-
[show abstract]
[hide abstract]
ABSTRACT: Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca(2+)]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine and spermine levels. 5 mM difluoromethylornithine (DFMO) and 1 mM methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. 10 µM OXO was used to increase [Ca(2+)]i levels (measured by fura-2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared to NB BUC (0.5±0.15 vs 0.16±0.03 nmol/mg for putrescine, 2.4±0.21 vs 1.01±0.13 nmol/mg for spermidine, 1.90±0.27 vs 0.86±0.26 nmol/mg for spermine, p<0.05 for all comparisons). OXO evoked greater [Ca(2+)]i rise in OAB (205.10%±18.82% increase over baseline) compared to in NB BUC (119.54%±13.01%, p<0.05). After polyamine depletion, OXO evoked [Ca2+]i rise decreased in OAB and NB BUC to 43.40% ±6.45% and 38.82%±3.5%, respectively. OXO tended to increase ACh release by OAB versus NB BUC (9.02±0.1 versus 7.04±0.09 µM, respectively, p<0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated 2 fold in OAB BUC. OXO evoked greater increase in [Ca2+]i and ACh release in OAB BUC, though these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC.
AJP Renal Physiology 05/2013; · 4.42 Impact Factor
-
Michael E Albo,
Heather J Litman,
Holly E Richter,
Gary E Lemack,
Larry T Sirls, Toby C Chai,
Peggy Norton,
Stephen R Kraus,
Halina Zyczynski,
Kimberly Kenton,
E Ann Gormley,
John W Kusek
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: Longer term comparative efficacy information regarding transobturator and retropubic mid urethral slings is needed. We report 24-month continence rates, complications and symptom outcomes from a randomized equivalence trial. MATERIALS AND METHODS: Primary outcomes were objective (negative stress test, negative pad test and no re-treatment for stress urinary incontinence) and subjective (no self-report of stress urinary incontinence symptoms, no leakage episodes on 3-day bladder diary and no re-treatment for stress urinary incontinence) success at 24 months. The predetermined equivalence margin was ±12%. RESULTS: Of 597 randomized participants 516 (86.4%) were assessed. Objective success rates for retropubic and transobturator mid urethral slings were 77.3% and 72.3%, respectively (95% CI for difference of 5.1% was -2.0, 12.1), and subjective success rates were 55.7% and 48.3%, respectively (CI for difference of 7.4% was -0.7, 15.5). Neither objective nor subjective success rates met the prespecified criteria for equivalence. Patient satisfaction (retropubic 86.3% vs transobturator 88.1%, p = 0.58), frequency of de novo urgency incontinence (retropubic 0% vs transobturator 0.3%, p = 0.99) and occurrence of mesh exposure (retropubic 4.4% vs transobturator 2.7%, p = 0.26) were not significantly different. The retropubic mid urethral sling group had higher rates of voiding dysfunction requiring surgery (3.0% vs 0%, p = 0.002) and urinary tract infections (17.1% vs 10.7%, p = 0.025), whereas the transobturator group had more neurological symptoms (9.7% vs 5.4%, p = 0.045). CONCLUSIONS: Objective success rates met the criteria for equivalence at 12 months but no longer met these criteria at 24 months. Subjective success rates remained inconclusive for equivalence. Patient satisfaction remained high and symptom severity remained markedly improved. Continued surveillance is important in women undergoing mid urethral sling surgery.
The Journal of urology 10/2012; · 4.02 Impact Factor
-
Holly E Richter,
Linda Brubaker,
Anne M Stoddard,
Yan Xu,
Halina M Zyczynski,
Peggy Norton,
Larry T Sirls,
Stephen R Kraus, Toby C Chai,
Philippe Zimmern,
E Ann Gormley,
John W Kusek,
Michael E Albo
[show abstract]
[hide abstract]
ABSTRACT: We examined preoperative and postoperative patient related factors associated with continence status up to 7 years after surgery for stress urinary incontinence.
Women randomized to Burch colposuspension or fascial sling surgery and assessed for the primary outcome of urinary continence 2 years after surgery were eligible to enroll in a prospective observational study. Survival analysis was used to investigate baseline and postoperative factors in the subsequent risk of stress urinary incontinence, defined as self-report of stress urinary incontinence symptoms, incontinence episodes on a 3-day diary or surgical re-treatment.
Of the women who participated in the randomized trial 74% (482 of 655) were enrolled in the followup study. Urinary continence rates decreased during a period of 2 to 7 years postoperatively from 42% to 13% in the Burch group and from 52% to 27% in the sling group, respectively. Among the baseline factors included in the first multivariable model age (p = 0.03), prior stress urinary incontinence surgery (p = 0.02), menopausal status (0.005), urge index (0.006), assigned surgery (p = 0.01) and recruiting site (p = 0.02) were independently associated with increased risk of incontinence. In the final multivariable model including baseline and postoperative factors, Burch surgery (p = 0.01), baseline variables of prior urinary incontinence surgery (p = 0.04), menopausal status (p = 0.03) and postoperative urge index (p <0.001) were each significantly associated with a greater risk of recurrent urinary incontinence.
Preoperative and postoperative urgency incontinence symptoms, Burch urethropexy, prior stress urinary incontinence surgery and menopausal status were negatively associated with long-term continence rates. More effective treatment of urgency urinary incontinence in patients who undergo stress urinary incontinence surgery may improve long-term overall continence status.
The Journal of urology 06/2012; 188(2):485-9. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIM: To examine function of both cholinergic (muscarinic) and TRPV1 receptors in human bladder urothelial (HBUC) from non-neurogenic overactive bladder (OAB) patients as compared to control subjects. METHODS: Primary HBUC cultures were derived from cystoscopic biopsies from OAB and control subjects. Muscarinic and TRPV1 function was assessed by acetylcholine (5 μm) or capsaicin (0.5 μm) evoked ATP release, measured by luciferase assay. Overall, expression of TRPV1 and muscarinic M3 receptors in bladder urothelial cells was accomplished using western immunoblotting. RESULTS: Our findings revealed that the response to acetylcholine in OAB HBUC cultures (which was blocked by the nonselective muscarinic antagonist, atropine methyl nitrate or AMN) was not significantly different than from controls. The acetylcholine M3 receptor was slightly decreased as compared to control. In contrast, OAB HBUC cultures exhibited a capsaicin hypersensitivity and augmented release of ATP (3.2 fold higher), which was blocked by the antagonist capsazepine. The increase in capsaicin sensitivity correlated with increased urothelial TRPV1 expression. CONCLUSION: Though characterized in a small number of subjects, augmented release of urothelial-derived transmitters such as ATP could 'amplify' signalling between and within urothelial cells and nearby afferent nerves.
Acta Physiologica 06/2012; · 3.09 Impact Factor
-
Charles W Nager,
Linda Brubaker,
Heather J Litman,
Halina M Zyczynski,
R Edward Varner,
Cindy Amundsen,
Larry T Sirls,
Peggy A Norton,
Amy M Arisco, Toby C Chai, [......],
Elizabeth Mueller,
Gary Sutkin,
Tracey S Wilson,
Yvonne Hsu,
Thomas A Rozanski,
Leslie M Rickey,
David Rahn,
Sharon Tennstedt,
John W Kusek,
E Ann Gormley
[show abstract]
[hide abstract]
ABSTRACT: Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes.
We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points.
A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, -0.3 percentage points; 95% confidence interval, -7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes.
For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.).
New England Journal of Medicine 05/2012; 366(21):1987-97. · 53.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ureteral injury or compromise can occur after pelvic floor reconstruction for prolapse. Therefore, it is routine to perform intraoperative urethrocystoscopy at end of the operative case to confirm ureteral patency. We show retrograde ureterogram before and after release of fixation sutures from bilateral sacrospinous ligament fixation performed for stage III vaginal prolapse. The fluoroscopic images presented are intended to help pelvic surgeons visualize what could occur during sacrospinous ligament fixation. Furthermore, this case report illustrates how angulation of the distal ureter, without complete obstruction, may result in renal compromise.
Journal of Pelvic Medicine and Surgery 05/2012; 18(3):168-9.
-
[show abstract]
[hide abstract]
ABSTRACT: To determine whether concomitant surgeries affected outcomes in a randomized trial comparing retropubic midurethral sling (MUS) vs transobturator MUS.
Subjects (n = 597) were stratified into 4 groups based on type of concomitant surgeries: group I had anterior/apical with or without posterior repairs (n = 79, 13%); group II had posterior repairs or perineorrhaphy only (n = 38, 6%); group III had nonprolapse procedures (n = 34, 6%); and group IV had no concomitant surgeries (n = 446, 75%). Complication rates, voiding dysfunction, objective and subjective surgical failure rates, and changes in urodynamic values (postop minus preop) were assessed and compared in these 4 groups.
There were no differences in complications, voiding dysfunction, and subjective failure outcomes between these 4 groups. Group I had lower odds ratio of objective surgical failure compared with group IV (OR 0.38, 95% CI 0.18-0.81, P = .05). The OR of failure of all patients undergoing concomitant surgeries (groups I-III) was lower than group IV (OR 0.57, 95% CI 0.35-0.95, P = .03). The change in Pdet@Qmax (from pressure-flow) was significantly higher in group III vs IV (P = .01). The change in Q(max.) (from uroflowmetry) was significantly less in groups I and II vs group IV (P = .046 and .04, respectively).
Concomitant surgeries did not increase complications. Subjects who underwent certain concomitant surgeries had lower failure rates than those undergoing slings only. These data support safety and efficacy of performing concomitant surgery at the time of MUS.
Urology 04/2012; 79(6):1256-61. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore how baseline demographic, clinical, and urodynamic (UDS) variables correlate with measures of urethral function in women planning midurethral sling surgery.
Women with predominant stress urinary incontinence (SUI) as part of the trial of mid-urethral slings (TOMUS) were characterized preoperatively including: demographics, body mass index (BMI), responses to the Medical and Epidemiologic Social Aspects of Aging (MESA) and Urogenital Distress Inventory (UDI) questionnaires, pad weight (PW), incontinence duration, prior SUI surgery, prolapse, strength of pelvic contraction, Q-tip test, uroflow, cystometrogram, and detrusor pressures at maximum flow (Pdet at Qmax). Multivariate regression analysis and modeling confirmed variables with significant correlations with maximal urethral closure pressure (MUCP), functional urethral length (FUL), and Valsalva leak point pressure (VLPP).
Five-hundred thirty-nine women were included in the analysis. In multivariable analyses, PW (P = 0.045) and age (P < 0.0001) were negatively correlated with MUCP (as PW and age increased, MUCP decreased); BMI (P = 0.02) and Pdet at Qmax (P < 0.0001) were positively correlated with MUCP (as BMI and Pdet at Qmax increased, MUCP increased). Age (P = 0.002) was negatively correlated with FUL; Qtip delta (P = 0.006), pelvic organ prolapse quantification examination (POPQ) stage (P = 0.002) and strength of pelvic contraction (P = 0.03) were positively correlated with FUL. Duration of incontinence (P = 0.01) was negatively correlated with VLPP; Qtip delta (P = 0.02), BMI (P = 0.0005) and Pdet at Qmax (P = 0.0005) were positively correlated with VLPP.
Age, BMI, Qtip delta, and Pdet at Qmax were variables that correlated with two or more measures of urethral function. These correlations may help direct future research in female urethral function.
Neurourology and Urodynamics 02/2012; 31(4):496-501. · 2.96 Impact Factor
-
Stephen R Kraus,
Gary E Lemack,
Holly E Richter,
Linda Brubaker, Toby C Chai,
Michael E Albo,
Larry T Sirls,
Wendy W Leng,
John W Kusek,
Peggy Norton,
Heather J Litman
[show abstract]
[hide abstract]
ABSTRACT: To characterize the urodynamic (UDS) changes in subjects 24 months after Burch urethropexy and autologous fascial sling surgery for stress urinary incontinence.
In the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr), 655 women underwent standardized UDSs before and 2 years after Burch or sling surgery. Paired t tests were used to compare the pre- and postoperative UDS measures by treatment group. Analysis of variance models were fit predicting the change in UDS measures, controlling for the treatment group.
The noninstrumented maximal flow rate decreased 3.6 mL/s in the Burch group and 4.7 mL/s in the sling group (P = .42). The average flow rates also decreased (2.4 mL/s in the Burch group and 3.8 mL/s in the sling group, P = .039). No difference was found in the increases in first sensation between the Burch and sling groups (23.3 and 29.3 mL, respectively, P = .61). Also, no differences were found in the reduction in the pressure flow study maximal flow rates (2.3 mL/s in the Burch group and 4.4 mL/s in the sling group, P = .11). An increased detrusor pressure at maximal flow rate (11.4 cm H(2)O, P < .001) was seen only after the sling procedure. Increases in the bladder outlet obstruction index occurred after both procedures, with greater increases seen after sling surgery (change, Burch +6.27 vs sling +20.12, P = .001).
The Burch colposuspension and autologous fascial sling procedures were associated with similar decreases in noninstrumented flow rates, and the sling was associated with greater increases in the detrusor pressure at maximal flow rate and bladder outlet obstruction index. These changes suggest that both procedures are effective, in part, because of increased outlet resistance. However, the sling procedure might be more obstructive.
Urology 12/2011; 78(6):1263-8. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To identify urodynamic changes that correlate with successful outcomes after stress urinary incontinence (SUI) surgery.
Six-hundred fifty-five women were randomized to Burch colposuspension or autologous fascial sling as part of the multicenter Stress Incontinence Surgical Treatment Efficacy Trial. Preoperatively and 24 months after surgery, participants underwent standardized urodynamic testing that included noninvasive uroflowmetry, cystometrogram, and pressure flow studies. Changes in urodynamic parameters were correlated to a successful outcome, defined a priori as (1) negative pad test; (2) no urinary incontinence on 3-day diary; (3) negative cough and Valsalva stress test; (4) no self-reported SUI symptoms on the Medical, Epidemiologic and Social Aspects of Aging Questionnaire; and (5) no re-treatment for SUI.
Subjects who met criteria for surgical success showed a greater relative increase in mean Pdet@Qmax (baseline vs 24 months) than women who were considered surgical failures (P = .008). Although a trend suggested an association between greater increases in bladder outlet obstruction index and outcome success, this was not statistically significant. Other urodynamic variables, such as maximum uroflow, bladder compliance, and the presence of preoperative or de novo detrusor overactivity did not differ with respect to outcome status.
Successful outcomes in both surgical groups (Burch and sling) were associated with higher voiding pressures relative to preoperative baseline values. However, concomitant changes in other urodynamic voiding parameters were not significantly associated with outcome.
Urology 12/2011; 78(6):1257-62. · 2.43 Impact Factor
-
Toby C Chai
Current Bladder Dysfunction Reports 09/2011; 6(3):114-115.
-
Linda Brubaker,
Peggy A Norton,
Michael E Albo, Toby C Chai,
Kimberly J Dandreo,
Keith L Lloyd,
Jerry L Lowder,
Larry T Sirls,
Gary E Lemack,
Amy M Arisco,
Yan Xu,
John W Kusek
[show abstract]
[hide abstract]
ABSTRACT: To describe surgical complications in 597 women over a 24-month period after randomization to retropubic or transobturator midurethral slings.
During the Trial of Midurethral Slings study, the Data Safety Monitoring Board regularly reviewed summary reports of all adverse events using the Dindo Surgical Complication Scale. Logistic regression models were created to explore associations between clinicodemographic factors and surgical complications.
A total of 383 adverse events were observed among 253 of the 597 women (42%). Seventy-five adverse events (20%) were classified as serious (serious adverse events); occurring in 70 women. Intraoperative bladder perforation (15 events) occurred exclusively in the retropubic group. Neurologic adverse events were more common in the transobturator group than in retropubic (32 events vs 20 events, respectively). Twenty-three (4%) women experienced mesh complications, including delayed presentations, in both groups.
Adverse events vary by procedure, but are common after midurethral sling. Most events resolve without significant sequelae.
American journal of obstetrics and gynecology 07/2011; 205(5):498.e1-6. · 3.28 Impact Factor
-
Ingrid Nygaard,
Linda Brubaker, Toby C Chai,
Alayne D Markland,
Shawn A Menefee,
Larry Sirls,
Gary Sutkin,
Phillipe Zimmern,
Amy Arisco,
Liyuan Huang,
Sharon Tennstedt,
Anne Stoddard
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to describe risk factors for post-operative urinary tract infection (UTI) the first year after stress urinary incontinence surgery.
Multivariable logistic regression analyses were performed on data from 1,252 women randomized in two surgical trials, Stress Incontinence Surgical Treatment Efficacy trial (SISTEr) and Trial Of Mid-Urethral Slings (TOMUS).
Baseline recurrent UTI (rUTI; ≥3 in 12 months) increased the risk of UTI in the first 6 weeks in both study populations, as did sling procedure and self-catheterization in SISTEr, and bladder perforation in TOMUS. Baseline rUTI, UTI in the first 6 weeks, and PVR > 100 cc at 12 months were independent risk factors for UTI between 6 weeks and 12 months in the SISTEr population. Few (2.3-2.4%) had post-operative rUTI, precluding multivariable analysis. In women with pre-operative rUTI, successful surgery (negative cough stress test) at 1 year did not appear to decrease the risk of persistent rUTI.
Pre-operative rUTI is the strongest risk factor for post-operative UTI.
International Urogynecology Journal 05/2011; 22(10):1255-65. · 1.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Minimum important difference (MID) estimates the minimum degree of change in an instrument's score that correlates with subjective sense of improvement. The aim of this study was to estimate the MID for the Urogenital Distress Inventory (UDI), Incontinence Impact Questionnaire (IIQ) and Overactive Bladder Questionnaire (OAB-q) using anchor and distribution-based approaches in patients with urge-predominant incontinence and whether MID changes over time.
This was a sub-analysis of a multi-center trial of 307 women with pure urge (11) or urge-predominant (296) incontinence who completed condition-specific instruments 10 weeks and 8 months after randomization to anticholinergic medication with or without behavioral therapy. We applied anchor-based methods only when the Kendall's rank correlations between the anchors (Global Perception of Improvement (GPI), Patient Satisfaction Questionnaire (PSQ), and incontinence episodes) and the incontinence instruments (UDI, UDI irritative subscale, IIQ, and OAB-q subscales) were ≥ 0.3. We applied three distribution-based methods to all instruments: effect sizes of ± 0.2 SD (small) and ± 0.5 SD (medium), and standard error of measurement of ± 1. Analyses were performed at both time points.
Anchor-based MIDs for the UDI ranged from -35 to -45 and -15 to -25 for the irritative subscale distribution-based methods MIDs for UDI and IIQ ranged between -10 to -25 and -19 to -49, respectively, reflective of a reduction in bother and symptom severity (SS). OAB-q subscale MIDs ranged from +5 to +12, denoting improved quality of life (HRQL) and -13 to -25, consistent with a reduction in SS.
The MID in women with urge-predominant UI for the UDI and UDI irritative are -35 and -15. Our findings are consistent with previously reported MIDs for the OAB-q subscales. Distribution-based method MIDs are lower values than anchor-based values. The MID did not typically change over the time.
Neurourology and Urodynamics 05/2011; 30(7):1319-24. · 2.96 Impact Factor
-
Claire C Yang,
David A Burks,
Kathleen J Propert,
Robert D Mayer,
Kenneth M Peters,
J Curtis Nickel,
Christopher K Payne,
Mary P FitzGerald,
Philip M Hanno, Toby C Chai,
Karl J Kreder,
Emily S Lukacz,
Harris E Foster,
Liyi Cen,
J Richard Landis,
John W Kusek,
Leroy M Nyberg
[show abstract]
[hide abstract]
ABSTRACT: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome.
A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries.
Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls.
In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.
The Journal of urology 03/2011; 185(3):901-6. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To test the hypothesis that hypoxia plays a role in overactive bladder (OAB) symptoms by studying how the in vitro stretch of primary cultured bladder urothelial cells (BUCs) from those with OAB and asymptomatic subjects altered the expression of angiogenic factors. The angiogenic factors included hypoxia-inducible factor-1 alpha subunit (HIF-1α), HIF-2 alpha subunit (HIF-2α), and vascular endothelial growth factor (VEGF).
HIF-1α, HIF-2α, and VEGF mRNA expression were analyzed using real-time quantitative polymerase chain reaction. Fluorescence-activated cell sorting was used to measure the protein expression. The release of VEGF in the supernatant of stretched OAB and normal BUCs was measured using enzyme-linked immunosorbent assay.
Stretching of OAB BUCs increased the expression of mRNA for HIF-1α, HIF-2α, and VEGF by 1.5-fold (P < .01), 1.5-fold (P < .01), and 3.5-fold (P < .001) compared with unstretched OAB BUCs. This augmentation was not detected when comparing stretched normal BUCs with unstretched normal BUCs. Using fluorescence-activated cell sorting quantitation, only HIF-2α was significantly increased (P < .01). Measuring VEGF in the supernatant revealed that stretched OAB BUCs released significantly more VEGF than nonstretched OAB BUCs at multiple points. In contrast, stretched normal BUCs did not release VEGF.
OAB BUCs responded to stretch by expressing increased angiogenic markers, HIF-1α, HIF-2α, and/or VEGF, measured at the transcript and protein levels. This suggests that OAB BUCs respond as if they were primed by hypoxia. This knowledge adds to the pathophysiologic understanding of OAB.
Urology 03/2011; 77(5):1266.e7-11. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To measure transient receptor potential vanilloid type 1 (TRPV1) signaling in human bladder urothelial cells (BUC) from non-neurogenic overactive bladder (OAB) patients and control subjects (NB) BUC.
Primary BUC cell cultures were derived from cystoscopic biopsies from two OAB and two NB subjects. TRPV1 expression was detected by immunofluorescence, PCR and Western blot staining. TRPV1 function was assessed by capsaicin (CAP, 6 µM)-evoked intracellular calcium ([Ca(2+)](i)) changes measured by microfluorimetry imaging. CAP evoked changes in inward and outward currents were recorded electrophysiologically using excised outside-out patches and whole cell configurations using various protocols.
OAB BUC had significantly increased expression of TRPV1 compared to NB BUC on Western blot. CAP evoked significantly higher maximal [Ca(2+)](i) change over baseline in OAB (84.71 ± 8.96%) compared to NB BUC (60.32 ± 7.93%) (P < 0.05). CAP induced significantly greater percent change in single channel open probability (205.94 ± 20.53% OAB vs. 141.26 ± 16.53% NB, P < 0.05) and normalized inward currents (13.54 ± 1.6 4 pA/pF OAB vs. 8.28 ± 0.89 pA/pF NB, P < 0.05). CAP caused significantly higher percent increase from baseline of whole cell outward currents in OAB (177.12 ± 44.46%) compared to NB BUC (135.98 ± 44.28%) (P < 0.05). Similarly thermal stimulus (45°C solution) evoked significantly higher percent increase in whole cell outward currents in OAB (183.93 ± 14.07%) compared to NB (145.61 ± 10.12%) BUC (P < 0.05). These responses were blocked by 10 µM capsazepine (CPZ), a TRPV1 antagonist.
Because only a few subjects were studied, augmented TRPV1 signaling cannot be generalized to all OAB subjects. However, the findings are consistent with the hypothesis that BUC are involved in sensory signaling.
Neurourology and Urodynamics 02/2011; 30(4):606-11. · 2.96 Impact Factor
-
Journal of Pelvic Medicine and Surgery 01/2011; 17(1):4-7.
-
[show abstract]
[hide abstract]
ABSTRACT: We hypothesized that certain preoperative voiding symptoms would be correlated with poorer post-continence surgery outcomes in women.
Preoperative voiding symptoms from 655 women were assessed with questionnaires. Outcomes (overall failures, stress-specific failures, and voiding dysfunction) after Burch or sling surgery were measured. Logistic regression models were used to associate preoperative voiding symptoms with postoperative outcomes.
Hesitating urinary stream was associated with voiding dysfunction [OR 2.22, p=0.01], overall [OR 1.57, p=0.03], and stress-specific [OR 1.67, p=0.009] failures. A ten-point increase in preoperative Urogenital Distress Inventory-obstructive (UDI-O) subscore was associated with overall [OR 1.10, p=0.049] and stress-specific [OR 1.21, p<0.0001] failures. Even controlling for severity of POPQ stage, significant associations of hesitating urinary stream with voiding dysfunction, overall and stress-specific failures remained.
Preoperative hesitating urinary stream and obstructive voiding symptoms were associated with poorer surgical outcomes. Further studies in this area may be fruitful.
International Urogynecology Journal 12/2010; 22(6):713-9. · 1.83 Impact Factor
-
Charles W Nager,
Stephen R Kraus,
Kim Kenton,
Larry Sirls, Toby C Chai,
Clifford Wai,
Gary Sutkin,
Wendy Leng,
Heather Litman,
Liyuan Huang,
Sharon Tennstedt,
Holly E Richter
[show abstract]
[hide abstract]
ABSTRACT: Determine whether urodynamic measures of urethral function [(valsalva leak point pressure (VLPP), maximum urethral closure pressure (MUCP), functional urethral length (FUL)] and the results of the supine empty bladder stress test (SEBST) correlate with each other and with subjective and objective measures of urinary incontinence (UI).
Data were collected preoperatively from subjects enrolled in a multicenter surgical trial of mid-urethral slings. Subjective measures included questionnaire scores from the Medical Epidemiological and Social Aspects of Aging Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. Objective measures included a 24-hr pad weight test, incontinence episode frequency on a 3-day voiding diary, and a SEBST.
Five hundred ninety-seven women enrolled. Three hundred seventy-two women had valid VLPP values; 539 had valid MUCP/FUL values. Subjective measures of severity had weak to moderate correlation with each other (r = 0.25-0.43) and with objective measures of severity (r = -0.06 to 0.45). VLPP and MUCP had moderate correlation with each other (r = 0.36, P< 0.001). Urodynamic measures of urethral function had little or no correlation with subjective or objective measures of severity. Subjects with a positive SEBST had more subjective and objective severity measures compared to the negative SEBST group, but they did not have significantly different VLPP and MUCP values.
VLPP and MUCP have moderate correlation with each other, but each had little or no correlation with subjective or objective measures of severity or with the results of the SEBST. This data suggests that the urodynamic measures of urethral function are not related to subjective or objective measures of UI severity.
Neurourology and Urodynamics 09/2010; 29(7):1306-11. · 2.96 Impact Factor
