掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society for Pediatric Endocrinology  

DOI： 10.1297/cpe.2024-0079

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Psychosocial stress can induce various physical symptoms, including fever, which is a commonly seen symptom in pediatric practice. In cases of unexplained fever, psychogenic fever should be considered as a potential cause. Children with neurodevelopmental disorders may be more vulnerable to stress and therefore more prone to developing somatic symptoms than their peers. This study aimed to elucidate the characteristics of children with psychogenic fever and comorbidity. METHODS: This study included 21 patients with psychogenic fever who visited the Department of Pediatric Psychosomatic Medicine, Okayama University Hospital. Information on age, sex, disease onset, final estimated diagnosis, comorbidities, treatment course, and outcome was obtained from the patients' medical records. RESULTS: Of the 21 patients included, 7 were boys and 14 were girls, and their median age was 13.0 (range: 8.6-14.6) years. A total of 19 patients had no attendance at school, and all patients showed signs of maladjustment in school. The comorbidities included orthostatic dysregulation (n = 4) and migraine (n = 3). Neurodevelopmental disorders were observed in nine patients, eight of whom were diagnosed after the initial visit. The mean treatment duration was 37.2 months. The outcomes were complete remission (n = 9), improvement (n = 4), discontinuation (n = 1), and referral to another physician (n = 7). CONCLUSION: Various comorbidities were observed in the patients of this study with psychogenic fever, including the coexistence of neurodevelopmental disorders, such as autistic spectrum disorder. Children with neurodevelopmental disorders are prone to psychological stress resulting from difficulties in social adjustment. It is crucial to understand the developmental characteristics and environmental adaptation of patients to facilitate accurate diagnosis and treatment.

DOI： 10.1186/s13030-024-00322-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Introduction

Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by bone fragility. Bisphosphonates (BISs) have become the mainstream treatment in children with OI. However, an optimal treatment protocol has not yet been established, while BIS treatment tends to be administered to normalize bone mineral density (BMD). Bone quality is an important component of bone strength. The trabecular bone score (TBS) is a quantitative measure of the microstructure that affects bone quality. This study investigated the TBS during BIS treatment in children with OI.

Materials and methods

Twenty-nine children with OI were enrolled and classified into two groups: mild (type 1) and moderate to severe (types 3 and 4). Dual-energy x-ray absorptiometry images were retrospectively analyzed for TBS calculation. The relationship between the areal BMD (aBMD), its Z-score, height-adjusted BMD (BMD_HAZ) Z-score, TBS, and TBS Z-score with the treatment duration was assessed for each group.

Results

In the mild group, the aBMD, its Z-score, and BMDHAZ Z-score showed a significant positive correlation with treatment duration (r = 0.68, 0.68, 0.72, respectively, p < 0.01). The TBS Z-score tended to increase with treatment duration, albeit without reaching significance. In the moderate to severe group, the TBS Z-score showed a significant positive correlation with treatment duration (r = 0.48, p < 0.01), in contrast to the aBMD Z-score, which did not increase. Finally, the BMDHAZ Z-score only showed a weak positive correlation with treatment duration (r = 0.37, p < 0.01).

Conclusion

Because BIS affect the BMD and TBS differently based on the severity of OI, treatment goals may need to be stratified by disease severity.

DOI： 10.3389/fped.2024.1500023

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pediatric ALK-positive anaplastic large cell lymphoma is a rare subtype of non-Hodgkin lymphoma, and approximately 30% of patients relapse following treatment with conventional chemotherapy. Alectinib monotherapy has demonstrated excellent activity in relapsed and refractory ALCL, but its role as a maintenance therapy after hematopoietic cell transplantation is unclear. We experienced a relapse case of pediatric ALK-positive ALCL with central nervous system involvement treated with alectinib maintenance therapy following cord blood transplantation. The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.

DOI： 10.1007/s00277-024-06000-7

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記述言語：日本語   出版者・発行元：(一社)日本小児感染症学会  

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記述言語：英語  

DOI： 10.1186/s13030-024-00319-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A decreased glomerular filtration rate (GFR), estimated using creatinine (Cr- eGFR), is often found at the initial presentation of anorexia nervosa (AN). Its pathophysiology has been explained mainly by dehydration, and chronic hypokalemia is also thought to be a cause. However, because we have often experienced cases of AN with decreased Cr-eGFR without these conditions, we must consider different etiologies. The focus of this paper is on low free triiodothyronine (FT3) syndrome. We also discuss the utility of eGFR, estimated using cystatin-C (CysC-eGFR), for these patients. METHODS: The data of 39 patients diagnosed with AN between January 2005 and December 2023 was available for study. The characteristics of patients at the lowest and highest body mass index standard deviation score (BMI-SDS) were examined. Data on the parameters Cr-eGFR, CysC-eGFR, dehydration markers, potassium (K), and hormonal data and BMI-SDS were assessed during the treatment course to evaluate the correlations in these parameters. Blood hematocrit, uric acid (UA), blood urine nitrogen (BUN) level, and urine specific gravity were adopted as dehydration markers; FT3, free thyroxine, thyroid stimulating hormone, and insulin-like growth factor were adopted as hormonal data. Cr-eGFR and simultaneously evaluated dehydration markers, K, or hormonal data were extracted and correlations associated with the changes in BMI-SDS were examined. Furthermore, Cr-eGFR and simultaneously assessed CysC-eGFR were compared. RESULTS: When the BMI-SDS was at the lowest value, low-FT3 syndrome was shown. Severe hypokalemia was not found in our study. A linear relation was not found between Cr-eGFR and BMI-SDS. A statistically significant correlation was found between Cr-eGFR and FT3 (p = 0.0025). Among the dehydration markers, statistically significant correlations were found between Cr-eGFR and BUN or UA. The difference between Cr-eGFR and CysC-eGFR was prominent, and CysC-eGFR showed much higher values. CONCLUSIONS: Our data indicates that low-FT3 syndrome and dehydration were related to the renal function of our patients with AN. Furthermore, our data suggest that caution is needed in the interpretation of kidney function evaluation when using CysC-eGFR in cases of AN.

DOI： 10.1186/s13030-024-00316-6

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

13番染色体長腕部分トリソミー(以下,13q部分トリソミー)に全前脳胞症(holoprosencephaly:HPE)が合併した1例を経験した.小頭,眼間狭小,鼻中隔欠損,右唇顎口蓋裂など顔面正中部の低形成を認め,頭部単純MRI検査でlobar型のHPEと診断した.生後3ヵ月でWest症候群を発症し,急性呼吸不全のため4歳2ヵ月で死亡した.染色体核型は46,XX,rec(13)dup(13q)inv(13)(p12q14.1)matで,母の腕間逆位に由来していた.13q部分トリソミーの表現型は,13トリソミーに比べ軽症例が多く,生命予後も良好と考えられてきた.本症例は,これまでの報告例には共通しない表現型としてHPEを合併したために重篤な経過を示した.13q部分トリソミーの表現型と重複部位の関連を明らかにするためには,さらなる症例の集積が必要と考えられる.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J04116&link_issn=&doc_id=20240913470018&doc_link_id=10.34456%2Fjjspnm.60.2_287&url=https%3A%2F%2Fdoi.org%2F10.34456%2Fjjspnm.60.2_287&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

DOI： 10.3390/ijms25158370

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Controlling pulmonary blood flow in patients who have undergone Norwood palliation, especially early postoperatively, is challenging due to a change in the balance of systemic and pulmonary vascular resistance. We applied a combination therapy of clipping and balloon angioplasty for right ventricle-pulmonary artery (RV-PA) shunt to control pulmonary blood flow, but the influence of the combination therapy on the PA condition is uncertain. Retrospectively analysis was conducted of all infants with hypoplastic left heart syndrome who had undergone Norwood palliation with RV-PA shunt at Okayama University Hospital from January 2008 to September 2022. A total of 50 consecutive patients underwent Norwood palliation with RV-PA shunt in this study period. Of them, 29 patients underwent RV-PA shunt flow clipping, and the remaining 21 had unclipped RV-PA shunt. Twenty-three patients underwent balloon angioplasty for RV-PA shunt with clips. After balloon angioplasty, oxygen saturation significantly increased from 69 (59-76)% to 80 (72-86)% (p < 0.001), and the narrowest portion of the clipped conduit significantly improved from 2.8 (1.8-3.4) to 3.8 (2.9-4.6) mm (p < 0.001). In cardiac catheterizations prior to Bidirectional cavo-pulmonary shunt (BCPS), there were no significant differences in pulmonary-to-systemic flow ratio (Qp/Qs), ventricular end-diastolic pressure, Nakata index, arterial saturation, mean pulmonary artery pressure and pulmonary vascular resistance index. On the other hand, in Cardiac catheterizations prior to Fontan, Nakata index was larger in the clipped group (p = 0.02). There was no statistically significant difference in the 5-year survival between the two groups (clipped group 96%, unclipped group 74%, log-rank test: p = 0.13). At least, our combination therapy of clipping and balloon angioplasty for RV-PA shunt did not negatively impact PA growth. Although there is a trend toward better but not statistically significant difference in outcomes in the clipped group compared to the non-clipped group, this treatment strategy may play an important role in improving outcomes in hypoplastic left heart syndrome.

DOI： 10.1007/s00246-024-03579-6

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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担当区分：最終著者   記述言語：日本語   出版者・発行元：日本小児心身医学会-中国四国地方会  

関係機関につながりにくい不登校男児に小児科医,公認心理師(CP)が行った面接の過程を振り返り報告する.初診時小5男児(A)は,不登校を主訴として来院した.Aは数ヶ所の医療機関で自閉スペクトラム症(ASD),境界知能と診断された.小学校1年生から不登校があり,小児科,児童精神科,フリースクールなどと関わりがあったが通院や通所は長続きしなかった.当初Aは妄想的な自己肥大的発言や被害的発言が多く,幻聴や幻覚が懸念された.そのため,感情に焦点を当てて洞察を深める心理面接は侵襲的と考えて,CPは今,出来ている事を聞くことに徹した.コロナ禍等で半年間受診が途絶えた時期もあったが,通院は継続できた.学校との関わりを持つことで,困難であった放課後登校が継続可能となり,現実的な心配事を相談する経験を経て通信制高校へ進学した.専門機関とつながりにくい親子が小児科の非侵襲的な関わりで関係維持が可能となった.学校での関わりが成長を促した.(著者抄録)

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記述言語：日本語   出版者・発行元：日本小児心身医学会-中国四国地方会  

関係機関につながりにくい不登校男児に小児科医,公認心理師(CP)が行った面接の過程を振り返り報告する.初診時小5男児(A)は,不登校を主訴として来院した.Aは数ヶ所の医療機関で自閉スペクトラム症(ASD),境界知能と診断された.小学校1年生から不登校があり,小児科,児童精神科,フリースクールなどと関わりがあったが通院や通所は長続きしなかった.当初Aは妄想的な自己肥大的発言や被害的発言が多く,幻聴や幻覚が懸念された.そのため,感情に焦点を当てて洞察を深める心理面接は侵襲的と考えて,CPは今,出来ている事を聞くことに徹した.コロナ禍等で半年間受診が途絶えた時期もあったが,通院は継続できた.学校との関わりを持つことで,困難であった放課後登校が継続可能となり,現実的な心配事を相談する経験を経て通信制高校へ進学した.専門機関とつながりにくい親子が小児科の非侵襲的な関わりで関係維持が可能となった.学校での関わりが成長を促した.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. METHODS: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. RESULTS: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 μmol/L, 51.2 ± 23.7 μmol/L, 42.4 ± 15.2 μmol/L, and 33.8 ± 9.4 μmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/μL, 613 ± 625/μL, 466 ± 375/μL, and 292 ± 228/μL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. CONCLUSION: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age.

DOI： 10.1016/j.pedneo.2023.08.006

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Objective

This study primarily focused on the diagnostic interval (DI), defined as the duration from the onset of leukemic symptoms to diagnosis. We investigated whether a prolonged DI is associated with the outcomes of pediatric leukemia.

Methods

We retrospectively collected data of children with newly diagnosed pediatric leukemia at Okayama University Hospital from January 2007 to December 2022. Survival analyses were conducted using Kaplan–Meier methods, and an unadjusted analysis to compare differences in survival was performed using the log‐rank test.

Results

In total, 103 children with leukemia were included in the analysis. The median DI was 20 days (interquartile range, 9.5–33.5 days). A prolonged DI (≥30 days) demonstrated no association with either 5‐year event‐free survival (70.1% for &lt;30 days and 68.3% for ≥30 days, p = .99, log‐rank test) or overall survival (84.7% for &lt;30 days and 89.4% for ≥30 days, p = .85, log‐rank test).

Conclusions

A prolonged DI was not associated with the survival of children with leukemia. If a precise classification of leukemia biology is provided for pediatric patients, a prolonged DI may have little impact on the prognosis of these patients.

DOI： 10.1111/ejh.14162

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.

DOI： 10.1002/ajmg.a.63525

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: This study aimed to develop models for predicting total serum bilirubin by correcting errors of transcutaneous bilirubin using machine learning based on neonatal biomarkers that could affect spectrophotometric measurements of tissue bilirubin. METHODS: This retrospective study included infants born at our hospital (≥36 weeks old, ≥2,000 g) between January 2020 and December 2022. Infants without a phototherapy history were included. Robust linear regression, gradient boosting tree, and neural networks were used for machine learning models. A neural network, inspired by the structure of the human brain, was designed comprising three layers: input, intermediate, and output. RESULTS: Totally, 683 infants were included. The mean (minimum-maximum) gestational age, birth weight, participant age, total serum bilirubin, and transcutaneous bilirubin were 39.0 (36.0-42.0) weeks, 3,004 (2,004-4,484) g, 2.8 (1-6) days of age, 8.50 (2.67-18.12) mg/dL, and 7.8 (1.1-18.1) mg/dL, respectively. The neural network model had a root mean square error of 1.03 mg/dL and a mean absolute error of 0.80 mg/dL in cross-validation data. These values were 0.37 mg/dL and 0.28 mg/dL, smaller compared to transcutaneous bilirubin, respectively. The 95% limit of agreement between the neural network estimation and total serum bilirubin was -2.01 to 2.01 mg/dL. Unnecessary blood draws could be reduced by up to 78%. CONCLUSION: Using machine learning with transcutaneous bilirubin, total serum bilirubin estimation error was reduced by 25%. This integration could increase accuracy, lessen infant discomfort, and simplify procedures, offering a smart alternative to blood draws by accurately estimating phototherapy thresholds.

DOI： 10.1159/000535970

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6-8, 9-11, and 12-14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%-4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%-4.0%) and 9- to 11-year (0.9%-2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%-8.9%) and girls of many age groups (2.6%-8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary.

DOI： 10.1111/cob.12636

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To examine associations between children being born small for gestational age and childhood hospitalisation following term and preterm births. METHODS: This study included 34 564 children from a nationwide population-based longitudinal survey starting in 2010, comprising 32 603 term births and 1961 preterm births. Children's hospitalisation history was examined during two observational periods, 6-18 and 6-66 months of age. Logistic regression analysis was conducted, adjusting for child and parental confounders, with children born appropriate for gestational age as reference. RESULTS: Children born small for gestational age were more likely to be hospitalised during early childhood than those born appropriate for gestational age. The odds ratio (95% confidence interval) for hospitalisation from 6 to 66 months of age was 1.19 (1.05-1.34) in term children born small for gestational age and 1.47 (1.05-2.06) for preterm children born small for gestational age, compared with those born appropriate for gestational age. The risk of hospitalisation from 6 to 66 months of age in children born small for gestational age was observed for bronchitis/pneumonia. CONCLUSION: We observed the adverse effects of small for gestational age on hospitalisation during early childhood in both term and preterm births, particularly for bronchitis and pneumonia.

DOI： 10.1111/apa.17032

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

DOI： 10.1186/s13223-023-00859-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate the incidence and risk factors of small-for-gestational age (SGA) short stature at 2 and 3 years of age in SGA offspring born to women with hypertensive disorders of pregnancy (HDP). METHODS: We examined 226 women with HDP whose respective SGA offspring were delivered. RESULTS: Eighty offspring (41.2%) were diagnosed with SGA short stature. The prematurity before 32 weeks of gestation was the most significant factor for catch-up growth failure. CONCLUSION: In SGA offspring born to women with HDP, SGA short stature incidence was high, and the risk factor was prematurity before 32 weeks of gestation.

DOI： 10.1080/10641955.2023.2187623

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children.

DOI： 10.3390/ijms242015450

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担当区分：最終著者   記述言語：日本語   出版者・発行元：一般社団法人 日本輸血・細胞治療学会  

小児がん患者における輸血後鉄過剰症については，海外からは報告が散見される．成人と同様，白血病等における同種造血細胞移植患者において，移植前の血清フェリチン値と合併症の相関等が議論されているが，日本国内からはまだまとまった報告はない．我々は，肝障害を来し，輸血後鉄過剰症と肝移植片対宿主病（GVHD）との鑑別に磁気共鳴画像（MRI）が有用であった2例を経験した．2例とも急性骨髄性白血病であり，肝GVHDとして免疫抑制療法等を行ったにもかかわらず遷延する肝障害を呈していた．高フェリチン血症を認めたためMRI撮像したところ，高度鉄沈着を示唆する所見を呈した．輸血後鉄過剰症として鉄キレート療法を行って肝障害が改善した．小児がん患者において，骨髄抑制期間が長く頻回の輸血を要するような症例では，急性期に臓器障害を伴う輸血後鉄過剰症を示す可能性があるが，治療介入の指針や時期については明らかになっていない．今後日本国内でも大規模な調査が必要と思われる．

DOI： 10.3925/jjtc.69.605

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Children with a congenital heart disease (CHD) are at a higher risk of developing epilepsy than the general population, but detailed characteristics of CHD-associated epilepsy have not been clarified. The purposes of this study were to determine the risk factors for developing epilepsy associated with CHD and to elucidate the characteristics of such epilepsy. METHODS: We performed a retrospective cohort study based on medical records of pediatric patients with CHD who were born between January 2006 and December 2016, underwent cardiac surgery at Okayama University Hospital, and were followed up until at least age three years. Multivariate logistic regression analysis was used to determine factors particularly associated with epilepsy occurrence. In patients who developed epilepsy, clinical data on seizure characteristics were further investigated. RESULTS: We collected data from 1024 patients, and 41 (4.0%) developed epilepsy. The presence of underlying disease (odds ratio [OR]: 2.413; 95% confidence interval [CI]: 1.150 to 4.883) and the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score category 2 (OR: 4.373; 95% CI: 1.090 to 29.150) and category 5 (OR: 10.385; 95% CI: 1.717 to 89.016) were significantly related to epilepsy occurrence. Of the 41 patients with epilepsy, 15 (including nine with hypoplastic left heart syndrome) had focal impaired awareness seizures specified as autonomic seizures with vomiting, which tends to escape detection. CONCLUSIONS: We clarified the risk factors for developing epilepsy in children with CHD. We also found that autonomic seizure with vomiting is an important symptom in these children.

DOI： 10.1016/j.pediatrneurol.2023.07.004

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記述言語：日本語   出版者・発行元：(公社)日本新生児成育医学会  

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記述言語：日本語   出版者・発行元：日本小児心身医学会-中国四国地方会  

子どもにとって,入院生活が心理発達面に与える影響は大きい.特に神経発達症児は,環境変化に適応しにくく,新規場面での不安や混乱から検査や治療に支障をきたすことがある.今回,入院中の神経発達症児へ適切な支援を行うため,現状を把握し課題を抽出することを目的に,岡山県内の小児病棟を有する7施設の医師,看護師を対象に質問紙調査を行った.その結果,回答者の97.6%が神経発達症児の入院を経験し,不適応行動に対して様々な対応や工夫を行っていた.一方で,医師の32.1%,看護師の65.3%は適切に対応するための知識不足を認識していた.また,医師・看護師以外の職種が生かされていない,情報共有が難しい,相談する場がないなど,多職種連携の課題が明らかになった.入院中の神経発達症児を支援するためには,神経発達症が専門でない小児科医や看護師が知識を習得し対応スキルの向上を図ること,保護者と情報共有して協力すること,多職種が協力して対応する支援体制の構築が必要だと考えられた.(著者抄録)

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記述言語：日本語   出版者・発行元：日本小児心身医学会-中国四国地方会  

子どもにとって,入院生活が心理発達面に与える影響は大きい.特に神経発達症児は,環境変化に適応しにくく,新規場面での不安や混乱から検査や治療に支障をきたすことがある.今回,入院中の神経発達症児へ適切な支援を行うため,現状を把握し課題を抽出することを目的に,岡山県内の小児病棟を有する7施設の医師,看護師を対象に質問紙調査を行った.その結果,回答者の97.6%が神経発達症児の入院を経験し,不適応行動に対して様々な対応や工夫を行っていた.一方で,医師の32.1%,看護師の65.3%は適切に対応するための知識不足を認識していた.また,医師・看護師以外の職種が生かされていない,情報共有が難しい,相談する場がないなど,多職種連携の課題が明らかになった.入院中の神経発達症児を支援するためには,神経発達症が専門でない小児科医や看護師が知識を習得し対応スキルの向上を図ること,保護者と情報共有して協力すること,多職種が協力して対応する支援体制の構築が必要だと考えられた.(著者抄録)

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担当区分：最終著者   記述言語：英語  

A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present.

DOI： 10.18926/AMO/65757

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. MATERIALS AND METHODS: We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005-2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. RESULTS: After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9-56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1-53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2-57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5-67.1]), antiviral use (65.7 % reduction [59.7-70.8]), and healthcare costs (49.1 % [95 %CI, 32.7-61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. CONCLUSIONS: Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices.

DOI： 10.1016/j.vaccine.2023.06.054

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記述言語：日本語   出版者・発行元：(NPO)日本小児循環器学会  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI. METHODS: A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9-15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression. RESULTS: Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 ± 13.5 vs. 67.9 ± 13.4, p < 0.001) and junior high schools (51.8 ± 14.6 vs. 61.3 ± 12.6, p < 0.001). This finding was observed in the physical, mental, self-esteem, friends, and school domains. Total QOL scores were significantly associated with school nonattendance (β =  - 3.2, 95% confidence interval [CI] =  - 5.8 to - 0.5, p = 0.022) and poor relationship with school (β =  - 5.0, 95% CI =  - 9.8 to - 0.4, p = 0.035). CONCLUSIONS: These results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI.

DOI： 10.1186/s13030-023-00278-1

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Involuntary exposure to tobacco smoke is suspected to be one of the risks factors that are associated with obesity in children. The purpose of this study was to examine the relationship between early childhood exposure to tobacco smoke and the risk of obesity and overweight in Japan. This study utilized a nationwide, population-based longitudinal survey. The participants were restricted to 32 081 children who had available information on maternal smoking history as well as childhood height and weight. We conducted a binomial log-linear regression analysis with children of non-smoking mothers as the reference group. The children with mothers who were smokers had a higher risk of developing obesity or being overweight compared to the children with mothers who were nonsmokers. The risk ratios were 1.20 (95% confidence interval [CI]: 1.09-1.32) for overweight and 1.17 (95% CI: 0.95-1.44) for obesity. Early exposure to maternal smoking increases the risk of being overweight and having obesity during childhood. The increased risk is more pronounced among children with mothers, smoked heavily, or parents, who were smokers.

DOI： 10.1111/cob.12572

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cob.12572

記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

予防接種後有害事象(AEFI)および予防接種ストレス関連反応(ISRR)に関連する動画講義視聴が小児科医の予防接種に対する知識、態度、自信、役割認識、自己効力感、行動に与える影響を調査した。介入前評価(pre study)に回答した日本小児科学会会員368名をA群とB群に分けてA群にのみオンラインでISRRに関する約20分間の動画講義を配布し、pre studyから約1ヵ月後にA群・B群に介入後評価(Post study)を行った。Post studyの回答者A群74名、B群95名を対象に動画講義視聴による介入効果について検討した。その結果、AEFIおよびISRRに関連する調査によってA群・B群の知識レベルが向上したが、予防接種に対する態度、自信、役割認識、自己効力感、実際の接種行動に与える影響は限定的であった。

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD. METHODS: This study was prospectively performed. Patients were divided into two groups and analyzed depending on whether KD symptoms improved by day 10 of illness. HRG, HMGB1, and other laboratory variables were measured before the first treatment in all cases and, in most cases, afterwards, for assessing trends. RESULTS: In this prospective study, we enrolled 60 patients with KD and 48 healthy controls. The HRG level in the KD group was significantly lower than that in the healthy control group; HMGB1 levels showed no obvious differences. In the KD group, HRG levels were negatively correlated with white blood cell and neutrophil counts. In the poor responders and responders groups, a tendency for a decrease in HRG and HMGB1 levels, respectively, was observed from pretreatment to post-treatment. CONCLUSIONS: HRG and HMGB1 are related to the pathogenesis of KD; low HRG and high HMGB1 levels cause resistance against KD treatment.

DOI： 10.1093/mr/roac040

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担当区分：最終著者   記述言語：英語  

Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.

DOI： 10.18926/AMO/65153

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Psychosomatic disorders are influenced by psychosocial factors such as interpersonal relationships. Coping behaviors, especially in frustrating situations, reflect a patient's ability to cope with stress, and it is important to assess these behaviors for the treatment of psychosomatic diseases. This study aimed to clarify the interpersonal relationships and coping behaviors of pediatric patients with psychosomatic diseases during frustrating situations simulated using the Rosenzweig Picture-Frustration study. This retrospective study included 126 patients (41 male, 85 female) with an average age of 12.9 (6-16) years who were consulted at the Department of Pediatric Psychosomatic Medicine at Okayama University Hospital from 2013 to 2018 and underwent the P-F study. Each score was compared with a standardization sample. The mean group conformity rating did not differ significantly between the participants and healthy children. Compared with healthy children, those with psychosomatic diseases were less likely to explain their perspective. The children with psychosomatic disorders responded to frustrating situations in a sensible and age-appropriate manner. However, they were less likely to respond by explaining their perspective to protect themselves.

DOI： 10.18926/AMO/65148

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. METHODS: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. RESULTS: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. CONCLUSIONS: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

DOI： 10.3389/fped.2023.1127053

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.JE20220265

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.

DOI： 10.3390/biomedicines11010212

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Neonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. While psychiatric drugs are a more common cause of NAS in Japan, infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate-induced NAS using variables available at birth. METHODS: In this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents. RESULTS: A total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z-score and Apgar score at 5 minutes < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C-statistics were 0.747 (95% CI: 0.638-0.856), and 0.795 (95% CI: 0.683-0.907), respectively, indicating good predictive accuracy of NAS onset for the models. CONCLUSIONS: This study developed models that predicted nonopiate-induced NAS with good accuracy, which may be further improved through the use of drug indices.

DOI： 10.1111/ped.15435

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担当区分：最終著者   記述言語：英語  

DOI： 10.1111/ped.15460

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Background

We sought to investigate the occurrence of adverse reactions in Japanese children aged 6 months to 4 years who received the BNT162b2 coronavirus disease 2019 (COVID‐19) vaccine, to examine parental considerations, and to evaluate potential risk factors associated with post‐vaccination fever.

Methods

This cross‐sectional survey study targeted 1617 children aged 6 months to 4 years who received their primary doses of BNT162b2 from November 10, 2022, to April 30, 2023, in Okayama Prefecture. We surveyed the occurrence of local and systemic reactions within 1 week after vaccination, and described the incidence proportions of adverse reactions for 515 participants overall and by age group. The study also examined the impact of previous COVID‐19 infection and co‐administration of the seasonal influenza vaccine on post‐vaccination fever. A survey also assessed parents' reasons for vaccinating their children and the sources of information they used.

Results

Adverse reactions were infrequent (5.2%, with fever ≥37.5°C; no cases exceeded 39°C) and did not increase with vaccine doses administered. The risk of post‐vaccination fever was not statistically associated with a history of COVID‐19—the adjusted risk ratio (aRR) was 0.99, and the 95% confidence interval (CI) was 0.41–2.39—but was associated with co‐administration of the seasonal influenza vaccine (aRR 3.24, 95% CI 1.14–9.18). Parental decisions regarding vaccination were influenced by official government guidelines and primary care physicians' opinion.

Conclusion

This study provides valuable insight into the safety profile of the BNT162b2 vaccine in Japanese children aged 6 months to 4 years. Further research involving larger cohorts and appropriate control groups is needed.

DOI： 10.1111/ped.15696

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan. METHODS: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence. RESULTS: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group. CONCLUSIONS: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare.

DOI： 10.3389/fped.2023.1127053

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. METHODS: This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or no-teprenone groups in a 1:1 ratio. We stratified patients by sex, age < and ≥ 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. RESULTS: One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). CONCLUSION: Teprenone afforded no clinical benefit. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs061200002 (registered on 20/May/2020).

DOI： 10.1371/journal.pone.0287501

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.

DOI： 10.1297/cpe.2023-0035

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本小児心身医学会  

小児の摂食障害では,明らかなやせ願望を呈さない回避・制限性食物摂取症の占める割合が,成人と比較して多いことが特徴である.今回われわれは,化学療法中に厳格な食事制限を行ったことを契機に摂食障害を来した男児例を経験した.急性白血病に対する化学療法の副作用のために著明な高脂血症が出現し,脂質制限食を開始したところ食事を摂らなくなった.ボディイメージの障害ややせ願望は認めなかった.厳しい食事制限が行われたことが大きな心理的ストレスとなり,食事は嫌なものという反応が形成され,条件付けが起こったと考え,回避・制限性食物摂取症と診断した.親子が達成できる緩やかな枠組みの食事療法に変更し,改善した.親子が主体的に食事療法に関われるよう介入したことなどが健康な食欲や食事療法に取り組む意欲を生んだと考えた.化学療法中には,現病や治療に伴う食欲低下だけでなく,心理面に留意した対応が重要であると考えた.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本小児心身医学会  

症例は14歳男性で,骨髄異形成症候群に対し造血幹細胞移植を受けた.その後,腸管の移植片対宿主病による腹痛が持続し,各種鎮痛薬を用いても改善が乏しいため心因の関与が疑われ,小児心身医療科に紹介された.移植片対宿主病による腸管狭窄から腹痛が生じていると考えられ,狭窄部切除術を実施されたが,さらに痛みの訴えが増強した.痛みや合併症の再発に対する不安,スタッフに十分に傾聴されていないという不満などの心因の関与により症状が遷延したと考えられたため,支持的カウンセリングに加えて多職種カンファレンスを行い,痛みの訴えへの対応方法を統一した.また,リハビリや食事の際に『できたこと』を肯定し行動を活性化させることにより,腹痛の訴えは軽減した.慢性の痛みがあると,痛みだけでなく痛みにまつわる気分や考えにより行動が左右され痛みの悪循環が発生することがある.この痛みの悪循環を断つためには,基礎疾患に対する身体的治療だけでなく,心理的サポートを行う必要がある.慢性疼痛には,多職種が協力し,心理的アセスメントとそれに基づいた一貫した対応によってチームアプローチを行うことが有効である.(著者抄録)

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

DOI： 10.1186/s12887-022-03706-3

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本小児栄養消化器肝臓学会  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

DOI： 10.3390/children9081253

PubMed

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

DOI： 10.1186/s12889-022-13899-y

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Children born preterm may be less physically active than children born term because of neurocognitive problems, reduced lung function, and poor physical fitness. We evaluated sports participation of children and adolescents who had been born preterm (<37 weeks) and early term (37-38 weeks) in 2001. METHODS: Data from a nationwide longitudinal survey (n = 47,015, including 2375 children born preterm) were analyzed. As indicators of sports participation, we used responses to questions about participation in sports clubs at 7 and 10 years old and in extracurricular school sports at 15 years old. RESULTS: Children born very preterm (25-31 weeks) and moderately to late preterm (32-36 weeks) were less likely to participate in sports clubs at 7, 10, and 15 years old than children born full term (39-41 weeks). Compared with children born full term, the adjusted risk ratios for participation in extracurricular school sports at 15 years old were 0.86 (95% confidence interval: 0.75-0.98) for children born very preterm, 0.92 (0.88-0.97) for children born moderately to late preterm, and 1.00 (0.98-1.02) for children born early term. CONCLUSIONS: Our findings suggest that preterm birth is associated with less participation in organized sports during childhood and adolescence than full-term birth. IMPACT: Research investigating associations between preterm birth and physical activity among children born in the 2000s is limited. This study shows that preterm birth was associated with less participation in organized sports during childhood and adolescence than full-term birth, especially in boys, and the participation in organized sports of children born preterm decreased as gestation shortened. During childhood, boys born early term were also less likely to participate in organized sports than boys born full term, suggesting a continuum with preterm births. These findings offer important additional insights into the limited evidence available for predicting future health outcomes for preterm infants.

DOI： 10.1038/s41390-021-01808-9

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. METHODS: We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. RESULTS: In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. CONCLUSIONS: Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. IMPACT: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.

DOI： 10.1038/s41390-021-01780-4

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記述言語：日本語   出版者・発行元：日本小児高血圧研究会  

【背景】一過性の著明な血圧上昇をきたし種々の身体症状を呈する症例において,褐色細胞腫の可能性は考慮する必要があるが,偽性褐色細胞腫との鑑別を要することもある.他方,その他の疾患と悩まれることは多くないが,今回我々は本態性高血圧に加えて精神的要因が関与したことにより褐色細胞腫に類似した症状を呈した症例を経験したため報告する.【症例】生来健康な男児で肥満はなかった.15歳時に学校で誘因なく発作的に胸部違和感を自覚した後上肢の脱力をきたし,更に意識混濁した.その際に保健室で測定された収縮期血圧は200mmHgを超えていた.同様のエピソードを反復したため当院に紹介された.来院時の血圧は140-150/70-80mmHg程度であった.問診では,学校生活での強い心理的ストレスの他,塩分摂取過多が疑われた.鑑別疾患として褐色細胞腫や偽性褐色細胞腫も考えられたが,意識混濁の身体症状を伴ったためてんかんの可能性も検討した.メタネフリンやカテコラミンの測定値や画像検査で異常はなく,上記エピソードが起こった際の心電図や脳波所見にも異常はなかった.他方,brachial-ankle Pulse Wave Velocityは両側とも高値であった.また,意識混濁を含む身体症状は精神科より解離性障害が疑われた.これらのことから,本態性高血圧が背景にあり,精神的要因が加わって一過性に高血圧になった可能性を考えた.食事指導とアムロジピンを少量から開始し増量した他,精神科からはクロチアゼパムが処方された.その後しばらくは,上記と同様のエピソードを繰り返し何度か当院に救急搬送されたが,次第に症状は落ち着いた.【考察】本症例は,褐色細胞腫に類似した症状を呈したが,身体症状として意識混濁を伴った点も特徴的であった.意識混濁は褐色細胞腫や偽性褐色細胞腫の身体症状としては考えにくく,てんかん性疾患も考えたが否定的であった.精神的要因で身体症状を伴って一過性に高血圧を呈することはあるが,その際の血圧上昇の程度は軽度とされている.このため,精神症状のみでは本症例の症状を説明できなかったが,本態性高血圧が背景にあり,解離様の精神症状が加わったことで褐色細胞腫類似の症状を呈したものと考えることで症状が説明づけられた.(著者抄録)

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記述言語：日本語   出版者・発行元：日本小児高血圧研究会  

酸化ストレスは、内部・外部刺激により生体内で活性酸素群(活性窒素も含む)が抗酸化システムで捕捉しきれないほど過剰に生じる状況である。酸化ストレス亢進は血管内皮障害と深く関連する。とりわけ、血管内皮での一酸化窒素(nitric oxide:NO)生成は生体のレドックス環境を保持するうえで必須である。酸化ストレス亢進はarginineを基質とするNO合成を抑制し、内因性NO合成酵素阻害因子であるasymmetric dimethylarginine(ADMA)の生成を刺激する。新生児の急速進行性疾患、慢性遷延性疾患ではしばしば酸化ストレスが増幅され、生体の構造や機能が酸化劣化を受けて、組織障害が不可逆的に進展する。これらの疾患の治療や管理において酸化ストレスを制御することは重要である。そのためには酸化ストレスの病態生理、それへの防御機制を把握し、特異的マーカーを用いて患者の酸化ストレス環境を非～低侵襲的に評価することが必要である。新生児医療の現場で実施される種々の治療は、酸化ストレス制御を目指すものでもある。その中で、母乳はNO、thioredoxin-1などの抗酸化因子を多量に含有し、酸化ストレス過剰病態の抑止に有効と推定される。今後は、"レドックス"に関連してより特異性の高い細胞機能修飾薬が開発され、それらが重症疾患への集学治療の中に組み込まれていくことが期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：日本小児心身医学会-中国四国地方会  

抜毛症は、繰り返し体毛を抜くことと、これを減らそう・やめようとする試みが特徴の、身体に焦点化した反復行動である。学童期から思春期に多く、抜毛によって満足や快感、安心感を得ることがあるとされる。本報告では、抜毛症女子の親子並行面接過程を振り返り、治療の意義を考察する。患児は、学校で過剰適応な行動が指摘されており、面接でも自分の希望を言うことは少なかった。治療が進むにつれて自ら遊びを選ぶなどの自己表現が増えた。また、箱庭療法や遊戯療法で繰り返し「家」を表現し、環境への信頼を獲得した。母は、心療内科治療歴があり、育児困難感や夫婦関係の問題を抱えていた。母面接では、抜毛の背景を説明し、母の苦労を傾聴しながら、母の対応や患児の変化を肯定的にフィードバックした。患児は学校でも自己主張が可能となり、抜毛は減少した。母も患児の成長を語るようになった。親子並行面接の構造と家族支援の視点が母子を支えたと考えた。(著者抄録)

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担当区分：最終著者   記述言語：英語  

DOI： 10.1038/s41598-022-11823-3

PubMed

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/archdischild-2021-322953

PubMed

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記述言語：日本語   出版者・発行元：岡山医学会  

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記述言語：日本語   出版者・発行元：岡山医学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00175&link_issn=&doc_id=20220415230008&doc_link_id=10.4044%2Fjoma.134.48&url=https%3A%2F%2Fdoi.org%2F10.4044%2Fjoma.134.48&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of β-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.

DOI： 10.1038/s41598-022-08791-z

PubMed

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

症例は全身性エリテマトーデスの18歳女性。タクロリムス(TAC)、ミコフェノール酸モフェチル(MMF)併用下に寛解状態にあった。急性胃腸炎を機に腎機能が低下し、いったん軽快した下痢の再燃および血球減少を認めた。TAC、MMF相互の副作用により両薬剤の血中濃度が上昇し有害事象が出現したと考えられ、TAC減量により症状は改善した。TAC、MMF2剤併用中に胃腸炎に罹患したときには、特異な血中濃度の変動に注意する必要がある。(著者抄録)

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

High-dose steroids are required for the treatment of minimal change nephrotic syndrome (MCNS), especially for episodes of recurrence. Predicting and avoiding recurrence can help reduce the steroid dose, but prediction is currently difficult. We herein examined whether changes in laboratory data, especially the urinary protein- to-creatinine ratio (UTP/UCr), can predict clinical recurrence. We also assessed differences in clinical features between children and young adults. We included 36 patients with MCNS; for each case, we retrospectively studied laboratory data during stable remission and pre-recurrence, with the "stable" period defined as all but the 6 weeks before recurrence, and pre-recurrence defined as the 4±2 weeks before recurrence. UTP/UCr, serum albumin, etc. were measured every 5 years during stable periods. We divided patients into cohorts by age at recurrence, < 15 years and ≥ 15 years, and compared stable and pre-recurrence values for the two groups. UTP/UCr values during stable periods tended to be higher in younger patients. UTP/UCr and serum albumin showed statistically significant changes during pre-recurrence periods, but only in those aged ≥ 15 years. Thus, clinical features of recurrence differed depending on age. Signs of recurrence can be confirmed via UTP/UCr or serum albumin several weeks before recurrence in patients ≥ 15 years.

DOI： 10.18926/AMO/63207

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1297/cpe.2021-0034

PubMed

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担当区分：最終著者   記述言語：英語  

Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.

DOI： 10.1002/ajmg.a.62478

PubMed

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

DOI： 10.1177/03000605211070492

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担当区分：責任著者   記述言語：英語  

Fibrodysplasia ossificans progressiva (FOP) is a rare skeletal disorder characterized by congenital malformation of the great toes and progressive heterotopic ossification. Malformation of the great toes appears at birth, while heterotopic ossification generally occurs during childhood and rarely occurs during infancy. Classical FOP results from the heterozygous p.Arg206His variant of the ACVR1 gene, which encodes Activin A receptor type 1. Recently, some atypical FOP patients with other ACVR1 gene variants and clinical features that are not observed in classical FOP patients have been reported. Herein, we describe a girl with severe FOP and multiple anomalies, including syndactyly of the hands and feet, nail agenesis, mandibular hypoplasia, heterotopic ossification occurring from infancy, and congenital cardiac malformation. In our patient, we identified de novo occurrence of the heterozygous p.Arg258Gly variant of ACVR1, which has previously been reported in only two severe FOP patients. Heterotopic ossification occurred earlier and more frequently compared with classical FOP patients. We present the time-series changes in heterotopic ossification in our patient and compare her clinical features with those of the previously reported patients with p.Arg258Gly. Our report deepens understanding of the clinical features in severe FOP with p.Arg258Gly and of FOP as a systemic disorder.

DOI： 10.1155/2022/5021758

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). METHODS: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. RESULTS: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. CONCLUSION: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

DOI： 10.1007/s00011-021-01496-5

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change.

DOI： 10.1038/s41598-021-02464-z

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as "atopic march". Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

DOI： 10.3390/children8111067

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: No relationship has been reported between nonopiate neonatal abstinence syndrome (NAS) and anthropometric indices, including head circumference (HC). The purpose of this study was to determine the relationship between maternal nonopioid drug use and HC at birth in neonates with NAS. METHODS: This retrospective observational study included neonates born between January 1, 2010 and March 31, 2019, whose mothers had been taking antipsychotic, antidepressant, sedative, or anticonvulsant medications. The outcome measures were HCs of NAS infants and controls. RESULTS: Of 159 infants, 33 (21%) were diagnosed with NAS. There was no maternal opioid use among mothers during pregnancy. The HCs in the NAS group were significantly smaller than those in the control group. The median z-scores for HC at birth were -0.20 and 0.29 in the NAS group and the control group, respectively (P = .011). The median HCs at birth were 33.0 and 33.5 cm in the NAS group and the control group, respectively. Multivariate analysis revealed that maternal antipsychotic drug use and selective serotonin reuptake inhibitors were independently associated with NAS (P < .001 and P = .004, respectively). Notably, benzodiazepine use and smoking were not independent risk factors. CONCLUSIONS: The results suggest an association between maternal antipsychotic drug use and NAS, which was further associated with decreased HC. Careful monitoring of maternal drug use should be considered to improve fetal outcomes.

DOI： 10.1017/S1092852920001522

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The respiratory system is continuously exposed to endogenous and exogenous oxidants. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, leading to the destruction of lung parenchyma (emphysema) and declining pulmonary function. It is increasingly obvious that reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the progression and amplification of the inflammatory responses related to this disease. First, we described the association between cigarette smoking, the most representative exogenous oxidant, and COPD and then presented the multiple pathophysiological aspects of ROS and antioxidative defense systems in the development and progression of COPD. Second, the relationship between nitric oxide system (endothelial) dysfunction and oxidative stress has been discussed. Third, we have provided data on the use of these biomarkers in the pathogenetic mechanisms involved in COPD and its progression and presented an overview of oxidative stress biomarkers having clinical applications in respiratory medicine, including those in exhaled breath, as per recent observations. Finally, we explained the findings of recent clinical and experimental studies evaluating the efficacy of antioxidative interventions for COPD. Future breakthroughs in antioxidative therapy may provide a promising therapeutic strategy for the prevention and treatment of COPD.

DOI： 10.3390/antiox10101537

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Jellyfish stings are known to induce allergic skin reactions; however, case reports of anaphylaxis after jellyfish ingestion have been increasing, especially in Asian countries. Some cases of anaphylaxis after jellyfish ingestion have been reported in patients with a previous history of frequent jellyfish stings. Herein, we report a pediatric patient with anaphylaxis after jellyfish ingestion with no history of jellyfish stings. CASE PRESENTATION: A 14-year-old girl developed two episodes of anaphylaxis, and her diet diaries revealed that edible jellyfish was common to the meals in both the anaphylaxis events. A skin prick test using five types of edible jellyfish products revealed a positive reaction to some jellyfish, and anaphylaxis was observed after the ingestion of jellyfish in an oral food challenge test. She had no history of jellyfish stings or frequent swimming in the ocean. The basophil activation test showed positive results on stimulation with extracts from various types of edible jellyfish. We observed serum immunoglobulin E (IgE) reactivity to purified jellyfish collagen and jellyfish acid-soluble extracts. Moreover, immunoblotting analysis showed IgE reactivity to two bands at approximately 40 and 70 kDa using purified jellyfish collagen, which may be a causative antigen. CONCLUSIONS: Edible salted jellyfish can be one of the causative foods of anaphylaxis. Clinicians should be aware of the possibility of anaphylactic reactions due to jellyfish ingestion even without a history of jellyfish stings.

DOI： 10.1186/s13223-021-00601-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dental caries is the most common chronic childhood disease. Recent studies have suggested that dental caries harbor respiratory infections in adults. We investigated the association between dental caries and influenza in children. In this study, 42,812 children aged 2.5 years, 38,540 children aged 5.5 years, and 34,124 children aged 10 years were included in the analysis from the Longitudinal Survey of Newborns in the 21st Century in Japan, which targeted all children born during a certain period in 2001. We used information on dental caries treated at hospitals and clinics in the past year as exposure and influenza as outcome during the observation periods (1.5-2.5, 4.5-5.5, and 9-10 years of age). We performed a log-binomial regression analysis, adjusting for potential confounders, and stratified analysis according to previous dental caries status. The presence of dental caries increased the incidence of influenza in all three target ages compared with the absence of dental caries. The incidence of influenza increased with the presence of current dental caries, regardless of the presence of past dental caries. These associations were observed irrespective of household income. Early detection and treatment of dental caries may reduce the risk of influenza in children.

DOI： 10.3390/children8090780

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記述言語：日本語   出版者・発行元：(一社)日本環境感染学会  

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記述言語：日本語   出版者・発行元：(一社)日本環境感染学会  

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記述言語：日本語   出版者・発行元：(一社)日本環境感染学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks' gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency.

DOI： 10.18926/AMO/62403

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記述言語：日本語   出版者・発行元：(一社)日本アレルギー学会  

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記述言語：日本語   出版者・発行元：(株)北隆館  

インフルエンザ脳症はインフルエンザ感染を契機にけいれんや意識障害を伴う。その病態は高サイトカイン血症による血液脳関門の障害が起きることで結果的に脳浮腫に至る。インフルエンザ脳症児の血液では特に「自然免疫」に関連した反応が強く起き、自然免疫メディエーターであるHigh Mobility Group Box-1(HMGB-1)は、インフルエンザ脳症児の血液中で高値を示す。岡山大学小児科では、インフルエンザ脳症における宿主の過剰な自然免疫反応を制御し、脳障害を軽減する次世代の炎症抑制療法の一つとして、HMGB-1をターゲットとした抗体治療の研究開発に取り組んでいる。(著者抄録)

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Osteogenesis imperfecta (OI) is a rare connective-tissue disorder characterized by bone fragility. Approximately 90% of all OI cases are caused by variants in COL1A1 or COL1A2. Additionally, IFITM5 variants are responsible for the unique OI type 5. We previously analyzed COL1A1/2 variants in 22 Japanese families with OI through denaturing high-performance liquid chromatography screening, but our detection rate was low (41%). METHODS: To expand the genotype-phenotype correlations, we performed a genetic analysis of COL1A1/2 and IFITM5 in 96 non-consanguineous Japanese OI probands by Sanger sequencing. RESULTS: Of these individuals, 54, 41, and 1 had type 1 (mild), type 2-4 (moderate-to-severe), and type 5 phenotypes, respectively. In the mild group, COL1A1 nonsense and splice-site variants were prevalent (n = 30 and 20, respectively), but there were also COL1A1 and COL1A2 triple-helical glycine substitutions (n = 2 and 1, respectively). In the moderate-to-severe group, although COL1A1 and COL1A2 glycine substitutions were common (n = 14 and 18, respectively), other variants were also detected. The single case of type 5 had the characteristic c.-14C>T variant in IFITM5. CONCLUSION: These results increase our previous detection rate for COL1A1/2 variants to 99% and provide insight into the genotype-phenotype correlations in OI.

DOI： 10.1002/mgg3.1675

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

In Japan, clinical and experimental studies addressing COVID-19 have been increasing in number since early February 2020, with many case reports being published. Concurrently, many notifications and guidelines have been issued from the government and academic societies. Taking optimal measures at the prefectural level as well as the national level is necessary to prevent the spread of COVID-19. Surveying and analyzing details of the incidences of infected persons in each prefecture is extremely important. This report describes the epidemiological characteristics of COVID-19 observed in Okayama Prefecture, followed by discussion of the direction of public health actions to be taken in the future. We reiterate the crucial importance of reinforcing and maintaining current public health measures, including rapid and detailed compilation of information related to infected persons and their surroundings, appropriate blocking of viral transmission, and early containment of infected persons, to minimize the spread of infection especially during the overlapping epidemic period of influenza in Okayama Prefecture.

DOI： 10.35772/ghm.2020.01104

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bovine jugular vein (BJV) and expanded polytetrafluoroethylene (ePTFE) conduits have been described as alternatives to the homograft for right ventricular outflow tract (RVOT) reconstruction. This study compared RVOT reconstructions using BJV and ePTFE conduits performed in a single institution. The valve functions and outcomes of patients aged < 18 years who underwent primary RVOT reconstruction with a BJV or ePTFE conduit between 2013 and 2017 were retrospectively investigated. 44 patients (20 and 24 with BJV and ePTFE conduits, respectively) met the inclusion criteria. The mean follow-up time was 4.5 ± 1.5 years. No significant differences in peak RVOT velocity (1.8 ± 0.9 m/s vs 2.1 ± 0.9 m/s, P = 0.27), branch pulmonary stenosis (P = 0.50), or pulmonary regurgitation (P = 0.44) were found between the BJV and ePTFE conduit groups, respectively. Aneurysmal dilatation of the conduit was observed in 25.0% of the patients in the BJV conduit group but not in the ePTFE conduit group (P = 0.011). All the cases with aneurysmal dilatation of the BJV conduit were complicated with branch pulmonary stenosis up to 3.0 m/s (P = 0.004). No conduit infections occurred during the follow-up period, and no significant difference in conduit replacement (20.0% vs 8.3%, P = 0.43) was found between the BJV and ePTFE conduit groups, respectively. The outcomes of the RVOT reconstructions with BJV and ePTFE conduits were clinically satisfactory. Aneurysmal dilatation was found in the BJV conduit cases, with branch pulmonary stenosis as the risk factor.

DOI： 10.1007/s00246-020-02458-0

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担当区分：最終著者   記述言語：英語  

Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner.

DOI： 10.18926/AMO/61215

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Tacrolimus is converted from intravenous to oral formulation for the prophylaxis of graft-versus-host disease when patients can tolerate oral intake and graft-versus-host disease is under control. Oral tacrolimus formulation presents poor bioavailability with intraindividual and interindividual variations; however, some factors affecting its blood concentration among pediatric hematopoietic stem cell transplantation (HCT) recipients are still unclear. This study aimed to identify the clinical factors affecting tacrolimus blood concentrations after switching its formulation. METHODS: Changes in the blood concentration/dose ratio (C/D) of tacrolimus in pediatric HCT recipients were analyzed after the switching of tacrolimus from intravenous to oral formulation. Clinical records of 57 pediatric patients who underwent allogenic HCT from January 2006 to April 2019 in our institute were retrospectively reviewed. The C/D of tacrolimus before discontinuation of intravenous infusion (C/Div) was compared with the tacrolimus trough level within 10 days after the initiation of oral administration (C/Dpo). Multiple linear regression analysis was performed to identify factors affecting (C/Dpo)/(C/Div). RESULTS: The constant coefficient of (C/Dpo)/(C/Div) was 0.1692 [95% confidence interval (CI), 0.137-0.2011]. The concomitant use of voriconazole or itraconazole and female sex were significant variables with a beta coefficient of 0.0974 (95% CI, 0.062-0.133) and -0.0373 (95% CI, -0.072 to -0.002), respectively. CONCLUSIONS: After switching of tacrolimus formulation, pediatric HCT recipients might need oral tacrolimus dose that is 5-6 and 3.5-4.5 times the intravenous dose to maintain tacrolimus blood concentrations and area under the concentration-time curve, respectively. With the concomitant use of voriconazole or itraconazole, an oral tacrolimus dose of 4-5 times the intravenous dose seemed appropriate to maintain blood tacrolimus concentration.

DOI： 10.1097/FTD.0000000000000793

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担当区分：最終著者   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Singapore  

DOI： 10.1007/978-981-15-9109-9_12

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To examine the association of specific Z-score categories of birth weight for gestational age with child health and neurodevelopment using a large nationwide survey in Japan, focusing on term infants. STUDY DESIGN: We included 36 321 children born in 2010. Hospitalization up to 66 months of age was used as an indicator of health status, and responses to questions about age-appropriate behaviors at 30 and 66 months of age were used to indicate neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for child and parental variables. A restricted cubic spline function was used to model the relationship. RESULTS: Compared with children with birth weight appropriate for gestational age (-1.28 to 1.28 SDs of expected birthweight for gestational age), children who were small for gestational age (SGA) (<-1.28 SD) had higher risks of hospitalization and unfavorable neurobehavioral development, and the risks increased as SGA status became more severe. Compared with the appropriate for gestational age group, the adjusted risk ratios for hospitalization for all causes were 2.5 (95% CI, 1.7-3.6), 1.3 (95% CI, 1.1-1.6), and 1.1 (95% CI, 1.0-1.2) for children who were severely, moderately, and mildly SGA and 1.0 (95% CI, 0.9-1.1), 1.1 (95% CI, 0.9-1.2), and 1.4 (95% CI, 0.9-2.1) for children who were mildly, moderately, and severely large for gestational age, respectively. Severely large for gestational age children also had higher risks of unfavorable neurobehavioral development. These results were supported by spline analyses. CONCLUSIONS: Among term infants, the risks of unfavorable child health and neurodevelopment increased with the severity of SGA.

DOI： 10.1016/j.jpeds.2020.06.075

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記述言語：英語  

Polydactyly is one of the most common foot congenital anomalies. It is often detected immediately after birth, but the diagnosis can sometimes be delayed if the symptoms are less evident. A 2-year-old girl with a complaint of recurrent bleeding from the right toenail was diagnosed with foot polydactyly. She underwent corrective surgery, and her family was satisfied with the outcome. Although the diagnosis of polydactyly may be difficult in cases with minor nail problems, further radiographic evaluation will be needed for the improvement of the patient's quality of life.

DOI： 10.18926/AMO/60803

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記述言語：日本語   出版者・発行元：日本臨床ウイルス学会  

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担当区分：最終著者   記述言語：英語  

DOI： 10.1002/pbc.28323

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記述言語：日本語   出版者・発行元：(一社)日本小児心身医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/jha2.24

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jha2.24

担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Renal calcified lesions are known as one of the complications during adrenocorticotropic hormone (ACTH) therapy for intractable epilepsy. However, laboratory changes during the therapy or laboratory features of high-risk cases with renal calcified lesions are yet to be clarified. METHODS: In this study, 43 patients with West syndrome aged ≤2 years were included. We retrospectively reviewed age and body mass index at the beginning of ACTH therapy, as well as the amount of fluid intake, daily urinary volume, and laboratory data during therapy. In addition, we studied the urinary sediment of the cases with renal calcified lesions diagnosed by computed tomography. RESULTS: After initiating ACTH treatment, urinary calcium (Ca)/creatinine ratio and urinary pH increased within 2 weeks. Urinary crystals and renal tubular epithelial cells (RTECs) in urinary sediment were frequently found in most cases. Urinary Ca levels, proteinuria or frequency of urinary crystals, and number of RTECs in the urinary sediment were significantly higher in patients with epithelial casts (ECs) or hematuria than in patients without these findings. Among the seven patients who underwent abdominal CT, ECs or hematuria were found only in those with renal calcified lesions. These findings suggested that patients with ECs or hematuria were more likely to have calcified lesions. CONCLUSIONS: The risk of renal calcified lesions increased after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy.

DOI： 10.1111/ped.14158

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記述言語：日本語   出版者・発行元：(一社)日本小児腎臓病学会  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). CASE PRESENTATION: An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. CONCLUSIONS: It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

DOI： 10.1186/s12887-020-1915-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although breastfeeding has been well-established as the preferred method for infant nutrition, its prophylactic effects on food allergy remain controversial. Infantile eczema has been linked to food allergy via percutaneous sensitization; however, this relationship has not been considered in previous studies. We aimed to uncover the prophylactic effects of breastfeeding on food allergy, focusing on eczema-mediated percutaneous sensitization. METHODS: This retrospective cohort study was based on 46,616 children from the Longitudinal Survey of Newborns in the 21st Century in Japan, begun in 2001. We classified participants into three groups based on infant feeding practices (exclusive breastfeeding, partial breastfeeding including only colostrum, and formula feeding only) and used information from at least one outpatient visit for food allergy during two observation periods (age 6-18 months and age 6-66 months) as health outcomes. We performed log-binomial regression analysis adjusted for potential confounders and stratified analysis according to infantile eczema status. RESULTS: Compared with formula feeding, partial breastfeeding including only colostrum reduced the risk of food allergy only in children with infantile eczema, (RR = 0.66, 95% CI: 0.46, 0.96 for age 6-66 months), whereas exclusive breastfeeding increased this risk in those without infantile eczema (RR = 2.41, 95% CI: 1.40, 4.15, age 6-66 months). The prophylactic effects of breastfeeding on food allergy in the infantile eczema group increased with shorter breastfeeding duration. CONCLUSIONS: Our results showed that breastfeeding, especially colostrum, had prophylactic effects on food allergy only among high-risk children with infantile eczema whereas prolonged breastfeeding increased the risk of food allergy.

DOI： 10.1016/j.alit.2019.08.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare bleeding disorder caused by antiprothrombin antibodies. LAHPS is associated with systemic lupus erythematosus (SLE) or infections. We describe two Japanese brothers with immunoglobulin-A vasculitis (IgAV) who met the diagnostic criteria of LAHPS. They presented with palpable purpura and abdominal pain, and had a prolonged activated partial thromboplastin time (APTT) and prothrombin deficiency with the presence of lupus anticoagulant. Pediatric LAHPS was reviewed in abstracts from the Japan Medical Abstracts Society that were written in Japanese and PubMed or Web of Science-listed articles in English between 1996 and 2019. Including our cases, pediatric LAHPS has been reported in 40 Japanese and 46 non-Japanese patients. We summarized the clinical and laboratory characteristics of all 86 cases, and found only one Japanese LAHPS case with IgAV, except for our cases. Of the 86 cases, most were associated with infections followed by SLE. The presence of SLE, older age, lower prothrombin levels, severe bleeding symptoms, and positivity of immunoglobulin G anticardiolipin antibodies and anticardiolipin/β2-glycoprotein I antibodies and/or β2-glycoprotein I-dependent anticardiolipin antibodies had higher odds of requiring treatment. Measuring the APTT and prothrombin time (PT) might be required in patients with IgAV when they do not have a typical clinical course or distinctive symptoms. LAHPS should be considered with prolongation of the APTT and/or PT. Additionally, it is important to maintain a balance between the risk of thrombosis and hemorrhage when normalization of the PT and FII levels occurs in LAHPS cases under treatment.

DOI： 10.1007/s00296-019-04404-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pulmonary vein stenosis (PVS) is a condition with challenging treatment and leads to severe cardiac failure and pulmonary hypertension. Despite aggressive surgical or catheter-based intervention, the prognosis of PVS is unsatisfactory. This study aimed to assess the prognosis and to establish appropriate treatment strategies. METHODS: We retrospectively reviewed endovascular treatments for PVS (2001-2017) from the clinical database at the Okayama University Hospital. RESULTS: A total of 24 patients underwent PVS associated with total anomalous pulmonary venous connection and 7 patients underwent isolated congenital PVS. In total, 53 stenotic pulmonary veins were subjected to endovascular treatments; 40 of them were stented by hybrid (29) and percutaneous procedures (11) (bare-metal stent, n = 34; drug-eluting stent, n = 9). Stent size of hybrid stenting was larger than percutaneous stenting. Median follow-up duration from the onset of PVS was 24 months (4-134 months). Survival rate was 71 and 49% at 1 and 5 years, respectively. There was no statistically significant difference between stent placement and survival; however, patients who underwent bare-metal stent implantation had statistically better survival than those who underwent drug-eluting stent implantation or balloon angioplasty. Early onset of stenosis, timing of stenting, and small vessel diameter of pulmonary vein before stenting were considered as risk factors for in-stent restenosis. Freedom from re-intervention was 50 and 26% at 1 and 2 years. CONCLUSIONS: To improve survival and stent patency, implantation of large stent is important. However, re-intervention after stenting is also significant to obtain good outcome.

DOI： 10.1017/S1047951119001495

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/ped.13908

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Rashkind balloon atrial septostomy (BAS) can be challenging in infants with hypoplastic left heart syndrome (HLHS) and small atrial septal defect (ASD). METHODS: We retrospectively reviewed all infants with HLHS who underwent surgery and BAS between January 2006 and December 2015. The infants were divided into three groups: no BAS; catheter BAS; and open AS. Infants who underwent catheter BAS were divided into two groups based on atrial septal anatomy: standard and complex. RESULTS: Of the 70 patients, 57 (81%) underwent Glenn surgery. Subsequently, a significant difference in survival was observed: 86% (44/51), 91% (10/11), and 25% (2/8) in the no BAS, catheter BAS, and open AS groups, respectively (P = 0.0002). No significant difference was seen between the no BAS and the catheter BAS groups (P = 1.0). In the 56 patients who underwent catheterization after surgery, no intergroup differences in mean pulmonary artery pressure, pulmonary vascular resistance, or pulmonary artery index were found. We classified catheter BAS into standard (n = 5) and complex (n = 5) based on ASD location, and septum thickness. All patients in the standard group underwent complete Rashkind BAS, but in the complex group, only one patient underwent complete Rashkind BAS, with the remaining requiring initial static BAS (P = 0.048). Following septostomy, ASD size, ASD flow, and percutaneous oxygen saturation (SpO2 ) were not significantly different between the two groups. CONCLUSIONS: Catheter BAS is effective in infants with HLHS and a restrictive atrial septum. Infants with standard or complex atrial septum can achieve equivalent outcomes despite more patients often requiring static BAS.

DOI： 10.1111/ped.13716

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記述言語：英語  

Most cases of transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) resolve spontaneously; however, DS-TAM neonates with hydrops fetalis (HF) show poor clinical outcomes. We report three infants with DS-TAM and HF who were treated with exchange transfusion (ET) followed by low-dose cytarabine (LD-CA). All of them survived without developing liver failure, acute leukemia, or other serious adverse events. Our results suggest that this combination treatment with ET and LD-CA would be safe, tolerable and effective as an novel approach for DS-TAM patients with HF.

DOI： 10.18926/AMO/56655

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Kawasaki disease is the leading cause of acquired childhood heart disease in most developed countries, but the etiology of the disease is unknown. An aberrant immune response to some environmental triggers may play a role and involuntary exposure to tobacco smoke can alter immune functions. We thus prospectively examined the association between early childhood exposure to maternal smoking and the incidence of Kawasaki disease. We used a large, nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 38,444 children for whom information on maternal smoking was available. Maternal smoking status was ascertained at 6months of age, and responses to questions about hospital admission for Kawasaki disease between the ages of 6 and 30months were used as outcome. We conducted binomial log-linear regression analyses adjusting for children's, parental, and residential factors with children of non-smoking mothers as our reference group. Maternal smoking increased the risk of admission, in particular for the period between 6 and 18months of age, in a dose-dependent manner. Compared with children of non-smoking mothers, the children of mothers who smoked had a risk ratio of 1.83 (95% confidence interval: 1.06, 3.35) for hospital admissions between 6 and 30months of age and a risk ratio of 2.69 (95% confidence interval: 1.56, 4.64) for hospital admissions between 6 and 18months of age. Early childhood exposure to maternal smoking may increase the risk of Kawasaki disease hospitalizations in childhood.

DOI： 10.1016/j.scitotenv.2018.11.194

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

DOI： 10.1002/jmv.25330

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

DOI： 10.1007/s00277-018-3554-8

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: We examined the effects of being born small for gestational age (SGA) on the risk of being hospitalised for common diseases during childhood. METHODS: This Japanese nationwide, population-based longitudinal survey followed babies born before 42 weeks of gestation from 10 to 17 January and from 10 to 17 July 2001, using data from the Government's Longitudinal Survey of Babies in the 21st Century. Our study followed 41 268 children until 5.5 years of age: 39 107 full term (8.7% SGA) and 2161 preterm (15.5% SGA). We evaluated the relationship between SGA status and hospitalisation using their history of hospitalisation for common diseases and comparing full-term or preterm births. Logistic regression analysis, adjusted for potential confounders, estimated the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The full-term and preterm children who were born SGA were more likely to be hospitalised during infancy and early childhood than those born non SGA. The ORs for hospitalisation from six months to 18 months of age were 1.23 (95% CI: 1.10-1.37) for full-term and 1.67 (95% CI: 1.23-2.25) for preterm subjects. Higher risks of hospitalisation due to bronchitis, pneumonia, bronchial asthma and diarrhoea were also observed. CONCLUSION: Being born SGA was associated with all-cause and cause-specific hospitalisation in early childhood, particularly for term infants.

DOI： 10.1111/apa.14507

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記述言語：日本語   出版者・発行元：(一社)日本環境感染学会  

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記述言語：日本語   出版者・発行元：(一社)日本環境感染学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage. METHODS: Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls. RESULTS: The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and β-alanine were also found in the citrin-deficient children. CONCLUSION: The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism. SYNOPSIS: In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and β-alanine, were found by comparison to the age-matched healthy control children, and it suggested that the characteristic alteration of serum amino acids may be resulted from compensation for energy metabolism and ammonia detoxification.

DOI： 10.1007/8904_2018_99

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prevalence of multiple births has recently increased. However, the association between gestational age and long-term morbidity among twins remains unclear. AIMS: To examine the association of gestational age with child health and neurological development in early childhood among twins. STUDY DESIGN: Population-based longitudinal study. SUBJECTS: We included 947 children from 479 pairs of twins with information on gestational age. OUTCOME MEASURES: Hospitalization was used as an indicator of physical health, and responses to questions about age-appropriate behaviors were used as an indicator of neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for both child and maternal variables in the model. We accounted for correlations within the pairs with generalized estimating equations. RESULTS: The early term group (i.e., 37 to 38 weeks of gestation) had a lower risk of poor child health and unfavorable neurodevelopment compared with the full term group (≥39 weeks of gestation) and preterm group (<37 weeks of gestation). Compared with the early term group, the adjusted risk ratios for hospitalization for all causes during the period from 7 to 18 months of age was 2.2 (95% confidence interval: 1.3-3.8) for very preterm children (<32 weeks of gestation), 1.1 (0.8-1.6) for moderately and late preterm children (32 to 36 weeks of gestation), and 1.8 (1.0-3.2) for full term children. CONCLUSION: We observed a U-shaped association of gestational age with child health and neurodevelopment. The early term group had the lowest risk of poor outcomes among twins.

DOI： 10.1016/j.earlhumdev.2018.11.005

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

当科を受診した摂食障害患者のうち、発症が18歳未満の112例について検討した。その結果、診断は回避/制限性食物摂取障害(ARFID)が52例(46.4%)と多く、神経性やせ症(AN)や神経性過食症(BN)と比べて発症時年齢が低いこと、男児が多いこと、初診時の体重減少が少ないことなどの特徴がみられた。治療継続102例中、69例(67.6%)が寛解または軽快に至っており、小児科での治療に一定の効果を認めた。一方で、悪化による精神科転科は17例(9.8%)、治療終了後の再診は13例(12.7%)に上り、思春期症例への対応については課題が大きく、今後も検討を要すると考えられた。

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

[This corrects the article DOI: 10.1155/2018/2380179.].

DOI： 10.1155/2019/4025694

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The length of stay (LOS) in intensive care units (ICUs) has been used as a good indicator not only for resource consumption but also for health outcomes of patients. However, data regarding pediatric LOS in Japanese ICUs are limited. The primary aim of this study was to characterize the Japanese pediatric ICU patients based on their LOS. Second, we aimed to develop a simple scoring system to predict long-stay pediatric ICU patients on admission. Methods: We performed a retrospective cohort study using consecutive pediatric data (aged < 16 years) registered in the Japanese Registry of Pediatric Acute Care (JaRPAC) from October 2013 to September 2016, which consisted of descriptive and diagnostic information. The factors for long-stay patients (LSPs; LOS > 14 days) were identified using multiple regression analysis, and subsequently, a simple predictive scoring system was developed based on the results. The validity of the score was prospectively tested using data from the JaRPAC registration from October 2016 to September 2017. Results: Overall, 4107 patients were included. Although LSPs were few (8.0% [n = 330]), they consumed 38.0% of ICU bed days (9750 for LSPs versus 25,659 overall). Mortality was seven times higher in LSPs than in short-stay patients (9.1% versus 1.3%). An 11-variable simple predictive scoring system was constructed, including Pediatric Index of Mortality 2 ≥ 1 (2 points), liver dysfunction (non-post operation) (2 points), post-cardiopulmonary resuscitation (1 point), circulatory disorder (1 point), post-operative management of liver transplantation (1 point), encephalitis/encephalopathy (1 point), myocarditis/cardiomyopathy (1 point), congenital heart disease (non-post operation) (1 point), lung tissue disease (1 point), Pediatric Cerebral Performance Category scores ≥ 2 (1 point), and age < 2 years (1 point). A score of ≥ 3 points yielded an area under the receiver operating characteristic curve (AUC) of 0.79, sensitivity of 87.0%, and specificity of 59.4% in the original dataset. Reproducibility was confirmed with the internal validation dataset (AUC 0.80, sensitivity 92.6%, and specificity 60.2%). Conclusions: Pediatric LSPs possess a significant presence in Japanese ICUs with high rates of bed utilization and mortality. The newly developed predictive scoring system may identify pediatric LSPs on admission.

DOI： 10.1186/s40560-019-0392-2

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1297/cpe.28.155

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/ped.13615

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan.

DOI： 10.18926/AMO/56170

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context: Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia, which is associated with metabolic abnormalities. Objectives: To identify the causes of hypercholesterolemia in citrin-deficient children post-NICCD. Design and Setting: We determined the concentrations of sterol markers of cholesterol synthesis, absorption, and catabolism by liquid chromatography-electrospray ionization-tandem mass spectrometry and evaluated serum lipoprotein profiles. Subjects: Twenty citrin-deficient children aged 5 to 13 years and 37 age-matched healthy children. Intervention: None. Main Outcome Measures: Relationship between serum lipoproteins and sterol markers of cholesterol metabolism. Results: The citrin-deficient group had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than did the control group (78 ± 11 mg/dL vs 62 ± 14 mg/dL, P < 0.001), whereas the two groups had similar low-density lipoprotein cholesterol and triglyceride concentrations. The concentrations of markers of cholesterol synthesis (lathosterol and 7-dehydrocholesterol) and bile acids synthesis (7α-hydroxycholesterol and 27-hydroxycholesterol) were 1.5- to 2.8-fold and 1.5- to 3.9-fold, respectively, higher in the citrin-deficient group than in the control group. The concentration of 24S-hydroxycholesterol, a marker of cholesterol catabolism in the brain, was 2.5-fold higher in the citrin-deficient group. In both groups, the HDL-C concentration was significantly positively correlated with that of 27-hydroxycholesterol, the first product of the alternative bile acid synthesis pathway. Conclusions: HDL-C and sterol marker concentrations are elevated in citrin-deficient children post-NICCD. Moreover, cholesterol synthesis and elimination are markedly enhanced in the liver and brain of citrin-deficient children.

DOI： 10.1210/jc.2017-02664

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

DOI： 10.1002/jmv.25076

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

DOI： 10.1507/endocrj.EJ18-0008

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記述言語：日本語   出版者・発行元：日本小児高血圧研究会  

【背景】腎血管性高血圧は小児高血圧の主要な原因の一つと言われているが、乳児例の報告は少なく、また診断に時間を要することが多い。今回、生後3ヵ月頃から網状チアノーゼの症状を認めたレニン依存性高血圧の男児例を経験した。【症例】周産期には異常なかったが1ヵ月健診で体重増加不良、3ヵ月健診で網状チアノーゼを指摘され、心エコーで拡張型心筋症が疑われていた。経過中に胃腸炎に罹患した際、心不全の状態となり、同時に高血圧も認められた。入院後、心機能改善に伴い高血圧が増悪したため、高血圧性心疾患として原因検索したところ、血漿レニン活性およびアルドステロン高値の状態であった。造影CTでは両側に複数腎動脈が認められ、局所的な狭窄はなかったが、いずれの腎動脈も全長にわたって狭小であり、これらの血管による腎灌流圧の低下が病態の本態と考えた。その後、降圧薬2剤で血圧は良好にコントロールできるようになり、現在外来で経過観察されている。【考察】本症例は、レニン依存性高血圧の状態であり、腎血管性が疑われた。本症例と同様に、乳児期の腎血管性高血圧の症例は、症状が非特異的であり、心不全の状態で診断されることも多いため、注意を要する。また、病態も局所的な腎血管狭窄に限らず、腎灌流圧の低下をきたしうる病変を幅広く検討する必要がある。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本小児心身医学会  

小児の長期入院では、健康な心理社会的発達を促すための経験が減少することが問題となるが、発達障害を有する場合はとくに注意が必要である。今回、悪性疾患による長期入院中に発達特性が顕在化し対応した2症例を経験した。2例ともに入院前よりかんしゃくやこだわりなどの問題行動を認め、1例は発達支援が開始されていた。入院後、原病の治療への支障、付き添う母親の疲弊などを契機に支援を開始した。スタッフや家族から情報を収集し、行動観察や発達検査などで評価を行った後、児への療育的関わりや家族への疾病教育、スタッフとの情報共有と環境調整を行った。結果、問題行動の軽減や家族の精神的ストレスの緩和につながり、原病の治療が安全かつ円滑に行われ、退院後の発達支援も可能となった。発達の課題が疑われる児の入院の際には、その特性に配慮し退院後も継続可能な支援体制づくりを行うことが重要である。(著者抄録)

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記述言語：日本語   出版者・発行元：日本小児心身医学会-中国四国地方会  

ボタン恐怖症に認知行動療法(Cognitive behavioral therapy:CBT)を実施しその有効性を検討した。症例は10歳男児。3歳頃大きなボタンを見てから、「ボタンを見ると気分が悪くなる」と訴えてボタンを避けるようになった。転校後、制服のボタンが気になり嘔気が増えたため岡山大学病院小児科を受診した。疾病教育や認知再構成法を行い、約4ヵ月後にボタン恐怖は消失した。今回、特に動機づけなどに工夫を行うことで、子どもの不安・恐怖症状について認知行動療法を用いて治療することができた。(著者抄録)

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/cea.13100

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective The present study was performed to identify factors associated with a Bacille Calmette-Guérin (BCG) inoculation site change in patients with Kawasaki disease (KD). Methods Among patients who had received BCG vaccination and treatment for KD at our hospital from 2005 through 2016, 177 patients born in 2005 through 2016 were enrolled. The patients were divided into those with (n = 83, change group) and without (n = 94, no-change group) a BCG site change, and the patient demographics, clinical severity, blood examination results, and echocardiographic findings were compared between the two groups. Results The change group was younger at onset and had a shorter interval from vaccination to onset. A BCG site change was observed in patients who developed the onset of KD symptoms from 31 to 806 days after BCG vaccination. Multivariate analysis showed that the interval from vaccination was closely and positively associated with the BCG site change (hazard ratio = 0.995, 95% confidence interval = 0.993-0.997). Conclusion A BCG site change in patients with KD is most closely associated with the interval from BCG vaccination to onset.

DOI： 10.1177/0300060518760462

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications Ltd  

Objective: To investigate the basal amino acid metabolism and impact of growth hormone (GH) therapy in short-stature children born small for gestational age (short SGA children). Methods: In this age-matched case-control study, the basal blood levels of amino acids, asymmetric dimethylarginine (ADMA), and nitrite/nitrate (NOx) were compared between 24 short SGA children and 25 age-matched normal children. Changes in these parameters were assessed for 12 months in 12 short SGA children initiating GH therapy (Group A) and 12 age-matched short SGA children without GH therapy (Group B). Results: The arginine levels were significantly lower in the short SGA than in normal children. The ADMA levels were significantly higher and NOx levels were significantly lower in the short SGA than normal children. In Group A, the ADMA level was significantly lower and NOx level was significantly higher at 6 months than at baseline. At 12 months, the ADMA level in Group A began to increase, but the NOx level remained the same. Group B showed no significant changes. Conclusions: This study is the first to show that ADMA is promoted and nitric oxide is suppressed in short SGA children and that GH therapy affects the production of ADMA and nitric oxide.

DOI： 10.1177/0300060517723183

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To examine the effects of prenatal and postnatal exposure to particulate matter on Kawasaki disease (KD) occurrence, using data from a nationwide population-based longitudinal survey in Japan that began in 2010. STUDY DESIGN: Prenatal and postnatal suspended particulate matter concentrations were obtained at municipality level and assigned to participants based on their municipality of birth. We analyzed data from 30 367 participants with data on either exposure period. We used hospital admission for KD from 6 to 30 months of age as the main outcome of interest. We conducted a multilevel logistic regression analysis, adjusting for individual and municipality-level variables. RESULTS: Children who were exposed to higher levels of suspended particulate matter, in particular during pregnancy, were more likely to be hospitalized for KD. The ORs for ≥25 µg/m3 exposure compared with <20 µg/m3 exposure were 1.59 (95% CI 1.06, 2.38) for prenatal exposure and 1.41 (0.82, 2.41) for postnatal exposure. Prenatal exposure during mid-to-late gestation seemed to be more relevant for the increased risk. CONCLUSIONS: Early life exposure to particulate air pollution, in particular during pregnancy, is associated with an increased risk of KD hospital admission in early childhood in a nationally representative sample in Japan.

DOI： 10.1016/j.jpeds.2017.10.012

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-α, and IFN-γ) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 ± 6.7 and 0.8 ± 0.9, respectively (p = 0.0011). CRP (mg/dL) were 0.79 ± 0.89 and 1.4 ± 1.0 (p = 0.21), respectively; IL-6 (pg/mL) were 449.7 ± 705.0 and 118.3 ± 145.4 (p = 0.20), respectively; TNF-α (pg/mL) were 18.6 ± 12.5 and 16.6 ± 6.0 (p = 0.67), respectively; and IFN-γ (pg/mL) were 79.6 ± 158.5 and 41.9 ± 63.7 (p = 0.56), respectively. Ratios of PCT to CRP were 27.5 ± 34.2 and 3.2 ± 6.8 (p < 0.0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 100% and 80%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism.

DOI： 10.1155/2018/2380179

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with 22q11.2 deletion syndrome have characteristic facial appearance, palate abnormalities, hypoparathyroidism, thymic hypoplasia, and congenital heart disease. The 22q11.2 region includes TBX1 and 30 other genes. Analysis of Tbx1 transgenic mice showed that TBX1 was associated with the 22q11.2 deletion syndrome. In humans, TBX1 mutations have been reported in 22q11.2 deletion-negative patients with velocardiofacial syndrome or DiGeorge syndrome. Genotype-phenotype correlations are not fully understood in these patients. We report the case of an infant with a novel heterozygous TBX1 mutation who experienced hypocalcemic seizures. This patient had no palate abnormalities, cardiac anomalies, or the typical facial appearance observed in 22q11.2 deletion syndrome. The presence of thymic hypoplasia prompted us to perform G-banding, fluorescent in situ hybridization, and subsequent TBX1 analysis. We emphasize the importance of diagnosing thymic hypoplasia in hypocalcemic infants without 22q11.2 deletion for detecting TBX1 mutations.

DOI： 10.1297/cpe.27.159

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pediatric papillary thyroid carcinoma frequently presents with lymph node involvement and distant metastases. Sorafenib, an oral multikinase inhibitor, has been used to treat radioactive iodine (RAI) therapy-refractory thyroid carcinoma in adults; however, pediatric experience is limited. Medical procedures and hospitalization for children with autism spectrum disorder may be challenging. CASE PRESENTATION: An 11-year-old boy with autism spectrum disorder and moderate intellectual impairment presented with dyspnea on exertion with thyroid carcinoma and diffuses lung metastases. Total thyroidectomy and adjuvant RAI therapy is the standard treatment; however, the latter therapy was impractical because of his respiratory status and challenging behaviors. He was therefore started on sorafenib 200 mg/day (150 mg/m2/day) and this dosage was increased to 400 mg/day (300 mg/m2/day). The adverse effects were mild and tolerable. After administration of medication, his dyspnea improved and surgery was performed. We attempted to administer RAI therapy after surgery; however, we abandoned it because he had difficulty taking care of himself according to isolation room rules. Thyrotropin suppression therapy was therefore started and sorafenib treatment (400 mg/day) resumed. Follow-up imaging showed regression of pulmonary metastases. The metastases have remained stable for over 24 months on continuous sorafenib treatment without serious adverse events. CONCLUSION: We inevitably used sorafenib as an alternative to standard therapy because of the patient's specific circumstances. Individualized strategies for pediatric cancer patients with autism spectrum disorder are needed.

DOI： 10.1186/s12885-017-3782-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16(-)CD56(+)-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56brightCD16dim/- NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.

DOI： 10.1080/10428194.2017.1304762

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Childhood cancer survivors (CCS) and their family members continue to live in fear even after treatment is concluded due to concerns about late effects and recurrences. The consequent long-term psychological burden requires long-term follow up suited to the anxieties and needs of CCS, hence the need for the present survey. METHODS: We conducted a questionnaire survey at medical facilities in the Chugoku and Shikoku regions of Japan with CCS who had survived for at least 5 years following treatment, and their family members. RESULTS: A total of 30 CCS (53%) and 27 CCS family members (47%) answered the questionnaires. The median age of the CCS and their family members (CCS parents) was 23 years and 51.5 years, respectively. The most common diagnosis was acute lymphoblastic leukemia (47%) and the median length of follow up after the conclusion of treatment was 11 years. The percentage of participants who responded that they knew about late effects was significantly lower among CCS than among CCS parents. Almost no significant difference was observed between CCS and CCS parents regarding anxieties at specific life stages. The main consultants for CCS and CCS parents were their family, but they sought opportunities for casual consultation for current worries outside the family. CONCLUSIONS: It is necessary for medical facilities not only to provide medical support, but also to establish a place where they can provide centralized consultation for the anxieties of CCS and their parents.

DOI： 10.1111/ped.13390

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記述言語：日本語   出版者・発行元：(一社)日本小児心身医学会  

ドメスティックバイオレンス(以下DV)の目撃は虐待の一種で、子どもの心身に大きな影響をもたらす。今回われわれは、DV目撃後に不安症状を呈し、発達に課題のある2症例を報告する。いずれも、成育歴や心理検査で発達の偏りが示唆され、言語表現力、イメージ力の弱さが症状の遷延やその後の適応に影響していた。症例Aは、箱庭を使った感覚遊びを通して安心感を得て、日常生活のことを言語化した。症例Bは、箱庭の中で危機的な状況が徐々に整理されて安心感を獲得し、現実世界に向かった。言語的やりとりが活性化し、その中で父への気持ちも言語化できた。2症例ともに箱庭の箱という空間があり、安心して自由に表現できたことが、DV目撃後の不安症状の回復に効果的であった。また、生来の特徴として想像力の弱さがあり、抽象化しにくい児にとって箱庭療法が有効に働いた。箱庭療法から見立てた児の状態を母面接に活かし、治療効果を高めることができた。(著者抄録)

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記述言語：日本語   出版者・発行元：(NPO)日本小児循環器学会  

背景:左心低形成症候群(HLHS)では左房容積が小さく、心房中隔の形態や心房中隔欠損(ASD)の大きさによってRashkind Balloon Atrial Septostomy(BAS)を行うことが困難な場合もある。目的:当院におけるHLHSに対するBASの有効性について検討した。対象と方法:2006年1月から2015年12月までの10年間にHLHSに対してカテーテル治療・手術を施行した患者におけるBASの有効性について検討した。またcatheter BASを施行した群についてASDの形態別に分けて有効性について両群比較検討した。結果:全HLHS70例中のGlenn手術到達は57例(81%)であり、BAS未施行群では86%(44/51)、catheter BAS群では91%(10/11)、open BAS群では25%(2/8)と統計学的有意差を認めたが(p=0.0002)、BAS未施行群とcatheter BAS群では同等の結果であった。(p=1.0)Glenn手術後にカテーテル検査を施行した56例について検討すると、BAS未施行群、catheter BAS施行群、open BAS施行群の平均肺動脈圧、肺血管抵抗、PAIいずれも3群間に差は認めなかった。次にCatheter BAS施行群をASDの位置・大きさ・atrial septumの厚さからstandard ASD(n=5)、complex ASD(n=5)に分類し、ASDの形態別にBAS施行方法を検討すると、standard ASD群では全例Rashkind BAS単独施行で効果を得たが、complex ASD群ではRashkind BAS単独施行症例は1例のみで、Static BASを先行させRashkind BASに到達した症例が4例であった(p=0.048)。BAS後のASD size、ASD flow、SpO2は2群間で統計学的有意差を認めなかった。結論:catheter BASは有効で、Glenn後のカテーテルデータではBAS未施行群と有意差は認めなかった。またcomplex ASD群の場合には、Static BASを先行し、Rashkind BASを追加することで、standard ASD群と同等の効果を得ることができた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02003&link_issn=&doc_id=20180418180002&doc_link_id=%2Fee7shoni%2F2017%2F003306%2F003%2F0423-0430%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fee7shoni%2F2017%2F003306%2F003%2F0423-0430%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome. CASE PRESENTATION: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp). CONCLUSIONS: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

DOI： 10.1186/s13256-017-1396-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non-inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-α and IL-1β. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia.

DOI： 10.1016/j.bbrc.2017.05.172

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

BACKGROUND: Growth hormone (GH) replacement therapy improves hypercholesterolemia in patients with GH deficiency, suggesting that GH modulates cholesterol metabolism.
OBJECTIVES: We examined GH effects on lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism in small-for-gestational age (SGA) children without catchup growth.
METHODS: This study examined SGA children without catch-up growth (n = 22) and healthy children (controls, n = 11). Based on parents' choice, 11 SGA children received GH at 0.23 to 0.25mg/kg/d for 6 months, and at 0.34 to 0.36 mg/kg/d for the subsequent 6 months (GH (+) group). The other SGA children received no GH (GH (-) group, n = 11). We ascertained baseline and posttreatment lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism.
RESULTS: Baseline lipid profiles of SGA children and controls were similar. Serum 24S-hydroxycholesterol (marker for cerebral cholesterol metabolism) concentration was 19% lower in SGA children than in controls (P &lt; .05). Compared with baseline, the GH (+) group low-density lipoprotein -cholesterol concentration had decreased by 6.6% during 6 months and 8.8% during 12 months (P &lt;.01), whereas the high-density lipoprotein-cholesterol concentration had increased by 1.7% (P =.07) and 3.3% (P &lt; .01). Serum 7a-hydroxycholesterol (marker for hepatic cholesterol elimination) concentration had increased by 34% at 6 months and 35% at 12 months (P &lt; .01). In addition, 24S-hydroxycholesterol increased by 25% and 26% (P &lt; .001). No marker for cholesterol synthesis or absorption changed. The GH (-) group lipid profiles and oxysterols remained unchanged during the observation period.
CONCLUSION: GH activates hepatic and cerebral cholesterol metabolism in SGA children without catch-up growth. (C) 2017 National Lipid Association. All rights reserved.

DOI： 10.1016/j.jacl.2017.05.010

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その他リンク： http://orcid.org/0000-0002-4294-8030

記述言語：日本語   出版者・発行元：日本小児感染症学会  

EBV関連血球貪食性リンパ組織球症(EBV-HLH)の児で初発時にCD8陽性T細胞に感染していたが、再燃時にB細胞内に増殖を認めた症例を経験したので報告する。症例は2歳の女児であり、発熱と汎血球減少からEBV-HLHと診断された。EBV-DNA量と感染細胞のプロファイリングを行い、診断時にはEBV-DNA量の増加とCD8陽性T細胞への感染を確認した。本児にはHLH-2004プロトコールに準じて治療を開始した。全血EBV-DNA量は一時的に検出感度未満まで低下したが、治療終了直後に再度増加した。感染細胞のプロファイリングによりB細胞内へのEBV感染が疑われた。EBV-HLHの再発例では造血幹細胞移植を行うこともあるが、感染細胞の同定によりB細胞への感染が考えられたためリツキシマブを使用し、EBV-DNA量は速やかに検出感度未満となった。EBV-DNA定量と感染細胞の同定はEBV-HLHの治療方針の決定に有用であると考えられた。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although dosing and sizing of resuscitation drugs and equipment are mostly weight based, time is usually insufficient to weigh critically ill children. Many age-based weight estimation formulae for emergency use have been developed worldwide, but there is no specific formula for Japanese children. The aim of this study was therefore to develop and validate age-based formulae for estimating the bodyweight of children living in Japan. METHODS: A total of 370 980 measurements of bodyweight were obtained from 39 547 participants aged 12-155 months. They participated in a national survey, called the Longitudinal Survey of Babies in the 21st Century, which started in 2001. We created the new original weight estimation formulae for children living in Japan, called the Japanese Pediatric Assessment of Normal weight (JAPAN) formulae, using 75% of measurements that were randomly selected from the total measurements. To check the validity of the formulae, we applied the JAPAN formulae, the Park et al. formula for Korean children, and the commonly used Nelson formula for the remaining 25% of measurements. The mean absolute error and the root mean square error (RMSE) were calculated for each scale. RESULTS: The JAPAN formulae performed better than the two other formulae among Japanese children, with a mean absolute error and RMSE of 0.83 and 1.08 (kg), respectively. The performance of the Park et al. formulae for Korean children was poor for children living in Japan. CONCLUSIONS: The newly developed JAPAN formulae for age-based weight estimation are appropriate for children living in Japan.

DOI： 10.1111/ped.13259

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記述言語：日本語   出版者・発行元：(一社)日本周産期・新生児医学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児心身医学会  

起立性調節障害(orthostatic dysregulation:以下OD)は、成人期にも何らかの症状が継続することが知られているが、高校進学後の社会適応については不明な点も多い。われわれは、18歳以上まで経過を観察した23例について治療過程を振り返り、進路選択とその課題について検討を行った。社会的転帰不良群の特徴として、初診時年齢が低い、2次障害として精神疾患の発症を認めるなどがあった。一方、社会適応が良好な症例でも起立試験の結果は改善せず、自覚症状が消失していない症例も多かった。社会的予後の改善には心理社会的なサポートを行いながら2次障害の発症に注意すること、症状と付き合いながら生活する能力を向上させることが重要と考えた。難治例、成人例に対して成人科への移行も含めた効果的な治療・対応法についてのさらなる検討が必要である。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management.

DOI： 10.18926/AMO/54987

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Citrin deficiency causes adult-onset type II citrullinemia (CTLN-2), which later manifests as severe liver steatosis and life-threatening encephalopathy. Long-standing energy deficit of the liver and brain may predispose ones to CTLN-2. Here, we compared the energy-driving tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation cycle between 22 citrin-deficient children (age, 3-13 years) with normal liver functions and 37 healthy controls (age, 5-13 years). TCA cycle analysis showed that basal plasma citrate and alpha-ketoglutarate levels were significantly higher in the affected than the control group (p &lt; 0.01). Conversely, basal plasma fumarate and malate levels were significantly lower than those for the control (p &lt; 0.001). The plasma level of 3-OH-butyrate derived from fatty acid (3-oxidation was significantly higher in the affected group (p &lt; 0.01). Ten patients underwent sodium pyruvate therapy. However, this therapy did not correct or attenuate such deviations in both cycles. Sodium pyruvate therapy significantly increased fasting insulin secretion (p &lt; 0.01); the fasting sugar level remained unchanged. Our results suggest that citrin-deficient children show considerable deviations of TCA cycle metabolite profiles that are resistant to sodium pyruvate treatment. Thus, long-standing and considerable TCA cycle dysfunction might be a pivotal metabolic background of CTLN-2 development. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ymgme.2016.12.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Behçet disease (BD) is rarely seen in children. Its clinical manifestations are believed to differ between pediatric and adult patients. The characteristics of BD complicated by myelodysplastic syndrome (MDS) are well established for adult patients; however, because only a few cases of pediatric-onset BD complicated by MDS have been reported, its clinical characteristics remain unknown. We here retrospectively review pediatric-onset BD complicated by myeloid malignancies in Japan, having identified five such patients. All patients were female and had gastrointestinal involvements, but lacked both major features of BD, i.e., uveitis and association with HLA-B51. All patients had advanced MDS or acute myeloid leukemia and received chemotherapy followed by hematopoietic stem cell transplantation. These five cases suggest that intestinal BD and myeloid malignancies have one or more pathophysiological mechanisms in common.

DOI： 10.1007/s12185-016-2127-7

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記述言語：英語  

Bordetella pertussis causes life-threatening apnea in infants. Lymphocytosis is an important clue for diagnosis and for determining the severity of pertussis. Antibiotics do not shorten or ameliorate the disease and only decrease the risk of transmission. Antepartum maternal immunization is important for preventing pertussis in infants.

DOI： 10.1002/ccr3.765

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Redox regulation has recently been recognized as an important factor in acute illnesses as well as in chronic diseases. It has also become a target for neuroprotection in acute intensive care. Despite its well-known therapeutic effects, therapeutic hypothermia has recently been re-evaluated for its potential use in emergency and critical care medicine. Hypothermia is an undesirable physiological condition that can increase oxidative stress and decrease anti-oxidative potency. However, many studies have shown that under ischemia/reperfusion conditions, therapeutic hypothermia actually suppresses enhanced oxidative stress and maintains or increases anti-oxidative potency. This review provides an overview and outlook for the future of therapeutic hypothermia for neuroprotection from the perspective of redox regulation in patients with post-cardiac arrest syndrome and traumatic brain injury.

DOI： 10.18926/AMO/54819

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1515/jpem-2016-0258

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Genetic mutation of the coproporphyrinogen oxidase (CPOX) gene causes either hereditary coproporphyria (HCP) or harderoporphyria. HCP, a rare hepatic porphyria, causes acute attacks after puberty and rarely accompanies cutaneous symptoms. In contrast, harderoporphyria is an erythropoietic porphyria that represents photosensitivity and hemolytic anemia from the neonatal period. In patients with harderoporphyria, the p.Lys404Glu mutation is found in the homozygous or compound heterozygous state with another mutation, and a marked increase in harderoporphyrin is observed. This report describes a neonate with symptoms of erythropoietic harderoporphyria (photosensitivity of the skin, hemolytic anemia, and jaundice). However, the pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. We found a heterozygous, novel, four-base pair deletion in exon 7 of the CPOX gene, although other mutations including the p.Lys404Glu mutation in CPOX were not found. By unknown etiology, our patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development. Based on genetic mutation of the CPOX gene and information from a previous similar case report, we consider that neonatal-onset HCP is a variant of HCP.

DOI： 10.1007/8904_2017_20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

DOI： 10.1155/2017/2594231

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本小児循環器学会  

<p>背景：複雑先天性心疾患におけるFontan手術後に発症する蛋白漏出性胃腸症は発症すると難治・治療困難な病態であり生命予後を規定する．本研究の目的は当院でのPLE症例の予後と治療方針の検討である．</p><p>方法：1991～2014年に岡山大学病院でFontan手術後PLEの診断・治療を行った23例を対象にし，転帰の調査と死亡症例の傾向について検討を行った．</p><p>結果：Fontan手術施行401例中の23例（5.7％）に発症．フォローアップ期間は0.8～13年（中央値4.7年）．生存率は5年68％，10年54％．死亡原因は敗血症（2例），PLE増悪による多臓器不全（2例），心不全（1例），頭蓋内出血（1例）．死亡症例はPLE診断年齢が高くFontan手術から診断までの期間が長期であった．血行動態評価では治療前後の心係数（CI）と主心室駆出率（vEF），治療後の中心静脈圧（mCVP）に有意差を認めた．治療後CI＜2.8 L/min/mm, vEF＜50％，mCVP≧15 mmHgの症例は死亡率が高かった．</p><p>結論：PLEに対する治療は一定の有用性を認めたが，予後は満足できるものではない．血行動態的な治療の目標はCI，vEFの改善とCVPを低下させることと思われる．</p>

DOI： 10.9794/jspccs.33.202

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The urinary cross-linked N-terminal telopeptide of type I collagen (uNTx) levels in infantile osteogenesis imperfecta (OI) have not been well studied. Here we investigated the levels of uNTx in infants with OI and healthy infants. We collected spot urine samples from 30 infants with OI (male/female, 14/16; Sillence classification, I/II/III/IV: 15/3/6/6; age, 5.2±4.4 months) and 120 healthy infants (male/female, 75/45; age, 5.1±4.1 months) for the measurement of uNTx levels. The uNTx levels of the OI infants were significantly lower than those of the healthy infants (mean±SD, 1,363.7±530.1 vs. 2,622.2±1,202.6 nmol BCE/mmol Cr; p＜0.001). The uNTx levels of the infants with type I OI were significantly lower than those of the age-matched healthy infants, although an overlap was observed between the 2 groups. Among the 1-month-old infants, the uNTx levels of the infants with types I, III or IV OI were significantly lower than those of the healthy infants, without overlap (1,622.5±235.8 vs. 3,781.0±1,027.1 nmol BCE/mmol Cr; p＜0.001). These results indicate that uNTx levels are significantly lower in infants with OI than in healthy infants, and they suggest that uNTx might be useful as a reference for diagnosing OI.

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Estimation methods for pediatric weight have not been evaluated for Japanese children. This study aimed to assess the accuracy of mothers' reports of their children's weight in Japan. We also evaluated potential alternatives to the estimation of weight, including the Broselow tape (BT), Advanced Pediatric Life Support (APLS), and Park's formulae. We prospectively collected cross-sectional data on a convenience sample of 237 children aged less than 10 years who presented to a general pediatric outpatient clinic with their mothers. Each weight estimation method was evaluated using Bland- Altman plots and by calculating the proportion within 10% and 20% of the measured weight. Mothers' reports of weight were the most accurate method, with 94.9% within 10% of the measured weight, the lowest mean difference (0.27kg), and the shortest 95% limit of agreement (－1.4 to 1.9kg). The BT was the most reliable alternative, followed by APLS and Park's formulae. Mothers' reports of their children 's weight are more accurate than other weight estimation methods. When no report of a child's weight by the mother is available, BT is the best alternative. When an aged-based formula is the only option, the APLS formula is preferred.

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記述言語：英語  

DOI： 10.1016/j.resuscitation.2016.04.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is the most common cause of childhood-acquired heart disease in developed countries. However, the etiology of KD is not known. Aberrant immune responses are considered to play key roles in disease initiation and breastfeeding can mature immune system in infants. We thus examined the association between breastfeeding and the development of KD. METHODS: We used a nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 37 630 children who had data on their feeding during infancy. Infant feeding practice was queried at 6 to 7 months of age, and responses to questions about hospital admission for KD during the period from 6 to 30 months of age were used as outcome. We conducted logistic regression analyses controlling for child and maternal factors with formula feeding without colostrum as our reference group. RESULTS: A total of 232 hospital admissions were observed. Children who were breastfed exclusively or partially were less likely to be hospitalized for KD compared with those who were formula fed without colostrum; odds ratios for hospitalization were 0.26 (95% confidence interval: 0.12-0.55) for exclusive breastfeeding and 0.27 (95% confidence interval: 0.13-0.55) for partial breastfeeding. Although the risk reduction was not statistically significant, feeding colostrum only also provided a protective effect. CONCLUSIONS: We observed protective effects of breastfeeding on the development of KD during the period from 6 to 30 months of age in a nationwide, population-based, longitudinal survey in Japan, the country in which KD is most common.

DOI： 10.1542/peds.2015-3919

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Juvenile myelomonocytic leukemia (JMML) appears to be a life-threatening disease and showed poor prognosis even after hematopoietic stem cell transplantation (HSCT) because of high relapse rate. On the other hand, recent molecular analysis revealed the heterogeneity of JMML. Here we report that two JMML patients survived >20 years without HSCT and both patients had uniparental disomy of 11q23 where CBL is located without the phenomenon found in neither Noonan syndrome nor Noonan syndrome-like disorder. We think that some JMML patients with CBL mutation might show the good prognosis in later life after remission of JMML.

DOI： 10.1038/jhg.2016.8

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記述言語：英語  

DOI： 10.1016/j.jns.2016.03.038

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記述言語：英語  

DOI： 10.1002/ajmg.a.37557

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WALTER DE GRUYTER GMBH  

3-M syndrome (OMIM #273750, #612921, and #614205) is a rare autosomal recessive growth disorder that is characterized by pre- and postnatal growth retardation, normal intelligence, and characteristic faces. This syndrome also has characteristic radiological features, such as slender long bones and tall vertebral bodies. Three genes, cullin 7 (CUL7), coiled-coil domain containing 8, and obscurin-like 1 are genetic candidates of 3-M syndrome. Patients with 3-M syndrome have a characteristic facial appearance, including a triangular face, frontal bossing, an anteverted nose, dolichocephaly, and a long philtrum. However, information on adult 3-M syndrome patients, including facial appearance, is scarce. We report an adult female with 3-M syndrome that was caused by novel compound heterozygous mutations (c.4023-1 G>A in splice acceptor site of exon 22 and c.4359_4363dupGGCTG in exon 23) in the CUL7 gene. We also report the growth chart and changes in facial appearance of this patient from the neonate to adult.

DOI： 10.1515/jpem-2015-0272

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. We report the first detailed case of hypoparathyroidism complicated by biliary atresia. CASE PRESENTATION: A 1-year-old Japanese girl was admitted to our hospital for living donor liver transplantation. She suffered from obstructive jaundice owing to biliary atresia. She also had persistent hypocalcemia. Despite oral calcium and abundant vitamin D supplementation, a laboratory test showed hypocalcemia (1.4 mmol/l) and hyperphosphatemia (2.6 mmol/l). The intact parathyroid hormone level was normal (66 ng/l) with severe vitamin D deficiency (25-hydroxy vitamin D: undetectable levels). There were no rachitic changes in metaphysis on X-rays. Her family history showed that her mother had sensorineural deafness, a low serum calcium level (2.1 mmol/l), hypoplastic left kidney, and a past history of an operation for right vesicoureteral reflux. We suspected that this patient and her mother have hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. A heterozygous GATA3 gene mutation (c.736delGinsAT) was found in this patient and her mother, but not in her father. CONCLUSION: This familial case confirms the importance of family history in the diagnosis of HDR syndrome. Regardless of marked vitamin D deficiency, the complication of hypoparathyroidism prevented the onset of vitamin D deficiency rickets in our patient.

DOI： 10.1186/s12887-016-0550-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To compare the diagnostic performance of two norovirus rapid immunochromatographic kits (QuickNavi(®)-Norovirus [QN] and QuickNavi®-Norovirus 2 [QN2]; Denka Seiken, Niigata, Japan) for neonatal and infant faecal specimens. METHODS: Monthly faecal samples were collected from infants from birth to 12 months of age, and tested for norovirus using QN and QN2. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used as the gold standard for norovirus detection. The diagnostic performance of the kits was calculated. RESULTS: A total of 343 specimens from 81 infants were analysed. In all samples, the specificity of QN and QN2 was 80% (275/343) and 99% (339/343), respectively. In infants aged <1 month, the specificity of QN was 33% (23/70), increasing to 93% at 4 months of age. Specificity of QN2 was ≥94% in infants between 0 and 12 months of age. CONCLUSIONS: QN2 offers improved performance and is more useful than QN for the diagnosis of norovirus infection in the neonatal and infant period.

DOI： 10.1177/0300060515592902

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

DOI： 10.1186/s13054-015-0983-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Influence of hyperphenylalaninemia on lipoproteins in early life remains unclear. METHODS: We enrolled 24 phenylalanine hydroxylase (PAH)-deficient children who were classified into a phenylketonuria (PKU) group (n=12) lacking PAH activity and a benign hyperphenylalaninemia (HPA) group (n=12) having partial PAH activity, and their 11 non-affected siblings. We measured serum total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels together with apolipoproteins for the first year of life, and compared them with those of 30 age-matched healthy controls. RESULTS: The affected groups invariably had lower cholesterol levels than non-affected groups. At birth, HDL-cholesterol decrease was greatest and predominated over the LDL-cholesterol decrease: total cholesterol, 28/36% decrease to the control level in HPA/PKU; HDL-cholesterol, 33/51%; LDL-cholesterol, 20/28%. At 3months, the opposite changes were observed: total cholesterol, 16/28%; HDL-cholesterol, 13/23%; LDL-cholesterol, 16/33%. At 12months, LDL were still significantly lower in both groups (8/18%, p<.05 and .001), although HDL was significantly decreased only in the PKU group (15%, p<.05). Apolipoprotein A-I/A-II and B changed respectively in accordance with HDL-cholesterol and LDL-cholesterol changes. Despite similar phenylalanine levels, the PKU group invariably had lower cholesterol concentrations than the HPA group had. CONCLUSION: Irrespective of phenylalanine concentrations, lipoprotein synthesis in PAH-deficient children, particularly in PKU children, was suppressed in early life.

DOI： 10.1016/j.cca.2014.02.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

DOI： 10.1007/s13365-013-0231-5

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記述言語：日本語   出版者・発行元：(公社)日本新生児成育医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. METHODS: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. RESULTS: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. CONCLUSION: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.

DOI： 10.1111/ped.12139

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

DOI： 10.1111/ped.12094

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記述言語：日本語   出版者・発行元：岡山医学会  

DOI： 10.4044/joma.125.109

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その他リンク： http://ousar.lib.okayama-u.ac.jp/50817

記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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DOI： 10.1016/j.cca.2013.01.016

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その他リンク： http://orcid.org/0000-0002-4294-8030

DOI： 10.1016/j.cca.2012.10.011

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DOI： 10.1007/s10545-012-9514-x

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その他リンク： http://orcid.org/0000-0002-4294-8030

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. DESIGN: Prospective animal trial. SETTING: Research laboratory. SUBJECTS: Nine-week-old male C57BL/6 mice inoculated with H1N1. INTERVENTION: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days -1, 1, and 3. MEASUREMENTS AND MAIN RESULTS: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. CONCLUSIONS: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans.

DOI： 10.1097/CCM.0b013e3182676352

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study examined the clinical and biological importance of thioredoxin-1, a redox-active defensive protein that controls multiple biological functions, in pregnant women. We measured serum concentrations of thioredoxin-1, total hydroperoxides, and redox potential in 60 pregnant women at the early third trimester: gestational age of 27-29 weeks. The thioredoxin-1 concentration (mean ± SD) was 90 ± 42 ng/ml. Total hydroperoxides was 471 ± 105 U.CARR (1 U.CARR = 0.08 mg/dl H(2)O(2)). Redox potential was 2142 ± 273 µmol/l. The total hydroperoxides: redox potential ratio (oxidative stress index) was 0.23 ± 0.08. Thioredoxin-1, total hydroperoxides, and oxidative stress index were higher and redox potential was lower than in blood of healthy adults. Total hydroperoxides and redox potential were mutually correlated significantly and negatively. Thioredoxin-1 correlated significantly and negatively and redox potential correlated significantly and positively with body weight and body mass index. Thioredoxin-1 and redox potential correlated significantly and positively with uric acid and albumin, respectively. Thioredoxin-1 and oxidative stress index correlated significantly and negatively and redox potential significantly and positively with neonatal birth weight. These results suggest that high concentrations of thioredoxin-1 are linked to high oxidative stress status in pregnant women and that neonatal birth weight is affected by the maternal oxidative condition during later pregnancy.

DOI： 10.3164/jcbn.12-71

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記述言語：英語  

DOI： 10.1016/j.ymgme.2013.04.013

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DOI： 10.1016/j.ymgme.2012.08.004

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その他リンク： http://orcid.org/0000-0002-4294-8030

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, a pro-survival pathway, plays important roles in tumor cell growth. However, the role of Akt in the pathogenesis of pediatric B-precursor acute lymphoblastic leukemia (B-pre ALL) remains to be clarified. This study was undertaken to explore the clinical relevance and molecular mechanisms underlying the activation of Akt (i.e., phosphorylated Akt, P-Akt) in pediatric B-pre ALL. Procedure: We evaluated the activation status of Akt in bone marrow samples from 21 children with newly diagnosed B-pre ALL and correlated the expression level of P-Akt with clinicopathologic and prognostic features. Additionally, we transfected the myristoylated Akt cDNA into the B-pre ALL cell line, Nalm-6, and examined the effect, in vitro, of Akt activation on the response to antitumor drugs. Results: P-Akt expression in B-pre ALL blast cells at diagnosis was associated significantly with poor response to induction chemotherapy including prednisolone, dexamethasone, vincristine, and adriamycin in B-pre ALL patients. Both overall survival and relapse-free survival in patients with P-Akt expression were reduced significantly more than in patients without P-Akt expression. Activation of Akt reduced the extent of apoptosis induced by the antitumor drugs in Nalm-6 listed above. Activation of Akt did not induce expression of P-glycoprotein, a drug transporter that is capable of conferring multidrug resistance. Conclusion: These results support the contention that Akt activation is a mechanism of chemotherapeutic resistance in B-pre ALL and suggest that Akt can be a therapeutic target for the treatment of relapsed or refractory pediatric B-pre ALL. © 2011 Wiley Periodicals, Inc.

DOI： 10.1002/pbc.24034

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer-Verlag Berlin Heidelberg  

A large body of circumstantial evidence emphasizes the critical role of reactive oxygen species (ROS), including superoxide anion and nitric oxide (NO), in acute and chronic pediatric diseases. About 15 years ago, measurement of oxidative damage affecting tissues and organs using specific biomarkers was introduced into the field of pediatric medicine. This chapter is intended to describe recent progress in clinical application of oxidative stress biomarkers in pediatric medicine. First, this chapter briefly presents the biochemistry and pathophysiology of ROS and antioxidative defense systems. Second, it discusses the interrelationship of endothelial dysfunction, NO system blockade, and oxidative stress. Third, it presents a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. The discussion emphasizes that many good biomarkers are readily measurable using enzyme-linked immunosorbent assay. Fourth, this chapter presents age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2′-deoxyguanosine, nitrite/nitrate, and pentosidine. Furthermore, our new and interesting data related to oxidative stress and antioxidative defenses in congenital metabolic disorders, such as Wilson disease, urea cycle defects, citrin deficiency, and phenylketonuria, are presented. Rapid diagnostic tests for measuring blood levels of total hydroperoxides and biological antioxidative potential and urinary levels of 8-hydroxy-2′-deoxyguanosine are also explained. Finally, this chapter describes recent clinical studies that have evaluated the efficacy of antioxidative intervention for oxidative-stress-related diseases. Repeated measurement of multiple appropriate parameters will enable us to discern the pathophysiological patterns of pediatric diseases and guide our therapies appropriately.

DOI： 10.1007/978-3-642-30018-9_36

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DOI： 10.1016/j.braindev.2011.11.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The mechanism underlying the development of osteopenia or osteoporosis in longstanding phenylketonuria (PKU) remains to be clarified. We investigated the details of bone metabolism in 21 female and 13 male classical PKU patients aged 20-35 years. Vitamin D (VD), parathyroid hormone (PTH), bone turnover markers, and daily nutrient intake were examined. The patients had lower daily energy and protein intake than did the age-matched controls (22 women, 14 men), but their respective fat, VD, and calcium intake did not differ. Serum 1,25-dihydroxy VD and 25-hydroxy VD levels in female and male patient groups were significantly higher and lower than those in respective control groups (females, P &lt; 0.001; males, P &lt; 0.05 and P &lt; 0.01, respectively). Serum intact PTH levels were significantly higher in the female patient group (P &lt; 0.05). Urinary calcium levels in the patient groups were significantly higher than those of the control subjects (females, P &lt; 0.001; males, P &lt; 0.05). Bone resorption markers were significantly higher in patients than in controls, although bone formation markers were not different. Patient serum levels of osteoprotegerin-inhibiting bone resorption were significantly lower (females, P &lt; 0.001; males, P &lt; 0.01). None of the bone parameters correlated significantly with serum phenylalanine or nutrient intake. PKU patients exhibited lower VD status and more rapid bone resorption despite normal calcium-VD intakes.

DOI： 10.1007/s00774-011-0276-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Few studies have looked at optimal or acceptable serum phenylalanine levels in later life in patients with phenylketonuria (PKU). This study examined the oxidative stress status of adolescents and adults with PKU. Forty PKU patients aged over fifteen years were enrolled, and were compared with thirty age-matched controls. Oxidative stress markers, anti-oxidant enzyme activities in erythrocytes, and blood anti-oxidant levels were examined. Nitric oxide (NO) production was also examined as a measure of oxidative stress. Plasma thiobarbituric acid reactive species and serum malondialdehyde-modified LDL levels were significantly higher in PKU patients than control subjects, and correlated significantly with serum phenylalanine level (P&lt;0.01). Plasma total anti-oxidant reactivity levels were significantly lower in the patient group, and correlated negatively with phenylalanine level (P&lt;0.001). Erythrocyte superoxide dismutase and catalase activities were higher and correlated significantly with phenylalanine level (P&lt;0.01). Glutathione peroxidase activity was lower and correlated negatively with phenylalanine level (P&lt;0.001). The oxidative stress score calculated from these six parameters was significantly higher in patients with serum phenylalanine of 700-800 mu mol/l. Plasma anti-oxidant substances, beta-carotene, and coenzyme Q(10) were also lower (P&lt;0.001), although the decreases did not correlate significantly with the phenylalanine level. Serum nitrite/nitrate levels, as stable NO products, were higher together with low serum asymmetric dimethylarginine, as an endogenous NO inhibitor. Oxidative stress status is closely linked with serum phenylalanine levels. Phenylalanine level in should be maintained PKU below 700-800 mu mol/l even in adult patients. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ymgme.2011.03.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.metabol.2010.08.008

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記述言語：日本語   出版者・発行元：(株)総合医学社  

無疱性帯状疱疹は皮疹を欠く無疱性の水痘帯状疱疹ウイルス(VZV)感染症であるが、その診断は困難であることが少なくない。今回、急性リンパ性白血病(ALL)の寛解期維持療法中にVZV再活性化により無疱性帯状疱疹と髄膜炎を発症した小児例を経験した。症例は15歳男児で、B前駆細胞性ALLの維持療法中に発熱、嘔吐を来して入院した。経過中、脳脊髄液細胞増加と左末梢性顔面神経麻痺が出現した。皮疹は出現しなかったが、髄液と唾液よりVZV-DNAが検出されたため、VZV再活性化による無疱性帯状疱疹および髄膜炎と診断した。プレドニゾロンとアシクロビルの併用により、諸症状は改善した。白血病の経過中に生じる顔面神経麻痺は、原病の再発と関連する場合が多いが、ウイルスの再活性化に伴う場合もあり、その鑑別診断は適切な治療を行ううえで重要である。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00643&link_issn=&doc_id=20110603230013&doc_link_id=%2Fag1snrsd%2F2011%2F006406%2F013%2F1111-1115%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2011%2F006406%2F013%2F1111-1115%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

DOI： 10.1016/j.braindev.2011.01.009

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DOI： 10.1016/j.annemergmed.2009.06.506

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記述言語：日本語   出版者・発行元：(一社)日本小児感染症学会  

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記述言語：日本語   出版者・発行元：THE JAPANESE SOCIETY OF PEDIATRIC ALLERGY AND CLINICAL IMMUNOLOGY  

一酸化窒素 (NO) はNO合成酵素の働きにより L-arginine を基質として生合成されるフリーラジカルである. 呼吸器系を構成するほぼすべての細胞がNOを産生することから, NOは生理的にも様々な呼吸器疾患においても重要な役割を果たすと考えられる.<br>著者らは, 以前より血管内皮の病態生理について臨床的および実験的研究を推進してきた. 本論文では, それらの研究成果に基づいて血管内皮, NOを軸とした呼吸器系の病態生理について論じる.<br>肺の血管内皮は肺血流や換気血流均衡を調節することで血液の効率的な酸素化に寄与している. また, 血管内皮は気道―血管関門を構築し白血球の接着浸潤を抑制することで気道のホメオスターシスを維持している. ところが, 気管支喘息などの炎症性肺疾患では誘導合成されたNOは活性酸素種と相互作用し組織障害性の強い活性窒素種に変化する. このような酸化ストレスが亢進すると血管内皮機能は低下し, 肺の組織障害はさらに進展する. こうしたパラダイムに基づいて, 近年NOが創薬ターゲットとして注目されている. NOガス吸入療法はその代表である.

DOI： 10.3388/jspaci.16.475

CiNii Article

CiNii Books

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING ASIA  

Background : Almost all newborns have phimosis, which is known as one of the risk factors for urinary infection. The present study analyzed which specific prepuce conditions correlated with the development of febrile urinary infection in Japanese male infants.
Methods : The subjects consisted of 100 children, 64 boys and 36 girls, with febrile urinary infection. Prepuces were classified by their retractability in the male patients and in 714 healthy boys.
Results : Ninety-four percent of first febrile urinary infections occurred before 7 months of age in boys, whereas only 37% of the girls had first infections by that age. The prepuce covered the external urethral meatus in 96% of the healthy boys aged 3 years or less. A gentle retraction maneuver could not uncover the urethral meatus in approximately 40% of the boys aged 0 6 months. The frequency started to decline spontaneously after that age. Male patients aged 0 6 months significantly more often had tightly covered meatus than did healthy neonates (85% vs 42%, P&lt;0.0001).
Conclusions : These findings indicate that it is specifically those boys whose external urethral meatus are tightly covered with foreskin who constitute the high-risk group for urinary infection. Awareness of this observation should help with diagnosing and managing urinary infection in young boys.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Aim: The purpose of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence and course of focal segmental glomerulosclerosis (FSGS) in our pediatric population. Methods: Genotypes for MTHFR were determined in 15 primary FSGS patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by the polymerase chain reaction and restriction fragment length polymorphism method. Results: For the whole group, the genotype frequencies (CC/CT/TT) of MTHFR in FSGS and control subjects were almost comparable. The TT genotype was associated with early onset of the disease as compared with the CC genotype. Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and developed into end-stage renal failure, while those carrying either CC or CT genotype did not. Conclusion: We speculate that the TT genotype may be associated with early development and progression of childhood FSGS. Confirmatory studies using larger and ethnically distinct populations are needed to reveal the role of homocysteine in FSGS with consideration of medical interventions. Copyright (C) 2002 S Karger AG, Basel.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The purpose of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence and course of focal segmental glomerulosclerosis (FSGS) in our pediatric population. METHODS: Genotypes for MTHFR were determined in 15 primary FSGS patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: For the whole group, the genotype frequencies (CC/CT/TT) of MTHFR in FSGS and control subjects were almost comparable. The TT genotype was associated with early onset of the disease as compared with the CC genotype. Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and developed into end-stage renal failure, while those carrying either CC or CT genotype did not. CONCLUSION: We speculate that the TT genotype may be associated with early development and progression of childhood FSGS. Confirmatory studies using larger and ethnically distinct populations are needed to reveal the role of homocysteine in FSGS with consideration of medical interventions.

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING ASIA  

Background : For ambulatory pediatric outpatients, reports of abnormalities of bone metabolism associated with anti-epileptic drugs are inconsistent and may be difficult to interpret.
Methods : The effects of long-term anti-epileptic therapy (mainly valproic acid and/or carbamazepine) on bone mineral status were evaluated in ambulatory epileptic patients (seven males and 11 females) aged 5.5-15.9 years. Bone mineral density (BMD) at the lumbar spine was measured by dual-energy X-ray absorptiometry and markers of bone and mineral metabolism were determined.
Results : The mean BMD was decreased by 9% in our patients relative to the control, and five patients (all males) showed osteopenia, defined as BMD SD scores less than - 1.5. Serum levels of minerals, intact parathyroid hormone and 1alpha,25 (OH)(2) vitamin D were within the normal ranges. In most patients, serum levels of intact osteocalcin, carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked telopeptide of type I collagen were reduced relative to the corresponding mean control values. The BB genotype by Bsm I restriction fragment length polymorphism, associated with low BMD, was not found in our patients. The dietary calcium intake in the osteopenic patients was significantly lower than that of the non-osteopenic patients.
Conclusions : Our results indicate that long-term anti-epileptic treatment induces a state of decreased bone turnover in children, resulting in osteopenia preferentially in males. The alterations may be due, at least in part, to direct effects of the drugs on bone cells; and that low calcium intake could be an aggravating factor for anti-epileptic-associated osteopenia.

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記述言語：日本語   出版者・発行元：(一社)日本小児腎臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児腎臓病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING INC  

Background. Congenital solitary kidneys, which are susceptible to renal failure, have been considered mostly due to unilateral renal agenesis and partly due to renal aplasia. Risk of familial recurrence and of other associated anomalies is known to be much higher in renal agenesis than in renal aplasia. However, differential diagnosis between the two renal anomalies is difficult, and renal agenesis has been found much less frequently in ultrasound screening studies of fetuses than in autopsy studies.
Methods. In order to investigate the nature and incidence of the congenital solitary kidney, the present study performed ultrasound screening of the kidneys in 4000 newborn babies. A diagnosis of renal agenesis was made when ultrasound identified no renal parenchyma and renoscintigraphy showed no renal function, and renal aplasia when there was a renal parenchyma without any function.
Results. Primary screening detected 52 babies suspected of having small kidneys and one baby with a multicystic dysplastic kidney, but no baby with renal agenesis. Forty-seven of the 53 babies underwent a second ultrasound scanning at one month of age. Three small kidneys in three babies further decreased in size, had no function and were diagnosed as renal aplasia (which has an incidence rate of one in 1300). Follow-up ultrasound studies showed further regression in all three, which became very hard to distinguish by one year of age.
Conclusions. The present study showed that ultrasound in the neonatal period could identify the aplastic kidney, which had a reniform shape, not rudimentary, during the newborn period, and regressed rapidly thereafter. These findings indicate that most renal agenesis diagnosed clinically thus far might more correctly be renal aplasia.

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記述言語：日本語   出版者・発行元：(一社)日本小児アレルギー学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

We report here an examination of the effect of thioredoxin (TRX) on the secretion of growth hormone (GH) from rat anterior pituitary cells in vitro. Treatment of rat pituitary cells with growth hormone-releasing factor (GRF), but not GH, led to a significant increase in intracellular TRX protein levels. GRF, recombinant human TRX (rhTRX), and a combination thereof were all shown to induce immediate GH secretion from pituitary cells, as evidenced by perifusion experiments. RhTRX, but not other reducing agents such as beta -mercaptoethanol and N-acetyl-L-cysteine, augmented GRF-stimulated and -unstimulated GH secretion from rat pituitary cells in a dose-dependent manner. RhTRX did not significantly affect the GH mRNA expression of pituitary cells stimulated in the presence or absence of GRF. In addition, rhTRX-augmented GH secretion was not significantly affected by the presence of cycloheximide. Collectively, these findings suggest that TRX is induced by stimulation with GRF and plays a regulatory role in GH secretion from rat anterior pituitary cells by enhancing the secretion of stored GH, rather than by the synthesis of GH.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background, There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). Methods: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 (SD) 5.0 years. Results: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p &lt; 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. Conclusion: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes. Copyright (C) 2001 S. Karger AG, Basel.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING ASIA  

Background: Uroguanylin is a novel natriuretic and diuretic peptide originally isolated from urine.
Methods: To determine whether uroguanylin has a physiologic role during the perinatal period, uroguanylin levels in umbilical cord plasma obtained at the time of delivery were measured by radioimmunoassay and compared with cord serum osmolality.
Results: Mean (+/-SD) cord plasma uroguanylin concentrations (8.8+/-2.1 fmol/mL) were higher compared with normal adult values. The extent of maturity, mode of delivery and gender did not appear to influence cord uroguanylin levels. The uroguanylin concentration had a significant positive correlation with cord serum osmolality.
Conclusion: These findings support some regulatory role of this peptide in perinatal renal and cardiovascular adaptation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Atopic dermatitis (AD) is a chronic inflammatory skin disease of unknown etiology. To examine the involvement of impaired homeostasis of oxygen/nitrogen radicals in childhood AD, we compared the levels of urinary 8-hydroxy-2'-deoxyguanosine (marker of oxidative stress), nitrite/nitrate (marker of nitric oxide synthesis) and selenium (marker of selenium store) in 27 children with AD to those of 25 healthy control children. Urinary 8-hydroxy-2'-deoxyguanosine was significantly higher and nitrite/nitrate levels were significantly lower in patients with AD than in the control. Urinary selenium levels were similar in both groups. Our findings suggest that impaired homeostasis of oxygen/nitrogen radicals and increased oxidative stress are involved in the pathophysiology of childhood AD, and indicate that suppression of oxidative stress might be a potentially useful strategy for the treatment of AD. (C) 2001 Elsevier Science Inc. All rights reserved.

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記述言語：日本語   出版者・発行元：(一社)日本小児腎臓病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE INC  

Background. It has been recently found that mice, especially males, with a disrupted angiotensin type 2 receptor (AT2R) gene, which is located on the X-chromosome, often have a range of congenital anomalies of the kidney and urinary tract (CAKUT), including renal hypoplasia, and that Caucasian male patients with ureteropelvic junction stenosis (UPJ) and multicystic dysplastic kidneys frequently have A-G transition in intron 1 of the AT2R gene. We have previously found that renal hypoplasia is remarkably predominant in Japanese boys.
Methods. We investigated sex ratios for the frequency of each CAKUT. The frequency of the A-G transition between the controls and 66 Japanese boys with CAKUT were compared. There was renal hypoplasia in 16, UPJ in 17, vesicoureteral in 20, and other anomalies in 13. We also investigated whether any mutations in A T2R genes were detectable in patients with renal hypoplasia.
Results. In contrast to mice with a disruption of the AT2R gene, the male-to-female ratios in human patients proved to be considerably variable: 16 for renal hypoplasia, 2.1 for UPJ, 0.8 for vesicoureteral, and 1.2 for others. The frequency of the A-G transition was not different between the control population and the patients with CAKUT [31 of 102 (30%) vs. 23 of 66 (35%), respectively]. A sequencing study disclosed no mutations in nine boys with renal hypoplasia.
Conclusions. These findings indicate that the AT2R gene may not play a major role in the development of renal hypoplasia and other CAKUT in humans, at least in the Japanese population.

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

症例は妊娠31週に帝王切開にて出生した女児で,生下時より胸部X線上全肺野び漫性の泡沫状陰影を認め,呼吸不全を呈しており,特徴的なX線像と高IgM血症の存在から重症型のWilson-Mikity症候群と診断された.集学的治療を施行したが,患児は生後62日目に多臓器不全にて死亡した.間質性肺炎の活動性の特異マーカーであるKL-6とサーファクタント蛋白質Dの血中濃度の測定結果では前者のみが異常高値を示した.この結果は慢性炎症の継続により,患児の肺の線維化が著しく高度になっていたことを示唆するものと考えられた

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

Objective: This study was to examine the relationship between gastric acid suppression and healing of peptic ulcers in children. Materials and Methods: Twenty-seven patients (6-14 years old) with peptic ulcers confirmed by gastroscopy were randomized to receive ranitidine (n=16) and omeprazole (n=11) for five weeks. Intragastric 24hour pH monitoring was performed before treatment and repeated three times during the treatment: day one, week one, and week five. Endoscopy was repeated after five weeks of treatment. Results: All patients in the omeprazole group were healed, as were 10 of the 16 patients (63%) in the ranitidine group. The maximal suppression of gastric acidity by omeprazole appeared during the first week and continued for four weeks. For the ranitidine group, the gastric pH and duration with gastric pH > 3 remained almost stable in the healed patients, while the gastric acid suppressive effect attenuated significantly and disappeared at the end of the treatment in the unhealed patients. The Helicobacter pylori status after eradicative treatment was comparable between the healed and unhealed patients. Conclusion: These findings indicate that a higher degree and a longer duration of gastric acid suppression are beneficial for healing of peptic ulcers in children.

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記述言語：日本語   出版者・発行元：(一社)日本小児アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児アレルギー学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Background A long course of the initial prednisolone therapy has been shown to be more effective than standard-course therapy in reducing relapse rates in children with idiopathic nephrotic syndrome, but it is commonly accompanied by corticosteroid toxicities. There has been no study on prednisolone dosage for the effective treatment of nephrotic syndrome.
Methods. Sixty-eight children (42 boys and 26 girls) with an initial attack of nephrotic syndrome were randomly allocated into two different long-course treatment groups. Patients in Group 1 received a daily prednisolone dose of 60 mg/m(2) for six weeks, followed by an alternate-day dose of 40 mg/m(2) for six weeks. Patients in Group 2 had a daily dose of 40 mg/m(2) instead of 60 mg/m(2).
Results. Four children in each group did not respond within six weeks. Group 1 was associated with a significantly earlier response but more frequent corticosteroid toxicities than Group 2. Boys in Group 1 had a higher rate of sustained remission than boys in Group 2 (P = 0.0073), especially boys four years old or more (P = 0.0027), but girls did not show a significant difference (P = 0.863). Boys four years old or more in Group 1 had a course of frequent relapsing less often than those in Group 2 (2 of 13 vs. 6 of 8, P = 0.0075).
Conclusion. These findings indicate that efficient prednisolone doses may vary between sexes and ages, and that a higher initial prednisolone therapy may be of greater benefit to older boys.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG  

Seven patients who had an initial attack of nephrotic syndrome in childhood and had frequent relapses even after cyclophosphamide therapy were given a 2-year course of azathioprine. The mean annual relapse rates decreased from 2.4 +/- 0.5 in the year preceding azathioprine to 0.4 +/- 0.8 in the 1st and 2nd years after its initiation. All six patients who were observed for more than 6 months after discontinuation of the therapy were relapse free for this period. Average doses of prednisolone could also be decreased in the 2nd and subsequent years after the therapy. There were no significant toxic effects. Long-term azathioprine therapy may be well tolerated and effective for nephrotic patients with frequent relapses.

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記述言語：日本語   出版者・発行元：日本小児腎不全学会  

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記述言語：日本語   出版者・発行元：日本小児呼吸器疾患学会  

DOI： 10.5701/jjpp.11.55

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE ASIA  

Background: A genetic aberration in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (677 C to T substitution) has been shown to result in reduced enzyme activity. The hypothesis tested in the present study was that a higher proportion of Kawasaki disease (KD) patients with coronary artery lesions (CAL) would have the T677 allele compared with patients without CAL and healthy subjects.
Methods: Genotypes for MTHFR were determined in 75 KD patients (male : female ratio 52:23) and 238 healthy subjects (male : female ratio, 110:128) by the polymerase chain reaction and restriction fragment length polymorphism method.
Results: The results indicated that female KD patients had a significantly higher frequency of the TT genotype compared with female control subjects. In the female population, the frequency of the TT genotype in patients with initial coronary aneurysm was significantly lower than in patients without this manifestation. Analysis of the data for the male population showed that the frequency of the TT genotype in KD patients developing coronary stenosis, occlusion or myocardial infarction was higher than that in those without these manifestations, although the difference was statistically insignificant.
Conclusions: The TT genotype may protect female KD patients against initial aneurysm formation and predispose male KD patients to severe coronary complications. Further large-scale studies may be required to confirm the contribution of homocysteine in the coronary sequelae of KD.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis. Copyright (C) 2000 S. Karger AG, Basel.

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W S MANEY & SONS LTD  

To examine the involvement of reactive oxygen species, we measured the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative stress, in cerebrospinal fluid samples from 63 children with and without meningitis. We observed that the mean concentration of 8-OHdG in samples obtained during the early phase of bacterial meningitis, but not aseptic meningitis, was significantly higher than that in control samples. Clinical and laboratory improvement was associated with a fall in the 8-OHdG concentration in the patients with bacterial meningitis. Our findings suggest the presence of enhanced oxidative stress in the central nervous system of children with bacterial meningitis.

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記述言語：日本語   出版者・発行元：THE JAPANESE SOCIETY OF PEDIATRIC ALLERGY AND CLINICAL IMMUNOLOGY  

DOI： 10.3388/jspaci.14.351

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

We conducted a comparative study to evaluate whether early (4-7 days of age) tow-dose dexamethasone (DEX) therapy in preterm infa nts with surfactant-pretreated respiratory distress syndrome (RDS) would facilitate extubation and improve the clinical outcome. Twenty-six preterm infants with surfactant-pretreated RDS who were oxygen- and ventilator-dependent at 4 days of postnatal age were enrolled. Twelve infants were in the historical comparison group, and 14 infants were assigned to receive DEX 0.125 mg/kg i.v., every 12 h, for a total of 6 doses. At study entry, the two groups had a comparable clinical status. DEX therapy significantly facilitated weaning from mechanical ventilation (median interval, 6 vs. 24 days, p &lt; 0.005) and shortened duration of oxygen supplementation (9 vs. 28 days, p &lt; 0.05) as compared with the historical comparison group. At 28 days of age, the occurrence of chronic lung disease (CLD) was significantly lower (1/14 vs. 6/12, p &lt; 0.05) and there was a significant decrease in the incidence of ventilator dependence (0/14 vs. 5/12, p &lt; 0.05) in the DEX group. DEX therapy did not influence the incidence of significant complications such as infection, periventricular leukomalacia or retinopathy of prematurity. We conclude that in a selected high-risk group of preterm infants, early low-dose DEX treatment results in improvement in pulmonary outcome without significant side effects.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE ASIA  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE INC  

Background The neonatal period has been characterized as a time when males have a much higher incidence of urinary infection and severe ureteral reflux than females. However, little information about the voiding function in the neonatal period is available.
Methods. The bladder urine volumes, before and after voiding, and urinary how rates were determined with the use of noninvasive voiding-provocation maneuvers and ultrasound in the apparently normal neonates.
Results. There was no significant difference in the prevoid bladder urine volume between the two sexes. After they were stimulated to enhance the tension of their abdominal wall musculature, 65 of 118 females (55.1%) and 64 of 115 males (55.7%) voided. The voiding was observed in 94 (81.0%) of the 116 neonates who had had a prevoid volume above 12 ml. The residual urine expressed as a percentage of the prevoid volume was significantly higher in the males (median, 12.0% in males vs. 3.0% in females, P &lt; 0.01), with the values being above 20% in 26 (41%) of the 64 males compared with 10 (15%) of the 65 females (P &lt; 0.01). Urinary flow rates, determined in 52 neonates, were significantly smaller in males than in females (mean +/- so, 2.6 +/- 0.9 g/second vs. 3.8 +/- 1.3 g/second, respectively, P &lt; 0.001).
Conclusion. This voiding function study with ultrasound using noninvasive voiding-provocation maneuvers successfully revealed that male neonates have a larger residual urine volume and smaller urinary flow rates than female neonates. This study should be useful for the diagnosis of voiding dysfunction in children with abnormal urinary symptoms.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

We measured urinary excretion of collagen crosslinks, pyridinoline and deoxypyridinoline, in term and preterm newborns at birth and evaluated the developmental changes in bone turnover. Collagen crosslink excretion in newborns was more than 10 times higher than reported adult values and several times higher than those of older children. The values were significantly higher in preterm newborns than in term newborns. In addition, a significant and inverse correlation was found between urinary collagen crosslinks and gestational age in preterm newborns. Excretion of crosslinks during this period did not correlate with beta,microglobulin, suggesting that the excretion was not directly influenced by renal function in newborns. We conclude that bone turnover assessed by measurement of collagen crosslink excretion is high at birth and that preterm newborns have higher bone turnover than term newborns. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Inc.  

Background. Vesicoureteral reflux (VUR) is assumed to be congenital, and its early diagnosis is desired in order to prevent acquired renal damage. However, the incidence of VUR in neonates remains to be revealed. Methods. Two thousand newborn babies (1048 boys and 952 girls) underwent voiding ultrasonography (an ultrasound examination of urinary tract during provoked voiding). Those who showed transient renal pelvic dilation during voiding, who had small kidneys, or who subsequently developed urinary infection underwent voiding cystourethrography. Results. Transient renal pelvic dilation was observed in 16 babies (0.8%), including one boy with small kidneys. Among the rest of the babies, one boy had a small kidney, and nine babies subsequently developed urinary infection. Voiding cystourethrography revealed VUR in 24 ureters of 16 children (11 boys and 5 girls). Dimercaptosuccinate renoscintigraphy confirmed small kidneys, with generally reduced tracer uptake in a total of three boys, all having VUR. Voiding ultrasonography detected transient renal pelvic dilation in 17 (71%) of the 24 kidneys with VUR and, strikingly, 16 of the 17 (94%) kidneys with high- grade VUR (grade III or more). Conclusion. This study effectively detected VUR in 0.8% of the neonates (mostly of high grades and predominantly in males) and voiding ultrasonography showed a decided usefulness for the detection of VUR. The male preponderance of VUR in neonates was considered to be due to the occurrence of congenitally small kidneys, with reflux found exclusively in males and easier ultrasound detection of VUR in male neonates because the majority of diagnoses are reported to be high grades of VUR.

DOI： 10.1046/j.1523-1755.1999.00380.x

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記述言語：日本語   出版者・発行元：The Japanese Society for Pediatric Nephrology  

新生児・未熟児医療の進歩により病的新生児の救命率が著しく向上している。それに伴って，生来的に未熟な新生児腎臓もまた周生期疾患の標的臓器の1つとして注目されている。本稿では，これまであまり着目されていなかった新生児の尿中マーカーの解釈と臨床応用について論じた。すなわち，新生児期を早期と後期に分割し，それぞれの時期で臨床的意義の高いマーカーを列挙し，概説した。実地臨床の場で尿中マーカーを十分に活用することができれば，病的新生児の腎機能あるいは栄養・代謝状態を的確に評価することが可能になる。病的新生児に対するless invasive careとintact survivalの向上の観点から，小児科医のこの方面への関心が深まることが期待される。

DOI： 10.3165/jjpn.12.79

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その他リンク： http://search.jamas.or.jp/link/ui/1999215064

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney. Copyright (C) 1998 by W.B. Saunders Company.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel of the renal collecting duct and is excreted in human urine. We measured the urinary excretion of AQP-2 by radioimmunoassay in 14 term and 12 preterm infants aged 1 month. Excretion of AQP-2 was low compared with adults, and correlated significantly with urine osmolality in preterm infants. Our results demonstrate that AQP-2 water channels are expressed in the renal collecting duct of both term and preterm infants. (C) 1998 Elsevier Science Ireland Ltd.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO  

Osteopenia is a frequent condition in preterm infants, but its pathogenesis is uncertain. In the present study, we measured longitudinal changes in the excretion of pyridinium cross-links of collagen (specific markers of bone resorption) and evaluated the relationship between collagen cross-links and other indexes of bone and renal function in preterm infants. In these infants, urinary collagen cross-links were markedly increased on day 7 and day 30 of life and at estimated full-term gestation. The values were several times higher than those of older children and almost comparable to those of healthy full-term infants. Cross-link excretion did not correlate with beta(2)-microglobulin (B2M) or N-acetyl-beta-D-glucosaminidase (NAG) activity (markers of renal function), indicating that cross-link excretion is not influenced directly by infantile renal function. High serum osteocalcin and low bone mineral density (BMD) in the lumbar spine were also observed at estimated full-term gestation, There was no significant correlation between collagen cross-link excretion and either serum osteocalcin or spine BMD. We conclude that a state of high bone turnover underlies the development of osteopenia in preterm infants. Copyright (C) 1998 by W.B. Saunders Company.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SCANDINAVIAN UNIVERSITY PRESS  

To investigate the involvement of nitric oxide (NO) in childhood meningitis, we measured the concentrations of NO2- (a stable metabolite of NO) in serial samples of cerebrospinal fluid (CSF) from :II children with septic and 7 with aseptic meningitis and 26 control patients without meningitis. The mean concentration of NO2- in samples obtained during the early stages of septic meningitis, but not aseptic meningitis, was significantly higher than in control samples. Clinical and laboratory improvement following administration of antibiotics and dexamethasone was associated with a fall in CSF [NO2-] to normal levels in these patients. CSF [NO2-] remained almost consistently within the normal range in patients with aseptic meningitis. Our findings indicate that NO production is enhanced in the CSF compartment of children with septic meningitis and support the hypothesis that NO is involved in the pathophysiology of septic meningitis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Allergology  

To analyze the development of antigen-specific IgE in infants and its clinical usefulness, the levels of IgE antibodies against egg white (f1) and cows' milk (f2) in 33 sera from cord blood, 118 sera from atopic dermatitis (AD) infants and 197 sera from non-atopic control infants were measured by using the CAP radioallergosorbent test (RAST) fluoro enzyme immunoassay (FEIA) system, which has a detection limit of 0.15 Ua/mL for fl and 0.20 Ua/mL for f2. No antigen-specific IgE was detected in cord blood, whereas in infants younger than 6 months of age, 38.5% of AD infants and 6.6% of the non-atopic controls showed IgE against f1 (≤0.70 Ua/mL) and 14.3 and 4.0%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. When the cut- off point for positive versus negative f1 RAST was set at 0.15 or 0.35 Ua/mL instead of 0.70 Ua/mL, the significance of the difference in f1 RAST- positive and -negative proportions between atopic and non-atopic infants did not change. Repeated examination of f1 RAST revealed later positive conversion in the majority of AD patients, with no detectable or very low levels (0.15-0.35 Ua/mL) of f1 -specific IgE. In infants at 6 months of age or older, 44.4 and 12.0% of AD patients and non-atopic controls, respectively, showed IgE against f1 (≤ 0.70 Ua/mL) and 37.1 and 22.6%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. These results suggest that f1 RAST at a concentration of 0.15 Ua/mL or higher has diagnostic value for egg allergy in AD infants, especially in infants younger than 6 months of age. The f1 RAST should be examined repeatedly in AD infants with low levels of IgE against f1. Similar results were obtained for f2- specific IgE, but there was a significant decrease in the specificity when the cut-off point was set at 0.20 Ua/mL.

DOI： 10.2332/allergolint.47.129

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記述言語：日本語   出版者・発行元：The Japanese Society for Pediatric Nephrology  

特発性膜性腎症 (IMN) に対しては，副腎皮質ステロイド剤や免疫抑制剤などが治療に用いられることが多いが，その評価に関しては統一的な見解はいまだない。本稿では，わが国の小児におけるIMN症例の臨床経過および治療の現況とそれらの特徴を集約してとらえ，諸外国の症例と対比させながら，日本人小児のIMNに対する管理方針について論じた。<br> 成人例よりも自然寛解率が高く，とくに欧米の患児よりも予後の良好な日本人小児のIMNの治療指針としては，現段階では次のように考えるのが妥当であろう。すなわち，ネフローゼ症候群を呈さない症例の場合は，一過性の可能性が高く，腎機能障害を残す危険性もきわめて低いので，ステロイドあるいは免疫抑制剤の治療を要しない。すなわち，対症療法のみを行う。ネフローゼ状態がある期間続く場合には，腎機能障害を呈する危険もありうるので，あるいは，ネフローゼ症候群そのものによる合併症を抑止する目的で，ステロイド剤を試みてもよい。また，免疫抑制剤については，日本人小児には原則として使用すべきではないと思われる。

DOI： 10.3165/jjpn.11.203

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その他リンク： http://search.jamas.or.jp/link/ui/1999096910

記述言語：日本語   出版者・発行元：The Japanese Society for Pediatric Nephrology  

一酸化窒素 (NO) は多彩な生理活性を有するガス状ラジカルであり，ここ10年の間きわめて精力的な研究が展開されてきた。われわれは，小児におけるNOの生理学的・病態学的意義を明らかにするために，尿中の一酸化窒素代謝物濃度を指標として以下の臨床的研究を行ったので，その成果を紹介する。(1)正常小児における内因性NO産生の評価，(2)川崎病，気管支喘息の患者におけるNO産生の評価，(3)インスリン，L-アルギニンのNO合成系への作用に関する研究がその内容である。小児の病態生理においてNOがいかなる役割を果たしているのか不明のところが多く，今後の研究が期待される。

DOI： 10.3165/jjpn.11.79

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その他リンク： http://search.jamas.or.jp/link/ui/1998196311

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

We measured the urinary nitrite and nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm newborns on the ist and 4th days of age. In the infants of both groups, the urinary NOx- excretion significantly increased from the ist to the 4th day. The urinary NOx- excretion in preterm infants was significantly higher as compared with term babies on both days. Furthermore, the urinary NOx- excretion was significantly elevated in preterm infants with respiratory distress syndrome as compared with those without cardiopulmonary complications on the 4th day. These changes of urinary NOx- excretion in newborns strongly suggest the presence of an active physiological role for nitric oxide in the circulatory adaptation to extrauterine life.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER VERLAG  

The effectiveness of intermittent low-dose trimethoprim-sulfamethoxazole (TMP-SMZ) for the prophylaxis of recurrent urinary infection is well established in adults. The present study assessed the effectiveness and safety of intermittent low-dose TMP-SMZ in 35 children (24 boys, 11 girls, aged 1 month to 9 years, median age 5 months) with vesicoureteral reflux; 18 children had bilateral reflux. A total of 53 refluxing ureters were graded as I in 2, II in 16, III in 19, IV in 14, and V in 2 cases. The children were given 1 mg/kg body weight of trimethoprim together with 5 mg/kg of sulfamethoxazole at bedtime every other day for 6-50 months (mean +/- SD, 22.9 +/- 11.7 months). None of the boys had a recurrence of urinary infection, while 2 of the 11 girls had a total of 7 recurrences during the prophylaxis period, with a recurrence rate of 0.027 per patient month in girls. Both girls were over 3 years and had a mildly unstable bladder. Transient neutropenia (&lt;1,000/mu l) developed in 2 infants during the prophylaxis period, but disappeared spontaneously. Intermittent low-dose TMP-SMZ seemed very effective for the prevention of recurrent urinary infection in children with ureteral reflux even of higher grades.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SCANDINAVIAN UNIVERSITY PRESS  

To evaluate in vivo nitric oxide production in Kawasaki disease (KD), urinary nitrite/nitrate (NOx) excretion was measured in 8 children with KD (age 1.1-2.7 years). Urinary NOx excretion was 0.66+/-0.22 mmol mmol(-1) creatinine (mean+/-SD) in the 8 children with KD in the initial stages. The levels were significantly increased compared with those of 12 age-matched healthy control subjects (0.35+/-0.08 mmol mmol(-1) creatinine). Urinary NOx excretion was serially determined in four patients. For each patient, there was a further rise in urinary NOx excretion from baseline levels coincident with the administration of intact-type gammaglobulin and aspirin. With clinical and laboratory improvement, however, urinary NOx excretion declined to the normal range. These findings suggest that endogenous nitric oxide production is enhanced in children with acute KD. Further studies are needed to clarify the role of nitric oxide in the pathogenesis and clinical course of KD.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

We measured urinary nitrite/nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm infants aged 1 week and 1, 4, 7 months. In normal term infants, urinary NOx- excretion increased from 1 week to 1 month and then decreased until 4 months where it stabilized thereafter. Urinary NOx- excretion in preterm infants was significantly higher compared with term infants at I week of age. This finding suggests that the nitric oxide pathway in preterm infants may be activated compared with term infants in early life. With the reference values obtained in this study, this urinary marker can now be used for identifying infants with abnormal nitric oxide production.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A report is presented of a male infant with prune belly syndrome (PBS) in whom bladder enlargement was detected by ultrasound (US) as early as 13 weeks of gestation. Subsequent fetal US identified progressive urinary tract dilatation, ascites and oligohydramnios. At 22 weeks, the fetal bladder was drained under US guidance. A gradual resolution of oligohydramnios was detected on US performed after 26 weeks of gestation. Delivery by cesarean section was performed at 34 weeks of gestation. The newborn had typical features of PBS with a vesico-cutaneous fistula but did not show respiratory distress. Imaging studies showed hypoplastic left kidney, slightly dysplastic but functioning right kidney, megaureter, megacystis, vesicoureteral reflux and dilated prostatic urethra. The early detection of genitourinary system abnormalities and serial US suggest that a distal urethral obstruction may be the underlying mechanism of PBS. Spontaneous (or therapeutic) intra-uterine decompression of the bladder might ameliorate obstructive nephropathy and oligohydramnios, allowing adequate lung development. © 1997 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1997.tb03673.x

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記述言語：日本語   出版者・発行元：The Japanese Society for Pediatric Nephrology  

骨格系の代謝の基本は破骨細胞による骨吸収と骨芽細胞による骨形成の繰り返しである。これらの細胞は全身性因子の統御の下，様々な局所因子を分泌しauto-crine/paracrine 的に互いの機能調整を行っている。<br> 本稿では，その広範な生理的役割が注目されている一酸化窒素 (NO) が骨組織における強力な局所メディエータであることを支持する最近の研究成果を紹介した。とくに，成長期ラットの骨発育においてinducible型のNO合成酵素活性が重要な役割を果たすことを証明したわれわれの研究について詳述した。最後に，NOの骨代謝調節機構を対象とする研究の将来の方向性に触れた。

DOI： 10.3165/jjpn.10.17

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その他リンク： http://search.jamas.or.jp/link/ui/1997189140

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000189521

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We measured the urinary excretion of nitrite/nitrate, stable metabolites of nitric oxide, using the brucine method in 90 healthy normal children (47 boys and 43 girls), aged from 1.0 to 17.1 years, to establish the age-related normal range in children. The urinary nitrite/nitrate excretion was highest in the youngest children and decreased in an age-dependent manner to reach constant levels at about 12 years of agein both sexes. The data may be useful in identifying sick children with abnormal nitric oxide production. © 1997 S.Karger AG, Basel.

DOI： 10.1159/000190196

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Congenital maldevelopment is sometimes found in small kidneys with ureteral reflux. However, the incidence of congenitally small kidneys and the frequency of its association with ureteral reflux remains unknown. Ultrasound scanning, performed in 4,000 apparently healthy neonates or young infants (males 2,129, females 1,871), detected 51 children suspected of having small kidneys. A careful ultrasound re-examination performed one month later in 45 of the 51 children confirmed small kidneys in eight children, one bilateral and seven unilateral. Dimercaptosuccinate (DMSA) renoscintigraphy revealed small kidneys with generally diminished uptake in six infants and no uptake unilaterally in the other two infants. One of the 12 children, who had normal findings on the initial scanning and subsequently developed urinary infection, was later diagnosed having unilateral small kidney with generally reduced DMSA uptake. All seven infants having small kidneys with reduced tracer uptake were male (incidence, 1:300 boys). All eight small kidneys in the seven boys and four of the six contralateral non-small kidneys were associated with ureteral reflux, while neither of the two infants with a non- functioning kidney had ureteral reflux. Serial ultrasounds documented the poor growth of all small kidneys. Thus, congenitally small kidneys with generally diminished DMSA uptake were highly associated with ureteral reflux and especially observed in boys.

DOI： 10.1038/ki.1997.398

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing  

Objective: To investigate long-term changes of serum cholesterol levels in children with frequently relapsing steroid-responsive nephrotic syndrome (NS). Methodology: Serum cholesterol values just before and during or immediately after 'relapse' were reviewed and the incidence of hypercholesterolaemia (≤200 mg/dL) was determined in eight patients (M:F, 6:2). Results: The patients with frequently relapsing NS usually showed hypercholesterolaemia (mean incidence, 81%) just before 'relapse' during clinical remission, as well as in relapse (mean incidence, 96%). A high incidence of steroid therapy was also found in each case (mean, 89%) just before relapse. Conclusions: Our results demonstrate that children with frequently relapsing NS have prolonged periods of hypercholesterolaemia, even during clinical remission. It is suggested that serum lipid profiles be monitored carefully in such patients.

DOI： 10.1111/j.1440-1754.1997.tb01591.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000189539

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

今回の研究から,未熟児の骨代謝回転が非常に亢進していること,及び,それが児の臨床容態に応じて変化しうることが示された

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1442-200X.1996.tb03517.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Several less harmful methods than voiding cysto-urethrography for detecting significant ureteric reflux have been proposed. The present prospective study investigated whether ultrasonography was effective in identifying ureteric reflux in infants with their first febrile urinary infection. The subjects were 27 infants (24 boys and 3 girls) aged from 0 to 8 months. The urinary tract was scanned when the bladder was full, and before and during induced voiding. Infants with abnormal ultrasound findings underwent voiding cysto-urethrography. The other infants were followed and those who had a recurrence of urinary infection underwent voiding cystography. Ten children underwent cysto-urethrography, with eight refluxing ureters identified in six boys. Ultrasound revealed transient dilatation of the renal pelvis on voiding in five kidneys, transient dilatation of distal ureters in 12 and hydro-ureteronephrosis in two. Each of the five kidneys with pelvic dilatation on voiding was associated with ureteric reflux grades III or IV. Of the 17 children who did not undergo cysto-urethrography, only one had recurrence of urinary infection and was diagnosed with ureteric reflux. This girl was one of the three babies who were not scanned during voiding. More than half of the infants with febrile urinary infection were excluded from invasive examination without having recurrence of urinary infection. Thus, ultrasound scanning during voiding was effective for screening infants with their first urinary infection to detect significant ureteric reflux. 1996 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1996.tb03479.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Reflux nephropathy is known to be a major cause of renal failure in children. Vesico-ureteral reflux is usually diagnosed by voiding cysto-urethrography (VCG). However, it has been observed that conventional VCG is not always reliable for the diagnosis of ureteral reflux. In the case of a 5 year old girl with recurrent febrile urinary tract infection, VCG showed no ureteral reflux. Urodynamic study revealed a large bladder capacity and significant residual urine. Renal scintigram delineated a right renal scar. Simple ultrasound examination with videotape recording during voiding definitely demonstrated the presence of significant ureteral reflux when she voided, that is, there was marked dilatation of the right distal ureter and ballooning of the right renal pelvis on voiding, and quick refilling of the bladder concomitantly with the disappearance of the pelvic ballooning. Therefore, an ultrasound during voiding may be useful for diagnosing ureteral reflux in patients where a VCG does not reveal reflux. © 1996 Japan Pediatric Society.

DOI： 10.1111/j.1442-200X.1996.tb03510.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We evaluated the urinary excretion of selenium (Se), an essential component of glutathione peroxidase, in infants aged 1 week and 1, 4, and 7 months and examined the relationship between urinary Se and renal function. Daytime spot urine samples from a total of 80 infants were analyzed. The Se concentration in urine was measured by fluorometry, while the β2-microglobulin content, an index of renal tubular function, was determined by radioimmunoassay. In healthy term infants, the urinary Se excretion showed a peak level at 1 month of age. In contrast, the urinary Se concentration rapidly decreased in preterm infants from 1 week to 7 months postnatally. The level at 1 week in preterm infants was significantly higher than that in term infants, although the mean levels at 1 4, and 7 months were lower in preterm infants. The level of urinary Se did not correlate significantly with the β2-microglobulin concentration, either in term or preterm infants at any age investigated. Our results suggest that the renal excretion of Se probably reflects the body stores of Se and is not related directly to the renal function in infants. Urinary Se, a noninvasive marker of the Se status, may be used for diagnosis and follow-up of Se deficiency in infants. © 1996 S. Karger AG, Basel.

DOI： 10.1159/000244346

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing  

Objective: To clarify postnatal changes in urinary uric acid (UA) excretion in normal term infants and to examine the effects of prematurity or illness on the UA excretion. Methodology: Measurements of urinary UA were performed in term and premature infants at the ages of 1 and 7 days and at 1 and 4 months, as well as at 7 months in term infants. Results: Urinary UA levels were lowest on day 7 in term infants. The levels were highest on day 1 in premature infants and remained significantly higher compared to term babies during the first month of life. Respiratory failure requiring ventilation and oxygen supply resulted in further significant elevation of urinary UA in premature infants. Conclusions: With the reference values obtained in the study reported here, urinary UA can now be used for the diagnosis and monitoring of inherited disorders of purine metabolism and for the assessment of oxygen radical insult to sick infants.

DOI： 10.1111/j.1440-1754.1996.tb02564.x

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

生後1ヵ月の未熟児の尿中コラーゲン架橋(ピリジノリン,デオキシピリジノリン)排泄量を測定した.未熟児の尿中コラーゲン架橋排泄は著しく高値であった.又,それらが児の未熟性或いは臨床的容態の重篤度により,負の影響を受けることが示された

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE PUBL INC CAMBRIDGE  

The course and prognosis of idiopathic nephrotic syndrome has thus far not been found to be predicted from the severity of the manifestations at the onset. Among 66 steroid-responsive nephrotic children, eight were asymptomatic without edema and identified by chance proteinuria on a urinary screening program. The selectivity index for proteinuria (a clearance ratio of IgG to transferrin) was 0.10 or less in all of the five children examined. Ail of the eight children responded quickly to the prednisolone therapy. Grades of proteinuria and hypoalbuminemia were lower in the asymptomatic children than in the symptomatic children who presented with edema. Median proteinuria levels were 2.0 versus 4.2 g/day/m(2) (P &lt; 0.01), respectively, and mean serum albumin levels were 2.2 +/- 0.3 versus 1.8 +/- 0.4 g/dl (mean +/- SD; P &lt; 0.01), respectively. None of the eight asymptomatic children relapsed for at least one year after completion of the prednisolone treatment, while, in contrast, 30 of 58 symptomatic nephrotic children relapsed during the same one-year period (P &lt; 0.01). These findings suggest that, among steroid-responsive nephrotic children, those with mild manifestations without edema may have a milder disease and show an extremely favorable clinical course.

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記述言語：日本語   出版者・発行元：The Japanese Society for Pediatric Nephrology  

有意なVURの診断におけるエコー検査の有用性をprospectiveに検討した。初めて尿路感染症を発症した乳児27人 (男24人，女3人) を対象とした。エコー検査により，腎盂のballooningを4人の5腎で，尿管遠位部の4mm以上の拡張を10人の13尿管で，水腎水尿管症を2人の2腎で認めた。これらの所見を認めた10人にVCGを行い，6人の8腎にVURを認めた (IV度3腎，III度2腎，II度3腎)。ballooningを認めた5腎ではいずれもIII度以上のVURを認めた。II度の3腎のうち，2腎では尿管の拡張のみを認め，1腎では全く異常を認めなかった。VCGを行わなかった17人のうち，3人は排尿時のエコーによる観察ができず，尿路感染症が再発したのはこのうちの1人だけであり，再度のエコー検査によりballooningを，VCGによりVURを認めた。尿路感染症を発症した乳児のVURの一次診断として排尿時のエコー検査は極めて有用であった。

DOI： 10.3165/jjpn.8.191

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その他リンク： http://search.jamas.or.jp/link/ui/1996120493

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1442-200X.1995.tb03703.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We characterized the morphological expression of glomerular endothelial cells (GEC) cultured on a basement membrane matrix, Matrigel. GEC cultured on this matrix formed abundant networks of branching and anastomosing cords of cells, and formed capillary-like structures with a lumen and interdigitating junctional processes. In contrast, GEC cultured on fibronectin-coated dishes had elongated spindle shapes without any interdigitating junctional processes. These findings suggest that the culture system with Matrigel is useful for inducing and maintaining characteristics close to in vivo GEC. © 1994, Japanese Society of Nephrology. All rights reserved.

DOI： 10.14842/jpnjnephrol1959.36.1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Urinary N‐acetyl‐beta‐D‐glucosaminidase (NAG) excretion was measured in term and preterm neonates on days 1, 4, 7, 14 and 28 of life. Urinary NAG showed a peak level on day 4 or 7 in these infants. In addition, it tended to be higher with the degree of prematurity. In sick preterms who were depressed at birth and had respiratory failure, the NAG activity was further elevated during the first 2 weeks, suggesting the presence of renal tubular injury in this period. These observations thus suggest that urinary NAG may be a sensitive measure of renal maturation or damage in neonates. Copyright © 1994, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1440-1754.1994.tb00729.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

Although ultrasound has been recently used to estimate bladder volume, several different formulae are used. We analysed the accuracy of ultrasound evaluation of bladder volume with an ultrasound scanner equipped with a videocassette recorder. We determined three dimensions of the bladder, i.e. depth (D), height (H) and width (W) by reviewing videotapes in 53 children. D×H×W (DHW) showed a good linear relationship with actual bladder volume (r=0.96). Estimation of bladder volume by the regression equation gave errors of 12.5±8.6% (mean±SD) with errors above 25% in only 6% of children. Estimation of the volume by simply multiplying DHW by a correction factor of 0.80 gave a greater error of 18.9±14.0% (P&lt
0.001) with errors above 25% in 24% of children. Thus, the use of the formula volume (ml)=DHW (cm3)×0.68+4 was sufficiently accurate in the ultrasound estimation of bladder volume in children. © 1993 IPNA.

DOI： 10.1007/BF00852537

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

We retrospectively studied 12 Japanese children (8 boys, 4 girls) with idiopathic membranous nephropathy (IMN), aged 2.9-15.8 (mean 7.7) years at onset. All patients were identified through either screening or a routine urinalysis
proteinuria was present in all, haematuria, which was macroscopic in 4, in 11. Three had nephrotic syndrome (NS) at or soon after onset. Stages on electron microscopy, performed in 10 patients, were I in 3, II in 5 and III in 2. Steroids alone or with cyclophosphamide were administered to 5 patients, including the 3 patients showing NS. Complete remission of proteinuria occurred in 8 patients 0.3-1.6 (mean 0.6) years after onset, and proteinuria did not recur. After a follow-up of 1.6-11.6 (mean 5.9) years, these 8 patients were in complete remission and the remaining 4 had only mild proteinuria
none had hypertension or impaired renal function. Thus, we infer that IMN in Japanese children may have a better course and outcome than IMN in non-Japanese children. Based on a comparative study of Japanese (previously reported cases added to ours) and non-Japanese (mostly Caucasian) children with IMN, this was confirmed: it is possible that steroid therapy in Japanese patients is more effective in inducing remission of NS and preserving renal function. © 1993 IPNA.

DOI： 10.1007/BF00857546

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

Urinary α1-microglobulin (U-A1M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A1M was high until day 14 and declined thereafter. It was significantly correlated with urinary β2-microglobulin (U-B2M) throughout the study, but not with serum A1M on days 1 or 7. Similar to U-B2M, U-A1M in the clinically stable term infants with intrauterine growth retardation (n=4-7) was not elevated on days 1-7. In the sick infants who needed immediate resuscitatio at birth (n=4-8), U-A1M as well as U-B2M was high on days 1-7 and then decreased to normal levels, suggesting that U-A1M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A1M is a useful index of proximal tubular function in early infancy. © 1993 IPNA.

DOI： 10.1007/BF00864399

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

α 1‐Microglobulin is a low molecular weight protein that is relatively stable in urine of low pH. There have been few reports on urinary α1‐microglobulin (U‐A1M) excretion in preterm infants. This study was designed to establish the ranges for U‐A1M in clinically stable preterm infants and to investigate changes observed in sick preterm infants. We measured U‐A1M and urinary β2‐microglobulin (U‐B2M) levels at 1, 4, 7, 14, 28 and 90 days after birth in stable preterm infants (Group 1) and sick preterm infants who were depressed at birth and required immediate resuscitation (Group 2). In Group 1 infants, both parameters were high during the first 28 days and appeared to decline thereafter. U‐A1M in Group 2 infants was only significantly increased compared with Group 1 on day 1, as was U‐B2M. On each day of the study, U‐A1M had significant positive correlations with U‐B2M for all the infants studied. The changes of the two parameters observed in Group 1 probably reflect postnatal evolution of proximal tubular function in stable preterm infants. A comparison of groups 1 and 2 shows a high prevalence of acute tubular injury at birth in sick infants and also suggests that U‐A1M as well as U‐B2M may be a sensitive index for detecting acute tubular damage and for following its course in preterm infants. 1993 Japan Pediatric Society

DOI： 10.1111/j.1442-200X.1993.tb03022.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We measured urinary growth hormone (U-GH), β&lt
inf&gt
2&lt
/inf&gt
micro-globulin (U-B2) and serum growth hormone (S-GH) in preterm neonates on days 1. 4, 7, 14 and 28 of age. U-GH as well as U-B2 were high, particularly in the more premature and sick neonates with respiratory failure requiring mechanical ventilation. U-GH showed significant positive correlations with U-B2 throughout the study but with S-GH only on day 7. Therefore, we conclude that in preterm neonates, U-GH mainly reflects the degree of renal proximal tubular function, which is determined by the degree of renal maturation of the subject and of tubular injury due to disease states such as respiratory failure. © 1993 S. Karger AG, Basel.

DOI： 10.1159/000243902

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined urinary fibrin and fibrinogen degradation product (U‐FDP) concentrations in pediatric patients with hematuria using the rapid and highly‐sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non‐glomerular hematuria. If U‐FDP concentrations less than 0.25 μg/ml are Accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U‐FDP concentrations observed in patients with non‐glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U‐FDP concentrations of 0.25 μg/ml or more had coexistent erythrocyte cylindruria, the U‐FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U‐FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria. Copyright © 1992, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1992.tb01000.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1442-200X.1992.tb00933.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Herein we report an infantile case of congenital hydrocolpos combined with left renal agenesis which presented with an abnormal mass protruding from the vaginal introitus. The diagnosis was made shortly after birth by ultrasonography and confirmed by other radiologic diagnostic methods. This case highlights the value of ultrasonography in diagnosing hydrocolpos and determining the coexistence of renal anomalies. Copyright © 1991, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1991.tb02599.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Using dual‐energy x‐ray absorptiometry (DEXA), the lumbar spinal bone mineral density (BMD) in 49 Japanese children with or without metabolic bone disease (MBD) was determined. The following results were obtained: (a) The normal data for healthy Caucasians (J Clin Endocrinol Metab 1990
70: 1330‐1333) appear to be applicable to Japanese children
(b) BMD was normal in patients with congenital hydronephrosis with normal renal function
(c) One patient with congenital renal failure and one with Lowe syndrome had low BMD, but the MBD in the former improved markedly with peritoneal dialysis
(d) A reduced BMD was found in patients treated with long‐term steroids, probably because of decreased turnover of bone
(e) A reduction in BMD was pronounced in preterm infants during the first few months of life. In conclusion, DEXA is a useful method of bone densitometry in MBD in children. Copyright © 1991, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1991.tb02572.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

Renal proximal tubular function was assessed in neonates by measuring urinary β2-microglobulin (β2M) concentrations on days 1, 4, 7, 14 and 28. Values were elevated in stable preterm low-birthweight (LBW) neonates but not in stable term LBW neonates, suggesting that proximal tubular maturation is related to gestational age rather than birthweight. The urinary β2M was significantly increased on day 1 in neonates with the meconium aspiration syndrome but was not significantly different from normal subsequently. This indicated that although the proximal tubular cells may be susceptible to perinatal hypoxia, they maintain a remarkable capacity to recover in a relatively short period. Neonates with transient tachypnoea of the newborn had normal urinary levels of β2M indicating their renal tubular function was not impaired. © 1990 IPNA.

DOI： 10.1007/BF00869835

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

We compared several indices of proteinuria, namely protein concentration, hourly protein excretion rate (Up/h) and protein/creatinine ratio (Up/Ucr) in single voided urine samples as well as 24 h-urinary protein excretion (24 h-Up), in 44 children, aged 4-16 years, with varying degrees of urinary protein excretion. We found an excellent correlation between Up/h and Up/Ucr in early morning samples. These two indices in early morning samples had excellent correlation with 24 h-Up, comparable to those in any other urine sample of the day. Among daytime samples, Up/h varied widely, in contrast to Up/Ucr, which had significantly less variability. We analysed six early morning and six bedtime samples from 39 of these subjects, and found smaller coefficients of variation for individual patient's indices in morning samples. Up/h was more variable than Up/Ucr, especially in bedtime samples. Urinary protein concentration had a poorer correlation with 24 h-Up and was more variable than any other index. We conclude that the Up/Ucr in early morning samples, which has the advantages both of simplicity and low day-to-day variability in a given patient, is a superior index of proteinuria. © 1990 IPNA.

DOI： 10.1007/BF00858824

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1442-200X.1990.tb00885.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the case of an 11‐year‐old girl in whom glucosuria detected by urine screening at school was the first clue to the diagnosis of juvenile nephronophthisis (JN). On admission, she showed renal failure with combined proximal and distal tubular defects and progressive deterioration of renal function. JN should be considered in children with glucosuria. Copyright © 1990, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1990.tb00878.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The bone mineral status of very low birthweight (VLBW) infants fed exclusively their own mother's milk (group I) was compared with that of VLBW infants fed mother's milk in the initial 4 weeks followed by a 1:1 mixture of mother's milk and preterm formula containing high phosphorus (P) and calcium (Ca) (group II). In both groups, most infants showed a biochemical picture characteristic of phosphorus deficiency syndrome by the fourth week. Thereafter, serum alkaline phosphatase activity (ALP) decreased and serum P increased in all group II infants. Conversely, serum ALP rose and hypophosphatemia persisted in most group I infants. Group II had a significantly higher serum P at weeks 8 and 12 and a significantly lower ALP at week 12 than group I. Furthermore, group II had a lower incidence of severe radiographic abnormalities than group I at week 12. We confumed previous observations that VLBW infants fed exclusively human milk require P and Ca supplementation to prevent metabolic bone disease of prematurity. Copyright © 1989, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1989.tb01270.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mean cellular volume (MCV) of urinary red blood cells (RBCs) of pediatric patients with glomerular (group I
n = 52) and nonglomerular (group II
n = 21) hematuria was determined using an automated bloodell analyzer. Group I patients had a significantly lower MCV than group II (61 ± 8 w. 88 ± 15 μm3, mean ± SD
p&lt
0.001). With a MCV of 75 μm3 taken as the dividmg line between glomerular and nonglomerular hematuria, correct assessment of the site of bleeding was made in 67 of the 73 (92%) patients studied. Determination of the MCV of urinary RBCs is a simple noninvasive test for localizing the site of hemaw in pediatric patients. Copyright © 1989, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1989.tb01335.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag  

Haemolytic uraemic syndrome (HUS) associated with Yersinia enterocolitica gastroenteritis is reported in a 6-year-old girl. Y. enterocolitica of biotype 03 was isolated from the patient's initial stool sample and was subsequently identified as serotype 03 based on the rising agglutinin titres. This paper shows that yersiniosis should be suspected as a possible cause of HUS, and investigations should include the measurement of serum agglutinin titres against antigen preparations of the genus Yersinia. © 1988 IPNA.

DOI： 10.1007/BF00858683

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Biochemical and radiographic abnormalities linked with phosphorus deficiency syndrome (PDS) developed in two very low birthweight (VLBW) infants fed exclusively with human milk. By increasing phosphorus (P) and calcium (Ca) intakes with the introduction of a specialized premature formula, osteopenia or rickets, as well as hypophosphatemia, hypo‐phosphaturia and increased serum alkaline phosphatase levels improved in both patients. We speculated that all VLBW infants who are being fed exclusively with human milk should be monitored for PDS and that if PDS develops, supplementation of human milk with both P and Ca appears to be necessary for its treatment. Copyright © 1988, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-200X.1988.tb02546.x

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