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世界核心医学期刊文摘（心脏病学分册） 2005年第2期1卷 28-29页

作者： kovacs M.J. Kearon C. Rodger M. 王永兴 kovacs London Health Sciences Centre 800 Commissioners Rd E London Ont. N6A 4G5 Canada Dr.

Background When warfarin is interrupted for surgery, low molecular weight h eparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the ef ficacy and safety of bridging therapy with low molecular weight heparin initia ted out of hospital. Methods and Results This was a prospective, multicenter, s ingle arm cohort study of patients at high risk of arterial embolism (prostheti c valves and atrial fibrillation with a major risk factor). Warfarin was held fo r 5 days preoperatively. Low molecular weight heparin was given 3 days preoper atively and at least 4 days postoperatively. Patients were followed up for 3 mon ths for thromboembolism and bleeding. Eleven Canadian tertiary care academic cen ters participated; 224 patients were enrolled. Eight patients (3.6%; 95%CI, 1. 8 to 6.9) had an episode of thromboembolism, of which 2(0.9%; 95%CI, 0.2 to 3. 2) were judged to be due to cardioembolism. Of these 8 episodes of thromboemboli sm, 6 occurred in patients who had warfarin deferred or withdrawn because of ble eding. There were 15 episodes of major bleeding(6.7%; 95%CI, 4.1 to 10.8): 8 o ccurred intraoperatively or early postoperatively before low molecular weight heparin was restarted, 5 occurred in the first postoperative week after low mol ecular weight heparin was restarted, and 2 occurred well after low molecular weight heparin was stopped. There were no deaths. Conclusions Bridging therapy with subcutaneous low molecular weight heparin is feasible; however, the optimal approach for the management o f patients who require temporary interruption of warfarin to have invasive proce dures is uncertain.

关键词：低分子肝素动脉栓塞血栓栓塞事件心源性栓塞人工瓣膜外科手术队列研究于术学术中心

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Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

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World Journal of Gastroenterology 2005年第10期11卷 1489-1495页

作者： Peter Laszlo Lakatos Laszlo Lakatos Ferenc Szalay Claudia Willheim-Polli Christoph (O|¨)sterreicher Zsolt Tulassay Tamas Molnar Walter Reinisch Janos Papp Gyula Mozsik Hungarian IBD Study Group Peter Ferenci 1st Department of Medicine Laszlo Lakatos Department of Internal Medicine 4 2nd Department of Medicine Semmelweis University 2nd Department of MedicineSemmelweis UniversityBudapest:Laszlo PronaiAnnamaria NemethPal Miheller Erzsebet Hospital 1st Department of MedicineBudapest: Agota KovacsLaszlo Bene Szent Janos Hospital 1st Department of Medicine:Gyorgy Szekely University of Pecs 1st Department of MedicinePecs:Beata Gasztonyi University of Szeged 1st Department of MedicineSzeged:Ferenc NagyJanos Lonovics Semmelweis Hospital 1st Department of MedicineMiskolc:Laszlo Ujszaszy University of Debrecen 2nd Department of MedicineDebrecen:Istvan AltorjaiKaroly Palatka Kenezi Gy. County Hospital 2nd Department of MedicineDebrecen: Gyula G. Kiss County Hospital 2nd Department of MedicineZalaegerszeg Ferenc Tarnok Markusovszky Hospital2nd Department of MedicineSzombathely:Zoltan Dobronte Csolnoky F. County Hospital 1st Department of MedicineVeszprem:Zsuzsanna ErdelyiTunde PandurGabor Mester

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

关键词： Crohn's disease NOD2 CARD15 TLR4 Extraintestinal manifestation Phenotype

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