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Jean-Pierre Goullé

Publications and source records attributed to Jean-Pierre Goullé.

7 recordsLinked to original sources

[Toxicological analysis at the beginning of the third millennium: promising new applications and future implications].

Enormous progress has been made in clinical toxicology over the last two decades, notably in the detection of pollutants. Chromatographic techniques have now replaced colorimetric reactions, which were non specific and poorly sensitive. Mass spectrometry has largely supplanted immunological methods, and is now coupled to gas phase (GC-MS or GC-MS/MS), liquid phase (LC-MS or LC-MS/MS) or induced coupled plasma spectrometry (ICP-MS). Few substances responsible for clinical syndromes now escape detection, be they medicinal drugs, plant products, pesticides, drugs of abuse, drugs used for criminal purposes, metals, metalloids, or poisons. Forensic medicine has benefited from these advances, notably in the fields of post-mortem toxicology, driving under the influence of drugs of abuse, and drug-facilitated crime. Rapid advances are being made in occupational and environmental monitoring of new substances with poorly documented toxicity. The French National Health and Environment Program, launched on 9 August 2004, specifically takes this problem into account. The author presents recent personal laboratory results illustrating the potential of these new techniques.

Environmental Monitoring↗

Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values.

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 Santé Publique du Québec (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.

Aged↗

Drug-facilitated robbery or sexual assault: problems associated with amnesia.

Amnesia following sedative-hypnotic drug exposure is discussed. Anterograde amnesia clearly occurs with many benzodiazepines. Several drugs are assessed: benzodiazepines and two hypnotics in particular that are structurally unrelated to the benzodiazepines but share some of their properties: zolpidem and zopiclone. The amnesic effects of these drugs are described, memory process, biology of memory, and memory process impairment documented. With these drugs anterograde amnesia has been demonstrated to be dose dependent. This effect is associated with hypnotic drugs, however, the receptors are different. As regards forensic medicine, a significant and specific type of amnesia should be considered: amnesia automatism or amnesic complex automatism. Also, several cases observed in our laboratory are presented to demonstrate the impact of amnesia.

Amnesia↗

Glycated hemoglobin: a useful post-mortem reference marker in determining diabetes.

Glycated hemoglobin (HbA(1c)) has been demonstrated to be a useful marker for long-term glucose control in diabetes. This parameter characterizes each non-enzymatic fixation of glucose on hemoglobin. It is a useful test in addition to periodic glycemia controls since it reflects the mean glycemia of the past 60 days. We studied the conservation of HbA(1c) at 4 degrees C as a function of time with different anti-coagulants and preservatives (3, 6 months, 1 year). A total of 106 tests were performed using the high performance liquid chromatography (HPLC) method dedicated to the semi-automatic analysis of HbA(1c) (Bio-Rad) and we applied the method in forensic cases. Conservation at 4 degrees C was good for as long as 3 months in blood samples collected with fluoride and 6 months in samples collected in a dry or in a heparinized tube. In non-diabetic subjects, HbA(1c) reference values obtained from forensic samples were identical to those of living controls (3.5-6.25% of total hemoglobin). All positive HbA(1c) results were confirmed by a medical evaluation. This method was successfully applied to five forensic cases. In cases of increased acetonemia, acetone or isopropanol are easily measured. However, in some unexplained post-mortem circumstances, increased HbA(1c) permits to differentiate alcoholic or starvation ketoacidosis from the diabetic cases. Glycated hemoglobin should, therefore, be considered the forensic marker of choice in the post-mortem diagnosis of a diabetic disorder and demonstrates its usefulness in post-mortem validation.

Adult↗

Determination of glycols in biological specimens by gas chromatography-mass spectrometry.

A simple extraction and derivatization procedure for the analysis of eight glycols (ethylene glycol, EG; diethylene glycol, DEG; triethylene glycol, TEG; 1,2-propanediol, 1,2-PD; 1,3-propanediol, 1,3-PD; 1,2-butanediol, 1,2-BD; 2,3-butanediol, 2,3-BD; and hexylene glycol, HXG) using a 2-microL serum or blood sample is described. Following deproteinisation with acetonitrile, derivatization to its mono or di TMS derivative, glycols were detected using gas chromatography-electron impact mass spectrometry equipped with a split-spitless inlet and a DB-5MS column in the scan mode from 40 to 500 amu. Gamma-hydroxybutyrate-d6 (GHB-d6) was used as the internal standard. The limits of detection and quantitation in 2 pL of serum ranged, respectively, from 0.7 mg/L for EG to 8.5 mg/L for TEG and from 1.3 mg/L for EG to 18.2 mg/L for 1,2-PD. A linear response was observed over the concentration range from 1 to 800 mg/L for EG and 18 from 800 for TEG and 1,2-PD for serum and blood. Coefficients of variation for both intra-assay precision and interassay reproductibility ranged respectively between 1.9% for TEG to 4.9% for 1,2-PD (11.8% for HXG) and 3.5% for DEG to 9% for 2,3-BD (20.4 for HXG) at the 400 mg/L serum level. The method was applied to plasma and whole blood.

Calibration↗