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Biomedical subjects

W Long

Publications and source records attributed to W Long.

At least 19 recordsLinked to original sources

Production of germ-line chimeras in zebrafish by cell transplants from genetically pigmented to albino embryos.

To determine whether embryonic cells transplanted from one zebrafish embryo to another can contribute to the germ line of the recipient, and to determine whether pigmentation can be used as a dominant visible marker to monitor cell transplants, we introduced cells from genetically pigmented (donor) embryos to albino recipients at midblastula stage. By 48 hr many of the resulting chimeras expressed dark pigment in their eyes and bodies, characteristics of donor but not albino embryos. By 4-6 weeks of age pigmentation was observed on the body of 23 of 70 chimeras. In contrast to fully pigmented wild-type fish, pigmentation in chimeras appeared within transverse bands running from dorsal to ventral. Pigmentation patterns differed from one fish to another and in almost every case were different on each side of a single fish. At 2-3 months of age chimeras were mated to albino fish to determine whether pigmented donor cells had contributed to the germ line. Of 28 chimeric fish that have yielded at least 50 offspring each, 5 have given rise to pigmented progeny at frequencies of 1-40%. The donor cells for some chimeras were derived from embryos that, in addition to being pigmented, were transgenic for a lacZ plasmid. Pigmented offspring of some germ-line chimeras inherited the transgene, confirming that they descended from transplanted donor cells. Our ability to make germ-line chimeras suggests that it is possible to introduce genetically engineered cells into zebrafish embryos and to identify the offspring of these cells by pigmentation at 2 days of age.

Albinism

Delayed compliance increase in infants with respiratory distress syndrome following synthetic surfactant.

Recent research has demonstrated that Exosurf (EXSF), a newly synthesized artificial surfactant, increases survival when administered endotracheally to premature infants with RDS. This study examines the effects of EXSF on static respiratory system compliance (Crs). Thirty-four patients received two doses of EXSF in this rescue protocol. Crs (mL/cmH2O/kg) did not significantly change within the first 4 hours after either dose. However, Crs values did increase significantly (paired Student's t-test, P = 0.005) when data collected after the second dose (0.36 +/- 0.13 mL/cmH2O/kg) were compared to first week follow-up data (0.51 +/- 0.21 mL/cmH2O/kg). Crs data collected between 2 and 4 weeks after treatments were again not significantly different from non-concurrent control data collected at 3-4 weeks of life. The measurement of Crs in infants receiving EXSF may have been affected by an increase in lung inflation, which could mask an increase in Crs. We speculate that improved lung inflation may occur with less barotrauma in the first week of life due to surfactant replacement treatment and may in part explain the improved Crs seen at 1 week of age. Many investigators using different surfactants, dosing schedules, and pulmonary function methodologies to evaluate lung mechanics have reported that the improvement in compliance after surfactant treatment usually follows the clinical improvement in gas exchange. Additional studies are needed to explain the mechanism of early improvement following surfactant replacement in infants with RDS.

Drug Combinations

Controlled trial of a single dose of synthetic surfactant at birth in premature infants weighing 500 to 699 grams. The American Exosurf Neonatal Study Group I.

In a multicenter, double-blind, placebo-controlled trial conducted at 23 hospitals in the United States, a single prophylactic 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal) or air placebo was administered shortly after birth to 215 infants with birth weights of 500 to 699 gm. Despite stratification at entry by birth weight and gender, by chance female infants predominated in the air placebo group and male infants predominated in the surfactant group. Among infants receiving synthetic surfactant, improvements in oxygen requirements were significant at 2 hours after birth (p = 0.014) and persisted for 3 days (p = 0.001); improvements in the alveolar-arterial partial pressure of oxygen gradient were significant at 6 hours after birth (p = 0.01) and persisted for 3 days (p = 0.008). Improvements in mean airway pressure were not significant at 2 or at 6 hours after birth (p = 0.622 and 0.083, respectively), but became significant thereafter and persisted for 3 days (p = 0.002). Pneumothorax was reduced by slightly more than half (25 vs 11; p = 0.014); death from respiratory distress syndrome (RDS) was also reduced (26 vs 15; p = 0.046). Overall neonatal mortality, however, was not significantly reduced (58 vs 46; p = 0.102). Other complications of RDS and prematurity were not altered, except that pulmonary hemorrhage occurred significantly more frequently in infants receiving synthetic surfactant (2 vs 12; p = 0.006). These findings indicate that a single prophylactic dose of synthetic surfactant in infants weighing 500 to 699 gm at birth improves lung function, incidence of air leak, and death from RDS but not overall mortality. The only safety problem identified was an increase in pulmonary hemorrhage.

Bronchopulmonary Dysplasia

Energy expenditure during synthetic surfactant replacement therapy for neonatal respiratory distress syndrome.

Little information is available on the energy expenditure of infants with increased work of breathing from respiratory distress syndrome (RDS). A study was carried out to determine whether surfactant replacement therapy modifies respiratory gas exchange in newborn infants with RDS and an arterial-alveolar oxygen tension ratio of less than 0.22. In a double-blind, placebo-controlled, rescue trial, infants received either two 5 ml/kg doses of a synthetic surfactant, Exosurf Neonatal, or air placebo. Of 23 infants ventilated for RDS, 11 were randomly assigned to receive air and 12 to receive surfactant. Oxygen consumption, carbon dioxide production, respiratory quotient, and metabolic rate were measured by computerized, closed-circuit, indirect calorimetry. Concomitantly, transcutaneous oxygen and carbon dioxide tension were continuously recorded. Oxygen consumption and carbon dioxide production remained constant during the period infants received surfactant. In patients randomly assigned to surfactant, a decrease in respiratory quotient was observed after the first (p less than 0.025) but not the second dose. This decrease was possibly related to a change in substrate utilization. The improved clinical outcomes reported among infants receiving surfactant were not accompanied by changes in energy expenditure.

Calorimetry, Indirect

Elastase activity and surfactant protein concentration in tracheal aspirates from neonates receiving synthetic surfactant.

Neutrophil elastase activity and the concentration of surfactant proteins A and B (SP-A, B) were measured in tracheal aspirate fluid from preterm neonates who were treated with the synthetic surfactant Exosurf Neonatal or air placebo in randomized, placebo-controlled, clinical trials. Elastase activity was transiently reduced in surfactant-treated infants on the second day of life, but the reduction was not sustained. In placebo-treated infants with established respiratory distress syndrome, tracheal aspirate SP-A was low on the first day of life and increased with time as respiratory distress syndrome resolved. In infants with respiratory distress syndrome treated with surfactant, significantly higher levels of SP-A were observed by 2 days after treatment and were maintained through at least the sixth day of life. These data suggest that lung inflammation is not increased and that endogenous surfactant secretion may be stimulated, not suppressed, by treatment with synthetic surfactant.

Drug Combinations

Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: an autopsy evaluation. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal.

Autopsy

Retrospective search for bleeding diathesis among premature newborn infants with pulmonary hemorrhage after synthetic surfactant treatment. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal, involving infants with birth weights 700 gm or greater the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To determine whether this apparent increase in pulmonary hemorrhage was the result of a bleeding diathesis, we retrospectively reviewed charts for 39 of 41 infants with clinical pulmonary hemorrhage. The incidence of nonpulmonary bleeding was the same in control- and surfactant-treated infants. Platelet counts, hematocrit values, and the number of transfusions with platelets or red blood cells did not differ between the two groups. There was no evidence that surfactant treatment was specifically associated with a generalized bleeding diathesis.

Double-Blind Method

A system for saturating in vitro preparations with high pressure O2, He, H2, and mixtures.

Saturation of a liquid with gas before perfusing a tissue or cellular preparation under pressure can be achieved by bubbling the gas through the liquid. A container for this purpose that is housed in the pressure chamber with the preparation allows saturation of the liquid under hyperbaric conditions. Sealing the container allows saturation with a gas different from the gas used to compress the pressure chamber. If the pressure within the sealed container is maintained at a slightly higher level, the bubbling gas can also provide the driving force for the liquid to flow to the preparation. Based on this concept, an apparatus was built and tested to pressures of 6.8 MPa. This paper describes the saturator and the associated circuitry used to control bubbling gas pressure relative to the pressure vessel, gas flow through the saturator, and liquid flow to the preparation. A special application in the case of hydrogen gas is described, where this system has added safety advantages.

Equipment Design

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

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