The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 251, Issue 2
June
Displaying 1-8 of 8 articles from this issue
Regular Contribution
  • Yuji Wakayama, Makoto Nakano, Koji Fukuda, Koji Kumagai, Yoshinao Suga ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 2 Pages 69-79
    Published: 2020
    Released on J-STAGE: June 04, 2020
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    Cardiac resynchronization therapy (CRT) improves cardiac dyssynchrony in heart failure patients with a wide QRS electrocardiogram (ECG). Assessment of left ventricular (LV) dyssynchrony using echocardiography or other imaging modalities is important to predict CRT effectiveness. In this study, we retrospectively evaluated cardiac nuclear imaging of ECG-gated myocardial perfusion single-photon emission computed tomography (SPECT) with 99mTc-sestamibi for CRT candidate (n = 120) with severe heart failure and wide QRS (> 120 msec) in ECG. To analyze LV non-uniformity, we used the quantitative gated SPECT (QGS) software to calculate changes in regional LV wall thickness during a cardiac cycle (i.e., wall thickening scores). Cardiac events (heart failure, ventricular arrhythmias and cardiac death) after CRT during 38 ± 22 (SD) months were also evaluated. In 97 of 120 patients who underwent QGS before and 6 months after CRT, CRT homogenized non-uniform wall thickening between septal and lateral of the LV especially in CRT responders. This observation was indicated as increase in the lateral deflection (XWT) of wall thickening scores before CRT and its decrease after CRT. In 120 patients with QGS before CRT, the larger XWT before CRT (≥ 16.5) predicted better prognoses after CRT. This finding was similarly observed even in patients with narrower baseline QRS (≤ 140 msec; n = 41 of 120), who usually have less benefits from CRT. In conclusion, CRT improved non-uniformity of wall thickening between the LV septal and lateral regions evaluated using QGS, which is predictive of better prognosis in the chronic phase after CRT.

Case
  • Kazuharu Kamachi, Toshihiko Ando, Nanae Tsuruoka, Mariko Hashiguchi, K ...
    Article type: Case
    2020 Volume 251 Issue 2 Pages 81-85
    Published: 2020
    Released on J-STAGE: June 05, 2020
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    Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic stem cell transplantation (Allo-SCT). Chronic GVHD, which typically presents more than 100 days after Allo-SCT, can resemble manifestations of autoimmune disease; however, there are only a few reports on the development of Crohn’s disease (CD) after Allo-SCT. Here, we report a case of steroid-refractory CD after umbilical cord blood transplantation (CBT), which was dramatically improved with administration of anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibodies. A 21-year-old woman with refractory Hodgkin lymphoma underwent CBT and achieved complete remission. About 1 year after CBT, she complained of intermittent abdominal pain and bloody diarrhea, and colonoscopy revealed multiple longitudinal colonic ulcers with a cobblestone appearance; thus, based on the colonoscopy findings, she was diagnosed with CD. We considered a CD-like manifestation of gastrointestinal GVHD and initially administered steroids, but the therapeutic effect was poor. Then, we administered anti-TNF-alpha antibodies, infliximab, and then adalimumab, which resulted in rapid improvement of abdominal symptoms, with no recurrence despite discontinuation of this therapy. Anti-TNF-alpha antibodies are effective for CD after Allo-SCT, which can be considered as a subsequent complication of GVHD.

Review
  • Eikan Mishima, Naohiko Anzai, Mariko Miyazaki, Takaaki Abe
    Article type: Review
    2020 Volume 251 Issue 2 Pages 87-90
    Published: 2020
    Released on J-STAGE: June 12, 2020
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    In light of the recent pandemic, favipiravir (Avigan®), a purine nucleic acid analog and antiviral agent approved for use in influenza in Japan, is being studied for the treatment of coronavirus disease 2019 (COVID-19). Increase in blood uric acid level is a frequent side effect of favipiravir. Here, we discussed the mechanism of blood uric acid elevation during favipiravir treatment. Favipiravir is metabolized to an inactive metabolite M1 by aldehyde oxidase and xanthine oxidase, and excreted into urine. In the kidney, uric acid handling is regulated by the balance of reabsorption and tubular secretion in the proximal tubules. Favipiravir and M1 act as moderate inhibitors of organic anion transporter 1 and 3 (OAT1 and OAT3), which are involved in uric acid excretion in the kidney. In addition, M1 enhances uric acid reuptake via urate transporter 1 (URAT1) in the renal proximal tubules. Thus, favipiravir is thought to decrease uric acid excretion into urine, resulting in elevation of uric acid levels in blood. Elevated uric acid levels were returned to normal after discontinuation of favipiravir, and favipiravir is not used for long periods of time for the treatment of viral infection. Thus, the effect on blood uric acid levels was subclinical in most studies. Nevertheless, the adverse effect of favipiravir might be clinically important in patients with a history of gout, hyperuricemia, kidney function impairment (in which blood concentration of M1 increases), and where there is concomitant use of other drugs affecting blood uric acid elevation.

    Editor's pick

    Review Article: Favipiravir

Regular Contribution
  • Yusuke Hiratsuka, Maho Aoyama, Taiko Kaneta, Kento Masukawa, Keita Tag ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 2 Pages 91-96
    Published: 2020
    Released on J-STAGE: June 23, 2020
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    Providing spiritual care in light of a patient’s religious and/or spiritual background can help improve the quality of end-of-life care. Rinsho-shukyo-shi is a Japanese interfaith chaplain who provides religious and spiritual care to patients. In this study, we qualitatively explore the impressions of patients in a palliative care unit of the activities of an interfaith chaplain in a hospital in Japan. The authors used semi-structured interviews carried out by a male nurse experienced in qualitative and quantitative research in palliative care. The male nurse asked only a few predetermined questions in the interviews, which were conducted from January 19 to December 26, 2018. The interviewees were 15 patients diagnosed with advanced cancer (five men and 10 women; aged 53-81 years), and they were admitted to the palliative care unit of Tohoku University Hospital (the hospital has no religious affiliation). Patients who had spoken to the interfaith chaplain at the hospital at least twice were included in the study. The interviews were digitally audio-recorded, transcribed verbatim, and analyzed. Three main themes were identified through thematic analysis. Resistance varied across patients; no patient felt resistance to the intervention by, or to the presence of, the interfaith chaplain once he/she had spoken with him. Opinions about the interfaith chaplain also varied, with 10 patients claiming that his role was necessary for end-of-life care and beneficial for the chaplain himself. Finally, the patients’ religious beliefs varied widely. In conclusion, the interfaith chaplain is deemed helpful by the interviewed patients in relieving their anxieties.

  • Akito Tsuboi, Hiroyuki Matsui, Naru Shiraishi, Takahisa Murakami, Akih ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 2 Pages 97-115
    Published: 2020
    Released on J-STAGE: June 23, 2020
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    In order to assess the long-term impact of the Great East Japan Earthquake on the oral health of disaster victims and to evaluate gene-environmental interactions in the development of major oral diseases and oral-systemic associations, the oral part of two large-scale genome cohort studies by the Tohoku Medical Megabank Organization (ToMMo), including the Community-based cohort (CommCohort) study and the Birth and Three-Generation cohort (BirThree) study, have been conducted. The study population comprised 32,185 subjects, including 16,886 participants in the CommCohort study and 15,299 participants in the BirThree cohort study, recruited from 2013 to 2017. The oral studies consist of a questionnaire regarding oral hygiene behavior, clinical examinations by dentists, and oral plaque and saliva sampling for microbiome analyses, which were carried out at seven community support centers in Miyagi prefecture. The median age of all participants was 55.0 years, and 66.1% of participants were women. Almost all participants reported that they brushed their teeth more than once a day. The median number of present teeth was 27.0, and the decayed, missing and filled tooth number was 16.0, with a significant difference according to age and sex. The median periodontal pocket and clinical attachment level was 2.48 mm and 4.00 mm, respectively. Periodontal parameters increased significantly according to age, except for the accumulation of dental calculus. The oral part of these extensive cross-sectional studies provides a unique and important platform for future studies on oral health and diseases that elicit through interactions with systemic diseases, lifestyles, life events and genetic backgrounds, and contributes to researches clarifying the long-term effects of disasters on oral health.

  • Taejun Yoon, Sung Soo Ahn, Juyoung Yoo, Byung-Woo Yoo, Hyeok Chan Kwon ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 2 Pages 117-123
    Published: 2020
    Released on J-STAGE: June 23, 2020
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    Mannose-binding lectin (MBL) is a soluble pattern-recognition molecule, which plays a crucial role in the innate immune system and the activation of lectin complement pathway. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease affecting the small vasculatures and is characterized by the alteration of innate and adaptive immunity and complement activation. In this study, we investigated whether serum MBL is associated with disease activity of AAV, which was measured by ELISA. Associations between serum MBL and AAV-specific indices, as well as clinical and laboratory data were assessed using Kendall’s tau. Among the 80 patients, 42 (52.5%), 21 (26.3), and 17 (21.3%) patients were classified as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), respectively. The median values of erythrocyte sedimentation rate, C-reactive protein, and serum MBL were 36.5 (normal range < 20) mm/h, 2.4 (normal range < 8) mg/dL, and 8.6 ng/mL, respectively. The median serum levels of MBL in MPA, GPA, and EGPA patients were 8.4, 9.3, and 8.2 ng/mL. Correlation analysis showed that serum MBL was associated with Birmingham Vasculitis Activity Score (BVAS) (R = 0.169, p = 0.027), but not with other AAV-specific indices and clinical and laboratory data. In addition, serum MBL was significantly associated with the pulmonary manifestation score based on BVAS (R = 0.247, p = 0.001). In summary, among the AAV-specific indices and clinical and laboratory variables analyzed, serum MBL is correlated with BVAS and pulmonary manifestation score based on the BVAS.

  • Soshi Okazaki, Ryu Watanabe, Hinako Kondo, Masataka Kudo, Hideo Hariga ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 2 Pages 125-133
    Published: 2020
    Released on J-STAGE: June 25, 2020
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    Polymyalgia rheumatica (PMR) is an inflammatory disorder in the elderly and is characterized by pain in the shoulders and lower back. Previous studies from western countries have shown that relapse is frequent; however, there are only a few reports on the relapse rate in Japan. Here we examined the relapse rate, and sought to identify factors that predict recurrence in patients with PMR. Of 110 patients who fulfilled the Bird’s criteria for PMR between May 2011 and June 2019, 21 patients were excluded, and the remaining 89 patients were followed up until July 2019. Relapse was defined when clinical symptoms were exacerbated and serum C-reactive protein level increased. The relapse-free survival curves were plotted using the Kaplan-Meier method, and log-rank test was used for statistical analysis. The mean age of the 89 patients (50 males and 39 females) was 71.8 years. The mean dose of initial prednisolone (PSL) was 11.8 mg/day. The 1-, 3-, and 5-year relapse-free survival rates were 81.6%, 58.0%, and 52.3% (N = 59, 21, and 7), respectively. In patients who experienced recurrence, the 1- and 3-year second relapse-free survival rates were 58.3% and 27.3% (N = 18 and 3), respectively. Immunosuppressants, such as methotrexate and tacrolimus, were added to PSL in 19 of 30 patients who experienced relapse at the discretion of the attending physicians; however, none of the immunosuppressants worked for preventing second relapses and had steroid-sparing effects. These results indicate that effective immunosuppressants are required to suppress relapse in the treatment of PMR.

  • Toshihiro Ishii, Seiji Shiota, Kyoko Yamamoto, Koh Abe, Eishi Miyazaki
    Article type: Regular Contribution
    2020 Volume 251 Issue 2 Pages 135-145
    Published: 2020
    Released on J-STAGE: June 27, 2020
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    The high rates of mortality and hospitalization among elderly asthmatics, as well as their increasing healthcare costs have become an important public health issue. It would be worthwhile to assess whether inhaled corticosteroid (ICS) can resolve these problems. To explore ICS prescription rates for elderly asthmatics and the factors influencing them and to investigate their association with hospitalization and healthcare costs, we analyzed data from the National Health Insurance Claims Database for the same time frame (December 1 to February 28) across three different periods (2011-2012; 2014-2015; and 2017-2018), from which we identified 6,619, 5,619, and 6,880 elderly individuals, respectively. The prescription rates of ICS increased (52.8%, 65.5% and 68.8%, in the first, second and third survey period, respectively) and inversely the hospital admission rates declined (3.7%, 3.2% and 2.5%, in the first, second and third survey period, respectively). The total healthcare costs per month were significantly lower for patients who received ICS-containing regimens than for those who did not. A multivariate analysis revealed that increasing age, rural residence, receiving a prescription from a clinic, hospital admission, and prescription of asthma medications other than ICS were associated with non-prescription of ICS, whereas cross-boundary treatment increased the ICS-prescription rate. Our study suggests that increases in the prescription rate of ICS are associated with reduced hospital admission rates and lower medical costs in the real-world. ICS prescription rates in rural areas and at clinics, which remain low, need to be increased.

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