Nonmuscle Myosin IIA Regulates Platelet Contractile Forces Through Rho Kinase and Myosin Light-Chain Kinase.

Platelet contractile forces play a major role in clot retraction and help to hold hemostatic clots against the vessel wall. Platelet forces are produced by its cytoskeleton, which is composed of actin and nonmuscle myosin filaments. In this work, we studied the role of Rho kinase, myosin light-chain kinase, and myosin in the generation of contractile forces by using pharmacological inhibitors and arrays of flexible microposts to measure platelet forces.

Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion.

Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug.

Mode of delivery in pregnancies complicated by preeclampsia with very low birth weight infants.

The aims of this study were to examine data from an institution at which the goal has been to pursue vaginal delivery in patients with a preterm gestation and preeclampsia and to test the hypothesis that labor does not increase the risk of poor outcome for the preterm infant of a mother with preeclampsia. An analysis of all singleton infants born live who weighed 1500 gm or less and who were born to mothers with preeclampsia or eclampsia from 1975 to 1990 was undertaken. The infants who were delivered by cesarean section without labor and with a reassuring fetal assessment were compared with the infants who went through labor.

Cost effects of surfactant therapy for neonatal respiratory distress syndrome.

Objective: To examine the cost effects of a single dose (5 ml/kg) of a protein-free synthetic surfactant (Exosurf) as therapy for neonatal respiratory distress syndrome, for both rescue and prophylactic therapy.

Research Design: Nonblinded, randomized clinical trials of both rescue and prophylactic therapy. Regression analyses were used to control for the independent effects of sex, multiple birth, delivery method, birth weight, and surfactant therapy.

Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease.

EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .

Outcome of very-low-birth-weight infants exposed to beta-sympathomimetics in utero.

In this study we examined neonatal and early childhood outcomes after intrauterine exposure to beta-sympathomimetic agents on infants with birth weights less than or equal to 1500 gm. The hospital courses and anthropomorphic, developmental, and neurologic development of 201 infants exposed to one or more beta-sympathomimetic agents (isoxsuprine, 33; ritodrine, 70; terbutaline, 43; combination, 55) were analyzed and compared with those of 130 control infants of similar birth weight. One hundred and seventy-seven infants had follow-up to 1 year of age, 101 to age 3, and 58 to age 4.

Stridor and gastroesophageal reflux in infants.

A relation was found between persistent stridor and gastroesophageal reflux in seven infants, aged 6 weeks to 6 months. Stridor began at 11 days to 2 months of age, and four of the seven infants had transient hypercarbia on at least one occasion before study. Only one had a history of frequent vomiting; three had recurrent pneumonia.

Neonatal status and hearing loss in high-risk infants.

Neurophysiologic and behavioral assessments of auditory function were performed on 224 very low birth weight (less than or equal to 1500 gm) infants requiring intensive care in the nursery. The subjects were studied prospectively from 36 weeks to 4 years of age, as available for follow-up. To classify them according to their neonatal status, we applied a principal components analysis to a number of variables representative of the extent of illness and of patient care in early postnatal life.

Very low birth weight infants at 8 and 11 years of age: role of neonatal illness and family status.

The intellectual and educational status of 108 children with very low birth weight (less than or equal to 1,500 g), born from 1965 to 1978, was evaluated and tested on standard tests (eight children with severe handicaps were excluded) at 8 years of age. Fifty-seven were further evaluated at 11 years of age. Six categorical outcomes were defined a priori, based on the Wechsler Intelligence Scale for Children-Revised IQ and discrepancies between Verbal and Performance scores and Bender Gestalt Test score.

Neonatal status: an objective scoring method for identifying infants at risk for poor outcome.

The likelihood of sustaining neurological, sensory or cognitive deficits is considerably greater for very low birthweight (VLBW) infants who require intensive care in early postnatal life than those without major neonatal illness. Identifying which, if any, medical events are responsible for an adverse outcome is most difficult in the face of multiple concurrent complications. In this research, a principal components analysis was performed in order to arrive at a set of orthogonal variables which succinctly described clinical involvement in the nursery.

An acute reduction in the fraction of inspired oxygen increases airway constriction in infants with chronic lung disease.

Infants with chronic lung disease have acute episodes of hypoxemia that are often accompanied by wheezing. To test whether a sudden reduction in FIO2 might increase airway obstruction in such infants, we measured the flow-volume relationship, O2 saturation, and skin-surface CO2 tension in 19 sedated infants, 11 with chronic lung disease, and 8 control infants, before and during 10 min of continuous hypoxemia. In the infants with chronic lung disease, a 20 to 25% reduction in FIO2 caused acute hypoxemia (O2 saturation, 77 +/- 8%) and an associated decrease in mid-expiratory flow from 103 +/- 55 to 69 +/- 37 ml/s (mean +/- SD; p less than 0.

Developmental outcome following posthemorrhagic hydrocephalus in preterm infants. Comparison of twins discordant for hydrocephalus.

The mental development and neurologic outcome of four sets of preterm twins, in whom one infant within each pair developed posthemorrhagic hydrocephalus during the neonatal period, were assessed. Each hydrocephalic infant presented with signs of increased intracranial pressure and required placement of a ventriculoperitoneal shunt. Three of the four hydrocephalic infants required revision or replacement of the shunt during the first year.

Lung function in prematurely delivered rabbits treated with a synthetic surfactant.

We treated prematurely delivered rabbit pups with the synthetic surfactant that has been named Exosurf. By weight, Exosurf is 61.8% dipalmitoylphosphatidylcholine, 6.

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers.

Chronic lung disease in prematurely born infants, defined as the need for increased inspired oxygen at 28 days of age, was thought to be more common in some institutions than in others. To test this hypothesis, we surveyed the experience in the intensive care nurseries at Columbia and Vanderbilt Universities, the Universities of Texas at Dallas, Washington at Seattle, and California at San Francisco, the Brigham and Women's Hospital in Boston, Texas Children's Hospital in Houston, and Mt Sinai Hospital in Toronto. The survey included 1,625 infants with birth weights of 700 to 1,500 g.

Estimation of ventilatory response to carbon dioxide in newborn infants using skin surface blood gas electrodes.

Using only skin surface blood gas measurements, we calculated the ventilatory response to inhaled carbon dioxide from changes in skin surface PCO2 (PSCO2). This new method is based on the fact that if CO2 elimination is nearly constant, the change in alveolar ventilation from one steady state level to another is inversely proportional to the change in PSCO2. From this we derived a ventilatory ratio (VR) for 0%, 2%, and 4% CO2 breathing.

Esophageal spasm associated with apnea and bradycardia in an infant.

A newborn infant was found to have diffuse esophageal spasm in association with apnea and bradycardia. This association has not been physiologically documented before. The infant's condition improved after the administration of glycopyrrolate, an anticholinergic agent.

Changes in phospholipid composition of lung surfactant during development in the fetal lamb.

The lung surfactant isolated from pulmonary fluid of fetal sheep changes both in amount and composition during gestation. Total phosphatidylcholine (PC) and its most surface-active components, disaturated PC, are present at very low levels 3-4 weeks prior to term and rise to adult levels 3-4 days before birth. The acidic phospholipids appear with a different time course.

Inhibition of breathing movements in fetal sheep by prostaglandins.

We studied the effects of infusions (duration 13.4 +/- 2.9 h) of prostaglandins (PG) on fetal breathing movements (FBM) in 12 fetal sheep at 122-141 days gestation.

Developmental profiles for the brainstem auditory evoked potential.

Brainstem auditory evoked potentials (BAEP's) were recorded from 641 subjects in eleven age groups ranging from birth through adulthood, including three levels of prematurity, in order to establish an age-specific normative data base. The amplitude and latency values for waves 1-6, interwave differences for 3-1, 5-3, 5-1 and the amplitude ratios for 5/3 and 5/1 were then converted to percentile scores to permit construction of age-related BAEP profile report forms. Visual inspection of the printed output reveals the proportion of subjects falling above and below a given individual across all BAEP measures.

An intercostal retractometer for estimation of intrapleural pressure changes in infants.

An intercostal retractometer was developed for estimation of intrapleural pressure changes in infants. It consists of a flat reference plate which floats over the interspace and is attached to the skin by a flexible plastic film. The pressure inside the device is measured with a strain gauge.

Effect of oxygen administration during sleep on skin surface oxygen and carbon dioxide tensions in patients with chronic lung disease.

Hypoxemia, hypercarbia, and cor pulmonale ultimately occur in most patients with chronic lung disease. Although oxygen therapy may reduce or delay the development of pulmonary hypertension and myocardial failure in these patients, its use is thought to lead to CO2 narcosis and apnea. The effect of O2 administration during sleep has been examined in 12 patients (seven with cystic fibrosis, three with bronchopulmonary dysplasia, one with bronchiolitis obliterans, and one with severe hypersensitivity pneumonitis) using skin surface O2 (Roche) and CO2 (Radiometer) electrodes.

Effect of naloxone on ventilation in newborn rabbits.

Endorphins have been isolated from amniotic fluid and cord blood of mammals. To determine if these agents influence ventilation after birth, we measured ventilation (VE), tidal volume, inspiratory time, and respiratory frequency (f) in 19 rabbit pups before and after administration of naloxone (NLX), an endorphin antagonist. Tracheostomy and carotid artery cannulation were performed under light ether anesthesia.

Continuous measurements of skin surface oxygen and carbon dioxide tensions in obstructive sleep apnea.

We have found that skin surface electrodes for continuously measuring oxygen (PSO2) and carbon dioxide (PSCO2) tensions provide reliable means of determining whether infants with apnea due to airway obstruction during sleep require treatment. Nine patients referred for evaluation of aqnea during sleep were studied. In 6 patients with PSO2 less than 50 torr during sleep, the hypoxic episodes were clearly associated with partial or total airway occlusion as judged by increasing respiratory effort without concomitant airflow.