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Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP.Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI)0.33 (NPI33) and nocturnal urine production90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup.A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%).This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

INTRODUCTION AND OBJECTIVE:To assess the prevalence of nocturnal polyuria (NP) in a large epidemiologic study of a US population-representative sample of men (M) and women (W) ≥30 years (The EpiNP ...

INTRODUCTION AND OBJECTIVES:In men, overactive bladder (OAB) symptoms commonly overlap with those of benign prostatic hyperplasia (BPH), but limited data are available on the use of OAB medications...

These are the final results of the prospective, multicenter, long-term (3.5-year) study of the efficacy/safety of onabotulinumtoxinA for overactive bladder syndrome.Patients who completed either of 2, 24-week phase 3 trials could enter a 3-year extension and continue treatment with onabotulinumtoxinA 100 U as needed to control overactive bladder symptoms. Data were analyzed by the treatment(s) received (up to 6) and in discrete subgroups that received 1, 2, 3, 4, 5 or 6 treatments (to evaluate the consistency of the response after repeat treatments in the same patient groups). Assessments included the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients who reported improvement/great improvement in urinary symptoms on the TBS (Treatment Benefit Scale) at week 12 as co-primary end points. Other end points were the change from baseline in I-QOL (Incontinence Quality of Life), the number of urgency and micturition episodes per day; duration of effect; the number of adverse events; and the initiation of intermittent catheterization.Consistent mean reductions in urinary incontinence were observed following continued onabotulinumtoxinA treatment, ranging from -3.1 to -3.8 in the overall population and -2.9 to -4.5 in the discrete subgroups. Durable improvements were seen in overactive bladder symptoms and quality of life. A high proportion of patients rated their condition as improved/greatly improved. The median duration of effect was 7.6 months. The most common adverse event was urinary tract infection. The rate of de novo catheterization after the first treatment was 4.0% and it ranged from 0.6% to 1.7% after subsequent treatments.Long-term onabotulinumtoxinA treatment consistently decreased overactive bladder symptoms and improved quality of life with no new safety signals.

Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation.Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes. A total of 40 immunocompetent full-thickness abdominal wall defect rabbit models were used, including 8 in each of the poly-L-lactic acid, polyurethane, polyvinylidene fluoride and polypropylene experimental groups, and sham controls. Two 20 mm defects were created per animal and primarily repaired. The experimental groups then underwent onlay of each repair material while sham controls did not. Four rabbits per group were sacrificed at days 30 and 90. Abdominal wall specimens containing the defect with or without repair material were explanted to be assessed by histology (hematoxylin and eosin staining, and immunohistochemistry) and biomechanical testing at 30 and 90 days.At 90 days of implantation tissues repaired with all 4 materials showed biomechanical properties without significant differences. However, polypropylene and polyvinylidene fluoride meshes demonstrated a sustained chronic inflammatory response profile by 90 days. In contrast, poly-L-lactic acid and polyurethane meshes integrated well into host tissues with a decreased inflammatory response, indicative of constructive remodeling.Poly-L-lactic acid and polyurethane alternative materials achieved better host integration in rabbit models than current synthetic repair materials.

We evaluated the efficacy, safety and tolerability of the EP1 receptor antagonist ONO-8539 in patients with overactive bladder syndrome.This was a 12-week, randomized, double-blind, placebo controlled, parallel group, multicenter study with a 2-week single blind placebo run-in phase. The 435 patients were randomized to receive twice daily ONO-8539 (30, 100 or 300 mg), placebo or once daily tolterodine (4 mg).At the end of the 12-week treatment no statistically significant difference was found between ONO-8539 and placebo in the change from baseline in the number of micturitions per 24 hours. The primary end points for 30, 100 and 300 mg ONO-8539, and placebo were -1.02, -1.53, -1.31 and -1.40, respectively. There was no statistically significant difference between any ONO-8539 group and placebo in the change from baseline in the number of urgency or urinary urgency incontinence episodes per 24 hours, or the mean volume voided per micturition, which were secondary end points. Statistically significant differences for tolterodine vs placebo were observed in the change from baseline in the number of micturitions (p = 0.045), urgency episodes (p = 0.04) and mean volume voided per micturition (p0.001). The incidence of adverse events was 54.1% in the placebo group, 43.0% to 54.0% in the ONO-8539 groups and 46.6% in the tolterodine group. The intensity of adverse events was similar among the treatment groups. Similar to other treatments, the most frequently reported adverse events after ONO-8539 were nasopharyngitis and diarrhea.The results of this study, which to our knowledge represents the first evaluation of ONO-8539 in patients with overactive bladder, suggest a minimal role for EP1 receptor antagonism in the management of overactive bladder syndrome.

The 6th International Consultation on New Developments in Prostate Cancer and Prostate Diseases met from June 24-28, 2005 in Paris, France to review new developments in benign prostatic disease. A series of committees were asked to produce recommendations on the evaluation and treatment of lower urinary tract symptoms in older men. Each committee was asked to base recommendations on a thorough assessment of the available literature according to the International Consultation on Incontinence level of evidence and grading system adapted from the Oxford system. The Consultation endorsed the appropriate use of the current terminology lower urinary tract symptoms/benign prostatic hyperplasia/benign prostate enlargement and benign prostatic obstruction, and recommended that terms such as "clinical benign prostatic hyperplasia" or "the benign prostatic hyperplasia patient" be abandoned, and asked the authorities to endorse the new nomenclature. The diagnostic evaluation describes recommended and optional tests, and in general places the focus on the impact (bother) of lower urinary tract symptoms on the individual patient when determining investigation and treatment. The importance of symptom assessment, impact on quality of life, physical examination and urinalysis is emphasized. The frequency volume chart is recommended when nocturia is a bothersome symptom to exclude nocturnal polyuria. The recommendations are summarized in 2 algorithms, 1 for basic management and 1 for specialized management of persistent bothersome lower urinary tract symptoms. The use of urodynamics and transrectal ultrasound should be limited to situations in which the results are likely to benefit the patient such as in selection for surgery. It is emphasized that imaging and endoscopy of the urinary tract have specific indications such as dipstick hematuria. Treatment should be holistic, and may include conservative measures, lifestyle interventions and behavioral modifications as well as medication and surgery. Only treatments with a strong evidence base for their clinical effectiveness should be used

Purpose: We analyzed the adverse event profile, long-term efficacy and cost-effectiveness of transurethral needle ablation of the prostate for lower urinary tract symptoms associated with benign prostatic hyperplasia as an alternative to transurethral resection of the prostate in men with symptoms uncontrolled by medical therapy.Materials and Methods: A total of 71 men on a waiting list for transurethral resection of the prostate after failed medical therapy underwent transurethral needle ablation of the prostate. Symptom scores, uroflowmetry and residual urine were measured before and up to 10 years following treatment. Transrectal ultrasound and pressure flow studies were performed before, and 3 and 12 months following treatment, respectively. Treatment failure was defined as lower urinary tract symptoms progression requiring further therapy or associated with deteriorating quality of life assessment.Results: Apart from transient postoperative urinary retention, no significant treatment emergent adverse...

retinol binding prot. (RBP1), myosin heavy chain 10 and 11 (MYH10, MYH11), smoothelin (SMTN), aSMC actin (ACTA2), Rho kinase (ROCK1) and (ROCK2), Collagen I and III, Myocardin and Osteopontin. RESULTS: Analysis of spotting experiment showed significantly more urine spots with smaller volume in PNI compared to sham. Sham animals had regular micturition cycles, whereas bladder contractions were absent in PNI with overflow incontinence occurring during bladder filling. Maximal responses to carbachol were decreased in PNI bladder tissue compared to sham. PNI bladders showed reduced expression of SMTL (p 0,05) and Osteopontin (p

Purpose: We investigated the presence and functional role of β-adrenoceptor subtypes in the bladder base and proximal urethra of the female pig.Materials and Methods: Saturation experiments were done with 7 concentrations (0.25 to 16 nM.) of [3H]-dihydroalprenolol (NEN Life Science Products, Boston, Massachusetts). Competition experiments with [3H]-dihydroalprenolol were performed with unlabeled antagonists (β1 selective CGP20712A, β2 selective ICI118551 and β3 selective SR59230A). In functional studies concentration-relaxation curves to the β3-agonist BRL37344 were obtained and antagonist affinities for SR59230A were determined.Results: CGP20712A displaced [3H]-dihydroalprenolol with low affinity, suggesting that β1-adrenoceptors were not present. Displacement with ICI118551 in the bladder base and urethra best fitted a 2-site model with 20% and 28% high affinity sites (β2), respectively. Displacement experiments with SR59230A in the bladder base demonstrated that 59% of binding sites had high af...

We investigated the characterization of muscarinic receptor subtypes in the female pig urethra.The affinities of muscarinic antagonists against carbachol responses were calculated in normal and cyclic adenosine monophosphate (cAMP) elevated tissues (contraction with KCl and relaxation with isoprenaline) using longitudinal and transverse strips of urethra.In displacement experiments with 1-quinuclidinyl [phenyl-4-3H] benzilate inhibitory constant (pKi) values of 4-diphenylacetoxyl-N-methyl-piperidine methiodide (DAMP) M3 selective antagonist) and methoctramine (M2 antagonist) indicated the presence of the M2 receptor. In functional studies contraction responses to carbachol were greater in longitudinal than in circular muscle. After cAMP elevation the contraction response increased in circular muscles to the level close to that of longitudinal muscles but did not change significantly in cAMP elevated longitudinal muscle. On normal circular tissues 4-DAMP had high mean affinity (mean apparent pKB value 9.3) but with a Schild slope of less than unity (0.76). Methoctramine competitively antagonized carbachol responses (mean affinity [pA2] value 6.9). On normal longitudinal tissues 4-DAMP and methoctramine competitively antagonized carbachol responses (mean pA2 9.0 and 6.2, respectively). After cAMP elevation in circular tissues mean pA2 values for 4-DAMP (8.7) were significantly lower (p = 0.0015), and those for methoctramine (7.3) were significantly higher (p = 0.0193) than in normal tissues. In longitudinal tissues the mean pA2 value for methoctramine (6.9) was significantly greater than in normal tissues (p0.0001) but the value for 4-DAMP (8.8) did not alter.Pig urethra appears to have predominantly M2 muscarinic receptors. Contraction of the normal urethra appears to be predominantly mediated by M2 and M3 receptors in circular muscle but by M3 receptors in longitudinal muscle. After cAMP elevation a contribution to contraction of M2 receptors appeared to be demonstrated in the 2 tissues but the involvement of M2 receptors appeared greater in circular muscle.

Purpose: We compared ambulatory urodynamics and conventional video cystometry findings in women with symptoms of bladder overactivity.Materials and Methods: In a prospective randomized crossover study 106 women with symptoms of urinary urgency with or without incontinence were comprehensively investigated by video cystometry and ambulatory urodynamics in random order. In addition, all women completed a validated symptoms questionnaire and voiding diary.Results: Involuntary detrusor activity was detected in 32 and 70 cases on video cystometry and ambulatory urodynamics, respectively (p

Purpose: We prospectively studied the potential contribution of ambulatory urodynamic monitoring in men with urinary symptoms unable to initiate a void on conventional video cystometrography. Materials and Methods: A total of 40 consecutive symptomatic men with a median International Prostate Symptom Score of 19 (range 1 to 29) and median age of 51.9 years (range 30 to 75) who were unable to void during video cystometrography underwent ambulatory urodynamic monitoring. Solid-state transducers mounted on silicone coated catheters were inserted urethrally and rectally, and connected to a portable recorder. Subjects voided in private into a specially designed flow meter, which they connected to the recording device. Results: Of the patients 2 (5%) failed to attend ambulatory urodynamic monitoring, despite multiple reminders, and in 1 (2.5%) the trace was uninterpretable. Pressure flow data were available for the remaining 37 patients with mean plus or minus standard deviation 2.72 ± 0.1 storage void cycles recorded per patient. All 6 patients (15%) with obstruction were older than 40 years. In 6 cases (15%) obstruction was equivocal and the remainder were unobstructed. Transurethral prostatic resection in 2 and urethrotomy in 1 of 6 patients with obstruction resulted in subjective and objective improvement. Conclusions: The bashful bladder syndrome was not associated with any specific urodynamic diagnosis. Ambulatory urodynamic monitoring will yield a urodynamic diagnosis in more than 90% of cases after failure to record void data on video cystometrography. A surgically correctable cause of symptoms can be found in about 20% of men older than 40 years. The contribution of ambulatory urodynamic monitoring compared to more conventional evaluation in men younger than 40 years is negligible.

All urethral reconstruction that involves substitution has an inherent ongoing incidence of restenosis with time. Anastomotic restoration of urethral continuity naturally obviates these complications but to achieve its potential of a long-term stricture-free success rate that approaches 100% circumstances must be ideal and the reconstructive surgical technique must be meticulous. If the critical indications for anastomotic reconstruction are overextended, complications inevitably increase. Considerable additional urethral length is required to overcome the terminal atretic deficiency associated with hypospadias and create a tension-free anastomotic neomeatoplasty. Mobilization and advancement of the penile urethra alone are rarely sufficient to achieve this without causing penile chordee. We describe the details of bulbar elongation anastomotic meatoplasty (BEAM) that we have been using for approximately the last 8 years.The only part of the urethra that can be mobilized to provide extra length for anastomotic urethroplasty without creating penile curvature chordee is the bulbar urethra. Full length mobilization of the whole length of the bulbar urethra through a perineal incision provides 2 to 2.5 cm. of tension-free lengthening in children and 4 to 5 cm. in adults. Thus, many subterminal urethral deficiencies can be resolved by bulbar elongation anastomotic meatoplasty when the total extent of the urethral deficiency is not disproportionally long. We performed bulbar elongation anastomotic meatoplasty in 12 patients 2 to 25 years old.At a followup of 2 to 7 years the neomeatus is functionally and cosmetically satisfactory in all cases with no long-term complications or chordee.When circumstances are appropriate, bulbar elongation anastomotic meatoplasty is a preferable alternative to some of the current substitution procedures. Once established, anastomotic reconstructions are generally stable in the long term.

Kari Tikkinen*, Hamilton, Canada; Rufus Cartwright, London, United Kingdom; Anna Kirby, San Diego, CA; Altaf Mangera, Sheffield, United Kingdom; Gans Thiagamoorthy, London, United Kingdom; Prabhakar Rajan, Glasgow, United Kingdom; Jori Pesonen, Tampere, Finland; Tom Palmer, Bristol, United Kingdom; Chris Ambrose, Vik Khullar, Andrew Walley, Marjo-Riitta Jarvelin, Phillip Bennett, London, United Kingdom; Chris Chapple, Sheffield, United Kingdom

Anna Kirby*, San Diego, CA; Rufus Cartwright, London, United Kingdom; Kari Tikkinen, Hamilton, Canada; Tom Palmer, Bristol, United Kingdom; Gans Thiagamoorthy, London, United Kingdom; Prabhakar Rajan, Glasgow, United Kingdom; Jori Pesonen, Tampere, Finland; Andrew Walley, London, United Kingdom; Altaf Mangera, Sheffield, United Kingdom; Georgios Grigoriadis, Chris Ambrose, Marjo-Riitta Jarvelin, Phillip Bennett, London, United Kingdom; Chris Chapple, Sheffield, United Kingdom; Vik Khullar, London, United Kingdom

IN this issue of the Journal Mikami et al (page 1882) describe the fabrication of tissue engineered (TE) oral mucosa. The use of TE oral mucosa provides a means of reducing the morbidity of the procedure in patients with lengthy strictures, for which large amounts of graft are required for augmentation or substitution urethroplasty. Clearly any such graft material must have cellular line stability and adequate intrinsic strength, acquire an adequate blood supply, and prove to be durable and resistant to fibrosis. In addition, the graft cellular type should be resistant to any underlying disease process such as lichen sclerosis, as is seen with oral mucosa. In particular it is important to keep in mind that the underlying disease process seen with true strictures compared to traumatic injuries of the urethra is one of ischemic spongiofibrosis. Therefore, the underlying graft bed is sometimes far from optimal and, thus, difficult to duplicate in an experimental setting by producing an acute urethral injury. Nevertheless, we acknowledge the importance of animal models such as that reported by Mikami et al.

Eighty patients with prostatic obstruction were entered into a double-blind parallel study of prazosin versus placebo. There were 25 withdrawals or exclusions, leaving 55 patients for analysis. Mean maximum flow rates increased significantly more in patients treated with prazosin than in those treated with placebo (P less than 0.005), but there was no significant reduction in maximum voiding pressure. The mean number of voids, recorded on diary cards, was reduced from an initial 10.0/24 h by 2.1 in the final week, a significantly greater reduction than in the placebo group (P less than 0.01). However, there were no statistically significant changes in the filling cystometrograms. When patients were classified as responders or non-responders in terms of bladder filling, urine flow, bladder emptying, weekly average of voids/24 h and nocturia, the proportion of patients responding to prazosin was significantly greater in all categories except bladder filling and emptying. It was concluded that prazosin at a dose of 2 mg bd is a safe and effective treatment for prostatic obstruction and may be used in patients awaiting surgery and those who are unfit for operation.