Prevention of isoniazid toxicity by NAT2 genotyping in Senegalese tuberculosis patients.

Isoniazid (INH), recommended by WHO (World Health Organization) in the treatment of tuberculosis (TB), is metabolized primarily by the genetically polymorphic N-acetyltransferase 2 (NAT2) enzyme. The human population is divided into three different phenotypic groups according to acetylation rate: slow, intermediate, and fast acetylators. The objective of this study was to explore the relationship between NAT2 genotypes and the serum concentrations of INH. Blood samples from 96 patients with TB were taken for the analysis. NAT2 polymorphisms on coding region were examined by polymerase chain reaction (PCR) direct sequencing; the acetylation status was obtained by measuring isoniazid (INH) and its metabolite, acetylisoniazid (AcINH) in plasma was obtained by using the liquid chromatography coupled to mass spectrometry. TB patients were distributed into two groups of fast and slow acetylators according to the acetylation index calculated based on the plasma concentration of INH in the 3rd hour (T3) after an oral dose. Our PCR analysis identified several alleles, where NAT2*4, NAT2*5A, NAT2*6A, and NAT2*13A were the most important. The concentrations of INH varied between 1.10 mg/L and 13.10 mg/L at the 3rd hour and between 0.1 and 9.5 mg/L at the 6th hour. The use of the acetylating index I3 allowed the classification of tested patients into two phenotypic groups: slow acetylators (44.3% of TB patients), and rapid acetylators (55.7%). Patient's acetylation profile provides valuable information on their therapeutic, pharmacological, and toxicological responses.

[Anti-aging medicine, a science-based, essential medicine]. / La médecine anti-âge, une médecine scientifique, indispensable.

Anti-aging medicine is booming. It enters more and more in the programs of universities. Its hormone and nutritional tests and therapies rely on numerous scientific studies, including double-blind placebo-controlled randomized studies. Its methods are often innovative to obtain more information or benefits with greater safety. The fundamental purpose of anti-aging medicine is to optimize health and the quality of life, and through this, make the physical appearance more youthful. Well-chosen and well-dosed these treatments should not increase the risk of age-related diseases such as cancer and cardiovascular diseases, but on the contrary decrease it by the preventive aspect of the treatments. Opponents to anti-aging medicine fail in collecting valid scientific arguments. Their insistence on maintaining a society of elderly people looking and feeling as elderly people rather than actively participating in searching for ways to attenuate aging is harmful to all who follow them, to themselves in the first place.

Study of NAT2 genetic polymorphism in West African subjects: example of an healthy non-smoker Senegalese population.

The NAT2 genetic polymorphism determines the individual acetylator status and, consequently, the capacity to metabolize, or not, drugs and xenobiotics which are substrates of NAT2. As the nature and frequency of the NAT2 polymorphisms vary remarkably between populations of different ethnic origins, genotyping strategies used to predict the acetylation phenotype need to be adapted for each particular population regarding their genetic backgrounds at this locus. As few data on the genetic polymorphism of NAT2 are available in the Senegalese population, we performed an extensive identification of NAT2 variants in 105 healthy non-smoker Senegalese subjects by direct PCR sequencing of the coding region. Eleven previously described SNPs were identified in this Senegalese population. Upon allele analysis, the four most frequent alleles were of the NAT2*5- (35.7 %), NAT2*6- (21.0 %), NAT2*12- (16.7 %) and NAT2*14- (10.0 %) type, the remaining alleles, including the wild-type NAT2*4, having each a frequency lower than 10 %. According to the observed genotypes, 51 and 50 subjects were predicted to be of the rapid (48.6 %) and slow (47.6 %) acetylator phenotype, respectively, while four individuals (3.8 %) were considered of unknown phenotype as they carry at least one allele with a yet unknown functional effect. These baseline data would be of particular interest to set up an efficient genotyping strategy to predict the acetylation status of Senegalese patients with tuberculosis and, thus, to optimize their isoniazid treatment.

[Use of illicit substances in the workplace]. / Consommation de substances illicites en milieu professionnel.

The development of addictive behaviors is a source of worry and concern for workplace and occupational physicians. To estimate the prevalence of behaviors, two types of surveys can be carried out: self-assessment surveys and biological testing in the workplace. For the latter, when a settlement is within the company, the prevalence is often lower compared to those enterprises that have not adapted this policy. Very few investigations have been published in France to date. Data published by the United Nations Office against Drugs and Crime (UNODC) shows a stable consumption of illicit substances in recent years. They reported consumption in the world among the general population (all subjects aged 15 to 64). For France, were described a prevalence estimated in 2005 to 8.6%, 0.6% and 0.2% for cannabis, cocaine and amphetamine derivatives, respectively, and in 2007 to 4.6% for opiates. Some prevalence in the workplace have been reported in Europe in chemical, petrochemical, metallurgical, automotive, in the transport sector and in medical and military fields. However, it appears that few surveys in the workplace have been published in France, this lack may be explained by a desire for anonymity on the subject at the level of company management and doctors work that focus on individual support with the problem of addiction. Screening for illicit substances is necessary because these psychotropic substances affect alertness and pose risks in the workplace, especially such that the association cannabis-alcohol further increases the risk. Knowledge of consumption is, moreover, an important factor in job security. It may be acquired if reliable methods, inexpensive to allow routine screening. Publication of results will reveal the extent of the problem and implement more effective campaigns of information and prevention in the workplace.

Drugs involved in drug-facilitated crimes--part II: Drugs of abuse, prescription and over-the-counter medications. A review.

In recent years, there has been a notable increase in the number of reports of drug-facilitated crimes. Usually, individuals report that they were robbed or assaulted while incapacitated by drugs. Most often, these cases have involved drugs that have the ability to produce an effect that leaves the victim in a semiconscious or unconscious state. It is reasonable to assume that the purpose of drug-induced incapacitation is probably largely unchanged with time. This covers the full range of property offences (particularly theft) and crimes against the person (often sexual assault). What have changed are the drugs themselves: the number; type; their accessibility; effects and detection. This review describes the different aspects related to the involvement and use of drugs of abuse, as well as prescription and over-the counter medications in drug-facilitated crimes, which may help people working in this field to expand their knowledge in order to better understand the nature of these crimes or offences.

Drugs involved in drug-facilitated crimes: part I: alcohol, sedative-hypnotic drugs, gamma-hydroxybutyrate and ketamine. A review.

SUMMARY: In recent years, there has been a notable increase in the number of reports of drug-facilitated crimes (DFCs). Usually, individuals report that they were robbed or assaulted while incapacitated by drugs. Most often, these cases have involved drugs that have the ability to produce an effect that leaves the victim in a semiconscious or unconscious state. It is reasonable to assume that the purpose of drug-induced incapacitation is probably largely unchanged with time. This covers the full range of property offences (particularly theft) and crimes against the person. What have changed are the drugs themselves: the number; type; their accessibility; effects and detection. The purpose of this review is to explore the different aspects related to the involvement and use of ethanol, sedative-hypnotics drugs, gamma-hydroxybutyrate (GHB) and ketamine in DFCs or offences, which may help people working in this field to expand their knowledge for better understanding of the nature of these crimes or offences.

Drug-facilitated crimes: definitions, prevalence, difficulties and recommendations. A review.

Drug-facilitated crimes are not a new phenomenon but rather an age-old practice. However, reports of drug-facilitated crimes have significantly increased since the mid-1990s. Victims of these crimes or offences report that they were robbed or assaulted while incapacitated by a drug. Most often, these cases have involved strong central nervous system depressant drugs, which have the capability of preventing individuals from consenting to the action of the perpetrator of fighting off their attackers. For all intents and purposes, the drug acts as the offender's weapon, therefore many jurisdictions require analytical proof of its presence, which helps substantiate the alleged victim's claim. This review was undertaken to identify the evolutionary process in the current understanding of allegations of these crimes or offences, so that whoever works in this field may gain a better understanding of the complexities involved in such cases. This review provides several definitions of drug-facilitated crimes, their prevalence in European and English-speaking countries, a list of intoxicating substances, which have so far been incriminated or been suspected to be involved in these crimes or offences, some of the more common difficulties encountered in the investigation, and recommendations to improve detection of the drugs through toxicological analyses.

[Impact of interferon alpha immunotherapy on tryptophan metabolism in patients with chronic hepatitis C. Results of a pilot studies on ten patients]. / Impact du traitement par interféron alpha sur le métabolisme du tryptophane chez des patients porteurs d'hépatite C chronique Résultats de la phase d'étude pilote sur dix patients.

INTRODUCTION: The proinflammatory cytokine interferon (IFN) alpha is commonly used in the treatment of patients with hepatitis C but its administration is often responsible for neuropsychiatric side effects (low mood, fatigue, sleep-wake disorders, irritability and weight loss). Various mechanisms have been incriminated to explain the production of depression and anxiety symptoms, among which serotonergic hypothesis is supported by a growing body of evidence. The latter posits that IFN-alpha is responsible for central serotonin (5-HT) depletion by deviating its precursor, tryptophan (TRP), to a catabolic kynurenine (KYN) pathway through induction of indoleamine 2.3 dioxygenase (IDO). The aim of the study was to examine the time variation of 5-HT blood (serum and platelet) levels and serum KYN/TRP ratio along with instauration of IFN-alpha therapy and to correlate these biological variations with mood fluctuations. METHOD: Patients. Ten patients (mean [S.D.] age 45 years [12.7], range 29-63; three males, seven females) with chronic hepatitis C eligible to receive IFN-alpha (1.5microg/kg/week Viraferon, Schering-Plough, administered subcutaneously) were recruited from the Gastroenterology department of the University hospital of Lille, France. Patients with cirrhosis, HIV or hepatitis B or D co-infection, persistent intravenous addiction, corticoid therapy or any DSM-IV axis 1 psychiatric disorder (diagnosed with MINI interview) were excluded. Patients with chronic active hepatitis C were assessed at baseline and monthly during the first semester of IFN-alpha and ribavirine bi-therapy. Measurements. The Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) were used to assess depression and anxiety fluctuations. Serum and platelet serotonin levels were determined by HPLC with coulometric detection. Simultaneous quantification of TRP and KYN was determined by means of HPLC with fluorescence detection (TRP) or UV detection (KYN). Statistics. TRP, KYN concentrations and KYN/TRP ratio as well as MADRS and HAM-A measurements were performed at three time points (day 1, weeks 4 and 12) of IFN-alpha therapy. Analysis of variance used a linear model (with subject as the random factor) and correlation between measurements used an autoregressive model of order 1. For all probabilities, the level of significance was set at P<.05. RESULTS: Two patients were excluded before the first post-treatment assessment (results not shown). In the eight remaining patients, we observed significant increase of KYN/TRP ratio from baseline to early (week 4) and late (week 12) assessments (respectively, mean [S.D.] 5.57[5.24], 13.52[15.53] and 29.78[14.11], with P=.04). Similarly, significant increase in the MADRS (respectively 7.13[5.2], 12[6.9] and 16.6[8.6], with P=.03) and HAM-A (respectively 9.25[6.27], 15.1[6.95] and 18.7[6.27], with P=.02) mean scores were observed. Serum and platelet serotonin levels showed no significant variation with time. CONCLUSION: The results are consistent with the physiopathological hypothesis of an induction of IDO underlying depressive and anxiety symptoms related to IFN-alpha therapy in patients with chronic active hepatitis C. Nevertheless, this pilot study allows no firm conclusion since sample effective is weak and delay between IFN-alpha weekly injection and psychiatric and biological assessment was not controlled and thus may have biased our findings. However, these encouraging results advocate for further exploration of tryptophan metabolism for a better understanding of individual vulnerability to IFN-alpha-induced psychiatric adverse effects.

Hair analysis by LC-MS as evidence of nalbuphine abuse by a nurse.

Individuals in any profession can succumb to chemical abuse. Among the healthcare profession, nurses represent a specific group because of their ease of access to drugs, particularly narcotics. Opioids, potentially highly addictive agents, are usually their drug of choice. Nalbuphine, a synthetic opioid analgesic, is prescribed for moderate-to-severe acute pain, for chronic pain syndromes, and in obstetrics to decrease the adverse respiratory effect of opioid epidural administration. The case of a nurse who was suspected of drug misuse after the disappearance of two nalbuphine ampules in an obstetrics service is described. Because of discrepancies in the results of her blood and urine samples, a sample of head hair was subsequently collected from the nurse. A hair analysis of nalbuphine by liquid chromatography-mass spectrometry has not been previously described. Following decontamination and grinding, hair was mixed with a Söerensen buffer, then subjected to ultrasonic treatment (1 h), and extracted with ethyl acetate. A quantitative analysis was performed with two channels (30 and 45 V), and it is based on a m/z 358 for nalbuphine and a m/z 330 for methylclonazepam as an internal standard. The method was linear from 0.020 to 12 ng/mg of hair (R(2) = 0.972), and the limit of detection and limit of quantitation are 0.020 ng/mg. Accuracy (CV), assessed at 0.4 and 1.6 ng/mg of hair, was 6.18% and 5.77%, respectively, for intraday assays and 4.5% and 10.9% for interday assays. Recovery efficiency at 1.6 ng/mg and 8 ng/mg of hair was 100% and 97.4%, respectively. The hair specimen from the nurse (6 cm) was cut into three equal lengths. Nalbuphine, venlafaxine, and nordiazepam were detected. The concentration of nalbuphine was similar in the three hair locks: 5.07, 7.06, and 5.70 ng/mg of hair. A hair analysis revealed the repeated intake of nalbuphine by the nurse. This person was treated for depression for several months with Effexor (venlafaxine) and Nordaz (nordiazepam) prior to the investigation. Hair appears to be a unique matrix to provide evidence for chronic drug exposure by establishing a historic record that is not possible by blood or urine analysis.

Ethnic differences in the distribution of CYP3A5 gene polymorphisms.

The genetic polymorphism affecting the CYP3A5 enzyme is responsible for interindividual and interethnic variability in the metabolism of CYP3A5 substrates. The full extent of the CYP3A5 genetic polymorphism was analysed in French Caucasian, Gabonese and Tunisian populations using a polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) strategy. In the three populations, eight, 17 and ten single nucleotide polymorphisms (SNPs), respectively, were identified, among which nine correspond to rare new mutations. Also identified were 16 alleles including eight new allelic variants. Significant differences were observed in the distribution of these alleles. Particularly, the frequency of the CYP3A5*3C null allele in French Caucasians (81.3%) and in Tunisians (80.0%) is higher than in the Gabonese population (12.5%) (p < 0.001). Considering the CYP3A5 genotypes of the tested individuals, only 10.4% of French Caucasians and 30.0% of Tunisians were identified as CYP3A5 expressors. In contrast, 90.0% of Gabonese subjects appear to express the CYP3A5 protein.

[Therapeutic failure: importance of genes?]. / Echec thérapeutique: peut-être une affaire de gènes?

Drug management can be a difficult task in certain situations because of the variable response observed from one patient to another. Genetic factors affecting the pharmacokinetics and pharmacodynamics of drug reactions could explain the interindividual variability in drug response. Pharmacogenetic analysis provides insight into the molecular mechanisms involved in drug response, with the ultimate goal of achieving optimal drug efficacy and safety. Numerous polymorphisms have been described in genes encoding drug-metabolising enzymes, transporters, and receptors. For some drugs, the impact on drug bioavailability and effect has been elucidated. We review here the molecular basis of interindividual variation in drug response and the methods used to identify individual risk of drug failure or toxicity. Clinical applications, concerning enzymes metabolising drugs (cytochrome P4502D6, thiopurine S-methyltransferase and N-acetyltransferase) provide an illustrative demonstration of the usefulness of pharmacogenetic tests in improving patient management. Clinical validation of these tests and new technologies (real-time PCR, DNA chips) should, in the future promote pharmacogenetics in clinical practice and may be lead to more individualized drug therapy.

Factors associated with perceived exertion and estimated time limit at lactate threshold.

The purpose was to identify the most predictive parameters for perceived exertion and estimated time limit responses at the velocity corresponding to the lactate concentration threshold. The former scale concerns the subject's current status (how hard he feels the exercise currently is) whereas the latter scale deals with a subjective prediction of how long the current exercise level can be maintained. Multiple regression equations were developed among physiological, psychological, nutritional, and individual parameters (subjects' characteristics and performances) as independent variables, and perceived exertion or estimated time limit as dependent variables. Independent variables were collected before or during an incremental running field test. 94 regional to national level athletes (47 endurance-trained runners, 11 sprinters, and 36 handball players) participated. Multiple stepwise regression showed that Rating of Perceived Exertion and Estimated Time Limit at the lactate threshold were mainly mediated by factors relative to the performance expressed in percentage of the maximal aerobic velocity. Secondary factors which contribute significantly as perceptual predictors were related to various classes of factors except for psychological factors.

[Assessment of occupational exposure to ortho-toluidine using gas chromatography-mass spectrometry]. / Evaluation d'une exposition professionnelle à l'ortho-toluidine par chromatographie phase gazeuse couplée a la spectrométrie de masse.

Ortho-toluidine is a carcinogen aromatic amine. It is in part eliminated as unchanged form and its urine determination allows biologic monitoriing of occupational exposure. We propose a new method simple and fast in gas chromatography mass spectrometry. In the Nord-Pas-de-Calais region, a company initiated destruction and depollution of an old industrialsite.The GS-MS method permits exposition evaluation of workers employed in demolition of a liquid SO2 plant polluted with ortho-toluidine. This plant has been stopped twenty years ago. These results are compared with results of workers without any exposure in the same company. A 5 mL urine sample spiked with internal standard (ortho-toluidine D9) is extracted with hexane. Derivatisation is achieved with anhydrous pentafluoropropionic acid during 30 min at 60 degrees C. Chromatographic separation is performed on a BPX5MS column (25 m x 0.25 mm, 0.25 microm; SGE). Initial column temperature (60 degrees C) is hold 3 min then is raised to 300 degrees C at 25 degrees C/min. Detection is performed with mass spectrometry with negative chemical ionisation with methane. Acquisition is performed in single ion monitoring. Identification ions are 233 ion (m/z) and 213 ion (m/z) with 233 (m/z) used for quantification. Linearity of the method is verified between 0.1 and 100 microg/L. The limit of detection is 0.02 micro/L. Repeatability and intermediate fidelity are satisfactory (CV < 9%). For unexposed workers, urinary concentrations of ortho-toluidine ranged between 0.17 microg/L and 2.46 microg/g creatinine. Urinary concentrations for exposed workers ranged between 26.14 and 462.00 microg/g creatinine and after new action of protection between 2.35 et 20.11 microg/g creatinine. This new GC-MS method is specific and sensitive and allows for urinary determination of ortho-toluidine. Results showed that this method is adapted for biomonitoring as much for unexposed workers to this aromatic amine as for exposed workers.

Use of drugs of abuse in less than 30-year-old drivers killed in a road crash in France: a spectacular increase for cannabis, cocaine and amphetamines.

A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.

Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms.

OBJECTIVE: To develop a model based on mean residence time for better understanding the effect of grapefruit juice on the metabolism of nifedipine (NIF). MATERIAL AND METHODS: Sixteen healthy volunteers from an urban population were included. For each trial, the subjects drank water, fresh grapefruit juice or bottled grapefruit juice. Thirty minutes later, the subjects took a 10 mg capsule of NIF, orally. Plasma concentration of NIF was measured and the kinetic parameters were calculated with a non-compartmental model. RESULTS: Grapefruit juice increased the bioavailability of NIF, but did not significantly reduce the drug's metabolism as shown by the approximately constant metabolite to parent drug AUC ratio (P = 0.948). There was no significant increase in the amount of non-metabolized drug absorbed during first-pass: 0.12 and 0.16 (P = 0.470) without and with grapefruit juices respectively. There was an increase in the relative bioavailability (P = 0.039) and the apparent volume of distribution (Vdm) (P = 0.025) of dehydronifedipine with grapefruit co-administration. A second peak was also observed in the NIF plasma-concentration profile when the drug is co-administered with grapefruit juice. Therefore, the most likely explanation for the double peak phenomenon is a delay in gastric emptying (+32 min with grapefruit juice) caused by the pH of grapefruit juice. CONCLUSION: This study shows that grapefruit juice interferes with the metabolism of NIF by inhibiting NIF metabolism and slowing down the rate of gastric emptying. This study also confirms that the metabolic inhibition is not a first pass effect, but is a secondary oxidative step.

Influence of acetaminophen consumption on perceived exertion at the lactate concentration threshold.

The purpose of this investigation was to study effects of acetaminophen consumption on ratings of perceived exertion and estimated time limit responses at the lactate threshold. 98 young regional to national level athletes performed a graded exhausting exercise on an outdoor running track to estimate their maximal aerobic velocity and the velocity associated with their lactate concentration threshold. Urine (30 mL) was collected during this test and analysed for numerous substances. During urinary screening for doping substances, 9 acetaminophen consumers (9.2%) among the 98 included athletes were detected. These acetaminophen consumers have significantly lower perceived exertion at velocity corresponding to the lactate concentration threshold than nonconsumers (11.9 +/- 2.1 vs 13.6 +/- 2.1, respectively) although they were at the same relative exercise intensity. This result shows that acetaminophen consumption may have mediated the perceived exertion response at the lactate concentration threshold. This may then suggest that the pain induced by training load could be a factor in use of self-prescribed pain relievers. Such consumption must be taken into account by medical staff, trainers, or educators who have to give information on the use and adverse effects of this substance and to propose palliative methods to their athletes.

Simultaneous determination of tryptophan and kynurenine in serum by HPLC with UV and fluorescence detection.

Tryptophan metabolism is disturbed in mental depression, and the induction of indoleamine 2,3-dioxygenase increases kynurenine production. In order to determine this disturbance in patients with chronic hepatitis C and receiving interferon-based immunotherapy, a new and specific HPLC protocol was elaborated. For tryptophan, the assay was linear from 6.25 to 100 micromol L(-1), and the limits of detection (LOD) and quantitation (LOQ) for the method were 0.7 and 8.0 micromol L(-1). For kynurenine, the linearity of calibration was from 0.0625 to 6.25 micromol L(-1), with LOD and LOQ of 2 and 3 nmol L(-1). Reproducibility and repeatability were satisfactory. The method allowed study of human blood serum.

Determination of glyphosate in biological fluids by 1H and 31P NMR spectroscopy.

Identification of glyphosate in four cases of poisoning, using nuclear magnetic resonance spectroscopy of biological fluids is reported. It has been performed by using a combination of 1H and 31P NMR analyses. Characterization of the N-(phosphonomethyl) glycine herbicide was achieved by chemical shift considerations and coupling constant patterns: CH2-(P) presents specific resonance at 3.12 ppm and appears as a doublet with a H-P characteristic coupling constant of 12.3 Hz. Moreover, resonances due to isopropylamine were present, confirming the ingestion of the considered trade formulation. After a calibration step, quantitation was performed by 1H and 31P NMR spectroscopy. The benefit and reliability of NMR investigations of biological fluids are discussed, particularly when the clinical picture is quite confusing.

A fatal case of mercuric cyanide poisoning.

A 57-year-old pharmacist was found dead 11 days after his disappearance. At the autopsy, samples of blood, urine, gastric content were obtained. Presence of ethanol, cyanide and mercury were detected in some samples. Cyanide and mercury were identified and quantified using high-performance liquid chromatography with diode array detector (HPLC) in fluorescence mode and ICP with mass selective detector (ICP-MS) respectively. Whole blood concentrations of ethanol was 1.72 g/L. Cyanide and mercury concentrations in whole blood were respectively 0.16 and 3.8 mg/L. Concentrations of cyanide (27 mg/L) and mercury (150 mg/L) in gastric contents prove a massive oral ingestion of mercuric cyanide or mercuric oxycyanide occurred. In this case report, the death was attributed to the combined toxicity of cyanide and mercury.

[Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination]. / Biomarqueurs de toxicité et anomalies métaboliques dans les principales intoxications graves. Symptomatologie clinique et toxique. Le prélèvement conservatoire.

The members of the joint group "Toxicology and Clinical Biology" of the French Society of Clinical Biology (SFBC), the French Society of Analytical Toxicology (SFTA), and the Society of Clinical Toxicology (STC), suggest guidelines to meet the requirements of clinical biologists who are not specialized in toxicology. Based on good laboratory practice they propose a number of guidelines. Three synthetic tables have been established. They are not only toxicity biomarkers and metabolic disorders associated with the main severe intoxications, but also clinical signs that are observed during these intoxications, finally biological sampling as a precautionary measure. The table also takes into account approximately fifty xenobiotics: main clinical signs emergency, identification or quantification of the suspected product, useful biological markers, therapeutic, quantitations necessary to take into consideration patient care, and poison antidotes, are described. Recommendations regarding medical and forensic techniques are also proposed by the group. It is also necessary to collect and store biological samples when the individual patients are in charge. These samples will be analyzed or not depending on the individual case history.