Biomedical subjects

M G Korman

Publications and source records attributed to M G Korman.

At least 91 records · Page 5Linked to original sources

PubMed1975

Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared.

Among 120 consecutive patients with chronic active liver disease (CALD) randomized to different treatments, those receiving maintenance doses of prednisone 20 mg daily (Pred), prednisone in doses given on alternate days and titrated to secure resolution of clinical and biochemical abnormalities (Pred-Titrad), or a combination of prednisone 10 mg and azathioprine 50 mg daily (Comb) survived and underwent resolution of clinical and biochemical features of disease more often than a control group receiving placebo or azathioprine 100 mg daily. Histological remission occurred significantly more often with Pred and Comb than with other regimens. Major side-effects of therapy were commoner with Pred than with Comb or Pred-Titrad, which did not differ. We conclude that Comb is the initial treatment of choice for CALD, since clinical, biochemical, and histological resolution of disease activity occurs as often as with Pred, whereas early side-effects are significantly less frequent.

Adolescent↗

PubMed1975

Metabolism of lithocholate in healthy man. II. Enterohepatic circulation.

Studies were carried out in healthy subjects to characterize the enterohepatic circulation of lithocholate and its metabolites. When mixed with bile and infused into the jejunum, radiolabeled lithocholylglycine was absorbed more rapidly and more efficiently than sulfolithocholylglycine, based on recovery from bile. When these metabolites were administered at 1800 hr in a liquid test meal containing radiolabeled taurocholate as an absorbable marker, 60% of lithocholylglycine was conserved, based on recovery of radioactivity in fasting bile the following morning, but only 20% of sulfolithocholylglycine was conserved. Iotope dilution studies in 4 subjects showed that daily input of lithocholate into the bile acid pool averaged 100 mg per day, about one-third to one-half of the chenodeoxycholic acid synthesis, but the t 1/2 was extremely short (0.74 day). The small lithocholate pool (about 100 mg) could be explained by rapid fecal excretion caused by sulfation which decreases passive absorption in the jejunum and active absorption in the ileum. Experiments with [35S]sulfo- [3H]lithocholylglycine indicated little desulfation during enterohepatic cycling but rapid desulfation in the distal intestine, with absorption of 35S (presumably as sulfate) followed by urinary excretion. A decreasing 35S:3H ratio in bile indicated that some steroid moiety was conserved to be resulfated. These studies indicate that considerable lithocholate is absorbed from the distal intestine in healthy subjects but efficient sulfation results in rapid fecal excretion, so that the total lithocholate pool remains small. A multicompartment model, previously used to describe the metabolism of the steroid and amino acid moieties of the major conjugated biliary bile acids, was extended to encompass lithocholyl conjugates and their sulfates.

Chenodeoxycholic Acid↗

PubMed1975

Biliary bile acid composition in Wilson's disease.

Biliary bile acid composition and pattern of bile acid conjugation with glycine or taurine were found to be within normal limits in six patients with documented Wilson's disease. Four patients had previous biopsy evidence of cirrhosis (three with active hepatitis), but most conventional liver function tests gave normal results at the time of the study. Serum levels of conjugates of cholic acid, measured by radioimmunoassay, were not increased. However, plasma disappearance if intravenously injected glycine conjugate of cholic acid was significantly delayed in all subjects, suggesting that this is a more sensitive test of hepatic excretory function and may be of value for assessing hepatic function in patients with this rare genetic disorder. No evidence of a primary disturbance in bile acid metabolism was found in these patients.

Adolescent↗

PubMed1975

Plasma disappearance of radioactivity after intravenous injection of labeled bile acids in man.

The kinetics of disappearance of radioactivity from plasma after intravenous injection of radiolabeled bile acids was characterized in healthy subjects. Cholic and chenodeoxycholic acids and their N-glycine and N-taurine conjugates were studied along with the secondary bile acid, deoxycholic acid, and a synthetic conjugated bile acid, dehydrocholyltaurine. Disappearance of each primary bile acid was rapid and could be described by a biexponential curve (t 1/2 the first component, 1.7 to 3 min; second component, 7 to 16 min). Cholyglycine and cholyltaurine had identical disappearance rates which were significantly faster than the disappearance rates of chenodeoxycholylglycine and chenodeoxycholyltaurine, which were also identical. Radioactivity of a conjugated bile acid disappeared more rapidly than that of its unconjugated form, but all of these differences, although consistent, were small. Deoxycholic acid radioactivity disappeared slightly more slowly than that of the primary bile acids. In vitro, dihydroxy bile acids were bound by serum proteins more completely (96 to 98%) than trihydroxy bile acids (83 to 91%), whether free or conjugated, and binding was unrelated to bile acid concentration. Thus, plasma disappearance rates were related to the degree of protein binding to some degree in that those bile acids which were more tightly bound had the longer t 1/2 values. However, dehydrocholyltaurine showed little protein binding (42%), yet had the slowest disappearance rates; t 1/2 values averaged 4 and 36 min for the two components of the disappearance curve. The results suggest that the residence time of any bile acid in blood is extremely short, and that measurable concentrations of serum bile acids persist only because of continuous intestinal absorption. It is speculated that the reported difference between the pattern of fasting state serum bile acids and biliary bile acids is explained by differences in intestinal absorption and hepatic uptake of individual bile acids.

Adult↗

PubMed1975

Metabolism of lethocholate in healthy man. I. Biotransformation and biliary excretion of intravenously administered lithocholate, lithocholylglycine, and their sulfates.

The metabolism of intravenously injected radiolabeled lithocholate, lithocholylglycine, and their 3alpha-sulfate esters was characterized in healthy subjects. Lithocholate radioactivity was excreted rapidly and predominantly in bile; the excreted radioactivity had the chromatographic properties of glycine and taurine conjugates of lithocholate, of which 60% were sulfated. Lithocholylglycine also was excreted rapidly and predominantly in bile, and 60% of excreted radioacitvity was sulfated. Sulfolithocholate radioactivity was only partially conjugated (about 60%) in association with biliary excretion. Sulfolithocholylglycine was excreted unchanged in bile. Neither sulfated derivative showed appreciable excretion in urine, although both were excreted more slowly in bile than unsulfated free or conjugated lithocholate. The data suggest that unconjugated lithocholate which is absorbed is completely conjugated and partially sulfated before excretion which occurs exclusively in bile. Since sulfation is not complete, some unsulfated lithocholate is always present in bile. This conjugated but unsulfated lithocholate, if reabsorbed, would be again partially sulfated during its next enterohepatic circulation. Thus, the end result of these biotransformations would be for absorbed lithocholate to be excreted in bile mostly, but not entirely as the sulfated conjugates.

Bile↗

PubMed1975

Metabolism of lithocholate in healthy man. III. Plasma disappearance of radioactivity after intravenous injection of labeled lithocholate and its derivatives.

The plasma disappearance of intravenously injected radiolabeled lithocholate, lithocholylglycine, and their respective 3alpha-sulfates was defined in healthy subjects. Binding of these bile acids to serum protein in vitro was measured by ultrafiltration. Lithocholate and lithocholylglycine rapidly disappeared from plasma (t1/2 less than 3 min), showing a behavior similar to that of the other major primary bile acids present in man. However, after 15 min, when 99% of the radioactivity had been cleared, the disappearance curve flattened, and chromatography suggested that the chemical form of circulating radioactivity had become sulfolithocholylglycine, the end product of hepatic metabolism of lithocholate in man. Injected sulfolithocholate and sulfolithocholylglycine were cleared about one-fourth as rapidly. Lithocholate and its derivatives were tightly bound to serum proteins (87 to 99%); for a given steroid moiety and mode of conjugation, binding was altered slightly by sulfation, but all sulfated derivatives were tightly bound (greater than 95%) to serum protein. The results indicate that lithocholate, which enters the plasma compartment, whether unconjugated, conjugated, or conjugated and sulfated, will be protein-bound but nonetheless will be rapidly cleared from plasma.

Adult↗

PubMed1975

Fasting serum bile acid levels in the primary hyperlipoproteinemias.

A newly developed radioimmunoassay specific for conjugates of cholic acid (CCA) was used to measure the fasting serum levels of these bile acids in 233 patients with primary hyperlipoproteinemia classified as type IIa, IIb, III, IV, or V hyperlipoproteinemia as well as in 80 healthy control subjects. Subjects with type IIa hyperlipoproteinemia had significantly lower levels of CCA (0.9 plus or minus 0.06 muM, mean plus or minus SE) than did healthy controls (0.50 plus or minus 0.08 muM). Patients with type IIb, III, IV, and V hyperlipoproteinemia had values similar to those of the control group. The abnormally low fasting value of CCA in type IIa patients is considered to reflect decreased secretion of bile acid into the intestine in such patients, who are known to have defective bile acid synthesis rates and decreased bile acid pool sizes.

Adult↗

PubMed1974