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Biomedical subjects

G Danan

Publications and source records attributed to G Danan.

At least 37 records · Page 2Linked to original sources
PubMed1986

Cross hepatotoxicity between tricyclic antidepressants.

Cross hepatotoxicity between drugs in very uncommon. We report the case of a patient in whom acute hepatitis was induced by a tricyclic antidepressant, amineptine, and recurred early after administration of another tricyclic antidepressant, clomipramine. This observation suggests that the tricyclic ring is involved in the mechanism of the deleterious effect of both drugs to the liver.

Acute Disease↗
PubMed1985

Pirprofen-induced fulminant hepatitis.

We report the cases of 2 female patients aged 69 and 61 yr, suffering from fulminant hepatitis induced by pirprofen, a new nonsteroidal antiinflammatory drug. The duration of pirprofen administration before the onset of hepatitis was long, 7 and 9 mo, respectively. Hepatitis was not preceded or accompanied by hypersensitivity manifestations. The liver lesion consisted of massive, predominantly centrilobular hepatic cell necrosis and microvesicular steatosis. One patient died of liver failure. Although the risk of fulminant hepatitis is very low, we recommend that, in patients taking pirprofen for more than 2 mo and complaining of asthenia, nausea, or vomiting, serum aminotransferase levels should be measured and administration of the drug should be interrupted as soon as an increased level is noted.

Aged↗
PubMed1985

Pefloxacin kinetics in cirrhosis.

Pefloxacin pharmacokinetics were evaluated in 16 patients with histologically proved cirrhosis of the liver and compared with those in 12 healthy subjects. In the patients with cirrhosis, the mean (+/- SD) t1/2, although highly variable, was significantly longer (35.10 +/- 19.00 hours) than in the normal subjects (11.00 +/- 2.64 hours; P less than 0.001). In the patients, the volume of distribution was decreased by 18% (P less than 0.02) and total plasma clearance was markedly decreased (2.66 +/- 1.85 vs. 8.19 +/- 2.80 L/hr X 1.73 m2; P less than 0.001). The t1/2 was longer in patients with ascites or jaundice than in patients without these complications. The urinary excretion of unchanged pefloxacin was higher in the patients than in the subjects, while the excretion of N-desmethyl pefloxacin (a major metabolite of the drug) was lower. It is proposed that the decreased plasma clearance of pefloxacin in patients with cirrhosis is a result of decreased hepatic metabolism of the drug, and that the dosage should probably be modified in these patients.

Adult↗
PubMed1984

Partial hepatectomy in the treatment of Caroli's disease. Report of a case and review of the literature.

We describe a 28-yr-old woman who presented with severe, recurrent cholangitis due to Caroli's disease in association with congenital hepatic fibrosis. Cystic dilatation of the segmental bile ducts was diffuse, but predominated in the right lobe and left medial segment of the liver. Extended right lobectomy was followed by cessation of cholangitis. Partial hepatectomy should be considered for the treatment of Caroli's disease in the patients with severe, recurrent cholangitis in whom cystic dilatation of the intrahepatic bile ducts predominates in a part of the liver.

Adult↗
PubMed1984

Recurrent jaundice caused by recurrent hyperemesis gravidarum.

The existence of jaundice induced by hyperemesis gravidarum is controversial. We report the case of a woman who suffered from three episodes of jaundice during the first trimester of three consecutive pregnancies, a few days after the onset of hyperemesis gravidarum. Jaundice was caused by conjugated hyperbilirubinaemia. Serum alanine aminotransferase activity was increased and scarce necrotic hepatocytes were shown on light and electron microscopic examinations. Cessation of vomiting was rapidly followed by complete recovery. This observation supports the view that severe vomiting can cause jaundice in pregnant women.

Adult↗
PubMed1984

Amitriptyline-induced fulminant hepatitis.

The authors report the case of a patient who received amitriptyline on 2 occasions. On both occasions, she had fever and jaundice. On the second episode, hepatitis was severe with hepatic encephalopathy, ascites, increased prothrombin time, and massive hepatic necrosis. After interruption of the drug administration, the patient made a slow but complete recovery.

Amitriptyline↗
PubMed1984

Mechanism for isaxonine hepatitis. I. Metabolic activation by mouse and human cytochrome P-450.

The metabolism of isaxonine was first investigated in mice. Incubation, under air, of [2-14C] isaxonine (1 mM) with mouse liver microsomes and an NADPH-generating system resulted in the irreversible binding of a [14C] isaxonine metabolite to microsomal proteins; binding required active microsomes, NADPH and oxygen, it was inhibited by 4 mM piperonyl butoxide or by a CO-O2 (80:20) atmosphere. In the presence of various concentrations of isaxonine (0.125-2 mM), binding followed Michaelis-Menten kinetics; the Vmax was increased by both phenobarbital and 3-methylcholanthrene pretreatments. In vivo, 2.5 hr after the administration of [2-14C] isaxonine (4 mmol X kg-1 i.p.), a [14C] isaxonine material was irreversibly bound to mouse liver proteins; this binding was decreased by piperonyl butoxide and increased by phenobarbital or 3-methylcholanthrene pretreatments. Irreversible binding also occurred in the kidney. Unlike their effects in the liver, piperonyl butoxide and phenobarbital did not modify significantly in vitro metabolic activation by kidney microsomes and in vivo covalent binding to kidney proteins; pretreatment with 3-methylcholanthrene increased both in vitro and in vivo binding in the kidney. In a second series of experiments, in vitro metabolic activation was demonstrated with human liver microsomes; as in mice, covalent binding required NADPH and was markedly inhibited by piperonyl butoxide. We conclude that isaxonine is activated by mouse and human cytochromes P-450 into a reactive metabolite. In vivo covalent binding to mouse liver and kidney proteins appears to result mainly from the in situ binding of the metabolite formed in each organ.

Animals↗
PubMed1983

[Iproniazid-induced hepatitis. The diagnostic value of a new antimitochondrial antibody anti-M6].

The authors report the observations of four patients with iproniazid hepatitis. Three of these patients died. An antimitochondrial antibody was found in the 4 patients at a high titer. This antibody differed from the antimitochondrial antibodies which have been described previously (anti-M1, anti-M5). This new antibody was called anti-M6. The evolution of the anti-M6 titer has been studied in the patient who survived. This titer progressively decreased; the antibody was no longer detectable 6 months after the withdrawal of iproniazid. Anti-M6 has not been found in other hepatic diseases. It was not detected in 15 patients receiving iproniazid without hepatitis or in 6 patients receiving isoniazid. Anti-M6 appears as a useful serologic marker for the diagnosis of iproniazid hepatitis.

Adult↗
PubMed1981

Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450.

Erythromycin, 0.3 mM, elicited a small reverse type I binding spectrum with, and was slowly demethylated by, cytochrome P-450 from control rats. No absorption peak at 456 nm could be detected upon incubation of 0.3 mM erythromycin with NADPH and control microsomes. No complex formed in vivo could be detected in microsomes isolated 2 hr after a single dose of erythromycin, 2 mmol.kg-1 p.o. Repeated administration of erythromycin, 2 mmol.kg-1 p.o. daily for 4 days increased hepatic microsomal protein concentration, NADPH-cytochrome c reductase activity, the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity. Microsomes isolated from rats treated with repeated doses of erythromycin exhibited a marked absorption peak at 456 nm. The absorption at 456 nm was further increased upon incubation with erythromycin and NADPH. It disappeared upon addition of 50 muM potassium ferricyanide. Disruption of the complex with potassium ferricyanide markedly increased the CO-binding capacity of dithionite-reduced microsomes. It further increased the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity and increased ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase activities. It is concluded that erythromycin induces its own transformation into a metabolite which forms a inactive 456-nm absorbing complex with the iron (II) of cytochrome P-450.

Animals↗