The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.

Atherogenesis: a postprandial phenomenon.

In healthy individuals, acute changes in cholesterol intake produce modest changes in plasma cholesterol levels. A striking exception occurs in sitosterolemia, an autosomal recessive disorder characterized by increased intestinal absorption and decreased biliary excretion of dietary sterols, hypercholesterolemia, and premature coronary atherosclerosis. We identified seven different mutations in two adjacent, oppositely oriented genes that encode new members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family (six mutations in ABCG8 and one in ABCG5) in nine patients with sitosterolemia. The two genes are expressed at highest levels in liver and intestine and, in mice, cholesterol feeding up-regulates expressions of both genes. These data suggest that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis.

https://science.sciencemag.org/content/sci/290/5497/1771.full.pdf

Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters

A case is described of presumed quinidine hepatotoxicity, characterized by the development of fever, abnormal serum transaminase values, which improved after cessation of the drug but recurred after a challenge dose, and centrizonal hepatocellular necrosis detected on liver biopsy. Morphological changes on electron microscopy, consistent with a drug reaction, are also described. Pertinent features of previous case reports are analyzed, and the histological findings by light microscopy of the present and past cases are discussed. It is suggested that the development of unexplained fever within 1 month of quinidine administration should lead to consideration of possible hepatotox­ icity.

https://www.gastrojournal.org/article/S0016-5085(76)80326-5/pdf

A report of a case and review of the literature

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines

The causes of sudden and unexpected death in 29 highly conditioned, competitive athletes, ages 13–30 years, are summarized. Sudden death occurred during or just after severe exertion on the athletic field in 22 of the 29 athletes. Structural cardiovascular abnormalities were identified at necropsy in 28 of the 29 athletes (97%), and in 22 (76%) were almost certainly the cause of death. The most common cause of death in this series was hypertrophic cardiomyopathy, which was present in 14 athletes. Other cardiovascular abnormalities that occurred in more than one athlete were anomalous origin of the left coronary artery from the right (anterior) sinus of Valsalva, idiopathic concentric left ventricular hypertrophy, coronary heart disease and ruptured aorta. Cardiac disease was suspected during life in only seven of the 29 patients, and in only two of the seven was the correct diagnosis made clinically. Hence, in this series of young athletes, sudden death was usually due to structural cardiovascular disease, and hypertrophic cardiomyopathy was a frequent cause of sudden death; atherosclerotic coronary heart disease was relatively uncommon.

Sudden death in young athletes

Little is known about the structure of athletes' hearts of anatomic variations associated with training. Echocardiograms of 56 active athletes were obtained. Mean left ventricular end-diastolic volume and mass were increased in athletes involved in isotonic exercise, such as swimming (181 ml, 308 g) and running (160 ml, 302 g), compared with controls (101 ml, 211 g); wall thickness was normal (less than or equal to 12 mm). Athletes involved in isometric exercise, such as werstling and shot putting, had normal mean left ventricular end-diastolic volumes (110 ml, 122 ml), but increased wall thickness (13 to 14 mm) and mass (330 g, 348 g). Thus, athletes participating in isotonic exercise had increased left ventricular mass with cardiac changes similar to those in chronic volume overloads. Athletes participating in isometric exercise had increased left ventricular mass with cardiac changes similar to those in chronic pressure loads, recognizing greater left ventricular mass and volume in well-trained athletes aids in interpreting values deviating from "normal" limits.

Comparative Left Ventricular Dimensions in Trained Athletes

The clinical and biochemical features of type III hyperlipoproteinemia are described in 49 patients from 23 to 70 years of age. An increase in very low-density lipoproteins (VLDL) of abnor...

The biochemical, clinical, and genetic features of type III hyperlipoproteinemia.

Two current definitions of type III hyperlipoproteinemia, "floating beta" lipoproteins and an estimate of the relative content of cholesterol and triglyceride in lipoproteins of density le...

Type III hyperlipoproteinemia: an analysis of two contemporary definitions.

The cytotoxic action of lymphocytes upon cells bearing alloantigens to which they are sensitized is inhibited by agents that elevate intracellular amounts of 3′:5′-cyclic AMP: prostaglandin E1, cholera toxin, and theophylline. Cholinergic agents, added in the range of 1 to 100 pM, enhance cytotoxicity, an effect that is blocked by atropine. Because cholinergic agents elevate cyclic GMP in other in vitro systems, these findings suggest that the cytotoxic process effected by sensitized lymphocytes is a secretory phenomenon modulated by cyclic AMP and cyclic GMP.

Alteration of the Cytotoxic Action of Sensitized Lymphocytes by Cholinergic Agents and Activators of Adenylate Cyclase

We studied 100 consecutive patients to evaluate the potential effect of platelet active and antithrombotic agents prescribed preoperatively on bleeding complications after coronary-artery ...

Joel Morganroth

Papers

Comparative Left Ventricular Dimensions in Trained Athletes

The biochemical, clinical, and genetic features of type III hyperlipoproteinemia.

Type III hyperlipoproteinemia: an analysis of two contemporary definitions.

Alteration of the Cytotoxic Action of Sensitized Lymphocytes by Cholinergic Agents and Activators of Adenylate Cyclase

Aspirin- and coumadin-related bleeding after coronary- artery bypass graft surgery.