The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 251, Issue 1
May
Displaying 1-9 of 9 articles from this issue
Regular Contribution
  • Ryo Ikesu, Atsushi Miyawaki, Yasuki Kobayashi
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 1-8
    Published: 2020
    Released on J-STAGE: May 01, 2020
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    As the medical demand is projected to increase along with the population aging in Japan, the geographical distribution of physicians is a significant concern for society and policymakers. To implement effective measures on geographical physician distribution, this study aimed to describe and compare the distribution of physicians by specialty in 2000, 2010 and 2016 in Japan, and examine whether practice setting was associated with distribution. To quantify the geographical physician distribution by specialty, we calculated the Gini coefficients of physicians working at clinics or hospitals in 2000, 2010, and 2016. We used the basic geographic unit for medical care planning in Japan, a secondary medical area, as the study unit. To show the association between the geographical distribution of physicians in each specialty and their practice setting, we categorized specialties into two groups by the proportion of physicians in that specialty working in hospitals, and showed aggregated Lorenz curves for each category. The overall geographical distribution of physicians appeared to improve during the study period, but varied by specialty. Those in specialties, where at least 90% of physicians work in hospitals such as anesthesiologists and radiologists, were more clustered, as shown by the Lorenz curves and the Gini coefficients. Similar distributional differences were also found even when we excluded physicians working in clinics, meaning that the distributional variation could be explained by other factors than the distribution of hospitals. These results suggest that the nature of practice in each specialty strongly affects the geographical distribution of specialists.

  • Naoki Kondo, Junichi Fujisawa, Naoto Endo
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 9-18
    Published: 2020
    Released on J-STAGE: May 14, 2020
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    Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic articular and bone manifestations and its pathogenesis is driven by a complex network of proinflammatory cytokines, including tumor necrosis factor and interleukin (IL)-6. Treatment of rheumatoid arthritis (RA) has been standardized by the introduction of a treat-to-target approach. Subcutaneous tocilizumab (TCZ-SC) is a humanized anti-IL-6 receptor monoclonal antibody, and is widely used for refractory RA patients in the clinical settings. However, it remains unknown whether TCZ-SC shows effectiveness for elderly onset RA. The study was aimed to assess the effectiveness and safety of TCZ-SC in elderly-onset rheumatoid arthritis (EORA) patients in daily practice. Fifty-five RA patients were divided into two age groups upon TCZ-SC administration: young (Y) group (< 65 years old, n = 30) and elderly-onset (EO) group (> 65 years old, n = 25). Disease activity score-28 (DAS28) upon TCZ-SC administration (4.84 in EO group vs. 4.41 in Y group) was significantly decreased to 1.94 vs. 1.93 at 3 months and 1.61 vs. 1.75 at 12 months after administration. The clinical remission (DAS28 < 2.6) rate was 75% in EO group vs. 83% in Y group at 3 months and 90% vs. 85% at 12 months. The retention rate at 12 months was 88% in EO group and 92% in Y group without significant difference. The cessation cases of adverse events were two in each group. In conclusion, TCZ-SC showed good clinical effectiveness and safety in EORA patients. TCZ-SC is a useful agent for patients with EORA.

  • Yutaka Yabe, Yoshihiro Hagiwara, Takuya Sekiguchi, Yumi Sugawara, Masa ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 19-26
    Published: 2020
    Released on J-STAGE: May 19, 2020
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    Musculoskeletal pain is a major problem among survivors of natural disasters. Functional disabilities in older adults increase after disasters and can lead to musculoskeletal pain. However, the effects of poor physical function on musculoskeletal pain after natural disasters remain unclear. This study aimed to elucidate the association of poor physical function with new-onset musculoskeletal pain among older survivors after the Great East Japan Earthquake (GEJE). Survivors aged ≥ 65 years, 3 years after the GEJE, were assessed longitudinally for 1 year (n = 646). Musculoskeletal pain was assessed using a self-reported questionnaire, and new-onset musculoskeletal pain was defined as absence and presence of pain at 3 years and 4 years, respectively, after the disaster. Physical function at 3 years after the disaster was assessed using the Kihon Checklist physical function score, which consists of 5 yes/no questions, and poor physical function was defined as a score of ≥ 3/5. Multivariate logistic regression analyses were used to assess the association of poor physical function with new-onset musculoskeletal pain. The incidence of new-onset musculoskeletal pain was 22.4%. Participants with poor physical function had a significantly higher rate of new-onset musculoskeletal pain. Compared with high physical function, the adjusted odds ratio (95% confidence interval) for new-onset musculoskeletal pain was 2.25 (1.37-3.69) in poor physical function (P = 0.001). Preceding poor physical function was associated with new-onset musculoskeletal pain among older survivors after the GEJE. There is need to focus on the maintenance of physical function to prevent musculoskeletal pain after natural disasters.

  • Mutsuo Yamaya, Hidekazu Nishimura, Xue Deng, Akiko Kikuchi, Ryoichi Na ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 27-30
    Published: 2020
    Released on J-STAGE: May 22, 2020
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    The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 μg/mL) or nafamostat (0.01-1 μg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.

    Editor's pick

    Original Article: COVID-19

  • Yi Fan Wang, Jun Zhao, Janos Negyesi, Ryoichi Nagatomi
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 31-37
    Published: 2020
    Released on J-STAGE: May 20, 2020
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    Motor skill practice improves performance not only in the trained - but also in the untrained contralateral limb - a phenomenon called as interlimb transfer. Handedness affects motor skill acquisition and interlimb transfer, but it remains unknown whether handedness affects interlimb transfer when practicing with the dominant or non-dominant limb. We have hypothesized that interlimb transfer of skill acquisition differs between left- and right-handed participants, and that right- as compared with left-hand motor skill practice shows greater interlimb transfer, regardless of handedness. Strongly left-hand (n = 12, aged 27.3 ± 4.4 years; 3 female) and right-hand dominant (n = 12, 20.7 ± 3.8 years; 5 female) subjects with no history of neurological or orthopedic disorders performed the grooved pegboard test before and after 4 blocks of practice on the same apparatus. Subjects were timed on their speed of the task. Right-handed subjects failed to improve manual performance in their right hand after right- or left-hand motor practice. In contrast, they showed improvement on the left hand in each condition. These data suggest greater interlimb transfer after right-hand motor skill practice, but no interlimb transfer after left-hand practice. On the other hand, our results show consistent interlimb transfer effects in left-handed subjects, irrespective of whether the dominant left or the non-dominant right arm has been initially trained. In conclusion, our results add to the body of literature by detecting the differences in the magnitude of motor skill acquisition and interlimb transfer between left- and right-handed subjects after short-term unilateral motor skill practice.

  • Yoshiyuki Sugishita, Junko Kurita, Tamie Sugawara, Yasushi Ohkusa
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 39-46
    Published: 2020
    Released on J-STAGE: May 22, 2020
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    In Japan, the reported cases of syphilis have been increasing since 2011 especially in large cities such as Tokyo. The objective of this study was to evaluate the risk of HIV infection for syphilis co-infection on the population of Tokyo, Japan. We analyzed data of syphilis cases obtained from additional surveillance by the Tokyo Metropolitan Government in 2018, including those with human immunodeficiency virus (HIV) infection as well as data of HIV/acquired immunodeficiency syndrome (AIDS) cases during 1985-2017. We calculated the incidence of symptomatic syphilis cases among HIV-infected or non-HIV-infected individuals. Similarly, we calculated the incidence of syphilis, including asymptomatic cases, among each population. The relative risk of HIV infection for syphilis, including or excluding asymptomatic syphilis cases, was estimated. The relative risk was calculated by dividing the incidence of syphilis in the HIV-infected population by that in the non-HIV-infected population. Of the 1,775 syphilis cases reported in 2018, 172 cases were infected with HIV, 575 cases were uninfected, and the remainder were either unknown or not reported. The cumulative number of HIV/AIDS cases during 1985-2017 in Tokyo was 9,629; among them, 172 were co-infected with syphilis. The relative risk of HIV infection for syphilis was estimated as 423.29 if asymptomatic syphilis cases were included, and 372.37 if they were excluded. These results showed an extremely high risk of HIV infection. Since many syphilis cases have unknown or unreported HIV infection status, reduction of these cases might contribute to more reliable estimation of HIV infection risk.

Perspective
  • Carlos A. Delgado, Roberto L. Shimabuku, Pamela M. Chiroque-Solano
    Article type: Perspective
    2020 Volume 251 Issue 1 Pages 47-49
    Published: 2020
    Released on J-STAGE: May 28, 2020
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    The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.

Regular Contribution
  • Masatoshi Mugikura, Yumi Sugawara, Yasutake Tomata, Seiki Kanemura, Ak ...
    Article type: Regular Contribution
    2020 Volume 251 Issue 1 Pages 51-59
    Published: 2020
    Released on J-STAGE: May 28, 2020
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    It is already known that adult height is a factor associated with an increased risk of colon cancer and postmenopausal breast cancer, pancreatic cancer, premenopausal breast cancer, and ovarian cancer. However, the association between adult height and lung cancer incidence remains unclear. The purpose of the present study was to examine the association between adult height and the risk of lung cancer incidence in the Japanese population. We analyzed data for 43,743 men and women who were 40-64 years old at the baseline in 1990. We divided the participants into quintiles based on height at the baseline. Cox proportional hazards analysis was used to estimate the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of lung cancer according to adult height, after adjustment for potential confounders. We identified 1,101 incident case of lung cancer during 24.5 years of follow-up. The multivariate HRs and 95% CIs for the highest category relative to the lowest were 1.48 (1.15-1.91) in men and 1.35 (0.91-1.99) in women. Furthermore, the association between adult height and the incidence of lung cancer was found the significant increased risk among ever smokers in men, but not never smokers. We also observed that adult height tend to be associated with an increased risk of small cell lung cancer and squamous cell carcinoma. This prospective cohort study has demonstrated a positive association between adult height and the risk of lung cancer incidence among men, especially those who have ever smoked.

Case
  • Risa Kojima, Makoto Harada, Akinori Yamaguchi, Koji Hashimoto, Yuji Ka ...
    Article type: Case
    2020 Volume 251 Issue 1 Pages 61-68
    Published: 2020
    Released on J-STAGE: May 29, 2020
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    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis injures small vessels and causes severe systemic organ injury. Main target antigens of ANCA are myeloperoxidase and proteinase 3. ANCA strongly associates with the development and progression of the vasculitis. Its manifestations include rapidly progressive glomerulonephritis, interstitial pneumonitis, alveolar hemorrhage, purpura, and neurological disorder. Most patients with ANCA-associated vasculitis in Japan are elderly and have atherosclerotic risk factors. Cholesterol emboli are systemic vascular inflammation triggered by cholesterol crystals. Cholesterol emboli cause kidney dysfunction and ischemia of the intestines, brain, heart, skin, and peripheral nerves. Diabetes mellitus, hypertension, hyperlipidemia, and history of cardiovascular diseases are risk factors of the development of cholesterol emboli. We report a case of ANCA-associated vasculitis coexisting with cholesterol emboli. A 76-year-old woman was diagnosed with ANCA-associated interstitial pneumonitis. She rapidly developed progressive glomerulonephritis, purpura, and peripheral sensory nerve disorder. A kidney biopsy revealed that renal dysfunction was caused by vasculitis of the interlobular arteries and cholesterol emboli. A skin biopsy revealed that purpura was caused by cholesterol emboli. Glucocorticoid and statin therapies were administered. Thereafter, the renal function and other symptoms improved and stabilized. The representative symptoms of ANCA-associated vasculitis and cholesterol emboli are closely similar, and it is difficult to distinguish between these diseases when they coexist. Because the background characteristics of patients with ANCA-associated vasculitis and risk factors of cholesterol emboli overlap, at the time of diagnosing ANCA-associated vasculitis, clinicians should consider the possibility of cholesterol emboli coexistence.

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