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CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal

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IMMUNITY 2000年第4期13卷 453-462页

作者： Schulz, O Edwards, AD Schito, M Aliberti, J Manickasingham, S Sher, A Sousa, CRE Imperial Canc Res Fund Immunobiol Lab London WC2A 3PX England NIAID Parasit Dis Lab Immunobiol Sect NIH Bethesda MD 20892 USA

CD40 ligation triggers IL-12 production by dendritic cells (DC) in vitro. Here, we demonstrate that CD40 cross-linking alone is not sufficient to induce IL-12 production by DC in vivo. Indeed, resting DC make neither the IL-12 p35 nor IL-12 p40 subunits and express only low levels of CD40. Nevertheless, after DC activation by microbial stimuli that primarily upregulate IL-12 p40 and augment CD40 expression, CD40 ligation induces a significant increase in IL-12 p35 and IL-12 p70 heterodimer production. Similarly, IL-12 p70 is produced during T cell activation in the presence but not in the absence of microbial stimuli. Thus, production of bioactive IL-12 by DC can be amplified by T cell-derived signals but must be initiated by innate signals.

关键词： 3T3细胞佐剂免疫/投药和剂量佐剂免疫/生理学抗体单克隆/投药和剂量抗原原虫/投药和剂量抗原原虫/免疫学细胞培养的树突细胞/细胞学树突细胞/免疫学树突细胞/代谢树突细胞/寄生虫学二聚作用注射腹腔内注射静脉内白细胞介素12/生物合成白细胞介素12/代谢分裂间期/免疫学小鼠近交BALBC 小鼠近交C57BL 小鼠近交CBA 小鼠 SCID 小鼠转基因信号传导/免疫学 T淋巴细胞/免疫学弓形虫属/免疫学增量调节/免疫学动物女(雌)性男(雄)性小鼠

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In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation

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BLOOD 2000年第7期96卷 2419-2425页

作者： Kottaridis, PD Milligan, DW Chopra, R Chakraverty, RK Chakrabarti, S Robinson, S Peggs, K Verfuerth, S Pettengell, R Marsh, JCW Schey, S Mahendra, P Morgan, GJ Hale, G Waldmann, H de Elvira, MCR Williams, CD Devereux, S Linch, DC Goldstone, AH Mackinnon, S UCL Hosp Dept Hematol London WC1E 6H England Birmingham Heartlands Hosp Dept Hematol Birmingham B9 5ST W Midlands England Christie Hosp Dept Hematol Manchester Lancs England Univ London St Georges Hosp Dept Hematol London England Guys Hosp Dept Hematol London SE1 9RT England Queen Elizabeth Hosp Dept Hematol Birmingham B15 2TH W Midlands England Leeds Gen Infirm Dept Hematol Leeds W Yorkshire England Univ Oxford Therapeut Antibody Ctr Dept Hematol Oxford England

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4;fludarabine, 30 mg/m(2) on days -7 to -3;and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of non-relapse mortality was 11%. Although longer follow-up is needed to establish the longterm remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD. (Blood. 2000;96:2419-2425) (C) 2000 by The American Society of Hematology.

关键词：抗体单克隆/投药和剂量抗体单克隆/治疗应用抗体肿瘤/投药和剂量抗体肿瘤/治疗应用抗肿瘤药/治疗应用环孢菌素/治疗应用药物疗法联合移植物抗宿主病/预防和控制粒细胞集落刺激因子/投药和剂量粒细胞集落刺激因子/治疗应用血液肿瘤/死亡率血液肿瘤/治疗造血干细胞移植组织相容性试验免疫抑制剂/治疗应用美法仑/投药和剂量甲氨蝶呤/治疗应用微卫星重复核型家庭聚合酶链反应复发移植嵌合体移植预处理/方法治疗结果阿糖腺苷/投药和剂量阿糖腺苷/类似物和衍生物青少年成年人女(雌)性人类男(雄)性中年人

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Pressure delivery of AS-ICAM-1 ODN with LFA-1 mAb reduces reperfusion injury in cardiac allografts

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ANNALS OF THORACIC SURGERY 1999年第1期68卷 119-124页

作者： Feeley, BT Park, AK Alexopoulos, S Hoyt, EG Ennen, MP Poston, RS Robbins, RC Stanford Univ Sch Med Dept Cardiothorac Surg Stanford CA 94305 USA

Background. The goal of this study is to determine the effects of ex vivo hyperbaric pressure administration of AS-ICAM-1 ODN and systemic anti-LFA-1 mAb treatment on reperfusion injury in the rat cardiac allograft model. Methods, A PVG to ACI functional heterotopic rat heart model was used. Donor hearts were treated with either saline or AS-ICAM-1 ODN and 5 atm of hyperbaric pressure for 45 minutes. Anti-LFA-1 mAb was administered systemically prior to reperfusion of the allograft. Allografts were procured 24 hours after transplantation for assessment of reperfusion injury or 72 hours to determine ICAM-1 protein expression. Results. Ex vivo administration of AS-ICAM-1 ODN led to decreases in percentage wet weight (77.1 +/- 0.83% vs 78.7 +/- 1.0%, p < 0.05), myeloperoxidase activity (3.14 +/- 0.72 vs 4.07 +/- 0.59, p < 0.05), contraction band necrosis (6.4 +/- 6.47% vs 21.1 +/- 7.43%, p < 0.01), and ICAM-1 protein expression determined by immunohistochemistry compared to saline controls. Treatment with anti-LFA-1 mAb resulted in decreases in wet weight ratio (76.7 +/- 0.63%, p < 0.05 vs saline), myeloperoxidase activity (3.58 +/- 0.39, p < 0.05 vs saline) and contraction band necrosis (11.8 +/- 3.56%, p < 0.05 vs saline). Combination of pressure administration of AS-ICAM-1 ODN and anti-LFA-1 mAb decreased wet weight ratios (77.1 +/- 0.93%, p < 0.05 vs saline), myeloperoxidase activity (2.88 +/- 0.44, p < 0.01 vs saline), and contraction band necrosis (6.75 +/- 5.67%, p < 0.05 vs saline). Conclusions. Ex vivo pressure mediated delivery of AS-ICAM-1 ODN decreases ICAM-1 protein expression, reduces reperfusion injury in rodent cardiac allografts, and is more effective than anti-LFA-1 mAb treatment alone. (C) 1999 by The Society of Thoracic Surgeons.

关键词：抗体单克隆/投药和剂量大气压心脏移植胞间黏附分子1/分析淋巴细胞功能相关抗原1/免疫学心肌再灌注损伤/代谢心肌再灌注损伤/病理学心肌再灌注损伤/预防和控制心肌/代谢心肌/病理学坏死寡脱氧核糖核苷酸类反义/投药和剂量过氧化物酶/代谢大鼠近交ACI 大鼠近交系移植异位动物男(雄)性大鼠

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Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation

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BLOOD 2000年第7期95卷 2434-2439页

作者： Tsukada, N Akiba, H Kobata, T Aizawa, Y Yagita, H Okumura, K Dokkyo Univ Sch Med Inst Med Sci Div Immunol Mibu Tochigi 3210293 Japan Juntendo Univ Sch Med Dept Immunol Tokyo 113 Japan Niigata Univ Sch Med Dept Internal Med 1 Niigata Japan JST CREST Tokyo Japan

Expression of CD134 (OX40) on activated CD4(+) T cells has been observed in acute graft-versus-host disease (GVHD) after human and rat allogeneic bone marrow transplantation (BMT). We investigated the role of interaction between CD134 and CD134 ligand (CD134L) in a murine model of acute GVHD by using a newly established monoclonal antibody (mAb) against murine CD134L, Acute GVHD was induced by transfer of bone marrow cells and spleen cells into lethally irradiated recipients in a parent (C57BL/6) to first filial generation (C57BL/6 crossed with DBA/2) BMT, Administration of anti-CD134L mAb significantly reduced the lethality of acute GVHD and other manifestations of the disease, such as loss of body weight, hunched posture, diarrhea, and patchy alopecia. The survival rate 80 days after BMT in mice treated with the mAb was about 70%, whereas all mice treated with control antibodies died within 43 days. Histologic examinations revealed that inflammatory changes in target organs such as the liver, gut, and skin were also ameliorated in mice treated with the mAb compared with control mice. An in vitro assay of T-cell proliferation showed a marked hyporesponsiveness to host alloantigen In samples from mice treated with anti-CD134L mAb, In addition, low levels of interferon gamma and transiently elevated levels of interleukin 4 and IgE in serum samples were found in mice treated with anti-CD134L mAb, These results suggest that CD134-CD134L interactions have an important role in the pathogenesis of acute GVHD, (Blood, 2000;95:2434-2439) (C) 2000 by The American Society of Hematology.

关键词：急性病抗体单克隆/投药和剂量抗原 CD27/免疫学骨髓移植细胞因子类/血液移植物抗宿主病/免疫学移植物抗宿主病/病理学移植物抗宿主病/预防和控制免疫球蛋白E/血液同种抗原/免疫学淋巴细胞培养试验混合小鼠近交C3H 小鼠近交C57BL 小鼠近交DBA 受体 OX40 受体肿瘤坏死因子脾/移植动物女(雌)性小鼠大鼠

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Synergy between intracoronary stenting and abciximab improving angiographic and clinical outcomes of primary angioplasty in acute myocardial infarction

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第3期86卷 269-274页

作者： Giri, S Mitchel, JF Hirst, JA McKay, RG Azar, RR Mennett, R Waters, DD Kiernan, FJ Hartford Hosp Cardiac Catheterizat Lab Div Cardiol Hartford CT 06102 USA Univ Connecticut Sch Med Farmington CT USA San Francisco Gen Hosp Div Cardiol San Francisco CA 94110 USA Univ Calif San Francisco San Francisco CA 94143 USA

This study examined 650 consecutive patients who presented with an acute myocardial infarction and were treated with primary angioplasty within 12 hours of symptom onset between August 1995 and December 1998. Patients were placed into 4 treatment groups depending on the adjunctive therapy they received: group 1, percutaneous transluminal coronary angioplasty (PTCA) ("balloon PTCA alone";n = 220);group 2, PTCA plus intracoronary stent placement ("stent";n 128);group 3, PTCA plus abciximab therapy ("abciximab";n 104);and group 4, PTCA plus intracoronary stent placement plus abciximab therapy ("steni/abciximab";n = 198). The patients' clinical characteristics, severity of disease, and total ischemia time on presentation were similar. At baseline, abciximab and stent/abciximab groups had a higher incidence of thrombus on coronary angiography. Postprocedural quantitative coronary analysis showed a significantly larger minimum luminal diameter in the stent and stent/abciximab groups than PTCA alone. Overall, stents were most efficacious in reducing target vessel revascularization rate, whereas abciximab was associated with a higher postprocedural Thrombolysis In Myocardial Infarction-3 trial flow and less "no reflow." The best angiographic result was achieved in the stent/abciximab group. Similarly, the primary combined end point of death, myocardial infarction, and target vessel revascularization at 30 days was the lowest (6.1%) in the stent/abciximab group. The combination of abciximab and stenting in primary angioplasty for acute myocardial infarction is thus synergistic and is associated with improved angiographic and clinical results at 30-day follow-up. (C) 2000 by Excerpta Medico, Inc.

关键词：抗体单克隆/投药和剂量综合疗法冠状血管造影术随访研究免疫球蛋白Fab片段/投药和剂量心肌梗死/死亡率心肌梗死/放射摄影术心肌梗死/治疗血小板聚集抑制剂/投药和剂量回顾性研究支架存活率治疗结果老年人女(雌)性人类男(雄)性中年人

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Reduced thrombus burden with abciximab delivered locally before percutaneous intervention saphenous vein grafts

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AMERICAN HEART JOURNAL 2000年第5期139卷 824-829页

作者： Barsness, GW Buller, C Ohman, M Schechter, E Pucillo, A Taylor, MA Miller, MJ Reiner, JS Churchill, D Chandler, AB Gonzalez, M Smith, J Tommaso, C Berdan, LG Wildermann, NM Hasdai, D Holmes, DR Mayo Clin Rochester MN 55905 USA Duke Clin Res Inst Durham NC USA Vancouver Gen Hosp Vancouver BC Canada Vet Adm Med Ctr Oklahoma City OK 73104 USA Westchester Cty Med Ctr Valhalla NY 10595 USA Deborah Heart & Lung Ctr Browns Mills NJ USA Pitt Cty Hosp Greenville NC USA George Washington Univ Med Ctr Washington DC 20037 USA Washington Reg Med Ctr Fayetteville AR USA Univ Hosp Augusta GA USA Columbia Pk Med Ctr Orlando FL USA Florida Heart & Vasc Inst Tampa FL USA Rush N Shore Hosp Skokie IL USA Mayo Clin Rochester MN USA

Background Existing thrombus can complicate percutaneous saphenous vein graft (SVG) intervention. Local delivery of thrombolytics has been used to reduce the thrombus burden often associated with these interventions. We sought to determine whether local delivery of a platelet glycoprotein IIb/IIIa inhibitor is feasible and can reduce thrombus burden before percutaneous SVG intervention. Methods We performed a multicenter pilot study of abciximab (0.25 mg/kg) given by local delivery catheter before percutaneous intervention for de novo SVG stenoses followed by intravenous infusion. All patients (n = 58) had greater than or equal to 60% stenosis and Thrombolysis In Myocardial Infarction (TIMI) grade >0 flow in an SVG of 3 to 4 mm in diameter. Percent diameter stenosis, TIMI thrombus grade, and TIMI flow grade were measured before and after delivery of abciximab and after intervention. Results Median percent diameter stenosis improved from 69% to 45% (P = .0001) after local delivery, and TIMI thrombus grade greater than or equal to 1 incidence reduced from 68% to 34% (P = .0001). TIMI flow grade was not significantly affected (P = .12). All patients had a successful intervention (less than or equal to 50% residual stenosis). Conclusions Local abciximab delivery before percutaneous SVG intervention is associated with significantly reduced thrombus burden, significantly improved percent diameter stenosis, and excellent acute procedural results. Further studies of this approach are warranted to define its clinical utility.

关键词：抗体单克隆/投药和剂量冠状血管造影术/药物作用冠状动脉分流术冠状动脉血栓形成/药物疗法冠状动脉血栓形成/放射摄影术移植物闭塞血管/药物疗法移植物闭塞血管/放射摄影术免疫球蛋白Fab片段/投药和剂量输注泵试点项目血小板聚集抑制剂/投药和剂量血小板糖蛋白GPⅡb-Ⅲa复合物/拮抗剂和抑制剂术前用药法支架治疗结果静脉/移植老年人女(雌)性人类男(雄)性中年人

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Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice

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BLOOD 2000年第7期96卷 2520-2527页

作者： Nieswandt, B Bergmeier, W Rackebrandt, K Gessner, JE Zirngibl, H Univ Witten Herdecke Klinikum Wuppertal IMMI Dept Mol Oncol D-42283 Wuppertal Germany Hannover Med Sch Dept Clin Immunol D-3000 Hannover Germany

The pathogenic effects of antiplatelet antibodies were investigated in mice, Monoclonal antibodies (mAbs) of different immunoglobulin G subclass directed against mouse GPIIbIIIa, GPIIIa, GPIb alpha, GPIb-IX, GPV, and CD31 were generated and characterized biochemically. MAbs against GPIb-IX, GPV, CD31, and linear epitopes on GPIIIa had mild and transient effects on platelet counts and induced no spontaneous bleeding, Anti-GPIb alpha mAbs induced profound irreversible thrombocytopenia(< 3% of normal) by Fc-independent mechanisms but only had minor effects on hematocrits. In contrast, injection of intact mAbs, but not F(ab)(2) fragments, against conformational epitopes on GPIIbIIIa, induced irreversible thrombocytopenia, acute systemic reactions, hypothermia, decreased hematocrits, and a paradoxical loss of surface GPIIbIIIa on platelets in vivo, the latter suggesting the formation of platelet-derived microparticles, Blockage of platelet-activating factor receptors inhibited the acute reactions, but not thrombocytopenia, loss of GPIIbIIIa, and decreases in hematocrits. Repeated injections of low doses of anti-GPIIbIIIa antibodies resulted in profound thrombocytopenia and bleeding, whereas no acute systemic reactions were observed. These data strongly suggest that the identity of the target antigen recognized by antiplatelet antibodies determines the mechanisms of platelet destruction and the severity of bleeding in mice, the latter depending on previously unrecognized anti-GPIIbIIIa-specific inflammatory mechanisms, (Blood, 2000;96: 2520-2527) (C) 2000 by The American Society of Hematology.

关键词：抗体单克隆/投药和剂量抗体单克隆/药理学抗原 CD31/免疫学自身抗原/免疫学血小板/化学血小板/免疫学表位出血/免疫学免疫球蛋白Fc片断/免疫学免疫球蛋白Fc片断/药理学免疫球蛋白G/药理学表型血小板活化因子/药理学血小板糖蛋白GPⅡb-Ⅲa复合物/免疫学血小板糖蛋白GPⅠb-Ⅸ复合物/免疫学紫癜血小板减少性特发性/免疫学无特异性病原体有机物动物小鼠

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Survival of destrobilated adults of Taenia crassiceps in T-cell-depleted Mongolian gerbils

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PARASITOLOGY RESEARCH 2000年第4期86卷 284-289页

作者： Sato, H Ihama, Y Kamiya, H Hirosaki Univ Sch Med Dept Parasitol Hirosaki Aomori 0368562 Japan

In Mongolian gerbils (Meriones unguiculatus), prednisolone treatment induces the survival of strobilated Taenia crassiceps to sexual maturity followed by fecal release of gravid proglottides. The mechanism underlying the effects of prednisolone has not been elucidated in this taeniid/rodent model. Using a novel murine monoclonal antibody specific to a cell-surface determinant of gerbil T-cells (HUSM-M.g.15 of IgG(2b) isotype) for in vivo depletion of the cells, we examined the T-cell dependence of the following two phenomena: (1) elimination of strobilated T. crassiceps from the intestine of naive gerbils, and (2) depressed egg formation by the cestode in prednisolone-treated gerbils. In T-cell-depleted gerbils, only destrobilated adults were recovered from the intestine, although the recovery rate was comparable with that observed in prednisolone-treated animals. Egg formation by the cestode in T-cell-depleted, prednisone-treated gerbils did not differ from that seen in gerbils treated with prednisolone alone. We conclude that one of main effects of prednisolone can be ascribed to the suppression of T-cell functions that work to eliminate strobilated T. crassiceps from gerbils.

关键词：抗体单克隆/投药和剂量伴刀豆球蛋白A/药理学囊尾蚴/生理学沙鼠亚科/免疫学糖皮质激素类/药理学免疫球蛋白同型/免疫学免疫组织化学肠/寄生虫学淋巴细胞去除术小鼠近交BALBC 寄生虫虫卵计数泼尼松龙/类似物和衍生物泼尼松龙/药理学脾/细胞学脾/免疫学 T淋巴细胞/药物作用 T淋巴细胞/免疫学动物男(雄)性小鼠

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Repeated infusions of infliximab, a chimeric anti-TNFα monoclonal antibody, in patients with active spondyloarthropathy:: one year follow up

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ANNALS OF THE RHEUMATIC DISEASES 2002年第3期61卷 207-212页

作者： Kruithof, E Van den Bosch, F Baeten, D Herssens, A De Keyser, F Mielants, H Veys, EM Ghent Univ Hosp Dept Rheumatol B-9000 Ghent Belgium

Background: In a pilot study, the anti-tumour necrosis factor a monoclonal antibody, infliximab, induced a rapid and significant improvement in global, peripheral, and axial disease manifestations of patients with active spondyloarthropathy. Objective: To determine whether repeated infusions of infliximab would effectively and safely maintain the observed effect. Methods: Safety and efficacy of a maintenance regimen (5 mg/kg infliximab every 14 weeks) was evaluated using the measurements reported in the pilot study. Of the 21 patients, 19 completed the one year follow up for efficacy;two patients changed to another dosing regimen after week 12 owing to partial lack of efficacy. However, they are still being followed up for safety analysis. Results: After each re-treatment a sustained significant decrease of all disease manifestations was observed. Before re-treatment, symptoms recurred in 3/19 (16%) at week 20, in 13/19 (68%) at week 34 and in 15/19 (79%) at week 48. No withdrawals due to adverse events occurred. Twelve minor infectious episodes were observed. Twelve patients (57%) developed antinuclear antibodies;in four of them (19%) anti-dsDNA antibodies were detected. However, no lupus-like symptoms occurred. Conclusion: In this open study of infliximab in patients with active spondyloarthropathy, the significant improvement of all disease manifestations was maintained over a one year follow up period without major adverse events. Although recurrence of symptoms was noted in a rising number of patients before each re-treatment, no loss of efficacy was observed after re-treatment.

关键词：抗体抗核/免疫学抗体单克隆/投药和剂量抗风湿药/投药和剂量荧光抗体技术间接随访研究试点项目再治疗椎关节病变/药物疗法椎关节病变/免疫学统计学非参数治疗结果成年人老年人女(雌)性人类男(雄)性中年人

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Clinical correlates and course of thrombocytopenia during percutaneous coronary intervention in the era of abciximab platelet glycoprotein IIb/IIIa blockade

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AMERICAN HEART JOURNAL 2000年第1期140卷 74-+页

作者： Kereiakes, DJ Berkowitz, SD Lincoff, AM Tcheng, JE Wolski, K Achenbach, R Melsheimer, R Anderson, K Califf, RM Topol, EJ Carl & Edyth Lindner Ctr Res & Educ Cincinnati OH 45219 USA Ohio Heart Hlth Ctr Cincinnati OH USA Univ Cincinnati Coll Med Cincinnati OH USA Duke Univ Med Ctr Dept Med Div Hematol Coagulat Durham NC 27710 USA Duke Univ Med Ctr Dept Med Div Cardiol Durham NC 27710 USA Cleveland Clin Fdn Cleveland OH 44195 USA Centocor Inc Malvern PA 19355 USA

Background Thrombocytopenia is infrequently associated with abciximab therapy but may contribute to hemorrhagic risk. Factors associated with development of thrombocytopenia, the role of weight-adjustment in concomitant heparin administration, and clinical outcomes in patients with thrombocytopenia are not well defined. Methods and Results Pooled data from 3 placebo-controlled, randomized trials (EPIC, EPILOG, and EPISTENT) of abciximab therapy during percutaneous coronary intervention identified 178 patients (2.4% of 7290 patients) in whom thrombocytopenia (platelet count <100 x 10(9)/L) developed after enrollment. Multivariate regression analysis identified age (>65 years;P < .001), weight (<90 kg;P = .023), baseline platelet count (<200 x 10(9)/L;P < .001), abciximab therapy (P = .002), and enrollment into the EPIC trial (P < .001) to be associated with development of thrombocytopenia. Major and minor nonsurgical hemorrhage and transfusion were more frequent (all P < .001) in thrombocytopenic patients. Although the primary composite clinical end point of these trials (death, myocardial infarction, or urgent revascularization to 30 days) was observed with similar frequency in patients with (11.2%) and those without (7.9%;P = .114) thrombocytopenia, 30-day mortality rate was higher in thrombocytopenic patients (8.4% vs 0.6%, respectively;P < .001). This excess mortality rate persisted after excluding patients in whom thrombocytopenia was first noted after the performance of coronary bypass surgery (4.8% vs 0.6%;P < .001). Among patients in whom thrombocytopenia developed during these trials, those who received prophylactic abciximab had fewer primary end point events (7.1% vs 23.1%;P = .056) and had a lower 30-day mortality rate (3.5% vs 15.4%;P = .048) than patients with thrombocytopenia who had received prophylactic placebo. Conclusions Thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention was more Frequent in older, lighter-we

关键词：年龄分布抗体单克隆/投药和剂量置信区间疾病恶化免疫球蛋白Fab片段/投药和剂量发病率注射皮下 Logistic模型多元分析心肌梗死/治疗比值比血小板聚集抑制剂/投药和剂量概率危险因素性别分布存活率血小板减少/化学诱导血小板减少/流行病学血小板减少/病理生理学老年人女(雌)性人类男(雄)性中年人

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