Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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

PURPOSE: The incidence of femoral localized periosteal thickening (LPT), which can precede atypical femoral fracture (AFF), is not low (1-10%) in Japanese patients with autoimmune inflammatory rheumatic diseases (AIRDs). We explored the associations between underlying AIRDs and the prevalence of LPT. METHODS: We conducted post-hoc analyses of two cohorts that included a total of 280 Japanese women, 105 of whom had AIRDs and had been taking bisphosphonate (BP) and prednisolone (PSL), and 175 of whom had rheumatoid arthritis (RA). RESULTS: LPT was detected in a total of 18 patients (6.4%) and three (1.1%) developed AFFs. RA was negatively correlated with LPT. A disease other than RA requiring glucocorticoid treatment, BP use ≥ 5 years, PSL use ≥ 7 years, and a PSL dose ≥ 5.5 mg/day were positively correlated with LPT. After adjusting for age, diabetes mellitus, and BP duration or daily PSL dose, RA was no longer associated with LPT. CONCLUSION: LPT in Japanese patients with AIRDs was associated with BP and glucocorticoid treatment rather than underlying AIRDs. When a PSL dose ≥ 5.5 mg/day is required long-term (typically combined with long-term BP treatment [≥ 5 years]), clinicians need to pay particular attention in case LPT and AFF, as well as glucocorticoid-induced osteoporosis.

DOI： 10.1093/mr/roac062

PubMed

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：中部リウマチ学会  

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Language：Japanese   Publisher：中部リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：中部リウマチ学会  

サルコペニアチェック検査を実施された関節リウマチ(RA)患者について、その結果とRAの疾患活動性や治療について分析した。当科外来でサルコペニアチェック検査を受けた65歳以上のRA患者20例(男性5例、女性15例、中央値75.5歳)を対象とした。サルコペニアは7例(35%)で全例女性、フレイルの4例(20%)は全例サルコペニアに該当し、4例中2例は重症サルコペニアで、サルコペニアとフレイルは関連していた。サルコペニア・フレイルに関する因子として、身体活動量とたんぱく質摂取量に有意差はなかったが、サルコペニア群では食事摂取量の低下が示唆された。骨粗鬆症については骨粗鬆症性骨折リスク評価で10年以内における骨粗鬆症性骨折・大腿骨近位部骨折リスクが15%以上の頻度はサルコペニア群の方が非サルコペニア群より有意に多く認められ、女性のみで比較しても骨粗鬆症性骨折リスクが15%以上の頻度はサルコペニア群で高かった。

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

INTRODUCTION: Femoral localized periosteal thickening (LPT, also termed "beaking") of the lateral cortex often precedes an atypical femoral fracture (AFF). Bisphosphonate (BP) use, glucocorticoid use, and Asian race are major risk factors for developing such fractures. The aim of this study was to determine whether the trabecular bone score (TBS) reflecting the lumbar trabecular microarchitecture was related to LPT in glucocorticoid-treated Japanese patients with autoimmune diseases. MATERIALS AND METHODS: We retrospectively investigated 111 women with autoimmune diseases treated with prednisolone (PSL) who had undergone both femoral X-ray and dual-energy X-ray absorptiometry of the L1 - L4 lumbar vertebrae and for whom TBS could be evaluated for two or more of these. RESULTS: Femoral LPT was evident in the X-rays of 18 of 111 patients (16.2%). Higher body mass index (BMI), longer duration of PSL use and longer duration of BP use were significant in patients with LPT compared to those without. The TBS was significantly lower in patients with LPT than in those without (1.314 ± 0.092 vs. 1.365 ± 0.100, p = 0.044); however, the lumbar bone mineral density did not differ significantly (0.892 ± 0.141 vs. 0.897 ± 0.154 g/cm2, p = 0.897). TBS was significantly associated with LPT (odds ratio, 0.004; 95% CI, 0 - 0.96; p = 0.048), but not in the multivariate analysis including BMI, duration of PSL use and duration of BP use. CONCLUSIONS: The TBS was lower in glucocorticoid-treated Japanese women with autoimmune diseases with LPT than in those without LPT, and deteriorated trabecular microarchitecture influenced by longer use of BP and glucocorticoid might be associated with the development of LPT.

DOI： 10.1007/s00774-021-01244-z

PubMed

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Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

B型肝炎ワクチンは本邦では2種類が使用可能であり、本学では製剤Aのワクチンを使用していた。2016年の熊本地震により製剤Aの供給がなくなったことから一時的に製剤Bに変更した。本研究は、B型肝炎ワクチンの種類による抗体陽転化率と接種後抗体価の違いを明らかにすることを目的とした。2014年度から2019年度に本学でB型肝炎ワクチン接種と血液抗体検査を実施された医学部・歯学部の学生について後ろ向きに検討した。2016年度1シリーズ3回のうちの2回目から2017年度3回目まで製剤Bのワクチンを使用し、それ以外は製剤Aのワクチンを使用していた。抗体陽転化率は製剤Bを使用した2016年度と2017年度は83%、84%で、すべて製剤Aを使用した年度の95%以上と比較して低かった(p<0.001)。接種後抗体価も、製剤Bを使用した2016年度、2017年度はすべて製剤Aを使用したいずれの年度より低かった(p<0.001)。B型肝炎ワクチンの種類により抗体陽転化率およびワクチン接種後の抗体価に差があることが明らかになった。2020年12月時点で製剤Bは製法変更により本研究で使用したワクチンより免疫原性が改善されている。より高い有効性を得るために製剤によっては皮下注射から筋肉内注射に変更することも考慮される。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J02903&link_issn=&doc_id=20211221420025&doc_link_id=10.57540%2Fcampushealth.58.2_155&url=https%3A%2F%2Fdoi.org%2F10.57540%2Fcampushealth.58.2_155&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本臨床リウマチ学会  

関節リウマチ(RA)患者の高齢化は若年発症RA患者の高齢化に加え、高齢発症の患者も増加している。我々は1991年のRA429症例と2018年のRA368例について横断的検討を行い年齢、性比を検討した。その結果1991年の平均年齢は55.3歳でRA患者のピークは50歳代と60歳代にあり、2018年の平均年齢は66.9歳で、70歳代にピークが認められ(P=0.000)、高齢化が確認された。性別の検討では2018年は1991年に比べて男性患者の増加が認められた(P=0.003)。2018年のRA症例の検討では、65歳以上で発症した高齢発症RA(EORA)では初発関節として大関節の割合多く65歳未満の若年発症RA(YORA)では小関節の発症が多かった(P<0.01)。RFはYORAが73.1%、EORAが60.7%(P=0.02)、抗CCP抗体はYORAが68.4%、EORAが58.3%(P=0.034)とRFと抗CCP抗体共にYORAで陽性率が高かった。治療ではMTXの使用頻度、量ともYORAが多く使用されていた。アミロイドーシスは全体の1.6%に存在し、全例がYORAで解析時に65歳以上であった。(著者抄録)

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：新潟県医師会  

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00198-020-05601-y

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Other Link： http://link.springer.com/article/10.1007/s00198-020-05601-y/fulltext.html

Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

<sec><title>Objectives</title> Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients.

</sec><sec><title>Methods</title> Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate &lt; 60 mL/min/1.73 m² for &gt; 3 months.

</sec><sec><title>Results</title> Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P.

</sec><sec><title>Conclusion</title> Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

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DOI： 10.1177/0961203320983906

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/0961203320983906

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41598-020-66945-3

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Other Link： http://www.nature.com/articles/s41598-020-66945-3

Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：English  

We report three rheumatoid arthritis (RA) patients with false-positive procalcitonin (PCT) based on semiquantitative immunochromatography assays without infection, but who had negative PCT assay results based on quantitative methods. Immunochromatography was useful for screening; however, other heterophilic antibodies rather than rheumatoid factor were possible to affect, especially in RA flare.

DOI： 10.1002/ccr3.2968

PubMed

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Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：中部リウマチ学会  

1991年の関節リウマチ429例と2018年の関節リウマチ368例を対象に、年齢や性を比較した。その結果、2018年に70歳代が4倍、80歳以上が15倍に増加し、男性が有意に増加していた。次に、2018年の368例の腎機能障害を調査した。65歳以上発症108例(A群)、65歳未満発症260例(B群)に分類し、更にB群で65歳未満発症で65歳以上の症例129例(C群)を抽出し、3群間で腎機能を比較した。その結果、発症時の血算や血清Cr、尿異常(血尿、蛋白尿等)は3群間に差がなかった。eGFR、抗CCP抗体はB群がA群、C群より有意に高かった。RFはB群がA群より有意に高かったが、力価に差はなかった。AAアミロイドーシスを全体の1.6%に認め、全例がC群であり、C群の4.7%を占めた。治療はステロイドの使用頻度、量ともに3群間に差はなかったが、メトトレキサートとbDMARDsの使用頻度、量はB群がA群、C群より有意に多かった。

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

本学では、インフルエンザを自己申告した学生全員に「インフルエンザ確認票」を用いて状況確認と保健指導を行っている。今回、2016〜2018年度の罹患者568名のインフルエンザ確認票から、各年度の「罹患者数」「発生状況」「罹患者の学部・学年」「治療に使用された薬剤」などについて調査した。各年度の罹患者数は2016年136名、2017年156名、2018年273名であり、2018年度が多かった。発生状況はいずれの年度も1月の第2〜3週に急増したのち漸減し、5〜6月まで散見された。学部別にみた罹患者割合は医学部が最も高く、次いで歯学部、工学部の順であった。学年別にみた罹患者割合は2年次が最も高く、次いで1年次、3年次の順であった。使用薬剤のうち吸入薬(ザナミビル、ラニナミビル)の使用率は2016年度52.2%、2017年度63.5%、2108年度37.3%と2018年度に減少し、2018年度には代わってバロキサビルマルボキシルが増え26.1%を占めていた。

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Language：Japanese   Publisher：新潟医学会  

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DOI： 10.1007/s00296-019-04407-4

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00990&link_issn=&doc_id=20200819040006&doc_link_id=%2Fdg3nigta%2F2019%2Fs13309%2F001%2F0349-0349%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2019%2Fs13309%2F001%2F0349-0349%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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Language：Japanese   Publisher：(NPO)日本臨床運動療法学会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

本学では「医療関係者のためのワクチンガイドライン第2版」に準じて麻疹・風疹・水痘・流行性耳下腺炎の抗体価測定およびワクチン接種を行っている。抗体価のみでワクチン1回接種者を、かつ接種後抗体価と予防接種歴で2回目接種者を選定する方法(2段階法)から、平成29年より抗体価と接種歴で接種者および回数を選定するより簡素な方法(1段階法)に変更した。両選定法と抗体獲得率について、後ろ向き横断的に検討した。2段階法378人中、抗体価が基準値以上は麻疹38%(うち接種歴2回あり72%)、風疹55%(60%)、水痘82%(0.3%)、流行性耳下腺炎42%(1%)であった。1回ワクチン接種を行い、基準値以上になったのは麻疹35%、風疹77%、水痘84%、流行性耳下腺炎69%であり、そのうち接種歴2回未満の者に2回目接種を行った(のべ46人)。1段階法377人中、1回目接種者数は前年と同等で、2回目接種者はのべ37人に減少した。最終抗体獲得率は麻疹59%、風疹94%、水痘98%、流行性耳下腺炎90%であった。ワクチン接種後に有意な抗体増加を認めた割合は、麻疹において低かった。1段階法は業務の負担が軽減され、最終抗体獲得率も麻疹以外では良好であった。麻疹はワクチン接種を行っても基準値以上の抗体価に達する割合は低く、現在でも流行が散発する麻疹の感染者の抗体価も踏まえてさらに検討する必要がある。(著者抄録)

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DOI： 10.1002/ccr3.2102

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：中部リウマチ学会  

当院で経験した80歳以上の高齢RA(関節リウマチ)合併アミロイドーシス3例(症例1:82歳、症例2:81歳、症例3:85歳、全例女性)について検討した。いずれの症例も感染症の発症リスクを下げることを目的にSAA(血清アミロイド-シスA蛋白)の測定結果を参考にして、生物学的製剤であるエタネルセプト(ETA) の使用間隔を延長し調整した。その結果、ETAの使用により全例で重症感染症は発症せず、生命予後の改善が得られた。

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

本学(大学)保健管理センターでは平成18年度より学生定期健康診断の際に、全学部の学生と大学院生を対象にメンタルヘルス検診を実施してきたが、質問数が42問と多く学生の負担になる、検診表の印刷費やデータ入力のための外注費がかさむなどの理由から、30年度より精神健康状態を少ない質問数(6問)で測定できるKessler6(K6)を用いたタブレットによるメンタルヘルス検診を開始しており、今回、学生を対象にしたメンタルヘルス検診におけるK6の信頼性を検討するとともに、30年度の検診結果10467名(大学生9096名、大学院生1371名)を検討した。その結果、K6の信頼性については、信頼性の指標であるクロンバックのα係数は0.87と、「信頼性あり」とされる0.8以上であったことから、K6は学生のメンタルヘルス検診でも十分な信頼性があると考えられた。また、本学の学生の精神健康状態は比較的良好で、分布も標準的であった。

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

本学(大学)では、学生・職員の健康増進の一環として、2017年度からロコモティブ・シンドローム(ロコモ)、サルコペニア予防のための任意の身体計測(健康チェック)を行っており、今回、希望した職員118名(男性28名、女性90名、25〜73歳、教員14名、その他の職員104名)に対して実施した初年度(2017年度)の結果について報告した。その結果、有所見者はロコモが44名(38%)で、サルコペニアは認められなかったが、握力で1名(0.8%)、四肢筋量で18名(15%)が基準値に満たなかった。ロコモとサルコペニア両者に密接に関係する骨量の有所見者は、要精検19名(16%)、要指導27名(23%)であった。ロコモと骨量は50歳以上で有所見率が増加する傾向がみられ、ロコモ、四肢筋量、骨量とも該当者は女性に多かった。

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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DOI： 10.1080/13506129.2019.1582512

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DOI： 10.1016/j.cca.2018.10.022

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00990&link_issn=&doc_id=20200130080004&doc_link_id=%2Fdg3nigta%2F2018%2Fs13211%2F001%2F0397-0397%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2018%2Fs13211%2F001%2F0397-0397%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00990&link_issn=&doc_id=20190531080006&doc_link_id=%2Fdg3nigta%2F2018%2Fs13207%2F001%2F0281-0281%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2018%2Fs13207%2F001%2F0281-0281%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

DOI： 10.1007/s10157-017-1491-9

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

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Language：Japanese   Publisher：中部リウマチ学会  

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00990&link_issn=&doc_id=20180328050011&doc_link_id=%2Fdg3nigta%2F2017%2Fs13110%2F001%2F0617-0617%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2017%2Fs13110%2F001%2F0617-0617%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer London  

Summary: Once a localized reaction (beaking) was detected, discontinuation of bisphosphonates (BPs) and switching to vitamin D supplementation or teriparatide therapy effectively improved its shape. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete atypical femoral fracture increased and consideration of prophylactic fixation for such patients was required. Introduction: Femoral localized reaction (localized periosteal thickening of the lateral cortex, beaking) is reported to precede atypical femoral fractures (AFFs) and to develop in 8–10% of patients with autoimmune diseases taking BPs and glucocorticoids. The aims of the present study were to retrospectively investigate the shapes of localized reaction to consider how to manage the condition. Methods: Twenty femora of 12 patients with autoimmune diseases who were on BPs and glucocorticoids exhibited femoral localized reaction. The heights of localized reaction were measured and the shapes classified as pointed, arched, and other. Localized reaction changes were divided into three categories: deterioration, no change, and improvement. A severe form of localized reaction was defined
this was associated with prodromal pain, de novo complete AFF, or incomplete AFF with a fracture line at the localized reaction. Results: The mean height of localized reaction was 2.3 ± 0.8 mm (range, 1.0–3.7 mm) and the pointed type was 35%. Localized reaction was significantly higher (3.3 ± 0.8 vs. 2.1 ± 0.7 mm
p = 0.003) and the pointed type more common (78 vs. 27%
p = 0.035) in those with the severe form of localized reaction. Seven patients with localized reactions discontinued BPs just after localized reaction was detected, but five continued on BPs for 2 years. Localized reaction deterioration was more common in patients who continued than discontinued BPs (100 vs. 29%
p = 0.027). After 2 years, all patients had discontinued BPs and localized reaction did not deteriorate further in any patient. Conclusions: Once a localized reaction was detected, discontinuation of BPs and switching to vitamin D supplementation or teriparatide therapy effectively improved it. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete AFF increased and consideration of prophylactic fixation for such patients was required.

DOI： 10.1007/s00198-017-4038-8

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Language：English   Publisher：TAYLOR & FRANCIS LTD  

DOI： 10.1080/13506129.2017.1291421

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PubMed

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：中部リウマチ学会  

27歳女。13歳時に両手関節、手指の疼痛、腫脹が出現し若年性特発性関節炎(JIA)と診断され、PSL、メトトレキサート(MTX)等で治療されていた。今回、小児科から内科への移行のため当科を紹介受診した。MTXを8mg/週に増量したが、低疾患活動性から中疾患活動性で推移していた。また、右手関節は職業上酷使されるため疼痛、腫脹が強く、レントゲン上も骨破壊が認められたため、年齢、職業、将来の挙児希望、骨破壊の程度を勘案しInfliximab 200mgを開始した。開始5ヵ月後に腫脹が消失し、その後疼痛も消失した。2年間は8週おきに継続し寛解状態を維持していたが、嘔気が出現しMTXの副作用と考えられたため6mg/週に減量した。寛解状態が続いていたためInfliximabは10週間隔に延長し、その後12週間隔に延長したもののMTXによる嘔気が強く、MTXを含む全ての経口薬を中止しInfliximabも中止した。Loadingを行わずセルトリズマブ・ペゴルにスイッチし徐々に間隔を延長し、以後も寛解が維持されていたため中止とした。なお、右手関節の骨病変には軽度の修復が認められた。

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症例1:58歳女。47歳時に甲状腺乳頭癌に対し甲状腺全摘出術を施行されていた。今回、食欲不振、倦怠感のため入院となり、入院時から腰痛があり、腰椎圧迫骨折と診断された。ビスホスホネート製剤は剤型や内服方法の問題で自己中断しており、デノスマブ60mg皮下注射を行い、アルファカルシドール1μgをエルデカルシトール0.75μgに変更した。注射6日後に補正血清カルシウムが6.3mg/dLに低下し、経口および点滴で補充を行い改善した。症例2:67歳女。65歳時にIV型進行胃癌に対し胃全摘術を施行されていた。今回、骨密度低下を指摘され、胃全摘術後から嘔気が続いていたことからビスホスホネート製剤ではなくデノスマブ60mg皮下注射を行い、アルファカルシドール0.5μgと乳酸カルシウム2gを併用した。下肢蜂窩織炎および食欲不振のため注射後32日目に入院した際、補正血清カルシウム値が7.5mg/dLと低下しており、点滴で補充を行い改善した。

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues.
A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log(10)%amyloid). The results of sex-, age-, and Log(10)%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group.
There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

DOI： 10.1080/13506129.2017.1338565

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

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder that generally occurs in children and predominantly affects the long bones with marginal sclerosis. We herein report two cases of adult-onset CRMO involving the tibial diaphysis bilaterally, accompanied by polyarthritis. Magnetic resonance imaging (MRI) showed both tibial osteomyelitis and high intensity of the extensive lower leg muscles. Anti-interleukin-6 therapy with tocilizumab (TCZ) effectively controlled symptoms and inflammatory markers in both patients. High intensity of the lower leg muscles detected by MRI also improved. These cases demonstrate that CRMO should be included in the differential diagnosis of adult patients with bone pain, inflammation, and high intensity of the muscles detected by MRI. TCZ may therefore be an effective therapy for muscle inflammation of CRMO.

DOI： 10.2169/internalmedicine.8473-16

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(公社)全国大学保健管理協会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：中部リウマチ学会  

60歳男。鼠径部の腫瘤の精査・加療を主訴とした。20年前に関節リウマチ(RA)と診断され、メソトレキサート(MTX)開始から約4年に左鼠径部の腫瘤と左下肢の浮腫が出現した。入院時検査では軽度の貧血、肝機能上昇、炎症反応の著増とsIL-2レセプターの上昇を認め、リンパ節生検の結果はdiffuse large B-cell lymphomaであり、EBウイルスは既感染パターンであったが、組織のin situ hybridizationは陰性であった。悪性リンパ腫の診断でR-CHOPを行い、治療後にRAが増悪したため、MTXは使用せずB細胞に影響を与えない生物学的製剤を導入したが、感染症を繰り返し発症した。

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73歳女。息切れ、咳嗽を主訴とした。右頸部リンパ節結核の既往があり、関節リウマチ(RA)に対しメトトレキサート、エタネルセプト(25mg/週)にて加療中であった。感冒症状にて受診し、胸部レントゲンで両側中下肺野に軽度のスリガラス様陰影を認めた。入院時検査ではβ-Dグルカンの上昇を認めたが、気管支肺胞洗浄液中に有意菌や結核菌は検出されず、PCR法にてPneumocystis jiroveciiが検出された。胸部CTでは右中葉の地図状スリガラス様濃度の上昇と下葉の牽引性気管支拡張を伴う構造変化が観察された。ニューモシスチス肺炎と診断して集学的治療を開始したが、急激に間質性肺炎が増悪して低酸素血症と肺の構造変化が進行し、第25病日に死亡した。

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DOI： 10.1186/s13104-016-2052-0

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER LONDON LTD  

A Summary The incidence of beaking, which has been reported to precede atypical femoral fracture, was high and increased over 2 years in patients with autoimmune diseases who were taking bisphosphonates and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking, and bisphosphonate drug holidays should be considered.
Introduction Atypical femoral fractures (AFFs) have been recently recognized as complications associated with bisphosphonate (BP) use. AFFs are considered to be stress fractures; localized periosteal thickening of the lateral cortex is often present at the fracture site; this thickening is termed "beaking." Beaking has been reported to precede AFF. The aims of the present study were to evaluate the incidence of latent beaking in patients with autoimmune diseases taking BPs and glucocorticoids and to identify risk factors for beaking.
Methods A total of 125 patients with autoimmune diseases who were taking BPs and glucocorticoids was included; 116 patients underwent X-rays and analysis of serum and urine bone metabolic markers annually for 2 years. Mean patient age was 54.5 years; there were 105 (90.5 %) females and the mean duration of disease was 13.2 years. Focal lateral cortical thickening in femoral X-rays was defined as beaking.
Results Beaking was detected in 15 femora of 10 patients (8.0 %) at the time of recruitment. Over the 2-year observation period, the incidence of beaking increased to 21 femora of 12 patients (10.3 %), and a complete AFF at the location of beaking occurred in one patient. Beaking was associated with a longer duration of BP treatment (6.1 +/- 1.0 years vs. 5.0 +/- 2.9 years, p = 0.01). Age 40-60 years, BP therapy &gt;= 4 years, and diabetes mellitus were significantly associated with beaking.
Conclusions The incidence of beaking was high, and increased over 2 years, in patients with autoimmune diseases who were taking BPs and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking. Long-term BP/glucocorticoid use was a risk factor for beaking in patients with autoimmune diseases; BP drug holidays should be considered.

DOI： 10.1007/s00198-015-3382-9

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Language：Japanese   Publisher：(一社)日本内科学会  

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Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by periarticular and systemic osteoporosis. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes, circulates to the kidneys and regulates bone metabolism. We herein assessed serum FGF23 and its relationship to inflammation and osteoporosis in patients with RA. Methods Sixty-one patients with RA were included. Serum concentrations of FGF23 were determined using a sandwich enzyme-linked immunosorbent assay. Results The mean (± standard deviation) serum FGF23 concentration was 34.9±9.2 (range, 21.0-61.0) pg/mL. The serum FGF23 level was significantly and positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, disease activity score-28 based on the ESR (DAS-28 ESR) and DAS-28 CRP (r=0.261, p=0.044, r=0.280, p=0.029, r=0.409, p=0.001 and r=0.421, p=0.001, respectively). The serum matrix metalloproteinase-3 level was also significantly and positively correlated with the serum FGF23 level (r=0.331, p=0.015). Concentrations of type I collagen cross-linked N-telopeptide in the serum was significantly correlated with the serum FGF23 level (r=0.272, p=0.034). Neither the bone mineral density in the femoral neck nor lumbar was significantly correlated with the serum FGF23 level. Serum phosphate, calcium, 25-hydroxy vitamin D, and intact parathyroid hormone were not related to the serum FGF23 level. Conclusion In patients with RA, serum FGF23 is correlated with inflammation, the disease activity of RA, and bone absorption markers. Serum FGF23 may be associated with abnormal bone absorption related to RA inflammation. Further studies are necessary to clarify the mechanism underlying this association.

DOI： 10.2169/internalmedicine.55.5507

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Language：English   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). </p><p><b>Methods </b>Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. </p><p><b>Results </b>Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). </p><p><b>Conclusion </b>Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis. </p>

DOI： 10.2169/internalmedicine.55.6941

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The purpose of this study was to clarify the factors related to silent osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Seventy-eight patients with SLE were selected on the basis of having been newly diagnosed and requiring high-dose prednisolone, including pulse therapy with methylprednisolone, as the initial treatment. All the patients initially underwent MRI at 3 months after the start of corticosteroid treatment to detect any early changes in the femoral head. These examinations were then performed again 3 months later. Laboratory parameters were evaluated at the start of steroid treatment and at 1 month thereafter. By 3 months after the start of corticosteroid treatment, silent ONFH was diagnosed by MRI in 21 patients (26.9 %), being bilateral in 11 patients and unilateral in 10. The occurrence of silent ONFH was not related to SLE disease activity index, serological activity, or renal function; it was also unrelated to body mass index (BMI), body surface area (BSA), and the initial dose of prednisolone per unit body weight. However, the total cholesterol level at 4 weeks after the start of steroid treatment tended to be higher in patients with silent ONFH. Patients with a higher triglyceride level showed a significantly higher frequency of silent ONFH both before (p = 0.002) and 4 weeks after (p = 0.036) steroid initiation.A high triglyceride level is an important risk factor for silent ONFH in patients with SLE, and large-scale epidemiologic surveys of such early events are needed in this patient population.

DOI： 10.1007/s10067-015-3075-y

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45歳女性。長女が伝染性紅斑に感染してから6日後、悪寒を伴う発熱に続き、翌日には肉眼的血尿、嘔吐、食欲低下が出現して近医を受診、血小板の著明な減少を指摘され、著者らの施設に紹介となった。所見では貧血や著明な血小板減少、網赤血球の低下、肝機能障害ほか、LDHの高値、軽度腎機能障害、尿蛋白、尿潜血などがみられ、更に心エコーでは全周性に少量の心嚢水を、また眼科検査では両乾性結膜炎と眼底に軟性白斑が認められた。入院当日、血漿交換を試みたが、悪寒戦慄を伴う全身尋麻疹と嘔吐が出現し、FFP製剤に対するアレルギーと診断、治療を中止した。一方、骨髄穿刺検査ではdry tapで、わずかに得られた検体より骨髄の低形成が認められ、再生不良性貧血または骨髄異形成症候群が疑われた。だが、確定診断には至らなかった。以後、血漿交換を中止すると、ADAMTS13活性の著明な減少と抗ADAMTS13抗体陽性所見が持続したため、二重濾過血漿交換療法(DFPP)を併用しながらメチルプレドニゾロン(1000mg/日)によるパルス療法を開始した。その結果、血小板値の回復、LDH低下、ADAMTS13活性の上昇と抗体の陰性化を認め、DFPP中止後も血小板は維持され、ステロイドを漸減した。尚、本症例は血液疾患を背景とした自己免疫反応とパルボウイルスB19感染に伴う免疫反応の関与が考えられた。

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41歳女性。両手指の関節痛と浮腫を自覚し近医を受診、肝機能障害、抗核抗体2560倍、汎血球減少を指摘され、また慢性甲状腺炎と診断され治療を開始した。しかし1ヵ月後、特に誘因なく全身に皮疹が出現し著者らの施設を受診、顔面の紅斑、関節炎、蛋白尿、汎血球減少ほか、抗核抗体および抗ds-DNA抗体陽性から全身性エリテマトーデス(SLE)と診断され、入院となった。所見では汎血球減少や著明な肝機能障害、更に直接ビリルビン、CRPの軽度上昇に加え、血清補体価の低下、抗核抗体陽性、抗ds-DNA抗体やC1q結合免疫複合体の上昇を認め、SLEの疾患活動性が高いことが判明した。また、抗SS-A抗体陽性、APTT延長が認められ、あわせて抗カルジオリピンIgG抗体と抗CL-β2GPI抗体複合体も陽性であった。一方、胸腹部CTでは著明な肝脾腫がみられ、眼底検査では両側眼底に綿花様白斑を多数認め、シルマー試験も両眼陽性であった。以上、このことからシェーグレン症候群と診断されたが、高熱、汎血球減少の進行、高フェリチン血症の出現から血球貪食症候群の合併が疑われた。そこで、メチルプレドニゾロン(mPSL)を1g/日でステロイドパルス療法を1コース施行後、後療法としてmPSLの500mg/日3日間、250mg/日3日間を継続した。その結果、以後、患者はPSL 50mg/日で維持し、シクロスポリン100mg/日の追加により症状は改善、抗ds-DNA抗体も低下傾向となった。

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33歳女性。全身性エリテマトーデス(SLE)と診断後、ステロイド治療を開始するも治療抵抗性であり、アザチオプリン、ミゾリビン(MZR)、タクロリムス(Tac)、メトトレキサート(MTX)などが併用された。だが、便秘の訴えほか、プレドニゾロン(PSL)の20mg/日以下への減量が困難な状態が続いていた。今回、PSL(17.5mg/日)+MTX(10mg/週)+MZR(150mg/日)の服用下で関節痛、発熱、顔面紅斑が出現、加えて抗ds-DNA抗体の上昇がみられた。そこで、PSLを30mg/日に増量し、MZRはTac 3mg/日に変更したが、腹部膨満感を自覚、腹部骨盤CTを行なったところ、腸管気腫症(PCI)と診断され、精査加療目的で著者らの施設へ紹介となった。入院時、検査所見ではリンパ球数の低下、LDLコレステロールの軽度上昇、更に軽度の補体血症が認められ、抗ds-DNA抗体はやや高値であった。対処として連日、高圧酸素療法を行い、低残渣食、ドキシサイクリンの内服、便通コントロールなどの保存療法を行なった結果、症状はX線像上でも改善が確認された。尚、本症例はステロイド治療抵抗性で頻回に再燃を繰り返しており、現時点でも血清学的に疾患活動性が比較的高い状態であり、引き続きPCIについても慎重な経過観察を要するものと考えられた。

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Language：Japanese   Publisher：中部リウマチ学会  

全身性エリテマトーデス(SLE)77症例(男性8例、女性69例)を対象に高脂血症治療薬による特発性大腿骨頭壊死症(ION)発生の有無について検討した。ステロイド治療前および最終診療時にMRIで確認し、ステロイド性ION発生の関連について患者背景、疾患活動性、脂質検査から調べた。その結果、1)77例中21例にIONの発生が認められた。だが、年齢や性別、プレドニゾロン(PSL)初期量、抗リン脂質抗体の有無、ステロイドパルス療法の有無、常習飲酒の有無においてION発生に差は認められなかった。2)一部症例でPSL開始時よりストロングスタチン(アトルバスタチン、ピタバスタチン、ロスバスタチン)が使用されたが、IONの発生に差は認められなかった。但し、IONの発生には喫煙者に多い傾向がみられた。3)SLEの疾患活動性とION発生の有無ではC3、C4、CH50、抗dsDNA抗体価ほか、血清クレアチニン値、推算糸球体濾過量、1日蛋白尿との関連性は認められなかった。4)ION発生の有無に関してBMI、BSA、体重・BMI・BSAあたりのPSL初期投与量とに関連は認められなかった。一方、ION発生症例ではステロイド開始前とステロイド開始4週時の中性脂肪(TG)値は有意に上昇していた。以上より、ステロイド治療開始からTGを低下させることによりIONの発生が抑えられる可能性が示唆された。

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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DOI： 10.1186/1756-0500-7-641

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Language：Japanese   Publisher：中部リウマチ学会  

プレドニゾロン(PSL)0.5mg/kg/日以上の使用re用で開始された全身性エリテマトーデス(SLE)患者29例を対象に、スタチンを使用しなかったコントロール群(C群)5例(女性、平均29.6歳)、使用したスタチン群(S群)24例(男性2例、女性22例、平均42.4歳)に分け、スタチンの大腿骨頭壊死予防効果について検討した。PSL初期量は両群とも40〜60mg/日であった。その他、パルス療法、抗リン脂質抗体の有無について検討した。C群とS群において患者背景に差はなかった。比較的均一な治療を行い、スタチンを使用したが統計学的有意差は認められなかった。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Several studies have suggested an increased risk of malignant tumor in patients with rheumatoid arthritis. It has been also reported that rheumatoid arthritis patients have a high incidence of lymphoma compared with the general population, and that patients receiving methotrexate, which is the anchor drug for rheumatoid arthritis treatment, can develop lymphoproliferative disease. Nevertheless, management of rheumatoid arthritis after treatment for methotrexate-associated lymphoma has not been fully investigated. We here report a patient with rheumatoid arthritis who developed malignant lymphoma associated with methotrexate therapy. Moreover, we describe the use of a biologic agent for a rheumatoid arthritis patient after treatment for lymphoma associated with methotrexate. Case presentation. A 60-year-old Japanese man with a 20-year history of rheumatoid arthritis was admitted to our hospital with a left inguinal tumor. Open biopsy was performed and a biopsy specimen revealed diffuse large B-cell lymphoma. As our patient had received methotrexate for 4 years, we diagnosed the lymphoproliferative disease as being methotrexate-related. This lymphoma was not associated with Epstein- Barr virus by Epstein-Barr virus-encoded ribonucleic acid in-situ hybridization, but this patient was an Epstein-Barr virus carrier, regarding serological testing. The lymphoma went into complete remission after 6 courses of rituximab plus cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone/prednisolone therapy. Two years later, however, rheumatoid arthritis activity gradually increased and was not controlled with salazosulfapyridine. Etanercept was administered in view of its possible effect on B-cells, and this reduced the level of disease activity without recurrence of lymphoma. Conclusion: The management of rheumatoid arthritis after treatment for methotrexate-associated lymphoma has not been fully investigated yet. Etanercept appeared to be safe because of its B-cell effect, but further observation is necessary to make a firm conclusion. Further accumulation of cases is needed to clarify which biologics are safe and effective for treatment of methotrexate-associated B-cell lymphoma. © 2014 Kuroda et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1756-0500-7-229

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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A 77-year-old man developed severe renal insufficiency due to proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, and was started on hemodialysis (HD). Because his renal insufficiency appeared to be irreversible, he was maintained on oral prednisolone (PSL) at 5 mg/day. However, a disease flare-up with alveolar hemorrhage occurred. Serology revealed elevated levels of PR3-ANCA and C-reactive protein (CRP). The patient was given pulse therapy with a quarter dose of methylprednisolone (m-PSL) (250 mg, 3 days), followed by oral PSL at 15 mg/day. As a supplemental treatment, he was given 25 mg of mizoribine (MZR) immediately after each HD session. Subsequently, the levels of PR3-ANCA and CRP decreased, and the alveolar hemorrhage resolved. The dose of MZR to be given was determined by measuring the patient's serum concentrations of MZR at various time points after the HD session. The maintenance dose of MZR was finally set at 50 mg. At present, the oral PSL dosage has been tapered to 10 mg/day, and the patient has achieved a state of remission without any side effects.

DOI： 10.1007/s13730-012-0050-1

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Language：Japanese   Publisher：日本サルコイドーシス  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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A 36-year-old woman was diagnosed with systemic lupus erythematosus (SLE). Seven days after beginning glucocorticoid treatment, she developed reduced visual acuity, and atypical severe central serous chorioretinopathy (CSC) was confirmed. Since glucocorticoid use is an important risk factor for CSC, the PSL was reduced, tacrolimus was added, and the visual acuity improved rapidly. Reduction in glucocorticoid combined with the use of immunosuppressive agents is one option for preventing a deterioration in atypical severe CSC while still controlling SLE. © 2012 Japan College of Rheumatology.

DOI： 10.1007/s10165-012-0629-6

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We report a case of orbital tumor and hypertrophic cranial pachymeningitis in a 64-year-old woman, who was initially suspected to have IgG4-related disease because of an elevated level of serum IgG4 at onset. However, her condition was resistant to glucocorticoid therapy, and additional cyclophosphamide was necessary to control the disease activity. Additional features included elevated levels of serum myeloperoxidase (MPO) and proteinase-3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), and biopsy specimens from the orbital mass revealed very few infiltrating IgG4-positive cells. Instead, rupture of the elastic layer of the arterial walls with neovascularization and a small number of giant cells were observed. Considering these findings and the clinical course, the disease was considered more likely to be ANCA-associated pachymeningitis with elevation of the serum IgG4 level. © 2012 Japan College of Rheumatology.

DOI： 10.1007/s10165-012-0613-1

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

We report a case of orbital tumor and hypertrophic cranial pachymeningitis in a 64-year-old woman, who was initially suspected to have IgG4-related disease because of an elevated level of serum IgG4 at onset. However, her condition was resistant to glucocorticoid therapy, and additional cyclophosphamide was necessary to control the disease activity. Additional features included elevated levels of serum myeloperoxidase (MPO) and proteinase-3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), and biopsy specimens from the orbital mass revealed very few infiltrating IgG4-positive cells. Instead, rupture of the elastic layer of the arterial walls with neovascularization and a small number of giant cells were observed. Considering these findings and the clinical course, the disease was considered more likely to be ANCA-associated pachymeningitis with elevation of the serum IgG4 level.

DOI： 10.1007/s10165-012-0613-1

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Background: We previously reported that the amount of amyloid A (AA) amyloid deposited in renal biopsy specimens was highly correlated with parameters of renal function. However, the distribution of amyloid deposits throughout the kidneys of these patients, and the degree of renal abnormality, remained unclear. Therefore, we describe the features of reactive amyloidosis associated with rheumatoid arthritis (RA) in an autopsied patient. Case presentation. The present report case is a 50-year-old female with RA and reactive amyloidosis. She was diagnosed as RA in 1978. Diagnosis of AA amylodosis was made by renal biopsy in 1991 for the reason of proteinuria. Because of the pancreatitis, she was died in 2006 and autopsy was performed. Renal tissues from autopsy specimens were evaluated for their proportions of amyloid-positive areas. A total of 6 specimens (three tissue blocks from each kidney obtained at autopsy) were evaluated in this study. The size of each block was approximately 20 mm × 20 mm. One section of whole tissue was photographed in each case. The borders of the amyloid-positive areas in each specimen were traced in each photograph, excluding any tissue-free spaces. The total amyloid-positive area was measured, and the percentage area of amyloid per whole-tissue section (percent (%) area of amyloid deposition) was calculated. The distribution of amyloid deposits in the kidneys was examined. The significance of differences in the mean percent (%) area of amyloid deposition between the right and left sides and among three long-axis levels (upper, middle and lower) were analyzed by two-way analysis of variance (ANOVA) at a significance level of p &lt
0.05. Conclusion: The area of amyloid deposition in these samples was about 7-11%, and the degree of variability among them seemed to be small. It also shows a comparison of amyloid deposition between the right and left sides and between the long axis samples for quadruplicate determinations
no significant differences were evident, and thus the percent (%) area of amyloid deposition throughout the whole kidneys appeared to be uniform in this patient. © 2013 Kuroda et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1756-0500-6-231

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The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied by amyloid was &lt
10% in 54 of them. Mesangial proliferative glomerulonephritis and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, the percentage of the area occupied by amyloid was transformed to a common logarithmic value (Log10 % amyloid), as the histograms showed a log-normal distribution. Log10 % amyloid was found to be correlated with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear regression analyses were then performed to examine the sex- and age-adjusted association between Log10 % amyloid and each of the clinical variables. Cr, Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log10 % amyloid, but urinary protein was not. There was a significant correlation between the area of amyloid deposition in renal tissue and parameters of renal function, especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or prevented, then it may be possible to maintain renal function at an acceptable level. © 2011 Springer-Verlag.

DOI： 10.1007/s00296-011-2148-8

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

The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied by amyloid was &lt; 10% in 54 of them. Mesangial proliferative glomerulonephritis and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, the percentage of the area occupied by amyloid was transformed to a common logarithmic value (Log(10) % amyloid), as the histograms showed a log-normal distribution. Log(10) % amyloid was found to be correlated with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear regression analyses were then performed to examine the sex- and age-adjusted association between Log(10) % amyloid and each of the clinical variables. Cr, Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log(10) % amyloid, but urinary protein was not. There was a significant correlation between the area of amyloid deposition in renal tissue and parameters of renal function, especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or prevented, then it may be possible to maintain renal function at an acceptable level.

DOI： 10.1007/s00296-011-2148-8

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Language：Japanese   Publisher：中部リウマチ学会  

75歳女。HCV抗体陽性であったが、PCR法でHCV-RNAは検出されず、HCV既感染パターンと考えられた。インフリキシマブを使用することにより約2ヵ月で臨床的寛解が得られ、この間の肝機能検査値に大きな変動は認めなかった。

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当院通院中のRA患者491例(男性113例、女性378例)を対象に、越智分類に基づく関節破壊進行度(関節破壊の広がり)の性差について検討した。同分類における少関節破壊型(LES)を"軽症"とし、多関節破壊型(MES)とムチランス型(MUD)を"重症"として、軽症・重症それぞれの頻度を男女別で比較した。結果、男性ではLESが88例(78%)、MESが25例(22%)で、MUDは1例もなかったのに対し、女性はLES 214例(57%)、MES 147例(39%)、MUD 17例(4%)であり、男性に比べて重症の頻度が有意に高かった。

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Language：Japanese   Publisher：中部リウマチ学会  

RAにおいて抗CCP抗体は、診断だけでなく関節破壊の予後予測因子としても有用といわれている。Van Dongenらは、診断未確定の関節炎患者を対象とした2.5年間の経過観察で、抗CCP抗体陰性例ではMTX使用の有無で関節破壊の進行に違いがなかったと報告している。そこで今回、抗CCP抗体陰性RA例では長期的にも関節破壊が進行しにくいのかについて検討した。方法は、当院通院中のRA患者のうち罹病期間が5年以上の389例を対象とし、抗CCP抗体陰性群(53例)と陽性群に分け、越智の分類に基づく関節破壊進行度(関節破壊の広がり)を群間比較した。結果、抗CCP抗体陰性群は陽性群に比べて関節進行度の低い「少関節破壊型」例の割合が有意に高かった。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: The kidney is a major target organ for systemic amyloidosis that often affects the kidney including proteinura, and elevated serum creatinine (Cr). The correlation between amount of amyloid deposits and clinical parameters is not known. The aim of this study was to clarify correlation the amyloid area in all renal biopsy specimen and clinical parameters.
Methods: Fifty-eight patients with an established diagnosis of AL amyloidosis participated in the study. All patients showed amyloid deposits in renal biopsies. We retrospectively investigated the correlation between clinical data and amyloid occupied area in whole renal biopsy specimens.
Results: The area occupied by amyloid was less than 10% in 57 of the 58 patients, and was under 2% in 40. For statistical analyses, %amyloid-positive areas were transformed to common logarithmic values (Log(10)%amyloid). Cr showed significant correlation with Log(10)%amyloid and estimated glomerular filtration rate (eGFR) showed the significant negative correlation. Patient age, cleatinine clearance (Ccr), blood urea nitorogen, and urinary protein was not significantly correlated with Log(10)%amyloid. The correlation with other clinical factors such as sex, and serum concentrations of total protein, albumin, immunoglobulins, compliments was evaluated. None of these factors significantly correlated with Log(10)%amyloid. According to sex- and age- adjusted multiple linear regression analysis, Log(10)%amyloid had significant positive association with Cr and significant negative association with eGFR.
Conclusion: There is significant association between amyloid-positive area in renal tissue and renal function, especially Cr and eGFR. The level of Cr and eGFR may be a marker of amount of amyloid in renal tissue.

DOI： 10.1186/1471-2369-13-118

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：J RHEUMATOL PUBL CO  

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by many complications, and serious infections are associated with many of the advanced therapeutics used to treat it. We assessed serum procalcitonin (PCT) levels to distinguish bacterial infection from other complications in patients with RA.
Methods. One hundred eighteen patients experiencing an RA flare, noninfectious complication of RA or its treatment, nonbacterial infection, or bacterial infection were studied. Serum PCT concentrations were determined with a chemiluminescent enzyme immunoassay.
Results. All patients experiencing an RA flare showed negative PCT levels (&lt;= 0.1 ng/ml; n = 18). The PCT level was higher in the bacterial infection group (25.8% had levels &gt;= 0.5 ng/ml) than in the other 3 groups (0.0-4.3% had levels &gt;= 0.5 ng/ml) and the difference was significant among groups (p = 0.003). Conversely, no statistically significant difference was observed among the groups with C-reactive protein (CRP) concentration &gt;= 0.3 mg/dl (p = 0.513), white blood cell (WBC) count &gt; 8500/mm(3) (p = 0.053), or erythrocyte sedimentation rate (ESR) &gt; 15 mm/h (p = 0.328). The OR of high PCT level 0.5 ng/ml) for detection of bacterial infection was 19.13 (95% CI 2.44-149.78, p = 0.005). Specificity and positive likelihood ratio of PCT &gt;= 0.5 ng/ml were highest (98.2% and 14.33, respectively) for detection of bacterial infection, although the sensitivity was low (25.8%).
Conclusion. Serum PCT level is a more specific marker for detection of bacterial infection than either CRP, ESR, or WBC count in patients with RA. High PCT levels 0.5 ng/ml) strongly suggest bacterial infection. However, PCT &lt; 0.5 ng/ml, even if &lt; 0.2 ng/ml, does not rule out bacterial infection and physicians should treat appropriately. (First Release July 1 2012; J Rheumatol 2012;39:1517-23; doi:10.3899/jrheum.111601)

DOI： 10.3899/jrheum.111601

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：J RHEUMATOL PUBL CO  

Objective. Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy.
Methods. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated.
Results. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance.
Conclusion. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate. (First Release May 15 2012; J Rheumatol 2012;39:1348-54; doi:10.3899/jrheum.111453)

DOI： 10.3899/jrheum.111453

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In this report, we describe a case of a 48-yearold Japanese woman who is a hepatitis B (HB) carrier with rheumatoid arthritis (RA). She had the following antibody profile: HBs Ag(+), HBs Ab(-), HBe Ag(-), HBe Ab (+), HBc Ab(-) and undetectable HBV-DNA level. She was treated with auranofin, salazosulfapyridine, and bucillamine. Finally, she was treated with D-penicillamine, but her disease activity remained elevated. Prophylactic treatment of entecavir 0.5 mg daily was started in March 2008 and all disease-modifying anti-rheumatic drugs were stopped. After 2 weeks, etanercept monotherapy was started at 25 mg subcutaneously once a week. Significant improvement in clinical parameters of disease activity and well being was observed. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and HB virus viral load did not change significantly. Serum ALT, AST, and HB virus viral load were followed-up at every 3-month intervals, from initiation of therapy up to 24 months after the start of treatment with etanercept. We have also summarized the course of nine RA patients who received etanercept and were HB carriers or had chronic HB according to our literature search. Based on the results of our study, treatment of these patients with etanercept co-administered with lamivudine or entecavir appears to be safe. © Springer-Verlag 2010.

DOI： 10.1007/s00296-009-1344-2

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Our study was aimed to clarify an association between gastrointestinal (GI) amyloid-positive area and various kinds of factors including renal function in reactive amyloidosis associated with rheumatoid arthritis (RA). Twenty-five patients with an established diagnosis of reactive AA amyloidosis participated in the study between January 1989 and December 2009. Each patient satisfied the 1987 American Rheumatism Association criteria for RA. All patients showed amyloid deposits in both of GI and renal tissues. The average amyloid-deposited area was 2.2% in renal tissues and 3.7% in GI tissues although the difference was not statistically significant. Twenty-two patients out of 25 patients showed less than 5% of amyloidosis in renal tissues and nineteen patients showed 5% of amyloidosis in GI tissues. In 5 out of a total of 25 cases, the amyloid-deposited area in GI tissues was lesser than that in renal tissues. Mesangial proliferative glomerulonephritis, thin basement membrane disease (TBMD) and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, renal and GI tissues of % amyloid-positive areas were transformed to common logarithmic values (Log10%amyloid), since the histograms showed log-normal distribution. Clinical data were assessed by patient record at the time of GI biopsy. The correlation between Log10%GI-amyloid and age, creatinine (Cr), creatinine clearance (Ccr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR) were not significantly associated with Log10%GI-amyloid in crude correlation analyses and also in sex- and ageadjusted linear regression analyses. Although GI biopsy was not correlated with clinical factors, GI amyloid-positive areas were larger than renal amyloid-positive areas. Endoscopic screening of the upper GI tract is common in Japan, and amyloid-deposited area in GI tissues was sufficient to use for the diagnosis of amyloidosis compared with renal tissues in terms of convenience and sensitivity. © Springer-Verlag 2011.

DOI： 10.1007/s00296-010-1719-4

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Our study was aimed to clarify an association between gastrointestinal (GI) amyloid-positive area and various kinds of factors including renal function in reactive amyloidosis associated with rheumatoid arthritis (RA). Twenty-five patients with an established diagnosis of reactive AA amyloidosis participated in the study between January 1989 and December 2009. Each patient satisfied the 1987 American Rheumatism Association criteria for RA. All patients showed amyloid deposits in both of GI and renal tissues. The average amyloid-deposited area was 2.2% in renal tissues and 3.7% in GI tissues although the difference was not statistically significant. Twenty-two patients out of 25 patients showed less than 5% of amyloidosis in renal tissues and nineteen patients showed 5% of amyloidosis in GI tissues. In 5 out of a total of 25 cases, the amyloid-deposited area in GI tissues was lesser than that in renal tissues. Mesangial proliferative glomerulonephritis, thin basement membrane disease (TBMD) and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, renal and GI tissues of % amyloid-positive areas were transformed to common logarithmic values (Log(10)%amyloid), since the histograms showed log-normal distribution. Clinical data were assessed by patient record at the time of GI biopsy. The correlation between Log(10)%GI-amyloid and age, creatinine (Cr), creatinine clearance (Ccr), blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR) were not significantly associated with Log(10)%GI-amyloid in crude correlation analyses and also in sex- and age-adjusted linear regression analyses. Although GI biopsy was not correlated with clinical factors, GI amyloid-positive areas were larger than renal amyloid-positive areas. Endoscopic screening of the upper GI tract is common in Japan, and amyloid-deposited area in GI tissues was sufficient to use for the diagnosis of amyloidosis compared with renal tissues in terms of convenience and sensitivity.

DOI： 10.1007/s00296-010-1719-4

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In this report, we describe a case of a 48-year-old Japanese woman who is a hepatitis B (HB) carrier with rheumatoid arthritis (RA). She had the following antibody profile: HBs Ag(+), HBs Ab(-), HBe Ag(-), HBe Ab (+), HBc Ab(-) and undetectable HBV-DNA level. She was treated with auranofin, salazosulfapyridine, and bucillamine. Finally, she was treated with d-penicillamine, but her disease activity remained elevated. Prophylactic treatment of entecavir 0.5 mg daily was started in March 2008 and all disease-modifying anti-rheumatic drugs were stopped. After 2 weeks, etanercept monotherapy was started at 25 mg subcutaneously once a week. Significant improvement in clinical parameters of disease activity and well being was observed. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and HB virus viral load did not change significantly. Serum ALT, AST, and HB virus viral load were followed-up at every 3-month intervals, from initiation of therapy up to 24 months after the start of treatment with etanercept. We have also summarized the course of nine RA patients who received etanercept and were HB carriers or had chronic HB according to our literature search. Based on the results of our study, treatment of these patients with etanercept co-administered with lamivudine or entecavir appears to be safe.

DOI： 10.1007/s00296-009-1344-2

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Hypogammaglobulinemia is a reduction or absence of immunoglobulin, which may be congenital or associated with immunosuppressive therapy. In addition to infectious diseases, autoimmune diseases have also been reported in patients with hypogammaglobulinemia. A 26-year-old man with hypogammaglobulinemia had multiple joint pain and swelling with erosive changes in the proximal interphalangeal joint of the right middle finger on X-ray film, mimicking rheumatoid arthritis (RA). As polyarthritis remained after immunoglobulin replacement therapy and there was no finding indicating any infection at that time, a diagnosis of RA was made. Prednisolone and etanercept were started. However, his polyarthritis did not improve and he developed meningitis and massive brain ischemia. Finally, a diagnosis of disseminated Mycoplasma hominis infection was made. The differential diagnosis of polyarthritis in patients with hypogammaglobulinemia should strictly exclude Mycoplasma infection by culture with special media or longer anaerobic culture, and molecular methods for mycoplasma. © 2012 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.51.6058

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DOI： 10.2169/internalmedicine.51.6058

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Reactive amyloidosis is a serious systemic disease in rheumatoid arthritis (RA). Amyloid protein can be deposited in kidneys, heart or gastrointestinal tract leading to organ failure. Renal involvement is a wellknown complication in amyloidosis as this may culminate in end-stage renal disease (ESRD). Hemodialysis (HD) is always considered the treatment of choice for such patients
however, the prognosis is usually poor due to a large number of sudden deaths immediately following HD therapy. To circumvent the problem of HD initiation while instituting HD safety, we devised a plan to start HD and compare patient's survival with our previous data. Sixtythree patients were treated with HD. They were categorized according to the initiation of first dialysis. All patients were divided into planned, unplanned and programmed initiation groups. First dialysis that had been initiated as not urgent was considered 'planned' (20 patients). First dialysis that had been performed urgently for life-threatening renal insufficiency was considered 'unplanned' (31 patients). First dialysis that had been initiated as not urgent and according to our dialysis program was considered 'programmed' (12 patients). Survival of these 63 patients from the initiation of HD at 38 days was 75%, at 321 days was 50% and at 1,784 days was 25%. Patients with unplanned initiation of HD showed a significant poor survival compared with those of both planned and programmed initiation. Additionally, patients with planned and programmed initiation of HD showed no significant difference for the patients' survival. Our study demonstrates that patients with amyloidosis have a higher mortality rate. Nevertheless, programmed initiation of HD will improve the prognosis of patients with ESRD. Such possibility needs to be considered in more detail in the future. © 2010 Springer-Verlag.

DOI： 10.1007/s00296-010-1448-8

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

Reactive amyloidosis is a serious systemic disease in rheumatoid arthritis (RA). Amyloid protein can be deposited in kidneys, heart or gastrointestinal tract leading to organ failure. Renal involvement is a well-known complication in amyloidosis as this may culminate in end-stage renal disease (ESRD). Hemodialysis (HD) is always considered the treatment of choice for such patients; however, the prognosis is usually poor due to a large number of sudden deaths immediately following HD therapy. To circumvent the problem of HD initiation while instituting HD safety, we devised a plan to start HD and compare patient's survival with our previous data. Sixty-three patients were treated with HD. They were categorized according to the initiation of first dialysis. All patients were divided into planned, unplanned and programmed initiation groups. First dialysis that had been initiated as not urgent was considered 'planned' (20 patients). First dialysis that had been performed urgently for life-threatening renal insufficiency was considered 'unplanned' (31 patients). First dialysis that had been initiated as not urgent and according to our dialysis program was considered 'programmed' (12 patients). Survival of these 63 patients from the initiation of HD at 38 days was 75%, at 321 days was 50% and at 1,784 days was 25%. Patients with unplanned initiation of HD showed a significant poor survival compared with those of both planned and programmed initiation. Additionally, patients with planned and programmed initiation of HD showed no significant difference for the patients' survival. Our study demonstrates that patients with amyloidosis have a higher mortality rate. Nevertheless, programmed initiation of HD will improve the prognosis of patients with ESRD. Such possibility needs to be considered in more detail in the future.

DOI： 10.1007/s00296-010-1448-8

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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We report a case of Churg-Strauss syndrome (CSS) complicated by severe cardiac failure and peripheral neuropathy. Two courses of methylprednisolone pulse therapy were unable to control the disease activity. Repeated intravenous administration of high-dose human immunoglobulin (IVIg) was added together with intravenous cyclophosphamide pulse therapy (IVCY), and the patient's cardiac function and neurological symptoms were gradually ameliorated without any adverse event. Although glucocorticoid and cyclophosphamide comprise the standard therapy for patients with CSS, a number of patients with severe complications appear to be resistant to such conventional treatment. IVIg is thought to be an effective therapeutic option for such patients. © 2011 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.50.4648

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We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid. © 2011 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.50.4876

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

We report a case of Churg-Strauss syndrome (CSS) complicated by severe cardiac failure and peripheral neuropathy. Two courses of methylprednisolone pulse therapy were unable to control the disease activity. Repeated intravenous administration of high-dose human immunoglobulin (IVIg) was added together with intravenous cyclophosphamide pulse therapy (IVCY), and the patient&apos;s cardiac function and neurological symptoms were gradually ameliorated without any adverse event. Although glucocorticoid and cyclophosphamide comprise the standard therapy for patients with CSS, a number of patients with severe complications appear to be resistant to such conventional treatment. IVIg is thought to be an effective therapeutic option for such patients.

DOI： 10.2169/internalmedicine.50.4648

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

We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid.

DOI： 10.2169/internalmedicine.50.4876

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Anti-neutrophil cytoplasmic autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) are known to be present in patients with cystic fibrosis, diffuse panbronchiolitis, and inflammatory bowel disease, especially in relation to chronic Gram-negative bacterial infection. To investigate the possible role of BPI-ANCA in rheumatoid arthritis (RA), we measured the serum titer of BPI-ANCA and examined clinical manifestations, including pulmonary complications, in patients with RA. Seventy-four RA patients were recruited to our study. The titer of BPI-ANCA was measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary complications were evaluated using high-resolution computed tomography (HRCT), which revealed 26 patients with bronchial diseases (BD group), 25 with interstitial pneumonia (IP group), and 23 without any particular lung lesion (normal group). The correlations between the titer of BPI-ANCA and patients' clinical and laboratory findings were then analyzed. The numbers of tender joints, swollen joints, and the Disease Activity Score including 28 joint count were significantly higher in the BD group. The titer of BPI-ANCA was positively correlated with age, erythrocyte sedimentation rate (ESR), and bronchial involvement in all subjects. Stepwise multiple regression analysis of factors affecting the titer of BPI-ANCA selected ESR and bronchial involvement as independent variables. Our results show that BPI-ANCA was positively correlated with chronic inflammatory status in RA patients, and we is believe it is positively linked with bronchial diseases.

DOI： 10.1007/s10165-009-0270-1

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We describe a 20-year-old female with systemic lupus erythematosus (SLE) who developed renal failure during continuous ambulatory peritoneal dialysis (CAPD). The patient was treated with mizoribine (MZR). MZR peak concentration was 1.8 mu g/ml and was sufficient for clinical efficacy as measured by serological data. Treatment with MZR was safe and useful even while undergoing CAPD. Achieving optimal MZR blood concentration was important for treatment of SLE, even though the patient was in end-stage renal failure.

DOI： 10.1007/s10165-009-0267-9

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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A 53-year-old Japanese woman, without any specific medical or family history, was admitted to our hospital for acute renal failure with macrohematuria. Routine blood analysis, including blood coagulation test, revealed azotemia accompanied by prolonged activated partial thromboplastin time (aPTT). Computed tomography revealed bilateral kidney swelling with dilatation of the renal pelvis. An extensive coagulation analysis revealed that the concentration of factor VIII had decreased to 1.8% and the level of factor VIII inhibitor was markedly elevated to 19 BU/ml. The final diagnosis was acquired hemophilia induced by autoantibodies against factor VIII, which was complicated by postrenal acute renal failure due to the obstruction of urinary tracts by renal bleeding and clots. The patient was treated with a combination of prednisolone at a dose of 50 mg/day (1 mg/kg body weight) and cyclophosphamide. The levels of factor VIII inhibitor decreased gradually, and the activity of factor VIII was improved after treatment. The levels of aPTT and concentrations of factor VIII and factor VIII inhibitor were monitored during the subsequent follow-ups. © 2009 Japanese Society of Nephrology.

DOI： 10.1007/s10157-009-0226-y

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A 53-year-old Japanese woman, without any specific medical or family history, was admitted to our hospital for acute renal failure with macrohematuria. Routine blood analysis, including blood coagulation test, revealed azotemia accompanied by prolonged activated partial thromboplastin time (aPTT). Computed tomography revealed bilateral kidney swelling with dilatation of the renal pelvis. An extensive coagulation analysis revealed that the concentration of factor VIII had decreased to 1.8% and the level of factor VIII inhibitor was markedly elevated to 19 BU/ml. The final diagnosis was acquired hemophilia induced by autoantibodies against factor VIII, which was complicated by postrenal acute renal failure due to the obstruction of urinary tracts by renal bleeding and clots. The patient was treated with a combination of prednisolone at a dose of 50 mg/day (1 mg/kg body weight) and cyclophosphamide. The levels of factor VIII inhibitor decreased gradually, and the activity of factor VIII was improved after treatment. The levels of aPTT and concentrations of factor VIII and factor VIII inhibitor were monitored during the subsequent follow-ups.

DOI： 10.1007/s10157-009-0226-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer-Verlag Tokyo  

We describe a 20-year-old female with systemic lupus erythematosus (SLE) who developed renal failure during continuous ambulatory peritoneal dialysis (CAPD). The patient was treated with mizoribine (MZR). MZR peak concentration was 1.8 μg/ml and was sufficient for clinical efficacy as measured by serological data. Treatment with MZR was safe and useful even while undergoing CAPD. Achieving optimal MZR blood concentration was important for treatment of SLE, even though the patient was in end-stage renal failure. © Japan College of Rheumatology 2010.

DOI： 10.1007/s10165-009-0267-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer-Verlag Tokyo  

Anti-neutrophil cytoplasmic autoantibodies against bactericidal/ permeability-increasing protein (BPIANCA) are known to be present in patients with cystic fibrosis, diffuse panbronchiolitis, and inflammatory bowel disease, especially in relation to chronic Gram-negative bacterial infection. To investigate the possible role of BPIANCA in rheumatoid arthritis (RA), we measured the serum titer of BPI-ANCA and examined clinical manifestations, including pulmonary complications, in patients with RA. Seventy-four RA patients were recruited to our study. The titer of BPI-ANCA was measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary complications were evaluated using high-resolution computed tomography (HRCT), which revealed 26 patients with bronchial diseases (BD group), 25 with interstitial pneumonia (IP group), and 23 without any particular lung lesion (normal group). The correlations between the titer of BPIANCA and patients' clinical and laboratory findings were then analyzed. The numbers of tender joints, swollen joints, and the Disease Activity Score including 28 joint count were significantly higher in the BD group. The titer of BPIANCA was positively correlated with age, erythrocyte sedimentation rate (ESR), and bronchial involvement in all subjects. Stepwise multiple regression analysis of factors affecting the titer of BPI-ANCA selected ESR and bronchial involvement as independent variables. Our results show that BPI-ANCA was positively correlated with chronic inflammatory status in RA patients, and we is believe it is positively linked with bronchial diseases. © Japan College of Rheumatology 2010.

DOI： 10.1007/s10165-009-0270-1

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DOI： 10.3109/03009740903042402

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：J RHEUMATOL PUBL CO  

Objective. To examine the effect of anti-tumor necrosis factor-alpha (anti-TNF) therapy in patients with reactive AA amyloidosis associated with rheumatoid arthritis (RA).
Methods. Fourteen patients with reactive AA amyloidosis associated with RA were prospectively evaluated. Four patients were treated with infliximab and 10 with etanercept. The mean period of anti-TNF therapy was 20.1 +/- 13.8 months. Laboratory findings and renal function were examined before and after initiation of anti-TNF therapy. In 9 patients the area of amyloid deposits in serial gastroduodenal mucosal biopsy specimens was examined and image analysis was performed.
Results. C-reactive protein and serum amyloid A protein levels were significantly reduced after initiation of anti-TNF therapy. Twenty-four hour creatinine clearance improved in 4 patients, did not change in 5, and deteriorated in 3. Twenty-four hour urinary protein excretion was significantly decreased in 3 patients, not exacerbated in 6, and increased in 3 after initiation of anti-TNF therapy. The biopsy specimens from the 9 patients Who underwent serial gastroduodenal biopsies showed significant decreases in the area of amyloid deposits, from 8.8% +/- 6.4% to 1.6% +/- 0.6% (p = 0.003) after initiation of anti-TNF therapy. Four patients showed a Sustained decrease in the areas of amyloid deposits in their third biopsy specimens, and amyloid deposits were not detectable in 2.
Conclusion. Our results indicate a striking effect of anti-TNF therapy for rapid removal and sustained disappearance of amyloid deposits in gastric mucosal tissue with amelioration of renal functions in patients with reactive amyloidosis due to RA. (First Release Oct 1 2009; J Rheumatol 2009; 36:2409-15; doi: 10.3899/jrheum.090101)

DOI： 10.3899/jrheum.090101

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Language：Japanese   Publisher：日本臨床免疫学会  

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55歳女。関節リウマチ(RA)であり、左人工膝関節置換術、左肘滑膜切除術が施行され、MTXを投与されていたが、尿蛋白が出現し、腎生検でアミロイドーシスと診断された。入院時、下腿に浮腫があり、両手指MP、DIP関節および左膝関節に疼痛腫脹と、両側肘関節にリウマトイド結節を認めた。検査成績では血沈の著明亢進、凝固能検査で凝固能の亢進を認め、また、軽度の低蛋白血症とガンマグロブリン分画の増加を認め、CRP、SAA、BNPは上昇していた。尿蛋白は定性で3+であり、沈渣には顆粒円柱も認められた。尿蛋白は1日4.4gと増加しており、クレアチニンクリアランス(Ccr)は54.0ml/分、腎クリアランステストでも糸球体濾過率(GFR)は46.0ml/分と低下していた。インフリキシマブを開始し、CRPは速やかに改善し、SAAも著明に低下した。蛋白尿は徐々に低下し、減少傾向にあったCcrはインフリキシマブ開始後上昇傾向となった。腎生検所見では糸球体が21個観察され、7個がglobal sclerosisで、残り半分以上の糸球体にamyloidの沈着を認めた。また、間質の一部にもamyloidの沈着を認め、電顕でもamyloid線維が確認された。インフリキシマブ使用前後の胃・十二指腸粘膜生検の組織については、開始前は血管を中心に全標本でCongo-red陽性のアミロイドの沈着をかなり認めたが、1年後は殆ど認めなかった。

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DOI： 10.1152/ajprenal.00075.2008

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Background A sol particle homogeneous immunoassay (SPIA) is a method to measure the serum cystatin C (cysC) level as a marker of the glomerular filtration rate (GFR). Recently, formulas to convert measured cysC to GFR have been developed.
Methods A total of 154 patients (46 +/- 18 years old) who had undergone renal biopsy, sodium thiosulfate clearance (C(thio)) and 24-h creatinine clearance (24-hCcr) tests were subjects for the study. Their serum cysC levels were determined by SPIA.
Results Multiple regression analysis revealed Cthio and age as independent variables for serum creatinine concentration (Cr), while only C(thio) affected cysC. The equations using Cr or cysC showed significant correlation with C(thio). Receiver-operating curve ROC analysis revealed that cysC and 24-hCcr shared comparable power to detect patients with GFR &lt; 90 or 60 ml/min/1.73 m(2) (AUC = 0.862 and 0.943 vs. AUC = 0.842 and 0.943, respectively), while Cr (AUC = 0.881) and MDRD2 (AUC = 0.888) showed slightly inferior ability to detect 60 ml/min/1.73 m(2) than other parameters in the female population. The cut-off point of cysC and Cr obtained from the ROC analysis demonstrated strong power to detect patients with C(thio) &lt; 90ml/min/1.73 m(2) or C(thio) &lt; 60 ml/min/1.73 m(2). According to CKD stages, the mean values of each equation were significantly different, like that demonstrated by 24-hCcr.
Conclusion SPIA could determine cysC levels that detected early renal impairment. The accuracy of cysC to detect early renal impairment may be superior to that of Cr in females, while it would be comparable to that of CG or MDRD when they are corrected by sex and age. Both cysC itself and cysC equations are effective to monitor the progress of renal impairment. The future standardization of cysC measurements and development of novel equation of cysC would contribute to the further improvement of GFR estimation in clinical practice.

DOI： 10.1007/s10157-008-0047-4

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27歳男。潰瘍を伴う軟口蓋腫瘤が出現し、徐々に拡大して疼痛が増強した。PR3-ANCAが10.5U/mlと高値で、Wegener肉芽腫症(WG)の疑いで当科紹介入院となった。口腔内所見で歯肉のびらん潰瘍形成、軟口蓋の穿孔がみられ、入院後の検査所見では好中球分画の上昇を伴う白血球増多、CRP上昇、PR3-ANCA上昇を認めた。潰瘍部位からの生検では特異な血管炎の所見は得られず、歯肉のびらん潰瘍部からの生検では血管周囲にgranulomatousな炎症細胞浸潤とfibrinoid壊死を認め、WGと診断した。Prednisolone(PSL) 1mg/kgとcyclophosphamide(CPA) 50mgの内服を開始したが効果なく、methylprednisoloneのパルス療法を計5回施行し、CPAを125mgに増量してCRPは陰性化した。以後PSL漸減、CPAからMTX 10mg/週への変更を行い、疼痛はフェンタニルパッチ5mgで対処した。軟口蓋の潰瘍部は脱落し欠損したままであったため、口腔外科でprosthesisを作成し、経口摂取および会話が可能となり退院した。

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原発性シェーグレン症候群(SJ)54例(男1例・女53例・平均49歳:A群)、続発性SJ 48例(女・平均53歳:B群)、SJ非合併膠原病53例(男2例・女51例・平均48歳:C群)を対象に、抗Fodrin-α抗体(AF)を測定し、その測定意義を検討した。IgGクラスAFの陽性率はA群37%、B群23%、C群6%、IgAクラスAFは順に37%、27%、9%で、A群およびB群はC群に比較して有意に高値であった。なお、抗SS-A抗体および抗SS-B抗体の陽性率も同様の傾向であった。これらのSJにおける感度を比較したところ、抗SS-A抗体が81%で他の抗体(42〜30%)よりも有意に高値であったが、特異度は76%と他の抗体(91〜98%)より低値であった。抗体間の関係をみると、抗SS-A抗体とAFとはIgG、IgAクラスとも強い関連を認めたが、抗SS-B抗体とIgGクラスAFとは軽度関連、IgAクラスAFとは関連を認めなかった。AFはSJにおいて、抗SS-A、B抗体とは異なる測定意義を有すると考えられた。

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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DOI： 10.1007/s00296-008-0590-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ACAD PERIODONTOLOGY  

Background: The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines and immunoglobulin G Fc receptor (Fc gamma R) play an important role. Functional polymorphisms of interleukin (IL)-1 and Fc gamma R were shown to be associated with susceptibility to both diseases. Therefore, we evaluated whether the IL-1 and Fc gamma R gene polymorphisms represent a common risk factor for RA and periodontitis.
Methods: The study population consisted of Japanese adults with RA (RA group; N = 100), periodontitis only (P group; N = 100), and healthy individuals with no systemic or oral disease (H group; N = 100). Clinical periodontal condition was defined by measurements of probing depth, clinical attachment level, and bleeding on probing. Genomic DNA was isolated from peripheral blood and analyzed for determination of IL-1 genotypes (IL-1A+4845, IL-1B+3954, and IL-1RN+2028) and Fc gamma R genotypes (Fc gamma RIIA, Fc gamma RIIIA, and Fc gamma RIIIB) by allele-specific polymerase chain reactions.
Results: Among 100 patients with RA, 86% showed periodontal tissue destruction. However, the RA group exhibited milder levels of periodontal tissue destruction than the P group (P &lt; 0.01). There was a significant difference in the distribution of IL-1B+3954 C/T genotypes between the RA and P groups and between the RA and H groups (P= 0.03 for both comparisons), with enrichment of the T allele in the RA group (P= 0.04; odds ratio, 2.9 for both comparisons). The combination of IL-1A+4845 T and IL-1+3954 T alleles yielded a strong association with RA and periodontitis (RA versus P group: P= 0.00001; RA versus H group: P= 0.00001).
Conclusions: These results failed to show that IL-1 and Fc gamma R gene polymorphisms constitute a common risk factor for RA and periodontitis. However, it was suggested that the distributions of IL-1B+3954 genotypes and IL-1A+4845 and IL-1B+3954 haplotypes were unique to the patients with RA and periodontitis.

DOI： 10.1902/jop.2007.070136

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DOI： 10.1016/j.cca.2007.04.023

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Other Link： http://orcid.org/0000-0002-4294-8030

Language：Japanese   Publisher：中部リウマチ学会  

32歳女性。全身性エリテマトーデスの維持治療中に発熱、四肢の腫脹、四肢筋力の低下があり、筋原性酵素の上昇を認めた。入院時現症としてヘリオトロープ疹、ゴットロン徴候、近位筋の筋力低下がみられ、検査では白血球増多症、GOT、GPT、LDH、CKの著明増加、CRP陽性、抗Jo-1抗体陽性を認めた。また抗DNA抗体陽性、抗RNP抗体陰性であった。また左上腕二頭筋の筋生検で筋炎の所見を得、皮膚筋炎と診断した。入院後はプレドニゾロン(PSL)30mgを継続し、筋炎の所見を得た後にメチルプレドニゾロン1000mgのパルス療法を3日間施行、その後PSL 60mgの後療法を行った。結果としてCKは緩徐に減少し、それにつれてLDH等の逸脱酵素も減少傾向を示した。パルス療法後に発熱し、サイトメガロウイルス抗原陽性を認めたためガンシクロビルを使用した。2週間後に抗原の陰性化を認めて以後再燃なく、PSL漸減を開始し35mgにて退院となった。本症例は、異なる時相でSLEと筋炎が発症し、SLEに特徴的な抗DNA抗体、筋炎に特徴的な抗Jo-1抗体の双方が陽性である点から重複症候群と診断された。

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The clinical efficacy of mizoribine (MZR
4-carbamoyl-1-b-D- ribofuranosylimidazolium) in patients with lupus nephritis was investigated. Thirteen Japanese patients with biopsy-proved lupus nephritis were enrolled in this study. A change in global assessments score, total protein (TP) of serum, serum creatinine, creatinine clearance (Ccr), proteinuria, titers of serum anti-ds DNA antibody, C3, C4, and hemolytic complement activity (CH50) were examined. Following MZR treatment, the level of urinary protein decreased (P &lt
0.05), whereas the level of Ccr increased (P &lt
0.05). Moreover, the level of TP significantly increased from 5.5 g/dl to 6.3 g/dl (P &lt
0.01) and the level of C3 increased significantly (P &lt
0.01). However, there was no change in the levels of both C4 and CH50. The titer of anti-ds DNA antibody significantly decreased (P &lt
0.05). The dosage of prednisolone could be tapered from 24.8 mg to 14.9 mg daily during the period. The clinical effects associated with MZR concentration in the blood revealed that there was a significant correlation between the peak MZR blood concentration of more than 0.66 μg/ml and clinical improvement (P = 0.021). Our results suggest that an optimal MZR blood concentration was important for the treatment of lupus nephritis. © Japan College of Rheumatology 2007.

DOI： 10.1007/s10165-007-0567-x

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ACAD PERIODONTOLOGY  

Background: The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (Fc gamma R) and proinflammatory cytokines play an important role. Genetic variations of Fc gamma R and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of Fc gamma R or IL-1 polymorphic genes represents a common risk factor for SLE and periodontitis.
Methods: The study population consisted of Japanese adults with SLE and periodontitis (SLE+P group; n = 46), SLE only (SLE group; n = 25), periodontitis only (P group; n = 58), and healthy individuals with no systemic or oral disease (H group; n = 44). Clinical periodontal condition was evaluated by measurement of probing depth, clinical attachment level, and alveolar bone loss. Genomic DNA was isolated from peripheral blood and analyzed for determination of Fc gamma R genotypes (Fc gamma RIIA, Fc gamma RlIB, Fc gamma RIIIA, and Fc gamma RIIIB) and IL-1 genotypes (IL-1A +4845 and IL-1B +3954) by allele-specific polymerase chain reactions or DNA sequencing.
Results: A significant overrepresentation of the R 131 allele of stimulatory Fc gamma RIIA and the 232T allele of inhibitory Fc gamma RIIB was found in the SLE+P group compared to the H group (P=0.01 and P=0.0009, respectively). The combination of Fc gamma RIIA-R131 and Fc gamma RIIB-232T alleles yielded a strong association with SLE and periodontitis (SLE+P group versus P group: P=0.01, odds ratio: 3.3; SLE+P group versus H group: P = 0.0009, odds ratio: 11.2). Furthermore, SLE patients with the combined Fc gamma R risk alleles exhibited more severe periodontal tissue destruction compared to other SLE patients. The frequencies of IL-1 polymorphic alleles were too low to assess the association with SLE or periodontitis.
Conclusion: The combination of stimulatory Fc gamma RIIA and inhibitory Fc gamma RIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population.

DOI： 10.1902/jop.2007.060194

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Thrombotic thrombocytopenic purpura (TTP) is a rare complication of mixed connective tissue disease (MCTD). In this report, we describe the case of a 73-year-old Japanese woman with MCTD who developed fever, thrombocytopenia, and microangiopathic hemolytic anemia and was diagnosed with MCTD together with TTP. The activity of von Willebrand factor (vWF) cleaving metalloprotease ADAMTS13 was low and considered to have contributed to the disease activity of TTP. The patient died despite intensive treatment of plasma exchange (PEX) and steroid pulse therapy. Autopsy results revealed that the kidneys had platelet and fibrin thrombi, which occluded capillaries and arterioles. These findings were compatible with TTP and the decreased activity of ADAMTS13 was considered to be associated with the disease activity of TTP.

DOI： 10.1007/s10067-005-0105-1

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

Background/Aims: Our previous comprehensive analysis of the genes expressed in kidneys with anti-glomerular basement membrane ( GBM) nephritis using DNA microarrays showed that SM22 alpha was one of the highly expressed genes. SM22 alpha is a 22-kDa cytoskeletal protein that is exclusively expressed in smooth muscle cells. We investigated the localization of SM22 alpha at mRNA and protein levels, and its pathological significance in anti-GBM nephritis kidneys. Methods: Northern blot analysis, in situ hybridization, immunohistochemistry and double immunofluorescence studies were performed. The specific antibody ( Ab) against SM22 alpha was obtained by immunization of rabbits with recombinant rat SM22 alpha protein. Results: SM22 alpha mRNA expression was up-regulated in kidneys and inducibly expressed in the parietal and visceral glomerular epithelial cells in anti-GBM nephritis kidneys. Immunohistochemistry with anti-SM22 alpha Ab showed that SM22 alpha protein was localized in the same series of cells. Double immunofluorescence with anti-SM22 alpha and anti- glomerular cell markers demonstrated that SM22 alpha might be expressed in epithelial cells of injured glomeruli. In visceral epithelial cells, SM22 alpha might be expressed in cells in which podocyte specific markers, podocalyxin and nephrin were lost. Conclusion: The injured glomerular epithelial cells in anti-GBM nephritis might undergo structural and functional alterations, including the expression of a smooth muscle marker, SM22 alpha. Copyright (C) 2007 S. Karger AG, Basel.

DOI： 10.1159/000103020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<b>Objective</b> Alpha2-Heremans Schmid glycoprotein/Fetuin-A (AHSG) is a circulating negative acute-phase protein, which inhibits bimineralization. It is often considered as a potential mediator between chronic inflammation and cardiovascular diseases. The metabolism of AHSG in patients with rheumatoid arthritis (RA) is unknown.<br> <b>Methods</b> Serum AHSG concentrations were measured in 102 patients with RA using a newly developed indirect enzyme-linked immunosorbent assay (ELISA).<br> <b>Results</b> The serum AHSG levels in the RA patients were significantly lower than that in healthy volunteers (249.8 ± 84.1 vs 425.0 ± 93.0 μg/ml, P<0.0001). Serum C-reactive protein concentration and erythrocyte sedimentation rate were inversely correlated, while albumin, hemoglobin and total cholesterol were positively correlated with AHSG. Current serum AHSG levels did not affect the presence of aortic calcification, whereas cumulative glucocorticoid dosage was significantly related to aortic calcification (P=0.005).<br> <b>Conclusion</b> Serum AHSG levels were significantly decreased in patients with RA. The levels reflected inflammatory and malnutritional conditions. Its role in the development of cardiovascular diseases or inflammatory bone resorption remain uncertain in RA patients.<br>

DOI： 10.2169/internalmedicine.46.6269

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Other Link： http://search.jamas.or.jp/link/ui/2008171447

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DOI： 10.1038/sj.ki.5001941

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In this report, we describe the case of a 50-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria and renal dysfunction. Abdominal computed tomography did not show narrowing of both renal arteries. Although her levels of C-reactive protein were negative, plasma vascular endothelial growth factor (VEGF) and serum interleukin (IL)-6 levels were elevated. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis (MPGN) with glomerular capillary wall thickening (double contour). This was accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. These findings are quite different from MPGN as electron microscopy did not show subendothelial deposit and circumferential mesangial interposition. Here, we present the case of Takayasu arteritis associated with MPGN-like renal manifestation and elevated VEGF and IL-6. The presence of elevated VEGF and IL-6 could be factors that might contribute to MPGN-like appearance.

DOI： 10.1007/s00296-006-0156-x

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To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n = 153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis. © Japan College of Rheumatology 2006.

DOI： 10.1007/s10165-006-0500-8

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The aim was to analyze the clinical outcome of a group of 51 patients diagnosed with systemic amyloidosis associated with rheumatoid arthritis who received hemodialysis (HD) as renal replacement therapy. We monitored the clinical course of the disease and factors that could influence survival. Determination of the onset of the underlying disorder was made retrospectively by reviewing the patient's chart when a diagnosis of amyloid was confirmed. During a 96.9 person-year follow-up, 42 patients died. Survival of these 51 patients from the initiation of HD at 251 days was 50%. Poor prognosis in amyloid patients was mainly due to a large number of sudden deaths immediately following HD therapy. Out of 51 patients 21 needed unplanned initiation of HD. The unplanned initiation was significantly associated with poor survival. Seventy-five percentile of creatinine clearance (Ccr) was 9.7 ml/min, and 75% of these patients who initiated HD had highly impaired renal functional states. These data indicated that amyloidotic patients with HD showed a high mortality rate; therefore, planned initiation of HD was highly recommended to improve the patient's survival. Particular attention was given to the Ccr levels, because the levels of serum creatinine may not be a useful marker for some patients with amyloidosis.

DOI： 10.1007/s00296-006-0204-6

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It is well established that amyloidosis is a serious clinical complication that can influence the prognosis of patients with rheumatoid arthritis (RA). The purpose of the study was to obtain information on the survival and the hemodialysis (HD) of patients with amyloidosis. Eighty patients (9 men and 71 women) who were diagnosed with amyloidosis by biopsy and definite or classical RA were studied retrospectively. The average duration of RA prior to the diagnosis of amyloidosis was 15.4 +/- 9.4 years. The average period from the diagnosis of amyloidosis to death was 67.4 months. Forty-nine patients died of the disease (32 cases with HD and 17 cases without HD). Thirty-one patients lived (7 cases with HD and 24 cases without HD). Regarding the survival of these patients, 49 (61.3%) of the 80 patients have died. Survival rate at 28 months was 75%; at 67 months, it was 50%; and at I I I months, it was down to 25%. Mortality rate was 11.9% per year. Survival rate in dialysis at 9.8 months was 75%; at 60.6 months, it dropped to 50%; and at 100.0 months, to 25%. As for patients' survival, high onset age of amyloidosis was the major determining factor for poor survival in these patients (p &lt; 0.001). Furthermore, male patients also had poor survival (p=0.07). The long-term results were very encouraging to initiate HD in patients with end-stage renal disease due to reactive amyloidosis associated with RA.

DOI： 10.1007/s10067-005-0079-z

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Objectives: To examine the relationship between autoantibodies against oxidized low-density lipoprotein (oxLDL-Abs) and the progression of carotid atherosclerosis in patients with rheumatoid arthritis (RA). Methods: Fifty RA patients without evidence of risk factors for atherosclerosis (RA group) and 30 healthy volunteers (normal group) were investigated. The mean intima-media thickness of the common carotid artery (mean CCA-IMT) was measured by high-resolution B-mode ultrasonography. The titer of IgG oxLDL-Abs was measured by enzyme-linked immunosorbent assay. The relationships among mean CCA-IMT IgG oxLDL-Ab titer and patient factors such as body mass index, systolic blood pressure, diastolic blood pressure, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum lipid levels were examined. Results: Mean CCA-IMT, CRP, ESR and titer of IgG oxLDL-Abs were significantly higher in the RA group than in the normal group. Although mean CCA-IMT showed a positive correlation only with age in multivariate analysis, IgG oxLDL-Ab titers in the RA group were positively associated with mean CCA-IMT and independently with age and sex by multiple regression analysis. Conclusions: IgG oxLDL-Abs appear to be associated with the degree of carotid atherosclerosis in patients with RA, and are independent of traditional risk factors for atherosclerotic diseases. These results suggest a possible link between autoimmune mechanisms and accelerated atherosclerosis in RA. © Copyright Clinical and Experimental Rheumatology 2005.

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In this report we describe the case of identical twin sisters that developed systemic lupus erythematosus (SLE). These patients have in common major histocompatibility complex class I and class II alleles and identical red blood cell antigens, which is a clear indication of monozygotic twins. Both twins showed high titers of anti-dsDNA antibody. However, only one of them manifested signs of lupus psychosis and was positive for the LE test, rheumatoid factor, anti-Scl 70, anti-SSA, and antiribosomal P antibodies. Both sisters lived together
therefore, the environmental factors were considered to be the same. Interestingly, these patients expressed different types of autoantibodies and the manifestation of disease was also quite different. When one of the twins was diagnosed with SLE, we began to closely follow up signs of the disease in the other twin periodically. This enabled us to promptly diagnose the second twin with SLE and she was successfully treated without progression of the disease. It is important to mention that following up the subsequent history of an identical twin diagnosed with SLE allowed early detection of the disease in the other twin. © Japan College of Rheumatology and Springer-Verlag Tokyo 2005.

DOI： 10.1007/s10165-004-0365-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Inc.  

Background. The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARα on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model. Methods. The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells. Results. Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats. Conclusion. BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis. © 2005 by the International Society of Nephrology.

DOI： 10.1111/j.1523-1755.2005.00280.x

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We report on a 65-year-old Japanese woman with Takayasu arteritis who developed severe proteinuria, hypertension, and renal dysfunction. Renal angiography demonstrated moderate irregular narrowing of both renal arteries. Renal biopsy showed glomerulonephropathy mimicking membranoproliferative glomerulonephritis ( MPGN) with glomerular capillary wall thickening ("double contour'') accompanied by mesangial cell proliferation and moderate increase of mesangial matrix without deposits of C3. Electron microscopy showed no subendothelial deposit and no circumferential mesangial interposition (CMI), and these findings are different from MPGN. In this report we present a case of Takayasu arteritis associated with glomerulonephropathy mimicking MPGN.

DOI： 10.1007/s10067-004-0936-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa Healthcare  

We report the case of a 49-year-old man who presented with pneumatosis cystoides intestinalis associated with polymyositis and interstitial pneumonia. Three months after the administration of prednisolone and cyclosporine, he noticed mild abdominal distension, and a radiographic examination showed intraperitoneal free gas and intramural gas, suggestive of pneumatosis cystoides intestinalis (PCI). Additional treatment with a combination of doxycycline and high-dose oxygen therapy was effective in relieving the clinical symptoms and reducing the intramural gas. © Japan College of Rheumatology and Springer-Verlag Tokyo 2004.

DOI： 10.3109/s10165-004-0304-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa Healthcare  

We report the case of a 49-year-old man who presented with pneumatosis cystoides intestinalis associated with polymyositis and interstitial pneumonia. Three months after the administration of prednisolone and cyclosporine, he noticed mild abdominal distension, and a radiographic examination showed intraperitoneal free gas and intramural gas, suggestive of pneumatosis cystoides intestinalis (PCI). Additional treatment with a combination of doxycycline and high-dose oxygen therapy was effective in relieving the clinical symptoms and reducing the intramural gas. © Japan College of Rheumatology and Springer-Verlag Tokyo 2004.

DOI： 10.3109/s10165-004-0304-7

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Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vlL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto, rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing viL-10 (pCAGGS-vlL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vlL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGSvIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vlL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4(+) T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-gamma, tumor necrosis factor-a, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vlL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vlL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.

DOI： 10.1038/sj.gt.3301988

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Background: Leukocyte Fc receptors for immunoglobulin G (FcγR) play a major role in the handling of immune complexes and pathogens in systemic lupus erythematosus (SLE) and periodontitis. Both diseases have been shown to be partly influenced by genetic components including FcγR genotype. The aim of this study was therefore to evaluate whether FcγR gene polymorphisms are associated with periodontitis risk in SLE patients. Methods: The study subjects consisted of 42 SLE patients with periodontitis (SLE/P), 18 SLE patients without periodontitis (SLE/H), 42 healthy subjects with periodontitis (H/P), and 42 healthy subjects without periodontitis (H/H), who were all unrelated Japanese non-smokers. Genomic DNA was isolated from peripheral blood, and FcγR genotypes for 3 biallelic polymorphisms (FcγRIIa-R131/H131, FcγRIIIa-158V/158F, FcγRIIIb-NA1/NA2) were determined by allele-specific polymerase chain reactions. Results: The SLE/P group was found to have more mild levels of periodontal destruction than the H/P group (P &lt
0.01). There was a significant difference in the distribution of FcγRIIa genotypes between SLE/P and H/H groups (P = 0.004). A significant overrepresentation of the FcγRIIa-R131 allele was found in the SLE/P group compared to the H/H group (SLE/P versus H/H: odds ratio [OR] 3.13, 95% confidence interval [CI] 1.46-6.77, P = 0.0013). Furthermore, the prevalence of periodontitis was found to be 70% in SLE patients. The FcγRIIa-R131 allele was also found to be overrepresented in the SLE/P group compared to the SLE/H group (SLE/P versus SLE/H: OR 3.40, 95% CI 1.18-10.25, P = 0.011). Conclusion: These results show the FcγRIIa-R131 allele to be associated with periodontitis risk in SLE patient.

DOI： 10.1902/jop.2003.74.3.378

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We describe a rare case of a 46-year-old Japanese man with dermatomyositis (DM) and interstitial lung disease who developed spontaneous pneumomediastinum and subcutaneous emphysema. Relatively mild myositis, mild elevation of CK values and the absence of anti-Jo-1 antibody were observed and the case was similar to amyopathic DM. Treatment of this patient with oral prednisolone and cyclosporin A (CsA) was effective for the myositis and interstitial lung disease. The administration of CsA enabled rapid tapering of the dose of prednisolone without aggravating the disease. Pneumomediastinum and subcutaneous emphysema disappeared 5 months later without recurrence. The serum levels of KL-6 were monitored every 2 weeks to help determine whether this may have contributed to the recurrence of interstitial pneumonitis. This is a rare case of pneumomediastinum in a patient with DM.

DOI： 10.1007/s10067-002-0675-0

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In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients and cytokine levels measured. The serum levels of five cytokines (IL-1β, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly higher in all RA patients than in those with OA. Mean (±SD) IL-2 levels were significantly higher in patients with mutilans-type RA (309.8±686.3 pg/ml) than in patients with other types of RA (66.5±173.1 pg/ml
P &lt
0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of RA (P &lt
0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables were no different between mutilans RA and other types of RA. No correlations were observed between IL-1β, IL-2, IL-3, IL-6 and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related to systemic inflammation, as there was no correlation with other inflammatory factors.

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The aim of the study was to determine the frequency of amyloidosis detected by gastroduodenal biopsy in rheumatoid arthritis (RA) patients, and to investigate correlations between the results of gastroduodenal biopsy and abdominal fat and renal biopsies. A total of consecutive 1006 RA patients underwent gastroduodenal biopsy. The 71 patients who tested positive for gastrointestinal (GI) amyloidosis were asked to undergo renal and abdominal fat biopsies, and 21 did so. Renal biopsies were also performed on 12 patients with no amyloidosis but indicators of drug-induced renal damage, and abdominal fat biopsies were performed on 50 RA patients with no indication of amyloidosis. The prevalence of GI amyloidosis was 7.1%. Urinary abnormalities and GI symptoms were common in GI amyloidosis, and inflammatory markers were elevated. Sixty-one (86%) had either depressed creatinine clearance or urinary symptoms. Nineteen of the 21 patients (91%) with GI amyloidosis who underwent renal biopsies also had renal amyloid deposits. Eleven of the 21 (52%) had amyloidosis on abdominal fat biopsy. None of the 12 patients without GI amyloidosis had renal amyloidosis on renal biopsy, and none of the 50 patients without GI amyloidosis had amyloidosis on abdominal fat biopsy. Gastroduodenal biopsy reveals a high prevalence of amyloidosis in RA patients. Amyloidosis is often associated with signs of renal impairment. Results of GI biopsy are highly correlated with those of renal biopsy, but the results of fat biopsy are not. We recommend GI biopsy for RA patients for the screening of systemic amyloidosis.

DOI： 10.1007/PL00011217

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Language：Japanese   Publisher：(一社)日本透析医学会  

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To clarify the characteristics of renal haemodynamics and their correlation with renal pathology in patients with systemic lupus erythematosus (SLE), renal function and renal biopsy findings from 101 SLE patients were analysed retrospectively. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were examined simultaneously. Filtration fraction (FF) was calculated from the values obtained for GFR and RPF (GFR/RPF). The GFR was low in one-third and within normal limits in two-thirds of class IV patients with lupus nephritis (LN). In contrast, high RPF was observed in half of class IV patients. As a result, over 70% of class IV patients possessed a very low FF (less than 15%). The sensitivity of very low FF for class IV LN was significantly higher than that of low GFR. In conclusion, low FF was frequently recognized, especially in patients with diffuse proliferative LN. Decreased FF was a highly sensitive indicator of diffuse proliferative LN. Thus, determination of renal haemodynamics, including FF, may be a useful clinical parameter for evaluating renal involvement in patients with SLE.

DOI： 10.1046/j.1440-1797.2001.00034.x

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Objective. To clarify the clinical significance of anticentromere antibodies (ACA) in patients with systemic lupus erythematosus (SLE). Methods. Two hundred sixteen patients with SLE who were treated in our department were surveyed cross sectionally for the presence of ACA using indirect immunofluorescence on HEp-2 cell lines. ACA were identified by their discrete speckled pattern. Antibodies to the major centromere protein, CENP- B, were also studied with ELISA. Serial determinations of anti-CENP-B were carried out using stored serum samples, if available. Results. ACA were recognized in 12 (5.6%) patients with SLE. All patients were receiving steroid therapy, with a mean dose of prednisolone of 14.4 mg/day. These patients also tested positive for anti-CENP-B with high titers despite the low serological disease activity in most. Three or more CREST features were observed in 2 patients and 2 others had no such features. Both patients without CREST features had a relatively short disease duration. The age at onset of SLE was significantly higher and Raynaud's phenomenon was more frequent in patients with ACA than in patients without ACA. In 8 of 10 patients tested, retrospective analysis using stored sera revealed no consistent change in anti-CENP-B titers over time. Conclusion. The presence of ACA in patients with SLE is apparently more frequent than previously believed. Patients with SLE with ACA may be a distinct subgroup. A longterm followup is warranted to fully determine the clinical significance of ACA in patients with SLE.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ Publishing Group  

Objective - To clarify the characteristics of renal haemodynamics in patients with lupus nephritis (LN). Methods - The glomerular filtration rate (GFR) and renal plasma flow (RPF) of 37 patients with active LN were studied longitudinally over an interval of 8 to 144 weeks during treatment with corticosteroids or cytotoxic drugs, or both. All patients had clinical renal disorders and underwent renal biopsies. Results - Analysis of renal biopsy specimens showed that 31 patients had class IV LN. Class II, III, and V LN were present in two patients each. The average GFR increased significantly from 65.4 (SD 33.0) in the pretreatment stage to 86.6 (31.6) ml/min in the post-treatment stage, accompanied by an improvement in urinary or immunological abnormalities, or both. On the other hand, RPF decreased significantly from 625.2 (243.0) to 519.8 (179.0) ml/min. Therefore, the filtration fraction (FF) increased significantly from 10.7 (4.3)% to 16.8 (3.7)%. Low FF was recognised predominantly in patients with class IV LN, but was also observed in patients with other classes. The FF returned towards normal irrespective of the degree of GFR recovery. No significant changes were observed in the levels of blood pressure. Conclusion - A reduction in GFR out of proportion to the reduction in RPF as demonstrated by the low FF values was related to the severity of LN or disease activity, or both. Therefore, relative evaluation of GFR and RPF, namely the determination of FF, may be a useful clinical parameter to determine the status of LN.

DOI： 10.1136/ard.57.4.226

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Language：Japanese   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/naika.86.1351

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Objective - To clarify the characteristics and pathogenesis of renal disorders in patients with rheumatoid arthritis (RA). Methods - In this study, 143 patients with RA were included, from whom 43 with urinary abnormalities were biopsied. Serum rheumatoid factor (RF) concentrations of IgA and IgM isotypes were also measured in these patients by enzyme linked immunosorbent assay. Results - Light microscopy of renal biopsy specimens showed minor glomerular abnormalities in six patients, mesangial proliferative glomerulonephritis (GN) in 21, membranous nephropathy in seven, renal amyloidosis in seven, and tubulo-interstitial nephritis in two. Twelve patients with mesangial proliferative GN and one with minor glomerular abnormalities were found by immunofluorescence microscopy to have abnormalities consistent with IgA GN. Although the concentrations of IgA-RF in patients with IgA GN were slightly raised compared with those with glomerulopathy established by biopsy but not associated with IgA GN, the concentrations of IgA-RF were higher in patients with RA with vasculitis or interstitial pneumonia than those with RA complicated by IgA GN. Conclusions - Mesangial proliferative GN, including IgA GN, may be a frequent renal lesion in Japanese patients with RA. IgA-RF may play little pathogenetic part in the development of IgA GN in RA.

DOI： 10.1136/ard.55.8.520

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We evaluated the clinical value of the glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with systemic lupus erythematosus (SLE). All of the patients fulfilled the criteria for SLE of the American Rheumatism Association and were divided into two groups by the criteria for disease activity. GFR and RPF were simultaneously measured by the standard clearance technique using sodium thiosulfate and sodium paraaminohippurate, respectively. Ninety-six clinically active patients and 60 inactive patients underwent one clearance study. In 36 other patients, repeated clearance studies were undertaken on two occasions during the period from the active to inactive phase. The mean RPF was 590. 3± 213. 7 ml/min in 132 active patients and 485. 7±184. 0 ml/min in 96 patients without disease activity (p&lt
0. 01), whereas the mean GFR was comparable between the two groups. In active SLE, the mean GFR in 76 patients with proteinuria was 76. 0±38. 2 ml/min as compared with 104. 8±34. 3 ml/min in 56 patients without proteinuria (p&lt
0. 01)
however, there was no significant difference in the mean RPF between the two groups. A fall in GFR was frequently observed in patients with class IV lupus nephritis. In contrast, there was no significant difference in the mean RPF between class IV patients and the patients in the other classes. As a result, a marked decrease in the filtration fraction (FF) was frequently observed in class IV lupus nephritis, irrespective of the use of diuretics or antihypertensive agents. Semiquantitative histological analyses revealed that mesangial proliferative changes were more responsible than glomerular sclerotic changes for these hemodynamic features. In conclusion, a reduction in GFR out of proportion to that in RPF as evidenced by a remarkably low FF was likely to be related to the clinical disease activity and renal histological severity of SLE patients. Hence, relative evaluation of GFR and RPF, namely determination of FF, could be a useful clinical parameter to estimate the status of SLE patients. © 1994, Japanese Society of Nephrology. All rights reserved.

DOI： 10.14842/jpnjnephrol1959.36.1028

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Other Link： http://hdl.handle.net/10191/44332

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Other Link： http://hdl.handle.net/10191/44317

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Other Link： http://hdl.handle.net/10191/44316

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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Other Link： http://search.jamas.or.jp/link/ui/2015356131

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DOI： 10.3109/03009742.2011.569754

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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症例は70歳、女性。2005年に関節リウマチを発症し、プレドニゾロン、メトトレキサートによる治療を受けたが症状コントロール困難であった。2006年10月からタクロリムスを追加され、関節症状の改善を認めた。2007年2月末から咳嗽、喀痰、呼吸困難感、全身倦怠感が出現し、画像上両側肺野にground glass opacityを認めたため、メトトレキサート肺臓炎、ニューモシスチス肺炎を疑い、メトトレキサートとタクロリムスを中止し、メチルプレドニゾロン・パルス療法とTrimethoprim-sulfamethoxazole投与を行った。気管支肺胞洗浄液からニューモシスチスの嚢子が検出されニューモシスチス肺炎と診断した。関節リウマチに対してメトトレキサート、タクロリムスを使用する症例が近年増加しており、日和見感染のリスクが高まると考えられる。さらにメトトレキサートによる肺臓炎とニューモシスチス肺炎の鑑別も重要である。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2006106162

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Other Link： http://search.jamas.or.jp/link/ui/2005237396

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It is well known that amyloidosis is one of the critical complications which Influences the prognosis of patients with rheumatoid arthritis (RA). We studied seventy-six patients with definite or classical RA who were diagnosed as amyloidosis by biopsy. The average duration of RA prior to the diagnosis of amyloidosis was 15.4 ± 9.4 years. The average period from the diagnosis of amyloidosis to death was 67.4 months. High onset age of amyloidosis was the major factor deter-mining poor survival in these patients (P < 0.001). Additionally, the male gender played a major factor determining poor survival (P < 0.001) . Thirty-eight patients were treated with hemodialysis. Survival in dialysis at 9.8 months was 75 %, at 60.6 months was 50 %, and at 100.0 months was 25 %. Survival of amyloidosis patients without dialysis within the same period was better at 31.8 months with a survival rate of 75 % and at 66.7 months was 50 %, and the difference was not significant. The long-term results were sufficient to encourage us to initiate hemodialysis in patients with end stage renal disease due to reactive amyloidosis associated with RA.

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