Sexual function after vaginal and abdominal fistula repair.

OBJECTIVE: The purpose of this study was to compare clinical outcomes and sexual function between transvaginal and transabdominal repairs of vesicovaginal fistulae (VVF). STUDY DESIGN: Participants (99 women with VVF at a tertiary referral center) were treated with urinary catheterization for 12 weeks and, if the procedure was unsuccessful, underwent repair using either the transvaginal (Latzko) or transabdominal technique. Objective clinical parameters were analyzed; subjective outcomes were recorded prospectively before surgery and at the 6-month follow-up examination with the use of the female sexual function index to evaluate sexual function and the visual analog scale to measure general disturbance by the fistula. RESULTS: After bladder drainage for 12 weeks, 8 patients had spontaneous fistula closure. Demographic variables were similar in the transvaginal (n = 60) and transabdominal (n = 31) repair groups. The transvaginal procedure showed significantly shorter operation times, less blood loss, and shorter hospital stay. Continence rates 6 months after surgery were 82% (transvaginal) and 90% (transabdominal). Sexual function in the 64 sexually active patients was significantly improved, and overall disturbance by the fistula was reduced with both operative techniques. Neither surgical intervention was superior to the other regarding sexual function or visual analog scale. CONCLUSION: Fistula repair improves sexual function and quality of life with no difference attributable to surgical route. Given this and that operating time, blood loss and length of stay are less with the transvaginal approach, the transvaginal approach is preferred in VVF repair if fistula and patient characteristics are suitable.

Prolapse and sexual function 8 years after neovagina according to Shears: a study of 43 cases with Mayer-von Rokitansky-Küster-Hauser syndrome.

INTRODUCTION AND HYPOTHESIS: To investigate sexual and anatomical outcome after Shears neovagina in patients with Mayer-von Rokitansky-Kuster-Hauser syndrome (MRKH). METHODS: Forty-three consecutive patients with MRKH syndrome underwent surgery creating a neovagina according to Shears. Follow-up was 8 years. Sexual function was assessed using the Female Sexual Function Index (FSFI) as patient reported outcome; anatomical results were assessed measuring anterior, posterior and apical prolapse using the ICS Pelvic Organ Prolapse Score (ICS-POP Score). Pelvic floor contraction was measured applying the Oxford grading system. RESULTS: Thirty-seven of the patients were regularly sexually active and filled in the FSFI; mean total FSFI was 27.2 (range 24-28). No significant prolapse of the neovagina was noted, 11 patients had a grade I cystocele, rectocele or apical descent that was asymptomatic. Oxford grading of the pelvic floor contraction was 4 in median (range 2-5). CONCLUSION: The neovagina according to Shears is a valuable surgical option with good sexual and anatomical outcome 8 years after therapy.

The correlation of urethral resistance pressure with maximum urethral closure pressure and stress incontinence.

OBJECTIVE: Aim of the study was to correlate urethral retro resistance pressure with the maximum urethral closure pressure (MUCP) and functional urethral length (FUL) in patients with urinary incontinence and healthy individuals. STUDY DESIGN: Two hundred and twenty patients with the complaint of urinary incontinence had a urodynamic examination including urethral pressure profiles and URP. Additionally, 15 healthy individuals without the complaint of any incontinence had their URP and urethral pressure profiles measured. The correlation of MUCP, FUL and URP were calculated using Graph Pad Instat 4.0 for windows. RESULTS: URP correlates well with the diagnosis of urodynamic stress incontinence. Correlation coefficient between URP and MUCP is 0.9262. Healthy individuals have significantly higher values for URP and MUCP. CONCLUSION: URP is a valuable less invasive test than conventional urethral function tests for the diagnosis of urodynamic incontinence with an excellent correlation of MUCP and URP.

Creatine promotes the GABAergic phenotype in human fetal spinal cord cultures.

In the present study, we investigated the expression pattern of cytosolic brain specific-BB-CK and ubiquitous mitochondrial-creatine kinases (uMt-CK) in developing human spinal cord. Consequently, we studied the effects of creatine treatment on cultured fetal human spinal cord tissue. We found that both CK isoforms were expressed in fetal spinal cord at all time points investigated (5 to 11.5 weeks post conception) and correspondingly specific CK activity was detected. Chronic creatine exposure resulted in significantly higher densities of GABA-immunoreactive neurons in the cultures, while total neuronal cell density was not altered, suggesting a differentiation inducing mechanism of creatine supplementation. Taken together, our observations favour the view that the creatine phosphocreatine system plays an important role in the developing CNS.

Tubal sterilization: complications of laparoscopy and minilaparotomy.

OBJECTIVE: To evaluate whether intra- and post-operative morbidity varies according to the method used for female sterilization. STUDY DESIGN: The database of the Swiss obstetric study group was analyzed for a period of 9 years. After the exclusion of cases with extraneous factors that may have influenced the operative outcome, three groups of patients were identified: (1) interval laparoscopic sterilization unrelated to pregnancy (n=20,325); (2) postpartum laparoscopic sterilization (n=2233); (3) postpartum sterilization by minilaparotomy (n=5095). Intra-operative and post-operative complications were compared according to the surgical approach. RESULTS: A total of 27,653 patients were included in the study. The proportion of major complications was higher in group 3 than in group 1 (0.39% versus 0.10%, odds ratio 4.0, 95% CI 2.15-7.44, p<0.001) but not statistically different between groups 1 (0.10%) and 2 (0.18%). Minor complications were statistically significantly more frequent in group 3 (0.82%) than in group 1 (0.26%) or group 2 (0.27%). There was no case of intra-operative or post-operative death in the study population. CONCLUSION: When available, a laparoscopic approach should be chosen for female sterilization. After uneventful pregnancy course and delivery, it does not seem justified to delay the endoscopic sterilization to a later time.

PAPP-A and osteoprotegerin, together with interleukin-8 and RANTES, are elevated in the peritoneal fluid of women with endometriosis.

OBJECTIVE: The purpose of this study was to evaluate whether pregnancy-associated plasma protein A, glycodelin, osteoprotegerin, and soluble CD163 are possible peritoneal fluid markers for endometriosis and to compare them with the established chemokine markers interleukin-8 and regulated on activation, normal T-cell expressed and secreted. STUDY DESIGN: Determination of the concentrations of interleukin-8, regulated on activation, normal T-cell expressed and secreted, pregnancy-associated plasma protein A, glycodelin, CD163, osteoprotegerin, and progesterone in the peritoneal fluid collected from women undergoing laparoscopy. RESULTS: From a total of 132 women, 77 women were diagnosed with endometriosis, and 55 women were free of the disease and served as control subjects. Pregnancy-associated plasma protein A and osteoprotegerin showed significantly (P < 0.05) elevated peritoneal fluid concentrations as a function of the severity of the disease, together with interleukin-8 and regulated on activation, normal T-cell expressed and secreted (P < .001). Glycodelin and CD163 did not differ between cases and control subjects. Many of these marker concentrations were intercorrelated strongly. CONCLUSION: Pregnancy-associated plasma protein A and osteoprotegerin may play a role in the inflammation process of endometriosis, but interleukin-8 and regulated on activation, normal T-cell expressed and secreted are superior peritoneal fluid markers.

Gynaecological operations: do they improve sexual life?

Aim of the study was to determine if gynaecological operations have an effect on sexual function using the current medlined literature. We performed a Medline search using the terms "sexual life/function after operative gynaecological treatment", "sexual life/function after operations for gynaecological problems", "sexual life/function after hysterectomy", "sexual life/function, incontinence" and "sexual life/function, pelvic organ prolapse". Reviews were excluded. We divided the operations into four groups of (1) combined prolapse and incontinence operations, (2) prolapse operations only, (3) incontinence operations only and (4) hysterectomy and compared pre-to postoperative sexual outcome. Thirty-six articles including 4534 patients were identified. Only 13 studies used a validated questionnaire. The other authors used self-designed and non-validated questionnaires or orally posed questions by the examiner to determine sexual function. Prolapse operations particularly posterior repair using levator plication seem to deteriorate sexual function, incontinence procedure have some worsening effect on sexual function and hysterectomy seems to improve sexual function with no differences between subtotal or total hysterectomy. Gynaecological operations do influence sexual function. However, little validated data are available to come to this conclusion.

2,3,7,8-Tetrachlorodibenzo-p-dioxin increases glycodelin gene and protein expression in human endometrium.

CONTEXT: Glycodelin (GdA) is an immunosuppressive endometrial glycoprotein critical for embryonic implantation and pregnancy establishment. OBJECTIVE: The aim of the present study was to examine the effect of dioxin [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] on GdA production in human endometrial cells. DESIGN: Controlled endometrial explant (EE) and cell cultures were used in this study. SETTING: Work was conducted at university hospital research laboratories in Bern, Switzerland, and in San Francisco, California. PATIENTS: Ovulatory women provided endometrial biopsies in the proliferative or secretory phase. INTERVENTION(S): EEs and cells were cultured without and with TCDD. MAIN OUTCOME MEASURE(S): GdA protein and gene expression were quantified. RESULTS: A 2.5-fold increase in GdA production was demonstrated in EEs treated with 10 nm TCDD for 9 d. Fluorography revealed a 3- to 4-fold increase in new GdA biosynthesis and secretion in TCDD-treated endometrial epithelial cells. Because the action of dioxin is mediated by the aryl hydrocarbon receptor (AhR), we ascertained that primary epithelial and Ishikawa cells express AhR. Dose responses to TCDD and expressed AhR were established in transiently transfected Ishikawa cells using luciferase fusion vectors containing 1.0 kb of 5' flanking DNA relative to the GdA transcriptional start site but not when shorter promoter constructs were used. A dioxin response element was mapped to nucleotides -539 to -533 of the gene promoter and verified by site-directed mutagenesis. CONCLUSIONS: We demonstrated a direct AhR-mediated effect of dioxin on GdA gene transcription and protein secretion that might influence human female fertility.

Long-term follow-up of concurrent radiotherapy and chemotherapy for locally advanced cervical cancer: 12-Year survival after radiochemotherapy.

Recently randomized trials show an overall survival advantage of 30% for cisplatin-based chemotherapy given concurrently with radiation therapy. Current data do not allow to conclude which drugs could be best combined with cisplatin. Here we report the very long-term results of a prospective phase II trial of concurrent radiochemotherapy in advanced cancer of the cervix. Psychological impact has been evaluated with long-term survivors. Patient with squamous cell carcinoma of the cervix FIGO stage IIB, III or IVA received a concomitant chemotherapy with cisplatin, fluorouracil and mitomycin C and radiotherapy. From June 1988 to September 1990, 22 of 23 patients were eligible. The overall response rate was 82%. All 22 patients treated showed acute hematological toxicity and two patients developed severe late bowel toxicity. Ten patients (45%) were alive after a median observation time of 145.5 months. Intolerance to certain food and vaginal changes due to radiotherapy remain problematic. The lack of improvement compared to cisplatin alone and late bowel toxicity do not support the use of mitomycin C in the combination of the concurrent treatment of chemoradiation. The psychological impact of this treatment should not be minimized. Most problems tend to diminish with time with the exception of intestinal side effects and vaginal changes.

Epithelial neutrophil-activating peptide 78 concentrations are elevated in the peritoneal fluid of women with endometriosis.

OBJECTIVE: To investigate the presence of epithelial neutrophil-activating peptide 78 (ENA-78) in peritoneal fluid of women with and without endometriosis and to identify the cells that produce this inflammatory protein. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Eighteen women with and 9 women without endometriosis. MAIN OUTCOME MEASURE(S): ENA-78 protein and mRNA levels were compared among women with and without endometriosis in samples of peritoneal fluid, samples of endometriotic lesions obtained by biopsy during laparoscopy, and peritoneal macrophages. Enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and in situ hybridization methods were used. Secretion of ENA-78 protein by interleukin-1beta-stimulated endometriotic stromal cells and in the media of lipopolysaccharide-stimulated peritoneal macrophages were compared to that in unstimulated cell cultures. RESULT(S): Peritoneal fluid concentrations of ENA-78 were significantly higher in affected women than in controls. Ectopic epithelial and stromal cells and peritoneal macrophages express ENA-78 messenger RNA. Interleukin-1beta stimulation of stromal cell cultures resulted in a 23-fold increase in ENA-78 concentration, and lipopolysaccharide stimulation of peritoneal macrophages increased concentrations by 8-fold. CONCLUSION(S): Levels of ENA-78 are elevated in the peritoneal fluid of women with endometriosis. Ectopic glandular cells, ectopic stromal cells, and peritoneal macrophages express this inflammatory chemokine. Epithelial neutrophil-activating peptide 78 may play an important role in the pathogenesis of endometriosis.

Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells.

OBJECTIVE: To determine whether progestins activate vascular endothelial growth factor (VEGF) gene transcription in endometrial adenocarcinoma cells. DESIGN: In vitro study. SETTING: University reproductive biology laboratories. PATIENT(S): None. INTERVENTION(S): Ishikawa cells were transfected with VEGF promoter-luciferase reporter constructs and expression vectors encoding human progesterone receptors (hPR) A or B. The cells were treated with different progestins and antiprogestins, and luciferase activity was compared with controls. MAIN OUTCOME MEASURE(S): Three functional progesterone response elements (PREs) in the VEGF promoter were identified by electrophoretic mobility-shift assay, and different constructs were created to assess each PRE. RESULT(S): In cells expressing hPRA or B, treatment with 10 nM R5020 or 100 nM medroxyprogesterone acetate statistically significantly increased luciferase activity (3.3- to 4.8-fold). Pretreatment with 100 nM RU486 blunted the effect of 10 nM R5020, resulting only in a slight, statistically nonsignificant increase in luciferase activity (1.3- to 1.7-fold). Although three different functional PREs could be identified, no single PRE accounted for the preponderance of the luciferase activity. Full VEGF promoter activation required all three PREs. CONCLUSION(S): Progestins have a direct effect on VEGF gene transcription. However, hPR-mediated transcriptional regulation of the VEGF promoter is complex and cannot be localized to confined PRE sequences. Other response element motifs are likely to play a contributory role.

Novel placental and nonplacental serum markers in ectopic versus normal intrauterine pregnancy.

OBJECTIVE: To evaluate whether the serum concentrations of novel placental markers and nonplacental markers differ in ectopic pregnancy when compared with normal intrauterine pregnancy. DESIGN: Prospective clinical study. SETTING: University hospital. PATIENT(S): Patients with confirmed ectopic pregnancy (EP) and control population with normal intrauterine pregnancy (IUP). INTERVENTION(S): Laparoscopy. MAIN OUTCOME MEASURE(S): Serum concentrations of placental markers: pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific beta(1)-glycoprotein (SP1), human placental lactogen (HPL), and HCG; and nonplacental markers: glycodelin, vascular endothelial growth factor (VEGF), and P. RESULT(S): The multiples of median of all markers (except VEGF) were decreased in EP when compared with the control group. Conversely, the serum values of VEGF were significantly increased in EP. VEGF showed a negative correlation with HCG and SP1, but not with PAPP-A, P, or the nonplacental markers. HCG, PAPP-A, SP1, and HPL strongly correlated with each other. But, in contrast to the above, P only correlated with HCG and, in contrast to the controls, with glycodelin. The combination of three independent markers in the formula VEGF/(PAPP-A x P) was found to be largely superior to the measure of any single marker. CONCLUSION(S): The "triple marker analysis" [VEGF/(PAPP-A x P] allows a clear discrimination between normal IUP and EP.

Loss of EphB4 receptor tyrosine kinase protein expression during carcinogenesis of the human breast.

Members of the Eph family of receptor tyrosine kinase have been implicated in cell-cell communication and tissue integrity during embryogenesis. We have previously demonstrated cell type specific and hormone dependent EphB4 expression in the mouse mammary parenchyma suggesting involvement in the homeostasis of this organ. Since disruption of tissue organization is crucial for metastatic dissemination, we have investigated the expression of EphB4 during carcinogenesis of the human breast. Immunohistochemical analysis of 24 normal human breast samples and 124 consecutive breast carcinomas was correlated with tumor characteristics (stage, histology, grade, lymph node involvement) and the expression of ER, PR, Ki-67, p53 and HER2. In normal breast tissue, the EphB4 protein was expressed exclusively in parenchymal cells. Strikingly, a drastic reduction in the number of EphB4 protein expressing cells was observed in almost all invasive carcinomas analyzed, irrespective of the tumor type (p<0.0001). Furthermore, we found a highly significant correlation between EphB4 positivity and low histological grading of the tumor cells (p=0.002) suggesting that in breast cancer, EphB4 expression is not compatible with tumor progression. This raises the possibility that EphB4 could represent a potent tool for therapeutic intervention.

Urethral pressure profile: is it affected by position?

The aim of this study was to investigate the difference between sitting and standing passive urethral pressure measurements, and to determine the accuracy of urethral pressure profilometry in each position. Urethral pressure profilometry was performed in the sitting and standing position in 98 women. Stress incontinence due to urethral sphincter incompetence was demonstrated in 59 of whom 6 also had detrusor instability. The others were normal volunteers (7), women with a normal cystometrogram (23), and women with detrusor instability (9). MUCP tended to be higher in the standing than the sitting position but this did not reach statistical significance. Urethral lengthening appeared to occur on standing with a mean increase of FUL of 5 mm on standing. For both FUL and MUCP, there was a wide variation in the difference between sitting and standing values. There was poor reproducibility of measurements of MUCP and FUL in the standing position, limiting its clinical applicability. The difference between sitting and standing MUCP and FUL was not affected by age, parity, weight, height, BMI, or oestrogen status. In women with genuine stress incontinence, there was less difference between sitting and standing MUCP, but this explained only a small part of the variability. The increase in FUL in the standing position was unaffected by diagnosis.

Regulation of vascular endothelial growth factor by tamoxifen in vitro and in vivo.

OBJECTIVE: To evaluate the effects of tamoxifen on human endometrial vascular endothelial growth factor (VEGF) gene expression in vitro and in vivo. STUDY DESIGN: Ishikawa cells were transiently co-transfected with plasmids expressing human estrogen receptor (ER)-alpha or -beta and a 2.3-kb human VEGF promoter-luciferase construct. Transfected cells were treated with tamoxifen and the increase in luciferase activity was compared to controls. In addition, immunohistochemical analysis of VEGF expression in endometrial biopsies from 11 postmenopausal women receiving tamoxifen was compared to 24 postmenopausal women on no hormone replacement. RESULTS: In transfected cells expressing ERalpha, tamoxifen induced a significant VEGF promoter activation (3.2-fold, p < 0.01), whereas cells expressing ERbeta showed a 1.6-fold stimulation (p = NS). No significant differences in VEGF immunostaining were observed in tamoxifen-exposed women. CONCLUSIONS: Although tamoxifen exposure increases VEGF expression in vitro, a significant increase in VEGF expression is not apparent in endometrial biopsies of postmenopausal women treated with this drug.

Local treatment of vaginal infections of varying etiology with dequalinium chloride or povidone iodine. A randomised, double-blind, active-controlled, multicentric clinical study.

This randomised, double-blind, multicentric clinical study compared the efficacy and tolerability of the two vaginal antiseptics, 10 mg dequalinium chloride (CAS 522-51-0, Fluomycin N) and 200 mg povidone iodine (CAS 25655-41-8), in a parallel-group design. A total of 180 patients with vaginal infections of varying etiology participated in this study (bacterial vaginosis, fluor vaginalis, vulvo-vaginal candidiasis, trichomoniasis). Patients were randomly allocated to one of the two treatment groups and were treated once per day for 6 days. Control examinations took place 5 to 7 days after the end of treatment, and 3 to 4 weeks after the first control examination. The total symptoms score, a summary score for the clinical symptoms, discharge, burning, pruritus, redness of vulva/vagina, was defined as primary efficacy parameter. The treatments at the first control examination were compared in the full analysis set using the Wilcoxon-Mann-Whitney U-test, 2-sided, thereby proving equivalence of both treatments at the 5% level. Both treatments strongly improved the symptoms of vaginal infections both on short-term and long-term follow-up. Descriptive analysis of the secondary parameters, vaginal pH, degree of purity of the vaginal flora, and number of lactobacilli in the wet mounts, supported the comparable efficacy of both therapies to restore the vaginal milieu. Analysis of the diagnostic subgroups indicated that irrespective of the diagnosis, both treatments improved the efficacy criteria as observed for the entire population. The global assessment of the therapeutic efficacy by investigators and patients supported the results of the efficacy analysis with good to very good ratings in 70-90% of the cases. A good tolerability of both preparations was observed in this study with a low number of adverse events in the test group (5.8%).