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Biomedical subjects

R D Soloway

Publications and source records attributed to R D Soloway.

At least 91 records · Page 5Linked to original sources

Effects of meals and interruption of enterohepatic circulation on flow, lipid composition, and cholesterol saturation of bile in man after cholecystectomy.

In 4 patients studied after cholecystectomy and common-duct exploration for cholesterol gallstones, bile salt (BS) and phospholipid (PL) output and bile flow increased significantly in response to breakfast, but cholesterol (Ch) output was unaltered. Simultaneously, Ch concentration decreased while PL and BS concentrations did not change. The degree of Ch saturation of bile, [BS PLUS PL]/[ch], decreased in each study, whether or not the original ratio indicated Ch supersaturation; in 3 of 5 studies, an initially super-saturated bile became unsaturated with Ch in response to breakfast. No significant changes were noted after lunch. During interruption of enterohepatic circulation (EHC), studies with radiolabeled bile acids indicated that the increased bile acid output in response to meals was secondary to increased recirculation of intestinal bile acids rather than to de novo bile acid synthesis. This mechanism may account for the adequate delivery of BS and for the decreased degree of Ch saturation of bile postprandially in cholecystectomized patients.

Aged↗

Evaluation of radiographic lucency or opaqueness of gallstones as a means of identifying cholesterol or pigment stones. Correlation of lucency or opaqueness with calcium and mineral.

A major criterion for the selection of patients with gallstones for treatment with chenodeoxycholic acid is the radiographic demonstration of lucent gallstones. In this study, we sought to evaluate the degree of selectivity of that criterion for distinguishing patients with cholesterol stones from those with pigment stones and to define the determinants of stone lucency or opaqueness. Of 92 lucent stones, 14% were pigment stones; and of 18 of opaque stones, 33% were cholesterol. Thus, the criterion of stone lucency allows inclusion of a significant number of subjects (14%) with lucent pigment stones, which may account for about one-half of the reported 33% incidence of treatment failures with chenodeoxycholic acid. Conversely, of patients with opaque stones, the one-third with cholesterol stones would be excluded from chenodeoxycholic acid treatment. Calcium is the major metal of both types of stones. However, opaque stones contain 6 times more calcium than lucent stones, which accounts for the difference in radiographic appearance.

Bile Pigments↗

Triketocholanoic (dehydrocholic) acid. Hepatic metabolism and effect on bile flow and biliary lipid secretion in man.

[24-(14)C]Dehydrocholic acid (triketo-5-beta-cholanoic acid) was synthesized from [24-(14)C]cholic acid, mixed with 200 mg of carrier, and administered intravenously to two patients with indwelling T tubes designed to permit bile sampling without interruption of the enterohepatic circulation. More than 80% of infused radioactivity was excreted rapidly in bile as glycine- and taurine-conjugated bile acids. Radioactive products were identified, after deconjugation, as partially or completely reduced derivatives of dehydrocholic acid. By mass spectrometry, as well as chromatography, the major metabolite (about 70%) was a dihydroxy monoketo bile acid (3alpha,7alpha-dihydroxy-12-keto-5beta-cholanoic acid); a second metabolite (about 20%) was a monohydroxy diketo acid (3alpha-hydroxy-7,12-di-keto-5beta-cholanoic acid); and about 10% of radioactivity was present as cholic acid. Reduction appeared to have been sequential (3 position, then 7 position, and then 12 position) and stereospecific (only alpha epimers were recovered). Bile flow, expressed as the ratio of bile flow to bile acid excretion, was increased after dehydrocholic acid administration. It was speculated that the hydroxy keto metabolites are hydrocholeretics. The proportion of cholesterol to lecithin and bile acids did not change significantly after dehydrocholic acid administration. In vitro studies showed that the hydroxy keto metabolites dispersed lecithin poorly compared to cholate; however, mixtures of cholate and either metabolite had dispersant properties similar to those of cholate alone, provided the ratio of metabolite to cholate remained below a value characteristic for each metabolite. These experiments disclose a new metabolic pathway in man, provide further insight into the hydrocholeresis induced by keto bile acids, and indicate the striking change in pharmacologic and physical properties caused by replacement of hydroxyl by a keto substituent in the bile acid molecule.

Bile↗

Water content of gallstones: location and contribution to a hypothesis concerning stone structure.

The water content of black pigment and cholesterol gallstones was evaluated with the use of moisture evolution analysis, electron spectroscopy for surface analysis, and X-ray diffraction. X-ray diffraction identified complex hydrated hydroxyapatite compounds in two stones. Moisture evolution analysis demonstrated that 18 pigment gallstones contained between 0.83 and 6.87% water; six cholesterol stones contained 0 to 0.27% (p less than 0.001). When black stones were subdivided into subgroups containing large proportions of pigment, phosphate, or carbonate, the proportion of water evolved at each temperature was the same. Water content was inversely related to carbonate content (r = -0.81) and did not correlate well with other stone components. Electron spectroscopy for surface analysis independently suggested that water of hydration was present since the ratio of oxygen to other elements exceeded ratios in any known compound in stone. A peripheral-central gradient for water was absent in one stone which was analyzed in peripheral mid-, and central portions. Progressive removal of the surface of previously ground stone particles using an argon beam followed by repeated electron spectroscopy for surface analysis indicated that much of the water was present in the outer 20 to 50 A of the particles. The data are consistent with the hypothesis that pigment stones form by deposition of calcium salts on an organic matrix and that hydrated water is associated with thin layers of calcium salts. These layers may be distributed throughout the stone; powdering appears to fractionate stones through these areas of hydrated calcium salts since oxygen was in highest concentration on the surface of powder particles.

Bilirubin↗

Pigment gallstone disease: Summary of the National Institutes of Health--international workshop.

This report summarizes the proceedings of the first National Institutes of Health--International Workshop on Pigment Gallstone Disease. The meeting held at the University of Pennsylvania in May, 1981 consisted of eight sessions in which the following aspects of pigment gallstone disease were discussed: (a) classification; (b) epidemiology; (c) radiographic assessment; (d) gallstone composition; (e) composition of bile; (f) pathogenesis; (g) animal models, genetics, and computer analysis, and (h) medical treatment. The interaction of participants interested in various aspects of pigment stone disease was stimulating. This workshop should be a major stimulus for future studies in this relatively neglected, but important area of biliary tract lithiasis.

Animals↗