論文

85歳女。3年の血液透析歴があり、透析中に嘔吐・吐血を認め、上部消化管内視鏡検査で出血性胃潰瘍を認めた。その後、腹部膨満が出現し、腹部CTにてイレウス所見を認めた。以後、水様性下痢便が出現・持続し、4週間後に施行した腹部CTにて大腸の拡張、直腸壁の肥厚を認め、下部消化管内視鏡検査を施行した。肉眼的所見より潰瘍性大腸炎と診断し、プレドニゾロン40mg/日を点滴静注したが症状は改善せず、全身状態悪化し永眠した。剖検での病理組織学的所見で結腸粘膜筋板、粘膜下層および漿膜下層の小血管にアミロイド沈着を認めた。アミロイドはAA蛋白と同定され、全身性AAアミロイドーシスと診断された。

67歳男.糖尿病に対するインスリン注射のコンプライアンスが不良で,低血糖発作を頻回に起こしていた.風呂桶に水没しているのを発見され,救急隊到着時の心電図は心静止で,来院5分後に気管挿管を施行した.エピネフリン1mgを3分毎に計12回静注し,血糖値が簡易測定器で感度以下であったため40%ブドウ糖を静脈注射した.CPRを継続したが心静止が持続し,病着から50分後に死亡を確認した.途中で経鼻胃管を挿入し,血性成分を含む排液を認め,腹部レントゲンで胃内に大量のガスを認めた.気管挿管に際しては,まず聴診を行い,胸部および心窩部のいずれでも微弱な音を聴取した.バルブタイプの食道挿管検知器を装着したところ,圧縮した吸引用バルブを気管チューブに接続してもバルブが膨らまず,吸引が維持された.この段階で食道挿管を疑ったが,定量的呼気終末CO2モニターで呼気中にCO2を検出し,気管内への挿管を確認した.胸部X線では気管内に留置された挿管チューブと,溺水によると思われる非心原性肺水腫の所見を認めた

© 2019 The Author(s). Background: Programmed cell death 1 inhibitors have revolutionized therapy for cancer by their outstanding effectiveness. However, they may cause adverse effects, among which inflammatory myopathy is one of the most disabling. To elucidate its mechanism, we analysed muscle biopsies and compared them with other inflammatory myopathies. Methods: Muscle biopsies from three patients with inflammatory myopathy after treatment with PD-1 inhibitors for cancer were subjected to immunohistochemical and ultrastructural analyses to localize CD8+ cytotoxic cells and markers of lymphoid follicles. For comparison, two cases of polymyositis and one of juvenile dermatomyositis were examined. Results: Nearly identical pathological features were observed in the three cases. In the island-like foci of inflammation, muscle fibers were undergoing degeneration. CD8+ cytotoxic T cells, macrophages, CD4+ cells, and B cells were observed in the foci. CD8+ cells were seen outside and inside the basal lamina of non-necrotic muscle fibers. Lymphoid follicle-like structures with CD21+ follicular dendritic cells were present. The blood vessels in the foci showed features consistent with the high endothelial venules, on which their markers, PNAd and CCL21, were expressed. In polymyositis, blood vessels stained only faintly for PNAd and CCL21, while in juvenile dermatomyositis, in which tertiary lymphoid follicle-like structure was reported in the past, they stained positively. Conclusions: In inflammatory myopathy associated with PD-1 inhibitors, CD8+ cells appear to predominantly destruct muscle fibers. The presence of lymphoid follicle-like structures and expression of PNAd and CCL21 on the endothelial cells suggest the tertiary lymphoid organs are formed, and involved in the leakage of lymphocytes. Thus, in the three cases examined, formation of the tertiary lymphoid organs is likely to play an important role in genesis of the PD-1 myopathy.

Objective: The fused in sarcoma/translated in liposarcoma (FUS/TLS) protein was recently identified as a cause of familial amyotrophic lateral sclerosis (ALS), as well as a major component of the inclusion bodies found in subtypes of frontotemporal lobar degeneration (FTLD). These diseases now are collectively known as the novel clinical spectrum, FUS proteinopathy. ALS-linked mutations of FUS are clustered in the C-terminal region; however, the molecular properties of mutant FUS remain unclear. To gain insight into the pathogenesis of FUS proteinopathy, we examined the biochemical and cellular characteristics of mutant FUS in expressing cells. Methods and Results: Expression of ALS-linked FUS mutations resulted in their assembly into cytoplasmic stress granules (SGs), cellular structures that package mRNA and RNA-binding proteins during cell stress. A deletion mutant series revealed that the C-terminal region in FUS is critical for nuclear retention via Ran guanosine triphosphatase-dependent transport machinery. A parallel study of subcellular distribution revealed that ALS-linked mutants additively disturb the function of the C-terminus for nuclear traffic, resulting in cytoplasmic accumulation and the formation of SGs. Interpretation: This study demonstrates that mutant FUS, which is missing the nuclear traffic activity of the C-terminus, is dislocated to cytoplasm and assembled into SGs, indicating that disruption of translational regulation and metabolism of mRNA via inappropriate/excessive SGs may be crucial for FUS proteinopathies. Our findings provide new biological and pathological insights into the FUS protein that should help our understanding of the pathogenesis of ALS/FTLD. © 2011 American Neurological Association.

© 2017 American Headache Society Background: It is commonly known that headaches are induced by intake of specific food, drink, and/or additive. In addition, some patients experience postprandial headache independent of ingestion of specific items. Currently, information on the pathophysiology underlying this particular type of headache is scarce. Case reports: We report two cases in which headaches were observed after each meal. Postprandial hypotension was demonstrated in both cases. Tonometry-based continuous blood pressure measurement during head-up tilt revealed sympathetic dysfunction. In one patient, meta-iodobenzylguanidine (MIBG) myocardial scintigraphy detected cardiac sympathetic denervation, and diagnosis of pure autonomic failure was made. In both cases, treatment of postprandial hypotension was effective in relieving postprandial headache. Discussion: The possibility of postprandial hypotension should be explored in patients with headache that occurs after meal. To this end, tonometry-based blood pressure measurement and MIBG myocardial scintigraphy may be useful diagnostic investigations. Treating postprandial hypotension may be effective in alleviating the symptoms.

目的:虚血性脳血管障害の慢性期再発予防には、スタチンによる脂質プロファイルの改善が有用であることが知られている。スタチンの脳梗塞再発予防効果として血管内皮機能の改善を評価した。対象と方法:脳卒中専門外来を受診した虚血性脳血管障害慢性期症例およびハイリスク症例を対象に血流介在血管拡張反応(FMD)を施行した。このうち、高コレステロール血症を有し新たにロスバスタチン5mgを投与した症例については、投与後にFMDを行い前値と比較した。結果:病型別には、心原性塞栓症に比較して、ラクナ梗塞(p=0.02)およびアテローム血栓性脳梗塞(p=0.009)で有意に%FMDが低値であった。リスク別には、脂質異常症あり群はなし群と比較して有意に%FMDが低値であった(p=0.05)が、高血圧、糖尿病と%FMDに相関は認めなかった。ロスバスタチン5mgを投与した15例のうち内服前に%FMDがすでに良好であった症例を除いた11例では、ロスバスタチン投与後に%FMDは有意に改善した(p=0.04)。考察:FMDは脳梗塞の病型別、リスク別の血管内皮障害の程度を鋭敏に評価できる検査であることが改めて示された。ロスバスタチンはこの血管内皮機能を改善することが明らかとなり、脳梗塞予防効果の一機序である可能性が示唆された。(著者抄録)