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Biomedical subjects

L Gluck

Publications and source records attributed to L Gluck.

At least 19 recordsLinked to original sources

Reintroduction of continuous negative pressure ventilation in neonates: two-year experience.

Continuous negative pressure ventilation utilizes subatmospheric pressure around the thorax to improve oxygenation. It has not been routinely used since the mid-1970s. We treated 37 infants with the combination of continuous negative pressure (CNP) and intermittent mandatory ventilation (IMV), after failing to attain a PaO2 of greater than or equal to 50 torr on IMV alone. Lung diseases included pulmonary interstitial emphysema (PIE), respiratory distress syndrome (RDS), and pulmonary artery hypertension (PAH) due either to meconium aspiration syndrome (MAS) or other causes (non-MAS). All infants had evidence of severe parenchymal pulmonary disease, or pulmonary artery hypertension resulting in persistent hypoxemia and hypotension. In the PIE group, CNP was started later in the course of the disease, and both positive pressure and oxygen were maintained for a longer period. The group of infants with non-MAS PAH required CNP and positive pressure ventilation for the shortest period of time. The infants with PIE also had a greater incidence of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH). In addition, three patients with PIE died. In the non-MAS patients with PAH, no complications and no deaths occurred. The response to CNP was a rapid improvement in oxygenation in all groups with the greatest increase of PaO2 in the non-MAS PAH infants: from 30 torr prior to the initiation of CNP to 140 torr within 30 minutes. No significant changes in pH or PaCO2 occurred in any group. Significant decreases in ventilator rate, mean airway pressure (Paw) and FIO2 in peak inspiratory pressure were possible by 12 hours of CNP.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

Regulation of immune functions by human surfactant.

Human peripheral blood mononuclear cells (MNC) were incubated in vitro with highly purified human surfactant to examine its effect on various T cell functions. Surfactant inhibited DNA synthesis by lymphocytes in response to concanavalin A (Con A), phytohemagglutinin (PHA), and in the autologous mixed lymphocyte reaction (AMLR). In contrast, surfactant had no effect on pokeweed-mitogen (PWM, T cell-dependent B lymphocyte mitogen)-induced DNA synthesis or on interleukin-2 (IL-2) receptor expression on T cells activated with PHA, Con A or PWM. Furthermore, surfactant had either no effect or enhanced (depending upon the concentration of IL-2 used) the response of exogenous recombinant IL-2 on IL-2-dependent T cell line, In vitro addition of recombinant IL-2 corrected the suppressive effect of surfactant on the AMLR. These data show immunosuppressive effect of surfactant on T lymphocyte functions.

DNA

Hypoxanthine: a marker for asphyxia.

It has been hypothesized that hypoxanthine concentrations in the blood of newborn infants are a marker of asphyxia. To test this hypothesis, we measured serum hypoxanthine levels in relationship to perinatal and neonatal asphyxia, and compared arterial hypoxanthine levels with arterial pH and base deficit. We also compared hypoxanthine levels of survivors with those of asphyxiated non-survivors. Forty-two newborns were classified as asphyxiated by either of two methods: 1) Infants from whom umbilical cord hypoxanthine levels were taken were classified as asphyxiated if they had an Apgar score of 6 or less at 1 or 5 minutes, fetal heart rate below 100 beats per minute, or meconium-stained amniotic fluid; and 2) infants from whom peripheral arterial hypoxanthine samples were taken were classified by clinical assessment, whereby one author, blinded to the infants' hypoxanthine levels, prospectively assessed each patient's condition for evidence of asphyxia. Hypoxanthine levels correlated with increased base deficit (P less than .001; r = 0.8) and with decreased pH (P less than .001; r = -0.5). By both of our asphyxia classification methods, hypoxanthine levels were significantly higher (P less than .002) in the asphyxiated groups. We also noted a higher hypoxanthine level in asphyxiated non-survivors as compared with all survivors (P less than .02). We propose that serum hypoxanthine levels may help define asphyxia. Because hypoxanthine, when metabolized by xanthine oxidase, generates oxygen radicals that are highly destructive to tissue, hypoxanthine levels may have important therapeutic implications for asphyxiated patients.

Asphyxia Neonatorum

Effect of surfactant substitution on lung effluent phospholipids in respiratory distress syndrome: evaluation of surfactant phospholipid turnover, pool size, and the relationship to severity of respiratory failure.

The turnover and pool size of surfactant has been studied in animals, but there is little similar information in humans. In the present investigation lung effluent phospholipids were studied in 29 small preterm infants with severe RDS. Thirteen were treated with mechanical ventilation, and 16 additionally received natural human surfactant. The first dose (60 mg surfactant/kg body wt) was given between 2 and 10 h of age, and the surfactant was given again if there was an insufficient response. Together 260 aspirates, recovered during routine suctioning of the airways, were analyzed for phospholipids. Phosphatidylglycerol, present only in exogenous surfactant, was used as a specific marker to estimate the apparent pool size and the half-life of surfactant phospholipid. In addition, the saturated phosphatidylcholine/sphingomyelin ratios were correlated with the ventilatory index (mean airway pressure X fractional inspiratory oxygen/arterial oxygen tension). There was a linear correlation between the ventilatory index and the saturated phosphatidylcholine/sphingomyelin (r approximately -0.70) but no consistent correlation between the ventilatory index and the amount of phospholipids in the aspirate. The saturated phosphatidylcholine/sphingomyelin ratio increased during the surfactant-induced remission of respiratory failure, decreased during the recovery. The control infants tended to have lower saturated phosphatidylcholine/sphingomyelin ratios during the first week than the surfactant-treated infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Half-Life

Correlation of plasma hypoxanthine and catecholamine levels in the umbilical vein.

Hypoxanthine and the catecholamines, dopamine, norepinephrine and epinephrine were determined in umbilical venous cord plasma in 27 term babies delivered vaginally. When correlating hypoxanthine with log epinephrine a weak positive linear correlation was found (r = 0.45, p less than 0.05). The correlation between hypoxanthine and log dopamine showed a significant negative linear correlation (r = -0.65, p less than 0.01). There was also a significant correlation between log epinephrine and pH (r = 0.72, P less than 0.01) and base deficit (r = 0.46, P less than 0.05). In four babies who suffered intrauterine hypoxia, hypoxanthine was significantly elevated compared with non hypoxic babies (21.4 +/- 5.1 versus 6.3 +/- 6.6 mumol/l, P less than 0.01). In these babies norepinephrine (3710 +/- 3888 vs 789 +/- 718 Pg/ml, P less than 0.01) and epinephrine (298 +/- 229 vs 148 +/- 116 Pg/ml, P less than 0.05) were significantly elevated as well, in contrast to dopamine levels (188 +/- 94 vs 169 +/- 134 Pg/ml N. S.). This finding seems to indicate that dopamine synthesis goes down during hypoxia probably because the rate limiting enzyme in dopamine synthesis, tyrosine, hydroxylase, is inhibited in hypoxia.

Catecholamines

Role of myoinositol in regulation of surfactant phospholipids in the newborn.

According to animal studies myoinositol decreases surfactant phosphatidylglycerol and increases phosphatidylinositol. In the present study lung effluent phospholipids and serum myoinositol were analyzed in respiratory distress syndrome (RDS, 19 cases), in other lung disease (6 cases) and in 22 newborn with no lung disease. In addition, myoinositol was studied in amniotic fluid and in serum from umbilical vessels and from maternal vein (15 healthy newborn). There was a significant correlation between the fetal and amniotic fluid levels of myoinositol, but no detectable correlation between fetal and maternal myoinositol. Serum myoinositol was higher in preterm than in term newborns. In healthy newborns there was a negative correlation between lung effluent phosphatidylglycerol (expressed as percent of the phospholipids) and serum myoinositol (r = -0.968), and a positive linear correlation between myoinositol and lung effluent phosphatidylinositol (r = 0.849). In RDS at birth, undetectable phosphatidylglycerol corresponded with high serum myoinositol. During the first 5 neonatal days serum myoinositol either (1) decreased and phosphatidylglycerol appeared, (2) remained high and phosphatidylglycerol correspondingly low in some small preterm infants, or (3) decreased but phosphatidylglycerol did not expectedly increase and disaturated lecithin/sphingomyelin ratio remained low in other small preterm babies. We propose that a premature decrease in serum myoinositol among small preterm infants with RDS is not beneficial, since myoinositol may promote hormone-induced lung maturation and healing of lung damage.

Humans

Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial.

We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome.

Amniotic Fluid

Real time ultrasound diagnosis of hemorrhagic pathological conditions in the posterior fossa of preterm infants.

Real time echoencephalography (RTE) was used to diagnose and serially follow intracranial pathological conditions in the posterior fossa of infants with a gestational age of less than 34 weeks. The posterior fossa was studied in four planes (coronal, modified coronal, sagittal, and parasagittal) with a sector scanner equipped with a high frequency transducer that was placed on the fontanelles and the sutures. Hemorrhagic complications were easily differentiated from normal anatomy. RTE diagnosis was confirmed with computed tomographic scans (5 patients) and postmortem examination of the brain (18 infants). RTE is a precise and noninvasive technique to visualize hemorrhagic and other forms of abnormalities in the infratentorial compartment.

Cerebral Hemorrhage

Lung profile: sex differences in normal pregnancy.

The incidence of respiratory distress syndrome (RDS) is higher in male than in female infants. The lung profiles--lecithin/sphingomyelin (L/S) ratios, percent disaturated (acetone precipitated) lecithin, phosphatidylglycerol, and phosphatidylinositol--were obtained in amniotic fluid during 164 normal pregnancies of 30 or more weeks' gestation. The profiles were evaluated to determine any sex differences in fetal development of the surfactant components. According to regression analysis the L/S ratios for females reached 2:1 at 33.7 weeks, which is 1.4 weeks earlier than males. A similar trend was evident for disaturated lecithin. Phosphatidylglycerol first appeared at 34 weeks' gestation for females and 35 weeks for males. The rate of the increase in phosphatidylglycerol was higher in females than in males. Phosphatidylinositol began to decrease after 36 weeks for females and fell to levels below that of males after 37 weeks' gestation. All four indexes of the lung profile revealed a higher degree of lung maturity in female than in male fetuses during the last two months of normal pregnancy. This explains a higher incidence of RDS in male than in female infants.

Amniotic Fluid

Acceleration of pulmonary surfactant maturation in stresses pregnancies: a study of neonatal lung effluent.

To determine the maturation of pulmonary surfactant at birth, phospholipid patterns in tracheal or pharyngeal aspirates of 54 newborn infants were analyzed by two-dimensional thin-layer chromatography. The compositions of phospholipids and their surface tension-lowering abilities were assessed after gestations with various complications. Preterm infants with respiratory distress syndrome (RDS) lacked phosphatidylglycerol and had lower lecithin/sphingomyelin ratios than infants without RDS. An acceleration of both phosphatidylcholine (lecithin) and phosphatidylglycerol concentrations was observed in 21 preterm infants born after prolonged rupture of the membranes and treatment with isoxuprine. In these infants, the phospholipid pattern of lung effluent was similar to that of term infants even at gestational ages less than or equal to 30 weeks. Biochemical lung maturation was delayed in aneccephalic infants, infants of diabetic mothers, and one infant of a mother with hypothyroidism.

Birth Weight

The lung profile. I. Normal pregnancy.

The lung profile run by two-dimensional thin-layer chromatography is described, including the L/S ratio and the percentages of disaturated acetone precipitated lecithin, PI, and PG. Results show that the accuracy of this profile increases that of the mature L/S ratio value even further, while decreasing the missed predictions with low L/S ratios to only about 7%.

Amniotic Fluid

Significance of phosphatidylglycerol in amniotic fluid in complicated pregnancies.

In normal pregnancy lecithin/sphingomyelin ratios correlate with gestational age. In complicated pregnancies biochemical maturation of fetal lung may be accelerated or delayed, depending upon maternal, fetal, or placental conditions. Surfactant contains other phospholipids besides lecithin, including phosphatidylglycerol (PG), the second major component of mature surfactant. Ninety phospholipid patterns in amniotic fluid were studied by two-dimensional thin-layer chromatography. In uncomplicated pregnancies PG was absent until 37 weeks' gestation, then increased there after. In complicated pregnancies (pre-eclampsia, diabetes Classes D, F, and R, premature rupture of membranes) PG was identified before 35 (as early as 29 weeks' gestation. These results verify accelerated lung maturation in certain complicated pregnancies. No newborn infant developed respiratory distress syndrome in the presence of PG.

Amniocentesis

Patent ductus arteriosus treated with ligation or indomethacin: a follow-up study.

The course and complications of fifty-two infants with patent ductus arteriosus requiring closure were assessed prospectively. Twenty-six infants with a PDA received indomethacin for pharmacologic closure of the PDA, and 26 underwent ligation. The current study analyzes and compares the longitudinal follow-up with respect to somatic growth, neurologic function, psychomotor and mental development, and renal, ophthalmologic, and audiologic function in 21 infants in each group who entered the follow-up. No selective morbidity was attributable to PDA closure with indomethacin when compared to surgically treated infants.

Child Development

The labeling of lung phosphatidylcholine in premature rabbits.

Lung phosphatidylcholine metabolism was studied in vivo in premature rabbits delivered by cesarean section as early in gestation as compatible with prolonged viability (28.9 days). The newborn rabbits initially required supplemental oxygen and had respiratory distress. The amount of phosphatidylcholine isolated from the lung parenchyma changed little over the first 3 days of life, while phosphatidylcholine in the alveolar wash increased in 3 days from 0.05--3.1 mumol/50 g animal. The phosphatidylcholine of the lungs of the premature rabbits was pulse labeled with isotopically labeled palmitic acid, choline, and phosphate given to the pregnant does 10 min before delivery of the newborns. After the initial incorporation period, the total amount of radioactive precursor palmitic acid, choline, or 32P) incorporated into lung phosphatidylcholine did not change for a period of 4 days. Labeled phosphatidylcholine was detected initially in alveolar wash 3 hr after administration of the three precursors and continued to accumulate for many hours. The biological half-life values for lung and alveolar phosphatidylcholine indicated that phosphatidylcholine was turning over very slowly. However, if the effect of dilution on the measured specific activity caused by phosphatidylcholine accumulation was considered, virtually no labeled alveolar or lung phosphatidylcholine disappeared during the 3--4 days of these observations. These results with premature newborn rabbits were similar to those for term newborn rabbits, but different from similar measurements made in the adult rabbit.

Age Factors

Cesarean delivery in a gorilla.

A mature lowland gorilla (Gorilla gorilla) in the Los Angeles Zoo had destroyed 3 successive infants. To avoid a recurrence, active intervention was instituted during its 4th pregnancy. The period of gestation was estimated by physical examination, radiography, and amniocentesis. Intrauterine growth was followed by serial ultrasonographic cephalometry. When fetal maturity was achieved, as determined by amniotic fluid phospholipid profile, the fetus was delivered by cesarean section.

Amniocentesis

Labeling of phosphatidylcholine in the alveolar wash of rabbits in utero.

Radioactive palmitic acid, choline, and phosphate were given to rabbits 28 and 30 days pregnant and the labeling;of phosphatidylcholine in the fetal lung and alveolar wash was studied. Labeled phosphatidylcholine was detected initially in the alveolar wash three hours after isotope administration. The three-hour delay was independent of precursor studied or gestational age, and the radioactive phosphatidylcholine continued to accumulate in the wash fluid for at least 18 hours. Each labeled precursor of phosphatidylcholine sequentially labeled the phosphatidylcholine from microsomal, lamellar body and alveolar wash lung fractions of the 30 day fetal animals.

Animals