Skip to main content Accessibility help
×
Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-18T18:56:31.944Z Has data issue: false hasContentIssue false

33 - Neonatal necrotizing enterocolitis: clinical observations and pathophysiology

Published online by Cambridge University Press:  10 December 2009

Patti J. Thureen
Affiliation:
University of Colorado at Denver and Health Sciences Center
Michael S. Caplan
Affiliation:
Department of Pediatrics, Evanston Northwestern Healthcare, Northwestern University, Feinberg School of Medicine, Evanston IL
Tamas Jilling
Affiliation:
Department of Pediatrics, Evanston Northwestern Healthcare, Northwestern University, Feinberg School of Medicine, Evanston IL
William W. Hay
Affiliation:
University of Colorado at Denver and Health Sciences Center
Get access

Summary

Establishment of appropriate enteral feedings in the premature infant is a frequent cause of concern in the neonatal intensive care unit due to the dreaded complication of neonatal necrotizing enterocolitis (NEC), an ischemic and inflammatory necrosis of bowel that results in significant mortality, longer lengths of stay, increased costs, and possibly increased risk for abnormal neurodevelopmental outcomes. The disease incidence varies between centers and across continents, but ranges between 3% and 28% with an average of approximately 8%–10% in infants born weighing less than 1500 g. Despite significant advances in neonatal care, the morbidity and mortality resulting from NEC has not improved over the last three decades, with recent reports of NEC mortality ranging between 10%–30%.

Clinical presentation

The disease presents clinically in premature neonates with variable symptoms of intestinal bleeding, emesis, abdominal distension, lethargy, and apnea and bradycardia, and signs of abdominal tenderness, thrombocytopenia, metabolic acidosis, tachycardia, respiratory failure, and, if severe, shock. The diagnosis is typically made by the identification of pneumatosis intestinalis (air in the bowel wall) on abdominal radiograph, although in some cases of NEC, commonly in un-fed patients, pneumatosis is not appreciated. In these situations, NEC may be diagnosed surgically or pathologically, or in some instances by ultrasound appreciation of portal venous air. Bell and colleagues suggested a classification scheme that differentiates feeding intolerance (stage I) from true NEC (stage II) and advanced NEC (stage III with peritonitis and/or perforation).

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Kliegman, R. M., Fanaroff, A. A.Necrotizing enterocolitis. N. Engl. J. Med. 1984;310:1093–103.CrossRefGoogle ScholarPubMed
Vohr, B. R., Wright, L. L., Dusick, A. M.et al.Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994. Pediatrics 2000;105:1216–26.CrossRefGoogle Scholar
Uauy, R. D., Fanaroff, A. A., Korones, S. B.et al.Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. J. Pediatr. 1991;119:630–8.CrossRefGoogle ScholarPubMed
Walsh, M. C., Kliegman, R. M.Necrotizing enterocolitis: treatment based on staging criteria. Pediatr. Clin. N. Am. 1986;33:179–201.CrossRefGoogle ScholarPubMed
Bell, M. J., Ternberg, J. L., Feigin, R. D.et al.Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg. 1978;187:1–7.CrossRefGoogle ScholarPubMed
Ballance, W. A., Dahms, B. B., Shenker, N., Kliegman, R. M.Pathology of neonatal necrotizing enterocolitis: a ten-year experience. J. Pediatr. 1990;117:S6–13.CrossRefGoogle ScholarPubMed
Brown, E. G., Sweet, A. Y.Preventing necrotizing enterocolitis in neonates. J. Am. Med. Assoc. 1978;240:2452–4.CrossRefGoogle ScholarPubMed
Dunn, L., Hulman, S., Weiner, J., Kliegman, R.Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial. J. Pediatr. 1988;112:622–9.CrossRefGoogle ScholarPubMed
Troche, B., Harvey-Wilkes, K., Engle, W. D.et al.Early minimal feedings promote growth in critically ill premature infants. Biol. Neonate 1995;67:172–81.CrossRefGoogle ScholarPubMed
Slagle, T. A., Gross, S. J.Effect of early low-volume enteral substrate on subsequent feeding tolerance in very low birth weight infants. J. Pediatr. 1988;113:526–31.CrossRefGoogle ScholarPubMed
Stoll, B. J., Kanto, W. P. Jr, Glass, R. I., Nahmias, A. J., Brann, A. W. Jr.Epidemiology of necrotizing enterocolitis: a case control study. J. Pediatr. 1980;96:447–51.Google ScholarPubMed
Kamitsuka, M. D., Horton, M. K., Williams, M. A.The incidence of necrotizing enterocolitis after introducing standardized feeding schedules for infants between 1250 and 2500 grams and less than 35 weeks of gestation. Pediatrics 2000;105:379–84.CrossRefGoogle ScholarPubMed
Tyson, J. E., Kennedy, K. A.Minimal enteral nutrition for promoting feeding tolerance and preventing morbidity in parenterally fed infants. Cochrane Database Syst Rev. 2000;CD001241.Google ScholarPubMed
Di Lorenzo, M., Bass, J., Krantis, A.An intraluminal model of necrotizing enterocolitis in the developing neonatal piglet. J. Pediatr. Surg. 1995;30:1138–42.CrossRefGoogle ScholarPubMed
Caplan, M. S., Hedlund, E., Adler, L., Hsueh, W.Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis. Pediatr. Pathol. 1994;14:1017–28.CrossRefGoogle Scholar
Lucas, A., Cole, T. J.Breast milk and neonatal necrotising enterocolitis [see comments]. Lancet 1990;336:1519–23.CrossRefGoogle ScholarPubMed
Caplan, M. S., Russell, T., Xiao, Y.et al.Effect of polyunsaturated fatty acid (polyunsaturated fatty acids) supplementation on intestinal inflammation and necrotizing enterocolitis (necrotizing enterocolitis) in a neonatal rat model. Pediatr. Res. 2001;49:647–52.CrossRefGoogle Scholar
Caplan, M. S., Lickerman, M., Adler, L., Dietsch, G. N., Yu, A.The role of recombinant platelet-activating factor acetylhydrolase in a neonatal rat model of necrotizing enterocolitis. Pediatr. Res. 1997;42:779–83.CrossRefGoogle Scholar
Dvorak, B., Halpern, M. D., Holubec, H.et al.Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model. Am. J. Physiol. Gastrointest. Liver Physiol. 2002;282:G156–64.CrossRefGoogle Scholar
Pitt, J., Barlow, B., Heird, W. C.Protection against experimental necrotizing enterocolitis by maternal milk. I. Role of milk leukocytes. Pediatr. Res. 1977;11:906–9.CrossRefGoogle Scholar
Carlson, S. E., Montalto, M. B., Ponder, D. L., Werkman, S. H., Korones, S. B.Lower incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids. Pediatr. Res. 1998;44:491–8.CrossRefGoogle ScholarPubMed
Eibl, M. M., Wolf, H. M., Furnkranz, H., Rosenkranz, A.Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA–IgG feeding. N. Engl. J. Med. 1988;319:1–7.CrossRefGoogle ScholarPubMed
Kliegman, R. M., Pittard, W. B., Fanaroff, A. A.Necrotizing enterocolitis in neonates fed human milk. J. Pediatr. 1979;95:450–3.CrossRefGoogle ScholarPubMed
Willis, D. M., Chabot, J., Radde, I. C., Chance, G. W.Unsuspected hyperosmolality of oral solutions contributing to necrotizing enterocolitis in very-low-birth-weight infants. Pediatrics 1977;60:535–8.Google ScholarPubMed
White, K. C., Harkavy, K. L.Hypertonic formula resulting from added oral medications. Am. J. Dis. Child. 1982;136:931–3.Google ScholarPubMed
Butel, M. J., Roland, N., Hibert, A.et al.Clostridial pathogenicity in experimental necrotising enterocolitis in gnotobiotic quails and protective role of bifidobacteria. J. Med. Microbiol. 1998;47:391–9.CrossRefGoogle ScholarPubMed
Clark, D. A., Thompson, J. E., Weiner, L. B.et al.Necrotizing enterocolitis: intraluminal biochemistry in human neonates and a rabbit model. Pediatr. Res. 1985;19:919–21.CrossRefGoogle Scholar
Clark, D. A., Miller, M. J.Intraluminal pathogenesis of necrotizing enterocolitis. J. Pediatr. 1990;117:S64–7.CrossRefGoogle ScholarPubMed
Schanler, R. J., Shulman, R. J., Lau, C., Smith, E. O., Heitkemper, M. M.Feeding strategies for premature infants: randomized trial of gastrointestinal priming and tube-feeding method [see comments]. Pediatrics 1999;103:434–9.CrossRefGoogle ScholarPubMed
Ryder, R. W., Shelton, J. D., Guinan, M. E.Necrotizing enterocolitis: a prospective multicenter investigation. Am. J. Epidemiol. 1980;112:113–23.CrossRefGoogle ScholarPubMed
Furlano, R. I., Walker, W. A.Immaturity of gastrointestinal host defense in newborns and gastrointestinal disease states. Adv. Pediatr. 1998;45:201–22.Google ScholarPubMed
Bines, J. E., Walker, W. A.Growth factors and the development of neonatal host defense. Adv. Exp. Med. Biol. 1991;310:31–9.CrossRefGoogle ScholarPubMed
Walker, W. A.Role of nutrients and bacterial colonization in the development of intestinal host defense. J. Pediatr. Gastroenterol. Nutr. 2000;30:S2–7.CrossRefGoogle ScholarPubMed
Berseth, C. L.Gestational evolution of small intestine motility in preterm and term infants. J. Pediatr. 1989;115:646–51.CrossRefGoogle ScholarPubMed
Berseth, C. L.Neonatal small intestinal motility: motor responses to feeding in term and preterm infants. J. Pediatr. 1990;117:777–82.CrossRefGoogle ScholarPubMed
Berseth, C. L.Gut motility and the pathogenesis of necrotizing enterocolitis. Clin. Perinatol. 1994;21:263–70.CrossRefGoogle ScholarPubMed
Bueno, L., Ruckebusch, Y.Perinatal development of intestinal myoelectrical activity in dogs and sheep. Am. J. Physiol. 1979;237:E61–7.Google ScholarPubMed
Caplan, M. S., Miller-Catchpole, R., Kaup, S.et al.Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model. Gastroenterology 1999;117:577–83.CrossRefGoogle Scholar
Deitch, E. A.Role of bacterial translocation in necrotizing enterocolitis. Acta Paediatr. Suppl. 1994;396:33–6.CrossRefGoogle ScholarPubMed
Duffy, L. C., Zielezny, M. A., Carrion, V.et al.Concordance of bacterial cultures with endotoxin and interleukin-6 in necrotizing enterocolitis. Dig. Dis. Sci. 1997;42:359–65.CrossRefGoogle ScholarPubMed
Duffy, L. C., Zielezny, M. A., Carrion, V.et al.Bacterial toxins and enteral feeding of premature infants at risk for necrotizing enterocolitis. Adv. Exp. Med. Biol. 2001;501:519–27.CrossRefGoogle ScholarPubMed
Nowicki, P. T., Miller, C. E.Autoregulation in the developing postnatal intestinal circulation. Am. J. Physiol. 1988;254:G189–93.Google ScholarPubMed
Nowicki, P. T., Nankervis, C. A., Miller, C. E.Effects of ischemia and reperfusion on intrinsic vascular regulation in the postnatal intestinal circulation. Pediatr. Res. 1993;33:400–4.Google ScholarPubMed
Nowicki, P. T.Effects of sustained flow reduction on postnatal intestinal circulation. Am. J. Physiol. 1998;275:G758–68.Google ScholarPubMed
Caplan, M., Hsueh, W., Kelly, A., Donovan, M.Serum platelet-activating factor acetylhydrolase increases during neonatal maturation. Prostaglandins 1990;39:705–14.CrossRefGoogle Scholar
Nanthakumar, N. N., Fusunyan, R. D., Sanderson, I., Walker, W. A.Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis. Proc. Natl. Acad. Sci. USA. 2000;97:6043–8.CrossRefGoogle ScholarPubMed
Haller, D., Bode, C., Hammes, W. P.et al.Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut 2000;47:79–87.CrossRefGoogle ScholarPubMed
Kagnoff, M. F.Immunology of the intestinal tract. Gastroenterology 1993;105:1275–80.CrossRefGoogle ScholarPubMed
Laboisse, C. L.Structure of gastrointestinal mucins: searching for the Rosetta stone. Biochimie 1986;68:611–17.CrossRefGoogle ScholarPubMed
Pang, K. Y., Bresson, J. L., Walker, W. A.Development of the gastrointestinal mucosal barrier V. Comparative effect of calcium binding on microvillus membrane structure in newborn and adult rats. Pediatr. Res. 1983;17:856–61.CrossRefGoogle ScholarPubMed
Pang, K. Y., Bresson, J. L., Walker, W. A.Development of the gastrointestinal mucosal barrier. Evidence for structural differences in microvillus membranes from newborn and adult rabbits. Biochim. Biophys. Acta. 1983;727:201–8.CrossRefGoogle ScholarPubMed
Pang, K. Y., Newman, A. P., Udall, J. N., Walker, W. A.Development of gastrointestinal mucosal barrier. VII. In utero maturation of microvillus surface by cortisone. Am. J. Physiol. 1985;249:G85–91.Google ScholarPubMed
Udall, J. N., Pang, K., Fritze, L., Kleinman, R., Walker, W. A.Development of gastrointestinal mucosal barrier. I. The effect of age on intestinal permeability to macromolecules. Pediatr. Res. 1981;15:241–4.CrossRefGoogle Scholar
Udall, J. N. Jr.Gastrointestinal host defense and necrotizing enterocolitis. J. Pediatr. 1990;117:S33–43.CrossRefGoogle ScholarPubMed
Hsueh, W., Caplan, M. S., Sun, X.et al.Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis. Acta Paediatr. Suppl. 1994;396:11–17.CrossRefGoogle ScholarPubMed
Weaver, L. T., Laker, M. F., Nelson, R.Intestinal permeability in the newborn. Arch. Dis. Child. 1984;59:236–41.CrossRefGoogle ScholarPubMed
Smith, S. D., Cardona, M. A., Wishnev, S. A., Kurkchubasche, A. G., Rowe, M. I.Unique characteristics of the neonatal intestinal mucosal barrier. J. Pediatr. Surg. 1992;27:333–8.CrossRefGoogle ScholarPubMed
Snyder, J. D., Walker, W. A.Structure and function of intestinal mucin: developmental aspects. Int. Arch. Allergy Appl. Immunol. 1987;82:351–6.CrossRefGoogle ScholarPubMed
Lin, J., Holzman, I. R., Jiang, P., Babyatsky, M. W.Expression of intestinal trefoil factor in developing rat intestine. Biol. Neonate 1999;76:92–7.CrossRefGoogle ScholarPubMed
Sands, B. E., Podolsky, D. K.The trefoil peptide family. Annu. Rev. Physiol. 1996;58:253–73.CrossRefGoogle ScholarPubMed
Tan, X. D., Hsueh, W., Chang, H., Wei, K. R., Gonzalez-Crussi, F.Characterization of a putative receptor for intestinal trefoil factor in rat small intestine: identification by in situ binding and ligand blotting. Biochem. Biophys. Res. Commun. 1997;237:673–7.CrossRefGoogle ScholarPubMed
Salzman, N. H., Polin, R. A., Harris, M. C.et al.Enteric defensin expression in necrotizing enterocolitis. Pediatr. Res. 1998;44:20–6.CrossRefGoogle ScholarPubMed
Ouellette, A. J.Paneth cells and innate immunity in the crypt microenvironment. Gastroenterology 1997;113:1779–84.CrossRefGoogle ScholarPubMed
Guy-Grand, D., Griscelli, C., Vassalli, P.The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J. Exp. Med. 1978;148:1661–77.CrossRefGoogle Scholar
Rieger, C. H., Rothberg, R. M.Development of the capacity to produce specific antibody to an ingested food antigen in the premature infant. J. Pediatr. 1975;87:515–18.CrossRefGoogle Scholar
Perkkio, M., Savilahti, E.Time of appearance of immunoglobulin-containing cells in the mucosa of the neonatal intestine. Pediatr. Res. 1980;14:953–5.CrossRefGoogle ScholarPubMed
Roberts, S. A., Freed, D. L.Neonatal IgA secretion enhanced by breast feeding. Lancet 1977;2:1131.CrossRefGoogle ScholarPubMed
Villalpando, S., Hamosh, M.Early and late effects of breast-feeding: does breast-feeding really matter?Biol. Neonate. 1998;74:177–91.CrossRefGoogle ScholarPubMed
Wold, A. E., Adlerberth, I.Breast feeding and the intestinal microflora of the infant – implications for protection against infectious diseases. Adv. Exp. Med. Biol. 2000;478:77–93.CrossRefGoogle ScholarPubMed
Lee, W. J., Farmer, J. L., Hilty, M., Kim, Y. B.The protective effects of lactoferrin feeding against endotoxin lethal shock in germfree piglets. Infect. Immun. 1998;66:1421–6.Google ScholarPubMed
Neu, J., Roig, J. C., Meetze, W. H.et al.Enteral glutamine supplementation for very low birth weight infants decreases morbidity. J. Pediatr. 1997;131:691–9.CrossRefGoogle ScholarPubMed
Neu, J., DeMarco, V., Li, N.Glutamine: clinical applications and mechanisms of action. Curr. Opin. Clin. Nutr. Metab. Care 2002;5:69–75.CrossRefGoogle ScholarPubMed
Neurath, M. F., Fuss, I., Kelsall, B. L.et al.Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. J. Exp. Med. 1996;183:2605–16.CrossRefGoogle ScholarPubMed
Riegler, M., Sedivy, R., Sogukoglu, T.et al.Effect of growth factors on epithelial restitution of human colonic mucosa in vitro. Scand. J. Gastroenterol. 1997;32:925–32.CrossRefGoogle ScholarPubMed
Juul, S. E., Joyce, A. E., Zhao, Y., Ledbetter, D. J.Why is erythropoietin present in human milk? Studies of erythropoietin receptors on enterocytes of human and rat neonates. Pediatr. Res. 1999;46:263–8.CrossRefGoogle ScholarPubMed
Ledbetter, D. J., Juul, S. E.Erythropoietin and the incidence of necrotizing enterocolitis in infants with very low birth weight. J. Pediatr. Surg. 2000;35:178–82.CrossRefGoogle ScholarPubMed
Dai, D., Nanthkumar, N. N., Newburg, D. S., Walker, W. A.Role of oligosaccharides and glycoconjugates in intestinal host defense. J. Pediatr. Gastroenterol. Nutr. 2000;30:S23–33.CrossRefGoogle ScholarPubMed
Tanaka, M., Lee, K., Martinez-Augustin, O.et al.Exogenous nucleotides alter the proliferation, differentiation and apoptosis of human small intestinal epithelium. J. Nutr. 1996;126:424–33.CrossRefGoogle ScholarPubMed
Bisset, W. M., Watt, J. B., Rivers, R. P., Milla, P. J.Ontogeny of fasting small intestinal motor activity in the human infant. Gut 1988;29:483–8.CrossRefGoogle ScholarPubMed
Lawrence, G., Bates, J., Gaul, A.Pathogenesis of neonatal necrotising enterocolitis. Lancet 1982;1:137–9.CrossRefGoogle ScholarPubMed
Peter, C. S., Feuerhahn, M., Bohnhorst, B.et al.Necrotising enterocolitis: is there a relationship to specific pathogens?Eur. J. Pediatr. 1999;158:67–70.CrossRefGoogle Scholar
Tomkins, A. M., Bradley, A. K., Oswald, S., Drasar, B. S.Diet and the faecal microflora of infants, children and adults in rural Nigeria and urban U. K. J. Hyg. (Lond). 1981;86:285–93.CrossRefGoogle ScholarPubMed
Rubaltelli, F. F., Biadaioli, R., Pecile, P., Nicoletti, P.Intestinal flora in breast- and bottle-fed infants. J. Perinat. Med. 1998;26:186–91.CrossRefGoogle ScholarPubMed
Gewolb, I. H., Schwalbe, R. S., Taciak, V. L., Harrison, T. S., Panigrahi, P.Stool microflora in extremely low birthweight infants. Arch. Dis. Child. Fetal Neonatal Edn. 1999;80:F167–73.CrossRefGoogle ScholarPubMed
Mehall, J. R., Kite, C. A., Saltzman, D. A.et al.Prospective study of the incidence and complications of bacterial contamination of enteral feeding in neonates. J. Pediatr. Surg. 2002;37:1177–82.CrossRefGoogle ScholarPubMed
Yoshimura, A., Lien, E., Ingalls, R. R.et al.Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 1999;163:1–5.Google ScholarPubMed
Deitch, E. A., Specian, R. D., Berg, R. D.Endotoxin-induced bacterial translocation and mucosal permeability: role of xanthine oxidase, complement activation, and macrophage products. Crit. Care Med. 1991;19:785–91.CrossRefGoogle ScholarPubMed
Birchler, T., Seibl, R., Buchner, K.et al.Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur. J. Immunol. 2001;31:3131–7.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Panigrahi, P., Gupta, S., Gewolb, I. H., Morris, J. G. Jr.Occurrence of necrotizing enterocolitis may be dependent on patterns of bacterial adherence and intestinal colonization: studies in Caco-2 tissue culture and weanling rabbit models. Pediatr. Res. 1994;36:115–21.CrossRefGoogle ScholarPubMed
Hoyos, A. B.Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int. J. Infect. Dis. 1999;3:197–202.CrossRefGoogle Scholar
Alward, C. T., Hook, J. B., Helmrath, T. A., Mattson, J. C., Bailie, M. D.Effects of asphyxia on cardiac output and organ blood flow in the newborn piglet. Pediatr. Res. 1978;12:824–7.CrossRefGoogle ScholarPubMed
Touloukian, R. J., Posch, J. N., Spencer, R.The pathogenesis of ischemic gastroenterocolitis of the neonate: selective gut mucosal ischemia in asphyxiated neonatal piglets. J. Pediatr. Surg. 1972;7:194–205.CrossRefGoogle ScholarPubMed
Schoenberg, M. H., Beger, H. G.Reperfusion injury after intestinal ischemia. Crit. Care. Med. 1993;21:1376–86.CrossRefGoogle ScholarPubMed
Crissinger, K. D.Animal models of necrotizing enterocolitis. J. Pediatr. Gastroenterol. Nutr. 1995;20:17–22.CrossRefGoogle ScholarPubMed
Nankervis, C. A., Nowicki, P. T.Role of endothelin-1 in regulation of the postnatal intestinal circulation. Am. J. Physiol. Gastrointest. Liver Physiol. 2000;278:G367–75.CrossRefGoogle ScholarPubMed
Nankervis, C. A., Nowicki, P. T.Role of nitric oxide in regulation of vascular resistance in postnatal intestine. Am. J. Physiol. 1995;268:G949–58.Google ScholarPubMed
Nowicki, P. T., Hansen, N. B., Hayes, J. R., Menke, J. A., Miller, R. R.Intestinal blood flow and O2 uptake during hypoxemia in the newborn piglet. Am. J. Physiol. 1986;251:G19–24.Google ScholarPubMed
Nowicki, P. T., Minnich, L. A.Effects of systemic hypotension on postnatal intestinal circulation: role of angiotensin. Am. J. Physiol. 1999;276:G341–52.Google ScholarPubMed
Reber, K. M., Nankervis, C. A., Nowicki, P. T.Newborn intestinal circulation. Physiology and pathophysiology. Clin. Perinatol. 2002;29:23–39.CrossRefGoogle ScholarPubMed
Nankervis, C. A., Reber, K. M., Nowicki, P. T.Age-dependent changes in the postnatal intestinal microcirculation. Microcirculation 2001;8:377–87.CrossRefGoogle ScholarPubMed
Caplan, M. S., MacKendrick, W.Inflammatory mediators and intestinal injury. Clin. Perinatol. 1994;21:235–46.CrossRefGoogle ScholarPubMed
Caplan, M. S., Jilling, T.New concepts in necrotizing enterocolitis. Curr. Opin. Pediatr. 2001;13:111–15.CrossRefGoogle ScholarPubMed
O'Neill, L. A.The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE. 2000;2000:RE1.CrossRefGoogle ScholarPubMed
Medzhitov, R.Toll-like receptors and innate immunity. Nature Rev. Immunol. 2001;1:135–45.CrossRefGoogle ScholarPubMed
Read, R. C., Wyllie, D. H.Toll receptors and sepsis. Curr. Opin. Crit. Care. 2001;7:371–5.CrossRefGoogle ScholarPubMed
Tracey, K. J., Beutler, B., Lowry, S. F.et al.Shock and tissue injury induced by recombinant human cachectin. Science 1986;234:470–4.CrossRefGoogle ScholarPubMed
Benveniste, J.platelet-activating factor-acether, an ether phospho-lipid with biological activity. Prog. Clin. Biol. Res. 1988;282:73–85.Google Scholar
Hsueh, W., Gonzalez-Crussi, F., Arroyave, J. L.Sequential release of leukotrienes and norepinephrine in rat bowel after platelet-activating factor. A mechanistic study of platelet-activating factor-induced bowel necrosis. Gastroenterology 1988;94:1412–18.CrossRefGoogle ScholarPubMed
Hsueh, W., Gonzalez-Crussi, F., Arroyave, J. L.Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor. J. Clin. Invest. 1986;78:108–14.CrossRefGoogle ScholarPubMed
Cueva, J. P., Hsueh, W.Role of oxygen derived free radicals in platelet activating factor induced bowel necrosis. Gut 1988;29:1207–12.CrossRefGoogle ScholarPubMed
Ford, H., Watkins, S., Reblock, K., Rowe, M.The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J. Pediatr. Surg. 1997;32:275–82.CrossRefGoogle ScholarPubMed
Hammerman, C., Goldschmidt, D., Caplan, M. S.et al.Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase. J. Pediatr. Gastroenterol. Nutr. 1999;29:69–74.CrossRefGoogle ScholarPubMed
Wallace, J. L., Cirino, G., McKnight, G. W., Elliott, S. N.Reduction of gastrointestinal injury in acute endotoxic shock by flurbiprofen nitroxybutylester. Eur. J. Pharmacol. 1995;280:63–8.CrossRefGoogle ScholarPubMed
Tan, X., Sun, X., Gonzalez-Crussi, F. X., Gonzalez-Crussi, F., Hsueh, W.platelet-activating factor and tumor necrosis factor increase the precursor of NF-kappa B p50 mRNA in mouse intestine: quantitative analysis by competitive PCR. Biochim. Biophys. Acta. 1994;1215:157–62.CrossRefGoogle ScholarPubMed
Sun, X., Rozenfeld, R. A., Qu, X.et al.P-selectin-deficient mice are protected from platelet-activating factor-induced shock, intestinal injury, and lethality. Am. J. Physiol. 1997;273:G56–61.Google Scholar
Takakuwa, T., Endo, S., Inada, K.et al.Assessment of inflammatory cytokines, nitrate/nitrite, type II phospholipase A2, and soluble adhesion molecules in systemic inflammatory response syndrome. Res. Commun. Mol. Pathol. Pharmacol. 1997;98:43–52.Google ScholarPubMed
Caplan, M. S., Hedlund, E., Adler, L., Lickerman, M., Hsueh, W.The platelet-activating factor receptor antagonist WEB 2170 prevents neonatal necrotizing enterocolitis in rats. J. Pediatr. Gastroenterol. Nutr. 1997;24:296–301.CrossRefGoogle ScholarPubMed
Caplan, M. S., Sun, X. M., Hseuh, W., Hageman, J. R.Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J. Pediatr. 1990;116:960–4.CrossRefGoogle ScholarPubMed
Caplan, M. S., Sun, X. M., Hsueh, W.Hypoxia, platelet-activating factor, and necrotizing enterocolitis. Lipids 1991;26:1340–3.CrossRefGoogle ScholarPubMed
Hsueh, W., Gonzalez-Crussi, F., Arroyave, J. L.Platelet-activating factor-induced ischemic bowel necrosis. An investigation of secondary mediators in its pathogenesis. Am. J. Pathol. 1986;122:231–9.Google ScholarPubMed
Gonzalez-Crussi, F., Hsueh, W.Experimental model of ischemic bowel necrosis. The role of platelet-activating factor and endotoxin. Am. J. Pathol. 1983;112:127–35.Google ScholarPubMed
Rabinowitz, S. S., Dzakpasu, P., Piecuch, S.et al.Platelet-activating factor in infants at risk for necrotizing enterocolitis. J. Pediatr 2001;138:81–6.CrossRefGoogle ScholarPubMed
Mozes, T., Braquet, P., Filep, J.Platelet-activating factor: an endogenous mediator of mesenteric ischemia-reperfusion-induced shock. Am. J. Physiol. 1989;257:R872–7.Google ScholarPubMed
Sun, X. M., Hsueh, W.Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J. Clin. Invest. 1988;81:1328–31.CrossRefGoogle ScholarPubMed
Caplan, M. S., Sun, X. M., Hsueh, W.Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (platelet-activating factor-acether). Gastroenterology 1990;99:979–86.CrossRefGoogle Scholar
Edelson, M. B., Bagwell, C. E., Rozycki, H. J.Circulating pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis. Pediatrics 1999;103:766–71.CrossRefGoogle ScholarPubMed
Lindsay, J. O., Ciesielski, C. J., Scheinin, T., Hodgson, H. J., Brennan, F. M.The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10. J. Immunol. 2001;166:7625–33.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×