Nonlinear kinetics after high‐dose omeprazole caused by saturation of genetically variable CYP2C19

K L Rost, I Roots – 1 June 1996 – Nonlinear kinetics of omeprazole and its metabolites were investigated after treatment with repeated high doses. Extensive metabolizers relating to cytochrome P450 2C19 (CYP2C19) activity received for 1 week either omeprazole at 40 mg/d (n = 14) or 60 mg/d omeprazole twice daily (n = 8). Five poor metabolizers (PMs) received 40 mg/d for 1 week. Comparison of omeprazole plasma kinetics between extensive metabolizers (EMs) and PMs after 40‐mg treatment revealed a dominant role of CYP2C19 over cytochrome P450 3A CYP3A in omeprazole metabolism.

Intensive care unit admissions with cirrhosis: Risk‐stratifying patient groups and predicting individual survival

J E Zimmerman, D P Wagner, M G Seneff, R B Becker, X Sun, W A Knaus – 1 June 1996 – Prognosis for acutely ill patients with cirrhosis is influenced by the severity of hepatic abnormalities and by dysfunction of other organ systems. The purpose of this study was to examine the usefulness of the Acute Physiology, Age, and Chronic Health Evaluation (APACHE III) prognostic system for risk‐stratifying groups of intensive care unit (ICU) patients with cirrhosis and in predicting individual survival.

Frequent expression of MUC1 apomucin on biliary epithelial cells of damaged small bile ducts in primary biliary cirrhosis and chronic viral hepatitis: An immunohistochemical study

M Sasaki, Y Nakanuma – 1 June 1996 – MUC1 apomucin is a specific target tumor antigen recognized by cytotoxic T cells in a major histocompatibility complex (MHC) unrestricted fashion in patients with pancreatic and breast cancer. This T‐cell‐mediated immune mechanism against MUC1 apomucin expressing cells has not been evaluated in nonneoplastic immune‐mediated diseases. Therefore, we immunohistochemically surveyed the expression of MUC1 apomucin on biliary epithelial cells of small bile ducts in various hepatobiliary diseases, including primary biliary cirrhosis (PBC).

Ursodeoxycholic acid or clofibrate in the treatment of non‐alcohol‐induced steatohepatitis: A pilot study

J Laurin, K D Lindor, J S Crippin, A Gossard, G J Gores, J Ludwig, J Rakela, D B McGill – 1 June 1996 – Non‐alcohol‐induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH.

Gene therapy for α‐fetoprotein‐producing human hepatoma cells by adenovirus‐mediated transfer of the herpes simplex virus thymidine kinase gene

F Kanai, Y Shiratori, Y Yoshida, H Wakimoto, H Hamada, Y Kanegae, I Saito, H Nakabayashi, T Tamaoki, T Tanaka, K Lan, N Kato, S Shiina, M Omata – 1 June 1996 – We have developed a recombinant replication‐defective adenovirus containing human α‐fetoprotein (AFP) promoter/enhancer to direct cell type‐specific expression of the herpes simplex virus thymidine kinase (HSVtk) gene to AFP‐producing hepatocellular carcinoma (HCC) cells.

Biosynthesis and degradation of hyaluronan by nonparenchymal liver cells during liver regeneration

D Vrochides, V Papanikolaou, H Pertoft, A A Antoniades, P Heldin – 1 June 1996 – Hepatic stellate cells (HSC) and endothelial cells of the liver sinusoids synthesize and degrade hyaluronan, respectively. The roles of these cell types in the biosynthesis and degradation of hyaluronan were studied during regeneration following partial hepatectomy. Pure cultures of HSC and liver endothelial cells (LEC) were obtained from regenerating liver at different stages using a Nycodenz gradient followed by discontinuous Percoll gradient.

Thalidomide inhibits tumor necrosis factor α, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal‐hypertensive rats

J C Lopez‐Talavera, G Cadelina, J Olchowski, W Merrill, R J Groszmann – 1 June 1996 – A hyperdynamic circulatory state frequently is observed in portal hypertension with liver failure or extensive portal‐systemic shunting. Tumor necrosis factor α (TNF) causes marked hypotension in mammals by inducing nitric oxide synthesis and has been shown to play a role in the development of the hemodynamic changes observed in portal hypertension. Thalidomide selectively inhibits TNF production by enhancing messenger RNA degradation.

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