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Article ; Online: Evaluation of the cardiovascular risk induced by cannabis use from a series of 43 autopsy cases.

Paul, Cotier / Charlotte, Mayer / Isabelle, Etting / de la Grandmaison Geoffroy, Lorin / Jean-Claude, Alvarez

2023 Volume 137, Issue 6, Page(s) 1725–1733

Abstract: The aim of this monocentric observational autopsy study was to confirm the existence of a link between cannabis use and cardiovascular risk. It was based on the analysis of autopsy findings, cardiovascular pathological findings, and toxicological data in ...

Abstract	The aim of this monocentric observational autopsy study was to confirm the existence of a link between cannabis use and cardiovascular risk. It was based on the analysis of autopsy findings, cardiovascular pathological findings, and toxicological data in 43 autopsy cases of people who died with tetrahydrocannabinol (THC) in their blood over a 2-year period. Hair analysis was performed when available (n = 40) to distinguish between occasional and chronic cannabis use and to take into account other possible exposures, including smoking, drug consumption, and the use of other drugs of abuse (mainly cocaine, heroin, and amphetamine). A statistically significant association (Fisher's exact test, p < 0.001) was found between cannabis use, an undetermined manner of death, and the presence of an arrhythmogenic cardiac condition. An association was also found between cannabis use and the presence of advanced coronary heart disease (p = 0.01), heart disease (including ischemic heart disease, p = 0.003), or cardiomyopathy (p = 0.01). Through its systemic vascular action, cannabis could be a factor in triggering sudden death in subjects with arrhythmogenic cardiac conditions. In view of this finding, the mode of death of subjects who died in the presence of THC in the blood would in most cases be an "accident." These results highlight the potential adverse cardiac effects associated with cannabis use.
Language	English
Publishing date	2023-08-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1055109-8
ISSN	1437-1596 ; 0937-9827
ISSN (online)	1437-1596
ISSN	0937-9827
DOI	10.1007/s00414-023-03079-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Population Pharmacokinetics of Hydroxychloroquine and 3 Metabolites in COVID-19 Patients and Pharmacokinetic/Pharmacodynamic Application

Jean Claude Alvarez / Benjamin Davido / Pierre Moine / Isabelle Etting / Djillali Annane / Islam Amine Larabi / Nicolas Simon

Pharmaceuticals, Vol 15, Iss 256, p

2022 Volume 256

Abstract: We develop a population pharmacokinetic model for hydroxychloroquine (HCQ) and three of its metabolites (desethylhydroxychloroquine, Des HCQ; desethylchloroquine, DesCQ; and didesethylchloroquine, didesCQ) in COVID-19 patients in order to determine ... ...

Abstract	We develop a population pharmacokinetic model for hydroxychloroquine (HCQ) and three of its metabolites (desethylhydroxychloroquine, Des HCQ; desethylchloroquine, DesCQ; and didesethylchloroquine, didesCQ) in COVID-19 patients in order to determine whether a pharmacokinetic (PK)/pharmacodynamic (PD) relationship was present. The population PK of HCQ was described using non-linear mixed effects modelling. The duration of hospitalization, the number of deaths, and poor clinical outcomes (death, transfer to ICU, or hospitalization ≥ 10 d) were evaluated as PD parameters. From 100 hospitalized patients (age = 60.7 ± 16 y), 333 BHCQ and M were available for analysis. The data for BHCQ were best described by a four-compartment model with a first-order input (KA) and a first-order output. For M, the better model of the data used one compartment for each metabolite with a first-order input from HCQ and a first-order output. The fraction of HCQ converted to the metabolites was 75%. A significant relationship was observed between the duration of hospitalization and BHCQ at 48 h (r 2 = 0.12; p = 0.0052) or 72 h (r 2 = 0.16; p = 0.0012). At 48 h or 72 h, 87% or 91% of patients vs. 63% or 62% had a duration < 25 d with a BHCQ higher or below 200 μg/L, respectively. Clinical outcome was significantly related to BHCQ at 48 h (good outcome 369 +/− 181 μg/L vs. poor 285 +/− 144 μg/L; p = 0.0441) but not at 72 h (407 +/− 207 μg/L vs. 311 +/− 174 μg/L; p = 0.0502). The number of deaths was not significantly different according to the trough concentration ( p = 0.972 and 0.836 for 48 h and 72 h, respectively).
Keywords	hydroxychloroquine ; desethylhydroxychloroquine ; desethylchloroquine ; didesethylchloroquine ; PK/PD ; COVID-19 ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	333
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transplacental transfer of glyburide in women with gestational diabetes and neonatal hypoglycemia risk.

Hanane Bouchghoul / Jean-Claude Alvarez / Céline Verstuyft / Jean Bouyer / Marie-Victoire Senat

PLoS ONE, Vol 15, Iss 5, p e

2020 Volume 0232002

Abstract: BACKGROUND:In pregnant women with gestational diabetes, glyburide can be an alternative to insulin despite concerns about its transplacental transfer. However, transplacental transfer of glyburide is poorly quantified and the relationship between cord ... ...

Abstract	BACKGROUND:In pregnant women with gestational diabetes, glyburide can be an alternative to insulin despite concerns about its transplacental transfer. However, transplacental transfer of glyburide is poorly quantified and the relationship between cord blood glyburide concentration and hypoglycemia has not been studied. Our objective was to quantify the transplacental transfer of glyburide at delivery and to study the association between the cord blood glyburide concentration and the risk of neonatal hypoglycemia in patients with gestational diabetes treated with glyburide. METHODS AND FINDINGS:INDAO was a multicenter, noninferiority, randomized trial conducted between May 2012 and November 2016 in 914 women with singleton pregnancies and gestational diabetes. An ancillary study was conducted in the 87 patients of the Bicêtre University Hospital Center. The sample consisted of 46 patients with utilizable assays at delivery. The relationships between glyburide concentration and the time since the last intake of glyburide and between fetal glyburide concentration and neonatal hypoglycemia were modeled with linear or logistic regressions using fractional polynomials. There was placental transfer of glyburide at a fetal to maternal ratio of 62% (95% CI [50; 74]). Umbilical cord blood glyburide concentration decreased steeply after the last maternal glyburide intake. After 24 hours, the mean umbilical cord blood concentration was less than 5 ng/mL. Neonatal hypoglycemia risk was increased with an odds ratio of hypoglycemia equal to 3.70 [1.40-9.77] for each 10 ng/mL increase in the cord blood glyburide concentration. However, no newborns were admitted to the NICU because of clinical signs of hypoglycemia or for treatment of hypoglycemia. CONCLUSION:Considering that neonatal glyburide exposure may be limited by stopping treatment a sufficient time before labor, there may still be a place for glyburide in the management of gestational diabetes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: LC–MS/MS quantification of free and Fab-bound colchicine in plasma, urine and organs following colchicine administration and colchicine-specific Fab fragments treatment in Göttingen minipigs

Fabresse, Nicolas / Adrian Thompson / Jean-Claude Alvarez / Julien Allard / Marine Sardaby / Michael Eddleston / R. Eddie Clutton

Journal of chromatography. 2017 Aug. 15, v. 1060

2017

Abstract: Clinical evaluation of a colchicine specific antigen-binding fragment (Fab) in order to treat colchicine poisoning required the development of an accurate method allowing quantification of free and Fab-bound colchicine in plasma and urine, and free ... ...

Abstract	Clinical evaluation of a colchicine specific antigen-binding fragment (Fab) in order to treat colchicine poisoning required the development of an accurate method allowing quantification of free and Fab-bound colchicine in plasma and urine, and free colchicine in tissues, to measure colchicine redistribution after Fab administration. Three methods have been developed for this purpose, and validated in plasma, urine and liver: total colchicine was determined after denaturation of Fab by dilution in water and heating; free colchicine was separated from Fab-bound colchicine by filtration with 30KDa micro-filters; tissues were homogenized in a tissue mixer. Deuterated colchicine was used as internal standard. Samples were extracted by liquid–liquid extraction and analyzed with a LC–MS/MS. LOQ were 0.5ng/mL in plasma and urine for free and total colchicine and 5pg/mg in tissues. The methods were linear in the 0.5–100ng/mL range in plasma and urine, and 5–300pg/mg in tissues with determination coefficients>0.99. Precision and accuracy of QC samples presented a CV<9.4%. The methods require only 200μL of sample and allow a high throughput due to short analytical run (2min). These methods were successfully applied to a pig intoxicated with colchicine and treated with colchicine specific Fab fragments.
Keywords	chromatography ; clinical examination ; colchicine ; denaturation ; filtration ; liquid-liquid extraction ; liver ; miniature swine ; poisoning ; swine ; tissues ; urine
Language	English
Dates of publication	2017-0815
Size	p. 400-406.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	1570-0232
DOI	10.1016/j.jchromb.2017.06.034
Database	NAL-Catalogue (AGRICOLA)

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Article: Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon)

Scala, Christopher / Amélie Marsot / Jean-Claude Alvarez / Marie-Josée Limoges / Nicolas Simon / Yann Locatelli

Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia Veterinary anaesthesia and analgesia. 2015 Mar., v. 42, no. 2

2015

Abstract: To assess the population pharmacokinetics of methadone in deer.Prospective non-randomized experimental trial.Twelve healthy adult sika deer (nine males and three females).Deer received intramuscular administration of racemic methadone hydrochloride at 0 ... ...

Abstract	To assess the population pharmacokinetics of methadone in deer.Prospective non-randomized experimental trial.Twelve healthy adult sika deer (nine males and three females).Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg−1 or 1 mg kg−1. Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM).A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour−1), metabolic clearance (34.6 L hour−1), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour−1), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour−1, 121.0 L hour −1, 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration.Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer.
Keywords	adults ; adverse effects ; Cervus nippon ; deer ; females ; half life ; intramuscular injection ; liquid chromatography ; males ; metabolites ; methadone ; models ; pharmacokinetics ; tandem mass spectrometry
Language	English
Dates of publication	2015-03
Size	p. 165-172.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2020582-X
ISSN	1467-2995 ; 1467-2987
ISSN (online)	1467-2995
ISSN	1467-2987
DOI	10.1111/vaa.12186
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Positive plasma cotinine during platinum-based chemotherapy is associated with poor response rate in advanced non-small cell lung cancer patients.

Philippine Dacosta-Noble / Adrien Costantini / Coraline Dumenil / Jennifer Dumoulin / Pierre Helly de Tauriers / Violaine Giraud / Sylvie Labrune / Jean-François Emile / Jean-Claude Alvarez / Thierry Chinet / Etienne Giroux Leprieur

PLoS ONE, Vol 14, Iss 7, p e

2019 Volume 0219080

Abstract: INTRODUCTION:Patients with advanced non-small cell lung cancer (NSCLC) are most of the time treated with a first-line cytotoxic chemotherapy. Tobacco use is responsible for 90% of lung cancer. The aim of this study was to evaluate the impact of smoking ... ...

Abstract	INTRODUCTION:Patients with advanced non-small cell lung cancer (NSCLC) are most of the time treated with a first-line cytotoxic chemotherapy. Tobacco use is responsible for 90% of lung cancer. The aim of this study was to evaluate the impact of smoking continuation during first-line chemotherapy on tumor response in advanced-stage NSCLC. MATERIALS AND METHODS:All patients with an advanced-stage NSCLC (IIIb or IV), treated with first-line platinum-based chemotherapy in our Department between June 2013 and July 2017 were included. Smoking status was assessed at inclusion by self-report, then at the tumor assessment consultation after 2 months of treatment, by both self-report and plasmatic cotinine measurement. Chemotherapy response, progression-free survival (PFS), overall survival (OS) and stage 3-4 toxicity were registered. RESULTS:Ninety-seven patients were included: 8 (8%) declared to be non-smokers, 56 (58%) current smokers and 33 (34%) former smokers at diagnosis. At the first tumor evaluation, 24 (25%) self-reported as active smokers and 73 (75%) as non-smokers; overall response rate (ORR) was respectively 38% and 48% (p = 0.373). Fifty-four patients had a plasmatic cotinine evaluation at the first tumor evaluation. Seventeen patients (32%) had a positive cotinine rate (median 108ng/mL, IQR 31-236). Six patients (35%) had positive cotinine rate whereas declaring to be non-smokers at the first tumor evaluation. ORR was 18% in case of positive cotinine rate, and 57% when negative (p = 0.007). Regardless of the method for smoking status evaluation, PFS, OS and grade 3-4 toxicities were similar between smoker and non-smoker patients at the first tumor evaluation. CONCLUSION:Smoking continuation during platinum-based chemotherapy, reflected by positive plasma cotinine rate, was associated with a poor ORR.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of screening for drugs of abuse and benzodiazepines in forensic blood samples using Evidence InvestigatorTM analyser

Stanislas Grassin Delyle / Bertille Mathieu / Emuri Abe / Jean-Claude Alvarez

Annales de Toxicologie Analytique, Vol 20, Iss 1, Pp 17-

2008 Volume 24

Abstract: Introduction: Semi-quantitative detection of 4 classes of drugs of abuse (opiates, cocaine, cannabinoids and amphetamines) and benzodiazepines in haemolysed whole blood by Evidence Investigator analyser has been evaluated in this study. 128 forensic ... ...

Abstract	Introduction: Semi-quantitative detection of 4 classes of drugs of abuse (opiates, cocaine, cannabinoids and amphetamines) and benzodiazepines in haemolysed whole blood by Evidence Investigator analyser has been evaluated in this study. 128 forensic blood samples known to be positive for at least one of these classes by chromatography coupled to mass spectrometric detection were analysed. Results and discussion: Specificity was 79.0% for amphetamines, 98.1% for cannabinoids, and 100% for opiates, cocaine, and benzodiazepines. Sensitivity was 33.3% for amphetamines, 78.4% for benzodiazepines, 93.2% for cannabinoids, 93.5% for opiates and 95.2% for cocaine. 3.9% of false negatives were observed all classes taken together, due to low concentrations of analytes or due to a bad recognition of some analytes by antibodies. The 4.0% of false positive results were predominantly observed during amphetamines detection, probably due to presence of biogen amines, as it has previously been reported. An improvement of the technique has been carried out by adding a supplementary wash step during sample preparation. An optimisation of cutoff levels is possible to reduce false negative results during benzodiazepines and cannabinoids detection. Conclusion: This immunoanalytical method enables an efficient detection of opiates, cocaine, cannabinoids and benzodiazepines in forensic blood samples. However a further confirmation and quantification by mass spectrometry techniques remains necessary.
Keywords	Drugs of abuse ; whole blood ; biochip ; immunoanalysis ; Toxicology. Poisons ; RA1190-1270 ; Public aspects of medicine ; RA1-1270 ; Medicine ; R ; DOAJ:Public Health ; DOAJ:Health Sciences
Language	French
Publishing date	2008-01-01T00:00:00Z
Publisher	EDP Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Survival time estimation using Injury Severity Score (ISS) in homicide cases

Forensic science international. 2013 Dec. 10, v. 233

2013

Abstract: The aim of our study was to assess the value of ISS to estimate survival time in a retrospective study of all homicidal deaths in the Western suburbs of Paris between 1994 and 2008. Stab wounds were the most common cause of death. Survival time between ... ...

Abstract	The aim of our study was to assess the value of ISS to estimate survival time in a retrospective study of all homicidal deaths in the Western suburbs of Paris between 1994 and 2008. Stab wounds were the most common cause of death. Survival time between assault and death, determined in 107 cases out of 511 homicide cases, ranged from 0min to 25 days (mean 39h). There was an overall significant association between the survival time and the ISS score. ISS and survival time were strongly associated with male victims and a clear trend was seen with women. Regarding the type of wounds, a trend was seen with gunshot wounds and blunt injuries, but not with stab wounds. There was no influence of blood toxicological results and resuscitation attempts. Overall, ISS was a good predictor of a survival under 30min.
Keywords	blood ; death ; forensic sciences ; males ; retrospective studies ; women ; France
Language	English
Dates of publication	2013-1210
Size	p. 99-103.
Publishing place	Elsevier Ireland Ltd
Document type	Article
ZDB-ID	424042-x
ISSN	1872-6283 ; 0379-0738
ISSN (online)	1872-6283
ISSN	0379-0738
DOI	10.1016/j.forsciint.2013.08.026
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An epidemic of dystonic reactions in central Africa

Nicolas Peyraud / Florentina Rafael / Lucy Anne Parker / Michel Quere / Gabriel Alcoba / Christian Korff / Michael Deats / Pernette Bourdillon Esteve / Jean-Clément Cabrol / Micaela Serafini / Iza Ciglenecki / Monica Rull / Islam Amine Larabi / Frédéric Baud / Francesco Grandesso / Benoit Kebela Ilunga / Jean-Claude Alvarez / Paul N Newton

The Lancet Global Health, Vol 5, Iss 2, Pp e137-e

2017 Volume 138

Keywords	Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2017-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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