Keisuke Tokieda

Pulmonary dysfunction in neonatal SP-B-deficient mice

Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B +/+ and SP-B+/- mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/- mice, lung volumes and compliances were decreased markedly in homozygous SP-B-/- mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B-/- mice and was reduced in the SP-B+/- mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/- and SP-B-/- mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B-/- mice and in reduced lung compliance in SP-B+/+ and SP-B+/- mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B+/+ and SP-B+/- mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/- mice, lung volumes and compliances were decreased markedly in homozygous SP-B-/- mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B-/- mice and was reduced in the SP-B+/- mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/- and SP-B-/- mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B-/- mice and in reduced lung compliance in SP-B+/+ and SP-B+/- mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.

Surfactant protein B corrects oxygen-induced pulmonary dysfunction in heterozygous surfactant protein B-deficient mice.

Surfactant protein B (SP-B) is a 79-amino acid hydrophobic surfactant protein that plays a critical role in postnatal lung function. Homozygous SP-B (−/−)-deficient mice die of respiratory failure at birth, associated with severe pulmonary dysfunction and atelectasis. Heterozygous SP-B (+/−)-deficient mice have 50% less SP-B protein, proprotein, and SP-B mRNA compared with control mice and are highly susceptible to oxygen-induced lung injury. In the current study, we tested whether the susceptibility of SP-B (+/−) mice to hyperoxia was restored by intratracheal administration of exogenous SP-B. After exposure to 95% oxygen for 3 d, opening pressures were increased and maximal lung volumes were significantly decreased in SP-B (+/−) mice compared with SP-B (+/+) mice. SP-B (+/−) mice were administered purified bovine SP-B (2%) with DL-α dipalmitoyl phosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) phospholipids or DPPC and POPG phospholipids intratracheally and exposed to 95% oxygen. SP-B–treated SP-B (+/−) mice survived longer in 95% oxygen. Although decreased lung function in SP-B (+/−) mice exposed to oxygen was not altered by administration of DPPC and POPG, administration of lipids containing 2% purified bovine SP-B restored lung function when assessed after 3 d in oxygen. Abnormalities in pulmonary function in SP-B (+/−) mice after oxygen exposure were associated with increased alveolar capillary leak, which was corrected by administration of SP-B with DPPC and POPG. Likewise, histologic abnormalities caused by oxygen-induced lung injury were improved by administration of SP-B with DPPC and POPG. Administration of phospholipids with the active SP-B peptide was sufficient to restore pulmonary function and prevent alveolar capillary leak after oxygen exposure, demonstrating the protective role of SP-B during oxygen-induced lung injury.

Clinical manifestations of Bacillus cereus meningitis in newborn infants.

Abstract: Bacillus cereus (B. cereus) meningitis sometimes occurs in patients with risk factors, which are associated with central nervous system (CNS) anomalies, surgical or anaesthetic access to CNS. We observed two cases of B. cereus meningitis in neonates without such risk factors. The clinical courses of both neonates were fulminant, and routine antibiotic therapy failed. Intracranial haemorrhage was evident at autopsy. According to the previous neonatal case reports and our experience, we found that six of seven neonates were premature babies admitted to the neonatal intensive care unit, five died within a week of onset of the disease, and six had intracranial haemorrhage. We speculate that B. cereus meningitis may occur in neonates, even without any of the risk factors previously described in adult case reports, and that the clinical manifestations of the meningitis might be chjpccterized by the high incidence of intracranial haemorrhage and poor mortality.

Intrauterine MRI with single-shot fast-spin echo imaging showed different signal intensities in hypoplastic lungs.

Abstract Ultrasonography is used for the prenatal diagnosis of hypoplastic lungs. However, ultrasound poses problems because of difficulties in getting the entire lung in perspective and the results depend on the skill of the examiner. When the alveolar formation of the fetal lung is retarded, the fetus is predicted to show an altered density on MRI using an SSFSE sequence due to a varied amount of alveolar lung fluid. We present a case of twins who showed a marked difference in signal intensity of the lung on MRI, which was useful for predicting the fetal pathophysiology. Intrauterine MRI provides the possibility of diagnosing hypoplastic lungs prenatally.

A congenital anterior diaphragmatic hernia with massive pericardial effusion requiring neither emergency pericardiocentesis nor operation. A case report and review of the literature.

Abstract All previously reported cases of anterior diaphragmatic hernia with massive pericardial effusion were treated by pericardiocentesis and radical surgery during the early neonatal period. However, we initially followed the course of our patient in the neonatal period. Subsequently, elective surgery was performed at 70 days of age. Including our case, cardiac tamponade has not been observed in any previously reported cases of congenital anterior diaphragmatic hernia with massive pericardial effusion. Conclusion: Emergency pericardiocentesis and surgery are not always required immediately after birth, even when the presence of this condition is suspected by prenatal diagnosis. Our observation may be beneficial to preterm low birth weight infants with this condition.

An ultra premature baby of 290 g birth weight needed more than 500 mg/kg of calcium and phosphorus daily

Ultrapremature babies accompanied by intrauterine growth retardation may require supplemental calcium and phosphorus far above the recommended doses.

Intratracheal instillation of perfluorocarbon rescued mice with primary pulmonary hypoplasia

The aim of this study was to investigate the effect of perfluorocarbon on the respiratory status of newborn mice with pulmonary hypoplasia without diaphragmatic defects, following intrauterine exposure to nitrofen. Three groups of newborn mice were compared: pups exposed to nitrofen antenatally without (group A) or with (group B) perfluorocarbon treatment and pups not exposed to nitrofen as a control (group C). Respiratory evaluation was performed by scoring, pressure-volume analysis, and histological examination. At 40 minutes after birth, the survival rates in groups A, B, and C were 51%, 94%, and 95%, respectively. The clinical scores of group B mice at 40 minutes were significantly better than those of group A mice in which pulmonary hypoplasia was induced. In group B, the hysteresis ratio was significantly higher than that in group A, and lung histology showed a significant increase in airspace. An immunohistochemical examination showed that perfluorocarbon did not alter the expression of mature surfactant protein B and surfactant proprotein C. This study demonstrated that treatment with perfluorocarbon was useful in stabilizing critically ill mice with primary pulmonary hypoplasia during the early phase of therapy.