Faculty Profiles - OTSUKA Fumio

Actinomyces turicensis Bacteremia Secondary to Pyometra. Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Kosuke Kimura, Kan Hasegawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 21 ) 2775 - 7 2015

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

We herein present a rare case of Actinomyces turicensis bacteremia that was caused by pyometra. The patient was successfully treated with transvaginal drainage and antibiotic therapy. A literature review in MEDLINE showed that there have been only 8 previously reported cases of A. turicensis bacteremia. This infection frequently occurs in patients with visceral abscesses, and blood culture examinations usually reveal a polymicrobial pattern. However, the prognosis of such patients has been reported to generally be benign. Due to difficulties in performing bacterial identification and the wide-spectrum clinical pictures associated with this bacteremia, no comprehensive understanding of the clinical features of each Actinomyces species has yet been established.

DOI： 10.2169/internalmedicine.54.4637

Neurosyphilis Is a Long-forgotten Disease but Still a Possible Etiology for Dementia. Reviewed

Hideharu Hagiya, Kentaro Deguchi, Kiyohiro Kawada, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 21 ) 2769 - 73 2015

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

We herein report a heterosexual Japanese man in his forties who had been suffering from advanced dementia and personality change for 4 years. Positive results of a serological test for syphilis, Treponema pallidum hemagglutination assay, and fluorescent treponemal antibody-absorption test of both serum and cerebral spinal fluid led to the diagnosis of neurosyphilis. Jarisch-Herxheimer reaction was seen shortly after the first dose of penicillin was administered to the patient. His cognitive function did not recover after treatment. The incidence of syphilis has been reported to be increasing. Neurosyphilis should not be overlooked as an etiology for progressive dementia even in this post-antibiotic era.

DOI： 10.2169/internalmedicine.54.4956

Cytomegalovirus as an Insidious Pathogen Causing Duodenitis. Reviewed

Hideharu Hagiya, Masaya Iwamuro, Takehiro Tanaka, Yoshihisa Hanayama, Fumio Otsuka

Acta medica Okayama 69 ( 5 ) 319 - 23 2015

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

A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion;however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features.

Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study. Reviewed

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

Internal medicine (Tokyo, Japan) 54 ( 16 ) 1989 - 94 2015

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

OBJECTIVE: Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. METHODS: A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. PATIENTS: This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. RESULTS: The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. CONCLUSION: The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

DOI： 10.2169/internalmedicine.54.3313

Tetanus in a 19-year-old Japanese Woman. Reviewed

Hideharu Hagiya, Takahiro Hirayama, Toyomu Ugawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 14 ) 1825 - 1825 2015

Relapsing Polychondritis Followed Up with FDG-PET. Reviewed

Hideharu Hagiya, Koichi Waseda, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 13 ) 1675 - 6 2015

Eagle's Syndrome Manifesting as Chronic Swallowing Pain. Reviewed

Hideharu Hagiya, Koichi Waseda, Hiroko Ogawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 54 ( 10 ) 1321 - 1321 2015

CT visualising infective vegetation. International journal

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Fumio Otsuka

BMJ case reports 2014 2014.12

Gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection: a case report. Reviewed International journal

Kazuhiro Omori, Yoshihisa Hanayama, Koji Naruishi, Kentaro Akiyama, Hiroshi Maeda, Fumio Otsuka, Shogo Takashiba

Clinical case reports 2 ( 6 ) 286 - 95 2014.12

Language：English Publishing type：Research paper (scientific journal)

It has been suggested that vitamin C deficiency/scurvy is associated with gingival inflammatory changes; however, the disorder is very infrequently encountered in the modern era. Here, we report a case of extensive gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection.

DOI： 10.1002/ccr3.114

Aortic vascular graft infection caused by Cardiobacterium valvarum: a case report. Reviewed International journal

Hideharu Hagiya, Susumu Kokeguchi, Hiroko Ogawa, Tomohiro Terasaka, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Kaori Oda, Hisatoshi Mori, Toru Miyoshi, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 20 ( 12 ) 804 - 9 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

A 53-year-old man with a past medical history of total arch replacement surgery and severe aortic regurgitation presented with a 1-month history of persistent general malaise, anorexia, body weight loss and night sweats. His recent history included gingival hyperplasia for 6 years, gingivitis after tooth extraction 3 years before, prolonged inflammatory status for 4 months, fundal hemorrhage and leg tenderness for 2 months. A pathogen was detected from blood culture, but conventional microbiological examination failed to identify the pathogen. The organism was eventually identified as Cardiobacterium valvarum by 16S rRNA analysis, and the patient was diagnosed with infective endocarditis and prosthetic vascular graft infection. The patient received intravenous antibiotic therapy using a combination of ceftriaxone and levofloxacin for 5 weeks and was discharged with a good clinical course.
C. valvarum is a rare human pathogen in clinical settings. Only 10 cases have been reported to date worldwide, and therefore, the clinical characteristics of C. valvarum infection are not fully known. This is a first well-described case of C. valvarum infection in Japan, and further, a first report of aortic prosthetic vascular graft infection worldwide. Identification of C. valvarum is usually difficult due to its phenotypic characteristics, and molecular approaches would be required for both clinicians and microbiologists to facilitate more reliable diagnosis and uncover its clinical picture more clearly. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2014.07.008

Pantoea dispersa bacteremia caused by central line-associated bloodstream infection

Hideharu Hagiya, Fumio Otsuka

BRAZILIAN JOURNAL OF INFECTIOUS DISEASES 18 ( 6 ) 696 - 697 2014.11

Mycotic abdominal aortic aneurysm caused by Campylobacter fetus: a case report and literature review. International journal

Hideharu Hagiya, Mitsuaki Matsumoto, Hiroshi Furukawa, Tomoko Murase, Fumio Otsuka

Annals of vascular surgery 28 ( 8 ) 1933.e7-1933.e14 2014.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Campylobacter spp. usually cause gastrointestinal infections, but among them, Campylobacter fetus is a well-known organism causing mycotic abdominal aortic aneurysm (MAAA), which requires proper surgical intervention and antibiotic therapy. We report a 65-year-old man who was successfully treated by an in situ operation using a rifampicin (RFP)-bonded J-Graft for C. fetus-induced MAAA. We performed a review of the English literature on MAAA caused by C. fetus and summarized the results of the cases (28 cases). All but 2 of the patients (92.9%) were men. Blood culture and arterial wall culture were positive in 63% and 73.1% of the cases, respectively. Aneurysm rupture was seen in half of the patients, and approximately half of those patients died. Among the 18 patients who underwent in situ graft replacement, only 1 patient (5.6%) died after surgery. Antibiotic therapy was performed for more than 1 month in most cases, and overall mortality rate was 25.9% (7 of 27 cases, 3 deaths before the operation and 4 deaths after surgery). Although extra-anatomic bypass has been conventionally performed after complete resection of an MAAA, the utility of in situ surgery has generally been recognized. Our review suggests that the in situ operation can be a choice also in cases of C. fetus-associated MAAA. Furthermore, our case suggested the clinical utility of a newly manufactured prosthetic graft, J-Graft, for such surgical treatment.

DOI： 10.1016/j.avsg.2014.06.072

Clinical utility of string test as a screening method for hypermucoviscosity-phenotype Klebsiella pneumoniae. Reviewed International journal

Hideharu Hagiya, Naoto Watanabe, Miyako Maki, Tomoko Murase, Fumio Otsuka

Acute medicine & surgery 1 ( 4 ) 245 - 246 2014.10

Emergence of third-generation cephalosporin-resistant Enterobacteriacae in a Japanese critical care setting. Reviewed International journal

Hideharu Hagiya, Tomoko Murase, Masato Suzuki, Fumio Otsuka, Keigo Shibayama

Acute medicine & surgery 1 ( 4 ) 256 - 258 2014.10

Language：English Publishing type：Research paper (scientific journal)

Aim: Extended-spectrum beta-lactamases and AmpC beta-lactamases give resistance to Enterobacteriaceae against cephalosporins, which are important drugs in various clinical settings. Within 5 days, a total of eight strains of Citrobacter freundii and two strains of Escherichia coli, all of which were resistant to third-generation cephalosporins, were isolated from six different patients in a critical care center. We carried out epidemiological and genetic studies to confirm the situation to be an outbreak by a single strain or a beta-lactamase-producing gene. Methods: A review of patients' clinical data, pulsed-field gel electrophoresis epidemiological study against the strains, and polymerase chain reaction analysis for the detection of extended-spectrum beta-lactamase genes (TEM, SHV, CTX-M-1, CTX-M-2, and CTX-M-9) and multiplex polymerase chain reaction analysis for plasmid-mediated AmpC-beta-lactamase genes were carried out. Results: Pulsed-field gel electrophoresis showed none of the subjects were genetically identical organisms. However, all strains possessed either extended-spectrum beta-lactamases (TEM, CTX-M-2, and CTX-M-9) or AmpC-beta-lactamases. One patient carried both extended-spectrum beta-lactamase- and AmpC- beta-lactamase-producing organisms. Conclusion: This study revealed that various types of easily transmittable drug resistance genes exist in the critical care setting concurrently. This case was not an outbreak of such strains, but the present situation might indicate a more serious condition than a mere outbreak of a single resistant strain. Enterobacteriaceae that possess extended-spectrum beta-lactamases or AmpC-beta-lactamases are increasingly common in many medical institutions in Japan, and constitutive monitoring of drug-resistant organisms and proper contact precautions are essential to prevent possible outbreaks.

DOI： 10.1002/ams2.64

Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells. Reviewed International journal

Eri Nakamura, Fumio Otsuka, Tomohiro Terasaka, Kenichi Inagaki, Takeshi Hosoya, Naoko Tsukamoto-Yamauchi, Kishio Toma, Hirofumi Makino

The Journal of steroid biochemistry and molecular biology 143 233 - 9 2014.9

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

The ovarian bone morphogenetic protein (BMP) system is a physiological inhibitor of luteinization in growing ovarian follicles. BMP-6, which is expressed in oocytes and granulosa cells of healthy follicles, specifically inhibits FSH actions by suppressing adenylate cyclase activity. In the present study, we studied the role of melatonin in ovarian steroidogenesis using rat primary granulosa cells of immature female rat ovaries by focusing on the interaction with BMP-6 activity. Treatment with melatonin had no direct effect on FSH-induced progesterone or estradiol production by granulosa cells, and the results were not affected by the presence of co-cultured oocytes. In addition, synthesis of cAMP by granulosa cells was not significantly altered by melatonin treatment. To elucidate the interaction between activities of melatonin and BMPs, the effect of melatonin treatment on suppression of progesterone synthesis by BMP-6 was investigated. Interestingly, the inhibitory effect of BMP-6 on FSH-induced progesterone production was impaired by co-treatment with melatonin. Granulosa cells express higher levels of MT1 than MT2, and BMP-6 had no significant effect on MT1 expression in granulosa cells. However, BMP-6-induced Smad1/5/8 phosphorylation and Id-1 transcription were suppressed by melatonin, suggesting that melatonin has an inhibitory effect on BMP receptor signaling in granulosa cells. Although the expression levels of ALK-2, -6, ActRII and BMPRII were not affected by melatonin, inhibitory Smad6, but not Smad7, expression was upregulated by melatonin. Thus, melatonin plays a role in the regulation of BMP-6 signal intensity for controlling progesterone production in the ovary. These findings suggest that the effect of melatonin on maintenance of ovarian function is, at least in part, due to the regulation of endogenous BMP activity in granulosa cells.

DOI： 10.1016/j.jsbmb.2014.04.003

Vasohibin-1 deficiency enhances renal fibrosis and inflammation after unilateral ureteral obstruction. Reviewed International journal

Hiroyuki Watatani, Yohei Maeshima, Norikazu Hinamoto, Hiroko Yamasaki, Haruyo Ujike, Katsuyuki Tanabe, Hitoshi Sugiyama, Fumio Otsuka, Yasufumi Sato, Hirofumi Makino

Physiological reports 2 ( 6 ) 2014.6

Language：English Publishing type：Research paper (scientific journal)

Tubulointerstitial injuries are known to predict the deterioration of renal function in chronic kidney disease (CKD). We recently reported the protective role of Vasohibin-1(VASH-1), a negative feedback regulator of angiogenesis, in diabetic nephropathy, but its impact on tubulointerstitial injuries remains to be elucidated. In the present study, we evaluated the role of endogenous VASH-1 in regulating the tubulointerstitial alterations induced by unilateral ureteral obstruction (UUO), and assessed its role on fibrogenesis and the activation of Smad3 signaling in renal fibroblasts. UUO was induced in female Vasohibin-1 heterozygous knockout mice (VASH-1(+/-)) or wild-type (WT) (VASH-1(+/+)) littermates. Mice were sacrificed on Day 7 after left ureter ligation, and the kidney tissue was obtained. Interstitial fibrosis, the accumulation of type I and type III collagen and monocytes/macrophages infiltration in the obstructed kidneys (OBK) were significantly exacerbated in VASH-1(+/-) mice compared with WT mice (Day 7). The increases in the renal levels of TGF-β1, pSmad3, NF-κB pp65, CCL2 mRNA, and the number of interstitial fibroblast-specific protein-1 (FSP-1)(+) fibroblasts in the OBK were significantly aggravated in VASH-1(+/-) mice. In addition, treatment with VASH-1 siRNA enhanced the TGF-β1-induced phosphorylation of Smad3, the transcriptional activation of the Smad3 pathway and the production of type I/type III collagen in fibroblasts, in vitro. Taken together, our findings demonstrate a protective role for endogenous VASH-1 on tubulointerstitial alterations via its regulation of inflammation and fibrosis and also show the direct anti-fibrotic effects of VASH-1 on renal fibroblasts through its modulation of TGF-β1 signaling.

DOI： 10.14814/phy2.12054

【市中感染型MRSAの動向と対処法】ST8/non-USA300株による全身播種性市中感染型MRSA感染症の1例

Retroperitoneal bronchogenic cyst: a rare incidentaloma discovered in a juvenile hypertensive patient. Reviewed International journal

Tomohiro Terasaka, Fumio Otsuka, Kanako Ogura-Ochi, Tomoko Miyoshi, Kenichi Inagaki, Yasuyuki Kobayashi, Yasutomo Nasu, Hirofumi Makino

Hypertension research : official journal of the Japanese Society of Hypertension 37 ( 6 ) 595 - 7 2014.6

萩谷英大, 久恒順三, 森本直樹, 大塚文男, 菅井基行

化学療法の領域 30 ( 5 ) 779 - 787 2014.4

Language：Japanese Publisher：(株)医薬ジャーナル社

市中感染型メチシリン耐性黄色ブドウ球菌(CA-MRSA)は重症感染症を引き起こす起炎菌として知られているが、遺伝子的に多様であり、さまざまなタイプが世界中に分布している。本症例は、multilocus sequence type 8、IV型SCCmec(staphylococcal cassette chromosome mec)、III型コアグラーゼ陽性、Panton-Valentine leukocidinおよびarginine catabolic mobile element陰性の単一株により発症した全身播種性の重症CA-MRSA感染症のまれな一例である。筋骨格系を中心に全身に感染巣を形成しており、遺伝学的に同一のCA-MRSAを患者の異なる11部位より検出した。わが国におけるCA-MRSAの疫学および病原性は未解明である部分が多いが、本症例でもCA-MRSAの高病原性が示唆された。今後さらなる解析が期待される。(著者抄録)

本態性高血圧の初期治療における第一選択薬決定のアルゴリズム作成と有用性の検討

萱野由佳, 三好智子, 水島孝明, 花山宜久, 黒田真生, 尾上洋, 相良英憲, 座間味義人, 大塚文男, 名倉弘哲

Progress in Medicine 34 ( 3 ) 527 - 536 2014.3

Language：Japanese Publisher：(株)ライフ・サイエンス

本態性高血圧症は本邦において極めて患者数の多い疾患であり、その治療は食事・運動療法に加えて薬物治療が重要である。『高血圧治療ガイドライン2009』では、本態性高血圧に対する5種類の第一選択薬であるカルシウム拮抗薬、アンジオテンシンII受容体拮抗薬、アンジオテンシン変換酵素阻害薬、β遮断薬、利尿薬が提示されている。本態性高血圧の初期治療での薬剤選択に際して医師が考慮すべき事項は極めて煩雑であり、医師の処方薬決定を困難にしている。本研究では、本態性高血圧初期治療における処方決定に役立つためのアルゴリズムの作成を試みた。さらに、調査対象となる総合内科医師と保険薬剤師にアルゴリズムを配付し、一定の試用期間後にアルゴリズムの使用感に関する有用性の評価を実施したところ、本アルゴリズムは総合内科医師、保険薬剤師それぞれから高い評価を得た。また、医師の処方決定時の思考をおおむね反映していることが検証できた。したがって、作成したアルゴリズムは医師の処方決定の理解の手助けとなる可能性が示唆された。加えて、本アルゴリズムは薬剤師が処方解析を行ううえでもその有用性は高いと考えられた。(著者抄録)