Epigenetic reprogramming governs EcSOD expression during human mammary epithelial cell differentiation, tumorigenesis and metastasis.

Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that the 2D-cultured condition induces a repressive status of EcSOD gene expression in HMEC. With the use of laminin-enriched extracellular matrix (lrECM), we were able to detect expression of EcSOD when HMEC formed polarized acinar structures in a 3D-culture condition. Repression of the EcSOD-gene expression was again seen when the HMEC acini were sub-cultured as a monolayer, implying that lrECM-induced acinar morphogenesis is essential in EcSOD-gene activation. We have further shown the involvement of DNA methylation in regulating EcSOD expression in HMEC under these cell culture conditions. EcSOD mRNA expression was strongly induced in the 2D-cultured HMEC after treatment with a DNA methyltransferase inhibitor. In addition, epigenetic analyses showed a decrease in the degree of CpG methylation in the EcSOD promoter in the 3D versus 2D-cultured HMEC. More importantly, >80% of clinical mammary adenocarcinoma samples showed significantly decreased EcSOD mRNA and protein expression levels compared with normal mammary tissues and there is an inverse correlation between the expression levels of EcSOD and the clinical stages of breast cancer. Combined bisulfite restriction analysis analysis of some of the tumors also revealed an association of DNA methylation with the loss of EcSOD expression in vivo. Furthermore, overexpression of EcSOD inhibited breast cancer metastasis in both the experimental lung metastasis model and the syngeneic mouse model. This study suggests that epigenetic silencing of EcSOD may contribute to mammary tumorigenesis and that restoring the extracellular superoxide scavenging activity could be an effective strategy for breast cancer treatment.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Pelvic support, pelvic symptoms, and patient satisfaction after colpocleisis.

The objective was to study the effect of colpocleisis on pelvic support, symptoms, and quality of life and report-associated morbidity and postoperative satisfaction. Women undergoing colpocleisis for treatment of pelvic organ prolapse (POP) were recruited at six centers. Baseline measures included physical examination, responses to the Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire. Three and 12 months after surgery we repeated baseline measures. Of 152 patients with mean age 79 (+/-6) years, 132 (87%) completed 1 year follow-up. Three and 12 months after surgery, 90/110 (82%) and 75/103 (73%) patients following up had POP stage < or = 1. All pelvic symptom scores and related bother significantly improved at 3 and 12 months, and 125 (95%) patients said they were either 'very satisfied' or 'satisfied' with the outcome of their surgery. Colpocleisis was effective in resolving prolapse and pelvic symptoms and was associated with high patient satisfaction.

Prolapse severity, symptoms and impact on quality of life among women planning sacrocolpopexy.

OBJECTIVES: To explore the relationship between severity of pelvic organ prolapse (POP), symptoms of pelvic dysfunction and quality of life using validated measures. METHOD: Baseline data from 314 participants in the Colpopexy And Urinary Reduction Efforts (CARE) trial were analyzed. Pelvic symptoms and impact were assessed using the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ). PFDI and PFIQ scores were compared by prolapse stage and history of incontinence or POP surgery. Regression analyses were performed to identify other predictors of symptoms and impact. RESULTS: Women were predominantly (90%) Caucasian and had mean age of 61 years. Women with stage II POP, especially those with prior surgery, reported more symptoms and impact than women with more advanced POP. There were no other significant predictors of symptoms or life impact. CONCLUSIONS: Women planning sacrocolpopexy with stage II prolapse and prior pelvic surgery reported more symptoms and quality of life impact than those with more advanced prolapse.

Reference urodynamic values for stress incontinent women.

OBJECTIVE: To determine reference urodynamic values for preoperative urodynamic studies in women undergoing surgery for pure or predominant stress urinary incontinence (SUI). MATERIALS AND METHODS: Six hundred fifty-five women with pure or predominant SUI were enrolled in a multicenter surgical trial and were randomized to undergo a Burch or autologous fascia sling procedure as part of the Urinary Incontinence Treatment Network (UITN) Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr). Preoperative free uroflowmetry, filling cystometry, and pressure flow studies were performed in all women using a standardized research protocol and standardized urodynamic interpretation guidelines. We define the normal range of urodynamic values in this population as the values that encompass 95% of the results. RESULTS: In 655 women undergoing filling cystometry in the standing position, baseline vesical and abdominal pressures were between 12 and 60 cm H(2)O. The upper limit of detrusor pressure increase during bladder filling to maximum cystometric capacity was 16 cm H(2)O. Ten percent of women who qualified for stress incontinence surgery with a positive cough stress test on physical exam did not demonstrate urodynamic stress incontinence (USI) and less than 10% of subjects in this study demonstrated detrusor overactivity. CONCLUSIONS: Results from a large cohort of women with SUI are now available for quantitative plausibility assessments or as reference values when interpreting urodynamic studies.

Urodynamic prolapse reduction alters urethral pressure but not filling or pressure flow parameters.

PURPOSE: To test the hypothesis that advanced stages of pelvic organ prolapse can result in a functional obstruction of the urethra, we studied the effects of manual prolapse reduction on urodynamic and urethral electromyographic parameters in women with stage III and IV pelvic organ prolapse. MATERIALS AND METHODS: Women with advanced pelvic organ prolapse undergoing clinical multichannel urodynamics with concentric needle electromyography of the urethra were invited to participate in this institutional review board approved study. Women underwent filling cystometry and electromyography with prolapse everted and with prolapse reduced. Women were randomized to cystometry order (reduced vs everted). All subjects underwent a third study with prolapse reduction. Maximum urethral closure pressure and quantitative electromyography of the striated urethral sphincter were determined at maximum cystometric capacity. During the pressure flow study voiding parameters, including urethral electromyography quieting, were determined. The nonparametric paired sign test was used to evaluate differences in urodynamic parameters and quantitative electromyography with pelvic organ prolapse reduced and unreduced. Results were considered significant at the 5% level. RESULTS: The 31 participants had mean age of 60 years (range 36 to 78) and 83% were white. There were no clinically significant differences in maximum cystometric capacity, voided volume, maximal flow and detrusor pressure at maximal flow or time to maximal flow between the reduced and everted prolapse states. Prolapse reduction resulted in a clinically and statistically significant decrease in maximum urethral closure pressure (-31%) but it had no impact on quantitative urethral electromyography. CONCLUSIONS: These findings demonstrate that, although prolapse reduction significantly decreases maximum urethral closure pressure, it does not alter intrinsic neuromuscular activity of the striated urethral sphincter. Prolapse reduction does not alter any other filling or pressure flow parameter.

Interrater reliability of filling cystometrogram interpretation in a multicenter study.

PURPOSE: As part of a continuous quality control effort to measure the interrater reliability of urodynamic studies performed at multiple centers, we compared agreement levels for urodynamic studies between central and local physician reviewers. We report interrater reliability findings for the filling cystometrogram. MATERIALS AND METHODS: Following a satisfactory interrater reliability study among 4 central physician reviewers in 33 tracings 36 urodynamic study tracings from 9 Urinary Incontinence Treatment Network continence treatment centers and 13 Urinary Incontinence Treatment Network certified urodynamic study testers were randomly selected for review. These tracings were originally interpreted by 11 local physician reviewers using standardized Urinary Incontinence Treatment Network interpretation guidelines. Each of the 4 central physician reviewers reviewed 9 randomly assigned tracings and none reviewed tracings from his or her center. Local and central physician reviewers were instructed to categorize values as invalid if specified technical quality assurance standards were not met or the signal pattern suggested implausible values because of technical deficiencies. An intraclass correlation coefficient was calculated for continuous (numerical) variables and a kappa statistic was calculated for qualitative values with acceptable agreement defined a priori as an intraclass correlation coefficient of greater than 0.6. RESULTS: Filling cystometrogram baseline pressure, Valsalva leak point pressure, and volume and pressure measurements at maximum cystometric capacity had excellent intraclass correlation coefficients of 0.74 to 0.99. There were no significant differences between local and central physician reviewer means, indicating excellent agreement. CONCLUSIONS: With proper quality control measures in place and a set of standardized interpretive guidelines excellent interrater reliability between local and central physician reviewer can be achieved for numerical cystometrogram variables.

What is the pain of interstitial cystitis like?

To describe the characteristics of pain experienced by patients with interstitial cystitis (IC) in terms of pain site, severity, and character, we performed a secondary analysis of data from the IC database (ICDB), which was a prospective, longitudinal, cohort study of IC patients. We analyzed the cross-sectional baseline data from 629 patients who had a completed baseline symptom questionnaire. Patients answered questions about whether they had pain or discomfort associated with urinary symptoms over the past 4 weeks and if so, about the location, characteristics, intensity, and frequency of their pain. Logistic regression examined associations between pain location and the presence of urinary symptoms. Analyses were performed using SAS version 8.2 (SAS Institute, Cary, NC, USA) and considered significant at the 5% level. Five hundred and eighty-nine (94%) patients with a mean age of 45 years (SD 14 years) reported baseline pain or discomfort associated with their urinary symptoms. The most common baseline pain site was lower abdominal (80%), with urethral (74%) and low back pain (65%) also commonly reported. The majority of patients described their pain as intermittent, regardless of the pain site. Most patients reported moderate pain intensity, across all pain sites. There was a statistically significant link between pain in the urethra, lower back, and lower abdomen, and urinary symptoms. Patients with IC report pain at several sites other than the bladder, possibly arising from the previously well-described myofascial abnormalities of pelvic floor and abdominal wall present in patients with IC and other chronic pelvic pain syndromes.

Responsiveness of quality of life measurements to change after reconstructive pelvic surgery.

OBJECTIVE: We sought to determine whether Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores are sensitive to changes in clinical status after surgery for genuine stress incontinence (GSI) or pelvic organ prolapse (POP). STUDY DESIGN: Patients were included in this study if they had completed the IIQ-7 and UDI-6 scales and had undergone urodynamic testing before and 3 months after surgery for GSI or POP. Kruskal-Wallis tests and logistic regression were used to compare IIQ-7 and UDI-6 scores according to the outcome of surgery. RESULTS: Among 55 patients satisfying inclusion criteria for the study, 34 (62%) underwent Burch colposuspension, and 21 (38%) underwent suburethral sling procedures for GSI; 44 (80%) patients were subjectively continent after surgery. Thirty-four (62%) patients underwent surgical treatment of their POP; 31 (90%) were subjectively cured of their POP symptoms. Mean IIQ-7 and UDI-6 scores were lower in patients who were subjectively continent, and UDI-6 scores were lower in patients who were objectively cured of GSI. CONCLUSION: UDI-6 and IIQ-7 scores change after surgery for GSI and POP, with patients who are subjectively continent having lower postoperative scores on both scales.

Role of urethral electromyography in predicting outcome of Burch retropubic urethropexy.

OBJECTIVE: To establish preoperative urethral electromyographic parameters that predict which women are unlikely to be cured of genuine stress incontinence by Burch retropubic urethropexy procedures. STUDY DESIGN: Eighty-nine women who underwent preoperative urodynamic testing with urethral electromyography and retropubic urethropexy for genuine stress incontinence were prospectively studied. Raw electromyographic signals were processed by an electromyographic instrument equipped with automated motor unit analysis software programs. Quantitative electromyographic software was used to analyze the electrical activity of the urethral sphincter with use of mean rectified voltage (MRV)-mean amplitude calculated over the entire tracing after the waveform is rectified-with women at rest and during voluntary urethral squeezing, repetitive coughing, and bladder filling. Objective outcomes were determined 3 months after the operation with single-channel cystometrograms performed while subjects were standing. Nonparametric statistical analyses included the chi(2) test of association for nominal data and the Mann-Whitney test for comparison of population medians. RESULTS: All women had urethral hypermobility and met our standard clinical criteria for retropubic urethropexy. Fifteen women had incomplete follow-up data and were excluded from final analysis. Fifty-nine of 74 women (80%) were objectively cured, and 15 women had persistent genuine stress incontinence. Women who were cured did not differ from those who were not cured in age, parity, menopausal status, maximum urethral closure pressure, Valsalva leak point pressure, maximum cystometric capacity, detrusor instability, or prolapse stage. Women with persistent genuine stress incontinence were more likely to have had previous pelvic operations (P =.01). There were no differences in any electromyographic parameters at rest, with urethral squeezing, or during bladder filling between the groups. Women who were objectively cured had larger MRV values with repetitive coughing (P =.05) and larger increases from resting MRV values (DeltaMRV) with repetitive coughing (P =.04). Twenty-seven of 30 women with MRV values > or =25 microV with repetitive coughing were cured (positive predictive value [PPV] = 90%; negative predictive value [NPV] = 32%), and 22 of 24 women with more than a 10-microV increase in resting MRV values with repetitive coughing (DeltaMRV > 10 microV) were cured (PPV = 92%; NPV = 29%). If women had both an MRV value > or =25 microV and a DeltaMRV value >10 microV, the PPV was 100%; however, the NPV remained at 30%. CONCLUSION: Women who were cured of genuine stress incontinence with Burch retropubic urethropexy procedures had better motor unit action potential activation with repetitive coughing than women with persistent genuine stress incontinence. Urethral electromyography may be used to assess the neuromuscular integrity of the striated urethral sphincter and to help predict which women will have successful retropubic urethropexy procedures.

Donor fascia in urogynaecological procedures: a canine model.

OBJECTIVE: To explore the in vivo characteristics of donor fascia used in urogynaecological procedures, in a canine model. MATERIALS AND METHODS: Two experiments were conducted. In the first, donor fascia grafts were obtained from 12 dogs, the grafts freeze-dried and half were irradiated. The grafts were used for sacrocolpopexy and suburethral slings in each of five dogs. The dogs were killed at 2, 6 and 12 weeks after graft implantation, the grafts retrieved and assessed using tensilometry. In the second experiment, unirradiated sacrocolpopexy grafts were implanted in eight dogs; four grafts were placed under no tension and four under moderate tension. At 8 weeks, the grafts were retrieved and assessed by tensilometry. Measures of strength in both experiments included the ultimate tensile strength, ultimate strain and stiffness. All measures were compared using Kruskal-Wallis nonparametric tests in both studies. RESULTS: In the first experiment, a significant minority (23%) of grafts had complete loss of strength. Measures of graft strength did not vary when analysed according to donor dog, host dog, history of graft irradiation, duration of implantation or location of graft. In the second experiment, grafts placed under no tension tended to have lower tensile strength (chi2(1) = 3.125, P = 0.077), lower stiffness (chi2(1) = 3.125, P = 0.077) and lower ultimate strain (chi 2(1) = 3.182, P = 0.074). CONCLUSION: Graft irradiation as an isolated variable did not predispose grafts to failure in vivo. Biomechanical factors at the implantation site are likely to play a critical role in determining ultimate graft strength.

The etiology of urinary retention after surgery for genuine stress incontinence.

Transient postoperative urinary retention after stress incontinence surgery is common, and there is no widely accepted method of hastening the return to normal voiding. The etiology of this retention is poorly understood. Failure of the relaxation of the striated external urethral sphincter has been proposed as an etiologic agent, but has not been documented. Ten patients about to undergo a Burch colposuspension or sub-urethral sling, who demonstrated normal preoperative voiding, were recruited to a study of postoperative retention. Hook-wire electromyographic (EMG)probes were placed into the external urethral sphincter while the patients were under anesthesia, and a suprapubic catheter was placed. We performed instrumented voiding trials 1 or 2 days after surgery while continuously recording urethral EMG and intravesical pressure. Two patients demonstrated normal voiding. Two patients were able to void but demonstrated no EMG silencing. Six patients were unable to void and demonstrated persistent EMG activity. Four of these demonstrated no detrusor contraction, whereas two demonstrated detrusor contractions. All patients resumed normal voiding by clinical parameters within 14 days of surgery. Our study supports other research that suggests that failure of relaxation of the striated urethral sphincter contributes to postoperative urinary retention.

Myosin isoforms in female human detrusor.

The aim of this study was to document the relative proportions of two isoforms of myosin heavy chain in detrusor smooth muscle of women with detrusor overactivity and in asymptomatic controls. Women aged 35-65 with documented detrusor overactivity and without a history of neurologic disease, prior incontinence surgery, elevated post-void residual urine volume, or indwelling urinary catheter were eligible for the study. Full-thickness biopsies of extraperitoneal bladder dome were obtained at the time of laparotomy in six patients with documented detrusor overactivity and in a control group of eight continent patients. Biopsies were frozen in liquid nitrogen, crushed with a frozen mortar and pestle at -80 degrees C, and homogenized in buffer, and the extracts were electrophoresed on 6% polyacrylamide sodium dodecyl sulfate gels and stained with Coomassie blue. The gels were de-stained and then the protein bands were scanned with a densitometer. The mean patient age was 48 years (range, 36-59). Seven patients were Caucasian and seven patients were African American. Detrusor smooth muscle contains a mean of 34% (range, 27-43%) SM1 and 66% (range, 57-73%) SM2 isoforms. There was no difference in isoform composition when patients were compared according to urogynecologic diagnosis or according to race. In detrusor biopsies from women, approximately 34% of myosin is of the SM1 isoform and approximately 66% is of the SM2 isoform. This ratio is relatively constant in the two races studied and unchanged in women with detrusor overactivity. Animal models utilizing outlet obstruction of the bladder to provoke detrusor instability and detrusor hypertrophy are known to alter myosin isoform distribution and may not be appropriate models of detrusor instability in human females.

Postoperative resolution of urinary retention in patients with advanced pelvic organ prolapse.

OBJECTIVE: This study was undertaken to determine whether surgery for advanced pelvic organ prolapse corrects the voiding dysfunction commonly associated with this condition and if so to evaluate the ability of preoperative voiding studies to predict such correction. STUDY DESIGN: We reviewed the records of all women who underwent surgery at our center between January 1996 and June 1999 for stage 3 or 4 pelvic organ prolapse. Patients were included in this review if they had a postvoid residual volume of >100 mL documented by catheterization on at least 2 occasions, had no normal postvoid residual volumes documented, and had undergone preoperative multichannel urodynamic testing that included an instrumented voiding study. Demographic and urodynamic data were analyzed for the ability to predict whether the elevated postvoid residual volume would be resolved after surgery. RESULTS: Thirty-five patients satisfied the criteria for inclusion in the review. Twenty-six had stage 3 pelvic organ prolapse and 9 had stage 4 pelvic organ prolapse. The mean preoperative postvoid residual volume was 226 mL (range, 105-600 mL). Thirty-one patients (89%) had normal postvoid residual volumes after surgery. As a predictor of elevated postoperative postvoid residual volumes, the preoperative voiding study (performed with the prolapse reduced) had a sensitivity of 66%, a specificity of 46%, a positive predictive value of 12%, and a negative predictive value of 93%. CONCLUSION: In our center a preoperative voiding study performed with the pelvic organ prolapse reduced most accurately predicted postoperative voiding function when results of the voiding study were normal. Most patients with advanced pelvic organ prolapse and elevated postvoid residual volume had normalization of the postvoid residual volume after surgical correction of the pelvic organ prolapse.

The fate of rectus fascia suburethral slings.

OBJECTIVE: Autologous rectus fascia is commonly used to construct suburethral slings for the treatment of genuine stress incontinence. This fascia performs well and has not been associated with clinical problems related to its choice as a sling material. However, the histologic appearance of such slings after implantation has not been documented. STUDY DESIGN: At the time of revision of autologous rectus fascia suburethral slings in 5 patients, biopsy specimens of the slings were obtained and submitted for histologic examination. A specimen of rectus fascia before implantation was also obtained from a sixth patient who had no symptoms. RESULTS: After implantation autologous rectus fascia slings remain viable. There is fibroblast proliferation, neovascularization, and remodeling of the graft. No evidence of inflammatory reaction or of graft degeneration was detected. A linear orientation of connective tissue and fibroblasts was seen in some areas, whereas other areas had remodeled to form tissue similar to noninflammatory scar. CONCLUSION: Autologous rectus fascia slings undergo extensive remodeling after implantation.

Complex repetitive discharges during urethral sphincter EMG: clinical correlates.

Complex repetitive discharges (CRDs) are a form of abnormal needle electromyographic (EMG) activity associated with a variety of neuromuscular disorders, including chronic denervation. Urethral CRDs have also been associated with symptoms of voiding dysfunction. We reviewed the findings of 351 consecutive urethral sphincter EMG studies to characterize the patients with CRDs in our patient population and further to characterize the peri-operative course of any patient with urethral CRDs who underwent surgery for genuine stress incontinence (GSI). Among the 351 women studied, a subgroup of 27 (8%) women demonstrated CRDs during their study. Patients with CRDs were more likely to report the symptom of strain voiding (48% of patients with CRDs, 18% of patients without CRDs; chi(2)((1)) = 17.6, P < 0.001). Patients with CRDs were also more likely to have undergone prior urethral dilation (15% of patients with CRDs versus 2% of patients without CRDs, chi(2)((1)) = 9.5, P < 0.01). Patients with CRDs were similar to patients without CRDs with respect to symptoms of incontinence and history of hysterectomy or surgery for incontinence. Ten patients who had urethral CRDs underwent surgery for their GSI with a 90% success rate. The duration of post-operative catheterization did not differ from that of our general population of patients undergoing similar procedures. Urethral CRDs appear to be a non-specific finding, and it is premature to alter the approach to patients with lower urinary tract dysfunction for this reason.

Urethral collagen morphologic characteristics among women with genuine stress incontinence.

OBJECTIVE: This was a study of the morphologic characteristics of urethral collagen in women with stress incontinence and continent control women. STUDY DESIGN: Urethral needle biopsy specimens were obtained from 31 women. Fifteen women were continent, and the other 16 had undergone full urogynecologic assessment for symptoms of urinary incontinence. Biopsy specimens were assessed under electron microscopy. Mean collagen fibril diameter was measured and collagen morphologic characteristics were assessed. RESULTS: The biopsy specimens from 30 women were included in the analysis. Collagen fibril diameter did not vary with continence status, the presence of pelvic organ prolapse, age, race or hormonal status. Alterations in collagen fibril morphologic characteristics were evident in the biopsy specimens from nine patients with incontinence. The alterations in collagen morphologic characteristics fell into three patterns, which for convenience were referred to as the obscured pattern, the dense pattern, and the degenerative pattern. CONCLUSION: Altered collagen morphologic characteristics are found in some patients with stress incontinence, and possible causes for those alterations are suggested by their appearances.

Ultrastructure of detrusor and urethral smooth muscle in women with urinary incontinence.

OBJECTIVE: We performed a quantitative study to determine whether mixed urinary incontinence was associated with any ultrastructural changes in detrusor and urethral smooth muscle. STUDY DESIGN: Detrusor and urethral smooth muscle biopsy specimens were obtained at the time of laparotomy from 5 women aged 35 to 65 years with mixed urinary incontinence and from a control group of 5 continent women. Smooth muscle morphologic characteristics were assessed from a systematic random sample of electron micrographs. A further 16 urethral biopsy specimens were similarly analyzed to confirm the findings of the initial study. RESULTS: The electron-dense portion of the sarcolemma was smaller in urethral biopsy specimens taken from patients with intrinsic sphincter deficiency than in those from control subjects (chi(2)((1)) = 4.9; P =.027). No other morphologic characteristics were unique to patients with incontinence. CONCLUSIONS: Our study suggests that focal adhesion architecture is decreased in urethral smooth muscle of patients with intrinsic sphincter deficiency.

Functional failure of fascia lata allografts.

OBJECTIVES: Fascia lata allografts are commonly used in urogynecologic procedures. Functional failure of several grafts has occurred, and such failure has been recognized as a materials problem in 12 patients. STUDY DESIGN: Twelve patients with failure of an initial urogynecologic procedure performed with irradiated and freeze-dried donor fascia lata grafts underwent reoperation. Portions of the implanted fascia lata grafts could be retrieved in 7 cases. Graft specimens underwent histologic processing followed by hematoxylin and eosin staining. RESULTS: Histopathologic analyses of the retrieved material demonstrated several ongoing processes in the failed grafts. A few grafts showed areas of ideal remodeling. Most grafts, however, showed areas of disorganized remodeling and areas of graft degeneration. Evidence of immune reaction to the graft was observed in some cases. CONCLUSION: The high materials failure rate associated with the use of irradiated and freeze-dried donor fascia lata grafts suggests that such tissue should not be used for urogynecologic procedures.

Failure of allograft suburethral slings.

OBJECTIVES: To report our experience of using freeze-dried irradiated fascia lata allografts for suburethral sling procedures. PATIENTS AND METHODS: Between December 1996 and September 1998, 35 patients (mean age 60.25 years, range 37-79) underwent suburethral sling placement with fascia allograft. These patients were reviewed, with the findings at the time of any surgical re-exploration. Eleven (31%) had undergone prior surgery for genuine stress incontinence and 32 (91%) had a preoperative diagnosis of intrinsic sphincter deficiency. RESULTS: On re-operation for persistent or recurrent stress incontinence, the allograft was present but grossly degenerated in two (6%) patients and completely absent in five (14%) patients. Histology of a retrieved graft fragment showed both fibroblast proliferation and degeneration within the graft. CONCLUSION: The use of freeze-dried, irradiated fascia lata for suburethral sling procedures was associated with a material failure rate of >/=20%. We caution against its use in this setting.