研究者詳細 - 大塚　文男

Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis. 国際誌

Yoshiaki Soejima, Yuki Otsuka, Marina Kawaguchi, Kohei Oguni, Koichiro Yamamoto, Yasuhiro Nakano, Miho Yasuda, Kazuki Tokumasu, Keigo Ueda, Kosei Hasegawa, Nahoko Iwata, Fumio Otsuka

International journal of molecular sciences 26 ( 6 ) 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism.

DOI： 10.3390/ijms26062713

Is subclinical hypothyroidism associated with cardiovascular disease in the elderly? 国際誌

Koichiro Yamamoto, Yasuhiro Nakano, Yoshiaki Soejima, Atsuhito Suyama, Kohei Oguni, Kou Hasegawa, Fumio Otsuka

Endocrine connections 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Subclinical hypothyroidism (SCH) is diagnosed when thyroid function tests show that the serum thyrotropin (TSH) level is elevated and the serum free thyroxine (FT4) level is normal. SCH is mainly caused by Hashimoto's thyroiditis, the prevalence of which increases with aging. Recently, it has been revealed that SCH is associated with risk factors for cardiovascular diseases (CVDs), including atherosclerosis, dyslipidemia and hypertension, leading to cardiovascular morbidity and mortality. However, there are still controversies regarding the diagnosis and treatment of SCH in elderly patients. In this review, we present recent evidence regarding the relationship between SCH and CVD and treatment recommendations for SCH, especially in elderly patients. Studies have shown that SCH is associated with CVD and all-cause mortality. Patients aged less than 65 years showed significant associations of SCH with CVD risk and all-cause mortality, whereas patients aged 65 or older did not show such associations. It was shown that levothyroxine therapy was associated with lower all-cause mortality and cardiovascular mortality in younger SCH patients (<65-70 years) but not in SCH patients aged 65-70 years or older. In elderly SCH patients, levothyroxine treatment should be considered individually according to the patient's age, serum TSH level, hypothyroid symptoms, CVD risk, and other comorbidities. To further elucidate the impact of SCH on CVD in elderly patients, studies should be conducted using age-specific reference ranges of results of thyroid function tests, focusing on elderly patients, specific serum TSH levels, thyroid antibody status, and cardiovascular risk factors.

DOI： 10.1530/EC-24-0601

Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study. 国際誌

Kazuki Tokumasu, Nobuyoshi Matsuki, Yuki Otsuka, Yoko Sakamoto, Keigo Ueda, Yui Matsuda, Yasue Sakurada, Hiroyuki Honda, Yasuhiro Nakano, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Fumio Otsuka

Journal of clinical medicine 14 ( 4 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated.

DOI： 10.3390/jcm14041391

Crowned Dens Syndrome Triggered by Dental Treatment. 国際誌

Satoru Morita, Yuki Otsuka, Yohei Masuda, Yoshiaki Soejima, Fumio Otsuka

Clinical case reports 13 ( 2 ) e70168 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Crowned dens syndrome (CDS) is an important yet often overlooked cause of fever and neck pain, frequently leading to unnecessary examinations and treatments and misdiagnosis as infectious diseases or rheumatic diseases. The mechanism of an acute attack of CDS is not clarified completely, while it is considered that severe systemic stress can trigger inflammation caused by calcium pyrophosphate crystals. We describe a case of CDS triggered by localized physical stress to the neck and emphasize the importance of considering this condition in cases of fever and neck pain following dental treatment.

DOI： 10.1002/ccr3.70168

Interrelationships Between Plasma Levels of Brain Natriuretic Peptide and Prolonged Symptoms Due to Long COVID. 国際誌

Yohei Masuda, Yuki Otsuka, Kazuki Tokumasu, Hiroyuki Honda, Yasue Sakurada, Yui Matsuda, Yasuhiro Nakano, Ryosuke Takase, Daisuke Omura, Toru Hasegawa, Keigo Ueda, Fumio Otsuka

Journal of clinical medicine 14 ( 3 ) 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, ≤18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment.

DOI： 10.3390/jcm14030817

Efficacy in Japanese adults with growth hormone deficiency receiving weekly somapacitan or daily growth hormone: results from phase 3 REAL 1 trial. 国際誌

Fumio Otsuka, Michael Højby Rasmussen, Takaaki Endo, Claus Sværke, Shigeyuki Tahara, Gudmundur Johannsson

Frontiers in endocrinology 16 1534891 - 1534891 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Somapacitan is a long-acting growth hormone (GH) derivative approved for once-weekly treatment of adult GH deficiency (AGHD). This study aimed to evaluate the efficacy and safety of somapacitan and daily GH in Japanese individuals with AGHD. METHODS: This subgroup study included the 34-week main period of the multinational, randomized, parallel-group, phase 3 trial, REAL 1 (NCT02229851). Participants received once-weekly somapacitan or daily GH (Norditropin®), both administered subcutaneously. Investigators and trial sites were blinded. A total of 36 Japanese GH-naïve individuals with AGHD were allocated to somapacitan or daily GH (excluding the placebo group of the global trial). Endpoints included change in truncal fat percentage to week 34 measured using dual-energy x-ray absorptiometry, as well as other body composition measures. Insulin-like growth factor I standard deviation score values were used for dose titration. RESULTS: In total, 36 Japanese individuals were included (18 and 18 in the somapacitan and daily GH group, respectively). 35 completed the main period (34 weeks). Mean (SD) change from baseline to week 34 in truncal fat percentage was -2.23 (2.50) %-points in the somapacitan group and -2.12 (4.21) %-points in the daily GH group. Other body composition measures also improved in both groups, including reduced visceral fat and increased lean body mass. Somapacitan was well tolerated, with a safety profile similar to daily GH. CONCLUSIONS: In Japanese treatment-naïve individuals with AGHD, once-weekly somapacitan demonstrated similar efficacy and safety to daily GH after 34 weeks of treatment. Somapacitan provides an effective alternative to daily GH in AGHD. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov, identifier NCT02229851.

DOI： 10.3389/fendo.2025.1534891

Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review. 査読国際誌

Shinnosuke Fukushima, Hideharu Hagiya, Kazuyoshi Gotoh, Shuma Tsuji, Koji Iio, Hidemasa Akazawa, Osamu Matsushita, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024年12月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. METHODS: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including "Corynebacterium", "Daptomycin", and "Resistance", in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. RESULTS: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8%), and prosthetic device-associated infections accounted for 66.7% of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71% to 100%) within 24 hours of incubation, compared to other Corynebacterium strains CONCLUSION: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.

DOI： 10.1016/j.jiac.2024.12.004

Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic. 査読国際誌

Yasue Sakurada, Yui Matsuda, Kanon Motohashi, Toru Hasegawa, Yuki Otsuka, Yasuhiro Nakano, Kazuki Tokumasu, Koichiro Yamamoto, Naruhiko Sunada, Hiroyuki Honda, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Journal of psychosomatic obstetrics and gynaecology 45 ( 1 ) 2305899 - 2305899 2024年12月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated. METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances. RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints. CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

DOI： 10.1080/0167482X.2024.2305899

Oral calcium supplementation versus placebo in mitigating citrate reactions during apheresis: an open-label randomized control trial

Masaya Abe, Keiko Fujii, Nobuharu Fujii, Toshiharu Mitsuhashi, Takuya Fukumi, Yuichi Sumii, Maiko Kimura, Tomohiro Urata, Takumi Kondo, Fumio Otsuka, Yoshinobu Maeda

Hematology, Transfusion and Cell Therapy 2024年12月

圧迫骨折と女性化乳房を契機に精査し、AGHDを合併した新規KAL2バリアントによるKallmann症候群と診断しえた1例

副島佳晃, 大塚勇輝, 川口満理奈, 大國皓平, 中野靖浩, 安田美帆, 徳増一樹, 植田圭吾, 長谷川高誠, 大塚文男

日本内分泌学会雑誌 100 ( 4 ) 1077 - 1077 2024年12月

全身倦怠感を契機に発見され、可逆性の下垂体機能低下を呈した神経梅毒の1例

大國皓平, 中野靖浩, 副島佳晃, 須山敦仁, 山本紘一郎, 安田美帆, 長谷川功, 大塚文男

日本内分泌学会雑誌 100 ( 4 ) 1078 - 1078 2024年12月

Clinical Characteristics of Persistent Hypophosphatasemia Uncovered in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital. 査読国際誌

Shintaro Fujiwara, Yuki Otsuka, Masanori Furukawa, Akihito Higashikage, Fumio Otsuka

Journal of clinical medicine 13 ( 23 ) 2024年11月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Hypophosphatasemia is often overlooked despite its potential to indicate underlying pathologies. The aim of this study was to determine the prevalence of persistent hypophosphatasemia in a large, urban, multi-specialty hospital population and characterize the clinical and laboratory findings in adult patients with this condition. Methods: In this retrospective observational study, the results of 424,434 alkaline phosphatase (ALP) tests in 50,136 patients aged ≥18 years that were performed at Okayama University Hospital between July 2020 and October 2023 were analyzed. Persistent hypophosphatasemia was defined as consistently low ALP levels (≤40 IU/L) for 28 days with a minimum recorded level of ≤35 IU/L. Results: Persistent hypophosphatasemia was detected in 273 patients (0.54% of the tested patients), and the patients with persistent hypophosphatasemia included a higher proportion of females (72.5% vs. 52.9% in the people without persistent hypophosphatasemia; chi-squared test, p < 0.01) and had a younger median age (51 years vs. 63 years; Mann-Whitney U test, p < 0.01) than those in the overall tested population. The common causes of persistent hypophosphatasemia were cancer (30%), glucocorticoid use (21%), and immunosuppressants (16%). Notably, 38 patients (14%) had no apparent cause for low ALP values. These patients were categorized on the basis of their clinical characteristics, with some patients presenting symptoms potentially related to adult hypophosphatasia. Conclusions: This study provides prevalence and insights into the causes and characteristics of persistent hypophosphatasemia in a Japanese tertiary care setting. While most cases were associated with known causes, patients with unexplained hypophosphatasemia and symptoms such as chronic pain, muscle weakness, and general fatigue could have adult hypophosphatasia. In such cases, comprehensive evaluation and further investigation for hypophosphatasia should be considered. Persistent hypophosphatasemia of undetermined etiology could be a crucial initial step in diagnostic algorithms for this condition.

DOI： 10.3390/jcm13237078

Human Papillomavirus vaccination awareness and uptake among healthcare students in Japan. 査読国際誌

Madoka Shimbe, Yuki Otsuka, Hideharu Hagiya, Yoichi Yamada, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024年11月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The vaccination rate for HPV (Human Papillomavirus) has remained significantly low in Japan because of the administrative suspension of active recommendation. This study investigates the awareness and uptake of the HPV vaccine among healthcare students in Japan following the reinstatement of active recommendation for young women in April 2022. METHODS: A web-based survey was administered to 2567 healthcare students from Okayama and Shujitsu Universities in Japan in July 2023. The survey assessed participants' backgrounds, immunization status, awareness of vaccine recommendations, and knowledge of cervical cancer across various demographics, including sex, academic year, and department (Medicine, Health Science, Pharmaceutical, and Dentistry). RESULTS: The response rate was 36.3 % (933 students; 181 male, 739 female, and 13 unspecified gender). The overall immunization rate among female students was 55.6 %, with higher rates observed in medical (73.8 %) and dental (63.0 %) students. Awareness of the government's change in vaccine recommendation was notably high among female and senior male students. Over half of the female students (54.7 %) reported receiving vaccinations based on their parents' advice. Among those unvaccinated but interested in future immunization, concerns about adverse reactions (47.4 %) and challenges in scheduling vaccinations (29.1 %) were predominant. CONCLUSION: Healthcare students exhibited a higher HPV vaccination rate than the general population. Ongoing education to improve vaccine literacy is crucial for augmenting HPV vaccination rates in Japan.

DOI： 10.1016/j.jiac.2024.11.004

Trends in adverse effects of medical treatment in Paediatric populations in the United States: A global burden of disease study, 2000–2019 査読

ブロスマブを高用量かつ長期投与中の腫瘍性骨軟化症の1例

中野靖浩, 越智可奈子, 山本紘一郎, 須山敦仁, 副島佳晃, 大國皓平, 長谷川功, 大塚文男

日本内分泌学会雑誌 100 ( 2 ) 678 - 678 2024年10月

一過性の縮小を呈し悪性リンパ腫が疑われた左副腎偶発腫の1例

佐住洋祐, 中野靖浩, 加藤篤之, 須山敦仁, 大國皓平, 山本紘一郎, 安田美帆, 越智可奈子, 長谷川功, 本多寛之, 川合裕也, 藤井伸治, 大塚文男

日本内分泌学会雑誌 100 ( 2 ) 607 - 607 2024年10月

Threat of MRSA bacteremia still matters: a propensity score matching analysis. 査読国際誌

Shinnosuke Fukushima, Hideharu Hagiya, Naoki Kuninaga, Yuto Haruki, Haruto Yamada, Yoshitaka Iwamoto, Masayo Yoshida, Kota Sato, Yoshihisa Hanayama, Shuichi Tanaka, Tomoko Miyoshi, Yuki Otsuka, Keigo Ueda, Fumio Otsuka

Infection 2024年9月

Shintaro Fujiwara, Emily Leibovitch, Ko Harada, Yoshito Nishimura, Russell Woo, Fumio Otsuka, Akshaya Srikanth Bhagavathula

Paediatric and Perinatal Epidemiology 2024年9月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Abstract

Background

Adverse effects of medical treatment (AEMT) pose significant risks to paediatric patients. However, the mortality trends associated with AEMT in this population have been unclear.

Objective

We aimed to clarify the trends in the incidence, disability‐adjusted life years (DALYs) and mortality rates of AEMT for children in the US from 2000 to 2019.

Methods

Data were retrieved from the Global Burden of Disease study 2019. We estimated age‐standardized incidence, DALYs and mortality rates of paediatric AEMT per 100,000 children in the US using a Bayesian meta‐regression model. We also analysed incidence, DALYs and mortality in different age groups, and employed Joinpoint regression models to assess the age‐ and sex‐specific trends.

Results

The number of deaths due to AEMT in children, the number of cases, and DALYs were 105.1, 551,076 and 145,555 in 2019, decreased by 37.5%, 6% and 28% from those in 2000, respectively. Age‐standardized mortality rates decreased across all age groups, while the incidence increased across all age groups with an average annual percentage change (AAPC) of 2.2% in those children <1 year and 4.5% in 5–9 years of age. The increases in DALYs over time was higher in children aged 1–4 years (AAPC: 0.51, 95% CI: 0.47, 0.62) and 5–9 years (AAPC: 0.33, 95% CI: 0.15, 0.50), with the 1–4 year age group being the highest.

Conclusion

The study reveals declining AEMT mortality but rising incidence and DALYs, emphasizing a disproportionate burden in <1, 1–4 and 5–9 years. To develop effective mitigation strategies, future research is warranted to identify the causes of increased AEMT in children, especially young males.

DOI： 10.1111/ppe.13116

出血性脳梗塞,肺塞栓,深部静脈血栓症を合併したCOVID-19の1例

A Case of Systemic Lupus Erythematosus Initially Presenting as Lupus Enteritis Triggered by Pregnancy 査読

Tomoko Miyoshi, Fumio Otsuka

JOURNAL OF HOSPITAL GENERAL MEDICINE 6 ( 6 ) 154 - 157 2024年9月

COVID-19罹患後症状の女性患者にみられる月経異常とストレスの関係

櫻田泰江, 松田祐依, 長谷川徹, 大塚勇輝, 中野靖浩, 徳増一樹, 砂田匠彦, 本橋花音, 本多寛之, 植田圭吾, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増2 ) 263 - 263 2024年9月

長谷川功, 山本紘一郎, 中本健太, 平佑貴, 庵谷紘美, 中野靖浩, 萩谷英大, 大塚文男

日本病院総合診療医学会雑誌 20 ( 5 ) 289 - 294 2024年9月

記述言語：日本語出版者・発行元：(一社)日本病院総合診療医学会

52歳男性。COVID-19発症7日後に経皮的動脈血酸素飽和度94%(リザーバー10L/分投与下),右眼球共同偏倚と左半側空間無視,左上下肢完全麻痺をきたし搬送された。単純CTでは頭部で右中大脳動脈領域低吸収域を認め,胸部では両側広範囲の末梢優位のすりガラス影を認めた。造影CTでは右下肺動脈と左大腿静脈・膝窩静脈に血栓を認め,脳梗塞と肺塞栓症・深部静脈血栓症を合併した重症COVID-19と診断した。経過中に出血性脳梗塞を発症するも救命し得た。脳梗塞・肺塞栓を合併したCOVID-19では出血性脳梗塞の発症を念頭に慎重なフォローが必要である。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J05937&link_issn=&doc_id=20241218260009&doc_link_id=10.60227%2Fjhgmwabun.20.5_289&url=https%3A%2F%2Fdoi.org%2F10.60227%2Fjhgmwabun.20.5_289&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

COVID-19罹患後症状の患者における就労状況への影響

松田祐依, 櫻田泰江, 大塚勇輝, 徳増一樹, 中野靖浩, 砂田匠彦, 本多寛之, 長谷川徹, 高瀬了輔, 大村大輔, 植田圭吾, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増2 ) 263 - 263 2024年9月

Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report. 査読国際誌

Kohei Oguni, Shinnosuke Fukushima, Hideharu Hagiya, Atsushi Kato, Atsuhito Suyama, Takehiro Iwata, Yoshia Miyawaki, Sawako Ono, Koji Iio, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease.

DOI： 10.1016/j.jiac.2024.08.009

Postgraduate Year Two Medical Residents' Awareness of Personal Development as a Physician during the Management of Inpatients: A Qualitative Study. 査読国際誌

Kazuki Tokumasu, Haruo Obara, Takanobu Hirosawa, Hiroko Ogawa, Fumio Otsuka

Healthcare (Basel, Switzerland) 12 ( 16 ) 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Clinical experiences, helping relationships, and reflection are key factors for personal development for physicians. However, few studies have shown which experiences are important for personal growth and how medical residents specifically use their experiences for personal growth. The aim of this study was to identify from the medical residents' perspective which clinical experiences contribute to their personal development. We employed a qualitative design, conducting semi-structured interviews with ten postgraduate year two medical residents at a Japanese teaching hospital. The interviews were transcribed in interview memos, anonymized, and subjected to reflective thematic analysis to generate themes relevant to personal and professional development. Successful clinical experiences with autonomy and responsibility in clinical management were shown to be essential points for personal development as a physician. Autonomy in this study was the attitude of making one's own choices when managing patients. Responsibility was the obligation of the resident to take charge of a patient. Instructing junior trainees, appreciation received from patients, and approval granted by attending physicians reinforced their feelings of personal growth. The realization of what experiences and concepts influence medical residents' personal growth and development will make their professional development more effective.

DOI： 10.3390/healthcare12161621

Scopus

Effectiveness of Sensing Gloves-Applied Virtual Reality Education System on Hand Hygiene Practice: A Randomised Controlled Trial. 査読国際誌

Mahiro Izumi, Hideharu Hagiya, Yuki Otsuka, Yoshiaki Soejima, Shinnosuke Fukushima, Mitsunobu Shibata, Satoshi Hirota, Toshihiro Koyama, Fumio Otsuka, Akio Gofuku

American journal of infection control 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: We developed a virtual reality (VR) education system and evaluated its clinical utility for promoting hand hygiene practices. METHODS: This prospective, two-week, randomised controlled study conducted at Okayama University Hospital, Japan, from November 2023 to January 2024, involved 22 participants (18 medical students and four residents). A fully immersive 360° VR system (VIVE Pro Eye) using a head-mounted display and sensing gloves was used to develop three healthcare tasks in a virtual patient room-Environmental Cleaning, Gauze Exchange, and Urine Collection. After monitoring all participants' baseline usage data of portable hand-rubbing alcohol in the first week, we randomly assigned them into 1:1 groups (VR training and video lecture groups). The primary outcome was differences in hand-rubbed alcohol use before and after intervention. RESULTS: Before the intervention, alcohol use did not significantly differ between both groups. After the intervention, a significant increase in alcohol use was observed in the VR training group (median: 8.2 g vs. 16.2 g; p=0.019) but not in the video lecture group. CONCLUSION: Our immersive 360° VR education system enhanced hand hygiene practices. Infection prevention and control practitioners and digital technology experts must collaborate to advance the development of superior educational devices and content.

DOI： 10.1016/j.ajic.2024.08.003

Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID. 査読国際誌

Atsushi Kato, Kazuki Tokumasu, Koichiro Yamamoto, Yuki Otsuka, Yasuhiro Nakano, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Ryosuke Takase, Keigo Ueda, Fumio Otsuka

Scientific reports 14 ( 1 ) 17025 - 17025 2024年7月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

DOI： 10.1038/s41598-024-67815-y

New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review. 査読国際誌

Lutfun Nahar, Hideharu Hagiya, Kazuyoshi Gotoh, Md Asaduzzaman, Fumio Otsuka

Journal of clinical medicine 13 ( 14 ) 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.

DOI： 10.3390/jcm13144199

Reliability and Validity of the Japanese Version of the Fatigue Assessment Scale. 査読

Kazuki Tokumasu, Nobuyoshi Matsuki, Hirohisa Fujikawa, Yoko Sakamoto, Fumio Otsuka

Internal medicine (Tokyo, Japan) 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective General fatigue is one of the most frequent chief complaints in primary care, and an accurate assessment of fatigue has a direct impact on a patient's quality of life and treatment decisions. The Fatigue Assessment Scale (FAS), a measure of general fatigue, is useful for assessing fatigue in diverse cultures and diseases. However, there has been no study showing the reliability and validity of the scale in the Japanese context. The present study assessed the reliability and validity of the Japanese version of the FAS. Methods This study was conducted on 649 patients with long COVID who had a high frequency of general fatigue. To test the structural validity of the FAS, the patients were randomly divided into two groups: one in which an exploratory factor analysis (EFA) was conducted and one in which a confirmatory factor analysis (CFA) was conducted. Cronbach's alpha was calculated to assess internal consistency reliability. Results As 58 patients had missing values, we analyzed the data of 591 patients. The EFA led to an FAS comprising two factors. The CFA showed an acceptable fit for this two-factor model. The internal consistency was found to be good (Cronbach's alpha =0.89). Conclusion This study verified the structural validity and internal consistency and reliability of the Japanese version of the FAS. The results indicate that the Japanese version of the FAS is useful for assessing general fatigue in patients with long COVID in Japan.

DOI： 10.2169/internalmedicine.4101-24

Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID: A Retrospective Study in Japan. 査読国際誌

Sho Yokoyama, Hiroyuki Honda, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Yasue Sakurada, Yui Matsuda, Naruhiko Sunada, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Yoshiaki Soejima, Keigo Ueda, Masayuki Kishida, Fumio Otsuka

Journal of clinical medicine 13 ( 14 ) 2024年7月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients' backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m2; p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID.

DOI： 10.3390/jcm13144099

学生視点から得られた岡山大学病院総合内科・総合診療科における臨床実習教育の気づき質的研究

山本幸近, 徳増一樹, 大塚文男

医学教育 55 ( Suppl. ) 231 - 231 2024年7月

コロナ禍における医学生のストレス知覚についての研究対面とオンラインのコミュニケーションによる違い(Medical students' stress perception on in-person/online communication during the COVID-19 pandemic)

徳増一樹, 西村義人, 坂本陽子, 小比賀美香子, 片岡仁美, 大塚文男

医学教育 55 ( Suppl. ) 223 - 223 2024年7月

漢方医学への学習意欲向上プロセスの探索混合研究(Exploring the process of motivation for learning about Kampo medicine: A mixed method study)

徳増一樹, 植田圭吾, 松田祐依, 大塚勇輝, 川口満理奈, 大塚文男

医学教育 55 ( Suppl. ) 222 - 222 2024年7月

医学生の医療面接における表情解析AIを用いた検討

越智可奈子, 三好智子, 大塚勇輝, 小崎吉訓, 山下範之, 伊野英男, 大塚文男

医学教育 55 ( Suppl. ) 292 - 292 2024年7月

Changes in Working Situations of Employed Long COVID Patients: Retrospective Study in Japanese Outpatient Clinic. 査読国際誌

Yui Matsuda, Yasue Sakurada, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Naruhiko Sunada, Hiroyuki Honda, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Keigo Ueda, Fumio Otsuka

Journal of clinical medicine 13 ( 13 ) 2024年6月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: The present study aimed to uncover the impact of long COVID on the working situations of Japanese patients. Methods: Changes in the working situations of the patients who visited our long COVID clinic were evaluated from medical records for the aspects of physical status, quality of life (QOL), and mental conditions. Results: Of 846 long COVID patients who visited our clinic from February 2021 to December 2023, 545 employed patients aged between 18 and 65 years were included in this study. A total of 295 patients (54.1%) with long COVID (median age: 43 years, female: 55.6%) experienced changes in their working status. Those patients included 220 patients (40.4%) who took a leave of absence, 53 patients (9.7%) who retired, and 22 patients (4%) with reduced working hours. Most of the patients (93.2%) with changes in working conditions had mild disease severity in the acute phase of COVID-19. The majority of those patients with mild disease severity (58.8%) were infected in the Omicron-variant phase and included 65.3% of the female patients. The major symptoms in long COVID patients who had changes in their working situations were fatigue, insomnia, headache, and dyspnea. Scores indicating fatigue and QOL were worsened in long COVID patients who had changes in their working situations. In addition, 63.7% of the long COVID patients with changes in their working situations had decreases in their incomes. Conclusions: Changes in the working situation of long COVID patients who were employed had a negative impact on the maintenance of their QOL.

DOI： 10.3390/jcm13133809

Evaluation of ChatGPT-Generated Differential Diagnosis for Common Diseases With Atypical Presentation: Descriptive Research 査読

Kiyoshi Shikino, Taro Shimizu, Yuki Otsuka, Masaki Tago, Hiromizu Takahashi, Takashi Watari, Yosuke Sasaki, Gemmei Iizuka, Hiroki Tamura, Koichi Nakashima, Kotaro Kunitomo, Morika Suzuki, Sayaka Aoyama, Shintaro Kosaka, Teiko Kawahigashi, Tomohiro Matsumoto, Fumina Orihara, Toru Morikawa, Toshinori Nishizawa, Yoji Hoshina, Yu Yamamoto, Yuichiro Matsuo, Yuto Unoki, Hirofumi Kimura, Midori Tokushima, Satoshi Watanuki, Takuma Saito, Fumio Otsuka, Yasuharu Tokuda

JMIR Medical Education 10 e58758 - e58758 2024年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：JMIR Publications Inc.

Abstract

Background

The persistence of diagnostic errors, despite advances in medical knowledge and diagnostics, highlights the importance of understanding atypical disease presentations and their contribution to mortality and morbidity. Artificial intelligence (AI), particularly generative pre-trained transformers like GPT-4, holds promise for improving diagnostic accuracy, but requires further exploration in handling atypical presentations.

Objective

This study aimed to assess the diagnostic accuracy of ChatGPT in generating differential diagnoses for atypical presentations of common diseases, with a focus on the model’s reliance on patient history during the diagnostic process.

Methods

We used 25 clinical vignettes from the Journal of Generalist Medicine characterizing atypical manifestations of common diseases. Two general medicine physicians categorized the cases based on atypicality. ChatGPT was then used to generate differential diagnoses based on the clinical information provided. The concordance between AI-generated and final diagnoses was measured, with a focus on the top-ranked disease (top 1) and the top 5 differential diagnoses (top 5).

Results

ChatGPT’s diagnostic accuracy decreased with an increase in atypical presentation. For category 1 (C1) cases, the concordance rates were 17% (n=1) for the top 1 and 67% (n=4) for the top 5. Categories 3 (C3) and 4 (C4) showed a 0% concordance for top 1 and markedly lower rates for the top 5, indicating difficulties in handling highly atypical cases. The χ² test revealed no significant difference in the top 1 differential diagnosis accuracy between less atypical (C1+C2) and more atypical (C3+C4) groups (χ²₁=2.07; n=25; P=.13). However, a significant difference was found in the top 5 analyses, with less atypical cases showing higher accuracy (χ²₁=4.01; n=25; P=.048).

Conclusions

ChatGPT-4 demonstrates potential as an auxiliary tool for diagnosing typical and mildly atypical presentations of common diseases. However, its performance declines with greater atypicality. The study findings underscore the need for AI systems to encompass a broader range of linguistic capabilities, cultural understanding, and diverse clinical scenarios to improve diagnostic utility in real-world settings.

DOI： 10.2196/58758

Disseminated septic arthritis caused by Ureaplasma urealyticum in an immunocompromised patient with hypogammaglobulinemia after rituximab therapy. 査読国際誌

Kohei Oguni, Shinnosuke Fukushima, Yuki Otsuka, Yoshiaki Soejima, Marina Kawaguchi, Yosuke Sazumi, Takumi Fujimori, Koji Iio, Noriyuki Umakoshi, Kazuki Yamada, Hideharu Hagiya, Fumio Otsuka

Infection 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Ureaplasma urealyticum is a rare pathogen associated with septic arthritis that predominantly affects patients with hypogammaglobulinemia. Bacterial identification of fastidious organisms is challenging because they are undetectable by routine culture testing. To the best of our knowledge, this is the first report of septic arthritis induced by U. urealyticum infection in Japan. CASE DESCRIPTION: We describe the case of a 23-year-old Japanese female with secondary hypogammaglobulinemia (serum immunoglobulin level < 500 mg/dL), identified 8 years after treatment with rituximab. The patient presented with persistent fever and polyarthritis that were unresponsive to ceftriaxone and prednisolone. Contrast-enhanced computed tomography and gallium-67 scintigraphy revealed effusion and inflammation in the left sternoclavicular, hip, wrist, knee, and ankle joints. Although Gram staining and bacterial culture of the drainage fluid from the left hip joint were negative, the condition exhibited characteristics of purulent bacterial infection. The patient underwent empirical treatment with doxycycline, and her symptoms promptly resolved. Subsequent 16S ribosomal RNA (rRNA) gene sequencing of the joint fluid confirmed the presence of U. urealyticum, leading to the diagnosis of septic arthritis. Combination therapy with doxycycline and azithromycin yielded a favorable recovery from the inflammatory status and severe arthritic pain. CONCLUSION: This case highlights U. urealyticum as a potential causative agent of disseminated septic arthritis, particularly in patients with hypogammaglobulinaemia. The 16S rRNA gene analysis proved beneficial for identifying pathogens in culture-negative specimens, such as synovial fluid, in suspected bacterial infections.

DOI： 10.1007/s15010-024-02301-1

検体検査システムを利用したEDTA依存性偽性血小板減少症患者におけるFC管の採血忘れ防止策の構築と効果

平畑嵐紀, 青江伯規, 平松舞, 日野佳弥, 青江佐佳恵, 高橋孝英, 三宅雅之, 川下隆二, 東影明人, 大塚文男

日本検査血液学会雑誌 25 ( 学術集会 ) S215 - S215 2024年6月

Benign adrenal cyst: A rare type of adrenal incidentaloma 査読

Koichiro Yamamoto, Kohei Oguni, Fumio Otsuka

Clinical Case Reports 12 ( 6 ) 2024年5月

担当区分：最終著者掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Key Clinical Message

We present a patient with hypertension who developed a rare type of incidentaloma, a benign adrenal cyst. Benign adrenal cysts are typically large; however, most are nonfunctioning and asymptomatic, and they can be managed conservatively.

DOI： 10.1002/ccr3.8914

「感染制御チームや微生物検査室がない地域医療機関」で内科専攻医が取り組んだ血液培養のコンタミネーション低減活動に関する報告

福島伸乃介, 萩谷英大, 辻健太郎, 平岩千尋, 大江啓史, 喜多真也, 太田茂, 多田龍平, 宮阪英, 角南博, 表静馬, 大塚文男

感染症学雑誌 98 ( 3 ) 306 - 310 2024年5月

Adherence to and clinical utility of "quality indicators" for Staphylococcus aureus bacteremia: a retrospective, multicenter study. 査読国際誌

Infection 2024年5月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. METHODS: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with > 600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. RESULTS: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. CONCLUSIONS: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators.

DOI： 10.1007/s15010-024-02284-z

若手総合診療医としてJMATでの能登派遣を振り返って災害医療に活かせる総合診療とは?

成人低アルカリフォスファターゼ血症の検出頻度とその特徴

藤原進太郎, 大塚勇輝, 古川雅規, 東影明人, 大塚文男

日本内分泌学会雑誌 100 ( 1 ) 351 - 351 2024年5月

随時血糖高値によるCOVID-19罹患後症状および治療期間への影響

横山将, 本多寛之, 大塚勇輝, 徳増一樹, 砂田匠彦, 松田祐依, 櫻田泰江, 高瀬了輔, 植田圭吾, 大塚文男

日本内分泌学会雑誌 100 ( 1 ) 435 - 435 2024年5月

後腹膜線維症49症例における臨床的特徴甲状腺機能に着目して

花山宜久, 安藤美穂, 大國皓平, 徳増一樹, 長谷川功, 萩谷英大, 大塚文男

日本内分泌学会雑誌 100 ( 1 ) 314 - 314 2024年5月

赤澤英将, 大塚勇輝, 藤原真治, 片岡仁美, 大塚文男

総合診療 34 ( 5 ) 560 - 563 2024年5月

オトガイ部の生検から診断に至った全身性ALアミロイドーシスの1例

坂田伽奈子, 川上佳夫, 横山恵美, 森実真, 長谷川功, 中野靖浩, 大塚文男, 白藤宜紀

日本皮膚科学会雑誌 134 ( 6 ) 1711 - 1711 2024年5月

Long COVIDに見られる起立性調節障害の臨床的特徴

加藤篤之, 徳増一樹, 山本紘一郎, 大塚勇輝, 副島佳晃, 須山敦仁, 大國皓平, 砂田匠彦, 松田祐依, 櫻田泰江, 植田圭吾, 大塚文男

日本内分泌学会雑誌 100 ( 1 ) 436 - 436 2024年5月

随時血糖高値によるCOVID-19罹患後症状および治療期間への影響

横山将, 本多寛之, 大塚勇輝, 徳増一樹, 砂田匠彦, 松田祐依, 櫻田泰江, 高瀬了輔, 植田圭吾, 大塚文男

日本内分泌学会雑誌 100 ( 1 ) 435 - 435 2024年5月

後腹膜線維症49症例における臨床的特徴甲状腺機能に着目して

花山宜久, 安藤美穂, 大國皓平, 徳増一樹, 長谷川功, 萩谷英大, 大塚文男

日本内分泌学会雑誌 100 ( 1 ) 314 - 314 2024年5月

漢方医学への学習意欲向上プロセスの探索医学生の漢方教育×LongCOVIDプロジェクトを通して

徳増一樹, 植田圭吾, 大塚勇輝, 大塚文男

日本東洋医学雑誌 75 ( 別冊 ) 330 - 330 2024年5月

日本における播種性クリプトコッカス症の疫学的特徴ならびに地域性・季節性およびトレンドの解析

赤澤英将, 福島伸乃介, 萩谷英大, 大塚文男

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集 98回・72回 np193 - np193 2024年5月

伝播性薬剤耐性HIVにより進行性多巣性白質脳症を発症した一例

川口満理奈, 萩谷英大, 大塚勇輝, 福島伸乃介, 大塚文男

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集 98回・72回 np333 - np333 2024年5月

黄色ブドウ球菌菌血症(SAB)に対する診療の質指標(Quality Indicator)に関する多施設研究

福島伸乃介, 萩谷英大, 大塚勇輝, 山田晴士, 岩本佳隆, 佐藤恒太, 大塚文男

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集 98回・72回 np210 - np210 2024年5月

Prostate abscess caused by ESBL-producing E. coli successfully treated with fosfomycin monotherapy. 査読国際誌

Shinnosuke Fukushima, Yuki Otsuka, Hideharu Hagiya, Naoto Nishikawa, Fumio Otsuka

International journal of antimicrobial agents 107182 - 107182 2024年4月

ISO15189の要求事項に適応した機材管理システムの構築と評価査読

三宅雅之, 飯尾耕治, 池田亮, 東影明人, 大塚文男

医学検査 73 ( 2 ) 316 - 322 2024年4月

担当区分：最終著者記述言語：日本語出版者・発行元：(一社)日本臨床衛生検査技師会

当院の検査部門は2007年7月にISO15189の認定を取得した。これまでISO15189の認定を維持管理してきたなかで,内部監査での機材管理に関連する不適合数が減少しないことが問題となった。そこで,機材管理を簡便かつ適切に行える機材管理システムの開発を行った。当院の医療用端末にインストールされているMicrosoft Accessを用いてリレーショナルデータベース(RDB)を独自に構築し,それに付属するVisual Basic for Applications(VBA)を用いてアプリケーション開発を行った。RDB構築にあたってISO15189の要求事項を過不足なく管理できることを意識し,なおかつ変更履歴を容易に確認できるようにするため一部のテーブルでは世代管理の仕組みを取り入れた。構築した機材管理システムは2019年6月から運用開始し,これまで複数回のバージョンアップを繰り返しながら稼動している。内部監査での機材管理に関連する不適合数では,機材管理システムを導入する以前の2013年度では13件あった不適合数が導入後の2022年度では7件まで減少した。機材管理システムを導入したことにより適切に機材管理できるようになったと考えられる。また,独自に開発したシステムであるためバグ修正や機能追加が容易であり,要求事項を満たし,かつ今の検査室にとって適切なシステムを維持しやすいと考えられた。(著者抄録)

慢性甲状腺炎と副腎クリーゼを背景に発症した麻痺性イレウスにLT4静注が奏効した1例

副腎摘除後に血糖コントロールが著明に改善した高齢クッシング症候群の1例

長谷川功, 山本紘一郎, 大國皓平, 中野靖浩, 安田美帆, 本多寛之, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 67 ( Suppl.1 ) S - 299 2024年4月

チルゼパチド導入が治療負担感軽減に有用と思われた若年肥満2型糖尿病男性の2例

本多寛之, 山本紘一郎, 大國皓平, 中野靖浩, 安田美帆, 長谷川功, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 67 ( Suppl.1 ) S - 336 2024年4月

中野靖浩, 大國皓平, 長谷川功, 越智可奈子, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1288 - 1288 2024年4月

腺腫様結節による甲状腺中毒症を呈したPlummer病の1例

加藤篤之, 大國皓平, 中野靖浩, 長谷川功, 越智可奈子, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1295 - 1295 2024年4月

チルゼパチド導入が治療負担感軽減に有用と思われた若年肥満2型糖尿病男性の2例

本多寛之, 山本紘一郎, 大國皓平, 中野靖浩, 安田美帆, 長谷川功, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 67 ( Suppl.1 ) S - 336 2024年4月

A Case of Persistent Hiccups Induced by an Enlarging Hepatic Cyst Underneath the Diaphragm. 査読国際誌

Wataru Ando, Yuki Otsuka, Fumio Otsuka

Cureus 16 ( 4 ) e58278 2024年4月

担当区分：最終著者記述言語：英語

Although hiccups are regularly self-limited and rarely life-threatening, prolonged hiccups are bothersome, which can significantly decrease the quality of life. Here, we report a case of persistent hiccups coexisting with an enlarging liver cyst situated just below the diaphragm in a patient with autosomal dominant polycystic kidney disease (ADPKD). No other underlying etiologies related to the symptoms were suspected. The cyst was difficult to drain surgically and the patient continued with symptomatic treatment. Although rare, hepatic cysts should be considered a potential cause of prolonged hiccups in patients with ADPKD. We emphasize the significance of systematically excluding potential etiologies that cause prolonged hiccups and considering appropriate therapeutic interventions.

DOI： 10.7759/cureus.58278

高度のQT延長が副腎摘除術後に改善した原発性アルドステロン症の1例

高瀬了輔, 中野靖浩, 須山敦仁, 加藤篤之, 佐住洋祐, 長谷川功, 前川清明, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1500 - 1500 2024年4月

副腎摘除後に血糖コントロールが著明に改善した高齢クッシング症候群の1例

長谷川功, 山本紘一郎, 大國皓平, 中野靖浩, 安田美帆, 本多寛之, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 67 ( Suppl.1 ) S - 299 2024年4月

腰椎圧迫骨折を契機に低アンドロゲン血症が判明した中年男性の1例

副島佳晃, 大塚勇輝, 川口満理奈, 大國晧平, 中野靖浩, 安田美帆, 徳増一樹, 植田圭吾, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1500 - 1500 2024年4月

NVX-CoV2373ワクチン投与後に血管浮腫様の眼瞼浮腫を生じた1例

松本真理, 川上佳夫, 三宅智子, 平井陽至, 森実真, 片岡仁美, 大塚文男

西日本皮膚科 86 ( 2 ) 198 - 198 2024年4月

腰椎圧迫骨折を契機に低アンドロゲン血症が判明した中年男性の1例

副島佳晃, 大塚勇輝, 川口満理奈, 大國晧平, 中野靖浩, 安田美帆, 徳増一樹, 植田圭吾, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1500 - 1500 2024年4月

下垂体後葉ホルモンによる顆粒膜細胞のプロゲステロン合成調節と卵胞BMPの関与

山本紘一郎, 中野靖浩, 岩田菜穂子, 副島佳晃, 須山敦仁, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1545 - 1545 2024年4月

慢性甲状腺炎と副腎クリーゼを背景に発症した麻痺性イレウスにLT4静注が奏効した1例

中野靖浩, 大國皓平, 長谷川功, 越智可奈子, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1288 - 1288 2024年4月

腺腫様結節による甲状腺中毒症を呈したPlummer病の1例

加藤篤之, 大國皓平, 中野靖浩, 長谷川功, 越智可奈子, 大塚文男

日本内分泌学会雑誌 99 ( 5 ) 1295 - 1295 2024年4月

Enhancing Medical Interview Skills through AI Simulated Patient Interactions: Non-Randomized Controlled Trial 査読

Akira Yamamoto, Masahide Koda, Hiroko Ogawa, Tomoko Miyoshi, Yoshinobu Maeda, Fumio Otsuka, Hideo Ino

JMIR Med Educ 10 ( e58753 ) 1 - 12 2024年3月

出版者・発行元：JMIR Publications Inc.

BACKGROUNDMedical interviewing is a critical skill in clinical practice, yet opportunities for practical training are limited in Japanese medical schools, necessitating urgent measures. Given advancements in AI technology, its application in the medical field is expanding. However, reports on its application in medical interviews in medical education are scarce. OBJECTIVEThis study aimed to investigate whether medical students' interview skills could be improved by engaging with AI-simulated patients using large language models (LLMs), including the provision of feedback. METHODSA simulation program using LLMs was provided to 35 fourth-year medical students in Japan in 2023. As a control group, 110 fourth-year medical students from 2022 who did not participate in the intervention were selected. The primary outcome was the score on the pre-Clinical Clerkship Objective Structured Clinical Examination (pre-CC OSCE), a national standardized clinical skills examination, in medical interviewing. Secondary outcomes included surveys such as Simulation-Based Training Quality Assurance Tool (SBT-QA10). RESULTSThe AI intervention group showed significantly higher scores on medical interviews than the control group (AI group vs. control group: median 28.0 vs. 27.0, p = 0.01). There was a trend of inverse correlation between the SBT-QA10 and pre-CC OSCE scores (regression coefficient -2.0 to -2.1). No significant safety concerns were observed. CONCLUSIONSEducation through medical interviews using AI-simulated patients has demonstrated safety and a certain level of educational effectiveness, suggesting promising prospects for multifaceted applications in the field of medical education.

DOI： 10.2196/preprints.58753

Calcium polystyrene sulfonate-induced rectal ulcer causing E. coli native-valve infective endocarditis. 査読

Shinnosuke Fukushima, Hideharu Hagiya, Hiroyuki Honda, Tomoharu Ishida, Ryohei Shoji, Kou Hasegawa, Fumio Otsuka

Clinical Journal of Gastroenterology 2024年3月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Escherichia coli-associated native-valve infective endocarditis is a rare disease that affects elderly patients with underlying risk factors such as diabetes mellitus, malignancy, and renal failure. Long-term use of calcium polystyrene sulfonate is a potential risk factor for gastrointestinal mucosal damage or even colorectal ulcers. Herein, we describe a fatal case of a 66-year-old Japanese man with diabetes mellitus and renal failure who was prescribed calcium polystyrene sulfonate (CPS) for 11 years and developed a CPS-induced rectal ulcer, leading to E. coli native-valve infective endocarditis. The patient was admitted to our hospital due to acute-onset impaired consciousness. As a result of the systemic investigation, he was diagnosed with E. coli bacteremia accompanied by multiple cerebral infarctions and an acute hemorrhagic rectal ulcer. Transesophageal echocardiography revealed a 20-mm vegetative structure on the mitral valve, resulting in a final diagnosis of E. coli-associated infective endocarditis. After rectal resection, mitral valve replacement surgery was performed; however, the patient died shortly after surgery. Pathological findings of the resected rectum showed deposition of a basophilic crystalline material suggesting the presence of CPS. Our case highlights the potential risk of colorectal ulcers in a long-term CPS user, which can trigger bacterial translocation and endocarditis as fatal complications.

DOI： 10.1007/s12328-024-01949-4

Idiopathic ventricular tachycardia detected after coronavirus disease 2019 査読

Koichiro Yamamoto, Koji Nakagawa, Fumio Otsuka

Journal of General and Family Medicine 2024年3月

Zinc deficiency is a potential risk factor for COVID-19 progression to pneumonia requiring oxygen therapy. 査読国際誌

Koji Fujita, Kazuki Ocho, Tomoka Kadowaki, Takashi Yorifuji, Hideharu Hagiya, Fumio Otsuka

Journal of Infection and Chemotherapy 30 ( 10 ) 978 - 982 2024年3月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19. METHODS: The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 μg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders. RESULTS: Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors. CONCLUSIONS: Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

DOI： 10.1016/j.jiac.2024.03.007

Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms. 査読国際誌

Yasuhiro Nakano, Naruhiko Sunada, Kazuki Tokumasu, Hiroyuki Honda, Yuki Otsuka, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Daisuke Omura, Kanako Ochi, Miho Yasuda, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Scientific reports 14 ( 1 ) 5446 - 5446 2024年3月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

DOI： 10.1038/s41598-024-55526-3

【-え、ウソ!実は○○だった!?-"コモンディジーズ"の診断ピットフォール】(Pitfall 23)症状・所見は常に非特異的…!?

大塚勇輝, 大塚文男

総合診療 34 ( 3 ) 298 - 300 2024年3月

先天性心疾患患者の移行期医療:成人循環器医の協力を得る方策成人先天性心疾患の診療の手助けとなる心エコー図検査

武本梨佳, 杜徳尚, 高谷陽一, 中山理絵, 赤木禎治, 中村一文, 笠原真悟, 大塚文男

日本循環器学会学術集会抄録集 88回 CS3 - 4 2024年3月

病院総合診療医には新興感染症に備えた感染症危機管理教育が必要である全国97医療機関の調査より

藤原元嗣, 多胡雅毅, 平田理紗, 香月尚子, 大塚勇輝, 志水太郎, 佐々木陽典, 鋪野紀好, 和足孝之, 高橋宏瑞, 宇根一暢, 内藤俊夫, 大塚文男, 田妻進

日本病院総合診療医学会雑誌 20 ( 臨増1 ) 139 - 139 2024年3月

病院総合診療医には新興感染症に備えた感染症危機管理教育が必要である全国97医療機関の調査より

藤原元嗣, 多胡雅毅, 平田理紗, 香月尚子, 大塚勇輝, 志水太郎, 佐々木陽典, 鋪野紀好, 和足孝之, 高橋宏瑞, 宇根一暢, 内藤俊夫, 大塚文男, 田妻進

日本病院総合診療医学会雑誌 20 ( 臨増1 ) 139 - 139 2024年3月

SARS-CoV-2ワクチン接種後の持続的な副反応の特徴副反応外来における後向き観察研究

徳増一樹, 山下茉奈美, 砂田匠彦, 櫻田泰江, 山本紘一郎, 中野靖浩, 松田祐依, 大塚勇輝, 長谷川徹, 萩谷英大, 本多寛之, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増1 ) 143 - 143 2024年3月

コントロール不十分な糖尿病を伴う全身痛の鑑別プロセスから症状軽快を導けた一例

淺野晃太, 大塚勇輝, 副島佳晃, 川口満理奈, 大國皓平, 本多寛之, 長谷川功, 越智可奈子, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増1 ) 182 - 182 2024年3月

高齢女性の骨折・低カリウム血症を契機にPMAHの診断に至った1例

須山敦仁, 山本紘一郎, 加藤篤之, 副島佳晃, 佐住洋祐, 大國皓平, 中野靖浩, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増1 ) 213 - 213 2024年3月

Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel. 査読国際誌

Wataru Kitamura, Tomohiro Urata, Keiko Fujii, Takuya Fukumi, Kazuhiro Ikeuchi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Transfusion 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

DOI： 10.1111/trf.17765

Penile cavernosal abscess after urethral injury 査読

Koichiro Yamamoto, Hiroyuki Honda, Kou Hasegawa, Hideharu Hagiya, Fumio Otsuka

Clinical Case Reports 12 ( 2 ) 2024年2月

担当区分：最終著者掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Key Clinical Message

We present a patient catheterized for prostatic lesions who developed sepsis of urinary origin with a penile cavernosal abscess due to urethral injury caused by catheter ballooning. Urethral injury might lead to a life‐threatening penile abscess.

DOI： 10.1002/ccr3.8534

Characteristics of Functional Hyperthermia Detected in an Outpatient Clinic for Fever of Unknown Origin. 査読国際誌

Kosuke Oka, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

Journal of Clinical Medicine 13 ( 3 ) 889 2024年2月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index ≥ 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology.

DOI： 10.3390/jcm13030889

【新型コロナ後遺症-これまでの対応と問題点】

大塚勇輝, 徳増一樹, 植田圭吾, 大塚文男

日本医事新報 ( 5208 ) 18 - 27 2024年2月

記述言語：日本語出版者・発行元：(株)日本医事新報社

[1]はじめに・いわゆる「新型コロナ後遺症」にいまだ多くの患者が苦しみ,わが国を含む世界的な社会問題となっている。[2]呼称と定義・「新型コロナ後遺症」などの用語の定義は,医学的には統一されていない。・NIHの「PASC」,WHOの「PCC」という用語には定義が定められ,2023年には診断基準案の提案もなされた。[3]コロナ・アフターケア外来とは・罹患後慢性期にかけての症状の遷延に対し,専門外来であるコロナ・アフターケア(CAC)外来を開設した。・1日1～2人の新規患者を受け入れ,800人以上の患者を対面診療してきた。[4]疫学・CAC外来へは,デルタ株流行時に感染者の約1.5%,オミクロン株では感染者の0.1%程度が受診となった。・CAC外来の受診患者は若干女性が多く,30～50歳代が60%,10歳代など若年者が14%だが,70歳代以上の受診は比較的少ない。・オミクロン株に感染したと思われる症例では,95%の患者で急性期は軽症であったが,後遺症は残っている。[5]症状・症状は多彩であるが,倦怠感・易疲労感が最多で,ブレインフォグは,特にオミクロン株で増加していた。[6]病態とメカニズム・感染後の炎症と免疫応答,自己免疫反応,血栓・血管内皮障害,腸内細菌叢変化,自律神経・内分泌障害,ウイルス残存など,種々の仮説がある。・抑うつ指数,FT4,倦怠感スケール,血中コルチゾール値の間に正の相関がみられる。・捲怠感や味覚・嗅覚障害を随伴する患者では,それぞれ成長ホルモン低値,FT4高値,コルチゾール低値の傾向がある。[7]治療とマネジメント・漢方薬の処方のほか,亜鉛補充,急性期の抗ウイルス薬やメトホルミンの処方にも,一定の効果が認められる。・総合診療的なアプローチで,全人的なケアを心がけている。[8]今後の課題・終診とできるまでに日数を要するほか,対応可能な医師・施設も不足している。(著者抄録)

【入院時から始める退院調整】診療情報提供書の書き方と注意点入院診療とかかりつけ医をつなぐために

大塚勇輝, 川口満理奈, 大塚文男

レジデントノート 25 ( 16 ) 2894 - 2902 2024年2月

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells. 査読国際誌

Yoshiaki Soejima, Nahoko Iwata, Koichiro Yamamoto, Atsuhito Suyama, Yasuhiro Nakano, Fumio Otsuka

International journal of molecular sciences 25 ( 3 ) 2024年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine β-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.

DOI： 10.3390/ijms25031585

Trends in the Incidence of Disseminated Cryptococcosis in Japan: A Nationwide Observational Study, 2015-2021. 査読国際誌

Hidemasa Akazawa, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Mycopathologia 189 ( 1 ) 8 - 8 2024年1月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. METHODS: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). RESULTS: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] - 5.4-27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI - 15.5-10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI - 1.5-8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. CONCLUSION: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required.

DOI： 10.1007/s11046-023-00814-1

Influence of the coronavirus disease 2019 pandemic on the post-graduate career paths of medical students: a cross-sectional study 査読

特集 -"体験型"臨床クイズで習得する!-フィジカル診断エクセレンス -❺内分泌･代謝-10年以上続く原因不明の全身痛

髙瀬了輔, 片岡仁美, 大塚文男

総合診療 34 ( 1 ) 37 - 40 2024年1月

Ayumu Nishimura, Tomoko Miyoshi, Fumio Otsuka, Akihiro Matsukawa

BMC Medical Education 24 ( 1 ) 2024年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Background

The World Health Organization first declared the coronavirus disease 2019 (COVID-19) pandemic in March 2020 and announced the end of the emergency in May 2023. Additionally, the COVID-19 pandemic significantly impacted individuals globally, including medical students. Although the COVID-19 pandemic increased online education, it restricted clinical training, extracurricular activities, and interprovincial travel. Therefore, this study aimed to examine whether the COVID-19 pandemic influenced the choice of training hospitals and career paths among 3rd- to 6th-year medical students in Japan.

Methods

We developed a questionnaire comprising 21 multiple-choice and 1 open-ended questions, which was administered anonymously via online platforms. The survey targeted Japanese medical students to obtain insights into their preferences for training hospitals and career paths during the COVID-19 pandemic. Participants included 4th- to 6th-year medical students from 51 medical schools in Japan. The survey was conducted through student networks from 8 February 2022 to 20 March 2022.

Results

Overall, 507 medical students participated in the survey, with representation from various academic years as follows: 102 (20.1%), 134 (26.4%), 121 (23.9%), and 150 (29.6%) students from the 3rd, 4th, 5th, and 6th year, respectively. Of these, 338 (66.6%) students reported that the COVID-19 pandemic had influenced their choice of training hospitals. The degree of the influence varied based on the university region and the student year. However, most of the students (473, 93.3%) did not change their course for clinical, basic research, or administrative pathways due to the COVID-19 pandemic. Among the clinically oriented students, 391 (77.2%) did not change their preferred speciality.

Conclusions

The COVID-19 pandemic influenced medical students’ choice of training hospitals. Although many students believed that the pandemic would not change their career choices, our results indicate a potential subconscious trend to avoid internal medicine, which is the speciality most directly involved in treating patients with COVID-19.

DOI： 10.1186/s12909-023-05021-6

本邦の小児肥満有病率の10年間の推移 Joinpoint regressionを用いた小児肥満トレンド解析

その他リンク： https://link.springer.com/article/10.1186/s12909-023-05021-6/fulltext.html

A Mediastinum Tumor Presenting With Dysphagia 査読

Koichiro Yamamoto, Fumio Otsuka

JCEM Case Reports 2024年1月

藤原進太郎, 原田洸, 萩谷英大, 小山敏広, 長谷川高誠, 塚原宏一, 大塚文男

日本内分泌学会雑誌 99 ( 4 ) 1052 - 1052 2024年1月

Development of virtual reality educational clips for improving hand hygiene compliance among healthcare providers: a pilot study 査読

Hideharu Hagiya, Shuichi Tanaka, Yuki Otsuka, Fumio Otsuka

Teaching and Learning in Nursing 19 ( 1 ) e17 - e20 2024年1月

COVID-19流行が内分泌検査数に与えた変化査読

大塚勇輝, 古川雅規, 東影明人, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 18 - 21 2024年1月

成人成長ホルモン分泌不全症に関する医療者教育と総合診療科における実践査読

越智可奈子, 徳増一樹, 中野靖浩, 須山敦仁, 副島佳晃, 大塚勇輝, 安田美帆, 小比賀美香子, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 7 - 17 2024年1月

In vitro Activity of Cefmetazole and Flomoxef among Extended-Spectrum Beta-Lactamase producing Enterobacterales. 査読

Koji Iio, Hideharu Hagiya, Tsukasa Higashionna, Fumio Otsuka

New Microbiol. 348 - 353 2024年1月

成人成長ホルモン分泌不全症に関する医療者教育と総合診療科における実践

越智可奈子, 徳増一樹, 中野靖浩, 須山敦仁, 副島佳晃, 大塚勇輝, 安田美帆, 小比賀美香子, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 7 - 17 2024年1月

記述言語：日本語出版者・発行元：(一社)日本病院総合診療医学会

成人成長ホルモン分泌不全症(AGHD)は下垂体前葉機能低下症の中で成長ホルモン(GH)不足により様々な代謝異常をきたす疾患である。治療にはGH製剤の自己注射を要することから,患者の予後改善にはAGHDの早期診断・治療とともに多職種連携や患者教育が重要である。本研究では,AGHD診療における多職種での医療連携や専門医の育成を目的とし,AGHDに関する講義や専攻医に対するAGHD患者のマネジメント指導において,その教育効果を検討した。まず多職種へのAGHD教育実践と効果の検討として,医師・看護師・検査技師・医薬情報担当者・医学生・看護学生・医療技術専門学生(作業療法学科・理学療法学科)に対してAGHDに関する講義を行い,講義前後でAGHDの理解度を評価する目的でアンケートを実施した。アンケート内容を(1)基礎的事項,(2)合併症に関する事項,(3)診断に関する事項,(4)治療・マネジメントに関する事項の4分野に分類して検討したところ,全職種において講義後の正答率が上昇し,各職種の正答率上昇率は分野ごとに違いを認めた。次に,内科専攻医に対してのAGHD診療の実践教育を内科専攻医4名に対して行い,AGHDの新規患者における診断・治療・GH自己注射指導およびマネジメント教育を実施し評価を行った。GH自己注射指導に関しては,自己注射練習用器材を用いて実践的トレーニングを行ったところ,全専攻医において診療能の向上を認めた。AGHD患者の診断やGH自己注射を含めた治療継続においては多職種連携や専門医育成などの医療者教育が非常に重要である。診療においては総合診療科における全人的・総合的診療の一環としての教育実践により,医療者のAGHD診療に対する理解が向上しており教育効果が示された。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J05937&link_issn=&doc_id=20240228380002&doc_link_id=%2Ffg3byoin%2F2024%2F002001%2F003%2F0007-0017%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffg3byoin%2F2024%2F002001%2F003%2F0007-0017%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

COVID-19流行が内分泌検査数に与えた変化

大塚勇輝, 古川雅規, 東影明人, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 18 - 21 2024年1月

記述言語：日本語出版者・発行元：(一社)日本病院総合診療医学会

新型コロナウイルス感染症(COVID-19)の流行に伴い医療へのアクセスが制限されたが,本邦において臨床検査に与えた影響については明らかとなっていない。2017年から2022年までの6年間に岡山大学病院において測定された内分泌検査測定件数を経年的に比較すると,入院・外来ともにCOVID-19禍の3年間ではそれ以前に比してACTH・Cortisol,GH・IGFIの測定件数は増加していた一方で,TSHや遊離T4,Renin活性(PRA)やAldosterone(Aldo)の件数は減少しており,特に外来における変化はTSH(平均値:19173件vs17512件),PRA(322件vs251件),Aldo(472件vs306件)と有意であった。内分泌疾患を有す,或いは疑われる患者に対する対面診療での測定依頼が減ったことや,倦怠感など機能低下で生じうる症状を呈する患者が増えたことがその要因ではないかと考察された。COVID-19の流行が少なくとも部分的に本邦での医療の質に影響を与えた可能性が示唆され,その要因分析が今後の課題と思われた。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J05937&link_issn=&doc_id=20240228380003&doc_link_id=%2Ffg3byoin%2F2024%2F002001%2F004%2F0018-0021%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffg3byoin%2F2024%2F002001%2F004%2F0018-0021%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Changes in the place of death before and during the COVID-19 pandemic in Japan. 査読国際誌

Masashi Shibata, Yuki Otsuka, Hideharu Hagiya, Toshihiro Koyama, Hideyuki Kashiwagi, Fumio Otsuka

PloS one 19 ( 2 ) e0299700 2024年

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan. METHODS: This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death. RESULTS: After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0-19 age group, while hospital deaths decreased in the 20-64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by -4.0% (95% CI: -4.9 to -3.1) in 2019-2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively. CONCLUSION: PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age.

DOI： 10.1371/journal.pone.0299700

シリーズ「一目瞭然！目で診る症例」問題編

中本健太, 萩谷英大, 林瑠衣子, 大塚文男

日本内科学会雑誌 113 127 - 130 2024年

「新型コロナウイルス感染症罹患後症状における睡眠障害の特徴と推移」査読

大塚文男, 砂田匠彦, 大塚勇輝, 徳増一樹, 本多寛之, 古川雅規

日本病院総合診療医学会雑誌 20(3) 129 - 134 2024年

Functional interaction of Clock genes and bone morphogenetic proteins in the adrenal cortex. 査読国際誌

Yoshiaki Soejima, Koichiro Yamamoto, Yasuhiro Nakano, Atsuhito Suyama, Nahoko Iwata, Fumio Otsuka

Vitamins and hormones 124 429 - 447 2024年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The bone morphogenetic protein (BMP) system in the adrenal cortex plays modulatory roles in the control of adrenocortical steroidogenesis. BMP-6 enhances aldosterone production by modulating angiotensin (Ang) II-mitogen-activated protein kinase (MAPK) signaling, whereas activin regulates the adrenocorticotropin (ACTH)-cAMP cascade in adrenocortical cells. A peripheral clock system in the adrenal cortex was discovered and it has been shown to have functional roles in the adjustment of adrenocortical steroidogenesis by interacting with the BMP system. It was found that follistatin, a binding protein of activin, increased Clock mRNA levels, indicating an endogenous function of activin in the regulation of Clock mRNA expression. Elucidation of the interrelationships among the circadian clock system, the BMP system and adrenocortical steroidogenesis regulated by the hypothalamic-pituitary-adrenal (HPA) axis would lead to an understanding of the pathophysiology of adrenal disorders and metabolic disorders and the establishment of better medical treatment from the viewpoint of pharmacokinetics.

DOI： 10.1016/bs.vh.2023.05.002

Trends of correlations between serum levels of growth hormone and insulin-like growth factor-I in general practice. 査読国際誌

Kohei Oguni, Koichiro Yamamoto, Yasuhiro Nakano, Yoshiaki Soejima, Atsuhito Suyama, Ryosuke Takase, Miho Yasuda, Kou Hasegawa, Fumio Otsuka

Frontiers in endocrinology 15 1381083 - 1381083 2024年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly (R=0.50; P<0.001) and patients with GHD (R=0.39; P=0.08), a negative correlation was found in the NGRD group (R=-0.23; P<0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL (R=-0.45; P<0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids (R=-0.51; P<0.001 and R=-0.59; P<0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions.

DOI： 10.3389/fendo.2024.1381083

What is the Definition of General Medicine and Generalists in Japan? [Letter]. 査読国際誌

Yuya Yokota, Yuki Otsuka, Fumio Otsuka

International journal of general medicine 17 3465 - 3466 2024年

Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan. 査読国際誌

Satoru Morita, Kazuki Tokumasu, Yuki Otsuka, Hiroyuki Honda, Yasuhiro Nakano, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Yoshiaki Soejima, Keigo Ueda, Fumio Otsuka

PloS one 19 ( 12 ) e0315385 2024年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) related to COVID-19 have remained uncertain. To elucidate the clinical trend of ME/CFS induced by long COVID, we examined data for patients who visited our outpatient clinic established in a university hospital during the period from Feb 2021 to July 2023. METHODS: Long COVID patients were classified into two groups, an ME/CFS group and a non-ME/CFS group, based on three diagnostic criteria. RESULTS: The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations. The frequency of ME/CFS decreased from 23.9% in the Preceding period to 13.7% in the Delta-dominant period and to 3.3% in the Omicron-dominant period. Fatigue and headache were commonly frequent complaints in the ME/CFS group, and the frequency of poor concentration in the ME/CFS group was higher in the Omicron period. Serum ferritin levels were significantly higher in female patients in the ME/CFS group infected in the Preceding period. In the ME/CFS group, the proportion of patients complaining of brain fog significantly increased from 22.2% in the Preceding period to 47.9% in the Delta period and to 81.3% in the Omicron period. The percentage of patients who had received vaccination was lower in the ME/CFS group than the non-ME/CFS group over the study period, whereas there were no differences in the vaccination rate between the groups in each period. CONCLUSION: The proportion of long COVID patients who developed ME/CFS strictly diagnosed by three criteria was lower among patients infected in the Omicron phase than among patients infected in the other phases, while the proportion of patients with brain fog inversely increased. Attention should be paid to the variant-dependent trends of ME/CFS triggered by long COVID (300 words).

DOI： 10.1371/journal.pone.0315385

Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021. 査読国際誌

Shintaro Fujiwara, Ko Harada, Hideharu Hagiya, Toshihiro Koyama, Kosei Hasegawa, Hirokazu Tsukahara, Fumio Otsuka

Clinical obesity e12636 2023年12月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6-8, 9-11, and 12-14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%-4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%-4.0%) and 9- to 11-year (0.9%-2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%-8.9%) and girls of many age groups (2.6%-8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary.

DOI： 10.1111/cob.12636

The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study 査読

Taku Murakami, Akira Yamamoto, Hideharu Hagiya, Mikako Obika, Yasuhiro Mandai, Tomoko Miyoshi, Hitomi Kataoka, Fumio Otsuka

BMC Medical Education 23 ( 1 ) 2023年11月

担当区分：最終著者掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Background

Simulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties.

Methods

This study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents’ medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups.

Results

A total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation.

Conclusion

Simulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties.

DOI： 10.1186/s12909-023-04798-w

Characteristics of Persistent Symptoms Manifested after SARS-CoV-2 Vaccination: An Observational Retrospective Study in a Specialized Clinic for Vaccination-Related Adverse Events 査読

その他リンク： https://link.springer.com/article/10.1186/s12909-023-04798-w/fulltext.html

Kazuki Tokumasu, Manami Fujita-Yamashita, Naruhiko Sunada, Yasue Sakurada, Koichiro Yamamoto, Yasuhiro Nakano, Yui Matsuda, Yuki Otsuka, Toru Hasegawa, Hideharu Hagiya, Hiroyuki Honda, Fumio Otsuka

Vaccines 11 ( 11 ) 1661 - 1661 2023年10月

担当区分：最終著者掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31–64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment.

DOI： 10.3390/vaccines11111661

Recognition and Practice of Hypopituitarism After Traumatic Brain Injury and Subarachnoid Hemorrhage in Japan: A Survey. 査読国際誌

Shigeyuki Tahara, Fumio Otsuka, Takaaki Endo

Neurology and therapy 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Individuals with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH) are at a high risk of hypopituitarism, and should benefit from early diagnosis and management. However, data on awareness, attitudes, and practices of physicians treating hypopituitarism post-TBI/SAH are limited. The objectives of this study were to gain an understanding of the awareness of Japanese neurosurgeons and endocrinologists towards hypopituitarism post-TBI/SAH and the need for pituitary function assessments in these patients; and to assess the practices and perspectives of these specialists on screening patients with this condition. METHODS: An observational, cross-sectional study was performed that included a Web-based survey of practicing neurosurgeons managing ≥ 1 new patients with TBI/SAH per year or endocrinologists with ≥ 1 new patients per year with a history of TBI/SAH. RESULTS: Of the 316 respondents (201 neurosurgeons [male, 95.5%]; 115 endocrinologists [male, 77.4%]), 75.6% of neurosurgeons and 81.7% of endocrinologists were aware of the probable occurrence of hypopituitarism post-TBI/SAH, and 79% neurosurgeons and 93.8% endocrinologists considered pituitary function impairment after TBI/SAH to be either very important or important. Hypopituitarism after TBI/SAH was recognized as an important concern by both neurosurgeons (79%) and endocrinologists (93.8%). Although many respondents agreed that such patients remain undiagnosed and untreated, pituitary function assessment post-TBI/SAH has only been performed to a limited extent. The awareness that post-TBI/SAH hypopituitarism is often transient and can progress over several weeks or months was lower in neurosurgeons (46.8%) than in endocrinologists (66.1%). CONCLUSIONS: The level of awareness of hypopituitarism post-TBI/SAH was lower among Japanese neurosurgeons than among endocrinologists. Educational programs and detailed guidance for the diagnosis and treatment of hypopituitarism post-TBI/SAH are warranted.

DOI： 10.1007/s40120-023-00553-x

Relevance of complement immunity with brain fog in patients with long COVID. 査読国際誌

Hideharu Hagiya, Kazuki Tokumasu, Yuki Otsuka, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Masanori Furukawa, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2023年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50). METHODS: This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors. RESULTS: Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66). CONCLUSIONS: High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.

DOI： 10.1016/j.jiac.2023.10.016

Evaluating the efficiency and safety of large-volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study. 査読国際誌

Yuichi Sumii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Transfusion 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS: Although pre-apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/μL, p < .001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL.

DOI： 10.1111/trf.17563

LETTER TO EDITOR: In the midst of a pandemic, significant event analysis may protect the well-being of healthcare professionals. 査読

Tomoko Miyoshi, Mikiko Iwatani and Fumio Otsuka

8 ( 4 ) 2023年10月

Safety and usefulness of nebulized liposomal amphotericin B: Systematic scoping review. 査読国際誌

Hideharu Hagiya, Yoshito Nishimura, Fumio Otsuka

Pulmonary pharmacology & therapeutics 82 102233 - 102233 2023年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy. METHODS: According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022. RESULTS: Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed. CONCLUSION: In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.

DOI： 10.1016/j.pupt.2023.102233

Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan. 査読

Miho Ando, Yoshihisa Hanayama, Yoshito Nishimura, Hideharu Hagiya, Fumio Otsuka

Acta medica Okayama 77 ( 5 ) 527 - 536 2023年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

DOI： 10.18926/AMO/65975

Hypertension is the only clue for the discovery of adrenal rhabdomyosarcoma 査読

一過性に口渇・多尿を生じた心因性多飲の1例

副島佳晃, 大塚勇輝, 川口満里奈, 大國皓平, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 99 ( 2 ) 592 - 592 2023年10月

Koichiro Yamamoto, Fumio Otsuka

Hypertension Research 2023年9月

Epidemiological Characteristics and Trends in the Incidence of Leptospirosis in Japan: A Nationwide, Observational Study from 2006 to 2021. 査読国際誌

Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

The American journal of tropical medicine and hygiene 109 ( 3 ) 589 - 594 2023年9月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

During this age of climate change, the incidence of tropical diseases may change. This study compared the epidemiological characteristics and trends of leptospirosis in Japan between the endemic region, Okinawa, and the rest of the country. Infectious Diseases Weekly Reports were used to determine the numbers and crude incidence rates of leptospirosis. Data were stratified by sex, age, the estimated location of the infection, the notified regions, and the reporting month. A joinpoint regression analysis was performed to estimate the annual percentage change (APC). During the 16-year study period (2006-2021), 543 leptospirosis cases were reported, with male dominance (86.2%). Approximately half of these cases were reported from Okinawa (47.1%). The patients were relatively younger in Okinawa (20-29 years, 23.4%; 30-39 years, 20.7%) than outside Okinawa. The frequency of imported cases was significantly higher outside Okinawa (0.4% versus 14.3%). The incidences of leptospirosis in and outside Okinawa were apparently higher during the summer and typhoon seasons. The annual crude incidence ratios were 20-200 times higher in Okinawa than in the rest of the country. The average APCs for the entire study period in Okinawa and the rest of Japan were 1.6% (95% CI: -5.9 to 9.6) and -1.8% (95% CI: -7.8 to 4.6), respectively, without any particular trends. Collectively, the patient profile of leptospirosis differed between Okinawa (younger men) and outside Okinawa (middle- or older-aged men with a history of traveling abroad). The disease remains a neglected tropical disease; continuous surveillance with close monitoring is required.

DOI： 10.4269/ajtmh.23-0131

Case Report: Leptospirosis after a Typhoon Disaster Outside the Endemic Region, Japan. 査読国際誌

Yukichika Yamamoto, Hideharu Hagiya, Ruiko Hayashi, Fumio Otsuka

The American journal of tropical medicine and hygiene 109 ( 3 ) 587 - 588 2023年9月

担当区分：最終著者記述言語：英語

Leptospirosis is a zoonotic disease that primarily affects people in tropical and subtropical areas worldwide. Owing to the temperate climate of Japan, leptospirosis is not endemic across the country. Domestic cases of leptospirosis have been mainly reported in Okinawa and the southwestern subtropical islands, but not in the other regions. Here, we describe a case of leptospirosis that developed and was diagnosed outside the domestically endemic region. Notably, disease onset occurred shortly after the patient experienced a flood after a typhoon disaster. With global warming, the international prevalence of leptospirosis may change. Physicians outside currently endemic areas must be aware of this tropical disease.

DOI： 10.4269/ajtmh.23-0133

Task shifting of medical office works: A preliminary questionnaire survey for generalists. 査読

Yuki Otsuka, Hideharu Hagiya, Naruhiko Sunada, Fumio Otsuka

Journal of general and family medicine 24 ( 5 ) 317 - 319 2023年9月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

To reduce physician burden, task shifting of clerical work from physicians to medical assistants is being promoted; however, it depends on hospitals. A questionnaire survey was conducted among 40 general physicians at Okayama University Hospital in December 2022 to investigate physicians' preferences toward task shifting. Compared to other tasks, most physicians thought that ordering examinations (14, 47%), replying to referral letters (19, 63%), and prescriptions (21, 70%) and medical record entries (22, 73%) should not be task shifted. Physicians' controversial opinions on task shifting maybe the reason behind the slow progress in task shifting.

DOI： 10.1002/jgf2.641

Increased evidence for no benefit of contact precautions in preventing extended-spectrum β-lactamases-producing Enterobacteriaceae: Systematic scoping review 査読

Hideharu Hagiya, Fumio Otsuka

American Journal of Infection Control 51 ( 9 ) 1056 - 1062 2023年9月

Super acute-onset disseminated BCG infection: A case report. 査読国際誌

Ryosuke Takase, Hideharu Hagiya, Takumi Fujimori, Yukika Yokoyama, Koji Iio, Hiroyuki Honda, Kou Hasegawa, Fumio Otsuka

Journal of infection and chemotherapy 29 ( 9 ) 919 - 921 2023年9月

担当区分：最終著者記述言語：英語

Intravesical Bacillus Calmette-Guérin (BCG) instillation is an established immunotherapy for superficial bladder cancer. Herein, we describe a case of disseminated BCG infection that developed immediately after the first BCG injection. A 76-year-old man diagnosed with non-invasive bladder cancer underwent intravesical BCG instillation; he developed high fever and systemic arthralgia later that night. General examination did not reveal any infectious sources, and a combination therapy of isoniazid, rifabutin, and ethambutol was initiated after collecting his blood, urine, bone marrow, and liver biopsy samples for mycobacterial cultures. Three weeks later, Mycobacterium bovis was detected in the urine and bone marrow samples, and pathological investigation of liver biopsy revealed multiple small epithelial granulomas with focal multinucleated giant cells, leading to a diagnosis of disseminated BCG infection. The patient recovered after long-term antimycobacterial therapy without remarkable sequelae. Most cases of disseminated BCG infection occur after several doses of BCG injections, and its onset reportedly varies among cases, ranging from a few days to several months. The present case was notable as disease onset was observed only a few hours after the first BCG injection. Although rare, development of disseminated BCG infection should be considered as a differential diagnosis in patients at any time after intravesical BCG instillation therapy.

DOI： 10.1016/j.jiac.2023.05.017

Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells 査読

Yoshiaki Soejima, Nahoko Iwata, Ran Nishioka, Mako Honda, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Fumio Otsuka

International Journal of Molecular Sciences 24 ( 16 ) 12559 - 12559 2023年8月

担当区分：最終著者,　責任著者掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis.

DOI： 10.3390/ijms241612559

Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients. 査読

Masaya Iwamuro, Takumi Kondo, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Takahide Takahashi, Araki Hirabata, Takehiro Tanaka, Fumio Otsuka, Yoshinobu Maeda, Hiroyuki Okada

Acta medica Okayama 77 ( 4 ) 347 - 357 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry.

DOI： 10.18926/AMO/65740

Preoperative detection of functional somatostatin receptors in a patient with an insulinoma. 査読国際誌

Kohei Oguni, Shinnosuke Fukushima, Yukichika Yamamoto, Kou Hasegawa, Hideharu Hagiya, Naoko Inoshita, Fumio Otsuka

Clinical case reports 11 ( 8 ) e7771 2023年8月

担当区分：最終著者記述言語：英語

Octreotide is used in patients with insulinomas to treat hypoglycemia, and somatostatin receptor (SSTR) 2 expression is important for its efficacy. We report a case of insulinoma in a 50-year-old woman that responded to an octreotide test, showed accumulation in somatostatin scintigraphy, and was positive for SSTR2A on immunostaining.

DOI： 10.1002/ccr3.7771

COVID-19罹患を契機に発症したリウマチ性多発筋痛症の一例

高木桃李, 大塚勇輝, 副島佳晃, 川口満理奈, 大國皓平, 徳増一樹, 長谷川功, 本多寛之, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 166 - 166 2023年8月

Covid-19流行時の予防、診療、感染制御に貢献する病院総合診療医～全国97の総合診療部門の解析

香月尚子, 多胡雅毅, 平田理紗, 大塚勇輝, 志水太郎, 佐々木陽典, 鋪野紀好, 和足孝之, 高橋宏端, 宇根一暢, 内藤俊夫, 大塚文男, 田妻進

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 169 - 169 2023年8月

褥瘡を伴う胸髄損傷患者に発症した腰部化膿性脊椎炎の1例

森田悟, 加藤篤之, 須山敦仁, 佐藤啓介, 佐住洋祐, 大塚勇輝, 大國皓平, 大野洋平, 長谷川功, 本多寛之, 萩谷英大, 小田孔明, 今村竜太, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 180 - 180 2023年8月

自動車運転中の失神・交通事故の原因精査に詳細な血糖測定が有用であった一例

佐藤啓介, 高瀬了輔, 森田悟, 加藤篤之, 須山敦仁, 佐住洋祐, 大塚勇輝, 大國皓平, 長谷川功, 本多寛之, 小比賀美香子, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 181 - 181 2023年8月

当院総合内科・総合診療科における後腹膜線維症49症例の特徴の検討

花山宜久, 安藤美穂, 西村義人, 徳増一樹, 長谷川功, 萩谷英大, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 163 - 163 2023年8月

Covid-19流行時の予防、診療、感染制御に貢献する病院総合診療医～全国97の総合診療部門の解析

香月尚子, 多胡雅毅, 平田理紗, 大塚勇輝, 志水太郎, 佐々木陽典, 鋪野紀好, 和足孝之, 高橋宏瑞, 宇根一暢, 内藤俊夫, 大塚文男, 田妻進

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 169 - 169 2023年8月

眼内炎診療における病院総合医の役割

川口満理奈, 大塚勇輝, 副島佳晃, 安藤航, 高木桃李, 大國皓平, 長谷川功, 本多寛之, 萩谷英大, 小比賀美香子, 森田哲郎, 森實祐基, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 142 - 142 2023年8月

病初期より関節リウマチの臨床像も有したリウマチ性多発筋痛症の一例

安藤航, 大塚勇輝, 副島佳晃, 川口満理奈, 大國皓平, 本多寛之, 長谷川功, 花山宜久, 勝山隆行, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 150 - 150 2023年8月

MOCA-Jを用いたCOVID-19罹患後症状のブレインフォグの臨床的特徴の解明

長谷川徹, 大塚勇輝, 櫻田泰江, 徳増一樹, 砂田匠彦, 小西隆之, 中野靖浩, 本多寛之, 萩谷英大, 小比賀美香子, 植田圭吾, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 168 - 168 2023年8月

病初期より関節リウマチの臨床像も有したリウマチ性多発筋痛症の一例

安藤航, 大塚勇輝, 副島佳晃, 川口満理奈, 大國皓平, 本多寛之, 長谷川功, 花山宜久, 勝山隆行, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 150 - 150 2023年8月

眼内炎診療における病院総合医の役割

川口満理奈, 大塚勇輝, 副島佳晃, 安藤航, 高木桃李, 大國皓平, 長谷川功, 本多寛之, 萩谷英大, 小比賀美香子, 森田哲郎, 森實祐基, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 142 - 142 2023年8月

自動車運転中の失神・交通事故の原因精査に詳細な血糖測定が有用であった一例

佐藤啓介, 高瀬了輔, 森田悟, 加藤篤之, 須山敦仁, 佐住洋祐, 大塚勇輝, 大國皓平, 長谷川功, 本多寛之, 小比賀美香子, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 181 - 181 2023年8月

就学患者のCOVID-19罹患後症状とその社会的影響

櫻田泰江, 大塚勇輝, 徳増一樹, 砂田匠彦, 本多寛之, 中野靖浩, 松田祐依, 萩谷英大, 植田圭吾, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 168 - 168 2023年8月

褥瘡を伴う胸髄損傷患者に発症した腰部化膿性脊椎炎の1例

森田悟, 加藤篤之, 須山敦仁, 佐藤啓介, 佐住洋祐, 大塚勇輝, 大國皓平, 大野洋平, 長谷川功, 本多寛之, 萩谷英大, 小田孔明, 今村竜太, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 180 - 180 2023年8月

COVID-19罹患を契機に発症したリウマチ性多発筋痛症の一例

高木桃李, 大塚勇輝, 副島佳晃, 川口満理奈, 大國皓平, 徳増一樹, 長谷川功, 本多寛之, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 166 - 166 2023年8月

当院総合内科・総合診療科における後腹膜線維症49症例の特徴の検討

花山宜久, 安藤美穂, 西村義人, 徳増一樹, 長谷川功, 萩谷英大, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 163 - 163 2023年8月

不明熱診療にて遭遇した機能性高体温症とその臨床的特徴

岡浩介, 徳増一樹, 萩谷英大, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増2 ) 145 - 145 2023年8月

Phase-dependent trends of male hypogonadism in long COVID patients. 査読

Naruhiko Sunada, Yuki Otsuka, Hiroyuki Honda, Kazuki Tokumasu, Fumio Otsuka

Endocrine journal 70 ( 7 ) 755 - 756 2023年7月

Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID. 査読国際誌

Yukichika Yamamoto, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Toru Hasegawa, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine 12 ( 14 ) 2023年7月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. METHODS: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. RESULTS: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8-353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4-251.5) and no-fatigue group (86.7 μg/L, 37.5-209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05). CONCLUSIONS: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients.

DOI： 10.3390/jcm12144737

Angioedema‐like eyelid edema following the second NVX‐CoV2373 COVID‐19 vaccination 査読

Mari Matsumoto, Yoshio Kawakami, Tomoko Miyake, Yoji Hirai, Hitomi Kataoka, Fumio Otsuka, Shin Morizane

Journal of Cutaneous Immunology and Allergy 6 ( 5 ) 194 - 195 2023年7月

A Case of Typhoid Fever Presenting with Non-G6PD Associated Hemolytic Anemia 査読

Shinnosuke Fukushima, Hideharu Hagiya, Hiroyuki Honda, Tomoharu Ishida, Kou Hasegawa, Fumio Otsuka

Journal of Travel Medicine 2023年7月

担当区分：最終著者掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Typhoid fever is one of the representative febrile diseases in tropical and subtropical countries with poor hygiene. Among the anaemic conditions involving patients with typhoid fever, autoimmune hemolytic anaemia would be one of the potential causes in the absence of G6PD deficiency or intestinal haemorrhage

DOI： 10.1093/jtm/taad092

Endogenous panophthalmitis after colonoscopy 査読

Yukichika Yamamoto, Kohei Oguni, Hideharu Hagiya, Fumio Otuska

Internal and Emergency Medicine 2023年7月

Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicenter randomized controlled clinical trial. 査読国際誌

Shu Okugawa, Mahoko Ikeda, Kosuke Kashiwabara, Takashi Moritoyo, Takao Kohsaka, Toshio Shimizu, Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka, Ayumi Miwa, Nobuhito Kisimoto, Ayako Mizoguchi, Akira Imamura, Kazuhiko Ikeuchi, Takeya Tsutsumi, Daisuke Jubishi, Hideki Hashimoto, Koh Okamoto, Sohei Harada, Jun-Ichiro Inoue, Yasuyuki Seto, Kyoji Moriya

International journal of antimicrobial agents 62 ( 3 ) 106922 - 106922 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19). METHODS: In this exploratory multicenter randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6. RESULTS: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; p=0.022). Serious adverse events were not observed in either group. Phlebitis occurred in approximately 50% of patients treated with nafamostat. CONCLUSIONS: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

DOI： 10.1016/j.ijantimicag.2023.106922

臨床実習前医学生におけるゾーニング実習の実践

越智可奈子, 萩谷英大, 小崎吉訓, 三好智子, 山下範之, 伊野英男, 成瀬恵治, 大塚文男, 松川昭博

医学教育 54 ( Suppl. ) 296 - 296 2023年7月

成人成長ホルモン分泌不全症における医療者教育実践に関する検討

越智可奈子, 徳増一樹, 大塚勇輝, 中野靖浩, 小比賀美香子, 大塚文男

医学教育 54 ( Suppl. ) 296 - 296 2023年7月

Acute arthritis caused by sarcoidosis. 査読

Rio Ogami, Yuki Otsuka, Kou Hasegawa, Kazuki Tokumasu, Mikako Obika, Masanori Fujii, Fumio Otsuka

Journal of general and family medicine 24 ( 4 ) 264 - 265 2023年7月

担当区分：最終著者記述言語：英語

Here we report a case of sarcoidosis which demonstrated with bilateral ankle arthritis. We usually do not consider sarcoidosis routinely for the differential diagnosis of acute arthritis, however, up to 15 to 25% of sarcoidosis complicate arthritis, typically in ankle joints. Sarcoid arthritis is reported to occur mainly in young northern Europe women, whereas this case intimate that we should take sarcoidosis into account as the differential diagnosis of ankle arthralgia also among Asian men especially when combining upper respiratory symptoms.

DOI： 10.1002/jgf2.621

大学病院総合内科・総合診療科における臨床実習教育の学生視点の気づきとは質的研究

四肢と左臀部に皮下硬結を形成したExtensive Subcutaneous Sarcoidosisの1例

臼井真菜, 杉原悟, 立花宏太, 川上佳夫, 森実真, 中本健太, 大塚文男

日本皮膚科学会雑誌 133 ( 8 ) 1889 - 1889 2023年7月

山本幸近, 徳増一樹, 大塚文男

医学教育 54 ( Suppl. ) 205 - 205 2023年7月

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch 査読

Takumi Kondo, Keiko Fujii, Nobuharu Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 2023年6月

Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021. 査読

Shinnosuke Fukushima, Hideharu Hagiya, Kazuhiro Uda, Kazuyoshi Gotoh, Fumio Otsuka

Acta medica Okayama 77 ( 3 ) 255 - 262 2023年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama.

DOI： 10.18926/AMO/65490

Endocrinological Changes after Anamorelin Administration in Patients with Gastrointestinal Cancer. 査読

Sakiko Kuraoka, Masaya Iwamuro, Takuya Satomi, Tatsuhiro Yamazaki, Kenta Hamada, Yoshiyasu Kono, Hiromitsu Kanzaki, Hironari Kato, Fumio Otsuka, Hiroyuki Okada

Acta Medica Okayama 77 ( 3 ) 235 - 241 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Changes in hormone levels in patients with cancer cachexia after anamorelin administration have not been fully investigated. This study aimed to determine how anamorelin affects the endocrine system in patients with gastrointestinal cancer and cachexia. We prospectively enrolled 13 patients and comprehensively investigated their body weight and levels of serum albumin, hemoglobin A1c (HbA1c), and hormones before (week 0) and 3 and 12 weeks after anamorelin administration. The variables were evaluated at week 3 in 9 patients and at week 12 in 5 patients. At week 3, anamorelin administration resulted in body weight gain and increased the levels of growth hormone and HbA1c, as well as insulin-like growth factor-1 standard deviation scores (IGF-1 SD scores). At the same time, negative correlations were observed between ΔIGF-1 SD score and Δthyroidstimulating hormone (TSH) and between ΔIGF-1 SD score and Δfree testosterone. ΔBody weight and ΔIGF-1 SD score correlated positively at week 12. These results suggest that TSH and free testosterone levels can be affected 3 weeks after anamorelin administration; however, those variables tend to return to a state of equilibrium, and anabolic effects of anamorelin appear in long-term (≥ 12 weeks) users.

DOI： 10.18926/AMO/65488

最先端医療の今内分泌視点から捉えたCOVID-19罹患後の倦怠感の機序とその解明

大塚勇輝, 徳増一樹, 大塚文男

Medical Science Digest 49 ( 7 ) 385 - 387 2023年6月

記述言語：日本語出版者・発行元：(株)ニュー・サイエンス社

新型コロナウイルス感染症(COVID-19)罹患後症状(Post COVID-19 Condition:PCC)に悩む患者が多く存在し社会的問題となっている中で,その最多症状である「全身倦怠感」は鑑別すべき疾患も多く検査での可視化も難しい。一方でPCCに伴う倦怠感の重症度は症例によって大きく異なっており,倦怠感の客観的評価や予後予測に有用な指標を見出すことがPCC診療と研究における課題である。我々は2021年2月にいち早くPCCの専門外来であるコロナ・アフターケア外来を開設し多数のPCC患者の診療を行ってきた。そこで得られたデータをもとに科学研究費の助成も受けてPCCにおける倦怠感を内分泌の視点から考察を試み世界に向けた発信を目指しているところである。本稿ではそうした我々の取組みと得られつつある知見について概説する。(著者抄録)

Manifestation of Headache Affecting Quality of Life in Long COVID Patients. 査読国際誌

Kana Fujita, Yuki Otsuka, Naruhiko Sunada, Hiroyuki Honda, Kazuki Tokumasu, Yasuhiro Nakano, Yasue Sakurada, Mikako Obika, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine 12 ( 10 ) 2023年5月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID.

DOI： 10.3390/jcm12103533

【医師の書類作成はじめの一歩診療情報提供書、診断書から院内の記録まで、効率的な"伝わる書類"の書きかた】電子カルテ時代の診療記録への心構え

Furious lung abscess due to Parvimonas micra 査読

Shinnosuke Fukushima, Hideharu Hagiya, Hiromichi Naito, Fumio Otsuka

Respirology Case Reports 11 ( 6 ) 2023年5月

Stimulatory effects of vasopressin on progesterone production and BMP signaling by ovarian granulosa cells 査読

Koichiro Yamamoto, Yasuhiro Nakano, Nahoko Iwata, Yoshiaki Soejima, Atsuhito Suyama, Toru Hasegawa, Fumio Otsuka

Biochemical and Biophysical Research Communications 2023年5月

大塚勇輝, 大塚文男

レジデントノート 25 ( 3 ) 420 - 424 2023年5月

Susceptibility of ceftolozane/tazobactam against multidrug-resistant and carbapenem-resistant Pseudomonas aeruginosa. 査読国際誌

Ayaka Kakehi, Hideharu Hagiya, Koji Iio, Takumi Fujimori, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

The new microbiologica 46 ( 2 ) 213 - 215 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Ceftolozane (CTLZ) is a novel cephalosporin antibiotic that exhibits broad-spectrum activity against gram-negative pathogens, including Pseudomonas aeruginosa, especially when combined with tazobactam (TAZ). We examined the minimum inhibitory concentration (MIC) of CTLZ/TAZ for 21 multidrug-resistant P. aeruginosa (MDRP) and eight carbapenem-resistant P. aeruginosa (CRPA) strains isolated at Okayama University Hospital, Japan. Consequently, 81% (17/21) of the MDRP strains and 25% (2/8) of the CRPA strains were resistant to CTLZ/TAZ (MIC >8 μg/mL). All 18 blaIMP-positive strains showed resistance to CTLZ/TAZ, whereas the drug retained in vitro susceptibility in 54.5% (6/11 strains) of blaIMP-negative strains.

多発骨折を契機に発見され、社会的介入を要したビタミンD欠乏の1例

須山敦仁, 大塚勇輝, 中野靖浩, 松田祐依, 櫻田泰江, 小比賀美香子, 豊川達也, 大塚文男

日本内分泌学会雑誌 99 ( 1 ) 389 - 389 2023年5月

後縦靱帯骨化症を合併し椎弓切除術を要した成人XLHの1例

山本紘一郎, 本多寛之, 大國皓平, 中野靖浩, 徳増一樹, 長谷川功, 長谷川高誠, 安原隆雄, 大塚文男

日本内分泌学会雑誌 99 ( 1 ) 330 - 330 2023年5月

新型コロナウイルス後遺症診療において発見された内分泌代謝疾患

中野靖浩, 副島佳晃, 田中秀一, 大塚勇輝, 徳増一樹, 本多寛之, 長谷川功, 萩谷英大, 大塚文男

日本内分泌学会雑誌 99 ( 1 ) 323 - 323 2023年5月

Case Series of Granulicatella Bacteremia: A Single-centered, Five-year Retrospective Study. 査読

Shinnosuke Fukushima, Hideharu Hagiya, Koji Iio, Hiroyuki Honda, Tomoharu Ishida, Hirokazu Nagaoka, Kou Hasegawa, Fumio Otsuka

Acta medica Okayama 77 ( 2 ) 203 - 207 2023年4月

担当区分：最終著者記述言語：英語

Granulicatella species are rare, nutritionally variant streptococci that cause infective endocarditis. Their clinical and microbiological characteristics remain unknown. We reviewed five years of Granulicatella cases in our hospital database (Jan 2017-Jun 2022), finding 6 Granulicatella adiacens cases and 1 Granulicatella elegans case. Clinical backgrounds and bacteremia sources were diverse; 3 cases developed polymicrobial bacteremia. Antimicrobial testing showed non-susceptibility to penicillin G in 4 of 7 cases (57.1%), and high susceptibility to carbapenems and vancomycin in all cases. Determining optimal antibiotic therapy for Granulicatella infections is vital in this era of antimicrobial resistance.

DOI： 10.18926/AMO/65151

四肢と左臀部に生じたextensive subcutaneous sarcoidosisの1例

臼井真菜, 杉原悟, 立花宏太, 安富陽平, 川上佳夫, 中本健太, 大塚文男, 森実真

西日本皮膚科 85 ( 2 ) 109 - 112 2023年4月

記述言語：日本語出版者・発行元：日本皮膚科学会-西部支部

71歳,女性。1年前に右膝と両側前腕に皮下硬結を自覚し,その後左臀部にも皮下硬結が出現した。右膝に20×10cm,左臀部に10×7cm,右前腕に10×7cm,左前腕に2個の7×5cmの板状皮下硬結がみられた。皮膚生検では皮下脂肪組織に非乾酪壊死性類上皮細胞肉芽腫を認め,sIL-2Rは1697.0U/mlと高値であった。胸部CTでは縦隔リンパ節の軽度腫大があり,Gaシンチグラフィーでは四肢と左臀部の皮下硬結部に高度な集積を認め,extensive subcutaneous sarcoidosisと診断した。膝関節屈曲制限が生じる懸念があったためプレドニゾロン25mg/day内服を開始したところ,皮下病変は速やかに縮小し,sIL-2Rは418.3U/mlまで低下した。皮下型サルコイドーシスではトラニラストやミノサイクリン内服で軽快する症例や,無治療で軽快する症例もあるが,本症例では,右膝部皮下病変の拡大による歩行障害が懸念されたため,ステロイド内服による治療を選択した。広範な皮下型病変を呈するサルコイドーシスでは,sIL-2Rや皮膚病変のサイズなどを総合的に評価し,病勢を検討することが必要である。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01003&link_issn=&doc_id=20230516250006&doc_link_id=10.2336%2Fnishinihonhifu.85.109&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.85.109&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients. 査読国際誌

Yui Matsuda, Kazuki Tokumasu, Yuki Otsuka, Naruhiko Sunada, Hiroyuki Honda, Yasue Sakurada, Yasuhiro Nakano, Toru Hasegawa, Mikako Obika, Keigo Ueda, Fumio Otsuka

Journal of clinical medicine 12 ( 5 ) 2023年3月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. METHODS: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 μg/dL (10.7 μmol/L) were compared with characteristics of patients with normozincemia. RESULTS: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = -0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 μg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. CONCLUSIONS: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.

DOI： 10.3390/jcm12052062

ペースメーカ留置を回避出来た粘液水腫性昏睡による洞不全症候群の1例

長谷川功, 原田洸, 山本紘一郎, 中野靖浩, 大塚文男

日本内分泌学会雑誌 98 ( 5 ) 1302 - 1302 2023年3月

若年男性の橋本病による粘液水腫の1例

山本紘一郎, 本多寛之, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 5 ) 1303 - 1303 2023年3月

ハンセン病に対する免疫抑制療法を背景に発症した播種性糞線虫症の1例

中本健太, 萩谷英大, 平佑貴, 庵谷紘美, 中野靖浩, 長谷川功, 大塚文男

感染症学雑誌 97 ( 2 ) 52 - 57 2023年3月

記述言語：日本語出版者・発行元：(一社)日本感染症学会

症例は30歳代ネパール人男性で、下痢と嘔気を主訴とした。ハンセン病(LL型)と新型コロナウイルス感染症の既往があり、らい反応に対して長期間のステロイド製剤内服による免疫抑制療法を行っていた。各種検査所見より、糞線虫の過剰感染状態による播種性糞線虫症と診断した。栄養状態は不良で、寄生虫の消化管内過剰増殖に伴う腸管浮腫を認め、イベルメクチンは吸収不良で血中濃度が不十分であった。多臓器不全を併発したため集学的治療を行ったが第36病日に死亡した。日本では糞線虫症は稀であるが、インバウンドの増加に伴い播種性糞線虫症のリスクが増加する可能性があり、ステロイドの長期内服などで免疫抑制状態の可能性がある場合は寄生虫スクリーニングを行う必要があると考えられた。

【臨床検査で患者を救え!-知っておいてほしい疾患】重度で長期の甲状腺機能低下症

越智可奈子, 中野靖浩, 原田洸, 長谷川功, 大塚文男

臨床検査 67 ( 3 ) 246 - 253 2023年3月

プラスミノーゲン欠乏症に腸管型ベーチェット病を合併し広範な皮膚粘膜病変を発症した一例

中土井崇人, 勝山恵理, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 大塚文男, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 795 - 795 2023年3月

ハンセン病に対する免疫抑制療法を背景に発症した播種性糞線虫症の1例

中本健太, 萩谷英大, 平佑貴, 庵谷紘美, 中野靖浩, 長谷川功, 大塚文男

感染症学雑誌 97 ( 2 ) 52 - 57 2023年3月

記述言語：日本語出版者・発行元：(一社)日本感染症学会

ビジュアルで見るプライマリ・ケア毒針毛による皮膚炎

大塚勇輝, 長岡寛和, 花山宜久, 大塚文男, 金森達也

日本プライマリ・ケア連合学会誌 46 ( 1 ) 33 - 34 2023年3月

若年男性の橋本病による粘液水腫の1例

山本紘一郎, 本多寛之, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 5 ) 1303 - 1303 2023年3月

Buruli ulcer caused by Mycobacterium ulcerans subsp. shinshuense: A case report. 査読国際誌

Takumi Fujimori, Hideharu Hagiya, Koji Iio, Osamu Yamasaki, Yuji Miyamoto, Yoshihiko Hoshino, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 29 ( 5 ) 523 - 526 2023年2月

記述言語：英語

Buruli ulcer is the third most common mycobacterial infection worldwide and is mainly diagnosed in tropical regions. Globally, this progressive disease is caused by Mycobacterium ulcerans; however, Mycobacterium ulcerans subsp. shinshuense, an Asian variant, has been exclusively identified in Japan. Because of insufficient clinical cases, the clinical features of M. ulcerans subsp. shinshuense-associated Buruli ulcer remain unclear. A 70-year-old Japanese woman presented with erythema on her left backhand. The skin lesion deteriorated without an apparent etiology of inflammation, and she was referred to our hospital 3 months after disease onset. A biopsy specimen was incubated in 2% Ogawa medium at 30 °C. After 66 days, we detected small yellow-pigmented colonies, suggesting scotochromogens. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI Biotyper; Bruker Daltonics, Billerica, MA, USA) indicated that the organism was Mycobacterium pseudoshottsii or Mycobacterium marinum. However, additional PCR testing for the insertion sequence 2404 (IS2404) was positive, suggesting that the pathogen was either M. ulcerans or M. ulcerans subsp. shinshuense. Further examination by 16S rRNA sequencing analysis, focusing on nucleotide positions 492, 1247, 1288, and 1449-1451, we finally identified the organism as M. ulcerans subsp. shinshuense. The patient was successfully treated with 12 weeks of clarithromycin and levofloxacin treatment. Mass spectrometry is the latest microbial diagnostic method; however, it cannot be used to identify M. ulcerans subsp. shinshuense. To accurately detect this enigmatic pathogen and uncover its epidemiology and clinical characteristics in Japan, more accumulation of clinical cases with accurate identification of the causative pathogen is essential.

DOI： 10.1016/j.jiac.2023.02.009

Trends in the Incidence of Japanese Spotted Fever in Japan: A Nationwide, Two-Decade Observational Study from 2001-2020. 査読国際誌

Yuki Otsuka, Hideharu Hagiya, Shinnosuke Fukushima, Ko Harada, Toshihiro Koyama, Fumio Otsuka

The American journal of tropical medicine and hygiene 2023年2月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

The worldwide spread of tick-borne diseases (TBDs) has become a public health concern. Therefore, this study aimed to clarify trends in the incidence of Japanese spotted fever (JSF), one of Japan's most prevalent TBDs. Weekly infectious disease reports were used to calculate the annual incidence rates (AIRs) of JSF. Data were stratified by age and sex, and joinpoint regression analysis was performed to estimate the annual percentage change (APC). AIR and APC were geographically compared among the 47 prefectures. A total of 3,453 JSF cases were observed from 2001 to 2020. The AIR per 100,000 population was 0.03 in 2001, which increased approximately 10-fold to 0.33 in 2020. The average APC (AAPC) during the study period was 12.3% (95% CI: 10.7-13.9). By age group, the incidence of JSF increased more rapidly among the older population: 11.5% (95% CI: 10.1-12.9) in those aged ≥ 65 years and 8.9% (95% CI: 6.4-11.5) in those aged < 50 years. Although the AIR over the past two decades was higher in climatically warm regions located in southwestern Japan and on the Pacific coast, increases in the AAPC were notable in colder regions located in eastern Japan. The incidence of JSF continues to increase in Japan, especially among older populations and in eastern prefectures, where the disease has not been previously diagnosed.

DOI： 10.4269/ajtmh.22-0487

コロナ禍にCaSR作動薬で長期管理し得た原発性副甲状腺機能亢進症の一例

Mediastinal Abscess Induced by Group B Streptococcus 査読

Kenta Nakamoto, Hideharu Hagiya, Ruiko Hayashi, Fumio Otsuka

Internal Medicine 62 ( 3 ) 491 - 492 2023年2月

大上莉央, 大塚勇輝, 中野靖浩, 高瀬了輔, 山下茉奈美, 山本紘一郎, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 4 ) 1079 - 1079 2023年2月

成人期にPHEX新規変異によるX染色体連鎖性低リン血症性骨軟化症と診断した1例

山本紘一郎, 本多寛之, 高瀬了輔, 中野靖浩, 徳増一樹, 長谷川功, 長谷川高誠, 大塚文男

日本内分泌学会雑誌 98 ( 4 ) 1080 - 1080 2023年2月

臨床検査室におけるナノポアシーケンシング技術を用いた新型コロナウイルス感染症の疫学的解析実用化に向けての取り組み

飯尾耕治, 後藤和義, 萩谷英大, 小川寛人, 三好諒, 大塚文男, 東影明人

医学検査 72 ( 2 ) 248 - 255 2023年2月

Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B (inducible MLSB) Resistance in Clindamycin-Susceptible Staphylococcus aureus at Okayama University Hospital. 査読

Lutfun Nahar, Hideharu Hagiya, Takahiro Nada, Koji Iio, Kazuyoshi Gotoh, Osamu Matsushita, Fumio Otsuka

Acta Medica Okayama 77 ( 1 ) 1 - 9 2023年2月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Inducible resistance to the macrolide, lincosamide, and streptogramin B (iMLSB) antibiotic family is a latent mechanism for antimicrobial resistance in Staphylococcus aureus. We here investigated the frequency and genotypic profiles of iMLSB resistance in clindamycin (CLDM)-susceptible S. aureus isolated in Okayama University Hospital from June 2020 to June 2021. We phenotypically screened the iMLSB resistance via D-zone test and performed PCR testing for the erythromycin ribosomal methylase (erm) genes: ermA and ermC. Among 432 CLDM-susceptible S. aureus isolates, 138 (31.9%) exhibited an iMLSB-resistance phenotype, with methicillinresistant S. aureus isolates (MRSA; 61 isolates: 58.6%) exhibiting higher positivity than methicillin-sensitive S. aureus isolates (MSSA; 77 isolates: 23.5%) (p<0.001). Male patients had a higher frequency of iMLSB resistance than females (OR [95%CI]: 1.8 [1.2-2.8]; p=0.007). Genotypically, ermA predominated in both MSSA (70.1%) and MRSA (86.9%) compared to ermC (14.3% in MSSA and 11.5% in MRSA). A single strain of MRSA possessed both ermA and ermC, while 12 (15.6%) MSSA isolates were negative for both ermA and ermC, suggesting the presence of other genetic mechanisms. Collectively, these results show that approximately 33% of CLDM-susceptible S. aureus isolates at our university hospital exhibited iMLSB resistance, predominantly caused by ermA in both MSSA and MRSA.

DOI： 10.18926/AMO/64355

不明熱の原因となるカンピロバクター菌血症の臨床的特徴に関する多施設後方研究

大塚勇輝, 萩谷英大, 高橋美砂, 福島伸乃介, 前田瑠璃, 砂田匠彦, 山田晴士, 岸田雅之, 藤田浩二, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増1 ) 214 - 214 2023年2月

COVID-19罹患後症状と血清亜鉛濃度の関連

松田祐依, 徳増一樹, 大塚勇輝, 砂田匠彦, 本多寛之, 櫻田泰江, 中野靖浩, 長谷川徹, 萩谷英大, 小比賀美香子, 植田圭吾, 片岡仁美, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増1 ) 168 - 168 2023年2月

COVID-19罹患後にME/CFSに移行する症例の臨床的特徴血清ferritinと内分泌系に注目した検討

山本幸近, 大塚勇輝, 徳増一樹, 萩谷英大, 砂田匠彦, 本多寛之, 中野靖浩, 櫻田泰江, 松田祐依, 長谷川徹, 長谷川功, 小比賀美香子, 植田圭吾, 片岡仁美, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増1 ) 173 - 173 2023年2月

大腿骨頸部骨折を契機に発見されたビタミンD欠乏の1例

高瀬了輔, 本多寛之, 中野靖浩, 山本紘一郎, 大國皓平, 越智可奈子, 長谷川功, 三好智子, 花山宜久, 小川弘子, 森泰宏, 大塚文男

日本病院総合診療医学会雑誌 19 ( 臨増1 ) 223 - 223 2023年2月

Trends in Long COVID Symptoms in Japanese Teenage Patients. 査読国際誌

Yasue Sakurada, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Hiroyuki Honda, Yasuhiro Nakano, Yui Matsuda, Toru Hasegawa, Kanako Ochi, Hideharu Hagiya, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Medicina (Kaunas, Lithuania) 59 ( 2 ) 2023年1月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.

DOI： 10.3390/medicina59020261

Tuberculous meningitis 査読

Shinnosuke Fukushima, Kazuki Ocho, Koji Fujita, Hideharu Hagiya, Fumio Otsuka

Clinical Case Reports 11 ( 1 ) 2023年1月

Differences in Stress Perception of Medical Students Depending on In-Person Communication and Online Communication during the COVID-19 Pandemic: A Japanese Cross-Sectional Survey. 査読国際誌

Kazuki Tokumasu, Yoshito Nishimura, Yoko Sakamoto, Mikako Obika, Hitomi Kataoka, Fumio Otsuka

International journal of environmental research and public health 20 ( 2 ) 2023年1月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Excessive psychological stress in medical students affects their mental health and causes problems such as burnout and depression. Furthermore, changes in the learning environment to online learning due to the COVID-19 pandemic have had a psychological effect on medical students. However, the relationships between medical students' perceived stress and different methods of communication, including in-person and online communication, remain unclear. The purpose of this study was to investigate the differences in stress perception of medical students depending on in-person communication and online communication during the COVID-19 pandemic. METHODS: This study was a cross-sectional study conducted from September to October in 2020. All of the students of Okayama University School of Medicine were asked to participate in a questionnaire survey. The explanatory variables were the frequency and length of communications with others (by in-person or online communication), empathy, and lifestyle. The main outcome measure was perceived stress. Subgroup analysis was conducted for students who preferred to be by themselves and students who preferred to study together and interact with other people. Univariate analysis and multivariate multiple regression analysis were conducted. Gender and grade, which have been shown to be associated with stress in previous studies, were used as covariates for multiple regression analysis. RESULTS: Valid responses to the questionnaire survey were received from 211 (29.4%) of the 717 students. There was no significant association between perceived stress and online communication, but the number of people with which students had in-person communication (1-2 people compared to 0 as a control, regression coefficient [B] = -4.4, 95% confidence interval [CI]; -7.8, -1.1, more than 10 people, B = -12, 95% CI: -18, -5.8) and the length of communication (more than 120 min, B = -4.5, 95% CI: -8.1, -0.92) were associated with a reduction in perceived stress. In subgroup analysis, the number of people with in-person communication and the length of communication had significant associations with stress reduction even in the group of students who had a preference for being by themselves. CONCLUSION: In-person communications rather than online communications were associated with a lower level of perceived stress. In subgroup analysis, this trend was statistically significant in the group of students who had a preference for being by themselves.

DOI： 10.3390/ijerph20021579

Clinical characteristics of Campylobacter bacteremia: a multicenter retrospective study. 査読国際誌

Yuki Otsuka, Hideharu Hagiya, Misa Takahashi, Shinnosuke Fukushima, Ruri Maeda, Naruhiko Sunada, Haruto Yamada, Masayuki Kishida, Koji Fujita, Fumio Otsuka

Scientific reports 13 ( 1 ) 647 - 647 2023年1月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Campylobacter species are the pathogens of the intestinal tract, which infrequently cause bacteremia. To reveal the clinical characteristics of Campylobacter bacteremia, we performed a retrospective, multicenter study. Patients diagnosed with Campylobacter bacteremia in three general hospitals in western Japan between 2011 and 2021 were included in the study. Clinical, microbiological, and prognostic data of the patients were obtained from medical records. We stratified the cases into the gastroenteritis (GE) and fever predominant (FP) types by focusing on the presence of gastrointestinal symptoms. Thirty-nine patients (24 men and 15 women) were included, with a median age of 57 years and bimodal distribution between those in their 20 s and the elderly. The proportion of GE and FP types were 21 (53.8%) and 18 (46.2%), respectively. Comparing these two groups, there was no significant difference in patient backgrounds in terms of sex, age, and underlying diseases. Campylobacter jejuni was exclusively identified in the GE type (19 cases, 90.5%), although other species such as Campylobacter fetus and Campylobacter coli were isolated in the FP type as well. Patients with the FP type underwent intravenous antibiotic therapy more frequently (47.6% vs. 88.9%), and their treatment (median: 5 days vs. 13 days) and hospitalization (median: 7 days vs. 21 days) periods were significantly longer. None of the patients died during the hospitalization. In summary, we found that nearly half of the patients with Campylobacter bacteremia presented with fever as a predominant manifestation without gastroenteritis symptoms.

DOI： 10.1038/s41598-022-27330-4

Late-Onset Neutropenia With Clozapine Associated With Lithium Carbonate–Related Hyperthyroidism 査読

Takayasu Arteritis Mimicking Phlegmon 査読

Yuki Taira, Yasuhiro Nakano, Yoshihisa Hanayama, Fumio Otsuka

Internal Medicine 62 ( 1 ) 149 - 149 2023年1月

Oxytocin enhances progesterone production with upregulation of BMP-15 activity by granulosa cells 査読

Koichiro Yamamoto, Yasuhiro Nakano, Nahoko Iwata, Yoshiaki Soejima, Atsuhito Suyama, Toru Hasegawa, Fumio Otsuka

Biochemical and Biophysical Research Communications 646 103 - 109 2023年1月

Yuto Yamada, Masaki Fujiwara, Shuhei Tsujino, Satoru Edahiro, Shinji Sakamoto, Koichiro Yamamoto, Fumio Otsuka, Norihito Yamada, Manabu Takaki

Journal of Clinical Psychopharmacology 43 ( 1 ) 76 - 77 2023年1月

Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model 査読

Naomi Matsumoto, Hideharu Hagiya, Masanori Nakayama, Masanori Furukawa, Toshiharu Mitsuhashi, Soshi Takao, Fumio Otsuka, Takashi Yorifuji

Journal of Infection and Chemotherapy 29 ( 1 ) 39 - 42 2023年1月

Antimicrobials in the Hospital are Unevenly Discontinued on Weekdays 査読

Hideharu Hagiya, Mika Uno, Tsukasa Higashionna, Hiroyuki Honda, Fumio Otsuka

Internal Medicine 2023年

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Society of Internal Medicine

Objective Amid the global spread of antimicrobial resistance, antimicrobial stewardship should be further promoted in the clinical setting. Our previous study suggested an intra-week disproportion of discontinuation of broad-spectrum antibiotics. We therefore explored the generalization of this prescription trend by investigating the use of all intravenous antibiotics. Methods A retrospective, observational study. Patients Between January 1, 2018, and December 31, 2020, we collected data on the initiation and discontinuation of intravenous antimicrobials on each day of the week and on days after holidays at Okayama University Hospital, Japan. We compared the monthly antimicrobial prescription initiation and discontinuation using the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction as a post-hoc procedure. Results Data from 15,293 hospitalized cases were analyzed. The initiation of antimicrobials differed slightly among days of the week, although this trend was clinically insignificant. Compared with the initiations, antimicrobial discontinuations were disproportionately biased among the weekdays, tending to occur on Mondays (p <0.001) about twice as often as on other days. Similarly, antimicrobials were unevenly discontinued on the day after holidays compared to other days (p <0.001), with an approximately 2-fold difference. The use of antimicrobials in the hospital was thus unequally terminated on weekdays. Conclusion To further promote antimicrobial stewardship, clinicians should be aware of the influence of behavioral, environmental, and social factors on antimicrobial prescription, which is seemingly beyond medical indications.

DOI： 10.2169/internalmedicine.0707-22

Biofilm-associated candidal thrombophlebitis 査読

Shinnosuke Fukushima, Koichiro Yamamoto, Yasuhiro Nakano, Hideharu Hagiya, Fumio Otsuka

IDCases 31 e01733 - e01733 2023年

Contributions of Japanese Hospitalists During the COVID-19 Pandemic and the Need for Infectious Disease Crisis Management Education for Hospitalists: An Online Cross-Sectional Study. 査読国際誌

Masaki Tago, Risa Hirata, Naoko E Katsuki, Yuki Otsuka, Taro Shimizu, Yosuke Sasaki, Kiyoshi Shikino, Takashi Watari, Hiromizu Takahashi, Kazunobu Une, Toshio Naito, Fumio Otsuka, Rachel Thompson, Susumu Tazuma

Risk management and healthcare policy 16 1645 - 1651 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Hospitalists in Japan have been at the forefront of the COVID-19 pandemic. However, contributions of Japanese hospitalists during the COVID-19 pandemic and hospitalists' awareness of crisis management education remain unclear. MATERIAL AND METHODS: We conducted a questionnaire survey to investigate the role of Japanese hospitalists during the COVID-19 pandemic. The questionnaire was conducted using email and Google Forms targeting the chairpersons of facilities certified by the Japanese Society of Hospital General Medicine (JSHGM). Members of the academic committee of the JSHGM and several hospitals conducted a narrative review and determined the questions for the survey in a discussion. RESULTS: We conducted descriptive statistics based on the responses of 97 hospitals that agreed to participate in this survey. In total, 91.8% of general medicine departments in the included hospitals were involved in the medical care of COVID-19 patients. Furthermore, in 73.2% of hospitals, hospitalists were involved in infection control for COVID-19 inside or outside the hospital. Our survey revealed that Japanese hospitalists were responsible for COVID-19 treatment in over 60% of hospitals and contributed to hospital management, infection control, and vaccination. In total, 79.4% of hospitals answered that "training of personnel who can provide practical care for emerging infectious diseases is necessary", 78.4% indicated that "the establishment of an infection control system in advance to prepare emerging infectious diseases in the hospital is necessary", and 74.2% stated that "the establishment of an educational system for responding to emerging infectious diseases is necessary.". CONCLUSION: In conclusion, during the pandemic, in addition to inpatient care, Japanese hospitalists provided outpatient care for COVID-19, which is the role of primary care physicians in other countries. Furthermore, Japanese hospitalists who experienced the COVID-19 pandemic expressed the need for personnel development and education to prepare for future emerging infectious disease pandemics.

DOI： 10.2147/RMHP.S422412

Cryptococcal Meningitis Developing in a Patient with Neurosarcoidosis 査読

Ossification of the Posterior Longitudinal Ligament Caused by X-linked Hypophosphatemia 査読

Koichiro Yamamoto, Kosei Hasegawa, Takao Yasuhara, Fumio Otsuka

2023年

Shinnosuke Fukushima, Hideharu Hagiya, Yukichika Yamamoto, Kohei Oguni, Kou Hasegawa, Fumio Otsuka

Internal Medicine 2023年

Characteristics of Sleep Disturbance in Patients with Long COVID: A Retrospective Observational Study in Japan. 査読国際誌

Naruhiko Sunada, Yasuhiro Nakano, Yuki Otsuka, Kazuki Tokumasu, Hiroyuki Honda, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Daisuke Omura, Kanako Ochi, Hideharu Hagiya, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Journal of clinical medicine 11 ( 24 ) 2022年12月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: The objective of this study was to determine the clinical and endocrinological features of sleep disturbance in patients with long COVID. METHODS: This study was a single-center retrospective observational study for patients who visited the COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital in Japan during the period from 15 February 2021 to 29 July 2022. The long COVID patients were divided into two groups based on the presence or absence of sleep disturbance, and the clinical and laboratory characteristics of the patients were analyzed. RESULTS: Out of 363 patients with long COVID, after excluding 6 patients, 60 patients (16.5%) (55% males, median age of 38 years) complaining of sleep disturbance were compared with 303 patients (83.5%) (43% males, median age of 40 years) without sleep-related symptoms. Although there were no significant differences in clinical backgrounds and severities of COVID-19 between the two groups by the multivariate analysis, the percentage of long COVID patients with sleep disturbance was significantly increased among patients infected in the Omicron-dominant phase. In addition, the prevalence rate of sleep disturbance in patients when infected in the Omicron phase (24.8%) was two-times higher than that in patients infected in the Delta phase (12.8%). Of note, the percentages of patients with sleep disturbance who also complained of general fatigue, headache, concentration loss, anxiety, low-grade fever, and brain fog symptoms were higher than the percentages of patients without sleep disturbance who had the same complaints. Among the types of sleep disturbance, the percentage of patients who complained of loss of sleep induction (75%) was much higher than the percentage of patients with early-awakening sleep disturbance (6.7%), and many of the patients with mid-awakening types of insomnia had brain fog symptoms. Endocrine examinations revealed that long COVID patients with sleep disturbance had significantly higher levels of plasma adrenocorticotropin and lower levels of serum growth hormone, suggesting the presence of hypothalamic-pituitary stress. CONCLUSION: The prevalence of sleep disturbance has been increasing in long COVID patients infected in the Omicron phase with a certain clinical and endocrine trend.

DOI： 10.3390/jcm11247332

Key signs indicating mesenteric panniculitis 査読

Koichiro Yamamoto, Hiroyuki Honda, Hiroko Ogawa, Fumio Otsuka

Clinical Case Reports 10 ( 12 ) 2022年12月

Detection of Enterobacter cloacae complex strain with a blaNDM-1-harboring plasmid from an elderly resident at a long-term care facility in Okayama, Japan 査読国際誌

Kazuyoshi Gotoh, Hideharu Hagiya, Koji Iio, Haruto Yamada, Osamu Matsushita, Fumio Otsuka

Journal of Infection and Chemotherapy 28 ( 12 ) 1697 - 1699 2022年12月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

Amidst the global spread of antimicrobial resistance, New Delhi metallo-β-lactamase (NDM)-type carbapenemase-producing Enterobacterales (CPE) remain uncommon in Japan, and the detection of such highly drug-resistant organisms is limited to inbound cases. There is little evidence regarding the prevalence of NDM β-lactamase gene (blaNDM)-harboring CPE in the domestic community, especially in the provincial cities of Japan. Herein, we report the isolation of a blaNDM-1-harboring plasmid in Enterobacter cloacae complex strain isolated from an elderly woman without a history of traveling abroad who had resided in a long-term care facility in Okayama, Japan. The multidrug-resistant blaNDM-harboring CPE isolate was detected in a stool sample of the patient during routine screening at admission. We performed whole-genome sequencing analysis of the isolate using MiSeq (Illumina) and MinION (Oxford Nanopore Technologies) platforms. The isolate was identified as sequence type 171, which has predominantly been reported in the United States and China. The blaNDM-1 gene was encoded on the 46,161 bp IncX3 plasmid, with sequence similarity to plasmids of similar size isolated from individuals in China. Collectively, the genomic data suggest that an imported CPE isolate may have spread among healthy individuals in the regional area of Japan.

DOI： 10.1016/j.jiac.2022.08.019

医療系学部教育でのIPE(Inter-professional Education:多職種連携教育)の実践を通した患者中心の医療の経験

Rhinogenic optic neuropathy with hemianopia caused by ethmoidal sinus mucocele. 査読国際誌

Kosuke Oka, Wataru Ando, Hideharu Hagiya, Takaya Higaki, Fumio Otsuka

Clinical case reports 10 ( 12 ) e6696 2022年12月

三好智子, 岩室雅也, 花山宜久, 小川弘子, 小比賀美香子, 名倉弘哲, 大塚文男

医学教育 53 ( 6 ) 531 - 536 2022年12月

記述言語：日本語出版者・発行元：(一社)日本医学教育学会

本研究では,医療系学生が小グループのIPEの実践を通して,患者中心のチーム医療を実践したと考えることができたかを検証した.医学科,薬学科,保健学科の臨床実習中の学部学生に対し,小グループで症例基盤型の臨床推論と治療・看護計画立案を行い,IPEに対するアンケートを行った.医学科生は臨床推論と治療計画立案が,薬学科生は治療の副作用対策を提案することが,看護学生は医療チームに必要な情報提供をすることが,医療チームとともに患者中心の医療が実践できたと感じていた.学部毎にチーム医療を実践したと考える項目が異なり,多学部合同IPEにはそれぞれの要素を組み込むことが重要である.(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00050&link_issn=&doc_id=20230117110006&doc_link_id=%2Fed9jmded%2F2022%2F005306%2F007%2F0531-0536%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fed9jmded%2F2022%2F005306%2F007%2F0531-0536%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing 査読

Hideharu Hagiya, Yasuhiro Nakano, Masanori Furukawa, Naruhiko Sunada, Toru Hasegawa, Yasue Sakurada, Kou Hasegawa, Koichiro Yamamoto, Hiroko Ogawa, Takafumi Obara, Kouhei Ageta, Naomi Matsumoto, Rumi Matsuo, Tomoka Kadowaki, Akihito Higashikage, Takao Hikita, Takashi Yorifuji, Shinichi Toyooka, Yoshinobu Maeda, Yoshinori Yokokura, Fumio Otsuka, Masanori Nakayama

Scientific Reports 12 ( 1 ) 2022年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

DOI： 10.1038/s41598-022-24464-3

Letter to the Editor From Yamamoto et al: “Whole Body, Whole Life, Whole Family: Patients’ Perspectives on X-Linked Hypophosphatemia” 査読

その他リンク： https://www.nature.com/articles/s41598-022-24464-3

Koichiro Yamamoto, Daisuke Omura, Keiji Soga, Mikako Obika, Fumio Otsuka

Journal of the Endocrine Society 7 ( 1 ) 2022年11月

Right-sided infective endocarditis with odontogenic infections 査読国際誌

S Fukushima, K Fujita, H Hagiya, F Otsuka

QJM: An International Journal of Medicine 115 ( 11 ) 753 - 753 2022年11月

A Wolff–Parkinson–White syndrome revealed by the event of heat stroke 査読国際誌

S Tanaka, H Hagiya, F Otsuka

QJM: An International Journal of Medicine 115 ( 11 ) 760 - 761 2022年11月

High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital 査読国際誌

Hideharu Hagiya, Yuji Onishi, Natsumi Shinohara, Mayumi Tokuyasu, Aki Imanishi, Shinnosuke Fukushima, Lutfun Nahar, Koji Iio, Fumio Otsuka

Journal of Infection and Chemotherapy 28 ( 11 ) 1578 - 1581 2022年11月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

INTRODUCTION: Long-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic. METHODS: We performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers. RESULTS: Stool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The blaCTX-M-9 group was the most common (38.5%), followed by the blaTEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different. CONCLUSION: Our active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather.

DOI： 10.1016/j.jiac.2022.07.014

Trends in the incidence of syphilis in the middle‐aged and older adults in Japan: A nationwide observational study, 2009–2019 査読

Misa Takahashi, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Geriatrics and Gerontology International 2022年11月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

AIM: Sexually transmitted infections remain a neglected area of research in geriatrics. However, in the global aging societies, sexual health among the middle-aged and older adults is an emerging public concern. High-income countries are facing a resurgence of syphilis cases among young generations, but little is known about its prevalence in older populations. We aimed to investigate the national trend of syphilis cases in Japan. METHODS: This nationwide observational study used the publicly-available database (2009-2019) to calculate crude and age-adjusted incidence rates of syphilis per 100 000 population by age, sex and clinical stage. We collected data from patients aged ≥50 years and performed joinpoint regression analysis to estimate long-term trends and average annual percentage changes (AAPCs). RESULTS: The total number of patients with syphilis increased about 8-fold from 165 in 2009 to 1280 in 2019. AAPCs of crude incidence rates significantly increased in every age category; 33.2% in 50-59 years, 23.8% in 60-69 years and 20.9% in ≥70 years. Age-adjusted incidence rates have surged at AAPCs of 28.7% in men and 23.1% in women, reaching 4.09 in men and 0.71 in women in 2019. By clinical stage, marked increases were observed in primary (AAPCs, 42.3% in men and 41.6% in women) and secondary syphilis (AAPCs, 24.9% in men and 24.2% in women). CONCLUSIONS: An up-toward trend of syphilis among people aged ≥50 years was observed. The importance of sexual health among older people should be highlighted in this aging Japanese society. Geriatr Gerontol Int 2022; ••: ••-••.

DOI： 10.1111/ggi.14500

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ggi.14500

Isolated unilateral absence of adult pulmonary artery 査読

Koichiro Yamamoto, Yasuhiro Nakano, Fumio Otsuka

Clinical Case Reports 10 ( 11 ) 2022年11月

Increased CCR4+ and Decreased Central Memory CD4+ T Lymphocytes in the Background Gastric Mucosa of Patients Developing Gastric Cancer After Helicobacter pylori Eradication: An Exploratory Study. 査読国際誌

Masaya Iwamuro, Takahide Takahashi, Araki Hirabata, Takehiro Tanaka, Fumio Otsuka, Horoyuki Okada

Cureus 14 ( 11 ) e31713 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

The composition of lymphocytes in the gastric mucosa following the eradication of Helicobacter pylori (H. pylori) in patients with and without gastric cancer has not been compared. This study performed a single spot analysis of gastric mucosal lymphocytes after H. pylori eradication in patients with (n = 13) and without (n = 20) gastric cancer. Our comprehensive analysis of lymphocyte composition in the gastric mucosa revealed that: i) the proportion of CD8+/CD3+ cells was relatively higher in the peri-tumor mucosa than in the background mucosa; ii) the proportion of CCR4+/CD3+ cells was higher, and the ratio of CD62L+/CD3+CD4+ cells was relatively lower in the gastric mucosa of cancer patients than in non-cancer patients; and iii) the proportion of CD45RA-CD62L+/CD3+CD4+ cells, namely, the central memory CD4+ T-cell fraction, was lower in the gastric mucosa of cancer patients than in non-cancer patients. Although the exact mechanism of the altered proportions of CCR4+/CD3+ and central memory CD4+ cells in the gastric mucosa of patients with cancer is unknown, focusing on lymphocytes in the gastric mucosa might help improve our understanding of gastric cancer development after H. pylori eradication.

DOI： 10.7759/cureus.31713

Postprandial reactive hypoglycemia detected with premature ventricular contraction 査読

男性2型糖尿病患者における血中アンドロゲン値とその意義

浜原潤, 本多寛之, 山本絋一郎, 中野靖浩, 徳増一樹, 花山宜久, 萩谷英大, 小比賀美香子, 植田圭吾, 岸田雅之, 大塚文男

糖尿病 65 ( 11 ) 633 - 633 2022年11月

H Honda, S Tanaka, H Hagiya, F Otsuka

QJM: An International Journal of Medicine 115 ( 10 ) 675 - 676 2022年10月

投稿 GM Report 専攻医から見た新専門医制度における総合診療専攻医の育成

大塚勇輝, 小比賀美香子, 大塚文男

総合診療 32 ( 10 ) 1274 - 1275 2022年10月

Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan 査読国際誌

Yasuhiro Nakano, Yuki Otsuka, Hiroyuki Honda, Naruhiko Sunada, Kazuki Tokumasu, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Kanako Ochi, Hideharu Hagiya, Hitomi Kataoka, Keigo Ueda, Fumio Otsuka

Medicina 58 ( 10 ) 1393 - 1393 2022年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized.

DOI： 10.3390/medicina58101393

Clinical and microbiological characteristics of polymicrobial bacteremia: a retrospective, multicenter study. 査読国際誌

Shinnosuke Fukushima, Hideharu Hagiya, Koji Fujita, Shinya Kamiyama, Haruto Yamada, Masayuki Kishida, Fumio Otsuka

Infection 50 ( 5 ) 1233 - 1242 2022年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To clarify the clinical and microbial characteristics of polymicrobial bacteremia (PMB) to contribute to improvements in clinical diagnosis and effective early treatment. METHODS: This retrospective multicenter study used data from three acute-care hospitals in Okayama Prefecture, Japan, collected between January 2014 and March 2019. We reviewed the demographics, comorbidities, organisms isolated, infectious focus, and 30-day mortality of patients with PMB. RESULTS: Of the 7233 positive blood cultures, 808 (11.2%) were positive for more than one organism. Of the patients with bacteremia, 507 (7.0%) had PMB, of whom 65.3% were male. Infectious foci were identified in 78.3% of the cases, of which intra-abdominal infections accounted for 47.1%. A combination of Gram-positive cocci (GPC) (chain form) and Gram-negative rods (GNR) accounted for 32.9% of the cases, and GPC/GNR and GNR/GNR patterns were significantly associated with intra-abdominal infections. The 30-day mortality rate of patients with PMB was 18.1%, with a median of 7.5 days from diagnosis to death. The mortality in patients with an infectious focus identified was significantly lower than that in patients with an unknown focus (16.3% vs. 24.5%; p = 0.031). CONCLUSIONS: Intra-abdominal infections were the most common source of PMB, and were strongly associated with a Gram-staining combination pattern of GPC (chain form)/GNR. PMB cases with an unknown focus had a poorer prognosis, highlighting the importance of early diagnosis and appropriate treatment.

DOI： 10.1007/s15010-022-01799-7

新規PHEXバリアントを伴うXLHにブロスマブが奏効した1例

山本紘一郎, 本多寛之, 中野靖浩, 徳増一樹, 長谷川功, 長谷川高誠, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 591 - 591 2022年10月

COVID-19罹患後症状における内分泌機能に関する検討

砂田匠彦, 本多寛之, 中野靖浩, 山本絋一郎, 徳増一樹, 櫻田泰江, 松田祐依, 長谷川徹, 大塚勇輝, 小比賀美香子, 花山宜久, 萩谷英大, 植田圭吾, 片岡仁美, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 628 - 628 2022年10月

Kikuchi–Fujimoto disease manifesting bilateral lymphadenopathy 査読国際誌

Akihiro Kawatsuki, Kosuke Oka, Hideharu Hagiya, Fumio Otsuka

Clinical Case Reports 10 ( 10 ) e6494 2022年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Physicians should keep in mind that Kikuchi-Fujimoto disease can show bilateral lymphadenopathy like the present case.

DOI： 10.1002/ccr3.6494

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.6494

Candida dubliniensis fungemia in a patient with severe COVID-19: A case report 査読国際誌

Ayaka Kakehi, Hideharu Hagiya, Koji Iio, Yasuhiro Nakano, Hiromi Ihoriya, Yuki Taira, Kenta Nakamoto, Kou Hasegawa, Akihito Higashikage, Fumio Otsuka

Journal of Infection and Chemotherapy 28 ( 10 ) 1433 - 1435 2022年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

Candida dubliniensis phenotypically mimics Candida albicans in its microbiological features; thus, its clinical characteristics have yet to be fully elucidated. Here we report the case of a 68-year-old Japanese man who developed C. dubliniensis fungemia during treatment for severe coronavirus disease 2019 (COVID-19). The patient was intubated and received a combination of immunosuppressants, including high-dose methylprednisolone and two doses of tocilizumab, as well as remdesivir, intravenous heparin, and ceftriaxone. A blood culture on admission day 11 revealed Candida species, which was confirmed as C. dubliniensis by mass spectrometry. An additional sequencing analysis of the 26S rDNA and ITS regions confirmed that the organism was 100% identical to the reference strain of C. dubliniensis (ATCC MYA-646). Considering the simultaneous isolation of C. dubliniensis from a sputum sample, the lower respiratory tract could be an entry point for candidemia. Although treatment with micafungin successfully eradicated the C. dubliniensis fungemia, the patient died of COVID-19 progression. In this case, aggressive immunosuppressive therapy could have caused the C. dubliniensis fungemia. Due to insufficient clinical reports on C. dubliniensis infection based on definitive diagnosis, the whole picture of the cryptic organism is still unknown. Further accumulation of clinical and microbiological data of the pathogen is needed to elucidate their clinical significance.

DOI： 10.1016/j.jiac.2022.07.007

Prevalence of medical factors related to aging among older car drivers: a multicenter, cross-sectional, descriptive study 査読国際誌

Hideharu Hagiya, Ryosuke Takase, Hiroyuki Honda, Yasuhiro Nakano, Yuki Otsuka, Hitomi Kataoka, Mika Uno, Keigo Ueda, Misa Takahashi, Hiroko Ogawa, Yoshihisa Hanayama, Fumio Otsuka

BMC Geriatrics 22 ( 1 ) 792 - 792 2022年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: An increasing number of older adults in Japan are at an increased risk of road traffic crashes. This study aimed to investigate the prevalence of potential underlying medical factors that increase the risk of road traffic crashes among older people. METHODS: This cross-sectional observational study was conducted in 11 medical institutions in Japan using self-administered questionnaires and physical examination from January to May 2021. The background and social data, data on the use of nursing care insurance, and clinical data suggestive of polypharmacy, sarcopenia, cognitive impairment, and frailty/oral frailty were obtained. The prevalence of these factors was compared between everyday and occasional drivers. RESULTS: Data of 127 patients were collected; their median (interquartile range) age was 73 (70-78) years. Of the total participants, 82 were men (64.6%) and 45 were women (35.4%). There were 77 everyday drivers and 50 occasional drivers. Of these, 121 (95.3%) had not applied for nursing care insurance, but the numbers of those who required help 1 and 2 were 1 (0.8%) and 3 (2.4%), respectively. Prevalence of medical factors was as follows: polypharmacy, 27.6%; sarcopenia, 8.7%; dementia, 16.4%; frailty, 15.0%; and oral frailty, 54.3%; it was not significantly different between every day and occasional drivers. Intention to return the car license was significantly higher among the occasional drivers (2.6% vs. 14.0%; odds ratio: 6.7, 95% confidence interval: 1.2-70.6, p = 0.024). CONCLUSION: We uncovered the prevalence of medical factors that can be associated with road traffic crashes among Japanese older people aged ≥ 65 years in our community.

DOI： 10.1186/s12877-022-03490-w

専攻医から見た新専門医制度における総合診療専攻医の育成

RAS/BRAF解析においてPCR-rSSO法とNGS法の併用による補完性が示された大腸癌の二例

山本英喜, 重安邦俊, 柳井広之, 井上博文, 松岡博美, 青江伯規, 東影明人, 藤井敬子, 大塚文男, 草野展周, 平沢晃

日本臨床検査医学会誌 70 ( 補冊 ) 258 - 258 2022年10月

異なる経過をたどった腎動脈狭窄を伴う高安動脈炎の2症例

武本梨佳, 内田治仁, 戸田洋伸, 岡本修吾, 竹内英実, 梅林亮子, 大塚文男, 伊藤浩, 和田淳

脈管学 62 ( Suppl. ) S195 - S195 2022年10月

大塚勇輝, 小比賀美香子, 大塚文男

総合診療 32 ( 10 ) 1274 - 1275 2022年10月

Weekly GH投与の有用性を認めた脂肪肝・糖尿病合併AGHDの3例

中野靖浩, 山本紘一郎, 高瀬了輔, 大國皓平, 長谷川功, 越智可奈子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 622 - 622 2022年10月

術前検査にて機能的SSTR発現が示唆されたインスリノーマの1例

大國皓平, 山本幸近, 福島伸乃介, 長谷川功, 井下尚子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 614 - 614 2022年10月

コロナ禍の若年男性に発症した著明な粘液水腫の1例

山本紘一郎, 本多寛之, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 578 - 578 2022年10月

中枢性尿崩症と眼瞼黄色腫から診断したErdheim-Chester病の3例

山本紘一郎, 高瀬了輔, 大國皓平, 中野靖浩, 岡浩介, 本多寛之, 長谷川功, 花山宜久, 小比賀美香子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 569 - 569 2022年10月

経過中にインスリノーマを認めた高齢2型糖尿病の1例

長岡寛和, 本多寛之, 斎藤光希, 田中秀一, 山本紘一郎, 石田智治, 長谷川功, 萩谷英大, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 620 - 620 2022年10月

心室期外収縮を契機に判明した反応性低血糖の1例

本多寛之, 田中秀一, 中野靖弘, 長谷川功, 萩谷英大, 小比賀美香子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 619 - 619 2022年10月

RAS/BRAF解析においてPCR-rSSO法とNGS法の併用による補完性が示された大腸癌の二例

山本英喜, 重安邦俊, 柳井広之, 井上博文, 松岡博美, 青江伯規, 東影明人, 藤井敬子, 大塚文男, 草野展周, 平沢晃

日本臨床検査医学会誌 70 ( 補冊 ) 258 - 258 2022年10月

経過中にインスリノーマを認めた高齢2型糖尿病の1例

長岡寛和, 本多寛之, 斎藤光希, 田中秀一, 山本紘一郎, 石田智治, 長谷川功, 萩谷英大, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 620 - 620 2022年10月

Weekly GH投与の有用性を認めた脂肪肝・糖尿病合併AGHDの3例

中野靖浩, 山本紘一郎, 高瀬了輔, 大國皓平, 長谷川功, 越智可奈子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 622 - 622 2022年10月

術前検査にて機能的SSTR発現が示唆されたインスリノーマの1例

大國皓平, 山本幸近, 福島伸乃介, 長谷川功, 井下尚子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 614 - 614 2022年10月

心室期外収縮を契機に判明した反応性低血糖の1例

本多寛之, 田中秀一, 中野靖弘, 長谷川功, 萩谷英大, 小比賀美香子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 619 - 619 2022年10月

コロナ禍の若年男性に発症した著明な粘液水腫の1例

山本紘一郎, 本多寛之, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 578 - 578 2022年10月

新規PHEXバリアントを伴うXLHにブロスマブが奏効した1例

山本紘一郎, 本多寛之, 中野靖浩, 徳増一樹, 長谷川功, 長谷川高誠, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 591 - 591 2022年10月

中枢性尿崩症と眼瞼黄色腫から診断したErdheim-Chester病の3例

山本紘一郎, 高瀬了輔, 大國皓平, 中野靖浩, 岡浩介, 本多寛之, 長谷川功, 花山宜久, 小比賀美香子, 大塚文男

日本内分泌学会雑誌 98 ( 2 ) 569 - 569 2022年10月

異なる経過をたどった腎動脈狭窄を伴う高安動脈炎の2症例

武本梨佳, 内田治仁, 戸田洋伸, 岡本修吾, 竹内英実, 梅林亮子, 大塚文男, 伊藤浩, 和田淳

脈管学 62 ( Suppl. ) S195 - S195 2022年10月

岡山大学病院中央採血室の待ち状況のYouTubeライブ配信について

東影明人, 青江伯規, 川下隆二, 藤井敬子, 山本英喜, 大塚文男

日本臨床検査医学会誌 70 ( 補冊 ) 166 - 166 2022年10月

Collaboration between generalist and ENT physicians in COVID-19 Omicron variant-induced laryngitis 査読国際誌

Yuki Otsuka, Kou Hasegawa, Yukichika Yamamoto, Asuka Sato, Ryotaro Omichi, Fumio Otsuka

Auris Nasus Larynx 50 ( 4 ) 652 - 653 2022年10月

Effects of Yoga and Mindfulness Programs on Self-Compassion in Medical Professionals during the COVID-19 Pandemic: An Intervention Study 査読国際誌

Tomoko Miyoshi, Hiromi Ida, Yoshito Nishimura, Soichiro Ako, Fumio Otsuka

International Journal of Environmental Research and Public Health 19 ( 19 ) 12523 - 12523 2022年9月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Stress among healthcare workers (HCWs) increased during the coronavirus disease 2019 pandemic. We aimed to determine whether a yoga and mindfulness program could alleviate burnout and other psychological and physical distress in HCWs, and how this might affect their empathy for patients. A weekly one-hour yoga and mindfulness program was conducted for three months in 2021. Participants were 18 consenting HCWs and, the final analysis included 13 participants. They responded to online questionnaires before and after the program. We measured salivary cortisol levels before and after the program on the first and last days. Self-measured pulse rates (PRs) were taken before and after each session, which decreased significantly in both cases (before, after the first program: 72, 65 bpm, p < 0.05; before, after the last program: 75, 66, p < 0.05), but salivary cortisol levels did not change. No significant changes were observed in Patient Health Questionnaire-9, Maslach Burnout Inventory, Sense of Coherence, Connor-Davidson Resilience Scale, Self-compassion Scale, or Jefferson Scale of Empathy. However, common humanity, a subscale of self-compassion, increased significantly (before the first program: 5.6, after the last program: 6.5, p < 0.05), and over-identification decreased significantly (7.9, 6.7, p < 0.01). Yoga and mindfulness programs may help improve the sense of common humanity and reduce over-identification in HCWs.

DOI： 10.3390/ijerph191912523

Secondary autoimmune hypothalamitis with severe memory impairment 7 years after the onset of diabetes insipidus due to lymphocytic hypophysitis: a case report 査読

Takahiro Asada, Shintaro Takenoshita, Mayuko Senda, Koichiro Yamamoto, Ryo Sasaki, Fumio Otsuka, Seishi Terada, Norihito Yamada

BMC Neurology 22 ( 1 ) 2022年9月

掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Background

Autoimmune hypothalamitis is a very rare neuroendocrine disorder that causes central diabetes insipidus, headache, visual impairment, and sometimes cognitive impairment. Autoimmune hypothalamitis may occur in association with autoimmune hypophysitis, including lymphocytic hypophysitis, or in isolation. It is not known whether autoimmune hypothalamitis and autoimmune hypophysitis are consecutive diseases.

Case presentation

A 52-year-old woman developed autoimmune hypothalamitis 7 years after developing central diabetes insipidus due to lymphocytic hypophysitis, resulting in severe memory impairment. High-dose intravenous methylprednisolone therapy improved her cognitive function and decreased the size of the lesion.

Conclusion

This case presented a unique clinical course, with a long period of time between the onset of autoimmune hypopituitaritis and the development of autoimmune hypothalamitis.

DOI： 10.1186/s12883-022-02891-z

その他リンク： https://link.springer.com/article/10.1186/s12883-022-02891-z/fulltext.html

Splenomegaly in silent endocarditis 査読

T Ishida, H Hagiya, Y Yamamoto, K Oguni, F Otsuka

QJM: An International Journal of Medicine 115 ( 9 ) 615 - 616 2022年9月

Impact of the cervical cancer awareness months on public interest in Japan: A Google Trends analysis, 2012–2021 査読国際誌

Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Scientific Reports 12 ( 1 ) 15391 - 15391 2022年9月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

The immunization and screening rates for human papillomavirus in Japan are lower than those in other countries. We aimed to evaluate the impact of cervical cancer awareness months on public attention using Google Trends analysis. Between 2012 and 2021, we analyzed the trends in relative search volumes (RSVs) for “Shikyuu-keigan” (cervical cancer in English) in Japan, during the cervical cancer awareness month (CCAM) in January and cervical cancer prevention awareness enhancement month (CCPAEM) in November. We performed a joinpoint regression analysis to identify a statistically significant trend change point. Additionally, we compared the mean RSVs of each awareness month with the rest of the year. Significant trend change points were observed, but none were found in CCAM and CCPAEM periods. Comparison of mean RSVs among CCAM, CCPAEM, and the rest of the months did not suggest any significant increases in RSVs during these awareness periods. In conclusion, CAM and CCPAEM did not raise public interest in cervical cancer in Japan. Although the results are based on internet users, the findings might suggest a need to develop a more effective and attractive approach to achieve the 90-70-90 targets of cervical cancer prevention by 2030.

DOI： 10.1038/s41598-022-19798-x

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease 査読

その他リンク： https://www.nature.com/articles/s41598-022-19798-x

Asami Nishikori, Midori Nishimura, Yoshito Nishimura, Fumio Otsuka, Kanna Maehama, Kumiko Ohsawa, Shuji Momose, Naoya Nakamura, Yasuharu Sato

International Journal of Molecular Sciences 23 ( 18 ) 10301 - 10301 2022年9月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p < 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p < 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD.

DOI： 10.3390/ijms231810301

感染症-脳神経外科医のためのエッセンス III 脳神経外科と感染症-特殊な病態とトピックス Long COVIDにおける中枢神経・精神関連合併症査読

萩谷英大, 大塚文男

Neurological Surgery 50 ( 5 ) 1071 - 1077 2022年9月

Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model 査読

Naomi Matsumoto, Hideharu Hagiya, Masanori Nakayama, Masanori Furukawa, Toshiharu Mitsuhashi, Soshi Takao, Fumio Otsuka, Takashi Yorifuji

Journal of Infection and Chemotherapy 2022年9月

Gap between self-evaluation and actual hand hygiene compliance among health-care workers 査読国際誌

Hideharu Hagiya, Ryosuke Takase, Yosuke Sazumi, Yoshito Nishimura, Hiroyuki Honda, Fumio Otsuka

Journal of Infection Prevention 23 ( 5 ) 239 - 242 2022年9月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SAGE Publications

Hand hygiene (HH) compliance among health-care workers has not satisfactorily improved despite multiple educative approaches. Between October 2019 and February 2020, we performed a self-evaluation test and a direct observation for the compliance of the 5 Moments for Hand Hygiene program advocated by the World Health Organization at two Japanese hospitals. Average percentages of self-evaluated HH compliance were as follows: (i) 76.9% for “Before touching a patient,” (ii) 85.8% for “Before clean/aseptic procedures,” (iii) 95.9% for “After body fluid exposure/risk,” (iv) 84.0% for “After touching a patient,” and (v) 69.2% for “After touching patient surroundings.” On the other hand, actual HH compliance was 11.7% for “Before touching a patient” and 18.0% for “After touching a patient or patient surroundings.” The present study demonstrated a big gap between self-evaluation and actual HH compliance among nurses working at hospitals, indicating the need of further providing the education in infection prevention.

DOI： 10.1177/17571774221094160

その他リンク： http://journals.sagepub.com/doi/full-xml/10.1177/17571774221094160

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells. 査読国際誌

Yoshiaki Soejima, Nahoko Iwata, Nanako Nakayama, Shinichi Hirata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Kohei Oguni, Takahiro Nada, Satoshi Fujisawa, Fumio Otsuka

International journal of molecular sciences 23 ( 17 ) 2022年8月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope LβT2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LHβ and FSHβ mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in LβT2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in LβT2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells.

DOI： 10.3390/ijms23179782

Site-specific differences in T lymphocyte composition of the gastric mucosa after Helicobacter pylori eradication. 査読国際誌

Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Makoto Abe, Hiroyuki Sakae, Yoshiyasu Kono, Hiromitsu Kanzaki, Takehiro Tanaka, Seiji Kawano, Fumio Otsuka, Yoshiro Kawahara, Hiroyuki Yanai, Hiroyuki Okada

Medicine 101 ( 34 ) e30241 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

In our earlier work, we revealed that inflammation of the lesser curvature of the gastric body and antrum could constitute independent risk factors for gastric cancer development, while inflammation of the greater curvature was not. The aims of this study were as follows: first, to reveal the differences between T lymphocyte populations of the gastric antrum and the greater and lesser curvatures of the gastric body in patients after Helicobacter pylori eradication; second, to analyze the correlation between the composition of the stomach-resident T lymphocytes and time from H. pylori eradication; and third, to evaluate the sex differences in T lymphocyte subsets after H. pylori eradication. To investigate site-specific differences in stomach-resident T lymphocytes after H. pylori eradication, we performed flow cytometry analysis on samples taken from the gastric antrum, greater curvature of the gastric body, and lesser curvature of the gastric body of 20 patients. We also analyzed the correlation between the composition of the stomach-resident T lymphocytes and the time from H. pylori eradication. The lymphocyte subsets of the antrum and lesser curvature of the body were similar. In contrast, compared to those in the greater curvature of the gastric body, CD4+/CD3+ lymphocyte subsets (43.8 ± 19.4% vs 31.7 ± 14.6%) were elevated in the lesser curvature of the body, whereas CD8+/CD3+ (67.1 ± 21.3% vs 80.4 ± 12.0%), CD7+/CD3+ (91.2 ± 4.6% vs 93.7 ± 3.8%), CCR4+/CD3+ (7.7 ± 8.1% vs 10.4 ± 7.0%), CD45RA+/CD3+CD4+ (27.2 ± 24.8% vs 39.5 ± 20.8%), and CD45RA+/CD3+CD4- (14.2 ± 11.1% vs 18.7 ± 11.5) were lower. Linear regression analysis showed a negative correlation between the time after H. pylori eradication and CD4+/CD3+ (P < .05, R2 = 0.198). There were no significant differences between men and women with respect to the lymphocyte populations. These results indicate that there are site-specific differences in lymphocyte composition in the stomach after H. pylori eradication.

DOI： 10.1097/MD.0000000000030241

Red blood cell depletion in small‐volume bone marrow processing using manipulation with third‐party red blood cells: A comparison of the performance of the COBE spectra and the spectra Optia systems 査読

Tuberculous aortic aneurysm developed with miliary tuberculosis. 査読国際誌

S Tanaka, H Hagiya, F Otsuka

QJM : monthly journal of the Association of Physicians 115 ( 8 ) 543 - 544 2022年8月

Yuichi Sumii, Nobuharu Fujii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 2022年8月

Global public awareness of Castleman disease and TAFRO syndrome between 2015 and 2021: A Google Trends analysis 査読

Yoshito Nishimura, Midori Filiz Nishimura, David C. Fajgenbaum, Frits van Rhee, Yasuharu Sato, Fumio Otsuka

eJHaem 3 ( 3 ) 748 - 753 2022年8月

Postprandial Reactive Hypoglycemia Detected with Premature Ventricular Contraction. 査読国際誌

Hiroyuki Honda, Shuichi Tanaka, Hideharu Hagiya, Fumio Otsuka

QJM : monthly journal of the Association of Physicians 115 ( 10 ) 675 - 676 2022年7月

Prevalence of psychological distress on public health officials amid COVID-19 pandemic. 査読国際誌

Yoshito Nishimura, Tomoko Miyoshi, Hideharu Hagiya, Fumio Otsuka

Asian journal of psychiatry 73 103160 - 103160 2022年7月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic has led to increased burnout among frontline healthcare workers (HCWs), little research has been done regarding the potential psychological burden among public health officials who have worked tirelessly to tackle the pandemic from an administrative perspective. This study aimed to determine the prevalence of burnout, depression, and job-related stress in Japanese public health officers amid the COVID-19 pandemic. METHODS: We conducted an anonymous, self-administered web-based cross-sectional survey including basic demographics, work-related questions, the Maslach Burnout Inventory, Patient Health Questionnaire-9, Utrecht Work Engagement Scale-3, and Brief Job Stress Questionnaire. 100 public health officers working in the public health centers (PHCs) in Okayama, Japan, answered the survey in December 2021 when the 5th surge in the number of COVID-19 was over. RESULTS: The prevalence of burnout, depression, and job-related stress was 27%, 43%, and 62%, respectively. The multivariate logistic analysis demonstrated that females, public health nurses, and those who suffered from a lack of support from their workplaces were significantly associated with psychological distress. CONCLUSIONS: While we tend to focus on mitigation plans to help alleviate burnout of frontline HCWs, more focus is needed to help public health officers, and public health nurses, in particular, to alleviate their psychological distress and job-related stress to prevent further staff shortages and secure sustainable health systems.

DOI： 10.1016/j.ajp.2022.103160

Vancomycin MIC creep progresses in methicillin-resistant Staphylococcus aureus despite the national antimicrobial stewardship campaign: Single facility data in Japan. 査読国際誌

Takumi Fujimori, Hideharu Hagiya, Koji Iio, Tsukasa Higashionna, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 ( 7 ) 918 - 922 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial and community infections, and vancomycin (VCM) is widely recommended as a first-line therapeutic drug. Minimum inhibitory concentrations (MICs) of VCM ≤2 μg/mL are defined as susceptible, but increases in these levels, known as "VCM MIC creep" have been reported. The aim of this study was to investigate VCM MIC creep during the promotion of a national antimicrobial stewardship campaign. METHODS: We collected data from 2013 to 2020 on S. aureus isolated at the clinical microbiology laboratory at Okayama University Hospital, Japan. We calculated the annual proportions of MRSA isolation rates by MIC levels for nosocomial and community samples and estimated annual percentage changes in the antimicrobial use density of the VCM. RESULTS: Of the 1,716 MRSA isolates, no strains showed intermediate or resistant ranges of VCM MIC levels. By 2020, the proportion of MRSA with an MIC of ≤0.5 μg/mL decreased to 35.4%, while that with an MIC of 1 μg/mL increased to 64.1% over time. The annual percentage changes of the VCM antimicrobial use density significantly increased without any trend change point (average 8.1%, p = 0.035). There was no clear correlation between the VCM AUD and annual proportion of nosocomial MRSA with MIC 1 μg/mL (correlation coefficient 0.48; p value = 0.24). CONCLUSION: We demonstrated a deteriorating situation of VCM MIC creep among MRSA strains isolated at our university hospital during the national antimicrobial stewardship campaign.

DOI： 10.1016/j.jiac.2022.03.017

Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people 査読

Hideharu Hagiya, Takao Hikita, Tomohiro Habu, Masaki Asada, Takashi Yorifuji, Shinichi Toyooka, Fumio Otsuka, Masanori Nakayama

Journal of Infection 85 ( 4 ) 436 - 480 2022年7月

Persistent methicillin-resistant Staphylococcus aureus bacteremia in an adult patient with Netherton's syndrome: A case report 査読

Misa Takahashi, Hideharu Hagiya, Shuichi Tanaka, Koichiro Yamamoto, Hiroyuki Honda, Kou Hasegawa, Fumio Otsuka

Journal of Infection and Chemotherapy 28 ( 7 ) 978 - 981 2022年7月

Primary bone lymphoma presenting as fever of unknown origin 査読

Yuki Otsuka, Yasuhiro Nakano, Daisuke Omura, Kou Hasegawa, Fumio Otsuka

Journal of General and Family Medicine 23 ( 4 ) 280 - 281 2022年7月

「哲学カフェ」は医師のどのような能力を涵養するか

小比賀美香子, 松川えり, 徳増一樹, 大塚文男

医学教育 53 ( Suppl. ) 145 - 145 2022年7月

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID. 査読国際誌

Kazuki Tokumasu, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Koichiro Yamamoto, Yasuhiro Nakano, Toru Hasegawa, Yukichika Yamamoto, Yuki Otsuka, Hideharu Hagiya, Hitomi Kataoka, Keigo Ueda, Fumio Otsuka

Medicina (Kaunas, Lithuania) 58 ( 7 ) 2022年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

DOI： 10.3390/medicina58070850

Clinical characteristics and outcomes of IgG4-positive marginal zone lymphoma: Systematic scoping review. 査読国際誌

Yoshito Nishimura, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Fumio Otsuka

Pathology international 2022年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Immunoglobulin G4 (IgG4)-positive marginal zone lymphoma (MZL) is rare and undefined. It is unclear whether IgG4-positive MZLs have as favorable an outcome as MZLs in general. Also, correlation with IgG4-related disease (IgG4-RD) and IgG4-positive MZLs is unknown. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"IgG4" and "marginal zone lymphoma" from their inception to February 20, 2022. Twenty-two articles, including six observational studies and 24 cases from 16 case reports and case series, were included. Only one study had a comparative group, and the other five were exploratory observational studies. IgG4-positive MZLs commonly occurred in males (83.3%). It primarily involved ocular adnexa (41.7%) and skin (29.2%). Only 29.2% had concurrent IgG4-RD, and no expiration was noted. While most cases were treated with excision, resection, or clinical observation, 21.7% received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone as a first-line treatment. This systematic review summarizes the current understanding of the characteristics of IgG4-positive MZLs. While there seems to be IgG4-RD-related and de novo IgG4-positive MZLs, future research needs to clearly define MZL with polyclonal IgG4-positive cells and IgG4-producing lymphoma. Further studies are critical to clarifying long-term prognosis and optimal surveillance planning.

DOI： 10.1111/pin.13251

「筋痛性脳脊髄炎/慢性疲労症候群(ME/CFS)」岡山大学病院総合内科・総合診療科におけるME/CFS診療

片岡仁美, 大塚勇輝, 本多寛之, 砂田匠彦, 櫻田泰江, 松田祐依, 徳増一樹, 長谷川功, 小比賀美香子, 植田圭吾, 大塚文男

日本疲労学会誌 18 ( 1 ) 37 - 37 2022年6月

Eyelid edema due to Cushing's syndrome 査読国際誌

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Clinical Case Reports 10 ( 6 ) e05940 2022年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Cushing's syndrome (CS) shows diverse signs such as centripetal obesity, moon face, and buffalo hump, which can complicate the diagnosis. Facial features including eyelid edema, as an underrecognized sign, can be diagnostic clues for an excess of corticoids in a CS patient.

DOI： 10.1002/ccr3.5940

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.5940

「筋痛性脳脊髄炎/慢性疲労症候群(ME/CFS)」岡山大学病院総合内科・総合診療科におけるME/CFS診療

片岡仁美, 大塚勇輝, 本多寛之, 砂田匠彦, 櫻田泰江, 松田祐依, 徳増一樹, 長谷川功, 小比賀美香子, 植田圭吾, 大塚文男

日本疲労学会誌 18 ( 1 ) 37 - 37 2022年6月

胸鎖関節炎・頸部膿瘍を契機に診断した2型糖尿病の1例

中本健太, 本多寛之, 平佑貴, 庵谷紘美, 中野靖浩, 長谷川功, 萩谷英大, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 65 ( 6 ) 337 - 337 2022年6月

維持透析中の2型糖尿病患者に発症したフルニエ壊疽の1例

庵谷紘美, 本多寛之, 平佑貴, 中本健太, 中野靖浩, 長谷川功, 萩谷英大, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 65 ( 6 ) 337 - 337 2022年6月

医学生の自覚ストレスとコミュニケーションの関連横断研究

徳増一樹, 西村義人, 坂本陽子, 小比賀美香子, 片岡仁美, 大塚文男

日本プライマリ・ケア連合学会学術大会 13回 O - 90 2022年6月

「筋痛性脳脊髄炎/慢性疲労症候群(ME/CFS)」漢方によるlong COVIDの倦怠感への対応

徳増一樹, 植田圭吾, 大塚勇輝, 本多寛之, 砂田匠彦, 櫻田泰江, 松田祐依, 片岡仁美, 大塚文男

日本疲労学会誌 18 ( 1 ) 37 - 37 2022年6月

維持透析中の2型糖尿病患者に発症したフルニエ壊疽の1例

庵谷紘美, 本多寛之, 平佑貴, 中本健太, 中野靖浩, 長谷川功, 萩谷英大, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 65 ( 6 ) 337 - 337 2022年6月

胸鎖関節炎・頸部膿瘍を契機に診断した2型糖尿病の1例

中本健太, 本多寛之, 平佑貴, 庵谷紘美, 中野靖浩, 長谷川功, 萩谷英大, 小比賀美香子, 片岡仁美, 大塚文男

糖尿病 65 ( 6 ) 337 - 337 2022年6月

Application of Kampo Medicines for Treatment of General Fatigue Due to Long COVID. 査読国際誌

Kazuki Tokumasu, Keigo Ueda, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Yasuhiro Nakano, Toru Hasegawa, Yuki Otsuka, Mikako Obika, Hideharu Hagiya, Hitomi Kataoka, Fumio Otsuka

Medicina (Kaunas, Lithuania) 58 ( 6 ) 2022年5月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Evidence regarding treatment for the acute phase of COVID-19 has been accumulating, but specific treatment for long COVID/post-COVID-19 condition has not yet been established. Treatment with herbal medicine might be one treatment option for long COVID, but there has been little research on the effectiveness of herbal medicine for long COVID. The aim of this study was to clarify the prescription patterns of Kampo medicines, which are herbal medicines that originated in China and were developed in Japan, for the treatment of general fatigue due to long COVID. A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period from Feb 2021 to Dec 2021 with a focus on symptoms accompanying general fatigue and prescriptions of Kampo medicine. Among the clinical data obtained from medical records of 195 patients, clinical data for 102 patients with general fatigue and accompanying symptoms were analyzed. The patients had various symptoms, and the most frequent symptoms accompanying general fatigue were dysosmia, dysgeusia, headache, insomnia, dyspnea, and hair loss. Prescriptions of Kampo medicine accounted for 24.1% of the total prescriptions (n = 609). The most frequently prescribed Kampo medicine was hochuekkito (71.6%) and other prescribed Kampo medicines were tokishakuyakusan, ryokeijutsukanto, juzentaihoto, hangekobokuto, kakkonto, ninjin'yoeito, goreisan, rikkunshito, and keishibukuryogan. Since the pathophysiology of general fatigue after an infectious disease is, in general, considered a qi deficiency in Kampo medicine, treatments with such compensation agents can be the major prescription as a complement for the qi. In conclusion, Kampo medicine can be one of the main pharmacological treatments for long COVID accompanying general fatigue.

DOI： 10.3390/medicina58060730

Characterization of Gastric Tissue-Resident T Cells in Autoimmune and Helicobacter pylori-Associated Gastritis 査読国際誌

Daisuke Kametaka, Masaya Iwamuro, Takahide Takahashi, Araki Hirabata, Kenta Hamada, Yoshiyasu Kono, Hiromitsu Kanzaki, Seiji Kawano, Takehiro Tanaka, Fumio Otsuka, Yoshiro Kawahara, Hiroyuki Okada

Current Issues in Molecular Biology 44 ( 6 ) 2443 - 2452 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Data regarding the in-depth surface marker profiles of gastric tissue-resident lymphocytes in autoimmune and Helicobacter pylori-associated gastritis are lacking. In this study, we investigated potential differences in lymphocyte composition between these profiles. We enrolled patients with autoimmune (n = 14), active (current infection of H. pylori in the stomach; n = 10), and inactive gastritis (post-eradication of H. pylori; n = 20). Lymphocytes were isolated from the greater curvature of the stomach and lesser curvature of the body and analyzed using flow cytometry. The CD8+/CD3+ and CD4+/CD3+ ratios differed between the samples. Body CD4+/antrum CD4+, which is calculated by dividing the CD4+/CD3+ ratio in the body by that in the antrum, was significantly higher in autoimmune gastritis (3.54 ± 3.13) than in active (1.47 ± 0.41) and inactive gastritis (1.42 ± 0.77). Antrum CD8+/CD4+ in autoimmune gastritis (7.86 ± 7.23) was also higher than that in active (1.49 ± 0.58) and inactive gastritis (2.84 ± 2.17). The area under the receiver operating characteristic curve of antrum CD8+/CD4+ was 0.842, and the corresponding optimal cutoff point was 4.0, with a sensitivity of 71.4% and a specificity of 93.3%. We propose that an antrum CD8+/CD4+ ratio > 4.0 is a potential diagnostic marker for autoimmune gastritis.

DOI： 10.3390/cimb44060167

Call for correction: Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. 査読国際誌

Hideharu Hagiya, Yuki Otsuka, Fumio Otsuka

Journal of the neurological sciences 436 120232 - 120232 2022年5月

Adrenal and Testicular Tumor Formation Due to 21-Hydroxylase Deficiency. 査読国際誌

Koichiro Yamamoto, Hiroyuki Honda, Fumio Otsuka

The American journal of medicine 135 ( 5 ) e106 2022年5月

Inconsistency of the "Sogo-Shinryo" department in Japanese hospitals. 査読

Yuki Otsuka, Mikako Obika, Fumio Otsuka

Journal of general and family medicine 23 ( 3 ) 201 - 202 2022年5月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

The inconsistency of Japanese names of "Sogo-Shinryo" departments is also a greater problem in this country, and we are afraid that it may cause anxiety to patients, residents, and students. As one of the "Sogo-Shinryo" departments in Japan, we want to provide them comprehensive learning environments regardless of the boundaries of academic cliques and societies, and, as a result, relieve them, foster general minds, and build their careers.

DOI： 10.1002/jgf2.522

Trends in sarcoidosis mortality rate in Japan from 2001 to 2020: A population-based study 査読国際誌

Ko Harada, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Respiratory Medicine 196 106828 - 106828 2022年5月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

BACKGROUND: The sarcoidosis mortality rate has increased over the years, which contributes to the health care burden. Although epidemiological studies of sarcoidosis mortality in aging societies are essential, none have been published since 1989 in Japan. METHODS: We aimed to investigate the trends in crude and age-adjusted sarcoidosis-associated mortality rates per 1,000,000 population in Japan from 2001 to 2020 using national death certificate data among older adults aged over 50 years. The data were analysed using the joinpoint regression models to estimate long-term trends and average annual percentage changes (AAPCs). RESULTS: A total of 3094 sarcoidosis-associated deaths were recorded from 2001 to 2020 in Japan; women constituted 65.3% of these, with a female:male ratio of 1.89. Nearly 80% of deaths were over the age of 65 years, of which 32% were over the age of 80 years. The trend in crude mortality of those aged ≥80 years markedly increased from 0.81 to 9.68 per 1,000,000 population in men and from 2.38 to 12.87 in women, respectively. The overall age-adjusted sarcoidosis mortality rate increased 2.46-fold during the study period, with an AAPC of 5.1%. CONCLUSIONS: This study revealed that sarcoidosis-associated deaths in Japan have significantly increased over the past two decades, especially among the older population with a female predominance. Given the rising mortality rate and susceptibility of the older population, sarcoidosis will require more attention from health care providers in terms of a multidisciplinary approach to address the specific needs of the older population.

DOI： 10.1016/j.rmed.2022.106828

甲状腺機能低下症によるPsychosis（Myxedema Psychosis）の臨床的特徴―症例報告と文献レビュー― 査読

山田裕士, 藤原雅樹, 宋龍平, 枝廣暁, 深尾貴志, 酒本真次, 高東祥一朗, 川田清宏, 和迩健太, 山本紘一郎, 大塚文男, 山田了士

精神神経学雑誌 124 ( 5 ) 293 - 299 2022年5月

記述言語：日本語出版者・発行元：(公社)日本精神神経学会

精神症状を呈した甲状腺機能低下症の患者の15%が精神病症状を生じると報告されており,「myxedema psychosis」と呼ばれる.しかし,わが国の精神科領域での報告は数例にとどまり,十分に認知されていない可能性がある.そこで,本症例報告では,精神科におけるmyxedema psychosis鑑別の重要性を改めて強調するため,自験例の詳細な臨床像を記述したうえで,系統的レビューで得られた症状,検査所見,治療経過の特徴を整理して呈示する.症例は50歳代の女性.X-2年に橋本病と診断され,レボチロキシンで治療されていた.X年5月にレボチロキシンを自己中断後,徐々に過敏になり,幻聴に左右されて家を飛びだすようになった.同月末に不安と動悸症状でA病院を受診し,著明な甲状腺機能低下が認められたため,内科に入院した.レボチロキシンを再開し,リスペリドンも開始されたが,精神病症状の改善に乏しく,精査を拒否するため,入院第7病日に当院当科へ転院した.転院時,幻聴は改善していたが,思路障害や焦燥は残存し,甲状腺機能低下も持続していた.脳波検査では徐波が混入しており,髄液検査ではタンパクの軽度高値を認めたことから,橋本脳症の可能性も考えたが,症状が改善傾向であったため,ステロイド投与は保留し,レボチロキシンを増量し経過観察した.すると,転院第7病日までに精神病症状は消失し,転院第16病日に退院した.12月にリスペリドンを中止後も精神病症状の再燃はなかった.X+1年8月にTSHの上昇とともに精神病症状が再発したが,レボチロキシンの増量により速やかに症状は改善した.Myxedema psychosisは甲状腺ホルモン補充により抗精神病薬中止が可能と系統的レビューが示すように,本症例もレボチロキシンの補充で症状は速やかに改善した.Myxedema psychosisは抗精神病薬の中止が可能な予後良好な病態であるため,精神病症状を呈した患者の治療においては,甲状腺機能の評価を行うことが望ましい.(著者抄録)

Processes of increasing medical residents' intrinsic motivation: a qualitative study. 査読国際誌

Kazuki Tokumasu, Mikako Obika, Haruo Obara, Makoto Kikukawa, Yoshito Nishimura, Fumio Otsuka

International journal of medical education 13 115 - 123 2022年4月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Objectives: This study aimed to determine qualitatively how medical residents develop intrinsic motivation to learn and work in clinical training settings. Methods: This study was a descriptive qualitative study, which is widely used in healthcare research. We conducted a semi-structured interview aimed to explore key participants' in-depth experiences and perspectives regarding intrinsic motivation. The authors interviewed seven postgraduate Japanese medical residents. The transcripts were analyzed using the sequential and thematic qualitative data analysis technique steps for coding and theorization, which entails coding steps from open to selective, writing a storyline using the final selective codes, and offering theories. Results: External stimulations (a self-handle environment and a near-peer role model) triggered the medical residents' cognitive process (gap recognition, awareness, and internalization) to intrinsic motivation. The residents' awareness of autonomy, responsibility, and independence played a vital role in this process. Furthermore, a psychological feeling of competence also reinforced their intrinsic motivation. Positive feedback and approval from attending physicians and patients' gratitude promoted residents' sense of competence. Conclusions: We illustrated a process for increasing medical residents' intrinsic motivation. The intrinsic motivation was triggered by external stimulations (a self-handle environment and a near-peer role model), which caused the cognitive process: gap recognition, awareness of important attitudes as a doctor (autonomy, responsibility, and independence), and internalization. Since the first step of this process was an external factor, there are potential benefits of designing an appropriate training environment for increasing medical residents' intrinsic motivation.

DOI： 10.5116/ijme.6250.1017

Global public awareness of Castleman disease and TAFRO syndrome between 2015 and 2021: A Google Trends analysis 査読

Yoshito Nishimura, Midori Filiz Nishimura, David C. Fajgenbaum, Frits van Rhee, Yasuharu Sato, Fumio Otsuka

eJHaem 3 ( 3 ) 748 - 753 2022年4月

Hormonal trends in patients suffering from long COVID symptoms. 査読

Naruhiko Sunada, Hiroyuki Honda, Yasuhiro Nakano, Koichiro Yamamoto, Kazuki Tokumasu, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Yuki Otsuka, Mikako Obika, Yoshihisa Hanayama, Hideharu Hagiya, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Endocrine journal 69 ( 10 ) 1173 - 1181 2022年4月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.

DOI： 10.1507/endocrj.EJ22-0093

Late-Onset Hypogonadism in a Male Patient with Long COVID Diagnosed by Exclusion of ME/CFS. 査読国際誌

Yoshiaki Soejima, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Ko Harada, Kenta Nakamoto, Naruhiko Sunada, Yasue Sakurada, Kou Hasegawa, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Medicina (Kaunas, Lithuania) 58 ( 4 ) 2022年4月

担当区分：最終著者記述言語：英語

After the acute phase of COVID-19, some patients have been reported to have persistent symptoms including general fatigue. We have established a COVID-19 aftercare clinic (CAC) to provide care for an increasing number of these patients. Here, we report the case of a 36-year-old man who developed post-COVID fatigue after acute infection with SARS-CoV-2. In the acute phase of COVID-19, the patient's fever resolved within four days; however, general fatigue persisted for three months, and he visited our CAC 99 days after the initial infection. Examination revealed a high Aging Male's Symptoms (AMS) score of 44 and low free testosterone (FT) level of 5.5 pg/mL, which meet the Japanese criteria of late-onset hypogonadism (LOH) syndrome. Imaging studies revealed an atrophic pituitary in addition to fatty liver and low bone mineral density. Anterior pituitary function tests showed a low follicle-stimulating hormonelevel and delayed reaction of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation, indicating the possibility of hypothalamic hypogonadism in addition to primary hypogonadism seen in patients with post-COVID-19 conditions. After the initiation of Japanese traditional medicine (Kampo medicine: hochuekkito followed by juzentaihoto), the patient's symptoms as well as his AMS score and serum FT level were noticeably improved. Furthermore, follow-up tests of GnRH stimulation revealed improvements in LH responsiveness. Although many patients have been reported to meet the criteria of ME/CFS such as our case, we emphasize the possibility of other underlying pathologies including LOH syndrome. In conclusion, LOH syndrome should be considered a cause of general fatigue in patients with post-COVID-19 conditions and herbal treatment might be effective for long COVID symptoms due to LOH (264 words).

DOI： 10.3390/medicina58040536

Antimicrobial prescription practices for outpatients with uncomplicated cystitis in Japan. 査読国際誌

Misa Takahashi, Hideharu Hagiya, Tsukasa Higashionna, Yasuhiro Nakano, Kota Sato, Yuto Haruki, Mai Haruki, Hiroyuki Honda, Hiroko Ogawa, Keigo Ueda, Fumio Otsuka

Scientific reports 12 ( 1 ) 5921 - 5921 2022年4月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

To promote antimicrobial stewardship, we studied antimicrobial prescription rates for uncomplicated cystitis, a common outpatient disease requiring antibiotic treatment. This multicenter retrospective study was performed from January 1, 2018, to December 31, 2020, in Japan, targeting outpatients aged ≥ 20 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting uncomplicated cystitis (N300). The data of 1445 patients were collected and that of 902 patients were analyzed. The overall median patient age was 71 years and a proportion of those aged less than 50 years was 18.8% with a female dominance (82.6%). Antimicrobials were prescribed for 884 patients (98.0%) and a total of 623 patients (69.1%) were treated with broad-spectrum drugs, including fluoroquinolones (36.0%), third-generation cephalosporins (29.9%) and faropenem (3.1%). A logistic regression model revealed that the broad-spectrum agents were significantly prescribed for the older patients, male patients, and those who visited internists. Recurrence was observed in 37 (4.1%) cases, and the multivariate analysis suggested any of age, sex, or antimicrobial types were not associated with the recurrence. Collectively, approximately two-thirds of antimicrobials prescribed for uncomplicated cystitis were broad-spectrum agents. The present data would be an indicator for antimicrobial prescriptions in uncomplicated cystitis in Japan.

DOI： 10.1038/s41598-022-09946-8

Relationship between patients’ characteristics and efficacy of calcimimetics for primary hyperparathyroidism in the elderly

Koichiro Yamamoto, Yasuhiro Nakano, Kazuki Tokumasu, Hiroyuki Honda, Kou Hasegawa, Asuka Sato, Hiroko Ogawa, Mikako Obika, Yoshihisa Hanayama, Fumio Otsuka

Clinical Case Reports 10 ( 4 ) 2022年4月

Cat scratch disease without a history of cat exposure 国際誌

Kosuke Oka, Yume Takagi, Hideharu Hagiya, Fumio Otsuka

Clinical Case Reports 10 ( 4 ) e04816 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

A patient complaining of swelling and tenderness in her left axilla was diagnosed with cat scratch disease despite no apparent history of cat exposure. Zoonosis can occur even in the absence of cat exposure because cat flea Ctenocephalides felis is also the vector of the pathogen through the flea feces.

DOI： 10.1002/ccr3.4816

原発性副甲状腺機能亢進症に対するカルシウム受容体作動薬の効果と関連因子

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.4816

Half-and-Half Toenails

Koichiro Yamamoto, Fumio Otsuka

Mayo Clinic Proceedings 97 ( 4 ) 652 - 652 2022年4月

IFN-α投与が奏効したステロイド抵抗性Erdheim-Chester病の1例

庵谷紘美, 中野靖浩, 中本健太, 平佑貴, 山本紘一郎, 長谷川功, 三好智子, 小川弘子, 白羽英則, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 279 - 279 2022年4月

COVID-19後遺症契機に発見された2型糖尿病の1例

田中秀一, 本多寛之, 山本絋一郎, 高橋美砂, 長谷川功, 小比賀美香, 片岡仁美, 大塚文男

糖尿病 65 ( Suppl.1 ) S - 268 2022年4月

山本紘一郎, 中野靖浩, 徳増一樹, 本多寛之, 長谷川功, 小比賀美香子, 三好智子, 小川弘子, 花山宜久, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 374 - 374 2022年4月

重度の化膿性胸鎖関節炎から発見された2型糖尿病の1例

高瀬了輔, 本多寛之, 中本健太, 平佑貴, 庵谷紘美, 中野靖浩, 長谷川功, 萩谷英大, 小比賀美香子, 片岡仁美, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 363 - 363 2022年4月

Cushing病術後にバセドウ病再燃と相対的副腎不全を来した1例

中野靖浩, 平佑貴, 中本健太, 庵谷紘美, 長谷川功, 大塚勇輝, 佐々木恵里佳, 岸田雅之, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 346 - 346 2022年4月

体動困難を契機に発見され副腎クリーゼを発症したACTH単独欠損症の1例

中野靖浩, 中本健太, 平佑貴, 庵谷紘美, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 336 - 336 2022年4月

頭部外傷が契機と考えられる中枢性尿崩症の1例

山本紘一郎, 本多寛之, 田中秀一, 高橋美砂, 長谷川功, 中野靖浩, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 335 - 335 2022年4月

肝硬変と多発骨折を契機に診断されたFGF23関連低リン血症性骨軟化症の1例

須山敦仁, 山本紘一郎, 田中秀一, 孫麗那, 高橋美砂, 中野靖浩, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 325 - 325 2022年4月

経過中に難治性高血圧症を合併した血管型Ehlers-Danlos症候群の1例

長谷川功, 田中秀一, 山本紘一郎, 中野靖浩, 本多寛之, 萩谷英大, 冨田晃司, 戸田洋伸, 内田治仁, 平沢晃, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 322 - 322 2022年4月

コロナ・アフターケア(CAC)外来における後遺症の特徴と抗体価との関連

櫻田泰江, 砂田匠彦, 大塚勇輝, 徳増一樹, 中野靖浩, 本多寛之, 松田祐依, 大村大輔, 長谷川功, 萩谷英大, 小比賀美香子, 植田圭吾, 片岡仁美, 古川雅規, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 301 - 301 2022年4月

精巣副腎遺残腫瘍に関連し性腺機能低下を来した21-水酸化酵素欠損症の2例

山本紘一郎, 本多寛之, 中野靖浩, 徳増一樹, 長谷川功, 小比賀美香子, 花山宜久, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 401 - 401 2022年4月

精巣副腎遺残腫瘍に関連し性腺機能低下を来した21-水酸化酵素欠損症の2例

山本紘一郎, 本多寛之, 中野靖浩, 徳増一樹, 長谷川功, 小比賀美香子, 花山宜久, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 401 - 401 2022年4月

原発性副甲状腺機能亢進症に対するカルシウム受容体作動薬の効果と関連因子

山本紘一郎, 中野靖浩, 徳増一樹, 本多寛之, 長谷川功, 小比賀美香子, 三好智子, 小川弘子, 花山宜久, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 374 - 374 2022年4月

頭部外傷が契機と考えられる中枢性尿崩症の1例

山本紘一郎, 本多寛之, 田中秀一, 高橋美砂, 長谷川功, 中野靖浩, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 335 - 335 2022年4月

LβT2細胞におけるオレキシンとBMPによるゴナドトロピン分泌調節の検討

副島佳晃, 岩田菜穂子, 中山菜々子, 平田真一, 中野靖浩, 山本紘一郎, 須山敦仁, 灘隆宏, 藤澤諭, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 329 - 329 2022年4月

肝硬変と多発骨折を契機に診断されたFGF23関連低リン血症性骨軟化症の1例

須山敦仁, 山本紘一郎, 田中秀一, 孫麗那, 高橋美砂, 中野靖浩, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 325 - 325 2022年4月

コロナ・アフターケア外来における加齢性腺機能低下(LOH)症候群の潜在とその特徴

山本幸近, 大塚勇輝, 徳増一樹, 中野靖浩, 本多寛之, 櫻田泰江, 砂田匠彦, 大村大輔, 長谷川功, 萩谷英大, 小比賀美香子, 植田圭吾, 片岡仁美, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 292 - 292 2022年4月

骨粗鬆症精査を契機に診断されたTurner症候群の1成人例

長谷川徹, 越智可奈子, 中野靖浩, 山本紘一郎, 小比賀美香子, 植田圭吾, 長谷川高誠, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 402 - 402 2022年4月

LβT2細胞におけるオレキシンとBMPによるゴナドトロピン分泌調節の検討

副島佳晃, 岩田菜穂子, 中山菜々子, 平田真一, 中野靖浩, 山本紘一郎, 須山敦仁, 灘隆宏, 藤澤諭, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 329 - 329 2022年4月

IFN-α投与が奏効したステロイド抵抗性Erdheim-Chester病の1例

庵谷紘美, 中野靖浩, 中本健太, 平佑貴, 山本紘一郎, 長谷川功, 三好智子, 小川弘子, 白羽英則, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 279 - 279 2022年4月

Cushing病術後にバセドウ病再燃と相対的副腎不全を来した1例

中野靖浩, 平佑貴, 中本健太, 庵谷紘美, 長谷川功, 大塚勇輝, 佐々木恵里佳, 岸田雅之, 大塚文男

日本内分泌学会雑誌 98 ( 1 ) 254 - 254 2022年4月

ADHDの薬物治療強化により減量と血糖コントロールの改善が得られた若年肥満男性の1例

本多寛之, 大塚文男

糖尿病 65 ( Suppl.1 ) S - 233 2022年4月

Detection of Male Hypogonadism in Patients with Post COVID-19 Condition. 国際誌

Yukichika Yamamoto, Yuki Otsuka, Naruhiko Sunada, Kazuki Tokumasu, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Hideharu Hagiya, Yoshihisa Hanayama, Fumio Otsuka

Journal of clinical medicine 11 ( 7 ) 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that "general fatigue" mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients' backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT < 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = -0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID.

DOI： 10.3390/jcm11071955

Low hematocrit reduces the efficiency of <scp>CD34</scp> ⁺ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure

Takumi Kondo, Nobuharu Fujii, Keiko Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 2022年3月

Hemothorax and Bloody Ascites Caused by Vascular Ehlers-Danlos Syndrome. 国際誌

Shuichi Tanaka, Hiroyuki Honda, Kou Hasegawa, Koji Tomita, Reimi Sogawa, Hideki Yamamoto, Takao Hiraki, Akira Hirasawa, Fumio Otsuka

The American journal of medicine 135 ( 7 ) e210-e211 2022年3月

Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease?

Yoshito Nishimura, Asami Nishikori, Haruki Sawada, Torrey Czech, Yuki Otsuka, Midori Filiz Nishimura, Hiroki Mizuno, Naoki Sawa, Shuji Momose, Kumiko Ohsawa, Fumio Otsuka, Yasuharu Sato

Journal of clinical and experimental hematopathology : JCEH 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies. Among 63 iMCD patients in our database, 19 were positive for at least one autoantibody. Among the 19, we identified five with plasma cell type (PC)-iMCD lymph node histopathology and positive anti-phospholipid antibodies. These patients were likely to have thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, organomegaly (TAFRO) symptoms, and thrombotic events. The present study suggests that patients with undiagnosed or atypical autoimmune diseases, including anti-phospholipid syndrome (APS), were treated for iMCD. APS may present with thrombocytopenia or even multi-organ failure, which overlap with clinical presentations of iMCD. Due to differences in the treatment regimen and follow-up, recognition of the undiagnosed autoimmune disease process in those suspected of iMCD is essential. Our study highlights the importance of complete exclusion of differential diagnoses in patients with iMCD in their diagnostic workup.

DOI： 10.3960/jslrt.21038

初期研修医の卒後ローテーションにおける「感染症研修の必須化」に関するアンケート調査

萩谷英大, 徳増一樹, 小比賀美香子, 大塚文男

感染症学雑誌 96 ( 2 ) 61 - 64 2022年3月

Trends in the amyloidosis mortality rate in <scp>J</scp> apan: A nationwide observational study from 1998 to 2019

Ko Harada, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Geriatrics & Gerontology International 22 ( 3 ) 246 - 250 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

AIM: Despite the increasing attention that has been paid to amyloidosis in recent years, there have been few reports on amyloidosis mortality and its trends worldwide. This study aimed to evaluate the trends in crude and age-adjusted amyloidosis-associated mortality rates in Japan from 1998 to 2019. METHODS: We used national Vital Statistics data among older adults aged over 50 years. The data were analyzed using the joinpoint regression program to estimate the long-term trends and average annual percentage changes (AAPCs). RESULTS: A total of 9158 amyloidosis-associated deaths were recorded from 1998 to 2019, of which 56.1% were in men. The crude mortality rate per 1 000 000 older adults aged over 80 years increased from 9.65 to 54.3 among men and from 7.02 to 22.1 among women during the study period. Overall, the AAPCs of age-adjusted amyloidosis-associated mortality rates increased significantly over the study period (1.8%, 95% confidence interval [CI], 1.0-2.7%). While the annual percentage change (APC) of age-adjusted mortality rates in women showed no significant change over the study period, the APC in men markedly increased in the 2013-2019 period (8.2%, 95% CI: 6.0-10.4%). CONCLUSIONS: This study revealed an increasing trend in mortality associated with amyloidosis, and in particular a marked increase in mortality among men over the past 6 years. Considering its high mortality rate and susceptibility to the effects of an increasing population of older adults, amyloidosis deserves more attention from healthcare providers to improve the understanding of diagnosis, clinical treatment, and healthcare planning. Geriatr Gerontol Int 2022; 22: 246-250.

DOI： 10.1111/ggi.14348

卵胞ステロイド合成におけるNR5Aの役割とClock・BMPによる調節機序

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ggi.14348

須山敦仁, 岩田菜穂子, 副島佳晃, 中野靖浩, 山本紘一郎, 灘隆宏, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1303 - 1303 2022年3月

非機能性下垂体腺腫を伴った偽性クッシング症候群の1例

山本紘一郎, 花山宜久, 中野靖浩, 大村大輔, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1262 - 1262 2022年3月

不明熱の精査より診断した高齢特発性ACTH単独欠損症の1例

上枝礼佳, 山本紘一郎, 田中秀一, 孫麗那, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1261 - 1261 2022年3月

ゴナドトロープ細胞における時計遺伝子およびBMP分子の機能的役割

副島佳晃, 岩田菜穂子, 須山敦仁, 中野靖浩, 山本紘一郎, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1247 - 1247 2022年3月

潜在性甲状腺機能低下症の総合診療外来における検出とその特徴

高見優男, 山本紘一郎, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1143 - 1143 2022年3月

コロナ・アフターケア外来から診断されたLOH症候群の1例

副島佳晃, 中野靖浩, 徳増一樹, 大塚勇輝, 櫻田泰江, 本多寛之, 中本健太, 長谷川功, 萩谷英大, 植田圭吾, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1304 - 1304 2022年3月

非機能性下垂体腺腫を伴った偽性クッシング症候群の1例

山本紘一郎, 花山宜久, 中野靖浩, 大村大輔, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1262 - 1262 2022年3月

不明熱の精査より診断した高齢特発性ACTH単独欠損症の1例

上枝礼佳, 山本紘一郎, 田中秀一, 孫麗那, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1261 - 1261 2022年3月

潜在性甲状腺機能低下症の総合診療外来における検出とその特徴

高見優男, 山本紘一郎, 中野靖浩, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1143 - 1143 2022年3月

摂食調節ホルモンによる卵胞ステロイド合成への影響とその機序の検討

中野靖浩, 樫野千明, 長谷川徹, 岩田菜穂子, 副島佳晃, 須山敦仁, 山本紘一郎, 増山寿, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1363 - 1363 2022年3月

卵胞ステロイド合成におけるNR5Aの役割とClock・BMPによる調節機序

須山敦仁, 岩田菜穂子, 副島佳晃, 中野靖浩, 山本紘一郎, 灘隆宏, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1303 - 1303 2022年3月

ゴナドトロープ細胞における時計遺伝子およびBMP分子の機能的役割

副島佳晃, 岩田菜穂子, 須山敦仁, 中野靖浩, 山本紘一郎, 大塚文男

日本内分泌学会雑誌 97 ( 5 ) 1247 - 1247 2022年3月

初期研修医の卒後ローテーションにおける「感染症研修の必須化」に関するアンケート調査

萩谷英大, 徳増一樹, 小比賀美香子, 大塚文男

感染症学雑誌 96 ( 2 ) 61 - 64 2022年3月

記述言語：日本語出版者・発行元：(一社)日本感染症学会

初期研修医の卒後ローテーションにおける「感染症研修の必須化」に関する意識などを明らかにすることを目的に、岡山県内で初期研修プログラムを有する16の研修病院に所属する初期研修医(卒後1・2年)、および専攻医(卒後3・4・5年)を対象にウェブ・アンケートを行い、127名(男性64名、女性60名、無回答3名)より回答を得た。その結果、初期研修医制度における「感染症研修の必須化」(例:最低1ヵ月ローテーションするなど)について84名(66.1%)が賛成すると回答した。一方、18名(14.2%)は必須化に反対しており、その理由として、「ローテーション選択の自由度を損なうため」(15名)などが挙げられた。

その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00276&link_issn=&doc_id=20220406400006&doc_link_id=1390010292792199424&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390010292792199424&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

成人複雑先天性心疾患患者における両心室修復術後の腎内血行動態が臨床状態に及ぼす影響(Impact of Intrarenal Hemodynamics on Clinical Status in Adults with Complex Congenital Heart Disease after Biventricular Repair)

武本梨佳, 杜徳尚, 高谷陽一, 横濱ふみ, 中山理絵, 赤木禎治, 内田治仁, 大塚文男, 伊藤浩

日本循環器学会学術集会抄録集 86回 MPJ08 - 1 2022年3月

Serial Changes of Long COVID Symptoms and Clinical Utility of Serum Antibody Titers for Evaluation of Long COVID. 国際誌

Yasue Sakurada, Naruhiko Sunada, Hiroyuki Honda, Kazuki Tokumasu, Yuki Otsuka, Yasuhiro Nakano, Yoshihisa Hanayama, Masanori Furukawa, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine 11 ( 5 ) 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Various symptoms persist even after the acute symptoms in about one third of patients with COVID-19. In February 2021, we established an outpatient clinic in a university hospital for patients with long COVID and started medical treatment for sequelae that persisted one month or more after infection. METHODS: To determine the key factors that affect the onset and clinical course of sequelae, a retrospective analysis was performed at Okayama University Hospital (Japan) between February and July 2021. We focused on changes in the numbers of symptoms and the background of the patients during a three-month period from the first outpatient visit. We also examined the relationship with SARS-CoV-2 antibody titers. RESULTS: Information was obtained from medical records for 65 patients. The symptoms of sequelae were diverse, with more than 20 types. The most frequent symptoms were general malaise, dysosmia, dysgeusia, sleeplessness, and headache. These symptoms improved in about 60% of the patients after 3 months. Patients who required hospitalization and had a poor condition in the acute phase and patients who received oxygen/dexamethasone therapy had higher antibody titers at the time of consultation. Patients with antibody titers ≥200 U/mL showed significantly fewer improvements in long COVID symptoms in 1 month, but they showed improvements at 3 months after the first visit. CONCLUSION: Long COVID symptoms were improved at 3 months after the initial visit in more than half of the patients. Serum antibody titers were higher in patients who experienced a severe acute phase, but the serum antibody titers did not seem to be directly related to the long-term persistence of long COVID symptoms.

DOI： 10.3390/jcm11051309

Foramen of Winslow Hernia Ameliorating Conservatively.

Hiroyuki Honda, Hiroyuki Sakae, Hideharu Hagiya, Fumio Otsuka

Internal medicine (Tokyo, Japan) 61 ( 18 ) 2817 - 2818 2022年2月

Adult-onset Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion Induced by MRSA Endocarditis 国際誌

Hideharu Hagiya, Fumio Otsuka

European Journal of Case Reports in Internal Medicine 9 ( 2 ) 003185 - 003185 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SMC Media

Background: Mild encephalitis/encephalopathy and a reversible splenial lesion (MERS) is a clinicoradiological syndrome with an unknown pathogenic mechanism, which usually involves children. Thus, adult-onset MERS is quite rare. Case presentation: A 71-year-old man, undergoing haemodialysis due to diabetes-induced chronic kidney disease, manifested a persistent fever and disorientation. Blood culture detected methicillin-resistant Staphylococcus aureus (MRSA), while echocardiography revealed vegetation in the aortic and mitral valves. Magnetic resonance imaging of the head revealed a fluid-attenuated inversion recovery-high, diffusion-weighted image-high lesion in the splenium of the corpus callosum, with a number of emboli. Accordingly, the patient was diagnosed with MERS induced by MRSA endocarditis. Discussion: Neurological impairment by MERS can be reversible. However, the differential diagnosis of the disease includes ischaemic lesions, multiple sclerosis, malignant lymphoma, acute disseminated encephalomyelitis, and posterior reversible encephalopathy. Clinicians should consider these diseases when MERS is suspected.

DOI： 10.12890/2022_003185

Clinical Utility of 4C Mortality Scores among Japanese COVID-19 Patients: A Multicenter Study. 国際誌

Kazuki Ocho, Hideharu Hagiya, Kou Hasegawa, Kouji Fujita, Fumio Otsuka

Journal of clinical medicine 11 ( 3 ) 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: We analyzed data from COVID-19 patients in Japan to assess the utility of the 4C mortality score as compared with conventional scorings. METHODS: In this multicenter study, COVID-19 patients hospitalized between March 2020 and June 2021, over 16 years old, were recruited. The superiority for correctly predicting mortality and severity by applying the receiver operating characteristic (ROC) curve was compared. A Cox regression model was used to compare the length of hospitalization for each risk group of 4C mortality score. RESULTS: Among 206 patients, 21 patients died. The area under the curve (AUC) (95% confidential interval (CI)) of the ROC curve for mortality and severity, respectively, of 4C mortality scores (0.84 (95% CI 0.76-0.92) and 0.85 (95% CI 0.80-0.91)) were higher than those of qSOFA (0.66 (95% CI 0.53-0.78) and 0.67 (95% CI 0.59-0.75)), SOFA (0.70 (95% CI 0.55-0.84) and 0.81 (95% CI 0.74-0.89)), A-DROP (0.78 (95% CI 0.69-0.88) and 0.81 (95% CI 0.74-0.88)), and CURB-65 (0.82 (95% CI 0.74-0.90) and 0.82 (95% CI 0.76-0.88)). For length of hospitalization among survivors, the intermediate- and high- or very high-risk groups had significantly lower hazard ratios, i.e., 0.48 (95% CI 0.30-0.76)) and 0.23 (95% CI 0.13-0.43) for discharge. CONCLUSIONS: The 4C mortality score is better for estimating mortality and severity in COVID-19 Japanese patients than other scoring systems.

DOI： 10.3390/jcm11030821

Threat of Staphylococcus aureus Pneumonia in Severe COVID-19 Patients. 国際誌

Shuichi Tanaka, Koichiro Yamamoto, Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka

Cureus 14 ( 2 ) e22486 2022年2月

記述言語：英語

Coronavirus disease 2019 (COVID-19) has been spreading worldwide with unprecedented rapidity. Staphylococcus aureus is reported to frequently cause bacterial complications in patients with COVID-19. We herein present two additional cases of S. aureus pneumonia involving such patients. The first case was an obese 48-year-old man without any particular underlying diseases. The second case was another patient, a 72-year-old man, with hypertension, dyslipidemia, and steatohepatitis. Both patients developed methicillin-susceptible S. aureus pneumonia in the clinical course of COVID-19, to which antibiotic therapy with cefazolin was effectively administered. Through these cases, we emphasize that S. aureus secondary infections should be well cared with a high degree of caution in a case of critically ill COVID-19 patients.

DOI： 10.7759/cureus.22486

Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice.

Masao Takami, Koichiro Yamamoto, Yoshihisa Hanayama, Yasuhiro Nakano, Kou Hasegawa, Mikako Obika, Hideharu Hagiya, Masanori Furukawa, Fumio Otsuka

Acta medica Okayama 76 ( 1 ) 7 - 15 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH.

DOI： 10.18926/AMO/63203

Calcified spleen associated with Pneumocystis jirovecii infection

ラット顆粒膜細胞による卵巣ステロイド合成におけるBMP-15が関与したグルココルチコイド作用(Involvement of BMP-15 in glucocorticoid actions on ovarian steroidogenesis by rat granulosa cells)

Kashino Chiaki, Hasegawa Toru, Kamada Yasuhiko, Masuyama Hisashi, Otsuka Fumio

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 187 2022年2月

右肩・上腕痛及び右手先の痺れから見つかった食道癌の一例

吉田純, 田中秀一, 山本紘一郎, 高橋美砂, 本多寛之, 長谷川功, 大塚文男

日本病院総合診療医学会雑誌 18 ( 臨増1 ) O - 002 2022年2月

COVID-19後遺症状の診療において大学病院総合内科が果たせる役割

大塚勇輝, 徳増一樹, 中野靖浩, 本多寛之, 萩谷英大, 砂田匠彦, 櫻田泰江, 山本幸近, 大村大輔, 松田祐依, 長谷川功, 小比賀美香子, 植田圭吾, 片岡仁美, 大塚文男

日本病院総合診療医学会雑誌 18 ( 臨増1 ) N - 010 2022年2月

右肩・上腕痛及び右手先の痺れから見つかった食道癌の一例

吉田純, 田中秀一, 山本紘一郎, 高橋美砂, 本多寛之, 長谷川功, 大塚文男

日本病院総合診療医学会雑誌 18 ( 臨増1 ) O - 002 2022年2月

COVID-19後遺症状の診療において大学病院総合内科が果たせる役割

日本病院総合診療医学会雑誌 18 ( 臨増1 ) N - 010 2022年2月

Bull's Head Sign.

Koichiro Yamamoto, Hiroyuki Honda, Hideharu Hagiya, Fumio Otsuka

JMA journal 5 ( 1 ) 130 - 131 2022年1月

K Yamamoto, H Honda, H Hagiya, F Otsuka

QJM: An International Journal of Medicine 114 ( 12 ) 895 - 895 2022年1月

Recovery From Alopecia After COVID-19. 国際誌

Yuki Otsuka, Yasuhiro Nakano, Hideharu Hagiya, Kazuki Tokumasu, Fumio Otsuka

Cureus 14 ( 1 ) e21160 2022年1月

記述言語：英語

Herein, we report a remarkable case of post-coronavirus disease 2019 (COVID-19) diffuse alopecia that gradually improved and recovered, and the hair volume returned approximately to the pre-infection level, seven months after the patient's first diagnosis of COVID-19. Approximately 20% of patients with COVID-19 develop alopecia a few months after the acute infection phase. Telogen effluvium is the major type of COVID-19 sequela secondary to physical or psychological distress. It is reversible and is expected to improve without any treatment, and it can be addressed by explaining to the patients their conditions, sharing medical information, and eliminating psychophysical stress by managing systemic complications.

DOI： 10.7759/cureus.21160

Enriched CD45RA⁻CD62L⁺ central memory T and decreased CD3⁺CD56⁺ natural killer T lymphocyte subsets in the rectum of ulcerative colitis patients

Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

International Journal of Immunopathology and Pharmacology 36 205873842110519 - 205873842110519 2022年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：SAGE Publications

Objectives

To investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis.

Methods

We performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients ( n = 13) and control patients ( n = 5).

Results

CD62L⁺/CD3⁺CD4⁺ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L⁺/CD3⁺CD4⁻ cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA⁻CD62L⁺/CD3⁺CD4⁺, that is, central memory T cell fraction in CD4⁺ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56⁺/CD3⁺ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56⁺/CD3⁺ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%).

Conclusion

We demonstrated that CD62L⁺ T lymphocytes, particularly the CD45RA⁻CD62L⁺ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56⁺/CD3⁺ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.

DOI： 10.1177/20587384211051982

Enriched CD45RA⁻CD62L⁺ central memory T and decreased CD3⁺CD56⁺ natural killer T lymphocyte subsets in the rectum of ulcerative colitis patients 国際誌

その他リンク： http://journals.sagepub.com/doi/full-xml/10.1177/20587384211051982

Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

International Journal of Immunopathology and Pharmacology 36 205873842110519 - 205873842110519 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SAGE Publications

DOI： 10.1177/20587384211051982

その他リンク： http://journals.sagepub.com/doi/full-xml/10.1177/20587384211051982

Interest in Infectious Diseases specialty among Japanese medical students amidst the COVID-19 pandemic: A web-based, cross-sectional study. 国際誌

Hideharu Hagiya, Yuki Otsuka, Kazuki Tokumasu, Hiroyuki Honda, Yoshito Nishimura, Mikako Obika, Fumio Otsuka

PloS one 17 ( 4 ) e0267587 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The emergence of the novel coronavirus disease of 2019 (COVID-19) has led to huge disruptions in the medical field and society. The significance of training and education for experts has been increasingly acknowledged in Japan, where the number of infectious disease (ID) specialists is reportedly insufficient. In this paper, we report the results of a web-based survey that was conducted to reveal the ways in which the COVID-19 pandemic has influenced medical students' awareness of ID specialists and future career choices. METHOD: This cross-sectional descriptive study was conducted in March 2021 and targeted 717 medical students belonging to Medical School of Okayama University, Japan. The questionnaire consisted of four questions meant to assess students' knowledge and future intentions of becoming ID specialists. RESULTS: We obtained 328 eligible questionnaires (response rate: 45.7%). Of 227 (69.2%) students who were aware of ID specialists, 99 (43.6%) answered that they came to know about them only after the pandemic, 12 (3.7%) answered that their interest in being an ID specialist arose during the pandemic, while 36 (11.0%) responded that they would rather not become ID specialists. At the time of the survey, 5 students (1.5%) were aiming to become ID specialists. CONCLUSION: We observed a very low rate of interest to be an ID specialist among medical students. The experience of the pandemic does not seem to have influenced Japanese medical students to choose ID as a specialty for their careers. Continuous efforts to increase the number of ID specialists are necessary in Japan as a countermeasure against the coming pandemic.

DOI： 10.1371/journal.pone.0267587

Fear of an unprecedented, invisible enemy: Difficulties experienced in establishing criteria for the release of COVID-19 patients from isolation in a Japanese University Hospital. 国際誌

Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka

PloS one 17 ( 4 ) e0266853 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, and the United States and European authorities established criteria for the release of COVID-19 patients from isolation in October 2020. However, a huge discrepancy exists between the hospital-discharge protocol for COVID-19 patients and the release of patients from in-hospital isolation. Our initially proposed criteria for in-hospital release from isolation was not adhered to by healthcare workers (HCWs) due to prevailing concerns regarding disease infectivity. Herein, we report difficulties encountered in attempting to establish a common understanding of the management of emerging infections. METHODS: We performed a Google Form-based questionnaire survey targeting HCWs from Okayama University Hospital, Japan, via e-mail on January 21-28, 2021. The anonymous investigation required respondents to provide information regarding their background as well as perceptions regarding the requirement, level of understanding, and readiness for developing release criteria. RESULTS: We obtained 150 eligible responses, including 57 (38.0%) from medical doctors and 53 (35.3%) from nurses. Most HCWs managing COVID-19 patients advocated for the implementation of the criteria, whereas those not working in that capacity did not (p<0.001). Over half of the HCWs indicated discomfort at seeing COVID-19 patients transitioning to general management even after meeting the criteria. CONCLUSIONS: It was challenging to establish a common understanding regarding the ideal criteria for in-hospital release of COVID-19 patients from isolation in our hospital. The dissemination of our experiences and multifaceted discussions with HCWs would be of great value as a countermeasure against the emergent pandemic.

DOI： 10.1371/journal.pone.0266853

Association between fever and antibody titer trends after a third dose of the mRNA-1273 vaccine

Naomi Matsumoto, Tomoka Kadowaki, Rumi Matsuo, Ayako Sasaki, Chikara Miyaji, Chigusa Higuchi, Masanori Nakayama, Yasue Sakurada, Hideharu Hagiya, Soshi Takao, Fumio Otsuka, Takashi Yorifuji

Journal of Epidemiology 32 ( 12 ) 567 - 569 2022年

Possibility of endocrine dysfunction in post coronavirus disease 2019 (COVID-19) condition

Yuki Otsuka, Fumio Otsuka

Endocrine Journal 69 ( 11 ) 1357 - 1357 2022年

Quality, as well as Quantity, of Universal Masking Matters amid the COVID-19 pandemic: A Comparison of Appropriate Masking between Healthcare Workers and Non-medical Personnel

Hideharu Hagiya, Hitoshi Osada, Hana Iguchi, Kotaro Takahashi, Kazuki Tokumasu, Mikako Obika, Fumio Otsuka

2022年

Comment on: Short versus prolonged courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection: a retrospective study. 国際誌

Hideharu Hagiya, Fumio Otsuka

The Journal of antimicrobial chemotherapy 77 ( 3 ) 857 - 858 2021年12月

Adult Hypogonadism Due to Testicular Adrenal Rest Tumors.

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 60 ( 23 ) 3839 - 3840 2021年12月

GH補充療法により脂肪肝の著明な改善を認めたAGHDの1例

高瀬了輔, 中野靖浩, 山本紘一郎, 越智可奈子, 本多寛之, 長谷川功, 三好智子, 小川弘子, 大塚文男

日本内分泌学会雑誌 97 ( 4 ) 951 - 951 2021年12月

総合診療における甲状腺機能低下状態の潜在とその特徴

高見優男, 山本紘一郎, 花山宜久, 中野靖浩, 長谷川功, 小比賀美香子, 萩谷英大, 大塚文男

日本内分泌学会雑誌 97 ( 4 ) 961 - 961 2021年12月

乳汁漏出の精査より判明したBigプロラクチンと性同一性障害の合併例

桜田泰江, 越智可奈子, 山本紘一郎, 古川雅規, 大塚文男

日本内分泌学会雑誌 97 ( 4 ) 953 - 953 2021年12月

肺癌治療中の発熱を契機に発見されたペムブロリズマブによるirAEの1例

平仲凪, 山本紘一郎, 田中秀一, 孫麗那, 高橋美砂, 本多寛之, 長谷川功, 大塚文男

日本内分泌学会雑誌 97 ( 4 ) 951 - 951 2021年12月

MEN1疑いの家族歴と上縦隔に進展する副甲状腺癌を認めた1例

大塚勇輝, 長谷川功, 原田洸, 西村義人, 岡浩介, 小野早和子, 枝園忠彦, 平沢晃, 大塚文男

日本内分泌学会雑誌 97 ( 4 ) 946 - 946 2021年12月

Roles of NR5A1 and NR5A2 in the regulation of steroidogenesis by Clock gene and bone morphogenetic proteins by human granulosa cells.

Atsuhito Suyama, Nahoko Iwata, Yoshiaki Soejima, Yasuhiro Nakano, Koichiro Yamamoto, Takahiro Nada, Fumio Otsuka

Endocrine journal 68 ( 11 ) 1283 - 1291 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN ENDOCRINE SOC

The functional role of the transcription factors NR5A1 and NR5A2 and their interaction with Clock gene and bone morphogenetic proteins (BMPs) were investigated in human granulosa KGN cells. Treatment with BMP-15 and GDF-9 suppressed forskolin (FSK)-induced steroidogenesis as shown by the mRNA expression levels of StAR and P450scc but not the mRNA expression level of P450arom. Of interest, treatment with BMP-15 and GDF-9 also suppressed FSK-induced NR5A2 mRNA expression. Treatment with BMP-15 suppressed NR5A2 mRNA and protein expression but increased Clock mRNA and protein expression levels by granulosa cells. The mRNA expression levels of NR5A1, but not those of NR5A2, were positively correlated with the levels of Clock mRNA, while the mRNA levels of Id-1, the target gene of BMP signaling, were positively correlated with those of NR5A1 but not with those of NR5A2. It was also demonstrated that the mRNA expression levels of NR5A1 were positively correlated with those of P450arom and 3βHSD, whereas the mRNA expression level of NR5A2 was correlated with those of StAR and P450scc. Furthermore, inhibition of Clock gene expression by siRNA attenuated the expression of NR5A1, and the mRNA levels of Clock gene were significantly correlated with those of NR5A1. Collectively, the results suggested a novel mechanism by which Clock gene expression induced by BMP-15 is functionally linked to the expression of NR5A1, whereas NR5A2 expression is suppressed by BMP-15 in granulosa cells. The interaction between Clock NR5A1/NR5A2 and BMP-15 is likely to be involved in the fine-tuning of steroidogenesis by ovarian granulosa cells.

DOI： 10.1507/endocrj.EJ21-0223

Burnout of Healthcare Workers Amid the COVID-19 Pandemic: A Follow-Up Study. 国際誌

Yoshito Nishimura, Tomoko Miyoshi, Asuka Sato, Kou Hasegawa, Hideharu Hagiya, Yoshinori Kosaki, Fumio Otsuka

International journal of environmental research and public health 18 ( 21 ) 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to the modern healthcare system and led to increased burnout among healthcare workers (HCWs). We previously reported that HCWs who engaged in COVID-19 patient care had a significantly higher prevalence of burnout (50.0%) than those who did not in November 2020 (period 1). We performed follow-up surveys in HCWs in a Japanese national university hospital, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks, and the Maslach Burnout Inventory in February 2021 (period 2) and May 2021 (period 3). Periods 1 and 3 were amid the surges of COVID-19 cases, and period 2 was a post-surge period with a comparatively small number of COVID-19 patients requiring hospitalization. Response rates to the surveys were 33/130 (25.4%) in period 1, 36/130 (27.7%) in period 2, and 56/162 (34.6%) in period 3, respectively. While no consistent tendency in the prevalence of burnout based on variables was observed throughout the periods, the prevalence of burnout tends to be higher in periods 1 and 3 in those who engaged in COVID-19 patient care in the last 2 weeks (50.0%, 30.8%, 43.1% in period 1, 2, and 3, respectively). Given the prolonged pandemic causing stigmatization and hatred against HCWs leading to increased prevalence of burnout, high-level interventions and supports are warranted.

DOI： 10.3390/ijerph182111581

Clinical utility of urinary levels of catecholamines and their fraction ratios related to heart rate and thyroid function.

Naruhiko Sunada, Yoshihisa Hanayama, Koichiro Yamamoto, Yasuhiro Nakano, Takahiro Nada, Hiroyuki Honda, Kou Hasegawa, Hideharu Hagiya, Fumio Otsuka

Endocrine journal 69 ( 4 ) 417 - 425 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

DOI： 10.1507/endocrj.EJ21-0488

新型コロナウイルス感染症対策における慰労金交付事業の影響およびその評価

萩谷英大, 三好智子, 西村義人, 徳増一樹, 本多寛之, 長谷川功, 小比賀美香子, 頼藤貴志, 大塚文男

日本病院総合診療医学会雑誌 17 ( 6 ) 608 - 616 2021年11月

記述言語：日本語出版者・発行元：(一社)日本病院総合診療医学会

新型コロナウイルス感染症対策の一環として,「新型コロナウイルス感染症対応従事者慰労金交付事業」が実施されたが,その影響・有効性に関するデータは乏しい。2021年4月26日〜5月31日に,岡山県・香川県・広島県の医療機関に勤務する職員を対象にウェブ・アンケートによる横断調査を実施した。1001名からの回答において,慰労金受給率は95.8%であり,59.5%は本事業に満足したと回答した。職種別満足度は,医師(60.8%),メディカルスタッフ(63.9%)に比べて看護職(46.3%)で低かった(p<0.001)。医療機関内職員のみならず,救急隊員,保健所職員,高齢者介護施設の職員も慰労金が支払われるべき業種として高率に理解を得た。慰労金交付事業は,医療従事者等の外的モチベーションとして概ね機能したと考えられるが,給付金額や対象者の選定に関しては検討の余地がある。(著者抄録)

Subcutaneous edema as rare complication of abdominal paracentesis. 国際誌

Yuki Otsuka, Hirokazu Nagaoka, Yasuhiro Nakano, Hiroyuki Sakae, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 11 ) e05116 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Although ascites leakage to the skin is the most frequent complication after abdominal paracentesis, leakage to the subcutaneous space has not been reported. Here, we report a subcutaneous effusion after paracentesis suggesting ascites leakage. We should be aware of this rare complication due to the potential risk of dissemination.

DOI： 10.1002/ccr3.5116

【COVID-19-その診断と治療】倦怠感

大塚勇輝, 徳増一樹, 本多寛之, 萩谷英大, 大塚文男

カレントテラピー 39 ( 11 ) 1034 - 1039 2021年11月

記述言語：日本語出版者・発行元：(株)ライフメディコム

新型コロナウイルス感染症(COVID-19)が最初に報告されてからおよそ1年半が経過したが、いまだ収束の兆しの見えない世界的流行のなかで「Long-COVID」ないし「post-acute sequelae of COVID-19(PASC)」と定義され、一般には「コロナ後遺症」として知られる、急性期以降に残存する症状に悩まされる患者が多く存在している。そのなかでも「倦怠感」は、最も多い症状として報告され、COVID-19罹患後に4割程度の患者が自覚すると言われている。倦怠感は視認できず検査での客観的評価も難しい症状である一方で、さまざまな要因が複雑に絡みあって生じており病態メカニズムも未解明なところが多く、診療に難渋する。われわれは2021年2月にLong-COVID/PASCを専門的に診療する「コロナ・アフターケア(COVID-19 aftercare:CAC)外来」を大学病院内にいち早く設立し、倦怠感などの症状に悩む患者の診療と研究・教育に取り組んできた。本稿ではそうしたわれわれの診療経験も踏まえ、診断や治療を行ううえでの対面診療の必要性や総合診療的アプローチの重要性についても触れながら、Long-COVID/PASCにおける倦怠感について概説する。(著者抄録)

Impact of the world hand hygiene and global handwashing days on public awareness between 2016 and 2020: Google trends analysis. 国際誌

Yoshito Nishimura, Hideharu Hagiya, Koichi Keitoku, Toshihiro Koyama, Fumio Otsuka

American journal of infection control 50 ( 2 ) 141 - 147 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Scientific evidence suggest that hand hygiene as one of the most effective measures to control infection. To promote good hand hygiene practices, the World Health Organization introduced May 5 as World Hand Hygiene Day (WHHD), and international stakeholders established Global Handwashing Day (GHD) on October 15. However, its contributions to raising public awareness of hand hygiene is unclear. METHODS: This study evaluates the impact of the WHHD and GHD on the public awareness of hand hygiene in Japan, the United Kingdom, the United States, and worldwide from 2016 to 2020, using the relative search volume of "Hand hygiene" in Google Trends as a surrogate. To identify a statistically significant timepoint of a trend change, we performed Joinpoint regression analysis. RESULTS: Upticks of the relative search volumes as well as joinpoints were noted worldwide around the WHHD and GHD from 2016 to 2019, but no joinpoints were identified around the WHHD and GHD in 2020. No such changes were observed in Japan, the United Kingdom, and the United States during these periods. CONCLUSIONS: While the WHHD was originally established to raise awareness of hand hygiene in healthcare facilities, our result suggests that the WHHD and GHD may not have effectively disseminated the importance of hand hygiene to the general public at a country level. Additional policy measures to advocate hand hygiene to the public are necessary to communicate its benefits.

DOI： 10.1016/j.ajic.2021.08.033

Temporal artery thickening in giant cell arteritis. 国際誌

Hiromi Ihoriya, Yasuhiro Nakano, Fumio Otsuka

BMJ case reports 14 ( 10 ) 2021年10月

Radiologic features of Erdheim-Chester disease. 国際誌

Koichiro Yamamoto, Yasuhiro Nakano, Kou Hasegawa, Fumio Otsuka

Rheumatology (Oxford, England) 61 ( 7 ) e209 2021年10月

Idiopathic combined adrenocorticotropin and growth hormone deficiency mimicking chronic fatigue syndrome. 国際誌

Kazuki Tokumasu, Kanako Ochi, Fumio Otsuka

BMJ case reports 14 ( 10 ) 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMJ PUBLISHING GROUP

A 42-year-old man who had suffered from severe fatigue for 5 years was diagnosed as having chronic fatigue syndrome (CFS) and fibromyalgia. Endocrinological workup using combined anterior pituitary function tests showed that the patient had adrenocorticotropin hormone (ACTH) deficiency, with a normal pituitary MRI. Treatment with a physiologic dose of oral hydrocortisone replacement physically ameliorated his general fatigue. A secondary workup using a growth hormone-releasing peptide-2 test revealed that he also had growth hormone (GH) deficiency, and GH replacement therapy was started. His muscle pain and depression were improved by the therapy. Here, we present a rare case of combined deficiency of ACTH and GH in a middle-aged man with severe general fatigue. This case report aims to raise awareness of combined deficiency of ACTH and GH as a differential diagnosis of CFS and its mimics.

DOI： 10.1136/bcr-2021-244861

Detection of in-frame mutation by IS30-family insertion sequence in the phospholipid phosphatidylglycerol synthase gene (pgsA2) of high-level daptomycin-resistant Corynebacterium striatum. 国際誌

Kazuyoshi Gotoh, I Putu Bayu Mayura, Yusaku Enomoto, Koji Iio, Osamu Matsushita, Fumio Otsuka, Hideharu Hagiya

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 41 ( 2 ) 331 - 333 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

The emergence of high-level daptomycin (DAP)-resistant (HLDR) Corynebacterium striatum has been reported as a result of loss-of-function point mutations or premature stop codon mutations in a responsible gene, pgsA2. We herein describe the novel detection of an HLDR C. striatum clinical isolate, in which IS30-insertion was corroborated to cause destruction of pgsA2 gene. We isolated an HLDR C. striatum from a critically ill patient with underlying mycosis fungoides who had been treated with DAP for 10 days. With a sequence investigation, IS30-insertion was discovered to split pgsA2 in the HLDR C. striatum strain, which may cause disrupted phospholipid phosphatidylglycerol (PG) production. Future studies should survey the prevalence of IS-mediated gene inactivation among HLDR C. striatum clinical isolates.

DOI： 10.1007/s10096-021-04369-1

Impact of the day of the week on the discontinuation of broad-spectrum antibiotic prescriptions; a multi-centered observational study. 国際誌

Hiroyuki Honda, Hideharu Hagiya, Tsukasa Higashionna, Yuto Haruki, Mai Haruki, Shiho Kajita, Kengo Mukuda, Yuji Yokoyama, Yasuhiro Nakano, Hiroko Ogawa, Yasuyo Morimoto, Yoshihisa Hanayama, Setsuko Kanda, Hitomi Kataoka, Hitomi Muguruma, Fumio Otsuka

Scientific reports 11 ( 1 ) 20784 - 20784 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PORTFOLIO

To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future.

DOI： 10.1038/s41598-021-00206-9

Biphasic Roles of Clock Genes and Bone Morphogenetic Proteins in Gonadotropin Expression by Mouse Gonadotrope Cells. 国際誌

Yoshiaki Soejima, Nahoko Iwata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Takahiro Nada, Fumio Otsuka

International journal of molecular sciences 22 ( 20 ) 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI

Roles of Clock genes and the bone morphogenetic protein (BMP) system in the regulation of gonadotropin secretion by gonadotropin-releasing hormone (GnRH) were investigated using mouse gonadotropin LβT2 cells. It was found that luteinizing hormone (LH)β mRNA expression level in LβT2 cells changed gradually over time, with LHβ expression being suppressed in the early phase up to 12 h and then elevated in the late phase 24 h after GnRH stimulation. In addition, the mRNA expression levels of Clock genes, including Bmal1, Clock, Per2, and Cry1, also showed temporal changes mimicking the pattern of LHβ expression in the presence and absence of GnRH. Notably, the expression levels of Bmal1 and Clock showed strong positive correlations with LHβ mRNA expression levels. Moreover, a functional link of the ERK signaling of mitogen-activated protein kinases (MAPKs) in the suppression of LHβ mRNA expression, as well as Bmal1 and Clock mRNA expression by GnRH at the early phase, was revealed. Inhibition of Bmal1 and Clock expression using siRNA was involved in the reduction in LHβ mRNA levels in the late phase 24 h after GnRH stimulation. Furthermore, in the presence of BMP-6 and -7, late-phase Bmal1 and LHβ mRNA expression after GnRH stimulation was significantly attenuated. Collectively, the results indicated that LH expression in gonadotrope cells exhibits Bmal1/Clock-dependent fluctuations under the influence of GnRH and that the fluctuations are regulated by ERK and BMPs in the early and late stages, respectively, in a phase-dependent manner after GnRH stimulation.

DOI： 10.3390/ijms222011186

Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease. 国際誌

Yoshito Nishimura, David C Fajgenbaum, Sheila K Pierson, Noriko Iwaki, Asami Nishikori, Mitsuhiro Kawano, Naoya Nakamura, Koji Izutsu, Kengo Takeuchi, Midori Filiz Nishimura, Yoshinobu Maeda, Fumio Otsuka, Kazuyuki Yoshizaki, Eric Oksenhendler, Frits van Rhee, Yasuharu Sato

American journal of hematology 96 ( 10 ) 1241 - 1252 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword "TAFRO" to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO.

DOI： 10.1002/ajh.26292

Clinical Characteristics of Japanese Patients Who Visited a COVID-19 Aftercare Clinic for Post-Acute Sequelae of COVID-19/Long COVID. 国際誌

Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Naruhiko Sunada, Daisuke Omura, Kou Hasegawa, Hideharu Hagiya, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Cureus 13 ( 10 ) e18568 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CUREUS INC

Introduction The long-term clinical course, prognosis, and optimal management of symptoms and conditions after the acute phase of coronavirus disease 2019 (COVID-19) remain to be elucidated. The purpose of this study was to clarify the characteristics of patients referred to a COVID-19 aftercare (CAC) clinic established at a tertiary academic hospital in Japan. Methods This study was a descriptive case series study. All patients who visited the CAC clinic between February 15 and September 17 in 2021 were included. Patients' background, chief complaints, and clinical courses after the onset of COVID-19 were described. Results A total of 87 Japanese patients (median age, 40.0 years; interquartile range [IQR], 26.5-53.0 years; 52.9% women) were referred to the CAC clinic. The median interval between the onset of COVID-19 and the visit to the clinic was 79.0 (IQR, 52.5-112.0) days. Referral sources were hospitals (36 patients), clinics (47 patients), a local healthcare center (3 patients), and other (1 patient). The most common chief complaint was general fatigue (50.4%) followed by dysosmia (28.7%), dysgeusia (26.4%), hair loss (18.4%), headache (17.2%), dyspnea (16.1%), and dyssomnia (13.1%). Respiratory symptoms were common in the early stages of the disease but were less common as the chief complaints when visiting the clinic. On the other hand, neurological, psychiatric, and extremity symptoms were predominant one month after the onset of COVID-19. Conclusions Regardless of the severity in the acute phase, patients visiting our CAC clinic suffered from a variety of symptoms. General physicians skilled in using a comprehensive approach would be optimal to see patients with such complex symptoms.

DOI： 10.7759/cureus.18568

Celiac artery dissection in polycystic kidney disease. 国際誌

Koichiro Yamamoto, Kou Hasegawa, Kosuke Oka, Fumio Otsuka

Clinical case reports 9 ( 10 ) e04922 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Autosomal-dominant polycystic kidney disease (ADPKD) is rarely complicated by celiac artery dissection. Dissection of the aorta and its major branches should be carefully differentiated in ADPKD patients with acute-onset abdominal pain.

DOI： 10.1002/ccr3.4922

In vitro effectiveness of biapenem against IMP-producing Enterobacteriaceae. 国際誌

Kazuyoshi Gotoh, Makoto Miyoshi, I Putu Bayu Mayura, Koji Iio, Osamu Matsushita, Fumio Otsuka, Hideharu Hagiya

Journal of medical microbiology 70 ( 10 ) 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MICROBIOLOGY SOC

The options available for treating infections with carbapenemase-producing Enterobacteriaceae (CPE) are limited; with the increasing threat of these infections, new treatments are urgently needed. Biapenem (BIPM) is a carbapenem, and limited data confirming its in vitro killing effect against CPE are available. In this study, we examined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of BIPM for 14 IMP-1-producing Enterobacteriaceae strains isolated from the Okayama region in Japan. The MICs against almost all the isolates were lower than 0.5 µg ml-1, indicating susceptibility to BIPM, while approximately half of the isolates were confirmed to be bacteriostatic to BIPM. However, initial killing to a 99.9 % reduction was observed in seven out of eight strains in a time-kill assay. Despite the small data set, we concluded that the in vitro efficacy of BIPM suggests that the drug could be a new therapeutic option against infection with IMP-producing CPE.

DOI： 10.1099/jmm.0.001430

Impact of the World Antimicrobial Awareness Week on public interest between 2015 and 2020: A Google Trends analysis. 国際誌

Koichi Keitoku, Yoshito Nishimura, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 111 12 - 20 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

OBJECTIVES: To evaluate the impact of the World Antimicrobial Awareness Week (WAAW) on public awareness of antimicrobial resistance using Google Trends analysis. METHODS: The impact of WAAW on public awareness of 'antimicrobial resistance' (AMR), 'antibacterial', and 'antibiotics' in Japan, the UK, the United States, and worldwide from 2015 to 2020 was analyzed, using the relative search volume (RSV) of Google Trends as a surrogate. A joinpoint regression analysis was performed to identify a statistically significant time point of a change in trend. RESULTS: No joinpoints around WAAW were identified in Japan, the United Kingdom, or the United States from 2015 to 2020 with RSVs of 'AMR', whereas increasing RSVs were noted worldwide in 2017 and 2020. Further, there were decreasing RSVs of 'antibiotics' in the first half of 2020, which could be due to the COVID-19 pandemic. The study results suggest that WAAW did little to improve public awareness of AMR in the selected countries despite its contribution worldwide. CONCLUSIONS: This study implies that we need to develop a more effective method to improve public awareness to fight against AMR.

DOI： 10.1016/j.ijid.2021.08.018

Intravascular lymphoma presenting as spinal cord infarction 国際誌

Yukichika Yamamoto, Yoshito Nishimura, Misa Okumura, Yuki Otsuka, Kosuke Oka, Kazuhiro Ikeuchi, Hisakazu Nishimori, Kohei Taniguchi, Fumio Otsuka

Postgrad. Med. J 97 ( 1152 ) 672 - 673 2021年10月

COVID-19外国人入院診療の実際

大塚勇輝, 萩谷英大, 中野靖浩, 大村大輔, 長谷川功, 大塚文男

日本医師会雑誌 150 ( 7 ) 1237 - 1241 2021年10月

記述言語：日本語出版者・発行元：(公社)日本医師会

国際化を背景に、在日外国人も新型コロナウイルス感染症(COVID-19)に罹患しているが、本邦でその診療上の課題に関する文献はない。2020年2月からの1年間に岡山大学病院総合内科・総合診療科に入院した、外国人COVID-19患者全5人を対象として、患者背景や言語状況、入院中のトラブルや解決策について診療録から抽出した。全員が日本語の書字・読字が全く不能であり、うち1人は日常会話も困難で電話医療通訳サービスを要したが、担当医や看護師に加えて、国際診療支援センターや臨床栄養部、精神科などと連携することで隔離解除まで入院継続が可能であった。COVID-19では本人の希望に沿わない入院や予定外入院のため、通常の外国人診療に比して負担・課題が大きい。特に言語面での制約は、隔離管理下での意思疎通や同意書の取得などの面で障壁となることが明らかとなった。院内組織の連携と、病院を超えた情報共有による病軟な対応が重要である。(著者抄録)

Impact of the World Inflammatory Bowel Disease Day and Crohn’s and Colitis Awareness Week on Population Interest Between 2016 and 2020: Google Trends Analysis

Krixie Silangcruz, Author Orcid Image, Yoshito Nishimura, Author Orcid Image, Torrey Czech, Author Orcid Image, Nobuhiko Kimura, Author Orcid Image, Hideharu Hagiya, Author Orcid Image, Toshihiro Koyama, Author Orcid Image, Fumio Otsuka, Author Orcid Image

2021年10月

Triad signs shown by bone scintigraphy in FGF23-related osteomalacia. 国際誌

Koichiro Yamamoto, Hiroyuki Honda, Itsuro Ota, Fumio Otsuka

QJM : monthly journal of the Association of Physicians 2021年9月

Sternoclavicular Joint Hypertrophy Involved in Polymyalgia Rheumatica.

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 60 ( 18 ) 3057 - 3057 2021年9月

Ivermectin for Coronavirus Disease 2019: Yet to Be Well Evaluated Before Clinical Use. 国際誌

Hideharu Hagiya, Fumio Otsuka

Clinical therapeutics 43 ( 9 ) 1622 - 1623 2021年9月

Gender-Dependent Characteristics of Serum 1,25-Dihydroxyvitamin D/25-Hydroxyvitamin D Ratio for the Assessment of Bone Metabolism. 国際誌

Manami Fujita-Yamashita, Koichiro Yamamoto, Hiroyuki Honda, Yoshihisa Hanayama, Kazuki Tokumasu, Yasuhiro Nakano, Kou Hasegawa, Hideharu Hagiya, Mikako Obika, Hiroko Ogawa, Fumio Otsuka

Cureus 13 ( 9 ) e18070 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CUREUS INC

Objectives Vitamin D deficiency, which is common worldwide, increases the risks of falls and fractures and can lead to increased morbidity and mortality. However, the clinical utility and relevance of vitamin D activation remain unknown. The aim of the present study was to clarify the clinical usefulness of serum 1,25-dihydroxyvitamin D (1,25D)/25-hydroxyvitamin D (25D) ratio for assessment of the extent of bone metabolism. Methods We retrospectively screened data for 87 patients whose serum 1,25D and 25D levels were measured. Eight patients who were taking vitamin D preparations were excluded, and data for 79 patients (33 males and 46 females) were analyzed. Since menopausal status can be associated with serum vitamin D level, we divided the patients by gender and divided the female patients into two groups at the age of 50 years. Results The median serum 1,25D/25D ratio was significantly lower in males than in females, with the most considerable difference in all males [4.1 (interquartile range: 2.3-5.8) × 10-3] versus elderly females (aged ≧50 years) [7.9 (3.3-10.1) × 10-3). Main disorders were endocrine (30.6%), inflammatory (18.5%), and bone-related (16.7%) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual-energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between the 1,25D/25D ratio and serum levels of inorganic phosphate (iP), parathyroid hormone, and alkaline phosphatase (ALP). The 1,25D/25D ratio had gender-specific characteristics: the ratio was significantly correlated with age in males (R=-0.49), while it was significantly correlated with BMI in females (R=0.34). Conclusions The results of this study suggested that vitamin D activity is negatively correlated with bone mineral density, being reduced in aged males but enhanced in obese females.

DOI： 10.7759/cureus.18070

Candidemia in COVID-19 treated with corticosteroids and tocilizumab. 国際誌

Koichiro Yamamoto, Kaoru Nakamura, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 9 ( 9 ) e04858 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

COVID-19 patients treated with anti-inflammatory drugs are rarely complicated by candidemia. Since immunosuppressive therapy can blunt inflammatory reactions, clinicians should actively survey latent candidemia during severe COVID-19 treatment.

DOI： 10.1002/ccr3.4858

下咽頭癌肺転移に対するペンブロリズマブ投与中に発症したACTH単独欠損症の1例

山本紘一郎, 徳増一樹, 孫麗那, 岡浩介, 長谷川功, 大塚文男

ACTH RELATED PEPTIDES 32 18 - 20 2021年9月

記述言語：日本語出版者・発行元：間脳・下垂体・副腎系研究会

70歳代、男性。下咽頭癌肺転移に対するペンブロリズマブの投与中に発熱や食思不振、嘔吐が持続し、精査目的で当科へ紹介となった。不明熱に対しての内分泌学的精査を施行し、ACTH単独欠損症(IAD)と診断され、ヒドロコルチゾン10mg/日の補充を開始したところ、症状・炎症反応の速やかな改善が得られた。病歴から本症例におけるIADの原因はペンブロリズマブによる免疫関連有害事象と考えられ、同薬剤の投与を中止することで、中止後も転移病変は縮小を維持している。

Total vascular resistance, augmentation index, and augmentation pressure increase in patients with peripheral artery disease. 国際誌

Rika Takemoto, Haruhito A Uchida, Hironobu Toda, Ken Okada, Fumio Otsuka, Hiroshi Ito, Jun Wada

Medicine 100 ( 32 ) e26931 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

ABSTRACT: Peripheral arterial disease (PAD) is one of major vascular diseases which frequently coexists with coronary arterial disease and cerebrovascular disease. The patients with PAD have a poor prognosis when it progresses. A new blood pressure testing device enables to simultaneously measure brachial blood pressure (BP), central BP, and several vascular parameters, with easy and non-invasive, in a short time. Here, we aimed to evaluate these arterial stiffness parameters in patients with PAD.In this study, 243 consecutive patients who were suspected of having PAD and referred to our hospital from September 2016 to June 2019, were registered. Several parameters, such as brachial BP, central BP, aortic pulse wave velocity (aPWV), total vascular resistance (TVR), augmentation index (AI) and augmentation pressure (AP), were determined by Mobil-O-Graph. Ankle-brachial pressure index (ABI) was used to define PAD (ABI ≤ 0.9 as PAD). The relationship between PAD and central BP, aPWV, TVR, AI, or AP were investigated.One hundred sixty-two patients (67%) were categorized as the PAD group and 81 patients (33%) as the non-PAD group. In the PAD group, the systolic brachial BP and central systolic BP were significantly higher than those in the non-PAD group (138 ± 24 mmHg vs 131 ± 19 mmHg, P < .05, 125 ± 22 mmHg vs 119 ± 18 mmHg, P < .05, respectively). TVR, AI, and AP were significantly higher in the PAD group (1785 ± 379 dyn s/cm5 vs 1661 ± 317 dyn s/cm5, P < .05, 26.2 ± 13.0% vs 22.2 ± 13.3%, P < .05, 13.5 ± 9.4 mmHg vs 10.7 ± 7.2 mmHg, P < .05, respectively). No significant differences in diastolic BP, central diastolic BP, and aPWV were found between the groups. Multivariate logistic regression analysis revealed that PAD was significantly associated with TVR, AI, and AP (P < .05, respectively).TVR/AP/AI were significantly higher in the PAD group than in the non-PAD group.

DOI： 10.1097/MD.0000000000026931

High-Dose Corticosteroids for a Pregnant Woman Critically Ill With Coronavirus Disease 2019. 国際誌

Koichiro Yamamoto, Hideharu Hagiya, Jota Maki, Shuji Okahara, Kou Hasegawa, Fumio Otsuka

Cureus 13 ( 8 ) e17398 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CUREUS INC

Pregnancy was reported to be a risk factor for coronavirus disease 2019 (COVID-19), with an increased risk for premature birth. Corticosteroids and remdesivir are used for patients with COVID-19; however, there is no established treatment for these patients. In particular, the effective management of pregnant, critically ill patients with COVID-19 remains unknown. We describe a 34-year-old, critically ill woman at 30 weeks of gestation with COVID-19, who was successfully treated with remdesivir and combined high-dose betamethasone (12 mg/day for two days) and methylprednisolone (125 mg/day for three days) followed by steroid tapering. During treatment, fetal biophysical profile scores on obstetric ultrasound were normal; her pregnancy course progressed well. Since high-dose corticosteroids improve fetal lung maturation and as well as cytokine storm due to COVID-19, this case provides an insight into the management of pregnant COVID-19 patients.

DOI： 10.7759/cureus.17398

No Association Observed Between the Number of Infectious Disease Experts and Prevalence of Antimicrobial-Resistant Pathogens in Japan. 国際誌

Hideharu Hagiya, Fumio Otsuka

Cureus 13 ( 8 ) e16918 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CUREUS INC

INTRODUCTION: The global spread of emerging infections has increased the demand for infectious disease (ID) experts. There is no established method to evaluate the sufficiency of professionals on a regional basis. We aimed to determine the correlation of the number of ID doctors and certified nurses in infection control (CNIC) with the prevalence of representative antimicrobial-resistant (AMR) pathogens across the 47 prefectures in Japan using publicly available databases. METHODS: We determined the number of ID doctors and CNIC registered in each prefecture based on the Japanese Association for Infectious Diseases and the Japanese Nursing Association websites and calculated their numbers per 100,000 population. Data on representative AMR pathogens were extracted from the Japan Nosocomial Infections Surveillance database. Spearman's correlation coefficient was used to measure statistical associations. RESULTS: There was no epidemiologically applicable correlation between the deployment of ID doctors and CNIC and the isolation rates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime- or levofloxacin-resistant Escherichia coli and Klebsiella pneumoinae, and meropenem-resistant Pseudomonas aeruginosa. Solely, the isolation rate of levofloxacin-resistant K. pneumoinae and the number of CNIC were statistically correlated (correlation coefficient = -0.33; p = 0.02), while the isolation rate of cefotaxime-resistant E. coli was paradoxically correlated with the number of ID doctors (correlation coefficient = 0.33; p = 0.02). Conclusions: Our macroscopic analysis using the open database was not a reliable method to evaluate the sufficiency of ID experts across the prefectures in Japan. A scheme to assess the appropriate distribution of ID experts should be developed.

DOI： 10.7759/cureus.16918

An Elderly Male with Primary Sjögren's Syndrome Presenting Pleuritis as the Initial Manifestation.

Yukichika Yamamoto, Yuki Otsuka, Takayuki Katsuyama, Yoshito Nishimura, Kosuke Oka, Kou Hasegawa, Hideharu Hagiya, Fumio Otsuka

Acta medica Okayama 75 ( 4 ) 539 - 542 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Primary Sjögren's syndrome (SS) is an autoimmune disease that usually affects the exocrine glands in mid-dle-aged women. Fifteen percent of SS patients experience severe systemic extraglandular complications, and pleuritis is one of the rare complications of SS. We report the case of an elderly Japanese man who initially pre-sented with a prolonged fever and chest pain and was finally diagnosed with primary SS-associated pleuritis. Of the nine reported cases of primary SS that initially presented with pleuritis, up to six cases were elderly males. This case highlights the complication of pleuritis among elderly males with primary SS.

DOI： 10.18926/AMO/62409

High-dose steroids for the treatment of severe COVID-19: comment. 国際誌

Shuichi Tanaka, Koichiro Yamamoto, Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka

Internal and emergency medicine 16 ( 5 ) 1415 - 1416 2021年8月

Effectiveness of supplemental oral calcium drink in preventing citrate-related adverse effects in peripheral blood progenitor cell collection. 国際誌

Keiko Fujii, Nobuharu Fujii, Takumi Kondo, Toshiharu Mitsuhashi, Makoto Nakamura, Keisuke Seike, Yasuhisa Sando, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Hiroyuki Sugiura, Fumio Otsuka, Yoshinobu Maeda

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 60 ( 4 ) 103147 - 103147 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis. Although the method for preventing severe adverse events is established, more efficient prophylaxis is required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January 2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.

DOI： 10.1016/j.transci.2021.103147

Pseudo-Cushing's state in a patient with non-functioning pituitary adenoma. 国際誌

Koichiro Yamamoto, Yoshihisa Hanayama, Fumio Otsuka

BMJ case reports 14 ( 7 ) 2021年7月

Trends in the nontuberculous mycobacterial disease mortality rate in Japan: A nationwide observational study, 1997-2016 国際誌

Ko Harada, Hideharu Hagiya , Tomoko Funahashi , Toshihiro Koyama, Mitsunobu R Kano, Fumio Otsuka

Clin Infect Dis. 73 ( 2 ) e321-e326 - E326 2021年7月

Acute Pancreatitis Related to COVID-19 Infection.

Koichiro Yamamoto, Kosuke Oka, Hiroyuki Sakae, Fumio Otsuka

Internal medicine (Tokyo, Japan) 60 ( 13 ) 2159 - 2160 2021年7月

Large-vessel Vasculitis Induced by Granulocyte Colony-Stimulating Factor Administration after Chemotherapy 国際誌

Koichiro Yamamoto, Nayu Tamura, Kosuke Oka, Kou Hasegawa, Hideharu Hagiya , Madoka Hokama, Joji Ishida, Fumio Otsuka

Mod Rheumatol Case Rep 5 ( 2 ) 322 - 326 2021年7月

Successful deceased donor kidney transplantation to a recipient with a history of COVID-19 treatment. 国際誌

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Kou Hasegawa, Takanori Sekito, Shuji Miyake, Shogo Watari, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Katsuyuki Tanabe, Hidemi Takeuchi, Yuri Nakashima, Masaru Kinomura, Herik Acosta, Yosuke Mitsui, Risa Kubota, Hirochika Nakajima, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Fumio Otsuka, Jun Wada, Yasutomo Nasu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1097 - 1101 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER

CASE PRESENTATION: A 49-year-old Asian male, who had undergone hemodialysis for >16 years, complained of a fever, dysgeusia and dysosmia, and was diagnosed with COVID-19 pneumonia based on severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (SARS-CoV-2 PCR) and computed tomography (CT). Treatment was started with oral favipiravir and ciclesonide inhalation. On the 10th day of treatment, the patient had a persistent high fever and a chest CT showed exacerbation of pneumonia, so dexamethasone was intravenously started. He was discharged after confirming two consecutive negative SARS-CoV-2 PCR tests. Three months after COVID-19 treatment, a SARS-CoV-2 PCR test was negative and he underwent a deceased donor kidney transplantation. Basiliximab induction with triple drug immunosuppression consisting of extended-release tacrolimus, mycophenolate mofetil and prednisolone, which is our regular immunosuppression protocol, was used. He was discharged on postoperative day 18 without the need for postoperative hemodialysis or any complications. The serum creatinine level was 1.72 mg/dL 95 days postoperatively and he had a favorable clinical course that was similar to deceased donor kidney recipients without a history of SARS-CoV-2 infection. CONCLUSION: We report the first case of a kidney transplantation after COVID-19 treatment in Japan and the fourth case globally. We would like to provide information about our successful case due to the anticipated increase in similar candidates in the near future.

DOI： 10.1016/j.jiac.2021.03.018

Deployment of Infectious Disease Experts and Prevalence of Antimicrobial Resistance in Okayama: A Call for Training of Specialists. 国際誌

Hideharu Hagiya, Koji Fujita, Shinya Kamiyama, Kazuki Ocho, Haruto Yamada, Fumio Otsuka

Cureus 13 ( 7 ) e16643 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CUREUS INC

Objective During the ongoing global pandemic of novel coronavirus disease 2019 (COVID-19), an emerging infectious disease, the implementation and execution of infection prevention and control (IPC) is of paramount importance. In this study, we aimed to assess the current deployment of infection control medical personnel in Okayama prefecture, who are supposed to play an essential role to prevent the outbreak of infectious diseases, and the current prevalence of antimicrobial-resistant (AMR) bacteria isolated in Okayama. Materials and methods This was a descriptive study using publicly available data. The numbers of infectious disease (ID)-doctors and the certified nurses in infection control (CNIC) per 100,000 population in 47 prefectures in Japan were calculated. We then compared the detected proportions of AMR pathogens among the prefectures in 2019 to be employed as a comparative parameter, which was obtained from Japan Nosocomial Infections Surveillance (JANIS) data. Results The number of ID-doctors was the 11th highest in Japan; however, they were unevenly distributed in southern Okayama, particularly at three tertiary hospitals. While the deployment of CNIC was geographically less uneven in the prefecture, their number was lower than the domestic average. According to the JANIS data, isolation rates of AMR pathogens were high in Okayama compared to other prefectures in Japan: vancomycin-resistant Enterococcus faecium (the third-worst); cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae (the third-worst and the second-worst, respectively); and meropenem-resistant Pseudomonas aeruginosa (the worst). Conclusions Our assessment provides underlying data and reinforces the need for educating multi-professional experts in the field of infectious diseases to prevent future public health threats in Okayama.

DOI： 10.7759/cureus.16643

Barium appendicitis. 国際誌

Daisuke Omura, Naoko Yunoki, Yuki Otsuka, Yasuhiro Nakano, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 9 ( 7 ) e04583 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

We have presented a case of barium appendicitis, which is a rare complication of barium enema studies. Barium sulfate is used widely for gastrointestinal radiographic studies and is associated with few complications. Clinicians need to be fully aware of this complication.

DOI： 10.1002/ccr3.4583

A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis. 国際誌

Yuki Otsuka, Hideharu Hagiya, Yasuhiro Nakano, Daisuke Omura, Kou Hasegawa, Haruto Yamada, Koji Iio, Tomoyuki Honda, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1126 - 1128 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER

The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect™ 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.

DOI： 10.1016/j.jiac.2021.05.001

Acute pancreatitis without abdominal pain induced by administration of nivolumab and ipilimumab. 国際誌

Koichiro Yamamoto, Kosuke Oka, Reina Son, Hiroyuki Honda, Hiroyuki Sakae, Kou Hasegawa, Shigeru Horiguchi, Hironari Kato, Osamu Yamasaki, Fumio Otsuka

Modern rheumatology case reports 5 ( 2 ) 425 - 430 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab are emerging agents for the treatment of cancers including melanoma. ICIs are known to cause immune-related adverse events (irAEs), including the development of enterocolitis, dermatitis, and nephritis. However, ICI-induced pancreatitis has seldom been reported, and its pathophysiology and clinical importance remain largely unknown. We describe a 76-year-old man with melanoma who developed acute pancreatitis without abdominal pain after immunotherapy with nivolumab and ipilimumab. The patient was referred due to 2-week-long general fatigue, anorexia, and dermatitis after his second immunotherapy. Laboratory examinations in serum showed high inflammation and renal dysfunction. Plain computed tomography (CT) on admission showed no new lesions including colitis or pancreatitis. On the 4th day of hospitalisation, serum pancreatic enzymes were extremely elevated. Amylase was increased to 683 U/L (normal range: 44-132) and lipase was increased to 1520 U/L (13-55), but he had no abdominal tenderness. Contrast-enhanced CT showed enlarged pancreatic parenchyma and magnetic resonance cholangiopancreatography showed peripancreatic fat stranding, suggesting pancreatitis. Blood culture tests and empirical antibiotic therapy with ceftriaxone indicated no active infectious diseases. We diagnosed ICI-induced pancreatitis and treated him with 0.5 mg/kg/day of prednisolone, which improved his general fatigue, anorexia, dermatitis, and pancreatitis. The potential significance of asymptomatic elevations of pancreatic enzymes has been unclear; however, this case suggested that ICI-induced pancreatitis without abdominal tenderness could be clinically significant. Clinicians should pay attention to the development of latent pancreatitis in patients receiving ICIs, even those without abdominal pain.

DOI： 10.1080/24725625.2021.1899444

ゴナドトロピン分泌調節における時計遺伝子およびBMPの関与

Preclinical diagnosis and identification of the chimeric CYP11B1/CYP11B2 gene in two pediatric cases of a Japanese family with glucocorticoid-remediable aldosteronism. 国際誌

Yasuhiro Nakano, Nahoko Iwata, Kanako Ogura-Ochi, Kosei Hasegawa, Akira Hirasawa, Fumio Otsuka

Hypertension research : official journal of the Japanese Society of Hypertension 44 ( 7 ) 891 - 893 2021年7月

副島佳晃, 岩田菜穂子, 須山敦仁, 中野靖浩, 山本紘一郎, 大塚文男

日本内分泌学会雑誌 97 ( 3 ) 640 - 640 2021年7月

NR5A1/NR5A2・ClockおよびBMPによる卵胞ステロイド合成調節メカニズムの検討

須山敦仁, 岩田菜穂子, 副島佳晃, 中野靖浩, 山本紘一郎, 大塚文男

日本内分泌学会雑誌 97 ( 3 ) 644 - 644 2021年7月

Involvement of BMP-15 in glucocorticoid actions on ovarian steroidogenesis by rat granulosa cells. 国際誌

Chiaki Kashino, Toru Hasegawa, Yasuhiro Nakano, Nahoko Iwata, Koichiro Yamamoto, Yasuhiko Kamada, Hisashi Masuyama, Fumio Otsuka

Biochemical and biophysical research communications 559 56 - 61 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

To elucidate the impact of glucocorticoids on ovarian steroidogenesis and its molecular mechanism by focusing on bone morphogenetic proteins (BMPs), we examined the effect of dexamethasone (Dex) on estradiol and progesterone synthesis by using primary culture of rat granulosa cells. It was revealed that Dex treatment dose-dependently decreased estradiol production but increased progesterone production induced by follicle-stimulating hormone (FSH) by granulosa cells. In accordance with the effects of Dex on estradiol synthesis, Dex suppressed P450arom mRNA expression and cAMP synthesis induced by FSH. Dex treatment in turn enhanced basal as well as FSH-induced levels of mRNAs encoding the enzymes for progesterone synthesis including P450scc and 3βHSD but not StAR and 20αHSD. Of note, Dex treatment significantly upregulated transcription of the BMP target gene Id-1 and Smad1/5/9 phosphorylation in the presence of BMP-15 among the key ovarian BMP ligands. It was also found that Dex treatment increased the expression level of BMP type-I receptor ALK-6 among the type-I and -II receptors for BMP-15. Inhibitory Smad6/7 expression was not affected by Dex treatment. On the other hand, BMP-15 treatment upregulated glucocorticoid receptor (GR) expression in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on ovarian steroidogenesis, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.

DOI： 10.1016/j.bbrc.2021.04.085

Hypothalamic Mass Detected in Langerhans Cell Histiocytosis

Ryosuke Takase, Yasuhiro Nakano, Shin Morizane, Fumio Otsuka

Intern. Med. 60 ( 11 ) 1795 - 1795 2021年6月

Isolated adrenocorticotropin deficiency induced by pembrolizumab for hypopharyngeal cancer: A case report. 国際誌

Koichiro Yamamoto, Kazuki Tokumasu, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 6 ) e04305 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

We report a case of isolated adrenocorticotropin deficiency caused by pembrolizumab. This condition can be fatal, but its rarity causes under-recognition. Oncologists should pay attention to adrenal insufficiency due to pembrolizumab.

DOI： 10.1002/ccr3.4305

Interrelationships Between Serum Levels of Procalcitonin and Inflammatory Markers in Patients Who Visited a General Medicine Department.

Jo Araki, Kosuke Oka, Koichiro Yamamoto, Yoshihisa Hanayama, Kazuki Tokumasu, Hideharu Hagiya, Hiroko Ogawa, Koichi Itoshima, Fumio Otsuka

Acta medica Okayama 75 ( 3 ) 299 - 306 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho=0.62), soluble interleukin-2 receptor (sIL-2R; rho=0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho=-0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

DOI： 10.18926/AMO/62221

Orbital mass and hairy kidney as characteristics of Erdheim-Chester disease. 国際誌

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 6 ) e04333 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, involving multiple organs. We report a case of ECD with typical features of an orbital mass and "hairy kidneys," whose recognition can lead to early diagnosis and treatment.

DOI： 10.1002/ccr3.4333

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease. 国際誌

Eriko Yasutomi, Toshihiro Inokuchi, Sakiko Hiraoka, Kensuke Takei, Shoko Igawa, Shumpei Yamamoto, Masayasu Ohmori, Shohei Oka, Yasushi Yamasaki, Hideaki Kinugasa, Masahiro Takahara, Keita Harada, Masaki Furukawa, Kouichi Itoshima, Ken Okada, Fumio Otsuka, Takehiro Tanaka, Toshiharu Mitsuhashi, Jun Kato, Hiroyuki Okada

Scientific reports 11 ( 1 ) 11086 - 11086 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE RESEARCH

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

DOI： 10.1038/s41598-021-90441-x

Clinical Manifestations of Patients with Influenza Differ by Age : A Prospective, Multi-centered Study in the Setouchi Marine Area.

Ryosuke Takase, Hideharu Hagiya, Hiroyuki Honda, Yasuhiro Nakano, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Yoshihisa Hanayama, Fumio Otsuka

Acta medica Okayama 75 ( 5 ) 567 - 574 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Influenza potentially has a high mortality rate when it affects the elderly. We aimed to examine the differences in clinical manifestations in patients with influenza according to their age. This multicenter prospective study was performed in six medical institutions in Okayama and Kagawa prefectures (Japan). Between December 1, 2019 and March 31, 2020, we collected data on adult patients diagnosed with influenza type A, who were strat-ified into younger (20-49 years), middle-aged (50-64 years), and older groups (≥ 65 years). We compared the presence or absence of fever, respiratory symptoms, and extrapulmonary symptoms according to age group. In total, 203 patients (113, younger; 51, middle-aged; and 39, older) were eligible for the analysis. The maxi-mum body temperature and temperature at first physician visit in the older group were significantly lower than those in the younger group. The incidence of respiratory symptoms was not different among the three groups. Chills, muscle pain, and arthralgia as systemic symptoms were noted significantly more frequently in the younger (80.9%) and middle-aged (75.5%) groups than in the older group (51.3%) (p = 0.002). Fever and sys-temic symptoms were less likely to appear in older patients, possibly resulting in the delaying of hospital visits among older adults.

DOI： 10.18926/AMO/62769

Droopy eyelid due to IgG4-related dacryoadenitis 国際誌

Ryosuke Takase, Hideharu Hagiya, Kazuki Tokumasu, Yoshito Nishimura, Atsunobu Sakurai, Kou Hasegawa, Yoshihisa Hanayama, Fumio Otsuka

Postgrad. Med. J 97 ( 1147 ) 333 - 334 2021年5月

Clinical Utility of the Ratio of Urinary Free Cortisol to Aldosterone as an Index for Inflammatory and Metabolic Dysregulation. 国際誌

Yuki Otsuka, Yasuhiro Nakano, Kazuki Tokumasu, Hiroyuki Honda, Mikako Obika, Kou Hasegawa, Yoshihisa Hanayama, Koichi Itoshima, Fumio Otsuka

Annals of clinical and laboratory science 51 ( 3 ) 352 - 358 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ASSOC CLINICAL SCIENTISTS

OBJECTIVE: Urinary free cortisol (UFC) is a reliable marker to avoid cortisol fluctuation and the effects of binding proteins. However, UFC levels are affected by fluid intake and urine volume, and the normal levels range widely. METHODS: To discover the utility of the ratio of urinary cortisol to aldosterone excretions, 246 patients in whom daily excretions of UFC and aldosterone (UAC) were measured were retrospectively analyzed. RESULTS: The UFC/UAC ratio showed significant positive and negative correlations with the levels of serum cortisol (R=0.287) and aldosterone (R=-0.762), respectively. The UFC/UAC ratio increased with aging in female patients, while it was not altered by the level of BMI in either gender. Markers for metabolic and inflammatory status, including hemoglobin A1c (R=0.327), albumin (R=-0.331), C-reactive protein (R=0.317), ferritin (R=0.473), and D-dimer (R=0.569), showed correlations with the ratio of UFC/UAC that were more significant than the correlations with the serum level of cortisol or UFC alone. Of note, the UFC/UAC ratio was shown to be an indicator for the risk of diabetes (AUC: 0.765), hypoalbuminemia (0.839), hyper-CRPemia (0.748), and thrombophilia (0.824), in which the cut-off levels of the UFC/UAC ratio were around 12. CONCLUSION: The UFC/UAC ratio is a variable for detecting metabolic and inflammatory complications related to adrenocortical dysfunction.

Pseudoacromegaly with acromegalic features in radiography. 国際誌

Koichiro Yamamoto, Kosuke Oka, Hiroyuki Honda, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 5 ) e04095 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Pseudoacromegaly is a condition characterized by acromegalic physical features without growth hormone excess, for which radiographic observation has seldom been reported. This is a rare case of pseudoacromegaly.

DOI： 10.1002/ccr3.4095

HIV-associated cerebral lymphoma in an elderly patient.

Yuki Otsuka, Hideharu Hagiya, Yasuhiro Nakano, Ryu Kimura, Kentaro Fujii, Fumio Otsuka

Geriatrics & gerontology international 21 ( 5 ) 435 - 436 2021年5月

どのように臨床研修医のモチベーションは上がるのか? プライマリ・ケア主体的診療の重要性

徳増一樹, 小比賀美香子, 尾原晴雄, 菊川誠, 大塚文男

日本プライマリ・ケア連合学会学術大会 12回 np637 - np637 2021年5月

周期的発熱、及び腹痛精査中に診断された正中弓状靱帯圧迫症候群の1例

乃美優孝, 井口俊博, 青山祐樹, 竹井健介, 安富絵里子, 井川翔子, 大森正泰, 岡昌平, 竹内桂子, 山崎泰史, 衣笠秀明, 原田馨太, 平岡佐規子, 岡田裕之, 徳増一樹, 大塚文男, 矢野修也, 菊地覚次, 坂本真樹

日本消化器病学会中国支部例会プログラム・抄録集 115回 83 - 83 2021年5月

Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells. 国際誌

Satoshi Fujisawa, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Takahiro Nada, Jun Wada, Fumio Otsuka

International journal of molecular sciences 22 ( 9 ) 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.

DOI： 10.3390/ijms22094553

Dysphagia Induced by Acromegalic Arthropathy

Manami Fujita, Yasuhiro Nakano, Hiroyuki Sakae, Fumio Otsuka

Intern Med 60 ( 7 ) 1127 - 1128 2021年4月

An adrenal incidentaloma caused by synchronous and isolated metastasis. 国際誌

Koichiro Yamamoto, Kosuke Oka, Hiroyuki Honda, Kou Hasegawa, Yoshihisa Hanayama, Tomofumi Watanabe, Yusuke Tominaga, Atsushi Takamoto, Takayuki Hara, Fumio Otsuka

Clinical case reports 9 ( 4 ) 2494 - 2495 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

We report a patient with adrenal incidentaloma due to synchronous and isolated metastasis from lung cancer, which is a relatively rare condition. Close checkups for incidentaloma in oncologic patients are mandatory, leading to successful operation.

DOI： 10.1002/ccr3.3996

Endogenous Bacterial Endophthalmitis Caused by Iliopsoas Abscess.

Weiying Sun, Yusuke Shiode, Kazuki Tokumasu, Shuhei Kimura, Mio Hosokawa, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Fumio Otsuka, Yuki Morizane

Acta medica Okayama 75 ( 2 ) 249 - 253 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

A 79-year-old woman presented to our hospital with a 10-day history of gradually worsening binocular vision and severe backache. Further investigations revealed poor bilateral best-corrected visual acuities (BCVA), bilateral vitreous opacities, gray-white lesions scattered throughout the retina, and a left iliopsoas abscess on CT that later grew out methicillin-sensitive S. aureus. The abscess was drained and intravenous antibiotics were initiated, but the left eye additionally required intravitreal vancomycin. BCVA for both eyes normalized within 1 year. Intramuscular abscess should be considered as a possible primary lesion in cases of endogenous bacterial endophthalmitis.

DOI： 10.18926/AMO/61909

Trends in the incidence and mortality of legionellosis in Japan: a nationwide observational study, 1999-2017. 国際誌

Shinnosuke Fukushima, Hideharu Hagiya, Yuki Otsuka, Toshihiro Koyama, Fumio Otsuka

Scientific reports 11 ( 1 ) 7246 - 7246 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PORTFOLIO

This study examined temporal trend, seasonality, and geographical variations of legionellosis incidence and mortality in Japan. This nationwide observational study used the Japanese Vital Statistics and Infectious Diseases Weekly Report (1999-2017) data to calculate legionellosis crude and age-adjusted incidence and mortality rates per 100,000 population by age and sex. Incidence was compared among the 4 seasons and regional incidence among 47 prefectures. Of 13,613 (11,194 men) people with legionellosis in Japan, 725 (569 men) were fatal. Increasing incidence trend occurred from 0.0004 (1999) to 1.37 (2017) per 100,000 population. People aged ≥ 70 years accounted for 43.1% overall; men's age-adjusted incidence rate was consistently approximately five times higher than for women. Significantly higher incidence occurred in summer than in winter (p = 0.013). Geographically, highest incidence (≥ 2.0 per 100,000 population) occurred in Hokuriku District, with increasing trends in Hokkaido and middle-part of Japan. Estimated fatality rates decreased consistently at 5.9% (95% confidence interval: - 8.1, - 3.5) annually, from 1999 to 2017, with no trend change point. Increasing legionellosis incidence occurred in Japan during 1999-2017, with declining estimated fatality rates. In this aging society and warming world, disease clinical burden may further deteriorate in future due to increasing incidence trends.

DOI： 10.1038/s41598-021-86431-8

Angina Simultaneously Diagnosed with the Recurrence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. 国際誌

Koki Li, Yuki Otsuka, Yasuhiro Nakano, Daisuke Omura, Kou Hasegawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Diagnostics (Basel, Switzerland) 11 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) mainly affects young adults and can have a potential impact on social functioning. As this syndrome is associated with endothelial dysfunction, the heart can be damaged via ischemia due to endothelial damage. This might potentially lead to heart failure, which accounts for approximately 20% of deaths among patients with ME/CFS. While cardiac ischemia is thought be a pathophysiologically important manifestation of this syndrome, this is not yet reported. Herein, we present a case of a young female with newly diagnosed vasospastic or microvascular angina and concurrent exacerbation of ME/CFS severity. Her anginal symptoms, including exertional chest pain and transient chest discomfort, mimicked those of ME/CFS but were relieved after the administration of a calcium channel blocker. We emphasize the possibility of concurrent angina and exacerbation of ME/CFS and the importance of detecting cardiac ischemia to avoid unfavorable outcomes.

DOI： 10.3390/diagnostics11030460

Burnout of Healthcare Workers amid the COVID-19 Pandemic: A Japanese Cross-Sectional Survey. 国際誌

Yoshito Nishimura, Tomoko Miyoshi, Hideharu Hagiya, Yoshinori Kosaki, Fumio Otsuka

International journal of environmental research and public health 18 ( 5 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI

The coronavirus disease 2019 (COVID-19) global pandemic has drastically changed how we live and work. Amid the prolonged pandemic, burnout of the frontline healthcare professionals has become a significant concern. We conducted a cross-sectional survey study to provide data about the relationship between the COVID-19 pandemic and the prevalence of burnout in healthcare professionals in Japan. Healthcare workers in a single Japanese national university hospital participated in the survey, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks and the Maslach Burnout Inventory. Of those, 25.4% fully answered the survey; 33.3% were doctors and 63.6% were nurses, and 36.3% engaged in care of COVID-19 patients in the past 2 weeks. Compared to those belonging to General Medicine, those in Emergency Intensive Care Unit were at higher risk of burnout (odds ratio (OR), 6.7; 95% CI, 1.1-42.1; p = 0.031). Of those who engaged in care of COVID-19 patients, 50% reported burnout while 6.1% did not (OR 8.5, 95% CI; 1.3-54.1; p = 0.014). The burnout of healthcare workers is a significant concern amid the pandemic, which needs to be addressed for sustainable healthcare delivery.

DOI： 10.3390/ijerph18052434

Ulcer-like Projection Accompanied by Giant Cell Arteritis

Yuki Otsuka, Kosuke Oka, Yoshihisa Hanayama, Fumio Otsuka

Intern Med 60 ( 5 ) 819 - 820 2021年3月

総合内科診療に潜む内分泌代謝疾患

大塚文男, 小比賀美香子, 長谷川功, 中野靖浩, 徳増一樹

日本内科学会雑誌 110 ( 3 ) 486 - 491 2021年3月

Gingival lesion leading to a diagnosis of angiosarcoma.

Yasuhiro Nakano, Yosuke Sazumi, Yuki Mizuta, Hiroyuki Sakae, Fumio Otsuka

Journal of general and family medicine 22 ( 2 ) 90 - 91 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

A man who presented with a gingival tumor was finally diagnosed with angiosarcoma. It is important for primary care physicians to perform checkups of the oral cavity since oral lesions can lead to a diagnosis of serious systemic diseases.

DOI： 10.1002/jgf2.397

Simultaneous hot and cold thyroid nodules: Which is malignant? 国際誌

Yuki Otsuka, Yasuhiro Nakano, Daisuke Omura, Takayuki Iwamoto, Ruiko Hayashi, Fumio Otsuka

Clinical case reports 9 ( 3 ) 1810 - 1811 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Physicians should be aware of the risk of malignancy in patients with toxic multinodular goiter. Radionuclide scan cannot be used to predict the malignant potential of thyroid nodules. A comprehensive evaluation of imaging studies is needed.

DOI： 10.1002/ccr3.3843

Left-sided appendicitis due to situs inversus totalis. 国際誌

Yuki Otsuka, Ruiko Hayashi, Shinichi Urano, Akihide Yashima, Yasuo Nanba, Fumio Otsuka

Clinical case reports 9 ( 3 ) 1791 - 1792 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Situs inversus may mimic the pain localization of acute abdomen. In patients with acute abdomen, especially elderly patients who are medically healthy, physicians should cautiously diagnose the etiology of acute abdomen in combination with imaging studies.

DOI： 10.1002/ccr3.3734

Involvement of clock gene expression, bone morphogenetic protein and activin in adrenocortical steroidogenesis by human H295R cells

Yoshiaki Soejima, Nahoko Iwata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Takahiro Nada, Hiroko Ogawa, Fumio Otsuka

Endocr J 68 ( 2 ) 243 - 250 2021年2月

Impact of the COVID-19 Pandemic on the Psychological Distress of Medical Students in Japan: Cross-sectional Survey Study. 国際誌

Yoshito Nishimura, Kanako Ochi, Kazuki Tokumasu, Mikako Obika, Hideharu Hagiya, Hitomi Kataoka, Fumio Otsuka

Journal of medical Internet research 23 ( 2 ) e25232 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JMIR PUBLICATIONS, INC

BACKGROUND: The COVID-19 pandemic has negatively affected medical education. However, little data are available about medical students' distress during the pandemic. OBJECTIVE: This study aimed to provide details on how medical students have been affected by the pandemic. METHODS: A cross-sectional study was conducted. A total of 717 medical students participated in the web-based survey. The survey included questions about how the participants' mental status had changed from before to after the Japanese nationwide state of emergency (SOE). RESULTS: Out of 717 medical students, 473 (66.0%) participated in the study. In total, 29.8% (141/473) of the students reported concerns about the shift toward online education, mostly because they thought online education would be ineffective compared with in-person learning. The participants' subjective mental health status significantly worsened after the SOE was lifted (P<.001). Those who had concerns about a shift toward online education had higher odds of having generalized anxiety and being depressed (odds ratio [OR] 1.97, 95% CI 1.19-3.28) as did those who said they would request food aid (OR 1.99, 95% CI 1.16-3.44) and mental health care resources (OR 3.56, 95% CI 2.07-6.15). CONCLUSIONS: Given our findings, the sudden shift to online education might have overwhelmed medical students. Thus, we recommend that educators inform learners that online learning is not inferior to in-person learning, which could attenuate potential depression and anxiety.

DOI： 10.2196/25232

Positron emission tomography for the diagnosis of prosthetic heart valve endocarditis. 国際誌

Yuki Otsuka, Hideharu Hagiya, Kosuke Oka, Fumio Otsuka

BMJ case reports 14 ( 2 ) 2021年2月

Septic pulmonary emboli caused by Tsukamurella inchonensis: A case report 国際誌

Kazuyoshi Gotoh , I Putu Bayu Mayura, Hideharu Hagiya, Kyoichi Obata, Tatsuo Ogawa, Koji Iio, Takumi Fujimori, Fumio Otsuka, Osamu Matsushita

J Infect Chemother 27 ( 2 ) 369 - 372 2021年2月

Clinical Characteristics of Low Androgen Status in Males with Type 2 Diabetes Mellitus.

Jun Hamahara, Hiroyuki Honda, Koichiro Yamamoto, Kazuki Tokumasu, Yoshihisa Hanayama, Hideharu Hagiya, Mikako Obika, Keigo Ueda, Masayuki Kishida, Fumio Otsuka

Acta medica Okayama 75 ( 1 ) 1 - 8 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 ± 1.5 years old), decreases in serum FT levels to < 8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The per-centages of patients with low FT levels were high in the ≥ 50 years age group (83%), the HbA1c < 7% group (67%), and the 25 ≤ BMI < 30 kg/m2 group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R = 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = -0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R = 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males.

DOI： 10.18926/AMO/61424

複数の基礎疾患を有した超高齢者COVID-19の一例

孫麗那, 藤田茉奈美, 山本紘一郎, 岡浩介, 山根真衣, 大塚勇輝, 高瀬了輔, 中野靖浩, 大村大輔, 榮浩行, 長谷川功, 萩谷英大, 大塚文男

日本病院総合診療医学会雑誌 17 ( 臨増1 ) 149 - 149 2021年2月

COVID-19外国人患者の受入れで明らかとなった課題と病院総合医に求められる役割

大塚勇輝, 大村大輔, 李皓生, 藤田茉奈美, 山根真衣, 山本紘一郎, 孫麗那, 高瀬了輔, 中野靖浩, 岡浩, 榮浩行, 徳増一樹, 長谷川功, 萩谷英大, 小比賀美香子, 片岡仁美, 大塚文男

日本病院総合診療医学会雑誌 17 ( 臨増1 ) 109 - 109 2021年2月

COVID-19外国人患者の受入れで明らかとなった課題と病院総合医に求められる役割

日本病院総合診療医学会雑誌 17 ( 臨増1 ) 109 - 109 2021年2月

De-escalation concept and MIC literacy among medical students and clinical residents. 国際誌

Hideharu Hagiya, Kazuki Tokumasu, Mikako Obika, Fumio Otsuka

Postgraduate medical journal 98 ( e3 ) e183-e184 2021年1月

Without a silhouette. 国際誌

Yosuke Sazumi, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 9 ( 1 ) 574 - 575 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Primary effusion lymphoma (PEL) is a kind of malignant lymphoma that develops without a tumor mass. A fluid smear is of no use for the diagnosis of miscellaneous condition. Repeated cell-block smear with immunostaining is useful for the diagnosis of PEL.

DOI： 10.1002/ccr3.3469

Antimicrobial prescription practices for outpatients with acute respiratory tract infections: A retrospective, multicenter, medical record-based study. 国際誌

Tomoharu Ishida, Hideharu Hagiya, Hiroyuki Honda, Yasuhiro Nakano, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Yoshihisa Hanayama, Fumio Otsuka

PloS one 16 ( 11 ) e0259633 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Antimicrobial stewardship for outpatients with acute respiratory tract infections (ARTIs) should be urgently promoted in this era of antimicrobial resistance. Previous large-sample studies were based on administrative data and had limited reliability. We aimed to identify current antimicrobial prescription practices for ARTIs by directly basing on medical records. This multicenter retrospective study was performed from January to December in 2018, at five medical institutes in Japan. We targeted outpatients aged ≥18 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting ARTIs. We divided the eligible cases into three age groups (18-64 years, 65-74 years, and ≥75 years). We defined broad-spectrum antimicrobials as third-generation cephalosporins, macrolides, fluoroquinolones, and faropenem. Primary and secondary outcomes were defined as the proportion of antimicrobial prescriptions for the common cold and other respiratory tract infections, respectively. Totally, data of 3,940 patients were collected. Of 2,914 patients with the common cold, 369 (12.7%) were prescribed antimicrobials. Overall, compared to patients aged ≥75 years (8.5%), those aged 18-64 years (16.6%) and those aged 65-74 years (12.1%) were frequently prescribed antimicrobials for the common cold (odds ratio [95% confidential interval]; 2.15 [1.64-2.82] and 1.49 [1.06-2.09], respectively). However, when limited to cases with a valid diagnosis of the common cold by incorporating clinical data, no statistical difference was observed among the age groups. Broad-spectrum antimicrobials accounted for 90.2% of the antimicrobials used for the common cold. Of 1,026 patients with other respiratory infections, 1,018 (99.2%) were bronchitis, of which antimicrobials were prescribed in 49.9% of the cases. Broad-spectrum antimicrobials were the main agents prescribed, accounting for nearly 90% of prescriptions in all age groups. Our data suggested a favorable practice of antimicrobial prescription for outpatients with ARTIs in terms of prescribing proportions, or quantitative aspect. However, the prescriptions were biased towards broad-spectrum antimicrobials, highlighting the need for further antimicrobial stewardship in the outpatient setting from a qualitative perspective.

DOI： 10.1371/journal.pone.0259633

Recurrence of Hypoglycemic Coma in a Patient with Anorexia Nervosa.

Koichiro Yamamoto, Daisuke Omura, Mai Yamane, Reina Son, Kou Hasegawa, Hiroyuki Honda, Mikako Obika, Nozomu Minao, Satoru Edahiro, Norihito Yamada, Fumio Otsuka

Acta medica Okayama 75 ( 5 ) 631 - 636 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Anorexia nervosa (AN) is occasionally complicated with hypoglycemic coma, which may cause sudden death by unknown mechanisms. We present the case of a 36-year-old woman with recurrent comas and a nineteen-year history of AN. She was found in a coma with remarkable hypoglycemia (28 mg/dL). Her BMI was 11.1 kg/m2. Endocrine workup revealed extremely low serum levels of glucagon, IGF-I and insulin. Asymptomatic hypoglycemia occurred with liver injury in the refeeding process. An aberrant glucose metabolism due to liver damage might have been involved in her susceptibility to hypoglycemia. This case suggests a possible mechanism of hypoglycemic coma in AN.

DOI： 10.18926/AMO/62776

Therapeutic Drug Monitoring for Aminoglycosides: Not Yet Readily Available in Japanese University Hospitals

Salivary gland enlargement manifested in recurred acromegaly

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Tomoko Miyoshi, Mikako Obika, Hiroko Ogawa, Hitomi Kataoka, Fumio Otsuka

JOURNAL OF HOSPITAL GENERAL MEDICINE 3 ( 1 ) 36 - 37 2021年

Campylobacter jejuni enteritis mimicking colon cancer

Masayuki Kagota, Kosuke Oka, Hideharu Hagiya, Fumio Otsuka

JOURNAL OF HOSPITAL GENERAL MEDICINE 3 ( 6 ) 224 - 224 2021年

Extreme Hyperferritinemia due to Alcoholic Liver Disease：Secondary Hemochromatosis

Koichiro Yamamoto, Yoshito Nishimura, Mai Yamane, Reina Son, Daisuke Omura, Kou Hasegawa, Youhei Marukawa, Fumio Otsuka

JOURNAL OF HOSPITAL GENERAL MEDICINE 3 ( 1 ) 33 - 35 2021年

Electrocardiography diagnosed severe hypokalaemia in anorexia nervosa

Yuki Otsuka, Yasuhiro Nakano, Kazuki Tokumasu, Fumio Otsuka

JOURNAL OF HOSPITAL GENERAL MEDICINE 3 ( 2 ) 59 - 60 2021年

Hideharu Hagiya, Fumio Otsuka

JMA Journal 5 ( 1 ) 127 - 129 2021年

Intra-arterial gas, a clue for diagnosis of peri-aortic inflammation due to infection 国際誌

Daisuke Omura, Masatoshi Ogata, Yoshio Sakane, Ryuichi Matsuo, Harushige Nakatsukasa, Hideharu Hagiya, Fumio Otsuka

Clin. Case Rep. 8 ( 12 ) 3619 - 3620 2020年12月

A rare complication: Infection in acromegalic renal cysts. 国際誌

Yuki Mori, Yuki Otsuka, Yasuhiro Nakano, Hiroyuki Sakae, Kou Hasegawa, Fumio Otsuka

Clinical case reports 8 ( 12 ) 3551 - 3552 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Renal cysts are detected in one third of acromegaly patients, especially in uncontrolled cases. Clinicians should pay attention to unexpected infection of enlarged renal cysts in acromegaly patients.

DOI： 10.1002/ccr3.3108

Clinical Application of the Ratio of Serum Bone Isoform to Total Alkaline Phosphatase in General Practice

Yuya Yokota, Yoshito Nishimura, Akemi Ando, Yoshihisa Hanayama, Kou Hasegawa, Hideharu Hagiya, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Fumio Otsuka

Acta Med. Okayama 74 ( 6 ) 467 - 474 2020年12月

Clinical relevance of insulin-like growth factor-1 to cardiovascular risk markers 国際誌

Harada K, Hanayama Y, Obika M, Itoshima K, Okada K, Otsuka F

Aging Male 23 ( 5 ) 1030 - 1038 2020年12月

Involvement of serum dehydroepiandrosterone sulfate in erythropoietic activity．国際誌

Harada K, Hanayama Y, Obika M, Itoshima K, Okada K, Otsuka F

Aging Male 23 ( 5 ) 756 - 763 2020年12月

Effects of somatostatin analogs on catecholamine biosynthesis regulated by corticosteroids and bone morphogenetic proteins in rat pheochromocytoma cells

Takahiro Nada, Motoshi Komatsubara, Nahoko Iwata, Yasuhiro Nakano, Fumio Otsuka

2020年12月

Comparison of the Clinico-Microbiological Characteristics of Culture-Positive and Culture-Negative Septic Pulmonary Embolism: A 10-Year Retrospective Study 国際誌

Yoshito Nishimura, Hideharu Hagiya, Mikako Obika , Fumio Otsuka

Pathogens 9 ( 12 ) 9 - 12 2020年11月

Adult-onset Still's disease accompanying noninfective endocarditis.

Kosuke Oka, Yokota Yuya, Miho Yasuda, Fumio Otsuka

Journal of general and family medicine 21 ( 6 ) 268 - 269 2020年11月

Ectopic hyperparathyroidism due to an auto-transplanted parathyroid gland 国際誌

Ko Harada, Fumio Otsuka

Clin. Case Rep 8 ( 11 ) 2312 - 2313 2020年11月

Massive pheochromocytoma. 国際誌

Terumitsu Anai, Kosuke Oka, Yuya Yokota, Yoshito Nishimura, Hideharu Hagiya, Fumio Otsuka

Clinical case reports 8 ( 11 ) 2308 - 2309 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Complications of pheochromocytoma, such as hypertensive emergency, can be critical. Clinicians should recognize that pheochromocytoma is not uncommon in patients with large adrenal tumors, and screening should be undertaken prior to any intervention.

DOI： 10.1002/ccr3.3124

Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once-weekly somapacitan or daily growth hormone 国際誌

Fumio Otsuka, Yutaka Takahashi, Shigeyuki Tahara, Yoshihisa Ogawa, Michael H?jby Rasmussen, Koji Takano

Clin. Endocrinol. 93 ( 5 ) 620 - 628 2020年11月

Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation (vol 60, pg 473, 2020)

Keisuke Seike, Nobuharu Fujii, Naomi Asano, Shigenori Ohkuma, Yasushi Hirata, Keiko Fujii, Yasuhisa Sando, Makoto Nakamura, Kazunori Naito, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-ichi Matsuoka, Kazuo Tsubaki, Fumio Otsuka, Yoshinobu Maeda

TRANSFUSION 60 ( 11 ) 2765 - 2765 2020年11月

Localized Lymph Node Light Chain Amyloidosis

Akira Yamamoto, Nobuharu Fujii, Mikako Obika, Taro Yamashita, Fumio Otsuka

Intern. Med 59 ( 19 ) 2415 - 2418 2020年10月

Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients

Koichiro Yamamoto, Yoshihisa Hanayama, Kou Hasegawa, Kazuki Tokumasu, Tomoko Miyoshi , Hideharu Hagiya, Hiroko Ogawa, Mikako Obika, Koichi Itoshima, Fumio Otsuka

Acta Med. Okayama 74 ( 5 ) 381 - 389 2020年10月

Generation of four induced pluripotent stem cell lines (FHUi003-A, FHUi003-B, FHUi004-A and FHUi004-B) from two affected individuals of a familial neurohypophyseal diabetes insipidus family 国際誌

Satoru Yoshida, Hanayuki Okura, Hidetaka Suga, Mika Soen, Yohei Kawaguchi, Junki Kurimoto, Takashi Miyata, Hiroshi Takagi, Hiroshi Arima, Tatsuya Fujikawa, Fumio Otsuka, Akifumi Matsuyama

Stem Cell Res 48 101960 - 101960 2020年10月

Aldosterone enhances progesterone biosynthesis regulated by bone morphogenetic protein in rat granulosa cells 国際誌

Yasuhiro Nakano, Toru Hasegawa, Chiaki Kashino, Nahoko Iwata, Koichiro Yamamoto, Atsuhito Suyama, Yoshiaki Soejima, Takahiro Nada, Fumio Otsuka

J Steroid Biochem Mol Biol 203 105738 - 105738 2020年10月

Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome 国際誌

Kosuke Oka, Mai Yamane, Yuya Yokota, Miho Yasuda, Kou Hasegawa, Takumi Fujimori , Koji Iio, Hideharu Hagiya, Fumio Otsuka

J. Infect. Chemother. 26 ( 10 ) 1095 - 1099 2020年10月

Antibiotic literacy among Japanese medical students. 国際誌

Hideharu Hagiya, Hideo Ino, Kazuki Tokumasu, Hiroko Ogawa, Tomoko Miyoshi, Kanako Ochi, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 26 ( 10 ) 1107 - 1109 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER

Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship.

DOI： 10.1016/j.jiac.2020.06.021

A nationwide trend analysis in the incidence and mortality of Creutzfeldt-Jakob disease in Japan between 2005 and 2014 国際誌

Yoshito Nishimura, Ko Harada, Toshihiro Koyama, Hideharu Hagiya , Fumio Otsuka

Sci Rep 10 ( 1 ) 15509 - 15509 2020年9月

Hashimoto's hyroiditis and primary thyroid lymphoma 国際誌

Y Otsuka, M Yasuda, K Tokumasu, K Hasegawa, F Otsuka

QJM 0 ( 0 ) 691 - 692 2020年9月

Bilateral massive empyema with bronchopleural fistula．国際誌

Harada K, Hagiya H, Otsuka F

Postgrad. Med. J. 96 ( 1139 ) 573 - 573 2020年9月

Hepatic encephalopathy due to extrahepatic portosystemic shunt 国際誌

Yosuke Sazumi, Yoshito Nishimura, Yuki Otsuka, Yuki Mizuta, Yasuhiro Nakano, Hiroyuki Sakae, Fumio Otsuka

Clin. Case Rep 8 ( 9 ) 1852 - 1853 2020年9月

Calcinosis Cutis 国際誌

Ko Harada, Ei Miyasaka, Fumio Otsuka

Am. J. Med 133 ( 9 ) e528-e529 - E529 2020年9月

A rare case of oncocytic adrenocortical carcinoma clinically presented as an incidentaloma

Ko Harada, Miho Yasuda, Yasuhiro Nakano, Kazuhiro Yoshida, Yuzo Umeda, Takahito Yagi, Yuto Yamazaki , Hironobu Sasano, Fumio Otsuka

Endocr. J. 67 ( 8 ) 883 - 888 2020年8月

Multiple Deep-seated Dentofacial Abscesses Caused by Multidrug-resistant Viridans Group Streptococci

Shinnosuke Fukushima, Hideharu Hagiya, Yuki Mizuta, Yasuhiro Nakano, Masahiro Takahara, Kayo Okamoto, Yuko Hayashi , Kiyoshi Yamada, Kou Hasegawa, Fumio Otsuka

Intern. Med 59 ( 16 ) 2067 - 2070 2020年8月

Coronary Spastic Angina Induced by Adrenal Insufficiency

Yuki Otsuka, Ko Harada, Miho Yasuda, Yasuhiro Nakano, Kou Hasegawa, Fumio Otsuka

Intern. Med 59 ( 15 ) 1873 - 1877 2020年8月

Mycobacterium chelonae bloodstream infection induced by osteomyelitis of toe: A case report 国際誌

Yayoi Ueda, Kazuki Tokumasu, Hideharu Hagiya, Koji Iio, Takumi Fujimori, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Fumio Otsuka

J. Infect. Chemother. 26 ( 8 ) 843 - 846 2020年8月

Invasive non-typeable Haemophilus influenzae infection due to endometritis associated with adenomyosis 国際誌

Yoshito Nishimura, Hideharu Hagiya, Kaoru Kawano, Yuya Yokota, Kosuke Oka, Koji Iio , Kou Hasegawa, Mikako Obika, Tomoko Haruma, Sawako Ono, Hisashi Masuyama, Fumio Otsuka

BMC Infec. Dis 20 ( 1 ) 521 - 521 2020年7月

Clinical and biochemical characteristics of patients having general symptoms with increased serum IgG4．国際誌

Hasegawa K, Hanayama Y, Obika M, Miyoshi T, Ogawa H, Kondo E, Kataoka H, Sato Y, Otsuka F

Mod Rheumatol 30 ( 4 ) 721 - 728 2020年7月

Vision loss, tractional retinal detachment, and profound anemia due to rectal carcinoma 国際誌

Akira Yamamoto, Yoshito Nishimura, Mikako Obika, Yuki Morizane, Fumio Otsuka

Clin. Case Rep 8 ( 7 ) 1304 - 1305 2020年7月

Macromolecules detected in highly increased serum luteinizing hormone

K Ogura-Ochi, K Itoshima, Y Kamada, F Otsuka

J. Endocrinol. Invest. 856 - 866 2020年6月

X-linked Hypophosphatemia (XLH) Mimicking Rheumatic Disease 査読

Ryosuke Takase, Yasuhiro Nakano, Kosei Hasegawa, Fumio Otsuka

Intern. Med. 59 ( 9 ) 1233 - 1234 2020年5月

Rigid Ears and Hyperpigmentation in Addison's Disease 国際誌

Ko Harada, Fumio Otsuka

Am. J. Med. 133 ( 5 ) e192 2020年5月

An Endoscopic Biopsy Specimen Contains Adequate Lymphocytes for Flow Cytometric Analysis of Light Chain Expression in the Gastrointestinal Mucosa 国際誌

Masaya Iwamuro, Katsunori Matsueda, Takahide Takahashi, Sizuma Omote, Takehiro Tanaka, Daisuke Ennishi, Fumio Otsuka, Tadashi Yoshino, Hiroyuki Okada

Ann. Clin. Lab. Sci. 50 ( 3 ) 348 - 353 2020年5月

Cardiac mucosa-associated lymphoid tissue lymphoma in IgG4-related disease．国際誌

Harada K, Otsuka F

Euro Heart J. 41 ( 15 ) 1519 - 1519 2020年4月

Malignant Lymphoma Developed in the Hypothalamus

Ryosuke Takase, Yasuhiro Nakano, Fumio Otsuka

Intern. Med. 59 ( 7 ) 1009 - 1010 2020年4月

Gastrointestinal: Massive right pleural effusion caused by a pancreaticopleural fistula

K Tokumasu, K Harada, F Otsuka

J. Gastroenterol. Hepatol. 525 2020年4月

Observer agreement for the diagnosis of intestinal acute graft-vs.-host disease based on the presence of villous atrophy in the terminal ileum 国際誌

Yuusaku Sugihara, Sakiko Hiraoka, Eriko Yasutomi , Shohei Oka, Yasushi Yamasaki, Toshihiro Inokuchi , Hideaki Kinugasa, Masahiro Takahara, Yuki Morito, Sakuma Takahashi, Keita Harada, Takehiro Tanaka, Fumio Otsuka, Hiroyuki Okada

Exp. Ther. Med 19 ( 4 ) 3076 - 3080 2020年4月

Albright’s Hereditary Osteodystrophy

Ko Harada , Fumio Otsuka

QJM 2020年3月

Osmotic Demyelination Syndrome Triggered by Pituitary Apoplexy

Yuya Yokota, Kosuke Oka, Miho Yasuda, Fumio Otsuka

Intern. Med 59 ( 6 ) 869 - 870 2020年3月

Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation 国際誌

Keisuke Seike, Nobuharu Fujii, Naomi Asano, Shigenori Ohkuma, Yasushi Hirata, Keiko Fujii, Yasuhisa Sando, Makoto Nakamura, Kazunori Naito, Kyosuke Saeki, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka , Kazuo Tsubaki, Fumio Otsuka, Yoshinobu Maeda

Transfusion. 60 ( 3 ) 473 - 478 2020年3月

Calciphylaxis of the fingers

Ko Harada, Jo Araki, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

J Gen Fam Med. 21 ( 2 ) 25 - 26 2020年3月

A Comparison of the Clinical Characteristics of TAFRO Syndrome and Idiopathic Multicentric Castleman Disease in General Internal Medicine: A 6-Year Retrospective Study．国際誌

Nishimura Y, Hanayama Y, Fujii N, Kondo E, Otsuka F

Intern. Med. J. 50 ( 2 ) 184 - 191 2020年2月

Clinical Relevance of Blood Glucose and Gastroesophageal Reflux Symptoms to Depressive Status in Patients with Type 2 Diabetes Mellitus

Hiroyuki Honda, Yoshihisa Hanayama, Mikako Obika, Kou Hasegawa, Jun Hamahara, Masayuki Kishida , Hideharu Hagiya, Hiroko Ogawa, Hitomi Kataoka, Fumio Otsuka

Acta Med Okayama 74 ( 1 ) 33 - 40 2020年2月

繰り返しセルブロック標本を作製することにより原発性滲出性リンパ腫様リンパ腫と診断した1例

長谷井稜子, 佐住洋祐, 徳増一樹, 長谷川功, 萩谷英大, 藤井伸治, 花山宜久, 大塚文男

日本病院総合診療医学会雑誌 16 ( 臨増1 ) 166 - 166 2020年2月

数年来,慢性疲労症候群として加療されていたACTH単独欠損症の1例

筒井ほのか, 徳増一樹, 原田洸, 安田美帆, 長谷川功, 萩谷英大, 花山宜久, 大塚文男

日本病院総合診療医学会雑誌 16 ( 臨増1 ) 113 - 113 2020年2月

Panda and lambda sign' in sarcoidosis

K Harada, M Yasuda, F Otsuka

QJM 113 ( 1 ) 61 - 62 2020年1月

Purple Urine Bag Syndrome.

Ko Harada, Chihiro Hiraiwa, Ei Miyasaka and Fumio Otsuka

J. Hosp. Gen. Med. 2020年1月

Dysgeusia in a Psychiatric Patient: A Case of Chronic Lithium Intoxication.

Harada K, Tokumasu K, Hagiya H, Obika M and Otsuka F:

J. Hosp. Gen. Med. 116 - 120 2020年1月

Technique for single-step lymphocyte isolation from an endoscopic biopsy specimen for the diagnosis of gastrointestinal lymphoma 国際誌

Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Sizuma Omote, Katsunori Matsueda, Takehiro Tanaka, Daisuke Ennishi, Fumio Otsuka, Tadashi Yoshino, Hiroyuki Okada

MethodsX 7 101095 - 101095 2020年

Correlations between depressive conditions and gastroesophageal reflux symptoms in patients visiting a department of general medicine．

Suganami Y, Oka K, Hanayama Y, Honda H, Hamahara J, Obika M, Kariyama K, Kishida M, Otsuka F

Acta Med. Okayama 73 ( 6 ) 479 - 486 2019年12月

“Small Heart Syndrome” with orthostatic hypotension．

Harada K, Yasuda M, Otsuka F

Intern. Med. 58 ( 22 ) 3337 - 3338 2019年11月

Risk Factors for Low Bone Mineral Density Determined in Patients in a General Practice Setting．

Ando A, Mitsuhashi T, Honda M, Hanayama Y, Hasegawa K, Obika M, Kataoka H, Otsuka F

Acta Med.Okayama 73 ( 5 ) 403 - 411 2019年10月

Feasibility of flow cytometric analysis of restricted light chain in endoscopic biopsy specimens from patients with gastrointestinal tract B cell lymphoma: a pilot study．国際誌

Matsueda A, Iwamuro M, Takahashi T, Omote S, Nishida K, Tanaka T, Ennishi D, Otsuka F

BMC Res Notes. 12 ( 1 ) 571 - 571 2019年9月

A case of pseudo-pheochromocytoma possibly induced by a preceding respiratory infection．

Hagiya H, Nakagami F, Yoshida S, Nagawasa M, Takami Y, Akasaka H, Yamamoto K, Otsuka F, Rakugi H

J. Hosp. Gen. Med. 1 ( 3 ) 16 - 20 2019年9月

Myxedema coma accompanied by sick sinus syndrome and hypoventilation: a case report．

Harada K, Murakami S, Tokumasu K, Togawa Y, Otsuka F

J. Gen. Fam. Med. 20 ( 5 ) 206 - 208 2019年9月

A novel case of myxoid variant of adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1．

Harada K, Yasuda M, Hasegawa K, Yamazaki Y, Sasano H, Otsuka F

Endocr. J. 66 ( 8 ) 739 - 744 2019年8月

FDG uptake in toxic multinodular goiter．

Ocho K, Hasegawa K, Otsuka F

J. Hosp. Gen. Med. 1 ( 2 ) 14 - 15 2019年7月

Factors Related to Burnout in Resident Physicians in Japan．国際誌

Nishimura Y, Miyoshi T, Obika M, Ogawa H, Kataoka H, Otsuka F

Int. J. Med. Educ. 10 129 - 135 2019年7月

Swollen hands and “fist sign” in acromegaly．国際誌

Harada K, Hasegawa K, Otsuka F

Am. J. Med. 132 ( 7 ) e618-e619 - E619 2019年7月

A huge liver cyst manifesting dyspnea and edema．

Nagao S, Iwamuro M, Shiraha H, Otsuka F

Intern. Med. 58 ( 12 ) 1811 - 1812 2019年6月

Histidine-Rich Glycoprotein Augments Natural Killer Cell Function by Modulating PD-1 Expression via CLEC-1B．国際誌

Nishimura Y, Wake H, Teshigawara K, Wang D, Sakaguchi M, Otsuka F, Nishibori M

Pharmacol Res Perspect 7 ( 3 ) e00481 - e00481 2019年6月

Anterior Cutaneous Nerve Entrapment Syndrome Possibly Triggered by Oral Contraceptives．

Omura D, Obika M, Iwamuro M, Nagao S, Nada T, Matsuzaki T, Kondo Y, Otsuka F

Intern. Med 58 ( 10 ) 1507 - 1509 2019年5月

Retention cysts due to latent pancreatic cancer．

Oka K, Horiguchi S, Obika M, Otsuka F

J. Hosp. Gen. Med. ( 1 ) 6 - 6 2019年5月

Cardiac Computed Tomography of Aortic Infective Endocarditis．

Harada K, Otsuka F

QJM 112 ( 5 ) 377 - 378 2019年5月

Diffuse vascular FDG uptake in late onset Takayasu arteritis．国際誌

Harada K, Hasegawa K, Otsuka F

Am. J. Med. 132 ( 5 ) e560-e561 - E561 2019年5月

Mesenteric Follicular Lymphoma．国際誌

Nishimura Y, Yamamoto A, Takahara M, Otsuka F

Clin. Case Rep. 7 ( 5 ) 1108 - 1109 2019年5月

Septic pulmonary emboli caused by infected central venous port．国際誌

Harada K, Tokumasu K, Yasuda M, Otsuka F

Postgrad. Med. J. 95 ( 1123 ) 282 - 282 2019年5月

Symptomatic Adrenal Myelolipoma．

Omura D, Nakano Y, Takase R, Otsuka F

Intern. Med 58 ( 8 ) 1181 - 1181 2019年4月

Renal intravascular lymphoma diagnosed by FDG-PET.

J. Hosp. Gen. Med. 2019年4月

Axillary lymph node tuberculosis in the elderly．

Ocho K, Tanimoto S, Shioji Y, Fujita K, Otsuka F

J. Hosp. Gen. Med. 15 106 - 107 2019年4月

FDG PET/CT findings in infected abdominal aortic aneurysm．

Harada K, Fukushima F, Tokumasu K, Hagiya H, Otsuka F

J. Hosp. Gen. Med. 1 ( 4 ) 59 - 60 2019年4月

Fever of unknown origin without increase of serum C-reactive protein in a patient with acute lymphoblastic leukemia/ lymphoblastic lymphoma．

Oka K, Fujimura T, Horiguchi S, Yano T, Kondo E, Otsuka F

J. Hosp. Gen. Med 1 ( 3 ) 45 - 49 2019年4月

Peripartum cardiomyopathy with marked pulmonary edema: A case report．

Harada K, Otsuka F

J. Hosp. Gen. Med. 1 ( 3 ) 26 - 30 2019年4月

Delayed postoperative hyponatremia after endoscopic transsphenoidal surgery for pituitary adenoma．国際誌

Tomita Y, Kurozumi K, Inagaki K, Kameda M, Ishida J, Yasuhara T, Ichikawa T, Sonoda T, Otsuka F, Date I

Acta Neurochir (Wien) 161 ( 4 ) 707 - 715 2019年4月

Effects on postgraduate-year-I residents of simulation-based learning compared to traditional lecture-style education led by postgraduate-year-II residents．国際誌

Yamamoto A, Obika M, Mandai Y, Murakami T, Miyoshi T, Ino H, Kataoka H, Otsuka F

BMC Medical Education 19 ( 1 ) 87 - 87 2019年3月

Ludwig's Angina and Mandibular Osteomyelitis after Dental Extraction.

Yuki Otsuka, Ko Harada, Yoshito Nishimura, Fumio Otsuka

JMA journal 2 ( 1 ) 87 - 88 2019年3月

Crowned Dens Syndrome Associated with hyperuricemia．

Sugihara Y, Ogawa H, Otsuka F

Intern. Med 58 ( 5 ) 765 - 765 2019年3月

Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells．国際誌

Fujisawa S, Komatsubara M, Ogura-Ochi K, Tsukamoto-Yamauchi N, Toma K, Inagaki K, Wada J, Otsuka F

Peptides 113 35 - 40 2019年3月

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice．査読国際誌

Ojima F, Saito Y, Tsuchiya Y, Ogoshi M, Fukamachi H, Inagaki K, Otsuka F, Takeuchi S , Takahashi S

Cell Tissue Res. 375 ( 3 ) 743 - 754 2019年3月

Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells．

Nagao S, Iwata N, Soejima Y, Takiguchi T, Aokage T, Kozato Y, Nakano Y, Nada T, Hasegawa T, Otsuka F

Endocr. J. 66 ( 2 ) 157 - 164 2019年2月

Diagnostic FDG PET/CT findings in Polymyalgia Rheumatica．国際誌

Otsuka Y, Harada K, Otsuka F

QJM: An International Journal of Medicine 112 ( 2 ) 139 - 140 2019年2月

Auricle pain due to tophi．

Nakano Y, Otsuka F

Intern. Med 58 ( 3 ) 453 - 453 2019年2月

Comparison of Two Electrosurgical Modes for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms: A Prospective Randomized Study．

Sugihara Y, Harada K, Oka S, Yasutomi E, Yamasaki Y, Inokuchi T, Kinugasa H, Takahara M, Hiraoka S, Otsuka F, Okada H

Acta Med. Okayama 73 ( 1 ) 81 - 84 2019年2月

A Remarkable Uptake of FDG in Huge Mediastinal Hashimoto' s Goiter．

Oka K, Hosoya T, Taira N and Otsuka F

Intern. Med 58 ( 2 ) 313 - 314 2019年1月

A Case of Juvenile Hypertension Suggestive of Adrenomedullary Hyperplasia．

Nishimura Y, Yasuda M, Hasegawa K, Otsuka F

Intern. Med 58 ( 2 ) 311 - 311 2019年1月

Hyperthyroidism with selective immunoglobulin A deficiency．

Harada K, Otsuka F

Intern. Med 58 ( 1 ) 145 - 146 2019年1月

Actinomycosis-induced trismus with orbital involvement．

Omura D, Rai K, Kusano N, Otsuka F

Intern. Med 58 ( 1 ) 153 - 154 2019年1月

Pleomorphic parotid adenoma with Graves’hyperthyroidism．

Ogura-Ochi K, Otsuka F

J. Hosp. Gen. Med. 15 26 - 27 2019年1月

A huge goiter involved in Marine-Lenhart syndrome.

Oka K, Yasuda M, Shien T and Otsuka F

J Gen Fam Med 20 ( 1 ) 37 - 38 2019年1月

Cognitive Decline due to Ectopic Primary Hyperparathyroidism 国際誌

Nishimura Y, Yamamoto A, Takahara M & Otsuka F

Clin. Case Rep 6 ( 12 ) 2513 - 2514 2018年12月

Changes in serum biochemical markers in relation to chief complaints and aging in general medicine

Omura D, Sato A, Oka K, Hanayama Y, Ogawa H, Obika M and Otsuka F

Acta Med. Okayama 72 ( 6 ) 553 - 562 2018年12月

A Case of Diffuse Esophageal Spasm Treated with Peroral Endoscopic Myotomy

Sugihara Y, Harada K, Kato R, Yamauchi K, Sakae H, Kawano S, Hiraoka S , Kawahara Y, Otsuka F, Okada H

Acta Med Okayama 72 ( 6 ) 595 - 600 2018年12月

Clival osteomyelitis with cavernous sinus thrombosis due to Fusobacterium nucleatum and Campylobacter rectus induced by tooth extraction

Oka K, Nakano Y, Sazumi Y, Michitani T, Horiguchi S, Ocho K, Iwamuro M and Otsuka F

Intern. Med 57 ( 22 ) 3325 - 3328 2018年11月

Clinical relevance of low androgen to gastroesophageal reflux symptoms

Harada K, Hanayama Y, Yasuda M, Hasegawa K, Obika M, Kataoka H, Itoshima K, Okada K and Otsuka F

Endocr. J 65 ( 10 ) 1039 - 1047 2018年10月

Photophobia in a patient with Hashimoto’s thyroiditis

Nishimura Y and Otsuka F

Intern. Med 57 ( 19 ) 2919 - 2920 2018年10月

Clinical characteristics of febrile outpatients: Possible involvement of thyroid dysfunction in febrile tachycardia

Oka K, Hanayama Y, Sato A, Omura D, Yasuda M, Hasegawa K, Obika M and Otsuka F

Acta Med. Okayama 72 ( 5 ) 447 - 456 2018年10月

The Esophagus on Sight: Ultrasonography in Achalasia.

Yoshito Nishimura, Yuusaku Sugihara, Fumio Otsuka

JMA journal 1 ( 1 ) 71 - 72 2018年9月

Effect of the interaction of metformin and bone morphogenetic proteins on ovarian steroidogenesis by human granulosa cells 国際誌

Iwata N, Hasegawa T, Fujita S, Nagao S, Nakano Y, Nada T, Nishiyama Y, Hosoya T and Otsuka F

Biochem. Biopys. Res. Commun 503 ( 3 ) 1422 - 1427 2018年9月

Enterovaginal and colovesical fistulas as late complications of pelvic radiotherapy

Iwamuro M, Hasegawa K, Hanayama Y, Kataoka H, Tanaka T, Kondo Y, Otsuka F

J. Gen. Fam. Med 19 ( 5 ) 166 - 169 2018年9月

Thyroid Follicular Carcinoma in a Teenager: A Case Report

Oka K, Shien T and Otsuka F

J. Gen. Fam. Med 19 ( 5 ) 170 - 172 2018年9月

Manifestation of central diabetes insipidus in a patient with thyroid storm

Nakamichi A, Ocho K, Oka K, Yasuda M, Hasegawa K, Iwamuro M, Obika M, Rai K and Otsuka F

Intern. Med 57 ( 13 ) 1939 - 1942 2018年7月

Interaction between orexin A and bone morphogenetic protein system on progesterone biosynthesis by rat granulosa cells 国際誌

Fujita S, Hasegawa T, Nishiyama Y, Fujisawa S, Nakano Y, Nada T, Iwata N, Kamada Y, Masuyama H and Otsuka F

J. Steroid Biochem. Mol. Biol 181 73 - 79 2018年7月

Modulation of bone morphogenetic protein activity by melatonin in ovarian steroidogenesis.

Fumio Otsuka

Reproductive medicine and biology 17 ( 3 ) 228 - 233 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Background: Melatonin regulates circadian and seasonal rhythms and the activities of hormones and cytokines that are expressed in various tissues, including the ovary, in which melatonin receptors are expressed. In the ovary, follicular growth occurs as a result of complex interactions between pituitary gonadotropins and autocrine and paracrine factors, including bone morphogenetic proteins (BMPs) that are expressed in the ovary. Methods: The effects of melatonin and BMPs on steroidogenesis were examined by using the primary cultures of rat granulosa cells. Main findings Results: It was shown that melatonin has antagonistic effects on BMP-6 actions in the granulosa cells, suggesting that melatonin is likely to contribute to balancing the biological activity of endogenous BMPs that maintain progesterone production and luteinization in the growing follicles. Similar interactions between melatonin and BMP-smad signaling also were shown in the mechanism of controlling ovarian steroidogenesis by other ligands. Conclusion: A new role of melatonin in the regulation of endocrine homeostasis in relation to BMP activity is introduced in this review.

DOI： 10.1002/rmb2.12089

Isolated follicle-stimulating hormone deficiency coincidentally diagnosed by hematospermia

Fujisawa S and Otsuka F

Intern. Med 57 ( 12 ) 1799 - 1799 2018年6月

Unilateral exophthalmos due to lymphomatous involvement

Yasuda M, M Iwamuro, Kimura K and Otsuka F

Intern. Med 57 ( 9 ) 1335 - 1335 2018年5月

RS3PE syndrome mimicking venous thrombosis

Nakano Y, Oka K, Horiguchi S and Otsuka F

J. Hosp. Gen. Med 14 ( 3 ) 223 - 224 2018年4月

Incretins modulate progesterone biosynthesis by regulating bone morphogenetic protein activity in rat granulosa cells 国際誌

Nishiyama Y,Hasegawa T, Fujita S, Iwata N, Nagao S, Hosoya T, Inagaki K, Wada Jun and Otsuka F

J. Steroid Biochem. Mol. Biol 178 82 - 88 2018年4月

Colonoscopy examination requires a longer time in patients with acromegaly than in other individuals

Iwamuro M, Yasuda M, Hasegawa K, Fujisawa S, Ogura-Ochi K, Sugihara Y, Harada K, Hiraoka S, Okada H and Otsuka F

Endocr. J 65 ( 2 ) 151 - 157 2018年2月

Far East scarlet-like fever masquerading as adult-onset Kawasaki disease

Ocho K, Iwamuro M, Hasegawa K, Hagiya H, Rai K, Yumoto T, Otsuka F

Intern. Med 57 ( 3 ) 437 - 440 2018年2月

Pneumatosis Cystoides Intestinalis

Yuusaku Sugihara, Keita Harada, Hiroko Ogawa, Fumio Otsuka, Hiroyuki Okada

Journal of Lung Health and Diseases 2018年2月

Severe Gastritis after Administration of Nivolumab and Ipilimumab

Nishimura Y, Yasuda M, Ocho K, Iwamuro M, Yamasaki O, Tanaka T, Otsuka F

Case Rep Oncol 11 ( 2 ) 549 - 556 2018年

Psoas abscess secondary to paravertebral inflammation 国際誌

Nishimura Y, Otsuka F

ID Cases 13 e00435 2018年

Interaction of Melatonin and BMP-6 in Ovarian Steroidogenesis. 国際誌

Fumio Otsuka

Vitamins and hormones 107 137 - 153 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER ACADEMIC PRESS INC

The bone morphogenetic protein (BMP) system in the ovary plays a physiological role as a luteinization inhibitor in growing follicles. BMP-6 secreted from oocytes and granulosa cells can exert an inhibitory effect on follicle-stimulating hormone (FSH) actions by suppressing adenylate cyclase activity downstream of the FSH receptor. The inhibition of FSH-induced progesterone production by BMP-6 is impaired by melatonin treatment in granulosa cells. Intracellular Smad signaling induced by BMP-6 is suppressed by melatonin, suggesting that melatonin has a regulatory role in BMP receptor signaling in granulosa cells. Since the expression of BMP-6 in granulosa cells is increased in patients with polycystic ovary syndrome, melatonin may play an important role in the maintenance of progesterone production by suppressing BMP-6 signaling, leading to the preservation of ovarian function.

DOI： 10.1016/bs.vh.2018.01.012

Diffuse Large B-cell Lymphoma Involving the Skeletal Muscle

Diffuse intestinal ganglioneuromatosis showing multiple large bowel ulcers in a patient with neurofibromatosis type 1. 査読

Iwamuro M, Omote R, Tanaka T, Sunada N, Nada T, Kondo Y, Nose S, Kawaguchi M, Otsuka F, Okada H

Intern. Med 56 ( 24 ) 3287 - 3291 2017年12月

Rapid laboratory tests for Malaria detection in Japan.

Kashihara N, Iwamuro M, Kusano N, Otsuka F

J. Gen. Fam. Med 18 ( 6 ) 470 - 471 2017年12月

Pulmonary Intravascular Lymphoma Detected by FDG-PET.

Nada T, Iwamuro M, Kimura K, Otsuka F

J. Gen. Fam. Med 18 ( 6 ) 477 - 478 2017年12月

Neck schwannoma mimicking a thyroid tumor.

Oka K, Iwamuro M, Otsuka F

J. Gen. Fam. Med 18 ( 6 ) 473 - 474 2017年12月

Hypersensitivity Pneumonitis Caused by a Home Ultrasonic Humidifier Contaminated with Candida guilliermondii.

Ando A, Hagiya H, Nada T, Kimura K, Waseda K, Rai K, Hanayama Y, Otsuka F

Intern. Med 56 ( 22 ) 3109 - 3112 2017年11月

Regulation of gonadotropins by urocortin 2 in gonadotropic tumor LβT2 cells

Kazunori Kageyama, Shingo Murasawa, Kanako Niioka, Fumio Otsuka, Hiroko Yagi, Makoto Daimon

Neuroscience Letters 660 63 - 67 2017年11月

Reply to “The Difficulty in Administering Appropriate Antimicrobial Therapy for Stenotrophomonas maltophilia Bacteremia”

Ebara H, Hagiya H, Haruki Y, Kondo E, Otsuka F

Intern. Med 56 ( 20 ) 2817 - 2817 2017年10月

Multiple abscesses caused by repetitive intramuscular injections.

Harada K, Kashihara N, Iwamuro M, Otsuka F

J. Gen. Fam. Med 18 ( 5 ) 301 - 302 2017年10月

Perimandibular abscess associated with bisphosphonate-related osteonecrosis of the jaw. 査読

Ocho K, Iwamuro M, Hagiya H, Ibaragi S, Otsuka F

J. Gen. Fam. Med 18 ( 5 ) 305 - 306 2017年10月

Clinical and hormonal characteristics of primary adrenal lymphomas: Necessity for early detection of adrenal insufficiency. 査読

Harada K, Kimura K, Iwamuro M, Terasaka T, Hanayama Y, Kondo E, Hayashi E, Yoshino T, Otsuka F

Intern. Med 56 ( 17 ) 2261 - 2269 2017年9月

A regulatory role of androgen in ovarian steroidogenesis by rat granulosa cells. 国際誌

Hasegawa T, Kamada Y, Hosoya T, Fujita S, Nishiyama Y, Iwata N, Hiramatsu Y, Otsuka F

J. Steroid Biochem. Mol. Biol 172 160 - 165 2017年9月

Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells. 査読国際誌

Ogura-Ochi K, Fujisawa S, Iwata N, Komatsubara M, Nishiyama Y, Tsukamoto-Yamauchi N, Inagaki K, Wada J, Otsuka F

Peptides 94 19 - 24 2017年8月

顕性クッシングを呈しメチラポンで加療中のAIMAHの2例

藤澤諭、稲垣兼一、西山悠紀、小松原基志、原孝行、細谷武史、当真貴志雄、越智可奈子、和田淳、大塚文男

日本内分泌学会雑誌 93 ( Suppl. Update ) 44 - 45 2017年6月

Predictors of vasovagal reactions during preoperative autologous blood donation: A single-institution analysis.

Nishimori H, Fujii N, Fujii K, Ikeda T, Asano N, Ogo H, Yamakawa M, Takagi N, Otsuka F, Ikeda K

Int. J. Hematol 105 ( 6 ) 812 - 818 2017年6月

Successful treatment with glucocorticoid for secondary Fanconi syndrome caused by sarcoidosis 査読国際誌

Omura D, Hagiya H, Hanayama Y, Hasegawa K, Morinaga H, Kikuta A, Kataoka H, Otsuka F.

Mod Rheumatol 27 ( 3 ) 545 - 547 2017年5月

A unique acromegalic osteoarthropathy: Manubriosternal joint arthritis. 国際誌

Fujisawa S, Otsuka F

Clin. Case Rep 5 ( 5 ) 725 - 726 2017年5月

Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus Infection in the Upper Gastrointestinal Tract.

Iwamuro M, Kondo E, Tanaka T, Hagiya H, Kawano S, Kawahara Y, Otsuka F, Okada H

Acta Medica Okayama 71 ( 2 ) 97 - 104 2017年4月

Idiopathic adult ileo-colonic intussusception.

Iwamuro M, Nada T, Kimura K, Hanayama Y, Otsuka F

J. Gen. Fam. Med 18 ( 2 ) 94 - 95 2017年4月

Lanthanum Deposition in the Stomach: Usefulness of Scanning Electron Microscopy for Its Detection.

Iwamuro M, Urata H, Tanaka T, Ando A, Nada T, Kimura K, Yamauchi K, Kusumoto C, Otsuka F, Okada H

Acta Medica Okayama 71 ( 1 ) 73 - 78 2017年2月

Combined effects of androgen and growth hormone on osteoblast marker expression in mouse C2C12 and MC3T3-E1 cells induced by bone morphogenetic protein. 査読国際誌

Kimura K, Terasaka T, Iwata N, Katsuyama T, Komatsubara M, Nagao R, Inagaki K, Otsuka F

J Clin Med 6 ( 1 ) 2017年1月

Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions. 査読国際誌

Komatsubara M, Hara T, Hosoya T, Toma K, Tsukamoto-Yamauchi N, Iwata N, Inagaki K, Wada J, Otsuka F

J. Steroid Biochem. Mol. Biol 165 ( Pt B ) 182 - 189 2017年1月

Ko Harada, Kosuke Kimura, Masaya Iwamuro, Fumio Otsuka

Internal Medicine 56 ( 10 ) 1269 - 1270 2017年

Clinical Characteristics of Stenotrophomonas maltophilia Bacteremia: A Regional Report and A Review of Japanese Case Series.

Ebara H, Hagiya H, Haruki Y, Kondo E, Otsuka F

Intern. Med 56 ( 2 ) 137 - 142 2017年

Hypertrophic Pachymeningitis Accompanying Scleritis

Kosuke Oka, Kazuki Ocho, Masaya Iwamuro, Fumio Otsuka

Internal Medicine 56 ( 17 ) 2383 - 2384 2017年

Paroxysmal hypertension induced by an insulinoma. 査読

Harada K, Hanayama Y, Hasegawa K, Iwamuro M, Hagiya H, Yoshida R, Otsuka F

Intern. Med. 56 ( 4 ) 413 - 417 2017年

A rare case of diffuse large B-cell lymphoma in a patient with IgG4-related autoimmune pancreatitis 査読

Yoshito Nishimura,Masaya Iwamuro*,Kazuki Ocho,Kou Hasegawa,Kosuke Kimura*,Yoshihisa Hanayama*,Eisei Kondo*,Takehiro Tanaka*,Fumio Otsuka*

Acta Medica Okayama, Acta. Medica Okayama, Acta medicinae Okayama, Acta medica Okayama 70 ( 4 ) 279 - 83 2016年8月

Increased serum KL-6 levels induced by pulmonary mycobacterium avium complex infection in a patient with RA-associated lung disease 査読

Koichi Waseda*,Kazuki Ocho,Kou Hasegawa,Kosuke Kimura*,Masaya Iwamuro*,Yoshihisa Hanayama*,Eisei Kondo*,Nobuaki Miyahara*,Fumio Otsuka*

Acta Medica Okayama, Acta. Medica Okayama, Acta medicinae Okayama, Acta medica Okayama 70 ( 3 ) 217 - 221 2016年6月

Antiobesity action of ACAM by modulating the dynamics of cell adhesion and actin polymerization in adipocytes 査読国際誌

Kazutoshi Murakami,Jun Eguchi*,Kazuyuki Hida,Atsuko Nakatsuka*,Akihiro Katayama,Miwa Sakurai,Haruki Choshi,Masumi Furutani,Daisuke Ogawa,Kohji Takei*,Fumio Otsuka*,Jun Wada*

Diabetes 65 ( 5 ) 1255 - 67 2016年5月

レボドパと酸化マグネシウムの同時内服で黒色痰・黒色尿を呈した1例査読

岩室雅也、灘隆宏、大塚文男

内科 117 ( 2 ) 2016年2月

BMP-6 modulates somatostatin effects on luteinizing hormone production by gonadrotrope cells 査読国際誌

Kishio Toma*,Fumio Otsuka*,Kohei Oguni,Tomohiro Terasaka,Motoshi Komatsubara,Naoko Tsukamoto-Yamauchi*,Kenichi Inagaki*,Hirofumi Makino

Peptides 76 96 - 101 2016年2月

Eagle症候群の1例査読

岩室雅也、小牧稔幸、大塚文男

内科 117 ( 2 ) 2016年1月

Multiple Organomegaly Exhibited in a Patient with Graves' Hyperthyroidism

Kazuki Ocho, Masaya Iwamuro, Fumio Otsuka

Internal Medicine 55 ( 18 ) 2737 - 2738 2016年

Xanthoma of the Duodenum

Masaya Iwamuro, Takehiro Tanaka, Fumio Otsuka, Hiroyuki Okada

Internal Medicine 55 ( 19 ) 2899 - 2900 2016年

Emergence of daptomycin-resistant Staphylococcus aureus during treatment 査読

Hideharu Hagiya,Yuto Haruki,Taeko Uchida,Tomoko Wada,Sumiko Shiota,Tomoharu Ishida,Hiroko Ogawa*,Tomoko Murase,Fumio Otsuka*

Internal Medicine, Japanese Journal of Medicine 55 ( 1 ) 73 - 8 2016年

White Feces Caused by the Administration of a Somatostatin Analogue. 査読

Iwamuro M, Terasaka T, Otsuka F, Okada H

Internal medicine (Tokyo, Japan) 55 ( 13 ) 1817 - 1817 2016年

Invasive Intrasellar Plasmacytoma Mimicking Pituitary Adenoma. 査読

Terasaka T, Inagaki K, Otsuka F

Internal medicine (Tokyo, Japan) 55 ( 11 ) 1501 - 1502 2016年

Reactivation of human herpes virus-6 in the renal tissue of a patient with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS) 査読

Hideharu Hagiya,Masaya Iwamuro*,Takehiro Tanaka*,Kou Hasegawa,Yoshihisa Hanayama*,Maya Kimura,Fumio Otsuka*

Internal Medicine, Japanese Journal of Medicine 55 ( 13 ) 1769 - 74 2016年

An uncommon manifestation of fitz-hugh-curtis syndrome with right-side chest pain 査読

Ko Harada,Masaya Iwamuro*,Yoshihisa Hanayama*,Fumio Otsuka*

Acta Medica Okayama, Acta. Medica Okayama, Acta medicinae Okayama, Acta medica Okayama 70 ( 2 ) 145 - 9 2016年

Detection of minute duodenal follicular lymphoma lesions using magnifying endoscopy 査読

Masaya Iwamuro*,Eisei Kondo*,Fumio Otsuka*,Katsuyoshi Takata,Tadashi Yoshino*,Yoshiro Kawahara*,Hiroyuki Okada*

Acta Medica Okayama, Acta. Medica Okayama, Acta medicinae Okayama, Acta medica Okayama 70 ( 2 ) 139 - 44 2016年

Endoscopic detection of the gastric lesions of peripheral T-cell lymphoma 査読国際誌

Masaya Iwamuro*,Kosuke Kimura*,Eisei Kondo*,Takahiro Nada,Eri Nakamura,Katsuyoshi Takata,Takehiro Tanaka*,Fumio Otsuka*,Tadashi Yoshino*,Hiroyuki Okada*

ecancermedicalscience 10 625 - 625 2016年

Hypoparathyroidism solely manifesting otological symptoms 査読

Tokiko Urabe,Hideharu Hagiya,Eri Nakamura,Fumio Otsuka*

Internal Medicine, Japanese Journal of Medicine 55 ( 2 ) 211 - 2 2016年

Pheochromocytoma Manifesting Persistent Right Shoulder Pain and Hypochondralgia 査読

Hagiya H, Nakamura E, Terasaka T, Hasegawa K, Asano K, Nada T, Kimura K, Waseda K, Hanayama Y and Otsuka F

J. General Family Med 16 ( 4 ) 292 - 296 2015年12月

Refractory chyluria due to filariasis 査読国際誌

Hagiya H, Otsuka F

Infection 43 ( 6 ) 785 - 6 2015年12月

Regulatory effects of fibroblast growth factor-8 and tumor necrosis factor-α on osteoblast marker expression induced by bone morphogenetic protein-2. 査読国際誌

Katsuyama T, Otsuka F, Terasaka T, Inagaki K, Takano-Narazaki M, Matsumoto Y, Sada KE, Makino H

Peptides 73 88 - 94 2015年11月

Superior ophthalmic vein thrombosis associated with severe facial trauma: a case report 査読国際誌

Mishima M, Yumoto T, Hashimoto H, Yasuhara T, Iida A, Tsukahara K, Sato K, Ugawa T, Otsuka F and Ujike Y

J. Med. Case Rep 9 244 - 244 2015年10月

Mutual effects of melatonin and activin on induction of aldosterone production by human adrenocortical cells. 査読国際誌

Hara T, Otsuka F, Tsukamoto-Yamauchi N, Inagaki K, Hosoya T, Nakamura E, Terasaka T, Komatsubara M, Makino H

J Steroid Biochem Mol Biol 152 8 - 15 2015年8月

A Rare Cause of Esophageal Ulcers 査読国際誌

Iwamuro M, Tsuzuki T, Otsuka F

Gastroenterology 149 ( 1 ) 31 - 2 2015年7月

Atypical onset of eosinophilic granulomatosis with polyangitis in a patient with long-term well-controlled bronchial asthma 査読

Akao S, Hagiya H, Hasegawa K, Nada T, Nakamura E, Kimura K, Waseda K, Hanayama Y, Deguchi K, Otsuka F

General Medicine 16 ( 2 ) 99 - 102 2015年6月

Gastric pseudopolyposis formed after recovery from gastric gangrene 査読国際誌

Iwamuro M, Hanayama Y, Otsuka F, Okada H.

Dig Liver Dis 47 ( 6 ) e9 - E9 2015年6月

皮疹の再燃を繰り返しCD8陽性Terminally differentiated effector memory cellの増加を認めた薬剤性過敏症症候群(DIHS)の一例

青江伯規, 今田昌秀, 高橋孝英, 榊原佳奈枝, 日野佳弥, 狩山由貴, 渡部俊幸, 岡田健, 大塚文男

日本検査血液学会雑誌 16 ( 学術集会 ) S99 - S99 2015年6月

Complication of chronic eosinophilic pneumonia in an elderly patient with Sjoegren syndrome 査読

Waseda K, Hagiya H, Hanayama Y, Terasaka T, Kimura K, Tsuzuki T, Hasegawa K, Nada T, Nakamura E, Murakami K, Kondo E, Otsuka F.

Acta Med Okayama 69 ( 2 ) 123 - 7 2015年4月

Interaction of pituitary hormones and expression of clock genes modulated by bone morphogenetic protein-4 and melatonin 査読国際誌

Tsukamoto-Yamauchi N, Terasaka T, Iwasaki Y, Otsuka F

Biochem Biophys Res Commun 459 ( 1 ) 172 - 7 2015年3月

Regulatory role of BMP-9 in steroidogenesis by rat ovarian granulosa cells 査読国際誌

Hosoya T, Otsuka F, Nakamura E, Terasaka T, Inagaki K, Tsukamoto-Yamauchi N, Hara T, Toma K, Komatsubara M, Makino H

J Steroid Biochem Mol Biol 147 85 - 91 2015年3月

Lemierre syndrome involving external jugular vein 査読国際誌

Hagiya H, Haruki Y, Otsuka F

Acute Medicine & Surgery 2 ( 1 ) 64 - 68 2015年1月

Disseminated streptococcal endophthalmitis in two diabetic patients 査読

Hagiya H, Aoki K, Tateda K, Otsuka F

Intern Med 54 ( 10 ) 1317 - 8 2015年

A paraganglioma in a hypertensive patient with unilateral renal hypoplasia 査読

Terasaka T, Hagiya H, Kimura K, Nada T, Nakamura E, Hanayama Y, Sugiyama H, Kobayashi Y, Yanai H, Otsuka F.

Acta Med Okayama 69 ( 2 ) 119 - 22 2015年

Insulinoma discovered in diffusely calcified chronic pancreatitis 査読

Terasaka T, Tsukamoto K, Inagaki K, Otsuka F

Intern Med 54 ( 21 ) 2785 - 6 2015年

Myopathy and eosinophilic pneumonia coincidentally induced by treatment with daptomycin. 査読

Hagiya H, Hasegawa K, Asano K, Terasaka T, Kimura K, Nada T, Nakamura E, Waseda K, Hanayama Y, Otsuka F

Intern Med 54 ( 5 ) 525 - 9 2015年

Hyperintense lesion in the pons in intravascular lymphoma 査読

Iwamuro M, Kimura K, Kondo E, Otsuka F

Intern Med 54 ( 18 ) 2421 - 2 2015年

Infective Internal Iliac Artery Aneurysm Caused by Campylobacter fetus 査読

Hagiya H, Ogawa H, Takahashi Y, Hasegawa K, Hanayama Y, Otsuka F.

Intern Med 54 ( 16 ) 2021 - 4 2015年

A Nephrostomy-associated urinary tract Infection caused by elizabethkingia meningoseptica 査読

Hagiya H, Ogawa H, Takahashi Y, Hasegawa K, Iwamuro M, Otsuka F.

Intern Med 54 ( 24 ) 3233 - 6 2015年

Klebsiella oxytoca producing IMP-1 detected as a first strain of carbapenem-resistant Enterobacteriacae in our hospital 査読

Hagiya H, Ogawa H, Takahashi Y, Yamamoto A, Otsuka F.

Intern Med 54 ( 22 ) 2939 - 41 2015年

Clinical ineffectiveness of latamoxef for Stenotrophomonas maltophilia infection 査読国際誌

Hagiya H, Tasaka K, Sendo T, Otsuka F

Infect Drug Resist 8 353 - 7 2015年

Actinomyces turicensis bacteremia secondary to pyometra 査読

Hagiya H, Ogawa H, Takahashi Y, Kimura K, Hasegawa K, Otsuka F.

Intern Med 54 ( 21 ) 2775 - 7 2015年

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

Hagiya H, Deguchi K, Kawada K, Otsuka F

Intern Med 54 ( 21 ) 2769 - 73 2015年

Cytomegalovirus as an Insidious Pathogen Causing Duodenitis 査読

Hagiya H, Iwamuro M, Tanaka T, Hanayama Y, Otsuka F

Acta Med Okayama 69 ( 5 ) 319 - 23 2015年

Relationships between causes of fever of unknown origin and inflammation markers: a multicenter collaborative retrospective study 査読

Naito T, Torikai K, Mizooka M, Mitsumoto F, Kanazawa K, Ohno S, Morita H, Ukimura A, Mishima N, Otsuka F, Ohyama Y, Nara N, Murakami K, Mashiba K, Akazawa K, Yamamoto K, Tanei M, Yamanouchi M, Senda S, Tazuma S, Hayashi J

Intern Med 54 ( 16 ) 1989 - 94 2015年

Tetanus in a 19-year-old Japanese Woman 査読

Hagiya H, Hirayama T, Ugawa T, Otsuka F

Intern Med 54 ( 14 ) 1825 - 1825 2015年

Relapsing Polychondritis Followed Up with FDG-PET 査読

Hagiya H, Waseda K, Otsuka F.

Intern Med 54 ( 13 ) 1675 - 6 2015年

Eagle's Syndrome Manifesting as Chronic Swallowing Pain 査読

Hagiya H, Waseda K, Ogawa H, Otsuka F

Intern Med 54 ( 10 ) 1321 - 1321 2015年

CT visualising infective vegetation. 国際誌

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Fumio Otsuka

BMJ case reports 2014 2014年12月

Gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection: a case report. 査読国際誌

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

Clinical case reports 2 ( 6 ) 286 - 95 2014年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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. 査読国際誌

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年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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年11月

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

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

Annals of vascular surgery 28 ( 8 ) 1933.e7-1933.e14 2014年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

【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

Clinical Utility of String Test as A Screening Method for Hypermucoviscosity-phenotype Klebsiella pneumonia 査読国際誌

Hagiya H, Watanabe N, Maki M, Murase T, Otsuka F

Acute Medicine & Surgery 1 ( 4 ) 245 - 246 2014年10月

Emergence of third-generation cephalosporin-resistant Enterobacteriacae at a Japanese critical care setting 査読国際誌

Hagiya H, Murase T, Suzuki M, Otsuka F, Shibayama K

Acute Medicine & Surgery 1 ( 4 ) 256 - 258 2014年10月

Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells. 査読国際誌

Nakamura E, Otsuka F, Terasaka T, Inagaki K, Hosoya T, Tsukamoto-Yamauchi N, Toma K, Makino H

J Steroid Biochem Mol Biol 143 233 - 9 2014年9月

Vasohibin-1 deficiency enhances renal fibrosis and inflammation after unilateral ureteral obstruction 査読国際誌

Watatani H, Maeshima Y, Hinamoto N, Yamasaki H, Ujike H, Tanabe K, Sugiyama H, Otsuka F, Sato Y, Makino H

Physiol Rep 2 ( 6 ) 2014年6月

Retroperitoneal bronchogenic cyst: a rare incidentaloma discovered in a juvenile hypertensive patient. 査読国際誌

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年6月

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年4月

記述言語：日本語出版者・発行元：(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年3月

記述言語：日本語出版者・発行元：(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)

Chromobacterium violaceum nosocomial pneumonia in two Japanese patients at an intensive care unit. 国際誌

Hideharu Hagiya, Tomoko Murase, Masato Suzuki, Keigo Shibayama, Yumi Kokumai, Naoto Watanabe, Miyako Maki, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 20 ( 2 ) 139 - 42 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER JAPAN KK

Chromobacterium violaceum is sensitive to temperature and the infection is usually confined to tropical or subtropical regions. Since Japan has a warm climate, C. violaceum has been scarcely isolated from clinical specimens. With global warming, however, the geographical distribution of C. violaceum infection is likely to change. We report two cases of C. violaceum nosocomial pneumonia that occurred at an intensive care center in Japan. C. violaceum was first detected from a patient in the same center as a pathogenic organism of pneumonia. Later, the organism was isolated from sputum and a ventilator circuit tube of another patient in the center. The two patients were admitted to the center in nearby beds for several days. All of the pathogens were confirmed to be C. violaceum by the nucleic acid sequence of the 16S rRNA gene and were proven to be genetically identical organisms by pulsed field gel electrophoresis. Both patients were managed with well-humidified and heated oxygen using a venturi mask and ventilator to promote excretion of sputum. It was thought that the medical respiratory care devices that provide a humid and warm environment, an optimal condition for proliferation of C. violaceum, can contribute to C. violaceum infection in a hospital environment.

DOI： 10.1016/j.jiac.2013.10.001

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

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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年1月

Lower Limb Infection in an Infant with Haemophilus influenzae Serotype b

Hideharu Hagiya, Fumio Otsuka

General Medicine 15 ( 1 ) 56 - 58 2014年

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Fumio Otsuka

Internal Medicine 53 ( 21 ) 2549 - 2550 2014年

Calcium Oxalate Crystals in the Lungs

Hideharu Hagiya, Soichiro Fushimi, Junya Itakura, Fumio Otsuka

Internal Medicine 53 ( 17 ) 2025 - 2026 2014年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読

Hideharu Hagiya, Fumio Otsuka

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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年

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

Hagiya H, Naito H, Hagioka S, Okahara S, Morimoto N, Kusano N, Otsuka F

Acta Med Okayama 68 ( 2 ) 57 - 62 2014年

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

2型糖尿病初期治療における経口糖尿病降下薬の処方選択基準に関するアルゴリズムの作成と有用性の検討査読

Rhombencephalitis caused by Listeria monocytogenes.

Hideharu Hagiya, Fumio Otsuka

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

Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study 査読国際誌

Naito T, Mizooka M, Mitsumoto F, Kanazawa K, Torikai K, Ohno S, Morita H, Ukimura A, Mishima N, Otsuka F, Ohyama Y, Nara N, Murakami K, Mashiba K, Akazawa K, Yamamoto K, Senda S, Yamanouchi M, Tazuma S, Hayashi J

BMJ Open 3 ( 12 ) e003971 - e003971 2013年12月

Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells. 査読国際誌

Terasaka T, Otsuka F, Tsukamoto N, Nakamura E, Inagaki K, Toma K, Ogura-Ochi K, Glidewell-Kenney C, Lawson MA, Makino H

Mol Cell Endocrinol 381 ( 1-2 ) 8 - 15 2013年12月

塩見明日香、三好智子、村上和敏、水島孝明、黒田真生、尾上洋、相良英憲、座間味義人、大塚文男、名倉弘哲

ライフ・サイエンスProgress in Medicine 33 ( 10 ) 2261 - 2268 2013年10月

記述言語：日本語出版者・発行元：(株)ライフ・サイエンス

薬理作用の異なる薬剤が多数処方される2型糖尿病治療域において、ガイドラインを適切に理解し薬剤の適正使用を行うことは、臨床経験の少ない研修医や新人薬剤師にとっては困難であり、煩雑な知識を要する。そこで、2型糖尿病初期治療の選択基準となるアルゴリズムを糖尿病診療ガイドラインなどに基づき作成し、その有効性について研修医、総合内科医師、薬剤師にアンケートを実施した。アルゴリズムの有用性に関する評価では、研修医と総合内科医師の間で有意差は認められなかった。一方、薬剤師では、「本アルゴリズムの使用により、医師の処方意図や患者背景について考えるきっかけとなりましたか」との質問に対して、経験年数が6年以上の薬剤師の値に比べ、経験年数が1〜5年の薬剤師の方が有意に高い値を示した。したがって、アルゴリズムを作成し治療選択基準を図式化することで、経験年数の少ない薬剤師の迅速な理解向上に寄与できることが示唆された。(著者抄録)

Rapid Progression of Graves' Ophthalmopathy Despite the Administration of Thiamazole

Melatonin receptor activation suppresses adrenocorticotropin production via BMP-4 action by pituitary AtT20 cells. 査読国際誌

Tsukamoto N, Otsuka F, Ogura-Ochi K, Inagaki K, Nakamura E, Toma K, Terasaka T, Iwasaki Y, Makino H

Mol Cell Endocrinol 375 ( 1-2 ) 1 - 9 2013年8月

Systemic varicella-zoster virus infection in two critically ill patients in an intensive care unit 査読国際誌

Hagiya H, Kimura M, Miyamoto T, Otsuka F

Virol J 10 225 - 225 2013年7月

Erdheim-Chester病が強く疑われた下垂体機能低下症の一例査読

三好智子、大塚文男、稲垣兼一、田中康司、越智可奈子、藤井一恭、藤井伸治、当真貴志雄、中村絵里、塚本尚子、武田昌也、三村由香里、小倉俊郎、景山甚郷、槇野博史

日本内分泌学会雑誌 89 ( suppl ) 21 - 23 2013年6月

GRK-6 mediates FSH action synergistically enhanced by estrogen and the oocyte in rat granulosa cells. 査読国際誌

Miyoshi T, Otsuka F, Shimasaki S

Biochemical and Biophysical Research Communications 434 ( 2 ) 401 - 6 2013年5月

Estrogen facilitates osteoblast differentiation by upregulating bone morphogenetic protein-4 signaling. 査読国際誌

Matsumoto Y, Otsuka F, Takano-Narazaki M, Katsuyama T, Nakamura E, Tsukamoto N, Inagaki K, Sada KE, Makino H

Steroids 78 ( 5 ) 513 - 20 2013年5月

中枢性尿崩症で発症したリンパ球性汎下垂体炎の1例査読

竹本玲加、大塚文男、森下美智子、森本尚孝、寺田洋明、斉藤信幸、正岡哲也、宮谷克也、田中健大

三豊総合病院雑誌 34 59 - 63 2013年4月

左眼瞼下垂を契機に診断された若年胃癌のトルコ鞍部転移の一例査読

稲垣兼一、当真貴志雄、中村絵里、越智可奈子、塚本尚子、三好智子、三村由香里、小倉俊郎、大塚文男、槇野博史

ACTH Related Peptides 24 56 - 58 2013年3月

Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis. 査読国際誌

Nakamura E, Otsuka F, Inagaki K, Tsukamoto N, Ogura-Ochi K, Miyoshi T, Toma K, Takeda M, Makino H

J Steroid Biochem Mol Biol 134 67 - 74 2013年3月

Takayuki Katsuyama, Masaya Takeda, Fumio Otsuka, Kishio Toma, Kenichi Inagaki, Ken-Ei Sada, Yukari Mimura, Toshio Ogura, Hirofumi Makino

Internal Medicine 52 ( 20 ) 2317 - 2320 2013年

Is wet swab superior to dry swab as an intranasal screening test? 査読国際誌

Hagiya H, Mio M, Murase T, Egawa K, Kokumai Y, Uchida T, Morimoto N, Otsuka F, Shiota S

J Intensive Care 1 ( 1 ) 10 - 10 2013年

Group a streptococcal meningitis in a patient with palmoplantar pustulosis 査読

Hagiya H, Otsuka F

Intern Med 52 ( 23 ) 2675 - 8 2013年

Disseminated Gonococcal Infection in An Elderly Japanese Man 査読

Hagiya H, Onishi N, Ebara H, Hanayama Y, Kokeguchi S, Nose M, Kusano N, Otsuka F

Intern Med 52 ( 23 ) 2669 - 73 2013年

Ineffectiveness of Daptomycin in the treatment of Septic Pulmonary Emboli and Persistent Bacteremia Caused by Methicillin-Resistant Staphylococcus aureus 査読

Hagiya H, Hagioka S, Otsuka F

Intern Med 52 ( 22 ) 2577 - 82 2013年

A Comprehensive Anaiysis of 1 74 Febri:e Patients Admitted to Okayama University Hospital 査読

Ryuko H, Otsuka F

Acta Med Okayama 67 ( 4 ) 227 - 37 2013年

Multifunctional bone morphogenetic protein system in endocrinology.

Fumio Otsuka

Acta medica Okayama 67 ( 2 ) 75 - 86 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

New biological activities of bone morphogenetic proteins (BMPs) in the endocrine system have recently been revealed. The BMP system is composed of approximately 30 ligands and preferential combinations of type I and type II receptors. The BMP system not only induces bone formation but also plays unique tissue-specific roles in various organs. For instance, the ovarian BMP system is a physiological inhibitor of luteinization in growing ovarian follicles. In the ovary, the expression of oocyte-derived BMP-15 is critical for female reproduction. In the pituitary, BMP-4 is a key player for initial development of the anterior pituitary, while it is also functionally involved in some differentiated pituitary tumors, including prolactinoma and Cushing's disease. In the adrenal glands, BMP-6 and BMP-4 modulate aldosterone and catecholamine production, respectively, which contributes to a functional interaction between the cortex and medulla. In the present review, recent advances in BMP biology in the field of endocrinology are described and the possibility for clinical application of BMP activity is discussed.

An in vivo role of bone morphogenetic protein-6 in aldosterone production by rat adrenal gland. 査読国際誌

Matsumoto Y, Otsuka F, Inagaki K, Tsukamoto N, Takano-Narazaki M, Miyoshi T, Nakamura E, Ogura-Ochi K, Takeda M, Makino H

J Steroid Biochem Mol Biol 132 ( 1-2 ) 8 - 14 2012年10月

Evaluation of weekly-reduction regimen of glucocorticoids in combination with cyclophosphamide for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Japanese patients. 査読国際誌

Yoshinori Matsumoto, Ken-Ei Sada, Fumio Otsuka, Mariko Takano, Noriko Toyota, Koichi Sugiyama, Hiroshi Wakabayashi, Tomoko Kawabata, Hirofumi Makino

Rheumatology international 32 ( 10 ) 2999 - 3005 2012年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER HEIDELBERG

The current therapeutic regimen recommended by the European League against Rheumatism (EULAR) for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is continuation of initially administered doses of glucocorticoids (GCs) in combination with cyclophosphamide (CYC) for 1 month followed by gradual tapering. Considering the adverse effects of GCs, another tapering regimen of GCs with CYC, which was characterized by tapering GCs weekly, was reported by the British Society of Rheumatology (weekly-reduction regimen). The aim of the present study is to evaluate the safety and efficacy of this weekly-reduction regimen for Japanese AAV patients in comparison with the monthly-reduction regimen recommended by the EULAR. We retrospectively reviewed medical records of adult patients newly diagnosed with AAV during the period from April 2000 to December 2010. The outcome measures were rates of remission, relapse, infection, and GC-induced diabetes mellitus during the first 12 months. Clinical data in the two groups and categorial variables with a possible relation to the outcomes were compared by using the t test and chi-square test, respectively. Twenty-four patients were enrolled in our study. All of the patients achieved remission, and the rates of relapse during the first 12 months were not statistically different between the two groups (P = 0.16). Patients treated with the weekly-reduction regimen were less liable to have infection (P = 0.03) and impaired glucose tolerance (P = 0.017), compared with those treated with the monthly-reduction regimen. A therapeutic strategy using the weekly-reduction regimen of GCs would be effective and would have fewer side effects than the monthly-reduction regimen.

DOI： 10.1007/s00296-011-2136-z

Pro-apoptotic effects of imatinib on PDGF-stimulated pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. 国際誌

Kazufumi Nakamura, Satoshi Akagi, Aiko Ogawa, Kengo F Kusano, Hiromi Matsubara, Daiji Miura, Soichiro Fuke, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Takahiro Oto, Ryutaro Yamanaka, Fumio Otsuka, Aya Miura, Chikao Yutani, Tohru Ohe, Hiroshi Ito

International journal of cardiology 159 ( 2 ) 100 - 6 2012年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

BACKGROUND: Remodeling of the pulmonary artery by an inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) is problematic in the treatment of idiopathic pulmonary arterial hypertension (IPAH). Effective treatment that achieves reverse remodeling is required. The aim of this study was to assess the pro-apoptotic effects of imatinib, a platelet-derived growth factor (PDGF)-receptor tyrosine kinase inhibitor, on PASMCs obtained from patients with IPAH. METHODS: PASMCs were obtained from 8 patients with IPAH undergoing lung transplantation. Cellular proliferation was assessed by (3)H-thymidine incorporation. Pro-apoptotic effects of imatinib were examined using TUNEL and caspase-3,7 assays and using transmission electron microscopy. RESULTS: Treatment with imatinib (0.1 to 10 μg/mL) significantly inhibited PDGF-BB (10 ng/mL)-induced proliferation of PASMCs from IPAH patients. Imatinib (1 μg/mL) did not induce apoptosis in quiescent IPAH-PASMCs, but it had a pro-apoptotic effect on IPAH-PASMCs stimulated with PDGF-BB. Imatinib did not induce apoptosis in normal control PASMCs with or without PDGF-BB stimulation. PDGF-BB induced phosphorylation of Akt at 15 min, and Akt phosphorylation was inhibited by imatinib in IPAH-PASMCs. Akt-I-1/2 (1 μmol/L), an Akt inhibitor, in the presence of PDGF-BB significantly increased apoptotic cells compared with the control condition. Thus, Akt-I-1/2 could mimic the effects of imatinib on PASMCs. CONCLUSION: Imatinib has anti-proliferative and pro-apoptotic effects on IPAH-PASMCs stimulated with PDGF. The inhibitory effect of imatinib on Akt phosphorylation induced by PDGF plays an important role in the pro-apoptotic effect.

DOI： 10.1016/j.ijcard.2011.02.024

Regulatory role of kit ligand-c-kit interaction and oocyte factors in steroidogenesis by rat granulose cells. 査読国際誌

Miyoshi T, Otsuka F, Nakamura E, Inagaki K, Ogura-Ochi K, Tsukamoto N, Takeda M, Makino H

Mol Cell Endocrinol 358 ( 1 ) 18 - 26 2012年7月

Bone morphogenetic protein-3b(BMP-3)inhibits osteoblast differentiation via Smad2/3 pathway by counteracting Smad1/5/8 signaling. 査読国際誌

Matsumoto Y, Otsuka F, Hino J, Miyoshi T, Takano M, Miyazato M, Makino H, Kanagawa K

Mol Cell Endocrinol 350 ( 1 ) 78 - 86 2012年3月

Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys. 査読国際誌

Suzuki J, Otsuka F, Matsumoto Y, Inagaki K, Miyoshi T, Takeda M, Tsukamoto N, Nakamura E, Ogura T, Makino H

Hypertens Res 35 ( 3 ) 312 - 7 2012年3月

BMP action in the pituitary: its possible role in modulating somatostatin sensitivity in pituitary tumor cells. 査読国際誌

Fumio Otsuka, Naoko Tsukamoto, Tomoko Miyoshi, Yasumasa Iwasaki, Hirofumi Makino

Molecular and cellular endocrinology 349 ( 2 ) 105 - 10 2012年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

The existence of a functional bone morphogenetic protein (BMP) system in the pituitary has been recognized. Recent studies have provided evidence that BMPs elicit differential actions in the regulation of prolactin (PRL) and adrenocorticotropin (ACTH) release in lactotropinoma and corticotropinoma cells, respectively. BMPs play a key role in the modulation of somatostatin receptor (SSTR) sensitivity of lactosomatotrope cells in an autocrine/paracrine manner. In addition, SSTR action enhances BMP responsiveness in corticotrope cells. The functional link between BMP receptor signaling and SSTR actions may be crucial for individual tolerance to somatostatin analogs for controlling PRL and ACTH production. Adjustment of the endogenous SSTR sensitivity may be an effective strategy to inhibit the growth activity and hormonal productivity of intractable pituitary tumors.

DOI： 10.1016/j.mce.2011.10.017

Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells. 査読国際誌

Takeda M, Otsuka F, Takahashi H, Inagaki K, Miyoshi T, Tsukamoto N, Makino H, Lawson MA

Mol Cell Endocrinol 348 ( 1 ) 147 - 54 2012年1月

Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α. 査読国際誌

Takano M, Otsuka F, Matsumoto Y, Inagaki K, Takeda M, Nakamura E, Tsukamoto N, Miyoshi T, Sada KE, Makino H

Molecular and cellular endocrinology 348 ( 1 ) 224 - 32 2012年1月

Mutual regulation of growth hormone and bone morphogenetic protein system in steroidogenesis by rat granulosa cells. 査読国際誌

Eri Nakamura, Fumio Otsuka, Kenichi Inagaki, Tomoko Miyoshi, Yoshinori Matsumoto, Kanako Ogura, Naoko Tsukamoto, Masaya Takeda, Hirofumi Makino

Endocrinology 153 ( 1 ) 469 - 80 2012年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ENDOCRINE SOC

GH induces preantral follicle growth and differentiation with oocyte maturation. However, the effects of GH on ovarian steroidogenesis and the mechanisms underlying its effects have yet to be elucidated. In this study, we investigated the actions of GH on steroidogenesis by rat granulosa cells isolated from early antral follicles by focusing on the ovarian bone morphogenetic protein (BMP) system. We found that GH suppressed FSH-induced estradiol production with reduction in aromatase expression and, in contrast, GH increased FSH-induced progesterone level with induction of steroidogenic acute regulatory protein, side chain cleavage cytochrome P450, and 3 beta-hydroxysteroid dehydrogenase. The effects of GH on steroidogenesis by granulosa cells were enhanced in the presence of the BMP antagonist noggin. Coculture of GH with oocytes did not alter GH regulation of steroidogenesis. Steroid production induced by cAMP donors was not affected by GH treatment and the GH effects on FSH-induced steroid production were not accompanied by changes in cAMP synthesis, suggesting that GH actions were not directly mediated by the cAMP-protein kinase A pathway. GH exerted synergistic effects on MAPK activation elicited by FSH, which regulated FSH-induced steroidogenesis. In addition, GH-induced signal transducer and activator of transcription phosphorylation was involved in the induction of IGF-I expression. GH increased IGF-I, IGF-I receptor, and FSH receptor expression in granulosa cells, and inhibition of IGF-I signaling restored GH stimulation of FSH-induced progesterone production, suggesting that endogenous IGF-I is functionally involved in GH effects on progesterone induction. BMP inhibited IGF-I effects that increased FSH-induced estradiol production with suppression of expression of the GH/IGF-I system, whereas GH/IGF-I actions impaired BMP-Sma and Mad related protein 1/5/8 signaling through down-regulation of the expression of BMP receptors. Thus, GH acts to modulate estrogen and progesterone production differentially through endogenous IGF-I activity in granulosa cells, in which GH-IGF-I interaction leads to antagonization of BMP actions including suppression of FSH-induced progesterone production. Mutual balance between GH/IGF-I and BMP signal intensities may be a key for regulating gonadotropin-induced steroidogenesis in growing follicles. (Endocrinology 153: 469-480, 2012)

DOI： 10.1210/en.2011-1646

Risk Factors for Infection in Patients with Remitted Rheumatic Diseases Treated with Glucocorticoids

Acta Medica Okayama 65 ( 5 ) 329 - 334 2011年10月

記述言語：英語出版者・発行元：Okayama University Medical School

It is well known that infection is one of the major causes of morbidity and mortality in rheumatic disease patients treated with high-dose glucocorticoids, especially in the early phase after achievement of disease remission. The aim of this study was to identify the risk factors for infection, with a focus on the dose of glucocorticoids administered, following the achievement of disease remission in rheumatic diseases patients. We retrospectively analyzed the medical records of rheumatic disease patients who had been treated with glucocorticoids. The primary endpoint was the incidence rate of infection during a period from 1 to 2 months after the commencement of treatment. From April 2006 to March 2010, 19 of 92 patients suffered from infection during the observation period. Age≧65 yrs, presence of interstitial pneumonia, diagnosis of systemic vasculitis and serum creatinine level≧2.0mg/dl were found to be univariate predictors for infection. However, only the presence of interstitial pneumonia was an independent risk factor for infection (HR＝4.50, 95%CI＝1.65 to 14.44) by the Cox proportional hazard model. Even after achievement of clinical remission, careful observation is needed for patients with interstitial pneumonia, more so than for those receiving high-dose glucocorticoids.

DOI： 10.18926/AMO/47015

CiNii Article

CiNii Books

Rhabdomyosarcoma discovered in the adrenal region of an elderly hypertensive patient

その他リンク： http://search.jamas.or.jp/link/ui/2012272289

Unique bioactivities of bone morphogenetic proteins in regulation of reproductive endocrine functions.

Fumio Otsuka, Kenichi Inagaki

Reproductive medicine and biology 10 ( 3 ) 131 - 142 2011年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：John Wiley and Sons Ltd

Remarkable progress has been made in understanding the mechanism by which growth factors and oocytes can regulate the development and function of granulosa cells. Insufficiency of two oocyte-specific growth factors, growth differentiation factor-9 and bone morphogenetic protein (BMP)-15, cause female infertility. Expression of mRNA and/or protein for the BMP system components, including ligands, receptors and intracellular signal transduction factors, was demonstrated in cell components of growing preantral follicles, and biofunctional experiments have further revealed many important roles of the BMP system in regulation of reproductive function. In this review, recent advances in studies on biological actions of BMPs in ovarian folliculogenesis and in related endocrine tissues are discussed. © 2011 Japan Society for Reproductive Medicine.

DOI： 10.1007/s12522-011-0082-9

Functional interaction of bone morphogenetic protein and growth hormone releasing peptide in adrenocorticotropin regulation by corticotrope cells

Naoko Tsukamoto, Fumio Otsuka, Tomoko Miyoshi, Kenichi Inagaki, Eri Nakamura, Tomohiro Terasaka, Masaya Takeda, Toshio Ogura, Yasumasa Iwasaki, Hirofumi Makino

Molecular and Cellular Endocrinology 344 ( 1-2 ) 41 - 50 2011年9月

Functional interaction of fibroblast growth factor-8, bone morphogenetic protein and estrogen receptor in breast cancer cell proliferation

Hiroko Masuda, Fumio Otsuka, Yoshinori Matsumoto, Mariko Takano, Tomoko Miyoshi, Kenichi Inagaki, Tadahiko Shien, Naruto Taira, Hirofumi Makino, Hiroyoshi Doihara

Molecular and Cellular Endocrinology 343 ( 1-2 ) 7 - 17 2011年8月

Akihiro Katayama, Fumio Otsuka, Masaya Takeda, Tomoko Miyoshi, Eri Nakamura, Kenichi Inagaki, Takehiro Tanaka, Shinya Uehara, Hirofumi Makino

Hypertension Research 34 ( 6 ) 784 - 786 2011年6月

Unexpected occurrence of adrenal Cushing’s syndrome in a patient with systemic lupus erythematosus

Akihiro Katayama, Fumio Otsuka, Katsuyuki Tanabe, Naoko Tsukamoto, Ryutaro Yamanaka, Yoshinori Matsumoto, Yasutomo Nasu, Hirofumi Makino

Hypertension Research 34 ( 5 ) 662 - 663 2011年5月

Effects of eplerenone on nephrotic syndrome in a patient with renovascular hypertension

Jiro Suzuki, Fumio Otsuka, Kenichi Inagaki, Katsuyuki Tanabe, Naoko Tsukamoto, Tomoko Miyoshi, Eri Nakamura, Toshio Ogura, Isao Kumagai, Hirofumi Makino

Hypertension Research 34 ( 3 ) 404 - 406 2011年3月

Integral role of GDF-9 and BMP-15 in ovarian function. 国際誌

Fumio Otsuka, Kirsten J McTavish, Shunichi Shimasaki

Molecular reproduction and development 78 ( 1 ) 9 - 21 2011年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

The oocyte plays an important role in regulating and promoting follicle growth, and thereby its own development, by the production of oocyte growth factors that predominantly act on supporting granulosa cells via paracrine signaling. Genetic studies in mice demonstrated critical roles of two key oocyte-derived growth factors belonging to the transforming growth factor-beta (TGF-beta) superfamily, growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15), in ovarian function. The identification of Bnip15 and Gdf9 gene mutations as the causal mechanism underlying the highly prolific or infertile nature of several sheep strains in a dosage-sensitive manner also highlighted the crucial role these two genes play in ovarian function. Similarly, large numbers of mutations in the GDF9 and BMP15 genes have been identified in women with premature ovarian failure and in mothers of dizygotic: twins. The purpose of this article is to review the genetic studies of GDF-9 and BMP-15 mutations identified in women and sheep, as well as describing the various knockout and overexpressing mouse models, and to summarize the molecular and biological functions that underlie the crucial role of these two oocyte factors in female fertility. Mol. Reprod. Dev.78: 9-21, 2011. (c) 2010 Wiley-Liss, Inc.

DOI： 10.1002/mrd.21265

Systemic Lupus Erythematosus Complicated with Acute Myocardial Infarction and Ischemic Colitis

Activities of bone morphogenetic proteins in prolactin regulation by somatostatin analogs in rat pituitary GH3 cells

Naoko Tsukamoto, Fumio Otsuka, Tomoko Miyoshi, Kenichi Inagaki, Eri Nakamura, Jiro Suzuki, Toshio Ogura, Yasumasa Iwasaki, Hirofumi Makino

Molecular and Cellular Endocrinology 332 ( 1-2 ) 163 - 169 2011年1月

Yoshinori Matsumoto, Hiroshi Wakabayashi, Fumio Otsuka, Kentaro Inoue, Mariko Takano, Ken-ei Sada, Hirofumi Makino

Internal Medicine 50 ( 21 ) 2669 - 2673 2011年

A Novel Antagonistic Effect of the Bone Morphogenetic Protein System on Prolactin Actions in Regulating Steroidogenesis by Granulosa Cells

Eri Nakamura, Fumio Otsuka, Kenichi Inagaki, Tomoko Miyoshi, Ryutaro Yamanaka, Naoko Tsukamoto, Jiro Suzuki, Toshio Ogura, Hirofumi Makino

Endocrinology 151 ( 11 ) 5506 - 5518 2010年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

To investigate the mechanism by which prolactin (PRL) regulates follicular steroidogenesis in the ovary, we examined the functional roles of PRL in steroidogenesis using rat oocyte/granulosa cell coculture and focusing on the bone morphogenetic protein (BMP) system. The expression of long and short forms of PRL receptor (PRLR) were detected in both oocytes and granulosa cells, and PRL effectively up-regulated PRLR expression in granulosa cells in the presence of FSH. PRL suppressed FSH-induced estradiol production and increased FSH-induced progesterone production in granulosa cells. The PRL effects on FSH-induced progesterone were blocked by coculture with oocytes, implying roles of oocyte-derived factors in suppression of progesterone production in PRL-exposed granulosa cells. In accordance with the data for steroids, FSH-induced aromatase expression was suppressed by PRL, whereas FSH-induced steroidogenic acute regulatory protein, P450scc (P450 side-chain cleavage enzyme), and 3β-hydroxysteroid dehydrogenase type 2 levels were amplified by PRL. However, forskolin- and N6,O2-dibutyryl cAMP-induced steroid levels and FSH- and forskolin-induced cAMP were not affected by PRL, suggesting that PRL action on FSH-induced steroidogenesis was not due to cAMP-protein kinase A regulation. Treatment with a BMP-binding protein, noggin, facilitated PRL-induced estradiol reduction, and noggin increased PRL-induced progesterone production in FSH-treated granulosa cells cocultured with oocytes, suggesting that endogenous BMPs reduce progesterone but increase estradiol when exposed to high concentrations of PRL. PRL increased the expression of BMP ligands in oocyte/granulosa cell coculture and augmented BMP-induced phosphorylated mothers against decapentaplegic 1/5/8 signaling by reducing inhibitory phosphorylated mothers against decapentaplegic 6 expression through the Janus kinase/signal transducer and activator of transcription (STAT) pathway. In addition to STAT activation, PRL enhanced FSH-induced MAPK phosphorylation in granulosa cells, in which ERK activation was preferentially involved in suppression of FSH-induced estradiol. Furthermore, noggin treatment enhanced PRLR signaling including MAPK and STAT. Considering that BMPs suppressed PRLR in granulosa cells, it is likely that the BMP system in growing follicles plays a key role in antagonizing PRLR signaling actions in the ovary exposed to high concentrations of PRL.

DOI： 10.1210/en.2010-0265

ステロイドによる骨芽細胞分化および炎症性骨分化抑制への影響

松本佳則, 大塚文男, 高野真理子, 向井知之, 武田昌也, 三好智子, 稲垣兼一, 槇野博史

日本内分泌学会雑誌 86 ( 2 ) 408 - 408 2010年9月

Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells.

Hiroyuki Otani, Fumio Otsuka, Kenichi Inagaki, Jiro Suzuki, Hirofumi Makino

Acta medica Okayama 64 ( 4 ) 213 - 8 2010年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Aldosterone production occurs in the adrenal cortex, and is regulated primarily by angiotensin II (Ang II), potassium and adrenocorticotropin (ACTH). In the presence of the aldosterone stimulators, steroidogenesis is further governed by local autocrine and/or paracrine factors in the adrenal cortex. We reported the presence of functional bone morphogenetic protein (BMP) system in the adrenal cortex and also demonstrated that BMP-6 increases Ang II-induced aldosterone production, which could be involved in the "aldosterone breakthrough" phenomenon. Aldosterone breakthrough is the phenomenon by which circulating aldosterone concentrations increase above pre-treatment levels after longterm therapy with ACE inhibitors or Ang II type 1 receptor antagonists (ARB). This phenomenon may lead to important clinical consequences since increased aldosterone in a high-salt state facilitates cardiovascular and renal damage in hypertensive patients. We found that long-term ARB treatment reverses the reduction of aldosterone synthesis by adrenocortical cells, thereby causing "cellular aldosterone breakthrough". The availability of BMP-6 in the adrenal cortex may be at least partly involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB.

DOI： 10.18926/AMO/40128

Involvement of the bone morphogenetic protein system in endothelin- and aldosterone-induced cell proliferation of pulmonary arterial smooth muscle cells isolated from human patients with pulmonary arterial hypertension

Functional relationship between fibroblast growth factor-8 and bone morphogenetic proteins in regulating steroidogenesis by rat granulosa cells

Tomoko Miyoshi, Fumio Otsuka, Misuzu Yamashita, Kenichi Inagaki, Eri Nakamura, Naoko Tsukamoto, Masaya Takeda, Jiro Suzuki, Hirofumi Makino

Molecular and Cellular Endocrinology 325 ( 1-2 ) 84 - 92 2010年8月

Estrogen and glucocorticoid regulate osteoblast differentiation through the interaction of bone morphogenetic protein-2 and tumor necrosis factor-α in C2C12 cells

Yoshinori Matsumoto, Fumio Otsuka, Mariko Takano, Tomoyuki Mukai, Ryutaro Yamanaka, Masaya Takeda, Tomoko Miyoshi, Kenichi Inagaki, Ken-ei Sada, Hirofumi Makino

Molecular and Cellular Endocrinology 325 ( 1-2 ) 118 - 127 2010年8月

Simvastatin inhibits osteoclast differentiation induced by bone morphogenetic protein-2 and RANKL through regulating MAPK, AKT and Src signaling

Misuzu Yamashita, Fumio Otsuka, Tomoyuki Mukai, Ryutaro Yamanaka, Hiroyuki Otani, Yoshinori Matsumoto, Eri Nakamura, Mariko Takano, Ken-ei Sada, Hirofumi Makino

Regulatory Peptides 162 ( 1-3 ) 99 - 108 2010年6月

Ryutaro Yamanaka, Fumio Otsuka, Kazufumi Nakamura, Misuzu Yamashita, Hiroyuki Otani, Masaya Takeda, Yoshinori Matsumoto, Kengo F Kusano, Hiroshi Ito, Hirofumi Makino

Hypertension Research 33 ( 5 ) 435 - 445 2010年5月

Effects of Bone Morphogenetic Protein (BMP) on Adrenocorticotropin Production by Pituitary Corticotrope Cells: Involvement of Up-Regulation of BMP Receptor Signaling by Somatostatin Analogs

Naoko Tsukamoto, Fumio Otsuka, Tomoko Miyoshi, Ryutaro Yamanaka, Kenichi Inagaki, Misuzu Yamashita, Hiroyuki Otani, Masaya Takeda, Jiro Suzuki, Toshio Ogura, Yasumasa Iwasaki, Hirofumi Makino

Endocrinology 151 ( 3 ) 1129 - 1141 2010年3月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

The mechanism by which somatostatin analogs suppress ACTH production by corticotropinomas has yet to be fully elucidated. We here studied the effects of somatostatin analogs on ACTH secretion using mouse corticotrope AtT20 cells focusing on the biological activity of bone morphogenetic proteins (BMPs). BMP ligands, receptors and Smads, and somatostatin receptors (SSTRs)-2, -3, and -5 were expressed in AtT20 cells. BMP-2, -4, -6, and -7 decreased basal ACTH production with BMP-4 effects being the most prominent. BMP-4 also inhibited CRH-induced ACTH production and proopiomelanocortin (POMC) transcription. However, the decrease in CRH-induced cAMP accumulation caused by BMP-4 was not sufficient to completely account for BMP-4 actions, indicating that ACTH suppression by BMPs was not directly linked to cAMP inhibition. CRH-activated ERK1/ERK2, p38-MAPK, stress-activated protein kinase/c-Jun NH2-terminal kinase, protein kinase C, and Akt pathways and CRH-induced ACTH synthesis was significantly decreased in the presence of U0126 or SB203580. Because BMPs attenuated CRH-induced ERK and p38 phosphorylation, it was suggested that BMP-4 suppresses ACTH production by inhibiting CRH-induced ERK and p38 phosphorylation. Somatostatin analogs octreotide and pasireotide (SOM230) significantly suppressed CRH-induced ACTH and cAMP production in AtT20 cells and reduced ERK and p38 phosphorylation. Notably, CRH-induced ACTH production was enhanced in the presence of noggin, a BMP-binding protein. The inhibitory effects of octreotide and SOM230 on CRH-induced ACTH production were also attenuated by noggin, implying that the endogenous BMP system plays a key role in inhibiting CRH-induced ACTH production by AtT20 cells. The findings that OCT and SOM230 up-regulated BMP-Smad1/Smad5/Smad8 signaling and ALK-3 and BMPRII and down-regulated inhibitory Smad6/7 establish that the activation of endogenous BMP system is functionally involved in the mechanism by which somatostatin analogs suppress CRH-induced ACTH production.

DOI： 10.1210/en.2009-1102

Inhibitory Effects of Simvastatin on Platelet-derived Growth Factor Signaling in Pulmonary Artery Smooth Muscle Cells From Patients With Idiopathic Pulmonary Arterial Hypertension

骨軟骨と滑膜 BMPによる骨芽細胞分化に対するTNF-αおよびsteroidの作用機序の検討

松本佳則, 大塚文男, 向井知之, 高野真理子, 山中龍太郎, 山下美鈴, 塚本尚子, 佐田憲映, 槇野博史

日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 54回・19回 526 - 526 2010年3月

Multiple endocrine regulation by bone morphogenetic protein system.

Fumio Otsuka

Endocrine journal 57 ( 1 ) 3 - 14 2010年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN ENDOCRINE SOC

Bone morphogenetic proteins (BMPs) were originally identified with regard to their actions to regulate ectopic formation of bone and cartilage and early embryonic development. Subsequently, our research program has investigated a BMP system that exists in the mammalian ovary and plays roles in regulating numerous granulosa cell functions. BMP ligands including BMP-2, 4, -6, -7 and -15 were found to inhibit gondotropin-dependent progesterone synthesis by granulosa cells, which led to the hypothesis that BMPs are a physiological luteinization inhibitor in growing ovarian follicles during the follicular phase of the ovarian cycle. The physiological importance of the BMP system for normal mammalian reproduction has been further recognized by the discovery of aberrant reproductive phenotypes of female sheep and humans having mutated genes encoding BMP-15. Physiological roles of BMPs in the pituitary, hypothalamus, adrenal and other tissues have also been discovered. Here we discuss recent advances in the understanding of autocrine/paracrine actions of BMPs in the systemic regulation of endocrine function.

DOI： 10.1507/endocrj.K09E-310

Tetsuya Ikeda, Kazufumi Nakamura, Satoshi Akagi, Kengo Fukushima Kusano, Hiromi Matsubara, Hideki Fujio, Aiko Ogawa, Aya Miura, Daiji Miura, Takahiro Oto, Ryutaro Yamanaka, Fumio Otsuka, Hiroshi Date, Tohru Ohe, Hiroshi Ito

Journal of Cardiovascular Pharmacology 55 ( 1 ) 39 - 48 2010年1月

Regulation of GNRH production by estrogen and bone morphogenetic proteins in GT1-7 hypothalamic cells

Hiroyuki Otani, Fumio Otsuka, Masaya Takeda, Tomoyuki Mukai, Tomohiro Terasaka, Tomoko Miyoshi, Kenichi Inagaki, Jiro Suzuki, Toshio Ogura, Mark A Lawson, Hirofumi Makino

Journal of Endocrinology 203 ( 1 ) 87 - 97 2009年10月

掲載種別：研究論文（学術雑誌）出版者・発行元：Bioscientifica

Recent studies have shown that bone morphogenetic proteins (BMPs) are important regulators in the pituitary–gonadal endocrine axis. We here investigated the effects of BMPs on GNRH production controlled by estrogen using murine GT1-7 hypothalamic neuron cells. GT1-7 cells expressed estrogen receptor α (ERα; ESR1 as listed in MGI Database), ERβ (ESR2 as listed in MGI Database), BMP receptors, SMADs, and a binding protein follistatin. Treatment with BMP2 and BMP4 had no effect on Gnrh mRNA expression; however, BMP6 and BMP7 significantly increased Gnrh mRNA expression as well as GnRH production by GT1-7 cells. Notably, the reduction of Gnrh expression caused by estradiol (E₂) was restored by cotreatment with BMP2 and BMP4, whereas it was not affected by BMP6 or BMP7. E₂ activated extracellular signal-regulated kinase (ERK) 1/2 and stress-activated protein kinase/c-Jun NH₂-terminal kinase (SAPK/JNK) signaling but did not activate p38-mitogen-activated protein kinase (MAPK) signaling in GT1-7 cells. Inhibition of ERK1/ERK2 reversed the inhibitory effect of estrogen on Gnrh expression, whereas SAPK/JNK inhibition did not affect the E₂ actions. Expression levels of Erα and Erβ were reduced by BMP2 and BMP4, but were increased by BMP6 and BMP7. Treatment with an ER antagonist inhibited the E₂ effects on Gnrh suppression including reduction of E₂-induced ERK phosphorylation, suggesting the involvement of genomic ER actions in Gnrh suppression. BMP2 and BMP4 also suppressed estrogen-induced phosphorylation of ERK1/ERK2 and SAPK/JNK signaling, suggesting that BMP2 and BMP4 downregulate estrogen effects by attenuating ER–MAPK signaling. Considering that BMP6 and BMP7 increased the expression of α1E-subunit of R-type calcium channel (Cacna1e), which is critical for GNRH secretion, it is possible that BMP6 and BMP7 directly stimulate GNRH release by GT1-7 cells. Collectively, a newly uncovered interaction of BMPs and ER may be involved in controlling hypothalamic GNRH production and secretion via an autocrine/paracrine mechanism.

DOI： 10.1677/joe-09-0065

p38-Mitogen-Activated Protein Kinase Stimulated Steroidogenesis in Granulosa Cell-Oocyte Cocultures: Role of Bone Morphogenetic Proteins 2 and 4

Kenichi Inagaki, Fumio Otsuka, Tomoko Miyoshi, Misuzu Yamashita, Mina Takahashi, Junko Goto, Jiro Suzuki, Hirofumi Makino

Endocrinology 150 ( 4 ) 1921 - 1930 2009年4月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

Roles of the p38-MAPK pathway in steroidogenesis were investigated using coculture of rat granulosa cells with oocytes. Activin and FSH readily phosphorylated p38 in granulosa cells. Activin effect on p38 phosphorylation was abolished by a selective activin receptor-like kinase-4, -5, and -7 inhibitor, SB431542. SB431542 decreased FSH-induced estradiol but had no effect on progesterone production with a marginal cAMP reduction, suggesting that endogenous activin is primarily involved in estradiol synthesis. FSH-induced p38 activation was not affected either by SB431542 or follistatin, suggesting that FSH activates p38 not through the endogenous activin. Bone morphogenetic protein (BMP)-2 and BMP-4 also enhanced FSH-induced p38 phosphorylation, which was augmented by oocyte action. A specific p38 inhibitor, SB203580, decreased FSH-induced estradiol production. However, FSH-induced cAMP accumulation was not changed by SB203580, suggesting that p38 activation is linked to estradiol synthesis independently of cAMP. BMP-2 and BMP-4 inhibited FSH- and forskolin (FSK)-induced progesterone and cAMP synthesis regardless of oocyte action. BMP-2, BMP-4, and activin increased FSH-induced estradiol production, which was enhanced in the presence of oocytes. In contrast to activin that enhanced FSK-induced estradiol, BMP-2 and BMP-4 had no effects on FSK-induced estradiol production, suggesting that BMP-2 and BMP-4 directly activate FSH-receptor signaling. Given that activin increased, but BMP-2 and BMP-4 decreased, FSH-induced cAMP, the effects of BMP-2 and BMP-4 on estradiol enhancement appeared to be diverged from the cAMP-protein kinase A pathway. Thus, BMP-2 and BMP-4 differentially regulate steroidogenesis by stimulating FSH-induced p38 and suppressing cAMP. The former is involved in estradiol production and enhanced by oocyte action, whereas the latter leads to reduction of progesterone synthesis.

DOI： 10.1210/en.2008-0851

Enhancement of aldosterone-induced catecholamine production by bone morphogenetic protein-4 through activating Rho and SAPK/JNK pathway in adrenomedullar cells

Junko Goto, Fumio Otsuka, Misuzu Yamashita, Jiro Suzuki, Hiroyuki Otani, Hiroko Takahashi, Tomoko Miyoshi, Yukari Mimura, Toshio Ogura, Hirofumi Makino

American Journal of Physiology-Endocrinology and Metabolism 296 ( 4 ) E904 - E916 2009年4月

掲載種別：研究論文（学術雑誌）出版者・発行元：American Physiological Society

Here we investigated the effects of mineralocorticoid in the regulation of catecholamine biosynthesis using rat pheochromocytoma PC12 cells. Expression of mineralocorticoid receptor (MR) was confirmed in undifferentiated PC12 cells. Aldosterone stimulated dopamine production by PC12 cells without any increase in cAMP activity. Aldosterone-induced dopamine accumulation was enhanced in accordance with the increase in the rate-limiting enzyme tyrosine hydroxylase (TH). Blocking MR with eplerenone suppressed aldosterone-induced increases of TH mRNA and dopamine production. A glucocorticoid receptor (GR) antagonist, RU-486, attenuated dexamethasone- but not aldosterone-induced TH expression. Cycloheximide reduced both aldosterone- and dexamethasone-induced TH mRNA. A SAPK/JNK inhibitor, SP600125, suppressed aldosterone-induced TH mRNA expression; however, the aldosterone-induced TH expression was not affected by inhibition of ERK1/2, p38-MAPK, Rho-kinase, PI 3-kinase, and PKC. It was of note that cotreatment with eplerenone and SP600125 restored aldosterone-induced TH mRNA expression to basal levels. To investigate the involvement of bone morphogenetic protein (BMP) actions in aldosterone-induced catecholamine production, we examined the effects of BMP-4 and BMP-7, which are expressed in the adrenal medulla, on catecholamine biosynthesis. BMP-4 preferentially enhanced aldosterone-induced TH mRNA and dopamine production, although BMP-4 alone did not affect TH expression. The BMP-4 enhancement of aldosterone-induced TH expression was not observed in cells treated with eplerenone. BMP-4 did not affect MR expression of PC12 cells; however, it did enhance aldosterone-induced SAPK/JNK phosphorylation. Inhibition of SAPK/JNK or Rho suppressed BMP-4 enhancement of aldosterone-induced TH expression. Collectively, our findings demonstrate that aldosterone stimulates catecholamine biosynthesis in adrenomedullar cells via MR through genomic action and partly through nongenomic action by Rho-SAPK/JNK signaling, the latter of which is facilitated by BMP-4. A functional link between MR actions and endogenous BMP may be involved in the catecholamine production.

DOI： 10.1152/ajpendo.90840.2008

Adrenal ganglioneuroma accompanying catecholamine-producing adrenocortical cells

骨粗鬆症破骨細胞活性化に対するBMP-2の影響とsimvastatinの作用機序の検討

山下美鈴, 大塚文男, 向井知之, 山中龍太郎, 矢野隆介, 山村昌弘, 槇野博史

日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 53回・18回 283 - 283 2009年3月

J. Goto, F. Otsuka, M. Omori, H. Makino

Journal of Endocrinological Investigation 32 ( 2 ) 192 - 192 2009年2月

Effects of Growth Hormone Reduction in a Patient with Polycystic Ovary Syndrome Complicated with Acromegaly

Junko GOTO, Fumio OTSUKA, Kenichi INAGAKI, Naoko TSUKAMOTO, Jiro SUZUKI, Tomoko MIYOSHI, Toshio OGURA, Yasuhiko KAMADA, Hirofumi MAKINO

Endocrine Journal 56 ( 1 ) 157 - 160 2009年

Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation

Mina Takahashi, Fumio Otsuka, Tomoko Miyoshi, Hiroyuki Otani, Junko Goto, Misuzu Yamashita, Toshio Ogura, Hirofumi Makino, Hiroyoshi Doihara

Journal of Endocrinology 199 ( 3 ) 445 - 455 2008年12月

掲載種別：研究論文（学術雑誌）出版者・発行元：Bioscientifica

Estrogen is involved in the development and progression of breast cancer. Here, we investigated the effects of bone morphogenetic proteins (BMPs) on breast cancer cell proliferation caused by estrogen using human breast cancer MCF-7 cells. MCF-7 cells express estrogen receptors (ESR1 and ESR2), BMP receptors, and SMAD signaling molecules. Estradiol and membrane-impermeable estradiol stimulated MCF-7 cell proliferation. Estradiol also reduced mRNA levels of ESR1, aromatase, and steroid sulfatase. Treatment with BMPs and activin had no effects on MCF-7 cell proliferation. However, BMP2, BMP4, BMP6, BMP7, and activin suppressed estradiol-induced cell mitosis, with the effects of BMP6, BMP7, and activin being more prominent than those of BMP2 and BMP4. Activin decreased ESR1 mRNA expression, while BMP6 and BMP7 impaired steroid sulfatase expression in MCF-7 cells. Interestingly, SMAD1,5,8 activation elicited by BMP6 and BMP7, but not by BMP2 and BMP4, was preserved even under the exposure of a high concentration of estradiol. The difference of BMP responsiveness was likely due to the differential modulation of BMP receptor expression induced by estradiol. In this regard, estradiol decreased the expression levels of BMPR1A, BMPR1B, ACVR2A, and ACVR2B but did not affect ACVR1 and BMPRII, leading to the sustained effects of BMP6 and BMP7 in estrogen-treated MCF-7 cells. Estradiol rapidly activated MAPK phosphorylation including extracellular signal-regulated kinase 1/2, p38, and stress-activated protein kinase/c-Jun NH2-terminal kinase pathways and BMP6, BMP7, and activin preferentially inhibited estradiol-induced p38 phosphorylation. SB203580, a selective p38 MAPK inhibitor effectively suppressed estradiol-induced cell mitosis, suggesting that p38 MAPK plays a key role in estrogen-sensitive breast cancer cell proliferation. Thus, a novel interrelationship between estrogen and the breast cancer BMP system was uncovered, in which inhibitory effects of BMP6 and BMP7 on p38 signaling and steroid sulfatase expression were functionally involved in the suppression of estrogen-induced mitosis of breast cancer cells.

DOI： 10.1677/joe-08-0226

肺動脈性肺高血圧症とBMPシステム異常 (特集肺動脈性肺高血圧症--基礎研究と臨床の進歩) -- (発症に関する最新研究動向)

大塚文男

日本臨床 66 ( 11 ) 2083 - 90 2008年11月

Aldosterone Breakthrough Caused by Chronic Blockage of Angiotensin II Type 1 Receptors in Human Adrenocortical Cells: Possible Involvement of Bone Morphogenetic Protein-6 Actions

Hiroyuki Otani, Fumio Otsuka, Kenichi Inagaki, Jiro Suzuki, Tomoko Miyoshi, Yoshihiro Kano, Junko Goto, Toshio Ogura, Hirofumi Makino

Endocrinology 149 ( 6 ) 2816 - 2825 2008年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

Circulating aldosterone concentrations occasionally increase after initial suppression with angiotensin II (Ang II) converting enzyme inhibitors or Ang II type 1 receptor blockers (ARBs), a phenomenon referred to as aldosterone breakthrough. However, the underlying mechanism causing the aldosterone breakthrough remains unknown. Here we investigated whether aldosterone breakthrough occurs in human adrenocortical H295R cells in vitro. We recently reported that bone morphogenetic protein (BMP)-6, which is expressed in adrenocortical cells, enhances Ang II- but not potassium-induced aldosterone production in human adrenocortical cells. Accordingly, we examined the roles of BMP-6 in aldosterone breakthrough induced by long-term treatment with ARB. Ang II stimulated aldosterone production by adrenocortical cells. This Ang II stimulation was blocked by an ARB, candesartan. Interestingly, the candesartan effects on Ang II-induced aldosterone synthesis and CYP11B2 expression were attenuated in a course of candesartan treatment for 15 d. The impairment of candesartan effects on Ang II-induced aldosterone production was also observed in Ang II- or candesartan-pretreated cells. Levels of Ang II type 1 receptor mRNA were not changed by chronic candesartan treatment. However, BMP-6 enhancement of Ang II-induced ERK1/2 signaling was resistant to candesartan. The BMP-6-induced Smad1, -5, and -8 phosphorylation, and BRE-Luc activity was augmented in the presence of Ang II and candesartan in the chronic phase. Chronic Ang II exposure decreased cellular expression levels of BMP-6 and its receptors activin receptor-like kinase-2 and activin type II receptor mRNAs. Cotreatment with candesartan reversed the inhibitory effects of Ang II on the expression levels of these mRNAs. The breakthrough phenomenon was attenuated by neutralization of endogenous BMP-6 and activin receptor-like kinase-2. Collectively, these data suggest that changes in BMP-6 availability and response may be involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB.

DOI： 10.1210/en.2007-1476

Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells

Tomoko Miyoshi, Fumio Otsuka, Hiroyuki Otani, Kenichi Inagaki, Junko Goto, Misuzu Yamashita, Toshio Ogura, Yasumasa Iwasaki, Hirofumi Makino

Journal of Endocrinology 197 ( 1 ) 159 - 169 2008年4月

掲載種別：研究論文（学術雑誌）出版者・発行元：Bioscientifica

Here we investigated roles of the pituitary bone morphogenetic protein (BMP) system in modulating GH production regulated by a somatostatin analog, octreotide (OCT) and a dopamine agonist, bromocriptine (BRC) in rat pituitary somatolactotrope tumor GH3 cells. The GH3 cells were found to express BMP ligands, including BMP-4 and BMP-6; BMP type-1 and type-2 receptors (except the type-1 receptor, activin receptor-like kinase (ALK)-6); and Smad signaling molecules. Forskolin stimulated GH production in accordance with cAMP synthesis. BRC, but not OCT, suppressed forskolin-induced cAMP synthesis by GH3 cells. Individual treatment with OCT and BRC reduced forskolin-induced GH secretion. A low concentration (0.1 μM) of OCT in combination with BRC (1–100 μM) exhibited additive effects on reducing GH and cAMP production induced by forskolin. However, a high concentration (10 μM) of OCT in combination with BRC failed to suppress GH and cAMP production. BMP-4 specifically enhanced GH secretion and cAMP production induced by forskolin in GH3 cells. BRC, but not OCT, inhibited BMP-4-induced activation of Smad1,5,8 phosphorylation and Id-1 transcription and decreased ALK-3 expression. Of note, in the presence of a high concentration of OCT, the BRC effects suppressing BMP-4-Smad1,5,8 signaling were significantly impaired. In the presence of BMP-4, a high concentration of OCT also attenuated the BRC effects suppressing forskolin-induced GH and cAMP production. Collectively, a high concentration of OCT interferes with BRC effects by reducing cAMP production and suppressing BMP-4 signaling in GH3 cells. These findings may explain the mechanism of resistance of GH reduction to a combination therapy with OCT and BRC for GH-producing pituitary adenomas.

DOI： 10.1677/joe-07-0549

Simvastatin antagonizes tumor necrosis factor-α inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway

TNF-αによる骨芽細胞分化の抑制に対するSimvastatin作用の検討

山下美鈴, 大塚文男, 向井知之, 相田哲史, 山村昌弘, 槇野博史

日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 52回・17回 247 - 247 2008年4月

Misuzu Yamashita, Fumio Otsuka, Tomoyuki Mukai, Hiroyuki Otani, Kenichi Inagaki, Tomoko Miyoshi, Junko Goto, Masahiro Yamamura, Hirofumi Makino

Journal of Endocrinology 196 ( 3 ) 601 - 613 2008年3月

掲載種別：研究論文（学術雑誌）出版者・発行元：Bioscientifica

Recent studies have shown that the mevalonate pathway plays an important role in skeletal metabolism. Statins stimulate bone morphogenetic proteins-2 (BMP-2) production in osteoblasts, implicating a possible beneficial role for statins in promoting anabolic effects on bone. Here, we investigated the effects of a lipophilic simvastatin on osteoblast differentiation using mouse myoblast C2C12 cells, in the presence of tumor necrosis factor-α (TNF-α), an inflammatory cytokine that inhibits osteogenesis. The addition of TNF-α to C2C12 cells suppressed the BMP-2-induced expression of key osteoblastic markers including Runx2 and alkaline phosphatase (ALP) activity. Simvastatin had no independent effects on Runx2 and alkaline phosphatase activity; however, it reversed the suppressive effects of TNF-α. The ability of simvastatin to reverse TNF-α inhibition of BMP-induced Smad1,5,8 phosphorylation and Id-1 promoter activity suggests the involvement of Smad signaling pathway in simvastatin action. In addition, cDNA array analysis revealed that simvastatin increased expression levels of Smads in C2C12 cells exposed to TNF-α that also activated mitogen-activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), P38, and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Simvastatin potently suppressed TNF-α-induced phosphorylation of ERK1/2 and SAPK/JNK by inhibiting TNF-α-induced membrane localization of Ras and RhoA. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) reversed the simvastatin effects on TNF-α-induced activation of Ras/Rho/MAPK pathways. FPP and GGPP also restored the simvastatin effects on TNF-α-induced suppression of Runx2 and ALP activity. In addition, simvastatin decreased the expression levels of TNF type-1 and -2 receptor mRNAs. Collectively, simvastatin supports BMP-induced osteoblast differentiation through antagonizing TNF-α-to-Ras/Rho/MAPK pathway and augmenting BMP-Smad signaling, suggesting a potential usage of statins to ameliorate inflammatory bone damage.

DOI： 10.1677/joe-07-0532

A Rare Tumor in the Adrenal Region: Neuron-specific Enolase (NSE)-Producing Leiomyosarcoma in an Elderly Hypertensive Patient

その他リンク： https://joe.bioscientifica.com/downloadpdf/journals/joe/196/3/601.xml

Junko GOTO, Fumio OTSUKA, Ryo KODERA, Tomoko MIYOSHI, Masaru KINOMURA, Hiroyuki OTANI, Yukari MIMURA, Toshio OGURA, Hiroyuki YANAI, Yasutomo NASU, Hirofumi MAKINO

Endocrine Journal 55 ( 1 ) 175 - 181 2008年

Effects of peroxisome proliferator-activated receptor activation on gonadotropin transcription and cell mitosis induced by bone morphogenetic proteins in mouse gonadotrope LβT2 cells

Masaya Takeda, Fumio Otsuka, Hiroyuki Otani, Kenichi Inagaki, Tomoko Miyoshi, Jiro Suzuki, Yukari Mimura, Toshio Ogura, Hirofumi Makino

Journal of Endocrinology 194 ( 1 ) 87 - 99 2007年7月

掲載種別：研究論文（学術雑誌）出版者・発行元：Bioscientifica

Involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ ) activation and bone morphogenetic protein (BMP) signaling in regulating cell proliferation and hormonal production of pituitary tumors has been reported, although the underlying mechanism remains poorly understood. Here, we investigated regulatory roles of PPARα and PPARγ in gonadotropin transcription and cell mitosis modulated by pituitary activin/BMP systems using a mouse gonadotropinoma cell line Lβ T2, which expresses activin/BMP receptors, transcription factor Smads, PPARα , and PPARγ . In Lβ T2 cells, BMP signaling shown by Smad1/5/8 phosphorylation and Id-1 transcription was readily activated by BMPs. A PPARγ agonist, pioglitazone significantly reduced BMP-induced DNA synthesis by Lβ T2; whereas the PPARα agonist, fenofibric acid, did not. In accordance with the effects on cell mitosis, pioglitazone but not fenofibric acid significantly decreased BMP-induced Id-1-Luc activation. Neither fenofibric acid nor pioglitazone affected activin signaling detected by (CAGA)⁹-Luc activity. Both PPARα and PPARγ ligands directly suppressed transcriptional activities of FSHβ , LHβ , and GnRHR. Activation of PPARα and PPARγ increased mRNA levels of follistatin, but did not affect the expression of follistatin-related gene. Thus, PPAR agonists not only directly suppress gonadotropin transcription and BMP signaling, but also inhibit the biological actions of activins which facilitate gonadotropin transcription through upregulating follistatin expression. In addition, pioglitazone increased BMP ligands mRNA, but decreased activin-β B mRNA in Lβ T2 cells. Collectively, PPAR activation differentially regulates gonadotrope cell proliferation and gonadotropin transcription in a ligand-dependent manner.

DOI： 10.1677/joe-07-0138

Antagonistic effects of bone morphogenetic protein-4 and -7 on renal mesangial cell proliferation induced by aldosterone through MAPK activation

その他リンク： https://joe.bioscientifica.com/downloadpdf/journals/joe/194/1/1940087.xml

TNF-α inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling

Tomoyuki Mukai, Fumio Otsuka, Hiroyuki Otani, Misuzu Yamashita, Koji Takasugi, Kenichi Inagaki, Masahiro Yamamura, Hirofumi Makino

Biochemical and Biophysical Research Communications 356 ( 4 ) 1004 - 1010 2007年5月

Hiroyuki Otani, Fumio Otsuka, Kenichi Inagaki, Masaya Takeda, Tomoko Miyoshi, Jiro Suzuki, Tomoyuki Mukai, Toshio Ogura, Hirofumi Makino

American Journal of Physiology-Renal Physiology 292 ( 5 ) F1513 - F1525 2007年5月

掲載種別：研究論文（学術雑誌）出版者・発行元：American Physiological Society

Aldosterone and angiotensin II (ANG II) contribute to the development and progression of renal damage. Here we investigated the effects of bone morphogenetic proteins (BMPs) on renal cell proliferation evoked by aldosterone and ANG II with mouse mesangial cells, which express mineralocorticoid receptors (MR), ANG II type 1 receptors, and BMP signaling molecules. Aldosterone and ANG II stimulated mesangial cell mitosis and activated ERK1/2 and SAPK/JNK signaling. These aldosterone effects were neutralized by the MR antagonist eplerenone and inhibition of transcription or translation, suggesting the involvement of genomic activation via MR. BMP-4 and BMP-7 stimulated Smad1, -5, -8 signaling more potently than BMP-2 and BMP-6, leading to suppression of mesangial cell mitosis and MR expression. MAPK inhibitors including U-0126 and SP-600125, but not SB-203580, suppressed aldosterone-induced cellular DNA synthesis, implying that ERK1/2 and SAPK/JNK pathways play crucial roles in mesangial cell proliferation. BMP-4 and BMP-7 inhibited phosphorylation of ERK1/2 and SAPK/JNK induced by aldosterone while activating p38 pathway, resulting in inhibition of aldosterone-induced cell mitosis. In contrast, aldosterone modulated the mesangial BMP system by decreasing expression of ALK-3, BMP-4, and BMP-7 while increasing inhibitory Smad6 expression. Thus novel functional cross talk between the mesangial BMP system and aldosterone signaling was uncovered, in which inhibition of MAPK signaling and MR expression by BMP-4 and BMP-7 may be involved in ameliorating renal damage due to mesangial proliferation caused by aldosterone.

DOI： 10.1152/ajprenal.00402.2006

骨形成蛋白(BMP)により誘導される骨芽細胞分化に対する炎症性サイトカインTNF-αの抑制作用

バセドウ病ともやもや病を合併し経過中に脳梗塞を発症した1型糖尿病の1例

更井啓, 四方賢一, 大森一慶, 佐藤千景, 西下伸吾, 和田淳, 鈴木二郎, 大塚文男, 槇野博史, 山本久美子, 佐々原渉

糖尿病 50 ( 5 ) 356 - 356 2007年5月

大塚文男, 向井知之, 大谷寛之, 稲垣兼一, 三好智子, 後藤順子, 鈴木二郎, 三村由香里, 小倉俊郎, 槇野博史

日本内分泌学会雑誌 83 ( 1 ) 155 - 155 2007年4月

BMPによる骨芽細胞の分化に及ぼすTNF-αの作用メカニズムの検討

向井知之, 大塚文男, 山下美鈴, 高杉幸司, 相田哲史, 槇野博史, 山村昌弘

日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 51回・16回 365 - 365 2007年4月

Regulatory expression of bone morphogenetic protein-6 system in aldosterone production by human adrenocortical cells

Kenichi Inagaki, Fumio Otsuka, Jiro Suzuki, Hiroyuki Otani, Masaya Takeda, Yoshihiro Kano, Tomoko Miyoshi, Misuzu Yamashita, Toshio Ogura, Hirofumi Makino

Regulatory Peptides 138 ( 2-3 ) 133 - 140 2007年2月

Differential Regulation of Steroidogenesis by Bone Morphogenetic Proteins in Granulosa Cells: Involvement of Extracellularly Regulated Kinase Signaling and Oocyte Actions in Follicle-Stimulating Hormone-Induced Estrogen Production

Tomoko Miyoshi, Fumio Otsuka, Kenichi Inagaki, Hiroyuki Otani, Masaya Takeda, Jiro Suzuki, Junko Goto, Toshio Ogura, Hirofumi Makino

Endocrinology 148 ( 1 ) 337 - 345 2007年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

In the present study, we investigated the cellular mechanism by which oocytes and bone morphogenetic proteins (BMPs) govern FSH-induced steroidogenesis using rat primary granulosa cells. BMP-6 and BMP-7 both inhibited FSH- and forskolin (FSK)-induced progesterone synthesis and reduced cAMP synthesis independent of the presence or absence of oocytes. BMP-7 also increased FSH-induced estradiol production, and the response was further augmented in the presence of oocytes. In contrast, BMP-6 had no impact on estradiol synthesis regardless of the presence of oocytes. Because BMP-7 changed neither FSK- nor cAMP-induced estradiol production, the BMP-7 action was mediated through a FSH receptor signaling mechanism that was independent of cAMP-protein kinase A pathway. Treatment with FSH but not cAMP activated ERK1/2 phosphorylation in granulosa cells, which was further accelerated by oocytes. A specific ERK inhibitor, U0126, increased estradiol production and decreased FSH- and FSK-induced progesterone production and cAMP synthesis. This suggests that ERK activation is directly linked to inhibition of estradiol synthesis and amplification of cAMP. Moreover, FSH-induced ERK1/2 phosphorylation was inhibited by BMP-7 but not influenced by BMP-6. In contrast, BMP signaling including Smad1/5/8 phosphorylation and Id-1 transcription was up-regulated by FSH and oocytes in granulosa cells through inhibition of Smad6/7 expression. Collectively, oocytes enhance FSH-induced MAPK activation and BMP signaling in granulosa cells, which leads to differential regulation of steroidogenesis elicited by BMPs in the presence of FSH in developing follicles.

DOI： 10.1210/en.2006-0966

Gastric Diverticulum Simulating Left Adrenal Incidentaloma in a Hypertensive Patient

Apparent mineralocorticoid excess manifested in an elderly patient with hypothyroidism. 査読国際誌

Inagaki K, Otsuka F, Otani H, Sato C, Miyoshi T, Ogura T, Makino H

American Journal of Hypertension 20 ( 1 ) 104 - 7 2007年1月

Primary Aldosteronism Caused by a Unilateral Adrenal Adenoma Accompanied by Autonomous Cortisol Secretion

Jiro SUZUKI, Fumio OTSUKA, Kenichi INAGAKI, Hiroyuki OTANI, Tomoko MIYOSHI, Tomohiro TERASAKA, Toshio OGURA, Masako OMORI, Yasutomo NASU, Hirofumi MAKINO

Hypertension Research 30 ( 4 ) 367 - 373 2007年

Ryo KODERA, Fumio OTSUKA, Kenichi INAGAKI, Tomoko MIYOSHI, Toshio OGURA, Yasushi TANIMOTO, Tetsuro SEI, Hirofumi MAKINO

Endocrine Journal 54 ( 6 ) 969 - 974 2007年

Mutual Regulation of Follicle-Stimulating Hormone Signaling and Bone Morphogenetic Protein System in Human Granulosa Cells1

Tomoko Miyoshi, Fumio Otsuka, Jiro Suzuki, Masaya Takeda, Kenichi Inagaki, Yoshihiro Kano, Hiroyuki Otani, Yukari Mimura, Toshio Ogura, Hirofumi Makino

Biology of Reproduction 74 ( 6 ) 1073 - 1082 2006年6月

Involvement of Bone Morphogenetic Protein-6 in Differential Regulation of Aldosterone Production by Angiotensin II and Potassium in Human Adrenocortical Cells

Kenichi Inagaki, Fumio Otsuka, Jiro Suzuki, Yoshihiro Kano, Masaya Takeda, Tomoko Miyoshi, Hiroyuki Otani, Yukari Mimura, Toshio Ogura, Hirofumi Makino

Endocrinology 147 ( 6 ) 2681 - 2689 2006年6月

Manifestation of Rheumatoid Arthritis after Transsphenoidal Surgery in a Patient with Acromegaly

Tomoko MIYOSHI, Fumio OTSUKA, Tomoko KAWABATA, Kenichi INAGAKI, Tomoyuki MUKAI, Masanori KAWASHIMA, Toshio OGURA, Masahiro YAMAMURA, Tetsuro SEI, Hirofumi MAKINO

Endocrine Journal 53 ( 5 ) 621 - 625 2006年

Induction of tumour necrosis factor receptor-expressing macrophages by interleukin-10 and macrophage colony-stimulating factor in rheumatoid arthritis

Koji Takasugi, Masahiro Yamamura, Mitsuhiro Iwahashi, Fumio Otsuka, Jiro Yamana, Katsue Sunahori, Masanori Kawashima, Masao Yamada, Hirofumi Makino

Arthritis Research & Therapy 8 ( 4 ) R126 - R126 2006年

Regulatory Roles of Bone Morphogenetic Proteins and Glucocorticoids in Catecholamine Production by Rat Pheochromocytoma Cells

Yoshihiro Kano, Fumio Otsuka, Masaya Takeda, Jiro Suzuki, Kenichi Inagaki, Tomoko Miyoshi, Manabu Miyamoto, Hiroyuki Otani, Toshio Ogura, Hirofumi Makino

Endocrinology 146 ( 12 ) 5332 - 5340 2005年12月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

DOI： 10.1210/en.2005-0474

An Extra-adrenal Abdominal Pheochromocytoma Causing Ectopic ACTH Syndrome

F OTSUKA, T MIYOSHI, K MURAKAMI, K INAGAKI, M TAKEDA, K UJIKE, T OGURA, M OMORI, H DOIHARA, Y TANAKA

American Journal of Hypertension 18 ( 10 ) 1364 - 1368 2005年10月

Essential Role of the Oocyte in Estrogen Amplification of Follicle-Stimulating Hormone Signaling in Granulosa Cells

Fumio Otsuka, R. Kelly Moore, Xia Wang, Shweta Sharma, Tomoko Miyoshi, Shunichi Shimasaki

Endocrinology 146 ( 8 ) 3362 - 3367 2005年8月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

Abstract

The establishment of dominant ovarian follicles that are capable of ovulating fertilizable oocytes is a fundamental determinant of female fertility. This process is governed by pituitary gonadotropins as well as local ovarian factors. Within the follicle, estrogen acts in an autocrine/paracrine manner to enhance FSH action in the granulosa cells. These effects include the augmentation of P450aromatase expression and estradiol production. This feed-forward effect of estrogen is believed to play a key role in follicle dominance. Here we found the essential role of the oocyte in this physiological process using primary cultures of rat granulosa cells. In the presence, but not absence, of oocytes, estrogen amplified FSH-stimulated increases in mRNA expression of P450aromatase, FSH receptor, LH receptor, and inhibin α-, βA-, and βB-subunits as well as cAMP production. Thus, oocytes mediate the estrogen enhancement of FSH action in the granulosa cells. In comparison with FSH, cotreatment with estrogen and oocytes failed to amplify the stimulatory effects of forskolin or 8-bromoadenosine-cAMP on granulosa cell responses including P450aromatase mRNA expression and cAMP production, indicating that estrogen/oocytes amplify FSH action at a site upstream of adenylate cyclase. These findings support the novel conclusion that communication between the oocyte and granulosa cells plays a crucial role in mediating estrogen action during FSH-dependent folliculogenesis.

DOI： 10.1210/en.2005-0349

Abrupt Enlargement of Adrenal Incidentaloma: A Case of Isolated Adrenal Metastasis

インスリン抵抗性と肥満を合併したバーター症候群の1例

村上和敏, 四方賢一, 和田淳, 大塚文男, 江口潤, 向井知之

糖尿病 48 ( 6 ) 464 - 464 2005年6月

Functional roles of the bone morphogenetic protein system in thyrotropin signaling in porcine thyroid cells

Jiro Suzuki, Fumio Otsuka, Masaya Takeda, Kenichi Inagaki, Tomoko Miyoshi, Yukari Mimura, Toshio Ogura, Hiroyoshi Doihara, Hirofumi Makino

Biochemical and Biophysical Research Communications 327 ( 4 ) 1124 - 1130 2005年2月

Octreotide effect on cluster headache in acromegaly patients

Fumio Otsuka, Satoshi Mizobuchi, Hirofumi Makino

EUROPEAN JOURNAL OF ENDOCRINOLOGY 152 2005年

Tomoko MIYOSHI, Fumio OTSUKA, Jiro SUZUKI, Kenichi INAGAKI, Yoshihiro KANO, Toshio OGURA, Katsuyuki KIURA, Takashi SAIKA, Hirofumi MAKINO

Endocrine Journal 52 ( 6 ) 785 - 788 2005年

Periodic Secretion of Adrenocorticotropin in a Patient with Cushing's Disease Manifested during Pregnancy

Tomoko MIYOSHI, Fumio OTSUKA, Jiro SUZUKI, Kenichi INAGAKI, Masaya TAKEDA, Yoshihiro KANO, Tetsuji YAMASHITA, Toshio OGURA, Isao DATE, Yasushi TANAKA, Kozo HASHIMOTO, Hirofumi MAKINO

Endocrine Journal 52 ( 3 ) 287 - 292 2005年

Effect of cabergoline treatment on Cushing’s disease caused by aberrant adrenocorticotropin-secreting macroadenoma

T. Miyoshi, F. Otsuka, M. Takeda, K. Inagaki, J. Suzuki, T. Ogura, I. Date, K. Hashimoto, H. Makino

Journal of Endocrinological Investigation 27 ( 11 ) 1055 - 1059 2004年12月

Characterization of the Bone Morphogenetic Protein (BMP) System in Human Pulmonary Arterial Smooth Muscle Cells Isolated from a Sporadic Case of Primary Pulmonary Hypertension: Roles of BMP Type IB Receptor (Activin Receptor-Like Kinase-6) in the Mitotic Action

Masaya Takeda, Fumio Otsuka, Kazufumi Nakamura, Kenichi Inagaki, Jiro Suzuki, Daiji Miura, Hideki Fujio, Hiromi Matsubara, Hiroshi Date, Tohru Ohe, Hirofumi Makino

Endocrinology 145 ( 9 ) 4344 - 4354 2004年9月

Aldosterone regulation for 18 years in a case of primary aldosteronism

Tomoko Miyoshi , Fumio Otsuka, Toshio Ogura, Jiro Suzuki, Kenichi Inagaki, Masaya Takeda, Masayuki Kishida, Yukari Mimura, Atsushi Nagai, Hirofumi Makino

American Journal of Hypertension 17 ( 6 ) 546 - 548 2004年6月

Cholestatic jaundice: An unusual symptom of isolated adrenocorticotropin deficiency in adults

F. Otsuka, K. Yamamoto, N. Shimada, J. Kageyama, T. Ogura, H. Makino

Journal of Endocrinological Investigation 27 ( 4 ) 404 - 405 2004年4月

Ovarian bone morphogenetic proteins in female reproduction

ShunichiShimasakiR.KellyMooreGregory, F.EricksonFumioOtsuka

International Congress Series 1266 241 - 247 2004年4月

Recent trends of hyperuricemia and obesity in Japanese male adolescents, 1991 through 2002

Toshio Ogura, Kazuharu Matsuura, Yosuke Matsumoto, Yukari Mimura, Masayuki Kishida, Fumio Otsuka, Kazuo Tobe

Metabolism 53 ( 4 ) 448 - 453 2004年4月

Novel Action of Activin and Bone Morphogenetic Protein in Regulating Aldosterone Production by Human Adrenocortical Cells

Jiro Suzuki, Fumio Otsuka, Kenichi Inagaki, Masaya Takeda, Toshio Ogura, Hirofumi Makino

Endocrinology 145 ( 2 ) 639 - 649 2004年2月

掲載種別：研究論文（学術雑誌）出版者・発行元：The Endocrine Society

Abstract

We have uncovered a functional bone morphogenetic protein (BMP) and activin system complete with ligands (BMP-6 and activin βA/βB), receptors (activin receptor-like kinase receptors 2, 3, and 4; activin type-II receptor; and BMP type-II receptor), and the binding protein follistatin in the human adrenocortical cell line H295R. Administration of activin and BMP-6 to cultures of H295R cells caused concentration-responsive increases in aldosterone production. The mRNA levels of steroidogenic acute regulatory protein or P450 steroid side-chain cleavage enzyme, the rate-limiting steps of adrenocortical steroidogenesis, were enhanced by activin and BMP-6. Activin and BMP-6 also activated the transcription of steroidogenic acute regulatory protein as well as the late-step steriodogenic enzyme CYP11B2. Activin enhanced ACTH-, forskolin-, or dibutyryl-cAMP- but not angiotensin II (Ang II)-induced aldosterone production, whereas BMP-6 specifically augmented Ang II-induced aldosterone production. Activin and ACTH but not BMP-6 increased cAMP production. Follistatin, which inhibits activin actions by binding, suppressed basal and ACTH-induced aldosterone secretion but failed to affect the Ang II-induced aldosterone level. Furthermore, MAPK signaling appeared to be involved in aldosterone production induced by Ang II and BMP-6 because an inhibitor of MAPK activation, U0126, reduced the level of aldosterone synthesis stimulated by Ang II and BMP-6 but not activin. In addition, Ang II reduced the expression levels of BMP-6 but increased that of activin βB, whereas ACTH had no effect on these levels. Collectively, the present data suggest that activin acts to regulate adrenal aldosterone synthesis predominantly by modulating the ACTH-cAMP-protein kinase A signaling cascade, whereas BMP-6 works primarily by modulating the Ang II-MAPK cascade in human adrenal cortex in an autocrine/paracrine fashion.

DOI： 10.1210/en.2003-0968

The bone morphogenetic protein system in mammalian reproduction

S Shimasaki, RK Moore, F Otsuka, GF Erickson

ENDOCRINE REVIEWS 25 ( 1 ) 72 - 101 2004年2月

記述言語：英語出版者・発行元：ENDOCRINE SOC

Using molecular, cellular, and genetic approaches, recent studies examining the role of the bone morphogenetic protein (BMP) family of growth factors in the reproductive system have led to significant breakthroughs in our understanding of mammalian reproduction and fertility. Gene expression studies have revealed that key components of the BMP system (ligands, receptors, signaling molecules, and binding proteins) exhibit coordinated spatial and temporal expression patterns in fundamental cell types throughout the reproductive system. Availability of recombinant BMPs has enabled functional studies that have demonstrated important biological activities of BMPs in controlling cellular proliferation, differentiation, and apoptosis in reproductive tissues. The physiological importance of the BMP system for mammalian reproduction has been further highlighted by the elucidation of the aberrant reproductive phenotypes of animals with naturally occurring mutations or targeted deletions of certain BMP family genes. Collectively, these studies have established the concept that the BMP system plays a crucial role in fertility in female and male mammals. The purpose of this article is to review the evidence underpinning the importance of the BMP system in mammalian reproduction.

DOI： 10.1210/er.2003-0007

An Aberrant ACTH-producing Ectopic Pituitary Adenoma in the Sphenoid Sinus

Jiro SUZUKI, Fumio OTSUKA, Toshio OGURA, Masayuki KISHIDA, Masaya TAKEDA, Takashi TAMIYA, Tatsuya NISHIOKA, Yasushi TANAKA, Kozo HASHIMOTO, Hirofumi MAKINO

Endocrine Journal 51 ( 1 ) 97 - 103 2004年

Long-term Effects of Octreotide on Pituitary Gigantism: Its Analgesic Action on Cluster Headache

Fumio OTSUKA, Satoshi MIZOBUCHI, Toshio OGURA, Kenji SATO, Masataka YOKOYAMA, Hirofumi MAKINO

Endocrine Journal 51 ( 5 ) 449 - 452 2004年

Effect of Etidronate on Intraosseous Meningioma

Kenichi INAGAKI, Fumio OTSUKA, Toshihiro MATSUI, Toshio OGURA, Hirofumi MAKINO

Endocrine Journal 51 ( 3 ) 389 - 390 2004年

Skull Paget's Disease Developing into Chiari Malformation

Fumio OTSUKA, Kenichi INAGAKI, Jiro SUZUKI, Toshio OGURA, Hirofumi MAKINO

Endocrine Journal 51 ( 3 ) 391 - 392 2004年

Reversible Pituitary Dysfunction in a Patient with Cushing's Syndrome Discovered as Adrenal Incidentaloma

Kenichi INAGAKI, Fumio OTSUKA, Tomoko MIYOSHI, Naomi WATANABE, Jiro SUZUKI, Toshio OGURA, Hirofumi MAKINO

Endocrine Journal 51 ( 2 ) 201 - 206 2004年

Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism

T. Ogura, Y. Mimura, Fumio Otsuka, M. Kishida, K. Yokota, J. Suzuki, A. Nagai, S. Hirakawa, H. Makino, K. Tobe

Journal of Endocrinological Investigation 26 ( 11 ) 1128 - 1135 2003年11月

Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas

Masaya Takeda, Fumio Otsuka, Jiro Suzuki, Masayuki Kishida, Toshio Ogura, Takashi Tamiya, Hirofumi Makino

Biochemical and Biophysical Research Communications 306 ( 4 ) 812 - 818 2003年7月

Effect of Intracellular Interactions on the Processing and Secretion of Bone Morphogenetic Protein-15 (BMP-15) and Growth and Differentiation Factor-9

Wu Xiang Liao, R. Kelly Moore, Fumio Otsuka, Shunichi Shimasaki

Journal of Biological Chemistry 278 ( 6 ) 3713 - 3719 2003年2月

Molecular Basis of Bone Morphogenetic Protein-15 Signaling in Granulosa Cells

R. Kelly Moore, Fumio Otsuka, Shunichi Shimasaki

Journal of Biological Chemistry 278 ( 1 ) 304 - 310 2003年1月

A Lethal Complication, Acute Necrotizing Pancreatitis, of Turner's Syndrome with Primary Hyperparathyroidism

Masayuki Kishida, Fumio Otsuka, Yukari Mimura, Toshio Ogura, Hirofumi Makino

Endocrine Journal 50 ( 6 ) 835 - 836 2003年

The role of bone morphogenetic proteins in ovarian function

S Shimasaki, RK Moore, GF Erickson, F Otsuka

REPRODUCTION 61,323-337 323 - 337 2003年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOSCIENTIFICA LTD

Bone morphogenetic proteins (BMPs) represent the largest subclass of growth factors in the transforming growth factor beta (TGF-beta) superfamily. BMPs have proven to be multifunctional regulators of a wide variety of biological processes in numerous types of cell and tissue. The role of inhibins, activins and TGF-betas (which also belong to the TGF-beta superfamily) in reproduction has been studied extensively over the last 15 years. However, there were no reports on the role of BMPs in the mammalian ovary until 1999 when we reported an intrinsic ovarian BMP system replete with BMP ligands, receptors and novel biological functions. Since this report it has become clear that the BMP system plays an important role in the regulation of ovarian function, evidenced by the ability of BMPs to control granulosa cell proliferation and cytodifferentiation, as well as oocyte development. The physiological relevance of the BMP system has recently been highlighted by the discovery that genetic mutations in the BMP-15 ligand or the BMPtype IB receptor lead to critical aberrations in folliculogenesis and ovulation. This review provides a current overview of the rapidly emerging field of the BMP system in mammalian ovarian function.

Relationship between Adrenomedullin and Vasopressin-Aquaporin System under General Anesthesia

Toshio Ogura, Kiyoshi Morita, Mamoru Takeuchi, Fumio Otsuka, Tatsuo Iwasaki, Katsunori Oe, Kazuharu Matsuura, Kazuo Tobe, Yukari Mimura, Masayuki Kishida, Hirofumi Makino, Masahisa Hirakawa

Hormone Research in Paediatrics 59 ( 1 ) 30 - 34 2003年

掲載種別：研究論文（学術雑誌）出版者・発行元：S. Karger AG

Aim: The roles of adrenomedullin (AM) in body fluid balance under general anesthesia were investigated. Methods: Time course changes in plasma osmolality, AM, arginine vasopressin (AVP), and urinary aquaporin 2 (AQP2) in 17 patients undergoing abdominal surgery under general anesthesia were examined. Results: Increases in plasma AM levels were observed in parallel with increases in the levels of urinary AQP2/creatinine (Cr) before induction and 90 and 180 min after initiation of anesthesia. Significant correlations between plasma AM and urinary AQP2/Cr (r = 0.62, p < 0.0001) as well as urinary AVP/Cr and AQP2/Cr (r = 0.60, p < 0.0001) were uncovered. Multivariate stepwise analysis identified plasma AM as the critical independent factor affecting urinary AQP2/Cr level. Conclusion: A novel correlation of AM and AQP2 which overlays an AVP-AQP2 system may play a key role in fluid homeostasis during general anesthesia.

DOI： 10.1159/000067933

A Novel Function of Bone Morphogenetic Protein-15 in the Pituitary: Selective Synthesis and Secretion of FSH by Gonadotropes

Role of Bradykinin in Renoprotective Effects by Angiotensin II Type 1 Receptor Antagonist in Salt-Sensitive Hypertension.

Kazuaki YOKOTA, Masayuki KISHIDA, Toshio OGURA, Jiro SUZUKI, Fumio OTSUKA, Yukari MIMURA, Masaya TAKEDA, Yoshio NAKAMURA, Hirofumi MAKINO

Hypertension Research 26 ( 3 ) 265 - 272 2003年

Fumio Otsuka, Shunichi Shimasaki

Endocrinology 143 ( 12 ) 4938 - 4941 2002年12月

A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: Its role in regulating granulosa cell mitosis

Fumio Otsuka, Shunichi Shimasaki

Proceedings of the National Academy of Sciences 99 ( 12 ) 8060 - 8065 2002年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：Proceedings of the National Academy of Sciences

Although the existence of a regulatory paracrine feedback system between oocytes and follicular somatic cells has been postulated for some time, there has not yet been any definitive evidence that such a communication system exists. Herein we present a previously undescribed oocyte-granulosa cell (GC) feedback communication system involving an oocyte-derived factor, bone morphogenetic protein-15 (BMP-15) and a GC-derived factor, kit ligand (KL), both of which have been shown to be crucial regulators of female reproduction. We used a coculture system of rat oocytes and GCs and found that BMP-15 stimulates KL expression in GCs, whereas KL inhibits BMP-15 expression in oocytes, thus forming a negative feedback loop. Moreover, KL, like BMP-15, exhibited mitotic activity on GCs in the presence of oocytes. Because c-kit (KL receptor) is expressed in oocytes but not GCs, the oocytes must be involved in mediating the KL-induced GC mitosis. Furthermore, the blockage of c-kit signaling in oocytes by using a c-kit neutralizing antibody markedly suppressed BMP-15-induced GC mitosis, suggesting that the oocyte must play a role in the GC responses to BMP-15. In contrast, the c-kit antibody had no effect on the mitotic activities of two other known GC mitogens, activin-A and BMP-7. Altogether, this study presents direct evidence of a negative feedback system governed by oocyte-derived BMP-15 and GC-derived KL, and demonstrates that the mitotic activities of BMP-15 and KL for GCs depend on this oocyte–GC communication system. We hypothesize that the negative feedback system most likely plays a pivotal role in early folliculogenesis.

DOI： 10.1073/pnas.122066899

Effect of Bone Morphogenetic Protein-7 on Folliculogenesis and Ovulation in the Rat1

Role of ERK1/2 in the Differential Synthesis of Progesterone and Estradiol by Granulosa Cells

R.Kelly Moore, Fumio Otsuka, Shunichi Shimasaki

Biochemical and Biophysical Research Communications 289 ( 4 ) 796 - 800 2001年12月

Follistatin Inhibits the Function of the Oocyte-Derived Factor BMP-15

Fumio Otsuka, R.Kelly Moore, Shun-ichiro Iemura, Naoto Ueno, Shunichi Shimasaki

Biochemical and Biophysical Research Communications 289 ( 5 ) 961 - 966 2001年12月

Woo-Sik Lee, Fumio Otsuka, R. Kelly Moore, Shunichi Shimasaki

Biology of Reproduction 65 ( 4 ) 994 - 999 2001年10月

Biological Function and Cellular Mechanism of Bone Morphogenetic Protein-6 in the Ovary

Fumio Otsuka, R. Kelly Moore, Shunichi Shimasaki

Journal of Biological Chemistry 276 ( 35 ) 32889 - 32895 2001年8月

Chronic treatment with amlodipine modulates adrenocortical angiotensin II receptors in spontaneously hypertensive rats

Masayuki Kishida, Fumio Otsuka, Toshio Ogura, Hideo Kataoka, Yoshio Nakamura, Takayoshi Yamauchi, Masami Takahashi, Kazuaki Yokota, Yukari Mimura, Hirofumi Makino

Life Sciences 69 ( 1 ) 113 - 122 2001年5月

Bone Morphogenetic Protein-15 Inhibits Follicle-stimulating Hormone (FSH) Action by Suppressing FSH Receptor Expression

Fumio Otsuka, Shin Yamamoto, Gregory F. Erickson, Shunichi Shimasaki

Journal of Biological Chemistry 276 ( 14 ) 11387 - 11392 2001年4月

The role of nitric oxide and the renin-angiotensin system in salt-restricted Dahl rats

Hideo Kataoka, Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Masayuki Kishida, Masami Takahashi, Yukari Mimura, Hirofumi Makino

American Journal of Hypertension 14 ( 3 ) 276 - 285 2001年3月

Coexistence of Graves' Disease and Struma Ovarii: Case Report and Literature Review.

YUKARI MIMURA, MASAYUKI KISHIDA, HISASHI MASUYAMA, NAOKO SUWAKI, JUNICHI KODAMA, FUMIO OTSUKA, HIDEO KATAOKA, TAKAYOSHI YAMAUCHI, TOSHIO OGURA, TAKAFUMI KUDO, HIROFUMI MAKINO

Endocrine Journal 48 ( 2 ) 255 - 260 2001年

Japanese Family with Glucocorticoid-Remediable Aldosteronism Diagnosed by Long-Polymerase Chain Reaction.

Kazuaki YOKOTA, Toshio OGURA, Masayuki KISHIDA, Jiro SUZUKI, Fumio OTSUKA, Yukari MIMURA, Tetsuya OISHI, Makizo HIRATA, Kazuo TOBE, Hirofumi MAKINO

Hypertension Research 24 ( 5 ) 589 - 594 2001年

Bone Morphogenetic Protein-15

Fumio Otsuka, Zuxu Yao, Taek-hoo Lee, Shin Yamamoto, Gregory F. Erickson, Shunichi Shimasaki

Journal of Biological Chemistry 275 ( 50 ) 39523 - 39528 2000年12月

Differential effect of chronic inhibition of calcium channel and angiotensin II type 1-receptor on aldosterone synthesis in spontaneously hypertensive rats 査読

F Otsuka, T Ogura, H Kataoka, M Kishida, M Takahashi, Y Mimura, T Yamauchi, H Makino

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 74 ( 3 ) 125 - 136 2000年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

We have investigated the in vivo effect of chronic blockade of Ca2+-channels and angiotensin II type I (AT(1))-receptors on aldosterone (Aldo)-synthesis in the adrenal glands of spontaneously hypertensive rats (SHR). Male SHR were administered Ca2+-antagonist, amlodipine (10 mg/kg per day) or AT(1)-receptor-antagonist, TCV-116 (1 mg/kg per day) from 7 until 11 weeks of age. Systolic blood pressure (SBP) and heart rate (HR) were significantly higher in SHR than Wistar-Kyoto (WKY) rats. Both treatments resulted in equivalent and significant reduction in SEP in SHR. Aldo-secretion in SHR, which was significantly higher than in WKY rats, was profoundly suppressed by TCV-116 compared with amlodipine. Both treatments resulted in thickening of the tuna glomerulosa, which immunohistochemically contains Aldo, at the end of therapy. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that CYP11A (P450scc) mRNA regulating the first step of Aldo-synthesis was significantly reduced from week 9 of age by amlodipine, and that CYP11A (P450aldo) mRNA regulating the last step of Aldo-synthesis was potently suppressed from 9 weeks of age by TCV-116. Our results indicate that chronic treatment with different antihypertensive agents directly modulates adrenocortical aldosterone synthesis in SHR in vivo via different mechanisms. (C) 2000 Elsevier Science Ltd. All rights reserved.

Testosterone modulates serum leptin concentrations in a male patient with hypothalamic hypogonadism

Effects of angiotensin-converting enzyme inhibitor and α1-adrenoceptor antagonist on hypertension induced in rats by long-term inhibition of nitric oxide production

M. Takahashi, F. Otsuka, T. Ogura, T. Yamauchi, H. Kataoka, M. Kishida, Y. Mimura, H. Makino

Clinical and Experimental Nephrology volume 126 - 132 2000年6月

T. Ogura, K. Tobe, Y. Mimura, F. Otsuka, T. Yamauchi, A. Imai, C. Tsukamoto, Y. Iwasaki, K. Matsuura

Journal of Endocrinological Investigation 23 ( 4 ) 246 - 250 2000年4月

Differential glomerular response to continuous infusion of vasopressin in spontaneously hypertensive rats and Wistar–Kyoto rats

Masayuki Kishida, Fumio Otsuka, Takayoshi Yamauchi, Toshio Ogura, Masami Takahashi, Hideo Kataoka, Yukari Mimura, Hirofumi Makino

Regulatory Peptides 87 ( 1-3 ) 25 - 32 2000年2月

Serum leptin correlates with serum uric acid but not serum testosterone in non-obese male adolescents

T Ogura, K Matsuura, F Otsuka, A Imai, C Tsukamoto, Y Mimura, Y Iwasaki, K Tobe

Res. Commun. Mol. Pathol. Pharmacol. 107 ( 1-2 ) 55-64 - 64 2000年1月

Pseudomalabsorption of Levothyroxine. A Case Report.

DAISUKE OGAWA, FUMIO OTSUKA, YUKARI MIMURA, AKIKO UENO, HIROO HASHIMOTO, MASAYUKI KISHIDA, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 47 ( 1 ) 45 - 50 2000年

Hyperthyroidism in a Patient with TSH-Producing Pituitary Adenoma Coexisting with Thyroid Papillary Adenocarcinoma.

MASAYUKI KISHIDA, FUMIO OTSUKA, HIDEO KATAOKA, KAZUAKI YOKOTA, TETSUYA OISHI, TAKAYOSHI YAMAUCHI, HIROYOSHI DOIHARA, TAKASHI TAMIYA, YUKARI MIMURA, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 47 ( 6 ) 731 - 738 2000年

Significant Gene Expression of Insulin-Like Growth Factor II and Proliferating Cell Nuclear Antigen in a Rapidly Growing Recurrent Pituitary ACTH-Secreting Adenoma

Kozo Hashimoto, Isao Nagano, Koichi Asaba, Mari Inoue, Tatsuya Nishioka, Toshihiro Takao, Takahito Nakajo, Takahisa Mori, Masahiro Kurisaka, Fumio Otsuka

Hormone Research in Paediatrics 54 ( 4 ) 198 - 202 2000年

掲載種別：研究論文（学術雑誌）出版者・発行元：S. Karger AG

Background: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurred very rapidly as invasive macroadenoma. Methods/Results: A 43-year-old woman underwent successful transsphenoidal surgery for Cushing’s disease. Seven years later, she was admitted to our ward for further endocrine examinations. In spite of a very high plasma ACTH level, the serum cortisol level was normal. Discrepancies between ACTH and cortisol levels were detected on the basis of diurnal rhythms, dexamethasone suppression tests, and corticotropin-releasing hormone test. The patient showed no clinical features of Cushing’s disease. Magnetic resonance imaging of the pituitary showed an almost empty sella, and no microadenoma was found. These results, along with those of Sephadex column gel filtration and high-performance liquid chromatography of plasma-immunoreactive ACTH, suggested that the patient’s residual corticotrophs secreted biologically inactive ACTH. Two years later, the patient suddenly developed diplopia and right abducens nerve palsy. She was slightly moonfaced and centrally obese. Her plasma ACTH and serum and urinary free cortisol levels were elevated, although discrepancies between ACTH and cortisol still existed. Magnetic resonance imaging revealed a large pituitary mass with suprasellar and cavernous sinus extensions. The tumor was excised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region of the proopiomelanocortin gene. A significant expression of insulin-like growth factor II and proliferating cell nuclear antigen mRNAs was demonstrated. A high MIB-1 antibody labeling index was also detected in the adenoma tissue, suggesting high Ki-67 expression. Conclusion: These growth- and proliferation-related factors might be involved in the rapid growth and aggressiveness of this patient’s pituitary adenoma.

DOI： 10.1159/000053259

Chronic Treatment with Angiotensin II Type 1 Receptor Antagonist Suppresses Glomerular Activator Protein–1 Activity in Salt–Sensitive Hypertensive Rats

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Minoru Sato, Hideo Kataoka, Jingo Kageyama, Hirofumi Makino

Kidney and Blood Pressure Research 23 ( 1 ) 35 - 41 2000年

掲載種別：研究論文（学術雑誌）出版者・発行元：S. Karger AG

We examined the effects of angiotensin–converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT1a) on the action of protooncogene c–fos in salt–sensitive hypertensive rats. Seven–week old Dahl salt–sensitive rats fed a high (8%)–salt diet were treated with ACEI, cilazapril (10 mg/kg) or AT1a, TCV–116 (1mg/ kg) every day for 6 weeks. The control animals were fed a low (0.3%)–salt diet. Systolic blood pressure gradually increased in high–salt–loaded rats and was higher than low–salt–treated rats throughout the study. However, both medications had no significant antihypertensive effect. After 6 weeks of therapy, glomerular mRNA and nuclear protein were extracted from the resected kidneys. Competitive reverse transcription–polymerase chain reaction showed a high level of glomerular c–fos mRNA in high–salt–loaded rats and that ACEI or AT1a treatment did not significantly change its level. Electrophoretic mobility shift assay demonstrated that treatment with AT1a significantly decreased the activator protein–1 (AP–1) binding activity in the glomerular nuclear extract compared to ACEI. Our findings suggest that, compared with ACEI treatment, long–term treatment with AT1a may contribute to attenuation of the glomerular injury in salt–sensitive hypertension by inhibiting AP–1 transcription activity independent of its antihypertensive effect.

DOI： 10.1159/000025952

Sevoflurane anesthesia causes a transient decrease in aquaporin-2 and impairment of urine concentration.

Kiyoshi Morita, *Fumio Otsuka, Toshio Ogura, Mamoru Takeuchi, Satoshi Mizobuchi, Takayoshi Yamauchi, Hirofumi Makino and Masahisa Hirakawa

Br. J. Anaesth. 83 ( 5 ) 734 - 739 1999年11月

Quantitative analysis of growth-related factors in human pituitary adenomas

Fumio Otsuka, Takashi Tamiya, Takayoshi Yamauchi, Toshio Ogura, Takashi Ohmoto, Hirofumi Makino

Regulatory Peptides 83 ( 1 ) 31 - 38 1999年8月

Long-term administration of adrenocorticotropin modulates the expression of IGF-I and TGF-β1mRNAs in the rat adrenal cortex

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Hideo Kataoka, Masayuki Kishida, Nobuyuki Miyatake, Yukari Mimura, Jingo Kageyama, Hirofumi Makino

Growth Hormone & IGF Research 9 ( 1 ) 41 - 51 1999年2月

The Effects of Intrinsic Vasopressin on Urinary Aquaporin-2 Excretion and Urine Osmolality During Surgery Under General Anesthesia

Fumio Otsuka, Kiyoshi Morita, Mamoru Takeuchi, Takayoshi Yamauchi, Toshio Ogura, Kyouichi Sekine, Masakazu Miura, Masahisa Hirakawa, Hirofumi Makino

Anesthesia & Analgesia 88 ( 1 ) 181 - 187 1999年1月

An Elderly Patient with Transient Diabetes Insipidus Associated with Lymphocytic Infundibulo-Neurohypophysitis.

MASAMI TAKAHASHI, FUMIO OTSUKA, TOMOKO MIYOSHI, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 46 ( 5 ) 741 - 746 1999年

A case of idiopathic deep vein thrombosis improved with glucocorticoid therapy

F Otsuka, T Amano, H Uchida, T Ogura, H Makino

Haematologia (Budap) 29 ( 4 ) 305 - 312 1999年

Giant Insulinoma in a Patient with Multiple Endocrine Neoplasia-Type I. A Case report.

HIDEO KATAOKA, FUMIO OTSUKA, TAKAYOSHI YAMAUCHI, MASAYUKI KISHIDA, MASAMI TAKAHASHI, TAKASHI TAMIYA, YUKARI MIMURA, TOSHIO OGURA, HIROFUMI MAKINO

Endocrine Journal 46 ( 3 ) 429 - 435 1999年

Treatment with a Ca2+ Channel Blocker, Barnidipine, Reduces Platelet-Derived Growth Factor B-Chain mRNA in Glomeruli of Spontaneously Hypertensive Rats

Masami Hashimoto, Takayoshi Yamauchi, Toshio Ogura, Tetsuya Oishi, Yukari Mimura, Fumio Otsuka, Naoki Kashihara, Hirofumi Makino

American Journal of Nephrology 19 ( 5 ) 615 - 621 1999年

掲載種別：研究論文（学術雑誌）出版者・発行元：S. Karger AG

We investigated the effect of barnidipine hydrochloride, a Ca2+ channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-β1 in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-β1 mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

DOI： 10.1159/000013511

Congenital Adrenal Hyperplasia With Normokalemic Periodic Paralysis

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Hirofumi Makino

Archives of Neurology 55 ( 11 ) 1487 - 1487 1998年11月

Renal c-fos expression induced by angiotensin II is enhanced in spontaneously hypertensive rats

Fumio Otsuka, Takayoshi Yamauchi, Toshio Ogura, Masami Takahashi, Jingo Kageyama, Hirofumi Makino

Life Sciences 63 ( 23 ) 2089 - 2095 1998年10月

Hormonal characteristics of primary aldosteronism due to unilateral adrenal hyperplasia

Fumio Otsuka, F. Otsuka-Misunaga, S. Koyama, H. Yamanari, T. Ogura, T. Ohe, H. Makino

Journal of Endocrinological Investigation 21 ( 8 ) 531 - 536 1998年9月

Cluster headache dependent upon octreotide injection

F Otsuka, J Kageyama, T Ogura, H Makino

Headache: The Journal of Head and Face Pain 38 ( 8 ) 629 - 631 1998年9月

Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in Dahl salt-sensitive rats.

*Fumio Otsuka, Takayoshi Yamauchi, Hideo Kataoka, Yukari Mimura, Toshio Ogura and Hirofumi Makino

Am. J. Physiol. 274 ( 6 ) R1797 - R1806 1998年6月

Effect of continuous infusion of vasopressin on glomerular growth response in spontaneously hypertensive rats

Kazushi Harada, Toshio Ogura, Takayoshi Yamauchi, Fumio Otsuka, Yukari Mimura, Masami Hashimoto, Tetsuya Oishi, Hirofumi Makino

Regulatory Peptides 74 ( 1 ) 11 - 18 1998年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

Vasopressin (VP) is thought to play an important role in the presser and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta 1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the II-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta 1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta 1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta 1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease. (C) 1998 Published by Elsevier Science B.V.

DOI： 10.1016/s0167-0115(98)00009-3

Reversible Hypothyroidism in Empty Sella Syndrome: A Case Report.

Sheehan's syndrome of more than 30 years' duration: an endocrine and MRI study of 6 cases

Fumio Otsuka, Jingo Kageyama, Toshio ogura, Teruhiko Hattori, Hirofumi makino

Endocr. J. 45 451-458 1998年1月

Renal AT1 receptor: autoradiographic localization and quantification in rat

N Asano, T Ogura, Y Mimura, M Kishida, H Kataoka, F Otsuka, T Yamauchi, H Makino

Res. Commun. Mol. Pathol. Pharmacol. 100 ( 2 ) 161-170 - 170 1998年1月

Renal AT1 receptor: computerized quantification in spontaneously hypertensive rats and DOCA-salt rats

N Asano, T Ogura, Y Mimura, F Otsuka, M Kishida, M Hashimoto, T Yamauchi, H Makino

Res. Commun. Mol. Pathol. Pharmacol. 100 ( 2 ) 171-180 - 180 1998年1月

FUMIO OTSUKA, TOSHLO OGURA, NOBUHIKO HAYAKAWA, SEISHI HARADA, JINGO KAGEYAMA, HIROFUMI MAKINO

Endocrine Journal 45 ( 3 ) 385 - 391 1998年

Cushing's Syndrome due to Unilateral Adrenocortical Hyperplasia.

Fumio OTSUKA, Toshio OGURA, Kazushi NAKAO, Nobuhiko HAYAKAWA, Yukari MIMURA, Takayoshi YAMAUCHI, Hirofumi MAKINO

Internal Medicine 37 ( 4 ) 385 - 390 1998年

Hypocalcemia due to Spontaneous Infarction of Parathyroid Adenoma and Osteomalacia in a Patient with Primary Hyperparathyroidism.

FUMIO OTSUKA, TOSHIO OGURA, TORU SATO, NOBUHIKO HAYAKAWA, YUKARI MIMURA, MASAYUKI KISHIDA, TAKAYOSHI YAMAUCHI, HIROFUMI MAKINO

Endocrine Journal 45 ( 5 ) 617 - 623 1998年

Pituitary Apoplexy Induced by a Combined Anterior Pituitary Test: Case Report and Literature Review.

FUMIO OTSUKA, JINGO KAGEYAMA, TOSHLO OGURA, HIROFUMI MAKINO

Endocrine Journal 45 ( 3 ) 393 - 398 1998年

Sheehan's Syndrome of More Than 30 Years' Duration: An Endocrine and MRI Study of 6 Cases.

FUMIO OTSUKA, JINGO KAGEYAMA, TOSHIO OGURA, TERUHIKO HATTORI, HIROFUMI MAKINO

Endocrine Journal 45 ( 4 ) 451 - 458 1998年

Effects of OPC-21268, a vasopressin V1-receptor antagonist, on glomerular injury in spontaneously hypertensive rats.

*Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Yukari Mimura and Hirofumi Makino

Regul. Pept. 72 ( 2-3 ) 87 - 95 1997年10月

Postanesthetic Polyuria Attributable to Central Diabetes Insipidus

Fumio Otsuka, Satoshi Mizobuchi, Kiyoshi Morita, Hideo Matsumoto, Toshio Ogura, Masahisa Hirakawa, Hirofumi Makino

Anesthesia & Analgesia 85 ( 4 ) 940 - 943 1997年10月

In vitro macro- and microautoradiographic localization of V1 and V2 receptors in the rat kidney using OPC-21268 and OPC-31260. 査読

Yukari Mimura, Toshio Ogura, Nobuhiko Hayakawa, *Fumio Otsuka, Masami Hashimoto, Takayoshi Yamauchi, Hirofumi Makino and Norio Ogawa

Nephron 76 ( 3 ) 331 - 336 1997年

IDDM accompanied a growth hormone-producing pituitary adenoma: A case report 査読

Fumio Otsuka, Toshio Ogura, Takayoshi Yamauchi, Kenichi Shikata, Jingo Kageyama, Hirofumi Makino

Diabetes Care 20 ( 12 ) 1838 - 1841 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Diabetes Association Inc.

CASE HISTORY - A 30-year-old Japanese man who presented with recurrent ketoacidosis caused by IDDM was found to have increased secretion of growth hormone (GH). On initial cranial magnetic resonance imaging (MRI), no pituitary lesion was detected
however, a pituitary microadenoma was found 2 years later during a repeat MRI. In spite of the hypersecretion of GH, serum IGF-I was dramatically suppressed. Transsphenoidal surgery was performed to resect the pituitary tumor that was histologically an acidophilic pituitary adenoma. Although the GH excess rapidly improved postoperatively, the IGF-I level remained low. Subsequent insulin therapy initiated 1 year after the operation elevated the serum IGF-I level to within the normal range. DISCUSSION - The first case of coexistent IDDM and a GH-producing pituitary adenoma suggests that patients with uncontrolled IDDM may develop GH hypersecretion. Furthermore, the low IGF-I levels may be closely associated with the GH excess and with the development or progression of GH-secreting pituitary adenomas.

DOI： 10.2337/diacare.20.12.1838

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