G. Dewey Dunn

Fatty liver: biochemical and clinical considerations.

Fatty liver may be defined as an acctJmulation of lipid, consisting principally of triglycerides in most cases, which exceeds 5~ of the liver weight. The clinical importance of excess fat varies with its cause and quantity. In some instances (ie, obesity) it may be of little consequence, whereas in others (ie, fatty liver of pregnancy) it may lead to hepatic failure and death. The aim of this brief review is to summarize the main clinical and biochemical features of the principal conditions associated with significant fatty infiltration of the liver as the primary pathologic finding.

Bacteremia with Upper Gastrointestinal Endoscopy

Fifty patients undergoing upper gastrointestinal fiberoptic endoscopy were studied prospectively for the development of bacteremia by aerobic and anerobic blood cultures obtained before, during, and at 5 and 30 minutes after the procedure. Forty-six patients were culture negative; four had positive cultures at 5 or 30 minutes after the procedure, or at both times. The level of bacteremia as estimated by pour plates was very low. Bacteremia did not correlate with the performance of biopsy or the type of mucosal abnormality found. It is concluded that only very high-risk patients should receive antimicrobial prophylaxis before this procedure. The minor risk of this low-level bacteremia should not be considered a contraindication to the performance of upper gastrointestinal endoscopy.

Effects of several common long chain fatty acids on the properties and lipid composition of the very low density lipoprotein secreted by the perfused rat liver

1. Livers from normal fed male rats were perfused in vitro with a bloodless medium which contained intially 3% bovine serum albumin and 100 mg% glucose. Albumin alone, or myristate (14 : 0), palmitate (16 : 0), palmitoleate (16 : 1), stearate (18 : 0), oleate (18 : 1), or linoleate (18:2) was infused at a constant rate (496 mumol/4 h), as a complex with albumin, during the experiment. 2. The very low density lipoprotein secreted by the liver after infusion of unsaturated fatty acids (16 : 1, 18 :1, 18 : 2) has a faster rate-zonal mobility in the ultracentrifuge and is, therefore, probably a larger particle with fewer moles of phospholipid and cholesterol relative to triacyglycerol (triacyglycerol/phospholipids/cholesterol = 100/25.1/16.4) than the very low density lipoproteins produced after infusion of saturated (14 : 0, 16 : 0, 18 : 0) fatty acids (triacyglycerol/phospholipids/cholesterol = 100/30.1/19.1). The molar ratio of phosphoipids/cholesterol of the very low density lipoprotein was similar regardless of which fatty acid was infused. The predominant fatty acid of the very low density lipoprotein or hepatic triacyglycerol, in all cases, was the infused acid. 3. We conclude that free fatty acid regulates the quantity and proportions of triacyglycerol, phospholipids, and cholesterol secreted by the liver in the very low density lipoprotein, and therefore, may secondarily influence concentrations of lipids in the very low density lipoprotein and other plasma lipoproteins circulating in vivo.

Characterization of the hyperlipidemia in guinea pigs induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Treatment of adult male guinea pigs with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 6.2 nmol (2.0 μg)/kg body wt, induces a marked hyperlipidemia characterized by a 19-fold increase in very low density lipoproteins (VLDL) and a 4-fold increase in low-density lipoproteins (LDL) compared to pair-fed control animals. VLDL from TCDD-treated animals were similar in size and electrophoretic mobility to VLDL from pair-fed control animals, but they contained less cholesteryl ester and an altered pattern of C apoproteins on sodium dodecyl sulfate-polyacrylamide gels. LDL from TCDD-treated animals were larger than LDL from pair-fed controls and contained more phospholipid and less protein than LDL from pair-fed control animals. In addition, LDL from TCDD-treated animals contained increased amounts of apoprotein C as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No change in the concentration or properties of serum high-density lipoproteins was observed. Serum free fatty acids, triglycerides, and cholesteryl esters from TCDD-treated animals were enriched in linoleic acid (18:2), a principal fatty acid of adipose tissue. This suggests that mobilization of adipose tissue fatty acids in TCDD-treated animals may lead to increased hepatic lipoprotein production. However, weight-paired control animals did not become hyperlipidemic. Thus, in addition to mobilizing adipose tissue fatty acids, TCDD may alter the relative rates of anabolic and/or catabolic processes controlling serum VLDL and LDL concentrations in the guinea pig.

Malignant fibrous histiocytoma of the liver

A 59-yr-old man was admitted to the hospital for evaluation of right upper quadrant pain, anorexia, weight loss, and low-grade fever of 2-mo duration. During his evaluation, an abnormal liver ultrasound and computed tomography scan demonstrated what proved to be an avascular hepatic lesion. At surgery, the diagnosis of malignant fibrous histiocytoma was established. We present herein our findings of what we believe to be the first reported study of malignant fibrous histiocytoma of the liver.

Effects of caffeine on plasma free fatty acids, urinary catecholamines, and drug binding

The effects of caffeine (250 mg orally) on plasma free fatty acids (FFA), urinary catecholamines, and drug binding were studied in 16 normal subjects (six men, five women on oral contraceptives, and five women not on oral contraceptives). FFA doubled 1 hr after caffeine, and remained elevated for at least 4 hr, with elevation of each FFA. Urinary excretion of epinephrine and dopamine increased (p < 0.05) in the first 2 hr, returning to baseline in the next 2 hr. Plasma binding of chlordiazepoxide, diazepam, and propranolol was estimated in each of the hourly plasma samples after caffeine; there was no change in percent unbound drug in any of the samples. In vitro addition of oleic acid to plasma samples of four subjects caused a step‐wise increase in percent unbound fraction of all three drugs whereas in vitro addition of caffeine did not further alter drug binding. In our study circulating plasma FFA and urinary catecholamine levels were elevated after caffeine ingestion. In spite of a rise in FFA, there was, however, no change in plasma binding of chlordiazepoxide, diazepam, or propranolol.

Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: acute experiments in rats fed safflower oil.

Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18∶2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16∶0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoprotein phospholipids were enriched with 18∶2 more than were the hepatic phospholipids. Furthermore, the percentage of 18∶2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18∶2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low density lipoprotein was 100∶42.0∶22.1∶44.5 in the control group and 100∶35.4∶17.8∶19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver.

Effects of a mixture of a saturated with an unsaturated fatty acid on secretion of the very low density lipoprotein by the liver

Abstract Palmitic acid (16:0) and palmitoleic acid (16:1), as the complex with bovine serum albumin, were infused at rates of 62 and 124 μmoles/hr into an albumin-buffer medium perfusing livers isolated from normal fed male rats. In other experiments, equimolar mixtures (124 μmoles/hr, total) of 16:0 + 16:1, or myristate (14:0) + 16:1 were infused. The output of triglyceride when 16:1 was infused was greater than when equivalent amounts of 14:0 or 16:0 were infused; output with equimolar mixtures of 14:0 and 16:1, or 16:0 and 16:1 was intermediate between that of saturated and unsaturated fatty acids alone. Rate-zonal mobility of the VLDL in the ultracentrifuge was more rapid as the quantity of 16:1 available to the liver increased, but did not change with increasing amounts of 16:0. The rate-zonal mobility of the mixtures of 14:0 and 16:1, or of 16:0 and 16:1, was not different than that of 16:1 alone. The ratios of phospholipid and cholesterol relative to triglyceride in the VLDL decreased with increasing output of triglyceride and with unsaturation of the fatty acid. Ratios resulting from mixtures of the fatty acids appeared to be in an intermediate position. The composition and properties of the secreted VLDL clearly are dependent on the structure and quantity of FFA available to the liver; with mixtures of saturated and unsaturated fatty acids, the unsaturated fatty acid seems to exert a dominant effect.

Rectal Ulcers and Chronic Renal Failure

Excerpt To the editor: We read with interest the report of Goldberg and coworkers ( 1 ) about rectal ulcers in patients with chronic renal failure. We recently saw a 55-year-old black man with end-...