Ursodeoxycholic acid and serum-lipids.
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Biomedical subjects
Publications and source records attributed to M C Bateson.
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In a prospective survey jejunal biopsy samples from 11 patients with multiple sclerosis on normal diets were compared with those from controls matched for age and sex. Quantitative histology, morphometry, and electron microscopy showed no difference between the two groups. Since there was no evidence that gluten sensitivity plays a role in the aetiology of multiple sclerosis, the wide adoption of gluten exclusion by patients seems unjustified.
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A case is described of severe recurrent ischaemic heart disease associated with rapidly increasing and ultimately massive hyperlipidaemia. The case is discussed, with suggestions for management of similar problems.
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96 patients with gallstones have been treated for up to four years with chenodeoxycholic acid in daily doses of 500, 750, or 1000 mg. None of the patients started on 500 mg daily showed complete gallstone dissolution. 8 out of 41 patients on 750 mg daily had complete dissolution of their radiolucent gallbladder stones after six or more months, and a further 4 showed partial dissolution. 5 out of 28 patients on 1000 mg daily had complete dissolution of their radiolucent gallbladder stones after at least six months, and a further 9 showed partial gallstone dissolution. The mean duration of therapy was greater on 750 mg than on 1000 mg/day (1.27 vs. 0.58 years), and when results were analysed after the first six months' therapy the total response-rate was significantly greater for the 1000 mg dose (12 out of 28) than for the 750 mg dose (9 out of 41). The individual response of radiolucent gallabladder stones to therapy could not be predicted from stone size, weight of patient, dosage/kg, orchange in biliary lipids. Treatment of radiolucent gallstones with chenodeoxycholic acid should start at 1000 mg daily.
Giving clofibrate 2 g daily to seven patients significantly increased the biliary cholesterol concentration while the proportion of bile acids fell. Five patients on established clofibrate treatment were given 750 mg of chenodeoxycholic acid (CDCA) daily for one month. Biliary lipid analysis after the CDCA treatment showed a significant fall in the proportion of cholesterol and a rise in that of bile acids. The serum lipid concentrations, which had already been reduced by diet and clofibrate, showed a further significant reduction after the introduction of CDCA. This study suggests that CDCA may be usefully combined with clofibrate to reverse the tendency towards cholesterol saturation of bile and enhance the effect of lowering serum lipid concentrations.
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1 Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum triglyceride level fell by 36% after dietary treatment alone (P less than 0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P less than 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P less than 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.
Individual serum bile acids were analysed by an improved gas liquid chromatography method in 12 patients with primary hyperlipidaemia. Total serum bile acid concentrations were raised in 10 subjects. Ursodeoxycholic acid was found in all 12 patients. It was present in significantly greater concentrations, accounted for a greater proportion of the total serum bile acids, and occurred more frequently than in patients with various forms of hepatobiliary disease. Patients with hyperlipidaemia had proportionately less deoxycholic acid than controls but more than patients with liver disease. There was proportionately less chenodeoxycholic acid in patients with hypercholesterolaemia, in whom the primary bile acid ratio was raised.
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To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.
Nineteen patients who received chenodeoxycholic acid 750 mg/day for six months had duodenal bile aspirated before and after treatment. In five patients with hypertriglyceridaemia but no gallstones cholesterol saturation was reversed in every case, the mean cholesterol saturation index (SI +/- standard deviation) changing from 1-38 +/- 0-31 to 0-68 +/- 0-06 (P less than 0-005). In 14 patients with gallstones there was also an improvement in bile cholesterol content, but this was not sufficient to produce mean unsaturation, saturation index changing from 1-55 +/- 0-52 to 1-13 +/- 0-43 (P less than 0-05). Only seven of 14 patients with gallstone achieved cholesterol unsaturation. In four patients with hypertriglyceridaemia and gallstones, mean unsaturation was produced and the saturation index changed from 1-70 +/- 0-45 to 0-86 +/- 0-47 (P less than 0-05). When all nine patients with hypertriglyceridaemia were grouped, the mean saturation index fell from 1-52 +/- 0-40 to 0-76 +/- 0-30 after therapy (P less than 0-001). In contrast the 10 patients without hypertriglyceridaemia showed no significant fall in saturation index which was 1-50 +/- 0-54 before and 1-24 +/- 0-40 after therapy. The ability of chenodeoxycholic acid feeding to improve bile saturation with cholesterol correlated with the presence of hypertriglyceridaemia whether or not gallstones were present. It did not correlate with gallstone dissolution or body weight.
A case of Waldenstrom's macroglobulinaemia with various clinical manifestations of the condition is presented. Hyperviscosity and respiratory complications are discussed with a brief review of the literature.
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