Metabolic-hypoxic modulation of cytokine induction of intestinal endothelial adhesion molecules: Relevance to ischemic injury mediated necrotizing enterocolitis?

BACKGROUND: Necrotizing enterocolitis (NEC) triggers an intense inflammatory response in the neonatal gut associated with cytokine activation, altered nutrient status and intracellular O2-deprivation. Endothelial cell adhesion molecules (ECAMs) play critical roles in driving immune cell infiltration into inflamed gut. Currently, relationships between inflammation, metabolism and ECAM expression remain poorly understood in NEC. We studied the effects of metabolic depletion (aglycemia/ hypoxia) on TNF-α mediated ECAM expression including ICAM-1, MAdCAM-1, VCAM-1 and E-selectin, in vitro in intestinal microvascular endothelial cells (IMEC). METHODS: To study the effects of TNF-α, aglycemia and hypoxia (alone or in combination) IMECs expression of adhesion molecules was studied using cell surface ELISA and immunoblotting. RESULTS: Total VCAM-1 expression was induced TNF-α and by hypoxia + TNF-α, cell surface expression was induced by hypoxia, TNF-α, TNF- α+hypoxia, and TNF- α+hypoxia and aglycemia. Total ICAM-1 increased following TNF- α, TNF- α+hypoxia, hypoxia + aglycemia, and TNF- α+hypoxia + aglycemia. Total MAdCAM-1 protein expression was significantly induced by a combination of TNF-α+hypoxia + aglycemia and cell surface expression induced by TNF- α+hypoxia. Surface expression of E-selectin was induced by TNF- α+aglycemia and TNF- α+hypoxia + aglycemia. CONCLUSION: Energy metabolism influences inflammation induced injury through mobilization of intestinal ECAMs, and may represent an important mechanism in NEC pathology.

Retroperitoneal immature teratoma.

Retroperitoneal immature teratoma is a rare tumor in the newborn infant with only a few instances reported in several case series.(1,2,3) We report a case of retroperitoneal immature teratoma presenting unusually on day one of life with severe abdominal distension and respiratory failure.

Inflammatory signals that regulate intestinal epithelial renewal, differentiation, migration and cell death: Implications for necrotizing enterocolitis.

Necrotizing enterocolitis is a disease entity with multiple proposed pathways of pathogenesis. Various combinations of these risk factors, perhaps based on genetic predisposition, possibly lead to the mucosal and epithelial injury that is the hallmark of NEC. Intestinal epithelial integrity is controlled by a tightly regulated balance between proliferation and differentiation of epithelium from intestinal epithelial stem cells and cellular loss by apoptosis. various signaling pathways play a key role in creating and maintaining this balance. The aim of this review article is to outline intestinal epithelial barrier development and structure and the impact of these inflammatory signaling and regulatory pathways as they pertain to the pathogenesis of NEC.

Neonatal necrotizing enterocolitis: Clinical challenges, pathophysiology and management.

NEC remains a major concern for neonatologists, surgeons, and gastroenterologists due to its high morbidity and mortality. These infants often have poor developmental outcome, and contribute to significant economic burden resulting in marked stress in these families. By developing and adhering to strict feeding protocols, encouraging human milk feeding preferably from the infant's mother, use of probiotics, judicious antibiotic use, instituting blood transfusion protocols, the occurrence of NEC may possibly be reduced. However, because of its multifactorial etiology, it cannot be completely eradicated in the NICUs, particularly in the extremely premature infants. Ongoing surveillance of NEC and quality improvement projects may be beneficial.

Cortical activation during foot movements: II effect of movement rate and side.

Cerebral control of foot movements has received limited study. Functional MRI compared slow with rapid foot movement, and right (dominant) with left foot movement. Brain activation during right, as compared with left, foot movement was larger, with higher amplitude task-related motor cortex signal change, and higher laterality index. Brain activation during fast, as compared with slow, foot movement was larger in cortical and cerebellar areas but smaller in deep gray areas. Some principles of cerebral control of hand movement extend to foot, but exceptions found include that dominant foot movement showed greater activation than did nondominant, and faster foot movements activated bilateral deep gray matter structures less than did slower. Results might have utility in trials of restorative therapies.

Predicting postoperative cardio-pulmonary complications by a test of stair climbing.

OBJECTIVE: To assess whether a test of stair climbing ability could be used to predict the risk of developing postoperative cardiopulmonary complications in patients undergoing general anesthesia. DESIGN: Cohort study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi. The duration of the study was from December 2003 to December 2004. PATIENTS AND METHODS: This study was carried out on consecutive, adult patients presenting for elective thoracic or abdominal surgery under general anesthesia. Pre-operatively, patients were asked to climb a standard staircase. Number of steps climbed was recorded. Those unable to climb stairs due to debilitating cardiac, pulmonary or rheumatologic disease were categorized as 0 stairs climbed. Outcome variables were postoperative cardiopulmonary complications or mortality. Period of follow-up was until hospital discharge. RESULTS: Seventy-eight patients were enrolled, 59 (75.6%) climbed 1 flight of stairs, 19 (24.3%) climbed < 1 flight. All-cause cardiopulmonary complications rate was 26 %. The most frequent complication was lobar atelectasis, followed by bronchospasm and acute MI. The complication rate was 22.8% in those able to climb 1 flight and 40% in those patients who climbed < 1 flight. The group that climbed < 1 flight tended to have complications associated with poor reserves of the cardiopulmonary systems, i.e. pulmonary edema, exacerbation of underlying lung disease. The relative risk of developing complications, if unable to climb at least 1 flight of stairs, was calculated to be 1.8 (95% CI 0.7 - 4.6). CONCLUSION: Stair climbing can be a useful pre-operative tool to predict the risk of postoperative cardiopulmonary complications.