Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

卒中医疗体系之急诊医疗服务的实施策略:美国心脏协会/美国卒中协会急诊医疗服务体系专家组和卒中委员会的政策声明

尽管卒中的预防、诊断、治疗和康复已取得一些进展,但卒中在美国仍然是第三大死亡原因和长期残疾的主要原因.每年约有70万人新发或复发卒中[1].在过去10年里,急性卒中诊治的一些进展,包括纤溶和其他短期疗法的引入,突出显示了急诊医疗服务(emergency medical services,EMS)机构和急诊医疗服务体系(emergency medical services systems,EMSS)在优化卒中医疗中的关键作用[2-7].     

An ecocultural model predicts Neanderthal extinction through competition with modern humans

Archaeologists argue that the replacement of Neanderthals by modern humans was driven by interspecific competition due to a difference in culture level. To assess the cogency of this argument, we construct and analyze an interspecific cultural competition model based on the Lotka−Volterra model, which is widely used in ecology, but which incorporates the culture level of a species as a variable interacting with population size. We investigate the conditions under which a difference in culture level between cognitively equivalent species, or alternatively a difference in underlying learning ability, may produce competitive exclusion of a comparatively (although not absolutely) large local Neanderthal population by an initially smaller modern human population. We find, in particular, that this competitive exclusion is more likely to occur when population growth occurs on a shorter timescale than cultural change, or when the competition coefficients of the Lotka−Volterra model depend on the difference in the culture levels of the interacting species.Neanderthals are a human species (or subspecies) that went extinct, after making a small contribution to the modern human genome (1, 2). Hypotheses for the Neanderthal extinction and their replacement by modern humans, in particular as recorded in Europe, can be classified into those emphasizing competition with modern humans and those arguing that interspecific competition was of minor relevance. Among the latter are the climate change (3) and epidemic/endemic (4) hypotheses. However, an ecocultural niche modeling study has shown that Neanderthals and modern humans exploited similar niches in Europe (5), which, together with a recent reassessment of European Paleolithic chronology showing significant spatiotemporal overlap of the two species (6), suggests a major role for interspecific competition in the demise of the Neanderthals.Replacement of one species (or population) by another is ultimately a matter of numbers. One competing species survives while the other is reduced to, or approaches, zero in size. In the classical Lotka−Volterra model of interspecific competition, this process is called competitive exclusion (7). If Neanderthals were indeed outcompeted by modern humans, the question arises: Wherein lay the advantage to the latter species? Many suggestions have been made, including better tools (8), better clothing (9, 10), and better economic organization (11). These hypotheses share the premise that modern humans were culturally more advanced than the coeval Neanderthals.The purpose of our paper is threefold. First, we extend the Lotka−Volterra-type model of interspecific competition by incorporating the “culture level” of a species as a variable that interacts with population size (12, 13). Here, culture level may be interpreted as the number of cultural traits, toolkit size, toolkit sophistication, etc. Although, as noted above, many anthropological and archaeological discussions invoke interspecific cultural competition, there is, to the best of our knowledge, no mathematical theory of this ecocultural process. A mechanistic resource competition model is difficult to justify at present, because there is a limited understanding of “what the species are competing for… [or] how they compete” (14). Second, we use our interspecific cultural competition model to explore, analytically and numerically, the possibility that a difference in culture level, or in underlying learning ability, may produce competitive exclusion of a comparatively (although not absolutely) large regional (Neanderthal) population by an initially smaller (modern human) one. Third, we assume the competition coefficients of the Lotka−Volterra model to depend explicitly on the difference in the culture levels of the interacting species (rather than to be constants) and ask how this modification affects the invasion and subsequent dynamics.Dependence of the culture/technology level of a human population on its size has been the focus of many theoretical (15–21) as well as psychological (22–24), archaeological (25, 26), and ethnological (27–30) studies. However, the coupled dynamics of population size and culture level, where both quantities are treated as variables, has received less theoretical attention (12, 13, 31, 32).Taking refs. 12 and 13 as the point of departure, we extend previous treatments by introducing two such populations in direct competition with each other in the Lotka−Volterra framework. The two populations are described in terms of their size, N_i (≥0), their culture level z_i (≥0), i (=1, 2), and parameters to be defined below. We ask whether a population can be replaced by an initially smaller one, which has an advantage in culture level or in learning ability. This ecological perspective on the competition between “size−culture profiles” may inform ongoing debate on the replacement of Neanderthals by modern humans.     

Periods of differing mortality distribution during the first year after acute myocardial infarction

The mortality rate after acute myocardial infarction (AMI) has generally been modeled by a single exponential function. The present study was undertaken to determine, in 3 different populations, whether or not periods exist during the first year after AMI which have mortality distributions that differ from this pattern. The 3 patient populations included San Diego (346 patients, 71 deaths), Vancouver (704 patients, 146 deaths), and Copenhagen (1,140 patients, 262 deaths). Hospital admission was within 24 hours of the onset of symptoms, and patients dying within the first 24 hours after hospital admission or of noncardiac or unknown causes were not analyzed. The mortality between 2 and 21 days in the combined data base was 11.4% (range 10.9 to 11.7) and from 3 weeks to 1 year 10.5% (range 9.0 to 11.3). A high degree of similarity was noted among the shapes of the 3 survival curves. The hypothesis of an exponential mortality rate during the entire first year was rejected. Using a special statistic, changepoints at days 17,23, and 24 in the 3 populations (21 days for the combined data base) were identified and used thereafter to divide the year into 2 separate periods of mortality within which exponentiality for the mortality rate was not rejected. The point by which exactly 50% of deaths had occurred was day 19, with 75% of deaths occurring by day 100. These data further define the natural history after AMI and indicate optimal follow-up periods for short- and longer-term management strategies based on risk assessment or trials of risk reduction after AMI.