295 results on '"Toshiaki Shimizu"'
Search Results
2. Use of Head and Chest Circumference Ratio as an Index of Fetal Growth Retardation in Preterm Infants
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Hiromichi Shoji, Yayoi Murano, Yukika Saitoh, Naho Ikeda, Natsuki Ohkawa, Naoto Nishizaki, Ken Hisata, Masato Kantake, Kaoru Obinata, Daisuke Yoneoka, and Toshiaki Shimizu
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Fetal Growth Retardation ,Nutrition and Dietetics ,head circumference to chest circumference ratio ,very low birth weight infants ,fetal growth restriction ,body mass index ,Infant, Newborn ,Infant ,Humans ,Infant, Very Low Birth Weight ,Female ,Gestational Age ,Child ,Infant, Premature ,Body Height ,Food Science - Abstract
We evaluated the relationship between fetal growth in preterm babies using the head circumference (HC)/chest circumference (CC) ratio and other anthropometric parameters at birth and at school age. Data were collected from 187 very low birth weight (VLBW) children born at less than 30 weeks of gestational age (GA) at birth and at 6 years. We assessed the correlation between the HC/CC ratio and body weight (BW), body length (BL), and HC z-scores at birth, and BW, body height (BH), and body mass index (BMI) z-scores at 6 years. Multiple regression analysis showed that BW z-score, BL z-score, and HC z-score at birth were significantly associated with HC/CC at birth. The BMI z-score at 6 years was also significantly associated with HC/CC at birth. The HC/CC ratio at birth is a reliable parameter for evaluating fetal growth restriction and a possible predictor of physical growth in VLBW children.
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- 2022
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3. A Possible Association Between a Nucleotide‐Binding Domain LRR‐Containing Protein Family PYD‐Containing Protein 1 Mutation and an Autoinflammatory Disease Involving Liver Cirrhosis
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Junko Takita, Toshiaki Shimizu, Ayako Kaitani, Hideoki Ogawa, Anna Kamei, Kenichi Yoshida, Junichi Kaneko, Nobuhiro Nakano, Hexing Wang, Koichiro Uchida, Masafumi Seki, Shigeru Nomura, Tomoaki Ando, Kiyoshi Hasegawa, Hiroki Yasudo, Seishi Ogawa, Yoko Okamoto, Nobuyuki Ebihara, Akie Maehara, Kumi Izawa, Ko Okumura, Mayuki Kojima, Hirotsugu Oda, Naoto Tamura, Atsushi Tanabe, Taiki Ando, Meiko Kimura, and Jiro Kitaura
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Liver Cirrhosis ,0301 basic medicine ,Cirrhosis ,Adolescent ,Protein family ,Inflammasomes ,Autoimmunity ,NLR Proteins ,Biology ,03 medical and health sciences ,Papillon-Lefevre Disease ,0302 clinical medicine ,medicine ,Humans ,Autoinflammatory disease ,Genetics ,Hepatology ,Interleukin-18 ,Inflammasome ,medicine.disease ,Liver Transplantation ,Treatment Outcome ,030104 developmental biology ,Liver ,Cyclic nucleotide-binding domain ,Mutation ,Mutation (genetic algorithm) ,Female ,030211 gastroenterology & hepatology ,Interleukin 18 ,medicine.drug - Published
- 2021
4. A randomized trial to examine the impact of food on pharmacokinetics of 4-phenylbutyrate and change in amino acid availability after a single oral administration of sodium 4-phenylbutyrarte in healthy volunteers
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Hiroyuki Kusuhara, Mitsuyoshi Suzuki, Yoshiki Miura, Shuhei Osaka, Yusuke Sabu, Hisamitsu Hayashi, Ayumu Mizutani, Satoshi Nakano, Kei Minowa, Yuka Hiraoka, Tadahaya Mizuno, Saeko Hirai, and Toshiaki Shimizu
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Adult ,Male ,0301 basic medicine ,Glutamine ,Endocrinology, Diabetes and Metabolism ,Administration, Oral ,Biological Availability ,030105 genetics & heredity ,Pharmacology ,Biochemistry ,Phenylbutyrate ,Eating ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pharmacokinetics ,Oral administration ,Genetics ,Humans ,Medicine ,Amino Acids ,Urea Cycle Disorders, Inborn ,Molecular Biology ,Meal ,business.industry ,Middle Aged ,Phenylbutyrates ,Crossover study ,Healthy Volunteers ,Regimen ,Urea cycle ,Female ,business ,Amino Acids, Branched-Chain ,030217 neurology & neurosurgery - Abstract
Urea cycle disorders (UCDs), inborn errors of hepatocyte metabolism, result in the systemic accumulation of ammonia to toxic levels. Sodium 4-phenylbutyrate (NaPB), a standard therapy for UCDs for over 20 years, generates an alternative pathway of nitrogen deposition through glutamine consumption. Administration during or immediately after a meal is the accepted use of NaPB. However, this regimen is not based on clinical evidence. Here, an open-label, single-dose, five-period crossover study was conducted in healthy adults to investigate the effect of food on the pharmacokinetics of NaPB and determine any subsequent change in amino acid availability. Twenty subjects were randomized to one of four treatment groups. Following an overnight fast, NaPB was administered orally at 4.3 g/m2 (high dose, HD) or 1.4 g/m2 (low dose, LD) either 30 min before or just after breakfast. At both doses, compared with post-breakfast administration, pre-breakfast administration significantly increased systemic exposure of PB and decreased plasma glutamine availability. Pre-breakfast LD administration attenuated plasma glutamine availability to the same extent as post-breakfast HD administration. Regardless of the regimen, plasma levels of branched-chain amino acids (BCAA) were decreased below baseline in a dose-dependent manner. In conclusion, preprandial oral administration of NaPB maximized systemic exposure of the drug and thereby its potency to consume plasma glutamine. This finding may improve poor medication compliance because of the issues with odor, taste, and pill burden of NaPB and reduce the risk of BCAA deficiency in NaPB therapy.
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- 2021
5. Unsatisfactory Short-Term Neurodevelopmental Outcomes of Preterm Infants Who Received Polymyxin B-Immobilized Fiber Column-Direct Hemoperfusion for Septic Shock
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Kaoru Obinata, Taiki Shima, Akiko Watanabe, Naoto Nishizaki, and Toshiaki Shimizu
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Adult ,Male ,endocrine system ,medicine.medical_treatment ,Nervous System ,Polymyxin b immobilized fiber ,General Biochemistry, Genetics and Molecular Biology ,Sepsis ,Interquartile range ,medicine ,Humans ,Polymyxin B ,Periventricular leukomalacia ,Septic shock ,business.industry ,Infant, Newborn ,General Medicine ,medicine.disease ,Hemoperfusion ,Shock, Septic ,Intraventricular hemorrhage ,Shock (circulatory) ,Anesthesia ,Female ,medicine.symptom ,business ,Infant, Premature - Abstract
Sepsis and septic shock are associated with high mortality and neurodevelopmental impairment in preterm infants. Recently, endotoxin and mediator removal using a polymyxin B-immobilized fiber column for direct hemoperfusion (PMX-DHP) has been used for the management of septic shock even in neonates. Although early withdrawal from shock with PMX-DHP contributes to survival, its effect on neurodevelopment after discharge is unclear. This study aimed to examine short-term neurodevelopmental impairment in preterm infants with septic shock who were treated with PMX-DHP. We retrospectively assessed five infants who received treatment with PMX-DHP (median 25.5 [interquartile range: 24.8-28.3] weeks and 817 [interquartile range: 667-954] g). Neurodevelopmental outcomes were assessed with the Kyoto Scale of Psychological Development 2001 at a median 34.5 (interquartile range: 29.5-44.5) months of corrected age after discharge. The short-term neurodevelopmental prognosis of preterm infants treated with PMX-DHP for septic shock was delayed (overall developmental quotient < 70) with an average quotient of 57.3. Furthermore, four (80%) of five patients presented with intraventricular hemorrhage and another four (80%) with periventricular leukomalacia. In conclusion, preterm infants with septic shock treated with PMX-DHP had unsatisfactory short-term neurodevelopmental outcomes. Hence, the effect of PMX-DHP in improving neurodevelopmental prognosis even in preterm infants with septic shock should be further evaluated.
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- 2021
6. Effectiveness of Biological Agents in the Treatment of Pediatric Patients with Crohn’s Disease and Anal Fistulae
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Kazuhide Tokita, Nobuyasu Arai, Tamaki Ikuse, Eri Miyata, Takahiro Kudo, Reiko Kyodo, Toshiaki Shimizu, Keisuke Jimbo, Yoshikazu Ohtsuka, Masamichi Sato, and Kenji Hosoi
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Male ,Anal fistula ,medicine.medical_specialty ,Elemental diet ,medicine.medical_treatment ,Disease ,Biological Factors ,Crohn Disease ,Quality of life ,Induction therapy ,medicine ,Humans ,Rectal Fistula ,Child ,Retrospective Studies ,Crohn's disease ,business.industry ,Medical record ,Gastroenterology ,Colostomy ,medicine.disease ,Surgery ,Cross-Sectional Studies ,Treatment Outcome ,Quality of Life ,Female ,business - Abstract
Introduction: Anal fistulae have a significant impact on the quality of life of patients with Crohn’s disease (CD). In this cross-sectional study, we aimed to determine whether biological agents were effective in treating anal fistulae in patients with CD. Methods: Fifty-three patients diagnosed with CD were retrospectively enrolled. Their data regarding symptoms, treatments, and disease progression from January 2007 to December 2016 were reviewed from the medical records. Fifteen (28%) patients with CD were complicated by anal fistulae. Results: The male-to-female ratio was 13:2, and the mean age at onset was 11 years and 6 months. Among the 15 patients, 14 (93%) had anal fistulae as an initial symptom. Almost all patients were treated by providing elemental diet, 5-aminosalicylic acid, and steroids as induction therapy. Biological agents were used in 8 patients (53.3%), and fistula closure was confirmed in all of them. Among the 7 patients not treated with biological agents, 1 (14.3%) had a recurrent anal fistula, while another had incomplete fistula closure. Regarding surgical management, 2 patients were treated using the seton method, and no patients required a colostomy. Conclusion: Treatment with biological agents is highly effective concerning the closure of anal fistulae in patients with CD, and reducing pain may improve their quality of life.
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- 2021
7. Left atrial dysfunction and stiffness in pediatric and adult patients with Type 1 diabetes mellitus assessed with speckle tracking echocardiography
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Noriyuki Takubo, Hidenori Haruna, Hirotaka Watada, Kouji Komiya, Ken Takahashi, Mayumi Ifuku, Takeshi Iso, Yu Hosono, Toshiaki Shimizu, Fuki Ikeda, Mika Kurita, and Akimi Ishikawa
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Diabetic Cardiomyopathies ,Endocrinology, Diabetes and Metabolism ,Diastole ,Speckle tracking echocardiography ,Young Adult ,Internal medicine ,Diabetic cardiomyopathy ,Internal Medicine ,medicine ,Humans ,Prospective Studies ,Young adult ,Child ,Subclinical infection ,Type 1 diabetes ,business.industry ,medicine.disease ,Diabetes Mellitus, Type 1 ,medicine.anatomical_structure ,Echocardiography ,Ventricle ,Case-Control Studies ,Child, Preschool ,Heart failure ,Pediatrics, Perinatology and Child Health ,Cardiology ,Atrial Function, Left ,Female ,business - Abstract
Background Subclinical diastolic dysfunction in patients with type 1 diabetes mellitus (T1DM) caused by myocardial injury due to diabetic cardiomyopathy leads to a high risk of death and heart failure. This myocardial injury extends not only to the left ventricle (LV) but also to the left atrium (LA). However, LA function in children and young adults with T1DM has not been extensively studied. Objective Therefore, the aim of this study was to assess LA dysfunction in pediatric and adult patients with T1DM usingLA strain analysis withechocardiography. Subjects Fifty-three patients (median age: 23 [range: 5-41] years) with T1DM. Methods We dividedthe patients into three age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-41 years);53 age- and sex-matched controls were divided into three corresponding groups (C1, C2, and C3). LA and LV functions were evaluated usingechocardiography. Results LA reservoir strain was lower in the D2 and D3 groups than in the C2 and C3 groups (p = 0.001, p = 0.004, respectively). LA conduit strain was lower in the D2 group thanin the C2 group (p = 0.002). LA stiffness wassignificantlygreater in the D3 groupthan in the C3 group (p Conclusions In patients with T1DM, LA phasic function decreased in adolescents and young adults, and LA stiffness increased in adult patients aged>30 years. LA phasic function and LA stiffness can be potentially used as early markers for diastolic dysfunction. This article is protected by copyright. All rights reserved.
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- 2020
8. Comparison of time to positivity of pediatric blood cultures obtained within the first year of life and in later years
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Toshiaki Shimizu, Hiroyuki Sato, Yoshiyuki Otomo, Keiya Sato, Shinichi Niijima, and Akihiro Nakao
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Male ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Time Factors ,Adolescent ,030106 microbiology ,Bacteremia ,First year of life ,medicine.disease_cause ,Teaching hospital ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Blood culture ,030212 general & internal medicine ,Child ,Time to positivity ,Retrospective Studies ,Bacteriological Techniques ,Bacteria ,medicine.diagnostic_test ,business.industry ,Age Factors ,Infant ,Pathogenic bacteria ,Pediatric age ,medicine.disease ,Blood ,Infectious Diseases ,Blood Culture ,Child, Preschool ,Female ,business - Abstract
The time to positivity (TTP) of blood culture has significant value for clinicians. However, almost all subjects of previous studies regarding TTP were adults and early infants. Therefore, careful attention is required when referring to previously published data, which might differ according to the age of subjects, as the tendency of infectious focus and pathogens identified from culture vary with age. In this study, we compared the TTP between two pediatric age groups (≤12 months and 13 months to 15 years [12 months]) at a teaching hospital during a 5-year period. Of the 95 subjects, 41 and 54 were aged ≤12 and 12 months, among whom true pathogenic bacteria were identified in 12 (29.3%) and 19 (35.2%), respectively. The median TTP for the younger group with pathogenic bacteria was 11.2 (interquartile range, 10.0-11.9) hours, which was significantly shorter than that for the older group (12.6 [interquartile range, 11.9-16.9] hours) (P = 0.01). At 12 h after the initiation of culture, the younger group with pathogenic bacteria had a significantly higher positivity rate (83.3%) than the older group (26.3%) (P 0.01). The times required for the positivity to exceed 90% were 13.4 and 20.1 h for the younger and older pathogenic groups and 30.4 and 67.8 h for the younger and older contaminant groups, respectively. The range of TTP could be assessed more accurately by considering the effect of age on the infectious background.
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- 2020
9. A novel segmental absence of intestinal musculature with small intestinal stenosis: a case report
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Kosuke Kashiwagi, Takahiro Kudo, Go Miyano, Toshiaki Shimizu, Keisuke Jimbo, Atsuyuki Yamataka, and Kenji Hosoi
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Adult ,Crohn’s disease ,medicine.medical_specialty ,Abdominal pain ,Creeping fat sign ,Perforation (oil well) ,Case Report ,Constriction, Pathologic ,Capsule Endoscopy ,Gastroenterology ,law.invention ,03 medical and health sciences ,Ileocecal valve ,0302 clinical medicine ,Crohn Disease ,Capsule endoscopy ,law ,Internal medicine ,Small Intestinal Stenosis ,medicine ,Humans ,lcsh:RC799-869 ,Child ,Ultrasonography ,Crohn's disease ,medicine.diagnostic_test ,business.industry ,Power Doppler ,Infant, Newborn ,General Medicine ,medicine.disease ,Intestines ,Stenosis ,medicine.anatomical_structure ,Child, Preschool ,030220 oncology & carcinogenesis ,Abdominal ultrasonography ,Female ,030211 gastroenterology & hepatology ,lcsh:Diseases of the digestive system. Gastroenterology ,medicine.symptom ,business ,Intestinal Obstruction - Abstract
Background Segmental absence of intestinal musculature (SAIM) is a rare cause of intestinal obstruction and perforation due to partial or complete defects in the intestinal muscularis propria in neonates and is occasionally observed in adulthood. Case presentation The first case of small intestinal stenosis derived from SAIM, which was difficult to differentiate from Crohn’s disease (CD), is reported. A 4-year-old girl presented with abdominal pain, anemia, and a positive fecal occult blood test. She was initially diagnosed with CD and started on treatment. Because her gastrointestinal symptoms persisted, her previous pediatricians tried to carry out capsule endoscopy, but it was not possible because the patency capsule was retained. Therefore, she was referred to our institute and re-evaluated. The patency capsule examination was repeated to re-evaluate small intestinal passage, but it stagnated again. Abdominal ultrasonography showed a poorly deformable intestinal tract that narrowed rapidly from the dilated segment and had a thin wall with an irregular laminar structure. In addition, unlike the typical ultrasonic CD findings, the power Doppler signal enhancement at the intestinal wall and “creeping fat sign” were not found. The patient was referred for laparoscopic observation to pediatric surgeons, who confirmed a prominently dilated intestinal tract 40 cm proximal to the ileocecal valve, which was resected. Histopathological findings showed longitudinal muscle hypoplasia of the resected, dilated intestinal tract and fat replacement of the muscle layer. At the stenosis site, the muscle layer was fibrotic and showed incomplete muscle arrangement. Because of these findings, she was diagnosed with SAIM. After the surgical treatment, no gastrointestinal symptoms relapsed, and the fecal occult blood test has remained negative for 2 years. Moreover, 8 months after surgery, double-balloon endoscopy showed no abnormalities, such as a longitudinal ulcer and cobblestone appearance. Conclusions In the present case, SAIM involved not only intestinal ileus and perforation, but also small intestinal stenosis. Although no other reports have demonstrated the usefulness of abdominal ultrasonography for the diagnosis of SAIM, the present report suggests that ultrasonography may be useful for differentiating SAIM from CD by close observation of the area around the small intestinal stenosis.
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- 2020
10. Decreased peripheral blood memory B cells are associated with the presence of interstitial lung disease in rheumatoid arthritis: a case-control study
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Shoko Tateishi, Hirofumi Shoda, Hiroaki Harada, Toshiaki Shimizu, Yasuo Nagafuchi, Norio Hanata, Kazuhiko Yamamoto, Shuji Sumitomo, Haruka Tsuchiya, Yumi Tsuchida, Keishi Fujio, and Hiroko Kanda
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Adult ,Male ,Naive B cell ,B-Lymphocyte Subsets ,Immunologic Tests ,Flow cytometry ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Rheumatology ,medicine ,Humans ,030212 general & internal medicine ,Lung ,030203 arthritis & rheumatology ,B-Lymphocytes ,medicine.diagnostic_test ,business.industry ,Case-control study ,Interstitial lung disease ,medicine.disease ,Peripheral blood ,Case-Control Studies ,Rheumatoid arthritis ,Immunology ,Prednisolone ,Female ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,business ,Immunologic Memory ,medicine.drug - Abstract
Objectives: Interstitial lung disease sometimes occurs in rheumatoid arthritis patients. Although the underlying immunological mechanisms responsible for interstitial lung disease associated with rheumatoid arthritis have not yet been clarified, some reports have suggested possible roles of B cells. To examine the role of B-cell subsets in interstitial lung disease in rheumatoid arthritis patients, we analyzed peripheral blood B-cell subsets.Methods: We analyzed the frequencies of the peripheral blood B-cell subsets by flow cytometry in rheumatoid arthritis patients with and without interstitial lung disease (n = 16 and 81, respectively) and in healthy donors (n = 110) by high-resolution computed tomography.Results: Compared with healthy donors, rheumatoid arthritis patients showed statistically higher frequencies of naive B cells and lower frequencies of memory B cells. Moreover, the frequencies of memory B cells were lower in rheumatoid arthritis patients with interstitial lung disease than in those without. Multivariate analysis showed that the frequency of memory B cells, particularly switched memory B cells, was significantly decreased in rheumatoid arthritis patients with interstitial lung disease, even after adjusting for prednisolone dose.Conclusions: We suspect memory B cells play important roles in interstitial lung disease associated with rheumatoid arthritis.
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- 2020
11. The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants
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Akiko Watanabe, Toshiyuki Yoneyama, Akina Matsuda, Kaoru Obinata, Naoto Nishizaki, and Toshiaki Shimizu
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Male ,medicine.medical_specialty ,Urinary system ,Indomethacin ,Renal function ,Ibuprofen ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,Gastrointestinal complications ,0302 clinical medicine ,Japan ,030225 pediatrics ,Ductus arteriosus ,Internal medicine ,medicine ,Birth Weight ,Humans ,Adverse effect ,Ductus Arteriosus, Patent ,business.industry ,Incidence (epidemiology) ,Anti-Inflammatory Agents, Non-Steroidal ,Infant, Newborn ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,medicine.anatomical_structure ,Intraventricular hemorrhage ,Infant, Extremely Low Birth Weight ,Case-Control Studies ,Pediatrics, Perinatology and Child Health ,Female ,business ,Infant, Premature ,medicine.drug - Abstract
Background Ibuprofen (IBU) has been used recently for the treatment of patent ductus arteriosus (PDA) in Japan. We aimed to investigate the efficacy and adverse events of IBU and compare them with those of indomethacin (IND) as PDA treatment for extremely low-birthweight infants (ELBWIs), focusing on short-term renal function. Methods A case-control study was conducted on 16 ELBWIs. The data from eligible patients were divided into two groups. Ten patients had undergone IND treatment (IND group) between January 2017 and June 2018, whereas six had undergone IBU treatment (IBU group) for PDA between July 2018 and December 2018. The IND group received 0.1 mg/kg/12h IND IV infusion for three doses, whereas the IBU group received 10 mg/kg IV IBU infusion followed by 5 mg/kg/day for 2 days. We compared the efficacy for PDA closure and renal impairment between the two groups. Results No significant differences in primary closure rates and the PDA ligation required were observed between the two groups. No significant differences were observed between the incidence of intraventricular hemorrhage and gastrointestinal complications in both groups. Changes in urine volume (%) in the IBU group were significantly higher than in the IND group at 24-36 h post-administration. The urinary L-type fatty acid binding protein concentration level at 7 days of life was significantly lower in the IBU group than in the IND group. Conclusion Although IBU was comparable to IND in PDA closure rate, IBU was superior to short-term renal injury in ELBWIs.
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- 2020
12. Policy statement of enteral nutrition for preterm and very low birthweight infants
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Nobuo Yoshiike, Shinobu Ida, Toshihiro Ohura, Akihide Sugiyama, Kazue Kawakami, Daisuke Tanaka, Yuko Bito, Chiharu Tsutsumi, Akihisa Okumura, Katsumi Mizuno, Sotaro Mushiake, Toru Kikuchi, Mitsuyoshi Suzuki, Yoshio Hanawa, Kimitaka Takitani, Kazuo Okada, Motoichiro Sakurai, Masanobu Kawai, Mikako Inokuchi, Hiroko Kodama, Mitsuhiko Hara, Hiroaki Inomata, Tatsuya Oguni, Setsuko Ito, Shigetaka Sugihara, Keiichi Uchida, and Toshiaki Shimizu
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medicine.medical_specialty ,Medical staff ,Human milk bank ,Mothers ,030204 cardiovascular system & hematology ,Breast milk ,Guidelines ,03 medical and health sciences ,0302 clinical medicine ,fluids and secretions ,Enteral Nutrition ,Japan ,030225 pediatrics ,medicine ,donor human milk ,Humans ,Infant, Very Low Birth Weight ,Infant Nutritional Physiological Phenomena ,human milk bank ,Milk, Human ,Obstetrics ,business.industry ,Infant, Newborn ,food and beverages ,human milk ,Infant ,Guideline ,Human milk fortifier ,Parenteral nutrition ,Milk Banks ,Pediatrics, Perinatology and Child Health ,exclusive human milk-based diet ,Female ,business ,Infant, Premature - Abstract
For preterm and very low birthweight infants, the mother’s own milk is the best nutrition. Based on the latest information for mothers who give birth to preterm and very low birthweight infants, medical staff should encourage and assist mothers to pump or express and provide their own milk whenever possible.If the supply of maternal milk is insufficient even though they receive adequate support, or the mother’s own milk cannot be given to her infant for any reason, donor human milk should be used.Donors who donate their breast milk need to meet the Guideline of the Japan Human Milk Bank Association.Donor human milk should be provided according to the medical needs of preterm and very low birthweight infants, regardless of their family’s financial status.In the future, it will be necessary to create a system to supply an exclusive human milk‐based diet (EHMD), consisting of human milk with the addition of a human milk‐derived human milk fortifier, to preterm and very low birthweight infants.
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- 2020
13. Granulomatous vasculitis of the esophagus in a girl with odynophagia
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Itsuhiro Oka, Yoshiyuki Ohtomo, and Toshiaki Shimizu
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Vasculitis ,Pediatrics, Perinatology and Child Health ,Esophagitis ,Humans ,Female ,Herpes Simplex ,Thorax ,Deglutition Disorders - Published
- 2022
14. The developmental origins of health and chronic kidney disease: Current status and practices in Japan
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Naoto Nishizaki and Toshiaki Shimizu
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Adult ,Proteinuria ,Japan ,Pregnancy ,Pediatrics, Perinatology and Child Health ,Infant, Newborn ,Humans ,Infant ,Female ,Acute Kidney Injury ,Renal Insufficiency, Chronic ,Kidney - Abstract
The concept of the developmental origins of health and disease (DOHaD) views unfavorable perinatal circumstances as contributing to the development of diseases in later life. It is well known that such unfavorable circumstances play an important role as a risk factor for chronic kidney disease (CKD) in infants born with prematurity. Low birthweight (LBW) is believed to be a potential contributor to CKD in adulthood. Preterm and/or LBW infants are born with incomplete nephrogenesis. As a result, the number of nephrons is low. The poor intrauterine environment also causes epigenetic changes that adversely affect postnatal renal function. After birth, hyperfiltration of individual nephrons due to low nephron numbers causes proteinuria and secondary glomerulosclerosis. Furthermore, the risk of CKD increases as renal damage takes a second hit from exposure to nephrotoxic substances and acquired insults such as acute kidney injury after birth among infants in neonatal intensive care. Meanwhile, unfortunately, recent studies have shown that the number of nephrons in healthy Japanese individuals is approximately two-thirds lower than that in previous reports. This means that Japanese premature infants are clearly at a high risk of developing CKD in later life. Recently, several DOHaD-related CKD studies from Japanese researchers have been reported. Here, we summarize the relevance of CKD in conjunction with DOHaD and review recent studies that have examined the impact of the upward LBW trend in Japan on renal health.
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- 2022
15. Gender disparities in the pediatric allergy‐related guidelines in Japan
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Shun Toriumi, Hiromichi Yamada, Eisuke Inage, Yuko Tanaka, Yosuke Baba, Takahiro Kudo, Mayuki Kojima, Toshiaki Shimizu, and Kotoko Matsui
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medicine.medical_specialty ,Allergy ,business.industry ,Disease ,Atopic dermatitis ,Guideline ,medicine.disease ,Rhinitis, Allergic ,Asthma ,Dermatitis, Atopic ,Japan ,Food allergy ,Family medicine ,Pediatrics, Perinatology and Child Health ,Humans ,Medicine ,Female ,Pediatric allergy ,Child ,business ,Food Hypersensitivity ,Pediatric asthma - Abstract
BACKGROUND Inclusion of female authors has been noted as potentially beneficial in the development of medical guidelines. Japanese professional committees representing allergic subspecialties develop practical guidelines with recommendations to caregivers, but these committees may be influenced by their gender composition. The objective of our study was to examine the influence of gender in developing pediatric allergic disease guidelines in Japan from 1999 to 2020. METHODS We examined the gender differences among the guideline committee members: allergic rhinitis, atopic dermatitis, bronchial asthma, and food allergies in Japan. We examined the gender composition of the committees, annual trends, and differences in guideline content. RESULTS The median proportion of women members among the 22 guidelines committees was 6.6% (range: 0%-27.3%). The analysis of the quadrant period did not show a significant increase in the proportion of female members. The food allergy group had a significantly higher proportion of female members than other guidelines (P < 0.01), but the proportion decreased from 25% to 14.3% during the observation period. For the pediatric asthma guidelines, the proportion of female committee members decreased from 5.3% in the 2000 version to 0% in the most recent revision in 2017. CONCLUSIONS The proportion of women on the committees that develop pediatric guidelines continues to be low and has not improved over the past 20 years.
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- 2022
16. Infliximab for very early‐onset inflammatory bowel disease: A tertiary center experience in Japan
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Hirotaka Shimizu, Toshiaki Shimizu, Satoru Nagata, Yuri Hirano, Yoichiro Kaburaki, Katsuhiro Arai, and Ichiro Takeuchi
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Inflammatory bowel disease ,Tertiary Care Centers ,Young Adult ,fluids and secretions ,Gastrointestinal Agents ,Japan ,Refractory ,Internal medicine ,medicine ,Humans ,Infusion reaction ,Child ,Retrospective Studies ,Anus Diseases ,Hepatology ,business.industry ,Medical record ,Age Factors ,Gastroenterology ,Infant ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,Infliximab ,digestive system diseases ,Treatment Outcome ,Child, Preschool ,Cohort ,Colitis, Ulcerative ,Female ,Premedication ,business ,medicine.drug - Abstract
Background and aim Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed before 6 years of age, tends to be refractory to conventional treatment for IBD. However, there have been a few reports about the usage of infliximab for VEO-IBD. This study aimed to evaluate the efficacy and safety of infliximab for VEO-IBD. Methods Medical records of a cohort of children with VEO-IBD who had received infliximab in a Japanese tertiary children's hospital were retrospectively reviewed for their disease characteristics and clinical course. Subjects were categorized into three groups for the descriptive comparison: ulcerative colitis type (UCT), non-UCT with perianal disease (NUC-PD), and non-UCT without perianal disease (NUC-NPD). Results Seventeen VEO-IBD patients (five UCT, five NUC-PD, and seven NUC-NPD) had received infliximab as their first biologic. In the UCT group, infliximab was continued over 54 weeks in two patients, and three eventually required surgery. In contrast, all patients in the NUC-PD and NUC-NPD groups followed up over 54 weeks remained on infliximab, and two of three patients and three of five patients were in remission at week 54, respectively. Infusion reactions occurred in all five UCT, three of five NUC-PD, and two of seven NUC-NPD patients; however, except for two patients with severe reactions, infliximab was continued with premedication and slow infusions. Conclusions Infliximab appeared useful for children with VEO-IBD. Children with NUC-PD and NUC-NPD responded better with less infusion reaction compared with that with UCT.
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- 2019
17. Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers
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Mitsuyoshi Suzuki, Yuko Sakamoto, Satoshi Nakano, Akifumi Tokita, Masahiko Nozawa, Muneaki Ishijima, Lizu Liu, Sung-Gon Kim, Kazuo Kaneko, and Toshiaki Shimizu
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Genu varum ,Parathyroid hormone ,030209 endocrinology & metabolism ,Rickets ,Gastroenterology ,Phosphates ,Young Adult ,03 medical and health sciences ,Child Development ,0302 clinical medicine ,Endocrinology ,Japan ,Genu Varum ,Internal medicine ,Prevalence ,medicine ,Vitamin D and neurology ,Humans ,Blood test ,Orthopedics and Sports Medicine ,Vitamin D ,Child ,medicine.diagnostic_test ,business.industry ,Metabolic disorder ,Age Factors ,Odds ratio ,Alkaline Phosphatase ,Vitamin D Deficiency ,medicine.disease ,body regions ,Bone Diseases, Metabolic ,Parathyroid Hormone ,Case-Control Studies ,Child, Preschool ,Alkaline phosphatase ,Calcium ,Female ,030101 anatomy & morphology ,medicine.symptom ,business - Abstract
When children around 2-year-old show leg bowing without lower-limb radiographic abnormalities for rickets, the leg bowing is classified as “physiologic” genu varum without conducting a blood test. However, it has recently been suggested that toddlers who are diagnosed with physiologic genu varum may in fact have some form of bone metabolic disorder. In this 1:2 case–control study, blood samples were obtained from 33 toddlers with genu varum without radiographic abnormalities for rickets and 66 age- and gender-matched healthy children. Serum alkaline phosphatase (sALP), intact parathyroid hormone (siPTH), 25-hydroxy vitamin D [s25(OH)D], calcium (sCa), and inorganic phosphate (sP) were measured. s25(OH)D of the subjects with genu varum (24.8 ng/ml) were significantly lower than those of the control (33.6 ng/ml) (p
- Published
- 2019
18. Perforation in pediatric non-complicated appendicitis treated by antibiotics: the real incidence
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Go Miyano, Ryohei Kuwatsuru, Shiho Yoshida, Takanori Ochi, Seitaro Kosaka, Kazuhiro Suzuki, Geoffrey J. Lane, Atsuyuki Yamataka, Hiroyuki Koga, Takafumi Mikami, Ryo Sueyoshi, Keisuke Jimbo, Tadaharu Okazaki, Toshiaki Shimizu, Masahiko Urao, and Toshihiro Yanai
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Male ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Antibiotics ,Perforation (oil well) ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Pediatric surgery ,medicine ,Appendectomy ,Humans ,Child ,Retrospective Studies ,Ultrasonography ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,General Medicine ,Complicated appendicitis ,Appendicitis ,Anti-Bacterial Agents ,Child, Preschool ,Abdominal ultrasonography ,Pediatrics, Perinatology and Child Health ,Acute appendicitis ,Female ,030211 gastroenterology & hepatology ,Surgery ,Radiology ,Emergencies ,Triage ,Tomography, X-Ray Computed ,business ,Complication - Abstract
The incidence of perforation during antibiotic therapy (AT) of children triaged as non-complicated acute appendicitis (NC-Ap) was investigated. Abdominal ultrasonography (US) and/or computed tomography (CT) scans from cases of perforation identified at appendectomy for failed AT were reassessed blindly by a panel of board-certified specialists for any evidence of pre-AT morbidity suggestive of perforation. Of 521 cases triaged as NC-Ap, symptoms resolved with AT in 452 cases (86.8%). All 69/521 (13.2%) cases with persistent symptoms had urgent appendectomy, and 12/521 (2.3%) were found to have perforated. Blind reassessment of US and/or CT scans from these cases identified seven with evidence of perforation when they were triaged as NC-Ap. Thus, the actual incidence of perforation during AT for NC-Ap was actually 12–7 = 5/521 (0.95%). Perforation is generally believed to be a complication of AT, but inappropriate triaging of cases for AT can bias results by artificially inflating the number of perforations, in this study, by more than double. We are the first to assess the unbiased incidence of perforation during AT for NC-Ap, by reassessing pre-AT US and/or CT scans. The incidence of perforation during AT is actually negligible.
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- 2019
19. Neonatal oral fluid as a transmission route for bifidobacteria to the infant gut immediately after birth
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Ken Hisata, Kohzo Aisaka, Noriko Katsumata, Tetsuya Kuhara, Jin-zhong Xiao, Toshitaka Odamaki, Toshiaki Shimizu, Kazuya Toda, Takane Katayama, Takumi Satoh, and Eri Mitsuyama
- Subjects
Male ,0301 basic medicine ,Physiology ,lcsh:Medicine ,Infant health ,Gut flora ,digestive system ,Article ,Feces ,03 medical and health sciences ,0302 clinical medicine ,fluids and secretions ,Species Specificity ,RNA, Ribosomal, 16S ,Bifidobacteriales Infections ,Cluster Analysis ,Humans ,Clinical microbiology ,Saliva ,lcsh:Science ,Bifidobacterium ,Mouth ,Multidisciplinary ,biology ,Transmission (medicine) ,Comparative genomics ,lcsh:R ,Infant, Newborn ,Infant ,food and beverages ,Sequence Analysis, DNA ,Ribosomal RNA ,biology.organism_classification ,Gastrointestinal Microbiome ,Gastrointestinal Tract ,Bifidobacteriaceae ,030104 developmental biology ,Oral fluid ,Female ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Bifidobacteria are one of the most abundant bacterial groups in the infant gut microbiota and are closely associated with infant health and can potentially affect health in later life. However, the details regarding the source of bifidobacteria have yet to be completely elucidated. This study aimed to assess neonatal oral fluid (OF) as a transmission route for bifidobacteria to the infant gut during delivery. Neonatal OF and infant feces (IF) were collected immediately and one month after birth from 15 healthy vaginally delivered newborns. Bifidobacterium strains were isolated from OF and IF samples, and the similarity of strains between the OF-IF pairs was evaluated based on the average nucleotide identity (ANI) value. The 16S rRNA gene sequencing results revealed the presence of Bifidobacteriaceae at >1% relative abundance in all OF samples. Bifidobacterium strains were isolated from OF (9/15) and IF (11/15) samples, and those sharing high genomic homology (ANI values >99.5%) between the neonatal OF and IF samples were present in one-third of the OF-IF pairs. The results of this study indicate that viable bifidobacteria are present in neonatal OF and that OF at birth is a possible transmission route of bifidobacteria to the infant gut.
- Published
- 2019
20. Ultrasonographic study of intestinal Doppler blood flow in infantile non-IgE-mediated gastrointestinal food allergy
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Nobuyoshi Asai, Keisuke Jimbo, Kenji Hosoi, Yoshikazu Ohtsuka, Yo Aoyagi, Toshiaki Shimizu, Reiko Kyoudo, Nobuyasu Arai, Takahiro Kudo, and Tatsuo Kono
- Subjects
lcsh:Immunologic diseases. Allergy ,Male ,0301 basic medicine ,medicine.medical_specialty ,Milk allergy ,Ileum ,Gastroenterology ,Jejunum ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Eosinophilia ,Oral food challenge ,business.industry ,Infant, Newborn ,Infant ,Ultrasonography, Doppler ,General Medicine ,Immunoglobulin E ,Eosinophil ,medicine.disease ,Small intestine ,Intestines ,Diarrhea ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Regional Blood Flow ,Female ,Milk Hypersensitivity ,medicine.symptom ,lcsh:RC581-607 ,business - Abstract
Background: Although non-IgE-mediated gastrointestinal food allergy has increased rapidly in Japan, a small number of reports has evaluated B-mode and Doppler ultrasonographic findings in the acute phase of infantile gastrointestinal milk allergy. The aim of the present study was to compare the diagnostic utility of ultrasonographic findings and laboratory allergic data in non-IgE-mediated infantile gastrointestinal milk allergy. Methods: Sixteen cases of active non-IgE-mediated infantile gastrointestinal milk allergy, diagnosed by food elimination tests and oral food challenge tests (OFCTs) (group A), 15 cases of acute viral gastroenteritis (AGE) (group B), and 15 controls (group C) were enrolled. 1) B-mode abdominal ultrasound findings, 2) laboratory allergic data including eosinophil counts (Eos), serum IgE, and the antigen-specific lymphocyte proliferation test (ALPT) against milk protein, and 3) vessel density (VD) indirectly quantified by gastrointestinal Doppler flow at jejunum, ileum, and sigmoid colonic mucosae were evaluated and compared among the groups. Results: In the small intestine, wall thickening, dilation, mesenteric thickening, and poor peristalsis were found in 100%, 62.5%, 93.7%, and 100%, respectively, in group A. Eos, IgE, ALPT, and VD were positive in 25.0%, 0%, 87.5%, and 100%, respectively, in group A. Small intestinal VD was significantly greater in group A than in groups B (jejunum p
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- 2019
21. Clinical Safety and Utility of Pediatric Balloon-assisted Enteroscopy: A Multicenter Prospective Study in Japan
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Takahiro Kudo, Shuichiro Umetsu, Maiko Tatsuki, Shin-ichiro Hagiwara, Koji Yokoyama, Mikihiro Inoue, Toshiaki Shimizu, Yoshiko Nakayama, Toshifumi Yodoshi, Itaru Iwama, and Fumihiko Kakuta
- Subjects
Male ,Enteroscopy ,medicine.medical_specialty ,Adolescent ,Referral ,Operative Time ,MEDLINE ,03 medical and health sciences ,0302 clinical medicine ,Balloon assisted enteroscopy ,Japan ,030225 pediatrics ,Intestine, Small ,Humans ,Medicine ,Prospective Studies ,Single institution ,Child ,Prospective cohort study ,Double-Balloon Enteroscopy ,business.industry ,General surgery ,Gastroenterology ,Infant ,Single-Balloon Enteroscopy ,Intestinal Diseases ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Clinical safety ,Female ,030211 gastroenterology & hepatology ,Observational study ,business - Abstract
The benefit of balloon-assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan.This was a prospective, multi-institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double-balloon or single-balloon enteroscopy. Data were collected prospectively using a standardized questionnaire.We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1-17 years). Antegrade (oral-route) BAE was performed in 20 procedures (lowest body weight 12.9 kg, youngest age 3.7 years), and retrograde (anal-route) BAE in 76 (lowest body weight 10.8 kg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double-balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral-route BAE for diagnosis was significantly longer than anal-route for diagnosis (P 0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE.This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.
- Published
- 2019
22. Universal Recommendations for the Management of Acute Diarrhea in Nonmalnourished Children
- Author
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Bhupinder Sandhu, James A. Berkley, Eduardo Salazar-Lindo, Ilaria Liguoro, Sylvia Cruchet, Jorge Amil Dias, Mitchell B. Cohen, Alfredo Guarino, Andrea Lo Vecchio, Chris Boey, Philip M. Sherman, Toshiaki Shimizu, Dario Bruzzese, Guarino, Alfredo, Lo Vecchio, Andrea, Dias, Jorge Amil, Berkley, James A, Boey, Chri, Bruzzese, Dario, Cohen, Mitchell B, Cruchet, Sylvia, Liguoro, Ilaria, Salazar-Lindo, Eduardo, Sandhu, Bhupinder, Sherman, Philip M, and Shimizu, Toshiaki
- Subjects
recommendation ,Diarrhea ,Male ,Acute diarrhea ,medicine.medical_specialty ,Adolescent ,purl.org/pe-repo/ocde/ford#3.03.04 [https] ,diarrhea ,MEDLINE ,Psychological intervention ,Guidelines ,Pediatrics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Consistency (negotiation) ,children ,Clinical Protocols ,Medical ,030225 pediatrics ,Humans ,Medicine ,guidelines ,030212 general & internal medicine ,Preschool ,Child ,Intensive care medicine ,Children ,Societies, Medical ,purl.org/pe-repo/ocde/ford#3.02.03 [https] ,purl.org/pe-repo/ocde/ford#3.02.19 [https] ,business.industry ,Infant, Newborn ,Gastroenterology ,Infant ,Recommendation ,Acute gastroenteritis ,Newborn ,Gastroenteritis ,Clinical Practice ,Child, Preschool ,Acute Disease ,Practice Guidelines as Topic ,Pediatrics, Perinatology and Child Health ,Female ,Societies ,business ,gastroenteritis - Abstract
Objective: Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical interventions persist in both developing and developed countries. The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide. Methods: The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations. Results: A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%–96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%–95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended. Conclusions: Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners’ compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs.
- Published
- 2018
23. Efficacy and safety of adalimumab in paediatric patients with moderate-to-severe ulcerative colitis (ENVISION I): a randomised, controlled, phase 3 study
- Author
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Dan Turner, Mary Venetucci, Tricia Finney-Hayward, Frank M. Ruemmele, Andreas Lazar, Nicholas M. Croft, Mareike Bereswill, Toshiaki Shimizu, Nael M. Mostafa, Subra Kugathasan, Jaroslaw Kierkus, William A. Faubion, and Yuri Sanchez Gonzalez
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Population ,Anti-Inflammatory Agents ,Phases of clinical research ,Placebo ,Severity of Illness Index ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Severity of illness ,medicine ,Adalimumab ,Humans ,education ,Child ,education.field_of_study ,Hepatology ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Gastroenterology ,medicine.disease ,Ulcerative colitis ,Clinical trial ,Treatment Outcome ,030220 oncology & carcinogenesis ,Child, Preschool ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,Female ,business ,medicine.drug - Abstract
Biologic treatment options are limited for children with ulcerative colitis. The aim of this study was to assess the safety and efficacy of adalimumab in children with moderate-to-severe ulcerative colitis.The double-blind ENVISION I study was done at 24 hospitals in ten countries. Children (4-17 years) with moderate-to-severe ulcerative colitis despite stable doses of concurrent treatment with oral corticosteroids or immunosuppressants were enrolled. Per the original study design, patients were randomly assigned with an Interactive Voice Response System (IVRS) to receive either high-dose induction adalimumab (2·4 mg/kg [maximum 160 mg] at weeks 0 and 1) or standard-dose induction adalimumab (2·4 mg/kg at week 0 and placebo at week 1); both groups received 1·2 mg/kg (maximum 80 mg) at week 2 and 0·6 mg/kg (maximum 40 mg) at weeks 4 and 6. Patients with partial Mayo score (PMS) response at week 8 (defined as a decrease of two or more points and a decrease of ≥30% from baseline in PMS) were randomly assigned (2:2:1)-using IVRS-to receive either high-dose maintenance adalimumab (0·6 mg/kg weekly), standard-dose maintenance adalimumab (0·6 mg/kg every other week), or placebo up to week 52 (random assignment to the placebo group was ceased mid-trial, as was randomisation in the induction phase with all subsequent patients receiving open-label high-dose induction adalimumab). Coprimary endpoints were the proportion of patients with PMS remission at week 8 (intent-to-treat [ITT]-E population, not including those patients who were not randomised in the induction phase) and full Mayo score (FMS) remission at week 52 in week 8 PMS responders (maintenance ITT-E [mITT-E] population), for which the pooled adalimumab group (patients who received high-dose or standard-dose adalimumab) and the individual dose groups were compared against external adult placebo rates. We report results of the final confirmatory analysis. This trial is registered with ClinicalTrials.gov, NCT02065557.93 children were recruited between Oct 13, 2014, and Sept 5, 2018, to the main study (77 [83%] were randomly assigned [double-blind] to receive high-dose or standard-dose induction adalimumab; 16 [17%] received open-label high-dose induction adalimumab after study design change). At week 8, 74 (80%) children who were PMS responders continued to the maintenance period. 62 (84%) patients were randomly assigned to receive high-dose or standard-dose maintenance adalimumab treatment; 12 (16%) patients received placebo. In patients in the ITT-E population who were randomly assigned to receive high-dose induction adalimumab, a significantly higher proportion of patients were in PMS remission at week 8 (28 [60%] of 47) compared with external placebo (19·8%; p=0·0001). 13 (43%) of 30 patients in the standard-dose induction adalimumab group were in PMS remission at week 8 versus an external placebo rate of 19·8%, but this difference was not significant (p=0·38). Similarly, FMS remission at week 52 in children who were week 8 PMS responders was reported in a significantly higher proportion of patients in mITT-E population who received high-dose maintenance adalimumab (14 [45%] of 31 patients) versus external placebo at week 52 (18·4%; p=0·0001). Nine (29%) of 31 patients in the standard-dose maintenance adalimumab group were in FMS remission at week 52 versus an external placebo rate of 18·4%, but this difference was not significant (p=0·38). Remission rates in the pooled adalimumab groups were significantly better compared with external placebo (PMS remission at week 8: 41 [53%] of 77 patients; p0·0001; FMS remission at week 52: 23 [37%] of 62 patients; p=0·0001). 21 (23%) of 93 patients in the main study had one or more treatment-emergent serious adverse events during any adalimumab exposure. The most common adverse events were headache, anaemia, and ulcerative colitis flare during the induction period and ulcerative colitis flare, headache, and nasopharyngitis during the maintenance period.Clinically meaningful rates of remission and response were reported in children who received adalimumab in this study. No new safety signals were observed, suggesting that adalimumab is an efficacious and safe treatment option for children with moderate-to-severe ulcerative colitis.AbbVie.
- Published
- 2021
24. Approach to the Seamless Management of Inflammatory Bowel Disease, Considering Special Situations, Shared Decision-Making, and Disease Burden
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Toshiaki Shimizu and Nobuo Aoyama
- Subjects
Adult ,medicine.medical_specialty ,Medical staff ,Disease ,Review ,Inflammatory bowel disease ,Biological drugs ,Cost of Illness ,Pregnancy ,medicine ,Humans ,Transitional care ,Intensive care medicine ,Disease burden ,Aged ,Thiopurine methyltransferase ,biology ,business.industry ,Gastroenterology ,medicine.disease ,Colitis ,Inflammatory Bowel Diseases ,Cross-Sectional Studies ,biology.protein ,Total care ,Female ,business - Abstract
Background: While the number of inflammatory bowel disease (IBD) patients has been steadily increasing, a lot of effective treatments have become available, including biological drugs. However, there still exists no effective treatment universally for all types of IBD patients. We have continuously discussed “Total Care” for IBD patients in the 3 consecutive annual meetings of the Japanese Gastroenterological Association from the 14th meeting to the 16th meeting in 2018–2020. Summary: In the 14th meeting, we summarized cross-sectional issues under the title “From Total Care to Microbiota” as for their subthemes. In the 15th meeting, under the title of “Consensus and Pitfalls in Special Situations,” we discussed the thiopurine treatment for the patients in their childhood or pregnancy and lactation period as well as the cytapheresis treatment for elderly patients. In the 16th meeting, under the title “Future Issues in Special Situations: Including Disease Burden,” we discussed about the issues in childhood-onset IBD, including transitional care and the new option of combination of treatments in their adulthood and their disease burdens. Key Messages: “Total Care” for IBD patients should be considered from a broad perspective with shared decision-making. It is imperative to involve medical staff members for careful handling of a wide range of disease burdens.
- Published
- 2020
25. A novel mutation in the SLCO2A1 gene, encoding a prostaglandin transporter, induces chronic enteropathy
- Author
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Keisuke Jimbo, Toshiaki Okuno, Ryuichi Ohgaki, Kou Nishikubo, Yuri Kitamura, Yumiko Sakurai, Lili Quan, Hiromichi Shoji, Yoshikatsu Kanai, Toshiaki Shimizu, and Takehiko Yokomizo
- Subjects
0301 basic medicine ,Male ,Prostaglandin ,Gene Identification and Analysis ,Organic Anion Transporters ,Capsule Endoscopy ,Biochemistry ,0302 clinical medicine ,Immunofluorescence Staining ,Medicine and Health Sciences ,Metabolites ,Lipid Hormones ,Child ,Ulcers ,Staining ,Multidisciplinary ,Animal Models ,Pedigree ,Experimental Organism Systems ,Medicine ,Cell lines ,Female ,Biological cultures ,Research Article ,Heterozygote ,Science ,Mouse Models ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Cell Line ,03 medical and health sciences ,Model Organisms ,Signs and Symptoms ,Protein Domains ,Genetics ,Humans ,Stomach Ulcer ,Mutation Detection ,Cell Membrane ,HEK 293 cells ,Correction ,Biology and Life Sciences ,Endoscopy ,Hormones ,030104 developmental biology ,Metabolism ,Specimen Preparation and Treatment ,Mutation ,Prostaglandins ,Animal Studies ,Clinical Medicine ,030217 neurology & neurosurgery - Abstract
Chronic enteropathy associated withSLCO2A1gene (CEAS) is caused by loss-of-function mutations inSLCO2A1, which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of theSLCO2A1gene. Compound heterozygous variants inSLCO2A1were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE2, while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant ofSLCO2A1that caused loss-of-function and induced CEAS.
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- 2020
26. Exercise echocardiography demonstrates potential myocardial damage in patients with repaired tetralogy of Fallot using layer-specific strain analysis
- Author
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Katsumi Akimoto, Toshiaki Shimizu, Kotoko Matsui, Sachie Shigemitsu, Mariko Yamada, Satoshi Akimoto, Shiori Kawasaki, Ken Takahashi, Keisuke Nakanishi, Takeshi Iso, Maki Kobayashi, Masahiko Kishiro, and Kana Yazaki
- Subjects
Adult ,Male ,medicine.medical_specialty ,Supine position ,Adolescent ,Rest ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Ventricular Dysfunction, Left ,Young Adult ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,Circumferential strain ,Humans ,In patient ,030212 general & internal medicine ,Exercise ,Endocardium ,Tetralogy of Fallot ,Subclinical infection ,business.industry ,Myocardium ,General Medicine ,medicine.disease ,Exercise echocardiography ,Echocardiography ,Case-Control Studies ,Pediatrics, Perinatology and Child Health ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction:Exercise stress echocardiography and layer-specific strains are emerging as important tools for cardiac assessment. This study was aimed to evaluate layer-specific strains and torsion parameters during exercise in order to investigate the characteristics of cardiac dysfunction in patients with repaired tetralogy of Fallot and to detect subclinical left ventricular dysfunction.Materials and Methods:Thirteen patients with repaired tetralogy of Fallot (median age, 17.3 [interquartile range, 14.5–22.9] years; 6 males) and 13 controls (median age, 28.5 [interquartile range, 27.6–31.6] years; 13 males) underwent echocardiography at rest and during supine exercise. Layer-specific longitudinal strain and circumferential strain of three myocardial layers (endocardium, midmyocardium, and epicardium), torsion, and untwisting rate were measured using two-dimensional speckle-tracking echocardiography.Results:Peak endocardial papillary circumferential strain (−21.1 ± 2.6% vs. −25.8 ± 3.8%, p = 0.007), midmyocardial apical circumferential strain (−11.1 ± 4.0% vs. −15.6 ± 3.2%, p = 0.001), epicardial apical circumferential strain (−11.1 ± 4.0% vs. −15.6 ± 3.2%, p = 0.021), and torsion (8.9 ± 6.0 vs. 14.9 ± 4.8 degree, p = 0.021) were significantly lower in the repaired tetralogy of Fallot group than in the control group during exercise, though no significant difference was found between patients and controls at rest.Conclusions:Analysis of layer-specific strains and torsion parameters during exercise could detect subclinical left ventricular dysfunction in patients with repaired tetralogy of Fallot, which might reflect potential myocardial damage, at a stage where these parameters have normal values at rest. This finding provides new insight into the mechanisms of cardiac dysfunction in patients with repaired tetralogy of Fallot.
- Published
- 2020
27. Changes in conjugated urinary bile acids across age groups
- Author
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Hiroshi Nittono, Takao Kurosawa, Keiko Sato, Genta Kakiyama, Mitsuyoshi Suzuki, Hiroaki Sato, Akihiko Kimura, Toshiaki Shimizu, Hajime Takei, William M. Pandak, Tsuyoshi Murai, and Nakayuki Naritaka
- Subjects
Adult ,Male ,medicine.medical_specialty ,Taurine ,Spectrometry, Mass, Electrospray Ionization ,Adolescent ,medicine.drug_class ,Urinary system ,Clinical Biochemistry ,030209 endocrinology & metabolism ,digestive system ,Biochemistry ,Bile Acids and Salts ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Endocrinology ,Cholestasis ,Liquid chromatography–mass spectrometry ,Tandem Mass Spectrometry ,Internal medicine ,Bile acid conjugation ,medicine ,Humans ,Child ,Molecular Biology ,Pharmacology ,Fetus ,Bile acid ,Organic Chemistry ,Infant, Newborn ,Infant ,Reproducibility of Results ,Middle Aged ,Reference Standards ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,Child, Preschool ,Glycine ,Female ,Chromatography, Liquid - Abstract
Bile acid compositions are known to change dramatically after birth with aging. However, no reports have described the transition of conjugated urinary bile acids from the neonatal period to adulthood, and such findings would noninvasively offer insights into hepatic function. The aim of this study was to investigate differences in bile acid species, conjugation rates, and patterns, and to pool characteristics for age groups. We measured urinary bile acids in spot urine samples from 92 healthy individuals ranging from birth to 58 years old using liquid chromatography tandem mass spectrometry (LC/ESI-MS/MS). Sixty-six unconjugated and conjugated bile acids were systematically determined. After birth, urinary bile acids dramatically changed from fetal (i.e., Δ4-, Δ5-, and polyhydroxy-bile acids) to mature (i.e., CA and CDCA) bile acids. Peak bile acid excretion was 6–8 days after birth, steadily decreasing thereafter. A major change in bile acid conjugation pattern (taurine to glycine) also occurred at 2–4 months old. Our data provide important information regarding transitions of bile acid biosynthesis, including conjugation. The data also support the existence of physiologic cholestasis in the neonatal period and the establishment of the intestinal bacterial flora in infants.
- Published
- 2020
28. Very early-onset inflammatory bowel disease in Japan: A nationwide survey
- Author
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Takahiro Kudo, Hitoshi Tajiri, Keiichi Uchida, Katsuhiro Arai, Ryota Hokari, Toshiaki Shimizu, and Yasuo Suzuki
- Subjects
Male ,medicine.medical_specialty ,Colonoscopy ,Disease ,Nationwide survey ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Surveys and Questionnaires ,Epidemiology ,Intestine, Small ,Medicine ,Humans ,Endoscopy, Digestive System ,Medical diagnosis ,Age of Onset ,Child ,Retrospective Studies ,Hepatology ,medicine.diagnostic_test ,business.industry ,Esophagogastroduodenoscopy ,Gastroenterology ,medicine.disease ,Inflammatory Bowel Diseases ,030220 oncology & carcinogenesis ,Primary immunodeficiency ,030211 gastroenterology & hepatology ,Female ,business - Abstract
Background and aim Very early-onset inflammatory bowel disease is defined as inflammatory bowel disease diagnosed before 6 years of age. Very early-onset inflammatory bowel disease has various differential diagnoses, including primary immunodeficiency disorders, and is known to be resistant to conventional treatment. Therefore, global attention is required to manage this challenging condition. We conducted a retrospective epidemiological survey of the number of patients, final diagnosis, and examinations performed to diagnose very early-onset inflammatory bowel disease in Japan. Methods A primary questionnaire about the number of very early-onset bowel disease cases and its diagnosis was administered to 630 pediatric facilities nationwide in Japan. A secondary survey about the examinations performed to achieve diagnosis was sent to the facilities that responded to the first survey. Results The answering rate was 92.2% (581/630 facilities); 81 facilities had 225 very early-onset bowel disease patients undergoing their care during the past 68 months. Twenty-six patients (11.6%) were diagnosed with immunodeficiency-associated inflammatory bowel disease. The answering rate of the secondary survey was 70.4% (57/81 facilities). Colonoscopy, esophagogastroduodenoscopy, and small bowel imaging were performed for 99.4%, 67.5%, and 28.8% of patients, respectively. Genetic analysis was performed for 26.9% (43/160 patients) of patients, and 51.2% (22/43) of patients were diagnosed with immunodeficiency-associated inflammatory bowel disease. Conclusions Approximately 40 patients are diagnosed yearly in Japan. Imaging studies, especially for small bowel lesions, can be challenging for this unique group of patients. However, a comprehensive approach including immunological and genetic analyses appears useful for diagnosing immunodeficiency-associated inflammatory bowel disease.
- Published
- 2020
29. Exploring Traits of Autism and Their Impact on Functional Disability in Children with Somatic Symptom Disorder
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Toshiaki Shimizu, Mariko Hosozawa, Kyoko Tanaka, and Kyoko Hatta
- Subjects
Male ,Autism-spectrum quotient ,Adolescent ,Somatic symptom disorder ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Surveys and Questionnaires ,Developmental and Educational Psychology ,medicine ,Humans ,Attention ,0501 psychology and cognitive sciences ,Autistic Disorder ,Child ,Somatoform Disorders ,Subclinical infection ,05 social sciences ,medicine.disease ,Disabled Children ,Medically Unexplained Symptoms ,Phenotype ,Functional disability ,Autism spectrum disorder ,Autism ,Female ,Psychology ,030217 neurology & neurosurgery ,050104 developmental & child psychology ,Clinical psychology - Abstract
Subclinical traits of autism were measured in children with somatic symptom disorder (SSD, n = 28) and compared with age-matched controls (n = 26) using the Autism Spectrum Quotient (AQ) children’s version. The KINDLR quality of life questionnaire was used to assess functional disability. Although there was no significant group difference in total traits of autism, SSD group had significantly greater difficulty in attention switching domain. Logistic regression analysis confirmed attention switching and age were associated with increased likelihood of SSD. In SSD group, difficulty in attention switching significantly negatively correlated with total, family, and friends quality of life scores. In conclusion, assessment and treatment targeting difficulties in attention switching could be useful when dealing with children with SSD.
- Published
- 2018
30. Positive effects of single-daily high-dose mizoribine therapy after cyclophosphamide in young children with steroid-dependent nephrotic syndrome
- Author
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Shuichiro Fujinaga, Daishi Hirano, Akira Mizutani, Toshiaki Shimizu, and Koji Sakuraya
- Subjects
Male ,Nephrology ,medicine.medical_specialty ,Nephrotic Syndrome ,Time Factors ,Adolescent ,Cyclophosphamide ,Physiology ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Group A ,Drug Administration Schedule ,Group B ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Physiology (medical) ,Internal medicine ,Humans ,Medicine ,Age of Onset ,Child ,Retrospective Studies ,Mizoribine ,business.industry ,Remission Induction ,Steroid-dependent nephrotic syndrome ,Mean age ,medicine.disease ,Treatment Outcome ,Child, Preschool ,Female ,Steroids ,Ribonucleosides ,business ,human activities ,Nephrotic syndrome ,Immunosuppressive Agents ,medicine.drug - Abstract
Mizoribine (MZR) therapy after cyclophosphamide (CPM) therapy may be an attractive option in patients with steroid-dependent nephrotic syndrome (SDNS) for the purpose of maintaining remission. This is because CPM is administered only once due to its severe side effects such as gonadal toxicity. However, the long-term prognosis after the treatment regimen remains unknown.We retrospectively analyzed the clinical course (median follow-up, 5.9 years) of 54 young children with SDNS (43 boys; age 10 years) who had undergone 12-week CPM therapy. The patients were classified into two groups: group A, undergoing MZR therapy for 12 months for maintaining remission after CPM therapy (N = 36), and group B, undergoing CPM monotherapy (N = 18).For 2 years after CPM therapy, 21 of the 36 group A patients were in sustained remission, whereas only 4 of the 18 group B patients had maintained remission (58% vs. 22%, p 0.05). Furthermore, the rate of regression to SDNS after CPM was significantly lower in group A than in group B (6% vs. 39%, p 0.05). At the last follow-up (mean age, 10.9 years), 27 of the 36 group A patients (75%) had not received any steroid-sparing agent after the treatment regimen.Single daily high-dose MZR therapy after CPM therapy may have positive outcomes in young children with SDNS in the long term.
- Published
- 2018
31. Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis
- Author
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Kazuhiko Bessho, Hiroyuki Kusuhara, Atsuko Nakazawa, Hironori Kusano, Ayano Inui, Saeko Hirai, Satoshi Nakano, Hisamitsu Hayashi, Kei Minowa, Satoshi Watanabe, Masayoshi Kage, Yusuke Sabu, Yoh Zen, Yoshihiro Azuma, Toshiaki Shimizu, Shuhei Osaka, Hiroki Kondou, Ken Tanikawa, Hidefumi Nakamura, Takeshi Kimura, and Mitsuyoshi Suzuki
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,lcsh:Medicine ,Antineoplastic Agents ,Cholestasis, Intrahepatic ,Paediatric research ,Gastroenterology ,Phenylbutyrate ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Oral administration ,Internal medicine ,medicine ,Humans ,Tissue Distribution ,Adverse effect ,lcsh:Science ,Child ,Liver diseases ,ATP Binding Cassette Transporter, Subfamily B, Member 11 ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,lcsh:R ,Progressive familial intrahepatic cholestasis ,Infant ,Drug Synergism ,medicine.disease ,Prognosis ,Phenylbutyrates ,Diet ,Regimen ,030104 developmental biology ,Postprandial ,Child, Preschool ,Mutation ,030211 gastroenterology & hepatology ,lcsh:Q ,Female ,Clinical pharmacology ,Liver function tests ,business - Abstract
Progressive familial intrahepatic cholestasis (PFIC), a rare inherited disorder, progresses to liver failure in childhood. We have shown that sodium 4-phenylbutyrate (NaPB), a drug approved for urea cycle disorders (UCDs), has beneficial effects in PFIC. However, there is little evidence to determine an optimal regimen for NaPB therapy. Herein, a multicenter, open-label, single-dose study was performed to investigate the influence of meal timing on the pharmacokinetics of NaPB. NaPB (150 mg/kg) was administered orally 30 min before, just before, and just after breakfast following overnight fasting. Seven pediatric PFIC patients were enrolled and six completed the study. Compared with postprandial administration, an approved regimen for UCDs, preprandial administration significantly increased the peak plasma concentration and area under the plasma concentration-time curve of 4-phenylbutyrate by 2.5-fold (95% confidential interval (CI), 2.0–3.0;P = 0.003) and 2.4-fold (95% CI, 1.7–3.2;P = 0.005). The observational study over 3 years in two PFIC patients showed that preprandial, but not prandial or postprandial, oral treatment with 500 mg/kg/day NaPB improved liver function tests and clinical symptoms and suppressed the fibrosis progression. No adverse events were observed. Preprandial oral administration of NaPB was needed to maximize its potency in PFIC patients.
- Published
- 2019
32. Association between the frequency of bedwetting and late preterm birth in children aged ≥5 years
- Author
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Yuji Nishizaki, Naoto Nishizaki, Yoshiyuki Ohtomo, Toshiaki Shimizu, Noboru Yoshida, Masato Kantake, Naotake Yanagisawa, Kaoru Obinata, Shinichi Niijima, and Hiromichi Shoji
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Demographics ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Initial visit ,030225 pediatrics ,Late preterm ,Birth Weight ,Humans ,Medicine ,030212 general & internal medicine ,Child ,Retrospective Studies ,business.industry ,Maternal and child health ,Medical record ,Confounding ,Gestational age ,General Medicine ,Late Preterm Birth ,Pediatrics, Perinatology and Child Health ,Premature Birth ,Female ,business ,Nocturnal Enuresis - Abstract
AIM We examined the associations between late preterm (LPT) birth children aged ≥5 years and the frequency of bedwetting. Moreover, those who were born full-term/low birthweight (BW), LPT/low BW, LPT/normal BW and LPT/low BW were compared. METHODS In total, we evaluated 614 patients who underwent assessments for frequent bedwetting at the three hospitals from January 2014 to December 2016. Data at the initial visit were collected from the electronic medical records. We assessed the patients' bladder diaries and questionnaires containing detailed information on demographics and frequency of bedwetting per month. Neonatal data were collected from the Maternal and Child Health Handbook. RESULTS Frequency of bedwetting in the LPT/low BW group was higher than in the term/low BW group (28 vs. 22.5, p < 0.05). However, the frequency between the LPT/normal BW group and the LPT/low BW group was not significantly different (28 vs. 28, p = 1.00). Multiple regression analyses were conducted to eliminate potential confounding factors, attention-deficit/hyperactivity disorder and intellectual disability, but results were not changed. CONCLUSION This study revealed that LPT/low BW was associated with increased frequency of bedwetting in children. The results suggest that gestational age should be considered when examining patients with severe bedwetting.
- Published
- 2018
33. Choline-related metabolites influenced by feeding patterns in preterm and term infants
- Author
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Hiromichi Shoji, Naoko Kaga, Yoshiki Miura, Naho Ikeda, Hikari Taka, Toshiaki Shimizu, and Ken Hisata
- Subjects
Male ,0301 basic medicine ,Urinary system ,Breastfeeding ,Physiology ,Pilot Projects ,030209 endocrinology & metabolism ,Mass Spectrometry ,Choline ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Metabolome ,Humans ,Medicine ,Feeding patterns ,030109 nutrition & dietetics ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Feeding Behavior ,Infant Formula ,Bottle Feeding ,Term (time) ,Breast Feeding ,chemistry ,Infant formula ,Pediatrics, Perinatology and Child Health ,Female ,business ,Infant, Premature - Abstract
Objective: This study was performed to examine the choline status on term and preterm infants using urinary metabolome analysis.Material and methods: Samples were collected from 19 term and...
- Published
- 2018
34. Long-term renal tubular damage in intrauterine growth-restricted rats
- Author
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Hiromichi Shoji, Yayoi Murano, Naho Ikeda, Naoto Nishizaki, Taichi Hara, Toshiaki Shimizu, and Amane Endo
- Subjects
Male ,medicine.medical_specialty ,Urinary system ,030232 urology & nephrology ,Urology ,Intrauterine growth restriction ,Rats, Sprague-Dawley ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine.artery ,medicine ,Animals ,Renal Insufficiency ,030212 general & internal medicine ,Uterine artery ,Ligation ,reproductive and urinary physiology ,Fetal Growth Retardation ,biology ,business.industry ,Beta-2 microglobulin ,Sham surgery ,medicine.disease ,female genital diseases and pregnancy complications ,Rats ,Uterine Artery ,Kidney Tubules ,Cystatin C ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female ,business ,Biomarkers - Abstract
Background Intrauterine growth restriction (IUGR) has been shown to be associated with increased risk of renal disease or hypertension in later life. Glomerular dysfunction, however, has mainly been reported, and limited information is available to link IUGR with renal tubular damage. The aim of this study was therefore to investigate urinary markers of tubular damage in a rat model of IUGR induced by bilateral uterine artery ligation. Methods Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation, while the control group underwent sham surgery. Results Birthweight was reduced, and urinary β2-microglobulin (β2-MG)-, cystatin C (Cys-C)-, and calbindin-to-creatinine ratios were significantly higher at weeks 4 and 8 in the IUGR group compared with the control group. These urinary markers were not significantly different at week 16 between the two groups. Increased excretion of urinary β2-MG, Cys-C, and calbindin was observed in IUGR rats at ≥8 weeks of age. Conclusion Children born with IUGR are at increased risk for renal tubular damage.
- Published
- 2018
35. Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan
- Author
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Seiji Fukumoto, Keiichi Ozono, Koji Oba, Haruo Mizuno, Hirokazu Tsukahara, Hirofumi Nakayama, Keisuke Nagasaki, Satoshi Kusuda, Yosikazu Nakamura, Sachiko Kitanaka, Toshimi Michigami, Satomi Koyama, Yukihiro Hasegawa, Ikuma Fujiwara, Kenji Ihara, Noriyuki Takubo, Tohru Yorifuji, Kosei Hasegawa, Taichi Kitaoka, Toshiaki Shimizu, Yuko Sakamoto, Yusuke Tanahashi, and Takuo Kubota
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Population ,Breastfeeding ,030209 endocrinology & metabolism ,Rickets ,Nationwide survey ,vitamin D deficiency ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Japan ,Prevalence ,medicine ,Humans ,030212 general & internal medicine ,Vitamin D ,Child ,education ,education.field_of_study ,Hypocalcemia ,business.industry ,Incidence ,Public health ,Infant ,Vitamin D Deficiency ,medicine.disease ,Health Surveys ,Unbalanced diet ,Confidence interval ,Child, Preschool ,Female ,Symptom Assessment ,business - Abstract
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.
- Published
- 2018
36. In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With Childhood Cancer After Anthracycline Treatment Using Layer-Specific Strain Analysis
- Author
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Katsumi Akimoto, Masahiro Saito, Toshiaki Shimizu, Kana Yazaki, Maki Kobayashi, Hiroyuki Tamaichi, Ken Takahashi, Takeshi Iso, Mariko Yamada, Masaki Nii, Sachie Shigemitsu, and Junya Fujimura
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Heart Diseases ,Anthracycline ,Long Term Adverse Effects ,Strain (injury) ,030204 cardiovascular system & hematology ,Young Adult ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,Neoplasms ,Internal medicine ,Humans ,Medicine ,Anthracyclines ,Survivors ,030212 general & internal medicine ,Young adult ,Child ,Endocardium ,Cardiotoxicity ,Ejection fraction ,business.industry ,Age Factors ,Case-control study ,General Medicine ,medicine.disease ,Echocardiography ,Case-Control Studies ,Disease Progression ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Anthracycline cardiotoxicity affects clinical outcomes, and its early detection using methods that rely on conventional echocardiography, such as left ventricular ejection fraction (LVEF) is difficult. This study aimed to evaluate the characteristics and the differences in cardiac dysfunction among childhood cancer survivors in 3 age groups using layer-specific strain analysis in a wide age range.Methods and Results:The 56 patients (median age: 15 [range: 6.8-40.2] years) who had been treated with anthracycline for childhood cancer were divided into 3 age groups (C1: 6-12 years, C2: 13-19 years, C3: 20-40 years) after anthracycline treatment, and 72 controls of similar ages were divided into 3 corresponding groups (N1, N2, and N3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Myocardial damage had not occurred yet in C1. Endocardial CS at the basal level was less in C2 than in N2. Endocardial CS at all levels and midmyocardial CS at the basal and papillary levels were lower in C3 than in N3. LVEF and LS were not significantly different between patients and controls. Conclusions Among survivors of childhood cancer, impaired myocardial deformation starts in adolescence and extends from the endocardium towards the epicardium and from the base towards the apex with age. These findings are a novel insight into the time course of anthracycline cardiotoxicity.
- Published
- 2018
37. Urinary angiotensinogen in pediatric urinary tract infection
- Author
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Akihiro Nakao, Hiromichi Shoji, Yumiko Sakurai, Akira Mizutani, Kuniyoshi Hayashi, Toshiaki Shimizu, Nao Miyazaki, Reina Mayumi, Yayoi Murano, Tomoyuki Nakazawa, Taichi Hara, and Reina Yokota
- Subjects
Male ,medicine.medical_specialty ,Urinary system ,Angiotensinogen ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Renal injury ,030225 pediatrics ,Internal medicine ,parasitic diseases ,medicine ,Humans ,In patient ,Prospective Studies ,business.industry ,Infant, Newborn ,Infant ,bacterial infections and mycoses ,female genital diseases and pregnancy complications ,Urinary Tract Infections ,Pediatrics, Perinatology and Child Health ,Biomarker (medicine) ,Female ,business ,Biomarkers - Abstract
BACKGROUND Urinary tract infection (UTI) is one of the most common diseases in children, and urinary angiotensinogen (U-AGT) is a new biomarker gathering attention in many renal diseases. U-AGT reflects intrarenal renin-angiotensin system (RAS) activity. We conducted a study to measure U-AGT in children
- Published
- 2019
38. Analysis of Factors Associated With Body Mass Index at Ages 18 and 36 Months Among Infants Born Extremely Preterm
- Author
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Hiromichi Shoji, Masato Kantake, Yayoi Murano, Toshiaki Shimizu, Natsuki Okawa, Naho Morisaki, Stuart Gilmour, Naho Ikeda, and Kuniyoshi Hayashi
- Subjects
Male ,medicine.medical_specialty ,Birth weight ,Intrauterine growth restriction ,Pediatrics ,Body Mass Index ,Cohort Studies ,Japan ,medicine ,Humans ,Neonatology ,Original Investigation ,Retrospective Studies ,Pregnancy ,business.industry ,Obstetrics ,Research ,Infant ,Gestational age ,General Medicine ,medicine.disease ,Online Only ,Child, Preschool ,Infant, Extremely Premature ,Gestation ,Body-Weight Trajectory ,Female ,business ,Body mass index ,Cohort study - Abstract
This cohort study investigates factors associated with body mass index in the first 36 months of life among infants born extremely preterm., Key Points Question What factors are associated with body mass index (BMI) in the first 36 months of life among infants born at gestational age less than 28 weeks? Findings In this cohort study of 8838 infants born extremely preterm, intrauterine growth restriction (IUGR) was associated with decreased BMI and BMI z score and older gestational age was associated with increased BMI and BMI z score at ages 18 months and 36 months among infants born in single pregnancies. In multiple pregnancies, IUGR was associated with decreased BMI z score at age 36 months, but the difference in scores was smaller. Meaning This study found that among infants born extremely preterm, gestational age and the presence of IUGR were associated with subsequent BMI., Importance The development of neonatology has been associated with improved survival among infants born extremely preterm, and understanding their long-term outcomes is becoming increasingly important. However, there is little information on body mass index (BMI) among these children. Objective To determine factors associated with BMI at ages 18 months and 36 months among infants born extremely preterm. Design, Setting, and Participants This retrospective, multicenter cohort study was conducted using data from the Neonatal Research Network Japan database for 8838 infants born at gestational ages 23 to 28 weeks with data on BMI at 18 months and 36 months. Data were analyzed from April 2018 through June 2021. Exposures BMI and BMI z score at ages 18 months and 36 months were regressed with gestational age, intrauterine growth restriction (IUGR) status, and complications during pregnancy and the neonatal period separately by presence of multiple pregnancy and sex. Main Outcomes and Measures BMI and BMI z score at ages 18 months and 36 months. Results Among 16 791 eligible infants born extremely preterm, 8838 infants were included in the analysis. There were 7089 infants born from single pregnancies (mean [SD] gestational age, 26.0 [1.6] weeks; 3769 [53.2%] boys; mean [SD] birth weight, 847 [228] g) and 1749 infants born from multiple pregnancies (mean [SD] gestational age, 26.3 [1.5] weeks; 903 [51.6%] boys; mean [SD] birth weight, 860 [217] g). In single pregnancies, every week of increased gestational age was associated with an increase in BMI of 0.21 (95% CI, 0.17-0.25) among boys and 0.20 (95% CI, 0.15-0.25) among girls at age 18 months and 0.21 (95% CI, 0.18-0.24) among boys and 0.21 (95% CI, 0.18-0.24) among girls at age 36 months. There was an interaction association between gestational age and IUGR among boys at age 36 months, with a decrease in the change associated with gestational age of 0.12 (95% CI, 0.05-0.19). Every week of increased gestational age in single pregnancies was associated with an increase in BMI z score of 0.14 (95% CI, 0.17-0.21) among boys and 0.17 (95% CI, 0.13-0.21) among girls at age 18 months and 0.19 (95% CI, 0.16-0.22) among boys and 0.17 (95% CI, 0.15-0.20) among girls at age 36 months. Among single pregnancies, IUGR was associated with a decrease in BMI among boys (0.59 [95% CI, 0.23-0.95]) and girls (0.75 [95% CI, 0.39-1.11]) and BMI z score among boys 0.85 [95% CI, 0.25-0.95)] and girls (0.67 [95% CI, 0.36-0.97] at age 18 months and BMI among boys (0.44 [95% CI, 0.17-0.18]) and girls (0.84 [95% CI, 0.55-1.12]) and BMI z score among boys (0.46 [95% CI, 0.21-0.71]) and girls (0.77 [95% CI, 0.53-1.01]) at age 36 months. In multiple pregnancies, IUGR was associated with a decrease in BMI z score at age 36 months among boys (0.26 [95% CI, 0.42-0.89]) and girls (0.29 [95% CI, 0.22-0.79]). In single pregnancies intraventricular hemorrhage (IVH) was associated with a decrease in BMI of 0.47 (95% CI, 0.21-0.73) among boys and 0.42 (95% CI, 0.13-0.71) among girls at age 18 months and 0.53 (95% CI, 0.32-0.74) among boys and 0.31 (95% CI, 0.07-0.54) among girls at age 36 months. IVH was associated with a decrease in BMI z score in single pregnancies of 0.63 (95% CI, 0.20-0.41) among boys and 0.35 (95% CI, 0.12-0.60) among girls at age 18 months and 0.53 (95% CI, 0.34-0.71) among boys and 0.30 (95% CI, 0.11-0.50) among girls at age 36 months. Similar associations were seen in multiple pregnancies. Conclusions and Relevance This study found that gestational age, the presence of IUGR and multiple pregnancy, and IVH complications were associated with infant BMI at ages 18 months and 36 months. These findings suggest that these complicating factors should be considered when setting growth targets and nutrition strategies for infants born extremely preterm.
- Published
- 2021
39. Association of zinc and copper with clinical parameters in the preterm newborn
- Author
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Ken Hisata, Chiharu Kojima, Naho Ikeda, Hiromichi Shoji, Tomohiro Kitamura, and Toshiaki Shimizu
- Subjects
Adult ,Male ,Brain development ,Intrauterine growth restriction ,chemistry.chemical_element ,Physiology ,Gestational Age ,Zinc ,Anthropometric parameters ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Fetal growth ,Humans ,Medicine ,Retrospective Studies ,Fetal Growth Retardation ,Anthropometry ,business.industry ,Infant, Newborn ,Gestational age ,Middle Aged ,medicine.disease ,chemistry ,Pediatrics, Perinatology and Child Health ,Female ,Stepwise multiple regression analysis ,business ,Copper ,Infant, Premature ,030217 neurology & neurosurgery - Abstract
BACKGROUND Given that preterm infants are born at a time of rapid fetal growth, they are at risk of deficiency of essential nutrients for brain development, including zinc (Zn) and copper (Cu). This study evaluate the relationship between serum Cu or Zn, gestational age (GA) and anthropometric parameters at birth in preterm infants. METHODS This was a retrospective study of infants
- Published
- 2017
40. Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic Nocturnal Enuresis
- Author
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Toshiaki Shimizu, Amane Endo, Yoshiyuki Ohtomo, Masato Yasui, Taichi Hara, and Shinichi Niijima
- Subjects
Male ,Vasopressin ,medicine.medical_specialty ,Urology ,Urinary system ,030232 urology & nephrology ,Biomarkers, Pharmacological ,03 medical and health sciences ,0302 clinical medicine ,Copeptin ,Predictive Value of Tests ,Recurrence ,Enuresis ,Internal medicine ,Humans ,Medicine ,Desmopressin Acetate ,Deamino Arginine Vasopressin ,Prospective Studies ,Child ,Desmopressin ,Retrospective Studies ,Aquaporin 2 ,business.industry ,Antidiuretic Agents ,Glycopeptides ,Treatment Outcome ,Endocrinology ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists ,Nocturnal Enuresis ,Antidiuretic ,medicine.drug - Abstract
Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone (arginine vasopressin) that is widely used as first line treatment for monosymptomatic nocturnal enuresis. However, no biomarkers to predict desmopressin effectiveness have yet been established. Because arginine vasopressin is unstable, we prospectively measured the major urine concentration factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in patients with monosymptomatic nocturnal enuresis, and evaluated whether they are useful for predicting desmopressin treatment outcome.The study included 32 children 6 to 11 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms and underlying diseases causing nocturnal enuresis. Subjects were treated with 120 μg or 240 μg desmopressin oral disintegrating tablet and were divided into responders (at 120 or 240 μg) and nonresponders (at 240 μg). Day/night ratios of plasma copeptin and urinary aquaporin 2 were measured during desmopressin treatment.There was no significant difference in baseline day/night ratio of urinary aquaporin 2 between desmopressin responders and nonresponders. After 8 weeks of treatment there was a significant correlation between day/night ratio of aquaporin 2 and percentage of wet nights. In responders (but not nonresponders) there was a significant difference in the change in aquaporin 2 day/night ratio from before treatment to complete remission (p = 0.0004). For plasma copeptin the baseline day/night ratio for responders at 120 μg was significantly lower than in the 240 μg nonresponder group (p = 0.02).Urinary aquaporin 2 appears to be a biomarker of desmopressin treatment effectiveness during therapy, while plasma copeptin levels before treatment are predictive of desmopressin response.
- Published
- 2017
41. Association between leg bowing and serum alkaline phosphatase level regardless of the presence of a radiographic growth plate abnormality in pediatric patients with genu varum
- Author
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Sung-Gon Kim, Mayuko Kinoshita, Haruka Kaneko, Masahiko Nozawa, Muneaki Ishijima, Lizu Liu, Yuko Sakamoto, Kazuo Kaneko, Mitsuyoshi Suzuki, Toshiaki Shimizu, Koichi Kamata, and Akifumi Tokita
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Genu varum ,030209 endocrinology & metabolism ,Gastroenterology ,Body Mass Index ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Genu Varum ,030225 pediatrics ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Blood test ,Orthopedics and Sports Medicine ,Growth Plate ,Leg ,medicine.diagnostic_test ,business.industry ,General Medicine ,Odds ratio ,Alkaline Phosphatase ,Confidence interval ,Biomechanical Phenomena ,Child, Preschool ,Regression Analysis ,Alkaline phosphatase ,Female ,Diaphyses ,medicine.symptom ,business ,Body mass index - Abstract
When children around 2 years of age show leg bowing and diseases are ruled out based on radiographic findings without conducting blood tests, they are classified as "physiologic" genu varum. Since whether or not physiologic genu varum is associated with bone metabolism is unclear, this study was conducted to clarify the association between genu varum and bone metabolism in children. Thirty-five pediatric patients with genu varm who visited our out-patient clinic were enrolled. While two of the 35 children had nutritional rickets, showing abnormalities on both blood test (ALP, ≥1000 IU/L; iPTH, >65 pg/mL and 25(OH)D, ≤20 ng/mL) and radiographs (such as cupping, fraying or splaying), five of 35 children showed abnormalities on blood tests but not radiographs. While metaphyseal-diaphyseal angle (MDA) correlated with serum 25-hydroxy vitamin D (r = -0.35, p = 0.04) and magnesium (r = -0.36, p = 0.04), MDA and femorotibial angle (FTA) correlated with alkaline phosphatase (r = 0.43, p = 0.01 and r = 0.51, p = 0.006, respectively). A ridge regression analysis adjusted for age and body mass index indicated that ALP was associated with MDA and FTA. A logistic regression analysis adjusted for age and BMI indicated that higher ALP influenced an MDA >11°, which indicates the risk for the progression of genu varum (odds ratio 1.002, 95% confidence interval 1.0003-1.003, p = 0.021). The higher ALP (+100 IU), the higher risk of an MDA >11° (odds ratio 1.22). In conclusion, genu varum is associated with the alkaline phosphatase level regardless of the presence of radiographic abnormalities in the growth plate in children.
- Published
- 2017
42. Assessment of early diastolic intraventricular pressure gradient in the left ventricle among patients with repaired tetralogy of Fallot
- Author
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Shiori Kawasaki, Mariko Yamada, Maki Kobayashi, Noboru Tanaka, Kana Yazaki, Sachie Shigemitsu, Ken Takahashi, Kotoko Matsui, Masaki Nii, Keiichi Itatani, Toshiaki Shimizu, Katsumi Akimoto, Masahiko Kishiro, and Keisuke Nakanishi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Heart Ventricles ,Diastole ,030204 cardiovascular system & hematology ,Doppler echocardiography ,Ventricular Function, Left ,030218 nuclear medicine & medical imaging ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Ventricular Pressure ,medicine ,Humans ,Circumferential strain ,Postoperative Period ,Prospective Studies ,Cardiac Surgical Procedures ,Child ,Tetralogy of Fallot ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Echocardiography, Doppler ,Cardiac surgery ,medicine.anatomical_structure ,Ventricle ,Child, Preschool ,Intraventricular pressure ,Cardiology ,Early diastolic ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Assessment of left ventricular (LV) dysfunction is vital in patients with repaired tetralogy of Fallot (rTOF). The early diastolic intraventricular pressure gradient (IVPG) in the LV plays an important role in diastolic function. IVPG is calculated as the intraventricular pressure difference divided by the LV length, which allows to account for differences in LV size and therefore calculate IVPG in children. We aimed to investigate the mechanisms of LV diastolic dysfunction by measuring mid-to-apical IVPG as an indicator of the active suction force sucking blood from the left atrium into the LV. We included 38 rTOF patients and 101 healthy controls. The study population was stratified based on age group into children (4–9 years), adolescents (10–15 years), and adults (16–40 years). IVPGs were calculated based on mitral inflow measurements obtained using color M-mode Doppler echocardiography. Although total IVPGs did not differ between rTOF patients and controls, mid-to-apical IVPGs in adolescents and adults were smaller among rTOF patients than among controls (0.15 ± 0.05 vs. 0.21 ± 0.06 mmHg/cm, p
- Published
- 2017
43. Prolonged tacrolimus for pediatric gastrointestinal disorder: Double‐edged sword?
- Author
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Shuichi Ito, Kentaro Matsuoka, Julian Tang, Toshiaki Shimizu, Kenji Hosoi, Atsuko Nakazawa, Koichi Kamei, Katsuhiro Arai, and Hirotaka Shimizu
- Subjects
Male ,medicine.medical_specialty ,Biopsy ,030232 urology & nephrology ,Renal function ,chemical and pharmacologic phenomena ,Autoimmune enteropathy ,Kidney ,Inflammatory bowel disease ,Gastroenterology ,Tacrolimus ,Autoimmune Diseases ,Maintenance Chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Maintenance therapy ,Internal medicine ,Humans ,Medicine ,Renal Insufficiency ,Child ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Infant ,medicine.disease ,Gastroenteritis ,stomatognathic diseases ,Treatment Outcome ,medicine.anatomical_structure ,Gastrointestinal disorder ,Pediatrics, Perinatology and Child Health ,Trough level ,Female ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents - Abstract
Background Although tacrolimus (TAC) can induce remission in children with refractory inflammatory bowel disease (IBD) or autoimmune gastroenteropathy (AGE), its use in maintenance therapy remains controversial. The aim of this study was to investigate the potential nephrotoxic nature of prolonged TAC use. Methods This retrospective study reviewed children with gastrointestinal disorder who underwent kidney biopsy for the evaluation of renal damage during TAC therapy for >1 year. The clinical and histological features of renal damage were evaluated in this single-institution cohort. Results Eighteen of 121 children with IBD and two children with AGE followed at a national children hospital in Tokyo, Japan, received TAC between August 2006 and April 2013. Among them, five (Crohn's disease, n = 3; autoimmune gastropathy, n = 1; autoimmune enteropathy, n = 1) received TAC for >1 year, and underwent kidney biopsy. All five had achieved remission on TAC, but had histological evidence of chronic nephrotoxicity. Renal damage in one patient with relatively low TAC trough level remained mild. Estimated glomerular filtration rate (eGFR) at the time of kidney biopsy was lower than at the initiation of TAC in all four available patients. Among them, eGFR improved in one patient after the decrease or discontinuation of TAC. Conclusions TAC appeared to be effective in children with refractory gastrointestinal disorder, but long-term use seems to cause irreversible renal damage. Rigorous monitoring of eGFR and kidney biopsy in selected cases should be considered for the proper adjustment of TAC.
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- 2017
44. A group of very preterm children characterized by atypical gaze patterns
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Shigeru Kitazawa, Toshiaki Shimizu, Tamami Nakano, Mariko Sekigawa-Hosozawa, and Kyoko Tanaka
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Eye Movements ,genetic structures ,Autism Spectrum Disorder ,Birth weight ,Audiology ,Developmental psychology ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,030225 pediatrics ,medicine ,Humans ,Attention ,Multidimensional scaling ,Child ,Gestational age ,General Medicine ,Chronological age ,medicine.disease ,Gaze ,Very preterm ,Child Development Disorders, Pervasive ,Autism spectrum disorder ,Infant, Extremely Premature ,Pediatrics, Perinatology and Child Health ,Eye tracking ,Female ,Neurology (clinical) ,Psychology ,Photic Stimulation ,030217 neurology & neurosurgery - Abstract
Objective Very preterm (VP) children are at risk for social difficulties, including autism spectrum disorder (ASD). This study used eye tracking to determine viewing behaviors that may reflect these difficulties. Design The gaze patterns of 47 VP (mean gestational age: 28 weeks, mean birth weight: 948 g, and mean chronological age: 49 months) were assessed while viewing dynamic social scenes and compared with those of 25 typically developing (TD) and 25 children with ASD. The temporo-spatial gaze patterns were summarized on a two-dimensional plane using multidimensional scaling (MDS) and the median of the TD children was used to characterize the gazes of the VP children. Time spent viewing the face was also compared. Results The VP children formed two clusters: one had a mean MDS distance comparable to that of TD group (n = 32; VP-small), and the other had a larger mean distance comparable to that of ASD group (n = 15; VP-large). The VP-large were similar to the ASD group by spending significantly less time viewing the face. Their performance was comparable to the TD during the initial 1 s, but they could not remain focused on the face thereafter. Conclusions The VP children were objectively classified into two groups based on gaze behaviors. One group was comparable to TD children, whereas the other had difficulty maintaining attention and exhibited atypical viewing behaviors similar to those of the ASD group. Our method may be useful in identifying VP children at higher risk for experiencing social difficulties.
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- 2017
45. Mechanisms of Left Ventricular Dysfunction Assessed by Layer-Specific Strain Analysis in Patients With Repaired Tetralogy of Fallot
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Toshiaki Shimizu, Kana Yazaki, In-Sam Park, Keisuke Nakanishi, Mariko Yamada, Ken Takahashi, Hirobumi Takayasu, Shiori Kawasaki, Maki Kobayashi, Akio Inage, Tadahiro Yoshikawa, Katsumi Akimoto, and Masahiko Kishiro
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Strain (injury) ,030204 cardiovascular system & hematology ,Ventricular Dysfunction, Left ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,Internal medicine ,Humans ,Circumferential strain ,Medicine ,In patient ,Prospective Studies ,030212 general & internal medicine ,Risk factor ,Child ,Endocardium ,Tetralogy of Fallot ,business.industry ,Myocardium ,General Medicine ,medicine.disease ,Apex (geometry) ,Echocardiography ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Left ventricular (LV) dysfunction in patients with repaired tetralogy of Fallot (rTOF) is an important risk factor for adverse outcomes. The aim of this study was to assess the details and time course of such LV dysfunction using layer-specific strain analysis by echocardiography.Methods and Results:The 66 patients with rTOF (mean age, 16.3±9.3 years) were divided into 3 groups (T1: 4-10 years, T2: 11-20 years, T3: 21-43 years), and 113 controls of similar age (mean age, 17.2±9.3 years) were divided into 3 corresponding groups (C1, C2, and C3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of 3 myocardial layers (endocardial, midmyocardial, and epicardial) were determined by echocardiography. Basal and papillary endocardial CS values were decreased in T1 compared with C1. With the exception of papillary epicardial CS, basal/papillary CS and LS of all 3 layers decreased in T2 compared with C2. Excepting papillary epicardial CS, all other values were decreased in T3 compared with C3. Conclusions Potential myocardial damage was found in the endocardium at the basal and papillary levels of the LV in young patients with rTOF, extending from the endocardium to the epicardium and from the base to the apex. This is the possible time course of LV dysfunction in patients with rTOF.
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- 2017
46. Attitudes toward driver's licenses for people with epilepsy: 2012 versus 2014
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Ayuko Igarashi, Shinpei Abe, Michihiko Takasu, Mika Nakazawa, Mitsuru Ikeno, Toshiaki Shimizu, and Akihisa Okumura
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Male ,Automobile Driving ,Health Knowledge, Attitudes, Practice ,medicine.medical_specialty ,Punishment ,media_common.quotation_subject ,Young Adult ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Japan ,Surveys and Questionnaires ,medicine ,Humans ,030212 general & internal medicine ,Students ,Psychiatry ,media_common ,business.industry ,Accidents, Traffic ,medicine.disease ,Pediatrics, Perinatology and Child Health ,Female ,business ,Attitude to Health ,Licensure ,030217 neurology & neurosurgery - Abstract
Background We compared knowledge about and attitudes toward epilepsy and the issuing of driver's licenses to people with epilepsy among non-medical students before and after media controversies. Methods The survey was performed in 2012 and 2014 using a structured questionnaire. Participants were non-medical students who attended a lecture on neurological diseases in children. The proportion of positive answers to each question in 2012 was compared with that in 2014. In addition, questions regarding attitudes toward driver's licenses were compared according to knowledge about car accidents linked to people with epilepsy. Results More participants were familiar with epilepsy and had a favorable attitude toward epilepsy in 2014 than in 2012. In contrast, the proportion of participants who knew of car accidents linked to people with epilepsy was reduced in 2014 compared with 2012. The proportion of participants who did not think that severe punishment should be given to people with epilepsy if they caused a car accident decreased in 2014 among those without knowledge of car accidents. Conclusions Familiarity with and attitudes toward epilepsy were improved in 2014, whereas the decrease in proportion of positive answers on punishment among participants unfamiliar with car accidents suggests a latent worsening of public attitudes.
- Published
- 2016
47. Is a pediatrician performed gray scale ultrasonography with power Doppler study safe and effective for triaging acute non-perforated appendicitis for conservative management?
- Author
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Reiko Kyodo, Eri Miyata, Atsuyuki Yamataka, Geoffrey J. Lane, Hiroshi Murakami, Masahiro Takeda, Keisuke Jimbo, Hideki Orikasa, and Toshiaki Shimizu
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Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Conservative management ,030230 surgery ,Conservative Treatment ,Asymptomatic ,03 medical and health sciences ,Power doppler ,0302 clinical medicine ,030225 pediatrics ,Humans ,Medicine ,Emergency appendectomy ,Pediatricians ,Child ,Interval appendectomy ,Retrospective Studies ,Ultrasonography, Doppler, Duplex ,business.industry ,General Medicine ,Blood flow ,Appendicitis ,medicine.disease ,Surgery ,Child, Preschool ,Acute Disease ,Pediatrics, Perinatology and Child Health ,Female ,Triage ,medicine.symptom ,Ultrasonography ,business - Abstract
Purpose The purpose of this study was to examine whether acute non-perforated appendicitis (ANPA) can be safely triaged by a pediatrician for conservative management (CM) using gray-scale ultrasonography with power Doppler (GSPD). Method Seventy five cases of ANPA assessed by a pediatrician with GSPD (2013–2015) were reviewed. GSPD grading for ANPA was: I: slightly irregular wall/normal blood flow; II: irregular wall/increased blood flow; III: irregular wall/decreased blood flow; and IV: absence of wall/blood flow. Grades I/II were managed conservatively with intravenous antibiotics then encouraged to book for interval appendectomy (IA). Grades III/IV were reviewed for emergency appendectomy (EA) by a pediatric surgeon. Results GSPD grading was I ( n =26), II ( n =36), III ( n =9), and IV ( n =4). EA was required for 5 cases, one grade III, and four grade IV cases. One grade IV case was treated conservatively after surgical review but EA was unavoidable. Of the remaining 70 cases discharged well after a mean of 5.7days hospitalization, 25/70 had IA with chronic inflammation on histology, 6/70 had recurrence of ANPA treated successfully by EA, and 39/70 remain asymptomatic at least 10months after declining IA. Overall, GSPD triaging with CM was cheaper than surgery. Conclusions GSPD performed by pediatricians appears to be safe/effective for triaging ANPA. Level of evidence Level III.
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- 2016
48. Worsening of attitudes toward epilepsy following less influential media coverage of epilepsy-related car accidents: An infodemiological approach
- Author
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Hirokazu Kurahashi, Michihiko Takasu, Ayuko Igarashi, Mitsuru Ikeno, Akihisa Okumura, Toshiaki Shimizu, Mika Nakazawa, and Shinpei Abe
- Subjects
Male ,Health Knowledge, Attitudes, Practice ,medicine.medical_specialty ,Injury control ,Information Seeking Behavior ,Poison control ,Media coverage ,Suicide prevention ,Occupational safety and health ,Thinking ,Young Adult ,03 medical and health sciences ,Behavioral Neuroscience ,Epilepsy ,0302 clinical medicine ,Surveys and Questionnaires ,Injury prevention ,Humans ,Medicine ,Mass Media ,030212 general & internal medicine ,Students ,Psychiatry ,Internet ,business.industry ,Accidents, Traffic ,Human factors and ergonomics ,Recognition, Psychology ,medicine.disease ,Neurology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
To evaluate changes in the attitudes of nonmedical university students toward epilepsy in 2015, the present study compared the results of questionnaire surveys from four different time periods: before media coverage of epilepsy-related car accidents (2008–2010), during a period of abundant media coverage (2011–2012), after media coverage (2013–2014), and after novel media coverage (2015). The nonmedical students that completed the questionnaire were divided into four groups: 2008–2010, 2011–2012, 2013–2014, and 2015. The rates of students that had read or heard about epilepsy decreased significantly in 2015 compared with those in 2013–2014. Attitudes toward epilepsy had also worsened in 2015. The rates of students that would not oppose their children playing with or attending school alongside children with epilepsy and those who thought that people with epilepsy should be hired in the same way as other people had decreased significantly in 2015 compared with those in 2011–2012 and 2013–2014. Analyses of information-seeking behavior on the Internet showed that the increase in Google search volume and Wikipedia page views was much less in 2015 than in 2011 and 2012. These findings suggest that familiarity with epilepsy had worsened even after media coverage of novel epilepsy-related car accidents. This suggests that media coverage in 2015 was less influential than that in 2011 and 2012.
- Published
- 2016
49. Is SPINK1 gene mutation associated with development of pancreatic cancer? New insight from a large retrospective study
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Toshiaki Shimizu and Mitsuyoshi Suzuki
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Oncology ,Male ,medicine.medical_specialty ,Trypsin inhibitor ,General Biochemistry, Genetics and Molecular Biology ,Pancreatic cancer ,Internal medicine ,Pancreatitis, Chronic ,medicine ,SPINK1 Gene ,Humans ,Genetic Predisposition to Disease ,Retrospective Studies ,business.industry ,Age Factors ,Retrospective cohort study ,General Medicine ,medicine.disease ,Pancreatic Neoplasms ,Trypsin Inhibitor, Kazal Pancreatic ,Mutation (genetic algorithm) ,Mutation ,Commentary ,Pancreatitis ,Female ,business - Published
- 2019
50. Notch signaling contributes to the establishment of sustained unresponsiveness to food allergens by oral immunotherapy
- Author
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Hiromichi Yamada, Ko Okumura, Tomoaki Ando, Hideoki Ogawa, Ayako Kaitani, Mutsuko Hara, Nobuhiro Nakano, Koichiro Uchida, Yoshikazu Ohtsuka, Kumi Izawa, Toshiaki Shimizu, Toshiyuki Yoneyama, and Jiro Kitaura
- Subjects
0301 basic medicine ,Ovalbumin ,medicine.medical_treatment ,Immunology ,Notch signaling pathway ,Administration, Oral ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Th2 Cells ,Food allergy ,medicine ,Immune Tolerance ,Immunology and Allergy ,Animals ,Humans ,Cells, Cultured ,Desensitization (medicine) ,Mice, Inbred BALB C ,biology ,Receptors, Notch ,Chemistry ,Myeloid-Derived Suppressor Cells ,Allergens ,medicine.disease ,Interleukin-10 ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Desensitization, Immunologic ,030220 oncology & carcinogenesis ,biology.protein ,Myeloid-derived Suppressor Cell ,Cancer research ,Female ,Bone marrow ,Antibody ,Food Hypersensitivity ,Signal Transduction - Abstract
Background Oral immunotherapy (OIT) aims to establish desensitization and sustained unresponsiveness (SU) in patients with food allergy by ingestion of gradually increasing doses of specific food allergens. However, little is known about the mechanisms by which OIT induces SU to specific allergens. Objectives We investigated the role of Notch signaling, which controls cell fate decisions in many types of immune cells in the induction of SU by OIT treatment. Methods Two types of mouse models, ovalbumin-induced food allergy and OIT, were generated. To elucidate the role of Notch signaling in OIT-induced SU, mice were intraperitoneally injected with the Notch signaling inhibitor N-[(3,5-difluorophenyl)acetyl]- l -alanyl-2-phenylglycine-1,1-dimethylethyl ester during the OIT treatment period. Results Ovalbumin-sensitized mice were desensitized and also had SU induced by OIT treatment, whereas repeated challenges with ovalbumin caused the development of severe allergic reactions in ovalbumin-sensitized mice. Administration of N-[(3,5-difluorophenyl)acetyl]- l -alanyl-2-phenylglycine-1,1-dimethylethyl ester to mice during the OIT treatment period inhibited the establishment of SU to ovalbumin but did not affect the induction of desensitization. OIT induced a systemic expansion of IL-10–producing CD4+ T cells, including TH2 cells, and myeloid-derived suppressor cells (MDSCs), particularly the monocytic MDSC subpopulation. Inhibition of Notch signaling prevented the OIT-induced expansion of those cells. In vitro cultures of bone marrow cells showed that Notch signaling directly promoted the generation of monocytic MDSCs. In addition, the contribution of MDSCs to OIT-induced SU was confirmed by MDSC depletion with the anti-Gr1 antibody. Conclusion Notch signaling contributes to the establishment of SU induced by OIT through systemic expansion of immunosuppressive cells, such as IL-10–producing CD4+ T cells and MDSCs.
- Published
- 2019
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