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Biomedical subjects

S M Strasberg

Publications and source records attributed to S M Strasberg.

At least 127 records · Page 7Linked to original sources

Results of combined biliary drainage and cholecystokinin cholecystography in 81 patients with normal oral cholecystograms.

Combined biliary drainage-cholecystokinin cholecystography (BD-CC) was evaluated in 81 patients with pain indistinguishable from biliary colic, but normal conventional diagnostic tests. The test was performed using a new technique of intubation and aspiration, with a steerable catheter and sump duodenal tube. Both positive and negative groups were followed. One third of patients had positive tests, and almost all had pathologic gallbladders, and a symptomatic outcome equal to that obtained by cholecystectomy for cholelithiasis diagnosed by conventional means. Some patients with severe pain had cholecystectomy despite a negative report. Pathologic findings were significantly fewer, and symptomatic outcome less satisfactory but sufficiently good to suggest that painful functional gallbladder abnormalities, not amenable to diagnosis by BD-CC exist. Hypercontraction was found to be a reliable index of gallbladder pathology. A false bilirubin precipitate was identified in some patients; this precipitate may be recognized by microscopy and pH testing. This finding should reduce false-positives in BD-CC.

Adult↗

[14C]erythritol clearance and canalicular bile acid-independent flow in the baboon.

The use of [14C]erythritol for the quantitative assessment of hepatic bile formation has been studied in baboons using sodium taurocholate to generate canalicular bile flow. It has been found that increments in [14C]erythritol clearance are equal to taurocholate-induced increments in bile flow, but there was no change in [14C]erythritol clearance when bile flow was increased by secretin. No evidence was found to support the view that bile acids affect bile acid-independent bile flow.

Animals↗

The Sugiura procedure for bleeding esophageal varices: a modification.

The Sugiura procedure is an operation for control of bleeding esophageal varices. Splenectomy, extensive paraesophagogastric devascularization, and transection and anastomosis of the esophagus are performed through two incisions. The modifications described by the authors, such as the single thoracoabdominal incision and use of a stapler, simplify and shorten the operation. Preliminary results in nine patients are encouraging.

Esophageal and Gastric Varices↗

The effect of elevated biliary tract pressure on biliary lipid metabolism and bile flow in nonhuman primates.

The effects of low (control), moderate, and high biliary tract pressures on biliary lipid metabolism and bile flow were studied in six rhesus monkeys and two baboons. Moderate pressures did not influence bile flow or biliary lipid metabolism. High biliary tract pressures produced significant reductions in bile flow and the secretion rates of bile salts, phospholipids, and cholesterol, but cholesterol saturation in bile improved. High pressure also completely inhibited bile salt synthesis, and the bile salt pool size decreased slightly due to continuing small losses in urine and bile samples. During the high pressure period bile salts accumulated in the liver and peripheral tissues. After pressure had been returned to control levels, bile flow and biliary lipid secretion rates returned to normal levels. Bile salt secretion recovered more slowly than secretion of the other lipids and bile became more saturated with cholesterol than in the control period. Bile salt synthesis resumed approximately 10 hr after pressure had been returned to control levels. The high biliary tract pressures induced in these studies are no known to occur in about 25% of normal human subjects. (J Lab Clin Med 99:342, 1982.)

Animals↗

Effect of ethanol on formation of bile.

The effects of ethanol on bile formation have been studied in the rat, dog, and man, in both acute and chronic models. The acute and chronic effects differ. Given acutely, ethanol suppresses bile flow and bile acid secretion rate. Chronic administration appears to increase both components of canalicular flow and bile acid secretion rate. Intestinal and hepatic actions are probably involved in the latter effect. Secretion of other biliary lipids and diagnostic anions are also reduced by ethanol.

Animals↗

Prevention of cholesterol gallstones by lignin and lactulose in the hamster.

The effect on prevention of cholesterol gallstones by a nonfermentable type of fiber, lignin, and a fermentable fiber analogue, lactulose, was studied in hamsters fed an essential fatty acid deficient diet. Control animals had a high incidence of cholesterol gallstones (21 of 24) and lithogenic bile (lithogenic index 1.08). Animals fed lignin had significantly fewer gallstones (11 of 25), improved cholesterol saturation of gallbladder bile, and increased fecal bile acid excretion. Lactulose-fed animals had significantly fewer gallstones (12 of 24) but no significant change in cholesterol saturation of gallbladder bile or in fecal bile acid excretion. Serum cholesterol concentration was reduced, however, and fecal neutral steroid excretion was increased. Gallstones were completely prevented in animals fed both lignin and lactulose (0 of 22), but gallbladder bile cholesterol saturation was not significantly different from the lignin-fed group. Gallbladder bile mucopolysaccharide concentrations did not differ among groups. Lignin appears to prevent cholesterol gallstones in this model by improving cholesterol saturation of bile. The mechanism of action of lactulose is not yet clear.

Animals↗

Ileal excretion and bacterial modification of bile acids and cholesterol in patients with continent ileostomy.

Bile acid (acidic sterol) and neutral steroid excretion were determined in 15 patients, five with conventional ileostomy, five with continent ileostomy, and five with continent ileostomy and an ileal resection. Acidic sterol losses were normal in conventional ileostomy patients and not significantly increased in those with continent ileostomy alone. Bile acid excretion rates were significantly increased in patients with a continent ileostomy and an ileal resection. Neutral steroid excretion was similar in all groups and not different from normal. Deoxycholic acid was not detected in ileal effluent of patients with conventional ileostomy and less than 2% of neutral steroid excreted was in the form of bacterial metabolites of cholesterol. The same was true of six of the 10 patients with continent ileostomies; in the other four patients at least 10% of acidic or neutral steroids were excreted as secondary bile acids or as a coprostanol. Modification of steroids was not related to ileal resection. Continent ileostomy was associated with a significant increase in percentage water content and a reduction in the pH of ileal effluent.

Adult↗

Unilateral hepatic duct obstruction in the primate.

The effects of obstruction of one hepatic duct were investigated in two studies in the rhesus monkey. A model to divide bile flow from the two sides of the liver was developed in the first study. Bile flow from one side of the liver was obstructed and backflow from the obstructed biliary tract was investigated in five animals. Test solutions containing sulfobromophthalein (BSP) and conjugated cholic acid-14C were introduced into the obstructed side of the liver at pressures below and above the maximum secretory pressure. These solutes were detected in the circulation and in the bile on the free side of the liver. BSP, secreted on the free side, was conjugated normally (52.7 percent) for this species. There was also backflow of water from the obstructed side and continuing secretion into the obstructed side. It was determined that there were no functionally significant biliary communications between the two separately cannulated portions of the liver. In the second study, graded unilateral obstruction and recovery were studied in five animals. Bile flow, eyythritol-14C clearance, and bile acid, bilirubin, and bicarbonate secretion rates were reduced during obstruction and recovery. The bile:plasma ratio of erythritol-14C fell significantly (1.13 to 0.97) and the bicarbonate concentration increased during partial obstruction. On the free side, bile flow, erythritol-14C clearance, and bile acid secretion rates increased during obstruction. The increase in bile flow was due largely to an increase in canalicular bile acid-dependent flow. The studies indicated that reduced bile flow during acute obstruction is due to both hydrostatic backflow and secretory failure. The latter occurs mainly at the canalicular level, whereas the bile ductules are spared at least relatively. During acute obstructions compensations in unobstructed portions of the liver are due to increased secretion of solute at the canaliculus.

Animals↗

The contribution of the extrahepatic bile ducts to bile formation.

This study was performed to determine the contribution of the extrahepatic bile ducts to bile flow in the rhesus monkey. Bile flow from the two sides of the liver was divided. The major extrahepatic bile ducts remained connected to one side of the liver only. Bile flow, and the concentrations of [14C]erythritol, bicarbonate, bile acid, and bilirubin in bile samples from the two sides of the liver, in the fed state were measured and compared. An estimate of the net flow from the extrahepatic ducts was obtained from the [14C]-erythritol concentrations on the two sides of the liver and the bile flow rate on the side with the extrahepatic ducts. The [14C]erythritol bile-plasma ratio was significantly lower in bile collected from the side with the extrahepatic bile ducts, than in bile from the other side of the liver. About 10% of total hepatic bile flow originated in the extrahepatic bile ducts, in the fed state. The bicarbonate-[14C]erythritol concentration ratio was significantly higher in bile from the side with the extrahepatic bile ducts. Bicarbonate - bile acid, and bicarbonate-bilirubin concentration ratios were also significantly higher in bile from the side of the liver with the extrahepatic ducts. The extrahepatic bile ducts have a physiologically significant role in the secretion of bile water. Bicarbonate is secreted in association with water in the extrahepatic ducts.

Animals↗

Effect of bile acid synthesis rate on cholesterol secretion rate in the steady state.

In order to discover the effect of bile acid synthesis on cholesterol secretion into the bile, 7 rhesus monkeys were studied at various stable interruptions of the enterohepatic circulation of bile acids. In 4 animals, 2.5 and 7.5% interruptions were compared; 2.5 and 15% interruptions were compared in 5 animals. There was a significant decrease in the cholesterol secretion rate, 0.048 mmoles per 24 hr +/- 0.016 (SD), and a significant increase in bile acid synthesis rate, 0.62 mmoles per 24 hr +/- 0.03 (SD) at the 7.5% interruption. No significant changes in bile acid or phospholipid secretion rates occurred. Therefore, bile acid synthesis rate influences the cholesterol secretion rate in the chronic stable state. At 15% interruption there was a significant decrease in the bile acid secretion rate from 13.4 mmoles per 24 hr +/- 1.8 (SD) to 8.0 mmoles per 24 hr +/- 2.4 (SD), suggesting that the maximum percentage interruption of the enterohepatic circulation of bile acids, at which the bile acid synthesis rate is maintained in this species, has been overestimated. A large variation in cholesterol secretion rate was found in the 7 animals when the 2.5% interruption was examined alone. Bile acid secretion and synthesis rates were considerably more stable at this interruption. Additional determinants of cholesterol secretion into the bile which are independent of bile acid metabolism probably exist.

Animals↗

Pathogenesis of human cholesterol cholelithiasis.

The pathogenesis of cholesterol cholelithiasis in humans has been studied by means of three techniques. The cholesterol-solubilizing capacity of bile may be determined by estimation of the relative composition of the three major lipid constituents of bile. Consistent reduction in the cholesterol-carrying capacity of gallbladder bile of persons with gallstones when compared with normal subjects has not been shown. Normal subjects frequently have supersaturated bile. Secretion rates of biliary lipids have been estimated by two methods; with the method that appears to be more physiologic no change in lipid secretion rates was found in gallstone patients. Bile acid pool size has been measured by isotope dilution techniques; it is reduced in patients with gallstones. It is not clear whether this reduction is important in the pathogenesis of cholesterol cholelithiasis, for the bile acid secretion rate is normal because of an increased rate of cycling of the pool through the enterohepatic circulation. The role of the gallbladder in the genesis of cholesterol cholelithiasis may be more important than has been realized.

Bile↗

The effect of bile acid synthesis on cholesterol secretion into the bile.

Cholesterol secretion into the bile has been shown to be related to the bile acid secretion rate. It has been suggested that the availability of bile acid micelles controls the entry of cholesterol into the bile. However, previous data could have been interpreted to indicate that bile acid synthesis controls cholesterol secretion into the bile. To discover whether bile acid synthesis has a significant influence on cholesterol secretion, Rhesus monkeys were studied during the period of increasing bile acid secretion and bile acid synthesis, which begins 6-10 hours following interruption of the enterohepatic circulation of bile acids. This is the only condition in which bile acid synthesis and bile acid secretion increase simultaneously. The cholesterol secretion rate fell signficantly during this period, and this effect was enhanced by phenobarbital administration. An increasing cholesterol secretion rate would have been expected if micellar attraction controlled cholesterol secretion under these conditions. Bile acid synthesis appears to have an important influence upon cholesterol secretion into the bile.

Animals↗

Analysis of the components of bile flow in the rhesus monkey.

Bile flow studies were performed in three groups of awake rhesus monkeys. In the first group, the increase in bile flow stimulated by secretin was not accompanied by an increase in erythritol-14C clearance. Resection of the gastric antrum and small intestine in the second group resulted in stable bile flow at fixed bile salt secretion rates. Linear regression lines for bile flow versus bile salt secretion rate and erythritol-14C clearance versus bile salt secretion rate were parallel, and the Y-axis intercept for the latter was consistently higher than for the former. We concluded that erythritol-14C clearance equals canalicular flow, and ductular reabsorption is constant at all bile salt secretion rates in this species. Bile flow was studied during fasting and feeding, over 6 days, in the third group. A model incorporating four bile flow components was developed and tested by multivariate regression analysis. The data fit the model quite well, explaining greater than 90% of the variation in bile flow. A method of measuring the contribution to bile flow of each of the four components is provided.

Animals↗

Bile production in fasted and fed primates.

Previous experiments have suggested differences in the bile salt independent flow rate between monkeys and dogs, and in the ability of bile salt secretion to influence bile flow. The present study was performed to determine whether the availability of food could have influenced these results. Bile flow and bile salt secretion rates were studied in fasted and fed primates. In the fasting experiments, sodium cholate, sodium taurocholate, and monkey bile were infused into the duodenum; only sodium cholate was infused in the feeding experiments. The results showed that bile flow was linearly related to the bile salt secretion rate in both fasting and feeding animals. Bile salt independent flow is extremely variable during fasting and is increased and stabilized by feeding. These studies indicate that the differences found in previous experiments are probably attributable to variations in experimental design.

Animals↗