N-Nitrosodimethylamine (NDMA) is a potent hepatotoxicant in the rat, but the mechanism by which it lethally injures hepatocytes is not known. NDMA is metabolized in the liver to the methanediazonium ion that methylates hepatic DNA. Neither N-nitrosomethylbenzylamine (NMBzA) nor methylnitrosourea (MNU) produces liver tumors, but via metabolism in the case of NMBzA, or via spontaneous decomposition at physiological pH in the case of MNU, both compounds produce the methanediazonium ion and methylate hepatic DNA. Here we have compared quantitatively the ability of NDMA, NMBzA, and MNU to cause lethal injury to hepatocytes in vivo and to produce O6-methylguanine in hepatic DNA. Neither NMBzA nor MNU produced hepatotoxicity in the rat even at doses as high as 667 mumol/kg body wt for NMBzA and 971 mumol/kg body wt for MNU. NMBzA given at the same time as NDMA potentiated the hepatotoxicity of NDMA, but O6-methylguanine levels were only additive. MNU did not potentiate the hepatotoxicity of NDMA, but again, the O6-methylguanine levels were additive when NDMA and MNU were administered together. These results appear to rule out the involvement of DNA methylation in lethal hepatocyte injury by NDMA.

Animals↗

PubMedDate not supplied

The use of exchange transfusions: a potentially useful adjunct in the treatment of fulminant falciparum malaria.

Fulminant falciparum malaria with greater than 500,000/mm3 parasites in the peripheral blood portends a poor prognosis. We recently managed a patient who had greater than 1.2 million/mm3 parasitized erythrocytes in her peripheral blood, following initially inadequate antimalarial therapy, with exchange transfusion in addition to conventional chemotherapy. This patient recovered from her disease despite severe cerebral involvement and acute failure. We feel that exchange transfusion was a useful adjunct and should be considered in patients with life threatening falciparum malaria when conventional measures fail to control the disease.

Adult↗