Emory University

About: Emory University is a education organization based out in Atlanta, Georgia, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 51959 authors who have published 122469 publications receiving 6010698 citations.

Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure

Abstract: Time for primary review 26 days. Soon after the discovery of EDRF (endothelium derived relaxins factor) it became apparent that certain diseases are associated with an impairment of endothelium dependent vasorelaxation. In hypercholesterolemic rabbits and monkeys, vasorelaxation to acetylcholine is almost absent (Fig. 1) or changed into vasoconstriction [1,2]. Similar observations have been made in patients with coronary artery disease [3,4] or risk factors predisposing to atherosclerosis [5]. Likewise, endothelium-dependent vasorelaxation is abnormal in disease states such as heart failure, diabetes and hypertension [6]. In almost all of these disorders, there is a loss of endothelial production and/or bioavailability of NO (nitric oxide, nitrogen monoxide). This alteration of vascular function has been termed ‘endothelial dysfunction’ in the scientific literature. Although this term is widely used, it is quite imprecise. ‘Endothelial dysfunction’ may refer to impairments of important endothelial functions other than vasodilation, including anticoagulant and anti-inflammatory properties of the endothelium [7,8]. Nevertheless, ‘endothelial dysfunction’ has become widely used, and in fact, loss of nitric oxide in these conditions may contribute to alterations of other aspects of vascular function. The mechanisms underlying altered endothelium-dependent vascular relaxation in various disease states are almost certainly multifactorial, and seem to be dependent on the specific pathological condition, its duration, and the vascular bed being studied. Treatment with l-arginine or tetrahydrobiopterin has improved NO-mediated vasodilation in some instances, suggesting that there may be a deficiency of either the substrate for the enzyme NO synthase or one of its critical co-factors. Alterations of endothelial cell signaling may impair appropriate activation of the NO synthase in response to neurohumoral or mechanical stimuli. In very advanced atherosclerosis, expression of NO synthase in the endothelium declines, almost certainly reducing endothelium-dependent vascular relaxation. Finally, there is substantial evidence that in certain disease conditions, NO production … * Corresponding author. Tel.: +1-404-727-3710; fax: +1-404-727-3585 dharr02{at}emory.edu

Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants.

Abstract: OBJECTIVES. Our objectives were to identify factors associated with the duration of the first antibiotic course initiated in the first 3 postnatal days and to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis or death in extremely low birth weight infants with sterile initial postnatal culture results. METHODS. We conducted a retrospective cohort analysis of extremely low birth weight infants admitted to tertiary centers in 1998–2001. We defined initial empirical antibiotic treatment duration as continuous days of antibiotic therapy started in the first 3 postnatal days with sterile culture results. We used descriptive statistics to characterize center practice, bivariate analyses to identify factors associated with prolonged empirical antibiotic therapy (≥5 days), and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent necrotizing enterocolitis or death. RESULTS. Of 5693 extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5 days, received initial empirical antibiotic treatment, and had sterile initial culture results through the first 3 postnatal days. The median therapy duration was 5 days (range: 1–36 days); 2147 infants (53%) received prolonged empirical therapy (center range: 27%–85%). Infants who received prolonged therapy were less mature, had lower Apgar scores, and were more likely to be black. In multivariate analyses adjusted for these factors and center, prolonged therapy was associated with increased odds of necrotizing enterocolitis or death and of death. Each empirical treatment day was associated with increased odds of death, necrotizing enterocolitis, and the composite measure of necrotizing enterocolitis or death. CONCLUSION. Prolonged initial empirical antibiotic therapy may be associated with increased risk of necrotizing enterocolitis or death and should be used with caution.