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Heparins in diabetic microangiopathy: rationale and preliminary clinical results. 肝素治疗糖尿病微血管病变:基本原理和初步临床结果。
Pub Date : 1999-12-01 DOI: 10.1159/000054113
F J van Der Woude

It has been postulated, based upon epidemiological data, that genetic differences in the enzymes involved in the sulphation of glycosaminoglycan (GAG) side-chains of heparan sulphate (HS) proteoglycans are of crucial importance in the pathogenesis of diabetic nephropathy. An alteration in GAG metabolism is also believed to be responsible for the well-known co-occurrence of diabetic nephropathy and extrarenal micro- and macroangiopathy. In this article, recent in-vitro and in-vivo studies on the role of HS-GAG in the pathogenesis of diabetic nephropathy are discussed. Preliminary data suggest that HS-GAG treatment may be of benefit in patients with insulin-dependent diabetes mellitus, nephropathy and retinopathy. Results in patients with non-insulin-dependent diabetes mellitus are less convincing, although not completely negative.

根据流行病学数据,已经假设参与硫酸肝素(HS)蛋白聚糖侧链糖胺聚糖(GAG)磺化的酶的遗传差异在糖尿病肾病的发病机制中起着至关重要的作用。GAG代谢的改变也被认为是众所周知的糖尿病肾病和肾外微血管和大血管病变共同发生的原因。本文就HS-GAG在糖尿病肾病发病机制中的体外和体内研究进展进行综述。初步数据表明HS-GAG治疗可能对胰岛素依赖型糖尿病、肾病和视网膜病变患者有益。非胰岛素依赖型糖尿病患者的结果不太令人信服,尽管不是完全阴性。
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引用次数: 5
Use of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes undergoing coronary revascularization. 糖蛋白IIb/IIIa抑制剂在接受冠状动脉血管重建术的急性冠状动脉综合征患者中的应用
Pub Date : 1999-12-01 DOI: 10.1159/000054115
J J Popma

This paper briefly reviews the results from three recent large-scale clinical trials evaluating the benefit of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes (ACS). The available data suggest that these are promising agents for the management of ACS, particularly in improving the immediate outcome in the acute setting.

本文简要回顾了最近三项大规模临床试验的结果,这些试验评估了糖蛋白IIb/IIIa抑制剂对急性冠脉综合征(ACS)患者的益处。现有的数据表明,这些都是治疗ACS的有希望的药物,特别是在改善急性情况下的直接结果。
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引用次数: 0
Should patients with venous thromboembolism and cancer be treated differently? 静脉血栓栓塞和癌症患者应该区别对待吗?
Pub Date : 1999-12-01 DOI: 10.1159/000054122
S M Smorenburg, B A Hutten, M H Prins

Patients with malignant disease constitute a significant subgroup among patients with venous thromboembolism. Current results suggest that cancer patients are not only at an increased risk for thromboembolic events, particularly during chemotherapy treatment or after surgery, they also have an increased risk for bleeding complications while receiving oral anticoagulant treatment. The exact incidences of venous thromboembolic complications for the various types of cancer, however, are not well determined. Recent studies have indicated that subcutaneous low-molecular-weight heparin (LMWH) is as safe and effective as intravenous unfractionated heparin (UFH) in the initial treatment of venous thromboembolism. Moreover, a meta-analysis has provided preliminary evidence that, compared with UFH, LMWH treatment may prolong survival in cancer patients. Initiation of LMWH treatment in these patients is, therefore, recommended. Prospective randomized clinical trials to assess the optimum dose and duration of therapy are called for.

在静脉血栓栓塞患者中,恶性疾病患者是一个重要的亚群。目前的研究结果表明,癌症患者不仅在化疗期间或手术后发生血栓栓塞事件的风险增加,而且在接受口服抗凝治疗时出血并发症的风险也增加。然而,各种类型癌症的静脉血栓栓塞并发症的确切发生率尚不清楚。最近的研究表明,在静脉血栓栓塞的初始治疗中,皮下低分子肝素(LMWH)与静脉未分离肝素(UFH)一样安全有效。此外,一项荟萃分析提供了初步证据,表明与UFH相比,低分子肝素治疗可以延长癌症患者的生存期。因此,建议这些患者开始低分子肝素治疗。需要前瞻性随机临床试验来评估最佳剂量和治疗持续时间。
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引用次数: 20
Modern approach to diagnosis in patients with suspected deep vein thrombosis. 疑似深静脉血栓形成的现代诊断方法。
Pub Date : 1999-12-01 DOI: 10.1159/000054107
P S Wells, D R Anderson

Deep vein thrombosis is a relatively common disease, amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with the non-invasive imaging procedure ultrasonography, but limitations exist. As with all tests, there is a potential for false-positive and false-negative results. The latter are especially an issue for calf vein thrombi, and this in part has led to the concept of serial testing of the proximal venous system rather than imaging the calf. The premise of the repeat (serial) test is that only thrombi that extend to the proximal system are clinically relevant and such thrombi will be detected on the repeat test. However, despite the safety of the serial-testing concept, it is inconvenient and expensive. In the last few years, the diagnostic process has been improved by the validation of a clinical model that accurately categorizes patients as having low, moderate or high probability of deep vein thrombosis. Among the improvements this provides is the elimination of serial testing if the ultrasound is normal and the clinical probability low. The fibrin degradation product D-dimer has been demonstrated to have a high negative predictive value and has also proven useful in diagnostic algorithms. The combination of the D-dimer with clinical model assessment will enable diagnostic-testing strategies that are more safe, effective and convenient for patients.

深静脉血栓形成是一种相对常见的疾病,可以治疗,但如果不治疗,可能会导致致命的后果。大多数患者可以通过无创超声检查诊断,但存在局限性。与所有测试一样,有可能出现假阳性和假阴性结果。后者对于小腿静脉血栓尤其是个问题,这在一定程度上导致了对近端静脉系统进行系列检测的概念,而不是对小腿进行成像。重复(系列)试验的前提是只有延伸到近端系统的血栓才具有临床相关性,重复试验才会检测到这种血栓。然而,尽管串行测试的概念是安全的,它是不方便和昂贵的。在过去的几年里,通过临床模型的验证,诊断过程得到了改进,该模型可以准确地将患者分为深静脉血栓形成的低、中、高概率。其中的改进是,如果超声是正常的,临床概率低,消除了一系列的测试。纤维蛋白降解产物d -二聚体已被证明具有很高的阴性预测值,并且已被证明在诊断算法中有用。d -二聚体与临床模型评估的结合将使诊断测试策略对患者更安全、有效和方便。
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引用次数: 8
Low-molecular-weight heparins in acute unstable coronary artery disease - an update. 低分子肝素在急性不稳定冠状动脉疾病中的作用
Pub Date : 1999-12-01 DOI: 10.1159/000054116
A G Turpie

Low-molecular-weight heparins (LMWHs) have been rigorously evaluated in the management of acute coronary ischaemia. The results of clinical trials suggest that the LMWHs (enoxaparin, dalteparin and nadroparin) are effective and safe in the treatment of unstable angina and non-Q-wave myocardial infarction. Two studies have shown enoxaparin to be more effective than unfractionated heparin in this setting. Furthermore, the pharmacologic and pharmacokinetic characteristics of LMWHs result in them having practical and economic advantages. Data on the benefits of long-term therapy with LMWHs are conflicting.

低分子肝素(LMWHs)在急性冠状动脉缺血的治疗中得到了严格的评价。临床试验结果表明,低分子肝素(依诺肝素、达尔特帕林和纳罗帕林)治疗不稳定型心绞痛和非q波型心肌梗死是有效和安全的。两项研究表明,在这种情况下,依诺肝素比未分离肝素更有效。此外,低分子肝素的药理学和药代动力学特性使其具有实用和经济优势。关于低分子白细胞长期治疗的益处的数据是相互矛盾的。
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引用次数: 5
Venous thrombosis: prevalence and interaction of risk factors. 静脉血栓形成:患病率和危险因素的相互作用。
Pub Date : 1999-12-01 DOI: 10.1159/000054106
F R Rosendaal

The key to understanding why certain individuals develop deep vein thrombosis at varying times, despite similar risk factors being present, is the realization of the importance of gene-gene and gene-environment interactions between risk factors. The discovery of factor V Leiden and several other coagulation abnormalities, which are now known to be common in the general population, has revolutionized the way in which the aetiology of venous thrombosis is viewed. On the basis of current knowledge, time-dependent models taking account of various forms of interaction have been developed.

尽管存在相似的危险因素,但理解为什么某些个体在不同时间发生深静脉血栓的关键是认识到危险因素之间基因-基因和基因-环境相互作用的重要性。因子V Leiden和其他几种凝血异常的发现,现在已知在一般人群中是常见的,已经彻底改变了静脉血栓形成的病因学。在现有知识的基础上,考虑到各种形式的相互作用的时间依赖模型已经被开发出来。
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引用次数: 46
For how long should the treatment with vitamin K antagonists be maintained? 维生素K拮抗剂治疗应该维持多久?
Pub Date : 1999-12-01 DOI: 10.1159/000054121
S Schulman

Studies have shown that in most patients with venous thromboembolism (VTE), continuation of treatment with vitamin K antagonists for up to 27 months significantly reduces the probability of recurrence. Likewise, prolongation of oral anticoagulation beyond 6 months is believed to be of benefit in patients with certain forms of hereditary thrombophilia. Very prolonged periods of treatment with vitamin K antagonists at standard doses, although conferring benefit regarding the risk of recurrence of VTE, are associated with an increased incidence of major bleeds and require intensive monitoring. Use of a lower intensity of anticoagulation may reduce these negative aspects and enable anticoagulation to be carried out for longer.

研究表明,在大多数静脉血栓栓塞(VTE)患者中,持续使用维生素K拮抗剂治疗长达27个月可显著降低复发的可能性。同样,延长口服抗凝治疗超过6个月被认为对某些形式的遗传性血栓患者有益。标准剂量的维生素K拮抗剂治疗时间过长,虽然对静脉血栓栓塞复发风险有好处,但与大出血发生率增加有关,需要密切监测。使用较低强度的抗凝治疗可以减少这些负面影响,使抗凝治疗能够进行更长时间。
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引用次数: 2
Modern strategy for diagnosis and treatment of pulmonary embolism. 肺栓塞诊断与治疗的现代策略。
Pub Date : 1999-12-01 DOI: 10.1159/000054108
J P Laaban

Various techniques are available for the diagnosis of pulmonary embolism (PE), including pulmonary angiography, perfusion-ventilation lung scanning, D-dimer measurement, venous ultrasonography and, most recently, helical computerized tomography of the chest. The advantages and disadvantages of these techniques, used alone or in combination, are briefly discussed. Studies have indicated that treatment with low-molecular-weight heparin (LMWH), as well as being more convenient to administer, is as safe and effective as standard heparin therapy in acute PE. However, the efficacy and safety of LMWH in patients with acute PE and haemodynamic instability requires verification. Finally, the indications of inferior vena caval filters and thrombolytic therapy are outlined.

肺栓塞(PE)的诊断有多种技术,包括肺血管造影、肺灌注通气扫描、d -二聚体测量、静脉超声检查以及最近的胸部螺旋计算机断层扫描。简要讨论了这些技术单独使用或组合使用的优点和缺点。研究表明,在急性PE治疗中,低分子肝素(LMWH)治疗与标准肝素治疗一样安全有效,而且给药更方便。然而,低分子肝素在急性PE伴血流动力学不稳定患者中的有效性和安全性有待验证。最后,概述了下腔静脉滤过器和溶栓治疗的适应症。
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引用次数: 1
Extended prophylaxis against venous thromboembolism following total hip and knee replacement. 全髋关节和膝关节置换术后静脉血栓栓塞的扩展预防。
Pub Date : 1999-12-01 DOI: 10.1159/000054109
R D Hull, G F Pineo

The recently reported reductions in the incidence of post-operative venous thromboembolism (VTE) are related to the widespread use of prophylactic anticoagulants. Many uncertainties remain with regard to the most effective ways to use thromboprophylaxis, however. The trend towards shorter hospital stays means that patients may receive less than the recommended 7-10 days of prophylaxis. Prolonged periods of thromboprophylaxis may be beneficial for patients at high risk of post-operative VTE, such as those undergoing major orthopaedic surgery. The relative rarity of symptomatic deep vein thrombosis and pulmonary embolism means that very large patient populations are required for studies that rely on clinical endpoints, but studies using venographic endpoints have shown 28-35 days of prophylaxis with low-molecular-weight heparin to be more effective than 10-14 days. Other factors that may influence the efficacy of thromboprophylaxis include the timing of the first injection and the choice of agent.

最近报道的术后静脉血栓栓塞(VTE)发生率的降低与预防性抗凝剂的广泛使用有关。然而,关于使用血栓预防的最有效方法仍有许多不确定因素。住院时间缩短的趋势意味着患者接受的预防治疗可能少于建议的7-10天。长时间的血栓预防可能对术后静脉血栓栓塞风险高的患者有益,例如那些接受大型骨科手术的患者。症状性深静脉血栓和肺栓塞的相对罕见意味着依赖临床终点的研究需要非常大的患者群体,但使用静脉造影终点的研究表明,28-35天的低分子肝素预防比10-14天更有效。其他可能影响血栓预防疗效的因素包括第一次注射的时间和药物的选择。
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引用次数: 21
Comparative inhibition of LPS-activated human monocyte-induced thrombin generation by unfractionated heparin and low molecular weight heparins. 未分离肝素和低分子量肝素对lps激活的人单核细胞诱导凝血酶生成的比较抑制作用。
Pub Date : 1999-11-01 DOI: 10.1159/000022517
P Nguyên, M G Rémy, G Potron

Monocyte tissue factor may play a role in the physiological or pathological triggering of blood coagulation. It is well known that unfractionated heparin and low molecular weight heparins inhibit extrinsic thrombin generation. However, this notion has never been confirmed in a physiological model using tissue factor obtained from stimulated human monocytes. This is the purpose of this study. It was important to obtain a pure preparation of monocytes with no platelet contamination. This was possible by leukapheresis and elutriation. Under sterile and endotoxin-free conditions, the process does not activate tissue factor expression by monocytes. We adapted the technique of thrombin generation on an automatic analyzer and used human monocyte tissue factor to trigger thrombin generation. Our results show that unfractionated and low molecular weight heparins potently inhibit monocytic tissue factor induced thrombin generation. The comparison of low molecular weight heparins suggests that molecules with higher anti-IIa/anti-Xa ratios exert a stronger inhibitory effect. These data may be relevant to explain the therapeutic effects of unfractionated and low molecular weight heparins in cardiovascular disorders such as unstable angina.

单核细胞组织因子可能在凝血的生理或病理触发中起作用。众所周知,未分级肝素和低分子量肝素抑制外源性凝血酶的产生。然而,这一概念从未在使用从受刺激的人单核细胞中获得的组织因子的生理模型中得到证实。这就是本研究的目的。获得一种没有血小板污染的纯单核细胞是很重要的。这可以通过白细胞分离和洗脱。在无菌和无内毒素的条件下,该过程不会激活单核细胞的组织因子表达。我们在自动分析仪上采用凝血酶生成技术,使用人单核细胞组织因子触发凝血酶生成。我们的研究结果表明,未分离的低分子量肝素能有效抑制单核细胞组织因子诱导的凝血酶的产生。低分子量肝素的比较表明,具有较高抗iia /抗xa比值的分子具有更强的抑制作用。这些数据可能与解释未分离肝素和低分子量肝素治疗心血管疾病(如不稳定心绞痛)的疗效有关。
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引用次数: 2
期刊
Haemostasis
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