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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The infiltration of an organ or tissue by neutrophils is the hallmark of acute inflammation. Recent work from many laboratories suggests that neutrophils may play a role in the development of tissue injury in a variety of disease states in the gastrointestinal tract. These diseases include gastritis, necrotizing enterocolitis, ileitis, ulcerative colitis, and ischemia reperfusion injuries. In view of this recent interest in the neutrophil and its relationship to GI diseases, it seems timely to review what is known about neutrophil recruitment to the gastrointestinal tract. This review will therefore focus on the sojourn of the neutrophil from the circulation to its destination in the GI tract.
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PMID:Neutrophil recruitment to the gastrointestinal tract. 152 57

Several reports have suggested indomethacin administration causes necrotizing enterocolitis (NEC) in infants. Few experimental studies have addressed this relationship. We studied the effects of indomethacin after temporary intestinal ischemia in CD-1 mice, using a previously reported method of simulating NEC in mice. This involved occlusion of both superior mesenteric vessels for 15 minutes. Three groups were studied. In group 1, 12 mice had superior mesenteric vessels occluded for 15 minutes, followed by intravenous (IV) administration of saline for three doses over 3 days. In group 2, 12 mice had sham laparotomy, without occlusion of vessels, followed by IV administration of indomethacin for three doses over 3 days. In group 3, 36 mice had mesenteric vessel occlusion for 15 minutes, followed by IV administration of indomethacin for three doses over 3 days. The results were as follows: group 1, bowel necrosis developed in 1 of 12 animals (8%); group 2, all 12 animals survived without bowel damage (0%); and group 3, 22 of 36 animals developed bowel necrosis (61%) (Fisher's Exact Test: occlusion alone v occlusion and indomethacin, P = .002; indomethacin alone v occlusion and indomethacin, P = .00015.) We conclude that whereas occlusion alone or indomethacin alone does not cause bowel necrosis, temporary intestinal occlusion followed by indomethacin causes bowel necrosis in over 60% of animals studied. In the shocked preterm infant who may have suffered temporary intestinal ischemia, administration of indomethacin may be the second step to development of NEC.
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PMID:Indomethacin administration after temporary ischemia causes bowel necrosis in mice. 164 Mar 21

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.
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PMID:Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis. 169 96

The most common gastrointestinal emergency in the newborn is necrotizing enterocolitis. Premature babies are the most likely victims, but it also occurs in full-term infants. Although great strides have been made in elucidating some of the factors responsible for necrotizing enterocolitis, such as intestinal ischemia, bacterial overgrowth, and feeding dysfunction, the exact etiology is as yet unclear. The timing and indications for surgery differ from institution to institution, but the long-term outcome is similar in most large series. The overall mortality rate remains about 20% to 40%, and of the survivors, about one half seem to have no sequelae, the remaining infants having neurologic and gastrointestinal deficits of various degrees of significance.
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PMID:Necrotizing enterocolitis in infancy. 173 87

Ischemia-reperfusion injury has been implicated as playing a major role in the development of necrotizing enterocolitis, a major cause of morbidity and mortality in the newborn. A tungsten-supplemented molybdenum-free diet can reduce xanthine oxidase (XO) enzyme activity in the intestine, which in turn reduces the generation of oxygen radicals after an ischemia-reperfusion insult. This study evaluated the ability of this diet to be effective by indirect means, ie, transplacental and breast-feeding routes. XO activity of the intestine was measured in three groups of CD-1 white rats: I, weanlings fed the tungsten diet or standard chow for 1 week; II, 1-day-old rat pups whose mothers were maintained on the tungsten or standard chow for 7 to 10 days prior to term; and III, rat pups at 1 and 3 weeks after birth whose lactating mothers were maintained on the tungsten or standard chow. Some animals from group III also underwent either a 30- or 60-minute episode of occlusion of the superior mesenteric artery (SMA) to evaluate the protective effects of the diet. XO activity was significantly reduced in all groups receiving the tungsten diet (P less than .0001). Blinded histopathologic studies of the entire small bowel showed significantly less villar necrosis (P less than .05) and fibrosis (P less than .0001) in the tungsten-treated group than in the controls. In the 60-minute occlusion study all tungsten-group animals survived, whereas 7 of 12 in the control group died of intestinal infarction within 24 hours (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A tungsten-supplemented diet delivered by transplacental and breast-feeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischemia-reperfusion injury to the small intestine. 191 86

With the advent of modern neonatology and the survival of most premature infants, necrotizing enterocolitis of the newborn (NEC) has become a relatively frequent illness. NEC, although affecting mainly premies, may still be found in any infant, even full term ones. We therefore believe that it is important for all physicians to become somewhat familiar with this entity. The pathogenesis of NEC is comprised of several variables: mesenteric ischemia, gastrointestinal immaturity, enteral feedings and even possibly infection. A diagnosis of NEC is based on a combination of clinical and radiological grounds. On radiographs, pneumatosis intestinalis and air in the portal vein are of special significance. NEC is classified in three broad categories: suspected NEC, definite NEC and advanced NEC. The treatment is either medical or surgical, depending on the severity and the evolution of the disease. It is important to emphasize that any infant who is deteriorating deserves very tight clinical and radiological follow-up. This follow-up should take place in a center where pediatric surgeons are ready to intervene rapidly should there be a need. Even if in some cases NEC is very severe, sometimes fatal, approximately 85% of infants suffering from it survive and among them more than 70% do so without any long term sequelae.
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PMID:[Necrotizing enterocolitis of the newborn. Review for the clinician]. 196 80

Necrotizing enterocolitis, a severe gastrointestinal disease in the neonatal period, affects primarily premature infants. Perinatal complications that predispose the neonate to systemic hypoxia are frequent in infants with necrotizing enterocolitis. Ischemia of the intestinal mucosa may facilitate the invasion of enteric microorganisms in stressed low birth weight infants. Geographical and temporal clustering of outbreaks of the disease and the termination of epidemics by standard infection control underline the importance of infectious agents in the development of this disease. Several studies have established the immunoprotective effect of orally administered antibodies against infection of the gastrointestinal mucosa in children and adults. Anecdotal evidence suggested that feeding of human immune globulin might have a positive effect on the incidence of necrotizing enterocolitis in premature infants. This paper reviews a prospective, randomized, controlled trial of the efficacy of an oral immune globulin preparation (published in detail in the New England Journal of Medicine, Vol. 319, pp 1-7, 1988) and discusses the pathogenic role of infection in necrotizing enterocolitis.
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PMID:Prophylaxis of necrotizing enterocolitis by oral IgA-IgG: review of a clinical study in low birth weight infants and discussion of the pathogenic role of infection. 208 93

Reactive oxygen metabolites have been implicated in the pathogenesis of mucosal injury induced by ischemia-reperfusion in adult animals, with recent interest centering on the capacity of polymorphonuclear neutrophil-derived oxidants to mediate this injury. A role for oxidants has also been postulated in the etiology of neonatal necrotizing enterocolitis. Based on evidence that the intrinsic capacity of the neonatal piglet intestine to detoxify hydrogen peroxide (H2O2) is minimal relative to that of older piglets, we characterized the changes in mucosal permeability induced by luminal perfusion with H2O2 and hypochlorous acid at concentrations that can be produced physiologically by activated neutrophils (0.05 mmol/L, 0.1 mmol/L, and 0.5 mmol/L), in the distal ileum of 1-d- and 1-mo-old piglets. Mucosal permeability was quantitated by measurement of blood-to-lumen clearance of 51-labeled chromium EDTA. Luminal perfusion with either H2O2 (0.05 mmol/L and 0.1 mmol/L) or hypochlorous acid (0.1 mmol/L and 0.5 mmol/L) significantly increased mucosal permeability in newborn piglets but did not affect mucosal permeability in 1-mo-old animals. Perfusion with 0.5 mmol/L H2O2 significantly increased mucosal permeability over control values in both age groups, but injury in the newborn intestine was significantly greater than that observed in 1-mo-old animals. Thus, as predicted by the reduced intrinsic capacity of the mucosa of neonatal piglets to detoxify H2O2, the ileum of newborn piglets is more vulnerable to oxidant-induced mucosal injury than is the ileum of older animals.
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PMID:Oxidant-induced increases in mucosal permeability in developing piglets. 216 84

To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis (NEC), we assigned a total of 466 women admitted in premature labor either to receive placebo (group A, n = 256), if delivery was expected to occur within 24 hours of admission, or to receive betamethasone (group B, n = 210) if delivery was expected to take place more than 24 hours after admission. All women were free of severe medical complications or drug therapy; cases of intrauterine growth retardation or premature rupture of the membranes were excluded. Their newborn infants, excluding malformed, congenitally infected, and growth-retarded infants, were enrolled in the study unless they had died before the age of 10 postnatal days. Babies born to group A mothers (n = 248) were further assigned to a treatment group (group A1, n = 130) receiving dexamethasone, 2 mg/kg/day by intravenous injection during the first 7 days of life, or to a control group (group A2, n = 118) receiving 10% dextrose solution placebo. Group B infants (prenatal betamethasone, n = 205) received neither treatment nor placebo. The incidence of NEC in group A1 was 6.9% (9/130), and in group A2 it was 14.4% (17/118) (p less than 0.05). In group B the incidence was 3.4% (7/205); this was much lower than in group A2 (p less than 0.01) and lower than in group A combined (10.4%) (p less than 0.01). There was no death from NEC and no surgical intervention among group B patients. The mortality rate for group A1 (11%) was lower than for group A2 (56%) (p less than 0.02). There were fewer indications for surgical intervention for NEC in group A1 than in group A2. Histologic studies confirmed bowel ischemia in all specimens analyzed. These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment. Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy, it improves clinical outcome of NEC.
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PMID:Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. 219 55

We reviewed pathology specimens from 84 patients seen during a 10-year period with neonatal necrotizing enterocolitis, and these findings were correlated with clinical features. Coagulation (ischemic) necrosis, inflammation, and bacterial overgrowth were all present in the intestine of nearly all patients but with individual variability in the severity of these findings. Overall, coagulation necrosis was more severe than any other finding in most infants, indicating the importance of ischemia in the pathophysiology of necrotizing enterocolitis. Reparative tissue changes such as epithelial regeneration, granulation tissue formation, and fibrosis, found in two thirds of cases, suggested ongoing tissue injury of at least several days' duration. Birth weight, Apgar score, age, feeding status, and the presence of respiratory distress syndrome were not correlated with any particular histologic feature. The pathologic changes of necrotizing enterocolitis suggest that its cause is multifactorial, with ischemia, inflammation, bacterial overgrowth, and reparative tissue changes all playing important roles.
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PMID:Pathology of neonatal necrotizing enterocolitis: a ten-year experience. 236 30


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