記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The standard of care in Japan for preterm very low-birth-weight (VLBW) infants has long been at the highest level internationally, owing to advances in technology and the perinatal medical system throughout the country. METHODS: To identify issues for further improvement of outcomes for preterm VLBW infants in our neonatal intensive care unit (NICU), perinatal care practice was reviewed by analyzing data from medical records on pregnancy complications and management and infant mortality and morbidity. RESULTS: Data from 250 preterm VLBW infants, excluding those with severe congenital anomalies, were analyzed. There were 49 cases (19.6%) of cumulative morbidity, including infants who died before discharge and those who had major complications such as bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, and retinopathy of prematurity. The prevalence remained constant throughout the study period. Infants born via medically indicated preterm birth had a higher cumulative morbidity rate than those born via spontaneous preterm birth. Small-for-gestational-age status was the only factor significantly associated with cumulative morbidity in multivariate analysis. Of all the infants, 69 (47.3%) completed a course of antenatal corticosteroids (ACS). CONCLUSIONS: The quality of neonatal intensive care for preterm VLBW infants in our NICU was consistent with outcomes for top-ranked NICUs in Japan. Critical issues in improving outcomes for these infants include determining the optimal timing of delivery by comprehensively assessing fetal well-being and promoting ACS.

DOI： 10.1272/jnms.JNMS.2025_92-307

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Drug resistance is a serious problem in leukemia therapy. A novel purine nucleoside analogue, nelarabine, is available for the treatment of children with T cell acute lymphoblastic leukemia. We investigated the mechanisms of drug resistance to nelarabine. METHODS: Nelarabine-resistant cells were selected by stepwise and continuous exposure to nelarabine using the limiting dilution method in human B and T cell lymphoblastic leukemia cell lines. Expression analysis was performed using real-time polymerase chain reaction, and epigenetic analysis was performed using methylation-specific polymerase chain reaction and chromatin immunoprecipitation. RESULTS: The RNA expression level for deoxycytidine kinase (dCK) was decreased in nelarabine-resistant leukemia cells. There were no differences between the parental and nelarabine-resistant leukemia cells in the methylation status of the promoter region of the dCK gene. In the chromatin immune precipitation assay, decreased acetylation of histones H3 and H4 bound to the dCK promoter was seen in the nelarabine-resistant cells when compared to the parental cells. Furthermore, treatment with a novel histone deacetylase inhibitor, vorinostat, promoted the cytotoxic effect of nelarabine along with increased expression of the dCK gene, and it increased acetylation of both histones H3 and H4 bound to the dCK promoter in nelarabine-resistant leukemia cells. The combination index showed that the effect of nelarabine and vorinostat was synergistic. CONCLUSION: This study reports that nelarabine with vorinostat can promote cytotoxicity in nelarabine-resistant leukemia cells through epigenetic mechanisms.

DOI： 10.1007/s00280-021-04373-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kawasaki disease (KD) is a systemic vasculitis of unknown cause and is associated with various digestive disorders, although only a few cases of intussusception associated with KD have been reported. We describe a case of intussusception followed by KD in a 3-year-old boy. The patient was admitted to our hospital for evaluation of severe abdominal pain. Because the target sign was seen on ultrasonography, intussusception was diagnosed and hydrostatic reduction was performed. On the second day after admission, he developed a high fever (38°C) and an irregular rash over his whole body. On the fourth day after admission, the high fever continued, and bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, strawberry tongue, indurated edema of the dorsa of the hands and feet, and diffuse erythema of the palms and soles appeared, and KD was ultimately diagnosed. He was treated with intravenous immunoglobulin 2 g/kg, aspirin 30 mg/kg/day, and prednisolone 2 mg/kg/day. The high fever and other clinical symptoms resolved immediately after the start of treatment. There was no relapse of KD symptoms after initial treatment, and periungual desquamation was observed on the 10th day after admission. He was discharged on the 15th day, without abnormalities such as coronary dilatation, 3 months after the onset of KD symptoms. Patients with intussusception and KD were older (≥3 years vs <3 years) than those with intussusception alone. In addition, the site of intussusception in KD was mainly colonic rather than ileocolic. If intussusception precedes development of the characteristic clinical symptoms of KD, diagnosis of KD may be delayed. KD should be considered in children older than 3 years with intussusception at a colonic site.

DOI： 10.1272/jnms.JNMS.2020_87-606

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In Japan, pneumococcal vaccine has been routinely administered since 2010 to prevent invasive pneumococcal diseases such as Streptococcus pneumoniae meningitis. We describe a case of pneumococcal meningitis in a 7-month-old girl who had received three doses of 13-valent pneumococcal conjugate vaccine. Brain magnetic resonance imaging showed infarcts in the right frontal region, and she was treated with antibiotics, intravenous immunoglobulin, dexamethasone, and edaravone. On day 27, an enhanced brain CT scan showed improvement of abnormal findings in the frontal region, except for slight atrophy. The S. pneumoniae serotype was 12F, which is not included in the 13-valent pneumococcal conjugate vaccine. A future vaccine is expected to use cross-reactivity to target common antigens.

DOI： 10.1272/jnms.JNMS.2020_87-510

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