Significant Increase In Bladder Capacity Research Articles

Transdermal tibial nerve optogenetic stimulation targeting C-fibers.

Purpose: To explore whether stimulation of C-fibers in tibial nerves can induce bladder inhibition by optogenetic transdermal illumination. Methods: Ten rats were injected with AAV2/6-hSyn-ChR2(H134R)-EYFP into the tibial nerves. Transurethral cystometry was performed 4 weeks after the virus injection. Illumination (473-nm blue light at 100mW) was performed with the fiber positioned above the right hind paw near the ankle. The light transmission efficiency was examined with a laser power meter. The effects on cystometry were compared before and after illumination with the bladder infused with normal saline and acetic acid, respectively. Result: Upon transdermal delivery of 473-nm light at a peak power of 100mW, the irradiance value of 0.653mW/mm2 at the target region was detected, which is sufficient to activate opsins. The photothermal effect of 473-nm light is unremarkable. Acute inhibitory responses were not observed during stimulation regarding any of the bladder parameters; whereas, after laser illumination for 30min, a statistically significant increase in bladder capacity with the bladder infused with normal saline (from 0.53 ± 0.04mL to 0.72 ± 0.05mL, p < 0.001) and acetic acid (from 0.25 ± 0.02mL to 0.37 ± 0.04mL, p < 0.001) was detected. A similar inhibitory response was observed with pulsed illumination at both 10Hz and 50Hz. However, illumination did not significantly influence base pressure, threshold pressure, or peak pressure. Conclusion: In this preliminary study, it can be inferred that the prolonged bladder inhibition is mediated by the stimulation of C-fibers in the tibial nerves, with no frequency-dependent characteristics. Although the 473-nm blue light has limited penetration efficacy, it is sufficient to modulate bladder functions through transdermal illumination on the superficial peripheral nervous system.

PD23-01 EFFECT OF OPIOID RECEPTOR ANTAGONIST ON BLADDER UNDERACTIVITY INDUCED BY PROLONGED PUDENDAL AFFERENT STIMULATION

You have accessJournal of UrologyCME1 Apr 2023PD23-01 EFFECT OF OPIOID RECEPTOR ANTAGONIST ON BLADDER UNDERACTIVITY INDUCED BY PROLONGED PUDENDAL AFFERENT STIMULATION Michael Pintauro, Jianan Jian, Jicheng Wang, Bing Shen, Zhijun Shen, Khari Goosby, Joseph Scolieri, Avanish Madhavaram, Jonathan Beckel, William De Groat, Christopher Chermansky, and Changfeng Tai Michael PintauroMichael Pintauro More articles by this author , Jianan JianJianan Jian More articles by this author , Jicheng WangJicheng Wang More articles by this author , Bing ShenBing Shen More articles by this author , Zhijun ShenZhijun Shen More articles by this author , Khari GoosbyKhari Goosby More articles by this author , Joseph ScolieriJoseph Scolieri More articles by this author , Avanish MadhavaramAvanish Madhavaram More articles by this author , Jonathan BeckelJonathan Beckel More articles by this author , William De GroatWilliam De Groat More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , and Changfeng TaiChangfeng Tai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Fowler Syndrome, or non-obstructive urinary retention, is seen in young female patients. Although the cause is unknown, it is theorized that aberrant sensory nerves from the urethral sphincter cause inhibition of the central nervous system, thereby leading to urinary retention. Prior studies have suggested that the opioid receptor may be implicated in bladder overactivity and underactivity. We aimed to evaluate opioid receptor inhibition on bladder function in a feline model of Fowler’s Syndrome. METHODS: A total of 10 cats were anesthetized, ureters externalized via laparotomy, and urethral catheter placed. A tripolar cuff electrode was placed on the pudendal nerve. Multiple cystometrograms (CMGs) were performed to determine baseline bladder function (Control). Multiple pudendal nerve stimulations (PNS) were performed at 30-minute cycles (5 Hz, 0.2 ms) were applied at 4-6 times the intensity required to elicit anal contraction for 2-5 hours. The result was a stable, underactive bladder state (Post-PNS 1). Next, naloxone (1mg/kg IV) was administered, and CMGs obtained (Post-NX). A single 30-minute PNS was then performed to evaluate the combined effect of naloxone and PNS (Post-PNS 2). Lastly, a CMG was performed to examine any recovery (Post-Control). Primary outcomes were bladder capacity and contraction amplitude (contractility). RESULTS: Application of PNS produced a significant increase in bladder capacity and decrease in bladder amplitude, indicative of a state of bladder underactivity (Figure 1, * denotes significance p<0.05). Administration of naloxone significantly reduced the bladder capacity and increased contraction amplitude. Re-application of PNS led fully overcame the naloxone effect on capacity; however, the amplitude is a combined effect. This effect of re-stimulation lasted only for a short period (15-20 minutes) and Post-Control demonstrate a reduction in capacity indicating effects of the still present naloxone overcoming the PNS. CONCLUSIONS: Pharmacologic opioid receptor antagonism increased bladder contractility and reduced bladder capacity to baseline in our feline model of non-obstructive urinary retention. This is a new target for possible pharmacotherapy in the treatment of patients with Fowler's Syndrome. Source of Funding: 5R01DK121698-02 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e670 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Pintauro More articles by this author Jianan Jian More articles by this author Jicheng Wang More articles by this author Bing Shen More articles by this author Zhijun Shen More articles by this author Khari Goosby More articles by this author Joseph Scolieri More articles by this author Avanish Madhavaram More articles by this author Jonathan Beckel More articles by this author William De Groat More articles by this author Christopher Chermansky More articles by this author Changfeng Tai More articles by this author Expand All Advertisement PDF downloadLoading ...

Feasibility and Efficacy of Transdermal Hypogastric Nerve Stimulation in Treatment of Overactive Bladder in Multiple Sclerosis: A Prospective Randomized Controlled Trial

Objective: To determine the feasibility and efficacy of transdermal hypogastric nerve stimulation by interferential current stimulation (IFCs) in the treatment of OABs in relapsing-remitting multiple sclerosis (RRMS). Material and Methods: Forty male RRMS patients with moderate overactive bladder symptoms were randomly assigned into two equal groups; the control group (G1) was treated with selected therapeutic exercises for strengthening the pelvic floor muscles, and the intervention group (G2) received the same regimen plus hypogastric nerve stimulation at T10-L2 by interferential current (IFC). In both groups, the duration of each session ranged from 40-45 minutes, three days weekly for a month. Pre and post treatment evaluation was done by Overactive bladder symptom score (OABSS) included (daytime frequency, nocturia, urgency, and urgency incontinence) and Urodynamics tests included (bladder capacity, maximum flow rate, bladder compliance, detrusor instability) and post voiding residual urine measurement by abdominal ultrasound. The effect of treatment on bladder capacity, maximum flow rate, post void residual, bladder compliance and OVBSS was investigated using a mixed MANOVA. The Mann Whitney test was used to evaluate the detrusor instability between groups, and the Wilcoxon signed ranks test was used to compare pre and post treatment in each group. The level of significance was set at p &lt; 0.05 for all statistical tests. Results: Showed that a significant increase in bladder capacity, bladder compliance, percentage of detrusor stability and maximal flow rate and a significant decrease in post void residual post treatment in comparison with pretreatment (p &lt; 0.05) in both groups. There was a significant decrease in the daytime and nighttime frequency and urgency post treatment compared with that pretreatment in both groups (p &gt; 0.001) while a significant decrease of urgency incontinence in the study group only post treatment compared with that pretreatment (p &gt; 0.001). Post treatment, there was a significant difference of the intervention group (G2) compared with that of the control group (G1) for all tested variables (P&lt; 0.05) except for the daytime frequency and percentage of detrusor stability (p &gt; 0.05). Conclusions: Transdermal hypogastric nerve stimulation using IFC could be considered a feasible treatment option for neurogenic OABs in multiple sclerosis patients.

Sacral neuromodulation of bladder underactivity induced by prolonged pudendal afferent firing in cats.

This study examined the effect of sacral neuromodulation on persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PudNS). In 10 α-chloralose-anesthetized cats, repetitive application of 30-min PudNS induced bladder underactivity evident as an increase in bladder capacity during a cystometrogram (CMG). S1 or S2 dorsal root stimulation (15 or 30 Hz) at 1 or 1.5 times threshold intensity (T) for inducing reflex hindlimb movement (S1) or anal sphincter twitch (S2) was applied during a CMG to determine if the stimulation can reverse the bladder underactivity. Persistent (>3 h) bladder underactivity consisting of a significant increase in bladder capacity to 163.1 ± 11.3% of control was induced after repetitive (1-10 times) application of 30-min PudNS. S2 but not S1 dorsal root stimulation at 15 Hz and 1 T intensity reversed the PudNS-induced bladder underactivity by significantly reducing the large bladder capacity to 124.3 ± 12.9% of control. Other stimulation parameters were not effective. After the induction of persistent underactivity, recordings of reflex bladder activity under isovolumetric conditions revealed that S2 dorsal root stimulation consistently induced the largest bladder contraction at 15 Hz and 1 T when compared with other frequencies (5-40 Hz) or intensities (0.25-1.5 T). This study provides basic science evidence consistent with the hypothesis that abnormal pudendal afferent activity contributes to the bladder underactivity in Fowler's syndrome and that sacral neuromodulation treats this disorder by reversing the bladder inhibition induced by pudendal nerve afferent activity.

Overactive Bladder as a Key Driver of Nocturia: The Argument Against

Studies have shown that therapies for overactive bladder reduce urgency symptoms. However, these studies fail to demonstrate clinically significant increases in bladder capacity or changes in mean voided volumes at night.

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8 ± 10.9% of control and a significant reduction in bladder contraction amplitude to 56.0 ± 5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4 ± 10.7% and 132.4 ± 14.2% of control, respectively, and increased contraction amplitude to 85.3 ± 6.2% and 75.8 ± 4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Efficacy and safety of Mirabegron as adjuvant treatment in children with refractory neurogenic bladder dysfunction

When patients with neurogenic bladder become refractory, there are different alternatives, such as the use of β3-adreceptor agonists. The aim of the present study is to evaluate efficacy and safety of Mirabegron as adjuvant treatment. 37 patients under 18 years of age who underwent Mirabegron were retrospectively studied. The inclusion criteria were: cases with neurogenic bladder who were under clean intermittent catheterization (CIC) programs and refractory to oral oxybutynin (Group A) and/or onabotulinumtoxinA (Group B). Once refractory neurogenic bladder was confirmed by clinical and/or urodynamic studies, Mirabegron 25mg/day was indicated and evaluation was performed in the third month without stopping therapy. Systolic/diastolic blood pressure and transaminases were monitored. Paired t test and Pearson's chi - squared test were used. Maximum cystometric capacity increased significantly by 125mL, from 322 to 446ml (p<0.0001). End-filling detrusor pressure decreased significantly by 12cm H2O, from 44 to 31cm H2O (p<0.0001). The variation in both parameters was significant in Groups A and B. The presence of detrusor overactivity increased globally from 21 to 32% after starting Mirabegron, but the intensity of contractions was reduced in 20cm H2O. Of the 18 patients who were incontinent before, 13 cases (72%) remained dry after initiating therapy with Mirabegron. None of the patients stated having suffered any adverse effects. Blood pressure and transaminases showed no significant difference. None of the patients discontinued treatment due to intolerance to Mirabegron (Summary Table). In our study the treatment with Mirabegron improved significantly the clinical and urodynamic parameters. A significant increase in bladder capacity and a significant decrease in end-filling detrusor pressure were observed in both groups. The intensity of overactivity was attenuated. According to the records of the voiding diary, over 70% of the incontinent patients became dry after the administration of Mirabegron. We did not observe any adverse effects. The most important limitations of the present study are its retrospective design, the small size of the sample population and of each group, and the use of only one dose of Mirabegron. Mirabegron as adjuvant treatment in children with refractory neurogenic bladder increased bladder capacity, reduced intravesical pressure and helped achieve continence in more than two thirds of the sample population. Mirabegron was safe and well tolerated by children.

Long-term follow-up of neurogenic bladder patients after bladder augmentation with small intestinal submucosa.

To evaluate the long-term effect of using small intestinal submucosa (SIS) for bladder augmentation in patients with neurogenic bladder. A total of 15 patients (age range 14-65years; mean age 29.6years) were enrolled in our study. The patients had poor bladder capacity and compliance caused by a neurogenic disorder requiring bladder augmentation. A small intestinal submucosa (SIS) cystoplasty was performed alone or in combination with ureter reimplantation. We prospectively followed the cohort to assess the urodynamics parameters, morphologic changes and patient satisfaction and evaluate the clinical benefit of the SIS procedure in long term. The surgical indications and complications were analyzed. The duration of follow-up ranged from 4.5 to 8.3years (mean 6.3years). Nine patients had expected long-term benefit, leading to an overall success rate of 60%. Two patients experienced immediate failure, and four patients slowed decrease in bladder capacity over time. Compared with the baseline data, there were significant increases in bladder capacity (163.5 ± 80.90-275.6 ± 159.5ml, p < 0.05) and a significant decrease in maximum detrusor pressure (45.07 ± 29.03-17.60 ± 10.34 cmH2O, p < 0.05). Histologic examinations showed a complete conversion of SIS, leaving the urothelial lining and bladder wall containing muscular, vascular, and relatively thick connective tissue. Major complications included vesicoureteral reflux in five patients, bladder stone formation in one patient, and bladder perforation in one patient. Bladder augmentation with an SIS graft offers a partial long-term success rate in neurogenic bladder patients. This procedure cannot be recommended as a substitute for enterocystoplasty, especially in patients with severe upper urinary tract deterioration and/or bladder fibrosis.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

ObjectiveLocomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury).Study designProspective cohort study; pilot trial with small sample size.MethodsEight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart.ResultsFilling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants.ConclusionsThese results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions.Trial registrationClinicalTrials.gov NCT03036527

Conditional neuromodulation of neurogenic detrusor overactivity using transrectal stimulation in patients with spinal cord injury: A proof of principle study.

AimsA proof of principle study of a novel wearable device to control neurogenic detrusor over‐activity in eight male spinal cord injured subjects using conditional neuromodulation.MethodsTransrectal stimulation was delivered through the device in response to simultaneously recorded external anal sphincter (EAS) contraction as a marker for neurogenic detrusor overactivity (NDO). The effect of conditional neuromodulation on bladder capacity and maximum detrusor pressure was investigated in addition to reliability of dyssynergic sphincter contraction as a marker for NDO.ResultsConditional neuromodulation through the novel device showed a statistically significant increase in bladder capacity and reduction in maximum detrusor pressure in six male subjects with spinal cord injury (SCI). EAS activity was a reliable surrogate for detection of NDO.ConclusionsIt has been shown for the first time that conditional neuromodulation can be delivered and triggered via a single biocompatible device placed in the anal canal. The pudendal nerves lying in Alcock's canal were stimulated through the wall of the anal canal, and the dyssynergic activity of the EAS was used to detect NDO and trigger neuromodulation giving significant increases in bladder capacity and reduction in detrusor pressure in six male subjects with SCI.

Long-Term Sacral Magnetic Stimulation for Refractory Stress Urinary Incontinence

ObjectiveTo evaluate the effects of sacral magnetic stimulation (SMS) on functional and urodynamic improvement in patients with refractory stress urinary incontinence (SUI). DesignA sham-controlled, double-blind, parallel study design with a 4.5-month follow-up. SettingA tertiary hospital. ParticipantsWomen (age, 45–75y) with SUI refractory to first-line management (N=34) were allocated to either an experimental (n=20) group or a sham (n=14) group. InterventionsThe SMS protocol consisted of 5-Hz, 20-minute treatments administered over the bilateral third sacral roots, with the intensity set at approximately 70% of the maximal output, for 12 consecutive weekdays. Main Outcome MeasuresUrodynamic assessments and 2 life stress questionnaires, namely, the Urge-Urinary Distress Inventory (U-UDI) and the Overactive Bladder Questionnaire (OAB-q), were administered pre- and post-SMS intervention. We administered the U-UDI (primary outcome measure) and the OAB-q at 3-week intervals during the follow-up period until 18 weeks after the final intervention. ResultsThe experimental group exhibited significant improvements in both U-UDI and OAB-q scores postintervention (P=.011–.014) and at follow-up visits (P<.001–.007) compared with the sham group. In addition, significant increases in bladder capacity, urethral functional length, and the pressure transmission ratio (P=.009–.033) were noted postintervention. Multivariate regression analysis revealed that patients with more severe symptoms benefited more from SMS. A poorer baseline U-UDI score and a shorter urethral functional length were associated with a greater response to SMS. ConclusionsOur observations of a greater response to SMS in patients with more severe SUI than in those with mild symptoms, as well as the long-term benefits of the treatment, confirm the efficacy of SMS in treating SUI.

Neuromodulation on Bladder Capacity in Conscious Sheep1

Neuromodulation on Bladder Capacity in Conscious Sheep1

Outcomes of electrical stimulation of the neurogenic bladder: Results of a two-year follow-up study

The complications of neurogenic dysfunction of the urinary bladder still constitute an important cause of death among spinal cord injury patients. The aim of this study was to assess transcutaneous electrical stimulation of the urinary bladder as a treatment for micturition disorders in patients after spinal cord injury (SCI) over 2 years of follow-up. The study involved 28 patients (22 men and 6 women) with neurogenic bladder dysfunction following a spinal cord injury. The patients were 16 to 68 years old and 2 to 26 months since their spinal cord injury. The therapeutic programme involved 30 sessions of electrical stimulation of the urinary bladder, five sessions per week. The outcomes of electrical stimulation were assessed by comparing the results of urodynamic examinations performed before treatment, immediately on completion of the treatment and at 24 months post-treatment. Transcutaneous electrical stimulation of the urinary bladder produced a significant increase in bladder capacity (p = 0.001), which was higher by a mean of 117.7 ml immediately on completion of the treatment and a mean of 101.6 ml (p = 0.018) two years after the treatment. The amount of post-void residual urine in the bladder decreased by a mean of 81.9 ml (p = 0.007) immediately after completion of the treatment and a mean of 76.9 ml (p = 0.011) two years after the treatment. Opening pressure was lower by a mean of 3.1 cm H₂O (p > 0.05) immediately on completion of the electrical stimulation treatment. Intravesical pressure at maximum flow decreased in 19 patients (68%) by a mean of 11.6 cm H₂O (p > 0.05). At the late follow-up assessment, opening pressure was lower in 17 patients (68%) by a mean of 6.7 cm H₂O. Two patients demonstrated the micturition phase, which had been absent at baseline and immediately after completion of the treatment. Opening pressure in the entire group was lower compared to baseline by 2.9 cm H₂O (p > 0.05). Also in the late follow-up assessment, intravesical pressure at maximum flow was reduced in 21 patients (79%) by a mean of 9.6 cm H₂O (p > 0.05). The maximum voiding velocity increased by a mean of 3.8 ml/s (p = 0.008) immediately after treatment completion and by a mean of 3.6 ml/s (p < 0.001) at two years post-treatment. Transcutaneous electrical stimulation of the neurogenic bladder in patients following spinal cord injury improves lower urinary tract function. Improved urinary tract function is seen two years following completion of the electrical stimulation treatment.

Effects of Vitamin D Analog on Bladder Function and Sensory Signaling in Animal Models of Cystitis

To measure the effects of nonhypercalcemic vitamin D receptor agonist elocalcitol on bladder function in rats with cyclophosphamide-induced cystitis and on bladder function and sensory nerve activity in a mouse with acetic acid-evoked bladder irritation. Female Wistar rats and male Balb/C mice were gavaged once daily with elocalcitol diluted in miglyol 812 (treatment group) or miglyol alone (control group). On experimental day 12, polyethylene tubing was implanted into the urinary bladder in all the animals. In the mice, a bipolar electrode was positioned under a single postganglionic bladder nerve. At 48 hours after surgery, bladder function was measured in awake, freely moving rats during bladder filling with 0.9% NaCl and both bladder function and sensory nerve activity was measured in awake, restrained mice during continuous intravesical infusion of 0.9% NaCl followed by 0.25% acetic acid. In rats, the treatment group showed a significant increase in bladder capacity and decrease in number of nonvoiding bladder contractions. In mice, the filling pressure during saline infusion was similar in both groups; however, during acetic acid infusion, the average filling pressure was significantly increased (47%) in the control group but not in the elocalcitol treatment group. The firing rate at filling pressure for the treatment group was 3.6-fold and 2.7-fold lower than that in the control group during the saline and acetic acid infusion, respectively. Oral treatment with elocalcitol suppressed signs of detrusor overactivity in both animal models and exerted strong suppressive effect on urinary bladder sensory signaling during filling in mice.

Augmentation cystoplasty: diagnosis, treatment and outcome

BACKGROUND: Augmentation cystoplasty is an accepted treatment modality for medically refractory neurogenic bladder dysfunction and malformed bladder by providing a highcapacity reservoir with low bladder pressure. A continent urinary diversion is often performed concomitantly for easier clean intermittent catheterization. METHODS: The patient records of 26 (m:w = 13:13; mean age 13 a) children who underwent augmentation cystoplasty between February 1995 and February 2011 were reviewed retrospectively. In follow-up, standardized interviews were performed and all patients underwent ultrasound, videourodynamic or voiding cystography and cystomanometry. Additionally, blood analyses (e.g. creatinine level, electrolytes and vitamin B12 level) were carried out. All complications were evaluated. RESULTS: Augmentation cystoplasty and continent urinary diversion were performed in 26 and 16 patients. Postoperative videourodynamic revealed a significant increase in bladder capacity (mean 569.7 ml; p-value < 0.001) and bladder compliance (mean 51 ml/cm H2O; p-value < 0.001). Postoperatively 22 patients were socially continent. The most common complications were insufficiency and stricture of continent urinary diversion (56%;) and bladder calculi (23%;). One patient needed re-do of augmentation, due to a thrombosis of the ileocystoplasty, another developed intestinal obstruction and another showed insufficiency of the anastomosis, therefore a revision was performed. No malignancy was found. Renal function stayed stable in 25 children and improvement was found in 1 patient. CONCLUSIONS: Augmentation cystoplasty can increase the bladder volume and the bladder compliance. This procedure allows the majority of patients to achieve continence and to stabilize renal function. Careful follow-up is necessary for early recognition of complications e.g. malignancies and stones.

Co‐administration of an α1‐blocker improves the efficacy and safety of antimuscarinic agents in rats with detrusor overactivity

To investigate the efficacy and safety of a combination treatment with α(1)-blockers and antimuscarinics for detrusor overactivity in rats. Rats with detrusor overactivity caused by a cerebral infarction were divided into four groups that received an i.v. administration of tamsulosin (0.1-1000 µg/kg); solifenacin (0.01-0.3 mg/kg); combined low doses of tamsulosin (0.008, 0.1 µg/kg) and solifenacin (0.01 mg/kg); or solifenacin (0.1, 0.3, 1.0 mg/kg) at 1-h intervals during the continuous administration of tamsulosin (0.01 µg/kg/h). Both tamsulosin alone and solifenacin alone significantly increased bladder capacity in cerebral infarcted rats, but these effects were reduced in rats pretreated with resiniferatoxin. The combined low dose of tamsulosin and solifenacin resulted in a significant increase in bladder capacity compared to mono-administration of 0.01 mg/kg solifenacin (68.8 vs 19.8% of control value, respectively). In the group receiving solifenacin at 1-h intervals, solifenacin dose-dependently decreased bladder contraction duration and a significant reduction in bladder contraction pressure (by 35.0% of control value) was found at the highest dose (1.0 mg/kg). However, no reduction in bladder contraction duration was found even at the highest dose of solifenacin when co-administered with tamsulosin. α(1)-Blockers and antimuscarinic agents have an additive ameliorative effect on detrusor overactivity when co-administered at low doses. α(1)-Blockers prevent the reduction in bladder contraction duration induced by a high-dose administration of antimuscarinic agents.

Urethral Sensations are Related to the Development of Detrusor Overactivity.

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation

Currently, gastrointestinal segments are considered the gold standard for bladder reconstructive procedures. However, significant complications including chronic urinary tract infection, metabolic abnormalities, urinary stone formation, bowel dysfunction, and secondary malignancies are associated with this approach. Biomaterials derived from silk fibroin may represent a superior alternative due their robust mechanical properties, biodegradable features, and processing plasticity. In the present study, we evaluated the efficacy of a gel spun silk-based matrix for bladder augmentation in a murine model. Over the course of 70 d implantation period, H&E and Masson’s trichrome (MTS) analysis revealed that silk matrices were capable of supporting both urothelial and smooth muscle regeneration at the defect site. Prominent uroplakin and contractile protein expression (α-actin, calponin, and SM22α) was evident by immunohistochemical analysis demonstrating maturation of the reconstituted bladder wall compartments. Gel spun silk matrices also elicited a minimal acute inflammatory reaction following 70 d of bladder integration, in contrast to parallel assessments of small intestinal submucosa (SIS) and poly-glycolic acid (PGA) matrices which routinely promoted evidence of fibrosis and chronic inflammatory responses. Voided stain on paper analysis revealed that silk augmented animals displayed similar voiding patterns in comparison to non surgical controls by 42 d of implantation. In addition, cystometric evaluations of augmented bladders at 70 d post-op demonstrated that silk scaffolds supported significant increases in bladder capacity and voided volume while maintaining similar degrees of compliance relative to the control group. These results provide evidence for the utility of gel spun silk-based matrices for functional bladder tissue engineering applications.

Type 4 phosphodiesterase inhibitor suppresses experimental bladder inflammation

To evaluate the effects of orally administered YM976, a specific inhibitor of type 4 phosphodiesterase (PDE4), on bladder activity in a rat model with hydrochloric acid (HCl)-induced cystitis (IC), hypothesizing that a PDE4 inhibitor might suppress bladder overactivity and bladder pain responses in bladder-hypersensitive disorders such as IC. Wistar rats with HCl-induced IC were treated with YM976 or vehicle and their voiding observed and assessed by cystometry. The severity of bladder inflammation (BI) was quantified using the BI index (BII), which comprises three factors (oedema, leukocyte infiltration and haemorrhage). Nociceptive neural activity was also examined using an immunohistochemical study of spinal c-fos expression. YM976 significantly reduced the number of voids, and the volume per void was significantly higher than in control (vehicle) group. Cystometry showed a significant increase in bladder capacity, voided volume and voiding efficiency, and a decrease in the amplitude of voiding pressure in rats treated with YM976. All BII scores were significantly lower in the YM976 than in the control group. c-fos expression in the spine was less in the YM976 than in the control group. Oral administration of YM976 significantly improved the voiding behaviour and histological damage in rats with IC induced by HCl. These results indicate that PDE4 inhibitor might be effective in relieving bladder symptoms with IC.

Are urodynamic studies really needed during bladder augmentation follow-up?

Objective We assessed clinical and urodynamic outcomes, over a minimum 10-year follow-up period, of neuropathic bladder patients treated with a bladder augmentation (BA) to determine if periodic urodynamic studies are needed. Material and methods Thirty-two patients with poorly compliant bladders underwent BA at a mean age of 11 years (2.5–18). Mean follow-up was 12 years (10–14.5) and mean patient age at the end of the study was 22 years (12.2–33). During follow-up all patients were controlled at regular intervals with urinary tract imaging, serum electrolyte and creatinine levels, cystoscopy and urodynamic studies. Preoperative, 1-year post-BA and latest urodynamic studies results were compared. Results Urodynamic studies at 1-year post-BA showed a significant increase in bladder capacity and a decrease in end-filling detrusor pressure compared with preoperative values (396 vs 106 ml; 10 vs 50 cm H 2O, P < 0.0001). The increase in bladder capacity was more significant at the end of the study than after 1 year (507.8 vs 396 ml, P < 0.002). Thirteen patients had phasic contractions after 1 year and 11 at the end (not significant, NS), and these contractions were more frequent with colon than with ileum (NS). At the end of follow-up, phasic contraction pressure had decreased while trigger volume had increased (35 vs 28 cm H 2O; 247 vs 353 ml, NS). All patients are dry and have normal renal function, except one who had mild renal insufficiency before BA. Conclusion BA improves bladder capacity and pressure, and these changes are maintained over time (although phasic contractions do not disappear). Repeated urodynamic studies are only necessary when upper urinary tract dilatation or incontinence does not improve.