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991.
BACKGROUND: The Asymptomatic Carotid Atherosclerosis Study (ACAS) showed that carotid endarterectomy was beneficial for symptom-free patients with carotid stenosis of 60% or more. This finding raises the question of whether widespread screening to identify cases of asymptomatic carotid stenosis should be implemented. OBJECTIVE: To determine whether a screening program to identify cases of asymptomatic carotid stenosis would be a cost-effective strategy for stroke prevention. DESIGN: Cost-effectiveness analysis using published data from clinical trials. SETTING: General population of asymptomatic 65-year-old men. INTERVENTION: Patients who were screened for carotid disease with duplex Doppler ultrasonography were compared with patients who were not screened. If ultrasonography found significant carotid stenosis (> or = 60%), disease was confirmed by angiography before carotid endarterectomy was done. MEASUREMENTS: Quality-adjusted life-years, costs, and marginal cost-effectiveness ratios. RESULTS: When the conditions and results of ACAS were modeled and it was assumed that the survival advantage produced by endarterectomy would last for 30 years, the lifetime marginal cost-effectiveness of screening relative to no screening was $120,000 per quality-adjusted life-year. Sensitivity analysis showed that marginal cost-effectiveness decreased to $50,000 or less per quality-adjusted life-year only under implausible conditions (for example, if a free screening instrument with perfect test characteristics was used or an asymptomatic population with a 40% prevalence of carotid stenosis was found). CONCLUSIONS: Surgery offers a real but modest absolute reduction in the rate of stroke at a substantial cost. A program to identify candidates for endarterectomy by screening asymptomatic populations for carotid stenosis costs more per quality-adjusted life-year than is usually considered acceptable.  相似文献   
992.
The ability of antiviral and antiretroviral drugs to enter the brain is a critical issue in the treatment of many viral brain diseases, including HIV-related neurologic disease. Much of the literature concerning nucleoside analog entry into the nervous system focuses on drug levels in the cerebrospinal fluid (CSF), equating these with drug levels in the brain extracellular fluid (ECF) as though the two compartments intermix freely. We review the anatomic and physiologic aspects of drug entry into CSF and into brain ECF, as well as the exchange processes between these two compartments. In most instances drug concentrations in the CSF and ECF compartments bear little relationship to one another and using CSF concentrations to extrapolate brain ECF concentrations may significantly overestimate the latter. Accepted terminology and methodology for making measurements of blood-brain barrier function are discussed. Studies of brain uptake that express results as brain:plasma ratios, or that have used microdialysis, may overestimate the amount of drug reaching the brain. Using published data, we present an estimate of the time course of Zidovudine (AZT) concentrations in brain ECF and show that brain concentrations of AZT will likely be below that necessary to inhibit HIV-1 replication when AZT is administered systemically. Antiviral nucleosides and oligonucleotides appear to have limited entry into the brain when given systemically, which may hinder therapy of viral brain diseases, while some of the protease inhibitors may enter the brain more readily. Alternative methods for increasing antiviral and antiretroviral drug delivery to brain are discussed.  相似文献   
993.
Anecdotal reports suggest cattle with fescue toxicosis may not respond to vaccination and thus, experience increased incidence of Bovine Respiratory Disease Complex (BRDC) when shipped to feedlots. Fescue toxicosis causes hypoprolactemia in cattle. Hypoprolactemia decreases humoral immune responses in mice. Therefore, a study was conducted to compare the magnitude of primary and secondary humoral immune responses against specific antigens in cattle grazing endophyte-infected or endophyte-free fescue. Angus steers were blocked by weight and allocated into four groups. Two groups grazed endophyte-infected (EI) fescue and the other two groups grazed endophyte-free (EF) fescue. All steers were injected IM on d 0 and 21 with lysozyme without adjuvant and concanavalin. A (Con A) with sheep red blood cells (SRBC) in incomplete adjuvant of Freund. Steers were bled on days 0, 21 and 35 post-vaccination. Average daily gains (ADG), alkaline phosphatase (ALP) activity, cholesterol concentrations, rectal temperatures, and serum prolactin concentrations were measured to confirm fescue toxicosis in steers grazing EI fescue. Antibodies to Con A and SRBC were determined by ELISA and hemagglutination assay, respectively. The ADG were decreased for the EI group during the first month. Rectal temperature were elevated and serum prolactin concentrations were decreased in the EI group. Cholesterol and ALP concentrations also were decreased in the EI group. Primary and secondary immune responses against Con A tended to be increased and were increased against SRBC in the EI group. Antibodies against lysozyme were not induced in either group. In conclusion, cattle grazing EI fescue mounted similar humoral immune responses to vaccination, despite hypoprolactemia, as cattle grazing EF fescue. Increases in bovine respiratory disease in cattle maintained on EI fescue probably is not associated with lack of humoral immune response to vaccination protocols as a result of fescue toxicosis.  相似文献   
994.
995.
Methodological aspects of the analysis of protective measures in agriculture in the long-term period of liquidation of the consequences of a nuclear accident are considered. Examples of the estimations of countermeasure effectiveness with the use of the cost-benefit analysis, as well as methods of the estimation of intervention levels and examples of a comparison of various protective measures with the use of several criteria of effectiveness are discussed.  相似文献   
996.
BACKGROUND: Intraoperative echocardiography is a valuable monitoring and diagnostic technology used in cardiac surgery. This reports our clinical study of the usefulness of intraoperative echocardiography to both surgeons and anesthesiologists for high-risk coronary artery bypass grafting. METHODS: From March to November 1995, 82 consecutive high-risk patients undergoing coronary artery bypass grafting were studied in a four-stage protocol to determine the efficacy of intraoperative echocardiography in management planning. Alterations in surgical and anesthetic/hemodynamic management initiated by intraoperative echocardiography findings were documented in addition to perioperative morbidity and mortality. RESULTS: Intraoperative echocardiography initiated at least one major surgical management alteration in 27 patients (33%) and at least one major anesthetic/hemodynamic change in 42 (51%). Mortality and the rate of myocardial infarction in this consecutive high-risk study population using intraoperative echocardiography and in a similar group of patients without the use of intraoperative echocardiography was 1.2% versus 3.8% (not significant) and 1.2% versus 3.5% (not significant), respectively. CONCLUSIONS: We conclude that when all of the isolated diagnostic and monitoring applications of perioperative echocardiography are routinely and systematically performed together, it is a safe and viable tool that significantly affects the decision-making process in the intraoperative care of high-risk patients undergoing primary isolated coronary artery bypass grafting and may contribute to the optimal care of these patients.  相似文献   
997.
The authors propose and test an exemplar-based random walk model for predicting response times in tasks of speeded, multidimensional perceptual classification. The model combines elements of R. M. Nosofsky's (1986) generalized context model of categorization and G. D. Logan's (1988) instance-based model of automaticity. In the model, exemplars race among one another to be retrieved from memory, with rates determined by their similarity to test items. The retrieved exemplars provide incremental information that enters into a random walk process for making classification decisions. The model predicts correctly effects of within- and between-categories similarity, individual-object familiarity, and extended practice on classification response times. It also builds bridges between the domains of categorization and automaticity.  相似文献   
998.
The molecular mechanisms which underlie the development of the olivocerebellar topography are not fully understood. Insulin-like growth factor-I (IGF-I) is a growth factor known to play important roles in neural development and it has been identified within the cerebellum and the inferior olive. To assess the contribution of IGF-I to the development of climbing fibre topography, the distribution of IGF-I-like immunoreactivity (IGF-I IR) was identified in the cerebellar cortex and inferior olive of rats, 0, 3, 5, 7, 10, 15, 21, 28 and 90 days old. In the cerebellar cortex, IGF-I IR was localised solely to Purkinje cells and its distribution was spatially and temporally regulated in a manner which coincides with climbing fibre development. At birth, weak IGF-I IR was detected in a few Purkinje cells in the ventral vermis. More Purkinje cells became positive until at postnatal day 7(P7) all Purkinje cells displayed IGF-I IR. Subsequently, a subpopulation of Purkinje cells lost their reactivity for IGF-I to leave IGF-I-positive cells organised into sagittal bands by P15. IGF-I IR was also seen in all subdivisions of the inferior olive between birth and P10 in a distribution which paralleled the maturation of the inferior olive. The Purkinje cell and inferior olivary IGF-I IR parallels climbing fibre development and thus the results of this study support the hypothesis that IGF-I is involved in the development of climbing fibre topography.  相似文献   
999.
1000.
To analyze the critical parameters for effective antiviral cytotoxic T lymphocyte (CTL) activity in vivo, control of lymphocytic choriomeningitis virus (LCMV) infection in the spleen was studied after adoptive transfer of different spleen cell populations into preinfected recipients. The quantitative, qualitative and kinetic requirements for virus control were defined and related to in vitro assays to compare the antiviral protective function of CTL from naive, acutely infected and memory mice. Treatment of mice with an established but limited LCMV infection by adoptive transfer of spleen cells from acutely LCMV-infected mice led to complete virus elimination mainly mediated by donor-derived CD8+ T cell-mediated, perforin-dependent cytotoxicity. Since virus is continuously spreading and the number of infected target cells rapidly increases, the time until target cell lysis is achieved was critical: if release of viral progeny was not prevented early, additional time to perform effector function did not improve overall virus control. When the function of various cell populations was compared in this model, we found that CTL from naive and memory mice perform considerably less well than CTL from acutely infected mice. In vitro studies indicated that this is probably due to the fact that they can not fulfill the limiting time requirements for immediate antiviral protection: while CTL from acutely infected mice can perform lytic effector function immediately, memory CTL require a considerable reactivation time before they can lyse infected target cells. This reactivation does not necessarily involve cell division. These findings illustrate how critical time limitations are for CTL to mediate early control of a dynamic virus infection in vivo.  相似文献   
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