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    大腿四頭筋の等尺性収縮は、膝蓋上外側アプローチによる膝関節内注射の正確性を向上する

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    Background: Intra-articular injection is an important technique for treating rheumatoid arthritis and osteoarthritis of the knee. However, medication is often inaccurately injected outside of the joint. We devised an intra-articular injection method in which the needle is inserted into the suprapatellar bursa while the patient maintains isometric contraction of the quadriceps. This isometric contraction method is based on the concept that isometric contraction of the quadriceps induces contraction of the articularis genus muscle, thus expanding the lumen of the suprapatellar bursa. Methods: Intra-articular injections were performed on 150 osteoarthritic knees without effusion. The knees were alternately assigned to the isometric quadriceps method group (75 knees) and non-activated quadriceps method group (75 knees). Prior to joint injection, the anterior-posterior dimension of each suprapatellar bursa was measured to ascertain its expansion. The isometric quadriceps method was performed with the quadriceps and the articularis genus muscle maintained in a contracted state. The non-activated quadriceps method was performed in a relaxed state. Ultrasound guidance was not used for either method. Subsequently, an ultrasonic probe was used only to confirm whether the intra-articular injections were successful. We compared the accuracy of injections performed between the 2 groups. Results: Suprapatellar expansion was significantly larger (p < 0.001) using the isometric quadriceps method (2.1 ± 1.4 mm [range, 0 to 5 mm]) than using the non-activated quadriceps method (0.8 ± 0.7 mm [range, 0 to 2 mm]). The percentage of accurate intra-articular injections was significantly higher (p = 0.0287) using the isometric quadriceps method (93%) compared with the non-activated quadriceps method (80%). Conclusions: In comparison with the non-activated quadriceps method, the isometric quadriceps method led to a larger expansion of the suprapatellar bursa, which should lead to more accurate intra-articular injections. The isometric quadriceps method is effective in reducing inaccurate injections into the synovium or surrounding fatty tissues. Clinical relevance: Putting force on the quadriceps muscle increases the success rate of intra-articular injection of the knee. The results of this study could provide a clinically relevant injection technique for future treatment.博士(医学)・乙第1448号・令和元年12月5日Copyright © 2018 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

    ヒト多能性幹細胞を用いた脳幹オルガノイドの開発

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    The brainstem is a posterior region of the brain, composed of three parts, midbrain, pons, and medulla oblongata. It is critical in controlling heartbeat, blood pressure, and respiration, all of which are life-sustaining functions, and therefore, damages to or disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders. However, existing organoid models are limited in the extent hPSCs recapitulate human brain development and hence are not able to fully elucidate the diseases affecting various components of the brain such as brainstem. Here, we developed a method to generate human brainstem organoids (hBSOs), containing midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, dopaminergic neurons, and neural crest lineage cells. Single-cell RNA sequence (scRNA-seq) analysis, together with evidence from proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem, which raises the possibility of making use of hBSOs in investigating central nervous system disorders affecting brainstem and in efficient drug screenings.博士(医学)・乙第1479号・令和2年12月24日Copyright © 2020 Eura, Matsui, Luginbühl, Matsubayashi, Nanaura, Shiota, Kinugawa, Iguchi, Kiriyama, Zheng, Kouno, Lan, Kongpracha, Wiriyasermkul, Sakaguchi, Nagata, Komeda, Morikawa, Kitayoshi, Jong, Kobashigawa, Nakanishi, Hasegawa, Saito, Shiromizu, Nishimura, Kasai, Takeda, Kobayashi, Inagaki, Tanaka, Makinodan, Kishimoto, Kuniyasu, Nagamori, Muotri, Shin, Sugie and Mori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

    スエヒロタケ(Schizophyllum commune)によるアレルギー性気管支肺真菌症の一例

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    背景: 今回我々は、糸状菌のスエヒロタケが原因と考えられるアレルギー性気管支肺真菌症(alergic bronchopulmonary mycosis,ABPM)を経験したので報告する。症例: 70代、女性。一か月前から咳・喀痰があり、胸部レントゲンにより右上葉無気肺を疑われた。胸部CTでは右上葉浸潤影とともに、粘液栓あるいは腫瘍によると思われる気道内閉塞が指摘された。気管支鏡により閉塞部位の黄色粘液栓が吸引除去され、細菌検査、細胞診に提出された。細胞診では、多数の好酸球とシャルコーライデン結晶を背景に、アスペルギルスと形態的に類似する糸状の菌糸を認め、培養検査と遺伝子解析により、同糸状菌はスエヒロタケと同定された。また、悪性像はみられなかった。治療が開始され一時は改善したが、約二年後には好酸球数の上昇と胸部レントゲンで浸潤影がみられ再発している。結論: ABPMの原因真菌はアスペルギルスが多いが、近年、スエヒロタケも増加している。原因菌によって抗真菌剤が異なるため、その同定は極めて重要である。原因菌の特定と治療方針の決定に細胞診による形態的考察が貢献できると考える

    マウス味蕾における癌胎児抗原5T4の発現

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    Background: Multicellular taste buds located within taste papillae on the tongue mediate taste sensation. In taste papillae, taste bud cells (TBCs), such as taste receptor cells and taste precursor cells, and the surrounding lingual epithelium including epithelial progenitors (also called taste stem/progenitor cells) are maintained by continuous cell turnover throughout life. However, it remains unknown how the cells constituting taste buds proliferate and differentiate to maintain taste bud tissue. Based on in situ hybridization (ISH) screening, we demonstrated that the oncofetal antigen 5T4 (also known as trophoblast glycoprotein: TPBG) gene is expressed in the adult mouse tongue. Results: In immunohistochemistry of coronal tongue sections, 5T4 protein was detected at a low level exclusively in the basal part of the lingual epithelium in developing and adult mice, and at a high level particularly in foliate papillae and circumvallate papillae (CVPs). Furthermore, immunohistochemistry of the basal part of CVPs indicated that the proliferation marker PCNA (proliferating cell nuclear antigen) co-localized with 5T4. 5T4 was strongly expressed in Krt5+ epithelial progenitors and Shh+ taste precursor cells, but weakly in mature taste receptor cells. The number of proliferating cells in the CVP was higher in 5T4-knockout mice than in wild-type (WT) mice, while neither cell differentiation nor the size of taste buds differed between these two groups of mice. Notably, X-ray irradiation enhanced cell proliferation more in 5T4-knockout mice than in WT mice. Conclusion: Our results suggest that 5T4, expressed in epithelial progenitors (taste stem/progenitor cells), and taste precursor cells, may influence the maintenance of taste papillae under both normal and injury conditions.博士(医学)・甲第731号・令和2年3月16日Copyright © 2019 Takahashi, Takahashi, Stern, Kirita and Tsuboi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

    日本における非代償性急性心不全患者の30日および90日以内の心不全再入院の発生率と臨床的意義 : NARA-HF研究より

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    Background: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. Conclusions: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.博士(医学)・甲第735号・令和2年3月16日日本循環器学会の許諾を得て登録(2020年9月2日付)ジャーナル公式サイト(日本循環器学会HP内):https://www.j-circ.or.jp/journal/公開サイト(J-STAGE):https://www.jstage.jst.go.jp/browse/circj

    尿中Nerve Growth Factorは、過活動膀胱症状を呈する患児の治療効果の予測因子になる

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    Objective: To assess urinary nerve growth factor (NGF) in children with overactive bladder (OAB) and to investigate the relationship between urinary NGF/creatinine (Cr) levels and OAB. Patients and methods: Thirty-five children (27 boys and 8 girls) with OAB and 11 children (6 boys and 5 girls) without OAB or any other urinary symptoms, who served as controls, were included in this study. Urinary NGF levels were measured using enzyme-linked immunosorbent assay. The total urinary NGF levels were adjusted with the concentration of urinary creatinine (NGF/Cr level). Refractory OAB was defined as little improvement in OAB symptoms despite at least 3 months of urotherapy and anticholinergic agent treatment. Urinary NGF/Cr was compared between the children with OAB and the controls. The relationship between urinary NGF/Cr and treatment outcomes was also evaluated. Results: Urinary NGF/Cr was significantly higher in the children with OAB when compared with those in the control group (0.65 ± 0.82 vs 0.11 ± 0.09, P = .0007). Improvement of OAB symptoms was observed in 26 out of 35 children (74%). The remaining 9 children showed refractory OAB symptoms (the refractory group). Urinary NGF/Cr was significantly higher in the refractory group than in the improved group (1.28 ± 1.34 vs 0.44 ± 0.39, P = .027). Conclusion: Urinary NGF/Cr was significantly higher in the children with OAB than in the controls, and was significantly higher in the refractory group than in the improved group. Urinary NGF/Cr could not only be a potential biomarker for children with OAB, but also a predictor of therapeutic efficacy in children with OAB.博士(医学)・乙第1454号・令和2年3月16日Copyright © 2017 Elsevier Inc. All rights reserved

    下部直腸癌におけるMRIを用いた歯状線浸潤の診断精度

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    Purpose: To retrospectively assess the accuracy of magnetic resonance imaging (MRI) in predicting dentate line invasion in low rectal cancer. Materials and methods: Eighty-one patients with primary rectal cancer were assessed by dynamic contrast-enhanced MRI. The location of the dentate line was assessed on MRI in 27 patients with upper-mid rectal cancer. Two observers independently evaluated the distance between the distal tumor edge and the MRI-defined dentate line in 54 patients with low rectal cancer, and the imaging and histological findings were compared. Results: The MRI-defined dentate line was 24.0 ± 3.8 mm above the anal verge in patients with upper-mid rectal cancer. The dentate line invasion status agreed with the histological findings in 49/54 (91%) patients (κ = 0.72 [95% CI 0.50-0.95]) for observer 1, and in 51/54 (94%) patients (κ = 0.83 [0.65-1.00]) for observer 2 in patients with low rectal cancer. Interobserver agreement was good (κ = 0.83 [0.65-1.00]). The MRI-derived distance between the distal tumor edge and the dentate line had significant correlation with the histological distance (r = 0.86 for reader 1 and 0.75 for observer 2). Conclusion: MRI demonstrates high accuracy in predicting dentate line invasion in low rectal cancer.博士(医学)・甲第748号・令和2年6月30日© Japan Radiological Society 2020© 2020 Springer Nature Switzerland AG. Part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in Japanese journal of radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11604-020-00933-5

    災害発生時における精神保健医療と災害派遣精神医療チーム(DPAT)

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