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Biomedical subjects

M Hallman

Publications and source records attributed to M Hallman.

At least 109 records · Page 6Linked to original sources

Immunogenicity of surfactant. II. Porcine and bovine surfactants.

Protein-containing surfactants of human and animal origin are being used increasingly to treat neonatal and adult respiratory distress syndromes. This trend led us to examine the antigenicity of two important preparations of animal surfactant, cow lung surfactant extract (CLSE) and a porcine surfactant preparation, Curosurf. We describe here 15 monoclonal antibodies against Curosurf and four against CLSE. Antibodies were studied by Western blot analysis to determine their ability to recognize protein components of their respective surfactant preparations. They were also tested for their ability to inactivate surfactant in vitro, assayed using the pulsating bubble surfactometer. Several antibodies directed against CLSE or Curosurf functionally inactivate the surfactant to which they were raised. We determined the degree of immunologic cross-reactivity between antibodies directed to CLSE and Curosurf against the other surfactant and also against human surfactant, both by Western blot and by examining functional inactivation in vitro. Antibodies to these animal surfactants that are commonly used therapeutically may inactivate the specific animal surfactant to which they were raised, as well as human and other surfactants. Generally, when antibodies inactivate surfactant from more than one animal species, they inactivate heterologous surfactants comparably to the extent to which they inactivate the surfactant to which they are directed. Immune complexes between anti-surfactant antibodies and surfactant have been described in the course of neonatal respiratory distress syndrome. The potential pathophysiological importance of anti-surfactant antibodies may therefore lie in their ability to inactivate administered surfactant, other similar surfactants and endogenous surfactant. In so doing, these antibodies may potentiate surfactant deficiency or pulmonary injury initiated by other stimuli.

Animals↗

Lung surfactant in respiratory distress syndrome.

Severe respiratory failure is always associated with a defect in the surfactant system. Surfactant substitution in newborn infants with respiratory distress syndrome (RDS) has gained worldwide acceptance. In the present study, we have evaluated whether surfactant diagnostics are of use in choosing recipients of exogenous surfactant. In addition, we studied whether factors apparently unrelated to surfactant influence the degree of respiratory failure and surfactant responsiveness. In small preterm infants, the surfactant indices in amniotic fluid (L/S ratio and phosphatidylglycerol), within 3 days of birth, predicted the risk of RDS with a sensitivity of 90-100%, and a specificity of 50-85%. The surfactant indices, measured in BAL, predicted the risk of ARDS (which became evident 1 to 7 days later) with a sensitivity of 50-60% and a specificity of 59-65%. In small preterm infants with RDS, the amount of fluids given during the first day correlated positively with the degree of respiratory failure and negatively with the degree of surfactant responsiveness. According to an experimental study, in hydrostatic lung edema, exogenous surfactant is diluted by edema fluid and becomes sensitive to inhibitors of surfactant function. Beside dosage, quality, and time of administration, the management of patients largely dictates the responsiveness to exogenous surfactant.

Humans↗

Perinatal development of inositol synthesis and catabolism in rabbit kidney.

Inositol influences growth and perinatal development. To investigate the causes of the decrease in serum inositol levels during perinatal development, the rate-limiting enzyme activities in the catabolism and synthesis of inositol, inositol oxygenase and glucose-6-phosphate:L-inositol-1-phosphate cyclase (cyclase) were measured. The specific activity of inositol oxygenase (uniquely present in the kidney) increased 18-fold between the 25th fetal and the 17th neonatal days, and, at the same time, the specific activity of cyclase decreased by 50%. Between cortex and medulla, there were striking differences in the distribution of inositol oxygenase, when compared to the distribution of both cyclase and free inositol. Inositol supplementation during pregnancy increased serum inositol both in the doe and the fetuses, and tended to increase the inositol concentration in organs with relatively low cyclase activity and low free inositol (liver, lung). An acute oral inositol load and/or glucocorticoid intramuscularly is administered to the pregnant doe did not alter either maternal or fetal inositol oxygenase activities. It is proposed that the tissue contents of inositol are in part regulated by the rate of the endogenous synthesis. The development of inositol oxygenase activity may influence serum inositol concentrations during the perinatal period, in addition to the diet.

Aging↗

Surfactant protein A, phosphatidylcholine, and surfactant inhibitors in epithelial lining fluid. Correlation with surface activity, severity of respiratory distress syndrome, and outcome in small premature infants.

Although surfactant deficiency at birth is the major cause of respiratory distress syndrome (RDS), there is insufficient data on surfactant and surfactant inhibitors after birth. In the present study, a total of 345 airway specimens (AS) from 61 neonates of gestational age of 24 to 29 wk (54 with RDS) were analyzed for concentrations of phosphatidylcholine (PC), saturated PC (SPC), surfactant protein A (SP-A), nonsedimentable protein, and free amino acids in epithelial lining fluid (ELF). The relationship between surfactant indices, surface activity, and severity of RDS was studied. Treatment with human surfactant containing SP-A increased [PC]ELF and [SPC]ELF to levels found in infants without RDS. In placebo-treated infants similar concentrations were first reached between Days 4 and 7. Surfactant treatment increased the low SP-A/SPC ratio, although this ratio remained lower than that in exogenous surfactant. In RDS, the concentrations of free amino acids in ELF were 6 to 31 times higher than in infants without RDS. The nonsedimentable proteins of AS and cationic amino acids increased the minimum surface tension of SP-A-deficient surfactant from AS. Addition of SP-A improved the surface activity. According to multiple regression analysis, In [PC]ELF (p less than 0.0001), SPC/PC ratio (p less than 0.0001), In SP-A/SPC ratio (p less than 0.0002), and [protein]ELF (p less than 0.01) correlated with alveolar-arterial oxygen pressure gradient. Of the infants weighing less than 1,000 g, those who were going to die or develop bronchopulmonary dysplasia had a strikingly lower SP-A/SPC ratio during the first week (less than 25 ng/nmol) than those surviving without BPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Generation of free radicals in lipid emulsion used in parenteral nutrition.

Lipid emulsions used in parenteral nutrition are prone to peroxidation that may be an important feature of oxygen-associated tissue damage. Incubation of lipid emulsion [Intralipid (IL)] with H2O2 and FeCl2 increased lipid peroxidation, measurable as increased production of pentane, from 0.39 +/- 0.33 to 0.99 +/- 0.18 microM (p less than 0.0001). Malondialdehyde was increased from 0.010 +/- 0.005 mM to 0.380 +/- 0.025 mM (p less than 0.001). Superoxide dismutase and catalase (each 100 U/mL) or vitamin C (10 mM) inhibited pentane and malondialdehyde production (p less than 0.0001). Incubation of human erythrocytes in the presence of FeCl2 caused 11.0 +/- 3.2% hemolysis (control 0.95 +/- 0.14%). Addition of 0.44% IL increased hemolysis to 66.5 +/- 3.4%, whereas further addition of vitamin E or C significantly inhibited hemolysis to 16.4 +/- 8.1 and 38.9 +/- 7.1%, respectively (p less than 0.0001). IL was administered i.v. to eight preterm infants. It increased 3- to 28-fold (p less than 0.001) the amount of pentane in expired breath. Partly, this increase was due to pentane dissolved in IL as a result of lipid peroxidation during storage. After discontinuing IL infusion, the elimination of pentane was nonexponential, consisting of a rapid and a slow component. According to our results, IL undergoes peroxidation causing free-radical-dependent damage to human cells. We propose that the adverse effects of parenteral IL are partially caused by free oxygen radicals generated by lipid peroxidation.

Fat Emulsions, Intravenous↗

The use of synthetic peptides in the formation of biophysically and biologically active pulmonary surfactants.

Synthetic pulmonary surfactants consisting of mixtures of phospholipids with synthetic peptides based on the amino acid sequence of human surfactant apoprotein SP-B were prepared. These surfactants were analyzed for their ability to lower surface tension on a pulsating bubble surfactometer and for their capacity to improve lung compliance and increase alveolar expansion in a fetal rabbit model of surfactant deficiency. The data demonstrate that several peptides, ranging from 17 to 45 residues in length, matching the carboxy-terminal sequence of the SP-B protein, when appropriately recombined with the phospholipid dipalmitoylphosphatidylcholine and phosphatidylglycerol (3:1), are capable of producing a synthetic surfactant with biophysical and biologic activity approaching that of human surfactant derived from amniotic fluid.

1,2-Dipalmitoylphosphatidylcholine↗

Factors affecting surfactant responsiveness.

There is a wide variability in the therapeutic responsiveness to exogenous surfactant, a drug that has become generally available for the treatment of lung immaturity and respiratory distress syndrome. Recent studies have demonstrated evidence that therapies decreasing lung edema improve the effectiveness of surfactant substitution. In addition, exogenous surfactant may acutely decrease pulmonary perfusion since the airway pressures are effectively transmitted to airspaces, compressing alveolar capillaries, especially in hypovolemia. Therapies aimed at decreasing lung edema, improving cardiac output, and stepwise weaning from oxygen and ventilatory pressures are cornerstones in the successful management of patients undergoing surfactant therapy.

Ductus Arteriosus, Patent↗

The BPD problem.

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Bronchopulmonary Dysplasia↗

Inositol supplementation in respiratory distress syndrome.

According to preliminary results inositol (INO) is an important nutrient to immature preterm infants (J Pediatr 1987; 110:604). However, it is absent in nutrition of critically ill very low birth weight infants. In a present randomized double blind trial INO or glucose (70-100 mg/kg/day) was given to altogether 230 preterm infants (gestation 24 to 31 w, mean 27.8 w, mean BW 1,106 g) with RDS during 5 neonatal days. Two more courses during the first month were given, if the infant remained respirator-dependent and did not tolerate breast milk. INO-supplemented infants tended to have a milder respiratory course during the first week than those on glucose. The surviving INO-treated infants had a lower incidence of bronchopulmonary dysplasia (BPD) than the controls (p less than 0.01). No infant receiving INO had severe retinopathy (gr 4), whereas of the surviving placebo treated infants 8.8% became blind (p less than 0.005). Inositol promotes endothelial cell growth, enhances glucocorticoid-mediated lung epithelial cell differentiation, and may serve as an antioxidant. INO should be seriously considered as a nutrient during compromised neonatal transition of very low birth weight infants.

Cause of Death↗

Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants.

Lipid peroxidation was measured in 19 very low birth weight infants with respiratory distress syndrome by quantitating ethane and pentane in expired air during the first 5 days postnatally. Despite high levels of inspiratory oxygen, the ethane and pentane output was low within the first 24 hours; thereafter it increased up to 100 and 30 fold, respectively. On days 1 to 3 there was no detectable correlation between lipid peroxidation and fractional inspiratory oxygen. However, on days 4 and 5, lipid peroxidation and fractional inspiratory oxygen showed a significant correlation. Maximal amounts of expired ethane and pentane were significantly higher for patients with a poor outcome (five deaths, six cases of bronchopulmonary dysplasia) than for those with good outcome (eight infants surviving intact) (p less than 0.01). The results imply a role for free oxygen radicals in the pathogenesis of life-threatening complications in the very low birth weight infant.

Carbon Dioxide↗

Changes in surfactant in bronchoalveolar lavage fluid after hemithorax irradiation in patients with mesothelioma.

Experimental studies have shown that the surfactant system of the lung is affected shortly after irradiation. It is unclear, however, whether surfactant plays a role in the pathogenesis of radiation pneumonitis. In the present study surfactant components (saturated phosphatidylcholine, surfactant protein A, phosphatidylglycerol, and phosphatidylinositol) and other phospholipids of bronchoalveolar lavage fluid (BAL) were studied in four patients with pleural mesothelioma before and during hemithorax irradiation (70 Gy) as well as zero, 1, 2, 3, and 4 months following irradiation. The concentrations of these same components and of soluble proteins were also estimated in the epithelial lining fluid (ELF) using urea as a marker of dilution. After radiotherapy, the concentrations of the surfactant components in ELF decreased to 12 to 55% of the control values before radiation, whereas the concentration of sphingomyelin in ELF increased ninefold. There were small changes in the other phospholipids. The concentration of soluble protein in ELF increased sevenfold. The minimum surface activity of crude BAL increased from 12 +/- 4 to 32 +/- 6 mN/m, and that of the sediment fraction of BAL increased from 7 +/- 4 to 22 +/- 6 mN/m, p less than 0.001. The protein-rich supernatant fraction of BAL from irradiated lung had a inhibitory effect on normal surfactant. There were significant correlations between the increasing severity of the radiologic changes on the one hand and, on the other, the saturated phosphatidylcholine/sphingomyelin ratio (p less than 0.001), the concentrations of soluble protein (p less than 0.001), and the concentrations of the surfactant components (p less than 0.02-0.001) in ELF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Determination of ethane and pentane in free oxygen radical-induced lipid peroxidation.

It has been proposed that ethane and pentane reflect free oxygen radical-induced lipid peroxidation. However, methodological difficulties limit the use of these gases for assessment of free oxygen radical activity. In the present report we describe an improved method for the accurate analysis of picomole quantities (greater than or equal to 1 pmol) of ethane and pentane. They are first quantitatively trapped into an adsorbent and then heat-desorbed directly into a capillary column for gas chromatographic quantitation. During oxidation of linolenic (n-3) and linoleic (n-6) acid, ethane and pentane were formed, respectively. Nonstimulated granulocytes formed pentane. Upon addition of phorbol 13-myristate 12-acetate, the generation of pentane was increased by 540%. Addition of superoxide dismutase plus catalase inhibited lipid peroxidation in both a cell-free system and in isolated cells. The present method is useful in the evaluation of free oxygen radical induced damage.

Cell-Free System↗

Ceramide lactoside in amniotic fluid: high concentration in chorioamnionitis and in preterm labor.

The mechanisms responsible for the onset and progression of preterm labor are poorly understood. In the present study a total of 115 amniotic fluid specimens were analyzed for a lipid that has not previously been detected in amniotic fluid. This glycolipid was identified as ceramide lactoside. It was found in two-dimensional thin-layer chromatograms for evaluation of lung maturity and quantified by gas chromatography. Ceramide lactoside concentrations in amniotic fluid were low in spontaneous labor at term (1.7 +/- 0.7 nmol/ml) and in pregnancies that were not associated with spontaneous preterm labor (1.4 +/- 0.6 nmol/ml). The concentrations were high in chorioamnionitis with signs of infection (11.8 +/- 5.8 nmol/ml) and in preterm labor without clinical signs of chorioamnionitis (5.4 +/- 4.0 nmol/ml). A high ceramide lactoside (greater than or equal to 5 nmol/ml) predicted chorioamnionitis with signs of infection at a sensitivity and a specificity of 94% and 95%, respectively. A moderately high ceramide lactoside concentration (greater than or equal to 2.5 nmol/ml) predicted spontaneous preterm labor: sensitivity, 82%; specificity, 95%. Little, if any, ceramide lactoside was present in urine, vernix, normal fetal membranes, or lung effluent, whereas this glycolipid was present in large amounts in granulocytes and in inflamed fetal membranes. We propose that phagocytosing granulocytes release ceramide lactoside into amniotic fluid.

Amniocentesis↗

Surfactant proteins in the diagnosis of fetal lung maturity. II. The 35 kd protein and phospholipids in complicated pregnancy.

The major surfactant protein with a molecular weight of 35 kd and also saturated phosphatidylcholine and phosphatidylglycerol were analyzed in specimens of amniotic fluid; 68 were from cases of maternal diabetes, 41 from preeclampsia or maternal hypertension, 26 from premature rupture of the fetal membranes, and 45 from normal pregnancies. The relationship between the individual surfactant components was studied after covariance adjustment for the length of gestation. In severe early-onset preeclampsia, the 35 kd surfactant protein/saturated phosphatidylcholine ratio was significantly higher than in the other pregnancies. In diabetic pregnancies (classes B to D without preeclampsia), the phosphatidylglycerol/saturated phosphatidylcholine ratio was lower than in the other pregnancies. Isolated surfactant complex showed similar abnormalities. In severe early-onset preeclampsia and insulin-dependent diabetes without vascular disease, the phosphatidylglycerol/saturated phosphatidylcholine ratio correlated negatively with fetal growth. In four samples of amniotic fluids from cases of severe early-onset preeclampsia, the 35 kd protein falsely predicted lung maturity. All had abnormally high 35 kd protein/saturated phosphatidylcholine ratios (greater than 2 SD of controls). According to the present results, the 35 kd protein may give a false mature test result in severe preeclampsia.

Amniotic Fluid↗