Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.
Serial CRP levels are useful in the diagnostic evaluation of neonates with suspected infection. Two CRP levels <1 mg/dL obtained 24 hours apart, 8 to 48 hours after presentation, indicate that bacterial infection is unlikely. The sensitivity of a normal CRP at the initial evaluation is not sufficient to justify withholding antibiotic therapy. The positive predictive value of elevated CRP levels is low, especially for culture-proven early-onset infections.
As long as an umbilical artery catheter is available for blood sampling with an in-line blood gas and chemistry monitor, significant reductions in neonatal RBC transfusions can be achieved. The patients most likely to benefit from monitor use are the smallest, most critically ill newborns.
Fetal and neonatal inflammation is associated with several morbidities of prematurity. Its relationship to retinopathy of prematurity (ROP) has not been investigated. Our objective was to determine the relationship between cytokine levels and ROP in the first 3 postnatal wks. Data for this study were derived from the NICHD Cytokine Study. Dried blood spots (DBS) were obtained from infants Ͻ1000 g on days 0 -1, 3 Ϯ 1, 7 Ϯ 2, 14 Ϯ 3, and 21 Ϯ 3. Infants were classified into three groups-no, mild, and severe ROP. Multiplex Luminex assay was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated using mixed-effects models after controlling for covariates. Of 1074 infants enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was associated with several clinical characteristics on unadjusted analyses. Eight cytokines remained significantly different across ROP groups in adjusted analyses. IL-6 and IL-17 showed significant effects in early time periods (D0 -3); TGF-, brain-derived neurotrophic factor (BDNF), and regulated on activation, normal T cell expressed and secreted (RANTES) in later time periods (D7-21) and IL-18, C-reactive protein (CRP), and neurotrophin-4 (NT-4) in both early and later time periods. We conclude that perinatal inflammation may be involved in the pathogenesis of ROP. (Pediatr Res 67: 394-400, 2010) R etinopathy of prematurity (ROP), a vasoproliferative disorder of the developing retina, is a major cause of blindness in infancy. ROP is a biphasic disease consisting of an initial phase of blunted vascular growth followed by a second phase of vasoproliferation that is recognized on ophthalmoscopy 4 to 6 wks after birth. Angiogenesis, the fundamental process involved in retinal vascular development, is tightly regulated by a complex network of cytokines, extracellular matrix components, and growth factors the action of which varies in a time-dependent fashion. Although inflammatory cytokines have the ability to modulate angiogenesis, their role in triggering the dysregulated angiogenesis in ROP has not been investigated (1). Abbreviations: BDNF, brain-derived neurotrophic factor; CRP, C-reactive protein; FIRS, fetal inflammatory response syndrome; GM-CSF, granulocyte-macrophage colony-stimulating factor; IVH, intraventricular hemorrhage; MCP-1, monocyte chemoattractant protein-1; MIP-1␣, macrophage inflammatory protein-1␣; MMP-9, matrix metalloproteinase-9; NEC, necrotizing enterocolitis; NT-4, neurotrophin-4; PVL, periventricular leukomalacia; RANTES, regulated upon activation, normal T cell expressed and secreted; ROP, retinopathy of prematurity; sIL-6R, soluble IL-6 receptor 0031-3998/10/6704-0394 PEDIATRIC RESEARCH
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