ABSTRACT
Two female sibling full-term newborns developed respiratory distress shortly after birth, which progressed to respiratory failure. Tracheal lavage demonstrated presence of surfactant protein A (SP-A), but little surfactant protein B (SP-B), without aberrant surfactant protein C (SP-C). On a lung biopsy performed in both infants, prominent type II pneumocyte hyperplasia was evident. Through ultrastructural examination an absence of normally formed lamellar bodies was determined, with numerous irregular electron dense bodies within the type II pneumocytes. These electron dense bodies could also be identified in the alveolar spaces and alveolar macrophages. No alveolar tubular myelin was present. Abnormally high immunoreactivity for surfactant proteins SP-A, proSP-B, SP-B, and proSP-C was demonstrated by light microscopy. Presence of incompletely processed immunopositive proSP-B, but not proSP-C was observed in the alveolar lumina. No mutations in either the SP-B or SP-C gene were identified by sequence analysis of amplified cDNA. We conclude that these siblings exhibit an inherited surfactant deficiency characterized by abnormal accumulations of surfactant proteins within the pneumocytes. This abnormal accumulation may be due to a primary secretory defect, a defect in surfactant phospholipids, or an abnormal interaction between the phospholipids and surfactant proteins.
Subject(s)
Pulmonary Surfactants/deficiency , Respiratory Distress Syndrome, Newborn/genetics , Bronchoalveolar Lavage Fluid/chemistry , DNA, Complementary/analysis , Female , Humans , Immunohistochemistry , Infant, Newborn , Lung/metabolism , Lung/pathology , Lung/ultrastructure , Macrophages, Alveolar/metabolism , Mutation , Nuclear Family , Pulmonary Surfactants/analysis , Pulmonary Surfactants/genetics , Respiratory Distress Syndrome, Newborn/pathologySubject(s)
Infant, Low Birth Weight , Infant, Premature, Diseases/mortality , Infant, Premature , Arkansas/epidemiology , Hospital Mortality , Humans , Infant , Infant Mortality , Infant, Newborn , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/therapy , Intensive Care, Neonatal , Survival RateSubject(s)
Infant, Newborn, Diseases/therapy , Resuscitation , Acid-Base Equilibrium , Apgar Score , Asphyxia Neonatorum/etiology , Asphyxia Neonatorum/therapy , Atropine/therapeutic use , Bicarbonates/therapeutic use , Blood Transfusion , Calcium Gluconate/therapeutic use , Epinephrine/therapeutic use , Female , Fetal Blood , Fetal Organ Maturity , Glucose/therapeutic use , Humans , Infant, Newborn , Intubation, Intratracheal , Isoproterenol/therapeutic use , Lung/embryology , Meconium , Narcotic Antagonists/therapeutic use , Pregnancy , Sodium BicarbonateABSTRACT
23 premature infants were placed on a randomized double-blind study to evaluate the effectiveness of indomethacin in closing a patent ductus arteriosus. Infants received 0.2 mg/kg indomethacin or placebo by gavage. In the treatment group, 7 patients responded out of a total of 12, while in the placebo group, 2 responded out of a total of 11. Indomethacin plasma levels were obtained in 6 patients in the treatment group. Plasma levels showed marked variability in peak level (60-3,100 ng/ml), time to peak level (0.5-6 h) and t1/2 (1 to greater than 24 h).
