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Okabe Y.,University of Toyama | Adachi Y.,University of Toyama | Itazawa T.,University of Toyama | Yoshida K.,Tokyo Metropolitan Childrens Hospital | And 4 more authors.
Pediatric Allergy and Immunology | Year: 2012

Obesity may increase the risk of subsequent asthma. We have previously reported that there is a clear association between obesity and asthma in Japanese school-aged children. To evaluate whether a similar association exists in younger children, a nationwide cross-sectional questionnaire-based survey was performed focusing on children aged 4-5yr. A child who had experienced wheezing during the past 12months and had ever been diagnosed with asthma by a physician was defined as having current asthma. Overweight and underweight were defined as BMI ≥90th percentile and ≤10th percentile, respectively, according to the reference values for Japanese children from 1978 to 1981. After excluding 2547 children because of incomplete data, 34,699 children were analyzed. Current asthma was significantly more prevalent in overweight children compared with underweight and normal weight children (13.2% for overweight vs. 10.5% for underweight and 11.1% for normal weight; both p<0.001). Even after adjusting for other variables, such as gender, other coexisting allergic diseases, and parental history of asthma, there was an association between overweight and current asthma (adjusted odds ratio: 1.23, 95% CI: 1.10-1.38, p<0.001). Even in preschool children, obesity is already associated with asthma, and there was no gender effect on this association. Physicians should consider the impact of obesity when managing asthma in younger children. © 2011 John Wiley & Sons A/S.


Okabe Y.,University of Toyama | Itazawa T.,University of Toyama | Adachi Y.,University of Toyama | Yoshida K.,National Center for Children Health and Development | And 4 more authors.
Pediatrics International | Year: 2011

Background: Most studies regarding the association of obesity with asthma have been performed in the Western countries. This study is a nationwide survey conducted in Japan. Methods: A cross-sectional and questionnaire-based survey was performed among children aged 6-7, 13-14, and 16-17 years, using the ISAAC questionnaire. Overweight was defined as BMI ≥ 90th according to the reference values for Japanese children obtained during 1978-1981. Results: Of a total of 179 218 children, 149 464 replied to the questionnaire (response rate 83.4%). After omitting incomplete data, 139 117 were analyzed. In all the age groups, being overweight was associated with current asthma after adjustment for confounding factors (adjusted OR: 1.24 in children 6-7 years of age, 1.31 in those 13-14 years, and 1.32 in those 16-17 years). These tendencies were observed in both genders. Overweight was a risk factor for nocturnal cough, independent of current asthma in the older age groups (adjusted OR: 1.21 in children 13-14 years, and 1.17 in those 16-17 years). Conclusions: There is a clear association between obesity and current asthma in Japanese school-aged children. Mechanisms through which obesity related with nocturnal cough might be different from those of obesity-associated asthma. © 2011 The Authors.


PubMed | Kawakita General Hospital, National Center for Child Health and Development, Tokyo Metropolitan Childrens Hospital and The Interdisciplinary Center
Type: | Journal: Systematic reviews | Year: 2016

Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormality in children. Based on reports of elevated plasma level of cytokines such as tumor necrosis factor- in KD patients, clinical trials of monoclonal antibodies that block cytokine cascades have been conducted. However, the studies have revealed contradictory results. The objective of this study is to examine the effectiveness of treatment with monoclonal antibodies for KD patients.Relevant randomized controlled trials (RCTs), cluster RCTs, quasi-RCTs, cross-over trials, and any observational studies (e.g., cohort studies, case-control studies, case series, and case reports) will be included to summarize available evidence both qualitatively and quantitatively. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI will be searched. We will assess coronary artery and treatment outcomes of the interventions. Two authors will independently screen studies for inclusion and consulting with a third author where necessary to resolve discrepancies. The risk of bias of included studies will be assessed using the Cochrane Collaboration risk of bias tool and quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis of the included studies will be conducted using fixed effects or random effects models depending on the degree of between-study heterogeneity. Results will be presented using risk ratios with 95 % confidence interval (CI) for dichotomous outcomes and standardized mean differences with 95 % CI for continuous outcomes.This systematic review and meta-analysis protocol does not require ethical approval. We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.PROSPERO CRD42016033079 .


Tanaka Y.,Dokkyo Medical University | Yoshikawa N.,Wakayama Medical University | Hattori S.,Kumamoto Health Science University | Sasaki S.,Hokkaido University | And 3 more authors.
Pediatric Nephrology | Year: 2010

The initial treatment of childhood-onset systemic lupus erythematosus (SLE) is not standardized. Although corticosteroids are the first-line therapy for SLE, long-term, high-dose steroid therapy is associated with various side effects in children. The Japanese Study Group for Renal Disease in Children (JSRDC) has carried out a multi-center, randomized, controlled trial to evaluate the efficacy and safety of corticosteroid and mizoribine (MZB) therapy as an initial treatment for newly diagnosed juvenile SLE. Twenty-eight patients were treated with a combination steroid and MZB (4-5 mg/kg/day) (group S+M) drug therapeutic regimen, while 29 patients were treated with steroid only (group S); both groups were followed up for 1 year. The time to the first flare from treatment initiation was not significantly different between the two groups (Kaplan-Meier method, p = 0.09). During the period when the steroid was given daily (day 0-183), the time to the first flare from treatment initiation was significantly longer in the patients of group S+M than in those of group S (log-rank test, p = 0.02). At the end of the study period, there were no differences in the severity of proteinuria and renal function impairment between the two groups. No patients dropped out of the trial due to adverse events. In conclusion, our combined steroid and MZB drug therapeutic regimen was not shown to be significantly better than the steroid-only therapy as initial treatment for juvenile SLE. Whether MZB administered in a higher dose would be therapeutically advantageous can only be answered by further studies. © 2009 IPNA.


PubMed | Tokyo Metropolitan Childrens Hospital and Toho University
Type: Journal Article | Journal: Transplantation direct | Year: 2016

Children with a compromised inferior vena cava (IVC) were previously considered unsuitable for kidney transplantation because of the technical difficulties and the increased risk of graft thrombosis secondary to inadequate renal venous outflow.We conducted a retrospective study of 11 transplants in 9 patients with end-stage renal disease and thrombosed IVCs who received adult kidney allografts between 2000 and 2015. The mean age at transplantation was 7.5 3.5 years. A pretransplant diagnosis of the IVC thrombosis was made in 7 patients by magnetic resonance imaging and computerized tomography, whereas there were 2 instances of intraoperative discovery of the IVC thrombosis.In the early cases, a kidney was placed intraperitoneally at the right iliac fossa with a venous anastomosis to the patent segment of the suprarenal IVC. After 2008, however, 6 adult-sized kidneys were subsequently placed in the left orthotopic position. Venous drainage was attained to the infrahepatic IVC (n = 3), left native renal vein (n = 2), and ascending lumbar vein (n = 1). Moreover, a venous bypass was created between the graft and the splenic vein in 2 children who showed high return pressure after the vessel was declamped. The mean glomerular filtration rate of the functioning 8 grafts 1 year posttransplant was 73.4 20.4 mL/min per 1.73 m(2). Of note, 6 of the grafts have been functioning well, with a mean follow-up of 66 months. Both 1- and 5-year graft survival were 81.8%.Transplantation into the left orthotopic position and the revascularization methods are an effective set of surgical techniques that could potentially be adopted as safe and reliable transplant approaches in children with IVC thrombosis.


Shinohara M.,Tokyo Medical University | Saitoh M.,Tokyo Medical University | Takanashi J.-I.,Kameda Medical Center | Yamanouchi H.,Saitama University | And 6 more authors.
Brain and Development | Year: 2011

The high incidence of acute encephalopathy in East Asia suggests the role of genetic factors in its pathogenesis. It has recently been reported that variations of the CPT II (carnitine palmitoyl transferase II) gene may be associated with fatal or severe cases of influenza-associated encephalopathy. In the present study, we examined the genotype of CPT II in cases of acute encephalopathy associated with various preceding infections. Twenty-nine Japanese patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) or acute necrotizing encephalopathy (ANE) were studied. The frequency of F352C of CPT II exon 4 was significantly higher in patients than in controls. All patients who had allele C in F352C had allele I in V368I and allele M in M647V (CIM haplotype), which reportedly decreases CPT II activity to one third of that with FIM or FVM haplotype. The frequency of CIM haplotype was significantly different between patients and controls, but not between AESD and ANE. Our results revealed that having at least one CIM allele is a risk factor for the onset of acute encephalopathy, regardless of its antecedent infections. © 2010 The Japanese Society of Child Neurology.


Honda M.,Tokyo Metropolitan Childrens Hospital | Warady B.A.,Childrens Mercy Hospital
Pediatric Nephrology | Year: 2010

Encapsulating peritoneal sclerosis (EPS) is the most serious complication of long-term peritoneal dialysis (PD), with a mortality rate that exceeds 30%. There have been many reports of the incidence of EPS being strongly correlated to the duration of PD. Patients on PD for longer than 5 years, and especially those receiving this treatment for more than 8 years, should undergo careful and repeated surveillance for risk factors associated with the development of EPS. The development of ultrafiltration failure, a high dialysate/plasma creatinine ratio, as determined by the peritoneal equilibration test, peritoneal calcification, a persistently elevated C-reactive protein level, and severe peritonitis in patients on PD for longer than 8 years are signals that should prompt the clinician to consider terminating PD as a possible means of preventing the development of EPS. The impact of the newer, biocompatible PD solutions on the incidence of EPS has not yet been determined. © 2008 IPNA.


Yoshihashi H.,Tokyo Metropolitan Childrens Hospital | Yoshihashi H.,Gunma Childrens Medical Center | Yoshihashi H.,Keio University | Ohki H.,Tokyo Metropolitan Childrens Hospital | And 4 more authors.
Pediatric Dermatology | Year: 2011

We report a 46,XY boy with a mild focal dermal hypoplasia phenotype who had both wild-type and mutated copies of the PORCN gene and was, therefore, mosaic for the mutation. He had cutaneous syndactyly, hydronephrosis, and nail dystrophy. Small whitish depigmented spots, which were slightly depressed from the skin surface, were distributed linearly on the trunk and arms. Aside from these findings, streaks of brown-pigmented macules were seen on the dorsal aspect of the legs. Both the linear arrangement of the whitish spots and the streaks of pigmented macules followed the lines of Blaschko. The phenotype of the patient, who did not exhibit cribriform atrophy, telangiectasia or fat herniation, seemed to be much milder than that of typical female patients with focal dermal hypoplasia. Analysis of the genomic DNA extracted from the peripheral lymphocytes revealed a transition 129G>A within exon 1 of PORCN, which leads to a nonsense mutation W43X. The percentage of peripheral lymphocytes carrying a mutation was estimated to be 50% by the subcloning and sequencing of individual clones of the PCR product amplified across the mutation. This patient's case history provides further molecular evidence supporting the concept that "male focal dermal hypoplasia" does exist and that typical features such as telangiectasia and fat herniation are sometimes absent. © 2010 Wiley Periodicals, Inc.


Igaki J.M.,Tokyo Metropolitan Childrens Hospital | Yamada M.,Tokyo Metropolitan Childrens Hospital | Yamazaki Y.,Kyowa Hakko Kirin Co. | Koto S.,Tokyo Metropolitan Childrens Hospital | And 5 more authors.
Endocrine Journal | Year: 2011

X-linked hypophosphatemic rickets (XLH) is caused by inactivating mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) gene. Deletion of Phex leads to increased serum fibroblast growth factor23 (FGF23) levels in mouse. The aim is to assure the clinical usefulness of FGF23 determination in the diagnosis of XLH. Participants were 21 patients with XLH having abnormalities in PHEX from 13 kindred (PtPHEX: 1 to 42 years old; 10 males, 11 females) and 55 healthy controls (1 month to 18 years old; 27 males, 28 females). Temporal changes in FGF23 were determined by a single oral phosphate administration in PtPHEX and an ad lib diet in controls. Reference ranges of intact FGF23 (iFGF23) for children were determined. iFGF23 level which distinguish between controls and PtPHEX were validated. Correlations between iFGF23 and the severity of XLH (gender, age of onset, bone deformity, The ratio of maximum rate of renal tubular reabsorption of phosphate to glomerular filtration rate (TmPO 4/ GFR), inorganic phosphate (IP), Alkaline Phosphatase (ALP), therapeutic dose) were investigated. Increasing tendency after phosphate administration and no general tendency after breakfast in iFGF23 were observed. Reference range (5 th and 95 th percentiles) of iFGF23 for children (12.9 and 51.2 pg/mL) was similar to that for adults. iFGF23 were above the reference range in 19 of 21 PtPHEX (40 to 4710 pg/mL). iFGF23 did not correlate with any index of severity of XLH. Relatively high iFGF23 despite hypophosphatemia is one of the clinical indicators to diagnose XLH. © The Japan Endocrine Society.


Hasegawa Y.,Tokyo Metropolitan Childrens Hospital
Clinical calcium | Year: 2013

Rickets is a condition of inadequate mineralization of osteoid and cartilage at the growing ends of bones in children. In this brief review, we first explained the regulation of serum Ca and P concentrations to understand Rickets. Second, four types of sub-division of Rickets are presented ; 1) Vitamin D dysfunction-related, 2) Phosphate deficiency-related, 3) both 1) and 2) -related, 4) others. Finally, as most common entities, diagnosis and treatment in vitamin D deficiency and inherited hypophosphatemic Rickets/Osteomalacia are described. Over production of Klotho and inactivating mutations of FAM20c are explained as recent etiologies of non-hypercaluciuric inherited hypophosphatemic Rickets/Osteomalacia.

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