Faculty Bibliography

We describe a case of postoperative uvular edema in a pediatric patient who underwent general anesthesia via a laryngeal mask airway at our institution. Although numerous cases of uvular trauma have been reported in the literature, its association with laryngeal mask airway use remains rare.

Objectives/Aim: To determine the incidence, risk factors, and causes of endotracheal reintubation in children and identify methods to reduce the occurrence. Background: Reintubation during the perioperative period is a serious and potentially preventable adverse event that can result in significant morbidity. Methods: A total of 28 208 anesthetics were delivered to pediatric patients at our institution between May 2006 and May 2009. Reintubations were identified with our quality assurance (QA) surveillance database coupled with chart review by our QA nurse. Cases were classified as planned versus inadvertent extubations, and adverse events were assessed. Results: We discovered 27 cases of reintubation with an incidence of 9.6 : 10 000 anesthetics. Reintubated patients were found to be younger than the general population (P = 0.001) with a high rate of comorbid disease. While most reintubations could be attributed to respiratory causes, 30% were attributed to inadvertent displacement of the endotracheal tube. No mortalities were seen, but 22% of patients needed resuscitative medications and 7% received chest compressions. Of the patients who failed planned extubations, 53% were left intubated with an average duration of postoperative intubation of 2.4 +/- 1.9 days. Conclusions: The incidence of endotracheal reintubation in children is low, but can result in significant morbidity. Because of the high frequency of inadvertent extubation, a significant number of reintubations could be prevented with greater care during transfer of patients with endotracheal tubes, and in procedures near the airway. Increased vigilance in younger children is also recommended as children under 3 years old required the majority of the reintubations.

Notch receptors and their ligands play important roles in both normal animal development and pathogenesis. We show here that the F-box/WD40 repeat protein SEL-10 negatively regulates Notch receptor activity by targeting the intracellular domain of Notch receptors for ubiquitin-mediated protein degradation. Blocking of endogenous SEL-10 activity was done by expression of a dominant-negative form containing only the WD40 repeats. In the case of Notch1, this block leads to an increase in Notch signaling stimulated by either an activated form of the Notch1 receptor or Jagged1-induced signaling through Notch1. Expression of dominant-negative SEL-10 leads to stabilization of the intracellular domain of Notch1. The Notch4 intracellular domain bound to SEL-10, but its activity was not increased as a result of dominant-negative SEL-10 expression. SEL-10 bound Notch4 via the WD40 repeats and bound preferentially to a phosphorylated form of Notch4 in cells. We mapped the region of Notch4 essential for SEL-10 binding to the C-terminal region downstream of the ankyrin repeats. When this C-terminal fragment of Notch4 was expressed in cells, it was highly labile but could be stabilized by the expression of dominant-negative SEL-10. Ubiquitination of Notch1 and Notch4 intracellular domains in vitro was dependent on SEL-10. Although SEL-10 interacts with the intracellular domains of both Notch1 and Notch4, these proteins respond differently to interference with SEL-10 function. Thus, SEL-10 functions to promote the ubiquitination of Notch proteins; however, the fates of these proteins may differ