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Antiplatelet therapy has been proposed as the treatment of choice for ischemia/reperfusion injury. The aim of this study is to elucidate the difference in effect between cilostazol (CZ) and acetylsalicylic acid (ASA) on microcirculatory disturbance in ischemia/reperfusion injury. Either 10 mg/kg of CZ (n = 14) or 100 mg/kg of ASA (n = 14) was administered orally to mice. Thereafter, 20 min of intestinal ischemia, followed by 60-min reperfusion, was applied; then, the status of submucosal microcirculation was observed under intravital microscopy. The blood cell counts and organ damage markers were examined in the portal blood. Next, 5 mm of the ileum was excised and was then histologically examined. Platelet-leukocyte aggregates were often observed in the postcapillary venules, and this formation was significantly reduced by both CZ and ASA. The number of adherent leukocytes was significantly lesser in the CZ-treated mice than in the ASA-treated mice (P < 0.01). The leukocyte number, lactate dehydrogenase, and lactate levels were best maintained in the CZ-treated mice (P < 0.05). The villus height was best preserved in the CZ-treated mice. Cilostazol inhibited not only the platelet aggregation but also the leukocyte adhesion to the endothelium, thereby inducing organ protection.

A parametric X-ray radiation (PXR) generator system was developed at the Laboratory for Electron Beam Research and Applications (LEBRA) at Nihon University; this PXR generator system is a tunable wavelength and quasi-monochromatic X-ray source constructed as one of the advanced applications of the LEBRA 125-MeV electron linear accelerator. The PXR beam which has characteristic of energy distribution. The theoretical values of energy distribution obtained at the output port were calculated to be approximately 300 eV and 2 keV at the central X-ray energies of 7 keV and 20 keV, respectively. In order to investigate the energy distribution, several measurements of the X-ray energy were carried out. The X-ray absorption of known materials and that of thin aluminum has been evaluated based on analyses of images taken using an imaging plate. The X-ray energy was deduced base on the identification of the absorption edges, and the energy distribution was estimated based on measurements using aluminum step method. In addition, an X-ray diffraction method using a perfect silicon crystal was employed, and spectra were measured using a solid state detector (SSD). The results of these experiments agreed with the calculated results. In particular, the well-defined absorption edges in the X-ray images and the typical rocking curves obtained by the measurement of the X-ray diffraction indicated that the distribution has a high-energy resolution.

This study investigated the potential benefits of combination therapy using antithrombin (AT) with danaparoid sodium (DA) compared with the use of AT with unfractionated heparin (UFH) in the treatment of sepsis.Rats infused with lipopolysaccharide were treated with either DA alone, AT alone, AT plus DA, AT plus UFH, or human serum albumin as controls. AT (125 U/kg) was injected into the AT group immediately after lipopolysaccharide infusion. The AT/DA and AT/UFH groups received the same dose of AT in conjunction with either DA (400 U/kg) or UFH (400 U/kg). The status of the mesenteric microcirculation was examined by intra-vital microscopy and the laboratory indices of coagulation, inflammation, and organ dysfunction were measured.The coagulation markers were improved following the administration of DA or UFH. The decreases in the WBC counts were significantly suppressed in the AT/DA group. The elevation of IL-6 decreased in the AT, DA, and AT/DA groups (all p0.01) but not in the AT/UFH group. The prostaglandin I2 levels were significantly elevated only in the AT/DA group (p0.05). The WBC adhesion was significantly suppressed in the DA, AT/UFH, and AT/DA groups (p0.05), and the RBC velocity was best maintained in the AT/DA group with no associated increase in capillary hemorrhage. The elevation of ALT and BUN significantly improved only in the AT/DA group. ONCLUSION: Organ dysfunction can thus be alleviated by even moderate doses of AT replacement when co-administered with DA.

Objective: Abnormalities in the vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of the study was to examine the effect of recombinant human activated protein C on leukocyte-endothelial interaction in endotoxemia. Design: Experimental animal model of sepsis. Setting: University research laboratory. Subjects: Normal Wistar rats. Each animal was infused with 4.5 mg/kg lipopolysaccharide to simulate severe sepsis. Interventions: Rats were injected with endotoxin simultaneously with either a low or a high dose of recombinant human activated protein C (n = 7). One, 2, and 3 hrs after injection, mesenteric microcirculation was observed under intravital microscopy. In another series, tumor necrosis factor, interleukin-6, alanine transaminase, and blood urea nitrogen levels were evaluated (n = 5). Measurements and Main Results: The adhesive leukocyte count on the endothelium was significantly suppressed in both high-dose and low-dose groups (p

目的:エンドトキシン血症における活性化プロテインC(APC)のサイトカイン産生,白血球接着調節作用を検証する。方法:ラットにAPCを投与した後にエンドトキシン(LPS)を投与するAPC群(n=12)と0.5%アルブミンをした後にLPSを投与するコントロール群(n=12)を設定し,1,3時間後に炎症性サイトカイン(各群n=5),1,2,3時間後に腸間膜細小静脈における接着白血球を算定した(各群n=7)。結果:tumor necrosis factor, interleukin-6, cytokine-induced neutrophil chemoattractantレベルはAPC群において有意に抑制された。一方monocyte chemoattractant protein-1には差がなかった。さらにAPC群では白血球接着が有意に抑制された(P

5'-Deoxy-5-fluorouridine (5'-DFUR) is a prodrug of 5-fluorouracil (5-FU), which is known to be converted by thymidine phosphorylase (dThdPase). A recent preclinical study revealed that cyclophosphamide (CPA) upregulated dThdPase activity, specifically in tumor cells. The purpose of the present study was to examine the efficacy of long-term administration of 5'-DFUR/CPA for patients with recurrent breast cancer.Fifteen breast cancer patients with recurrent tumors entered this study. Ten patients had bone metastasis, five had lung metastasis, and two had liver metastasis. Three patients had multiorgan metastases. All patients had had previous exposure to standard chemotherapy such as CAF (CPA, doxorubicin, and 5-FU) and CMF (CPA, methotrexate, and 5-FU). The patients were orally administered with daily doses of 5'-DFUR at 800-1200 mg and CPA at 200 mg for 2 weeks as induction therapy, followed by 2 weeks' rest (one to two cycles). Daily doses of 800 mg of 5'-DFUR and 100 mg of CPA (as maintenance therapy) were continuously administered thereafter. Ten of the 15 patients received the maintenance therapy alone. The treatment was continued for at least 24 months (average, 35.2 months).The main findings included a significant decrease in pain in nine patients with bone metastasis, and this effect continued for more than 2 years. As the pain decreased, the patients' quality of life (QOL) was improved. Liver metastasis was diminished in two out of two patients. Hematological toxicity of more than grade 3 was recognized in three patients, but only during the induction therapy.Oral administration of 5'-DFUR/CPA is well tolerated and useful for patients with recurrent breast cancer.

エンドトキシン誘発臓器障害に対する低用量(最大効果量の1/4)のアンチトロンビン(AT)とdanaparoid sodium (DS)併用の治療効果を評価した。[方法]ラットにlipopolysaccharide(LPS)を投与して敗血症モデルとし,治療群としてAT125U・kg-1を投与するAT群,DS400U・kg-1を投与するDS群,さらにATとDSを併用するAT/DS群を設定した。そして微小循環および凝固や臓器障害の指標を比較した。[結果]AT活性はAT/DS群で148%とその他の群と比較して有意に高値であった。凝固指標の改善はDS,AT/DS群で同等に認められた。白血球の接着抑制と白血球減少,血流速度の維持はAT/DS群で認められた(P

BACKGROUND The beneficial effects of antithrombin on endotoxemia are well known. The purpose of this study was to examine the effects of antithrombin in a supertoxin-induced sepsis. METHODS Mice were injected with staphylococcal enterotoxin B simultaneously with antithrombin. At 1 hour after injection, the mesenteric microcirculation was observed under intravital microscopy. In addition, humoral mediators were measured at the same time. RESULTS The number of rolling leukocytes on the endothelium was significantly reduced in the treated mice (p < 0.01). The decrease of white blood cell and platelet counts was significantly inhibited in the treated animals (p < 0.01 for both). A comparison of the intercellular adhesion molecule-1 (p < 0.05), soluble tumor necrosis factor-alpha receptor (p < 0.05), and interleukin-6 (p < 0.01) levels showed less increase in the treated mice. CONCLUSION Antithrombin showed a protective effects on the microcirculation of staphylococcal enterotoxin B-challenged mice by attenuating leukocyte-endothelial cell interaction. Suppression of adhesive molecule expression and cytokine production appears to play roles in this effect.

The closed-system transfer device (CSTD), which is used to prevent the exposure of medical staff to anticancer drugs, has been reported to allow safe preparation and administration of these drugs to patients. At many medical institutions, however, the use of such devices is limited to select anticancer drugs. This could be attributable to the longer preparation time compared to the conventional injection technique with a syringe and needle, as well as the fact that the anticancer drugs are too expensive to be covered by the remuneration available for medical services. Against this background, we measured the time required to prepare cyclophosphamide(CPA)and estimated the cost incurred. Our results indicated that the preparation time for either a single dose of 100 mg CPA or a combination of 100 mg CPA and 500 mg of another drug(100mg+500 mg group)was significantly longer than that for 500 mg of a single drug. On the other hand, use of a CSTD reduced the total cost (drug cost+CSTD cost)on switching to a single dose of 500 mg, resulting in a 5-year savings as follows: 3,755,217 yen for ChemoCLAVE®, 6,302,622 yen for PhaSeal®, and 2,698,451 yen for Chemosafe®. These findings suggest that the appropriate selection of drugs, including a large standard dose of CPA, allows shortened preparation time and reduced total drug cost as well as CSTD cost.

早期胃癌症例に対するD1+αリンパ節郭清を伴う腹腔鏡下幽門側胃切除術の手術侵襲度を, メディエータの推移から, 開腹による幽門側胃切除術と比較検討した. 対象は各群10例ずつで, Interleukin-6 (IL-6), Interleukin-10(IL-10)と好中球elastase(PMN-E)を術前から術後第3病日まで測定した. 結果, IL-6, IL-10の推移の比較では, 両群ともに術後軽度の上昇を示し群間で違いはみられなかった (IL-6: p=0.1, IL-10: p=0.78). PMN-E の推移の比較では, 腹腔鏡下幽門側胃切除術では術後の上昇が少なく, 開腹下幽門側胃切除術では継続的な上昇がみられその推移に違いがみられた (p=0.04).以上よりIL-6, IL-10は両群ともに上昇が少なく差が見られなかったが, PMN-E の推移の違いから腹腔鏡下幽門側胃切除術の開腹幽門側胃切除に対する低侵襲性が示唆された.

重症敗血症に対して行われるアンチトロンビンIII投与には,凝固機能抑制以外にも血管内皮機能調節やサイトカイン産生調節などが期待されている。今回われわれは,エンドトキシン投与ラットを用いてアンチトロンビンIII大量投与がサイトカイン産生に及ぼす影響を検証した。対象と方法:Wistar系ラットに中心静脈カテーテルを挿入してアンチトロンビンIII 250U/kgもしくは500U/kgをone-shotで静脈内に投与し,その30分後よりエンドトキシン5.0mg/kgを3時間かけて静脈内に持続投与した。そしてエンドトキシン投与終了6時間後に採血を行って血液生化学検査を行い,また投与終了後0hr, 3hr, 6hrの各時間における血中TNFα, IL-4, CINCレベルの測定を行った。結果と考察:AT-III 250, 500U/kgの投与により,AT-III活性はそれぞれ120%および170%程度を維持することが可能であった。そしていわゆるsupranormal levelに達したAT-III 500U/kg投与群においては血小板数の減少や,フィブリノーゲンの減少が有意に抑制された(各々p

重症敗血症に対して行われるアンチトロンビンIII (AT-III)投与には,凝固機能抑制以外にも血管内皮機能調節作用が期待されている。今回われわれは,エンドトキシン(LPS)投与ラットを用いて,AT-III大量投与が血管内皮細胞の血管作動因子産生に及ぼす影響を検討した。対象と方法:Wistarラットに中心静脈カテーテルを挿入して,翌日よりLPSを24時間かけて静脈内に持続投与し敗血症モデルとした。そして,これと同時にAT-III 250U/kgもしくは500U/kgを24時間静脈内に持続投与して,投与終了時における生存率,およびprostaglandin (PG)I2やendothelin-1を含む各種血中マーカーの測定を行った。なお,コントロールとしてAT-IIIの代わりに生理食塩水のみを投与する群も設定した。結果と考察:LPS 10.0mg/kg投与時のコントロール群の生存率は0%であったが,250U/kg投与群では50% (p

実際の敗血症に近いモデルとして作製した微量エンドトキシン持続投与モデルを用いて,アンチトロンビンIIIによる臓器障害予防効果を検討した。方法:ラットに中心静脈カテーテルを挿入し,LPS0.5mg/kgを24時間かけて投与した。そして生理食塩水のみを投与したコントロール群(n=4)とAT-III 20U/kg/hrをLPSと同時に24時間持続投与したAT3群(n=5), AT-III 500U/kgをLPS投与開始時に静脈内投与し,さらにAT-III 20U/kg/hrを24時間持続投与したAT3/AT3群(n=6), AT-III 20U/kg/hrとヘパリン10U/kg/hrを24時間持続投与したHep/AT3群(n=6)の4群を設定し,血液指標と組織所見の比較検討を行った。結果:血小板数はすべての群で減少がみられたが,各群間における有意差はなかった。AT-III活性,fibrinogen,臓器障害の指標としたBUN, ALTについてはAT-IIIによる治療群において有意な改善がみられたが,治療群間での有意差はみられなかった。また組織学的検討でもAT-III治療群においては腎における血栓形成や,肝における局所壊死が軽度である傾向がみられた。以上の結果から,AT-IIIは凝固機能抑制を行うことにより,敗血症において臓器保護効果を発揮しているものと考えられた。

プロテインCは血管内皮表面のトロンボモジュリンによって活性化される,ビタミンK依存性のタンパクで抗凝固,線溶活性化に中心的な役割を担っている。今回SIRSの基準を3日間以上連続して満たした30症例においてプロテインC活性の測定を行い,敗血症時の挙動に関して検討を行った。対象例のうち15例においては臓器障害がみられず(SIRS群),11例ではDIC以外の臓器障害の合併がみられた(MODS群)。また4例ではDICを含む多臓器障害の合併がみられた(DIC群)。MODS, DIC群におけるSIRS発症後第3日のPC活性は各々47.3±23.3%, 32.0±9.0%で,SIRS群における68.9±22.5%よりも有意に低下していた(各々p

Background This study was designed to determine whether 5-fluorouracil combined with intermittent low-dose cisplatin (cis-diaminedichloroplatinum, CDDP), a 5-fluorouracil modulator, would be an effective antitumor regimen.

敗血症性臓器障害の発生には好中球-血管内皮間の相互作用が重要な役割を果たしており,とくに好中球表面のインテグリンファミリーと血管内皮細胞表面のintercellular adhesion molecule-1(以下ICAM-1と略す)の結合が重要である。最近血中にみられる可溶性のICAM-1レベルが血管内皮表面のICAM-1発現量を反映するという報告がなされた。そこで今回,敗血症患者における血中の可溶性ICAM-1(以下sICAM-1と略す)レベルを測定し,臓器障害発生との関連を検討した。対象はsepsis induced SIRS 53例で,このうち40例は臓器障害を合併し,13例では臓器障害はみられなかった。そして臓器障害合併例のうち15例は多臓器不全のため死亡した。これらの症例において経時的に血中sICAM-1レベルの測定を行い,臓器障害合併例における臓器障害発生時のsICAM-1値と,非合併例における経過中sICAM-1最高値との比較を行った。またsICAM-1を測定したものと同一検体中のinterleukin-6 (IL-6)やpolymorphonuclear leukocyte elastase (PMN-E), thrombomodulin (TM), endothelin-1 (ET-1)の測定を行い,sICAM-1値との関連を検討した.その結果,臓器障害合併例におけるsICAM-1レベルは1,040.3±495.7ng/mlで,非合併例よりも有意に高値であった(p

脂肪は効率のよい栄養源でありながら,長鎖脂肪(LCT)は免疫機能抑制や肝障害などの副作用のため,重症敗血症時には一般的に使用禁忌とされている。今回われわれは完全静脈栄養(TPN)施行下のラット敗血症モデルにおいて,新しい脂肪製剤である中鎖脂肪(MCT)の有用性を検討した。方法:ラットを3日間絶食にした後に中心静脈カテーテルを留置し,輸液をブドウ糖とアミノ酸製剤のみで調製した無脂肪群と,非蛋白カロリーの50%をLCTで補給するLCT群,およびMCTで補給するMCT群の3群を設定した。そしてTPN施行後4日目に0.80あるいは0.05mg/kgのエンドトキシン(LPS)を静脈内投与し,24時間後の生存率を検討した。またLPS 0.05mg/kg投与時の血液生化学検査と腸間膜リンパ節,肝および動脈血培養における細菌コロニー数の検討も行った。結果:生存率はLPS 0.80mg/kg投与で無脂肪群50%, LCT群47%, MCT群83%, 0.05mg/kg投与で79%, 87%, 100%とそれぞれMCT群で最も高かった。血液検査ではLCT群で著明にみられた血小板数低下やGOT, GPTの上昇が,MCT群では軽度の変化にとどまっていた。また腸間膜リンパ節,肝および動脈血へのbacterial translocation (BT)は,MCT群が無脂肪群やLCT群に比し,同等もしくは低下傾向を示した。まとめ:敗血症ラットにおいてMCT投与群では無脂肪群やLCT群と比較して有意な死亡率の低下が得られた。そしてMCT群ではLCT群にみられるような血小板減少や肝障害がみられず,無脂肪群と同等かそれ以上の結果であったことから,MCT製剤は敗血症の治療に有用であると考えられた。

敗血症では比較的早期から過凝固状態が存在するが,これには単球/マクロファージや血管内皮細胞におけるtissue factor (TF)の表出による外因系凝固の活性化が考えられている。今回敗血症症例において血中のTFおよびその阻害作用を持つtissue factor pathway inhibitor (TFPI)の測定を行い,臓器障害やDICとの関連性を検討した。さらにインターロイキン6 (IL-6),好中球エラスターゼ(PMN-E),トロンボモジュリン(TM),エンドセリン1 (ET-1), thrombin antithrombin III complex (AT III), plasmin-α2 plasmin inhibitor complex (PIC)とTF, TFPIとの関係も検討した。対象はSIRSの基準を3日間以上連続して満たした敗血症38例で,このうち20例では臓器障害はみとめられず(SIRS群),10例はDIC以外の臓器障害を合併し(MODS群),8例はDICを含む多臓器障害を合併した(DIC群)。結果:DIC群におけるTFレベルは254.2±144.1pg/mlでMODS群やSIRS群よりも有意に高値であった。DIC群におけるTFPIも同様に,その他の群に比し有意に高値をとっていた。そして,TFは血管内皮の障害の指標であるTMやET-1と比較的高い相関を示したが,IL-6やPMN-E, TAT, PICとの間には相関はみられなかった。一方,TFPIではTMやET-1に加えIL-6やPMN-Eとの正相関もみられた。TF, TFPIとも凝固・線溶の指標したTAT, PICとの相関はみられなかった。結語:TFやTFPIは敗血症時に血管内皮の障害に伴って血中に放出され,DICのような内皮障害が高度である状態で高値を示すものと考えられた。しかしTFの分布はばらつきが大きく,TFPIは変動が軽度であるため重症度指標としての有用性には疑問が残った。

Docetaxel hydrate(DTX), a taxane anticancer drug, is known to be effective against a wide range of cancers, including breast cancer and non-small cell lung cancer. The DTX preparation Taxotere(2-vial DTX)has conventionally required dissolution in the attached solvent, while Onetaxotere(1-vial DTX), a newer product, is provided as a solution. This allows reduction of preparation time, so that improvement in operational efficiency can be expected. In this study, we measured the actual preparation time for 2-vial DTX and 1-vial DTX to compare their usefulness. The median preparation time for 2-vial DTX(n=84)and 1-vial DTX(n=84)was significantly different, with the respective values being 6. 52 minutes and 2. 67 minutes(p0. 01). By switching to 1-vial DTXfrom 2-vial DTX, which requires preparation of a premix solution with the attached solvent, the preparation procedure in daily practice becomes more convenient. This is because of a shorter preparation time as well as a lower risk of contamination, suggesting the usefulness of 1-vial DTX.

The fact that thrombomodulin (TM) is released into the bloodstream from damaged vascular endothelial cells led us to hypothesize that plasma levels of soluble TM could be an indicator of the development of organ failure. In this study, we examined the changes in plasma levels of TM in 60 septic patients and 13 postsurgical patients, and investigated the circulating levels of interleukin 6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E) to determine the mechanism causing the excess liberation of TM. The arterial ketone body ratio (AKBR) was also measured as an indicator of the hepatocyte energy state. Of the 60 septic patients, 26 developed organ failure, 10 of whom died. In contrast, none of the postsurgical patients developed organ failure. The mean plasma level of TM was significantly higher in the septic patients who developed organ failure compared to those without organ failure (P

目的:敗血症における凝固線溶機能の変動とその機序を検討する目的で,敗血症38例と,対照とした胃癌術後11例において,凝固線溶の鋭敏な指標であるthrombin-antithrombin III complex(以下TATと略す),plasmin-α2 plasmin inhibitor complex(以下PICと略す)と線溶系の調節因子であるplasminogen activator inhibitor-1(以下PAI-1と略す)の測定を行った。さらに,凝固線溶機能の変化と臓器不全発生の関連についても検討を行った。結果:敗血症時のTATの最高値は,臓器不全合併症例においては41.9±19.4ng/ml(mean±SD),臓器不全非合併症例では31.3±17.6ng/mlと,術後症例における31.2±12.9ng/mlと同程度の上昇で,凝固系には軽度の機能亢進が認められた。またPICの最高値は臓器不全合併例では1.78±1.49ng/ml,臓器不全非合併例では1.46±0.84ng/mlと,線溶機能は術後症例の2.03±2.05ng/mlよりもむしろ軽度の亢進状態であった。凝固線溶の状態はTATとPICのバランスで表されるが,敗血症性臓器不全合併例ではTAT/PICが57.0±43.8と臓器不全非合併例(26.6±16.5)や術後症例(24.6±16.1)に比べて2倍以上に上昇し,過凝固状態の存在が考えられた。そしてこの傾向は,とくに死亡した重症例で著明であった。TAT/PICの上昇機序に関しては,臓器不全合併例においてはPAI-1の有意な上昇が認められ,この上昇に応じてPICが低下する傾向がみられたことから,PAI-1の産生亢進が関与しているものと考えられた。結語:敗血症時には凝固系,線溶系ともに機能亢進状態にある。そして,敗血症性臓器不全時には両者のバランスであるTAT/PICレベルが上昇し,過凝固状態にあることが示された。さらに,この過凝固状態の発生機序としてはPAI-1の産生増加による線溶機能の抑制が考えられた。

Oxaliplatin (L-OHP), a platinum-containing antineoplastic agent, is a key drug for the treatment of colorectal cancer. However, it is often difficult to continue with its treatment because of the expression of allergic reactions. This study was an investigation of the expression of allergic reactions resulting from administration of L-OHP. A retrospective analysis was performed on patients undergoing therapeutic regimens including L-OHP, from April 2009 to November 2010 in Juntendo University Urayasu Hospital. The results showed that allergic reactions were expressed in 15 out of 81 patients (18. 5%). A high correlation was found between the time from administration until expression of the allergic reaction, and the number of treatment courses (r=-0. 521, p=0. 047). When patient characteristics were compared between the allergic reaction group and the no-reaction group, it was suggested that differences due to the regimen or the presence or absence of liver metastasis, which is considered to be related to drug metabolism, had no effect. Items showing significant differences were sexual difference(p=0. 022)and the effect of changes depending on the dose form of L-OHP(p=0. 003). It was possible to continue treatment with L-OHP in six patients even after expression of allergic reactions. Anti-allergy measures such as additional administration of steroids or antihistamines were suggested to be useful for continuing treatment.

重症敗血症時の臓器不全の発生には,凝固機能の亢進や血管内皮障害による微小血栓形成,組織循環障害が関与していると考えられているが,線溶機能に関しては明らかにされていない点も多い。今回敗血症時の線溶機能の変動を明らかにするため,systemic inflammatory response syndrome(以下SIRSと略す)の基準を満たす敗血症症例43例において,tissue plasminogen activator(以下t-PAと略す)とplasminogen activator inhibitor-1(以下PAI-1と略す)を測定し,臓器不全を合併した20例と臓器不全を合併しなかった23例の間で比較した。さらに血中interleukin 6(以下IL-6と略す),好中球エラスターゼ(以下PMN-Eと略す)やlactateとt-PAやPAI-1の関係についても検討を行った。その結果,血中PAI-1値は臓器不全を合併した群(540.1±435.3[mean±SDng/ml])が臓器不全を合併しなかった群(52.6±47.5)に比して有意に高値を示した(p

Postoperative intra-abdominal adhesion sometimes causes significant morbidity. The aim of this study was to compare the efficacy of our newly developed antiadhesive material, alginate flakes, to the most commonly used combination of hyaluronic acid and carboxymethyl cellulose film.Sodium alginate was formed into a gel, powder, or flakes. In the ex vivo study, these different alginate forms were attached onto pig skin and their antisolubility properties in saline and attachment stability were compared. In the in vivo study, a rat surgical adhesion model was used to study the properties of the alginates, and the rats were euthanized on day 14 after surgery. The efficacy of the antiadhesive materials was evaluated using an adhesion scoring system, and the locations that were treated with the antiadhesives were histologically examined.In the alginate groups, the alginate flakes were superior with respect to the antisolubility and the attachment stability ex vivo as well as with respect to the antiadhesive efficacy in vivo. The adhesion score was almost the same as that observed in the alginate flake and cellulose film groups.We developed an alginate flake material and demonstrated its antiadhesive effects both ex vivo and in vivo. This is the first reported study using this flake-like material, which has a unique characteristic in that it can be applied by spraying in compressed air. Alginate flakes may therefore be especially useful in the field of laparoscopic surgery.

A recent case of malignant fibrous histiocytoma arised in the male breast is reported with a review of the literaure. A 31-year-old man, who underwent resection for a tumor in the right breast 10 years before, again found a slightly enlarging, painless tumor 3×2 cm in size in the inside (D) region of the right breast. Excisional biopsy revealed grayish white tumor with a clear margin. Histologicaly, the tumor was composed of spindle shaped cells of a storiform pattern, which was diagnosed as malignant fibrous histiocytoma of the breast. Simple mastectomy was added to this patient. The tumor invaded the fat tissues. No postoperative adjuvant chemotherapy was given. The patient made an uneventful recovery and is now free of disease one year and two months the patient after surgery.

A 41-year-old woman was admitted to our hospital with the chief complaints of right lower abdominal pain andedema in the lower extermities. The diagnosis of gallstone disease associated with a retroperitoneal tumor of the infiltrated range was was made by using ultrasonography, computed tomography angiography. Primary tumor in the inferior vena cava or invasion of retroperitoneal tumor was suggested by postcavarography and magnetic resonanse imaging test. First of all, cholecystectomy was performed because of the complication of cholelithiasis. The tumor was a yellowish-white massive one with approx. 6 cm in diameter sitting to the lower surface of the liver, and internal and upper regions of the right kidney, and existed so as to eject from the inferior vena cava. The combined resection of the right kidney was performed, because resections of the partial postcaval walls and the tumor, and its ablastions were difficult. The double lineserial cross suture of the amputation stump of the inferior vena cava was carried out. The chemotherapy was concomitantly used as an auxotherapy. The postoperative couse was favorable, and the patient is under observation on ambulatory basis as of now progressed for 4 months. Eighteen cases of primary leiomyosarcoma in theinferior vena cava including this case have been reported in our country so faras we studied, and we also presented a discussion of some references because of its seldom occurrence.

We recently encountered a case of primary liposarcoma of the mammary grand, on the basis of which we conducted a review of the related literature. A 42-year-old female came to this department because of a painless tumor (3×3 cm) in her breast (AC). Various examinations failed to make a definite diagnosis. Excisional biopsy led to a diagnosis of liposarcoma. Modefied radical mastectomy was done followed by chemotherapy. A xanthochro-matic solid tumor (approximately 2.5 cm in diameter) was observed in the excisional biopsy specimen, histolgical examination revealed proliferation mainly of lipoblasts with irregular nuclei and fine granular fat in bullase. Although the excisional biopsy specimen obtained after modified radical mastectomy showed no malignant cells, chemotherapy using adriamycin and vincristine sulfate (ADR+VCR) was performed. Postoperative examination for distant dissemination disclosed no findings suggesting metastasis. One month has passed since the modified radical mastectomy, and there have been no signs relapse.

In order to study an availability of a new tumor marker BCA225, serum concentration of BCA225 was measured in 514 healthy individuals, and the baseline value was established from the resuruts. In 58 cases of primary breast carcinoma and 20 of recurrent breast carcinoma, BCA225, CEA, and CA15-3 were compared for the positive rate. Positive rate for BCA225 increased with a progression of the disease which was as high as 70% for recurrent breast carcinoma, Excepting breast carcinoma, BCA225 shoed the positive rate of 10.0% for various types of malignant diseases, 0.0% for benign breast tumors of the mammary gland, or 5.3% for benign breast tumors at othert sites, indicating that BCA225 was specific for breast carcinoma. In a combination assay using BCA225 and/or CEA, the highest positive rate was obtained in both primary and recurrent breast carcinoma in respect to the rerationship with the hormone receptors, the patient group which was negative for both ER and PR showed a high level of BCA225. Histologically the highest positive rate was found in solid carcinomas. A correlation between BCA225 and CA15-3 was observed, in which the condition of these antigens was discussed.

Damage to the lung microcirculation and alveoli caused by activated leukocytes is known to play an important role in the development of acute lung injury (ALI). The aim of this study is to evaluate the difference in the effect of pretreatment and posttreatment of a synthetic neutrophil elastase inhibitor sivelestat on ALI. Hamsters were instilled with 10.0 mg/kg of lipopolysaccharide (LPS) intratracheally for 1 h to simulate ALI. Two milligrams per kilogram of sivelestat was injected intraperitoneally either previously or after LPS infusion. One and 24 hours after the infusion of LPS, pulmonary microcirculation was observed under the intravital microscopy. In another series, the blood cell counts were evaluated. The adhesive leukocyte count on the endothelium was significantly lower in pretreatment group compared with control group (P < 0.01), whereas the difference was not significant in the posttreatment group. Similarly, the number of obstructed capillary was significantly lower in the pretreatment group (P < 0.01). The width of interstitium was significantly lower in the pretreatment and posttreatment group (P < 0.01 and 0.05, respectively). A comparison of white blood cell counts showed a better maintenance in pretreatment group (P < 0.05). Pretreatment of sivelestat demonstrated a protective effect on both intravascular and extravascular damage in the lung, whereas posttreatment only suppressed the latter damage.

It is well known that disorders of coagulation and fibrinolysis play a major role in the development of organ dysfunction during sepsis. Furthermore, the importance of the early initiation of anticoagulation therapy for severe cases has been emphasized based on the success of recent clinical trials. The purpose of this study is to search for useful markers for predicting organ dysfunction. Plasma samples were prospectively collected from 78 patients within 48 h after the onset of sepsis. Hemostatic markers and endothelial damage markers were compared between the patients with and without organ dysfunction. The WBC and platelet counts were not different between the groups. In contrast, fibrin/fibrinogen degradation products, D-dimer, thrombin-antithrombin complex, plasmin alpha2-antiplasmin complex, soluble fibrin, and total plasminogen activator inhibitor-1 were significantly higher, and the antithrombin activity and protein C levels were lower in the patients with organ dysfunction. Thus, the changes in the hemostatic molecular markers were associated with organ dysfunction from an early stage of sepsis, and antithrombin and protein C activities were found to be the most reliable markers.

The inflammatory response in severe sepsis is integrally linked to procoagulant activity and endothelial activation. The abnormalities in the microcirculation results in the development of septic organ dysfunction. The natural anticoagulant activated protein C is expected not only to improve the unbalanced coagulation/fibrinolysis system, but also to modulate the endothelial function, and to express the anti-inflammatory properties. To certify these effects, a large scale, multiple center, randomized, placebo controlled phase 3 trial (PROWESS trial) has been conducted. The results showed the statistically significant improved survival in patients with sepsis induced organ dysfunction (absolute risk reduction in 6.1%). As a result, activated protein C is recommended in patients at high risk of death such as Acute Physiology and Chronic Health Evaluation IIor = 25. However, since bleeding risk is reported as an adverse effect, activated protein C is contraindicated in patients with bleeding tendency.

Leucovorin (LV)/5-fluorouracil combination is one of the first-line forms of chemotherapy for colorectal cancer, and in this regimen it was recommended that 5-FU be infused continuously from the venous route. However, since this regimen limits the patients' ADL, oral administration is preferable. The purpose of this study is to elucidate the mechanisms of orally-administered LV/5-FU.The Gastrostomy was performed, and 1 x 10(6) of colon 26 was transplanted subcutaneously in CDF1 mice. In the continuous administration group, either 10, 20, 40 mg/kg of 5-FU and 100 mg/kg of LV were continuously infused for 7 days following gastrostomy using a microinfusion pump (n = 6). In the single infusion group, either 10, 20, 40 mg/kg of 5-FU was infused once a day for 7 days after gastrostomy concomitant with LV (n = 6). The other 6 animals served as the control, and LV alone was infused in this group. Tumor volume, thymidylate synthase inhibition rate (TSIR), incorporation of 5-FU into RNA (F-RNA) and body weight were measured at the end of the treatment. During the experimental period, mice were given free access to chow and water.The tumor volume suppression rate was significantly higher along with the amount of 5-FU. However, there was no significant difference between continuous and single infusion groups. TSIR was higher in the continuous group at the dose of 20 and 40 mg/kg. In contrast, F-RNA was higher in the single group at the dose of 20 and 40 mg/kg. Significant body weight loss was not recognized in any group.From these data, single administration of 5-FU is more effective for RNA dysfunction. On the other hand, continuous infusion is more damaging to DNA duplication. In summary, since the mechanism of the antitumor effect differs with the administration method, it is important to understand this mechanism.

Laparoscopy-assisted low anterior resection (LAR) for low rectal cancer is a difficult procedure, presenting problems with rectal washout, selecting the appropriate distal transection line, and achieving safe anastomosis. To resolve these problems, we used a prolapsing technique to perform laparoscopy-assisted LAR. Total mesorectal excision (TME) is performed laparoscopically. The proximal colon is transected laparoscopically with the aid of an endoscopic stapler, and the distal rectum, including the lesion, are everted and pulled transanally to outside the body. Only washout of and wiping off the distal rectum and intestinal resection are performed extracorporeally. The distal rectum is pushed back through the anus into the pelvis, and intracorporeal anastomosis is completed laparoscopically with a double-stapling technique. Our limited experience suggests that the prolapsing technique helps to prevent problems with laparoscopy-assisted LAR in selected patients with low rectal cancer.

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic formation of microthrombi and fibrin deposition in the vasculature. Cancer is one of the leading cause of DIC, which often complicates bleeding tendency and organ dysfunction. Even though DIC therapy is expectant, it is still important, since the bleeding tendency limits the quality of patients' life remarkably. Heparin, low molecular weight heparin, danaparoid, protease inhibitors for coagulation factors and antithrombin III are the choices for DIC. However, since the selection of the drugs is different depending on the basal disease, it is important to understand the pathophysiology of the individual situation. In general, protease inhibitors is recommended for 'fibrinolysis dominant DIC' like DIC associated with leukemia and terminal stage solid cancer, in contrast, danaparoid and antithrombin III are the first choice for 'coagulation dominant DIC' like sepsis. Supplement of concentrated platelets and fresh frozen should be limited for the patients whose primary disease can be controlled.