Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients

PURPOSE: The 2 prominent features of interstitial cystitis are pain and increased numbers of mast cells in the bladder. In this pilot study we determined the concentration of soluble mediators associated with activation of sensory neurons and/or mast cells that were present in the urine. MATERIALS AND METHODS: The study groups included 4 interstitial cystitis patients, 7 kidney donors with no history of bladder disease as negative controls, 6 bladder cancer patients and 7 patients with urinary tract infection as reference controls. Urine samples were assayed for different soluble mediators using immunoassays for tryptase (a marker for mast cell activation), neurotrophic factors (markers of neuronal plasticity) and chemokines (markers of inflammatory cell activity). Results were normalized based on creatinine concentration. RESULTS: There was a marked increase in the average amounts of tryptase and 3 neurotrophic factors in patient urine. Interestingly, the mediator profile in the urine of bladder cancer patients was indistinguishable from that of interstitial cystitis patients with respect to these same 4 proteins. There was no difference between normal control and urinary tract infection urine samples. CONCLUSIONS: These findings may account for several clinical and pathological features found in interstitial cystitis and bladder cancer. Although preliminary due to the limited numbers of patients, they also suggest that increased levels of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor and tryptase in the urine could serve as a basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.     

Urodynamic factors influence the duration of Escherichia coli bacteriuria in deliberately colonized cases

PURPOSE: We evaluated the influence of urodynamic factors on the establishment of bacteriuria, after deliberate intravesical inoculation with Escherichia coli. MATERIALS AND METHODS: Nine women and 7 men with recurrent symptomatic urinary tract infections underwent intravesical injection of E. coli 83972. This strain had documented ability to persist in the urinary tract and it lacks expressed virulence factors associated with urinary tract infection. RESULTS: Successful long-term colonization (5 months to 3 years) was achieved in 6 of 12 patients with neurogenic bladder disorder, including normal or high bladder capacity, normal or low detrusor pressure and residual urine. Short-term bacteriuria (13 days) occurred in 1 but long-term bacteriuria was not established in the 4 patients with normal lower urinary tract function. Occasionally urine samples from the colonized patients contained other bacterial strains, which cleared spontaneously except for a Klebsiella strain that became established in 2 and subsequently eliminated E. coli 83972. CONCLUSIONS: E. coli 83972 bacteriuria could only be established in a subset of patients with defective bladder voiding, suggesting that urodynamic defects permit a nonvirulent strain to establish in the urinary tract, but that additional host factors determine if bacteriuria will persist.     

Intravesical electromotive drug administration technique: preliminary results and side effects

PURPOSE: We performed intravesical electromotive drug administration (EMDA) for various bladder disorders during a 3-year period and assessed the technique, possible applications, complications and outcomes of this procedure. MATERIALS AND METHODS: Intravesical EMDA was performed with local anesthetics for transurethral surgery and in combination with dexamethasone for the treatment of noninfectious chronic cystitis (interstitial/radiation cystitis), with mitomycin C for recurrence prophylaxis of high risk superficial bladder cancer and with oxybutynin/bethanechol for the hyperreflexive/acontractile detrusor. A standardized power source and electrode catheter were used for 215 treatments in 84 patients. RESULTS: Transurethral bladder tumor resections were pain-free in 10 of 12 patients. Of the 25 patients with chronic noninfectious cystitis 15 were free of symptoms for a mean of 6.6 months, and there was a 73% increase in mean bladder capacity from 244 before to 421 cc after EMDA. Of the 16 patients with superficial bladder cancer 9 were free of recurrence for a mean of 14.1 months. In 10 of 14 patients with acontractile detrusors urodynamic examination showed detrusor contraction during EMDA of bethanechol. There were no contractions without electric current. EMDA of oxybutynin reduced detrusor hyperreflexia. A bladder ulcer was the single severe local complication and 4.6% of patients, mainly those with chronic cystitis, reported significant post-EMDA bladder/urethral pain. Minor side effects accounted for 23% of all treatments. No systemic side effects occurred. CONCLUSIONS: Intravesical EMDA is effective and innocuous. The therapeutic concept combines the advantages of increased drug administration without systemic side effects.     

The life you save may be your own

Intravesical potassium sensitivity can readily elicit abnormal epithelial permeability responses in subjects with diseased bladder, primarily interstitial cystitis. The technique involves eliciting responses in each subject to 40 cc of plain water or 40 cc of potassium chloride solution (40 mEq per 100 cc water). The subjects are asked to rate their subjective responses 3-5 minutes after instillation of the test solution and told to compare the water and potassium. An abnormal provocation to potassium but not water is considered a positive response and a useful way to delineate people with epithelial dysfunction and loss of permeability control. On the other hand, normal subjects will not respond to either the water or potassium.     

Urological symptomatology in patients with reflex sympathetic dystrophy

PURPOSE: We determined the effect of reflex sympathetic dystrophy on lower urinary tract function. MATERIALS AND METHODS: A total of 20 consecutive patients (16 women and 4 men) with neurologically verified reflex sympathetic dystrophy was referred for voiding symptoms, including urgency, frequency, incontinence and urinary retention. No patient had had voiding symptoms before the initial trauma that induced reflex sympathetic dystrophy. Evaluation included medical history, physical examination, video urodynamic testing and cystoscopy. RESULTS: Mean patient age was 43.4 +/- 10.2 years (range 28 to 58) and mean duration of urological symptoms was 4.9 +/- 3.6 years (range 1 to 14). Urodynamic study demonstrated a mean cystometric bladder capacity of 417 +/- 182 ml. (range 120 to 700). The urodynamic diagnoses included detrusor hyperreflexia in 8 patients, detrusor areflexia in 8, sensory urgency in 3 and detrusor hyperreflexia with detrusor-external sphincter dyssynergia in 1. In 4 women genuine stress urinary incontinence was also documented urodynamically. CONCLUSIONS: Reflex sympathetic dystrophy may have a profound effect on detrusor and sphincter function.     

Prolonged bladder distension: experience in the treatment of detrusor overactivity and interstitial cystitis

Prolonged bladder distension continues to be recommended for the treatment of detrusor instability and other bladder conditions. We have reviewed our experience of the technique. A total of 45 patients have undergone 50 procedures. Only 1 of 29 patients with detrusor instability had sustained improvement. 6 of 7 patients with interstitial cystitis noted improvement, sustained in 3. All the other patients noted some improvement. There was a 20% complication rate. 33 (75%) of the living patients returned questionnaires with 27% feeling that the operation was worthwhile. We feel that prolonged distension of the bladder is unhelpful in the treatment of patients with detrusor instability. Its place in the management of patients with interstitial cystitis and irritative symptoms remains controversial. The place of simple bladder distension should be considered.     

Bowel dysfunction after bladder reconstruction

PURPOSE: Bowel function may be disturbed after intestinal segments are used in urinary reconstruction. The etiology of this condition and its incidence in different patient groups is unclear. We studied the incidence of bowel disturbance in patients who underwent bladder replacement, continent diversion, enterocystoplasty for idiopathic detrusor instability and ileal conduit diversion. MATERIALS AND METHODS: We evaluated 71 patients after ileal conduit diversion and 82 after bladder reconstruction, including clam enterocystoplasty for detrusor instability in 28, neurogenic bladder dysfunction in 26 and nonneuropathic conditions in 28. We noted the severity of symptoms, such as frequency of defecation, nocturnal diarrhea, flatus leakage, fecal urgency, fecal incontinence and explosive diarrhea, as well as quality of life. RESULTS: Of the patients who underwent bladder reconstruction 24% had symptoms of bowel dysfunction preoperatively and 42% of those who were asymptomatic preoperatively described new bowel symptoms postoperatively. These symptoms were most common and severe in 54% of patients after clam enterocystoplasty for detrusor instability compared to 26% with neuropathy, 14% with a nonneuropathic condition and 15% with an ileal conduit. Compared to those in other groups patients who underwent enterocystoplasty for detrusor instability had a significantly higher incidence of nocturnal bowel movements (18 versus less than 4%, p <0.01), flatus leakage (29 versus less than 8%, p <0.01), fecal urgency (39 versus less than 12%, p <0.001) and fecal incontinence (32 versus less than 16%, p <0.001). The length of ileum used for clam enterocystoplasty was only slightly greater than that used for ileal conduit operations (25 versus 18 cm.). Of the patients who underwent enterocystoplasty for detrusor instability 29% regretted undergoing the procedure due to subsequent bowel symptoms. CONCLUSIONS: After enterocystoplasty for detrusor instability patients are at risk of significant bowel symptoms. The development of new bowel symptoms was associated with poor patient satisfaction.     

Bladder compliance in patients with benign prostatic hyperplasia

Factors influencing bladder compliance were examined in 116 patients with benign prostatic hyperplasia (BPH), by evaluating patients' histories, response of isolated bladder strips to acetylcholine, and the effect of prostatic urethral anesthesia. Patients' age, frequency of micturition, and duration of voiding difficulty were not correlated with bladder compliance. Bladder compliance was significantly low in patients within 30 days after urinary retention, as compared with bladder compliance in patients without an episode of retention. More than 30 days after retention, however, there was a tendency toward increased bladder compliance. Restricted to patients without an episode of retention, bladder compliance in the overactive detrusor group was found to be significantly lower than in the normal group. The responses to acetylcholine of bladder strips were compared between patients with low and normal-compliance bladders. The dose-response curve of patients with low-compliance bladders did not differ from that of those with normal compliance bladders, even when patients with an episode of retention were excluded. After prostatic urethral anesthesia, a significant increase of bladder compliance was observed in patients with an overactive detrusor, while the increase was not significant in patients with a normal detrusor. Our results strongly suggest that easy irritability of the anatomically altered prostatic urethra, as well as bladder over-distension caused by urinary retention, are important factors affecting bladder compliance in BPH patients.     

The treatment of interstitial cystitis with supratrigonal cystectomy and ileocystoplasty: difference in outcome between classic and nonulcer disease

PURPOSE: Interstitial cystitis is a chronic debilitating condition that mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer type seems to respond less favorably to various conservative treatments than the classic type. Supratrigonal cystectomy with ileocystoplasty is established treatment for interstitial cystitis refractory to conservative treatment. We evaluate whether classic interstitial cystitis responds differently than nonulcer disease to subtotal bladder resection and ileocystoplasty. MATERIALS AND METHODS: We evaluated 13 patients 27 to 79 years old with interstitial cystitis who underwent supratrigonal cystectomy and ileocystoplasty due to failure to respond to conservative treatment. RESULTS: In all 10 patients with classic interstitial cystitis symptoms were relieved after ileocystoplasty. In the 3 patients with nonulcer interstitial cystitis pain remained, while the frequency of voiding somewhat decreased. In these patients trigonal resection and urinary diversion with a Kock pouch resolved the symptoms. CONCLUSIONS: Our study confirms that supratrigonal cystectomy with ileocystoplasty results in a good outcome in classic interstitial cystitis. However, this method seems to be unsuitable for nonulcer disease. Identification of the relevant subtype of interstitial cystitis is of crucial importance for selecting the appropriate method of lower urinary tract reconstruction.     

Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis

OBJECTIVE: To determine whether any histological characteristics within the detrusor in cases of early interstitial cystitis (IC) predict the subsequent development of severe symptoms due to bladder contracture. PATIENTS AND METHODS: The detrusor muscle component of bladder biopsies from 21 patients with IC was examined in sections stained with haematoxylin and eosin. Videocystometrography was performed at least 2 months after the biopsy and the patients were then followed up clinically for at least 3 years. RESULTS: The detrusor appeared normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients with biopsies confirming detrusor myopathy were significantly more likely to have hypocompliant bladders than those with normal detrusor muscle histology (P < 0.02). Over the following 3 years, six of the eight patients with detrusor myopathy developed progressively severe symptoms and required subtotal cystectomy and enterocystoplasty. None of the 13 patients without detrusor myopathy required bladder substitution. CONCLUSION: In IC, detrusor myopathy is associated with bladder hypocompliance. Patients with detrusor myopathy appear to have more severe disease and are more likely to progress to bladder contracture requiring substitution enterocystoplasty.     

The association between dental arch dimensions and occurrence of Finnish dental consonant misarticulations in cleft lip/palate children

The evaluation of cortical evoked potentials after stimulation of the vesicourethral junction shows accurate and reproducible results and offers an elegant technique for evaluation of the viscerosensory pathways in patients with lower urinary tract dysfunction. The results must be considered in context with the results of simultaneously investigated pudendal somatosensory evoked potentials and the clinical symptomatology. They are of great help (1) in differentiating between intraspinal and extraspinal lesions of the afferent pathways of the detrusor if the etiology is unknown, (2) in differentiating between neurogenic and myogenic damage to the urinary bladder, and (3) in selecting patients not suitable for intravesical electrotherapy for bladder rehabilitation.     

The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial

PURPOSE: Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure. A recent report suggested that bacillus Calmette-Guerin (BCG) may be effective in the treatment of interstitial cystitis. A randomized, prospective, double-blind, placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done. MATERIALS AND METHODS: Patients meeting the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo. Periodic questionnaires, voiding diaries and cystometrograms were obtained. A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months (range 6 to 13). Based on an exit questionnaire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better. RESULTS: A 60% BCG response rate was noted, compared to a 27% placebo response rate. Minimum voided volume and quality of life improved in the BCG group compared to placebo. Adverse events were similar in each group, mostly irritative in nature, and no significant systemic events were noted. CONCLUSIONS: Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis. Additional studies must be performed to confirm the results of this pilot study.     

Oxybutynin in the treatment of early detrusor instability after transurethral resection of the prostate

OBJECTIVE: To evaluate the symptomatic and urodynamic effects of oxybutynin in the control of irritative micturitional symptoms during the first week after transurethral resection of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Fifty-three patients (median age 67 years, interquartile range 62-72) were included prospectively in a double-blind placebo-controlled study. Pre-operatively, uroflowmetry and cystometrography (CMG) were performed, and the post-void residual volume (PVR) measured; symptoms were rated according to the Boyarski score. CMG was repeated on the first post-operative day and medication was started on the third day. Before withdrawing the catheter on the fifth day. CMG was repeated. Three days later, symptoms were evaluated according to the Boyarski score and uroflowmetry and the estimate of PVR reassessed. RESULTS: In comparison with placebo, oxybutynin significantly decreased frequency, urgency and detrusor pressure at first sensation of filling. However, oxybutynin did not lower the rate of pre-operative detrusor instability and exerted no effect on the maximal capacity of the bladder and corresponding detrusor pressure. Dryness of mouth was reported in 13% and 65% of patients receiving placebo and oxybutynin, respectively. CONCLUSION: Oxybutynin alleviates early irritative symptoms after transurethral resection of BPH, without consistently modifying bladder urodynamics.     

The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study

PURPOSE: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis. MATERIALS AND METHODS: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome. RESULTS: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis. CONCLUSIONS: The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of interstitial cystitis.     

Insufficient detrusor contractility: a urodynamic and morphologic entity in prostatism

OBJECTIVES: To analyze the urodynamic and ultrastructural characteristics of impaired detrusor contractility in patients with prostatism in comparison with lower urinary tract obstruction. METHODS: The study comprised 200 male patients (mean age 65.3 years) with prostatism submitted to a complete urodynamic study. An ultrastructural study was randomly performed in 40 patients and analyzed 600 detrusor muscle images to determine the smooth muscle cell and interstitial changes. Detrusor urodynamics were compared with the ultrastructural cell and interstitial changes of the bladder smooth muscle. RESULTS: Urinary symptoms or free flowmetry alone failed to predict detrusor urodynamics. Urodynamic diagnosis was based on the detrusor pressure-flow study. We observed ultrastructural degenerative cell changes with statistical significance in impaired detrusor contractility such as no branching and intertwining of cells, absence of caveoles, perinuclear degeneration with vacuolization, destructured myofilament system with diminished anchorage plates and collagen infiltrating the interstitium with loss of bladder muscle fascicle organization. CONCLUSIONS: Impaired detrusor contractility is a urodynamic diagnosis that should be taken into account in patients with prostatism. The diagnosis of this condition requires performing a pressure-flow study. Impaired detrusor contractility showed a morphological and ultrastructural correlation with degenerative changes of the bladder muscle.     

Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation

PURPOSE: We test the hypothesis that women without chronic pelvic pain or irritative voiding symptoms do not demonstrate petechial hemorrhages known as glomerulations that are characteristic of patients with interstitial cystitis. MATERIALS AND METHODS: A prospective cohort design was used for examination with cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal ligation. Cystoscopy with the patient under general anesthesia was performed to inspect the bladder mucosa before and after distention at 70 cm. of water pressure for 2 or 6 minutes. Photographs of the right, posterior and left of the bladder surfaces taken before and after the distention were scored on a scale of 1 to 5 using a panel of standards. Five urologists blinded to the source of individual photographs independently evaluated 120 research images interspersed with 46 other pictures from a library containing images from 19 symptomatic patients with and without interstitial cystitis. RESULTS: A total of 20 normal women with a mean age plus or minus standard deviation of 29+/-6 years consented to participate in this trial during laparoscopic tubal ligation. Photographs of bladder sites before and after distention with 890+/-140 ml. were scored as 1.4+/-0.3 (before distention) and 3.1+/-1.1 (after distention) on the scale of 1 to 5. The increase in scores following distention in normal subjects was seen to the same degree and in the same proportion as in patients with symptoms of interstitial cystitis (8 of 19 symptomatic patients in this series met current diagnostic criteria for interstitial cystitis). Slight but significant differences were seen among sites in the bladder but not between 2 and 6-minute distention durations. CONCLUSIONS: Bladder mucosal lesions characteristically associated with irritative voiding symptoms and pelvic pain in patients diagnosed with interstitial cystitis were observed in asymptomatic women.     

Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study. Calcipotriol Study Group

PURPOSE: Ultrasound estimated bladder weight was compared before and after surgery for benign prostatic hyperplasia (BPH) to reveal a possible reversible change in bladder hypertrophy. MATERIALS AND METHODS: Ultrasound estimated bladder weight was measured before and after subcapsular (17) or transurethral (16) prostatectomy in 33 male patients with BPH. Sequential changes in the American Urological Association symptom score and urinary flow rate were also examined. RESULTS: Along with a significant improvement in the American Urological Association symptom scores and maximum flow rate, ultrasound estimated bladder weight decreased from 52.9 +/- 22.6 to 31.6 +/- 15.8 gm. in 12 weeks after treatment. In all but 4 patients (29 of 33, or 87.9%) ultrasound estimated bladder weight decreased to less than 35.0 gm. in 12 weeks after treatment. Interestingly, in all patients with an initial ultrasound estimated bladder weight of greater than 80 gm. the bladder weight still remained at an abnormally high level 12 weeks after treatment. CONCLUSIONS: Bladder hypertrophy was completely reversible after the surgical treatment of the obstruction in the majority of patients with BPH. The measurement of ultrasound estimated bladder weight was of value in monitoring therapeutic effects in BPH patients. An extraordinarily high ultrasound estimated bladder weight of 80 gm. or more might suggest degenerative and irreversible pathological changes in the bladder detrusor.     

Quantitative studies of the kinetics of 5-aminolaevulinic acid-induced fluorescence in bladder transitional cell carcinoma

Photodynamic therapy is a potential treatment for superficial bladder cancer that utilizes photosensitizer drugs, which are activated by light to cause tissue destruction. However, first-generation photosensitizers cause prolonged phototoxicity, have poor tumour specificity and can accumulate within detrusor muscle, resulting in permanent loss of bladder capacity following treatment. A newer drug, called 5-aminolaevulinic acid (ALA), generates a sensitizer called protoporphyrin IX (PpIX) in situ and has been shown, qualitatively, to be more tumour specific. The fluorescence kinetics of ALA-induced PpIX was investigated in patient biopsies of bladder tumour, normal urothelium and detrusor muscle, both in vitro after incubation of specimens in ALA-rich culture medium for various times and in vivo after instillation of intravesical ALA before endoscopic resection. The fluorescence in tumour tissue was twice that of normal urothelium in vitro and up to tenfold in vivo. There was little ALA-induced fluorescence in detrusor muscle, both in vitro and in vivo. Most importantly, no patients experienced phototoxicity or other adverse events following intravesical instillation of ALA.     

Transient hypothermia induces micronuclei in mice

Individuals with spinal cord injury and multiple sclerosis are at high risk for developing kidney dysfunction due to high bladder pressures. We have developed a device for frequent monitoring of bladder pressures at home in those patients who use intermittent catheterization to empty their bladders. Of eight subjects enrolled in the study, only five conducted home recording of pressure. Vesical and abdominal pressures measured at home were significantly lower than clinical cystometric pressures. However, subtracted detrusor pressures obtained from home records and cystometric records were not significantly different. The home detrusor pressures were consistent over a large time and volume range. Therefore, the home monitoring method could be used to establish a normal range of bladder pressures at home and to rapidly identify high bladder pressures in advance of upper urinary tract deterioration.     

Effect of neonatal surfactant therapy on lung function at school age in children born very preterm

BACKGROUND: Involuntary detrusor contractions often cause irritative symptoms such as urgency and incontinence. A dog model for acutely induced variable bladder outlet resistance was developed to investigate the possible role of prostatic afferent nerve fibers in the development and maintenance of detrusor instability. METHODS: Fifty-eight mongrel dogs (weight range 19.5-36.5 kg) were divided into five groups: group I (n = 11) had surgically induced bladder outlet obstruction. Group II (n = 14) had urinary obstruction and bilateral sectioning of the lowest branches of the pelvic plexus supplying the prostate. Group III (n = 10) had prostate denervation only. Groups IV (n = 10) and V (n = 13) were sham-operated and controls, respectively. In the obstructed groups (I and II), an artificial urinary sphincter (length 4.5-6.0 cm) was placed around the bladder neck and connected to a reservoir placed subcutaneously to allow postoperative adjustments of urinary resistance. All dogs were evaluated at baseline and postoperatively at 1, 3, and 6 months with uroflowmetry, postvoid residual urine volume, cystometry as well as serum creatinine, and urinalysis. RESULTS: Occurrences of detrusor instability were not associated with prostatic denervation input. The mean peak flow rates decreased significantly in the obstructed groups at all follow-ups, but did not change significantly in the nonobstructed groups. Postoperatively, the mean maximum bladder capacity was significantly decreased for groups I and II only. However, a significant correlation between maximum bladder capacity and maximum detrusor pressure could not be detected at any time point in any of the groups. Mean postvoid residual urine volume varied considerably in all groups over time. Creation of a urinary model of infravesical obstruction was associated with considerable problems. CONCLUSIONS: In our dog model of bladder outlet obstruction, prostatic sensory nerve fibers appear not to be involved in detrusor instability. Surgical induction of a constant model of bladder outlet obstruction was difficult even in a large animal. The observations from the present study raise questions about the validity of obstructive urinary animal models.