record_id,pubmedID,title,authors,abstract,year,label_included,label_abstract_screening
1,10073329,Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin.,S K Gupta; G Sathyan,"Oxybutynin is used for the treatment of urge urinary incontinence. In this randomized, open-label, two-way crossover, multiple-dose study, the pharmacokinetics of a once-daily, controlled-release formulation, OROS oxybutynin chloride, was compared with that of immediate-release (IR) oxybutynin (Ditropan). Thirteen healthy female volunteers received three 5 mg OROS oxybutynin chloride tablets once daily for 4 days or IR oxybutynin 5 mg administered every 8 hours for 4 days. On day 1, with OROS oxybutynin chloride, mean plasma concentrations rose slowly over approximately 6 hours following dosing (mean Cmax 4.2 ng/mL) and remained fairly constant over the 24-hour dosing interval, whereas with IR oxybutynin, mean plasma concentrations rose rapidly within the first hour after dosing (mean Cmax 12.0 ng/mL), then declined. The mean oxybutynin degree of fluctuation was much lower for OROS oxybutynin chloride (78%) than for IR oxybutynin (371%). For both formulations, the plasma concentration-time profiles for the metabolite N-desethyloxybutynin paralleled those of oxybutynin but at higher concentrations. Steady-state oxybutynin concentrations were achieved by day 3 for both formulations. Mean area under the concentration-time curve (AUC) values for both oxybutynin and its metabolite were similar between day 1 and day 4 for each treatment, suggesting time-invariant pharmacokinetics. With OROS oxybutynin chloride, mean relative bioavailability was higher (153%) for oxybutynin and lower (69%) for N-desethyloxybutynin compared with IR oxybutynin. This increased bioavailability may be due to reduced first-pass metabolism; within 3 to 5 hours after dosing, OROS systems are thought to reach the colon, where cytochrome P450-mediated oxidation (oxybutynin's primary metabolic pathway) may be less extensive than in the small intestine. Fewer subjects reported any adverse event with OROS oxybutynin chloride than with IR oxybutynin (including dry mouth, oxybutynin's most frequently reported anticholinergic adverse effect).",1999.0,0,1
2,10079651,New drugs of 1998.,D A Hussar,"To provide information regarding the most important properties of the new therapeutic agents marketed in 1998. Published studies, drug information reference sources, and product labeling. In 1998, 44 new therapeutic agents were marketed. The indications and information on dosage and administration for each new agent are reviewed, as are the most important pharmacokinetic properties, adverse events, drug interactions, and other precautions. Practical considerations for the use of the new agents are also discussed. Where possible, the properties of the new drugs are compared with those of older drugs marketed for the same indications. A number of the new therapeutic agents marketed in 1998 have important advantages over older medications. An understanding of the properties of these agents is important for the pharmacist to effectively counsel patients about their use and to serve as a valuable source of information for other health professionals regarding these drugs.",1999.0,0,0
3,10160084,A review of the quality-of-life aspects of urinary urge incontinence.,W R Lenderking; J F Nackley; R B Anderson; M A Testa,"Urinary incontinence (UI) is prevalent and costly, occurring in 15 to 30% of the US population over the age of 60 years. Among people aged 15 to 64 years, UI occurs in 1.5 to 5% of men and 10 to 25% of women. Severe incontinence occurs in 6% of the general US population, and it is estimated that $US10 billion per year is spent in direct costs alone on care for these patients. This review presents a description of the various types of UI and describes the prevalence and costs of the condition. In addition, 3 approaches to assessing the impact of UI on quality of life are discussed, namely generic measures, disease-specific measures and qualitative approaches. We also review papers on UI and sexual functioning, UI in men, and some aspects of treatment. The review was conducted in the process of developing a new disease-specific measure for urinary urge incontinence (UUI). In general, the literature suggests that UUI has a greater impact than stress incontinence on quality of life, and that UI affects social and psychological functioning more than physical functioning. Only in a minority of individuals is the impact of UI disabling; however, most individuals with UI show significant reduction in their social functioning. Several studies suggest that the impact of UI is not solely a function of its severity, but also depends on individual coping abilities. Some studies also indicate that the social problems associated with UI grow with time, but it is not clear if that is a function of increasing severity of the condition, or the particular adaptations required for coping with this problem. An important distinction appears to be the ability of individuals to avoid public notice of their condition because of uncontrolled accidents. In summary, there is a need for a new measure of the quality-of-life impact of UUI that is based on the literature and on in-depth interviews with patients.",1995.0,0,0
4,10190648,"Tolterodine does not affect the human in vivo metabolism of the probe drugs caffeine, debrisoquine and omeprazole.",N Brynne; Y Böttiger; B Hallén; L Bertilsson,"To investigate the in vivo effect of treatment with tolterodine on debrisoquine 4-hydroxylation (an index of CYP2D6 activity), omeprazole 5-hydroxylation (CYP2C19), omeprazole sulphoxidation (CYP3A4) and caffeine N3-demethylation (CYP1A2). Twelve healthy male volunteers (eight extensive metabolisers [EMs] and four poor metabolisers [PMs] with respect to CYP2D6) received 4 mg tolterodine L-tartrate orally twice daily for 6 days. All subjects were EMs with respect to CYP2C19. The subjects received single oral doses of debrisoquine (10 mg), omeprazole (20 mg) and caffeine (100 mg) for determination of the appropriate metabolic ratios (MR). The drugs were given on separate consecutive days, before, during and after the co-administration of tolterodine. Mean serum tolterodine concentrations were 5-10 times higher in PMs than in EMs. Serum concentrations of the active 5-hydroxymethyl metabolite of tolterodine, 5-HM, were not quantifiable in PMs. The mean MR of debrisoquine (95% confidence interval) during tolterodine treatment was 0.50 (0.25-0.99) and did not differ statistically from the values before [0.49 (0.20-1.2)] and after tolterodine administration [0.46 (0.14-1.6)] in EMs. The mean MR of omeprazole hydroxylation and sulphoxidation or caffeine metabolism were not changed in the presence of tolterodine in either EMs or PMs. Debrisoquine and caffeine had no significant effect on the AUC(1,3 h) of either tolterodine or 5-HM, but during omeprazole administration small decreases (13-19%) in these parameters were seen. Tolterodine, administered at twice the expected therapeutic dosage, did not change the disposition of the probe drugs debrisoquine, omeprazole and caffeine and thus had no detectable effect on the activities of CYPs 2D6, 2C19, 3A4 and 1A2. Alteration of the metabolism of substrates of these enzymes by tolterodine is unlikely to occur.",1999.0,0,1
5,10193658,Pharmacological effects of tolterodine on human isolated urinary bladder.,M Yono; M Yoshida; Y Wada; H Kikukawa; W Takahashi; A Inadome; H Seshita; S Ueda,"Tolterodine, (R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine+ ++, is an antimuscarinic drug developed for the treatment of overactive bladder with symptoms of frequency, urgency and urge incontinence. We investigated the effects of tolterodine and its major active metabolite, DD 01 (PNU-200577), (R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3-phenylpropa namine, on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in human isolated urinary bladder smooth muscles, using the muscle bath technique. Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy due to malignant bladder tumor. The detrusor preparations were taken from the intact part of the dome region of the bladder. Carbachol (10(-9)-10(-2) M) caused concentration-dependent contraction of human detrusor smooth muscles. Tolterodine (10(-9)-10(-6) M), DD 01 (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-6) M), propiverine (10(-8)-10(-6) M), atropine (10(-9)-10(-6) M), pirenzepine (10(-8)-10(-5) M), methoctramine (10(-8)-10(-5) M) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (10(-9)-10(-6) M) caused typical shifts to the right of the concentration-response curves for carbachol, except for higher concentrations (10(-5) M) of oxybutynin and propiverine, which caused a decrease of about 30% of the maximum contractile responses to carbachol. All the slopes of the regression lines of Schild plots were close to unity, and the rank order of pA2 values was: atropine = DD 01 = tolterodine = 4-DAMP = oxybutynin > propiverine = pirenzepine > methoctramine. Tolterodine (10(-9)-10(-6) M) and DD 01 (10(-9)-10(-6) M) did not inhibit the KCl-induced (80 mM) and CaCl2-induced (5 mM) contractions, while oxybutynin (10(-8)-10(-5) M) and propiverine (10(-8)-10(-5) M) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contraction of human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 10(-6) M atropine, tolterodine and DD 01 did not inhibit the residual contractions induced by electrical field stimulation at any of the frequencies, while oxybutynin (10(-5) M) and propiverine (10(-5) M) significantly inhibited the atropine-resistant part of the contractions. The results suggest that the inhibitory effects of tolterodine and DD 01 are mediated only by their antimuscarinic action, which is equal to that of oxybutynin and significantly greater than that of propiverine, and that tolterodine and DD 01 have neither Ca2+ channel antagonist action nor inhibitory effect on the atropine-resistant part of the contractions in human detrusor smooth muscles. These findings support the usefulness of tolterodine as a therapeutic drug for overactive bladder with symptoms of frequency, urgency and urge incontinence.",1999.0,0,0
6,10206324,Serum protein binding of tolterodine and its major metabolites in humans and several animal species.,I Påhlman; P Gozzi,"The aim of this study was to determine in vitro protein binding of tolterodine and its 5-hydroxymethyl (5-HM) and N-dealkylated metabolites in serum from humans and several animal species at concentrations similar to those obtained in clinical and preclinical studies. Binding of tolterodine and the two metabolites to human serum albumin and alpha1-acid glycoprotein (AAG) was also assessed, as was binding of tolterodine to red blood cells. Ex vivo protein binding of tolterodine and 5-HM was determined in serum samples from healthy volunteers treated with oral tolterodine 4 mg twice daily for 8 days. Tolterodine exhibited high protein binding in human serum; the unbound fraction (f(u)) was 3.7%. The unbound fraction of tolterodine in cat and dog serum (1.5 and 2.1%, respectively) was lower compared with human serum; f(u) was higher in the other species investigated (rat, 22%; mouse, 16-17%; rabbit, 39%). The unbound fraction of 5-HM was much higher in serum from humans (36%) and all animal species investigated (mouse, 72%; rabbit, 68%; cat, 32%; dog, 45%). Binding of N-dealkylated tolterodine to proteins in human serum was intermediate (f(u) 14%). AAG was the major binding protein for tolterodine and 5-HM, and the degree of binding increased with increasing concentration of the protein. The association constant of 5-HM for AAG was lower than that of tolterodine (1.3 x 10(5) M(-1) versus 2.1 x 10(6) M(-1)). The blood:plasma tolterodine concentration ratio was 0.6 in both humans and dog; thus, a minor fraction of tolterodine was present in red blood cells compared with plasma (0.18 and 0.36, respectively). In the mouse, tolterodine was equally present in blood and plasma. In ex vivo samples, f(u) values for tolterodine (pH adjusted) varied between 1.6 and 4.9% (mean 2.8%), which could be explained by differences in AAG concentrations. There was good correlation between observed f(u) values for tolterodine and those predicted on the basis of AAG levels. Similar findings were observed for 5-HM.",2000.0,0,0
7,10210394,Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.,R Millard; J Tuttle; K Moore; J Susset; B Clarke; P Dwyer; B E Davis,"We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity. In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects. After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events. Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.",1999.0,1,1
8,10221366,,,,,0,0
9,10223495,Tolterodine in the treatment of overactive bladder: analysis of the pooled phase II efficacy and safety data.,G Larsson; B Hallén; L Nilvebrant,"To summarize the efficacy and safety of tolterodine from the pooled data of four multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group Phase II studies in patients with urodynamically proved overactive bladder (detrusor instability or detrusor hyperreflexia) and to analyze the concentration-effect relation. After a 1-week run-in period to establish baseline values, 319 patients were randomized to receive placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily. Micturition diary and urodynamic variables and subjective urinary symptoms were assessed after 2 weeks of treatment. Patients were classified as ""extensive"" or ""poor"" metabolizers of tolterodine on the basis of serum levels of tolterodine. A per-protocol analysis of efficacy in 262 patients showed dose-related improvements in micturition diary and urodynamic variables. A dosage of 4 mg twice daily was, however, associated with an increase in residual urinary volume. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable between placebo and tolterodine dosages of 2 mg twice daily. No serious drug-related adverse events were observed, and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. Changes in urodynamic variables were found to be related to the sum of unbound serum concentrations of tolterodine and its major active 5-hydroxymethyl metabolite. In poor and extensive metabolizers of tolterodine, exposure to the sum of these active moieties was similar, and the efficacy and safety profiles were comparable. The results of this pooled data analysis indicate that tolterodine offers an effective treatment for patients with urinary symptoms attributable to overactive bladder. The optimal dosage is 1 to 2 mg twice daily, irrespective of metabolic phenotype.",1999.0,0,0
10,10233562,Review. Quality-of-life aspects of the overactive bladder and the effect of treatment with tolterodine.,G Kobelt; I Kirchberger; J Malone-Lee,,1999.0,0,1
11,10332441,Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. OROS Oxybutynin Study Group.,R U Anderson; D Mobley; B Blank; D Saltzstein; J Susset; J S Brown,"We compared the efficacy and safety of once daily controlled and immediate release oxybutynin for incontinence. This multicenter, randomized, double-blind, active control, parallel study was designed to evaluate urge urinary incontinence episodes using a 7-day diary. A total of 97 women and 8 men 34 to 76 years old with urge incontinence or mixed incontinence with a clinically significant urge component were enrolled in the study. The number of weekly urge incontinence episodes decreased from 27.4 to 4.8 after controlled and from 23.4 to 3.1 after immediate release oxybutynin (p = 0.56), and total incontinence episodes decreased from 29.3 to 6 and from 26.3 to 3.8, respectively (p = 0.6). Weekly urge incontinence episodes from baseline to end of study also decreased to 84% after controlled and 88% after immediate release oxybutynin (p = 0.7). Continence was achieved in 41% of the controlled and 40% of the immediate release group (p = 0.9). Dry mouth of any severity was reported by 68 and 87% of the controlled and immediate release groups, respectively (p = 0.04), and moderate or severe dry mouth occurred in 25 and 46%, respectively (p = 0.03). Participants taking a single daily does of controlled release oxybutynin had similar reductions in urge incontinence and total incontinence episodes compared to those taking oxybutynin 1 to 4 times daily. A lower incidence of dry mouth was reported for controlled release oxybutynin.",1999.0,1,1
12,10338349,,,,,0,0
13,10344916,Urge incontinence. Quality of life and patients' valuation of symptom reduction.,R M O'Conor; M Johannesson; S L Hass; G Kobelt-Nguyen,"Previous studies have demonstrated the effect of incontinence, and urge incontinence in particular, on patients' quality of life. This study assessed the effects of urge incontinence on quality of life and measured the value of a reduction in symptoms. A self-administered questionnaire was mailed to 591 patients with urge or mixed incontinence. 495 (83.8%) surveys were returned with complete quality of life and symptom data. Of the total sample, 411 patients received the willingness-to-pay (WTP) survey, from which 257 (62.53%) returns were judged complete and reliable. Information was collected about the number of micturitions and urinary leakages. Health-related quality of life (HR-QOL) was measured using the Short Form 36 (SF-36) Health Survey. Socioeconomic characteristics were also recorded. Value was assessed with a binary WTP question. Quality of life among the sample population was significantly lower in 5 of 8 dimensions compared with the general US population, and was significantly related to the severity of the symptoms in 6 of 8 dimensions. The median (mean) willingness to pay was $US27.24 ($US87.74) per month for a 25% reduction in micturitions and leakages, and $US75.92 ($US244.54) per month for a 50% reduction in micturitions and leakages. As expected, the willingness to pay was significantly related to the size of the reduction in micturitions and leakages, and household income. Patients with incontinence perceive substantial benefits from a reduction in the number of micturitions and leakages.",1999.0,0,1
14,10350044,Oxybutynin enhances the metabolism of clomipramine and dextrorphan possibly by induction of a cytochrome P450 isoenzyme.,M Grözinger; S Härtter; C Hiemke; J Röschke,,1999.0,1,1
15,10363619,Importance of pharmacological and physicochemical properties for tolerance of antimuscarinic drugs in the treatment of detrusor instability and detrusor hyperreflexia--chances for improvement of therapy.,U Schwantes; P Topfmeier,"Antimuscarinic side-effects are relatively frequent problems in oral pharmacotherapy of detrusor instability and neurogenic dysfunction of the urinary bladder. Results of recent clinical trials demonstrate differences in tolerance between antimuscarinic drugs. It is the purpose of this paper to relate the available clinical data to the pharmacological and physicochemical properties of the different antimuscarinic drugs, in order to discuss the reasons for this enhanced tolerance and to make possible modes for improvement of antimuscarinic therapy plainly visible. Therefore, we reviewed the available literature using among others the computerized library systems Medline (National Library of Medicine, Bethesda, Maryland, USA) and Embase (Excerpta Medica, Amsterdam, the Netherlands). Differences in tolerance of oral antimuscarinic drugs may result from muscarine-receptor selectivity, organ selectivity, and pharmacokinetic as well as physicochemical properties. While the roles of m-receptor and organ selectivity need more detailed clarification, influences of differences in bioavailability and physicochemical properties on the tolerance of antimuscarinic drugs are more sufficiently investigated. Generally, tolerance as well as efficacy of antimuscarinic drugs seem to be a complex result of a combination of various pharmacological properties distinguishing the individual substances. The enhancement of tolerance of propiverine hydrochloride, tolterodine tartrate and trospium chloride compared to oxybutynin chloride seems to be reached by different modes, from which the molecular structure -- propiverine and tolterodine are tertiary amines, trospium chloride possesses a quarternary ammonium structure -- may be of great importance. First investigations with alternative transdermal and intravesical application routes show interesting possibilities for further improvement of antimuscarinic therapy in urological indications. In conclusion, from pharmacological and clinical data it becomes obvious that there are significant differences between antimuscarinic drugs, which are of clinical relevance and include possible starting points for the development of new drugs and application forms.",1999.0,0,1
16,10363730,An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder.,M M Goldenberg,"Detrusor instability, or urinary incontinence, is common in elderly patients, particularly elderly women. The clinical symptoms of overactive, or unstable, urinary bladder include urge urinary incontinence, urgency, and frequency. Mixed urinary incontinence, which comprises urge urinary incontinence and stress incontinence, is manifested by increased intraabdominal pressure on coughing or sneezing. The detrusor muscle of the bladder is under the control of the parasympathetic, or muscarinic, nervous system. The drug of choice in this condition is oxybutynin chloride, which has the ability to block acetylcholine released from parasympathetic nerves in the urinary bladder, preventing contractions of the muscle and exerting a direct spasmolytic effect on the bladder. A new extended-release oral tablet formulation, OROS oxybutynin, uses osmotic pressure to deliver the drug at a controlled rate over approximately 24 hours. It resembles a conventional tablet but has a two-part core consisting of a drug layer and below it, a ""push"" layer containing osmotically active components, the whole surrounded by a semipermeable membrane with a laser-drilled opening in the drug side. Water in the gastrointestinal tract enters the tablet and mixes with the drug to form a suspension. The ""push"" layer expands and pushes the suspended drug out of the orifice and into the gastrointestinal tract for eventual absorption. Pharmacokinetic studies have indicated a slow rise in mean plasma concentration of the isomer R-oxybutynin for 4 to 6 hours after a single dose of OROS oxybutynin, followed by maintenance of steady concentrations for up to 24 hours, minimizing the fluctuations between peak and trough associated with TID dosing of 5-mg immediate-release oxybutynin tablets. Efficacy and safety studies comparing the extended-release with the immediate-release formulation of oxybutynin demonstrated equivalent efficacy in patients with overactive urinary bladder. The adverse-event profile of oxybutynin is similar to that of a typical anticholinergic agent such as atropine--dry mouth, constipation, somnolence, blurred vision, headache, and gastrointestinal pain--although in 2 clinical studies, the incidence of dry mouth was less with the extended-release formulation. Once-daily dosing with OROS oxybutynin appears to be well tolerated and effective, as well as convenient, for the treatment of overactive bladder, particularly for elderly patients using multiple medications.",1999.0,0,0
17,10384969,Using flavoxate as primary medication for patients suffering from urge symptomatology.,P Fehrmann-Zumpe; K Karbe; G Blessman,"A drug utilization observation study collected data on a total of 1800 patients given flavoxate (Spasuret 200) over 2 weeks for urge incontinence. Efficacy and tolerance parameters were determined. A subgroup of 618 patients without urinary tract infections or benign prostatic hyperplasia were treated with flavoxate only. The subgroup (n = 618) showed a reduction of dysuria (37%), nocturia (53%), and both daytime (61%) and nighttime urge (69%). Bladder volume at first urge sensation increased by 55.1+/-58.8 ml (36%), which was comparable to data from the entire group (1800 patients). In 89.2% of all patients the residual urine volume was stable or decreased. Undesirable side effects occurred in 1.8% of cases. Both groups showed better results with flavoxate four times daily (800 mg), compared to three times daily (600 mg). Flavoxate is effective and well tolerated and causes no additional problems due to residual urine or side effects.",1999.0,0,0
18,10385263,Comparative pharmacology of recombinant human M3 and M5 muscarinic receptors expressed in CHO-K1 cells.,N Watson; D V Daniels; A P Ford; R M Eglen; S S Hegde,"1. Affinity estimates were obtained for several muscarinic antagonists against carbachol-stimulated [3H]-inositol phosphates accumulation in Chinese hamster ovary (CHO-KI) cells stably expressing either human muscarinic M3 or M5 receptor subtypes. The rationale for these studies was to generate a functional antagonist affinity profile for the M5 receptor subtype and compare this with that of the M3 receptor, in order to identify compounds which discriminate between these two subtypes. 2. The rank order of antagonist apparent affinities (pK(B)) at the muscarinic M5 receptor was atropine (8.7) > or =tolterodine (8.6) = 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 8.6)> darifenacin (7.7) > or =zamifenacin (7.6)>oxybutynin (6.6)= para-fluorohexahydrosiladifenidol (p-F-HHSiD, 6.6)>pirenzepine (6.4) > or = methoctramine (6.3)=himbacine (6.3)>AQ-RA 741 (6.1). 3. Antagonist apparent affinities for both receptor subtypes compare well with published binding affinity estimates. No antagonist displayed greater selectivity for the muscarinic M5 subtype over the M3 subtype, but himbacine, AQ-RA 741, p-F-HHSiD, darifenacin and oxybutynin displayed between 9- and 60 fold greater selectivity for the muscarinic M3 over the M5 subtype. 4. This study highlights the similarity in pharmacological profiles of M3 and M5 receptor subtypes and identifies five antagonists that may represent useful tools for discriminating between these two subtypes. Collectively, these data show that in the absence of a high affinity M5 selective antagonist, affinity data for a large range of antagonists is critical to define operationally the M5 receptor subtype.",1999.0,0,0
19,10385348,Drug eruption due to flavoxate hydrochloride.,U Enomoto; Y Ohnishi; M Kimura; A Kawada; A Ishibashi,,2000.0,0,1
20,10393480,Pharmacological management of incontinence.,J Sullivan; P Abrams,"Many patients with incontinence do not need surgery - for these patients symptoms can often be considerably improved by conservative measures, including drugs. Several different pharmacological actions are potentially useful depending on the underlying cause of the incontinence: a) Detrusor instability (DI) responds to drugs reducing bladder contractility: Anticholinergic agents, e.g. oxybutynin and tolterodine, act at postganglionic parasympathetic cholinergic receptor sites on the detrusor muscle, reducing the strength of the detrusor contraction. Tricyclic antidepressants, e.g. imipramine, have anticholinergic effects, block presynaptic uptake of amine neurotransmitters and directly inhibit detrusor muscle. Alpha-adrenergic antagonists may have a role to play by dual actions on bladder overactivity (due to altered receptor function) and by reducing outlet resistance. b) Genuine stress incontinence (GSI) may be treated using alpha-adrenergic agonists, e.g. phenylpropanolamine, to increase outlet resistance by stimulating smooth muscle of the urethra and bladder neck. c) In nocturnal enuresis reduction of nocturnal urine output with the anti-diuretic hormone (ADH) analogue DDAVP (1-deamino, 8-arginine vasopressin) is beneficial. d) Bladder emptying may be facilitated in patients with retention and 'overflow' incontinence by alpha-adrenergic antagonists, which reduce outlet resistance, and perhaps by parasympathomimetics, e.g. bethanecol. e) In postmenopausal women, systemic oestrogen replacement reduces filling symptoms including urge incontinence. Evidence for oestrogen replacement alone in GSI is lacking, but combination with alpha-agonists is beneficial in milder GSI. For the future, tolterodine and other new anticholinergics offer the hope of treatment for DI with fewer of the side effects that limit the use of established drugs. Better understanding of the pathophysiology of DI may provide new targets for drug therapy, such as hyperpolarisation of detrusor muscle membrane. Alpha-agonists may find a greater role in the future, as may ADH analogues for noctural symptoms.",1999.0,0,0
21,10397381,Treatment of urge incontinence in Veterans Affairs medical centers.,D C Malone; G J Okano,"Urinary incontinence has far-reaching medical, psychological, social, and economic effects. The objectives of this descriptive study were to examine utilization patterns and discontinuation rates of various pharmacologic agents used to treat symptoms of overactive bladder, primarily urge incontinence (UI), and to estimate the prevalence of urinary incontinence in the study population. Patient-level data regarding specific drugs used to treat UI and the use of diapers or pads over a 9-month period from October 1995 to May 1996 were retrospectively extracted from the medication databases of 9 Department of Veterans Affairs medical centers. A total of 2233 male patients were included in the analyses. Most patients were receiving oxybutynin chloride (39.8%), dicyclomine hydrochloride (16.0%), or imipramine hydrochloride (13.9%), and the remaining 30.3% were using flavoxate hydrochloride, propantheline bromide, hyoscyamine sulfate, and adult diapers or pads. Overall, 72.1% of patients had been prescribed daily dosages within the recommended dosing ranges for these medications. The majority (91.3%) of patients had not switched to another UI medication during the study period. Based on a chronic disease index, 47.6% of patients had 2 or fewer chronic diseases. Using pooled prevalence estimates, the estimated percentage of patients who had ever experienced UI in this population ranged from 7.4% to 20.8%; however, a considerably smaller percentage were taking medications for the treatment of UI. The results of this study suggest that oxybutynin, dicyclomine, and imipramine are the agents most commonly used to treat urinary incontinence within Veterans Affairs medical centers. The majority of patients who received a prescription for one of these drugs did not routinely refill the medication over the course of the study. There are many reasons for patients not to refill a prescription (eg, ineffectiveness, side effects, complications, obtaining the drug from another source), but the present study did not address the causes.",1999.0,0,0
22,10428737,Update in general internal medicine.,D Altkorn; K Roach; S Stern; W Levinson,,2000.0,0,0
23,10436424,Clinical efficacy of oxybutynin on sensory urgency as compared with that on motor urgency.,K Hashimoto; N Ohnishi; A Esa; T Sugiyama; Y Park; T Kurita,"Anticholinergic drug is widely accepted as an effective medication for frequency, urgency and urge incontinence related to detrusor overactivity (motor urgency). In order to elucidate whether anticholinergic drug is also effective for these symptoms related to bladder hypersensitivity (sensory urgency), clinical efficacy of oxybutynin on sensory urgency was compared with that on motor urgency. Twenty-four patients with sensory urgency, and 53 patients with motor urgency were treated with oxybutynin (6 mg/day) for 4 weeks and subjective and objective efficacies were evaluated. Subjective parameters were quantified with urge score (grade 0-3) and daily numbers of voiding and incontinence. Objective efficacies were evaluated with pre-/ postcomparison of cystometric parameters. Excellent or good overall efficacy was obtained in 62.5% (15/24) of the sensory urgency group and 60.4% (32/53) of the motor urgency group. There was no statistical difference between these two groups. Objective cystometric parameters, bladder volume at first sensation and maximum cystometric capacity, statistically improved after the treatment in both groups. The results suggest that oxybutynin works as well on sensory urgency as it does on motor urgency.",1999.0,0,0
24,10458657,"Tolterodine for overactive bladder: time to onset of action, preferred dosage, and 9-month follow-up.",A Atan; B R Konety; J R Erickson; T Yokoyama; D Y Kim; M B Chancellor,"This is a prospective study of 28 patients who had urinary frequency (>8 times/day) and either urgency or urge incontinence (>1 time/day). After a 2-week run-in period (visit 1), the patients were started on tolterodine 1 mg twice a day (bid) (visit 2). They were followed at 4 and 8 weeks (visits 3 and 4). The patients were contacted by telephone 1 week after visit 2. Tolterodine was increased to 2 mg bid if the patient had incomplete improvement at either the initial phone call or during visit 3. Evaluation criteria were daily micturition charts including urinary frequency, nocturia, leakage episodes, average urine volume per day, and average voided volume. Tolterodine was well tolerated without side effects in 20 (80%) of 28 patients. Eight patients (20%) dropped out after enrollment because of side effects in 3, no improvement in 2, and missing visits (>1) in 3. Drug dosage in the 20 patients who tolerated tolterodine was 1 mg bid in 3 and 2 mg bid in 17 (85%). According to micturition charts, urinary frequency, nocturia, and leakage episodes decreased significantly after tolterodine treatment, whereas average urine volume per day and average voided volume did not change significantly. There were no electrocardiographic or biochemical abnormalities due to tolterodine treatment. Mean follow-up was 9.4 months. All 20 patients who tolerated tolterodine continue to take the medication without significant side effects. We conclude that tolterodine is well tolerated and effective for overactive bladders. Two milligrams bid is the dosage preferred by the majority of patients and the onset of action is seen within 1 week of treatment. Long-term compliance and efficacy are excellent, with no dropout in >9 months of follow-up.",1999.0,0,1
25,10459465,Neurogenic bladder dysfunction.,H G Madersbacher,"Urodynamics are still essential for diagnosis and prognosis of neurogenic lower urinary tract-dysfunction and can not be replaced by other means of investigation so far, neither by a thorough clinical investigation nor by sophisticated means like magnetic resonance imaging. The findings with clinical investigations are specific, but not sensitive enough, and the spinal cord lesions may sometimes be beyond the resolution of magnetic resonance-scanning. Pharmacotherapy is still the corner stone in the management of detrusor hyperreflexia. Further studies with tolterodine, oxybutynin, trospiumchloride and propiverine have increased our knowledge about these substances. Capsaicin was proved to be the effective substance and not the alcoholic solution, which serves as a carrier. Intrathecal clonidine may represent a new conservative reversible alternative treatment for detrusor hyperreflexia. Experiments with detrusor strips from end-stage MMC-patients may explain the relative resistance of the low compliant bladder to the common anticholinergic/spasmolytic therapy. The differential indication for bladder augmentation, either using segments of the gastrointestinal-tract or performing a partial detrusor myectomy is ongoing, favourable results are reported for both techniques. Sacral posterior root rhizotomy is able to abolish detrusor hyperreflexia and therefore recommended for tetra- and paraplegics, however autonomic dysreflexia, if present, can not be totally abolished. Collagen injections for neuropathic sphincter incompetence can not be recommended as demonstrated in children with congenital neuropathy, a new design of an artificial sphincter must stand the test of time.",1999.0,0,0
26,10461546,Metabolism-based drug interactions involving oral azole antifungals in humans.,M Strolin Benedetti; M Bani,,1999.0,0,1
27,10475346,Evaluation of a new once-daily formulation of oxbutynin for the treatment of urinary urge incontinence. Ditropan XL Study Group.,D M Gleason; J Susset; C White; D R Munoz; P K Sand,"To evaluate in a 1 6-center, single-treatment study once-daily controlled-release oxybutynin (Ditropan XL) for urinary urge incontinence. Two hundred fifty-six participants with urge incontinence or mixed incontinence with a significant urge component were treated. After baseline measurements, participants converting from conventional oxybutynin started Ditropan XL at their previous oxybutynin dose; others started at 5 mg/day. Doses were adjusted until participants reached a maintenance dose that produced continence or the best balance between continence and side effects. This dose was continued for 12 weeks. Effectiveness was assessed by urinary diaries. Effectiveness was achieved across all doses studied (5 to 30 mg/day), with 70.8% of participants using maintenance doses of 5 to 15 mg/day. Mean urge incontinence episodes per week decreased from 18.8 at baseline to 3.9 in maintenance week 1, 2.7 in week 4, and 2.8 at the end of the study. For those participants who reported urge incontinence episodes at baseline but were free of urge incontinence at maintenance week 1, 31% remained free of urge incontinence at every subsequent assessment. Participants who converted from other medications showed symptomatic improvement after conversion. At some time during the study, 58.6% of participants reported dry mouth, with 23.0% of participants rating it moderate or severe. Only 1.6% of participants discontinued the medication because of dry mouth. Ditropan XL treatment reduced the number of incontinence episodes. Maximum benefit was demonstrated by maintenance week 4 and was sustained through 12 weeks of maintenance therapy.",1999.0,1,1
28,10479880,[Oxybutinin-desmopressin association in the treatment of primary nocturnal enuresis with diurnal urination disorders].,E De Grazia; M Cimador,"Since most of the children observed in our Centre present enuresis with voiding disturbance, we carried out a study where these patients were treated with the DDAVP + Oxybutinin association. We have treated 89 children with enuresis and voiding disturbances (urge incontinence, voiding urgency, urinated > 7 times a day), administering a drugs combination of desmopressin (20 micrograms/daily) and oxybutinin (0.3-0.6 mg/kg/bid or tid) for a variable period, depending on response to the treatment. The results demonstrate the efficacy of this association: we have observed a reduction in average bed wetting nights from 23.4 nights/month to 6.4 wet nights after 1 month, to 3.8 ad 2.9 respectively after 3 and 6 months from the beginning. Moreover we obtained a recovery of all daily voiding disturbances after 3 months. Fifty percent of children were cured after 4 months of therapy and finally 93.2% recovered at 6 months. On the other hand, 2 children were no-responders to the therapy even after 9 months of combined drugs administration. Based on these results we can affirm that children with nocturnal enuresis and voiding disturbance can be treated with this combined therapy. Actually, the reduction of urinary output and thus lower bladder filling, due to the desmopressin, decreases the onset of uninhibited bladder contractions and enhances oxybutinin activity.",1999.0,0,0
29,10480828,Recent advances. Gynaecology.,C Kelleher; P Braude,,1999.0,0,0
30,10510109,"A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence.",H Madersbacher; M Halaska; R Voigt; S Alloussi; K Höfner,"To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a randomized, double-blind placebo-controlled clinical trial. In all, 366 patients (149 on propiverine, 145 oxybutynin and 72 placebo, ratio 2:2:1) with urgency and urge incontinence were recruited in 32 study centres. Propiverine (group 1, 15 mg three times daily), oxybutynin (group 2, 5 mg twice daily) or placebo (group 3) were administered for 4 weeks, using the double-dummy technique. The dosages were selected specifically to compare the tolerability profile of propiverine with the commonly used therapeutic dosage of oxybutynin. Tolerability was assessed by directly questioning the patients about adverse events at four visits (V-1 before and V0 after a 1-week 'washout' period, V1 after 1 week and V4 after 4 weeks of treatment) during a 5-week surveillance period, and by tolerability ratings of the physicians. Efficacy was assessed using urodynamics at V0 and V4, evaluating the cystometric bladder capacity at maximal and first desire to void, and postvoid residual urine, according to the criteria of the International Continence Society. Additionally, a voiding protocol, overall assessment of clinical symptomatology and efficacy ratings by the physicians were documented. A remarkably high percentage of adverse events was reported in the washout period (VO: 13%, 16% and 18% in groups 1-3, respectively). At V4, the clinically most relevant symptom (dry mouth) occurred in 53% of patients in group 1, in 67% of group 2 and in 28% of group 3. Furthermore, dry mouth was less severe in group 1 than group 2. In contrast to groups 2 and 3, only patients in group 1 showed increasing tolerability during the treatment (from V1 to V4). These tolerability results were further supported by the overall tolerability assessment ('very good' or 'good' tolerability in 67% of group 1, in 59% of group 2 and in 83% of group 3). The urodynamic assessment of efficacy (comparing V0 and V4) showed a statistically significant increase in the mean (sd) maximal cystometric bladder capacity in group 1, being 222 (77) mL at V0 and 311 (125) mL at V4, an increase of 89 (108) mL, and in group 2, at 226 (75) mL and 322 (123) mL, an increase of 96 (106) mL, compared with group 3, at 211 (77) mL and 263 (93) mL, an increase of only 52 (92) mL. The cystometric bladder capacity at first desire to void also increased in group 1 (93 to 160 mL) and group 2 (89 to 160 mL), whereas in group 3 there were only minor changes (93 to 120 mL). Changes in the residual urine volume within and between the treatment groups were minimal and clinically irrelevant. The overall assessment of efficacy showed significant differences between the drugs when compared with placebo. Propiverine is a safe and effective drug in the treatment of urgency and urge incontinence; it is as effective as oxybutynin, but the incidence of dry mouth and its severity is less with propiverine than with oxybutynin. The availability of alternative pharmacotherapeutics such as propiverine should reduce the therapeutic failure rate and improves the success rate in the treatment of patients suffering from urgency and urge incontinence.",1999.0,1,1
31,10510920,Advantages and risks of ileovesicostomy for the management of neuropathic bladder.,A Atan; B R Konety; A Nangia; M B Chancellor,"To evaluate the efficacy and complications of ileovesicostomy in patients with neurogenic bladder dysfunction. Fifteen consecutive neurologically impaired patients (8 from multiple sclerosis, 4 from spinal cord injury, 3 from other causes) with complications of previous bladder management underwent ileovesicostomy. There were 10 women and 5 men. All patients were either poor candidates for or refused continent urinary diversion or bladder augmentation cystoplasty. At a mean follow-up of 23.2 months, 14 of 15 patients had low-pressure urine drainage through their ileovesicostomy. Four women with documented preoperative detrusor hyperreflexia had postoperative intermittent mild urge incontinence per native urethra. They did not require any further treatment, except for oral anticholinergic drugs (oxybutynin and tolterodine). Because of persistent severe urge incontinence, 1 woman required conversion of her ileovesicostomy to an ileal conduit with concurrent cystectomy. The ileovesicostomy of another myelodysplastic man who had four failed artificial urinary sphincters in the past was also converted to an ileal conduit because of persistent urethroperineal fistula despite perineal urethral closure. Renal function was preserved in all patients. Long-term complications were stomal stenosis in 2 patients, bladder and kidney stone formation in 5, and symptomatic urinary tract infections in 3. Ileovesicostomy can be safely performed in neurologically impaired women and men. Severe preoperative detrusor hyperreflexia with urge incontinence appears to be a risk factor for persistent urge incontinence postoperatively in women. Continued routine urologic surveillance for infection and stones is mandatory. Ileovesicostomy is a versatile procedure for neurologically impaired patients, because it can be converted to a conventional ileal conduit if necessary. In addition, in cases of neural recovery, the ileal ""chimney"" can be excised and the patient's original lower urinary tract would be preserved.",1999.0,0,0
32,10512072,,,,,0,0
33,10515528,Safety review of the oral antifungal agents used to treat superficial mycoses.,A K Gupta; N H Shear,,1999.0,0,0
34,10534221,Tolterodine use for symptoms of overactive bladder.,J M Ruscin; N E Morgenstern,"To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder. Published articles and abstracts were identified from a MEDLINE search (January 1980-October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration-approved product labeling and the manufacturer were also used in the absence of published data. Clinical studies of tolterodine involving human subjects were evaluated. Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents. Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.",1999.0,0,0
35,10543335,Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder.,H P Drutz; R A Appell; D Gleason; I Klimberg; S Radomski,"This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks' treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.",1999.0,1,1
36,10550530,Oxybutynin disrupts learning and memory in the rat passive avoidance response.,T Sugiyama; Y C Park; T Kurita,"oxybutynin, a drug for pollakisuria and urinary incontinence, has a potent antimuscarinic activity. This study was aimed to determine whether this drug disrupts learning and memory in rats, because antimuscarinic activity in the central nervous system is considered to cause amnesia in humans. male Wistar rats were given oxybutynin or scopolamine as a reference drug, and subjected to the acquisition trial of step-through passive avoidance response (PAR). Twenty-four hours later the retention test for each rat was performed and the latency time in the PAR was measured. oral administration of oxybutynin at 30 mg/kg or higher and intraperitonial injection of scoplamine at 0.5 mg/kg caused a significant decrease in the latency time in the retention test. oxubutynin caused a decrease in the retention time of the PAR in a manner similar to scopolamine, indicating that oxybutynin may cause disruption of learning and memory.",1999.0,0,0
37,10553641,Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method.,T Ishikawa; Y Watanabe; N Utoguchi; M Matsumoto,"The aim of this study was to prepare, using taste-masked granules, tablets which can rapidly disintegrate in saliva (rapidly disintegrating tablet), of drugs with bitter taste (pirenzepine HCl or oxybutynin HCl). The taste-masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100) by the extrusion method. None of the drugs dissolved from the granules (% of dissolved, < 5%) even at 480 min at pH 6.8 in the dissolution test. However, the drugs dissolved rapidly in the medium at pH 1.2 in the dissolution test. Rapidly disintegrating tablets were prepared using the prepared taste-masked granules, and a mixture of excipients consisting of crystalline cellulose (Avicel PH-102) and low-substituted hydroxypropylcellulose (L-HPC, LH-11). The granules and excipients were mixed well (mixing ratio by weight, crystalline cellulose: L-HPC = 8:2) with 1% magnesium stearate, and subsequently compressed at 500-1500 kgf in a single-punch tableting machine. The prepared tablets (compressed at 500 kgf) containing the taste-masked granules have sufficient strength (the crushing strength: oxybutynin tablet, 3.5 kg; pirenzepine tablet, 2.2 kg), and a rapid disintegration time (within 20 s) was observed in the saliva of healthy volunteers. None of the volunteers felt any bitter taste after the disintegration of the tablet which contained the taste-masked granules. We confirmed that the rapidly disintegrating tablets can be prepared using these taste-masked granules and excipients which are commonly used in tablet preparation.",1999.0,0,0
38,10569603,Use of polydimethylsiloxane for endoscopic treatment of neurogenic urinary incontinence in children.,J M Guys; J Simeoni-Alias; A Fakhro; A Delarue,"We report on the injection of polydimethylsiloxane for endoscopic treatment of urinary incontinence in children with neurogenic bladder and determine the optimal criteria for patient selection. We have treated 17 boys and 16 girls since 1995. The etiology of incontinence was spina bifida in 24 cases. Previous surgery was performed in 18 patients, including bladder neck reconstruction in 15 and bladder augmentation in 9. Mean patient age at injection was 13 years (range 7 to 17). We administered 1, 2 and 3 injections in 21, 11 and 1 patients, respectively. Mean volume at each injection was 3.2 cc. Mean interval between injections was 6 months (range 3 to 15). In all cases injection was done transurethrally. Followup ranged from 6 to 41 months (median 16). A total of 11 patients (33.3%) are dry (continence for greater than 4 hours and no urinary pad use during the day) and 8 (24.2%) are improved (continence for 2 to 3 hours and minimal pad use). Results are poor in 14 cases. Overall previous bladder neck surgery or preoperative detrusor hyperactivity did not influence results. Good results were mainly associated with female gender (47.4% of girls versus 10.5% of boys achieved cure). Injection of polydimethylsiloxane at the bladder neck resulted in continence in 33% of neurogenic bladder cases. Better results occurred in girls and injection did not compromise other surgical procedures. Polydimethylsiloxane seems more suitable than bovine collagen due to potential problems with biological product use.",1999.0,0,0
39,10569604,Desmopressin resistant enuresis: pathogenetic and therapeutic considerations.,T Nevéus; G Läckgren; T Tuvemo; U Olsson; A Stenberg,"We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication. We gave 33 children with monosymptomatic nocturnal enuresis resistant to the standard 0.4 mg. oral dose of desmopressin 0.4 and 0.8 mg. desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion. The time of enuresis or nocturia was documented. All 9 children who had at least 1 dry treatment period during the randomized portion of the study then received open label treatment with 0.8 mg. desmopressin. Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment. Average time between bedtime and voiding was 5.0, 5.6 and 5.0 hours during the nights with placebo, and 0.4 and 0.8 mg. desmopressin, respectively (p = 0.12). Of the 9 children subsequently treated with 0.8 mg. desmopressin 5 became completely dry. Of the remaining 28 children given anticholinergic treatment 20 responded. Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis. This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability. A subgroup of enuretic children responds to high but not normal doses of desmopressin.",1999.0,0,0
40,10571650,Visual hallucinations at the onset of tolterodine treatment in a patient with a high-level spinal cord injury.,B Malavaud; H Bagheri; J M Senard; J P Sarramon,,1999.0,0,0
41,10573314,Tolterodine-warfarin drug interaction.,V J Colucci; M P Rivey,"To report two cases of warfarin therapy in which the addition of tolterodine resulted in prolonged international normalized ratios (INRs). Two patients, each receiving warfarin for stroke prophylaxis in association with chronic atrial fibrillation, developed adverse effects after the initiation of tolterodine for urinary disorders. Other medications for concurrent medical diagnoses had remained unchanged. One patient had an episode of prostatitis, which was treated with levofloxacin immediately prior to tolterodine initiation. The warfarin dosage had remained constant for many weeks in both patients prior to and during the tolterodine trials. In each patient, the initiation of tolterodine was associated with a significant increase in the patient's INR measured 10-14 days later. Thus, tolterodine was ineffective in both patients and was discontinued one to two days before the elevated INRs were determined during routine clinic visits. INRs determined approximately two weeks after tolterodine was discontinued were similar to those obtained during the period before the use of the drug; the warfarin dosage remained unchanged. Rechallenge with tolterodine was not attempted in either patient. Several aspects of the reported cases support the validity of a proposed drug interaction when tolterodine is initiated in a patient stabilized on warfarin therapy. The temporal association of the course of tolterodine with an elevated INR, the return to the previous warfarin dose-INR response relationship after tolterodine discontinuation, and the absence of other causes for the elevated INR were factors found in both patients. Possible mechanisms to explain the suggested drug interaction are explored. Until further data are available, clinicians should be vigilant for a possible drug interaction when tolterodine therapy is initiated in a patient maintained on warfarin therapy.",1999.0,0,1
42,10583026,Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.,N Brynne; C Svanström; A Aberg-Wistedt; B Hallén; L Bertilsson,"To investigate the change in disposition of tolterodine during coadministration of the potent cytochrome P450 2D6 (CYP2D6) inhibitor fluoxetine. Thirteen patients received tolterodine l-tartrate 2 mg twice daily for 2.5 days, followed by fluoxetine 20 mg once daily for 3 weeks and then concomitant administration for an additional 2.5 days. They were characterized as extensive metabolizers (EM1 with one functional CYP2D6 gene, EM2 with two functional genes) or poor metabolizers (PM). Nine patients, three EM2 and four EM1 and two PM, completed the trial. Following tolterodine administration, the area under the serum concentration-time curve (AUC) of tolterodine was 4.4-times and 30-times higher among EM1 and PM, respectively, compared with EM2. The AUC of the 5-hydroxymethyl metabolite (5-HM) was not quantifiable in PM. Fluoxetine significantly decreased (P<0.002) the oral clearance of tolterodine by 93% in EM2 and by 80% in EM1. The AUC of 5-HM increased in EM2 and decreased in EM1. However, the exposure to the active moiety (unbound tolterodine +5-HM) was not significantly increased in the two phenotypes. The subdivision of the EM group showed a 2.1-fold increase in active moiety in EM2 but the exposure was still similar to EM1 compared with before the interaction. The study suggests a difference in the pharmacokinetics of tolterodine and its 5-hydroxymethyl metabolite depending on the number of functional CYP2D6 genes. Fluoxetine significantly inhibited the hydroxylation of tolterodine. Despite the effect on the pharmacokinetics of tolterodine in extensive metabolizers, the clinical effect is expected to be within normal variation.",1999.0,1,1
43,10583027,Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity.,N Brynne; C Forslund; B Hallén; L L Gustafsson; L Bertilsson,"To investigate the pharmacokinetics and safety of tolterodine and tolterodine metabolites after single-and multiple-dose administration in the absence and presence of ketoconazole, an inhibitor of cytochrome P450 (CYP) 3A4, in healthy volunteers with deficient CYP2D6 activity, i.e. poor metabolisers of debrisoquine. Eight healthy volunteers received single oral doses (2 mg) of tolterodine l-tartrate. Following a wash-out period of about 3 months, six of the subjects participated in a multiple-dose (1 mg twice daily) phase of the study. Ketoconazole 200 mg was given once daily for 4-4.5 days during both the single and multiple dose tolterodine administration phases. Blood samples were drawn and the pharmacokinetics of tolterodine and its metabolites were determined. A decrease (P<0.01) in apparent oral clearance of tolterodine, from 10- 12 l h-1 to 4.3-4.7 l h-1, was obtained during concomitant administration of ketoconazole, yielding at least a two-fold increase in the area under the serum concentration-time curve after single as well as after multiple doses following single dose administration of tolterodine. The mean (+/-s.d.) terminal half-life increased by 50% from 9.7+/-2.7 h to 15+/-5.4 h in the presence of ketoconazole. CYP3A4 is the major enzyme involved in the elimination of tolterodine in individuals with deficient CYP2D6 activity (poor metabolisers), since oral clearance of tolterodine decreased by 60% during ketoconazole coadministration. This inhibition resulted in 2.1-fold increase in AUC.",1999.0,1,1
44,10610647,Update in women's health.,P Charney; J Walsh; A B Nattinger,,2000.0,0,0
45,10628907,Inhibitory effects of trospium chloride on cytochrome P450 enzymes in human liver microsomes.,S Beckmann-Knopp; S Rietbrock; R Weyhenmeyer; R H Böcker; K T Beckurts; W Lang; U Fuhr,"Trospium chloride, an atropine derivative used for the treatment of urge incontinence, was tested for inhibitory effects on human cytochrome P450 enzymes. Metabolic activities were determined in liver microsomes from two donors using the following selective substrates: dextromethorphan (CYP2D6), denitronifedipine (CYP3A4), caffeine (CYP1A2), chlorzoxazone (CYP2E1), S-(+)-mephenytoin (CYP2C19), S-(-)-warfarin (CYP2C9) and coumarin (CYP2A6). Incubations with each substrate were carried out without a possible inhibitor and in the presence of trospium chloride at varying concentrations (37-3000 microM) at 37 degrees in 0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by high-performance liquid chromatography (HPLC) in all cases except CYP2A6 where direct fluorescence spectroscopy was used. First, trospium chloride IC50 values were determined for each substrate at respective K(M) concentrations. Trospium chloride did not show relevant inhibitory effects on the metabolism of most substrates (IC50 values considerably higher than 1 mM). The only clear inhibition was seen for the CYP2D6-dependent high-affinity O-demethylation of dextromethorphan, where IC50 values of 27 microM and 44 microM were observed. Therefore, additional dextromethorphan concentrations (0.4-2000 microM) were tested. Trospium chloride was a competitive inhibitor of the reaction with Ki values of 20 and 51 microM, respectively. Thus, trospium chloride has negligible inhibitory effects on CYP3A4, CYP1A2, CYP2E1, CYP2C19, CYP2C9 and CYP2A6 activity but is a reasonably potent inhibitor of CYP2D6 in vitro. Compared to therapeutic trospium chloride peak plasma concentrations below 50 nM, the 1000-times higher competitive inhibition constant Ki however suggests that inhibition of CYP2D6 by trospium chloride is without any clinical relevance.",2000.0,0,0
46,10636496,Pregnancy outcomes in healthy nulliparas who developed hypertension. Calcium for Preeclampsia Prevention Study Group.,J C Hauth; M G Ewell; R J Levine; J R Esterlitz; B Sibai; L B Curet; P M Catalano; C D Morris,"To determine maternal and perinatal outcomes in nulliparas with pregnancy-associated hypertension or preeclampsia. We conducted (and reported elsewhere) a randomized, double-masked, placebo-controlled trial calcium supplementation of 4589 healthy nulliparas assigned at 13-21 weeks' gestation. This well-defined and characterized data set provided an opportunity to detail more precisely adverse maternal, fetal, and newborn outcomes in women who developed hypertension among a prospective series of healthy nulliparas. Of 4302 women observed to or beyond 20 weeks' gestation, 1073 (24.9%) developed mild or severe pregnancy-associated hypertension or preeclampsia. One hundred sixteen women of the 1073 with hypertension (10.8%) and 336 of the 3229 without hypertension (10.4%) were delivered before 37 weeks' gestation. Fetal and neonatal mortality were similar in those groups; however, selected maternal and newborn morbidities were significantly greater in women with hypertension. Significantly increased maternal morbidities included increased cesarean deliveries, abruptio placentae, and acute renal dysfunction; and significantly increased perinatal morbidities included respiratory distress syndrome, ventilatory support, and fetal growth restriction. Adverse outcomes were highest in women with severe pregnancy-associated hypertension or preeclampsia. Hypertension, especially severe hypertension, was associated with an appreciable increase in important maternal and perinatal morbidity but not perinatal mortality.",2000.0,1,1
47,10647975,A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis.,A K Gupta; N H Shear,"The newer antifungal agents itraconazole, terbinafine and fluconazole have become available to treat onychomycosis over the last 10 years. During this time period these agents have superseded griseofulvin as the agent of choice for onychomycosis. Unlike griseofulvin, the new agents have a broad spectrum of action that includes dermatophytes, Candida species and nondermatophyte moulds. Each of the 3 oral antifungal agents, terbinafine, itraconazole and fluconazole, is effective against dermatophytes with relatively fewer data being available for the treatment of Candida species and nondermatophyte moulds. Itraconazole is effective against Candida onychomycosis. Terbinafine may be more effective against C. parapsilosis compared with C. albicans; furthermore with Candida species a higher dose of terbinafine or a longer duration of therapy may be required compared with the regimen for dermatophytes. The least amount of experience in treating onychomycosis is with fluconazole. Griseofulvin is not effective against Candida species or the nondermatophyte moulds. The main use of griseo-fulvin currently is to treat tinea capitis. Ketoconazole may be used by some to treat tinea versicolor with the dosage regimens being short and requiring the use of only a few doses. The preferred regimens for the 3 oral antimycotic agents are as follows: itraconazole - pulse therapy with the drug being administered for 1 week with 3 weeks off treatment between successive pulses; terbinafine - continuous once daily therapy; and fluconazole - once weekly treatment. The regimen for the treatment of dermatophyte onychomycosis is: itraconazole - 200mg twice daily for I week per month x 3 pulses; terbinafine - 250 mg/day for 12 weeks; or, fluconazole - 150 mg/wk until the abnormal-appearing nail plate has grown out, typically over a period of 9 to 18 months. For the 3 oral antifungal agents the more common adverse reactions pertain to the following systems, gastrointestinal (for example, nausea, gastrointestinal distress, diarrhoea, abdominal pain), cutaneous eruption, and CNS (for example, headache and malaise). Each of the new antifungal agents is more cost-effective than griseofulvin for the treatment of onychomycosis and is associated with high compliance, in part because of the shorter duration of therapy. The newer antifungal agents are generally well tolerated with drug interactions that are usually predictable.",2000.0,0,0
48,10691817,"Oxybutynin for detrusor instability with adjuvant salivary stimulant pastilles to improve compliance: results of a multicentre, randomized controlled trial.",D G Tincello; E J Adams; J R Sutherst; D H Richmond,"To test the hypothesis that compliance with oxybutynin would be improved if the severity of dry mouth could be reduced, thus leading to improved urinary symptom response and improved outcome, in a randomized, controlled trial of oxybutynin with or without salivary stimulant pastilles in patients with detrusor instability. Sixty-seven women with detrusor instability were randomized to a variable dose regimen of oxybutynin with (37) or without (30) salivary stimulant pastilles for 8 weeks. Patients were asked to complete a baseline voiding diary. In weeks 1 and 2, patients were encouraged to adjust the dose of oxybutynin themselves to achieve optimum symptomatic control. A second diary was completed in the sixth week and patients were reviewed at 8 weeks. The outcome measures were the compliance rate, follow-up attendance rate, maximum dose of medication, changes in voiding and incontinence episodes, and changes in severity of urgency and of dry mouth symptoms between the first and sixth week. Of the 67 women, 32 (47%) completed the study; the proportion completing was the same in both groups. Four patients had stopped the medication and there was no difference in the distribution of maximum dosage achieved between the groups. Both groups reported a reduced severity of urgency symptoms and increased severity of dry mouth. There were no differences in reported symptom change between the groups during the study. The combination of oxybutynin and salivary stimulant pastilles does not improve compliance or symptom relief compared with oxybutynin alone; it does not allow a greater dose of oxybutynin to be tolerated.",2000.0,0,0
49,10699610,Combined intravesical and oral oxybutynin chloride in adult patients with spinal cord injury.,J Pannek; H J Sommerfeld; U Bötel; T Senge,"Detrusor hyperreflexia with elevated storage pressures presents a major risk factor for renal damage in patients with neurogenic lower urinary tract dysfunction. If standard anticholinergic treatment is unsuccessful, surgical treatment must be considered. We evaluated the effects of intravesical oxybutynin treatment on detrusor hyperreflexia in patients in whom standard oral treatment had failed. Twenty-five patients (mean age 36. 7 years) with storage pressures greater than 40 cm H(2)O despite standard anticholinergic treatment received intravesical (15 mg three times daily) and oral oxybutynin chloride treatment. The follow-up evaluations included urodynamic testing, renal ultrasound, urine examination (urinalysis and urine culture), and evaluation of side effects. The mean follow-up was 6 months. Intravesical treatment led to an increase in bladder storage volume from 349 to 420 mL. The mean maximum storage pressure was significantly reduced from 54 to 26.5 cm H(2)O. Detrusor storage pressures returned to values less than 40 cm H(2)O in 21 of 25 patients. Dysreflexia was treated successfully in 3 of 5 patients. No patient developed renal damage. No severe side effects or drug-related discontinuation of treatment were observed. Intravesical oxybutynin therapy seems to be a safe and effective treatment option for detrusor hyperreflexia in adults and avoids surgical treatment in most patients. Long-term observations concerning side effects, acceptance, and efficacy are needed.",2000.0,0,0
50,10699623,Efficacy and tolerability of tolterodine in children with detrusor hyperreflexia.,C Goessl; T Sauter; T Michael; B Bergé; M Staehler; K Miller,"To investigate the urodynamic effects and tolerability of the new antimuscarinic drug tolterodine in children with detrusor hyperreflexia. Twenty-two children (12 boys and 10 girls; age range 3 months to 15 years, mean age 5.7 years) with detrusor hyperreflexia resulting in maximum detrusor pressures exceeding 40 cm H(2)O during filling cystotonometry were enrolled to receive tolterodine tartrate (a total of 0.1 mg/kg orally daily, divided into two doses) either as a first-line therapy (n = 12, group 1) or replacing oxybutynin chloride therapy (n = 10, group 2). Within 3 months, all patients underwent urodynamic re-evaluation during ongoing tolterodine treatment. In group 1, the mean maximum bladder capacity increased from 120.2 to 173.0 mL (+44%), the mean detrusor compliance increased from 8.7 to 13.5 mL/cm H(2)O (+55%), and the mean maximum detrusor pressures decreased from 70.1 to 37.9 cm H(2)O (-46%); the differences were significant (P < 0.001). In group 2, no differences in the urodynamic effects of oxybutynin versus tolterodine were noted. Only 1 patient experienced a transient and moderately adverse effect with tolterodine. Although based on a limited number of subjects, these data indicate that in pediatric patients with detrusor hyperreflexia, tolterodine may be better tolerated than and equally effective as the standard drug oxybutynin chloride.",2000.0,0,0
51,10703502,,,,,0,1
52,10735579,Intravesical neuromodulatory drugs: capsaicin and resiniferatoxin to treat the overactive bladder.,D Y Kim; M B Chancellor,"Current pharmacologic treatment of the overactive bladder relies on anticholinergic drugs. However, these drugs often have troublesome side effects and frequently are given in doses insufficient to restore continence in patients with detrusor instability. We present the background and basic and clinical research dealing with intravesical instillation of capsaicin and resinfferatoxin as treatments for the overactive bladder. Capsaicin is the main pungent ingredient in ""hot"" peppers of the genus Capsicum. It is a specific neurotoxin that desensitizes C-fiber afferent neurons, which may be responsible for the signals that trigger detrusor overactivity. Studies with capsaicin over the past 8 years have demonstrated clinical efficacy with minimal long-term complications. Most of these studies have also shown that the acute pain and irritation associated with capsaicin are a major deterrent to widespread use. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin that appears to have similar efficacy but with much less acute side effects may be more useful. Intravesical instillation of capsaicin or resiniferatoxin is a promising treatment for the overactive bladder.",2000.0,0,0
53,10755330,Extended-release oxybutynin.,A M Comer; K L Goa,"Extended-release oxybutynin (Ditropan XL) uses an osmotic system (OROS) to deliver a controlled amount of oxybutynin chloride into the gastrointestinal tract over a 24-hour period when taken once daily. Oxybutynin binds to M3 muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. Mean peak plasma concentrations are lower with extended-release oxybutynin 15mg once daily than with conventional immediate-release oxybutynin 5mg taken 3 times daily. Relative bioavailabilities of parent drug and metabolite N-desethoxybutynin are 153 and 69%, respectively, for extended-release oxybutynin when compared with immediate-release oxybutynin. In short (< or =6 weeks) randomised, double-blind clinical trials of patients with detrusor instability, extended-release oxybutynin 5 to 30mg once daily significantly reduced the mean weekly number of urge incontinence episodes by 84 to 90%. Extended-release oxybutynin had similar efficacy to immediate-release oxybutynin. Adverse events reported by patients taking extended-release oxybutynin were dose-related anticholinergic effects, most frequently dry mouth, somnolence, constipation, blurred vision and dizziness. A large noncomparative study demonstrated that approximately two thirds of the patients prescribed extended-release oxybutynin for detrusor instability were still taking the medication 6 months later.",2000.0,0,0
54,10759661,"Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial.",L Cardozo; C R Chapple; P Toozs-Hobson; M Grosse-Freese; M Bulitta; W Lehmacher; W Strösser; B Ballering-Brühl; M Schäfer,"To assess the efficacy and safety of trospium chloride (TCl, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo. In all, 208 patients were allocated at random to either TCl or placebo in a double-blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy. Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 mL, mean 37.3 mL, one-sided P = 0. 0054) and urinary volume at first unstable contraction (median treatment effect 45.0 mL, mean 63.6 mL, one-sided P = 0.0015). The patients' assessment of efficacy showed significantly greater clinical improvement in the TCl group than in the placebo group (two-sided P = 0.0047). Furthermore, TCl was well tolerated, with similar frequencies of adverse events reported in both groups (68% in the TCl and 62% in the placebo group). Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.",2000.0,1,1
55,10767443,Nonpharmacologic treatments for overactive bladder-pelvic floor exercises.,K Bø; L C Berghmans,"The theory behind the use of physical therapies (electrical stimulation or pelvic floor muscle [PFM] training with or without biofeedback) for overactive bladder is to (1) inhibit detrusor muscle contraction by voluntary contraction of the PFMs at the same time as the urge to void; and (2) prevent sudden falls in urethral pressure by a change in PFM morphology, position, and neuromuscular function. Few trials have evaluated the effect of PFM training on symptoms of overactive bladder. Most studies are flawed because they include several diagnoses and treatment modalities in the same intervention. Because of the lack of evidence, no firm conclusion can be drawn on the effect of PFM exercise on overactive bladder. There are some initially promising results, but there is still a need for high-quality, randomized controlled trials on the effect of PFM training on the inhibition of detrusor contraction in human beings. The efficacy of PFM training in combination with other treatments, such as pharmacotherapy, also requires investigation.",2000.0,0,0
56,10767450,Muscarinic receptor antagonists in the treatment of overactive bladder.,C R Chapple,"A wealth of clinical evidence supports the view that muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M(3) receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated.",2000.0,0,0
57,10767457,Discussion: resiniferatoxin-preliminary data.,M B Chancellor,,2000.0,0,0
58,10772377,Immediate-release oxybutynin versus tolterodine in detrusor overactivity: a population analysis.,M Lawrence; D R Guay; S R Benson; M J Anderson,"We evaluated adherence to treatment with immediate-release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11-1.15 and 0.07-1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one-third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.",2000.0,1,1
59,10775736,Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group.,E Versi; R Appell; D Mobley; W Patton; D Saltzstein,"To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth. Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose. Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin. At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group.",2000.0,1,1
60,10792154,A randomized controlled trial comparing the efficacy of controlled-release oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilized on 5 mg twice daily of oxybutynin.,J Birns; E Lukkari; J G Malone-Lee,"To compare the efficacy of a controlled-release (CR) formulation of oxybutynin with that of conventional oxybutynin in patients with detrusor instability or detrusor hyper-reflexia whose symptoms were stabilized on conventional oral oxybutynin tablets. The study comprised a randomized, double-blind, parallel-group trial involving 130 patients drawn from 15 centres in the UK. The study was of 6 weeks' duration, i.e. 2 weeks of screening whilst taking conventional oxybutynin tablets (5 mg twice daily) followed by 4 weeks of double-blind treatment with either CR oxybutynin tablets (10 mg once daily) or conventional oxybutynin tablets (5 mg twice daily). Outcome measures were changes in 24-h frequency and 24-h incontinence episodes recorded throughout the study on diary charts. Adverse events were recorded by patients in their diary charts and serum concentrations of oxybutynin and its active metabolite, N-desethyloxybutynin, were measured at baseline and at completion of the study to detect possible drug accumulation. The treatments did not differ significantly in any of the outcome measures. The primary efficacy criterion was the daytime continence at completion of the study; 53% and 58% of patients were continent on CR and conventional oxybutynin treatments, respectively (the 95% confidence interval of the difference in the proportion being - 22% to 13%; P = 0.62). The total number of side-effects experienced by those patients receiving treatment with the CR formulation was 57% of that for patients receiving treatment with conventional oxybutynin. Individual side-effects showed a similar distribution within treatment groups. There was no evidence of the accumulation of oxybutynin or N-desethyloxybutynin during the multiple dosing of CR or conventional oxybutynin tablets. The CR and conventional formulations of oxybutynin did not differ in their efficacy, and the CR formulation was associated with fewer side-effects. In addition, CR oxybutynin appeared to maintain therapeutic blood levels over the 24 h dosing interval with no accumulation of oxybutynin or its active metabolite. Once-daily dosing with a CR tablet is seen as convenient for the patient and is expected to result in improved compliance in patients already stabilized on conventional oxybutynin treatment.",2000.0,1,1
61,10798461,Combined behavioral and drug therapy for urge incontinence in older women.,K L Burgio; J L Locher; P S Goode,"The purpose of this study was to examine the effects of combining behavioral treatment and drug treatment for urge incontinence in community-dwelling older women. Modified crossover design (extension of a randomized clinical trial). Eligible subjects were stratified according to type and severity of incontinence and randomized to behavioral treatment, drug treatment, or a control condition (placebo). Subjects not totally continent or not satisfied after 8 weeks of a single treatment were offered the opportunity to cross over into combined therapy. A university-based outpatient geriatric medicine clinic. Subjects in the clinical trial were 197 ambulatory, nondemented, community-dwelling women (age 55 years or older) with persistent urge urinary incontinence. Thirty-five subjects participated in combined treatment. One group of subjects received four sessions (over 8 weeks) of biofeedback-assisted behavioral training followed by 8 weeks of behavioral training combined with drug therapy (oxybutynin chloride individually titrated from 2.5 mg to 15 mg daily). The second group received drug therapy first, followed by 8 weeks of drug therapy combined with behavioral training. Bladder diaries completed by subjects before and after each treatment phase were used to calculate change in the frequency of incontinent episodes. Eight subjects (12.7%) crossed from behavioral treatment alone to combined behavioral and drug therapy. Additional benefit was seen in improvement from a mean 57.5% reduction of incontinence with single therapy to a mean 88.5% reduction of incontinence with combined therapy (P = .034). Twenty-seven subjects (41.5%) crossed from drug therapy alone to combined drug and behavioral treatment. They also showed additional improvement, from a mean 72.7% reduction of incontinence with single therapy to a mean 84.3% reduction of incontinence with combined therapy (P = .001). This study shows that combining drug and behavioral therapy in a stepped program can produce added benefit for patients with urge incontinence.",2000.0,0,0
62,10799190,Interstitial cystitis: bladder training with intravesical oxybutynin.,G A Barbalias; E N Liatsikos; A Athanasopoulos; G Nikiforidis,"We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis. The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis. Patients were treated with gradual intravesical instillation of saline oxybutynin solution (oxybutynin group) or gradual filling of simple saline (control group). Evaluation parameters consisted of symptom problem index, voids per day, volume per void, functional bladder capacity, volume at first sensation, cystometric bladder capacity and cystometric volume at first sensation. Statistically significant improvement of all evaluated parameters was found in both groups. When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group. Bladder training alone produces a satisfactory result by gradually expanding the bladder, and an additional statistically significant improvement is evident with intravesical oxybutynin.",2000.0,0,0
63,10824450,[Assessment of effectiveness of and tolerance to oxybutynin in the treatment of unstable bladder in women].,E A Serrano Brambila; R G Quiroga Avila; J L Lorenzo Monterrubio; J Moreno Aranda,"Unstable bladder is a frequent syndrome in women and is due in the most part because of detrusor involuntary contractions, mainly due to detrusor denervation, which produces voiding hypersensitivity and loss of cortical inhibition control, clinical manifestations are: frequency, nicturia, urgency and urge incontinence. Historically the most effective treatment has been muscular relaxing agents and anticholinergic agents. We present a prospective, double blind, cross, placebo control study to evaluate efficacy and tolerance of oxybutynin in women with unstable bladder. We included 44 adult women with unstable bladder, 22 unitially received oxybutynin 5 mg t.i.d. and 22 placebo 5 mg t.i.d. aleatory in both groups through 6 weeks, later wash-out period was performed and those women in which initially received oxybutynin were administered placebo and those women in which initially received placebo, were administered oxybutynin, for another six weeks. Five patients which initiated the study with oxybutynin abandoned the study, 2 of them for intolerance and 3 for unknown causes. Two women in which initially received placebo abandoned follow-up too. A total of 74 subjects (37 for each branch of study) had an age average of 51.7. Symptoms scoring decreased from 13 to 11 and 6 points with placebo and oxybutynin respectively (p = 0.001). The analog visual scale of symptoms decreased from 77% to 62.5% and 40% with placebo and oxybutynin respectively (p = 0.003). The overall rate of improvement evaluated through symptoms scoring was from 27% with placebo and 72.9% with oxybutynin (p = 0.000) and evaluated through analog visual scale of symptoms was from 40% with placebo and 78.3% with oxybutynin (p = 0.002). The vesical volume at first voiding sensation increased from 129 ml to 134 ml and 187 ml with placebo and oxybutynin respectively (p = 0.021) and the maximum cystometric capacity increased from 231 ml to 236 ml and 301 ml with placebo and oxybutynin respectively. The most frequent adverse effect in both groups was mouth dryness and it presented in 7 (19%) and 34 (91%) patients with placebo and oxybutynin respectively (p = 0.000). Only 5 of 44 patients (11.3%) with oxybutynin and 2 of 44 patients (4.4%) with placebo abandoned follow up (p = 0.14). We concluded that oxybutynin improve significantly the unstable bladder symptoms in women, possibly by increasing functional bladder capacity and decreasing voiding sensitivity, with good tolerance of mouth dryness in the majority of patients.",2000.0,0,0
64,10828671,"Efficacy and cardiac safety of propiverine in elderly patients - a double-blind, placebo-controlled clinical study.",W Dorschner; J U Stolzenburg; R Griebenow; M Halaska; G Schubert; G Mürtz; M Frank; F Wieners,"The study investigated the efficacy and cardiac safety of propiverine in the elderly, because the induction of life-threatening ventricular arrhythmia has been reported for some drugs prescribed in the therapy of urinary incontinence. Ninety-eight patients (21 male, 77 female; 67.7+/-6.3 years of age) suffering from urgency, urge incontinence or mixed urge-stress incontinence were included in the double-blind, multicentre, placebo-controlled, randomized study. After a 2-week placebo run-in period, the patients received propiverine (15 mg t.i.d.) or placebo (t.i.d.) for 4 weeks. Before (V1, V2) and during the treatment period (V3, V4), standard ECGs and 24-hour long-term ECGs were recorded. Propiverine caused a significant reduction of the micturition frequency (V2: 8.7+/-4.2, V4: 6.5+/-3.2 ml; p< or =0.01), reflected in a significant increase in the average micturition volume (V2: 163.5+/-65.9, V4: 216.3+/-101.5 ml; p< or =0.01) and a significant decrease in episodes of incontinence (-54%; p = 0.048). These findings were confirmed by the overall assessment at V4, in which approximately 90% of patients under propiverine either had no urge incontinence or urge symptoms, or showed improvement. Resting and ambulatory electrocardiograms indicated no significant changes. Neither the frequency-corrected Q-T interval nor other cardiac parameters were relevantly altered. The frequency of cardiac events (Lown classes IVa/b) was random, revealing no difference between placebo and propiverine. The incidence of adverse events was very low (2% dryness of the mouth under propiverine) and confirmed by the findings from the quality of life questionnaires. A favourable benefit-risk ratio without the induction of any cardiac arrhythmia in the treatment of elderly patients suffering from urgency, urge incontinence or combined urge-stress incontinence is therefore proven for propiverine.",2000.0,0,0
65,10839552,,,,,0,0
66,10840082,Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury.,M L Sipski; R C Rosen; C J Alexander; R M Hamer,"Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting. Nineteen premenopausal women with SCIs were randomly assigned to receive either sildenafil (50 mg) or placebo in a double-blind, crossover design study. Physiologic and subjective measures of sexual response, heart rate, and blood pressure were recorded during baseline and sexual stimulation conditions. Adverse events were also recorded. Significant increases in subjective arousal (SA) were observed with both drug (P <0.01) and sexual stimulation conditions (P <0.001), and a borderline significant (P <0.07) effect of drug administration on vaginal pulse amplitude (VPA) was noted. Maximal responses occurred when sildenafil was combined with visual and manual sexual stimulation. Cardiovascular data showed modest increases in heart rate (+/-5 bpm) and mild decreases in blood pressure (+/-4 mm Hg) across all stimulation conditions, consistent with the peripheral vasodilatory mechanism of the drug. Sildenafil was well tolerated with no evidence of significant adverse events. Findings suggest that sildenafil may partially reverse the sexual dysfunction commonly associated with SCI in women. Consistent with previous findings in men, the sexual effects of the drug were most evident under conditions of optimal stimulation. Mild, clinically insignificant cardiovascular effects were also noted. Further large-scale studies of sildenafil's effects in women with neurogenic sexual dysfunction are strongly indicated.",2000.0,0,0
67,10852094,Urinary incontinence.,J A Couture; L Valiquette,"One of the more prevalent conditions associated with aging is urinary incontinence (UI), which may affect up to 55% of women and 34% of men older than 65 years. As a result of increasing longevity in developed nations, the proportion of UI-susceptible individuals continues to grow, presenting clinical and economic challenges to healthcare providers. To assist the clinician in making informed decisions regarding UI, provide information on the wider ramifications of the disease, and provide a comprehensive overview of the condition. MEDLINE (1966-December 1998) was searched for relevant publications using the following search terms: UI, UI in the elderly, treatment of UI, oxybutynin, flavoxate, vasopressin, quality of life in UI, and economic impact of UI. Key articles relating to the etiology, diagnosis, classification, economic burden, quality of life, and treatment of UI were retrieved, and this information formed the basis of the review. Although UI can be controlled relatively well with existing therapies, only about 50% of affected patients may actually seek care. There are a variety of therapeutic options available for the treatment of UI, although pharmacologic intervention is presently a relatively minor component of overall care; this suggests that effective drug therapy might play a more significant role in the future. The economic burden associated with the care of the incontinent patient is substantial, and in the US the direct medical cost of the disease was estimated at $25.5 billion in 1995. The disease also has a large impact on the individual UI patient, negatively affecting many parameters normally associated with a tolerable health-related quality of life.",2000.0,0,0
68,10858873,Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder.,S Uckert; C G Stief; K P Odenthal; M C Truss; B Lietz; U Jonas,"The spasmolytic activity of flavoxate (CAS 15301-69-6) and the anticholinergic agents oxybutynin (CAS 5633-20-5), tolterodine (CAS 124937-51-5) and trospium chloride (CAS 10405-02-4), all of which are commonly utilized in the treatment of urinary incontinence, on muscarinic tension and electrically evoked contractions of isolated human detrusor smooth muscle strips was studied using the organ bath technique. Within the concentration ranges tested (trospium chloride 10(-11)-10(-6) mol/l, flavoxate and oxybutynin 10(-9)-10(-5) mol/l, tolterodine 10(-10)-10(-5) mol/l), each drug caused a concentration-dependent relaxation of the tension elicited by muscarinic stimulation and dose-dependently attenuated the contractions induced by electrical field stimulation (EFS). The effects of trospium chloride and tolterodine on carbachol-induced muscarinic tension were more pronounced than those of oxybutynin, while trospium chloride and oxybutynin were most effective in inhibiting the contractions induced by EFS. Flavoxate was significantly less effective than all other drugs tested. Regardless the individual drug concentrations needed for maximal efficacy, the potency of oxybutynin and flavoxate to reverse muscarinic tension and attenuate EFS-evoked contractions was almost comparable while tolterodine and trospium chloride were more effective in relaxing the muscarinic tension of the detrusor strip preparations than causing inhibition of EFS-induced contractions. Our results again underline the ratio for the use of nortropane analogues (trospium chloride) and phenylpropylamine cresols (tolterodine) in the treatment of frequency, urgency and urge incontinence secondary to an overactive bladder.",2000.0,0,0
69,10860131,Selective prescribing of spasmolytics.,K L Movig; A C Egberts; A W Lenderink; H G Leufkens,"Daily clinical practice often differs largely from the clinical trial setting, so extrapolation of outcomes from trial data, such as safety, effectiveness, and economic outcomes, can be deceptive. Prescribers may intend to treat a selected group of patients with new drugs; this practice could result in significant bias in assessing outcomes of these agents during their use in daily clinical practice. To evaluate what type of patient received tolterodine compared with the spasmolytic drugs previously marketed (oxybutynin, flavoxate, emepronium). An observational, follow-up study. Eighteen collaborating community pharmacies. Aged > or = 18 years, noninstitutionalized; initial therapy with tolterodine, oxybutynin, flavoxate, or emepronium. Tolterodine was often used as a second-line and even as a third-line treatment, and was prescribed to a ""polluted"" population in terms of concomitant psychotropic medication. Tolterodine users were 7.5 times more likely to have received another spasmolytic drug (RR 7.5, 95% CI 4.8 to 11.9). In addition, these patients more frequently used antiparkinsonian drugs (RR 4.1, 95% CI 1.6 to 10.4) as well as antipsychotic drugs (RR 2.9, 95% CI 1.4 to 6.2). There was a small difference in concomitant use of antidepressants and benzodiazepines between patients receiving tolterodine versus those taking other spasmolytic drugs. Tolterodine is prescribed for a population differing from that receiving previously marketed spasmolytic drugs. Selective prescribing should recognized when evaluating new drugs in daily clinical practice. Policy makers, such as pharmacy and therapeutics committees, should consider this aspect in their formulary decisions since selective prescribing can lead to unjustified conclusions about a drug's therapeutic effects (e.g., efficacy, safety, cost-effectiveness).",2000.0,0,0
70,10888308,Propiverine-induced Parkinsonism: a case report and a pharmacokinetic/pharmacodynamic study in mice.,H Matsuo; A Matsui; R Nasu; H Takanaga; N Inoue; F Hattori; H Ohtani; Y Sawada,"We present a case report of propiverine-induced Parkinsonism. We previously reported the induction of catalepsy by amiodarone, aprindine and procaine, which possess a diethylaminomethyl moiety and demonstrated selective blockade of dopamine D2 receptors by these drugs in mice. We hypothesized that drugs possessing a diethylaminomethyl structure may generally induce Parkinsonism and/or catalepsy. Thus, we performed a study to examine whether oxybutynin, pentoxyverine and etafenone, as well as propiverine, induce catalepsy in mice. The intensity of drug-induced catalepsy was in the order: haloperidol > etafenone > pentoxyverine > propiverine > oxybutynin. In vivo occupancy of dopamine D1, D2 and mACh receptors in the striatum was also examined. The in vitro binding affinities to the D1, D2 and mACh receptors in the striatum synaptic membrane were within the ranges of 2.4-140 microM, 380-4,200 nM, and 1.2-2,800 nM, respectively. These results support the idea that any drug possessing a diethylaminomethyl moiety may contribute to the induction of catalepsy, possibly by occupying dopamine receptors.",2001.0,0,0
71,10894308,Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group.,J S Brown; E Vittinghoff; J F Wyman; K L Stone; M C Nevitt; K E Ensrud; D Grady,"To determine if urge urinary incontinence is associated with risk of falls and non-spine fractures in older women. Type and frequency of incontinent episodes were assessed by 6,049 community-dwelling women using a self-completed questionnaire. Postcards were subsequently mailed every 4 months to inquire about falls and fractures. Incident fractures were confirmed by radiographic report. Logistic and proportional hazard models were used to assess the independent association of urge urinary incontinence and risk of falling or fracture. The mean age of the women was 78.5 (+/- 4.6) years. During an average follow-up of 3 years, 55% of women reported falling, and 8.5% reported fractures. One-quarter of the women (1,493) reported weekly or more frequent urge incontinence, 19% (1,137) reported weekly or more frequent stress incontinence, and 708 (12%) reported both types of incontinence. In multivariate models, weekly or more frequent urge incontinence was associated independently with risk of falling (odds ratio = 1.26; 95% confidence interval (CI), 1.14-1.40) and with non-spine nontraumatic fracture (relative hazard 1.34; 95% CI, 1.06-1.69; P = .02). Stress incontinence was not associated independently with falls or fracture. Weekly or more frequent urge incontinence was associated independently with an increased risk of falls and non-spine, nontraumatic fractures in older women. Urinary frequency, nocturia, and rushing to the bathroom to avoid urge incontinent episodes most likely increase the risk of falling, which then results in fractures. Early diagnosis and appropriate treatment of urge incontinence may decrease the risk of fracture.",2000.0,0,0
72,10924511,,,,,0,0
73,10924932,"Possible site of action of TAK-637, a tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs.",I Kamo; S Imai; S Okanishi; T Doi,"TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the micturition reflex in guinea pigs. The aim of this study was to clarify its mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical reflex induced by electrical stimulation of the proximal cut end of the pelvic nerve in spinal animals, but not bladder contractions induced by electrical stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no effect on carbachol- or electrical field stimulation-induced contractions of isolated bladder muscle strips in an organ bath, whereas drugs used for abnormally frequent micturition inhibited both contractions. These results suggest that TAK-637 inhibits the micturition reflex by acting, at least in part, on the spinal cord, and its mechanism of action clearly differs from those of antimuscarinics or spasmolytics.",2000.0,0,0
74,11054030,Combination therapy of imipramine with oxybutynin in children with enuresis nocturna.,L Tahmaz; Y Kibar; I Yildirim; S Ceylan; M Dayanç,"The treatment approach for enuresis is controversial due to the lack of consensus as to the exact causes of nocturnal enuresis. Despite various treatment modalities, pharmacotherapy still appears to be the common choice. The aim of this prospective study was the evaluation of the efficacy of combination therapy (imipramine and oxybutynin) in patients with enuresis nocturna. This prospective study was done with 77 monosymptomatic nocturnal enuretics between July 1996 and December 1998. Even though there is no statistically significant difference between combination therapy (imipramine plus oxybutynin) and monotherapy, clinical data showed that combination therapy is more effective. We conclude that combination of imipramine with oxybutynin is a safe and new choice in the treatment of nocturnal enuresis.",2001.0,0,0
75,11069384,Comparison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle.,M Yono; M Yoshida; W Takahashi; A Inadome; S Ueda,"To evaluate the effects of tolterodine, vamicamide and temiverine, novel antimuscarinic drugs developed for the treatment of frequency and urinary incontinence, on human detrusor smooth muscle. Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. Using an organ-bath technique, the effects of various drugs on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in the detrusor strips were investigated. Carbachol (0.001-10000 micromol/L) caused concentration-dependent contractions in human detrusor smooth muscles. Tolterodine (0.01-10 micromol/L), vamicamide (0.01-10 micromol/L), temiverine (0.01-1 micromol/L) and atropine (0.001-1 micromol/L) caused parallel shifts to the right of the concentration-response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA2 values was atropine = tolterodine > vamicamide > temiverine. Tolterodine, vamicamide and atropine did not inhibit the maximum contractile responses to carbachol, while temiverine (10 micromol/L) significantly inhibited the maximum contractions. Tolterodine (0.001-1 micromol/L) and vamicamide (0.01-10 micromol/L) did not inhibit the KCl- (80 mmol/L) and CaCl2-induced (5 mmol/L) contractions, while temiverine (0.01-10 micromol/L) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contractions in human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 1 micromol/L atropine, tolterodine and vamicamide did not inhibit the contractions induced by electrical field stimulation at all frequencies, while temiverine (10 micromol/L) significantly inhibited the contractions. Tolterodine and vamicamide inhibited contractions of human detrusor smooth muscles only through their antimuscarinic action, while temiverine had both antimuscarinic and calcium-antagonist actions. Furthermore, these novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.",2001.0,0,0
76,11090517,Regular review: management of urinary incontinence in women.,R Thakar; S Stanton,,2001.0,0,0
77,11099286,Recent advances: urology.,P Abrams; A Wein,,2001.0,0,0
78,11113737,Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group.,E Rovner; K J Propert; C Brensinger; A J Wein; M Foy; A Kirkemo; J R Landis; J W Kusek; L M Nyberg,"To evaluate the frequency and types of treatments reported at baseline in women who entered the Interstitial Cystitis Data Base (ICDB) cohort study. From 1993 to 1997, 581 women were enrolled and followed in the ICDB. All treatments reported at study entry, including those prescribed for interstitial cystitis (IC) and concomitant medications, were reviewed. The number and types of treatments were evaluated with respect to baseline factors such as prior diagnosis of IC and symptom severity. One hundred five (18%) women were receiving no therapy at baseline. Single-mode therapy was reported by 195 (34%) women, and a combination of two treatments was reported by 119 (21%) women. Three or more treatments were reported in 162 (28%) women. A total of 183 different types of therapies were recorded. The five most commonly used therapies for IC symptoms were cystoscopy and hydrodistention, amitriptyline, phenazopyridine, special diet, and intravesical heparin. Because most patients entered the ICDB before the approval of oral pentosan polysulfate sodium (PPS), only 6% of women reported oral PPS use at baseline. There were statistically significant associations between the number and types of treatments and clinical center, a prior diagnosis of IC, and symptom severity. The diversity of IC therapies underscores the lack of understanding about the treatment of this syndrome. Further research in IC is essential to develop and to evaluate rational therapies and treatment algorithms. These algorithms should be ""evidence based"" and should be revised as the underlying etiology and pathophysiology of IC is delineated.",2001.0,0,0
79,11114562,Advancements in pharmacologic management of the overactive bladder.,R R Dmochowski; R A Appell,"Continued developments in the understanding of lower urinary tract function have led to improvements in the pharmacologic manipulation of bladder dysfunction. Drug delivery changes have produced drugs that provide better efficacy and tolerability, thus improving patient compliance. Improvements in drug delivery systems have altered drug bioavailability and pharmacokinetics. Active current investigation in new agents and delivery systems for intravesical delivery has yielded intriguing early results that may substantially add to the armamentarium for the management of the overactive bladder (urgency, frequency, urge incontinence). New developments in the understanding of the neuropharmacology of the bladder, peripheral pelvic nerves, and sacral cord may provide agents with entirely new drug effects, either as primary agents or agents to be used in combination with currently available drugs. We herein review newer agents and drug delivery systems.",2001.0,0,0
80,11116281,Pharmacological agents for the treatment of urinary incontinence due to overactive bladder.,A J Wein,"Although the exact aetiology of overactive bladder is unknown to date, pharmacological therapy has been targeted to both the central and peripheral nervous systems. Potential CNS targets include GABA, opioid, serotonin (5-HT), dopamine and glutaminergic receptors as well as the alpha-adrenoceptors. Potential PNS targets include muscarinic receptors, calcium and potassium channels and alpha- and beta-adrenergic receptors. Since acetylcholine is the primary excitatory neurotransmitter involved in bladder (detrusor) contraction and emptying, anticholinergic agents are the primary compounds used clinically to decrease involuntary detrusor contractions. Anticholinergic therapy has a stabilising effect on the bladder (detrusor muscle); increases bladder capacity; decreases frequency of involuntary detrusor contractions; and delays the initial urge to void, but does not affect warning time. However, the clinical utility of antimuscarinic therapy is limited by the lack of receptor selectivity, resulting in the classic anticholinergic side effects of dry mouth, blurred vision, constipation and potentially, CNS effects such as somnolence and impaired cognitive function. These unwanted side effects often result in premature discontinuation of therapy and poor compliance. Previous attempts to develop uroselective alpha-adrenergic receptor antagonists have not been successful and although research continues, the hope that this class of agents would be viable alternatives to the anticholinergics remains to be proven in the clinical setting. The recent demise of several potassium channel openers does not augur well for the future of this class of agent. The reasons for the discontinuation of trials with these agents have not been fully elucidated, but one must assume that they were not uroselective and the cardiovascular side effects rendered them less than useful clinically. The serotonin re-uptake inhibitors appear to be promising novel therapeutic agents aimed at controlling bladder over-activity through specific CNS pathways. The sensory side of the micturition reflex is a potential therapeutic target. Agents to desensitise afferent nerve endings involved in C-fibre afferent reflexes include capsaicin and resiniferatoxin. Their clinical applicability is currently being evaluated. Finally, the recent findings related to the role of the P2X3 receptor in the sensory aspects of bladder filling have created new interest in the future development of agents that will improve the management of this prevalent and debilitating condition.",2001.0,0,0
81,11117074,Treatment of elderly women with urge incontinence in middle tennessee: a single institution practice-based study.,D J Grossklaus; J J Franke,"Urinary urge incontinence (UUI) is a major factor in reducing quality of life in elderly women. The treatment of UUI in the elderly population is complicated by comorbidities, polypharmacy, cost, and side effects. The purpose of this study was to examine our practice pattern in Middle Tennessee for the treatment of elderly women with UUI. We retrospectively reviewed the medical records of all women over age 65 seen at our institution between January 1, 1998 and September 1, 1999 with an initial complaint of pure UUI. Diagnosis was based on history and physical examination by a single urologist (JJF). Initial treatment in all patients was medication as well as timed and double voids. Medication chosen was based on cost factors, co-morbidities, current medications, and outcome from previous treatment. Of 53 women ranging in age from 65-87 years of age (avg. 74.7) included in this study, 6/53 (11.3%) had a previous CVA, and 2/53 (3.7%) had grade I-II cystoceles. Initial pharmacologic treatment included anticholinergic medication in 47 patients (88.6%), and either imipramine or topical estrogen alone in the remaining 11.4%. Of the anticholinergics, hyoscyamine time capsules were used in 29, tolterodine in 7, standard oxybutynin in 5, oxybutynin XL in 1, and a combination with imipramine in 5. Thirty-four of the 53 total patients (64.1%) discontinued their medications because of no improvement 14 (41.1%), dry mouth 9 (26.4%), other side effects 9 (26.4%), cost 1, and other reasons in the remaining 2 patients. Only 17 patients (32%) stated they were doing well on their initial medications; 11 of those (64.7%) were taking hyoscyamine time capsules. Upon subjective failure, 22/36 patients (61.1%) had their medications changed, while 14/36 (38.8%) pursued behavioral therapy without additional medications. Urodynamic studies were done in 12 patients who failed empiric medical treatment (22.6%). Only 32% of elderly women treated medically for UUI were satisfied and continued therapy in this patient population. One-fourth of elderly women failed empiric medical management of UUI due to lack of efficacy, and one-third due to intolerable side effects. In this practice, hyoscyamine was continued more often than any other anticholinergic because of reasonable cost, efficacy, and side effect profile.",2001.0,0,1
82,11126150,Bladder-sphincter biofeedback as treatment of detrusor instability in women who failed to respond to oxybutynin.,A C Wang,"This study was designed to determine the efficacy of bladder-sphincter-biofeedback as a secondary treatment for those women with detrusor instability who failed to respond to oxybutynin chloride. In a prospective non-randomized trial, 31 of 70 women with detrusor instability were assigned to either the study bladder-sphincter-biofeedback training group (n = 16) or to the control pelvic floor exercise group (n = 15) after they had failed to respond to oxybutynin chloride. Thirty (43%) of the 70 women were cured by oxybutynin chloride, and 9 (13%) withdrew due to various side effects. A comparison of cure rates between biofeedback training and pelvic floor exercise groups demonstrated that there were significant differences in objective changes: detrusor pressure (68.75% vs. 0%, p < 0.001), compliance (75.0% vs. 6.67%, p < 0.001), and resting maximal urethral closure pressure (43.75% vs. 6.67%, p < 0.037). Neither the cure rate nor improvement rate of subjective changes (urgency, and frequency and episodes of urge incontinence), significantly differed. Oxybutynin chloride was not well tolerated while bladder-sphincter-biofeedback was well accepted. As a secondary treatment, it appears better than pelvic floor exercise alone and may be the choice of non-surgical treatment in those women who failed to respond to oxybutynin chloride for detrusor instability.",2001.0,0,0
83,11152906,Neonatal outcome of infants born at 23 weeks' gestation.,T F McElrath; J N Robinson; J L Ecker; S A Ringer; E R Norwitz,"To determine the neonatal outcome in accurately dated 23-week deliveries. We reviewed the records of consecutive births between 23 0/7 and 23 6/7 weeks at Brigham & Women's Hospital, Boston, Massachusetts, from January 1995 to December 1999. Women were excluded if they presented for elective termination or had known fetal death or poor dating criteria. Neonatal records were abstracted for mortality and short-term morbidity, including the respiratory distress syndrome (RDS), intraventricular hemorrhage, chronic lung disease, necrotizing enterocolitis, periventricular leukomalacia, and retinopathy of prematurity. Survival was defined as discharge from neonatal intensive care. Thirty-three singleton pregnancies met criteria for inclusion, 11 of whom survived to discharge (survival rate 0.33; 95% CI 0.18, 0.52). More advanced gestational age was associated with increased likelihood of survival: 0 of 12 at 23 0/7 to 23 2/7 weeks, 4 of 10 at 23 3/7 to 23 4/7 weeks, and 7 of 11 at 23 5/7 to 23 6/7 weeks (P =.02). All 11 survivors developed RDS and chronic lung disease. One of 11 survivors had necrotizing enterocolitis, and 2 of 11 had severe retinopathy of prematurity. One survivor had periventricular leukomalacia on head ultrasonography, compared with 7 of the nonsurvivors who had head ultrasonography (P =.03). One survivor developed severe intraventricular hemorrhage (grade 3 or 4) compared with 8 of the 12 at-risk nonsurvivors who had head ultrasonography (P =.01). About one third of infants delivered at 23 weeks' gestation survived to be discharged from neonatal intensive care. More advanced gestational age was associated with increased likelihood of survival. No neonates survived free of substantial morbidity.",2001.0,1,1
84,11164141,Practice patterns in the treatment of female urinary incontinence: a postal and internet survey.,H L Kim; G S Gerber; R V Patel; C M Hollowell; G T Bales,"To survey American urologists to assess practice patterns in treating female incontinence. Advances in the treatment of female incontinence have changed the way urologists practice. Postal and e-mail surveys were sent to 2502 members of the American Urological Association. From the postal group (n = 1000), 419 (42%) responses were obtained; from the e-mail group (n = 1502), 160 (11%) responses were obtained. For types I, II, and III stress urinary incontinence (SUI), 239 (44%) of 546, 388 (68%) of 570, and 512 (94%) of 547 urologists, respectively, recommended a sling procedure. For type I SUI, 75 (53%) of the 143 respondents in practice for less than 10 years recommended a sling procedure. The sling was recommended by 62 (35%) of the 176 respondents in practice for longer than 20 years (P <0.001). Most urologists (75%, 358 of 480) referred patients with significant vaginal prolapse to a gynecologist; however, urologists in full-time academic practice were more likely to offer surgical treatment (56%, 29 of 52). Most urologists recommended medical treatment for urge incontinence (94%, 461 of 491), and the medications most commonly selected were tolterodine (41%, 202 of 491), oxybutynin (26%, 129 of 491), and extended-release oxybutynin (25%, 125 of 491). Overall, a sling procedure was the most commonly recommended surgical procedure for all types of SUI. Most urologists referred patients with significant vaginal prolapse to a gynecologist. For type I SUI, older urologists were more likely than younger urologists to perform needle bladder neck suspension.",2001.0,0,0
85,11165228,Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats.,I Shimizu; K Kawashima; D Ishii; S Oku; H Kohayakawa; M Oka,"In radioligand binding assays, AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl]pyrrolidine fumarate) had high affinity for sigma receptors and moderate affinity for muscarinic receptors. The affinity of AH-9700 for sigma(1) receptors was significantly reduced in the presence of 5'-guanylyl-imidodiphosphate (GppNHp). In isolated bladder strips of rats, AH-9700 inhibited carbachol-induced contractions. In anesthetized rats, i.v. administration of AH-9700 and typical sigma receptor ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), but not oxybutynin, dose-dependently inhibited rhythmic isovolumetric reflex bladder contractions. AH-9700 and oxybutynin suppressed the amplitude of rhythmic bladder contractions. On the other hand, at doses lower than used i.v., the i.c.v. administration of AH-9700 or the sigma receptor ligands inhibited rhythmic bladder contractions without suppressing the amplitude. This inhibitory effect of AH-9700 was markedly reduced by pretreatment with i.c.v. pertussis toxin. These results suggest that AH-9700 exerts a marked anti-micturition reflex effect through central sigma receptors possibly related to pertussis toxin-sensitive Gi/o-proteins and a moderate spasmolytic effect based on its peripheral anti-muscarinic activity.",2002.0,0,0
86,11176403,Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens.,S M Di Stasi; A Giannantoni; G Vespasiani; P Navarra; G Capelli; R Massoud; R L Stephen,"About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond. A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling. There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations. Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.",2001.0,0,0
87,11176516,Use of tolterodine in children with dysfunctional voiding: an initial report.,M Munding; H Wessells; B Thornberry; D Riden,"Tolterodine was recently approved for the treatment of incontinence and overactive bladder in adults, and has fewer side effects than oxybutynin. We evaluated the safety and efficacy of tolterodine in children with dysfunctional voiding. We retrospectively reviewed our experience with 30 pediatric patients treated with tolterodine for a primary diagnosis of dysfunctional voiding. Patients were treated with adult doses of tolterodine and behavioral modifications. Standard definitions determined by the International Children's Continence Society were adapted to designate final treatment outcomes on medication as cured-greater than 90% reduction in wetting episodes, improved-greater than 50% reduction or failed-less than 50% reduction. The children were 4 to 17 years old (mean age 8.7) and were treated with tolterodine for an average of 5.2 months. The final dose was 1 mg. twice daily in 1, 2 mg. twice daily in 27 and 4 mg. twice daily in 2 patients. Wetting episodes were cured in 10 (33%), improved in 12 (40%), and failed to show improvement in 8 (27%) cases. Four patients (13.3%) reported side effects and only 1 discontinued the medication due to diarrhea. There were no reports of hyperpyrexia, flushing or intolerance to sunshine and outdoor temperature. Our results demonstrate that tolterodine at adult doses without titration can be used safely to decrease wetting episodes in children with dysfunctional voiding. Controlled clinical trials should be completed to evaluate further efficacy and safety in children.",2001.0,0,0
88,11207885,Association between oxybutynin and neuropsychiatric adverse effects not confirmed in daily practice.,K L Movig; A C Egberts; A W Lenderink; H G Leufkens,,2001.0,1,1
89,11210400,Lack of effect of food on the pharmacokinetics of an extended-release oxybutynin formulation.,G Sathyan; W Hu; S K Gupta,"The effect of food on the pharmacokinetics of 15 mg oxybutynin XL was evaluated in a single-dose, randomized, crossover, open-label study in healthy volunteers. A validated, stereospecific, high-performance liquid chromatography assay was used to simultaneously determine the plasma concentrations of R- and S-oxybutynin and active metabolite R- and S-desethyloxybutynin. The mean AUC and Cmax values for each of the four analytes in the fed treatment were within +/- 20% of the fasting treatment values. The 90% confidence intervals for the treatment ratios (fed/fasted) for log-transformed Cmax and AUCinf values for the drug isomers and AUCinf values for the metabolite isomers were all within the 80% to 125% range. Only the ranges for the Cmax values for R- and S-desethyloxybutynin were slightly wider but were well within the 70% to 143% criteria recommended for Cmax when comparing effect of food. Lack of effect of food on oxybutynin XL is consistent with the previous observation that the osmotically controlled formulations are nearly insensitive to the gastrointestinal environment, including food. Oxybutynin XL was well tolerated, and the safety results were comparable whether administered alone or with food. In conclusion, oxybutynin XL administration does not require any caution to be exercised regarding food.",2001.0,0,1
90,11248608,Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder.,P Van Kerrebroeck; K Kreder; U Jonas; N Zinner; A Wein; Tolterodine Study Group,"To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder. This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals. Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (P <0.0079) and pad usage (P <0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comparable for the two active groups and the placebo group. No safety concerns were noted. Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation.",2001.0,1,1
91,11269570,Food increases the bioavailability of tolterodine but not effective exposure.,B Olsson; N Brynne; C Johansson; H Arnberg,"The objective of this study was to investigate the influence of food on the pharmacokinetics of tolterodine, its active 5-hydroxymethyl metabolite (5-HM), and exposure to the active moiety (sum of unbound tolterodine + 5-HM) in healthy volunteers. Serum concentrations of tolterodine and 5-HM were measured for up to 12 hours after a single oral dose (2 mg) of tolterodine L-tartrate, administered either on an empty stomach or with a standardized medium-fat breakfast. All 23 subjects completing the study were classified as extensive metabolizers (phenotyped with debrisoquine). Pharmacokinetic data on tolterodine and the active moiety were evaluable for 22 subjects; all completing subjects were evaluable for 5-HM pharmacokinetics. Based on Cmax and AUC(infinity) ratios, relative bioavailability of tolterodine in the presence of food was 1.49 (90% confidence interval [CI], 1.35-1.71) and 1.53 (1.35-1.72), respectively. The pharmacokinetics of 5-HM and the active moiety were unaffected by food, as were the rates of drug absorption and terminal half-lives of tolterodine and 5-HM. Given that bioequivalence was observed for the active moiety underfed and fasting conditions, the authors concluded that coadministration of tolterodine with food is not expected to have any clinically relevant effects.",2001.0,0,1
92,11286323,Food does not influence the pharmacokinetics of a new extended release formulation of tolterodine for once daily treatment of patients with overactive bladder.,B Olsson; J Szamosi,"To determine whether food intake influences the pharmacokinetics of a new, once daily, extended release (ER) capsule formulation of tolterodine in healthy volunteers, and to compare its bioavailability with that of the existing immediate release (IR) tablet. Open, randomised, 3-way crossover trial. 17 healthy volunteers (3 females, 14 males) aged between 19 and 50 years. With the exception of 1 male volunteer, all participants were classified as extensive metabolisers by cytochrome P450 2D6 genotyping. Volunteers received single oral doses of tolterodine L-tartrate ER 8 mg (2 x 4 mg capsules) on an empty stomach or with a standardised high-fat breakfast. Reference therapy comprised tolterodine L-tartrate IR 4 mg (2 x 2 mg tablets), administered in the fasting state. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (sum of unbound tolterodine + 5-HM) were measured for up to 72 hours post-dose. Safety endpoints were also determined. No effect of food on the bioavailability of tolterodine ER capsules was apparent and there was no sign of dose-dumping with meals. The geometric mean fed:fasting ratio of area under the serum concentration-time curve to infinity (AUCinfinity) of the active moiety, for all volunteers combined, was 0.95 (90% confidence interval 0.88 to 1.03). Equivalence with respect to AUCinfinity (dose-corrected) was also found for the ER capsule compared with the IR tablet, although uncorrected maximum serum concentrations were around 50% lower despite the fact that the capsule dose was twice as high. Seven volunteers reported adverse events, predominantly headache. No volunteer reported dry mouth. Overall, there were no safety concerns. The new ER formulation of tolterodine shows no pharmacokinetic interaction with food. On the basis of these results, patients with overactive bladder may, therefore, be advised to take the drug without regard to the timing of meals, maximising convenience during therapy.",2001.0,0,1
93,11294516,Oxybutynin does not affect cyclosporin blood levels.,J E Springate,"Cyclosporin is an important immunosuppressive medication used to prevent organ rejection. Drug interactions that alter its blood levels can cause serious problems with toxicity or transplant rejection. Current evidence indicates that both cyclosporin and oxybutynin, which is used to treat bladder dysfunction, are metabolized by the cytochrome P450 3A enzyme system, raising the possibility of an adverse interaction between these medications. However, a study of two children receiving cyclosporin with and without oxybutynin revealed no significant changes in trough blood cyclosporin concentrations.",2001.0,0,1
94,11298060,The overactive bladder in children: a potential future indication for tolterodine.,K Hjälmås; A L Hellström; K Mogren; G Läckgren; A Stenberg,"To determine the safety, efficacy and pharmacokinetics of tolterodine in children with an overactive bladder. Thirty-three children (20 boys and 13 girls, aged 5-10 years) with an overactive bladder and symptoms of urgency, frequency and/or urge incontinence were enrolled in an open, dose-escalation study. Patients were treated with oral tolterodine 0.5 mg (n = 11), 1 mg (n = 10) or 2 mg (n = 12) twice daily for 14 days. The primary safety endpoint was the change in residual urinary volume, as determined by ultrasonography. In addition, voiding diary variables (frequency and incontinence episodes) and pharmacokinetics were evaluated. Other safety endpoints included laboratory variables, electrocardiogram recordings and reported adverse events. There were no safety concerns in terms of the change in residual urinary volume for any of the three dosage groups; values were comparable with baseline after 2 weeks of treatment for all three dosages. Adverse events were reported by 20 patients (six on 0.5 mg, five on 1 mg, and nine on 2 mg). Most adverse events were not considered to be drug-related; of the 13 possibly related events, 10 occurred in those taking 2 mg. Headache was the most commonly reported adverse event. No serious adverse events were reported and there were no general safety concerns. There was an improvement in voiding diary variables in all treatment groups after 2 weeks of treatment, although the efficacy was greatest in those taking 1 mg and 2 mg. Pharmacokinetic findings were consistent with dose linearity over the range 0.5-2 mg. The results support the use of 1 mg twice daily as the optimal dose of tolterodine for treating children aged 5-10 years with an overactive bladder.",2001.0,0,0
95,11302288,Economics of lower urinary tract symptoms (LUTS) in older people.,U Azam; M Castleden; D Turner,Urinary incontinence is an area of clinical and social importance to older people and providers of care. This article provides an update on the 'symptom' of urinary incontinence and reviews the concept of lower urinary tract symptoms (LUTS). The challenges facing health services researchers working in this field are also discussed in terms of trying to quantify the size and extent of the underlying problem. Economic issues and work undertaken to evaluate the cost of LUTS are appraised and the common nonsurgical treatments for LUTS are described together with associated conditions and their cost implications. The cost to individuals and society of LUTS is generally underestimated and the importance of reducing its severity (if cure is not achievable) makes clinical and economic sense.,2001.0,0,0
96,11322348,,,,,0,0
97,11322350,Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.,R A Appell; P Sand; R Dmochowski; R Anderson; N Zinner; D Lama; M Roach; J Miklos; D Saltzstein; T Boone; D R Staskin; D Albrecht; Overactive Bladder: Judging Effective Control and Treatment Study Group,"To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.",2001.0,1,1
98,11327200,Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine.,B Olsson; J Szamosi,"To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. Nonblind, randomised, 2-way crossover trial. 19 healthy volunteers (7 females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study, all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping. Volunteers received tolterodine ER 4mg once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L-tartrate salt). A washout period of 7 days separated the 2 treatments. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM; poor metabolisers: unbound tolterodine) were measured for up to 48 hours post-dose on day 6 (steady state). Tolerability was also determined. 17 volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study and were evaluable for both treatment periods. The 90% confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours (AUC24) of the active moiety, for all volunteers combined, indicated equivalence for the 2 formulations. Pooled analysis also demonstrated that the peak serum concentration (Cmax) of the active moiety following administration of tolterodine ER was around 75% of that observed for the IR tablet, whereas the trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only) were consistent with sustained drug release over 24 hours. Tolterodine ER was well tolerated. The new once daily ER formulation of tolterodine 4mg shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain the significantly lower rate of dry mouth subsequently observed in patients with overactive bladder.",2001.0,0,1
99,11341475,Tolterodine: a review of its use in the treatment of overactive bladder.,D Clemett; B Jarvis,"Tolterodine is a competitive muscarinic receptor antagonist that shows in vivo selectivity for the bladder over the salivary glands compared with oxybutinin. Results of randomised double-blind placebo-controlled studies indicate that tolterodine 4 mg/day (administered as immediate-release tablets 2mg twice daily or extended-release capsules 4mg daily) is superior to placebo in improving micturition diary variables in patients with overactive bladder. Moreover, tolterodine 2mg twice daily is as effective as oxybutynin 5mg 3 times daily. Maximum treatment effects with both drugs occurred after 5 to 8 weeks of treatment and improvements were maintained during long term treatment for up to 24 months. In a pooled analysis of four 12-week studies, equivalent and significant reductions in micturition frequency (-2.3 and -2.0 vs -1.4, p < 0.001) and the incidence of urge incontinence episodes (-1.6 and -1.8 vs -1.1, p < 0.05) were reported for tolterodine 2mg twice daily and oxybutynin 5mg 3 times daily compared with placebo. Functional bladder capacity was also significantly increased. Improvements in patient perceptions of their urgency symptoms and of problems caused by their bladder condition were significantly greater during treatment with tolterodine than with placebo. Tolterodine was generally well tolerated in clinical trials of up to 24 months' duration. Dry mouth was the most frequent adverse event. The incidence (40 vs 78%, p < 0.001) and intensity of this event was lower with tolterodine 2mg twice daily than oxybutynin 5mg 3 times daily. Additionally, a 23% lower incidence of dry mouth was reported with once daily extended-release tolterodine capsules than with twice daily immediate-release tablets (p < 0.02). The incidence of adverse CNS events with tolterodine was low and similar to that of placebo. Tolterodine was well tolerated in elderly patients and no serious tolerability concerns were identified. Tolterodine is the first antimuscarinic agent to specifically developed for the treatment of overactive bladder. The functional selectivity of tolterodine for the bladder translates into good efficacy and tolerability in patients, including the elderly, with overactive bladder. Tolterodine is as effective as oxybutynin in improving micturition diary variables but is associated with a significantly lower incidence and intensity of dry mouth. This favourable tolerability profile, together with sustained clinical efficacy during long term treatment, places tolterodine as valuable treatment for the symptoms of overactive bladder.",2001.0,0,0
100,11342895,Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial.,J Malone-Lee; B Shaffu; C Anand; C Powell,"We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland. In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments. Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment. Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.",2001.0,1,1
101,11350411,Side-effects of oral or intravesical oxybutynin chloride in children with spina bifida.,P Ferrara; C M D'Aleo; E Tarquini; S Salvatore; E Salvaggio,"To evaluate the incidence of side-effects of oral and intravesical oxybutynin chloride in children with meningomyelocele (MMC) and a neurogenic bladder. The study comprised 225 children with a neurogenic bladder from MMC who were evaluated with urodynamic testing and voiding cysto-urethrography to identify those at high risk of upper tract damage. In all, 101 children (mean age 4.2 years, range 0.25-10) had unco-ordinated detrusor-sphincter function and low compliance; they were treated with either oral or intravesical oxybutynin and clean intermittent catheterization. Of the 101 patients, 67 were treated with oral oxybutynin; in 11 the treatment was discontinued because of the side-effects. The other 34 patients used both clean intermittent catheterization and intravesical oxybutynin. In this group there were side-effects in six patients, including drowsiness, hallucinations and cognitive changes. Oral and intravesical oxybutynin is effective for managing neurogenic bladder dysfunction, but intravesical administration is safer and better tolerated than oral oxybutynin in the treatment of children with MMC. However, adverse effects such as cognitive impairment can also occur in children treated with intravesical oxybutynin and these patients must be closely monitored because these effects may differ from those with oral administration.",2001.0,0,0
102,11357173,A semiparametric deconvolution model to establish in vivo-in vitro correlation applied to OROS oxybutynin.,M Pitsiu; G Sathyan; S Gupta; D Verotta,"In vitro-in vivo correlation (IVIVC) models may be used to predict in vivo drug concentration-time profiles given in vitro release characteristics of a drug. This prediction is accomplished by incorporating in vitro release characteristics as an input function (A(vitro)) to a pharmacokinetics model. This simple approach often results in biased predictions of observed in vivo drug concentrations, and it can result in rejecting IVIVC. To solve this problem we propose a population IVIVC model that incorporates the in vitro information and allows one to quantify possibly changed in vivo release characteristic. The model assumes linear kinetics and describes the in vivo release as a sum of A(vitro) and a nonparametric function (A(d), a spline) representing the difference in release due to in vivo conditions. The function A(vitro) and its variability enter the model as a prior distribution. The function A(d) is estimated together with its intersubject variability. The number of parameters associated with A(d) defines the model: no parameters indicates perfect IVIVC, a large number of parameters indicates poor IVIVC. The number of parameters is determined using statistical model selection criteria. We demonstrate the approach to solve the IVIVC problem of an oral extended release oxybutynin form (OROS), administered in three pharmacokinetic studies. These studies present a particular challenging case; that is, the relative bioavailability for the OROS administration is >100% compared with that of the immediate-release form. The result of our modeling shows that the apparent lack of IVIVC can be overcome: in vivo concentration can be predicted (within or across data sets) based on in vitro release rate together with a simple form of systematic deviation from the in vitro release.",2001.0,0,0
103,11374317,Treatment of overactive bladder: long-term tolerability and efficacy of tolterodine.,R A Appell; P Abrams; H P Drutz; P E Van Kerrebroeck; R Millard; A Wein,"Previously available antimuscarinic therapies for overactive bladder are poorly tolerated due to a high incidence of adverse events, notably dry mouth. Tolterodine is a bladder-selective, antimuscarinic agent for the treatment of frequency, urgency, and urge incontinence that characterize overactive bladder. In a 9-month open-label study, the safety, tolerability, and clinical efficacy of tolterodine 2 mg twice daily was evaluated in 854 patients with overactive bladder symptoms who had completed one of four 12 week randomized, controlled trials of tolterodine. Safety and tolerability were assessed in terms of adverse events and clinical/laboratory variables. Efficacy was assessed using micturition diaries and patient perception of their bladder condition. In all, 70% of patients remained on treatment for 9 months. Dry mouth was the most frequently reported adverse event, occurring in 28% of patients (intensity: 19% mild, 7% moderate, 2% severe). A total of 9% of patients withdrew due to adverse events. Dosage reduction occurred in 13% of patients. Significant improvements (P < 0.0001) in micturitions per 24 h (-22%), urge incontinence episodes per 24 h (-76%) and volume voided per micturition (+22%) were observed after 9 months of treatment, with 65% of patients reporting an improvement in perception of their bladder problems. The incidence of adverse events and improvements in micturition diary variables during open-label treatment were comparable with those observed during a 12 week randomized treatment. It was concluded that tolterodine is well tolerated and maintains its clinical efficacy during 9 months of treatment. The high proportion of patients remaining on treatment indicates that tolterodine is an effective long-term treatment for overactive bladder.",2001.0,1,1
104,11392625,Clinical experiences with tolterodine.,L Nilvebrant,"Tolterodine is the first muscarinic receptor antagonist that has been specifically developed for the treatment of overactive bladder. The objectives in the discovery program were to design a potent muscarinic receptor antagonist that is equipotent to oxybutynin in the bladder, but less potent in salivary glands, with the aim of improving tolerability (less dry mouth) in patients with overactive bladder. Tolterodine is non-selective with respect to the muscarinic M1-M5 receptor subtypes, but has a greater effect on the bladder than on salivary glands in vivo, in both animals and humans. Clinical results show that the efficacy and safety of tolterodine in overactive bladder is equal to that of oxybutynin, but that tolterodine is significantly better tolerated by the patients.",2001.0,0,0
105,11394733,A comparison of the effects on saliva output of oxybutynin chloride and tolterodine tartrate.,M B Chancellor; R A Appell; G Sathyan; S K Gupta,"Oxybutynin chloride and tolterodine tartrate are anticholinergic agents used to suppress involuntary bladder contractions in urinary incontinence. They act by inhibiting binding of acetylcholine to the muscarinic receptors in the detrusor muscle of the bladder. The same types of muscarinic receptors are found in the salivary glands; thus anticholinergic agents may decrease saliva production and cause dry mouth, a commonly cited reason for discontinuation of therapy. The primary objective of this study was to compare saliva output, which is an objective measure of dry mouth, in subjects taking immediate- or extended-release oxybutynin, tolterodine, or placebo. This was a single-site, single-dose, randomized, double-blind, 4-treatment, 4-period crossover study. Subjects were randomly assigned to 1 of 4 treatment sequences that included extended-release oxybutynin 10 mg, tolterodine 2 mg, immediate-release oxybutynin 5 mg, and placebo. Saliva output was measured objectively before dosing with each treatment and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Thirty-six healthy adult volunteers (22 women and 14 men) participated in the study. They ranged in age from 19 to 42 years (mean, 27 years). Thirty-one were white, 3 Asian, and 2 black. There were no significant differences in predose saliva output between the 4 study groups. With placebo, saliva output increased throughout the day. Saliva output was maintained at predose levels throughout the day with extended-release oxybutynin. Two hours after dosing with tolterodine and immediate-release oxybutynin, saliva output decreased nearly 0.5 g in specimens collected over 2 minutes. All 3 active treatments were associated with lower saliva output compared with placebo. Extended-release oxybutynin and tolterodine were similar with respect to area under the saliva concentration-time curve but were associated with significantly greater saliva output than was immediate-release oxybutynin (P < 0.01). There were no serious adverse events (AEs) in this study. AEs were similar between treatments, although the incidence of headache was higher in the active-treatment groups than with placebo. Objective assessment of saliva output in healthy adult volunteers indicated that extended-release oxybutynin and tolterodine had less impact on saliva output than did conventional immediate-release oxybutynin, suggesting that they may yield lower levels of dry mouth.",2001.0,0,1
106,11402632,"Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system.",A Todorova; B Vonderheid-Guth; W Dimpfel,"Antimuscarinic compounds are increasingly used to treat the symptoms of overactive bladder; however, their use is often restricted by peripheral adverse effects (AEs). On the other hand, data regarding their influence on the central nervous system (CNS) are limited. This randomized, single-blind, parallel-group quantitative-topographical EEG (qEEG) study of clinical phase I investigates the potential CNS adverse effects of the three antimuscarinic drugs--tolterodine, oxybutynin, and trospium chloride--in comparison to placebo. Overall, 4 x 16 (total 64) young, healthy male volunteers were included in the study. The subjects were given either placebo or the clinically recommended daily doses of the drugs dispensed in three doses on a single day (tolterodine 2 mg bid and once placebo, total 4 mg/d; oxybutynin 5 mg tid, total 15 mg/d; and trospium chloride 15 mg tid, total 45 mg/d). The qEEG was recorded prior to and up to 4 hours after each intake of the trial medication (a total of 10 qEEG sessions) under three different conditions: at rest with eyes open, eyes closed, and under mental demand. The drug tolerability was subjectively evaluated by the volunteer and the investigator. In comparison to placebo (10% confidence interval), tolterodine and trospium chloride did not induce changes of the qEEG power in five of the six frequency bands (i.e., delta, alpha 1, alpha 2, beta 1, and beta 2). Isolated power decreases were only observed in the theta frequency band. In contrast, oxybutynin caused significant power reductions in four frequency bands (theta, alpha 1, alpha 2, and beta 1; p < 0.01). The subjectively evaluated drug tolerability was comparable between all treatment groups, although differences in the AE occurrence existed, with the AE frequency being higher in the oxybutynin group. The results of this study support the findings that oxybutynin as a tertiary amine crosses the blood-brain barrier, causing significant qEEG activity changes and more pronounced central adverse effects. Although tolterodine is also a tertiary amine, it shows limited effects on qEEG activity (i.e., slight theta power reductions), comparable to the effects of trospium chloride, a quarternary amine, which barely crosses the blood-brain barrier. The minimal qEEG changes observed with tolterodine and trospium chloride reflect most probably a rebound message from the peripheral target organs. Prescription of oxybutynin thus implicates a higher risk of CNS side effects.",2002.0,0,0
107,11435842,"A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence.",G W Davila; C A Daugherty; S W Sanders; Transdermal Oxybutynin Study Group,"We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence. Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system. A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema. Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.",2001.0,0,1
108,11435843,A crossover randomized trial of transcutaneous electrical nerve stimulation and oxybutynin in patients with detrusor instability.,N A Soomro; M H Khadra; W Robson; D E Neal,"Management of idiopathic detrusor instability is difficult in most patients mainly due to the lack of a complete understanding of the pathophysiology. Oxybutynin and transcutaneous electrical nerve stimulation have been used but to our knowledge no direct comparisons have been made. Patients with frequency, urgency, urge incontinence and proved detrusor instability were studied with urodynamics, quality of life instruments, and frequency and volume charts. Patients were randomized to transcutaneous electrical nerve stimulation or oxybutynin. After 6 weeks of treatment, they were reassessed and after a washout of 2 weeks, they were started on the second arm of treatment and reassessed 6 weeks later. A total of 13 male and 30 female patients were studied. Functional capacity had increased and number of voids daily had decreased significantly compared with before treatment in both arms (p <0.005). There were significant improvements in symptom specific quality of life measures but no changes were found on the global Short Form 36 (SF-36) quality of life questionnaire. The volume to first desire to void and first unstable contraction had increased significantly with oxybutynin but not with transcutaneous electrical nerve stimulation. Of 23 patients 7 were stabilized with treatment, including 2 with oxybutynin only, 2 with either nerve stimulation or oxybutynin and the remaining 3 with only nerve stimulation. Total bladder capacity did not change significantly with either treatment but patients noticed side effects more commonly with oxybutynin. Both treatments clearly improved subjective parameters. However, only oxybutynin showed significant improvements in objective urodynamic parameters. Transcutaneous electrical nerve stimulation can be used in patients who cannot take oxybutynin. Further studies are needed to show the long-term efficacy and cost analyses of nerve stimulation.",2001.0,1,1
109,11454106,Tolterodine: a safe and effective treatment for older patients with overactive bladder.,J G Malone-Lee; J B Walsh; M F Maugourd,"To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder. Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study. Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland. One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours). Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks. Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours. The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo. Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder.",2001.0,1,1
110,11454125,Urinary incontinence management: new questions from old assumptions.,C E DuBeau,,2001.0,0,0
111,11479003,Therapeutic opportunities from muscarinic receptor research.,R M Eglen; A Choppin; N Watson,"Muscarinic acetylcholine receptor subtypes have been the subjects of research for at least a quarter of a century. Nonetheless, there are few selective muscarinic receptor ligands presently used as therapeutics. The extensive development of muscarinic M(1) receptor agonists for the treatment of cognitive dysfunction has culminated in a series of unsuccessful drug candidates, which reflects a lack of understanding of the disease and the role played by muscarinic cholinergic transmission. Paradoxically, the most successful antagonist approved for use in urinary incontinence is the nonselective muscarinic receptor antagonist tolterodine. This deficit in subtype-selective ligands could be circumvented by the development of transgenic mice, each lacking functional M(1), M(2), M(3), M(4) or M(5) receptors. In this article, the current status of muscarinic receptor research is critically assessed.",2001.0,0,0
112,11482747,Twelve-month treatment of overactive bladder: efficacy and tolerability of tolterodine.,P Abrams; J Malone-Lee; B Jacquetin; J J Wyndaele; T Tammela; U Jonas; A Wein,"Tolterodine is a bladder-selective antimuscarinic agent designed for the treatment of overactive bladder. Traditional antimuscarinic therapies are poorly tolerated due to a high incidence of anticholinergic adverse events and consequently few patients remain on long term therapy. To evaluate the long term efficacy and tolerability of tolterodine in patients with symptoms of overactive bladder. Twelve-month open-label extension of 4 randomised, placebo-controlled, double-blind, multinational, multicentre trials of 4 weeks' duration. 714 patients (aged 18 to 92 years) with symptoms of overactive bladder who completed the double-blind portion of the studies. Tolterodine 2 mg twice daily for up to 12 months. Micturition diary variables: number of micturitions per 24 hours, number of urge incontinence episodes per 24 hours, mean urine volume voided per micturition. Safety variables: adverse events, study discontinuation rate. A total of 441 patients (62%) completed 12 months' open-label treatment with tolterodine, which significantly reduced the number of micturitions per 24 hours [mean change -2.4, 95% confidence interval (CI) -2.7 to -2.2, median change -20%, p < 0.0001] and number of urge incontinence episodes per 24 hours (mean change -1.3, 95% CI -1.6 to -1.0, median change -74%, p < 0.0001), while the mean volume voided per micturition was significantly increased (+33 ml, 95% CI +28 to +38, median change +18%; p < 0.0001). 41% of patients reported dry mouth (27% mild, 10% moderate, 3% severe). Dosage reduction to 1 mg twice daily was required in 23% of patients. 15% of patients withdrew from the study due to adverse events, with 5% having associated dry mouth. The high percentage of patients completing 12 months' treatment indicates that tolterodine is an effective and well tolerated agent for long term treatment of overactive bladder.",2002.0,0,0
113,11485135,Failure of tolterodine to treat clozapine-induced nocturnal enuresis.,B A English; D J Still; J Harper; S R Saklad,"To report the use and subsequent failure of the bladder-selective agent tolterodine, to treat clozapine-induced nocturnal enuresis in an adolescent patient with psychotic illness. A 16-year-old Hispanic girl was admitted to the state psychiatric hospital with a diagnosis of bipolar disorder with psychotic features. Clozapine therapy was initiated, and after three months of treatment the patient began experiencing episodes of nocturnal enuresis. The bladder-selective agent tolterodine was tried and subsequently failed to resolve the enuresis episodes. Desmopressin was initiated, which resulted in amelioration of symptoms. This is the first published report of using tolterodine to treat clozapine-induced nocturnal enuresis. Several methods to decrease clozapine-induced urinary incontinence have been used and typically include the addition of agents with high anticholinergic properties. Tolterodine is a bladder-selective anticholinergic agent indicated for the treatment of urinary urge incontinence and may be employed as a treatment for antipsychotic-induced incontinence. Nocturnal enuresis is an adverse effect that infrequently occurs with use of clozapine therapy. Although tolterodine was ineffective in our patient to treat clozapine-induced nocturnal enuresis, further trials are required to appropriately evaluate the effectiveness of tolterodine to treat this adverse drug reaction.",2002.0,0,0
114,11485700,Is extended-release oxybutynin (Ditropan XL) or tolterodine (Detrol) more effective in the treatment of an overactive bladder?,N M Hartnett; B G Saver,,2001.0,0,1
115,11496941,Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers.,R H Zobrist; B Schmid; A Feick; D Quan; S W Sanders,"To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration. OXY was administered either as a single transdermal system over a 96 h wear period or as a single 5 mg immediate-release tablet to 18 healthy male and female subjects in a randomized, open-label, two-way crossover design. Blood samples were collected for 108 h after application of the transdermal system and for 6 h after oral administration. Plasma concentrations of the R- and S-enantiomers of OXY and DEO were assayed by LC-MS/MS. Enantiomer in vitro skin flux was evaluated using human cadaver skin. In vitro skin flux studies demonstrated equal absorption of R and S- OXY. Plasma concentrations and pharmacokinetic parameters of the R-enantiomers of OXY and DEO were slightly lower than the S-enantiomers following transdermal OXY. The relative AUC values were S-OXY>S-DEO>R-OXY>R-DEO. The AUC ratios of DEO/ OXY were less than 1 for both the R- and S- enantiomers. Following oral dosing, plasma DEO concentrations greatly exceeded OXY resulting in relative AUC values of R-DEO>S-DEO>S-OXY>R-OXY. The mean AUC ratios of S- and R-DEO/OXY were 3.25 and 8.93, respectively. Stereoselective metabolism of OXY was evident following both transdermal and oral administration of OXY. The reduced pre-systemic metabolism of transdermally administered OXY compared to oral administration resulted in not only significantly lower DEO plasma concentrations, but also a different metabolite pattern. The differences between R-OXY and R-DEO following the two routes of administration support the potential for comparable clinical efficacy and reduced anticholinergic side-effects with transdermal treatment.",2002.0,0,0
116,11501617,Modern pharmacotherapy of urge urinary incontinence in the USA: tolterodine and oxybutynin.,E S Rovner; A J Wein,,2001.0,0,0
117,11504608,,,,,0,0
118,11519898,Combined pharmacotherapy for nocturnal enuresis.,K Kaneko; S Fujinaga; Y Ohtomo; T Shimizu; Y Yamashiro,"Nocturnal enuresis is a common childhood disorder. Tricyclic antidepressants and anticholinergic agents have been the well accepted pharmacological treatment for this disorder and are efficacious in 40-70% and 10-50% of cases, respectively. The present study was performed to evaluate the effect of a combined treatment of tricyclic antidepressant and an anticholinergic agent. Twenty-two children aged 6-12 years with primary monosymptomatic nocturnal enuresis who did not prefer to use a conditioning alarm were given a combined treatment of these drugs. After a control period of 1 month, each patient was treated for 6 months and then observed for 3 months. A 30-mg dose of amitriptyline or imipramine was given with either 2-4 mg oxybutinin or 10-20 mg propiverine. Efficacy was determined relative to the number of wet nights per week compared with the control period, with more than a 50% decrease in wet nights per week taken to indicate efficacy. The mean wet nights per week decreased from 6.1 to 1.7 (P<0.01), and efficacy was established in 20 patients (90.9%). Relapses occurred in 60.0% of patients during the follow-up period. No significant side effects were observed. The efficacy of the combined therapy in monosymptomatic nocturnal enuresis appears to be greater than that reported for either drug alone, and therefore can be a choice of treatment in order to motivate children with nocturnal enuresis.",2002.0,0,0
119,11522122,Safety profile of tolterodine as used in general practice in England: results of prescription-event monitoring.,D Layton; G L Pearce; S A Shakir,"Unstable bladder symptoms are a common problem in general practice. Drug therapy with anticholinergic drugs is frequently used in the management of this condition. However such drugs are associated with a high incidence of anticholinergic adverse effects. Tolterodine is a competitive anticholinergic agent, selective for the bladder as opposed to the salivary glands. To monitor the safety of tolterodine as used in general practice patients in England for the treatment of urinary frequency, urgency and incontinence. Prospective observational cohort study. 14,526 patients [mean age 62.7 (SD 16.4) years; 68.6% female]. Patients prescribed tolterodine in general practice, soon after the release of the drug in the UK, were followed up for a minimum of 6 months using the technique of prescription-event monitoring (PEM). The most common adverse events reported were dry mouth, headache, malaise, constipation, dyspepsia, nausea and vomiting and pain in abdomen. We identified some uncommon events as possible adverse drug reactions--notably hallucinations, tachycardia and palpitations. The prevalence of these events was compared with that in patient cohorts for other drugs on the PEM database. The age- and sex-adjusted relative risk of hallucinations on tolterodine compared with 10 drugs of other therapeutic classes, and with terodiline, another drug indicated for bladder instability, was 4.85 [95% confidence interval (CI) 2.72 to 8.66] and 1.25 (95% CI 0.62 to 2.53), respectively. There was no significant difference for tachycardia/palpitation in this comparison. Tolterodine is well tolerated in general practice at the recommended daily dose. Hallucinations, tachycardia and palpitations are infrequently associated with the drug.",2002.0,1,1
120,11526802,Managing incontinence due to detrusor instability.,,"Urinary incontinence affects around 3.5 million people of all ages in the UK. For many, incontinence severely restricts their routine activities and damages their quality of life and self-esteem. In about one-third of women sufferers, and around a half of all men with incontinence, the cause is detrusor instability. This condition is characterised by involuntary bladder contractions or pressure rises during bladder filling, which result in a strong or uncontrollable urge to pass urine and, often, incontinence. Here, we consider a primary care-based approach to managing urinary incontinence in adults, concentrating on the medical management of detrusor instability.",2001.0,0,0
121,11527561,Automatic orienting of visuospatial attention in Parkinson's disease.,K A Briand; W Hening; H Poizner; A B Sereno,"The basal ganglia are involved in not only motor behavior, but also other more cognitive processes, such as attention. We tested Parkinson's disease (PD) patients in a task that measures reflexive orienting of spatial attention. Seven patients with idiopathic PD and eight control subjects performed a covert orienting task where spatial attention was directed by means of exogenous cues (luminance increments) with no predictive validity for target position. The subjects' task was to make a speeded saccade to a visual target, which appeared a variable time after onset of the cue either in the cued or an uncued spatial position. There was no overall difference between PD patients and control subjects in terms of the initial facilitation following reflexive cues, and later inhibition of return (IOR). However, PD patients differed from control subjects in two important respects. First, they were significantly faster than were control subjects on this reflexive visual-orienting task. Second, disease severity correlated with attentional performance; more advanced patients showed less initial facilitation but greater IOR. Thus PD patients show better performance on a reflexive saccade task and, for more advanced patients, greater IOR than control subjects. These findings are consistent with the possibility that reflexive attentional processes in PD patients may be more active.",2001.0,0,0
122,11547107,Changing concepts concerning the management of vesicoureteral reflux.,C D Herndon; M DeCambre; P H McKenna,"Conservative estimates indicate that up to 54% of patients who present with vesicoureteral reflux have dysfunction voiding. Children with voiding dysfunction and vesicoureteral reflux historically have a high breakthrough infection rate of 34% to 43%. Breakthrough infection represents significant morbidity and it is the most common indication for surgical intervention for vesicoureteral reflux. Voiding dysfunction is present in 79% of patients who proceed to reflux surgery. We evaluated the impact of pelvic floor muscle retraining combined with a medical program in patients with voiding dysfunction and vesicoureteral reflux. Children with a history consistent with voiding dysfunction and vesicoureteral reflux were screened by uroflowmetry/electromyography, bladder scan for post-void residual urine, renal ultrasound and voiding cystourethrography. Confirmed cases of voiding dysfunction and vesicoureteral reflux were prospectively enrolled in this study. Children participated in an interactive, computer assisted, pelvic floor muscle retraining program that involved a conservative medical regimen and pelvic floor muscle retraining. All patients received prophylactic antibiotics. We evaluated the rate of breakthrough urinary tract infection, reflux outcome and surgical intervention. A literature review with the key words vesicoureteral reflux, voiding dysfunction and urinary tract infection was performed to identify historical control cases for comparison. Study enrollment criteria were fulfilled by 49 girls and 4 boys 4 to 13 years old (average age 8.8), representing 72 units with low grades I to II (48) and high grades III to V (24) reflux. Mean followup was 24 months. Initial uroflowmetry/electromyography and bladder scan revealed a staccato flow pattern and normal post-void residual urine in 11% of cases, staccato flow pattern and elevated post-void residual urine in 10%, flattened flow pattern and normal post-void residual urine in 28%, and flattened flow pattern and elevated post-void residual urine in 51%. Breakthrough infection developed in 5 patients (10%), including 1 in whom reflux had resolved and 1 with grade I reflux who underwent observation. The parents of 2 patients elected to complete biofeedback without surgical intervention and these patients did not have a repeat infection. Reimplantation was performed in 1 case (2%). There was resolution in 18 low and 7 high grade refluxing units, including 2 older patients with a long history of high grade bilateral disease. Average time to resolution was 7.8 months. We noted elevated post-void residual urine in 88% of the patients with high grade reflux. Average age at resolution was 9.2 years. During a 24-month period one of us (P. H. M.) noted a greater than 90% decrease in surgical intervention. A combined conservative medical and computer game assisted pelvic floor muscle retraining program appears to have decreased the incidence of breakthrough urinary tract infections and facilitated reflux resolution in children with voiding dysfunction and vesicoureteral reflux. Patients with high grade reflux and voiding dysfunction commonly present with elevated post-void residual urine, contraindicating the indiscriminate administration of anticholinergics. Decreasing the rate of urinary tract infections may have a dramatic impact on the need for surgical intervention and enable the reflux resolution rate to approximate that in patients without voiding dysfunction. Prospective controlled trials are needed to determine whether pelvic floor muscle retraining combined with a conservative medical regimen alters the natural history of vesicoureteral reflux in patients with voiding dysfunction.",2002.0,0,0
123,11548979,Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS.,M Chen; B Gran; K Costello; K Johnson; R Martin; S Dhib-Jalbut,"Glatiromer acetate (GA) is an approved treatment for multiple sclerosis (MS). The proposed mechanism of action is the induction of GA-specific T cells characterized by protective anti-inflammatory Th2 response. We tested this hypothesis in 11 MS patients treated with GA from 1-19 months. Interferon-gamma and IL-5 (markers of Th1 and Th2 responses respectively) were assayed by ELISA in GA-specific T-cell lines (TCL) supernatants. Th1/Th2 bias was defined based on the ratio of IFN-gamma/IL-5 secretion. Fifty-eight pre-treatment and 75 on-treatment GA-specific TCL were generated. On-treatment mean IL-5 levels in GA-TCL increased significantly, whereas those for IFN-gamma were markedly reduced. Consequently, the ratio of IFN-gamma IL-5 also shifted in favor of a Th2 response. The percentage of GA-TCL classified as Th1 was decreased, whereas those classified as Th2 increased on-treatment as compared to pre-treatment. Some GA-specific TCL, (approximately 25%) generated during treatment secreted predominantly IL-5 in response to MBP and the immunodominant MBP peptide 83-99, indicating that these crossreactive antigens can act as partial agonists for GA-reactive TCL. These results strongly suggest that the mechanism of action of GA in MS involves the induction of crossreactive GA-specific T cells with a predominant Th2 cytokine profile.",2002.0,0,0
124,11597535,Role of urethrocystoscopy in the evaluation of refractory idiopathic detrusor instability.,A Groutz; A Samandarov; R Gold; D Pauzner; J B Lessing; D Gordon,"To assess the role of diagnostic urethrocystoscopy in the evaluation of women with idiopathic detrusor instability (DI) refractory to conventional pharmacologic management. One hundred consecutive women (mean age 62.1 +/- 15.1 years) with idiopathic DI refractory to conventional pharmacologic management were prospectively enrolled. All patients underwent a meticulous evaluation, including a detailed history, urogynecologic questionnaire, micturition diary and pad test, urinalysis and culture, physical examination, and urodynamic studies. Refractory DI was defined as the lack of clinical improvement after at least 6 months of conventional drug therapy. These patients underwent additional evaluation with diagnostic urethrocystoscopy. All patients had a normal urinalysis and negative cytologic findings. Diagnostic urethrocystoscopy revealed isolated bladder tuberculosis in one and transitional cell carcinoma in another. Seven other patients had bladder diverticula (only one of which was also diagnosed by sonographic examination) and 22 had mild-to-moderate bladder trabeculations. The absence of other alarming signs (ie, recurrent urinary tract infection, hematuria, significant residual urinary volume, positive cytologic findings, or suspicious sonographic findings) cannot confirm the lack of significant lower urinary tract abnormalities among patients with refractory DI. Diagnostic urethrocystoscopy, a simple and safe office procedure, facilitates timely diagnosis and appropriate treatment for these patients.",2002.0,0,0
125,11674898,POEMS (patient-oriented evidence that matters) spark discussion.,B D Weiss,,2002.0,0,1
126,11678784,Effect of OROS controlled-release delivery on the pharmacokinetics and pharmacodynamics of oxybutynin chloride.,G Sathyan; M B Chancellor; S K Gupta,"Aims : Dry mouth is a common side-effect seen with immediate-release oxybutynin (IR-Oxy). Ditropan XL [(Oxy-XL), a controlled-release formulation of oxybutynin chloride, is a once-daily oral dosage form that incorporates the OROS technology. Dry mouth as the pharmacodynamic measure was compared between Oxy-XL and IR-Oxy administration. The steady state stereospecific pharmacokinetics were also established for the two formulations and the kinetic-dynamic relationship of oxybutynin was examined. This was a randomized, repeated-dose, double-blind, two-treatment, two-period, crossover study. After a baseline assessment day, volunteers were randomly assigned to one of two treatment sequences and received 4 days of each treatment with a washout period of 7 days between treatments. The treatments were: 1) Oxy-XL 10 mg in the morning and placebo 8 h later, and 2) IR-Oxy 5 mg in the morning and again 8 h later. Volunteers assessed dry mouth severity subjectively using a 100 mm visual analogue scale, VAS (Baseline, treatment days 1 and 4) and objectively by collecting saliva (Baseline and treatment day 4) before dosing and every hour after the morning dose for approximately 16 h. Several blood samples were collected during each treatment, with frequent sampling on day 4 to analyse for plasma R- and S-oxybutynin and R- and S-desethyloxybutynin concentrations. Relatively constant plasma concentrations of oxybutynin and its metabolite were seen over 24 h following Oxy-XL administration with the degree of fluctuation being much lower (P = 0.001; 66% to 81% reduction for the various analytes) than IR-Oxy. Compared with IR-Oxy, Oxy-XL yielded higher (131% and 158% for the R- and S-isomer, respectively) oxybutynin and lower (62% and 78% for the R- and S-isomer, respectively) desethyloxybutynin bioavailability, suggesting reduced first-pass metabolism. Saliva output (area under the effect curve) was significantly higher [P = 0.001; 37% (95% confidence interval: 24, 51%)] with Oxy-XL than with IR-Oxy and, accordingly, dry mouth severity (VAS) integrated over the day was significantly lower with Oxy-XL. The decrease in saliva output and the consequent increase in dry mouth severity correlated with the metabolite R-desethyloxybutynin concentration, and no apparent relationship was observed with the R-oxybutynin concentration. This suggests that the metabolite may contribute to the dry mouth. Therefore, the reduction in metabolite exposure with Oxy-XL may be a possible explanation for the observed decrease in dry mouth severity with OXY-XL compared with IR-Oxy. Oxy-XL maintains relatively constant plasma drug and metabolite concentrations and minimizes first-pass metabolism of oxybutynin. The metabolite appears to contribute to dry mouth associated with oxybutynin, and following Oxy-XL metabolite exposure is reduced compared with IR-Oxy. Consequently less dry mouth was observed with Oxy-XL as compared with IR-Oxy.",2002.0,0,1
127,11702910,Medical treatment of overactive bladder.,R Rackley; A Wein; D Nelson,,2002.0,0,0
128,11711378,Tolterodine once-daily in treatment of the overactive bladder.,K M Peters; R R Huang,,2002.0,0,0
129,11733916,Urethral catheterization in hypospadias surgery: Should the device enter the bladder or be made a urethral stent?,I S Arda; M Mahmutoğlu,"Although bladder catheterization causes contractions, accidental removal and urinary retention are risks of stents in hypospadias repair. An 8F feeding tube was used as a stent in 22 patients (group I). In the other 22 patients (group II), the same size catheter was passed into the bladder, and oxybutynin chloride was administered. The elapsed time to first voiding, pain, and straining was observed in group I and the groups were compared regarding time of catheter removal, accidental removal of catheter/stent, hospital stay, and complications. All stented patients strained at first voiding. Nineteen showed pain, and only 5 voided in the first 8 hours. The catheterized group had no such problems. Time of catheter/stent removal and hospital stay were similar. Three stents were dislodged in patients with significant straining. Meatal stricture was noticed in 5 and 3 patients and fistula in 5 and 2 patients of group I and II, respectively. Complications were significant in patients whose stents were removed accidentally. Stenting led to significant patient irritability with voiding problems. The authors believe that this caused displacement and accidental removal of the stent and eventually resulted in meatal stenosis and fistula. The findings show that bladder catheterization prevents these complications. J Pediatr Surg 36:1829-1831.",2002.0,0,0
130,11735757,Potentially inappropriate medication use in the community-dwelling elderly: findings from the 1996 Medical Expenditure Panel Survey.,C Zhan; J Sangl; A S Bierman; M R Miller; B Friedman; S W Wickizer; G S Meyer,"Inappropriate medication use is a major patient safety concern, especially for the elderly population. Using explicit criteria, prior studies have found that 23.5% and 17.5% of the US community-dwelling elderly population used at least 1 of 20 potentially inappropriate medications in 1987 and 1992, respectively. To determine the prevalence of potentially inappropriate medication use in community-dwelling elderly persons in 1996, to assess trends over 10 years, categorize inappropriate medication use according to explicit criteria, and to examine risk factors for inappropriate medication use. Respondents aged 65 years or older (n = 2455) to the 1996 Medical Expenditure Panel Survey, a nationally representative survey of the US noninstitutionalized population were included. A 7-member expert panel was convened to categorize inappropriate medications. Prevalence of use of 33 potentially inappropriate medications. In 1996, 21.3% (95% confidence interval [CI], 19.5%-23.1%) of community-dwelling elderly patients in the United States received at least 1 of 33 potentially inappropriate medications. Using the expert panel's classifications, about 2.6% of elderly patients (95% CI, 2.0%-3.2%) used at least 1 of the 11 medications that should always be avoided by elderly patients; 9.1% (95% CI, 7.9%-10.3%) used at least 1 of the 8 that would rarely be appropriate; and 13.3% (95% CI, 11.7%-14.9%) used at least 1 of the 14 medications that have some indications but are often misused. Use of some inappropriate medications declined between 1987 and 1996. Persons with poor health and more prescriptions had a significantly higher risk of inappropriate medication use. Overall inappropriate medication use in elderly patients remains a serious problem. Despite challenges in using explicit criteria for assessing inappropriate medications for elderly patients, such criteria can be applied to population-based surveys to identify opportunities to improve quality of care and patient safety. Enhancements of existing data sources to include dosage, duration, and indication may augment national improvement and monitoring efforts.",2002.0,0,0
131,11737484,Identification of muscarinic receptor subtypes of cultured smooth muscle cells and tissue of human bladder body.,H Kiwamoto; F H Ma; H Higashira; Y C Park; T Kurita,"Muscarinic receptor subtypes of cultured smooth muscle cells from the human bladder body were investigated by the receptor binding assay method. The result was compared with that obtained from the human bladder body tissue to confirm whether the receptor subtypes of the cells are not changed after several passages of cell culture. Inhibitory effects of various muscarinic antagonists on the binding of [3H]-N-methylscopolamine ([3H]-NMS) to membrane preparations obtained from cultured smooth muscle cells from the fourth subculture of the human bladder body were compared with those prepared from the human bladder body tissue and cells expressing human muscarinic receptor subtypes. Binding-inhibition constants (pKi) for atropine, pirenzepine, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), oxybutynin and propiverine obtained from membrane preparations of cultured smooth muscle cells were 8.91, 6.35, 8.24, 8.53, 7.29 and 5.61, respectively. pKi values of these muscarinic receptor antagonists against the membrane preparation of human bladder body tissue were 9.08, 6.66, 8.05, 8.79, 7.53 and 6.04, respectively. pKi values of cultured smooth muscle cells and tissue from human bladder body were correlated closely with those of insect cells expressing the cloned human M2 receptor subtype. The binding affinities for various muscarinic receptor antagonists of cultured human smooth muscle cells were maintained through the fourth subculture and it was suggested that the M2 receptor subtype is predominantly expressed in cultured smooth muscle cells of human bladder body as well as in tissue of the human bladder body.",2002.0,0,0
132,11741629,Prescription-event monitoring and reporting of adverse drug reactions.,E Heeley; J Riley; D Layton; L V Wilton; S A Shakir,"Newly marketed drugs in the UK are marked with a black triangle, indicating that doctors should report all adverse drug reactions associated with them to the Committee on Safety of Medicines (CSM). However, under-reporting of adverse reactions is frequent. Our aim was to establish what types of adverse reactions are under-reported to the CSM by family doctors who work in England. We used prescription-event monitoring data obtained for 15 newly marketed drugs. Only 9% (376) of 4211 events found on prescription-event monitoring were reported to the CSM. However, 53% (27) of 51 events classified as serious adverse drug reactions were reported. Overall, serious events were five times more likely to be reported to the CSM than non-serious events. Our results should not be extrapolated to calculate incidence rates of adverse drug reactions in the community from spontaneous reports.",2002.0,0,0
133,11742595,Is tolterodine (Detrol) or oxybutynin (Ditropan) the best for treatment of urge urinary incontinence?,J Blonski,,2002.0,0,0
134,11746614,Motor imagery in Parkinson's disease: a PET study.,R Cunnington; G F Egan; J D O'Sullivan; A J Hughes; J L Bradshaw; J G Colebatch,"We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically ""off"" and after turning ""on"" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both ""off"" and ""on."" Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both ""off"" and when ""on"") and ipsilateral premotor cortex (when ""off"" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task ""on"" compared with their performance when ""off."" PD patients when imagining movement and ""off"" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when ""on."" Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.",2002.0,0,0
135,11747044,The impact of non-compliance on the cost-effectiveness of pharmaceuticals: a review of the literature.,D A Hughes; A Bagust; A Haycox; T Walley,"Non-compliance with drug therapies not only limits their effectiveness, but in some instances, is associated with grave clinical sequelae and substantial economic burden. It is important, therefore, to consider non-compliance in economic evaluations. A review of pharmacoeconomic evaluations, which have applied sensitivity analysis to non-compliance rates, was undertaken to evaluate the impact of non-compliance on the cost-effectiveness of different drug therapies. Although 22 evaluations satisfied the inclusion criteria, additional information was obtained from the authors of most studies, as the published details were inadequate. The majority of evaluations assumed altered effectiveness owing to reduced compliance in the absence of supportive clinical evidence. Because of the disparity in the nature of the outcomes, the measures of non-compliance and the time horizon of the studies evaluated, it was not possible to compare the magnitude of the impact of non-compliance among different drug-disease combinations. However, it was evident that non-compliance always results in a reduction in efficacy, but its impact on costs varied substantially. The importance of incorporating measures of compliance is highlighted, as failing to account for 'real world' compliance rates in pharmacoeconomic evaluations may lead to selection of sub-optimal treatment strategies.",2002.0,0,0
136,11760777,Which muscarinic receptor is important in the bladder?,T Yamanishi; C R Chapple; R Chess-Williams,"Antimuscarinic agents are the most widely used therapy for urge incontinence, but have side effects such as constipation, tachycardia and dry mouth, resulting from a lack of selectivity for the bladder. M2 receptors are the predominant cholinoceptors present in urinary bladder, but mainly the minor population of M3 receptors mediate its contraction. M2 receptors modulate detrusor contraction by several mechanisms, and may contribute more to contraction of the bladder in pathological states such as bladder denervation or spinal cord injury. Prejunctional inhibitory M2 or M4 receptors and prejunctional facilitatory muscarinic Ml receptors in the bladder have all been reported. In clinical studies, tolterodine, a non-selective muscarinic antagonist, has been reported to be as effective as oxybutynin but inducing less dry mouth. Thus, although it is not certain which antimuscarinic drugs have the better efficacy and tolerability, the non-selective antimuscarinic drugs seem to be better than M3-selective antagonists in their clinical efficacies. However, controlled release, or intravesical, intravaginal, or rectal administrations of oxybutynin have been reported to cause fewer side effects. Darifenacin, a new M3 selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. To verify which antimuscarinic drugs selective for the muscarinic subtypes have the best efficacy and tolerability, comparative clinical trials between M3 selective antagonists and non-selective compounds, such as olterodine, are required in the future.",2002.0,0,0
137,11760779,Tolterodine: an overview.,J Wefer; M C Truss; U Jonas,"Tolterodine has emerged as a new anticholinergic drug to treat detrusor instability in recent years. This substance and its major metabolite DD01 exhibit a favourable effect-to-side-effect ratio for the bladder. Several clinical studies demonstrated the drug's efficacy in reducing the symptoms of an overactive bladder (urgency, urge incontinence and high micturition frequency) and in increasing functional bladder volume. With a clinical effectiveness comparable to oxybutynin, the side effect-profile measures up favourably to oxybutynin. Consequently, though some limitations need to be addressed, tolterodine can be regarded as the drug of first choice to treat overactive bladders in a variety of patient groups: the young (and otherwise healthy), the elderly, as well as in patients with renal and hepatic insufficiency. A new extended release formula of tolterodine has been launched that may improve patients' compliance.",2002.0,0,0
138,11760782,Trospium chloride--an effective drug in the treatment of overactive bladder and detrusor hyperreflexia.,K Höfner; M Oelke; S Machtens; V Grünewald,"Trospium chloride (TCL), a quaternary ammonium derivative of nortropanol, has been evaluated in a number of clinical and pharmacological studies. Selected pharmacological and clinical pharmacokinetic data are discussed as providing a basis for a better interpretation and understanding of the clinical trial results. An overview of the results of 20 clinical trials and post-marketing surveillance studies including more than 10000 patients is presented.",2002.0,0,1
139,11768839,The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.,B Olsson; B M Landgren,"Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel.",2002.0,0,1
140,11794435,Use of potentially inappropriate drugs in nursing homes.,Jyotsna Dhall; E Paul Larrat; Kate L Lapane,"To examine patterns and determine predictors of inappropriate drug use in nursing homes. Retrospective study. One thousand four hundred ninety-two nursing homes in five states. A total of 44,562 residents admitted to nursing homes over 1 year. Frequency of discontinuation and initiation of potentially inappropriate drugs over the first 90 days after admission to a nursing home was calculated. Data were collected using the minimum data set. On admission, 33% of residents were receiving at least one potentially inappropriate drug. After 90 days, the drug was discontinued in 16% of these residents. Of those not receiving a potentially inappropriate drug on admission, one was begun in 18%. Demographic factors and number of drugs taken by patients were associated with the use of potentially inappropriate drugs. CONCLUSIONS; Use of potentially inappropriate drugs was prevalent on admission and at 90 days after admission. Discontinuation was highest among patients with conditions for which potentially safer therapeutic alternatives existed.",2002.0,0,0
141,11813937,Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.,B J O'Brien; R Goeree; L Bernard; A Rosner; T Williamson,"Tolterodine is a novel muscarinic receptor antagonist for the treatment of overactive bladder. The purpose of this study was to examine the cost-effectiveness of tolterodine for patients with urge incontinence (UI) who discontinue initial therapy with oxybutynin in a Canadian setting. We compared 2 treatment strategies for the management of adult patients with UI: (1) generic oxybutynin with no further treatment for patients who discontinue and (2) generic oxybutynin with switch to tolterodine (2 mg BID) for patients who discontinue. We developed a 1-year Markov model (4-week cycle length) with transitions between disease states of normal, mild, moderate, and severe. Transition probabilities over 12 weeks were obtained from randomized trial data, and drug discontinuation rates were obtained from Quebec prescription claims data. Outcome measures were time in ""normal"" health state and quality-adjusted life-years (QALYs) using EuroQol-5D utility scores from a survey of Swedish patients with overactive bladder. Costs to the health care payer and patient out-of-pocket costs (in Canadian dollars) were included. For patients who discontinue oxybutynin, the use of tolterodine is associated with approximately 6 months per year in a normal health or mild disease state, compared with approximately 3 months for those who do not receive further drug therapy after discontinuation. Tolterodine use resulted in an annual additional cost per patient of Can $163. The incremental cost per QALY was Can $9,982 and appeared to be robust to alternative model parameter assumptions. Use of tolterodine in patients with UI who discontinue initial therapy with generic oxybutynin lies within currently accepted benchmarks for cost-effectiveness.",2002.0,0,0
142,11822060,[Continence problems after radical prostatectomy: medical treatment].,U Fontanella; M Castiglioni; A Fonte; F Ostini,"We hypothesized that a benefit can be obtained from both urine storage and urethral resistance after retropubic radical prostatectomy through the induction of artificial erections. From January 1993 to December 2000 we have submitted 127 patients to radical retropubic prostatectomy. According to preoperative bladder behaviour, 59 patients (46.5%) presented voiding disorders, 10 (7.9%) filling disorders, 4 (3.1%) mixed disorders, whereas 54 (42.5%) were asymptomatic. The urethral catheter was removed between the 10th and the 12th postoperative day. Fourteen patients entered a programme of early sexual rehabilitation with intracavernous injection of prostaglandin E1 (ICI) within 7 days from catheter removal. After catheter removal the recovery of urinary continence occurred within 2.2 +/- 2.3 days. At dismissal from the hospital, 8 patients (6.2%) were almost totally incontinent; 2 (1.5%) were still incontinent after a 6-month period; 73 (57.4%) were dismissed with clinical signs of detrusor instability hence treated with anticholinergic drugs such oxybutynin or tolterodine; 3 (2.3%) resulted obstructed after surgery because of stenosis of the anastomosis. Almost all the patients submitted to early sexual rehabilitation referred an improvement of their incontinence after the first injection. The patients who did not begin an early sexual rehabilitation generally recovered from incontinence in a longer time. Our preliminary observations showed that artificial erection PGE1-induced is effective in improving or accelerating post radical prostatectomy incontinence recovery. The results apply also to patients with pre-operatory detrusor instability.",2002.0,0,0
143,11825311,Evidence for the efficacy and safety of tolterodine in the treatment of overactive bladder.,P Abrams,"Overactive bladder (OAB) is a chronic and prevalent condition, the symptoms of which (urinary frequency and urgency, with or without urge incontinence) can exert a profound negative effect on a person's daily life activities. Tolterodine (Detrol in North America and Detrusitol in the rest of the world, Pharmacia), a competitive muscarinic antagonist, is the first agent of this class to be specifically developed for the treatment of OAB. This agent displays in vivo functional selectivity for the bladder over other tissues that contain muscarinic receptors (e.g., salivary glands, eye), which translates into good efficacy and tolerability in patients with OAB (including the elderly). Comparative, randomised, double-blind studies show that tolterodine (administered as immediate-release [IR] tablets 2 mg b.i.d.) is as effective as oxybutynin (5 mg t.i.d.) in improving all of the troublesome symptoms of OAB but with a significantly lower incidence and severity of dry mouth. The advent of a new extended-release (ER) capsule formulation of tolterodine (4 mg) for convenient once-daily treatment builds upon these findings, with significantly improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth relative to the existing IR tablet (2 mg b.i.d.). Tolterodine can therefore be considered a valuable, well-tolerated treatment option for patients with OAB, providing improvements in symptoms that are both clinically meaningful to patients and sustained during long-term treatment.",2002.0,0,0
144,11880062,Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results.,H Schulte-Baukloh; T Michael; J Schobert; T Stolze; H H Knispel,"The established treatment of children with neurogenic bladder consists of the use of anticholinergic drugs, such as oxybutynin and tolterodine, and clean intermittent catheterization four or five times a day. If anticholinergic drugs and clean intermittent catheterization fail, surgery is often necessary. With the intent of avoiding surgery, we investigated the effect of botulinum-A toxin for treating detrusor hyperreflexia in this group of patients. The subjects were 17 children (average age 10.8 years) who had detrusor hyperreflexia and were using clean intermittent catheterization four or five times a day. Urodynamic studies were followed by injection of 85 to 300 U of botulinum-A toxin into 30 to 40 sites in the detrusor muscle. Urodynamic follow-up was done 2 to 4 weeks after injection. The mean reflex volume increased by 112.1%, from 95.00 plus minus 34.54 mL (range 47 to 147) to 201.45 plus minus 68.57 mL (range 77 to 310) (P <0.005). The maximal bladder capacity increased by 56.5%, from 137.53 plus minus 59.96 mL (range 59 to 242) to 215.25 plus minus 96.36 mL (range 60 to 380) (P <0.005). The maximal detrusor pressure decreased by 32.6%, from 58.94 plus minus 32.32 cm H(2)O (range 19 to 149) to 39.75 plus minus 26.12 cm H(2)O (range 7 to 100) (P <0.005). Detrusor compliance increased by 121.6%, from 20.39 plus minus 26.5 mL/cm H(2)O (range 4.5 to 40) to 45.18 plus minus 45.4 mL/cm H(2)O (range 5.3 to 100) (P <0.01). Botulinum-A toxin injection into the hyperreflexive detrusor muscle seems to be very effective and might be a therapeutic alternative to anticholinergic drugs.",2002.0,0,0
145,11880086,Preliminary study of the safety and efficacy of extended-release oxybutynin in children.,Katrin Youdim; Barry A Kogan,"To test the safety and efficacy of extended-release oxybutynin in children with bladder dysfunction. The efficacy of oxybutynin in children has been limited by side effects. A new extended-release formulation of oxybutynin has some benefits versus traditional oxybutynin but has never been evaluated in children. A retrospective study was performed on 25 children who had been treated with extended-release oxybutynin. Fourteen had neurogenic bladder dysfunction and 11 had urinary frequency and urgency and urge incontinence but no neurologic abnormalities. Patients and families were asked to semiquantitatively (0 to 10 grading with 10 = severe) assess the effects of the medication on efficacy, as well as side effects and compliance with medication schedules. All 25 patients had improvement in incontinence and/or voiding dysfunction on extended-release oxybutynin. Twelve (48%) experienced no side effects. Of the 13 who did, 10 complained of dry mouth (grade 4.6 plus minus 0.5), 4 had constipation (grade 5.8 plus minus 1.8), 4 had heat intolerance (grade 5.1 plus minus 0.9), and 3 had drowsiness (grade 5.3 plus minus 2.4). Of patients previously treated with oxybutynin, the extended-release oxybutynin was equally or more efficacious and had the same or fewer side effects, especially less dry mouth. Families reported much better patient compliance with the medication regimen using extended-release oxybutynin compared with oxybutynin. Patient and family satisfaction was very high, and 21 of 25 have continued using the medication. Extended-release oxybutynin is safe and efficacious in children. In this preliminary evaluation, it had benefits over traditional, immediate-release oxybutynin.",2002.0,0,0
146,11927295,Efficacy of desmopressin in treatment of refractory nocturia in patients older than 65 years.,Hann Chorng Kuo,"To evaluate the efficacy of desmopressin treatment in patients 65 years old and older with nocturia and to determine whether baseline urodynamic characteristics influenced the outcome of treatment. Patients with nocturia three or more times a night and nocturnal polyuria refractory to medication were treated with oral desmopressin 0.1 mg at bedtime for 4 weeks. Data from urodynamic studies and a voiding diary, nocturnal urine volume, urine specific gravity, serum sodium and potassium level, and quality of life index were measured at baseline, 4 weeks, and 4 weeks after discontinuation of treatment. A total of 30 patients (25 men and 5 women) were enrolled in the study. The mean age was 75.4 +/- 6.6 years. Five patients (16.7%) reported side effects, including hyponatremia in one. Twenty patients (66.7%) reported a good response with both reduced nocturnal frequency (5.2 +/- 1.16 times versus 2.24 +/- 1.12 times a night, P = 0.000) and urine volume (955.6 +/- 255.9 mL versus 522.8 +/- 210.5 mL, P <0.0001). Two patients (6.7%) had improved nocturnal frequency, and 3 patients (10%) reported no effect at all. After discontinuing the medication for 4 weeks, 13 patients (52%) had improved symptoms compared with baseline and 6 (24%) remained at their post-treatment frequency of nocturia. Urodynamic studies revealed that 15 patients had detrusor instability and 17 had a cystometric capacity of 250 mL or less. No significant difference was found in the success rate relative to the urodynamic results. Desmopressin is safe and effective in the treatment of severe nocturia in patients 65 years old and older.",2002.0,0,0
147,11934349,Oxybutynin chloride: alterations in drug delivery and improved therapeutic index.,Roger Dmochowski; Sherron Kell; David Staskin,"Oxybutynin chloride (Ditropan, Alza) is widely regarded as the most efficient antimuscarinic agent for the treatment of bladder detrusor dysfunction resulting in urinary urgency, frequency and urge incontinence. Oxybutynin metabolism occurs primarily in the proximal gastrointestinal tract and the hepatic circulation and is mediated by the cytochrome P450 3A4 isozyme. The major degradation products are desethyloxybutynin, which possesses pharmacological activity, and phenylcyclohexylglycolic acid, which is metabolically inert. A major limitation to long-term compliance with immediate-release oxybutynin remains the necessity for twice- or thrice-daily dosing regimens to provide sustained pharmacological efficacy. Side effects induced by cytochrome P450 metabolism of oxybutynin into the primary metabolite desethyloxybutynin within the gut wall substantially affect the tolerability of the compound within the individual. The oral osmotic delivery system provides unique advantages for drug delivery and substantially alters the tolerability profile of the oxybutynin chloride compound. This extended-release formulation consists of a two component core encapsulated by a semi-permeable membrane. The osmotic gradient between the surrounding environment and the inner core of the delivery system remains constant and water absorption within the capsule is controlled by the semipermeable membrane causing a controlled release of drug, which is sustained over 24 h. Herein are reviewed the various pre- and post-approval trials which have documented the overall therapeutic index of the oral osmotic oxybutynin (Ortho-McNeil Pharmaceuticals). Subsequent post-market surveillance issues are reviewed as are new developments in oxybutynin delivery.",2003.0,0,1
148,11973763,Assessment and conservative management of the neuropathic bladder.,A M K Rickwood,"The etiologies and forms of congenital neuropathic bladder are described: contractile (25%), acontractile (15%), and intermediate (60%). The terminology relating to neuropathic bladder is defined and the principles of bladder management are highlighted: (1) must achieve a bladder that can fill at low pressure, (2) must achieve a bladder that can store urine at low pressure, (3) must achieve sphincter resistance that is sufficient to allow urine storage, and (4) must put in place a mechanism of achieving complete voluntary bladder emptying. The approach to investigation is set out in a logical sequence, and the methods of achieving the goals highlighted above are described. All of this is put in the context of managing the handicapped patient as a whole. It also is stressed that the aim is not just to achieve continence but perhaps even more importantly to protect renal function.",2002.0,0,0
149,11978158,,,,,0,1
150,11998091,Treatments for overactive bladder.,M Newton; J H Kosier; D Smith,,2002.0,0,0
151,11999467,"Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review.",Eric S Rovner; Alan J Wein,"Overactive bladder (OAB) is a chronic condition that often requires long-term treatment to maintain control of symptoms. A range of therapeutic options are available; however, antimuscarinic agents form the mainstay of treatment. Of these agents, tolterodine and oxybutynin are the most widely used. It is well documented that the immediate-release (IR) formulations of these agents have equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates a more favorable tolerability profile, particularly in terms of the frequency and severity of dry mouth. Due to the development of novel drug delivery systems, extended-release (ER) formulations of both oxybutynin and tolterodine are now available, permitting once-daily dosing. The convenience of once-daily dosing of antimuscarinic agents would be expected to improve patient compliance and further relieve the symptoms of OAB. Clinical studies with the ER formulations of tolterodine and oxybutynin demonstrate potential clinical advantages over their respective IR forms in terms of either efficacy or tolerability or both, although the therapeutic index of tolterodine ER appears to show a greater advantage over its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the two ER agents have not been compared directly in a head-to-head clinical study. Overall, available clinical data suggest that the newly developed ER formulation of tolterodine represents a significant therapeutic advancement in the treatment of OAB.",2002.0,0,0
152,12001821,Tolterodine: selectivity for the urinary bladder over the eye (as measured by visual accommodation) in healthy volunteers.,Christopher R Chapple; Lisbeth Nilvebrant,"Tolterodine exhibits a favourable selectivity for the urinary bladder over salivary glands in vivo, in the anaesthetised cat, whereas oxybutynin shows the opposite selectivity profile in this model. This study further evaluated the selectivity profiles of tolterodine and oxybutynin by comparing the effects on bladder function and visual accommodation in the same individuals. In a double-blind, randomised, four-way crossover study, 16 healthy volunteers received single oral doses of tolterodine 5 mg and oxybutynin 2.5, 5 and 7.5 mg. Voiding parameters were assessed for 12 hours post-dose, along with visual accommodation (near point of vision) at regular intervals. A dose-dependent increase in maximum bladder capacity was observed for oxybutynin [2.5 mg (+35%), 5 mg (+45%) and 7.5 mg (%)]. The effect of tolterodine 5 mg on bladder capacity was approximately twice (+93%) that seen after oxybutynin 5 mg and the onset of the effect was more rapid with tolterodine. Effects on visual accommodation were also dose-dependent for oxybutynin (maximum changes in near point of vision were 13%, 20% and 29%, respectively). The maximum change observed after tolterodine 5 mg was the same as after oxybutynin 5 mg (i.e. 20%). Tolterodine seems to exhibit selectivity for the bladder over the eye. Therefore, these results suggest that the normal dosage of tolterodine (2 mg twice daily) may have less effect on visual accommodation than the equivalent dosage of oxybutynin (5 mg three times daily) in patients with an overactive bladder.",2002.0,0,0
153,12010242,A long-term follow-up of autoaugmentation in myelodysplastic children.,A Marte; D Di Meglio; A M Cotrufo; G Di Iorio; M De Pasquale; A Vessella,"To evaluate the long-term results of patients who underwent bladder autoaugmentation (BA) in whom BA was used to treat a neuropathic bladder secondary to myelomeningocele, and who presented with a high-pressure/poorly compliant bladder. Eleven patients (eight girls and three boys, mean age 12.8 years, mean follow-up 6.6 years) were selected who had undergone BA between June 1991 and June 1994. At surgery, the patients had a poorly compliant bladder with a mean leak point volume (LPV) of 94 mL and a mean leak point pressure (LPP) of 58 cmH2O. None of the patients had vesico-ureteric reflux (VUR) at BA; five with grade III or IV VUR had undergone endoscopic correction in a day-surgery procedure using a suburethral collagen injection 1-3 weeks before BA. The patients were evaluated using clinical, urodynamic, radiological and endoscopic assessments. The LPV, LPP and safe bladder capacity (SBC, the cystometric volume at an intravesical pressure of 40 cmH2O) were recorded. At 1 year after surgery the mean LPV was 297 mL; none of the patients had VUR. The most recent mean LPV was 198 mL and the SBC 167 mL. The mean LPP remained stable at 60 cmH2O. At the last follow-up four patients had recurrent uni- or bilateral grade III-V VUR. At endoscopy the 'augmented' bladder portion had a smooth surface, compared with the grossly trabeculated lower half. From this finding all patients on clean intermittent catheterization were treated with oral oxybutynin. Some patients reported slightly less abdominal pain at maximum bladder volume; four needed pads to treat intermittent incontinence. On voiding cysto-urethrography, one patient had an hourglass-shaped bladder. Five patients recently underwent ileocystoplasty because of recurrent urinary tract infection, high-grade VUR and incontinence. These results do not justify the routine use of BA in hypertonic/poorly compliant bladders secondary to myelomeningocele. The mean follow-up of 6.6 years showed that this procedure failed in seven of 11 patients. Further studies might be able to identify subgroups in which this approach may be more appropriate.",2002.0,0,0
154,12017406,"A multicenter, prospective, open-label study of tolterodine extended-release 4 mg for overactive bladder: the speed of onset of therapeutic assessment trial (STAT).",Paul Siami; Larry S Seidman; Daniel Lama,"Antimuscarinic agents are the primary treatment for overactive bladder (OAB), but there is a lack of information regarding when maximum symptom relief and maximum perceived patient benefit occur. This study assessed the speed of onset of therapeutic benefit with tolterodine extended-release (ER) 4 mg. This 12-week, multicenter, prospective, open-label study enrolled patients with OAB who either had received no previous pharmacologic treatment for OAB (drug naive) or were receiving such treatment at enrollment (previously treated). Efficacy was assessed at 1, 4, and 12 weeks using a micturition diary and measures of patients' and physicians' perceptions of improvement. Safety was assessed in terms of adverse events and study withdrawals. The intent-to-treat population included 1138 patients (302 men, 836 women; 88.4% white; age range, 18-91 years), 735 drug naive and 403 receiving treatment for OAB at enrollment. After 1 week, tolterodine ER 4 mg had produced a significant improvement in all efficacy variables in both groups of patients (P < 0.01); 72% of the maximum effect on urge incontinence was observed in both groups; and 84.7% of drug-naive patients and 83.6% of previously treated patients perceived a benefit from treatment. After 4 weeks, drug-naive and previously treated patients reported a respective 93% and 100% of the maximum effect on episodes of urge incontinence. Tolterodine was well tolerated, with dry mouth (mostly mild) the most commonly reported adverse event (15.5% in each group). The 330 (81.9%) patients who had reported unacceptable efficacy and the 87 (21.6%) patients who had reported unacceptable tolerability of previous OAB treatment responded favorably to tolterodine ER 4 mg. Tolterodine ER 4 mg was effective and well tolerated in both drug-naive and previously treated patients with OAB. More than 80% of patients reported benefit from treatment after 1 week, but maximum symptom relief was achieved with longer treatment.",2002.0,1,1
155,12028164,"Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients.",Norman R Zinner; Anders Mattiasson; Stuart L Stanton,"To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients. A 12-week double-blind, placebo-controlled clinical trial. An international study conducted at 167 medical centers. One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency. Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks. Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older. Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87). The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age.",2002.0,1,1
156,12028165,Urodynamic changes associated with behavioral and drug treatment of urge incontinence in older women.,Patricia S Goode; Kathryn L Burgio; Julie L Locher; Mary G Umlauf; L Keith Lloyd; David L Roth,"To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence. Randomized, double-blinded, placebo-controlled, clinical trial. Eligible patients were stratified according to type of incontinence (urge only vs mixed urge and stress) and severity of incontinence (frequency of accidents as documented in bladder diary). University-based outpatient geriatric medicine clinic. One hundred five ambulatory, nondemented, community-dwelling women; mean age 67.0 (range 55-91); 98% white, 2% African American. Four sessions (over 8 weeks) of biofeedback-assisted behavioral training, drug treatment with individually-titrated oxybutynin chloride, or a placebo control condition. Two-channel cystometry was performed to determine threshold volumes for first desire to void (FDV), strong desire to void (SDV), bladder capacity, and the volume at which detrusor instability (DI) or leakage occurred, before randomization and after completion of treatment. Two-week bladder diaries were used before and after treatment to document episodes of incontinence and voiding frequency. Bladder capacity increased by 68.9 mL in the oxybutynin group (P <.001) and 17.3 mL in the behavior group and decreased 6.0 mL in the control group. SDV increased 69.9 mL in the oxybutynin group (P <.001), 40.5 in the behavior group (P <.05), and 7.8 mL in the control group. FDV increased by 44.4 mL in the oxybutynin group (P <.001), 18.8 mL in the behavior group, and 8.9 mL in the control group. One of seven patients who presented with DI (12.0%) resolved in the behavior group, seven of eight (87.5%) resolved in the oxybutynin group, and seven of 12 (58.3%) resolved in the control group. These differences were not statistically significant. Voiding frequency was significantly reduced after treatment in both the behavior and the oxybutynin group. Behavioral training resulted in a mean 82.3% reduction in frequency of accidents, oxybutynin (final doses 2.5 mg daily to 5 mg three times a day) resulted in a mean 78.3% reduction, and the control condition resulted in a mean 51.5% reduction (P =.002). Although oxybutynin and behavioral treatment were both effective, and oxybutynin increased SDV and bladder capacity, the structural equation modeling did not demonstrate that the clinical improvement was mediated through the effects of these treatments on urodynamic or voiding frequency measures. Studies using more-complex urodynamics and studies with larger sample sizes are needed to better characterize changes in bladder function and explore other urodynamic changes that may accompany treatment. In addition, other factors, both physiological and behavioral, need to be explored as mechanisms by which conservative therapies improve urge incontinence.",2002.0,1,1
157,12028169,Use of anticholinergic medications by older adults with dementia.,Catherine M Roe; Michael J Anderson; Barney Spivack,"To compare the prevalence of anticholinergic use in older adults with probable dementia with that of a matched comparison group of older adults who were unlikely to have dementia and to examine the extent to which patients taking donepezil concomitantly use anticholinergic medications. Retrospective study. Community-based older adults receiving medications through a pharmacy benefit management company. Eight hundred thirty-six patients aged 65 and older. Patients taking donepezil (n = 418) constituted the treatment group. Patients not taking donepezil (n = 418) constituted the comparison group. Each treatment group member was matched with a comparison group member on the basis of age, sex, and number of drugs taken for chronic conditions. The prevalence of anticholinergic use was compared in the treatment and comparison groups over a 3- to 12-month follow-up period using pharmacy claims data. The proportion of follow-up period days that treatment group members concomitantly used donepezil and anticholinergics was also examined. Older adults with probable dementia were more likely to use anticholinergics than matched comparison group patients (33.0% vs 23.4%; P =.001). Of treatment group members receiving anticholinergics, 26.1% used multiple anticholinergic medications. Treatment group members who received anticholinergics used those drugs concomitantly with donepezil on a mean of 28.4% of follow-up period days. Community-based, commercially insured, older adults with probable dementia are more likely to take anticholinergics than matched controls. Patients taking donepezil frequently use an anticholinergic medication concomitantly. This study suggests that prescribing for older adults with dementia could be improved, especially if cognitive enhancing agents are being considered.",2002.0,0,0
158,12028232,Incorrect assumption regarding the mechanism of action of flavoxate.,Irina Pikovskaya,,2002.0,0,0
159,12028256,Urinary antispasmodic use and the risks of ventricular arrhythmia and sudden death in older patients.,Philip S Wang; Raisa Levin; Sean Z Zhao; Jerry Avorn,"The introduction of new medications to treat overactive bladder has resulted in a significant increase in the number of individuals with this condition who use medications for symptoms. Formal epidemiological studies of the safety of these medications in typical patient populations are lacking, particularly studies of serious events. We sought to determine whether the use of urinary antispasmodics increases the risk of ventricular arrhythmias or sudden death. Retrospective cohort study. Retrospective analysis of data of participants in community, hospital or nursing home setting. Fourteen thousand six hundred thirty-eight subjects with a diagnosis of urinary incontinence made between January 1, 1991, and June 30, 1995; all were aged 65 and older and enrolled in Medicare and Medicaid or the Pharmacy Assistance for the Aged and Disabled programs of New Jersey. Filled prescriptions for oxybutynin (Ditropan), flavoxate (Urispas), hyoscyamine (Cystospas), and hyoscyamine sulfate (Cystospas-M) were used to define days of exposure to these drugs. We also identified all use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors, and their concurrent use, to serve as a positive control exposure. Two outcomes were then defined: a new diagnosis of ventricular arrhythmia combined with initiation of an antiarrhythmic medication and sudden death. Other covariates, including clinical, demographic, medication use, and healthcare utilization variables, were also assessed. Adjusted risk ratios of ventricular arrhythmia and sudden death were derived from multivariable Cox proportional hazards models. There was no significant association between periods of use of urinary antispasmodics and the development of ventricular arrhythmias (adjusted risk ratio (RR) = 1.23, 95 confidence interval (CI) = 0.87-1.75) or sudden death (adjusted RR = 0.70, 95% CI = 0.28-1.74). A significantly increased risk of ventricular arrhythmia was observed for the positive control regimen, concurrent use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors (adjusted RR = 5.47; 95% CI = 1.34-22.26), but not for use of either drug group alone. Concurrent use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors was also associated with a significant increase in the risk of sudden death (adjusted RR = 21.50, 95% CI = 5.23-88.37). Other variables significantly associated with ventricular arrhythmia included ischemic heart disease and congestive heart failure, whereas nursing home use before the index date was associated with a decreased likelihood of receiving a diagnosis of and treatment for ventricular arrhythmia. Other variables significantly associated with sudden death included male gender, black race, and congestive heart failure. Antimuscarinic urinary antispasmodics available before 1996 were not associated with an increased risk of ventricular arrhythmias and sudden death. Additional study will be required to confirm these results, exclude the possibility of unmeasured confounders contributing to any lack of an observed relationship, and extend these findings to newer agents such as tolterodine.",2002.0,1,1
160,12030634,Overactive bladder patients and role of the pharmacist.,Kate Stewart; William F McGhan; Tracy Offerdahl; Ron Corey,"To summarize the prevalence, quality of life (QOL) implications, cost of illness, and pharmacotherapy of overactive bladder (OAB), and to describe the pharmacist's role in the management of patients with OAB. Articles published between 1990 and 2001 identified through a MEDLINE search using the terms overactive bladder, unstable bladder, urinary incontinence, prevalence, cost of illness, quality of life, drug therapy, pharmacist, and pharmacy in various combinations. All studies providing information on OAB or urinary incontinence were retrieved. By the authors. Published prevalence and cost studies focus primarily on urinary incontinence, which is only one possible symptom of OAB. Reported prevalence rates of urge and mixed incontinence in the United States range from 3% to 8% and 5% to 37%, respectively, and the highest prevalence has been found in geriatric and psychogeriatric populations. Associated costs are substantial. Total costs of OAB in the United States were estimated to be $12.6 billion in 2000. Patients with OAB score lower than the general population in QOL assessments. All aspects of QOL can be compromised by OAB, as physical, social, occupational, domestic, and sexual activities are often limited in OAB patients. The pharmacist is instrumental in improving an individual's QOL through ensuring safe and effective treatment for OAB. Oxybutynin and tolterodine (Detrol-Pharmacia) have been the mainstays of pharmacotherapy for OAB, but frequent adverse effects (including dry mouth) often prevent patients from adhering to treatment. Tolterodine, now available in a new long-acting formulation, has been proven safe and efficacious in the treatment of OAB, with fewer adverse effects and better tolerability than existing agents. Pharmacists can play an active role in helping identify and recommending interventions for OAB that can ultimately improve an individual's QOL.",2002.0,0,0
161,12045724,Sexual and urological dysfunction in multiple sclerosis: better understanding and improved therapies.,Ranan DasGupta; Clare J Fowler,"The fundamental strategy in treating multiple sclerosis patients with unstable bladders involves a combination of suppressing urgency and ensuring effective urinary drainage. Anti-cholinergics remain the first-line treatment, but alternative therapies are undergoing clinical trials. With a range of new pro-erectile oral medications available, interest has grown in treatment of multiple sclerosis-related erectile failure. Female sexual dysfunction is also now gaining some attention, with new classification criteria and methods for assessing and treating these patients.",2002.0,0,0
162,12047983,Treatment interventions for Parkinson's disease: an evidence based assessment.,Olivier Rascol; Christopher Goetz; William Koller; Werner Poewe; Cristina Sampaio,"We did a systematic review, with a uniform method of assessment of efficacy and safety, to assess the different interventions available for the management of Parkinson's disease (drugs, surgical interventions, and physical treatments) with respect to the following indications: prevention of disease progression, symptomatic treatment of motor features (parkinsonism), symptomatic control of motor complications, prevention of motor complications, and symptomatic treatment of non-motor features. Our aim was not to define practice guidelines, but rather to improve clinicians' knowledge of the presently available published clinical evidence, based mainly on randomised controlled trials. We hope that our review will help doctors to incorporate this background into their own decision-making strategy to make appropriate choices with respect to the treatment of individual patients with Parkinson's disease.",2002.0,0,0
163,12060436,Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder.,Jeong Gu Lee; Jae Yup Hong; Myung-Soo Choo; Hun Young Kwon; Do Young Chung; Kyu Sung Lee; Ji Youl Lee; Tack Lee,"This double-blind, multicenter study compared the efficacy and tolerability of tolterodine (Pharmacia, Los Angeles, USA) with that of oxybutynin (Alza, Palo Alto, USA) in Asian patients with overactive bladder. Two-hundred-and-twenty-eight adults with overactive bladder symptoms were randomized to receive tolterodine 2 mg twice daily (bid) (n = 112) or oxybutynin 5 mg bid (n = 116). After 8 weeks' treatment, changes in micturition diary variables, patients' perception of treatment benefit, and tolerability endpoints were determined. The mean (+/- SD) number of micturitions/24 h decreased by 2.6 +/- 2.9 (-21%) with tolterodine and 1.8 +/- 4.2 (-15%) with oxybutynin (both P = 0.0001 vs baseline). The mean number of incontinence episodes/24 h decreased by 2.2 +/- 2.3 (-85%) in the tolterodine group and by 1.4 +/- 1.8 (-58%) in the oxybutynin group (both P = 0.0001 vs baseline). Patient perception of treatment benefit was over 70% in each treatment group. Adverse events were significantly lower in the tolterodine group compared with oxybutynin-treated patients (55% vs 82%; P = 0.001). Dry mouth was reported by significantly fewer patients on tolterodine, compared with oxybutynin (35% vs 63%; P = 0.001) and withdrawals due to adverse events were lower in the tolterodine group than with those treated with oxybutynin (10% vs 16%). There were no safety concerns. Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the treatment of Asian patients with overactive bladder, and shows significantly better tolerability. This may enhance compliance during long-term treatment.",2003.0,1,1
164,12074774,"Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder.",K Kreder; C Mayne; U Jonas,"The objective of the present study was to examine the long-term safety, tolerability and efficacy of tolterodine extended-release (ER) in patients who had completed 12 weeks' treatment in a randomised, double-blind study comparing tolterodine ER 4 mg once daily (qd), tolterodine immediate-release (IR) 2mg twice daily and placebo. Of the 1377 patients completing the 12-week study, a total of 1077 (78%) chose to continue with 12 months' open-label treatment with tolterodine ER 4 mg once daily, irrespective of their previous treatment. Safety was assessed after 3, 6, 9 and 12 months' treatment in the study. Efficacy was evaluated from micturition diary variables and patients' perception of bladder condition and urgency following 3 and 12 months' treatment. 71% of patients completed the 12-month study. Tolterodine ER was safe and well tolerated. Adverse events of the general (14.5%), autonomic (13.2%), gastrointestinal (11.4%), respiratory (9.8%) and urinary (9.1%) systems were the most frequently reported. Dry mouth was the most common event, occurring in 12.9% of patients, and was generally mild in severity. Other adverse events occurred in less than 5% of patients. There was no increase in the frequency of adverse events with long-term relative to short-term treatment. The efficacy of tolterodine was maintained over the 12-month treatment period; relative to baseline there were reductions in the number of incontinence episodes per week (median change -83%) and micturitions per 24 hours (median change -21%) and an increase in volume voided (median change +25%) after 12 months' treatment. An improvement in patient perception of their bladder condition was found in 75% of patients completing the study, and 51% had an improvement in patient perception of urgency. Tolterodine ER 4mg qd displayed a favourable safety, tolerability and efficacy profile during 12 months' treatment of patients with overactive bladder.",2002.0,1,1
165,12083983,Current pharmacotherapeutic strategies for overactive bladder.,Alan D Garely; Lara J Burrows,"Overactive bladder (OAB) is a chronic, distressing condition characterised by symptoms of urgency (sudden overwhelming urge to urinate) and frequency (urinating more than eight times daily), with or without urge urinary incontinence (sudden involuntary loss of urine). It affects millions of people of all ages and both sexes world wide, with greater prevalence in women and the elderly. The treatment of OAB is aimed at reducing debilitating symptoms, which have a significant effect on all aspects of an individual's quality of life, including social, domestic, psychological, occupational, physical and sexual functioning. Anticholinergic agents are currently recommended as first-line therapy for OAB. Their use results in significant clinical improvement in patients, although a lack of selectivity for receptors in the bladder may lead to troublesome side effects, including dry mouth, blurred vision, somnolence, dizziness and constipation. Recent research efforts have focused on developing drugs with a reduced propensity for causing these problems. Of the available anticholinergic agents, oxybutynin and tolterodine are the most widely used to treat OAB. Studies directly comparing tolterodine immediate-release (IR) with oxybutynin IR have shown that the two agents have similar efficacy. However, tolterodine IR is significantly better tolerated, particularly with respect to the incidence and severity of dry mouth. An extended-release formulation of tolterodine (4 mg capsules) has recently been developed to allow for once-daily dosing. In addition to greater convenience, tolterodine extended-release has shown enhanced efficacy and tolerability compared with tolterodine IR.",2002.0,0,0
166,12110086,Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors.,Keith R Edwards; Judy T O'Connor,,2002.0,0,0
167,12123469,The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro.,R Chess-Williams; C R Chapple; T Yamanishi; K Yasuda; D J Sellers,"1 The objective was to determine the role of muscarinic receptor subtypes in mediating contraction of the human detrusor smooth muscle in vitro. 2 Contractile responses of human detrusor muscle strips to carbachol were obtained in the absence and presence of a range of muscarinic antagonists (pirenzepine, methoctramine, 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP), tropicamide, oxybutynin and tolterodine). Affinity estimates (pKB values) were calculated for the antagonists and correlated with values at the cloned muscarinic receptor subtypes quoted in the literature. 3 Pirenzepine, methoctramine and tropicamide drugs that have high affinities at M1, M2 and M4-receptors, respectively, all had low affinities on the human detrusor (pKB values of 6.8, 6.9 and 6.5, respectively), whilst the M3-selective antagonist 4-DAMP had a high affinity (9.5). Schild plots for all four antagonists had slopes of unity indicating an action at a single receptor. Oxybutynin and tolterodine also acted as competitive antagonists with affinity estimates of 7.6 and 8.1, respectively. 4 When the antagonist affinities obtained on the bladder were plotted against the values published for these antagonists at the cloned muscarinic receptor subtypes, the best correlations were obtained for the m3- and m5-muscarinic receptor subtypes. 5 These data suggest that direct contractile responses of the human detrusor muscle to muscarinic receptor stimulation in vitro are mediated solely via the M3-muscarinic receptor subtype with no contribution from the major M2-receptor population.",2002.0,0,0
168,12131314,,,,,0,1
169,12147560,Medical therapy for the overactive bladder in the elderly.,Adrian Wagg; Maurice Cohen,"The overactive bladder is the commonest underlying bladder disorder causing urinary incontinence in elderly people. Management of the condition relies upon a holistic assessment of the problem, lifestyle adjustment, behavioural management and drug therapy. The majority of currently available drugs rely on their anti-muscarinic properties for efficacy. Both behavioural techniques and drug therapy are effective in treatment of the elderly and each modality has a particular role to play in successful treatment and maintenance of this condition.",2002.0,0,0
170,12153373,"Inappropriate drug prescribing in home-dwelling, elderly patients: a population-based survey.",Kaisu H Pitkala; Timo E Strandberg; Reijo S Tilvis,"In 1997, a US expert panel developed explicit criteria on potentially inappropriate drugs for the general elderly population. To investigate the proportion of inappropriate medications among home-dwelling, elderly patients in Helsinki, Finland, between November 1, 1998, and March 31, 1999. A cross-sectional mail survey was sent to a random sample of 3921 elderly urban residents aged 75, 80, 85, 90, and 95 years. Of these, 3219 were home dwellers. Prevalence of potentially inappropriate drugs and prevalence of drugs considered inappropriate related to 15 common medical conditions according to recommendations given by the expert panel in 1997. The response rate was 78%. Of the respondents, 12.5%, 1.3%, and 0.2% were taking at least 1, 2, or 3 inappropriate drugs, respectively. The most prevalent inappropriate drugs were dipyridamole (3.6%), long-acting benzodiazepines (2.6%), amitriptyline hydrochloride (1.6%), ergot mesyloids (1.6%), muscle relaxants (1.2%), and meprobamate (1.1%). Use of medications considered inappropriate with certain medical conditions was higher: 27.2% of patients with chronic obstructive pulmonary disease were taking beta-blockers and 19.3% used sedatives. Of diabetic individuals taking oral hypoglycemics or insulin, 32.5% were taking a concomitant beta-blocker. Of those with a peripheral vascular disease, 37.9% were taking beta-blockers. However, two thirds of all these patient groups had concomitant coronary heart disease. Compared with previous surveys, the use of inappropriate medications in our home-dwelling, elderly population is conspicuously low. In contrast, use of certain drugs considered inappropriate with different medical conditions was relatively high. However, the inappropriateness of the latter treatments may be questioned in individual patients.",2002.0,0,0
171,12175392,A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder.,H Y Leung; S K Yip; C Cheon; Y S Liu; J Lau; H K Wong; K H Chung,"Objective To compare the tolerability and clinical efficacy of tolterodine and oxybutynin in the treatment of Hong Kong Chinese women with an overactive bladder. Patients and methods A randomized controlled trial was conducted at two urogynaecology centres in Hong Kong. In all, 106 women with urodynamically confirmed detrusor instability were recruited. Baseline severity assessments included a visual analogue scale (VAS), urinary diary and urinary pad-test. The women were randomized to receive either oral tolterodine 2 mg or oxybutynin 5 mg twice daily for 10 weeks. Treatment responses were assessed at 4 and 10 weeks using the VAS and urinary diary. Treatment tolerability was assessed at baseline, 4 and 10 weeks using the Xerostomia Questionnaire. A urinary pad-test was repeated at 10 weeks. Results The perceived change from baseline VAS was better in the tolterodine than the oxybutynin group after 10 weeks of treatment (per-protocol analysis, P = 0.043). The two drugs were effective in reducing the symptoms of frequency (P < 0.001). Tolterodine was significantly better than oxybutynin in reducing urinary leakage (urinary pad-test; median change - 5.00 g vs 0 g, P = 0.019). Both drugs caused a significant worsening of dry mouth (overall dryness, P < 0.005; discomfort, P < 0.005; sleep, P = 0.021; speaking, P = 0.045; swallowing, P = 0.004; and liquid consumption, P = 0.017). Conclusions Both oxybutynin and tolterodine were effective in ameliorating the severity of the symptoms of detrusor instability. Tolterodine was better than oxybutynin in both subjective and objective outcome measures, but both drugs caused similar worsening of dry mouth that may limit the tolerability of these medications.",2002.0,1,1
172,12187215,Does gender or age affect the efficacy and safety of tolterodine?,Martin C Michel; Tim Schneider; Susanne Krege; Mark Goepel,"We compared the importance of patient age and gender relative to the intensity of baseline symptoms of overactive bladder in the therapeutic response to the muscarinic receptor antagonist tolterodine. Data from an open label, observational study of 2,250 patients with overactive bladder treated for 12 weeks with tolterodine were analyzed for alterations in frequency, urgency and urge incontinence, and for global efficacy and tolerability using logistic regression analysis, stratifying for gender, age, baseline symptom intensity and tolterodine dose. Gender or tolterodine dose were not consistently associated with altered treatment efficacy. Greater age was associated with a slight but statistically significant decrease in treatment efficacy. Patients with great baseline symptom intensity had greater treatment associated improvement but a lesser chance to become symptom-free. Even with a large number of patients no statistically significant gender or age associated alterations in the tolerability of tolterodine treatment were detected. The extent of the therapeutic response to tolterodine is largely determined by the extent of baseline symptoms. While gender does not affect the efficacy or tolerability of tolterodine in a clinically relevant manner, advanced age is associated with a slight decrease in efficacy but not in tolerability.",2002.0,1,1
173,12212758,The potential of pill splitting to achieve cost savings.,Randall S Stafford; David C Radley,"To present a methodology for identifying specific medications for which pill splitting is clinically appropriate and cost saving, to present data from a commercial managed care population on current pill-splitting practices, and to estimate additional cost savings from extended use of this strategy. Retrospective pharmacy claims analysis. Pharmacy claims data from a commercial managed care health plan covering 19,000 lives and national drug data were used to compile a list of frequently prescribed medications. Excluding medications in which packaging, formulation, and potential adverse pharmacologic outcomes prohibited splitting, we performed a cost analysis of medications amenable to splitting. Eleven medications amenable to pill splitting were identified based on potential cost savings and clinical appropriateness: clonazepam, doxazosin, atorvastatin, pravastatin, citalopram, sertraline, paroxetine, lisinopril, nefazadone, olanzapine, and sildenafil. For these medications, pill splitting is currently infrequent, accounting for annual savings of $6200 (or $0.03 per member per month), just 2% of the potential $259,500 (or $1.14 per member per month) that more comprehensive pill-splitting practices could save annually. Pill splitting can be a cost-saving practice when implemented judiciously using drug- and patient-specific criteria aimed at clinical safety, although this strategy is used infrequently.",2002.0,0,0
174,12231388,"Characterization of a new muscarinic receptor antagonist PNU-171990 in guinea pig, cat and human smooth muscle.",Ali-Reza Modiri; Mervi Vasänge; Peteris Alberts; Sukhwinder S Jossan; Staffan Sundquist; Per-Göran Gillberg,"The present study was done to characterize a new compound, PNU-171990, 2-diisopropyl aminoethyl 1-phenylcyclopentane carboxylate hydrochloride, with functional smooth muscle selectivity at least as high as tolterodine. In vitro homogenates of guinea pig cerebral cortex, parotid gland, heart, urinary bladder, and Chinese hamster ovary (CHO) cells expressing human muscarinic m(1)-m(5) receptors PNU-171990 did not show selectivity for any subtype (pK(i), 7.72-8.64). PNU-171990 caused a parallel shift in the concentration-response curve for carbachol-induced contraction of smooth muscle from guinea pig bladder (pK(B), 7.65), guinea pig ileum (pK(B), 8.48), and human ileum (pK(B), 7.10). In vivo PNU-171990 inhibited urinary bladder contraction with a significantly lower ID(50) than on the salivary secretion (206 and 706 nmol/kg, respectively, P<0.05). In conclusion, PNU-171990 is a competitive and potent muscarinic receptor antagonist in vitro with a numerically better selectivity ratio for the bladder contraction over salivation in vivo than tolterodine.",2003.0,0,0
175,12234085,Pharmacologic options for the management of multiple sclerosis symptoms.,Randall T Schapiro,"Multiple sclerosis (MS) is a disease with a wide-ranging impact on physical functioning. Although pharmacotherapy plays an indispensable role in the management of MS symptoms, optimal disease management requires a multidisciplinary approach that combines medication, rehabilitation, and patient education. Successful control of symptoms is critical to quality of life for MS patients. Immunomodulating drugs provide a means of controlling the underlying disease process, but they are not a cure. This places responsibility on health care providers to control a patient's MS-related symptoms to limit disability and delay impairment in the activities of daily living. Owing to the importance of symptom control, comprehensive patient evaluations should be performed at regular intervals to determine the extent of neurological damage and disease progression and to address changing patient needs. The goal of interventions should be not only to treat the primary and secondary symptoms of MS but also to provide access to the psychosocial support that will help MS patients and their families continue to cope as disease status changes.",2003.0,0,0
176,12236281,Urinary tract infections in adult general practice patients.,Eva Hummers-Pradier; Michael M Kochen,"Urinary tract infections (UTIs) are symptomatic infections of the urinary tract, mainly caused by the bacterium Escherichia coli. One in two women suffers from a UTI at least once in her life. The young and sexually active are particulaly affected, but it is also seen in elderly, postmenopausal women. The likelihood of recurrence is high. Diagnosis is made with regard to typical complaints and the presence of leucocytes and nitrites in the urine. A culture is unnecessary in most cases. Uncomplicated UTI should be distinguished from complicated UTI, which has a risk of severe illness. The treatment of choice--short-term therapy with trimethoprim or nitrofurantoin--is successful in over 80% of the cases. Co-trimoxazol fluoroquinolones or cephalsporins are not considered first-choice drugs. There are indications that general practitioners' (GPs') management of UTI is not always optimal, specifically concerning diagnostic tests, the application of second-choice antibiotics, and the length of prescribed treatment courses. Many points relevant to GPs requirefurther research, such as epidemiology and resistance of urinary pathogens in the community and natural history of UTI, as well as optimal management in elderly or complicated patients and men.",2002.0,0,0
177,12241127,A benefit-risk assessment of extended-release oxybutynin.,Martin C Michel,"Oxybutynin is a muscarinic receptor antagonist, which has been available for a number of years in its original immediate-release (IR) formulation. While oxybutynin IR has proven effective for the treatment of overactive bladder, its extended use can be limited by adverse effects, particularly dry mouth. An extended-release (ER) formulation of oxybutynin based on the OROS system has recently become available, which allows once daily administration. In direct comparison to oxybutynin IR, oxybutynin ER has an increased oral bioavailability for the parent compound oxybutynin which is accompanied by a reduced bioavailability for the active metabolite N-desethyl-oxybutynin. The latter has been implicated in mediating a major part of the adverse effects of oxybutynin treatment. Two double-blind, placebo-controlled, randomised studies in patients with overactive bladder have demonstrated that oxybutynin ER has a similar efficacy as oxybutynin IR but with improved tolerability. This is in line with clinical pharmacological studies demonstrating a smaller impairment of saliva production with oxybutynin ER than with oxybutynin IR. Thus, the ER formulation of oxybutynin maintains the therapeutic benefits and concomitantly improves tolerability.",2002.0,0,0
178,12354340,Treatment of overactive bladder: the Antimuscarinic Clinical Effectiveness Trial.,Rodney A Appell,,2003.0,0,0
179,12354344,,,,,0,0
180,12354576,The subtypes of muscarinic receptors for neurogenic bladder contraction in rats.,Hiroyasu Hirose; Ikuo Aoki; Toshifumi Kimura; Toru Fujikawa; Tomoshige Numazawa; Kaori Sasaki; Masaru Nishikibe; Kazuhito Noguchi,"We evaluated in vivo functional selectivity profiles for muscarinic M(2) and M(3) subtypes of four muscarinic antagonists: Compound A (a novel muscarinic receptor antagonist with M(2)-sparing antagonistic activity), darifenacin, (a muscarinic M(3) receptor antagonist); methoctramine (a muscarinic M(2) receptor antagonist) and tolterodine (a nonselective muscarinic receptor antagonist), and compared the inhibition potency on distention-induced bladder contraction in rats. In an in vivo functional study, Compound A (0.03-10 mg/kg, i.v.) showed antimuscarinic activity with high selectivity for M(3) (salivation) over M(2) (bradycardia) (>100-fold). Darifenacin (0.01-0.3 mg/kg, i.v.) showed only slight selectivity for M(3) over M(2) (3.7-fold). Methoctramine (0.003-1 mg/kg, i.v.) showed the reverse selectivity profile (0.077-fold). Tolterodine (0.003-0.3 mg/kg, i.v.) showed less selectivity (1.2-fold). Compound A at M(3) inhibitory doses (0.1 and 0.3 mg/kg, i.v.) showed inhibition in a distention-induced neurogenic bladder contraction model, and its maximal inhibitory effects were about 60% at an even higher dose (3 mg/kg). Methoctramine at M(2) inhibitory doses (0.03 and 0.1 mg/kg, i.v.) did not significantly affect distention-induced bladder contraction. When tolterodine and darifenacin caused inhibition of distention-induced bladder contraction, its maximal inhibitory effects were similar to that of Compound A. Therefore, these findings suggest that Compound A would be an excellent pharmacological tool to give a better understanding of which subtypes of muscarinic receptors act in bladder function so far, and muscarinic M(3), but not M(2), receptors mainly mediate the cholinergic component of distention-induced bladder contraction.",2003.0,0,0
181,12355297,Office assessment of patient outcome of pharmacologic therapy for urge incontinence.,A C Diokno; J R C Catipay; B W Steinert,"Thirty adult women with urge urinary incontinence were included in this study. After completing the basic evaluation, including a self-administered incontinence questionnaire, patients were treated with a bladder relaxant preparation for 6-8 weeks. At follow-up the incontinence questionnaire and a global assessment of outcome scale were administered. Data were analyzed using the Mann-Whitney and Kruskal-Wallis tests, with a subsequent Tukey's test. After 6-8 weeks of therapy, 63% of patients reported that they were greatly or moderately improved, with a significant mean decrease in their total urge score of 51%. Subjects slightly improved (12%) and unimproved/worse (20%) had no significant change in their mean urge score. Most patients with great or moderate improvement continued with their initial drug treatment. Successful pharmacotherapy for urinary urge incontinence may be assessed by a simple global scale which correlated well with response to the MESA questionnaire. Moderate and greatly improved patients correlated with a 50% mean decrease in urge score and continued their initial drug therapy.",2003.0,0,0
182,12356204,Three screening batteries to detect cognitive impairment in multiple sclerosis.,R L Aupperle; W W Beatty; F de N A P Shelton; S T Gontkovsky,"To compare the sensitivities for detecting cognitive impairment in patients with multiple sclerosis (MS) and administration times of three brief batteries of neuropsychological tests, 64 patients with MS completed the Neuropsychological Screening Battery for Multiple Sclerosis (NPSBMS), the Screening Examination for Cognitive Impairment (SEFCI), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Failure on a particular test was defined as a score below the 5th percentile for healthy controls, and the number of patients who failed at least one or two tests (out of four) was determined for each battery. Both the SEFCI and the NPSBMS identified significantly more patients with impairment than the RBANS, which was no more sensitive than the Mini-Mental State Exam (MMSE). Results were similar at both the one- and two-failed-tests criteria, but there were no significant differences between the SEFCI and the NPSBMS at either failure criterion. Mean administration time was 22.6 min for the SEFCI compared to 31.7 min for the NPSBMS (p < 0.001). Eleven (17%) of the patients refused to attempt the Paced Auditory Serial Addition Test (PASAT), one component of the NPSBMS. For screening patents on a single occasion, the SEFCI is preferred because its administration time is shorter than the NPSBMS.",2003.0,0,0
183,12371799,The newer antimuscarinic drugs: bladder control with less dry mouth.,Rodney A Appell,"Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.",2002.0,0,0
184,12389875,Individualized drug use assessment in the elderly.,Cynthia L Raehl; C A Bond; Tresa Woods; Roland A Patry; Rebecca B Sleeper,"To quantify how seniors' ability to take oral prescription drugs safely may correlate with age, sex, socioeconomic status, education, cognitive impairment, depression, and drug self-management. Cross-sectional study Three retirement communities and an adult day care center. Fifty-seven elderly individuals (mean age 79.49 +/- 7.26 yrs; mean education 11.33 +/- 3.8 yrs; 72% women). After completing a comprehensive medical history, and with drug vials and pillboxes available for consultation, each subject described how he or she was taking prescribed oral drugs. The MedTake test evaluated dosage, indication, food or water coingestion, and regimen. For each agent, the test was scored as percentage of correct actions, equally weighted, and compared with label directions or self-expressed physician changes. A composite MedTake test score (0-100%) summarized a subject's overall ability to take their drug(s) safely A follow-up qualitative assessment by a single pharmacist assigned each agent to one of four potential risk categories: correct use, partial correct use without potential clinical significance, partial correct use with potential clinical significance, or incorrect use with high potential of clinical significance. Most subjects (80%) managed their own drug therapy; 70% used reminder systems (calendar, pillbox). The number of medical conditions and prescription drugs was 6.11 +/- 4.2 and 5.88 +/- 3.44, respectively. Of 325 agents, correct dosage was reported for 94% (306), correct indication for 95% (309), correct coingestion with food or water for 97% (314), and correct regimen for 89% (288). The composite MedTake test score was 88.5 +/- 21.3%. The multivariate model, with that score as the dependent variable, adjusted for age and sex, used Mini-Mental State Examination (p = 0.002) and Medicaid assistance within 10 years (p = 0.021) as significant factors. The most frequent problem was underdosing of cardiovascular drugs. Seniors' ability to take oral prescription drugs safely was affected by cognitive function and socioeconomic status. Although the MedTake test helped identify some problems with therapy adherence, a pharmacist's follow-up evaluation of comprehensive medical and drug histories identified additional potentially clinically significant problems in 20% of subjects.",2003.0,0,0
185,12394674,Current and future pharmacological treatment for overactive bladder.,Naoki Yoshimura; Michael B Chancellor,"Urinary incontinence and overactive bladder are important and common conditions that have received little general medical attention. We reviewed the magnitude and impact of these conditions, and discuss pharmacotherapy as well as new drugs under investigation. The main emphasis of this review is pharmacological therapy for the bladder. We discuss currently available agents, drugs under development and pharmacological targets that would be suitable targets for treating overactive bladder. Drugs such as duloxetine that target not bladder smooth muscle, but rather central nervous system control of the micturition reflex are undergoing clinical trials. We also discuss intravesical therapy and alternative drug delivery methods, such as intravesical capsaicin and botulinum toxin, with special emphasis on approaches to modulate bladder afferent nerve function for preventing overactive bladder. There are many advantages to advanced drug delivery systems, including long-term therapeutic efficacy, decreased side effects and improved patient compliance. Future speculation such as gene therapy holds great promise for overactive bladder because it is possible to access all genitourinary organs via endoscopy and other minimally invasive techniques that are ideally suited for gene therapy. Traditional anticholinergic therapies are limited in their effectiveness. There is great hope for future research regarding voiding dysfunction and urinary incontinence through a focus on afferent nerve intervention for preventing overactive bladder.",2002.0,0,0
186,12394756,Giggle incontinence in children: a manifestation of detrusor instability.,Manju Chandra; Reeta Saharia; Qiuhu Shi; Vanessa Hill,"To our knowledge the prevalence and cause of giggle incontinence in children is not known. We hypothesized that laughter may induce unstable detrusor contractions in children susceptible to detrusor instability. We evaluated the prevalence of diurnal voiding symptoms of urinary urgency, urge incontinence, pelvic withholding maneuvers and hesitancy in patients with giggle incontinence, the prevalence of giggle incontinence in patients with diurnal voiding symptoms, the prevalence of the 2 conditions in first degree relatives of patients with giggle incontinence, the influence of treatment for detrusor instability on the frequency of giggle incontinence and the prevalence of diurnal voiding symptoms in control children with giggle incontinence. Of 1,421 children 5 to 15 years old referred to the pediatric nephrology department for various problems 109 were diagnosed with giggle incontinence and 460 had diurnal voiding symptoms. A total of 627 children visiting the pediatrician office whose parents completed a survey questionnaire served as controls. Diurnal voiding symptoms were noted in 95% of the patients with giggle incontinence, while giggle incontinence was noted in 23% of those with diurnal voiding symptoms. Of the patients with giggle incontinence a positive family history for that entity and diurnal voiding symptoms was noted in 13% and 28%, respectively. Giggle incontinence improved in all patients after treatment for detrusor instability and it resolved completely in 89%. Giggle incontinence recurred with a relapse of diurnal voiding symptoms in 28 cases and improved with improved diurnal voiding symptoms during modification of therapy. Diurnal voiding symptoms were present in 43% of the 157 controls with giggle incontinence. Giggle incontinence results from detrusor instability induced by laughter and it improves with effective treatment of detrusor instability.",2002.0,0,0
187,12409875,Conservative management in neurogenic bladder dysfunction.,Ahmet R Aslan; Barry A Kogan,"A few decades ago, urinary diversion, usually with an ileal conduit, was the ultimate outcome for most children with spina bifida. The revolutionary institution of clean intermittent catheterization has changed the algorithm totally. Furthermore many new drugs have been developed during the past decade and have decreased the need for surgery dramatically. In this article, we will focus on the most recent data on new modalities of therapy to help avoid urinary diversion or bladder augmentation. In addition to clean intermittent catheterization and oxybutynin treatment, a new generation of anticholinergic medications, such as tolterodine, has been developed. For patients who drop out because of the side-effects of oral administration, new methods of administration are now available, including extended release and intravesical instillation. For those unresponsive, botulinum-A toxin and resiniferatoxin are two relatively new drugs in the field, administered as intravesical injection and instillation, respectively. Intravesical or transdermal electrical stimulation, sacral nerve stimulation and biofeedback therapy are under development, but as currently administered, are not yet completely successful. Although life-saving in many respects, bladder augmentation introduces life-long risks of its own. Our goal in describing 'conservative' management is to prevent this step. Many alternatives to surgery are available now and more effective strategies are under development.",2003.0,0,0
188,12423868,Drug therapy of urinary urge incontinence: a systematic review.,Guenther Haeusler; Harald Leitich; Mick van Trotsenburg; Alexandra Kaider; Clemens B Tempfer,"To review the efficacy of drug therapy for urinary urge incontinence by examining the published literature. In October 1999, we searched the medical databases MEDLINE, EMBASE, and Cochrane Controlled Trials Register to identify prospective randomized, double-blind, placebo-controlled clinical trials in the English literature evaluating drug therapy (except hormonal therapy) of urinary urge incontinence. Trials were categorized by type of drug and outcome variables. Forty-seven trials were identified. Twenty-four, 12, and 11 trials evaluated anticholinergic drugs, drugs with anticholinergic and calcium antagonistic properties, and alternative regimens, respectively. Data regarding treatment effects of anticholinergic drugs are consistent with a high therapeutic efficacy and characteristic side effects. Therapeutic efficacy and side effect patterns of terodiline, an agent with anticholinergic and calcium antagonistic properties, were comparable to those of anticholinergic agents. Terodiline, however, has been withdrawn from the market because of its association with cardiac arrhythmia. Of the investigated alternative drug regimens, the papaverine-like smooth muscle relaxant flavoxate was reported to be ineffective. Studies investigating the dopamine agonist bromocryptine, the alpha-adrenoceptor blocker prazosin, or the gamma-aminobutyric acid receptor agonist baclofen showed subjective and/or objective improvement of symptoms without reaching statistical significance, whereas the tricyclic antidepressant doxepin, the neurotoxin capsaicin, and the prostaglandin synthase inhibitor flurbiprofen led to statistically significant subjective and/or objective improvement of symptoms. No data for subjective and/or objective improvement of symptoms could be extracted from the studies using the anticholinergic and calcium antagonistic agent propiverine and the calcium antagonist thiphenamil. Published trials support anticholinergic drugs as efficacious therapy for urinary urge incontinence, with predictable side effects. At present, these agents represent the pharmacological treatment of choice for this condition. The potential value of selected alternative drugs is underscored by the available data.",2002.0,0,1
189,12425862,Methodologic shortcomings inherent in a post-hoc analysis.,David R Staskin,,2003.0,0,0
190,12425864,Advances in drug delivery: improved bioavailability and drug effect.,Roger R Dmochowski; David R Staskin,"Alterations in drug delivery produce substantial changes in the bioavailability of anticholinergic agents. These bioavailability differences change the efficacy and tolerability of this drug class, which consistently enhances patient compliance and overall drug effect. In order for drug delivery to alter successfully the bioavailability of a specific agent, the metabolism of that agent and the effect of the degradatory pathway on drug-parent compound levels need to be established. This will enable researchers to design improved or altered delivery pathways to maximize the benefits of these agents. Intestinal metabolism is known to affect certain agents, specifically oxybutynin chloride. Therefore, delivery techniques have been designed that either substantially lower or totally bypass intestinal (presystemic) metabolism. These alternate paths include extended-release oral, cutaneous, intravesical, and intravaginal routes. In addition, improvements in drug delivery have also been found to influence positively efficacy and tolerability profiles associated with tolterodine tartrate, another anticholinergic agent. A long-acting oral formulation has been shown to increase drug efficacy while decreasing tolerability concerns and side effects such as xerostomia. These salubrious effects are, in part, due to the more stable serum-drug concentrations that are imparted by this long-acting formulation.",2003.0,0,0
191,12465081,Presumed rapid eye movement behavior disorder in Machado-Joseph disease (spinocerebellar ataxia type 3).,Joseph H Friedman,"Rapid eye movement behavior disorder (RBD) is a recently recognized sleep disorder in which patients are occasionally not paralyzed during the dream portions of sleep. When not idiopathic, this state has been associated primarily with parkinsonian conditions but also with a small number of medications and other neurodegenerative disorders. Dopamine deficiency may play a role in some patients. This report describes the occurrence of a syndrome that appears to be RBD in 6 of 7 patients followed with Spinocerebellar ataxia type 3 (Machado-Joseph disease). Polysomnography was normal in 1 patient. Two of these patients had had single photon emission computed tomographic imaging of the dopamine transporter 1 year previously.",2003.0,0,0
192,12469258,Treatment of neuropathic urinary and faecal incontinence.,L Skobejko-Włodarska,"The author presents 14 children after meningomyelocoele repair with faecal and urinary incontinence, aged from 6 to 17 years who have undergone the MACE procedure. MACE with synchronous Mitrofanoff continent stoma creation was performed in one child with severe stenosis of the urethra. MACE with simultaneous bladder augmentation was used in 10 patients. 5 of them underwent colocystoplasty, 3 had ileocystoplasty and 2 ureterocystoplasty. Of these 10 children, three have additionally undergone the Mitrofanoff procedure. Patients' follow-up ranged from six months to two years. Three children had trouble with the MACE stoma because of its stenosis. One of them required revision of the stoma. All patients became clean and dry, and this operation improved not only their quality of life, but also their independence.",2003.0,0,0
193,12469985,Female stress and urge incontinence in family practice: insight into the lower urinary tract.,L Viktrup,"As many as 25% of all women are affected by urinary incontinence, but only a few are treated. This frequent, often medically unrecognised, condition occurs in women of all ages. The continence mechanism is based on bladder detrusor control, intact anatomical structures in and around the urethra, correct positioning of the bladder neck and a comprehensive innervation of the lower urinary tract. Age and childbearing are established risk factors for the development of urinary incontinence, but other factors are currently suggested. The evaluation of urinary incontinence should include history, gynaecological examination, urine test, frequency-volume diary and a pad-weighing test. Female urinary incontinence can be treated in general practice by simple means, e.g. pelvic floor muscle training, bladder training, electrostimulation, drug therapy, or a combination of these approaches. This review updates the knowledge of the continence mechanism and summarises the epidemiology, risk factors, assessment and treatment of urinary incontinence in general practice.",2003.0,0,0
194,12475676,Value of increase in bladder capacity in treatment of refractory monosymptomatic nocturnal enuresis in children.,S De Wachter; A Vermandel; K De Moerloose; J J Wyndaele,"To evaluate children with refractory monosymptomatic nocturnal enuresis to determine whether detrusor overactivity (DOA) plays a role in 4 weeks of unsuccessful treatment with retention control training (RCT); whether an increase in bladder capacity can eventually be obtained by RCT plus oxybutynin; and whether the increase in capacity is the primary key to success. Sixty-eight children with refractory monosymptomatic nocturnal enuresis were included. They all had a maximal cystometric capacity less than the age-expected value. RCT was done by water loading and retention to the point of urgency once daily. During training, changes in bladder capacity were evaluated by voiding charts. If after 4 weeks of RCT, less than a 10% increase in bladder capacity was noted, oral oxybutynin was added. The incidence of DOA was 66%. After 4 weeks of RCT, the bladder capacity increased in 20.6%. Combining RCT with oxybutynin led in the end to normalization of the bladder capacity in 79.4%. Older age and high-pressure DOA negatively influenced the ability to increase the bladder capacity. Fifteen children became completely dry, mainly by converting enuresis to nocturia. Unsuccessful RCT is often caused by DOA, especially if a bladder capacity rise of at least 10% cannot be achieved within 4 weeks. If oxybutynin is added to the treatment, normalization of bladder capacity can be obtained in most. This increased bladder capacity cures enuresis only in a minority by sharpening their arousal and provoking nocturia.",2003.0,0,0
195,12476518,Pharmacologic management of urinary incontinence in women.,Alan J Wein; Eric S Rovner,"This article summarizes current thought regarding the efficacy of various types of drug therapy for incontinence in women, borrowing liberally from similar previous presentations. Space limitations for this chapter necessitate some simplification and condensation of these subjects. References have generally been chosen because of their informational or review content and not because of originality or initial publication on a particular subject.",2003.0,0,0
196,12476529,Urinary incontinence in girls.,Jennifer M Abidari; Linda M D Shortliffe,"Girls with incontinence may have minor irritative conditions or undiagnosed anatomic abnormalities that may require surgery. These abnormalities can be identified during a comprehensive history and physical examination that focuses on voiding signs and symptoms. Urinary tract infection and constipation if present should be identified. Most girls with daytime wetting will respond to conservative therapy using timed voiding, dietary changes, and anticholinergic medication. Uroflowmetry with a postvoid residual urine measurement can identify girls who may benefit from biofeedback to treat pelvic floor dysfunction. Formal urodynamics and spinal magnetic resonance imaging should be done in girls refractory to treatment. Instruments and tools to quantify dysfunctional voiding symptoms are being developed. Because most dysfunctional voiding will be treated clinically, these validated tools will be useful in documenting severity of symptoms and clinical outcomes.",2003.0,0,0
197,12477661,,,,,0,0
198,12478180,"Therapeutic efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with diurnal urinary incontinence.",Y Reinberg; J Crocker; J Wolpert; D Vandersteen,"We compare the tolerability and efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with nonneurogenic diurnal urinary incontinence and symptoms of overactive bladder. Children with a history of diurnal urinary incontinence were arbitrarily assigned to extended release oxybutynin, immediate release tolterodine or long acting tolterodine. The dose was titrated until effective (onset of complete diurnal urinary continence), maximal recommended dosage was achieved or bothersome anticholinergic side effects developed. An independent observer recorded the dose used, anticholinergic side effects and efficacy of therapy (incidence of urinary frequency, urgency, posturing and urinary incontinence). The study included 86 girls and 46 boys. There were no statistically significant differences among the 3 treatment groups regarding the presence of peripheral or central nervous system anticholinergic side effects. Extended release oxybutynin and long acting tolterodine were significantly more effective at reducing daytime urinary incontinence than immediate release tolterodine (p <0.01 and 0 <0.05, respectively). Extended release oxybutynin was significantly more effective then long acting tolterodine for complete resolution of diurnal incontinence (p <0.05). Extended release oxybutynin and long acting tolterodine are more effective than immediate release tolterodine in decreasing diurnal urinary incontinence. Extended release oxybutynin chloride is more effective than either immediate or long acting tolterodine for control of daytime urinary incontinence and urinary frequency.",2003.0,0,0
199,12483499,Significance of low compliance bladder in cauda equina injury.,J C Shin; C-i Park; H J Kim; I Y Lee,"Prospective investigation using serial urodynamic studies. To evaluate type of neurogenic bladder and to observe changes of autonomous detrusor contraction (ADC) after the normalization of the compliance and capacity of the bladder in cauda equina injury. Spinal Cord Injury Unit, Yonsei Rehabilitation Hospital, Seoul, Korea. Urodynamic studies were performed in 50 patients with complete cauda equina injury from trauma with an infusion ratio of 30 ml/min. Findings of urodynamic studies and clinical features of patients with low compliance were compared with those of the normal compliant patients. Fourteen patients with low compliance received oral administration of oxybutynin and propiverine and intravesical instillation of oxybutynin to increase the compliance and capacity of the bladder, and follow-up urodynamic studies to monitor the change were undertaken. Bladder compliance was decreased in 14 (28%) patients and normal in 36 (72%) patients. There was a significantly long time interval between the onset of injury and the initiation of rehabilitative treatment in the neurogenic bladder group with low compliance when compared to those of the normal compliance group (P < 0.05). Clean intermittent catheterization was used as the voiding method, significantly less than the normal compliance group (P < 0.05). ADC was observed in six out of fourteen patients with low compliance neurogenic bladder, but none in the normal compliance group. Upon the completion of conservative treatment, ADC disappeared in four patients whose compliance and capacity of the bladder were normalized on follow-up urodynamic studies. ADC was only observed in the low compliant bladder and as ADC disappeared when compliance and capacity of the bladder was normalized; low compliance appeared to be the main cause of ADC. In addition, this study supports that the maintenance of compliance of the bladder may be the most important factor in the management of neurogenic bladder.",2003.0,0,0
200,12493364,Muscarinic receptor subtypes and management of the overactive bladder.,Christopher R Chapple; Tomonori Yamanishi; Russell Chess-Williams,"Anticholinergic agents are the most widely used therapy for urge incontinence despite exerting adverse effects, such as constipation, tachycardia, and dry mouth, that limit their use. These adverse effects result from a lack of selectivity for the bladder over other organs. Although M2-muscarinic receptors are the predominant cholinoreceptor present in urinary bladder, the smaller population of M3-receptors appears to be the most functionally important and mediates direct contraction of the detrusor muscle. M2-receptors modulate detrusor contraction by several mechanisms and may contribute more to contraction of the bladder in pathologic states, such as bladder denervation or spinal cord injury. Prejunctional inhibitory M2-receptors or M4-receptors and prejunctional facilitatory M1-muscarinic receptors in the bladder have also been reported, but their relevance to the clinical effectiveness of muscarinic antagonists is unknown. In clinical studies, tolterodine, a nonselective muscarinic antagonist, has been reported to be equally effective to oxybutynin but to induce less dry mouth. Controlled-release and intravesical, intravaginal, and rectal administrations of oxybutynin have all been reported to cause fewer adverse effects. Conversely, darifenacin, a new M3-selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. Whether M3-selective or nonselective muscarinic antagonists will be the most clinically effective for the overactive bladder-preserving the best balance between efficacy and tolerability-has yet to be established, and comparative clinical trials between compounds, such as darifenacin (M3 selective) and tolterodine (nonselective) will be required.",2003.0,0,0
201,12507545,Are urodynamic tests useful tools for the initial conservative management of non-neurogenic urinary incontinence? A review of the literature.,Enrico Colli; Walter Artibani; John Goka; Fabio Parazzini; Alan J Wein,"To summarise the evidence for the role of urodynamic tests in the diagnosis and classification of urinary incontinence. Reference lists in relevant papers were reviewed and MEDLINE searches conducted. The mean sensitivity (specificity) of clinical history versus urodynamic tests was 0.82 (0.57) for stress incontinence, 0.69 (0.60) for urge incontinence/overactive bladder, and 0.51 (0.66) for patients with mixed incontinence. The proportion of women with a clinical diagnosis of urinary incontinence but with normal findings from urodynamic tests ranged from 3 to 8%. Overall sensitivity of urodynamic tests was about 85-90% in the diagnosis of urodynamic stress incontinence, but generally lower following diagnosis of urge and mixed incontinence. No relationship emerged between urodynamic test results and response to medical treatment. This literature review shows that the sensitivity of clinical history versus urodynamic tests was 0.82, 0.69 and 0.51 respectively for stress, urge and mixed urinary incontinence. It also suggests that urodynamic diagnosis does not predict response to treatment. These data add to the ongoing 'urodynamics or no urodynamics' debate in the evaluation of urinary incontinence and show that urodynamic testing may not be helpful for patients receiving initial non-invasive therapy. These data are in line with the conclusions of the 1st and 2nd International Consultations on incontinence.",2003.0,0,0
202,12509373,Influences on GPs' decision to prescribe new drugs-the importance of who says what.,Helen Prosser; Solomon Almond; Tom Walley,"The aim of this study was to understand the range of factors that influence GPs' uptake of new drugs A total of 107 GPs selected purposively from high, medium and low new drug prescribing practices in two health authorities in the north west of England were interviewed using the critical incident technique with semi-structured interviews. Interview topics included reasons for prescribing new drugs launched between January 1998 and May 1999; reasons for prescribing the new drug rather than alternatives; and sources of information used for each prescribed drug. Important biomedical influences were the failure of current therapy and adverse effect profile. More influential than these, however, was the pharmaceutical representative. Hospital consultants and observation of hospital prescribing was cited next most frequently. Patient request for a drug, and patient convenience and acceptability were also likely to influence new drug uptake. Written information was of limited importance except for local guidelines. GPs were largely reactive and opportunistic recipients of new drug information, rarely reporting an active information search. The decision to initiate a new drug is heavily influenced by 'who says what', in particular the pharmaceutical industry, hospital consultants and patients. The decision to 'adopt' a new drug is clinched by subsequent personal clinical experience. Prescribing of new drugs is not simply related to biomedical evaluation and critical appraisal but, more importantly, to the mode of exposure to pharmacological information and social influences on decision making. Viewed within this broad context, prescribing variation becomes more understandable. Findings have implications for the implementation of evidence-based medicine, which requires a multifaceted approach.",2003.0,0,0
203,12516010,,,,,0,0
204,12540342,Urinary incontinence in nursing homes for older people.,Joanna Durrant; Jeremy Snape,At least 50% of nursing home residents in Britain and North America suffer from urinary incontinence. It is associated with resident and staff morbidity. The assessment and management of such residents will depend on the capacity of the care staff and the capability of the resident. The minimum data set and resident assessment protocol may have a role in the assessment of incontinent residents. Behavioural strategies are more likely to be beneficial than drug treatment.,2003.0,0,0
205,12555610,"[""New wonder pill!""--what do Norwegian newspapers write].",Sigurd Høye; Per Hjortdahl,"The news media are an important source of information on new medical treatments. There is, however growing concern that some of the coverage may be inaccurate and overly enthusiastic, thereby misleading the general population. Eight major Norwegian newspapers were screened for articles on the benefits and risks of all the 60 new medications introduced on the Norwegian market from July 1998 through March 2000. We found a total of 492 articles describing 18 new medications over the period January 1998 through June 2000. Of the 357 stories that mentioned benefits, 79% did not report this in any greater detail, 51% gave the medication a positive coverage, while 19% used overly enthusiastic terms like ""wonder pill"". 39% of the 492 stories pointed to potentially harmful effects of the medication while 27% mentioned costs. 174 stories cited at least one expert describing the effects of the medication, but only four of these stories disclosed financial ties between the expert and the manufacturer of the specific drug. Press releases from drug companies were cited twice as often as papers in medical journals. The Norwegian news media usually given new medications an overly enthusiastic coverage, while there is incomplete information about the benefits, risks and costs of the drugs as well as about the financial ties between medical experts and the pharmaceutical industry.",2003.0,0,0
206,12572529,Effect of tolterodine on the anticoagulant actions and pharmacokinetics of single-dose warfarin in healthy volunteers.,Mohamad Rahimy; Bengt Hallén; Prem Narang,"This randomized, double-blind, crossover study investigated the potential effects of tolterodine ((R)-N,N-diisopropyl-3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropanamine, CAS 124937-51-5), an antimuscarinic agent for the treatment of the overactive bladder, on the anticoagulant actions and pharmacokinetics of single-dose warfarin (CAS 81-81-2) in 20 healthy male volunteers. In terms of study design, volunteers randomly received oral tolterodine L-tartrate (2 mg twice daily) or matching placebo for 7 days, with a single oral dose of warfarin (25 mg) administered on day 4 of each treatment period. R-(+)- and S-(-)-warfarin pharmacokinetics were estimated from plasma levels measured up to 96 h post-dose, in conjunction with assessment of prothrombin time and factor VII activity. Pharmacokinetics of tolterodine and its active 5-hydroxymethyl metabolite ((R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethyl-phenyl)-3-phenylpropanamine; 5-HM), in the presence and absence of warfarin, were also determined. Relative to placebo, tolterodine had no discernible effect on the anticoagulant actions of warfarin. Point estimates of the tolterodine: placebo ratios for prothrombin time and factor VII activity were 1.00 (90% confidence interval [CI]: 0.91-1.10) and 0.91 (90% CI: 0.83-0.99), respectively, consistent with equivalence. No clinically significant changes in the pharmacokinetics of R-(+)- and S-(-)-warfarin were noted. Serum concentration-time profiles and the pharmacokinetics of tolterodine and 5-HM were similar in the presence and absence of warfarin. There were no safety concerns. These findings indicate that co-administration of tolterodine and warfarin is safe and well tolerated, with no clinically significant pharmacodynamic or kinetic interaction in healthy volunteers.",2003.0,0,0
207,12576796,The natural history of the overactive bladder and detrusor overactivity. A review of the evidence regarding the long-term outcome of the overactive bladder.,Stephen Garnett; Paul Abrams,"The overactive bladder is a widespread medical condition with significant impact on quality of life. We review the existing evidence about the prevalence, impact and long-term followup of the overactive bladder. We also summarize the new International Continence Society terminology associated with the overactive bladder. A MEDLINE search of all available literature regarding the epidemiology and long-term followup or outcome of the overactive bladder was performed. All articles and relevant resources cited in those articles were reviewed. The new International Continence Society terminology and definitions will allow greater consistency in future research. Two large, recently published surveys of the prevalence of overactive bladder give new insight into the widespread nature of the problem and its significant impact on quality of life. There is little good quality evidence currently available on the long-term outcome of overactive bladder. There is little published evidence regarding the natural history of overactive bladder. While recent studies have improved understanding the prevalence of the condition, we still know little about long-term outcome. The few published studies suggest that it is a chronic condition that persists urodynamically and symptomatically.",2003.0,0,1
208,12576837,Which stop test is best? Measuring detrusor contractility in older females.,Thai Lian Tan; Margaret A Bergmann; Derek Griffiths; Neil M Resnick,"Impaired detrusor contractility has an important role in geriatric voiding dysfunction but there are many competing methods of measurement. We compared the performance of 3 methods of measuring detrusor contraction strength to identify the best one. We retrospectively analyzed urodynamics data on 84 females 53 years old or older. All had urge incontinence and were enrolled in a placebo controlled oxybutynin trial. Stop tests (voluntary interruption, mechanical interruption and continuous mechanical occlusion of flow) were performed on each subject. At baseline the voluntary stop test measured lower mean isovolumetric detrusor pressure +/- SD than the mechanical and continuous methods (31.2 +/- 16.0 versus 47.2 +/- 26.5 and 48.7 +/- 24.4 cm. water, respectively). The latter 2 values also correlated highly (r = 0.87). Followup data on 76 women confirmed these results. Based on baseline and followup values in the 20 women who received placebo the continuous occlusion test showed highest test-retest reliability (r = 0.9, p <0.01), followed by the mechanical (r = 0.69, p = 0.01) and voluntary (r = 0.67, p <0.01) stop tests. Treatment with oxybutynin decreased isovolumetric detrusor pressure in all 3 stop tests by up to 6 cm. water. However, the decrease was statistically significant only for the continuous occlusion test. To assess detrusor contraction strength in elderly females with urge incontinence the mechanical stop and continuous occlusion tests are acceptable but the continuous occlusion test has better reliability and better detects slight drug induced changes. Voluntary stop tests greatly underestimate detrusor isovolumetric pressure and should no longer be used.",2003.0,0,0
209,12580556,Neurological disorders cerebrovascular disease and parkinsonism.,Mike B Siroky,"To store and expel urine at appropriate intervals, the lower urinary tract requires extensive input and control from the peripheral autonomic, somatic, and central nervous systems. Neurological disorders, such as cerebrovascular disease and Parkinson's disease, often cause functional disturbances of the lower urinary tract.",2003.0,0,0
210,12601517,A new once-daily formulation of tolterodine provides superior efficacy and is well tolerated in women with overactive bladder.,S Swift; A Garely; T Dimpfl; C Payne; Tolterodine Study Group,"This study evaluated the efficacy and tolerability of new extended-release (ER) tolterodine for the treatment of overactive bladder in women. In this subpopulation analysis of a double-blind multicenter trial, 1235 female patients were randomized to oral therapy with tolterodine ER 4 mg once daily (n=417), tolterodine IR 2 mg twice daily (n=408) or placebo (n=410) for 12 weeks. Both formulations reduced the mean number of urge incontinence episodes per week (both P=0.001 vs placebo); tolterodine ER was more effective than tolterodine IR (P=0.036). Both formulations significantly improved all other micturition chart variables compared to placebo. Dry mouth was the most common adverse event. There were no safety concerns. Toltrodine ER 4 mg once daily is effective and well tolerated in the treatment of women with overactive bladder, and reduces urge incontinence episodes more than the existing IR twice-daily formulation.",2003.0,0,0
211,12603422,The use of tolterodine in children after oxybutynin failure.,S Bolduc; J Upadhyay; J Payton; D J Bägli; G A McLorie; A E Khoury; W Farhat,"To assess the safety and efficacy of tolterodine tartrate prescribed to children who previously failed to tolerate oxybutynin chloride. We reviewed 34 children, followed for>1 year, who were prospectively crossed-over from oxybutynin to tolterodine because of side-effects. The initial diagnosis was dysfunctional voiding in 31 patients. All patients were placed on a behavioural modification protocol. When their symptoms did not improve after 6 months, treatment with an anticholinergic agent was considered. Urodynamic studies were conducted in 20 patients, confirming uninhibited contractions in 19. The remaining 14 patients were empirically started on antimuscarinic or anticholinergic agents. The 34 patients were treated with oxybutynin for a median (range) of 6 (2-84) months. When significant side-effects were reported, they were crossed over to tolterodine. The efficacy of tolterodine was assessed as defined by the International Children's Continence Society, with tolerability assessed and side-effects documented using a questionnaire. The mean age at the first dose of tolterodine was 8.9 years; the dose was 1 mg twice daily for 12 patients and 2 mg twice daily for 22. The median treatment with tolterodine was 11.5 months, with 20 (59%) patients reporting no side-effects; six described the same but tolerable side-effects as with oxybutynin. Eight patients discontinued tolterodine because of side-effects after a median (range) of 5 (1-11) months. The efficacy of tolterodine was comparable with that of oxybutynin, as reported by the questionnaire and voiding diaries. The reduction in wetting episodes at 1 year was> 90% in 23 (68%), more than half in five and less than half (or failure) in six patients. Tolterodine is tolerated well in children. In this subgroup of patients who could not tolerate oxybutynin, 77% were able to continue tolterodine treatment with no significant side-effects.",2003.0,0,0
212,12603423,Posterior urethral injuries and the Mitrofanoff principle in children.,L G Freitas Filho; J Carnevale; A R Melo Filho; N C Vicente; A C Heinisch; J L Martins,"To report our experience of children with trauma causing posterior urethral injury who at some stage underwent a Mitrofanoff intervention, as post-traumatic urethral injuries can demand long-term treatment which (regardless of the surgical intervention) requires a period of dilatation of the reconstructed urethra. From 1992 to 2001, 14 patients with urethral injuries underwent a Mitrofanoff procedure. Thirteen had been run over by a motor vehicle and had severe hip injuries, and one had a direct non-penetrating perineal impact lesion (13 boys and one girl, aged 2-13 years at the time of the accident). In all cases the Mitrofanoff procedure involved interposing the appendix between the bladder and the umbilicus. Only one of the children (because of extremely high bladder filling pressures) also underwent an augmentation cystoplasty and closure of the bladder neck because there were bony fragments in the urethra. The Mitrofanoff technique was considered useful in most cases. All patients during a given period used the Mitrofanoff conduit to empty their bladder every 3 h; 10 of the 14 are currently voiding urethrally, with an adequate flow, and four are not, but emptying the bladder periodically via the appendicovesicostomy. The only girl in the group has a major hip deformity and is unlikely to undergo urethroplasty; two patients are expecting definitive treatment and the other, although having a patent urethra, has no urinary flow. He is currently 19 years old and has no erections. The treatment of posterior urethral injuries represents a challenge to surgical teams. Although primary suturing of the separated urethral ends is accepted as the best treatment, the construction of a temporary continent urinary diversion may be considered in the most severe cases.",2003.0,0,0
213,12608543,Pharmacokinetics and metabolism of transdermal oxybutynin: in vitro and in vivo performance of a novel delivery system.,R Howard Zobrist; Danyi Quan; Heather M Thomas; Stephanie Stanworth; Steven W Sanders,"The purpose of this work was to characterize in vitro/in vivo delivery and pharmacokinetics of oxybutynin (OXY) and its active metabolite. N-desethyloxybutynin (DEO), by a novel matrix transdermal system (TDS). Two in vivo, randomized, three-way crossover trials examined single/multiple OXY TDS doses. Abdomen, buttock, and hip application sites were compared and dose proportionality was evaluated. Model independent pharmacokinetics, elimination rate constants, and metabolite/drug ratios were derived from both plasma OXY and DEO concentrations. Single/multiple applications of the OXY TDS to the abdomen yielded mean Cmax OXY concentrations of 3.4 +/- 1.1/6.6 +/- 2.4 ng/mL and median tmax of 36/10 h, with steady state achieved during the second application. Plasma OXY and DEO concentrations decreased gradually after Cmax until system removal. Buttock and hip applications resulted in bioequivalent OXY absorption. AUC ratios of DEO/OXY were 1.5 +/- 0.4 (single dose) and 1.3 +/- 0.3 (multiple dose). Mean in vitro OXY skin absorption (186 microg/h) was comparable to the estimated in vivo delivery (163 microg/h) over 96 h. Sustained delivery over 4 days and multiple sites allow a convenient, well-tolerated, twice-weekly OXY TDS dosing. A low incidence of anticholinergic side effects is expected during clinical use because of the avoidance of presystemic metabolism and low DEO plasma concentrations. The consistent delivery, absorption, and pharmacokinetics should result in an effective treatment of patients with overactive bladder.",2003.0,0,0
214,12614251,Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.,A Mattiasson; J Blaakaer; K Høye; A J Wein; Tolterodine Scandinavian Study Group,"To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder. In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined. In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth. Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.",2003.0,0,0
215,12651768,Bladder dysfunction in Duchenne muscular dystrophy.,M MacLeod; R Kelly; S A Robb; M Borzyskowski,"Although bladder function is thought to be unaffected in Duchenne muscular dystrophy, 46/88 boys interviewed had urinary problems. Nine underwent video urodynamics, showing in eight a small capacity, hyperreflexic bladder, and in the ninth (post spinal surgery) hyperreflexia and detrusor sphincter dyssynergia. Urinary dysfunction is a treatable feature of DMD.",2003.0,0,0
216,12669676,Clinical advances in incontinence management. A sampling of products now available to manage urinary incontinence.,,,2003.0,0,0
217,12686854,Successful hypospadias repair with ventral based vascular dartos pedicle for urethral coverage.,Peter D Furness; Joel Hutcheson,"We describe an easy technique to reliably harvest a vascularized dartos pedicle for urethral coverage at the time of urethroplasty in hypospadias surgery. The complication of urethrocutaneous fistula in hypospadias surgery as a result of using this technique is also evaluated. A retrospective review (July 1999 to September 2002) identified 180 pediatric patients who had undergone primary hypospadias surgery by a single surgeon. A modified technique of harvesting a vascularized dartos pedicle was incorporated in 111 hypospadias repairs. A ventral based vascularized dartos pedicle of tissue was used to cover a modified urethroplasty as described by Snodgrass. The intraoperative meatal position before urethroplasty was subcoronal in 95 cases, penile/midshaft in 11 and penoscrotal in 5. The majority of patients (90 of 111) were younger than 12 months at surgery. Ages ranged from 5 months to 16 years (mean 21.1 months). Of the 111 patients reconstruction using the ventral based vascularized dartos pedicle to cover the urethroplasty was successful in 109 (98.2%), and at followup they have an acceptable cosmetic result with no evidence of urethrocutaneous fistula. In 1 patient with distal hypospadias a urethrocutaneous fistula developed, which was recognized 20 months postoperatively. Another patient with penoscrotal hypospadias had a proximal fistula at 6 months. There were no recognized intraoperative urethral injuries or complications. Followup ranged from 3 to 38 months (mean 19.1). The ventral based vascularized dartos pedicle urethral coverage procedure is an easy and reliable technique to harvest adequate vascularized tissue to cover a hypospadias urethroplasty. In this small single surgeon series, this technique appears to have contributed to a low rate of urethrocutaneous fistulas after hypospadias repair.",2003.0,0,0
218,12699495,An unusual cause of 'incontinence' after hysterectomy.,D Robinson; M Savvas; L Cardozo,,2003.0,0,0
219,12702614,Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review.,Peter Herbison; Jean Hay-Smith; Gaye Ellis; Kate Moore,"To determine the effectiveness of anticholinergic drugs for the treatment of overactive bladder syndrome. Systematic review of randomised controlled trials. Published papers and abstracts. Randomised controlled trials with anticholinergic drug treatment in one arm and placebo in another. Primary outcomes of interest were patient perceived cure or improvement in symptoms, differences in number of incontinent episodes and number of voids in 24 hours, and side effects. Secondary outcomes of interest were urodynamic measures of bladder function (volume at first contraction, maximum cystometric capacity, and residual volume) and adverse events. 32 trials were included, totalling 6800 participants. Most trials were described as double blind but were variable in other aspects of quality. At the end of treatment, cure or improvement (relative risk 1.41, 95% confidence interval 1.29 to 1.54), differences in incontinent episodes in 24 hours (estimated mean difference 0.6, 0.4 to 0.8), number of voids in 24 hours (0.6, 0.4 to 0.8), maximum cystometric capacity (54 ml, 43 ml to 66 ml), and volume at first contraction (52 ml, 37 ml to 67 ml), were significantly in favour of anticholinergics (P<0.0001 for all). Anticholinergics were associated with significantly higher residual volumes (4 ml, 1 ml to 7 ml; P=0.02) and an increased rate of dry mouth (relative risk 2.56, 2.24 to 2.92; P<0.0001). Sensitivity analysis, although affected by small numbers of studies, showed little likelihood of an effect of age, sex, diagnosis, or choice of drug. Although statistically significant, the differences between anticholinergic drugs and placebo were small, apart from the increased rate of dry mouth in patients receiving active treatment. For many of the outcomes studied, the observed difference between anticholinergics and placebo may be of questionable clinical significance. None of these studies provided data on long term outcome.",2003.0,0,1
220,12712123,Urethral adenocarcinoma associated with urethral diverticulum in a patient with progressive voiding dysfunction.,Walter S von Pechmann; Marisa A Mastropietro; Timothy J Roth; Douglass S Hale,Urethral adenocarcinoma associated with urethral diverticulum is a rare condition that requires a high index of suspicion to ensure early diagnosis and appropriate therapy. The development of urethral stenosis in a patient with a urethral diverticulum warrants early biopsy to rule out a malignant lesion.,2003.0,0,0
221,12734610,Inappropriate medication use among hospitalized older adults in Italy: results from the Italian Group of Pharmacoepidemiology in the Elderly.,Graziano Onder; Francesco Landi; Matteo Cesari; Giovanni Gambassi; Pierugo Carbonin; Roberto Bernabei; Investigators of the GIFA Study,"To determine the prevalence of inappropriate medication use among hospitalized older adults and to identify predictors of this use. A total of 5734 patients (mean age 79 years) admitted to geriatric and internal medicine wards participating in the study in 1995 and 1997 were included in this analysis. Inappropriate medication use was defined on the basis of the criteria published by Beers in 1997. Only medications used during hospital stay were considered for the present study. During hospital stay, 837 (14.6%) patients received one or more medications classified as inappropriate based on Beers criteria. Ticlopidine ( n=346; 6.0% of the study sample) was the most frequently used medication among those in Beers' list, followed by digoxin ( n=174; 3.0%) and amytriptyline ( n=113; 2.0%). The multivariate analysis showed that age [75-84 years vs 65-74 years, odds ratio (OR) 0.85, 95% confidence interval (CI) 0.71-1.00; >or=85 years vs 65-74 years, OR 0.58, 95% CI 0.46-0.73], cognitive impairment (OR 0.77, 95% CI 0.64-0.94), Charlson co-morbidity index (>or=2 vs 0-1, OR 1.20, 95% CI 1.02-1.40) and overall number of medications used during hospital stay (5-8 medications vs <5 medications, OR 2.20, 95% CI 1.72-2.82; >or=9 medications vs <5 medications, OR 3.68, 95% CI 2.86-4.73) were significantly associated with use of inappropriate medications. Inappropriate medication use was common among hospitalized older adults. The most important determinant of risk of receiving an inappropriate medication was the number of drugs being taken. Older age and cognitive impairment were associated with a reduced likelihood of using an inappropriate medication.",2003.0,0,0
222,12746713,[The medical treatment of overactive bladder].,C Beneton; O De Parisot,"Overactive bladder, very frequent in neurological disorders, leads to very distressing symptoms such as urgency, frequency and incontinence which may dramatically impair the patient's quality of life. The medical approach is essentially pharmacological but the management of the nociceptive factors must not be neglected. In the mild urinary dysfunctions, bladder training can be advised. The pharmacological treatment aims at reducing the parasympathetic activity or at deafferenting the bladder. The antimuscarinic agents are an essential part of the treatment. Oxybutynin is the most widely used medication but recent agents like tolterodin have a better tolerability. Other drugs can also be used such as desmopressin, flavoxate. New molecules are under experiment (darifenacin). In case of troublesome side-effects or resistance to oral medications, local treatments are considered. Intravesical oxybutynin has been tried but has a short-lived efficacy. Intravesical instillation of capsaicine or resiniferatoxin blocks C-fibres afferents and leads to clinical and urodynamic improvement. Recently, injections of botulinum-A toxin in the detrusor have been advocated aiming at blocking the transmission of parasympathetic impulse. The first studies report encouraging results. All these local treatments resulting in bladder paresis are recommended for patients performing self-catheterization. Should these treatments fail, other therapeutic approaches are considered such as intrathecal treatment, neuromodulation, before deciding on neurosurgical or urosurgical procedures.",2003.0,0,1
223,12756144,Tolterodine and memory: dry but forgetful.,Kyle B Womack; Kenneth M Heilman,"Anticholinergic drugs are known to produce or enhance cognitive deficits. Tolterodine tartrate is marketed as a bladder-selective anticholinergic drug that is reported to be free of significant cognitive adverse effects. To describe a 46-year-old woman who had memory loss and abnormal memory test results that improved when she discontinued tolterodine therapy. While taking tolterodine, the patient's score on the delayed free recall portion of the Hopkins Verbal Learning Test-Revised was at the first percentile. One month after discontinuing tolterodine therapy, this test was administered a second time using an alternative form and she showed marked improvement scoring above the 75th percentile. Tolterodine therapy caused cognitive dysfunction in our patient. It is possible that cognitive dysfunction is a common result of tolterodine treatment, but in the absence of testing, remains undiagnosed. Alternatively, our patient may have had aberrant metabolism of this drug or an increased sensitivity as a result of incipient Alzheimer disease.",2003.0,0,0
224,12771763,"Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study.",A Athanasopoulos; K Gyftopoulos; K Giannitsas; J Fisfis; P Perimenis; G Barbalias,"We evaluate the effect of tolterodine combined with tamsulosin on quality of life in patients with bladder outlet obstruction and concomitant detrusor instability. The study included 50 consecutive patients with urodynamically proven mild or moderate bladder outlet obstruction and concomitant detrusor instability. All patients were initially treated with 0.4 mg. tamsulosin orally once a day. A week later the patients were randomly allocated into group 1-25 who continued treatment with tamsulosin only and, group 2-25 who also received 2 mg. tolterodine orally twice daily. Reevaluation with a quality of life questionnaire and urodynamic study was performed after 3 months. Two patients from group 2 stopped tolterodine while 1 patient from each group stopped tamsulosin because of hypotension. Analysis revealed statistically significant improvement in quality of life scores only in group 2 patients (mean score 525.0 and 628.4 before and after treatment, respectively, 2-sided t test p = 0.0003). A significant difference was noted in both groups after treatment for maximum flow rate and volume at first contraction. Additionally, in group 2, a statistically significant difference was observed for maximum detrusor pressure and maximum unstable contraction pressure after treatment. Combination treatment with an alpha-blocker (tamsulosin) plus an anticholinergic (tolterodine) improves quality of life in patients with bladder outlet obstruction and concomitant detrusor instability. Interestingly, no acute urinary retention was observed and tolterodine did not affect the quality of urine flow or residual urine volume. The proposed combination appears to be an effective and relatively safe treatment option in patients with bladder outlet obstruction and detrusor instability.",2003.0,0,0
225,12777612,Index of suspicion.,,,2003.0,0,0
226,12790272,Urinary incontinence. Non-surgical management by family physicians.,K N Moore; B Saltmarche; A Query,"To review current evidence on conservative management of urinary incontinence (UI) by family physicians. Articles were sought through MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CINAHL, PsycLit, ERIC, two consensus meetings, and review of abstracts presented at urology meetings. References of these articles were searched for relevant trials. Strong evidence supports bladder training, pelvic floor exercises, and some medications, but only fair evidence supports fluid adjustment, caffeine reduction, and stopping smoking. Weight loss and exercise are supported by expert opinion only. Consensus opinion is that, whenever possible, conservative management should be considered first. Good evidence shows that initial management by primary care physicians is effective. After basic assessment and tests, strategies such as bladder retraining, pelvic floor exercises, and lifestyle modifications, augmented by appropriate medications, can be successful. If initial strategies are unsuccessful, patients can be referred. More than a million Canadians suffer from UI. In almost all cases, family physicians are the first health professionals contacted by patients. Basic assessment and conservative management can go far to ameliorate the problem.",2003.0,0,0
227,12792375,Polypharmacy and the elderly.,Rakesh B Patel,"Polypharmacy is the concurrent use of several different medications used by the same individual, which in some cases can lead to drug-drug interactions. Elderly patients often are faced with polypharmacy when they have multiple disease processes. Declining organ function, as part of the normal aging process, adds to the problem of adverse drug effects in this population. To minimize polypharmacy, prescribers aim to treat multiple disease conditions with a single agent if possible. Pharmacists can often help in drug selection, if given a set of criteria. This article is intended to help infusion professionals provide safe medication treatment by understanding how aging organ systems and medications affect the elderly.",2003.0,0,0
228,12796688,Treatment of daytime urinary incontinence in children: a systematic review of randomized controlled trials.,Premala Sureshkumar; Wendy Bower; Jonathan C Craig; John F Knight,"We sought to determine the benefits and harms of interventions for children with daytime urinary incontinence. Trials of any interventions for children with primary daytime incontinence (the urge syndrome and/or dysfunctional voiding) were identified from the Cochrane Controlled Trials Register, MEDLINE, EMBASE, reference lists of articles, abstracts from conference proceedings and contact with known experts in the field. Once identified, trial quality was assessed, data were extracted and results were expressed in terms of relative risks (RR) with 95% confidence intervals (CI) for individual trials, and summary estimates were obtained using a random effects model. All steps were done by 2 independent reviewers. Randomized trials of terodiline (2 studies), daytime alarms (1), imipramine (1) and biofeedback/oxybutynin (1) involving 383 children were reviewed. No intervention was demonstrated to be effective. In the latter trial, which was the only one to evaluate a currently used intervention, after 9 months of treatment there was no difference in the proportions of children with unimproved daytime wetting with oxybutynin (RR 0.74, CI 0.26 to 2.13) and biofeedback (0.92, 0.59 to 1.43) compared with placebo. No intervention tested in a trial to date has been proved to be of benefit to children with daytime urinary incontinence.",2003.0,0,0
229,12797715,Multinational study of reliability and validity of the King's Health Questionnaire in patients with overactive bladder.,Pat Ray Reese; Andreas M Pleil; Gary J Okano; Con J Kelleher,"Overactive bladder (OAB) has substantial impact on health-related quality of life (HRQoL). The purpose of this research was to evaluate the psychometric properties of the King's Health Questionnaire (KHQ). The KHQ (n = 1284) was administered at baseline and 12 weeks post-treatment in a multinational, double-blind, randomized clinical trial of tolterodine for treatment of OAB. Country-specific psychometric analyses of HRQoL instruments were performed. Countries demonstrating marginal psychometric properties on the KHQ were pooled with same-language countries, re-evaluated, and aggregate analysis performed on the pooled data. Internal consistency of the KHQ was high, item characteristics were good, most assumptions of summed scales were met, and it is externally valid and consistent. Few problems with the KHQ were noted although the performance of the personal relationships domain was complicated by the 'not applicable' response category. Psychometric testing supports the reliability and validity of the KHQ as an OAB-specific measure of HRQoL.",2003.0,0,0
230,12809928,Effectiveness of vaginally administered oxybutynin on rabbit bladder function.,Robert M Levin; Catherine Whitbeck; Abby Borow; Opal Burden; Robert E Leggett,"To demonstrate the effectiveness of vaginally delivered oxybutynin on bladder function. Oxybutynin has been used for treatment of urge urinary incontinence for more than 20 years. Thirty female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized, and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for both monitoring of bladder pressure and cystometry. After initial cystometry, acetylcholine (ACh) was injected into the vesical artery at 15-minute intervals for 4 hours. Cystometry was performed at the 2-hour mark and at the end of each experiment (4 hours). After the third ACh administration, vaginal or oral oxybutynin was given and the effect on the response to ACh, blood pressure, and cystometry was observed. The high dose of oxybutynin completely inhibited the response to ACh and significantly inhibited the micturition reflex. A 45% inhibition of micturition pressure occurred at the intermediate dose. Little effect on compliance after the low dose and a significant increase in compliance after the mid-dose occurred. Both the low and intermediate doses of oxybutynin reduced the response to ACh to approximately 50% of control. No blood pressure effects of vaginal oxybutynin were noted for any concentration. Oral oxybutynin showed very similar effects to that of the intermediate vaginal dose. Vaginally delivered oxybutynin was effective in decreasing bladder compliance and inhibiting intra-arterial ACh-stimulated bladder contractions with little or no effect on the vascular effect of ACh.",2003.0,0,0
231,12811292,Recent developments in the management of detrusor overactivity.,Vivek Kumar; Lucy Templeman; Christopher R Chapple; Russell Chess-Williams,"Detrusor overactivity is a relatively common yet embarrassing symptom complex with significant impact on quality of life. The mainstay of current pharmacological treatment involves use of muscarinic receptor antagonists, but their therapeutic efficacy is limited by their troublesome side effects resulting in the non-continuance of treatment in a significant number of patients. Therefore, the development of new drugs can proceed by targeting alternative pathways affecting detrusor overactivity. In this article, the pharmacological basis for the current therapeutic alternatives for managing detrusor overactivity and possible future developments are discussed. It is clear that far from being a passive container for urine, the urothelium is a crucial part of the bladder. Its functions are complex, dynamic and important, and only now becoming understood. The release of ATP from urothelium in response to distension and its action on P2X receptors resulting in activating both motor and sensory neurons is being increasingly recognised. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction. However, in functionally abnormal bladders, a non-cholinergic activation via the purinergic receptors may occur. The central nervous mechanisms controlling the micturition reflex have also recently attracted attention. Recent research has suggested that several transmitters may modulate voiding. However, few drugs with clinical benefits have been developed so far. Present treatments for overactive bladders have significant non-compliance rates. Hopefully, future research will lead to drugs with greater therapeutic benefits and better tolerance.",2003.0,0,0
232,12811297,Posterior urethral valves: lessons learned over time.,Kenneth I Glassberg,,2003.0,0,0
233,12811500,"Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability.",M Halaska; G Ralph; A Wiedemann; G Primus; B Ballering-Brühl; K Höfner; U Jonas,"Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in patients with urge syndrome. The trial comprised a total of 358 patients with urge syndrome or urge incontinence. After randomisation in the ratio of 3:1, participants were treated continuously for 52 weeks with either trospium chloride (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks, patients were physically examined with measurements of blood pressure and pulse rate, were questioned about any adverse events, checked for compliance and underwent relevant laboratory tests. As an additional safety measure, an ECG was made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning, and at 26 and 52 weeks to determine the maximal cystometric bladder capacity. Among others things, the frequencies of micturition, incontinence and number of urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52. The evaluation of vital parameters, laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics. Analysis of the micturition diary clearly indicated a reduction of the micturition frequency, incontinence frequency, and a reduction of the number of urgencies in both treatment groups. Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks (P=0.001). Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs. Adverse events occurred in 64.8% of the patients treated with trospium chloride and 76.7% of those treated with oxybutynin. The main symptom encountered in both treatment group was dryness of the mouth. For patients on trospium chloride, the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth, resulting in a considerably lower risk during treatment given with trospium chloride than with oxybutynin (0.045 and 0.021, respectively). An overall assessment for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability.",2003.0,1,1
234,12837438,Oxybutynin for diagnosis of infravesical obstruction in boys with urinary incontinence.,Laetitia M O de Kort; Aart J Klijn; Pieter Dik; Cuno S P M Uiterwaal; Tom P V M de Jong,"To investigate whether good suppression of symptoms during anticholinergic therapy in boys with urinary urge incontinence is correlated with anatomic infravesical obstruction. In a prospective study, 65 boys with urge incontinence were treated temporarily with anticholinergics. The effect of therapy was assessed, and a full video-urodynamic evaluation was performed. When obstruction could not be excluded urodynamically, urethrocystoscopy was done to assess the level and severity of obstruction, followed by endoscopic treatment. The effect of oxybutynin on incontinence was compared with the presence or absence of obstruction. In 49 of 65 boys aged 4 to 14 years with daytime urge incontinence, infravesical obstruction was found. Of the 49 boys, 38 (76%) had a good response to anticholinergic therapy. Of the 16 boys without infravesical obstruction, 12 (75%) did not improve with anticholinergic therapy. When anticholinergic therapy was used as a diagnostic test for infravesical obstruction, we found a positive predictive value and negative predictive value of 90% (95% confidence interval 74% to 96%) and 52% (95% confidence interval 31% to 73%), respectively. The effect of anticholinergic therapy on urge incontinence can be used as a diagnostic test to differentiate between anatomic infravesical obstruction and other causes of incontinence in boys.",2003.0,0,0
235,12893326,Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence.,Roger R Dmochowski; Peter K Sand; Norman R Zinner; Marc C Gittelman; G Willy Davila; Steven W Sanders; Transdermal Oxybutynin Study Group,"To compare the efficacy and safety of an oxybutynin transdermal delivery system (OXY-TDS) and oral, long-acting tolterodine (TOL-LA) with placebo in previously treated patients with urge or mixed urinary incontinence. After withdrawal of their current antimuscarinic therapy, 361 adult patients were randomized to 12 weeks of double-blind, double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day, daily TOL-LA 4 mg, or placebo. Evaluations included change from baseline in patient urinary diary symptoms, incontinence-specific quality of life, and safety. OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes (median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo; P <0.05), increased the average void volume (median change 24 and 29 mL versus 5.5 mL, P <0.01), and improved quality of life (incontinence impact questionnaire [IIQ] total score, P <0.05; Urogenital Distress Inventory Irritative Symptom subscale, P <0.05) compared with placebo. The most common adverse event for OXY-TDS was localized application site pruritus (14% versus 4% placebo) accompanied by a low incidence of systemic side effects (eg, dry mouth 4.1%). Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment (dry mouth 7.3% versus 1.7% placebo, P <0.05). OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence. OXY-TDS improves systemic safety with regard to anticholinergic side effects. Local skin irritation occurs in some OXY-TDS patients.",2003.0,0,0
236,12908692,Epidural spinal cord stimulation for neurogenic bladder.,Tasuku Wainai; Norimasa Seo; Takanori Murayama; Yuki Sato; Masaaki Sato,,2003.0,0,0
237,12930432,Tolterodine is equally effective in patients with mixed incontinence and those with urge incontinence alone.,K J Kreder; L Brubaker; T Mainprize,"To examine the efficacy of tolterodine, an antimuscarinic agent with a bladder-selective profile, in patients with mixed incontinence (MI, stress and urge) compared with patients with urge incontinence (UI) alone. The study included 239 patients with MI (urge predominating) and 755 with urge incontinence alone from a single-blind, multicentre trial of 1380 patients (80% female) with an overactive bladder. Those completing the trial were analysed 'per-protocol'. After a 7-day washout and a 3-day run-in to collect baseline information, patients were treated with tolterodine twice daily for 16 weeks. The two groups were compared for incontinence episodes/24 h, voiding frequency, nocturia episodes and pad usage after 16 weeks of treatment. After 16 weeks the median changes from baseline for all voiding variables were statistically significant for the MI and the UI groups (P < 0.001), with no apparent significant between-group differences. The median percentage reduction in incontinence episodes from baseline was 67% for the MI and 75% for the UI groups (P = 0.39). 'Dry' rates for the MI and UI groups at the end of the study were 39% (66/171) and 44% (243/552), respectively, whilst 24% of patients in each group (MI 40/170; UI 130/551) achieved a voiding pattern of < 8 voids/24 h. 'Cure' rates for nocturia and the reduction in the number of patients not using pads used were also similar between the groups. Tolterodine is as effective in reducing leakage and other symptoms of an overactive bladder in patients with MI as it is in patients with UI alone.",2003.0,0,0
238,12930445,Pharmacokinetic fixes for pharmacodynamic deficits.,M Wyllie,,2003.0,0,0
239,12934775,Advances in medical management of overactive bladder.,Elliott Richelson; Daniel S Elliott,,2003.0,0,0
240,12934777,"Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial.",Ananias C Diokno; Rodney A Appell; Peter K Sand; Roger R Dmochowski; Bernard M Gburek; Ira W Klimberg; Sherron H Kell; OPERA Study Group,"To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.",2003.0,0,0
241,12934778,"Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects.",Rodney A Appell; Michael B Chancellor; R Howard Zobrist; Heather Thomas; Steven W Sanders,"To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments. Between October 15 and November 6, 2001, 13 healthy subjects (7 men and 6 women) participated in a randomized, 2-way crossover study of transdermal (Oxytrol, 3.9 mg/d) and extended-release oral (Ditropan XL, 10 mg) oxybutynin. Multiple blood and saliva samples were collected. Pharmacokinetic parameters and total salivary output were assessed. Statistical analyses included 95% confidence intervals, paired t test, analysis of variance, and linear regression. Steady-state plasma concentrations were achieved after the first transdermal application and after the second extended-release oral dose. Mean +/- SD 24-hour oxybutynin areas under the concentration-time curve were comparable during transdermal and oral extended-release treatments, 10.8 +/- 24 vs 9.2 +/- 33 ng x h(-1) x mL(-1), respectively. However, the ratio of area under the curve (N-desethyloxybutynin/oxybutynin) after transdermal administration (1.2 +/- 03) was significantly lower (P < .001) than after extended-release oral administration (4.1 +/- 0.9). Mean plasma concentrations were less variable during transdermal compared with extended-release oral administration. Mean +/- SD saliva output was greater during transdermal than extended-release oral treatment (15.7 +/- 93 vs 12.2 +/- 6.8 g, respectively; P = .02). Lower N-desethyloxybutynin during transdermal application was associated with greater saliva output (r = -059, P = .04). No clinically important treatment-related adverse effects were observed. Transdermal oxybutynin administration results in greater systemic availability and minimizes metabolism to N-desethyloxybutynin compared with extended-release oral administration. Lower N-desethyloxybutynin plasma concentration and greater saliva output during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder.",2003.0,0,0
242,12962951,Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine.,Robert Freeman; Simon Hill; Richard Millard; Mark Slack; John Sutherst; Tolterodine Study Group,"To evaluate the effect of once-daily, extended-release tolterodine on urinary urgency in patients with overactive bladder. Patients with urinary frequency (eight or more micturitions per 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral treatment with tolterodine extended release 4 mg once daily (n=398) or placebo (n=374) for 12 weeks. Efficacy was assessed by use of patient perception evaluations. The results presented are a secondary analysis of this double-blind, placebo-controlled study. Of patients treated with tolterodine extended release, 44% reported improved urgency symptoms (compared with 32% for placebo), and 62% reported improved bladder symptoms (placebo, 48%) (both P<.001 compared with placebo). The odds of reducing urgency and improving bladder symptoms were 1.68 and 1.78 times greater, respectively, for patients in the tolterodine extended release group than for patients receiving placebo. In response to urgency, there was a more than six-fold increase in the proportion of patients able to finish a task before voiding in the tolterodine extended release group. The proportion of patients unable to hold urine upon experiencing urgency was also decreased by 58% with tolterodine, compared with 32% with placebo (P<.001). The proportion of patients reporting ""much benefit"" from treatment was greater for tolterodine extended release than for placebo (43% versus 24%; P<.001). The only adverse events with an incidence of greater than 5% were dry mouth, headache, and constipation, with only dry mouth markedly more frequent with tolterodine than with placebo. Tolterodine extended release has demonstrable efficacy in reducing the severity of urinary urgency and is associated with improvements in overactive bladder symptoms that are meaningful to patients.",2003.0,1,1
243,12967534,,,,,0,0
244,14499063,Update on overactive bladder: pharmacologic approaches on the horizon.,Eric S Rovner; Alan J Wein,"Limitations exist with regard to the array of available agents for the pharmacologic therapy of overactive bladder, including issues of efficacy and tolerability. It is clear that the ideal agent for this condition has not been identified. However, several new pharmacologic treatments, including some with novel approaches to drug delivery, have emerged in clinical development over the past few years. These agents include a variety of anticholinergics and others. In initial studies, some of the agents appear to compare favorably with existing therapies. Whether these promising results will hold up when subjected to large-scale, well-controlled clinical trials is unclear.",2003.0,0,0
245,14501691,Does treatment with clean intermittent catheterization in boys with posterior urethral valves affect bladder and renal function?,G Holmdahl; U Sillen; A-L Hellström; R Sixt; E Sölsnes,"In boys with resected posterior urethral valves (PUV) deterioration of renal function is seen during childhood and adolescence, which may partly be caused by bladder dysfunction. We present data on renal and bladder function initially and at followup of boys with PUV in whom the bladder dysfunction has been treated since infancy. The study included 35 boys with PUV. Bladder regimen, including early toilet training from the age of 1.5 years and detrusor relaxant drugs for the treatment of incontinence from ages 4 to 6 years, was introduced to all patients. A total of 19 boys were started on clean intermittent catheterization (CIC) at a median age of 8 months due to pronounced bladder dysfunction with poor emptying, unsafe pressure levels, high grade reflux and renal impairment. No serious complications of CIC have been seen during followup. Of the 19 boys 2 stopped performing CIC due to noncompliance of the parents at 1 and 3 years, respectively. Initial renal function, measured as median glomerular filtration rate (GFR) in percent of expected for age, was 60% in the CIC group and 90% in the nonCIC group. At followup at a median age of 8 years the CIC group (n = 14, 3 transplanted boys excluded) had an increase in median differential GFR (difference between followup and initial GFR) of 7% (p <0.01), which was similar increase to that of the nonCIC group. In the 2 boys who stopped performing CIC renal function deteriorated with a median differential GFR of -24%. In the CIC group detrusor instability decreased. Poor compliance was seen in 6 of the 19 boys initially and only one remained poorly compliant. In 1 of the boys who stopped performing catheterization a low compliant bladder developed. In all of the other cases bladder capacity increased more than expected for age. The results suggest that treatment of bladder dysfunction in boys with PUV can counteract the deterioration in renal function seen during childhood but the number of patients in our study is limited.",2003.0,0,0
246,14532838,Trospium chloride for the treatment of detrusor instability in children.,P Lopez Pereira; C Miguelez; J Caffarati; F Estornell; A Anguera,"We assessed the efficacy and most appropriate dosage of trospium chloride (TCl) for managing bladder instability in children as compared with a placebo. A total of 58 patients with bladder instability were allocated at random to 1 of 5 groups-10, 15, 20 or 25 mg TCl, or placebo administered daily in a multicenter, randomized, single-blind clinical study. Patients were treated for 21 days, and current symptoms, voiding diary and urodynamic values were collected at the beginning and end of the treatment period. All adverse events were recorded at the last visit. Of 50 patients treated with TCl 41 (82%) had a positive therapeutic result (excellent, good or fair) versus only 3 of 8 patients with improvement in the placebo group (37.5%, p = 0.006). In all responding patients clinical symptoms either resolved or decreased markedly, and in 37 (74%) this improvement was accompanied by urodynamic improvement. In these 37 children the average number of uninhibited contractions decreased by 54.3% (p <0.0001) and the volume at first contraction increased by 71.4% (p = 0.001). There were no statistically significant differences with regard to therapeutic efficacy between TCl dosages. Fourteen patients (9 with TCl, 5 with placebo) showed no clinical improvement, although some had improved urodynamic parameters. Furthermore, TCl was well tolerated with few patients (10%) experiencing adverse effects. Trospium chloride (10 to 25 mg total daily dosage, split into 2 doses) is an effective option for the management of detrusor instability in children.",2003.0,0,0
247,14565094,[Non-coordinated micturition syndrome mimicking posterior urethral valves in a male neonate].,R Martín-Crespo Izquierdo; R Luque Mialdea,"High-grade of vesicoureteral reflux (VUR) has been reported in association with prenatal diagnosis of abnormal bladder function in a male neonate with postpatally no anatomical urethral obstruction and bladder dysfunction. This study was designed to describe clinical presentation of this entity in male neonates, the urodynamic pattern, prognosis in terms of renal function and therapeutic management since birth, in our experience with four cases. We reviewed the records of 4 male neonates diagnosed at birth of bilateral high-grade VUR (grade > or = 4) with prenatally diagnosed hydronephrosis; thus 8 refluxing renal units (RRU) were studied. All cases had renal failure at birth. In all cases dimercaptosuccinic acid (DMSA) renography was performed. All RRU had reflux nephropathy; 5 RRU had moderate impairment of renal function (20-40%). In 3 RUU was demonstrated by a severe decrease in renal function (10-20% in 2 RUU, and less than 10% in 1 RUU). Micturating cystouretrography (MCUG) excluded the presence of posterior urethral valves; however, in all cases a tightened bladder neck (""bladder neck impression"") was present. Endoscopy was performed in one baby excluding posterior urethral valves. Follow up ranged from 2 to 5 years (mean 3.5). In all 4 cases underwent transient urinary diversion during their first month of life. Urodynamic study revealed a high-risk bladder with low compliance, a reduced functional bladder capacity and a high residual urine volume in all cases. All the patients was placed on antibiotic prophylaxis and oral oxybutinin chloride. Three patients underwent bilateral Cohen ureteral reimplantation. The other boy underwent left nephrectomy, right Politano ureteral reimplantation and ureterocystoplasty. In the 7 RRU postoperative MCUG revealed cessation of reflux. Currently therapy includes antibiotic prophylaxis in 4, oral oxybutinin in 4 and intermittent catheterisation in 2 patients. 3 patients have normal renal function. The other boy underwent re-diversion because of renal failure. Fetal severe bilateral reflux nephropathy is a clinical entity almost exclusively in male neonate mimicking hyper-pressure syndrome due to urethral obstruction, in terms of evolution (to chronification and renal failure) and treatment (that requires primordial management of bladder dysfunction). Absence of anatomical urethral obstruction and urodynamic pattern suggest functional obstruction of bladder neck-periurethral sphincter complex in fetal life as a cause for this syndrome. For this reason we consider it as a clinical presentation of fetal non-coordinated voiding in male or ""posterior urethral valves like syndrome"".",2003.0,0,0
248,14567008,Sexuality and disease.,John E Morley; Syed H Tariq,"Disease is commonly associated with sexual dysfunction in both men and women. In many cases, effective treatments are available that can improve libido, erectile dysfunction, and vaginal dryness. Sexual problems in older persons with disease often lead to anxiety, marital discord, and withdrawal. It is the responsibility of all health care professionals to inquire about sexuality in all patients, no matter what the patient's age, and to be aware that frailty [79-81] is not, in itself, a barrier to sexuality. Health professionals need to give education, support, and counseling on sexuality for patients with disease.",2003.0,0,0
249,14587130,Evaluation and management of urinary incontinence in elderly women.,Christine A LaSala; George A Kuchel,"Urinary incontinence is a common problem among older women, with a great impact on their quality of life, self-esteem and ability to live independently. Although often neglected by both patients and health-care providers, a variety of behavioral, pharmacologic and surgical interventions are now available to resolve or improve the symptoms of most older women who are incontinent. Since many of the factors which contribute to continence in late life lie outside of the bladder, the assessment of urinary incontinence in older women must extend beyond the genitourinary tract, assessing domains such as mobility, fluid balance and cognition. The primary care physician in uniquely placed in being able to diagnose this problem, to initiate treatment in many patients and to refer those requiring additional specialized expertise.",2003.0,0,0
250,14616458,"Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial.",Y Homma; J S Paick; J G Lee; K Kawabe; Japanese and Korean Tolterodine Study Group,"To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB). Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed. In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients. Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.",2003.0,0,0
251,14657444,Transient memory impairment and hallucinations associated with tolterodine use.,Jack W Tsao; Kenneth M Heilman,,2003.0,0,1
252,7484484,Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial.,G Szonyi; D M Collas; Y Y Ding; J G Malone-Lee,"The aim of this study was to examine the efficacy of oxybutynin plus bladder training in the treatment of detrusor instability in frail elderly patients living independently in the community. It was a randomized, double-blind, placebo-controlled parallel-group trial of oxybutynin in 57 elderly patients (mean age 82.2, SD 6.06), with frequency and incontinence due to detrusor instability. After a 2-week run-in period patients received a bladder training and drug or placebo for the next 6 weeks. Outcome measures were changes in frequency and incontinence, recorded throughout on diary charts, and subjective evaluation of symptoms ('better'/'not better', and using a four-point scale 'cure' to 'no change'). Oxybutynin was superior to placebo in reducing daytime frequency [95% confidence interval (CI) of difference in change in frequencies totalled over 14 days was -27.0, -6.0; p = 0.003] and in producing subjective benefit (at day 29 only), when 24/28 (86%) patients on oxybutynin described benefit compared with 16/29 (55%) on placebo (p = 0.02). There was no difference between the groups in reduction of incontinent episodes. The median dose of oxybutynin titrated for therapeutic effect was 5 mg/day, and for placebo 10 mg/day (CI of difference 0.001, 5.001; p = 0.05). Side-effects reported were of similar frequency (50%) in the two groups. We conclude that oxybutynin with bladder training is superior to bladder training alone in reducing frequency due to detrusor instability in very elderly people living at home.",1995.0,1,1
253,7497872,Hypoglycemia following inadvertent and factitious sulfonylurea overdosages.,D C Klonoff; B J Barrett; M S Nolte; R M Cohen; R Wyderski,"To recognize unreported sulfonylurea overdosages in hypoglycemic patients. We describe three patients with hypoglycemia due to inadvertent (in two patients) and factitious (in one patient) sulfonylurea overdosages. We review the world literature and summarize 43 previously published cases of inadvertently administered and 23 previously published cases of factitiously self-administered sulfonylurea overdosages with hypoglycemia. An inadvertently administered fulsonylurea overdosage usually occurred when a sulfonylurea was accidentally substituted for an intended medication with a similar generic or trade name. Features of the patients with a factitiously self-administered sulfonylurea overdosage included: 1) a history of the patient or patient's spouse having a medical job or sulfonylurea-treated diabetes mellitus; 2) an unusual affect or psychiatric history; 3) an abrupt onset of severe symptoms without previous milder symptoms; and 4) an absent hypoglycemic or hyperinsulinemic response to provocative testing. These features are not typical for an insulinoma. When a hypoglycemic patient denies antidiabetic medication use, we recommend sequentially performing: 1) a thorough pill inspection; 2) an interview for recently altered pill appearances; 3) a measurement of serum insulin and C-peptide levels during hypoglycemia; and 4) a blood or urine sulfonylurea screen. Discovery of an unreported sulfonylurea overdosage can eliminate the need to search for an insulinoma and prevent further overdosages from occurring.",1995.0,0,0
254,7562241,Analysis of whole-blood cyclosporin G by liquid chromatography in renal transplant recipients.,J H McBride; S S Kim,"Cyclosporin G (CsG) is less nephrotoxic than Cyclosporin A (CsA) and is undergoing clinical trials for use as an immunosuppressive agent after renal transplantation. In this study, CsG was measured by a rapid high-performance liquid chromatography (HPLC) technique in blood samples (n = 107) received from renal transplant recipients. The HPLC assay proved to be analytically suitable in that it was sensitive, linear, and precise and had high recovery (102%). However, interference was observed from some potentially co-administered drugs such as calcitriol, ferrous sulfate, hydrazaline, and minoxidil. The HPLC assay for CsG correlated well with a FPIA (Abbott TDx), FPIA = 0.964 (HPLC) + 33.59, r = 0.9819, Sy/x = 36.66 for patients receiving a low dose of CsG (5 mg/kg/day) and a high dose (10 mg/kg/day). Furthermore, the HPLC technique was capable of measuring predictable CsG concentrations when the drug was tapered to lower doses at various stages of the 16 week clinical trial. The HPLC for CsG has the further advantage that the same system and mobile phase can be used to measure CsA while using CsC as the interval standard.",1995.0,0,0
255,7607378,[Topical administration of oxybutynin hydrochloride in women with urge incontinence. Results of a prospective randomized double-blind study].,H Enzelsberger; C Kurz; H Helmer; F Mittermayer,Detrusor instability is the second most common cause of femal urinary incontinence. Oxybutynin chloride anticholinergic action with direct muscle-relaxant properties. 39 women with persistent-urgeincontinence participated in a pilot study of intravesical oxybutynin application. Patients received either 20 mg oxybutynin or placebo as 40 ml sterile sodium chloride solution administered intravesically over a period of 10 days. Urodynamic assessment as well as micturition protocols were performed before and after treatment. The intravesical oxybutynin-application was significantly better than the placebo application concerning reduction of pollakisuria and nycturia. Oxybutynin also increased bladder capacity more than in the placebo-treated group (p < 0.01) and provided an improvement of bladder compliance (p < 0.05). No local or systemic side effects were observed which would have immediately terminated the oxybutynin treatment.,1995.0,0,0
256,7613803,The Kropp-onlay procedure (Pippi Salle procedure): a simplification of the technique of urethral lengthening. Preliminary results in eight patients.,P D Mouriquand; R Sheard; N Phillips; J White; S Sharma; C Vandeberg,"To lengthen the urethra to increase bladder outlet resistance in adolescent girls with a neurogenic bladder. During a 2-year period (1992-94), eight girls (mean age 13.5 years, range 9-19) underwent a Kropp-onlay urethral lengthening associated, for six of them, with a bladder augmentation. Seven of the eight patients patients were spina bifida and confined to a wheelchair. One patient had had a previous transverse myelitis. A Benchekroun hydraulic value (in three cases) and a Malone procedure (in two cases) were performed at the same stage. The technique of Kropp-onlay urethral lengthening, which creates a flap value mechanism which leaks when the bladder is too full, is described and illustrated. Seven of eight patients were dry during the day and four were occasionally damp during the second part of the night. One could not be dry for more than 2 h during the day but had a very hyperactive detrusor. She developed two bladder stones which required an open vesicotomy. One developed a urethral fistula requiring a second Kropp-onlay procedure and became dry afterwards. Two patients, who did not undergo a bladder augmentation, needed oxybutinin therapy to obtain a satisfactory result. Post-operative urodynamic measurements are discussed. The Knopp-onlay urethral lengthening is easier to perform than the original Kropp procedure. The preliminary results are similar to those of alternative techniques (e.g. urethral suspension) but long-term reliability of this technique remains unknown.",1995.0,0,0
257,7620236,,,,,0,0
258,7771021,In support of behavioral treatment for day wetting in children.,J L Edens; R S Surwit,,1995.0,0,0
259,7775717,Does oxybutynin add to the effectiveness of prompted voiding for urinary incontinence among nursing home residents? A placebo-controlled trial.,J G Ouslander; J F Schnelle; G Uman; S Fingold; J G Nigam; E Tuico; B B Jensen,"To determine if oxybutynin, a bladder relaxant medication, adds to the effectiveness of prompted voiding (PV) in the management of urinary incontinence among nursing home residents. Randomized, placebo-controlled, double-blinded, dose-adjusted, crossover trial of oxybutynin added along with PV. Seven nursing homes in Los Angeles County, California. Seventy-five nursing home residents with predominantly urge incontinence, whose incontinence did not respond well to a trial of PV. The frequency of incontinence, measured as the percentage of hourly (7 AM to 7 PM) physical checks over a 3-day period at which the resident was found wet. Sixty-three (84%) of the residents completed the study. Among those completing the trial, the percent of checks wet went from 26.5% to 23.7% on placebo to 20.2% on active drug. These changes were statistically significant but not clinically meaningful. A clinically significant decrease in the frequency of incontinence, which we defined as a relative reduction in the percent of checks wet of > 33%, occurred in 20 subjects (32%) while on active drug and in 12 subjects (19%) while on placebo (P = .48 by chi-square). Twenty-five subjects (40%) met our ""continence criteria"" of an average of one or less wet per day while on active drug, and 11 subjects (18%) achieved this goal on placebo (P = .005 by chi-square). Oxybutynin does not add to the clinical effectiveness of PV in the majority of nursing home residents with urge type urinary incontinence. Selected residents may, however, become more responsive to PV while on oxybutynin. Our data are consistent with other studies of bladder relaxant medications in functionally impaired populations. New drugs and/or other interventions are needed for the large number of incontinent nursing home residents who do not respond well to PV.",1995.0,1,1
260,7788250,Nocturnal enuresis.,S D Mark; J D Frank,"Nocturnal enuresis is common. Although its aetiology remains unclear recent evidence increasingly supports the lack of a normal nocturnal increase in ADH leading to nocturnal polyuria exceeding functional bladder capacity. Sleep patterns are probably normal although an arousal disorder might be a factor. Treatment should follow careful evaluation to determine if one is dealing with 'uncomplicated' or 'complicated' enuresis. Complicated enuresis requires further investigation. 'Uncomplicated enuresis' always requires reassurance and patient and parent education. Resource centres such as ERIC can provide information and advice. Active treatment should be tailored to the patients age, motivation and parental wishes. Behavioural modification techniques yield the highest long-term cure rate but require the most commitment and are rarely successful before the age of 7-8 years. Pharmacotherapy has been revolutionized by DDAVP which gives a response rate of up to 70% relatively free from side-effects but at the price of a high relapse rate after medication. Imipramine is less expensive than DDAVP but may be fatal in overdose. Anticholinergics should be reserved for those patients with significant diurnal symptoms or those who fail first-line pharmacotherapy. Overall patients and parents should be reassured by the high spontaneous cure rate.",1995.0,0,0
261,7788255,"Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia.",H Madersbacher; M Stöhrer; R Richter; H Burgdörfer; H J Hachen; G Mürtz,"To compare trospium chloride (TCl), a quaternary ammonium derivative with atropine-like effects and predominantly antispasmodic activity, with oxybutynin (Oxy) in terms of efficacy and adverse effects. In a randomized, double-blind, multicentre trial, 95 patients with spinal cord injuries and detrusor hyper-reflexia were studied. Treatment consisted of three doses per day over a 2 week period, with either Oxy (5 mg three times daily) or with TCl (20 mg twice daily) with an additional placebo at midday. The results were evaluated with regard to changes in objective (urodynamic) data and subjective symptoms as well as the incidence/severity of adverse effects. With both drugs there was a significant increase in maximum bladder capacity, a significant decrease in maximum voiding detrusor pressure and a significant increase in compliance and residual urine; there were no statistically significant differences between the treatment groups. The percentage of patients who reported severe dryness of the mouth was considerably lower (4%) in those receiving TCl 2 x 20 mg/day than in those receiving Oxy (23%) 3 x 5 mg/day. Withdrawal from treatment was also less frequent in those receiving TCl (6%) than in those receiving Oxy (16%). Trospium chloride and oxybutynin, judged in terms of objective urodynamic parameters, are of substantially equal value as parasympathetic antagonists. However, assessment of tolerance in terms of adverse drug effects showed that TCl had certain advantages.",1995.0,1,1
262,7824373,Intravesical oxybutinin chloride in children with intermittent catheterization: sonographic findings.,J M Zerin; M A DiPietro; M L Ritchey; D A Bloom,"The sonographic findings in the bladder are presented in four children with myelomeningocele and neurogenic dysfunction of the bladder, who were treated with intermittent self-catheterization and intravesical oxybutinin chloride. All were referred for routine sonography of the urinary tract. Each had infused a crushed tablet of oxybutinin chloride intravesically 30-120 min before the examination. In two children, brightly echogenic, non-shadowing particles were suspended in the bladder urine. In one of these, the particles swirled giving the impression of a ""snowstorm""; in the other, most of the particles gradually settled forming an irregular clump on the bladder base. In the remaining two children, the urine appeared diffusely hazy with innumerable tiny particles giving the impression of a fine mist filling the bladder. The sonographic appearance of the urine in the bladder after intravesical instillation of crushed tablets can be dramatic and can simulate pus, blood, fungus, or other debris in the bladder lumen. In the absence of clinical symptoms or hematuria, a history of recent infusion of medication into the bladder should be sought.",1994.0,0,0
263,7856993,Incontinence in the nursing home.,J G Ouslander; J F Schnelle,"Urinary and fecal incontinence are prevalent, disruptive, and expensive health problems in the nursing home population. Nursing home residents who are incontinent of urine should have a basic diagnostic assessment, including a focused history and bladder record, a targeted physical examination, a urinalysis, and a determination of postvoid residual urine volume done by catheterization or ultrasonography. Potentially reversible conditions, such as fecal impaction and drug side effects, should be identified and treated. Selected residents should have further urodynamic evaluation or other diagnostic tests. Prompted voiding, a simple, noninvasive behavioral intervention, is effective in managing daytime urinary incontinence in one quarter to one third of incontinent nursing home residents. If it is to be effective over a long period of time, this intervention must be targeted to those residents most likely to respond. Selected nursing home residents will benefit from other behavioral interventions, drug therapy, or surgery. Because of the morbidity associated with it, long-term catheterization should only be used for specific indications. Like urinary incontinence, fecal incontinence may be caused by potentially reversible conditions. After such conditions have been excluded, fecal incontinence can generally be managed effectively by avoiding fecal impaction and by using a systematic bowel-training protocol.",1995.0,0,0
264,7875185,Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers.,A Pietzko; W Dimpfel; U Schwantes; P Topfmeier,"Trospium chloride and oxybutynin are two antimuscarinergic agents used in the treatment of unstable bladder, urge incontinence, combined stress urge incontinence and detrusor hyperreflexia. The possibility that these two drugs produce changes in central nervous electrical activity was examined in an open, prospective, phase I study involving 12 volunteers. Quantitative evaluation of the multichannel electroencephalogram obtained from young healthy volunteers showed statistically significant decreases in alpha and beta 1 activity after oxybutynin, but not after intravenous or oral administration of trospium chloride. The biological activity of both drugs was ascertained by continuous simultaneous recording of the heart rate. A decrease in heart rate was detected after oral administration of oxybutynin, and an increase was seen after i.v. administration of trospium chloride. The results suggest that trospium chloride is less likely to produce central nervous adverse effects than to oxybutynin.",1994.0,0,0
265,7912347,Cladribine in treatment of chronic progressive multiple sclerosis.,J C Sipe; J S Romine; J A Koziol; R McMillan; J Zyroff; E Beutler,"Chronic progressive multiple sclerosis (MS) is a severely disabling demyelinating disease in which autoimmune processes seem to have a major role. The nucleoside drug cladribine is a potent lympholytic agent with few side-effects. We have studied its efficacy and safety in a randomised double-blind trial. 51 patients (48 entered as matched pairs) received four monthly courses of 0.7 mg/kg cladribine or placebo (saline) given through a surgically implanted central line. Neurologists with no knowledge of which medication the patient was receiving examined the patients monthly and noted two rating scale scores (Kurtzke and Scripps). Cerebrospinal fluid and brain magnetic resonance imaging (MRI) examinations were done at 6 and 12 months. Average neurological scores, demyelinated volumes on MRI, and concentrations of oligoclonal bands in cerebrospinal fluid were stable or improved in the patients receiving cladrabine but continued to deteriorate in patients on placebo. Mean paired (placebo minus matched cladribine) differences at 12 months relative to baseline were 1.0 (SE 0.4) for the Kurtzke scores, -13.9 (2.3) for the Scripps scores, 4.57 (1.17) mL for demyelinated volumes, and 7.3 (3.3) arbitrary units for concentrations of oligoclonal bands. Cladribine was generally well tolerated and clinically significant toxicity occurred in only 1 patient, in whom severe marrow suppression developed with complete recovery after several months. 1 patient died of newly acquired hepatitis B, an event unlikely to be related to cladribine. We conclude that the immunosuppressive drug cladribine influences favourably the course of chronic progressive MS.",1994.0,0,0
266,8051758,The value of the vaginal pack test in large cystoceles.,G M Ghoniem; F Walters; V Lewis,"To detect possible stress urinary incontinence associated with but masked by large cystoceles protruding through the vaginal orifice, a vaginal pack test was done in conjunction with video fluoro-urodynamic studies. Sixteen female patients with large cystoceles did not demonstrate stress urinary incontinence on clinical examination and were included in this study. Additionally, 10 healthy female volunteers underwent the same test to study the effect of a vaginal pack on urethral dynamics. The vaginal pack revealed the presence of stress urinary incontinence in 11 patients (69%): 3 (19%) with type II (vesicourethral hypermobility) and 8 (50%) with type III (internal sphincteric deficiency). After insertion of the vaginal pack, urodynamic studies showed that the closing proximal urethral pressure in patients with stress urinary incontinence was significantly lower than in continent patients (p < 0.05). No significant change in urethral pressures was noted in volunteer subjects after vaginal pack insertion. Fluoroscopy showed kinking of the posterior urethra and enlargement of the most dependent portion of the cystocele, that is the lower half of the hourglass image. Our study suggests that the mechanisms of continence in these patients are multifactorial, including urethral kinking, urethral compression and pressure dissipation. The vaginal pack test is easy to perform, increases visualization of the vesicourethral unit when used with fluoroscopy, and can aid in the selection of patients who would benefit from anti-incontinence surgery and/or cystocele repair.",1994.0,0,0
267,8161462,[The tethered cord syndrome : a review of causes].,C Chong; J Molet; B Oliver; P Parés; P Tresserras; F Bartumeus,"We present eighteen cases with Tethered cord syndrome (TCS). They were eleven adults and eight children. There were eight cases with surgical interventions performed in other centers during the newborn period for different types of spinal disraphisms. Clinical onset was insidious in 88% of the cases, and in 12% of the cases was acute, due to a precipitating factor. The main clinical findings were neurological skeletal , urological and cutaneous alterations in variable frequencies. Magnetic resonance imaging (MRI) was the best diagnostic test. Urodynamic studies in patients with urological alterations were abnormal and they helped to establish additional pharmacological treatment. After surgery 88% of the patients had an improvement or an arrest in the progression of the symptoms. Patients with shorter duration of the symptoms (less than 2 years) had a better prognosis.",1994.0,0,0
268,8262104,Vasopressin deficiency in primary nocturnal enuresis. Results of a controlled prospective study.,J Steffens; M Netzer; E Isenberg; S Alloussi; M Ziegler,"The lack of circadian rhythmicity of plasma arginine vasopressin (AVP) in primary nocturnal enuresis (PNE) in some children is known. The original test protocol is time-consuming and needs excellent compliance by children and parents. The goals of the presented study are the introduction of a simple screening test and the evaluation of the response of treatment using intranasal synthetic vasopressin. Fifty-five children (aged 8.2 +/- 3.1 years) with PNE and 15 children (aged 7.9 +/- 2.4 years) of a control group were investigated. Using a standardized protocol, AVP levels were measured by radioimmunoassay (RIA) under controlled water intake 3 times per day over a period of 72 h. Fourteen of 55 tested children (25.5%) with PNE had a significant decrease in nocturnal AVP when compared to the control group. We measured also an increased nocturnal urine volume and a lower urine osmolality in this enuretic group. Eight of 14 patients (57.1%) with plasma AVP deficiency (AVPD) also had bladder instability. Nine of 14 patients (64.3%) with AVPD with or without concomitant bladder instability were totally dry during desmopressin treatment, but only 2 (14.3%) remained dry after discontinuation of treatment. Our data suggest that nocturnal urine osmolality measurement may reflect AVPD and predict a positive treatment outcome.",1993.0,0,0
269,8283381,Kegel exercises and childhood incontinence: a new role for an old treatment.,M S Schneider; L R King; R S Surwit,Kegel exercises were used to treat urinary incontinence in 79 children. An average of less than 2 hours of professional time was required. Incontinence was eliminated in 60% of the patients; children who had both day and night wetting tended to show simultaneous improvements in both problems. Research is needed to test the hypothesis that Kegel exercises eliminate involuntary contractions of the detrusor muscle.,1994.0,0,0
270,8299590,Characterization of the synthesis and secretion of transforming growth factor-alpha from salivary glands and saliva.,M G Humphreys-Beher; S P Macauley; N Chegini; G van Setten; K Purushotham; C Stewart; T T Wheeler; G S Schultz,"Whole saliva collected from rat, mouse, and human sources was found to contain high concentrations of transforming growth factor-alpha (TGF alpha) when analyzed by RIA. The concentrations of TGF alpha in unstimulated human saliva (age, 30-45 yr; n = 10; 1.5 +/- 3.1 nM) was reduced with age (age, 55-70 yr; n = 10; 0.4 +/- 0.1 nM), but increased in oral pathologies manifested in xerostomia (age, 57-70; n = 6; 0.8 +/- 0.2 nM) and Paget's disease (age, 58-76; n = 8; 2.0 +/- 0.6 nM). Immunohistochemical localization of TGF alpha in the salivary glands of rats and mice revealed specific immunostaining of the granular ductal cells of the parotid and submandibular glands. Reverse transcription followed by polymerase chain reaction amplification of total RNA from the parotid and submandibular glands of rats and mice demonstrated the presence of TGF alpha mRNA, suggesting endogenous synthesis by the salivary glands. Thus, salivary glands appear to be an exocrine source for a second member of the epidermal growth factor-like growth factor family in the oral cavity.",1994.0,0,0
271,8307445,Effect of the quaternary ammonium compound trospium chloride on 24 hour jejunal motility in healthy subjects.,T Schmidt; R Widmer; A Pfeiffer; H Kaess,"This study aimed to record 24 hour jejunal motility in healthy ambulant subjects and to analyse changes in motility caused by the oral administration of an anticholinergic agent, the quaternary ammonium compound, trospium chloride. In a placebo-controlled, double blind crossover trial, 24 hour jejunal motility was recorded in 12 healthy volunteers, aged 25 (21-30) years, using a digital data logger connected to two strain-gauge transducers mounted 20 cm apart in a flexible nasojejunal catheter. A computer program was developed to determine contraction parameters. Trospium chloride (15 mg orally thrice daily) prolonged the duration of irregular contractile activity after meals (p < 0.02) and reduced its contraction frequency and amplitude (p < 0.001). In the fasting state, the cycle length of the migrating motor complex was prolonged (p < 0.01) by an extended phase I (p < 0.025). Phase III was shortened (p < 0.005) and showed a slower aboral migration velocity (p < 0.005). Clustered contractions were less frequent during postprandial and fasting periods (p < 0.01). Runs of clustered contractions were completely absent with trospium chloride. Digital manometry was useful for long term recordings of jejunal motility and enabled the motor effects of an anticholinergic agent to be characterised in ambulant subjects.",1994.0,0,0
272,8536133,Augmentation duracystoplasty in neurogenic bladder dysfunction.,N Arikan; E Ozdiler; O Yaman; O Gögüs,"Augmentation cystoplasty is the treatment of choice for patients with neurogenic bladder dysfunction in cases that are unresponsive to other medical treatment. Although intestinal segments as bladder substitutes are preferred over the other alternatives at present, they are not ideal bladder replacements due to several potential hazards. The purpose of this study was to determine whether or not augmentation duracystoplasty can be an alternative to augmentation enterocystoplasties. Ten patients with neurogenic bladder dysfunction unresponsive to conservative measures, underwent augmentation duracystoplasty by using the modified Bramble-Clam technique. The follow-up period was T-28 months. At present, seven of 10 patients are completely continent for with clean intermittent catheterization. The remaining three patients required oral oxybutinin therapy, postoperatively, to achieve continence although lower dosages than those required in the preoperative period. We did not observe any serious pre- or postoperative complications. Based on these preliminary findings we think that duracystoplasty can be considered as a treatment alternative for hyperreflexic and/or low compliant neurogenic bladders.",1995.0,0,0
273,8575504,Intravesical application of oxybutynine: mode of action in controlling detrusor hyperreflexia. Preliminary results.,H Madersbacher; M Knoll,"Topical oxybutynine (Oxy) has been used successfully in neurogenic bladder patients who remained wet on oral anticholinergics or could not tolerate oral medication. However, little is known about the pharmacokinetics of intravesical Oxy. The aim of this study was to evaluate the resorption rate of intravesically given Oxy in the bladder in comparison with oral intake, and to find out which pharmacological properties of the drug are responsible for its effect when given intravesically. Our results indicate that peak plasma levels of intravesical Oxy appear later, are lower and stay longer compared to oral intake. Cystometries before, 20 min and 2 h after intravesical application of Oxy indicate that the main effect of intravesical Oxy on the detrusor is systemic due to its resorption. Our findings confirm the clinical experience that intravesical Oxy is well tolerated, very efficacious and better than oral medication.",1995.0,0,0
274,8588267,Flavoxate treatment of micturition disorders accompanying benign prostatic hypertrophy: a double-blind placebo-controlled multicenter investigation.,T L Dahm; P Ostri; J K Kristensen; S Walter; C Frimodt-Møller; R B Rasmussen; M Nøhr; N Alexander,"To investigate the effect of flavoxate (Urispadol) treatment on patients with symptomatic benign prostatic hypertrophy (BPH), with the main weight on the irritative symptoms, a randomized, double-blind, parallel-group, placebo-controlled and multicenter investigation was carried out. Seventy patients entered the study, 37 were allocated to flavoxate treatment on a daily dose of 1,200 mg (400 mg t.i.d.) for 12 weeks, and 33 patients were allocated to placebo treatment. In spite of a sufficient power, the study did not discriminate the two treatment groups in a statistically significant way (p > 0.05), when considering the main endpoints: the irritative symptom score and the global patient evaluation. Conservative treatment of micturition disorders accompanying BPH with flavoxate in doses of 1,200 mg/day cannot be recommended for clinical use.",1995.0,0,1
275,8632545,Post-prostatectomy incontinence: urodynamic findings and treatment outcomes.,G E Leach; B Trockman; A Wong; J Hamilton; F Haab; P E Zimmern,"We examined urodynamic findings and treatment outcomes in a large population of men with post-prostatectomy incontinence. A total of 215 men was referred for evaluation and treatment of significant post-prostatectomy incontinence. Urodynamic evaluation consisted of provocation multichannel medium fill cystometry with vigorous attempts to demonstrate incontinence. Treatment was directed by the results of the urodynamic study. A pad scoring system was used to gauge the severity of incontinence before and after treatment. Based on the results of urodynamic studies 40% of the men had genuine stress incontinence alone and approximately 60% had a major component of bladder dysfunction contributing to incontinence. Treatment results of 135 men demonstrated a significant decrease in pad score (p<0.001) for those treated with anticholinergics, those undergoing artificial sphincter insertion and those treated pharmacologically before sphincter placement. In our large series most men with prostatectomy incontinence did not have genuine stress incontinence alone. Thus, urodynamic studies are critical, not only to define cause of incontinence but to direct effective therapy.",1996.0,0,0
276,8698016,Ten years experience with chronic prostatitis in Africans.,G A Magoha,"This is a prospective study of seventy three patients with chronic prostatitis over a ten year period (1984-1994. The study was carried out at various hospitals in Lagos Nigeria and Nairobi Kenya. The mean age was 39.3 years. Chronic bacterial prostatitis was diagnosed in 15 patients (20.5%) of which 11 patients (73.3%) had Escherichia coli as the causative pathogen. Four of these patients (36.4%) were symptom and culture free after 12 weeks therapy with trimethoprimsulfamethoxazole. Four of the other seven patients not responding to trimethoprim (57.1%) became symptom and culture free after four weeks therapy with ciproflaxacin. Non bacterial prostatitis including prostatodynia was diagnosed in 58 patients (79.5%). Only 15 of these patients (25.8%) reported some subjective relief of symptoms on emperic therapy with doxycycline with complete relapse on discontinuation of therapy. Further therapy with non steroidal anti-inflammatory ibuprofen and anticholinergic oxybutinin chloride proved effective in alleviating symptoms in 40 patients (68.96%), but all relapsed on discontinuation of therapy emphasizing the ineffective and unsatisfactory nature of the present emperic treatment regimens as the cause of non bacterial prostatitis remains unknown.",1996.0,0,0
277,8701478,"Efficacy of oxybutynin, pseudoephedrine and indomethacin in the treatment of primary nocturnal enuresis.",B Varan; U Saatçi; S Ozen; A Bakkaloğlu; N Beşbaş,"The efficacy of oxybutynin, pseudoephedrine and indomethacin treatment was investigated in 29 patients with primary nocturnal enuresis. Patients were randomly assigned to either oxybutynin (1st group, n = 9), pseudoephedrine (2nd group, n = 11) or indomethacin (3rd group, n = 9) treatments. Oxybutynin and indomethacin did not cause a statistically significant difference in the number of dry nights (p > 0.05), but patients treated with pseudoephedrine had a significant increase in the number of dry nights (p < 0.05). Five patients in the oxybutynin and one patient in the indomethacin group experienced side effects. None of the patients in the pseudoephedrine group had any complaints with the drug. We therefore conclude that pseudoephedrine can be an alternative in the treatment of primary nocturnal enuresis.",1996.0,0,0
278,8737763,Effect of food on the bioavailability of oxybutynin from a controlled release tablet.,E Lukkari; P Castrèn-Kortekangas; A Juhakoski; E Löyttyniemi; K Aranko; P J Neuvonen,"The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20%. The Cmax of oxybutynin and N-desethyloxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.",1996.0,0,1
279,8826573,Phenazopyridine in urinary tract infections.,S A Zelenitsky; G G Zhanel,,1996.0,0,0
280,8849312,Comparison of the effects of various anticholinergic drugs on human isolated urinary bladder.,Y Wada; M Yoshida; K Kitani; H Kikukawa; A Ichinose; W Takahashi; S Gotoh; A Inadome; J Machida; S Ueda,"We investigated the effects of various anticholinergic drugs (atropine, oxybutynin, terodiline and propiverine) on the contractions induced by acetylcholine, KCl, CaCl2, and electrical field stimulation, in human isolated urinary bladder smooth muscles using the muscle bath technique. Urinary bladders were obtained from 20 patients who underwent total cystectomy due to malignant bladder tumor. The detrusor preparations were taken from the intact part of the dome of the bladder. Acetylcholine caused a concentration-dependent contraction in human detrusor preparations. Atropine (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-5) M), terodiline (10(-7)-10(-5) M) and propiverine (10(-7)-10(-5) M) caused parallel shifts to the right of the concentration-response curves to acetylcholine. The rank order of pA2 values was: atropine > oxybutynin > terodiline = propiverine. Atropine did not suppress the maximum contraction to acetylcholine, while the other drugs significantly suppressed the maximum contractions at the higher concentrations. Each drug caused a concentration-dependent inhibition of the KCl (80 mM)- and CaCl2 (5 mM)-induced contractions; the maximum inhibitions of terodiline and propiverine were significantly greater than those of oxybutynin and atropine. Each drug caused a concentration-dependent inhibition of the contraction induced by electrical field stimulation; the maximum inhibitions of terodiline and propiverine were significantly greater than those of oxybutynin and atropine. The results suggest that the drugs have both anticholinergic and calcium antagonistic effects. Furthermore, it also appears that part of the human bladder contraction, which was significantly inhibited by terodiline and propiverine, is an atropine-resistant component.",1995.0,0,0
281,8877354,Long-term bladder dysfunction in boys with posterior urethral valves.,C Pfister; L Wagner; J N Dacher; A Liard; B Boillot; P Mitrofanoff,"We report a series of 60 children operated on for posterior urethral valve (PUV) before the age of 5 years and followed up for 10 years. This work aims to study the vesico-sphincteric sequelae of this malformation. 38 patients showed early urinary incontinence post-operatively. Of them, 20 were re-evaluated 10 years later by pelvic ultrasonography, pressure flow studies combined with EMG and assessment of renal function. 8 patients refused to undergo these investigations and 10 were lost to follow-up. Of the 28 evaluable patients, 22 are currently continent and a complete urodynamic study was performed for the 6 (10%) incontinent patients. Of them, 3 showed uninhibited detrusor contractions. The vesical compliance was frequently within the normal limits. No case of detrusor-sphincteric dyssynergy or urethral hypotony was found. 2 were successfully treated by oxybutinin and biofeedback reeducation, 2 were partially improved but their prostates are still in growth and the possibility of implanting an artificial sphincter was discussed in the remaining 2. The urodynamic evaluation of those patients in the long-term is encouraging.",1996.0,0,0
282,8881937,Phytotherapy for the prostate.,A C Buck,,1996.0,0,0
283,8941431,Nonoperative management of urinary incontinence.,I E Nygaard,"Recent public health policies emphasize managing urinary incontinence nonoperatively, rather than proceeding directly to surgery. Advantages of this approach include decreased cost and risk. Additionally, incontinence treatment becomes accessible to many more women, by expanding care to nonspecialists. This article reviews data published in the past 18-24 months pertaining to conservative management of incontinence. Specific modalities reviewed include pelvic floor muscle exercises, electrical stimulation, medication, vaginal devices, and bladder training.",1996.0,0,0
284,8963976,Intravesical oxybutynin for spinal cord injury patients.,S M Szollar; S M Lee,"The treatment of choice for the failure to restore neurogenic bladder dysfunction, managed with clean intermittent catheterization program with incontinence, is anticholinergic medication. The goal is to increase bladder capacity, and decrease intravesical pressure in order to maintain continence between catheterizations. The most commonly used anticholinergic medication in the United States is Oxybutynin. Previous clinical studies have shown that 61% of the patients on oral Oxybutynin report adverse systemic side effects and are noncompliant in taking it. In 48% of the patients, possibly due to their noncompliance, oral Oxybutynin Hydrochloride is ineffective. In this study, 13 spinal cord injured patients with a failure to restore bladder dysfunction were treated with intravesical Oxybutynin. Nine patients improved on the regimen while one patient underwent surgical bladder augmentation. Postoperatively, this patient continued to be incontinent between catheterizations. Reinstitution of intravesical Oxybutynin stabilized the patient's bladder with clean intermittent catheterization without further intervention. After 3 months post instillation in the urodynamic studies, the mean bladder capacity increased, the mean volume at first contraction increased and the leak point pressure decreased. The decrease in leak point pressure was statistically significant. Leak point pressure is one of the most important parameters we monitor to preserve upper urinary tract function. We recommend the trial of intravesical Oxybutynin for patients who fit the criteria of the protocol prior to surgical bladder augmentation.",1996.0,0,0
285,8996386,The role of ureter in the creation of Mitrofanoff channels in children.,Y Mor; A M Kajbafzadeh; K German; P D Mouriquand; P G Duffy; P G Ransley,"Since 1980 numerous variations of the Mitrofanoff principle have been described. We report on 22 children in whom a ureteral Mitrofanoff channel was created. Between 1986 and 1995 a ureteral Mitrofanoff channel was constructed as a catheterizable conduit in 22 children 2 to 15 years old (average age 6.5) with various abnormalities of the lower urinary tract, mainly exstrophy and neurogenic bladder. Indications included unavailability or unsuitability of the appendix, preference for appendix as a catheterizable colonic stoma for antegrade washouts or concomitant removal of a nonfunctioning kidney, leaving the ureter available for use. Surgical technique was based on the principles of appendicovesicostomy and in 9 cases the ureteral Mitrofanoff channel was reimplanted. Followup ranged from 1 to 72 months (average 30.5). Complications included stenosis of the conduit that caused difficult catheterization in 3 patients, necessitating dilation or minor revision in 2 and complete replacement by appendix in 1. Urinary leakage from the Mitrofanoff channel in 5 patients was treated with polydimethylsiloxane injection or oxybutinin. In 1 patient the channel was reimplanted, since the catheter struck the bladder neck during catheterization and caused severe pain. Results of the ureteral Mitrofanoff channel seem somewhat less satisfactory than those of appendicovesicostomy but they remain acceptable and even comparable, strongly supporting its use in certain circumstances.",1997.0,0,0
286,9072550,"Comparison of oxybutynin and its active metabolite, N-desethyl-oxybutynin, in the human detrusor and parotid gland.",K Waldeck; B Larsson; K E Andersson,"To compare in vitro the antimuscarinic effect of oxybutynin and its active metabolite, N-desethyl-oxybutynin, on human detrusor, and their binding characteristics in detrusor and parotid gland. Antimuscarinic effect in the detrusor was assessed as the ability of the drugs to inhibit carbachol-induced contractions and contractions induced by electrical nerve stimulation. In addition, the drugs' ability to displace 3H-QNB from muscarinic receptors was investigated. Both oxybutynin and N-desethyl-oxybutynin caused a rightward shift of the concentration-response curve for carbachol without depression of the maximum, indicating a competitive antagonism. The pA2 values were 7.8 for oxybutynin and 7.6 for N-desethyl-oxybutynin. Contractions induced by electrical nerve stimulation were depressed by 87% by oxybutynin (10 microM) and by 91% by N-desethyl-oxybutynin (10 microM). In radioligand receptor binding studies on the detrusor, oxybutynin and N-desethyl-oxybutynin had uniform displacement curves and the same pKi value, 8.2. The affinity for N-desethyl-oxybutynin in the parotid gland was significantly higher, the pKi value being 8.7. The corresponding figure for oxybutynin was 8.5. We conclude that oxybutynin and N-desethyl-oxybutynin have a similar antimuscarinic effect in the human detrusor, and the same binding characteristics in detrusor and parotid gland, respectively.",1997.0,0,0
287,9105189,Role of pharmacotherapy for urinary incontinence.,B D Weiss,,1997.0,0,0
288,9121357,Tolterodine--a new bladder selective muscarinic receptor antagonist: preclinical pharmacological and clinical data.,L Nilvebrant; B Hallén; G Larsson,"Tolterodine is a new, potent and competitive muscarinic receptor antagonist in clinical development for the treatment of urge incontinence and other symptoms of unstable bladder. Tolterodine has a high affinity and specificity for muscarinic receptors in vitro and it exhibits a selectivity for the urinary bladder over salivary glands in vivo. A major active metabolite, (PNU-200577) the 5-hydroxymethyl derivative of tolterodine, has a similar pharmacological profile. Based on pharmacological and pharmacokinetic data, it has been concluded that this metabolite contributes significantly to the therapeutic effect of tolterodine. The bladder selectivity demonstrated by tolterodine and PNU-200577 in vivo cannot be attributed to selectivity for a single muscarinic receptor subtype. Moreover, this favourable tissue-selectivity seems to occur also in humans. Tolterodine is well tolerated and it exerts a marked effect on bladder function in healthy volunteers. Phase II data indicate that tolterodine is an efficacious and safe treatment for patients with idiopathic detrusor instability or detrusor hyperreflexia. An optimal efficacy/side-effect profile is obtained with tolterodine, at a dosage of 1 or 2 mg twice daily, which seems to have less propensity to cause dry mouth than the currently available antimuscarinic drugs.",1997.0,0,0
289,9144906,"Efficacy and safety of two doses of tolterodine versus placebo in patients with detrusor overactivity and symptoms of frequency, urge incontinence, and urgency: urodynamic evaluation. The International Study Group.",U Jonas; K Höfner; H Madersbacher; T H Holmdahl,"Tolterodine is a new competitive muscarinic receptor antagonist developed for the treatment of the unstable bladder. A total of 242 patients were enrolled in a multicenter, multinational, randomized, double-blind, placebo-controlled study conducted over a period of 4 weeks in patients with detrusor overactivity and symptoms of frequency, urgency, and urge incontinence. The objective of the study was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d. versus placebo. At week 4 a statistically significant increase in the volume at first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally well tolerated. The incidence of dry mouth, as the most commonly reported adverse event, was only 9% and of mild to moderate intensity.",1997.0,1,1
290,9181922,[Role of alfuzosin in the treatment of functional voiding disorders in women].,M D'Armiento; R Damiano; M De Sio; S Perdonà; C Santonastaso; D Mattace Raso,"Voiding dysfunction of the lower urinary tract represent a diagnostic and therapeutic challenge being the symptoms and urodynamic finding not strictly related. 34 women with urgency-frequency symptoms and post voiding residual urine were treated with alfuzosin 2.5 mg. twice daily alone or associated to oxibutinine 25 mg twice daily in patients with destrusor instability. After 30 days from therapy 69% presented a post void residual urine less than 40 ml, while 76% presented a flw max more than 15 ml/sec. At follow up 12 months the results remained unchanged. Alfuzosin alone or in association with oxibutinin can lower the urinary resistance to flow without modifying the maximum urethral pressure (MUP).",1997.0,0,0
291,9186365,Electromotive administration of oxybutynin into the human bladder wall.,S M Di Stasi; A Giannantoni; R Massoud; C Cortese; G Vespasiani; F Micali,"To compare concentrations of oxybutynin in the human bladder wall after either passive delivery (PD) or electromotive administration (EMDA). Tissue sections of human bladder were inserted into a diffusion cell with urothelium exposed to the donor compartment containing oxybutynin (4.5 mg. in 100 ml. NaCl 0.45%) and an anode. Twelve paired experiments, ""current 5 mA/no current"", were conducted over 15 minutes. Oxybutynin tissue contents were measured and tissue viability, morphology and oxybutynin stability were assessed. Mean oxybutynin tissue concentrations were 3.84 micrograms./gm. in samples exposed to EMDA and 0.87 microgram./gm. in samples exposed to PD (p = 0.0006). The mean coefficients of variation were 57.85% in EMDA experiments and 89.78% in PD experiments. Tissues were viable and undamaged histologically and no oxybutynin structural modification was observed. EMDA enhances oxybutynin administration into viable bladder wall and reduces the variability in drug delivery rate.",1997.0,0,0
292,9200560,Tolterodine--a new bladder-selective antimuscarinic agent.,L Nilvebrant; K E Andersson; P G Gillberg; M Stahl; B Sparf,"Tolterodine is a new muscarinic receptor antagonist intended for the treatment of urinary urge incontinence and other symptoms related to an overactive bladder. The aim of the present study was to compare the antimuscarinic properties of tolterodine with those of oxybutynin, in vitro and in vivo. Tolterodine effectively inhibited carbachol-induced contractions of isolated strips of urinary bladder from guinea pigs (K(B) 3.0 nM; pA2 8.6; Schild slope 0.97) and humans (K(B) 4.0 nM; pA2 8.4; Schild slope 1.04) in a concentration-dependent, competitive manner. The affinity of tolterodine was similar to that derived for oxybutynin (K(B) 4.4 nM; pA2 8.5; Schild slope 0.89) in the guinea-pig bladder. Tolterodine (21-2103 nmol/kg (0.01-1 mg/kg); intravenous infusion) was significantly more potent in inhibiting acetylcholine-induced urinary bladder contraction than electrically-induced salivation in the anaesthetised cat. In contrast, oxybutynin displayed the opposite tissue selectivity. Radioligand binding data showed that tolterodine bound with high affinity to muscarinic receptors in urinary bladder (K(i) 2.7 nM), heart (K(i) 1.6 nM), cerebral cortex (K(i) 0.75 nM) and parotid gland (K(i) 4.8 nM) from guinea pigs and in urinary bladder from humans (K(i) 3.3 nM). Tolterodine and oxybutynin were equipotent, except in the parotid gland, where oxybutynin bound with 8-times higher affinity (K(i) 0.62 nM). Binding data on human muscarinic m1-m5 receptors expressed in Chinese hamster ovary cells showed that oxybutynin, in contrast to tolterodine, exhibits selectivity (10-fold) for muscarinic m3 over m2 receptors. The K(B) value determined for oxybutynin (4.4 nM) in functional studies on guinea-pig bladder correlated better with the binding affinity at muscarinic M2/m2 receptors (K(i) 2.8 and 6.7 nM) than at muscarinic M3/m3 receptors (K(i) 0.62 and 0.67 nM). The tissue selectivity demonstrated for tolterodine in vivo cannot be attributed to selectivity for a single muscarinic receptor subtype. However, the combined in vitro and in vivo data on tolterodine and oxybutynin may indicate either that muscarinic M3/m3 receptors in glands are more sensitive to blockade than those in bladder smooth muscle, or that muscarinic M2/m2 receptors contribute to bladder contraction.",1997.0,0,0
293,9202559,Oxybutynin in the treatment of early detrusor instability after transurethral resection of the prostate.,C E Iselin; F Schmidlin; F Borst; S Rohner; P Graber,"To evaluate the symptomatic and urodynamic effects of oxybutynin in the control of irritative micturitional symptoms during the first week after transurethral resection of benign prostatic hyperplasia (BPH). Fifty-three patients (median age 67 years, interquartile range 62-72) were included prospectively in a double-blind placebo-controlled study. Pre-operatively, uroflowmetry and cystometrography (CMG) were performed, and the post-void residual volume (PVR) measured; symptoms were rated according to the Boyarski score. CMG was repeated on the first post-operative day and medication was started on the third day. Before withdrawing the catheter on the fifth day. CMG was repeated. Three days later, symptoms were evaluated according to the Boyarski score and uroflowmetry and the estimate of PVR reassessed. In comparison with placebo, oxybutynin significantly decreased frequency, urgency and detrusor pressure at first sensation of filling. However, oxybutynin did not lower the rate of pre-operative detrusor instability and exerted no effect on the maximal capacity of the bladder and corresponding detrusor pressure. Dryness of mouth was reported in 13% and 65% of patients receiving placebo and oxybutynin, respectively. Oxybutynin alleviates early irritative symptoms after transurethral resection of BPH, without consistently modifying bladder urodynamics.",1997.0,0,0
294,9236554,Explicit criteria for determining potentially inappropriate medication use by the elderly. An update.,M H Beers,"This study updates and expands explicit criteria defining potentially inappropriate medication use by the elderly. Additional goals were to address whether adverse outcomes were likely to be clinically severe and to incorporate clinical information on diagnoses when available. These criteria are meant to serve epidemiological studies, drug utilization review systems, health care providers, and educational efforts. Consensus from a panel of 6 nationally recognized experts on the appropriate use of medication in the elderly was sought. The expert panel agreed on the validity of 28 criteria describing the potentially inappropriate use of medication by general populations of the elderly as well as 35 criteria defining potentially inappropriate medication use in older persons known to have any of 15 common medical conditions. Updated, expanded, and more generally applicable criteria are now available to help identify inappropriate use of medications in elderly populations. These criteria define medications that should generally be avoided in the ambulatory elderly, doses or frequencies of administrations that should generally not be exceeded, and medications that should be avoided in older persons known to have any of several common conditions.",1997.0,0,0
295,9258982,,,,,0,1
296,9272412,Itraconazole moderately increases serum concentrations of oxybutynin but does not affect those of the active metabolite.,E Lukkari; A Juhakoski; K Aranko; P J Neuvonen,"Oxybutynin has low oral bioavailability due to an extensive presystemic metabolism. It has been suggested that the biotransformation of oxybutynin is dependent on CYP3A. Because itraconazole, a widely used mycotic, is a potent inhibitor of CYP3A4, we wanted to study a possible interaction between oxybutynin and itraconazole. In this double-blind, randomized, two-phase cross-over study, ten healthy volunteers received either 200 mg itraconazole or placebo for 4 days. On day 4, each volunteer ingested a single dose of 5 mg oxybutynin. Serum concentrations of oxybutynin, its active metabolite N-desethyloxybutynin, and itraconazole were monitored over 24 h. Itraconazole significantly increased both the area under the serum drug concentration-time curve (AUC0-t) and the peak concentration of oxybutynin twofold. The AUC0-t and the peak concentration of N-desethyloxybutynin were not significantly affected by itraconazole. Itraconazole did not change the peak time or the elimination half-life of either oxybutynin or N-desethyloxybutynin. The occurrence of adverse events after oxybutynin administration was not increased by itraconazole. Itraconazole moderately increases serum concentrations of oxybutynin, probably by inhibiting the CYP3A-mediated metabolism. However, the concentrations of N-desethyloxybutynin were practically unchanged. Since about 90% of the antimuscarinic activity of oxybutynin is attributable to N-desethyloxybutynin, any interaction of oxybutynin with CYP3A4 inhibiting drugs has only minor clinical significance.",1997.0,0,1
297,9313659,The use of salivary stimulant pastilles to improve compliance in women taking oxybutynin hydrochloride for detrusor instability: a pilot study.,P Hooper; D G Tincello; D H Richmond,"To assess the efficacy of salivary stimulant pastilles in improving tolerance of and compliance with oxybutynin chloride for detrusor instability. Thirty women with detrusor instability were treated with oxybutynin in either a fixed or variable dose. After 3 weeks, patients were given salivary stimulant pastilles (Salivix, Thames Laboratories, Clwyd, UK) to chew as often as required. Symptom diaries were used to record episodes of dry mouth (xerostomia) together with a 100 mm visual analogue scale (VAS) score of the severity of xerostomia. The frequency of xerostomia was unchanged but there was a significant decrease in median severity from 71 to 39 on the VAS (P < 0.05, Mann-Whitney U-test). Nine patients on the variable-dose regimen tolerated a higher dose of oxybutynin when taking the pastilles (P < 0.01, Wilcoxon's matched-pairs test). Salivary stimulant pastilles appear to be a useful adjuvant therapy for patients receiving oxybutynin chloride for detrusor instability, allowing higher doses of oxybutynin to be tolerated.",1997.0,0,1
298,9351481,"Medically recognized urinary incontinence and risks of hospitalization, nursing home admission and mortality.",D H Thom; M N Haan; S K Van Den Eeden,"this study examined the association between medically recognized urinary incontinence and risk of several disease conditions, hospitalization, nursing home admission and mortality. review and abstraction of medical records and computerized data bases from 5986 members, aged 65 years and older, of a large health maintenance organization in northern California. there was an increased risk of newly recognized urinary incontinence following a diagnosis of Parkinson's disease, dementia, stroke, depression and congestive heart failure in both men and women, after adjustment for age and cohort. The risk of hospitalization was 30% higher in women following the diagnosis of incontinence [relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.2-1.5] and 50% higher in men (RR = 1.5, 95% CI = 1.3-1.6) after adjustment for age, cohort and co-morbid conditions. The adjusted risk of admission to a nursing facility was 2.0 times greater for incontinent women (95% CI = 1.7-2.4) and 3.2 times greater for incontinent men (95% CI = 2.7-3.8). In contrast, the adjusted risk of mortality was only slightly greater for women (RR = 1.1; 95% CI = 0.99-1.3) and men (RR= 1.2; 95% CI= 1.1-1.4). urinary incontinence increases the risk of hospitalization and substantially increases the risk of admission to a nursing home, independently of age, gender and the presence of other disease conditions, but has little effect on total mortality.",1997.0,0,0
299,9366317,The role of oxybutynin in spinal cord injured patients with indwelling catheters.,Y H Kim; E T Bird; M Priebe; T B Boone,"The long-term benefits of oral oxybutynin in spinal cord injured patients with indwelling catheters is unknown. We reviewed our experience with this population of men and present the results of our analysis. A total of 109 male spinal cord injured patients at the Houston Veterans Affairs Medical Center have been treated with chronic indwelling catheters (80 transurethral and 29 suprapubic). Thirty-eight patients (35%) were identified as using oxybutynin on a regular basis. These patients were compared to those not using oxybutynin with regard to urodynamic parameters and upper tract deterioration. Specifically examined were bladder compliance, bladder leak point pressure, vesicoureteral reflux, hydronephrosis, urolithiasis, febrile urinary tract infections and serum creatinine greater than 2 mg./dl. The mean duration of indwelling catheter use was 11.9 years (12.4 without oxybutynin and 10.9 on oral oxybutynin). Of the 31 patients with normal compliance (greater than 20 ml./cm. water), 24 (77%) were using oxybutynin (p = 0.001). Bladder leak point pressures were abnormal (greater than 35 cm. water) in 5 of 32 patients (16%) on oxybutynin versus 34 of 60 (57%) without it (p <0.001). Hydronephrosis was present in 15 of 66 patients (23%) without oxybutynin versus 1 of 36 (3%) with oxybutynin (p = 0.009). Febrile urinary tract infections occurred in 4 of 35 patients (11%) versus 17 of 62 patients (27%) with or without oxybutynin, respectively (p = 0.077). No significant differences were found between the 2 groups with regard to reflux, renal scars, stones or elevated serum creatinine. It appears that regular use of oxybutynin may be beneficial in spinal cord injured patients who require chronic indwelling catheters for bladder management. Our analysis reveals that patients who take oxybutynin regularly have better bladder compliance, lower bladder leak point pressures and less hydronephrosis. Until a prospective, randomized trial reveals contradicting outcomes, empiric use of oxybutynin in all spinal cord injured patients requiring chronic indwelling catheters seems justified.",1997.0,0,0
300,9404562,Serum tryptase levels in adverse drug reactions.,E Ordoqui; J M Zubeldia; A Aranzábal; M Rubio; T Herrero; P Tornero; V M Rodríguez; A Prieto; M L Baeza,"We evaluated the usefulness of individual tryptase levels and variations after adverse drug reactions in 64 patients. Our aim was to find a tool for the diagnosis of drug allergy. Thirty-seven subjects were confirmed to have drug allergy, 12 had nonsteroidal anti-inflammatory drug (NSAID) reactions, five had negative controlled drug challenges (NAAR), and 10 had symptoms after placebo intake (PLA). Serum tryptase levels greatly increased after anaphylactic shocks (2242%) and anaphylaxis (710.5%). Patients with allergic urticaria and those with idiosyncratic responses to acetylsalicylic acid (ASA) exhibited a small increase in serum tryptase (49.5% and 38.2%, respectively). In the other two groups (NAAR and PLA), no variation in this serum protease was observed. The time of appearance of the serum tryptase peak differed considerably among patients with similar clinical reactions (from 30 min to 6 h) and was independent of the latent period, severity of symptoms, or the amount of tryptase released. We conclude that serum tryptase determinations are helpful in the diagnosis of anaphylactic shock and anaphylaxis, but serial measurements may be needed to confirm mast-cell participation in milder reactions.",1997.0,0,0
301,9412364,[Medical treatment of bladder instability. Our experience].,C Zubiaur Líbano; A Loizaga Iriarte; V Ullate Jaime; E García Sastre; J M Arciniega García; R Infante Riaño; N Flores Corral,"To identify the factors that influence response to treatment of vesical instability. A retrospective study was conducted to assess the efficacy of drug therapy with oxybutinin and imipramine in 89 patients with urodynamically demonstrated detrusor hyperreactivity. Control evaluations were performed at 2, 5 and 8 months. Evaluation of the results took into account the etiology, pressure and volume at which the wave of instability appeared. The results were evaluated according to patient subjective criteria. We observed a positive response (cure and improvement) to treatment with oxybutinin alone or oxybutinin+imipramine in 66.25% of the cases; side effects were observed in 44%. There was a 20% improvement in the positive response rate when the wave intensity was greater than 55 cm H2O and the bladder volume at which this occurred was greater than 150 ml. No patient treated with second line drug therapy (flavoxate, nifedipine and trospium chloride) cured. The etiology of vesical instability did not influence response to therapy. Waves with a greater intensity and those that appeared at higher volumes responded better to treatment. Nearly half of the patients with side effects required a reduction of the dosage or withdrawal of the drug. Our results and those reported elsewhere indicate that non-responders to treatment with oxybutinin alone or in combination with imipramine are unlikely to improve with currently available drug therapy.",1997.0,0,0
302,9426760,Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis.,R A Appell,"To examine the safety, efficacy, and tolerability of tolterodine in four randomized, double-blind, parallel, multicenter, 12-week studies of patients with overactive bladder. Two of the four studies compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily) and placebo, one study compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily), and one study compared two dosages of tolterodine (1 and 2 mg twice daily) to placebo. Efficacy was determined from micturition diaries and patient perception of their bladder condition. Safety and tolerability were assessed from adverse events and laboratory measures. A total of 1,120 patients were randomized and treated at 134 centers. For the primary efficacy variable, the number of micturitions/24 hours, pooled results showed a significant decrease from baseline for the 1 mg tolterodine (P < 0.001), 2 mg tolterodine (P < 0.001), and 5 mg oxybutynin (P < 0.01) groups, compared to placebo. Both tolterodine doses and oxybutynin significantly decreased incontinence episodes/24 hours and significantly increased volume voided/micturition, compared to placebo. Tolterodine at a dose of 2 mg twice daily and 5 mg oxybutynin twice daily were significantly more effective in improving patient perception of bladder condition than placebo. Tolterodine at a dose of 2 mg and 5 mg oxybutynin were equivalent in their effectiveness. Tolterodine at doses of 1 mg and 2 mg were tolerated significantly better than oxybutynin when adverse events, dry mouth (both frequency and intensity), dose reductions, and patient withdrawals were considered. Although oxybutynin is highly effective, its clinical utility is limited by systemic side effects that lead to frequent discontinuation of treatment or dose reductions. Patients receiving tolterodine should not experience these limitations and instead will get safe and long-term effective treatment for their condition.",1998.0,0,0
303,9434659,Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride.,I R Katz; L P Sands; W Bilker; S DiFilippo; A Boyce; K D'Angelo,"To evaluate the cognitive effects of acute challenges with the antispasmodic agent oxybutynin hydrochloride in normal older volunteers and to compare these effects with those attributable to diphenhydramine, another commonly used medication with anticholinergic (muscarinic-blocking) activity. A double-blind, placebo-controlled cross-over study. Laboratory evaluations of community subjects. A convenience sample of 12 volunteers, average age 69.17 years. Baseline assessment was followed by randomized administration of a placebo, oxybutynin hydrochloride (5 and 10 mg), and diphenhydramine hydrochloride (50 mg) in test sessions separated by 1 week. Evaluation of cognitive performance with a 1-hour battery of pencil and paper, interviewer-administered, and computer-administered tests beginning 90 minutes after drug (or placebo) administration. Random regression analyses demonstrated that oxybutynin caused significant cognitive decrements on seven of 15 cognitive measures, and diphenhydramine caused decrements on five measures. The most sensitive measures for detecting the effects of oxybutynin hydrochloride were the Buschke Selective Reminding Test and Reaction Time. These findings demonstrate that oxybutynin can cause cognitive impairment and suggest that physicians prescribing it should monitor their patients to facilitate the early recognition of those who experience drug-related cognitive deficits. More generally, the findings demonstrate that systematic research with normal volunteers can identify cognitive toxicity not recognized during the process of drug development or postmarketing surveillance.",1998.0,1,1
304,9467475,Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study.,L Rentzhog; S L Stanton; L Cardozo; E Nelson; M Fall; P Abrams,"To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence). A double-blind, placebo-controlled, multicentre study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks' treatment. A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of < or = 2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1-2 mg twice daily.",1998.0,1,1
305,9493232,[An update on clinical and therapeutic aspects of nocturnal enuresis].,M L Chiozza,"Justification of early treatment of nocturnal enuresis is founded in the negative psychological impact on the child. In fact nocturnal enuresis delays early autonomy and socialisation by decreasing in self-esteem and self-confidence. Nocturnal enuresis classification is the preliminary step to correct therapy. Enuresis must be classified as primary (never acquired nocturnal control) or secondary (at least 6 months of dry nights). A child is also classified as having monosymptomatic enuresis if she/he experienced only night wetting and symptomatic enuresis if she/he experienced night wetting associated with diurnal voiding symptoms (urinated > or = 7 times a day, urgency, damp pants, squatting, holding the perineum, sitting on one heel). Monosymptomatic patients must be treated with desmopressin nasal spray at the daily dose of 20 micrograms at bed time. If the reduction of at least the 50% of the basal number of the wet nights is not achieved, the dosage must be increased until 40 micrograms. For patients affected by rhinitis or asthma, desmopressin is now available in tablets. In symptomatic patients desmopressin therapy must be associated to oxybutinin (5 mg x 2). Therapy interruption must be gradual with desmopressin reduction of 10 micrograms every 30 days. In symptomatic patients oxybutinin must be introduced only at bed time. The efficacy of the drugs depends on the therapy length. The highest percentage of success is obtained if the treatment is protracted for at least six months. Antidepressants are also used for nocturnal enuresis especially imipramine. The dosage varies between 0.5-1.5 mg/ kg/daily. As plasmatic levels are achieved only in 30% of treated patients, a 3-5 fold increase in suggested. Nevertheless these levels result in near toxic threshold concentration. Sporadic treatment purposes include amytriptiline, diclofenac sodicum, viloxsazine and methilphenidate if giggle incontinence is present. Non responders may be treated with alarm. If after 16 weeks of treatment no success is obtained alarm use must be interrupted.",1998.0,0,0
306,9495736,Pharmacologic options for the overactive bladder.,A J Wein,"To review the current pharmacologic options for treatment of the overactive bladder and to describe potential therapies on the horizon. The literature on the clinical efficacy and safety of the currently available agents is described. According to the guidelines issued by the Agency for Health Care Policy and Research (AHCPR), anticholinergic agents should be the first-line pharmacologic therapy for patients with detrusor instability. Oxybutynin is the anticholinergic of choice for this indication, whereas propantheline is the second-line therapy. Although calcium antagonists have been investigated, the one such drug introduced for the treatment of overactive bladder (terodiline) was withdrawn from the market because of a risk of cardiac arrhythmia. Studies of potassium channel openers have found either a lack of clinical efficacy or an unacceptable level of side effects. Alpha-adrenergic antagonists may be useful for decreasing bladder overactivity in patients who have autonomous bladders as the result of conditions such as spinal cord injury. Tricyclic antidepressants (particularly imipramine) may be effective in decreasing bladder contractility, although the AHCPR guidelines caution that these drugs should be reserved for use in carefully evaluated patients. Future developments in the treatment of detrusor overactivity are likely to occur in 3 categories: drugs that affect peripheral excitatory mechanisms, drugs that inhibit afferent mechanisms, and drugs that affect more central actions at either the ganglionic, spinal cord, or supraspinal level. Although pharmacologic management of the overactive bladder has progressed little in the past 10 years, the future may hold the promise of more effective therapies.",1998.0,0,0
307,9499276,[Efficacy of oxybutynin chloride in children with vesico-ureteral reflux and detrusor instability].,J E Batista Miranda; P Arañó Bertran; J Caffaratti; R Regalado Pareja; J M Garat Barredo; C Errando Smet; J Vicente Rodríguez,"The purpose of this study was to assess the urodynamic (UD), radiological (VCUG) and clinical outcome in patients with detrusor instability (DI) and vesico-ureteral reflux (VUR). UD and VCUG findings in 24 patients between 4 and 18 years of age (mean 7.6 years) with a simultaneous diagnosis of VUR and DI were reviewed. All presented with recurrent urinary tract infections (UTI). Twenty were female of whom 8 also had enuresis and daytime symptoms. Ten had bilateral VUR, making a total of 34 units. Mean follow-up was 40 months (range 18-97 months) and at least 2 UD studies were done. Treatment consisted of oxybutinin chloride (OC) and chemoprophylaxis. Treatment lasted an average of 31 months with an average dose of 11 mg/day. There was a statistically significant improvement in UTI rate, enuresis score and UD parameters [CysCap, volume at 1st contraction, maximum contraction and compliance (comp)]. Thirteen patients achieved stable bladders and 9 had some UD improvement (3 with low compliance and 2 with less severe DI), leaving 2 with unchanged DI. Reflux disappeared in 20 units and was downgraded in 6. VUR improvement coincided with the cases of UD improvement. Persistence of DI was always associated with persistent VUR. Oxybutinin treatment can be long, but UD and VUR improvement run parallel in most cases. The rare discrepant cases point towards a multifactorial ethology in this condition.",1998.0,0,0
308,9510336,Economic costs of urinary incontinence in 1995.,T H Wagner; T W Hu,"Urinary incontinence imposes a significant financial burden on individuals, their families, and healthcare organizations. For individuals 65 years of age and older these costs are substantial, increasing from $8.2 billion (1984 dollars) to $16.4 billion (1993 dollars). Both of these cost-of-illness estimates, however, relied on data and factors that have changed over time. This study updates these cost estimates. The 1995 societal cost of incontinence for individuals aged 65 years and older was $26.3 billion, or $3565 per individual with urinary incontinence. Limitations, implications, and directions for future research are also discussed.",1998.0,0,0
309,9516036,The pharmacokinetics of oxybutynin is unaffected by gender and contraceptive steroids.,E Lukkari; T Hakonen; P J Neuvonen,"The effect of gender and concomitant use of contraceptive steroids on the absorption and metabolism of oxybutynin was investigated in 49 healthy volunteers, 24 females and 25 males. Serum concentrations of oxybutynin and its active metabolite, N-desethyloxybutynin, were measured for up to 48 h after ingestion of a single dose of 10 mg oxybutynin. Intake of oral contraceptive steroids had no significant effect on the pharmacokinetic parameters of oxybutynin or its metabolite. Both in males and females, the mean area under the curve (AUC0-t) of N-desethyloxybutynin was about 13 times higher and the peak concentration (Cmax) 15 to 19 times higher than the AUC0-t and Cmax of the parent oxybutynin, with no significant differences between males and females. The pharmacokinetics of orally administered oxybutynin shows a considerable interindividual variability, but is unaffected by gender and use of contraceptive steroids.",1998.0,1,1
310,9586268,[Management of hyposalivation caused by oxybutynin chloride in the treatment of the unstable bladder].,O Arango Toro; G Nohales Taurines; R Cortadellas Angel; R Castro Santamaría; A Gelabert Mas,"To know the incidence of adverse reactions from Oxybutynin Chloride, with special reference to salivary hyposecretion and to evaluate the effectiveness of the different alternatives employed to solve it. 144 adult patients with signs and symptoms of voiding urgency and detrusor-hyperactivity incontinence, who were treated with Oxybutynin 5 to 15 mg/day. Hyposecretion of several exocrine glands was evaluated using a questionnaire that included subjective and objective parameters. For managing purposes, patients were divided into 3 groups: 1) General measures; 2) Therapy with sialagogues; and 3) Replacement therapy with artificial saliva. 42% patients treated with Oxybutynin developed mild-to-moderate hyposialism. 26% had severe hyposialism, always related to high dose Oxybutynin. 6% skin dryness, 3% eye dryness and 2% dryness in all the above glands (dry syndrome). Regarding treatment, most patients with mild-to-moderate hyposialism were managed with simple general measures. In severe hyposialism, both sialagogues (Eledoisine) and artificial saliva (Bucalsone) were resolutive in over 90% cases. Oxybutynin is an effective drug to stop detrusor hyperactivity, but it has a high rate of anticholinergic adverse reactions. There is a number of effective therapeutic options available to alleviate these effects, which allow the patient to continue with the treatment.",1998.0,0,0
311,9599741,Effects of systematic treatment based on overnight simultaneous monitoring of electroencephalography and cystometry.,A Kawauchi; N Imada; Y Tanaka; Y Yamao; H Watanabe,"To clarify the effects of systematic treatment based on overnight simultaneous monitoring by electroencephalography (EEG) and cystometry (CM) on each type of enuresis. For enuresis type I, the change in the awakening response during the conditioning treatment with a therapeutic machine was observed. For enuresis type IIa, the effect of imipramine on the EEG was observed. For enuresis type IIb, the effect of oxybutynin hydrochloride on the cystometrogram (CMG) was observed. Values, in which the awakening score on the second night was subtracted from the score on the last night, were significantly higher in the effective cases than in the unchanged cases. Out of the 3 patients in whom imipramine was effective, an awakening response on the EEG was observed in 2. Neither of the 2 unchanged cases showed an awakening response. Out of 4 patients in whom oxybutynin hydrochloride was effective, uninhibited contractions (UIC) on the CMG disappeared in 3. UIC stopped in neither of the 2 unchanged cases. Improvement of the awakening response plays an important role in the effectiveness of conditioning treatment with our therapeutic machine. The generation of awakening response is thought to be the most important result of imipramine directly concerned with its clinical effect on enuresis type IIa. The main result with oxybutynin hydrochloride in enuresis type IIb is thought to be related to its antispasmodic effect.",2000.0,0,0
312,9617596,Tolterodine.,C J Hills; S A Winter; J A Balfour,"Tolterodine is a competitive muscarinic receptor antagonist which has recently been launched for the treatment of overactive bladder. Tolterodine shows functional selectivity for the bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity. It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use. In patients with overactive bladder, toleterodine significantly reduces the frequency of micturition and number of incontinence episodes, while increasing the average volume voided. The onset of pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is maintained during long term treatment. In comparative trials, tolterodine and oxybutynin are equivalent in terms of efficacy. However, tolterodine is significantly better tolerated than oxybutynin, particularly with respect to the incidence and severity of dry mouth. No clinically relevant ECG changes have been noted with tolterodine.",1998.0,0,0
313,9624560,"Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle.",H Kikukawa; M Yoshida; Y Wada; K Nishi; S Ueda,"Temiverine (p-INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC-36, on isolated human bladder. Effects of temiverine and RCC-36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric field stimulation were evaluated using the muscle-bath technique, and compared with the effects of atropine and oxybutynin. Atropine (10(-9) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of the concentration-response curves to acetylcholine stimulation. The rank order of pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)-induced contractile responses. Rank order of maximum inhibition was RCC-36 = temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent inhibition of electric field-induced contraction with or without 10(-6) mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were significantly greater than that of oxybutynin. Atropine, oxybutynin, temiverine, and RCC-36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the atropine-resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.",1998.0,0,0
314,9638316,,,,,0,0
315,9655671,Toxicology reviews: physostigmine.,M Shannon,,1998.0,0,0
316,9656557,"[Which treatment should children with recurrent urinary infections, without anatomical anomalies, receive?].",E A Granados,"To determine the best treatment for children with recurrent infection of the lower urinary tract and without anatomical abnormalities. A clinical study was conducted on 150 children (30 boys and 120 girls), aged 4 to 36 months (mean 16), with recurrent urinary tract infections (UTI) and no radiological evidence of anatomical abnormalities. They were divided into three groups: group I was treated with a single nightly prophylactic dose of an antibiotic; group II received a single nightly dose of oxybutinin, or divided in 2-4 doses; group III received a single nightly prophylactic dose of an antibiotic and oxybutinin as in group II. There were more episodes of UTI in group I (44/50), more hospitalizations and problems of malnutrition, and a longer period of treatment was required. In group II, 14/50 children had episodes of UTI, their nutritional status improved and there were less hospitalizations. In group III, 3/50 children had episodes of UTI; they were the best responders and required a shorter duration of treatment. Prophylactic therapy requires a longer period of treatment. The use of oxybutinin is an alternative modality in the treatment of these children. Combination therapy with a single nightly dose of an antibiotic and anticholinergic (oxybutinin) appears to be the best therapeutic modality for children with recurrent UTI and no anatomical abnormality.",1998.0,0,0
317,9666761,"Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.",P Abrams; R Freeman; C Anderström; A Mattiasson,"To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition. After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily. Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.",1998.0,1,1
318,9671109,Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists.,P G Gillberg; S Sundquist; L Nilvebrant,"Tolterodine [(R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine ] is a new potent and competitive muscarinic receptor antagonist developed for the treatment of urinary urge incontinence and other symptoms of overactive bladder. In vivo, tolterodine exhibits functional selectivity for the urinary bladder over salivary glands, a profile that cannot be explained in terms of selectivity for a single muscarinic receptor subtype. The aim of this study was to compare the in vitro and in vivo antimuscarinic profiles of tolterodine with those of muscarinic receptor antagonists with distinct receptor subtype-selectivity profiles: darifenacin [(S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl]-2,2-d iphenylacetamide; selective for muscarinic M3 receptors]; UH-AH 37 (6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidinyl)acetyl]-11H-dibenzo-[b ,e][1,4]diazepine-11-one; low affinity for muscarinic M2 receptors); and AQ-RA 741 (11-([4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-py rido[2,3-b][1,4]benzodiazepine-6-one; high affinity for muscarinic M2 receptors). The in vitro profiles of these compounds were in agreement with previous reports; darifenacin and UH-AH 37 demonstrated selectivity for muscarinic M3/m3 over M2/m2 receptors, while the converse was observed for AQ-RA 741. In vivo, AQ-RA 741 was more potent (1.4-2.7-fold) in inhibiting urinary bladder contraction than salivation in the anaesthetised cat (i.e., a profile similar to that of tolterodine [2.5-3.3-fold]), while darifenacin and UH-AH 37 showed the reverse selectivity profile (0.6-0.8 and 0.4-0.5-fold, respectively). The results confirm that it is possible to separate the antimuscarinic effects on urinary bladder and salivary glands in vivo. The data on UH-AH 37 and darifenacin support the view that a selectivity for muscarinic M3/m3 over M2/m2 receptors may result in a more pronounced effect on salivation than on bladder contraction. The data on AQ-RA 741 may indicate that muscarinic M2/m2 receptors may have a role in bladder contraction.",1998.0,0,0
319,9693251,Follow-up of long-time treatment with intravesical oxybutynin for neurogenic bladder in children.,P Amark; G Bussman; S Eksborg,"Anticholinergic treatment for the hyperreflexic neurogenic bladder in childhood is an established method, together with clean intermittent catheterization (CIC), to promote continence and protect the upper urinary tract from deterioration. Recently, the use of oxybutynin, a compound with anticholinergic, smooth muscle relaxant and local anesthetic effects, has become widely used with both oral and intravesical administration. In this study we report 39 children with myelodysplasia, neurogenic bladder disturbance with detrusor hyperreflexia and/or high bladder pressure treated with CIC to which intravesical oxybutynin 0.1 mg/kg twice daily was added and administered as a sterile pharmacy-produced solution. The follow-up period was 0.66-5 years (mean 2.25). Continence was clearly promoted and urodynamic parameters improved whereas an increased occurrence of asymptomatic bacteriuria and lower urinary tract infections was noted. Compliance was good, adverse reactions rare, and in some cases vesicoureteral reflux (VUR) resolved. Also infants and very young children were treated without complications. Intravesical oxybutynin is effective to diminish bladder pathophysiology and promote continence in this patient group and is also well tolerated. Attention should be paid to the occurrence of urinary tract infections and VUR may resolve.",2000.0,0,0
320,9704249,Comparative tolerability of drug therapies used to treat incontinence and enuresis.,R G Owens; M M Karram,"Drug therapy for incontinence and enuresis has met with varying degrees of success. Currently, there is no medication available that specifically targets the lower urinary tract without having untoward effects elsewhere in the body. Patients with urge incontinence are the most difficult group to treat. The agents most commonly used to treat urge incontinence, i.e. anticholinergics, musculotropics and tricyclic antidepressants, are limited in their effectiveness and have anticholinergic adverse effects. Other medications with theoretical treatment potential such as nonsteroidal anti-inflammatory drugs and calcium antagonists require more in depth clinical study before widespread use is appropriate. Although estrogen is well tolerated, its role in the treatment of incontinence in postmenopausal women may be limited. Medical treatment for stress incontinence is most successful in patients with a mild condition. Drugs with alpha-adrenergic activity alone or in combination with estrogen in postmenopausal women, are fairly effective and demonstrate few adverse effects at doses used to treat stress incontinence. Enuresis pharmacotherapy consists mainly of desmopressin and tricyclic antidepressants. Adverse effects are minimal with the doses commonly used. While the majority of patients improve with therapy, a significant portion relapse after treatment is terminated. Tolerability of a particular therapy depends on the effectiveness and adverse effects of the agent, the severity of incontinence and the general health of the patient. In general, patients are willing to accept a greater degree of inconvenience if a drug produces the desired effect. However, individualisation of therapy should be used to maximise compliance and outcome. Blinded, dose-titration studies are needed to better determine doses for optimum tolerability. Research into drugs specifically targeting the lower urinary tract may lead to more effective and well tolerated therapy for incontinence and enuresis.",1998.0,0,1
321,9748713,Comparison of the effects of various spasmolytic drugs on isolated human and porcine detrusor smooth muscle.,S Uckert; C G Stief; K P Odenthal; A J Becker; M C Truss; U Jonas,"The spasmolytic activity of flavoxate (CAS 15301-69-6), anticholinergic agents oxybutynin (CAS 5633-20-5), and trospium chloride (CAS 10405-02-4), drugs commonly utilized in the therapy of hyperactive bladder, and phosphodiesterase (PDE) inhibitors papaverine (CAS 58-74-2) and vinpocetine (CAS 42971-09-5) on muscarinic contractions of detrusor smooth muscle strips isolated from human and porcine urinary bladder was studied in vitro using the organ bath technique. Trospium chloride was most effective in relaxing contractions elicited by muscarinic stimulation, while flavoxate was significantly less effective than all other drugs tested. The relaxing potency of oxybutynin was greater than those of PDE-inhibitors papaverine and vinpocetine but 3,000 fold less significant than those of trospium chloride. The effects of the individual drugs on muscarinic tension of both human and porcine detrusor muscle strips were nearly equal. The present results suggest that the pig might be an appropriate animal model for the study of effects of spasmolytic substances on the contractility of urinary bladder smooth muscle in vitro.",1998.0,0,0
322,9758325,Seizures in patients receiving concomitant antimuscarinics and acetylcholinesterase inhibitor.,L T Piecoro; D P Wermeling; F A Schmitt; J W Ashford,"Seizures occurred in two patients with probable Alzheimer's disease who were receiving long-term treatment with metrifonate, an irreversible acetylcholinesterase inhibitor. In both patients seizures were associated with discontinuation of short-term agents with high antimuscarinic properties. Hence, abrupt discontinuation of antimuscarinics or anticholinergics with high antimuscarinic properties in patients receiving long-term acetylcholinesterase inhibition therapy may be associated with a reduction of seizure threshold. With increasing administration of acetylcholinesterase inhibitors for patients with Alzheimer's disease, practitioners should be aware of the potential for drug-drug interactions and other complications. In general, it is good medical practice to avoid concomitant administration with centrally acting anticholinergic agents.",1998.0,0,0
323,9777178,P300 delay and attenuation in schizophrenia: reversal by neuroleptic medication.,K L Coburn; S D Shillcutt; K A Tucker; K M Estes; F B Brin; P Merai; N C Moore,"P300 amplitude reduction in schizophrenia has been found by many investigators, but P300 latency generally has been reported to be normal; however, conflicting findings are present in the literature, and interpretation has been confounded by medication effects and methodological differences. This study used a standard auditory oddball paradigm to compare the latency, amplitude, and topographic distribution of P300s in neuroleptic-free schizophrenic patients with those of healthy controls. The patients then were treated for 6 weeks with either remoxipride or haloperidol, and their P300s were reassessed. P300s were attenuated and delayed among neuroleptic-free patients. There was no evidence of peak lateralization or amplitude asymmetry over temporal areas. Subsequent neuroleptic medication normalized P300 latencies and increased P300 amplitudes, but the latter remained below normal limits over all except frontal areas. There were no correlations between P300 latency or amplitude and clinical symptomatology either before or after treatment. The finding of a P300 delay in neuroleptic-free schizophrenics that is normalized by neuroleptic medication has not been reported previously. Neuroleptic effects on P300 amplitude and latency appear to be independent of effects on clinical symptoms, and cannot be attributed to anticholinergic activity.",1998.0,0,0
324,9798802,"Effects of two anticholinergic drugs, trospium chloride and biperiden, on motility and evoked potentials of the oesophagus.",C Pehl; B Wendl; H Kaess; A Pfeiffer,"Anticholinergic drugs are known to impair the motor function of the oesophagus but their effects on the oesophageal afferent pathways are unknown. To determine the effects of a peripherally-acting (trospium chloride) and a centrally-acting (biperiden) anticholinergic drug on the motility and the evoked potentials of the oesophagus. Nine healthy volunteers were randomized to receive 1.2 mg trospium chloride (TC), 5 mg biperiden (BIP) or saline i.v. Primary peristalsis was elicited by swallowing a 5 mL water bolus and secondary peristalsis by insufflation of 20 mL air, 10 times each. Oesophageal potentials were evoked by electrical stimulation in the distal and proximal oesophagus (30 stimulations at 0.4 Hz, two runs). Both anticholinergic drugs reduced by a similiar amount the contraction amplitudes (TC 17 mmHg, BIP 25 mmHg, saline 67 mmHg; P < 0.01) and the rate of secondary contractions (TC 60%, BIP 70%, saline 95%; P < 0.01). In contrast, only biperiden prolonged the latencies of the evoked potentials (N1 peak, distal oesophagus: BIP 191 ms, TC 102 ms, saline 101 ms; P < 0.01; P1 peak: BIP 322 ms, TC 161 ms, saline 144 ms; P < 0.01). Both anticholinergic drugs depress oesophageal motility, but only the centrally-acting anticholinergic drug biperiden modifies the oesophageal evoked potentials, suggesting a central cholinergic transmission of the oesophageal afferent pathways.",1998.0,0,0
325,9863850,Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial.,K L Burgio; J L Locher; P S Goode; J M Hardin; B J McDowell; M Dombrowski; D Candib,"Urinary incontinence is a common condition caused by many factors with several treatment options. To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women. Randomized placebo-controlled trial conducted from 1989 to 1995. University-based outpatient geriatric medicine clinic. A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia. Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition. Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment. For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% ""much better"" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups. Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.",2001.0,0,0
326,9916307,Column switching in capillary liquid chromatography-tandem mass spectrometry for the quantitation of pg/ml concentrations of the free basic drug tolterodine and its active 5-hydroxymethyl metabolite in microliter volumes of plasma.,R Swart; P Koivisto; K E Markides,"A capillary column switching system was developed for the determination of low, unbound concentrations of the basic drug tolterodine and its active 5-hydroxymethyl (5-HM) metabolite in human plasma. Free concentrations of tolterodine and 5-HM at pM and nM (pg/ml and ng/ml) levels were obtained by ultrafiltration of 40-400 microliters plasma at 37 degrees C. The free fraction (%) was independent of the plasma concentrations of the analytes. Detection of the analytes was performed by sheathless electrospray tandem mass spectrometry in the multiple-reaction monitoring mode. The selectivity of the mass spectrometric detection and the additional clean-up on the pre-column allowed direct injection of the ultrafiltrated plasma samples. Tolterodine and 5-HM were pre-concentrated on a reversed-phase capillary pre-column (1 cm x 200 microns) and subsequently backflushed onto the separation column (25 cm x 200 microns). The stability of the chromatographic system was good; a large number of ultrafiltrated plasma samples could be injected and the relative standard deviation of the retention times was typically < or = 1% (within-day). The accuracy was between 86 and 105% and the precision was between 1 and 7% without the use of an internal standard. Linear calibration curves were obtained between 100 pM and 100 nM.",1999.0,0,0
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