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Biomedical subjects

Patrice Mangin

Publications and source records attributed to Patrice Mangin.

32 records · Page 2Linked to original sources

[13C]Nandrolone excretion in trained athletes: interindividual variability in metabolism.

BACKGROUND: Nandrolone is one of the most abused anabolic steroids, and its use in doping is increasing, as revealed by numerous positive cases during recent years in various sports. Different authors have reported the possible natural production of nandrolone metabolites in humans, and some of these authors argued that exhaustive exercise could increase nandrolone production in the body or induce dehydration and consequently lead to an increase of nandrolone metabolites in urine. METHODS: Volunteers (n = 22) ingested two 25-mg doses of [(13)C]nandrolone at 24-h intervals and collected urine specimens for 5 days. The labeled nandrolone metabolites 19-norandrosterone and 19-noretiocholanolone were identified and quantified by gas chromatography-mass spectrometry. RESULTS: Interindividual variability was observed in nandrolone excretion patterns and kinetics, as well as for the noretiocholanolone:norandrosterone ratio. The amounts of nandrolone metabolites measured at the excretion peak varied between 1180 and 38 661 microg/L for norandrosterone and 576 and 12 328 microg/L for noretiocholanolone. At the end of the excretion period, the noretiocholanolone:norandrosterone ratio was sometimes >1. The analysis of numerous spot-urine samples allowed the determination of an acceptable correlation between urinary creatinine and specific gravity for placebo- and steroid-treated individuals: y = 0.0052ln(x) + 1.0178 (r(2) = 0.8142) and y = 0.0068ln(x) + 1.0172 (r(2) = 0.7730), respectively. CONCLUSIONS: The excretion kinetics and patterns of labeled nandrolone show interindividual variability. More investigations are currently underway to estimate the influence of exhaustive exercises on excretion of labeled nandrolone metabolites in urine.

Adult↗

Development and validation of a capillary zone electrophoresis method for the determination of ephedrine and related compounds in urine without extraction.

A capillary zone electrophoresis (CZE) method, with UV detection and in the presence of dimethyl-beta-CD, was optimized by means of an experimental design for the separation and the simultaneous quantitation of ephedrine, pseudoephedrine, norephedrine (phenylpropanolamine) and norpseudoephedrine (cathine) in urine without any extraction. In this application, the optimization of the analytical conditions with an experimental design was preferred to a univariate study. Therefore, a central composite design was used and the following factors were investigated and varied simultaneously: buffer concentration, buffer pH and dimethyl-beta-CD concentration. In order to evaluate the influence of each experimental parameter on the analytical separation, the resolutions between the four compounds, as well as the separation time and generated current were observed and established as responses of the experimental design. A model was obtained for each response by linear multiple regression of a second-degree mathematical expression. After acceptance of the mathematical models, the most favorable conditions were determined by maximizing the resolutions between the four compounds and by setting the other responses at threshold values. Successful results were obtained with a 260 mM Tris-phosphate buffer at pH 3.5 in the presence of 13.3 mM dimethyl-beta-CD at 25 degrees C and with an applied voltage of 30 kV. Under these optimized conditions, a baseline separation of the four compounds was achieved in less than 6 min. The method was validated in terms of precision, linearity, accuracy and successfully applied for the determination of these compounds in urine samples without any extraction as well as in nutritional supplements.

Chromatography, Gas↗

Determination of zaleplon and zolpidem by liquid chromatography-turbo-ionspray mass spectrometry: application to forensic cases.

Zolpidem and zaleplon are two short-acting hypnotic agents used in Europe and in the USA. An atmospheric pressure ionisation liquid chromatography-mass spectrometry (Sciex API 150 EX) method was developed for the determination of zolpidem and zaleplon in whole blood. After single-step liquid-liquid extraction, the hypnotics were separated by gradient-elution with an ammonium formate buffer/acetonitrile eluent on an Inertsil ODS-3 column. Methaqualone was used as internal standard. The recovery was higher than 70% for both hypnotics and the internal standard. The best fit for the calibration curve was achieved, between 1 and 250 ng/ml, with 1/x quadratic regression. Coefficients of intra- and inter-assay variation calculated at 5, 25 and 100 ng/ml were less than 10%. The method was successfully applied to forensic cases.

Acetamides↗

Suicide by injection of a veterinarian barbiturate euthanasia agent: report of a case and toxicological analysis.

The history and toxicological findings of a suicidal case involving injection of a veterinarian barbiturate euthanasia agent (Vetanarcol containing pentobarbital are presented. Blood pentobarbital concentrations compatible with drug overdose were determined. Almost identical levels were found in blood, cerebrospinal fluid (CSF) and vitreous humour (VH). The highest concentration was measured in the bile. The present case is compared with similar rare cases in the literature.

Drug Overdose↗

Fatal aortic injury during laparoscopy: report of two cases.

The authors report the cases of two young women who died of massive hemorrhage resulting from trocar aortic injuries during abdominal laparoscopy. In the first case, wherein the patient underwent laparoscopy for cecopexy, the forensic autopsy showed a through-and-through perforation of the abdominal aorta and of the ileum. The other woman, who had morbid obesity, underwent a laparoscopy for gastroplasty. In this second case, the main postmortem findings were stab wounds of the thoracic aorta and of the diaphragm.

Adult↗

Childhood homicide: a 1990-2000 retrospective study at the Institute of Legal Medicine in Lausanne, Switzerland.

The authors retrospectively reviewed all homicides of children under 15 years of age referred to the Institute of Legal Medicine in Lausanne from January 1990 to December 2000. We report on 41 cases during this eleven-year period. Among those, 17 newborns and 24 older children, a higher proportion of males was found. Regarding newborn homicides, when the identity of the mother was known she was always identified as the perpetrator. With non-newborn homicides, the majority of the victims were killed at home and knew the offender. Two common profiles of these homicides could be determined. In the first scenario, one of the parents shot all the children and committed suicide afterwards. The second profile is defined as 'fatal child abuse' and concerned younger victims whose cause of death was the result of a cranio-cerebral trauma from battering or shaken baby syndrome.

Child Abuse↗

Effects of exercise on the secondary blood markers commonly used to suspect erythropoietin doping.

Numerous trials have reported that some haematological and biochemical parameters could be put together and be used to detect and fight recombinant erythropoietin doping. Unfortunately, none of the studies mentioned the necessity of taking pre-analytical precautions to avoid possible suspicious results coming from major plasma volume changes caused notably by dehydration. Therefore we studied the behaviour of the most common secondary blood markers before and after a strenuous physical activity to find out how reliable these parameters were. The soluble transferrin receptor and the haemoglobin concentrations as well as the haematocrit level increased significantly after effort, whereas the plasma EPO concentration and the reticulocyte count remained constant. On the other hand, if the values were corrected for haemoconcentration, the soluble transferrin receptor concentration remained stable.

Adult↗

Evaluation of a simplified method of the conduction system analysis in 110 forensic cases.

A simplified method of the His bundle analysis is evaluated by the study of 110 forensic cases. The atrioventricular node or its part were observed in 96 cases (87.3%), penetrating bundle in 92 cases (83.6%), branching and left bundles branch in 109 cases (99.1%) and right bundle branch in 73 cases (66.4%). The changes such as fibrosis and fatty infiltration show statistically significant differences (P<0.01) between progressive age groups confirming their degenerative and age-related nature. The study included as well nine cases of sudden unexpected death and two cases of sudden infant death syndrome (SIDS), for which the autopsy with histological examination and toxicological analysis resulted negative. For nine of these cases, pathological lesions were found which can even explain the fatal issue. Moreover, in the cases with known cause of death, potentially lethal changes were noticed. This simple, low cost technique could be proposed to forensic pathologists as easy to fit into the routine processing of autopsy material, allowing the detection of major abnormalities with minimal effort. The authors also consider the difficulties related to the interpretation of the pathological findings in the conduction system.

Adipose Tissue↗

[Medico-legal autopsy].

A medicolegal autopsy is a complex medical investigation which must be performed with precision and thoroughness by forensic pathologists who have gained experience in forensic procedures. Since 1999, due to the adoption by the Council of Europe of a recommendation in the harmonisation of medicolegal autopsy rules, forensic pathologists have a standardised protocol for autopsies. This recommendation specifies when and how autopsies should be carried out. This internationally accepted legal instrument is expected to ensure the credibility of medicolegal autopsy reports. Due to its importance as reference document, this protocol must be familiar to any physician dealing with legal medicine.

Autopsy↗

The human mandible in lateral view: elliptical fourier descriptors of the outline and their morphological analysis.

An original procedure based on new developments in elliptical Fourier methods associated with image analysis technics was applied to 117 human mandibles in lateral view (69 males, 48 females) in order to analyze interindividual variability and sexual dimorphism. Original parameters, called elliptical Fourier descriptors, allowed for the quantification of the shape of an outline irrespective of its morphological complexity, and provided a precise individual characterization. The use of step by step reconstructions with an increasing number of harmonics allowed for demonstration of the morphological contributions of the elliptical Fourier descriptors, and relationships to precise anatomical features were established. The first harmonics (1st to 8th) described the general mandibular shape, and the later harmonics (8th to 14th) characterized accessory and finer morphological features. The proportion of individuals presenting significant sexual dimorphism was 97.1% in males and 91.7% in females, and after size normalization 84.1% in males and 81.2% in females. Even after removal of the size component, these results in regard to mandibular dimorphism remained better than those found by classical approaches; this could be due to the use of elliptical Fourier analysis which takes into account all the information of the mandibular outline. Compared to the size component, the shape component seemed to be more important in the sexual dimorphism of the human mandible than previously recognized. The present approach opens interesting anthropological and clinical perspectives for the characterization of mandibular morphology.

Female↗

Post-mortem castration by a dog: a case report.

A man was found dead in a room where two dogs and a cat were wandering freely. His legs were bare and his underpants presented a few small tears. The deceased exhibited a partial emasculation but with only a small amount of bleeding. No other significant injuries were found, particularly no defence lesions. Death was natural, caused by the rupture of a myocardial infarct. A small piece of connective tissue was found in the gastric contents of one of the dogs. This fragment, as well as bloodstained hairs from its jaws, were analysed for DNA.

Animals↗

Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.

Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes. The present study used a double-blind crossover design to compare the effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on several skills required for safe driving. Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas chromatography-mass spectrometry-negative ion chemical ionization. Compared to smoking studies, relatively low concentrations were measured in blood. The highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL) 2.5-5.5 h after intake. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, (e.g., driving a friend to a party). Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction. Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the molar ratio of main active to inactive cannabinoids, greater than 10 was found to correlate with a strong feeling of intoxication. It also matched with a significant decrease in the willingness to drive, and it matched also with a significant impairment in tracking performances. The mathematic model II proposed by Huestis et al. (1992) provided at best a rough estimate of the time of oral administration with 27% of actual values being out of range of the 95% confidence interval. The sum of THC and 11-OH-THC blood concentrations provided a better estimate of impairment than THC alone. This controlled clinical study points out the negative influence on fitness to drive after medium or high dose oral THC or dronabinol.

Administration, Oral↗

Detection of exogenous GHB in blood by gas chromatography-combustion-isotope ratio mass spectrometry: implications in postmortem toxicology.

Because GHB (gamma-hydroxybutyrate) is present in both blood and urine of the general population, toxicologists must be able to discriminate between endogenous levels and a concentration resulting from exposure. In this paper, we propose a procedure for the detection of exogenous GHB in blood by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Following liquid-liquid and solid-phase extractions, GHB is derivatized to GHB di-TMS before analysis by GC-C-IRMS. Significant differences in the carbon isotopic ratio (delta(13)C-values > 13.5 per thousand) were found between endogenous and synthetic GHB. Indeed, for postmortem blood samples with different GHB concentrations (range: 13.8-86.3 mg/L), we have obtained GHB delta(13)C-values ranging from -20.6 to -24.7 per thousand, whereas delta(13)C-values for the GHB from police seizure were in the range -38.2 to -50.2 per thousand. In contrast to the use of cut-off concentrations for positive postmortem blood GHB concentrations, this method should provide an unambiguous indication of the drug origin.

Carbon Isotopes↗