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Biomedical subjects

P Samuel

Publications and source records attributed to P Samuel.

At least 73 records · Page 4Linked to original sources
PubMed1981

Measurement of bile acid production in hyperlipidemic man: does phenotype or methodology make the difference?

Bile acid production has been measured in 13 studies in 10 hyperlipidemic subjects by simultaneous use of isotope dilution kinetics and chemical balance methodology. When the data of all 13 studies were averaged, the correlation between the two sets of values was negative and weak (r - 0.01, NS). However, when the correlations for normoglyceridemic and hyperglyceridemic subjects were examined separately, a strong positive correlation was found between the values obtained by the two methods in normoglyceridemic subjects (r + 0.92, P less than 0.01) but not in hyperglyceridemic subjects (r - 0.25, NS). Examination of bile acid specific activity decay characteristics in eight studies, where bile was sampled up to six times within the first 24 hr after radio-labeled bile acid infusion, revealed differences in three rate of attainment of peak specific activity and in the time taken subsequently to achieve first order kinetic decay. However, analysis of the data from these eight studies by input-output analysis yielded values for primary bile acid synthesis no different that those generated by conventional isotope dilution kinetics. Thus, bile acid production in normoglyceridemic subjects may be accurately quantitated by either isotope dilution or chemical balance methodology. Our data, as well as results from other laboratories, indicate that the values obtained are strictly comparable. On the other hand, the quantitation of bile acid production in hyperglyceridemic subjects by isotope dilution kinetics gives higher values than those obtained by chemical balance methodology, and in addition, higher values than those obtained in patients with normal plasma triglyceride levels.

Adult↗
PubMed1980

Unreliability of tritiated cholesterol: studies with [1,2-3H]-cholesterol and [24,25-3H]cholesterol in humans.

Over the past 18 months different lots of [1,2-3H]cholesterol and [24,25-3H]cholesterol were found to be radiochemically acceptable by conventional chemical and other in vitro tests, yet, when co-administered with [4-14C]cholesterol to human subjects, an abrupt fall in the 3H/14C specific activity ratio in plasma cholesterol was discovered in every case. We have concluded that all batches of [3H]cholesterol should be regarded as radiochemically unreliable unless they are shown to behave identically in all respects to [4-14C]cholesterol in an appropriate in vivo assay system.

Carbon Radioisotopes↗
PubMed1980

Cholesterol absorption in man: effect of administration of clofibrate and/or cholestyramine.

Cholesterol absorption measurements were carried out in a free-living out-patient population by a plasma isotope-ratio method previously validated for in-patients (Samuel, P., J. R. Crouse and E. H. Ahrens, Jr., 1978. J. Lipid Res. 19: 82-93). To test the reproducibility of the method in out-patients, 18 patients were tested twice: the mean intra-assay variability was +/- 6.0%. The method was then applied in 150 hyperlipidemic male out-patients, ingesting a standardized diet containing 250mg cholesterol per day, who had been randomized into four different drug-treatment groups: 1) no medication, 2) clofibrate, (2g/day), 3) cholestyramine (16g/day), or 4) both clofibrate and cholestyramine. Cholesterol absorption (as percent of the oral dose) was increased in patients receiving cholestyramine (P < 0.02) and decreased in those receiving clofibrate (P < 0.02); the group on the combined medication had the same pecent absorption as the control group. In twelve patients receiving cholestyramine, a second test of cholesterol absorption was performed 30 min after each patient had received 8g of cholestyramine. The pre-test administration of cholestyramine caused a 38% decrease in cholesterol absorption (P < 0.001), compared to results obtained when medication was withheld prior to testing. These results demonstrate that the isotope-ratio method of measuring cholesterol absorption is a reproducible procedure applicable to a free-living out-patient population, and that the hypolipidemic drugs, clofibrate and cholestyramine, significantly affect cholesterol absorption in man. The data also show that the results of measurements of cholesterol absorption can be profoundly altered by the type and timing of medication in relationship to the test meal of labeled cholesterol.

Absorption↗
PubMed1978

The relationship between serum cholesterol and fecal 7alpha-dehydroxylase activity in three ethnic groups in South Africa.

The ability of fecal bacteria to 7alpha-dehydroxylate primary bile acids was measured in vitro by incubating stool homogenates with labeled primary bile acids, and was compared to serum cholesterol levels in 4 South African groups: Rural Bantu (50 subjects), Urban White (20), Urban Bantu (17) and Urban Coloured (16). Mean serum cholesterol levels were 137 +/- 23, 213 +/- 51, 199 +/- 62 and 206 +/- 46 mg/100 ml, respectively. (Rural Bantu significantly different.) The in vitro conversion of cholic acid by stool homogenates of Rural Bantu was significantly slower than that of the Urban Whites or the Urban Bantu was significantly slower than that of the Urban Whites or the Urban Bantu in two-hour incubations. There was no difference of conversion rates in 24-hour incubations of cholic or chenodeoxycholic acids. Gas-liquid chromatographic analysis of stool homogenates showed little difference in the distribution pattern of fecal bile acids or neutral sterols. These data suggest that the activity of the intestinal bacterial flora to convert primary bile acids was significantly reduced in the Rural Bantu as compared to the other groups, corresponding with lower serum cholesterol levels. However, by the time the stools were excreted the degree of conversion was comparable in each group.

Adult↗
PubMed1978

Evaluation of an isotope ratio method for measurement of cholesterol absorption in man.

Recently an isotope ratio method (IRM) was developed for measuring cholesterol absorption in rats by analysis of radioactivity in peripheral blood (Zilversmit, D. B. 1972. Proc. Soc. Exp. Biol. Med. 140: 862-865). To validate it in man we have compared cholesterol absorption by a fecal radioactivity method (FRM) with that simultaneously measured by IRM in 14 patients (15 experiments) hospitalized on a metabolic ward. Cholesterol absorption by FRM was assayed as fecal recovery of orally administered [(14)C]cholesterol, after correction with markers for fecal flow (chromic oxide) and cholesterol degradation (beta-sitosterol). Simultaneously, [(3)H]cholesterol was administered intravenously, and the dose-normalized ratio of [(14)C]- to [(3)H]cholesterol was repeatedly assayed in plasma. After 72 hours the ratio became constant in each patient and remained so for as long as 63 weeks (five additional outpatient studies). In three patients the fecal data were unsatisfactory because of poor recoveries of chromic oxide and radioactive cholesterol. In the remaining 11 patients (12 experiments) the mean cholesterol absorption by IRM was 42.1% (range 15.7-62.9%) and by FRM 36.6% (range 13.8-58.8%). There was good to excellent agreement between the two methods in the same patient, except in one experiment. Statistical analysis of these 12 comparisons by estimating confidence intervals showed that we can be 95% confident that the two absorption methods will produce results within 5 percentage points, and 99% confident that the differences are less than 7 percentage points. Although we conclude that IRM affords results that are concordant with those obtainable by earlier validated methods, we urge that its suitability for outpatient studies be further examined in more extensive trials.

Adult↗
PubMed1978

Comparison of cholesterol turnover by sterol balance and input-output analysis, and a shortened way to estimate total exchangeable mass of cholesterol by the combination of the two methods.

Daily turnover of cholesterol obtained by the balance method was compared to daily input rates calculated by input-output analysis in 43 experiments. The mean value of input rates for kinetic data of 10.1-16.4 weeks' duration (14 experiments) was 1.05 g/day vs. the chemical turnover of 0.94 g/day (difference 10.9 percent). For decay curves of 4.8-9.9 weeks' duration (29 experiments) the mean results were 1.67 g/day vs. 1.31 g/day, respectively (difference 20.1 percent). A combination of the balance method with input-output analysis is proposed to estimate the size of M (minimum value of the total exchangeable mass of cholesterol) in short-term experiments. Using this method, the analysis of curves of 10-12 weeks' duration showed a mean difference of 7.5 percent with the analysis of curves of 50-66 weeks' duration in 17 patients. However, because of considerable variations that can occur in individual cases, it is urged that a standard correction factor not be used, either in estimating turnover data or M from 10-12 weeks' kinetic data; rather, the proposed combined method will alert the investigator to the occurrence of discrepant results.

Adult↗
PubMed1977

Measurement of daily cholesterol synthesis rates in man by assay of the fractional conversion of mevalonic acid to cholesterol.

A significant correlation has been found in man between total daily cholesterol synthesis rates as determined by sterol balance measurements and the fraction of intravenously administered R-[5-14C]mevalonic acid converted to cholesterol. In 30 studies it was found that the mean daily cholesterol synthesis rates estimated by sterol balance measurements ranged from 395 to 3047 mg/day, whereas the fractional conversion of mevalonate to cholesterol varied from 0.28 to 0.99. The two parameters correlated with a coefficient of 0.87, P less than 0.001. This method for estimating cholesterol synthesis rates requires low doses of radioisotopic materials (25 muCi of [14C]mevalonate and 5 muCi of [3H]cholesterol) and less than 1 hr of the patient's time; it can be repeated at intervals of 3 weeks and reflects cholesterol synthesis over a short period of time.

Adult↗
PubMed1977

Chylothorax: diagnosis by lipoprotein electrophoresis of serum and pleural fluid.

This report describes a 31-year-old woman who underwent a technically difficult left pneumonectomy for tuberculosis and developed thereafter a large left pleural effusion which was milky in colour. A traumatic chylothorax was suspected, and the diagnosis was confirmed by simultaneous fasting pleural and serum lipid studies and lipoprotein electrophoresis. The latter study was especially helpful in confirming the chylous nature of the fluid in that it revealed a marked chylomicron band at the origin; this was not present in the patient's serum nor in the pleural fluid of five patients with other disease states studied as controls.

Adult↗