Distribution and sub-types of afferent fibre in the mouse urinary bladder.

AIM: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences. MATERIALS AND METHODS: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry. Cryostat sections were cut and stained for Protein Gene Product 9.5 (PGP), calcitonin gene related polypeptide (CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS). RESULTS: In the sub-urothelium, different types of afferent nerve fibre were found, i.e. immunoreactive (IR) to; CGRP, NF, VAChT, and/or nNOS. At the bladder base, the sub-urothelium was more densely innervated by CGRP-IR and VAChT-IR nerve fibres, then at the lateral wall. NF- and nNOS nerves were sparsely distributed in the sub-urothelium throughout the bladder. At the lateral wall the inner muscle is densely innervated by CGRP-IR nerve fibres. NF, VAChT and nNOS nerves were evenly distributed in the different muscle layers throughout the bladder. Nerve fibre terminals expressing CGRP and NF were found within the extra-mural ganglia at the bladder base. CONCLUSIONS: Different types of afferent nerve fibres were identified in the sub-urothelium of the mouse bladder. At the bladder base the sub-urothelium is more densely innervated than the lateral wall by CGRP-IR and VAChT-IR afferent nerve fibres. CGRP and NF afferent nerve fibres in the muscle layer probably relay afferent input to external ganglia located near the bladder base. The identification of different afferent nerves in the sub-urothelium suggests a functional heterogeneity of the afferent nerve fibres in the urinary bladder.

Urogenital and Sexual Complaints in Female Club Cyclists-A Cross-Sectional Study.

INTRODUCTION: Cycling has gained increased popularity among women, but in contrast to men, literature on urogenital overuse injuries and sexual dysfunctions is scarce. AIM: To determine the prevalence and duration of urogenital overuse injuries and sexual dysfunctions in female cyclists of the largest female cycling association in The Netherlands. METHODS: A cross-sectional questionnaire survey was sent to 350 members of the largest female Dutch cycling association and 350 female members of a Dutch athletics association (runners). MAIN OUTCOME MEASURES: The prevalence and duration of urogenital overuse injuries and sexual complaints were assessed using predefined international definitions. RESULTS: Questionnaire results of 114 cyclists (32.6%) and 33 runners (9.4%) were analyzed. After at least 2 hours of cycling, dysuria, stranguria, genital numbness, and vulvar discomfort were present in 8.8%, 22.2%, 34.9%, and 40.0%, respectively (maximum duration 48 hours). These complaints are not present in the controls (P < .001). In multivariable logistic regression analysis, increased saddle width was significantly associated with the presence of dysuria and stranguria. Older age was significantly associated to the presence of vulvar discomfort. Of the cyclists, 50.9% has at least one urogenital overuse injury. Insertional dyspareunia was present in 40.0% of cyclists and lasted until 48 hours after the effort. The latter complaint was not present in runners (P < .001). Uni- or bilateral vulvar edema was reported by 35.1% of cyclists. As for general complaints, 18.4% of cyclists reported a change in sexual sensations and 12.8% reported difficulties in reaching orgasm owing to cycling-related complaints. Limitations include population size and the use of non-validated questionnaires. CONCLUSIONS: The results of this study suggest that urogenital overuse injuries and sexual complaints are highly prevalent in female cyclists who are active participants in riding groups.

Phosphodiesterase type 2 distribution in the guinea pig urinary bladder.

INTRODUCTION: Nitric oxide-stimulated cGMP synthesis represents an important signalling pathway in the urinary bladder. Inhibitors of the PDE1 and PDE5 enzyme have been studied to treat storage and voiding disorders in clinical settings. The distribution of PDE2 in the bladder is unknown. This study focuses on the distribution and site of action of PDE2 within the guinea pig urinary bladder wall. METHODS: Six male guinea pig bladders were dissected and treated in 2 ml Krebs' solution and 10 µM of the specific PDE2 inhibitor, Bay 60-7550 at 36 °C for 30 min. After stimulating tissues with 100 µM of diethylamine-NONOate for 10 min, the tissues were snap frozen and cut in 10 µm sections which were examined for cGMP immune-reactivity, co-stained with either vimentin, synaptic vesicle protein 2, calcitonin gene-related protein and protein gene product 9.5. RESULTS: PDE2 inhibitor Bay 60-7550 inhibits cGMP breakdown the most in the urothelial and suburothelial layers, as well as on the nerve fibres. After inhibition by Bay 60-7550, cGMP was mainly expressed in the intermuscle interstitial cells and the nerve fibres of the outer muscle layers of lateral wall, indicating the presence of PDE2 activity. DISCUSSION AND CONCLUSION: Our study is the first to show the distribution of PDE2 in the bladder which was shown to be present in the urothelium, mainly umbrella cells, the interstitial cells of the suburothelium and the outer muscle, as well as in nerve fibres.

Effects of Macroplastique Implantation System for stress urinary incontinence and urethral hypermobility in women.

A study was carried out to evaluate efficacy of Macroplastique(R) (MPQ) Implantation System (MIS) in women with urodynamic stress urinary incontinence (SUI) and urethral hypermobility after an unsuccessful conservative treatment. This is a prospective randomized controlled trial in women without previous incontinence surgery. Twenty-four women received MPQ. Twenty-one controls underwent a pelvic floor muscle exercises home program. Follow-up was at 3 months and the MPQ group also at 12 months. At 3 months, pad usage decreased significantly more in the MPQ group than in the control group (p = 0.015). According to physician and patient self-assessment, respectively, 71% and 63% women in the MPQ group were considered cured or markedly improved. This was significantly higher compared to controls. There was a significant higher increase of Incontinence Quality-of-Life questionnaire score in the MPQ group compared to controls (p = 0.017). Improvements in MPQ group at 3 months are sustained to 12 months. Adverse events were mild and transient. MIS is an acceptable option for women with SUI and urethral hypermobility.

Long term results of neuromodulation by sacral nerve stimulation for lower urinary tract symptoms: a retrospective single center study.

OBJECTIVE: To analyse the influence of technical improvements of Sacral Nerve Stimulation (SNS) on the incidence of surgical interventions and subjective long-term results of SNS. METHODS: Retrospective, transversal study analyzing records of implanted patients at our department of Urology. RESULTS: Of 149 patients analyzed, 107 had overactive bladder symptoms and 42 had urinary retention. Mean follow-up was 64,2 (sd = 38,5) months. In the whole group 194 adverse events occurred. 6 Patients had infection in their implanted system, one was explanted for infection. Most events could be solved by giving advice or by reprogramming the stimulator. 129 reoperations have been performed and 21 patients had their system explanted. Analysis of the data shows a striking difference in the incidence of reoperations, but small differences in subjective results in the groups of patients implanted before or after 1996, suggesting that a proactive approach towards adverse events is worthwhile. CONCLUSIONS: SNS gives lasting benefit in patients with refractory symptoms of overactive bladder and non-obstructive urinary retention. The differences in outcomes and incidence of reoperation can be attributed to the learning curve and technical and surgical improvements in the application of SNS.

Sacral nerve stimulation for refractory urge symptoms in elderly patients.

OBJECTIVE: The presence of an overactive detrusor (OD) is becoming more prevalent in the elderly and may severely influence the social life and activities of daily living in the senior, otherwise healthy, person. There is a marked age-dependent increase in OD above the age of 65 years, which is mainly attributed to dysfunction, with loss of voluntary control, of the micturition reflex and decreased perception of bladder fullness. MATERIAL AND METHODS: Herein, we evaluate the outcome of sacral nerve stimulation in five patients aged >65 years derived from a large, multinational, randomized, prospective study. RESULTS: The effect on symptoms was excellent in two subjects. There was a moderate improvement in another subject and a variable but eventually small effect in the remaining two patients. The results appeared to be more favourable in younger patients. CONCLUSION: Our findings suggest that the outcome of sacral nerve stimulation is more unpredictable in the elderly, a fact that should be considered when counselling the patient. However, it should be remembered that, even for the older, active person, urge incontinence may have a severe impact on quality of life and that the majority of patients treated with an implant will benefit from this treatment.

Systematic review: efficacy of silicone microimplants (Macroplastique) therapy for stress urinary incontinence in adult women.

OBJECTIVE: To assess the efficacy of silicone microimplants (Macroplastique; polydimethylsiloxane) therapy for stress urinary incontinence in adult women, using a systematic review of identified studies. MATERIALS AND METHODS: A computer-aided and manual search for published studies investigating silicone microimplants therapy for stress urinary incontinence in adult women. The methodological quality of the included studies was assessed using criteria based on generally accepted principles of interventional research. RESULTS: Only two RCTs, only published as an abstract, were found. Eleven pre-experimental or observational studies were identified. Overall, the methodological quality was low. The main methodological shortcomings of the studies were: no random allocation procedure, lack of prestratification on prognostic determinants, no blinding, small sample sizes, and lack of proper analysis and presentation of results. There was variability in the indication for implantation, implantation procedure, rate and volume of silicone microimplants. The use of different outcome measures in most of the trials made comparison between studies difficult. CONCLUSIONS: Because of the low methodological quality of included studies, results should be interpreted with caution and no firm conclusions about the efficacy of silicone microimplants were possible. Randomized clinical trials, using valid and reliable subjective and objective measurements, are necessary to establish the efficacy of silicone microimplants therapy in treating stress urinary incontinence in adult women.

Quality of life, functional outcome and durability of the AMS 800 artificial urinary sphincter in patients with intrinsic sphincter deficiency.

OBJECTIVE: To evaluate the quality of life, functional outcome and durability of the AMS 800 artificial urinary sphincter (AUS) in patients with urinary incontinence due to intrinsic sphincter deficiency of mixed origin. PATIENTS AND METHODS: Between 1991 and 2000, 34 AUS were implanted in 31 patients (24 males/7 females) with mean age of 59 (range 15-75) years. Using a questionnaire, patients' urinary function and quality of life were assessed in 22 patients with an AUS in situ. To evaluate efficacy and durability of the device, the primary adequate function (P-AF) and additional procedure-assisted adequate function (APA-AF) rates were determined on the basis of a Kaplan-Meier survival analysis. RESULTS: The social continence rate (0-1 pads/24 h) was 55% with a mean follow-up of 46 months. The revision rate was 26% and the explantation rate 35%. The 5-year P-AF and APA-AF rates were 41 and 44%, respectively. The pad score decreased from 2.95 to 1.23 after AUS implantation (p < 0.0001) leading to a high mean patient satisfaction (rated as 4.0 on a visual analog scale of 0-5). Twenty-one patients (95%) would undergo the procedure again under the same circumstances. Patients with previous anti-incontinence procedures showed a significantly higher explantation rate (p = 0.004). CONCLUSION: In spite of a relatively high re-operation rate and moderate social continence state, patient satisfaction was found to be great mainly due to the relative improvement in incontinence. The AMS 800 AUS is a reliable device with few mechanical complications. Extensive preoperative counseling is mandatory.

Urodynamic results of sacral neuromodulation correlate with subjective improvement in patients with an overactive bladder.

OBJECTIVES: Standard urodynamic investigations showed no correlation between the efficacy of sacral neuromodulation (SNS) and urodynamic data. Ambulant urodynamic investigations (ACM) are presented as more sensitive and reliable in detecting and quantifying bladder overactivity. In this study we looked at the correlation and results of ambulant urodynamic data and the clinical effects of SNS. METHODS: Data of patients with bladder overactivity, who underwent an ACM before and during SNS were investigated. Blind analyses of the ACM were performed and the detrusor activity index (DAI) was calculated as the degree of bladder overactivity of the detrusor. The ACM parameters, before and during SNS, were analyzed and correlated to the clinical effect of SNS. RESULTS: In 22 of the 34 patients a DAI before and during stimulation could be calculated because of quality aspects. In all other patients, the other ambulatory urodynamic parameters could be analyzed and a significant reduction was found in bladder overactivity. A significant correlation (p = 0.03) was found in DAI reduction of the ACM before and during SNS as compared to the clinical improvement in overactive bladder symptoms. CONCLUSIONS: The objective and subjective results show a decrease in bladder overactivity during SNS. During SNS bladder instabilities are still present, which is in accordance with the published literature. The reduction of the DAI during SNS as compared to before SNS correlates significantly to the clinical effect of SNS.

Long-term efficacy and safety results of the two-stage implantation technique in sacral neuromodulation.

OBJECTIVE: To assess the long-term efficacy and safety of two-stage sacral neuromodulation with an implantable pulse generator (IPG) in patients treated for urinary urge incontinence (UI) and/or urinary retention (UR). PATIENTS AND METHODS: The two-stage technique is used if patients have a good response during the acute phase of the percutaneous nerve evaluation (PNE) test, but have a poor response during the following 4-7 days (subchronic phase). In the first stage only the permanent electrode was implanted and connected to a temporary external stimulator, allowing patients to be assessed for longer. If the main symptoms improved by more than half the patient proceeded to the second stage, the insertion of the IPG. We reviewed all patients who underwent two-stage implantation; all had signed an informed consent and were asked to complete voiding diaries and a questionnaire to assess the subjective effects of the therapy. Safety was assessed from relevant medical events, management, and relative to the thera-py and resolution. Residual urine was assessed by self-catheterization. The long-term voiding diary results were compared with baseline estimates and analysed statistically using the two-sided Student's t-test. RESULTS: Between 1991 and 1998, 15 patients (13 women and two men, mean age 53 years, range 44-66) underwent the two-stage technique; the mean (median, range) follow-up was 4.9 (5.2, 2.5-7.5) years. Seven patients had UI and seven had UR, with one having both. The mean (range) number of PNEs undertaken in each patient was 2.1 (1-4) and these all failed in the subchronic phase. All patients underwent a first- and second-stage implant after a mean (range) screening period of 12.2 (2-29) days. One patient was explanted after implantation of only the first stage, and two others explanted in a later phase because the IPG was ineffective during the follow-up. The voiding diary results of the remaining 12 patients showed improvement in all the main variables, and in the subjective assessment 11 reported an improvement and were satisfied with the therapy. There were 17 adverse events, 14 of which were resolved and seven of which required surgical intervention. CONCLUSION: The long-term results of the two-stage implantation show clinically and statistically significant improvements, probably because the implantation of the lead (first stage) more closely resembles the final therapy. If a temporary PNE test is not optimal (lead migration, longer testing needed), the two-stage technique can offer a good and safe alternative of comparable efficacy in the long-term. If the two-stage technique had not been available to these 12 patients they would not have been offered neuromodulation.

Unilateral versus bilateral sacral neuromodulation in patients with chronic voiding dysfunction.

PURPOSE: Bilateral sacral nerve neuromodulation has been proposed as a more effective treatment for chronic voiding dysfunction. However no comparison with the unilateral approach has been performed. We investigated the possible advantage of bilateral sacral neuromodulation. MATERIALS AND METHODS: In a prospective randomized crossover trial we investigated 33 patients who underwent bilateral implantation of a temporary test lead. Unilateral and bilateral test stimulation was continued for 4 to 6 days in all patients. Patients were randomly assigned to start with bilateral or unilateral stimulation. Between the stimulation episodes a 2-day washout interval was scheduled. Voiding diaries were completed at baseline and during the entire stimulation period. Sacral x-rays were taken to confirm lead positioning or possible migration after implantation and at the end of the test stimulation period. After 10 days the temporary leads were removed and voiding diaries were analyzed. RESULTS: After stimulation sacral x-ray revealed test lead migration in 8 patients, leaving 12 patients with urge incontinence and 13 with voiding difficulty and urinary retention available for review. A statistically significant improvement in voiding parameters was seen during the test stimulation period. However no statistically significant improvement was seen due to bilateral stimulation compared to unilateral stimulation. Two patients with urinary retention only started voiding to completion during bilateral stimulation. CONCLUSIONS: Bilateral is in general not superior to unilateral sacral neuromodulation. However, in some individuals bilateral stimulation may be more effective in relieving symptoms. Therefore, if unilateral percutaneous nerve evaluation fails, a bilateral test should be considered.