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H Y Mok

Publications and source records attributed to H Y Mok.

31 records · Page 2Linked to original sources

Determination of cholesterol absorption in man by intestinal perfusion.

In this study a technique is described for estimating net absorption of total cholesterol (endogenous + exogenous) that enters the intestine. The method employs intubation of patients with a 3-lumen tube that contains a 10-cm mixing segment in the duodenum and a 100-cm absorption segment in the jejunum. A liquid formula diet containing varying amounts of exogenous cholesterol is infused continuously into the upper duodenum for a period of several hours; the formula diet stimulates constant contraction of the gallbladder and thus provides for continous secretion of biliary cholesterol sitosterol as a marker, the input of endogenous + exogenous cholesterol can be measured at the end of the 10-cm mixing segment. Net cholesterol absorption is estimated from the disappearance of cholesterol relative to beta-sitosterol over the next 100-cm of jejunum. When radioactive cholesterol was also used as a marker, radioactivity usually disappeared more rapidly than the mass of choleesterol over the absorption segment; this suggests that a significant amount of isotope exchange occurs in the upper intestine. Using beta-sitosterol as a marker, the extent of exchange can be determined. In six patients, cholesterol inputs ranged from 51 to 118 mg/hr, and net percentage absorption was 34-56%. When inputs of cholesterol were acutely increased by enhancing exogenous cholesterol, absolute absorption was uniformly increased, but percentage absorption either remained the same or was decreased somewhat. Changine inputs of beta-sitosterol had a striking effect on cholesterol absorption, and relatively small increments of beta-sitosterol almost always produced corresponding reductions in uptake of cholesterol. The intestinal perfusion method appears to provide certain advantages over previous techniques for estimating total cholesterol entering the upper intestine, including that derived from both endogenous and exogenous sources. Measurements can be made over short periods of time, and the method allows for determination of effects of acute changes in the intestinal milieu on cholesterol absorption. Finally, the technique defines the extent of isotope exchange between cholesterol in the intestinal mucosa and in the lumen.

Adult↗

Chylomicron clearance in normal and hyperlipidemic man.

A method has been developed for measurement of fractional clearance rates of chylomicrons in man. The technique employs constant infusion of emulsified fat into the duodenum at a rate of 200 mg/kh/hr. After 5 hr of infusion, concentrations of triglycerides (TG) in the chylomicron fraction become constant for the subsequent 5 hr. Since the input of chylomicron-TG is known, fractional removal rates can be calculated from steady-state plasma levels. In 21 patients with normal TG levels, clearance rates for chylomicrons were extremely rapid (t1/2 for chylomicron-TG equals 4.5 +/- 2.9 (SD) min). In 30 patients with endogenous hypertriglyceridemia, clearance was generally prolonged (t1/2 equals 23 +/- 5.5 min). This delay in chylomicron clearance could have been due either to a defect in removal of all TG-rich lipoproteinarticles; a generalized defect in clearance capacity for plasma TG was apparently ruled out for most patients by the further observation that reduction of endogenous TG by caloric restriction caused chylomicron removal to return to normal. These studies also showed that endogenous-TG is removed much less efficiently than chylomicron-TG, and in some patients, this discrepancy is particularly marked.

Adult↗

Chenodeoxycholic acid treatment of gallstones. A follow-up report and analysis of factors influencing response to therapy.

We treated 70 patients with gallstones with chenodeoxycholic acid over 3 1/2 years and analyzed the factors influencing the outcome of therapy. This treatment was unsuccessful in 11 patients with radiopaque gallstones and in seven with nonfunctioning gallbladders, but 64 per cent with radiolucent gallstones treated for six months or more showed partial or complete gallstone dissolution, and of those whose bile became unsaturated with cholesterol, 100 per cent had evidence of dissolution. In patients with partial or complete gallstone dissolution, the mean post-treatment biliary cholesterol saturation index--0.78 +/- 0.04 (S.E.M.)--was significantly less (P less than 0.001), and the dose of chenodeoxycholic acid (14.4 +/- 1.0 mg per kilogram of body weight per day) significantly more (P less than 0.025) than in those whose gallstones did not change (1.15 +/- 0.04 and 10.6 +/- 1.2 respectively). In patients with radiolucent gallstones, the dose of chenodeoxycholic acid should be based on body weight; 14 to 15 mg per kilogram of body weight per day effectively lowers the saturation index and dissolves gallstones.

Adult↗

Liver structure and function in cholelithiasis: effect of chenodeoxycholic acid.

Although, in suitable patients, oral chenodeoxycholic acid (CDCA) dissolves gallstones, the results of recent animal studies suggest that it might be hepatotoxic. Liver function was therefore studied in patients with gallstones before and during treatment with CDCA and liver biopsies were carried out both in patients with cholelithiasis given bile acid therapy and in those who had been given no medical treatment. In 25 patients treated with 0.5-1.5 g CDCA/day (7-20 mg kg body weight(-1) day(-1)) there was no significant change in serum bilirubin, albumin, globulin, transaminase, isocitric dehydrogenase, alkaline phosphatase, and gamma glutamyl transpeptidase levels before and at monthly intervals during six months' treatment. The kinetics of bromsulphthalein (BSP) clearance and its apparent transport maximum were not significantly changed during CDCA therapy. The mean fasting serum bile acid concentrations of 18.0 +/- SEM 1.2 mumoles/litre before and 20.0 +/- 3.5 mumoles/litre during treatment were both significantly greater than control values. Liver histology was not appreciably different in 11 patients treated with CDCA from that in eight patients with untreated cholelithiasis and in three patients who had received CDCA three to four months before biopsy. These results suggest that in doses of 0.5 to 1.5 g/day CDCA is not hepatotoxic in man.

Adult↗

The control of bile acid pool size: effect of jejunal resection and phenobarbitone on bile acid metabolism in the rat.

In patients with cholesterol gallstones, there is a diminished bile acid pool and the bile becomes supersaturated with cholesterol. Medical treatment has been aimed at re-expanding the pool to improve cholesterol solubility in bile but as yet the factors controlling the size of the bile acid pool' are unknown. Therefore the role of the liver and intestine in controlling bile acid pool size in the rat was studied and the effect of experimental expansion of the pool on bile acid metabolism and bile lipid composition examined. Bile acid absorption was increased from ileum made hyperplastic by previous jejunectomy and hepatic bile acid synthesis was increased by phenobarbitone treatment. Both jejunal resection and phenobarbitone significantly increased the size of the bile acid pool from 32.2 +/- SEM 0.94 mumoles/100 g body weight to 42.2 +/- 1.71 and 44.4 +/- 2.03 respectively. However, the effects of these experimental manipulations on bile acid secretion rate, enterohepatic cycling frequency, and synthesis rates were quite different. Jejunectomy caused a 56% increase in bile acid secretion and more rapid cycling of the bile acid pool but the enhanced absorption did not depress bile acid synthesis. In contrast, phenobarbitone markedly increased synthesis from 14.5 +/- 1.42 mumoles.100 g BW(-1). 24 hr(-1) to 25.9 +/- 3.19 but there was no significant change in bile acid secretion and the choleresis seen after phenobarbitone was mainly due to an increase in the bile acid-independent fraction of bile flow. In these experimental studies in the rat, expansion of the bile acid pool did not significantly change bile lipid composition or cholesterol solubility in bile.

Animals↗