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Neutrophils are considered to be central to the pathogenesis of most forms of acute lung injury (ALI). For the sake of clarity, neutrophil involvement in ALI can be conceptualized as consisting of sequential stages, beginning with their sequestration in the pulmonary microvasculature, followed by adhesion and activation, and culminating in the production of a microbicidal or "effector" response, such as the generation of reactive oxygen species or release of proteolytic enzymes. Great strides have been made in elucidating these various stages of neutrophil involvement. Recent studies have focused on the intracellular signaling pathways that govern neutrophil activation and have elucidated complex cascades of kinases and other intracellular signaling molecules that allow for amplication of the neutrophil response, yet simultaneously confer specificity of a response. We believe that the inflammatory response in ALI may initially be adaptive, such as the pivotal role played by neutrophils in a bacterial or fungal infection. Ultimately, it is the persistence or the dysregulation of neutrophil activation that may lead to ALI. An increased understanding of how neutrophils function will facilitate the design of therapeutic strategies that retain the beneficial aspects of the inflammatory response, while avoiding unnecessary tissue damage.

A meta-analysis of prospective studies O R I G I N A L A R T I C L EOBJECTIVE -Women are at a much lower risk of coronary disease mortality than men are. It is widely believed that diabetes "erases" this female advantage, increasing the risk of heart disease much more in women than in men. In reality, the extent of this increased risk is controversial, with studies showing conflicting results and wide confidence intervals. Clarification of this issue has implications for the pathogenesis of coronary disease, and for public health efforts to reduce coronary disease in women.RESEARCH DESIGN AND METHODS -We performed a meta-analysis to calculate a summary estimate of the relative risk of coronary death among women with diabetes as compared to those without. For comparison, we also calculated the analogous risk among men. All prospective cohort studies containing both men and women, and both patients with and without diabetes, were examined. Sixteen studies were identified; 10 had sufficient data for statistical analysis.RESULTS -After combining studies that adjusted for other cardiac risk factors, the relative risk of coronary death from diabetes was 2.58 (95% CI 2.05-3.26) for women and 1.85 (1.47-2.33) for men. This difference is statistically significant (P = 0.045). Other sensitivity analyses did not change these estimates appreciably.CONCLUSIONS -The impact of diabetes on the risk of coronary death is significantly greater for women than men. Further research is required to explain this clinically meaningful difference between the sexes. Diabetes Care 23:962-968, 2000

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