[Monitoring of adipocyte responsiveness by in situ microdialysis in lipodystrophy tissue: adjustment of a glycerol quantification method in small samples]. / [In Process Citation]

In situ microdialysis allows monitoring of metabolic cellular processes at the tissue level in vivo. In the assessment of physiopathologic alterations seen in lipodystrophy, monitoring of glycerol release is pivotal. Indeed, it allows to quantify the pharmacological responsiveness of subcutaneous adipose tissue in humans. Until now, the small volume of microdialysate collected (5-15 microL/sample) restricted the assessment of glycerol level to the use of the radio-enzymatic method or the reference spectrophotometric microanalysis technique. The aim of this study was to adapt the method of glycerol measurement by iminequinone spectrophotometry colorimetric assay (520 nm) using the following reagent: 0.5 IU Glycerokinase, 1.23 IU glycerophosphate oxidase, 0.98 IU peroxidase, 4.6 mM Mg, 5.4 mM 4-chlorophenol, 0.25 mM 4-aminoantipyrine and 1.4 mM ATP. The assay was setup to run on Olympus AU 2700 automate (15 pL sample volume). The sensitivity of the method was improved by adding a 0.2 mmol triglyceride (TG) solution and 1.5 IU lipase to samples, reducing the limit of free glycerol quantification to 0.020 mmol/L. The analytical repeatability was 2.0% and the reproducibility was 7.9%. The present method thus demonstrated the feasibility of pharmacodynamic exploration of local cutaneous responsiveness in vivo in clinical trials.

[BNP and dyspnea: proposition of a diagnostic strategy based on two cut-off]. / BNP et dyspnée: proposition d'une stratégie diagnostique basée sur deux seuils décisionnels de BNP.

The purpose of this study was to evaluate the cut-off value of brain natriuretic peptide (BNP) assayed with AxSYM BNP assay (Abbott). 86 patients have been included (mean age of 66 years). The clinical sensibility was 100% at 100 ng/L versus 80% at 250 ng/L. The clinical specificity was 66% at 100 ng/L versus 92% at 250 ng/L. The positive predictive value was 80% at 100 ng/L versus 92% at 250 ng/L. The negative predictive value was 100% at 100 ng/L versus 88% at 250 ng/L. The double cut-off strategy is more suitable to diagnose a dyspnea of cardiac origin than the usual strategy based on a single cut-off.value. With such a strategy, the two cut-off strategy improve the diagnosis of 9% in the total population.

[Proposal for a discriminant level of BNP in very elderly persons with heart failure]. / Proposition d'un seuil de BNP discriminant dans la population très âgée présentant une insuffisance cardiaque.

A diagnosis of heart failure (HF) in elderly patient can be difficult. The purpose of this study is to evaluate the cut-off of brain natriuretic peptide (BNP) Triage Assay (Biosite) in the diagnosis of HF in this population : 250 very older patients with age

[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.

[Utility of BNP measurement in the emergency room in patients with suspected unstable angina with a normal ECG]. / Utilité du dosage du BNP aux urgences chez les patients suspects d'angor instable avec ECG normal. A propos de 120 patients.

Unstable angina is a serious condition, difficult to diagnose in the emergency room. Clinical, electrocardiographic and biological signs (increased troponine) are not sensitive. The authors set out to assess whether measuring B natiuretic peptide in the emergency room was more sensitive for identifying symptomatic coronary lesions. One hundred and twenty patients admitted to the emergency room for chest pain compatible with the diagnosis of unstable angina and a normal ECG were included in this prospective study. All patients underwent coronary angiography during their hospital admission. The sensitivities of troponine at a threshold of 0.4 ng/ml and of brain natiuretic peptide (BNP) at a threshold of 10 pg/ml in this population were 66% and 92% respectively. The use of troponine and BNP together provided better results than troponine and BNP alone for the identification of patients with chest pain with significant coronary lesions.

Short-term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study.

It is well known that atrial fibrillation can lead to heart failure, and is attributed to rapid ventricular rate (tachycardia-induced cardiomyopathy). Some recent studies suggest the possible existence of an intrinsic left-ventricular factor related to atrial fibrillation, irrespective of other elements. In order to demonstrate the implication of this factor, we measured B-type Natriuretic Peptide, known as a functional marker of left-ventricular dysfunction, in 40 consecutive patients with chronic non-valvular atrial fibrillation, with low ventricular rate and absence of clinical heart failure or echocardiographic left-ventricular dysfunction. In all patients, Brain Natriuretic Peptide (BNP) plasma level was high and dramatically decreased 24 h after external electrical cardioversion (61.4 pg/ml before cardioversion, 23.5 pg/ml 1 day after cardioversion, P<0.002). Our study demonstrates that atrial fibrillation, in absence of high ventricular rate, induces an asymptomatic cardiac alteration that is not detectable by echocardiography.

[Serial determination of crimidine by HPLC/SE/SM in a patient ingesting a "mouse trap"]. / Détermination sérique de la crimidine par CLHP/ES/SM chez un patient ayant ingere un "souricide foudroyant".

Crimidine (2 chloro, 4 methyl, 6 dimethyl amidopyrine) is a synthetic rodenticide which causes acute poisonings after oral ingestion in human. Major toxic effects are consciousness disorders, hypertonic coma and convulsions. Toxic level in human is about 5 mg/Kg. An intoxication case is reported. Five serums collected at different times were analyzed with HPLC/ES/MS. Crimidine was extracted with ethylacetate with recovery over 80%. Linearity was up to 800 micrograms/L. LOQ and LOD were 0.5 and 0.3 microgram/L respectively. The coefficients of variation were less than 10% for repeatability and reproductibility. Serum levels varied from 368 micrograms/L for H0 to 64 micrograms/L for H10 and elimination of crimidine was linear in time.

Determination serique de la crimidine par clhp/es/sm chez un patient ayant ingere un « souricide foudroyant ¼.

Crimidine (2 chloro, 4 methyl, 6 dimethyl amidopyrine) is a synthetic rodenticide which causes acute poisonings after oral ingestion in human. Major toxic effects are consciousness disorders, hypertonic coma and convulsions. Toxic level in human is about 5 mg/Kg. An intoxication case is reported. Five serums collected at different times were analyzed with HPLC/ ES/MS. Crimidine was extracted with ethylacetate with recovery over 80 %. Linearity was up to 800 µg/L. LOQ and LOD were 0.5 and 0.3 µg/L respectively. The coefficients of variation were less than 10 % for repeatability and reproductibility. Serum levels varied from 368 µg/L for H0 to 64 µg/L for H10 and elimination of crimidine was linear in time.

[Anaphylactic shock and myocytic necrosis after treatment with Artotec]. / Réaction anaphylactique et nécrose myocytaire consécutives à la prise d'Artotec.

Treatment with non-steroid anti-inflammatory drugs associated with a prostaglandin analogue is common, but the potential cardiovascular effects are largely unknown. The authors report a case of myocardial necrosis and anaphylactic shock due to treatment with diclofenac and misoprostol. The reintroduction of the treatment in hospital led to the recurrence of the initial cutaneous and cardiac symptoms in this patient.

[Citalopram and Torsades de Pointes. A case report]. / Citalopram et torsades de pointes. A propos d'un cas.

Inhibitors of serotonin uptake are drugs prescribed without recognised cardiovascular risk. The authors report a case of torsades de pointes following Citalopram ingestion. In this patient, the proof of reintroduction in a hospital environment resulted in prolongation of the QT interval. Screening of patients for acquired or congenital long QT intervals is therefore necessary before starting treatment with Citalopram.

1H NMR spectroscopic investigation of serum and urine in a case of acute tetrahydrofuran poisoning.

This article reports the investigation by 1H nuclear magnetic resonance (1H NMR) spectroscopy of biological fluids in a case of intentional poisoning with tetrahydrofuran (THF). Occupational exposures to this solvent are well documented, but acute poisoning cases are extremely rare, and the one presented here is the second known case of this kind. Urine and serum samples were collected. Without any pretreatment, the presence of THF was confirmed by characteristic resonances at 1.90 and 3.76 ppm; high lactate levels were also observed. The presence of gamma-hydroxybutyric acid (GHB) was noted. Quantitative analysis was performed by relative integration of peak areas. THF concentrations were 813 and 850 mg/L (11.3 and 11.8 mmol/L), and GHB concentrations 239 and 2,977 mg/L (2.3 and 28.6 mmol/L) in serum and urine, respectively. A gas chromatographic-mass spectrometric method confirmed 1H NMR observations. The origin of GHB detected in serum and urine is also discussed.

Enantioselective high-performance liquid chromatography determination of methadone enantiomers and its major metabolite in human biological fluids using a new derivatized cyclodextrin-bonded phase.

The simultaneous determination of methadone (Mtd) enantiomers and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in human urine and serum by enantioselective HPLC using a new Cyclobond 1-2000 RSP column is described. After alkaline extraction from urine or serum with estazolam as an internal standard, Mtd enantiomers and its metabolite (EDDP) are separated on the previous column with reversed-mobile phase and detected at 210 nm. Peak resolutions are about 2.0 for Mtd enantiomers. The relative standard deviations (R.S.D.) of Mtd and EDDP standards are between 0.5 and 4.5%. Most drugs of abuse are shown not to interfere with this technique. The method has been applied to study the levels of each Mtd enantiomer and of its racemic metabolite in urine and serum of patients under maintenance treatment for opiate dependence. In urine, R-(-)-Mtd levels are always higher (about 2+/-0.5-fold) than those of S-(+)-Mtd and in most cases, metabolite concentrations are greater than those of global Mtd enantiomers. However, the R-(-) enantiomer levels of residual drug in serum of some patients were lower than those of its antipode. This method is suitable for pharmacokinetic and toxicological studies of Mtd enantiomers and its major metabolite in biological fluids.

Automated liquid-chromatographic analyzer used for toxicology screening in a general hospital: 12 months' experience.

We evaluated the clinical utility of an automated HPLC system (Remedi, Bio-Rad) for identification of drugs and metabolites in biological fluids. Serum or urine or both from 354 consecutive cases of poisoning were analyzed by the system and by a set of fluorescence polarization immunoassay (FPIA, Abbott) and thin-layer chromatographic (TLC) procedures. Antidepressants and most phenothiazines were recognized by the new system. Comparison of Remedi results with final clinical diagnoses yielded diagnostic specificity and sensitivity of 80% and 90%, respectively. Remedi detected 26 additional compounds that were neither reactive in the immunoassay screening tests nor detected by TLC procedures. Because the Remedi expands the range of drugs covered by the immunoassays and provides a rapid, preliminary report in emergency situations, we conclude that this system can be a useful complementary technique in the clinical toxicology laboratory. Although urine toxicological screening seemed adequate for a good toxicological report, blood analysis allows extra toxicokinetic data such as blood concentrations and half-life estimations.