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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
PubMed2002

Variation in mortality and intraventricular haemorrhage in occupants of Pacific Rim nurseries.

OBJECTIVE: A network of neonatal intensive care units in Pacific Rim countries was formed to compare infant risk factors, clinical practices, and outcomes for very low birthweight infants. METHODOLOGY: A multicentre, prospective study compared outcomes for infants born smaller than 1501 g or at less than 31 weeks gestation. RESULTS: Gestational age-specific survival and incidence of intracranial haemorrhage varied for infants born in these nurseries. We found differences in infant risk factors among the nurseries. There were also significant differences in the use of antenatal steroids, but similar rates for Caesarean section and surfactant treatment. The factor most predictive of neonatal death and severe intracranial abnormality was an elevated Clinical Risk Index for Babies (CRIB) score. Antenatal steroid treatment (>24 h prior to delivery) was associated with improved survival and decreased incidence of severe intracranial abnormalities. Antenatal steroid treatment for less than 24 h prior to delivery was not associated with improved survival. Caesarean delivery was associated with improved survival, but showed no benefit regarding the incidence of severe intracranial abnormality. CONCLUSIONS: Our Pacific Rim nursery network found differences in neonatal outcomes that correlated best with measures of neonatal risk at birth, antenatal steroid treatment, and Caesarean delivery. These data emphasize the importance of obstetric care to improve postnatal outcomes in premature infants, and highlight the usefulness of CRIB scores in these patients.

Analysis of Variance↗
PubMed2001

Polyethylene glycol/surfactant mixtures improve lung function after HCl and endotoxin lung injuries.

Addition of nonionic polymers such as polyethylene glycol (PEG) and dextran ameliorates inactivation of Survanta by a variety of substances in vitro. Addition of polymers to Survanta also improves pulmonary function when used to treat rats with lung injury caused by instillation of human meconium. To find whether this approach is effective in lung injuries that more closely resemble adult respiratory distress syndrome (ARDS), we have compared the use of Survanta with Survanta + PEG in two additional models of lung injury caused by either lipopolysaccharide (LPS) or HCl in adult rats. Significant improvement of serial measures for arterial oxygenation and of postmortem pressure-volume measurements were found after treatment with Survanta + PEG compared with Survanta alone. PEG added to Survanta increased resistance to inactivation caused by tracheal fluid taken from animals injured with HCl. Other work suggests that PEG promotes surfactant aggregation, separates surfactant from surfactant inhibitors, and enhances access of surfactant to the gas-liquid interface. The addition of polymers to surfactants may also be useful in the treatment of lung injury where inactivation of surfactant has already occurred.

Animals↗
PubMed2000

Treatment of acute (Adult) respiratory distress syndrome. The holy grail of surfactant therapy.

The treatment of neonatal respiratory distress syndrome with surfactant represents a successful culmination of decades of basic and clinical research. In many babies, respiratory distress syndrome is a relatively pure expression of surfactant deficiency. Acute respiratory distress syndrome (ARDS) is a more common disease that is most frequently seen in adults, but the processes are common to lung injuries in newborns and children as well. While some impairment of production and secretion of surfactant constituents may be present in ARDS, surfactant inactivation is probably a more important factor in this disease. Until recently, surfactants available for human use have been easily susceptible to inactivation and this may explain why they have been less successful for treatment of ARDS than for neonatal respiratory distress syndrome. This review outlines recent information on surfactant inactivation and describes initiatives that may result in 'inactivation-proof' surfactants that may be of increased benefit in ARDS.

Acute Disease↗
PubMed1999

Hyperphagia in neonates withdrawing from methadone.

AIMS: To examine whether hyperphagia is a clinically significant problem in infants born to women receiving methadone maintenance. METHODS: The volume of feeds, changes in infant body weight, as well as occurrence of adverse clinical effects in infants withdrawing from methadone were studied during the first month of life. A retrospective chart review was conducted for all infants at San Francisco General between 1992 and 1995, born to women receiving methadone maintenance during their pregnancy. Forty four infants were identified and the data obtained from hospital medical records. The daily oral intake of these infants was recorded during the first month of life. The incidence of hyperphagia (oral intake > 190 cc/kg/day) was measured. Associations between infant oral intake and maternal methadone dose were studied using correlation analysis as well as Anova for repeated measures. Adverse clinical symptoms were also recorded. A subset of premature infants was studied separately. RESULTS: The incidence of hyperphagia was 26% by day 8 and 56% by day 16 of life in the infants. Hyperphagia was not associated with maternal methadone dose or with infant withdrawal scores. Infants who were hyperphagic lost significantly more weight during the first week of life than those who were not. Despite significantly greater intake, the hyperphagic infants did not gain weight more rapidly during the first month of life compared with those infants with lower oral intake. Infants who were hyperphagic (maximum intake of 290 cc/kg/day) did not experience increased vomiting, aspiration, diarrhoea, or abdominal distention. CONCLUSIONS: Hyperphagia is commonly found in infants withdrawing from methadone and can be persistent in a significant number. Hyperphagia was not associated with either increased neonatal weight gain or with adverse gastrointestinal consequences. Hyperphagia may occur in infants withdrawing from methadone who have high metabolic demands due to clinical signs not controlled by opiate treatment.

Adult↗
PubMed1997

Effects of cationic liposome-DNA complexes on pulmonary surfactant function in vitro and in vivo.

Cationic liposome-DNA complexes are being evaluated as potential gene therapy agents for the lung. Cations have strong effects on the biophysical functions of lung surfactant. Therefore, we assessed whether cationic liposomes [composed of N-(1-(2,3-dioleyloxy) propyl)-N,N,N-trimethyl-ammonium chloride and dioleylphosphatidylethanolamine] with or without DNA affect behavior of four types of surfactant in vitro. Experiments were carried out using a modified Wilhelmy surface balance. The ability of surfactants that contain protein and anionic lipids to lower surface tension was inhibited in the presence of cationic liposomes. Inactivation was less when DNA was preincubated with cationic liposomes. Surfactant that contained neither protein nor anionic lipids was not inactivated. Mechanical properties of the lung were studied to assess in vivo surfactant function after intratracheal instillation of a cationic liposome-DNA complex into adult rats. Pressure-volume deflation curves were shifted by 18% compared with those from normal (untreated) animals, but this effect was transient and not different from that observed in animals who received a similar volume of saline. These findings indicate that cationic liposomes alone may have deleterious effects on behavior of some surfactants possibly by disrupting charge interactions between negatively charged phospholipids and surfactant proteins. When DNA is added to liposomes before exposure to surfactants, the adverse charge interactions may be obviated by charge neutralization of liposomes by DNA.

Animals↗
PubMed1996

Conformation and molecular topography of the N-terminal segment of surfactant protein B in structure-promoting environments.

Although the effects of surfactant protein B (SP-B) on lipid surface activity in vitro and in vivo are well known, the relationship between molecular structure and function is still not fully understood. To further characterize protein structure-activity correlations, we have used physical techniques to study conformation, orientation, and molecular topography of N-terminal SP-B peptides in lipids and structure-promoting environments. Fourier transform infrared (FTIR) and CD measurements of SP-B1-25 (residues 1-25) in methanol, SDS micelles, egg yolk lecithin (EYL) liposomes, and surfactant lipids indicate the peptide has a dominant helical content, with minor turn and disordered components. Polarized FTIR studies of SP-B1-25 indicate the long molecular axis lies at an oblique angle to the surface of lipid films. Truncated peptides were similarly examined to assign more accurately the discrete conformations within the SP-B1-25 sequence. Residues Cys-8-Gly-25 are largely alpha-helix in methanol, whereas the N-terminal segment Phe-1-Cys-8 had turn and helical propensities. Addition of SP-B1-25 spin-labeled at the N-terminal Phe (i.e., SP-B1-25) to SDS, EYL, or surfactant lipids yielded electron spin resonance spectra that reflect peptide bound to lipids, but retaining considerable mobility. The absence of characteristic radical broadening indicates that SP-B1-25 is minimally aggregated when it interacts with these lipids. Further, the high polarity of SP-B1-25 argues that the reporter on Phe-1 resides in the headgroup of the lipid dispersions. The blue-shift in the endogenous fluorescence of Trp-9 near the N-terminus of SP-B1-25 suggests that this residue also lies near the lipid headgroup. A summary model based on the above physical experiments is presented for SP-B1-25 interacting with lipids.

Amides↗
PubMed1996

Inactivation of surfactant in rat lungs.

Although surfactant replacement therapy has dramatically improved the outcome of premature infants with respiratory distress syndrome, approximately 30% of treated infants show a transient or no response. Nonresponse to surfactant replacement therapy may be due to extreme lung immaturity and possibly surfactant inactivation. Surfactant inactivation involves aspecific biophysical events, such as interference with the formation or activity of an alveolar monolayer, and specific interactions with serum proteins, including antibodies, leaking into the alveolar space. As formulations containing surfactant proteins appear to better tolerate serum inactivation, we used an excised rat lung model to compare the susceptibility to serum inactivation of a mixture of synthetic phospholipids selected from surfactant lipid constituents, Exosurf (a protein-free synthetic surfactant), Survanta [containing surfactant proteins B and C (SP-B and -C)], and a porcine surfactant (containing SP-A, -B, and -C). For each of these preparations, we used pressure/volume determinations as an in situ measure of surfactant activity and retested the same preparations after mixing with human serum, a nonspecific surfactant inactivator. Human serum inactivated porcine surfactant to a lesser extent than Survanta, Exosurf, or synthetic phospholipids. Temperature exerted a significant effect on deflation stability, as shown by a greater lung compliance in untreated, normal lungs and a larger improvement in compliance after treating lavaged lungs with synthetic phospholipids at 37 degrees C than at 22 degrees C. We conclude that surfactant containing SP-A, -B, and -C is only moderately susceptible to inactivation with whole serum and may therefore exert a greater clinical response than protein-free surfactants or those containing only SP-B and -C.

Animals↗
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↗