A comparison of two intravesical bladder instillations for interstitial cystitis/bladder pain syndrome.

OBJECTIVE: Bladder pain syndrome (BPS) is a chronic pain condition associated with injury to the glycosoaminoglycan (GAG) layer. We aimed to prospectively evaluate iAluRil® with multi-centre tertiary urogynaecology collaboration. We hypothesised that iAluRil® (a GAG therapy) would demonstrate equivalent symptom, pain and QOL scores compared to DMSO controls. STUDY DESIGN: iAluRil® was administered for 7 instillations over 3 months in 34 women over 6 sites. 18 historical DMSO controls were matched 2:1. At baseline and 3 months post treatment validated questionnaires were collected. RESULTS: Both iAluRil® and DMSO were associated with statistically significant improvements in IC/BPS specific questionnaire scores. iAluRil® showed statistically significant improvements in pain, symptoms, and QOL. 45 % of iAluRil® recipients had a greater than 50 % reduction in pain score as represented by the VAS. DMSO was also effective in improving measures of IC/BPS with statistically significant decreases in ICSI and ICPI. There was no statistically significant difference in the size of the effect between DMSO and IAluRil®. CONCLUSIONS: iAluRil® is well tolerated and associated with significant improvements in pain and symptom scores. Almost half of refractory BPS will have a 50 % decrease in pain score at three months post treatment. This effect size is similar to DMSO.

Video and review of the surgical management of recurrent urethral diverticulum.

INTRODUCTION: Recurrent urethral diverticulum has been reported in 23% of cases after primary repair and can be difficult to manage. The aim of this video is to demonstrate a surgical technique of repairing a recurrent diverticulum in a woman who had two previous procedures, one with a Martius labial fat pad graft. METHODS: A 40-year-old woman presented with a symptomatic recurrent urethral diverticulum after two previous repairs. She underwent surgery with excision of the diverticular mucosa and multilayer urethral closure using the diverticulum wall after mobilization and then repositioning of the Martius labial fat pad interposition. RESULTS: There were no surgical complications intra- or postoperatively, and the patient had improvement of her symptoms postoperatively with resolution of the diverticulum on ultrasound. CONCLUSIONS: Mobilizing and repositioning a Martius labial fat pad is a feasible technique for complex recurrent urethral diverticulum repairs. The graft alone without meticulous urethral repair will not prevent diverticulum recurrence, fistula formation or stress urinary incontinence. This procedure requires experienced surgeons to minimize surgical complications and optimize outcome.

Composite mesh design for delivery of autologous mesenchymal stem cells influences mesh integration, exposure and biocompatibility in an ovine model of pelvic organ prolapse.

The widespread use of synthetic transvaginal polypropylene mesh for treating Pelvic Organ Prolapse (POP) has been curtailed due to serious adverse effects highlighted in 2008 and 2011 FDA warnings and subsequent legal action. We are developing new synthetic mesh to deliver endometrial mesenchymal stem cells (eMSC) to improve mesh biocompatibility and restore strength to prolapsed vaginal tissue. Here we evaluated knitted polyamide (PA) mesh in an ovine multiparous model using transvaginal implantation and matched for the degree of POP. Polyamide mesh dip-coated in gelatin and stabilised with 0.5% glutaraldehyde (PA/G) were used either alone or seeded with autologous ovine eMSC (eMSC/PA/G), which resulted in substantial mesh folding, poor tissue integration and 42% mesh exposure in the ovine model. In contrast, a two-step insertion protocol, whereby the uncoated PA mesh was inserted transvaginally followed by application of autologous eMSC in a gelatin hydrogel onto the mesh and crosslinked with blue light (PA + eMSC/G), integrated well with little folding and no mesh exposure. The autologous ovine eMSC survived 30 days in vivo but had no effect on mesh integration. The stiff PA/G constructs provoked greater myofibroblast and inflammatory responses in the vaginal wall, disrupted the muscularis layer and reduced elastin fibres compared to PA + eMSC/G constructs. This study identified the superiority of a two-step protocol for implanting synthetic mesh in cellular compatible composite constructs and simpler surgical application, providing additional translational value.

A cross-sectional study to identify a set of risk factors for caprine herpesvirus 1 infection.

BACKGROUND: Caprine herpesvirus 1 (CpHV-1) causes neonatal mortality and reproductive failure in goats. Despite its impact on herd reproductive performance, few studies have investigated the risk factors associated with CpHV-1 infection. The aim of this cross-sectional study was to identify potential herd- and host-level risk factors associated with CpHV-1 prevalence in a goat population with heterogeneous seropositivity for CpHV-1. RESULTS: Blood samples and individual data from 4542 goats were collected from 255 herds in Piedmont, Italy. Enzyme-linked immunosorbent assay (ELISA) and serum neutralization tests were carried out to detect antibodies against CpHV-1. A mixed-effects model was applied to identify any statistical association between CpHV-1 seropositivity and a set of putative host-level and herd-level risk factors. A total of 630 samples tested were found positive by ELISA (prevalence = 13.9%; 95% confidence interval (CI) 12.9-14.9). Of the 255 tested herds, 85 were classified as positive for the presence of at least one gB-positive animal (herd prevalence 33.3%, 95% CI 27.5-39.2), with a within-herd prevalence between 0.7 and 100% (Q1 = 17.6%; median = 32.3%; Q3 = 50%) (Q = quartiles). The prevalence ratios showed a statistical association with the following risk factors: breeds other than Saanen, older age, larger herd size, meat and extensive herds, and co-existence of CAEV-infected animals. CONCLUSIONS: Results from this cross sectional study may help to elucidate the natural history of the infection and inform targeted strategies to control a disease with a potentially important impact on animal health and goat farming economy.

Hepatitis E Virus: A Cross-Sectional Serological and Virological Study in Pigs and Humans at Zoonotic Risk within a High-Density Pig Farming Area.

An increase in autochthonous hepatitis E virus (HEV) infections has been recorded in Italy suspected to be zoonotically transmitted from pigs; this study was carried out to determinate the seroprevalence and risk factors associated with hepatitis HEV exposition, both in swine and humans working in pig farms, located within a high-density pig farming area in Piedmont region, north-western Italy. The presence of viral RNA in human and swine samples was also evaluated, and phylogenetic analysis was performed on HEV-positive samples. Forty-two swine farms were sampled; 142 workers were enrolled in the study and classified into two groups: (i) 69 workers with occupational contact with swine (including veterinarians and farmers) recruited in the 42 sampled farms; (ii) 73 without occupational contact with swine. Forty-one of 42 (97%) swine farms resulted positive to enzyme-linked immunosorbent assay test for HEV antibodies (Abs). Overall seroprevalence in swine was 50% (441/879), with seropositivity rate higher in sows (333/469, 71%). HEV RNA in stool samples was detected in animals from 13 of 42 tested farms (31%), and a higher positivity resulted in weaners (40/246, 16.3%). Phylogenetic analysis classified all HEV isolates within genotype 3 (subtypes 3f, 3e, 3c). All humans were negative for HEV viral genome in blood. Five of 142 sera were positive for IgG anti-HEV with an overall prevalence of 3.52% with no statistically significant differences in prevalence rates between workers at zoonotic risk and the control group (5.7% versus 1.3%). In contrast, a significant difference (OR 10.1) was observed within the subgroup including subjects exposed for short periods (veterinarians) compared with those who worked for long periods (farmers) suggesting a correlation between the time of exposure and the likelihood of HEV infection. Reporting HEV infection is not mandatory in Italy, but a constant epidemiological surveillance should be ensured to clarify the epidemiology of this disease.

Temporal changes in the biomechanical properties of endometrial mesenchymal stem cell seeded scaffolds in a rat model.

Use of synthetic clinical meshes in pelvic organ prolapse (POP) repair can lead to poor mechanical compliance in vivo, as a result of a foreign body reaction leading to excessive scar tissue formation. Seeding mesh with mesenchymal stem cells (MSCs) prior to implantation may reduce the foreign body reaction and lead to improved biomechanical properties of the mesh-tissue complex. This study investigates the influence of seeding human endometrial mesenchymal stem cells (eMSCs) on novel gelatin-coated polyamide scaffolds, to identify differences in scaffold/tissue biomechanical properties and new tissue growth following up to 90 days' implantation, in a subcutaneous rat model of wound repair. Scaffolds were subcutaneously implanted, either with or without eMSCs, in immunocompromised rats and following 7, 30, 60 and 90 days were removed and assessed for their biomechanical properties using uniaxial tensile testing. Following 7, 30 and 90 days' implantation scaffolds were assessed for tissue ingrowth and organization using histological staining and scanning electron microscopy. The eMSCs were associated with altered collagen growth and organization around the mesh filaments of the scaffold, affecting the physiologically relevant tensile properties of the scaffold-tissue complex, in the toe region of the load-elongation curve. Scaffolds seeded with eMSCs were significantly less stiff on initial stretching than scaffolds implanted without eMSCs. Collagen growth and organization were enhanced in the long-term in eMSC-seeded scaffolds, with improved fascicle formation and crimp configuration. Results suggest that neo-tissue formation and remodelling may be enhanced through seeding scaffolds with eMSCs.

Mesenchymal stem/stromal cells in post-menopausal endometrium.

STUDY QUESTION: Does post-menopausal endometrium contain mesenchymal stem/stromal cells (MSC) that have adult stem cell properties and can be prospectively isolated from a biopsy? SUMMARY ANSWER: Perivascular W5C5(+) cells isolated from post-menopausal endometrial biopsies displayed characteristic MSC properties of clonogenicity, multipotency and surface phenotype irrespective of whether the women were or were not pre-treated with estrogen to regenerate the endometrium. WHAT IS KNOWN ALREADY: Recently MSCs have been identified in human premenopausal endometrium, and can be prospectively isolated using a single marker, W5C5/SUSD2. STUDY DESIGN, SIZE, DURATION: Endometrial tissue of both the functional and basal layers, from 17 premenopausal (pre-MP) women, 19 post-menopausal (post-MP) women without hormonal treatment and 15 post-menopausal women on estrogen replacement therapy (post-MP+ E2), was collected through a prospective phase IV clinical trial over 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Post-menopausal women <65 years of age were treated with or without E2 for 6-8 weeks prior to tissue collection. Serum E2 levels were determined by estradiol immunoenzymatic assay. Endometrial tissue was obtained from women by biopsy (curettage) just prior to the hysterectomy. The effect of E2 on endometrial thickness and glandular and luminal epithelial height was determined using image analysis. Endometrial tissue was dissociated into single cell suspensions and MSC properties were examined in freshly isolated and short-term cultured, magnetic bead-purified W5C5(+) cells. MSC properties were assessed using clonogenicity, serial cloning, mesodermal differentiation in adipogenic, chondrogenic, osteogenic and myogenic induction culture media, and surface phenotype analysis by flow cytometry. Estrogen receptor α expression in W5C5(+) cells was examined using dual colour immunofluorescence. Vascularity was analysed using CD34 and alpha smooth muscle actin immunostaining and subsequent image analysis. MAIN RESULTS AND THE ROLE OF CHANCE: A small population of stromal cells with MSC properties was purified with the W5C5 antibody from post-menopausal endometrium, whether atrophic from low circulating estrogen or regenerated from systemic estrogen treatment, similar to premenopausal endometrium. The MSC derived from post-menopausal endometrium treated with or without E2 fulfilled the minimum MSC criteria: clonogenicity, surface phenotype (CD29(+), CD44(+), CD73(+), CD105(+), CD140b(+), CD146(+)) and multipotency. The post-menopausal endometrial MSCs also showed comparable properties to premenopausal eMSC with respect to self-renewal in vitro and W5C5 expression. The W5C5(+) cells were located perivascularly as expected and did not express estrogen receptor α. LIMITATIONS, REASONS FOR CAUTION: The properties of the MSC derived from post-menopausal endometrium were evaluated in vitro and their in vivo tissue reconstitution capacity has not been established as it has for premenopausal endometrial MSC. WIDER IMPLICATIONS OF THE FINDINGS: The endometrium is an accessible source of MSC obtainable with minimum morbidity that could be used for future clinical applications as a cell-based therapy. This study shows that menopausal women can access their endometrial MSC by a simple biopsy for use in autologous therapies, particularly if their endometrium has been regenerated by short-term E2 treatment, provided they have an intact uterus and are not contraindicated for short-term E2 treatment. Endometrial MSC in post-menopausal women possess key MSC properties and are a promising source of MSC independent of a woman's age. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia grant (1021126) (C.E.G., A.R.) and Senior Research Fellowship (1042298) (C.E.G.), Australian Gynaecological Endoscopic Society grant (A.R.) , Monash International Postgraduate Research Scholarship (DU), Australian Stem Cell Centre, South East Melbourne Alliance for Regenerative Therapies and Australian Stem Cell Centre top up scholarships (DU) and Victorian Government's Operational Infrastructure Support Program. Competing interests: AR receives Preceptorship fees from AMS, advisory board fees and sponsored study from Astellas, and conducts investigator led studies sponsored by AMS and Boston Scientific for other projects. TRIAL REGISTRATION NUMBER: CTNRN12610000563066.

Detection of border disease virus (BDV) genotype 3 in Italian goat herds.

In January 2011, cases of abortion, stillbirth and weak live kids were reported in two goat herds in northern Italy. Samples from 18 kids found dead, 12 fetuses, and two stillborn kids were analyzed for pestivirus antigen using an ELISA kit and a border disease virus (BDV)-specific RT-PCR. Positive results were obtained in six kids and one fetus. Phylogenetic analysis based on 225 bp of the 5'UTR fragment of the BDV genome from positive samples showed that the goats were infected with BDV genotype 3. Serum and blood samples collected from all animals in both herds were analyzed using competitive ELISA to detect p80 antibodies and RT-PCR to detect viraemia. Pestivirus antibodies were detected in 61/67 goats in herd A and in 38/169 in herd B. A persistently infected (PI) goat was found in herd A. The PI animal was submitted to the laboratory for BDV diagnosis with Ag-ELISA, viral isolation, and nested RT-PCR on tissue samples from the spleen, kidney, brain, liver, lung, ileocaecal valve, mesenteric lymph nodes, and skin. All of the tests were positive for BDV in each of the tissues analyzed. The BDV sequence of the PI was identical to BDV sequences found in other positive animals. This is the first description of a BDV PI goat and the first evidence of BDV genotype 3 circulation in Italy. The study raises questions about the real impact this virus has on breeding goats.

Anterior compartment mesh: a descriptive study of mesh anchoring failure.

OBJECTIVES: To define types of support failure after anterior compartment mesh placement and to investigate any association with predictors of recurrence. METHODS: This was a retrospective study on patients ≥ 3 months after anterior mesh placement. All patients underwent a standardized interview, clinical examination using the International Continence Society Pelvic Organ Prolapse Quantification system (ICS POP-Q) and three-dimensional/four-dimensional (3D/4D) translabial ultrasound. Mesh failure was defined as recurrence of anterior/central compartment prolapse seen on ultrasound. Failures were classified as anterior, global and apical. Their association with hiatal area on Valsalva maneuver and levator avulsion was tested. RESULTS: Three hundred and one patients were seen initially, of whom five were excluded because of missing data, leaving 296. Mean follow-up was 1.8 (range, 0.3-5.6) years. Mean age was 65 (range, 32-88) years. One hundred and thirty-nine (47%) women were fitted with a Perigee mesh, 66 (22%) with an Anterior Prolift mesh and 91 (31%) with an Anterior Elevate mesh. Recurrent symptoms (lump/drag) were reported in 65 (22%), a recurrent cystocele was noted in 128 clinically (43%) and in 105 on ultrasound (35%). Avulsion was diagnosed in 117 patients (40%). Mean hiatal area on Valsalva was 33.3 (range, 14.1-60.0) cm2. Mesh failure was diagnosed in 112 patients (38%), comprising global failure in 81 (27%), apical failure in 23 (8%) and anterior failure in eight (3%). Apical and global failures were significantly associated with hiatal area, associations that remained after controlling for potential confounders. CONCLUSIONS: Mesh failure, i.e. anterior or central compartment recurrent prolapse, was noted in 38% of patients on average 1.8 years after placement of anterior compartment mesh. Global and apical failures together constituted 93% of all mesh failures, both types of failure being significantly associated with hiatal area on Valsalva maneuver.

Persistence of urgency and urge urinary incontinence in women with mixed urinary symptoms after midurethral slings: a multivariate analysis.

OBJECTIVE: To determine risk factors for persistence of urgency or urge urinary incontinence following midurethral sling surgery. DESIGN: Prospective cohort study. SETTING: Tertiary referral Urogynaecology Unit. SAMPLE: A total of 754 consecutive women with stress urinary incontinence (SUI) and urgency; and 514 women with SUI and urge urinary incontinence (UUI) who underwent midurethral sling with a mean follow up of 50 months. METHODS: Women with persistent urgency or UUI at long-term follow up were compared with those whose symptoms had resolved, using multivariate analysis to determine the risk factors for persistent symptoms. MAIN OUTCOMES MEASURES: Odd ratios (OR) of independent risk factors for persistent urgency or UUI. RESULTS: Persistent urgency (304/754, 40%) and UUI (166/514, 32%) were common. Coexistent detrusor overactivity (OR 2.04, 95% CI 1.39-3.01), baseline symptom severity (OR 1.41, 95% CI 1.10-1.78) and age (OR 1.03, 95% CI 1.02-1.04) increased the risk of persistent urgency, while transobturator sling surgery (OR 0.61, 95% CI 0.39-094) and concomitant prolapse surgery (OR 0.54, 95% CI 0.38-0.75) decreased the risk. For UUI detrusor overactivity (OR 1.86, 95% CI 1.18-2.93), baseline symptom severity (OR 1.88, 95% CI 1.38-2.56), previous incontinence surgery (OR 2.18, 95% CI 1.28-3.70) increased the risk of persistence, whereas apical prolapse surgery (OR 0.33, 95% CI 0.15-0.70) decreased the risk. Women were more likely not to recommend surgery when they experienced persistent urgency (15.8% versus 2.7%, P < 0.0001) or UUI (24.7% versus 2.9%, P < 0.0001). CONCLUSIONS: Urodynamic parameters, baseline urgency symptom severity, midurethral sling route and concomitant prolapse operation are important predictors of persistent urgency or UUI following midurethral sling.

Laparoscopic versus open Burch colposuspension: a randomised controlled trial.

OBJECTIVE: To compare perioperative characteristics, short-term, and long-term outcomes for laparoscopic Burch colposuspension (LBC) and open Burch colposuspension (OBC) for the treatment of urinary stress incontinence. DESIGN: Randomised surgical trial with single blinding. SETTING: Three tertiary level teaching hospitals involving seven surgeons of varying skill levels. POPULATION: Two hundred women with urodynamic stress incontinence (USI). METHODS: The two groups were treated in identical fashion, except for the laparoscopic or open approach to surgery. Attempts were made to blind the subjects and the observers obtaining outcome data to treatment group. Analyses were adjusted for surgeon experience. MAIN OUTCOME MEASURES: Absence of USI 6 months following surgery, postoperative pain, time spent in hospital, and time to return to activities of normal daily living. RESULTS: There were no significant differences in objective and subjective measures of cure and in patient satisfaction at 6 months, 24 months, or 3-5 years of follow up between laparoscopic and open colposuspension groups. Laparoscopic colposuspension took longer time to perform (87 versus 42 minutes, P< 0.0001) but was associated with less blood loss (P = 0.03), less pain (P = 0.02), and quicker return to normal activities (P = 0.01). CONCLUSION: LBC has significant advantages over traditional OBC, without any apparent compromise in short-term and long-term outcomes. To compare perioperative characteristics, short-term, and long-term outcomes for laparoscopic Burch colposuspension (LBC) and open Burch colposuspension (OBC) for the treatment of urinary stress incontinence. Randomised surgical trial with single blinding. Three tertiary level teaching hospitals involving seven surgeons of varying skill levels. Two hundred women with urodynamic stress incontinence (USI). The two groups were treated in identical fashion, except for the laparoscopic or open approach to surgery. Attempts were made to blind the subjects and the observers obtaining outcome data to treatment group. Analyses were adjusted for surgeon experience. Absence of USI 6 months following surgery, postoperative pain, time spent in hospital, and time to return to activities of normal daily living. There were no significant differences in objective and subjective measures of cure and in patient satisfaction at 6 months, 24 months, or 3-5 years of follow up between laparoscopic and open colposuspension groups. Laparoscopic colposuspension took longer time to perform (87 versus 42 minutes, P < 0.0001) but was associated with less blood loss (P= 0.03), less pain (P= 0.02), and quicker return to normal activities (P= 0.01). LBC has significant advantages over traditional OBC, without any apparent compromise in short-term and long-term outcomes.

Transdermal posterior tibial nerve laser therapy is not effective in women with interstitial cystitis.

PURPOSE: Interstitial cystitis (IC) is a debilitating condition which causes irritative bladder symptoms, pain and a decrease in health status. The pathophysiology is poorly understood so therapeutic options are diverse. Percutaneous posterior tibial nerve stimulation is an effective treatment and pulsed transdermal laser stimulation is an established technique for pain management. We evaluated the efficacy of transdermal laser stimulation of the posterior tibial nerve for patients with IC. MATERIALS AND METHODS: Women meeting the National Institutes of Health National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC were prospectively recruited and randomized to treatment (29) or placebo (27) cohorts in a double-blind trial. At home the patient performed laser therapy daily for 30 seconds over the SP6 acupuncture point for 12 weeks. Measures at baseline and at 84-day followup included the 7-day voiding diary, the Interstitial Cystitis Problem Index, Interstitial Cystitis Symptom Index and RAND 36-Item Health Survey questionnaires. RESULTS: There were no significant differences between the treatment and control cohorts on any of the measures. However, there was a significant decrease between baseline and 12-week followup in the amount voided, symptom problems and severity, and on all 8 SF-36 scales. There was no significant effect of fluid intake. CONCLUSIONS: This study demonstrated no difference between the active and sham device. However, it is interesting that treatment and control cohorts experienced similar improvements, suggesting that the control cohort improvements may have been due to participants' belief that they were receiving active treatment from the stimulator. These findings provide support for investigating placebo effects in randomized trials.

Urinary levels of substance P and its metabolites are not increased in interstitial cystitis.

OBJECTIVES: To determine whether interstitial cystitis is associated with the increased release of substance P from the bladder wall into urine, by measuring urinary excretion rates of substance P and its metabolites in women with interstitial cystitis and in a control group of women with stress incontinence and normal bladder function. PATIENTS AND METHODS: Catheter urine was collected from 13 patients and 10 controls during a water diuresis ( approximately 10 mL/min) before and after instilling the bladder with 100 mL of water. The contribution of the bladder wall to urinary substance P peptides was assessed by measuring the change in substance P peptide levels after 2 min of bladder stasis before and after instillation. RESULTS: Absolute substance P excretion rates were similar in patients with interstitial cystitis and controls; 2 min of bladder stasis reduced the substance P excretion rate (P = 0.03) and increased the excretion rate of substance P metabolites (P = 0.01). CONCLUSIONS: The release of substance P from the bladder wall was not increased in patients with interstitial cystitis.

Pathophysiology of interstitial cystitis.

Despite being described over 80 years ago, interstitial cystitis remains a disease of undetermined aetiology and poor treatment outcomes. Generally agreed diagnostic criteria of this condition, which occurs primarily in females, are frequency, urgency and pain, a low-capacity hypersensitive bladder, and mucosal haemorrhages and tearing on bladder distention. Although current theories of pathophysiology are predominantly conjecture, important elements of the disease process are increased afferent and efferent neuronal activity, an excess of inflammatory mediators, increased epithelial permeability and possibly reduced bladder vascularity. Improved treatment outcome will follow a better understanding of pathophysiology.

Activation of the kallikrein kinin system in interstitial cystitis.

PURPOSE: We investigated whether the kallikrein kinin system is activated in interstitial cystitis by measuring urinary excretion rates of kinin peptides, active and total kallikrein, and the kininase neutral endopeptidase in women with interstitial cystitis. We compared these excretion rates to a control group of women with stress incontinence and normal bladder function. MATERIALS AND METHODS: Catheter urine was collected from subjects during a water diuresis (approximately 10 ml. per minute) before and after distention of the bladder with 100 ml. water. The contribution of the bladder wall to urinary kinins was assessed by measuring the change in kinin levels after 2 minutes of bladder stasis before and after distention. RESULTS: Absolute bradykinin and kallidin excretion rates were similar in women with interstitial cystitis and control subjects. Two minutes of bladder stasis after bladder distention increased urinary bradykinin (p = 0.02) but not kallidin excretion rates. Active and total kallikrein excretion rates were similar in patients with interstitial cystitis and control subjects. Neutral endopeptidase excretion rates were reduced in the initial urine collection from subjects with interstitial cystitis but were similar in both groups during later collection periods. CONCLUSIONS: These data provide evidence for increased bradykinin levels in the bladder wall of subjects with interstitial cystitis, which may be due in part to reduced neutral endopeptidase levels. These increased bradykinin levels may participate in the pathogenesis and symptomatology of interstitial cystitis.

Bladder microvasculature in women with interstitial cystitis.

PURPOSE: A cardinal cystoscopic finding in women with interstitial cystitis is mucosal small vessel hemorrhage or glomerulations after hydrodistention. We quantified and compared microvascular density and endothelial proliferation in the bladder biopsies of women with interstitial cystitis and a control group of women who were undergoing incontinence or prolapse surgery. MATERIALS AND METHODS: We performed computer assisted image analysis and immunohistochemical studies to compare differences in the blood vessel count, and proportional area in the bladder suburothelium and deeper submucosa of bladder biopsies of 52 women, including 26 with interstitial cystitis. Routine light microscopy features were examined and correlated with microvascular density. RESULTS: In the bladder biopsies of women with interstitial cystitis there was a lower blood vessel count (p = 0.01), and a lower proportion of the total image consisted of blood vessel wall (p = 0.03) in the suburothelium than in control biopsies. We noted no difference in the blood vessel count of the deeper submucosa or in the degree of endothelial cell proliferation. Suburothelial blood vessel differences correlated with the degree of histological change, such as edema, inflammatory infiltrate and vascular congestion. CONCLUSIONS: We found decreased microvascular density in the suburothelium but not in the deeper submucosa in bladder biopsies of women with interstitial cystitis.

Suture injury to the urinary tract in urethral suspension procedures for stress incontinence.

The case histories of women attending the Urogynecology Department at the Royal Women's Hospital and Mercy Hospital for Women were reviewed between 1986 and 1998 to determine the incidence and postoperative morbidity caused by suture injury to the urinary tract following urethral suspension surgery for stress incontinence. In our department 1103 Burch colposuspensions and 61 Stamey urethral suspensions have been performed. Intraoperative cystourethroscopy was performed routinely for the early detection and treatment of urinary tract injury. Intravesical sutures were found by routine intraoperative cystoscopy in 1 Stamey suspension, 1 open Burch colposuspension and 3 laparoscopic Burch colposuspensions. Ureteric suture ligation was diagnosed in 2 women intraoperatively and 1 women postoperatively after laparoscopic Burch colposuspension. Two women presented with late complications from intravesical sutures following open Burch colposuspension. A further 7 women referred with urinary symptoms were found to have intravesical sutures, 2 following Burch colposuspension, 4 following Stamey urethral suspension and 1 following the Marshall-Marchetti-Kranz procedure. Seven of the 9 women diagnosed with intravesical sutures presented with bladder or pelvic pain, frequency or urinary tract infection. Two women had recurrent stress incontinence and were found to have a intravesical suture on routine cystoscopy at the time of stress incontinence surgery. Suture removal, with any accompanying calculus, was achieved cystoscopically with almost immediate resolution of symptoms without loss of urinary control in all cases. Non-absorbable intravesical sutures occurring as a result of suture misplacement or erosion is an infrequent but important complication of stress incontinence surgery, but should be suspected if pain and irritative bladder symptoms or recurrent urinary infection occur postoperatively. Cystourethroscopy performed intra-operatively or postoperatively is essential for early diagnosis and treatment.

Interstitial cystitis and the gynecologist.

Interstitial cystitis (IC) is a predominantly female condition with the presenting symptoms of frequency of micturition and pain. The diagnosis is confirmed by bladder visualization at cystoscopy during filling, emptying, and redistension. The epidemiology, proposed etiologies, and current therapies for interstitial cystitis are discussed. The condition of IC is poorly understood and has no specific histological characteristics. However, there is much that can be offered to the IC sufferer to relieve or cure her symptoms. It is hoped that the recent decade of increasing research activity will be fruitful in answering questions of etiology and pathogenesis, and offering hope for new therapies and ultimately cure.