RESUMO
STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS: One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis. RESULTS: Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used. CONCLUSION: In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.
Assuntos
Amanitinas/intoxicação , Antídotos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Intoxicação Alimentar por Cogumelos/tratamento farmacológico , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Alanina Transaminase/sangue , Animais , Antídotos/administração & dosagem , Aspartato Aminotransferases/sangue , Cimetidina/administração & dosagem , Cimetidina/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos , Penicilina G/administração & dosagem , Penicilina G/farmacologia , Distribuição Aleatória , Silibina , Silimarina/administração & dosagem , Silimarina/farmacologia , Ácido Tióctico/administração & dosagem , Ácido Tióctico/farmacologiaRESUMO
Cervical lymphadenitis and fever are common in patients presenting to the Emergency Department (ED). Kikuchi's disease is a rare, self-limited cause of fever and cervical lymphadenitis often misdiagnosed as lymphoma or lupus and inappropriately treated, potentially causing numerous ED visits for unrelieved symptoms. The case described is that of a 29-year-old with persistent fever and cervical lymphadenitis who presented to the ED with a suspected allergic reaction to an antibiotic. The diagnosis of Kikuchi's disease was made in association with nasopharyngeal carcinoma and partial hydatidiform mole. The case highlights the clinical features, diagnosis, and treatment of Kikuchi's disease.