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Biomedical subjects

E L Dobyns

Publications and source records attributed to E L Dobyns.

5 recordsLinked to original sources
PubMed1999

Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure.

OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.

Administration, Inhalation↗
PubMed1994

Enhanced growth capacity of neonatal pulmonary artery smooth muscle cells in vitro: dependence on cell size, time from birth, insulin-like growth factor I, and auto-activation of protein kinase C.

Based on the unique susceptibility of the neonatal pulmonary circulation to hypoxia-induced structural alteration in vivo, we hypothesized that pulmonary artery (PA) smooth muscle cells (SMC) from the neonate would demonstrate enhanced growth capacity in vitro compared to adult cells. To test this hypothesis, matched neonatal and adult bovine SMC were tested for differences in size, serum-stimulated proliferation, susceptibility to senescence, resistance to serum withdrawal, autocrine growth capacity, and responsiveness to a locally important growth factor (insulin-like growth factor I; IGF-I) and an activator of protein kinase C (PKC) (phorbol 12-myristate 13-acetate; PMA). Neonatal PA SMC were smaller, grew faster, reached a higher plateau density, and were less susceptible to senescence. They were more resistant to serum withdrawal, had spontaneous autocrine growth capacity, and were more responsive to IGF-I, PMA, and the combination. Acquisition of increased growth factor responsiveness occurred between d5 and d14 after birth. Increased neonatal growth to IGF-I was associated with reduced IGF-I binding activity, implicating a post-receptor mechanism in enhanced responsiveness. Increased membrane-bound PKC catalytic activity was found in serum-deprived neonatal SMC. This basal increase was equal to that stimulated by 1 nM PMA in adult SMC, a pretreatment that caused these cells to become as responsive to IGF-I as untreated neonatal ones. We conclude that neonatal bovine PA SMC have marked enhancement of growth capacity in vitro, the acquisition of which is dependent on time from birth and is associated with auto-activation of PKC, These increased growth properties detected in vitro may contribute to the striking hyperplasia of neonatal PA SMC found in vivo following hypoxic exposure.

Aging↗
PubMed1994

Eicosanoids decrease with successful extracorporeal membrane oxygenation therapy in neonatal pulmonary hypertension.

Elevated concentrations of eicosanoids have been reported in bronchoalveolar lavage fluid (BALF) and blood of infants with persistent pulmonary hypertension (PPHN), thereby indicating their potential role in its pathophysiology. Extracorporeal membrane oxygenation (ECMO) has improved the outcome in selected infants with PPHN. We hypothesized that ECMO, by alleviating lung injury, would be associated with decreased eicosanoid production and clinical improvement. Twenty-two newborns with PPHN treated with either ECMO or conventional means were studied. Concentrations of TxB2, 6-keto-PGF1 alpha, PGD2, PGE2, LTB4, and LTE4 were serially measured in BALF. Elevated concentrations of all eicosanoids measured were observed in all infants with PPHN at the initiation of ECMO. Eicosanoid concentrations decreased in all infants with a good clinical outcome after ECMO, but they remained elevated in those with a poor outcome. In patients with less severe PPHN, not requiring ECMO, lower concentrations of eicosanoids were observed at initiation of therapy. Eicosanoid levels increased or did not change over the course of conventional treatment. We conclude that eicosanoids are present in high concentrations in infants with PPHN. Iatrogenic factors, including oxygen and barotrauma, appear to correlate with their concentrations. Removal of these factors is associated with decreased production of mediators and clinical improvement.

Acute Disease↗