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Aim: To retrieve, analyse and summarize the relevant evidence on the prevention and management of bladder dysfunction in patients with cervical ancer after radical hysterectomy. Design: Overview of systematic reviews. Methods: 11 databases were searched for relevant studies from top to bottom according to the '6S' model of evidence‐based resources. Two independent reviewers selected the articles, extracted the data and appraised the quality of the included reviews based on different types of evaluation tools. Results: A total of 13 studies were identified, including four clinical consultants, four guidelines, four systematic reviews and one randomized controlled trial. 29 best evidence were summarized from five aspects, including definition, risk factors, assessment, prevention and management. [ABSTRACT FROM AUTHOR]

The aim of this publication is to disseminate the clinical practice guidelines for the treatment of intestinal, bladder/ureteral, thoracic and umbilical endometriosis, already published in Japanese, to non‐Japanese speakers. For developing the original Japanese guidelines, the clinical practice guideline committee was formed by the research team for extragenital endometriosis, which is part of the research program of intractable disease of the Japanese Ministry of Health, Labor and Welfare. The clinical practice guideline committee formulated eight clinical questions for the treatment of extragenital endometriosis, which were intestinal, bladder/ureteral, thoracic and umbilical endometriosis. The committee performed a systematic review of the literature to provide responses to clinical questions and developed clinical guidelines for extragenital endometriosis, according to the process proposed by the Medical Information Network Distribution Service. The recommendation level was determined using modified Delphi methods. The clinical practice guidelines were officially approved by the Japan Society of Obstetrics and Gynecology and the Japan Society of Endometriosis. This English version was translated from the Japanese version. [ABSTRACT FROM AUTHOR]

Summary: Up to 80% of patients with diabetes mellitus develop lower urinary tract complications, most commonly diabetic bladder dysfunction (DBD). The aim of this study was to investigate the impact of diabetes on the function of the inner bladder lining (urothelium). Bladder compliance and intraluminal release of urothelial mediators, adenosine triphosphate (ATP) and acetylcholine (ACh) in response to distension were investigated in whole bladders isolated from 2‐ and 12‐week streptozotocin (STZ)‐diabetic rats. Intact and urothelium‐denuded bladder strips were used to assess the influence of the urothelium on bladder contractility. Intraluminal ATP release was significantly enhanced at 2 weeks of diabetes, although not at 12 weeks. In contrast, intraluminal ACh release was unaltered by diabetes. Bladder compliance was also significantly enhanced at both 2 and 12 weeks of diabetes, with greatly reduced intravesical pressures in response to distension. Nerve‐evoked contractions of bladder strips were significantly greater at 2 weeks of diabetes. When the urothelium was absent, nerve‐evoked contractions were reduced, but contractions remained significantly elevated at lower frequencies of stimulation (<5 Hz) in diabetics. Interestingly, although relaxations of bladder strips to isoprenaline were unaltered by diabetes, removal of the urothelium unmasked significantly enhanced relaxations in strips from 2‐ and 12‐week diabetic animals. In conclusion, diabetes alters urothelial function. Enhanced urothelial ATP release may be involved in the hypercontractility observed at early time points of diabetes. These alterations are time‐dependent and may contribute to the mechanisms at play during the development of diabetic bladder dysfunction. [ABSTRACT FROM AUTHOR]

Background: Post-operative catheter-related bladder discomfort (CRBD) causes increased emergence agitation. Muscarinic receptor activation is a major mechanism in CRBD development. Experimental studies showed that sevoflurane has anti-muscarinic effects whereas propofol does not. Our hypothesis was that sevoflurane anaesthesia would reduce the incidence of CRBD following bladder surgery.Methods: In total, 82 patients undergoing transurethral bladder tumour excision (TURBT) were assigned randomly to two groups according to the maintenance anaesthetic agent received: sevoflurane (n = 41) or propofol (n = 41). The incidence of CRBD was evaluated at 0, 1, 6 and 24 h post-operatively. The number of patients treated with a rescue medication (tramadol) for CRBD was noted.Results: The incidence of CRBD at post-operative 1 h was lower in the sevoflurane group than that in the propofol group (59% vs. 85%; P = 0.007). The differences in CRBD were 27% and 22% at 0 and 6 h post-operatively (P = 0.008 and 0.047, respectively). CRBD occurred in 27 (66%) patients in the sevoflurane group vs. 38 (93%) in the propofol group from 0 to 24 h post-operatively (P = 0.005). The number of patients treated with tramadol was lower in the sevoflurane group (13 [22%] vs. 22 [54%]; P = 0.044).Conclusion: Sevoflurane, as a maintenance in general anaesthesia, decreased the incidence of early post-operative CRBD and tramadol requirements in patients undergoing TURBT, compared with propofol. [ABSTRACT FROM AUTHOR]

Objectives To explore whether serum and urinary advanced glycation end-products ( AGEs) are related to urinary symptoms and bladder dysfunctions in diabetic patients. Methods Forty-seven patients with type 2 Diabetes mellitus ( T2DM) and lower urinary tract symptoms ( LUTS) were enrolled. LUTS evaluation was performed by IPSS ( International Prostatic Symptoms Score), QoL ( quality of life), OAB ( overactive bladder). ICI-SF ( International Consultation on Incontinence - short form) quaestionneires; ultrasound examination, evaluation of postvoid residual ( PVR), uroflowmetry, cystometry with pressure-flow study ( PFS) were performed to detect bladder dysfunctions. Serum and urinary AGEs were quantified by ELISA method. Results Patients were divided into four subgroups: (i) normal-detrusor-contractility + normal- detrusor-activity (1 ♂ [4.8%] and 4 ♀ [21%]), (ii) impaired-detrusor-contractility + normal-detrusor- activity (4 ♂ [19.1%] and 0 ♀), (iii) normal-detrusor-contractility + detrusor-overactivity (1 ♂ [4.8%] and 6 ♀ [31.6%]), (iv) impaired-detrusor-contractility + detrusor-overactivity (15 ♂ [71.4%] and 9 ♀ [47.4%]). Serum AGEs were 12.2 ± 5.5 in men and 10.4 ± 5.6 in women; urinary AGEs were 1.5 ± 1.1 in men and 2.5 ± 1.6 in women. Serum AGEs exhibited a positive correlation with IPSS ( P < 0.05) and OAB-q scores ( P < 0.01). Increased serum AGEs were associated with a significant reduction in the parameters reflecting impaired detrusor contractility with simultaneous reductions of urinary AGEs ( P < 0.01). A greater correlation was observed between serum AGEs and subgroup 4 ( P < 0.05). Conclusions Serum AGEs seem to be early markers of diabetic complications and appear to be related to LUTS and bladder dysfunctions. [ABSTRACT FROM AUTHOR]

Objectives To investigate safety, tolerability and efficacy of long-term (52 weeks) open-label treatment with mirabegron 50 mg, with an optional dose increase to 100 mg, in patients with overactive bladder ( OAB). Methods Patients received mirabegron 50 mg once daily for 52 weeks. If efficacy was insufficient at week 8, the dose could be increased to 100 mg. Safety was evaluated based on vital signs, adverse events ( AEs), laboratory findings, electrocardiogram and post-void residual volume. Treatment efficacy was assessed with a 3-day micturition diary and the King's Health Questionnaire ( KHQ). Results Two hundred and four patients were enrolled; mirabegron dose was maintained at 50 mg in 153 patients and increased to 100 mg in 50 patients. Mirabegron was well tolerated at both doses. Incidences of AEs and treatment-related AEs were 91.4% and 33.6% in patients on 50 mg, and 100% and 30.0% in patients on 100 mg, respectively. Time course changes in systolic or diastolic blood pressure and pulse rate were not considered clinically significant. At the end of treatment ( EOT), patients on 50 mg and 100 mg showed improvement in frequency and urgency. Improvements from baseline to EOT in quality of life scores were observed for all KHQ domains. Conclusions There were no safety or tolerability concerns associated with mirabegron 50 mg (with an optional dose increase to 100 mg) over 52 weeks. Improvement in micturition variables was maintained with mirabegron 50 mg from weeks 8 to 52. [ABSTRACT FROM AUTHOR]

The alkylating anticancer drug, cyclophosphamide ( CP), induces a number of toxic effects including haemorrhagic cystitis ( HC) in the urinary bladder. Uroplakins are unique urinary transmembrane proteins of urothelium, which may become potential targets of CP metabolites and reactive free radicals. Natural compounds, especially those rich in thiols, have shown protective effects against CP-induced HC. In this study, we studied the modulatory effect of the thiol-rich compound S-allyl cysteine ( SAC) on the mRNA level of uroplakin II by real-time polymerase chain reaction and expression of uroplakin II protein by immunoblotting. SAC (150 mg/kg) showed significant ( p < 0.001) protective effects against CP (200 mg/kg)-induced alteration in mRNA level and protein expression of uroplakin II. SAC also protected animals from CP-induced HC as assessed by gross morphological examination of urinary bladder. When compared with mercaptoethane sulphonic acid (mesna) (40 mg/kg), a known thiol-rich drug used in clinical application, SAC was found to be more efficacious in affording protection in urinary bladder tissues. Role of uroplakins in CP-induced urinary bladder toxicity has not been well investigated. This study demonstrated that uroplakins may be the potential target of toxic metabolites of CP and natural compounds such as SAC have the capacity to modulate their expression leading to reduced toxicity burden on the urinary bladder epithelium. [ABSTRACT FROM AUTHOR]

In the last decades, a number of new antimuscarinic drugs have been introduced for treatment of the overactive bladder ( OAB), defined symptomatically ( OAB syndrome) or urodynamically (detrusor overactivity). Recently, three new drug principles have been approved for clinical use, the β3-adrenoceptor agonist, mirabegron, the phosphodiesterase-5 inhibitor, tadalafil and the blocker of afferent and efferent nerves, botulinum toxin. However, new alternatives are continuously being explored. OAB is a filling disorder, and ATP is involved in the generation of afferent impulses. One way of blocking the ATP afferent pathway is through the use of P2X3 receptor antagonists. In animal models, this strategy appears to work very well, but whether it translates effectively to man remains to be established. Evidence suggests that components of the endocannabinoid system are involved in regulation of bladder function. Clinical studies of cannabinoid extracts on LUTS are scarce and essentially restricted to patients with MS, and the results have so far not been convincing. Amplification of endocannabinoid activity by inhibiting their degradation via fatty acid amide hydrolase inhibitors may be an attractive approach, but no clinical experiences in OAB have been reported. Studies of the lower urinary tract have indicated that several transient receptor potential ( TRP) channels, including TRPV1, TRPV2, TRPV4, TRPM8 and TRPA1, are expressed in the bladder and may act as sensors of stretch and/or chemical irritation. Animal studies have shown that inhibition of these pathways can be effective for the reduction in bladder activity. However, the roles of these channels for normal function and in pathological states have not been established, and so far adverse effects (hyperthermia) have hampered development of antagonists. [ABSTRACT FROM AUTHOR]

Objectives To investigate the efficacy and complications of controlled transurethral resection and incision of the bladder neck to treat female primary bladder neck obstruction. Methods A total of 59 patients who were diagnosed with female primary bladder neck obstruction by urodynamic examination underwent surgical procedures at Urological Institute of the People's Liberation Army, First Affiliated Hospital of Third Military Medical University, Chongqing, China, between March 2010 and March 2014. For all patients, neurogenic, anatomical and dysfunctional voiding causes of bladder outlet obstruction had been excluded. Perioperative and follow-up data, including operative time, maximum urine flow rate, residual urine volume, International Prostate Symptom Score and Quality of Life Score, were prospectively investigated. Results All of the operations were completed uneventful. The median operative time was 15 ± 8 min (range 10-22 min). No massive hemorrhage or infection was reported. Follow-up data were available for 59, 59, and 57 of the patients at 1, 6 and 12 months postoperatively, respectively. The mean maximum urine flow rate increased from 7.2 ± 3.9 mL/s preoperatively to 26.1 ± 5.2 mL/s postoperatively. The mean residual urine volume decreased from 162 ± 75 to 20 ± 7 mL. The mean International Prostate Symptom Score decreased from 24.5 ± 7.2 to 5.5 ± 3.6. The mean Quality of Life Score decreased from 5.4 ± 1.7 to 1.9 ± 1.1. All of the differences between the preoperative and postoperative values were significant ( P < 0.001). Conclusions The novel technique described here shortens the length of the urethra to 2.5 cm, which both released the obstruction and maintained continence. The results of the present preliminary study show that this method represents a safe and effective treatment for female primary bladder neck obstruction. [ABSTRACT FROM AUTHOR]

Bladder outlet obstruction ( BOO) should be considered when a woman complains of voiding difficulty, abdominal straining to void, or refractory storage symptoms. Diagnosis of female BOO is not straightforward and usually requires invasive (video)urodyanmic study. A diagnostic algorithm is recommended for making optimal diagnosis. Female BOO can be classified as having anatomical and functional origins, and each contains several sub-classifications. Literatures published between 1988 and 2013 were reviewed and summarized for the diagnosis and therapy in each subtype of female BOO. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. Methods: The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. Results: A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs 50%, P = 0.88). Conclusion: After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. [ABSTRACT FROM AUTHOR]

Objectives To investigate the clinical importance of paraureteral diverticulum in the management of vesicoureteral reflux by analyzing the relationship between paraureteral diverticulum and recurrent urinary tract infections. Methods We retrospectively reviewed 131 children diagnosed with vesicoureteral reflux. We diagnosed vesicoureteral reflux and paraureteral diverticulum by initial voiding cystourethrography and defined 'delayed ureteral drainage' as the presence of contrast media in the upper urinary tract on delayed films after voiding. We analyzed the relationships between paraureteral diverticulum, delayed ureteral drainage and recurrent urinary tract infections. Results The mean age at diagnosis of vesicoureteral reflux was 20.7 months. Of the 202 refluxing ureters, 55 (27.2%) had a paraureteral diverticulum. Of the 55 ureters with paraureteral diverticulum, 51 (92.7%) showed delayed ureteral drainage of refluxing contrast, which was significantly higher than the percentage of delayed ureteral drainage in ureters without paraureteral diverticulum ( P < 0.001). On multivariate analysis of the effect of reflux grade or paraureteral diverticulum on delayed ureteral drainage of refluxing contrast, the odds ratio of paraureteral diverticulum was 11.47 ( P < 0.001). In addition, the risk of recurrent urinary tract infections increased in ureters with paraureteral diverticulum ( P = 0.020). Conclusions In patients with vesicoureteral reflux and paraureteral diverticulum, the risk of recurrent febrile urinary tract infections seems to increase. Therefore, more progressive surveillance and treatment protocols should be considered in these patients. [ABSTRACT FROM AUTHOR]

Objectives To determine whether botulinum toxin type A can represent an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies. Methods This is a single-center, prospective, open labeled, randomized comparative study. Patients with refractory interstitial cystitis were randomly divided into two groups: immediate injection (group A) or 1-month delayed injection (group B) of botulinum toxin type A after allocation. The rate of treatment response (global response assessment ≥+1: slightly improved), and changes in symptom scores and frequency volume chart variables were compared between groups 1 month after allocation. Using subjects of both groups as a single cohort, predictive factors for treatment response at 1 month post-injection and the duration of response were explored. Results A total of 34 patients (group A n = 18, group B n = 16) were allocated. The response rate was significantly higher in group A than group B (72.2% vs 25.0%, P = 0.01). All symptom measures showed significant improvement in group A than group B. When both groups were combined as a single cohort, the response rate was 73.5% at 1 month, 58.8% at 3 months, 38.2% at 6 months and 20.6% at 12 months. The mean duration of response was 5.4 months. Multivariate analysis showed that past exposure to hydrodistension more than three times correlated with better outcomes. Conclusions Botulinum toxin type A injection could be an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies, especially for those who have received repeated hydrodistensions and transurethral fulguration. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of urine alkalization therapy using citrates in patients with hypersensitive bladder syndrome. Methods A total of 76 patients with urinary frequency were assessed for their symptoms using a 2-day voiding diary as well as the urine pH at each voiding during the screening period. Their symptoms were also assessed by pain score, King's health questionnaire, and O' Leary- Sant symptom and problem index scores. Finally, 50 patients were evaluated for changes in symptoms after oral treatment with citrates for 2-4 weeks after the screening period. Results After the treatment, significant increases in the urine pH (from 5.8 ± 0.4 to 6.3 ± 0.4; increment of 0.5 ± 0.4; P < 0.01), and significant decreases in the number of micturitions per day (from 14.5 ± 6.5 to 13.5 ± 5.9; P = 0.02) and the number of episodes of pain/discomfort per day (from 7.8 ± 6.8 to 6.1 ± 7.1; P = 0.02) were observed. In the King's health questionnaire, the sleep/energy domain score was significantly improved (from 60.0 ± 25.0 to 50.3 ± 29.6; P < 0.01). In a subgroup analysis based on urine pH (urine pH <6.2 and ≥6.2), significant improvements in the voiding symptoms, the sleep/energy domain score and the O' Leary- Sant problem index were observed in the group with urine pH of ≥6.2. There were statistically significant differences between the subgroups in the volume per voiding, maximum volume per voiding and the problem index. In addition, the subgroup, in which patients had pain in the screening period, showed statistically significant improvements in the number of micturitions per day, episodes of pain/discomfort per day, the sleep/energy domain score and the problem index. Conclusions Urine alkalization therapy is likely to be effective in the treatment for hypersensitive bladder syndrome. [ABSTRACT FROM AUTHOR]

Objectives To study the effects of partial bladder outlet obstruction on the cell's anti-oxidant defense mechanisms, superoxide dismutase and catalase, in order to elucidate how the bladder responds to oxidative stress. Methods Four groups of eight rabbits were subjected to partial bladder outlet obstruction for 4, 8 and 12 weeks. Eight sham rabbits were used as the control group. The bladders were removed under anesthesia, and the muscle and mucosa were separated, frozen and stored at −80° C for analysis. Superoxide dismutase and catalase assays were carried out on these tissues. The groups were also categorized by severity (mild, intermediate and severe) of decompensation, as well as duration. Results When separated by duration, catalase activity of the mucosa was significantly higher in the control and the 12-weeks obstructed rabbits. This activity was lower than the control in the 4- and 8-weeks obstructed rabbits. When separated by severity, catalase activity of the mucosa was significantly higher and severely decompensated than the muscle in the controls. When separated by duration or severity, superoxide dismutase activity of the muscle was significantly lower than controls for all obstructed rabbits. The activities of both superoxide dismutase and catalase were significantly reduced in the severely decompensated bladder smooth muscle, but not in the 12-weeks obstructed bladder smooth muscle. Conclusions Partial bladder outlet obstruction has significant effects on the activity of both superoxide dismutase and catalase in the bladder, with variations that are dependent on the severity and duration of the obstruction. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of the Rho kinase inhibitor, hydroxyfasudil, on bladder function in a rat model of HCl-induced chemical cystitis, and to elucidate the possible mechanisms associated with its therapeutic effect. Methods Female Sprague- Dawley rats with HCl-induced cystitis were given hydroxyfasudil (10 mg/kg, i.p.) for 7 days. Treatment efficacy was determined by comparing bladder function and histopathology to sham and untreated control rats. Bladder function was determined by cystometric analysis. Rho kinase activity was determined by quantitative reverse transcription polymerase chain reaction and signal inhibition of downstream Ras homolog member A/ Rho kinase signaling molecules by western blot and immunohistochemistry. Results Treatment with hydroxyfasudil significantly improved bladder intercontraction intervals. Rats treated with hydroxyfasudil also showed a significant reduction of histopathological features associated with cystitis. Western blot and immunohistochemistry findings showed that hydroxyfasudil inhibited downstream molecules of Rho kinase that ameliorated changes associated with HCl-induced chemical cystitis, such as inflammatory cell recruitment and smooth muscle cell proliferation. Conclusion The findings from the present study suggest a promising therapeutic role for hydroxyfasudil in bladder inflammation associated with cystitis. [ABSTRACT FROM AUTHOR]

Botulinum toxin A is available under three different protein complexes that are not interchangeable until appropriate comparative studies are undertaken. The best studied for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity and overactive bladder/idiopathic detrusor overactivity is onabotulinum toxin A. This brand is only approved for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity at a dose of 200 U and idiopathic detrusor overactivity at a dose of 100 U. In patients with detrusor overactivity as a result of spinal cord injury or multiple sclerosis, 200 U of onabotulinum toxin A should be injected in 30 different sites above the trigone. It was shown to be highly effective in curing or decreasing urinary symptoms of incontinence, increasing quality of life, increasing bladder capacity and decreasing maximal detrusor pressure. This effect was independent of the concomitant use of oral anticholinergic drugs. Adverse events were mild, mainly urinary tract infections and high postvoid residual requiring clean intermittent catheterization. In patients with overactive bladder/idiopathic detrusor overactivity, 100 U of onabotulinum toxin A should be injected in 20 sites above the trigone. It markedly decreases urinary incontinence and improves quality of life. Frequency and urgency episodes are also decreased. Adverse events are mild, mainly urinary tract infections and urinary retention. The latter occurred in just 5% of the patients. Candidates for onabotulinum toxin A treatment should be warned that the effect of the toxin is transient and that repeated injections will be required to maintain the effect in the long term. There is no evidence that repeated injections will have a decreased efficacy. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Overactive bladder syndrome ( OAB) is a highly prevalent medical condition, which is linked to the urodynamic observation of detrusor overactivity ( DO). Urodynamics detect DO in about half of female patients with OAB., Our study detects significant differences between female patients with OAB with and without DO. DO could be considered as a more severe form in the wide OAB spectrum and the two terms should not be used interchangeably. The detected differences should be taken into account in the design of studies for the assessment of new selective or combination treatments of OAB and in the provision of treatment in everyday clinical practice., Objective To determine if there are differences between female patients complaining of symptoms of overactive bladder ( OAB) with and without detrusor overactivity ( DO)., Patients and Methods The present study was a cross-sectional study of consecutive women attending a one-stop urodynamic assessment clinic with OAB symptoms., The King's Health Questionnaire ( KHQ) and a 3-day bladder diary incorporating the Patient's Perception of Intensity of Urgency Scale ( PPIUS) were used to assess symptoms and health-related quality of life ( HRQoL)., The participants underwent multichannel urodynamics ( UDS) according to the International Continence Society ( ICS) recommendations., Patients whose symptom of urgency was not reproduced during the laboratory test underwent a 4-h ambulatory UDS test., Results Of the 556 patients who were included in the study, 43% were diagnosed with DO by either laboratory (227/556) or ambulatory UDS (11/39)., There was no difference between the groups in age, body mass index ( BMI), menopausal status or the presence of prolapse., Patients with DO had a smaller functional bladder capacity ( P < 0.001), higher urgency episode frequency ( P < 0.001) and larger maximum and mean urge ratings ( P < 0.001)., No significant differences were found in daytime or nocturnal micturitions between the groups., The presence of DO had a more negative impact on the quality of life, with a statistically significant difference between the groups in six of the domains of the KHQ., Conclusions The present study detects objective and subjective differences between female patients with OAB with and without DO., Women with DO experience more significant impairment to their quality of life and have a greater degree of bladder dysfunction. [ABSTRACT FROM AUTHOR]

The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ-specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug-delivery. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To carry out a large-scale retrospective review of patients who had undergone surgical repair of obstetric fistula in Kenya to determine patient characteristics and determinants of successful surgical repair. Methods: The patient records of 483 surgical repairs of obstetric fistula treated by a single surgeon (H.M.) between January 2005 and July 2010 at 3 medical centers in western Kenya were retrospectively reviewed. Descriptive and bivariate statistical analyses were performed. Results: Young women with some primary or no education and prolonged labor at the time of first delivery were most highly correlated with obstetric fistula formation. Success of fistula closure was 86% for first-time vesicovaginal fistula (VVF) repairs and 67% for first-time VVF combined with rectovaginal fistula (RVF) repairs. Among women who had previously attempted VVF or combined VVF/RVF repairs, 73% and 50% of fistulas, respectively, were repaired successfully. First-time repair was significantly associated with surgical success compared with patients with a history of previous repair attempts (P =0.027). Conclusion: Among Kenyan women presenting for fistula repair, fistula most was most highly correlated with a low level of education and prolonged labor. The findings are consistent with results reported from other countries in Sub-Saharan Africa. [Copyright &y& Elsevier]

Botulinum toxin has been recently accepted as a novel treatment for lower urinary tract dysfunctions refractory to conventional treatment. Review of the clinical trials in recent years, botulinum toxin type A has been widely used in the urethra or urinary bladder to treat voiding dysfunction due to detrusor sphincter dyssynergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders such as bladder hypersensitivity, overactive bladder, and interstitial cystitis/painful bladder syndrome. Intravesical botulinum toxin type A injection is effective in treatment of urinary incontinence due to detrusor overactivity in men and women, as well as in children. Currently botulinum toxin type A has also been applied to treat lower urinary tract symptoms due to benign prostatic hyperplasia in patients not suitable for surgery. This article reviewed the recent advances of botulinum toxin type A on lower urinary tract dysfunction. [ABSTRACT FROM AUTHOR]

Recent studies suggest that antimuscarinics might suppress bladder afferent activity by blocking muscarinic receptors in the urothelium, myofibroblasts and detrusor, thereby improving overactive bladder symptoms. β3-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β3-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β3-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β3-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β3-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α1-Adrenoceptor antagonists (α1-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α1 A subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α1 A-adrenoceptors are additionally involved in the generation of storage symptoms. The α1 D subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α1-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α1-blockers and antimuscarinics has been recommended. Treatment with 5α-reductase inhibitor for 1 year improves urinary symptoms and flow rate by reducing prostatic volume in men with benign prostatic enlargement. A pooled analysis showed that the long-term (2 or 4 years) treatment with 5α-reductase inhibitor reduced the rate of progression to acute urinary retention and surgery. Combination therapy with 5α-reductase inhibitor and α1-blocker was shown to provide a rapid improvement in lower urinary tract symptoms, and reduce the relative risk of acute urinary retention and benign prostatic hyperplasia-related surgery. Phosphodiesterase inhibitors might target a nitric oxide-cyclic guanosine monophosphate pathway in the prostate, urethra and bladder. Phosphodiesterase-5 inhibitors (sildenafil or tadalafil) were shown to provide clinically relevant improvements in both male lower urinary tract symptoms and erectile dysfunction. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (prevalence) Level of Evidence 2b What's known on the subject? and What does the study add? Persistence with long-term medication in chronic diseases is typically low and that for overactive bladder medication is lower than average. Sub-optimal persistence is a major challenge for the successful management of overactive bladder. Using UK prescription data, persistence was generally low across the range of antimuscarinics. Patients aged 60 years and above were more likely to persist with prescribed oral antimuscarinic drugs than younger patients (40-59 years). Solifenacin was consistently associated with the highest rate of persistence compared with the other antimuscarinics included in the study OBJECTIVES To describe the level of persistence for patients receiving antimuscarinics for overactive bladder (OAB) over a 12-month period based on real prescription data from the UK., To investigate patterns of persistence with oral antimuscarinic drugs prescribed for OAB, across different age groups., PATIENTS AND METHODS UK prescription data from a longitudinal patient database were analysed retrospectively to assess persistence with darifenacin, flavoxate, oxybutynin (extended release [ER] and immediate release [IR]), propiverine, solifenacin, tolterodine (ER/IR) and trospium., Data were extracted from the medical records of >1 200 000 registered patients via general practice software, and anonymized prescription data were collated for all eligible patients with documented OAB ( n= 4833)., Data were collected on patients who started treatment between January 2007 and December 2007 and were collected up to December 2008, to allow each patient a full 12-month potential treatment period. Failure of persistence was declared after a gap of at least 1.5 times the length of the period of the most recent prescription., The analysis included only patients who were new to a course of treatment (i.e. who had not been prescribed that particular treatment or dosage for at least 6 months before the study period)., RESULTS The number of patients prescribed each antimuscarinic drug varied from 23 for darifenacin to 1758 for tolterodine ER., The longest mean persistence was reported for solifenacin (187 days versus 77−157 days for the other treatments)., At 3 months, the proportions of patients still on their original treatment were: solifenacin 58%, darifenacin 52%, tolterodine ER 47%, propiverine 47%, tolterodine IR 46%, oxybutynin ER 44%, trospium 42%, oxybutynin IR 40%, flavoxate 28%., At 12 months, the proportions of patients still on their original treatment were: solifenacin 35%, tolterodine ER 28%, propiverine 27%, oxybutynin ER 26%, trospium 26%, tolterodine IR 24%, oxybutynin IR 22%, darifenacin 17%, flavoxate 14%., In a sub-analysis stratified by age, patients aged ≥60 years were more likely to persist with prescribed therapy over the 12-month period than those aged <60 years., CONCLUSIONS Twelve months after the initial prescription, persistence rates with pharmacotherapy in the context of OAB are generally low., Solifenacin was associated with higher levels of persistence compared with other prescribed antimuscarinic agents., Older people are more likely than younger patients to persist with prescribed therapy. Further studies are required to understand this finding and why patients are more likely to persist with one drug rather than another. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Urothelium emerged as a crucial integrator of sensory inputs and outputs in the bladder wall, and urothelial G-protein-coupled receptors (GPCRs) may represent plausible targets for treatment of various bladder pathologies. Urothelial cell lines provide a useful tool to study urothelial receptor function, but their validity as models for native human urothelium remains unclear. We characterize the mRNA expression of genes coding for GPCRs in human freshly isolated urothelium and compare the expression pattern with those in human urothelial cell lines. OBJECTIVES To characterize the mRNA expression pattern of genes coding for G-protein-coupled receptors (GPCRs) in human freshly isolated urothelium., To compare GPCR expression in human urothelium-derived cell lines to explore the suitability of these cell lines as model systems to study urothelial function., MATERIALS AND METHODS Native human urothelium (commercially sourced) and human urothelium-derived non-cancer (UROtsa and TERT-NHUC) and cancer (J82) cell lines were used., For mRNA expression profiling we used custom-designed real-time polymerase chain reaction array for 40 receptors and several related genes., RESULTS Native urothelium expressed a wide variety of GPCRs, including α1A, α1D and all subtypes of α2 and β adrenoceptors. In addition, M2 and M3 cholinergic muscarinic receptors, angiotensin II AT1 receptor, serotonin 5-HT2A receptor and all subtypes of bradykinin, endothelin, cannabinoid, tachykinin and sphingosine-1-phosphate receptors were detected. Nerve growth factor and both its low- and high-affinity receptors were also expressed in urothelium., In all cell lines expression of most GPCRs was markedly downregulated, with few exceptions., In UROtsa cells, but much less in other cell lines, the expression of β2 adrenoceptors, M3 muscarinic receptors, B1 and B2 bradykinin receptors, ETB endothelin receptors and several subtypes of sphingosine-1-phosphate receptors was largely retained., CONCLUSIONS Human urothelium expresses a wide range of receptors which enables sensing and integration of various extracellular signals., Human urothelium-derived cell lines, especially UROtsa cells, show comparable mRNA expression to native tissue for several physiologically relevant GPCRs, but lose expression of many other receptors., The use of cell lines as model systems of human urothelium requires careful validation of suitability for the genes of interest. [ABSTRACT FROM AUTHOR]

The author discusses the treatment of megavesica and bladder rupture in foals with surgical intervention. He mentions the difference between the two conditions and the use of either conventional surgical methods or laparoscopy. He says that in both cases, active and passive micturition is possible. He adds that fluid losses and electrolyte imbalances must be corrected before inducing anaesthesia.

Purpose: Volumetric-modulated arc therapy (VMAT) is a relatively new treatment technique in radiation therapy. A comparison study of conformal, intensity-modulated radiation therapy (IMRT) and single- and double-arc VMAT plans was undertaken to evaluate the dosimetric impact of this new technology in prostate cases. The research questions were as follows: how does VMAT dosimetry compare with IMRT and conformal plans?; does VMAT increase the volume of bowel receiving lower doses?; are one or two VMAT arcs required for standard prostate cases? Methods: Eight prostate cancer and post-prostatectomy patients were randomly selected for this study. Conformal, IMRT and single and double Arc VMAT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 75.6 Gy over a course of 42 fractions to the planning target volume (PTV). Results: The Healthy Tissue Conformity Index and the conformation number results revealed the IMRT and two VMAT techniques to have superior dosimetry to the PTV compared with the conformal plans. The maximum dose delivered to the PTV was significantly higher with the single-arc VMAT technique compared with the conformal or double-arc VMAT plans. There were no significant differences between the planning techniques for the bladder and small bowel dosimetry. However, IMRT and VMAT plans delivered less radiation to the rectum and femoral heads, and a single-arc VMAT plan was optimal for the right femoral head and the two VMAT techniques were optimal to the IMRT plans for the left femoral head. Conclusions: Single- and double-arc VMAT consistently resulted in favourable or slightly superior dosimetry when compared with static gantry IMRT for prostate cases. Both the VMAT techniques and static gantry IMRT resulted in superior critical tissue sparing when compared with conformal plans. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the safety and efficacy of once-daily trospium chloride extended release (ER) in overactive bladder syndrome (OAB) in subjects aged ⩾ 75 years. SUBJECTS AND METHODS The analysis included subjects ⩾ 75 years of age with OAB. A subgroup analysis of pooled data was performed for subjects aged ⩾ 75 years from two randomized, double-blind, multicenter studies of subjects with OAB receiving oncedaily trospium 60 mg extended release (ER) or placebo for 12 weeks, followed by 9- month open-label extension periods during which all subjects received trospium ER. A total of 143 of the 1165 subjects from two phase III registration trials who were aged ⩾ 75 years (85 trospium ER, 58 placebo; mean age 79 years and ranging up to 90 years; 73% female) were evaluated. Dual primary efficacy variables were the changes from baseline in the average number of toilet voids per day and urge urinary incontinence episodes per day. RESULTS At week 12 of the double-blind period, trospium ER produced greater improvements from baseline than placebo in voiding diary parameters, OAB Patient Global Assessment, and quality of life. Efficacy and tolerability persisted among subjects receiving open-label trospium ER for up to 1 year. CONCLUSIONS Once-daily trospium chloride 60 mg ER demonstrated efficacy vs placebo and was tolerated in subjects aged ⩾ 75 years with OAB. For subjects who continued into the open-label treatment period, efficacy and tolerability were observed for up to 1 year. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation. PATIENTS AND METHODS Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12. RESULTS Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinaryincontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P < 0.05) compared to subjects who did not opt for dose escalation (non-escalators). There was no significant difference in the percentage of escalators (51%) and non-escalators (48%) who reported at least one UUI episode on baseline diary. At week 4 (before the decision to escalate was made), all outcomes were significantly improved vs baseline among both groups (all P < 0.0001), although non-escalators had significantly greater improvements in all diary variables and in PPBC and UPS scores than escalators (all P < 0.05), and the 5-day diary-dry rate (i.e. the percentage of subjects with at least one UUI episode on baseline diary and no UUI episodes on week 4 diary) was significantly higher ( P = 0.0016) among non-escalators (62%) than among escalators (42%). At week 12, all outcomes were again significantly improved vs baseline among both groups (all P < 0.0001). There were no significant differences between non-escalators and escalators in week 12 improvements for most diary variables, UPS scores, OAB-q Symptom Bother scores, the diary-dry rate (68% vs 60%) or the percentage of subjects who reported treatment satisfaction (82% vs 78%). However, escalators still had significantly greater improvements from baseline in urgency episodes, PPBC scores and OAB-q total HRQL and Coping domains ( P < 0.05). Adverse event rates were similar between non-escalators and escalators. Dry mouth was the most frequently reported adverse event; most cases were mild. CONCLUSION Flexible-dose fesoterodine significantly improved OAB symptoms and patientreported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and nonescalator groups. These results may help clinicians to identify patients more likely to require fesoterodine 8 mg to achieve maximum relief of OAB symptoms and thus facilitate dose escalation in these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the onset of efficacy of fesoterodine 4 mg once daily on overactive bladder (OAB) symptoms after 1 week of treatment. PATIENTS AND METHODS This was a prespecified analysis of data collected during the first week of a 12-week, open-label, single-arm, flexible-dose study of fesoterodine. Eligible subjects were adult men and women (aged ⩾ 18 years) who reported urinary frequency (eight or more micturitions per 24 h) and urgency (three or more episodes per 24 h) in 5-day bladder diaries at baseline, and dissatisfaction with previous tolterodine or tolterodine extended-release treatment received within 2 years of screening. All subjects received fesoterodine 4 mg once daily during the first 4 weeks of treatment (with an optional dose increase to fesoterodine 8 mg after week 4). Early onset of efficacy of fesoterodine 4 mg was assessed based on changes from baseline to week 1 in variables recorded in 5-day bladder diaries, including total micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes and nocturnal micturitions. Urgency and severe urgency episodes were defined as those rated ⩾ 3 and ⩾ 4, respectively, on the fivepoint Urinary Sensation Scale (USS) (1 = no urgency, 5 = UUI); frequency-urgency sum (a combined measure of micturition frequency and urgency) was defined as the sum of all USS ratings. RESULTS All bladder diary variables, including total and nocturnal micturitions, UUI episodes, urgency episodes, severe urgency episodes and frequency-urgency sum per 24 h, were significantly improved (all P < 0.0001) after 1 week of treatment with fesoterodine 4 mg compared to baseline. The diary-dry rate at week 1 (i.e. subjects with at least one UUI episode at baseline who subsequently reported no UUI episodes on week 1 diary) was 38%. CONCLUSION In this open-label study of subjects with OAB who had been previously treated and dissatisfied with tolterodine, fesoterodine 4 mg showed a rapid onset of efficacy at 1 week. [ABSTRACT FROM AUTHOR]

β₃-Adrenoceptor mRNA is expressed in the human heart, but corresponding receptor protein has not yet consistently been demonstrated. Furthermore, their physiological role remains highly controversial. For example, in human atria these receptors apparently do not promote cAMP formation. Evidence presented in this issue of the BJP suggests that a previously reported β₃-adrenoceptor-mediated stimulation of Ca(2+) channels at room temperature is absent at physiological temperatures, and that β₃-adrenoceptors have no effect on atrial contraction. Drugs classified as β₃-adrenoceptor agonists cause contraction in human atria but in most cases this involves β₁- and/or β₂-adrenoceptors. In contrast, in human ventricles β₃-adrenoceptor agonists can exhibit negative inotropic effects, potentially involving Pertussis toxin-sensitive G-proteins and activation of a NO synthase. However, firmer pharmacological evidence is required that these effects indeed occur via β₃-adrenoceptors. Whether the expected future use of β₃-adrenoceptor agonists in the treatment of urinary bladder dysfunction is associated with adverse events related to cardiac function remains to be determined from clinical studies. [ABSTRACT FROM AUTHOR]

Bladder rupture in a fetus is a rare occurrence. We report the first neonatal case of laparoscopic repair for prenatally diagnosed bladder rupture. A male neonate, who had presented with megacystis, bilateral hydronephrosis and hydroureters since 27 weeks-of-gestation, was delivered by emergency cesarean section because of sudden collapse of the bladder with massive ascites at 37 weeks-of-gestation. The diagnosis of bladder rupture was made by retrograde urethrocystography. Laparoscopic repair was carried out subsequent to urethral catheterization. Intraoperatively, laceration from the left side of the bladder dome to the posterior wall was observed. This tear was successfully repaired using a two-layer interrupted suture without any postoperative complications. Laparoscopic repair could be the treatment of choice for bladder rupture, because it has the advantage of closure of the perforated site more certainly than bladder decompression alone, and with better cosmesis than open repair. [ABSTRACT FROM AUTHOR]

Several studies show promising results in terms of both clinical and urodynamic improvements, supporting the efficacy, safety and tolerability of botulinum toxin serotype A (BoNT-A) for managing neurogenic detrusor overactivity (DO). DO due to spinal cord injuries represents the most frequently treated dysfunction, where the efficacy appears to be high, with beneficial effects on quality of life. Data on the management of DO in patients with multiple sclerosis, cerebrovascular accidents and Parkinson’s disease are scarce or absent; thus, the suitability of BoNT-A in the treatment neurogenic DO of other diseases of central nervous origin requires further investigation. Indeed, good quality, randomized controlled trials are still needed to identify not only the most appropriate patients to treat, but also the appropriate dose, administration technique, frequency of treatment and any eventual long-term complications. Thus, the use of intravesical BoNT-A in the control of neurogenic DO appears to be promising, but the drug is still in phase 3 clinical development, and further high-quality research is essential. [ABSTRACT FROM AUTHOR]

Urinary retention is one of a multitude of autonomic deficits resulting from acute botulism (oral botulinum intoxication). The powerful influence of botulinum-A neurotoxin (BoNT-A) on autonomic function has now been harnessed to the benefit of patients with detrusor overactivity (DO), by injecting the agent intramurally, with consequent improvement in urodynamic and clinical variables. Nonetheless, the complexity of bladder cellular physiology and putative mechanisms underlying the pathophysiological basis of DO even now render the precise mechanisms of clinical response to intravesical BoNT-A uncertain. In this review, the processes by which BoNT-A affects nerve function and the state-of-the-art in the physiological understanding of bladder dysfunction are discussed together, conveying how much must be reckoned when attempting to understand the mechanisms by which this powerful agent can improve refractory and bothersome DO. [ABSTRACT FROM AUTHOR]

The article provides a summary of developments in pharmacological therapy for the overactive bladder (OAB), particularly with regards to available antimuscarinic drugs and the newer non-anticholinergic drugs. Antimuscarinic drugs include tolterodine, trospium, darifenacin and solifenacin. Other types of drugs are those acting on membrane channels, those with mixed actions, adrenoceptors, antidepressants, prostaglandin synthesis inhibitors and vasopressin analogues.

An international group of authors present a pooled analysis of data from their phase III multicentre double-blind clinical trials in patients with overactive bladder, which evaluated the efficacy, tolerability and safety of darifenacin. They found the drug, a muscarinic M3 selective receptor antagonist, to be effective in the treatment of this condition, with excellent tolerability and safety. A paper from Denmark compares the efficacy and safety of alfuzosin and tamsulosin in a large randomized, double-blind, placebo-controlled, multicentre study. There were similar improvements in urinary symptoms and maximum urinary flow with the two drugs compared to placebo, but the incidence of sexual function adverse events was higher with tamsulosin than placebo. To evaluate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), from an analysis of pooled data from three phase III, multicentre, double-blind clinical trials in patients with overactive bladder (OAB). After a 4-week washout/run-in period, 1059 adults (85% women) with symptoms of OAB (frequency and urgency with urge incontinence) for≥ 6 months were randomized to once-daily oral treatment with darifenacin (7.5 mg, 337; or 15 mg, 334) or matching placebo (388) for 12 weeks. Efficacy was evaluated using electronic patient diaries that recorded incontinence episodes (including those resulting in a change of clothing or pads), frequency and severity of urgency, voiding frequency, and bladder capacity (volume voided). Safety was evaluated by analysis of adverse events (AEs), withdrawal rates and laboratory tests. Relative to baseline, 12 weeks of treatment with darifenacin resulted in a significant reduction in the median (% change, interquartile range) number of incontinence episodes per week; 7.5 mg (−8.8,−68.4%,−15.1 to−4.4); 15 mg; (−10.6,−76.8%,−17.3 to−5.8: both P < 0.01 vs placebo). There was a significant dose–response trend in each study for which darifenacin 7.5 and 15 mg were evaluated ( P < 0.01). There were also significant decreases in the frequency and severity of urgency, voiding frequency, and number of significant leaks (incontinence episodes resulting in a change of clothing or pads; both P ≤ 0.001 vs placebo), together with an increase in bladder capacity (both P < 0.01 vs placebo). Darifenacin was well tolerated; the most common AEs were dry mouth and constipation, although together these resulted in few discontinuations (darifenacin 7.5 mg 0.6% of patients; 15 mg 2.1%; placebo 0.3%). The incidence of peripheral/central nervous system and cardiovascular AEs were comparable with those on placebo. Darifenacin (7.5 and 15 mg once daily) is effective in the treatment of patients with OAB. As predicted by its M3 selectivity and associated M1/M2-sparing profile, darifenacin was well tolerated with no central nervous system or cardiovascular safety concerns. [ABSTRACT FROM AUTHOR]

To test the hypothesis, in a prospective randomized double-blind study, that the combination of intravesical prostaglandin E2 (PGE2) and oral bethanechol chloride (BC) are additive or synergistic in improving bladder emptying, as they have been used alone for treating impaired detrusor contractility with little clinical benefit. Nineteen patients with detrusor underactivity (17 men and two women) were eligible and randomized to one of two treatments. All had postvoid residual urine volumes (PVR) consistently of > 300 mL, most being reliant on clean intermittent self-catheterization (CISC). The experimental treatment group (nine patients) received once-weekly intravesical PGE2 (1.5 mg in 20 mL 0.9% saline) plus BC 50 mg four times daily, for a total of 6 weeks. The second group of 10 patients received a once-weekly instillation of saline together with placebo tablets, again for 6 weeks. Before treatment the median (interquartile range) PVR was 426 (405–480) mL for those receiving both drugs; this decreased to 325 (290–352) mL after completing the treatment ( P < 0.015). In the placebo group the respective values were 576 (539–777) and 538 (350–775) mL ( P = 0.09). Four of the patients receiving the active combination reported symptomatic improvement and were able to reduce the frequency of CISC. Although there was evidence of a pharmacological effect, BC and PGE2 had a limited therapeutic effect compared with placebo. Whilst we would not recommend this treatment as routine, it may be considered for the occasional treatment of a patient with detrusor underactivity. [ABSTRACT FROM AUTHOR]

Objective To evaluate histopathologically the ingrowth of urothelium over a demucosalized gastric flap used for augmentation, as such flaps increase the capacity of the bladder if the urothelium can cover the seromuscular patch. Materials and methods The study included eight male dogs; the urinary bladder was widely divided at its dome anteroposteriorly to receive a seromuscular gastric flap, sutured to the edges of the urinary bladder. Before and 1 month after surgery the changes in bladder capacity and pressure were recorded, and urothelial ingrowth assessed histopathologically. Results Two of the eight dogs died; the increase in mean bladder capacity in the remaining dogs was 20% and the decrease in mean intravesical pressure 34%. Gross pathological examination of the urinary bladder showed good ‘take’ of the gastric flap by the urinary bladder. Histopathologically, there was good healing of the flap, active ingrowth of urothelium, and no mucosal re-growth. Conclusion Bladder augmentation with a demucosalized gastrocystoplasty allows the creation of a large compliant urinary bladder with few complications caused by the incorporation of the enteric or gastric epithelium into the urinary bladder. The stomach has a rich blood supply, allowing the harvesting of a well-vascularized flap, and urothelial ingrowth over this flap in the present study was significant. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (≥65) and younger (<65) patients. DESIGN: A 12-week double-blind, placebo-controlled clinical trial. SETTING: An international study conducted at 167 medical centers. PARTICIPANTS: One thousand fifteen patients (43.1% aged ≥65) with urge incontinence and urinary frequency. INTERVENTION: Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks. MEASUREMENTS: 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. RESULTS: 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%, ≥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%;... [ABSTRACT FROM AUTHOR]

Examines the effectivity of oral cimetidine for giving relief to bladder disease. Development of the drug; Similarity between peptic ulcer disease and interstitial cystitis (IC); Evidence suggesting bladder infection involved in the case of IC.

Objective To determine the safety, efficacy and pharmacokinetics of tolterodine in children with an overactive bladder. Patients and methods 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. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Objective: To review previous reports and our experience in assessing the risk of prosthetic infections in patients undergoing bladder augmentation simultaneously with artificial genitourinary sphincter (AGUS) implantation, and in patients with in situ ventriculoperitoneal (VP) shunts, implicated as a cause of shunt infection. Patients and methods: The literature was searched to identify the number of prosthetic infections (AGUS or VP shunt) reported in patients who have undergone bladder augmentation. Additionally, the records of 53 myelodysplastic patients at our institution who had undergone bladder augmentation were reviewed to determine the incidence of AGUS and/or VP shunt infections. An AGUS was placed in 17 of these patients, who were then divided into three groups based upon the timing of their AGUS placement relative to bladder augmentation. Of the 53 patients, 47 had an in situ VP shunt at the time of their augmentation. All patients were followed for at least 12 months. Results: The reported rate of AGUS infection at the time of simultaneous bladder augmentation was not significantly different from that when these procedures were staged. In the present series, the AGUS became infected in two patients (12%); one infection occurred in each of 10 patients undergoing simultaneous procedures (10%) and one developed in each of the seven patients undergoing staged procedures (14%). Although VP shunt infections have been reported after bladder augmentation, none of the present patients had a VP shunt infection after bladder augmentation. Conclusion: These results suggest that bladder augmentation is not associated with an increased risk of prosthetic infection in patients undergoing simultaneous placement of an artificial sphincter or in those who have an in situ VP shunt. [ABSTRACT FROM AUTHOR]

Examines the role of muscarinic receptor antagonist in the treatment of the overactive bladder. Improvement of the micturition diary variables; Reduction of the incontinence episodes; Assessment of the bladder symptoms.

Investigates the laparoscopic management of bladder endometriosis. Treatment of patients with bladder endometriosis by performing a laparoscopic partial cystectomy; Disappearance of the urinary symptoms; Absence of the functional urological symptoms.

Objective To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. Patients and methods 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 (≥8 micturitions/24 h) and symptoms of urgency and/or urge incontinence (≥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. Results 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,... [ABSTRACT FROM AUTHOR]

The paper presents a case of a boy born with a bladder exstrophy, who underwent several surgical procedures, including bladder augmentation. During the last procedure, the patient received a suprapubic catheter that accidentally slipped out. The epithelized neobladder-cutaneous fistula resulted in a continent and easily catheterizable abdominal stoma. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on the study regarding the use of interferential electrical stimulation (IFES) in treating non-neuropathic underactive bladder in children. Topics discussed include the improvement in enuretic episodes with the use of urotherapy, the improvement in urinary tract infection (UTI) and incontinence in IFES, and the improvement in gastrointestinal function.

The article discusses findings of a research showing Transient receptor potential cation channel subfamily M member 8 (TRPM8) antagonising in treating lower urinary tract symptoms. Topics include TRPM8 decreasing the micturition initiation threshold, increasing the activity of TRPM8 by cold temperatures, and cooling chemicals including menthol and icilin, and recent studies showing importance of TRPM8 in bladder hypersensitivity disorders.

An introduction is presented in which the editor discusses articles in the issue on topics including immunological tolerance in kidney transplantation, bladder preservation therapy, and safety and use of high-dose mizoribine combination therapy.