Biomedical subjects
Publications and source records attributed to H J Fallon.
Approximately 4 million people in the United States are affected with chronic hepatitis C--20%-25% of whom will develop cirrhosis. Determination of the stage of disease and extent of cirrhosis requires liver biopsy. In cirrhotic patients, regular screening for hepatocellular carcinoma is indicated.
Interferon-alpha is the only approved and effective treatment for hepatitis C. Psychiatric side effects are common and have frequently required a decrease in dose or discontinuation of therapy. We here report a case of interferon-alpha-induced depression in a 40-yr-old man with hepatitis C successfully treated with the antidepressant fluoxetine, which allowed completion of interferon treatment.
Explore the source record for details and available documents.
Changes in medical practice and in the financing of hospital care have resulted in a narrowing spectrum of adult medical illness among hospitalized patients. Residency training based primarily in the hospital underemphasizes many diseases and disorders that are treated exclusively at ambulatory sites. Curriculum modifications should allow for increased training time for residents in the ambulatory care setting. Reducing clinical inpatient service demands on residents and alleviating the attendant stress will allow more time for such educational experiences. The Medical College of Virginia has had recent experience with three modifications to the curriculum, which are intended to accomplish these ends: a specialized unit for inpatient services, which is not staffed by interns; a reorganization of the daily inpatient care schedule; and a modified "night float" team.
Explore the source record for details and available documents.
STUDY OBJECTIVE: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. SETTING: Four university teaching hospitals. PATIENTS: We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32, calculated using the formula: 4.6 (prothrombin time - control time) + serum bilirubin [in mumol/L]/17.1. Fifty-nine patients (89%) completed the study. Two patients withdrew from the trial. The other 64 patients were hospitalized for the duration of the trial; however, treatment was discontinued in 5 patients because of potential drug toxicity. INTERVENTIONS: Patients were randomly assigned to receive either methylprednisolone (32 mg) or placebo within 7 days of admission. Treatment was given for 28 days. The doses were then tapered over 2 weeks and discontinued. MEASUREMENTS AND MAIN RESULTS: The endpoint of the study was death. Of the 31 recipients of placebo, 11 (35%) died within 28 days of randomization compared with 2 (6%) of the 35 patients given methylprednisolone (P = 0.006). The 95% CI for the difference in mortality was 12% to 70%. In the patients with spontaneous hepatic encephalopathy at entry, 9 of 19 recipients of placebo died (47%) compared with 1 (7%) of the 14 patients given methylprednisolone (P = 0.02). The 95% CI for the difference in mortality was 14% to 66%. The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables (P = 0.004). CONCLUSIONS: Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value.
An unresolved controversy is whether exposure to organic solvents in the workplace causes hepatotoxicity. From a medical surveillance study of 289 printing factory employees who were exposed primarily to toluene, we identified eight workers who had persistently abnormal serum transaminase and/or alkaline phosphatase values. The eight men were generally healthy and gave no history of taking medications or of drinking ethanol to excess. None was obese or diabetic. Six patients had hepatomegaly based on physical examination. All eight had mild elevations (less than 2 to 3 times the upper value of normal) of serum transaminases [alanine (ALT) and aspartate aminotransferase (AST)]. However, there was a marked increase in the ratio of ALT/AST (mean = 1.61). In each case, liver biopsy revealed mild, pericentral fatty change. Our results, consistent with those previously published by some others, suggest that pericentral fatty liver with mild "reactive hepatitis" is the most likely diagnosis in workers exposed to solvents for whom common causes of mild liver test abnormalities have been excluded. An increased ALT/AST ratio may represent a convenient, previously unrecognized indicator of this condition.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Triacylglycerol lipase activities of homogenates and subcellular fractions of rat liver were measured under optimal conditions at pH 7.5 using emulsified tri[1-14C]oleoylglycerol as substrate. Twenty-four hr after administration of streptozotocin, hepatic alkaline lipase activity was 39% of normal, and this lower level of activity was observed at 72 hr and 7 days, after streptozotocin injection. After 24 hr of starvation, lipase activity also was significantly lower (35%) than normal. Insulin (35 U regular/kg body weight) had no acute (90 min) effect on the hepatic lipase activity of either normal or diabetic rats. Chronic insulin administration (4 subcutaneous injections of 10 U protamine zinc insulin/kg at 16-hr intervals) to normal rats provoked a 40% increase in hepatic lipase activity. Diabetic rats given the same insulin treatment showed lipase activity that was significantly higher (155%) than normal. Lipase activity fell to 65% of normal when insulin was withheld (32 hr) from diabetic rats given chronic insulin therapy. Intracardial injection of glucagon (1 mg/kg) into normal rats had no acute (30 min) effect on hepatic alkaline lipase activity. Hepatic alkaline lipase activity varied independently from the concentrations of either glucose or triacylglycerol in the plasma. However, there was an apparent negative correlation between this lipase activity and the concentration of fatty acids in the plasma; lipase activity was highest when fatty acid concentrations were lowest, and lowest when fatty acid concentrations were elevated. From these data we conclude: 1) changes in hepatic alkaline lipase activity ware provoked by chronic, but not acute, alteration of the hormonal and metabolic status of the rat, and 2) changes in hepatic alkaline lipase activity may be mediated through changes in the levels of circulating fatty acids presented to the liver, but the effect is not an immediate one.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Intestinal mucosal microsomes from several animal species (non-fasted) were used to study the formation of glycerolipids from sn-[1,3-14C]glycerol 3-phosphate and palmitoyl-CoA. Rates of glycerolipid biosynthesis were species dependent, since mouse and rat were quite low compared to hamster, guinea pig and man. Under the usual incubation conditions, guinea pig intestinal microsomes formed primarily phosphatidic acid (85-90%). However, when Mg2+ was added to incubations containing intestinal microsomes prepared in the presence of 5 mM EDTA, there was a marked increase in neutral lipid biosynthesis (5-10-fold). These results suggest that intestinal microsomes contain mg2+-dependent phosphatidate phosphohydrolase (EC 3.1.3.4) which is involved in glycerolipid biosynthesis. All divalent cations studied increased sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) activity; however, Ca2+, Ba2+, Zn2+, Cd2+, Ni2+, and Mn2+ antagonized the Mg2+-dependent rise in neutral lipid formation. In all cellular preparations studied, the ratio of neutral lipid (diacylglycerol + triacylglycerol) to total lipid (phosphatic acid + neutral lipid) was low, suggesting that phosphatidate phosphohydrolase may be rate limiting in intestinal neutral glycerolipid biosynthesis.
The effect of acute and chronic ethanol intake on hepatic glycerolipid biosynthesis in the hamster was studied by in vivo and in vitro techniques. The results were compared with those from control hamsters receiving isocaloric amounts of glucose. Both chronic and acute ethanol intake elevated serum and hepatic triglyceride concentrations and induced a rapid rise in the capacity of neutral glycerolipid formation from sn[1,3-14C]glycerol-3-phosphate by hamster liver homogenate and microsomal fractions. Ethanol intake also produced a corresponding increase in the incorporation of [1,3-14C]glycerol into hepatic neutral glycerolipids by the intact animal. The ethanol-induced rise in the capacity of neutral glycerolipid production by liver as measured in vivo and in vitro correlated well with an increase in hepatic phosphatidate phosphohydrolase activity. Therefore, the rise in hepatic and serum triglyceride levels associated with ethanol intake may be explained in part by an increase in the activity of the enzyme.
Explore the source record for details and available documents.