Additional value of triple-sensor urethral catheter in demonstrating urethral pressure variations during filling cystometry.

AIMS: During filling cystometry, urethral pressure variations (UPV) can be observed. The clinical relevance and a clear definition of this phenomenon are still a matter of debate. For further research and definition of UPV, it is important to determine how this condition can best be demonstrated. The purpose of this study is to compare continuous urethral pressure measurements with a single urethral-sensor catheter and a triple urethral-sensor catheter in demonstrating UPV. METHODS: Seventy-five adult female patients requiring urodynamic investigation enrolled in this prospective study. All patients underwent two series of filling and voiding cystometry. One series was performed with a dual-air balloon sensor urodynamic catheter, the other series with a triple urethral-sensor catheter. UPV were defined as urethral pressure drop exceeding 30 cmH2O. RESULTS: The prevalence of UPV was 37.3% (28 out of 75 patients), more common than detrusor overactivity. The triple urethral-sensor catheter was more sensitive than the single urethral-sensor catheter: In eight patients UPV were demonstrated with both catheters and in 18 patients only in the measurement with the triple urethral-sensor catheter. This difference in detection was significant (P < .001). CONCLUSION: There is an additional value in measurement with the triple urethral-sensor catheter for demonstration of UPV during filling cystometry. Currently, continuous measurement of urethral pressure during filling cystometry and UPV is not defined within International Continence Society terminology. The single urethral-sensor catheter is useful for a start, however, it demonstrates less than half of all UPV.

Bladder sensations in male and female overactive bladder patients compared to healthy volunteers: a sensation-related bladder diary evaluation.

Objectives: To investigate the differences in bladder sensations of overactive bladder (OAB) patients compared to healthy volunteers. In addition, to see if bladder sensations are different in men and women.Methods: In a prospective, longitudinal study (METC 09-2-095), 66 volunteers and 68 OAB patients were included. Anticholinergic medication was stopped. Subjects filled out a sensation-related bladder diary (SR-BD), for two periods of 3 days, including a 4-points urgency scale and visual analogue scale for perception of bladder fullness.Results: In total, 6160 voids were assessed. Patients voided more often with higher degrees of urge at a lower mean voided volume (193 vs 270 ml/void; p < 0.001) than healthy volunteers. The mean urinary frequency per litre diuresis was also higher (5.8 vs 4.1/l; p < 0.001) in patients. At the same voided volume: patients perceived a higher mean bladder fullness, independent of the degree of urge, and higher urgency (1.4 vs 0.5/100 ml; p < 0.001) than healthy volunteers. There were no gender differences in the above-mentioned voiding parameters, except for the mean voided volume at urge 3 in volunteers (340 ml in men vs 362 ml in women; p = 0.03) and urge 1 in patients (171 ml in men vs 135 ml in women; p = 0.027).Conclusions: Bladder sensations were significantly increased in everyday life for both male and female OAB patients compared to healthy volunteers. OAB patients experienced a higher mean bladder fullness sensation, independent of the degree of urge, and higher mean urge/urgency at the same voided volume than volunteers. Bladder sensations are crucial in the assessment of treatment response.

The discrepancy between European Association of Urology (EAU) guidelines and daily practice in the evaluation and management of nocturia: results of a Dutch survey.

BACKGROUND AND OBJECTIVE: In addition to the evaluation of voiding symptoms, in the evaluation of patients with nocturia, one should also consider other related causes such as sleep disorders, obstructive sleep apnoea (OSAS), diabetes and heart failure. In this study, we have aimed to assess the current knowledge and implementation of the EAU guidelines regarding nocturia in common urological practice in the Netherlands. SETTING AND PARTICIPANTS: In a national cross-sectional survey distributed among 450 urologists and urology residents in the Netherlands, the implementation of the recommendations of the European Association of Urology (EAU) guidelines on nocturia evaluation and management was studied. RESULTS AND LIMITATIONS: This survey revealed that only some aspects of the EAU guidelines are applied in the daily clinical practice and that some important parts are not. For example, only a minority asks about alcohol consumption and symptoms suggestive for diabetes or OSAS. In addition, a majority reported to use a bladder diary for 1-3 days instead of for a minimum of 3 days as recommended by the EAU guidelines. In the management of nocturia, a trial of timed diuretic therapy is only reported by a minority, whereas the use of beta-3 antagonists, which is not mentioned in the guidelines, is applied by a large majority. Desmopressin recommended for nocturnal polyuria is prescribed by two-third of Dutch urologists. CONCLUSIONS: These observations mandate better education and campaigns to raise the awareness on the EAU-guideline recommendations for nocturia.

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.

Prevalence and triage of first contact pelvic floor dysfunction complaints in male patients referred to a Pelvic Care Centre.

AIMS: (i) To describe and analyse pelvic floor dysfunction symptoms in men referred to a Pelvic Care Centre (PCC). (ii) To describe the triage process of the same patients based on response to a first-contact interview. METHODS: Triage started with a telephone interview using previously constructed questions, asking for six types of PF complaints during the preceding 6 months. If present, complaint severity was registered on a 0-10 scale. Next, these first-contact complaints were used to describe patient case mix profiles using cross-tabular analysis. Later on, at first PCC visit, an intake questionnaire regarding specific PF health problem(s) was filled out. This procedure contributed to a firm baseline characterization of the individual patient profile and a clinically valid allocation to structured, predefined assessment and treatment. RESULTS: From 2005 to 2013 985 first-time patients (mean age 58.2 years (SD 15.3) have been referred to the PCC. Most frequently mentioned complaints: voiding dysfunctions (73.9%), urinary incontinence (29.5%), sexual problems (16.6%), faecal incontinence (13.9%), constipation (9.6%), and prolapse (0.3%). A first appointment to a single specialist was determined in 805 (81.7%) patients, in 137 (13.9%) consultation of >1 specialist. Data analysis revealed higher-order interactions between PF complaints, suggesting patient profile complexity and patient population heterogeneity. CONCLUSIONS: One out of seven PCC patients showed multifactorial problems, needing >1 specialist. PF complaints either turned out to stand alone or cluster with others, or even to strengthen, weaken, nullify or inverse relationships. Neurourol. Urodynam. 35:487-491, 2016. © 2015 Wiley Periodicals, Inc.

Prevalence and triage of first-contact complaints on pelvic floor dysfunctions in female patients at a Pelvic Care Centre.

AIMS: (i) To describe and analyse pelvic floor dysfunction symptoms in women referred to a Pelvic Care Centre (PCC). (ii) To describe the triage process of the same patients based on response to a first-contact interview. METHODS: Triage started with a telephone interview using previously constructed questions, asking for seven types of PF complaints during the preceding 6 months. If present, complaint severity was registered on a 0-10 scale. Next, these first-contact complaints were used to describe patient case mix profiles using cross-tabular analysis. Later on, at first PCC visit, an intake questionnaire containing questions on specific PF health problem(s) was filled out. This procedure contributed to a firm baseline characterization of the individual patient profile and a clinically valid allocation to structured, predefined assessment, and treatment. RESULTS: From 2005 to 2013, 4473 first-time patients (mean age 56.9 (SD 16.2) have been referred to the PCC. Most frequently mentioned complaints: voiding dysfunction (59.5%), urinary incontinence (46.6%), prolapse (41.1%), fecal incontinence (15.1%), constipation (12.6%), and sexual problems (4.6%). A first appointment to a single specialist was determined in 3.110 (69.5%) patients, in 1.192 (26.7%) consultation of >1 specialist. Data analysis revealed higher-order interactions between PF complaints, suggesting patient profile complexity and patient population heterogeneity. CONCLUSIONS: More than one out of four PCC patients showed multifactorial problems, needing >1 specialist. PF complaints either turned out to stand alone or cluster with others, or even to strengthen, weaken, nullify, or inverse relationships. Neurourol. Urodynam. 35:503-508, 2016. © 2015 Wiley Periodicals, Inc.

Changes in voiding behavior in a mouse model of Alzheimer's disease.

Besides cognitive decline and behavioral alteration, urinary incontinence often occurs in patients suffering from Alzheimer's disease (AD). To determine whether the transgenic mouse model of AD, APP/PS1 (APP(SL)/PS1(M146L)) mouse, shows alteration of the urinary bladder function and anxiety, as for patients with AD, we examined the urinary marking behavior in relation to affective behavior. At 18 months of age voiding behavior of APP/PS1 and wild type (WT) mice was assessed by using a modified filter paper assay in combination with video tracing, with the cage divided into a center and corner zones. Anxiety-related behavior and locomotion were respectively tested in an elevated zero maze (EZM) and an open field (OF). The APP/PS1 mice urinated more in the center zone than the WT mice. The total volume of markings was significantly lower in the APP/PS1 mice. In both groups, the average volume of a marking in the corner zone was larger than in the center zone. In the EZM, the APP/PS1 mice spent less time in the open arms of the arena, considered as anxiogenic zones, than the WT mice. During the OF task, the APP/PS1 mice covered a longer distance than the WT mice. These findings show that the APP/PS1 mice have a different voiding behavior compared to the WT mice, i.e., urinating with small volumes and voiding in the center of the cage, and suggest that increased locomotor activity and anxiety-related behaviors are factors in the change in voiding pattern in the APP/PS1 mouse.

Factors impacting bladder underactivity and clinical implications.

Lower urinary tract symptoms in the voiding phase can be due to an underactive bladder, but are usually similar to symptoms of infravesical obstruction or dysfunctional voiding. The underactive bladder can be caused by an impaired detrusor contraction but also by a derangement of local and central neuro-cognitive regulatory systems or an impairment of bladder sensation. Potential risk factors of bladder underactivity include: ageing, diabetes, neurogenic disease, cardiovascular disease, obstruction and psychological causes. Comprehensive diagnostic and detection techniques for an underactive detrusor are necessary. To establish the diagnosis and follow up new treatments, useful urodynamic parameters and threshold values have to be determined. As neuro-cognitive regulation plays an important role in the control of voiding, psychological factors have to be taken into account during the assessment in these patients. Ambulatory urodynamic techniques therefore have to be considered. Voiding is determined by the balance of both the detrusor contraction and the resistance of the bladder outlet, a dysfunction in one factor can be compensated by a counter-acting function of the other factor. Therefore, to predict voiding problems in the future, it will be indicated to assess the compensatory capacity of the detrusor contractility, contractile reserve, and the outlet relaxation capacity. If novel treatments and evaluation techniques have become available, it is likely that in the future, many patients that get a TURP now, can be treated by pharmacological agents directed towards increasing the bladder contractility in a balanced combination with medication directed towards lowering the bladder outlet resistance.

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.

The use of hypochlorous acid as a model for investigating bladder overactivity.

UNLABELLED: Involuntary detrusor contractions play an important role in the development of urge incontinence. Also in an in-vitro situation contractions which develop spontaneously can be seen; a parallel with the in vivo observations is likely. In order to study this muscle overactivity we investigated the possibility to induce this phenomenon with oxidative stress using hypochlorous acid (HOCl). MATERIALS AND METHODS: Urinary bladder muscle strips from pigs were mounted in a custom made organ bath and incubated for 20 minutes in Krebs solution. Next HOCl (10 µM) was added to the organ bath and the onset of overactive contractions was closely followed. Overactivity was defined as a development of more than 5 phasic detrusor contractions per minute without any other provocation in the 30 minutes following addition of HOCl to the organ bath. RESULTS: Of the 50 strips which were used 36 (72%) became overactive after exposure to HOCl during 30 minutes recording. In 76% of the overactive strips overactivity occurred within 5 minutes, in 19% between 5 and 15 minutes, and in 5% it took longer than 15 minutes. The overactivity could be stopped by washing out HOCl for 10 minutes after which still a significant contraction after EFS and ACh stimulation was seen. CONCLUSIONS: It can be concluded that an oxidative stressor, like HOCl, is capable of inducing smooth muscle overactivity. This model can be used for the development and testing of new treatment modalities for the overactive detrusor. Furthermore, this study provides evidence for a causal relationship between oxidative stress and detrusor overactivity.

The use of Hypochlorous Acid as a Model for Investigating Bladder Overactivity

Involuntary detrusor contractions play an important role in the development of urge incontinence. Also in an in-vitro situation contractions which develop spontaneously can be seen; a parallel with the in vivo observations is likely. In order to study this muscle overactivity we investigated the possibility to induce this phenomenon with oxidative stress using hypochlorous acid (HOCl). Materials and Methods Urinary bladder muscle strips from pigs were mounted in a custom made organ bath and incubated for 20 minutes in Krebs solution. Next HOCl (10µM) was added to the organ bath and the onset of overactive contractions was closely followed. Overactivity was defined as a development of more than 5 phasic detrusor contractions per minute without any other provocation in the 30 minutes following addition of HOCl to the organ bath. Results Of the 50 strips which were used 36 (72%) became overactive after exposure to HOCl during 30 minutes recording. In 76% of the overactive strips overactivity occurred within 5 minutes, in 19% between 5 and 15 minutes, and in 5% it took longer than 15 minutes. The overactivity could be stopped by washing out HOCl for 10 minutes after which still a significant contraction after EFS and ACh stimulation was seen. Conclusions It can be concluded that an oxidative stressor, like HOCl, is capable of inducing smooth muscle overactivity. This model can be used for the development and testing of new treatment modalities for the overactive detrusor. Furthermore, this study provides evidence for a causal relationship between oxidative stress and detrusor overactivity. .

Do patients with OAB experience bladder sensations in the same way as healthy volunteers? A focus group investigation.

AIMS: To describe the terminology and pattern of bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in patients with OAB and to compare these results with a previous study conducted in healthy volunteers. METHODS: Three groups of patients with OAB, in total 10 patients, participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. During the first two sessions, participants described how they experienced their bladder sensations in daily life and during a non-invasive bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered and describing the pattern of sensations. RESULTS: Patients describe their bladder sensations as a pressure or a tingling sensation and the pattern can be described by terms ranging from no sensation to an absolute need to void. The absolute need to void may develop suddenly or more slowly progressive. The mean development of bladder sensation is significantly different between patients and healthy volunteers as well as their average diuresis. CONCLUSIONS: Patients with OAB describe their bladder sensations as a pressure or a tingling sensation. There appear to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void. Furthermore bladder sensation develops significantly different in volunteers than in OAB patients.

How should bladder sensation be measured? ICI-RS 2011.

AIMS: Disturbed bladder sensations, or in broader terms, sensory dysfunctions are increasingly recognized as key elements in the origin and manifestation of symptom syndromes of urinary dysfunction. Adequate assessment of bladder sensation is crucial to improve our understanding of the pathophysiology and treatment of urinary dysfunction. This manuscript summarizes the discussions of a think tank on "How to measure bladder sensation" held at the ICI-RS meeting in 2011. METHODS: Based upon literature reviews on bladder sensation presented at the think tank in the ICI-RS meeting, discussions evolved which were summarized in the ICI-RS report. Different physicians/researchers further elaborated on this report, which is presented in this manuscript. RESULTS: Bladder sensations are not merely the result of bladder distension. Other factors inside the bladder or bladder wall: central processing and/or cognitive manipulation may play an important role. Current methods to measure sensations such as urodynamics, voiding diaries, forced diuresis, electrical stimulation and brain imaging are likely sub-optimal as they only consider part of these factors in isolation. CONCLUSIONS: Different methods to measure bladder sensations have been described and are used in clinical practice. Current methods only address part of the parameters responsible for the generation and perception of urinary sensations. Further focused research is required, and several recommendations are provided.

How does the urothelium affect bladder function in health and disease? ICI-RS 2011.

The urothelium is a multifunctional tissue that not only acts as a barrier between the vesical contents of the lower urinary tract and the underlying tissues but also acts as a sensory organ by transducing physical and chemical stresses to the attendant afferent nervous system and underlying smooth muscle. This review will consider the nature of the stresses that the urothelium can transduce; the transmitters that mediate the transduction process; and how lower urinary pathologies, including overactive bladder syndrome, painful bladder syndrome and bacterial infections, are associated with alterations to this sensory system. In particular, the role of muscarinic receptors and the TRPV channels system will be discussed in this context. The urothelium also influences the contractile state of detrusor smooth muscle, both through modifying its contractility and the extent of spontaneous activity; potential pathways are discussed. The potential role that the urothelium may play in bladder underactivity is introduced, as well as potential biomarkers for the condition that may cross the urothelium to the urine. Finally, consideration is given to vesical administration of therapeutic agents that influence urinary tract function and how the properties of the urothelium may determine the effectiveness of this mode of delivery.

Detrusor underactivity: a plea for new approaches to a common bladder dysfunction.

AIMS: Detrusor underactivity (DU) is defined by the International Continence Society as a contraction of reduced strength and/or duration resulting in prolonged or incomplete emptying of the bladder but has yet received only little attention. The purpose of this report is to summarize the ICI-RS meeting in Bristol in 2010 exploring current knowledge on DU and outline directions for future research. METHODS: A think tank discussion was held and the summary of discussions was presented to all ICI-RS participants. This report is based on the final discussions. RESULTS: The understanding of the pathophysiology, epidemiology, assessment, and treatment of DU remains rudimentary. DU is defined by pressure-flow analysis but no consensus exists regarding which of the available formulae should be used for quantification of detrusor work. DU is likely to be multifactorial. Aging causes a decay in detrusor activity but other concomitant causes, either myogenic or neurogenic, may aggravate the problem resulting in decrease of detrusor contractility. No effective pharmacotherapy for the condition exists. Only a few surgical therapeutic strategies have been explored, such as neuromodulation and skeletal muscle myoplasties. Consequently, the management of affected individuals remains unsatisfactory. CONCLUSIONS: Future directions recommended by the ICI-RS panel include assessment of pathogenesis by developing novel animal models in addition to new non-invasive tests allowing longitudinal trials. Furthermore, optimizing the existing evaluation algorithms to support standard testing for DU and further epidemiological studies to quantify the size of the problem are required for the development of future treatment modalities.

On the nature of bladder sensation: the concept of sensory modulation.

AIMS: Going to the toilet is an essential everyday event. Normally, we do not give much thought to the sensations and factors that trigger voiding behavior: we just go. For many people, this apparently simple task is complicated and dominates their life. They have strong sensations and sudden desires to void, often resulting in incontinence. It is therefore important that we understand the origins for this functional change and identify means to alleviate it. METHODS: Literature survey. RESULTS: A considerable body of work has focused on this problem and ideas and concepts on the nature of bladder sensations are embedded in the literature. In this paper we argue the necessity to return to first principles and a re-examination of the problem. We explore the use of focus groups to identify relevant bladder sensation and what triggers 'bladder' behavior. We argue that there are differences in what can be described as 'introspective bladder sensations' and the sensations reported immediately before a void, 'void sensations'. Finally, we propose an alternative model describing how peripheral information generating 'introspective sensations' and 'void sensations' might be different but interrelated sensations. By exploring such ideas and identifying such complexity it is our intention to stimulate debate and generate further research in the field in order to understand better the physiology of bladder sensation and the pathology of increased urge, frequency and incontinence. CONCLUSIONS: Review of the literature on bladder sensation and the established ideas suggests that we might be missing something and the problem of normal and increased sensation and of urgency may be much more complex.

Changes in bladder innervation in a mouse model of Alzheimer's disease.

AIM: The aims of this study were to compare the structure of bladders from a transgenic mouse model of Alzheimer's disease with age matched control animals and to explore the idea that any structural differences might be related to functional bladder changes associated with the condition. MATERIALS AND METHODS: Two groups of mice were used. Transgenic animals in which the murine Amyloid Precursor Protein (APP) gene has been partly replaced by the human APP including both the Swedish and London mutations and that overexpress a mutant of the human Presenilin 1 gene (PS1M146L) driven by the PDGF promoter. The transgenic mice (App(SL)/PS1(M146L)) aged 24+/-3 months were used. The second group was an age matched control group of C57 black mice. The bladders from each group were isolated, fixed in 4% paraformaldehyde and prepared for immunohistochemistry. Antibodies to the vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS) were used to identify neural structures. RESULTS: Cholinergic nerves (VAChT(+)) were observed in the inner and outer muscle bundles of App(SL)/PS1(M146L) and control mice. No major differences were noted in the distribution of these fibres. In contrast, there was a distinct difference in the innervation of the sub-urothelial layer. In App1(SL)/PS1(M146L) mice there were numerous VAChT and nNOS positive fibres in sharp contrast to the paucity of similar nerves in control animals. VAChT and nNOS did not appear to co-localise in the same nerve fibres within the lamina propria. Pairs of nerve fibres, nNOS(+) and VAChT(+), were observed to be intertwined and run in close proximity. A particularly unusual feature of the App(SL)/PS1(M146L) mouse bladder was the presence of neurones within the bladder wall. These nerve cell bodies were seen in all App(SL)/PS1(M146L) mouse bladders. The neurones could be found singly or in small ganglion like groups of cells and were located in all layers of the bladder wall (sub-urothelium, in the lamina propria adjacent to the inner muscle and within the inner muscle and outer muscle layers). No nerve cells or small ganglia were noted in any of the control bladders studied. CONCLUSIONS: There are structural differences in the bladders of App(SL)/PS1(M146L) mice compared to control animals. These differences are associated with sub-urothelial nerves which, because of their location, are likely to be sensory fibres. This may lead to a changed sensory processing from the App(SL)/PS1(M146L) bladders. The physiological role of the intra-mural neurones and ganglia is not known. It is speculated that they may be associated with peripheral motor/sensory mechanisms linked to the generation and modulation of sensation.

The localization of cyclo-oxygenase immuno-reactivity (COX I-IR) to the urothelium and to interstitial cells in the bladder wall.

Localized phasic contractions in the bladder wall (autonomous activity) have been hypothesized to be an integral part of a motor/sensory system contributing to bladder sensation. The sites responsible for generating this activity, the mechanisms involved in its propagation and modulation remain unknown. This phasic motor activity is modulated by exogenous prostaglandins. Therefore, analysis of the sites of prostaglandin production and action within the bladder wall may shed light on the mechanisms of generation and modulation of this phasic activity. In this paper we report the localization of immuno-reactivity indicative of the expression of cyclo-oxygenase enzyme type I (COX I-IR) within the bladder wall. Basically, three types of COX I-IR cell were identified: epithelial cells in the basal and intermediate layers of the urothelium, complex vimentin-positive and COX I-IR cells in the lamina propria and vimentin-negative COX I-IR cells in the lamina propria and on the surface of the inner muscle bundles. These vimentin-negative/COX I-IR cells appear to be in close apposition to a continuous network of vimentin-positive cells, which extends from the lamina propria into the inner muscle layers and subsequently into the outer muscle layers. However, the interstitial cells in this region might form a distinctly different sub-type. First, the interstitial cells in this region differ from those in the inner layer by their responsiveness to NO with a rise in cGMP. Two subtypes have been identified: cells on the surface of the muscle bundles and within the muscle bundles. Second, COX I-IR cells are not associated with the interstitial cells in the outer layers. The physiological significance for these apparent differences in the interstitial cell network is not clear. However, such differences are likely to reflect differences in the processes involved in their activation, modulation and control.

Alterations to network of NO/cGMP-responsive interstitial cells induced by outlet obstruction in guinea-pig bladder.

Interstitial cells (ICs) play a role in regulating normal bladder activity. This study explores the possibility that the sub-urothelial and muscle networks of NO/cGMP-responsive ICs are altered in animals with surgically induced outflow obstruction. In sham-operated animals, the urothelium comprised NO-stimulated cGMP-positive (cGMP(+)) umbrella cells, an intermediate layer and a basal layer that stained for nNOS. cGMP(+) sub-urothelial interstitial cells (su-ICs) were found below the urothelium. cGMP(+) cells were also associated with the outer muscle layers: on the serosal surface, on the surface of the muscle bundles and within the muscle bundles. Several differences were noted in tissues from obstructed animals: (1) the number of cGMP(+) umbrella cells and intensity of staining was reduced; (2) the intermediate layer of the urothelium consisted of multiple cell layers; (3) the su-IC layer was increased, with cells dispersed being throughout the lamina propria; (4) cGMP(+) cells were found within the inner muscle layer forming nodes between the muscle bundles; (5) the number of cells forming the muscle coat (serosa) was increased; (6) an extensive network of cGMP(+) cells penetrated the muscle bundles; (7) cGMP(+) cells surrounded the muscle bundles and nodes of ICs were apparent, these nodes being associated with nerve fibres; (8) nerves were found in the lamina propria but rarely associated with the urothelium. Thus, changes occur in the networks of ICs following bladder outflow obstruction. These changes must have functional consequences, some of which are discussed.

Predictive validity of the Golombok Rust Inventory of Sexual Satisfaction (GRISS) for the presence of sexual dysfunctions within a Dutch urological population.

The objective of this study was to investigate the predictive validity of the Dutch translation of the Golombok Rust Inventory of Sexual Satisfaction (GRISS) for the presence of clinically relevant sexual dysfunctions and patient's need of help. A total of 57 male urological outpatients (age 50.7+/-13.2 y; range 27-77 y) completed the GRISS, a 28-item self-report questionnaire assessing sexual dysfunctions and sexual satisfaction in heterosexual relationships. GRISS subscales were found to differentiate multivariately between men with and without sexual dysfunctions. The erectile dysfunction (In the original English version of the GRISS, the term 'impotence' was used instead of 'erectile dysfunction'), dissatisfaction, and infrequency subscales also differentiated univariately between these groups. The predictive validity for the presence of sexual dysfunctions and for the patients' need for professional help was investigated. Prediction models, derived by means of logistic regression analysis, were tested in a crossvalidation sample. Sensitivity and specificity for the presence of sexual dysfunctions, as well as the predictive values positive and negative were found to be satisfactory. The predictive validity of the GRISS was found equally satisfactory for the patients' need for professional help. The discriminant and predictive validity of the GRISS in men with and without sexual dysfunctions appeared satisfactory. Routine use of the GRISS appears warranted for the screening of sexual dysfunctions in new urological patients.