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S V Yalla

Publications and source records attributed to S V Yalla.

At least 19 recordsLinked to original sources
PubMed2007

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions.

AIMS: Caveolae are cholesterol-rich plasmalemmal microdomains that serve as sites for sequestration of signaling proteins and thus may facilitate, organize, and integrate responses to extracellular stimuli. While previous studies in the bladder have demonstrated alterations in caveolae with particular physiologic or pathologic conditions, little attention has been focused on the functional significance of these organelles. Therefore, the purpose of this study was to investigate the role of caveolae in the modulation of receptor-mediated signal transduction and determine the presence and localization of caveolin proteins in bladder tissue. METHODS: Contractile responses to physiologic agonists were measured in rat bladder tissue before and after disruption of caveolae achieved by depleting membrane cholesterol with methyl-beta-cyclodextrin. Stimulation with agonists was repeated after caveolae were restored as a result of cholesterol replenishment. RT-PCR, immmunohistochemistry, and Western blotting were used to determine the expression and localization of caveolin mRNA and proteins. RESULTS: Following caveolae disruption, contractile responses to angiotensin II and serotonin were attenuated, whereas responses to bradykinin and phenylephrine were augmented. Cholesterol replenishment restored responses towards baseline. Carbachol and KCl induced contractions were not affected by caveolae disruption. Ultrastructure analysis confirmed loss of caveolae following cholesterol depletion with cyclodextrin and caveolae restoration following cholesterol replacement. Gene and protein expression of caveolin-1, -2, and -3 was detected in bladder tissue. Immunoreactivity for all three caveolins was observed in smooth muscle cells throughout the bladder. CONCLUSIONS: The functional effects of cholesterol depletion on specific agonist-induced contractile events and the expression of all three caveolins in bladder smooth muscle support a central role for caveolae in regulation of selective G-protein-coupled receptor signaling pathways in bladder smooth muscle. Thus, caveolae serve to differentially regulate bladder smooth muscle by a stimulus-dependent potentiation or inhibition of bladder contraction.

Angiotensin II↗
PubMed2000

Penile urethral compression-release maneuver as a non-invasive screening test for diagnosing prostatic obstruction.

The purpose of this study was to evaluate the feasibility of using a penile urethral compression and quick release maneuver during urination as a potential non-invasive clinical screening tool in the evaluation of patients with voiding dysfunction and the diagnosis of prostatic obstruction. The penile compression-release maneuver was performed in adult men with symptomatic voiding dysfunction and in asymptomatic normal men by compressing the penile urethra for 2-3 seconds after the initiation of flow and quickly releasing the compression. The penile compression-release index, calculated from the resulting flow rate surge (Q(surge)) and the steady flow rate (Q(surg)-Q(s)/Q(s)), was analyzed with respect to the type of voiding dysfunction. A comprehensive urodynamic study was performed in each patient to determine the presence and severity of prostatic obstruction and to measure detrusor contractility. The penile compression-release indices measured with this maneuver in patients with bladder outlet obstruction (183+/-76%, n = 43) or detrusor instability (157+/-65%, n = 13) were significantly greater than the index observed in non-obstructed patients with normal contractility (67+/-37%, n = 24) or in non-obstructed patients with impaired detrusor contractility (70+/- 32%, n = 10). In asymptomatic younger men who had normal free flow rates (>15 mL/s), the penile compression-release index (55+/-29%, n = 20) was significantly less than that observed in patients with outlet obstruction or detrusor instability. These findings suggest that the magnitude of the flow rate change generated after the penile compression-release maneuver depends on the magnitude of the isometric detrusor contraction developed during penile urethral compression and on the conduit status of the outlet. In patients determined to have poor urinary flow rates, this non-invasive maneuver has been able to differentiate prostatic obstruction associated with normal detrusor contractility from other causes of low urinary flow rates. Despite these encouraging trends, further studies in a larger cohort are required to determine its potential clinical utility as a screening tool for diagnosing prostatic obstruction.

Adult↗
PubMed2000

Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction.

PURPOSE: Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. MATERIALS AND METHODS: Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. RESULTS: Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. CONCLUSIONS: The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.

Animals↗
PubMed2000

Effect of radical prostatectomy on sensory threshold and pressure transmission.

PURPOSE: The mechanisms involved in post-radical prostatectomy incontinence remain unclear despite previous anatomical and functional studies. In addition, the factors responsible for the restoration of continence are not well studied. To improve our understanding of the alterations in continence mechanisms, we prospectively investigated the temporal changes in urodynamic parameters after radical prostatectomy. MATERIALS AND METHODS: Cystometry, urethral pressure profilometry and posterior urethral sensory threshold measurements were performed in patients undergoing radical prostatectomy. Preoperative pressure transmission was determined by the maximal urethral pressure divided by the maximal abdominal pressure during cough maneuvers at a bladder volume of 200 ml. Postoperative sensory threshold, pressure transmission (% of pressure transmission), maximal urethral closure pressure and functional sphincter length were measured 6 weeks and 6 months after prostatectomy. These parameters were compared between continent and incontinent patients. RESULTS: Preoperative and postoperative urodynamic studies were completed in 34 patients. The continence rate after 6 weeks was 18% (6 patients) and improved to 82% (28) after 6 months. Preoperatively sensory threshold was 16 +/- 11 mA. After 6 weeks and 6 months, respectively, sensory threshold was significantly higher in incontinent (84 +/- 11 mA., 70 +/- 8 mA.) compared to continent (65 +/- 8 mA., 41 +/- 12 mA.) patients. Preoperative proximal urethral sensory threshold was not correlated with degree of postoperative incontinence determined by pad tests. Pressure transmission was not different in continent and incontinent patients postoperatively. After 6 weeks and 6 months, respectively, pressure transmission was 77% and 91% in continent, and 37% and 58% in incontinent patients (p = 0.04, p = 0.03). Maximal urethral closure pressure was significantly higher in continent patients (35 +/- 6 cm. H2O) compared to incontinent patients (11 +/- 9 cm. H2O). Sphincter length decreased from 50 mm. preoperatively to 24 mm. after 6 weeks and 25 mm. after 6 months. There was no difference in sphincter length between continent and incontinent patients. CONCLUSIONS: Posterior urethral sensitivity and pressure transmission are impaired immediately after prostatectomy. An improvement in these parameters after 6 months is associated with the restoration of continence. These observations suggest that urinary continence after radical prostatectomy depends on the integrity of posterior urethral sensation and the efficiency of pressure transmission.

Humans↗
PubMed2000

Combination of symptom score, flow rate and prostate volume for predicting bladder outflow obstruction in men with lower urinary tract symptoms.

PURPOSE: The severity of lower urinary tract symptoms associated with benign prostatic enlargement correlates poorly with bladder outlet obstruction. Since urodynamic studies are presumed to be relatively complex, invasive and not cost-effective, they are not routinely performed by physicians treating men with lower urinary tract symptoms. As a result, a large number of patients are treated for bladder outlet obstruction when in fact obstruction may not be present. Since other noninvasive methods have not been effective for predicting bladder outlet obstruction, we investigated whether a combination of prostate volume, uroflowmetry and the American Urological Association (AUA) symptom index would be reliable for predicting this condition. MATERIALS AND METHODS: We prospectively evaluated 204 men with a mean age plus or minus standard deviation of 66.7 +/- 7.5 years who presented with lower urinary tract symptoms. Each patient completed an AUA symptom index questionnaire and underwent uroflowmetry, post-void residual urine volume measurement, pressure flow study and transrectal ultrasound of the prostate to estimate prostatic volume. We constructed receiver operating characteristics curves using various threshold values for maximum urine flow and prostate volume. Threshold values for maximum urine flow and prostate volume were used alone and combined with the AUA symptom index for predicting bladder outlet obstruction. We selected a cutoff value for maximum urine flow of 10 or less ml. per second and prostate volume of 40 gm. or greater, and used these values with an AUA symptom index of greater than 20 to predict bladder outlet obstruction in the group overall. RESULTS: Differences in the mean symptom index score in men with and without bladder outlet obstruction were not statistically significant. There was no obstruction in 19%, 28.9% and 35% of those with severe, moderate and mild symptoms, respectively. The selected cutoff values of maximum urine flow, prostate volume and symptom score combined correctly predicted obstruction in all 39 patients. Therefore, our combination of cutoff values proved to be highly accurate for predicting bladder outlet obstruction. Sensitivity, specificity, and positive and negative predictive values were 26%, 100%, 100% and 32%, respectively. CONCLUSIONS: Our study showed that combining the AUA symptom index, maximum urine flow and prostate volume reliably predicted bladder outlet obstruction in a small subset of patients only. Although bladder outlet obstruction was correctly predicted by our threshold values of AUA symptom index, maximum urine flow and prostate volume in only 39 men (26%) with obstruction, these patients represent a substantial group in any large urological practice treating male lower urinary tract symptoms.

Aged↗
PubMed1999

The flow regimes and the pressure-flow relationship in the canine urethra.

Classical fluid dynamics predicts that the pressure difference Deltap between any two points along a fully developed, viscous flow stream is linearly proportional to the flow rate Q (the Poiseuille relation). However, the passive urethral resistance relationship (PURR) widely used in modern urodynamics describes the pressure difference Deltap between two points along the urethra as linearly proportional to the flow rate squared (Q(2)). It is our hypothesis that this functional dependence may have its origins in the developing flow field within the urethra. That is, rather than being fully developed hydrodynamically, urethral flow is more likely representative of flow within the entry length of a rigid conduit. In our study, we used a canine model of the lower urinary tract to investigate the possibility of entrance effects. Although the most rigorous model of urethral fluid mechanics would include the elastic properties of the urethra into its configuration, the solutions from such a model would be unnecessarily complex and not readily lend themselves to the analysis of clinical data. Therefore, we chose to model the canine urethra at each instant in time as a rigid tube, and characterized its instantaneous flow using viscous flow theory for a rigid tube. All urodynamic analyses were performed on a surgically exposed urinary tract. Solid state pressure transducers were used to measure the intravesical and distal urethral pressures, whereas an ultrasonic flowmeter was used to obtain a simultaneous measure of the urinary flow rate. Detrusor contractions were induced using bilateral electrical stimulation of the pelvic nerves. Varying degrees of outlet obstruction were created using an inflatable sphincter cuff secured around the bladder outlet. The experimental data were evaluated using the well-known laminar entry length model of Atkinson and Goldstein. The peak Reynolds numbers under nonobstructed R(p)(e non-obs) and obstructed R(p)(e obs) outlet conditions ranged between 500 < R(p)(e non-obs) < 1,500 and 300 < R(p)(e obs) < 1,700, respectively. Under non-obstructed outlet conditions, the urethral diameters D and total lengths l(T) ranged between 1.5 mm < D < 2.5 mm and 75 mm < l(T) < 95 mm, respectively, whereas the peak entrance lengths L(p)(e non-obs) ranged between 55 mm < L(p)(e non-obs) < 215 mm. These data suggest that flow in the canine urethra under both non-obstructed and obstructed outlet conditions is typically laminar. The data further support the hypothesis that non-obstructed flows are predominantly entry length in nature. Entry length flows are fluid dynamically described by a quadratic pressure-flow relationship, thus suggesting a physiological basis for Schäfer's quadratic pressure-flow relationship, and therefore, for the PURR. Neurourol. Urodynam. 18:521-541, 1999.

Animals↗
PubMed1999

Urodynamic characterization of nonobstructive voiding dysfunction in symptomatic elderly men.

PURPOSE: The pathogenesis of lower urinary tract symptoms in men without bladder outlet obstruction has not been well characterized. Therefore, we defined the urodynamic abnormalities associated with symptomatic nonobstructive voiding dysfunction, and determined the relationship between age and type of dysfunction. MATERIALS AND METHODS: Video urodynamic studies of symptomatic men without outlet obstruction were examined. The criterion for a normal bladder outlet was a pressure gradient across the prostatic urethra of 5 cm. water or less in the absence of distal stricture. A maximum isometric contraction pressure less than 60 cm. water was regarded as impaired detrusor contractility. Detrusor instability was defined as involuntary detrusor contractions during filling or the inability to suppress a detrusor contraction after initiation of flow. Patients were categorized into 4 groups based on the urodynamic findings. RESULTS: Of 193 men (mean age 69.6+/-10.5 years) 40.9% had detrusor instability (group 1), 31.1% had impaired contractility (group 2), 10.8% had detrusor instability and impaired contractility (group 3), and 17.1% were urodynamically normal (group 4). Average patient age was significantly lower in group 4 than all other groups. Bladder capacity was lowest in group 1, and group 3 had the lowest voiding efficiency. Maximum flow rate, bladder compliance and symptom scores were not different among the 4 groups. The prevalence of detrusor instability with and without impaired contractility increased, while the proportion of patients without urodynamic abnormalities decreased with age. Bladder contractility did not correlate with age. CONCLUSIONS: The nonobstructed patient population comprises several groups that are functionally distinct while symptomatically similar. Thus, treatment of nonobstructed cases based on symptoms may lead to inappropriate pharmacological therapy and unsuccessful clinical outcomes.

Adult↗
PubMed1998

The maximum watts factor as a measure of detrusor contractility independent of outlet resistance.

The maximum watts factor (WFmax) is often used to characterize detrusor contractility. It was recently shown that the WFmax may increase in some patients with chronic outlet obstruction. It is, however, unclear whether this increase reflects a dependence of the WFmax on the degree of outlet obstruction or whether it represents a true increase in detrusor contractility secondary to chronic outlet obstruction. Therefore, this study was performed to investigate this issue using a canine model of acute outlet obstruction. Urodynamic studies were performed on adult canines with surgically exposed lower urinary tracts. Pressure transducers were used to measure the intravesical and the distal urethral pressures, whereas an ultrasonic flow meter was used to obtain a simultaneous measure of the urinary flow rate. Detrusor contractions were induced by electrically stimulating the pelvic nerves bilaterally. Varying degrees of outlet obstruction were created using an inflatable sphincter cuff secured around the bladder outlet. The WFmax, the detrusor pressure at voiding terminus (Pdet.clos), and the passive urethral resistance (R) were computed from measured pressure-flow rate data at each degree of outlet obstruction. The WFmax was not significantly correlated to either the sphincter cuff volume (r = 0.025, p = 0.871), the Pdet.clos (r = 0.286, p = 0.073) or the R (r = 0.110, p = 0.509). The WFmax was not significantly different among mild, moderate, and severe degrees of outlet obstruction (p = 0.176). Our results suggest that the WFmax is independent of the degree of acute outlet obstruction (defined in terms of the sphincter cuff volume, Pdet.clos and R). This validates the current practice of using the WFmax to evaluate detrusor function in patients with voiding dysfunction regardless of outlet resistance. Further, since the WFmax is independent of outlet obstruction acutely, it is reasonable that it would also be independent of outlet obstruction under chronic conditions. Our results, therefore, also imply that the increase in the WFmax with chronic outlet obstruction may represent a true increase in detrusor contractility and not a WFmax dependence on outlet resistance.

Animals↗
PubMed1998

Improving the utility of urine flow rate to exclude outlet obstruction in men with voiding symptoms.

OBJECTIVES: Many older men with voiding symptoms do not have bladder outlet obstruction (BOO) but have conditions amenable to medical treatment. If primary care providers could reliably exclude men who have BOO, then they could initiate appropriate evaluation and treatment in a substantial proportion of the remainder. Urine flow rate, although widely used, is insufficiently sensitive to exclude BOO reliably. We investigated whether the decline in flow rate with age could be utilized to improve the utility of flow rate for excluding BOO in symptomatic men, especially when combined with knowledge of the patient's postvoiding residual volume (PVR). DESIGN: Prospective study using two patient cohorts. SETTINGS: A Veterans Affairs urology clinic serving community-dwelling and institutionalized healthy older men. PARTICIPANTS: 111 men with voiding symptoms (mean age 72.4 +/- 9.2 years). MEASUREMENTS: Maximum urine flow rate, measured with standard flowmeter, and PVR, measured by catheterization. BOO was determined by multichannel videourodynamic testing. RESULTS: The sensitivity of flowrate for BOO increased significantly with age (P = .0001) and did not appear to be confounded by comorbid conditions. An algorithm incorporating age, flow rate, and PVR had a sensitivity of 90%, specificity of 43%, and accuracy of 74% in screening for BOO. The algorithm's sensitivity was better than that of flow rate alone (55%); its sensitivity was also similar to a "refer all" strategy (100%) but had improved specificity (41% vs 0%). CONCLUSIONS: Flow rate alone is insufficiently sensitive as a screening test to exclude BOO, but a simple diagnostic algorithm using age, flowrate, and PVR was more sensitive and accurate. This algorithm allows primary care evaluation and initial management of men with voiding symptoms while potentially reducing unnecessary referrals and costs.

Aged↗
PubMed1998

Detrusor contraction duration as a urodynamic parameter of bladder outlet obstruction for evaluating men with lower urinary tract symptoms.

PURPOSE: Recent studies suggest that detrusor contraction duration increases with bladder outlet obstruction and correlates with the American Urological Association (AUA) symptom index. Since the detrusor contraction duration may also depend on detrusor contractility and bladder volume, its use alone in characterizing bladder outlet obstruction is debatable. Therefore, we studied the relationship between detrusor contraction duration and bladder outlet obstruction, bladder capacity, detrusor contractility and symptoms to determine whether detrusor contraction duration is a useful parameter for characterizing bladder outlet obstruction in men with lower urinary tract symptoms. MATERIALS AND METHODS: Pressure-flow studies were performed in men with lower urinary tract symptoms. Bladder outlet obstruction was defined as passive urethral resistance relation greater than grade II and contractility was determined from Schäfer's nomogram. Detrusor contraction duration was defined as the contraction time elapsed between the first rise in detrusor pressure from baseline to the time at which detrusor pressure returned to baseline at the end of voiding. AUA symptom index was attained from each patient and categorized as mild (0 to 7), moderate (8 to 19) and severe (20 to 35). RESULTS: Detrusor contraction duration was determined from 58 consecutive pressure-flow studies. This parameter was not significantly different among 23 patients with mild (116.7+/-34.0 seconds), 15 with moderate (102.7+/-61.9 seconds) and 9 with severe (89.2+/-44.4 seconds) AUA symptom index scores. AUA symptom index, as well as irritative and obstructive scores did not significantly correlate with detrusor contraction duration. Detrusor pressure at maximal flow was weakly correlated with detrusor contraction duration (r=0.322, p=0.014). However, detrusor contraction duration in 27 obstructed patients (111.6+/-53.7 seconds) was not significantly different from that of 31 nonobstructed patients (91.5+/-41.5 seconds) and it did not increase with the severity of bladder outlet obstruction. Detrusor contraction duration in 40 patients with good contractility (94.3+/-49.2 seconds) was significantly lower than in 18 patients with poor contractility (115.5+/-43.3 seconds). Detrusor contraction duration was significantly lower in nonobstructed patients with good contractility (72.0+/-21.7 seconds) compared with either nonobstructed patients with poor contractility (118.4+/-47.7 seconds) or obstructed patients with good contractility (112.5+/-58.0 seconds). There was no difference in detrusor contraction duration between nonobstructed patients with poor contractility and obstructed patients with good contractility. Multiple regression analysis showed that detrusor contraction duration can be best predicted by a combination of detrusor pressure at maximal flow, bladder capacity and contractility (r=0.576). CONCLUSIONS: Our study showed that detrusor contraction duration cannot distinguish patients with from those without bladder outlet obstruction, and it does not correlate with the severity of symptoms. Since our results also showed that detrusor contraction duration depends on several factors related to detrusor and outlet function, it cannot be used as a reliable parameter to diagnose bladder outlet obstruction.

Aged↗
PubMed1997

Initiation of voiding in humans: the nature and temporal relationship of urethral sphincter responses.

PURPOSE: The nature and sequence of events during the initiation phase of human micturition are unclear. Disagreement concerning the urethral sphincter response to detrusor contraction may stem from the functional extension of periurethral striated muscle to the bladder neck in many but not all individuals, and the methods used during conventional cystometry, in which individuals are asked to forestall urination for as long as possible (urgency voiding). We reasoned that by instructing individuals to void despite the lack of urgency (volitional voiding), and by stratifying results by whether striated muscle influence extended to the bladder neck, response of the proximal urethra might be more readily determined. MATERIALS AND METHODS: Using a triple microtip transducer catheter and a triple lumen fluid-filled catheter, we investigated 44 consecutive men and women with a variety of urodynamic findings, including 12 whose evaluation was normal. RESULTS: Despite the diversity of urodynamic diagnoses, once data were stratified as described, results were striking and uniform. The smooth muscle component of the bladder neck region contracted during the initiation of voiding in all subjects. Despite antecedent relaxation of the striated muscle sphincter, voiding did not begin until bladder pressure equaled or exceeded bladder neck pressure. CONCLUSIONS: Proximal urethral pressure increases in the initial phase of human micturition. These findings may have significant physiological, diagnostic and therapeutic implications.

Adult↗
PubMed1997

Retrograde leak point pressure for evaluating postradical prostatectomy incontinence.

OBJECTIVES: To evaluate a technique of measuring the retrograde leak point pressure (RLPP) for assessing men with postradical prostatectomy stress urinary incontinence (SUI). METHODS: We measured RLPP in adult men by retrograde infusion of the distal urethra while simultaneously recording intraurethral pressure. The reproducibility of this test, and its dependence on urethral infusion rate, bladder volume, and anterior urethral catheter position, were evaluated. RLPP and abdominal leak point pressure (ALPP) measurements were performed in postradical prostatectomy patients. RLPP was compared with ALPP and with severity of incontinence determined by pad usage. RESULTS: Repeated RLPP measurements were not significantly different and did not change with bladder volume up to half capacity or with the location of the catheter in the anterior urethra. The differences between RLPP measurements with infusion rates of 2, 4, and 8 mL/min were also not significant. Twenty-seven men were evaluated 6 to 108 months after surgery. Of these, 22 (81%) demonstrated SUI. Mean RLPP in men without SUI (79.2 +/- 14 cm H2O) was significantly higher than in men with SUI (51.9 +/- 13 cm H2O, P < 0.01). In men with SUI, ALPP and RLPP were significantly correlated, and ALPP (49.8 +/- 24 cm H2O) was not significantly different from RLPP (51.9 +/- 13 cm H2O) Pad use and RLPP were also significantly related. CONCLUSIONS: RLPP measurements are reproducible and simple to perform. The pressure at which leakage occurs is easily identifiable as the plateau pressure. RLPP correlates significantly with the lowest of multiple ALPP measurements in men with SUI. This technique represents a reliable urodynamic alternative for evaluating men with postradical prostatectomy SUI.

Aged↗