Authorship：Lead author   Publisher：克誠堂出版  

DOI： 10.18916/masui.2024120009

CiNii Research

Authorship：Lead author   Language：Japanese   Publisher：克誠堂出版(株)  

＜文献概要＞開口障害は,喉頭展開や気管挿管困難の危険因子となり,術前の重要な気道評価項目である。われわれは全身麻酔導入後に開口障害が増悪し手術中止となった症例に対し,全身麻酔導入前に歯科用バイトブロックを用いて最大開口位を維持し,安全に経口挿管および手術を施行することができた。

Authorship：Lead author   Language：Japanese   Publisher：日本臨床麻酔学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：Japanese   Publisher：(株)先端医学社  

核内に存在し長いDNAを核内に収納する役割をもつヒストンは、発生、分化、細胞運命の維持において重要な役割を担っている。しかし、ヒストンがいったん細胞外に放出されると、さまざまな生体反応を惹起し、とくに敗血症において主要なメディエーターとなることが報告されている。敗血症や外傷などにおいて、ヒストンを抑制する生体内物質や治療薬を有効に活用することが、新しい治療戦略につながる可能性がある。(著者抄録)

Authorship：Lead author   Language：Japanese   Publisher：医学図書出版(株)  

敗血症は外来微生物に対する過剰な全身性の炎症反応である。さまざまな炎症性メディエータの放出により惹起される過剰な免疫反応は、ショック、多臓器不全を誘発し、場合によっては致死的となる。そこで、この総説では、敗血症の病態を悪化させ予後に大きな影響を与える心筋障害、呼吸不全、免疫不全に関して概説する。敗血症性ショックにおける心機能障害のメカニズムには、β受容体のダウンレギュレーション、シグナル伝達系の異常、筋小胞体からのCa2+の放出障害、ミトコンドリアの傷害などが報告されている。敗血症において、接着分子やケモカインは、肺に好中球を捕捉し、活性化することでARDSを発症する。敗血症患者の多くは、初期の過剰な炎症期を乗り切るが、遷延するに伴い免疫抑制状態に陥り予後が悪化する。患者の免疫能を高めることで、病原体に打ち勝ち、新規感染の発症が予防できるため、臓器不全の回避、生存率の向上が期待できるのかもしれない。(著者抄録)

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM). rTM has been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive thromboembolism associated with consumptive coagulopathy, which is diagnostically indistinguishable from DIC. rTM binds to histones and neutralizes the prothrombotic action of histones. This may contribute to the effectiveness of rTM against DIC.

DOI： 10.1371/journal.pone.0075961

PubMed

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：Japanese  

CiNii Research

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

播種性血管内凝固症候群(disseminated intravascular coagulation、DIC)に対する遺伝子組換え型ヒトトロンボモジュリン製剤(recombinant human soluble TM、rTM)の併用効果を評価するため、敗血症性DIC症例のうち従来の治療にrTMを併用した17症例(投与群)と、併用しなかった16症例(非投与群)を対象に、止血凝固・線溶系、血管内皮細胞傷害、臓器不全の変化、90日後の死亡率に関して後ろ向きに検討した。投与群では、第1病日と比較して第7病日の可溶性フィブリン(P=0.039)、E-セレクチン(P=0.044)、旧厚生省DIC診断基準スコア(P=0.017)やSequential Organ Failure Assessment(SOFA)スコア(P=0.030)に有意な低下が認められた。一方、非投与群では有意な変化を認めなかった。第7病日のplasminogen activator inhibitor-1(PAI-1)は、2群間の比較検討において非投与群に比べて投与群で有意に低いことが示された(P=0.025)。生存分析では有意差は認めなかったが、投与群で90日後の予後改善傾向が示された(P=0.064)。今回の結果より、rTMの併用療法は敗血症性DICに対し有効な治療法になる可能性が示唆された。(著者抄録)

Authorship：Lead author   Language：Japanese   Publisher：(株)へるす出版  

Authorship：Lead author   Language：Japanese   Publisher：(株)へるす出版  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

患者は5歳の男児。発熱、嘔吐、痙攣が出現したため近医へ救急搬送され、抗痙攣薬投与、気管挿管後に、新型インフルエンザ脳症の診断にて当院へ紹介搬送された。ICUにて鎮静下に人工呼吸管理、および脳浮腫に対する治療を開始した。その後痙攣はみられず、第7病日、デクスメデトミジンのみ投与しながら覚醒させ抜管した。しかし、抜管直後より上気道狭窄音、陥没呼吸、努力性呼吸、頻呼吸を認めたため、ヘルメット型マスクCASTER"R"小児用を装着し非侵襲的陽圧換気(noninvasive positive pressure ventilation、NPPV)を開始したところ、呼吸状態はすぐに改善した。エア・リークはほとんど認めなかった。患児が嫌がる様子はなく、意志疎通も可能であり、声もはっきりと聞き取れた。翌日NPPVから離脱でき、再挿管を回避できた。ヘルメット型マスクは圧迫感がなく、小児でも受容性が高いため、小児にNPPVを施行する際に有用なデバイスとなることが示唆された。(著者抄録)

Authorship：Lead author   Language：Japanese   Publisher：The Japanese Society of Intensive Care Medicine  

A 5-year-old child suffering from fever, vomiting and convulsions was transported to an emergency medical center. He was administered anticonvulsant and performed tracheal intubation. A diagnosis of acute encephalopathy caused by 2009 influenza A (H1N1) was made, and the child was admitted to our hospital. He was admitted to the ICU and initiated on mechanical ventilation under sedation and treatment of brain edema. After that he never had convulsions. On hospital day 7, he woke up under administration of only dexmedetomidine, and extubation was performed. However, thereafter, the child developed stridor suggestive of upper airway stenosis, labored breathing with intercostal retraction, and tachypnea. Therefore, noninvasive positive pressure ventilation (NPPV) was initiated using a helmet (CASTER “R” for children). There was little air leak, and the respiratory condition showed prompt improvement. There were no problems with the use of helmet NPPV, and we could communicate successfully with the child and hear his voice. The following day, he could be weaned off from the NPPV, and re-intubation could be avoided. These findings suggest that the helmet may be a useful device for NPPV in children, because it doesn't appear to give rise to a feeling of suffocation, and has high acceptability even among children.

DOI： 10.3918/jsicm.18.95

CiNii Research

Authorship：Lead author   Language：Japanese   Publisher：The Japanese Society of Intensive Care Medicine  

To assess the combination effect of a genetic recombinant human soluble thrombomodulin (rTM) with conventional therapy on the treatment of disseminated intravascular coagulation (DIC), we conducted a comparative retrospective study of coagulation fibrinolysis, vascular endothelial damage, organ damage and mortality rate after 90 days among 17 patients with septic DIC treated with combination of rTM with conventional therapy (rTM group) and 16 patients treated with conventional therapy alone (non-rTM group). In the rTM group, a comparison between findings obtained on day 1 and day 7 of administration showed statistically significant decreases in the levels of soluble fibrin (<I>P</I> = 0.039) and E-selectin (<I>P</I> = 0.044), the DIC score (<I>P</I> = 0.017) and the Sequential Organ Failure Assessment (SOFA) score (<I>P</I> = 0.03), which were used to evaluate therapeutic efficacy, but no significant decreases were observed in the non-rTM group. On day 7 of administration, the plasminogen activator inhibitor-1 (PAI-1) level in the patients treated with the rTM was significantly lower than in the untreated patients (<I>P</I> = 0.025). A survival analysis did not show a significant difference between the two groups, but the results suggested a tendency toward a higher survival rate in the rTM group (<I>P</I> = 0.064). The results of our study suggested that treatment of combination of rTM with conventional therapy may have yielded considerable benefits to the treatment of septic DIC.

DOI： 10.3918/jsicm.18.583

CiNii Research

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

接着分子の一つであるE-セレクチンと臓器障害との関連を調べるため、ICU入室時に全身性炎症反応症候群(systemic inflammatory response syndrome、SIRS)の診断基準を満たし人工呼吸管理を要した52例を対象に、ICU入室24時間以内の可溶性E-セレクチン値とSequential Organ Failure Assessment(SOFA)スコアおよび各臓器別障害との相関関係を後ろ向きに検討した。可溶性E-セレクチン値とSOFAスコアとの間には有意な相関関係が認められ(P=0.0024)、各臓器別検討では呼吸障害(P/F ratio)(r=0.511、P<0.0001)に有意な相関が認められた。一方、acute lung injury/acute respiratory distress syndrome(ALI/ARDS)の病態識別能に関して、可溶性E-セレクチン、白血球数、CRP、顆粒球エラスターゼによるフィブリン分解産物(elastase digests of cross-linked fibrin、E-XDP)を検討したところ、可溶性E-セレクチンが肺障害に対して感度・特異度とも高いことが示された。以上の結果より、SIRS症例の肺障害発症に関して、接着分子の一つであるE-セレクチンが深く関与している可能性が示唆された。(著者抄録)

Authorship：Lead author   Language：Japanese   Publisher：(株)へるす出版  

Authorship：Lead author   Language：Japanese   Publisher：日本循環制御医学会  

Authorship：Lead author   Language：Japanese   Publisher：(株)へるす出版  

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本集中治療医学会  

Authorship：Lead author   Language：Japanese   Publisher：The Japanese Society of Intensive Care Medicine  

<B>Objectives:</B> A retrospective observational study was conducted to evaluate whether the plasma level of soluble E-selectin, one of the adhesion molecules, might be related to organ dysfunction in patients with systemic inflammatory response syndrome (SIRS). <B>Methods:</B> The data of 52 patients admitted to the ICU with SIRS and initiated on mechanical ventilation were retrospectively evaluated. <B>Results:</B> The plasma levels of soluble E-selectin determined within 24 hours of admission to the ICU were significantly correlated with the Sequential Organ Failure Assessment (SOFA) scores. Furthermore, the scores for respiratory dysfunction (evaluated by the P/F ratio) in the SOFA scoring system were also significantly correlated with the plasma levels of soluble E-selectin. In relation to respiratory dysfunction, the plasma levels of soluble E-selectin were higher in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) than in the non-ALI/ARDS patients, and a receiver operating characteristic (ROC) analysis revealed that this parameter might be a specific marker of ALI/ARDS. <B>Conclusions:</B> E-selectin, one of the adhesion molecules, might be closely related to the occurrence of respiratory dysfunction in patients with SIRS.

DOI： 10.3918/jsicm.17.491

CiNii Research

Authorship：Lead author   Language：Japanese   Publisher：(一社)日本救急医学会  

Authorship：Lead author   Language：Japanese  

CiNii Research

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

BACKGROUND: Nuclear histone proteins are released into the extracellular space during sepsis and act as major mediators of death. However, circulating histone levels have not been precisely quantified. METHODS: We developed a novel enzyme-linked immunosorbent assay (ELISA) for detection of circulating histone H3 levels and evaluated its performance. Using the ELISA, we measured plasma histone H3 levels in C57BL/6 J mice subjected to cecal ligation and puncture (CLP)-induced sepsis. RESULTS: The newly developed ELISA enabled reproducible measurement of histone H3 levels with a working range up to 250 ng/mL. Using the ELISA, we found that plasma histone H3 levels were elevated in septic mice compared with sham-operated mice (p < 0.01). The elevation of histone H3 levels was abrogated when neutrophils were depleted (p < 0.01). CONCLUSIONS: Our novel ELISA provides reproducible measurements of histone H3 levels. Circulating histone H3 levels are increased in septic mice in a neutrophil-dependent manner. Further studies are needed to evaluate the clinical utility of histone H3 levels in patients with sepsis.

DOI： 10.1186/s40560-018-0348-y

PubMed

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

UNLABELLED: The aim of the present study was to investigate whether changes in hepatic oxygenation can be detected by time-resolved spectroscopy (TRS) placed on the skin surface above the liver. METHODS: With approval of the local Hospital Ethics Committee and informed consent, six healthy volunteers aged 28.8 (25-36) years, and five patients with chronic renal failure aged 70.6 (58-81) years were studied. In six healthy volunteers, following echography, TRS (TRS-10, Hamamatsu Photonics K.K., Hamamatsu, Japan) probes consisting of a near-infrared light (at 760, 800, 835 nm) emitter and a receiver optode, were placed 4 cm apart on the abdominal skin surface above the liver or at least 10 cm distant from the liver. In five patients with chronic renal failure, following echography, TRS probes were placed 4 cm apart on the skin surface above the liver during hemodialysis (HD). RESULTS: In six healthy volunteers, the values of abdominal total hemoglobin concentration (tHb) were significantly higher in the liver area than in the other area (80.6±26.81 vs 44.6±23.1 μM, p=0.0017), while the value of abdominal SO2 in the liver area was nearly the same as that in the other area (71.5±3.6 vs 73.6±4.6%, p=0.19). The values of mean optical pathlength and scattering coefficient (μ's) at 800 nm in the liver area were significantly different from those in the other area (21.3±4.9 vs 29.2±5 cm, p=0.0004, and 7.97±1.14 vs 9.02±0.51 cm(-1), p=0.015). One of five patients with chronic renal failure complained of severe abdominal pain during HD, and abdominal SO2 decreased from 53 to 22%; however, pain relief occurred following cessation of HD, and SO2 recovered to the baseline level. CONCLUSIONS: Our data suggest that the optical properties of the liver may be measured by the TRS placed on the skin surface, and the hepatic oxygenation may act as a non-invasive monitoring for early detection of intestinal ischemia.

DOI： 10.1007/978-1-4939-3023-4_51

PubMed

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

Sepsis is aggravated by an inappropriate immune response to invading microorganisms, which occasionally leads to multiple organ failure. Several lines of evidence suggest that the ventricular myocardium is depressed during sepsis with features of diastolic dysfunction. Potential candidates responsible for septic cardiomyopathy include pathogen-associated molecular patterns (PAMPs), cytokines, and nitric oxide. Extracellular histones and high-mobility group box 1 that function as endogenous damage-associated molecular patterns (DAMPs) also contribute to the myocardial dysfunction associated with sepsis. If untreated, persistent shock causes cellular injury and the liberation of further DAMPs. Like PAMPs, DAMPs have the potential to activate inflammation, creating a vicious circle. Early infection control with adequate antibiotic care is important during septic shock to decrease PAMPs arising from invasive microorganisms. Early aggressive fluid resuscitation as well as the administration of vasopressors and inotropes is also important to reduce DAMPs generated by damaged cells although excessive volume loading, and prolonged administration of catecholamines might be harmful. This review delineates some features of septic myocardial dysfunction, assesses its most common underlying mechanisms, and briefly outlines current therapeutic strategies and potential future approaches.

DOI： 10.1186/s40560-016-0148-1

PubMed

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

DOI： 10.4236/ojanes.2015.59036

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

DOI： 10.4236/ojanes.2015.57028

Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publisher：日本臨床麻酔学会  

Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publisher：日本臨床麻酔学会  

Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publisher：(株)先端医学社  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J05887&link_issn=&doc_id=20131209420004&doc_link_id=%2Fae6thmed%2F2013%2F000304%2F005%2F0329-0333%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6thmed%2F2013%2F000304%2F005%2F0329-0333%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publisher：(一社)日本集中治療医学会  

Language：Japanese   Publisher：(一社)日本救急医学会  

Language：Japanese   Publisher：体液・代謝管理研究会  

Language：Japanese   Publisher：体液・代謝管理研究会  

Language：Japanese   Publisher：(株)シービーアール  

Language：Japanese   Publisher：(一社)日本脈管学会  

Event date： 2016.2

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Venue：神戸国際展示場、神戸ポートピアホテル  

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国際学会

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国内学会

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国際学会

Event date： 2014.9

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国内学会

Event date： 2014.7

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Venue：東京  

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Event date： 2014.6

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Venue：イギリス  

国際学会

Event date： 2014.5

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Venue：神奈川  

国内学会

Event date： 2014.3

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Venue：京都  

国内学会

Event date： 2013.9

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国内学会

Event date： 2013.6

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国際学会

Event date： 2013.5

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Venue：北海道  

国内学会

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Venue：鹿児島  

研究会

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