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OBJECTIVE: Fluindione is a vitamin K antagonist with a long half-life. This study was designed to investigate the pharmacokinetics and pharmacodynamics of multiple doses of fluindione in patients. METHODS: In a learning group of 49 patients who began fluindione treatment, blood samples were taken 12, 18, or 24 hours after one, three, and five doses. Concentration of fluindione, activity of clotting factors II, VII, IX and X, prothrombin complex activity (PCA), and international normalized ratio (INR) were measured. An indirect-response pharmacodynamic model was used for each effect. A comprehensive analysis was performed with a nonparametric population approach. The model was evaluated in 24 other patients: blood samples were taken 24 hours after two, three, four, and six doses; and PCA and INR were observed. RESULTS: Analysis of concentrations and clotting factor activities showed notably that (1) fluindione has a long half-life (median, 69 hours), and (2) concentration that inhibits the synthesis of the clotting factors by 50% varied for each factor, with a median ranging from 0.25 to 2.05 mg.L-1 for factors VII and II, respectively. The results obtained for INR and PCA were validated in the 24 subsequent patients. CONCLUSION: The population approach allowed the comparison of several pharmacodynamic submodels. This first application of the indirect-response model to multiple oral anticoagulant doses in patients confirmed that both the pharmacokinetics and the pharmacodynamics of fluindione show substantial interindividual variability. 相似文献
994.
Biodemographic trajectories of longevity 总被引:2,自引:0,他引:2
JW Vaupel JR Carey K Christensen TE Johnson AI Yashin NV Holm IA Iachine V Kannisto AA Khazaeli P Liedo VD Longo Y Zeng KG Manton JW Curtsinger 《Canadian Metallurgical Quarterly》1998,280(5365):855-860
Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives. 相似文献
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The history of studies of the great gerbil range was analyzed and position of the range boundaries was made more precise on the basis of the published data, museum collections, various natural maps, and authors' field observations. A scheme of the range regionalization is presented, in which three regional complexes of autonomous population groups are distinguished: Djungarian, Central Gobi, and East Gobi-Alashan'. Five autonomous population groups have also been isolated, which are located to the north of the main range: Shargin Gobi (?), Beger-nur, Orok-nur, Bulgan, and Bayan-dov. Regions with most favorable conditions for the great gerbil colonies were also shown. 相似文献
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998.
AA Nascimento RG Amaral JC Bizario RE Larson EM Espreafico 《Canadian Metallurgical Quarterly》1997,8(10):1971-1988
The discovery that the dilute gene encodes a class V myosin led to the hypothesis that this molecular motor is involved in melanosome transport and/or dendrite outgrowth in mammalian melanocytes. The present studies were undertaken to gain insight into the subcellular distribution of myosin-V in the melanoma cell line B16-F10, which is wild-type for the dilute gene. Immunofluorescence studies showed some degree of superimposed labeling of myosin-V with melanosomes that predominated at the cell periphery. A subcellular fraction highly enriched in melanosomes was also enriched in myosin-V based on Western blot analysis. Immunoelectron microscopy showed myosin-V labeling associated with melanosomes and other organelles. The stimulation of B16 cells with the alpha-melanocyte-stimulating hormone led to a significant increase in myosin-V expression. This is the first evidence that a cAMP signaling pathway might regulate the dilute gene expression. Immunofluorescence also showed an intense labeling of myosin-V independent of melanosomes that was observed within the dendrites and at the perinuclear region. Although the results presented herein are consistent with the hypothesis that myosin-V might act as a motor for melanosome translocation, they also suggest a broader cytoplasmic function for myosin-V, acting on other types of organelles or in cytoskeletal dynamics. 相似文献
999.
EE Schott SW Fitzgerald WJ McCarthy AA Nemcek AH Sonin 《Canadian Metallurgical Quarterly》1997,169(1):59-61
A case of intramuscular hemangioma (large vessel type) occurring in an eighteen year old woman is described. Medical history reported a pulled muscle in the same region 5 years earlier. By needle biopsy was performed the diagnosis of hematoma evolved to sclerosis. Since pain persisted the neoplasia was removed. Intramuscular hemangioma is a benign neoplasia. Recurrences are always due to incomplete excision. Angiosarcomas and liposarcomas are the two tumors to be differentiated from hemangiomas of skeletal muscle. The relative paucity of cases combined with widespread histological pictures make the diagnosis very difficult. 相似文献
1000.