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Biomedical subjects

D L Shapiro

Publications and source records attributed to D L Shapiro.

At least 55 records · Page 3Linked to original sources
PubMed1985

Double-blind, randomized trial of a calf lung surfactant extract administered at birth to very premature infants for prevention of respiratory distress syndrome.

Organic solvent extraction of surfactant obtained by lavage of calf lungs yields a highly surface-active material. A double blind, randomized clinical trial to determine the effect of this material on respiratory distress syndrome in premature infants was initiated in the Neonatal Intensive Care Unit at the University of Rochester in December 1983. Infants 25 to 29 weeks gestational age were eligible for entry into the trial. At the time of this interim analysis 32 patients had been randomly selected and entered into the trial, 16 surfactant-treated patients and 16 in a control group who received only saline. At birth, intrapulmonary instillation of the calf lung surfactant extract dispersed in saline or saline alone occurred in the delivery room immediately after intubation and prior to ventilation; infants were then ventilated and treated as usual. At 6, 12, 24, 48, and 72 hours after birth, the severity of respiratory distress was categorized as either minimal, intermediate, or severe based on oxygen and mean airway pressure requirements. Differences observed at six hours after birth were of marginal significance, but at 12 and 24 hours the surfactant-treated group had significantly (P less than .01) less severe respiratory distress compared with the control group. Differences between treated and control infants were not statistically significant at 48 and 72 hours after birth. In four surfactant-treated infants the severity of respiratory distress worsened between 24 and 48 hours after birth, suggesting that one dose of surfactant at birth may not be sufficient for some infants.

Clinical Trials as Topic↗
PubMed1984

Radiation induced secretion of surfactant from cell cultures of type II pneumocytes: an in vitro model of radiation toxicity.

The pathogenesis of pneumonitis and fibrosis secondary to lung irradiation is incompletely understood. The role of the type II alveolar epithelial pneumocyte in these processes has been under investigation. The type II pneumocyte has been shown in vivo to respond to radiation induced injury with release of pulmonary surfactant. The effect of irradiation on cell cultures of type II pneumocytes was studied to determine if this could be reproduced in vitro. Type II pneumocytes were found to release surfactant material with a threshold of radiation dose between 1000 and 1500 rad. This is similar to the dosage range over which the same effect has been demonstrated in vivo. Experimental results support the concept that the release of surfactant is not due to either cell disruption or non-specific release of phospholipid from cell membranes. Irradiation appears to trigger membrane receptor mediated surfactant release. In addition, irradiation abolishes the ability of cells to subsequently respond to a physiologic agonist, suggesting radiation induced damage to the secretory mechanism. These studies establish that surfactant release in response to irradiation in vivo is a direct effect on type II pneumocytes. Cell cultures of type II pneumocytes can serve as a laboratory model of lung cell radiation toxicity.

Animals↗
PubMed1984

Monoclonal antibodies to surface antigens of rabbit type II pneumocytes.

Techniques for the production of monoclonal antibodies to cell surface antigens of type II pneumocytes are reported. Using these techniques, over 200 hybridomas were produced from spleen cell fusions of 8 mice. Of these, 25 expressed activity toward the type II pneumocyte cell surface. Many antibodies cross-reacted with a variety of cells and membranes from other organs and species, suggesting that these antibodies were ubiquitous to membrane antigens. Most of the antibodies cross-reacted strongly with dog lung membranes, suggesting the existence of common mammalian lung determinants. Five hybridomas produced supernatant antibody with considerable specificity for type II pneumocytes. Ascites fluid antibody was produced to these 5 hybridomas. Immunofluorescent staining of type II pneumocyte cell surfaces could be demonstrated with all 5 of these antibodies. This initial study demonstrates the feasibility of producing monoclonal antibodies to cell surface antigens of the type II pneumocyte.

Animals↗
PubMed1984

Job satisfaction and stress among neonatologists.

Neonatology is reputed to be a stressful pediatric subspecialty. To quantify objectively this stress and to assess the factors involved, a questionnaire was mailed to neonatologists in the northeastern United States. Ninety-six (70%) replied. A five-point scale was used to determine the level of satisfaction with neonatology as a career and the level and type of stress experienced at work. Almost all neonatologists experienced stress at work: 34% moderately severe and 16% very severe stress. Open-ended questions indicated that the major causes of stress were excessive work load, eg, on call too often or calls at night; problems in patient care, especially dealing with infant death; and staff disagreements, especially nurse or housestaff conflicts. Twenty percent of those surveyed suffered a stress-related illness in the previous 5 years. One sixth of the neonatologists were either moderately or very dissatisfied with their career. Major dissatisfactions were: too much work, especially managing many sick patients; lack of resources, including inadequate salary; too much stress at work; and administrative demands. Job satisfaction was derived from patient care, teaching, intellectual stimulation, and research. Altering subspecialty had been considered at some time by 58% (15% very seriously). This study confirms that neonatology, in the eyes of those who practice it, is a highly stressful career. It also suggests that job stress is a greater problem than job dissatisfaction.

Adult↗
PubMed1983

Properties of freshly isolated type II alveolar epithelial cells.

The biochemical characteristics of type II alveolar epithelial cells dissociated from adult rabbit lung by instillation of low concentrations of an elastase trypsin mixture are reported. Cells studied immediately (within 4 h) after isolation were found to incorporate the radioactively labelled precursors [U-14C]glucose, [methyl-3H]choline and [3H]palmitate into cellular phosphatidylcholine at rates 2-10-fold higher than previously reported for cells not subject to short-term cell culture. Secretion of phosphatidylcholine was stimulated by beta-adrenergic agonists. Measurement of specific activities of enzymes of phospholipid biosynthesis in subcellular fractions of isolated lung cells showed a significant enrichment of acyl coenzyme A-lysophosphatidylcholine acyltransferase, an enzyme believed to be involved in pulmonary surfactant phosphatidylcholine remodeling, in the endoplasmic reticulum of type II cells. These observations support the utility of freshly isolated type II cells as a model system for the study of the functions of the alveolar epithelium.

Animals↗
PubMed1983

Surfactant release as an early measure of radiation pneumonitis.

The immediate release of surfactant into lung alveoli following irradiation has been studied as a potential indicator for the later development of radiation pneumonitis. Utilizing single dose radiation exposure to the whole thorax in male LAF1/J mice, steep dose response curves for lavaged alveolar surfactant were identified at 7 and 28 days after exposure. Seven days after irradiation there was no elevation with doses up to and including 12 Gy; above this dose a detectable increase occurred. At 28 days the surfactant recovered by lavage was elevated compared to the levels seen at day 7 for all doses; doses greater than 12 Gy produced surfactant values significantly greater than those found in mice treated with 12 Gy or less. The radiation pulmonary lethality dose response curve assessed four months later indicated an LD50 value of approximately 13 Gy. The early biochemical effect and the later radiation pneumonitis lethalities therefore closely coincided. The evidence strongly indicates that alveolar surfactant release uncovered hours to days after radiation exposure may be an early biochemical marker that predicts for subsequent pneumonitis radiation injury.

Animals↗
PubMed1983

Natural and artificial lung surfactant replacement therapy in premature lambs.

The effect of tracheal instillation of surface-active mixtures in premature lambs was studied as an animal model of exogenous surfactant replacement therapy for the respiratory distress syndrome (RDS). Specific mixtures studied were 7:3 (molar ratio) dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylglycerol (PG) and extracted mixed lipids (with 1% protein) from cow lung lavage (CLL). Preventilatory tracheal instillation of greater than 15 mg/kg of CLL in 10 ml 0.15 M NaCl to premature lambs gave improved alveolar-arterial O2 gradient and blood gases and increased lung compliance, compared with control lambs over a 15-h period. Lambs receiving 7:3 DPPC:PG dispersions were not improved over controls with regard to pressure-volume characteristics and were worse than controls in arterial oxygenation. In terms of in vitro surface properties, both extracted natural CLL and 7:3 DPPC:egg PG were able to lower aqueous surface tension to 1 dyn/cm under dynamic compression. However, the dynamic respreading of CLL films on successive surface cycles was superior to that of 7:3 DPPC:PG. Moreover, after dispersal in 0.15 M NaCl by vortexing (5 mg/80 ml), CLL adsorbed to surface pressure (tau values of 45 dyn/cm within 10 min. 7:3 DPPC:PG adsorbed to significantly lower tau values after subphase dispersal by a variety of methods.

Animals↗
PubMed1983

Effects of dexamethasone on beta-adrenergic receptors in fetal lung explants.

The action of beta-adrenergic agonists on pulmonary surfactant secretion requires lung cell membrane beta-adrenergic receptors. In the fetus, the density of beta-adrenergic receptors in lung increases in the latter stages of gestation. The increase in density can also be induced by maternal glucocorticoid treatment. In this study, we measured beta-adrenergic receptors in developing rat lung by (-) [3H]-dehydroalprenalol (DHA) binding and confirmed the increase in beta-adrenergic receptors late in gestation. To determine if glucocorticoids have a direct effect on fetal lung to regulate beta-adrenergic receptors, we cultured fetal lung explants with dexamethasone. Treated explants had increased DHA binding compared with controls (138.0 +/- 8.8 versus 63.2 +/- 5.0 fmole/mg membrane protein). Scatchard analysis revealed that the increased DHA binding was due to an increase in maximum receptor number. There was also a significant difference in the dissociation constant of the treated and control explants (0.85 +/- 0.07 nM versus 0.43 +/- 0.08 nM, respectively; P less than 0.05), suggesting that the receptors induced by dexamethasone were of lower binding affinity. Cyclohexamide, an inhibitor of protein synthesis, completely eliminated the dexamethasone induced increase in DHA binding. These data indicate that glucocorticoids have a direct effect on fetal lung to increase beta-adrenergic receptor density and that new protein synthesis is required for this effect.

Alprenolol↗
PubMed1982

Sequential effects of irradiation on the pulmonary surfactant system.

This study examines the effect of irradiation on lung surfactant synthesis and secretion in mice. Animals were irradiated with 650, 1300, or 1950 rad and morphological and biochemical indices of surfactant system function were followed for 18 weeks. No changes were seen at 650 rad; the results at 1300 and 1950 rad were virtually identical. Increased amounts of alveolar surfactant phospholipid were measureable by 24-hours. This persisted for four weeks and returned to normal by 18 weeks. Tissue surfactant phospholipid was initially reduced, returned to normal by four weeks and was increased at 18 weeks. At 18 weeks there was increased incorporation of surfactant precursor and increased production of alveolar surfactant. These biochemical changes were reflected in morphologic alterations showing release of lamellar body contents into alveoli in the first week and an increase in lamellar bodies in type II pneumocytes by 18 weeks. Elevated tissue protein levels and morphologic evidence of increased collagen formation were also found at 18 weeks. These findings indicate effects of irradiation on the pulmonary surfactant system and have important implications for the pathogenesis and potential therapy of radiation pneumonitis.

Animals↗
PubMed1982

Concurrent outbreaks of rhinovirus and respiratory syncytial virus in an intensive care nursery: epidemiology and associated risk factors.

An outbreak of viral respiratory disease occurred in eight infants in a neonatal intensive care unit during the 1980 winter respiratory season. Four infections with respiratory syncytial virus and four infections with rhinovirus were identified. Epidemiologic investigation revealed that viral respiratory infection was significantly associated with intubation with orotracheal tubes (P = 0.001), with the presence of both a nasal feeding tube plus an orotracheal tube together (P = 0.007), and with assisted ventilation (P = 0.009) when compared to uninfected controls. Twenty-seven of 85 (30.6%) personnel working in the unit at the time of the outbreak reported a history of upper respiratory illness during the week prior to the outbreak, and 46 (54.1%) of them had had contact with patients in areas of the hospital where patients infected with RSV and rhinovirus were housed. The data suggest that both viruses were transmitted to the babies by hospital personnel. Rhinoviruses can be nosocomial pathogen in neonates with compromised pulmonary function, and the clinical presentation of rhinovirus infection in neonates may be difficult to distinguish from that produced by RSV.

Cross Infection↗
PubMed1982

Isolation of type II pneumocytes by laser flow cytometry.

The isolation of a pure population of type II pneumocytes from adult rabbit lung by the technique of multiparameter laser flow cytometry is reported here. Lipophilic phosphine-3R was used to stain cell dissociated from lungs by elastase and trypsin. Type II cells were then sorted by simultaneous measurement of high phosphine-3R fluorescent staining of lamellar bodies and intermediate intensity of low-angle light scatter. We were able to obtain an essentially pure population (98%) at sorting rates of 5 X 10(5) lamellar-body-containing cells per hour. The cell sorter technique offers an attractive alternative to the density gradient isolation of type II cells, particularly in terms of detailed population analysis. In addition, refinements in cell sorter methods offer the potential to discriminate differentiating type II cells with few lamellar bodies that do not segregate on the basis of buoyant density.

Acridines↗
PubMed1982

Bilirubin interactions with phospholipid components of lung surfactant.

This work examines the dynamic surface pressure-area behavior of films of unconjugated bilirubin spread from chloroform solution at 22 degrees C on 0.15 M NaCl and buffered phosphate subphases. Film behavior is examined at pH 5.5, 7.4 and 8.0. The interactions of bilirubin in mixed films with dipalmitoyl phosphatidylcholine and with 9:1 dipalmitoyl phosphatidylcholine:dioleolyl phosphatidylcholine are examined at similar temperature and pH values. It is found that unconjugated bilirubin modifies the dynamic surface pressure-area behavior of phospholipid films in both the high and low surface pressure regimes, with bilirubin exerting its greatest effect at low pH where its subphase solubility is low. Because many premature infants suffering from the Respiratory Distress Syndrome (RDS) have accompanying hyperbilirubinemia, with possible bilirubin transport to the alveolar space, the interactions of bilirubin with phospholipid films are discussed in terms of potential effects on pulmonary surfactant in vivo.

Bilirubin↗
PubMed1982

Effects of maternal ritodrine therapy on fetal rat brain development.

The effects of maternal treatment with ritodrine, a beta 2-adrenergic agonist, on the biochemical development of fetal brain were studied in an animal model. Pregnant rats were treated with long and short dosage schedules. Fetuses were delivered by hysterotomy 4 h after the last dose. No differences in the fetal brain content of protein, DNA, glycogen, cholesterol or beta-adrenergic receptors were found. In this animal model, using relatively high maternal doses of ritodrine, there were no apparent effects on the fetal brain biochemical indices measured, suggesting a relatively high efficacy to toxicity ratio of ritodrine for brain development.

Animals↗
PubMed1982

Morphologic changes reflecting early and late effects of irradiation of the distal lung of the mouse: a review.

In radiation of the thorax, the lung has been shown to be a major dose-limiting organ. The early and late responses of the lung to radiation has been reviewed, with primary emphasis on the following cell types: type II pneumocyte, type I pneumocyte, pulmonary endothelial cell and macrophage. The earliest observable and quantifiable cellular response to radiation is exhibited by the type II pneumocytes as a decrease in lamellar bodies and a corresponding increase in surfactant content of the alveolar lavage. By 18-63 weeks following exposure, several type II cells, restored in their lamellar body population, undergo degeneration and sloughing into alveolar spaces. Type I pneumocytes generally exhibit little change, although some investigators describe alveolar denudation due to degenerating type I cells. Macrophages decrease in numbers following irradiation, returning to normal populations by 4 weeks. These changes correspond closely to the changes in alveolar lavage phospholipid phosphorus. Descriptions of radiation-induced damage to endothelial cells are variable. However, blebbing and vacuolation appear to be late developing responses, although altered permeability may be earlier in its expression. Radiation pneumonitis and fibrosis are the two major clinical and experimental responses of the lung to radiation following exposures of greater than 12 Gy. The former appears to involve type II cells, macrophages and pulmonary endothelial cells, and for the latter macrophages, fibroblasts, type II pneumocytes and the pulmonary endothelial cells are involved. The two events are not interdependent, and may not necessarily be interrelated.

Animals↗
PubMed1981

Early closure of the patent ductus arteriosus in very low-birth-weight infants: a controlled trial.

A controlled clinical trial comparing early closure (mean = 48.8 hours) of the patent ductus arteriosus using indomethacin to conventional medical management, with intervention only after cardiopulmonary decompensation (mean = 167.4 hours), was undertaken in 24 preterm infants with severe respiratory distress syndrome and evidence of PDA. An interval analysis of one-half the projected sample revealed that infants undergoing early closure of the PDA had significantly reduced occurrence of BPD or mortality by 6 months of age. A comparison of birth weight, Apgar scores, gestational age, age of initial PDA diagnosis, and fluid therapy during the first seven days of life showed no significant differences between early intervention and control groups. At the time of the interval analysis, there were no differences between the groups in duration of intermittent mandatory ventilation or oxygen exposure. Studies will be required to determine whether these and other variables can be altered by early closure of the PDA.

Bronchial Diseases↗