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Arch Dermatol 2002 Dec;138(12):1615-6
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PMID: 12472361, UI: 22360661
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Arch Dermatol 2002 Dec;138(12):1607-12
Blackburn Royal Infirmary, Blackburn, England.
PMID: 12472355, UI: 22360655
Forensic Sci Int 2002 Nov 5;130(1):34-43
Department of Legal Medicine, Division of Medical Intelligence and Informatics, Graduate School of Biomedicel Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. namera@hiroshima-u.ac.jp
A simple and rapid method for quantitation of tropane alkaloids in biological materials has been developed using an Extrelut column with gas chromatography-mass spectrometry (GC-MS). Biological materials (serum and urine) were mixed with a borate buffer and then applied to an Extrelut column. The adsorbed tropane alkaloids were eluted with dichloromethane before a GC-MS analysis. Atropine-d(3) was used as an internal standard. The extracted tropane alkaloids were converted to trimethylsilyl derivatives prior to GC analysis, to improve the instability of tropane alkaloids from heating and the property of them for a GC column. The recoveries of the compounds, which had been spiked to biological materials, were more than 80%. The GC separation of the derivatives from endogenous impurities was generally satisfactory with the use of a semi-polar capillary column. Tropane alkaloids showed excellent linearity in the range of 10-5000 ng/ml and the limit of detection was 5.0 ng/ml for biological materials. The present method is simple and more rapid than those previously reported, and was applied to a poisoning case. It is useful for the routine analysis of tropane alkaloids in cases of suspected tropane alkaloids poisoning.
PMID: 12427448, UI: 22315004
Forensic Sci Int 2002 Nov 5;130(1):25-8
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ikegaga-tky@umin.ac.jp
An 89-year-old male patient, hospitalized with Parkinson's syndrome, suddenly died shortly after an intravenous drug injection. The conditions indicated that an overdose of nicardipine (1.3 mg/(mlkg)) may be given to the patient. At the autopsy, no pathological changes were noted. With a capillary gas chromatograph with mass spectrometer (GC-MS), nicardipine (4.97 microg/ml) and its pyridine metabolite (M-5, 5.0 microg/ml) were detected in the heart blood of the deceased. This result indicated that an overdose of intravenous nicardipine caused a sudden death of a patient in a poor condition.
PMID: 12427446, UI: 22315002
Hum Exp Toxicol 2002 May;21(5):253-62
Drug Safety Evaluation, Pfizer Global Research and Development, Groton, Connecticut 06340, USA. amacher@groton.pfizer.com
Biological markers (biomarkers) are used to recognize, characterize and monitor treatment-related responses following exposure to xenobiotics. Biomarkers serve three primary applications in toxicology: 1) to confirm exposure to a deleterious agent, 2) to provide a system for monitoring individual susceptibility to a toxicant, and 3) to quantitatively assess deleterious effects of a toxicant to an organism or individual. Because the liver is a general target for adverse effects of drugs and other chemicals, biomarkers of untoward hepatic response to xenobiotics are of particular interest to the pharmaceutical toxicologist. General requirements for the latter category of biomarkers are sample availability, target organ specificity, sensitivity for the toxicity of interest, accessibility, a relatively short half-life, and available detection systems. Biomarkers that can be assayed in biological fluids from both human and animal subjects are particularly desirable. Histologically, acute and subacute hepatic toxicity commonly involves necrosis, steatosis, cholestasis, vascular disorders, or multiple lesions. The purpose of this review is to summarize reported applications using clinical analytes and biochemical indicators of hepatic dysfunction with emphasis on those that show promise of supplementing or improving upon standard laboratory procedures. Liver function markers refer to peripheral indicators of hepatic synthetic and secretory activities, enterohepatic function, or perturbations of the hepatic uptake and clearance of circulating biomolecules. Liver injury biomarkers include various peripheral proteins released in response to a cellular damage or locally, proteins that are significantly altered within the liver. These include both circulating cytosolic, mitochondrial, or canalicular membrane markers, and the up-regulation or depletion of radical scavengers, modulators, and stabilizers of intracellular damage. Subsequent recovery from a toxic insult involves repair, regenerative, and proliferative responses that constitute the third class of biomarkers. Of these, protein markers found either in sera, plasma, or urine either during or just prior to the early manifestation of histological hepatic lesions are of greatest interest. Examples of a number of these markers, their documented applications in humans or animals, and potential advantages as well as limitations are presented.
PMID: 12141396, UI: 22136479
Hum Exp Toxicol 2002 May;21(5):247-52
Department of Biochemistry, Ege University Faculty of Medicine, Izmir, Turkey.
Recently, interindividual variations in serum paraoxonase (PON1) activity and the differences in its metabolic activity towards different organophosphates (OPs) caused by the coding region polymorphisms L55M and Q192R have been found to be important risk factors in susceptibility to OP poisoning. In this study, we investigated the effect of PON1 on the outcome of acute OP intoxication and the effect of acute OP intoxication on PON1. Twenty-eight OP-poisoned patients and 66 healthy volunteers were studied. Patients were evaluated for the clinical manifestations of OP intoxication as well as PON1 activity, PON1 mass and PON1 polymorphisms. Butyrylcholine-esterase (BChE) activity was 50% lower (2,276 +/- 738 U/L versus 5,037 +/- 1,553 U/L, P<0.01) while PON1 activity was 30% lower [114.2 +/- 67.4 nmol/mL/min versus 152.9 +/- 78.9 nmol/mL/ min, P<0.05) in patients than in controls. We observed that the PON1 and BChE activities of eight of the original subjects returned to normal levels when they were reinvestigated six months after exposure. The frequency of the PON192Q allele was significantly higher in patients than controls (85.7% versus 59.7%, chi2=6.745, P=0.034). QQ/ MM individuals had the lowest activity towards paraoxon, while RR/LL individuals had the highest activity. Our data indicate that interindividual differences in PON1 activity and the PON1-55 and -192 polymorphisms are important risk factors in susceptibility to acute OP poisoning; therefore, identifying an individual's PON1 alloenzymes may play an important role in the treatment of patients suffering from OP intoxication.
PMID: 12141395, UI: 22136478
Int J Dermatol 2002 Sep;41(9):600-1
Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, FL, USA.
PMID: 12358833, UI: 22246590
Int J Dermatol 2002 Sep;41(9):533-49
Department of Dermatology, New York-Presbyterian Medical Center, New York, NY 10032, USA.
PMID: 12358821, UI: 22246578
JAMA 2003 Jan 1;289(1):36-7
PMID: 12515265, UI: 22403004
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N Engl J Med 2003 Jan 2;348(1):81-2; author reply 81-2
PMID: 12510051, UI: 22398316