Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations.

BACKGROUND: Poisonings resulting from the abuse of drugs currently represent a serious problem for public health. Among the main agents involved, cocaine stands out. It became one of the most abused drugs around the world, and one of the main reasons for visits to the emergency department due to the use of illicit substances. The use of cocaine is primarily in combination with alcoholic beverages. There are few studies that correlate cocaine blood concentration and the severity of clinical manifestations in patients evaluated at Emergency Department. The aim of the present study was to verify the possible relationship between the blood concentration of cocaine and cocaethylene (product of the interaction of cocaine with ethanol) with the severity of the clinical manifestations presented by patients with cocaine intoxication. METHODS: Blood levels were measured by high-performance liquid chromatography (HPLC) and the severity of clinical manifestations was assessed using the Stimulant Intoxication Score (SIS). To establish this relationship, Pearson's chi-square statistical test (x2) was used for categorical variables and Student's t for continuous variables, with statistical significance of 5% (p < 0.05). RESULTS: Of the 81 patients included in the study, 77.8% were men with a mean age of 32.5 years ± 8.5 and mean of SIS 3.4 ± 2.5. Considering the toxicological analysis results, 24.7% of the blood samples were positive. The mean of cocaine and cocaethylene concentrations were 0.34 µg/mL ± 0.45 and 0.38 µg/mL ± 0.34, respectively. The blood concentration of cocaine and cocaethylene has not been shown to be useful information for the treatment and prognosis of patients, but blood levels of these substances at the time of treatment, regardless of their concentration, may be an indicator of severity, showing that any concentrations of these substances should be considered as potentially toxic. CONCLUSION: The application of the SIS score proved to be an important alternative capable of predicting the severity of the patients due to cocaine intoxication in a fast and simplified way.

Multivariate analysis applied in dataset of Poison Control Center of São Paulo, Brazil.

Multivariate analysis techniques could be used to identify possible intercorrelations in intoxications cases. The statistical analyses used were a multiple logistic regression, multiple correspondence analysis, principal component and hierarchical cluster analysis. Of the 320 samples analysed, 192 samples were positive for some of the investigated toxic agents, of which 100 were positive for ethanol and 131 were positive for other substances. It was possible to group the patients into 3 clusters, which appears 66.5% of this information in the three first factorial axes. On the first axis, the male patients were separated from the female patients. Patients exposed to drugs, between 30 and 39 years old were grouped in the same cluster. On the second factorial axis, patients who were intoxicated with ethanol and who became intoxicated with diazepam were grouped. This work contributed to the mapping of intoxication cases at the Poison Control Centre of the São Paulo city, Brazil (CCI-SP) and serves as an initial study for the creation of a database that could be updated constantly and thus could provide a toxicovigilance system for educational policies.

A fast and simple approach for the quantification of 40 illicit drugs, medicines, and pesticides in blood and urine samples by UHPLC-MS/MS.

A fast and simple approach to overcome challenges in emergency toxicological analysis, using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed, for the detection of analytes in blood and urine samples from the following drug classes: analgesics, benzodiazepines, antidepressants, anticonvulsants, drugs of abuse, and pesticides. These substances are relevant in the context of emergency toxicology in Brazil. The sample preparation procedure was relatively easy and fast to perform. The method was fully validated giving limits of in the range of 0.5 and 20 ng mL-1 for blood and urine samples. The intraday and interday precision and accuracy were considered adequate for all analytes once the relative standard deviation (RSD) (%) was lower than 20% for quality control (QC) low and lower than 15% for CQ medium and high. The developed method was successfully applied to 320 real samples collected at the Poison Control Center of São Paulo, and 89.1% have shown to be positive for some of the analytes. This confirms its applicability and importance to emergency toxicological analysis, and it could be very useful in both fields of clinical and forensic toxicology.

Development of a simple HPLC-DAD multi-analyte procedure and its application in cases evaluated by the Poison Control Center of São Paulo, Brazil.

This work describes a simple approach to overcome challenges in emergency toxicological analysis, using liquid-liquid extraction and high-performance liquid chromatography coupled with a diode-array detector (HPLC-DAD). A rapid procedure has been developed, for the extraction and detection of 19 analytes from the following drug classes: analgesics, benzodiazepines, antidepressants, anticonvulsants and drugs of abuse. These substances are relevant in the context of emergency toxicology in Brazil. The method has been validated according to international guidelines by establishing parameters such as lower limit of quantification, sensitivity, linearity, accuracy and precision. The intra and inter-day precision values, at the lowest concentration levels, have always been less than 20% considering its relative standard deviation. As for accuracy values, these have also been satisfactory (above 81.3%). This method was successfully applied in 201 blood samples from patients with suspected poisoning of the Poison Control Center of São Paulo (PCC-SP), Brazil. Finally, the developed method has shown to be relevant for emergency toxicology due to its high sensitivity and it could be also very useful in both fields of clinical and forensic toxicology.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study.

Plant food supplements (PFS) are products of increasing popularity and wide-spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres-based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro-intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS-related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

Development of a method for the determination of cocaine, cocaethylene and norcocaine in human breast milk using liquid phase microextraction and gas chromatography-mass spectrometry.

Most licit and illicit substances consumed by the nursing mother might be excreted in breast milk, which may cause potential short and long term harmful effects for the breastfed infant. The extraction of substances from this matrix represents an analytical challenge due to its high protein and fat content as well as the fact that its composition changes during postpartum period. The aim of the present study was to develop a liquid phase microextraction (LPME) method for detection of the active substances: cocaine (COC), cocaethylene (CE) and norcocaine (NCOC) in human breast milk using gas chromatography-mass spectrometry (GC-MS). Validation was performed working on spiked human breast milk samples. The limits of detection (LOD) and quantification (LOQ) were of 6 and 12ng/mL, respectively, for all analytes. Calibration curves were linear over a concentration range of 12.0ng/mL-1000ng/mL (r(2)=0.99). No interferences were noticed at the retention times of interest. Within-run and between-run precision was always less or equal to 15 as % relative standard deviation, and bias ranged from 3 to 18%. Forty six milk samples were analyzed. Only one sample was confirmed to be COC positive (138ng/mL) and another one presented COC concentration near the LOD (6ng/mL). This method has shown to be a reliable alternative for the determination of cocaine, cocaethylene and norcocaine in human breast milk in the fields of clinical and forensic toxicology. LPME extraction procedure demonstrated to be a rather promising, low cost and environmental-friendly technique for the purpose of this study.

[Environmental chemical hazards and child health]. / Riscos químicos ambientais à saúde da criança.

OBJECTIVES: To review the recent medical literature on environmental chemical hazards to child health. SOURCES OF DATA: Articles published on this subject between 1999 and 2005 were searched in the MEDLINE database. Books, manuals and statements on child environmental health, issued by institutions such as the American Academy of Pediatrics and the World Health Organization, were also reviewed. SUMMARY OF THE FINDINGS: There has been a growing concern in the last few years with the exposure of children to environmental chemicals. Around 85,000 synthetic chemicals are produced today, and 2,800 of them are mass-produced. There is little knowledge regarding their effects on developing organisms. Children have a greater exposure to environmental pollutants than adults, because their metabolic needs and behaviors (e.g.: crawling, bringing objects to the mouth, playing closer to the ground) put them at special risk of contact with chemicals when they breathe, eat, drink or play. Heavy metals, pesticides, persistent organic pollutants and, at home, environmental tobacco smoke have been associated with the increasing number of diseases such as asthma, neurodevelopmental disorders and childhood cancer. CONCLUSION: Screening of risk situations using tools such as Environmental History has been stimulated alongside a greater commitment of pediatricians towards measures that can reduce the exposure of children and adolescents to environmental chemicals.

Riscos químicos ambientais à saúde da criança / Environmental chemical hazards and child health

OBJETIVO: Rever, na literatura médica recente, as informações disponíveis sobre os riscos da exposição de crianças a agentes químicos no meio ambiente. FONTES DOS DADOS: Foi realizada uma busca de artigos publicados sobre o tema na base de dados bibliográficos MEDLINE entre os anos de 1999 e 2005 e também em livros, manuais e recomendações publicados nos últimos anos por instituições como a Academia Americana de Pediatria e a Organização Mundial da Saúde, abordando saúde ambiental com foco na criança. SíNTESE DE DADOS: Nos últimos anos, observa-se uma preocupação crescente em todo o mundo com os riscos relacionados à exposição de crianças a agentes químicos presentes no meio ambiente. Em torno de 85.000 produtos químicos sintéticos são produzidos nos dias de hoje, dos quais 2.800 são considerados de alto volume de produção. Sabe-se ainda muito pouco a respeito de seus efeitos sobre organismos em desenvolvimento. Crianças, por conta de suas características fisiológicas (maior demanda de água e alimentos) e hábitos (como engatinhar, levar objetos a boca, brincar próximo ao solo) estão particularmente expostas à contaminação por agentes químicos presentes em água, ar e solo. Agentes como metais pesados, pesticidas, poluentes orgânicos persistentes e contaminantes do ambiente doméstico, como a fumaça do tabaco, têm sido cada vez mais relacionados ao aumento da ocorrência de doenças como asma, distúrbios neurológicos e comportamentais e câncer infantil. CONCLUSÃO: Estimula-se a identificação de situações de risco utilizando instrumentos como a anamnese ou história ambiental, bem como o envolvimento dos pediatras na busca da redução da exposição de crianças e adolescentes a agentes químicos.

Episodic somnolence in an infant with Riley-Day syndrome.

Familial dysautonomia is an autosomal recessive congenital neuropathy that occurs almost exclusively in the Ashkenazi Jewish population and has rarely been diagnosed in the neonatal period in unaffected families. This report describes a patient who, during the neonatal period, had episodes of marked decrease in the level of consciousness with durations of 4-15 hours. Other signs and symptoms included the absence of fungiform papillae of the tongue, areflexia, and failure to thrive. The diagnosis was confirmed by the demonstration of mutations in the IkappaB kinase complex-associated protein gene with the identification of IVS20 (+6T --> C) which is responsible for more than 99.5% of known Ashkenazi Jewish patients with familial dysautonomia. The prognosis of this disease and the possibility of genetic counseling are clearly related with an early definitive diagnosis, and this patient illustrates the importance of episodes of somnolence as a possible sign of familial dysautonomia.