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Biomedical subjects

D L Shapiro

Publications and source records attributed to D L Shapiro.

At least 19 recordsLinked to original sources

Selection based on merit versus demography: implications across race and gender lines.

In a replication and extension of the study by M. E. Heilman, M. C. Simon, and D. P. Repper (1987), 201 undergraduates participated in a simulation in which they experienced differing selection procedures and outcome feedback. Selection procedures did not have the deleterious effects on women that were found previously. Instead, race interacted with gender to moderate this relationship, and outcome played a significant role in participant self-evaluations. Black participants rated their leadership ability highest when both chosen preferentially and given negative outcome feedback, apparently because of a desire to maintain positive self-esteem. The latter explanation was supported in a follow-up study in which undergraduates (n = 80) worked in groups and received negative outcome feedback from either a racially similar or racially different experimenter. Theoretical and practical implications relating to diversity and self-appraisal management are discussed.

Black or African American↗

Adolescent survivors of childhood sexual abuse: the mediating role of attachment style and coping in psychological and interpersonal functioning.

OBJECTIVE: To examine attachment style and coping strategies as potential mediating variables between childhood sexual abuse (CSA) and psychological and interpersonal functioning in an attempt to explain variability in extent of disorder and level of functioning. METHOD: Eighty adolescent females, aged 14-16 years, answered questions regarding abuse history, attachment style, coping with an interpersonal stressor, depression and trauma symptomatology, and conflict with a best friend. RESULTS: Structural equation modeling analyses indicated that attachment style mediates the effects of CSA and child abuse and neglect on coping and psychological distress. The indirect effects of CSA and other abuse through attachment accounted for most of the effects on coping and psychological distress. Avoidant and cognitive coping strategies also served as mediators in the models, accounting for most of the effects of the other variables on interpersonal conflict. CONCLUSIONS: The findings indicate that attachment style and coping strategies influence psychological and interpersonal functioning, mediating the direct effects of CSA and other types of child abuse and neglect. These results have implications for therapeutic intervention with children and adolescents who have experienced child abuse.

Adaptation, Psychological↗

Treatment of HIV associated psoriatic arthritis with oral gold.

We report a patient with human immunodeficiency virus (HIV) infection and disabling psoriatic arthritis who was treated with auranofin. Her skin lesions and arthritis resolved after auranofin treatment and she has remained free of opportunistic infections during 24 mo followup. Her CD4 count during oral gold therapy showed a significant, sustained increase in CD4 cells. The literature on the effect of gold compounds on HIV infectivity and HIV reverse transcriptase is reviewed.

Adult↗

Regression of the nephrotic syndrome in rheumatoid arthritis and amyloidosis treated with azathioprine. A case report.

Secondary or reactive (AA) amyloidosis is a well-known complication of certain rheumatic diseases, particularly rheumatoid arthritis (RA). This case report describes a patient with RA complicated by amyloidosis and the nephrotic syndrome, which regressed after treatment with azathioprine. The AA amyloidosis was documented by renal and lymph node biopsies and by the presence of proteinuria. Evaluation for other etiologies of proteinuria was negative. After treatment with azathioprine, the proteinuria resolved and the serum albumin level increased from 1.9 mg/dl to normal. This is the first published report of azathioprine therapy resulting in a reversal of the nephrotic syndrome in a patient with RA and secondary amyloidosis.

Amyloidosis↗

Independent evolutionary origin of histone H3.3-like variants of animals and Tetrahymena.

All three genes encoding histone H3 proteins were cloned and sequenced from Tetrahymena thermophila. Two of these genes encode a major H3 protein identical to that of T. pyriformis and 87% identical to the major H3 of vertebrates. The third gene encodes hv2, a quantitatively minor replication independent (replacement) variant. The sequence of hv2 is only 85% identical to the animal replacement variant H3.3 and is the most divergent H3 replacement variant described. Phylogenetic analysis of 73 H3 protein sequences suggests that hv2, H3.3, and the plant replacement variant H3.III evolved independently, and that H3.3 is not the ancestral H3 gene, as was previously suggested (Wells, D., Bains, W., and Kedes, L. 1986, J. Mol. Evol., 23: 224-241). These results suggest it is the replication independence and not the particular protein sequence that is important in the function of H3 replacement variants.

Amino Acid Sequence↗

Surfactant replacement therapy in respiratory distress syndrome. Meta-analysis of clinical trials of single-dose surfactant extracts.

Replacement therapy with surfactant extracts in premature infants with respiratory distress syndrome has been evaluated in several clinical trials. The results of individual trials do not provide conclusive evidence that administration of a single dose of surfactant improves morbidity or mortality. Meta-analysis is a statistical method to combine the results of such clinical trials, and combined analysis provides a means to overcome the problem of not being able to detect significant small differences in individual trials due to these small sample sizes. Seven clinical trials (277 patients treated with nonhuman surfactant extract and 263 controls) met the criteria for analysis; five outcome measurements (mortality, patent ductus arteriosus, pneumothorax, intraventricular hemorrhage, and bronchopulmonary dysplasia) were selected to estimate the treatment effect. The meta-analysis showed that a single dose of surfactant administered before the first breath or within 15 hours of birth significantly decreased the mortality rate (95% confidence interval = -0.19 to -0.03) and the risk of developing pneumothorax (95% confidence interval = -0.28 to 0.14) in infants with respiratory distress syndrome. Further clinical trials are needed to evaluate other aspects of surfactant replacement therapy in premature infants because inconsistent results were observed among the seven analyzed studies.

Confidence Intervals↗

Surfactant treatment of full-term newborns with respiratory failure.

Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns. Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses. The group mean fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O. Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01 before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours. The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/- 1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6 hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Changes in gene expression in hyperoxia-induced neonatal lung injury.

Exposure to high concentrations of oxygen (hyperoxia) can result in lung injury. The biochemical basis of this injury is poorly understood, but it is likely to include alterations in gene expression. Hyperoxia-induced (H-I) cDNAs have been molecularly cloned (Horowitz et al. J. Biol. Chem. 264: 7092-7095, 1989) from the lungs of an adult rabbit exposed to toxic levels of oxygen. One of them (H-I 1) was identified as encoding the tissue inhibitor of metalloproteinases (TIMP), a key regulatory protein of extracellular matrix turnover. Here we identify another clone (H-I 3) as encoding pulmonary surfactant apoprotein A (SP-A). We also show that in neonatal rabbits exposed to 100% oxygen for 96 h, the mRNAs corresponding to TIMP, SP-A, and another H-I gene are increased. These studies have begun to explore specific changes in gene expression associated with neonatal hyperoxic lung injury.

Animals↗

Surfactant apoprotein A (SP-A) is synthesized in airway cells.

The pulmonary surfactant apoproteins A, B, and C (SP-A, SP-B, and SP-C, respectively) function in concert with surfactant phospholipids to reduce surface pressure in the alveolus. Surfactant apoproteins also regulate surfactant synthesis, secretion, adsorption, and recycling. SP-A and B have been localized by immunocytochemistry to alveolar epithelial (type II) cells, alveolar macrophages, and nonciliated bronchiolar epithelial (Clara) cells. In contrast, in situ hybridization to SP-A and B mRNA in human lung has shown SP-A and B transcripts in type II cells, but only SP-B message in Clara cells, implying that synthesis of SP-A occurs exclusively in type II cells. In this report, in situ hybridization to SP-A mRNA was performed on adult and developing rabbit lung and on human lung. SP-A transcripts were found in type II cells and bronchiolar epithelium of both species. The distribution of SP-A message-containing cells in the bronchiolar epithelium of rabbits and humans was similar to the distribution of Clara cells in these two species. These data indicate that SP-A is not only synthesized in type II cells but also in Clara cells.

Animals↗

The role of the lumbar puncture in the admission sepsis evaluation of the premature infant.

Premature infants with respiratory distress commonly receive evaluation for sepsis, including a lumbar puncture, within a short time after admission to a neonatal intensive care unit. We questioned the use of the lumbar puncture during the early sepsis evaluation, and since 1979, have omitted this procedure as part of the initial evaluation for sepsis (within 6 hours of birth) of premature infants. We monitored this policy to detect any change in the incidence of meningitis, and now report results accumulated over a 7-year period. From 1979 to 1986, 1390 inborn premature infants of 34 weeks' gestation or less were evaluated for early sepsis within 6 hours of birth. Thirty-two infants (2.3%) were diagnosed with sepsis. Fifteen of these infants died in the first 24 hours of life. Meningitis was not demonstrated by autopsy evaluation. The surviving 17 infants diagnosed with sepsis did not have meningitis. One hundred twenty-three infants whose initial blood cultures were negative developed infection later in their hospital course. Eleven of these 123 infants had infections with perinatally acquired organisms; two had group B streptococcus (GBS) meningitis. Their cases were not compatible with missed meningitis. The remaining 112 infants developed nosocomial infections of which 38.3% developed meningitis without associated bacteremia. These results suggest that the omission of the lumbar puncture in the early sepsis evaluation of the premature infant did not result in any missed meningitis and spared many infants the procedure shortly after birth. The lumbar puncture, however, continues to be vital in the assessment of late infections of the neonate.

Bacteria↗

Hyperoxic exposure alters gene expression in the lung. Induction of the tissue inhibitor of metalloproteinases mRNA and other mRNAs.

Exposure to high concentrations of oxygen can result in tissue damage, particularly in the lung. Lung pathology induced by hyperoxia includes changes in lung cell populations and morphology. Presumably, alterations in gene expression underlie some of these cellular changes. In order to better understand the molecular basis of these events, a cDNA library was constructed from the mRNA of the lungs of a hyperoxia-exposed rabbit and differentially screened for clones corresponding to hyperoxia-induced messages. This approach has led to the isolation of four clones, three of which are presented in this communication. One clone corresponds to a message whose steady state levels were induced 6-fold and encodes the tissue inhibitor of metalloproteinases, a protein that plays a key role in the regulation of connective tissue turnover in some cells and potentiates erythroid development in others.

Amino Acid Sequence↗

Fiberoptic bronchoscopy in the treatment of intubated neonates.

A study of the role of fiberoptic bronchoscopy in intubated neonates was conducted. The study aimed to ascertain the applicability of fiberoptic bronchoscopy for assessment of endotracheal tube tip position, and to assess the incidence and clinical significance of airway disease in unselected patients. Seventy examinations on 65 neonates were performed without interruption of mechanical ventilation. The procedure was well tolerated in all cases. The accuracy of bronchoscopic measurement of endotracheal tube tip position improved markedly with user experience and reached a correlation of .96 with a chest roentgenogram. Although the technique was safe and accurate, the need for available and skilled personnel may limit the applicability of this method for endotracheal tube tip position assessment. Significant airway disease requiring a change in treatment was found in 13 patients (19%). This high incidence of significant but clinically unsuspected airway disease suggests that there should be more frequent consideration of diagnostic bronchoscopy in all sick intubated neonates who are at risk for airway disease.

Airway Obstruction↗

Isolation of alveolar epithelial cells from lung tissue obtained at autopsy.

Lung alveolar epithelial cells have been studied in a variety of laboratory animal models, and studies of human alveolar epithelial cells are important for comparison to information obtained from animal studies. Autopsy material is a source of human cells for study. Studies of human autopsy material revealed variables that negatively affected the yield of viable cells. For specimens from adults, these included death greater than 12 h before cell isolation, obvious severe lung fibrosis, longstanding metabolic disorders, and lung congestion indicated by weight of the right middle lobe greater than 150 g. Samples from children yielded significant numbers of viable cells up to 18 h after death. For 17 specimens that conformed to the above criteria, approximately 8.5 x 10(6) alveolar cells were obtained per gram of tissue (tissue weights ranged from 30 to 108 g) using a procedure involving instillation of proteases into the airways. The cells could be further fractionated, and 10 to 15% of the mixed cells obtained were type II pneumocytes. Analysis of NADPH cytochrome-c-reductase distribution in subcellular fractions provided evidence that the cells obtained were intact. Phospholipid enzyme activities and synthetic activity were within the ranges previously found in laboratory studies of freshly obtained animal lungs. These results suggest that significant numbers of viable and functional human lung cells, including type II pneumocytes, can be obtained from autopsy material.

Animals↗

Serum markers for prediction of pulmonary radiation syndromes. Part I: Surfactant apoprotein.

Detection of a biochemical marker indicating radiation lung injury prior to the onset of clinical pathologic events could prove valuable in patient management. An increased level of alveolar surfactant is one of the earliest detectable changes following lung irradiation, starting within hours of irradiation and persisting a maximum of 2-6 weeks. However, because broncho-alveolar lavage is impracticable and endothelial cell damage due to radiation results in changes in permeability of vessel wall with leakage of alveolar proteins into serum, identification of serum markers was sought. A series of experiments in rabbits are described that clearly demonstrate serum surfactant apoprotein is an accurate marker and predictor for later lethal radiation pneumonitis. At 3-7 days after graded single doses to lung, surfactant was found in the serum paralleling the dose response for lethality. Control studies with a physiologic agent such as terbutaline release alveolar surfactant, but no serum surfactant was detected. Monitoring serum surfactant could direct preventive intervention prior to clinicopathologic manifestation of pulmonary radiation syndromes.

Animals↗

Lung injury in the neonatal piglet caused by hyperoxia and mechanical ventilation.

Neonatal lung injury from hyperoxia and mechanical hyperventilation was studied in newborn piglets hyperventilated (arterial PCO2 15-20 Torr) for 24-48 h with 100% O2 and compared with unventilated controls. Pulmonary function testing was performed, and biochemical indicators of lung injury were analyzed from tracheobronchial aspirates at 0, 24, and 48 h. Lung sections were obtained for light and electron microscopy, and bronchoalveolar lavage fluid was analyzed for surfactant composition and activity. At 24 h significant changes in tracheobronchial aspirate albumin concentrations (up 78%) and percent of polymorphonuclear cells (up 16%) were demonstrated. At 48 h a 35% decrease in dynamic lung compliance (P less than 0.05) and a 36% increase in pulmonary resistance (P less than 0.05) were noted. Further biochemical abnormalities occurred with total cell counts increased by 271% (P less than 0.02), albumin 163% (P less than 0.05), total protein 217% (P less than 0.01), and elastase 108% (P less than 0.02). Pathological analyses revealed mild lung injury at 24 h and marked inflammation, abnormal inflation patterns, flattening of Clara cells, fibrinous exudate and edema, early collagen formation, and cell necrosis observed at 48 h. Bronchoalveolar lavage surfactant had normal biophysical activity. Results demonstrate that exposure of neonatal piglets to O2 and mechanical hyperventilation for 48 h cause severe progressive lung injury.

Animals↗

Membrane phospholipid methylation is associated with surfactant secretion in rabbit type II alveolar epithelial cells.

We investigated the involvement of membrane phospholipid methylation in receptor-mediated secretion of surfactant in adult rabbit type II alveolar epithelial cells (type II pneumocyte). Phospholipid methyltransferase activity was found in type II pneumocyte microsomes. Cell cultures of adult rabbit type II pneumocytes were then used to assay methyltransferase activity in the presence of the beta-adrenergic agonist, terbutaline, and the methyltransferase inhibitor, 3-deazaadenosine. Terbutaline predictably stimulated adenylate cyclase activity and surfactant secretion. It was also found to stimulate incorporation of methyl groups into phosphatidylcholine and to increase beta-adrenergic receptor availability as assayed by binding of dihydroalprenolol (DHA). Surfactant secretion, as well as adenylate cyclase activity, were stimulated by terbutaline and were inhibited by 3-deazaadenosine. 3-Deazaadenosine did not inhibit DHA binding. These results suggest that phospholipid methylation plays a role in stimulus-secretion coupling in adult rabbit type II pneumocytes.

Adenylyl Cyclases↗

Decreased cholestasis with enteral instead of intravenous protein in the very low-birth-weight infant.

Thirty to 50% of very low-birth-weight infants have parenteral nutrition-associated cholestasis. To test the hypothesis that the incidence of cholestasis would be decreased if parenteral amino acids were avoided and protein given enterally, infants with a gestational age of less than 30 weeks were randomized to two groups. One group received amino acid-free parenteral nutrition and whey protein enterally with added premature infant formula. The control group received standard parenteral nutrition with amino acids and enteral premature formula. At the end of 3 weeks of parenteral nutrition, infants who had a direct serum bilirubin level of greater than 3 mg/dl were considered to have significant cholestasis. Twenty-nine infants required parenteral nutrition for 3 weeks, 17 in the whey group and 12 in the control group. No instances of significant cholestasis were observed in the whey group (0/17), whereas seven of 12 infants (58%) in the amino acid control group had cholestasis (p less than 0.001).

Amino Acids↗

Surfactant replacement therapy: impact on hospital charges for premature infants with respiratory distress syndrome.

Surfactant replacement therapy for neonatal respiratory distress syndrome has the potential to reduce morbidity and mortality of very premature infants. To investigate whether surfactant replacement therapy will also reduce hospital charges for these infants, we compared the hospital charges incurred by a group of patients treated with surfactant with charges of control patients. Mortality in the surfactant-treated group (8%) was significantly decreased compared with the control patients (29%). Average daily hospital charges in the surfactant-treated patients were 25% less than for the control patients. Most of the savings in daily hospital charges were due to a 52% reduction in daily charges for laboratory, x-ray, respiratory therapy, and other ancillary services. Similarly, ancillary charges for the first full week of hospitalization were significantly reduced by $1,883 for patients who received surfactant therapy. Analysis of the charges for the entire hospitalization revealed that surfactant-treated patients had a significantly smaller proportion of their charges that resulted from ancillary services and an increased proportion due to room charges. The average total hospital charges for the two groups were similar, but the total hospital charges to produce a surviving infant were $18,500 less in the surfactant-treated group than the charges to produce a survivor from the control group. It is likely that, in addition to a reduction in neonatal mortality and morbidity from respiratory distress syndrome, surfactant replacement therapy may also significantly reduce charges for ancillary services for these patients. In this way, surfactant therapy may be cost-effective by improving survival without increasing overall hospital costs.

Economics, Hospital↗