Prostaglandin E(2) regulates wound closure in airway epithelium.

Repair of the airway epithelium after injury is critical for the maintenance of barrier function and the limitation of airway hyperreactivity. Airway epithelial cells (AECs) metabolize arachidonic acid to biologically active eicosanoids via the enzyme cyclooxygenase (COX). We investigated whether stimulating or inhibiting COX metabolites would affect wound closure in monolayers of cultured AECs. Inhibiting COX with indomethacin resulted in a dose-dependent inhibition of wound closure in human and feline AECs. Specific inhibitors for both COX-1 and COX-2 isoforms impaired wound healing. Inhibitors of 5-lipoxygenase did not affect wound closure in these cells. The addition of prostaglandin E(2) (PGE(2)) eliminated the inhibition due to indomethacin treatment, and the exogenous application of PGE(2) stimulated wound closure in a dose-dependent manner. Inhibition of COX with indomethacin only at initial time points resulted in a sustained inhibition of wound closure, indicating that prostanoids are involved in early wound repair processes such as spreading and migration. These differences in wound closure may be important if arachidonic acid metabolism and eicosanoid concentrations are altered in disease states such as asthma.

Myocardial injury in children with respiratory syncytial virus infection.

OBJECTIVE: Respiratory syncytial virus (RSV) infection is associated with a number of extrapulmonary manifestations, including a sepsis-like syndrome characterized by any combination of hypothermia, fever, apnea, hypovolemia, and myocardial dysfunction. We hypothesized that RSV can have a direct injurious effect on the myocardium of infants and children that can be detected by the presence of cardiac troponin I (cTnI), a highly sensitive and specific marker of myocardial injury, in the blood of patients infected with the virus. DESIGN: Serial cTnI measurements were obtained from patients admitted with documented RSV infection to the pediatric intensive care unit (PICU). PARTICIPANTS: Data were collected and analyzed from 22 RSV infected patients and 11 control patients. RESULTS: Elevated levels of cTnI were detected in 54.5% (12/22) of the study population during their PICU admission. The average cTnI level was significantly higher in the RSV infected group than in controls. There was a significant association between the presence of a positive troponin assay and the occurrence of a cardiovascular event, the need for inotropic support, and the requirement of mechanical ventilation. Patients who required inotropic support had a significantly higher cTnI level than the rest of the study population. CONCLUSION: A large percentage of children admitted to the PICU with RSV infection have myocardial damage as detected by the use of commercially available troponin assays. Additionally, in a portion of these patients, this damage is clinically significant, leading to cardiovascular instability and the need for inotropic support.

Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia.

The presence of a chromosomal translocation in the leukemic cells at diagnosis of acute lymphoblastic leukemia (ALL) in children is associated with a high risk for treatment failure. We have reexamined the relationship between translocations and prognosis in 146 children with ALL who received risk-based therapy such that high-risk patients were treated with intensive drug schedules. In univariate analysis, multiple factors were associated with a relatively poor event-free survival (EFS) including age less than 2 years or greater than 10 years (combined group), WBC count greater than 10 x 10(9)/L, French-American-British (FAB) morphologic classification L2, absence of common ALL antigen (CALLA, CD10) expression, absence of hyperdiploidy with a chromosome number of 50 to 60, and presence of the specific translocations t(4; 11)(q21;q23) or t(9;22)(q34;q11) (combined group). However, there was no disadvantage with respect to EFS in patients with translocations compared with those who lacked translocations (73% at 4 years in both groups). Furthermore, when patients with specific cytogenetic abnormalities for which the prognostic significance has been well established (hyperdiploid 50 to 60, t(4;11), and t(9;22] were removed from the analysis, the remaining group with other translocations had a better EFS than the remaining group lacking translocations, although this was not statistically significant (81% v 65% at 4 years, P = .24). In a multivariate analysis, a model including WBC count and FAB classification was the strongest predictor of EFS. The presence or absence of translocations was not an independent predictor of EFS and did not contribute to the ability of any model to predict EFS. In conclusion, when effective intensive therapy is used to treat childhood ALL with high-risk clinical features, categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor.