Laparoscopic repair of vaginal vault prolapse by lateral suspension with mesh

Background: To evaluate the long-term outcomes of laparoscopic lateral suspension using mesh reinforcement for symptomatic posthysterectomy vaginal vault prolapse. Materials and methods: We analyzed in a prospective cohort study all the women treated by laparoscopic lateral suspension with mesh for symptomatic vaginal vault prolapse between January 2004 and September 2010. In this procedure, the mesh is laterally suspended to the abdominal wall, posterior to the anterior superior iliac spine. We performed systematic follow-up examinations at 4weeks, 6months and yearly postoperatively. Clinical evaluation of pelvic organ support was assessed by the pelvic organ prolapse quantification (POP-Q) grading system. Main outcome measures were recurrence rate, reoperation rate for symptomatic recurrence or de novo prolapse, mesh erosion rate, reoperation rate for mesh erosion, total reoperation rate. Observations and results: Of the 73 patients seen at a mean 17.5months follow-up, recurrent vaginal vault prolapse was registered in only one woman (success rate of 98.6%). When considering all vaginal sites, we observed a total of 13 patients with recurrent or de novo prolapse (17.8%). The non-previously treated posterior compartment was involved in eight cases (new appearance rate of 11%). Of these 13 women, only 6 were symptomatic, requiring surgical management (reoperation rate for genital prolapse of 8.2%). Four patients presented with mesh erosion into the vagina (5.5%). Two required partial vaginal excision of the mesh in the operating room (2.7%). There were no mesh-related infections. The total reoperation rate was 11%. Conclusion: Laparoscopic lateral suspension with mesh interposition is a safe and effective technique for the treatment of vaginal vault prolapse. This approach represents an alternative procedure to the laparoscopic sacrocolpopex

Virology and cell biology of the hepatitis C virus life cycle: an update.

Affiliations ECOFECTInternational audienceHepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways

The Hepatitis C Virus Glycan Shield and Evasion of the Humoral Immune Response

Despite the induction of effective immune responses, 80% of hepatitis C virus (HCV)-infected individuals progress from acute to chronic hepatitis. In contrast to the cellular immune response, the role of the humoral immune response in HCV clearance is still subject to debate. Indeed, HCV escapes neutralizing antibodies in chronically infected patients and reinfection has been described in human and chimpanzee. Studies of antibody-mediated HCV neutralization have long been hampered by the lack of cell-culture-derived virus and the absence of a small animal model. However, the development of surrogate models and recent progress in HCV propagation in vitro now enable robust neutralization assays to be performed. These advances are beginning to shed some light on the mechanisms of HCV neutralization. This review summarizes the current state of knowledge of the viral targets of anti-HCV-neutralizing antibodies and the mechanisms that enable HCV to evade the humoral immune response. The recent description of the HCV glycan shield that reduces the immunogenicity of envelope proteins and masks conserved neutralizing epitopes at their surface constitutes the major focus of this review

Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies

Last Stop Before Exit – Hepatitis C Assembly and Release as Antiviral Drug Targets

Chronic Hepatitis C infection is a global health problem. While primary infection is often inapparent, it becomes chronic in most cases. Chronic infection with Hepatitis C virus (HCV) frequently leads to liver cirrhosis or liver cancer. Consequently, HCV infection is one of the leading causes for liver transplantation in industrialized countries. Current treatment is not HCV specific and is only effective in about half of the infected patients. This situation underlines the need for new antivirals against HCV. To develop new and more efficient drugs, it is essential to specifically target the different steps of the viral life cycle. Of those steps, the targeting of HCV assembly has the potential to abolish virus production. This review summarizes the advances in our understanding of HCV particle assembly and the identification of new antiviral targets of potential interest in this late step of the HCV life cycle

endemic to semi-dry forests in La Réunion

Unexpected populations of Hymenophyllaceae ferns were observed and collected at low to middle elevations as epilithic in wet ravines within the semi-dry forest in La Réunion Island. These populations would represent lowland ecotypes of the montane Crepidomanes inopinatum, which is usually restricted to humid rainforests at higher elevations. Because of this unexpected habitat and the dwarfed size of the specimens by comparison to typical populations, we thus describe a new variety for the island. Résumé Des populations inattendues de fougères Hymenophyllaceae ont été observées et collectées à basses et moyennes altitudes en épilithes dans des ravines humides au sein de la forêt semi-sèche à la Réunion. Ces populations représenteraient des écotypes de basses altitudes de l’espèce de montagne Crepidomanes inopinatum normalement restreinte aux forêts humides d’altitude. Compte-tenu de cet habitat inattendu et de la taille naine des individus comparativement à celle des populations types, nous proposons donc de décrire une nouvelle variété pour l’île. Filmy ferns (Hymenophyllaceae) are typical hygrophilous ferns that can only grow in the wettest places. The one-cell thick lamina and the absence of cuticle do not allow these plants to endure a long period of drought, even if many species are poikilohydric but only for a relative short period (see Dubuisson et al. 2013a). In the western Indian Ocea

Comprehensive linker-scanning mutagenesis of the hepatitis C virus E1 and E2 envelope glycoproteins reveals new structure–function relationships

Despite extensive research, many details about the structure and functions of hepatitis C virus (HCV) glycoproteins E1 and E2 are not fully understood, and their crystal structure remains to be determined. We applied linker-scanning mutagenesis to generate a panel of 34 mutants, each containing an insertion of 5 aa at a random position within the E1E2 sequence. The mutated glycoproteins were analysed by using a range of assays to identify regions critical for maintaining protein conformation, E1E2 complex assembly, CD81 receptor binding, membrane fusion and infectivity. The results, while supporting previously published data, provide several interesting new findings. Firstly, insertion at amino acid 587 or 596 reduced E1E2 heterodimerization without affecting reactivity with some conformation-sensitive mAbs or with CD81, thus implicating these residues in glycoprotein assembly. Secondly, insertions within a conserved region of E2, between amino acid residues 611 and 631, severely disrupted protein conformation and abrogated binding of all conformation-sensitive antibodies, suggesting that the structural integrity of this region is critical for the correct folding of E2. Thirdly, an insertion at Leu-682 specifically affected membrane fusion, providing direct evidence that the membrane-proximal ‘stem’ of E2 is involved in the fusion mechanism. Overall, our results show that the HCV glycoproteins generally do not tolerate insertions and that there are a very limited number of sites that can be changed without dramatic loss of function. Nevertheless, we identified two E2 insertion mutants, at amino acid residues 408 and 577, that were infectious in the murine leukemia virus-based HCV pseudoparticle system

Incidence and risk factors for reoperation of surgically treated pelvic organ prolapse

Introduction and hypothesis: The objective of our study was to estimate the incidence and to identify the risk factors for reoperation of surgically treated pelvic organ prolapse (POP). Methods: We conducted a nested case-control study among 1,811 women who underwent POP surgery from January 1988 to June 2007. Cases (n = 102) were women who required reoperation for POP following the first intervention through December 2008. Controls (n = 226) were women randomly selected from the same cohort who did not require reoperation. Results: The incidence of POP reoperation was 5.1 per 1,000 women-years. The cumulative incidence was 5.6%. Risk factors included preoperative prolapse in more than two vaginal compartments (adjusted OR 5.2; 95% CI 2.8-9.7), history of surgery for POP and/or urinary incontinence (adjusted OR 3.2; 95% CI 1.5-7.1), and sexual activity (adjusted OR 2.0; 95% CI 1.0-3.7). Conclusions: The risk of POP reoperation is relatively low and is associated with preexisting weakness of pelvic tissue

Incidence rate and risk factors for vaginal vault prolapse repair after hysterectomy

Our objective was to estimate the incidence and identify the risk factors for vaginal vault prolapse repair after hysterectomy. We conducted a case control study among 6,214 women who underwent hysterectomy from 1982 to 2002. Cases (n = 32) were women who required vaginal vault suspension following the hysterectomy through December 2005. Controls (n = 236) were women, randomly selected from the same cohort, who did not require pelvic organ prolapse surgery. The incidence of vaginal vault prolapse repair was 0.36 per 1,000 women-years. The cumulative incidence was 0.5%. Risk factors included preoperative prolapse (odds ratio (OR) 6.6; 95% confidence interval (CI) 1.5-28.4) and sexual activity (OR 1.3; 95% CI 1.0-1.5). Vaginal hysterectomy was not a risk factor when preoperative prolapse was taken into account (OR 0.9; 95% CI 0.5-1.8).Vaginal vault prolapse repair after hysterectomy is an infrequent event and is due to preexisting weakness of pelvic tissue