G. Van Koeveringe

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).

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.

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.

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.

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

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.

How should bladder sensation be measured?: ICI‐RS 2011

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.

Relaxant Effects of Estradiol through Non-Genomic Pathways in Male and Female Pig Bladder Smooth Muscle

The precise effect of low estrogen levels on urinary bladder contractility remains controversial. The present study was designed to analyze the effect of 17β-estradiol in bladder smooth muscle contractility and the involvement of specific estrogen receptor stimulation in this effect. Castrated male and female pig detrusor strips were mounted for tension recording in an organ bath, superfused with Krebs solution at 37°C and stimulated electrically and pharmacologically. In order to verify the acute effect of 17β-estradiol on muscle contractility, the strips were incubated with different concentrations of the hormone. Muscle contractions were induced by potassium chloride, acetylcholine chloride and electrical field stimulation. The involvement of the estrogen receptor in the effects of 17β-estradiol was assessed by incubation of some strips with the selective estrogen receptor antagonist ICI 182.780 before estradiol was applied. Estradiol at a dose of 30 µmol/l elicited a lower amplitude of contractions induced by EFS, Ach and KCl in female as well as in castrated male pig bladder smooth muscle strips. The effects of 17β-estradiol were stronger in contractions induced by potassium chloride than those induced by other forms of stimulation. Pre-treatment with the pure estrogen receptor antagonist had no effect on 17β-estradiol-induced inhibition of muscle contractility. These observations suggest that 17β-estradiol induces lower amplitude of contraction of female as well as castrated male pig detrusor which is not mediated by the classic estrogen receptor. Furthermore, we can conclude that estradiol has a stronger inhibitory effect on the depolarization of muscle cell membrane compared to a muscarinic receptor-induced contraction.

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 (APPSL/PS1M146L) 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.

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.

2 Three and six month results from a randomized, controlled clinical trial of an intravesical pressure-attenuation balloon system for the treatment of female stress urinary incontinence (SUI)

• The reduction in transient spikes in intravesical pressure is accomplished by insertion of a free-floating, non-occlusive intravesical balloon filled with compressible gas. Since gas is highly compressible relative to most liquids, it can act as a hydraulic “shock-absorber.” This fundamental mechanism of action has been published previously, including a prospective, randomized, single blind, multi-center study on a different patient population.1 Placement • A sheath is placed through the urethra, and cystoscopy is performed. The deflated balloon is pre-inserted inside the tip of a 19 French (Fr) delivery system and inserted into the bladder through the sheath, inflated and released.