小学４年生のこころの発達理解と対応

本講演では、小学４年生の心身の発達理解、発達の個人内差異と個人差、子どもとの日常的な会話・対応、家族の雰囲気・親子関係、子どもの存在をどうとらえるか、対人的関係性とその特質、聴くこととその意義などについて話した。lectur

Long-Term Follow-Up of Autoimmune Pancreatitis: Characteristics of Chronic Disease and Recurrence

Autoimmune pancreatitis is a unique disease, characterized by lymphoplasmacytic inflammation in the acute stages. However, the active clinical features are unlikely to persist for long periods. Through long-term follow-up, we investigated the disease course in 51 patients with autoimmune pancreatitis. We found recurrence in 21 (41%) patients and pancreatic stone formation in 9 (18%) patients. Pancreatic stone formation was significantly more frequent in the recurrence group (7/21, 33%), compared with the nonrecurrence group (2/30, 7%). Moreover, we found high serum immunoglobulin G4 concentrations in 13 of 175 (7.4%) patients with ordinary chronic pancreatitis. This suggested that pancreatic stone formation is closely associated with recurrence and that autoimmune pancreatitis might transform into ordinary chronic pancreatitis after several recurrences. We found that the immune complex level, with a cutoff value of 10 mu g/dL, served as a good predictor of recurrence, with high sensitivity (61.9%), specificity (70.0%), and efficacy (66.7%). We also confirmed that HLA and cytotoxic T-lymphocyte antigen-4 polymorphisms were useful predictors for AIP recurrence.ArticleCLINICAL GASTROENTEROLOGY AND HEPATOLOGYjournal articl

Clinical and genetic aspects of mild hypophosphatasia in Japanese patients

Background: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from a dysfunctional tissue non-specific alkaline phosphatase enzyme (TNSALP). Although genotype-phenotype correlations have been described in HPP patients, only sparse information is currently available on the genetics of mild type HPP. Methods: We investigated 5 Japanese patients from 3 families with mild HPP (patients 1 and 2 are siblings; patient 4 is a daughter of patient 5) who were referred to Fujita Health University due to the premature loss of deciduous teeth. Physical and dental examinations, and blood, urine and bone density tests were conducted. Genetic analysis of the ALPL gene was performed in all patients with their informed consent. Results: After a detailed interview and examination, we found characteristic symptoms of HPP in some of the study cases. Mobile teeth or the loss of permanent teeth were observed in 2 patients, and 3 out of 5 patients had a history of asthma. The serum ALP levels of all patients were 30% below the lower limit of the age equivalent normal range. ALPL gene analysis revealed compound heterozygous mutations, including Ile395Val and Leu520Argfs in family 1, Val95Met and Gly491Arg in family 2, and a dominant missense mutation (Gly456Arg) in family 3. The 3D-modeling of human TNSALP revealed three mutations (Val95Met, Ile395Val and Gly456Arg) at the homodimer interface. Severe collisions between the side chains were predicted for the Gly456Arg variant. Discussion: One of the characteristic findings of this present study was a high prevalence of coexisting asthma and a high level serum IgE level. These characteristics may account for the fragility of tracheal tissues and a predisposition to asthma in patients with mild HPP. The genotypes of the five mild HPP patients in our present study series included 1) compound heterozygous for severe and hypomorphic mutations, and 2) dominant-negative mutations. All of these mutations were at the homodimer interface, but only the dominant-negative mutation was predicted to cause a severe collision effect between the side chains. This may account for varying mechanisms leading to different effects on TNSALP function

Long-term outcomes for Asian patients with X-linked hypophosphataemia : rationale and design of the SUNFLOWER longitudinal, observational cohort study

Introduction X-linked hypophosphataemic rickets/osteomalacia (XLH) is a chronic, debilitating genetic disease characterised by skeletal abnormalities and growth disorder. The burden of XLH begins in childhood and continues throughout life. Conventional medical therapy with phosphate, active vitamin D and surgery do not address the underlying pathophysiology of the disease. While treatment during childhood may improve bone deformity and growth retardation, a large proportion of adult patients still fail to reach normal stature. Furthermore, adult patients with XLH report comorbidities associated with unresolved childhood disease, as well as newly developed disease-related complications and significantly impaired quality of life (QOL). Despite the multiple negative aspects of XLH, Asian consensus statements for diagnosis and management are lacking. Methods and analysis The Study of longitUdinal observatioN For patients with X-Linked hypOphosphataemic rickets/osteomalacia in collaboration With Asian partnERs study is a longitudinal observational cohort study of patients with XLH, designed to determine the medical characteristics and burdens (physical, emotional and financial) of this progressive disease and to evaluate the impact of treatment (including the use of burosumab) on clinical outcomes. The study was initiated in April 2018, and registration will remain open until 30 April 2022. The sample size planned for analyses is 160 patients, consisting of 100 patients in Japan and 60 patients in Korea. Up to 5 years of observation are planned per patient, from enrolment through to April 2023. Prospective and retrospective data will be collected to evaluate variables, including height/growth, rickets severity score, QOL, motor function and biomarkers for phosphate metabolism and bone turnover. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Osaka University, the Ethics Committee of Kyowa Kirin Co and by the Ethics Committee of each participating medical institution. Two interim analyses and associated publications are planned using retrospective and enrolment data at year 1 and results at year 3