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At least 163 records · Page 9Linked to original sources

PubMed2006

Daily intravesical instillation of 1 mg nociceptin/orphanin FQ for the control of neurogenic detrusor overactivity: a multicenter, placebo controlled, randomized exploratory study.

PURPOSE: We studied the feasibility, safety and efficacy of daily intravesical instillation of 1 mg of the endogenous peptide nociceptin/orphanin FQ in a selected group of patients who perform clean intermittent self-catheterization for neurogenic detrusor overactivity incontinence. MATERIALS AND METHODS: A total of 18 patients with neurogenic detrusor overactivity incontinence and on clean intermittent self-catheterization were prospectively randomized to receive 1 mg nociceptin/orphanin FQ in 10 cc saline (9) or placebo (saline) solution (9) at the first morning catheterization for 10 days. All patients completed a voiding diary using a frequency/volume chart according to International Continence Society guidelines, and reported daily incontinence frequency. Mean changes in incontinence episode frequency and voiding diary mean bladder capacity from baseline throughout treatment were the primary outcome variables. Urodynamic parameters (cystomanometric bladder capacity, maximum bladder pressure) were also recorded at baseline and during the study. RESULTS: The 2 groups were well balanced and all patients completed the study. The urodynamic parameters recorded during the study showed an increase in cystomanometric bladder capacity and a decrease in maximum bladder pressure compared to baseline only in patients assigned to the nociceptin/orphanin FQ group. Mean daily urine leakage episodes during nociceptin/orphanin FQ treatment were 0.94 vs a pretreatment baseline of 2.18 (p < 0.05), while no significant changes were reported in the placebo group (2.06 vs 2.43 baseline). The total mean voiding diary bladder capacity increased from 171 +/- 70 to 294 +/- 107 ml in patients receiving nociceptin/orphanin FQ, while voiding diary mean bladder capacity remained unchanged in patients receiving placebo (from 182 +/- 55 to 178 +/- 23 ml). No significant problems related to feasibility of the procedure as well as significant side effects were reported by patients. CONCLUSIONS: This study showed that intravesical nociceptin/orphanin FQ but not placebo inhibited the micturition reflex in patients with neurogenic detrusor overactivity incontinence, and demonstrated the clinical efficacy of nociceptin/orphanin FQ during 10 days of treatment. These findings support the use of nociceptin/orphanin FQ peptide receptor agonists as an innovative therapeutic approach for controlling detrusor overactivity incontinence.

Administration, Intravesical↗

PubMed2006

Propiverine compared to oxybutynin in neurogenic detrusor overactivity--results of a randomized, double-blind, multicenter clinical study.

OBJECTIVES: To compare the efficacy and tolerability of propiverine and oxybutynin in patients with neurogenic detrusor overactivity. METHODS: Patients were eligible, if at least 18 years of age and suffering from neurogenic detrusor overactivity. Eligibility also required a maximum cystometric capacity less than 300 ml. After a one-week run-in period, propiverine 15 mg t.i.d. or oxybutynin 5mg t.i.d. were administered for 21 days. As primary efficacy outcomes urodynamic parameters were assessed. As tolerability outcome the percentage of patients with newly manifesting anticholinergic adverse events was taken. RESULTS: 131 patients were recruited at 20 study centers. The maximum cystometric capacity (ml) was increased significantly in the propiverine group from 198 (+/-110) to 309 (+/-166), and in the oxybutynin group from 164 (+/-64) to 298 (+/-125). Similarly, maximum detrusor pressure during the filling phase (cm H(2)O) was lowered significantly in the propiverine group from 56.8 (+/-36.2) to 37.8 (+/-31.6), and in the oxybutynin group from 68.6 (+/-34.5) to 43.1 (+/-29.2). No significant differences resulted between treatment groups. Anticholinergic adverse events were reported less frequently in the propiverine compared to the oxybutynin group (63.0% versus 77.8%). Dryness of the mouth, the most frequent adverse event, was reported significantly less (47.1% versus 67.2%; p=0.02) in the propiverine compared to the oxybutynin group. CONCLUSION: Propiverine and oxybutynin are equally effective in increasing bladder capacity and lowering bladder pressure in patients with neurogenic detrusor overactivity. The trend for better tolerability of propiverine compared to oxybutynin achieved significance for dryness of the mouth.

Adolescent↗

PubMed2001

Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Aged↗

PubMed2007

Intravesical atropine compared to oral oxybutynin for neurogenic detrusor overactivity: a double-blind, randomized crossover trial.

PURPOSE: We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis. MATERIALS AND METHODS: We performed a study to determine the most effective dose of atropine. Eight participants used increasing doses of intravesical atropine during a 12-day period. Bladder diary data showed that the instillation of 6 mg atropine 4 times daily was most effective for increasing bladder capacity (voided/catheter volumes). We then did a randomized, double-blind crossover trial. Participants received 14 days of treatment with oral oxybutynin or with intravesical atropine, followed by 14 days of alternative treatment. Participants recorded a bladder diary and rated side effects and quality of life. The primary outcome variable was bladder capacity. RESULTS: A total of 57 participants with multiple sclerosis completed the study. Average change in bladder capacity was higher in the atropine arm. The mean +/- SD oxybutynin change was 55.5 +/- 67.2 ml, the mean atropine change was 79.6 +/- 89.6 ml and the mean difference between arms was 24.1 ml (95% CI -0.4, 49.7; p = 0.053). Changes in incontinence events and voiding frequency were not statistically different between the arms. Changes in total side effect and dry mouth scores were significantly better in the atropine treatment arm. CONCLUSIONS: Intravesical atropine was as effective as oxybutynin immediate release for increasing bladder capacity and it was probably better with less antimuscarinic side effects. We recommend that intravesical atropine should be made available to patients with neurogenic detrusor overactivity and voiding problems requiring intermittent catheterization as an alternative to oral therapy, which often has troublesome side effects.

Administration, Intravesical↗

PubMed2006

Bladder diary volume per void measurements in detrusor overactivity.

PURPOSE: We investigated the clinical usefulness of adjusting reference volume per void values for a recently reported strong tendency for volume per void to increase with increasing 24-hour volume in asymptomatic individuals. Our approach was to 1) test whether the adjustment increases the separation between volume per void measurements in patients with detrusor overactivity and an asymptomatic reference population, and 2) compare by regression analysis volume per void vs 24-hour volume relationships in patients with detrusor overactivity and asymptomatic volunteers. MATERIALS AND METHODS: We studied 3-day bladder diaries in 29 patients with detrusor overactivity and without genuine stress incontinence, an age matched control group of 29 asymptomatic women and a reference population of 161 asymptomatic women. Minimum, maximum and average volume per void measurements were calculated. The incidence of volume per void measurements below the 10th reference percentile was used as the measure of separation between the detrusor overactivity and asymptomatic populations. RESULTS: In patients with detrusor overactivity volume per void showed a highly significant positive relationship to 24-hour volume (p <0.0005). However, patient data points tended to lie below and parallel to control data points. Adjusting for the 24-hour volume relationship significantly increased the incidence of volume per void measurements below the 10th reference percentile in patients with detrusor overactivity (p <0.01). CONCLUSIONS: Adjusting for the 24-hour volume relationship increased the separation of patients with detrusor overactivity volume per void measurements from the reference population. Adjusting volume per void percentiles for the 24-hour volume relationship decreased the incidence of false-negative volume per void percentiles above the 10th percentile in patients with detrusor overactivity and false-positive volume per void percentiles below the 10th percentile in asymptomatic volunteers.

Adult↗

PubMed2006

Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: a double blind controlled randomized study.

AIMS: Many studies report the use of alcoholic capsaicin instillation to treat neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple sclerosis (MS) patients. However, poor tolerability due to the irritative effect of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy and tolerability of a new formulation of capsaicin in a glucidic solution in a multicenter clinical trial. MATERIALS AND METHODS: Thirty-three patients (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were prospectively enrolled in a double-blind placebo controlled study and randomized to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively received an intravesical instillation of 100 ml capsaicin diluted in glucidic solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30 and 90. RESULTS: On D0, groups were homogeneous. On D30, significant improvement of overactive bladder syndrome and an increase in MCC were shown in CG, whereas there were no improvement in SG. No significant improvement was shown on D90 in both groups. There were no significant differences between groups regarding prevalence, duration, or intensity of side effects, except for short duration pubic pain during instillation more often reported in CG (58.8%) than in SG (12.5%) (P < 0.01). CONCLUSION: This placebo controlled study using glucidic capsaicin confirms its short-term efficacy in NDO patients. Global tolerance of glucidic capsaicin appeared satisfactory. Long-term efficacy and tolerance of repeated glucidic capsaicin instillations need to be evaluated.

Adult↗

PubMed2006

Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats.

PURPOSE: The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity. METHODS: Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON. RESULTS: Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters. CONCLUSIONS: These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

Analysis of Variance↗

PubMed2004

Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment.

OBJECTIVE: To compare PGP9.5 and transient receptor potential vanilloid receptor (TRPV1) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, as suburothelial PGP9.5-staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin, and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder. PATIENTS AND METHODS: Patients with refractory NDO were enrolled in a prospective, randomized, parallel-group, double-blind, placebo-controlled trial using escalating doses of resiniferatoxin to a maximum of 1 micro mol/L. Flexible cystoscopic bladder biopsies obtained at baseline, 4 weeks after each instillation and at the time of maximum clinical response were compared with biopsies taken from control subjects. Frozen sections were incubated with rabbit antibodies to TRPV1 and PGP9.5, and assessed using standard immunohistochemical methods. PGP9.5 nerve density was analysed using a nerve-counting graticule by an observer unaware of sample origin. Another two independent observers unaware of each other's results used a random grading scale to evaluate TRPV1 nerve fibre density and intensity. The immunohistochemistry results were compared with histology findings (haematoxylin-eosin), and the Mann-Whitney test used to assess any differences (P < 0.05 significant) and the Pearson test for correlation. RESULTS: There were eight controls and 20 patients with spinal NDO, 14 (five clinical responders and nine not) who received the maximum dose of resiniferatoxin. There were more PGP9.5 and TRPV1 nerve fibres in patients with NDO than in controls (P = 0.007 and 0.002, respectively). Immunoreactivity before resiniferatoxin was similar in both groups for both PGP9.5 and TRPV1. In responders there were fewer PGP9.5 and TRPV1-positive fibres after treatment (P = 0.008 for each) but no change in those not responding. Changes after treatment for TRPV1 correlated well with those for PGP9.5 (r = 0.88, P < 0.001). CONCLUSIONS: The decrease of PGP9.5 and TRPV1 immunoreactive nerve fibres in responders to resiniferatoxin (to levels in control tissues) suggests that the increased numbers of nerve fibres in patients with NDO are mainly of sensory origin and express TRPV1. As baseline nerve fibre values were similar in responders and nonresponders, an additional factor may account for the difference in treatment outcome.

Administration, Intravesical↗

PubMed2006

Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor.

OBJECTIVE: To investigate the effects of a selective type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor, IC486051, on bladder activity in normal rats and those with and bladder outlet obstruction (BOO), as inhibition of PDE4 leads to elevation of intracellular cAMP levels and relaxation of smooth muscle. MATERIALS AND METHODS: BOO was induced in female Sprague-Dawley rats by tying a silk ligature around the urethra. At 4 or 6 weeks after inducing BOO, conscious rats were assessed by cystometry with the urethral ligature intact. In unobstructed rats, blood pressure was also measured. RESULTS: In unobstructed rats, IC486051 (0.1 mg/kg intravenously) produced no significant changes in cystometric variables, while at a dose of 0.5 mg/kg maximum voiding pressure was reduced by 34%. At both doses, there was a small, transient increase in blood pressure. In both 4- and 6-week BOO rats IC486051 dose-dependently decreased the number and amplitude of non-voiding bladder contractions by up to 80%, relative to pre-treatment values. At doses of 0.1 and 0.5 mg/kg IC486051 had no significant effect on voiding variables. In the 4-week BOO rats, a dose of 1.0 mg/kg decreased bladder capacity, voided volume and residual volume by 21%, 32% and 18%, respectively. In 6-week BOO rats, a dose of 1.0 mg/kg decreased maximal voiding pressure by 17% and pressure threshold for voiding by 28%. In both groups of rats with BOO, voiding efficiency was unchanged. CONCLUSIONS: A selective PDE4 inhibitor can effectively suppress detrusor overactivity in rats with BOO, at doses that have no effect on voiding bladder contractions. Thus, selective PDE4 inhibitors should be considered for the treatment of overactive bladder in patients with BOO.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

[Treatment of overactive bladder with sodium chondroitin sulphate].

OBJECTIVE: It is not always possible to clearly differentiate the symptoms of overactive bladder and interstitial cystitis. A prospective randomized study was performed to determine whether instillation of sodium chondroitin sulphate for treatment of interstitial cystitis is also effective in treating overactive bladder. The expected benefit of this therapeutic approach in overactive bladder is based on the assumption that the glycosaminoglycan layer may be damaged in overactive bladder as well. MATERIAL AND METHODS: Patients with chronic overactive bladder were randomized to one of two study groups each including 41 patients. Group A was treated with an anticholinergic agent (tolterodine), group B with sodium chondroitin sulphate (Uropol S). The diagnosis was established on the basis of a gynecologic examination and history, urodynamic testing, introital ultrasound, and cystoscopy. Patients were treated for 12 months. RESULTS: An improvement of symptoms was reported by 15/35 (43 %) of the patients in group A (p = 0.000) as compared with 23/32 (72 %) of the patients in group B. The subjective outcome was corroborated by means of urodynamic testing, number of pads used, voiding frequency, and nycturia (voiding diary). Quality of life increased significantly in both groups in the course of treatment but there was no significant difference between both groups. CONCLUSION: The results of the study presented here suggest that restoring the glycosaminoglycan layer also improves or cures the symptoms in patients with overactive bladder. Patients clearly benefit from instillation of sodium chondroitin sulphate. These results must be confirmed in larger studies before a wider use of this therapeutic option can be recommended.

Cholinergic Antagonists↗

PubMed2006

Human idiopathic and neurogenic overactive bladders and the role of M2 muscarinic receptors in contraction.

OBJECTIVES: This study examines whether M(2) receptors contribute to direct contraction of the detrusor in human neurogenic and idiopathic overactive bladders. METHODS: Control detrusor muscle was obtained from patients undergoing cystectomy for bladder cancer, whilst overactive detrusor muscle was obtained from patients undergoing clam cystoplasty for idiopathic or neurogenic detrusor overactivity. The affinities of a range of subtype selective antagonists (DAMP, darifenacin, methoctramine R0-320-6206, and pirenzepine) were obtained in tissue bath experiments by using carbachol as the agonist. These affinity values were then compared with the known affinities for these antagonists at the muscarinic receptor subtypes. RESULTS: An increased sensitivity to carbachol was observed in both the neurogenic and idiopathic overactive detrusors compared with the control human detrusor. The M(2)-selective antagonists (methoctramine, R0-320-6206) and M(1)-selective antagonist (pirenzepine) had low affinities, whilst the M(3)-selective antagonists (4-DAMP and darifenacin) had high affinities for the human detrusor muscarinic receptor in all three groups of tissues. The affinities (pK(B) values) for the five antagonists were consistent with antagonisms at the M(3) receptor in all three groups; Schild plot analysis indicated an action at this single receptor subtype. CONCLUSIONS: Contraction mediated by muscarinic receptors is enhanced in idiopathic and neurogenic overactive detrusors compared with control detrusor. The direct contractile response to carbachol is mediated by the M(3) receptor in both human normal and overactive bladders, indicating no change in receptor subtype contribution to contraction in the disease state.

Adult↗

PubMed2006

Propiverine hydrochloride immediate and extended release: comparison of efficacy and tolerability in patients with overactive bladder.

INTRODUCTION: This study aims to compare the efficacy of propiverine hydrochloride immediate release (IR), propiverine hydrochloride extended release (ER) and placebo for the treatment of overactive bladder syndrome. The primary outcome measure is incontinence episode frequency, with secondary outcome measures including mean volume per void and quality of life as assessed on King's Health Questionnaire. MATERIAL AND METHODS: The double-blind, double-dummy, randomized study compared IR 15 mg twice daily, ER 30 mg once daily and placebo in 3 parallel groups. After a run-in period of 7 days, the patients were treated for 32 days. Nine hundred and eighty-eight patients were randomized, and 910 patients completed the protocol without major violations. RESULTS: The number of incontinence episodes/24 h decreased by 2.26 in the IR group (p < 0.001 vs. placebo), by 2.46 in the ER group (p < 0.0001 vs. placebo) and by 1.75 in the placebo group. The most frequent adverse event was dry mouth with 22.8% of the patients in the IR group, 21.7% in the ER group and 6.4% in the placebo group. The overall tolerability was rated 'very good' or 'good' by more than 80% of the investigators and patients in all 3 groups. CONCLUSIONS: Propiverine ER 30 mg once daily and propiverine IR 15 mg twice daily significantly reduce the number of incontinence episodes/24 h within a treatment period of 32 days. Both formulations are safe and well tolerated. The extended release formulation of propiverine is a suitable new option for the treatment of the overactive bladder.

Benzilates↗

PubMed2006

Effect of the potassium channel opener WAY-133537 on the overactive bladder of spinalized rats.

AIMS: To test the efficacy of WAY-133537 for the treatment of overactive bladder (OAB) in a chronic paraplegic rat model. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were used in this study. Six animals served as normal controls (without spinal cord transaction (ST)), while 42 rats underwent ST at the 10th thoracic vertebra. Two weeks after ST, cystometrogram (CMG) was performed in six randomly chosen animals to ensure the development of neurogenic detrusor overactivity. The remaining 36 rats were divided into three equal groups, 12 received the vehicle as "paraplegic controls," 12 received WAY-133537 0.3 mg/kg, and 12 received WAY-133537 3 mg/kg. Each "paraplegic control" and treatment group was further divided into two sub-groups (n = 6), with CMG at 3 and 4 weeks after ST, respectively. RESULTS: Two weeks after ST, all "vehicle control" rats developed detrusor overactivity with a mean frequency of 0.96 and 1.48 contractions/min and amplitude of 22.96 and 31.22 cm H(2)O with 1- and 2-week treatment, respectively. Neurogenic detrusor overactivity disappeared from 50% of rats that received WAY-133537 0.3 mg/kg for 1 week, and frequency decreased to 0.41 contractions/min. After 2 weeks of treatment, detrusor overactivity vanished from 67% of the animals with even further reduction in the frequency of detrusor overactivity (0.22 contractions/min, P < 0.01). In rats that received 3 mg/kg of the drug for 1 week, detrusor overactivity disappeared from only one animal with a non-significant decline in frequency. Fifty percent of rats given WAY-133537 at the dose of 3 mg/kg/day for 2 weeks manifested no detrusor overactivity. CONCLUSIONS: WAY-133537 shows efficacy in increasing bladder capacity and reducing the frequency of spontaneous bladder contractions after ST in rats without decreasing voiding pressure.

Animals↗

PubMed2006

Efficacy, tolerability and safety of propiverine hydrochloride in children and adolescents with congenital or traumatic neurogenic detrusor overactivity--a retrospective study.

OBJECTIVES: Anticholinergic treatment combined with intermittent catheterisation is the cornerstone of the conservative treatment strategy in children with neurogenic detrusor overactivity, which in most cases is due to congenital causes. Efficacy, tolerability and safety of propiverine hydrochloride were evaluated retrospectively in these children. METHODS: At four specialized outpatient clinics, all children's records were scrutinized for first-line propiverine hydrochloride treatment, or second- or third-line treatment after failure of a non-selective alpha-blocker (phenoxybenzamine) and/or other anticholinergics (oxybutynin, trospium chloride). The primary efficacy outcomes were urodynamic parameters, with clinical symptoms as secondary outcomes. Statistical analysis was performed by paired t-tests (significance level p < 0.05). RESULTS: Altogether 74 children and adolescents (40 boys, 34 girls; age range 11 months-19 years) were treated with propiverine hydrochloride (average duration 2 years and approximately 4 months; individual dose range 5-75 mg). The primary efficacy outcome parameters improved significantly: maximum cystometric capacity 161.2 [standard deviation (SD) 97.3] to 252.2 ml (SD 117.2), p < 0.001; maximum detrusor pressure 43.8 (SD 39.2) to 27.1 cm H(2)O (SD 26.4), p = 0.002; bladder compliance 7.6 (SD 6.4) to 17.0 ml/cm H(2)O (SD 16.2), p < 0.001. Phasic detrusor overactivity was abolished by 63%; incontinence resolved by 54%. One patient spontaneously reported a typical anticholinergic adverse event, which resolved after dose reduction. No safety concerns were documented. CONCLUSIONS: Propiverine hydrochloride is effective in neurogenic detrusor overactivity in children and adolescents, even in some of those cases unresponsive to other anticholinergics. The low incidence rate (<1.5%) of adverse events evidences a favourable risk-benefit profile of propiverine hydrochloride, considering in particular the total documented treatment and surveillance period of 171 patient years and nine months.

Adolescent↗

PubMed2006

Local effects of antimuscarinics.

Overactive bladder (OAB) syndrome has been estimated to occur in nearly 17% of the population. The most common drug treatments for OAB are antimuscarinic agents that act to increase bladder capacity and decrease the urge to urinate during the storage phase. An increasing number of studies have focused on te role and mechanism of muscarinic acetylcholine receptors for the regulation of afferent activity during urine storage. Interactions between muscarinic receptors in the urothelium, afferent nerves, or myofibroblasts and locally released acetylcholine might be involved in the emergence of detrusor overactivity and OAB. Therefore, antimuscarinic agents may be effective in treating OAB not only by suppression of muscarinic receptor-mediated detrusor muscle contractions but also by modulation of muscarinic receptor-bladder afferent interactions.

Humans↗

PubMed2006

Solifenacin.

Pharacologic therapy has been the mainstay of treatment for patients who have overactive bladder. In recent years, a number of new antimuscarinic agents have been introduced. Solifenacin succinate is a new once-daily antimuscarinic agent that is an effective and well-tolerated treatment option for patients who have overactive bladder. Solifenacin increases functional bladder capacity and decreases urgency, frequency, and incontinence. In pharmacokinetic studies, solifenacin demonstrated selectivity for the bladder over the salivary gland; thus, it is likely that the bladder selectivity of this agent is responsible for the low incidence of dry mouth and constipation reported in the clinical trials.

Clinical Trials as Topic↗

PubMed2006

Symptom change in women with overactive bladder after extracorporeal magnetic stimulation: a prospective trial.

The purpose of this study was to prospectively evaluate symptom change after discontinuation of extracorporeal magnetic stimulation (EMS) in women with overactive bladder (OAB). A total of 48 women with OAB were included. We applied 10 Hz of repetitive magnetic stimulation with a "magnetic chair" for 20 min, twice weekly for 8 weeks. Changes in OAB symptoms at 2, 12, and 24 weeks after discontinuing the EMS were evaluated. Twenty-seven (56.3%) patients were cured compared with the baseline at 2 weeks: the cure rate was determined as 68.8% (33/48 patients), 56.3% (27/48), and 50% (8/16) for urgency, frequency, and urge incontinence, respectively. The mean number of voids per 24 h was decreased by 42.8% (from 14.5 +/- 4.3, to 8.3 +/- 1.5, P < 0.001) at 2 weeks after treatment. Maximum voided volume did not change significantly, but the mean voided volume increased significantly after stimulation. Twenty-six (96.3%) patients among the 27 patients who achieved a cure at 2 weeks, maintained improvement at 24 weeks; the therapeutic effect on urgency, frequency, and urge incontinence persisted in 26 (78.8%) of 33 patients, 26 (96.3%) of 27 patients, and six (75%) of eight patients, respectively. There were no significant changes in urodynamic parameters. Of the 14 patients with detrusor overactivity, the condition was no longer observed in four (28.6%) patients. EMS has a beneficial effect on women with OAB. Our data suggest EMS may have a significant carry-over effect in well-selected OAB patients.

Adolescent↗

PubMed2006

The association between T-type Ca2+ current and outward current in isolated human detrusor cells from stable and overactive bladders.

OBJECTIVE: To determine if bladder overactivity in humans is associated with an altered activity of Ca(2+) channels in detrusor smooth muscle and the consequent activation of other ion channels. MATERIAL AND METHODS: Samples of bladder were obtained from patients with urodynamically stable bladders, or with idiopathic detrusor overactivity. Isolated cells were patch-clamped with pipettes containing a Cs(+)-based filling solution to isolate inward currents, or a K(+)-filling solution to measure outward current. Components of inward current were separated according to their sensitivity to NiCl(2) (< or =100 microm) and nifedipine. RESULTS: Ni(2+)-sensitive (T-type) and nifedipine-sensitive (L-type) current was recorded in all cells. The voltage- and time-dependent properties were similar in cells from both patient groups. However, the current density of the L-type current was less, and that of the T-type current was greater, in myocytes from overactive bladders. In cells from overactive bladders, the mean K(+) current over the range - 80 to - 50 mV was also higher than in control cells. This current was sensitive to the large-conductance channel modulator iberiotoxin and to NiCl(2) (100 microm) CONCLUSIONS: Detrusor myocytes from overactive human bladders have a higher T-type Ca(2+) current density; we propose that this increases transient outward currents, and so might contribute to higher levels of spontaneous activity.

Action Potentials↗