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Biomedical subjects

N Sadeg

Publications and source records attributed to N Sadeg.

At least 19 recordsLinked to original sources
PubMed2003

[Utility of BNP measurement in the emergency room in patients with suspected unstable angina with a normal ECG].

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.

Angina, Unstable↗
PubMed2002

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.

Atrial Fibrillation↗
PubMed2002

[Serial determination of crimidine by HPLC/SE/SM in a patient ingesting a "mouse trap"].

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.

Chromatography, High Pressure Liquid↗
PubMed2002

[Anaphylactic shock and myocytic necrosis after treatment with 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.

Aged↗
PubMed2001

[Citalopram and Torsades de Pointes. A case report].

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.

Antidepressive Agents, Second-Generation↗
PubMed1997

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.

Analgesics, Opioid↗
PubMed1997

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.

Chromatography, High Pressure Liquid↗
PubMed1996

Rapid, specific and sensitive method for isoniazid determination in serum.

An original simple, specific and rapid high-performance liquid chromatographic assay for the determination of isoniazid (INH) in human serum is presented. The drug was extracted from the serum by protein precipitation with 30% (w/v) trichloroacetic acid, then the drug was reacted with the coupling reagent, trans-cinnamaldehyde, to form a derivative absorbing at 340 nm. A 20-microliters aliquot was injected into the chromatograph after neutralization with 1 M KOH solution. A liquid chromatograph equipped with a reversed-phase 30-microns C18 precolumn linked to a 4-microns C18 analytical column was used. The drug was eluted with a mixture of acetonitrile-water-triethylamine-acetic acid (400:600:2:1, v/v), pH value was 5 +/- 1. Flow-rate and wavelength were set at 1 ml/min and 340 nm, respectively. The extraction recoveries from human serum averaged 100% for INH at concentrations of 1, 2 and 4 mg/l. The coefficients of variation for three different concentrations for INH in serum in the within-day study varied between 1.2 and 3.5%, whereas those in the day-to-day study varied between 2.8 and 4.3%.

Antitubercular Agents↗
PubMed1995

In vitro metabolism of cyclosporin A with rabbit renal or hepatic microsomes: analysis by HPLC-FPIA and HPLC-MS.

Cyclosporin A (CsA) is in vivo mainly metabolized by hepatic cytochrome P450 IIIA to more than 21 metabolites, the major ones known as: M1, M17 and M21. The aim of this work is to explore the in vitro metabolism of CsA after incubation, in the presence of NADPH, with renal or hepatic microsomes obtained from rabbits pretreated with rifampycin (enzyme inducer) or erythromycin (enzyme inhibitor). The presumed metabolites were separated by semi-preparative high-performance liquid chromatography (HPLC) and identified in each collected fraction by fluorescence polarization immunoassay (FPIA) (HPLC-FPIA) using a non-specific polyclonal antibody. They were also analyzed by HPLC-mass spectrometry (MS) using fast atom bombardment (HPLC-MS-FAB). Five collected fractions gave positive results with FPIA. The major metabolites found were M1, M17 and M21 after identification by HPLC-MS-FAB and comparison with three corresponding standard metabolites. The CsA biotransformation rates were calculated by the amount of unmetabolized CsA and were linear with time. These mean rates (Vm) for 12-min incubation by renal microsomes of rabbits treated with rifampicin or erythromycin or untreated (control) were 0.11, 0.02 and 0.04 nmol/min x mg microsomal protein, respectively. These rates were 15-, 37-, and 30-fold lower than those obtained with hepatic microsomes of rabbits treated identically. As CsA metabolites are less cytotoxic than the parent drug, this weak renal biotransformation of CsA after in vitro incubation should be one of the mechanisms of its in vivo nephrotoxicity.

Animals↗
PubMed1994

In vitro comparative study on nephrotoxicity of cyclosporine A, its metabolites M1, M17, M21, and its analogues cyclosporines C and D in suspensions of rabbit renal cortical cells.

The potential nephrotoxicity of cyclosporine A (CsA), its three main metabolites: M1, M17 and M21, and its two analogues: cyclosporines C and D (CsC, CsD) was evaluated in vitro in suspensions of freshly isolated rabbit renal proximal tubular cells. This assessment involved the measure of enzyme release in the incubation media and the determination of Na+/K(+)-ATPase activity and glutathione content directly in the tubular cells. In vitro nephrotoxicity results of the six compounds tested could be respectively schematized as: CsA > CsD > CsC > M21 > M17, M1 It would be interesting to promote the study of promising CsC because of its low nephrotoxicity and its high immunosuppressive potency as previously reported.

Animals↗
PubMed1993

Effect of cyclosporin A and its metabolites and analogs on lipid peroxidation in rabbit renal microsomes.

Rabbit renal microsomes were used to investigate the effect on lipid peroxidation (LPO) of cyclosporin A (CsA) and its first generation metabolites M1, M17 and M21, and of two natural CsA analogs: cyclosporins C and D (CsC & CsD respectively), at concentrations of 1 to 10 micrograms/ml. No induction of lipid peroxidation was observed with these substances except CsA at a high level (10 microgram/ml); but at a concentration of CsA that would be reached in vivo, no inductive effect on LPO was noted. A moderate inhibitory effect upon LPO was observed with CsC and M21, but its biological significance is questionable.

Animals↗
PubMed1989

[Study of blood cyclosporine after kidney or bone marrow transplantation. Comparison of immunofluorescence and radioimmunoassay].

The apparition of cyclosporine, immunodepressive drug, has largely improved the organ transplantations. However, the range of blood concentrations must be defined to allow the efficacity of cyclosporine therapy and to avoid toxic reactions, because there are very important variations for a same dosage according to the individuals and the diseases. Relative to the low concentrations to be determined (about one hundred ng/ml), the most useful methods for cyclosporine measurement are based on immunochemical assays. This work compare the two methods: radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) simultaneously performed on several hundred samples. A very significant correlation exists between the two techniques (r = 0,80). The advantages of immunofluorescent assay consists in rapidity, sensibility and facility to realize emergency analysis.

Bone Marrow Transplantation↗
PubMedDate not supplied

Micro method for liquid chromatographic determination of cyclosporin A in whole blood with use of a rapid extraction procedure.

In this precise, reversed-phase liquid chromatographic procedure, Cyclosporin A (Cy A) is extracted from 300 microL of whole blood with cyclosporin D as internal standard by liquid-liquid extraction. A 20-microL aliquot of the extract, injected onto a Nucleosil octyl analytical column heated at 72 degrees C, is eluted with a mixture of acetonitrile and 0.01 M phosphate buffer, pH 5.5 at a flow rate of 1 mL/min. Detection is set at 210 nm. The chromatography is complete within 10 min. The detection limit is 25 micrograms/L. Between-run CVs range from 2.3 to 6.2% and recovery is 92.1 +/- 6.3%. The major advantages of our extraction procedure are the rapid clean-up method and the small volume required. This procedure is especially suitable for cyclosporine determination in pediatric transplantations.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

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.

Acute Disease↗
PubMedDate not supplied

In vitro and in vivo comparative studies on immunosuppressive properties of cyclosporines A, C, D and metabolites M1, M17 and M21.

Cyclosporine A (CsA) and its major metabolites: M1, M17 and M21 and two analogues: cyclosporines C (CsC) and D (CsD), were studied for their capacity to interfere with different in vitro activation pathways. Their inhibition potentials against the reaction of Graft-versus-Host (GvH) were also studied. The results showed: CsA, CsC and metabolite M17 were the most active compounds upon the inhibition of lymphocyte proliferation induced by different mitogens (ConA, PHA, PWM) and also on the proliferation of mixed lymphocyte cultures (MLC). The same results were observed concerning the direct activation by protein kinase C using a combined action of phorbol ester + calcium ionophore. In vivo using local GvH reaction, CsA and CsC proved more active than M17 in the two different combinations: H-2d --> (H-2b x H-2d)F1 and H-2k --> (H-2b x H-2k)F1 CsD and two metabolites M1 and M21 showed no or weak immunosuppressive effects. Overall, the immunosuppressive potency of six compounds could be schematized as: CsA > or = CsC > M17 > M1 > or = CsD > M21.

Animals↗