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1.
Pharmacoepidemiol Drug Saf ; 17(4): 345-53, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18271060

ABSTRACT

PURPOSE: To determine the validity of pregnancy variables recorded in administrative databases of Quebec using patient medical charts as the gold standard among asthmatic pregnant women. METHODS: Three administrative databases were linked and provided information on maternal, pregnancy and infant characteristics for 726 pregnant asthmatic women who delivered in 1990-2000. Algorithms were developed to measure variables that were not recorded directly in the databases or to minimize the number of missing values for variables recorded in two or more databases. Medical file data were collected by two trained research nurses in 43 hospitals. The validity of categorical variables was assessed with sensitivity, specificity, predictive positive values (PPVs) and predictive negative values (PNVs), whereas the validity of continuous variables was assessed with Pearson correlation using the medical chart as the gold standard. RESULTS: The sensitivity of the sex of the baby, previous live birth and previous pregnancy ranged from 0.97 to 0.99. Corresponding figures were 0.92-0.98 for specificity. We also found high correlation coefficients, ranging from 0.875 to 0.999 for the length of gestation, dates of last menstruation and delivery, maternal age and birth weight. CONCLUSION: Pregnancy-related variables recorded in administrative databases or derived from algorithms based on two or more databases were found to be highly valid as compared to the medical chart among asthmatic women.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Databases, Factual/statistics & numerical data , Pregnancy Complications/drug therapy , Pregnancy Outcome , Adolescent , Adult , Algorithms , Anti-Asthmatic Agents/pharmacology , Cohort Studies , Databases, Factual/standards , Female , Humans , Infant, Newborn , Male , Medical Records , Pregnancy , Quebec , Sensitivity and Specificity
2.
J Pharmacol Exp Ther ; 311(3): 1121-30, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15277582

ABSTRACT

The kinin B1 receptor (B1R) has attracted interest as a potential therapeutic target because this inducible G protein-coupled receptor is involved in sustained inflammation and inflammatory pain production. Compound 11 (2-[(2R)-1-[(3,4-dichlorophenyl) sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl]-N-[2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl]acetamide) is a high-affinity nonpeptide antagonist for the human B1R, but it is potent at the rabbit B1R as well: its Ki value for the inhibition of [3H]Lys-des-Arg9-BK (bradykinin) binding to a novel myc-labeled rabbit B1R expressed in COS-1 is 22 pM. In contractility tests (organ bath pharmacology), we found that compound 11 is an apparently surmountable antagonist of des-Arg9-BK- or Lys-des-Arg9-BK-induced contraction of the rabbit isolated aorta (pA2 values of 10.6+/-0.14 and 10.4+/-0.12, respectively). It did not influence contractions induced by angiotensin II in the rabbit aorta or by BK or histamine in the jugular vein, but it suppressed the prostaglandin-mediated relaxant effect of des-Arg9-BK on the rabbit isolated mesenteric artery. Compound 11 (1 nM) inhibited both the phosphorylation of the extracellular signal-regulated kinase1/2 mitogen-activated protein kinases induced by Lys-des-Arg9-BK in serum-starved rabbit aortic smooth muscle cells and the agonist-induced translocation of the fusion protein B1R-yellow fluorescent protein expressed in human embryonic kidney (HEK) 293 cells. Compound 11 does not importantly modify the expression of myc-B1R over 24 h in HEK 293 cells (no detectable action as "pharmacological chaperone"). The present results support that compound 11 is a potent and highly selective antagonist suitable for further investigations of the role of the kinin B1R in models of inflammation, pain, and sepsis based on the rabbit.


Subject(s)
Bradykinin B1 Receptor Antagonists , Quinoxalines/pharmacology , Sulfones/pharmacology , Animals , Aorta, Thoracic/cytology , Aorta, Thoracic/drug effects , Blotting, Western , COS Cells , Cell Line , Chlorocebus aethiops , Epitopes/genetics , Genes, myc/genetics , Image Cytometry , In Vitro Techniques , Microscopy, Confocal , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Protein Folding , Rabbits , Receptor, Bradykinin B1/biosynthesis , Receptors, Cell Surface/biosynthesis , Receptors, G-Protein-Coupled/antagonists & inhibitors
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