Near-fatal poisoning after ricin injection.

OBJECTIVE: To report a near-fatal poisoning after intentional injection of ricin from a castor bean (Ricinus communis) extract. CASE REPORT: A 21 year-old man self-injected ∼3 mL of a castor bean extract intramuscularly and subcutaneously in the left antecubital fossa. Upon admission to our ED (1 h post-exposure; day 1, D1) he was awake and alert, but complained of mild local pain and showed slight local edema and erythema. He evolved to refractory shock (∼24 h post-exposure) that required the administration of a large volume of fluids and high doses of norepinephrine and vasopressin, mainly from D2 to D4. During this period, he developed clinical and laboratory features compatible with systemic inflammatory response syndrome, multiple organ dysfunction, capillary leak syndrome, rhabdomyolysis, necrotizing fasciitis and possible compartment syndrome. The patient underwent forearm fasciotomy on D4 and there was progressive improvement of the hemodynamic status from D7 onwards. Wound management involved several debridements, broad-spectrum antibiotics and two skin grafts. Major laboratory findings within 12 days post-exposure revealed hypoalbuminemia, proteinuria, thrombocytopenia, leukocytosis and increases in cytokines (IL-6, IL-10 and TNF-α), troponin and creatine kinase. Ricin A-chain (ELISA) was detected in serum up to D3 (peak at 24 h post-exposure), with ∼79% being excreted in the urine within 64 h post-exposure. Ricinine was detected in serum and urine by LC-MS up to D5. A ricin A-chain concentration of 246 µg/mL was found in the seed extract, corresponding to the injection of ∼738 µg of ricin A-chain (∼10.5 µg/kg). The patient was discharged on D71, with limited range of motion and function of the left forearm and hand. CONCLUSION: Ricin injection resulted in a near-fatal poisoning that evolved with septic shock-like syndrome, multiple organ dysfunction and necrotizing fasciitis, all of which were successfully treated with supportive care.

Consecutive envenomation of two men bitten by the same coral snake (Micrurus corallinus).

Objective: To report two patients who developed systemic neurotoxicity after consecutive bites by the same coral snake.Case report: Two previously healthy men (32-year-old and 34-year-old) found a coral snake in a woodpile while collecting wood for a barbecue. During the barbecue, both men became drunk and "played" with the snake, believing that they were handling a false coral snake, and were bitten within a few minutes of each other. Both patients were admitted to a referral tertiary care hospital (175 km from where the bites occurred) 16 hours and 19 hours postbite; both showed similar features of envenomation: palpebral ptosis, muscle weakness, dysphagia, and generalized myalgia. No fang marks or local pain were detected in either case. The patients were successfully treated with Brazilian coral snake antivenom (Fab´2) and discharged one-day postadmission, with improvement of myasthenia, but still showing palpebral ptosis. The offending snake was identified as a 42-cm-long Micrurus corallinus. During follow-up, both patients reported a transitory loss of taste that lasted approximately 3-4 weeks postbite.Conclusion: Consecutive bites by the same coral snake may cause systemic neurotoxicity (acute myasthenia) in more than one person, as well as transitory loss of taste, an underreported complication of snakebites.

Fatal ischemic stroke following Tityus serrulatus scorpion sting in a patient with essential thrombocythemia.

CONTEXT: Stroke following scorpion stings is rare. We report a fatal envenomation involving multiple, extensive brain infarcts in a patient with a previous diagnosis of essential thrombocythemia (ET) who was stung by Tityus serrulatus (T. serrulatus). CASE DETAILS: A 44-year-old woman with a diagnosis of low-risk ET (platelets <1,000,000/mm3, age <60 years and no history of thrombosis; positive JAK2V617F mutation) was admitted to a local ED 1 h after being stung by T. serrulatus on the left foot. She developed signs of severe envenomation, including several episodes of profuse vomiting, pallor and confusion soon after the sting, followed by shock (BP: 90/60 to 60/40 mmHg) and was treated with scorpion antivenom, vasopressors and mechanical ventilation. A brain computed tomography (CT) scan (54-h poststing) revealed diffuse bilateral cerebellar hypodensity, with partial involvement of both occipital lobes and thalamus, obstructive hydrocephaly with signs of cerebrospinal fluid extravasation, and ascending transtentorial herniation, suggestive of bilateral ischemia involving the posterior cerebral circulation. External ventricular drainage resulted in no improvement and brain death was confirmed on day 10. DISCUSSION: Several mechanisms have been proposed to explain stroke following scorpion stings, such as sympathetic stimulation, myocardial dysfunction, hypotension/shock, arrhythmias and coagulopathy. Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age (≥60 years) and previous vascular events. Severe scorpion envenomation resulting in myocardial dysfunction and systemic inflammatory response syndrome may increase the overall risk of arterial thrombosis in this patient.

Clinical consequences of Tityus bahiensis and Tityus serrulatus scorpion stings in the region of Campinas, southeastern Brazil.

Scorpion stings account for most envenomations by venomous animals in Brazil. A retrospective study (1994-2011) of the clinical consequences of Tityus scorpion stings in 1327 patients treated at a university hospital in Campinas, southeastern Brazil, is reported. The clinical classification, based on outcome, was: dry sting (no envenoming), class I (only local manifestations), class II (systemic manifestations), class III (life-threatening manifestations, such as shock and/or cardiac failure requiring inotropic/vasopressor agents, and/or respiratory failure), and fatal. The median patient age was 27 years (interquartile interval = 15-42 years). Scorpions were brought for identification in 47.2% of cases (Tityus bahiensis 27.7%; Tityus serrulatus 19.5%). Sting severity was classified and each accounted for the following percentage of cases: dry stings - 3.4%, class I - 79.6%, class II - 15.1%, class III - 1.8% and fatal - 0.1%. Pain was the primary local manifestation (95.5%). Systemic manifestations such as vomiting, agitation, sweating, dyspnea, bradycardia, tachycardia, tachypnea, somnolence/lethargy, cutaneous paleness, hypothermia and hypotension were detected in class II or class III + fatal groups, but were significantly more frequent in the latter group. Class III and fatal cases occurred only in children <15 years old, with scorpions being identified in 13/25 cases (T. serrulatus, n = 12; T. bahiensis, n = 1). Laboratory blood abnormalities (hyperglycemia, hypokalemia, leukocytosis, elevations in serum total CK, CK-MB and troponin T, bicarbonate consumption and an increase in base deficit and blood lactate), electrocardiographic changes (ST segment) and echocardiographic alterations (ventricular ejected fraction <54%) were frequently detected in class III patients. Seventeen patients developed pulmonary edema, 16 had cardiac failure and seven had cardiogenic shock. These results indicate that most scorpion stings involved only local manifestations, mainly pain; the greatest severity was associated with stings by T. serrulatus and in children <15 years old.

Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades / Antidotes and medicines used to treat poisoning in Brazil: needs, availability and opportunities / Antídotos y medicamentos utilizados para tratar intoxicaciones en Brasil: necesidades, disponibilidad y oportunidades

Antídotos e determinados medicamentos são essenciais ao tratamento de algumas intoxicações e não podem sofrer falhas no abastecimento, sob o risco de prejudicar a saúde e a segurança da população. O objetivo deste trabalho foi avaliar a disponibilidade de antídotos e medicamentos recomendados para o tratamento de intoxicações no Brasil. A partir de consensos internacionais, foram selecionados 41 antídotos para análise, todos sem patente em vigência. Desses, 27 são registrados, porém 11 estão disponíveis em formas inadequadas ao tratamento de intoxicações, restando 16 medicamentos comercialmente disponíveis. Somente um terço dos medicamentos necessários para o tratamento de intoxicações está incluído na relação de medicamentos essenciais do país. Em adição, é apresentada proposta de suprimento das demandas a um dos antídotos, anticorpo antidigoxina, considerando a capacidade de produção nacional de imunobiológicos. Os resultados demonstram limitação da assistência adequada aos pacientes intoxicados no país e reforçam a necessidade urgente de políticas públicas na área.

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the population's health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the country's list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazil's domestic capacity for manufacturing immunobiologicals. The study's results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.

Los antídotos y determinados medicamentos son esenciales para el tratamiento de algunas intoxicaciones, y su disponibilidad no puede fallar, o la salud y la seguridad de la población se ponen en peligro. Este estudio tuvo como objetivo evaluar la disponibilidad de antídotos y fármacos recomendados para el tratamiento por intoxicaciones en Brasil. Se seleccionaron para el análisis 41 antídotos de reconocido consenso internacional, todos ellos sin patentes en vigor. Veintisiete estaban registrados en Brasil, pero 11 se venden en preparados farmacéuticos, no apropiados para el tratamiento de intoxicaciones, lo que da como resultado 16 medicamentos disponibles en el mercado. Sólo se incluyen en la lista brasileña de medicamentos esenciales un tercio de los medicamentos necesarios para tratar intoxicaciones. Además, se presenta una propuesta para suplir uno de los antídotos, anticuerpo antidigoxina, considerando la capacidad de producción nacional. Los resultados muestran limitaciones en una atención adecuada a los pacientes intoxicados en Brasil y refuerzan la necesidad urgente de fortalecer las políticas públicas en este ámbito.

[Antidotes and medicines used to treat poisoning in Brazil: needs, availability and opportunities]. / Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades.

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the population's health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the country's list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazil's domestic capacity for manufacturing immunobiologicals. The study's results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.

Diagnóstico e tratamento da intoxicação por chumbo em crianças e adultos / Diagnosis and treatment of lead poisoning in children and adults

O diagnóstico clínico da intoxicação por chumbo deve levar em conta os órgãos-alvo que determinam os sinais e sintomas mais característicos da intoxicação: cérebro, sistema hematopoiético, rins, e sistema nervoso periférico. O órgão alvo crítico é o cérebro, promovendo sinais e sintomas de encefalopatia mais ou menos acentuada, tais como, cefaléia, perda de memória, perda da concentração e atenção em tarefas corriqueiras, alterações de humor, com irritabilidade, depressão, insônia, ou sonolência, estupor, convulsões e coma, dependendo da dose e duração da exposição. O diagnóstico é confirmado pela dosagem de chumbo no sangue (plumbemia) ou na urina (plumbúria), ou de algum dos parâmetrosde efeito do chumbo na cadeia de formação da hemoglobina, tais como o ácido delta minolevulínico no sangue ou na urina e protoporfirina eritrocitária no sangue. O tratamento da intoxicação é feito com quelantes. Por questão de custos e disponibilidade comercial, a experiência acumulada no Brasil restringe-se ao uso do dimercaprol (BAL), do versenato de cálcio (EDTACaNa2) e da D-penicilamina.

Diagnosis of lead intoxication must be based basically on signs and symptoms produced by the main affected target organs: brain, hemopoietic system, kidneys, and periphery nervous system. The critical organ is the brain, promoting signs and symptoms of encephalopathy more or less pronounced according to the dose and duration of exposure. Such a symptoms are: headache, memory loss, concentration and attention problems, humor changes, irritability, depression, insomnia, somnolence, stupor, convulsions and coma. Diagnosis can be confirmed by blood and urine lead measurement, or by dosage of any parameter of lead effect on hemoglobin formation, like delta aminulevulinic acid in blood or urine and blood erythrocyte protoporphirin. Treatment is performed using chelating agents. Considering costs and commercial availability Brazilian experience regarding chelating agents for lead intoxications is limited to the use of dimecaprol (BAL), calcium versenate (EDTACaNa2) and D-penicilamine.

Fontes de exposição humana ao chumbo no Brasil / Lead sources of human exposure in Brazil

Como resultado do crescimento da contaminação ambiental, houve um aumento do interesse relacionado ao acúmulo de metais pesados no corpo humano e seus efeitos danosos. Alguns desses metais, tal como o como chumbo, são elementos não essenciais e exercem efeitos tóxicos no sistema biológico. Apesar das medidas de controle estabelecidas por lei, intoxicações agudas e crônicas por chumbo ainda acontecem no Brasil. Algumas fontes de exposição a este metal são bem conhecidas, como por exemplo, atividades industriais como mineração, além de fábricas de reciclagem de baterias. No entanto, outras fontes, apesar de comuns, são completamente desconhecidas da população. Este artigo visa apresentar uma revisão da literatura passada e atual sobre as diversas fontes de exposição humana ao chumbo no Brasil.

As result of increased environmental contamination, the interest on the accumulation of heavy metals in the human body and its harmful effects has increased. Some metals, such as lead, are non-essential elements and exert toxic effects on biological system. Despite the control measures established by law, acute and chronic intoxication by lead still happen in Brazil. Some sources of lead exposure are wellknown, such as industrial activities like mining and factories for batteries recycling. However, other sources, although common, are completely unknown by population. This article aims to present a review of past and current literature on the various lead sources of human exposure in Brazil.

Metabolismo e toxicidade do chumbo na criança e no adulto / Metabolism and toxicity of lead in children and adults

O chumbo não participa de nenhum passo ou função metabólica essencial ao ser humano. Ao mesmo tempo é o metal não ferroso mais manipulado industrialmente pelo homem desde a antiguidade, o que tem levado à uma contaminação extensa do meio ambiente desde então, proporcionando ainda hoje um aporte regular excessivo desse metal através da ingestão e inalação. Nesta revisão são discutidos aspectos de cinética e dinâmica do chumbo na forma inorgânica, por ser a forma mais comum de apresentação ocupacional e no meio ambiente. Por ser um elemento metálico o chumbo não sofre biotransformação enzimática. O seu “metabolismo” restringe-se a um cinética de distribuição e excreção bastante complexa que, por sua vez, depende da forma química ingerida ou inalada, que definirá seu potencial de oxi-redução e ionização, ligação a proteínas, e passagem por membranas e barreiras, além do acúmulo tecidual e excreção renal. Adultos absorvem até 10% do que é ingerido, em contraste com a taxa das crianças que pode chegar a 50%. Distribui-se fácil e rapidamente por todos os tecidos, além de passar a barreira encefálica e a placentária, sendo secretado no leite materno. As meias vidas de eliminação de chumbo do organismo, conforme o compartimento, podem ser resumidas da seguinte forma: sangue = 25 a 30 dias (em crianças sob exposição ambiental a baixas doses = 10 a 12meses); tecidos moles em geral = 60 dias; osso trabecular = 90 a 120 dias; osso cortical com depósitos estáveis = 25 a 30 anos. Tem ações tóxicas no sistema nervoso central, periférico, renal e hematopoiético principalmente, através de mecanismos que são discutidos no artigo.

Lead does not participate in any metabolic process in humans. Nevertheless, it is the most importantn on ferrous metal in industry since ancient times. This fact promoted a huge and extensive environmental contamination, allowing for an excessive input of lead by humans through ingestion and inhalation. In this review it is discussed aspects of kinetics and toxicity of lead in its inorganic form, being the most important chemical form presenting in occupational and general environment. As a metal, lead does not suffer biotransformation as other toxic substances. Its metabolism is limited to a complex kinetics of distribution and excretion which depends on its chemical speciation, determining the redox potential, rates of ionization and protein binding; crossing of blood brain and placental barriers; rates of tissue accumulation and renal excretion. Adults absorb 10% after lead ingestion, contrasting with children that can absorb 50%. Lead is distributed rapidly and easily through all tissues, including brain, crossing placental barrier and being secreted in maternal milk. Elimination half lifes can be very different according to the body compartment as follows: for blood = 15 to 30 days (in children under low doses of exposure = 10 to 12 months); soft tissues in general = 60 days; trabecular bone = 90 to 120 days; cortical bone with stable deposits = 25 to 30 years. Lead presents toxic action in the central and peripheral nervous system, renal and hemopoietic systems, by toxic mechanisms that are discussed in the paper.

Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1*B polymorphisms in lung cancer risk in a Brazilian population.

PURPOSE: Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (Ile) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk. PATIENTS AND METHODS: Genomic DNA was obtained from 200 Brazilian patients with LC and 264 blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study. RESULTS: No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC. CONCLUSIONS: Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC.

Environmental contamination and human exposure to lead in Brazil.

Adverse effects caused by environmental lead pollution are well recognized. Being a widespread agent in the environment and a major harmful element to organic systems, mostly to children, lead has been investigated all over the world, aiming to improve measures regarding its control. The purpose of this chapter is to present a review of the situation of production, uses, assessment of exposure, and adverse effects from environmental lead contamination in Brazil. It also presents aspects of Brazilian legislation setting up maximum permissible levels of lead in several environmental compartments such as surface and drinking water, soils, sediment, urban air, and also in commercially sold food, vegetables, fish, and meat, in an effort to control industrial emissions. Epidemiological investigations on children's lead exposure around industrial and mining areas are revised, showing that many situations where lead contamination is potentially present still need to be addressed by governmental agencies. In Brazil, lead was withdrawn from gasoline by the end of the 1980s, and the last lead mining and primary smelting plant was closed in 1995, leaving residual environmental lead contamination, which has recently been investigated using a multidisciplinary approach. Nevertheless, there are hundreds of small secondary battery recycling plants all over the country, running smelting facilities that produce local urban areas of lead contamination.

Exposição aguda à dapsona e metemoglobinemia em crianças: tratamento com doses múltiplas de carvão ativado associado ou não ao azul metileno / Acute dapsone exposure and methemoglobinemia in children: treatment with multiple doses of activated charcoal with or without the administration of methylene blue

Objetivo: Estudar a evolução da metemoglobinemia em 17 crianças com exposição aguda à dapsona, complicada com metemoglobinemia acima de 20 por cento da taxa total de hemoglobina, tratadas com doses múltiplas de carvão ativado associado ou não ao azul de metileno. Casuística e Métodos: Dezessete crianças (1-13 anos, mediana=3 anos), foram admitidas 1-72 horas após a ingestão de 100-1.200 mg (mediana = 350 mg, 10 pacientes) ou de uma quantidade desconhecida (7 pacientes) da dapsona. À admissão, o nível de metemoglobinemia variou de 23,5-49,7 por cento (mediana=37,8 por cento), e as principais manifestações clínicas observadas foram cianose (17), taquicardia (17), vômitos (11) e taquipnéia (8). Todas as crianças receberam doses múltiplas de carvão ativado por via oral ou por tubagem nasogástrica (1 g/kg,4-6x/dia, solução a 10 por cento, 3-16 doses, mediana=8doses). Em 12 pacientes também foi administrado o azul de metileno (1-2 mg/kg, solução 1-2 por cento) em dose única, IV, em torno de 5 minutos. Resultados: Constatou-se uma diminuiçao progressiva dos níveis de metemoglobinemia em ambos os grupos de tratamento (doses múltiplas de carvão ativado isoladamente ou associado ao azul de metileno. Não foi observada diferença estatística significativa, em relação à queda da metemoglobinemia de acordo com o tempo, entre os dois tipos de tratamento efetuado (p=0,49, teste de Wilcoxon). Conclusão: A administração de doses múltiplas de carvão ativado pode ser considerada como uma alternativa terapêutica, isolada ou associada ao azul de metileno, no tratamento de crianças com exposição aguda à dapsona, complicada com metemoglobinemia acima de 20 por cento da taxa de hemoglobina