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31.
Haiyung Cheng Jules I. Schwartz Charles Lin Raju D. Amin James R. Seibold Kenneth C. Lasseter David L. Ebel Dominick J. Tocco J. Douglas Rogers 《Biopharmaceutics & drug disposition》1994,15(5):409-418
MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD4-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg 14C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative. 相似文献
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Luis Hernandez-Garcia Gregory R Lee Alberto L Vazquez Chun-Yu Yip Douglas C Noll 《Magnetic resonance in medicine》2005,54(4):955-964
A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes. 相似文献
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Elsa Murray Ph.D. Estralita Martin Douglas Burton Leonard J. Deftos 《Journal of bone and mineral research》1989,4(6):831-838
Biochemical and molecular biological studies of osteoblastic cell function and hormonal regulation are frequently confounded by the inherent cellular heterogeneity and phenotypic instability of existing in vitro and in vivo model systems. A new technique (derived from Western blotting or antibody-based detection of protein molecules bound to nitrocellulose paper) is described for identification of individual cells which synthesize osteoblast-specific gene products (bone Gla-protein, type I collagen, and alkaline phosphatase) or produce cAMP in response to parathyroid hormone (PTH) or isoproterenol. Dispersed primary neonatal rat calvariae or osteogenic sarcoma cells were “plated” on Immobilon-P (a hydrophobic transfer membrane with very high protein-binding capacity) for 30 minutes to several hours, followed by agonist treatment, formalin fixation, hematoxylin staining, and immunostaining with a battery of antibodies specific for osteoblastic products. Individual cells and their secretory zones were visualized by light microscopy and counted. Treatment with PTH with or without isoproterenol resulted in increases in the percentages of osteoblastic cells elaborating cAMP, as well as the intensity of immunostaining, but had no effects on MCF-7 cells, a nonosteoblastic breast carcinoma control line. The percentage of cells within each primary osteoblastic cell population isolated or rat osteogenic sarcoma cell clone (G2 or C12) that elaborated bone-specific proteins or that generated cAMP in response to PTH varied with time and the individual cellular preparation, reconfirming the cellular heterogeneity of these systems. This method, in conjunction with techniques such as in vitro hybridization, should prove useful in characterizing discrete osteoblastic bone cell subpopulations and in clarifying mechanisms of hormonal regulation by local and systemic agents. 相似文献
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PURPOSE: To review the effects of the long QT syndrome (LQTS) in the parturient and the current anesthetic management of patients with LQTS. SOURCE: Relevant articles were obtained from a MEDLINE search spanning the years 1980-2006 and a PubMed search spanning the years 1949-2006. Bibliographies of retrieved articles were searched for additional articles. PRINCIPAL FINDINGS: The prevalence of LQTS in the developed world is one per 1,100 to 3,000 of the population. Clinically, LQTS is characterized by syncope, cardiac arrest and occasionally, by a history of seizures. The QT interval can also be prolonged by drugs, electrolyte imbalances, toxins and certain medical conditions. Long QT syndrome patients are at risk of torsades de pointes and ventricular fibrillation. Medical management aims to reduce dysrhythmia frequency. The LQTS is subdivided into different groups (LQT1-6) depending on the cardiac ion channel abnormality. Torsades can be precipitated by adrenergic stimuli such as stress or pain (LQT1 and 2), sudden noises (LQT2) or whilst sleeping (LQT3). Patients with LQTS require careful anesthetic management as they are at high risk of torsades perioperatively despite minimal data on the effects of anesthetic agents on the QT interval. While information on effects of LQTS in pregnancy is limited, the incidence of dysrhythmia increases postpartum. Isolated case reports of patients with LQTS women highlight several peripartum dysrhythmias. CONCLUSION: An understanding of LQTS and the associated risk factors contributing to dysrhythmias is important for anesthesthesiologists caring for parturients with LQTS. 相似文献
40.
Aims and Objectives The significance of beaten copper appearance (BCA) on skull radiographs in children following surgery for isolated sagittal
craniosynostosis has not been studied. This study was designed to look for any correlation between BCA and symptoms suggestive
of intracranial hypertension in this group of patients.
Materials and Methods Forty-eight consecutive children, who were operated for isolated sagittal synostosis from1987 to 2000 and had postoperative
skull radiographs, were included. Patients were divided into: (a) BCA group (n = 20), consisting of children who had beaten copper appearance on skull radiographs at last follow up, and (b) Non-BCA group
(n = 28), consisting of children who did not have this finding. Records were reviewed to look for symptoms suggestive of intracranial
hypertension, such as headache, head banging, and irritability.
Results Median age at surgery was 4.8 months for BCA group and 4 months for the non-BCA group. Follow up ranged from 4 to 156 months
with a mean of 36.2 months. Total of 28.6% (n = 6) of the children with follow up radiographs done at ≤18 months of age had BCA. The incidence of BCA increased to 83.3%
in children with skull radiographs performed after 48 months of age. In 18 (90%) children, the BCA was ‘diffuse’ with 5 (25%)
children having the maximum possible score of 8. In the BCA group, 45% (n = 9) had symptoms compared to 10.7% (n = 3) in the control group (p = 0.0068).
Conclusions This study suggests a significant number of children with BCA on radiographs develop symptoms suggestive of raised ICP following
surgical treatment in infancy and prolonged follow up may be warranted in this group of patients. 相似文献