RESUMO
CONTEXT: Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. OBJECTIVE: To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. METHODS: In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. RESULTS: The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6-75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14-118.4) and only five (23%) controls (median, < Lower Limit of Quantitation (LLQ); range, < LLQ-43.3 mcg/mL). Significant differences and associations were identified between case status and the following: 1) serum oxalic acid and serum HEAA (both OR = 14.6; 95% C I = 2.8-100.9); 2) serum diglycolic acid and urine diglycolic acid (both OR > 999; exact p < 0.0001); and 3) urinary glycolic acid (OR = 0.057; 95% C I = 0.001-0.55). Two CSF sample results were excluded and two from the same case were averaged, yielding eight samples from eight cases. Diglycolic acid was detected in seven (88%) of case CSF samples (median, 2.03 mcg/mL; range, < LLQ, 7.47). DISCUSSION: Significantly elevated HEAA (serum) and diglycolic acid (serum and urine) concentrations were identified among cases, which is consistent with animal data. Low urinary glycolic acid concentrations in cases may have been due to concurrent AKI. Although serum glycolic concentrations among cases may have initially increased, further metabolism to oxalic acid may have occurred thereby explaining the similar glycolic acid concentrations in cases and controls. The increased serum oxalic acid concentration results in cases versus controls are consistent with this hypothesis. CONCLUSION: Diglycolic acid is associated with human DEG poisoning and may be a biomarker for poisoning. These findings add to animal data suggesting a possible role for traditional antidotal therapies. The detection of HEAA and diglycolic acid in the CSF of cases suggests a possible association with signs and symptoms of DEG-associated neurotoxicity. Further work characterizing the pathophysiology of DEG-associated neurotoxicity and the role of traditional toxic alcohol therapies such as fomepizole and hemodialysis is needed.
Assuntos
Etilenoglicóis/sangue , Etilenoglicóis/líquido cefalorraquidiano , Etilenoglicóis/intoxicação , Etilenoglicóis/urina , Intoxicação/diagnóstico , Acetatos/líquido cefalorraquidiano , Acetatos/intoxicação , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/urina , Estudos de Casos e Controles , Centers for Disease Control and Prevention, U.S. , Feminino , Fomepizol , Cromatografia Gasosa-Espectrometria de Massas , Glicolatos/sangue , Glicolatos/líquido cefalorraquidiano , Glicolatos/intoxicação , Glicolatos/urina , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Modelos Logísticos , Masculino , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Panamá , Intoxicação/tratamento farmacológico , Intoxicação/etiologia , Pirazóis/uso terapêutico , Diálise Renal , Manejo de Espécimes , Estados UnidosRESUMO
The cluster-sampling method can be used to conduct rapid assessment of health and other needs in communities affected by natural disasters. Modelled after WHO's Expanded Programme on Immunization method of estimating immunization coverage, the method has been modified to provide (1) estimates of the population remaining in an area, and (2) estimates of the number of people in the post-disaster area with specific needs. This approach differs from that used previously in other disasters where rapid needs assessments only estimated the proportion of the population with specific needs. We proposed a modified n x k survey design to estimate the remaining population, severity of damage, the proportion and number of people with specific needs, the number of damaged or destroyed and remaining housing units, and the changes in these estimates over a period of time as part of the survey
El método de muestreo por conglomerados puede utilizarse para llevar a cabo la evaluación rápida de las necesidades de salud y de otro tipo en comunidades afectadas por desastres naturales. El método, que se basa en el modelo usado por el Programa Ampliado de Inmunización de la OMS para estimar la cobertura con vacunación, ha sido modificado para que proporcione 1) estimaciones de la población que queda en una zona determinada y 2) estimaciones del número de personas con necesidades específicas en la zona que ha sido afectada por un desastre. Este enfoque difiere del que se ha usado anteriormente a raíz de otros desastres en que las evaluaciones rápidas de las necesidades solo han consistido en estimar la proporción de la población con necesidades específicas. Aquí se propone un diseño de encuesta modificado que se basa en el uso de n k para calcular la población restante, la gravedad del daño, la proporción y el número de personas con necesidades específicas, el número de domicilios dañados o destruidos y los cambios que sufren estas estimaciones en determinado período como parte de la encuesta
Assuntos
Saneamento em Desastres , Amostragem por Conglomerados , Necessidades e Demandas de Serviços de Saúde , Avaliação de Danos , Planejamento em Desastres/organização & administração , Medição de Risco , Coleta de Dados/métodosRESUMO
Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound.