The Sunnybrook Gallstone Study was a randomized, double-blind, controlled trial of chenodeoxycholic acid treatment over 2 years in 160 patients with radiolucent gallstones. Sixty-four patients received 750 mg daily, 53 received 375 mg daily and 43 received placebo. Total dissolution of gallstones occurred in 10.9% of patients on 750 mg daily, 13.2% of those on 375 mg daily and in no patient on placebo. The drug was tolerated well. Diarrhea severe enough to cause withdrawal from the study occurred in two patients. No patient developed clinically significant hepatotoxicity. Serum cholesterol rose 10% or more above baseline after 2 years in 33% of patients treated with chenodeoxycholic acid and in 30% of those on placebo. Cholecystectomy was performed in 10.9% of patients on 750 mg daily, 17% on 375 mg daily and 13.6% on placebo. Chenodeoxycholic acid given at these doses dissolved radiolucent gallstones safely but the efficacy was limited.

Adult↗

PubMedDate not supplied

Disposition of intravenous propylthiouracil.

Propylthiouracil was administered to 10 healty, male volunteers by a short intravenous infusion. Plasma and urinary drug concentrations were determined by a specific high-performance liquid chromatography assay, and protein binding was determined by equilibrium dialysis. After infusion, the plasma concentrations declined biexponentially, and the following median parameters (and ranges) were determined: clearance 273.5 ml/min (159.5-377.8 ml/min); free drug clearance, 1537.7 ml/min (985.9-1927.3 ml/min); apparent volume of distribution, 28.0 liters (22.7-44.4 liters); apparent elimination half-life, 1.28 hr (0.88-2.05 hr); k21, 3.12 hr-1 (1.06-5.36 hr-1): alpha 7.34 hr-1 (1.94-25.03 hr-1): Vc 9.40 liters (5.16-18.58 liters). In urine, only 1.28 per cent (0.03-2.01 per cent) of the administered dose was recovered over 24 hours as unchanged drug. The ratio (1.2 per cent) of urinary clearance (3.2 ml/min) to plasma clearance is far less (P less than 0.001) than the free fraction in plasma (median 18.2 percent, range 16.2-20.2 per cent) and this suggests that there is significant renal tubular reabsorption of propylthiouracil. In healthy subjects, both intraindividual and interindividual variation of protein binding is modest, and free drug clearance can be predicted from total drug clearance (y =- 257.6 + 4.56x, r = 0.95, P less than 0.001).

Adult↗

PubMedDate not supplied

Autoimmune hepatitis.

Autoimmune hepatitis can present as either acute or chronic disease in children. Clinical and laboratory features, including association with extrahepatic autoimmune syndromes and prompt response to immunosuppressive treatment, circulating autoantibodies and hypergammaglobulinemia, suggest an immune etiology. However, the disease mechanism remains uncertain. Different types of autoimmune hepatitis are defined on the basis of which autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases which may be clinically similar to autoimmune hepatitis must be excluded before the diagnosis of autoimmune hepatitis is established: Wilson's disease, primary sclerosing cholangitis, chronic hepatitis B or C, and drug-induced liver disease are among the most important entities. Corticosteroids alone or with azathioprine constitute the usual treatment for autoimmune hepatitis. Although some children achieve a complete remission, or even recovery, and can stop immunosuppressive treatment, others required low-dose prednisone treatment indefinitely.

Adrenal Cortex Hormones↗