Taihei Tanaka

Prenatal Diagnosis of Lissencephaly (Type II) by Ultrasound and Fast Magnetic Resonance Imaging

We report a case of lissencephaly which could be diagnosed by detailed examination during pregnancy. We first found bilateral enlarged ventricles in the fetus by routine abdominal ultrasonography at mid-pregnancy. Fast scanning MRI subsequently allowed confirmation of a diagnosis of lissencephaly during pregnancy.

Development and characterization of a novel porcine model of neonatal sepsis.

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 ± 3 mmHg in sepsis vs. 64 ± 3 mmHg in control at 3 h, 38 ± 7 mmHg in sepsis vs. 59 ± 4 mmHg in control at 6 h, mean ± SEM). They also showed an increase of serum levels of endotoxin (5.6 × 105 ± 4.5 × 105 pg/mL in sepsis vs. 6.0 × 102 ± 3.8 × 102 pg/mL in control at 6 h). Serum levels of TNF-α in the animals with sepsis became significantly higher than the control animals at 0 h (96 ± 31 pg/mL in sepsis vs. 12 ± 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 ± 231 pg/mL in sepsis in its peak at 6 h vs. 24 ± 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.

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.

Reduction of Pleural Effusion by OK-432 in a Fetus Complicated with Congenital Hydrothorax

A 29-year-old, primiparous woman was referred to our hospital at 21 weeks of gestation because of right pleural effusion in the fetus shown by routine ultrasonographic examination. Cytology revealed abundant lymphocytes, suggesting chylothorax. We removed the pleural effusion and injected OK-432 into the chest cavity at 24 and 25 weeks of gestation. Pleural effusion declined and an adhesion between the lung surface and the pleural membrane seemed to form. At 33 weeks of gestation, a female infant was born by cesarean section (1,090 g and Apgar score 6/8). Although she demonstrated slight retraction and tachypnea, management could be achieved by administration of oxygen alone without mechanical ventilation. Later, the baby was diagnosed as suffering from the Cornelia de Lange syndrome with characteristic features. OK-432 injections could thus prevent complications of chylothorax and hypoplastic lungs, without injury to either the baby or the mother.

The sex differences of cerebrospinal fluid levels of interleukin 8 and antioxidants in asphyxiated newborns.

Newborn males are more sensitive to brain injury than newborn females are. The aim of the present study was to find an explanation for this. We used the neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF) for the classification of 32 newborns (19 males and 13 females) on their fifth postnatal day. The NSE levels were higher than normal (8.4 ± 1.6 ng/mL) in 10 newborn males and 6 females and were, respectively, considered asphyxiated male and female groups. The remaining newborns, 9 males and 7 females, had normal CSF levels of NSE and were considered normal newborn male and female groups. The CSF samples were measured for 12 cytokines, using a cytokine array kit, and for total hydroperoxide and biological antioxidant potentials (BAPs), using the free radical analytic system. Among the 12 cytokines measured, only interleukin 8 (IL-8) was properly detected. The CSF levels of IL-8 were higher in the asphyxiated newborn females than in the other three groups. The mean CSF levels of BAPs in the asphyxiated newborn females were higher compared with the other three groups, but significance was detected only in comparison with the BAP levels in the CSF samples of the normal newborn males. There were no differences in total hydroperoxide levels among the groups. There are sex-related differences in the CSF levels of IL-8 and antioxidants in asphyxiated newborns, with higher levels in newborn females; this might contribute in the sexual dimorphism regarding the fact that females have better protection from brain injury than the males.

Nitric oxide further attenuates pulmonary hypertension in magnesium-treated piglets

Background : Persistent pulmonary hypertension of the newborn (PPHN) commonly appears as a complication of several pulmonary and non‐pulmonary diseases. The hypoxia possibly inhibits Ca2+ ± dependent K+ channels, thus resulting in membrane depolarization of pulmonary smooth muscle cells, which leads to the opening of Ca2+ channels and Ca2+ entry, resulting in contraction of the vascular smooth muscle. However, magnesium (Mg2+) is an antagonist of Ca2+. We studied the effect of magnesium sulfate on the treatment of hypoxia‐induced pulmonary hypertension and compared to the site of action of nitric oxide (NO).

Prognostic factors of hydrops fetalis with pleural effusion

Hydrops fetalis (HF) has a low survival rate, particularly in the case of preterm birth. In addition, the severity index of HF has not been fully investigated yet. The aim of this study was to clarify the prognostic factors of HF with pleural effusion.

clinical features of late-onset circulatory dysfunction in premature infants

Background: Sudden unpredictable hypotension during the post-transitional period, termed late-onset circulatory dysfunction (LCD) of premature infants, has been reported in low birthweight infants who overcame major problems during the early neonatal period. We investigated the clinical features of LCD and factors associated with the occurrence of LCD. Methods: A multicenter retrospective case-control study. The clinical records of 1,004 children born at less than 32 weeks of gestation were reviewed. Patients with LCD were compared with age-matched non-LCD controls. Results: Of the 1,004 infants, 73 (7.3%) were diagnosed with LCD, with the incidence differing significantly among institutions ( P,0.0001). The median age of diagnosis was 16 days of age (range: 4–50 days) and 29 weeks of postmenstrual age (range: 25–35 weeks). The incidence of LCD was inversely correlated with gestational age at birth, except at 22 and 23 weeks. Compared with the control infants, the LCD infants had significantly higher incidences of birth by cesar ean section (61/73 versus 48/73, P,0.05); hyponatremia (sodium ,130 mEq/L) at the time of diagnosis (24/66 versus 3/39, P,0.01); deterioration of respiratory status within 24 hours before diagnosis (36/73 versus 6/73, P,0.0001); and periventricular leukomalacia (14/73 versus 4/73, P,0.05). Corticosteroids were effective in 52 infants who were unresponsive to volume expansion or inotropic agents. None of these infants died of LCD. Conclusion: LCD is common but worthy of attention due to its association with periventricular leukomalacia. A review of institutional differences in treatment policies may contribute to the prevention of LCD.

Effects of the early administration of sivelestat sodium on bronchopulmonary dysplasia in infants: A retrospective cohort study

BACKGROUND Chorioamnionitis, or infiltration of the chorioamnion by neutrophils, is a risk factor associated with the development of bronchopulmonary dysplasia. Increased neutrophil elastase levels are observed in the tracheal aspirates of these patients. AIMS To examine the effects of early administration of the selective neutrophil elastase inhibitor sivelestat, which is used to treat acute lung injury in adults, on bronchopulmonary dysplasia in extremely premature infants. STUDY DESIGN Retrospective cohort study. SUBJECTS This study included extremely low-birth-weight infants born at a gestational age<28weeks. Patients were divided into groups based on the receipt of sivelestat. OUTCOME MEASURES The primary outcome was the rate of bronchopulmonary dysplasia-free survival at a postmenstrual age of 36weeks, and the secondary outcomes included various clinically significant factors of neonatal mortality and morbidity and adverse events. RESULTS Of the 1031 included neonates, 124 (12.0%) were treated with sivelestat. Significant differences between the groups were noted for gestational age, delivery method, fetal number, the frequency of chorioamnionitis, immunoglobulin M levels, and WBC counts. No differences were identified concerning the bronchopulmonary dysplasia-free survival rate at a postmenstrual age of 36weeks (adjusted odds ratio for sivelestat to control, 0.83; 95% confidence interval=0.53-1.30). Secondary outcomes did not significantly differ between the groups. CONCLUSIONS In extremely premature infants, early sivelestat use was not associated with an improved rate of survival without bronchopulmonary dysplasia at a postmenstrual age of 36weeks.