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Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens. These barrier defense capacities become destructive during disease processes like necrotizing enterocolitis (NEC) when an otherwise maturationally normal, yet dysregulated and immature, immune defense system is associated with high levels of certain inflammatory mediators like TNFa. In Part II the authors discuss the rationale for why rhG-CSF has theoretical advantages in managing NEC or sepsis by augmenting neonatal neutrophil number, neutrophil expression of Fcg and complement receptors, as well as phagocytic function and oxidative burst. rhG-CSF also has potent anti-TNFa functions that may serve to limit extension of tissue destruction while not impairing bacterial killing capacity. Healthy, non-infected neutropenic and septic neonates differ in their ability to respond to rhG-CSF; however, no neonatal clinical trials to date have identified a clear clinical benefit of rhG-CSF therapy. This manuscript will review the literature and evidence available for identifying the ideal subject for cytokine treatment using NEC as the model disease target. [ABSTRACT FROM AUTHOR]

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens. These barrier defense capacities become destructive during disease processes like necrotizing enterocolitis (NEC) when an otherwise maturationally normal, yet dysregulated and immature, immune defense system is associated with high levels of certain inflammatory mediators like TNFa. In Part II, the authors will discuss the theoretical advantages of using rhG-CSF in managing NEC or sepsis by augmenting neonatal neutrophil number and killing capacity including an unexpected, paradoxical and potent anti-TNFa function that may serve to limit extension of tissue destruction without impairing bacterial killing capacity. The authors conclude by arguing that NEC may be the ideal disease process for testing whether a clearly defined clinical benefit of cytokine therapy can prove beneficial. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Extremely low birth weight (ELBW) infants often acquire catheter-related infections (CRIs) when a percutaneously inserted central catheter (PICC) is used for parenteral nutrition or drug administration. Our objective was to compare the incidence of CRIs after we established a 'PICC Maintenance Team' for the proactive management--compared to expectant management--of these lines. STUDY DESIGN: We did a prospective collection and analysis of catheter-related sepsis data over a 15-month period from February 1, 1998 through May 1, 1999. Eligible patients included all neonates weighing <1000 g at birth. RESULTS: There was a significantly decreased incidence of CRIs, to a rate of 7.1%, or 5.1/1000 catheter days (p<0.05). CONCLUSION: 'Proactive' management of PICC, significantly reduced the incidence of CRIs. The reduction in infection rate is estimated to save 180 hospitalized patient days/100 very low birth weight neonates, with a concomitant savings in morbidity and medical expense. [ABSTRACT FROM AUTHOR]