Oxidation of proteins in neonatal lungs.

OBJECTIVE: To develop a method capable of quantifying the oxidative modification of proteins in pulmonary fluid obtained during routine suctioning of neonates receiving ventilation, thus providing an integrated assessment of antioxidant defenses. DESIGN: Consecutive sample of neonates receiving ventilation. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-six neonates receiving ventilation with a gestational age of 24 to 42 weeks, from whom 246 samples were collected and analyzed. MEASUREMENTS AND RESULTS: The carbonyl content in the lavage samples was measured by reaction with 2,4-dinitrophenylhydrazine followed by high-pressure liquid chromatography. Oxidation of proteins caused introduction of carbonyl groups into the side chains of the protein, providing a convenient and relatively specific marker of oxidative damage. On the first day of life, the initial protein-bound carbonyl for each neonate was usually low and consequently was not significantly related to birth weight, gestational age, or initial ventilatory requirements. Examination of the changes in pulmonary protein carbonyl in the first days of life revealed correlations of interest. In the first day of life, four neonates whose average inspired oxygen were < 40% showed no increase in carbonyl content, whereas four neonates whose inspired oxygen was > 40% showed an average increase in carbonyl of 51% (P < .001). Also, the need for ventilation > 3 days was correlated with elevated carbonyl in those first 3 days. The carbonyl content averaged over the first 3 days was 0.13 +/- 0.02 mol carbonyl/mol protein for the eight neonates receiving ventilation < 72 hours, whereas the nine needing longer ventilation had a carbonyl content of 0.28 +/- 0.03 mol carbonyl/mol protein (P < .05). Seven neonates were treated with dexamethasone because of ventilator dependence at 14 days of age. In these neonates, treatment was associated with a 50% reduction in carbonyl content within 48 hours (P < .02). CONCLUSIONS: Oxidative damage to pulmonary proteins can be quantitated in samples obtained during routine suctioning of neonates receiving ventilation. The amount of oxidatively modified protein may provide a quantitative assessment of oxygen toxicity and of pulmonary antioxidant defenses.

A regularity statistic for medical data analysis.

A new statistic has been developed to quantify the amount of regularity in data. This statistic, ApEn (approximate entropy), appears to have potential application throughout medicine, notably in electrocardiogram and related heart rate data analyses and in the analysis of endocrine hormone release pulsatility. The focus of this article is ApEn. We commence with a simple example of what we are trying to discern. We then discuss exact regularity statistics and practical difficulties of using them in data analysis. The mathematic formula development for ApEn concludes the Solution section. We next discuss the two key input requirements, followed by an account of a pilot study successfully applying ApEn to neonatal heart rate analysis. We conclude with the important topic of ApEn as a relative (not absolute) measure, potential applications, and some caveats about appropriate usage of ApEn. Appendix A provides example ApEn and entropy computations to develop intuition about these measures. Appendix B contains a Fortran program for computing ApEn. This article can be read from at least three viewpoints. The practitioner who wishes to use a "black box" to measure regularity should concentrate on the exact formula, choices for the two input variables, potential applications, and caveats about appropriate usage. The physician who wishes to apply ApEn to heart rate analysis should particularly note the pilot study discussion. The more mathematically inclined reader will benefit from discussions of the relative (comparative) property of ApEn and from Appendix A.

A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience.

Records have been kept prospectively in our institution since 1928 of all positive blood cultures taken from neonates. Using a modification of objective Centers for Disease Control criteria to define sepsis, we reviewed the records of all neonates with positive blood cultures for the years 1979 to 1988 inclusive and found 270 cases of sepsis. The sepsis rate for infants less than or equal to 30 days of age was 2.7 cases/1000 live births, with a mortality rate from sepsis of 15.9%. There was an increase in sepsis due to commensal species (CS) over the period (P less than 0.007). The number of infants in the nursery who developed sepsis when more than 30 days of age also increased (P less than 0.002), as did the rate of sepsis from CS in this group (P less than 0.001). Isolation of CS from the blood with fulfillment of the modified Centers for Disease Control criteria was associated with a 13.7% mortality rate, whereas isolation of CS without fulfillment was associated with a 4% rate (P less than 0.01).

Effect of artificial surfactant on pulmonary function in preterm and full-term lambs.

We hypothesized that agents very different from surfactant may still support lung function. To test this hypothesis, we instilled FC-100, a fluorocarbon, and Tween 20, a detergent, which have higher minimum surface tensions and less hysteresis than surfactant, into 15 full-term and 14 preterm lambs. FC-100 and Tween 20 were as efficient as natural surfactant in improving gas exchange and compliance in preterm lambs with respiratory failure. Dynamic compliance correlated with the equilibrium surface tension of the alveolar wash in both full-term (P less than 0.02) and preterm (P less than 0.008) lambs. Functional residual capacity in full-term and preterm lambs was lower after treatment with the two test agents than with surfactant, findings consistent with qualitative histology. Oxygenation in full-term lambs correlated with mean lung volumes (P less than 0.003), suggesting that the hysteresis and/or low minimum surface tension of surfactant may improve mean lung volume, and hence oxygenation, by maintaining functional residual capacity. The effects of the test agents suggest that agents with biophysical properties different from surfactant may still aid lung expansion.

Pulmonary function tests and fluid balance in neonates with chronic lung disease during dexamethasone treatment.

Pulmonary function tests and fluid balance were measured serially during treatment with dexamethasone in seven ventilator-dependent, 14- to 27-day-old infants. The infants showed no improvement in respiratory status during the prior 5 days. Birth weights ranged from 540 to 900 g, with gestational ages of 24 to 26 weeks. The decision to treat the infants with dexamethasone was made by the clinical team. Pulmonary function tests were performed prior to the first dose and then every 12 hours until extubation. Significant differences were first seen after only 12 hours of treatment. Five infants were extubated within 48 hours of starting therapy. Before extubation at 48 hours, changes were found in dynamic compliance (74% increase), total pulmonary resistance by midvolume and regression methods (38% and 35% decreases, respectively), and expiratory time constant (49% increase), with P less than .01 in all cases. An increase in urine output was also observed in the first 12 hours. Improvements in chronic lung disease produced by dexamethasone are rapid and may result from dexamethasone-induced pulmonary fluid shifts.

Antenatal steroids, postnatal surfactant, and pulmonary function in premature rabbits.

Antenatal corticosteroids reduce the incidence of the respiratory distress syndrome and improve pulmonary mechanics at least in part by mechanisms other than surfactant stimulation. We measured several aspects of pulmonary function in rabbits to better understand the mechanisms involved. Seven does were given intramuscular betamethasone and six were given vehicle on days 25 and 26 of gestation. Delivery was on day 27 (term = 31). Half of the fetuses from each litter were given rabbit surfactant before the first breath. All fetuses were then ventilated at a consistent tidal volume for 1 h. Pulmonary function tests included static and dynamic compliance, expiratory time constant, stress relaxation, total lung resistance, and total lung conductance. Steroid or surfactant treatment increased dynamic compliance, and the effects of both together were greater than either alone. Static compliance was affected more by surfactant than steroids, whereas lung resistance and conductance were affected more by steroids. The differences in action of the two therapies help account for the increased dynamic compliance seen with combination therapy.

Randomized study of six umbilical cord care regimens. Comparing length of attachment, microbial control, and satisfaction.

Two hundred and seventy one infants were enrolled in a study to compare six different methods of treating the umbilical cord. Antimicrobial control was equal for all methods. Repeated triple dye application was considered least acceptable by staff and parents and had the longest attachment time. Povidone-iodine was associated with the shortest attachment time and was most liked. If there is no special need to treat a specific nosocomial outbreak, duration of cord attachment and satisfaction of staff and parents can help clinicians decide on a cord care regimen.

A new syndrome with features of the Smith-Lemli-Opitz and Meckel-Gruber syndromes in a sibship with cerebellar defects.

The Smith-Lemli-Opitz syndrome (SLOS) and the Meckel syndrome (MS) have been regarded as separate autosomal recessive entities. Recently, overlap of these two syndromes has been discussed. A sibship containing a probable new syndrome with features reminiscent of the SLOS and the MS is presented. The literature is reviewed with regard to the frequency of various malformations in these syndromes. Clinical manifestations and cerebellar abnormalities in these sibs are similar to those described in the Joubert syndrome (JS). These three cases may represent a new syndrome with features in common with SLOS, MS, and JS resulting from the same mutant gene, which exhibits considerable pleiotropy.