Shoichi Chida

Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome

Background : Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low‐birth‐weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS.

Morphology and function of pulmonary surfactant inhibited by meconium

The pathophysiology of neonatal meconium aspiration syndrome (MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. It has also been suggested that meconium causes inhibition of surfactant function. To assess its in vitro effect on surfactant function and morphology, we used a pulsating bubble surfactometer to measure the dynamic surface tension of meconium-surfactant mixtures and observed their electron microscopic structures. The mixtures were prepared by adding serial dilutions of human meconium to various concentrations of Surfactant-TA(Surfacten™) that had been used for the prevention and treatment of neonatal respiratory distress syndrome. Inhibition of the surface tension-lowering properties of Surfactant-TA was caused by the addition of meconium and depended on the concentration of the surfactant; the inhibition could be overcome by increasing the surfactant concentration. When meconium was added to Surfactant-TA, the characteristic ultrastructural features of the latter, the loosely stacked layers, changed to a spherical lamellar structure and folded linear structures. These results suggest that meconium inhibits surfactant function by altering surfactant morphology. Our morphologic and functional findings support the new concept that surfactant inhibition may play a role in the pathophysiology of MAS.

Stable microbubble test for predicting the risk of respiratory distress syndrome: II. Prospective evaluation of the test on amniotic fluid and gastric aspirate

We determined prospectively if the stable microbubble (SM) test on gastric aspirate obtained at birth was as useful as that on amniotic fluid in predicting respiratory distress syndrome (RDS). One hundred and five paired samples of amniotic fluid obtained at delivery from 105 consecutive women with gestation of 35 weeks or less and gastric aspirates from their neonates obtained within 30 min of birth were studied. The SM test with the predefined cut-off value of less than 5 bubbles/mm2 for amniotic fluid and less than 10 bubbles/mm2 for gastric aspirate signified the risk of RDS with the positive predictive value of 100% and 96% and with the negative predictive value of 91% and 84%, respectively. We conclude that the SM test on both amniotic fluid and gastric aspirate obtained at birth is a rapid (<10 min), simple and reliable procedure for predicting neonates who will develop RDS. It may be used as a bedside test to define a population of neonates with surfactant deficiency in clinical trials of prophylactic surfactant therapy.

A prospective, randomized trial of early versus late administration of a single dose of surfactant-TA

Thirty-two neonates weighing 500-1500 g with documented surfactant deficiency and without evidence of severe birth asphyxia, infection, prolonged rupture of membranes greater than or equal to 72 h, or oligohydramnios were randomly assigned to receive a single intratracheal dose of surfactant-TA (100 mg/kg) either within 30 min of birth (n = 16, early group) or at 6 h of age (n = 16, late group). By 6 h of age, all neonates of the late group had moderate/severe RDS, while none of the neonates of the early group had either clinical or radiological respiratory distress syndrome. The incidence of bronchopulmonary dysplasia was significantly lower in survivors of the early group than those of the late group (1/15 versus 7/14, a 43% reduction with a 95% confidence interval of 14-72%, P = 0.025). These beneficial effects of early surfactant treatment remained after controlling for the various confounding factors in the logistic models.

Transient decrease in cerebral white matter diffusivity on MR imaging in human herpes virus-6 encephalopathy

We report a 16-month-old boy with human herpes virus-6 (HHV-6) encephalopathy showing transient abnormalities of the cerebral white matter on magnetic resonance imaging. Diffusion-weighted imaging (DWI) demonstrated diffuse high signal intensity in the bilateral cerebral white matter areas. The signal changes on DWI subsequently resolved, and cerebral atrophy resulted. The transient decrease in the cerebral white matter diffusivity seen in the present case may reflect axonal involvement secondary to the glial or neuronal damage in HHV-6 encephalopathy.

Surfactant Replacement Therapy in Premature Babies with Respiratory Distress Syndrome: Factors Affecting the Response to Surfactant and Comparison of Outcome from 1982–86 and 1987–91

The impact of surfactant therapy on chronic lung disease remains uncertain. During the past decade (1982–91), over 300 babies with respiratory distress syndrome (RDS) weighing 501–2,500 g at birth were consecutively treated with surfactant‐TA at our neonatal intensive care unit. Data on 95 RDS babies treated in the first 5 year period (Period 1, 1982–86) were compared with those on 158 RDS babies treated in the second 5 year period (Period 2, 1987–91). Overall respiratory improvement was better in Period 2 than in Period 1. In Period 2, surfactant therapy converted 98% of the babies with moderate/severe RDS to those with ‘near normal’ lung by 72 hr post‐treatment. In Period 2, 95% of the surfactant‐treated babies weighing 501–1,750 g at birth survived, 97% of which required no supplemental oxygen at 40 weeks corrected gestational age. Increased survival rate in the surfactant‐treated babies during the past decade has not been followed by a parallel increase in chronic lung disease. The severity of the initial pulmonary disease per se was not the significant risk factor for chronic lung disease. Several other variables affecting the response to surfactant therapy and outcome have been identified by stepwise logistic regression analysis and include factors related to perinatal events such as birth asphyxia and infection, and other complications of prematurity.

A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.

Objectives: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated. Methods: We analyzed the patients’ genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed. Results: The analysis showed that the patients homozygously retained a missense mutation, GGC[435Gly]→AGC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced. Conclusion: These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450C18 activities causes CMO II deficiency.

Apoptotic epithelial cells in biopsy specimens from infants with streaked rectal bleeding

Background Histologic studies of rectosigmoidal mucosal biopsies of infants with isolated blood-streaked stool have shown many eosinophils and revealed aggregates of small dark granules (nuclear dust). However, no description of the nuclear dust has been made for this condition and the nature of the nuclear dust has not been thoroughly investigated. We determined the characteristics of these particles in biopsies from infants with streaked rectal bleeding. Methods Nineteen infants who were younger than 6 months old and had isolated rectal bleeding were studied, as were six age-matched control infants. Rectosigmoidal mucosal biopsies were immunohistochemically assessed using anticarcinoembryonic antigen and macrophage-associated antibodies and examined for apoptotic cells by modified in situ TdT-mediated dUTP-biotin nick-end labelling. The number of apoptotic epithelial cells was compared between rectal bleeding and control groups. Results Immunohistochemistry showed that at least some of the nuclear dust consisted of apoptotic epithelial cells. Infants with rectal bleeding also showed nodular lymphoid hyperplasia (n = 16), abundant eosinophils (>20/high power field, n = 14) in the mucosa, and a significantly high number of apoptotic epithelial cells relative to the control group. Rectal bleeding disappeared at 6-month follow-up in 14 of 18 infants (one was lost to follow-up) who were fed a different milk formula or breast-fed (their mothers were restricted from having cows milk and eggs). Conclusions The high number of apoptotic epithelial cells in rectosigmoidal mucosal biopsies of infants with streaked rectal bleeding is probably caused by accelerated epithelial cell turnover and apoptosis.

Precision and Reliability of Stable Microbubble Test as a Predictor of Respiratory Distress Syndrome

The precision and reliability of the stable microbubble test as a predictor of respiratory distress syndrome (RDS) were studied. In blind experiments, the stable microbubble test was performed by three analysts in quadruplicate on six different amniotic fluid samples obtained from pregnant women whose babies developed RDS and on three samples prepared from mature controls. Three‐way analysis of variance revealed that there were statistically significant differential effects of the analyst, observer, and sampling on the stable microbubble values, and also that there were statistically significant interactions between the analyst and observer as well as between the analyst and sampling. However, the magnitude of these effects was not large enough to modify the interpretation of the test results. We conclude that the rapidity, simplicity and reliability of the stable microbubble test allow for its use as a bedside procedure in identifying infants who are likely to develop RDS.

Infection surveillance after a natural disaster: lessons learnt from the Great East Japan Earthquake of 2011

PROBLEM On 11 March 2011, the Great East Japan Earthquake produced a catastrophic tsunami that devastated the city of Rikuzen-Takata and left it without an effective health infrastructure and at increased risk of outbreaks of disease. APPROACH On 2 May 2011, a disease-surveillance team was formed of volunteers who were clinicians or members of Rikuzen-Takatas municipal government. The teams main goal was to detect the early signs of disease outbreaks. LOCAL SETTING Seven weeks after the tsunami, 16 support teams were providing primary health care in Rikuzen-Takata but the chain of command between them was poor and 70% of the citys surviving citizens remained in evacuation centres. The communication tools that were available were generally inadequate. RELEVANT CHANGES The surveillance team collected data from the citys clinics by using a simple reporting form that could be completed without adding greatly to the workloads of clinicians. The summary findings were reported daily to clinics. The team also collaborated with public health nurses in rebuilding communication networks. Public health nurses alerted evacuation centres to epidemics of communicable disease. LESSONS LEARNT Modern health-care systems are highly vulnerable to the loss of advanced technological tools. The initiation--or re-establishment--of disease surveillance following a natural disaster can therefore prove challenging even in a developed country. Surveillance should be promptly initiated after a disaster by (i) developing a surveillance system that is tailored to the local setting, (ii) establishing a support team network, and (iii) integrating the resources that remain--or soon become--locally available.