Mitsuaki Hosoya

Fukushima Medical University, Hukusima, Fukushima, Japan

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Publications (143)279.42 Total impact

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    ABSTRACT: We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg peramivir. Sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-polymerase chain reaction and neuraminidase inhibition assay. The peramivir concentration in serum and URT after a single administration at 10 mg/kg was measured and the predictive blood and URT peramivir concentration-time curve was determined to assess various administration regimens against resistant variants. The serum peramivir concentration decreased to <0.1% of Cmax at 24 h after administration. Rapid elimination of peramivir from URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of decrease in susceptibility to peramivir. A longer maintenance of high level of peramivir in URT is expected by divided administration rather than once daily administration. When no clinical improvement is observed in patients with normal-susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events is expected by divided administration rather than the once daily administration with an increased dosage. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 12/2014; · 4.45 Impact Factor
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    ABSTRACT: Background The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced people to evacuate their hometowns. Many evacuees from the government-designated evacuation zone were forced to change their lifestyle, diet, exercise, and other personal habits. The Comprehensive Health Check (CHC), 1 of 4 detailed surveys of The Fukushima Health Management Survey (FHMS), was implemented to support the prevention of lifestyle-related disease. The aim of this study was to analyze changes in red blood cell count (RBC), hemoglobin (Hb) levels, and hematocrit (Ht) levels by comparing data from the medical health checkup before and after the disaster in individuals who were 40 years old or older. Methods Subjects in this study were Japanese men and women living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima prefecture. Annual health checkups with a focus on metabolic syndrome for insured persons/dependents aged 40 or older by Health Care Insurers have been conducted since 2008. All analyses in this study were limited to men and women aged 40-90 years. Changes in RBC, Hb levels, Ht levels, and prevalence of polycythemia before and after the disaster were compared. Results First, RBC, Hb, and Ht significantly increased in both men and women evacuees. The evacuation was significantly associated with increased Hb levels after adjustment for age, gender, smoking status, excess ethanol intake, BMI, and baseline Hb level (beta = 0.16, p < 0.001). Furthermore, the prevalence of polycythemia stratified by smoking status or obesity also increased in the evacuee group. Conclusions To our knowledge, this is the first report revealing that the evacuation was associated with the risk of polycythemia. This information could be very important for periodic health checkup and lifestyle recommendations for evacuees in the future.
    BMC Public Health 12/2014; 14:1318. · 2.32 Impact Factor
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    ABSTRACT: Background: Lymphocytes are susceptible to damage from radiation, and the white blood cell (WBC) count, including counts of neutrophils and lymphocytes, is a useful method of dosimetry. According to the basic survey of the Fukushima Health Management Survey (FHMS), among 13 localities where evacuation was recommended, Iitate and Namie had more individuals with external radiation exposure of more than 5 mSv than the other evacuation areas. We analyzed whether or not WBC, neutrophil, and lymphocyte counts decreased after the disaster.Methods: The subjects of this study were 45 278 men and women aged 20 to 99 years (18 953 men and 26 325 women; mean age 56 years) in the evacuation zone who participated in the Comprehensive Health Check (CHC) from June 2011 to the end of March 2012.Results: Significant differences were detected in the mean values of WBC, neutrophil, and lymphocyte counts, and for the proportion of individuals under the minimum standard for WBC and neutrophil counts, among the 13 localities. However, the distribution of individuals at each 200-cell/µL increment in lymphocyte count were similar in these areas, and the WBC, neutrophil, and lymphocyte counts did not decrease in Iitate or Namie specifically.Conclusions: No marked effects of radiation exposure on the distribution of WBC counts, including neutrophil and lymphocyte counts were detected within one year after the disaster in the evacuation zone.
    Journal of epidemiology / Japan Epidemiological Association. 10/2014;
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    ABSTRACT: Idiopathic hyperammonemia (IHA) has been described as a complication of intensive chemotherapy for the treatment of hematologic malignancy but has subsequently been found in patients undergoing bone marrow transplantation and in those with solid tumors treated with 5-fluorouracil. Although IHA is a rare complication, it is sometimes associated with high mortality in hematologic malignancies. Here we report the case of a 15-year-old boy in whom hyperammonemia developed during the initial treatment with prednisolone for newly diagnosed acute lymphoblastic leukemia and who survived after early detection and oral lactulose therapy. To the best of our knowledge, this is the first report of IHA that was not induced by intensive chemotherapy, stem cell transplantation, or asparaginase therapy in a patient with newly diagnosed leukemia, but developed during an initial treatment with a steroid. Early detection of IHA by measuring the plasma ammonia level in patients with neurological symptoms may improve the outcome.
    Journal of Pediatric Hematology/Oncology 09/2014; · 0.96 Impact Factor
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    ABSTRACT: Background Despite improvements in first-line therapies, the outcomes of relapsed or refractory childhood acute leukaemia that has not achieved complete remission after relapse, has relapsed after stem cell transplantation (SCT), has primary induction failure and has relapsed with a very unfavourable cytogenetic risk profile, are dismal.Objectives and Methods We evaluated the feasibility and efficacy of T-cell-replete haploidentical peripheral blood stem cell transplantation (haplo-SCT) with low-dose anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate and prednisolone (PSL) in 14 paediatric patients with high-risk childhood acute leukaemia.ResultsAll patients achieved complete engraftment. The median time to reaching an absolute neutrophil count of more than 0.5 × 109 L−1 was 14 days. Acute graft-vs-host disease (aGVHD) of grades II–IV and III–IV developed in 10 (71%) and 2 (14%) patients, respectively. Treatment-related mortality and relapse occurred in one (7%) patient and six (43%) patients, respectively. Eleven patients were alive and seven of them were disease-free with a median follow-up of 36 months (range: 30–159 months). The probability of event-free survival after 2 years was 50%.Conclusion These findings indicate that T-cell-replete haplo-SCT, with low-dose ATG and PSL, provides sustained remission with an acceptable risk of GVHD in paediatric patients with advanced haematologic malignancies.
    Transfusion Medicine 09/2014; · 1.26 Impact Factor
  • Kei Ogasawara, Yoshinobu Honda, Mitsuaki Hosoya
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    ABSTRACT: Cerebro-costo-mandibular syndrome (CCMS) is a rare disorder characterized by multiple rib abnormalities, micrognathia described as Pierre–Robin sequence, and cerebral involvement. Appropriate management of respiratory distress immediately after birth is crucial to rescue these patients. A boy, having a mother with Pierre–Robin sequence and a sister with CCMS, was diagnosed prenatally with CCMS and successfully treated with ex utero intrapartum treatment (EXIT) at 36 weeks 6 days of gestation. EXIT would be an effective option for rescuing patients with prenatally diagnosed CCMS and preventing neonatal hypoxia.
    Pediatrics International 08/2014; 56(4). · 0.73 Impact Factor
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    ABSTRACT: Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass without frank abscess formation. We report a case of acute focal bacterial nephritis without pyuria in a five-month-old boy presenting with high urinary β2-microglobulin (β2-MG) and N-Acetyl-β-(D)-Glucosaminidase (NAG) levels. The infant initially presented with high-grade fever, and plain computed tomography (CT) showed a nearly isodense mass, and contrast-enhanced abdominal CT showed a wedge-shaped hypodense lesion. Enterococcus was detected in the subsequent urine culture. A diagnosis of AFBN was made on the basis of his high inflammatory reaction, contrast-enhanced abdominal CT findings and high urinary β2-MG and NAG levels. He was treated with Ceftriaxone and subsequent improvement in inflammatory reaction and contrast-enhanced CT findings were observed. Voiding cystourethrogram (VCUG) showed a grade V right VUR. This case suggests that urinary β2-MG and NAG levels may be useful additional markers for the diagnosis of AFBN without pyuria.
    Fukushima journal of medical science 07/2014;
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    ABSTRACT: Malignant peritoneal mesothelioma in children is a very rare disease and has a poor prognosis. Unlike malignant mesothelioma in adults, there is no clear causal association between this very rare malignancy in children and asbestos exposure. We report a case of peritoneal mesothelioma in an 11-year-old boy who presented with ascites. He was diagnosed with malignant mesothelioma on the basis of histopathological findings. His disease showed resistance to pemetrexed, but was treated successfully with platinum-based therapy with gemcitabine. He has achieved long-term survival in partial remission with stable disease.
    Anti-cancer drugs. 07/2014;
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    ABSTRACT: AimSome patients with severe IgA nephropathy (IgAN) are resistant to multi-drug combination therapy; however, there have been few reports on the risk factors for non-responsiveness to treatment for severe IgAN. We, therefore, evaluated the risk factors for non-responsiveness to treatment in cases of severe IgAN.Methods We collected data on 44 children who had been diagnosed with IgAN with diffuse mesangial proliferation and treated with multi-drug combination therapy. The children were divided into two groups based on the prognosis at the latest follow-up. Group 1 consisted of 30 children with normal urine and 9 children with minor urinary abnormalities and Group 2 consisted of 4 children with persistent nephropathy and one child with renal insufficiency. The clinical, laboratory, and pathological findings for both groups were analyzed.ResultsThe age at the onset in Group 2 was higher than that in Group1. C3 deposits and high chronicity index values at the first renal biopsy were more frequently found in Group 2 than in Group 1 patients. IgA deposits, serum IgA and MRP 8/14 levels, and glomerular and interstitial MRP8+CD68+ scores at the second biopsy were all higher in Group 2 than in Group 1 patients.Conclusions Our results, although based on only a small number of patients in a retrospective study, suggest that age, presence of C3 deposits and interstitial changes at the onset, and persistent renal inflammatory activation may be risk factors for non-responsiveness to treatment for IgAN with diffuse mesangial proliferation.
    Nephrology 03/2014; · 1.86 Impact Factor
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    ABSTRACT: Most wheezing episodes in infants are caused and exacerbated by virus-induced lower respiratory tract infections. However, there are few reports of epidemiologic and clinical virus-specific research with a focus on virus-induced wheezing. The purpose of the current study was to characterize the clinical presentation of virus-induced wheezing in pediatric patients <3 years of age who were hospitalized with lower respiratory tract infections. Of the 412 patients in the study, 216 were followed for 3 years. Nasopharyngeal aspirates collected from the patients at the time of admission were examined for the presence of respiratory syncytial virus (RSV), rhinovirus (RV), parainfluenza-3 virus (PIV-3), human metapneumovirus (hMPV), and influenza virus (Flu) using reverse-transcription polymerase chain reaction and rapid diagnostic tests. Clinical signs were assessed using a severity scoring system. In patients with wheezing at the time of admission, RSV, RV, RSV+RV, Flu, PIV-3, and hMPV were detected in 33, 14, 8, 8, 5, and 3 % of samples, respectively. There were no differences in age and severity scores between patients harboring more prevalent viruses (RSV and RV) and those with less common infections. Patients with wheezing and RV-positive aspirates at the time of admission were more likely to develop subsequent wheezing during the following 3 years. Conclusion: RSV and RV infections are factors in the development and exacerbation of wheezing after virus-induced lower respiratory tract infections. Moreover, RV-induced wheezing may be associated with subsequent recurrent wheezing and the development of asthma.
    European Journal of Pediatrics 02/2014; · 1.98 Impact Factor
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    ABSTRACT: The incidence of obesity-related glomerulopathy (ORG) has increased over the last decade, but there have been few reports on ORG in Japanese children. Reported herein are two children with ORG identified on school urinary screening (SUS). Patient 1 was a 12-year-old boy in whom proteinuria was first detected on SUS. His body mass index (BMI) was 33.8 kg/m(2) and he had hypertension and hyperuricemia. Patient 2, a 10-year-old boy, also had proteinuria identified on SUS. His BMI was 34.8 kg/m(2) , and he had fatty liver, hyperuricemia, and hypercholesterolemia. Both were diagnosed with ORG based on obesity, proteinuria, and renal pathological findings. After treatment, including candesartan, food restriction and physical exercise, urinary protein excretion was decreased in both cases. We believe that such school urinary screening programs may be effective for the early identification and treatment of children with ORG.
    Pediatrics International 02/2014; 56(1):115-8. · 0.73 Impact Factor
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    ABSTRACT: Background There have been a number of reports on large outbreaks of hemolytic uremic syndrome (HUS), but there have been no long-term studies of sporadic HUS in Japan. This study therefore investigated the epidemiology and prognosis of HUS in Fukushima Prefecture over a 26 year period. Methods The medical records of 26 patients with HUS between 1987 and 2012 were collected. These children were divided into two groups: those with HUS following an episode of gastroenteritis, often with bloody diarrhea (D + HUS; n = 24) and those with HUS not associated with prodromal diarrhea (D–HUS; n = 2). The D + HUS group was further subdivided into group A (11 patients requiring dialysis) and group B (13 patients not requiring dialysis). The epidemiological and clinical data, as well as prognosis, were retrospectively investigated for each group. ResultsApproximately 90% of HUS patients belonged to the D + HUS group. In this group, the mean number of patients per year from 1987 to 1999, and from 2000 to 2012 was 0.92 ± 0.95, and 1.08 ± 0.86, respectively. On admission, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine and serum fibrinogen degradation product (FDP) levels in group A were all higher than in group B. Serum albumin level and estimated glomerular filtration rate (eGFR) in group A were lower than in group B. At 6 months after the onset of HUS in the D + HUS group, renal function was normal. Conclusions The frequency of HUS was constant from 1987 to 2012 in Fukushima. and serum LDH, ALT, BUN, creatinine, and FDP levels as well as eGFR might be risk factors for dialysis in D + HUS children.
    Pediatrics International 02/2014; 56(1). · 0.73 Impact Factor
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    ABSTRACT: Myeloid/natural killer cell precursor acute leukemia (MNKL) is an aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (SCT). We report a patient with MNKL who had a donor lymphocyte infusion (DLI) for relapse after T cell-replete human leukocyte antigen (HLA)-haploidentical SCT, but relapsed again 20 months later with loss of mismatched HLA. This case suggests that a strong graft-versus-leukemia effect of haploidentical SCT can be expected in MNKL patients. In the haploidentical setting, DLI should be considered for patients with relapsed leukemia whose leukemic cells have not lost HLA cell surface expression. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 01/2014; · 2.35 Impact Factor
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    ABSTRACT: The objective of this study was to estimate the efficacy of the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir for decreasing viral load and to investigate whether NAI treatment decreases viral susceptibility to NAIs over time in children with influenza B virus infection. Of 27 patients with influenza B virus infection, 8 and 9 were treated with oseltamivir and zanamivir, respectively, whereas 10 received no NAI. Nasal aspiration samples, collected every morning until negative antigen results in two consecutive samples were observed, were subjected to viral load measurements by quantitative real-time reverse transcription-polymerase chain reaction and viral susceptibility to NAI by NA inhibition assays. Viral load decreased in both the oseltamivir and zanamivir groups by day 2 but increased in the no-NAI treatment group. Viral load in the oseltamivir and zanamivir groups on day 5 was 2.6% and 9.2% of that on day 0, respectively, whereas it was 26.4% in the no-NAI treatment group. Mean 50% inhibitory concentration (IC50) values of oseltamivir and zanamivir in the no-NAI treatment group were 5.0-6.6 and 1.3-1.8 nM, respectively. Mean IC50 values of oseltamivir and zanamivir in patients treated with oseltamivir and zanamivir were 3.9-8.8 and 1.3-1.8 nM, respectively. No major decrease in viral susceptibility to NAIs was observed during or after NAI treatment. NAI treatment was effective for inhibiting viral replication during the early days of illness and did not decrease viral susceptibility to NAIs in patients with influenza B virus infection.
    The Pediatric Infectious Disease Journal 01/2014; · 3.14 Impact Factor
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    ABSTRACT: Group B Streptococcus (GBS) is one of the leading causes of neonatal bacterial infections. Population-based surveillance of GBS-related invasive diseases among newborns and infants from 10 prefectures in Japan was performed between 2007 and 2012. The characteristics of cases and isolated GBS are described in this study. The incidence rate of GBS-related invasive diseases was 0.13 per 1,000 live births. Analysis of GBS samples obtained from 60 invasive cases showed that the most frequent serotypes were III (48.3%), Ia (30.0%), and Ib (10.0%). All isolates were susceptible to penicillin G, ampicillin, cefotaxime, imipenem, and panipenem. However, 14, 2, and 7 isolates were resistant to erythromycin, clindamycin, and both erythromycin and clindamycin, respectively. Multilocus sequence typing revealed that GBS sequence type (ST) 23, ST17, and ST335 caused higher incidences of meningitis. These data show that serotypes III, Ia, and Ib together caused more than 80% of invasive infections in Japanese infants, and that GBS strains are still susceptible to β-lactam antibiotics.
    Japanese journal of infectious diseases. 01/2014; 67(5):356-60.
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    ABSTRACT: Recombinant human soluble thrombomodulin (rhTM) is a promising therapeutic natural anticoagulant and is used clinically for the treatment of disseminated intravascular coagulation (DIC). Herein is reported the cases of two HUS children treated with rhTM. The patients were diagnosed as having typical HUS on the basis of thrombocytopenia, hemolytic anemia, acute renal failure, and the detection Escherichia coli 0157. I.v. rhTM was started as an anti-coagulant drug. At 2 days after the first treatment in both patients, fibrin/fibrinogen degradation products and d-dimer levels were significantly decreased, and there was a subsequent slight improvement in thrombocytopenia, and a decrease in serum lactate dehydrogenase level. Urinary protein excretion gradually diminished and a decrease in serum creatinine level was observed. The patients did not require dialysis therapy. The present results suggest that rhTM may be a safe and effective treatment for DIC complicated with HUS in children.
    Pediatrics International 10/2013; 55(5):e139-42. · 0.73 Impact Factor
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    ABSTRACT: Hyperammonemia of newborns should be treated promptly, and the outcome depends on the rapid elimination of excessive plasma ammonia. We encountered a case of transient hyperammonemia in an extremely low-birthweight infant whose plasma ammonia decreased sufficiently after continuous hemodialysis therapy. It seems that continuous hemodialysis therapy using the peripheral artery and umbilical vein is useful for hyperammonemia of extremely low-birthweight infants; however, there are several problems to consider due to the immaturity of these infants.
    Pediatrics International 10/2013; 55(5):656-8. · 0.73 Impact Factor
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    ABSTRACT: Reported herein is a case of relapse of nephrotic syndrome (NS) after intravitreal injection of bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), in a 16-year-old girl. She had a diagnosis of steroid-dependent NS and had been treated with prednisolone, and remained in remission. The patient had had visus brevior 10 years previously, and was diagnosed with severe myopic choroidal neovascularization (mCNV). Intravitreal bevacizumab was given for mCNV. At 9 days after intravitreal injection of bevacizumab, proteinuria was positive. The patient had relapse of NS caused by bevacizumab, and steroid pulse therapy was then given and the proteinuria resolved. It is necessary to take particular care to prevent NS relapses in patients with mCNV treated with intravitreal bevacizumab.
    Pediatrics International 06/2013; 55(3):e46-8. · 0.73 Impact Factor
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    ABSTRACT: Here we report the case of a 9-year-old boy with acute respiratory distress syndrome (ARDS) caused by novel H1N1 swine-origin influenza virus A. A diagnosis of ARDS caused by a novel influenza A (H1N1) virus was made on the basis of chest X-ray and computed tomography together with low oxygenation index (OI) and the detection of novel influenza A (H1N1) virus from tracheal secretion samples. Oseltamivir phosphate and prone positioning were effective in the treatment of ARDS in this case. These findings suggest that anti-viral drugs and prone positioning can play an important role in the improvement of ARDS caused by novel H1N1 swine-origin influenza virus A.
    Pediatrics International 06/2013; 55(3):e77-80. · 0.73 Impact Factor

Publication Stats

1k Citations
279.42 Total Impact Points


  • 1998–2014
    • Fukushima Medical University
      • • Department of Pediatrics
      • • Division of Medicine
      Hukusima, Fukushima, Japan
  • 2011
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
  • 1993
    • Tokushima Bunri University
      • Faculty of Pharmaceutical Sciences
      Tokushima-shi, Tokushima-ken, Japan
  • 1992
    • KU Leuven
      • Department of Biomedical Kinesiology
      Leuven, VLG, Belgium