ABSTRACT
No disponible
Subject(s)
Humans , History, 20th Century , History, 21st Century , Anti-Bacterial Agents/therapeutic use , Chloramphenicol/therapeutic use , Eye Infections/drug therapy , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/history , Chloramphenicol/adverse effects , Chloramphenicol/historySubject(s)
Anti-Bacterial Agents/therapeutic use , Chloramphenicol/therapeutic use , Eye Infections/drug therapy , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/history , Chloramphenicol/adverse effects , Chloramphenicol/history , History, 20th Century , History, 21st Century , HumansSubject(s)
Biomedical Research/history , Death , Genetic Therapy/history , Healthy Volunteers , Physicians/history , Research Personnel/history , Research Subjects , Withholding Treatment/history , Anti-Bacterial Agents/history , Anti-Bacterial Agents/therapeutic use , Biomedical Research/ethics , Biomedical Research/legislation & jurisprudence , Chloramphenicol/history , Chloramphenicol/therapeutic use , Genetic Therapy/ethics , HeLa Cells , Healthy Volunteers/history , History, 20th Century , Humans , Legislation, Medical/trends , Physicians/ethics , Research Personnel/ethics , Research Subjects/history , Typhoid Fever/drug therapy , Typhoid Fever/history , Typhoid Fever/mortality , United States , Withholding Treatment/ethicsSubject(s)
Anti-Bacterial Agents/history , Chloramphenicol/history , Typhoid Fever/history , Anti-Bacterial Agents/therapeutic use , Baltimore , Chloramphenicol/therapeutic use , Controlled Clinical Trials as Topic/history , History, 20th Century , Humans , International Cooperation/history , Malaysia , Typhoid Fever/drug therapyABSTRACT
Significant progress has been made in recent years in the understanding of the pathogenesis of the two types of hematologic toxicity from chloramphenicol. The common, dose-dependent, reversible bone marrow suppression from chloramphenicol is a consequence of mitochondrial injury. The greater erythroid susceptibility to chloramphenicol appears to be a function of the endogenous mitochondrial amino acid pools. The pathogenesis of aplastic anemia from chloramphenicol treatment remains uncertain. A large body of indirect evidence favors a complex mechanism involving metabolic transformation of the p-NO2 group of chloramphenicol by the predisposed subject, leading to the production of a toxic intermediate causing stem cell damage. A concept is presented wherein metabolites of chloramphenicol generated by intestinal bacteria undergo further metabolic transformation in the bone marrow with in situ production of toxic intermediate. This concept of the marrow being both the metabolic site for the offending agent as well as the target for its toxic metabolites will likely apply to other potential myelotoxins.
