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Objective In September 2006, a Panamanian physician reported an unusual number of patients with unexplained acute renal failure frequently accompanied by severe neurological dysfunction. Twelve (57%) of 21 patients had died of the illness. This paper describes the investigation into the cause of the illness and the source of the outbreak. Methods Case-control and laboratory investigations were implemented. Case patients (with acute renal failure of unknown etiology and serum creatinine [greater than or equal to] 2 mg/dl) were individually matched to hospitalized controls for age (+ or -] 5 years), sex and admission date ([less than or equal to] 2 days before the case patient). Questionnaire and biological data were collected. The main outcome measure was the odds of ingesting prescription cough syrup in cases and controls. Findings Forty-two case patients and 140 control patients participated. The median age of cases was 68 years (range: 25-91 years); 64% were male. After controlling for pre-existing hypertension and renal disease and the use of angiotensin-converting enzyme inhibitors, a significant association was found between ingestion of prescription cough syrup and illness onset (adjusted odds ratio: 31.0, 95% confidence interval: 6.93-138). Laboratory analyses confirmed the presence of diethylene glycol (DEG) in biological samples from case patients, 8% DEG contamination in cough syrup samples and 22% contamination in the glycerin used to prepare the cough syrup. Conclusion The source of the outbreak was DEG-contaminated cough syrup. This investigation led to the recall of approximately 60 000 bottles of contaminated cough syrup, widespread screening of potentially exposed consumers and treatment of over 100 affected patients. Objectif En septembre 2006, un medecin panameen a signale un nombre inhabituel d'insuffisances renales aigues inexpliquees, s'accompagnant frequemment d'un dysfonctionnement neurologique severe, Douze (57 %) des 21 malades sont morts de cette insuffisance. Le present article decrit l'enquete reatisee sur les causes de la maladie et l'origine de la flambee epidemique. Methodes Une etude cas-temoin et des investigations en laboratoire ont ete menees. Les cas (personnes presentant une insuffisance renale aigue d'etiologie inconnue et un taux de creatinine serique [superieur ou egal a] 2 mg/dl) ont ete apparies individuellement a des temoins hospitalises en fonction de l'age ([+ o-] 5 ans), du sexe et de la date d'admission (2 jours au plus avant la declaration du cas ou plus tard). Un questionnaire et des donnees biologiques ont ete recueillis. La principale mesure de resultat etait l'odds ratio de la prise de sirop antitussif sur prescription par les cas et les temoins. Resultats Quarante-deux cas et 140 temoins ont ete inclus dans l'etude. L'age median des cas etait de 68 ans (plage de variation : 25-91 ans) et 64% d'entre eux etaient des hommes. Apres ajustement pour une hypertension ou une pathologie renale preexistante et pour l'utilisation d'inhibiteurs de l'enzyme de conversion de l'angiotensine, une association importante a ete relevee entre la prise de sirop antitussif soumis a prescription et l'apparition de la maladie (odds ratio ajuste : 31,0, intervalle de confiance a 95% : 6,93-138). Les analyses de laboratoire ont confirme la presence de diethylene glycol (DEG) dans les echantillons biologiques provenant des cas, un taux de contamination par le DEG de 8 % des echantillons de sirop pour la toux et un taux de contamination de 22 % de la glycerine ayant servi a preparer ce sirop. Conclusion L'origine de la flambee etait un sirop antitussif contamine par du DEG. Les investigations ont conduit au rappel d'environ 60 000 flacons de sirop contamine, a un depistage a grande echelle des consommateurs potentiellement exposes et au traitement de plus de 100 patients touches. Objetivo En septiembre de 2006, un medico panameno notifico un numero inhabitual de pacientes aquejados de insuficiencia renal aguda idiopatica, asociada con frecuencia a disfuncion neurologica grave. Doce (57%) de 21 pacientes habian muerto a causa de la enfermedad. Se describe aqui la investigacion realizada para determinar la causa de la enfermedad y la fuente dei brote. Metodos Se Ilevaron a cabo estudios de casos y controles e investigaciones de laboratorio. Los pacientes objeto de estudio (con insuficiencia renal aguda de origen desconocido y creatinina serica [mayor que o iqual a] 2 mg/dl) fueron apareados individualmente con pacientes control hospitalizados considerando la edad ([+ 0-] 5 anos), el sexo y la fecha de ingreso ([menor que o igual a] 2 dias antes o despues del ingreso del paciente estudiado). Se recopilaron dates de cuestionarios y dates biologicos. El criterio principal de valoracion fueron las posibilidades de cases y controles de haber tornado jarabe contra la tos de venta con receta. Resultados Participaron en el estudio 42 cases y 140 controles. La mediana de la edad de los cases fue de 68 anos (intervalo: 25-91 anos); el 64% eran varones. Tras determinar si los pacientes presentaban una historia previa de hipertension y nefropatia y de use de inhibidores de la enzima conversora de la angiotensina, se detecto una relaci6n significativa entre la ingestion de jarabe antitusigeno y la aparicion de la enfermedad (razon de posibilidades (OR) ajustada: 31,0, intervalo de confianza del 95%: 6,93-138). Los analisis de laboratorio confirmaron la presencia de dietilenglicol (DEG) en las muestras biologicas de los pacientes estudiados, con una contaminacion per DEG del 8% en las muestras de jarabe y del 22% en la glicerina utilizada para preparar dicho jarabe. Conclusion La fuente del brote fue el jarabe antitusigeno contaminado per DEG. Esta investigacion Ilevo a retirar aproximadamente 60 000 frascos del jarabe contaminado, realizar un amplio cribado de los consumidores potencialmente expuestos, y tratar a mas de cien pacientes afectados., Introduction Diethylene glycol (DEG) is a colourless and odourless liquid and a human toxicant. It is commonly used in industry and can be found in commercial products such as resins, [...]

BACKGROUND. Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide [...]

Methyl eugenol is a naturally occurring material found in a variety of food sources, including spices, oils, and nutritionally important foods such as bananas and oranges. Given its natural occurrence, [...]

BACKGROUND: We previously reported widespread insecticide exposure during pregnancy among inner-city women from New York City. Here we report on a pilot intervention using integrated pest management (IPM) to reduce [...]

OBJECTIVE. We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers' children in California. METHODS. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p'-DDT, o,p'-DDT, and p,p'-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS. We found a ~2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p'-DDT levels at 6 and 12 months (but not 24 months) and p,p'-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p'-DDT and o,p'-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment. www.pediatrics.org/cgi/doi/10.1542/ peds.2005-3117 doi:10.1542/peds.2005-3117 Key Words dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, organochlorine, pesticides, neurodevelopment, Bayley Scales of Infant Development Abbreviations CHAMACOS--Center for the Health Assessment of Mothers and Children of Salinas DAP--dialkyl phosphates HCB--hexachlorobenzene HOME--Home Observation for Measurement of the Environment LOD--limit of detection MDI--Mental Developmental Index DDT--dichlorodiphenyltrichloroethane PDI--Psychomotor Developmental Index DDE--dichlorodiphenyldichloroethylene PCB--polychlorinated biphenyl [beta]-HCCH-[beta]-hexachlorocyclohexane PPVT--Peabody Picture Vocabulary Test CI--confidence interval Accepted for publication Feb 15, 2006, IN 2001, >90 countries signed the Stockholm Convention on Persistent Organic Pollutants, committing to eliminate the use of 12 persistent organic pollutants of greatest concern to the ecology and health [...]

The ability to estimate low-dose human exposure to commonly used pesticides often is requested in epidemiologic studies. Therefore, fast and robust methods are necessary that can measure many analytes in the same sample. We have developed a method for high-throughput analysis of 19 markers of commonly used pesticides in human urine. The analytes were seven specific metabolites of organophosphorus pesticides, five metabolites of synthetic pyrethroids, six herbicides or their metabolites, and one insect repellant. Human urine (2 mL) was spiked with stable isotopically labeled analogues of the analytes, enzymatically hydrolyzed, extracted using solid-phase extraction, concentrated, and analyzed using high-performance liquid chromatography-tandem mass spectrometry. The sample was divided into two portions and analyzed on two different mass spectrometers, one using atmospheric pressure chemical ionization (APCI) and the other using turbo ion spray atmospheric pressure ionization (TIS). All analytes except the pyrethroid metabolites were analyzed using APCI. The detection limits for all analytes ranged from 0.1 to 1.5 ng/mL of urine, with the majority (17) below 0.5 ng/mL. The analytical precision for the different analytes, estimated as both the within-day and between-day variation, was 3-14 and 4-19%, respectively. The extraction recoveries of the analytes ranged from 68 to 114%. The throughput, including calibration standards and quality control samples, is ~50 samples a day. However, the analysis time with the TIS application is much shorter, and if only pyrethroid metabolite data are of interest, the throughput can be increased to 100-150 samples/day.

The Centers for Disease Control and Prevention (CDC) is involved in many epidemiological studies regarding the measurement of chlorinated pesticides and polychlorinated biphenyls in specimens obtained from humans. In addition to these commonly determined analytes, there is a need to include additional persistent organic pollutants (POPs) in our analyses, which further stresses the analyses because sample volumes remain small. Thus, a single method of analysis for all POPs in human serum is needed. CDC has recently developed a semiautomated and comprehensive solid-phase extraction method for POPs. The method is comprehensive since it was optimized for the extraction of many different POP compound classes. We then developed a purification and fractionation scheme that allows (a) separation of different compound classes by particular functionalities and (b) purification of those fractions to remove coextracted interferences. This paper describes the first step in the semiautomated comprehensive extraction and multiple fractionation method developed by CDC for monitoring POPs. In this paper, we validate the analysis of the persistent chlorinated pesticides, a compound class difficult to examine because of their structural diversity, in human plasma. The method was validated against an existing CDC method by using a spiked quality-control serum pool. The concentrations determined for all analytes using both methods were within 2%-14% relative standard deviations. A multilevel (i.e., 3-4 point) matrix spike showed good linearity for the analytes tested ([r.sup.2] = 0.978-0.999). The method was then applied to 40-year-old archived plasma samples for the quantitative analysis of selected chlorinated pesticides. Mean recoveries of the [sup.13]C-labeled internal quantification standards ranged from 64% to 123% for the 11 monitored pesticides. The overall method proved to be robust by handling old coagulated plasma samples. It allowed faster throughput of samples than our previous methods and provided cleaner samples with less frequent interferences or background as analyzed by high-resolution mass spectrometry. The method represents a preliminary step in establishing an automated, comprehensive multiresidue analysis method for POPs in human serum.