Hepatic expression of MxA and OAS1 in an ex vivo liver slice assay independently predicts treatment outcomes in chronic hepatitis C.

Antiviral effect of interferon is mediated by the expression of interferon-stimulated genes (ISGs). However, because of the difficulty in obtaining paired liver biopsies before and after interferon treatment, the key ISGs expressed in human hepatocytes and responsible for interferon-based antiviral activities in chronic hepatitis C remain illusive. Prior to a standard course of peginterferon plus ribavirin therapy, 104 patients underwent a liver biopsy. A small piece of the liver biopsy sample from each patient was submitted for ex vivo tissue culture in the presence or absence of interferon. Hepatic expression of 8 ISGs was detected by RT-PCR. The ISG expression patterns and clinicopathological variables were correlated with subsequent treatment outcomes. Multivariate logistic regression analysis showed that hepatic MxA expression (P = 0.008) and leucocyte count (P = 0.040) independently predicted the end of therapeutic virological response, while hepatic OAS1 expression (P = 0.003), genotype 1 (P = 0.002), HCV-RNA level (P = 0.007), AST/ALT ratio (P = 0.004) and leucocyte count (P = 0.034) independently predicted the sustained virological response. Immunohistochemistry analysis showed that interferon-induced OAS1 expression localized to the hepatocytes. In conclusion, hepatic MxA and OAS1 expression predicted, respectively, the end of therapeutic and sustained virological responses in interferon-based treatment of chronic hepatitis C.

Pneumocephalus and respiratory depression after accidental dural puncture during epidural analgesia--a case report.

A case of pneumocephalus and respiratory depression after dural puncture during lumbar epidural analgesia is reported. The loss of resistance to air technique was employed to identify the epidural space. Severe respiratory depression and stuporous consciousness developed one hour after a bolus of 2 mg morphine was given epidurally at the end of operation. With computerized tomographic brain scanning and continuous observation of clinical course, the neurologic symptoms were thought to be a mixed complication of pneumocephalus and possible intrathecal morphine overdose. We suggest that in order to avoid iatrogenic pneumocephalus by inadvertent dural puncture in the attempt to identify the epidural space the use of the loss of resistance to normal saline technique or the hanging-drop technique is more reliable than the loss of resistance to air technique. A small test dose prior to a full dose is given and should not be omitted to further confirm the proper placement of the epidural catheter during epidural analgesia.

Priming reversal of profound atracurium blockade by edrophonium and neostigmine.

Accelerated reversal of moderate neuromuscular blockade has been reported to be effective by giving anticholinesterase in divided doses (priming reversal). To evaluate its effectiveness in profound blockade, forty ASA physical status I or II patients were studied. After receiving 0.5mg/kg of atracurium during N2O-O2-halothane anesthesia, they were reversed at 5% spontaneous recovery of first twitch height (T1) measured by train-of-four (TOF) stimulation. Edrophonium 1mg/kg was administered intravenously either in a single bolus dose (Group I, n = 10) or in an initial priming dose of 0.2mg/kg followed one minute later by 0.8mg/kg (Group II, n = 10). Neostigmine 0.05mg/kg was administered in a single bolus dose (Group III, n = 10) or in divided priming dose of 0.01 mg/kg followed one minute later by 0.04mg/kg (Group IV, n = 10). The recovery time from the first injection of the reversal agents until the TOF ratio reached 75% was significantly longer (p < 0.05) in Group III (681.5 +/- 77.5 sec) compared to Groups I, II, and IV (451.3 +/- 72.3 sec, 470.6 +/- 39.8 sec, and 448.1 +/- 42.5 sec, respectively; no statistical difference among these three groups). It is concluded that priming reversal by neostigmine, but not edrophonium, produced a significantly faster recovery of profound atracurium blockade. Using the priming method, neostigmine may reach a similar recovery time as edrophonium in profound blockade under equipotent doses.