Central role of high density lipoprotein in plasma free cholesterol metabolism.

This study was designed to provide direct information on the in vivo metabolism in man of free (unesterified) cholesterol in the major lipoprotein classes. Five human subjects were administered one or two (simultaneous) of the following; [2-(14)C] mevalonic acid, high density lipoprotein (HDL)-free [(14)C] cholesterol, low density lipoprotein (LDL)-free [(14)C] cholesterol, and very low density lipoprotein (VLDL)-free [(3)H]cholesterol. Blood was then obtained at frequent intervals for at least 9 h, and the alpha(HDL) and beta(LDL + VLDL) lipoproteins were quickly separated by heparin-manganese precipitation to prevent ex vivo exchange of free cholesterol. After the administration of [(14)C]mevalonic acid the specific activity (disintegrations per minute/micromole) of free cholesterol in the alpha- and beta-lipoproteins increased for 3 h. During this period the alpha-free cholesterol specific activity was higher than the beta specific activity. After administration of VLDL and LDL labeled with free cholesterol, the alpha-free cholesterol specific activity reached a peak value within 20 min, at which time it was considerably lower than the beta-free cholesterol specific activity. When HDL labeled with free cholesterol was administered, a precursor product relationship was observed between the alpha-free cholesterol (precursor) and beta-free cholesterol (product) specific activities.A multicompartmental model was developed that contained the simplest structure necessary to fit all of the data obtained. The kinetic analysis revealed the presence of extensive exchange (20-85 mumol/min) of free cholesterol between HDL and a tissue pool(s) enriched with newly synthesized free cholesterol. It was found that virtually all (>95%) of the free cholesterol in the beta-lipoproteins (LDL+VLDL) cycles directly through HDL. The free cholesterol in LDL appears to behave in the same fashion as the free cholesterol in VLDL. The results show that there are marked differences in the kinetic behavior of the free cholesterol fractions of alpha- and beta-lipoproteins. There is extensive recycling of free cholesterol between HDL and tissue pools, and between HDL and the beta-lipoproteins; this recycling has been quantitated. The findings support the view that in vivo, the free cholesterol in HDL plays a central role in exchange reactions and in the vascular-tissue cholesterol transport system.

Spontaneous peritonitis due to Hemophilus influenzae in an adult.

Hemophilus influenzae, usually pathogenic in the pediatric population, caused septicemia and peritonitis in the cirrhotic adult described here. Susceptibility to this unusual adult pathogen was perhaps related to liver disease or corticosteroid treatment. This organism has not previously been associated with the syndrome of spontaneous bacterial peritonitis in an adult.

Acute viral hepatitis with bridging hepatic necrosis. An overview.

Bridging hepatic necrosis in the setting of acute viral hepatitis (BHN/AVH) represents an enigmatic syndrome inasmuch as its incidence, significance, course, and therapeutic response have not been clearly defined. It has been thought that this histologic finding carries a high risk of early mortality or evolution to chronic active hepatitis and/or cirrhosis. The data are sparse, and largely based on retrospective studies in selected populations. Steroids have not proved to be effective thus far, while drugs used in other forms of serious liver disease (eg, penicillamine, colchicine) have not been tried. A recent prospective study indicates that BHN/AVN may be a far more benign entity than was previously suspected. Further prospective studies are needed to clarify the significance of this lesion as well as the need for and response to medical therapy.

Duodenal ulcer disease: a fresh appraisal.

There have been remarkable recent advances in knowledge about duodenal ulcer, a disease which may be spontaneously disappearing. Multiple physiologic defects have been found including increased numbers of parietal cells and their increased sensitivity to gastrin, excessive gastrin release after food intake, decreased inhibition of gastrin release by low antral pH, more rapid gastric emptying, and, possibly, impaired duodenal mucosal resistance to acid. Antacid and diet therapies have been subjected to scientific scrutiny and their respective roles in the therapy of the duodenal ulcer are now better defined. New drugs have been developed which strongly inhibit gastric acid secretion in man--the recently marketed histamine H2-receptor antagonist, cimetidine, as well as chemically modified prostaglandins. Clinical trials have shown cimetidine to be effective in healing duodenal ulcers and free of significant side effects with short-term usage. Its role in the prevention of ulcer recurrence is presently being evaluated. A new operation for duodenal ulcer has been introduced which shows great promise following pilot studies and some randomized trials. Only the parietal cell containing portion of the stomach is denervated. Basal and stimulated gastric acid secretion are markedly inhibited while gastric motility is unimpaired. This operation thus eliminates the need for a drainage procedure or distal antral resection and decreases the incidence and severity of undesirable side effects associated with earlier operations for duodenal ulcer.