Necrosis hepatic

Priest RJ, Horn RC. 1965. Trichloroethylene intoxication A case of acute hepatic necrosis possibly due to this agent. Arch Environ Health 11 361-365. 

Mitchell, J.R., follow, D.J., Potter, W.Z., Davis, D.C., Gillette, J.R. and Brodie, B.B. (1973a). Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J. Pharmacol. Exp. Ther. 187, 185-194. 

Speisky, H., Bunou, D., Orrego, H. and Israel, Y. (1985). Lack of changes in diene conjugate levels following ethanol-induced glutathione depletion or hepatic necrosis. Res. Commun. Chem. Pathol. Pharmacol. 48, 77-90. 

Acute hepatic necrosis (e.g., chronic or acute hepatitis B or C)... 

Rash including Stevens-Johnson syndrome symptomatic hepatitis, including fatal hepatic necrosis... 

Beagle dog inhalation "CeCl, AMAD t.5-2,4 ion a, 1.6-2.1 13-16 mos 70 life span (in progress) death, bone marrow aplasia and pancytopenia, radiation pneumonitis, pulmonary fibrosis, hepatic necrosis 11/48 Yes pulmonary adenoma, bronchtogenic adenocarcinoma 3/48 Yes he man- Yes giocarcinoma osteosarcoma, 6/48 leukemia 3/34 (primary) Benjamin et al. (1972b 1976c) Merickel et al. (1978)... 

The answer is d. (Hardman, pp 308-313.) Halothane is a substituted alkane general anesthetic. It undergoes significant metabolism in humans with about 20% of the absorbed dose recovered as metabolites. Halothane can cause postoperative jaundice and hepatic necrosis with repeated administration in rare instances. 

No data were found on the effects of silver compounds on avian or mammalian wildlife. All controlled studies with silver were with domestic poultry, livestock, or small laboratory mammals. Signs of chronic silver ion intoxication in tested birds and mammals included cardiac enlargement, vascular hypertension, hepatic necrosis, anemia, lowered immunological activity, altered membrane permeability, kidney pathology, enzyme inhibition, growth retardation, and a shortened life span (Smith and Carson 1977 Freeman 1979 Fowler and Nordberg 1986 USPHS 1990). 

Hepatic necrosis and lameness in dogs, horses, and breeding bulls... 

An MRL of 1 mg/kg/day has been calculated for acute oral exposure to hexachloroethane based on a NOAEL of 100 mg/kg/day from a study in male rabbits (Weeks et al. 1979). Hepatic necrosis and degeneration were observed in the treated animals at doses of 320 and 1,000 mg/kg/day. 

In the course of studies on other pathological amino acidurias, the accompanying peptiduria has also been observed by many authors. Rapp de Eston et al. (R2) observed a marked increase in the excretion of both free amino acids and peptides in patients with diffuse hepatic necrosis. Using a simplified chromatographic method adapted to clinical purposes and suitable for analysis of amino acids excreted with urine, Skarzynski et al. (S5) demonstrated a raised level of a certain peptide which is always present in normal urine in smaller quantities, as well as the appearance of some new peptides in cases of jaundice and liver cirrhosis. Some abnormal peptide spots were also detected on the chromatograms in cases of progressive muscular dystrophy (K4) and in patients irradiated with X-rays (S2). 

R2. Rapp de Eston, V., Wajchenberg, B. L., Weston, T., and Pagano, C., Urinary excretion of amino acids in diffuse hepatic necrosis. Gastroenterology 29, 71-81 (1955). 

A systematic series of studies on the ECT of pig liver have appeared from the Australian group of Maddern et al. Electrolysis was investigated for generating areas of hepatic necrosis in the pig liver.88 The lesions healed with time and were associated with minimum morbidity. Further work on 21 pigs showed that during ECT of the liver tissue the electrolytic dose (in coulombs cm"3) correlated with the volume of liver necrosis.89 This group also established that in addition to the coulombic dose, pH could be used as a realtime monitor to predict more accurately the extent of necrosis. 

Recently, the role of hydrazine in the mechanism of isoniazid hepatotox-icity was confirmed by Sarich et al. [181]. Using a model of isoniazid-in-duced hepatotoxicity in rabbits, they found that hydrazine plasma concentrations correlated significantly with plasma argininosuccinic acid lyase, a sensitive marker of hepatic necrosis. In contrast, no correlation was found between plasma levels of isoniazid or acetylisoniazid and the markers of induced hepatic necrosis. 

Ilett KF, Reid WD, Sipes IG, et al. 1973. Chloroform toxicity in mice Correlation of renal and hepatic necrosis with covalent binding of metabolites to tissue macromolecules. Exp Mol Pathol 19 215-229. 

Paracetamol overdose is most likely to cause hepatic necrosis and to a lesser extent renal necrosis. Hepatic necrosis is maximal within 3-4 hours of ingestion and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acetylcysteine tends to protect the liver if given within 10-12 hours of paracetamol poisoning. The maximum adult dose of paracetamol is 4 g in 24 hours. 

The intermediate metabolites formed during the biotransformation in the liver are believed to be responsible for the hepatoxicity that results in overdosage. Nausea and vomiting are early features of poisoning. With time, hepatic necrosis develops and is often associated with the onset of right subcostal pain and tenderness. 

Only one report of human death attributed to 1,4-dichlorobenzene exposure has been located in the literature. A 60-year-old man and his wife died within months of each other due to acute yellow atrophy of the liver (also known as massive hepatic necrosis or fulminant hepatitis) (Cotter 1953). Their home had been "saturated" with 1,4-dichlorobenzene mothball vapor for a period of about 3-4 months, but no air measurements were available. Clinical symptoms included severe headache, diarrhea, numbness, clumsiness, slurred speech, weight loss (50 pounds in 3 months in the case of the husband), and jaundice. The wife died within a year of the initial exposure however, it was not clear if 1,4-dichlorobenzene was the primary cause of death. This case study did not address whether these individuals consumed excessive amounts of alcohol or had previous medical problems, such as a chronic liver infection. 

Epoxide metabolites can be generated from a variety of aromatic systems. Anticonvulsants are a class of drug whose side-effects, such as hepatic necrosis and aplastic anaemia, are thought to be mediated by chemically reactive epoxide metabolites formed by cytochrome P450 oxidation. For instance phenytoin (Figure 8.6) toxicity is correlated with oxidation and the inhibition of epoxide hydrolase [8]. 

Carbamazepine exerts its anticonvulsant activity through its own action on voltage sensitive sodium channels and those of its relatively stable 10-11-epoxide. The compound shows a number of potential toxicities including skin rash, hepatic necrosis and teratogenicity. It is possible the 10-11-epoxide is the causative agent, but struc-... 

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