Uropathic observations in mice expressing a constitutively active point mutation in the 5-HT3A receptor subunit. (25/154)

Mutant mice with a hypersensitive serotonin (5-HT)3A receptor were generated through targeted exon replacement. A valine to serine mutation (V13'S) in the channel-lining M2 domain of the 5-HT3A receptor subunit rendered the 5-HT3 receptor 70-fold more sensitive to serotonin and produced constitutive activity when combined with the 5-HT3B subunit. Mice homozygous for the mutant allele (5-HT3Avs/vs) had decreased levels of 5-HT3A mRNA. Measurements on sympathetic ganglion cells in these mice showed that whole-cell serotonin responses were reduced, and that the remaining 5-HT3 receptors were hypersensitive. Male 5-HT3Avs/vs mice died at 2-3 months of age, and heterozygous (5-HT3Avs/+) males and homozygous mutant females died at 4-6 months of age from an obstructive uropathy. Both male and female 5-HT3A mutant mice had urinary bladder mucosal and smooth muscle hyperplasia and hypertrophy, whereas male mutant mice had additional prostatic smooth muscle and urethral hyperplasia. 5-HT3A mutant mice had marked voiding dysfunction characterized by a loss of micturition contractions with overflow incontinence. Detrusor strips from 5-HT3Avs/vs mice failed to contract to neurogenic stimulation, despite overall normal responses to a cholinergic agonist, suggestive of altered neuronal signaling in mutant mouse bladders. Consistent with this hypothesis, decreased nerve fiber immunoreactivity was observed in the urinary bladders of 5-HT3Avs/vs compared with 5-HT3A wild-type (5-HT3A+/+) mice. These data suggest that persistent activation of the hypersensitive and constitutively active 5-HT3A receptor in vivo may lead to excitotoxic neuronal cell death and functional changes in the urinary bladder, resulting in bladder hyperdistension, urinary retention, and overflow incontinence.  (+info)

Urinary bladder contraction and relaxation: physiology and pathophysiology. (26/154)

The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.  (+info)

Doxazosin effects on cholinergic and adrenergic responses in rat isolated detrusor smooth muscle preparations from obstructed bladder. (27/154)

We investigated the effect of doxazosin on cholinergic and adrenergic agonists responses in detrusor smooth muscle preparations from sham-operated and 2-week partially obstructed rat bladders. Male Wistar albino rats, 200-250 g, were randomly allocated to 4 experimental groups consisting of 12 animals each: sham-operated bladder, sham-operated bladder treated with doxazosin, partially obstructed bladder, and partially obstructed bladder treated with doxazosin. Partial outlet obstruction of the rat was surgically induced. The response to carbachol (10(-7)-10(-4) M), isoproterenol (10(-6)-10(-3) M), and 80 mM KCl were recorded. Carbachol caused concentration-dependent contractile responses in the detrusor smooth muscles from sham-operated and partially obstructed bladder. Isoproterenol produced concentration-dependent relaxation responses in the detrusor strips from all groups. Dose-response curves for carbachol and isoproterenol showed a shift to the left in rat detrusor smooth muscles from partially obstructed bladder when compared with the results obtained in detrusor muscles from sham-operated bladder. These responses were reversed to normal by doxazosin treatment in rat detrusor smooth muscles from partially obstructed bladder. KCl produced contractile responses in rat detrusor smooth muscles from all groups. The contractile responses to KCl were not significantly changed in all groups. We have shown that carbachol and isoproterenol responses were shifted to the left in rat detrusor smooth muscles from partially obstructed bladder and these responses were reversed by doxazosin treatment.  (+info)

International Prostate Symptom Score--IPSS-AUA as discriminat scale in 400 male patients with lower urinary tract symptoms (LUTS). (28/154)

OBJECTIVE: This study analyzed the total symptom score, irritative and obstructive domains of IPSS questions regarding quality of life and the urodynamic diagnosis in 400 men with LUTS. MATERIALS AND METHODS: Four hundred consecutive male patients were prospectively enrolled after being submitted to full urodynamic evaluation and IPSS. Obstructed and non-obstructed patients were compared regarding the symptoms score and quality of life. Results were assessed through Wilcox, ANOVA and Student-t tests. RESULTS: 80.2% were diagnosed as urodynamically obstructed of which 42.4% presented detrusor instability in the filling phase. In obstructed patients there were no statistical difference concerning obstructive or irritative questions from IPSS (p = 0.50). It was not possible either to predict which patients presented detrusor instability based on the questionnaire (p = 0.65). Out of seventy-nine cases unobstructed (19.8%), 65.4% revealed detrusor instability. These cases could not be distinguished from all obstructed men based on the clinical questions measured by IPSS (p = 0.87). Obstructive and irritative questions did not present different indexes than obstructed cases (p = 0.63). Subjective quality of life index did not discriminate obstruction nor it could predict detrusor instability in both groups. CONCLUSION: Clinical symptoms and quality of life index measured by the IPSS as well as its obstructive and irritative domains do not have discriminating power to predict the presence of infravesical obstruction in males with LUTS, demanding objective tools to demonstrate obstruction.  (+info)

Symptomatic local recurrence of prostate carcinoma after radiation therapy. (29/154)

BACKGROUND: Symptomatic local recurrence of prostate carcinoma (SLRPC) after radiation therapy (RT) is associated with morbidity and debilitating symptoms that have a substantial impact on the patient's quality of life. Most reports on the results of RT for localized prostate carcinoma (PC) do not address this endpoint. The objective of this study was to determine the incidence of SLRPC and to identify the risk factors for this endpoint. METHODS: The medical charts of 1006 patients who received RT for localized PC at the University of Texas M. D. Anderson Cancer Center between 1987 and 1997 were reviewed. Local symptoms were defined as hematuria, voiding symptoms, urinary obstruction, and pelvic pain. Progressive symptoms accompanied by either confirmatory histology or cystoscopic findings were attributed to PC. Univariate and multivariate analyses using Cox proportional hazards models were applied to identify risk predictors. RESULTS: Among 964 patients for whom follow-up data were available, 277 patients had prostate-specific antigen (PSA) progression, and 45 patients died of PC during a median follow-up of 9.4 years. In total, 33 patients (3.4%) developed SLRPC. In patients who experienced biochemical progression, the actuarial 5-year incidence of SLRPC was 8.3%. Among the patients who had developed SLRPC, 23 patients (69.7%) died of PC at a median of 25.3 months from the onset of local symptoms. Adverse histologic tumor subtypes (ductal, small cell, and sarcomatoid) were associated significantly with SLRPC (hazard ratio, 8.4; 95% confidence interval, 2.99-23.63). Clinical T classification at diagnosis, Gleason score, and initial PSA level showed a trend toward an increased hazard ratio. CONCLUSIONS: SLRPC after radiotherapy therapy was an uncommon but clinically significant event. Aggressive histologic subtypes were predictive of this endpoint. Clinical T classification, Gleason score, and initial prostate-specific antigen levels also may have predictive value.  (+info)

Bladder outlet obstruction in a 6-month-old alpaca secondary to pelvic displacement of the urinary bladder. (30/154)

A 6-month-old female alpaca was presented for stranguria. Based on the history, physical examination findings, and radiographic studies, the alpaca was diagnosed with bladder outlet obstruction, secondary to pelvic displacement of the bladder, a condition previously unreported in camelids. Cystopexy was performed and the alpaca recovered unremarkably.  (+info)

Moderately T2-weighted images obtained with the single-shot fast spin-echo technique: differentiating between malignant and benign urinary obstructions. (31/154)

The purpose of this study was to determine whether a distinction could be made between benign and malignant urinary obstructions in moderately T(2)-weighted images obtained with the single-shot fast spin-echo technique. Forty-four lesions in 39 patients with urinary obstruction were evaluated with the single-shot fast spin-echo (SSFSE) technique with an effective TE of 90-100 ms and without fat saturation. Benign and malignant lesions were compared for the presence of ureteral wall thickening and a signal intensity relative to the proximal ureteral wall. Statistically significant differences were found between benign and malignant lesions in both morphologic change (P<0.0001) and signal intensity of the lesions at the obstruction position (P<0.0001). The combination of wall thickening and increased signal intensity as a predictor of malignant disease yielded a sensitivity of 88% and a specificity of 100%. Neither increased signal intensity nor wall thickening as a predictor of benign disease yielded a sensitivity of 89% and a specificity of 88%. The moderately T(2)-weighted SSFSE technique without fat saturation can accurately distinguish between benign and malignant urinary obstructions.  (+info)

L-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction. (32/154)

Partial bladder outlet obstruction (PBOO) results in cellular damage due to ischemia and reperfusion injury. Our study seeks to establish how early this damage can occur and the role that nitric oxide may play in its pathophysiology. Surgical PBOO (1, 3, and 7 days) were performed on male New Zealand White rabbits. Half of the animals were premedicated for 3 days with N(G)-nitro-l-arginine methyl ester(l-NAME), an inhibitor of nitric oxide synthase before obstruction. Bladder weight increased with duration of PBOO but was significantly lower at 3 and 7 days in animals treated with l-NAME compared with their untreated counterparts. Contractile function decreased progressively with PBOO duration. At 1 day postobstruction, bladder contractility was significantly lower in the l-NAME rabbits than in the untreated rabbits. At 3 and 7 days, contractility of the l-NAME bladders was equal or higher than the untreated bladders. The level of hypoxia at 1 day after obstruction was significantly higher in the l-NAME-treated animals than in the untreated controls but equal at 3 and 7 days obstruction. Increased nitrotyrosine was seen by Western blot in all obstructed animals. However, the amount was significantly less in the l-NAME-treated animals at 3 and especially at 7 days. Nerve density decreased progressively after obstruction; however, it decreased to a significantly lesser degree in the l-NAME-treated bladders than in the untreated groups. These results suggest that l-NAME pretreatment enhanced ischemic damage at 1 day after obstruction but protected the bladder from nitric oxide-generated free radical damage at the later time periods by inhibiting the generation of nitrotyrosine.  (+info)