Targeted resequencing identifies defective variants of decoy receptor 3 in pediatric-onset inflammatory bowel disease.

Genome-wide association studies have implicated common variation at the 20q13 locus in inflammatory bowel disease, particularly for the pediatric Crohn's form. This locus harbors tumor necrosis factor receptor superfamily (TNFRSF6B), encoding a secreted protein, decoy receptor 3 (DcR3), which binds to and neutralizes pro-inflammatory cytokines of the tumor necrosis factor superfamily. We sought to further the evidence of DcR3's role in pediatric IBD by identifying missense mutations with functional significance within TNFRSF6B. We sequenced the exons of the gene in 528 Caucasian pediatric IBD cases and 549 Caucasian healthy controls to establish the frequency of such events in each population. Sequencing revealed that our IBD cohort harbored a greater number of missense variants, yielding an odds ratio of 3.9 (P-value=0.005). Using functional assays, we established that the frequency of mutants defective in secretion from cultured cells was greater in the Crohn's category than in the controls, yielding an odds ratio of 7.1 (P-value=0.004). These results suggest that rare defective variants in TNFRSF6B have a role in the pathogenesis of some cases of IBD and that interventions targeting this group of tumor necrosis factor-family members may benefit patients with IBD.

Rofecoxib administration to paediatric patients undergoing adenotonsillectomy.

BACKGROUND: Rofecoxib is a selective COX-2 inhibitor that does not interfere with platelet function and is associated with fewer bleeding complications than other nonsteroidal anti-inflammatory agents (NSAIDs). Our aims were to evaluate the safety and the efficacy of rofecoxib administration to paediatric patients undergoing adenotonsillectomy (T&A). METHODS: We conducted a double-blind, randomized, placebo-controlled study of rofecoxib in 45 ASA 1-2 patients > or = 4 years of age undergoing outpatient T&A. All patients received midazolam 0.5 mg x kg(-1) (max 15 mg) p.o. and either rofecoxib 1 mg x .kg(-1) (max 25 mg) or placebo p.o. 30 min preoperatively. All patients had a standardized anaesthetic and were extubated awake in the operating room at the conclusion of surgery. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores were obtained on arrival in the postanaesthetic care unit (PACU). Morphine 25 microg x kg(-1) i.v. were administered up to six times for pain in the PACU. Wong-Baker FACES Scales were obtained at discharge from the PACU and the day surgery unit (DSU). Outcome measures included intraoperative estimated blood loss (EBL), pain scores, PACU morphine requirements and discharge times. RESULTS: There were 23 patients in the rofecoxib group and 22 patients in the placebo group. There were no differences between the rofecoxib and placebo groups in terms of bleeding, pain scores, PACU morphine requirements, PACU times or DSU times. CONCLUSION: Rofecoxib administration to paediatric patients undergoing T&A did not result in increased bleeding. Rofecoxib, however, was not found to decrease morphine use or improve pain scores prior to hospital discharge in T&A patients who received intraoperative morphine and acetaminophen.

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

BACKGROUND: Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. METHODS: In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. RESULTS: In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. CONCLUSIONS: Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.

Serum myoinositol concentrations in premature infants fed human milk, formula for infants, and parenteral nutrition.

Myoinositol concentration was studied in serum of 65 neonates and their mothers at the time of birth, in samples of various types of feedings for infants, and in serial serum samples of 15 premature infants receiving human milk, formulas for infants, or parenteral nutrition over a 3-wk period. At birth the serum concentration of myoinositol was greater in neonates than in their mothers (108 +/- 10 vs 52 +/- 6 mumol/L, respectively, means +/- SEM, p less than 0.01). In feedings for infants, the concentrations of myoinositol were significantly greater in human milk than in formulas or parenteral nutrition solutions (1840 +/- 451 vs 420 +/- 110 vs 100 +/- 8 mumol/L, respectively, p less than 0.001). Over a 3-wk period the serum concentration of myoinositol increased in infants receiving human milk but not in those receiving formulas or parenteral nutrition. Serum concentrations of myoinositol in neonates are greater than in adults and are directly influenced by myoinositol intake.

Evaluation on the effects of cutaneous chemical agents by nuclear magnetic resonance techniques.

A change in relaxation times has been determined in skin tissues after administration of hyaluramine, by means of nuclear magnetic resonance. Results are discussed in terms of water redistribution between the free and bound compartment.