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21.
Choc Miles G. Hsuan Francis Honigfeld Gilbert Robinson William T. Ereshefsky Larry Crismon Miles L. Saklad Stephen R. Hirschowitz Jack Wagner Richard 《Pharmaceutical research》1990,7(4):347-351
Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics. 相似文献
22.
Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk 总被引:5,自引:0,他引:5 下载免费PDF全文
P.J. Devereaux Lee Goldman Deborah J. Cook Ken Gilbert Kate Leslie Gordon H. Guyatt 《Canadian Medical Association journal》2005,173(6):627-634
THIS IS THE FIRST OF 2 ARTICLES EVALUATING cardiac events in patients undergoing noncardiac surgery. In this article, we review the magnitude of the problem, the pathophysiology of these events, approaches to risk assessment and communication of risk. The number of patients undergoing noncardiac surgery worldwide is growing, and annually 500 000 to 900 000 of these patients experience perioperative cardiac death, nonfatal myocardial infarction (MI) or nonfatal cardiac arrest. Although the evidence is limited, a substantial proportion of fatal perioperative MIs may not share the same pathophysiology as nonoperative MIs. A clearer understanding of the pathophysiology is needed to direct future research evaluating prophylactic, acute and long-term interventions. Researchers have developed tools to facilitate the estimation of perioperative cardiac risk. Studies suggest that the Lee index is the most accurate generic perioperative cardiac risk index. The limitations of the studies evaluating the ability of noninvasive cardiac tests to predict perioperative cardiac risk reveals considerable uncertainty as to the role of these popular tests. Similarly, there is uncertainty as to the predictive accuracy of the American College of Cardiology / American Heart Association algorithm for cardiac risk assessment. Patients are likely to benefit from improved estimation and communication of cardiac risk because the majority of noncardiac surgeries are elective and accurate risk estimation is important to allow informed patient and physician decision-making. 相似文献
23.
Chain transfer constants (Ctr) for three phosphonated thiols in methyl methacrylate (MMA) polymerization at 60°C were determined from measurements of the degree of polymerization. These thiols were: diethyl 2-mercaptoethyl phosphate ( 1 ), diethyl 2-mercaptoethylamidophosphate ( 2 ), and tetraethyl mercaptomethylethylene bis(phosphate) ( 3 ). Transfer efficiencies of the thiols were found to be dependent upon their structures. The Ctr value of thiol 2 with MMA was the lowest in the present series, which can be attributed to a possible charged tautomeric form which eventually may reduce the electron density on the thiol, thus rendering the chain transfer reaction with the PMMA radical less feasible. Ctr values of thiol 1 were evaluated at 55, 60, 65, 70 and 75°C. This thiol behaves as an “azeotropic” transfer agent for MMA at 96°C. 相似文献
24.
Mathieu Beaulieu David Williamson Gilbert Pichette Jean Lachaine 《Infection control and hospital epidemiology》2007,28(11):1305-1307
Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use. 相似文献
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Gilbert H. L. Tang Paul W. M. Fedak Terrence M. Yau Richard D. Weisel Alex Kulik Donald A. G. Mickle Ren-Ke Li 《European journal of cardio-thoracic surgery》2003,23(6):907-916
Current therapies for congestive heart failure are limited in efficacy or in applicability. Cardiac cell transplantation offers a novel therapeutic approach to improve heart function. Although significant progress has been made over the past decade in the development of cell transplantation, only recently have investigators studied the changes in ventricular function following cell transplantation. This review article describes the latest research developments, evaluates recent studies of ventricular function after cell transplantation, and discusses the future directions of cell transplantation as a new therapy to ‘repair broken hearts’. 相似文献
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28.
D Gilbert P Joly F Jouen A Thibout A Delpech E Thomine P Lauret F Tron 《Journal of autoimmunity》1992,5(2):173-182
The production of monoclonal autoantibodies derived from individuals with autoimmune diseases constitutes a powerful tool to analyse an autoimmune process at both the antigen and antibody levels. We established a human anti-epithelial cell surface monoclonal antibody by applying hybridoma technology using peripheral blood lymphocytes from a patient with pemphigus vulgaris using a heteromyeloma as the fusion partner. The F12 monoclonal antibody displays four major characteristics: (1) it belongs to the IgM, kappa class; (2) it binds to the cell surface of stratified squamous and simple epithelia; (3) it recognizes an antigenic determinant associated with the desmosomal complex as demonstrated by indirect immunoelectron microscopy; (4) by immunoblotting analysis, it reacts with a 185 kDa polypeptide which was also recognized by a few pemphigus vulgaris sera. Although the F12 monoclonal antibody does not have the immunochemical properties of classical pemphigus vulgaris autoantibodies, several arguments suggest its relevance to the pemphigus vulgaris autoimmune response and, therefore, the heterogeneity of the antigen/antibody systems involved in this autoimmune disorder. 相似文献
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30.
E A Mohide G W Torrance D L Streiner D M Pringle R Gilbert 《Journal of clinical epidemiology》1988,41(5):475-482
In the absence of a quality of life instrument which is applicable to the caregivers of elderly relatives and amenable to a cost-utility analyses, the Caregiver Quality of Life Instrument (CQLI) was developed using Torrance's time trade-off technique. The CQLI was administered to 30 family caregivers and 10 relatives of well elderly. Utility scores were obtained for three standardized caregiver situations and the subject's own state. The CQLI could be completed by almost all subjects. Good test-retest reliability was established. The subjects were able to discriminate between degrees of caregiver wellbeing using standardized states and the CQLI scores discriminated among groups of subjects. The CQLI detected within-subject change in caregivers whose relatives received institutional respite care. The CQLI appears to be feasible, reliable, valid, and responsive to change. Further CQLI applications and research are recommended. 相似文献