The impact of changing neonatal respiratory management on extracorporeal membrane oxygenation utilization.

BACKGROUND: The introduction of inhaled nitric oxide (INO) and high-frequency oscillatory ventilation (HFV) has had a profound effect on the use of extracorporeal membrane oxygenation (ECMO) for respiratory failure in neonates without congenital diaphragmatic hernia (CDH). The purpose of this study was to evaluate the changes in the demographics and outcome of non-CDH neonates who underwent ECMO for hypoxemic respiratory failure. METHODS: All neonates (non-CDH and noncardiac) who underwent ECMO between January 1, 1989 and January 1, 2001 were reviewed. Patients were separated into 3, 4-year periods for comparison (period A, 1989 through 1992; B, 1993 through 1996; C, 1997 through 2000). Data were examined by analysis of variance and contingency table analysis. RESULTS: There was a progressive decline in the total number of neonates requiring ECMO over time (period A, 172; B, 114; C, 56; P <.01). The utilization of pre-ECMO alternate respiratory therapies such as INO (period A, 0%; B, 23%; C, 98%; P <.01) and HFV (period A, 9%; B, 61%; C, 89%; P <.01) have increased significantly associated with an increase in the age of ECMO initiation (Period A, 40.5 hours; B, 58.3 hours; C, 68.5 hours; P <.01). The length of ECMO run also has increased (period A, 154.7 hours; B, 193.0 hours; C, 174.5 hours; P <.01), but the overall mortality rate has remained unchanged. CONCLUSIONS: With the increasing use of INO and HFO, the absolute number of non-CDH, noncardiac neonates with hypoxemic respiratory failure requiring ECMO has decreased. Initiation of ECMO has become progressively later likely because of the use of these rescue therapies, but the overall mortality rate remains unchanged despite this delay.

Laparoscopic removal of an abdominal extralobar pulmonary sequestration.

Extralobar pulmonary sequestrations are rare congenital anomalies that fall into the spectrum of broncho-pulmonary-foregut malformations. The authors describe the laparoscopic removal of an infradiaphragmatic sequestration. The lesion initially presented as a suprarenal mass on antenatal ultrasonographic images. The mass was confirmed on postnatal ultrasonography and computer tomographic scanning. It was followed by magnetic resonance imaging until the patient was 28 months old, at which point it was resected. A review of the literature indicates that infradiaphragmatic sequestrations are readily detectable on antenatal ultrasonographic studies. Advances in imaging technology have made it possible in most cases to distinguish sequestrations from other suprarenal masses including neuroblastomas. However, resection provides a definitive diagnosis and remains the treatment of choice. A laparoscopic approach offers the additional benefits associated with minimally invasive techniques.

Technical advances in pediatric laparoscopy have had a beneficial impact on splenectomy.

PURPOSE: The aim of this study was to demonstrate the effects of recent technical advances on the safety and benefits of pediatric laparoscopic splenectomy. METHODS: A retrospective review was conducted of patients undergoing laparoscopic splenectomy from January 1998 to January 2000. Technical advances utilized during this period included the harmonic scalpel, a specialized flexible hilar retractor, a larger, wire-rimmed specimen bag, and lateral patient positioning. RESULTS: Laparoscopic splenectomy was performed successfully on 18 patients aged 3 to 17 years (median, 9). The indications were hereditary spherocytosis (n = 10), idiopathic thrombocytopenic purpura (n = 5), and other (n = 3). Eight patients had concomitant procedures including cholecystectomy (n = 3), resection of an accessory spleen (n = 3), and other (n = 2). The median operating time, including the concomitant procedures, was 125 minutes (range, 70 to 235). Patients tolerated a regular diet on median postoperative day 1 (range, 1 to 3), and 16 were discharged home on or before postoperative day 2. None of the patients required blood product transfusion or conversion to an open technique. There were no complications, and all patients had returned to usual activity by 2 weeks. CONCLUSION: With recent technological advances, the laparoscopic approach has become easy to perform, safe, and should be considered the procedure of choice for pediatric splenectomy.

Esophagogastric disconnection for gastroesophageal reflux in children with severe neurological impairment.

PURPOSE: Fundoplication has been used successfully to treat gastroesophageal reflux in the pediatric population; however, the results are poorer in those children with neurological impairment. We propose an alternative approach to the needs of these special patients and report the use of esophagogastric disconnection to control reflux in children with profound neurological impairment. METHODS: Between 1991 and 1997, 27 esohagogastric disconnections were performed. All patients were severely neurologically impaired with symptomatic gastroesophageal reflux confirmed by an upper gastrointestinal radiographic study. There were 16 boys and 11 girls with ages ranging from 6 months to 40 years. Three had undergone previous fundoplications that failed, whereas the remaining underwent esophagogastric disconnection as a primary antireflux procedure. Follow-up ranged from 1 month to 6.3 years (average, 2.8 years). The operative approach used a midline incision. The gastroesophageal junction was divided, and the gastric side was closed. A 30- to 40-cm jejunal limb was prepared for Roux-en-Y reconstruction and brought up to the esophagus in a retrocolic manner. Esophagojejunal and jejunojejunal anastomoses were then performed. A Stamm tube gastrostomy was placed, and the appendix was removed. A pyloroplasty and tube jejunostomy were performed when felt to be clinically indicated. RESULTS: Gastroesophageal reflux symptoms resolved, and bolus feedings were tolerated by all patients. Oral feedings were tolerated except in those children limited by their swallowing abilities. Early postoperative complications occurred in eight patients (30%) with two (7%) requiring reoperation (esophageal leak and enterocolitis). Late reoperation was necessary in four patients (15%) for small bowel obstruction, paraesophagcal hernia, gastrostomy revision, and enterocolitis. There were no perioperative deaths, but three patients (11%) died of late surgical complications (two of small bowel obstructions, and one of improper reinsertion of a gastrostomy tube). Three other children died of unrelated causes. CONCLUSIONS: Esophagogastric disconnection effectively eliminates gastroesophageal reflux while allowing both bolus tube feedings and oral supplementation. This operation provides an alternative method of controlling gastroesophageal reflux in children with profound neurological impairment.

The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors.

The immunophilin FKBP12 is an evolutionarily conserved abundant protein; however, its physiological roles remain poorly defined. Here we report that FKBP12 is a common cytoplasmic interactor of TGF beta family type I receptors. FKBP12 binds to ligand-free TGF beta type I receptor, from which it is released upon a ligand-induced, type II receptor mediated phosphorylation of the type I receptor. Blocking FKBP12/type I receptor interaction with FK506 nonfunctional derivatives enhances the ligand activity, indicating that FKBP12 binding is inhibitory to the signaling pathways of the TGF beta family ligands. Overexpression of a myristylated FKBP12 in Mv1Lu cell specifically inhibits two separate pathways activated by TGF beta, and two point mutations on FKBP12 (G89P, I90K) abolish the inhibitory activity of FKBP12, suggesting that FKBP12 may dock a cytoplasmic protein to the type I receptors to inhibit TGF beta family mediated signaling.

The p21(RAS) farnesyltransferase alpha subunit in TGF-beta and activin signaling.

The alpha subunit of p21(RAS) farnesyltransferase (FNTA), which is also shared by geranylgeranyltransferase, was isolated as a specific cytoplasmic interactor of the transforming growth factor-beta (TGF-beta) and activin type I receptors with the use of the yeast two-hybrid system. FNTA interacts specifically with ligand-free TGF-beta type l receptor but is phosphorylated and released upon ligand binding. Furthermore, the release is dependent on the kinase activity of the TGF-beta type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-beta and activin involve novel mechanisms of serine-threonine receptor phosphorylation-dependent release of cytoplasmic interactors and regulation of the activation of small G proteins, such as p21(RAS).

Localization of choline acetyltransferase to somata of posterior lateral line efferents in the goldfish.

The somata of posterior lateral line efferents in goldfish have been identified by retrograde transport of horseradish peroxidase. Co-localization of retrogradely transported horseradish peroxidase and choline acetyltransferase, detected by immunohistochemical staining with the monoclonal antibody AB8, supports the view that some lateral line efferent neurons in the goldfish are cholinergic.