Pharmacokinetic and pharmacodynamic modelling of metoprolol in rabbits with liver failure

The pharmacokinetic and pharmacodynamic profiles of metoprolol were studied in adult male rabbits given 3.2 mg/kg i.v. before and during liver failure. The partition of metoprolol between blood cells and plasma averaged 1.14 in both conditions. Plasma protein binding, concentration-independent, was 32% and 17% in normal and pathological status, respectively. With normal liver function the terminal elimination half-life for the drug was 0.54-0.96 h, rising to 1.0-2.1 h in liver failure. Differences of the same order were observed for total plasma drug clearance (average 3.7 vs 1.5 1/h/kg), MRT (0.77 vs 1.92 h), AUC (0.9 vs 2.2 mg h/l) and k10 (3.17 vs 1.80 h-1). Liver impairment did not affect the volume of distribution of the central compartment, the steady-state volume of distribution and the other intercompartmental rate constants. Although metoprolol was eliminated in the urine, the amount excreted was low (1.5% of the administered dose) in both conditions. The pharmacokinetic model was extended by an 'effect compartment', which has no influence on the predetermined mass of drug in the body, to analyse the relationship between heart rate fall and changes in metoprolol plasma concentrations. After drug administration, heart rate fell rapidly about 90 beats in both states. The mean unbound plasma concentration producing 50% of this reduction was double during liver failure compared to normal condition (0.03 vs 0.07 mg/l), but the temporal aspects of drug equilibration with site of action were similar.     

Percutaneous Alcohol Sclerotherapy of Simple Hepatic Cysts. Results From a Multicentre Survey in Italy

The increased use of Ultrasonography (US) has led to increased detection of simple hepatic cysts. For symptomatic cysts treatment is necessary. Until some years ago surgery was the only therapy. We have treated a large number of patients with Percutaneous Alcohol Sclerotherapy (PAS) and evaluated retrospectively the efficacy of this approach.Data on 21 patients with symptomatic simple hepatic cysts were reviewed retrospectively. Cysts had a mean diameter of 9 cm (range: 7–15 cm). PAS was always performed under local anesthesia and US guidance. 25% of the volume was replaced with 95% ethanol and then completely aspirated after 20–30 minutes.No complications or deaths occurred. In all patients symptoms disappeared after treatment. In 15 out of 21 cases there was no evidence of residual cyst on US, computed tomography (CT) or magnetic resonance (MRI). In 6 patients with shorter follow-up, cysts showed a mean reduction in diameter of 50%. The mean follow-up was 18 months (range 6–60 months).We conclude that PAS is easy with low risk for the patients and with good long-term results; it should therefore become the procedure of choice for simple hepatic cysts.     

Natural killer activity in patients with acute viral hepatitis.

Using the natural killer (NK) sensitive K562 cell line, enhanced NK cell cytotoxicity was demonstrable early in the course of acute hepatitis B while normal values were obtained in patients studied during convalescence. No evidence of enhanced NK activity was instead obtained in the course of acute non-A, non-B hepatitis. Serum levels of alpha-interferon, as determined by radioimmunoassay (RIA), were significantly increased in patients with acute hepatitis B showing enhanced NK cell activity but not in those with acute non-A, non-B hepatitis and normal NK cell activity. These results suggest that natural cytotoxicity may play a role early in the course of acute hepatitis type B, before antigen-specific T lymphocytes become fully operative.     

Face-selective processing and the effect of pleasant and unpleasant emotional expressions on ERP correlates.

Previous studies have revealed that decoding of facial-expressions starts very early in the brain ( approximately 180 ms post-stimulus) and might be processed separately from the basic stage of face perception. In order to explore brain potentials (ERPs) related to decoding of facial-expressions and the effect of emotional valence of the stimulus, we analyzed 18 normal subjects. Faces with five basic emotional expressions (fear, anger, surprise, happiness, sadness) and neutral stimulus were presented in random order. The results demonstrated that an emotional face elicited a negative peak at approximately 230 ms (N230), distributed mainly over the posterior site for each emotion. The electrophysiological activity observed may represent specific cognitive processing underlying the decoding of emotional facial-expressions. Nevertheless, differences in peak amplitude were observed for high-arousal negative expressions compared with positive (happiness) and low-arousal expressions (sadness). N230 amplitude increased in response to anger, fear and surprise, suggesting that subjects' ERP variations are affected by experienced emotional intensity, related to arousal and unpleasant value of the stimulus.     

Post bending of the polypropylene flexible stent in mitral Hancock bioprostheses

The occurrence of stent post deformity was investigated in 38 consecutive, polypropylene flexible-stented Hancock porcine bioprostheses (PB) recovered from the mitral position because of early postoperative death or late tissue failure. The degree of deformity was assessed for each explant by calculating the triangular area obtained by projecting the apex of the stent posts on a plane and comparing it with the same area calculated for unimplanted PBs of comparable size. A significant stent deformity (reduction of the triangular area greater than 40%) was observed only in 6 PBs explanted because of tissue failure after a mean function time of 69.6 +/- 28 months. In these PBs, scanning electron microscopy of the bare surface of the stent at the point of maximal flexion showed cracks 0.7-1 microns large, which represent the morphological substrate of the so-called "creep" of polypropylene. Inward stent post bending may occur after implantation in mitral PBs and when severe, it corresponds to a definite ultrastructural plastic deformity of polypropylene.