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Biomedical subjects

W Long

Publications and source records attributed to W Long.

At least 91 records · Page 5Linked to original sources

A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

BACKGROUND: Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants. METHODS: We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo. RESULTS: Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055). CONCLUSIONS: In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.

Birth Weight↗

Decreased mortality rate among small premature infants treated at birth with a single dose of synthetic surfactant: a multicenter controlled trial. American Exosurf Pediatric Study Group 1.

To determine whether a single prophylactic dose of synthetic surfactant would reduce mortality and morbidity rates, we performed a randomized, controlled trial of Exosurf Neonatal at 19 hospitals in the United States. The Exosurf preparation (5 ml/kg) was instilled into the endotracheal tube of premature infants weighing 700 to 1100 gm during mechanical ventilation, as soon as practical after birth. Control infants were treated with air (5 ml/kg). Dose administration was performed in secrecy by clinicians who did not reveal for 2 years what they had instilled. A total of 222 infants received air and 224 received the synthetic surfactant; 36 infants with congenital pneumonia or malformations were excluded from the primary efficacy analysis. By the age of 28 days, there were 44 deaths in the air group and 27 deaths in the surfactant group (p = 0.022). By the age of 1 year after term there were 61 deaths in the air group and 35 deaths in the surfactant group (p = 0.002). Although there was no reduction in the incidence of respiratory distress syndrome, a significant reduction in the number of deaths attributed to respiratory distress syndrome, a significant reduction in the incidence of pulmonary air leaks, and significantly lower requirements for oxygen and mean airway pressure indicated that lung disease was less severe in the Exosurf-treated infants. There were no significant differences in the incidence of complications such as bronchopulmonary dysplasia, intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and infection. The results indicate that a single prophylactic dose of Exosurf, in high-risk premature infants treated soon after birth, reduces the number of deaths from respiratory distress syndrome and the overall mortality rate.

Bronchopulmonary Dysplasia↗

Effects of two rescue doses of a synthetic surfactant on mortality rate and survival without bronchopulmonary dysplasia in 700- to 1350-gram infants with respiratory distress syndrome. The American Exosurf Neonatal Study Group I.

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 21 American hospitals, two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air were administered to 419 infants weighing 700 to 1350 gm who had respiratory distress syndrome and an arterial/alveolar oxygen pressure ratio less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to those infants remaining on ventilatory support. Infants were stratified at entry by birth weight and gender. Among infants receiving synthetic surfactant, improvements in alveolar-arterial oxygen pressure gradient, arterial/alveolar oxygen pressure ratio, and oxygen and ventilator needs through 7 days of age were apparent. Death from respiratory distress syndrome was reduced by two thirds (21 vs 7; p = 0.007), and the overall neonatal mortality rate was reduced by half (50 vs 23; p = 0.001). Although there was no significant reduction in the incidence of bronchopulmonary dysplasia (39 vs 31; p = 0.107), the hypothesis that survival through 28 days without bronchopulmonary dysplasia would be enhanced by two rescue doses of synthetic surfactant was proved true (21% improvement, from 132 to 156 patients; p = 0.001). In addition, the incidence of pneumothorax was reduced by one third (62 vs 40; p = 0.022), and the incidence of pulmonary interstitial emphysema was reduced by half (102 vs 51; p = 0.001). The only side effect identified was an increase in the incidence of apnea (102 vs 134; p = 0.001). These findings indicate that rescue use of a synthetic surfactant can improve the morbidity and mortality rates for premature infants with respiratory distress syndrome.

Bronchopulmonary Dysplasia↗

Hemodynamic effects of endothelin-1 in the newborn piglet: influence on pulmonary and systemic vascular resistance.

The aim of this study was to investigate the influence of endothelin-1 (ET-1) on the pulmonary and systemic circulations in newborn piglets. Twelve piglets (mean age of 6.8 days, range of 1-12 days) were anesthetized with chloralose-urethane and ventilated at FiO2 = 1.0. Animals were instrumented to measure cardiac output (CO), pulmonary artery pressure (PAP), aortic pressure (AoP), left atrial pressure (LAP), and right atrial pressure (RAP). Six piglets received a control saline injection into the pulmonary artery (PA), and six piglets received one injection of ET-1 (500 ng/kg) into the PA while PAP, AoP, LAP, RAP, CO, and heart rate (HR) were measured simultaneously at 20-s intervals with pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) calculated by computer. Administration of ET-1 into the PA led to (a) a transient decrease in mean PAP (delta max of -4 +/- 2 mm Hg, p less than 0.001); (b) a biphasic response (an initial decline followed by a substantial increase) in PVR (delta max of -760 +/- 460 dyn cm/s5, p less than 0.01, and delta max of +1,490 +/- 1,360 dyn cm/s5, p less than 0.05) and in AoP (delta max of -12 +/- 7 mm Hg, p less than 0.005, and delta max of +11 +/- 6 mm Hg, p less than 0.005); (c) an increase in SVR (delta max of +5,930 +/- 2,330 dyn cm/s5, p less than 0.05); and (d) an initial increase in CO (delta max of +0.06 +/- 0.03 L/min, p less than 0.05) followed by a decrease (delta max of -0.09 +/- 0.05 L/min, p less than 0.05). These responses have not been observed in adult species and may indicate a developmental difference in the response of the pulmonary circulation to ET-1 administration.

Animals↗

Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial.

STUDY OBJECTIVE: To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension. DESIGN: Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months. SETTING: Four referral centers. PATIENTS: Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema). INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics. MEASUREMENTS AND MAIN RESULTS: Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system. CONCLUSIONS: Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease.

Adolescent↗

Improved outcome at 28 days of age for very low birth weight infants treated with a single dose of a synthetic surfactant.

Two identical double-blind, controlled, randomized trials were initiated to determine whether the administration of a single 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal), soon after the delivery of infants with birth weights 700 to 1350 gm, would improve rates of survival without bronchopulmonary dysplasia. Both trials were terminated before enrolling their planned sample sizes because of the availability of Exosurf under the provisions of a Treatment Investigational New Drug program. We report the combined results of these trials. Study infants were stratified according to birth weight and gender before random assignment to a treatment regimen. One hundred ninety-two infants received Exosurf and 193 received an air placebo. The study groups were similar when a variety of demographic features describing the mothers, their pregnancies, the circumstances of the births, and the infants were compared. Exosurf-treated infants required significantly less oxygen and respiratory support during the first 3 days of life in comparison with the air-treated infants. Fewer infants in the Exosurf group had pulmonary interstitial emphysema (26 vs 13; p = 0.028). In the Exosurf group, there was a significant reduction in the combined outcome, neonatal death or survival with bronchopulmonary dysplasia (57 vs 39; p = 0.042), and there was a significant increase in rates of survival without this disease (128 vs 137; p = 0.042). There were no differences between treatment groups in the incidences of a variety of complications of prematurity, including apnea, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. We conclude that improvements in respiratory physiology after a single prophylactic dose of Exosurf result in an increased likelihood of neonatal survival without bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗

Prostacyclin and acetylcholine as screening agents for acute pulmonary vasodilator responsiveness in primary pulmonary hypertension.

Epoprostenol sodium (prostacyclin) administered intravenously is considered the standard for assessing the ability of the pulmonary circulation to vasodilate. At present, epoprostenol sodium is an investigational drug that has limited availability. In contrast, acetylcholine, also a pulmonary vasodilator, is readily available. Therefore, we assessed the feasibility of using acetylcholine as an alternative to prostacyclin in testing for the capacity of the pulmonary vasculature to vasodilate. Twenty-three patients with primary pulmonary hypertension (mean pulmonary arterial pressure, 58.5 +/- 13.4 mm Hg) received incremental infusions of prostacyclin and acetylcholine to predetermined maximal infusion rates as part of a battery of vasodilator agents administered according to standard protocols (mean, 5.4 +/- 1.2 agents/patient; range, 3-8 agents/patient); the administration of the different agents was timed to avoid synergistic effects. Of all the agents tested, prostacyclin and acetylcholine were most consistently effective in evoking acute pulmonary vasodilation, and both seemed to distinguish patients capable of manifesting acute pulmonary vasodilation from those who were not. However, at maximal doses set by protocol, prostacyclin generally elicited a greater vasodilator response than acetylcholine. The difference in magnitude of response may have been due to use of prescribed dosages of acetylcholine that were submaximal. In other respects, the two agents were similar; both were equally well-tolerated, and side effects were mild and resolved rapidly when the vasodilator infusions were stopped. We conclude that in the majority of patients with primary pulmonary hypertension, acetylcholine appears to be an effective and available substitute for prostacyclin in screening for pulmonary vasodilator responsiveness.

Acetylcholine↗

Production and detection of coliphage T4 endonuclease V polyclonal and monoclonal antibodies using staphylococcal protein-A hybrid proteins.

To facilitate the production of antibodies against endonuclease V, a pyrimidine dimer-specific DNA glycosylase produced in bacteriophage T4-infected Escherichia coli, we constructed plasmids containing protein-A-endonuclease V fusion genes under control of the E. coli tac promoter. Induction with isopropyl-beta-D-thiogalactopyranoside produced large amounts of fusion proteins, which could easily be purified on human IgG agarose columns. The affinity-purified fusion proteins were injected into rabbits and mice to produce polyclonal and monoclonal antibodies, and also used for the screening of the monoclonal antibodies. These antibodies recognized endonuclease V on immunoblots, and also inhibited the DNA-glycosylase activity in vitro. Epitope mapping of monoclonal antibodies showed that they all (6/6) recognized determinants in the C-half of endonuclease V. A convenient way to detect primary antibodies on nitrocellulose was also developed using a crude protein extract containing protein-A-beta-galactosidase fusion protein and subsequent detection with a mixture of dyes.

Antibodies, Monoclonal↗

Pneumocystis pneumonia in hospitals: outbreaks or improved recognition?

A presumed outbreak of Pneumocystis carinii pneumonitis occurred at a large teaching hospital. The diagnosis was made by lung biopsy or at autopsy in seven patients over a 22 1/2-year period and only by percutaneous lung aspirate in seven patients over a 2 1/2-year period. Apparent outbreaks may be related to both an increase in the number of cases of disease and improved diagnostic methods.

Adult↗

Separation of barbiturates using reverse-phase thin-layer chromatography.

A procedure for separating barbiturates by reverse-phase TLC is described. A spotted TLC plate is dipped in mineral oil/petroleum ether (1:10) and run 15 cm in a solvent of water/methanol/ammonium hydroxide, (80:20:2). After visualization, the drugs tested showed distinct separation.

Barbiturates↗

Laser meridional refractometry.

Laser meridonal refractions were undertaken on 30 subjects. The results were compared to classical subjective techniques utilizing both correlative statistics and clinical criteria. The laser meridional techniques were highly correlated with the subjective procedures and were accurate when judged by clinical criteria.

Adolescent↗

Treatment of flail chest. Use of intermittent mandatory ventilation and positive end-expiratory pressure.

For the past two years we have treated patients with flail chest injuries and concomitant respiratory failure with intermittent mandatory ventilation (IMV) and positive end-expiratory pressure (PEEP). Prior to 1972 these patients were treated with controlled mechanical ventilation (CMV) until gross flailing ceased and inspiratory force and vital capacity measurements were adequate. We retrospectively studied the charts of 37 consecutive patients to compare the length of mechanical ventilatory support of patients managed by conventional CMV with those ventilated with IMV and PEEP. The mean ventilation time of patients treated with IMV and PEEP (5.1 +/- 4.7 days) was significantly less than that of the patients treated with CMV (18.8 +/- 14.4 days) (P less than .001).

Accidents, Traffic↗