Faculty Profiles - OTSUKA Fumio

Long-term observation of osteomalacia caused by adefovir-induced Fanconi's syndrome. Reviewed

Tomohiro Terasaka, Eijiro Ueta, Hirotaka Ebara, Koichi Waseda, Yoshihisa Hanayama, Akinobu Takaki, Tomoko Kawabata, Hitoshi Sugiyama, Ko Hidani, Fumio Otsuka

Acta medica Okayama 68 ( 1 ) 53 - 6 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

A 64-year-old man suffering polyarthralgia and bone pain was referred to our hospital. Renal dysfunction, hypophosphatemia and increased levels of bone alkaline phosphatase were found. The patient's serum creatinine level had gradually increased after the initiation of adefovir dipivoxil administration for hepatitis B. In agreement with multifocal uptakes of bone scintigraphy, iliac bone biopsy revealed an abnormal increase in osteoid tissues. Reducing the dose of adefovir and initiating the administration of eldecalcitol were effective for reducing proteinuria and glucosuria, and for ameliorating bone pain with an increase in serum phosphate level. This case first showed a clinical course of hypophosphatemic osteomalacia caused by secondary Fanconi's syndrome for 8 years after adefovir administration. Early diagnosis is important for the reversibility of bone damage and for a better renal prognosis.

DOI： 10.18926/AMO/52145

Ceftriaxone-induced Biliary Sludge in a Patient with Uncontrolled Diabetes

Postpartum Breast Abscess Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus in Japan

Hideharu Hagiya, Sumiko Shiota, Wakana Sugiyama, Fumio Otsuka

BREASTFEEDING MEDICINE 9 ( 1 ) 45 - 46 2014.1

Lower Limb Infection in an Infant with Haemophilus influenzae Serotype b

Hideharu Hagiya, Fumio Otsuka

General Medicine 15 ( 1 ) 56 - 58 2014

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Fumio Otsuka

Internal Medicine 53 ( 21 ) 2549 - 2550 2014

Calcium Oxalate Crystals in the Lungs

Hideharu Hagiya, Soichiro Fushimi, Junya Itakura, Fumio Otsuka

Internal Medicine 53 ( 17 ) 2025 - 2026 2014

Acute generalized exanthematous pustulosis caused by daptomycin in a critically ill burn victim.

Hideharu Hagiya, Maya Kimura, Toru Miyamoto, Yuto Haruki, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 5 ) 511 - 4 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Acute generalized exanthematous pustulosis (AGEP) is a self-limiting type of drug eruption that frequently occurs as a reaction to antibiotics, particularly penicillins or macrolides. Daptomycin (DAP) is a newly developed antibiotic that specifically targets methicillin-resistant Staphylococcus aureus infection. We herein present the case of a 77-year-old severe burn victim who was diagnosed with DAP-induced AGEP while receiving treatment in an intensive care unit. Although rare, physicians should be aware that the administration of DAP can cause AGEP, which may complicate the clinical course of patients with a high fever and inflammation.

DOI： 10.2169/internalmedicine.53.0679

Fosfomycin for the treatment of prostate infection. Reviewed

Hideharu Hagiya, Megumi Ninagawa, Kou Hasegawa, Tomohiro Terasaka, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Toshiaki Sendo, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 22 ) 2643 - 6 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

A 69-year-old man with diabetes mellitus was diagnosed with a prostate abscess. Although the pathogen was fluoroquinolone-resistant Escherichia coli and the oral administration of trimethoprim-sulfamethoxazole was initiated, the infection recurred after three months. The antibiotic therapy was subsequently changed to intravenous fosfomycin, and the patient's condition promptly improved. Four weeks of fosfomycin therapy was successfully continued without any adverse events. In the era of antibiotic resistance, revival of forgotten drugs is an important issue for clinicians. Fosfomycin can be applied as an alternative option for prostate infections, considering the remaining susceptibility of multidrug-resistant pathogens to fosfomycin and the good pharmacokinetics of this drug in prostatic tissue.

DOI： 10.2169/internalmedicine.53.3098

Filarial chyluria as a rare cause of urinary retention. Reviewed

Hideharu Hagiya, Tomohiro Terasaka, Kosuke Kimura, Asuka Satou, Kikuko Asano, Koichi Waseda, Yoshihisa Hanayama, Takahide Takahashi, Michinori Aoe, Koji Iio, Toshiyuki Watanabe, Eisei Kondo, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 17 ) 2001 - 5 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

We herein describe a case of Wuchereria bancrofti infection in a previously healthy 37-year-old Nepalese man. The patient presented with a history of milky urine with subsequent acute urinary retention lasting for a few days. The presence of microfilariae was confirmed on both peripheral blood and urine smears obtained at midnight. He was conservatively treated with diethylcarbamazine combined with doxycycline. Filariasis was previously endemic in southern parts of Japan, although it has been eradicated. Clinicians should remember filariasis as a potential etiology of urinary retention, especially in cases that may be associated with imported infectious disease.

DOI： 10.2169/internalmedicine.53.2572

Recurrent Stenotrophomonas maltophilia bacteremia after iliac crest bone graft harvest. Reviewed

Hideharu Hagiya, Hiroko Ogawa, Tomoharu Ishida, Tomohiro Terasaka, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Masahiro Horita, Yasunori Shimamura, Eisei Kondo, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 15 ) 1693 - 8 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

We describe a rare case of recurrent Stenotrophomonas maltophilia bacteremia in a previously healthy 45-year-old man. The infection was caused by osteomyelitis at the site of an iliac crest bone graft harvest. A genetic analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed that the blood isolates and pathogens obtained from the surgical wound were identical. Initial treatment with levofloxacin and cefozopran was ineffective, but the patient's infection was successfully treated by long-term administration of latamoxef and trimethoprim-sulfamethoxazole. The present case suggests that attention should be given to the possibility of S. maltophilia infection in any situations.

DOI： 10.2169/internalmedicine.53.1995

Successful treatment of persistent MRSA bacteremia using high-dose daptomycin combined with rifampicin. Reviewed

Hideharu Hagiya, Tomohiro Terasaka, Kosuke Kimura, Asuka Satou, Kikuko Asano, Koichi Waseda, Yoshihisa Hanayama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 18 ) 2159 - 63 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

We herein report a case of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that was successfully treated with combination therapy consisting of high-dose daptomycin (DAP, 10 mg/kg) and rifampicin. The patient's condition was complicated with multiple infectious foci, including an iliopsoas abscess and epidural abscess, as well as discitis and spondylitis at the cervical, thoracic and lumbar levels. Monotherapy treatments with vancomycin, linezolid and usual-dose DAP were all ineffective. It has been shown that usual-dose DAP administration may result in the emergence of a resistant strain and treatment failure. We would like to emphasize the importance of high-dose DAP therapy for MRSA bacteremia, a condition with a potentially high mortality rate.

DOI： 10.2169/internalmedicine.53.2711

Actinomyces meyeri meningitis: the need for anaerobic cerebrospinal fluid cultures. Reviewed

Hideharu Hagiya, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 1 ) 67 - 71 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

We herein present a rare case of Actinomyces meyeri-induced meningitis that occurred in a patient of advanced age with poor oral hygiene. Although Gram staining of the cerebrospinal fluid (CSF) revealed Grampositive rods and a blood culture was positive for the organism, a bacterial culture of the CSF was negative. Anaerobic cultures of CSF specimens are not routinely performed; however, anaerobes are sometimes involved in central nervous system infection. We therefore believe that anaerobic cultures should be considered in high-risk cases, such as those involving necrotizing bowel lesions or poor oral hygiene. A negative result on a CSF culture can result in misdiagnosis and inappropriate treatment.

DOI： 10.2169/internalmedicine.53.0403

Epiglottic aphthous ulcers.

Hideharu Hagiya, Hiroyuki Hanakawa, Takayuki Katsuyama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 15 ) 1731 - 1731 2014

A case of vascular graft infection caused by Staphylococcus lugdunensis after femoropopliteal bypass operation.

Hideharu Hagiya, Mitsuaki Matsumoto, Takahiko Yamasawa, Yuto Haruki, Fumio Otsuka

Acta medica Okayama 68 ( 3 ) 171 - 5 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

A 79-year-old man who had undergone a right femoropopliteal (FP) bypass operation 6 weeks previously was diagnosed with vascular graft infection caused by Staphylococcus lugdunensis. Another FP bypass operation was performed, with long-term administration of antibiotics, and the patient eventually recovered well without any recurrences for over 2 years. Although S. lugdunens is classified as coagulase-negative Staphylococcus, its pathogenicity has been reported to be equal to that of S. aureus. Based on the literature review, the organism characteristically colonizes the inguinal area of human skin;thus, operations such as FP bypass grafting may place patients at a relatively high risk for infection by S. lugdunensis, a potentially high-pathogenicity organism.

Triangle sign on neck MRI.

Kosuke Kimura, Hideharu Hagiya, Yoshihisa Hanayama, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 9 ) 1035 - 6 2014

Effects of antibiotics administration on the incidence of wound infection in percutaneous dilatational tracheostomy. Reviewed

Hideharu Hagiya, Hiromichi Naito, Shingo Hagioka, Shuji Okahara, Naoki Morimoto, Nobuchika Kusano, Fumio Otsuka

Acta medica Okayama 68 ( 2 ) 57 - 62 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The effect of antibiotics during the perioperative period of percutaneous dilatational tracheostomy (PDT) is still controversial. A total of 297 patients who underwent the PDT procedure were divided into 2 groups:those administered antibiotics perioperatively and those not administered antibiotics. Wound infections were noted in 7 cases (incidence rate, 2.36%) and no death was recorded. Of the 69 patients without antibiotics, 5 developed wound infections (incidence rate, 7.25%), while only 2 of the 228 patients with antibiotics developed wound infections (incidence rate, 0.88%) (p＝0.002;risk ratio, 8.82;95% confidence interval, 1.67-46.6). Of the 7 cases of wound infection, 5 cases occurred during the early period after PDT (within 7 days). Collectively, the present results suggest that prophylactic administration of antibiotics may prevent the incidence of PDT-induced wound infection, especially in the early phase after the PDT procedures. The need for antibiotics in PDT should be reconsidered.

Comprehensive analysis of systemically disseminated ST8/non-USA300 type community-acquired methicillin-resistant Staphylococcus aureus infection.

Hideharu Hagiya, Junzo Hisatsune, Taro Kojima, Sumiko Shiota, Hiromichi Naito, Shingo Hagioka, Naoki Morimoto, Fumio Otsuka, Motoyuki Sugai

Internal medicine (Tokyo, Japan) 53 ( 8 ) 907 - 12 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is genetically heterogeneous and various genotypes are spreading worldwide. We herein report a case of systematically disseminated Japan-intrinsic CA-MRSA infection that was successfully treated. A genetically identical single strain was isolated from a total of 11 different parts of the patient's body, and the pathogen was found to be multilocus sequence type 8, staphylococcal cassette chromosome mec IV, coagulase type III and negative for both Panton-Valentine leukocidin and arginine catabolic mobile element. The epidemiology and pathogenicity of the Japan-intrinsic CA-MRSA strain remain unknown, and further investigation of this life-threatening organism is warranted.

DOI： 10.2169/internalmedicine.53.1746

Rhombencephalitis caused by Listeria monocytogenes.

Hideharu Hagiya, Fumio Otsuka

Internal medicine (Tokyo, Japan) 53 ( 6 ) 639 - 40 2014

Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study. Reviewed International journal

Toshio Naito, Masafumi Mizooka, Fujiko Mitsumoto, Kenji Kanazawa, Keito Torikai, Shiro Ohno, Hiroyuki Morita, Akira Ukimura, Nobuhiko Mishima, Fumio Otsuka, Yoshio Ohyama, Noriko Nara, Kazunari Murakami, Kouichi Mashiba, Kenichiro Akazawa, Koji Yamamoto, Shoichi Senda, Masashi Yamanouchi, Susumu Tazuma, Jun Hayashi

BMJ open 3 ( 12 ) e003971 - e003971 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：BMJ PUBLISHING GROUP

OBJECTIVE: Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. DESIGN: A nationwide retrospective study. SETTING: 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. PARTICIPANTS: This study included patients ≥18 years diagnosed with 'classical fever of unknown origin' (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. RESULTS: A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19-94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. CONCLUSIONS: With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

DOI： 10.1136/bmjopen-2013-003971

Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells. Reviewed International journal

Tomohiro Terasaka, Fumio Otsuka, Naoko Tsukamoto, Eri Nakamura, Kenichi Inagaki, Kishio Toma, Kanako Ogura-Ochi, Christine Glidewell-Kenney, Mark A Lawson, Hirofumi Makino

Molecular and cellular endocrinology 381 ( 1-2 ) 8 - 15 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentration-dependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ERα and ERβ, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells.

DOI： 10.1016/j.mce.2013.07.009