Publications (86) View all
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Article: Role of glucagon-like peptide-2 deficiency in neonatal short bowel syndrome using neonatal piglets.
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ABSTRACT: Background:Short bowel syndrome (SBS) is the most common cause of neonatal intestinal failure. Recovery requires intestinal adaptation, dependent on enteral nutrition (EN) and growth factors like glucagon-like peptide-2 (GLP-2), secreted from L cells in the ileum. The usual causes of neonatal SBS often result in loss of ileum; therefore we hypothesized that without ileum, endogenous GLP-2 production would be inadequate to promote adaptation. We compared endogenous GLP-2 production and adaptation in neonatal animals with SBS, with and without ileum.Methods:Neonatal piglets (4-6 days) were randomized to 75% mid-intestinal resection; 75% distal-intestinal resection; or sham control without resection. Postoperatively, all piglets commenced parenteral nutrition (PN), tapering as EN was increased to maintain specific growth.Results:The resected SBS piglets developed intestinal failure, requiring a longer duration of PN support and having fat malabsorption. The piglets without ileum were not able to wean from PN during the study and did not show adaptation, specifically growth in intestine length or crypt hyperplasia on histology of the jejunum. Adaptation was observed in the resected SBS piglets with ileum and these piglets also had an increased in plasma GLP-2 that was not observed in piglets without ileum.Conclusions:SBS piglets with ileum have adaptation, associated with increased endogenous GLP-2 production. SBS piglets without ileum have limited adaptation and severe intestinal failure, requiring prolonged PN support. This appears to be related to a deficiency in endogenous GLP-2 production.Pediatric Research (2013); doi:10.1038/pr.2013.44.Pediatric Research 03/2013; · 2.70 Impact Factor -
Article: The Use of Peripherally Inserted Central Catheters For Long-Term Parenteral Nutrition In Infants With Intestinal Failure.
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ABSTRACT: BACKGROUND:: Infants with intestinal failure often require long-term central access for delivery of parenteral nutrition (PN). Traditionally, surgically placed, central venous catheters (CVCs) have been used. However, the complications associated with these catheters can lead to significant morbidity. Peripherally-inserted central catheters (PICCs) are potentially superior to CVCs because they tend to be smaller, and can be placed without general anesthesia. The purpose of this study is to report the use of PICCs for long-term administration of PN in infants with intestinal failure and compare with previously published catheter infection and venous thrombosis rates. METHODS:: A four year review of infants <12 months of age with intestinal failure and a PICC for PN delivery was performed to determine the incidence of catheter-related bloodstream infections (CRBSI) and PICC associated venous thrombosis. The complication rates were compared to those reported for CVCs and PICCs in the pediatric literature. RESULTS:: 45 infants with intestinal failure, receiving PN through a PICC were included in the study. Data from 95 PICCs accounting for 10189 catheter days was collected. The overall incidence of CRBSI was 5.3 per 1000 catheter days and the incidence of venous thrombosis was 2.0 per 1000 catheter days. CONCLUSIONS:: PICCs offer an advantage over CVCs in that they can often be inserted without a general anesthesia and do not require manipulation of the vein. Given the low rate of CRBSI and venous thrombosis we recommend PICCs for infants with intestinal failure requiring PN.Journal of pediatric gastroenterology and nutrition 12/2012; · 2.18 Impact Factor -
Article: Prevention of catheter-related blood stream infections in children with intestinal failure.
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ABSTRACT: PURPOSE OF REVIEW: Catheter-related bloodstream infections (CRBSIs) account for a major source of morbidity in children with intestinal failure. Many of these patients require long-term central venous access, placing them at significant risk for these infections. The purpose of this review is to highlight the most current strategies and interventions for minimizing CRBSIs in this population. RECENT FINDINGS: Strategies for the prevention of CRBSIs continue to evolve, although most have not been specifically evaluated in children with intestinal failure. Some of the more recent interventions that are likely to be effective in this population include creating standardized protocols for catheter insertion and maintenance, ethanol lock therapy, and occasional use of antimicrobial catheters and dressings. SUMMARY: Every effort must be made to prevent CRBSIs in infants and children with intestinal failure. Disease specific risk factors must be considered when determining the best approach for infection prevention. Because of their long-term access needs, checklists and protocols to maintain strict sterile technique at the time of catheter insertion are useful. Additionally, these children often have some degree of intestinal bacterial overgrowth secondary to dilation and dysmotility. Therefore, the use of antimicrobial locks, catheters and dressings likely provide benefit for some patients.Current opinion in gastroenterology 09/2012; · 4.33 Impact Factor -
Article: Effect of nitrous oxide exposure during surgery on the homocysteine concentrations of children.
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ABSTRACT: Nitrous oxide converts vitamin B12 to its nonmetabolically active form, inhibits methionine synthase, and results in an elevation of plasma total homocysteine (tHcy). The authors investigated the effect of nitrous oxide anesthesia on the plasma tHcy concentrations in children the morning after surgery and whether blood concentrations of folate and vitamins B12 and B6 were associated with any potential increase. The authors measured plasma tHcy concentrations in 32 children before and 24 h after initial exposure to nitrous oxide (≥ 2 h). Genotype for methylenetetrahydrofolate reductase C677T and blood concentrations of folate, vitamins B12 and B6, and methylmalonic acid were measured before surgery. The median age of participants was 11 months (3-126 months). The median (first, third quartile) postoperative plasma tHcy concentration was significantly higher than the preoperative concentration (6.4 [4.7, 8.9] vs. 5.1[4.1, 6.4] μM, P < 0.0001), a 25% (2%, 42%) relative increase. Six of 28 (21%) children with normal, age-appropriate, preexposure plasma tHcy concentrations had postoperative plasma tHcy concentrations greater than the cutoff values. The duration of nitrous oxide exposure was associated positively with the rise in plasma tHcy concentration (R2 = 0.696, P = < 0.001). Exposure to ≥ 2 h nitrous oxide is associated with a small, albeit statistically significant, increase in postoperative plasma tHcy concentrations the morning after surgery in young children. The clinical significance of this increase is unknown.Anesthesiology 05/2012; 117(1):15-21. · 5.36 Impact Factor -
Article: Novel lipid-based approaches to pediatric intestinal failure-associated liver disease.
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ABSTRACT: Historically, intestinal failure-associated liver disease (IFALD) has been the greatest contributor to the morbidity experienced by children with intestinal failure. Although the cause of IFALD is multifactorial, recently much attention has been devoted to the critical role that intravenous lipid emulsions play in the development of IFALD. This attention has prompted an interest in alternate approaches to the provision of intravenous lipid in children with IFALD. The 2 approaches that have been advanced are that of lipid minimization and alternate intravenous lipid emulsions, including those containing ω-3 fatty acids. This article examines the rationale and current evidence for these approaches in children with intestinal failure. Our overall finding is that although these alternate approaches show significant promise, they have primarily been studied in uncontrolled settings, mainly in children with advanced IFALD. As such, we believe that there remains a lack of definitive evidence for their efficacy. Furthermore, important safety parameters remain to be evaluated, including the effect of these therapies on growth and development. Therefore, there is currently insufficient evidence to support the use of these novel therapies as standard of care in children with no or early IFALD with the goal of preventing the progression of liver disease.Archives of pediatrics & adolescent medicine 05/2012; 166(5):473-8. · 3.73 Impact Factor
