Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetaminophen-induced (750 mg per kg p.o.) hepatotoxicity in mice is characterized by hepatomegaly and massive centrilobular congestion which precede the appearance of necrosis. The vascular changes are correlated with the morphologic features using liver hemoglobin content to quantitate erythrocyte sequestration, and hematocrit measurements and 125I-albumin injections to determine plasma and blood volume. The initial increase in liver size was a result of plasma accumulation due to endocytic vacuolation of hepatocytes and Disse space enlargement in centrilobular regions. Further increases in liver size after 3 hr were a consequence of erythrocyte and additional plasma sequestration within the damaged liver. These events occurred without any increase in intrahepatic or portal venous pressure. Hepatic hemoglobin and plasma levels increased 10- and 5-fold, respectively, by 4.5 to 6 hr after administration of acetaminophen. There are two major consequences of acetaminophen-induced hepatotoxic congestion. First, blood and plasma volumes fell significantly, and we suggest that hypovolemic shock contributes to early mortality after acetaminophen. Second, impaired circulation within the congested liver, as manifested by reduced 125I-albumin entry into the liver when 125I-albumin was injected after congestion had developed, probably aggravates the initial injury. Early lesions were always evenly distributed around central veins. However, the pattern of damage at 24 hr could be variable. Occasional large confluent areas of necrosis were always congested, which is consistent with the concept that secondary ischemic damage can develop. Congestion and hypovolemia are reversible and can be largely prevented by administration of the protective compound N-acetylcysteine (1,200 mg per kg p.o.) 3 hr after acetaminophen.
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PMID:Acetaminophen-induced hepatotoxic congestion in mice. 397 55

Hepatic sinusoidal obstruction syndrome is commonly described in pediatric oncology as a complication of chemotherapy. It has also been occasionally reported in adult cancer patients. Treatment is largely supportive with fluid restriction. A 16-month-old girl with stage II Wilms tumor receiving post-nephrectomy chemotherapy with dactinomycin and vincristine developed hepatic sinusoidal obstruction syndrome with painful hepatomegaly, ascites with significant weight gain, grossly deranged liver function, severe thrombocytopenia, and reversal of blood flow in the portal vein on Doppler sonography. Treatment with N-acetylcysteine was followed by complete resolution of clinical signs and amelioration of laboratory abnormalities within 72 hours of treatment. N-acetylcysteine is a safe and probably an effective treatment for dactinomycin-induced hepatic sinusoidal obstructive syndrome.
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PMID:Dactinomycin-induced Hepatic Sinusoidal Obstruction Syndrome Responding to Treatment with N-acetylcysteine. 2204 37