Anoxia-induced neuronal injury: role of Na+ entry and Na+-dependent transport.

An important cause of anoxia-induced nerve injury involves the disruption of the ionic balance that exists across the neuronal membrane. This loss of ionic homeostasis results in an increase in intracellular calcium, sodium, and hydrogen and is correlated with cell injury and death. Using time-lapse confocal microscopy, we have previously reported that nerve cell injury is mediated largely by sodium and that removing extracellular sodium prevents the anoxia-induced morphological changes. In this study, we hypothesized that sodium enters neurons via specific mechanisms and that the pharmacologic blockade of sodium entry would prevent nerve damage. In cultured neocortical neurons we demonstrate that replacing extracellular sodium with NMDG+ prevents anoxia-induced morphological changes. With sodium in the extracellular fluid, various routes of sodium entry were examined, including voltage-sensitive sodium channels, glutamate receptor channels, and sodium-dependent chloride-bicarbonate exchange. Blockade of these routes had no effect. Amiloride, however, prevented the morphological changes induced by anoxia lasting 10, 15, or 20 min. At doses of 10 microM-1 mM, amiloride protected neurons in a dose-dependent fashion. We argue that amiloride acts on a Na+-dependent exchanger (e.g., Na+-Ca2+) and present a model to explain these findings in the context of the neuronal response to anoxia.

Rhinovirus infection associated with serious lower respiratory illness in patients with bronchopulmonary dysplasia.

OBJECTIVE: To determine the characteristics of rhinovirus infection in patients with bronchopulmonary dysplasia. SUBJECTS AND METHODS: Between July 1, 1993, and July 1, 1995, 40 patients with bronchopulmonary dysplasia were identified. Viral cultures were obtained in ambulatory patients presenting with an acute respiratory illness requiring hospitalization or in hospitalized patients with a respiratory deterioration. When rhinovirus was isolated epidemiologic data were collected, and the characteristics of the illness, its severity and outcome were noted. Key features of rhinovirus and respiratory syncytial virus (RSV) bronchiolitis were compared. RESULTS: There were 8 cases of lower respiratory tract illness associated with rhinovirus infection in 6 infants (mean age, 7.1 +/- 4.1 months) and 1 child (age, 40 months), an incidence of 0.15 infection/patient year. The mean gestational age and birth weight of these patients were 27.3 (+/- 2.75) weeks and 853 (+/-341) g, respectively. There were 5 males. Four patients needed intensive care unit admission and 1 required mechanical ventilation. By comparison there were 13 cases of RSV bronchiolitis, an incidence of 0.25 infection/patient year. The 2 groups were similar epidemiologically and an equal proportion of patients with rhinovirus and RSV needed intensive care unit admission. A greater percentage of patients with RSV required mechanical ventilation (50% vs. 14%), but this difference was not statistically significant. Three cases of rhinovirus were nosocomial, and 1 infant had a second infection. Four patients required 5 hospitalizations caused by rhinovirus infection, and the mean duration of hospital stay was 11 days. All children had sustained worsening in their respiratory status after rhinoviral illness requiring additional therapy. CONCLUSIONS: Rhinovirus is a common and potentially serious lower respiratory pathogen in bronchopulmonary dysplasia patients. Rhinovirus infection has lasting pulmonary sequelae in these children.

Cystic fibrosis and calcium oxalate nephrolithiasis.

During the past six years, we have treated eight patients with cystic fibrosis (CF) for nephrolithiasis. In seven patients, the stones were comprised of calcium oxalate. Another six patients had calcium oxalate crystalluria. In our CF population of 140 patients, this represents a cumulative incidence of calcium oxalate nephrolithiasis of 5.7 percent and an additional 4.2 percent incidence of crystalluria. Experience with these patients is reviewed. Pancreatic insufficiency was universally associated with nephrolithiasis or crystalluria. Diabetes and cirrhosis were also common. Predisposing factors and potential mechanisms of stone disease in pancreatic insufficient CF patients are discussed, focusing on the relationship between fat malabsorption in CF to oxalate metabolism.