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NAGASE HiroakiGraduate School of Medicine / Faculty of Medical SciencesProfessor
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■ Paper- OBJECTIVE: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). METHODS: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. RESULTS: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). CONCLUSIONS: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.Nov. 2024, Journal of the neurological sciences, 466, 123238 - 123238, English, International magazineScientific journal
- INTRODUCTION: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice. METHODS: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023. RESULTS: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age. CONCLUSIONS: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone.Nov. 2024, Brain & development, 46(10) (10), 332 - 338, English, International magazineScientific journal
- Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein-Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD.Mar. 2024, Human genome variation, 11(1) (1), 17 - 17, English, International magazineScientific journal
- Although the causes of neurodevelopmental disorders remain unknown, several environmental risk factors have attracted considerable attention. We conducted a retrospective, longitudinal, population-based cohort study using data from infant health examinations of children born to mothers with pregnancies between April 1, 2014 and March 31, 2016 in Kobe City to identify the perinatal factors associated with neurodevelopmental referrals in 3-year-old children. There were 15,223 and 1283 children in the normal and referral groups, respectively. Neurodevelopmental referrals at the health checkup for 3-year-old children were significantly associated with the lack of social support during pregnancy (adjusted odds ratio [aOR] 1.99, 99% CI 1.14-3.45, p = 0.001), history of psychiatric consultation (aOR 1.56, 99% CI 1.10-2.22, p = 0.001), no social assistance post-delivery (aOR 1.49, 99% CI 1.03-2.16, p = 0.006), Edinburgh Post-natal Depression Scale (EPDS) score ≥ 9 (aOR 1.36, 99% CI 1.01-1.84, p = 0.008), infant gender (male) (aOR 2.51, 99% CI 2.05-3.06, p < 0.001), and cesarean delivery (aOR 1.39, 99% CI 1.11-1.75, p < 0.001). In conclusion, this exploratory study in the general Japanese population identified six perinatal factors associated with neurodevelopmental referrals in 3-year-old children: infant gender (male), cesarean section, maternal history of psychiatric consultation, EPDS score ≥ 9, lack of social support during pregnancy, and no social assistance post-delivery.Feb. 2024, Scientific reports, 14(1) (1), 3492 - 3492, English, International magazineScientific journal
- Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal blood at birth and the correlation between PIVKA-II and gestational age are unclear. We retrospectively analyzed infants admitted to our institution between June 1, 2018, and March 31, 2022, whose clinical and PIVKA-II data were available, and classified them into preterm and term infant groups. Overall incidence of PIVKA-II-positive cases (≥ 50 mAU/mL) was 42.8%, including 0.6% apparent VK deficiency (≥ 5000 mAU/mL), 3.1% experimental VK deficiency (1000-4999 mAU/mL), and 10.7% latent VK deficiency (200-999 mAU/mL) cases. Incidence of PIVKA-II-positive cases was significantly higher in the term group than in the preterm group (49.4% vs. 29.7%, p < 0.001). Gestational age correlated with PIVKA-II levels (r2 = 0.117, p < 0.0001). Median serum PIVKA-II levels and incidence of PIVKA-II-positive cases (≥ 50 mAU/mL, 16.4%) were lower at 5 days after birth than at birth, possibly reflecting the postnatal VK prophylaxis impact. Only one infant was diagnosed with VK deficiency bleeding (PIVKA-II levels, at birth: 10,567 mAU/mL; at day 5: 2418 mAU/mL). Thus, serum PIVKA-II levels after birth weakly correlated with gestational age. VK deficiency was more common in term infants than in preterm infants.Jan. 2024, Scientific reports, 14(1) (1), 921 - 921, English, International magazineScientific journal
- OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. METHODS: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. RESULTS: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. CONCLUSIONS: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.Elsevier BV, Jan. 2024, Journal of the Neurological Sciences, 457, 122867 - 122867, English, International magazineScientific journal
- This study investigated the relationship between sleep habits in early childhood and academic performance and non-cognitive skills in the first grade. We retrospectively analyzed a longitudinal population-based cohort from birth through early childhood, up to elementary school, in Amagasaki City, Japan. The primary outcome was academic performance in the first grade. Other outcomes were self-reported non-cognitive skills. Overall, 4395 children were enrolled. Mean national language scores for children with bedtimes at 18:00-20:00, 21:00, 22:00, and ≥ 23:00 were 71.2 ± 19.7, 69.3 ± 19.4, 68.3 ± 20.1, and 62.5 ± 21.3, respectively. Multiple regression analysis identified bedtime at 3 years as a significant factor associated with academic performance. However, sleep duration was not significantly associated with academic performance. Bedtime at 3 years also affected non-cognitive skills in the first grade. Diligence decreased with a later bedtime (21:00 vs. 18:00-20:00; odds ratio [OR]: 1.98, 95% confidence interval [CI] 1.27-3.09; 22:00 vs. 18:00-20:00; OR: 2.15, 95% CI 1.37-3.38; ≥ 23:00 vs. 18:00-20:00; OR: 2.33, 95% CI 1.29-4.20). Thus, early bedtime at 3 years may be associated with a higher academic performance and better non-cognitive skills in the first grade. Optimum early-childhood sleep habits may positively impact academic future.Nov. 2023, Scientific reports, 13(1) (1), 20926 - 20926, English, International magazineScientific journal
- OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a serious condition that requires intensive care and is associated with a high mortality rate. However, its pathogenesis remains unclear. In the present study, a genetic analysis was performed to determine the genetic background of patients with clinically suspected Dravet syndrome (DS) who developed HSES. METHODS: Whole exome sequencing was performed, followed by minigene analysis of the intron variant detected by whole exome sequencing to confirm its effect on splicing. RESULTS: Whole exome sequencing revealed a novel 21-bp deletion in intron 3 of SCN1A NM_001165963.4 (NC_000002.11:g.166073675_166073695del). This deletion was not found in the patient's parents and was proven to be de novo. Minigene analysis revealed an aberrant mRNA lacking 40 and 106 bp from the 5' end of exon 4 of SCN1A. Therefore, we diagnosed this case as DS due to the deletion in intron 3 of SCN1A. CONCLUSIONS: We report a case of DS with HSES caused by a 21-bp deletion in the intron of SCN1A that was confirmed by minigene analysis. The present case met Levin's criteria for HSES and the splicing analysis of SCN1A is an important finding. This study has important implications for understanding HSES pathogenesis.Jun. 2023, Brain & development, 45(6) (6), 317 - 323, English, International magazineScientific journal
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S302 - S302, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S319 - S319, Japanese
- (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 627 - 627, JapaneseCOVID-19感染症を契機に急性増悪した全身型重症筋無力症の女児例
- Background and objectives To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes. Methods A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge. Results Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01). Discussion Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.Frontiers Media SA, Feb. 2023, Frontiers in Neuroscience, 17, 1085082 - 1085082, English, International magazineScientific journal
- BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.Jan. 2023, BMC neurology, 23(1) (1), 28 - 28, English, International magazineScientific journal
- BACKGROUND: Cytokine levels have been measured in acute encephalopathy (AE) to determine its pathology or as a diagnostic biomarker to distinguish it from febrile seizures (FS); however, the dynamics of cytokine level changes have not yet been fully captured in these two neurological manifestations. Thus, we aimed to explore the time course of serum cytokine level changes within 72 h after onset in AE and FS. METHODS: We retrospectively measured cytokine level in residual serum samples at multiple timepoints in seven children whose final diagnoses were AE or FS. RESULTS: The levels of 13 cytokines appeared to increase immediately after onset and peaked within 12-24 h after onset: interleukin (IL)-1β, IL-4 IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, fibroblast growth factor, granulocyte colony-stimulating factor, interferon gamma, interferon-inducible protein-10, and macrophage chemoattractant protein-1. There were no dynamic changes in the levels of three cytokines (IL-1 receptor agonist, macrophage inflammatory protein-1α, and platelet-derived growth factor-bb) 72 h after onset. Levels of some cytokines decreased to around control levels within 48 h after onset: IL-1β, IL-4, IL-5, IL-17, fibroblast growth factor, and interferon gamma. The levels of most cytokines appeared to be higher in AE, especially in hemorrhagic shock encephalopathy syndrome, than in FS. CONCLUSIONS: Cytokine levels in both AE and FS change dynamically, such as the levels of several cytokines increased within a few hours after onset and decreased at 12-24 h after onset. Therefore, it will be desirable to make clinical decisions regarding the administration of anti-inflammatory therapy in 24 h after onset in AE.Jan. 2023, BMC neurology, 23(1) (1), 7 - 7, English, International magazineScientific journal
- Our goal was to conduct a scoping review of the literature on the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy in children, focusing on treatment targets and treatment initiation timing. We performed literature searches using PubMed for articles reporting treatments of infection-triggered encephalopathy syndrome/acute encephalopathy. We included articles describing specific treatments for acute encephalopathy with control groups. For the purpose of searching new therapies only experimentally tried in the case series, we also included case series studies without control groups in this review, if the studies contained at least two cases with clear treatment goals. Therapies were classified based on their mechanisms of action into brain protection therapy, immunotherapy, and other therapies. We operationally categorized the timing of treatment initiation as T1 (6-12 h), T2 (12-24 h), T3 (24-48 h), and T4 (>48 h) after the onset of seizures and/or impaired consciousness. Thirty articles were included in this review; no randomized control study was found. Eleven retrospective/historical cohort studies and five case-control studies included control groups with or without specific therapies or outcomes. The targeted conditions and treatment timing varied widely across studies. However, the following three points were suggested to be effective in multiple studies: (1) Careful seizure management and targeted temperature management within 12 h (T1) of onset of febrile seizure/prolonged impaired consciousness without multiple organ failure may reduce the development of acute encephalopathy with biphasic seizures and late reduced diffusion; (2) immunotherapy using corticosteroids, tocilizumab, or plasma exchange within 24 h (T1-T2) of onset of acute necrotizing encephalopathy may reduce sequelae; and (3) anakinra therapy and ketogenic diet demonstrate little evidence of neurologic sequelae reduction, but may reduce seizure frequency and allow for weaning from barbiturates, even when administered weeks (T4) after onset in children with febrile infection-related epilepsy syndrome. Although available studies have no solid evidence in the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy, this scoping review lays the groundwork for future prospective clinical trials.2023, Frontiers in neuroscience, 17, 1150868 - 1150868, English, International magazineScientific journal
- Whether neurologic symptoms due to SARS-CoV-2 differ from those of non-SARS-CoV-2 viral infection is unclear. We aimed to describe these neurological manifestations and compare the clinical characteristics and treatments in children with seizures and fever with or without COVID-19. We retrospectively analyzed data from 105 hospitalized children (<18 years) with clinical seizures and fever between September 2021 and August 2022. We compared the clinical characteristics and treatments between the COVID-19 (n = 20) and non-COVID-19 (n = 85) groups. Patients with COVID-19 were older than those without (32.5 [20-86] months vs. 20 [16-32] months, p = 0.029). Seizure type and duration and impaired consciousness duration did not differ between groups. Six and 32 patients experienced status epilepticus lasting 30 min in the COVID-19 and non-COVID-19 groups, respectively. Most treatments did not differ between groups; however, electroencephalography was used less frequently for COVID-19. Neurological sequelae occurred in one and four patients in the COVID-19 and non-COVID-19 groups, respectively. In conclusion, seizures with fever due to SARS-CoV-2 were more common in older children. Seizure characteristics and neurologic sequelae did not differ in children with and those without COVID-19. In general, electroencephalography was used less during COVID-19 for infection control measures.2023, Epilepsy & behavior reports, 24, 100625 - 100625, English, International magazineScientific journal
- Nov. 2022, Brain & development, 44(10) (10), 771 - 772, English, International magazine
- Rotavirus (RV) is the leading cause of acute gastroenteritis (AGE), particularly in infants. In 2006, the high efficacy of oral RV vaccines (RVVs, RotarixTM and RotaTeqTM) was demonstrated. Voluntary RVV started in Japan in 2011, and in October 2020 were launched as universal oral RVVs in Japan. However, the impact of changes from voluntary to universal RVVs has not been studied in a primary emergency medical center in Japan. We investigated changes in the number of pediatric patients with AGE after introducing universal RVVs in our center. A clinical database of consecutive patients aged <16 who presented to Kobe Children's Primary Emergency Medical Center between 1 April 2016 and 30 June 2022 was reviewed. After implementing universal RVVs, fewer children presented with RV-associated AGE (the reduction of proportion of the patients in 2022 was -61.7% (all ages), -57.9% (<1 years), -67.8% (1-<3 years), and -61.4% (3-<5 years) compared to 2019). A similar decrease in those of age who were not covered by the universal RVV was observed. There was a significant decline in the number of patients with AGE during the RV season who presented to the emergency department after implementing universal RVVs.Oct. 2022, Vaccines, 10(11) (11), English, International magazineScientific journal
- Gitelman syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by loss of function in the SLC12A3 gene (NM_000339.2), which encodes the natrium chloride cotransporter. The detection of homozygous or compound heterozygous SLC12A3 variants is expected in GS, but 18%-40% of patients with clinical GS carry only one mutant allele. Previous reports identified some pathogenic deep intronic variants in SLC12A3. Here, we report the screening of SLC12A3 deep intronic variants in 13 patients with suspected GS carrying one mutated SLC12A3 allele. Variant screening used the HaloPlex Target Enrichment System Kit capturing whole introns and the promotor region of SLC12A3, followed by SureCall variant analysis. Rare intronic variants (<1% frequency) were identified, and pathogenicity evaluated by the minigene system. Deep intronic variant screening detected seven rare SLC12A3 variants from six patients. Only one variant showed pathogenicity in the minigene system (c.602-16G>A, intron 4) through activation of a cryptic acceptor site. No variants were detected in the promotor region. Deep intronic screening identified only one pathogenic variant in patients with suspected GS carrying monoallelic SLC12A3 variants. Our results suggest that deep intronic variants partially explain the cause of monoallelic variants in patients with GS.Sep. 2022, American journal of medical genetics. Part A, 188(9) (9), 2576 - 2583, English, International magazineScientific journal
- American Society of Nephrology ({ASN}), May 2022, Kidney360, 3(8) (8), 1384 - 1393, English, International magazine[Refereed]Scientific journal
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S210 - S210, Japanese
- Background: Alport syndrome is an inherited disorder characterized by progressive renal disease, variable sensorineural hearing loss, and ocular abnormalities. Although many pathogenic variants in COL4A3 and COL4A4 have been identified in patients with autosomal Alport syndrome, synonymous mutations in these genes have rarely been identified. Methods: We conducted in silico splicing analysis using Human Splicing Finder (HSF) and Alamut to predict splicing domain strength and disruption of the sites. Furthermore, we performed in vitro splicing assays using minigene constructs and mRNA analysis of patient samples to determine the pathogenicity of four synonymous variants detected in four patients with suspected autosomal dominant Alport syndrome (COL4A3 [c.693G>A (p.Val231=)] and COL4A4 [c.1353C>T (p.Gly451=), c.735G>A (p.Pro245=), and c.870G>A (p.Lys290=)]). Results: Both in vivo and in vitro splicing assays showed exon skipping in two out of the four synonymous variants identified (c.735G>A and c.870G>A in COL4A4). Prediction analysis of wild-type and mutated COL4A4 sequences using HSF and Alamut suggested these two variants may lead to the loss of binding sites for several splicing factors, e.g., in acceptor sites and exonic splicing enhancers. The other two variants did not induce aberrant splicing. Conclusions: This study highlights the pitfalls of classifying the functional consequences of variants by a simple approach. Certain synonymous variants, although they do not alter the amino acid sequence of the encoded protein, can dramatically affect pre-mRNA splicing, as shown in two of our patients. Our findings indicate that transcript analysis should be carried out to evaluate synonymous variants detected in patients with autosomal dominant Alport syndrome.Mar. 2022, Kidney360, 3(3) (3), 497 - 505, English, International magazineScientific journal
- Vital signs are important for patient assessment, but little is known about interpreting those of children in prehospital settings. We conducted an observational study to investigate the association between prehospital vital signs of children and their clinical outcomes in hospitals. We plotted the data of patients with critical outcomes on published reference ranges, such as those of healthy children to evaluate the clinical relevance. Of the 18,493 children screened, 4477 transported to tertiary hospitals were included in the analysis. The outcomes 12 h after being transported to a tertiary hospital were as follows: deceased, 41; hospitalization with critical deterioration events, 65; hospitalization without critical deterioration events, 1086; returned home, 3090; and unknown, 195. The reference ranges of the heart rates (sensitivity: 57.7%, specificity: 67.5%) and respiratory rates (sensitivity: 54.5%, specificity: 67.7%) of healthy children worked best to detect the critical outcomes. Therefore, the reference ranges of healthy children were concluded to be suitable in prehospital settings; however, excessive reliance on vital signs carried potential risks due to their limited sensitivities and specificities. Future studies are warranted to investigate indicators with higher sensitivities and specificities.Mar. 2022, Scientific reports, 12(1) (1), 5199 - 5199, English, International magazineScientific journal
- Behavioral Therapy for Children with Avoidant/Restrictive Food Intake Disorder Dependent on Tube or Oral Enteral Nutrient Formula: A Feasibility Study.In children with eating disorders, nutritional status and growth may depend on enteral nutrient formula. Ultimately, its goal is to introduce or reintroduce oral feeding. Japanese research on the treatment of tube or oral formula-dependent children is scarce. This study determined the feasibility of behavioral therapy for children with avoidant/restrictive food intake disorder and dependency on the tube or oral enteral nutrient formula in Japan. Medical records of children diagnosed with this disorder, dependent on the tube or oral enteral nutrient formula and who had received behavioral therapy intervention to withdraw from the formula were retrospectively investigated. We collected their characteristics at first visit and the caloric percentage from oral food intake six months after starting the treatment. In total, four patients (age range: 2-5 years) participated in this study. The feeding routes employed before the intervention were a nasogastric tube for one patient, a gastrostomy bottom for the other patient, and oral formula for the remaining patients (i.e., two children). At the sixth month of the behavioral treatment, none of the patients needed the formula, and the caloric percentage of required nutrition from oral food intake was 100%. Our data demonstrate that this behavioral therapy is feasible for children with avoidant/restrictive food intake disorder dependent on the tube or oral formula in Japan.Mar. 2022, The Kobe journal of medical sciences, 67(4) (4), E155-E160, English, Domestic magazineScientific journal
- BACKGROUND: Febrile status epilepticus is the most common form of status epilepticus in children. No previous reports compare the effectiveness of treatment strategies using fosphenytoin (fPHT) or phenobarbital (PB) and those using anesthetics as second-line anti-seizure medication for benzodiazepine-resistant convulsive status epilepticus (CSE). We aimed to examine the outcomes of various treatment strategies for febrile convulsive status epilepticus (FCSE) in a real-world setting while comparing the effects of different treatment protocols and their presence or absence. METHODS: This was a single-center historical cohort study that was divided into three periods. Patients who presented with febrile convulsive status epilepticus for ≥60 min even after the administration of at least one anticonvulsant were included. During period I (October 2002-December 2006), treatment was performed at the discretion of the attending physician, without a protocol. During period II (January 2007-February 2013), barbiturate coma therapy (BCT) was indicated for FCSE resistant to benzodiazepines. During period III (March 2013-April 2016), BCT was indicated for FCSE resistant to fPHT or PB. RESULTS: The rate of electroencephalogram monitoring was lower in period I than period II+III (11.5% vs. 85.7%, p<0.01). Midazolam was administered by continuous infusion more often in period I than period II+III (84.6% vs. 25.0%, p<0.01), whereas fPHT was administered less often in period I than period II+III (0% vs. 27.4%, p<0.01). The rate of poor outcome, which was determined using the Pediatric Cerebral Performance Category scale, was higher in period I than period II+III (23.1% vs. 7.1%, p=0.03). The rate of poor outcome did not differ between periods II and III (4.2% vs. 11.1%, p=0.40). CONCLUSIONS: While the presence of a treatment protocol for FCSE in children may improve outcomes, a treatment protocol using fPHT or PB may not be associated with better outcomes.Mar. 2022, BMC neurology, 22(1) (1), 77 - 77, English, International magazineScientific journal
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 552 - 552, Japanese神戸市東部療育センター診療所の開所後3年間のまとめ
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 557 - 557, Japanese小児科医の意識調査 大事にする価値観は?兵庫県で次に取り組むべき課題は?
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 545 - 545, Japanese初回発症時にMASを合併した若年性特発性若年性関節炎の1例
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 551 - 551, Japanese過去5年間の小児摂食障害に対する家族療法の経験
- (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 552 - 552, Japanese神戸市東部療育センター診療所の開所後3年間のまとめ
- OBJECTIVE: Biomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset. METHODS: We enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years. RESULTS: In the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6-12 h), and 2,411 (12-24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL). CONCLUSIONS: This study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.Mar. 2022, Brain & development, 44(3) (3), 210 - 220, English, International magazineScientific journal
- (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 308 - 308, Japanese一次急病施設における異物・毒物誤飲診療の現状と課題
- BACKGROUND: Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal syndrome of Lowe (OCRL) mutations, their clinical severities differ substantially and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1-7 lead to Dent disease-2, whereas those in exons 8-24 lead to Lowe syndrome. Herein we identified the mechanism underlying the action of novel OCRL protein isoforms. METHODS: Messenger RNA samples extracted from cultured urine-derived cells from a healthy control and a Dent disease-2 patient were examined to detect the 5' end of the OCRL isoform. For protein expression and functional analysis, vectors containing the full-length OCRL transcripts, the isoform transcripts and transcripts with truncating mutations detected in Lowe syndrome and Dent disease-2 patients were transfected into HeLa cells. RESULTS: We successfully cloned the novel isoform transcripts from OCRL exons 6-24, including the translation-initiation codons present in exon 8. In vitro protein-expression analysis detected proteins of two different sizes (105 and 80 kDa) translated from full-length OCRL, whereas only one protein (80 kDa) was found from the isoform and Dent disease-2 variants. No protein expression was observed for the Lowe syndrome variants. The isoform enzyme activity was equivalent to that of full-length OCRL; the Dent disease-2 variants retained >50% enzyme activity, whereas the Lowe syndrome variants retained <20% activity. CONCLUSIONS: We elucidated the molecular mechanism underlying the two different phenotypes in OCRL-related diseases; the functional OCRL isoform translated starting at exon 8 was associated with this mechanism.Jan. 2022, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 37(2) (2), 262 - 270, English, International magazineScientific journal
- INTRODUCTION: Previous studies reported a dramatic decline in the incidence of varicella and varicella-related deaths after implementing universal varicella vaccination (VarV). Although previous studies reported the effectiveness and economic impact of VarV, they were unknown in the emergency department (ED) setting. METHODS: To determine the effectiveness and economic impact of VarV in the ED, Kobe, Japan, we retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED from 2011 to 2019. RESULTS: Of the 265,191 children presenting to our ED, 3,092 patients were clinically diagnosed with varicella. The number of patients with varicella was approximately 500 annually, before introducing the universal two-dose VarV for children aged 1 to <3 years in October 2014, in the Japanese national immunization program, and decreased to approximately 200 in 2019. The number of patients with varicella younger than 1 year (ineligible for the vaccination) also decreased. Regarding the economic impact, the medical cost in our ED reduced after the introduction of VarV was JPY 4.1 million (US$ 40,049) annually. From the central data, approximately 95% of children were vaccinated after October 2014; however, a relatively large percentage of infected unvaccinated children (59.0%) presented to ED in this study. After the implementation of the universal VarV, infection was mainly observed in older children (i.e., the unvaccinated generation). CONCLUSIONS: Our data showed the effectiveness and economic impact of VarV in the ED setting. Additionally, our data suggested that the public vaccination program should include older unvaccinated children and other unvaccinated individuals.Jan. 2022, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 28(1) (1), 35 - 40, English, International magazineScientific journal
- Introduction: COL4A5 is a causative gene of X-linked Alport syndrome (XLAS). Male patients with XLAS with nonsense variants have the most severe phenotypes of early onset end-stage kidney disease (ESKD); those with splicing variants have middle phenotypes and those with missense variants have the mildest phenotypes. Therefore, genotyping for male patients with XLAS can be used to predict kidney prognosis. Single-base substitutions at the last nucleotide position in each exon are known to affect splicing patterns and could be splicing variants. Nevertheless, in XLAS, these variants are generally considered to be missense variants, without conducting a transcript analysis, which underestimates some patients as having mild phenotypes. This study aimed to investigate whether single-base substitutions at the last nucleotide position of COL4A5 exons cause aberrant splicing. Methods: In total, 20 variants were found in the Human Gene Mutation Database (n = 14) and our cohort (n = 6). We performed functional splicing assays using a hybrid minigene analysis and in vivo transcript analyses of patients' samples when available. Then, we investigated genotype-phenotype correlations for patients with splicing variants detected in this study by comparing data from our previous studies. Results: Among the 20 variants, 17 (85%) caused aberrant splicing. Male patients with splicing variants had more severe phenotypes when compared with those with missense variants. Findings from the in vivo analyses for 3 variants were identical to those from the minigene assay. Conclusion: Our study revealed that most single-base substitutions at the last nucleotide position of COL4A5 exons result in splicing variants, rather than missense variants, thereby leading to more severe phenotypes.Jan. 2022, Kidney international reports, 7(1) (1), 108 - 116, English, International magazineScientific journal
- (株)総合医学社, Dec. 2021, 小児科臨床, 74(増刊) (増刊), 1812 - 1821, Japanese
- BACKGROUND: An unprovoked seizure is a seizure or a cluster of seizures occurring within 24 h in a patient older than 1 month of age without precipitating factors. Recent studies have reported that extrinsic factors, such as meteorological conditions and air pollutants, may be important in seizure occurrence. Thus, this study aimed to examine the association between the number of visits to the emergency department (ED) by children for nighttime unprovoked seizures and exposure to multi-faceted factors, such as meteorological conditions and air pollution. METHODS: We conducted a clinical observational analysis and reviewed consecutive patients younger than 16 years of age who visited the primary ED center in Kobe City, Japan, during nighttime (7:30 p.m.-7:00 a.m.) between January 1, 2011 and December 31, 2015. We investigated the effects of meteorological factors and air pollutants on the number of patients with unprovoked seizures using multivariate analysis of Poisson regression estimates. RESULTS: In total, 151,119 children visited the ED, out of which 97 patients presented with unprovoked seizures. The mean age of the patients was 4.7 years (range, 1 month to 15.3 years), and 54.6% of them were boys. The total number of patients with unprovoked seizures showed no significant changes with the seasons; however, there were dominant peaks during the fall and fewer visits during the summer. The multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients presenting with unprovoked seizures and precipitation (+1 patient/87 mm; p = 0.03) and methane (+1 patient/0.14 ppm; p = 0.03) levels and a negative relationship between the number of patients presenting with unprovoked seizures and nitrogen dioxide level (-1 patient/0.02 ppm; p = 0.04). CONCLUSIONS: The present study is the first to evaluate the association between the number of children who presented to the ED with nighttime unprovoked seizures and environmental factors after controlling for confounding factors.Dec. 2021, Epilepsy & behavior : E&B, 125, 108434 - 108434, English, International magazineScientific journal
- The coronavirus disease (COVID-19) pandemic altered environmental factors. We studied the impact of these changes on asthma exacerbation (AE) by comparing the AE-related environmental factors between COVID-19 (2020) and pre-COVID-19 (2011-2019) eras. Between 2011 and 2020, 278,465 children (<16 years old) visited our emergency department, and 7476 were diagnosed with AE. The number of patients showed spring and fall peaks in 2011-2019. Multivariate analyses showed significant positive relationships of the number of AE patients with the average temperature among all patients and 0-5-year-olds and with sulfur dioxide (SO2) levels in 2011-2019 among 0-5-year-olds. Although the spring peak in the number of patients was not observed in 2020 after declaration of a state of emergency, the fall peak was again observed after the state of emergency was lifted. No changes in average temperature were detected, but SO2 was significantly reduced following declaration of the state of emergency in 2020. Therefore, SO2 reduction might have contributed to the disappearance of the peak of AE. However, a fall peak was observed again in 2020, although SO2 levels continued to be low. These data suggest that person to person interaction seems to be associated with AE, presumably due to unknown viral infections.Oct. 2021, International journal of environmental research and public health, 18(21) (21), English, International magazineScientific journal
- Background: Pathogenic variants in single genes encoding podocyte-associated proteins have been implicated in about 30% of steroid resistant nephrotic syndrome (SRNS) patients in children. However, LAMA5 gene biallelic variants have been identified in only 7 patients so far, and most are missense variants of unknown significance. Furthermore, no functional analysis had been conducted for all but one of these variants. Here, we report three patients with LAMA5 gene biallelic truncating variants manifesting infantile nephrotic syndrome and one SRNS case with biallelic LAMA5 missense variants. Methods: We conducted comprehensive gene screening of Japanese patients with severe proteinuria. Using targeted next-generation sequencing, 62 podocyte-related genes were screened in 407 unrelated patients with proteinuria. For the newly discovered LAMA5 variants, we conducted in vitro heterotrimer formation assays. Results: Biallelic truncating variants in the LAMA5 gene (NM_005560) were detected in 3 patients from 2 families. All patients presented with proteinuria within 6 months of age. Patients 1 and 2 were siblings possessing a nonsense variant (c.9232C>T, p.(Arg3078*)) and a splice site variant (c.1282+1G>A) that led to exon 9 skipping and a frameshift. Patient 3 had a remarkable irregular contour of the glomerular basement membrane. She was subsequently found to have a nonsense variant (c.8185C>T, p.(Arg2720*)) and the same splice site variant in patients 1 and 2. By in vitro heterotrimer formation assays, both truncating variants produced smaller laminin α5 proteins that nevertheless formed trimers with laminin β1 and γ1 chains. Patient 4 showed SRNS at the age of eight and carried compound heterozygous missense variants (c.1493C>T, p.(Ala498Val) and c.8399G>A, p.(Arg2800His)). Conclusions: Our patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome. We also discerned the clinical and pathological characteristics observed in LAMA5-related nephropathy. LAMA5 variant screening should be performed in congenital/infantile nephrotic syndrome patients.American Society of Nephrology (ASN), Oct. 2021, Kidney360, 2(12) (12), 10.34067/KID.0004952021 - 10.34067/KID.0004952021, English, International magazineScientific journal
- Introduction: Frasier syndrome (FS) is a rare inherited kidney disease caused by intron 9 splicing variants of WT1. For wild-type WT1, 2 active splice donor sites in intron 9 cause a mixture of 2 essential transcripts (with or without lysine-threonine-serine [+/KTS or -KTS]), and imbalance of the +KTS/-KTS ratio results in the development of FS. To date, 6 causative intron 9 variants have been identified; however, detailed transcript analysis has not yet been conducted and the genotype-phenotype correlation also remains to be elucidated. Methods: We conducted an in vitro minigene splicing assay for 6 reported causative variants and in vivo RNA sequencing to determine the +KTS/-KTS ratio using patients' samples. We also performed a systematic review of reported FS cases with a description of the renal phenotype. Results: The in vitro assay revealed that although all mutant alleles produced -KTS transcripts only, the wild-type allele produced both +KTS and -KTS transcripts at a 1:1 ratio. In vivo RNA sequencing showed that patients' samples with all heterozygous variants produced similar ratios of +KTS to -KTS (1:3.2-1:3.5) and wild-type kidney showed almost a 1:1 ratio (1:0.85). A systematic review of 126 cases clarified that the median age of developing ESKD was 16 years in all FS patients, and there were no statistically significant differences between the genotypes or sex chromosome karyotypes in terms of the renal survival period. Conclusion: Our study suggested no differences in splicing pattern or renal survival period among reported intron 9 variants causative of FS.Oct. 2021, Kidney international reports, 6(10) (10), 2585 - 2593, English, International magazineScientific journal
- OBJECTIVES: Accidental foreign body ingestion (FBI) and toxic agent ingestion (TAI) are commonly encountered among children in primary emergency settings. Early detection and appropriate medical intervention are crucial to improve outcomes. Although many reports from tertiary institutions have shown improvements in therapy, data are still lacking from primary emergency facilities. METHODS: We performed a retrospective analysis based on medical records of FBI/TAI over 4 years at the Kobe Children's Primary Emergency Medical Center. We collected patient information, including age, sex, time between FBI/TAI occurrence and centre visit, provision of first aid, symptoms, type of FBI/TAI, examinations, treatments, and outcomes. RESULTS: A total of 580 children were enrolled. The median age was 1.3 years, and patients under 2 years old accounted for 70% of total cases. Cigarettes (17.5%) were the most common ingested foreign body, followed by medicines (15.3%), detergents (8.1%), in TAI, plastics (14.1%), metal (13.4%), batteries (9.0%) in FBI, and others (22.6%). A total of 42 patients were transferred to advanced hospitals; among these, 22 patients were hospitalised but the foreign body was removed in only 3 (0.9%) patients. Transferred patients were significantly older (P<0.05) in FBI and had a higher rate of any of symptoms (P<0.05) in FBI/TAI. CONCLUSIONS: This large-scale retrospective study of accidental FBI/TAI conducted at a primary emergency facility clarified current management, including treatment at a primary facility. Very few cases of FBI/TAI were treated, even when they were transferred to an advanced treatment hospital. Unified protocols should be established, to improve the management of FBI/TAI.Sep. 2021, Minerva pediatrics, English, International magazineScientific journal
- Gitelman syndrome is an autosomal recessive inherited salt-losing tubulopathy. It has a prevalence of around 1 in 40,000 people, and heterozygous carriers are estimated at approximately 1%, although the exact prevalence is unknown. We estimated the predicted prevalence of Gitelman syndrome based on multiple genome databases, HGVD and jMorp for the Japanese population and gnomAD for other ethnicities, and included all 274 pathogenic missense or nonsense variants registered in HGMD Professional. The frequencies of all these alleles were summed to calculate the total variant allele frequency in SLC12A3. The carrier frequency and the disease prevalence were assumed to be twice and the square of the total allele frequency, respectively, according to the Hardy-Weinberg principle. In the Japanese population, the total carrier frequencies were 0.0948 (9.5%) and 0.0868 (8.7%) and the calculated prevalence was 0.00225 (2.3 in 1000 people) and 0.00188 (1.9 in 1000 people) in HGVD and jMorp, respectively. Other ethnicities showed a prevalence varying from 0.000012 to 0.00083. These findings indicate that the prevalence of Gitelman syndrome in the Japanese population is higher than expected and that some other ethnicities also have a higher prevalence than has previously been considered.Aug. 2021, Scientific reports, 11(1) (1), 16099 - 16099, English, International magazineScientific journal
- ABSTRACT: Steroid pulse therapy is widely used to treat virus-associated acute encephalopathy, especially the cytokine storm type; however, its effectiveness remains unknown. We sought to investigate the effectiveness of early steroid pulse therapy for suspected acute encephalopathy in the presence of elevated aspartate aminotransferase (AST) levels.We enrolled children admitted to Hyogo Children's Hospital between 2003 and 2017 with convulsions or impaired consciousness accompanied by fever (temperature >38°C). The inclusion criteria were: refractory status epilepticus or prolonged neurological abnormality or hemiplegia at 6 hours from onset, and AST elevation >90 IU/L within 6 hours of onset. We excluded patients with a neurological history. We compared the prognosis between the groups with or without steroid pulse therapy within 24 hours. A good prognosis was defined as a Pediatric Cerebral Performance Category Scale (PCPC) score of 1-2 at the last evaluation, within 30 months of onset. Moreover, we analyzed the relationship between prognosis and time from onset to steroid pulse therapy.Fifteen patients with acute encephalopathy and 5 patients with febrile seizures were included in this study. Thirteen patients received steroid pulse therapy within 24 hours. There was no between-group difference in the proportion with a good prognosis. There was no significant correlation between PCPC and timing of steroid pulse therapy (rs = 0.253, P = .405). Even after excluding 2 patients with brainstem lesions, no significant correlation between PCPC and steroid pulse therapy timing (rs = 0.583, P = .060) was noted. However, the prognosis tended to be better in patients who received steroid pulse therapy earlier.Steroid pulse therapy within 24 hours did not improve the prognosis in children with suspected acute encephalopathy associated with elevated AST. Still, even earlier administration of treatment could prevent the possible neurological sequelae of this condition.Jul. 2021, Medicine, 100(30) (30), e26660, English, International magazineScientific journal
- Introduction: WT1 missense mutation in exon 8 or 9 causes infantile nephrotic syndrome with early progression to end-stage kidney disease (ESKD), Wilms tumor, and 46,XY female. However, some patients with missense mutations in exon 8 or 9 progress to ESKD in their teens or later. Therefore, we conducted a systematic review and functional analysis of WT1 transcriptional activity. Methods: We conducted a systematic review of 174 cases with WT1 exon 8 or 9 missense variants from our cohort (n=13) and previous reports (n=161). Of these cases, mild and severe genotypes were selected for further in vitro functional analysis using luciferase assay. Results: The median age of developing ESKD was 1.17 years. A comparative study was conducted among three WT1 genotype classes: mutations of the DNA-binding site (DBS group), mutations outside the DNA-binding site but at sites important for zinc finger structure formation by 2 cysteines and 2 histidines (C2H2 group), and mutations leading to other amino acid changes (Others group). The DBS group showed the severest phenotype and the C2H2 group was intermediate, whereas the Others group showed the mildest phenotype (developing ESKD at 0.90, 2.00, and 3.92 years, respectively, with significant differences). In vitro functional analysis showed dominant-negative effects for all variants; in addition, the DBS and C2H2 mutations were associated with significantly lower WT1 transcriptional activity than the other mutations. Conclusion: Not only the DNA-binding site but also C2H2 zinc finger structure sites are important for maintaining WT1 transcriptional activity, and their mutation causes severe clinical symptoms.Elsevier BV, May 2021, Kidney International Reports, 6(8) (8), 2114 - 2121, English, International magazineScientific journal
- OBJECTIVES: To examine the association between the number of visits to the emergency department (ED) by children for night-time headaches and exposure to multifaceted factors, such as meteorological conditions and air pollution. DESIGN: We conducted a clinical observational time-series analysis study. SETTING: We reviewed consecutive patients younger than 16 years of age at the primary ED centre in Kobe city, Japan, during the night shift (19:30-7:00 hours) between 1 January 2011 and 31 December 2019. PARTICIPANTS: In total, 265 191 children visited the ED; 822 presented with headache during the study period. PRIMARY OUTCOME MEASURES: We investigated the effects of meteorological factors and air pollutants by multivariate analysis of Poisson regression estimates. A subanalysis included the relationship between the number of patients with night-time headaches and the above factors by sex. Furthermore, the effect of typhoon landing on patient visits for headache was also analysed. Headache was not classified because examinations were performed by general paediatricians (non-specialists). RESULTS: The number of patients with night-time headaches displayed distinct seasonal changes, with peaks during the summer. Multivariate analysis of Poisson regression estimates revealed a significant positive relationship between the number of patients for headache and mean temperature. Subanalysis by sex indicated a positive relationship between the number of patients with headache and mean temperature in both sexes; however, it was significant only for females. No relationship was found between the number of patients with headache and air pollution. There was no change in the number of patients for night-time headaches 3 days before and after typhoon landing. CONCLUSIONS: High temperature is the main factor for visiting ED for night-time headaches among children in Kobe city. Our results suggest that preventive measures against night-time headaches may be possible by reducing time spent outside during summer.Apr. 2021, BMJ open, 11(4) (4), e046520, English, International magazineScientific journal
- INTRODUCTION: Children with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes. METHODS: We studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children's Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS. RESULTS: Of the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013). CONCLUSION: The occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.Apr. 2021, Brain & development, 43(4) (4), 548 - 555, English, International magazine[Refereed]Scientific journal
- Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for UGT1A1*28 (c.-41-40dup), UGT1A1*6 (c.211 G > A), and UGT1A1*27 (c.686 C > A). The allele frequency of UGT1A1*6 (OR = 1.34, p = 0.26) and UGT1A1*28 (OR = 0.80, p = 0.54) and the prevalence of UGT1A1*28/*6 diplotypes did not differ significantly from those in the control population. No UGT1A1*27 allele was detected in the subjects. ASD symptom assessment scores were not associated with UGT1A1*28/*6/*27 genotypes or UGT1A1*28/*6 diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.Mar. 2021, Journal of autism and developmental disorders, 52(2) (2), 483 - 489, English, International magazineScientific journal
- ANGUSTIFOLIA (AN) is a plant-specific subfamily of the CtBP/BARS/AN family, characterized by a plant-specific C-terminal domain of approximately 200 amino acids. Previously, we revealed that double knockout (DKO) lines of Physcomitrium (Physcomitrella) patens ANGUSTIFOLIA genes (PpAN1-1 and PpAN1-2) show defects in gametophore height and the lengths of the seta and foot region of sporophytes, by reduced cell elongation. In addition to two canonical ANs, the genome of P. patens has two atypical ANs without a coding region for a plant-specific C-terminus (PpAN2-1 and PpAN2-2); these were investigated in this study. Similar to PpAN1s, both promoters of the PpAN2 genes were highly active in the stems of haploid gametophores and in the middle-to-basal region of young diploid sporophytes that develop into the seta and foot. Analyses of PpAN2-1/2-2 DKO and PpAN quadruple knockout (QKO) lines implied that these four AN genes have partially redundant functions to regulate cell elongation in their expression regions. Transgenic strains harboring P. patens α-tubulin fused to green fluorescent protein, which were generated from a QKO line, showed that the orientation of the microtubules in the gametophore tips in the PpAN QKO lines was unchanged from the wild-type and PpAN1-1/1-2 DKO plants. In addition to both PpAN2-1 and PpAN2-2, short Arabidopsis AN without the C-terminus of 200 amino acids could rescue the Arabidopsis thaliana an-1 phenotypes, implying AN activity is dependent on the N-terminal regions.Mar. 2021, The Plant journal : for cell and molecular biology, 105(5) (5), 1390 - 1399, English, International magazineScientific journal
- OBJECTIVE: The clinical prediction rule (CPR) for acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was developed with an area under the receiver operating characteristic curve (AUC) of 0.95 - 0.96. Our objective was to verify the AESD CPR in a new cohort and compare the utilities of three CPRs of acute encephalopathy: the Tada, Yokochi, and Nagase criteria. METHODS: We reviewed the clinical data and medical charts of 580 consecutive patients (aged < 18 years) with febrile convulsive status epilepticus lasting for ≥ 30 min in 2002 - 2017 and measured the performance of the CPRs in predicting AESD and sequelae. RESULTS: The CPRs predicted AESD with an AUC of 0.84 - 0.88. The Tada criteria predicted AESD with a positive predictive value (PPV) of 0.25 and a negative predictive value (NPV) of 0.99. The Yokochi criteria predicted AESD with a PPV and NPV of 0.20 and 0.95, respectively, after 12 h. The Nagase criteria predicted AESD with a PPV and NPV of 0.14 and 1.00, respectively, after 6 h. The PPVs of the Tada, Yokochi, and Nagase criteria for sequelae were 0.28, 0.28, and 0.17, respectively; the corresponding NPVs were 0.97, 0.95, and 0.98, respectively. CONCLUSIONS: The effectiveness of the AESD CPR in a new cohort was lower than that in the derivation study. CPRs are not sufficient as diagnostic tests, but they are useful as screening tests. The Nagase criteria are the most effective for screening among the three CPRs due to their high NPV and swiftness.Last, Feb. 2021, Brain & development, 43(5) (5), 616 - 625, English, International magazine[Refereed]Scientific journal
- (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 273 - 273, Japanese3歳児健診における発達通過状況とけいれん既往との関連
- Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.Last, Jan. 2021, Cytokine, 137, 155324 - 155324, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene. In 1984, Scheinberg and Sternlieb estimated the prevalence of WD to be 1:30,000. However, recent epidemiological studies have reported increasing prevalence rates in different populations. The carrier frequency of ATP7B variants and the prevalence of WD in the Japanese population have not been reported using multiple databases. METHODS: Multiple public databases were used. First, we included mutations in the ATP7B gene that were registered in the Human Gene Mutation Database (HGMD) Professional, where 885 ATP7B variants were identified as pathogenic. Next, we investigated the allele frequencies of these 885 variants in Japanese individuals using the Human Genetic Variation Database (HGVD) and the Japanese Multi Omics Reference Panel (jMorp). RESULTS: Of the 885 variants of ATP7B, 7 and 12 missense and nonsense variants, 0 and 3 splicing variants, and 0 and 2 small deletions were found in the HGVD and in jMorp, respectively. The total allele frequencies of the ATP7B mutations were 0.011 in the HGVD and 0.014 in the jMorp. According to these data, the carrier frequencies were 0.022 (2.2%) and 0.028 (2.8%), respectively, and patient frequencies were 0.000121 (1.21/10,000 individuals) and 0.000196 (1.96/10,000 individuals), respectively. CONCLUSION: This is the first study to report the carrier frequency of ATP7B variants and the prevalence of WD in Japan using multiple databases. The calculated prevalence of WD was comparatively higher than that of previous reports, indicating previous underdiagnosis or the existence of less severe phenotypes.Dec. 2020, Pediatrics international : official journal of the Japan Pediatric Society, 63(8) (8), 918 - 922, English, International magazine[Refereed]Scientific journal
- OBJECTIVE: To investigate the prevalence of seizures/febrile seizures in children up to 3 years of age and examine the effects of gestational age at birth on the risk for febrile seizures. DESIGN: Retrospective longitudinal population-based cohort study. SETTING: Kobe City public health center, Kobe, Japan, from 2010 to 2018. PARTICIPANTS: Children who underwent a medical check-up at 3 years of age. METHODS: Information regarding seizures was collected from the parents of 96 014 children. We identified the occurrence of seizure/febrile seizure in 74 017 children, whose gestational ages at birth were noted. We conducted a multivariate analysis with the parameter, gestational age at birth, to analyse the risk of seizure. We also stratified the samples by sex and birth weight (<2500 g or not) and compared the prevalence of seizure between those with the term and late preterm births. RESULTS: The prevalence of seizure was 12.1% (11.8%-12.3%), 13.2% (12.2%-14.4%), 14.6% (12.4%-17.7%) and 15.7% (10.5%-22.8%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. The prevalence of febrile seizures was 9.0% (8.8%-9.2%), 10.5% (9.5%-11.5%), 11.8% (9.7%-14.5%) and 11.2% (6.9%-17.7%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. Male was an independent risk factor for seizures (OR: 1.15, 95% CI 1.09 to 1.20; absolute risk increase 0.014, 95% CI 0.010 to 0.019) and febrile seizures (OR: 1.21, 95% CI 1.15 to 1.28; absolute risk increase 0.016, 95% CI 0.012 to 0.020), respectively. Late preterm birth was not associated with an increased risk of seizure/febrile seizure. CONCLUSIONS: Although very preterm birth may increase the risk of seizure/febrile seizure, the risk associated with late preterm birth is considerably small and less than that associated with male.Last, Sep. 2020, BMJ open, 10(9) (9), e035977, English, International magazine[Refereed]Scientific journal
- Galactose-deficient IgA1 (Gd-IgA1) is important in the pathogenesis of IgA nephropathy (IgAN). A Gd-IgA1-specific monoclonal antibody (KM55) has revealed glomerular Gd-IgA1 deposition solely in patients with IgAN and IgA vasculitis with nephritis (IgAV-N). However, this specificity is controversial and has not been demonstrated in pediatric patients. Here, we conducted double-immunofluorescence staining of IgA and Gd-IgA1 in 60 pediatric patients with various glomerular diseases. We divided patients into four groups: (1) patients with IgAN and IgAV-N (n = 23); (2) patients with immunocomplex-mediated glomerulonephritis accompanied by IgA deposition, including lupus nephritis, membranoproliferative glomerulonephritis, and membranous nephropathy (n = 14); (3) patients with other glomerular diseases involving IgA deposition, including idiopathic nephrotic syndrome (INS), oligomeganephronia, Alport syndrome, dense deposit disease, and crescentic glomerulonephritis (n = 11); and (4) patients with IgA-negative diseases including INS, membranoproliferative glomerulonephritis, membranous nephropathy, oligomeganephronia, Alport syndrome, C3 glomerulonephritis, poststreptococcal acute glomerulonephritis, and hemolytic uremic syndrome (n = 12). KM55 staining revealed Gd-IgA1-positive findings in 23/23 patients in Group 1 and 13/14 patients in Group 2, but not in patients in Groups 3 or 4. Therefore, KM55 may detect incidental IgA deposition in pediatric patients. Gd-IgA1 may be involved in the pathogenesis of these immune-related diseases; alternatively, KM55 may recognize IgA-related immunocomplexes in a non-specific manner.Aug. 2020, Scientific reports, 10(1) (1), 14026 - 14026, English, International magazine[Refereed]Scientific journal
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S300 - S300, Japanese
- BACKGROUND: We previously reported the nationwide, epidemiological data of acute encephalopathy in Japan during 2007-2010. Here we conducted the second national survey of acute encephalopathy during 2014-2017, and compared the results between the two studies to elucidate the trends in the seven years' interval as well as the influence of changes in pediatric viral infections and guidelines for acute encephalopathy in Japan. METHODS: The Research Committee on Acute Encephalopathy supported by the Japanese Government sent a questionnaire to 507 hospitals throughout Japan, and collected the responses by mail. RESULTS: A total of 1115 cases from 267 hospitals reportedly had acute encephalopathy during April 2014-June 2017. In this study, the age at onset was younger, the ratios of recently established syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), were higher, and the ratio of influenza-associated encephalopathy was lower, than in the previous study. The age at onset of influenza-associated encephalopathy was lower, and that of HHV-6/7-associated encephalopathy higher, compared to the first survey. The outcomes of entire acute encephalopathy remained unchanged. CONCLUSION: Some of these changes reflected the recent trends of viral infectious diseases including 2009 influenza pandemic, and others the standardization of the diagnosis of acute encephalopathy in Japan.Aug. 2020, Brain & development, 42(7) (7), 508 - 514, English, International magazine[Refereed]Scientific journal
- BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive, hereditary glomerular nephritis of variable severity caused by pathogenic COL4A5 variants. Currently, genetic testing is widely used for diagnosing XLAS; however, determining the pathogenicity of variants detected by such analyses can be difficult. Intronic variants or synonymous variants may cause inherited diseases by inducing aberrant splicing. Transcript analysis is necessary to confirm the pathogenicity of such variants, but it is sometimes difficult to extract mRNA directly from patient specimens. METHODS: In this study, we conducted in vitro splicing analysis using a hybrid minigene assay and specimens from three XLAS patients with synonymous variants causing aberrant splicing, including previously reported pathogenic mutations in the same codon. The variants were c.876 A>T (p.Gly292=), c.2358 A>G (p.Pro786=), and c.3906 A>G (p.Gln1302=). RESULTS: The results from our hybrid minigene assay were sufficient to predict splicing abnormalities; c.876 A>T cause 17-bp del and 35-bp del, c.2358 A>G cause exon 29 skipping, c.3906 A>G cause exon 42 skipping, which are very likely to cause pathogenicity. Further, patients carrying c.2358 A>G exhibited a mild phenotype that may have been associated with the presence of both normal and abnormally spliced transcripts. CONCLUSION: The minigene system was shown to be a sensitive assay and a useful tool for investigating the pathogenicity of synonymous variants.Aug. 2020, Molecular genetics & genomic medicine, 8(8) (8), e1342, English, International magazine[Refereed]Scientific journal
- PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.Last, Aug. 2020, Seizure, 80, 12 - 17, English, International magazine[Refereed]Scientific journal
- Early kidney failure in the hereditary type IV collagen disease, Alport syndrome, can be delayed by renin-angiotensin inhibitors. However, whether all patients and all different genotypes respond equally well to this kidney-protective therapy remains unclear. Here, we performed a retrospective study on 430 patients with male X-linked Alport syndrome to examine the relationships among kidney prognosis, genotype, and treatment effect in a large cohort of Japanese patients. We analyzed the clinical features, genotype-phenotype correlation, and kidney survival period for patients treated with or without renin-angiotensin inhibitors. As a result, the median kidney survival period of patients in this cohort was found to be at 35 years with a strong genotype-phenotype correlation. The median age at the onset of end stage kidney disease (ESKD) significantly differed between patients treated with and without renin-angiotensin inhibitors (over 50 years versus 28 years, respectively). Moreover, these drugs delayed the onset of ESKD in patients with truncating variants for 12 years, extending the median age from 16 years to 28 years. Thus, our results confirmed a strong genotype-phenotype correlation in patients with male X-linked Alport syndrome. Additionally, it was suggested that renin-angiotensin inhibitors could significantly delay ESKD progression. Despite these therapies, patients with truncating variants developed ESKD at the median age of 28 years.Jul. 2020, Kidney international, 98(6) (6), 1605 - 1614, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Fukuyama congenital muscular dystrophy (FCMD), which is characterized by generalized muscle weakness, hypotonia, and motor delay during early infancy, gradually progresses with advanced age. Although acute rhabdomyolysis following infection in patients with FCMD has occasionally been reported, no studies have investigated rhabdomyolysis following viral infection in FCMD patients during early infancy. CASE REPORT: We report the case of a 50-day-old girl with no apparent symptoms of muscular dystrophy who developed severe acute rhabdomyolysis caused by viral infection, resulting in quadriplegia and respiratory failure therefore requiring mechanical ventilation. Brain magnetic resonance imaging incidentally showed the typical characteristics of FCMD, and FCMD was confirmed by genetic analysis, which revealed a 3-kb retrotransposon insertion in one allele of the fukutin gene and a deep intronic splicing variant in intron 5 in another allele. The virus etiology was confirmed to be Coxsackie A4. CONCLUSION: We report a severe case of acute rhabdomyolysis with the earliest onset of symptoms due to the Coxsackie A4 virus in a patient with FCMD. The present findings indicate that physicians should consider FCMD with viral infection a differential diagnosis if the patient presents with acute rhabdomyolysis following a fever.May 2020, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26(5) (5), 516 - 519, English, International magazine[Refereed]
- OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome characterized by biphasic seizures with impaired consciousness. AESD is rare outside Asia, and consecutive cohort studies are therefore scarce. Herein, we aimed to describe the detailed characteristics of AESD, including clinical course, electroencephalogram data, laboratory data, imaging findings, treatment, and outcomes. METHODS: We reviewed the clinical database and medical charts of 43 consecutive pediatric patients (<18 years old) who developed AESD between October 1, 2002, and September 30, 2019. RESULTS: We found that AESD occurred even though patients did not develop prolonged seizures. A comparison between the two groups (first seizure duration <30 min and first seizure duration ≥30 min) revealed three main findings: first, patients with AESD who had shorter seizures had better prognosis than those with prolonged seizures; second, patients with AESD who had shorter seizures tended to have earlier occurrence of a second seizure; and third, high signal intensity on diffusion-weighted magnetic resonance imaging was observed mainly in frontal areas, not diffusely, in patients with shorter seizures, and in a broader area in patients with prolonged seizures. CONCLUSIONS: Our description of the detailed clinical picture of AESD may add new insight into its pathophysiology.Last, Apr. 2020, Journal of the neurological sciences, 411, 116684 - 116684, English, International magazine[Refereed]Scientific journal
- Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin β2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin β2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.Apr. 2020, Journal of human genetics, 65(4) (4), 355 - 362, English, International magazine[Refereed]Scientific journal
- (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 271 - 271, JapaneseNICU退院児における感覚特性,発達障害特性の検討
- (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 447 - 447, Japanese当院で出産した精神疾患合併妊婦の特徴および年次推移に関する後方視的検討
- Numerous disease-causing gene mutations have been identified in proteinuric diseases, such as nephrotic syndrome and glomerulosclerosis. This report describes the results of comprehensive genetic diagnosis of Japanese patients with severe proteinuria. In addition, the report describes the clinical characteristics of patients with monogenic disease-causing mutations. We conducted comprehensive gene screening of patients who had either congenital nephrotic syndrome, infantile nephrotic syndrome, steroid-resistant nephrotic syndrome, or focal segmental glomerular sclerosis. Using targeted next-generation sequencing, 60 podocyte-related genes were screened in 230 unrelated patients with proteinuria. A retrospective review of clinical data was conducted for these patients. We detected monogenic disease-causing mutations in 30% (69 of 230) of patients among 19 of the screened genes. Common genes with disease-causing mutations were WT1 (25%), NPHS1 (12%), INF2 (12%), TRPC6 (10%), and LAMB2 (9%). With various immunosuppressive or renoprotective therapies, remission of proteinuria in patients with unknown causative mutations was observed in 26% of patients, whereas only 5% of patients with monogenic disease-causing mutations exhibited complete remission. We assessed the genetic backgrounds of Japanese patients with severe proteinuria. The proportion of patients with gene defects was similar to that of other reports, but the disease-causing gene mutation frequency was considerably different.Jan. 2020, Scientific reports, 10(1) (1), 270 - 270, English, International magazine[Refereed]Scientific journal
- Fibrocartilaginous embolism is assumed to be caused by fibrocartilaginous nucleus pulposus component migration through retrograde embolization to the spinal cord artery. Fibrocartilaginous embolism is currently not well recognized among pediatricians because of its rarity. We describe a previously healthy 15-year-old soccer player who, after kicking a ball, developed progressive weakness in both legs and urinary retention the next day. Magnetic resonance imaging revealed T2 hyperintensity in the anterior horn of the spinal cord at the Th12/L1 level with Schmorl node at the level of L1/2. We also review the previous literature on fibrocartilaginous embolism of the spinal cord in children (less than18 years age); a total of 25 pediatric patients, including our patient, were identified. The median age was 14 years, and 64% of the reviewed patients were female. The most common trigger event was intense exercise or sports. The neurological symptoms started within one day in most cases, and the time to symptom peak varied from a few hours to two weeks. The most common initial neurological symptoms were weakness or plegia (100%), followed by paresthesia or numbness (48%). Affected areas of the spinal cord were distributed evenly from the cervical to thoracolumbar regions. Although steroids and anticoagulants were most commonly used, the prognosis was quite poor (mild to severe sequelae with three deaths). Although fibrocartilaginous embolism is a very rare condition, physicians should be aware of the characteristics and include fibrocartilaginous embolism of the spinal cord in their differential diagnosis, especially for physically active patients.Oct. 2019, Pediatric neurology, 99, 3 - 6, English, International magazine[Refereed]Scientific journal
- X-linked Alport syndrome (XLAS) is a congenital renal disease caused by mutations in COL4A5. In XLAS cases suspected of being caused by aberrant splicing, transcript analysis needs to be conducted to determine splicing patterns and assess the pathogenicity. However, such analysis is not always available. We conducted a functional splicing assay using a hybrid minigene for seven COL4A5 intronic mutations: one was identified by us and six were found in the Human Gene Mutation Database. The minigene assay revealed exon skipping in four variants, exon skipping and a 10-bp insertion in one variant, and no change in one variant, which appeared not to be pathogenic. For one variant, our assay did not work. The results of all three cases for which transcript data were available were consistent with our assay results. Our findings may help to increase the accuracy of genetic test results and clarify the mechanisms causing aberrant splicing.Sep. 2019, Scientific reports, 9(1) (1), 12696 - 12696, English, International magazine[Refereed]Scientific journal
- OBJECTIVE: Although the mortality among previously healthy children with acute encephalopathy (AE) is approximately 5%, their detailed clinical course has not been clarified. The objective of the present study was to describe the detailed clinical course, in minutes, of fatal AE. METHODS: We retrospectively reviewed the medical records of five patients (from 6 months to 14 years of age) who previously had no neurological disorders and were diagnosed with brain death due to AE between 2002 and 2018 at Kobe Children's Hospital. RESULTS: The initial clinical symptoms were convulsion in three cases and impaired consciousness in two. The earliest noted brain imaging abnormality was 7.5 h after neurological symptom detection. Liver enzymes and creatinine levels increased at initial examination, and sodium elevated gradually. All patients met the criteria of systemic inflammatory response syndrome, disseminated intravascular coagulation, and shock within 14 h of symptom detection. High dose steroids and targeted temperature management were initiated 3.5-14 h after onset. Despite these therapies, patients were diagnosed with brain death from 16 h to 4 days after initial neurological symptoms. AE diagnoses were made between 4 h 29 min and 4 days after initial neurological symptoms and included hemorrhagic shock and encephalopathy syndromes, Reye-like syndrome, and acute necrotizing encephalopathy in two, two, and one patient(s), respectively. CONCLUSIONS: We revealed the time series' of clinical events (e.g. SIRS, shock, DIC, AE diagnosis, brain death, and treatments) and laboratory findings relative to initial neurological symptom in fatal AE.Sep. 2019, Brain & development, 41(8) (8), 691 - 698, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3-5 genes. Recently, comprehensive genetic analysis has become the first-line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and comprehensive screening have been published. METHODS: In this study, 441 patients clinically suspected of having AS were divided into two groups and compared. The initial mutational analysis method involved targeted exome sequencing using next-generation sequencing (NGS) (n = 147, NGS group) or Sanger sequencing for COL4A3/COL4A4/COL4A5 (n = 294, Sanger group). RESULTS: In the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes, NPHS1 and EYA1. Further, 239 patients (81%) were diagnosed with AS by initial analysis in the Sanger group. Thirteen patients who were negative for mutation detection in the Sanger group were analyzed by NGS; three were diagnosed with AS. Two had mutations in CLCN5 or LAMB2. The final variant detection rate was 90%. DISCUSSION: Our results reveal that Sanger sequencing and targeted exome sequencing have high diagnostic ability. NGS also has the advantage of detecting other inherited kidney diseases and pathogenic mutations missed by Sanger sequencing.Sep. 2019, Molecular genetics & genomic medicine, 7(9) (9), e883, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a T-cell-mediated autoimmune disorder characterized by bilateral granulomatous panuveitis with various systemic manifestations. Although VKH disease rarely occurs in the pediatric population, the clinical course tends to be aggressive, and the visual prognosis is worse than that in adult patients due to severe ocular complications secondary to recurrent inflammation. CASE PRESENTATION: A 3-year-old girl with probable VKH was referred to Kobe University Hospital. She had severe bilateral panuveitis with posterior synechiae of the iris, marked optic disk swelling, and serous retinal detachment in both eyes, and her best corrected visual acuities (BCVAs) were 20/200 OD and 20/125 OS. A third course of therapy was administered because serous retinal detachment remained after two courses of therapy. She was treated with three courses of high-dose intravenous corticosteroid therapy, followed by slow tapering of oral corticosteroids. Her BCVAs recovered to 20/16 OU, and relapse of ocular inflammation and side effect of treatment were not observed during the 1.5-year follow-up period. CONCLUSIONS: We experienced a pediatric patient with probable VKH disease who was treated with three courses of high-dose intravenous corticosteroid therapy. With the favorable clinical course in our patient, initial treatment with repeated high-dose intravenous corticosteroid therapy might be beneficial in pediatric VKH disease.Aug. 2019, BMC ophthalmology, 19(1) (1), 179 - 179, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Seizures and/or impaired consciousness accompanied by fever without known etiology (SICF) is common in the pediatric emergency setting. No optimal strategy for the management of SICF in childhood currently exists. We previously demonstrated the effectiveness of targeted temperature management (TTM) against SICF with a high risk of morbidity; however, some patients with SICF develop neurological sequelae despite TTM, which necessitate additional neuroprotective treatment. The clinical characteristics of these severe cases have not been studied. Accordingly, the aim of this study was to identify the clinical characteristics of children with SICF who exhibit poor outcomes after TTM. METHODS: The medical records of children admitted to Kobe Children's Hospital (Kobe, Japan) between October 2002 and September 2016 were retrospectively reviewed. Patients with SICF treated using TTM were included and divided into the satisfactory and poor outcome groups. Univariate and multivariate logistic regression analyses were used to compare clinical characteristics and laboratory findings between the two groups. RESULTS: Of the 73 included children, 10 exhibited poor outcomes. Univariate logistic regression analysis revealed that acute circulatory failure before TTM initiation, the use of four or more types of anticonvulsants, methylprednisolone pulse therapy, and an aspartate aminotransferase (AST) level ≥73 IU/L were associated with poor outcomes. Multivariate logistic regression analysis identified an elevated AST level as a significant independent predictor of a poor outcome. CONCLUSIONS: An elevated AST level within 12 h of onset in children with SICF is an independent predictor of a poor outcome after TTM initiated within 24 h of onset.Aug. 2019, Brain & development, 41(7) (7), 604 - 613, English, International magazine[Refereed]Scientific journal
- Advances in molecular genetics have revealed that approximately 30% of cases with steroid-resistant nephrotic syndrome (SRNS) are caused by single-gene mutations. More than 50 genes are responsible for SRNS. One such gene is the nucleoporin, 93-KD (NUP93). Thus far, few studies have reported mutations of NUP93 in SRNS. Here, we describe an NUP93 biallelic mutation in a 9-year-old boy with focal segmental glomerular sclerosis (FSGS). Notably, one mutation comprised an intronic variant; we conducted in vivo and in vitro analysis to characterize this variant. We found two heterozygous mutations in NUP93: c.2137-18G>A in intron 19 and a novel nonsense mutation c.727A>T (p.Lys243*) in exon 8. We conducted RNA sequencing and in vitro splicing assays by using minigene construction, combined with protein expression analysis to determine the pathogenicity of the intronic variant. Both RNA sequencing and in vitro splicing assay showed exon 20-skipping by the intronic variant. In protein expression analysis, aberrant subcellular localization with small punctate vesicles in the cytoplasm was observed for the intronic variant. Taken together, we concluded that c.2137-18G>A was linked to pathogenicity due to aberrant splicing. NUP93 variants are quite rare; however, we have shown that even intronic variants in NUP93 can cause SRNS. This study provides a fundamental approach to validate the intronic variant, as well as new insights regarding the clinical spectrum of SRNS caused by rare gene variants.Jul. 2019, Journal of human genetics, 64(7) (7), 673 - 679, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is necessary for noninvasive management of respiratory clearance in patients with neuromuscular disorders (NMDs). Its utility has been proven, and the technique is recommended in a number of international guidelines for the management of patients with NMDs. However, the clearance of thick secretions adhering to the tracheobronchial walls could be problematic when these patients suffer from respiratory tract infections. To improve the effectiveness of the noninvasive technique, a novel device combining MI-E with high frequency oscillation (HFO) has been developed. However, the efficacy of HFO therapy in NMDs has not been well studied. OBJECTIVE: The aim of this study was to elucidate the effect of MI-E combined with HFO for mucus removal in NMD patients. To evaluate its efficacy, changes in transcutaneous oxygen saturation (SpO2), which may predict intratracheal mucus removal, will be measured before and after use of MI-E. METHODS: This is a single-center, nonblinded, nonrandomized prospective study that will enroll 5 subjects hospitalized in Kobe University Hospital owing to respiratory tract infection. All subjects will receive MI-E therapy a few times daily and will receive HFO every other day, for 6 days. Before and after MI-E use, SpO2 will be obtained and the change in SpO2 (ΔSpO2) between MI-E with and without HFO will be calculated. For every subject, the average of ΔSpO2 with or without HFO will be obtained and the null hypothesis that there is a mean change of 0 in the SpO2 between MI-E with and without HFO will be tested using the paired t test. If the treatment with HFO is found to be statistically significantly superior to the treatment without HFO, the study will conclude that HFO addition is more efficacious than no HFO addition. RESULTS: A total of 2 subjects have already been recruited and enrolled in this study as of August 2018. CONCLUSIONS: This unique protocol will assess the efficacy of adding HFO to MI-E during the acute phase of respiratory tract infection in patients with NMDs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12102.Jun. 2019, JMIR research protocols, 8(6) (6), e12102, English, International magazine[Refereed]Scientific journal
- The detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5 ± 3.3 years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1 ± 3.7 days, 6.0 ± 4.5 days, and 26 ± 34 days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1 ± 4.0 days from onset. The condition of 15 patients (65%) improved within 3 days of high-dose mPSL initiation, whereas, that of four patients began to improve after >5 days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1 week leading to full recovery within 1 month.Jun. 2019, Brain & development, 41(6) (6), 531 - 537, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Recently, comprehensive genetic approaches for steroid-resistant nephrotic syndrome (SRNS) using next-generation sequencing (NGS) have been established, but causative gene mutations could not be detected in almost 70% of SRNS patients. Main reason for the low variant detection rate is that most of them are SRNS caused not by genetic but by immunological factors. But some of them are probably because of the difficulty of detecting copy number variations (CNVs) in causative genes by NGS. METHODS: In this study, we performed two analytical methods of NGS data-dependent pair analysis and custom array comparative genomic hybridization (aCGH) in addition to NGS analysis in an infantile nephrotic syndrome case. RESULTS: We detected only one known pathogenic heterozygous missense mutation in exon 7 of COQ6 c.782C > T, p.(Pro261Leu) by NGS. With pair analysis, heterozygous exon 1-2 deletion was suspected and was confirmed by custom aCGH. As a result, a small CNV was successfully detected in the COQ6 gene. Because we could detect variants in COQ6 and could start treatment by coenzyme Q10 (CoQ10) in his very early stage of SRNS, the patient achieved complete remission. CONCLUSIONS: These relatively novel methods should be adopted in cases with negative results in gene tests by NGS analysis. Especially, in cases with CoQ10 deficiency, it is possible to delay initiating dialysis by starting treatment at their early stages.May 2019, Clinical and experimental nephrology, 23(5) (5), 669 - 675, English, Domestic magazine[Refereed]Scientific journal
- OBJECTIVES: To evaluate the proportion of children presenting to the emergency department (ED) with altered mental status who demonstrate nonconvulsive seizures on reduced-lead electroencephalography (EEG), and to further investigate the characteristics, treatment, and outcomes in these patients compared with patients without nonconvulsive seizures. STUDY DESIGN: In this retrospective cohort study, we reviewed the database and medical records of pediatric patients (aged <18 years) in a single ED between May 1, 2016, and April 30, 2018. We first determined the proportion of nonconvulsive seizures among patients with altered mental status (Glasgow Coma Scale <15). We then compared the clinical presentation, demographic data, clinical diagnosis, EEG results, treatment, and outcomes of patients with altered mental status with nonconvulsive seizures and those without nonconvulsive seizures. RESULTS: In total, 16.9% of the patients with altered mental status (41 of 242; 95% CI, 12.2%-21.6%) evaluated by EEG had detectable nonconvulsive seizure, equivalent to 4.4% (41 of 932) of all patients with altered mental status presenting at our hospital. More than 80% of patients monitored for nonconvulsive seizures had a previous history of seizures, often febrile. Patients with nonconvulsive seizures were older (median, 68.5 vs 36.1 months) and had a higher Pediatric Cerebral Performance Category score at presentation (median, 2.0 vs 1.0). In addition, the proportion of patients admitted to the intensive care unit was significantly higher in the patients with nonconvulsive seizures (30.3% vs 15.0%). However, total duration of hospitalization, neurologic sequelae, and 30-day mortality rate did not differ between the 2 groups. CONCLUSIONS: A relatively high percentage of pediatric patients with altered mental status in the ED experience nonconvulsive seizures. The use of reduced-lead EEG monitoring in the ED might facilitate the recognition and treatment of nonconvulsive seizures, especially among patients with a history of seizures.Apr. 2019, The Journal of pediatrics, 207, 213 - 219, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and impaired consciousness. Takotsubo cardiomyopathy (TTC), which is typically triggered by psychological or physical stress, is characterized by transient myocardial dysfunction affecting the left ventricular apex. Recent reports have suggested that seizures can also trigger TTC. However, no cases of TTC accompanied by AESD have been reported. PATIENT: A previously healthy 4-year-old girl was brought to a hospital with first-time febrile generalized tonic-clonic convulsions, which lasted approximately 40 min. After the seizure resolved, she was intubated due to respiratory deterioration. On the next day, her cardiac function deteriorated, and echocardiography revealed systolic apical ballooning of the left ventricle accompanied by hyperkinesis of the basal wall, which are typical in patients with TTC. Her condition gradually improved, and catecholamine support was tapered. However, 6 days after admission, she experienced a cluster of brief convulsions. Ten days after admission, head MRI revealed lesions with reduced diffusion throughout the cortex, except in the occipital lobe, as well as perirolandic sparing. Follow-up MRI 35 days after onset revealed whole-brain atrophy, following which she developed severe cognitive dysfunction. CONCLUSIONS: Our patient developed TTC accompanied by features of AESD. Our findings may thus provide insight into the development of TTC and prompt further studies regarding the relationship between prolonged seizures and TTC.Mar. 2019, Brain & development, 41(3) (3), 305 - 309, English, International magazine[Refereed]Scientific journal
- Mesenchymal stem cells (MSCs) have considerable therapeutic potential and attract increasing interest in the biomedical field. MSCs are originally isolated and characterized from bone marrow (BM), then acquired from tissues including adipose tissue, synovium, skin, dental pulp, and fetal appendages such as placenta, umbilical cord blood (UCB), and umbilical cord (UC). MSCs are a heterogeneous cell population with the capacity for (1) adherence to plastic in standard culture conditions, (2) surface marker expression of CD73+/CD90+/CD105+/CD45-/CD34-/CD14-/CD19-/HLA-DR- phenotypes, and (3) trilineage differentiation into adipocytes, osteocytes, and chondrocytes, as currently defined by the International Society for Cellular Therapy (ISCT). Although BM is the most widely used source of MSCs, the invasive nature of BM aspiration ethically limits its accessibility. Proliferation and differentiation capacity of MSCs obtained from BM generally decline with the age of the donor. In contrast, fetal MSCs obtained from UC have advantages such as vigorous proliferation and differentiation capacity. There is no ethical concern for UC sampling, as it is typically regarded as medical waste. Human UC starts to develop with continuing growth of the amniotic cavity at 4-8 weeks of gestation and keeps growing until reaching 50-60 cm in length, and it can be isolated during the whole newborn delivery period. To gain insight into the pathophysiology of intractable diseases, we have used UC-derived MSCs (UC-MSCs) from infants delivered at various gestational ages. In this protocol, we describe the isolation and characterization of UC-MSCs from fetuses/infants at 19-40 weeks of gestation.Jan. 2019, Journal of visualized experiments : JoVE, (143) (143), English, International magazine[Refereed]Scientific journal
- Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.Jan. 2019, Epilepsy & behavior : E&B, 90, 15 - 19, English, International magazine[Refereed]Scientific journal
- Introduction: Gitelman syndrome (GS) is a tubulopathy exhibited by salt loss. GS cases are most often diagnosed by chance blood test. Aside from that, some cases are also diagnosed from tetanic symptoms associated with hypokalemia and/or hypomagnesemia or short stature. As for complications, thyroid dysfunction and short stature are known, but the incidence rates for these complications have not yet been elucidated. In addition, no genotype-phenotype correlation has been identified in GS. Methods: We examined the clinical characteristics and genotype-phenotype correlation in genetically proven GS cases with homozygous or compound heterozygous variants in SLC12A3 (n = 185). Results: In our cohort, diagnostic opportunities were by chance blood tests (54.7%), tetany (32.6%), or short stature (7.2%). Regarding complications, 16.3% had short stature, 13.7% had experienced febrile convulsion, 4.3% had thyroid dysfunction, and 2.5% were diagnosed with epilepsy. In one case, QT prolongation was detected. Among 29 cases with short stature, 10 were diagnosed with growth hormone (GH) deficiency and GH replacement therapy started. Interestingly, there was a strong correlation in serum magnesium levels between cases with p.Arg642Cys and/or p.Leu858His and cases without these variants, which are mutational hotspots in the Japanese population (1.76 mg/dl vs. 1.43 mg/dl, P < 0.001). Conclusion: This study has revealed, for the first time, clinical characteristics in genetically proven GS cases in the Japanese population, including prevalence of complications. Patients with hypokalemia detected by chance blood test should have gene tests performed. Patients with GS need attention for developing extrarenal complications, such as short stature, febrile convulsion, thyroid dysfunction, epilepsy, or QT prolongation. It was also revealed for the first time that hypomagnesemia was not severe in some variants in SLC12A3.Jan. 2019, Kidney international reports, 4(1) (1), 119 - 125, English, International magazine[Refereed]Scientific journal
- CD80, which regulates T cell activation, may provide a differential diagnostic marker between minimal change disease (MCD) and other renal diseases, including focal segmental glomerular sclerosis (FSGS). However, recent reports show contrasting results. Therefore, we evaluated the utility of urinary CD80 as a diagnostic biomarker. We collected 65 urine samples from 55 patients with MCD (n = 31), FSGS (n = 4), inherited nephrotic syndrome (n = 4), Alport syndrome (n = 5) and other glomerular diseases (n = 11), and control samples (n = 30). We measured urinary CD80 levels by ELISA. Urinary CD80 (ng/gCr) (median, interquartile range) levels were significantly higher in patients with MCD in relapse (91.5, 31.1-356.0), FSGS (376.2, 62.7-1916.0), and inherited nephrotic syndrome (220.1, 62.9-865.3), than in patients with MCD in remission (29.5, 21.7-52.8) (p < 0.05). Elevation of urinary CD80 was observed, even in patients with inherited nephrotic syndrome unrelated to T cell activation. Additionally, urinary CD80 was positively correlated with urinary protein levels. Our results suggest that urinary CD80 is unreliable as a differential diagnostic marker between MCD in relapse and FSGS or inherited kidney diseases. Increased urinary CD80 excretion was present in all patients with active kidney disease.Nov. 2018, Scientific reports, 8(1) (1), 17322 - 17322, English, International magazine[Refereed]Scientific journal
- Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass, and some patients show deterioration of clinical condition with neurological symptoms. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome that is characterized by biphasic seizures and impaired consciousness with reduced diffusion in the subcortical white matter on magnetic resonance imaging, typically observed between days 3 and 9 after clinical onset. Although AFBN sometimes causes neurological symptoms, no cases of AFBN with AESD have been reported, and no studies have presented the cytokine profiles of patients with a severe form of acute encephalopathy with AFBN. We report here a very rare case involving a 6-month-old boy who developed AFBN due to Enterococcus faecalis with both the clinical and radiological features of AESD. In our patient, serum interleukin (IL)-6, IL-10, and interferon (IFN)-γ levels markedly increased on admission, and on day 4, only IL-6 levels significantly increased in the cerebrospinal fluid (CSF). These results suggest that high serum cytokines are produced locally in response to AFBN and elevated IL-6 levels in CSF may have neuroprotective roles.Nov. 2018, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 24(11) (11), 932 - 935, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Fosphenytoin (fPHT) and continuous intravenous midazolam (cMDL) had commonly been used as second-line treatments for pediatric status epilepticus (SE) in Japan. However, there is no comparative study of these two treatments. METHODS: We included consecutive children who 1) were admitted to Kobe Children's Hospital because of convulsion with fever and 2) were treated with either fPHT or cMDL as second-line treatment for convulsive SE lasting for longer than 30 min. We compared, between the fPHT and cMDL groups, the proportion of barbiturate coma therapy (BCT), incomplete recovery of consciousness, mechanical ventilation, and inotropic agents. RESULTS: The proportion of BCT was not significantly different between the two groups (48.7% [20/41] in fPHT and 35.3% [29/82] in cMDL, p = 0.17). The prevalence of incomplete recovery of consciousness, mechanical ventilation, and inotropic agents was not different between the two groups. After excluding 49 patients treated with BCT, incomplete recovery of consciousness 6 h and 12 h after onset was more frequent in the cMDL group than in the fPHT group (71.7% vs. 33.3%, p < 0.01; 56.6% vs. 14.2%, p < 0.01; respectively). Mechanical ventilation was more frequent in the cMDL group than in the fPHT group (32.0% vs. 4.7%, p = 0.01). CONCLUSIONS: Our results suggest that 1) the efficacy of fPHT and cMDL is similar, although cMDL may prevent the need for BCT compared with fPHT, and 2) fPHT is relatively safe as a second-line treatment for pediatric SE in patients who do not require BCT.Nov. 2018, Brain & development, 40(10) (10), 884 - 890, English, International magazine[Refereed]Scientific journal
- By whole exome sequencing, we identified three de novo RHOBTB2 variants in three patients with epileptic encephalopathies (EEs). Interestingly, all three patients showed acute encephalopathy (febrile status epilepticus), with magnetic resonance imaging revealing hemisphere swelling or reduced diffusion in various brain regions. RHOBTB2 encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor or itself is a substrate for the Cullin-3 (CUL3)-based ubiquitin ligase complex. Transient expression experiments in Neuro-2a cells revealed that mutant RHOBTB2 was more abundant than wild-type RHOBTB2. Coexpression of CUL3 with RHOBTB2 decreased the level of wild-type RHOBTB2 but not the level of any of the three mutants, indicating impaired CUL3 complex-dependent degradation of the three mutants. These data indicate that RHOBTB2 variants are a rare genetic cause of EEs, in which acute encephalopathy might be a characteristic feature, and that precise regulation of RHOBTB2 levels is essential for normal brain function.Aug. 2018, Human mutation, 39(8) (8), 1070 - 1075, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Children who present with seizure and/or impaired consciousness accompanied by fever without known etiology (SICF) may be diagnosed with either acute encephalopathy (AE) or febrile seizure (FS). Although approximately 5% of AE cases are fatal, it is difficult to identify fatal cases among children with SICF, which are often critical by the time of diagnosis. Thus, early prediction of outcomes for children with SICF, prior to diagnosis, may help to reduce mortality associated with AE. The aim of the present study was to identify clinical and laboratory risk factors for mortality acquired within 6 h of onset among children with SICF. METHODS: We retrospectively reviewed the medical records of children who had been admitted to Kobe Children's Hospital (Kobe, Japan) with SICF between October 2002 and September 2015. We compared clinical and laboratory characteristics acquired within 6 h of onset and outcomes between survivors and non-survivors using univariate and multivariate analyses. RESULTS: The survivor and non-survivor groups included 659 and nine patients, respectively. All patients in the non-survivor group received a final diagnosis of AE. Univariate analysis revealed significant differences between the groups with regard to seizure duration and the following laboratory parameters: aspartate transaminase (AST), alanine aminotransferase, lactate dehydrogenase, sodium, and lactate. The multivariate analysis identified AST as a significant independent factor associated with mortality. CONCLUSIONS: Elevation of AST within 6 h of onset is independently correlated with mortality in children with SICF. Our result may elucidate earlier intervention for patients with high risk of mortality.Aug. 2018, Brain & development, 40(7) (7), 552 - 557, English, International magazine[Refereed]Scientific journal
- Pseudo-Bartter/Gitelman syndrome (p-BS/GS) encompasses a clinically heterogeneous group of inherited or acquired disorders similar to Bartter syndrome (BS) or Gitelman syndrome (GS), both renal salt-losing tubulopathies. Phenotypic overlap frequently occurs between p-BS/GS and BS/GS, which are difficult to diagnose based on their clinical presentation and require genetic tests for accurate diagnosis. In addition, p-BS/GS can occur as a result of other inherited diseases such as cystic fibrosis, autosomal dominant hypocalcemia, Dent disease, or congenital chloride diarrhea (CCD). However, the detection of the variants in genes other than known BS/GS-causing genes by conventional Sanger sequencing requires substantial time and resources. We studied 27 cases clinically diagnosed with BS/GS, but with negative genetic tests for known BS/GS genes. We conducted targeted sequencing for 22 genes including genes responsible for tubulopathies and other inherited diseases manifesting with p-BS/GS symptoms. We detected the SLC26A3 gene variants responsible for CCD in two patients. In Patient 1, we found the SLC26A3 compound heterozygous variants: c.354delC and c.1008insT. In Patient 2, we identified the compound heterozygous variants: c.877G > A, p.(Glu293Lys), and c.1008insT. Our results suggest that a comprehensive genetic screening system using targeted sequencing is useful for the diagnosis of patients with p-BS/GS with alternative genetic origins.Jul. 2018, Journal of human genetics, 63(8) (8), 887 - 892, English, International magazine[Refereed]Scientific journal
- Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07-41.66) was indicated, too few events (0-2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.May 2018, Journal of autism and developmental disorders, 48(5) (5), 1483 - 1491, English, International magazine[Refereed]Scientific journal
- Objectives To identify clinical features that predict Group A streptococcal (GAS) pharyngitis in a Japanese paediatric primary emergency medical centre. Methods The prevalence of GAS pharyngitis according to age and body temperature (BT) was calculated among 3098 paediatric patients with pharyngitis. The numbers of GAS-positive and -negative patients for each clinical parameter, and each point increase in the McIsaac score were compared and likelihood ratios (LRs) were calculated. Results The prevalence of GAS pharyngitis was extremely low in patients aged < 1 (1.2%) and 1 year (3.9%). The GAS-positive rate was significantly higher in patients with a BT < 38.0°C compared with ≥ 38.0°C (30.0% vs. 19.8%). A BT ≥ 38.0°C was not a predictive finding for GAS pharyngitis (positive LR: 0.82). Rash was the most useful individual predictor, and a McIsaac score of 4 or 5 increased the probability; however, the positive LRs were 1.74 and 1.30, respectively. Conclusions The prevalence of GAS pharyngitis is extremely low in patients aged < 1 and 1 year, and a BT ≥ 38.0°C is not a predictive symptom. Although a rash and McIsaac score of 4 or 5 are associated with an increased probability, they cannot be used to confirm GAS infection.May 2018, The Journal of international medical research, 46(5) (5), 1791 - 1800, English, International magazine[Refereed]Scientific journal
- The pattern of X-chromosome inactivation (XCI) can affect the clinical severity of X-linked disorders in females. XCI pattern analysis has been conducted mainly by HUMARA assay, a polymerase chain reaction-based assay using a methylation-sensitive restriction enzyme. However, this assay examines the XCI ratio of the androgen receptor gene at the genomic DNA level and does not reflect the ratio of either targeted gene directly or at the mRNA level. Here, we report four females with Dent disease, and we clarified the correlation between XCI and female cases of Dent disease using not only HUMARA assay but also a novel analytical method by RNA sequencing. We constructed genetic analysis for 4 female cases showing high level of urinary low-molecular-weight proteinuria and their parents. Their XCI pattern was analyzed by both HUMARA assay and an ultra-deep targeted RNA sequencing of the CLCN5 gene using genomic DNA and mRNA extracted from both leukocytes and urine sediment. All four cases possessed pathogenic variants of the CLCN5 gene. XCI analysis revealed skewed XCI in only two cases, while the other two showed random XCI. All assay results of HUMARA and targeted RNA sequencing in both leukocytes and urinary sediment were clearly identical in all four cases. We developed a novel XCI analytical assay of ultra-deep targeted RNA sequencing and revealed that skewed XCI explains the mechanism of onset of female Dent disease in only half of such cases.May 2018, Journal of human genetics, 63(5) (5), 589 - 595, English, International magazine[Refereed]Scientific journal
- Blackwell Publishing Ltd, Apr. 2018, Clinical Genetics, 93(4) (4), 931 - 933, English[Refereed]Scientific journal
- Several studies describing the diurnal occurrence of febrile seizures have reported greater seizure frequency early or late in the evening relative to midnight or early morning. However, no articles have reported on the diurnal occurrence of complex febrile seizure. Moreover, no studies have addressed the relationship between seizure severity and diurnal occurrence. We retrospectively evaluated complex febrile seizures in 462 children needing hospitalization, and investigated the relationship between severity and diurnal occurrence according to four categorized time periods (morning, afternoon, evening, and night). Our study showed that complex febrile seizures occurred most often in the evening, peaking around 18:00 (18:00-18:59), and least often at night (02:00-02:59). In addition, the frequency with which patients developed status epilepticus or needed anticonvulsant treatments was also lower during the night. However, the seizure duration and the proportion of the patients who needed anticonvulsant treatment were the same among the four time periods. Furthermore, we compared three subclasses (repeated episodes of convulsions, focal seizures, and prolonged seizures (≧15min)), two of the complex features (focal seizures and prolonged seizures), and all complex features among the four time periods. However, they were the same among the four time periods. Taken together, our data indicate that although the severity of seizures was stable over a 24-hour period, the occurrence of seizures in our cohort of pediatric patients with complex febrile seizures requiring hospitalization was highest in the evening and lowest at night.Mar. 2018, Epilepsy & behavior : E&B, 80, 280 - 284, English, International magazine[Refereed]Scientific journal
- (公社)日本小児科学会, Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 313 - 313, English複雑型熱性けいれんの好発時間帯とその重症度(Diurnal Occurrence of Complex Febrile Seizure and its Severity in Children)[Refereed]Scientific journal
- 2018, Brain and Development, 60(8) (8), 648 - 690, EnglishFosphenytoin vs. continuous midazolam for pediatric febrile status epilepticusScientific journal
- Blackwell Publishing, Jan. 2018, Pediatrics International, 60(1) (1), 67 - 69, English[Refereed]Scientific journal
- Recently, haploinsufficiency of PURA has been identified as an essential cause of 5q31.3 microdeletion syndrome, which is characterized by severe psychomotor developmental delay, epilepsy, distinctive features, and delayed myelination. A new 5q31.2-q31.3 microdeletion that included PURA was identified in a patient with infantile spasms. Approximately 50% of patients with PURA-related neurodevelopmental disorders exhibited epilepsy regardless of whether they harbor a 5q31.3 deletion or PURA mutation. Patients with the 5q31.3 deletion or a PURA mutation should be carefully monitored for epileptic seizures.2018, Human genome variation, 5, 18007 - 18007, English, International magazine[Refereed]Scientific journal
- Blackwell Publishing, Jan. 2018, Pediatrics International, 60(1) (1), 67 - 69, English[Refereed]Scientific journal
- Dec. 2017, Environmental Health and Preventive Medicine (Web), 22(1) (1), 22:15 (WEB ONLY), EnglishChanges in the numbers of patients with acute gastroenteritis after voluntary introduction of the rotavirus vaccine in a Japanese children's primary emergency medical center[Refereed]Scientific journal
- Nov. 2017, BMJ Open, 7(11) (11), e016675, English[Refereed]Scientific journal
- BACKGROUND: Non-invasive transcutaneous bilirubin (TcB) monitoring has been widely used to screen for hyperbilirubinemia. TcB measured using the recently developed BiliCare™ system, however, has not been fully evaluated. METHODS: One hundred and seven TcB measurements were obtained from 82 Japanese newborns ≥35 weeks' gestational age within 2 weeks after birth. Measurements were taken at the scaphoid fossa, conchal cavity, and lobe of the ear using BiliCare. BiliCare TcB were compared with total serum bilirubin (TB) and TcB obtained using another bilirubinometer (JM-105™). RESULTS: Transcutaneous bilirubin measured at all three sites significantly correlated with TB (r = 0.91, 0.93, and 0.93 at the scaphoid fossa, conchal cavity, and lobe, respectively). The mean differences were 0.1, -0.3, and 3.6 at the scaphoid fossa, conchal cavity, and lobe, respectively. BiliCare TcB at the scaphoid fossa significantly correlated with that using the JM-105 (r = 0.91). The mean difference was 0.0. BiliCare, however, produced a significantly higher and lower TcB than the JM-105 for TB <7 and ≥15 mg/dL, respectively. CONCLUSIONS: Transcutaneous bilirubin measurements taken at the scaphoid fossa or conchal cavity using BiliCare were more reliable than those at the earlobe. BiliCare TcB differed from those of the JM-105, for TB <7 or ≥15 mg/dL.Oct. 2017, Pediatrics international : official journal of the Japan Pediatric Society, 59(10) (10), 1058 - 1063, English, International magazine[Refereed]Scientific journal
- Oct. 2017, PEDIATRICS INTERNATIONAL, 59(10) (10), 1058 - 1063, English[Refereed]Scientific journal
- Oct. 2017, BRAIN & DEVELOPMENT, 39(9) (9), 756 - 762, English[Refereed]Scientific journal
- (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S360 - S360, Japanese
- (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S299 - S299, Japanese有熱性けいれん重積症例におけるAESDおよび急性脳症鑑別のためのAESD prediction scoreの有用性の検証[Refereed]
- (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S300 - S300, JapaneseTargeted temperature managementを導入した急性脳症疑い症例における早期予後因子の検討[Refereed]
- (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S301 - S301, Japanese発症6時間以内に得られる急性脳症死亡予測因子の検討[Refereed]
- (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S346 - S346, Japanese小児難治てんかん重積状態に対するチアミラールを用いた全身麻酔療法[Refereed]
- May 2017, BRAIN & DEVELOPMENT, 39(5) (5), 452 - 454, English[Refereed]Scientific journal
- Apr. 2017, Brain & Development, 39(3 Supplement) (3 Supplement), 330, EnglishEfficacy and Complications of Fosphenytoin Versus Continuous Midazolam in Children with Febrile Status Epilepticus[Refereed]Scientific journal
- Apr. 2017, Brain & Development, 39(3 Supplement) (3 Supplement), 124, EnglishDescription of Clinical Course and Predictive Score in Fatal Acute Encephalopathy[Refereed]Scientific journal
- Mar. 2017, JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 39(2) (2), E92 - E96, English[Refereed]
- (公社)日本小児科学会, Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 374 - 374, Japanese超低出生体重児のSGA性低身長症に対する成長ホルモン治療の検討
- 2017, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 22(1) (1), 15, English[Refereed]Scientific journal
- Dec. 2016, SCIENTIFIC REPORTS, 6, 38659, English[Refereed]Scientific journal
- Sep. 2016, BRAIN & DEVELOPMENT, 38(8) (8), 731 - 737, English[Refereed]Scientific journal
- Sep. 2016, JOURNAL OF INFECTION AND CHEMOTHERAPY, 22(9-10) (9-10), 712 - 715, English[Refereed]Scientific journal
- (一社)日本小児神経学会, May 2016, 脳と発達, 48(Suppl.) (Suppl.), S275 - S275, Japanese
- (一社)日本小児神経学会, May 2016, 脳と発達, 48(Suppl.) (Suppl.), S393 - S393, Japanese
- 2016, Case reports in neurological medicine, 2016, 7528238[Refereed]
- Oct. 2015, BRAIN & DEVELOPMENT, 37(9) (9), 911 - 915, English[Refereed]Scientific journal
- Aug. 2015, PEDIATRICS INTERNATIONAL, 57(4) (4), 659 - 664, English[Refereed]Scientific journal
- May 2015, PEDIATRIC NEUROLOGY, 52(5) (5), 499 - 503, English[Refereed]Scientific journal
- Mar. 2015, BRAIN & DEVELOPMENT, 37(3) (3), 328 - 333, English[Refereed]Scientific journal
- Nov. 2014, BRAIN & DEVELOPMENT, 36(10) (10), 928 - 931, English[Refereed]Scientific journal
- Jul. 2014, PEDIATRIC NEUROLOGY, 51(1) (1), 78 - 84, English[Refereed]Scientific journal
- Jun. 2013, PEDIATRICS INTERNATIONAL, 55(3) (3), 310 - 314, English[Refereed]Scientific journal
- Dec. 2012, PEDIATRICS INTERNATIONAL, 54(6) (6), 892 - 898, English[Refereed]Scientific journal
- Nov. 2011, No To Hattatsu, 43(6) (6), 459 - 463, JapaneseInduced hypothermia/normothermia with general anesthesia prevents neurological damage in febrile refractory status epilepticus in children[Refereed]Scientific journal
- Validity of caregivers' reports on head trauma due to falls in young children aged less than 2 years.OBJECTIVE: The clinical presentations of head trauma due to falls among young children aged less than 2 years are controversial, particularly in Japan, as the history of trauma recounted by a caretaker is not always reliable. The purpose of this study was to assess the validity of caregiver's reports on head trauma due to falls in young children aged less than 2 years in Japan. METHODS: All patients <2 years of age presenting with head trauma resulting from a fall who were admitted to 3 children's hospitals in Japan from January 2001 to December 2005 were retrospectively reviewed (N = 58). The clinical presentations were compared among groups categorized by the heights from which the patient fell (short (≤120 cm) or long (>120 cm)) and the surface on which the patient landed (carpet, tatami (Japanese mattress), hardwood floor, or concrete). RESULTS: Patients who suffered short falls were more likely to present with subdural hemorrhage (SDH) than those who suffered long falls (74% and 40%, respectively, P = 0.027). More specifically, 62% of short falls showed SDH indicative of shaken baby syndrome (e.g. multilayer SDH). Neurological symptoms, cyanosis, and SDH were more commonly observed in patients who landed on carpeted or tatami surfaces than in those who landed on hardwood or concrete floors. CONCLUSIONS: Short falls and landing on soft surfaces resulted in the presentation of severer clinical symptoms than did long falls and landing on hard surfaces, suggesting that the validity of caretakers' reports on infant or young children's head trauma due to falls is low. Further research is warranted to investigate the cause of infant head trauma due to falls.2010, Clinical medicine insights. Pediatrics, 4, 11 - 8, English, International magazine[Refereed]Scientific journal
- Jan. 2010, No To Hattatsu, 42(1) (1), 23 - 28, JapaneseContinuous electroencephalogram monitoring in a pediatric intensive care unit[Refereed]Scientific journal
- (一社)日本小児神経学会, May 2009, 脳と発達, 41(Suppl.) (Suppl.), S176 - S176, Japanese小児頭部外傷患者におけるNICE頭部外傷ガイドラインの有用性[Refereed]
- (一社)日本小児神経学会, May 2009, 脳と発達, 41(Suppl.) (Suppl.), S244 - S244, Japanese複雑型熱性痙攣で発症する急性脳炎・脳症の臨床的治療開始基準の提案[Refereed]
- 日本脳低温療法・体温管理学会, Jul. 2008, 日本脳低温療法学会プログラム・抄録集, 11回, 29 - 29, Japanese小児に対する脳低温療法 小児における脳低温療法 小児急性脳炎・脳症に対するデキサメサゾン併用脳低温療法の介入による神経学的予後の比較検討[Refereed]
- (一社)日本小児神経学会, May 2008, 脳と発達, 40(Suppl.) (Suppl.), S261 - S261, Japanese乳幼児の虐待が疑われる外傷性脳傷害患者は外傷ではなく、神経症状を主訴に来院する[Refereed]
- 日本脳低温療法・体温管理学会, Jul. 2007, 日本脳低温療法学会プログラム・抄録集, 10回, 55 - 55, Japanese小児脳低温療法における頭蓋内圧センサー挿入症例の検討[Refereed]
- Jan. 2007, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 352(1) (1), 12 - 16, English[Refereed]Scientific journal
- Mar. 2006, BIOLOGY OF THE CELL, 98(3) (3), 153 - 161, English[Refereed]Scientific journal
- Feb. 2002, PEDIATRICS INTERNATIONAL, 44(1) (1), 60 - 63, EnglishEffects of child seats on the cardiorespiratory function of newborns[Refereed]Scientific journal
- (公社)日本小児科学会, Dec. 1998, 日本小児科学会雑誌, 102(12) (12), 1351 - 1351, Japanese急性骨髄性白血病(AML)の治療中に多発性気管支ポリープを伴うアスペルギルス肺炎を合併した1男児例[Refereed]
- (公社)日本小児科学会, Aug. 2024, 日本小児科学会雑誌, 128(8) (8), 1031 - 1044, Japanese脳保護のための小児神経集中治療
- (一社)日本小児精神神経学会, Jun. 2024, 日本小児精神神経学会プログラム・抄録集, 131回, 52 - 52, Japanese神戸市における発達障害に対する乳幼児二次健診の取り組み
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S112 - S112, Japanese脳保護のための小児神経集中治療 脳保護を指向した小児神経集中治療
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S200 - S200, Japanese
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S206 - S206, Japanese
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S225 - S225, Japanese
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S225 - S225, Japanese
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S229 - S229, Japanese
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S231 - S231, Japanese
- (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S298 - S298, Japanese
- (一社)日本小児精神神経学会, Apr. 2024, 小児の精神と神経, 64(1) (1), 82 - 83, Japanese1歳6ヵ月児の神経学的発達の検討 新型コロナウイルス感染症流行前後での変化
- (公社)日本小児科学会, Apr. 2024, 日本小児科学会雑誌, 128(4) (4), 625 - 625, Japanese3歳時の就寝時刻が遅いと小学1年生時の勤勉性や思いやりが低下する 尼崎市コホート研究
- (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 151 - 151, Japanese
- (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 152 - 152, Japanese
- (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 188 - 188, Japanese3歳児の睡眠習慣と小学1年生の学力および非認知能力との関連
- (公社)日本小児科学会, Feb. 2024, 日本小児科学会雑誌, 128(2) (2), 253 - 253, Japanese前向き多施設レジストリによる急性脳症の病型および治療の実態調査
- (一社)日本小児精神神経学会, Nov. 2023, 日本小児精神神経学会プログラム・抄録集, 130回, 77 - 77, Japanese1歳6ヵ月児の神経学的発達の検討 新型コロナウイルス感染症流行前後での変化
- (一社)日本神経学会, Sep. 2023, 臨床神経学, 63(Suppl.) (Suppl.), S284 - S284, Japanese結節性硬化症における皮質結節の性状とてんかん性放電の関連
- (一社)日本てんかん学会, Sep. 2023, てんかん研究, 41(2) (2), 326 - 326, Japanese意識障害を呈した小児に対する救急外来簡易脳波の原因疾患別特徴
- (一社)日本てんかん学会, Sep. 2023, てんかん研究, 41(2) (2), 349 - 349, JapaneseDravet症候群に合併した急性脳症の4例
- (一社)日本てんかん学会, Sep. 2023, てんかん研究, 41(2) (2), 421 - 421, Japanese有熱性けいれん発作をきたした小児における発症早期の非けいれん性発作
- (一社)日本小児心身医学会, Aug. 2023, 子どもの心とからだ, 32(2) (2), 332 - 332, Japanese食事制限を要する先天性代謝異常症における摂食障害
- (公社)日本小児保健協会, May 2023, 小児保健研究, 82(講演集) (講演集), 138 - 138, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S212 - S212, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S284 - S284, Japanese3歳時の就寝時刻または睡眠時間と小学1年生の学力との関連 尼崎市の人口ベースの研究
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S287 - S287, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S310 - S310, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S315 - S315, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S316 - S316, Japanese
- (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S318 - S318, Japanese
- (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 628 - 628, Japanese当院での脳症関連遺伝子パネルを用いた疾患関連遺伝子の同定の試み
- (一社)西宮市医師会, Mar. 2023, 西宮市医師会医学雑誌, (28) (28), 56 - 56, Japaneseウイルス関連急性脳症 治療から予防へ
- (株)東京医学社, 2023, 小児内科, 55(増刊) (増刊), 508 - 512, JapaneseAcute encephalopathy
- (一社)日本てんかん学会, Aug. 2022, てんかん研究, 40(2) (2), 410 - 410, Japaneseてんかん重積状態・急性脳症における疾患原因遺伝子の同定の試み
- (一社)日本てんかん学会, Aug. 2022, てんかん研究, 40(2) (2), 457 - 457, Japanese発熱を伴う30分以上のけいれん性てんかん重積状態における転帰不良の予測
- (公社)日本小児保健協会, May 2022, 小児保健研究, 81(講演集) (講演集), 152 - 152, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S139 - S139, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S155 - S155, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S223 - S223, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S223 - S223, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S251 - S251, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S252 - S252, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S253 - S253, Japanese
- (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S317 - S317, Japanese
- (公社)日本小児科学会, Feb. 2022, 日本小児科学会雑誌, 126(2) (2), 369 - 369, Japanese幼児期の生活習慣と小学1年生の学力との関連 3歳時点での就寝時刻が遅いと学力が低下する
- (一社)日本小児神経学会, May 2021, 脳と発達, 53(Suppl.) (Suppl.), S174 - S174, Japanese
- (一社)日本小児神経学会, May 2021, 脳と発達, 53(Suppl.) (Suppl.), S267 - S267, Japanese
- (一社)日本小児神経学会, May 2021, 脳と発達, 53(Suppl.) (Suppl.), S268 - S268, Japanese
- (一社)日本小児神経学会, May 2021, 脳と発達, 53(Suppl.) (Suppl.), S268 - S268, Japanese
- (一社)日本小児神経学会, May 2021, 脳と発達, 53(Suppl.) (Suppl.), S274 - S274, Japanese
- (一社)日本てんかん学会, 2021, てんかん研究, 39(2) (2), 316 - 316, JapaneseAutomated seizure detection system using rhythmic wave analysis for children with altered mental state
- 2021, 小児科臨床, 74私の処方2021 V.神経・筋疾患の処方 4.急性脳症の管理
- (公社)日本小児科学会, 2021, 日本小児科学会雑誌, 125(2) (2), 291 - 291, JapaneseA SMA1 infant who received Zolgensma therapy at the age of 50 days
- (一社)日本小児心身医学会, 2021, 子どもの心とからだ, 30(2) (2), 235 - 235, Japanese乳幼児期発症ARFIDに対する行動療法
- (一社)日本医療保育学会, 2021, 医療と保育, 19(1) (1), 24 - 33, JapaneseReparenting therapy with childcare in eating disorders
- (一社)日本臨床神経生理学会, Oct. 2020, 臨床神経生理学, 48(5) (5), 529 - 529, Japanese
- (公社)日本小児科学会, Aug. 2020, 日本小児科学会雑誌, 124(8) (8), 1294 - 1294, Japanese熱性けいれん重積管理の最適化は急性脳症を減らすのか?
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S82 - S82, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S161 - S161, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S232 - S232, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S263 - S263, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S264 - S264, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S265 - S265, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S266 - S266, Japanese
- (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S266 - S266, Japanese
- (一社)日本小児心身医学会, May 2020, 子どもの心とからだ, 29(1) (1), 22 - 26, Japanese
- (株)日本小児医事出版社, Apr. 2020, 小児科臨床, 73(4) (4), 499 - 502, Japanese
- (公社)日本小児科学会, 2020, 日本小児科学会雑誌, 124(2) (2), 398 - 398, Japanese詳細な問診から診断に至った線維軟骨塞栓症の一例
- (公社)日本小児科学会, 2020, 日本小児科学会雑誌, 124(2) (2), 288 - 288, Japanese神戸市における熱性けいれんの発症頻度:後期早産であることのリスクの検討
- 2020, 日本小児科学会雑誌, 124(6) (6)胃腸炎罹患後に低血糖発作をおこした中鎖アシルCoA脱水素酵素(MCAD)欠損症の1例
- 2020, 日本小児科学会雑誌, 124(6) (6)治療抵抗性の眼筋型重症筋無力症に対してステロイドパルス療法を行った2歳女児例
- (一社)日本小児心身医学会, 2020, 子どもの心とからだ, 29(2) (2), 232 - 232, Japanese神経性やせ症の小児科入院中の遊びを中心とした行動と予後の関連
- (一社)日本小児精神神経学会, Oct. 2019, 小児の精神と神経, 59(3) (3), 269 - 270, Japanese修正18〜24ヵ月のNICU退院児における感覚特性の検討
- (一社)日本てんかん学会, Sep. 2019, てんかん研究, 37(2) (2), 377 - 378, Japanese救急・集中治療におけるてんかん重積状態への対応 けいれん性てんかん重積治療における持続脳波モニタリング
- (一社)日本てんかん学会, Sep. 2019, てんかん研究, 37(2) (2), 637 - 637, Japanese新規STXBP1変異を認め大田原症候群と診断したSTXBP1脳症
- (一社)日本てんかん学会, Sep. 2019, てんかん研究, 37(2) (2), 675 - 675, Japanese小児難治てんかん重積状態における急性期の血中サイトカイン推移
- (一社)日本てんかん学会, Sep. 2019, てんかん研究, 37(2) (2), 705 - 705, Japanese在胎週数毎に層別化した熱性けいれんの発生頻度 population-based study
- (一社)日本小児心身医学会, Aug. 2019, 子どもの心とからだ, 28(2) (2), 279 - 279, Japanese摂食障害児に対する保育を取り入れた小児科病棟での入院治療
- (一社)日本小児精神神経学会, Jun. 2019, 日本小児精神神経学会プログラム・抄録集, 121回(3) (3), 43 - 43, Japanese修正18〜24ヵ月のNICU退院児における感覚特性の検討
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S239 - S239, Japanese小児けいれん重積に対する脳波モニタリング下ミダゾラム昏睡療法の有効性と安全性
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S239 - S239, Japanese有熱性難治性けいれん重積の治療プロトコル変遷による短期的予後の検討
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S267 - S267, Japanese出血性ショック脳症症候群(HSES)7症例の詳細な臨床経過の検討
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S267 - S267, Japanese時間単位で評価した急性脳症のサイトカイン動態解析(第1報)
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S268 - S268, Japanese時間単位で評価した急性脳症のサイトカイン動態解析(第2報)
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S288 - S288, Japanese1歳以降にヌシネルセン治療を開始した脊髄性筋萎縮症1型の3例
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S239 - S239, Japanese小児けいれん重積に対する脳波モニタリング下ミダゾラム昏睡療法の有効性と安全性
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S239 - S239, Japanese有熱性難治性けいれん重積の治療プロトコル変遷による短期的予後の検討
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S267 - S267, Japanese出血性ショック脳症症候群(HSES)7症例の詳細な臨床経過の検討
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S267 - S267, Japanese時間単位で評価した急性脳症のサイトカイン動態解析(第1報)
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S268 - S268, Japanese時間単位で評価した急性脳症のサイトカイン動態解析(第2報)
- (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S288 - S288, Japanese1歳以降にヌシネルセン治療を開始した脊髄性筋萎縮症1型の3例
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 615 - 615, Japanese酵素活性・負荷試験で異常を認めなかった糖原病IXa型の2歳男児例
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 616 - 616, Japanese1型糖尿病患者に対するグルカゴンの処方実態
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 620 - 620, Japanese急性散在性脳脊髄炎の髄液所見の検討
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 623 - 623, Japanese新生児マススクリーニングを契機に発見された先天性乳糖不耐症の新生児例
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 629 - 629, Japanese結節性硬化症の定期検査により早期発見に至った無症候性巨細胞性星細胞腫瘍(SEGA)の1例
- (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 630 - 630, Japaneseバセドウ病を合併した若年ミオクロニーてんかんの1例
- (公社)日本小児科学会, Feb. 2019, 日本小児科学会雑誌, 123(2) (2), 366 - 366, Japanese幼児期からヌシネルセン治療を開始した脊髄性筋萎縮症3型の2例の経過
- (一社)日本小児精神神経学会, Oct. 2018, 小児の精神と神経, 58(3) (3), 201 - 207, JapaneseCharacterization of Sensory Processing Function in Infants/Toddlers with Developmental Disorder
- 12 Sep. 2018, てんかん研究, 36(2) (2), 324, Japanese三次診療施設における小児のけいれん重積治療と予後
- (一社)日本てんかん学会, 12 Sep. 2018, てんかん研究, 36(2) (2), 408 - 408, Japanese一過性意識消失発作を主訴に小児神経外来を受診した101例の最終診断
- (一社)日本てんかん学会, 12 Sep. 2018, てんかん研究, 36(2) (2), 482 - 482, Japanese有熱性けいれん重積状態の小児における非けいれん性発作
- (一社)日本てんかん学会, 12 Sep. 2018, てんかん研究, 36(2) (2), 464 - 464, Japanese小児におけるカルバマゼピンとレベチラセタムによる血清脂質値および甲状腺ホルモンの変化
- (一社)日本てんかん学会, Sep. 2018, てんかん研究, 36(2) (2), 324 - 324, Japanese難治性てんかん重積治療と予後について 三次診療施設における小児のけいれん重積治療と予後
- 日本先天代謝異常学会, Sep. 2018, 日本先天代謝異常学会雑誌, 34, 201 - 201, Japanese7歳時に診断した若年/成人型ガラクトシアリドーシスの臨床経過
- 01 Aug. 2018, 子どもの心とからだ, 27(2) (2), 318, Japanese保育を治療構造に取り入れた小児科病棟での摂食障害入院治療の試み
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S202 - S202, Japaneseけいれんの第一選択薬はジアゼパム? それともミダゾラム?
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S204 - S204, Japaneseけいれん重積治療における持続脳波モニタリング
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S325 - S325, Japaneseサイトカインストームによる急性脳症が予測される小児に対するステロイドパルス療法の有効性
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S327 - S327, Japanese急性散在性脳脊髄炎24例における発症から軽快までの経時的な臨床経過の特徴
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S333 - S333, Japanese小児救急外来における非けいれん性発作を示す小児患者の臨床的特徴
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S352 - S352, Japanese神戸大学における小児科と麻酔科の連携による脊髄性筋萎縮症のヌシネルセン治療
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S431 - S431, Japanese複雑型熱性けいれんの急性期の臨床経過の特徴
- (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S432 - S432, Japanese発熱に伴う難治性てんかん重積状態に対するバルビツレート昏睡療法の最適な鎮静深度に関する多施設共同研究
- (株)日本小児医事出版社, May 2018, 小児科臨床, 71(5) (5), 790 - 801, Japanese私の処方2018 V.神経・筋疾患の処方 4.急性脳症の管理
- 01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 809, Japaneseカーボカウントが1型糖尿病の血糖管理に有用であった7歳男児例
- 01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 816, Japanese先天性甲状腺機能低下症(CH)のフォロー中に偽性副甲状腺機能低下症と診断された1例
- 01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 820, Japanese不明熱の精査中にRadiologically Isolated Syndromeが疑われた1例
- 01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 813, Japanese一過性意識消失発作を主訴に小児神経外来を受診した45例の検討
- (公社)日本小児科学会, Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 808 - 809, Japanese乳幼児感覚プロファイルを用いた発達障害児の感覚特性に関する検討
- 01 Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 460, Japanese2歳時に早期診断が出来た脊髄性筋萎縮症3a型の女児例
- 2018, 日本小児内分泌学会学術集会プログラム・抄録集, 52nd, 228, Japanese発作性運動誘発性ジスキネジアを呈した偽性副甲状腺機能低下症の一例
- 2018, 日本眼感染症学会・日本眼炎症学会・日本コンタクトレンズ学会総会・日本涙道・涙液学会プログラム・講演抄録集, 55th-52nd-61st-7th, 97, Japanese3歳女児に生じたVogt‐小柳‐原田病疑い症例
- 01 Oct. 2017, 小児の精神と神経, 57(3) (3), 227, Japanese乳幼児期における発達障害特性と感覚特性との関連についての検討
- 12 Sep. 2017, 日本先天代謝異常学会雑誌, 33, 202, Japaneseカルニチンのみで良好な経過をたどる慢性進行型メチルマロン酸血症同胞例
- The Japanese Society of Child Neurology, 01 Sep. 2017, 脳と発達, 49(5) (5), 327‐331 - 331, Japanese
Objective: Although targeted temperature management (TTM) has been reported to improve the outcomes of children with refractory status epilepticus and fever, some TTM-treated children exhibit poor outcomes. We aimed to explore the initial clinical characteristics of children with prognostic symptoms who underwent TTM for refractory status epilepticus and fever. Methods: We retrospectively reviewed the clinical records of 5 children with refractory status epilepticus and fever who underwent TTM at the Kakogawa East City Hospital and Hyogo Children's Hospital from 2010-2015. We compared the initial clinical characteristics of the children with and without prognostic symptoms. Results: Two patients with prognostic symptoms showed impaired consciousness with dilated pupils after convulsion cessation, and they were suspected to have non-convulsive status epilepticus (NCSE). The time between the first-line treatment of diazepam infusion and the second-line treatment of midazolam administration was longer in children with prognostic symptoms than in those without. Conclusions: Children with refractory status epilepticus, fever, and dilated pupils after convulsion cessation had prognostic symptoms and longer delays before second-line treatment. Typically, the outcomes of refractory status epilepticus and fever depend on the underlying disease, but it was believed here that protraction of NCSE and a delay in the additional treatment might have been related to the poor outcomes.
- 01 May 2017, 日本小児科学会雑誌, 121(5) (5), 908‐909, JapaneseビタミンB12反応性メチルマロン酸血症の1例
- 01 May 2017, 日本小児科学会雑誌, 121(5) (5), 912, Japanese点頭てんかん再発例に対しケトン食療法とACTH反復投与を行った1例
- 01 May 2017, 日本小児科学会雑誌, 121(5) (5), 904, Japanese熱性けいれん重積に対するミダゾラム静注と持続静注療法の比較検討
- 01 May 2017, 日本小児科学会雑誌, 121(5) (5), 902‐903, Japanese間質性肺炎を合併したエンテロウイルスD68型感染症の1例
- 01 May 2017, 日本小児科学会雑誌, 121(5) (5), 906, Japanese眼瞼下垂の経過観察中に詳細な問診により明らかになった両側性腱膜性眼瞼下垂の1例
- 28 Feb. 2017, 小児の脳神経, 42(1) (1), 21‐27, JapaneseNonconvulsive seizures in pediatric neurointensive care
- (公社)日本小児科学会, 01 Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 374 - 374, Japanese超低出生体重児のSGA性低身長症に対する成長ホルモン治療の検討
- 01 Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 380, Japanese近位筋優位の筋力低下から筋疾患が疑われたシャルコー・マリー・トゥース病2型
- 01 Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 261, JapaneseDigenicな変異で発症した,致死性不整脈と心筋緻密化障害を認めた兄弟例
- 2017, 日本集中治療医学会学術集会(Web), 44th, ROMBUNNO.O3‐3 (WEB ONLY), Japanese当院における重症熱性けいれんの後ろ向きコホート研究
- 2017, 日本小児精神神経学会プログラム・抄録集, 117th, 49, Japanese乳幼児期における発達障害特性と感覚特性との関連についての検討
- 2017, 日本小児内分泌学会学術集会プログラム・抄録集, 51st, 207, Japanese新生児期に高TSH血症を示した偽性副甲状腺機能低下症の乳児期BMI
- 01 Oct. 2016, 小児の精神と神経, 56(3) (3), 257‐258, Japanese極低出生体重児と自閉スペクトラム症児の発達特徴の比較―マッチドケースコントロール研究―
- 30 Sep. 2016, 日本先天代謝異常学会雑誌, 32, 191, JapaneseビタミンB12反応性を認めた軽症メチルマロニルCoAムターゼ欠損症の一例
- 02 Sep. 2016, てんかん研究, 34(2) (2), 460, JapaneseAST上昇を認めない重症熱性けいれん小児における非けいれん性発作―長期予後の検討
- 14 Jun. 2016, 日本小児救急医学会雑誌, 15(2) (2), 245, Japanese間質性肺炎を発症したエンテロウイルスD68感染症の1例
- 日本小児医事出版社, 05 Jun. 2016, 小児科臨床, 69(6) (6), 1101‐1106 - 1106, Japanese15番染色体長腕近位部の重複を持つ7症例の細胞遺伝学的および臨床的所見
- 05 Jun. 2016, 小児神経学の進歩, 45, 111‐124, Japanese〈小児神経の救急〉急性脳炎・脳症の管理
- Jun. 2016, 小児神経学の進歩, 45, 111 - 124, Japanese小児神経の救急 急性脳炎・脳症の管理[Invited]Introduction other
- (一社)日本小児神経学会, May 2016, 脳と発達, 48(Suppl.) (Suppl.), S285 - S285, Japanese
- 01 Feb. 2016, 日本小児科学会雑誌, 120(2) (2), 519, JapaneseNCSEを伴うAESDの特徴を示した敗血性脳症の一例
- 2016, 日本小児精神神経学会プログラム・抄録集, 115th, 40, Japanese極低出生体重児と自閉スペクトラム症児の発達特徴の比較―マッチドケースコントロール研究―
- 2016, 日本小児遺伝学会学術集会プログラム・抄録集, 39th, 52, Japanese重篤な経過を呈した,両親由来の異なる心筋障害遺伝子の変異を受け継いだ兄弟例
- (公社)日本小児科学会, Jan. 2016, 日本小児科学会雑誌, 120(1) (1), 78 - 78, Japaneseショック状態で搬送された小腸軸捻転の1救命例
- 01 Jan. 2016, 日本小児科学会雑誌, 120(1) (1), 86, Japaneseインフルエンザ関連神経症状を呈した小児の臨床的特徴―2014~2015年シーズンでの検討
- 17 Sep. 2015, てんかん研究, 33(2) (2), 404, Japanese小児救急集中治療領域における非けいれん性発作
- Jul. 2015, 日本先天異常学会学術集会プログラム・抄録集, 55th, 95, JapaneseTruSight Oneシークエンスパネルで原因遺伝子を同定した神経発達疾患の3例
- May 2015, 脳と発達, 47(Suppl.) (Suppl.), S226, Japanese幼児期に発症した多発性硬化症の4例Meeting report
- 日本小児医事出版社, 05 Apr. 2015, 小児科臨床, 68(4) (4), 733 - 741, Japanese私の処方2015 V.神経・筋疾患の処方 4.急性脳症の管理
- 31 Mar. 2015, 兵庫県医師会医学雑誌, 57(2) (2), 66 - 67, Japanese小児重症熱性けいれんに対する脳低温/平温・バルビツレート昏睡療法の早期導入は急性脳症への進展を阻止し,神経学的予後を改善するか?
- 日本小児科学会, 01 Oct. 2014, 日本小児科学会雑誌, 118(10) (10), 1475 - 1480, JapaneseNonconvulsive Seizures in Children with Prolonged Febrile Seizures
- 01 Jun. 2014, 日本小児科学会雑誌, 118(6) (6), 969, Japanese急性脳症治療を目指した一般人口研究のための予備的研究
- 日本小児科学会, 01 May 2014, 日本小児科学会雑誌, 118(5) (5), 812 - 818, JapaneseA Case of Acute Encephalopathy with Secondary Carnitine Deficiency after Taking Pivalate-conjugated Antibiotics for 3 Days
- 01 Feb. 2014, 日本小児科学会雑誌, 118(2) (2), 232, Japanese神経学的基礎疾患を有する症例における急性脳症での神経学的後遺症の予測
- 01 Feb. 2014, 日本小児科学会雑誌, 118(2) (2), 334, Japanese組織ドップラー心エコーにて心機能低下が判明した一般小児科症例
- 日本小児医事出版社, 05 Sep. 2013, 小児科臨床, 66(9) (9), 1887 - 1891, Japanese小児集中治療領域における自動発作検出プログラムの応用
- 日本小児科学会, 01 Jun. 2013, 日本小児科学会雑誌, 117(6) (6), 986 - 991, JapaneseNon-convulsive Seizures in Children with an Altered Mental State Associated with Influenza A (H1N1) pdm09 Infection
- Feb. 2013, NEUROLOGY, 80, EnglishInduced Hypothermia/Normothermia with General Anesthesia Is Related to Better Outcomes in Children with Acute Encephalopathy Caused by ExcitotoxicitySummary international conference
- 01 Feb. 2013, 日本小児科学会雑誌, 117(2) (2), 349, Japanese急性脳症における神経学的短期および長期予後の比較
- 診断と治療社, 01 May 2012, 小児科診療, 75(5) (5), 851 - 858, Japanese研修医のための神経学的診察テクニック II.よくある主訴と診療の実際 頭部外傷
- 01 Feb. 2012, 日本小児科学会雑誌, 116(2) (2), 312, Japanese精神症状を主訴に救急入院となった非ヘルペス性急性辺縁系脳炎の2例
- (NPO)日本小児がん学会, Nov. 2011, 日本小児血液・がん学会学術集会・日本小児がん看護学会・がんの子供を守る会公開シンポジウムプログラム・総会号, 48(プログラム・総会号) (プログラム・総会号), 225 - 225, Japanese卵巣奇形腫に合併した抗NMDA受容体脳炎に対し腫瘍摘出術,免疫療法が著効した女児例
- Nov. 2011, No To Hattatsu, 43(6) (6), 459 - 463, Japanese
- 20 May 2011, 日本小児放射線学会雑誌, 27, 18, Japanese急激な症状の悪化を認めたインフルエンザ脳症の3例
- 01 Mar. 2011, 小児内科, 43(3) (3), 333 - 336, Japanese全面改訂版 必携!けいれん,意識障害―その時どうする〈けいれん重積への救急対応〉ミダゾラムの使い方と注意点
- (一社)日本小児救急医学会, Mar. 2011, 日本小児救急医学会雑誌, 10(1) (1), 22 - 26, JapaneseComparison of the neurological outcomes after treatments with mild hypothermia with dexamethasone and normothermia for presumed encephalitis/ acute encephalopathy in children
- 01 Feb. 2011, 日本小児科学会雑誌, 115(2) (2), 355, Japanese我が国における乳幼児頭部外傷例の虐待通告基準の検証
- 24 Jan. 2011, 日本集中治療医学会雑誌, 18(Supplement) (Supplement), 327, Japanese重症頭部外傷の経過中に横紋筋融解症を来たした小児の1例
- 01 Dec. 2010, 日本小児科学会雑誌, 114(12) (12), 1946, Japanese兵庫県立こども病院小児救急医療センターにおける2年間の人工呼吸管理患者156症例の検討
- 01 Dec. 2010, 日本小児科学会雑誌, 114(12) (12), 1941, Japaneseてんかんとして治療された転換性障害の1例
- メディカ出版, 01 Oct. 2010, Emerg Care, 23(10) (10), 1033 - 1039, Japanese救急医療チームがおさえておきたい診断・治療・予防のポイント どう診る?どう対応する?乳幼児の頭部外傷と虐待 5 AHTの診断 その基準と社会的介入の視点から理解する意味
- (一社)日本小児救急医学会, Oct. 2010, 日本小児救急医学会雑誌, 9(3) (3), 321 - 324, JapaneseIndications for Computed Tomography Scan in Children with Head Injury
- メディカ出版, 01 Jul. 2010, Emerg Care, 23(7) (7), 741 - 747, Japanese救急医療チームがおさえておきたい診断・治療・予防のポイント どう診る?どう対応する?乳幼児の頭部外傷と虐待 2 AHTを疑うプロセスのポイント 虐待の可能性に気付き確信を得るために
- (公社)日本小児科学会, May 2010, 日本小児科学会雑誌, 114(5) (5), 858 - 864, JapaneseTherapeutic Indication for Acute Encephalopathy Using Predictors in Patients with Complex Febrile Seizures
- 01 Feb. 2010, 日本小児科学会雑誌, 114(2) (2), 190, Japaneseexcitotoxicityが想定される急性脳炎・脳症に対する脳低温・平温療法の効果
- 01 Feb. 2010, 日本小児科学会雑誌, 114(2) (2), 177, Japanese当院救急集中治療科における院外心肺停止症例の検討
- 01 Feb. 2010, 日本小児科学会雑誌, 114(2) (2), 176, Japaneseイレウスにおける緊急手術の適応を判断すべき臨床所見
- Jan. 2010, No To Hattatsu, 42(1) (1), 23 - 28, Japanese
- 01 Dec. 2009, 日本小児科学会雑誌, 113(12) (12), 1900 - 1901, JapaneseHHV‐6による痙攣重積型脳症と薬剤性過敏症症候群の1例
- 01 Dec. 2009, 日本小児科学会雑誌, 113(12) (12), 1900, Japanese連続脳波モニタリングでてんかん重積状態が明らかとなった急性脳症疑いの1例
- (公社)日本小児科学会, Dec. 2009, 日本小児科学会雑誌, 113(12) (12), 1814 - 1819, JapaneseClinical Features of Inflicted Head Injury in Children Aged under 2 Years of Age
- 19 Jun. 2009, 日本小児救急医学会雑誌, 8(2) (2), 227, Japanese頭部外傷患者に対する頭部CTの検討
- 日本小児医事出版社, 05 Mar. 2009, 小児科臨床, 62(3) (3), 475 - 480, Japanese持続脳波モニタリング下での集中管理によって予後良好であった「特異な脳炎・脳症後てんかんの一群」の男児例
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 607 - 607, Japanese前頭葉を主として障害する乳幼児急性脳症(AIEF)の1例
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 597 - 597, Japanese当院救急医療室における痙攣性疾患のまとめ
- 01 Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 597, Japanese当院救急医療室における院外心肺停止症例の検討
- (公社)日本小児科学会, Mar. 2009, 日本小児科学会雑誌, 113(3) (3), 601 - 601, JapanesePICUにおける集中治療を要した中枢神経疾患の検討
- 2009, 発達期に発生する外因性脳障害の診断・治療予防のための実証的研究とガイドライン作成 平成18-20年度 総括研究報告書 ガイドライン資料, 90 - 94, Japanese「発達期に発生する外因性脳障害の診断・治療予防のための実証的研究とガイドライン作成」D‐2 Shaken Baby Syndromeの発生機序および疫学,発見,診断,介入に関する研究(2)
- 2009, 発達期に発生する外因性脳障害の診断・治療予防のための実証的研究とガイドライン作成 平成18-20年度 総括研究報告書 ガイドライン資料, 98,100-151, Japanese「発達期に発生する外因性脳障害の診断・治療予防のための実証的研究とガイドライン作成」「虐待が疑われる乳幼児頭部外傷(Abusive head trauma in infants and young children,AHT)」の診断・治療・予防の手引き
- 2009, 発達期に発生する外因性脳障害の診断・治療予防のための実証的研究とガイドライン作成 平成18-20年度 総括研究報告書 ガイドライン資料, 75 - 89, Japanese「発達期に発生する外因性脳障害の診断・治療予防のための実証的研究とガイドライン作成」D‐1 Shaken Baby Syndromeの発生機序および疫学,発見,診断,介入に関する研究(1)
- 10 Oct. 2008, 臨床研修プラクティス, 5(11) (11), 50-57,102, Japanese小児科ER~これだけは見逃さない~III.症状からみた見逃してはいけない疾患 4 痙攣している
- (一社)日本救急医学会, Aug. 2008, 日本救急医学会雑誌, 19(8) (8), 734 - 734, Japanese小児心肺停止蘇生後症例の神経学的予後判定における聴性脳幹反応(ABR)V波の検討
- (一社)日本小児救急医学会, Jun. 2008, 日本小児救急医学会雑誌, 7(1) (1), 94 - 94, Japanese当院における有熱性痙攣の検討
- (一社)日本小児救急医学会, Jun. 2008, 日本小児救急医学会雑誌, 7(1) (1), 110 - 110, Japanese小児重症頭部外傷に対し,減圧開頭術を併用した脳低温療法施行症例の検討
- 01 Feb. 2008, 日本小児科学会雑誌, 112(2) (2), 279, Japanese当院救急医療室において救命不可能であった児への対応
- (公社)日本小児科学会, Jan. 2008, 日本小児科学会雑誌, 112(1) (1), 73 - 73, Japanese頭蓋内圧モニタリングを併用し脳低温療法を施行したCPA蘇生後の1症例
- (一社)日本集中治療医学会, Jan. 2008, 日本集中治療医学会雑誌, 15(Suppl.) (Suppl.), 179 - 179, Japanese
- 31 Dec. 2007, 小児の脳神経, 32(6) (6), 430 - 438, JapaneseA Comprehensive Approach to Abusive Head Trauma of Children Younger than 2 Years of Age
- 眼科臨床医報会, 15 Dec. 2007, 眼科臨床医報, 101(12) (12), 1184 - 1188, Japaneseムンプス感染症を契機に発症した小児視神経症の1例
- Japan Epilepsy Society, 30 Sep. 2007, てんかん研究, 25(3) (3), 354 - 354, Japanese持続脳波モニタリング下での集中管理により予後良好であった「特異な脳炎・脳症後てんかんの一群」の男児例
- 20 Sep. 2007, 日本小児保健学会講演集, 54th, 129, Japanese人工死産率は地域所得格差を反映する―県民所得と母子保健統計から―
- (一社)日本救急医学会, Aug. 2007, 日本救急医学会雑誌, 18(8) (8), 565 - 565, Japanese小児脳低温療法における頭蓋内圧センサー挿入症例の検討
- 15 Jun. 2007, 日本小児救急医学会雑誌, 6(1) (1), 129, Japanese当院救急医療室における救命不可能であった児への対応 その1―中枢神経機能評価と治療適応に関する現状―
- 15 Jun. 2007, 日本小児救急医学会雑誌, 6(1) (1), 69, Japanese小児脳低温療法症例における頭蓋内圧および脳還流圧の経時的変化に関する検討
- (公社)日本小児科学会, Feb. 2007, 日本小児科学会雑誌, 111(2) (2), 355 - 355, Japanese乳幼児頭部外傷の虐待判断指標作成の試み:入院した乳幼児41例の検討
- 01 Feb. 2007, 日本小児科学会雑誌, 111(2) (2), 357, Japanese兵庫県立こども病院における小児脳低温療法の現況
- 31 Jan. 2007, 日本集中治療医学会雑誌, 14(Supplement) (Supplement), 231, Japanese兵庫県立こども病院における小児脳低温療法の現況
- 2007, 日本小児感染症学会総会・学術集会プログラム・抄録集, 39th, 163, Japanese麻疹風疹(MR)混合ワクチン接種後に急性脳炎をきたした1症例
- (公社)日本小児科学会, Jan. 2007, 日本小児科学会雑誌, 111(1) (1), 104 - 104, JapaneseTBI(traumatic brain injury)で来院し虐待が疑われた乳幼児16例
- 01 Jan. 2007, 日本小児科学会雑誌, 111(1) (1), 99, Japanese被虐待児への対応に関する院内・院外連携システムに関する研究
- (公社)日本小児科学会, 01 Feb. 2006, 日本小児科学会雑誌, 110(2) (2), 339 - 339, Japanese子どものための禁煙治療の普及を目指して
- 2006, 発達期に発症する外因性脳障害の診断・治療ガイドラインに関する臨床的実証研究 平成17年度 総括研究報告書・ガイドライン暫定案資料, 47 - 49, JapaneseClinical, empirical studies concerning diagnostics and guidelines for traumatic brain injuries in children and adolescents. Diagnostic guideline for Shaken Baby Syndrome (SBS).
- 2006, 発達期に発症する外因性脳障害の診断・治療ガイドラインに関する臨床的実証研究 平成17年度 総括研究報告書・ガイドライン暫定案資料, 140 - 142, JapaneseClinical, empirical studies concerning diagnostics and guidelines for traumatic brain injuries in children and adolescents. Guideline for diagnostics of Shaken Baby Syndrome (SBS).
- 2005, 被虐待児の医学的総合治療システムに関する研究 平成17年度 研究報告書, 81 - 92, Japanese被虐待児への医学的総合治療システムのあり方に関する研究 被虐待児に対応するための病院内および地域医療システムに関する研究 兵庫県内の被虐待児に対するための病院内および地域医療システムに関する現状と課題
- 2005, 被虐待児に対応するための病院内および地域医療システムに関する研究 平成15-17年度 被虐待児への医学的総合治療システムのあり方に関する研究, 70 - 75, Japanese被虐待児に対応するための病院内および地域医療システムに関する研究 被虐待児への医学的総合治療システムのあり方に関する研究 被虐待児への対応に関する院内・院外連携システムに関する研究―兵庫県の結果からみえてきたもの―平成17年度
- 01 Jan. 2004, 日本小児科学会雑誌, 108(1) (1), 37 - 44, JapaneseClinical Survey of Children in Developmental Behavioral Pediatric Clinic of Kobe University Hospital
- 01 Dec. 2003, 日本小児科学会雑誌, 107(12) (12), 1697, Japanese心身症としてフォローを受けていたもやもや病の1例
- 01 Dec. 2003, 日本小児科学会雑誌, 107(12) (12), 1694, Japanese起立性調節障害を伴った不登校の児の背景と予後
- 01 Dec. 2003, 日本小児科学会雑誌, 107(12) (12), 1697, Japanese小児療養環境特別加算の利用状況と今後の問題点
- 05 Sep. 2003, 日本小児心身医学会プログラム・抄録集, 21st, 54, Japanese起立性調節障害を伴った不登校の児の背景と予後
- 01 Feb. 2003, 日本小児科学会雑誌, 107(2) (2), 302, Japanese子どもの精神的・心理社会的問題を対象とした大学病院小児科専門外来の統計
- 2002, 日本小児臨床薬理学会雑誌, 15(1) (1), 145 - 148, Japanese小児科臨床におけるADHDの診断とmethylphenidateによる薬物治療の問題点―1997‐2000年の神戸大学医学部附属病院小児科発達行動外来での臨床経験から
- 01 Dec. 2001, 日本小児科学会雑誌, 105(12) (12), 1401, Japanese2000年初診のADHD児の背景
- 30 Nov. 2001, 周産期医学, 31, 824 - 826, Japaneseチャイルドカーシート
- 日本てんかん学会, 2001, 日本てんかん学会プログラム・予稿集, (35) (35), 165 - 165, JapaneseE-8 成人期にキャリーオーバーした小児てんかん例の検討
- 01 Jan. 2001, 日本小児科学会雑誌, 105(1) (1), 53, Japanese出生直後より長時間の心肺停止状態の持続が推測されたが,著明な低体温のために救命し得た墜落産の1例
- 01 Jan. 2001, 日本小児科学会雑誌, 105(1) (1), 56, Japanese胎児期に多房性嚢胞で発見された気管支原性嚢胞の1例
- 01 Feb. 2000, 日本小児科学会雑誌, 104(2) (2), 219, Japaneseチャイルドシートが新生児のDesaturationに及ぼす影響
- 01 Jan. 2000, 日本小児科学会雑誌, 104(1) (1), 93, Japanese不明熱で発症した多発性肝膿ようの1例 第217回日本小児科学会兵庫県地方会
- 20 Oct. 1999, 日本未熟児新生児学会雑誌, 11(3) (3), 416, Japaneseチャイルドシートが新生児の呼吸機能に及ぼす影響について
- 第52回日本てんかん学会学術集会, Oct. 2018, Japanese, Domestic conference1. 三次診療施設における小児のけいれん重積治療と予後Oral presentation
- 第275回日本小児科学会兵庫県地方会, Sep. 2018, Japanese, Domestic conference2. 熱性けいれん・急性脳症におけるけいれん重積の管理Oral presentation
- 第27回臨床内分泌代謝Update, Nov. 2017, Japanese, 日本内分泌学会, 神戸, Domestic conferenceCGMが診断・治療に有用であったダンピング症候群の乳児例Poster presentation
- 日本小児神経学会近畿地方会, Oct. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference症候性PKDを呈した偽性副甲状腺機能低下症の8歳女児例Oral presentation
- 第59回日本先天代謝異常学会, Oct. 2017, Japanese, 日本先天代謝異常学会, 埼玉, Domestic conferenceカルニチンのみで良好な経過をたどる慢性進行型メチルマロン酸血症同胞例Poster presentation
- 第272回日本小児科学会兵庫県地方会, Sep. 2017, Japanese, 日本小児科学会, 姫路, Domestic conference不明熱の精査中にRadiologically Isolated Syndromeが疑われた1例Oral presentation
- 第51回日本小児内分泌学会, Sep. 2017, Japanese, 日本小児内分泌学会, 大阪, Domestic conference新生児期に高TSH血症を示した偽性副甲状腺機能低下症の乳児期BMIPoster presentation
- 第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference有熱性けいれん重積症例におけるAESDおよび急性脳症鑑別のためのAESD prediction scoreの有用性の検証Oral presentation
- 第117回日本小児精神神経学会, Jun. 2017, Japanese, 日本小児神経学会, 東京, Domestic conference乳幼児期における発達障害特性と感覚特性との関連についての検討Oral presentation
- 第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference乳幼児期における発達障害児の感覚特性についての検討～自閉症および知的障害特性との関連～Oral presentation
- 第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference小児難治てんかん重積状態に対するチアミラールを用いた全身麻酔療法Oral presentation
- 第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference三次救急医療施設における脳炎脳症の治療戦略-治療内容と治療開始時期の選択-[Invited]Nominated symposium
- 第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conferenceTargeted temperature managementを導入した急性脳症疑い症例における早期予後因子の検討Oral presentation
- 第60回日本糖尿病学会年次学術集会, May 2017, Japanese, 日本糖尿病学会, 名古屋, Domestic conference幼児期からの糖・脂質代謝の経過をフォローしえたPTRF遺伝子変異による全身性脂肪萎縮症の一例（ポスター発表）Poster presentation
- 第60回日本糖尿病学会年次学術集会, May 2017, Japanese, 日本糖尿病学会, 名古屋, Domestic conference幼児期からの糖・脂質代謝の経過をフォローしえたPTRF 遺伝子変異による全身性脂肪萎縮症の一例Oral presentation
- 第61回 日本小児神経学会近畿地方会, May 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference不明熱を契機にRadiologically Isolated Syndromeを呈した1例Oral presentation
- 270回 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 尼崎, Domestic conference乳幼児感覚プロファイルを用いた発達障害児の感覚特性に関する検討Oral presentation
- 第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conference超低出生体重児のSGA性低身長症に対する成長ホルモン治療の検討Poster presentation
- 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 神戸, Domestic conference先天性甲状腺機能低下症（CH）のフォロー中に偽性副甲状腺機能低下症と診断された1例Oral presentation
- 第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conference近位筋優位の筋力低下から筋疾患が疑われたシャルコー・マリー・トゥース病2型Poster presentation
- 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 神戸, Domestic conference一過性意識消失発作を主訴に小児神経外来を受診した45例の検討Oral presentation
- 270回 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 尼崎, Domestic conferenceカーボカウントが1型糖尿病の血糖管理に有用であった7歳男児例Oral presentation
- 第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conferenceDigenicな変異で発症した、致死性不整脈と心筋緻密化障害を認めた兄弟例Poster presentation
- 14th Asian and Oceanian Congress of Child Neurology, May 2017, English, Fukuoka, Japan, International conferenceComparison of the efficacy and complications of fosphenytoin versus continuous midazolam in children with febrile status epilepticusOral presentation
- 14th Asian and Oceanian Congress of Child Neurology, May 2017, English, Fukuoka, Japan, International conferenceCase series of fatal acute encephalopathyPoster presentation
- Pediatric Academic Societies Meeting 2017, May 2017, English, American Pediatric Society, San Francisco, USA, International conferenceBrain magnetic resonance imaging findings in Infants with congenital cytomegalovirus infection early in lifePoster presentation
- 日本小児遺伝学会, Dec. 2016, Japanese, 日本小児遺伝学会, 東京, Domestic conference重篤な経過を呈した、両親由来の異なる心筋障害遺伝子の変異を受け継いだ兄弟例Oral presentation
- 12nd Congress for Asian Society for Pediatric Research 2016, Nov. 2016, English, Congress for Asian Society for Pediatric Research, Bangkok, Thailand, International conferenceA pediatric patient with interstitial pneumonia due to enterovirus D68.Poster presentation
- 第60回日本小児神経学会近畿地方会, Oct. 2016, Japanese, 日本小児神経学会, 大阪, Domestic conference熱性けいれん重積に対するミダゾラム静注と持続静注療法の比較検討Oral presentation
- 第58回先天代謝異常学会, Oct. 2016, Japanese, 日本先天代謝異常学会, 東京, Domestic conferenceビタミンB12反応性を認めた軽症メチルマロニルCoAムターゼ欠損症の一例Poster presentation
- 第50回日本てんかん学会学術集会, Oct. 2016, Japanese, 日本てんかん学会, 静岡, Domestic conferenceAST 上昇を認めない重症熱性けいれん小児における非けいれん性発作―長期予後の検討Oral presentation
- 第60回日本小児神経学会近畿地方会, Oct. 2016, Japanese, 日本小児神経学会, 大阪, Domestic conference3歳児より筋力低下を呈したシャルコリー・マリー・トゥース病2型の一例Oral presentation
- 第 269 回 日本小児科学会兵庫県地方会, Sep. 2016, Japanese, 日本小児科学会兵庫県地方会, 姫路, Domestic conference点頭てんかん再発例に対しケトン食療法とACTH反復投与を行った一例Oral presentation
- Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Sep. 2016, English, EUROPEAN COMMITTEE FOR TREATMENT AND RESEARCH IN MULTIPLE SCLEROSIS, London, UK, International conferenceInterferon beta-1a therapy for multiple sclerosis diagnosed in early childhoodPoster presentation
- 第30回日本小児救急医学会学術集会, Jul. 2016, Japanese, 日本小児救急医学, 仙台, Domestic conference間質性肺炎を発症したエンテロウイルスD68感染症の一例Poster presentation
- 18th Annual Meeting of Infantile Seizure Society, Jul. 2016, English, Infantile Seizure Society, 東京, International conferenceEfficacy and CNS depression of second–line treatment in children with febrile status epilepticusOral presentation
- 18th Annual Meeting of Infantile Seizure Society, Jul. 2016, English, International Symposium on Acute Encephalopathy in Infancy and Its Related Disorders, 東京, International conferenceCase series of fatal acute encephalopathyPoster presentation
- 第58回日本小児神経学会学術集会, Jun. 2016, Japanese, 日本小児神経学会, 東京, Domestic conference先天性サイトメガロウイルス感染症児における生後早期の頭部MRI所見Oral presentation
- 第115回日本小児精神神経学会, Jun. 2016, Japanese, 日本小児精神神経学会, 横浜, Domestic conference極低出生体重児と自閉スペクトラム症児の発達特徴の比較―マッチドケースコントロール研究―Oral presentation
- 第58回日本小児神経学会学術集会, Jun. 2016, Japanese, 日本小児神経学会, 東京, Domestic conference急性脳症治療における全身麻酔療法導入時のチアミラール投与の検討Oral presentation
- 第58回日本小児神経学会学術集会, Jun. 2016, Japanese, 日本小児神経学会, 東京, Domestic conference急性脳症による死亡例の検討Oral presentation
- 第58回日本小児神経学会学術集会, Jun. 2016, Japanese, 日本小児神経学会, 東京, Domestic conferenceジストロフィン遺伝子イントロン64のスプライス供与部位の変異（c.9361+1 G>A）により発症したDuchenne型筋ジストロフィーの一例Oral presentation
- 第268回日本小児科学会兵庫県地方会, May 2016, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conference眼瞼下垂の経過観察中に詳細な問診により明らかになった両側性腱膜性眼瞼下垂の一例Oral presentation
- 第268回日本小児科学会兵庫県地方会, May 2016, Japanese, 日本小児科学会兵庫県地方会, 神戸, Domestic conferenceビタミンB12反応性メチルマロン酸血症の一例Oral presentation
■ Research Themes
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2021 - 31 Mar. 2025Elucidation of pathophysiology and trigger of AESD using EEG, inflammatory markers, and cerebral blood flow analysis.今年度は、既存の症例において、発症（＝神経症状出現）からの経過時刻を記録した臨床データベースを用いて、発症から48時間以内の採取時刻が特定できた血清を用いてサイトカインの測定を行った。今年度の補助金は主にこのサイトカイン測定費用が充てられた。 対象はけいれん重積型急性脳症（AESD）4例、熱性けいれん（FS）21例。FSは有熱性のけいれん発作を認めるも後遺症なしの症例であった。測定はBio-Plexマルチプレックスイムノアッセイ法で行った。 一部のサイトカインについて結果を示す（単位は全て中央値pg/mL）。発症後0~24時間以内の検体（AESD群3例（6検体)、FS群20例（29検体））において、抗炎症性サイトカインであるIL-1Ra（AESD群 : 30486, FS群 : 3209）、IL-10（AESD群 : 85, FS群 : 21）はFSと比較してAESD群において有意に高値であった。炎症性サイトカインであるIL-1β（AESD群 : 5.1, FS群 : 1.3）とIL-6（AESD群 : 134, FS群 : 17）では明らかな違いを認めなかった。 発症後0~48時間以内の検体（AESD群4例（10検体)、FS群20例（30検体））では、抗炎症性サイトカインIL-1Ra（AESD群 : 4162, FS群 : 3388）、IL-10（AESD群 : 39, FS群 : 19）、炎症性サイトカイン IL-1β（AESD群 : １.１, FS群 : 1.3）とIL-6（AESD群 : １８, FS群 : 1８）といずれのサイトカインにおいても明らかな違いを認めなかった。 炎症性サイトカイン、抗炎症性サイトカインいずれも発症２４時間以内にピークを認め、抗炎症性サイトカインにおいてのみAESDとFSの違いが捉えられることが示唆された。 またAESDとFSの発症初期の脳波を取得し解析を開始した。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2018 - 31 Mar. 2021Elucidation of the pathophysiology of refractory status epilepticus by comprehensive inflammation analysis and development of new diagnosis and treatment methodsFebrile status epilepticus (FSE) and refractory FSE (fRSE) are common in pediatric emergency, and are often diagnosed as acute encephalopathy with serious outcomes such as death and sequelae. In this study, we found that in pediatric patients with fRSE, inflammatory cytokines peaked within 24 hours of onset and then decreased, regardless of the final diagnosis or outcome. We also revealed that the inflammation-related protein GDF15 reported as an excellent pathological and prognostic markers such as sepsis was also significantly elevated in FSE, peaked out within 12 hours of onset. Furthermore, the peak value of GDF-15 within 6 hours of onset was shown to be associated with the neurological sequelae in children with FSE.