treated with trientine (44%), zinc salts (29%), D-penicillamine (1 patient) and combination therapy of zinc and chelator (24%). Only about one third, 32%, remained on the same treatment they initially started on for their WD. In 41% medications were changed once and in another 27% treatment changed more than once. With respect to treatment adherence, 59% reported never missing a dose, 20% once a week and 21% reported missing doses more than twice a week, mostly the afternoon dose (82%). The most common cause for non-adherence was forgetfullness (74%), though 41% reported medication side effects as the reason for missing doses. Medications were obtained at local pharmacy (44%), by mail order (29%) and at a specialty pharmacy (21%) and other (6%). Of interest, 53% reported that the pharmacy did not have the medication available on time and 38% had challenges with insurance approval for their medication. The median monthly out of pocket expense was 25-50 $. Adherence to a strict low copper diet was reported in 56%, 36% were somewhat adherent while 8% reported not restricting diet at all. Medical follow up soley was by a gastroenterologist in 26%, by a hepatologist in 21% and by primary care physiciansin in 15% and a combination of specilaists in 48%. For monitoring therapy, blood tests were performed every 3 months in 44% and every 6 months in another 44% and annually in 12%. The majority (68%) were seen by their MD at least every 6 months. Quality of life was reported to affected WD patients in 62%. Conclusion(s): WD diagnosed in childhood may present mostly with hepatic symptoms, however nerologic or psychiatric symptoms were also present at diagnosis in the minority. Medical therapies changed from the initial therapy in the majority of patients, and reasons for this need to be explored. Medication adherence was a challenge for about 40% of patients due to patient and non-patient issues. Therefore improving medication adherence needs to address patient forgetfullness, side effects of treatment and medication access.",adverse drug reaction;child;diagnosis;diet;drug combination;drug therapy;female;follow up;gastroenterologist;hepatologist;human;infant;insurance;major clinical study;male;medication compliance;mental disease;monitoring;North America;outcome assessment;pharmacy;primary medical care;quality of life;side effect;Wilson disease;penicillamine;trientine;zinc;zinc derivative;conference abstract,"Miloh, T.;Schilsky, S.;Graper, M.;Gonzalez-Peralta, R.;Schilsky, M.",2018,November,http://dx.doi.org/10.1097/MPG.0000000000002164,0,0,
3301,Chelating principles in Menkes and Wilson diseases: Choosing the right compounds in the right combinations at the right time,"Dysregulation of copper homeostasis in humans is primarily found in two genetic diseases of copper transport, Menkes and Wilson diseases, which show symptoms of copper deficiency or overload, respectively. However, both diseases are copper storage disorders despite completely opposite clinical pictures. Clinically, Menkes disease is characterized by copper deficiency secondary to poor loading of copper-requiring enzymes although sufficient body copper. Copper accumulates in non-hepatic tissues, but is deficient in blood, liver, and brain. In contrast, Wilson disease is characterized by symptoms of copper toxicity secondary to accumulation of copper in several organs most notably brain and liver, and a saturated blood copper pool. It is a challenge to correct copper dyshomeostasis in either disease though copper depletion in Menkes disease is most challenging. Both diseases are caused by defective copper export from distinct cells, and we seek to give new angles and guidelines to improve treatment of these two complementary diseases. Therapy of Menkes disease with copper-histidine, thiocarbamate, nitrilotriacetate or lipoic acid is discussed. In Wilson disease combination of a hydrophilic chelator e.g. trientine or dimercaptosuccinate with a brain shuttle e.g. thiomolybdate or lipoate, is discussed. New chelating principles for copper removal or delivery are outlined. Copyright © 2018",Chelation;Copper;Histidine;Ionophores;Menkes disease;Wilson disease;bioaccumulation;brain;copper blood level;copper deficiency;homeostasis;human;liver;Menkes syndrome/dt [Drug Therapy];review;symptomatology;Wilson disease/dt [Drug Therapy];copper/to [Drug Toxicity];copper complex/dt [Drug Therapy];histidine derivative/dt [Drug Therapy];nitrilotriacetic acid/dt [Drug Therapy];succimer/dt [Drug Therapy];thiocarbamic acid/dt [Drug Therapy];thioctic acid/dt [Drug Therapy];thiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy],"Horn, N.;Moller, L. B.;Nurchi, V. M.;Aaseth, J.",2019,January,http://dx.doi.org/10.1016/j.jinorgbio.2018.10.009,0,0,
3302,Quantitative trace element mapping in liver tissue from patients with Wilson`s disease determined by micro X-ray fluorescence,"Aims: of this investigation were to quantify copper (Cu), iron (Fe) and zinc (Zn) along with sulphur (S) and phosphorus (P) in hepatocytes and connective tissue in liver section from patients with Wilson's disease (WD) by micro Synchrotron X-ray fluorescence (mu-SRXRF). Secondly to establish two-dimensional mu-SRXRF element mappings for comparison with histologically prepared slices, and thirdly to assess whether elemental distributions are associated. Method(s): Archival liver tissues from twelve patients with end-stage cirrhosis or fulminant WD were investigated. Mutations in ATP7B have been classified before. For control seven archived normal liver tissues were investigated. mu-SRXRF measurements were performed at the DORIS III storage ring at HASYLAB/DESY (Hamburg, Germany). Two-dimensional element distribution were compared with histologically prepared slices about 20-30 mum apart from those investigated by mu-SRXRF. Result(s): Elementary copper (Cu) could be demonstrated in all investigated liver sections simultaneously with Fe, Zn, P and S. In WD mean Cu was 20 fold increased in hepatocytes and threefold in fibrotic areas in comparison with controls. In regeneration nodules Cu was strikingly inhomogeneous distributed. Cu concentrations measured by mu-SRXRF correlated with those measured by atom absorption spectroscopy. Strong associations in their regional distribution existed between Zn and Cu or Fe and S. Moreover, differences in Cu/S were found between hepatocytes and fibrotic areas. An increase of Fe could only be documented in hepatocytes compared to fibrotic areas. With a beam size of 15 x 15 mum two-dimensional distributions of these elements are morphologically comparable with histological section with a magnification of about 25x optic microscope. Conclusion(s): mu-SRXRF investigations are a valuable tool for quantifying element concentrations in biological tissues and further provide 2-dimensional information of element distribution and elemental association in a biological tissues, thus speeding up basic knowledge in a synopsis with biological and clinical data. Copyright © 2018",Atomic absorption;Copper;Iron;Phosphorus;Sulphur;Synchrotron X-ray fluorescence;Trace element mapping;Wilson's disease;Zinc;adolescent;adult;article;atomic absorption spectrometry;child;clinical article;concentration (parameters);controlled study;female;gene mutation;histochemistry;human;human cell;human tissue;liver cell;liver cirrhosis;liver slice;liver structure;liver tissue;male;microscopy;middle aged;priority journal;school child;synchrotron radiation;Wilson disease/di [Diagnosis];X ray fluorescence;young adult;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];phosphorus/ec [Endogenous Compound];sulfur/ec [Endogenous Compound];trace element/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc/ec [Endogenous Compound];Atp7b gene,"Osterode, W.;Falkenberg, G.;Ferenci, P.;Wrba, F.",2019,January,http://dx.doi.org/10.1016/j.jtemb.2018.09.007,0,0,
3303,Altered zinc balance in the Atp7b<sup>-/-</sup> mouse reveals a mechanism of copper toxicity in Wilson disease,"Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the ATP7B gene that affects copper transport in the body. ATP7B mutation damages copper transporter function, ultimately resulting in excessive copper accumulation and subsequent toxicity in both the liver and brain. Mechanisms of copper toxicity, however, are not well defined. The Atp7b<sup>-/-</sup> mouse model is well-characterized and presents a hepatic phenotype consistent with WD. In this study, we found that the untreated Atp7b<sup>-/-</sup> mice accumulate approximately 2-fold excess hepatic zinc compared to the wild type. We used targeted transcriptomics and proteomics to analyze the molecular events associated with zinc and copper accumulation in the Atp7b<sup>-/-</sup> mouse liver. Altered gene expression of Zip5 and ZnT1 zinc transporters indicated a transcriptional homeostatic response, while increased copper/zinc ratios associated with high levels of metallothioneins 1 and 2, indicated altered Zn availability in cells. These data suggest that copper toxicity in Wilson disease includes effects on zinc-dependent proteins. Transcriptional network analysis of RNA-seq data reveals an interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors. In the context of previous research, these observations support the hypothesis that mechanisms of copper toxicity include disruption of intracellular zinc distribution in liver cells. The translational significance of this work lies in oral zinc supplementation in treatment for WD, which is thought to mediate protective effects through the induction of metallothionein synthesis in the intestine. This work indicates broader impacts of altered zinc-copper balance in WD, including global transcriptional responses and altered zinc balance in the liver. Copyright © The Royal Society of Chemistry.",animal experiment;animal model;animal tissue;article;controlled study;diet supplementation;female;gene expression;gene expression level;immunodetection;intestine;liver;male;mouse;nonhuman;priority journal;real time polymerase chain reaction;RNA sequence;transcriptomics;Western blotting;wild type;Wilson disease/dt [Drug Therapy];zinc metabolism;aspartate aminotransferase/ec [Endogenous Compound];carbonate dehydratase II/ec [Endogenous Compound];carbonate dehydratase III/ec [Endogenous Compound];copper/ec [Endogenous Compound];copper zinc superoxide dismutase/ec [Endogenous Compound];glutathione transferase P1/ec [Endogenous Compound];glyceraldehyde 3 phosphate/ec [Endogenous Compound];hemoglobin alpha chain/ec [Endogenous Compound];hemoglobin beta chain/ec [Endogenous Compound];iron/ec [Endogenous Compound];metallothionein/ec [Endogenous Compound];metallothionein II/ec [Endogenous Compound];myoglobin/ec [Endogenous Compound];regucalcin/ec [Endogenous Compound];unclassified drug;zinc/dt [Drug Therapy];zinc/po [Oral Drug Administration];zinc transporter Zip1/ec [Endogenous Compound];zinc transporter zip10/ec [Endogenous Compound];zinc transporter ZIP13/ec [Endogenous Compound];zinc transporter Zip14/ec [Endogenous Compound];zinc transporter ZIP4/ec [Endogenous Compound];zinc transporter ZIP5/ec [Endogenous Compound];zinc transporter ZIP7/ec [Endogenous Compound];zinc transporter ZIP8/ec [Endogenous Compound];zinc transporter ZIP9/ec [Endogenous Compound];zinc transporter ZNT1/ec [Endogenous Compound],"Meacham, K. A.;Cortes, M. P.;Wiggins, E. M.;Maass, A.;Latorre, M.;Ralle, M.;Burkhead, J. L.",2018,November,http://dx.doi.org/10.1039/c8mt00199e,0,0,
3304,Value of serum zinc in diagnosing and assessing severity of liver disease in children with wilson disease,"Objectives: Wilson disease (WD) is a rare inborn error of copper metabolism with diverse manifestations. There has been no study of zinc (Zn), the copper's antagonist, in WD diagnosis and severity so far. Our aims were to evaluate serum Zn in WD and its correlation with the disease severity score (revised WD index). Although the ATP7B mutation analysis is highly accurate for WD diagnosis, it may not be readily available in a resource-limiting setting. We proposed a disease diagnostic score (Proposed WD diagnostic score) which incorporates serum Zn. Method(s): Medical records of WD and non-WD children seen at King's College Hospital from 2005 to 2015 were reviewed for the selected parameters using the Proposed WD diagnostic score. Available serum Zn data in WD children before disease diagnosis and the calculated severity score were statistically analyzed. Diagnostic values of the Proposed WD diagnostic score were evaluated. Result(s): Serum Zn level was significantly lower in 8 WD-acute liver failure (ALF) (5.8 [4.1-8.3] mumol/L) compared to 18 WD-non-ALF (13.5 [6.1-22.2] mumol/L) and 9 ALF from indeterminate cause (9.8 [7.0-12.1] mumol/L) (P < 0.001). Serum Zn significantly correlated with the revised WD index (r = -0.554, P = 0.004). The Proposed WD diagnostic score that included serum Zn level as 1 of the parameters had sensitivity and specificity of 87% and 99.2%, respectively. Conclusion(s): Serum Zn is a novel parameter for diagnosis and correlates with severity of WD. The Proposed WD diagnostic score is useful while awaiting ATP7B mutation analysis. Copyright © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.",atp7b;Liver copper;Penicillamine challenge test;Zinc;abdominal distension;acute liver failure;acute stress;alkaline phosphatase blood level;article;ascites;autoimmune hepatitis;ceruloplasmin blood level;childhood disease/di [Diagnosis];chronic hepatitis;clinical article;diagnostic accuracy;diagnostic test accuracy study;diagnostic value;disease severity assessment;England;false negative result;female;foot edema;gene mutation;hematemesis;histopathology;human;incidental finding;jaundice;laboratory test;liver disease;liver function test;liver ischemia;male;medical record review;nonalcoholic fatty liver;priority journal;provocation test;receiver operating characteristic;sensitivity and specificity;splenomegaly;toxic hepatitis;Wilson disease/di [Diagnosis];zinc blood level;ceruloplasmin/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc/ec [Endogenous Compound],"Sintusek, P.;Kyrana, E.;Dhawan, A.",2018,,http://dx.doi.org/10.1097/MPG0000000000002007,0,0,
3305,Characteristics and prevalence of Wilson's disease: A 2013 observational population-based study in France,"Background and aims: Only a few epidemiological studies on the incidence and prevalence of Wilson's disease (WD) have been performed to date, and the results vary widely according to the reports. The aim of the study was to investigate the prevalence, ambulatory care and treatments of patients with WD in France. Method(s): Among the 58 million general health scheme beneficiaries (86% of the French population), people managed for WD in 2013 were identified using hospitalisation diagnosis in 2011-2013 or specific long-term disease status with a 100% reimbursement for specific healthcare in 2013. Data were derived from the Sniiram (National Health Insurance Information System database). Prevalence by age and sex were calculated. Result(s): In 2013, 906 prevalent cases were identified, yielding a crude prevalence of 1.5 cases per 100,000; 1.65 per 100,000 in males and 1.44 per 100,000 in females. This prevalence is comparable to that reported in other population-based studies in European countries and to a study using a similar method. Almost 40% of patients were treated by D-penicillamine and 14.3% were treated by zinc acetate. Trientine, delivered on a compassionate basis, was not available in the reimbursement database. In 2013, 1.3% of patients underwent liver transplantation and 4% had already undergone liver transplantation in previous years. Fifteen per cent of patients received antidepressants, a higher rate than in general population. Conclusion(s): This is the first French population-based epidemiological study of WD in a comprehensive population based on administrative data and constitutes an important step to understand the impact of WD and to study quality of care. Copyright © 2017 Elsevier Masson SAS",D-penicillamine;Epidemiology;Geographical distribution;Healthcare use;Wilson's disease;Zinc;adolescent;adult;aged;ambulatory care;article;child;chronic disease/su [Surgery];epidemiological data;Europe;female;France;Frenchman;groups by age and sex;hospitalization;human;infant;liver transplantation;major clinical study;male;medical information system;middle aged;national health insurance;observational study;population research;preschool child;prevalence;reimbursement;school child;very elderly;Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/su [Surgery];young adult;antidepressant agent;penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Poujois, A.;Woimant, F.;Samson, S.;Chaine, P.;Girardot-Tinant, N.;Tuppin, P.",2018,February,http://dx.doi.org/10.1016/j.clinre.2017.05.011,0,1,2
3306,Low serum alkaline phosphatase activity in a teenage girl,"Background: Hypophosphatasia (HPP) is a rare and genetic disorder that affects bone mineralization. There are currently six forms of HPP that range in age of onset and severity: perinatal (lethal), perinatal benign, infantile, childhood, adult and odontohypophosphatasia. Perinatal HPP is the most severe and results in death in utero, whereas adult HPP is milder and presents with pain and osteomalacia. HPP is caused by mutations of the ALPL gene encoding tissue-non-specific alkaline phosphatase. One of the cardinal features of HPP is a low serum alkaline phosphatase (ALP) activity. Recognition of HPP and differentiation from other causes of ALP activity is required for proper diagnosis and treatment. Here we present a clinical case of a 17-year-old girl who presented with fatigue at her annual medical exam. Results from an external laboratory showed low daytime cortisol concentration. She was referred to endocrinology for chronic fatigue and possible adrenal insufficiency per her father's request. Family history was notable for hypothyroidism and chronic fatigue syndrome. Her medical history was notable for the presence of anti-TPO antibodies below the diagnostic threshold and a normal TSH. Of note she was taking folate, vitamin B12, and multi-vitamins. During her initial workup laboratory results were notable for low ALP activity (24 units/L; reference interval 55-140 unit/L). Low ALP activity can be due to Wilson's disease, hypophosphatasia, pernicious anemia and severe hypothyroidism. Magnesium and zinc deficiencies were once sources of falsely low ALP measurements but current assay formulations incorporate magnesium and zinc to circumvent this issue. Method(s): : In order to differentiate the cause of her low serum ALP activity, new samples were collected and ALP activity repeated. In addition ALP-isoenzyme analysis, sequencing of the ATP7B gene, ceruloplasmin, vitamin B6 (P5P) and urine phosphoethanolamine quantification were also performed. Result(s): The repeat analysis of the patient's serum ALP activity was 23 units/L. ALP-isoenzyme analysis was not possible due to insufficient ALP activity. Initial results showed elevated concentration of vitamin B12 and normal thyroid function, eliminating pernicious anemia and hypothyroidism from the differential. The patient's ceruloplasmin concentration was quantified as 16.5 mg/dL (reference interval 16- 45 mg/dL) prompting further evaluation for Wilson's disease via sequencing of the ATP7B gene which did not reveal any deleterious mutations. Vitamin B6 and PEA concentrations were 95 mug/L; 5-50 mug/L) and (80 mmol/mg Cr; <88 mmol/mg Cr), respectively, values consistent with hypophosphatasia. Conclusion(s): Due to the absence of bone abnormalities and impaired growth, HPP was initially considered unlikely; however, the combination of low ALP activity and high vitamin B6 and PEA are consistent with a diagnosis of hypophosphatasia. Her clinical features suggest a mild form of childhood or adult HPP. This case was complicated by ceruloplasmin concentration at the lower limit of the reference interval. The diagnosis was also complicated by a later admission that the patient was receiving cortisol from her father in order to treat her fatigue. The family was advised to stop giving exogenous cortisol and the patient successfully tapered off without any signs of an acute adrenal crisis. The family declined genetic testing of the ALPL gene.",adolescence;adolescent;adrenal insufficiency;alkaline phosphatase blood level;bone;case report;child;childhood;chronic fatigue syndrome;clinical article;clinical feature;congenital malformation;diagnosis;differentiation;drug formulation;drug therapy;endocrinology;family history;father;female;gene mutation;genetic screening;girl;human;human tissue;hypophosphatasia;hypothyroidism;infant;magnesium deficiency;male;pernicious anemia;quantitative analysis;reference value;thyroid function;urine;Wilson disease;zinc deficiency;alkaline phosphatase;alkaline phosphatase isoenzyme;ceruloplasmin;chromium;cyanocobalamin;endogenous compound;folic acid;hydrocortisone;magnesium;phosphoethanolamine;pyridoxine;thyroid peroxidase antibody;thyrotropin;Wilson disease protein;zinc;conference abstract,"Shajani-Yi, Z.;Casella, S. J.;Cervinski, M. A.",2017,,,0,0,
3307,Update on the Diagnosis and Management of Wilson Disease,"Purpose of Review: Exciting developments relating to Wilson disease (WD) have taken place with respect to both basic biological and clinical research. This review critically examines some of these findings and considers their implications for current thinking about WD. It is not a comprehensive review of WD as a clinical disorder. Recent Findings: The structure of the gene product of ATP7B, abnormal in WD, is being worked out in detail, along with a broader description of how the protein ATP7B (Wilson ATPase) functions in cells including enterocytes, not only in relation to copper disposition but also to lipid synthesis. Recent population studies raise the possibility that WD displays incomplete penetrance. Innovative screening techniques may increase ascertainment. New strategies for diagnosing and treating WD are being developed. Several disorders have been identified which might qualify as WD-mimics. Summary: WD can be difficult to diagnose and treat. Insights from its pathobiology are providing new options for managing WD. Copyright © 2018, Springer Science+Business Media, LLC, part of Springer Nature.","atp7b;Bis-choline tetrathiomolybdate;Copper;d-penicillamine;Drug-pricing;Hepatic;Hepatolenticular degeneration;Methanobactin;Neurological;Psychiatric;Trientine;Wilson ATPase;Wilson disease;Zinc salts;enzyme activity;enzyme structure;gene replacement therapy;health care access;human;intestine;lipid metabolism;mental disease;nonhuman;review;screening;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];4 phenylbutyric acid/dt [Drug Therapy];bacterial protein/dt [Drug Therapy];choline tetrathiomolybdate/dt [Drug Therapy];copper/ec [Endogenous Compound];curcumin/dt [Drug Therapy];n (2,2,2 trifluoroethyl) n [4 (2,2,2 trifluoro 1 hydroxy 1 trifluoromethylethyl)phenyl]benzenesulfonamide/dt [Drug Therapy];n (2,2,2 trifluoroethyl) n [4 (2,2,2 trifluoro 1 hydroxy 1 trifluoromethylethyl)phenyl]benzenesulfonamide/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];unclassified drug;Wilson disease protein/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc derivative/dt [Drug Therapy];methanobactin/dt [Drug Therapy]","Roberts, E. A.",2018,01 Dec,http://dx.doi.org/10.1007/s11894-018-0660-7,0,0,
3308,An Unusual Dystonic Manifestation in Wilson's Disease,,Dystonia;Wilson's disease;adult;arm movement;case report;central nervous system;clinical article;disease exacerbation;dystonic disorder;female;human;neurologic disease;note;priority journal;Wilson disease/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc acetate/dt [Drug Therapy],"Overdijk, M. J.;de Bie, R. M. A.;Berendse, H. W.;van Rootselaar, A. F.",2018,September/October,http://dx.doi.org/10.1002/mdc3.12639,0,0,
3309,Movement Disorders and Neurometabolic Diseases,"Many inherited metabolic diseases or inborn errors of metabolism (IEM) cause movement disorders in children. This review focuses on chorea, dystonia, myoclonus, tremor, and parkinsonism. Broad neurometabolic categories commonly responsible for pediatric movement disorders include mitochondrial cytopathies, organic acidemias, mineral metabolism and transport disorders, neurotransmitter diseases, purine metabolism abnormalities, lipid storage conditions, and creatine metabolism dysfunction. Each movement disorder can be caused by many IEM and several of them can cause multiple movement abnormalities. Dietary modifications, medications, and increasingly specific therapy can improve outcomes in children with movement disorders caused by IEM. Recognition and characterization of secondary movement disorders in children facilitate their management and diagnosis, and possible treatment of an underlying IEM. Copyright © 2018 Elsevier Inc.",acidemia;article;biotinidase deficiency/dt [Drug Therapy];chorea/co [Complication];chorea/et [Etiology];diet therapy;disease association;disorders of mitochondrial functions;dyskinesia/dt [Drug Therapy];dystonia/co [Complication];dystonia/dt [Drug Therapy];dystonia/et [Etiology];early diagnosis;gene mutation;human;inborn error of metabolism;Leigh disease/di [Diagnosis];Leigh disease/et [Etiology];lipid storage;metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];metabolic disorder/su [Surgery];mineral metabolism;motor dysfunction/co [Complication];motor dysfunction/et [Etiology];myoclonus/co [Complication];myoclonus/dt [Drug Therapy];myoclonus/et [Etiology];neurodegeneration with brain iron accumulation/di [Diagnosis];neurodegeneration with brain iron accumulation/et [Etiology];neurodegeneration with brain iron accumulation/su [Surgery];neurologic disease;outcome assessment;parkinsonism/co [Complication];parkinsonism/et [Etiology];tremor/co [Complication];tremor/et [Etiology];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];amantadine/cb [Drug Combination];amantadine/dt [Drug Therapy];baclofen/dt [Drug Therapy];biotin/dt [Drug Therapy];botulinum toxin A/dt [Drug Therapy];glucose transporter 1/ec [Endogenous Compound];levodopa/cb [Drug Combination];levodopa/dt [Drug Therapy];penicillamine/dt [Drug Therapy];selegiline/cb [Drug Combination];selegiline/dt [Drug Therapy];trientine/dt [Drug Therapy];valproic acid/dt [Drug Therapy];creatine metabolism dysfunction;glucose transporter type 1 deficiency syndrome/di [Diagnosis];glucose transporter type 1 deficiency syndrome/su [Surgery];glutaric aciduria type 1/dt [Drug Therapy];glutaric aciduria type 1/et [Etiology];glutaric aciduria type 1/su [Surgery];neurometabolic disorder;neurotransmitter disease;pediatric neurotransmitter disease/di [Diagnosis];pediatric neurotransmitter disease/et [Etiology];purine metabolism abnormality,"Christensen, C. K.;Walsh, L.",2018,April,http://dx.doi.org/10.1016/j.spen.2018.02.003,0,0,
3310,Dietary copper restriction in Wilson's disease review-article,"Dietary copper restriction has long been considered an important aspect of treatment for Wilson's disease (WD). However, evidence supporting this approach is limited. There are no published randomised controlled trials examining this recommendation due to rarity of the disease and variable presentation. This review summarises current knowledge on the absorption and regulation of copper in humans and its relevance to patients with WD. Studies have demonstrated that as the level of dietary copper increases, the proportion absorbed decreases. This observation implies that 'high copper' foods that WD patients are generally advised to avoid would need to be consumed in large amounts to impact markedly on the quantity absorbed. Dietary copper restriction is unlikely to reduce the amount absorbed significantly and is not only difficult to manage but restricts food groups unnecessarily, detracting from the provision of substrates essential for improving nutritional status in a nutritionally compromised group. Medical management for WD is effective in compliant patients, allowing stabilisation of the liver disease. Based on current evidence, dietary copper restrictions in stable WD patients who are adherent to medical therapy are unnecessary with two food exceptions (shellfish and liver). Copyright © 2017 Macmillan Publishers Limited, part of Springer Nature.",absorption;article;diet restriction;dietary intake;food intake;human;liver;liver disease;nutritional status;patient compliance;regulatory mechanism;shellfish;Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];copper restriction,"Russell, K.;Gillanders, L. K.;Orr, D. W.;Plank, L. D.",2018,01 Mar,http://dx.doi.org/10.1038/s41430-017-0002-0,0,0,
3311,The hidden face of Wilson's disease,"In brief, the classic form of Wilson's disease (WD) is an autosomal-recessive condition with hepatic, neurologic, psychiatric and systemic manifestations. However, the diagnosis should not be excluded because of a family history consistent with autosomal-dominant transmission. The latest next-generation sequencing (NGS) studies have demonstrated a gap between phenotype and genetic prevalences, and also suggest that WD may still be underdiagnosed. In a majority of WD patients, early recognition and appropriate treatment can result in resolution of symptoms and/or improved quality of life. Thus, finding WD in patients aged > 40 years or with thrombocytopenia, hemolytic anemia, unexplained bone pain, amenorrhea, repeated spontaneous abortion or renal lithiasis is of major importance. These symptoms can all be found on their own or in association with mild-to-incapacitating neurological and/or neuropsychiatric manifestations. While brain lesions of the lenticular, midbrain and dentate nuclei are classic, white-matter changes and cortical lesions may also be observed: these are often asymmetrical with frontal lobe predilection and, when extensive, associated with a poor prognosis. These lesions are due mainly to copper deposition, but may also be related to focal accumulation of other metals, such as iron and manganese. A new biological marker called 'relative exchangeable copper' (REC) facilitates diagnosis and familial screening. Patient monitoring is important to ensure treatment adherence, efficacy and tolerability, and to detect rare complications such as copper deficiency induced by chronic copper chelation and hepatocarcinoma in patients with cirrhosis. Currently used treatments are copper chelators and zinc salts. Therapeutic perspectives are liver transplantation, new copper chelators as tetrathiomolybdate, hepatocyte/tissue transfer and gene therapy. Copyright © 2018 Elsevier Masson SAS",Autosomal-recessive condition;Biological marker;Copper biomarkers;Next-generation sequencing;Wilson's disease;acute disease;autosomal recessive inheritance;bone disease;brain malformation;cell transfer;chelation therapy;clinical feature;diagnostic imaging;disease course;endocrine disease;eye disease;gene therapy;genetic analysis;genetic association;hematologic disease;human;kidney disease;late onset disorder;liver transplantation;maintenance therapy;mental disease;neuroimaging;neurologic disease;nonhuman;normal value;nuclear magnetic resonance imaging;onset age;prevalence;review;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];Wilson disease/ep [Epidemiology];Wilson disease/su [Surgery];Wilson disease/th [Therapy];biological marker/ec [Endogenous Compound];chelating agent;copper/ec [Endogenous Compound];iron/ec [Endogenous Compound];manganese/ec [Endogenous Compound];tetrathiomolybdic acid,"Woimant, F.;Djebrani-Oussedik, N.;Collet, C.;Girardot, N.;Poujois, A.",2018,November,http://dx.doi.org/10.1016/j.neurol.2018.08.001,0,0,
3312,Outcomes of WTX101 treatment in a phase 2 and extension study in Wilson disease: Comparison of subjects with and without cirrhosis,"Background: WTX101 (bis-choline tetrathiomolybdate) is a copper-protein-binding agent that reduces plasma nonceruloplasmin bound copper (NCC) in Wilson Disease (WD) by forming tripartite complexes with albumin and increasing biliary copper excretion. In a prospective 24 week single-arm phase 2 study in WD, oral once-daily WTX101 rapidly reduced NCC, improved neurological status, and stabilized liver function. Our aim was to compare baseline characteristics and 48-week extension efficacy and safety in cirrhotic and non-cirrhotic study participants. Methods: Of 28 WD subjects (18-64 years, 15 female) enrolled in the phase 2 study, 13 (46%) were categorized as cirrhotic based on medical history (biopsy or imaging) or estimates of AST-to-platelet ratio. Of 22 subjects who continued WTX101 in the extension, 12 were cirrhotic and 10 non-cirrhotic. Key parameters monitored for 48 weeks included NCC<inf>corrected</inf> (corrected for copper bound in tripartite complexes), hepatic status, disability and neurological status using the Unified Wilson Disease Rating Scale (UWDRS). Results: Mean NCC at study entry was 3.9 muM for non-cirrhotic vs 3.2 muM for cirrhotic subjects. At week 48, mean NCC<inf>corrected</inf> improved to 0.6 and 0.5 muM, respectively. Mean INR was initially higher and albumin lower for cirrhotic vs non-cirrhotic subjects but improved to within the normal range in both groups by week 48. For cirrhotic subjects, mean MELD score improved from 8.4 to 7.5 at week 48, and mean modified Nazer score improved from 1.9 to 0.6. In non-cirrhotic subjects, scores remained stable from study entry to week 48 for MELD (7.0 to 7.1) and modified Nazer (1.0 to 0.8). UWDRS disability and neurological scores improved to week 48 regardless of cirrhosis. Eight serious adverse events possibly or probably related to WTX101 to week 48 were similarly distributed between cirrhotic and noncirrhotic subjects. Reversible ALT elevations requiring dose adjustments were observed in 5 subjects with cirrhosis and 6 without and led to discontinuation in 3 non-cirrhotic subjects before week 24. No ALT elevations requiring dose adjustments were observed in the extension. Conclusion: In summary, after 48 weeks, WTX101 treatment improved copper control with improved or unchanged liver function and a favorable tolerability profile whether or not liver cirrhosis was present. Therefore we conclude that long-term efficacy and safety of treatment with WTX101 was not influenced by the presence or absence of compensated cirrhosis in subjects with WD.",adult;adverse event;aspartate aminotransferase level;biopsy;clinical article;controlled study;disability;drug efficacy;drug safety;drug withdrawal;female;fibrosis;human;human cell;human tissue;international normalized ratio;liver cirrhosis;liver function;medical history;Model For End Stage Liver Disease Score;phase 2 clinical trial;prospective study;rating scale;thrombocyte;Wilson disease;albumin;endogenous compound;conference abstract,"Schilsky, M. L.;Askari, F. K.;Czlonkowska, A.;Ferenci, P.;Ala, A.;Bega, D.;Bronstein, J.;Weiss, K. H.",2018,October,http://dx.doi.org/10.1002/hep.30256,0,0,
3313,Contribution of the French registry in the understanding of Wilson disease,"Objective: To describe patients from the French Wilson disease (WD) registry. Background: WD is a rare genetic disorder caused by loss of function of the ATP7B protein, resulting in toxic copper accumulation in the liver and the brain. Due to its rarity, patients' data are difficult to collect. In France, the WD National reference Centre has a network dedicated to the disease, allowing to collect a maximum of data from these patients. Methods: WD patients resident in France are included in the registry. Data were analyzed at diagnosis and at the last follow-up. Mean age and clinical forms at diagnosis and initial treatments prescribed were reported. At last follow-up, mean duration of the disease, evolution of clinical symptoms and modification of treatments were examined. Results: 619 patients (49.1% males) were included in the registry, their diagnosis being made between 1959 and 2017. Mean age at diagnosis was 18.5 +/-11 years (min 1; max 64). 45.8% had a hepatic phenotype, 33.5% a neurological presentation and 20.7% were diagnosed on familial screening. In the hepatic group, the main initial clinical symptoms were jaundice (49%), ascites (12.7%) and edema (6.9%). Among neurological patients, main initial symptoms were tremor (52,6%), dysarthria (52%), writing difficulties (31%), dystonia (27%), gait disorder (27%), drooling (23%) and dysphagia (14%). Among the living patients (95.2%), mean time between diagnosis and last follow-up was 15 +/-13 years (min 1, max 58). 12.8% of the neurological patients had no more symptoms. Persistent symptoms were dysarthria (45.2%), dystonia (40.9 %), writing difficulties (23.4 %), tremor (21.8%), gait disorder (19.7%) and drooling (13.3%). Between diagnosis and last follow-up, 42% of patients had their treatment modified. D-Penicillamin prescription decreased from 79% to 37% whereas zinc salts and Trientine ones increased from 9% to 32% and 6% to 20% respectively. Bitherapy remained stable (3% vs 2%), 8.5% had a liver transplantation. Side effects that led to a change of treatment were respectively present in 33.7% under D-Penicillamin and 14.3% under zinc salts. Conclusions: This cohort is the largest in Europe and corresponds to two thirds of the WD patients identified in France since 906 prevalent cases were reported in this country in a recent epidemiological study1. These data are fundamental for a better understanding of the disease and to improve patients' care.",adult;ascites;cohort analysis;controlled study;diagnosis;disease course;dysarthria;dysphagia;dystonia;edema;female;follow up;France;gait disorder;human;hypersalivation;jaundice;liver transplantation;major clinical study;male;phenotype;prescription;resident;side effect;tremor;Wilson disease;writing;young adult;penicillamine;trientine;zinc derivative;conference abstract,"Poujois, A.;Girardot, N.;Brunet, A. S.;Lachaux, A.;Woimant, F.",2018,October,,0,0,
3314,Chinese patients with Wilson disease and the treatments: Exampled with Unithiol (DMPS) intravenous infusion,"Objective: The authors performed a retrospective analysis about effects and side-effects for a series of 136 Chinese patients with Wilson disease, treated by Unithiol (DMPS) intravenous infusion, at the University Hospital, Affiliated to Shanghai Jiaotong University School of Medicine. Background: In Europe and America, therapy drugs approved for treating the patients with Wilson disease (WD) mainly include penicillamine and trientine. But in China, trientine is not available for its price is so especially high to the patients. The WD patients with penicillamine allergy or intolerance are recommended to have orally dimercaptosuccinic acid (DMSA) in mainland China safer and cheaper. The main WD specialists in China give Unithiol (DMPS) intravenous infusion for a few of weeks. The authors observed that data about effects of DMPS infusion on blood routine (WBC,N,Hb, Plt) and liver function(ALT,AST,GGT,Alb) is insufficient. We aimed at finding the effects with data from a single center at the University Hospital Shanghai. Methods: All of these 136 patients had blood routine (WBC,N,Hb, Plt) before and after DMPS, and along with liver function(ALT,AST, GGT,Alb) before and after the DMPS infusion. We did analysis with SPSS 20.0. Results: 1.The blood routine(WBC,N,Hb,Plt) had no significant change before and after DMPS treatment(P>0.05); 2.The liver function(ALT,AST,GGT,Alb) had no significant change before and after DMPS treatment(P>0.05); 3. The Urine copper contents increased by 5.5 times. Conclusions: The DMPS infusion therapy has on effect on WD patients' blood routine (WBC,N,Hb,Plt) and liver function(ALT,AST, GGT,Alb). Generally, DMPS is a kind of safe and benificial treatment for these series of WD patients. However rare serious side effects had been reported.",adult;allergy;aspartate aminotransferase level;China;controlled study;data analysis software;drug therapy;Europe;female;human;human tissue;infusion therapy;intravenous drug administration;liver function;major clinical study;male;retrospective study;side effect;university hospital;urine;Wilson disease;endogenous compound;gamma glutamyltransferase;penicillamine;succimer;trientine;unithiol;conference abstract,"Wang, X. P.",2018,October,,0,0,
3315,Targeting GPi: DBS treating dystonia in a patient with Wilson's disease,"Objective: The primary objective is to determine the efficacy of Deep Brain Stimulation (DBS) targeting the internal segment of the globus pallidus (GPi) on treating dystonia associated with Wilson's disease (WD). The secondary objectives are to evaluate the impact of GPi DBS on the cognition aspects of the disease and to evaluate the safety of GPi DBS in the specific context of WD. Background: WD is a rare autosomal recessive inherited disease resulting form mutations affecting the ATP7B copper transporter, leading to copper accumulation in the brain and liver. The common neurological manifestations of WD include dystonia, tremor, ataxia, chorea and parkinsonism. Of these, dystonia is one of the most difficult to manage. While GPi DBS is a therapy option to target dystonic symptoms, there is limited data on the use of this therapy to treat dystonia in WD. In order to evaluate the clinical efficacy of bilateral GPi DBS in the management of WD with dystonia, we present a case of a patient with WD who was implanted with bilateral GPi DBS and evaluated with the Unified Wilson's Disease Rating Scale (UWDRS). The patient's dystonia had not improved on zinc acetate treatment administered two years prior to DBS surgery. Methods: Baseline UWDRS scores were assessed pre-operatively and 1 and 2 months post-operatively.Postsurgical UWDRS scores were compared with the baseline scores and analysis was performed on neurologic, hepatic and psychiatric subscales. In addition, he underwent an extensive neuropsychological evaluation as a part of his DBS approval process and he will be reassessed 6 months after surgery to address our secondary outcome measure of cognition. Results: Compared to the baseline UWDRS scores, his total UWDRS scores improved by 34.48% at his 1 month postoperative evaluation and by 45.98% at his 2 month postoperative evaluation. The neurological subscore improved by 30.99% and 43.66%, respectively. In addition, the patient's hepatic subscale improved by 37.5% and 50%, respectively. At the 1 month postoperative visit, the patient's psychiatric subscale improved by 62.5% and remained stable at the 2 month postoperative follow-up evaluation. Conclusions: While he did demonstrate a significant improvement in his neurological subscales, the improvement in his hepatic and psychiatric subscales likely represent variability in patient self-report more than response to DBS. In particular, his responses on the hepatic subscale likely reflect his improved overall sense of well-being rather than a specific hepatic improvement. Using bilateral GPi DBS to treat WD with prominent dystonia can be effective in ameliorating neurological and psychiatric symptoms. More clinical research should be conducted to further validate the clinical efficacy of bilateral GPi DBS in WD patient with dystonia.",adult;animal experiment;animal model;ataxia;brain depth stimulation;chorea;clinical research;cognition;comparative effectiveness;dystonia;follow up;gene mutation;globus pallidus;liver;male;mental disease;nonhuman;outcome assessment;parkinsonism;rating scale;self report;surgery;tremor;wellbeing;Wilson disease;endogenous compound;Wilson disease protein;zinc acetate;conference abstract,"Sperry, L.;Duan, X.;Girgis, F.;Denny, K.;Farias, S.;Kahn, D.;Medici, V.;Zhang, L.;Shahlaie, K.",2018,October,,0,0,
3316,Tics in Wilson's disease and review of the literature,"Objective: We report a case with tics in a patient with Wilson's Disease (WD). Background: Wilson's disease is a genetic disorder of copper metabolism, leading to liver failure and neurological deficits. The most common neurologic manifestations are midline cerebellar disorders (dysarthria, gait disturbances), movement disorders (parkinsonism, dystonia, tremor) and a bunch of psychiatric disorders. Tics and stereotypic movements are extremely rare in WD. This paper presents a 23-year-old male with WD who displayed stereotypic movements. We reviewed all previous WD cases in the literature that present with tics (five cases) and stereotypic movements. Methods: Case report and literature review. Results: A 23-year-old male was referred to our clinic due to speech disturbance, difficulty in chewing, gait disturbance and involuntary (Figure presented) movements. His mother is his father's first cousin. He has two sisters who were healthy and their blood ceruloplasmin levels were normal. He had stereotypical movements including left-hand elevation and touching to his forehead and flexion of elbow, right hand shaking, elevating left foot and making circular movements which were voluntarily suppressible for a time (video). Also, there were occasional dystonic movements of his right upper limb. Bilateral Kayser-Fleischer rings were seen. Blood tests were remarkable for low ceruloplasmin levels (<0.02 g/L-N:0.22-0.58 g/L). 24-hour urinary copper excretion was 102mug/day and 55,9 mug/day (N:3-35 mug/day) and fourth day after trientine 300 mg twice a day usage, urine copper was 818 mug/day. Cranial MRI showed external capsule hyperintensity on T2/FLAIR (figure 1) , and lentiform, caudate nucleus and bilateral substantia nigra hypointensity on SWI (figure 2). Wilson's Disease was diagnosed and trientine 300 mg three times a day treatment was initiated. [figure 1] [figure 2] Conclusions: Tics are very rare in WD. There are five other cases with stereotypic movements and tics, in the literature summerized in Table. Table 1: Characteristics of the patients in the literature. [table 1]. Stereotypic movements and tics are very rare in WD, and awareness of this situation areimportantsince diagnose and initiating the treatment earlier can make the outcome better.",adult;awareness;case report;caudate nucleus;cerebellum disease;clinical article;copper metabolism;diagnosis;dysarthria;dystonia;elbow;excretion;external capsule;father;female;first cousin;foot;forehead;gait;gene expression;hand;human;human tissue;liver failure;male;mastication;mental disease;nuclear magnetic resonance imaging;parkinsonism;protein blood level;protein expression;sister;substantia nigra;tic;tremor;urine;videorecording;Wilson disease;young adult;ceruloplasmin;endogenous compound;trientine;conference abstract,"Yilmaz, A. Y.;Kuzu Kumcu, M.;Akbostanci, M. C.",2018,October,,0,0,
3317,Explosive flurry of seizures and new-onset cortical-subcortical lesions in a patient with Wilson disease,"Objective: We report a patient with stable neurological Wilson disease (WD) who developed repeated seizures and new-onset corticalsubcortical lesions, and discuss the possible causes for the changes. Background: Cortical-subcortical lesions and seizures have been reported in 5-10% and 4-8% of patients with WD respectively, and are often observed concurrently. However, their occurrence in a stable patient on treatment has not been reported. Methods: An eight year old boy developed progressive dysarthria, gait imbalance and behavioral changes over 18 months. Examination also showed Kayser-Fleischer rings, Wilsonian faces, and generalized dystonia. He could walk independently and maintain high grades at school. WD was diagnosed. T2W and FLAIR brain MRIs showed symmetrical basal ganglial and thalamic lesions; no cortical lesions were present [figure1]. With copper chelation (penicillamine gradually escalated from 125mg/d to 1g/d) there was significant neurological improvement over the next 10 months. At that point though he developed recurrent seizures; initially once every few weeks but, despite antiepileptics, increasing to multiple seizures per day after two months. He became dull, somnolent and unsteady. Repeat brain MRI a year after the first scan showed new-onset patchy lesions in the frontal and parietal cortical-subcortical areas [figure2]. Video EEG showed clinical and electrical frontal lobe seizures. Intravenous benzodiazepine and levetiracetam, and pulse methylprednisolone (to decrease cerebral inflammation), were administered and controlled the seizures promptly. Longer-term antiepileptic treatment was also intensified. Penicillamine was maintained at 1g/d. Cognition and balance recovered over the next few weeks. Results: Very frequent or prolonged seizures (in diseases other than WD) have been shown to lead to acute postictal cortical lesions. Such changes are believed to result from seizure-induced neuronal hyperexcitation, increased cellular metabolic demand and sodium/potassium ATP pump failure. In WD, copper deposits in the cortical grey matterincrease cellular metabolic stress. We hypothesise that repeated seizures heighten this stress markedly, precipitate cellular injury and death, and can lead to new-onset cortical-subcortical lesions and even induce further seizures. Conclusions: Late-onset seizures and concurrent cortical lesions can develop in stable WD patients undergoing treatment. We hypothesize that the seizures may contribute to the development of the lesions. If true, this would suggest that prompt control of seizures can limit such cortical-subcortical lesions.",anticonvulsant therapy;behavior change;brain cortex lesion;case report;cell damage;chelation;child;clinical article;cognition;death;diagnosis;drug combination;dysarthria;electroencephalogram;frontal lobe;gait;generalized dystonia;human;inflammation;male;metabolic stress;nuclear magnetic resonance imaging;precipitation;school child;seizure;videorecording;Wilson disease;adenosine triphosphate;benzodiazepine;levetiracetam;methylprednisolone;penicillamine;sodium;conference abstract,"Aggarwal, A.;Munshi, M.;Gadgil, P.;Sanghvi, D.;Bhatt, M.",2018,October,,0,0,
3318,Neurologic Wilson's disease: Case series on a diagnostic and therapeutic emergency,"Objective: To present two cases of Neurologic Wilson's Disease with two different clinical picture. To review the the important diagnostics and tests in clinching the rare condition. To emphasize the different medications that can be used for patients with Neurologic Wilson's Disease. Background: Wilson's Disease is a rare genetic disease resulting in pathologic deposition of copper in the liver, brain, cornea, kidney and cardiac muscle. Wilson's Disease has a prevalence rate of 30 cases per million qualifying as a rare disease based on the criterion of European Commission on Public Health. Methods: Two cases of Neurologic Wilson's Disease were reviewed. The first one presenting with ataxia and parkisonian symptoms and the other one with dytonic form. Results: Reviewed were two cases of Neurologic Wilson's Disease presenting with progressive movement disorder and Kayser-Fleischer rings with low serum copper, low ceruloplasmin and increased 24-hour urine copper in a background of normal liver enzymes. Cranial Imaging revealed symmetric basal ganglia hyperintensities in T2/FLAIR. 8th International Meeting on Wilson's Disease Scoring System and Unified Wilson Disease Rating Scale were also helpful in the diagnosis and monitoring of patients. For both cases, low copper diet was a mainstay treatment. Zinc supplementation was also initiated with note of remarkable improvements in speech, tremors and stiffening of extremities. The first case underwent D-Penicillamine treatment with slow uptitration of the drug to avoid hematologic consequences and to monitor for paradoxical neurological deterioration, as for the second case, patient was maintained on Zinc supplementation because of relatively severe baseline neurologic status. Treatment should still be individualized since no two patients with Wilson's Disease are the same. For patients with debilitating movement disorder refractory to chelation and medical treatment, botulinum toxin injection maybe offered. Screening of siblings of the patient and monitoring of their serum ceruloplasmin is a big part of management. Conclusions: More often than not, these cases go unnoticed and misdiagnosed because of its rarity and varied presentation. Extensive work-up is necessary to clinch the diagnosis. To date, there is no test, except genetic methods that can be considered diagnostic on its own. As for the management, the earlier the intervention is initiated, the better prognosis would be for recovery. There are several treatment options and should be tailored to every patient with Neurologic Wilson's Disease. Since, Neurologic Wilson's Disease is considered as a Copper Toxicity, immediate diagnostic evaluation and early treatment initiation is a must.",adult;ataxia;basal ganglion;cardiac muscle;case report;case study;ceruloplasmin blood level;chelation;clinical article;copper blood level;cornea;diagnosis;diagnostic error;diet;drug dose titration;emergency;female;human;human tissue;injection;kidney;limb;liver;male;monitoring;prevalence;prognosis;public health;rare disease;rating scale;scoring system;sibling;speech;tremor;urine;Wilson disease;botulinum toxin;ceruloplasmin;endogenous compound;liver enzyme;penicillamine;zinc;conference abstract,"Porlas, R.;De Castillo, L.;Dioquino, C.",2018,October,,0,0,
3319,"Neurological improvement with WTX101 treatment in a Phase 2, multi-center, open label study in Wilson Disease","Objective: The objective of this study was to characterize neurological manifestations in Wilson Disease (WD) patients and describe specific neurological changes after 24 weeks' treatment with WTX101. Background: Substantial unmet needs exist with respect to the efficacy, safety and tolerability of WD treatments. WTX101 (bis-choline tetrathiomolybdate) is an oral investigational first-in-class copper-protein-binding agent, dosed once daily, which rapidly improved disability and neurological status in a prospective 24-week Phase 2 trial in WD. Methods: Adult patients with WD (treatment naive or <=2 years with chelation or zinc therapy) received response-guided individual WTX101 dosing (15-120 mg once daily) for 24 weeks. Changes in neurological status were characterized using the Unified Wilson's Disease Rating Scale (UWDRS). Results: Of the 28 enrolled patients, 25 had neurological manifestations. Baseline mean UWDRS Part II (disability) and III (neurological status) scores were 6.6 (SD 10.0; range 0-35) and 22.8 (SD 21.0; range 0-83), respectively. By week 24, both mean [SD] UWDRS Part II score (4.1 [8.2]; p<0.001) and Part III score (16.6 [17.7]; p<0.0001) improved. There was a highly significant predictive relationship between Parts II and III total scores taken over time (p<0.0001). Most common UWDRS Part III abnormalities at baseline were postural arm tremor (71%), dysarthria (68%), gait (61%) and limb dexterity and coordination scale items e.g. alternating hand movements (71%), finger taps (57%), handwriting (54%) and leg agility (54%). Most severely affected items were handwriting and dysarthria (mean [SD] scores 2.0 [0.8] and 1.8 [0.9], respectively). Largest mean improvements (% change) over 24 weeks were observed for handwriting (51.4%), leg agility (40.8%), postural arm tremor (39.5%) and alternating hand movements (35.0%). Grouping total tremor or limb dexterity and coordination items demonstrated similar improvements (34.2% and 29.2%, respectively). WTX101 was generally well tolerated and early drug-induced neurological worsening was not observed. Conclusions: Neurological manifestations were common in this patient cohort with WD. Improved neurological status after WTX101 treatment correlated with reduced patient-reported disability. Together with its simplified dosing and favorable safety profile, WTX101 has the potential to address unmet needs in WD.",adult;adverse drug reaction;agility;chelation;cohort analysis;congenital malformation;controlled study;coordination;disability;drug efficacy;drug safety;drug therapy;dysarthria;female;finger;gait;hand movement;handwriting;human;leg;limb tremor;major clinical study;male;open study;phase 2 clinical trial;prospective study;rating scale;side effect;Wilson disease;choline tetrathiomolybdate;zinc;conference abstract,"Bega, D.;Bronstein, J.;Nicholl, D.;Askari, F.;Ala, A.;Ferenci, P.;Bjartmar, C.;Weiss, K. H.;Schilsky, M.;Czlonkowska, A.",2018,October,,0,0,
3320,Copper deposition in oligodendroglial cells in an autopsied case of hepatolenticular degeneration,"We present a case of hepatolenticular degeneration, so-called Wilson's disease (WD), in a 31-year-old Japanese man with broader deposition of copper in the liver, kidney and brain. The liver showed severe cirrhotic changes with macronodular pseudolobule formation, but there was little difference in immunohistochemical expression patterns of the copper transporter ATP7B between the control and present case. In the brain, there were both WD-related lesions such as the scattering of Opalski cells and changes caused by hepatic encephalopathy including the appearance of Alzheimer type II glia. Of note, we identified copper deposits in the systemic organs, including hepatocytes, renal tubules, and in broad areas of the brain. Surprisingly, as a result of further pursuit, copper accumulation in the brain was rarely identified in neuronal cells, but in Olig2-positive glial cells with double immunohistochemical staining. Together, this rare autopsied case suggests a novel cellular candidate affected by abnormal copper metabolism and the necessity to perform the systemic examination of copper deposition in WD. Copyright © 2018 Japanese Society of Neuropathology",atp7b;autopsy;copper deposition;oligodendrocyte;Wilson's disease;adult;Alzheimer disease;article;basal ganglion;brain;brain cortex atrophy;case report;clinical article;computer assisted tomography;consciousness;copper blood level;copper metabolism;disease course;dysarthria;esophagus varices;hepatic encephalopathy;human;human tissue;immunohistochemistry;Japanese (people);kidney;kidney tubule;laboratory test;liver;liver biopsy;liver cell;liver cirrhosis;liver dysfunction;liver nodule;male;medical history;nuclear magnetic resonance imaging;oligodendroglia;priority journal;stomach rupture;stomach varices;Wilson disease/di [Diagnosis];copper/ec [Endogenous Compound];trientine;Wilson disease protein/ec [Endogenous Compound],"Nishimuta, M.;Masui, K.;Yamamoto, T.;Ikarashi, Y.;Tokushige, K.;Hashimoto, E.;Nagashima, Y.;Shibata, N.",2018,June,http://dx.doi.org/10.1111/neup.12456,0,0,
3321,Exome sequencing of an adolescent with nonalcoholic fatty liver disease identifies a clinically actionable case of Wilson disease,"Diagnostic whole-exome sequencing has proven highly successful in a range of rare diseases, particularly early-onset genetic conditions. In more common conditions, however, exome sequencing for diagnostic purposes remains the exception. Herewe describe a patient initially diagnosed with a common, complex liver disease, nonalcoholic fatty liver disease (NAFLD), who was determined to have Wilson disease (WD) upon research-related exome sequencing. The patient presented as a 14.5-yr-old adolescent with chronically elevated aminotransferases, normal ceruloplasmin, and histologic examination consistent with NAFLD with advanced fibrosis. He was enrolled in a large longitudinal study of patients with NAFLDand wasfound to haveWDbyexomesequencing performed 4 yr later. This newdiagnosis, confirmed clinically by 24 h urine copper quantification, led to a change in the therapy from lifestyle counseling to directed treatment with D-penicillamine, a copper chelating agent. In this case, the likelihood of making the correct diagnosis and thereby choosing the appropriate treatment was increased by exome sequencing and careful interpretation. This example illustrates the utility of exomesequencing diagnostically in more common conditions not currently considered as targets for genome-wide evaluation and adds to a growing body of evidence that patients diagnosed with more common conditions often in fact have rarer genetically determined syndromes that have escaped clinical detection. Copyright © 2018 Wattacheril et al.",abdominal pain;adolescent;article;case report;clinical article;clinical feature;controlled study;diagnostic accuracy;differential diagnosis;dyslipidemia/dt [Drug Therapy];family history;fatty liver/di [Diagnosis];genomics;headache;hepatomegaly;histopathology;human;human tissue;lifestyle modification;liver biopsy;liver fibrosis/di [Diagnosis];loss of function mutation;missense mutation;molecular diagnosis;nausea;nonalcoholic fatty liver/di [Diagnosis];urinalysis;whole exome sequencing;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];cholesterol/ec [Endogenous Compound];copper/ec [Endogenous Compound];glucose/ec [Endogenous Compound];insulin/ec [Endogenous Compound];omega 3 fatty acid/dt [Drug Therapy];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound],"Wattacheril, J.;Shea, P. R.;Mohammad, S.;Behling, C.;Aggarwal, V.;Wilson, L. A.;Yates, K. P.;Ito, J.;Fishbein, M.;Stong, N.;Lavine, J. E.;Goldstein, D. B.",2018,October,http://dx.doi.org/10.1101/mcs.a003087,0,0,
3322,Pregnancy in Wilson's disease: Management and outcome,"Wilson's disease (WD) is a rare inherited disorder of copper metabolism causing toxic hepatic and neural copper accumulation. Clinical symptoms vary widely, from asymptomatic disease to acute liver failure or chronic liver disease with or without neuropsychiatric symptoms. Continuation of specific medical treatment for WD is recommended during pregnancy, but reports of pregnancy outcomes in WD patients are sparse. In a retrospective, multicenter study, 282 pregnancies in 136 WD patients were reviewed. Age at disease onset, age at conception, and WD-specific treatments were recorded. Maternal complications during pregnancy, rate of spontaneous abortions, and birth defects were analyzed with respect to medical treatment during pregnancy. Worsening of liver function tests was evident during 16 of 282 (6%) pregnancies and occurred in undiagnosed patients as well as in those under medical treatment. Liver test abnormalities resolved in all cases after delivery. Aggravation of neurological symptoms during pregnancy was rare (1%), but tended to persist after delivery. The overall spontaneous abortion rate in the study cohort was 73 of 282 (26%). Patients with an established diagnosis of WD receiving medical treatment experienced significantly fewer spontaneous abortions than patients with undiagnosed WD (odds ratio, 2.853 [95% confidence interval, 1.634-4.982]). Birth defects occurred in 7 of 209 (3%) live births. Conclusion: Pregnancy in WD patients on anticopper therapy is safe. The spontaneous abortion rate in treated patients was lower than that in therapy-naive patients. Although the teratogenic potential of copper chelators is a concern, the rate of birth defects in our cohort was low. Treatment for WD should be maintained during pregnancy, and patients should be monitored closely for hepatic and neurological symptoms. (Hepatology 2018;67:1261-1269). Copyright © 2017 by the American Association for the Study of Liver Diseases.",adult;article;asymptomatic disease;ataxia;cholestasis;congenital malformation;drug withdrawal;dysarthria;female;fetus outcome;HELLP syndrome;human;hyperbilirubinemia;hypertransaminasemia;liver cirrhosis;liver failure;major clinical study;neurologic disease;onset age;pregnancy;pregnancy outcome;pregnant woman;priority journal;retrospective study;spasticity;spontaneous abortion;thrombocytopenia;tremor;Wilson disease/dt [Drug Therapy];young adult;chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Pfeiffenberger, J.;Beinhardt, S.;Gotthardt, D. N.;Haag, N.;Freissmuth, C.;Reuner, U.;Gauss, A.;Stremmel, W.;Schilsky, M. L.;Ferenci, P.;Weiss, K. H.",2018,April,http://dx.doi.org/10.1002/hep.29490,0,0,
3323,High spatial resolution LA-ICP-MS demonstrates massive liver copper depletion in Wilson disease rats upon Methanobactin treatment,"Wilson disease (WD) is a rare genetic disorder of the copper metabolism leading to systemic copper accumulation, predominantly in the liver. The therapeutic approach in WD patients is the generation of a negative copper balance and the maintenance of copper homeostasis, currently by the use of copper chelators such as D-penicillamine (D-PA). However, in circumstances of delayed diagnosis, poor treatment compliance, or treatment failure, mortality is almost certain without hepatic transplantation. Moreover, even after years of D-PA treatment, high liver copper levels are present in WD patients. We have recently suggested the use of the bacterial peptide Methanobactin (MB), which has an outstanding binding affinity for copper, as potentially efficient and patient-friendly remedy against copper damage in WD. Here we substantiate these findings considerably, by demonstrating a significant removal of copper from liver samples of WD rats upon short, one week only, MB treatments. Using laser ablation-inductively coupled plasma-mass spectrometry with a spatial resolution down to 4 mum, we demonstrate that only small copper hotspots remain in MB treated animal livers. We further demonstrate in WD rat liver, seven weeks after the stopped MB treatment, a lower liver copper concentration as compared to untreated control animals. Thus, MB highly efficiently depletes liver copper overload with a sustained therapeutic effect. Copyright © 2018 Elsevier GmbH",Chelation therapy;Copper;Elemental bioimaging;Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS);Methanobactin;Wilson disease;animal experiment;animal model;animal tissue;article;controlled study;drug binding;drug efficacy;drug megadose;laser ablation inductively coupled plasma mass spectrometry;liver level;low drug dose;multiple cycle treatment;nonhuman;priority journal;rat;treatment duration;chelating agent/ip [Intraperitoneal Drug Administration];unclassified drug;copper chelation;liver copper depletion;methanobactin/ip [Intraperitoneal Drug Administration],"Muller, J. C.;Lichtmannegger, J.;Zischka, H.;Sperling, M.;Karst, U.",2018,September,http://dx.doi.org/10.1016/j.jtemb.2018.05.009,0,0,
3324,The steady state pharmacokinetics of trientine in Wilson disease patients,"Purpose: To determine the steady state pharmacokinetics of trientine in children (>= 12 years of age) and adult patients who had been receiving trientine dihydrochloride therapy prior to the study. Methods: Twenty patients were exposed to trientine (trientine dihydrochloride capsules supplied by Univar) after standard oral dosing as part of ongoing therapy. Plasma trientine concentration was determined pre-dose and at 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose. Concentrations of trientine in plasma were determined by LC-MS/MS using a validated bioanalytical method with stable labelled trientine as the internal standard. Results: Trientine was generally absorbed fairly rapidly with a median T<inf>max</inf> of 1.49 h (range, 0.48-4.08 h). There was some variability in exposure, with a 10-fold range in C<inf>max</inf>, and a 13.8-fold range in AUC0-t. This variability was slightly lower when PK parameters were dose-normalised (6.7-fold range in C<inf>max</inf>/D and an 11.6-fold range in AUC0-t/D). The terminal half-life, which could be defined in 14 of the 20 patients, was broadly consistent between patients (range of 2.33 to 6.99 h). There was no marked difference in pharmacokinetics between adult patients (n = 16) and children (n = 4). The C<inf>max</inf> range was 506 to 3100 ng/mL in adults and 309 to 1940 ng/mL in children-the equivalent ranges for AUC0-t were 1240 to 17,100 ng/mL h and 1500 to 8060 ng/mL h. When PK parameters were normalised for administered dose, the C<inf>max</inf>/D and AUC0-t/D for children were contained within the ranges for the adult patients. Conclusions: The steady state pharmacokinetics of trientine in Wilson disease patients were broadly similar to that reported in healthy subjects. Copyright © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.",Pharmacokinetics;Trientine dihydrochloride;Wilson disease;adult;area under the curve;article;child;clinical article;drug blood level;elimination half-life;female;human;liquid chromatography-mass spectrometry;male;maximum concentration;open study;phase 1 clinical trial;priority journal;steady state;time to maximum plasma concentration;Wilson disease/dt [Drug Therapy];trientine/ct [Clinical Trial];trientine/cr [Drug Concentration];trientine/dt [Drug Therapy];trientine/po [Oral Drug Administration];trientine/pk [Pharmacokinetics],"Pfeiffenberger, J.;Kruse, C.;Mutch, P.;Harker, A.;Weiss, K. H.",2018,01 Jun,http://dx.doi.org/10.1007/s00228-018-2424-6,0,0,
3325,A case report of a successful pregnancy in a woman with wilson's disease on zinc sulphate,"Background: Wilson's disease is an autosomal recessive, rare disorder of copper metabolism. Untreated disease usually causes subfertility and in cases where pregnancy does occur often results in miscarriages. However, medications such as Zinc salts and Penicillamine have resulted in successful pregnancy outcomes. We report a case of successful pregnancy in a woman with Wilson's disease on Zinc sulphate. Case: A 19-year-old woman with Wilson's disease, diagnosed a year ago presented to us in her first pregnancy. When diagnosed her Serum Ceruloplasmin was 27 lmol/L and 24 h urinary Cu was 2.28 lmol. AST and ALT were 47 U/L and 54 U/L. Penicillamine was started initially and later converted to Zinc acetate 50 mg tds, 06 months before her presentation. OGTT, liver profile and 2D ECHO at booking (17 + 1) were normal. USS abdomen revealed multiple hypoechoic nodules in liver compatible with changes of Wilson's disease, without portal hypertension. Morphology scan was normal. Zinc sulphate and folic acid were continued. Her liver profile and fetal growth were normal throughout pregnancy. She underwent a caesarean section at 37 weeks due to breech presentation. The baby (girl) was 3650 g and healthy. Discussion: Zinc is increasingly being used in managing Wilson's disease due to its low side effects. It interferes with absorption of copper from gastrointestinal tract; preventing serosal transfer of copper into blood. It is commonly used in pregnancy due to its very low teratogenicity. Patients with Wilson's disease on regular treatment without symptoms are usually able to conceive and have successful pregnancies.",abdomen;adult;aspartate aminotransferase level;breech presentation;case report;ceruloplasmin blood level;cesarean section;clinical article;diagnosis;drug therapy;female;fetus growth;gastrointestinal tract;girl;human;human tissue;infant;liver nodule;morphology;oral glucose tolerance test;portal hypertension;primigravida;serosa;side effect;teratogenicity;two dimensional echocardiography;Wilson disease;young adult;copper;endogenous compound;folic acid;penicillamine;zinc;zinc acetate;zinc sulfate;conference abstract,"Gunathilaka, S.;Lanerolle, S.;Jayalath, J.;Siriwardena, D.;Kodithuwakku, K.;Sumanathissa, R.;Weerakoon, W.",2018,September,http://dx.doi.org/10.1111/ajo.12874,0,0,
3326,Inborn Errors of Metabolism with Movement Disorders: Defects in Metal Transport and Neurotransmitter Metabolism,"Movement disorders in the pediatric age group are largely of the hyperkinetic type. Metal ion accumulation in the central nervous system presents predominantly with movement disorders and over time leads to psychomotor decline. Abnormalities in monoamine and amino acidergic neurotransmitter metabolism present in individuals with a combination of abnormal movements, epilepsy, and cognitive and motor delay. Detailed clinical history, careful examination, appropriate diagnostic work-up with metabolic screening, cerebrospinal fluid neurotransmitters, and targeted genetic testing help with accurate diagnosis and appropriate treatment. This article provides an overview on movement disorders present in childhood secondary to inborn errors of metal transport and neurotransmitter metabolism. Copyright © 2017 Elsevier Inc.",Metal transport;Neurotransmitter metabolism;Pediatric movement disorders;4 aminobutyric acid metabolism;clinical examination;clinical feature;cognitive defect;diagnostic accuracy;disorders of metal metabolism/di [Diagnosis];disorders of metal metabolism/et [Etiology];electromyography;epilepsy;essential tremor/dt [Drug Therapy];genetic analysis;human;hyperekplexia/di [Diagnosis];hyperekplexia/dt [Drug Therapy];hyperekplexia/et [Etiology];hyperglycinemia/di [Diagnosis];hyperglycinemia/dt [Drug Therapy];hyperglycinemia/et [Etiology];inborn error of metabolism/di [Diagnosis];inborn error of metabolism/et [Etiology];laboratory test;medical history;metabolic disorder/di [Diagnosis];metabolic disorder/dt [Drug Therapy];metabolic disorder/et [Etiology];molecular pathology;motor dysfunction/co [Complication];motor dysfunction/et [Etiology];neurodegeneration with brain iron accumulation/di [Diagnosis];neurodegeneration with brain iron accumulation/et [Etiology];nuclear magnetic resonance imaging;psychomotor disorder/co [Complication];review;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];4 aminobutyric acid/ec [Endogenous Compound];6 pyruvoyltetrahydropterin synthase/ec [Endogenous Compound];benzoic acid/cb [Drug Combination];benzoic acid/dt [Drug Therapy];beta adrenergic receptor blocking agent/dt [Drug Therapy];carbamazepine/dt [Drug Therapy];carbidopa plus levodopa/cb [Drug Combination];carbidopa plus levodopa/dt [Drug Therapy];clonazepam/dt [Drug Therapy];dextromethorphan/cb [Drug Combination];dextromethorphan/dt [Drug Therapy];DOPA decarboxylase inhibitor/cb [Drug Combination];DOPA decarboxylase inhibitor/dt [Drug Therapy];guanosine triphosphate cyclohydrolase I/ec [Endogenous Compound];iron/ec [Endogenous Compound];levodopa/cb [Drug Combination];levodopa/dt [Drug Therapy];manganese/ec [Endogenous Compound];metal/ec [Endogenous Compound];neurotransmitter/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];primidone/dt [Drug Therapy];sepiapterin reductase/ec [Endogenous Compound];serotonin/cb [Drug Combination];serotonin/dt [Drug Therapy];succinate semialdehyde dehydrogenase/ec [Endogenous Compound];tetrahydrobiopterin/cb [Drug Combination];tetrahydrobiopterin/dt [Drug Therapy];trientine/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc acetate/dt [Drug Therapy];6 pyruvoyltetrahydropterin synthase deficiency/di [Diagnosis];6 pyruvoyltetrahydropterin synthase deficiency/dt [Drug Therapy];autosomal dominant guanosine triphosphate cyclohydrolase deficiency/di [Diagnosis];autosomal dominant guanosine triphosphate cyclohydrolase deficiency/dt [Drug Therapy];autosomal dominant guanosine triphosphate cyclohydrolase deficiency/et [Etiology];autosomal recessive guanosine triphosphate cyclohydrolase deficiency/di [Diagnosis];autosomal recessive guanosine triphosphate cyclohydrolase deficiency/dt [Drug Therapy];autosomal recessive guanosine triphosphate cyclohydrolase deficiency/et [Etiology];disorders of monoamine metabolism/di [Diagnosis];disorders of monoamine metabolism/et [Etiology];disorders of neurotransmitter metabolism/di [Diagnosis];disorders of neurotransmitter metabolism/et [Etiology];glycine encephalopathy/di [Diagnosis];glycine encephalopathy/dt [Drug Therapy];glycine encephalopathy/et [Etiology];hereditary hyperekplexia/di [Diagnosis];hereditary hyperekplexia/dt [Drug Therapy];hereditary hyperekplexia/et [Etiology];hypermanganesemia with dystonia 1/di [Diagnosis];hypermanganesemia with dystonia 1/et [Etiology];sepiapterin reductase deficiency/dt [Drug Therapy];sepiapterin reductase deficiency/et [Etiology];succinate semialdehyde dehydrogenase deficiency/di [Diagnosis];succinate semialdehyde dehydrogenase deficiency/dt [Drug Therapy];succinate semialdehyde dehydrogenase deficiency/et [Etiology],"Kantamneni, T.;Mondok, L.;Parikh, S.",2018,April,http://dx.doi.org/10.1016/j.pcl.2017.11.010,0,0,
3327,GanDouLing combined with Penicillamine improves cerebrovascular injury via PERK/eIF2alpha/CHOP endoplasmic reticulum stress pathway in the mouse model of Wilson's disease,"We aim to investigate the function and mechanism of GanDouLing combinated with Penicillamine on cerebrovascular injury in Wilson's disease (WD). ELISA was performed to analyze the expression of vascular injury factors. Pathological changes of cerebral vessels were observed by HE stain. Immunohistochemistry assays were performed to analyze the expression of ICAM-1, VCAM-1, and GRP78. Western blotting was measured to analyze the expression of caspase-3, caspase-12, PERK, eIF2alpha, and CHOP. Apoptosis was detected with TUNEL assay. The expression of vascular injury factors and ICAM-1, VCAM-1 was significantly increased by WD and markedly decreased in GanDouLing-Penicillamine group. The expression of caspase-3, caspase-12, PERK, eIF2alpha, and CHOP were obviously expressed in Wilson group, GanDouLing-Penicillamine suppressed apoptosis and endoplasmic reticulum (ER) stress. Our findings suggested that GanDouLing-Penicillamine improved cerebrovascular injury through PERK/eIF2alpha/CHOP ER stress pathway in the mouse model of WD. Copyright © 2018 The Author(s).",animal experiment;animal model;animal tissue;apoptosis;article;brain blood vessel;brain tissue;cerebrovascular accident/dt [Drug Therapy];controlled study;drug mechanism;endoplasmic reticulum stress;enzyme linked immunosorbent assay;female;immunohistochemistry;mouse;nonhuman;protein expression;TUNEL assay;Western blotting;Wilson disease/dt [Drug Therapy];caspase 12/ec [Endogenous Compound];caspase 3/ec [Endogenous Compound];cell protein/ec [Endogenous Compound];Chinese drug/cb [Drug Combination];Chinese drug/dt [Drug Therapy];Chinese drug/ig [Intragastric Drug Administration];Chinese drug/pd [Pharmacology];glucose regulated protein 78/ec [Endogenous Compound];growth arrest and DNA damage inducible protein 153/ec [Endogenous Compound];initiation factor 2alpha/ec [Endogenous Compound];intercellular adhesion molecule 1/ec [Endogenous Compound];penicillamine/cb [Drug Combination];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];unclassified drug;vascular cell adhesion molecule 1/ec [Endogenous Compound];gandouling/cb [Drug Combination];gandouling/do [Drug Dose];gandouling/dt [Drug Therapy];gandouling/ig [Intragastric Drug Administration];gandouling/pd [Pharmacology];protein PERK/ec [Endogenous Compound],"Chen, Y.;Zhang, B.;Cao, S.;Huang, W.;Liu, N.;Yang, W.",2018,19 Sep,http://dx.doi.org/10.1042/BSR20180800,0,0,
3328,"Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India","Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties. Copyright © 2018 Indian National Association for Study of the Liver",genetic disorder;modified Leipzig scoring;rare disease;Wilson's disease scoring;article;ceruloplasmin blood level;child;controlled study;copper blood level;family history;gastroenterology;human;human tissue;India;liver disease;liver graft;Medline;monitoring;motor dysfunction;neurology;nutrition;organization;practice guideline;prospective study;provocation test;retrospective study;scoring system;urine;Wilson disease;bilirubin;ceruloplasmin;endogenous compound;penicillamine,"Nagral, A.;Sarma, M. S.;Matthai, J.;Kukkle, P. L.;Devarbhavi, H.;Sinha, S.;Alam, S.;Bavdekar, A.;Dhiman, R. K.;Eapen, C.;Goyal, V.;Mohan, N.;Kandadai, R. M.;Sathiyasekaran, M.;Poddar, U.;Sibal, A.;Sankaranarayanan, S.;Srivastava, A.;Thapa, B. R.;Wadia, P.;Yachha, S. K.;Dhawan, A.",2018,,http://dx.doi.org/10.1016/j.jceh.2018.08.009,0,0,
3329,Neurological gait disorders in childhood,"There are an enormous number of neurological illnesses that can manifest with gait disturbance in childhood. Whilst experience and clinical acumen are helpful in diagnosing these disorders, some basic principles in assessment and diagnosis are helpful in determining the phenomenology, time course, and neuro-anatomical localisation. In this review we focus on some of the more common movement disorders resulting in inserted postures (including spasticity and dystonia), inserted movements (including chorea and myoclonus), and impairment of motor control (including ataxia and neuro-muscular disorders). A number of case studies are included to illustrate the factual descriptions. Copyright © 2018 Elsevier Ltd",ataxia;chorea;dystonia;gait disorders in childhood;myoclonus;spasticity;adolescent;anxiety disorder;ataxia/di [Diagnosis];ataxia/et [Etiology];ataxia/th [Therapy];athetosis/di [Diagnosis];athetosis/et [Etiology];athetosis/th [Therapy];brain depth stimulation;case report;cerebellum atrophy/di [Diagnosis];cerebral palsy;cerebrospinal fluid;child;chorea/di [Diagnosis];chorea/et [Etiology];chorea/th [Therapy];clinical article;depression;differential diagnosis;dystonia/di [Diagnosis];dystonia/dt [Drug Therapy];dystonia/et [Etiology];dystonia/th [Therapy];female;follow up;gait disorder/di [Diagnosis];gene mutation;genetic association;genetic screening;human;low drug dose;male;motor dysfunction;myoclonus/di [Diagnosis];myoclonus/et [Etiology];myoclonus/th [Therapy];neurologic examination;neurologic gait disorder/di [Diagnosis];neurologic gait disorder/et [Etiology];neurologic gait disorder/th [Therapy];neuromuscular disease/di [Diagnosis];nuclear magnetic resonance imaging;physiotherapy;polymerase chain reaction;preschool child;review;seizure;spasticity/di [Diagnosis];spasticity/et [Etiology];spasticity/th [Therapy];treatment duration;treatment indication;walking difficulty;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];x-ray computed tomography;acetazolamide;benzodiazepine derivative/dt [Drug Therapy];botulinum toxin/dt [Drug Therapy];carbamazepine/do [Drug Dose];carbamazepine/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent;copper/ec [Endogenous Compound];levetiracetam;sulpiride;tetrabenazine;unclassified drug;valproic acid;zinc;ADCY 5 gene;ankle varus;APTX gene;ATP1A3 gene;Atp7b gene;DYT11 gene;functional gait disorder/di [Diagnosis];GNAO1 gene;hereditary spastic paraparesis type 10;KCNA1 gene;KIF5A gene;motor control impairment;neuromuscular weakness/di [Diagnosis];nkx2 1 gene;PRRT2 gene;Tor1a gene;trientene,"Smith, M.;Kurian, M. A.",2018,October,http://dx.doi.org/10.1016/j.paed.2018.07.006,0,0,
3330,Brain copper storage after genetic long-term correction in a mouse model of Wilson disease,"Wilson disease is a rare autosomal recessive condition caused by mutations in the copper-transporting ATPase ATP7B gene (OMIM: 606882) provoking loss of function and resulting in variable hepatic and neurologic symptoms. Currently, the treatment of Wilson disease focuses on achieving a negative copper balance either with chelators (e.g., d-penicillamine, trientine, and tetrathiomolybdate) or zinc, which reduces copper absorption, or a combination thereof. 1 However, these lifelong treatment regimens often cause side effects and do not restore normal copper metabolism. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",animal experiment;animal model;animal tissue;article;brain level;brain tissue;codon;controlled study;gene expression;male;mass spectrometry;metal metabolism;mouse;nonhuman;priority journal;promoter region;viral gene delivery system;viral gene therapy;Wilson disease/dt [Drug Therapy];adeno associated virus vector;copper;Wilson disease protein/dt [Drug Therapy];copper storage,"Uerlings, R.;Moreno, D.;Murillo, O.;Gazquez, C.;Hernandez-Alcoceba, R.;Gonzalez-Aseguinolaza, G.;Weiskirchen, R.",2018,01 Jun,http://dx.doi.org/10.1212/NXG.0000000000000243,0,0,
3331,Pregnancy in Wilson disease,,adult;amenorrhea;blood clotting disorder;chelation therapy;cholestasis;cohort analysis;congenital malformation;disease association;disease exacerbation;editorial;female;female infertility;human;hypothalamus hypophysis system;liver cirrhosis;liver function;major clinical study;obstetric delivery;oligomenorrhea;ovary function;portal hypertension;pregnancy;priority journal;retrospective study;spontaneous abortion;Wilson disease/dt [Drug Therapy];liver enzyme/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Rabiee, A.;Hamilton, J. P. A.",2018,April,http://dx.doi.org/10.1002/hep.29619,0,0,
3332,Modality of treatment and potential outcome of Wilson disease in Taiwan: A population-based longitudinal study,"Background/Purpose: This study aimed to investigate the epidemiology, the preference of medication, and the potential outcome of Wilson disease in Taiwan. We aimed to provide better therapeutic options for patients with Wilson disease based on the data generated from this study. Methods: We utilized the National Health Insurance Research Database (NHIRD), which stores clinical records of nearly 99% of Taiwan's residents. The database used is a random sample of two-million out of 23-million beneficiaries in Taiwan's NHIRD in 2005. The integrated medical records of these two-million cases were collected from 2000 to 2011. Subjects of Wilson disease were identified as those with International Classification of Diseases, Ninth Revision (ICD-9) code 275.1 and the specific prescription drugs (including D-penicillamine, zinc, and trientine) in either outpatient clinic or inpatient records. Results: During the study period, 66 cases of Wilson disease were identified. The male to female ratio was 1.75. The average prevalence rate was 1.81 per 100,000 and the average annual diagnosis rate was 0.22 per 100,000. The diagnosis was mostly established at 20-24 and 10-14 years of age, followed by 25-29 years. Fifty four of all subjects (81.8%) started the treatment with D-penicillamine, compared with zinc (12.1%) and trientine (6.1%). Among these 66 cases, 27 (40.9%) had liver cirrhosis and three (4.5%) underwent liver transplantation due to liver failure. Conclusion: D-penicillamine is still the most popular prescription of Wilson disease, followed by zinc monotherapy. Although chronic liver injury cannot be avoided, a favorable potential outcome is well demonstrated in this population-based study. Copyright © 2017",Outcome;Taiwan;Therapy;Wilson disease;adolescent;adult;age;article;child;clinical outcome;drug preference;end stage liver disease;female;fulminant hepatic failure;hospital patient;human;icd-9;liver cirrhosis/su [Surgery];liver transplantation;longitudinal study;major clinical study;male;medical record;national health insurance;outpatient department;population research;prevalence;sex ratio;Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];penicillamine/cm [Drug Comparison];penicillamine/dt [Drug Therapy];trientine/cm [Drug Comparison];trientine/dt [Drug Therapy];zinc derivative/cm [Drug Comparison];zinc derivative/dt [Drug Therapy],"Tai, C. S.;Wu, J. F.;Chen, H. L.;Hsu, H. Y.;Chang, M. H.;Ni, Y. H.",2018,May,http://dx.doi.org/10.1016/j.jfma.2017.05.008,1,1,3
3333,Wilson's disease combined with systemic lupus erythematosus: A case report and literature review,"Background: Wilson's disease (WD) is an inherited disorder in which defective biliary excretion of copper leads to its accumulation, particularly in the liver and brain. Systemic lupus erythematosus (SLE) is a multi-system disorder that can manifest in any system. Cases with concomitant WD and SLE, unrelated to treatment with penicillamine, have been rarely reported. Case presentation: We report a case of a young woman who had typical neuropsychiatric symptoms and laboratory tests results of WD. She also had concomitant massive hematuria and proteinuria, fever, multiple positive autoimmune antibodies, hypocomplementemia, abnormal lumbar puncture findings and evidence of Sjogren syndrome, which are all rare in WD. Hence, we considered the diagnosis of SLE. Tapering of steroid dosage also confirmed the diagnosis. Conclusion: Wilson's disease and SLE have varied clinical manifestations. Herein, we reported a rare case in which the two conditions concomitantly existed. In clinical practice, differential diagnosis of the two diseases is necessary for patients with hepatic, neurological, and psychiatric manifestations. Copyright © 2018 The Author(s).",Systemic lupus erythematosus;Wilson's disease;adult;article;basal ganglion;case report;clinical article;clinical feature;clinical practice;differential diagnosis;disease association;drug dose reduction;electroencephalography;female;fever;hematuria;human;hypocomplementemia;intracranial pressure;involuntary movement;keratoconjunctivitis sicca;laboratory test;limb movement;lumbar puncture;magnetic resonance angiography;mental disease;mouth ulcer;nuclear magnetic resonance imaging;physical examination;proteinuria;Sjoegren syndrome;slit lamp microscopy;slurred speech;symptomatology;systemic lupus erythematosus/di [Diagnosis];systemic lupus erythematosus/dt [Drug Therapy];thalamus;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];x-ray computed tomography;xerostomia;young adult;autoantibody/ec [Endogenous Compound];hydroxychloroquine/dt [Drug Therapy];methylprednisolone/dt [Drug Therapy];penicillamine/dt [Drug Therapy];steroid,"Zhang, Y.;Wang, D.;Wei, W.;Zeng, X.",2018,15 Jun,http://dx.doi.org/10.1186/s12883-018-1085-5,0,0,
3334,Modulating chemosensitivity of tumors to platinum-based antitumor drugs by transcriptional regulation of copper homeostasis,"Platinum (Pt)-based antitumor agents have been effective in treating many human malignancies. Drug importing, intracellular shuffling, and exporting-carried out by the high-affinity copper (Cu) transporter (hCtr1), Cu chaperone (Ato x1), and Cu exporters (ATP7A and ATP7B), respectively-cumulatively contribute to the chemosensitivity of Pt drugs including cisplatin and carboplatin, but not oxaliplatin. This entire system can also handle Pt drugs via interactions between Pt and the thiol-containing amino acid residues in these proteins; the interactions are strongly influenced by cellular redox regulators such as glutathione. hCtr1 expression is induced by acute Cu deprivation, and the induction is regulated by the transcription factor specific protein 1 (Sp1) which by itself is also regulated by Cu concentration variations. Copper displaces zinc (Zn) coordination at the zinc finger (ZF) domains of Sp1 and inactivates its DNA binding, whereas Cu deprivation enhances Sp1-DNA interactions and increases Sp1 expression, which in turn upregulates hCtr1. Because of the shared transport system, chemosensitivity of Pt drugs can be modulated by targeting Cu transporters. A Cu-lowering agent (trientine) in combination with a Pt drug (carboplatin) has been used in clinical studies for overcoming Pt-resistance. Future research should aim at further developing effective Pt drug retention strategies for improving the treatment efficacy. Copyright © 2018 by the authors. Licensee MDPI, Basel, Switzerland.",Cisplatin;Drug-resistance;HCtr1;High-affinity copper transporter;Ovarian cancers;Sp1;bioavailability;cancer chemotherapy;chemosensitivity;DNA binding;drug retention;gene;gene expression;gene expression regulation;homeostasis;Menkes syndrome;nonhuman;ovary cancer;oxidation reduction reaction;review;transcription regulation;upregulation;Wilson disease;zinc finger motif;antineoplastic agent;carboplatin;chaperone;copper;glutathione/ec [Endogenous Compound];membrane protein/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];oxaliplatin;transcription factor/ec [Endogenous Compound];transcription factor Sp1/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound];hCTR1 gene;copper exporter,"Lai, Y. H.;Kuo, C.;Kuo, M. T.;Chen, H. H. W.",2018,16 May,http://dx.doi.org/10.3390/ijms19051486,0,0,
3335,Are there genetic variants to explain the phenomenon of donor cell survival following blood transfusion?,"Background/Case Studies: Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (transfusion-associated microchimerism (TAM)) remains a long-term consequence of red blood cell (RBC) transfusion in some patient groups. The mechanism by which donor leukocytes survive following blood transfusion is unclear and it has been speculated that genetic factors may be one pos-sible reason. This study was conducted to determine whether there is any association between an individual's genetic profile and the establishment of TAM in blood transfusion recipients. Study Design/Method: Australian trauma patients (n = 86) transfused with RBC units between 2000 and 2012, with an injury severity score of greater than 15, were recruited. Twelve of these patients were found to have TAM. To date, whole exome sequencing was conducted on four patients with TAM and four patients without TAM. Alignment of the exome data to the human genome reference sequence assembly GRCh37 was conducted and analysis of differential genetic variations was carried out. Variations unique to at least 50% of patients in each group were further investigated, with a primary focus on genes associated with immune regulation. Results/Finding: Preliminary analysis has been performed. Many of the changes found in 2 of the four patients with TAM, were present in highly heterogenous genes including zinc finger protein genes and the human leukocyte antigen genes (HLA-B and HLD-DRB1). Some of the most interesting changes were found in genes with unknown function such as Chr4 70257329 variant ID248066. In addition changes were found in the following genes, BTN3A1 gene (Chr6 26405815 variant ID 340887) which has a role in the regulation and proliferation of T-cells and in the CCL8 gene (chr 17 32647356 variant ID 847320) which is a chemokine that contributes to tumor associated leukocyte removal. Conclusion: Next generation (whole exome) sequencing technologies allow for the exploration of genetic variations across different population groups, which can provide clues for the potential indications of mechanisms by which TAM may establish in certain patients. This preliminary analysis provides potential genetic changes that could involve genes that have a role in T-cell regulation and proliferation. It is expected that further analysis with expanded patient numbers will allow for this genomic data to be explored in more detail. Australian governments fund the Australian Red Cross Blood Service to provide blood, blood products and services to the Australian community.",adult;blood bank;blood transfusion;cell proliferation;cell survival;erythrocyte;female;genetic variability;genetic variation;government;human;human cell;human genome;immunoregulation;injury scale;major clinical study;male;population group;recipient;red cross;T lymphocyte;tumor associated leukocyte;whole exome sequencing;endogenous compound;HLA B antigen;HLA DRB3 antigen;leukocyte antigen;monocyte chemotactic protein 2;zinc finger protein;conference abstract,"Hirani, R.;Hobbs, M.;Statham, A.;Dinger, M.;Irving, D. O.",2018,October,http://dx.doi.org/10.1111/trf.14903,0,0,
3336,Wilson's disease presenting during pregnancy: A diagnostic and therapeutic dilemma,"Wilson's disease is an autosomal recessive genetic disorder affecting copper transport leading to hepatic and/or neuropsychiatric manifestations. Changes in pregnancy can mimic certain clinical features of chronic liver disease such as spider naevi, and constraints for the use of various investigation for diagnosis pose a challenge to physicians. A high index of suspicion, multi-disciplinary team approach, use of correct non-invasive testing including viral serology, autoantibodies and copper studies and ultrasonography help to diagnose most of the pre-existing, de novo or pregnancy-specific hepatological conditions. We report a case of Wilson's disease diagnosed during pregnancy and discuss the challenges in diagnosis and treatment in pregnancy. Copyright © The Author(s) 2017.",Gastroenterology;hepatology;high-risk pregnancy;adult;Apgar score;article;artificial ventilation;ascites;ataxia/si [Side Effect];cardiogenic shock;case report;cholestasis;clinical article;echocardiography;echography;episiotomy;esophagus varices/di [Diagnosis];esophagus varices/dt [Drug Therapy];female;fetus growth;fetus lung maturity;fetus monitoring;gastrointestinal endoscopy;hematemesis/dt [Drug Therapy];human;hypoalbuminemia/di [Diagnosis];infant;international normalized ratio;intrauterine growth retardation;liver cirrhosis;Mallory Weiss syndrome;microcephaly;neonatal respiratory distress syndrome;nuclear magnetic resonance imaging;pallor;patent ductus arteriosus/di [Diagnosis];platelet count;portal hypertension/dt [Drug Therapy];postoperative complication;pregnancy;premature fetus membrane rupture/dt [Drug Therapy];priority journal;respiratory distress;slit lamp microscopy;splenomegaly;tremor/si [Side Effect];urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];wound dehiscence/co [Complication];alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];antibiotic agent/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];corticosteroid;hemoglobin/ec [Endogenous Compound];lead chromate;omeprazole/dt [Drug Therapy];propranolol/dt [Drug Therapy];zinc acetate/ae [Adverse Drug Reaction];zinc acetate/dt [Drug Therapy],"Durairaj, J.;Shanbhag, E. R.;Veena, P.;Gowda, M.;Keepanasseril, A.",2018,01 Sep,http://dx.doi.org/10.1177/1753495X17743162,0,0,
3337,"Insights into trace metal metabolism in health and disease from PET: ""pET metallomics""","Essential trace metals such as copper, zinc, iron, and manganese perform critical functions in cellular and physiologic processes including catalytic, regulatory, and signaling roles. Disturbed metal homeostasis is associated with the pathogenesis of diseases such as dementia, cancer, and inherited metabolic abnormalities. Intracellular pathways involving essential metals have been extensively studied but whole-body fluxes and transport between different compartments remain poorly understood. The growing availability of PET scanners and positron-emitting isotopes of key essential metals, particularly <sup>64</sup>Cu, <sup>63</sup>Zn, and <sup>52</sup>Mn, provide new tools with which to study these processes in vivo. This review highlights opportunities that now present themselves, exemplified by studies of copper metabolism that are in the vanguard of a new research front in molecular imaging: ""PET metallomics."" Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging.",<sup>64</sup>Cu;Copper trafficking;Metallomics;Positron emission tomography;article;blood brain barrier;carcinogenesis;copper metabolism;dosimetry;drug accumulation;drug excretion;drug half life;genetic screening;glioblastoma;homeostasis;human;in vitro study;in vivo study;inductively coupled plasma mass spectrometry;iron metabolism;liver biopsy;loss of function mutation;melanoma;metal metabolism;nerve degeneration;nonhuman;priority journal;prostate cancer;Wilson disease;zinc metabolism;ceruloplasmin/ec [Endogenous Compound];copper 62/pk [Pharmacokinetics];copper 64/pk [Pharmacokinetics];iron 52/pk [Pharmacokinetics];radiopharmaceutical agent/pk [Pharmacokinetics];unclassified drug;Wilson disease protein/ec [Endogenous Compound];zinc 65/pk [Pharmacokinetics];ATP7B gene;manganese metabolism;manganese 51/pk [Pharmacokinetics];manganese 52/pk [Pharmacokinetics];zinc 62/pk [Pharmacokinetics];zinc 63/pk [Pharmacokinetics],"Bartnicka, J. J.;Blower, P. J.",2018,01 Sep,http://dx.doi.org/10.2967/jnumed.118.212803,0,0,
3338,Wilson's disease in 2018,"Wilson's disease (WD) is characterized by deleterious copper accumulation in the liver and the brain. It is one of those rare genetic disorders that benefits from effective treatments which have dramatically transformed the prognosis. The establishment of a national reference center in 2005 that was re-certified this year and the inclusion of patients in a national registry allowed us to progress in the knowledge and management of this rare disease. In France, the clinical prevalence is estimated to 1.5/100 000 but the genetic prevalence is higher around 1/7,000. An incomplete penetrance of the gene or the presence of modifier genes may account for the difference. The clinical spectrum of WD is wider as expected with pauci-symptomatic presentations and a late onset of the disease over the age of 40 in 6 % of patients. WD is suspected when ceruloplasminemia is low and 24h-urinary copper excretion is elevated. Recently, a major diagnostic advance has been reached with the implementation of the direct dosage of toxic free copper, called exchangeable copper. The ratio of exchangeable copper/total copper (REC) > 18.5 % provides the diagnostic of WD with high sensitivity and specificity. Moreover, copper exchangeable > 2.08 mumol/L at diagnosis is indicative of the severity of the extra-hepatic (brain and retina) involvement. Treatment of WD is based on an initial active and prolonged chelating phase (by Trolovol<sup></sup> or Trientine<sup></sup>) followed by a maintenance phase with Trientine<sup></sup> or Zinc salt. The two major problems which may be encountered are neurological worsening during the initial phase and non-compliance to treatment during the maintenance phase. Liver transplantation is the recommended therapeutic option in WD with acute liver failure or end-stage liver cirrhosis; its indication should be considered when a rapid neurological worsening occurs despite effective chelation. Regular clinical, biological and liver ultrasound follow-up is essential to evaluate treatment efficacy, tolerance and adherence but also to detect the appearance of hepatocellular carcinoma on a cirrhotic liver. The near future is promising with the arrival of a new chelator, tetrathiomolybdate and with the development of gene therapy. Copyright © 2018 Elsevier Masson SAS",atp7b;Chelators;Copper;Liver transplant;Wilson's disease;acute liver failure/su [Surgery];follow up;France;gene therapy;human;liver cirrhosis/su [Surgery];liver transplantation;penetrance;prognosis;rare disease/di [Diagnosis];rare disease/et [Etiology];short survey;urinary excretion;Wilson disease/di [Diagnosis];Wilson disease/et [Etiology];Wilson disease/su [Surgery];penicillamine;tetrathiomolybdic acid;trientine;zinc derivative,"Poujois, A.;Chaine, P.;Woimant, F.",2018,September,http://dx.doi.org/10.1016/j.praneu.2018.01.002,0,0,
3339,Six-year clinical and MRI quantitative susceptibility mapping (QSM) follow-up in neurological Wilson's disease under zinc therapy: a case report,,article;case report;clinical article;drug therapy;follow up;human;nuclear magnetic resonance imaging;Wilson disease;zinc,"Zaino, D.;Chiarotti, I.;Battisti, C.;Salvatore, S.;Federico, A.;Cerase, A.",2018,,http://dx.doi.org/10.1007/s10072-018-3557-1,0,0,
3340,Associations between zinc deficiency and metabolic abnormalities in patients with chronic liver disease,"Zinc (Zn) is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients. Copyright © 2018 by the authors. Licensee MDPI, Basel, Switzerland.",HCV-related chronic liver disease;Hepatic encephalopathy;Hepatic steatosis;Insulin resistance;Insulin-like growth factor-1;Iron overload;Lipid peroxidation;Liver cirrhosis;Nonalcoholic steatohepatitis;Zinc deficiency;apoptosis;chronic hepatitis;chronic liver disease;congenital malformation;hemochromatosis;hepatitis C;homeostasis;human;hypoalbuminemia;intestine absorption;liver cell carcinoma;metabolic disorder;nonalcoholic fatty liver;oxidative stress;review;signal transduction;Wilson disease;zinc metabolism;copper;iron;retinoic acid;selenium;somatomedin C/ec [Endogenous Compound];tyrosine;zinc;zinc acetate;zinc sulfate,"Himoto, T.;Masaki, T.",2018,14 Jan,http://dx.doi.org/10.3390/nu10010088,0,0,
3341,A case report of misdiagnosis of psychotic symptoms predominant Wilson's disease,"Wilson's disease is an autosomal recessive disease of abnormal copper metabolism. Psychosis is a rare manifestation of Wilson's disease. Few cases of misdiagnosing Wilson's disease as an etiology of psychosis were reported in the literature. We report a case of a 42-year-old patient, who was diagnosed with a schizoaffective disorder and treated with antipsychotics for 3 years with no significant improvement. On reevaluation, we the patient was diagnosed to have Wilson's disease. The patient's symptoms improved significantly with chelation therapy. Copyright © 2018 Journal of Neurosciences in Rural Practice Published by Wolters Kluwer - Medknow.",Misdiagnosis;psychosis;Wilson's disease;adult;article;case report;ceruloplasmin blood level;chelation therapy;clinical article;clinical feature;diagnostic error;disease severity;drug effect;drug efficacy;drug response;dysarthria;human;lack of drug effect;muscle hypertonia;priority journal;schizoaffective psychosis/di [Diagnosis];schizoaffective psychosis/dt [Drug Therapy];tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];olanzapine/dt [Drug Therapy];risperidone/dt [Drug Therapy];valproic acid/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Shah, B.;Limbu, S.",2018,October-December,http://dx.doi.org/10.4103/jnrp.jnrp_515_17,0,0,
3342,Wilson disease,"Wilson disease (WD) is a potentially treatable, inherited disorder of copper metabolism that is characterized by the pathological accumulation of copper. WD is caused by mutations in ATP7B, which encodes a transmembrane copper-transporting ATPase, leading to impaired copper homeostasis and copper overload in the liver, brain and other organs. The clinical course of WD can vary in the type and severity of symptoms, but progressive liver disease is a common feature. Patients can also present with neurological disorders and psychiatric symptoms. WD is diagnosed using diagnostic algorithms that incorporate clinical symptoms and signs, measures of copper metabolism and DNA analysis of ATP7B. Available treatments include chelation therapy and zinc salts, which reverse copper overload by different mechanisms. Additionally, liver transplantation is indicated in selected cases. New agents, such as tetrathiomolybdate salts, are currently being investigated in clinical trials, and genetic therapies are being tested in animal models. With early diagnosis and treatment, the prognosis is good; however, an important issue is diagnosing patients before the onset of serious symptoms. Advances in screening for WD may therefore bring earlier diagnosis and improvements for patients with WD. Copyright © 2018, Springer Nature Limited.",chelation therapy;clinical feature;copper metabolism;disease course;disease exacerbation;disease severity;DNA determination;early diagnosis;epigenetics;gene mutation;gene therapy;homeostasis;human;liver disease;liver transplantation;mental disease;neurologic disease;nonhuman;pathophysiology;priority journal;prognosis;quality of life;review;treatment planning;Wilson disease/di [Diagnosis];Wilson disease/dm [Disease Management];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/pc [Prevention];Wilson disease/su [Surgery];copper exporting adenosine triphosphatase;inorganic salt;penicillamine/dt [Drug Therapy];tetrathiomolybdic acid;trientine/dt [Drug Therapy];zinc derivative,"Czlonkowska, A.;Litwin, T.;Dusek, P.;Ferenci, P.;Lutsenko, S.;Medici, V.;Rybakowski, J. K.;Weiss, K. H.;Schilsky, M. L.",2018,01 Dec,http://dx.doi.org/10.1038/s41572-018-0018-3,0,0,
3343,Successful Treatment of Hypersplenism in Wilson's Disease by Partial Splenic Embolization,"Aim: Hypersplenism can occur in patients with Wilson's disease (WD). Surgical splenectomy is a conventional treatment for this condition; however, emotional and neurological deterioration may follow splenectomy. In recent years, partial splenic embolization (PSE) has been increasingly performed as a nonsurgical alternative treatment for hypersplenism. The aim of this study was to evaluate the effectiveness and safety of PSE compared with splenectomy in the treatment of hypersplenism in WD patients. Methods: Fifty WD patients with hypersplenism were randomly divided into two groups (group A and group B), each including 25 patients. Patients in groups A and B were treated with PSE and splenectomy, respectively. Data were collected on the clinical efficacy of each procedure, adverse reactions, hematologic and blood chemistry test results, and abdominal computed tomography (CT) scan findings (group A only). Results: Marked improvements in the platelet and leukocyte counts after PSE and splenectomy were observed in all patients. PSE was associated with improved liver function without severe complications, and no significant changes in emotional and neurological symptoms were observed. In contrast, seven WD patients suffered neurological deterioration after splenectomy. Conclusions: Hypersplenism in WD patients was successfully treated by PSE, which appears to be a safe and effective alternative treatment for WD-induced hypersplenism. Copyright © 2017 The Author(s). Published by Taylor & Francis Group, LLC © 2017, © Liang-Yong Li, Huai-Zhen Chen, Yuan-Cheng Bao, Qing-Sheng Yu, and Wen-Ming Yang.","hypersplenism;neurological deterioration;partial splenic embolization;sodium 2,3-dimercapto-1-propane sulfonate (DMPS);splenectomy;Wilson's disease;abdominal pain;adolescent;adult;article;artificial embolization;ascites;blood chemistry;ceruloplasmin blood level;clinical article;computer assisted tomography;controlled study;deterioration;disease severity;emotional disorder;female;fever;human;hypersplenism/th [Therapy];intermethod comparison;leukocyte count;liver function;liver level;male;nausea and vomiting;neurologic disease;platelet count;pleura effusion;postoperative complication;postoperative pain;priority journal;syndrome;Wilson disease;x-ray computed tomography;alanine aminotransferase/ec [Endogenous Compound];albumin/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];globulin/ec [Endogenous Compound];penicillamine;postembolization syndrome","Li, L. Y.;Chen, H. Z.;Bao, Y. C.;Yu, Q. S.;Yang, W. M.",2018,04 Mar,http://dx.doi.org/10.1080/08941939.2016.1278058,0,0,
3344,Maternal and perinatal outcome of wilson disease in pregnancy: A 5-year experience at a tertiary care center,"Introduction: Wilson disease is a very rare inherited autoso-mal recessive disorder, with an incidence of 1 in 30,000 live births, associated with impaired copper metabolism leading to decreased biliary excretion and accumulation of copper in the liver and brain. Patients may be asymptomatic or might present with fulminant liver disease or neuropsychiatric illness. Untreated Wilson disease is related to infertility/subfertility/recurrent pregnancy loss. Aim: To study the maternal and perinatal outcomes of Wilson disease in pregnancy. Materials and methods: It is a retrospective observational study carried out in the Department of Obstetrics and Gynecology, St. John's Medical College Hospital, Bengaluru, India, between November 2010 and November 2015. Five patients with Wilson disease were identified during the study period. Pregnancy outcome was good in all these five women who were on regular treatment. Conclusion: Patients with Wilson disease who receive regular treatment and who remain asymptomatic and conceive normally have favorable pregnancy outcomes. They merit regular surveillance and active management in higher centers with multidis-ciplinary approach involving gastroenterologists, obstetricians, neurologists, and intensivists. Copyright © 2017, Jaypee Brothers Medical Publishers (P) Ltd. All rights reserved.",D-penicillamine;Perinatal outcome;Pregnancy;Wilson disease;adult;Apgar score;article;case report;cholecystectomy;cholelithiasis/pv [Special Situation for Pharmacovigilance];clinical article;copper metabolism;disease association;epistaxis;erythrocyte transfusion;female;female infertility;human;observational study;pancytopenia;pregnancy outcome;premature fetus membrane rupture;psychosis/dt [Drug Therapy];retrospective study;tertiary care center;thrombocytopenia;Wilson disease/dt [Drug Therapy];young adult;haloperidol/dt [Drug Therapy];penicillamine/dt [Drug Therapy];quetiapine/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc/dt [Drug Therapy],"Vishnupriya, K. M. N.;Sheela, C. N. R.;Thayumanasundaram, M.",2017,October-December,http://dx.doi.org/10.5005/jp-journals-10006-1521,0,0,
3345,"Clinical features, laboratory findings and prognosis in fulminant Wilson's disease","Introduction:We evaluated 16 years of experience of pediatric patients with fulminant Wilson's disease (WD). Materials and Methods: Of 98 pediatric patients with fulminant liver failure, we reviewed the clinical and laboratory data of 12 (12.2%) who had fulminant WD. PELD-MELD, Child-Pugh scores and new Wilson indexes at the time of application were calculated. The prognoses were also recorded. Results: There were a total of 12 fulminant WD patients, 9 were female (75%). Mean age at time of arrival was 9.3+/-1.59 years (range: 7.3-12.5 y). 4 patients did not have findings of encephalopathy, while 2 patients had stage 1, 3 had stage 2 and 3 had stage 3 encephalopathy at the time of admission. 6 patients had ascites. Mean hemoglobin, white blood cell count and thrombocyte levels were 7.43+/-2.67 g/dL, 20,330+/-12,430/mm3 and 131,820+/-93,650/mm3, respectively. The liver function tests at the time of reference were; total bilirubin: 39.26+/-15.66 mg/dL, direct bilirubin: 27+/-11.76 mg/dL, AST: 513.66+/-943.6 U/L, ALT: 164.6+/-331.8 U/L, GGT: 78.4+/-71.8 U/L, ALP: 234+/-250.6 U/L, albumin 2.8+/-0.73 g/dL, prothrombin time 36.44+/-16.29 sec, INR 4+/-2.25. Mean creatinine value was 0.83+/-0.24 mg/dL, mean glomerular filtration rate was 77.66+/-64.84 ml/min/1.73 m2 and 5 patients had tubulopathy during follow up. 9 patients had low seruloplasmin levels. The seruloplasmin levels varied between 5.9-26 mg/dL (mean 13.8+/-7.4 mg/dL). 24-hour urine copper was measured in 4 patients and the mean level was 430+/-600 mugr/dL. The challenge test was performed in another 4 patients and mean urine copper was 3155+/-2490 mugr/dL. Mean PELD values, Child Pugh scores and new Wilson indexes were 32.1+/-11.5 (range: 16-48), 11.44+/-1.66 (range: 10-15) and 15.44+/-1.94 (range: 12-18), respectively. There was only 1 patient over age 11 with a MELD value of 40. Plasmapheresis was used in all patients, while D-penicillamine were also given in 3 patients, D-penicillamine, zinc and steroids to 2; trientine, zinc and steroids to 2 patients. 4 patients died, 6 underwent liver transplantation and 2 spontaneously survived. Histopathologic examinations of explant livers or postmortem liver necropsy samples were evaluated in 9 patients. 7 patients had cirrhosis, 1 had chronic active hepatitis and 1 had diffuse microvesicular steatosis. Mean tissue copper level was 440+/-347 mugr/g dry liver tissue. 5 patients who underwent liver transplant had living related donors and 1 patient had deceased donor. They were followed up for 9+/-3.3 years (range: 4.5-12 y) after transplantation. Conclusion: Fulminant WD is extremely fatal if liver transplant cannot be performed. Introduction of plasmapheresis and chelating therapy may be life-saving in low risk patients. Most patients have findings of cirrhosis on liver histopathological examination at time of arrival.",ascites;aspartate aminotransferase level;autopsy;chelation;child;Child Pugh score;chronic active hepatitis;clinical evaluation;clinical feature;deceased donor;explant;female;follow up;fulminant hepatic failure;glomerulus filtration rate;histopathology;human;human cell;human tissue;international normalized ratio;kidney tubule disorder;leukocyte count;liver cirrhosis;liver function test;liver graft;liver transplantation;living related donor;low risk patient;major clinical study;male;pediatric patient;plasmapheresis;prognosis;prothrombin time;provocation test;risk assessment;school child;steatosis;thrombocyte;urine;Wilson disease;albumin;bilirubin glucuronide;creatinine;endogenous compound;gamma glutamyltransferase;hemoglobin;penicillamine;steroid;trientine;zinc;conference abstract,"Ozcay, F.;Baris, Z.;Sezer, O. B.;Haberal, M.",2018,July,,0,0,
3346,Wilson's Disease: A case report. [Portuguese],"Objectives: This report describes a rare genetic disorder, called Wilson's Disease, inherited in an autosomal recessive form, with symptoms very easily confused with other diseases. The underlying cause of the clinical manifestations is the accumulation of copper in various compartments of the human body, especially in places such as liver, brain, kidneys and corneas, due to mutations in the ATP7B gene encoding Cu + 2 ATPase, a copper carrier protein which is located in the Golgi complex of hepatocytes. Liver changes may present as chronic hepatitis, cirrhosis and, more rarely, fulminant hepatitis. Neurological changes are variable, predominantly extrapyramidal symptoms, tremors, dystonia, dysarthria, mood changes, and psychiatric symptoms, if not treated, progressive decrease in intellectual capacity. One of the most extraordinary characteristics of this syndrome is the great variability of phenotypic manifestations in patients who have the same mutation. In the diagnosis of Wilson's disease, several biochemical parameters are analyzed: Serum ceruloplasmin, serum copper, urinary excretion of copper and hepatic copper concentration. In addition, an ophthalmologic examination is performed with Kayser-Fleischer rings observation. In order to complement and facilitate the diagnosis, genetic studies can be performed, since the symptoms and laboratory abnormalities can often be associated with other diseases. Treatment is based on the use of copper chelating drugs. D-penicillamine is the drug of choice, despite the risk of neurological worsening in up to 50% of patients and the various side effects associated with its use. Trientin and tetrathiomolybdate are alternative drugs, the latter being chosen for individuals with neurological symptoms. Zinc is indicated for asymptomatic or maintenance therapy. Early treatment prevents serious complications. Case report: A 14-year-old patient from Poco Fundo-MG sought medical attention because of frequent episodes of facial paralysis, especially in the mandibular region, leading to dysphagia and dysphonia, as well as irritability and gait abnormalities. She underwent magnetic resonance imaging (MRI), which showed ""symmetrical signal changes in the bilaterally striatum, with signs of edema of the caudate nuclei and caudate nuclei, and atrophy of the pale globes."" In view of the family history of Wilson's syndrome, a differential diagnosis was performed, by serum concentration of ceruloplasmin and serum and urinary copper, which showed typical changes in Wilson's syndrome and ocular biomicroscopy, which verified the presence of the Kayser-Fleischer ring. The patient did not present previous liver disease, showing that the disease does not always present as expected, and reflects the difficulty in establishing an early diagnosis that may prevent the emergence of the first symptoms. All patients with Wilson's syndrome require multidisciplinary care since it is a disease that can significantly affect various organs and systems. Copyright © 2018 Faculdade de Medicina de Ribeirao Preto - U.S.P. All rights reserved.",Cooper;Hepatolenticular Degeneration;Penicillamine;Wilson's Diseas;adolescent;article;brain atrophy/di [Diagnosis];brain edema/di [Diagnosis];brain radiography;Brazil;case report;caudate nucleus;ceruloplasmin blood level;clinical article;copper blood level;corpus striatum;differential diagnosis;dysphagia;dysphonia;facial nerve paralysis;family history;female;gait disorder;human;irritability;mandible;nuclear magnetic resonance imaging;slit lamp microscopy;urine level;Wilson disease/di [Diagnosis];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound],"Dos Santos Danziger Silverio, A.;Dos Santos Couto, T.;De Oliveira, J. M. P.",2018,January-March,http://dx.doi.org/10.11606/issn.2176-7262.v51i1p75-81,0,0,
3347,Challenges in diagnosis of wilson disease in a limited resource country,"Background: Wilson disease is a rare autosomal recessive condition caused by mutation in the ATP7B gene, with reduced excretion of Copper into bile, resulting accumulation of Copper in the liver, brain, kidneys, and eyes. The signs and symptoms of Wilson disease, such as hepatic dysfunctions, musculoskeletal manifestations, and neuropsychiatric features may difficult to distinguish from other diseases. Objective: To describe the challenges of the first diagnosed Wilson disease at Cipto Mangunkusumo Hospital. Case: A 13-year-old boy, born from non-consanguineous marriage, came with anemia one year ago. He was suspected with thalassemia, and then leukemia, but further diagnostic procedures showed negative results. He had a history of melena due to grade 3 esophageal varices and underwent variceal ligation. Six months later he was then referred to Nutrition and Metabolic Diseases Clinic with suspicion towards inherited metabolic diseases due to involuntary movements of the limbs and dysarthria. On physical examination, patient was severely malnourished with skin pigmentation, Kayser-Fleischer rings on both eyes, and hepatosplenomegaly. Laboratory findings revealed anemia, thrombocytopenia, and slightly elevated liver transaminases, normal serum electrolytes, plasma glucose and renal function. Brain MRI T2-weighted images revealed high signal hyperintensities in bilateral basal ganglia. Wilson disease was one of our differential diagnosis, therefore, we performed blood and urine sample abroad. Results showed low serum ceruloplasmin and elevated urinary copper. Based on the above investigations, we diagnosed Wilson disease and he was then treated with D-penicillamine, zinc, and diazepam. Conclusion: A suspicion is required to diagnose Wilson disease especially in a child with liver disease and neurological manifestations. It is still challenging to diagnose Wilson disease due to the lack of awareness and limited diagnostic methods in our country.",adolescent;awareness;basal ganglion;cancer patient;case report;ceruloplasmin blood level;child;clinical article;diagnosis;differential diagnosis;dysarthria;electrolyte blood level;esophagus varices;eye;glucose blood level;hepatosplenomegaly;human;human tissue;hypertransaminasemia;involuntary movement;kidney function;leukemia;ligation;limb;male;marriage;melena;nuclear magnetic resonance imaging;nutritional disorder;physical examination;skin pigmentation;thalassemia;thrombocytopenia;urine sampling;Wilson disease;diazepam;endogenous compound;penicillamine;zinc;conference abstract,"Pratita, W.;Rachmawati, N.;Sjarif, D. R.",2017,January-December,http://dx.doi.org/10.1177/2326409817722292,0,0,
3348,Clinically diagnosed late-onset fulminant Wilson's disease without cirrhosis: A case report,"A 64-year-old woman was referred to our hospital with jaundice of the bulbar conjunctiva and general fatigue. After admission, she developed hepatic encephalopathy and was diagnosed with fulminant hepatitis based on the American Association for the Study of Liver Disease (AASLD) position paper. Afterwards, additional laboratory findings revealed that serum ceruloplasmin levels were reduced, urinary copper levels were greatly elevated and Wilson's disease (WD)-specific routine tests were positive, but the Kayser-Fleischer ring was not clear. Based on the AASLD practice guidelines for the diagnosis and treatment of WD, the patient was ultimately diagnosed with fulminant WD. Then, administration of penicillamine and zinc acetate was initiated; however, the patient unfortunately died from acute pneumonia on the 28th day of hospitalization. At autopsy, the liver did not show a bridging pattern of fibrosis suggestive of chronic liver injury. Here, we present the case of a patient with clinically diagnosed late-onset fulminant WD without cirrhosis, who had positive disease-specific routine tests. Copyright © The Author(s) 2018. Published by Baishideng Publishing.",Copper;Fulminant hepatitis;Lateonset;Liver cirrhosis;Wilson's disease;acute liver failure;adult;anemia;anuria/su [Surgery];article;autopsy;bone marrow examination;case report;clinical article;continuous hemofiltration;death;eye jaundice;fatigue;female;fever;fulminant hepatic failure;hemophagocytic syndrome;hepatic encephalopathy;hepatosplenomegaly;human;liver necrosis;lobar pneumonia;middle aged;pancytopenia;platelet count;prothrombin time;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];ammonia/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];fresh frozen plasma;haptoglobin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];methylprednisolone/va [Intravaginal Drug Administration];methylprednisolone/vi [Intravitreal Drug Administration];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];zinc acetate/cb [Drug Combination];zinc acetate/dt [Drug Therapy],"Amano, T.;Matsubara, T.;Nishida, T.;Shimakoshi, H.;Shimoda, A.;Sugimoto, A.;Takahashi, K.;Mukai, K.;Yamamoto, M.;Hayashi, S.;Nakajima, S.;Fukui, K.;Inada, M.",2018,14 Jan,http://dx.doi.org/10.3748/wjg.v24.i2.290,0,0,
3349,Animal models of Wilson disease,"Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency. (Figure presented.). Copyright © 2018 International Society for Neurochemistry",Animal models;Wilson disease;Caenorhabditis elegans;disease model;Drosophila;gene function;gene therapy;genetic trait;human;kidney disease;Labrador retriever;liver disease;Long Evans cinnamon rat;neurologic disease;nonhuman;positron emission tomography-computed tomography;priority journal;review;rodent model;treatment response;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zebra fish;Menkes protein/ec [Endogenous Compound];n benzylglucamine n carbodithioic acid/dt [Drug Therapy];penicillamine/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];Atp7b knockout mouse;LPP rat;toxic milk mouse,"Reed, E.;Lutsenko, S.;Bandmann, O.",2018,August,http://dx.doi.org/10.1111/jnc.14323,0,0,
3350,High genetic carrier frequency of Wilson's disease in France: Discrepancies with clinical prevalence,"Background: Wilson's disease (WD) is a rare autosomal recessive metabolic disease caused by ATP7B gene mutations tat cause excessively high copper levels, particularly in the liver and brain. The WD phenotype varies in terms of its clinical presentation and intensity. Diagnosing this metabolic disorder is important as a lifelong treatment, based on the use of copper chelating agents or zinc salts, is more effective if it's started early. Worldwide prevalence of WD is variable, with an average of 1/30,000. In France, a recent study based on French health insurance data estimated the clinical prevalence of the disease to be around 3/200,000. Methods: To estimate the genetic prevalence of WD in France, we analysed the ATP7B gene by Next Generation Sequencing from a large French cohort of indiscriminate subjects. Results: We observed a high heterozygous carrier frequency of ATP7B in France. Among the 697 subjects studied, 18 variants classified as pathogenic or probably pathogenic were found at heterozygous level in 22 subjects (22 alleles/1394 alleles), yielding a prevalence of 0.032 or 1/31 subjects. Conclusions: This considerable and unexplained discrepancy between the heterozygous carrier frequency and the clinical prevalence of WD may be explained by the clinical variability, the incomplete penetrance and the existence of modifiers genes. It suggests that the molecular analysis of ATP7B should be interpreted with caution, always alongside copper assays (ceruloplasmin, relative exchangeable copper, 24 h-urinary copper excretion) with particular respect to exome sequencing. Copyright © 2018 The Author(s).",atp7b;Clinical prevalence;Copper;Epidemiology;Heterozygous carrier frequency;Wilson's disease;allele;article;cohort analysis;copper blood level;France;gene;gene frequency;genetic variability;heterozygosity;human;major clinical study;next generation sequencing;pathogenesis;prevalence;retrospective study;urinary excretion;whole exome sequencing;Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];chelating agent;zinc derivative;ATP7B gene,"Collet, C.;Laplanche, J. L.;Page, J.;Morel, H.;Woimant, F.;Poujois, A.",2018,10 Aug,http://dx.doi.org/10.1186/s12881-018-0660-3,0,0,
3351,Brain iron accumulation in Wilson's disease: A longitudinal imaging case study during anticopper treatment using 7.0T MRI and transcranial sonography,Level of Evidence: 5. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2018;47:282-285. Copyright © 2017 International Society for Magnetic Resonance in Medicine,iron accumulation;relaxometry;transcranial sonography;ultra-high field MRI;Wilson's disease;adult;article;ataxia;brain level;case report;caudate nucleus;cervical dystonia;chelation therapy;clinical article;clinical evaluation;controlled study;deterioration;disease association;drug dose increase;dysarthria;echography;enteric feeding;follow up;gene;gene mutation;genetic screening;globus pallidus;homozygosity;human;image analysis;male;neuroimaging;neurologic disease assessment;nuclear magnetic resonance imaging;patient monitoring;physiotherapy;priority journal;putamen;thalamus;three dimensional imaging;treatment outcome;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/rt [Radiotherapy];iron/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];zinc/dt [Drug Therapy];nuclear magnetic resonance scanner;real time ultrasound scanner;ATP7B gene;Unified Wilson Disease Rating Scale;Magnetom;MyLab Twice,"Dusek, P.;Skoloudik, D.;Maskova, J.;Huelnhagen, T.;Bruha, R.;Zahorakova, D.;Niendorf, T.;Ruzicka, E.;Schneider, S. A.;Wuerfel, J.",2018,January,http://dx.doi.org/10.1002/jmri.25702,0,0,
3352,A follow up study of symptomatic pediatric wilson disease from a non-transplant tertiary center,"Background and Aims: There is paucity of data on outcome of hepatic and neurological Wilson disease in children. Methods: Retrospective analysis of 90 patients of symptomatic Wilson disease was done (as per Ferenci criteria). Hepatic outcome was classified as resolution (R=normal LFT &asymptomatic), partial resolution (P=near normal LFT &asymptomatic), worsening or deterioration (W/D) and requiring transplant (OLT). Results: Hepatic (H) 75.5%, neurological (N) 16.6% and combined hepatic and neurological (H+N) 7.7% disease were seen at a mean age of 9.5 years in H &10.9 years in N &H &N. Mean duration of symptoms was 5.2 months in H &H+N and 8.76 months in N. 14.4% had history of consanguinity. 38.8% had family history. Hepatic manifestations were: Acute hepatitis-16%; acute liver failure-6.6%; acute on chronic liver failure-26.6%; compensated chronic liver disease (C CLD)-5.3%; decompensated cirrhosis (D CLD)-45%. 38.8% had varices &75% of H and 90.9% of H+N &N had KF rings. Mean ceruloplasmin was 9.89mg% in H and 6.6mg% in H+N &N. Mean Baseline 24h urine copper was 275mcg/24hours in H and 253 mcg/24h in H+N &N. Mean dry hepatic copper was 276mcg/g. 46.1% had histologic evidence of cirrhosis. Patients were treated with D penicillamine (D), Zinc (Z) or a combination of both (D+Z). Mean follow up was 86.6 months for 80 (89%) patients. Outcome of hepatic WD (H=68+H&N=7), are given (Fig. 1) R was attained in a mean of 21.8 months. Of patients with N (15), 2 (1 non compliant) patients had deterioration of neurological status. Conclusions: Hepatic presentation of WD is the commonest in children. Survival with native liver is 89.9% with optimum chelation therapy, and may take upto >1.5 yrs.",acute hepatitis;acute on chronic liver failure;chelation therapy;child;consanguinity;controlled study;decompensated liver cirrhosis;deterioration;family history;female;follow up;histopathology;human;human tissue;major clinical study;male;retrospective study;school child;urine;varicosis;Wilson disease;ceruloplasmin;endogenous compound;penicillamine;zinc;conference abstract,"Menon, J.;Sharma, S.;Venkatesh, V.;Lal, S. B.;Thapa, B. R.",2018,July,http://dx.doi.org/10.1016/j.jceh.2018.06.513,0,0,
3353,Study of clinical profile of wilson disease in a tertiary care center,"Background and Aims: To analyze clinical profile of patients with Wilson disease. Methods: The study was conducted in the Department of Medical Gastroenterology, Govt. Stanley medical college Chennai, from October 2017 May 2018. 16 Patients diagnosed to have Wilson disease were taken into the study.Wilson disease diagnosed based on modified Leipzig score using serum ceruloplasmin, 24h urine copper, K F ring, neurological features, liver biopsy etc. patients were analysed based on their clinical features at the time of presentation. Results: Majority of the patients were in the age group 15-30 years (56%). 9 patients were male and 7 were female. Majority of the patients presented with hepatic manifestations (68.7%)-jaundice was found in 63% patients and 50% patients had ascites. 25% patients had neuropsychiatric manifestations and 13% patients had both hepatic and neurologic features. KF ring present in 56% patients and all patients with neurological features had KF ring. 3 patients were asymptomatic and was diagnosed on family screening. 56% of patients were born out of consanguineous marriage. Conclusions: Consanguinity plays an important role in high frequency of disease among the affected family. Family screening is important for early diagnosis. Hepatic manifestations were found to be more common. Penicillamine and zinctherapy can effectivelytreatWilson disease with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage disease.",adolescent;ascites;ceruloplasmin blood level;clinical feature;consanguineous marriage;consanguinity;diagnosis;early diagnosis;female;gastroenterology;human;human tissue;jaundice;liver biopsy;liver transplantation;major clinical study;male;medical school;mental disease;nervous system;tertiary care center;urine;Wilson disease;endogenous compound;penicillamine;conference abstract,"Joseph, J.;Vinay, C.;Ms, R.",2018,July,http://dx.doi.org/10.1016/j.jceh.2018.06.509,0,0,
3354,A case of wilson disease presenting as acute pancreatitis,"Background: Wilson disease is a genetic disorder of copper metabolism with hepatic or neurological presentation. Wilson disease presenting as pancreatitis has been described previously in only two case reports and was attributed to either copper deposition in the pancreas or due to formation of biliary stones. Here we report a case of Wilson disease in a young adult presenting as acute pancreatitis and associated with gallstones. Case Summary: A 17 year old female presented with upper abdominal pain, jaundice since 2 days and non-billous vomiting for 1 day. She had no similar episodes in the past. Patient had no significant addictions and no contributory family or perinatal history. She had normal scholastic abilities. Clinical examination revealed presence of icterus, pallor and mild epigastric tenderness. Investigations showed Hemolytic anaemia, Deranged Liver function test in the form of mild hyperbilirubenimia andtransaminitis. Pancreatic enzymes were markedly elevated (amylase 816U/L/lipase 906U/L). Imaging showed features of Acute Interstitial Edematous Pancreatitis, Calculous Cholecystitis, Coarse Liver Parenchyma with Splenomegaly and Mild Ascites. She was treated for Biliary pancreatitis conservatively and showed good improvement. Work up for Chronic Liver Disease was done simultaneously which revealed low serum Ceruloplasmin level (0.05g/l), elevated 24h Urinary copper (1123.8mcg/day) and Positive KF Ring. After ascertaining diagnosis of Wilson disease, she was started on d-Penicillamine and Zinc Therapy. On followup her biochemical parameters improved with 24h urine copper gradually decreasing to 168mcg/day. Patient is completely asymptomatic at present and had no recurrence of pancreatitis. Conclusions: This case highlights an unusual presentation of wilson disease as biliary pancreatitis. Hence it brings into focus evaluation for liver diseases specially wilson disease in young individiuals with jaundice and pancreatitis.",acute hemorrhagic pancreatitis;addiction;adolescent;adult;ascites;bile duct stone;case report;ceruloplasmin blood level;cholecystitis;chronic liver disease;clinical article;clinical assessment;clinical examination;diagnosis;female;follow up;hemolytic anemia;human;human tissue;jaundice;liver function test;liver parenchyma;pallor;pancreatitis;protein expression;relapse;splenomegaly;upper abdominal pain;urine;vomiting;Wilson disease;young adult;amylase;endogenous compound;pancreas enzyme;penicillamine;triacylglycerol lipase;zinc;conference abstract,"Tarkeshwari, R. Y.;Shanmuganathan, S.;Panchapakesan, G.",2018,July,http://dx.doi.org/10.1016/j.jceh.2018.06.501,0,0,
3355,Stroke in a young patient with wilson's disease: The spectre of 're balanced hemostasis',"Background: Coagulopathy is an essential component of the liver cell failure and reflects the central role of liver function in hemostasis. Case Summary: We present a seven-year old boy, a known case Wilson's disease who presented with jaundice and abdominal distension for two weeks with history of repeated episodes of hypoglycemia for last five days. He was on Penicillamine 500mg thrice daily. On examination he was found to have chronic liver disease, decompensated with grade I hepatic encephalopathy and minimal ascites. Laboratory investigations showed thrombocytopenia (64,000/mm3), Blood sugar of 52mg/dl, Serum albumin; 2.5mg/dl, Bilirubin; 17mg/dl, Serum Alanine transaminase; 52IU/L, Aspartate transaminase; 153IU/L, Alkaline phosphatase; 211IU/L, and international nor malized ratio of 3.1. The patient was listed on priority for liver transplant with PELD value of 32 and Na MELD of 30, the donor being his mother. However, within 7 days of listing the patient developed sudden onset of de-cerebrate posturing. CT scan of head showed acute frontal lobe venous infarct with midline shift. His condition deteriorated rapidly and he died on the next day likely due to cerebral herniation, despite all critical care measures. Conclusions: The above case depicts the dynamic state of ""rebalanced hemostatic"" in a patient with liver cirrhosis with significant coagulopathy. The risk for cerebrovascular events especially infarcts in cirrhosis has not been clearly determined. The restored balance of hemostasis afforded by concomitant reduction of procoagulant and anti coagulant factors might explain the arterial and venous thrombotic events, challenging the old dogma/paradox of increased bleeding in patients with liver cirrhosis.",abdominal distension;artery;ascites;bleeding;brain hernia;case report;cerebrovascular accident;child;chronic liver disease;clinical article;female;frontal lobe;glucose blood level;head;hemostasis;hepatic encephalopathy;human;human tissue;hypoglycemia;infarction;intensive care;jaundice;liver cirrhosis;liver graft;male;school child;thrombocytopenia;vein thrombosis;Wilson disease;X ray computed tomography;alanine aminotransferase;alkaline phosphatase;anticoagulant agent;aspartate aminotransferase;bilirubin;endogenous compound;penicillamine;procoagulant;serum albumin;sodium;conference abstract,"Javid, K.;Cg, S.;Khan, J.;Ts, R. K.;Reddy, R.",2018,July,http://dx.doi.org/10.1016/j.jceh.2018.06.366,0,0,
3356,Update on Wilson disease: focus on WTX-101,"Wilson disease (WD) is a rare genetic disorder of copper metabolism. Treatment is lifelong with the aim of restoring copper homeostasis. The current treatments are limited by multiple daily dosing and side effects, as well as a rare but serious risk of neurological deterioration on initiation of chelation therapy. Excess free copper is thought to be responsible for copper toxicity and early neurological deterioration. Bis-choline tetrathiomolybdate (WTX-101) is currently one of the emerging novel therapies appearing to fulfill an unmet need by providing an option for single daily dosing and lack of significant unwanted effects. It also appears to be at low risk of causing early neurologic deterioration. WTX-101 reduces free copper levels by forming a tight complex with copper. A recent phase II study has demonstrated promising results on copper control and clinical symptoms in newly diagnosed WD patients. A phase III study is underway and aims to confirm its safety and efficacy. Copyright © 2018 Clarivate Analytics.",Bis-choline tetrathiomolybdate;Wilson disease;wtx-101;article;chelation therapy;copper blood level;disease exacerbation;drug efficacy;drug mechanism;drug safety;human;mental disease/si [Side Effect];nonhuman;phase 2 clinical trial (topic);randomized controlled trial (topic);single drug dose;Wilson disease/dt [Drug Therapy];central nervous system agents/do [Drug Dose];central nervous system agents/dt [Drug Therapy];central nervous system agents/pk [Pharmacokinetics];central nervous system agents/pd [Pharmacology];chelating agent/ae [Adverse Drug Reaction];chelating agent/dt [Drug Therapy];copper/ec [Endogenous Compound];tetrathiomolybdic acid/do [Drug Dose];tetrathiomolybdic acid/dt [Drug Therapy];tetrathiomolybdic acid/pk [Pharmacokinetics];tetrathiomolybdic acid/pd [Pharmacology];unclassified drug;bischoline tetrathiomolybdate/do [Drug Dose];bischoline tetrathiomolybdate/dt [Drug Therapy];bischoline tetrathiomolybdate/pk [Pharmacokinetics];bischoline tetrathiomolybdate/pd [Pharmacology];wtx 101,"Camarata, M. A.;Ala, A.;Schilsky, M. L.",2018,,http://dx.doi.org/10.1358/dof.2018.043.07.2819432,0,0,
3357,Mowat-Wilson syndrome presenting with fever-associated seizures,"Mowat-Wilson syndrome (MWS) is a disorder caused by mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. Diagnosis of MWS can be challenging to neurologists, because its manifestations are diverse and the spectrum of genetic mutations are broad. Here, we describe two patients with MWS who initially showed atypical forms of fever-triggered seizures during childhood. Both had characteristic facial features, cognitive impairment, and genito-urinary anomalies consistent with MWS. By performing targeted next-generation sequencing (NGS) using a gene panel for epilepsy, we were able to identify a nonsense mutation (c.1965C>A) in the ZEB2 gene of one patient and a frameshift mutation (c.2348dupC) in the other patient. Fever-induced seizures can be presenting signs of MWS. MWS should be considered in the differential diagnosis of fever-induced seizures, especially when the patient has distinctive facial features and multiple anomalies, including cardiac, genito-urinary, and eye defects. Copyright © 2017 Epileptic Disorders",epilepsy;febrile seizure;Mowat-Wilson syndrome;next-generation sequencing;zeb2;birth weight;body weight;case report;child;clinical article;cognitive defect;cryptorchism;developmental delay;differential diagnosis;electroencephalogram;epileptic discharge;facies;febrile convulsion;female;frameshift mutation;gene;genetic screening;human;hydrocele;hydronephrosis;hypertelorism;male;multiplex ligation dependent probe amplification;neurologic examination;next generation sequencing;nonsense mutation;note;nuclear magnetic resonance imaging;outpatient department;preschool child;stop codon;telecanthus;thrombocytopenia;tonic clonic seizure;ureter;urogenital tract disease;Wilson disease;levetiracetam;valproic acid;zinc finger E box binding homeobox 2/ec [Endogenous Compound];SCN1A gene,"Seo, S. E.;Kim, S. H.;Lee, S. T.;Choi, J. R.;Lee, J. S.;Kim, H. D.;Kang, H. C.",2017,December,http://dx.doi.org/10.1684/epd.2017.0949,0,0,
3358,WTX101-A novel copper-protein-binding agent for Wilson Disease demonstrates long-term neurological improvement in an ongoing extension of a Phase-2 study (WTX101-201),"Background and aims: WTX101 (bis-choline tetrathiomolybdate) is a first-in-class copper-protein-binding agent that reduces plasma non-ceruloplasmin bound copper (NCC) by forming tripartite complexes with albumin and increases biliary copper excretion. Here, we present preliminary 72-week data from the ongoing extension of a Phase-2 study in patients with Wilson Disease (WD). Methods: All 22 patients who completed the 24-week openlabel, single-arm study opted to continue once-daily WTX101 treatment in the extension. Assessments up to 72 weeks included disability and neurological status using the Unified Wilson Disease Rating Scale (UWDRS), copper control, hepatic status and safety. Results: At study entry, 86% of patients had various degrees of WD-related neurological symptoms. From baseline to week 72, mean (SD) UWDRS disability score improved from 6.6 (10.0) to 1.2 (2.1) and neurological score from 22.8 (21.0) to 9.9 (10.7). UWDRS neurological score improved by >=4 points in 12 patients, stabilised (+/-3 points) in 5 patients and worsened by >=4 points in 2 patients . Mean (SD) NCC level corrected for copper in tripartite complexes was 3.6 (2.1) muM at baseline and decreased to 0.5 (0.7) muM at week 72. Liver function tests and Model for End-Stage Liver Disease (MELD) score improved or remained unchanged at week 72. Two discontinuations were considered unrelated to WTX101 treatment. Conclusion: Once-daily WTX101 treatment improved neurological status and disability, and controlled free copper in patients with WD over 72 weeks. WTX101 was generally well tolerated and, together with its simplified dosing, WTX101 has the potential to address unmet needs in WD.",adult;case report;clinical article;disability;drug safety;female;human;human tissue;liver function test;male;Model For End Stage Liver Disease Score;phase 2 clinical trial;rating scale;Wilson disease;conference abstract,"Czlonkowska, A.;Schilsky, M.;Askari, F.;Ferenci, P.;Bronstein, J.;Bega, D.;Ala, A.;Nicholl, D.;Weiss, K. H.",2018,June,,0,0,
3359,Metallothionein is elevated in liver and duodenum of Atp7b<sup>(-/-)</sup> mice,"Different mutations in the copper transporter gene Atp7b are identified as the primary cause of Wilson's disease. These changes result in high copper concentrations especially in the liver and brain, and consequently lead to a dysfunction of these organs. The Atp7<sup>(-/-)</sup> mouse is an established animal model for Wilson's disease and characterized by an abnormal copper accumulation, a low serum oxidase activity and an increased copper excretion in urine. Metallothionein (MT) proteins are low molecular weight metal-binding proteins and essential for the zinc homeostasis but also play a role for the regulation of other metals, e.g. copper. However the molecular mechanisms of MT in regard to Atp7b remain still elusive. In this study we investigate the expression of MT in the liver and duodenum of Atp7b<sup>(-/-)</sup> mice and wildtype mice. Hepatic and duodenal expression of MT was measured by real-time reverse transcription-polymerase chain reaction and post-translational expression was analyzed by immunoblot and immunofluorescence. Expression of MT in liver und duodenum was significantly higher in Atp7b<sup>(-/-)</sup> mice than in controls. Hepatic and duodenal copper, iron and zinc content were also studied. Compared to control hepatic copper and iron content was significantly higher while hepatic zinc content was significantly lower in Atp7b<sup>(-/-)</sup> mice. In the duodenum copper and zinc content of Atp7b<sup>(-/-)</sup> mice was significantly lower than in controls. Duodenal iron content was also lower in Atp7b<sup>(-/-)</sup> mice, but did not reach statistical significance. The results of our study suggest that metallothionein is elevated in the liver and duodenum of Atp7b<sup>(-/-)</sup> mice. Copyright © 2018, The Author(s).",Atp7b;Copper;Duodenum;Liver;Metallothionein;Wilson's disease;article;atomic absorption spectrometry;comparative study;controlled study;enzyme activity;gene mutation;immunoblotting;immunofluorescence;metal binding;molecular weight;mouse;nonhuman;protein binding;real time polymerase chain reaction;reverse transcription polymerase chain reaction;RNA isolation;Western blotting;Wilson disease;zinc homeostasis;cadmium;iron;metallothionein/ec [Endogenous Compound];Wilson disease protein/ec [Endogenous Compound];zinc,"Zhang, C. C.;Volkmann, M.;Tuma, S.;Stremmel, W.;Merle, U.",2018,01 Aug,http://dx.doi.org/10.1007/s10534-018-0110-x,0,0,
3360,Wilson disease and related copper disorders,"Copper is a required cofactor for enzymes in critical metabolic pathways. Mutations in copper metabolism genes or abnormalities in copper metabolism result in disease from copper excess or deficiency. Wilson disease (WD) is an autosomal-recessive disease caused by mutations in the ATP7B gene which encodes a copper-transporting ATPase. Over 500 different WD mutations throughout the ATP7B gene have been described, most of which are missense mutations. Mutations in both ATP7B alleles result in abnormal copper metabolism and subsequent toxic accumulation of copper. The clinical manifestations of neurologic WD include variable combinations of dysarthria, dystonia, tremor, and choreoathetosis. Misdiagnosis and delay in treatment are clinically relevant because untreated WD progresses to hepatic failure or severe neurologic disability and death. Treatment can prevent and cure WD. Mutations in a second, closely related copper-transporting ATPase, ATP7A, cause a spectrum of copper deficiency disorders that include Menkes disease, occipital horn syndrome, and ATP7A-related distal motor neuropathy. Two important, nongenetic causes of copper deficiency myeloneuropathy are copper deficiency following gastric bypass or due to excess zinc ingestion, both of which can cause a myeloneuropathy similar to vitamin B12 deficiency. Copper deficiency following gastric bypass is preventable, and identification and elimination of the excess zinc source, most commonly dental cream, can result in recovery. Copyright © 2018 Elsevier B.V. All rights reserved.","atp7a;ATP7A-related distal motor neuropathy;atp7b;copper;copper deficiency myeloneuropathy;Menkes disease;occipital horn syndrome;Wilson disease;drug effect;genetics;human;metabolism;mutation;pathophysiology;physiology;stomach;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];copper/ad [Drug Administration];copper exporting adenosine triphosphatase;deficiency;ATP7B protein, human","Lorincz, M. T.",2018,,http://dx.doi.org/10.1016/B978-0-444-63233-3.00018-X,0,0,
3361,Wilson disease with hepatic impairment and thrombocytopenia: A case report,"Introduction: Wilson disease is a rare autosomal recessive disorder. The Case report describes the penicillamine induced thrombocytopenia. Case Report: A 14-year-old girl presented with previously diagnosed with Wilson disease treated with penicillamine and pyridoxine. Complaints of dyskine-sia, slurred speech, severe hyperbilirubinemia and prominent extrapyrami-dal features consisting of the rigidity, tremors and ophthalmic examination of her eyes reveal the Kayser-Fleischer ring and sunflower cataract and low blood count. Conclusion: Wilson disease is a rare inherited disorder. Approximately 30% of the patient cannot tolerate penicillamine due to early hypersensitivity or bone marrow suppression or renal failure occurs due to the failure of therapy. Hence zinc is considered an alternative therapy for pediatric patients. Copyright © 2018 EManuscript Technologies. All rights reserved.",Hepatic impairment;Penicillamine;Thrombocytopenia;Wilson disease;Zinc;adolescent;anemia/di [Diagnosis];aphasia/di [Diagnosis];article;case report;cataract/di [Diagnosis];clinical article;clinical feature;disease severity;dysphagia/di [Diagnosis];eosinophilia/di [Diagnosis];extrapyramidal syndrome/di [Diagnosis];eye examination;female;gastrocnemius muscle;human;hyperbilirubinemia/di [Diagnosis];leukopenia/di [Diagnosis];liver failure/di [Diagnosis];muscle rigidity/di [Diagnosis];physical examination;priority journal;splenomegaly/di [Diagnosis];thrombocytopenia/di [Diagnosis];urinalysis;urine sampling;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];penicillamine/dt [Drug Therapy];pyridoxine/dt [Drug Therapy],"Karthickeyan, K.;Reddy, C. M.;Mohamed, J. B. N.;Vaibhavi, K.",2018,July-September,http://dx.doi.org/10.5530/jyp.2018.10.82,0,0,
3362,CCDC115-CDG: A new rare and misleading inherited cause of liver disease,"Congenital disorders of glycosylation (CDG) linked to defects in Golgi apparatus homeostasis constitute an increasing part of these rare inherited diseases. Among them, COG-CDG, ATP6V0A2-CDG, TMEM199-CDG and CCDC115-CDG have been shown to disturb Golgi vesicular trafficking and/or lumen pH acidification. Here, we report 3 new unrelated cases of CCDC115-CDG with emphasis on diagnosis difficulties related to strong phenotypic similarities with mitochondriopathies, Niemann-Pick disease C and Wilson Disease. Indeed, while two individuals clinically presented with early and severe liver fibrosis and cirrhosis associated with neurological symptoms, the other one ""only"" showed isolated and late severe liver involvement. Biological results were similar to previously described patients, including hypercholesterolemia, elevated alkaline phosphatases and defects in copper metabolism. CDG screening and glycosylation study finally led to the molecular diagnosis of CCDC115-CDG. Besides pointing to the importance of CDG screening in patients with unexplained and severe liver disease, these reports expand the clinical and molecular phenotypes of CCDC115-CDG. The hepatic involvement is particularly addressed. Furthermore, hypothesis concerning the pathogenesis of the liver disease and of major biological abnormalities are proposed. Copyright © 2018 Elsevier Inc.",ccdc115;cdg;Copper;Glycosylation;Liver fibrosis;Liver steatosis;adolescent;alanine aminotransferase blood level;alkaline phosphatase blood level;article;aspartate aminotransferase blood level;body dysmorphic disorder;capillary electrophoresis;case report;cell vacuole;ceruloplasmin blood level;cholangiocyte;clinical article;congenital disorder of glycosylation;copper blood level;copper metabolism;exon;fatty liver;female;gene mutation;gene sequence;hepatic portal vein;hepatomegaly;hepatosplenomegaly;human;human tissue;hypercholesterolemia;liver biopsy;liver cell;liver disease/et [Etiology];male;matrix assisted laser desorption ionization time of flight mass spectrometry;missense mutation;nonsense mutation;pathogenesis;phenotype;portal hypertension;priority journal;two dimensional electrophoresis;alanine aminotransferase/ec [Endogenous Compound];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];glycogen/ec [Endogenous Compound];penicillamine;protein/ec [Endogenous Compound];ubiquinol cytochrome c reductase/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound];Coiled Coil Domain Containing 115 protein/ec [Endogenous Compound],"Girard, M.;Poujois, A.;Fabre, M.;Lacaille, F.;Debray, D.;Rio, M.;Fenaille, F.;Cholet, S.;Ruel, C.;Causse, E.;Selves, J.;Bridoux-Henno, L.;Woimant, F.;Dupre, T.;Vuillaumier-Barrot, S.;Seta, N.;Alric, L.;de Lonlay, P.;Bruneel, A.",2018,July,http://dx.doi.org/10.1016/j.ymgme.2018.05.002,0,0,
3363,Cerebral metal accumulation and neurodegenerative disorders-causal relationship?,"Metal ions are necessary for life as cofactors of various metalloproteins, but they are toxic in excess. Based on their abundance in human body, biogenic metals can be divided into bulk (e.g. calcium, magnesium), trace (e.g. iron, zinc), and ultra-trace (e.g. manganese, copper, cobalt, molybdenum) elements. Several other metals such as mercury or lead can enter the brain and induce neurotoxicity. Mutations in proteins involved in metal homeostasis cause systemic metal accumulation disorders with tissue metal concentration increased by a factor of 5 or more. These genetic disorders may be regarded as model diseases for metal neurotoxicity. Mutation in ATP7B copper transporter causes Wilson disease, mutations in SLC30A10 and SLC39A14 cause manganese transporter deficiencies, and mutations in genes coding for ceruloplasmin and ferritin lead to neurodegeneration with brain iron accumulation. Environmental metal exposure may also result in distinct neuropathology with severe clinical phenotype as has been documented for mercury in Minamata Bay, Japan during 1930-1960 and for manganese during the epidemic of intravenous methcatinon abuse in eastern Europe in 1990-2010. Disturbances of cerebral metal homeostasis, namely of iron, copper, and manganese have been also found in common sporadic neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulated transition metals in brain may contribute to neurodegeneration by mediating oxidative stress, altering enzymatic functions, inducing protein aggregation, and triggering neuronal death. The outstanding questions for research in metallo-biology of neurodegeneration are 1) whether low-level environmental metal exposure may induce neurotoxicity, and 2) whether correction of impaired metal homeostasis, e.g. by chelation, could have neuroprotective effect.",Alzheimer disease;animal experiment;animal model;brain;chelation;death;drug therapy;Eastern Europe;enzyme activity;epidemic;gene mutation;genetic susceptibility;homeostasis;Japan;nerve degeneration;neuropathology;neurotoxicity;nonhuman;oxidative stress;Parkinson disease;phenotype;protein aggregation;Wilson disease;calcium;ceruloplasmin;cobalt;endogenous compound;ferritin;iron;magnesium;manganese;mercury;metal ion;molybdenum;Wilson disease protein;zinc;conference abstract,"Dusek, P.",2018,July,http://dx.doi.org/10.1002/2211-5463.12449,0,0,
3364,Wilson's disease: The eponymous eminence of careful cognizance!,"Hepatolenticular degeneration (Wilson's disease) is a rare autosomal disorder with an identified genetic abnormality identified on chromosome arm 13q and a resultant defect in the hepatic copper-transporting ATPase gene (ATP7B) [1]. The core abnormality is a dysfunction of copper metabolism with abnormal biliary excretion of copper and the resultant accumulation of this toxic chemical in classically identified structures (i.e. cornea, liver, brain, others) [1], [2]. Various perplexing presentations can be seen making an accurate diagnosis challenging; classically there is the triad of liver disease, neuropsychiatric presentations and Kayser-Fleischer rings in the cornea [1], [2], [3], [4], [5], [6]. The Kayser-Fleischer rings are copper deposits in the cornea in which an ophthalmologic examination reveals a golden discoloration in the membrane of Descemet at the limbic regions. The hepatic presentation can appear similar to that of chronic active hepatitis including cirrhosis [2]. The neuropsychiatric presentations can include symptoms suggestive of schizophrenia, bipolar disorders or Parkinsonism with basal ganglia involvement. Also, there can be incoordination, arm ""wing-beating"", dystonia and/or dystonic posturing. Dysarthria is noted in most and dysphagia can also occur. Clinical confusion is noted in the encephalopathy seen in this condition, whether it is due to liver failure or copper toxicity itself [5]. Diagnosis involves testing of blood (including low serum ceruloplasmin) as well as urine (including increased urinary copper levels) along with a liver biopsy (revealing increased copper deposits) and genetic testing [2], [6]. It is a fatal disease without treatment that includes early diagnosis, placing the patient on a low copper diet (avoiding copper utensils for cooking) and utilization of copper chelation with D-penicillamine or trientine as well as zinc supplements [1], [2], [3], [4], [5], [6]. Liver transplantation has been used for resistant cases including liver failure [7]. Copyright © 2018 Walter de Gruyter GmbH, Berlin/Boston.",adult;article;basal ganglion;biliary excretion;bipolar disorder;ceruloplasmin blood level;chelation;chromosome arm;chronic active hepatitis;congenital malformation;controlled study;cooking;coordination disorder;copper metabolism;cornea;diagnosis;diet;dysarthria;dysphagia;dystonia;early diagnosis;genetic screening;human;human tissue;limbic cortex;liver biopsy;liver cirrhosis;liver failure;liver transplantation;membrane;ophthalmology;parkinsonism;schizophrenia;urine;Wilson disease;wing;copper exporting adenosine triphosphatase;endogenous compound;penicillamine;toxic substance;trientine;Wilson disease protein;zinc,"Greydanus, D. E.;Merrick, J.",2018,,http://dx.doi.org/10.1515/ijamh-2018-0113,0,0,
3365,Long-term evaluation of urinary copper excretion and non-caeruloplasmin associated copper in Wilson disease patients under medical treatment,"Objective: Urinary copper excretion rates and non-caeruloplasmin associated copper concentrations are increased in patients with Wilson disease. However, there is little literature describing the monitoring of these parameters over the long term. Methods: This is a monocentric retrospective study including data collected between 2003 and 2015 from 321 patients with Wilson disease by chart review. The patients were under therapy with D-penicillamine, trientine, or zinc. 24-h urinary copper excretion rates, non-caeruloplasmin associated copper, and total serum copper concentrations were determined at the start of therapy, as well as 6, 12, 18, 24, 36, and >= 60 months after the start of therapy. For patients taking chelating agents, all parameters were measured while under continued therapy, as well as after a 48-h dose interruption. A mathematical formula to predict 24-h urinary copper excretion rates under different therapies was established. Results: In all treatment groups, urinary copper excretion rates decreased over time, but the inter-individual variation of the results was high. Non-caeruloplasmin associated copper concentrations tended to decline over time, but with a higher variation of results than that observed for urinary copper excretion rates. Conclusion: Due to their variability, urinary copper excretion rates and serum copper concentrations are less than ideal parameters by which to monitor the benefit of a copper-reducing therapy. Urinary copper excretion rates seem to be more suitable than non-caeruloplasmin associated copper concentrations for this purpose. Copyright © 2018 SSIEM",Chelator;Long term;Non-caeruloplasmin associated serum copper;Urinary copper excretion;Wilson disease;Zinc;adult;article;controlled study;copper blood level;excretion;female;human;human tissue;major clinical study;male;medical record review;retrospective study;penicillamine;trientine,"Pfeiffenberger, J.;Lohse, C. M.;Gotthardt, D.;Rupp, C.;Weiler, M.;Teufel, U.;Weiss, K. H.;Gauss, A.",2018,20 Jun,http://dx.doi.org/10.1007/s10545-018-0218-8,0,1,
3366,Wilson disease and lupus nephritis: is it coincidence or a true association?,"A 12-year-old girl born to third-degree consanguineous parents presented with recurrent episodes of haematuria for 8 months in association with peri-orbital and lower limb oedema for 20 days. There was no jaundice, hepatomegaly or neurological abnormality at presentation. An older brother had died following jaundice at 10 years of age. Urinalysis showed multiple dysmorphic erythrocytes without proteinuria and there was leucopenia, thrombocytopenia and hypo-albuminaemia (23 g/L). C<inf>3</inf> component of complementaemia was low and anti-nuclear antibodies and anti-double-stranded DNA antibodies were strongly positive by immunofluorescence. Systemic lupus erythematosus (SLE) was considered but the severe hypo-albuminaemia was unexplained. During the pre-renal biopsy work-up, a deranged coagulation profile with raised transaminases prompted evaluation for chronic liver disease which culminated in the diagnosis of Wilson disease. Treatment with penicillamine and immunosuppressants was initiated, but there was neurological deterioration on Day 30 of admission and she died owing to worsening liver failure on the Day 41. Post-mortem liver biopsy demonstrated cirrhosis and post-mortem renal biopsy showed features of class-II lupus nephritis. Auto-immune antibodies and autoimmune disorders have been reported in Wilson disease and there are anecdotal reports of an association of SLE with Wilson disease. However, this case is unique in that lupus nephritis was the presenting manifestation before Wilson disease was diagnosed. The underlying pathophysiological mechanisms of this association requires further research. Copyright © 2018 Informa UK Limited, trading as Taylor & Francis Group",glomerulonephritis;haematuria;Systemic lupus erythematosus;Wilson disease;article;brother;case report;child;chronic liver disease;clinical article;congenital malformation;diagnosis;edema;female;girl;hematuria;hepatomegaly;human;human cell;hypoalbuminemia;immunofluorescence;jaundice;kidney biopsy;leukopenia;liver biopsy;liver cirrhosis;liver failure;lower limb;lupus erythematosus nephritis;male;orbit;proteinuria;school child;thrombocytopenia;urinalysis;aminotransferase;antinuclear antibody;double stranded DNA antibody;endogenous compound;immunosuppressive agent;penicillamine,"Pradhan, S.;Krishnamurthy, S.;Jagadisan, B.;Rajesh, N. G.;Kaliaperumal, S.;Ramasamy, S.;Subramanian, N.",2018,13 Mar,http://dx.doi.org/10.1080/20469047.2018.1443411,0,0,
3367,Metabolic disposition of WTX101 (bis-choline tetrathiomolybdate) in a rat model of Wilson disease,"1. WTX101 (bis-choline tetrathiomolybdate) is an investigational copper (Cu)-protein-binding agent developed for the treatment of Wilson disease (WD), a rare genetic disorder caused by mutations in the ATP7B Cu-transporter and resulting in toxic Cu accumulation. 2. Mass balance of a single intravenous WTX101 dose, measured as molybdenum (Mo), was assessed over 168h in control (Long Evans Agouti [LEA]) and Long-Evans Cinnamon (LEC) rats, a WD model. 3. In LEC rats, Mo was partially excreted (up to 45%); 29% by renal clearance, and faecal clearance, still ongoing at 168h, accounted for 16%. In contrast, in LEA rats, Mo was almost fully excreted (~87%); 79% was renally cleared with only 7% faecal excretion. 4. In LEC rats, the proportion of faecal to renal Mo excretion was enhanced (4:6) compared to controls (1:9). 5. Substantially more Mo was found in LEC liver and kidney compared with LEA tissues, in line with tissue Cu distribution. 6. These findings are consistent with the WTX101 mechanism of action: in the WD model, excess Cu is removed from hepatic metallothionein and retained within the stable tetrathiomolybdate-Cu-albumin tripartite complex, preventing tetrathiomolybdate degradation and resulting in less urinary elimination and greater faecal excretion than in controls. Copyright © 2018 Informa UK Limited, trading as Taylor & Francis Group",copper;hepatobiliary elimination;inbred Long-Evans Cinnamon;rats;Tetrathiomolybdate;Wilson disease;animal experiment;animal model;article;biliary excretion;controlled study;degradation;drug toxicity;feces;gene mutation;genetic susceptibility;liver;Long Evans cinnamon rat;nonhuman;pharmacokinetics;rat;rat model;renal clearance;albumin;choline tetrathiomolybdate;endogenous compound;metallothionein;molybdenum;tetrathiomolybdic acid;Wilson disease protein,"Plitz, T.;Boyling, L.",2018,27 Feb,http://dx.doi.org/10.1080/00498254.2018.1443352,0,0,
3368,Reversible pancytopenia caused by severe copper deficiency in a patient with Wilson disease,,adult;ataxia;bone marrow biopsy;case report;ceruloplasmin blood level;chelation therapy;clinical article;copper deficiency/dt [Drug Therapy];copper deficiency/su [Surgery];disease course;dyserythropoiesis;dystonia;female;hemoglobin blood level;human;human tissue;leukocyte count;limb deformity;limited mobility;neutropenia/dt [Drug Therapy];neutrophil count;note;occult blood test;onset age;pancytopenia;tremor;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];zinc blood level;baclofen/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];chelating agent/dt [Drug Therapy];diazepam/dt [Drug Therapy];gluconate copper/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];lactulose/dt [Drug Therapy];trihexyphenidyl/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Mohamed, M.;Johnston, A.;Cross, A. M.;Sharma, A.",2018,02 Jul,http://dx.doi.org/10.5694/mja17.00831,0,0,
3369,WTX101 - an investigational drug for the treatment of Wilson disease,"Introduction: Wilson disease (WD) is a genetic disorder in which excess toxic copper accumulates in the liver, brain, and other tissues leading to severe and life-threatening symptoms. Copper overload can be assessed as non-ceruloplasmin-bound copper non-ceruloplasmin-bound copper (NCC) in blood. Current therapies are limited by efficacy, safety concerns, and multiple-daily dosing. Areas covered: This article reviews the literature on WTX101 (bis-choline tetrathiomolybdate), an oral first-in-class copper-protein-binding agent in development for the treatment of WD. Expert opinion: In a proof-of-concept phase II trial, once-daily WTX101 over 24 weeks rapidly lowered NCC levels and this was accompanied by improved neurological status without apparent initial drug-induced paradoxical worsening, reduced disability, stable liver function, with a favorable safety profile. WTX101 directly removes excess copper from intracellular hepatic copper stores and also forms an inert tripartite complex with copper and albumin in the circulation and promotes biliary copper excretion. These mechanisms may explain the rapid biochemical and clinical improvements observed. A phase III trial of WTX101 is ongoing and results are eagerly awaited to confirm if WTX101 can improve the treatment of this devastating disease. Copyright © 2018 Informa UK Limited, trading as Taylor & Francis Group",Chelation therapy;copper;tetrathiomolybdate;Wilson disease;article;controlled study;disability;drug safety;excretion;human;liver function;phase 2 clinical trial;phase 3 clinical trial;proof of concept;albumin;choline tetrathiomolybdate;endogenous compound;tetrathiomolybdic acid,"Weiss, K. H.;Czlonkowska, A.;Hedera, P.;Ferenci, P.",2018,09 Jun,http://dx.doi.org/10.1080/13543784.2018.1482274,0,0,
3370,Zinc monotherapy for young children with presymptomatic Wilson disease: A multicenter study in Japan,"Background and Aim: Few studies of zinc monotherapy for presymptomatic Wilson disease have focused on young children. We therefore evaluated long-term efficacy and safety of zinc monotherapy for such children and established benchmarks for maintenance therapy. Methods: We retrospectively and prospectively examined children under 10 years old with presymptomatic Wilson disease who received zinc monotherapy from time of diagnosis at 12 participating pediatric centers in Japan. Results: Twenty-four patients met entry criteria. Aspartate aminotransferase and alanine aminotransferase decreased significantly beginning 1 month after initiation of treatment and usually remained under 50 U/L from 1 to 8 years of treatment. Twenty four-hour urinary copper decreased significantly at 6 months and usually remained under 75 mug/day and between 1 and 3 mug/kg/day for the remainder of the study. All patients continued to take zinc, and none became symptomatic. In patients under 6 years old who received 50 mg/day of zinc as an initial dose, aspartate aminotransferase and alanine aminotransferase significantly decreased at 1 month after initiation of treatment, as did gamma-glutamyltransferase and 24-h urinary copper at 6 months. Conclusions: To our knowledge, this is the first multicenter study of zinc monotherapy for young children with presymptomatic Wilson disease. Such monotherapy proved highly effective and safe. Maintaining normal transaminase values (or values under 50 U/L when normalization is difficult) and 24-h urinary copper excretion between 1 and 3 mug/kg/day and under 75 mug/day is a reasonable goal. An initial dose of 50 mg/day is appropriate for patients under 6 years old. Copyright © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd",presymptomatic;Wilson disease;young children;zinc;article;aspartate aminotransferase blood level;asymptomatic disease/dt [Drug Therapy];child;clinical article;drug efficacy;drug safety;gamma glutamyl transferase blood level;human;monotherapy;multicenter study;priority journal;prospective study;retrospective study;urinary excretion;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];copper/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];zinc/dt [Drug Therapy],"Eda, K.;Mizuochi, T.;Iwama, I.;Inui, A.;Etani, Y.;Araki, M.;Hara, S.;Kumagai, H.;Hagiwara, S. I.;Murayama, K.;Murakami, J.;Shimizu, N.;Kodama, H.;Yasuda, R.;Takaki, Y.;Yamashita, Y.",2018,January,http://dx.doi.org/10.1111/jgh.13812,0,0,5
3371,Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators,"Abnormal handling of copper is the cause of Wilson disease (WD), a rare disorder typified by increased levels in plasma copper not-bound to ceruloplasmin (nCp-Cu, also known as 'free' copper). In Alzheimer's disease (AD), meta-analyses show that copper decreases in brain but increases in serum, due to the nCp Cu component increase. Despite the similarities, a direct comparison of copper biological status in the two diseases has never been carried out. To fill this gap, we evaluated serum copper, ceruloplasmin, nCp-Cu and Cu:Cp in 385 CE and 336 healthy controls previously investigated that were compared with 9 newly diagnosed WD patients. We then assessed 24 h copper urinary excretion in 24 WD patients under D-penicillamine (D-pen) treatment and in 35 healthy controls, and compared results with those of AD patients participating to a D-pen phase II clinical trial previously published. After adjusting for sex and age, serum nCp-Cu and Cu:Cp resulted higher in AD and in WD than in healthy controls (both p < 0.001). While nCp-Cu was similar between AD and WD, Cu:Cp was higher in WD (p < 0.016). 24 h urinary copper excretion in AD patients (12.05 mug/day) was higher than in healthy controls (4.82 mug/day; p < 0.001). 77.8% of the AD patients under D-pen treatment had a 24 h urinary excretion higher than 200 mug/day, suggestive of a failure of copper control. This study provides new insight into the pathophysiology of copper homeostasis in AD, showing a failure of copper control and the Cu:Cp ratio as an eligible marker. Copyright © 2017 Elsevier GmbH",Alzheimer's disease;Ceruloplasmin;Copper;Cu:Cp;Urine;Wilson disease;adult;age distribution;aged;Alzheimer disease/co [Complication];Alzheimer disease/et [Etiology];article;controlled study;copper blood level;copper metabolism;female;human;major clinical study;male;metabolic disorder/et [Etiology];pathophysiology;phase 2 clinical trial (topic);priority journal;sex difference;urinary excretion;urine level;Wilson disease/co [Complication];Wilson disease/dt [Drug Therapy];Wilson disease/et [Etiology];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];unclassified drug;copper dyshomeostasis/et [Etiology];copper not bound to ceruloplasmin/ec [Endogenous Compound],"Squitti, R.;Ghidoni, R.;Simonelli, I.;Ivanova, I. D.;Colabufo, N. A.;Zuin, M.;Benussi, L.;Binetti, G.;Cassetta, E.;Rongioletti, M.;Siotto, M.",2018,January,http://dx.doi.org/10.1016/j.jtemb.2017.11.005,0,0,10
3372,Recent advances in understanding liver fibrosis: Bridging basic science and individualized treatment concepts [version 1; referees: 2 approved],"Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious trigger, tissue damage induces an inflammatory response involving the local vascular system and the immune system and a systemic mobilization of endocrine and neurological mediators, ultimately leading to the activation of matrix-producing cell populations. Genetic disorders, chronic viral infection, alcohol abuse, autoimmune attacks, metabolic disorders, cholestasis, alterations in bile acid composition or concentration, venous obstruction, and parasite infections are well-established factors that predispose one to hepatic fibrosis. In addition, excess fat and other lipotoxic mediators provoking endoplasmic reticulum stress, alteration of mitochondrial function, oxidative stress, and modifications in the microbiota are associated with non-alcoholic fatty liver disease and, subsequently, the initiation and progression of hepatic fibrosis. Multidisciplinary panels of experts have developed practice guidelines, including recommendations of preferred therapeutic approaches to a specific cause of hepatic disease, stage of fibrosis, or occurring co-morbidities associated with ongoing loss of hepatic function. Here, we summarize the factors leading to liver fibrosis and the current concepts in anti-fibrotic therapies. Copyright © 2018 Weiskirchen R et al.",Collagen;Genetic disorders;Hepatitis;Liver fibrosis;Microbiota;nash;Steatosis;Therapy;Viral infection;alcohol abuse;Alstrom syndrome/dt [Drug Therapy];autoimmune disease/dt [Drug Therapy];cell activation;cholestasis;chronic disease;comorbidity;cystic fibrosis/dt [Drug Therapy];disease association;disease predisposition;disorders of mitochondrial functions;dysbiosis/dt [Drug Therapy];endocrine system;endoplasmic reticulum stress;genetic disorder;hepatitis C/dt [Drug Therapy];human;immune system;inborn error of metabolism/dt [Drug Therapy];inflammation;lipotoxicity;liver disease/dt [Drug Therapy];liver fibrosis/co [Complication];liver fibrosis/dt [Drug Therapy];liver fibrosis/et [Etiology];liver fibrosis/pc [Prevention];liver fibrosis/su [Surgery];metabolic disorder/dt [Drug Therapy];microflora;nervous system;nonalcoholic fatty liver;nonhuman;oxidative stress;parasitosis;pathogenesis;practice guideline;primary biliary cirrhosis/dt [Drug Therapy];primary sclerosing cholangitis/dt [Drug Therapy];review;schistosomiasis/dt [Drug Therapy];science;vein occlusion/dt [Drug Therapy];virus infection;Wilson disease/dt [Drug Therapy];alpha tocopherol/dt [Drug Therapy];antifibrotic agent/dt [Drug Therapy];antilipemic agent/dt [Drug Therapy];antivirus agent/dt [Drug Therapy];arginine/dt [Drug Therapy];azathioprine/dt [Drug Therapy];bile acid/ec [Endogenous Compound];budesonide/dt [Drug Therapy];elafibranor/dt [Drug Therapy];fat/ec [Endogenous Compound];fibric acid derivative/dt [Drug Therapy];glucagon like peptide 1 receptor agonist/dt [Drug Therapy];immunosuppressive agent/dt [Drug Therapy];insulin sensitizing agent/dt [Drug Therapy];low molecular weight heparin/dt [Drug Therapy];nicotinic acid/dt [Drug Therapy];nucleoside derivative/dt [Drug Therapy];nucleotide derivative/dt [Drug Therapy];obeticholic acid/dt [Drug Therapy];phenylalanine;pioglitazone/dt [Drug Therapy];praziquantel/dt [Drug Therapy];probiotic agent/dt [Drug Therapy];selonsertib/dt [Drug Therapy];simtuzumab/dt [Drug Therapy];steroid/dt [Drug Therapy];unclassified drug;unindexed drug;ursodeoxycholic acid/dt [Drug Therapy];zinc/dt [Drug Therapy];gr md 02/dt [Drug Therapy],"Weiskirchen, R.;Weiskirchen, S.;Tacke, F.",2018,,http://dx.doi.org/10.12688/f1000research.14841.1,0,0,
3373,Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting,"Background: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. Aim: To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. Methods: We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow up. Results: Thirty-one patients (median age 11 [5-24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child's class A, five to Child's B, and 17 to Child's C. Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363 (35-728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2-20) years. Fifteen of the 17 Child's C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. Conclusions: Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation. Copyright © 2018, Indian Society of Gastroenterology.",Hepatic Wilson's disease;Penicillamine;Symptomatic Wilson's;Wilson's disease;Zinc;acute on chronic liver failure/si [Side Effect];adolescent;adult;article;bacterial peritonitis/si [Side Effect];bleeding/si [Side Effect];chelation therapy;child;clinical article;colon disease/si [Side Effect];death;disease course;disease severity;drug dose reduction;drug efficacy;drug substitution;drug withdrawal;esophagus varices/si [Side Effect];female;fibrosis;follow up;hepatic encephalopathy/si [Side Effect];histology;human;human tissue;hydrothorax;liver biopsy;liver cirrhosis;male;medical record;mental disease;Model For End Stage Liver Disease Score;monotherapy;proteinuria;retrospective study;scoring system;sepsis;septic shock;slit lamp microscopy;Wilson disease/dt [Drug Therapy];young adult;aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/ae [Adverse Drug Reaction];penicillamine/dt [Drug Therapy];zinc sulfate/dt [Drug Therapy],"Gupta, P.;Choksi, M.;Goel, A.;Zachariah, U.;Sajith, K. G.;Ramachandran, J.;Chandy, G.;Kurian, G.;Rebekah, G.;Eapen, C. E.",2018,01 Jan,http://dx.doi.org/10.1007/s12664-018-0829-x,0,1,
3374,Current and promising therapies in autosomal recessive ataxias,"Background & Objective: Ataxia is clinically characterized by unsteady gait and imbalance. Cerebellar disorders may arise from many causes such as metabolic diseases, stroke or genetic mutations. The genetic causes are classified by mode of inheritance and include autosomal dominant, X-linked and autosomal recessive ataxias. Many years have passed since the description of the Friedreich's ataxia, the most common autosomal recessive ataxia, and mutations in many other genes have now been described. The genetic mutations mostly result in the accumulation of toxic metabolites which causes Purkinje neuron lost and eventual cerebellar dysfunction. Unfortunately, the recessive ataxias remain a poorly known group of diseases and most of them are yet untreatable. Conclusion: The aim of this review is to provide a comprehensive clinical profile and to review the currently available therapies. We overview the physiopathology, neurological features and diagnostic approach of the common recessive ataxias. The emphasis is also made on potential drugs currently or soon-to-be in clinical trials. For instance, promising gene therapies raise the possibility of treating differently Friedreich's ataxia, Ataxia-telangiectasia, Wilson's disease and Niemann-Pick disease in the next few years. Copyright © 2018 Bentham Science Publishers.",Ataxia with oculomotor apraxia;Ataxia with vitamin E deficiency;Ataxia-telangiectasia;Autosomal recessive spastic ataxia of charlevoix-saguenay;Cerebrotendinous xantomatosis;Friedreich's ataxia;Niemann-pick disease type C;Recessive ataxia;Refsum's disease;Wilson's disease;alpha tocopherol deficiency;ataxia telangiectasia/dt [Drug Therapy];autosomal recessive disorder/dt [Drug Therapy];Cerebrotendinous Xantomatosis/dt [Drug Therapy];Friedreich ataxia;gene expression;gene mutation;human;metabolite;Niemann Pick disease/dt [Drug Therapy];nuclear magnetic resonance imaging;phase 2 clinical trial (topic);Purkinje cell;randomized controlled trial (topic);Refsum disease;review;Wilson disease/dt [Drug Therapy];chenodeoxycholic acid/dt [Drug Therapy];cholic acid/dt [Drug Therapy];cyclodextrin/dt [Drug Therapy];erythropoietin/ec [Endogenous Compound];fluoxetine/dt [Drug Therapy];frataxin/ec [Endogenous Compound];gamma interferon/ec [Endogenous Compound];miglustat/dt [Drug Therapy];penicillamine/dt [Drug Therapy];taurocholic acid/dt [Drug Therapy];ursodeoxycholic acid/dt [Drug Therapy];zinc derivative/dt [Drug Therapy];autosomal recessive ataxia;oculomotor apraxia,"Picher-Martel, V.;Dupre, N.",2018,,http://dx.doi.org/10.2174/1871527317666180419115029,0,0,
3375,Diagnosis and treatment of wilson disease. [German],"Wilson disease is a rare autosomal recessively inherited copper overload disorder characterized by a highly variable phenotype regarding clinical and biochemical presentation. The diagnostic pathway is often challenging but well characterized by the compounds of the diagnostic ""Leipzig score"". Advances in genotyping are questioning the role of diagnostic liver biopsy. Wilson disease requires life-long medical anti-copper therapy, liver transplantation is in most cases limited to fulminant liver failures. Medical treatment with standard of care drugs shows partly ineffective responses in symptomatic neurologic patients, here the new coppermodulator bischoline-tetrathiomolybdate is a promising new treatment option. Copyright © 2018 Dustri-Verlag Dr. Karl Feistle.",D-penicillamine;Leipzig score;Tetrathiomolybdat;Trientine;Wilson disease;Zinc;autosomal inheritance;genotype;human;liver biopsy;liver transplantation;phenotype;review;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];choline tetrathiomolybdate/dt [Drug Therapy];copper/dt [Drug Therapy],"Weiss, K. H.;Stremmel, W.",2018,May-June,http://dx.doi.org/10.5414/VDX01000,0,0,
3376,Anesthetic management of cesarean delivery for a parturient with Wilson's disease,"Rationale: Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive disorder with a prevalence of 1:50,000 to 1:100,000 live births. Patient concerns: A 26-year-old primipara with WD was admitted to our hospital, due to awaiting delivery. Her main symptoms were slightly higher total bile acid (TBA) and bilateral depressed edema of lower limbs. Diagnosis: She was at 38 weeks and 4 days of gestation with a 15-year history of WD, controlled with penicillamine in the past and replaced by zinc preparations from three months before pregnancy. Outcomes: General anesthesia was successfully administered for a female with WD undergoing cesarean delivery. Lesson: General anesthesia can be administered in an asymptomatic primigravida with WD. Appropriate anesthetics choice can effectively minimize the rates of complications and sequelae. Copyright © 2018 the Author(s).",anesthetic management;cesarean delivery;Wilson's disease;adult;article;blood gas analysis;case report;ceruloplasmin blood level;cesarean section;clinical article;continuous infusion;endotracheal intubation;female;general anesthesia;human;lung clearance;obstetric anesthesia;peripheral edema;primigravida;primipara;priority journal;resuscitation;splenomegaly;Wilson disease/dt [Drug Therapy];atracurium besilate/va [Intravaginal Drug Administration];bile acid/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];midazolam/va [Intravaginal Drug Administration];penicillamine/dt [Drug Therapy];propofol/va [Intravaginal Drug Administration];remifentanil/va [Intravaginal Drug Administration];sufentanil/va [Intravaginal Drug Administration];suxamethonium/va [Intravaginal Drug Administration];tramadol/va [Intravaginal Drug Administration];zinc/dt [Drug Therapy],"Wan, Y.;Jiang, X.;Lin, X.",2018,01 May,http://dx.doi.org/10.1097/MD.0000000000010454,0,0,
3377,A case of refractory elastosis perforans serpiginosa successfully treated with ALAPDT,"Background: A 56-year-old woman with a history of cystinuria on penicillamine therapy for forty years developed numerous erythematous polycyclic and annular plaques with atrophic centers and serpiginous, raised borders on the anterior neck and axilla. A punch biopsy revealed transepidermal elimination of abnormal thick elastic fibers with perpendicular buds. Movat stain outlined coarse tortuous elastic fibers throughout the dermis in a ""bramble bush"" configuration. She was diagnosed with penicillamine-induced elastosis perforans serpignosa (EPS). EPS is a rare condition often seen in the setting of underlying conditions, such as Down's syndrome or Ehlers-Danlos, but also following penicillamine therapy. Penicillamine, a heavy metal chelator, is used to treat various diseases including cystinuria, Wilson's disease, and systemic sclerosis. Long-term administration has been associated with cutaneous adverse events in 20-50% of patients. Penicillamine-induced dermatoses include EPS, cutis laxa, or pseudo-pseudoxanthoma elasticum. Treatment of EPS is difficult and consists of intralesional corticosteroids, retinoids, destruction, and isolated cases of photodynamic therapy (PDT). The patient failed numerous intralesional corticosteroids injections and topical retinoids. She developed significant neck strictures and wrinkling causing physical discomfort and social anxiety. Study: The patient was treated with aminolevulinic acid PDT (ALA-PDT) once weekly for 4 treatments. 1.5 ml of 20% ALA was applied to the neck and occluded with plastic wrap for two hours. The patient was then irradiated with a narrow band LED at 630nm 15 cm away from her neck. The first treatment exposure dose was 99 J/cm2 and the remaining three treatments doses were 130 J/cm2. Pain was assessed during and post-procedure on a numerical scale. Clinical images were taken before and after each treatment session. Results: Clinical images revealed a significant improvement in disease activity and patient satisfaction Conclusion: ALA-PDT is a viable option in treatment-resistant EPS.",adult;adverse drug reaction;anxiety;axilla;case report;clinical article;cutis laxa;cystinuria;dermis;destruction;diagnosis;Down syndrome;drug resistance;drug therapy;Ehlers Danlos syndrome;elastic fiber;elastosis;female;human;injection;middle aged;neck;pain;patient satisfaction;photodynamic therapy;pseudoxanthoma elasticum;punch biopsy;side effect;stain;stenosis;systemic sclerosis;topical drug administration;treatment failure;Wilson disease;wrinkle;aminolevulinic acid;corticosteroid;heavy metal;penicillamine;retinoid;unclassified drug;conference abstract,"Condon, S.;Lucas, J.",2017,March,http://dx.doi.org/10.1002/lsm.22650,0,0,
3378,"Clinical features, laboratory findings and prognosis in fulminant Wilson's disease","Introduction: We evaluated 16 years of experience of pediatric patients with fulminant Wilson's disease (WD). Materials and Methods: Of 98 pediatric patients with fulminant liver failure, we reviewed the clinical and laboratory data of 12 (12.2%) who had fulminant WD. Results: There were a total of 12 fulminant WD patients. Mean age at time of arrival was 9.3}1.59 years (range: 7.3-12.5 y). 4 patients did not have findings of encephalopathy, while 2 patients had stage 1, 3 had stage 2 and 3 had stage 3 encephalopathy at the time of admission. Mean hemoglobin, white blood cell count and thrombocyte levels were 7.43}2.67 g/dL, 20,330}12,430/mm3 and 131,820}93,650/mm3, respectively. The liver function tests at the time of reference were; total bilirubin: 39.26}15.66 mg/dL, direct bilirubin: 27}11.76 mg/dL, AST: 513.66}943.6 U/L, ALP: 234}250.6 U/L, INR 4}2.25. 9 patients had low seruloplasmin levels. Mean PELD values, Child Pugh scores and new Wilson indexes were 32.1}11.5 (range: 16-48), 11.44}1.66 (range: 10-15) and 15.44}1.94 (range: 12-18), respectively. Plasmapheresis was used in all patients, while D-penicillamine were also given in 3 patients, D-penicillamine, zinc and steroids to 2; trientine, zinc and steroids to 2 patients. 4 patients died, 6 underwent liver transplantation and 2 spontaneously survived. Histopathologic examinations of explant livers or postmortem liver necropsy samples were evaluated in 9 patients. 7 patients had cirrhosis, 1 had chronic active hepatitis and 1 had diffuse microvesicular steatosis. Mean tissue copper level was 440}347 mugr/g dry liver tissue. Conclusion: Fulminant WD is extremely fatal if liver transplant cannot be performed. Introduction of plasmapheresis and chelating therapy may be life-saving in low risk patients. Most patients have findings of cirrhosis on liver histopathological examination at time of arrival.",aspartate aminotransferase level;autopsy;chelation;child;Child Pugh score;chronic active hepatitis;clinical evaluation;clinical feature;explant;fatty liver;female;fulminant hepatic failure;histopathology;human;human cell;human tissue;international normalized ratio;leukocyte count;liver cirrhosis;liver function test;liver graft;liver transplantation;low risk patient;major clinical study;male;plasmapheresis;prognosis;risk assessment;thrombocyte;Wilson disease;bilirubin glucuronide;endogenous compound;hemoglobin;penicillamine;steroid;trientine;zinc;conference abstract,"Baris, Z.;Ozcay, F.;Balci Sezer, O.;Haberal, M.",2018,May,,0,0,
3379,"Three patients with glycosylation deficiencies, chronically elevated transaminases, and low serum ceruloplasmin and copper, caused by mutations in the gene encoding the transmembrane protein TMEM199","Background: A decade ago we reported on four children with glycosylation deficiencies and a liver disease mimicking Wilsondisease, but without known genetic cause. Two (patients #1 and #2) were later diagnosed with phosphoglucomutase-1 deficiency. Aims: Here we present a long-term follow-up on the other two children (#3 and #4), and present data on a third, unrelated child (#5), all diagnosed with TMEM199-deficiency. Patients: Patients #3 and #4 are Italian healthy young adults investigated for hypertransaminasemia when they were 2 y.o. They also had increased values of total and LDL cholesterol, creatinine kinase, and alkaline phosphatase. Ceruloplasmin and serum copper were low in spite of a normal urinary basal and after penicillamine excretion. Liver biopsy confirmed ultrasonographic mild fibrosis/ steatosis, with mildly increased copper content; Wilson-disease and aceruloplasminemia were ruled out by appropriate tests. Transferrin glycosylation was consistent with a CDG-II. Patient #5 (Italian, now2 y.o.) presented a similar picture already at age 1 year; he did not undergo liver biopsy. Results: Exome-sequencing identified in all compound heterozygous mutations in TMEM199 (frameshift with a premature stop, and a missense change, respectively). Western Blot analysis showed absence of the TMEM199 protein in patient fibroblasts. Conclusions: Our patients present a recently described Wilson-disease mimicking rare disease with chronically elevated transaminases, low serum ceruloplasmin and copper, caused by mutations in gene encoding transmembrane protein TMEM199. The mechanisms potentially involve at least partial loss of either or both of the copper transporting proteins ATP7A and ATP7B.",adult;case report;ceruloplasmin blood level;child;clinical article;congenital disorder of glycosylation type 2;copper blood level;diagnosis;excretion;fibroblast;fibrosis;follow up;frameshift mutation;genetic susceptibility;heterozygosity;human;human tissue;hypertransaminasemia;liver biopsy;male;missense mutation;rare disease;steatosis;Western blotting;whole exome sequencing;Wilson disease;young adult;alkaline phosphatase;ceruloplasmin;creatine kinase;endogenous compound;low density lipoprotein cholesterol;membrane protein;Menkes protein;penicillamine;phosphoglucomutase;transferrin;Wilson disease protein;conference abstract,"Poeta, M.;Zielinska, K.;Maccarana, M.;Mandato, C.;Ng, B. G.;Di Nuzzi, A.;D'Acunto, E.;Pierri, L.;Ecklund, E.;Freeze, H.;Vajro, P.",2017,October,http://dx.doi.org/10.1016/j.dld.2017.09.021,0,0,
3380,Addressing Generic-Drug Market Failures - The Case for Establishing a Nonprofit Manufacturer,,capital;competition;drug approval;drug cost;drug industry;drug marketing;food and drug administration;health care access;human;investment;pharmacy;priority journal;profit;review;toxoplasmosis/dt [Drug Therapy];Wilson disease/dt [Drug Therapy];biosimilar agent;generic drug;pyrimethamine/dt [Drug Therapy];trientine/dt [Drug Therapy],"Liljenquist, D.;Bai, G.;Anderson, G. F.",2018,17 May,http://dx.doi.org/10.1056/NEJMp1800861,0,0,
3381,Causes of metallic taste in the mouth,"Learning Objective #1: Evaluate a patient who reports having a metallic taste in the mouth Learning Objective #2: Review differential for elevated copper level in an adult CASE: Patient is a 45 year old female with PMH of lumbar radiculopathy and Tourette's who presented to the physician's office complaining of 3 weeks of metallic taste in the mouth. She works as a flight attendant but denied recent international travel. She denied any new medications. Her medications included naproxen, oral contraceptive, and Botox injections for Tourette's. Patient denied possibility of pregnancy. Patient was already seen by a dentist, urgent care physician, and ENT for evaluation. Since the symptoms were thought to be attributed to a sinus infection, she had completed a course of azithromycin. Symptoms improved after the first two tablets but then returned. At the urgent care center, the metallic taste was thought to be related to allergies, for which she had taken loratadine without relief. The ENT advised the patient to suck on lemon drops, but these also failed to help. Patient reported consuming pine nuts, which she thought may be a contributing factor. The clinical pharmacist was consulted to explore possible medication-induced causes of metallic taste. Previous literature included a case report of a patient who experienced metallic taste following initial botulinum toxin A injections, but symptoms lessened after subsequent injections. This was thought to be from their effects on zinc metabolism. After checking routine labs and heavy metals (i.e. lead, copper and mercury), our patient was found to have an elevated copper of 197 ug/dL, compared to a normal level of 72-166 ug/dL. Repeat level was similar. BMP, CBC, and TSH were normal. Wilson's disease was ruled out. It was found that the copper elevation may be contributed to the oral contraceptive, which the patient didn't wish to stop. The physician also consulted with poison control and occupational medicine to rule out occupational exposure. Recommendation was made against treating the elevated copper level. IMPACT: This case added to the literature involving metallic taste induced by medications and highlights the value of a pharmacist in performing a medication review to evaluate possible causes. DISCUSSION: The majority of disturbances in taste are the result of loss of smell, which may be contributed commonly to allergic rhinitis, chronic rhinosinusitis or an upper respiratory infection. Therefore, examination of the nose, mouth and cranial nerves are key. Metallic taste can also be attributed to external exposure, pregnancy (which should be ruled out when appropriate) or medications that affect metabolism of metals such as zinc or copper, of which levels should also be evaluated. In our case, the botulinum injections and oral contraceptive were considered as possibilities for causing the patient's symptoms. A third possibility was pine nut syndrome, as the symptoms correlated with the patient's reported consumption of pine nuts.",adult;allergic rhinitis;allergy;anosmia;case report;chronic rhinosinusitis;clinical article;clinical evaluation;cranial nerve;dentist;female;human;injection;learning;lemon;lumbar region;metallic taste;middle aged;mouth;nonhuman;nose;nut;occupational exposure;occupational medicine;pharmacist;physician;pregnancy;radiculopathy;tablet;thinking;travel;upper respiratory tract infection;Wilson disease;world health organization;zinc metabolism;azithromycin;botulinum toxin A;endogenous compound;loratadine;mercury;naproxen;oral contraceptive agent;poison;thyrotropin;zinc;conference abstract,"Lu, C.;Lee, J.;Marrast, L. M.",2018,,,0,0,
3382,Unusual presentation of wilson disease in a pediatric patient: Case report,"Objective: Review a case of an unusual primary neuropsychiatric presentation of Wilson disease in a pediatric patient. Background: Wilson disease is a genetic disorder of copper metabolism that affects both children and adults and typically presents with neuropsychiatric and/or hepatic symptoms due to copper deposition. Diagnosis is made with a combination of clinical findings including presence of Keyser-Flescher (KF) rings and biochemical testing and confirmed with testing of the ATP7B gene. Neurologic manifestations include choreoathetosis, dystonia, dysmetria, ataxia, and dysarthria. Psychiatric manifestations include mood disorders, behavioral changes including compulsions or disinhibition. KF rings are present in an estimated 90% of patients with neuropsychiatric manifestations. Pediatric patients typically present with hepatic symptoms, and rarely present with neuropsychiatric symptoms alone. Treatment is chelation of copper (Weiss, GeneReviews, 2016). Design/Methods: NA Results: We present a case of a 10 year old girl, with subacute onset of dysarthria and ataxia with falls. Examination was notable for flat affect, disinhibition, and findings localizing to the cerebellum with choppy smooth pursuits on extra-ocular movements without nystagmus, motor impersistence, dysmetria, ataxia, widebased shuffling gait, positive Romberg, and inability to perform stress gaits. There was no choreoathetosis or dystonia though the patient had dysarthria with odd slow, halting speech. Lab work revealed elevated transaminases. Neuroimaging was unremarkable, and ophthalmologic exam did not reveal KF rings. Ceruloplasmin and serum and urinary copper screening were concerning for Wilson disease. Diagnosis was confirmed on ATP7B sequencing for the presence of two pathologic variants, c.3955C>T. Liver biopsy demonstrated elevated copper content. Treatment with oral zinc was initiated, and she had rapid improvement of neurologic symptoms, became ambulatory within a few weeks, with an almost complete return to baseline within a few months. Conclusions: This case presentation demonstrates a unique presentation of Wilson disease in a child with predominantly neuropsychiatric symptoms that responded to therapy.",adult;behavior change;blunted affect;case report;cerebellum;chelation;child;choreoathetosis;clinical article;compulsion;copper metabolism;diagnosis;dysarthria;dysmetria;dystonia;female;gene frequency;girl;human;human tissue;hypertransaminasemia;liver biopsy;neuroimaging;optokinetic nystagmus;school child;shuffling gait;smooth pursuit eye movement;stress;Wilson disease;ceruloplasmin;endogenous compound;Wilson disease protein;zinc;conference abstract,"DiSano, M.;Friedman, N.;Parikh, S.",2018,,,0,0,
3383,Wilson disease. [German],"Wilson disease is a rare hereditary disorder of copper metabolism. The genetic defect is caused by various mutations in the copper-transporting enzyme ATP7B, located mainly in the liver and brain. Clinical symptoms are highly variable, with any combination of hepatic and/or neurological or psychiatric manifestations. The age of onset varies from early childhood to young adults and can even be manifested in later ages. The clinical diagnosis is based on a combination of clinical, biochemical and molecular markers. Treatment using chelating agents and zinc salts is effective when started early or even better at presymptomatic stages of the disease. Copyright © 2018, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.",Central nervous system;Chelating agents;Copper toxicity;Liver;Wilson disease protein;article;clinical feature;copper metabolism;gene mutation;human;onset age;Wilson disease;chelating agent;zinc derivative,"Huster, D.",2018,01 May,http://dx.doi.org/10.1007/s11377-018-0260-y,0,0,1329
3384,Indian childhood cirrhosis - Down but not out: Report of a rare case with a practical clinicopathological diagnostic approach,"Indian childhood cirrhosis is an entity believed to be on the verge of extinction. We present the case of a 13-month-old girl presenting acutely with jaundice, fever, and persistently increasing bilirubin. Investigations revealed direct hyperbilirubinemia, elevated transaminases, anemia, a blood with few schistocytes, positive direct coombs test, and deranged prothrombin time. Viral, autoimmune, and metabolic workup was unremarkable. Ultrasonography showed chronic liver disease, portal hypertension, and ascites. Due to numerous confounding factors and a low index of suspicion, the diagnosis of Indian childhood cirrhosis remained elusive and was clinched only on liver biopsy, albeit more than three weeks later, shortly after which the child expired. The timing and technique of the liver biopsy may have profound impact on the ultimate clinical outcome. Close coordination between the clinical and pathological teams is essential for deciphering acute presentations where the etiology is uncertain. We highlight the clinical considerations, varied morphological pointers, and offer a diagnostic algorithm facilitating the consideration of this disease. Copyright © 2018 Journal of Postgraduate Medicine.",Biopsy;copper;rhodanine;Wilson disease;abdominal distension;aminoacidemia;anasarca/su [Surgery];anemia;antibiotic therapy;ascites/dt [Drug Therapy];autoimmune hemolytic anemia/di [Diagnosis];autoimmune hepatitis/di [Diagnosis];bacterial growth;bacterial peritonitis/di [Diagnosis];bacterial peritonitis/dt [Drug Therapy];case report;ceruloplasmin blood level;child;chronic liver disease/di [Diagnosis];clinical article;clinical feature;Coombs test;copper blood level;diagnostic test;differential diagnosis;drug treatment failure;echography;esophagus varices;feces color;female;ferritin blood level;fever;foot edema;gastrointestinal endoscopy;hemoglobin blood level;hemolytic anemia;hepatomegaly;hepatosplenomegaly;human;hyperbilirubinemia;Indian childhood cirrhosis/di [Diagnosis];irritability;jaundice;kidney tubule disorder;leukocyte count;liver biopsy;liver failure;liver fibrosis;mineral supplementation;needle biopsy;neutrophilia;osmotic fragility;portal hypertension/di [Diagnosis];preschool child;prothrombin time;reticulocyte count;review;Staphylococcus infection/di [Diagnosis];Staphylococcus infection/dt [Drug Therapy];steatosis;steroid therapy;tachycardia;vitamin supplementation;albumin/va [Intravaginal Drug Administration];alpha tocopherol;amikacin/dt [Drug Therapy];ascorbic acid;calcium;cefotaxime/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];furosemide/va [Intravaginal Drug Administration];glucose;haptoglobin/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];hemosiderin/ec [Endogenous Compound];mineral;potassium chloride;prednisolone/dt [Drug Therapy];prednisolone/vi [Intravitreal Drug Administration];retinol;sodium chloride;spironolactone/vi [Intravitreal Drug Administration];tazobactam/dt [Drug Therapy];tazobactam/va [Intravaginal Drug Administration];vitamin B group;vitamin D;vitamin K group;zinc,"Gaur, K.;Sakhuja, P.;Mandal, R. N.;Kapoor, S.",2018,April-June,http://dx.doi.org/10.4103/jpgm.JPGM-359-17,0,0,
3385,Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson's disease: A case report,"Background: Wilson's disease (WD) is an autosomal recessive disorder characterized by copper accumulation. ATP7B gene mutations lead to ATP7B protein dysfunction, which in turn causes Wilson's disease. Case presentation: We describe a male case of Wilson's disease diagnosed at 10 years after routine biochemical test that showed low serum ceruloplasmin levels and Kayser-Fleischer rings in both corneas. Analysis of the ATP7B gene revealed compound heterozygous mutations in the proband, including the reported c.3517G>A mutation and a novel c.532_574del mutation. The c.532_574del mutation covered a 43-bp region in exon 2, and resulted in a frameshift mutation (p.Leu178PhefsX10). By base sequence analysis, two microhomologies (TCTCA) were observed on both deletion breakpoints in the ATP7B gene. Meanwhile, the presence of some sequence motifs associated with DNA breakage near the deletion region promoted DNA strand break. Conclusions: By comparison, a replication-based mechanism named fork stalling and template switching/ microhomology-mediated break-induced replication (FoSTeS/MMBIR) was used to explain the formation of this novel deletion mutation. Copyright © 2018 The Author(s).",atp7b;FoSTeS/MMBIR;Novel mutation;Wilson's disease;article;case report;ceruloplasmin blood level;child;Chinese;clinical article;copper blood level;DNA sequence;DNA strand breakage;gene deletion;gene mutation;headache;human;male;missense mutation;motor dysfunction;nuclear magnetic resonance imaging;Sanger sequencing;school child;slit lamp microscopy;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];Atp7b gene,"Liu, G.;Ma, D.;Cheng, J.;Zhang, J.;Luo, C.;Sun, Y.;Hu, P.;Wang, Y.;Jiang, T.;Xu, Z.",2018,12 Apr,http://dx.doi.org/10.1186/s12881-018-0567-z,0,0,
3386,Clinical presentation and outcome of Wilson's disease patients in a monocentric cohort of liver reference center,"Background and Aims: Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism, leading to liver cirrhosis and neurologic disorders. Clinical data on larger cohorts are limited, owing to low disease frequency. The aim is to determine clinical presentation and outcome of patients with WD in a cohort of patients from a French liver reference center. Method: This is a retrospective analysis of patients with diagnosis of WD in a liver reference center (Paul-Brousse Hospital, Villejuif, France). Patients were evaluated clinically, biologically, morphologically and genetically. Hepatic involvement was assessed with liver biopsy and/or liver stiffness measurement. Results:We included 107 patients with hepatic symptoms of the WD, 54 (50.5%) females and 53 (49.5%) males, from 1974 to 2016. The mean follow up was 15 years [extr: 1-44 years]. Fifty-seven (53.3%) had neurological symptoms (mixed symptoms, neurologic and hepatic) at admission. The mean age at diagnosis was 20.1 ( +/- 10.54) years with a difference between the age concerning the patients with hepatic symptoms (17 +/- 8.6 years) and mixed symptoms (23 +/- 11.4 years) (p = 0.0081). 65 patients (70%) had liver pathological analysis and 72 (67%) had liver stiffness measurement. Seventy-three patients (68%) had cirrhosis at diagnosis of the disease. Forty-three patients (77%) had cirrhosis among patients with mixed symptoms and 30 (61%) in patients with isolated hepatic symptoms. Thirty-four patients (32%) were transplanted, at a mean age of 27 ( +/- 12.2) years. Among patients who required liver transplantation 18 (52%) had decompensated cirrhosis, 8 (23%) fulminant liver failure, 8 (23.5%) severe neurological disease and 5 (14%) liver cancer. The chelating treatment was very predominantly D Penicillamine, in 104 (97%) patients. A change in treatment was necessary in 37 (35%) patients because of adverse events to Trientine or Zinc salts. Four patients died in this cohort; two after primary liver cancer (1 HCC and 1 cholangiocarcinoma), one after hemorrhagic stroke and one after liver transplantation for severe neurological symptoms. Conclusion: At presentation of WD, two thirds of patients referred to a reference center of hepatology, had cirrhosis and one-third required liver transplantation. Cirrhosis was diagnosed in 77% patients who have neurological symptoms of the disease. Even if WD can be a severe disease, the prognosis is good for patients in charge in a specialized center.",adolescent;adult;adverse drug reaction;bile duct carcinoma;brain hemorrhage;cancer prognosis;chelation;clinical assessment;cohort analysis;decompensated liver cirrhosis;diagnosis;female;follow up;France;fulminant hepatic failure;human;liver biopsy;liver cancer;liver stiffness;liver transplantation;major clinical study;male;neurologic disease;prognosis;retrospective study;side effect;Wilson disease;young adult;endogenous compound;penicillamine;trientine;zinc derivative;conference abstract,"Sobesky, R.;Darce, M.;Agostini, H.;Fernandez, I.;Usardi, A.;Adam, R.;Cherqui, D.;Gonzales, E.;Jacquemin, E.;Samuel, D.;Poujois, A.;Woimant, F.;Duclos-Vallee, J. C.",2018,April,,0,0,
3387,Phenotypic characteristics and improvement of liver stiffness measurement during follow-up in patients with Wilson's disease,"Background and Aims: Wilson's disease (WD) is an autosomal recessive genetic disorder leading to hepatic and neurologic impairement. The aim of our study was to assess phenotypic and therapeutic particularities of WD patients treated in a tertiary hospital between 2012-2016. Method: A retrospective study has been conducted including 88 patients diagnosed with WD during the defined period. Results: Age at diagnosis below 7 years was found in 12.9% of cases, between 7-18 years in 44.7%, 18-35years in 37.6% and >35years in 7%. At time of diagnosis, hepatic disease was encountered in 67%, hepatic and neurologic disease in 27.3%, exclusive neurologic disease in 5.7%. In patients with hepatic WD, 30.3% had compensated and 14.2% decompensated liver cirrhosis (LC), 50% chronic hepatitis, and 5.3% acute liver failure. In patients with hepatic and neurologic impairment, 66.6% had compensated and 11% decompensated LC and 22.2% chronic hepatitis. Exclusive hepatic disease was encountered in 77.7% of children in comparison to only 50% of adults (p = 0.02). At last follow-up visit, treatment consisted in D-penicillamine 32.1%, trientine 8.3%, zinc 5.9%, Dpenicillamine and zinc 41.7%, trientine and zinc 3.6%, liver transplantation being performed in 8.4% of cases. In patients with hepatic disease, clinical improvement was established in 65.8% of patients while worsening of disease in only 20.3%. In patients with hepatic and neurologic disease, clinical improvement was found in 59.1%, while worsening in 22.7%. Patients with isolated neurological impairment had a favorable clinical course in 75% of cases and the rest worsened. Liver stiffness measured in all patients with compensated liver diseases at the moment of diagnosis decreased significantly after 12 months of chelating therapy (14.6 +/- 10.9 vs 8.4 +/- 5.1 kPa, p < 0.0001). Conclusion: In a romanian tertiary center, WD with hepatic phenotype is the most frequently encountered especially in children and exclusive neurological disease is rare. A favorable disease course could be confirmed in >60% of cases in all phenotypes, with significant decrease of liver stiffness. During the study period, liver transplantation was performed in <9% of cases due to timely diagnosis and effective chelating therapy.",acute liver failure;adult;chelation;child;chronic hepatitis;decompensated liver cirrhosis;diagnosis;female;follow up;human;liver stiffness;liver transplantation;major clinical study;male;phenotype;rest;retrospective study;tertiary care center;Wilson disease;endogenous compound;penicillamine;trientine;zinc;conference abstract,"Iacob, R.;Iacob, S.;Oana, A.;Cristina, A. D.;Constantinescu, A.;Lupescu, I. G.;Popescu, I.;Gheorghe, L.",2018,April,,0,0,
3388,Long term outcomes of treatment with Trientine in Wilson disease: Final results from a multicentre study in patients withdrawn from d-Penicillamine therapy,"Background and Aims: Trientine dihydrochloride (Trientine; UNIVAR B.V.) is a common treatment for Wilson Disease. This study aimed to assess efficacy, safety, and tolerability outcomes of Trientine chelator-based treatment after withdrawal of d-Penicillamine. ClinicalTrials.gov Identifier: NCT02426905. Method: In a multicenter, retrospective cohort study assessments were performed for 6,12, 24, 36 and 48 month time points and at the latest available follow-up after Trientine initiation. A total of 81 patients were enrolled into the study, with 77 (95.1%) patients included in the intention to treat (ITT) population. Primary endpoint was investigator rated outcome of hepatic and neurologic symptoms, additional efficacy analysis included copper parameter, LFTs. Safety reporting included SAE and discontinuation rate. Results: Of the 77 patients included in the ITT population, 16 (20.8%) patients were under the age of 18 years. Reasons for discontinuation of D-Penicilamine were adverse events (58 [75.3%] patients) or lack of clinical improvement (12 [15.6%] patients). On average, patients were treated with trientine for 73.3 (+/-74.76) months. The mean total dose per day during treatment was 1005.7 (+/-425.32) mg. Treatment with trientine improved hepatic symptoms in 49.4% of patients, with 35.1% asymptomatic, 10.4% unchanged and 5.2% worsened, whereas neurological symptoms remained unchanged in 36.4% of patients, with 46.8% asymptomatic, 14.3% improved and 2.6% worsened. Overall, the median NCC concentration showed a decrease from baseline to latest follow up (n = 35 [-0.613 +/- 1.7318]). A total of 17 (22.1%) patients experienced a serious TEAE. The majority of these TEAEs were resolved, resolved with sequelae or improved. Only two serious TEAEs were considered related to trientine and both resolved. Treatment with trientine was permanently discontinued due to a TEAE in 1 (1.3%) patient (anemia). Two (2.6%) patients discontinued trientine treatment due to inadequate hepatic response. Conclusion: Anti-copper therapy with trientine was effective following withdrawal of treatment with d-Penicillamine. Trientine well tolerated and the rates of symptomatic deterioration were lower than reported in previous series. These findings supports Trientine's prominent role in Wilson Disease management.",adult;adverse event;anemia;cohort analysis;comparative effectiveness;complication;deterioration;drug efficacy;drug withdrawal;female;follow up;human;major clinical study;male;multicenter study;pharmacokinetics;retrospective study;Wilson disease;young adult;penicillamine;trientine;conference abstract,"Weiss, K. H.;Manolaki, N.;Zuin, M. G.;Kruse, C.;Dhawan, A.",2018,April,,0,0,
3389,Long-term efficacy and safety of WTX101 in Wilson disease: Data from an ongoing extension of a phase 2 study (WTX101-201),"Background and Aims: WTX101 (bis-choline tetrathiomolybdate) is a copper-protein-binding agent that reduces plasma non-ceruloplasmin bound copper (NCC) by forming tripartite complexes with albumin and increases biliary copper excretion. In a Phase 2 study in Wilson disease (WD), oral once-daily WTX101 rapidly reduced NCCcorrected (corrected for copper in tripartite complexes), improved disability and neurological status, and stabilized liver function over 24 weeks. We present preliminary 72-week efficacy and safety data from an ongoing Phase 2 study extension, the first prospective report on long-term disease control with WTX101 in WD. Method: All 22 patients completing the 24-week open-label, singlearm Phase 2 study opted to continue once-daily response-guided treatment with WTX101 in the extension. Key parameters reviewed to 72 weeks included hepatic status, NCCcorrected, neurological status, safety and tolerability. Results: Mean ALT, international normalized ratio, albumin, and Model for End-Stage Liver Disease score improved or remained stable between week 24 and 72. Reversible ALT elevations requiring dose adjustments, observed in 39% of patients (at > = 30 mg/day) to week 24, were not observed in the extension. Elevated mean (SD) NCCcorrected at baseline (3.6 [2.1] muM) was reduced and controlled at week 24 (0.9 [1.0] muM) and remained controlled at week 72 (0.5 [0.7] muM) with accompanying continuous improvements in disability and neurological status in most patients. Low platelet (56%) and neutrophil (32%) counts were common at baseline, with similar reporting throughout follow-up; low hemoglobin was infrequent. Most cytopenias were not accompanied by low NCC levels and unlikely to reflect copper deficiency. Two subjects had evidence of neutropenia accompanied by mild anemia and low NCC potentially consistent with copper deficiency at week 36 and 72, respectively; both responded rapidly to dose reduction. Overall, the number of reported adverse events (AEs) and serious AEs (SAEs) decreased by more than 50% fromweeks 1-24 (175 AEs and 11 SAEs) toweeks 25- 72 (71 AEs and 4 SAEs). Between week 24 and 72, 89% of AEs were mild or moderate, with 89% considered unrelated or unlikely related to therapy. Conclusion: Once-daily treatment of WD patients with WTX101 up to 72 weeks provided long-term disease control as shown by sustained improvements in NCC, disability and neurological status and stable hepatic function, with a favorable tolerability profile.",adult;adverse event;anemia;clinical article;controlled study;copper deficiency;cytopenia;disability;disease control;drug efficacy;female;follow up;human;human cell;human tissue;international normalized ratio;liver function;male;Model For End Stage Liver Disease Score;neutropenia;neutrophil;phase 2 clinical trial;thrombocyte;Wilson disease;albumin;endogenous compound;hemoglobin;conference abstract,"Weiss, K. H.;Askari, F.;Ferenci, P.;Ala, A.;Czlonkowska, A.;Nicholl, D.;Bronstein, J.;Bega, D.;Schilsky, M.",2018,April,,0,0,
3390,Case report: Pancytopenia and hepatosplenomegaly in a 31-year old male,"Wilson's disease is an autosomal recessive inherited disease, resulting in copper deposition in all organs and affecting primarily the liver and the brain. Clinical presentation of patients can be ambiguous and initial misdiagnosis is not unusual. This case report describes a 31-year old male patient who was transferred to our haemato-oncological department with pancytopenia and suspected malignant liver disease. Further anamnesis revealed a history of progressive muscle weakness, ataxia and gait disturbance over the past 4 years. These findings had been interpreted before as dissociative movement disorder and adaptive disorder and psychiatric medication had been started. Consecutive diagnostic investigations showed no evidence of an underlying hematologic disease, despite of a proven pancytopenia and hepatosplenomegaly. Elevated liver enzymes and the history of progressive neuropsychiatric symptoms raised our awareness for further diagnostic beyond hematologic malignancies. Finally an ophthalmological slit-lamp exploration revealed a Kayser-Fleischer ring which led to the suspected diagnosis of Wilson's disease, which was later confirmed by liver biopsy. Chelating therapy with D-penicillamine was started and over the next months the majority of his symptoms resolved.",adult;anamnesis;ataxic gait;awareness;case report;chelation;clinical article;diagnosis;dissociation;hematologic malignancy;hepatosplenomegaly;human;hypertransaminasemia;liver biopsy;male;mental disease;muscle weakness;pancytopenia;slit lamp;Wilson disease;penicillamine;conference abstract,"Hockl, P.;Dax, K.;Hayat-Khayyati, A.;Greul, R.",2018,March,http://dx.doi.org/10.1007/s12254-018-0401-5,0,0,
3391,Psychological signs as the only presentation of Wilson's disease in an 11-year-old boy,"Wilson's disease (WD) is a rare autosomal recessive disease due to copper metabolism disturbance. The clinical presentation spectrum of Wilson's disease is wide and initial findings of the disease depend on the organ involved. Neurologic disorders can develop insidiously or precipitously with intention tremor, dysarthria, rigid dystonia, Parkinsonism, deterioration in school performance or behavioral changes. This article is presenting an 11-yr old boy with chief complaint of falling and upper limb spasm. He referred to the Neurology Department, Ghaem Hospital, Mashhad, northeastern Iran in 2016. His symptoms began from 6 months earlier as mood instability (prolonged spontaneous crying). He was also suffering from occasionally tremor and micrographia. Initial investigations were normal and with diagnosis of depression and psychiatric problems, he had undergone treatment with fluoxetine and risperidone. Wilson's disease should be considered in the diagnosis of all children with psychiatric and musculoskeletal symptoms. Copyright © 2018, Iranian Child Neurology Society. All rights reserved.",Childhood;Iran;Psychological symptoms;Wilson disease;abdominal pain;article;athetosis;case report;child;clinical article;depression/dt [Drug Therapy];dose response;drug megadose;falling;human;male;mental instability;muscle spasm;physical examination;school child;spasticity;symptom;tremor;Wilson disease/dt [Drug Therapy];fluoxetine/dt [Drug Therapy];lamotrigine/dt [Drug Therapy];olanzapine/dt [Drug Therapy];risperidone/dt [Drug Therapy];zinc sulfate/do [Drug Dose];zinc sulfate/dt [Drug Therapy],"Beiraghi Toosi, M.;Akhondian, J.;Ashraf Zadeh, F.;Donyadideh, N.;Javid, A.",2018,Spring,http://dx.doi.org/10.22037/ijcn.v12i2.14316,0,0,
3392,Pediatric Wilson disease: A study on clinical profile and treatment outcome from a tertiary care center in North India,"Background: Wilson disease is a rare disorder of copper metabolism. Its protean hepatic presentations include acute hepatitis, acute liver failure, acute on chronic liver failure, portal hypertension, asymptomatic hepatomegaly, raised liver enzymes and gall stones. Extrahepatic manifestations are also well known. There is a paucity of data on this disease and its outcome. We here present one of the largest cohort of pediatric Wilson disease patients managed at our center. Method: Clinical profile & outcome of 107 pediatric Wilson disease cases from year 2006 to 2016 were retrospectively analysed. Diag-nosis was based on KF rings, low serum ceruloplasmin & high 24 hour urine copper as per standard cut offs +/- liver histology. Cases with atleast 12 months follow up post chelation were analysed. Outcome was categorised as (1) Complete improvement: Asymp-tomatic with normal synthetic function (2) Partial improvement: AST/ALT elevation and synthetic dysfunction which are resolving (3) Deterioration: Worsening synthetic function or neurological status & (4) Death. Result: Of the 107 patients with age ranging from 3 years to 18 years managed at our center, presenting symptoms were jaundice in 60 (56.07%), ascites in 49 (45.7%), cola colored urine in 5 (4.6%), encephalopathy in 11 (10.2%), GI bleed in 18 (16.8%) and extra GI bleed (cutaneous, hematuria, epistaxis) in 13 (12.1%).Neurological presentation was seen in in 23 (21.4%) and psychiatric presentation in 5 (4.6%) patients. Consanguinity was present in 15 (14%) whereas family history of Wilson (hepatic/neurological/hepatic with neuro) was seen in 44 (41.1%) patients. Clinical examination showed hepatomegaly in 88 (82.2%), splenomegaly in 69 (64.4%), ascites in 40 (37.3%), signs of cirrhosis (including clubbing, spider angioma, skin changes) in 39 (36.4%) and sunflower cataract in 4 (3.7% patient-s).Gall stones in 2 (1.8%), nephrolithiasis in 3 (2.8%), MPGN and pancreatic involvement in 1 (0.9%) were also seen. Familial Wilson disease was present in 13 (12%).4(3.7%) of the patients' parents (3 male and 1 female) were diagnosed subsequently. Types of presentation was hepatic in 87 (81.3%) or hepatolenticular in 20 (18.7%). The PELD score at admission varied from 0-45.8 (mean 11.36).Child Pugh Score was A in 53 (49.5%), B in 13 (12.1%) and C in 41 (38.3%) patients. KF ring was present in 63 (72.4%) of hepatic Wilson and 18 (90%) of hepatolenticular Wilson patients. Serum Ceruloplamin was low\20 mg/dl) in 81 (93%) of hepatic and 19 (95%) of hepatolenticular wilson.67.2% of them had value\or = 10 mg/dl.Urine copper was performed in 90 patients with 66 (73.3%) having value[100 lg/24 hours and 11 (12.2%) with value [40 lg/24 hours. Liver biopsy was done in 53 (49.5%) cases contributing to diagnosis. Types of hepatic presentation in were cirrhosis in 45 (46.3%), chronic liver disease in 7 (7.2%), ACLF in 13 (13.4% & 53.8% due to Wilson flare up, ALF in 2 (2.06%), acute hepatitis in 18 (18.5%) and asymptomatic in 13 (13.4%). Patients were started on chelation therapy with combined D Penicillamine and Zinc and was followed up after 1 year.64 (59.8%) had complete resolution, 26(24.2%) had partial improvement, 9 (14%) had deterioration of which 2 patients underwent liver transplant, 4 (3.7%) were lost to follow up & 4 (3.7%) died. Conclusion: Wilson disease is a common metabolic liver disease in children and it responds well to chelation therapy. Patients who present with ALF/ACLF and those with end stage liver disease may require liver transplantation.",acute hepatitis;acute on chronic liver failure;adolescent;adult;ascites;aspartate aminotransferase level;cataract;ceruloplasmin blood level;chelation therapy;Child Pugh score;clinical assessment;clinical examination;cohort analysis;consanguinity;death;deterioration;diagnosis;end stage liver disease;epistaxis;family history;female;follow up;gallstone;gastrointestinal hemorrhage;hematuria;hepatomegaly;human;human tissue;India;jaundice;liver biopsy;liver cirrhosis;liver graft;liver histology;low drug dose;major clinical study;male;membranoproliferative glomerulonephritis;nephrolithiasis;nonhuman;pancreas;remission;retrospective study;skin;spider vein;splenomegaly;sunflower;tertiary care center;urine;Wilson disease;endogenous compound;penicillamine;zinc;conference abstract,"Menon, J.;Thapa, B. R.;Lal, S.;Srikanth, K. P.;Das, S.;Sharma, S.;Kumar, A.",2018,,http://dx.doi.org/10.1007/s12072-018-9852-3,0,0,
3393,Renal involvement in children with wilson's disease,"Background: Although renal involvement in Wilson's disease (WD) is rare, it is of significant importance due to the associated morbidity. Initially thought to be uncommon, recent data points to a more frequent occurrence of renal disease in children having Wilson's disease. However, very few studies have been done to elaborate this finding. The objective of our study is to describe the prevalence of associated renal disorders in children with WD. Method: It is a prospective observational study including patients aged 1-18 years, diagnosed before as WD, visiting the Liver clinic or admitted in the Pediatric ward of KEM Hospital, Pune. Patients with pre-existing renal disease were excluded. Demographic details, laboratory data and sonographic findings were recorded. Standard definitions were used for defining proteinuria, microscopic hematuria and hypercalciuria. Data was analysed using Mann Whitney U test and z score was calculated to know the significance of difference between the group with and without renal abnormalities. Result: Out of the 70 patients enrolled in our study, 4 children were excluded as they had pre-existing renal disease. Out of the 66 patients finally evaluated, 24 were girls and 42 were boys. Renal involvement usually occurred early in the course of illness and seemed to occur more frequently in children having WD at an earlier age. 60% of WD patients with renal manifestations had a positive Kayser-Fleischer (KF) ring. RTA was seen in 11 (16.6%), hematuria in 8 (12%), proteinuria (non-nephrotic) in 6 (9%), calculi in 5 (7.5%) and isolated hypercalciuria in 4 (6%) patients. There was no significant difference between WD patients having renal involvement and those without it, with respect to hepatic, neurological or combined hepatic and neurological presentation of WD. All the children were receiving Penicillamine, except two who were on Zinc maintenance therapy due to Penicillamine allergy. Despite extensive literature search, we found only two pediatric studies worldwide, which highlighted the renal aspect of WD. The most commonly associated renal abnormalities reported in those studies were hematuria, proteinuria and renal tubular acidosis with or without hypercalciuria. Conclusion: Ours is the only study from India shedding light on the unexplored renal aspect of WD in children. Further studies are required to formulate guidelines for screening of children with WD for renal abnormalities. [Table Presented].",adolescent;adult;allergy;child;controlled study;diagnosis;female;girl;hematuria;human;human tissue;hypercalciuria;India;infant;kidney malformation;kidney tubule acidosis;liver;maintenance therapy;major clinical study;male;observational study;pediatric ward;practice guideline;prevalence;prospective study;proteinuria;rank sum test;stone formation;Wilson disease;penicillamine;zinc;conference abstract,"Shah, V. S.;Katiyar, A.;Bhagat, N.;Sharma, J.;Bavdekar, A.",2018,,http://dx.doi.org/10.1007/s12072-018-9852-3,0,0,
3394,Transient elastography (fibroscan) assessment in patients with hepatic and neurological Wilson's disease,"Background: Non-invasive assessment of hepatic fibrosis with ultrasound based transient elastography (TE) (or fibroscan) has been validated in a number of chronic liver disease. However, studies involving Wilson disease (WD) patients are rare. Further studies comparing liver stiffness by TE in hepatic and neurological Wilson are lacking. Our aim was to assess liver stiffness by fibroscan in patients with hepatic and neurological Wilson's disease. Method: Twenty-five patients with well characterized WD underwent TE by FibroscanR, Echosens 402, Paris, France, software-B21). TE was performed in a right intercostal space in a resting respiratory position. Diagnosis of WD was made as per Leipzig criteria. All patients were on follow up and stable on treatment with D-penicil-lamine +/- zinc. The Fibroscan values were distinguished between hepatic and neurologic Wilson with regard to treatment & duration of illness. Continuous variables between groups were compared by unpaired t test. P value\0.05 was considered significant. Result: Twenty-five patients (13 with hepatic and 10 with neurologic and 2 with both) underwent TE 3-4 hours after breakfast. Seventeen were males. The mean age of the patients was 20 years and the mean duration of illness was 7.2 years. The demographic and laboratory characteristics between hepatic and neurologic WD are shown in Table. There was no statistical significance between the two in all variables except fibroscan scores.The fibroScan values in patients with neurological WD was 12.94+/-5.03 (Range 7-22) kPa and in those with hepatic WD was 26.7.6+/-16.06 (Range 12.2-75) kKa (p value = 0.003). Scores above 8.4 kPa are considered severe in WD. Conclusion: Patients with WD have advanced hepatic fibrosis on TE. Hepatic WD patients have significantly higher scores suggestive of cirrhosis while patients with neurologic WD have scores suggestive of severe fibrosis.",adult;clinical article;controlled study;diagnosis;drug therapy;elastograph;follow up;France;human;liver cirrhosis;liver fibrosis;liver stiffness;male;meal;nervous system;software;statistical significance;transient elastography;Wilson disease;young adult;zinc;conference abstract,"Joseph, T. S.;Devarbhavi, H.",2018,,http://dx.doi.org/10.1007/s12072-018-9852-3,0,0,
3395,Pediatric Hepatic Wilson Disease: Effect of chelation therapy and outcome in a large cohort,"Background: As there is paucity of exclusive literature on pediatric hepatic Wilson disease (WD), this study was aimed to evaluate clinical presentation and outcome of children with hepatic WD. Method: WD children satisfying > 2 of 3 criteria (serum cerulo-plasmin < 20 mg/dL, positive Kayser-Fleischer ring, 24 hour urine copper > 40)j.g) +/- liver histology managed in our department from Jan 2007 to June 2016 were analyzed. Patients with > 9 months of adequate follow-up were evaluated for response to chelation therapy. They were analyzed as following categories: a) complete improvement (asymptomatic + normalization of transaminases, serum albumin and coagulation); b) partial improvement (asymptomatic + near normalization of transaminases + serum albumin or coagulation) c) progression (deterioration of synthetic functions, decompensation or death); d) drug toxicity. To determine the prognostic factors of outcome, the follow-up cohort was divided into 2 groups a) Good outcome (> 9 months follow up with complete or partial improve-ment) and b) Poor outcome defined by worsening liver synthetic functions, need for liver transplantation, lost to follow-up within 9 months of starting therapy or death. Result: 111 WD children aged 108 (36-180) months and overall PELD score 16 (-11 to 60). Liver histology was consistent with WD in 68% (n = 27/40). Figure 1 shows the presentation and outcome.Chelation was started in 84% (n = 94). 14% (n =16) patients died in hospital due to advanced disease. 65with follow up of 43 (9-144) months were analyzed for outcome. 92% (n =60) were on D-penicillamine monotherapy and 6% (n = 4) with additional severe neurological presentation were on D-penicillamine and zinc. Among those on D-penicillamine monotherapy, favourable outcome was seen in 58% (n = 35). 13% (n =8) had drug toxicity and 12% (n = 7) required addition of zinc due to disease progression. 6% (n = 4) were started on trientine. Overall favourable outcome was observed in 70% (n = 46). Table 1 shows comparison of good and porr outcome patients. On logistic regression analysis, of all the variable PELD score and Nazar score were best predictors of outcome (p < 0.001). Conclusion: In this large pediatric experience of hepatic WD we have shown expanded clinical forms with various manifestations. Majority were manageable with D-penicillamine monotherapy. Addition or change of chelation is required in select situations of drug toxicity and neurological presentation. [Table Presented].",adult;adverse drug reaction;aged;chelation therapy;child;controlled study;death;deterioration;disease exacerbation;female;follow up;human;human tissue;liver histology;liver transplantation;major clinical study;male;monotherapy;remission;side effect;toxicity;urine;very elderly;Wilson disease;aminotransferase;ceruloplasmin;endogenous compound;penicillamine;serum albumin;trientine;zinc;conference abstract,"Sarma, M. S.;Das, M. C.;Yachha, S. K.;Srivastava, A.;Poddar, U.",2018,,http://dx.doi.org/10.1007/s12072-018-9852-3,0,0,
3396,"High efficacy of D-penicillamine in Wilson's disease: Contribution of noncompliance to the occurrence of D-penicillamine treatment ""failure""","Background: Wilson's disease (WD), a genetic disorder of copper metabolism due to the mutant ATP7B enzyme, is characterized by reduced excretion, disordered accumulation and abnormal deposits of copper cause the toxic damage to various organs. D-penicillamine(D-PCA) is an effective oral chelation agent for WD. Method: N/A. Result: A WD patient with clinical manifestations were reversed by D-PCA. However, the patient thought that he was healthy enough to lead to the administration of penicillamine being terminated. The reoccurrence of many manifestations of Wilson's disease were reported but the regular fellow-up were also stopped. In addition, his liver function after drinking alcohol started to deteriorate with the findings of symptoms such as progressive jaundice (yellowing of the skin and eyes), dark urine, fatigue, nausea, vomiting, migraine headaches, lower extremity edema, diarrhea. There was no signs of alleviation of Wilson's disease after taking a few pairs of Chinese herbs. Approximately 4 months after the administration of D-PCA treatment, improvement in jaundice and dysphoria, reduced serum levels of alanine aminotransferase, and elevated ceruloplasmin, as well as stabilization in the radiographic of neurologic and hepatic examination, were observe. Conclusion: Our case provides major recommendations for improving the compliance of WD patients and it is a lifelong challenge in terms of the management of WD.",adult;alcohol consumption;Chinese herb;clinical assessment;diarrhea;drug efficacy;dysphoria;edema;eye;fatigue;gene expression;human;human tissue;jaundice;liver function;male;migraine;nausea and vomiting;nervous system;nonhuman;protein blood level;skin;thinking;treatment failure;urine;Wilson disease;alanine aminotransferase;ceruloplasmin;endogenous compound;penicillamine;conference abstract,"Han, D.;Li, G.;Yan, T.;Sun, J.;Fan, W.",2018,,http://dx.doi.org/10.1007/s12072-018-9852-3,0,0,
3397,Phenotypic chracteristics and therapeutic multidisciplinary approach in Romanian patients diagnosed with Wilson's Disease,"Background: Wilson's disease (WD) is an autosomal recessive genetic disorder leading to hepatic and neurologic impairement. The aim of our study was to assess phenotypic and therapeutic particularities of WD patients treated in a tertiary hospital between 2012-2016. Methods: A retrospective study has been conducted including 88 patients diagnosed with WD during the defined period. Results: Age at diagnosis below 7 years was found in 12.9% of cases, between 7-18 years in 44.7%, 18-35years in 37.6% and >35years in 7%. At time of diagnosis, hepatic disease was found in 67%, hepatic and neurologic disease in 27.3%, exclusive neurologic disease in 5.7%. In patients with hepatic WD, 30.3% had compensated and 14.2% decompensated liver cirrhosis (LC), 50% chronic hepatitis, and 5.3% acute liver failure. In patients with hepatic and neurologic impairment, 66.6% had compensated and 11% decompensated LC and 22.2% chronic hepatitis. Exclusive hepatic disease was encountered in 77.7% of children in comparison to only 50% of adults (p=0.02). At last follow-up visit, treatment consisted in D-penicillamine 32.1%, trientine 8.3%, zinc 5.9%, D-penicillamine and zinc 41.7%, trientine and zinc 3.6%, liver transplantation being performed in 8.4% of cases. In patients with hepatic disease, clinical improvement was established in 65.8% of patients while worsening of disease in only 20.3%. In patients with hepatic and neurologic disease, clinical improvement was found in 59.1%, while worsening in 22.7%. Patients with isolated neurological impairment had a favorable clinical course in 75% of cases and the rest worsened. Conclusions: In a romanian tertiary center, WD with hepatic phenotype is the most frequently encountered especially in children and exclusive neurological disease is rare. A favorable disease course could be confirmed in >60% of cases in all phenotypes. During the study period, liver transplantation was performed in <9% of cases due to timely diagnosis and effective chelating therapy.",acute liver failure;adult;chelation;child;chronic hepatitis;decompensated liver cirrhosis;diagnosis;disease course;female;follow up;human;liver transplantation;major clinical study;male;phenotype;rest;retrospective study;Romanian (citizen);tertiary care center;Wilson disease;endogenous compound;penicillamine;trientine;zinc;conference abstract,"Iacob, R.;Oana, A.;Iacob, S.;Anghel, D.;Constantinescu, A.;Lupescu, I.;Popescu, I.;Gheorghe, L.",2017,,,0,0,
3398,Long-term outcome of neurological Wilson's disease,"Introduction: Aim of the study was to characterize the clinical spectrum of long-term treated patients with Wilson's disease (WD) and to identify risk factors influencing long-term outcome. Methods: In a cross-sectional study 30 WD-patients being treated for at least 2.5 and up to 31 years underwent a detailed clinical investigation, scoring of clinical findings yielding 7 motor and 3 non-motor subscores as well as laboratory testing. A factor analysis of these subscores and laboratory parameters was performed to detect those items with the highest influence on outcome, an ANOVA and subgroup analysis tested the influence of age, age at onset of diagnosis and duration of treatment on outcome. A correlation analysis was performed between clinical subscores and laboratory findings. Results: Three factors (F1-F3) characterized the clinical outcome (F1: tremor and pathological reflexes; F2: dystonia and dysarthria; F3: cerebellar abnormalities and gait), and three factors the laboratory findings (LF1: serum level of ceruloplasmin; LF2: liver enzymes; LF3: INR). Mildly affected patients had an elevated 24 h urinary copper excretion, more affected patients presented with elevated liver enzymes. Six of the 7 motor subscores did not change with duration of treatment, whereas tremor (p <.04), the total score (p <.02) and especially the non-motor items (p <.001) significantly increased with duration of treatment. The outcome of patients with neuropsychiatric abnormalities was significantly worse (p <.01) compared to the rest of the patients. Conclusions: Long-term outcome in WD is influenced by patient's compliance and neurological comorbidity. Copyright © 2018 Elsevier Ltd",Comorbidity;Compliance;Long-term outcome;Motor abnormalities;Non-motor abnormalities;Wilson's disease;adolescent;adult;article;bradykinesia;clinical article;clinical feature;clinical outcome;controlled study;cross-sectional study;disease severity;dysarthria;dystonia;female;gait disorder;human;hypertransaminasemia;international normalized ratio;long term care;male;onset age;pathological reflex;priority journal;protein blood level;risk factor;treatment duration;tremor;urinary excretion;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper;penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];trientine/cb [Drug Combination];trientine/dt [Drug Therapy];zinc/cb [Drug Combination];zinc/dt [Drug Therapy],"Hefter, H.;Tezayak, O.;Rosenthal, D.",2018,April,http://dx.doi.org/10.1016/j.parkreldis.2018.01.007,0,1,
3399,Bipolar affective disorder and wilson's disease: Case report and review of literature,"Background: There is limited data available regarding presentation of bipolar affective disorder in a case of Wilson's disease. Aim: To present Bipolar Affective Disorder, rapid cycling and Wilson's disease: case report Methodology (Case report): The index patient, Mr. A a 27 year old male who presented with features of overactivity, over cheerfulness, overspending, increased sociability, overfamiliarity, decreased sleep for 8 days duration in August 2017. On detailed evaluation patient had history of severe depressive episode with suicidal ideation, preceding the above symptoms for a duration of 5 months from April to August 2017. Preceding this depressive episode, a hypomanic episode was present in March 2017 lasting for a few days which was preceded by another depressive episode since January 2017. No euthymic intervening period was observed. There is past history of depressive episode in April 2014 lasting for 2 months. Patient was born of C-section with no perinatal complications. Patient had history of repeated episodes of jaundice at age of 9 years and was diagnosed with Wilson's disease. Patient was treated with Penicillamine-d and was later added Zinc supplementation. Patient's symptoms of Wilson's worsened during June-July 2017 requiring inpatient management in Neurology, though it was not corroborated with change in investigative parameters. Patient continues to be on Baclofen and Zinconia for treatment of Wilson's. On physical examination patient had dystonia, incoordination, dysphagia. Patient's current blood investigations revealed normal blood counts and liver function tests and Serum copper. Patient was started on Tablet Oxcarbazepine upto 1200mg/day and and Tablet Quetiapine upto 600mg/day with no change in symptoms over 3 weeks and Tablet Lithium carbonate was added. Treatment for Wilson's disease was continued as per Neurologist opinion. Patient followed up after 2 weeks with improvement in presenting complaints.",Bipolar disorder;rapid cycling;Wilson's Disease;adult;blood cell count;child;clinical evaluation;coordination disorder;copper blood level;diagnosis;drug combination;drug therapy;dysphagia;dystonia;hospital patient;human;human tissue;hypomania;jaundice;literature;liver function test;male;neurologist;neurology;newborn disease;physical examination;school child;sleep;suicidal ideation;systematic review;tablet;Wilson disease;baclofen;lithium carbonate;oxcarbazepine;penicillamine;quetiapine;zinc;conference abstract,"Poornima Rao, S.;Rajpal, N.;Bali, S.;Kau, N.",2018,February,,0,0,
3400,Wilson's disease (hepato-lenticular degeneration),"Background: Wilson's disease is a neuropsychiatric-autosomal recessive illness characterized by excessive accumulation of copper predominantly in liver and different parts of brain namely-basal ganglia, midbrain and pons. Genetic defect is attributed to a membrane bound copper binding protein gene-ATP7B (on chromosome 13), which incorporates copper in ceruloplasmin. Impaired elimination of copper leads to its accumulation and resulting clinical features. Patient can present with tremors, dystonia, rigidity, dysarthria, brisk refexes and psychological and behavioural disturbances. Neurological and psychiatric symptoms can occur at any point in the course of the disease. We report a case of Wilson's disease in a 26 year old female, presenting with psychiatric symptoms. Case Summary: 26 year old female, with history of tremors, diffculty in walking and speaking since 10 years of age presented with complaints of feeling naked despite wearing clothes, sensation of touch when alone and disturbed sleep since 4 months. Mental status examination revealed tactile hallucinations, ideas of reference, anxiety and dysphoric mood. Neurological examination revealed tremors, rigidity in upper extremities, dysarthria, poor coordination and brisk deep tendon refexes. Ophthalmological examination revealed prominent Kayser-Fleischer rings in both eyes. The patient had ceruloplasmin level of <0. 08 g/L, serum copper level of 29. 3 mcg/dl, liver function test revealed alkaline phosphatase levels of 144 U/L. MRI brain reported focal areas of T2/FLAIR hyper-intensities involving bilateral thalami, midbrain and pons and mild cerebral atrophy significant for age. Other investigations like renal function test, lipid profile and thyroid profile were found to be within normal limits. Patient is currently on treatment with Penicillamine, Zinc Supplementation and Olanzapine. Psychoeducation was given to family members. Significant improvement has been observed with treatment.",Ceruloplasmin;Dysarthria;Dystonia;Kayser-Fleischer ring;adult;anxiety;brain atrophy;case report;clinical article;clothing;coordination;copper blood level;drug therapy;eye;female;gene expression;hallucination;human;human tissue;kidney function test;liver function test;mental health;mesencephalon;mood;neurologic examination;nuclear magnetic resonance imaging;pons;psychoeducation;rigidity;sensation;sleep;tendon;touch;tremor;upper limb;walking;Wilson disease;alkaline phosphatase;endogenous compound;lipid;olanzapine;penicillamine;zinc;conference abstract,"Khan, A. A. B.;Chaudhari, S. B.",2018,February,,0,0,
3401,Case report-wilson's disease presenting as psychiatric disorder,"Wilson disease is an autosomal recessive metabolic disorder involving copper metabolism and is associated with abnormal liver functions. It is a genetic disorder with hepatic, neurological and psychiatric manifestations. The most common psychiatric manifestations in patients with Wilson's disease include sudden and changeable mood swings, anger outbursts, personality changes, depression, anxiety and cognitive impairment. when patient initially presents with psychiatric manifestations, it can obscure the primary diagnosis and therefore the diagnosis of Wilson's disease should be kept in mind. here we present the case of 22yr old male initially presented with behavioural abnormalities and later was diagnosed to be Wilson's disease. Introduction: Dr. Wilson published description of 12 patients who presented with extrapyramidal motor disease and an autopsy demonstrating softening of lenticular nucleus and cirrhosis. In the initial description of 12 cases of the disease, Dr Wilson described presence of schizophrenia-like psychosis in two of his cases. Psychiatric symptoms ranging from major depression, mania, antisocial behaviour to psychoses were observed in cases with Wilson's disease. It is later found to be a genetic disorder transmitted through autosomal recessive mode and involving copper metabolism characterised by excessive deposition of copper in liver, brain and other tissue. Genetic defect was localised to short arm of chromosome 13 affecting ATPase(ATP7B)1 gene in liver presenting with hepatic manifestations(40%), neurologic manifestations(40%), psychiatric manifestations occur in one ffth2. Neuropsychiatric and behavioural disturbances are commonly reported in patients with Wilson's disease with lifetime prevalence estimated to be in the range of 20-100%. We present a case report in which the patient initially presented with psychotic features, who on investigations found to have Wilson's disease. Case Report: A 22year old male born out of non-consanguineous marriage from rural background was brought to psychiatry out patient department of Government Hospital for Mental Care, Visakhapatnam with complaints of behavioural abnormalities since one week with exacerbation of symptoms since 3 days. The behavioural abnormalities are in the form of decreased sleep, decreased appetite, increased irritability, talking excessively, over socialisation, talking high of self, increased religiosity, increased patriotism, abusive and aggressive behaviour. He was reportedly treated for aggression with inj. Haloperidol the day before he came to us. Birth and development were normal with no significant past history. In family history his elder brother was found dead in the felds at the age of 10 years and was asssumed to be dead due to some snake bite. His younger sister died due to jaundice and ascites at the age of 13years. Prior to illness, he is a cheerful boy, with average performance at school and regular to school. General physical examination revealed normal vital parameters with no icterus, a ring around his cornea, tatoo of Indian map with cross inside it on his left forearm. Higher mental functions revealed impaired attention span. He is well oriented to time, place, person and his recent/immediate/remote memory were found to be intact with impaired abstract abilities. his Neurological examination revealed no abnormalities in cranial nerves, sensory system and no cerebellar signs with motor system revealing tremors on out stretched hand. At the time of admission mental status examination revealed an averagely built male, wearing soiled white uniform with tie and greeted the examiner as teacher and saluted the examiner. He was conscious, uncooperative, not maintaining eye contact with increased psychomotor activity with decreased reaction time, talking excessively in loud voice. Delusion of grandiosity and second person type auditory hallucination are present. He was found to be irritable throughout the interview. routine blood investigations like CBC, LFT, S. Creatine, urine routine were done and found to be normal. He was provisionally diagnosed as a case of bipolar affective disorder-mania and was initially started on oral olanzapine and injectable antipsychotics. Later the patient developed tremors and slurring of speech for which trihexyphenidyl was added and for the improvement of affective symptoms lithium carbonate was added. In view of significant family history and acute onset of behavioural abnormalities further work up on case was done with differential diagnosis of Wilson's disease. On developmental screening test, his IQ was 84 with dull normal intellectual functioning. On slit lamp examination bilateral KF rings are present. His ultrasound abdomen showed chronic hepatic parenchymatous disease. His MRI brain showed subcortical white matter hyperintensity in left frontal lobe, calcifed high right parietal lobe granuloma and bilateral lentiform nucleus T2 and FLAIR hyperintensity suggestive of Wilson's disease. Urinary analysis revealed elevated copper levels of 108mu g/24hrs and serum ceruloplasmin levels of. 46g/l. he was maintained on olanzapine 15 mg, 6mg of trihexyphenidyl, 900mg of lithium carbonate and 400mg zinc sulphate. He improved symptomatically with the treatment, was discharged with the same treatment. Discussion: Wilson's is a autosomal recessive disorder characterised by inability of liver to transport and store normally absorbed dietary copper resulting in abnormal deposition of copper in basal ganglia, eyes, liver and other tissues. This is an unusual presentation of Wilson's disease, here the patient had a history of abnormal behaviour for 7 days and with significant family history and a differential diagnosis of Wilson's disease was considered and on further evaluation he was diagnosed with Wilson's disease. The patient was controlled on 15 mg of olanzapine and 900mg lithium carbonate. Some authorities believe that neurological and behavioural symptoms can be relieved with use of pencillamaine (mosai et al 1985). some reports stated antipsychotic use as inadvisable. There are reports of effectiveness of clozapine in management of wilsons disease (krim et al 2001). There is further need to study the effcacy if various antipsychotics and chelating agents in the management of wilsons disease.",Psychiatric Disorder;Wilsons disease;abdomen;abnormal behavior;adolescent;adult;aged;anger;antisocial behavior;anxiety;ascites;attention;auditory hallucination;autopsy;basal ganglion;bipolar disorder;brother;case report;ceruloplasmin blood level;child;chromosome 13;clinical article;cognitive defect;congenital malformation;copper metabolism;cornea;cranial nerve;decreased appetite;delusion;developmental screening;diagnosis;diet;differential diagnosis;disease exacerbation;drug combination;emotional disorder;family history;female;forearm;frontal lobe;government;granuloma;human;human tissue;interview;irritability;jaundice;liver cirrhosis;long term memory;major depression;male;marriage;motor system;neurologic examination;nuclear magnetic resonance imaging;outpatient;parietal lobe;physical examination;prevalence;psychiatry;psychosis;reaction time;school child;short term memory;sleep;slit lamp microscopy;snakebite;speech;teacher;tremor;ultrasound;urinalysis;voice;white matter;Wilson disease;young adult;chelating agent;clozapine;creatine;endogenous compound;haloperidol;lithium carbonate;olanzapine;trihexyphenidyl;Wilson disease protein;zinc sulfate;conference abstract,"Jetty, R. R.;Suresh Kumar, G.;Himakar, P.",2018,February,,0,0,
3402,"Copper chelation in hypertrophic cardiomyopathy; open-label pilot study assessing the effects of trientine on LV mass, myocardial fibrosis, performance and metabolism","Background: HCM is the most inherited cardiomyopathy but as yet no pharmacological intervention has ever proven to alter the natural history or outcome of the disease, with a pressing need for a new impetus in this field. Furthermore, CMR appears ideally placed to characterise many of the key pathophysiological processes dominating the disease. Copper (Cu) is an essential cofactor for a variety of metabolic functions and whilst regulation of systemic Cu metabolism is critical to human health, free Cu ions are extremely redox-active and thus potentially toxic. We previously reported abnormal copper homeostasis in patients with HCM. In brief we found significantly elevated serum (free) copper and coeruloplasmin levels in HCM patients compared to controls. Given that disturbances of Cu homeostasis can lead to hypertrophic forms of heart disease (e.g. in Wilson disease) and given that we previously demonstrated that Cu chelation in absence of Cu deficiency is able to reverse LVH and organ fibrosis via Cu-dependent mechanism both in animal and human studies we hypothesised that Cu-selective chelation with trientine would slow disease progression in HCM. Methods: This open-label, pilot study explored the clinical efficacy and tolerability of trientine dihydrochloride in a group of 20 patients with HCM, over a 6-month period. Pre-defined endpoints included changes in LVM, markers of LV fibrosis, markers of LV performance and myocardial energetics. 10 further matched HCM patients were studied as controls. Patients underwent a complex assessment schedule during 6 visits including separate CMR and CMR 31P-spectroscopy at baseline and end of therapy. Results: Trientine induced no significant change in BP, HR or BMI. LV Mass decreased significantly in the treatment arm compared to the control group (-4.2g v 1.8g, p=0.03). A trend towards an absolute decrease in mass was observed in the treatment group (p=0.06). These changes were associated with a reduction in native T1 (1060+/-47ms vs 1049+/-42ms, p=0.06) and a reduction in ECV (30.0+/-4.5% v 29.5+/-4.0%, p=0.06). Furthermore, significant improvements were seen in global longitudinal strain using both Echo speckle tracking based and CMR feature tracking based technologies (-16.6+/-4.3 vs -18.9+/-4.4, p=0.01 and -18.3+/-3.4 vs -19.4+/-3.4, p=0.03 respectively). Equally, significant improvements were noted in atrial strain parameters, again with mirror changes between both imaging technologies. There was a trend towards increase in PCr/ATP ratio with trientine therapy (1.27+/-0.44 vs 1.4+/-0.39), however this did not reach statistical significance. No significant increase in exercise time, VO2max or AT was observed. Conclusion: Cu-selective chelation with trientine in a controlled environment is safe and appears to have beneficial effects on several disease imaging biomarkers. Indeed, it appears to at least slow disease progression. A larger Phase 2b double blind randomised trial is now warranted.",adult;aerobic capacity;animal experiment;animal model;animal tissue;body mass;chelation;controlled study;copper deficiency;disease exacerbation;double blind procedure;drug therapy;exercise;female;gene expression;heart muscle fibrosis;homeostasis;human;hypertrophic cardiomyopathy;male;nonhuman;phase 2 clinical trial;pilot study;spectroscopy;statistical significance;Wilson disease;adenosine triphosphate;biological marker;ceruloplasmin;copper;endogenous compound;trientine;conference abstract,"Reid, A.;Miller, C.;Cooper, G.;Schmitt, M.",2017,August,http://dx.doi.org/10.1093/eurheartj/ehx502.P4503,0,0,
3403,"WTX101 in patients newly diagnosed with Wilson disease: Final results of a global, prospective phase 2 trial","Background and Aims: Current therapies for Wilson disease, a disorder of copper metabolism resulting from ATP7B protein absence or dysfunction, are limited by efficacy, safety and multiple daily dosing. WTX101 (bis-choline tetrathiomolybdate) is a first-in-class copper-modulating oral agent that acts by increasing biliary copper excretion and reducing non-ceruloplasmin bound serum copper (NCC) by forming complexes with albumin. Methods: In an open-label, single-arm, phase 2 study, 28 newly diagnosed patients withWilson disease (aged 18-64 years, 46% male, 89% with some degree of neurological symptoms and around 50% with cirrhosis at baseline) received WTX101 monotherapy using a response-guided dosing regimen with individualised doses of 15-120 mg/day, mostly once daily. The primary endpoint was change from baseline to 24 weeks in NCC levels corrected for copper in tripartite tetrathiomolybdate-copper-albumin complexes in treated patients (NCCc). Model for End-stage Liver Disease (MELD) and modified Nazer Score were used to monitor stability of liver disease and safety. Neurological status was evaluated using the Unified Wilson Disease Rating Scale (UWDRS). Results: At 24 weeks, 71% of patients treated with WTX101 either achieved or maintained normalised levels of NCCc or experienced a >=25% reduction from baseline NCCc (p < 0.001). Mean NCCc was significantly reduced from 3.6 uM at baseline to 0.9 uM at week 24 (p < 0.0001). Mean MELD score and modified Nazer score remained stable over the course of treatment indicating stabilisation of liver function. Reversible asymptomatic liver test elevations, observed in 39% of patients (at 30 mg/day dose or higher), were generally mild to moderate, and normalised with dose adjustments. Compared with baseline, patients showed significant improvements at week 24 in mean UWDRS disability score (6.6 vs. 4.1, p < 0.001) and neurological symptom score (22.8 vs. 16.6, p < 0.0001). No initial drug-induced neurological worsening was seen. Conclusions: Final data from the first global, prospective clinical trial in Wilson disease indicate that WTX101 rapidly lowered and controlled NCCc resulting in improved disability and neurological status, with stable liver function and a favourable safety profile. These findings, together with its simple dosing regimen, indicate that WTX101 has the potential to address several unmet needs in the treatment of Wilson disease.",adult;animal experiment;animal model;animal tissue;controlled clinical trial;controlled study;copper blood level;diagnosis;disability;end stage liver disease;female;human;liver cirrhosis;liver function;male;Model For End Stage Liver Disease Score;monotherapy;nonhuman;phase 2 clinical trial;prospective study;rating scale;Wilson disease;albumin;endogenous compound;conference abstract,"Weiss, K. H.;Askari, F. K.;Ferenci, P.;Ala, A.;Czlonkowska, A.;Nicholl, D.;Bronstein, J.;Bega, D.;Schilsky, M. L.",2017,,,0,0,
3404,"Predicting ""poor outcome"" in decompensated wilson's disease: Does new wilson's index helps?","Background and Aims: Recently there are conflicting reports about the efficacy of New Wilson's index (NWI) in predicting outcome of Wilson's disease (WD), which is the only available prognostic model in WD. We thus aimed to study the prognostic value of NWI. Methods: Retrospective evaluation of eighty cases of WD presenting to this centre from year 2011 to 2016 was done, amongst which 71 were either acute on chronic liver failure (ACLF) or decompensated CLD. They were managed with supportive care along with combination of D Pencillamine and Zinc. Univariate and multivariate analysis was done to see the association of the risk factors with poor outcome (liver transplantation or death) anytime during hospital stay. Results: Of the 71 WD cases, 43 survived on medical management: 7 of 22 ACLFand 36 of 49 decompensated CLD. Fifteen of 22 ACLFand 13 of 49 decompensated CLD had poor outcome. On univariate analysis, bilirubin (Mean difference 11.47, 95% CI 6.7-16.2, p = 0.00), AST (Mean difference 160.8, 95% CI 64.8-256, p = 0.001), INR (Mean difference 1.63, 95% CI 0.93-2.33, p = 0.00), NWI (Mean difference 5.37, 95% CI 3.67-7.08, p = 0.00), Pediatric end stage liver disease (PELD) score (Mean difference 11.47, 95% CI 6.7-16.2, p = 0.00), presentation as ACLF (odd's ratio or OR 5.93, 95% CI 1.97-17.8, p = 0.001) and hepatic encephalopathy (HE) grade 3 or 4 (OR 48.5, 95% CI 5.8-402.7, p = 0.00) were significantly associated with poor outcome. On logistic regression analysis significant association with poor outcome was seen with HE grade 3/4 (adjusted OR 33.47, 95% CI 3.6-310.4, p = 0.002) and PELD score (adjusted OR 8.3, 95% CI 1.9-35.1, p = 0.004). On further subjecting, the group with no HE or HE grade 1 or 2 to binary logistic analysis, PELD score was significantly (adjusted OR 11.4, 95% CI 2.2-59.2, p = 0.004) associated with poor outcome. ROC analysis revealed PELD score best cutoff of 17.5 to identify poor outcome with the sensitivity of 84.5% and specificity of 69% in patients with (AUROC = 0.843) or without HE (AUROC = 0.812). Conclusions: HE grade 3/4 and high PELD (>17.5) are independently associated with poor outcome in decompensated WD. NWI did not show significant independent association with poor outcome. Further studies are required to develop optimum prognostication models for WD.",acute on chronic liver failure;animal experiment;animal model;aspartate aminotransferase level;death;diagnostic test accuracy study;end stage liver disease;female;hepatic encephalopathy;hospitalization;human;international normalized ratio;liver transplantation;male;Model For End Stage Liver Disease Score;multivariate analysis;nonhuman;receiver operating characteristic;retrospective study;risk factor;univariate analysis;Wilson disease;bilirubin;zinc;conference abstract,"Alam, S.;Sood, V.;Khanna, R.;Lal, B. B.;Rawat, D.",2017,,,0,0,
3405,Clinical efficacy and safety of Gandouling plus low-dose D-penicillamine for treatment of Wilson's disease with neurological symptoms,"To investigate the effect and safety of Gandouling plus low-dose D-penicillamine for treating patients with Wilson's disease (WD) who have neurological symptoms. WD patients with neurological symptoms were divided into two groups: a treatment group (n=53) and a control group (n=50). The treatment group received anti-copper therapy with a combination of Gandouling and low-dose D-penicillamine (10 mg/kg), whereas the control group was with conventional dose D-penicillamine (20 mg/kg) monotherapy. The clinical efficacies, adverse reactions, and results of the various hematological and biochemical investigations were recorded and analyzed statistically. Overall, 98.11% of the WD patients treated with the combined therapy experienced alleviation of their neurological condition (paralleled by a significantly improved Global Assessment Scale score or remained stable). Their white blood cell and platelet counts stabilized, and their liver function was improved or remained stable. The combined therapy also obviously promoted improved 24-h urinary copper excretion. Only 15.09% of the WD patients with the combined therapy experienced adverse reactions, including neurological deterioration in one case (1.89%) and hepatic worsening in one case (1.89%), which was less frequent than that in the control group given conventional-dose D-penicillamine monotherapy. Treating WD patients with neurological symptoms using Gandouling plus low-dose D-penicillamine is effective and safe. Copyright © 2018 JTCM. All rights reserved.",Gandouling;Hepatolenticular degeneration;Neurologic manifestations;Penicillaminate;abdominal discomfort/si [Side Effect];adult;alanine aminotransferase blood level;appetite disorder/si [Side Effect];arthralgia/si [Side Effect];article;aspartate aminotransferase blood level;bilirubin blood level;ceruloplasmin blood level;controlled clinical trial;controlled study;disease association;drug dose increase;drug efficacy;drug safety;female;Global Assessment of Functioning;human;leukocyte count;leukopenia/si [Side Effect];liver disease/si [Side Effect];liver function;low drug dose;major clinical study;male;mental deterioration/si [Side Effect];monotherapy;neurologic disease/dt [Drug Therapy];platelet count;prothrombin time;urinary excretion;Wilson disease/dt [Drug Therapy];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];Chinese drug/ae [Adverse Drug Reaction];Chinese drug/ct [Clinical Trial];Chinese drug/cb [Drug Combination];Chinese drug/dt [Drug Therapy];copper;penicillamine/ae [Adverse Drug Reaction];penicillamine/ct [Clinical Trial];penicillamine/cb [Drug Combination];penicillamine/dt [Drug Therapy];unclassified drug;gandouling/ae [Adverse Drug Reaction];gandouling/ct [Clinical Trial];gandouling/cb [Drug Combination];gandouling/dt [Drug Therapy],"Zhang, J.;Li, L.;Chen, H.;Yang, W.",2018,15 Feb,,0,1,
3406,Hepatic sarcodosis presenting as portal hypertension in a young boy,"A 13-year-old boy, known case renal stone disease came with the complaints of abdominal pain along with low grade fever. On examination, hepatosplenomegaly was noted while his lab reports showed a low hemoglobulin with a raised ESR. His blood and urine cultures showed no growth. Viral markers, autoimmune profile, C and p ANCA were all negative apart from a raised serum IgG level. Ultrasound abdomen showed a hyperechoic liver with an enlarged spleen along with splenic varices and minimum ascites. Ultrasound hepatic doppler was normal. Serum AFP levels were normal while workup for Wilson's disease was negative. Fibroscan showed F4 fibosis. CT scan abdomen showed an enlarged left lobe of the liver along with an enlarged spleen. His EGD revealed varices. So liver biopsy was done that was suggestive of chronic granulomatous disease with ZN stain testing negative for TB.PPD, urine for AFB were both negative. Serum ACE levels were raised. He started ATT therapy but his condition did not improve. So, on the suspicion of hepatic sarcoidosis, he started on steroids and had a drastic improvement in his condition. Copyright © 2018 RIGLD.",Chronic granulomatous disease;Hepatic sarcoidosis;Serum ace levels;Steroids;abdominal pain;adolescent;article;case report;clinical article;elastography;erythrocyte sedimentation rate;fever;fibrosis;gastrointestinal endoscopy;hepatic sarcoidosis/dt [Drug Therapy];hepatomegaly/di [Diagnosis];hepatosplenomegaly;human;human cell;human tissue;inflammatory cell;liver biopsy;lymphocytic infiltration;male;nephrolithiasis;portal hypertension;sarcoidosis/dt [Drug Therapy];splenomegaly/di [Diagnosis];steroid therapy;X ray computed tomography;alpha fetoprotein/ec [Endogenous Compound];hemoglobin/ec [Endogenous Compound];immunoglobulin G/ec [Endogenous Compound];steroid/dt [Drug Therapy];tuberculostatic agent,"Achakzai, I. K.;Majid, Z.;Khalid, M. A.;Khan, S. A.;Laeeq, S. M.;Luck, N. H.",2018,01 Dec,http://dx.doi.org/10.22037/ghfbb.v0i0.1288,0,0,
3407,Recent Trends of Trace Element Studies in Clinical Medicine in Japan. [Japanese],"The deficiency or excess intake of trace elements, including zinc, copper, selenium and iodine, has often been reported. Zinc deficiency is often observed in infants fed breast milk with low zinc concentration, individuals administered chelating medicines, athletes and patients with diabetes mellitus, hepatic cirrhosis or nephrosis syndrome. Menkes disease is associated with severe copper deficiency, and there is no effective treatment. Deficiencies of selenium and iodine are observed in patients who receive special formulas of milk and enteral formula with low selenium and iodine concentrations, respectively. In contrast, neonatal transient hypothyroidism due to excess intake of iodine in pregnant women has also reported in Japan. It is expected that collaborative studies by researchers and clinicians will contribute to clarify the detail mechanism, diagnosis and treatment of these abnormalities.",clinical medicne;copper;deficiency;iodine;selenium;zinc;clinical medicine;female;human;hypothyroidism;Japan;male;Menkes syndrome;newborn;pregnancy;Wilson disease;trace element;trends,"Kodama, H.",2018,,http://dx.doi.org/10.1265/jjh.73.75,0,0,
3408,A case of acquired hepatocerebral degeneration presenting as hemichorea post-liver transplant,"Acquired hepatocerebral degeneration (AHCD) is a rare but morbid neurological manifestation of decompensated cirrhosis. Portosystemic shunting leads to manganese deposition in the basal ganglion which is identified as bilateral hyperintense signals on T1-weighted MRI. The resulting neuronal loss leads to involuntary movements, cognitive dysfunction, Parkinsonism, or cerebellar ataxia in the absence of hepatic encephalopathy. We present a case of AHCD with several unique features: 1) initial presentation post-liver transplant (OLT), 2) no clinical or radiographical evidence of portosystemic shunting, and 3) unilateral basal ganglia hyperintensity. A 57-year-old man with hypertension and chronic kidney disease (stage III) underwent OLT for hepatitis C and alcoholic cirrhosis 3 years prior to presentation. His post-transplant course was complicated by continued alcohol abuse, steroid-induced hyperglycemia, and acute cellular rejection without fibrosis 4 months prior. Prescriptions included tacrolimus, mycophenolate mofetil, prednisone, nifedipine, and insulin with questionable adherence. He had no personal or family history of movement disorders. His chief complaint was one month of progressive, uncontrollable right-sided arm and leg movements in a writhing, non-rhythmic pattern. He was afebrile. Physical exam was notable for rightsided hemichorea with normal strength, finger-to-nose test, reflexes, and sensation. He displayed no altered-mental status, asterixis, nystagmus, hepatosplenomegaly or ascites. Labs were notable for total bilirubin 1.3 mg/dL, Alk Phos 43 U/L, AST/ALT 117/65 U/L, blood alchohol level 103 mg/dL. INR 1.0 and platelets 141 x103/mu L. Electrolytes, glucose and creatinine were normal. HgbA1c 6.0%. Tacrolimus level undetectable. Serum iron, zinc, lead, and manganese levels were normal. MRI brain notable for T1 hyperintensities in the left globus pallidus without evidence of hemorrhage or acute ischemia (Figure 1). He was treated with haloperidol 1mg twice daily which mildly suppressed the hemichorea and allowed discharge with close neurology follow-up. Symptoms of ACHD often improve with resolution of portosystemic shunting post-OLT. However, we present a case of new onset ACHD in a posttransplant patient without evidence of portosystemic shunting. This illustrates that ACHD remains a poorly understood disorder that should be considered in patients with typical findings and a history of cirrhosis, even after liver transplantation. (Figure Presented).",acute graft rejection;adult;alcohol abuse;alcohol liver cirrhosis;arm movement;ascites;aspartate aminotransferase level;bleeding;case report;cerebellar ataxia;chronic kidney failure;clinical article;cognitive defect;drug therapy;family history;fibrosis;finger;flapping tremor;follow up;globus pallidus;hepatic encephalopathy;hepatitis C;hepatosplenomegaly;human;human cell;human tissue;hyperglycemia;hypertension;international normalized ratio;involuntary movement;iron blood level;ischemia;leg movement;liver graft;male;mental health;middle aged;neurology;nose;nuclear magnetic resonance imaging;optokinetic nystagmus;parkinsonism;physical examination;portosystemic anastomosis;prescription;reflex;sensation;thrombocyte;Wilson disease;bilirubin;creatinine;electrolyte;glucose;haloperidol;hemoglobin A1c;insulin;manganese;mycophenolate mofetil;nifedipine;prednisone;tacrolimus;zinc;conference abstract,"Lappas, B. M.;Choksi, Y.;Porayko, M. K.",2017,October,http://dx.doi.org/10.1038/ajg.2017.321,0,0,
3409,Incidental diagnosis of wilson's disease: A case report,"Wilson's disease (WD) is a genetic disorder of copper metabolism caused by complete absence or dysfunction of a copper transporting enzyme which is a transmembrane protein ATPase (ATP7B) encoded on chromosome 13. The incidence of this condition is seen in 1 in 30 000 individuals. The presentation of WD is variable and usually involves the hepatic and neuropsychiatric systems with symptoms ranging from chronic liver disease, compensated or decompensated cirrhosis, fulminant liver failure, dystonia, choreiform movements, tremor, gait disturbances, personality changes and cognitive impairments which are attributed to copper accumulation. We present a case where routine imaging for a persistent problem considered to be chronic pelvic pain led to the diagnosis of WD. A 28-year-old female with history of longstanding depression and Type 1 Diabetes Mellitus was admitted with recurrent abdominopelvic pain. She had been hospitalized multiple times for evaluation of recurrent abdominopelvic pain. Her initial episode of abdominopelvic pain was evaluated with a CT Abdomen that showed a pelvic abscess which was managed surgically with complete resolution and since then, she has had extensive evaluation including serial imaging during subsequent hospitalizations which were negative for any acute process. During this admission, a repeat CT Abdomen showed new onset cirrhosis of the liver which was absent on previous imaging studies. Patient denied alcohol use and after a negative infectious, autoimmune and hematological workup, further laboratory evaluation showed low serum levels of ceruloplasmin (5.4 mg/dl) and an elevated 24 hour urine copper excretion (302 ug/d). Slit light examination of the eyes was negative for Kayser-Fleisher rings. MRI Brain showed T2 high signal intensity in the pons. She was empirically started on zinc gluconate. Genetic testing showed heterozygous mutation in the gene ATP7B and a diagnosis of Wilson's disease was made. Patient continues to be maintained on zinc therapy and is closely being followed as an outpatient for liver transplant evaluation. The diagnosis of WD can be easily missed and if diagnosed early could potentially prevent or reverse many of its serious manifestations. Despite the involvement of the hepatic and neurological system on imaging, our patient was completely asymptomatic which makes this case unique. Our case further reiterates the importance of always keeping WD on the differential in evaluating patients with cirrhosis. (Figure Presented).",abdomen;adult;alcohol consumption;case report;clinical article;clinical evaluation;diagnosis;drug therapy;excretion;eye;female;gene expression;gene mutation;genetic association;genetic screening;heterozygosity;hospitalization;human;human tissue;insulin dependent diabetes mellitus;liver cirrhosis;liver graft;nuclear magnetic resonance imaging;outpatient;pelvis abscess;pelvis pain syndrome;pons;protein blood level;remission;surgery;urine;Wilson disease;ceruloplasmin;endogenous compound;gluconate zinc;Wilson disease protein;zinc;conference abstract,"Aleem, A.;Khan, J.;Bloomfield, C.",2017,October,http://dx.doi.org/10.1038/ajg.2017.351,0,0,
3410,Deployed sailor with an acute presentation of Wilson disease,"A 23 year old previously healthy US Sailor was evacuated from Bahrain after presenting to a local hospital with dyspnea on exertion, abdominal swelling, jaundice, cognitive decline, and months of fatigue. Patient had no past medical or surgical history and was an infrequent drinker. Family history was notable for an uncle with schizophrenia who died of cirrhosis presumed to be from alcohol in his early 40s. Examination demonstrated hypomimia, bradyphrenia, bradykinesia, Kayser-Fleischer rings, jaundice, new ascites, but no asterixis. Labs were notable for pancytopenia with platelets of 37K, an absolute neutrophil count (ANC) 111, and a coombs negative hemolytic anemia. Alkaline phosphatase was 133, Aspartate aminotransferase was 81, Alanine aminotransferase was 57, and total bilirubin was 1.9. Presentation INR was 2.8, with a calculated MELD sodium of 26. A contrast MRI showed multiple basal ganglia signal abnormalities. On arrival in Germany, ceruloplasmin was low at 8 mg/dL. 24 hour urine copper collection was performed and treatment was subsequently initiated with oral zinc based on a presumptive diagnosis of Wilson disease. Subsequent transjugular liver biopsy was performed with an elevated HVPG of 12 confirming portal hypertension. Small esophageal varices were noted on EGD. Wilson disease is a rare autosomal recessive disease with a worldwide incidence approaching 1 in 30,000 that results from copper accumulation and injury to affected tissues. Defects in the ATP7B gene, which encodes transmembrane transport of copper within hepatocytes, play a role in the disease. Key clinical features include liver disease, neuropsychiatric changes, Kayser-Fleischer rings, and coombs negative hemolytic anemia. However, given significant variability in disease presentation, both the European Association for the Study of Liver Disease (EASL) and the American Association for the Surgery of Liver Disease (AASLD) have proposed criteria to aid in diagnosis. Using the EASL criteria, the diagnosis was made approximately 8 days earlier, although ultimately the patient met the requirements from both societies. This atypical presentation of jaundice and constitutional symptoms in a deployed sailor highlights the potential advantages of the EASL criteria which do not require 24 hour urine copper which is not readily accessible in a deployed setting.",abdominal swelling;adult;ascites;Bahrain;basal ganglion;bradykinesia;bradyphrenia;clinical feature;cognitive defect;congenital malformation;diagnosis;dyspnea;esophagus varices;family history;fatigue;flapping tremor;Germany;hemolytic anemia;human;human cell;human tissue;incidence;injury;international normalized ratio;jaundice;liver biopsy;liver cirrhosis;liver disease;low drug dose;male;neutrophil count;nuclear magnetic resonance imaging;organization;pancytopenia;portal hypertension;sailor;schizophrenia;surgery;thrombocyte;uncle;urine;Wilson disease;young adult;alanine aminotransferase;alcohol;alkaline phosphatase;aspartate aminotransferase;bilirubin;ceruloplasmin;endogenous compound;sodium;Wilson disease protein;zinc;conference abstract,"Bridges, E. E.;Junga, Z.;Cusmano, P. M.;Torres, D. M.",2017,October,http://dx.doi.org/10.1038/ajg.2017.351,0,0,
3411,Copper failure in Wilson and Alzheimer disease,"Copper failure is the cause of Wilson disease (WD), a rare disorder typified by increased levels of copper nonbound to ceruloplasmin (non-Cp Cu) and copper-ceruloplasmin ratio (Cu:Cp). Meta-analyses also show copper abnormalities in Alzheimer disease (AD); however, a direct comparison of copper biological status in the two diseases has never been carried out. An investigation of copper status in serum (copper, ceruloplasmin, non-Cp Cu and Cu:Cp, adjusting for sex and age) and a 24-hour copper urine assessment of patients with AD, WD (nine WD patients at baseline and 24 WD patients under D-penicillamine [D-pen] treatment)], and healthy controls (35 healthy controls) was carried out. In a sample of 385 AD cases and 336 healthy controls investigated in previous studies, non-Cp Cu and Cu:Cp were higher in AD than healthy controls (both P < .001), but lower than in WD patients at baseline. While non-Cp Cu was similar in AD and WD, mean value of Cu:Cp distinguished AD from WD (P < .016), with the Cu:Cp Cohen d value of 0.8 (indicating a large biological effect) in AD vs healthy controls, which further increases in WD to 2.2. Concentrations of 24-hour urine copper in 35 healthy controls were compared with those at baseline of an AD patient group analyzed in a previous study on the effect of D-pen on the disease progression. AD patients at baseline had higher concentrations of 24-hour urine copper (P < .001; AD 12.05 mug/day [median, interquartile range 7.85-22.50]) than healthy controls (4.82 mug/day (median, interquartile range: 3.31-7.43]). Values of 24-hour urine copper higher than the cutoff of 200 mug/day were found in 87% of WD and 78% of AD. The direct comparison of AD and WD patients shows a copper failure affecting both diseases, but at a different degree, with the Cu:Cp signifying a more severe grade in WD.",adult;Alzheimer disease;congenital malformation;controlled study;disease exacerbation;drug therapy;female;human;human tissue;male;meta analysis;treatment failure;urine;Wilson disease;biological product;ceruloplasmin;copper;endogenous compound;conference abstract,"Rongioletti, M.;Squitti, R.;Ghidoni, R.;Ivanova, I.;Benussi, L.;Binetti, G.;Siotto, M.;Papa, F.",2018,January,http://dx.doi.org/10.1093/ajcp/aqx115.025,0,0,
3412,When medication is not the culprit: Abnormal liver function in a patient with polyarticular juvenile idiopathic arthritis,"Background: Hepatotoxicity is a well-recognised side-effect of diseasemodifying antirheumatic drugs (DMARD). In patients with juvenile idiopathic arthritis (JIA), transient elevation of transaminases is common in those receiving methotrexate and some anti-tumour necrosis factor alpha medications. There is little evidence to guide optimal monitoring, interpretation of results, further investigation or intervention. Aims: We present an 8-year old girl with polyarticular JIA and persistently raised liver enzymes during the first eighteen months of treatment, leading to further investigation and a consequent diagnosis of Wilson's disease. Methods: We produced a retrospective case review. Results: A diagnosis of JIA was made at 6 years. She received steroid injections to multiple joints and was commenced on methotrexate. Alanine aminotransferase (ALT) was marginally elevated at diagnosis (59 U/l, normal range <50), but normalised prior to commencing treatment. ALT levels rose shortly after starting methotrexate and remained elevated. Gamma-glutamyl transferase (GGT) was occasionally marginally raised, but other liver function remained normal. Over subsequent months, elevated ALT often coincided with upper respiratory tract infections. Methotrexate was omitted on a number of occasions due to ALT levels >4x upper limit of normal. The dose was reduced and extended to fortnightly, with improvement but not normalisation of ALT. Infliximab was commenced at eight months due to ongoing active JIA. Liver function remained abnormal (highest ALT 433 U/l) and at twelve months was associated with a new development of worsening abdominal pain and nausea. A decision was made to stop methotrexate and infliximab. Baseline investigations into other causes for continuing hepatitis and abdominal pain were normal. JIA disease control became increasingly difficult and she was commenced on adalimumab. She was discussed with gastroenterology colleagues eighteen months after diagnosis. Further investigations revealed low caeruloplasmin and an alpha-1 antitrypsin (A1AT) carrier phenotype. Repeat ultrasound scan showed mild liver inflammation and fatty infiltration. Serum copper level and urinary penicillamine challenge were highly suggestive of Wilson's disease. Liver biopsy demonstrated an elevated copper content and steatosis. Genetic testing remains outstanding. She was commenced on zinc acetate, with normalisation of liver function within weeks. Abatacept was chosen for ongoing JIA management, with reduced risk of associated liver upset which would interfere with Wilson's disease monitoring. Conclusions: Wilson's disease is rare and transaminase abnormalities vary considerably. Early diagnosis and management, before organ damage has occurred, will optimise outcome. As in this case, however, children are usually asymptomatic and abnormal transaminases noted fortuitously. Interpreting blood results of paediatric patients on methotrexate is challenging, with little evidence to guide intervention. In our case, there was no improvement in liver function with alterations in drug therapy, triggering further investigations for underlying pathology. The case illustrates the importance of consideration of other causes of raised liver transaminases during methotrexate monitoring, and highlights the value of early discussion with gastroenterology.",abdominal pain;adverse drug reaction;alanine aminotransferase level;case report;case study;child;clinical article;congenital malformation;copper blood level;diagnosis;disease control;drug combination;drug therapy;early diagnosis;female;gastroenterology;genetic screening;girl;hepatitis;human;human tissue;hypertransaminasemia;injection;joint;juvenile rheumatoid arthritis;liver biopsy;liver function;monitoring;nausea;organ injury;pathology;phenotype;retrospective study;school child;side effect;steatosis;ultrasound;upper respiratory tract infection;Wilson disease;abatacept;adalimumab;alanine aminotransferase;alpha 1 antitrypsin;ceruloplasmin;endogenous compound;gamma glutamyltransferase;infliximab;liver enzyme;methotrexate;penicillamine;steroid;zinc acetate;conference abstract,"Bertram, L.;Kelly, I.;Raimondo, V.;Brennan, M.;Henderson, P.;Davidson, J.",2017,October,,0,0,
3413,Wilson disease. [German],"Wilson disease is a rare hereditary disorder of copper metabolism. The genetic defect is caused by various mutations in the copper-transporting enzyme ATP7B, located mainly in the liver and brain. Clinical symptoms are highly variable, with any combination of hepatic and/or neurological or psychiatric manifestations. The age of onset varies from early childhood to young adults and can even be manifested in later ages. The clinical diagnosis is based on a combination of clinical, biochemical and molecular markers. Treatment using chelating agents and zinc salts is effective when started early or even better at presymptomatic stages of the disease. Copyright © 2018, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.",Central nervous system;Chelating agents;Copper toxicity;Liver;Wilson disease protein;article;human;onset age;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];chelating agent/dt [Drug Therapy];molecular marker;zinc derivative/dt [Drug Therapy],"Huster, D.",2018,01 Feb,http://dx.doi.org/10.1007/s00108-017-0378-x,0,0,1329
3414,"The early history of manganese and the recognition of its neurotoxicity, 1837-1936","The history of the biomedical recognition manganese-caused neurotoxicity mirrors changing technologies as much as it does the ontology of parkinsonism. The initial 1837 report of manganese-induced neurologic injury was made by John Couper, a university-based physician in Scotland. He made clear that the outbreak occurred among workers at the Charles Tennant bleach manufactory in the environs of Glasgow. The relatively new technology of chlorine generation using manganese accounted for the novel exposure involved. At the time, this factory was the largest hypochlorite bleaching powder producer in the world. As the 19th century progressed, technological change in steel fabrication requiring higher manganese content greatly increased demand for the metal. Nonetheless, more than six decades elapsed before the next reports of manganese neurotoxicity emerged. Two unrelated outbreaks (both on Continental Europe) were reported within weeks of each other in 1901, one by von Jaksch and the other by Embden. All the cases were heavily exposed to manganese-containing dust. By the eve of the First World War, a total of 9 patients with manganese-caused neurologic illness had been reported in five separate Continental European publications. Meanwhile, new technology led to another exposure source. Magnetic separation techniques allowed the extraction of zinc from mixed ore also containing iron and manganese, leading to exploitation of a unique source of high manganese-content ore found in New Jersey. Not long after that technology's introduction, in 1912 Casamajor reported the first U.S. cases of manganism, detailing classic findings. Additional cases from the same cohort were reported a few years later, with continued exposure driven by First World War-driven demand for manganese to be used in armaments. The nosology of chronic manganese neurotoxicity remained in flux, with considerable emphasis on shared attributes with Wilson's disease, a syndrome only then recently described. A landmark 1924 primate study by Mella showed manganese-induced basal ganglion damage; human autopsy study data in the years following further supported the view that manganese toxicity represented a parkinsonian syndrome. As the 1937 centenary of Couper's first report approached, newer technologies (electric arc welding and battery making) were being linked to manganese-caused disease, even as mineral extraction was expanding as a global source of exposure. Copyright © 2017",History;Lenticular degeneration;Manganese;Neurotoxicity;Nosology;Paralysis agitans;article;bleaching;brain damage;chemical industry;differential diagnosis;disease classification;disease severity;dust exposure;environmental exploitation;environmental exposure;epidemic;extraction;furnace;geography;human;intoxication;magnetic separation;metal industry;neurologic disease;nonhuman;occupational exposure;parkinsonism;physical chemistry;priority journal;symptom;technology;war;welding;Wilson disease;chlorine;iron;manganese/to [Drug Toxicity];zinc;manganese toxicity,"Blanc, P. D.",2018,January,http://dx.doi.org/10.1016/j.neuro.2017.04.006,0,0,4
3415,"Wilson's Disease in Children: A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition","Background: Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism, and molecular analysis of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims at removal of copper excess by chelating agents as D-penicillamine, trientine, or inhibition of intestinal copper absorption with zinc salts. Acute liver failure often requires liver transplantation. This publication aims to provide recommendations for diagnosis, treatment, and follow-up of WD in children. Methods: Questions addressing the diagnosis, treatment, and follow-up of WD in children were formulated by a core group of ESPGHAN members. A systematic literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to 2016 was performed focusing on prospective and retrospective studies in children. Quality of evidence was assessed according to the GRADE system. Expert opinion supported recommendations where the evidence was regarded as weak. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique. Copyright © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.",children;diagnosis;hepatitis;liver;treatment;Wilson's disease;abdominal pain/si [Side Effect];acute liver failure/pv [Special Situation for Pharmacovigilance];adolescent;adult;aphthous stomatitis/si [Side Effect];aplasia/si [Side Effect];arthralgia/si [Side Effect];article;bone marrow toxicity/si [Side Effect];ceruloplasmin blood level;child;child nutrition;childhood disease/di [Diagnosis];childhood disease/su [Surgery];consensus;copper metabolism;cutis laxa/si [Side Effect];diagnostic test;drug dose increase;drug efficacy;drug formulation;drug hypersensitivity/si [Side Effect];drug safety;drug substitution;drug withdrawal;elastosis/si [Side Effect];epigastric pain/si [Side Effect];European;eye disease;family study;fever/si [Side Effect];gene mutation;genetic counseling;hematuria/si [Side Effect];human;lichen planus/si [Side Effect];liver biopsy;liver disease/di [Diagnosis];liver disease/dt [Drug Therapy];liver disease/su [Surgery];liver function test;liver transplantation;lupus like syndrome/si [Side Effect];lymphadenopathy/si [Side Effect];medical society;nausea/si [Side Effect];neutropenia/si [Side Effect];patient compliance;patient monitoring;pediatrician;pemphigus/si [Side Effect];practice guideline;priority journal;proteinuria/si [Side Effect];rash/si [Side Effect];recommended drug dose;scoring system;screening test;sideroblastic anemia/si [Side Effect];slit lamp microscopy;stomach ulcer/si [Side Effect];symptom;systematic review;thrombocytopenia/si [Side Effect];treatment indication;urinary excretion;vomiting/si [Side Effect];Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/su [Surgery];young adult;ceruloplasmin/ec [Endogenous Compound];chelating agent/cb [Drug Combination];chelating agent/dt [Drug Therapy];copper;gluconate zinc/dt [Drug Therapy];gluconate zinc/pr [Pharmaceutics];gluconate zinc/pd [Pharmacology];penicillamine/ae [Adverse Drug Reaction];penicillamine/cm [Drug Comparison];penicillamine/do [Drug Dose];penicillamine/dt [Drug Therapy];penicillamine/pd [Pharmacology];trientine/ae [Adverse Drug Reaction];trientine/cm [Drug Comparison];trientine/do [Drug Dose];trientine/dt [Drug Therapy];trientine/pd [Pharmacology];Wilson disease protein;zinc acetate/dt [Drug Therapy];zinc acetate/pr [Pharmaceutics];zinc acetate/pd [Pharmacology];zinc derivative/ae [Adverse Drug Reaction];zinc derivative/cb [Drug Combination];zinc derivative/dt [Drug Therapy];zinc derivative/pr [Pharmaceutics];zinc derivative/pd [Pharmacology];zinc sulfate/ae [Adverse Drug Reaction];zinc sulfate/dt [Drug Therapy];zinc sulfate/pr [Pharmaceutics];zinc sulfate/pd [Pharmacology];Kayser Fleischer rings,"Socha, P.;Janczyk, W.;Dhawan, A.;Baumann, U.;D'Antiga, L.;Tanner, S.;Iorio, R.;Vajro, P.;Houwen, R.;Fischler, B.;Dezsofi, A.;Hadzic, N.;Hierro, L.;Jahnel, J.;McLin, V.;Nobili, V.;Smets, F.;Verkade, H. J.;Debray, D.",2018,01 Feb,http://dx.doi.org/10.1097/MPG.0000000000001787,0,0,
3416,Genotype and clinical course in 2 Chinese Han siblings with Wilson disease presenting with isolated disabling premature osteoarthritis,"Rationale: Premature osteoarthritis (POA) is a rare condition in Wilson disease (WD). Particularly, when POA is the only complaint of a WD patient for a long time, there would be misdiagnosis or missed diagnosis and then treatment delay. Patient concerns and diagnosis: Two Chinese Han siblings were diagnosed as WD by corneal K-F rings, laboratory test, and mutation analysis. They presented with isolated POA during the first 2 decades or more of their disease course, and were of missed diagnosis during that long time. The older affected sib became disabled due to his severe osteoarthritis when he was as young as 38 years old. Two compound heterozygous pathogenic variants c.2790-2792del and c.2621C>T were revealed in the ATP7B gene through targeted next-generation sequencing (NGS). Lessons: Adolescent-onset POA could be the only complaint of WD individual for at least 2 decades. Long delay in the treatment of WD's POA could lead to disability in early adulthood. Detailed physical examination, special biochemical test, and genotyping through targeted NGS should greatly reduce diagnosis delay in atypical WD patients with isolated POA phenotype. Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.",atp7b;Premature osteoarthritis;Wilson disease;adult;adulthood;arthralgia;article;biochemical analysis;case report;ceruloplasmin blood level;Chinese;clinical article;computer assisted tomography;consanguinity;delayed diagnosis;disease course;echography;endocrine disease;exon;gene mutation;genetic variability;genotype;heterozygote;human;laboratory test;male;metabolic disorder;neurologic examination;next generation sequencing;nuclear magnetic resonance imaging;osteoarthritis/di [Diagnosis];phenotype;physical examination;prematurity/di [Diagnosis];priority journal;rare disease;Sanger sequencing;sibling;slit lamp microscopy;ceruloplasmin/ec [Endogenous Compound];genomic DNA/ec [Endogenous Compound];penicillamine;trihexyphenidyl;premature osteoarthritis/di [Diagnosis],"Ye, S.;Dai, T.;Leng, B.;Tang, L.;Jin, L.;Cao, L.",2017,01 Nov,http://dx.doi.org/10.1097/MD.0000000000008641,0,0,
3417,Hyperacute neurological symptoms with bilateral symmetrical lesions in pons and basal ganglia in Wilson's disease,"Background: Wilson disease is a rare autosomal recessive inherited disorder of copper metabolism that is characterized by excessive deposition of copper in the liver, brain, and other tissues with neuropsychiatric features being a prominent part of the clinical picture. Objective Patients and Methods/Material and Methods: 43-year-old woman, with a 3 weeks history of rapidly progressive, severe ataxic gait, paraparesis, dysarthria was registered in our Neurology department. Clinical examination revealed marked anxiety, finger dystonia, bilateral pyramidal signs and clonus. Within two weeks the patient became bed ridden because of severe gait apraxia. Blood serum transaminases were normal, ceruloplasmin levels low and urine copper levels high. Brain MRI showed symmetrical T2/FLAIR hyperintense lesions in pons, thalamus and putamen with a second MRI, two weeks later, showed also bilateral involvement of caudate nucleus and being supportive of the clinical deterioration observed in the first two weeks after registration. Kayser-Fleischer rings were present on ophthalmologic examination. As abdominal computerized tomography showed normal liver structure, a liver fibroscan was performed showing progressive cirrhosis. Genetic studies showed Glu1064Ala mutation on ATP7B gene, compatible with Wilson disease. Penicillamine treatmentwas started with a slow, gradual improvement in the patient's neurological status. Results Conclusion: The neurological rapidly progressive ataxic gait and paraparesis as the cardinal neurological signs in this hyperacute case of Wilson's disease with symmetrical bilateral involvement of the basal ganglia and pons without involvement of other brain regions. (Figure Presented).",adult;aminotransferase blood level;anxiety;ataxic gait;brain region;case report;caudate nucleus;clinical assessment;clinical examination;clonus;computer assisted tomography;deterioration;dysarthria;dystonia;elastograph;female;gait apraxia;gene expression;gene mutation;human;human tissue;immobility;liver cirrhosis;liver structure;neurology;nuclear magnetic resonance imaging;ophthalmology;paraplegia;pons;putamen;pyramidal sign;registration;thalamus;urine;Wilson disease;ceruloplasmin;endogenous compound;penicillamine;Wilson disease protein,"Egbarya, A.;Sabetay, S.;River, Y.;Abu Raya, M.",2017,October,http://dx.doi.org/10.1016/j.jns.2017.08.724,0,0,
3418,Copper and zinc homeostasis: Lessons from Drosophila melanogaster,"Maintenance of metal homeostasis is crucial for many different enzymatic activities and in turn for cell function and survival. In addition, cells display detoxification and protective mechanisms against toxic accumulation of metals. Perturbation of any of these processes normally leads to cellular dysfunction and finally to cell death. In the last years, loss of metal regulation has been described as a common pathological feature in many human neurodegenerative diseases. However, in most cases, it is still a matter of debate whether such dyshomeostasis is a primary or a secondary downstream defect. In this review, we will summarize and critically evaluate the contribution of Drosophila to model human diseases that involve altered metabolism of metals or in which metal dyshomeostasis influence their pathobiology. As a prerequisite to use Drosophila as a model, we will recapitulate and describe the main features of core genes involved in copper and zinc metabolism that are conserved between mammals and flies. Drosophila presents some unique strengths to be at the forefront of neurobiological studies. The number of genetic tools, the possibility to easily test genetic interactions in vivo and the feasibility to perform unbiased genetic and pharmacological screens are some of the most prominent advantages of the fruitfly. In this work, we will pay special attention to the most important results reported in fly models to unveil the role of copper and zinc in cellular degeneration and their influence in the development and progression of human neurodegenerative pathologies such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Friedreich's Ataxia or Menkes, and Wilson's diseases. Finally, we show how these studies performed in the fly have allowed to give further insight into the influence of copper and zinc in the molecular and cellular causes and consequences underlying these diseases as well as the discovery of new therapeutic strategies, which had not yet been described in other model systems. Copyright © 2017 Navarro and Schneuwly.",Copper;dmtf-1;Drosophila melanogaster;Human diseases;In vivo modeling;Metal homeostasis;Methallothioneins;Zinc;Alzheimer disease;copper metabolism;detoxification;disorders of mitochondrial functions;endoplasmic reticulum;Friedreich ataxia;gene expression regulation;gene interaction;human;Huntington chorea;membrane transport;Menkes syndrome;metabolic regulation;nonhuman;Parkinson disease;phenotype;protein expression;protein protein interaction;review;single nucleotide polymorphism;Wilson disease;zinc homeostasis;zinc metabolism;amyloid beta protein/ec [Endogenous Compound];amyloid precursor protein/ec [Endogenous Compound];chaperone/ec [Endogenous Compound];Menkes protein/ec [Endogenous Compound];metallothionein I/ec [Endogenous Compound];metallothionein II/ec [Endogenous Compound];metallothionein III/ec [Endogenous Compound];superoxide dismutase/ec [Endogenous Compound];transcription factor/ec [Endogenous Compound];transferrin receptor/ec [Endogenous Compound];tyrosine 3 monooxygenase/ec [Endogenous Compound];unclassified drug;Wilson disease protein/ec [Endogenous Compound];metal regulatory transcription factor 1/ec [Endogenous Compound],"Navarro, J. A.;Schneuwly, S.",2017,21 Dec,http://dx.doi.org/10.3389/fgene.2017.00223,0,0,
3419,Wilson's disease in a cohort of pediatric patients in Slovakia. [Slovak],"Background: Wilson's disease (WD) is a rare, metabolic, genetically conditioned disease. Patients may be asymptomatic for varying periods of time orthe disease may present with non-specific symptoms up to organ-specific disability. Diagnosis of the disease is confirmed by an analysis of clinical signs and the results of targeted examinations. If diagnosed early, the disease is treatable, with chelation therapy as the principal approach. Patients with acute liver failure are indicated for liver transplantation. Material and Methods: The authors retrospectively evaluate a group of 17 patients with WD diagnosed in childhood or adolescence. Results: WD was confirmed in 17 patients aged between 3 and 18 years at the 1<sup>st</sup> Pediatric Department of the Faculty of Medicine and Children's University Hospital in Bratislava in the period from 2000 to 2015. The most common presentation of WD was in the liver (n = 13 patients; 77%). In two patients WD manifested with acute hepatic failure in adolescent age. Long-term increase in aminotransferase activity was detected in nine patients. In two patients we identified WD at the stage of cirrhosis. Neurological symptoms were observed in two patients. The most commonly confirmed genetic mutation in the Central European region, H1069Q, was confirmed in 6 homozygous carriers, while 10 patients were compound heterozygous carriers. In one patient, pathological mutation could not be confirmed even by extensive genetic testing. Three patients from the cohort of 17 children underwent liver transplantation, 2 asymptomatic children are treated with zinc, 11 patients are treated with penicillamine, and 1 patient with trientine dihydrochloride. Conclusion: WD is a rare childhood disease. Its most common manifestation is the hepatic form in the second decennium. Establishing the diagnosis may be very challenging. There is no single highly sensitive and specific parameter clearly pointing to the diagnosis. Serum ceruloplasmin level is the primary screening test. Plasma levels of copper and renal excretion of copper serve as auxiliary examinations. The gold standard for confirming the diagnosis is to determine copper concentrations in the liver in dried liver tissue. Genetic testing is of benefit when confirming the diagnosis of WD, particularly in first-degree relatives, asymptomatic individuals. Early diagnosis and treatment can prevent progression of the disease. If left untreated, the disease is fatal.",Copper in dried liver tissue;Copper-ceruloplasmin;Wilson's disease;acute liver failure/pv [Special Situation for Pharmacovigilance];adolescent;adult;article;Central European;child;clinical article;clinical feature;cohort analysis;enzyme activity;gene mutation;genetic screening;heterozygosity;homozygosity;human;liver cirrhosis;liver transplantation;neurologic disease;retrospective study;Slovakia;Wilson disease/dt [Drug Therapy];aminotransferase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy],"Kosnacova, J.;Podracka, L.",2017,,http://dx.doi.org/10.14735/amgh2017476,0,0,
3420,Hyperammonemic encephalopathy and new-onset seizures in a roux-en-y and short bowel syndrome patient,"Learning Objectives: Rare cases have been reported of hyperammonemia after Roux-en-Y gastric bypass (RYGB) and small bowel resection surgeries separately. Here, we discuss a patient with hyperammonemic encephalopathy secondary to RYGB surgery and small bowel resection, complicated by new-onset seizures. Methods: A 45-year-old woman who had RYGB surgery 15 years ago and small bowel resection 5 years prior presented with decreased oral intake, weakness, and altered mental status (AMS). She had a 7-month history of frequent admissions for elevated ammonia levels and AMS, previously treated with rifaximin and lactulose. She was intubated for airway protection. On admission to our ICU, she was found to have an elevated ammonia level of 140 mcg/dL (15-45 mcg/dL) after already receiving rifaximin and lactulose for 4 days. Transaminase levels were normal. Prior liver biopsy was noted to be negative for cirrhosis, but showed fatty liver changes. A previous work-up for Wilson's Disease was negative. These results increased suspicion for a urea cycle disorder. Serum amino acid levels and urine orotic acid were tested, revealing elevated urine orotic acid at 2.4 mmol/mol Cr (0.4-1.2) and low serum citrulline at 9 nmol/mL (17-46), arginine at 24 nmol/ mL (32-120), and ornithine at 21 nmol/mL (38-130), indicative of a partial ornithine transcarbamylase (OTC) deficiency. Following treatment with lactulose, rifaximin, and a low protein parenteral diet, ammonia levels normalized by hospital day (HD) 8. Mental status improved and she was extubated and downgraded to the hospital floors. On HD10, she was readmitted to the ICU after new-onset tonic-clonic seizures, which resolved with Ativan. Micronutrient deficiency was suspected as the cause. Serum electrolyte levels were not consistent with refeeding syndrome. Serum lab values displayed low levels of zinc, selenium, and vitamin B6. She was placed on phenytoin, lamotrigine, and clozabam. With supplementation of these micronutrients, she has remained seizure free. Results: Although rare, partial OTC deficiency may cause severe complications following RYGB and small bowel resection surgeries, even years after the procedures. Careful dietary formulation as well as replacement of micronutrients due to malabsorptive state is essential in the treatment of these patients.",adult;airway;amino acid blood level;case report;complication;diet;drug combination;drug therapy;electrolyte blood level;fatty liver;female;gene expression;human;human tissue;hyperammonemia;liver biopsy;liver cirrhosis;mental health;middle aged;ornithine transcarbamylase deficiency;parenteral nutrition;refeeding syndrome;roux en y gastric bypass;short bowel syndrome;small intestine resection;surgery;tonic clonic seizure;urine;weakness;Wilson disease;aminotransferase;ammonia;arginine;chromium;citrulline;endogenous compound;lactulose;lamotrigine;lorazepam;ornithine;orotic acid;phenytoin;pyridoxine;rifaximin;selenium;trace element;zinc,"Grogg, J.;Feinman, J.;El Husseini, I.;Hussain, S.",2018,January,http://dx.doi.org/10.1097/01.ccm.0000528446.22292.0d,0,0,
3421,"Dried matrix spots and clinical elemental analysis. Current status, difficulties, and opportunities","This article examines the increasing importance of dried matrix spots (DMS), such as dried blood spots, dried urine spots, etc., in biomedical research, the challenges associated with their analysis when quantitative elemental information is aimed at, as well as the benefits deriving from the further usage of these types of samples. The article briefly reviews the historical evolution of this sampling approach in elemental clinical analysis, stressing prospective areas of applications (e.g., newborns or prosthesis control), the methodologies most recently developed to produce DMS of known volume, as well as novel strategies proposed to analyze them, often related to direct solid sampling techniques or fast lixiviation methods. Finally, the article discusses the type of information that could be obtained after isotopic analysis of DMS when targeting non-traditional stable isotopes (e.g., Cu, Fe or Zn), which can significantly help in the early diagnosis of some medical conditions (e.g. Wilson's disease). Copyright © 2017 Elsevier B.V.",Dried blood spots;Dried matrix spots;Dried urine spots;Isotopic analysis;Solid sampling;Trace elemental analysis;analytic method;atomic absorption spectrometry;blood sampling;body fluid;chemical analysis;contamination;dried blood spot testing;elemental analysis;health program;human;isotope analysis;lead blood level;mass spectrometry;newborn screening;priority journal;review;sampling;storage;traffic and transport;volumetry;welfare;copper;iron;lead;mercury;analytical equipment;filter;delves cup;dried matrix spot;filter paper,"Resano, M.;Belarra, M. A.;Garcia-Ruiz, E.;Aramendia, M.;Rello, L.",2018,February,http://dx.doi.org/10.1016/j.trac.2017.12.004,0,0,
3422,[52] Follow-up of liver steatosis and fibrosis in children with Wilson's disease using transient elastography (Fibroscan),"Introduction: Liver damage in Wilson's disease ranges from simple steatosis, steatohepatitis to severe fbrosis. Transient elastography (Fibroscan Echosens) has been applied in many chronic liver diseases for non-invasive assessment of liver stifness/fbrosis and steatosis. We aimed to evaluate the change of liver stif-ness/fbrosis and steatosis and liver function over time in children with Wilson's disease using Fibroscan. Material and methods: We included 33 children with mean age of 11.5 yrs with Wilson's disease, treated with either zinc or d-penicillamine. At the baseline and afer a mean period of 1.5 yrs all patients underwent Fibroscan examinations with medium (M) probe to assess liver stifness (E) and steatosis (Controlled Attenuation Parameter, CAP). Repeated laboratory liver function tests were performed at the same time. Results: At baseline, our patients presented with slightly elevated liver enzymes ALT-49.5 U/I (27.5-69), AST-34.5 U/I (25.5-45.5), GGTP-26 U/I (19.5-35.5) and well preserved liver function INR-1.1 (1.05-1.16) [median, lower, upper quartile]. Initial Fibros-can examination showed normal median liver stifness 4.4 kPa (M probe) (4.0-5.4) and slightly elevated liver steatosis CAP-257 dB/m (235-283) [median, lower, upper quartile]. Afer a period of 1.5 years we found decrease, but not statistically signifcant, in ALT, AST and INR in our patients. Only GGTP was signifcantly lower than the baseline results (p = 0.02). Similarly we have not observed marked diference in liver steatosis (CAP) or liver stifness by Fibroscan when compared baseline and repeated measurements. Conclusion: Liver stifness/fbrosis and steatosis seem not to signifcantly improve in the short-term follow-up observation period of children with Wilson's disease, as based on the Fibroscan measurements. Transient elastography (Fibroscan) can be easily used in children with Wilson's disease for monitoring of liver stifness/fbrosis and steatosis.",attenuation;child;elastograph;fatty liver;female;fibrosis;follow up;human;hypertransaminasemia;international normalized ratio;liver function test;major clinical study;male;monitoring;transient elastography;Wilson disease;endogenous compound;gamma glutamyltransferase;penicillamine;zinc,"Janczyk, W.;Dadalski, M.;Socha, P.",2017,,,0,0,
3423,"[45] LiverMultiScan-new non-invasive method of assessment liver inflammation, steatosis and fibrosis-preliminary report","Introduction: Liver biopsy (LB) is an invasive procedure used for diagnose and treatment monitoring of liver diseases. We present preliminary experience with a new non-invasive method LiverMultiScan (LMS) assessing hepatic fbrosis, steatosis and infammation. Material and methods: Two children with autoimmune hepatitis (AIH) and one with Wilson disease have been performed a diagnostic or control liver biopsy (LB) and LMS. We compared grade of liver fbrosis, infammation and steatosis (based on LB) to LIF-score (based on multiparametric NMR, measurements of fat and iron liver content). LMS analysis was performed also in one healthy child (as a control). Results: In a 12-year-old male (recently diagnosed as AIH, not receiving therapy) LB revealed 3<sup>rd</sup> grade of fbrosis and 3<sup>rd</sup> grade of portal and lobular infam-mation. LMS analysis reports corresponds closely with this fndings: fat 0.7%, iron 0.9 mg/g, LIF-score 3.08%. In a 16 year-old female with AIH (on Azathioprine) The biopsy showed: fbrosis 1c, portal (2<sup>nd</sup> grade) and lobular (1<sup>st</sup> grade) infammation. In LMS: fat 3.2%, iron 0.8 mg/g, LIF-score 1.97%. In a 7.5-year-old female with Wilson disease (on Zincteral) in LB: steatosis 3<sup>rd</sup> grade, ballooning 2<sup>nd</sup> grade, fbrosis 2<sup>nd</sup> grade, portal and lobular infammation 1<sup>st</sup> grade. In LMS: fat 32.6%, iron 1.4 mg/g, LIF-score 3.08%. LMS analysis in a 17 year-old healthy girl without liver disease revealed: fat 1.2%, iron 1.2 mg/g, LIF-score 1.73%. According to the experience in adults LIF-score < 2% seems to be normal, and higher levels correlate with fbrosis and infammation. Conclusions: LIF-score corresponds closely to the grade of fbrosis and infammation on liver biopsy, and liver steatosis described by NMR is confrmed also by liver histopathology. LiverMultiScan is a new promis-ing non-invasive method that may be used for monitoring of liver diseases in children. Larger cohorts are needed to confrm and further delineate these fndings.",adolescent;adult;autoimmune hepatitis;case report;child;controlled study;diagnosis;fatty liver;female;fibrosis;girl;histopathology;human;human tissue;liver biopsy;male;monitoring;non invasive procedure;nuclear magnetic resonance;school child;Wilson disease;azathioprine;endogenous compound;iron;leukemia inhibitory factor;zinc sulfate,"Banerjee, R.;Janowski, K.;Wozniak, M.;Janczyk, W.;Chelstowska, S.;Jurkiewicz, E.;Grajkowska, W.;Pronicki, M.;Socha, P.",2017,,,0,0,
3424,Quantitative transcranial sonography in Wilson's disease and healthy controls: Cut-off values and functional correlates,"To compare transcranial sonography (TCS) findings in patients with predominantly neurological Wilson's disease (WD) to those from controls, and to correlate TCS data with the clinical profile of WD. Patients with WD (n = 40/f = 18) and healthy, matched controls (n = 49/f = 20) were assessed in terms of TCS, serum copper and iron parameters, and clinical scales, such as the Unified Wilson's Disease Rating Scale (UWDRS), Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini Mental State Examination (MMSE), and Beck Depression Inventory. Lenticular nuclei and substantia nigra echogenic area cut-off values clearly differentiated WD patients from controls (area under the curve: 95.4% and 79.4%). Substantia nigra echogenic area was significantly larger in male than in female patients (p = 0.001). Compared with controls, patients showed hyperechogenicity also in thalami and midbrain tegmentum/tectum; third ventricle width was increased and midbrain axial area was reduced. In the WD group, male gender correlated with substantia nigra echogenic area (r = 0.515, p = 0.0007) and serum ferritin levels (r = 0.479, p = 0.002); lenticular nuclei hyperechogenicity correlated with dystonia (r = 0.326, p = 0.04) and dysarthria (r = 0.334, p = 0.035); third ventricle width correlated with dystonia (r = 0.439 p = 0.005), dysarthria (r = 0.449, p = 0.004), parkinsonism (r = 0.527, p < 0.001), UWDRS neurological and total scores (both r = 0.504, p = 0.0009), MMSE (r = - 0.496, p = 0.001), and ACE-R (r = - 0.534, p = 0.0004). Lenticular nuclei echogenic area allowed highly accurate discrimination between patients and controls. The gender differences in substantia nigra echogenicity and iron metabolism are of interest in further studies in WD. TCS reflects different dimensions of WD pathology clearly differentiable from healthy controls and correlating with various clinical characteristics of WD. Copyright © 2017 Elsevier B.V.",Ferritin;Gender differences;Hyperechogenicity;Lenticular nucleus;Transcranial sonography;Wilson's disease;adolescent;adult;area under the curve;article;basal ganglion;Beck Depression Inventory;brain third ventricle;clinical assessment;cognition assessment;cohort analysis;comparative study;controlled study;copper blood level;dysarthria;dystonia;echography;female;ferritin blood level;human;iron metabolism;major clinical study;male;mesencephalon;Mini Mental State Examination;neurologic disease assessment;parkinsonism;priority journal;quantitative analysis;rating scale;sex difference;substantia nigra;tectum;tegmentum;Wilson disease;antidepressant agent;benzodiazepine derivative;ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];ferritin/ec [Endogenous Compound];iron/ec [Endogenous Compound];neuroleptic agent;penicillamine;transferrin/ec [Endogenous Compound];trientine;zinc derivative;Addenbrooke Cognitive Examination;Unified Wilson Disease Rating Scale,"Tribl, G. G.;Trindade, M. C.;Almeida, K. J.;Alves, R. C.;de Andrade, D. C.;Fonoff, E. T.;Machado, A. A.;Teixeira, M. J.;Barbosa, E. R.;Bor-Seng-Shu, E.",2018,15 Feb,http://dx.doi.org/10.1016/j.jns.2017.11.026,0,0,
3425,"Epidemiology, diagnosis, and treatment of Wilson's disease","Wilson's disease (WD) is an autosomal recessive disease caused by a mutation of the ATP7B gene, resulting in abnormal copper metabolism. The major clinical features of WD include liver disease, neurological disorders, K-F rings, and osteoporosis. The prevalence of WD in China is higher than that in Western countries. Early diagnosis and lifelong treatment will lead to better outcomes. Drugs such as sodium dimercaptosuccinate (Na-DMPS), Zn, and Gandou Decoction can be used to treat WD. Some studies have shown that the combination of traditional Chinese medicine and Western medicine is the best approach to treating WD. In order to identify better treatments, this article describes the specific clinical symptoms of Wilson's disease, its diagnosis, and treatment options.",d-pca;Kayser-Fleischer rings;Wilson's disease;Asia;cell transplantation;Chinese medicine;clinical feature;cornea disease;diagnostic imaging;disease association;genetic analysis;genetic counseling;hemodialysis;human;liver transplantation;molecular diagnosis;nerve injury;neurologic disease;osteoporosis;review;splenectomy;symptom;Western Hemisphere;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];Wilson disease/ep [Epidemiology];Wilson disease/et [Etiology];Wilson disease/pv [Special Situation for Pharmacovigilance];Wilson disease/su [Surgery];Chinese drug/dt [Drug Therapy];penicillamine/dt [Drug Therapy];succimer/dt [Drug Therapy];tetrathiomolybdic acid/dt [Drug Therapy];trientine/dt [Drug Therapy];zinc/dt [Drug Therapy];kayser fleischer ring,"Liu, J.;Luan, J.;Zhou, X.;Cui, Y.;Han, J.",2017,,http://dx.doi.org/10.5582/irdr.2017.01057,0,0,
3426,First case of cross-auxiliary double domino donor liver transplantation,"We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy (FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the firststage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava (IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-yearold female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver (left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and ""the left portal vein"" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children. Copyright © The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.",Case report;Domino liver transplantation;Double graft;Familial amyloid polyneuropathy;Ornithine transcarbamylase deficiency;Wilson's disease;abdominal distension;abnormal sensation;adult;anemia;article;blood chemistry;Chinese medicine;clinical article;computer assisted tomography;contrast enhancement;deterioration;digestive system function disorder;digestive system hemorrhage;drug hypersensitivity;echocardiography;familial amyloid polyneuropathy/di [Diagnosis];familial amyloid polyneuropathy/pv [Special Situation for Pharmacovigilance];female;follow up;heart failure/co [Complication];heart left ventricle ejection fraction;hematemesis/co [Complication];human;immunohistochemistry;liver dysfunction;liver graft;liver graft rejection/dt [Drug Therapy];liver graft rejection/pc [Prevention];liver transplantation;liver weight;living donor;lower limb;malnutrition;operation duration;rectum hemorrhage/co [Complication];methylprednisolone/dt [Drug Therapy];mycophenolate mofetil/dt [Drug Therapy];penicillamine;prealbumin/ec [Endogenous Compound];tacrolimus/dt [Drug Therapy];technetium 99m;double domino donor;Ttr gene,"Zhu, Z. J.;Wei, L.;Qu, W.;Sun, L. Y.;Liu, Y.;Zeng, Z. G.;Zhang, L.;He, E. H.;Zhang, H. M.;Jia, J. D.;Zhang, Z. T.",2017,28 Nov,http://dx.doi.org/10.3748/wjg.v23.i44.7939,0,0,
3427,Zeb2: Inhibiting the inhibitors in Schwann cells,"Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors. Zeb2 belongs to a family of highly conserved 2-handed zincfinger proteins and represses gene transcription by binding to E-box sequences in the regulatory region of target genes. The protein is known to repress E-cadherin during epithelial to mesenchymal transition (EMT) in tumor malignancy and mediates its functions by interacting with multiple co-factors. During nervous system development, Zeb2 is expressed in neural crest cells, the precursors of Schwann cells, the myelinating glial cells of peripheral nerves. Schwann cells lacking Zeb2 fail to fully differentiate and are unable to sort and myelinate peripheral nerve axons. The maturation inhibitors Sox2, Ednrb and Hey2 emerge as targets for Zeb2-mediated transcriptional repression and show persistent aberrant expression in Zeb2-deficient Schwann cells. While dispensible for adult Schwann cells, re-activation of Zeb2 is essential after nerve injury to allow remyelination and functional recovery. In summary, Zeb2 emerges as an ""inhibitor of inhibitors,"" a novel concept in Schwann cell development and nerve repair. Copyright © 2017 Taylor & Francis.",pns;Regeneration;Schwann cell;Schwann cell development;Transcription factor;cell maturation;cell proliferation;demyelination;down regulation;epigenetics;epithelial mesenchymal transition;genetic transcription;Hirschsprung disease;human;lipogenesis;mental deficiency;missense mutation;myelination;nerve compression;nervous system development;nonhuman;note;nuclear reprogramming;organogenesis;peripheral nervous system;priority journal;signal transduction;steady state;upregulation;Waardenburg syndrome;Wilson disease;endothelin 1/ec [Endogenous Compound];endothelin 2/ec [Endogenous Compound];endothelin 3/ec [Endogenous Compound];fatty acid binding protein 7/ec [Endogenous Compound];G protein coupled receptor/ec [Endogenous Compound];histone deacetylase 1/ec [Endogenous Compound];histone deacetylase 2/ec [Endogenous Compound];Notch receptor/ec [Endogenous Compound];octamer transcription factor 6/ec [Endogenous Compound];protein c jun/ec [Endogenous Compound];transcription factor/ec [Endogenous Compound];transcription factor PAX3/ec [Endogenous Compound];transcription factor Sox10/ec [Endogenous Compound];transforming growth factor beta/ec [Endogenous Compound];unclassified drug;transcription factor zeb2/ec [Endogenous Compound],"Brinkmann, B. G.;Quintes, S.",2017,01 Jan,http://dx.doi.org/10.1080/23262133.2016.1271495,0,0,
3428,Wilson's disease presenting as central pontine myelinolysis,,anarthria;aspiration pneumonia;case report;central pontine myelinolysis;ceruloplasmin blood level;clinical article;dysphagia;fatality;female;human;letter;nuclear magnetic resonance imaging;quadriplegia;sepsis;symptom;urine level;Wilson disease/di [Diagnosis];alanine aminotransferase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];penicillamine;zinc sulfate;kayser fleischer ring,"Safdarian, M.;Munhoz, R. P.;Aghaei, M.;Rohani, M.",2017,01 Dec,http://dx.doi.org/10.1007/s10072-017-3064-9,0,0,
3429,Managing pre-symptomatic Wilson disease in genetic era - More questions than answers,,article;Asian;aspartate aminotransferase blood level;asymptomatic disease;bilirubin blood level;case report;ceruloplasmin blood level;child;chronic hepatitis;clinical article;disease severity;follow up;gamma glutamyl transferase blood level;gene mutation;genetic screening;heterozygote;histopathology;human;international normalized ratio;liver biopsy;liver fibrosis;liver level;male;preschool child;prognostic assessment;Sanger sequencing;single nucleotide polymorphism;steatosis;Wilson disease/di [Diagnosis];Wilson disease/dt [Drug Therapy];aspartate aminotransferase/ec [Endogenous Compound];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];gamma glutamyltransferase/ec [Endogenous Compound];penicillamine/dt [Drug Therapy];Wilson disease protein/ec [Endogenous Compound];Atp7b gene;copper liver level,"Hadzic, N.;Deheragoda, M.;Dhawan, A.",2017,December,http://dx.doi.org/10.1016/j.clinre.2017.02.002,0,0,
3430,Case 2-2017: An 18-year-old woman with acute liver failure,,abdominal discomfort;abdominal distension;abdominal tenderness;acute liver failure/dt [Drug Therapy];adult;article;bronchitis/dt [Drug Therapy];case report;chelation therapy;confusion;coughing;diarrhea;differential diagnosis;dizziness;Doppler ultrasonography;dyspnea;erythrocyte concentrate;faintness;fatigue;female;fulminant hepatic failure/di [Diagnosis];human;human tissue;hyperammonemia;hyperbilirubinemia;hypotension;intensive care;international normalized ratio;jaundice;liver transplantation;nausea;nystagmus;premature labor;rhinorrhea;sinus tachycardia;solutio placentae;sore throat;splenomegaly;vagina bleeding;vomiting;wheezing;Wilson disease/di [Diagnosis];Wilson disease/pv [Special Situation for Pharmacovigilance];young adult;acetylcysteine/cb [Drug Combination];acetylcysteine/dt [Drug Therapy];alkaline phosphatase/ec [Endogenous Compound];aspartate aminotransferase/ec [Endogenous Compound];azithromycin/cb [Drug Combination];azithromycin/dt [Drug Therapy];azithromycin/vi [Intravitreal Drug Administration];bilirubin/ec [Endogenous Compound];ceruloplasmin/ec [Endogenous Compound];copper/ec [Endogenous Compound];dextromethorphan plus promethazine/cb [Drug Combination];dextromethorphan plus promethazine/dt [Drug Therapy];gamma glutamyltransferase/ec [Endogenous Compound];infusion fluid;morphine/cb [Drug Combination];ondansetron/cb [Drug Combination];penicillamine;piperacillin plus tazobactam/cb [Drug Combination];salbutamol/cb [Drug Combination],"Olson, K. R.;Davarpanah, A. H.;Schaefer, E. A.;Elias, N.;Misdraji, J.",2017,19 Jan,http://dx.doi.org/10.1056/NEJMcpc1613467,0,0,
3431,Clinical profile of patientswith simultaneous presentation of wilson's disease and autoimmune liver disease in a rural tertiary care centre,"Background andAim: The coexistence ofWilson's dis ease and autoimmune liver disease in a same patients is a rare entity. In this situation, combined treatment with steroid and D-Penicillamine may be effective. Methods:We analysed clinical, histological, laboratory profile for patients with chronic liver disease with aim of finding the etiology of the disease after ruling out common causes like alcohol, viruses and drugs. Results: Out of 10 patients 6 were males and 4 were females. Commonest clinical presentation was abdominal distension (80%), abdominal pain (30%), pedal edema (60%), splenomegaly (40%) and upper GI bleed (40%). Laboratory investigation revealed anemia (50%), throm bocytopenia (70%), prothrombin time prolongation in (60%), normal liver function in 60%, abnormal liver function in (40%). Hepatitis A, B, C and E were negative in all the cases. Serum cereloplasmin <20mg% in (30%), normal level in (70%). 24h urinary copper level range of >200 in (40%), 100 to 200 in (40%) and 90 to 100 in (20%). Autoimmune markers revealed ANA strong positivity in (40%), mild positivity in (60%). AMA, ASMA, Anti-LKM-1 were negative in all cases (100%). Liver biopsy showed features of Autoimmune liver disease and PERIPORTAL copper deposition in 80% of cases where 20% showed features of copper deposition in liver. Conclusion: The coexistence of Wilson's disease and autoimmune liver disease is a rare entity and clinician should have high level of suspicion in diagnosing the problem and medical treatment with steroids and D Pencillamine simultaneously to be started in these patients (Figure 1). (Figure Presented).",abdominal distension;abdominal pain;adult;anemia;autoimmune liver disease;chronic liver disease;clinical article;diagnosis;drug therapy;female;foot edema;gastrointestinal hemorrhage;hepatitis A;human;human tissue;liver biopsy;liver dysfunction;liver function;male;prothrombin time;splenomegaly;tertiary care center;Wilson disease;alcohol;steroid;unclassified drug,"Ramasubramanian, R.;Jaipaul, Y.;Shafique, A.;Rejoice, P.",2017,July,http://dx.doi.org/10.1016/j.jceh.2017.05.160,0,0,
3432,Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting,"Background and Aim: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. The study was done to evaluate the efficacy of penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. Methods: We retrospectively analysed case records of 31 symptomatic hepatic WD patients in whom disease severity scores (Child's, MELD, Nazer's and New Wilson Index score) and 24-h Urinary copper were compared at 3 time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow-up. Results: Of the 31 patients with symptomatic hepatic WDstudied, 10 had associated neuro-psychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (in 28 patients) or due to adverse effects of penicillamine (in 3). Child's grade was A in 6 patients, B in 5 and C in 17 at presentation (baseline). Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, median (range) and of subsequent zinc therapy was 363 (35-728) weeks. There was significant improvement in liver function tests and disease severity scores (Nazer's, New Wilson Index, Child's and MELD score) at transition from penicillamine to zinc compared to baseline. This improvement was maintained till end of study period. 17 patients with Child C cirrhosis at presentation were treated with penicillamine for 111 (2-320) weeks followed by zinc for 344 (41-652) weeks, ofwhom15 had significant improvement in liver function and disease severity scores until end of follow-up. 3 of 31 study patients died at 284, 112 and 437 weeks.Nopatient underwent liver transplantation. Conclusions: Penicillamine followed by zinc maybe safe and effective treatment in resource constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Our data also suggests that some patients with decompensated cirrhosis due to Wilson's disease may be managed with medical treatment, avoiding liver transplantation.",adverse drug reaction;chelation therapy;child;clinical article;clinical trial;controlled clinical trial;controlled study;decompensated liver cirrhosis;drug therapy;female;follow up;human;information processing;liver function test;liver transplantation;male;mental disease;Model For End Stage Liver Disease Score;retrospective study;side effect;Wilson disease;penicillamine;zinc;zinc sulfate,"Gupta, P.;Choksi, M.;Goel, A.;Zachariah, U.;Sajith, K. G.;Ramachandran, J.;Chandy, G.;Kurian, G.;Eapen, C. E.",2017,July,http://dx.doi.org/10.1016/j.jceh.2017.05.094,0,1,1140
3433,Pediatric hepatic wilson's disease: Experience from a tertiary care center,"Background and Aim: As there is paucity of exclu- sive literature on pediatric hepatic Wilson's disease (WD), this study was aimed to evaluate clinical presentation and outcome of children with hepatic WD. Methods: WD children satisfying >=2 of 3 crite- ria (serum ceruloplasmin <20mg/dL, positive Kayser- Fleischer ring, 24h urine copper>40mug)+/-liver histology managed in our department from January 2007 to June were analysed. Patients with >=9 months of ade- quate follow-up were evaluated for response to chelation therapy. They were analysed as following categories: (a) complete improvement (asymptomatic+normalization of transaminases, serum albumin and coagulation); (b) partial improvement (asymptomatic+near normalization of transaminases+serum albumin or cogulation); (c) progression (deterioration of synthetic functions, decom- pensation or death); (d) drug toxicity Results: 111 WD children aged 108 (36-180) months had an overall PELD score 16 (-11 to 60). Liver histology was consistent withWDin 68% (n=27/40). Figure 1 shows the presentation and outcome. Chelation was started in 84% (n=94). 14% (n=16) patients died in hospital due to advanced disease. 66 with follow up of 43 (9-144) months were analysed for outcome. 92% (n=60) were on D- penicillamine monotherapy and 6% (n=4) with additional severe neurological presentation were on D-penicillamine and zinc. Among those on D-penicillamine monotherapy, favourable outcome was seen in 58% (n=35). 13% (n=8) had drug toxicity and 12% (n=7) required addition of zinc due to disease progression. 6% (n=4) were started on tri entine. Overall favourable outcome was observed in 70% (n=46). Conclusions:This is the first and largest pediatric expe rience of hepatic WD. Majority of the hepatic WD can be managed on D-penicillamine monotherapy. Addition or change of chelation is required in select situations of drug toxicity and neurological presentation (Figure Presented).",adverse drug reaction;aged;ceruloplasmin blood level;chelation therapy;child;death;deterioration;female;follow up;human;human tissue;liver histology;major clinical study;male;monotherapy;remission;side effect;tertiary care center;toxicity;urine;very elderly;Wilson disease;aminotransferase;endogenous compound;penicillamine;serum albumin;zinc,"Das, M. C.;Sarma, M. S.;Yachha, S. K.;Srivastava, A.;Poddar, U.",2017,July,http://dx.doi.org/10.1016/j.jceh.2017.05.202,0,0,
3434,Spectrumof pediatricwilson disease froma non-transplant tertiary care center in North India,"Background and Aim: Wilson disease is a rare disor der of copper metabolism. There is a scarcity of reported series on this disorder in the pediatric age group.The study was done to evaluate the spectrum of Wilson disease in children managed in our institute. Methods: Retrospective analysis of 107 children diagnosed as Wilson disease over 10-year period was con ducted. Results:The symptomswere jaundice in 56.07%, ascites in 45.7%, encephalopathy in 10.2%, bleeding in 29%, neurologicalmanifestation in 21.4% and psychiatricman ifestation in 4.6% patients. Consanguinity was present in 14% whereas family history of Wilson disease could be traced in 41.1% patients. Examination showed hepato megaly in 82.2%, splenomegaly in 64.4%, and ascites in 37.3% patients. Presentationwas hepatic in 81.3% and hep atolenticular in 18.6%. Other causes of liver disease like hepatitis A, E, B, C, AIH, PSC, overlap were excluded. KF rings were present in 72.4% of hepatic Wilson and 90% of hepatolenticular Wilsonians. Familial Wilson disease was present in 12%. Serum Ceruloplamin was low in 93% of hepatic and 95% of hepatolenticular Wilson. 67.2% of themhad value<10mg/dl.Urine copper was performed in 90 patients with 73.3% having value>100mug/24h. Liver biopsy was possible only in 50% patients. MRI brain changes were seen in all neurowilson patients. Types of hepatic presentation were cirrhosis with portal hyperten sion in 46.3%, chronic liver disease in 7.2%, ACLF in 13.4%, acute liver failure in 2%, acute hepatitis in 18.5% and asymptomatic in 13.4% patients.4 patients were enlisted for transplantation, 3 were successful and 1 died. All patients with hepatic manifestations were started on D penicillamine whereas patients with neurowilson were started on Zinc followed by slow administration of D penicillamine and are being followed. Conclusion: 80% of children had hepatic disease (low ceruloplasmin: 93%, KFR: 72%) whereas 20% had hepato lenticular manifestations (low ceruloplasmin: 95%, KFR: 90%). The hepatic manifestations were cirrhosis, acute hepatitis, ACLF, ALF and asymptomatic hepatomegaly.",acute hepatitis;acute on chronic liver failure;ascites;bleeding;brain disease;child;consanguinity;diagnosis;drug therapy;family history;female;hepatitis A;hepatomegaly;human;human tissue;India;jaundice;liver biopsy;liver cirrhosis;major clinical study;male;nuclear magnetic resonance imaging;retrospective study;splenomegaly;tertiary care center;transplantation;urine;Wilson disease;ceruloplasmin;endogenous compound;penicillamine;zinc,"Menon, J.;Thapa, B. R.;Srikanth, K. P.;Sharma, S.;Lal, S.",2017,July,http://dx.doi.org/10.1016/j.jceh.2017.05.172,0,0,
3435,Wilsonian fulminant hepatic failure in children and adolescents: A systematic review of 274 cases,"Background: Wilsonian Fulminant Hepatic Failure (WFHF) is a serious condition, typically requiring liver transplantation (LT). As a result of its relative rarity, WFHF has been diffcult to study in depth. Data in pediatric populations (<18 years of age) are scarce and limited to case reports and small case series. The aims of this systematic review were to examine the clinical and biochemical characteristics, treatment and outcomes of children and adolescents with WFHF. Methods: Database searches were conducted in PubMed, Web of Science, and Google Scholar. The search was restricted to papers published in English, between January-1984 and March 01<sup>st</sup>, 2017. Papers were excluded if pediatric data were not extractable. Wilson disease (WD) was defned as per AASLD guidelines. Due to the heterogeneity of the defnition of acute liver failure (ALF) in the literature, subjects were included if they were defned as having ALF by the paper's authors. The following data points were extracted from articles: study design, initial clinical and biochemical characteristics, genetic mutations, treatment and clinical outcome. If not reported, the following ratios were calculated: alkaline phosphatase (ALP) to total bilirubin (TBIL) < 2 and aspartate aminotransferase (AST) to alanine aminotransferase (ALT) > 4. Results: A total of 56 (case reports (30), case-series (23) and cohort studies (3)) manuscripts involving 274 participants met the study inclusion criteria. The majority of studies were conducted in Asia (21) followed by 19 in North America, 15 in Europe, and 1 in Australia. Studies ranged in size from 1-61 subjects with a median age of 12.9 years at presentation (range 4.0-17.6 years). Females represented 74% (202/274) of all patients. Kayser-Fleischer rings were seen in 80% (153/191) and Coombs negative hemolytic anemia was reported in 98% (61/62). ALP/TBIL and AST/ALT ratios were evaluated in 60 (22%) and 63 (23%) of participants, respectively and were found to be < 2 and > 4 in less than 55% of subjects. 47% (128/274) of reported subjects underwent LT. Of these 58% (74/128) underwent deceased-donor LT, and 20% (25/128) received a live-donor LT. Graft type was not reported in the remaining subjects. 24% (65/274) of reported cases achieved spontaneous liver recovery with the assistance of extracorporeal liver support systems. Plasmapheresis was the most commonly used extracorporeal system and D-penicillamine was the most commonly used chelating agent in subjects who survived with their native liver. ATP7B mutations were only reported in 21 participants, thus limiting assessment of genotype-phenotype relationships. Conclusion: This is the frst systematic review examining WFHF in a substantial cohort of children and adolescents. The female preponderance of WFHF is clearly demonstrated in this analysis. Of note, only half of reported subjects required LT with the remaining responding to medical therapy. This fnding may be driven by biased reporting of cases describing the use of liver support systems. It may also refect subtle variations in WFHF disease defnition. Prospective studies are required to explore the true frequency and necessity of LT in WFHF.",acute liver failure;Asia;Australia;case study;child;clinical outcome;cohort analysis;Europe;female;fulminant hepatic failure;gene mutation;genotype;hemolytic anemia;human;liver support;liver transplantation;Medline;North America;phenotype;plasmapheresis;practice guideline;prospective study;publication;remission;school child;study design;systematic review;Web of Science;Wilson disease;alanine aminotransferase;alkaline phosphatase;aspartate aminotransferase;bilirubin;endogenous compound;penicillamine;Wilson disease protein,"Vandriel, S.;Ayoub, M.;Ling, S.;Ng, V.;Roberts, E.;Kamath, B.",2017,November,http://dx.doi.org/10.1097/MPG.0000000000001805,0,1,
3436,A Copper sensor for in vivo MRI,"Copper is the third most abundant transition metal in the body and a required nutrient for human growth and development.1 Copper is bound to a number of proteins and enzymes where it plays fundamental catalytic and structural roles.2 As a consequence of its redox activity, cellular copper homeostasis is tightly regulated and disruption causes a number of diseases including: Alzheimer's, Parkinson's, Prion, Menkes and Wilson disease.3 These diseases lead to variation of local concentration of copper ions from a few mM to several mM levels.4 Although the relationship between dynamic copper concentration and its physiological or pathological role have been studied extensively, information about the structural behavior in biological relevant conditions remain insufficiently understood due to lack of real-time copper detecting techniques.5 Magnetic Resonance Imaging (MRI) is a valuable medical diagnostic technique that allows noninvasive, three-dimensional visualization of whole organisms with high spatial and temporal resolution. The design of contrast agents that change T1 relaxation times of water protons in response to a given analyte is of major importance for MRI. Several responsive sensors have been reported in the literature including sensors for enzymatic activity, pH, pO2, glucose, lactate and nitric oxide.6 Specifically for copper sensing, the first generation of copper-activated MR sensors were reported by Que, et al.7,8 Although promising, the reported copper responsive MRI agents demonstrated interference from excess Zn<sup>2+</sup>, limiting its use in MR diagnostic applications for Cu<sup>2+</sup> .7 Here, we present a new copper responsive MR sensor, with a copper-selective recognition motif (L). This sensor shows high selectivity to copper ions, exhibits high relaxivity (r1) with a 42% increase in relaxivity upon binding to 1 equivalent of Cu<sup>2+</sup>. Interestingly, only when fully bound to Cu<sup>2+</sup>, the sensor presents a 310% increase in r1 (21 mM- 1.s-1) in the presence of physiological concentrations of Human Serum Albumin (HSA). With biochemical techniques, we have demonstrated also that GdL forms a Cu<sup>2+</sup>-mediated ternary complex with HSA (GdL-Cu<sup>2+</sup>-HSA). Initial in vivo studies were performed to confirm the ability of GdL to detect the variations of copper levels in liver using C57bl/6 wild type mice (Figure 1). We observed significant enhancement of contrast (~30%) in mice liver with GdL, suggesting a hepatobiliary clearance. When treated with a copper chelator (ATN-224) 2 hours prior to GdL injection, contrast was significantly reduced from liver (~50%) as shown in Figure 1. For the first time, a copper sensor could detect differences in extracellular copper levels in liver. Our results might pave the way for unique opportunities to explore the role of copper in the progression of many neurological disorders, including Wilson's disease.",Alzheimer disease;animal experiment;animal tissue;behavior;C57BL 6 mouse;catalysis;clearance;controlled study;disease course;DNA polymorphism;enzyme activity;homeostasis;human development;in vivo study;injection;liver;molecular recognition;mouse;nonhuman;nuclear magnetic resonance imaging;nutrient;oxidation reduction reaction;Parkinson disease;prion;protein blood level;relaxation time;sensor;wild type mouse;Wilson disease;biological product;choline tetrathiomolybdate;contrast medium;copper ion;cupric ion;endogenous compound;glucose;human serum albumin;lactic acid;nitric oxide;transition element;zinc ion,"Paranawithana, N.",2017,,http://dx.doi.org/10.1007/s11307-01-017-1138-y,0,0,
3437,Functional characterization of the ZEB2 regulatory landscape,"Zinc finger E-box-binding homeobox 2 (ZEB2) is a key developmental regulator of the central nervous system (CNS). Although the transcriptional regulation of ZEB2 is essential for CNS development, the elements that regulate ZEB2 expression have yet to be identified. Here, we identified a proximal regulatory region of ZEB2 and characterized transcriptional enhancers during neuronal development. Using chromatin immunoprecipitation sequencing for active (H3K27ac) and repressed (H3K27me3) chromatin regions in human neuronal progenitors, combined with an in vivo zebrafish enhancer assay, we functionally characterized 18 candidate enhancers in the ZEB2 locus. Eight enhancers drove expression patterns that were specific to distinct mid/hindbrain regions (ZEB2#e3 and 5), trigeminal-like ganglia (ZEB2#e6 and 7), notochord (ZEB2#e2, 4 and 12) and whole brain (ZEB2#e14). We further dissected the minimal sequences that drive enhancer-specific activity in the mid/hindbrain and notochord. Using a reporter assay in human cells, we showed an increased activity of the minimal notochord enhancer ZEB2#e2 in response to AP-1 and DLX1/2 expressions, while repressed activity of this enhancer was seen in response to ZEB2 and TFAP2 expressions. We showed that Dlx1 but not Zeb2 and Tfap2 interacts with Zeb2#e2 enhancer sequence in the mouse notochord at embryonic day 11.5. Using CRISPR/Cas9 genome editing, we deleted the ZEB2#e2 region, leading to reduction of ZEB2 expression in human cells. We thus characterized distal transcriptional enhancers and trans-acting elements that govern regulation of ZEB2 expression during neuronal development. These findings pave the path towards future analysis of the role of ZEB2 regulatory elements in neurodevelopmental disorders, such as Mowat-Wilson syndrome.",,"Yaacov, R. B.;Eshel, R.;Farhi, E.;Shemuluvich, F.;Kaplan, T.;Birnbaum, R. Y.",2018,Dec 26,https://dx.doi.org/10.1093/hmg/ddy440,0,0,
3438,Immunoglobulin A nephropathy secondary to Wilson's disease: a case report and literature review,"Immunoglobulin A nephropathy is the most common primary glomerulonephritis worldwide, and it can be associated with liver disease. However, cases of Immunoglobulin A nephropathy secondary to Wilson's disease are very rare. A 20-year-old Japanese man presented with microscopic hematuria, proteinuria, and renal dysfunction. A renal biopsy showed mesangial cell proliferation, immunoglobulin A deposition, and electron-dense deposit in the mesangial areas, all of which are consistent with Immunoglobulin A nephropathy. Computed tomography of the abdomen showed liver atrophy and splenomegaly, and the diagnosis of Wilson's disease was confirmed with decreased serum ceruloplasmin levels, increased urinary copper excretion, Kayser-Fleischer rings and copper deposition in the liver biopsy. The patient was treated successfully with trientine hydrochloride and zinc acetate and showed improvement in renal manifestations. Wilson's disease is a rare cause of secondary Immunoglobulin A nephropathy. We recommend that Wilson's disease should be considered the cause of secondary Immunoglobulin A nephropathy in juvenile patients with hematuria, proteinuria, and splenomegaly and suggest measuring the serum ceruloplasmin concentrations, urinary copper excretion, and evaluating Kayser-Fleischer rings in these patients.",,"Shimamura, Y.;Maeda, T.;Gocho, Y.;Ogawa, Y.;Tsuji, K.;Takizawa, H.",2018,Sep 25,https://dx.doi.org/10.1007/s13730-018-0365-7,0,0,
3439,[Wilson's disease or hepatolenticular degeneration],"Wilson's disease or hepatolenticular degeneration Abstract. Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism. The most common clinical presentations are liver disease and / or neuro-psychiatric manifestations. Pathophysiologically, Wilson's disease is caused by mutations in the ATP7B gene, which lead to defective biliary excretion of copper and subsequent accumulation of copper in the liver and in other organs. Its prevalence is approximately 1:30 000, however its penetrance, clinical presentation and disease severity vary widely, ranging from asymptomatic elevation of liver enzymes to cirrhosis or acute liver failure with or without neuro-psychiatric symptoms. For this reason, Wilson's disease should be suspected and ruled out in cases of indeterminate liver disease or neuropsychiatric disturbances. The diagnostic algorithms are complex and involve clinical tests, ophthalmologic examination (Kayser-Fleischer rings in split-lamp examination), blood and urine tests, genetic testing, imaging and histology. In compensated liver disease, treatment of Wilson's disease by copper depletion (chelators, zinc) is usually effective. In case of liver failure liver transplantation may be needed, which corrects the underlying error of copper metabolism. New drugs with improved efficacy and tolerability are in clinical development.",,"Mensing, B.;Nowak, A.;Zweifel, S.;Terracciano, L.;Bernsmeier, C.;Filipowicz Sinnreich, M.",2018,Nov,https://dx.doi.org/10.1024/0040-5930/a000995,0,0,
3440,Copper Complexes in Cancer Therapy,"Copper homeostasis is tightly regulated in both prokaryotic and eukaryotic cells to ensure sufficient amounts for cuproprotein biosynthesis, while limiting oxidative stress production and toxicity. Over the last century, copper complexes have been developed as antimicrobials and for treating diseases involving copper dyshomeostasis (e.g., Wilson's disease). There now exists a repertoire of copper complexes that can regulate bodily copper through a myriad of mechanisms. Furthermore, many copper complexes are now being appraised for a variety of therapeutic indications (e.g., Alzheimer's disease and amyotrophic lateral sclerosis) that require a range of copper-related pharmacological affects. Cancer therapy is also drawing considerable attention since copper has been recognized as a limiting factor for multiple aspects of cancer progression including growth, angiogenesis, and metastasis. Consequently, 'old copper complexes' (e.g., tetrathiomolybdate and clioquinol) have been repurposed for cancer therapy and have demonstrated anticancer activity in vitro and in preclinical models. Likewise, new tailor-made copper complexes have been designed based on structural and biological features ideal for their anticancer activity. Human clinical trials continue to evaluate the therapeutic efficacy of copper complexes as anticancer agents and considerable progress has been made in understanding their pharmacological requirements. In this chapter, we present a historical perspective on the main copper complexes that are currently being repurposed for cancer therapy and detail several of the more recently developed compounds that have emerged as promising anticancer agents. We further provide an overview of the known mechanisms of action, including molecular targets and we discuss associated clinical trials.",Animals;Antineoplastic Agents/ae [Adverse Effects];Antineoplastic Agents/ch [Chemistry];Antineoplastic Agents/me [Metabolism];*Antineoplastic Agents/tu [Therapeutic Use];Coordination Complexes;Copper/ae [Adverse Effects];Copper/ch [Chemistry];Copper/me [Metabolism];*Copper/tu [Therapeutic Use];Drug Design;Drug Repositioning;Humans;Molecular Structure;*Neoplasms/dt [Drug Therapy];Neoplasms/me [Metabolism];Neoplasms/pa [Pathology];Organometallic Compounds/ae [Adverse Effects];Organometallic Compounds/ch [Chemistry];Organometallic Compounds/me [Metabolism];*Organometallic Compounds/tu [Therapeutic Use];Structure-Activity Relationship;0 (Antineoplastic Agents);0 (Coordination Complexes);0 (Organometallic Compounds);789U1901C5 (Copper),"Denoyer, D.;Clatworthy, S. A. S.;Cater, M. A.",2018,02 05,https://dx.doi.org/10.1515/9783110470734-022,0,0,
3441,D-penicillamine combined with inhibitors of hydroperoxide metabolism enhances lung and breast cancer cell responses to radiation and carboplatin via H<sub>2</sub>O<sub>2</sub>-mediated oxidative stress,"D-penicillamine (DPEN), a copper chelator, has been used in the treatment of Wilson's disease, cystinuria, and rheumatoid arthritis. Recent evidence suggests that DPEN in combination with biologically relevant copper (Cu) concentrations generates H<sub>2</sub>O<sub>2</sub> in cancer cell cultures, but the effects of this on cancer cell responses to ionizing radiation and chemotherapy are unknown. Increased steady-state levels of H<sub>2</sub>O<sub>2</sub> were detected in MB231 breast and H1299 lung cancer cells following treatment with DPEN (100micro M) and copper sulfate (15micro M). Clonogenic survival demonstrated that DPEN-induced cancer cell toxicity was dependent on Cu and was significantly enhanced by depletion of glutathione [using buthionine sulfoximine (BSO)] as well as inhibition of thioredoxin reductase [using Auranofin (Au)] prior to exposure. Treatment with catalase inhibited DPEN toxicity confirming H<sub>2</sub>O<sub>2</sub> as the toxic species. Furthermore, pretreating cancer cells with iron sucrose enhanced DPEN toxicity while treating with deferoxamine, an Fe chelator that inhibits redox cycling, inhibited DPEN toxicity. Importantly, DPEN also demonstrated selective toxicity in human breast and lung cancer cells, relative to normal untransformed human lung or mammary epithelial cells and enhanced cancer cell killing when combined with ionizing radiation or carboplatin. Consistent with the selective cancer cell toxicity, normal untransformed human lung epithelial cells had significantly lower labile iron pools than lung cancer cells. These results support the hypothesis that DPEN mediates selective cancer cell killing as well as radio-chemo-sensitization by a mechanism involving metal ion catalyzed H<sub>2</sub>O<sub>2</sub>-mediated oxidative stress and suggest that DPEN could be repurposed as an adjuvant in conventional cancer therapy.","*Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology];Auranofin/pd [Pharmacology];*Breast Neoplasms/dt [Drug Therapy];Breast Neoplasms/pa [Pathology];Breast Neoplasms/rt [Radiotherapy];Buthionine Sulfoximine/pd [Pharmacology];Carboplatin/pd [Pharmacology];Catalase/me [Metabolism];Cell Line, Tumor;*Chelating Agents/pd [Pharmacology];Copper/ch [Chemistry];Copper/me [Metabolism];*Epithelial Cells/de [Drug Effects];Epithelial Cells/ph [Physiology];Female;Humans;Hydrogen Peroxide/me [Metabolism];*Lung Neoplasms/dt [Drug Therapy];Lung Neoplasms/pa [Pathology];Lung Neoplasms/rt [Radiotherapy];Oxidative Stress;*Penicillamine/pd [Pharmacology];Radiation;Thioredoxin-Disulfide Reductase/ai [Antagonists & Inhibitors];0 (Chelating Agents);3H04W2810V (Auranofin);5072-26-4 (Buthionine Sulfoximine);789U1901C5 (Copper);BBX060AN9V (Hydrogen Peroxide);BG3F62OND5 (Carboplatin);EC 1-11-1-6 (Catalase);EC 1-8-1-9 (Thioredoxin-Disulfide Reductase);GNN1DV99GX (Penicillamine)","Sciegienka, S. J.;Solst, S. R.;Falls, K. C.;Schoenfeld, J. D.;Klinger, A. R.;Ross, N. L.;Rodman, S. N.;Spitz, D. R.;Fath, M. A.",2017,07,https://dx.doi.org/10.1016/j.freeradbiomed.2017.04.001,0,0,
3442,Clinical efficacy and safety of Gandouling plus low-dose D-penicillamine for treatment of Wilson's disease with neurological symptoms,"To investigate the effect and safety of Gandouling plus low‐dose D‐penicillamine for treating patients with Wilson's disease (WD) who have neurological symptoms. WD patients with neurological symptoms were divided into two groups: a treatment group (n=53) and a control group (n=50). The treatment group received anti‐copper therapy with a combination of Gandouling and low‐dose D‐penicillamine (10 mg/kg), whereas the control group was with conventional dose D‐penicillamine (20 mg/kg) monotherapy. The clinical efficacies, adverse reactions, and results of the various hematological and biochemical investigations were recorded and analyzed statistically. Overall, 98.11% of the WD patients treated with the combined therapy experienced alleviation of their neurological condition (paralleled by a significantly improved Global Assessment Scale score or remained stable). Their white blood cell and platelet counts stabilized, and their liver function was improved or remained stable. The combined therapy also obviously promoted improved 24‐h urinary copper excretion. Only 15.09% of the WD patients with the combined therapy experienced adverse reactions, including neurological deterioration in one case (1.89%) and hepatic worsening in one case (1.89%), which was less frequent than that in the control group given conventional‐dose D‐penicillamine monotherapy. Treating WD patients with neurological symptoms using Gandouling plus low‐dose D‐penicillamine is effective and safe. Copyright © 2018 JTCM. All rights reserved.",,,2018,,,0,0,
3443,"Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial","BACKGROUND: PBT2 is a metal‐protein attenuating compound (MPAC) that affects the Cu2(+)‐mediated and Zn2(+)‐mediated toxic oligomerisation of Abeta seen in Alzheimer's disease (AD). Strong preclinical efficacy data and the completion of early, clinical safety studies have preceded this phase IIa study, the aim of which was to assess the effects of PBT2 on safety, efficacy, and biomarkers of AD. METHODS: Between December 6, 2006, and September 21, 2007, community‐dwelling patients over age 55 years were recruited to this 12‐week, double‐blind, randomised trial of PBT2. Patients were randomly allocated to receive 50 mg PBT2, 250 mg PBT2, or placebo. Inclusion criteria were early AD (mini‐mental state examination [MMSE] score between 20 and 26 points or Alzheimer's disease assessment scale‐cognitive subscale (ADAS‐cog) score between 10 and 25 points), taking a stable dose of acetylcholinesterase inhibitor (donepezil, galantamine, or rivastigmine) for at least 4 months, a modified Hachinski score of 4 points or less, and CT or MRI results that were consistent with AD. The principal outcomes were safety and tolerability. Secondary outcomes were plasma and CSF biomarkers and cognition. Analysis was intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00471211. FINDINGS: 78 patients were randomly assigned (29 to placebo, 20 to PBT2 50 mg, and 29 to PBT2 250 mg) and 74 (95%) completed the study. 42 (54%) patients had at least one treatment emergent adverse event (10 [50%] on PBT2 50 mg, 18 [62%] on PBT2 250 mg, and 14 [48%] on placebo). No serious adverse events were reported by patients on PBT2. Patients treated with PBT2 250 mg had a dose‐dependent (p=0.023) and significant reduction in CSF Abeta(42) concentration compared with those treated with placebo (difference in least squares mean change from baseline was ‐56.0 pg/mL, 95% CI ‐101.5 to ‐11.0; p=0.006). PBT2 had no effect on plasma biomarkers of AD or serum Zn(2+) and Cu(2+) concentrations. Cognition testing included ADAS‐cog, MMSE, and a neuropsychological test battery (NTB). Of these tests, two executive function component tests of the NTB showed significant improvement over placebo in the PBT2 250 mg group: category fluency test (2.8 words, 0.1 to 5.4; p=0.041) and trail making part B (‐48.0 s, ‐83.0 to ‐13.0; p=0.009). INTERPRETATION: The safety profile is favourable for the ongoing development of PBT2. The effect on putative biomarkers for AD in CSF but not in plasma is suggestive of a central effect of the drug on Abeta metabolism. Cognitive efficacy was restricted to two measures of executive function. Future trials that are larger and longer will establish if the effects of PBT2 on biomarkers and cognition that are reported here translate into clinical effectiveness.","Aged;Aged, 80 and over;Alzheimer Disease [*drug therapy, metabolism, physiopathology];Amyloid beta‐Peptides [*antagonists & inhibitors, metabolism];Biomarkers [analysis, blood, cerebrospinal fluid];Brain [*drug effects, metabolism, physiopathology];Clioquinol [administration & dosage, adverse effects, *analogs & derivatives, chemistry, pharmacology, therapeutic use];Dose‐Response Relationship, Drug;Double‐Blind Method;Down‐Regulation [drug effects, physiology];Female;Humans;Ionophores [administration & dosage, adverse effects];Male;Metals [*metabolism];Middle Aged;Peptide Fragments [antagonists & inhibitors, metabolism];Placebo Effect;Quinolines [*administration & dosage, adverse effects, chemistry];Safety;Treatment Outcome","Lannfelt, L.;Blennow, K.;Zetterberg, H.;Batsman, S.;Ames, D.;Harrison, J.;Masters, C. L.;Targum, S.;Bush, A. I.;Murdoch, R.;et al.",2008,,10.1016/S1474-4422(08)70167-4,0,0,
3444,DASH for asthma: a pilot study of the DASH diet in not-well-controlled adult asthma,"This pilot study aims to provide effect size confidence intervals, clinical trial and intervention feasibility data, and procedural materials for a full‐scale randomized controlled trial that will determine the efficacy of Dietary Approaches to Stop Hypertension (DASH) as adjunct therapy to standard care for adults with uncontrolled asthma. The DASH diet encompasses foods (e.g., fresh fruit, vegetables, and nuts) and antioxidant nutrients (e.g., vitamins A, C, E, and zinc) with potential benefits for persons with asthma, but it is unknown whether the whole diet is beneficial. Participants (n = 90) will be randomized to receive usual care alone or combined with a DASH intervention consisting of 8 group and 3 individual sessions during the first 3 months, followed by at least monthly phone consultations for another 3 months. Follow‐up assessments will occur at 3 and 6 months. The primary outcome measure is the 7‐item Juniper Asthma Control Questionnaire, a validated composite measure of daytime and nocturnal symptoms, activity limitations, rescue medication use, and percentage predicted forced expiratory volume in 1 second. We will explore changes in inflammatory markers important to asthma pathophysiology (e.g., fractional exhaled nitric oxide) and their potential to mediate the intervention effect on disease control. We will also conduct pre‐specified subgroup analyses by genotype (e.g., polymorphisms on the glutathione S transferase gene) and phenotype (e.g., atopy, obesity). By evaluating a dietary pattern approach to improving asthma control, this study could advance the evidence base for refining clinical guidelines and public health recommendations regarding the role of dietary modifications in asthma management.","Adolescent;Adult;Aged;Asthma [*diet therapy, immunology];Feasibility Studies;Female;Humans;Hypertension [diet therapy, prevention & control];Male;Middle Aged;Pilot Projects;Spirometry;Treatment Outcome;Young Adult","Ma, J.;Strub, P.;Lavori, P. W.;Buist, A. S.;Camargo, C. A.;Nadeau, K. C.;Wilson, S. R.;Xiao, L.",2013,,10.1016/j.cct.2013.04.008,0,0,
3445,Complementary Naturopathic Medicine for Periodontitis,"This study aims to assess selected naturopathic medicines for adult periodontitis and to identify variables that influence successful outcomes when traditional and alternative approaches to preventing and treating periodontal diseases are combined. Collaboration between Kaiser Permanente, Oregon Health Science University and the National College of Naturopathic Medicine provides an unsurpassed environment for such investigations. Periodontitis is a major cause of tooth loss and negatively impacts systemic health. The limitations of traditional periodontal treatment have compelled scientists and clinicians to investigate new remedies, and naturopathic medicine holds several promising interventions. Because they are used to improve elements of host resistance that are known to be important in periodontal health and disease, three naturopathic medicines are potential adjuncts in preventing and treating periodontitis. Connective tissue components are enzymatically degraded in periodontitis. In naturopathy, Connective Tissue Nutrient Formula (CTNF) (vitamins A, C and D, glucosamine sulfate, oligoproanthocyanindins, copper, zinc, manganese, boron, silicon, magnesium, and calcium) is prescribed specifically to enhance the integrity of key connective tissue elements and improve their resistance to degradation. Periodontitis begins when permeability of the oral sulcular epithelium permits pathogenic bacterial components to invade deeper periodontal connective tissues. In naturopathy, glutamine is prescribed to reduce oral‐intestinal epithelial membrane permeability. Chronic activation of the hypothalamic‐pituitary‐adrenal (HPA) axis during the stress response, is a risk factor for periodontitis. Adaptogenic herbs (AH) (Panax ginseng, Withania somnifera and Eleutherococcus senticosus) are prescribed by naturopathic physicians to reverse the impact of bacterial and psychosocial stressors. Because glutamine, CTNF and AH target pathophysiologic mechanisms known to underline periodontitis, they are compelling candidates in clinical and mechanistic investigations of complementary medicine approaches to the management of periodontitis. Kaiser Permanente adult periodontitis patients will serve as subjects and receive standard periodontal treatment. Three of the four randomly assigned groups will also receive supplements of glutamine, CTNF, or AH. We will determine the effects of these supplements on clinical outcomes (attachment loss, pocket depths, indicators of inflammation, plaque composition, need for periodontal surgery, acute periodontal problems, tooth loss). In addition to completing the battery of self‐report measures (stress, coping, quality of life), study subjects will provide samples of blood, saliva, gingival cervicular fluid and bacterial dental plaque. These samples will be examined as part of the Laboratory Core to identify biologic and genetic characteristics that correlate with successful outcomes. Storage of portions of the samples will allow future examination of additional variables as part of the Developmental Projects carried out as the Craniofacial Complementary & Alternative Center is established and Phase III trials are undertaken.",Periodontitis,Nct,2001,,,0,0,
3446,The Effect of a Nutritional Supplement in Individuals With Type 2 Diabetes Mellitus: a Pilot Study,"The prevalence of type 2 DM and related‐complications continues to increase. Diet is a significant factor in the aetiology of type 2 DM. Intakes of zinc and omega 3 fatty acids may modulate glycaemic control, lipid metabolism, and inflammatory processes in the disease. Zinc is involved in many biological processes that include enzyme action, stabilisation of cell membranes, regulation of gene expression, and cell signalling. Zinc supplementation has been demonstrated to improve glycaemic control in both animals and humans. The normalising effect of zinc on glucose homeostasis may relate to its involvement in insulin metabolism. Zinc functions in the synthesis, storage, secretion, and action of insulin. Omega‐3 also enhances glycaemic control and dietary supplementation with omega‐3 polyunsaturated fatty acids has been shown to improve insulin sensitivity in subjects with DM. Both zinc and omega‐3 function to mediate lipid metabolism. Zinc supplementation has been found to be associated with a beneficial increase in HDL cholesterol concentrations in individuals with type 2 DM. The mechanism may again involve insulin, which has been proposed as an independent predictor of plasma HDL. Omega‐3 directly activates transcription factors that regulate lipid metabolism and is known to decrease serum triglyceride levels in DM. Zinc appears to beneficially impact oxidative stress‐related parameters in DM via a range of mechanisms, including the regulation of copper,zinc superoxide dismutase, metallothionein, NF‐κB and nitric oxide signaling. The purpose of this pilot study is to explore the effect of zinc and omega 3 supplementation on hyperglycaemia, dyslipidaemia, chronic inflammation, and oxidative stress in a population with type 2 DM. This study will recruit 48 postmenopausal women with type 2 DM. Participants will be randomly allocated to one of 4 groups for a period of 12 weeks: placebo, zinc, omega 3, or zinc + omega 3 supplementation. Usual dietary intake will be assessed before and after the trial period using 2‐day estimated food records, which will be checked by a research dietitian. Blood samples will be collected from all participants at the start of the intervention (week 0) then at 4 weekly intervals (weeks 4, 8, 12) by qualified phlebotomists. Blood samples will be analysed for plasma zinc, plasma lipids and fatty acids, markers of inflammation and oxidative stress, and indicators of glycaemic control. An aliquot of blood will also be used for the measurement of zinc transporter mRNA levels utilising real‐time quantitative PCR techniques.","Diabetes Mellitus;Diabetes Mellitus, Type 2;Insulin Resistance;Zinc",Nct,2011,,,0,0,
3447,Efficacy and Safety of WTX101 Administered for 48 Weeks Versus Standard of Care in Wilson Disease Subjects,"This study is a randomized, rater‐blinded, multi‐center study assessing the efficacy and safety of an individualized WTX101 dosing regimen administered for 48 weeks, compared to SoC, in WD subjects aged 18 and older. Approximately 100 subjects will be enrolled at approximately 5 to 10 North American sites and 15 to 25 sites in the rest of the world. Subjects who complete the 48‐week treatment period will be offered to participate in an Extension Phase of the study to evaluate the long‐term safety and durability of treatment effect of WTX101. The primary objective is to evaluate the efficacy of WTX101 administered for 48 weeks, compared to SOC, on Cu control in WD subjects aged 18 and older. Copper control will be assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non‐ceruloplasmin‐bound copper (NCC) levels. For WTX101‐treated subjects, the NCC level will be corrected for the amount of Cu bound to the WTX101 tripartite complex (TPC) (NCCcorrected).",Hepatolenticular Degeneration,Nct,2018,,,0,0,
3448,Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson's Disease,"This is a multicenter, randomized, open label study with an active standard‐of‐care comparator. Stable patients who are already considered to be stable on their standard‐of‐care penicillamine chelation therapy for at least 1 year will enroll in the study and enter a 12‐week Penicillamine Baseline Period comprising of 1 month (4 weeks) run‐in period followed by a 2 month (8 weeks) evaluation period. During this time all patients will continue to take their current penicillamine under study conditions. At the end of the Penicillamine Baseline Period, patients who fulfill the protocol definition of being adequately controlled and tolerating penicillamine will be randomized in a 1:1 ratio to receive either TETA 4HCl or to continue to receive penicillamine. There is then a 24‐week Post‐randomization Phase comprising of a 1 month (4 weeks) run‐in period for both treatment arms and a 5 month (20 weeks) evaluation period. Patients who successfully complete the 24‐week Post‐randomization Phase of the study will have the opportunity to enter an 18 month (72 weeks) Extension Phase. Initially they continue to receive their allocated TETA 4HCl or penicillamine for a further 24 weeks (i.e., up to Week 60 of the study). Thereafter all patients will receive TETA 4HCl for 48 weeks (i.e., between Week 60 and Week 108). Study clinic visits occur every 6 months (24 weeks) for all patients (i.e., at Weeks 60, 84 and 108).",Hepatolenticular Degeneration;Penicillamine;Trientine,Nct,2018,,,0,0,
3449,Dietary copper intake in artificially fed infants,"Plasma concentrations of copper and zinc and leucocyte concentrations of zinc were measured in mothers during later pregnancy, at delivery, and 8‐10 weeks after birth, and plasma concentrations of copper and zinc were measured in their infants at delivery and 8‐10 weeks after birth. The 145 infants were either breast fed or fed one of two milk formulas supplying copper at different concentrations. None of the infants achieved the minimum copper intakes recommended by the World Health Organisation (WHO). At 2 months of age there were no major differences in growth or health detected in infants fed the different copper intakes. Infant birth weight correlated well with the ratio of maternal venous plasma zinc:maternal leucocyte zinc at delivery. Maternal venous plasma copper and zinc concentrations at birth correlated with umbilical venous plasma copper and zinc concentrations. Infants fed the higher copper content formulas had a low mean plasma zinc concentration without a significant increase in the mean plasma copper concentration. The present WHO recommendations regarding minimum copper intakes for infants fed formulas cannot be achieved with currently available formulas and are probably wrong.","Breast Feeding;Copper [*administration & dosage, blood];Diet;Female;Fetal Blood [analysis];Humans;Infant Food;Infant, Low Birth Weight [blood];Infant, Newborn [*blood, growth & development];Leukocytes [analysis];Male;Pregnancy;Zinc [blood]","Salim, S.;Farquharson, J.;Arneil, G. C.;Cockburn, F.;Forbes, G. I.;Logan, R. W.;Sherlock, J. C.;Wilson, T. S.",1986,,,0,0,
3450,"WTX101 in patients newly diagnosed with Wilson disease: final results of a global, prospective phase 2 trial","Background and Aims: Current therapies for Wilson disease, a disorder of copper metabolism resulting from ATP7B protein absence or dysfunction, are limited by efficacy, safety and multiple daily dosing. WTX101 (bis‐choline tetrathiomolybdate) is a first‐in‐class copper‐modulating oral agent that acts by increasing biliary copper excretion and reducing non‐ceruloplasmin bound serum copper (NCC) by forming complexes with albumin. Methods: In an open‐label, single‐arm, phase 2 study, 28 newly diagnosed patients withWilson disease (aged 18‐64 years, 46% male, 89% with some degree of neurological symptoms and around 50% with cirrhosis at baseline) received WTX101 monotherapy using a response‐guided dosing regimen with individualised doses of 15‐120 mg/day, mostly once daily. The primary endpoint was change from baseline to 24 weeks in NCC levels corrected for copper in tripartite tetrathiomolybdate‐copper‐albumin complexes in treated patients (NCCc). Model for End‐stage Liver Disease (MELD) and modified Nazer Score were used to monitor stability of liver disease and safety. Neurological status was evaluated using the Unified Wilson Disease Rating Scale (UWDRS). Results: At 24 weeks, 71% of patients treated with WTX101 either achieved or maintained normalised levels of NCCc or experienced a >=25% reduction from baseline NCCc (p < 0.001). Mean NCCc was significantly reduced from 3.6 uM at baseline to 0.9 uM at week 24 (p < 0.0001). Mean MELD score and modified Nazer score remained stable over the course of treatment indicating stabilisation of liver function. Reversible asymptomatic liver test elevations, observed in 39% of patients (at 30 mg/day dose or higher), were generally mild to moderate, and normalised with dose adjustments. Compared with baseline, patients showed significant improvements at week 24 in mean UWDRS disability score (6.6 vs. 4.1, p < 0.001) and neurological symptom score (22.8 vs. 16.6, p < 0.0001). No initial drug‐induced neurological worsening was seen. Conclusions: Final data from the first global, prospective clinical trial in Wilson disease indicate that WTX101 rapidly lowered and controlled NCCc resulting in improved disability and neurological status, with stable liver function and a favourable safety profile. These findings, together with its simple dosing regimen, indicate that WTX101 has the potential to address several unmet needs in the treatment of Wilson disease.",*Wilson disease;*prospective study;Adult;Albumin;Animal experiment;Animal model;Animal tissue;Conference abstract;Controlled clinical trial;Controlled study;Copper blood level;Diagnosis;Disability;End stage liver disease;Endogenous compound;Female;Human;Liver cirrhosis;Liver function;Male;Model For End Stage Liver Disease Score;Monotherapy;Nonhuman;Phase 2 clinical trial;Rating scale,"Weiss, K. H.;Askari, F. K.;Ferenci, P.;Ala, A.;Czlonkowska, A.;Nicholl, D.;Bronstein, J.;Bega, D.;Schilsky, M. L.",2017,,,0,0,3403
3451,A two-center randomized controlled feasibility trial of insulin pump therapy in young children with diabetes,"OBJECTIVE: Our goals were to determine if continuous subcutaneous insulin infusion (CSII), compared with those continuing multiple daily injections (MDIs), can be safely used in young children, if those on CSII will have superior glycemic control, if subjects using CSII will have less hypoglycemia for their level of control, and if families using CSII will report an improved quality of life. RESEARCH DESIGN AND METHODS: We conducted a randomized 1‐year feasibility trial comparing CSII with continuing MDIs in preschool children with a history of type 1 diabetes for at least 6 months' duration. Prospective outcomes included measures of overall glycemic control (HbA1c and continuous glucose monitoring system), the incidence of severe hypoglycemia and diabetic ketoacidosis, the percent of glucose values below 3.9 mmol/l, and the parents' report of quality of life. RESULTS: The 19 subjects' ages ranged from 1.7 to 6.1 (mean 3.6) years, duration of diabetes ranged from 0.6 to 2.6 (mean 1.4) years, and baseline HbA1c ranged from 6.7 to 9.6% (mean 7.9%). Seven subjects were male. Nine subjects were randomized to start CSII and 10 to continue on MDI. All baseline characteristics were well balanced. Overall metabolic control, diabetes quality of life, and the incidence of hypoglycemia were similar in the two groups. No subject had diabetic ketoacidosis, while one subject in each group had an episode of severe hypoglycemia. No CSII subject discontinued using the pump during or after the study. CONCLUSIONS: CSII can be a safe and effective method to deliver insulin in young children.","*insulin dependent diabetes mellitus/dm [Disease Management];*insulin dependent diabetes mellitus/dt [Drug Therapy];*insulin glargine/ae [Adverse Drug Reaction];*insulin glargine/cb [Drug Combination];*insulin glargine/do [Drug Dose];*insulin glargine/dt [Drug Therapy];*insulin glargine/pe [Pharmacoeconomics];*insulin glargine/sc [Subcutaneous Drug Administration];*insulin zinc suspension/ae [Adverse Drug Reaction];*insulin zinc suspension/cb [Drug Combination];*insulin zinc suspension/do [Drug Dose];*insulin zinc suspension/dt [Drug Therapy];*insulin zinc suspension/pe [Pharmacoeconomics];*insulin zinc suspension/sc [Subcutaneous Drug Administration];*insulin/ae [Adverse Drug Reaction];*insulin/cb [Drug Combination];*insulin/do [Drug Dose];*insulin/dt [Drug Therapy];*insulin/pe [Pharmacoeconomics];*insulin/sc [Subcutaneous Drug Administration];*isophane insulin/ae [Adverse Drug Reaction];*isophane insulin/cb [Drug Combination];*isophane insulin/do [Drug Dose];*isophane insulin/dt [Drug Therapy];*isophane insulin/pe [Pharmacoeconomics];*isophane insulin/sc [Subcutaneous Drug Administration];Article;Blood Glucose [drug effects, *metabolism];Child;Child, Preschool;Clinical article;Clinical trial;Controlled clinical trial;Controlled study;Diabetes Mellitus, Type 1 [blood, *drug therapy];Diabetic ketoacidosis/si [Side Effect];Disease duration;Disease severity;Drug dose regimen;Drug efficacy;Drug safety;Feasibility Studies;Female;Glucose blood level;Glucose/ec [Endogenous Compound];Glycated Hemoglobin A [analysis];Hemoglobin A1c/ec [Endogenous Compound];Human;Humans;Hypoglycemia [*chemically induced, prevention & control];Hypoglycemia/si [Side Effect];Incidence;Infant;Insulin Infusion Systems;Insulin infusion;Insulin pump;Intermethod comparison;Male;Metabolic regulation;Monitoring, Ambulatory;Multicenter study;Preschool child;Quality of life;Randomized controlled trial;Reproducibility of Results;Treatment Outcome","Wilson, D. M.;Buckingham, B. A.;Kunselman, E. L.;Sullivan, M. M.;Paguntalan, H. U.;Gitelman, S. E.",2005,,,0,0,
3452,Zinc-carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis,"Chelated zinc‐carnosine and vitamin E [GastriCalm (GCM); Teva Animal Health] is marketed as an anti‐emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double‐blinded, placebo‐controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica; Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n = 30) or placebo (n = 30) groups. All dogs received ~5 mg/kg ciclosporin (range, 3.5‐5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs >13.6 kg received one tablet once daily. GastriCalm or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty‐one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty‐seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P = 0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P < 0.05). 2010 The Authors. Journal compilation 2010 ESVD and ACVD.",*alpha tocopherol/dt [Drug Therapy];*atopic dermatitis/dt [Drug Therapy];*carnosine/ad [Drug Administration];*carnosine/dt [Drug Therapy];*cyclosporin/ae [Adverse Drug Reaction];*cyclosporin/dt [Drug Therapy];*dog disease/dt [Drug Therapy];*zinc/ad [Drug Administration];*zinc/dt [Drug Therapy];Animal;Animal disease;Appetite;Article;Chemically induced disorder;Clinical trial;Controlled clinical trial;Controlled study;Diarrhea/pc [Prevention];Diet supplementation;Dog;Drug combination;Drug effect;Immunosuppressive agent/ae [Adverse Drug Reaction];Immunosuppressive agent/dt [Drug Therapy];Randomized controlled trial;Vomiting/pc [Prevention],"Wilson, L. S.;Rosenkrantz, W. S.;Roycroft, L. M.",2011,,10.1111/j.1365-3164.2010.00910.x,0,0,
3453,A clinical study of bone mesenchymal stem cells for the treatment of hepatic fibrosis induced by hepatolenticular degeneration,"The efficacy of bone marrow mesenchymal stem cell (BMSC) on liver fibrosis in animal has been proven, but a few studies have been made in human body and few such researches in China. This study was designed to investigate the effect of BMSC treatment on hepatic fibrosis induced by hepatolenticular degeneration and the influence on serological indicators. Sixty patients with liver fibrosis induced by hepatolenticular degeneration were randomly divided into two groups, a penicillamine group and a BMSCs plus penicillamine group, with 30 patients in each. The therapeutic effects on hepatic fibrosis, liver function, and serological indicators were recorded before and after the treatment, and the data were compared. After treatment, serum levels of HA, PCIII, LN, CIV, TIMP‐1, and MMP‐1 were reduced in both groups (P < 0.05). However, cytokine levels in the BMSCs plus penicillamine group were significantly lower than those in the penicillamine group (P < 0.05). Combination therapy with BMSCs and penicillamine had a significant positive effect on liver fibrosis induced by hepatolenticular degeneration. Copyright © 2017 The Authors.",*Wilson disease;*bone marrow derived mesenchymal stem cell;*liver fibrosis/dt [Drug Therapy];*liver fibrosis/th [Therapy];*mesenchymal stem cell transplantation;Adult;Article;Collagen type 4/ec [Endogenous Compound];Controlled study;Drug fatality/si [Side Effect];Female;Fever/co [Complication];Fever/si [Side Effect];Granulocyte colony stimulating factor/dt [Drug Therapy];Human;Human cell;Hyaluronic acid/ec [Endogenous Compound];Interstitial collagenase/ec [Endogenous Compound];Laminin/ec [Endogenous Compound];Leukopenia/co [Complication];Leukopenia/dt [Drug Therapy];Liver fibrosis/dt [Drug Therapy];Liver function;Major clinical study;Male;Nausea/si [Side Effect];Pain/co [Complication];Penicillamine/ae [Adverse Drug Reaction];Penicillamine/ct [Clinical Trial];Penicillamine/dt [Drug Therapy];Penicillamine/po [Oral Drug Administration];Protein blood level;Randomized controlled trial;Rash/si [Side Effect];Therapy effect;Tissue inhibitor of metalloproteinase 1/ec [Endogenous Compound];Transforming growth factor beta1/ec [Endogenous Compound];Tumor necrosis factor/ec [Endogenous Compound];Vomiting/si [Side Effect],"Zhang, D.",2017,,10.4238/gmr16019352,0,0,69