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Comment in:
Paralytic rabies after a two week holiday in India.
Solomon T, Marston D, Mallewa M, Felton T, Shaw S, McElhinney LM, Das K, Mansfield K, Wainwright J, Kwong GN, Fooks AR.
Viral CNS Infections Group, Division of Neurological Science, University of Liverpool, Walton Centre for Neurology and Neurosurgery, Liverpool L9 7LJ. tsolomon@liv.ac.uk
Publication Types:
PMID: 16141158 [PubMed - indexed for MEDLINE]
Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values.
Goulle JP, Mahieu L, Castermant J, Neveu N, Bonneau L, Laine G, Bouige D, Lacroix C.
Laboratoire de Pharmacocinetique et de Toxicologie Cliniques, Groupe Hospitalier, BP 24, 76083 Le Havre, France. jgoulle@ch-havre.fr
Four multi-elementary metal and metalloid quantification methods using inductively coupled plasma mass spectrometry (ICP-MS) were developed and validated in human whole blood, plasma, urine and hair by means of a single preparation procedure for each sample. The ICP-MS measurements were performed using a Thermo Elemental X7CCT series and PlasmaLab software without a dynamic reaction cell. With this procedure 27-32 elements can be simultaneously quantified in biological matrices: Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, Pb, Bi, U. Whole blood, plasma and urine samples (0.4 ml each) were diluted with purified water, acid, triton X100 and butanol. Rhodium was used as internal standard. The urine sample results were corrected for enzymatic creatinine determination. Twenty-five milligrams hair samples were acid mineralized after a decontamination procedure and diluted as previously described for biological fluids. To be validated, each element had to show linearity with a correlation coefficient higher than 0.99. The intra-assay and inter-assay inaccuracy, measured as the variation coefficient, were below 5 and 10% respectively. Global performance was assessed by a quality control program. Our laboratory is a registered participant of the Institut National de Sante Publique du Quebec (Sainte-Foy, Canada) inter-laboratory comparison program for whole blood, urine, and beard hair of non-occupationally exposed individuals spiked with selected elements. In our study multi-element metal and metalloid analysis was assessed for 27 elements in whole blood, 27 elements in plasma, 30 elements in urine and 32 elements in hair, from 0 to 25, or 250 to 1000 ng/ml, depending on the element. Quantification limits ranged from 0.002 ng/ml (U) to 8.1 ng/ml (Al) for whole blood, from 0.002 ng/ml (U) to 7.7 ng/ml (Al) for plasma, from 0.001 ng/ml (U) to 2.2 ng/ml (Se) for urine, and from 0.2 pg/mg (Tl) to 0.5 ng/mg (B) for hair. Normal values were determined in whole blood (n=100), plasma (n=100), urine (n=100), and hair (n=45) of healthy volunteers, leading to approximately 10,000 analyses. All results are presented and discussed. Clinical toxicology and forensic toxicology applications are also reported. ICP-MS has made significant advances in the field of clinical biology, particularly in toxicological analysis. This is due to the use of extremely effective equipment that permits better clinical and forensic toxicological analysis of metal and metalloid status of each individual patient.
PMID: 15979835 [PubMed - indexed for MEDLINE]
Clinical parameters, postmortem analysis and estimation of lethal dose in victims of a massive intoxication with diethylene glycol.
Ferrari LA, Giannuzzi L.
Laboratory of Toxicology and Legal Chemistry, Court of Justice of the Province of Buenos Aires, 41 and 119, 1900 La Plata, Argentina. laferrari@unimoron.edu.ar
This work analyzes a massive intoxication that occurred in 1992 in Argentina as a result of the use of propolis syrup as a popular upper respiratory infection medicinal agent. The intoxicating agent was diethylene glycol (DEG), which caused metabolic acidosis, anuria, renal failure and death in 15 out of the 29 studied victims. DEG poisoning cases were classified in three groups according to survival time: Group 1-patients that survived up to 3 days; Group 2-patients that survived between 4 and 5 days; Group 3-patients that survived between 6 and 21 days. Patients from Group 1 showed the highest values of anion gap, the lowest measures of base excess (BE) and more severe clinical manifestations. Correlation between pH and BE was r(2) = 0.68, 0.99 and 0.55 for Groups 1, 2 and 3, respectively. A methanolic extraction was performed on the fatal victims' viscera and blood, with subsequent concentration and purification. The semi-crystalline fraction obtained retained DEG by means of co-dissolution and adsorption as demonstrated by thin lay chromatography/flame ionisation detection (TLC/FID). In 3 out of the 15 fatal cases (from Group 1), DEG was isolated from viscera and blood (femoral venous), between 48 and 72 h post ingestion. The concentration relation (DEG)viscera/(DEG)blood ranged from 1.45 to 1.55 with a coefficient correlation r(2)=0.96 (n=3). In the other victims, DEG could not be detected. The reason for this could be the long survival period of the victims after their ingestion of the syrup. Additionally, putrefying mechanisms could have been operating. Samples of the propolis syrup of each victim were studied by means of nuclear magnetic resonance (NMR) and quantified by gas chromatography/flame ionisation detection (GC/FID). Results showed that syrup samples contained 65.0% (w/v) of diethylene glycol (DEG) and 32.0% (w/v) of propylene glycol (PG). A good correlation between the amount of DEG ingested and the anion gap (r(2)=0.63) for the 15 victims studied could be observed. The lethal dose for human beings estimated in this work ranged from 0.014 to 0.170 mg DEG/kg body weight. This is a lower lethal dose than reported in a separate incident in Haiti. These results may contribute to the understanding of DEG's metabolic pathway and provides data from lethal doses in humans.
PMID: 15979833 [PubMed - indexed for MEDLINE]
Methcathinone: a new postindustrial drug.
Belhadj-Tahar H, Sadeg N.
Groupe Sante Recherche, 35 rue Bernard de Ventadour, 31300 Toulouse, France. belhadj.h@oreka.com
Methcathinone, a methyl derivative of cathinone, is an illicit drug also known as ephedrone. It is a stimulant found in the "khat" plant, Catha edulis, which can easily be synthesized from pseudoephedrine. Its intoxication is difficult to diagnose and cure properly for two reasons: (i) target consumers are usually "well-educated people" aware of the risks and precautionary measures and (ii) intoxication by cathinone derivatives of synthetic or natural (derived from the khat) origin induce misleading symptoms. As a result, documented reports of methcathinone intoxication that are based on reliable analyses are rare. This paper describes a case of reiterated coma due to an overdose of methcathinone dissolved in alcohol that was taken with bromazepam. A 29-year-old woman was admitted to an emergency department for a coma of toxic origin. Medical files showed that it was her second such episode to occur that month. Moreover, the family indicated signs of depression, incoherent behaviour and intake of "amphetamine-like" drugs. Clinical examination revealed a Glasgow coma score of 9, symmetrical reactive pupils with mydriasis and no convulsions. The patient presented with rapid respirations and her blood pressure was 93/53 mmHg. The ionogram and the blood gas analyses were normal, while the blood alcohol level was 0.167 g/dL. Urinalysis revealed the presence of benzodiazepines and a high concentration of amphetamines (methcathinone: 17.24 mg/L, ephedrine: 11.60 mg/L and methylephedrine: 11.10 mg/L). In addition, serum analysis revealed bromazepam (8.89 mg/L), methcathinone (0.50 mg/L) and methylephedrine (0.19 mg/L). This case showed that the consumption of bromazepam and alcohol altered the typical clinical symptoms of cathinone derivative intoxication, namely hypertension and convulsions. Methylephedrine, an impurity resulting from the alkylation of a primary amine, can be considered a chemical tag indicating fraudulent synthetic origin of the drug. This case describes a documented example of new addictive behaviour of "well-educated" people involving the intake of methcathinone, a postindustrial psychostimulant intentionally combined with an anticonvulsant benzodiazepine. However, this specific case suggests that in spite of a very high bromazepam concentration in presence of the potentiator alcohol, the vital respiratory function would be probably maintained, thanks to the association with methcathinone.
Publication Types:
PMID: 15919169 [PubMed - indexed for MEDLINE]
Poison Control Center--based syndromic surveillance for foodborne illness.
Derby MP, McNally J, Ranger-Moore J, Hulette L, Villar R, Hysong T, MacNeill E, Lebowitz M, Burgess J.
Environmental and Community Health, Mel and Enid Zuckerman College of Public Health, The University of Arizona, Tucson, Arizona 85719, USA. mpderby@email.arizona.edu
OBJECTIVES: This retrospective study evaluated the usefulness of a poison control center (PCC) data collection system in Tucson, Arizona for early detection of foodborne disease outbreaks. METHODS: A search of a PCC database identified callers with gastrointestinal symptoms attributable to suspected foodborne illnesses whose calls were received during January 1-March 31, 2000. For each foodborne illness-related call, PCC coding was compared with a predefined diarrhea/gastroenteritis syndrome. PCC calls also were evaluated by using ZIP code, age, sex, and date of symptom onset to determine if call classifications matched any laboratory-confirmed cases reported to a county health department. RESULTS: An independent review generally agreed with the PCC's classification of calls. When calls and cases were compared, only one potential match was identified. CONCLUSION: Although confirmatory diagnostic information was not available, PCC calls were not duplicative of cases evaluated by the county health department, which suggests that they represent two independent data sets. PCC data might provide a useful addition to surveillance data reported to public health agencies for the early detection of foodborne disease outbreaks. These results will now be used to develop collaborative prospective surveillance systems.
PMID: 16177691 [PubMed - indexed for MEDLINE]
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Improper disposal of hazardous substances and resulting injuries--selected States, January 2001-March 2005.
Centers for Disease Control and Prevention (CDC).
Many consumer and industrial products, including fuels, solvents, fertilizers, pesticides, paints, and household cleaning disinfectants, contain hazardous substances. Improper disposal of these materials can lead to unexpected releases of toxins that are hazardous to humans and harmful to the environment. This report summarizes all known events involving improper disposal of hazardous substances reported to the Agency for Toxic Substances and Disease Registry (ATSDR) during January 2001-March 2005, describes four illustrative case reports, and provides recommendations for preventing injury resulting from improper disposal.
Publication Types:
PMID: 16163263 [PubMed - indexed for MEDLINE]
Epidemic cat-transmitted sporotrichosis.
Schubach AO, Schubach TM, Barros MB.
Publication Types:
PMID: 16162897 [PubMed - indexed for MEDLINE]
Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis.
Heijne WH, Lamers RJ, van Bladeren PJ, Groten JP, van Nesselrooij JH, van Ommen B.
TNO Nutrition and Food Research, 3700 AJ Zeist, The Netherlands. Heijne@pharma.TNO.nl
This study investigated whether integrated analysis of transcriptomics and metabolomics data increased the sensitivity of detection and provided new insight in the mechanisms of hepatotoxicity. Metabolite levels in plasma or urine were analyzed in relation to changes in hepatic gene expression in rats that received bromobenzene to induce acute hepatic centrilobular necrosis. Bromobenzene-induced lesions were only observed after treatment with the highest of 3 dose levels. Multivariate statistical analysis showed that metabolite profiles of blood plasma were largely different from controls when the rats were treated with bromobenzene, also at doses that did not elicit histopathological changes. Changes in levels of genes and metabolites were related to the degree of necrosis, providing putative novel markers of hepatotoxicity. Levels of endogenous metabolites like alanine, lactate, tyrosine and dimethylglycine differed in plasma from treated and control rats. The metabolite profiles of urine were found to be reflective of the exposure levels. This integrated analysis of hepatic transcriptomics and plasma metabolomics was able to more sensitively detect changes related to hepatotoxicity and discover novel markers. The relation between gene expression and metabolite levels was explored and additional insight in the role of various biological pathways in bromobenzene-induced hepatic necrosis was obtained, including the involvement of apoptosis and changes in glycolysis and amino acid metabolism.The complete Table 2 is available as a supplemental file online at http://taylorandfrancis.metapress.com/openurlasp?genre=journal&issn=0192-6233. To access the file, click on the issue link for 33(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org.
PMID: 16036859 [PubMed - indexed for MEDLINE]
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