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OBJECTIVE To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P

Objectives To elucidate the mechanism of action of the α1 -blocker, naftopidil, in partial bladder outlet obstruction animals, by studying non-voiding contractions, and the levels of mediators were measured with resiniferatoxin treatment. Methods A total of 35 female Wistar rats were randomly divided into a sham or bladder outlet obstruction group, and rats in each group were given vehicle or resiniferatoxin. Incomplete urethral ligation was applied to the bladder outlet obstruction group. After cystometry, the intravesical level of prostaglandin E2 and adenosine 5'-triphosphate was measured in the instilled perfusate collected. Naftopidil was given at the time of cystometry. Results In bladder outlet obstruction rats, non-voiding contractions, bladder capacity, and the intravesical levels of prostaglandin E2 and adenosine 5'-triphosphate were markedly increased compared with sham rats. Naftopidil decreased non-voiding contractions, enlarged the bladder capacity, and decreased the intravesical levels of prostaglandin E2 and adenosine 5'-triphosphate. Resiniferatoxin enhanced non-voiding contractions. The effects of naftopidil on non-voiding contractions and the intravesical level of prostaglandin E2 , but not adenosine 5'-triphosphate, were tolerant to resiniferatoxin. Conclusions In bladder outlet obstruction rats, one cause of generation of non-voiding contractions might be bladder wall distension, but not transient receptor potential cation channel V1. The increase in intravesical prostaglandin E2 might also be associated with the generation of non-voiding contractions. Naftopidil inhibits the increase in non-voiding contractions and decreases the intravesical level of prostaglandin E2 , which are independent of transient receptor potential cation channel V1.

Stress-related peptide corticotropin-releasing factor (CRF) and CRF-related peptides are distributed in the peripheral viscera such as the bladder. We investigated the contribution of psychological stress (PS) and CRF on bladder function. Male rats received sham stress (SS) or PS using a communication box method for 120 min every day for 7 days. One group of rats received the intraperitoneal CRF-R1 antagonist antalarmin for 7 days during stress exposure. Mean voided volume per micturition was significantly lower in PS rats compared to SS rats, which was antagonized by antalarmin treatment. Increases in plasma and bladder CRF, and mRNA expressions of bladder CRF, CRF-R1, and M2/3 muscarinic receptors, were found in PS rats. CRF did not influence bladder contraction in itself; however, stress increased the response of muscarinic contraction of bladder strips. These changes were antagonized by antalarmin treatment. In conclusion, PS reinforces M3 receptor-mediated contractions via CRF-R1, resulting in bladder storage dysfunction.

INTRODUCTION AND OBJECTIVES:Recent reports indicate that there may be a physiological link between hypogonadism and metabolic syndrome (MetS) (J Androl 2009, 30: 370). In fact, hyperinsulinemia and...

INTRODUCTION AND OBJECTIVES:Surgical therapy is an important therapeutic strategy for benign prostatic hyperplasia (BPH). However, the degree of improvement in postoperative clinical parameters can...

To elucidate the mechanism of action of the αA total of 35 female Wistar rats were randomly divided into a sham or bladder outlet obstruction group, and rats in each group were given vehicle or resiniferatoxin. Incomplete urethral ligation was applied to the bladder outlet obstruction group. After cystometry, the intravesical level of prostaglandin EIn bladder outlet obstruction rats, non-voiding contractions, bladder capacity, and the intravesical levels of prostaglandin EIn bladder outlet obstruction rats, one cause of generation of non-voiding contractions might be bladder wall distension, but not transient receptor potential cation channel V1. The increase in intravesical prostaglandin E

This study was aimed at determining the effect of duloxetine (a serotonin-norepinephrine reuptake inhibitor) on pudendal inhibition of bladder overactivity. Cystometrograms were performed on 15 cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, pudendal nerve stimulation (PNS) at 5 Hz was applied to the right pudendal nerve at two and four times the threshold (T) intensity for inducing anal twitch. Duloxetine (0.03–3 mg/kg) was administered intravenously to determine the effect on PNS inhibition. AA irritation significantly (P < 0.01) reduced bladder capacity to 27.9 ± 4.6% of saline control capacity. PNS alone at both 2T and 4T significantly (P < 0.01) inhibited bladder overactivity and increased bladder capacity to 83.6 ± 7.6% and 87.5 ± 7.7% of saline control, respectively. Duloxetine at low doses (0.03–0.3 mg/kg) caused a significant reduction in PNS inhibition without changing bladder capacity. However, at high doses (1–3 mg/kg) duloxetine significantly increased bladder capacity but still failed to enhance PNS inhibition. WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide; a 5-HT1A receptor antagonist, 0.5–1 mg/kg i.v.) reversed the suppressive effect of duloxetine on PNS inhibition and significantly (P < 0.05) increased the inhibitory effect of duloxetine on bladder overactivity but did not enhance the effect of PNS. These results indicate that activation of 5-HT1A autoreceptors on the serotonergic neurons in the raphe nucleus may suppress duloxetine and PNS inhibition, suggesting that the coadministration of a 5-HT1A antagonist drug might be useful in enhancing the efficacy of duloxetine alone and/or the additive effect of PNS-duloxetine combination for the treatment of overactive bladder symptoms.

The objective of the present study was to investigate the matrix protein of a rare urinary stone that contained calcium carbonate. A urinary stone was extracted from a 34-year-old male patient with metabolic alkalosis. After X-ray diffractometry and infrared analysis of the stone, proteomic analysis was carried out. The resulting mass spectra were evaluated with protein search software, and matrix proteins were identified. X-ray diffraction and infrared analysis confirmed that the stone contained calcium carbonate and calcium oxalate dihydrate. Of the identified 53 proteins, 24 have not been previously reported from calcium oxalate- or calcium phosphate-containing stones. The protease inhibitors and several proteins related to cell adhesion or the cytoskeleton were identified for the first time. We analyzed in detail a rare urinary stone composed of calcium carbonate and calcium oxalate dihydrate. Considering the formation of a calcium carbonate stone, the new identified proteins should play an important role on the urolithiasis process in alkaline condition.

Aims To determine whether transcutaneous foot stimulation combined with a lower dose tolterodine would inhibit bladder overactivity more effectively than either treatment alone. Methods Cystometrograms were performed on α-chloralose anesthetized cats (N = 6) by infusing 0.25% acetic acid (AA) to induce bladder overactivity. Foot stimulation (5 Hz) was applied at 2 and 4 times the threshold (T) intensity in volts (i.e., 2T or 4T) for inducing toe movement to inhibit bladder overactivity. Cumulative doses of tolterodine (0.003–0.3 mg/kg, i.v.) were also administered to determine the effect of combination treatment. Results AA irritation of the bladder significantly (P

We determined the role of opioid and metabotropic glutamate 5 receptors in the pudendal inhibition of bladder overactivity.Cystometrograms were performed in 11 cats under α-chloralose anesthesia by slowly infusing the bladder with saline or 0.25% acetic acid. Pudendal nerve stimulation at intensities of multiple times the threshold to induce observable anal twitching was applied during cystometrogram to inhibit the bladder overactivity induced by acetic acid irritation. Naloxone (0.1, 0.3 and 1 mg/kg intravenously) was administered to block opioid receptors, followed by MTEP (3 and 10 mg/kg intravenously) to block metabotropic glutamate 5 receptors. After each drug dose, pudendal inhibition of bladder overactivity was examined during cystometrogram.Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased mean ± SE bladder capacity to 23.6% ± 2.7% of saline control capacity. Pudendal nerve stimulation at 1 to 1.5 and 4 × threshold suppressed bladder overactivity and significantly increased mean capacity to 57.5% ± 8.1% (p = 0.0005) and 106% ± 15% (p = 0.0002), respectively, of saline control capacity. Naloxone had no effect on pudendal inhibition but MTEP eliminated the inhibition induced by low intensity stimulation and significantly decreased the inhibition induced by high intensity stimulation (p0.05). Neither naloxone nor MTEP altered baseline bladder overactivity.Opioid receptors are not involved in pudendal inhibition of bladder overactivity but metabotropic glutamate 5 receptors are partially involved. Understanding neurotransmitter mechanisms could improve the efficacy of neuromodulation therapy for overactive bladder and identify molecular targets for developing new drugs for overactive bladder.

We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity.Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition.Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment.This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects.

INTRODUCTION AND OBJECTIVES: The impact of delivery mode and number of deliveries on urinary incontinence (UI) has been debated, and vaginal delivery has been suggested as a risk factor for female UI. Other potential factors include age, body mass index (BMI), parity, smoking, diabetes mellitus, and hysterectomy. We investigated whether delivery mode and number of deliveries is associated with UI among Japanese women. METHODS: We investigated 514 women recruited from outpatient departments (except the departments of pediatrics, psychiatry and ophthalmology) at our university hospital, regardless of the reason for visiting, during a 2-week period (from August 6 to August 17, 2007). All participants were asked to answer a standardized self-reported questionnaire. Using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), overactive bladder symptom score (OABSS), and an original questionnaire, we evaluated urinary symptoms and delivery mode history. We analyzed the impact of mode and number of deliveries on UI. The chi-square test and logistic regression modeling were used for statistical analyses. Values of P

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.

Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume.Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration.Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed.Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Aims To clarify the effects of zolpidem, a γ-aminobutyric acid (GABA)A receptor agonist, on bladder function, and urine production, we investigated the effects of zolpidem administration on bladder overactivity induced by cerebral infarction (CI) and on urine excretion increased by water overloading in Wistar rats. Methods CI was induced by left middle cerebral artery occlusion. The effects on bladder function of zolpidem alone or in combination with the GABAA receptor antagonist bicuculline, were then examined in the CI rats using cystometry. The antidiuretic effect of zolpidem was investigated in water-loaded and Brattleboro rats (genetically vasopressin-deficient). Blood samples were collected from water-loaded rats to determine the aldosterone level 1 and 6 hr after zolpidem administration. Results Zolpidem increased bladder capacity dose-dependently, but had no significant effect on bladder contraction pressure in CI rats. Bicuculline dose-dependently inhibited zolpidem-induced increases in bladder capacity without affecting bladder contraction pressure. Zolpidem dose-dependently decreased the volume of urine excreted in water-loaded and Brattleboro rats. Compared with the control group, zolpidem significantly increased the aldosterone concentration in the plasma of water-loaded rats 1 hr after administration. Conclusions Zolpidem increased bladder capacity via a GABAergic mechanism in CI rats, and suppressed urine excretion via a pathway that was not through activation of vasopressin V2 receptors in water-loaded and Brattleboro rats. These results suggest that zolpidem may improve nocturia via an increase in bladder capacity and a decrease in urine excretion. Neurourol. Urodynam. 29:587–591, 2010. © 2009 Wiley-Liss, Inc.

INTRODUCTION AND OBJECTIVES: The mechanism of stress urinary incontinence (SUI) development likely involves incomplete regeneration of the pudendal nerve and repair of the external urethral sphincter (EUS). Electrical stimulation (e-stim) can increase brain-derived neurotrophic factor expression, activate Schwann cells, and promote neuroregeneration after nerve injury. The aim of this study was to determine if bilateral pudendal nerve e-stim would facilitate recovery from SUI in a simulated childbirth injury model. METHODS: Forty virgin Sprague-Dawley female rats (250e300g) received either sham injury or pudendal nerve crush (PNC) þ vaginal distension (VD) to establish a SUI model. Immediately after injury, electrodes were implanted at the pudendal nerve bilaterally. Each animal underwent sham e-stim, twice per week e-stim, or daily estim for 2 wk with subthreshold stimulation parameters (20Hz frequency, 0.1ms pulse duration, 0.3mA current). Two weeks after injury and treatment, each animal underwent leak point pressure (LPP) testing with EUS electromyography (EMG), and pudendal nerve sensory branch potential (PNSBP) recordings and was then euthanized for histology. RESULTS: Two wk after injury, LPP was significantly increased in both 2/wk e-stim and daily e-stim compared to sham e-stim. Daily estim significantly increased LPP compared to 2/wk e-stim. However, all stimulated groups had significantly decreased LPP compared to either sham injury with no electrode implant or sham injury with sham e-stim. EUS EMG and PNSBP were significantly decreased after injury with sham e-stim compared to either sham injury with no implant or sham injury with sham e-stim, but not with 2/wk e-stim and daily e-stim, indicating improved recovery after e-stim. Histology revealed that 2 wk after injury, density and morphology of pudendal nerve axons were significantly decreased compared to sham injury with no electrode implant, but improved after 2/wk and daily e-stim. Neuromuscular junction innervation was significantly decreased after injury, but improved after 2/wk and daily e-stim. Masson’s trichrome revealed that morphology of the EUS significantly decreased compared to sham injury, but improved with 2/wk and daily e-stim. CONCLUSIONS: This study demonstrates that chronic bilateral e-stim to the pudendal nerve is feasible and can accelerate recovery in a model of SUI. Daily e-stim provides better preservation of urethral function than twice per week e-stim.

Aims α1-blockers improve voiding symptoms through the reduction of prostatic and urethral smooth muscle tone; however, the underlying mechanism of improvement of storage symptoms is not known. Using a rat model of detrusor overactivity caused by cerebral infarction (CI), we undertook the present study to determine whether the effect of an α1-blocker, naftopidil, is dependent on the suppression of C-fiber afferents. Methods To induce desensitization of C-fiber bladder afferents, we injected resiniferatoxin (0.3 mg/kg, RTX) sub-cutaneously to female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO) (RTX-CI rats). As controls we used rats without RTX treatment (CI rats). MCAO and insertion of a polyethylene catheter through the bladder dome were performed under halothane anesthesia. We investigated the effects on cystometrography (CMG) of intravenous (i.v.), intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of naftopidil in conscious CI rats. Results Bladder capacity (BC) was markedly reduced after MCAO in both RTX-CI and CI rats. I.v. administration of naftopidil significantly increased BC in CI rats without an increase in residual volume, but it had no effects on BC in RTX-CI rats. I.t. administration of naftopidil significantly increased BC in CI but not in RTX-CI rats. Conclusions These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc.

Background: The recent introduction of laparoscopic procedures has markedly altered urological surgery. Laparoscopic nephropexy has attracted the attention of urologists as a treatment for nephroptosis. Herein, we describe our experiences and quality-of-life outcome of laparoscopic nephropexy and discuss its indications and surgical techniques. Methods: From May 1998 to February 2002, six female patients, ranging in age from 20 to 64 years (median age 39.8 years), with symptomatic nephroptosis underwent laparoscopic nephropexy. Mean preoperative downward kidney displacement was 2.25 vertebral bodies (range 2–2.5) and all affected kidneys were tilted at orthostasis. One patient underwent nephropexy through the transperitoneal approach and the remaining patients underwent nephropexy through the retroperitoneal approach. To evaluate surgical results, postoperative follow-up interview (pain visual analog scale and the short-form 36 (SF-36) health survey questionnaire) and objective examinations were performed. Results: All procedures were accomplished without complication. Postoperative intravenous pyelography correctly confirmed fixed kidney in both supine and erect positions. All patients reported an improvement of symptoms approximately 1 month after nephropexy and no symptoms have recurred during the follow-up period (range 6.3–50.7 months). On the SF-36, two domains, including role limitations due to emotional problems (RE) and mental health (MH), exhibited significant improvement postoperatively (P = 0.0405 and P = 0.0351, respectively). Conclusions: Laparoscopic, in particular retroperitoneoscopic, nephropexy yields excellent outcomes and greatly improves general health-related quality of life, particularly mental status, as a minimally invasive treatment for symptomatic nephroptosis.

Percutaneous tibial nerve stimulation (TNS) has been used for the treatment of overactive bladder symptoms. The efficacy of TNS has been reported to be same as those of antimuscarinic drugs. However, currently the possible mechanisms underlying tibial neuromodulation are not fully understood. The purpose of this study is to develop an animal model for tibial neuromodulation and to investigate possible neural mechanisms underlying tibial neuromodulation.

Objectives. To evaluate the clinical efficacy and durability of transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia. The clinical variables useful in predicting outcome were identified. Methods. From October 1996 to March 2000, 58 patients with symptomatic benign prostatic hyperplasia were treated with TUMT using the Urowave device. Treatment outcome was evaluated by the International Prostate Symptom Score (IPSS), quality-of-life assessment score, and urodynamic investigation. The patients were divided into those having a good and poor response on the basis of the degree of IPSS decrease at 3 months. Results. The mean IPSS significantly decreased from 19.2 at baseline to 13.3 at 3 months (P

Treatment for benign prostatic hyperplasia (BPH), including minimally invasive therapy, can impair the quality of life. We prospectively determined the impact of 4 different interventional therapies on quality of life and sexual function.A total of 173 patients were prospectively evaluated between February 1995 and August 1997. Treatment modalities consisted of standard transurethral resection of the prostate in 55 cases, transurethral microwave thermotherapy in 34, interstitial laser coagulation of the prostate in 42 and transurethral needle ablation in 42. Disease specific quality of life was assessed using the International Prostate Symptom Score quality of life assessment index and BPH impact index. In addition, a self-reporting questionnaire was completed before and 3 months after treatment to determine the impact on sexual function.All 4 treatment groups showed significant improvement in the symptom score, International Prostate Symptom Score quality of life assessment score and BPH impact index score. Satisfaction with treatment was highest in patients treated with transurethral resection or laser coagulation. A mild to moderate decrease in erectile function was noted in 26.5%, 18.2%, 18.4% and 20.0% of the transurethral resection, microwave thermotherapy, laser coagulation and needle ablation groups, respectively, but there was no significant difference of mean pretreatment and posttreatment erectile function or libido scores in any group. Ejaculation loss or severe decrease in ejaculate volume was reported by 48.6%, 28.1%, 21.6% and 24.3% of the patients, respectively. Interestingly, 20 of the 44 patients (45. 5%) with loss of ejaculation or severe decrease in ejaculate reported deterioration of the sex life, while only 2 (3.6%) of the 56 without any change in ejaculate volume reported such deterioration. The association of ejaculatory dysfunction with an adverse impact on sexual activity was highly significant (p0.0001).Significant improvement in quality of life could be achieved with the present assessed interventional therapies. There was no significant change in sexual desire or erectile function with these therapies. Posttreatment sexual dysfunction appears to be mainly related to impaired ejaculatory function. Urologists should provide proper counseling regarding the possibility of this complication even in patients receiving minimally invasive treatment.

The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia. A catheter was inserted into the bladder via the bladder dome for saline infusion. A cuff electrode was placed around right tibial nerve for stimulation. TNS (5 Hz, 0.2 msec pulse width) at 2–4 times the threshold (T) intensity for inducing a toe movement was applied either during slow (0.08 mL/min) infusion of the bladder or for 30 min with an empty bladder. TNS had no effect on the micturition reflex when it was applied during slow bladder infusion. However, the 30‐min TNS applied with an empty bladder induced poststimulation inhibition and significantly (P < 0.05) increased the bladder capacity to about 140% of prestimulation level in a 50‐min period following the termination of stimulation. The bladder compliance was also significantly (P < 0.05) increased after the 30‐min TNS. These results suggest that different mechanisms might exist in acute‐ and post‐TNS inhibition of micturition reflex. The animal model developed in this study will be very useful for further investigations of the neurotransmitter mechanisms underlying tibial neuromodulation of bladder function., This study suggests that different mechanisms might exist in acute‐ and poststimulation tibial inhibition of the micturition reflex. The animal model developed in this study is very useful for further investigations of the neurotransmitter mechanisms underlying tibial neuromodulation of bladder function.

The purpose of this study was to determine whether duloxetine [a serotonin (5-HT)-norepinephrine reuptake inhibitor] combined with transcutaneous foot stimulation or WAY-100635 (a 5-HT1A antagonist) can enhance inhibition of bladder overactivity in cats. Cystometrograms were performed on eight cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, foot stimulation (5 Hz) was applied via transcutaneous pad electrodes to the right hindfoot at two and four times the threshold intensity for inducing a toe twitch. Duloxetine (0.003–3 mg/kg) was administered intravenously to determine the effect of combination treatment. After the 3 mg/kg dose of duloxetine, WAY-100635 (0.5 mg/kg) was given intravenously. AA irritation significantly ( P < 0.0001) reduced bladder capacity to 42.7 ± 7.4% of the saline control capacity. Foot stimulation alone at both two and four times the threshold intensity significantly ( P < 0.0001) inhibited bladder overactivity and increased bladder capacity to 66.7 ± 6.3% and 85.7 ± 6.5% of the saline control, respectively. Duloxetine alone dose dependently inhibited bladder overactivity and completely restored bladder capacity to the saline control (109 ± 15.5%) at 3 mg/kg. Although duloxetine combined with foot stimulation did not further enhance inhibition, WAY-100635 (0.5 mg/kg) given after 3 mg/kg duloxetine further increased ( P = 0.008) bladder capacity to 162.2 ± 22.5% of the saline control. Although duloxetine and foot stimulation independently inhibited bladder overactivity, combined treatment did not enhance inhibition. Duloxetine combined with WAY-100635, however, synergistically enhanced bladder inhibition, indicating a potential novel treatment for overactive bladder if duloxetine is combined with a 5-HT1A receptor antagonist drug.

In the present study, the role of 5-HT3receptors in pudendal neuromodulation of bladder activity and its interaction with opioid receptors were investigated in anesthetized cats. The bladder was distended with either saline to induce normal bladder activity or with 0.25% acetic acid (AA) to induce bladder overactivity. Pudendal afferent nerves were activated by 5-Hz stimulation at multiples of the threshold (T) intensity for the induction of anal twitching. AA irritation significantly reduced bladder capacity to 16.5 ± 3.3% of saline control capacity, whereas pudendal nerve stimulation (PNS) at 1.5–2 and 3–4 T restored the capacity to 82.0 ± 12% ( P = 0.0001) and 98.6 ± 15% ( P < 0.0001), respectively. Cumulative doses (1–3 mg/kg iv) of ondansetron, a 5-HT3receptor antagonist, eliminated low-intensity (1.5–2 T) PNS inhibition and reduced high-intensity (3–4 T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5–2 and 3–4 T significantly increased bladder capacity to 173.2 ± 26.4% ( P = 0.036) and 193.2 ± 22.5% ( P = 0.008), respectively, of saline control capacity, but ondansetron (0.003–3 mg/kg iv) did not alter PNS inhibition. Ondansetron (0.1–3 mg/kg) also significantly ( P < 0.05) increased control bladder capacity (50–200%) during either AA irritation or saline distention. In both conditions, the effects of low- and high-intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg iv) significantly ( P < 0.05) decreased control bladder capacity (40–70%) during either AA irritation or saline distention but failed to affect PNS inhibition. This study revealed that activation of 5-HT3receptors has a role in PNS inhibition of bladder overactivity. It also indicated that 5-HT3receptor antagonists might be useful for the treatment of overactive bladder symptoms.

The role of 5-HT2 and opioid receptors in pudendal inhibition of bladder activity induced by intravesical infusion of saline or 0.25% acetic acid (AA) was investigated in anesthetized cats using methysergide (a 5-HT2 receptor antagonist) and naloxone (an opioid receptor antagonist). AA irritated the bladder and significantly (P

The objective of the present study was to investigate the matrix protein of a rare urinary stone that contained calcium carbonate. A urinary stone was extracted from a 34-year-old male patient with metabolic alkalosis. After X-ray diffractometry and infrared analysis of the stone, proteomic analysis was carried out. The resulting mass spectra were evaluated with protein search software, and matrix proteins were identified. X-ray diffraction and infrared analysis confirmed that the stone contained calcium carbonate and calcium oxalate dihydrate. Of the identified 53 proteins, 24 have not been previously reported from calcium oxalate- or calcium phosphate-containing stones. The protease inhibitors and several proteins related to cell adhesion or the cytoskeleton were identified for the first time. We analyzed in detail a rare urinary stone composed of calcium carbonate and calcium oxalate dihydrate. Considering the formation of a calcium carbonate stone, the new identified proteins should play an important role on the urolithiasis process in alkaline condition.

INTRODUCTION AND OBJECTIVES: The goal of this video is to present a streamlined approach to laparoscopic abdominal sacralcolpopexy. In light of the FDA warnings regarding transvaginal mesh placement and the withdrawal of transvaginal mesh kits from the marketplace, patients are seeking alternative minimally invasive options to address vaginal prolapse. The open abdominal sacralcolpopexy technique has stood the test of time and consistently delivers 95% success rates with tolerable complication rates and specifically, very low mesh complication rates. Translating the open approach to the laparoscopic approach has been made possible with modern technology. METHODS: A compendium of cases by one surgeon is presented in video format to illustrate the main technical points of the procedure. These include: port placement, dissection planes, mesh attachment to vaginal vault and to sacral promontory, and mesh coverage. A novel new vaginal manipulator specifically designed for this procedure will also be shown. RESULTS: Use of a novel new vaginal manipulator facilitates dissection of the vaginal vault and makes it easier to perform intracorporal laprascopic suturing without the need for expensive robotic technology. CONCLUSIONS: Laparoscopic abdominal sacral colpopexy is feasible and safe and can be performed within a reasonable time frame with few complications, by surgeons who are comfortable with other laparoscopic procedures.

Although simple renal cysts are common in older patients, little is known concerning their natural history. We examined the natural history of renal cysts by investigating the prevalence and sequential changes in their size and number in individuals.We collected data on 14,314 individuals who participated in a multiphasic health screening program at our institute in 1999. An ultrasound renal cyst prevalence survey was performed. As a longitudinal study, 45 patients with renal cysts were followed a mean of 6 years from January 1993 to December 1999.In the prevalence survey 1,700 individuals (11.9%) had at least 1 renal cyst on ultrasound. The ratio of men-to-women with cysts was 2:1. The prevalence of renal cysts increased more than 7-fold with age from 5.1% in the fourth to 36.1% in the eighth decade of life. Our longitudinal study revealed that the majority of cysts increased in size and number. The average increase in size and the rate of enlargement were 2.82 mm. and 6.3% yearly, respectively. Cysts in patients younger than 50 years grew more rapidly than those in patients 50 years old and older, at a rate of 3.94 and 1.84 mm. yearly, respectively (p = 0.010). Multiloculated cysts progressed more rapidly than simple cysts (6.93 versus 2.18 mm. yearly, p0.0001).The prevalence of renal cysts increases with age and shows a remarkable difference in incidence by sex. Renal cysts progress in size and number, and appear to grow more rapidly in younger patients. The natural history of multiloculated cysts may be distinct from that of simple cysts and warrants further investigation.

Migration of an intrauterine contraceptive device (IUCD) into the bladder and secondary stone formation are uncommon complications associated with the insertion of IUCD. To our knowledge, there have been no such reported cases in Japan. In the present report, we describe the case of a 59-year-old woman who underwent an operation for the removal of an IUCD from the bladder, which had been inserted 30 years ago. The patient was referred to our facility because of hematuria and recurrent urinary tract infections. A plain film revealed a calcified mass in the pelvis, and cystoscopy revealed a fully mobile calculus in the bladder. During a transurethral cystolithotripsy, the IUCD was found within the calculus and removed transurethrally. No fistulae or defects were found in the bladder wall.

A 58-year-old woman presented to our emergency room with cystitis-like symptoms and macroscopic hematuria. Her symptoms were improved by the administration of an antibiotic, but transabdominal ultrasonography revealed a mass in her pelvis. The pelvic magnetic resonance imaging (MRI) depicted a solid tumor in the retropubic space. The patient requested hasty surgical excision of the tumor, rather than the conservative treatment after the diagnosis by cytology and biopsy. The postoperative histopathological examination revealed nodular fasciitis. She has been followed up for 8 months without any evidence of local recurrence. Nodular fasciitis is a mesenchymal lesion of proliferated fibroblast and commonly occurs in the subcutaneous tissue of the extremities. Frequently, it resembles a sarcoma, but it is said to be a benign disorder. In the urological domain, 14 intravesical cases have been reported. To our knowledge, this is the first case of the nodular fasciitis arising in the pelvis. We report this case and discuss the literature.

To clarify the effects of zolpidem, a gamma-aminobutyric acid (GABA)(A) receptor agonist, on bladder function, and urine production, we investigated the effects of zolpidem administration on bladder overactivity induced by cerebral infarction (CI) and on urine excretion increased by water overloading in Wistar rats.CI was induced by left middle cerebral artery occlusion. The effects on bladder function of zolpidem alone or in combination with the GABA(A) receptor antagonist bicuculline, were then examined in the CI rats using cystometry. The antidiuretic effect of zolpidem was investigated in water-loaded and Brattleboro rats (genetically vasopressin-deficient). Blood samples were collected from water-loaded rats to determine the aldosterone level 1 and 6 hr after zolpidem administration.Zolpidem increased bladder capacity dose-dependently, but had no significant effect on bladder contraction pressure in CI rats. Bicuculline dose-dependently inhibited zolpidem-induced increases in bladder capacity without affecting bladder contraction pressure. Zolpidem dose-dependently decreased the volume of urine excreted in water-loaded and Brattleboro rats. Compared with the control group, zolpidem significantly increased the aldosterone concentration in the plasma of water-loaded rats 1 hr after administration.Zolpidem increased bladder capacity via a GABAergic mechanism in CI rats, and suppressed urine excretion via a pathway that was not through activation of vasopressin V(2) receptors in water-loaded and Brattleboro rats. These results suggest that zolpidem may improve nocturia via an increase in bladder capacity and a decrease in urine excretion.

Increase in bladder mucosal permeability can be reproduced by intravesical administration of protamine sulfate (PS); however, the influence of PS once administered into the bladder disappears within several days. We developed a chronic animal model of urothelial injury using PS. Insertion of a polyethylene catheter through the bladder dome was performed in female Wistar rats. The other end of the catheter was connected to an osmotic pump for continuous delivery of PS or vehicle for 2 wk. Urinary frequency (UF) and voided volume (VV) were measured in the metabolic cage. The fifth group of rats received a high dose of PS (10 mg/ml) for 2 wk and were followed for a further 2 wk without PS. The sixth group received a high dose of PS for 2 wk and loxoprofen (0.1 mg·kg−1·day−1) for 4 wk. UF was increased, and VV was reduced in rats treated with a high dose of PS but not changed in rats treated with a vehicle or a low dose of PS (1 mg/ml). UF was further increased in the fifth group, while unchanged in the sixth group. Histological sections in rats treated with a high dose of PS demonstrated a loss of the upper layer of urothelial cells and an increased number of mast cells. PGE2 level in the bladder was significantly elevated in the fifth group. These results indicate that chronic urotherial injury leads to an increase in UF and a decrease in VV. Increased PGE2 level in the bladder is likely to be associated with long-lasting storage dysfunction.

Muscarinic receptor antagonists are used clinically for their therapeutic peripheral effects on bladder function. However, these agents may also act on central muscarinic receptors, especially in individuals with compromised blood–brain barrier function. We compared the effects of atropine and tolterodine, agents that do and do not readily cross the blood–brain barrier, respectively, administered peripherally (intravenous [i.v.]) and centrally (intracerebroventricular [i.c.v.]) on cystometrography in conscious rats after cerebral infarction induced by middle cerebral artery occlusion or sham surgery. We hypothesized that tolterodine would produce greater improvement in bladder capacity and less impairment in bladder contractility and that the effects of both agents would be greater in rats with cerebral infarction and sham-operated rats after peripheral administration, but that tolterodine and atropine would exert similar effects after central administration. Bladder capacity was markedly reduced following cerebral infarction. Low-dose i.v. tolterodine (≤ 20 nmol/kg) significantly reversed this effect without altering residual volume or bladder contraction pressure. Low-dose i.v. atropine (2 nmol/kg) had no effect on bladder capacity but significantly decreased bladder contraction pressure. Higher doses of i.v. atropine (≥ 20 nmol/kg) significantly increased bladder capacity but also significantly increased residual volume and decreased bladder contraction pressure. Tolterodine was significantly more efficacious than atropine in increasing bladder capacity, whereas atropine produced significantly greater increases in residual volume and reductions in bladder contraction pressure; these treatment group differences were also observed in sham-operated animals. Tolterodine and atropine administered i.c.v. significantly increased bladder capacity following cerebral infarction or sham surgery; however, this was accompanied by significantly increased residual volume and decreased bladder contraction time. The decrease in bladder contraction time was significantly smaller after tolterodine vs atropine. Peripherally acting muscarinic receptor antagonists may be preferable to centrally acting agents for minimizing adverse events, such as incomplete bladder emptying, even in individuals with compromised blood–brain barrier function.

The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity.Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON.Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P0.05). In decerebrated rats, low dose of DON did not change micturition parameters.These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

We report our experience with interstitial laser coagulation of the prostate (ILCP) using an Indigo 830j diode laser system for benign prostatic hyperplasia (BPH). From March 1998 to November 2000, we treated 45 patients between 51 and 95 years old (average 71.5) with symptomatic BPH. The mean prostatic volume before ILCP was 62.0 cm3. We experienced no serious complications. Three months after ILCP, the mean international prostate symptom score (I-PSS) quality of life (QOL) index and post-void residual volume (PVR) decreased significantly from 18.0 to 9.2, from 4.4 to 2.1 and from 103.6 ml to 44.5 ml, respectively. The mean maximum flow rate (MFR) increased from 7.6 ml/sec at baseline to 9.2 ml/sec 3 months after ILCP, but the difference was not statistically significant. Before and after ILCP, 8 patients were available to evaluate pressure-flow study data. The detrusor pressure at the maximum flow rate decreased significantly from 118.3 cmH2O at baseline to 78.6 cmH2O 3 months after ILCP. The improvement of the I-PSS, QOL index, MFR and PVR continued and at 24 months reached 5.7, 1.8, 11.6 ml/sec and 54.6 ml, respectively. In our assessment of the questionnaire addressing the patient's satisfaction after the treatment, the majority of the patients who answered the questionnaire were pleased with the results of ILCP. We assessed the relation of the overall treatment efficacy with the number of punctures and the total amount of the laser energy delivered, but we did not find any relation. Our clinical results suggest that the ILCP using Indigo 830j is an effective modality and the short-term treatment efficacy is favorable.