suMMARY During the period 1955 to 1974 inclusive, 826 patients developed Crohn's disease and were registered citizens of Stockholm County at the time of definite diagnosis. These patients were followed up and investigated with reference to the occurrence of and outcome after treatment for anal fistulae. These fistulae were recorded in 184 patients (23 %/.). The incidence of anal fistulae increased the further distally the intestinal lesion was located. Healing followed local operation for anal fistula before curative intestinal resection in approximately 60% of the patients with small intestinal and combined ileocolic disease. However, patients with colonic Crohn's disease did not heal after such treatment. When curative intestinal resection was the primary procedure, 47 % of the patients healed spontaneously. Small intestinal and combined ileocolic disease was associated with a good prognosis-90 % were healed at follow-up,
Inhibition of hepatic HMG-CoA reductase by pravastatin results in an increased expression of hepatic LDL receptors, which explains the lowered plasma levels of LDL cholesterol.
A B S T R A C T This investigation was undertaken inorder to (a) characterize the postprandial inflow of individual bile acids to the liver and (b) determine if peripheral venous bile acid levels always adequately reflect the portal venous concentration, or if saturation of hepatic bile acid uptake can occur under physiological conditions. In five patients with uncomplicated cholesterol gallstone disease, the umbilical cord was cannulated during cholecystectomy, and a catheter was left in the left portal branch for 5 to 7 d. The serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid in portal venous and systemic circulation were then determined at intervals of 15 to 30 min before and after a standardized meal.A highly accurate and specific gas chromatographic/ mass spectrometric technique was used.The sum of the fasting concentrations of the three bile acids averaged 14.04±4.13 Amol/liter in portal venous serum, and 2.44±0.31 Amol/liter in peripheral venous serum. The estimated hepatic fractional uptake of cholic acid was -90%, and those of chenodeoxycholic acid and deoxycholic acid were 70-80%. This resulted in an enrichment of systemic bile acids in the dihydroxy bile acid species. In response to a standardized meal, portal venous bile acid concentrations increased two-to sixfold, with a peak seen 15-60 min after the meal. The maximum postprandial portal venous bile acid concentration averaged 43.04±6.12,umol/liter, and the corresponding concentration in peripheral serum was 5.22±0.74 A.mol/liter. The estimated fractional uptakes of the individual bile acids were not affected by the increased inflow to the liver. The peripheral venous concentrations of individual as
The heparin-sensitive binding of '2SI-labeled low-density lipoprotein (LDL) to homogenates from 18 different normal human tissues and some solid tumors was determined. The binding to adrenal and liver homogenates fulfilled criteria established for the binding of LDL to its receptor-namely, (i) saturability, (ii) sensitivity to proteolytic destruction, (ii) inhibition by EDTA, and (iv) heat sensitivity. When the binding of '2-I-labeled LDL was assayed at a constant concentration (50 jig/ml), the adrenal gland and the ovary had the highest binding of normal tissues. The highest binding per g oftissue overall was obtained in homogenates of a gastric carcinoma and a parotid adenoma. When the weights ofthe parenchymatous organs were considered, the major amount of LDL receptors was contained in the liver. To study the possible regulation of hepatic LDLreceptor expression, 11 patients were pretreated with cholestyramine (8 g twice a day for 3 weeks). Increased binding activity (+105%, P < 0.001) was obtained in homogenates from liver biopsies from the cholestyramine-treated patients as compared with 12 untreated controls. It is concluded that the liver is the most important organ for LDL catabolism in humans and that the receptor activity in this organ can be regulated upon pharmacologic intervention. Further studies are needed to confirm the possibility that certain solid tumors can exhibit high numbers of LDL receptors.Elevated levels of plasma cholesterol are associated with an enhanced risk for the development of coronary heart disease (1). The major fraction of cholesterol in human plasma is contained within low density lipoproteins (LDL), and the reduction of this lipoprotein fraction by pharmacologic intervention has been shown to decrease the incidence of coronary events (2). The concentration of LDL in plasma is determined by the balance between the synthesis (occurring from the metabolism of very low density lipoproteins) and the catabolism of the lipoprotein particle. Of particular importance for the clearance of LDL is the presence of specific, high-affinity cell-surface receptors for these lipoproteins, the LDL receptors (3, 4).The LDL receptor, originally described by Goldstein and Brown (5) in cultured human fibroblasts, has been demonstrated in a variety of cell types (3). After binding to its receptor, the LDL particle is internalized by endocytosis and transported to lysosomes, where it is degraded to free cholesterol and amino acids. The number of LDL receptors is regulated according to the cellular demand for cholesterol (3, 4). Thus, cells synthesizing steroid hormones and rapidly growing cells have high numbers of LDL receptors (3). An increased expression of LDL receptors has also been described in certain forms of leukemia (6, 7). A specific metabolic abnormality exists in the genetic disease familial hypercholesterolemia, where functional LDL receptors are absent (homozygotes) or are produced in reduced numbers (heterozygotes) (8).Animal studies have indicated that the adrenal cortex a...
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