No abstract

Severe liver failure developed in three chronic alcoholics after they ingested acetaminophen for therapeutic reasons. The clinical course was characterized by SGOT levels of 5,000 to 10,000 IU. Concomitant renal failure developed in two of these patients, and one died in hepatic coma. To determine whether alcohol enhances acetaminophen hepatotoxicity, a lethal dose for 50% survival of a test group (LD50) was performed for mice fed 10% alcohol in their water supply for three weeks and for mice receiving a normal diet only. A significant reduction in the LD50 was seen in the alcohol-pretreated mice, and correlations were noted between histological findings in the liver and the LD50 data. These findings suggest that alcohol enhances acetaminophen hepatotoxicity in mice and provides supportive evidence that these three alcoholic patients probably had a similar pathophysiological basis for their liver disease.

Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak ×100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients.

The accumulation of false neurotransmitters such as octopamine and depletion of true neurotransmitters such as dopamine have been purported to play a pathogenetic role in portal systemic encephalopathy (PSE). Therefore, we measured plasma prolactin, a known sensitive indicator of functional dopamine activity in man, in an attempt to evaluate dopaminergic function in 21 patients with alcoholic liver disease and PSE and several control groups. Subjects with PSE had markedly elevated prolactin levels (P less than 0.01) when compared to all control groups. Moreover, patients with PSE were divisible into two groups, 12 having mildly increased prolactin levels and 9 having markedly elevated levels. Although the degree of PSE was similar in both groups, those PSE patients with the higher prolactin values had significantly greater derangement of serum albumin, bilirubin, prothrombin time, and also had a higher mortality (100%). These data: (1) provide evidence consistent with the hypothesis of altered neurotransmitter function in individuals with chronic alcoholic liver disease, particularly those manifesting evidence of PSE; (2) suggest that altered dopamine function in chronic liver disease may have pathophysiologic significance as judged by altered hormone release; (3) demonstrate that a markedly elevated plasma prolactin level in individuals with PSE carries an ominous prognosis; and (4) suggest a possible role for the plasma prolactin in the selection and monitoring of PSE patients who are to be treated with agents aimed at correcting neurotransmitter abnormalities.