Faculty Profiles - TSUKAHARA Hirokazu

Papers - TSUKAHARA Hirokazu

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Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period. Reviewed International journal

Teruo Miyazaki, Hironori Nagasaka, Haruki Komatsu, Ayano Inui, Ichiro Morioka, Hirokazu Tsukahara, Shunsaku Kaji, Satoshi Hirayama, Takashi Miida, Hiroki Kondou, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Takahiro Kodama, Kazumoto Iijima, Tohru Yorifuji, Yasushi Matsuzaki, Akira Honda

JIMD reports 43 53 - 61 2019.1

Language：English Publishing type：Research paper (scientific journal)

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

Associations of gestational age with child health and neurodevelopment among twins: A nationwide Japanese population-based study. Reviewed International journal

Kei Tamai, Takashi Yorifuji, Akihito Takeuchi, Makoto Nakamura, Yosuke Washio, Hirokazu Tsukahara, Hiroyuki Doi, Misao Kageyama

Early human development 128 41 - 47 2019.1

Language：English Publishing type：Research paper (scientific journal)

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

小児科で診療を行った摂食障害112例の特徴

岡田あゆみ, 藤井智香子, 重安良恵, 椙原彰子, 鶴丸靖子, 赤木朋子, 島内彩, 細木瑞穂, 宗盛絵里子, 塚原宏一

日本小児科学会雑誌 123 ( 1 ) 36 - 46 2019.1

Language：Japanese Publisher：(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。

Corrigendum to "Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion". Reviewed International journal

Yosuke Fujii, Masato Yashiro, Mutsuko Yamada, Tomonobu Kikkawa, Nobuyuki Nosaka, Yukie Saito, Kohei Tsukahara, Masanori Ikeda, Tsuneo Morishima, Hirokazu Tsukahara

Disease markers 2019 4025694 - 4025694 2019

Novel AVPR2 variant in a male infant with nephrogenic diabetes insipidus who showed delayed head control. Reviewed

Kosei Hasegawa, Hiromi Ihoriya, Natsuko Futagawa, Yousuke Higuchi, Hiroki Tsuchiya, Takashi Shibata, Yumiko Hayashi, Katsuhiro Kobayashi, Hirokazu Tsukahara

Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 28 ( 4 ) 155 - 158 2019

Long-stay pediatric patients in Japanese intensive care units: their significant presence and a newly developed, simple predictive score. Reviewed International journal

Emily Knaup, Nobuyuki Nosaka, Takashi Yorifuji, Kohei Tsukahara, Hiromichi Naito, Hirokazu Tsukahara, Atsunori Nakao

Journal of intensive care 7 38 - 38 2019

Language：English Publishing type：Research paper (scientific journal)

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

子どもの痛みと付き合う線維筋痛症と自閉スペクトラム症

岡田あゆみ, 椙原彰子, 堀内真希子, 藤井智香子, 重安良恵, 八代将登, 塚原宏一

Locomotive Pain Frontier 7 ( 2 ) 96 - 101 2018.12

Wernicke's encephalopathy in a child with autism during chemotherapy for T-cell acute leukemia. International journal

Kazumasa Zensho, Hisashi Ishida, Hiroki Nagai, Hirokazu Tsukahara, Akira Shimada

Pediatrics international : official journal of the Japan Pediatric Society 60 ( 8 ) 757 - 758 2018.8

Epidemiology of Pediatric Acute Encephalitis/Encephalopathy in Japan.

Shinichiro Goto, Nobuyuki Nosaka, Takashi Yorifuji, Tomoaki Wada, Yosuke Fujii, Masato Yashiro, Yosuke Washio, Kosei Hasegawa, Hirokazu Tsukahara, Tsuneo Morishima

Acta medica Okayama 72 ( 4 ) 351 - 357 2018.8

Language：English Publishing type：Research paper (scientific journal)

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

Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin Deficiency. Reviewed International journal

Satoshi Hirayama, Hironori Nagasaka, Akira Honda, Haruki Komatsu, Takahiro Kodama, Ayano Inui, Ichiro Morioka, Shunsaku Kaji, Tsuyoshi Ueno, Kenji Ihara, Mariko Yagi, Zenro Kizaki, Kazuhiko Bessho, Hiroki Kondou, Tohru Yorifuji, Hirokazu Tsukahara, Kazumoto Iijima, Takashi Miida

The Journal of clinical endocrinology and metabolism 103 ( 7 ) 2488 - 2497 2018.7

Language：English Publishing type：Research paper (scientific journal)

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

Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide. International journal

Nobuyuki Nosaka, Kazuki Hatayama, Mutsuko Yamada, Yousuke Fujii, Masato Yashiro, Hidenori Wake, Hirokazu Tsukahara, Masahiro Nishibori, Tsuneo Morishima

Journal of medical virology 90 ( 7 ) 1192 - 1198 2018.7

Language：English Publishing type：Research paper (scientific journal)

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

Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan.

Takuo Kubota, Hirofumi Nakayama, Taichi Kitaoka, Yosikazu Nakamura, Seiji Fukumoto, Ikuma Fujiwara, Yukihiro Hasegawa, Kenji Ihara, Sachiko Kitanaka, Satomi Koyama, Satoshi Kusuda, Haruo Mizuno, Keisuke Nagasaki, Koji Oba, Yuko Sakamoto, Noriyuki Takubo, Toshiaki Shimizu, Yusuke Tanahashi, Kosei Hasegawa, Hirokazu Tsukahara, Tohru Yorifuji, Toshimi Michigami, Keiichi Ozono

Endocrine journal 65 ( 6 ) 593 - 599 2018.6

Language：English Publishing type：Research paper (scientific journal)

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

心不全を契機に診断されたレニン依存性高血圧の乳児例

宮原宏幸, 宮井貴之, 平井健太, 福嶋遥輔, 重光祐輔, 榮徳隆裕, 栗田佳彦, 近藤麻衣子, 馬場健児, 塚原宏一

日本小児高血圧研究会誌 15 ( 1 ) 26 - 30 2018.6

Language：Japanese Publisher：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)

小児科長期入院における発達特性への支援小児科と子どものこころ診療部の連携による2症例

鶴丸靖子, 岡田あゆみ, 堀内真希子, 椙原彰子, 赤木朋子, 藤井智香子, 重安良恵, 塚原宏一

子どもの心とからだ 27 ( 1 ) 48 - 53 2018.5

Language：Japanese Publisher：(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)

ボタン恐怖症に認知行動療法(Cognitive behavioral therapy:CBT)を施行した1例

藤井智香子, 岡田あゆみ, 鶴丸靖子, 赤木朋子, 重安良恵, 椙原彰子, 堀内真希子, 塚原宏一

小児心身症研究 ( 25 ) 25 - 29 2018.5

Language：Japanese Publisher：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)

Birth order and paediatric allergic disease: A nationwide longitudinal survey Reviewed

T. Kikkawa, T. Yorifuji, Y. Fujii, M. Yashiro, A. Okada, M. Ikeda, H. Doi, H. Tsukahara

Clinical & Experimental Allergy 48 ( 5 ) 577 - 585 2018.5

Analysis of factors associated with development of Bacille Calmette-Guérin inoculation site change in patients with Kawasaki disease. International journal

Tooru Araki, Aya Kodera, Kunimi Kitada, Michimasa Fujiwara, Michiko Muraoka, Yoshiko Abe, Masanori Ikeda, Hirokazu Tsukahara

The Journal of international medical research 46 ( 4 ) 1640 - 1648 2018.4

Language：English Publishing type：Research paper (scientific journal)

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

Blood asymmetric dimethylarginine and nitrite/nitrate concentrations in short-stature children born small for gestational age with and without growth hormone therapy. Reviewed International journal

Hironori Nagasaka, Ichiro Morioka, Mayuko Takuwa, Mariko Nakacho, Mayumi Yoshida, Akihito Ishida, Satoshi Hirayama, Takashi Miida, Hirokazu Tsukahara, Tohru Yorifuji, Kazumoto Iijima

The Journal of international medical research 46 ( 2 ) 761 - 772 2018.2

Language：English Publishing type：Research paper (scientific journal) Publisher：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

Intrauterine and Early Postnatal Exposure to Particulate Air Pollution and Kawasaki Disease: A Nationwide Longitudinal Survey in Japan. International journal

Takashi Yorifuji, Hirokazu Tsukahara, Saori Kashima, Hiroyuki Doi

The Journal of pediatrics 193 147 - 154 2018.2

Language：English Publishing type：Research paper (scientific journal)

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

Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion. International journal

Yosuke Fujii, Masato Yashiro, Mutsuko Yamada, Tomonobu Kikkawa, Nobuyuki Nosaka, Yukie Saito, Kohei Tsukahara, Masanori Ikeda, Tsuneo Morishima, Hirokazu Tsukahara

Disease markers 2018 2380179 - 2380179 2018

Language：English Publishing type：Research paper (scientific journal)

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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