Biomedical subjects

B J Pearlman

Publications and source records attributed to B J Pearlman.

5 recordsLinked to original sources

PubMed1981

Sulfation of lithocholate as a possible modifier of chenodeoxycholic acid-induced elevations of serum transaminase in patients with gallstones.

Chenodeoxycholic acid (CDC), through its metabolite, lithocholic acid (LC), is hepatotoxic in certain species. The cause of elevations of serum transaminase in 25% of humans ingesting CDC, however, is unknown, but also may be due to LC. Because efficient hepatic sulfation of LC may protect against hepatic injury, the aim of this study was to determine if sulfation of LC might modify CDC-induced elevations of transaminase. Pretreatment sulfation fraction (SF) was estimated in 63 randomly selected patients with gallstones in a double-blind randomized trial of CDC, 750 mg/d, 375 mg/d, or placebo; in 27 of these, SF was repeated at 1 or 2 yr. In four other patients, the SF was measured at 2 yr only. Serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase were determined monthly for 3 mo and then every 3 or 4 mo; an elevation of transaminase was defined as > 150% of the normal upper limit in asymptomatic patients. 10 muCi of (3)H-glyco-LC (sp act 84 mCi/mol) was ingested 10-12 h before fasting duodenal biliary drainage. Bile acids in bile were separated by thin-layer chromatography. The SF was estimated as a percentage of total radioactivity (scintillation counting) in sulfated glyco-LC. The standard deviation for replicate SF determinations (n = 311) was 2.1% The pretreatment SF (mean 60.7+/-1.7 SEM) correlated inversely with age (r = 0.336, P < 0.005) and directly with the obesity index (r = 0.495, P > 0.001), but was independent of sex. The SF, remeasured at 1 or 2 yr, did not change significantly with time or CDC. Among CDC-treated patients, elevations of transaminase occurred in 75% of patients with a SF < 45% vs. 11% with a SF > 45% (P < 0.001). In conclusion, a SF < 45% occurred in patients with gallstones who had a high probability of developing elevated serum transaminase when treated with CDC. Thus, sulfation of lithocholate may modify CDC-induced elevations of serum transaminase.

Aged↗

PubMed1981

Treatment of choledocholithiasis with oral chenodeoxycholic acid.

The aim of this study was to conduct a controlled trial of oral chenodeoxycholic acid in the management of radiolucent choledocholithiasis. Thirteen patients were randomized in double-blind fashion to receive either 750 mg/day of chenodeoxycholic acid (CDCA) or a placebo. After 4 months, those who had the placebo were administered CDCA; those who had received CDCA and showed a 25% or more decrease in the size of stones (evaluated blindly) received CDCA for an additional 4 months. Five of the 13 patients did not complete the study; four (one initially placebo and three CDCA) because acute biliary symptoms mandated operative intervention and one (initially placebo, then CDCA) because of asymptomatic elevations of the serum transaminase levels. Patients who were withdrawn from the study had significantly larger stones (P less than 0.02) (mean largest diameter, 11.4 mm +/- 1.6 SEM) than those who completed the study (6.5 +/- 0.5). Of the eight patients who completed the study, two of the three who received CDCA initially for 6 to 8 months experienced complete disappearance of stones; all five patients who took the placebo failed to show dissolution, and one of these subsequently had dissolution of stones after 8 months of CDCA. Biliary lipid analyses during treatment showed bile unsaturated with respect to cholesterol in the three patients whose stones dissolved with CDCA therapy. In conclusion, a patient with partial dissolution of stones and unsaturated bile after 4 months of CDCA probably will have complete dissolution of stones after 6 to 8 months of CDCA.

Administration, Oral↗

PubMed1979

Gallstone dissolution--a progress report.

Cholesterol gallstone formation occurs in three stages. First, the bile must be saturated with cholesterol, thereby allowing cholesterol crystals to form. Then, nucleation and growth of the gallstone can occur, although little is known about these latter two stages. Therapy for dissolution of gallstones is directed at desaturating the bile. Chenodeoxycholic acid (CDCA), the most extensively tested agent, is successful in dissolving 60 per cent of radiolucent gallstones; however, long-term safety remains to be demonstrated. Ursodeoxycholic acid (UDCA), the 7 beta epimer of CDCA, is a promising agent for cholesterol gallstone dissolution, but it, other potential agents, and dietary manipulations require more extensive study. An important problem, the prevention of recurrence of gallstones after dissolution, also needs resolution. Medical dissolution probably will be applicable as an alternative to cholecystectomy for most patients with radiolucent gallstones, but the specific relative indications remain to be determined. A variety of modalities, both medical and surgical, are being used for the treatment of retained or reformed bile duct stones. These include T-tube infusions, oral CDCA, and extraction either through the T-tube tract or after endoscopic papillotomy. Further studies, including controlled trials, are necessary to determine the relative indications for these methods.

Animals↗

PubMed1979

Cholesterol gallstone formation and prevention by chenodeoxycholic and ursodeoxycholic acids. A new hamster model.

Prior animal models of cholesterol gallstone formation have been criticized for their dissimilarity to the conditions of humans with gallstones. We present a new hamster model of cholesterol cholelithiasis that more closely approximates the human situation. Sixty female Golden Syrian hamsters (average weight 83.2 +/- 3.4 g) were allocated to six groups of 10 animals each. Groups were fed standard diet (containing 0.8 gm cholesterol/g of food) or increased cholesterol diet (containing 2.4 mg cholesterol/g of food), with or without ethinyl estradiol, 15 micrograms/kg/d. Two groups receiving both increased cholesterol and ethinyl estradiol also received either chenodeoxycholic acid or ursodeoxycholic acid, 20 mg/kg/d. The animsl were sacrificed at 12 wk. Cholesterol gallstones (78.3 +/- 5.0% cholesterol by weight) formed in 30% of the animals fed ethinyl estradiol, 50% of those fed increased cholesterol, and 90% of those fed the combination of both. Bile was saturated in all three groups, with the saturation index of the combination group (2.08 +/- 0.17) being the highest. In both groups receiving bile acid therapy, no gallstones were found, and the bile remained unsaturated. For the bile acid-fed groups, both hepatic HMG-CoAR and hepatic cholesterol 7 alpha-hydroxylase activities were reduced (P less than 0.01) when compared to the group fed standard diet and to the grou fed the combination. Thus, a new animal model of cholesterol gallstone formation has been developed in which chenodeoxycholic acid and ursodeoxycholic acid therapy prevented gallstone formation through mechanisms similar to those reported in cholesterol gallstone patients.

Animals↗

PubMed1978

Gallstones. The present and future of medical dissolution.

Adequate concentrations of bile acids and phospholipids are necessary to keep cholesterol in solution in bile. When the amount of cholesterol exceeds the capacity of bile acids and phospholipids to keep the cholesterol in micellar solution, bile becomes supersaturated; then, under appropriate conditions, cholesterol crystals form and gallstones may develop. Current dissolution therapy is aimed at desaturating the bile, thereby shifting the equilibrium of cholesterol from a crystalline phase back toward a micellar state, thus permitting gallstones to dissolve. Chenodeoxycholic acid is the drug being most extensively tested for efficacy in dissolution; at present, it is successful in about 60 per cent of cases. The primary mechanism of action appears to be suppression of biliary secretion of cholesterol. Further experience is needed to confirm the safety of chenodeoxycholic acid, to gain more precision in patient selection, and to determine ideal dose. The role of chenodeoxycholic acid in prophylaxis and in prevention of recurrence needs further study. Other potential agents for dissolution also deserve investigation.

Adult↗