Search

A syndrome of portal hypertension with hemorrhagic ascites was developed in a 44-year-old patient, 2 years after he had been diagnosed as having a chronic lymphatic leukemia. The study of the patient, including two liver biopsies and a laparoscopy, excluded the existence of another hepatic or extrahepatic associated condition. The clinical course of the patient was rapidly fatal progressive in spite of the cytostatic therapy, and he died as a result of an acute liver failure. The autopsy confirmed the absence of vascular occlusions in the suprahepatic veins or in the vena porta. The liver showed, in contrast to the findings of previous biopsies and laparoscopy, an evident fibrotic pattern.

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 degrees C in human serum (d greater than 1.215) that had been prelabelled with [4-14C]cholesteryl oleate or [1,2-3H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. . pmol-1 (46 d.p.m. . ng-1) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction.

Low density lipoprotein (LDL) undergoes qualitative changes when incubated with endothelial cells. Changes in LDL induced by cultured human endothelial cells were associated with release of substances reacting to thiobarbituric acid; they were prevented by addition of EDTA. Modification of LDL by human endothelium, therefore, appears to involve lipid peroxidation. Proneness of LDL to this process was indicated by its occurrence, to a smaller extent, on incubation in the absence of endothelium. Lipid peroxidation of LDL altered its electrophoretic mobility. Modified LDL, but not native LDL, was readily catabolised by human macrophages. Conditioning by human endothelium increased the rate of fractional catabolism of LDL in rabbits. If lipid peroxidation of LDL takes place in vivo it may promote conversion of macrophages to lipid-laden foam cells in the developing atheromatous plaque.

Variation in plasma cholesterol in normal populations underlies a 2-5 fold range of risk of coronary heart disease. The metabolic basis of this variation was studied in a healthy population recruited from a general-practice list. Compared with men in the modal decile of plasma cholesterol, those in the top decile maintained their high levels by overproduction of low-density lipoprotein (LDL). Men in the bottom decile of plasma cholesterol had low levels of LDL, resulting chiefly from a greater rate of fractional catabolism of this lipoprotein; and blood mononuclear cells from men in the bottom decile catabolised LDL more rapidly in vitro than did cells from other men. Intake of dietary lipids by men in the top, modal, and bottom deciles did not differ significantly. Different mechanisms appear to underlie high and low levels of plasma cholesterol in a normal population.

Six patients (four women and two men) with mild to moderate hypercholesterolemia, but with no clinical evidence of the disease being monogenic familial hypercholesterolaemia and who, over the previous 3 months on a rigidly controlled hypolipidaemic diet therapy, showed no reduction in plasma cholesterol levels, were recruited into a study to assess the metabolic effects of Pirozadil, a new nicotinic acid derivative. After a 3 month treatment period, a significant reduction in plasma cholesterol from 299.8 +/- 31.2 mg/dl (mean +/- SD) to 256.8 +/- 18.1 mg/dl (P less than 0.02) and Low Density Lipoprotein (LDL) cholesterol from 211.7 +/- 44.9 mg/dl to 168.8 +/- 19.0 mg/dl (P less than 0.05) was observed. Although there was a trend toward decreased plasma and Very Low Density Lipoprotein (VLDL) triglyceride, the differences did not reach statistical significant. High Density Lipoprotein (HDL) cholesterol was unchanged. The drug was well tolerated with no side effects noted. To assess the mode of action, autologous125I-labelled LDL was injected and apoprotein B (apo B) kinetic parameters were measured; production rate (PR) and fractional catabolic rate (FCR). An in vitro measurement of the in vivo catabolism (LDL-apo B receptor activity in freshly isolated lymphocytes) was also measured pre- and post-treatment. The pharmacological intervention resulted in a significant decrease of 19.9% in PR from 10.5 +/- 1.81 mg/kg/d to 8.41 +/- 1.13 mg/kg/d (P less than 0.05) while the FCR remained relatively unchanged (0.260 +/- 0.042 vs 0.248 +/- 0.040 pools/d) as did the LDL receptor activity (78.2 +/- 20.9 vs 69.3 +/- 21.4 ng LDL/mg cell protein/hr).(ABSTRACT TRUNCATED AT 250 WORDS)

With puromycin aminonucleoside-induced nephrotic syndrome (NS) in rats, twofold elevated levels of lipoproteins were observed. These levels were not related to proteinuria or to plasma albumin levels. Ultrastructural lesions induced in the kidneys by puromycin aminonucleoside were consistent with NS, while there was little or no hepatic involvement. Apolipoprotein B (apo B) kinetic measurements using homologous 125I-labeled low density lipoproteins (LDL) demonstrated a higher synthetic rate in nephrotic rats relative to controls (6.18 +/- 1.86 micrograms x g-1 x d-1 v 3.94 +/- 0.66 micrograms x g-1 x d-1 respectively, P less than .005), while the fractional catabolic rate was only marginally reduced (1.64 +/- 0.28 pools x day-1 in NS v 1.83 +/- 0.37 pools x day-1 in controls, P less than 0.4). These results indicate that in rats with experimentally induced NS, the expanded apo B-LDL pool results from increased synthesis of this apoprotein while no significant role can be ascribed to alterations in its catabolism. These data are consistent with our preliminary findings in NS in humans.

Serum high-density lipoprotein cholesterol (HDL-C) has been determined in 85 patients with peripheral vascular disease (PVD) and in 72 healthy control subjects. HDL-C levels were significantly decreased in patients with PVD. Considering other vascular risk factors as diabetes mellitus, smoking and hypertension, there were no differences in HDL-C levels. Twenty-three patients received heparin as treatment, this subgroup showed a HDL-C levels higher than patients who were not under heparin therapy. The possible clinical implications of these facts are discussed.

Concentrations of apoprotein A in whole serum, and cholesterol and phospholipids concentrations in the high-density lipoprotein fraction of serum were measured after the precipitation of low-density and very-low-density lipoproteins with sodium phosphotungstate-Mg2+ in 23 patients with liver cirrhosis, 19 patients with extrahepatic biliary obstruction, and 20 healthy control subjects. Patients with cirrhosis and cholestasis showed approximately one-half as much cholesterol and apoprotein A in the nonprecipitable high-density lipoprotein fraction as normal subjects did. High-density lipoprotein phospholipids concentrations in those patients were normal or slightly increased, however, which is about double what one would expect from the apoprotein A and cholesterol content.

The serum levels of cholesterol bound to high density lipoproteins (HDL-C) were determined by the heparin-manganese chloride precipitation method in 306 subjects, 182 male with ages ranging from 11 to 81 years, and 124 female with ages ranging from 7 to 78 years. Twenty six subjects belonged to a lacto-vegetarian community, while the remaining 280 were healthy volunteers, factory workmen sampled during a regular check-up, and either outpatients or inpatients being evaluated for minor illnesses or minor surgery. None of the subjects had arteriosclerosis or a metabolic disease and, with the exception of the lacto-vegetarians, they were all consuming a normal diet. HDL-C concentrations varied very little among the different age groups. Females had HDL-C values slightly superior to those of males. No significant differences were found between smokers and non-smokers, alcohol drinkers and non-drinkers, and regularly exercising and sedentary people. HDL-C concentrations were independent of total cholesterol and triglyceride levels. Females under oral contraceptive treatment had lower HDL-C levels than control females, but the differences were not statistically significant. Compared with age and sex-matched controls, the lactovegetarians showed similar HDL-C concentrations.

An etiologic study was made of 107 cases of granulomatous hepatitis which were observed in a Department of Internal Medicine between January, 1971 and December, 1977 (excluding the hepatobiliary diseases). The most common etiology was tuberculosis (30 cases, 28 percent) followed by sarcoidosis (19 cases, 17.7 percent), Mediterranean exanthematous fever (13 cases, 12.1 percent), brucellosis (8 cases, 7.4 percent) typhoid fever (7 cases, 6.5 percent) and the idiopathic forms (8 cases, 7.4 percent). A lower rate of incidence was among Hodgkin's disease, toxoplasmosis, adenocarcinomas, leprosy, and those of unknown etiology, classified in this way because the study and follow-up of the patients could not be completed. There were, moreover, individual cases caused by mononucleosis, BCG reaction, hypogammaglobulinemia, celiac disease, and temporal arteritis. From a clinical point of view 50 percent of the patients had hepatomegaly and moderate disturbance of the liver enzymes. The most important enzymatic increases were detected in the cases caused by brucellosis; in the cases which were secondary to sarcoidosis the liver enzymes were normal. A comparison is established between the etiologic incidence of the present series and of others published in the literature. The causes and diagnostic problems of this type of lesion are discussed.

In this series, the commonest aetiology was tuberculosis (30 cases, 28%), followed by sarcoidosis (18 cases, 17,7%), mediterranean fever (Olmer's disease) (13 cases, 12,1%), brucellosis (8 cases, 7,4%), typhoid fever (7 cases, 6,6%) and idiopathic forms (8 cases, 7,4%). These were followed by Hodgkin's disease, toxoplasmosis, adenosarcoma, and leprosy. Finally, there were single cases due to infectious mononucleosis, B.C.G. reaction, hypogammaglobulinaemia, coeliac disease and temporal arteritis. Half of the patients had hepatomegaly and an increase, in general moderate, in hepatic enzymes (transaminases, alkaline phosphatase). The highest enzyme levels were seen in cases of brucellosis, hepatic enzymes being normal in patients with sarcoidosis.