A randomized, pilot trial comparing vaginal hyaluronic acid to vaginal estrogen for the treatment of genitourinary syndrome of menopause.

OBJECTIVE: The aim of this study was to compare the efficacy of a non-hormone alternative, vaginal hyaluronic acid (HLA), to a standard-of-care therapy, vaginal estrogen, for the treatment of genitourinary syndrome of menopause (GSM). METHODS: This was a randomized, parallel arm pilot trial. Women with GSM were randomized to an HLA vaginal suppository or vaginal estrogen cream for 12 wk to compare the primary outcome, the vulvovaginal symptom questionnaire (VSQ) score. Secondary outcomes included the following: the female sexual function index (FSFI), the vaginal symptom index (VSI), visual analog scale (VAS) for dyspareunia, vaginal itching, and vaginal dryness, patient global impression of improvement (PGI-I) at follow-up, vaginal maturation index, and vaginal pH. Differences between treatment groups were estimated using the two-sided, two-sample t -test and 95% confidence intervals. RESULTS: Forty-nine women were randomized and 45 participants (vaginal estrogen = 23, vaginal HLA = 22) provided data at week 12. Baseline characteristics were similar in both groups. On the VSQ, there was no observed difference in overall scores between the HLA and vaginal estrogen groups at 12 wk ( P = 0.81). Improvement was seen within both treatment groups on the VSQ after 12 wk. The VAS score, total VSI score, total FSFI score, and vaginal pH improved over time; however, improvement did not differ between study arms. Over 90% participants noted improvement on the PGI-I in both groups ( P = 0.61). No treatment-related serious adverse events occurred. CONCLUSIONS: There were no clinically meaningful differences between vaginal HLA and vaginal estrogen for the treatment of GSM after 12 wk. Vaginal HLA may be a promising non-hormone therapy for GSM.

Predictors of Care-Seeking Behavior for Treatment of Urinary Incontinence in Women.

IMPORTANCE: Urinary incontinence (UI) is a common and treatable medical condition among women, but only approximately one third of women seek care. OBJECTIVE: The objective of this study was to determine factors associated with care-seeking behavior in women with UI. STUDY DESIGN: This was a cross-sectional study using patient-reported survey data collected by the National Association for Continence from November 2018 to January 2019. This survey included 60 questions and was conducted using SurveyMonkey. Descriptive statistics were used for baseline characteristics, the χ2 test was used for categorical variables, and multivariate logistic regression was used to determine predictors of care-seeking behavior. RESULTS: Four hundred eighty-five women completed the survey, 30.7% were not care seeking, and 69.3% were care seeking for UI. Most women were 55 years or older and had UI for more than 4 years. Care-seeking women had more overactive bladder symptoms. Women who sought care were more likely to report feelings of anger, depression, hopelessness, isolation, and report greater social effects from UI than non-care-seeking women. Less than 10% of women who sought care were asked about their UI by a medical professional. In the multivariate logistic regression expenditure of $5 or more on monthly incontinence maintenance, daily UI and older age were associated with seeking care. CONCLUSIONS: Most women in our study population sought care for UI. Factors associated with seeking care were expenditure greater than $5 per month on incontinence, daily UI, and age. This information demonstrates the need for effective implementation of screening interventions to increase treatment access.

Analyzing Access and Costs of Oral Medications for Overactive Bladder: Uncovering Disparities.

OBJECTIVE: To report out-of-pocket costs associated with overactive bladder (OAB) medications among Medicare beneficiaries and the uninsured. METHODS: We performed a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data (Q1-2022). FDA-approved medications for OAB were identified. We calculated out-of-pocket costs for Medicare beneficiaries in each Part D prescription benefit phase, average retail price, total yearly costs and discounted prices through cash-pay discount coupons (GoodRx) or online pharmacies like Mark Cuban Cost Plus Drug Company (MCCPDC). We also report plan utilization management requirements. RESULTS: We analyzed 5721 plan formularies for 18 medications. Mirabegron was the only beta-3 agonist (B3). Only Vesicare oral solution (14.3% of plans) and Mirabegron (0.1%) required prior authorization. Many plans required step therapy for selective generic anticholinergics (ACH) (12.4%-43.3%), while the B3 rarely required step therapy (0.6%). Monthly costs varied by coverage phase and averaged $59 for ACHs in the initial coverage phase ($14 in catastrophic; $72 in coverage gap). The monthly cost for the B3 averaged $47 in the initial coverage phase ($26 in catastrophic; $129 in coverage gap). The total yearly cost for generic ACHs ranged from $494 (oxybutynin IR) to $1452 (darifenacin) and the yearly cost for brand-name ACHs ranged from $1175 (Toviaz ER) to $2198 (Oxytrol). The total yearly cost for the B3 was $1283. CONCLUSION: We evaluated coverage, out-of-pocket costs, total yearly costs, and utilization management for OAB medications to make pricing more transparent. While selective medications may be "covered," coverage does not translate into affordable drug prices.

The PSR13, a tool for evaluating patient-perceived recovery after vaginal prolapse repair surgery.

INTRODUCTION AND HYPOTHESIS: Surgical recovery is the return to preoperative functional, psychologic, and social activity, or a return to normalcy. To date, little is known about the global post-surgical recovery experience from the patients' perspective. The aim of this study was to validate the Post-Discharge Surgical Recovery scale 13 (PSR13) in women undergoing vaginal prolapse repair procedures and evaluate the patient-perceived postoperative recovery experience over a 12-week period. METHODS: Fifty women undergoing vaginal prolapse repairs completed the PSR13 and global surgical recovery scale (GSR) at 1, 2, 4, 6, and 12 weeks post-surgery. Validity, the minimal clinically important difference (MCID), and responsiveness to change over time of the PSR13 was evaluated using descriptive statistics and linear regression models. The proportion of patients deemed fully recovered at each time point (defined as PSR13 score ≥ 80) was also assessed. RESULTS: The PSR13 correlated significantly (p < 0.001) with the single-item recovery scale and showed excellent internal consistency reliability (Cronbach α = 0.91, range 0.77 to 0.93). The MCID was estimated at 7.0 points. The PSR13 scores improved at varying rates over time, with the greatest amount of patient-perceived recovery occurring between 4 and 6 weeks after surgery. The proportion of patients deemed fully recovered at 6- and 12- weeks postoperatively was 37% and 56%, respectively. CONCLUSIONS: The PSR13 is a useful instrument to assess overall return to normalcy from the patient's perspective and can be applied to evaluate the recovery experience among women undergoing vaginal prolapse repairs, in both the research and clinical setting.

Estimation of Urinary Frequency: Does Question Phrasing Matter?

PURPOSE: To evaluate if question phrasing and patient numeracy impact estimation of urinary frequency. MATERIALS AND METHODS: We conducted a prospective study looking at reliability of a patient interview in assessing urinary frequency. Prior to completing a voiding diary, patients estimated daytime, and nighttime frequency in 3 ways: (1) how many times they urinated (2) how many hours they waited in between urinations (3) how many times they urinated over the course of 4 hours. Numeracy was assessed using the Lipkus Numeracy Scale. RESULTS: Seventy-one patients completed the study. Correlation of estimates from questions 1, 2, and 3 to the diary were not statistically different. Prediction of nighttime frequency was better than daytime for all questions (correlation coefficients 0.751, 0.754, and 0.670 vs 0.596, 0.575, and 0.460). When compared to the diary, Question 1 underestimated (8.5 vs 9.7, P = .014) while Question 2 overestimated (11.8 vs 9.7, P = .027) recorded voids on a diary. All questions overpredicted nighttime frequency with 2.6, 2.9, and 3.9 predicted versus 1.6 recorded voids (P < .001). Although not statistically significant, for each question, the predicted frequency of numerate patients was more correlated to the diary than those of innumerate patients. CONCLUSION: When compared to a voiding diary for daytime urinary frequency, asking patients how many times they urinated underestimated, and asking patients how many hours they waited between urinations overestimated the number recorded voids. Regardless of phrasing, patients overestimated nighttime urination. Patients in our functional urology population have limited numeracy, which may impact accuracy of urinary frequency estimation.

Rethinking Second-Line Therapy for Overactive Bladder to Improve Patient Access to Treatment Options.

Idiopathic overactive bladder (OAB) is a chronic condition that negatively affects quality of life, and oral medications are an important component of the OAB treatment algorithm. Recent literature has shown that anticholinergics, the most commonly prescribed oral medication for the treatment of OAB, are associated with cognitive side effects including dementia. ß3-adrenoceptor agonists, the only alternative oral treatment for OAB, are similar in efficacy to anticholinergics with a more favorable side effect profile without the same cognitive effects. However, there are marked cost variations and barriers to access for OAB medications, resulting in expensive copays and medication trial requirements that ultimately limit access to ß3-adrenoceptor agonists and more advanced procedural therapies. This contributes to and perpetuates health care inequality by burdening the patients with the least resources with a greater risk of dementia. When prescribing these medications, health care professionals are caught in a delicate balancing act between cost and patient safety. Through multilevel collaboration, we can help disrupt health care inequalities and provide better care for patients with OAB.

Vaginal Estrogen-What a Urologist Should Know.

The implications of estrogen depletion on the lower urinary tract and vagina are relevant to the urologist treating women with genitourinary symptoms. The main symptoms of vaginal estrogen depletion that affect women are dyspareunia and vaginal dryness, recurrent urinary tract infection, and lower urinary tract symptoms. Vaginal estrogen can be used to effectively treat these conditions. Vaginal estrogen is available in a variety of formulations. Each formulation has different considerations regarding its use and patients should be actively involved in choosing the right product for them. Contrary to concerns over the risks of oral estrogen, vaginal estrogen has a low-risk profile. In terms of contra-indications for use, there are relatively few absolute contraindications for vaginal estrogen. A thorough understanding of vaginal estrogen's safety, efficacy and correct use is essential to the urologist treating the post-menopausal female.

Venous thromboembolism prophylaxis in vaginal surgery for pelvic organ prolapse: Predictors of high risk in a low-risk population.

AIM: Venous thromboembolism (VTE) rates in vaginal pelvic organ prolapse (POP) repair are low. Our aim is to evaluate specific risk factors for VTE in patients undergoing vaginal POP repair. METHODS: This is a cross-sectional study using the American College of Surgeons NSQIP database. Using CPT codes, cases of vaginal POP repair between 2014 and 2017 were identified. Patient and operative characteristics were collected. VTE was defined as pulmonary embolism (PE) or deep vein thrombosis (DVT) within 30 days from surgery. Univariate analyses were performed using the Student t test for continuous and χ2  tests for categorical variables. Multivariate logistic regression was performed to identify factors independently associated with VTE. RESULTS: Of 44 207 women who underwent vaginal POP repair, there were 69 cases of VTE (0.16%). VTE rates for obliterative (0.15%) and functional (0.16%) vaginal POP repair, as well as for repairs with hysterectomy (0.17%) and without hysterectomy (0.12%) were not significantly different (p = .616 and .216, respectively). Multivariate analysis demonstrated predictors for postoperative VTE to be ASA physical status classification ≥ 3 (aOR, 1.99; p = .014), length of stay >75th percentile (aOR, 2.01; p = .007), operative time >3 h (aOR, 2.24; p = .007), and dyspnea (aOR, 3.26, p = .004). CONCLUSION: Despite the low incidence of VTE after vaginal POP repair, patients with ASA physical status classification ≥ 3, length of stay >75th percentile, operative time >3 h, and dyspnea were at higher risk for VTE. Vaginal POP repair may have independent VTE risk factors not captured in standard risk assessment tools.

The impact of concomitant mid-urethral sling surgery on patients undergoing vaginal prolapse repair.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess whether mid-urethral sling (MUS) placement at the time of vaginal prolapse repair compared to vaginal prolapse repair alone is associated with an increase in 30-day postoperative complications. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Database, Current Procedural Terminology codes were used to identify cases of vaginal prolapse repair with and without concomitant MUS from 2012 to 2017. Student's t-test and chi-square test were used to compare differences between the groups. RESULTS: A total of 1469 cases of vaginal prolapse repair with sling were compared to 4566 cases without sling. There was no difference between prolapse repair with sling compared to without sling in mean hospital length of stay (LOS) (1.42 versus 1.32 days, p = 0.65), postoperative urinary tract infection (UTI) (6.1% versus 5.8%, p = 0.670), perioperative blood transfusion (1.1% versus 1.2%, p = 0.673), readmission (2.7% versus 2.6%, p = 0.884) and postoperative wound infection (0.5% versus 0.7%, p = 0.51). There was a higher rate of reoperation (2.2% versus 1.5%, p = 0.049) and venous thromboembolism (VTE) (0.4% versus 0.1%, p = 0.030) in patients undergoing concomitant MUS compared to those undergoing prolapse repair alone. CONCLUSIONS: Compared to prolapse repair alone, the addition of a sling did not increase hospital LOS, UTI, perioperative blood transfusions, readmission or postoperative wound infections. However, concomitant sling was found to be associated with a higher risk of reoperation and VTE.

A multicenter retrospective cohort study comparing urethral diverticulectomy with and without pubovaginal sling.

BACKGROUND: Urethral diverticulum is a rare entity and requires a high suspicion for diagnosis based on symptoms and physical exam with confirmation by imaging. A common presenting symptom is stress urinary incontinence (SUI). The recommended treatment is surgical excision with urethral diverticulectomy. Postoperatively, approximately 37% of patients may have persistent and 16% may have de novo SUI. An autologous fascial pubovaginal sling (PVS) placed at the time of urethral diverticulectomy (UD) has the potential to prevent and treat postoperative SUI. However, little has been published about the safety and efficacy of a concomitant pubovaginal sling. OBJECTIVE: The objective of this study was to compare the clinical presentation, outcomes, complications, and diverticulum recurrence rates in women who underwent a urethral diverticulectomy with vs without a concurrent pubovaginal sling. STUDY DESIGN: This multicenter, retrospective cohort study included women who underwent a urethral diverticulectomy between January 1, 2000, and December 31, 2016. Study participants were identified by Current Procedure Terminology codes, and their records were reviewed for demographics, medical or surgical history, symptoms, preoperative testing, concomitant surgeries, and postoperative outcomes. Symptoms, recurrence rates, and complications were compared between women with and without a concomitant pubovaginal sling. The primary outcome was the presence of postoperative stress urinary incontinence symptoms. Based on a stress urinary incontinence rate of 50% with no pubovaginal sling and 10% with a pubovaginal sling, we needed a sample size of 141 participants who underwent diverticulectomy without a pubovaginal sling and 8 participants with a pubovaginal sling to achieve 83% power with P<.05. RESULTS: We identified 485 diverticulectomy cases from 11 institutions who met the inclusion criteria; of these, 96 (19.7%) cases had a concomitant pubovaginal sling. Women with a pubovaginal sling were older than those without a pubovaginal sling (53 years vs 46 years; P<.001), and a greater number of women with pubovaginal sling had undergone diverticulectomy previously (31% vs 8%; P<.001). Postoperative follow-up period (14.6±26.9 months) was similar between the groups. The pubovaginal sling group had greater preoperative stress urinary incontinence (71% vs 33%; P<.0001), dysuria (47% vs 30%; P=.002), and recurrent urinary tract infection (49% vs 33%; P=.004). The addition of a pubovaginal sling at the time of diverticulectomy significantly improved the odds of stress urinary incontinence resolution after adjusting for prior diverticulectomy, prior incontinence surgery, age, race, and parity (adjusted odds ratio, 2.27; 95% confidence interval, 1.02-5.03; P=.043). It was not significantly protective against de novo stress urinary incontinence (adjusted odds ratio, 0.86; 95% confidence interval, 0.25-2.92; P=.807). Concomitant pubovaginal sling increased the odds of postoperative short-term (<6 weeks) urinary retention (adjusted odds ratio, 2.5; 95% confidence interval, 1.04-6.22; P=.039) and long-term urinary retention (>6 weeks) (adjusted odds ratio, 6.98; 95% confidence interval, 2.20-22.11; P=.001), as well as recurrent urinary tract infections (adjusted odds ratio, 3.27; 95% confidence interval, 1.26-7.76; P=.013). There was no significant risk to develop a de novo overactive bladder (adjusted odds ratio, 1.48; 95% confidence interval, 0.56-3.91; P=.423) or urgency urinary incontinence (adjusted odds ratio, 1.47; 95% confidence interval, 0.71-3.06; P=.30). A concomitant pubovaginal sling was not protective against a recurrent diverticulum (adjusted odds ratio, 1.38; 95% confidence interval, 0.67-2.82; P=.374). Overall, the diverticulum recurrence rate was 10.1% and did not differ between the groups. CONCLUSION: This large retrospective cohort study demonstrated a greater resolution of stress urinary incontinence with the addition of a pubovaginal sling at the time of a urethral diverticulectomy. There was a considerable risk of postoperative urinary retention and recurrent urinary tract infections in the pubovaginal sling group.

Prolapse repair in the elderly patient: contemporary trends and 30-day perioperative complications.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse is common and increases with age. Although conservative options exist for management, surgery remains a mainstay of treatment. Understanding how surgical repair affects the elderly is increasingly important as the population ages. We set out to describe current treatment patterns for prolapse repair in the elderly. Our main goal was to compare perioperative morbidity and mortality for elderly patients who undergo surgical repair of pelvic organ prolapse with colpocleisis, vaginal repair or sacrocolpopexy. METHODS: Women 75 years and older who underwent prolapse repair from 2014 to 2016 were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database using Current Procedural Terminology (CPT) codes for colpocleisis, vaginal prolapse repair, and abdominal sacrocolpopexy. Variables including demographics, comorbidities, concomitant hysterectomy or stress urinary incontinence procedure, hospital length of stay, morbidity, and mortality were evaluated. A regression model was used to analyze risk factors for perioperative complications. RESULTS: We identified 764 women who underwent prolapse repair. The largest proportion of patients (334, 43.7%) underwent transvaginal repair, closely followed by colpocleisis (323, 42.3%), and the remainder (107, 14%) sacrocolpopexy. Older age and higher ASA class were significantly associated with colpocleisis (p < 0.001, p = 0.03). No difference was observed in complications across the three approaches, but length of stay was shorter (1.2 days vs 1.7 days, p = 0.03) for colpocleisis. CONCLUSIONS: In current practice, patients undergoing colpocleisis compared with transvaginal repair or sacrocolpopexy are older with more comorbidities. Despite this, length of stay remains shorter for these patients and complications rates equivalent.

Rectus Fascia Versus Fascia Lata for Autologous Fascial Pubovaginal Sling: A Single-Center Comparison of Perioperative and Functional Outcomes.

OBJECTIVE: To compare perioperative and functional outcomes of autologous fascia lata versus rectus fascia pubovaginal sling in female patients with stress urinary incontinence (SUI). METHODS: The charts of all patients undergoing pubovaginal sling for SUI from 2012 to 2017 at a single center were retrospectively reviewed. Patients were divided into 2 groups: those with the sling harvested from the fascia lata (FL group) and those with the sling harvested from the rectus fascia (RF group). RESULTS: Between 2012 and 2017, 105 women underwent pubovaginal slings: 21 using FL and 84 using RF. Operative time did not differ significantly between the FL and RF groups (84 vs 81.9 minutes; P=0.68). Estimated blood loss was lower in the FL group (91.7 vs 141.6 mL; P=0.04). There were more wound complications in the RF group, although this was not statistically significant (0% vs 14.3%; P=0.12). Overall complications were comparable between FL and RF groups (52.4% vs 48.9%; P=0.81), but the proportion of Clavien grade 2 or greater were higher in the RF group (4.8% vs 20.2%; P=0.11). Overall, wound complications accounted for 29.3% of postoperative complications in the RF group (12/41). Functional outcomes were comparable between FL and RF groups, with similar rates of patients without SUI symptoms after 1 month (82.4% vs 76.4%; P=0.74), 1 year (55.6% vs 63.8%; P=0.76), and at the latest follow-up (66.7% vs 65.8%; P=0.87). CONCLUSIONS: When compared with rectus fascia for pubovaginal sling, fascia lata may decrease perioperative morbidity, especially wound complications, without compromising functional outcomes.

Non-adherence to labor guidelines in cesarean sections done for failed induction and arrest of dilation.

OBJECTIVES: In 2014, the American College of Obstetrics and Gynecology published guidelines for diagnosing failed induction of labor (FIOL) and arrest of dilation (AOD) to prevent cesarean delivery (CD). The objectives of this study were to determine the rate of adherence to these guidelines and to compare the association of guideline adherence with physician CD rates and obstetric/neonatal outcomes. METHODS: Retrospective cohort review of singleton primary cesarean deliveries for FIOL and AOD at a single academic institution from 2014 to 2016. Univariate and multivariate analyses were used to compare adherence to the guidelines with physician CD rates and obstetric/neonatal outcomes. RESULTS: Of the 591 cesarean deliveries in the study, 263 were for failed induction, 328 for AOD and 79% (468/591) were not adherent to the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (ACOG/SMFM) guidelines. Of the failed inductions, 82% (215/263) and of the AODs 77% (253/328) were not adherent. There was no difference between adherent and non-adherent CDs with regard to maternal characteristics, or obstetric/neonatal outcomes. Duration of oxytocin use after rupture of membranes, dilation at time of CD, and birth weight were statistically higher in adherent CDs. On multivariate linear regression, physician CD rates were inversely correlated with adherence to ACOG/SMFM guidelines (p<0.0001), gestational age (p=0.007), and parity (p=0.003). CONCLUSIONS: Our study shows that physician non-compliance with ACOG guidelines was high. Adherence to these guidelines was associated with lower physician CD rates, without an increase in obstetric or neonatal complications.

Trends in Stress Urinary Incontinence Surgery at a Tertiary Center: Midurethral Sling Use Following the AUGS/SUFU Position Statement.

OBJECTIVE: To investigate trends in stress urinary incontinence (SUI) surgery before and after the 2011 Foods and Drug Administration notification and the 2014 (American Urogynecologic Society [AUGS]/Society for Urodynamics Female Pelvic Medicine and Urogenital Reconstruction [SUFU]) position statement. METHODS: A retrospective chart review was performed to identify patients presenting for evaluation of SUI by 2 Female Pelvic Medicine and Reconstructive Surgery specialists between June 1, 2010 and May 31, 2017. Rates of surgical treatment modality (synthetic midurethral slings [MUS] versus autologous fascial pubovaginal sling versus bulking agents) were analyzed at 6-month intervals. RESULTS: Over fourteen 6-month intervals, the number of new patients presenting for evaluation of SUI increased consistently. There was a decrease in the proportion of new patients who underwent antiincontinence surgical procedures, specifically MUS, between December 2011 and December 2013. After the integration of the 2014 AUGS/SUFU position statement in patient counseling, this trend reverted and we noted a sustained increase in the proportion of patients electing surgical management. This paralleled an increase in new patient visits for SUI and MUS. The number autologous fascial pubovaginal sling remained stable throughout the study period. Conversely, MUS composed the highest proportion of procedures performed, accounting for 60 %-87.2% off all antiincontinence procedures. CONCLUSION: After the Foods and Drug Administration Public Health Notification in 2011, we observed a decline in the number of new patients presenting with SUI electing surgical management, specifically MUS. However, after the AUGS/SUFU position statement publication and integration into counseling, we observed a reversal in the previous year's trends, noting a resurgence of MUS utilization.

Delivery of intercellular adhesion molecule-1 antisense oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy/ischemia model.

OBJECTIVES: Ischemia/reperfusion injury is a leading cause of renal damage which can be improved with antisense oligonucleotide gene therapy. We have shown that polyethylene glycol (PEG) hydrogel, which also functions as a tissue sealant, is an effective topical delivery vehicle for oligonucleotides in a murine partial nephrectomy model. The objective of this study was to use and evaluate this method against intercellular adhesion molecule-1 (ICAM-1) to prevent tissue damage. METHODS: Sixty mice underwent left upper pole partial nephrectomy with 45 minutes of warm ischemia, randomized to treatment with 50 microg ICAM-1 antisense oligonucleotides embedded in PEG hydrogel, no therapy, or sham surgery. Kidneys were harvested at 24 hours and 3, 4, and 5 days. The specimens were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) for ICAM-1 messenger ribonucleic acid (mRNA), immunohistochemical staining for ICAM-1 protein, and standard histology. RESULTS: At 24 hours, qRT-PCR and immunohistochemistry data showed a significant reduction in ICAM-1 mRNA and protein expression in the antisense group versus the ischemia group, but no difference at 3 to 5 days. Histologically there was reduced inflammation and necrosis in the cortex at 24 hours. The outer and inner medulla also showed improvement at 3 to 5 days in the antisense group as opposed to the ischemia group. CONCLUSIONS: Topical PEG hydrogel delivery of antisense ICAM-1 oligonucleotides demonstrated decreased ICAM-1 mRNA expression, reduced ICAM-1 protein staining, and decreased cellular damage. The application of gene therapy through this novel topical delivery system holds potential for a highly specific, localized method of preventing tissue damage after ischemia/reperfusion injury.

The role of angiotensin II in stress urinary incontinence: A rat model.

AIMS: Pharmacological treatment for stress urinary incontinence (SUI) is limited to the use of non-selective alpha-agonists, which are often ineffective. Non-adrenergic mechanisms have also been implicated in urethral closure, including angiotensin II (Ang-II), which has been demonstrated throughout the urinary tract. We investigate the role of Ang-II in urethral tone in a rat model of SUI. METHODS: Abdominal leak point pressure (ALPP) and retrograde urethral pressure profilometry (RLPP) were measured in 70 female virgin rats. Thirty rats underwent pudendal nerve injury (PNT), 30 had circumferential urethrolysis (U-Lys), and 10 had sham surgery. Rats received daily doses of Angiotensin Type 1 (AT-1) receptor inhibitor (20 mg/kg), Angiotensin Type 2 (AT-2) receptor antagonist (10 mg/kg), or Ang-II (2 mg/kg). RESULTS: Following U-Lys, RLPP and ALPP decreased from 21.4 +/- 2.0 and 39.2 +/- 3.3 mm Hg, to 13.1 +/- 1.5 and 21.6 +/- 1.9 mmHg, respectively (P < 0.01). After PNT, RLPP, and ALPP decreased from 21.0 +/- 1.6 and 41.9 +/- 3.0 mmHg to 13.1 +/- 1.5 and 24.7 +/- 3.3 mmHg, respectively (P < 0.01). AT-1 inhibitor caused significant decrease in RLPP and ALPP from 21.0 +/- 6.2 and 41.8 +/- 9.4 mmHg, to 12.0 +/- 3.8 and 25.6 +/- 6.6 mmHg, respectively (P < 0.01). Likewise, AT-2 treatment reduced RLPP and ALPP from 21.4 +/- 6.3 and 40.1 +/- 1.7 mmHg, to 13.5 +/- 5.7 and 31.0 +/- 7.2 mmHg, respectively (P < 0.01). Following surgery, Ang-II administration restored RLPP and ALPP to baseline presurgical values. CONCLUSIONS: AT-1 and AT-2 receptor inhibition significantly lowers urethral resistance, comparable to either neurogenic or urethrolytic injury. Ang-II treatment restored urethral tone in rats with intrinsic sphincter dysfunction. Ang II appears to serve a functional role in the maintenance of urethral tone and stress continence.