Norihisa Koyama

Phenotypic Spectrum of COL4A1 Mutations: Porencephaly to Schizencephaly

Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations.

Effect of surfactant lavage in a rabbit model of meconium aspiration syndrome

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in neonates. Recent reports have suggested that surfactant dysfunction contributes to the pathophysiology of MAS and surfactant therapy improves oxygenation of infants with MAS. We evaluated the effect of bronchial lavage with surfactant solution in a rabbit model of meconium aspiration. All animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and mechanically ventilated. The animals were then divided into saline lavage (n = 5) or surfactant lavage (n = 5). Lavage was performed an hour after meconium instillation. After the lavage the total amount of meconium recovered was measured. Blood gas was monitored during the experiment. The amount of meconium recovered by saline lavage was 14%, and by surfactant lavage was 57%. The surfactant group had a significant improvement in gas exchange, whereas the saline group had no improvement. It was concluded that the lavage with surfactant solution effectively washed out meconium and improved gas exchange in rabbit model of MAS.

Management of meconium-related ileus in very low-birthweight infants

Background: Although administration of a water‐soluble contrast enema has been recognized to be effective for meconium‐related ileus, there have been no definitive management guidelines for very low‐birthweight infants.

Neurodevelopmental Outcomes at 18 Months’ Corrected Age of Infants Born at 22 Weeks of Gestation

Background: Increased survival rates for extremely low birth weight infants have been reported. However, survival rates and prognoses of extremely preterm infants, such as infants born at 22 weeks of gestation, are still poor. Objective: To investigate such infants’ long-term outcomes, developmental assessments were performed. Methods: Seven infants with gestational age of 22 weeks were delivered in our hospital from 2005 to 2008. One infant was a stillbirth despite resuscitation in the delivery room. Six infants, 4 boys and 2 girls, with a gestational age of 22 weeks (range 223/7–226/7 weeks), were admitted to the neonatal intensive care unit (NICU). Birth weights ranged from 514 to 710 g. None of the infants suffered from sepsis, necrotizing enterocolitis, or severe intraventricular hemorrhage. Results:The survival rate was 85.7% (6/7) as a percentage of deliveries and 100% (6/6) as a percentage of NICU admissions. None of the infants suffered from deafness, blindness, cerebral palsy, or epilepsy. Six infants were available for developmental assessments at 18 months’ corrected age. Three infants showed normal developmental quotients, and 3 infants showed developmental delay. Conclusion: In our study, all infants admitted to the NICU at a gestational age of 22 weeks were discharged from the hospital alive. This might suggest that infants after 22 weeks’ gestation be considered eligible for active treatment in Japan, though considering the size of the material, generalizibility of the results cannot be considered guaranteed.

Late-onset circulatory dysfunction of premature infants and late-onset periventricular leukomalacia

Background: The sudden appearance of hypotension and oliguria without obvious cause following stable circulation and respiration in preterm infants is frequent in Japan. Such episodes are referred to as late‐onset circulatory dysfunction of premature infants (LCD). Volume expanders and inotropic agents are often ineffective against this condition, whereas i.v. steroids are significantly effective. A major problem is that cystic periventricular leukomalacia (PVL) often develops a few weeks after an episode. The aim of the present study was to clarify the risk factors, including LCD, related to cystic PVL.

Carnitine-Associated Encephalopathy Caused by Long-term Treatment With an Antibiotic Containing Pivalic Acid

An 18-month-old boy was treated with an antibiotic containing pivalic acid for 6 months for intractable otitis media and then developed repeated convulsions and loss of consciousness. Laboratory data showed hypoglycemia and hypocarnitinemia. Intravenous administration of glucose was ineffective against the seizures and loss of consciousness. However, the patient regained consciousness and recovered soon after intravenous infusion of carnitine. To our knowledge, intravenous carnitine administration that contributed to marked improvements in neurologic deficit caused by administration of an antibiotic containing pivalic acid has not been reported previously. These findings indicate that long-term use of such antibiotics should be avoided.

Increased platelet activating factor in the tracheal aspirates from neonates with patent ductus arteriosus

We investigated platelet-activating factor (PAF) in the tracheal aspirate from 3 intubated low birth weight infants with symptomatic patent ductus arteriosus (PDA). PAF increased with the onset of symptomatic PDA and decreased to the control range soon after the ductal closure. The concentration of PAF in 26 samples taken during symptomatic PDA (median 16 pg/micrograms lipid phosphorus, range 1.4-1,200 pg/micrograms lipid phosphorus) was significantly higher than that of 31 samples from the same three patients during the periods without symptomatic PDA (median 1.9 pg/micrograms lipid phosphorus, range 0-12 pg/micrograms lipid phosphorus; P < 0.001). All 3 infants later developed chronic lung disease. These results suggest that large shunting PDA provokes PAF release to the air way of the neonate and that PAF might play a role in chronic lung disease developing after symptomatic PDA.

A case of systemic aplasia cutis congenita: a newly recognized syndrome?

Aplasia cutis congenita, congenital absence of a localized area of skin, usually on the vertex of the scalp, occurs as an isolated defect, or with one or more other congenital anomalies as part of a syndrome, sequence or association. To date, more than 500 cases have been reported. A more severe and extensive form, almost complete absence of skin and subcutaneous tissue, was reported by Park et al. in 1998 [J Med Genet 35:609–611]. Until now, no other such lethal case has been reported. Here, we report the second case of systemic aplasia cutis congenita. The female was born without any skin at all, and with hypoplastic lungs, syndactyly, skull defect, esophageal atresia, intestinal malrotation, and calcifications of the hepatic capsule, as well as with other anomalies. She died about 12 hours after birth probably due to dehydration. On microscopic examination, the external surface of the body showed complete absence of the epidermis. Muscle fibers were thin. There was no evidence of skin appendages. The present case gives strong support to the suggestion that systemic aplasia cutis congenita is a newly recognized syndrome. More cases will have to be reported and studied in order to understand the etiology and establish diagnostic criteria. Thus, it is our conclusion that systemic aplasia cutis congenita might be a newly recognized syndrome.

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

Abstract To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema.

Neuropathology of infant with Pena-Shokeir I syndrome

In an infant with clinical features of Pena-Shokeir I syndrome, who survived for 182 days, neuropathologic examination revealed little myelination in peripheral nerves with group atrophy of muscle fibers, dysplasia of inferior olivary and dentate nuclei, and leptomeningeal heterotopia. Congenital peripheral neuropathy associated with minor brain anomalies is characteristic in this patient, and may cause absence of fetal movements leading to ankylosis of multiple joints, absence of breathing in association with pulmonary hypoplasia, absence of swallowing causing polyhydramnios, and absence of movements of facial muscles causing craniofacial anomalies.