The overall objectives of this investigation are to extend our evaluation of the efficacy and safety of chenodeoxycholic acid therapy for dissolving cholesterol gallstones and to initiate studies on the pathogenesis and prevention of gallstones. We propose to evaluate extension of therapy beyond 24 months in selected patients, determine a minimal effective dose of chenodeoxycholic acid, consolidate our studies of adjunctive therapy such as choline, and evaluate the efficacy and safety of this bile acid in treating biliary duct stones and preventing recurrence of stones in the gallbladder and bile ducts. Additionally, we propose to expand toxicity monitoring in patients receiving chenodeoxycholic acid. Lastly, we plan to pursue the pathogenesis of cholesterol gallstone disease by initiating relevant studies in four areas: oral contraceptive and postmenopausal estrogen treatment, pregnancy, obesity, and diet. Methods will include measurements of biliary bile acid and lipid composition, studies of bile acid kinetics, novel radioimmunoassays for serum bile acids, and cholecystography. Additionally, a historical evaluation of diet with regard to gallstone disease will be performed under double-blind conditions. BIBLIOGRAPHIC REFERENCES: Allan, R. N., Hofmann, A. F., Thistle, J. L., and Hoffman, N. E.: Absorption and Sulfation of Lithocholate in Gallstone Patients on Chenotherapy. Gastroenterology. 70:859, 1976. Thistle, J. L., Hofmann, A. F., Ott, B. J., and Yu, P. Y. S.: Gallstone Dissolution With Chenodeoxycholic Acid, 1969-1976: The Mayo Clinic Studies. Gastroenterology. 70:943, 1976.
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