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Biomedical subjects

M Hallman

Publications and source records attributed to M Hallman.

At least 127 records · Page 7Linked to original sources
PubMed1989

The severity of RDS during the first two neonatal days in relationship to fluid intake.

There are no generally accepted guidelines regarding the degree of hydration of small preterm infants with RDS. In the present prospective study, liquid intake (intravenous fluids, drugs, and enteral nutrition) during the first 48 h was correlated with the degree of respiratory failure at the age of two days in 120 consecutive, mechanically ventilated, small preterm infants with RDS (GA less than 30 w, BW less than 1,750 g). There was a positive linear relationship between the amount of liquids given and the degree of respiratory failure. Multiple regression analysis taking into consideration various perinatal factors revealed that the liquid intake explained the degree of respiratory failure (p less than 0.0001). The regression analysis revealed a similar dependence of respiratory failure on the liquid intake in the following groups of infants: GA less than 27 w (p = 0.023); GA 27-30 w (p = 0.005); SGA (p = 0.104); Non-SGA (p = 0.001); severe preeclampsia (p = 0.018); surfactant substitution (p = 0.002); liquid intake 127-240 ml/48 h (p less than 0.006); liquid intake 240-430 ml/48 h (p less than 0.047). The present results demonstrate the need to re-evaluate the optimal needs of hydration among infants with RDS during the very early neonatal period.

Causality↗
PubMed1989

Exogenous surfactant treatments for neonatal respiratory distress syndrome and their potential role in the adult respiratory distress syndrome.

Exogenous surfactant therapy has been recognised as an approach to alleviating the surfactant-deficine state for 3 decades. Natural and lipid-extracted surfactants derived from amniotic fluid, lung lavage, or lung homogenates are being used in worldwide clinical trials in premature infants. These studies are demonstrating a generally favourable influence on lung function by improving oxygenation and reducing the risk for pneumothorax and pulmonary interstitial emphysema. In some studies, reduction in death and the occurrence of bronchopulmonary dysplasia have been found. Numerous questions are unresolved and pharmacokinetic data are limited in preterm infants. Artificial surfactants are similarly under evaluation but current data demonstrate less overall effect. Adult respiratory distress syndrome has also been treated with exogenous surfactants. Although complex in terms of multiple initiating factors and in terms of high permeability of surfactant inhibitors, further studies are under way to determine the ideal methods of administration to enhance distribution and to monitor surfactant function in vivo.

Humans↗
PubMed1989

Prevention of neonatal group B streptococcal disease: intrapartum detection and chemoprophylaxis of heavily colonized parturients.

Parturients with heavy vaginal colonization of group B streptococci were selected randomly to receive either penicillin or no antibiotic. A simple and fast latex agglutination test, applied in 8977 consecutive parturients, detected 412 women with heavy colonization with group B streptococcus, 199 of whom were eligible for the study. The offspring of penicillin-treated women had a lower incidence of early-onset group B streptococcal disease (1.1%; 95% confidence interval 0-3.4%) than the controls (9.0%; 95% confidence interval 3.6--14.4%) (P less than .01). Among the offspring of streptolatex-negative parturients, the incidence of streptococcal disease was very low (0.07%). Thus, antibiotic prophylaxis of latex agglutination test-positive parturients would reduce the total incidence of group B streptococcal disease in the newborn by 25-80%.

Female↗
PubMed1989

Prostaglandins, inflammation, and preterm labor.

According to the current view, the fetal membranes and the amniotic fluid are central in transmission of signals resulting in labor and delivery. It has also become increasingly evident that although preterm and term labor share common pathways in activation of uterine contractions, the regulatory aspects are fundamentally different. The present article is a brief overview focusing on the participation of prostaglandins in human term and preterm labor. The involvement of bacteria in preterm labor is presented. In addition, it is proposed that inflammatory polymorphonuclear leukocytes promote preterm labor by activating prostaglandin production from human fetal membranes.

Arachidonic Acid↗
PubMed1989

Composition and function of pulmonary surfactant in adult respiratory distress syndrome.

There is a severe defect in the surfactant system in adult respiratory distress syndrome (ARDS). According to animal studies oxidant injury acutely alters the synthesis and secretion of surfactant. Plasma-derived surfactant inhibitors cause an early decrease in surface activity in high permeability lung oedema. Alveolar inflammation severely disturbs the surfactant system as a result of enzymatic breakdown of its components and inhibition of surfactant function. Analysis of bronchoalveolar lavage fluid obtained following unilateral irradiation of the lung revealed a striking increase in inhibitory serum proteins and a decrease in surfactant components (SP 35 apoprotein, phosphatidylglycerol, saturated phosphatidylcholine), before appearance of irradiation pneumonitis. In lysinuric protein intolerance (LPI), an autosomal recessive disorder in renal-intestinal-hepatic diamino acid transport, there is an increased risk of ARDS. In asymptomatic LPI the concentration of diamino acids in alveolar epithelial lining was strikingly increased, suggesting that the basolateral epithelial transport defect additionally involves alveolar epithelium and predisposes to ARDS.

Amino Acids↗
PubMed1989

Human surfactant in the treatment of respiratory distress syndrome. A spectrum of clinical responses.

Surfactant substitution is an incompletely studied, promising approach to treat respiratory distress syndrome (RDS). In this report we describe a spectrum of clinical responses following administration of human surfactant from amniotic fluid to 64 newborn infants. There was apparently no harm when surfactant was given to three infants with "mature" surfactant profile. Altogether 40% of the 42 "immature" small preterm infants (gestational age 26-29 weeks) required only a single dose, and 50% of them required two or three doses for successful treatment. In infants with persistent foetal circulation (6 cases) or hydrops (2 cases), there was only a transient or a small improvement of respiratory function. Most notably, the very small preterm infants (24-26 weeks, 15 cases) may require substantial increase in blood volume to prevent cardiac failure during the first neonatal day. We propose that the clinical response to exogenous surfactant can be improved by modifying the current management of very small preterm infants.

Amniotic Fluid↗
PubMed1989

Antigenicity of low molecular weight surfactant species.

The authors tested the antigenicity of human lung surfactant isolated from amniotic fluid. Mice and rabbits were immunized. Rabbit polyclonal antisera to these surfactant preparations were absorbed with normal human plasma proteins. Polyclonal antisera reacted with both high molecular weight (35 kd) surfactant apoprotein and to lower molecular weight species, both 18 kd and 9 kd. Mice were used to generate monoclonal antibodies to surfactant. Enzyme-linked immunosorbant assay was used to identify five monoclonal antibodies that reacted with surfactant. By Western blot analysis, all of these recognized a low molecular weight surfactant species (9 kd) that could be either SP-B or SP-C. One reacted with a 37 kd protein in the surfactant preparation, consistent with SP-A. One monoclonal antibody also recognized a higher molecular weight species (44 kd) of unknown origin. The ability of antisera and monoclonal antibodies to inhibit the functional activity of surfactant was assayed using a pulsating bubble surfactometer. Rabbit polyclonal antisera inhibited initial surface adsorption to equilibrium surface tension and increased the minimum surface tension after 1 and 5 minutes of initiation of pulsations. This inhibitory activity of the antisera was noted in divalent F(ab')2 fragments. Monovalent F(ab) fragments and control normal rabbit sera did not inhibit surfactant function in this assay. Of the anti-surfactant monoclonal antibodies that reacted with surfactant by ELISA and Western blot, three inhibited its capacity to lower surface tension on the pulsating bubble apparatus. The other two monoclonal antibodies showed no functional inhibitory activity. It is concluded that both the 35 kd SP-A and the 9 kd proteins of human surfactant are highly immunogenic and partially crossreactive. Resulting antibodies could alter the ability of surfactant to perform its physiologic function, ie, to lower surface tension.

Animals↗
PubMed1989

Surfactant replacement: immunological considerations.

We sought to analyse the potential immunogenicity of human alveolar surfactant as it is currently used in the treatment of neonatal respiratory distress syndrome (RDS). An enzyme linked immunosorbant assay capable of detecting specific immune complexes between surfactant and antibodies directed to surfactant was developed. Premature infants with RDS were divided into groups: one group received surfactant replacement and one received conventional therapy. Plasma samples obtained from these infants at birth and thereafter were examined for specific circulating immune complexes between surfactant and anti-surfactant antibodies. All babies were also examined for clinical and serological evidence of immune complex-mediated tissue damage. We found that almost all infants with RDS, regardless of their therapy, showed evidence of circulating surfactant-anti-surfactant immune complexes. Plasma samples from infants without RDS showed no such complexes. Immune complexes appeared early in postnatal life, usually within the first week, and diminished thereafter. We detected no evidence of altered plasma complement levels or end organ damage attributable to these immune complexes. Thus, circulating immune complexes between surfactant and antibodies to surfactant are common in neonatal respiratory distress syndrome, though they do not appear to cause injury. Since not only human but heterologous surfactants are now used in treating RDS, we feel that cautious evaluation of potential immune reactions to the administered materials should be undertaken.

Antigen-Antibody Complex↗
PubMed1988

Purification of a hydrophobic surfactant peptide using high-performance liquid chromatography.

A 4- to 6-kDa hydrophobic peptide (SP4-6) was purified from human pulmonary surfactant. Sep Pak Florisil cartridges removed most of the lipids and the 18-kDa peptide. Analytical wide-pore reversed-phase HPLC column separated a single peptide that contained no detectable lipids (less than 1 nmol/2.5 micrograms protein). N-terminal analysis indicated that this peptide was pure, but the N-terminal amino acid was blocked. The peptide was capable of restoring the in vitro surface properties of synthetic phospholipids, which is characteristic of native lung surfactant.

Chromatography, High Pressure Liquid↗
PubMed1988

Neurodevelopmental and respiratory outcome in early childhood after human surfactant treatment.

We assessed postnatal growth, neurodevelopmental outcome, and occurrence of respiratory illnesses in 46 infants of very low birth weight who were enrolled in a randomized, controlled, bicenter clinical trial of human surfactant treatment for respiratory distress syndrome. No long-term adverse effects of human surfactant treatment were detected between control and human surfactant-treated infants with respect to growth, neurologic, or developmental outcome. Infants with chronic lung disease, regardless of treatment group, had poorer growth and were more likely to have neurodevelopmental abnormalities at 12 to 24 months of age.

Brain Diseases↗
PubMed1988

Surfactant proteins in the diagnosis of fetal lung maturity. I. Predictive accuracy of the 35 kD protein, the lecithin/sphingomyelin ratio, and phosphatidylglycerol.

The concentration of the major surfactant protein with a molecular weight of 35 kD was determined in 469 amniotic fluid specimens from 284 pregnancies by the two-site simultaneous immunoassay with monoclonal antibodies. The predictive accuracy of the 35 kD protein was compared with that of the lecithin/sphingomyelin ratio and phosphatidylglycerol (the lung profile). Immature levels of 35 kD protein (less than 0.6 micrograms/ml) predicted 59% of all cases of respiratory distress syndrome (RDS) with an accuracy of 91%, and mature levels of 35 kD protein (greater than 3.0 micrograms/ml) predicted 68% of all infants who did not have RDS with an accuracy of 100%. The overall accuracy of the 35 kD protein in predicting the risk of developing respiratory distress syndrome was similar to that of the lung profile. In addition, testing with 35 kD protein improved the predictive value of an indeterminate lung profile (lecithin/sphingomyelin ratio of 1:1.9 and no phosphatidylglycerol) from 52% to 74%. The present results show that the lecithin/sphingomyelin ratio, phosphatidylglycerol, and 35 kD apoprotein have additive effects in improving the accuracy of the diagnosis of lung maturity.

Amniotic Fluid↗
PubMed1988

Respiratory failure caused by intratracheal saline: additive effect of xanthine oxidase.

Administration of physiological saline or drugs together with saline into the airways is becoming common clinical practice. However, there are few studies on possible side effects. We have studied the effects of saline, saline plus xanthine oxidase, and saline plus xanthine oxidase plus superoxidase dismutase on lung-thorax compliance and on arterial blood gases in anesthetized, paralyzed guinea pigs, ventilated for 2.5 h. Saline bolus (2-3 ml isotonic saline/kg body weight) into the airways reduced the compliance within 20 min to a mean of 39% of the pretreatment levels, and necessitated as increase in the respirator pressure. Saline plus xanthine oxidase decreased the compliance to 16% of the pretreatment levels. The xanthine oxidase-induced (but not saline-induced) decrease in lung compliance was relieved by superoxide dismutase. According to the present results xanthine oxidase induces a lung injury possible by production of free oxygen radicals. Superoxide dismutase can be valuable in prevention of free oxygen radical-mediated lung damage. Saline alone can be harmful when applied to the airways. This should be considered in clinical trials and in clinical practice.

Animals↗
PubMed1988

Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity.

Two low molecular weight (LMW) apoproteins were isolated from human pulmonary surfactant. SDS polyacrylamide gel analysis showed one protein (SP 18) to have an apparent molecular weight of 18,000 when unreduced and 9,000 D after reduction. The second protein (SP 9) migrated at approximately 9,000 D in the presence or absence of reducing agents. Both proteins contain a high number of hydrophobic amino acids. The NH2-terminal sequence of SP 18 was determined to be: NH2-phe-pro-ile-pro-leu-pro-tyr-. A cDNA clone isolated from a human adult lung cDNA library contained a long open reading frame encoding at an internal position the human SP 18 amino-terminal sequence. Mixtures of phospholipids (PL) and SP 9 and SP 18 were assessed for their capacity to reduce surface tensions on a pulsating bubble surfactometer. The addition of 1% apoprotein resulted in a reduction of surface tension after 15 s from 42.9 dyn/cm for PL alone to 16.7 and 6.3 dyn/cm for preparations containing SP 9 and SP 18, respectively. In vivo assessment of reconstituted surfactant activity was performed in fetal rabbits. Reconstituted surfactant consisting of PL + 0.5% SP 18 instilled intratracheally at delivery resulted in a marked increase in lung compliance, while the incorporation of 0.5% SP 9 yielded a moderate increase. These data show the ability to produce biologically active surfactant by the addition of isolated LMW apoproteins to defined PL.

Amino Acid Sequence↗
PubMed1988

Inositol and glucocorticoid in the development of lung stability in male and female rabbit fetuses.

Inasmuch as inositol affects the development of lung surfactant, and exogenous glucocorticoids accelerate fetal lung maturation, a possible interaction of the two substances on alveolar stability of preterm rabbit fetuses of 28 days gestation was investigated. On days 26 and 27 of gestation inositol or glucose were added to the diet of does treated with betamethasone (0.2 mg/kg intramuscularly on days 26 and 27). Inositol increased lung-thorax compliance of paralyzed fetuses at all insufflation pressures studied (from 16 to 22.5 and 30 cm H2O and back to 22.5, and 16 cm H2O). At a ventilation pressure of 30 cm H2O, lung-thorax compliance of fetuses treated with inositol plus betamethasone was more than doubled as compared with controls (1.2 +/- 0.6 versus 0.5 +/- 0.2 ml/kg x cm H2O; p less than 0.001). Inositol alone had no detectable effect on compliance, whereas betamethasone tended to increase compliance (p = 0.05). According to variance analysis, the effect of inositol was statistically significant only among the males. Inositol prevented the glucocorticoid-induced decrease in lung protein and, to a lesser extent, the decrease in DNA. Inositol did not further increase the lavageable surfactant pool of the glucocorticoid-treated, ventilated fetuses, although the area occupied by lamellar bodies within type II cells was increased after inositol plus betamethasone. According to the present study, inositol modifies the physiologic and biochemical response of the immature fetal lung to a pharmacologic dose of exogenous glucocorticoid.

Animals↗
PubMed1988

Immunologic consequences of exogenous surfactant administration.

In conclusion, we have shown that human surfactant is immunogenic and that circulating surfactant-antisurfactant immune complexes are detectable in the plasma from infants and in adults with RDS. We found these immune complexes regardless of whether exogenous surfactant was used in the individual treatment regimen. These immune complexes do not yet seem to cause disease in the short term. Long-term effects, if any, are unknown. Indications for surfactant replacement therapy in neonatal RDS are clear. Trials of exogenous surfactant are just beginning in adult RDS, and potential immunogenicity will be of even greater concern in these patients. In all such situations, potential for side effects must be balanced against therapeutic efficacy and the gravity of the disease. Our data indicate that surfactants, particularly heterologous surfactants, are potent immunogens. One cannot assume that using homologous or heterologous surfactants in patients with RDS will always be immunologically innocuous. Nonetheless, based on present data, moderately long-term follow-up (2 to 4 years), we are encouraged by our observation that no selective adverse effects attributable to human surfactant have been recognized, yet mortality from RDS in infants less than 30 weeks has been nearly cut in half.

Adult↗
PubMed1988

Immunomodulation by pulmonary surfactant.

Canine pulmonary surfactant is recognized to modulate both T and B cell response in vitro. Because both responses involve cell proliferation, it has been suggested that surfactant interferes with the proliferation of lymphocytes. We herein report studies using human surfactant collected from amniotic fluid (HAFS). HAFS inhibited the proliferative response of human lymphocytes to antigen (PPD) and to allogeneic lymphocytes. Inhibition was linear within the dose range examined. Inhibition of the response to phytohemagglutinin was only evident when suboptimal doses of phytohemagglutinin were used. The effect of HAFS on the lysis of K562 human myeloid target cells by natural killer (NK) cells was also studied. Lysis in this system does not require proliferation. HAFS inhibited NK cell-induced lysis by 70% (250 micrograms HAFS per milliliter) to 95% (500 micrograms HAFS per milliliter). Inhibition was evident whether the cells were incubated with HAFS for 4 hours or for 18 hours. The NK suppressor activity was contained in the lipid fraction of HAFS, whereas the protein fraction revealed little activity. The washout experiments demonstrated that the action of HAFS was on NK cells and not on target cells. The immunomodulatory properties of surfactant affect NK cell activity and the proliferative response. Surfactant may protect the lungs from inappropriate immune reactions. Abnormalities of the lipid fraction of surfactant should be considered in studies of the mechanism of pulmonary diseases characterized by local pulmonary immune responses.

Amniotic Fluid↗