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Biomedical subjects

K Einarsson

Publications and source records attributed to K Einarsson.

At least 145 records · Page 8Linked to original sources

Hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and biliary lipid composition in man: relation to cholesterol gallstone disease and effects of cholic acid and chenodeoxycholic acid treatment.

The present work was undertaken in order to study whether or not there is a relation between hepatic HMG CoA reductase, hepatic cholesterol concentration, and biliary lipid composition. In 55 patients (10 with adenomyoma of the gallbladder wall, 45 with cholesterol gallstones) a liver biopsy together with gallbladder and hepatic bile were obtained at laparotomy under standardized conditions. Of the gallstone patients, twelve had been treated with cholic acid and ten with chenodeoxycholic acid in a dose of 15 mg.kg-1.d-1 for 6-8 weeks prior to operation. Hepatic bile was supersaturated with cholesterol both in cholesterol gallstone patients and in patients with gallbladder adenomyoma. Treatment with cholic acid reduced the cholesterol saturation of hepatic bile, although supersaturation persisted. During chenodeoxycholic acid treatment, hepatic bile became unsaturated in most of the patients. Hepatic cholesterol concentration was about 20% higher in patients with cholesterol gallstone disease than in gallstone-free controls. During treatment with cholic acid or chenodeoxycholic acid, hepatic cholesterol concentration was normalized. Microsomal HMG CoA reductase activity was similar in males and females with cholesterol gallstone disease and not different from that seen in the gallstone-free controls. Treatment with chenodeoxycholic acid resulted in a 40% reduction of HMG CoA reductase activity. Cholic acid had no effect. In gallstone-free controls and in bile acid-treated but not in untreated gallstone patients, saturation of hepatic bile correlated with HMG CoA reductase activity. It is concluded that treatment with chenodeoxycholic acid but not with cholic acid results in unsaturated hepatic bile. This unsaturation may in part be explained by a decreased hepatic HMG CoA reductase activity.

Adult↗

Biliary lipid composition in patients with porta cirrhosis of the liver.

Fasting duodenal bile was collected under standardized conditions in 10 male patients with stable portal cirrhosis of the liver and in 12 healthy male controls matched for age, body weight, and serum lipid levels. The proportion of cholesterol, expressed as molar percentage of total biliary lipids, was lower in patients with cirrhosis than in controls (4.6 +/- 0.6 versus 6.4 +/- 0.4 molar %, mean +/- S.E.M.; P less than 0.025), whereas the proportions of bile acids and phospholipids were similar in the two groups. The cholesterol saturation of bile was lower in cirrhotic patients (68 +/- 8%) than in controls (94 +/- 7%; P less than 0.025). The contribution of deoxycholic acid to total bile acids was diminished in cirrhosis and that of chenodeoxycholic acid slightly increased. The results suggest that, in spite of the disturbances of bile acid metabolism generally seen in cirrhosis, such patients are not prone to develop cholesterol gallstones.

Bile↗

Effects of treatment with chenodeoxycholic acid on liver microsomal metabolism of steroids in man.

The present investigation was undertaken to evaluate whether treatment of gallstone patients with chenodeoxycholic acid is associated with changes of the hepatic metabolism of steroids. Altogether 37 patients with cholesterol gallstones undergoing cholecystectomy were included in the study. Nine of them had been treated with chenodeoxycholic acid (15 mg/kg/day) for about 8 weeks prior to operation. Two hydroxylations involved in cholic acid biosynthesis, 12 alpha-hydroxylation of 7 alpha-hydroxycholest-4-en-3-one and 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, and the metabolism of a physiological steroid hormone, androst-4-ene-3, 17-dione, were studied in the microsomal fraction of liver homogenates. The 12 alpha-hydroxylase was inhibited about 50%, which is in accordance with a regulatory function of this enzyme. The 25-hydroxylase and the metabolism of androst-4-ene,3, 17-dione were unaffected. It is concluded that chenodeoxycholic acid treatment is not associated with general influences on hepatic steroid metabolism.

Androstenedione↗

Spontaneous dissolution of gallstones. A case report.

Spontaneous dissolution of gallstones is seldom observed. According to present knowledge the maximum spontaneous disappearance rate of radiolucent stones should be less than one per cent per year. The present paper reports on the gradual disappearance of multiple gallstones, probably by dissolution, in an elderly woman. Possible contributing factors are discussed.

Aged↗

Effects of feeding cholic acid and chenodeoxycholic acid on cholesterol absorption and hepatic secretion of biliary lipids in man.

Chenodeoxycholic acid (CDCA), in contrast to cholic acid (CA), reduces cholesterol saturation of bile. The mechanisms for these differences were the object of this study. Investigations were carried out in nine white men; three nonobese subjects and one obese subject were fed a weight-maintenance diet, and five obese patients had a reduced caloric intake for weight reduction. They were given a daily dose of 750-1000 mg CDCA or CA for one month after which they received the other bile acid for another month. The effects of both bile acids on bile acid pool size and hepatic secretion rates of biliary lipids were determined. Total bile acid pools were increased markedly by both CDCA and CA, but to about the same degree for each. Thus, the superior action of CDCA for lowering saturation of bile could not be explained by its effect on the pool sizes of bile acids. On the other hand, hepatic secretion of cholesterol, both during feeding and fasting, was found to be reduced to a greater extent by CDCA than by CA. A theoretical mechanism by which CDCA might lower hepatic outputs of cholesterol is the inhibition of cholesterol absorption. To examine this possibility, cholesterol absorption was estimated by use of an intestinal perfusion technique. No differences were obtained between the two treatment periods for either percentage or net absorption of cholesterol; thus it is unlikely that decreased absorption could account for the reduced cholesterol secretion. Another possibility is that CDCA might affect the interrelations of the three biliary lipids differently than CA. This was explored by measurements of hepatic secretion rates of these lipids. We observed a linear relationship between the secretion rates of bile acids and cholesterol, cholesterol and phospholipids, and bile acids during both treatment periods. However, cholesterol:phospholipid ratios were higher during CA therapy than with CDCA, and they increased still more during fasting in most CA-treated subjects, but not with CDCA. This indicated that there is a marked difference between the two bile acids in the degree of coupling of cholesterol and phospholipids in fasting. We suggest that the reduction in bile sa;uration on CDCA is most likely the result of changes in the interrelations of the different biliary lipids at the site of their secretion and/or inhibition of cholesterol output from the liver because of suppressed cholesterol synthesis in this organ.

Bile↗

Biliary lipid composition in normo- and hyperlipoproteinemia.

The lipid composition of fasting gallbladder bile obtained under standardized conditions was determined in healthy controls and in patients with hyperlipoproteinemia without gallstones. Altogether 23 normolipidemic controls (10 males and 13 females) and 50 hyperlipidemic patients (31 type IIa, 7 type IIb, and 12 type IV) were studied; all were less than 15% overweight. The cholesterol saturation averaged 96 +/- 5% (mean +/- SEM) in the controls, and 10 of them had bile supersaturated with cholesterol. There was no difference between males and females. An increased saturation with age was seen in females. A normal biliary cholesterol saturation (102 +/- 3%) was found in patients with hyperlipoproteinemia type IIa; this was true also for the subgroup with established familial hypercholesterolemia. All patients with hyperlipoproteinemia type IIb and 10 of those with type IV had saturated bile (135 +/- 8% and 121 +/- 6%, respectively). The results suggest an association between certain forms of hyperlipoproteinemia and the development of supersaturated bile. Since fasting gallbladder bile supersaturated with cholesterol is considered to precede gallstone formation, the present results may explain previous findings of an increased prevalence of gallstone disease in patients with hypertriglyceridemia.

Age Factors↗

Prevalence of gallbladder disease in hyperlipoproteinemia.

An analysis of the occurrence of gallbladder disease (ie, cholelithiasis, cholecystitis, cholecystectomy) in 210 consecutive patients with primary hyperlipoproteinemia showed that the prevalence of gallbladder disease was 8%, 18%, and 42% in males with type IIa, IIb, and IV hyperlipoproteinemia, and 22%, 48%, and 72% in the corresponding groups of females. The 40-59-year-old patients were compared to three necropsy series from Malmö, Sweden. The occurrence of gallbladder disease was within normal limits in type IIa and abnormally high in type IV hyperlipoproteinemia. There were no differences with regard to age, body weight, glucose intolerance, or ischemic heart disease between type IV patients with and without GBD. It is suggested that certain forms of disturbances of lipoprotein metabolism are associated with an increased risk for development of gallbladder disease.

Adult↗

Biliary lipid composition during treatment with different hypolipidaemic drugs.

In an attempt to clarify the possible lithogenic effects of commonly used hypolipidaemic drugs, gallbladder bile was obtained from patients with primary hyperlipoproteinaemia before and during treatment with nicotinic acid (n = 13), cholestyramine (n = 19), clofibrate (n = 11), and a combination of cholestyramine and clofibrate (n = 11). Each treatment period was minimum 6 weeks, and standardized dietary conditions were obtained. Both nicotinic acid and clofibrate treatment caused an increase in biliary cholesterol concentration relative to biliary total lipids (bile acids, phospholipids, and cholesterol). During cholestyramine medication the relative cholesterol concentration fell. A combination of cholestyramine with clofibrate medication led to a decrease of bile saturation to pretreatment levels in nine of the eleven subjects. In the other two a further increase in the cholesterol saturation of the bile occurred. Treatment with nicotinic acid and clofibrate but not with cholestyramine is thus probably associated with an increased risk for development of cholesterol gallstones. It is suggested that addition of cholestyramine may be a possible way to prevent the lithogenic effect of clofibrate in patients with hyperlipoproteinaemia when not only hypocholesterolaemic but also hypotriglyceridaemic effects are wanted.

Adult↗

Decreased nitroblue tetrazolium reduction of granulocytes in type IV hyperlipoproteinemia.

NBT reduction of granulocytes was determined in 40 patients with primary hyperlipoproteinemia. The reaction was measured in granulocytes both in the resting state and after stimulation with E. coli, as well as with and without addition of plasma. In 17 patients with type IV hyperlipoproteinemia (endogenous hypertriglyceridemia), the NBT reduction was significantly decreased in all these types of experiments when compared with 12 healthy controls. Sera from hypertriglyceridemic patients decreased NBT reduction of normal granulocytes. Increasing concentration of VLDLs from normolipidemic donors had the same effect. It is suggested that plasma lipoproteins may influence granulocyte function.

Cell Membrane Permeability↗

Hepatic cholesterol metabolism in normo- and hyperlipidemic patients with cholesterol gallstones.

In vivo studies have shown abnormalities in cholesterol and bile acid metabolism in primary hyperlipoproteinemia (HLP). The aim of the present investigation was to determine if the increased production of cholesterol in HLP type IV can be attributed to a correspondingly high level of the hepatic 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity and if the low cholic acid: chenodeoxycholic acid synthesis ratio in HLP type II is due to some hydroxylase deficiency. Liver biopsies from 26 normolipidemic and 25 hyperlipidemic (10 type IIa, 6 type IIb, and 9 type IV) patients undergoing elective cholecystectomy were assayed for HMG CoA reductase activity, 12 alpha-hydroxylase activity, and 25-hydroxylase activity. The HMG CoA reductase activity was normal in HLP type IIa and type IIb and was increased about twice HLP type IV (P less than 0.001). The 12 alpha- and 25-hydroxylase activities were normal in all groups of patients. The results are compatible with a normal cholesterol synthesis in the liver in HLP type II. A reduced 12 alpha- or 25-hydroxylase activity cannot explain the low production of cholic acid relative to chenodeoxycholic acid in this type of HLP. The elevated HMG CoA reductase activity found in the liver of type IV patients may, however, be part of the explanation for the elevated synthesis of cholesterol often seen in these patients.

Adult↗

Effect of cholestyramine on bile acid kinetics in patients with portal cirrhosis of the liver. Evidence of a selective defect in the formation of cholic acid.

The kinetics of cholic acid (C) and chenodeoxycholic acid (CD) were studied in six patients with portal liver cirrhosis. The studies were conducted both before and after 5-6 weeks of treatment with cholestyramine (12 g/day). In keeping with previous observations, the pool size and formation of C showed subnormal values during the pretreatment period, while the production of CD was within normal limits. The pool sizes of C and CD did not change upon treatment with cholestyramine, but the mean total bile acid formation increased by a factor of about 2.5. The ratio between the amounts of C and CD synthesized remained essentially unchanged. Considering the therapeutic response previously observed in normal subjects and in patients with hyper-beta-lipoproteinemia, the present results suggest a selective impairment of the biosynthesis of C in patients with portal liver cirrhosis. It is suggested that the primary defect may reside in the 12alpha-hydroxylase enzyme system.

Aged↗

Effect of chenodeoxycholic acid on serum and biliary lipids in patients with hyperlipoproteinaemia.

1. In order to study the effects of chenodeoxycholic acid on serum and biliary lipids in hyperlipoproteinaemia, chenodeoxycholic acid was administered to seven type IIa, eight type IIb and eight type IV patients in a daily dose of 750 mg (1.9 mmol) for 3 months. 2. The serum concentrations of cholesterol and triglycerides were determined at 4-week intervals: cholesterol remained unchanged whereas triglycerides decreased 15--20%. 3. In 17 patients, biliary lipids were studied. The proportion of chenodeoxycholic acid in the bile increased to about 70%; lithocholic acid and ursodeoxycholic acid increased significantly. 4. Bile saturation with cholesterol decreased and correlated negatively with the proportion of chenodeoxycholic acid in biliary bile acids but positively with serum triglycerides. 5. It is concluded that chenodeoxycholic acid treatment in hyperlipoproteinaemia is associated with parallel fall in serum triglycerides and biliary cholesterol and thus may prove to be a useful adjunct in hypolipidaemic treatment.

Bile↗

Intracutaneous herniation of fat in connection with microangiopathia diabetica.

Three women with diabetes mellitus presented an unusual change in the skin on the distal and acral parts of the extremities, most distinctly on the upper surface of the hands. The surface was raised in small cushions but had the colour of intact skin. The skin felt doughy and swolen on palpation but there was no oedematous pitting. It had been suspected earlier that these skin changes indicated myxoedema or heart disease and the patients had been treated with diuretics. In all three cases, however, histological examinations revealed a more or less reduced, atrophic dermis with here and there an appreciable dislocation of the subcutaneous layer of fat, which with the sweat glands formed an intracutaneous herniation up against the epidermis. These histological changes explained the clinical picture of cushions in the skin. As these patients had diabetes mellitus and the histological picture also included vascular changes of the type associated with a diabetic microangiopathy, it is considered that this form of intradermal herniation of fat is yet another skin change which may be elicited by diabetes mellitis.

Adipose Tissue↗

Hypocalcaemia with zonular cataract due to idiopathic hypoparathyroidism. With a note on the prevalence of severe hypocalcaemia in a health screening.

A 59-year-old woman with idiopathic hypoparathyroidism who had tetany and zonular cataract is described. Twelve years ago she had had a period with cramps and convulsions, followed by an absence of symptoms for several years. Judging from the distance between the opacity of cataract and the surface of the lens, the onset of the cataract was estimated to have occurred 11 years ago and the apparent cessation of cataract development 10 years ago. It is suggested that the absence of hypocalcaemic symptoms during the last 10 years was associated with an increase in serum calcium levels, possibly connected with the onset of menopause. The occurrence of hypocalcaemia was analyzed in a health-screened population of 15 903 persons. Nine of the subjects were found to have a serum calcium level of less than 2.10 mmol/l, giving a prevalence of 0.6%0. None had primary hypoparathyroidism, which illustrates the rarity of this condition.

Cataract↗