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Biomedical subjects

R H Dowling

Publications and source records attributed to R H Dowling.

At least 127 records · Page 7Linked to original sources
PubMed1974

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↗
PubMed1974

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↗
PubMed1973

Serum lipids in cholelithiasis: effect of chenodeoxycholic acid therapy.

Hypercholesterolaemia has been predicted as a possible complication of chenodeoxycholic acid treatment for gall stones. To exclude this, fasting serum lipids were measured in patients with stones before and at monthly intervals for six months after starting chenodeoxycholic acid. Before treatment half of a group of 36 patients with presumed cholesterol gall stones had serum cholesterol levels exceeding 260 mg/100 ml or serum triglyceride values greater than 160 mg/100 ml or both; these lipid levels were significantly greater than those in control subjects matched for age and sex. Treatment with chenodeoxycholic acid (0.5-1.5 g/day by mouth) did not change serum cholesterol levels but did significantly reduce serum triglyceride concentrations from a pretreatment level of 118 (+/- S.E. of mean 11.7) mg/100 ml to 95 (+/- 7.2) mg/100 ml after six months of therapy. The mechanism of this triglyceride-lowering action of chenodeoxycholic acid is not known, but it may have therapeutic value in patients with hypertriglyceridaemia.

Adult↗
PubMed1973

Liver structure and function following small bowel resection.

The observation that patients with extensive small bowel resection have impaired hepatocellular function with reduced BSP clearance and fatty change in biopsies from the liver led to a systematic study of liver structure and function following proximal and distal small bowel resection in the rat. While anaesthesia and surgery impaired BSP clearance per se, small bowel resection further reduced BSP clearance with impairment of both uptake and excretion phases of BSP excretion. The increased BSP retention was more marked after distal than after proximal small bowel resection, but in both experimental groups the abnormalities of BSP excretion spontaneously returned to normal three to four weeks after surgery. Circulating liver enzymes were normal but serum alkaline phosphatase was significantly depressed, particularly after distal resection. Isoenzyme studies showed that the depression of serum AP was due to a reduced intestinal isoenzyme. While serum levels remained consistently depressed up to eight weeks after proximal resection, in parallel with mucosal regeneration, serum AP returned to normal two to four weeks after ileectomy. While these minor changes in hepatic structure and function would normally be of little clinical importance, the additional insult of hepatic dysfunction may well be important in malnourished patients after extensive small bowel resection.

Adult↗