ABSTRACT
INTRODUCTION: Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are neonatal intestinal emergencies that affect premature infants. Although most cases of early NEC can be successfully managed with medical therapy, prompt surgical intervention is often required for advanced or perforated NEC and FIP. METHODS: The surgical management and treatment of FIP and NEC are discussed on the basis of literature review and our personal experience. RESULTS: Surgical options are diverse, and include peritoneal drainage, laparotomy with diverting ostomy alone, laparotomy with intestinal resection and primary anastomosis or stoma creation, with or without second-look procedures. CONCLUSIONS: The optimal surgical therapy for FIP and NEC begins with prompt diagnosis and adequate fluid resuscitation. It appears that there is no significant difference in patient outcome based on surgical management alone. However, the infant's weight, comorbidities, surgeon preference and timing of intervention should be taken into account before operative intervention.
Subject(s)
Enterocolitis, Necrotizing/surgery , Evidence-Based Medicine , Infant, Premature, Diseases/surgery , Infant, Very Low Birth Weight , Intestinal Perforation/surgery , Professional Competence , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/mortality , Gestational Age , Humans , Infant, Newborn , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/mortality , Intestinal Perforation/diagnosis , Intestinal Perforation/mortality , Randomized Controlled Trials as Topic , Resuscitation , Survival RateABSTRACT
c-Cbl-associating protein (CAP) is a multifunctional signaling protein that interacts with c-Cbl, facilitating the tyrosine phosphorylation of c-Cbl in response to insulin. In 3T3-L1 adipocytes and diabetic rodents, CAP gene expression is stimulated by activators of peroxisome proliferator activator receptor gamma (PPARgamma), such as thiazolidinediones (TZDs), resulting in increased insulin-stimulated c-Cbl phosphorylation. Sequence analysis of 2.5 kilobases of the 5'-flanking region of the CAP gene reveals a predicted peroxisome proliferator response element (PPRE) from -1085 to -1097. The isolated promoter was functional in 3T3 fibroblasts and adipocytes. Co-transfection of the CAP promoter with PPARgamma and retinoic acid X receptor alpha caused fold stimulation of promoter activity. The TZD rosiglitazone produced an additional 2-3-fold stimulation of the promoter. Deletion of the predicted PPRE from the CAP promoter abolished its ability to respond to rosiglitazone. Gel shift analysis of the putative PPARgamma site demonstrates direct binding of PPAR/retinoid X receptor heterodimers to the PPRE in the CAP gene. These data demonstrate that TZDs directly stimulate transcription of the CAP gene through activation of PPARgamma.
