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Medicine, Health Care and Philosophy - 相似文献
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Dr. Michael Gosland Pharm.D. Dr. Bert Lum Pharm.D. Dr. Julia Schimmelpfennig Pharm.D. Dr. James Baker Pharm.D. Dr Michael Doukas M.D. 《Pharmacotherapy》1996,16(1):16-39
Cisplatin in combination with other cytotoxic agents is the backbone for a potential cure of testicular germ cell neoplasms and is a critical factor in the substantial activity observed in the treatment of small cell lung cancer, bladder cancer, and ovarian germ cell tumors. Resistance to cisplatin at the onset of treatment or at relapse limits its curative potential, however. Laboratory studies using both cells selected for cisplatin resistance by exposure to sublethal concentrations and biopsy specimens from patients' tumors provide insights for the potential mechanisms of resistance. The mechanisms identified in vitro include a complex and wide array of related and unrelated pathways such as alterations in cellular drug transport, enhanced DNA repair dependent and independent of signal transduction pathways, and enhanced intracellular detoxification such as glutathione and metallothionein systems. Studies of these mechanisms have identified a number of agents with known potential for administration to humans and that reverse cisplatin resistance in vitro; for example, reversal of cellular accumulation defects by dipyridamole; inhibition of DNA repair by hydroxyurea, pentoxifylline, and novobiocin; inhibition of the glutathione system by ethacrynic acid and buthionine sulfoximine; and inhibition of signal transduction pathways by cyclosporine, tamoxifen, and calcium channel-blocking agents. Current phase I clinical trials are focusing on the most effective doses and schedules to administer these agents in combination with cisplatin. Initial uncontrolled trials in limited numbers of patients suggest that the addition of modulators of cisplatin has the potential to reverse resistance in patients previously failing therapy. Another promising avenue for circumventing cisplatin resistance is the development of noncross-resistant platinum analogs. 相似文献
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Susan W. Muir Katherine Berg Bert Chesworth Neil Klar Mark Speechley 《Journal of clinical epidemiology》2010,63(4):389-406
ObjectivesTo evaluate and summarize the evidence linking balance impairment as a risk factor for falls in community-dwelling older adults.Study Design and SettingSystematic review and meta-analysis. English language articles in MEDLINE, EMBASE, CINAHL (1988–2009), under keywords of accidental falls, aged, risk factors, and hip, radius, ulna, and humerus fractures; and bibliographies of retrieved articles. Community-dwelling older adults in a prospective study, at least 1-year duration, age more than 60 years, and samples not specific to a single disease-defined population were included. Sample size, inclusion/exclusion criteria, demographics, clinical balance measurement scale, type of fall outcome, method of fall ascertainment, length of follow-up, and odds ratio (OR) or risk ratio (RR) were extracted. Studies must have reported adjustment for confounders. Random effects meta-analysis to generate summary risk estimate was used. A priori evaluation of sources of heterogeneity was performed.ResultsTwenty-three studies met the selection criteria. A single summary measure could not be calculated because of the nonequivalence of the OR and RR, producing an overall fall risk of RR of 1.42 (1.08, 1.85) and OR of 1.98 (1.60, 2.46).ConclusionsBalance impairment imparts a moderate increase on fall risk in community-dwelling older adults. The type of fall outcome, the length of follow-up, and the balance measurement tool impact the magnitude of the association. Specific balance measurement scales were identified with associations for an increased fall risk, but further research is required to refine recommendations for their use in clinical practice. 相似文献
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Scarlett Lin Gomez Cynthia D O'Malley Antoinette Stroup Sarah J Shema William A Satariano 《BMC cancer》2007,7(1):193
Background
Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods. 相似文献8.
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Period, age, and cohort effects on substance use among young Americans: a decade of change, 1976-86 总被引:6,自引:4,他引:2 下载免费PDF全文
In an earlier article in this Journal, we reported analyses that differentiated among period, age, and cohort effects on substance use among American youth 18 to 24 years old, from the high school classes of 1976 to 1982 during the period of 1976 to 1982. The present analyses extend the classes and years to 1986, and the age range to 18-28. A cohort-sequential design is employed, based on annual surveys of nationally representative samples of high school seniors, plus annual follow-up surveys of each senior class. Twelve different classes of drugs, both licit and illicit, are examined. Several different types of period, age, and cohort effects over the last decade are identified. Alcohol use (monthly and occasions of heavy use), and the use of marijuana, cocaine, amphetamines, methaqualone, barbiturates, LSD, psychedelics other than LSD, and tranquilizers all showed period effects. Occasions of heavy drinking, cigarette smoking, monthly and daily use of alcohol, and annual prevalence of cocaine, amphetamines, barbiturates, LSD, and narcotics other than heroin showed age effects. Class effects were seen for cigarette smoking and daily marijuana use. 相似文献
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