Clinical determinants of intestinal failure and death in preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B.On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15-0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02-3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26-6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death.

Chronic stress produces enduring decreases in novel stress-evoked c-fos mRNA expression in discrete brain regions of the rat.

Chronic stress produces numerous adaptations within the hypothalamic-pituitary-adrenal (HPA) axis that persist well after cessation of chronic stress. We previously demonstrated profound attenuation of HPA axis responses to novel environment 4-7 days following chronic stress. The present study tests the hypothesis that this HPA axis hyporesponsivity is associated with reductions in stress-evoked c-fos mRNA expression, a marker of neuronal activation, in discrete brain regions. Adult male Sprague-Dawley rats underwent 1 week of chronic variable stress (CVS), with unhandled rats serving as controls. Independent groups of control and CVS rats were exposed to novel environment at 16 h, 4 days, 7 days, or 30 days after CVS. Marked reductions of c-fos mRNA expression in the CVS group persisted for at least 30 days within the paraventricular nucleus of the hypothalamus, and for at least 1 week in rostroventrolateral septum and lateral hypothalamus. Lower levels of c-fos mRNA expression were observed at 16 h recovery in the ventrolateral medial preoptic area, basolateral amygdala, anterior cingulate cortex, and prelimbic cortex. The results demonstrate long-term alterations in neuronal activation within neurocircuits critical for regulation of physiological and psychological responses to stressors.

Environmental context and drug history modulate amphetamine-induced c-fos mRNA expression in the basal ganglia, central extended amygdala, and associated limbic forebrain.

The context in which amphetamine is administered modulates its ability to induce both behavioral sensitization and immediate early gene expression. When given in a novel test environment amphetamine produces greater levels of c-fos and arc mRNA expression in many brain regions relative to when it is given in the home cage. The purpose of the current study was to determine if environment and drug history interact to influence amphetamine-induced c-fos mRNA expression. Rats with a unilateral 6-hydroxydopamine lesion were treated for 7 days with saline or 0.5 mg/kg of d-amphetamine (i.v.) in a distinct and relatively novel test environment (Novel), or in their home cage (Home). Following a 10-12-day withdrawal period, a challenge injection of either saline or 0.5 mg/kg d-amphetamine was administered. In situ hybridization histochemistry was used to examine c-fos mRNA expression in several regions of the basal ganglia, the central extended amygdala, and limbic forebrain. In most brain regions amphetamine given in the Novel environment produced greater c-fos mRNA expression than when given it was given at Home, and drug history had no effect on amphetamine-induced c-fos mRNA expression. However, within the subthalamic nucleus, substantia nigra reticulata, and central nucleus of the amygdala prior experience with amphetamine in the Novel but not Home environment enhanced the effect of an amphetamine challenge injection on c-fos mRNA expression. In contrast, there was a decrease in c-fos mRNA expression in amphetamine-pretreated animals, regardless of environmental context, in the ventral portion of the far caudal striatum. Reexposure to an environment previously paired with amphetamine produced a conditioned increase in c-fos mRNA expression in portions of the caudate-putamen, the subthalamic nucleus, the nucleus accumbens shell and a conditioned decrease in c-fos mRNA expression in the central nucleus of the amygdala. We conclude that environmental context and drug history interact to alter the basal ganglia and central extended amygdala circuitry engaged by subsequent exposure to amphetamine, or exposure to an environment previously paired with amphetamine.