[Pharmacological prophylaxis and treatment of bronchopulmonary dysplasia]. / Medikamentöse Prophylaxe und Therapie der bronchopulmonalen Dysplasie.

Treatment with prenatal steroids, prophylactic or early therapeutic surfactant substitution, application of early nasal CPAP, minimizing of mechanical ventilation, early treatment of PDA and avoiding nosocomial infections are the main measures to prevent the development of bronchopulmonary dysplasia (BPD) in high-risk pre-term neonates. Beside these strategies, several pharmacologic interventions to prevent or to treat BPD have been investigated. So far, clear evidence for effective prevention has only been demonstrated for the administration of vitamin A and vaccinations. The administration of oxygen is the only effective treatment modality. Unfortunately, the upper and lower limits for the dosage of oxygen are still not clear. In patients with established BPD, a transient therapeutic effect is observed following treatment with systemic diuretics, inhaled steroids, and inhaled bronchodilators. However, treatment with these drugs has no documented long-term effect on the course of the disease. Systemic steroids only play a role as rescue treatment in life-threatening situations. Treatment with inhaled or systemic pulmonary vasodilatative may have a place in the treatment of pulmonary hypertension in severely affected infants. However, long-term experience in this treatment modality is still lacking.

[Perinatal glucocorticosteroid therapy: time for reconsideration]. / Die perinatale Therapie mit Glukokortikosteroiden: Zeit zum Umdenken1.

Glucocorticosteroids are administered antenatally and postnatally to decrease pulmonary morbidity of preterm neonates. One course of antenatal corticosteroids decreases mortality, and the frequency of respiratory distress syndrome and intraventricular hemorrhage. However, multiple courses may be associated with impaired brain development. Follow-up studies are needed to assess long-term consequences. The use of betamethasone may be of advantage compared to dexamethasone. Postnatally, steroids are given to treat or prevent bronchopulmonary dysplasia (BPD). However, recent studies have shown that treatment with dexamethasone increases the rate of cerebral palsy in preterm infants. Postnatal treatment of BPD with steroids should be restricted to life-threatening situations.

Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression.

Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies. In some cases congenital PAP is associated with hereditary surfactant protein (SP)-B deficiency. To date, the molecular defect in the majority of patients with PAP has not been identified. In mice, PAP has been generated by targeted deletion of the genes for either the GM-CSF/IL-3/IL-5 receptor common beta chain (beta c) or GM-CSF. Here, we describe an expression defect of beta c in three of seven pediatric patients with PAP and in one patient with severe lung disease suspected to be PAP. The patients failed to express normal levels of beta c as shown by flow cytometry. Strikingly reduced or absent function of beta c was demonstrated by ligand binding studies and progenitor clonogenic assays. Analysis of beta c DNA revealed a point mutation from proline to threonine at codon 602 in one patient. Our findings provide evidence that a defect in the expression of a hematopoietic cytokine receptor is associated with human PAP.

Improvement of oxygenation induced by aerosolized prostacyclin in a preterm infant with persistent pulmonary hypertension of the newborn.

OBJECTIVE: Case report on the effect of inhaled prostacyclin in a preterm infant (28 weeks gestational age) with respiratory distress syndrome complicated by marked hypoxemia due to persistent pulmonary hypertension of the newborn. Treatment with surfactant, hyperventilation, and elevation of systemic blood pressure had failed to improve oxygenation. MEASURES: A solution containing 10 micrograms PGI2/ml was aerosolized by the SPAG-2 aerosol-generator and then introduced into the afferent loop of the ventilatory circuit. RESULTS: Oxygenation improved dramatically and worsened when aerosolization was withdrawn. Intravenous prostacyclin had no additional effect on oxygenation. We observed no side effects on blood pressure and no bleeding complications. Inhalation was stopped after 40 hours and the baby was successfully weaned from the ventilator after 108 hours. CONCLUSION: Inhaled PGI2 had a beneficial effect on the oxygenation of a preterm neonate with persistent pulmonary hypertension of the newborn.

[Pathogenesis of bronchopulmonary dysplasia]. / Die Pathogenese der bronchopulmonalen Dysplasie.

Bronchopulmonary dysplasia of preterm infants has a multifactorial etiology. Pulmonary immaturity, oxygen toxicity, formation of oxygen radicals and mechanical lung trauma as well as additional factors (pulmonary hyperhydration, infection a.o.) may contribute to pulmonary damage. A pulmonary inflammatory reaction is thought to play a central role in the pathogenesis of chronic lung disease. It is characterized by the presence of inflammatory cells and various inflammatory mediators including proteases, chemoattractants, cytokines, leukotrienes and others. Due to the immaturity of several protective systems (antiproteases, antioxidants, surfactant system) the inflammatory response seems to be aggravated. Moreover, the magnitude and persistence of inflammation may eventually lead to pulmonary fibrosis.

Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) of preterm neonates is associated with an increased recruitment of inflammatory cells into the airways. To evaluate further the role of inflammation in the pathogenesis of BPD, tracheobronchial aspirate fluid of neonates with birth weight < 1200 g (n = 59) was sequentially analyzed in a prospective study. METHODS: Tracheobronchial aspirate fluid was assessed for chemotactic activity, neutrophil cell count, concentrations of elastase-alpha 1-proteinase inhibitor and activity of free elastase, concentrations of chemoattractants (complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8), and albumin concentrations as well as alpha 1-proteinase inhibitor activity. The secretory component for immunoglobulin A was used as reference protein. Only specimens without evidence of microbiological colonization were studied. RESULTS: In neonates with prolonged respiratory disease (BPD-risk neonates, n = 24, fraction of inspired oxygen > or = 0.3 and/or peak inspiratory pressure > or = 16 cm H2O at day 10 postnatal age, birth weight 892 +/- 36 g, gestational age 27.2 +/- 0.3 weeks) chemotactic activity, cell count, concentrations of the chemoattractants complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8, as well as levels of elastase-alpha 1-proteinase inhibitor were significantly higher at day 10 and/or day 15 of postnatal age compared with neonates without chronic pulmonary disease (total n = 35; day 10, n = 11; day 15, n = 8). There was no difference in free elastolytic activity. Concentrations of albumin as well as alpha 1-proteinase inhibitor activity were higher in BPD-risk patients on day 15, indicating an increased pulmonary leak. CONCLUSION: We conclude that preterm neonates at risk for the development of BPD show an enhanced inflammatory reaction in the lungs and an associated increase in pulmonary microvascular permeability. We speculate that inflammation may play an important role in the pathogenesis of BPD.

[Secondary myocardial hypertrophy in a very small premature infant treated with dexamethasone]. / Sekundäre Myokardhypertrophie bei sehr kleinen Frühgeborenen unter Dexamethasontherapie.

BACKGROUND: There is an increasing number of reports about the use of dexamethasone in the treatment of preterm infants at high risk for bronchopulmonary dysplasia. The possibility of myocardial hypertrophy developing during this treatment has not been examined. METHODS: As an example the course of one patient is described. We examined seven preterm infants (mean birth weight 791 g, mean gestational age 26 weeks) with eight treatments of dexamethasone retrospectively. The therapy was associated with a significant increase of the mean thickness of the interventricular septum and of the left ventricular posterior wall. After the termination of dexamethasone therapy the abnormal echocardiographic findings disappeared. CONCLUSION: We suggest careful monitoring of preterm infants treated with dexamethasone by performing serial echocardiographic investigations.

[Ureaplasma urealyticum--a new problem pathogen in neonatology]. / Ureaplasma urealyticum--ein neuer Problemkeim in der Neonatologie.

Some previous studies showed that Ureaplasma urealyticum is the most common germ that appears in the birthway of pregnant women and which is also frequently found in skin swabs and secretions of newborn and premature babies. The colonization of pregnant women by Ureaplasma urealyticum makes a premature birth more likely. Another factor of risk for a premature infant is a premature rupture of membranes for more than 24 hours which also makes an infection possible. There exists an association between pulmonary infection by Ureaplasma urealyticum and the development of a bronchopulmonary dysplasia especially for premature babies. According to our observations acute exacerbations of severe pneumonia can appear even after month. An attempt of therapy of pulmonary infection should be undertaken with erythromycin, if sensitive serotypes are present. In the case of erythromycin resistance chloramphenicol can be used but only under frequent controls of blood levels. We were able to observe rapid improvements with this effective therapy.

Quantitative aspects of transplantation of experimentally induced tumors of the nervous system.

Quantitative aspects of transplantation have been studied experimentally in ethylnitrosourea-induced nervous system tumors. The number of cells needed for successful transplantation, the biological behaviour-increase of malignancy-of the tumor in relation to the number of cells used during the various passages, and the relationship between number of grafted cells and induction time have been examined. A "critical" number of cells was necessary to ensure a positive result; thereafter, the induction time was directly related to the logarithm of the number of cells implanted.