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7 9) Reichen J, Paumgartner G: Relationship be- tween bile flow and Na+, K+-Adenosinetriphos- phatase in liver plasma membranes enriched in bile canaliculi. J Clin Invest 60: , ) Schaffner F, Popper H: Cholestasis is the result of hypoactive hypertrophic smooth endoplasmic reticulum in the hepatocyte. Lancet II: , ) Nair PP, Garcialilis C, Mendeloff AI: Effect of 1) Aach RD: Corticosteroid and bilirubin metabolism. Gastroenterology 56: , ) Adachi Y, Yamamoto T: Influence of drugs and chemicals upon hepatic enzymes and proteins. II. The effects of various barbiturates on the induction and reduction of hepatic cytoplasmic organic anion-binding proteins. Gastroenterologia Jap 11: 23-30, ) Thaler MM: Effects of barbiturate on biliary excretion in intrahepatic biliary atresia. Pediat Res: 355, ) Sharp HL, Mirkin BL: Effect of phenobarbital on hyperbilirubinemia, bile acid metabolism, and microsomal enzyme activity in chronic intrahepatic cholestasis of childhood. J Pediat 81: , ) Stiehl A, Thaler MM, Admirand WH: The effects of phenobarbital bilirubin in patients with intrahepatic on bile salts and and extrahepatic cholestasis. N Eng J Med 286: , ) Stiehl A, Thaler MM, Admirand WH: Effects of phenobarbital on bile salt metabolism in cholestasis due to intrahepatic bile duct hypoplasia. Pediat 51: , ) Bloomer JR, Boyer JL: Phenobarbital effects in cholestatic liver disease. Ann Intern Med 82: , ) Simon FR, Sutherland E, Accatino L: Stimulation of hepatic sodium and potassium-activated adenosine triphosphatase activity by phenobarbital. J Clin Invest 59: , 1977 lithocholic acid and antibiotics on tissue bile acids in the rat. J Nutr 100: , ) Javitt NB: Bile salt regulation of hepatic excretory function. Gastroenterology 56: , ) Boyer JL, Layden TJ: Mechanisms of cholestasis-taurolithocholates alters canalicular membrane composition, structure and permeability. In: Membrane alterations as basis of liver injury. Edited by Popper H, Bianchi L. MTP, Landcaster, 1977, p ) Frohling W, Stiehl A: Bile salt glucuronidesidentification and quantitative analysis in the urine of patients with cholestasis. Eur J Clin Invest 6: 67-74, ) Stiehl A, Becker M, Czygan P, et al: Bile acids and their sulphated and glucuronidated derivatives in bile, plasma, and urine of children with intrahepatic cholestasis-effects of phenobarbital treatment. Eur J Clin Invest 10: , 1980

8 The effect of phenobarbital on bile acids and bilirubin in two patients with prolonged severe intrahepatic cholestasis Hironao KOMATSU, Satoshi MONNO, Yukio GIBO, Yoshihiro AKAHANE, Kendo KIOSAWA, Atsuo NAGATA and Seiichi FURUTA* We reported two patients of prolonged severe intrahepatic cholestasis who showed a rapid response to the phenobarbital (PB) administration, followed with the disappearance of jaundice. Case 1, 27-year-old male, and case 2, 22-year-old female, were admitted to our department because of severe jaundice and pruritus of long duration. Glucocorticoid therapy for 100 and 190 days was not effective in both cases. In case 1, after three months of PB (3mg per kg of body weight per day) treatment, total serum bile acids concentration (TBA) decreased from 140ƒÊMol/l to 7.9ƒÊMol/l and total serum bilirubin level (T. Bil) from 30mg/dl to 0.7mg/dl. In case 2, after about fifty days of PB (2mg per kg of body weight per day) TAB decreased from 270ƒÊMol/l to 14.6ƒÊMol/l and T. Bil from 35.8mg/dl to 1.8mg/dl. PB was very effective in relieving the pruritus and decreasing the jaundice. The mechanism of the therapeutic effect of PB on prolonged intrahepatic cholestasis was discussed.

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