Genetic heterogeneity of the NS3 protease gene in hepatitis C virus genotype 1 from untreated infected patients

NS3 protease is essential for hepatitis C Virus (HCV) replication, and is one of the most promising targets for specific anti-HCV therapy. Its natural polymorphism has not been studied at the quasispecies level. In the present work, the genetic heterogeneity of the NS3 protease gene was analyzed in 17 HCV genotype 1 (5 subtypes 1a and 12 subtypes 1b) samples collected from infected patients before anti-viral therapy. A total of 294 clones were sequenced. Although the protease NS3 is considered to be one of the less variable genes in the HCV genome, variability of both nucleotide and amino acid sequences was found. In variants belonging to 1a and 1b subtypes, 224 and 267 of 543 positions showed one or more nucleotide substitutions, respectively. Forty and 74 of the 181 NS3 amino acid positions showed at least one mutation in HCV-1a and HCV-1b isolates, respectively. Most substitutions were conservative. This substantial polymorphism of the NS3 protease produced by HCV-1a and HCV-1b suggests that, despite the numerous functional and structural constraints, the enzyme is sufficiently flexible to tolerate substitutions.     

Demand for care in traumatic war neuroses

Psychiatrists who must take care of patients suffering of Post Traumatic Stress Disorders are often surprised in front of the strength of repetition of the related frightful experience. Therapeutics methods which are more often used (Abreaction and Narcissism reconstruction by varied technics) have showed their limits. Leaning on their experience and referring to psycho-analytic teaching, the authors show the interest of the individual psychotherapy. They propose not to be strongly affected by the massive aspect to the "trauma" and to permit as far as possible the installation of the transfer.     

Does halothane or isoflurane affect hypoxic and post‐hypoxic vascular response in rabbit aorta?

BACKGROUND: Halothane and isoflurane affect differently endothelium-dependent and -independent vasorelaxation at 95% O2. In addition, hypoxic vascular response might involve endothelium-dependent and -independent mechanisms. Therefore, we investigated, in rabbit aortic rings, 1) the influence of halothane and isoflurane on vasodilation at 95% O2 and on hypoxic-induced vasorelaxation at 0% O2 and 2) the influence of halothane and isoflurane on endothelium-dependent and -independent post-hypoxic vascular response. METHODS: Endothelium-intact and endothelium-denuded rabbit aortic rings were used. Phenylephrine precontracted rings were exposed, at 95% O2, to acetylcholine (ACh, 10(-9) to 10(-4) M) or sodium nitroprusside (SNP, 10(-9) to 10(-4) M) in the presence or absence of anaesthetic at 1 or 2 MAC. Precontracted rings were also exposed to an acute reduction in O2 from 95% to 0% followed by an acute reoxygenation with 95% O2 in the absence or presence of anaesthetic at 1 or 2 MAC. RESULTS: At 95% O2, halothane decreased endothelium-dependent relaxation to ACh, while endothelium-independent relaxation to SNP was decreased only at 2 MAC. Isoflurane did not modify ACh- or SNP-induced relaxation. At 0% O2, neither halothane nor isoflurane altered the hypoxic vascular relaxation. Post-hypoxic response was not changed either. CONCLUSION: Our results indicate that halothane and isoflurane do not alter vascular hypoxic response in conductance arteries.     

Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): a propensity-matched analysis

Background

A greater incidence of persistent pain after inguinal herniorrhaphy is suspected with the open mesh procedure than with laparoscopy (transabdominal preperitoneal), but the involvement of neuropathy needs to be clarified.

Methods

We examined the cumulative incidence of neuropathic persistent pain, defined as self-report of pain at the surgical site with neuropathic aspects, within 6 months after surgery in 2 prospective subcohorts of a multicentre study. We compared open mesh with laparoscopy using different analysis, including a propensity-matched analysis with the propensity score built from a multivariable analysis using a generalized linear model.

Results

Considering the full patient sample (242 open mesh v. 126 laparoscopy), the raw odds ratio for neuropathic persistent pain after inguinal herniorrhaphy was 4.3. It reached 6.8 with the propensity-matched analysis conducted on pooled subgroups of 194 patients undergoing open mesh and 125 undergoing laparoscopy (95% confidence interval 1.5–30.4, p = 0.012). A risk factor analysis of these pooled subgroups revealed that history of peripheral neuropathy was an independent risk factor for persistent neuropathic pain, while older age was protective.

Conclusion

We found a greater risk of persistent pain with open mesh than with laparoscopy that may be explained by direct or indirect lesion of nerve terminations. Strategies to identify and preserve nerve terminations with the open mesh procedure are needed.