Cisplatin is a highly effective chemotherapeutic agent but displays significant ototoxic side effects. The most prominent change seen in the cochlea after cisplatin administration consists of loss of outer hair cells. Several mechanisms are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to guanine bases on DNA and the formation of inter- and intra-strand chain cross-linking, generation of reactive oxygen species (ROS) with increased lipid peroxidation and Ca(2+) influx and, finally, inflammation mediated by cisplatin. The aim of the present review is to analyze the role of ROS in the mechanisms causing cisplatin-mediated apoptosis in the inner ear and the contribution of the different pathways involved, emphasizing the main strategies to blockade events leading to apoptosis of cochlear cells.

Background and purpose: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg -1 body weight). Experimental approach: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. Key results: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. Conclusions and implications: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.

Sudden deafness constitutes a diagnostic challenge. Classically, 2 causes, viral and vascular, are considered in the origin of idiopathic sudden hearing loss. More recently added to the list of possibilities are rupture of the membranous labyrinth and immune-mediated sensorineural hearing loss. The latter can be either primary and localized to the inner ear or, in perhaps fewer than one third of cases, secondary to generalized systemic autoimmune disease. The purpose of the present review is to define immune-mediated sudden sensorineural hearing loss as a distinctive entity, on the basis of clinical, immunologic, and pathological findings, and suggest a profile of the typical patient.

Aim: To study peri-surgical complications after cure of genital prolapse by vaginal route using interposition of synthetic prostheses Gynemesh Prolene Soft (Gynecare) following the Trans Vaginal Mesh (TVM) technique. Methods: The present retrospective multicentered study comprised 684 patients who underwent surgery at seven French centers between October 2002 and December 2004. All patients had a genital prolapse Ն3 (C3/H3/E3/R3) according to International continence society (ICS) classification. According to each case, prosthetic interposition was total, or anterior only or posterior only. Patients were systematically seen 6 weeks, 3 months and 6 months after surgery. Multivaried statistical analysis followed a model of logistic regression applied to each post-surgical complication. Results: The mean age of patients was 63.5 years (30-94). The mean follow-up period was 3.6 months. 84.3% of patients were post-menopause, 24.3% had hysterectomy, 16.7% previous cure of prolapse, and 11.1% cure of stress urinary incontinence (SUI). During the procedure, hysterectomy was combined in 50.3% of cases, cervix amputation in 1.5%, and cure of SUI in 40.9%. 15.8% were treated for a cystocele only. 14.8% had only a rectocele +/-elytrocele and 69.4% had a prolapse touching both compartments, anterior and posterior. In peri-surgical complications, (2%) were five bladder wounds (0.7%), one rectal wound (0.15%) and seven hemorrhages greater that 200 mL (1%). Among early post-surgical complications (during the first month after surgery) (2.8%) were two pelvic abscesses (0.29%), 13 pelvic hematomas (1.9%), one pelvic cellulitis (0.15%), two vesicovaginal fistulas and one rectovaginal fistula (0.15%). Among late post-surgical complications (33.6%) there were 77 granulomas or prosthetic expositions (11.3% [6.7% in the vaginal anterior wall, 2.1% in the vaginal posterior wall and 4.8% in the fornix]), 80 prosthetic retractions (11.7%), 36 relapse of prolapse (6.9%) and 37 SUI de novo (5.4%). Multivaried analysis shows that previous history of hysterectomy or placing of an isolated anterior prosthesis increase the risk of peri-surgical complication; preserved uterus and isolated posterior prosthesis lessen the risk of granulomas and prosthetic retractions; and association of a Richter's intervention increases the rate of prosthetic retractions. Conclusion: Cure of genital prolapse with synthetic prostheses interposed by vaginal route is now reliable and can be reproduced with a low rate of peri-and early post-surgical complications. However, our study shows a certain number of late post-surgical complications after insertion of strengthening synthetic vaginal implants (prosthetic expositions and prosthetic retractions). These retrospective results will soon be compared to a prospective study.

When comparing different studies the hearing thresholds were found to be similar. Therefore, it would be possible to establish international standard thresholds.