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The pathogenesis of virus-associated acute encephalopathy (VAE) involves brain edema caused by disruption of the blood–brain barrier (BBB). We aimed to develop an in vitro VAE model using an in vitro BBB model, to evaluate the dynamics of vascular dysfunction caused by tumor necrosis factor (TNF)-α. A co-culture model, consisting of Transwell®-grown human brain microvascular endothelial cells and pericytes, was treated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using cellZscope®. A permeability assay, using fluorescein isothiocyanate-conjugated sodium or dextran, was performed. Changes in claudin-5 localization and expression after TNF-α treatment were observed using immunofluorescence staining and western blot analysis. The TER decreased and permeability increased after TNF-α treatment; recovery time was dependent on TNF-α concentration. Claudin-5 was delocalized after TNF-α treatment and recovered in a TNF-α concentration-dependent manner. The expression of claudin-5 decreased 24 h after the TNF-α treatment and completely recovered 48 h after TNF-α treatment. Claudin-5 delocalization was likely associated with vascular hyperpermeability. To conclude, we evaluated vascular endothelial cell permeability and injury in VAE using an in vitro BBB model treated with TNF-α. This system can be useful for developing novel therapeutic strategies for VAE and designing treatments that target vascular permeability.

Background During storage, the potassium level of red blood cell (RBC) components increases, especially after irradiation. Neonates are prone to hyperkalemia, for example, non-oliguric hyperkalemia, so using potassium adsorption filters during transfusion may be helpful. To overcome dilution of RBC components caused by saline priming of existing potassium adsorption filters, a downsized potassium adsorption filter for neonates (PAF-n, Kawasumi Laboratories Inc., Tokyo, Japan) was developed. Study design and methods To assess the performance of PAF-n, its adsorption efficiency and RBC recovery rate were evaluated by testing pre-filtration and serial post-filtration (0-30 mL, 30-60 mL, 60-90 mL, and 90-120 mL) samples from 8 RBC components. Results The average potassium adsorption rate of the PAF-n was 90.5% ± 0.78%, and never less than 89.0% in any of 8 RBC components. RBC recovery rates were 99.3% ± 1.12%. Conclusion The PAF-n showed an effective potassium ability with negligible RBC dilution.

Premature infants are often exposed to positive pressure ventilation and supplemental oxygen, which leads to the development of chronic lung disease (CLD). There are currently no standard serum biomarkers used for prediction or early detection of patients who go on to develop CLD. MicroRNAs (miRNAs) are a novel class of naturally occurring, short, noncoding substances that regulate gene expression at the posttranscriptional level and cause translational inhibition and/or mRNA degradation and present in body fluids packaged in extracellular vesicles (EVs), rendering them remarkably stable. Our aim was to evaluate miRNAs identified in serum EVs of premature infants as potential biomarkers for CLD. Serum EVs were extracted from premature infants at birth and on the 28th day of life (DOL). Using a human miRNA array, we identified 62 miRNAs that were universally expressed in CLD patients and non-CLD patients. Of the 62 miRNAs, 59 miRNAs and 44 miRNAs were differentially expressed on DOL0 and DOL28 in CLD and non-CLD patients, respectively. Of these miRNAs, serum EV miR-21 was upregulated in CLD patients on DOL28 compared with levels at birth and downregulated in non-CLD patients on DOL28 compared with levels at birth. In neonatal mice exposed to hyperoxia for 7days, as a model of CLD, five miRNAs (miR-34a, miR-21, miR-712, miR-682, and miR-221) were upregulated, and 7 miRNAs (miR-542–5p, miR-449a, miR-322, miR-190b, miR-153, miR-335–3p, miR-377) were downregulated. MiR-21 was detected as a common miRNA that changed in CLD patients and in the hyperoxia exposed mice. We conclude that EV miR-21 may be a biomarker of CLD.

Background: While breastfeeding provides both optimal nutrition for infants and health benefits for the mother, many women either do not breastfeed or terminate breastfeeding earlier than recommended. The aim of this analysis was to identify factors associated with early discontinuation of breastfeeding in Japanese women.Methods: This study utilized medical records from the Iwase General Hospital in Fukushima Prefecture, Japan to assess cessation of breastfeeding by the 1-month postpartum appointment. Demographic, medical, and family predictors among 734 women who had initiated breastfeeding during their delivery hospital stay were examined, and multiple logistic regression was used to determine significant predictors of early cessation of exclusive breastfeeding.Results: In a bivariate analysis, it was observed that women who were primipara, unmarried, smoked before pregnancy, were exposed to secondhand smoke, employed, and/or had asthma were more likely to discontinue exclusive breastfeeding. Infant factors associated with discontinuation were lower birthweight, earlier gestational age, neonatal intensive care unit admission, treatment for jaundice, or lower weight gain. In multivariable analysis, primiparity, smoking before pregnancy, maternal employment and neonatal jaundice therapy remained associated with discontinuation of breastfeeding.Conclusions: Several maternal factors are associated with discontinuation of exclusive breastfeeding. In particular, women who smoke before pregnancy may need to be targeted for additional support for breastfeeding.

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

Background Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy, associated with high morbidity and mortality, but the role of genetics in cases of fetal-onset has not been fully evaluated. The goal of this study was to identify the genetic background in LVNC fetal-onset patients using next-generation sequencing (NGS). Methods Thirty-three fetal-onset Japanese probands with LVNC (20 males and 13 females) were enrolled. In the enrolled patients, 81 genes associated with cardiomyopathy were screened using next-generation sequencing (NGS) retrospectively. Results Twenty-three patients had congestive heart failure (CHF), and six patients had arrhythmias. Prominent trabeculations were mostly observed in lateral LV, posterior LV, and apex of LV in patients with LVNC. Twelve died; three patients experienced intrauterine death or termination of pregnancy. Overall, 15 variants were found among eight genes in 16 patients. Seven variants were detected in MYH7 and two in TPM1. Sarcomere gene variants accounted for 75.0%. A multivariable proportional hazards model revealed that CHF at diagnosis and a higher ratio of the noncompacted layer/compacted layer in the LV posterior wall were independent risk factors for death in LVNC fetal-onset patients (odds ratio = 4.26 × 106 and 1.36 × 108, p = 0.0075 and 0.0005, respectively). Conclusions The present study is the first report focusing on genetic background combined with clinical features in LVNC fetal-onset patients using NGS. Sarcomere variants were most commonly identified in fetal-onset patients, and greater attention should be paid to fetal-onset patients with LVNC having prominent trabeculations in the LV because they are more likely to develop CHF.

Background: Platelets participate in many physiological and pathological functions and some platelet parameters predict adult diseases. However, few studies report whether platelet parameters may reflect neonatal disease and mortality in a large cohort.Objective: We aimed to investigate whether platelet parameters could predict bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and NICU mortality.Study Design and Methods: This retrospective cohort study examined records from 2006 to 2017 at the neonatal intensive care unit (NICU) of Fukushima Medical University Hospital. We retrospectively investigated platelet count, plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) on the first day of life in preterm newborns born

Background: We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants. Methods: We conducted a prospective study of extremely premature infants admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Fukushima City, Japan between January 2014 and December 2015. GB volume was measured by an abdominal ultrasound ellipsoid method between Day 0 and Day 56 after birth within 60 minutes before enteral feeding. We calculated GB volume (mL)/weight (kg), which was evaluated as GV/W. Results: In total, 30 infants were included. The median gestational age of the infants was 26 weeks 5 days (range, 23 weeks 1 day–28 weeks 6 days), and the median birth weight was 731 g (range, 398–1220 g). The detection rate of GB decreased in the infants over time; the rates were > 93% between Day 0 and Day 7 and < 77% between Day 10 and Day 56 after birth. GV/W decreased in the infants over time. The median GV/W values were 0.18 (range, 0.05–0.59) in infants on admission and constantly

Virus-associated acute encephalopathy (VAE) is a severe central nervous system complication caused by common viral infections in children. The pathophysiology of VAE is thought to be endothelial injury. This study was designed to establish an in vitro VAE model for evaluating endothelial injury caused by the proinflammatory cytokine TNF-α. Transwell-grown human umbilical vein endothelial cells (HUVECs) monolayers were incubated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using impedance spectroscopy. Permeability changes of HUVECs after TNF-α treatment were determined by fluorescein isothiocyanate (FITC)-conjugated dextran. Moreover, TNF-α-induced morphological changes in claudin-5 and apoptosis were observed by immunofluorescent staining. The decrease in TER, time of TER recovery to baseline, and increase in permeability were all dependent on TNF-α concentration. Immunofluorescent staining showed that claudin-5 was delocalized after TNF-α treatment in a dose-dependent manner. In addition, some apoptotic cells were observed at high TNF-α concentrations. TER measurement combined with a permeability assay could be useful for evaluating vascular endothelial cell permeability in an in vitro model. These evaluation methods will contribute to both the development of specific treatments focusing on vascular permeability, and the search for a novel therapeutic strategy in VAE treatment.

Congenital anomalies of the spine may occur with malformations of the central nervous, cardiovascular, gastrointestinal, respiratory, and genitourinary systems. This is a case of myelomeningocele with unilateral right renal agenesis in a newborn. The patient suffered complications of cerebrospinal fluid leak and meningitis, but was successfully treated and discharged on day 86. In this case, unilateral right renal agenesis represented a significant surgical risk because failure of the remaining kidney could result in renal failure. Because congenital anomalies of the spine may be associated with malformations of the genitourinary system, and additional surgeries were necessary in our case following birth, it is very important that the presence of genitourinary malformations be evaluated.

At 32 weeks of gestation, a male fetus with congenitally corrected transposition of the great arteries developed hydrops fetalis caused by a combination of mitral valve regurgitation and tricuspid valve regurgitation (TR). We performed a pulmonary artery banding (PAB) at 108 days old for gradually progressing TR, after confirming that a balloon dilatation test in the main pulmonary artery reduced TR. As the patient grew, the PAB became tighter and systolic blood pressure in the morphological left ventricle increased. At present, the patient is waiting for a double switch operation.

To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time–international normalized ratio correlated with intraventricular hemorrhage (p = 0.000; β = 0.180) and placental abruption (PA; p = 0.000; β = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p = 0.000; β = − 0.217), gestational age (GA; p = 0.000; β = − 0.282), and PA (p = 0.000; β = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome (p = 0.007; β = − 0.114), pregnancy-induced hypertension (p = 0.000; β = − 0.141), and Apgar score at 1 minute (p = 0.043; β = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes (p = 0.049). Finally, antithrombin III levels positively correlated with GA (p = 0.000) and BW (p = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates.

Infants with Down syndrome (DS) are at risk of developing a transient myeloproliferative disorder during the neonatal period, known as transient abnormal myelopoiesis (TAM). It is characterized by clonal myeloproliferation and is typically self-limiting. However, TAM can be a life-threatening disorder, when complicated by liver fibrosis. Here, we evaluated cytokine profiles in two male DS infants having TAM with or without liver dysfunction. The first patient, Patient 1, had hyperleukocytosis with cholestatic liver dysfunction, coagulopathy, and increased counts of blasts and was treated with exchange transfusion (ExT) due to the serious general condition. In Patient 1, serum interleukin (IL)-8 and plasma transforming growth factor (TGF)-β1 levels were markedly elevated before ExT (1,518.2 pg/mL and 17,635 pg/mL, respectively). After ExT, serum IL-8 and plasma TGF-β1 levels decreased to 40.7 pg/mL and 6,847 pg/mL, respectively. However, Patient 1 died on day 56 due to cholestatic liver dysfunction; namely, this patient represents fatal TAM. The second patient, Patient 2, had hyperleukocytosis with increased counts of blasts without liver dysfunction and was treated with cytarabine. In Patient 2, plasma TGF-β1 levels, but not plasma IL-8, were elevated (9,068 pg/mL and 28 pg/mL, respectively). Patient 2 was discharged on day 47. In summary, plasma TGF-β1 levels were elevated in the two DS infants with TAM, regardless of the presence or absence of hepatic fibrosis. Importantly, fatal TAM is assoicated with the elevated serum level of IL-8. We thus propose that IL-8 may be involved in the pathogenesis of liver fibrosis.

Background Wolf–Hirschhorn syndrome (WHS), which is characterized by a typical facial appearance, growth retardation, mental retardation, seizures, and congenital cardiac defects, has an estimated incidence of 1 per 50,000 births. Case We report a case of a low birth weight neonate with WHS and seizures, as well as persistent pulmonary hypertension in the early neonatal period. Apgar scores were 6 (1 minute) and 8 (5 minutes) with evident retraction. After admission to the neonatal intensive care unit, the patient had tonic–clonic seizures with epilepticus 30 minute after birth. Although the seizures were uncontrollable, continuous thiopental administration was effective for seizure mitigation. Conclusion Neonatal seizures with WHS occur rarely. This is the first case report on seizures just after birth in a neonate with WHS.

We investigated the relationship of neonatal and maternal serum creatinine (nSCr and mSCr, respectively) with various maternal/infant characteristics at different gestational ages (GA). We reviewed medical records of neonates admitted to NICU. We collected data on birth weight, GA, Apgar scores, medications, etc. Spearman’s test was used to analyze the correlation between serum creatinine and continuous variables, and the Mann-Whitney U and Kruskal-Wallis tests for continuous variables between groups. The changes in nSCr, mSCr, and nSCr/mSCr ratio because of gestational age and the points in gestational changes in trends were estimated using joinpoint trend analysis. From 614 neonate and mother pairs, we found that nSCr was significantly correlated with GA. However, mSCr at >28 wks decreased with GA. The nSCr/mSCr ratio was correlated with GA. In infants born

A 9-year-old girl developed influenza A H1N1 pdm09-associated myocarditis and pericarditis 2 days after starting zanamivir therapy. The virus was detected in the respiratory tract but not in the serum or pericardial effusion. The virus sampled from the respiratory tract had normal susceptibility to neuraminidase inhibitors. Although no differences in interferon-γ, interleukin (IL)-1β, and tumor necrosis factor-α were observed between the plasma and pericardial effusion, some inflammatory cytokines or chemokines (IL-6 and IL-8) and vascular endothelial growth factor were remarkably elevated in the pericardial effusion compared with the plasma. This suggested that the influenza virus, after infecting the respiratory tract, affected the myocardium, causing myocarditis to gradually develop, which might have been followed by an autoreactive pericarditis causing increased pericardial effusion. Therefore, influenza-associated myocarditis should be considered when influenza patients have respiratory and cardiac involvement, even during treatment with a neuraminidase inhibitor.

OBJECTIVE To investigate the relationships between serum cytokine concentrations and chorioamnionitis (CAM) and CAM-related bronchopulmonary dysplasia (BPD) in premature infants. METHODS Serum was collected at 0 and 7 days after birth from 36 premature infants born at

Minocycline pleurodesis was performed on five infants with congenital chylothorax in our institutions. They could not achieve sufficient efficacy though they had received other conservative therapies. Four of the five cases obtained reduction of pleural effusion using the minocycline pleurodesis. We concluded that minocycline pleurodesis is a safe and an effective technique for congenital chylothorax.

Aim We determined whether the bacteria in the lower respiratory tract (LRT) in extremely premature infants with severe bronchopulmonary dysplasia (BPD) are different from those with nonsevere BPD. Study Design We conducted a retrospective study of extremely premature infants who were admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Japan between April 2005 and March 2014. We screened for the bacterial colonization of the LRT using tracheobronchial aspirate fluid. Results A total of 169 extremely premature infants were included. Overall, 102 did not experience severe BPD, whereas the remaining 67 experienced severe BPD. Corynebacterium species (Cs) were more frequently detected in the severe BPD than nonsevere BPD infants (p = 0.03). There were significant differences between infants with and without severe BPD in the duration of endotracheal ventilation (p = 0.00, odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01–1.06), the duration of supplemental oxygen (p = 0.00, OR, 1.02; 95% CI, 1.01–1.03) before 36 weeks of postmenstrual age, and the frequency of sepsis after 7 postnatal days (p = 0.01, OR, 1.73; 95% CI, 1.18–2.54). Conclusion Cs are more likely to be present in the severe BPD infants with longer duration of endotracheal ventilation.

Background: The aim of this retrospective study was to evaluate the influence of prenatal diagnosis on perinatal outcomes of congenital heart disease (CHD) over a 17 year period at a single center. Methods: The perinatal outcome of CHD in 146 patients diagnosed on fetal echocardiography between 1994 and 2010 were reviewed. The characteristics of 193 neonatal inpatients with CHD treated at the authors’ department between 2001 and 2010 were also analyzed; among the inpatients, 61 were diagnosed before birth (prenatal group) and 132 were diagnosed after birth (postnatal group). Results: Among the 146 patients prenatally diagnosed with CHD, the prenatal mortality, including abortion and stillbirth, decreased from 1994 to 2010. Among the 193 neonatal inpatients, the prenatal group had lower gestational age and bodyweight than the postnatal group. Further, the prenatal group had lower blood pH at admission, but no patient in that group experienced ductal shock, although six patients in the postnatal group did. The average dose of prostaglandin E1 used in duct-dependent CHD was significantly lower in the prenatal group than in the postnatal group (3.4 vs. 4.6 ng/kg per min; P = 0.015). Conclusions: Prenatal diagnosis of CHD enables planned labor, prevents ductal shock, and reduces prostaglandin E1 side-effects and medical expenditure.

Aims: Hypoxia is known to influence cardiovascular (CV) function, in part, through adenosine receptor activation. We have shown in a mouse model that during primary cardiac morphogenesis, acute maternal hypoxia negatively affects fetal heart rate, and recurrent maternal caffeine exposure reduces fetal cardiac output (CO) and downregulates fetal adenosine A2A receptor gene expression. In the present study, we investigated whether maternal caffeine dosing exacerbates the fetal CV response to acute maternal hypoxia during the primary morphogenesis period. Material and Methods: Gestational-day-11.5 pregnant mice were exposed to hypoxia (45 s duration followed by 10 min of recovery and repeated 3 times) while simultaneously monitoring maternal and fetal CO using high-resolution echocardiography. Results: Following maternal hypoxia exposure, maternal CO transiently decreased and then returned to pre-hypoxia baseline values. In contrast to a uniform maternal cardiac response to each exposure to hypoxia, the fetal CO recovery time to the baseline decreased, and CO rebounded above baseline following the second and third episodes of maternal hypoxia. Maternal caffeine treatment inhibited the fetal CO recovery to maternal hypoxia by lengthening the time to CO recovery and eliminating the CO rebound post-recovery. Selective treatment with an adenosine A2A receptor antagonist, but not an adenosine A1 receptor antagonist, reproduced the altered fetal CO response to maternal hypoxia created by caffeine exposure. Conclusions: Results suggest an additive negative effect of maternal caffeine on the fetal CV response to acute maternal hypoxia, potentially mediated via adenosine A2A receptor inhibition during primary cardiovascular morphogenesis.

Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs.

Objectives : To evaluate whether peripheral arterial catheter management is more effective than umbilical arterial management in very preterm neonates. Methods : Thirty-eight very preterm neonates born in Fukushima Medical University Hospital between October 2008 and March 2010 were evaluated. A peripheral arterial catheter was inserted in 19 neonates (peripheral group) and an umbilical arterial catheter in the remaining 19 neonates (umbilical group). Results : The median gestational ages of the peripheral and umbilical groups were 195 and 185 days, respectively (p=0.04). The systolic and diastolic blood pressure (BP) was significantly higher in the peripheral group than in the umbilical group (p=0.03 and p=0.001). There was a significant relationship between BP at cannulation and urinary output after cannulation for 24 h in the peripheral group (rs=0.49, p=0.03) ; however, no such significant relationship was found in the umbilical group. Conclusions : We considered that peripheral artery catheters provide a well-functioning route for continuous BP monitoring, even in very preterm neonates. Because umbilical catheter placement might affect urinary output, we speculated that peripheral arterial catheter placement would be a more effective management strategy than umbilical arterial catheter placement in very preterm neonates. Further studies of larger populations are necessary to evaluate the effectiveness of arterial management including long-term follow-up studies.

Isolated levocardia (IL) is a rare type of situs inversus in which the heart is in the normal left-side position, but the abdominal viscera are in the dextroposition. Polysplenia is a congenital disorder affecting the asymmetric organs, including the heart, lungs, bronchi, liver, stomach, intestines, and spleen. In this report, we present a rare type satisfying the characteristics of both IL and polysplenia, confirmed by several imaging investigations, which revealed normally structured lungs and heart and the existence of the inferior vena cava (IVC), which runs on the left side, returns to the anterior-right side at the liver, and returns to the right atrium directly. Anatomical investigation and careful observation will make it possible to improve the prognosis of IL.

Barth syndrome is an X-linked disorder usually diagnosed in infancy. It is characterized by hypotonia, dilated cardiomyopathy, neutropenia, growth retardation, and 3-methylglutaconic aciduria. The syndrome is typically caused by mutations in the TAZ (G4.5) gene, which encodes a novel protein family called the tafazzins. We report the case of two brothers with Barth syndrome and left ventricular noncompaction (LVNC) caused by a splice donor mutation in TAZ. Both had impaired sucking ability at the age of 2 months. The elder brother was diagnosed with LVNC at the age of 4 months; by that time he had developed severe heart failure with metabolic decompensation. He died at 12 months of age due to intractable heart failure despite pharmacological therapy with diuretics, an angiotensin-converting enzyme inhibitor, and a beta-blocker. However, the younger brother, who was diagnosed as having Barth syndrome and LVNC with heart failure at the age of 2 months, received early medical treatment and demonstrated normal echocardiographic findings. Conclusion: The clinical courses of Barth syndrome observed in our cases show the phonotypic variability of this syndrome and suggest that early therapy may be beneficial for maintaining cardiac function.

To examine the expression levels of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMCs) and serum cortisol levels in cord blood from term infants.The study population consisted of 172 term infants who were delivered from healthy pregnant women. GRalpha and GRbeta expression levels, and serum cortisol level in cord blood were determined by real-time PCR and ELISA, respectively.Detection rates of GRalpha, GRbeta, and GAPDH were 100%, 63.4%, and 100%, respectively. The expression level of GRalpha was about 200 times that of GRbeta. There were no associations between GR expression level and clinical variables. There were significant associations of low UmApH, maternal gravidity or parity, and vaginal delivery with a high cortisol level; however, there were no correlations between GR expression levels and cortisol level.It is considered that glucocorticoid effects could be expected from the fetal period to the neonatal period, because GRalpha expression level was not related to perinatal factors, GRbeta expression level, and cortisol level in term infants. Further studies of larger populations including very preterm and small for gestational age infants are necessary to determine the balance of expression between GRalpha and GRbeta, and cortisol level.

Hyperammonemia of newborns should be treated promptly, and the outcome depends on the rapid elimination of excessive plasma ammonia. We encountered a case of transient hyperammonemia in an extremely low-birthweight infant whose plasma ammonia decreased sufficiently after continuous hemodialysis therapy. It seems that continuous hemodialysis therapy using the peripheral artery and umbilical vein is useful for hyperammonemia of extremely low-birthweight infants; however, there are several problems to consider due to the immaturity of these infants.

Routine surveillance in a neonatal intensive care unit (NICU) showed an increased detection of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-E. coli) in August 2012, following nearly a year without detection.To describe the investigation and interventions by a hospital infection control team of an outbreak of ESBL-E. coli in a NICU.Six neonates with positive cultures of ESBL-E. coli (five with respiratory colonization, one with a urinary tract infection), control infants who were negative for ESBL-E. coli during the study period, and mothers who donated their breast milk were included. A case-control study was performed to identify possible risk factors for positive ESBL-E. coli cultures and molecular typing of isolated strains by pulsed-field gel electrophoresis.The odds ratio for ESBL-E. coli infection after receiving shared unpasteurized breast milk during the study period was 49.17 (95% confidence interval: 6.02-354.68; P0.05). The pulsed-field gel electrophoresis pattern showed that all strains were identical, and the same pathogen was detected in freshly expressed milk of a particular donor. After ceasing the breast milk sharing, the outbreak was successfully terminated.This outbreak indicates that contamination of milk packs can result in transmission of a drug-resistant pathogen to newborn infants. Providers of human breast milk need to be aware of the necessity for low-temperature pasteurization and bacterial cultures, which should be conducted before and after freezing, before prescribing to infants.

A 9-year-old girl developed influenza A H1N1 pdm09-associated myocarditis and pericarditis 2 days after starting zanamivir therapy. The virus was detected in the respiratory tract but not in the serum or pericardial effusion. The virus sampled from the respiratory tract had normal susceptibility to neuraminidase inhibitors. Although no differences in interferon-γ, interleukin (IL)-1β, and tumor necrosis factor-α were observed between the plasma and pericardial effusion, some inflammatory cytokines or chemokines (IL-6 and IL-8) and vascular endothelial growth factor were remarkably elevated in the pericardial effusion compared with the plasma. This suggested that the influenza virus, after infecting the respiratory tract, affected the myocardium, causing myocarditis to gradually develop, which might have been followed by an autoreactive pericarditis causing increased pericardial effusion. Therefore, influenza-associated myocarditis should be considered when influenza patients have respiratory and cardiac involvement, even during treatment with a neuraminidase inhibitor.

Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists.

The incidence of measles epidemics has decreased recently owing to the development and widespread use of measles vaccine in the United States of America and Europe. However, repeated measles epidemics have been reported in Japan. Here, the authors report a case of an extremely low body weight infant (ELBWI) whose mother had a measles virus infection. Real-time PCR was performed on the infant's blood and urine samples and skin, nasal secretion, and anal swabs, as well as on the mother's breast milk, blood samples and throat swabs. The infant was found to be positive for measles virus by PCR, but not immunoglobulin M positive. An earlier report showed that there were no such cases in which the patient was found to be positive for measles virus by real-time PCR but was not infected by the measles virus.

The hemodynamic effects of olprinone, a newly synthesized phosphodiesterase (PDE) III inhibitor, were assessed in patients with a large cardiac left-to-right shunt. Ten patients with a large ventricular septal defect (VSD) were evaluated during cardiac catheterization. Olprinone was administered as a bolus, 20 microg/kg body weight, and hemodynamic data were obtained before and after the administration. Heart rate and systemic flow increased significantly after administration. On the other hand, olprinone significantly reduced left and right atrial pressure, the systolic pulmonary/arterial pressure ratio, and systemic vascular resistance. However, pulmonary flow and pulmonary vascular resistance were not changed. These results suggested that olprinone had a positive inotropic effect and selective vasodilator effect on patients with a large ventricular left-to-right shunt. Thus, PDE inhibitors may be beneficial for the treatment of patients with a large VSD.

This study was designed to determine, first, the stiffness of the pulmonary arteries and, second, the relationship between the stiffness of the pulmonary arteries and the success rate of balloon angioplasty in patients with complete transposition after an arterial switch operation. Indexes of pulmonary arterial wall stiffness, percent change in the radius during a cardiac cycle and the pressure elastic modulus, were calculated from the pulmonary arterial pressure and radius measured from a cineangiogram. Of the patients, 13 had no significant stenosis, while 25 had significant stenoses and, therefore, underwent balloon angioplasty. In all, we dilated 33 stenotic lesions. In the presence or absence of postoperative pulmonary stenosis, the percent change in the radius of the pulmonary trunk was significantly less than the normal value. The pressure elastic modulus of the trunk and its branches was significantly greater than normal, and increased significantly with time after the operation. In patients without pulmonary stenosis, the systolic pulmonary arterial pressure increased concomitantly with the pressure elastic modulus. Balloon dilation was successful at 17 locations and unsuccessful at 16 locations. The percent change in radius was significantly less for the failures than for the successes. Prior to 3.5 years after the operation, the pressure elastic modulus was < 400 g/cm2at most locations and balloon dilation was successful in 88%. More than 3.5 years after the operation, the pressure elastic modulus was < 400 g/cm2in 11 of 15 locations, and balloon dilation was successful in only one location. The increased stiffness of the pulmonary artery may result in increased pulmonary systolic pressure in patients without pulmonary stenosis, and result in a low success rate for balloon angioplasty in patients with pulmonary stenosis.

Caffeine is widely ingested in various beverages and foods such as coffee, tea, soft drinks, chocolate, and certain medications. Caffeine crosses the placenta and brain–blood barriers, and its half-life is prolonged during pregnancy. Studies have shown that caffeine affects perinatal cardiovascular (CV) function, increases the risk of spontaneous abortion, and intrauterine growth restriction (IUGR). We have studied the effects of maternal caffeine exposure on fetal CV function and growth using a mouse animal model, and found that maternal caffeine exposure transiently depresses fetal CV function during the primary morphogenesis period and recurrent maternal caffeine exposure induces IUGR during later development. The effect of caffeine on the developing fetus appears to be mediated by caffeine inhibition of adenosine A2A receptor. In this chapter, we discuss the adverse effect of maternal caffeine exposure on developing fetal CV function and adenosine receptor.

Background Although glucocorticoid hormones play important roles in fetal development, the expression of their receptors in the whole blood of preterm infants remains unknown. Objectives The aim of this study was to investigate the levels of glucocorticoid receptor (GR) α and β in the whole blood of preterm and term infants. Study design The study group consisted of 131 infants, of which 54 (41%) were preterm. Whole blood from preterm and term infants was analyzed by real-time PCR to monitor the levels of each receptor mRNA. Results GRβ mRNA were detected in 96.6% and GRα mRNA in 100% of participants. The GRα and GRβ isoforms were detected at a ratio of 1:0.0002. GRβ mRNA/GAPDH expression in preterm infants was significantly higher than that in term infants (p=0.002). There was significant correlation between GRα/GRβ ratio and birth weight in preterm infants (rs=0.317, p=0.019), as well as between GRβ/GAPDH expression and birth weight (rs=-0.296, p=0.030). Furthermore, in preterm infants, GRβ/GAPDH expression was higher in those with SGA than in those without SGA (p=0.022). Conclusion Importantly, in preterm infants, both the expression of GRβ and the GRα/GRβ ratio were associated with birth weight. Further studies with larger populations are necessary to determine the relation between the expression of GR and the clinical relevance of preterm infants.