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Biomedical subjects

H W Taeusch

Publications and source records attributed to H W Taeusch.

At least 19 recordsLinked to original sources
PubMed1996

Surfactant replacement therapy for meconium aspiration syndrome.

OBJECTIVE: The pathophysiology of meconium aspiration syndrome (MAS) is related not only to mechanical obstruction of the airways and chemical injury to the respiratory epithelium but also to surfactant inactivation by meconium. A randomized, controlled study was performed to determine whether high-dose surfactant therapy improves the pulmonary morbidity of term infants ventilated for MAS. METHODS: Forty term infants receiving mechanical ventilation for MAS were enrolled in this trial, in which the infants in the study group (n = 20) received up to four doses of 150 mg (6 mL)/kg beractant (Survanta), instilled every 6 hours by continuous infusion for 20 minutes via a side hole endotracheal tube adapter, and the infants in the control group (n = 20) received 6 mL/kg air placebo. RESULTS: Mean arterial-to-alveolar PO2 ratio values increased from 0.09 to 0.11 at 1 and 6 hours with a concomitant slight decrease in oxygenation index values from 23.7 to 19.7 at 1 hour and 20.7 at 6 hours after the first dose of surfactant. Oxygenation improved cumulatively after the second and third dose of surfactant, with mean arterial-to-alveolar PO2 ratios and oxygenation indices of 0.18 and 12.1 at 6 hours after the second dose of surfactant and 0.31 and 5.9 at 6 hours after the third dose of surfactant, eliminating the need for a fourth dose in any infant in the study group. After three doses of surfactant, persistent pulmonary hypertension had resolved in all but one of the infants in the study group versus none of the infants in the control group. No air leaks developed in any of the 20 infants in the study group after surfactant therapy, and only 1 infant required extracorporeal membrane oxygenation. Air leaks developed in 5 of the 20 infants in the control group, and 6 underwent extracorporeal membrane oxygenation. The duration of mechanical ventilation, oxygen therapy, and admission was significantly shorter in the surfactant group than in the control group. CONCLUSION: Surfactant replacement therapy, if started within 6 hours after birth, improves oxygenation and reduces the incidence of air leaks, severity of pulmonary morbidity, and hospitalization time of term infants with MAS.

Biological Products↗
PubMed1995

Time of onset of necrotizing enterocolitis in newborn infants with known prenatal cocaine exposure.

Cocaine exposure can lead to diminished gut-blood supply and thereby contribute to the pathogenesis of necrotizing enterocolitis (NEC). Investigating the hypothesis that NEC occurs at a younger age in cocaine-exposed infants, we reviewed 1,284 neonatal intensive care admissions. Infants with NEC were divided into cocaine-exposed and cocaine-nonexposed groups, each subdivided into two birth-weight groups, using 1,500 g as the cutoff weight. Time of onset of NEC for each infant was determined and survival curves for the cocaine-exposed and nonexposed groups were calculated using their birth-weight subdivision. Hazard function curves were done. Neonatal risk factors in both groups were compared. Twelve percent (28/231) of cocaine-exposed infants developed NEC stage II or III versus 3% (34/1053) in the nonexposed group (P < 0.05). Eight percent of cocaine-exposed and 2% of nonexposed survivors had NEC by day 7 versus 20% and 5% by day 28 after birth (P < 0.05). Infants > 1,500 g were at risk for NEC until day 8 only, whereas infants < or = 1,500 g had both an early and continuing risk for NEC with a biphasic pattern of onset. The accentuated peak in early-onset NEC may be attributed to antenatal cocaine exposure, while late-onset NEC in the < or = 1,500 g group probably relates to a variety of pathogenetic factors.

Age of Onset↗
PubMed1995

Lysis of red blood cells and alveolar epithelial toxicity by therapeutic pulmonary surfactants.

The risk of pulmonary hemorrhage is increased in extremely low birth weight infants treated with surfactant. The pathogenesis of this increased risk is far from clear. We tested whether exposure of cell membranes to surfactant may lead to increased membrane permeability, hypothesizing that this process may contribute to the occurrence of alveolar hemorrhage after surfactant treatment. Aliquots of washed packed red blood cells (used as membrane model) were suspended in 0.9% NaCl with various concentrations of Survanta or Exosurf for either 2 or 24 h at 37 degrees C. Cytolysis was measured by spectrophotometric determination of free Hb after centrifugation. Red cells suspended in 0.9% NaCl alone, distilled water, or various concentrations of melittin were used as negative and positive controls. Both surfactants were associated with increased hemolysis to 35% of maximum at concentrations of 1.25 mg/2 mL. Above these concentrations, Survanta was associated with no increase in hemolysis, whereas Exosurf increased hemolysis to 60% of maximum at concentrations of 12.5 mg/2 mL. In additional experiments, primary cultures of alveolar type II cells from adult rats were treated with Survanta, Exosurf, the Exosurf components tyloxapol and hexadecanol, melittin, or culture medium alone. After 24 h of incubation, lactate dehydrogenase release into the media was measured as a percent of total lactate dehydrogenase activity to indicate cytotoxicity. Lactate dehydrogenase release was < 10% for control experiments but increased sharply with Exosurf and its components tyloxapol and hexadecanol. These results indicate that surfactant may be associated with in vitro cytotoxicity and that this property differs for different surfactants and different dosages.

Animals↗
PubMed1995

Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles.

To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner-city hospitals.

Adult↗
PubMed1994

Comparison of captive and pulsating bubble surfactometers with use of lung surfactants.

We compared surface tension measures of surfactants with various surface activities by using a pulsating bubble surfactometer (PBS) and a captive bubble surfactometer (CBS). Rabbit lung lavage surfactant (60,000 x average g for 60 min), bovine surfactant extract (Survanta), and a synthetic lipid surfactant mixture (dipalmitoylphosphatidylcholine-egg phosphatidylglycerol-palmitic acid) were studied at 1.25 mg phospholipid/ml. The PBS was used either unmodified according to manufacturer's instructions or with the sample chamber capillary kept dry and the sample adsorbing at maximum bubble size (5 min). The CBS was used in a manner that imitated the unmodified PBS. We found that all three techniques indicated low surface tension on the first cycle for 60K. For Survanta, the CBS and the modified PBS reported low surface tension on the first cycle, whereas the unmodified PBS did not achieve this within 10 cycles. For the synthetic lipid surfactant mixture, only the CBS measured low surface tension within 10 cycles. Video observations indicate that the modified PBS performs better than the unmodified PBS because keeping the capillary dry prevents surface film from occupying this large surface during cycling, thereby allowing larger area compressions.

Adsorption↗
PubMed1994

Gestational age, birthweight, and neonatal mortality for extremely premature inner-city African-American and Latino infants.

This article analyzes birthweight, gestational age, and inhospital survival for 233 extremely premature infants born at an inner-city hospital over the past 5 years. Results for gestation-specific birthweights and survival did not differ between inner-city Hispanic and African-American infants born at 24 to 28 weeks of gestation. For infants with gestation of 23 to 28 weeks, weight at birth increased by approximately 100 g/week gestation. Survival rates increased from 15% at 23 weeks to 75% by 28 weeks gestation. Survival in this sample was strongly affected by respiratory distress syndrome, air leak, and birthweight. Prenatal steroids administered to the mother had a significant effect on improving survival using univariate analysis and was at the limits of statistical significance using logistic regression. Other maternal, obstetric, and neonatal factors had little or no effects on survival in this group of very immature infants.

Black or African American↗
PubMed1994

Modified bovine surfactant (Survanta) versus a protein-free surfactant (Exosurf) in the treatment of respiratory distress syndrome in preterm infants: a pilot study.

We undertook a prospective, randomized, non-blinded pilot study to determine whether infants with respiratory distress syndrome (RDS) who were treated with protein-containing bovine surfactant (Survanta, Ross/Abbott Laboratories, Columbus, Ohio) had earlier and larger responses in gas exchange when compared with similar infants treated with a synthetic surfactant (Exosurf, Burroughs Wellcome, Research Triangle Park, North Carolina). Forty-one infants weighing between 600 g and 1750 g at birth with RDS of sufficient severity to require assisted ventilation with an FiO2 > 0.39 were enrolled in the study and treated with surfactant from 1 to 8 hours after birth. Infants were randomly selected to receive treatment with either Exosurf or Survanta. Despite randomization, the Survanta group was overrepresented with factors associated with greater severity of RDS (lower birthweight, more males, and fewer African Americans). No statistically significant difference was found in the primary outcome measure (arterial/alveolar PaO2 > 0.3 at 24 hours) by univariate or multivariate analysis. The percentage of responders in the Survanta-treated group was significantly increased 24 hours after treatment in two of four secondary measures of oxygenation when analyzed by univariate tests using one-tailed P values. Based on these results, we anticipate that acute outcomes after Survanta or Exosurf will approximate those found in this trial and that differences in measures of oxygenation between treatment groups will approximate 30% to 50% 24 hours after initial treatment.

Biological Products↗
PubMed1993

Full length synthetic surfactant proteins, SP-B and SP-C, reduce surfactant inactivation by serum.

The failure of some infants with respiratory distress syndrome to respond to therapy with surfactant may be explained in part by inactivation of surfactant caused by leakage of plasma constituents into air spaces. Surfactant-associated proteins (SP-A, SP-B and SP-C) reduce the susceptibility of surfactants to inactivation in vitro. To study this phenomenon further, we used full length synthetic proteins, SP-B [1-78] and SP-C [1-31], mixed with surfactant lipids in different ratios and different concentrations. Equilibrium and minimum surface tensions of these mixtures, with or without serum and calcium, were measured using a pulsating surfactometer. Mixtures containing both SP-B and SP-C had optimal minimum and equilibrium surface tensions of < 5 and < 28 mN/m, respectively. Mixtures with SP-B had optimal minimum surface tensions, but equilibrium surface tensions averaged 35 mN/m. Mixtures with SP-C had high minimal (19 mN/m) and high equilibrium surface tensions (35 mN/m). When serum was added to these mixtures, the least inactivation was found with mixtures containing 3% protein at 1:1 ratio of SP-B/SP-C with 2 mM calcium chloride. These data indicate that SP-B and SP-C, particularly in the presence of calcium, reduce surfactant inactivation that may be caused by plasma constituents. The results lead to the hypothesis that charge interactions among ions, lipids, surfactant proteins, and serum inactivators are a major element in pathophysiological surfactant inactivation.

Adult↗
PubMed1993

Reversible and irreversible inactivation of preformed pulmonary surfactant surface films by changes in subphase constituents.

Several mechanisms for surfactant inactivation have been reported. In this study, we have measured the reversibility of surfactant inactivation caused by various lipid or protein constituents of plasma or by pH changes. A surfactant of bovine origin was studied in a pulsating surfactometer either when surfactants were premixed with different serum constituents (inactivators) or when inactivators were introduced into subphase fluid surrounding surfactant films formed at an air-liquid interface. Subphase exchanges with sodium bicarbonate or sodium borate raised pH and raised minimal surface tensions either when premixed with surfactant or when introduced with saline subphase beneath a preformed surfactant surface film. The pH effects on surfactant film function were reversible for sodium bicarbonate but not for sodium borate when the subphase with bicarbonate or borate was replaced with saline. Lipids (platelet-activating factor or lysophosphatidylcholine) had non-reversible effects on preformed films. Proteins (fibrinogen or C reactive protein) had reversible effects at low concentrations, but reversibility was less evident at high concentrations. Effects with whole serum were non-reversible at low protein concentrations (0.5 mg/ml). These results add evidence that surfactant inactivation can be caused by multiple mechanisms, both reversible and irreversible.

Animals↗
PubMed1993

Morbidity of low-birthweight infants with intrauterine cocaine exposure.

The effects of intrauterine cocaine exposure on 158 low-birthweight infants (500 g to 2500 g) were compared with 536 low-birthweight infants not known to be exposed to cocaine who were admitted to our neonatal intensive care unit. Univariate analyses indicated that drug-exposed infants had lower birthweights when compared with control infants. Frequency of necrotizing enterocolitis differed between the drug-exposed infants and controls (11% versus 6%). Frequency of severe respiratory distress syndrome, severe intraventricular hemorrhage, and bronchopulmonary dysplasia did not differ between groups of similar birthweight. We conclude that the most evident risks of prenatal cocaine exposure are low birthweight and increased incidence of necrotizing enterocolitis.

Cocaine↗
PubMed1991

Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

The mechanisms by which pulmonary surfactant protein B (SP-B) affects the surface activity of surfactant lipids are unclear. We have studied the peptide/lipid interactions of the amino-terminal amphipathic domain of SP-B by comparing the secondary conformations and surface activities of a family of synthetic peptides based on the native human SP-B sequence, modified by site-specific amino acid substitutions. Circular dichroism measurements show an alpha-helical structure correlating with the ability of the peptides to interact with lipids and with the surface activity of peptide/lipid dispersions. Amino acid substitutions altering either the charge or the hydrophobicity of the residues lowered the helical content and reduced the association of the aminoterminal segment with lipid dispersions. Surface activity of peptide/lipid mixtures was maximally altered by reversal of charge in synthetic peptides. These observations indicate that electrostatic interactions and hydrophobicity are important factors in determining optimal structure and function of surfactant peptides in lipid dispersions.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

Inhibition of mixtures of surfactant lipids and synthetic sequences of surfactant proteins SP-B and SP-C.

The respiratory distress syndrome of premature infants is caused by both surfactant deficiency and surfactant inhibition by capillary-alveolar leakage of serum factors. Dispersions of a standard surfactant lipid mixture, with and without various synthetic peptides, modeled on human surfactant proteins SP-B (residues 1-25, 49-66, 1-78) and SP-C (residues 1-10), were evaluated for inhibition by serum and by plasma constituents using a pulsating bubble surfactometer. Inhibition was derived from the changes in surface properties of these mixtures after addition of human serum or plasma constituents. Modified bovine surfactant (TA) containing native SP-B and SP-C was used as a control. In the absence of serum inhibitors, mixtures with synthetic peptides gave results similar to surfactant TA. However, inhibition was more evident in the dispersions with synthetic peptides when compared with surfactant TA. The peptide/phospholipid mixture with the entire sequence of SP-B and the first 10 residues of SP-C were more resistant to inhibition than mixtures with synthetic peptides containing fewer domains. Addition of calcium reduced the inhibitory effects of serum both in mixtures containing synthetic peptides and in surfactant TA. Therefore, synthetic SP-B and SP-C peptides in surfactant lipids, in cooperation with calcium, permit resistance to inhibition by several plasma constituents that probably inactivate surfactant by a variety of different mechanisms.

Adult↗
PubMed1991

Antibodies against synthetic amphipathic helical sequences of surfactant protein SP-B detect a conformational change in the native protein.

Synthetic peptides based on the native human sequence of surfactant protein B have been used to generate polyclonal monospecific antibodies against specific segments of the native SP-B protein. Circular dichroism analysis of the synthetic peptides shows they have a dominant helical content in structure promoting environments and tensiometric measurements indicate these peptides lower surface tension at air-water interfaces implying that they contain amphipathic alpha helical motifs. Antibodies directed against the C-terminal segment of SP-B react with the native protein in the oxidized and reduced state. Antibodies directed against the N-terminal sequence of SP-B react with the native protein only in the reduced state suggesting that this domain has a conformation dependent on disulfide bond formation.

Amino Acid Sequence↗
PubMed1991

Radiographic findings associated with surfactant treatment.

Radiographs of the chest (CXR) were evaluated in 35 of 41 infants enrolled in a randomized controlled trial of modified bovine surfactant extract (Surfactant-TA Tokyo-Tanabe) treatment. Infants between birthweight 1000 and 1500 gm with respiratory distress syndrome requiring mechanical ventilation and an inspired oxygen concentration 0.4 or greater were randomly assigned to either a single intratracheal dose of saline or surfactant-TA prior to 8 hours of age. Radiographs obtained prior to treatment and 24 hours after treatment were reviewed by a radiologist (N.T.G.) without knowledge of treatment group. Evaluation consisted of a score including criteria for inflation of the lungs, density of the lungs, and extent of air bronchograms. Pneumothorax, pulmonary interstitial emphysema, and asymmetric parenchymal involvement were noted as well. No significant difference in CXR scores were noted in the two groups, before or after treatment. There was a greater incidence of pneumothorax and pulmonary interstitial emphysema in the control infants, which supports the role of surfactant in preventing barotrauma. Increased incidence of asymmetric parenchymal involvement was noted in the surfactant-treated infants. Further study of the possibility of drug maldistribution is warranted.

Female↗
PubMed1991

Surfactant proteins and anti-surfactant antibodies in sera from infants with respiratory distress syndrome with and without surfactant treatment.

The presence of surfactant protein antigenemia and of surfactant protein antibodies was determined in serum from surfactant-treated and control infants with respiratory distress syndrome who were enrolled in a prospective randomized clinical trial. The surfactant used for treatment (surfactant TA) contained surfactant proteins (SPs) B and C and no SP-A. Enzyme-linked immunosorbent assays (ELISAs) that identify surfactant-associated proteins and ELISAs that identify IgG or IgM directed against surfactant proteins were used to investigate sera from these infants obtained prior to treatment, at 1 week of age, and at 2 months of age. There were no significant differences between average values in the surfactant-treated and control groups at each time period. However, in the control group, averaged results from ELISAs that identify SP-A and that identify IgM antibodies to SP-A or to SP-B, C showed significant differences between pretreatment sera and sera obtained at 1 week of age. No significant differences were noted in averaged results for IgG. Positive ELISA values were more frequently found in the control group than in the surfactant-treated group with regard to SP-A, and IgM against SP-A and SP-B, C in sera from neonates at 1 week of age. No positive ELISA values were found in sera from infants at 2 months of age. It is concluded that some patients with severe respiratory distress syndrome presumably leak surfactant proteins into the circulation and that this induces transient low titers of IgM antibody. This occurrence is decreased with surfactant treatment. Surfactant treatment may reduce leak of surfactant proteins into the vascular space by reducing lung damage.

Animals↗
PubMed1990

Structure-function relationships of bovine pulmonary surfactant proteins: SP-B and SP-C.

Pulmonary surfactant contains at least three unique proteins: SP-A, SP-B and SP-C. SP-B and SP-C from bovine surfactant are markedly hydrophobic and have molecular masses between 3 and 26 kDa. We identify surfactant proteins under nonreducing conditions on polyacrylamide gels with approximate molecular mass of 5, 14, 26 kDa (SP-5, 14, 26) when organic solvent-soluble material is eluted from a Sephadex LH-20 size exclusion column followed by separation on a high-performance reverse-phase chromatography system. These bands correspond to monomeric SP-C, oligomeric SP-C and oligomeric SP-B, respectively. Computer analysis (Eisenberg-hydrophobic moment) of sequences for these proteins suggests that SP-B contains surface-seeking amphiphilic segments. In contrast, SP-C resembles a more hydrophobic transmembrane anchoring peptide. Dispersions containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, palmitic acid and multimeric SP-B and SP-C duplicate the surface activity of natural surfactant when assayed in a pulsating bubble surfactometer. We speculate that oligomers of SP-B and monomers and oligomers of SP-C may act cooperatively in affecting surfactant function. An important function of SP-B and SP-C may be to affect the ordering of surfactant lipids so that rates of transport of surfactant lipids to the hypophase surface in the alveoli are enhanced.

Amino Acid Sequence↗
PubMed1990

Health and developmental outcomes of a surfactant controlled trial: follow-up at 2 years.

Several randomized clinical trials have shown that surfactant therapy improves the pulmonary status of infants with respiratory distress syndrome and has the potential to reduce morbidity and mortality in these infants. Relatively little is known, however, about the long-term consequences of surfactant treatment. In this report, the results of health and developmental assessment are described at 1 and 2 years of age of 32 survivors of an initial group of 41 infants enrolled in a randomized clinical trial of bovine surfactant therapy. The frequencies of abnormal findings were comparable in the two groups although there was a trend toward a greater frequency of allergic manifestations in the control group (6 of 16 (38%) vs 1 of 15 (7%), P = .08). Similarly, no differences were seen in the mental and motor scores of the Bayley Scales of Infant Development at either 1 or 2 years of age. This study and other recently published reports of follow-up studies of infants treated with surfactant provide encouraging evidence that major long-term side effects do not result from surfactant therapy.

Animals↗