Transforming growth factor beta1 gene expression during vaginal wound healing in a rabbit menopause model.

OBJECTIVE: Surgical outcome following reconstructive pelvic surgery is largely dependent on the vaginal wound healing process. As peri- and post-menopausal women are the most likely candidates to undergo these surgeries, it is important to understand the effect of estrogen deficiency on this process. Transforming growth factor beta (TGFß) is an important mediator of wound healing. We sought to assess TGFß1 gene expression during the vaginal incisional wound healing process in a rabbit menopause model. DESIGN: Animal study. SETTING: Animal laboratory. SAMPLE: Sixty-three rabbits were used for this study. METHODS: Twenty-one underwent bilateral oophorectomy, 21 underwent a sham surgery, and 21 served as controls. Eight weeks later, standardised full-thickness 6-mm diameter circular segments were excised from the vagina of all rabbits. Animals were killed sequentially, before wounding, and at 0, 4, 7, 14, 21 and 35 days after wounding, and the wounds were harvested. MAIN OUTCOME MEASURES: Wound closure and TGFß1 gene transcription, as measured by real-time polymerase chain reaction (PCR). RESULTS: Wound closure was significantly protracted (P < 0.02), whereas TGFß1 gene expression was significantly increased (P < 0.0001) during the wound healing process in oophorectomised rabbits, as compared with both control and sham groups. CONCLUSION: Oophorectomised rabbits show protracted incisional vaginal wound healing associated with increased TGFß1 gene transcription.

Trospium chloride once-daily extended release is effective and well tolerated for the treatment of overactive bladder syndrome: an integrated analysis of two randomised, phase III trials.

BACKGROUND: Trospium chloride is an antimuscarinic agent with a hydrophilic polar quaternary amine structure that is minimally metabolised by hepatic cytochrome P450 and is actively excreted in the urine, each of which confers a potential benefit with regard to efficacy and tolerability. PURPOSE: We analysed pooled data from two identically designed phase III trials of a once-daily, extended-release (XR) formulation of trospium chloride (trospium XR 60-mg capsules) in subjects with overactive bladder syndrome (OAB). METHODS: Adults with OAB of > or = 6 months' duration with urinary urgency, frequency and > or = 1 urge urinary incontinence (UUI) episode/day were enrolled in these multicentre, parallel-group, double-blind trials. Participants were randomised (1 : 1) to receive trospium XR 60 mg or placebo for 12 weeks. Primary efficacy variables were changes in urinary frequency and the number of UUI episodes/day. Adverse events (AEs) were recorded throughout. RESULTS: In total, 1165 subjects were randomised (trospium XR, 578; placebo, 587). At baseline, subjects averaged 12.8 toilet voids/day and 4.1 UUI episodes/day. Compared with placebo, subjects treated with trospium XR had significantly greater reductions from baseline in the mean number of toilet voids/day (-1.9 vs. -2.7; p < 0.001) and UUI episodes/day (-1.8 vs. -2.4; p < 0.001) at week 12. The most frequent AEs considered possibly related to study treatment were dry mouth (trospium XR, 10.7%; placebo, 3.7%) and constipation (trospium XR, 8.5%; placebo, 1.5%). Notably, rates of central nervous system (CNS) AEs were lower with trospium XR vs. placebo (dizziness: 0.2% vs. 1.0%; headache: 1.4% vs. 2.4%). CONCLUSIONS: Treatment with trospium XR resulted in statistically significant improvements in both of the dual primary and all of the secondary outcome variables. Trospium XR demonstrated favourable rates of AEs, particularly CNS AEs (numerically lower than with placebo) and dry mouth (lower than previously reported with trospium immediate-release, although not compared in a head-to-head study).

Evaluation and treatment of female urinary incontinence.

Urinary incontinence is a very common and bothersome condition among women and can affect up to 50% of women during their lifetime. Older women are disproportionately affected and often view urinary incontinence as a normal part of aging thus precluding contact with medical professionals. Physicians must, therefore, include questions regarding urinary incontinence as part of routine examinations. A simple, yet thorough history and physical examination along with basic testing can often aid the physician in making an accurate diagnosis and initiating effective treatment. Several interventions are available and are often chosen based on type and severity of urinary incontinence. These include conservative measures, pharmacotherapy, and surgical intervention. Also, innovative treatment modalities are constantly being investigated to manage urinary incontinence further expanding treatment options available to women.

Evaluation and treatment of female urinary incontinence.

Urinary incontinence is a very common and bothersome condition among women and can affect up to 50% of women during their lifetime. Older women are disproportionately affected and often view urinary incontinence as a normal part of aging, thus precluding contact with medical professionals. Physicians must therefore include questions regarding urinary incontinence as part of routing examinations. A simple, yet thorough history and physical examination along with basic testing can often aid the physician in making an accurate diagnosis and initiating effective treatment. Several interventions are available and are often chosen based on type and severity of urinary incontinence. These include conservative measures, pharmacotherapy, and surgical intervention. Also, innovative treatment modalities are constantly being investigated to manage urinary incontinence further expanding treatment options available to women.

Diagnosis and treatment of overactive bladder.

Overactive bladder is a very common condition, affecting an estimated 50 to 100 million people worldwide. More than 90% of women with overactive bladder have no recognizable pathology. Several risk factors have been recognized for overactive bladder syndrome and incontinence including age, diabetes, Caucasian race, and hormone replacement therapy. The gold standard for diagnosing detrusor overactivity is multichannel urethrocystometry, although single channel cystometry or even simple cystometry may be used. A variety of interventions are available for the treatment of the overactive bladder syndrome. These include behavioral interventions, pelvic floor electrical stimulation, electromagnetic innervation, neuromodulation, intravesical instillations and injections, operative bladder augmentation, and pharmacotherapy. In any therapy for overactive bladder symptoms, expectations play a pivotal role in success or failure, and communication between the healthcare provider and the patient is essential for setting and achieving treatment goals.

Pelvic floor stimulation in the treatment of mixed incontinence complicated by a low-pressure urethra.

OBJECTIVE: To determine the efficacy and safety of transvaginal pelvic floor stimulation in the treatment of women with genuine stress incontinence and detrusor instability complicated by a low-pressure urethra. METHODS: Twenty-six consecutive women with mixed incontinence complicated by a low-pressure urethra who elected to try pelvic floor stimulation were studied. Visual analogue symptom scales and weekly incontinence episodes were compared before and after 8 weeks of twice-daily device use. RESULTS: The symptoms of stress and urge incontinence were completely resolved in six (23%) and ten (38%) women, respectively. Ten of 26 subjects (38%) had greater than 50% overall symptomatic improvement, and two subjects (8%) were completely dry during their last week of therapy. Symptoms of urinary frequency, urgency, and stress incontinence improved significantly. No factors were found to be predictive of treatment success. CONCLUSION: Pelvic floor stimulation was found to be an effective and safe treatment for some patients with genuine stress incontinence and detrusor instability complicated by a low-pressure urethra.

Incisional hernia after suprapubic catheterization.

BACKGROUND: Suprapubic catheterization is a popular method of bladder drainage after gynecologic surgery. We report two cases of incisional hernia that developed after suprapubic catheterization. CASES: The first case involved a 64-year-old woman who underwent Burch urethropexy. Her suprapubic catheter was not removed until postoperative day 55 because of prolonged retention. She presented 1 month later with abdominal pain. In the second case, a 65-year-old woman had vesicovaginal fistula repair with suprapubic catheterization for 2 weeks after surgery. Five months later, she presented with abdominal pain. In both cases, examination revealed a hernia at the catheter exit site. CONCLUSION: Incisional hernia is a rare complication of suprapubic catheterization that should be considered in patients who present with abdominal discomfort some time after catheterization.

The empty supine stress test as a predictor of intrinsic urethral sphincter dysfunction.

OBJECTIVE: To assess the usefulness of a proposed test for intrinsic urethral sphincter dysfunction. METHODS: Subjects were included in the study if they had complaints of incontinence, did not have substantial pelvic prolapse, and had undergone multichannel urodynamic testing. The initial evaluation involved uroflowmetry, catheterized residual urine, history, urogenital examination, and a cough stress test within 20 minutes after catheterization. Standardized multichannel urodynamic testing was performed at a follow-up appointment. Test indices were calculated based on the result of the empty supine stress test, the presence of genuine stress incontinence, and maximum urethral closure pressures. RESULTS: Three hundred four women met the inclusion criteria; 124 had a positive empty supine stress test and 180 had a negative test. Genuine stress incontinence was diagnosed in 238 subjects. A positive empty supine stress test was found to have 70% sensitivity and 90% negative predictive value for detecting very low urethral closure pressures, and 98% positive predictive value for genuine stress incontinence; in low-risk populations, the test had 95% negative predictive value for excluding urethral dysfunction. CONCLUSION: The empty supine stress test is easy to perform, inexpensive, and without significant risk. By itself, a positive empty supine stress test is essentially diagnostic for genuine stress incontinence, and in combination with a fixed urethra, it is diagnostic for intrinsic urethral sphincter dysfunction. In low-prevalence populations, a negative test reliably excludes the presence of intrinsic urethral sphincter dysfunction. However, for high-prevalence and referral populations, the low predictive values of the test limit its usefulness.

Simple standing incremental cystometry as a screening method for detrusor instability.

One hundred consecutive neurologically normal women complaining of urinary incontinence underwent standing incremental retrograde medium-fill water cystometrograms on two different days followed by sitting and standing continuous retrograde medium-fill water urethrocystometry on a third visit between November 1987 and February 1989. Studies were done to assess the reproducibility, sensitivity, specificity, and predictive values of a simple cystometer. Standing incremental, retrograde cystometry was found to be relatively inexpensive, simple, reproducible, and sensitive. The two cystometrograms yielded similar results in 84% of the patients. The sensitivities were found to be 84.3 and 90.2% for the first and second cystometrograms, respectively. Using both cystometrograms together, we were able to detect detrusor instability with a sensitivity of 92.3% and to predict its absence with a negative predictive value of 86.7%. Detrusor instability was found in 64% of these patients. Based on these results, it was concluded that when multichannel urodynamics are not available in a high-prevalence population, standing retrograde incremental water cystometry done on two occasions may offer the physician an accurate alternative for the diagnosis of detrusor instability.

The low pressure urethra as a factor in failed retropubic urethropexy.

Eighty-six patients with preoperative and postoperative urodynamic studies who underwent modified Burch colposuspensions were divided into two groups, one with a urethral closure pressure of 20 cm H2O or lower, and one with a pressure over 20 cm H2O. The two groups were comparable except for a difference in age (53.3 versus 46.6 years; P less than .01). There were significant differences between the two groups in both preoperative and postoperative functional lengths and closure pressures (P less than .01). The low-urethral-pressure group had a 54% failure rate, compared with 18% in the group with urethral closure pressures above 20 cm H2O (P less than .0005). Low urethral pressure was found to be a significant independent risk factor for patients under the age of 50, but not independent of age in women over 50 years old. Patients under the age of 50 who have urethral closure pressures of 20 cm H2O or lower are at high risk of surgical failure when undergoing a modified Burch colposuspension (P less than .0002). These patients should not be considered appropriate candidates for this procedure.

Supine urethroscopic and standing cystometry as screening methods for the detection of detrusor instability.

Two hundred eighteen women undergoing multichannel urethrocystometry were also studied with supine urethroscopic cystometry and/or standing single-channel cystometry to evaluate the use of the latter two studies in screening patients at risk for detrusor instability. Thirty-one percent of the women were found to have detrusor instability on multichannel urethrocystometry. Only 24.6% of these patients were detected with supine urethroscopic cystometry, whereas 59.3% were detected with standing single-channel cystometry. The specificity of these tests was better (94.4 and 82.4%, respectively) than the above sensitivities, but analysis of their predictive values confirmed that they are both poor screening tools for populations at risk for detrusor instability.

Incontinence history as a predictor of detrusor stability.

Between January 1983 and July 1985, 218 women underwent preliminary evaluation and urodynamic testing in our laboratory. Their symptoms and urodynamic diagnoses were compared to evaluate the ability of a patient's history to predict the stability of the detrusor. The symptom of stress incontinence was a sensitive detector of genuine stress incontinence (100% sensitivity) but was not very specific (65.2%). The symptoms of urgency and urge incontinence were found to have limited sensitivity (77.9%) and specificity (38.7%) in the detection of detrusor instability. Even patients with isolated complaints of stress incontinence had an incidence of detrusor instability of 34.9%, whereas 76.9% of those with a history of isolated urgency and urge incontinence had detrusor instability. Three percent of patients complaining of either type of incontinence had no objective evidence of incontinence on urodynamic investigation. The results of this study demonstrate that a patient's history is a poor predictor of the underlying cause of incontinence.

Repeat gestational trophoblastic disease.

During a ten-year period from 1969 through 1979, 22 of 1648 patients referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School had repeat gestational trophoblastic disease, an incidence of 1.33%. A total of 52 trophoblastic disease episodes occurred in these 22 patients. Invasive mole or choriocarcinoma occurred as the first trophoblastic disease episode in only three patients (14%), whereas one of these sequelae was the second trophoblastic disease event in seven patients (32%). Seventeen patients (77%) had consecutive trophoblastic disease episodes. After a second trophoblastic disease episode, the risk for a subsequent event rose to 28%; however, 44% of these patients delivered viable infants. There was no difference in outcome of subsequent pregnancies with respect to previous chemotherapy.

Choriocarcinoma associated with ectopic pregnancy.

Eight patients with choriocarcinoma associated with ectopic pregnancy were treated at the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School from 1962 through 1981. This represented 4% of the 197 patients with documented choriocarcinoma or 1.7% of all 459 patients with gestational trophoblastic disease treated with chemotherapy at the center during this 20-year period. The presenting signs and symptoms were similar to those classically outlined for ectopic pregnancies: amenorrhea and abdominal pain (88%), irregular vaginal bleeding (75%), positive pregnancy test (100%), and adnexal mass (50%). Six patients (75%) had metastatic disease and four of these six had one or more high-risk factors. Two patients (25%) died of metastatic disease, both of whom had received chemotherapy elsewhere before referral to the center.

Uninhibited urethral relaxation: an unusual cause of incontinence.

Uninhibited urethral relaxation appears to be a clinically distinct cause of urinary incontinence. It was found in 11 of 534 incontinent women who had multichannel urodynamic evaluation, and in 2 of these it was the sole cause of incontinence. This diagnosis should only be made after careful scrutiny has ruled out a low pressure detrusor contraction, cough, valsalva, or heel bounce as the cause of the urethral relaxation. Because the majority of patients had a voiding mechanism that included a detrusor contraction, it is unlikely that uninhibited urethral relaxation represents a variant of detrusor instability in patients unable to generate a detrusor contraction. It most likely reflects an exaggeration of urethral instability due to relaxation of the smooth and/or striated urethral musculature.

The effect of retropubic urethropexy on detrusor stability.

A group of 86 women with genuine stress incontinence who underwent retropubic urethropexy were evaluated with both pre- and postoperative urodynamics. Twenty of these 86 women (23.3%) also had unstable detrusors preoperatively. Eleven of these 20 women (55%) had stable detrusors after retropubic urethropexy. Five of the 66 patients (7.6%) who had stable detrusors preoperatively were found to have unstable detrusors on postoperative urethrocystometry. The overall cure rate for women with detrusor instability and genuine stress incontinence was only 30%. Analysis of symptoms, previous anti-incontinence procedures, age, parity, and cystometric parameters revealed no differences between those women who had stable detrusors after retropubic urethropexy and those who remained unstable. Similarly, patients whose bladders became unstable after retropubic urethropexy could not be distinguished from those who remained stable. Patients undergoing retropubic urethropexy should understand the possibility that the operation may cause urinary incontinence due to detrusor instability even if it cures their genuine stress incontinence, and that if they have both genuine stress incontinence and detrusor instability, their chances for an operative cure of both conditions are low.

Evaluation of male consorts of women with genital human papilloma virus infection.

Ninety male partners of women with genital condylomata were evaluated for evidence of condylomata by visual examination of the genitalia with the colposcope, urethroscopy, and biopsy. Fifty-three men (59%) were found initially to have condylomata and nine other cases were found on reevaluation for a total prevalence of 69%. Thorough evaluation with the use of acetic acid, magnification and liberal use of biopsy is stressed. Urethroscopy may not be a necessary part of the routine screening evaluation.

Comparison of microtransducer and fiberoptic catheters for urodynamic studies.

OBJECTIVE: To assess the validity and reproducibility of a fiberoptic transducer urodynamic catheter for urethral closure pressure profiles and leak point pressure determination, using a microtransducer catheter as the standard. METHODS: Ninety women without significant pelvic organ prolapse underwent urodynamic evaluations with both fiberoptic and microtransducer catheters. Maximal urethral closure pressures and "leak point pressures" were repeatedly measured by the two catheters and statistically compared. The order of catheter use was randomized. RESULTS: Significantly lower mean maximal urethral closure pressures were recorded by the fiberoptic system than by the microtransducer system (28.9 cmH(2)O +/- 17.3 versus 43.2 cmH(2)O +/- 24.9, P <.001). The fiberoptic catheter predicted microtransducer values for maximum urethral closure pressure only within a range of 27 cmH(2)O. Mean "leak point pressure" recorded by the fiberoptic catheters (66.9 cmH(2)O +/- 2.9) was not significantly different than that recorded by the microtransducer catheters (66.4 cmH(2)O +/- 2.9, P =.97). CONCLUSION: There is a significant difference between maximum urethral closure pressure values recorded by the microtransducer and fiberoptic catheter systems. No significant difference was found between the two systems in measurement of Valsalva "leak point pressure."

Anterior or posterior sacrospinous vaginal vault suspension: long-term anatomic and functional evaluation.

OBJECTIVE: To compare vaginal anatomy and sexual function after the conventional posterior and anterior sacrospinous vault suspension. METHODS: A retrospective repeated measures cohort study included all 168 consecutive sacrospinous vault suspension procedures between July 1990 and February 1997. The posterior suspension (n = 92) used a posterior vaginal incision and pararectal dissection. Anterior suspension (n = 76) involved an anterior rather than posterior vaginal incision, retropubic perforation, and dissection of a paravaginal-paravesical rather than pararectal space to accommodate the vaginal vault. Two polytetrafluoroethylene (00) sutures anchored the anterior vaginal cuff (for the anterior sacrospinous suspension) or the posterior vaginal cuff (for the posterior sacrospinous suspension) to the ligament. Postoperative evaluation included an examination using the pelvic organ prolapse quantitative system, assessment of vaginal width and axis, and symptom questionnaire. RESULTS: Total vaginal length and apical suspension were slightly greater after the anterior suspension, and recurrent anterior vaginal relaxation was less likely. No differences were found in maximal dilator size or apical narrowing between the two groups. New onset dyspareunia was reported by two subjects in the anterior vault suspension group, and two in the posterior vault suspension group. Three of these four cases of de novo dyspareunia were attributable to either severe atrophy or recurrent prolapse, and none to vaginal narrowing or shortening. CONCLUSION: After anterior sacrospinous vault suspension, vaginal length and apical suspension were slightly increased, and recurrent anterior vaginal prolapse decreased compared with the posterior sacrospinous suspension technique. Upper vaginal caliber and sexual function appear well preserved using either technique.

Pelvic floor electrical stimulation for the treatment of urge and mixed urinary incontinence in women.

OBJECTIVES: To determine the efficacy of daily or every-other-day electrical stimulation in treating detrusor instability (urge) or urge plus genuine stress (mixed) urinary incontinence in women. METHODS: A multicenter, prospective, nonrandomized study enrolled subjects with urge and mixed urinary incontinence assigned to daily or every-other-day treatments (15 minutes twice daily) using pelvic floor stimulation. Outcome measures assessed were (1) leakage episodes, nocturnal episodes, voiding frequency, total voids, and pad count, and (2) patient subjective assessment and quality of life. RESULTS: Seventy-two subjects were enrolled. Sixty-eight subjects completed the 20-week protocol: 33 treated daily and 35 treated every other day. The entire study group (n = 68) experienced a significant decrease in total leaks (P < 0.001), nocturnal episodes (P = 0.001), pad count (P = 0.002), and total voids (P = 0.003) and on visual analog scales. Sixty-nine percent (n = 46) of subjects with urge or mixed incontinence were cured or improved by at least 50%, with 28% (n = 19) being cured. There were no significant differences between daily and every-other-day users. Nonresponse was correlated with number of previous therapies (P < 0.001) and number of vaginal deliveries (P = 0.007). Overall, subjects were 93% compliant with device use, and 72% (n = 47) were satisfied with the therapy. CONCLUSIONS: Twenty weeks of pelvic floor electrical stimulation therapy is effective in treating urge and mixed urinary incontinence, regardless of daily or every-other-day treatments.