Incidence rate of vitamin D deficiency and FGF23 levels in 12- to 13-year-old adolescents in Japan.

INTRODUCTION: The incidence rate of vitamin D deficiency is increasing throughout the world. We measured the incidence rate of vitamin D deficiency and fibroblast growth factor 23 (FGF23) levels in 12- to 13-year-old adolescents in Japan. MATERIALS AND METHODS: A total of 492 adolescents (247 boys and 245 girls) from Japanese community enrolled in this study. 25 hydroxyvitamin D (25(OH)D) was measured with radioimmunoassay. In the subjects with low 25(OH)D levels (≦ 20 ng/ml), intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), albumin (Alb), alkaline phosphatase (ALP) and FGF23 were measured. RESULTS: 25(OH)D levels were significantly lower in girls (20.9 ± 3.1 ng/ml) than in boys (22.2 ± 3.3 ng/ml) (p < 0.0001). Fifty-five boys (22.3%) and 83 (33.9%) girls showed vitamin D deficiency (< 20 ng/ml). One-hundred eighty-six (75.3%) boys and 162 (66.1%) girls showed vitamin D insufficiency (≧ 20 ng/ml, < 30 ng/ml). In the subjects whose 25(OH)D levels were ≦ 20 ng/ml, the levels of iPTH, Ca, P, Alb, ALP and FGF23 were 22.3 ± 9.0 pg/ml, 9.5 ± 0.4 mg/dl, 4.7 ± 0.6 mg/dl, 4.6 ± 0.3 g/dl, 920.8 ± 339.3 U/l and 42.6 ± 26.0 pg/ml, respectively. There was a significant negative association between serum 25(OH)D levels and iPTH [r = - 0.290 (p < 0.0001)]. There was no significant association between serum 25(OH)D levels and FGF23. CONCLUSION: We show that 28% of Japanese 12- to 13-year-old early adolescents suffer from vitamin D deficiency. Findings from this study indicate that vitamin D deficiency requires close oversight in public health during adolescence to ensure proper bone health.

Necrotizing Ulcer After BCG Vaccination in a Girl With Leukocyte-adhesion Deficiency Type 1.

Leukocyte-adhesion deficiency-1 is a recessively inherited disorder associated with recurrent bacterial infections, severe periodontitis, peripheral leukocytosis, and impaired wound healing. We diagnosed moderate-type leukocyte-adhesion deficiency-1 in a 7-year-old girl who developed a necrotizing ulcer after Bacillus Calmette-Guerin vaccination. The patient showed moderate expression of CD18 in neutrophils with a homozygous splice mutation with c.41_c.58+2dup20 of ITGB2 and experienced recurrent severe infections complicated with systemic lupus erythematosus. She received hematopoietic stem cell transplantation from a matched elder brother with heterozygous mutation of ITGB2, and has since remained free of infection and systemic lupus erythematosus symptoms without immunosuppression therapy.

Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study in Japan using a nationwide registry.

Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been evaluated in clinical trials and has not been approved in any developed country. We aimed to test the efficacy and safety of octreotide for diazoxide-unresponsive CHI through a combination of a single-arm, open-label clinical trial (SCORCH study) and an observational study to collect data on the clinical course of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5 patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose infusion, and treated by continuous subcutaneous octreotide infusion at a dose of 5-25 µg/kg/day. Continuous blood glucose monitoring was performed between -24 and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was achieved and therapy was continued. The glucose infusion was gradually decreased and stopped after 5, 11, and 174 days, respectively. In one case, remission of CHI was reached after 606 days and octreotide was discontinued. The SCORCH registry included 19 diazoxide-unresponsive patients treated by subcutaneous octreotide, by continuous infusion or multiple daily injections. Of the 17 patients treated with hypertonic glucose infusion, the infusion rate was reduced after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%). During the combined observation period of 695.4 patient-months in both studies, no severe adverse events related to octreotide were observed. In conclusion, subcutaneous octreotide injection was effective and well tolerated in the majority of patients with diazoxide-unresponsive CHI.

Safety of lipid emulsion in very low-birthweight infants according to cytokine level.

BACKGROUND: The aim of this study was to verify whether lipid emulsion treatment aggravates infection and inflammation in very low-birthweight (VLBW) infants. STUDY DESIGN: Very low-birthweight (<1500 g) infants born at <32 weeks gestational age between October 2013 and October 2014 at Dokkyo Medical University Hospital (Mibu, Tochigi, Japan) were treated with or without i.v. nutrition with a lipid emulsion. Infants were excluded who had congenital abnormalities, could not receive i.v. nutrition because of poor general condition, or on physician decision. Lipid emulsion with purified soybean oil was initiated at 0.5 g/kg/day on postnatal day 1. The dose was increased to 1 g/kg/day, and then to 1.5 g/kg/day (maximum dose). Blood tests were performed before (day 1) and after (day 8) initiation of lipid emulsion treatment. Interleukin (IL)-6, IL-8, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), total bilirubin (T-Bil), direct bilirubin (D-Bil) and insulin were measured. Changes in respiratory condition, amount of oxygen used, and phototherapy duration were investigated. RESULTS: A total of 17 treated and 15 untreated VLBW infants were enrolled. IL-6, IL-8, MCP-1, TNF-α, CRP, T-Bil, D-Bil and insulin on days 1 and 8; respirator or surfactant use; amount of oxygen used; and phototherapy duration were not significantly different between the two groups. CONCLUSIONS: Lipid emulsion treatment did not increase inflammatory cytokine levels or aggravate respiratory disorders. Lipid emulsions, if proven safe, could be used to treat VLBW infants soon after birth, which may prevent extrauterine growth restriction and improve intellectual development prognosis.

Fetal Bone Formation Is Decreased from Middle Pregnancy to Birth.

Fetal bone development is a complex process that is regulated and maintained by minerals, hormones, and growth factors delivered from the mother via the placenta. Various biochemical markers of fetal bone development have been identified. However, many aspects of this process remain unclear. The aim of the study was to measure the activities of serum tartrate-resistant acid phosphatase type 5b (TRACP 5b) as a bone resorption marker and bone alkaline phosphatase (BAP) as a bone formation marker in preterm and term neonates, and to investigate fetal bone development in middle and late pregnancy. The study included 111 neonates (87 preterm and 24 term) born at Dokkyo Medical University Hospital. Neonates with illnesses and maternal diseases were excluded. Serum samples were collected within 3 hours after birth and stored at -80°C. Univariate and multivariate linear regression analyses were performed. The 111 neonates (median birth weight, 1,510 g) were born at a median of 31.3 weeks of gestation, and had TRACP 5b and BAP activities of 10.9 ± 4.0 U/L and 127.5 ± 49.2 U/L, respectively. TRACP 5b activity showed a tendency to be higher in term neonates, while BAP activity tended to be lower in term neonates. Importantly, TRACP 5b activity was positively correlated with gestational age and birth weight, and BAP activity was negatively correlated with gestational age, rate of born small-for-gestational-age neonates, and birth weight. These results suggest that bone formation during fetal growth is gradually decreased from middle pregnancy to birth, whereas bone resorption is gradually increased.

Prevalence of childhood asthma in Ulaanbaatar, Mongolia in 2009.

BACKGROUND: Bronchial asthma is a common but important chronic disease in children in all over the world. To take measures against prevalence of childhood asthma, many researchers have surveyed the actual statuses of childhood asthma in developed countries, but in most Asia-Pacific developing countries including Mongolia such surveys have never been sufficiently conducted until now. We have thought that this survey, though performed in 2009, will give important and meaningful information even now in taking measures to prevent prevailing bronchial asthma in children in Mongolia or the countries under similar statuses. METHODS: The asthma prevalence and patient background information in Mongolian children aged 6-7 living in Ulaanbaatar were examined using a written questionnaire modified for their parents from that prepared by the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: The estimated prevalence of asthma in Mongolian children was 20.9%. The following 3 risk factors were found to be related to asthma: (1) having allergic rhinitis symptoms, (2) mothers' smoking, and (3) history of severe respiratory infection before 1-year-old. CONCLUSIONS: The asthma prevalence in Mongolian children was higher than that in the world and Asia-Pacific countries reported by ISAAC. The higher prevalence was probably attributable to households' (especially mothers) smoking in draft-free houses designed for the cold area and severe air-pollution due to rapid industrialization and urbanization in Mongolia. Smoking prohibition in the mother (including family members) and a reduction of exposure to air pollutants are urgently needed to prevent developing childhood asthma.

Association between timing of adiposity rebound and body weight gain during infancy.

OBJECTIVE: To investigate whether increments of weight gain in early infancy are related to the timing of adiposity rebound (AR). STUDY DESIGN: A total of 271 children (147 boys and 124 girls) in 1 community were enrolled in the study. Serial measurements of body mass index were carried out at the ages of 4, 8, and 12 months and 1.5, 2, 3, 4, 5, 6, 7, 8, 9, and 10 years, based on which the age of AR was determined. We also calculated body weight increments in 3 separate periods: birth to 4 months, 4-8 months, and 8-12 months. RESULTS: There was no significant relationship between weight gain in any period of infancy and the age of AR. Weight gain between birth and 4 months was positively correlated only with body mass index at 7 years of age. CONCLUSIONS: We could not find an association between body weight gain during infancy and the timing of AR. This suggests that infantile weight gain is not related to childhood obesity through AR.

Caregiver treatment satisfaction is improved together with children's asthma control: Prospective study for budesonide monotherapy in school-aged children with uncontrolled asthma symptoms.

BACKGROUND: If asthmatic children cannot obtain sufficient control of their disease, not only do they suffer from asthma symptoms, but the daily life activities of their caregivers are also disrupted. We investigated the effectiveness of an inhaled corticosteroid (ICS) for symptom control in previously ICS-untreated school-aged asthmatic children as well as caregiver treatment satisfaction (CTS). METHODS: A multicenter, open-label, single-arm study on 12-week ICS (budesonide Turbuhaler®) monotherapy was undertaken in subjects aged 5-15 years with bronchial asthma not treated with ICS during the previous 3 months. At 0, 4, 8, and 12 weeks after start of ICS administration, Japanese Pediatric Asthma Control Program (JPAC) scores, and CTS scores were summated and lung function measured. At weeks 0 and 12, questionnaires on caregiver anxiety were also assessed. RESULTS: Seventy-five patients were enrolled, and 69 assessed. Ninety percent of subjects had been treated with asthma controller medication except ICS before study enrollment. JPAC score and CTS score were improved significantly at weeks 4, 8, and 12 (p < 0.001). With regard to CTS, more than half of caregivers showed a perfect score at weeks 8 and 12. There was a significant correlation between JPAC score and CTS score. Lung function and caregiver anxiety were also improved, and good compliance with treatment was observed during the intervention. CONCLUSIONS: If treating ICS-untreated school-aged asthmatic children with uncontrolled symptoms, ICS monotherapy can improve CTS along with improving asthma control.

Necessary stem cell transplantation using myeloablative therapy for myelodysplastic syndrome with progression of genotypic abnormalities and TP53 dysfunction in a young adult.

A 14-yr-old male was admitted to our hospital with MDS and the chromosomal abnormality 45,XY,der(5;17)(p10;q10). He rapidly developed karyotype abnormalities, accompanied by the loss of tumor suppressor gene TP53 function. He suffered an early relapse after reduced-intensity-conditioning SCT and ultimately required myeloablative therapy before a second SCT. We consider that the analysis of TP53 mutations is essential when planning the treatment of patients with MDS.